PMID- 11946425
TI  - in vitro processing of HeLa cell preribosomes by a nucleolar endoribonuclease.

PMID- 11946426
TI  - Primary sequence of glutamic acid tRNA II from Escherichia coli.

PMID- 11946427
TI  - Inhibition of broad spectrum hemagglutinin from Pseudomonas aeruginosa by D
      galactose and its derivatives.

PMID- 11946430
TI  - A method of estimating the magnitude of the light-induced electrical potential
      across the thylakoid membranes.

PMID- 11946429
TI  - Non-ribosomal biosynthesis of linear gramicidins.

PMID- 11946428
TI  - ?
AB  - Fatty acids of acyl steryl glycoside (acyl SG) of different plants producing both
      green and photosynthetically inactive tissue have been analyzed. The major
      components are in all cases 16:0, 18:2 and 18:3 acids. The fatty acid composition
      of acyl SG of green parts is very similar to that of etiolated, pale or storage
      tissue of the same plant. Generally the degree of saturation of acyl SG is higher
      than that of the corresponding total lipid. Acyl SG tends to be more saturated in
      green parts than in colorless tissues of the same plant. Conversely, total lipid
      of green tissue containing large amounts of galactolipids and 18:3 acid is much
      less saturated than that of photosynthetically inactive tissue. Though containing
      smaller amounts of 18:3, and in some cases unsaturated C(16) acids, acyl SG does
      not reflect the drastic increase of these acids in the total lipid of green
      tissue. It is concluded that fatty acids of acyl SG originate mainly from an acyl
      donor other than chloroplast galactolipids.

PMID- 11946431
TI  - On the origin of stereospecificity in biological systems.

PMID- 11946432
TI  - Cell interactions. A report on the 3rd Lepetit Colloquium held at the Royal
      Society of Medicine, London, during 15-17 November, 1971.

PMID- 11946433
TI  - Cyclic nucleotide phosphodiesterase activity in normal mouse pancreatic islets.

PMID- 11946434
TI  - Three-dimensional structure of oligomycin B.

PMID- 11946435
TI  - Genetic control of glucose uptake by Escherichia coli.

PMID- 11946436
TI  - Fluorescence and delayed light emission in Tris-washed chloroplasts.

PMID- 11946437
TI  - Constant and specific proportion groups of enzymes in rat mammary gland and
      adipose tissue in relation to lipogenesis.

PMID- 11946438
TI  - Thyrotropin-releasing hormone receptor: Its partial purification from bovine
      anterior pituitary gland and its close association with adenyl cyclase.

PMID- 11946439
TI  - Association behaviour of rat liver glutamate dehydrogenase.

PMID- 11946440
TI  - The use of immobilised derivatives of urease and urate oxidase in automated
      analysis.

PMID- 11946441
TI  - Kinetic aspects of the irreversible inhibition of trypsin and related enzymes by
      p-[m(m-Fluorosulfonylphenylureido)phenoxyethoxy] benzamidine.

PMID- 11946442
TI  - Synthesis and properties of 8alpha-substituted riboflavins of biological
      importance.

PMID- 11946443
TI  - Isolation of the folate-binding protein from cow's milk by the use of affinity
      chromatography.

PMID- 11946444
TI  - Susceptibility of membrane phospholipids in erythrocyte ghosts to phospholipase C
      and their refractiveness in the intact cell.

PMID- 11946445
TI  - The arsenate induced calcium release from sarcoplasmic vesicles.

PMID- 11946446
TI  - On the sigmoidal relationship between inhibition of respiration and antimycin
      titer.

PMID- 11946447
TI  - Chemical typing of the immunoglobulins IgM, IgA1 and IgA2.

PMID- 11946449
TI  - Ricin - a potent inhibitor of protein synthesis.

PMID- 11946448
TI  - Dissociation of mammalian D-glyceraldehyde-3-phosphate dehydrogenase into
      monomers.

PMID- 11946450
TI  - Increased activities of hepatic orotidine 5'-phosphate pyrophosphorylase and
      orotidine 5'-phosphate decarboxylase induced by orotate.

PMID- 11946451
TI  - The influence of membrane potential on measurements of C-550 at room temperature.

PMID- 11946452
TI  - A coupling factor from Rhodospirillum rubrum chromatophores.

PMID- 11946453
TI  - The sign of the B(2u) cotton effect and the conformation of pyrimidine and
      azapyrimidine nucleosides.

PMID- 11946454
TI  - The study of hydrocarbon chain mobility in membrane systems using spin-label
      probes.

PMID- 11946455
TI  - Entry site of formylmethionyl-tRNA.

PMID- 11946456
TI  - Photoconversion of chlorophyllide 684 to chlorophyllide 678.

PMID- 11946457
TI  - The localization of polyadenylic sequence at the 5'-end of light nuclear dRNA.

PMID- 11946458
TI  - Properties of ADP- and ATP-1-N-oxide in the adenine nucleotide translocation in
      rat liver mitochondria.

PMID- 11946459
TI  - Inhibition of succinate oxidation in mitochondria by bromothymol blue.

PMID- 11946460
TI  - Role of DNA-RNA hybrids in eukaryots 1. Purification of yeast RNA polymerase B.

PMID- 11946461
TI  - Viral DNA synthesis in isolated nuclei from adenovirus-infected KB cells.

PMID- 11946463
TI  - Effect of glucose and tolbutamide on RNA synthesis in isolated islets of
      langerhans from rat pancreas.

PMID- 11946462
TI  - Pyruvate uptake in rat liver mitochondria: Transport or adsorption?

PMID- 11946464
TI  - Amino acid incorporation into nerve ending structures in vitro.

PMID- 11946465
TI  - Partial characterization of liver proteins following exposure to mercury.

PMID- 11946466
TI  - Effect of carbamyl phosphate on stability of some enzymes of the urea cycle; high
      sensitivity of glutamate dehydrogenase.

PMID- 11946467
TI  - Affinity density perturbation: A new fractionation principle and its illustration
      in a membrane separation.

PMID- 11946468
TI  - Biologically active alkali metal complexones. A 13C-NMR study of ion-dipole
      interaction.

PMID- 11946470
TI  - Dissociation and density characteristics of ribosomes of plant cells.

PMID- 11946469
TI  - Enzymatic preparation of L-tyrosine or 3,4-dihydroxyphenyl-L-alanine from
      pyruvate, ammonia and phenol or pyrocatechol.

PMID- 11946471
TI  - Adenyl cyclase activity in a plasma membrane fraction purified from "ghosts" of
      rat fat cells.

PMID- 11946472
TI  - Gradual release of spermine and RNA from rat liver microsomes treated with EDTA.

PMID- 11946473
TI  - Multiple forms of aspartate aminotransferase. The formation of psi-AAT.

PMID- 11946474
TI  - The effect of saturated pyrimidine bases on RNA conformation.

PMID- 11946475
TI  - The oxidation-reduction potentials of iron-sulfur centers in the site I region of
      the respiratory chain in C. utilis submitochondrial particles.

PMID- 11946476
TI  - Similarities of the heme environment in vertebrate and non-vertebrate oxygen
      binding hemoproteins.

PMID- 11946477
TI  - Solid-phase Edman degradation. The use of p-phenyl diisothiocyanate to attach
      lysine- and arginine-containing peptides to insoluble resins.

PMID- 11946478
TI  - The presence of N-[9-(c-D-ribofuranosyl)purin-6-ylcarbamoyl] threonine in
      isoleucine, threonine and asparagine tRNAs from Escherichia coli.

PMID- 11946479
TI  - The amino acid sequence of the carboxyterminal nonhelical cross link region of
      the alpha 1 chain of calf skin collagen.

PMID- 11946480
TI  - A kinetic study of the activation of yeast inorganic pyrophosphatase by
      magnesium.

PMID- 11946482
TI  - Isolation and characterization of the sweet principle from Dioscoreophyllum
      cumminsii (stapf) Diels.

PMID- 11946481
TI  - On the RNA synthesis in nuclei from immunized rabbit lymph node cells.

PMID- 11946483
TI  - cAMP independent stimulation of lipolysis in isolated fat cells?

PMID- 11946484
TI  - Purification and properties of nucleotide pyrophosphatase from rat liver plasma
      membranes.

PMID- 11946485
TI  - Stimulation by cyclic 3',5'-adenosine monophosphate of RNA synthesis in a
      mammalian cell-free system.

PMID- 11946486
TI  - The non-histone proteins of chromatin.

PMID- 11946487
TI  - Intramolecular cross-linked insulin.

PMID- 11946488
TI  - Properties of the membrane-adenosine triphosphatase complex of Micrococcus
      lysodeikticus: Reversibility of the Mg(2+)-dependent states of the ATPase.

PMID- 11946489
TI  - Identification of a soluble intermediate during synthesis of elastin by embryonic
      chick aortae.

PMID- 11946490
TI  - Carboxymethylation of methionine residues in bovine growth hormone.

PMID- 11946492
TI  - Bacteriophage MS2 RNA and Escherichia coli 23 S ribosomal RNA have a similar
      conformation after reaction with formaldehyde at low pH.

PMID- 11946491
TI  - Ornithine decarboxylase in phytohaemagglutinin stimulated lymphocytes: Control of
      degradation rate by amino acids.

PMID- 11946493
TI  - Energy transduction in photosynthetic bacteria III. Coincidence of coupling
      factor of photosynthesis and respiration in Rhodopseudomonas capsulata.

PMID- 11946494
TI  - Oxygenases involved in thymine and thymidine metabolism in Neurospora crassa.

PMID- 11946495
TI  - The effect of adenine nucleotides upon the 2-oxoglutarate dehydrogenase of
      blowfly flight muscle.

PMID- 11946496
TI  - Evidence for a complex control system for nitrate reductase in wheat leaves.

PMID- 11946497
TI  - The induction of a C(4)-dicarboxylic acid anion translocator in Azotobacter
      vinelandii.

PMID- 11946498
TI  - Specific reassociation of the polypeptide subunit chains of helical myosin
      fragments.

PMID- 11946499
TI  - Template specific inhibition of DNA polymerases from RNA tumor viruses by
      distamycin A and its structural analogues.

PMID- 11946500
TI  - Inactivation of human erythrocyte carbonic anhydrases by bromopyruvate.

PMID- 11946501
TI  - Polypeptide synthesis in Escherichia coli extracts: Effect of spermidine on the
      exchange of ribosomal subunits.

PMID- 11946503
TI  - The energy requirement for activation of succinate metabolism in intact heart
      mitochondria.

PMID- 11946502
TI  - In vitro RNA synthesis on the chromatin template from cortisone-treated rats.

PMID- 11946504
TI  - Conformational analysis of nucleic acids Extended Huckel study on the D-ribose
      (C(3), -exo)-phosphate unit.

PMID- 11946505
TI  - Erythrocuprein and singlet oxygen.

PMID- 11946506
TI  - Inhibition of human lactate dehydrogenase isoenzymes by oestradiol-17-beta in
      vitro.

PMID- 11946507
TI  - Inhibition by colchicine of carbamylcholine induced glycoprotein secretion by the
      submaxillary gland. A possible mechanism of cholinergic induced protein
      secretion.

PMID- 11946508
TI  - Effect of chelerythrine on mitochondrial energy coupling.

PMID- 11946509
TI  - New species of the "oxygenated compound" of cytochrome oxidase.

PMID- 11946510
TI  - Effects of volatile fatty acids, ketone bodies, glucose, and insulin on lipolysis
      in bovine adipose tissue.

PMID- 11946511
TI  - On the differential inhibition of the multiple forms of catalase in mouse tissue.

PMID- 11946512
TI  - Preferential in vivo inhibition of ribosomal ribonucleic acid synthesis in mouse
      liver by the exotoxin of Bacillus thuringiensis.

PMID- 11946513
TI  - Structural analysis of molecular species of nocardomycolic acids from Nocardia
      erythropolis by the combined system of gas chromatography and mass spectrometry.

PMID- 11946514
TI  - ?
AB  - We report here the presence in human milk fat globules membranes of 5'
      nucleotidase, Na(+)-K(+) and Mg(2+) ATPases, and phosphodiesterase which are
      marker enzymes for the plasma membrane. Thiamine-pyrophosphatase, lactose and
      lactosamine synthetase were also found, which are usually considered as Golgi
      apparatus marker enzymes. Lastly, glucose-6-phosphatase, NADH-cytochrome c
      reductase and RNase, characteristic enzymes of the endoplasmic membrane, were
      also present.

PMID- 11946515
TI  - Characterization of cistron specific factors for the initiation of messenger RNA
      translation in E. coli.

PMID- 11946516
TI  - Crystallization and crystallographic data of rabbit muscle phosphorylase a and b.

PMID- 11946518
TI  - Multiple forms of DNA-dependent RNA polymerase from insect tissue.

PMID- 11946517
TI  - ?
AB  - Electrofocusing procedure resolves phenolase of oak's bark in three distinct
      major isozymes showing cresolase and catecholase activities. Their pI are: 6, 7.8
      and 8.2. Little change in ratio of the two activities occurs during isoelectric
      separation. The ultracentrifuged isozymes exhibit sedimentation constant similar
      to the crude enzyme phenolase.

PMID- 11946519
TI  - Biological properties of transfer RNA, synthesized during arginine deprivation in
      stringent and relaxed auxotroph strains of Escherichia coli.

PMID- 11946520
TI  - Bacterial glycophospholipids.

PMID- 11946521
TI  - Reactivation of C(55)-isoprenoid alcohol phosphokinase apoprotein by synthetic
      lecithins.

PMID- 11946522
TI  - On the biosynthesis of cerebrosides: Nonenzymatic N-acylation of psychosine by
      stearoyl coenzyme A.

PMID- 11946523
TI  - Specific inhibition of DNA-polymerases from RNA tumor viruses by some new
      daunomycin derivatives.

PMID- 11946524
TI  - Glycolytic enzyme pattern and constant proportion group in plant cells as related
      to their developmental and functional state.

PMID- 11946525
TI  - Enzymes from carnivorous plants (nepenthes). Isolation of the protease
      nepenthacin.

PMID- 11946526
TI  - Modification of tryptophan 108 in lysozyme by 2-nitro-4-carboxyphenylsulfenyl
      chloride.

PMID- 11946528
TI  - A mutation affecting degradation of stable RNA in Escherichia coli.

PMID- 11946527
TI  - Affinity chromatography of lactate dehydrogenase Model studies demonstrating the
      potential of the technique in the mechanistic investigation as well as in the
      purification of multi-substrate enzymes.

PMID- 11946529
TI  - Trypsin inhibition of cyclic photophosphorylation.

PMID- 11946530
TI  - Reversal of the alkylation of the methionine residues of cytochrome c.

PMID- 11946531
TI  - Evidence for two different complexes of liver alcohol dehydrogenase with
      imidazole.

PMID- 11946532
TI  - Determination of the amino acid sequence of peptides using dipeptidyl
      aminopeptidases.

PMID- 11946533
TI  - Molecular dynamics of cerebroside-cholesterol and sphingomyelin-cholesterol
      interactions: Implications for myelin membrane structure.

PMID- 11946534
TI  - Stimulation of the ferricyanide Hill reaction and coupled photophosphorylation by
      phenazine methasulphate.

PMID- 11946535
TI  - The sequence of the 3'-OH end of the 16 S RNA of Escherichia coli.

PMID- 11946536
TI  - The amino acid sequence of human glucagon.

PMID- 11946537
TI  - The use of deuterated derivatives in peptide mixture analysis by mass
      spectrometry.

PMID- 11946538
TI  - Isolation and properties of human luteinizing hormone subunits.

PMID- 11946539
TI  - Embryonic skin collagen. Replacement of the type of aldimine crosslinks during
      the early growth period.

PMID- 11946540
TI  - 13C NMR spectra of acholeplasma membranes containing 13C labelled phospholipids.

PMID- 11946541
TI  - Functional properties of hemoglobin Rainier.

PMID- 11946542
TI  - Studies on the primary structure of human beta-lipotropic hormone.

PMID- 11946544
TI  - Particulate nature of enzymes involved in the fermentation of ethanol and acetate
      by Clostridium kluyveri.

PMID- 11946543
TI  - Kirromycin, an inhibitor of the 30 S ribosomal subunits function.

PMID- 11946545
TI  - The reaction of pig pancreatic kallikrein with cinnamoyl and indoleacryloyl
      imidazoles.

PMID- 11946546
TI  - Molecular weight determination of polypeptide chains of molluscan and arthropod
      hemocyanins.

PMID- 11946547
TI  - On the mechanism of the antiketogenic action of propionate and succinate in
      isolated rat liver mitochondria.

PMID- 11946548
TI  - A soluble factor from yeast which promotes a GTP-dependent binding of N
      acetylphenylalanyl-tRNA to the ribosomes.

PMID- 11946549
TI  - Evidence for accelerated H(2) O(2) formation by erythrocuprein.

PMID- 11946550
TI  - Preparation of highly labelled 3H-thyreotropin releasing hormone (PGA-HIS
      PRO(NH(2))) by catalytic hydrogenolysis.

PMID- 11946552
TI  - RNA Associated with plasma membranes of ehrlich ascites carcinoma cells.

PMID- 11946551
TI  - Temperature sensitivity of fluorescence probes in the presence of model membranes
      and mitochondria.

PMID- 11946553
TI  - Comparison between human and bird lysozymes: Note concerning the previously
      observed deletion.

PMID- 11946554
TI  - A val-val sequence found in a human monocytic leukemia lysozyme.

PMID- 11946555
TI  - DNA dependent RNA polymerase from rat liver mitochondria.

PMID- 11946556
TI  - The resolution of polyoma DNA by polyacrylamide gel electrophoresis.

PMID- 11946557
TI  - On the specificity of neuraminidase The carboxymethyl alpha-ketoside of N-acetyl
      D-neuraminic acid, a Vibrio cholerae neuraminidase substrate having two anionic
      sites.

PMID- 11946558
TI  - Hypoglycemic effects of insulin covalently linked to polyacrylate.

PMID- 11946559
TI  - Specific synthesis of thyroglobulin on membrane bound thyroid ribosomes.

PMID- 11946560
TI  - On the regulation of succinate dehydrogenase in brain mitochondria.

PMID- 11946561
TI  - Fluorescence changes associated with G-F transformation of actin.

PMID- 11946562
TI  - The amino acid sequence of a cytochrome c from a protozoan Crithidia oncopelti.

PMID- 11946563
TI  - A comparative study of "soluble" RNA polymerase activity of Zajdela hepatoma
      ascites cells and calf thymus.

PMID- 11946564
TI  - Inactivation of ribosomes by colicin E3 in vitro: Requirement for 50 S ribosomal
      subunits.

PMID- 11946565
TI  - Inhibition of NADP-linked malic enzyme by glyoxylate.

PMID- 11946566
TI  - Reaction of cacodylic acid with organic thiols.

PMID- 11946567
TI  - A homoribopolynucleotide synthetase in rat liver nuclei associated with
      ribonucleoprotein particles containing DNA-like RNA.

PMID- 11946568
TI  - Radioactive labeling of protein in vitro by acetylation with 14C-N-(acetoxy)
      succinimide. A new method for quantitative determination of protein in the
      presence of polynucleotides.

PMID- 11946569
TI  - A modification of the 30 S ribosomal subparticle is responsible for stimulation
      of "non-enzymatic" translocation by p-chloromercuribenzoate.

PMID- 11946570
TI  - Inhibition by alpha-amanitin of the oestradiol-induced increase in alpha-amanitin
      insensitive RNA polymerase in immature rat uterus.

PMID- 11946571
TI  - Sialic acid on the synaptosome surface and effect of concanavalin A and trypsin
      on synaptosome electrophoretic mobility.

PMID- 11946572
TI  - The effect of glucagon on DNA synthesis in rat spleen and bone marrow.

PMID- 11946574
TI  - Circular dichroism studies on the binding of L-tryptophan to human serum albumin.

PMID- 11946573
TI  - Three forms of enolase separated by counter-current distribution.

PMID- 11946575
TI  - ?
AB  - The binding constants of the alpha(1)-foetoprotein of the rat embryo serum for
      oestrone and oestradiol-17beta have similar values, i.e. 1 x 10(8) M(-1) in
      average at 25 degrees. There is probably one binding site per mole of binding
      protein. The high alpha(1)-foetoprotein concentration in the rat embryo serum at
      17-19 days of pregnancy explains the exceptionally high levels of fixation of the
      phenolsteroids by this serum.

PMID- 11946577
TI  - The partial amino acid sequence of the major low molecular weight component of
      two human amyloid fibrils.

PMID- 11946576
TI  - Degradation of 4-chloro-4', 6-bis(isopropylamino)-6'-ethylamino-di(s-triazinyl)
      sulphide by plant tissue.

PMID- 11946578
TI  - Biosynthesis of 5, 6-dimethylbenzimidazole from riboflavin Transformation of C-1'
      of riboflavin into C-2 of 5, 6-dimethylbenzimidazole.

PMID- 11946579
TI  - The lack of carotenoid band shifts in a non-photosynthetic, reaction centerless
      mutant of Rhodopseudomonas spheroides.

PMID- 11946580
TI  - Yeast phosphofructokinase: Physical parameters, molecular weight and subunit
      structure.

PMID- 11946581
TI  - The binding sites for Escherichia coli RNA polymerase on lambda phage DNA:
      Various types of binding sites.

PMID- 11946583
TI  - Mischarging in mutant tyrosine transfer RNAs.

PMID- 11946582
TI  - Mutant tyrosine tRNA of altered amino acid specificity.

PMID- 11946584
TI  - Errata.

PMID- 11946586
TI  - Bis-deae-fluorenone: A specific inhibitor of DNA polymerases from RNA tumor
      viruses.

PMID- 11946585
TI  - Deoxyadenylate-rich sequences in mammalian DNA.

PMID- 11946587
TI  - The role of adrenocortical mitochondrial malic enzyme in NADPH generation.

PMID- 11946588
TI  - The 3'-terminal hexanucleotide, CAACCA, is not essential for fragment
      recombination or cross-linking in E. coli tRNA(fMet).

PMID- 11946589
TI  - Chemical fixation of elastase to agarose.

PMID- 11946590
TI  - Stability constants for the complexation of alkali and alkaline-earth cations by
      N-acetyl-neuraminic acid.

PMID- 11946592
TI  - Glyceraldehyde 3-phosphate dehydrogenase: Amino acid sequence of enzyme from
      baker's yeast.

PMID- 11946591
TI  - Newly phosphorylated proteins associated with cytoplasmic dRNA.

PMID- 11946593
TI  - Enzymic synthesis of ethanolamine plasmalogens from 1-alkyl-2-acyl-sn-glycero-3
      (32P)-phosphorylethanolamines by microsomes from rat brain.

PMID- 11946594
TI  - Proton movement accompanying monocarboxylate permeation in hemoglobin-free
      perfused rat liver.

PMID- 11946595
TI  - Energy linked nicotinamide adenine dinucleotide transhydrogenase in a mutant of
      Escherichia coli K12 lacking membrane Mg(2+)&z.sbnd;Ca(2+)-activated adenosine
      triphosphatase.

PMID- 11946596
TI  - Nitrate and nitrite reductase activities in induced chlorophyll mutants of
      barley.

PMID- 11946597
TI  - Proof for the origin of the branch hydroxymethyl carbon of D-apiose from carbon 3
      of D-glucuronic acid.

PMID- 11946598
TI  - NMR Study of ganglion-blocking and curare-like dimethoniums conformation in
      aqueous solutions.

PMID- 11946599
TI  - Comparison of the effects of various detergents on antigen-antibody interaction.

PMID- 11946600
TI  - Microelectrophoresis of proteins and isozymes in flat capillaries. Analysis of
      isozyme spectrum in isolated cells.

PMID- 11946601
TI  - Inhibition by thiostrepton of the IF-2-dependent ribosomal GTPase.

PMID- 11946603
TI  - Short sequences of polyadenylic acid at the 3'-ends of nuclear DNA-like RNA.

PMID- 11946602
TI  - Effect of distamycin A and congocidine on DNA synthesis by rous sarcoma virus
      reverse transcriptase.

PMID- 11946604
TI  - Two enzymatically active forms of lysyl-tRNA synthetase from E. coli B.

PMID- 11946605
TI  - Substrate specificity of lysyl-tRNA synthet ase from E. coli B.

PMID- 11946606
TI  - Automatic monitoring of solid phase synthesis of a decapeptide.

PMID- 11946608
TI  - The binding of Phe-tRNA(Phe) and gly(2)Phe-tRNA(Phe) to reticulocyte ribosomal
      peptidyl sites by a mechanism not involving translocation.

PMID- 11946607
TI  - Aurintricarboxylic acid inhibition of the binding of phenylalanyl-tRNAa to rat
      liver ribosomal subunits.

PMID- 11946609
TI  - Errata.

PMID- 11946610
TI  - Common glycoproteins of synaptic vesicles and the synaptosomal plasma membrane.

PMID- 11946611
TI  - Studies towards the complete sequence determination of proteins by mass
      spectrometry; a rapid procedure for the successful permethylation of histidine
      containing peptides.

PMID- 11946612
TI  - Increased RNase H (hybridase) activity in the integument of blowfly larvae during
      development and under the influence of beta-ecdysone.

PMID- 11946613
TI  - N-Ethylmaleimide inhibition of the induction of gene activity by the hormone
      ecdysone.

PMID- 11946614
TI  - Energetic aspects of the mitochondrial biogenesis.

PMID- 11946615
TI  - Ionophore mediated equilibration of calcium ion gradients in fragmented
      sarcoplasmic reticulum.

PMID- 11946616
TI  - Particulate malate oxidation in strictly aerobic bacteria: The respiratory chain
      of Moraxella lwoffi.

PMID- 11946617
TI  - Fluorescence of the acidic form of Poly C.

PMID- 11946618
TI  - The effect of phospholipase A on human erythrocyte acetylcholinesterase.

PMID- 11946619
TI  - Conversion of 2-mercaptopyrimidine into S-(pyrimidin-2-yl)-cysteine in growing
      Escherichia coli cells.

PMID- 11946620
TI  - Proton magnetic resonance studies on 5'- AMP site in glycogen phosphorylase b.

PMID- 11946621
TI  - Ribonucleoside 5'-aminomethanephosphonates: Synthesis and affinity towards some
      phosphomonoesterases.

PMID- 11946622
TI  - Polymerization of tobacco mosaic virus protein in Na pyrophosphate.

PMID- 11946623
TI  - Immunochemical comparisons of alpha-amylases in developing and germinating wheat
      seeds.

PMID- 11946625
TI  - DNA polymerase activities in brain of chick embryo.

PMID- 11946624
TI  - Phosphotransacetylase associated with the pyruvate dehydrogenase complex from the
      nitrogen fixing Azotobacter vinelandii.

PMID- 11946626
TI  - In vivo inactivation of some ribosomal functions in a potassium depleted mutant
      of E. coli.

PMID- 11946627
TI  - Conformation of native Pseudomonas testosteroni Delta(5)-->(4) 3-oxosteroid
      isomerase.

PMID- 11946628
TI  - Regulation of alpha-ketoglutarate dehydrogenase activity in Acinetobacter.

PMID- 11946629
TI  - Sensitivity to erythromycin of mitochondrial protein synthesis in isolated flight
      muscle mitochondria of the blowfly lucilia.

PMID- 11946630
TI  - The steady state kinetic constants of the Mg-activated myofibrillar ATPase.

PMID- 11946631
TI  - A Requirement for ADP and phosphate in the inhibition of photosystem 1 electron
      transport by salicylaldoxime.

PMID- 11946632
TI  - Methylation of yeast aspartic acid transfer RNA by rat liver extracts.

PMID- 11946633
TI  - Inhibition of cholesterol synthesis by (-)-hydroxycitrate in perfused rat liver.
      Evidence for an extramitochondrial mevalonate synthesis from acetyl coenzyme A.

PMID- 11946634
TI  - Nalidixic acid prevents the induction of yeast cytoplasmic respiration-deficient
      mutants by intercalating drugs.

PMID- 11946636
TI  - Errata.

PMID- 11946635
TI  - ?
AB  - The high molecular weight arylamidase-alkaline phosphatase-complex from rat
      kidney microsomes [1] was carefully dissociated by means of treatment with
      several hydrolytic enzymes or by acidification. Trypsin, chymotrypsin and pronase
      cause a selective solubilization of the enzymes discernible at their different
      electrophoretic mobility in polyacrylamide gel. The lower migrating zone
      represents phosphatase, the faster migrating zone shows arylamidase activity
      (molecular weights 180,000 and 172,000, respectively). Incubation of the complex
      with papain, lipase, neuraminidase or hyaluronidase and incubation at acid
      conditions (pH optimum 5.0) in the absence of any enzyme also yields in the
      appearance of two protein bands. In contrast to the alkaline hydrolases the acid
      hydrolases, the pH 5-treatment and with a certain degree also the lipase liberate
      a second arylamidase zone lying in the phosphatese containing zone during
      polyacrylamide gel electrophoresis. Treatment with SDS and subsequent SDS
      polyacrylamide gel electrophoresis also results in a dissociation of the complex,
      but only in one protein fragement (approx, molecular weight 205,000).

PMID- 11946637
TI  - Dynamics of lipids in membranes: Heterogeneity and the role of cholesterol.

PMID- 11946638
TI  - The isolation and partial characterisation of a new alpha-macroglobulin from
      human pregnancy serum.

PMID- 11946639
TI  - Inhibition by fatty acyl esters of adenine nucleotide translocation in rat-liver
      mitochondria.

PMID- 11946641
TI  - Palmitic acid oxidation by secreting submandibular gland tissue in vitro.

PMID- 11946640
TI  - The influence of various cations on the binding of colchicine by rat brain
      homogenates. Stabilization of intact neurotubules by zinc and cadmium ions.

PMID- 11946642
TI  - Isolation of a trypsin inhibitor (Kunitz inhibitor) from bovine ovary by affinity
      chromatography through trypsin-sepharose.

PMID- 11946643
TI  - Requirement of an acidic proton in substances which act as accelerators of the
      deactivation reactions in the water-splitting enzyme system of photosynthesis.

PMID- 11946644
TI  - Thymine-dimer excision after the preirradiation inhibition of DNA synthesis.

PMID- 11946645
TI  - The energy-linked reduction of NADP(+) by succinate, and its relationship to
      cholesterol side-chain cleavage.

PMID- 11946646
TI  - Molecular orbital studies on the conformation of the terminal aminoacyladenosine
      moieties of tRNA.

PMID- 11946647
TI  - Characterization and arrangement of tryptic fragments from N-terminal region of
      hog pepsin.

PMID- 11946648
TI  - Glucose-6-phosphate-1-epimerase from baker's yeast. A new enzyme.

PMID- 11946649
TI  - Kinetics and dose-response characteristics of adenosine 3',5'-monophosphate
      production by isolated rat adrenal cells stimulated with adrenocorticotrophic
      hormone.

PMID- 11946651
TI  - Gas chromatographic and mass spectrometric analysis of molecular species of
      corynomycolic acids from Corynebacterium ulcerans.

PMID- 11946650
TI  - Conformational changes of neurospora pyruvate kinase induced by tris buffer.

PMID- 11946652
TI  - The complete amino acid sequence of histone F(3) from chicken erythrocytes.

PMID- 11946653
TI  - Effect of methylation of the histidine residue in the active site of alpha
      chymotrypsin on the conformational stability of the enzyme.

PMID- 11946654
TI  - Chemical instabilities of "all-or-none" type in beta - galactosidase induction
      and active transport.

PMID- 11946656
TI  - Errata.

PMID- 11946655
TI  - Mass spectral identification and quantification of phenylthiohydantoin
      derivatives from Edman degradation of proteins: Cysteine derivatives.

PMID- 11946657
TI  - Energy transduction in photosynthetic bacteria V. Role of coupling factor ATPase
      in energy conversion as revealed by light or ATP-induced quenching of atebrine
      fluorescence.

PMID- 11946658
TI  - Electron microscopy of pig liver carboxylesterase.

PMID- 11946660
TI  - Submicrosomal localization of hepatic 3-hydroxy-3-methylglutaryl coenzyme a (HMG
      CoA) reductase.

PMID- 11946659
TI  - Spin-exchange interaction in polyuridilyc acid modified with a spin-labelled
      carbodiimide.

PMID- 11946661
TI  - Degradation of a specific 5 S RNA - 23 S RNA - protein complex by pancreatic
      ribonuclease.

PMID- 11946662
TI  - Catalase multiplicity in normal and acatalasemic mice.

PMID- 11946663
TI  - Identification of the abnormal cholestatic lipoprotein (LP-X) in familial
      lecithin:Cholesterol acyltransferase deficiency.

PMID- 11946664
TI  - The subunit structure of inorganic pyrophosphatase from yeast.

PMID- 11946665
TI  - Multiple forms of rat brain mitochondrial monoamine oxidase. Subcellular
      localization.

PMID- 11946666
TI  - On the mechanism of peptide bond synthesis in the ribosome. 3'-O-phenylalanyl-2'
      O-methyladenosine as a peptide acceptor.

PMID- 11946667
TI  - Recovery of respiration capacity of yeast after photoinhibition.

PMID- 11946668
TI  - Nuclear DNA codes for the photosystem II chlorophyll-protein of chloroplast
      membranes.

PMID- 11946669
TI  - ?
AB  - 1. The energy-independent exchange of alkali metal cations against protons was
      investigated in intact and disintegrated mitochondria. The exchange is not
      specific for different alkali metal ions.2. In intact mitochondria the apparent
      K(m) for the energy-independent exchange range from 5 to 25 mM (Cs(+), Rb(+),
      K(+) 5-10 mM; Na(+) 15 mM; Li(+) 20 mM). At all ions studied the maximum release
      of protons was 15-20 nval/mg protein.3. In disintegrated mitochondria there are
      no differences between the alkali metal ions (apparent K(m) 30 mM; maximum H(+)
      release 50 nval/mg protein).4. Directly accessible binding sites seem to exist in
      the outer membrane. Binding sites in the inner membrane are accessible only after
      disintegration, but not after addition of valinomycin + rotenone.

PMID- 11946670
TI  - Purification of soybean agglutinin by affinity chromatography On sepharose-N
      epsilon-aminocaproyl-beta-D-galactopyranosylamine.

PMID- 11946671
TI  - Lipovitellin synthesizing polysomes: Specific and quantitative isolation.

PMID- 11946672
TI  - Synthesis of tRNA ureido derivatives as substrates for The invention of the
      ribosome peptidyl transferase center.

PMID- 11946673
TI  - Distribution of gangliosides among subcellular fractions from rat liver and
      bovine mammary gland.

PMID- 11946674
TI  - Chemical structures of the TU-C and TU-C(red) products derived from E. coli tRNA.

PMID- 11946676
TI  - On some artifacts of sucrose gradient sedimentation of ribosomes.

PMID- 11946675
TI  - Effects of diethyl pyrocarbonate on the isolation and recovery of bound polysomes
      from a particulate fraction of rat liver.

PMID- 11946677
TI  - Effects of pyrophosphate and diphosphonates on parathyroid hormone- and fluoride
      stimulated adenylate cyclase activity.

PMID- 11946678
TI  - Affinity chromatography of carbonic anhydrase.

PMID- 11946679
TI  - Enhancement of drug oxidation and conjugation by carcinogens in different rat
      tissues.

PMID- 11946680
TI  - The localisation of small molecules in lipid bilayers.

PMID- 11946681
TI  - The composition of glycopeptides, derived from neural membranes, which affect
      neurite growth in vitro.

PMID- 11946682
TI  - Stimulation of 3',5'-cyclic AMP and testosterone production in rat testis in
      vitro.

PMID- 11946683
TI  - The effect of castration and testosterone on some components of the microsomal
      drug metabolising enzyme system in mice.

PMID- 11946684
TI  - Transport of L-glutamate and L-aspartate by membrane vesicles of Bacillus
      subtilis W 23.

PMID- 11946685
TI  - Inhibition of blood coagulation factors by serine esterase inhibitors.

PMID- 11946686
TI  - Kinetic studies on cytochrome b-c(1) interaction in the isolated succinate
      cytochrome c reductase.

PMID- 11946687
TI  - Translation of RNA by L cell extracts: Effect of interferon.

PMID- 11946688
TI  - Close correlation between antimycin titer and cytochrome b(T) content in
      mitochondria of chloramphenicol treated Neurospora crassa.

PMID- 11946689
TI  - Hysteresis without autocatalysis: Simple enzyme systems as possible binary memory
      elements.

PMID- 11946690
TI  - Reconstitution of a sucrase-mediated sugar transport system in lipid membranes.

PMID- 11946691
TI  - Estimation of the rate constants in the michaelis-menten equations without
      restrictions as to time scale.

PMID- 11946692
TI  - An essential methionyl residue in the lac-permease of E. coli.

PMID- 11946693
TI  - The assembly pathway of lactic dehydrogenase isozymes from their unfolded
      subunits.

PMID- 11946694
TI  - Factors controlling the occurrence of site I phosphorylation in C. utilis
      mitochondria.

PMID- 11946695
TI  - Initiation of globin synthesis.

PMID- 11946696
TI  - Subcellular distribution of dolichol phosphate.

PMID- 11946697
TI  - A fragment corresponding to the C(H)2 region of immunoglobulin G (IgG) with
      complement fixing activity.

PMID- 11946698
TI  - Properties of the nicotinic acetylcholine receptor macromolecule of Electrophorus
      electricus.

PMID- 11946699
TI  - Direct biochemical approach to the structural heterogeneity of 30 S ribosomes
      from Escherichia coli.

PMID- 11946701
TI  - In vitro translation of mitochondrial DNA from Neurospora crassa.

PMID- 11946700
TI  - Kinetic mapping of antibody binding sites by chemical relaxation spectroscopy.

PMID- 11946702
TI  - Studies on the bacteriophage MS2. Some nucleotide sequences from the RNA
      polymerase gene.

PMID- 11946703
TI  - Selective inhibition of Rous sarcoma virus production in transformed chick
      fibroblasts by two rifamycin derivatives.

PMID- 11946704
TI  - Specificity of Rous sarcoma virus synthesis.

PMID- 11946705
TI  - Thioredoxin-C': Reconstitution of an active form of Escherichia coli thioredoxin
      from two noncovalently linked cyanogen bromide peptide fragments.

PMID- 11946706
TI  - Action of dimeric ribonucleases on double-stranded RNA.

PMID- 11946707
TI  - Investigation of lipoxygenase functions in chloroplasts and mitochondria from
      Pisum sativum seedlings.

PMID- 11946708
TI  - Artifacts in protein synthesis by mitochondria in vitro.

PMID- 11946709
TI  - The nucleotide sequence of somatic 5 S RNA from Xenopus laevis.

PMID- 11946710
TI  - Sequence heterogeneity of 5 S RNA in Xenopus laevis.

PMID- 11946711
TI  - Spinach chloroplast ribosomes active in protein synthesis.

PMID- 11946712
TI  - Superoxide dismutase activity of Cu(2+) -amino acid chelates.

PMID- 11946713
TI  - Nucleotide sequence of alanine tRNA I from Torulopsis utilis.

PMID- 11946714
TI  - Presence of viral RNA-instructed DNA polymerase in the oncogenic subviral
      particles (virosomes) isolated from the mitochondria of rous sarcoma cells.

PMID- 11946715
TI  - Contact-dependent enhancement of net synthesis of forssman glycolipid antigen and
      hematoside in nil cells at the early stage of cell-to-cell contact.

PMID- 11946716
TI  - Enzymatic preparation of L-tryptophan and 5-hydroxy-L-tryptophan.

PMID- 11946717
TI  - On the nature of the alkaline ionization of horseradish peroxidase.

PMID- 11946718
TI  - Contribution of mitochondrial protein synthesis to the formation of cytochrome
      oxidase in Locusta migratoria.

PMID- 11946719
TI  - Enzymic conversion of aflatoxin B(1) to a derivative inhibiting in vitro
      transcription.

PMID- 11946720
TI  - Porcine luteinizing hormone. The amino acid sequence of the alpha subunit.

PMID- 11946721
TI  - Inhibited respiration and ATPase activity of rat liver mitochondria under
      conditions of matrix condensation.

PMID- 11946723
TI  - Simultaneous release of amylase and peroxidase from the guinea pig submandibular
      gland.

PMID- 11946722
TI  - On the participation of cytochrome P-450 in the formation of 16, 17
      dihydroxylated C(19) steroids from 16-dehydro-C(19) steroids.

PMID- 11946724
TI  - Novel features of DNA-dependent RNA polymerase from protozoan Tetrahymena
      pyriformis.

PMID- 11946725
TI  - Amino acid sequences around the cystine residues in equine growth hormone.

PMID- 11946726
TI  - Effect of trophic hormones on 3',5'-cyclic AMP levels in rat testis interstitial
      tissue and seminiferous tubules.

PMID- 11946727
TI  - A novel RNA-primed polynucleotidepyrophosphorylase from E. Coli.

PMID- 11946728
TI  - Mapping of the binding site of N-fluoroacetyl-D-glucosamine and analogues in hen
      egg lysozyme by 1H and 19F-NMR techniques with Gd(III) and Mn(II) as paramagnetic
      probes.

PMID- 11946729
TI  - Hematinic acid and propentdyopents from bilirubin photo-oxidation in vitro.

PMID- 11946730
TI  - A comparison of the translation of Mengo virus RNA and globin mRNA in krebs
      ascites cell-free extracts.

PMID- 11946731
TI  - Manifestation in the 13C-NMR spectra of two different molecular conformations of
      a cyclic pentapeptide.

PMID- 11946732
TI  - Brownian rotation of the cytochrome oxidase in the mitochondrial inner membrane.

PMID- 11946733
TI  - Phosphoprotein formation during osmo-chemical energy conversion in the membrane
      of the sarcoplasmic reticulum.

PMID- 11946734
TI  - Role of the nuclear cortisol binding protein in the control of transcription of
      thymocyte nuclei by cortisol.

PMID- 11946735
TI  - A small-angle X-ray scattering study on the interaction of actinomycin C(3) with
      deoxyribonucleic acid from calf thymus.

PMID- 11946737
TI  - High resolution NMR investigations on hen's egg yolk plasma.

PMID- 11946736
TI  - Localization of the cholinergic receptor protein in Electrophorus electroplax by
      high resolution autoradiography.

PMID- 11946738
TI  - Structure dependent control of chlorophyll a excitation density: The role of
      oxygen.

PMID- 11946739
TI  - Antibodies against an intermediate on the water side of photosystem II of
      photosynthesis.

PMID- 11946740
TI  - The cause of irreversible polymerisation of tobacco mosaic virus protein.

PMID- 11946741
TI  - The forward and reverse reactions of transaldolase.

PMID- 11946742
TI  - Enzymatic exchange of 3'-terminal AMP in tRNA.

PMID- 11946743
TI  - Abnormal phenylalanyl-tRNA found in serum inhibited Escherichia coli, strain
      0111.

PMID- 11946744
TI  - Rapid labelling of a nonencapsulated RNA of bromegrass mosaic virus.

PMID- 11946745
TI  - Formes multiples de la lysyl-tARN-ligase de levure et leurs sous-unites.
AB  - When Yeast lysyl-tRNA-ligase is extracted in the presence of protease inhibitor
      (PMSF) a homogeneous species of enzyme is obtained, the subunits of which have a
      mass of 70 000 daltons. Endogenous degradation produces lighter active species of
      the enzyme, dimers with subunits in the range 50 000-60 000 daltons. Partial
      trypsinolysis mimics this degradation, which is therefore thought to occur
      through proteolysis.

PMID- 11946747
TI  - Effect of rifampicin on the growth of RNA bacteriophage M12.

PMID- 11946746
TI  - Inhibition of E. coli RNA polymerase by polyadenylic acid.

PMID- 11946748
TI  - Acetylation an artefact in solid phase peptide synthesis. A mass spectrometrical
      investigation.

PMID- 11946749
TI  - The sequences of nucleotides in tRNA(Arg)(III) from brewer's yeast.

PMID- 11946750
TI  - The conformation of gramicidin-A in solution.

PMID- 11946752
TI  - New method of selective and rapid modification of the cytidine residues.

PMID- 11946751
TI  - Spin probe studies of photo-induced structural changes in phospholipid
      multibilayers containing light-sensitive pigments.

PMID- 11946753
TI  - Membrane proteins and membrane structure.

PMID- 11946754
TI  - Purification and properties of a ribonuclease from rat liver polyribosomes.

PMID- 11946755
TI  - Epinephrine and serotonin activation of adenyl cyclase from Tetrahymena
      pyriformis.

PMID- 11946756
TI  - On the types of DNA synthesis in rabbit macrophages.

PMID- 11946757
TI  - Characterization of native sterol carrier protein.

PMID- 11946758
TI  - Affinity chromatography of enzymes on an AMP-analogue: Specific elution of
      dehydrogenases from a general ligand.

PMID- 11946759
TI  - Galactose-6-phosphate dehydrogenase: A new enzyme from mammalian liver.

PMID- 11946760
TI  - Studies on the arrangement of a glucose sensitive phlorizin binding site in the
      microvilli of isolated rat kidney brushborder.

PMID- 11946762
TI  - Studies on aggregated multienzyme systems: Effects of basic proteins and
      phospholipids on oxidase reaction catalyzed by flavoprotein-iron-sulfur-protein
      complexes.

PMID- 11946761
TI  - Demonstration of glucose inhibitable phlorizin binding to renal brushborder
      proteins separated by gel electrophoresis.

PMID- 11946763
TI  - Mass spectrometry of permethylated peptides containing tyrosine and tryptophan.

PMID- 11946764
TI  - Factor and GTP requirements in a eukaryotic protein initiation system with
      reovirus messenger RNA, Met-tRNA(F), and ribosomal subunits.

PMID- 11946765
TI  - NMR of gel and liquid crystalline phospholipids spinning at the 'magic angle'

PMID- 11946766
TI  - Structural studies on ovine growth hormone Complete amino acid sequence,
      partially based on homology with bovine growth hormone.

PMID- 11946767
TI  - The effects of physiological and genetic manipulation on the anion transport
      systems of yeast mitochondria.

PMID- 11946768
TI  - Association of high-molecular weight proteins in the red cell membrane.

PMID- 11946769
TI  - Substrate specificity of ceramide trihexosidase.

PMID- 11946770
TI  - Hormonal interactions at the molecular level: A high resolution proton magnetic
      resonance study of bovine neurophysins and their interactions with oxytocin.

PMID- 11946771
TI  - Effect of D-glucose on the incorporation of 32P into phospholipids of mouse
      pancreatic islets.

PMID- 11946772
TI  - Neutral proteases with different thermostabilities from a facultative strain of
      Bacillus stearothermophilus grown at 40 degrees and at 50 degrees.

PMID- 11946773
TI  - Differential alteration of enzymes under hypobaria and hypoxia.

PMID- 11946774
TI  - Evidence that the stimulation of precursor incorporation into RNA of rat kidney
      by aldosterone is mainly an effect on uptake.

PMID- 11946775
TI  - A hydrosoluble, adjuvant-active mycobacterial "polysaccharide-peptidoglycan".
      Preparation by a simple extraction technique of the bacterial cells (strain
      Peurois).

PMID- 11946776
TI  - Inhibition by alpha-amanitin of chromosomal ribonucleic acid synthesis in rat
      liver.

PMID- 11946777
TI  - The enzymatic incorporation of a dipyrrylmethane into uroporphyrinogen III.

PMID- 11946778
TI  - Determination of secondary structures in isolated or membrane proteins by
      computer curve-fitting analysis of infrared and circular dichroic spectra.

PMID- 11946779
TI  - Metabolism of n-hexadecane in myelinating rat brain.

PMID- 11946780
TI  - Chloramphenicol-resistant mutants of human HeLa cells.

PMID- 11946781
TI  - Pyrolytic conversion of gummiferin into atractyloside. Chemical and biological
      evidence.

PMID- 11946782
TI  - 2-Hydroxylation of pregnenolone by rat liver microsomes.

PMID- 11946783
TI  - Amino acid sequence of the carboxy-terminal cyanogen bromide fragment from bovine
      and human fibrinogen gamma-chains.

PMID- 11946784
TI  - 31P-NMR signals from inner and outer surfaces of phospholipid membranes.

PMID- 11946785
TI  - Impairment of insulin binding to the fat cell plasma membrane in the obese
      hyperglycemic mouse.

PMID- 11946786
TI  - Regulatory effects of mitochondrial lipids on glutamate dehydrogenase (NAD(P)).

PMID- 11946788
TI  - Binding isotherms of tRNA-acriflavine complexes.

PMID- 11946787
TI  - X-Ray photoelectron spectroscopy (XPS) of bovine erythrocuprein.

PMID- 11946789
TI  - Synthesis of RNA on the AT-rich and GC-rich fragments obtained from bacteriophage
      f1 DNA.

PMID- 11946791
TI  - Erratum.

PMID- 11946790
TI  - Synthese von [32P]phosphoenolpyruvat.

PMID- 11946792
TI  - Deficiency in initiation factors of protein synthesis induced by phage T7 in E.
      coli F(+) strains.

PMID- 11946793
TI  - The occurrence of cyclopropane fatty acids in the phospholipids of sheep rumen
      tissues.

PMID- 11946794
TI  - Transport of nuclear DNA into the cytoplasm in animal cells The complexity of the
      transported DNA.

PMID- 11946795
TI  - Evidence for a sulfate transport system in Escherichia coli K-12.

PMID- 11946796
TI  - Variation of polar lipid composition of Bacillus subtilis (Marburg) with
      different growth conditions.

PMID- 11946797
TI  - Separation of native and denatured DNA, RNA and hybrid on sodium iodide
      gradients.

PMID- 11946798
TI  - Synthesis of ADP by isolated "coupling factor" from chloroplasts.

PMID- 11946800
TI  - Inhibition of RNA polymerases from rat liver by the semi-synthetic rifampicin
      derivatives.

PMID- 11946799
TI  - Labelling of lac-permease.

PMID- 11946801
TI  - On the interpretation of energy linked 1-anilino-8-naphthalene sulfonic acid
      fluorescence changes in mitochondrial fragments.

PMID- 11946802
TI  - A new activator in the vitamin b(12)-dependent methionine biosynthesis of
      Escherichia coli.

PMID- 11946803
TI  - Action of alpha-Amanitin in vivo and in vitro.

PMID- 11946804
TI  - The acylation of glycerophosphate in rat liver mitochondria and microsomes as a
      function of fatty acid chain-length.

PMID- 11946805
TI  - Inactivation of the pyruvate formate lyase of Clostridium butyricum.

PMID- 11946806
TI  - Small angle X-ray scattering of LpA, the major lipoprotein family of human plasma
      high density lipoprotein HDL(3).

PMID- 11946807
TI  - The identification of the 3'terminus of the 70 S RNA of murine sarcoma virus
      (moloney).

PMID- 11946808
TI  - Electron transport to nitrogenase in Azotobacter chroococcum: Azotobacter
      flavodoxin hydroquinone as an electron donor.

PMID- 11946809
TI  - Molecular orbital studies on the conformation of phospholipids EHT calculations
      on the polar end.

PMID- 11946810
TI  - Inhibition of in vitro protein synthesis by ppGpp.

PMID- 11946811
TI  - Structural studies of hemoglobin Saint Etienne beta 92 (F8) his --> GLN: A new
      abnormal hemoglobin with loss of beta proximal histidine and absence of heme on
      the beta chains.

PMID- 11946812
TI  - A mutant of Saccharomyces cerevisiae lacking alpha-ketoglutarate dehydrogenase
      activity.

PMID- 11946813
TI  - Cyanogen bromide peptides of the rabbit collagen a1-chain.

PMID- 11946814
TI  - Phosphorylation of rabbit muscle troponin and actin by a 3', 5'-c-AMP-dependent
      protein kinase.

PMID- 11946815
TI  - A discrepancy between the accumulation of L-phenylalanine in the intestinal wall
      and the appearance rate in the blood.

PMID- 11946817
TI  - Secondary methylation of yeast ribosomal RNA.

PMID- 11946816
TI  - An investigation of glucagon biosynthesis in isolated pancreatic islets of guinea
      pigs.

PMID- 11946818
TI  - Carboxy-terminal sequence of retinol-binding protein from human plasma.

PMID- 11946819
TI  - CO(2)-reduction to formate by NADPH. The initial step in the total synthesis of
      acetate from CO(2) in Clostridium thermoaceticum.

PMID- 11946820
TI  - Enzymic synthesis of plasmalogen and O-alkyl glycerolipid by base-exchange
      reaction in the rat brain.

PMID- 11946822
TI  - The enzymic products of the human A and B blood group genes in the serum of
      "Bombay" O(h) donors.

PMID- 11946821
TI  - Amino acid sequence of 37 residues at the carboxyl-terminal end of human plasma
      albumin.

PMID- 11946823
TI  - Stimulation of acetyl-CoA carboxylase by (-)-Hydroxycitrate.

PMID- 11946824
TI  - Purification of yeast phenylalanyl-tRNA synthetase by affinity chromatography, on
      a tRNA(Phe)-sepharose column.

PMID- 11946825
TI  - Lack of specificity in the aminoacyl-tRNA synthetase-catalysed deacylation of
      aminoacyl-tRNA.

PMID- 11946826
TI  - The effect of side chain structure on the incorporation of steroids into lipid
      bilayers (liposomes).

PMID- 11946827
TI  - Further evidence for an androgen-dependent intermediate with a short half life
      required for maximal ribosomal RNA synthesis in the rat ventral prostate.

PMID- 11946828
TI  - Properties of N-bromosuccinimide modified cytochrome oxidase.

PMID- 11946829
TI  - Crevices containing cysteine in the tertiary structure of calf thymus histone F3.

PMID- 11946830
TI  - Genetic heterogeneity of alpha-galactosidase in fabry's disease.

PMID- 11946831
TI  - The dependence of fluorescence quantum yield of the tRNA-acriflavine complexes on
      the conformational changes in tRNA.

PMID- 11946832
TI  - Oxidation in the NADP system and release of GSSG from hemoglobin-free perfused
      rat liver during peroxidatic oxidation of glutathione by hydroperoxides.

PMID- 11946833
TI  - Some observations on the primary acceptor of Rhodopseudomonas viridis.

PMID- 11946834
TI  - Photoinhibition of respiration in bacteria and the cyanophycea Vitreoscilla
      stercoraria.

PMID- 11946835
TI  - Malate dependent synthesis of progesterone in the mitochondrial fraction of human
      term placenta.

PMID- 11946836
TI  - Restricted flexibility of carp 15 S immunoglobulin molecules as revealed by
      fluorescence polarisation.

PMID- 11946838
TI  - Guanosine-diphosphate causing changes in the phosphorylation pattern of adenine
      nucleotides in mitochondria from brown adipose tissue.

PMID- 11946837
TI  - Errata.

PMID- 11946839
TI  - Degradation of lysopine by an inducible membrane-bound oxidase in Agrobacterium
      tumefaciens.

PMID- 11946840
TI  - Formation of retinol glycosides with nucleotide sugars in the presence of whole
      homogenates of rat thyroid.

PMID- 11946841
TI  - Stability of phage T7 gene I mRNA in E. coli cells infected with wild type phage
      and with gene I amber mutants.

PMID- 11946842
TI  - Substrate specificity of fatty acid synthetase from yeast.

PMID- 11946843
TI  - On the photooxidation of a high potential form of cytochrome b-559.

PMID- 11946844
TI  - Irreversible binding of chloramphenicol analogues to E. coli ribosomes.

PMID- 11946845
TI  - Preliminary assignment of the inherited Hl 1 antigen to the apoA-I polypeptide of
      rabbit high density lipoprotein.

PMID- 11946846
TI  - Proton NMR studies on thyrotropin releasing factor.

PMID- 11946847
TI  - A spin label probe for the conformational change on conversion of phosphorylase b
      to phosphorylase a.

PMID- 11946848
TI  - Identification of free cytoplasmic globin mRNA of duck erythroblasts by
      hybridization to anti-messenger DNA and by cell-free protein synthesis.

PMID- 11946849
TI  - Lowered proportion of polysomes and decreased amino acid incorporation by
      ribosomes from denervated muscle.

PMID- 11946850
TI  - Membrane potential as a driving force for ATP synthesis in chloroplasts.

PMID- 11946851
TI  - Isoelectric focusing of proinsulin and intermediate in polyacrylamide gel.

PMID- 11946852
TI  - The membrane proteins of Semliki Forest virus have a hydrophobic part attached to
      the viral membrane.

PMID- 11946853
TI  - Processing of precursor ribosomal RNA in suspensions of higher plant cells.

PMID- 11946855
TI  - A study of the molecular mechanism of the mutagenic action of N-nitroso-N
      alkylurea. Carbamoylation of nucleosides by N-nitroso-N-alkylureas.

PMID- 11946854
TI  - X-Ray diffuse scattering of globular protein solutions: Consideration of the
      solvent influence.

PMID- 11946856
TI  - The complex formed between the A and B proteins of lactose synthetase.

PMID- 11946857
TI  - Multiple steps in the activation of the inactive precursor of bone collagenase by
      trypsin.

PMID- 11946858
TI  - Conductimetric assay of phospholipids and phospholipase A.

PMID- 11946859
TI  - Leucine tRNA(1) from HisT mutant of Salmonella typhimurium lacks two
      pseudouridines.

PMID- 11946860
TI  - Polyamine effect on NADPH-oxidation catalyzed by spinach and adrenal flavoprotein
      iron-sulfur protein complexes and a possible regulatory mechanism.

PMID- 11946861
TI  - Dissimilar separable forms of L-phenylalanine activating enzyme in rat heart
      cytoplasm.

PMID- 11946862
TI  - Lipophilicity and catalysis of photophosphorylation I Sulfonated phenazonium
      compounds are ineffective in mediating cyclic photophosphorylation in photosystem
      I-subchloroplast vesicles.

PMID- 11946863
TI  - Pigeon muscle aldolase: Kinetic properties and primary structure close to the
      substrate binding lysine residue.

PMID- 11946864
TI  - Syntheses and enzymic hydroxylation of protocollagen model peptides containing
      glutamyl or leucyl residue.

PMID- 11946865
TI  - A novel approach to structural analysis of oligonucleotides.

PMID- 11946866
TI  - Determination of the number of cytidine residues in oligonucleotides.

PMID- 11946867
TI  - Inhibition of Ca(2+) transport in mitochondria by selective blockade of membrane
      mucopolysaccharides by hexamine cobaltichloride.

PMID- 11946868
TI  - The conversion of presqualene pyrophosphate into squalene by a cell-free
      preparation of Pisum sativum.

PMID- 11946870
TI  - Errata.

PMID- 11946869
TI  - Chemical properties of the peptide extension in the palpha 1 chain of
      dermatosparactic skin procollagen.

PMID- 11946871
TI  - Effect of fatty acids on pyruvate carboxylation in rat liver mitochondria.

PMID- 11946872
TI  - Carbon-13 nuclear magnetic resonance spectroscopy of living cells and their
      metabolism of a specifically labeled 13C substrate.

PMID- 11946873
TI  - Regulation of pyruvate metabolism by the mitochondrial energy state: The effect
      of palmityl-coenzyme A.

PMID- 11946874
TI  - Stimulation of synthesis of macromolecules in folate-starved Streptococcus
      faecium by folinic acid.

PMID- 11946876
TI  - Short term incubation with bromodeoxyuridine of antigen- or PHA-stimulated cells.

PMID- 11946875
TI  - Apparent co-operative effect of acetyl-CoA on pigeon kidney pyruvate carboxylase.

PMID- 11946877
TI  - Complementary oligonucleotide binding to yeast tRNA Phe (HCl).

PMID- 11946878
TI  - New method to differentiate between some mechanisms of action of enzymes with
      three substrates.

PMID- 11946879
TI  - Standard and non standard products in combined T(1) plus pancreatic RNAase
      fingerprints of HeLa cell rRNA and its precursors.

PMID- 11946880
TI  - Some methylated sequences and the numbers of methyl groups in HeLa cell rRNA.

PMID- 11946882
TI  - Identification of the functionally important cysteinyl residue in pig heart
      aspartate aminotransferase.

PMID- 11946881
TI  - The reaction of ferrocytochrome c with cytochrome oxidase: A new look.

PMID- 11946883
TI  - Discrimination by tRNA of two types of isolated binding sites for E. Coli RNA
      polymerase on phage lambda DNA.

PMID- 11946884
TI  - Purification of a factor for both aerobic-driven and ATP-driven energy-dependent
      transhydrogenases of Escherichia coli.

PMID- 11946885
TI  - Lima bean protease inhibitor: Comparative study of the trypsin and chymotrypsin
      inhibitory activities of four chromatographically pure variants.

PMID- 11946886
TI  - Analysis of grande and petite mitochondrial DNA by DNA-DNA hybridization.

PMID- 11946887
TI  - Relative reactivities of some guanosine residues in the "halves" of tRNA(Val)(1)
      (yeast) and in their complex.

PMID- 11946888
TI  - Amino acid sequence of a 50 S ribosomal protein involved in both EFG and EFT
      dependent GTP-hydrolysis.

PMID- 11946889
TI  - Formation of decane-soluble proteolipids: Influence of monovalent and divalent
      cations.

PMID- 11946890
TI  - The action of light at the structural proteins level on etiolated plastids from
      Zea mays L.

PMID- 11946891
TI  - Reconstitution of the 50S ribosome subunit. Role of proteins L 7 and L 12 in the
      GTPase activities. Site of action of thiostrepton.

PMID- 11946892
TI  - The response of cationic dyes to energy-linked changes of reconstituted
      mitochondrial membrane.

PMID- 11946893
TI  - Translation of oncogenic viral RNA and eukaryotic messenger RNA in the E. coli
      cell-free system.

PMID- 11946894
TI  - Nucleotide sequence of tRNA(Arg)(II) from brewer's yeast.

PMID- 11946895
TI  - Molecular asymmetry of rat liver cytoplasmic DNA polymerase.

PMID- 11946896
TI  - Competitive peptide-inhibitors of leucine aminopeptidase: Specific interaction of
      threonine (tertiary butyl)-peptides with the enzyme from swine kidney and from
      bovine eye lens.

PMID- 11946897
TI  - Phylogeny of hemoglobins: Amino acid sequence of the N-terminal part of a viper
      (vipera aspis) hemoglobin alpha-chain.

PMID- 11946898
TI  - Colicin E3-induced in vitro inactivation of ribosomes from colicin-insensitive
      bacterial species.

PMID- 11946899
TI  - Thyroid-stimulating hormone binding to cultured thyroid cells.

PMID- 11946900
TI  - Influence of the substitution of tryptophan 215 in bovine chymotrypsinogen A on
      its potential enzymic activity.

PMID- 11946901
TI  - The complete amino acid sequence of cytoplasmic aspartate aminotransferase from
      pig heart.

PMID- 11946902
TI  - Abnormal base pairing under the influence of nitrogen mustard.

PMID- 11946903
TI  - The N-terminal and C-terminal amino acid sequence of badger myoglobin.

PMID- 11946904
TI  - Particulate UDP-glucose: Protein transglucosylase from potato tuber.

PMID- 11946905
TI  - A polarographic study on pyridoxal 5'-phosphate binding in glycogen phosphorylase
      b.

PMID- 11946906
TI  - Reactions of methylglyoxal with nucleic acids.

PMID- 11946907
TI  - Molecular heterogeneity of alkaline phosphatase.

PMID- 11946908
TI  - Interactions of the antibiotic, distamycin A, with native DNA and with synthetic
      duplex polydeoxyribonucleotides.

PMID- 11946909
TI  - Oxidation in vivo of the &z.sbnd;SH groups of Streptomyces violaceoruber
      fructokinase.

PMID- 11946910
TI  - The effect of dolichol phosphate on the synthesis of lipid bound sugars in
      embryonic chick brain.

PMID- 11946911
TI  - Involvement of protocatechuic acid in the metabolism of phenylacetic acid by
      Aspergillus niger.

PMID- 11946912
TI  - Mitochondrial protein synthesis in vitro is not an artifact.

PMID- 11946914
TI  - The biochemical modes of action of vitamin e and selenium: A hypothesis.
AB  - In this paper recent experimental work on rat liver is discussed which is
      considered to indicate that a primary function of vitamin E in vivo may be to
      inhibit the oxidation of selenide-containing proteins present in mitochondria and
      in smooth endoplasmic reticulum. On the basis of molecular model building
      studies, it is also suggested that the well-known nutritional relationships
      between vitamin E and dietary polyunsaturated lipids may be due to the occurrence
      within normal membranes of specific complexes between the vitamin and some of the
      molecules of polyunsaturated phospholipids. Without the vitamin, membranes may
      have an abnormally high permeability and they may be subject to degradation by
      endogenous phospholipases in vivo, as well as being abnormally susceptible to
      damage in vitro by dialuric acid and hydrogen peroxide.

PMID- 11946915
TI  - Polymerization of tobacco rattle virus protein.

PMID- 11946916
TI  - Interactions of fluorescent analogs of adenine nucleotides with pyruvate kinase.

PMID- 11946917
TI  - Tungsten incorporation into Azotobacter vinelandii nitrogenase.

PMID- 11946918
TI  - Effect of ethidium bromide on cytochrome synthesis of SV-40 transformed cells.

PMID- 11946919
TI  - Electronic structure of ethidium bromide.

PMID- 11946920
TI  - Nucleotide sequence of tRNA(Ser)(3) from Escherichia coli.

PMID- 11946921
TI  - Distribution of glycerolipid-synthesizing enzymes in the subfractions of rat
      liver microsomes.

PMID- 11946922
TI  - The origin of 30,000 dalton protein in troponin preparations.

PMID- 11946923
TI  - Isolation and physico-chemical characterization of the inhibitory protein of the
      troponin system.

PMID- 11946924
TI  - The membrane potential as the driving force for the accumulation of lysine by
      Staphylococcus aureus.

PMID- 11946925
TI  - The gear effect. III. A simple model for steric induced modification of syn-anti
      equilibrium in nucleotides.

PMID- 11946926
TI  - C(55)-isoprenoid alcohol phosphokinase: The formation of a ternary lipoprotein
      complex.

PMID- 11946927
TI  - Hybridization studies of blue-green algal and higher plant chloroplast DNA.

PMID- 11946928
TI  - NMR Studies of the unfolding of ribonuclease by guanidine hydrochloride. Evidence
      for intermediate states.

PMID- 11946929
TI  - Cleavage site specificity of an endonuclease prepared from Heamophilus influenzae
      strain H-I.

PMID- 11946931
TI  - Resistance and sensitivity to rotenone in Saccharomyces cerevisiae: Possibility
      of a genetic reexamination.

PMID- 11946930
TI  - Carbon-13 NMR spectra of cyclo-glycyl-L-prolyl-glycyl-glycyl-L-prolyl-glycyl:
      assignment of the carbonyl resonances.

PMID- 11946932
TI  - Multiplicity of histone deacetylase from calf thymus.

PMID- 11946933
TI  - The catalytic activity of the inactive conformation of delta-chymotrypsin.

PMID- 11946935
TI  - Purification by affinity chromatography of an enzyme involved in gentamicin
      inactivation.

PMID- 11946934
TI  - Induction of PS II activity and induction of a variable part of the fluorescence
      emission by weak green light in flashed bean leaves.

PMID- 11946936
TI  - Electrophoretic examination of native myosin.

PMID- 11946937
TI  - Microbial degradation of piperonylic acid by Pseudomonas fluorescens.

PMID- 11946938
TI  - Effect of inhibition of spermidine formation on protein and nucleic acid
      synthesis during lymphocyte activation.

PMID- 11946939
TI  - Malic enzyme isozymes in pome fruits.

PMID- 11946940
TI  - The effect of ppGpp on in vitro protein synthesis by a wheat embryo system.

PMID- 11946941
TI  - Purification of an N-acetylglucosaminidase from the limpet Patella vulgata (L.).

PMID- 11946942
TI  - Mode of action of a new colicin.

PMID- 11946943
TI  - Arginyl-tRNA synthetase from Bacillus stearothermophilus: Heat inactivation and
      substrate induced protection.

PMID- 11946944
TI  - Stabilization of histones from rat liver.

PMID- 11946945
TI  - In vivo effect of aflatoxin B(1), on protein synthesis in rat liver.

PMID- 11946946
TI  - ?
AB  - Incubation of liver nuclei from hepatectomised rats with radioactive amino acids
      shows that the rates of synthesis of the globular and residual protein fractions
      increase linearly for up to 24 hr after hepatectomy, whereas the histones show
      maximal incorporation at 15 hr.

PMID- 11946947
TI  - On the isozymes of cathepsin B(1).

PMID- 11946948
TI  - Equilibration of chloride and pyruvate distributions between liver mitochondria
      and medium mediated by organo-tin salts.

PMID- 11946949
TI  - Activation of yeast phosphoglycerate kinase by salts of monovalent cations.

PMID- 11946950
TI  - PMR study of tRNA complexes with low-molecular-weight compounds using Mn(2+)
      ions.

PMID- 11946952
TI  - Erratum.

PMID- 11946951
TI  - Influence of phenobarbital treatment on the turnover of rat liver microsomal
      lipids.

PMID- 11946954
TI  - Control of phosphofructokinase [PFK] activity in conditions simulating those of
      glycolysing yeast extract.

PMID- 11946953
TI  - Mutant tyrosine transfer ribonucleic acids.

PMID- 11946955
TI  - Local anesthetic induced changes of a membrane-bound fluorochrome A link between
      ion uptake and membrane structure.

PMID- 11946956
TI  - Reactions of neutral amino acids plus Na(+) with a cationic amino acid transport
      system.

PMID- 11946957
TI  - Reactivation of arginine genes under the influence of polar mutations.

PMID- 11946959
TI  - Partial resolution of energy-linked reactions in Rhodospirillum rubrum
      chromatophores.

PMID- 11946958
TI  - Studies with ubiquinone-depleted submitochondrial particles.

PMID- 11946960
TI  - Studies on glucose synthesis in rat kidney cell suspensions.

PMID- 11946961
TI  - Effects of chloramphenicol and fusidic acid on polyribosome metabolism in
      escherichia coli.

PMID- 11946962
TI  - On the structure of succinic dehydrogenase flavocoenzyme.

PMID- 11946963
TI  - A reevaluation of the pathway by which glucose is converted into glycogen in a
      liver homogenate.

PMID- 11946965
TI  - The control of ornithinetranscarbamylase activity by arginase in Saccharomyces
      cerevisiae.

PMID- 11946964
TI  - Dissociation-produced loss of regulatory control of homoserine dehydrogenase of
      rhodospirillum rubrum.

PMID- 11946966
TI  - Association of polypeptide initiation factors with 30 S ribosomal subunits.

PMID- 11946967
TI  - Regulation of sugar accumulation by Escherichia coli.

PMID- 11946968
TI  - Nitrate as a hill reagent in a reconstituted chloroplast system.

PMID- 11946970
TI  - Regulation of the synthesis of glyceraldehyde-3-phosphate dehydrogenase in
      Pseudomonas putida.

PMID- 11946969
TI  - On the kinetics of structural transition I of some pancreatic proteins.

PMID- 11946972
TI  - A chromogenic substrate for the investigation of neuraminidases.

PMID- 11946971
TI  - Distribution of hexokinase and glucokinase between parenchymal and non
      parenchymal cells of rat liver.

PMID- 11946973
TI  - Differential transcription of T(4)-DNA by DNA-dependent RNA-polymerase of E. coli
      and A. nidulans.

PMID- 11946974
TI  - Isolation of 5-hydroxytryptamine containing vesicles and of synaptic membranes
      from rat brain.

PMID- 11946975
TI  - Interconversions between inactive and active forms of ribosomal subunits.

PMID- 11946976
TI  - Characterization of DNA in wheat chloroplasts isolated by a new "laceration
      technique"

PMID- 11946977
TI  - Genetic control of the uptake of C(4)-dicarboxylic acids by Escherichia coli.

PMID- 11946978
TI  - Interaction between diazepam and serotonin.

PMID- 11946979
TI  - Stimulation of RNA polymerase activity of rat liver nuclei by cortisol in vitro
      independent of effects on the acetylation and methylation of histones.

PMID- 11946980
TI  - Uptake of serotonin in blood platelets: Dependence on sodium and chloride, and
      inhibition by choline.

PMID- 11946981
TI  - Location of reactive tyrosine residues in trypsin.

PMID- 11946983
TI  - The influence of mitomycin C on the induction of crown-gall tumors.

PMID- 11946982
TI  - Energy-linked oxidation of glutaraldehyde by rat liver mitochondria.

PMID- 11946984
TI  - The N-terminus of ox growth hormone.

PMID- 11946985
TI  - Incorporation of fatty acids into the outer and inner membranes of isolated rat
      liver mitochondria.
AB  - Acyl-CoA: phospholipid acyl-transferase activity as well as phospholipase A
      activity were detected in inner and outer membrane preparations from rat liver
      mitochondria. Both enzyme systems have an optimum pH around 8 and act
      preferentially on phosphatidylethanolamine. While phospholipase A activity is
      much lower in the inner membrane than in the outer membrane of mitochondria the
      reverse is true for the incorporation of (14C)-oleic acid into endogenous
      phosphatidylethanolamine. These results bring an indirect evidence that the inner
      membrane per se possesses a phospholipase A activity.

PMID- 11946986
TI  - ?
AB  - 3',5'-Cyclic AMP inhibits fatty acid synthesis in mitochondria, microsomes and
      supernatant but does not provoke an enrichment in 3H with regard to 14C as it
      occurs during fasting after glucose 6-(3)H or 6-(14)C administration. Insulin
      does not exert any action on "controls" but restores lipogenesis in fasted
      animals in the examinated fractions and normalises the 3H/(14)C ratio, even that
      of microsomes. Control of neoglucogenesis by this hormone is more likely than by
      3',5'-cyclic AMP.

PMID- 11946987
TI  - Steroids in newborns and infants. Hydroxylated cholesterol derivatives in the
      steroid monosulphate fraction from meconium.

PMID- 11946989
TI  - Interaction of basic pancreatic trypsin inhibitor with trypsinogen.

PMID- 11946988
TI  - Differential inactivation of adenosine by human and canine blood.

PMID- 11946990
TI  - Guanidination of horse heart myoglobin.

PMID- 11946991
TI  - Ferredoxin mediated hydrogen formation from NADPH in a cell-free system of
      Clostridium kluyveri.

PMID- 11946992
TI  - The effect of mitochondria on the terminal stages of pyrimidine nucleotides
      biosynthesis.

PMID- 11946993
TI  - The interaction of 1-anilino-8-naphthalene sulphonate with erythrocyte membranes.

PMID- 11946995
TI  - Properties and physiological role of the pep-synthase of A. xylinum.

PMID- 11946994
TI  - Evidence on certain common properties of alkaline phosphatase-like enzymes
      derived from human foetal mineralizing tissues.

PMID- 11946996
TI  - Recent advances in the study of biological systems with rapid reaction
      techniques.

PMID- 11946997
TI  - Arginine metabolism in chlamydomonas reinhardi Arginine deiminase: The first
      enzyme of the catabolic pathway.

PMID- 11946998
TI  - Starting point and direction of biosynthesis of gramicidin S.

PMID- 11946999
TI  - Agrobacterium tumefaciens cross-reacting antigens in sterile crown-gall tumors.

PMID- 11947000
TI  - Isolation and characterization of ribosomes from yeast mitochondria.

PMID- 11947001
TI  - A conformational model of serine transfer RNA proposed on the basis of electron
      microscopy.

PMID- 11947002
TI  - On the tertiary structure of transfer ribonucleic acid.

PMID- 11947003
TI  - Formation of citrate in rat liver mitochondria in response to calcium ions.

PMID- 11947005
TI  - Infra-red investigation of the structural transitions of trypsinogen, trypsin,
      chymotrypsinogen and chymotrypsin.

PMID- 11947004
TI  - The iso-electric fractionation and properties of rabbit transferrin.

PMID- 11947006
TI  - Enzymatic synthesis of psychosine in "Jimpy" mice brain.

PMID- 11947008
TI  - Template activity in liver DNA from rats fed with malondialdehyde.

PMID- 11947007
TI  - Reactivation by phospholipids of CCl(4) inhibited microsomal glucose-6
      phosphatase.

PMID- 11947009
TI  - The effect of chloramphenicol on the biogenesis of mitochondria of rat liver in
      vivo.

PMID- 11947010
TI  - The effect of complexing between poly-A and poly-U on the rate of the slow 1H -->
      3H exchange in adenylic acid.

PMID- 11947011
TI  - Spectral characteristics of lactate oxygenase in aerobic and anaerobic reactions.

PMID- 11947012
TI  - Solubilization of mycoplasma membranes by the nonionic detergent Triton X-100.

PMID- 11947013
TI  - Chlorophyll catalysis and Einstein's photochemical law in photosynthesis.

PMID- 11947014
TI  - The porphobilinogen deamise - uroporphyrinogen III cosynthetase system
      (porphobilinogenase) from bovine liver. Kinetic studies.

PMID- 11947015
TI  - Errata.

PMID- 11947017
TI  - Subfractionation of rat liver plasma membranes.

PMID- 11947016
TI  - Separation and differential sensitivity toward avidin of carbamyl phosphate
      synthetase and urea amidolyase.

PMID- 11947018
TI  - Complex formation by cytochrome c: A clue to the structure and polarity of the
      inner mitochondrial membrane.

PMID- 11947019
TI  - The action of Dio-9 on photophosphorylation.

PMID- 11947020
TI  - The isolation of bovine thyrotrophins by isoelectric focussing.

PMID- 11947021
TI  - Enzymatic hydrolysis of n-substituted met-tRNA(M) and met-tRNA(F).

PMID- 11947022
TI  - Incorporation du desmosterol-3-(3)h dans les sterols du tabac nicotiana tabacum.
AB  - The propionate of 3-(3)H desmosterol has been applied to the leaves of the
      tobacco Nicotiana tabacum Wisconsin. Radioactivity is incorporated into
      cholesterol and campesterol with a yield of about 0.5%; the C(29) sterols are not
      labelled in this experiment.

PMID- 11947023
TI  - Structural and enzymatic properties of the E. coli RNA polymerase subunits.

PMID- 11947024
TI  - Independent genetic regulation of glutamine synthetase and its inactivating
      (adenylating) enzyme in E. coli.

PMID- 11947025
TI  - Regulation of citrate synthase activity by alpha-ketoglutarate. Metabolic and
      taxonomic significance.

PMID- 11947026
TI  - Enzymatic aminoacylation of dissected molecules of baker's yeast valine tRNA 1.

PMID- 11947028
TI  - The sequence of phenylalanine tRNA from E. coli.

PMID- 11947027
TI  - ATP-dependent inactivation of heart muscle pyruvate dehydrogenase and
      reactivation by Mg(++).

PMID- 11947029
TI  - The action of atractyloside and AMP on long-chain fatty acid oxidation and on the
      ATP-dependent fatty acid thiokinase.

PMID- 11947030
TI  - Localisation of proline oxidase and Delta-pyrroline-5-carboxylic acid
      dehydrogenase in rat liver.

PMID- 11947031
TI  - Photolysis kinetics by frequency doubled laser emission.

PMID- 11947032
TI  - Mixed functional oxygenations during the biosynthesis of cyclopenin and
      cyclopenol, benzodiazepine alkaloids of penicillium cyclopium westling.
      Incorporation of molecular oxygen and NIH-shift.

PMID- 11947033
TI  - Biophysical studies of cell membranes A report of the British biophysical society
      meeting held in Birmingham on 15 and 16 April 1969.

PMID- 11947034
TI  - The sequence of 5S ribosomal RNA from two mouse cell lines.

PMID- 11947035
TI  - A peptide, containing the reactive sulfhydryl group of Ca(++) activated ATPase in
      H-meromyosin.

PMID- 11947036
TI  - Inhibitors of rat liver asparaginase.

PMID- 11947037
TI  - Optical and ESR spectra of flavin neutral and cation radicals in unpolar
      solvents.

PMID- 11947038
TI  - An intermediate involved in the formation of 4-aminobenzoic acid from chorismic
      acid in aerobacter aerogenes.

PMID- 11947039
TI  - A study of the enzyme equipment of the yeast rhodotorula gracilis.

PMID- 11947040
TI  - Analysis of kinetic data of allosteric enzymes by a linear plot.

PMID- 11947041
TI  - ?
AB  - The interaction of Actinomycin C(1) (AM) with purine nucleosides was investigated
      by circular dichroism. While dG and dGMP show identical interactions, rG, rGMP
      and 8-aza-GMP show lower tendency for complex formation. ara-G shows no complex
      formation. 6-Thio-GMP shows the strongest affinity for AM in accordance with
      previous results. Substitution on N-7 (methylation, protonation) or C-8 (8-Br-rG,
      8-SH-rG) eliminate completely the complexing capacity. Another type of weaker
      complexes is formed by dA, dAMP and rIMP, indicated by the appearance of a
      positive band at 440 nm. It is concluded that in these complexes both the
      electron donor capacity of the purine base as well as the steric flexibility of
      the sugar around the glycosidic linkage determine their complexing capacity.

PMID- 11947042
TI  - Inhibition of lactate dehydrogenase by high concentrations of pyruvate: The
      nature and removal of the inhibitor.

PMID- 11947043
TI  - Effects of organic solvents on cytochrome c.

PMID- 11947044
TI  - Correlation of the c-terminal sequence of rabbit light chains with allotypes.

PMID- 11947045
TI  - Effect of temperature on potassium - dependent stimulation of transcellular
      migration in normal and neoplastic cells.

PMID- 11947046
TI  - The reassociation of fractionated rabbit reticulocyte ribosomal subunits into
      particles active in polyphenylalanine synthesis.

PMID- 11947048
TI  - Kinetic studies on the interaction of seryl-tRNA synthetase with tRNA(Ser) and
      ser-tRNA(ser) from yeast.

PMID- 11947047
TI  - On zymogens of human pancreatic juice.

PMID- 11947049
TI  - Thermodynamics and kinetics of the interaction of phenylalanine-specific tRNA
      from yeast with its cognate synthetase as studied by the flourescence of the Y
      base.

PMID- 11947050
TI  - Use of substrates with fluorescent donor and acceptor chromophores for the
      kinetic assay of hydrolases.

PMID- 11947051
TI  - Isolation of two fractions with mevalonate kinase activity from Pinus pinaster
      and Agave americana.

PMID- 11947052
TI  - The effect of structural alterations on the reactivity of the nucleotide
      substrate of rabbit muscle pyruvate kinase.

PMID- 11947053
TI  - Specificity of prostaglandin A(1) antiserum Against prostaglandins A(1) and B(1).

PMID- 11947054
TI  - Glycogen synthesis in isolated parenchymal rat liver cells.

PMID- 11947055
TI  - Membranes as acceptors for palmitoyl CoA in fatty acid biosynthesis.

PMID- 11947056
TI  - Conformation and reactivity of DNA V. pH-dependent conformational changes of DNA
      in complexes with poly-L-histidine: Transitions from B- to A-form and to a
      condensed state.

PMID- 11947057
TI  - Crossing over and antibody diversity: The sequence of a new human kappaI light
      chain.

PMID- 11947058
TI  - Effect of mannoheptulose on the dynamics of glucose oxidation in the pancreatic
      beta-cells.

PMID- 11947059
TI  - The effect of Ca(2+) on interaction of acetylcholinesterase with subcellular
      fractions of electric organ tissue from the electric eel.

PMID- 11947060
TI  - Chromosome I as a possible site for some rRNA cistrons in Saccharomyces
      cerevisiae.

PMID- 11947061
TI  - Calorimetric investigation of lysozyme thermal denaturation.

PMID- 11947062
TI  - Transient activation of potato chromatin by gamma irradiation.

PMID- 11947063
TI  - Hormonal control of chromatin availability and of the activity of purified RNA
      polymerases in higher plants.

PMID- 11947064
TI  - Yeast phosphofructokinase IV. Reversibility of the ATP-desensitization.

PMID- 11947065
TI  - Insulin inhibition of membrane-bound adenylate cyclase in Neurospora crassa.

PMID- 11947066
TI  - PMR study of the interaction of ethambutol with polynucleotides and related
      compounds.

PMID- 11947067
TI  - Kinetics of redox changes of nicotinamide-adenine dinucleotides in Ehrlich
      ascites tumour cells.

PMID- 11947068
TI  - Effects of vinblastine and colchicine on the secretion of glucagon from isolated
      guinea-pig islets of langerhans.

PMID- 11947070
TI  - The amino acid sequence of rabbit muscle triose phosphate isomerase.

PMID- 11947069
TI  - Controlled labeling and release of ribonucleoprotein particles in "Nuclear
      columns"

PMID- 11947071
TI  - Blocks in nucleotide phosphodiesterase and alkaline phosphatase activity in
      transformed mammalian cells.

PMID- 11947072
TI  - Kinetic evidence for two different productive substrate binding sites in
      subtilisins.

PMID- 11947073
TI  - Aldosugar dehydrogenases from Neurospora crassa Partial purification and
      characterization of D-arabinose: NAD dehydrogenase.

PMID- 11947074
TI  - Bacterial contamination as a source of error in D-glucose-binding studies using
      intestinal brush border membrane preparations.

PMID- 11947075
TI  - Spectral evidence for the presence of tryptophan in the binding site of
      acetylcholinesterase.

PMID- 11947076
TI  - Multiple forms of starch synthetase in maize varieties as revealed by disc-gel
      electrophoresis and activity staining.

PMID- 11947077
TI  - Increased ribonuclease II activity in a temperature sensitive mutant of
      Escherichia coli.

PMID- 11947078
TI  - Fucoserraten, the female sex attractant of Fucus serratus L. (phaeophyta).

PMID- 11947079
TI  - Reduction of cinnamic acids to cinnamyl alcohols with an enzyme preparation from
      cell suspension cultures of soybean (Glycine max).

PMID- 11947080
TI  - Lycopene accumulation in pigmented radio-resistant Micrococci grown in presence
      of nicotine.

PMID- 11947081
TI  - The effect of the aminoacyl-4-aminohexosyl-cytosine group of antibiotics on
      ribosomal peptidyl transferase.

PMID- 11947082
TI  - Studies on the primary structure and biological activity of a human neurophysin.

PMID- 11947083
TI  - Role of magnesium ion on the interaction between chromomycin A(3) and
      deoxyribonucleic acid.

PMID- 11947084
TI  - Guanyl cyclase in a mammalian photoreceptor.

PMID- 11947085
TI  - Post-translational phosphorylation of phosvitin.

PMID- 11947086
TI  - Membrane associated DNA ("M-band") in growing and confluent 3T3 cells.

PMID- 11947087
TI  - Comparative study of cow and sheep kappa-caseinoglycopeptides: Determination of
      the N-terminal sequences with a sequencer and location of the sugars.

PMID- 11947089
TI  - Apparent co-operative effect of acetyl-CoA on pigeon liver pyruvate carboxylase.

PMID- 11947088
TI  - Selective inhibitions of tRNA methyltransferases by S-adenosylhomocysteine and
      two of its analogues.

PMID- 11947090
TI  - Affinity chromatography of biosynthetic threonine deaminase of Escherichia coli.

PMID- 11947091
TI  - The phosphorylation of colchicine-binding ('microtubular') protein in respiring
      slices of guinea pig cerebral cortex.

PMID- 11947092
TI  - DNA-Dependent RNA polymerase in maturing avian erythrocytes.

PMID- 11947093
TI  - The far-infrared spectra of alkali metal ion complexes with valinomycin,
      beauvericin, nonactin and perhydroantamanide in solution.

PMID- 11947094
TI  - The nature of the metal-ligand bonding in the complexes of ionophores with alkali
      metal ions. A quantum mechanical study of the N,N-dimethyl acetamide and methyl
      acetate interaction with Na(+) and Li(+).

PMID- 11947095
TI  - Isolation and identification of aggregation promoting substances from the bovine
      eye lens.

PMID- 11947096
TI  - Gut glucagon: A common receptor site with pancreatic glucagon in liver cell
      plasma membranes.

PMID- 11947097
TI  - Hydrogen bonding of amino acid side chains to nucleic acid bases.

PMID- 11947098
TI  - Significance of streptozotocin induced nicotinamide-adenine-dinucleotide (NAD)
      degradation in mouse pancreatic islets.

PMID- 11947099
TI  - Specific binding of oligoribonucleotide fractions to E. coli RNA polymerase.

PMID- 11947100
TI  - Nucleotides: Rigid or flexible?

PMID- 11947101
TI  - Fluorescence of tryptophanyl-tRNA(Trp) from E. coli; An interaction between the
      indole and tRNA and its dependence on tRNA conformation.

PMID- 11947102
TI  - On the nature of the light-induced bacteriochlorophyll absorbance changes in
      chromatophores of Rhodospirillum rubrum.

PMID- 11947103
TI  - Amino acid sequences studies of horseradish peroxidase. Tryptic glycopeptide
      containing two histidine residues and a disulfide bridge.

PMID- 11947104
TI  - Insoluble derivatives of polynucleotide-phosphorylase.

PMID- 11947106
TI  - Approaches to the study of enzyme mechanisms lactate dehydrogenase.

PMID- 11947105
TI  - A spin-label carbodiimide as a probe for mitochondrial ATPase.

PMID- 11947107
TI  - Biosynthesis of chondroitin sulfate proteins isolation of four pools of
      chondroitin sulfate proteins differing in their solubility and labeling rates
      with radiosulfate in calf rib cartilage.

PMID- 11947108
TI  - N-terminal chain elongation as evidence for duplication of myoglobin in three
      South American Monkeys.

PMID- 11947109
TI  - Affinity chromatography of porcine pancreatic ribonuclease reinvestigation of the
      N-terminal amino acid sequence.

PMID- 11947110
TI  - A preliminary X-ray crystallographic study of spinach cytochrome C.

PMID- 11947111
TI  - The influence of urea on crystallization and polymorphism of hen lysozyme.

PMID- 11947112
TI  - Separation of adrenergic and cholinergic synaptosomes from immature rat brain.

PMID- 11947114
TI  - Hydrolysis of intact leaf starch grains by glucamylase and alpha-amylase.

PMID- 11947113
TI  - Biosynthesis of phosphatidyl ethanolamine and phosphatidyl choline in spinach
      leaves.

PMID- 11947115
TI  - The interaction of various N-substituted amphetamines with cytochrome P-450 of
      rabbit liver microsomes.

PMID- 11947116
TI  - Differential thermal sensitivities of eukaryotic DNA-dependent RNA polymerases.

PMID- 11947117
TI  - The microheterogeneity of human chorionic gonadotropin (HCG) reflected in the
      beta-subunits.

PMID- 11947118
TI  - Action of bleomycin on programmed synthesis. Influence on DNA and RNA nucleases.

PMID- 11947119
TI  - Strand switch during in vivo polyoma transcription.

PMID- 11947120
TI  - Evidence for involvement of 2 types of reaction in glycolate formation during
      photosynthesis in isolated spinach chloroplasts.

PMID- 11947121
TI  - Nitrate reduction by higher plant peroxidase.

PMID- 11947122
TI  - Mitochondrial DNA metabolism in young Psammechinus miliaris embryos.

PMID- 11947123
TI  - Activation of gamma-glutamyl transpeptidase by monovalent cations.

PMID- 11947124
TI  - Anilinonaphthalene sulfonate and other synthetic ions as mitochondrial membrane
      penetrants: An H(+) pulse technique study.

PMID- 11947125
TI  - Protein kinase activity in cariogenic and non-cariogenic oral streptococci:
      Activation and inhibition by cyclic AMP.

PMID- 11947126
TI  - Adenine binding to glutamate dehydrogenase: Natural and magnetic circular
      dichroism studies.

PMID- 11947127
TI  - Affinity labelling of the active site of the 17beta-oestradiol dehydrogenase of
      human placental cytosol.

PMID- 11947128
TI  - The influence of bilateral superior cervical ganglionectomy, continuous light and
      continuous darkness on the diurnal rhythm of hydroxymethylglutaryl-coenzyme a
      reductase in rat liver.

PMID- 11947129
TI  - Dependence on insulin of the hydrocortisone effect on muscle glycogen content.

PMID- 11947130
TI  - The interaction between atropine sulphate and a proteolipid from cerebral cortex
      studied by light scattering.

PMID- 11947131
TI  - Encephalitogenic basic protein from sciatic nerve.

PMID- 11947132
TI  - DNA-nucleotidyl transferase activity in supernatant and membrane fractions from
      normal and regenerating rat liver mitochondria.

PMID- 11947133
TI  - Differences in composition and size of protein-polysaccharides extracted from pig
      articular cartilage.

PMID- 11947134
TI  - Gluconeogenesis in Escherichia coli The role of triose phosphate isomerase.

PMID- 11947135
TI  - ?
AB  - The complex formed between trypsin and alpha(2)-macroglobulin retains the whole
      hydrolytic activity for benzoylarginine-p-nitroanilide (DL BAPNA). We have
      observed that the inhibition of this activity is dependent on the inhibitor used.
      While soya bean inhibitor (MW = 20 000) is ineffective, the basic pancreatic
      inhibitor (MW = 6 500) progressively inhibits the complex. In this latter case,
      we have observed the formation of a very weakly active ternary compound by two
      methods: kinetic and fluorescence polarization.Such differences suggest either
      that the contact site of trypsin for binding is not the same for each inhibitor
      or that the steric hindrance by macroglobulin prevents large inhibitors from
      reaching the active site. The pancreatic inhibitor can reach this site but its
      affinity is lower for the complex than for free trypsin.

PMID- 11947136
TI  - Application of mass spectrometry to the analysis of proteins containing a N
      terminal pyroglutamic acid residue.

PMID- 11947137
TI  - Micro-disc electrophoresis of proteins in pilocarpine-induced sweat.

PMID- 11947139
TI  - Gluconeogenesis from L-lactate-2-T-2-C(14) in perfused rat liver.

PMID- 11947138
TI  - Evidence for a ping-pong mechanism in the diamine oxidase reaction.

PMID- 11947140
TI  - Mechanism of hormone action The effect of synthetic corticosteroids on liver RNA,
      and hepatic ribonuclease and ribonuclease inhibitor activities in rats.

PMID- 11947141
TI  - Glycyl peptidase in human serum and tissues.

PMID- 11947142
TI  - Isotope equilibration measurements in perfused rat liver synthesizing glucose
      from L-lactate-2-T-2-C(14).

PMID- 11947144
TI  - Acetate utilisation by Rhodopseudomonas spheroides.

PMID- 11947145
TI  - More evidence for bacteria-like protein synthesizing apparatus in chloroplasts
      and mitochondria.

PMID- 11947143
TI  - The isolation of an inhibitor of T-even phage lysozyme from E. coli B cells.

PMID- 11947146
TI  - Protonated polynucleotide structures Thermodynamics of the melting of the acid
      form of polyadenylic acid.

PMID- 11947147
TI  - The mechanism of oxidative phosphorylation A hypothesis derived from studies of
      trimethyltin and triethyltin compounds.

PMID- 11947148
TI  - The site of action of adenosine-5'-triphosphate on beta-galactoside transport in
      Escherischia coli.

PMID- 11947149
TI  - Failure of ethylenediaminetetraacetate or manganese to affect (R)-citrate
      synthesis in Clostridium kluyveri and Clostridium cylindrosporum.

PMID- 11947150
TI  - X-ray small-angle scattering of yeast glyceraldehyde-3-phosphate dehydrogenase as
      a function of saturation with nicotinamide-adenine-dinucleotide.

PMID- 11947151
TI  - Deoxyadenosine diphosphate as substrate for polynucleotide phosphorylase from
      Escherichia coli.

PMID- 11947152
TI  - The molecular weight and dissociation properties of yeast hexokinase.

PMID- 11947153
TI  - ?
AB  - The repeating disaccharide unit of the mucopeptide of the cell wall of
      Mycobacterium smegmatis contains N-acetyl-glucosamine linked to N-glycolyl
      muramic acid. This first identification of N-glycolyl-muramic acid as a natural
      product has been performed by mass spectrometry of the permethylated
      disaccharide. N-glycolyl muramic acid has been synthesized: the natural and
      synthetic products are identical.

PMID- 11947154
TI  - Effect of UV irradiation on the catalytic and allosteric functions of fructose
      1,6-diphosphatase.

PMID- 11947155
TI  - Occurrence of alpha-hydroxy fatty acids in Actinomycetales.

PMID- 11947157
TI  - The effects of aflatoxin B(1) and steroid hormones on polysome binding to
      microsomal membranes as measured by the activity of an enzyme catalysing
      disulphide interchange.

PMID- 11947156
TI  - The photochemical action spectrum of the carbon monoxide inhibited hydroxylation
      of cyclohexane by rat liver microsomes.

PMID- 11947158
TI  - Hydrogen formation from NADH in cell-free extracts of Clostridium kluyveri.
      Acetyl coenzyme A requirement and ferredoxin dependence.

PMID- 11947159
TI  - Identification of the protein moiety of an abnormal human plasma low-density
      lipoprotein in obstructive jaundice.

PMID- 11947160
TI  - Rhythmic changes of hydroxymethylglutaryl coenzyme a reductase activity in livers
      of fed and fasted rats.

PMID- 11947161
TI  - The structures of two glucans from yeast-cell walls.

PMID- 11947162
TI  - The reversibility of photophosphorylation in different classes of spinach
      chloroplasts.

PMID- 11947163
TI  - Oxytocinase and its possible significance in the degradation of oxytocin during
      pregnancy.

PMID- 11947164
TI  - Specificity of mitochondrial and cytoplasmic ribosomes from Neurospora crassa in
      poly-U dependent cell free systems.

PMID- 11947165
TI  - Ribonucleic acid toluidine blue complexes studied by gel electrophoresis and
      spectrophotometry.

PMID- 11947167
TI  - Additional electrophoretic differentiation of LDH(5) and mitochondrial GOT in
      ionic strength and pH gradients.

PMID- 11947166
TI  - Cell fusion induced by lysolecithin.

PMID- 11947168
TI  - Similarities in primary structures of cow colostrum trypsin inhibitor and bovine
      basic pancreatic trypsin inhibitor.

PMID- 11947169
TI  - 2,4 bis (p-chloroanilino)-pyrimidine, an uncoupler of oxidative phosphorylation.

PMID- 11947170
TI  - Adaptation of atomic absorption equipment for pyridine nucleotide assays and
      enzymatic analyses.

PMID- 11947171
TI  - The timing of phospholipid synthesis in neoplastic mast cells.

PMID- 11947172
TI  - Energy conservation in arum spadix mitochondria.

PMID- 11947173
TI  - Synthesis of pyridine nucleotides in yeast.

PMID- 11947174
TI  - A method for purifying methionine-containing peptides by radioactive labelling.

PMID- 11947175
TI  - Physicochemical properties of nucleosides 3. Gel formation by 8-bromoguanosine.

PMID- 11947176
TI  - Effect of carbon monoxide and phenobarbital on hydroxylation of bile acids by rat
      liver microsomes.

PMID- 11947177
TI  - Comparison of fluorescence probe and light-scattering readout of structural
      states of mitochondrial membrane fragments.

PMID- 11947179
TI  - The contamination of rat-liver polyribosomal preparations by non-ribosomal
      proteins.

PMID- 11947178
TI  - The high energy state in chromatophores from Rhodopseudomonas spheroides.

PMID- 11947180
TI  - An altered cytochrome oxidase in a cytoplasmic mutant of Neurospora.

PMID- 11947181
TI  - Different time-lags in testosterone action on sugar metabolism in rat levator ani
      muscle.

PMID- 11947182
TI  - Products of proline peroxidation.

PMID- 11947183
TI  - The reactivity of carboxyl groups in chymotrypsinogen.

PMID- 11947184
TI  - Enhancement of the solubility of S-alkylated proteins by carboxyl group
      modification.

PMID- 11947185
TI  - ?
AB  - The Peptidolipide J (CH(3)-(CH(2))(n)-CO-D Phe-L Ile-L Ile-L Phe-L Ala-O-CH(3))
      is obtained also in acidic form by a chromatographic artefact. In chloroformic
      solutions the ester and the acid behave in a very different way: the acid has a
      stable conformation, as shown by the infra-red spectra and the optical rotary
      dispersion; this conformation is stabilized by hydrogen bonding between two
      peptide chains associated as a carboxylic dimer.

PMID- 11947186
TI  - ?
AB  - N(6)-2'-O-dibutyryl cyclic AMP stimulates glycogenolysis and inhibits fatty acid
      synthesis in rat liver in vivo but has little effect on gluconeogenesis. In
      adipose tissue: it enhances lipogenesis and glycogenesis. These last effects can
      be explained by an increase of insulin release.

PMID- 11947187
TI  - ?
AB  - The kinetics of methaemoglobin substitution reactions have been investigated by
      the stopped-flow technique. Biphasic reactions have been observed with adult and
      fetal methaemoglobin. This behaviour is attributed to different reactivities of
      the chain types. The investigations give evidence of an increasing chain
      reactivity in the sequence alpha-chain < beta-chain < gamma-chain. The
      differences increase with the size of the substituting ligand, indicating steric
      effects.

PMID- 11947188
TI  - The formation of hydroxypyruvyl-tRNA.

PMID- 11947190
TI  - Biosynthesis of cystathionine from homoserine and cysteine by rat liver
      cystathionase.

PMID- 11947189
TI  - Light-induced free radicals in DNA-acridine complexes studied by ESR.

PMID- 11947191
TI  - Characterization of mitochondrial ribosomes from Saccharomyces cerevisiae.

PMID- 11947192
TI  - Comparative studies on the isoleucyl- and leucyl-tRNA synthetases from Bacillus
      stearothermophilus and Escherichia coli: thermal stability of the
      aminoacyladenylate-enzyme complexes.

PMID- 11947193
TI  - Cycloheximide resistant amino acid incorporation into mitochondrial protein from
      Neurospora crassa in vivo.

PMID- 11947194
TI  - The inhibition of 2-oxoglutarate entry into rat liver mitochondria by L
      aspartate.

PMID- 11947195
TI  - Kinetics of succinate uptake by rat-liver mitochondria.

PMID- 11947196
TI  - N(alpha)acyl-aminoacid amides as O-acylating reagents of serine.

PMID- 11947197
TI  - Isolation of glycinin subunits by isoelectric focusing in urea-mercaptoethanol.

PMID- 11947198
TI  - The tyrosyl residues at the active site of aminopeptidase M modifications by
      tetranitromethane.

PMID- 11947200
TI  - Nitration of horse heart ferricytochrome C with tetranitromethane.

PMID- 11947199
TI  - Histidine residues at the active site of aminopeptidase M modifications by
      diazonium-1-h-tetrazole (dht).

PMID- 11947201
TI  - Subunit size of cytoplasmic yeast pyruvate decarboxylase.

PMID- 11947202
TI  - Amino acid composition of cytoplasmic yeast pyruvate decarboxylase.

PMID- 11947203
TI  - Changes in uridine nucleotides during liver perfusion with D-galactosamine.

PMID- 11947204
TI  - Acceptor activity of incomplete aggregate molecules of valine tRNA 1 consisting
      of four fragments.

PMID- 11947205
TI  - Presence of N-formyl-methionyl-transfer RNA in bean chloroplasts.

PMID- 11947206
TI  - 5-Methyl-4-oxo-octane-i,8-dioic acid as a microbiological degradation product of
      cholic acid.

PMID- 11947207
TI  - Isolation of histones from virus-induced tumors.

PMID- 11947208
TI  - Isolation and specificity of cathepsin B.

PMID- 11947209
TI  - The ficin-catalysed hydrolysis of p-nitrophenyl hippurate. Detailed kinetics
      including the measurement of the apparent dissociation constant for the enzyme
      substrate complex.

PMID- 11947210
TI  - Elution of pyruvate kinase from cm-cellulose columns by its allosteric effector.
      A novel method For enzyme purification.

PMID- 11947211
TI  - Interactions substrat-flavine-hemoproteine et stabilite thermique du cytochrome
      b(2) (L-lactate deshydrogenase de la levure).
AB  - We studied the thermal inactivation of yeast cytochrome b(2), the native
      flavohaemoprotein (FHP(n)) and its derivatives, the haemoprotein (HP) obtained by
      dissociation of FMN from FHP(n) and the reconstituted flavohaemoprotein (FHP(r))
      (haemoprotein + FMN). The initial velocity of inactivation is faster in the
      presence of FMN. The substrate (L-lactate) or the competitive inhibitor (oxolate)
      protects only the flavohaemoproteins (FHP(n) and FHP(r)) from thermal
      inactivation by decreasing this velocity. In each case, the "protection
      constant", K(p), is determined.Several interpretations can be proposed to explain
      the lack of protection of the haemoprotein by its substrate: 1) the structure of
      the substrate-binding site depends on the presence of the FMN; 2) the substrate
      binding site exists, but the affinity is too small to be detected; 3) a
      hypothetical scheme is proposed, suggesting that the protein can exist under
      different thermally sensitive forms following whether FMN or substrate is
      present.

PMID- 11947212
TI  - Methionine synthesis: Demonstration of the reversibility of the reaction.

PMID- 11947213
TI  - Effect of chloramphenicol on active amino acid transport.

PMID- 11947214
TI  - Biosynthesis of thyroglobulin: Partial characterization of a labeled 6 S
      precursor.

PMID- 11947215
TI  - ?

PMID- 11947216
TI  - Effect of GTP on the dissociation of 70 S ribosomes.

PMID- 11947217
TI  - Synthesis of N-formyl- and N-succinyl-D-neuraminic acid on the specificity of
      neuraminidase.

PMID- 11947218
TI  - On the identity of human lysozymes isolated from normal and abnormal tissues or
      secretions.

PMID- 11947219
TI  - A conjugate of phallacidin with bovine serum albumin.

PMID- 11947220
TI  - A chondroitin sulphate-protein in kurloff cells from guinea pig spleens.

PMID- 11947221
TI  - ?
AB  - This paper describes an attempt to find a difference between the patterns of
      methylation of E. coli tRNA by extracts of two mouse tissues. Two samples of
      tRNAs, methylated in two separate experiments with extracts of myeloma and of
      liver in presence of either 14C or 3H S-Adenosyl-L-Methionine, were pooled and
      fractionated together on a RPC column. The results show a difference in the
      specificities of the two extracts. Chromatography on DEAE Sephadex suggests that
      the tRNA Met is methylated by the enzymes on the myeloma, while enzymes from
      liver react very little, if at all, with that particular tRNA species. Studies
      have been undertaken in order to find out whether similar differences can also be
      demonstrated in homologous systems.

PMID- 11947222
TI  - Variation of beta-N-acetylhexosaminidase-pattern in Tay-Sachs disease.

PMID- 11947223
TI  - Effect of Distamycin A on the template activity of DNA in a DNA polymerase
      system.

PMID- 11947224
TI  - Electron paramagnetic resonance in biochemistry.

PMID- 11947225
TI  - Binding of 2,3-diphosphoglycerate (2,3 DPGA) to hemoglobin Isolation of peptides
      containing firmly bound 2,3 DPGA.

PMID- 11947226
TI  - Adenine nucleotide translocation in spinach chloroplasts.

PMID- 11947228
TI  - The N-terminal sequence of a human gamma 1 chain of allotype Gm(a(-)f(+)).

PMID- 11947227
TI  - Cooperative helix-coil transitions in half molecules of phenylalanine specific
      tRNA from yeast.

PMID- 11947229
TI  - Association and dissociation of half molecules of phenylalanine specific tRNAs
      from yeast and wheat germ.

PMID- 11947230
TI  - Ferrochelatase in wild-type and in cytoplasmic mutants of neurospora crassa.

PMID- 11947231
TI  - Analysis of nucleic acid derivatives at the subnanomole level. (V) High
      resolution mapping of tritium labelled RNA derivatives.

PMID- 11947232
TI  - Respiration in isolated rat liver nuclear envelopes.

PMID- 11947233
TI  - Electrophoretic comparison of acidic proteins of chromatin from different animal
      tissues.

PMID- 11947234
TI  - Exchange of actin-bound ADP in frog muscle during activity.

PMID- 11947236
TI  - The proton shift across the mitochondrial membrane associated with potassium
      uptake induced by valinomycin.

PMID- 11947235
TI  - Dissociation and reconstitution of the stable multienzyme complex fatty acid
      synthetase from yeast.

PMID- 11947238
TI  - Activation of propionate in rat kidney.

PMID- 11947237
TI  - Mass spectrometry of N-permethylated peptide derivatives; artifacts produced by C
      methylation.

PMID- 11947239
TI  - A new assay method for cell-free polypeptide synthesis using 1-fluoro-2,4
      dinitrobenzene.

PMID- 11947240
TI  - On the mechanism of the alpha-chymotrypsin-catalysed hydrolysis of 4-cis
      benzylidene-2-phenyloxazolin-5-one: Evidence for covalent non-productive binding.

PMID- 11947241
TI  - The proteins of liver and muscle ribosomal subunits: Partial separation by
      carboxymethyl-cellulose column chromatography.

PMID- 11947242
TI  - Effect of echinomycin and olivomycin on RNA synthesis in ehrlich ascites tumour
      cells.

PMID- 11947244
TI  - A plant mannosyl-lipid acting in reversible transfer of mannose.

PMID- 11947243
TI  - Isolation and enzymatic phosphorylation of rat liver cytosol phosphoproteins.

PMID- 11947245
TI  - Mechanism of action of pullulanase.

PMID- 11947247
TI  - Errata.

PMID- 11947246
TI  - Multiple forms of tyrosine aminotransferase in rat liver and their hormonal
      induction in the neonate.

PMID- 11947248
TI  - Comparative biochemistry of photosynthesis A Report of the Seminar Held in Gwatt,
      Switzerland, 21-26 July 1969.

PMID- 11947249
TI  - The reaction of pigeon liver NAD kinase with bromoacetyl pyridine.

PMID- 11947251
TI  - A rifampicin resistent rna-polymerase from E. coli altered in the beta-subunit.

PMID- 11947250
TI  - Steroids in newborns and infants. Identification of 20,22-dihydroxycholesterol
      from the monosulphate and "disulphate" fractions in human meconium.

PMID- 11947252
TI  - The effect of acetylcholine and atropine on the labeling of smooth and rough
      membranes from ovine submaxillary glands.

PMID- 11947253
TI  - Binding of bilirubin to human serum albumin - determination of the dissociation
      constants.

PMID- 11947255
TI  - The action pattern of water-insoluble alpha-amylases.

PMID- 11947254
TI  - The structure of cytochrome c'(3) from desulfovibrio gigas (NCIB 9332).

PMID- 11947256
TI  - Galactose toxicity in the chick: Tissue accumulation of galactose and galactitol.

PMID- 11947257
TI  - The effects of Ca(2+) and ADP on the activity of NAD-linked isocitrate
      dehydrogenase of muscle.

PMID- 11947258
TI  - Biosynthesis of prostaglandins in the renal medulla of rabbit.

PMID- 11947259
TI  - Binding of aureovocin to ribosomes of Streptomyces aureofaciens B-96.

PMID- 11947260
TI  - Distribution of the steroid 11-beta-hydroxylase and the cytochrome P-450 in
      membranes of beef adrenal cortex mitochondria.

PMID- 11947261
TI  - Allosteric behavior of yeast threonine deaminase under partially inactivating
      conditions.

PMID- 11947262
TI  - Biosynthesis of oligosaccharide components of cryptococcus laurentii cell wall.

PMID- 11947263
TI  - Studies on uroporphyrinogen decarboxylase from chicken erythrocytes.

PMID- 11947265
TI  - Species differences in the intestinal response to sulphate ions.

PMID- 11947264
TI  - Inactivation of glyceraldehyde 3-phosphate dehydrogenase by a bifunctional
      reagent.

PMID- 11947266
TI  - Binding of oestradiol to receptor-substances present in extracts from calf
      uterus.

PMID- 11947267
TI  - High-molecular-weight deoxyribonuclease from Verongia aerophoba.

PMID- 11947268
TI  - Carnitine levels in some higher plants.

PMID- 11947270
TI  - Evidence for enzyme-substrate intermediates in the aryl-aldehyde: NADP
      oxidoreductase catalysed reduction of salicylate.

PMID- 11947269
TI  - Two locations of the lac permease sulphydryl in the membrane of E. coli.

PMID- 11947271
TI  - Zonal centrifugation studies on labelling patterns of mitochondrial and nuclear
      DNA in rat liver and hepatoma.

PMID- 11947272
TI  - Use of polyacrylamide gel columns for the separation of nucleotides.

PMID- 11947273
TI  - Fluorescence of collagen - properties of tyrosine residues and another
      fluorescent element in calf skin collagen.

PMID- 11947274
TI  - Configuration of 2-hydroxy acids from brain cerebrosides determined by gas
      chromatography.

PMID- 11947275
TI  - ?
AB  - A toad (Bufo bufo) hemoglobin has been purified and two types of chain have been
      separated by counter-current distribution. The alpha-chain has a N-terminal
      sequence Ac-Ala-Leu and a C-terminal sequence Tyr-Arg. The beta-chain has a N
      terminal sequence Val-His-Leu and a C-terminal sequence Tyr-His.

PMID- 11947276
TI  - Stimulation of the protein-dependent interconversion of two forms of yeast
      phosphofructokinase by a heat-stable fraction from yeast.

PMID- 11947277
TI  - Subunit Composition of horse liver alcohol dehydrogenase isoenzymes.

PMID- 11947278
TI  - Inter-relationships between mitochondrial energy conservation at site I,
      piericidin a sensitivity, and EPR spectra in torulopsis utilis.

PMID- 11947279
TI  - Uridine-5'-monophosphate pyrophosphorylase activity from Escherichia coli.

PMID- 11947280
TI  - A new deoxyribonuclease activity from bacteria infected with T5 bacteriophage.

PMID- 11947281
TI  - Hybridization of heterologous fragments of tRNA from yeast, rat liver and E.
      Coli.

PMID- 11947282
TI  - ?
AB  - A new method for molecular weight determination using polyacrylamidegel
      electrophoresis in a linear gel-concentration-gradient (3-20 degrees ) is
      described. Plotting the log of molecular weights of several standard proteins
      against distance of migration or against 3 log of rate of n-dgration reveal
      linear relationships in ranges of 50.000 - 200.000 or 100.000 - 400.000 Daltons
      respectively. On this basis, a simple method for molecular weight determination
      of proteins (accuracy +/- 5 degrees ) has been devised. The method can also be
      applied for an individual protein in protein mixtures using specific staining
      procedures.

PMID- 11947284
TI  - The requirements of adenosine diphosphate for light-triggered ATPase and ATP-Pi
      exchange reactions in chloroplasts.

PMID- 11947283
TI  - Alternate requirement for pyridoxine or isoleucine in mutants of Escherichia
      coli.

PMID- 11947285
TI  - Magnesium-induced errors of translation in a cell-free system from krebs-II
      ascites carcinoma cells.

PMID- 11947286
TI  - ?

PMID- 11947287
TI  - Endor studies on the covalently bound flavin at the active center of succinate
      dehydrogenase.

PMID- 11947288
TI  - Conformational basis of energy transduction in mitochondria.

PMID- 11947289
TI  - Activation by Hg(2+) of acetoacetyl-CoA reductase in extracts of Rhodopseudomonas
      spheroides and Rhodomicrobium vannielii.

PMID- 11947290
TI  - Purification and some properties of the membrane-bound respiratory nitrate
      reductase of Aerobacter aerogenes.

PMID- 11947291
TI  - Evolution de la composition lipidique de Nocardia asteroides au cours de la
      croissance.
AB  - By addition of 1-(14)C-sodium acedate to the growth medium of Nocardia
      asteroides, it can be shown that the lipid content increases during the
      exponential phase, but does not vary during the stationary phase of the growth.
      Nocardic acid biosynthesis from the medium molecular weight fatty acids occurs
      chiefly during te stationary phase. As these compounds are localised in the cell
      walls, it becomes evident that the lipid envelope of the walls is still
      increasing when the cell growth and division have stopped.

PMID- 11947293
TI  - Crystal and molecular structure of 3'-O-acetyl-2'-deoxy-4-thiothymidine.

PMID- 11947292
TI  - Action of pancreatic amylase on starch oligosaccharides containing single glucose
      side chains.

PMID- 11947294
TI  - Some properties of the leucine-specific tRNA's from Bacillus stearothermophilus.

PMID- 11947295
TI  - Amino acid composition of soluble tryptic peptides from aminoethylated beta-like
      chain of Rana esculenta homoglobin major component.

PMID- 11947296
TI  - Heavy and light chains of a homogeneous immunoglobulin-G.

PMID- 11947298
TI  - Inhibition of (Na(+) + K(+))-activated ATPase by N,N'-dicyclohexylcarbodiimide.

PMID- 11947297
TI  - A comment on the role of magnesium in the control of muscle glycogen synthetase
      kinase.

PMID- 11947299
TI  - DNA dependent RNA polymerase from vegetative cells and from spores of B.Subtilis:
      III. Isolation of a stimulating factor.

PMID- 11947300
TI  - Reversible inhibition of the division of Crithidia luciliae by hydroxyurea and
      its use for obtaining synchronized cultures.

PMID- 11947301
TI  - HAEM catabolism and coupled oxidation of haemproteins.

PMID- 11947302
TI  - Competitive effect of succinate on glycerol-1-phosphate oxidation in liver
      mitochondria from thyroxine-treated rats.

PMID- 11947303
TI  - The effect of mitochondrial oxidations of inhibitors of the dicarboxylate anion
      transporting system.

PMID- 11947304
TI  - Neurochemical correlates of learning and environmental change.

PMID- 11947305
TI  - Factor requirement of formylmethionyl-tRNA binding to E. coli ribosomes
      programmed with a plant viral RNA or a phage RNA.

PMID- 11947307
TI  - On the state of mitochondria in perfused liver: Action of sodium azide on
      respiratory carriers and respiration.

PMID- 11947306
TI  - Biosynthesis of riboflavin. Mutants accumulating 6-hydroxy-2,4,5
      triaminopyrimidine.

PMID- 11947308
TI  - Immunochemical studies on hen's egg-white lysozyme Effect of formylation of the
      tryptophan residues.

PMID- 11947309
TI  - The kinetic behavior of vitamin-B(6) compounds hydration and proton transfer.

PMID- 11947310
TI  - The effect of triethyltin on mitochondrial ion accumulation.

PMID- 11947311
TI  - ?
AB  - The levels of galactosyl diglycerides and the composition of fatty acids of
      Spirodela oligorrhiza (Lemnaceae) plants cultivated on a nutrient containing 1%
      glucose were studied. Controls were grown on a medium without glucose. Between
      the 10(th) and the 25(th) day of growth the ether-soluble lipids of glucose
      stimulated plants contained less monogalactosyl diglyceride (MG) but more
      digalactosyl diglyceride (DG) than controls. In the same time a marked decrease
      of the relative amount of C(18:3) acid and an increase of that of C(18:2) and
      C(16:0) acids was observed. These changes of the lipid composition might be one
      reason for the structural changes in the chloroplast fine structure of glucose
      stimulated Spirodela plants.

PMID- 11947312
TI  - beta-Methyl-delta-keto-Delta(alphabeta)-hexenoic acid and mesityl oxide as acetyl
      donors in the enzymic synthesis of acetylcholine.

PMID- 11947314
TI  - Relationship between vitamin B(12) content and ratio of monounsaturated fatty
      acids to methyl-branched fatty acids in Corynebacterium simplex cells grown on
      hydrocarbons.

PMID- 11947313
TI  - The glycollate oxidising enzyme of algae.

PMID- 11947315
TI  - Characterization by isoelectric focusing of pig heart aspartate aminotransferase.

PMID- 11947317
TI  - Nucleoside diphosphatase in purified preparations of rat liver lysosomes.

PMID- 11947316
TI  - ?
AB  - The synthesis of fatty acids in mitochondria, microsomes and supernatant of rat
      adipose tissue was studied after administration of U-(14)C(-) glucose. The major
      site of fatty acids synthesis was the supernatant in controls and the microsomes
      in insulin-treated animals. The action of insulin cannot be explained only by an
      increase of the intra-cellular penetration of glucose. An action on enzyme
      synthesis is probable.

PMID- 11947318
TI  - Demonstration of three classes of spinach chloroplasts by counter-current
      distribution.

PMID- 11947319
TI  - Studies on the mechanism of action ofncouplers on the transport of inorganic
      phosphate in rat liver mitochondria.

PMID- 11947320
TI  - Polysome-ribosome distribution in isogenic RC(str) and RC(rel) strains of
      Escherichia coli.
AB  - Study of the relative proportions of ribosomes and polysomes released by a
      standardized lysing procedure from isogenic RC(str) and RC(rel) strains of
      Escherichia coli shows that a 20-min period of amino acid starvation of RC(str)
      bacteria reduces the fraction of ribosomes recovered in polysomes to about 60% of
      its value characteristic of exponentially growing cells: A similar starvation
      treatment of the RC(rel) bacteria causes no appreciable reduction in the fraction
      of polysomal ribosomes.

PMID- 11947322
TI  - Studies on the DNA of a virus from Galleria mellonella.

PMID- 11947321
TI  - Isolation, structure and synthesis of a tricarboxylic porphyrin from the
      harderian glands of the rat.

PMID- 11947323
TI  - Difference in reactivity of disulphide bonds of chymotrypsinogen and chymotrypsin
      with beta-mercaptoethanol.

PMID- 11947324
TI  - Plasma hydroxyproline-containing protein (hypro-protein).

PMID- 11947325
TI  - Kinetic isotope effect on the reaction of D-Amino-acid oxidase.

PMID- 11947326
TI  - Proteolytic cleavage of DNA polymerase from Escherichia Coli B into an
      exonuclease unit and a polymerase unit.

PMID- 11947327
TI  - Ratio of the Fab fragments I and II from goat antibodies normal gamma-globulins.

PMID- 11947328
TI  - The effect of aerobic preincubation on anaerobic glycogenolysis in liver slices.

PMID- 11947329
TI  - New method for isolation of the C-terminal fragment of peptides and proteins.

PMID- 11947330
TI  - ?
AB  - Nocardia kirovani cell walls possess a lipidic fraction, a lipolysaccharidic
      fraction and a peptidoglycan. The lipidic part is composed of glycerides, C(16)
      and C(18) free fatty acids, nocardic acids and of a carotenoid pigment. The
      lipopolysaccharidic part is composed of an arabinogalactan esterified by nocardic
      acids. The glycan strand consists of alternating 1-->4 linked N-acetylglucosamine
      and N-glycolylmuramic acid residues substituted by a peptide subunit in which the
      aminoacids Ala, Glu, meso-Dap are present in the molar proportions 1,7:1,2:1.

PMID- 11947331
TI  - A desmethylmenoquinol derivative isolated from green photosynthetic bacteria.

PMID- 11947333
TI  - Fractionation of rat liver tyrosine aminotransferase during the course of
      purification. Further evidence for multiple forms of the enzyme.

PMID- 11947332
TI  - Activation of liver pyruvate kinase by fructose-1-phosphate.

PMID- 11947334
TI  - The function of calcium - cofactor of transketolase from baker's yeast.

PMID- 11947335
TI  - Unequal 32P-labeling of 5'nucleotides in ribonucleic acids of different mammalian
      tissues.

PMID- 11947336
TI  - Isolation of UDP-N-glycolylmuramyl-(Ala, Glu, DAP) from mycobacterium phlei.

PMID- 11947337
TI  - Rifamycin insensitivity of RNA synthesis in yeast.

PMID- 11947338
TI  - Protein synthesis by rabbit reticulocyte ribosomes after treatment with potassium
      chloride.

PMID- 11947339
TI  - Glycyl-tRNA synthetase from rat liver: The role of tRNA in formation of
      glycylhydroxamates.
AB  - One glycyl-tRNA synthetase from rat liver does not form glycylhydroxamates in the
      absence of tRNA. Glycyl-hydroxamate accumulated during the incubation of enzyme
      preparation with glycine, ATP, tRNA and NH(2)OH is formed by non-enzymatic
      hydroxylaminolysis of glycyl-tRNA.

PMID- 11947340
TI  - The ribosomal protein altered in spectinomycin resistant Escherichia coli.

PMID- 11947341
TI  - L-serine deaminating enzymes in Escherichia coli crude extracts.
AB  - (a) The measured L-serine deaminating activity of a crude bacterial extract may
      originate from L-serine deaminase, from biosynthetic L-threonine deaminase, or
      from degradative L-serine deaminase. Nevertheless, the contribution of the
      individual enzymes can be determined.(b) About a half of the L-serine deaminating
      activity of wild type E. coli bacteria, grown in synthetic minimal medium,
      originates from L-serine deaminase and about half from biosynthetic L-threonine
      deaminase.(c) Ninety percent of L-serine deaminating activity of wild type E.
      coli bacteria, grown in yeast extract-tryptone medium, originates from L-serine
      deaminase, and the remainging ten percent from the degradative L-threonine
      deaminase.(d) Conditions have been established in which threonine deaminases are
      eliminated and the activity of L-serine deaminase alone could be measured, even
      in crude extracts.

PMID- 11947342
TI  - Conversion of 4-thiouridine residues in tRNA into radioactive N-4-methylcytidine
      for sequence analysis.

PMID- 11947343
TI  - ?
AB  - The smooth microsomal fractions from Aspergillus oryzae were shown to carry out
      transfer of mannose from GDP-mannose to endogenous proteins acceptors. Data also
      are presented which support that among the subcellular fractions, only the
      microsomes are active in the mannose transfer reaction. All of the radioactive
      material chromatographs with mannose, following acid hydrolysis of microsomal
      fractions.

PMID- 11947344
TI  - RNA from-hela cell microsomes with properties of histone messenger.

PMID- 11947346
TI  - Hydrolysis of proteins during dialysis and ultrafiltration.

PMID- 11947345
TI  - Effect of lipids on aminoacyl-tRNA synthesis in Escherichia coli.

PMID- 11947347
TI  - Stimulation of mitochondrial pyruvate carboxylation by Mn(2+) and the
      distribution of the products between mitochondrion and medium.

PMID- 11947348
TI  - UAG suppressor coded by bacteriophage T4.

PMID- 11947350
TI  - Determination of the quantitative relationship of outer and inner membrane
      proteins in rat liver mitochondria by means of enzymology and electron
      microscopy.

PMID- 11947349
TI  - The 3'-terminal nucleotide sequence of the 23 S ribosomal RNA from Escherichia
      coli.

PMID- 11947351
TI  - Inhibition of oxidative phosphorylation and dinitrophenol stimulated ATPase by
      bathophenanthroline.

PMID- 11947352
TI  - Importance of centrifugation time and homogenate concentration for isolating rat
      liver free polysomes: Effect of fasting.

PMID- 11947353
TI  - Density gradient equilibrium methods applied to blood-group specific
      glycoproteins.
AB  - The blood-group specific glycoproteins of human ovarian cyst fluids have been
      isolated by equilibrium density gradient centrifugation in CsCl; they have been
      characterised in terms of buoyant density, selective salvation and apparent
      molecular weight, both in CsCl and Cs(2)SO(4).

PMID- 11947355
TI  - The preservation of haemocyanin under carbon monoxide.

PMID- 11947354
TI  - Molecular weight estimation of apoferritin sub-units.

PMID- 11947356
TI  - Ribosomal aggregates in chick embryo tissues after exposure to low temperatures.

PMID- 11947357
TI  - 7alpha-dehydroxylation of cholic acid by Clostridium bifermentans strain ATCC
      9714 and Clostridium sordellii strain NCIB 6929.

PMID- 11947358
TI  - Studies on the structure of horse spleen apoferritin.

PMID- 11947359
TI  - Impairment of albumin synthesis in cell-free systems from rat liver.

PMID- 11947360
TI  - Micro-determination of DNA in biological materials by gas-chromatographic and
      isotope dilution analysis of thymine content.

PMID- 11947361
TI  - Mitochondria metabolite transport.

PMID- 11947362
TI  - ?
AB  - From proinsulin-free insulin we obtained maximal purified insulin by means of
      preparative polyacrylamide electrophoresis (PADE). This substance appears in the
      analytical PADE as a uniform band and possesses glycine and phenylalanine as N
      terminal amino acids. By use of the eviscerated rabbit as testing model, the
      product displays a higher hypoglycemic activity as compared with the Toronto
      standard.

PMID- 11947363
TI  - Binding of fluorescent probe, 1-anilino-8-naphthalene sulfonate, to apo
      horseradish peroxidase.

PMID- 11947364
TI  - Quenching of uncoupler fluorescence in relation on the "energized state" in
      chloroplasts.

PMID- 11947365
TI  - ?
AB  - Bovine liver catalase is separated into several distinct bands by electrophoresis
      in a linear concentration gradient of polyacrylamide. Apparently, disc
      electrophoresis under these conditions leads to a series of enzymatic active
      forms of catalase. Their molecular weights are: 248,000; 295,000; 368,000;
      486,000; 705,000 respectively. Density gradient centrifugation separates catalase
      into two components with molecular weights of 252,000 and 316,000. The observed
      differences in molecular weight distribution between gel-electrophoresis and
      density gradient centrifugation are discussed.

PMID- 11947366
TI  - A switch mechanism in the regulation of glycolysis and gluconeogenesis in rat
      liver.

PMID- 11947367
TI  - The oxidation of ketone bodies by rat brain mitochondria.

PMID- 11947368
TI  - Inhibition of glucuronide synthesis by physiological metabolites in liver slices.

PMID- 11947369
TI  - Action of pancreatic alpha-amylase and sweet potato beta-amylase on 6(2)- and
      6(3)-alpha-glucosylmalto-oligosaccharides.

PMID- 11947370
TI  - Riboflavin as precursor in the biosynthesis of the 5,6-Dimethylbenzimidazole
      moiety of vitamin B(12).

PMID- 11947371
TI  - Inhibition of viral RNA synthesis by levallorphan.

PMID- 11947372
TI  - Isolation and antigenic characterization of pFc' fragments from six genetically
      different human G myeloma proteins.

PMID- 11947373
TI  - Catalysis of peptidyl transfer by human tonsil ribosomes and effects of some
      antibiotics.

PMID- 11947374
TI  - Steric course of the histidase reaction.

PMID- 11947375
TI  - Incorporation of label from 5-fluoroorotate into non-ribosomal cytoplasmic RNA in
      rat liver.

PMID- 11947376
TI  - Uncoupling of submitochondrial particles by gramicidin.

PMID- 11947377
TI  - Activation of pyruvate kinase of Mucor Rouxii by manganese ions.

PMID- 11947378
TI  - Cyclic response of energy linked functions of liver Mitochondria to uncoupling
      thiophene derivatives.

PMID- 11947379
TI  - Presence of a non-sulphated glucosaminoglycan in embryonic cornea.
AB  - An analtical evidence has been obtained for the presence of a non-sulphated
      glucosaminoglycan in the young embryonic White Leghorn chicken cornea, consisting
      of nearly equimolar amounts of glucosamine and glucuronic acid. The
      polysaccharide is supposed to be identical with hyaluronic acid.

PMID- 11947380
TI  - Inhibition of NADP dependent oxidoreductases by the 6-aminonicotinamide analogue
      of NADP.

PMID- 11947381
TI  - Serine-containing active center of the trypsin-like protease of crayfish Astacus
      leptodactylus.

PMID- 11947382
TI  - Affinity chromatography of the chorismate mutase from Claviceps paspali based on
      specific interaction with the activator.

PMID- 11947383
TI  - A possible role in protein synthesis for the ribosomal-bound aminopeptidase in
      Escherichia coli B.

PMID- 11947384
TI  - Oviducal lactate dehydrogenase: Hormonal influences on the extracellular
      isoenzymes.

PMID- 11947385
TI  - Fatty acid synthesis in the cell sap and mitochondria of rat brown adipose
      tissue.

PMID- 11947386
TI  - Interaction of a fluorescent probe with erythrocyte membrane and lipids: Effects
      of local anesthetics and calcium.

PMID- 11947387
TI  - Substrate binding to cytochrome P-450 of liver and adrenal microsomes.

PMID- 11947388
TI  - Transient dissociation of lactate dehydrogenase resulting in increased reactivity
      towards iodoacetamide.

PMID- 11947389
TI  - The subunit structure of the pyruvate decarboxylase of Escherichia coli K12.

PMID- 11947391
TI  - Photo-oxidation of horse heart cytochrome c. Evidence for methionine-80 as a heme
      ligand.

PMID- 11947390
TI  - ?
AB  - The alkaline phosphatase of beef, horse, pig and sheep brain have been purified.
      In each case, the alkaline phosphatase activity can be separated into two or
      three components by DEAE-cellulose chromatography and by electrophoresis.
      Although the properties of these enzyme fractions are very similar, there are
      sufficient differences to identify each species.Furthermore two of the three
      components separated in sheep brain differ in their Michaelis constants using
      beta-glycerophosphate as substrate, whereas the two pig brain components are not
      different in this respect. This supports the view of two alkaline phosphatase
      isoenzymes in sheep brain.

PMID- 11947392
TI  - Cobalt deposition in rat erythrocytes and cardiac tissue as evidence for the
      biosynthesis of cobalt porphyrins.

PMID- 11947393
TI  - Substrate and antibiotic binding sites at the peptidyl transferase centre of E.
      coli ribosomes.

PMID- 11947394
TI  - Thermodynamics of the redox reaction of cytochromes c of five different species.

PMID- 11947395
TI  - Oxygen evolution in the dark following illumination of chloroplasts in the
      presence of added manganese.

PMID- 11947397
TI  - Biophysical aspects of photosynthesis a report of the British Biophysical Society
      meeting held in London on 17 and 18 December 1969.

PMID- 11947396
TI  - Uroporphyrinogen III cosynthetase. Evidence for the existence of a polypyrrolic
      substrate in soybean callus tissue.

PMID- 11947398
TI  - Free ribonucleoside triphosphates in mouse liver after alpha-amanitin injection.

PMID- 11947400
TI  - Extrachromosomal inheritance of oligomycin resistance in yeast.

PMID- 11947399
TI  - An initiation factor causing dissociation of E. coli ribosomes.
AB  - Purification of crude initiation factors, essential for polypeptide synthesis in
      cell-free systems of E. coli, yielded a fraction DF which causes dissociation of
      70 S ribosomes. Its stoichiometric action on 70 S ribosomes is antagonized by
      increasing Mg(2+) concentrations but not by the addition of 30 S and 50 S
      subunits washed with high salt concentration. GTP did not stimulate this
      dissociating action. 2 &mgr;g of our most purified preparation caused 100%
      dissociation of 100 &mgr;g of 70 S ribosomes without added GTP. DF-induced
      dissociation is a very rapid process at 37 degrees C and is temperature-dependent
      in the range of 0 degrees -37 degrees C. DF, which is thermolabile factor, is
      much less or not effective with complexed 70 S ribosomes bearing peptidyl-tRNA
      and mRNA.

PMID- 11947401
TI  - The kinetics of salicylate hydroxylase reaction.

PMID- 11947402
TI  - Influence of aurovertin on affinity of mitochondrial adenosine triphosphatase for
      ATP and ADP.

PMID- 11947403
TI  - Inhibition of cathepsin D by diazoacetylnorleucine methyl ester.

PMID- 11947404
TI  - Translation initiation factor C (f2): Selective inactivation of its f-met-tRNA
      binding activity which does not affect messenger RNA binding to the 30 S
      ribosome.

PMID- 11947405
TI  - Ultrafilterable peptides from rat liver and E. coli homogenates.

PMID- 11947406
TI  - Ultrafilterable peptides from homogenates of bovine and porcine submaxillary
      glands.

PMID- 11947407
TI  - ?
AB  - A method is devised for isolation of pure nucleoli, devoid of perinucleolar
      chromatin, from rat hepatoma in a medium of high ionic strength (I = 1, MgCl(2) =
      0.33 M).

PMID- 11947408
TI  - The occurrence of hydroxy-derivatives of phytoene and phytofluene in
      diphenylamine-inhibited cultures of Rhodospirillum rubrum.

PMID- 11947409
TI  - Complex formation between NADase and protein inhibitor from Mycobacterium
      butyricum.

PMID- 11947411
TI  - Rapid loss of cytochrome P-450 and haem caused in the liver microsomes by the
      porphyrogenic agent 2-allyl-2-isopropylacetamide.

PMID- 11947410
TI  - Dissociation of DNA-dependent RNA-polymerase from E. coli in lithium chloride.

PMID- 11947412
TI  - The reactivity of SH groups with a fluorogenic reagent.

PMID- 11947413
TI  - Liporibonucleoprotein complex as an integral part of animal cell plasma
      membranes.

PMID- 11947414
TI  - Errata.

PMID- 11947415
TI  - Errata.

PMID- 11947416
TI  - Functions of polyribosomes attached to membranes of animal cells.

PMID- 11947417
TI  - The rational use of mass spectrometry for amino acid sequence determination in
      peptides and extension of the possibilities of the method.

PMID- 11947418
TI  - Some structural properties of excitable membranes labelled by fluorescent probes.

PMID- 11947419
TI  - On the modes of interaction between competitive inhibitors and the alpha
      chymotrypsin active centre.

PMID- 11947421
TI  - The reduction of the L-cysteine-glutathione mixed disulfide in rat liver.
      involvement of an enzyme catalyzing thiol-disulfide interchange.

PMID- 11947420
TI  - n-Alkylboronic acids as bifunctional reversible inhibitors of alpha-chymotrypsin.

PMID- 11947422
TI  - Reversible inactivation of rat liver serine dehydratase by its substrates.

PMID- 11947423
TI  - Activite succino-deshydrogenasique des microsomes et mode d'incorporation du
      succinate 2,3-(14)C dans les acides gras des microsomes de foie de rat in vitro.
AB  - The incorporations of 2,3-(14)C-succinate 2-(14)C-acetate into fatty acids of
      different cellular fractions of rat liver were studied. Acetate was incorporated
      mainly into supernatant and succinate into microsomal fatty acids. Mitochondria
      only could intensively decarboxylate pyruvate. Avidine inhibited fatty acid
      synthesis from succinate mainly in the supernatant. It is suggested that
      succinate is an important physiological precursor of fatty acids in the liver and
      that an active succino-dehydrogenase is present in microsomes.

PMID- 11947424
TI  - The swelling of rat liver mitochondria induced by a thermostabile factor in crude
      staphylococcal alpha-toxin preparations.

PMID- 11947425
TI  - Conformational changes in the region of the ends of the DNA molecule at
      premelting temperatures.

PMID- 11947426
TI  - Elimination of low-density lipoprotein-polyanion interaction by amino
      modifications.

PMID- 11947427
TI  - Partial purification of phospholipid exchange protein from beef heart.

PMID- 11947429
TI  - Nucleotide sequences of pancreatic ribonuclease digestion products from the 16S
      ribosomal RNA of E. coli.

PMID- 11947428
TI  - Fast numerical simulation of biochemical systems.

PMID- 11947430
TI  - Specific dimer formation of ribosomal RNA and of viral RNA in the presence of
      formaldehyde.

PMID- 11947431
TI  - Effect of sodium dodecyl sulphate on human plasma low density lipoproteins.

PMID- 11947432
TI  - ?
AB  - Several glycolipid fractions have been isolated from the bound lipids of N.
      brasiliensis. The main fraction was characterized as a monoester of
      nocardomycolic acids and D-arabinose. Fractionation of the free lipids yielded a
      glycolipid fraction consisting of nocardomycouc acids, arabinose, galactose and
      several amino acids. This last fraction appears to be similar to wax D of
      Mycobacteria; mild acid treatment of this fraction produced arabinose
      mononorcardomycolate.

PMID- 11947433
TI  - The nature of the enzyme bound intermediates in gramicidin s biosynthesis.

PMID- 11947434
TI  - The solution conformation of bovine carboxypeptidase a: Reaction with 2-hydroxy-5
      nitrobenzyl bromide and N-methylnicotinamide chloride.

PMID- 11947435
TI  - ?

PMID- 11947436
TI  - Chemical composition of slime from three species of myxomycetes.

PMID- 11947437
TI  - ?
AB  - Spontaneous mutants of the bacteriophage fd and mutants resulting from fd
      infected cultures of E. coli grown in the presence of 2.7-diaminofluoren and
      proflavin were isolated by means of free flow electrophoresis.The amino acid
      analyses of the mutant coat proteins (B-proteins) show significant differences in
      comparison with the amino acid analyses of wild type coat protein.

PMID- 11947438
TI  - Rat intestinal alkaline phosphatase. A microheterogeneous series of
      glycoproteins.

PMID- 11947439
TI  - Effect of distamycin a on the structure and template activity of DNA in RNA -
      polymerase system.
AB  - It is shown that native and denatured DNA form complexes with the oligopeptide
      antibiotic distamycin A. The pronounced inhibition of the incorporation of AMP
      into RNA in the DNA directed RNA-polymerase system is due to the interference of
      the antibiotic with DNA.

PMID- 11947440
TI  - Self-assembly of transfer RNA fragments.

PMID- 11947441
TI  - The N-terminus of light chains from rabbit arsonic antibody.

PMID- 11947442
TI  - Energy transfer reactions in aqueous solution. The riboflavin-photooxidation of
      an acridan derivative.

PMID- 11947443
TI  - Interaction of Ac-Phe-tRNA with e. coli ribosomal subunits. 1. Sparsomycin
      induced formation of a complex containing 50 S and 30 S subunits but not mRNA.

PMID- 11947444
TI  - Interaction of Ac-Phe-tRNA with E. coli ribosomal subunits. 2. Resistance of the
      sparsomycin-induced complex to hydroxylamine action.

PMID- 11947445
TI  - 3'(2')-O-Aminoacylnucleotides as polypeptide acceptors at the ribosomal
      peptidyltransferase center.

PMID- 11947446
TI  - Evidence for the presence of half-cystine residues in the capsid of adenovirus
      type 7.

PMID- 11947447
TI  - Inhibition of RNA polymerase and formyltetrahydrofolate synthetase activity by 6
      chloro-8-aza-9-cyclopentylpurine. Structure-activity relationships.
AB  - The structural requirements for inhibition of bacterial RNA polymerase and rabbit
      liver formyltetrahydrofolate synthetase activity by a series of purine nucleoside
      analogs related to 6-chloro-8-aza-9-cyclopentylpurine (689) were investigated. To
      achieve an inhibitory effect, preincubation of the enzyme preparations with the
      purine analogs, prior to assay of enzyme activity, was required. The greatest
      inhibition was produced by analogs containing all three alterations of the purine
      nucleoside structure: the 6-halo, 8-aza, and 9-cyclopentyl groups. It is
      suggested that 689 inhibits the activity of enzymes involved in nucleic acid
      synthesis by a site-directed alkylation.

PMID- 11947448
TI  - The inhibition of DNA-dependent RNA polymerase of E. coli by Showdomycin.

PMID- 11947449
TI  - The effect of pH on the allosteric properties of sheep brain 5'-nucleotidase.

PMID- 11947450
TI  - Changes of mitochondrial NADH(2) oxidation pathways in Torulopsis utilis grown on
      acetate.

PMID- 11947451
TI  - Energy dependent interaction of oligomycin and dicyclo hexylcarbodiimide with the
      mitochondrial membrane.
AB  - The characteristics of the oligomycin and DCCD inhibitions of energy linked
      reactions supported by ATP, indicate that the inhibition is increased by the
      presence of ATP. It is proposed that such an effect can be attributed to an
      energy linked change in the structure of some component of the ATPase,
      facilitating oligomycin interaction with the membrane.

PMID- 11947452
TI  - Unspecific permeation and specific uptake of substances in spinach chloroplasts.

PMID- 11947453
TI  - N-terminal amino acid sequence of intact human fibrinogen.
AB  - N-Terminal amino acid sequence analysis by Edman's phenylisothiocyanate method on
      intact human fibrinogen revealed the first seven amino acids of the gamma-chain:
      H-Tyr-Val-Ala-Thr-Arg-Asp-Asn-.

PMID- 11947454
TI  - The specific binding of copper(II) to alkaline phosphatase of E. coli.

PMID- 11947455
TI  - The relation of the light-induced increase in absorbance at 518 nm to
      photophosphorylation in digitonin subchloroplast particles.

PMID- 11947457
TI  - The use of affinity chromatography for the purification of affinity labeled
      peptides from staphylococcal nuclease.

PMID- 11947456
TI  - Reduction of oxaloacetate by pig liver isocitrate dehydrogenase.
AB  - Pure isocitrate dehydrogenase from pig liver cytoplasm catalyses the reduction of
      oxaloacetate by NADPH at a rate comparable with that observed for the usual
      substrates. The products are NADP and D-malate, the 'unatural' isomer. High
      concentrations of magnesium (25 mM) are necessary for maximal activity, and the
      reaction is not appreciably reversible. These results are discussed in connection
      with the inhibition of the enzyme by mixtures of glyoxylate and oxaloacetate. The
      reduction is not thought to be of physiological importance.

PMID- 11947458
TI  - Transfer of apiose from UDP-apiose to 7-O-(beta-D-glucosyl)-apigenin and 7-O
      (beta-D-glucosyl)-chrysoeriol with an enzyme preparation from parsley.
AB  - An enzyme preparation from parsley (Petroselinum hortense Hoffm.) catalyses the
      formation of apiin (7-O-[beta-D-apio-furanosyl(1-->2)beta-D-glycosyl]-5,7,4'
      trihydroxyflavone) from 7-O-(beta-D-glycosyl)-apigenin and UDP-apiose and of the
      corresponding chrysoeriol-7-apiosyl-glucoside from 7-O(beta-D-glucosyl)
      chrysoeriol and UDP-apiose. Neither free apiose nor cyclic apiose-1,2-phosphate
      can function as a substrate for the transfer reaction.

PMID- 11947459
TI  - Reaction of tetranitromethane with tryptophan and related compounds.

PMID- 11947460
TI  - A spectrofluorometric study of tryptophan 108 in hen egg-white lysozyme.

PMID- 11947461
TI  - Evidence for C-terminal intra-subunit disulphide bridges between immunoglobulin-M
      heavy chains.

PMID- 11947462
TI  - ?
AB  - In alkaline aqueous solution, the sedimentation coefficients of DeoxyHb, HbO(2)
      and HbCO of Lampetra fluviatilis L. are 1.9 +/- 0.1 S. This value corresponds to
      a molecular weight of about 17,000, i.e. the value of a single haem polypeptide
      chain. In weak acidic conditions, both the non-liganded DeoxyHb and the liganded
      forms, HbO2 and HbCO, associate to form dimers and oligomers. The monomer
      oligomer transitions of these compounds take place at different pH values:
      DeoxyHb pHO.5 approximately 6.7; HbO(2) and HbCO pH(O.5) approximately 5.9. With
      respect to the association modus, the equilibrium: 4 Hb &rlhar2; 2
      Hb(2)&rlhar2;Hb(4) may be preferred.

PMID- 11947463
TI  - Galactosylgalactosylglucosylceramide: Galactosyl hydrolase in normal human plasma
      and its absence in patients with fabry's disease.

PMID- 11947464
TI  - Regulation of glycogen metabolism in insect flight muscle. Activation of
      phosphorylase b kinase by calcium and inorganic phosphate.

PMID- 11947465
TI  - Oxygen transfer in the enzymatic conversion of 18O-labelled linoleic acid
      hydroperoxide into the 12-keto-13-hydroxyoctadec-cis-9-enoic acid.

PMID- 11947466
TI  - Biosynthesis and modifications of alpha- and beta-amylases in germinating wheat
      seeds.

PMID- 11947467
TI  - The role of fructose-1,6-diphosphatase in the regulation of glycolysis in
      skeletal muscle.

PMID- 11947469
TI  - Inhibition of polypeptide synthesis in E. Coli cell free system by influenza
      viral protein.

PMID- 11947468
TI  - Preparation and properties of 3-cyano pyridine ad(+), a new analogue of nad(+).

PMID- 11947470
TI  - Errata.

PMID- 11947471
TI  - Errata.

PMID- 11947472
TI  - Isolation and characterization of 2-thiocytidine from a serine transfer
      ribonucleic acid of Escherichia coli.

PMID- 11947473
TI  - Removal of structural proteins from ribosomes by treatment with sodium
      deoxycholate in the presence of EDTA.

PMID- 11947474
TI  - A new approach to the fractionation of ribosomal protein.

PMID- 11947475
TI  - Isolation of a DNA-RNA complex from Euglena gracilis.

PMID- 11947476
TI  - Study on yeast RNA polymerase. Effect of alpha-amanitan and rifampicin.

PMID- 11947477
TI  - Facilitated transport of CO(2) across a membrane bearing carbonic anhydrase.

PMID- 11947478
TI  - On the active site of the NADPH-dependent CoA-SS-Glutathione reductase from yeast
      and rat liver.

PMID- 11947479
TI  - The role of isocitrate lyase in Aspergillus Nidulans.

PMID- 11947480
TI  - 1-Anilino-8-naphthalene sulfonate binding as a probe for substrate mediated
      change in conformation of transaldolase.

PMID- 11947481
TI  - The coupling of the adenylate kinase and creatine kinase equilibria. Calculation
      of substrate and feedback signal levels in muscle.

PMID- 11947482
TI  - The activation of 3-phosphoglycerate dehydrogenase by L-methionine.

PMID- 11947483
TI  - Stimulating effect of haemin on the synthesis of cytochrome c by liver slices.

PMID- 11947484
TI  - Branching action of amylo-1,6-glucosidase/oligo-1,4-->1,4-glucantransferase.

PMID- 11947485
TI  - Free nucleotides of the liver during ontogenesis.

PMID- 11947486
TI  - ?
AB  - In light or dark grown Euglena gracilis cells, the DPG content, in contrast to
      the PG content, is dependent on the carbon source. These results are closely
      related to the electron microscopy observations, showing structural changes in
      mitochondria varying with the carbon source of the media.Two media have been
      used: the first one contains L-glutamic and DL-malic acid and the second contains
      DL-lactic acid. The phospholipidic analysis shows that PC and PE are the two main
      phospholipids.

PMID- 11947487
TI  - L-dopa decarboxylase in the haemocytes of diptera.

PMID- 11947488
TI  - Pteroylglutamates and methionine biosynthesis in isolated chloroplasts.

PMID- 11947489
TI  - Formation of glyoxylate from alpha-hydroxyglutarate by Rhodospirillum rubrum.

PMID- 11947490
TI  - Arginine metabolism in chlamydomonas reinhardi. A new type of citrulline
      degradation.

PMID- 11947491
TI  - On the lactate dehydrogenase of preimplantation mouse ova.

PMID- 11947492
TI  - The excimer fluorescence of tryptophan, tyrosine and d-glyceraldehyde-3-phosphate
      dehydrogenase.

PMID- 11947493
TI  - The stimulatory effect of prostaglandin E(2) on adenyl cyclase in the bovine
      corpus luteum.

PMID- 11947495
TI  - Inhibition of ethanol toxicity by lysine orotate (ORL).

PMID- 11947494
TI  - The presence and possible role of phosphopantothenic acid in gramicidin S
      synthetase.

PMID- 11947496
TI  - A solubilizable acrylamide gel for electrophoresis.

PMID- 11947497
TI  - Purification of L-asparaginase from E. coli by specific adsorption and
      desorption.

PMID- 11947498
TI  - Proton translocation induced by ATPase activity in chloroplasts.
AB  - Proton uptake by chloroplasts was induced by light-triggered ATPase activity. A
      quotient of two was obtained when the initial rate of proton uptake was divided
      by the rate of P(i) released from ATP. Gramicidin accelerated the rate of ATPase
      activity and reduced the H(+)/P(i) ratio to 1.4. The results were found to be
      consistent with the chemiosmotic theory.

PMID- 11947499
TI  - Effect of K(+) and Na(+) on the cytochrome oxidase activity of Halobacterium
      cutirubrum.

PMID- 11947500
TI  - Errata.

PMID- 11947501
TI  - Report of a Symposium held in Hango, Finland, August 16-17, 1969.

PMID- 11947502
TI  - ?
AB  - An incubation mixture of TDP-D-glucose and a purified enzyme extract from E. coli
      B containing TDP-D-glucose 4,6-hydro-lyase was treated with NaB(3)H(4).
      Hydrolysis of the separated sugar nucleotide fraction yielded D-galactose-4-(3)H
      but no 3H-labelled D-glucose. This indicates the presence of TDP-4-keto-D-glucose
      as an intermediate in the enzymatic conversion of TDP-D-glucose to TDP-L
      rhamnose. The stereospecifity of the NaB(3)H(4) reduction can only be explained
      if TDP-4-keto-D-glucose exists as an enzyme bound complex.

PMID- 11947503
TI  - Basic encephalitogenic protein: A simplified purification on sulphoethyl
      sephadex.

PMID- 11947505
TI  - Regulation of NADP-linked isocitrate dehydrogenase activity in Acinetobacter.

PMID- 11947504
TI  - Evolutionary constancy of primary structure in an alpha(A)-chain fragment of
      fibrinogen.

PMID- 11947506
TI  - Functional adaptation of tRNAs to fibroin biosynthesis in the silkgland of Bombyx
      mori L.

PMID- 11947507
TI  - Application of laser Raman spectroscopy to the structural analysis of
      polypeptides in dilute aqueous solution.

PMID- 11947508
TI  - n-pi* Transitions in azapyrimidine nucleosides.

PMID- 11947510
TI  - On the role of the adenosine diphosphate-adenosine triphosphate exchange reaction
      in oxidative phosphorylation: Effect of calcium.

PMID- 11947509
TI  - n-pi* Transitions in pyrimidine cyclonucleosides.

PMID- 11947511
TI  - Active complexes derived from Escherichia coli formylmethionine tRNA which lacks
      the dihydrouridine-containing loop.

PMID- 11947512
TI  - Euflavin and ethidium bromide; inhibitors of mitochondriogenesis in regenerating
      rat liver.

PMID- 11947513
TI  - On the rate of reaction of an organic phosphate (ATP) with deoxy hemoglobin.

PMID- 11947514
TI  - Purification of trypsin by affinity chromatography on ovomucoid-sepharose resin.

PMID- 11947515
TI  - Zn(2+)-Induced stimulation of nuclear RNA synthesis in rat liver.

PMID- 11947516
TI  - Errata.

PMID- 11947517
TI  - Amantis. Chemistry and action.

PMID- 11947518
TI  - The ribosomal incorporation of hexosamine into glycoprotein in a mouse myeloma.

PMID- 11947519
TI  - N-Formylmethionyl transfer ribonucleic acid in Pseudomonas aeruginosa.

PMID- 11947520
TI  - Circular structures in preparations of the replicative form of
      encephalomyocarditis virus RNA.

PMID- 11947521
TI  - Synthetic inhibitors of Vibrio cholerae neuraminidase and neuraminidases of some
      influenza virus strains.

PMID- 11947522
TI  - ?
AB  - Yeast phosphofructokinase exists in several enzymically active, interconvertible
      forms with molecular weights of 180,000, 370,000, 570,000 and 750,000. With disc
      electrophoresis catalytically active aggregation products with molecular weights
      of more than one million can be detected.In alkaline media fragmentation of
      phosphofructokinase occurs, leading to a variety of catalytically inactive
      products. These seem to be oligomers of subunits with 60,000 daltons. A model of
      the complex subunit structure of yeast phosphofructokinase is suggested. The
      various catalytically active forms of the enzyme are considered as polymers of
      180,000 monomers, which themselves are enzymatically active and which are
      composed of three 60,000 subunits.

PMID- 11947523
TI  - The kinetic complexity of Euglena gracilis chloroplasts DNA.

PMID- 11947524
TI  - Glycoprotein biosynthesis. Subcellular localization and activity in 3T3 and SV
      3T3 fibroblasts of glycoprotein. N-acetylglucosaminyl transferases.

PMID- 11947525
TI  - Experimental evidence for covalent binding of an organic nitroxide free radical
      to radiation induced DNA radicals.

PMID- 11947526
TI  - Binding of 2,3-diphosphoglycerate to normal and abnormal oxyhemoglobin.

PMID- 11947527
TI  - Effect of sulphydryl-blocking reagents on mitochondrial anion-exchange reactions
      involving phosphate.

PMID- 11947528
TI  - MAK chromatography at 35 degrees causes denaturation of 5 S RNA from Salmonella
      typhimurium.

PMID- 11947529
TI  - Release of the periplasmic ribonuclease I into the medium from Escherichia coli
      treated with the membrane-active polypeptide antibiotic polymyxin B.

PMID- 11947531
TI  - Stereochemistry of the oxidation at the beta-carbon of butyryl-SCoA.

PMID- 11947530
TI  - Role of the 2'-hydroxyl in polynucleotide conformation. Poly 2'-O-methyluridylic
      acid.

PMID- 11947532
TI  - Simultaneous assay of RNA polymerase I and II in nuclei isolated from resting and
      growing rat liver with the use of alpha-amanitin.

PMID- 11947533
TI  - Effects of cortisol on RNA synthesis as detected by hybridization with
      differentially renaturing DNA species.

PMID- 11947535
TI  - Errata.

PMID- 11947534
TI  - On the mechanism of amide-bond-cleavage catalyzed by aminopeptidase M. kinetic
      studies.

PMID- 11947536
TI  - Chemistry and molecular biology of flavins and flavoproteins.

PMID- 11947537
TI  - Role of lysine 18 in active center of cow colostrum trypsin inhibitor.

PMID- 11947539
TI  - Suppression of pyruvate carboxylase by glucose in the perfused rat liver.

PMID- 11947540
TI  - The viscosity change during the polymerization of nucleoside diphosphates.

PMID- 11947538
TI  - Some physical properties of alkaline phosphatases found in various tissues of AKR
      and C57BL/6 mice, normal and leukemic.

PMID- 11947541
TI  - The postnatal development of mitochondrial tyrosine aminotransferase in rat
      liver.

PMID- 11947542
TI  - Stoicheiometry of O-demethylase activity in Pseudomonas aeruginosa.

PMID- 11947543
TI  - Elucidation by ionophores of the a DeltapH control of anion distribution across
      the mitochondrial membrane.

PMID- 11947544
TI  - The preparation of mitochondria from muscle without the use of a homogeniser.

PMID- 11947545
TI  - Erratum.

PMID- 11947547
TI  - Biological Activity of the phenylethanol and its derivatives. Influence on
      isolated DNA nucleotidyltransferase and DNAase.

PMID- 11947546
TI  - Specific incorporation of exogenous thymidine monophosphate into DNA in
      Saccharomyces cerevisiae.

PMID- 11947548
TI  - Free nucleotides in retina.

PMID- 11947549
TI  - ?
AB  - Kinetic properties of microsomal glucokinase of rat liver have been investigated.
      The enzyme is inhibited by ATP and activated or deinhibited by AMP. It displays
      properties associated with a typical allosteric enzyme which could realize a
      feedback control of glycolysis.

PMID- 11947550
TI  - ?
AB  - The pH dependence of spin-spin coupling constants J (P-O-P) of ADP and ATP has
      been determined from the phosphorus NMR spectra at 0 degrees. The variation
      curves have been interpreted as titration curves. These give different pK values.
      Comparison with the tripolyphosphate shows the existence of triphosphate chain
      structural deformation in the nucleotides.

PMID- 11947551
TI  - The distribution of 14C-proline peptides synthesized in vitro directed by
      polycytidylic acid; the effect of chloramphenicol.

PMID- 11947552
TI  - ?
AB  - Histone is able to associate with radioactive RNA to form a complex which is
      retained on a millipore filter; 500 &mgr;g of histone F(1) from bone marrow is
      able to combine with 100 &mgr;g of RNA. Chromatin acidic proteins reduce this
      association up to 50%. The binding between RNA and histone does not occur in the
      presence of urea and NaCl.

PMID- 11947553
TI  - Covalent association of thyroglobulin subunits in a thyroid polyribosomal cell
      free system.

PMID- 11947554
TI  - On a modification of the gene product P23 according to its use as subunit of
      either normal capsids of phage T4 or of polyheads.

PMID- 11947556
TI  - The effect of some proton conducting systems on protamine inhibited respiration.

PMID- 11947555
TI  - Purification of membrane fragments derived from the non excitable surface of the
      eel electroplax.

PMID- 11947557
TI  - Counter-transport between sugars and amino acids in rabbit ileum.

PMID- 11947559
TI  - Isolation of 4-amino-4-deoxy-L-arabinose from S and R form bacterial
      lipopolysaccharides.

PMID- 11947558
TI  - ?
AB  - Guinea-pig antisera to bovine insulin and proinsulin were analysed and the
      association constants and the concentrations of combining sites specific for
      insulin and for the C-chain were determined. Both antisera contained combining
      sites with higher (Ak(1) sites) and lower (Ak(2) sites) affinities for the cross
      reacting antigens.Antisera produced in response to both insulin and proinsulin
      had similar concentrations of both the more affine and less affine insulin
      specific binding sites. Bovine insulin contaminated with traces of proinsulin did
      not induce antibodies specific for the C-chain.Antisera to proinsulin contained
      equal amounts of high affinity binding sites specific for the C-chain and for the
      insulin part of the molecule. After absorption of the insulin-specific antibodies
      these sera can be used for the immunoassay of proinsulin.

PMID- 11947560
TI  - High biological activity in chloroplasts from Euglena gracilis prepared with a
      new gas pressure device.

PMID- 11947561
TI  - Purification of soluble murine transplantation antigens by isoelectric focusing.
AB  - Hydrosoluble transplantation antigens were prepared from membranes and microsomes
      of C(3)H mice (BP8 tumoral cells) and purified by isoelectric focusing. A
      biologically active fraction which seems homogenous by acrylamide gel
      electrophoresis was characterized: it specifically inhibits anti C(3)H
      hemagglutinin antibodies and provokes a highly significant prolongation of skin
      graft.

PMID- 11947562
TI  - The inhibition of trypsin, plasmin, and thrombin by benzyl 4-guanidinobenzoate
      and 4'-nitrobenzyl 4-guanidinobenzoate.
AB  - The inhibition of the enzymes trypsin, plasmin, and thrombin by benzyl 4
      guanidinobenzoate and 4'-nitrobenzyl 4-guanidinobenzoate is caused by acylation
      of the active site. Second order rate constants were determined.

PMID- 11947563
TI  - A flash-induced reaction of a synthetic light-sensitive substrate with alpha
      chymotrypsin.

PMID- 11947564
TI  - Aspartic acid residue no. 177 of bovine trypsinogen.

PMID- 11947566
TI  - Polyphosphate groups at the 5'-ends of nuclear dRNA fractions.

PMID- 11947565
TI  - A computer program for the determination of kinetic parameters from sigmoidal
      steady-state kinetics.

PMID- 11947568
TI  - Characterization of an acidic protein in 50 s ribosomes of E. coli.

PMID- 11947567
TI  - ?
AB  - The turnover of terminal AMP of rat liver tRNA relative to that of internal AMP
      was studied in presence of various inhibitors. Actinomycin D and aflatoxin B(1),
      which strongly depress transcription in liver, lead to an increase of the
      specific radioactivity of external AMP/specific radioactivity of internal AMP
      ratio. On the contrary, drugs which inhibit the in vivo incorporation of
      aminoacids determine a significant decrease of this ratio.

PMID- 11947569
TI  - Ribosomal proteins. Secondary structure of individual ribosomal proteins of E.
      coli studied by circular dichroism.

PMID- 11947570
TI  - Polarized fluorescence of acridine orange-transfer RNA complexes.

PMID- 11947571
TI  - Unprimed synthesis of polymers with RNA-polymerase.

PMID- 11947572
TI  - Determination of amino acid sequences in peptides by mass spectrometry.
      Desulfurization of sulfur-containing peptides.

PMID- 11947573
TI  - ?
AB  - The energy-independent K(+)-H(+)-exchange was measured in intact mitochondria and
      submitochondrial particles at different K(+)-concentration of the incubation
      medium. Correlation was found between H+-displacement and specific activity of
      monoamine oxidase. It is concluded, that the energy-independent K(+)-H(+)
      exchange is localized in the outer membrane of mitochondria.

PMID- 11947575
TI  - Active complex formation in cell-free extracts programmed by polyuridylic acid
      samples of different average chain length.

PMID- 11947574
TI  - Enzymatic deficiency in neurological mutants. Brain uridine diphosphate
      galactose: Ceramide galactosyl transferase in jimpy mouse.

PMID- 11947576
TI  - Adenylate kinase in the interconversion of adenine nucleotides in muscle cytosol.

PMID- 11947577
TI  - Structural features of the beta-glucans enzymatically synthesized from uridine
      diphosphate glucose by wheat seedlings.

PMID- 11947579
TI  - Errata.

PMID- 11947578
TI  - The effect of tetranitromethane on the activity of anti-tobacco mosaic virus
      antibodies.

PMID- 11947580
TI  - The specificity of inhibition of DNA-dependent RNA polymerase by Bacillus
      thuringiensis exotoxin.

PMID- 11947582
TI  - Poly U-dependent ribosomal binding of Lys-tRNA(Lys).

PMID- 11947581
TI  - Dissociation and reconstitution of active DNA-dependent RNA-polymerase from E.
      coli.

PMID- 11947583
TI  - Inhibition of enzymically active N-acetyl-homocysteinyl-ribonuclease by silver
      ions.

PMID- 11947584
TI  - Changes of the chlorophyll-spectrum in living chlorella, if the photolyte is
      split by light.

PMID- 11947585
TI  - Effect of cycloheximide on the reaction of puromycin with polysome-bound peptidyl
      tRNA.

PMID- 11947586
TI  - Deoxyribonuclease I covalently coupled to porous glass.

PMID- 11947587
TI  - Specificity of alpha-chymotrypsin. Dipeptide substrates.

PMID- 11947588
TI  - Specificity of alpha-chymotryspin.

PMID- 11947589
TI  - The beta-chain of frog hemoglobin (Rana esculenta). A 34 residue N-terminal
      sequence.

PMID- 11947590
TI  - Partial amino acid sequence of the variable region of a mouse gammaG2a
      immunoglobulin heavy chain. Evidence for the existence of a third sub-group of
      variability for the heavy chain pool.

PMID- 11947591
TI  - Sequence of N-terminal 46 amino acid residues in pig immunoglobulin lambda
      chains.

PMID- 11947592
TI  - Effect of modification of lysine residues of cow colostrum trypsin inhibitor on
      its antitryptic and antichymotryptic activity.

PMID- 11947593
TI  - Solubilization of the membrane bound lactose specific component of the
      staphylococcal PEP dependant phosphotransferase system.
AB  - The membrane bound lactose specific component of the PEP dependant
      phosphotransferase system of Staphylococcus aureus has been solubilized using the
      non ionic detergent Triton X-100. Some properties of the crude soluble enzyme are
      reported.

PMID- 11947594
TI  - Effect of non-haem iron proteins and cytochrome C from Azotobacter upon the
      activity and oxygen sensitivity of Azobacter nitrogenase.

PMID- 11947595
TI  - Spin probes for binding site polarity.

PMID- 11947596
TI  - A Microdetermination of cyclic AMP based upon activation of a liver protein
      kinase.

PMID- 11947597
TI  - Studies on O-specific polysaccharides of Shigella flexneri 1b(I) and its smooth
      mutant Z(III).

PMID- 11947598
TI  - Redox transitions of cytochromes and pyridine nucleotides upon stimulation of an
      isolated rat ganglion.

PMID- 11947599
TI  - Enzymic N-acetylation of a sulfur analog of L-lysine, S-(beta-aminoethyl)-L
      cysteine.

PMID- 11947600
TI  - The synthesis of one-carbon units from CO(2) via a new ferredoxin dependent
      monocarboxylic acid cycle.

PMID- 11947601
TI  - Pyridine nucleotide-dependent dehydrogenases a report of an advanced study
      Institute held at the University of Konstanz, Germany, September 15-20, 1969.

PMID- 11947602
TI  - Selective repression of benzoate or tryptophan mediated induction of liver
      tyrosine aminotransferase by phentolamine in adrenalectomized rats.

PMID- 11947603
TI  - The influence of alpha(2)-macroglobulin on the elastolytic and esterolytic
      activity of elastase.

PMID- 11947604
TI  - Acylglucoses in Escherichia coli, Saccharomyces cerevisiae and Agaricus bisporus.

PMID- 11947605
TI  - Inhibition of succinate oxidation and transport into mitochondria by metal
      complexing agents.

PMID- 11947606
TI  - 35S-Atractyloside binding affinity to the inner mitochondrial membrane.
AB  - Isolated inner mitochondrial membrane contains a small number of binding sites
      for atractyloside (of the order of 0.1 nmole/mg of protein) with very high
      binding affinity (half saturation at 0.014 &mgr;M atractyloside). The high
      affinity binding ability of the inner mitochondrial membrane is markedly
      decreased upon aging, acidification of the medium or addition of ADP, but remains
      unchanged in the presence of uncouplers such as FCCP. Added ADP causes a two-step
      transition from the high affinity binding to low affinity binding (K(d) > 0.50
      &mgr;M) and concomitantly a significant increase of the measured number of
      binding sites (about a doubling). The half maximum effect in the first step
      transition is given by 1 &mgr;M ADP. The use of 35S-atractyloside as a probe of
      the inner mitochondrial membrane conformation specifically related to the adenine
      nucleotide translocation is discussed.

PMID- 11947607
TI  - Spectroscopic resolution of the "iron-flavoprotein trough" of the respiratory
      chain of submitochondrial particles from Torulopsis utilis.

PMID- 11947608
TI  - Increased yield of ribosome dimers from the rat seminal vesicle following
      castration.

PMID- 11947609
TI  - A mild procedure for the fractionation of ox erythrocyte membrane proteins.

PMID- 11947610
TI  - Reversible dinitrophenylation of glyceraldehyde 3-phosphate dehydrogenase.
      Identification of the labeled site.

PMID- 11947611
TI  - The natural release of nucleic acids from bacteria into plant cells and the
      transcription of host cell DNA.

PMID- 11947612
TI  - Effect of sialidase on blood group specificity of hog submaxillary glycoproteins.
AB  - Hogs can be divided into three phenotypes A, H and In, depending on the ability
      of extracts of their submaxillary glands to inhibit the agglutination of human A
      cells with human anti-A, and human O cells with eel-anti-H serum. Evidence is
      here provided that the inactive glycoprotein, In, represents H active
      glycoprotein containing additional N-glycolyl neuraminic acid, which
      stereospecifically masks the H determinant, alpha (1 --> 2)-L-fucosyl residue.

PMID- 11947613
TI  - Tay-sachs disease and related disorders: Fractionation of brain N-acetyl-beta
      hexosaminidase on DEAE-cellulose.

PMID- 11947614
TI  - Countercurrent distribution of the supernatant of incubated glomeruli.

PMID- 11947616
TI  - Evidence for two antigenic determinants in the C-terminal region of rat skin
      collagen.

PMID- 11947615
TI  - The preparation of glucose oxidase chemically attached to polystyrene and its use
      in the automated analyses of glucose.

PMID- 11947617
TI  - The influence of alanine on the glutamate/oxoglutarate x NH(+)(4) ratio in the
      guinea-pig liver.

PMID- 11947618
TI  - Decreased stability of rat liver polyribosomes after gel filtration on sephadex.

PMID- 11947619
TI  - The subunits of bovine thyrotropin. Their isolation and comparison with the
      subunits of Luteinizing hormone.

PMID- 11947621
TI  - Properties and regulatory effect on tetrapyrrole biosynthesis of succinyl CoA
      synthetase isolated from soybean callus tissue system.

PMID- 11947620
TI  - A new intermediate in the biosynthesis of thiamine.

PMID- 11947622
TI  - Tentative sequence of 52 amino acid residues from the constant part of pig
      immunoglobulin (kappa) chains.

PMID- 11947623
TI  - Familial diphosphoglyceratemutase deficiency. Influence on the oxygen affinity
      curves of hemoglobin.

PMID- 11947624
TI  - Separation of two forms of cytochrome P450 adrenal cortex mitochondria.
AB  - The separation of two distinct forms of cytochrome P450 from adrenal cortex
      mitochondria has been achieved by the following steps; (1) lyophilisation (2) iso
      octane extraction, (3) (NH(4))(2)SO(4) fractionation in the presence of sodium
      cholate. The fraction precipitating between 25-35 percent (NH(4))(2)SO(4) gave a
      difference spectrum with 11-deoxycorticosterone (11-DOC) but not with 20alpha
      hydroxycholesterol (20alpha-HOC). This fraction showed high 11beta-hydroxylase
      activity but low activity for side chain cleavage of cholesterol (S.C.C.). The
      fraction precipitating between 45-60 percent (NH(4))(2)SO(4) gave a difference
      spectrum with 20alpha-HOC but not with 11-DOC and exhibited high S.C.C. activity
      but low 11beta-hydroxylase activity. The absorption spectrum of the 45-60 percent
      fraction indicated a preponderance of high spin hemoprotein (lambda(max) 395 nm).

PMID- 11947625
TI  - Hydrolysis of fucoidan by abalone liver alpha-L-fucosidase.

PMID- 11947626
TI  - The restricted reactivity of the side-chain amino groups of collagen toward
      formaldehyde.

PMID- 11947627
TI  - Circular dichroism of bilirubin-human serum albumin complexes in aqueous
      solution.

PMID- 11947628
TI  - Erratum.

PMID- 11947629
TI  - Chromatographic and electrophoretic evidence for several sugar dehydrogenases in
      mammalian liver.

PMID- 11947630
TI  - The effect of cobalt on the synthesis of globin and haem in reticulocytes.

PMID- 11947631
TI  - Hydrolysis of L-3-benzyl-2,5-diketomorpholine by chymotrypsin.

PMID- 11947632
TI  - Substrate activation by non-covalent binding in the active site of chymotrypsin.

PMID- 11947633
TI  - Electron spin resonance investigations of methyl hydrogen peroxide compound II of
      catalase.

PMID- 11947634
TI  - Transient time of the pyruvate kinase-lactate dehydrogenase system of rabbit
      muscle in vitro.

PMID- 11947636
TI  - Evidence for two regions in the polysaccharide moiety of the lipopolysaccharide
      of Pseudomonas aeruginosa 8602.

PMID- 11947635
TI  - The presence of beta-structure in concanavalin A.

PMID- 11947637
TI  - Incomplete conversion of glycogen and starch by crystalline amyloglucosidase and
      its importance in the determination of amylaceous polymers.

PMID- 11947638
TI  - Affinity of antamanide for sodium ions.

PMID- 11947639
TI  - Studies on the mechanism of CCl(4)-induced polyribosomal damage.

PMID- 11947640
TI  - Dissociation of Escherichia coli 70 S ribosomes with enzymatic digestion.

PMID- 11947641
TI  - The inhibition of ribonucleic acid synthesis by the thiol-oxidizing agent,
      diamide, in Escherichia coli.
AB  - The thiol-oxidizing agent, diamide, has been used to convert glutathione to
      glutathione disulfide within the cells of a stringent strain of Escherichia coli
      (CP 78), leading to a cessation of 14C-leucine incorporation (protein synthesis)
      and 3H-uracil incorporation (RNA synthesis). Parallel experiments with an
      isogenic relaxed strain (CP 79) gave similar results, providing evidence that
      glutathione is closely linked to RNA synthesis indepently of the link previously
      shown to protein synthesis.

PMID- 11947642
TI  - Inhibition by alpha-amanitin of induction of tyrosine transaminase in rat liver
      by cortisol.

PMID- 11947643
TI  - Induction of liver tyrosine aminotransferase by theophylline and its repression
      by phentolamine and glucose in adrenalectomized rats.

PMID- 11947644
TI  - Isolation and characterization of in vitro radioactively labelled sh-proteins
      from rat liver mitochondrial membranes.

PMID- 11947645
TI  - A novel reactivity of papain and a convenient active site titration in the
      presence of other thiols.

PMID- 11947646
TI  - Relationship between molecular weight and area of protein films immobilized on
      PVC membranes.

PMID- 11947647
TI  - A factor of protein character in rat liver inhibiting lipase activity of rat
      pancreas.

PMID- 11947649
TI  - Methods for the evaluation of ideal molecular weights from single sedimentation
      equilibrium experiments.

PMID- 11947648
TI  - Inter-strand cross-linkages occurring in the photoreaction between psoralen and
      DNA.

PMID- 11947650
TI  - Errata.

PMID- 11947652
TI  - On the specificity of starch debranching enzymes.

PMID- 11947651
TI  - Membrane aspects of the immune response. Report of a workshop held in Titisee,
      Schwarzwald, Germany, October 13-15, 1969.

PMID- 11947653
TI  - A low buoyant density active complex for proteosynthesis in mouse plasmocytoma
      cells.

PMID- 11947654
TI  - The effect of temperature on the biosynthesis of chondroitin 4-sulphate in
      cartilage slices in vitro.

PMID- 11947655
TI  - Antigenic determinants of two components of proteoglycan complex from bovine
      cartilage.
AB  - The immunological properties of a glycoprotein fraction and of proteoglycan
      subunits obtained from bovine nasal cartilage by nondisruptive methods of
      isolation have been studied. Using the techniques of hemagglutination and
      hemagglutination inhibition, we found that the glycoprotein contains most of the
      species-specific determinants, whereas the proteoglycan subunits contain most of
      the cross-reacting ones.

PMID- 11947656
TI  - Evidence for a slow transition leading to cooperative binding of 5'-amp onto
      rabbit muscle phosphorylase b at 5 degrees.

PMID- 11947657
TI  - Structural and functional role of FAD in the NADH-nitrate reducing system from
      Chlorella.

PMID- 11947658
TI  - Effect of cholesteryl esters with different saturated fatty acids on aminoacyl
      tRNA synthesis in rat liver.

PMID- 11947659
TI  - Complexes of the tryptophanyl tRNA synthetase with adenosinetriphosphate and
      tryptophanyladenylate.

PMID- 11947660
TI  - The nucleotide sequence of a leucine transfer RNA from E. coli.

PMID- 11947661
TI  - The effects of the rifamycin antibiotics on algae.

PMID- 11947662
TI  - Mechanism of mutagenesis by N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) V.
      Methylation of DNA by N-trideuteriomethyl-N'-nitro-N-nitroso-guanidine (D(3)
      MNNG).

PMID- 11947664
TI  - Negative homotropic kinetics of soybean callus porphobilinogen deaminase
      uroporphyrinogen III cosynthetase.

PMID- 11947663
TI  - Effect of prolactin on pathways of glucose oxidation in explants from rabbit
      mammary gland.

PMID- 11947665
TI  - Specificity of rat liver NAD synthetase.

PMID- 11947666
TI  - Substrate dependent heterogeneity of initiation by RNA polymerase from
      thermophilic B. megaterium.

PMID- 11947667
TI  - 81Br and 35Cl nuclear magnetic resonance studies of E. Coli alkaline phosphatase.

PMID- 11947668
TI  - In vitro effects of polyvinylpyrrolidone on the enzymatic action of pepsin.

PMID- 11947669
TI  - Phytohemagglutinins: A new class of metalloproteins. Isolation, purification, and
      some properties of the lectin from Phaseolus lunatus.

PMID- 11947670
TI  - The beta chain of frog hemoglobin (Rana esculenta): Amino acid sequence of
      residues 35 to 98.

PMID- 11947671
TI  - Positive increase of redox potential of the extramitochondrial NADP(H) system by
      mixed function oxidations in hemoglobin-free perfused rat liver.

PMID- 11947672
TI  - Proteins of rat brain myelin. Extraction with sodium dodecylsulphate and
      electrophoresis on analytical and preparative scale.

PMID- 11947673
TI  - Fractionation of translation initiation factor B (F3) into cistron-specific
      species.

PMID- 11947674
TI  - Role of initiation factor B (F3) in the preferential translation of T4 late
      messenger RNA in T4 infected E. Coli.

PMID- 11947675
TI  - The 3'-terminal nucleotide sequence (n = 16) of bacteriophage MS2 RNA.

PMID- 11947676
TI  - Influence of serum albumin on the activity of a microsomal aminopeptidase.

PMID- 11947677
TI  - Isolation and characterization of the cyanogen bromide peptides from the alpha2
      chain of calf skin collagen.

PMID- 11947678
TI  - Cycloheximide-resistant amino acid incorporation into rat liver mitochondrial
      proteins in vivo.

PMID- 11947679
TI  - Mass spectrometry of peptide derivatives. Temporary protection of methionine as
      sulfoxide during permethylation.

PMID- 11947680
TI  - On the use of tetranitromethane as a nitration reagent for tyrosyl residues.

PMID- 11947681
TI  - Role of non-histone components in determining organ specificity of rabbit
      chromatins.

PMID- 11947682
TI  - Parameter estimation and enzyme kinetic models.

PMID- 11947683
TI  - Aminoacyl-tRNA synthetase formation and cell division in bacteria.

PMID- 11947684
TI  - Ultraviolet absorption spectrum of RNA polymerase.

PMID- 11947685
TI  - Amanitin binding to calf thymus RNA polymerase B.

PMID- 11947686
TI  - Optical properties of chemically synthetised polynucleotides containing D- or L
      ribonucleosides.

PMID- 11947687
TI  - Thiaminepyrophosphate induced changes in the optical activity of baker's yeast
      transketolase.

PMID- 11947688
TI  - Sialoglycoproteins, gangliosides and related enzymes in developing rat brain.

PMID- 11947689
TI  - Glyoxylate inhibition of clostridial pyruvate synthase.

PMID- 11947690
TI  - Oligomycin and ADP sensitivity of in vitro alkylation of SH-groups in rat liver
      mitochondria.

PMID- 11947691
TI  - The effect of cobalt chloride on serum protein electrophoretic patterns in mice.

PMID- 11947692
TI  - Absence of interaction between concanavalin a and heparin or heparin sulfate.

PMID- 11947693
TI  - Localisation de l'activite phospholipasique dans les tissus vegetaux. 1) Sur
      l'absence d'activite phospholipasique D dans les mitochondries et les plastes
      isoles.
AB  - Mitochondria and plastids isolated from various plant tissues by methods which
      exclude contamination by other cell organelles lack phospholipase D activity.

PMID- 11947694
TI  - Retinol: A fluorescent probe for membrane lipids.

PMID- 11947695
TI  - An improved method for preparing brain cell suspensions.

PMID- 11947696
TI  - Allosteric properties of yeast pyruvate decarboxylase.

PMID- 11947697
TI  - Purification of lactose synthetase a protein from human milk and demonstration of
      its interaction with alpha-lactalbumin.
AB  - A fairly simple procedure for isolating lactose synthetase A protein from human
      milk in 36% yield is described. The A protein has a molecular weight of about
      40,000. Its interaction with alpha-lactalbumin in the presence of N
      acetylglucosamine has been demonstrated by affinity chromatography and gel
      filtration.

PMID- 11947699
TI  - Errata.

PMID- 11947698
TI  - Amino and carboxy-terminal sequences of neocarzinostatin, an anti-tumor
      polypeptide antibiotic.

PMID- 11947700
TI  - Aurovertin-sensitive phosphate activation of mitochondrial adenosine
      triphosphatase.

PMID- 11947702
TI  - The stimulation of post-illumination ATP synthesis by valinomycin.

PMID- 11947701
TI  - Protective effect of ammonia on mitochondrial structure and respiration.

PMID- 11947703
TI  - Effect of insulin on adenylate kinase activity and glycolysis rate of the
      isolated rat diaphragm in the absence of added glucose.

PMID- 11947704
TI  - A pH dependent alteration of photosystem II activity in tris washed chloroplasts.

PMID- 11947705
TI  - On the presence of a dense internal region in the 50 S subparticle of E. coli
      ribosomes.

PMID- 11947706
TI  - Differences in binding of oligo C to charged and uncharged tRNA.

PMID- 11947707
TI  - Interaction of haemoglobin messenger RNP with the small subparticle of
      reticulocyte ribosomes.

PMID- 11947708
TI  - Stereochemistry of the oxidation at the alpha carbon of butyryl-CoA and of the
      enzymic hydrogen exchange.

PMID- 11947709
TI  - Cerebroside sulfate-amine interaction in neoplastic mast cells.

PMID- 11947710
TI  - Characterization of an acetyl group at the N-terminal position of alpha-amylase
      by nuclear magnetic resonance spectroscopy.

PMID- 11947711
TI  - Relationship between red blood cell agglutination and polysaccharide
      precipitation by phytohemagglutinin of Pisum sativum L.

PMID- 11947712
TI  - Inhibition of cathepsin E by diazoacetyl-norleucine methyl ester.

PMID- 11947713
TI  - Occurrence of a high amount of glycerylphosphorylcholine in Ascaris lumbricoides.

PMID- 11947892
TI  - Vascular effects of dietary L-arginine supplementation.
AB  - The vascular endothelium is acknowledged to play an important role in vascular
      physiology. Attention has focused on endothelial production of nitric oxide as a
      key element in many of the processes associated with the development of
      atherosclerosis. L-arginine is the substrate for the enzyme nitric oxide synthase
      (NOS), which is responsible for the endothelial production of nitric oxide.
      Therefore, many investigators have been interested in whether dietary L-arginine
      supplementation can augment nitric oxide production and thereby improve vascular
      health. The effects of oral L-arginine on vascular health and disease have been
      examined both in human beings and in various animal models. In this review, we
      summarize the results of studies of oral L-arginine supplementation on
      atherosclerotic lesion formation, as well as markers of endothelial function
      (e.g. macrophage function, platelet aggregation and adhesion, and in vitro
      vascular ring studies). Although results of oral L-arginine supplementation in
      hypercholesterolemic animals have generally shown beneficial effects, the data in
      humans are varied, possibly because of small sample sizes and brief periods of
      study. Long-term randomized clinical trials are needed to more definitively
      address whether oral L-arginine supplementation could be advantageous for
      vascular health.

PMID- 11947893
TI  - Relation of the -514C/T polymorphism in the hepatic lipase gene to serum HDL and
      LDL cholesterol levels in postmenopausal women under hormone replacement therapy.
AB  - Hepatic lipase (HL) is a lipolytic enzyme that catalyzes hydrolysis of
      triglycerides and phospholipids in all major classes of lipoproteins. Recently, a
      -514C/T polymorphism in the promoter region of the HL gene was found to be
      associated with variations in hepatic lipase activity and serum high density
      lipoprotein cholesterol (HDL-C) levels. Postmenopausal hormone replacement
      therapy (HRT) has known favorable effects on serum lipid and lipoprotein levels.
      In this study, we examined the relation between the -514C/T polymorphism and
      serum lipid and lipoprotein levels in postmenopausal women prior to and after 3
      months of HRT. Significant associations between the -514 C/T polymorphism and HDL
      C, low density lipoprotein cholesterol (LDL-C) and apolipoprotein A-I (apo A-I)
      levels were observed before and/or after 3 months of HRT. With HRT, serum total
      cholesterol (TC), LDL-C and apolipoprotein B (apo B) levels were reduced
      significantly (P=0.0001), and HDL-C and apo A-I levels were increased
      significantly (P=0.0001). However, the degrees of change in lipid and lipoprotein
      levels due to HRT did not differ significantly between the HL genotypes.

PMID- 11947894
TI  - Anti-atherosclerotic effect of simvastatin depends on the presence of
      apolipoprotein E.
AB  - Low density lipoprotein receptor deficient (LDLR-KO) and apolipoprotein E
      deficient (apo E-KO) mice both develop hyperlipidemia and atherosclerosis by
      different mechanisms. The aim of the present study was to compare the effects of
      simvastatin on cholesterol levels, endothelial dysfunction, and aortic lesions in
      these two models of experimental atherosclerosis. Male LDLR-KO mice fed a high
      cholesterol (HC; 1%) diet developed atherosclerosis at 8 months of age with
      hypercholesterolemia. The addition of simvastatin (300 mg/kg daily) to the HC
      diet for 2 more months lowered total cholesterol levels by approximately 57% and
      reduced aortic plaque area by approximately 15% compared with the LDLR-KO mice
      continued on HC diet alone, P<0.05. Simvastatin treatment also improved
      acetylcholine (ACh)-induced endothelium-dependent vasorelaxation in isolated
      aortic rings, which was associated with an increase in NOS-3 expression by
      approximately 88% in the aorta measured by real time polymerase chain reaction
      (PCR), P<0.05. In contrast, in age-matched male apo E-KO mice fed a normal diet,
      the same treatment of simvastatin elevated serum total cholesterol by
      approximately 35%, increased aortic plaque area by approximately 15%, and had no
      effect on endothelial function. These results suggest that the therapeutic
      effects of simvastatin may depend on the presence of a functional apolipoprotein
      E.

PMID- 11947895
TI  - Comparison of apolipoprotein B metabolism in familial defective apolipoprotein B
      and heterogeneous familial hypercholesterolemia.
AB  - Both defective LDL receptors (familial hypercholesterolaemia, FH) and mutations
      in apolipoprotein B (apoB) on LDL (familial defective apoB, FDB) give rise to a
      phenotype of elevated LDL cholesterol. We sought to compare the metabolic basis
      of the two conditions by examining apoB turnover in FDB and FH subjects. A group
      comprising three heterozygous and one homozygous FDB subjects were compared with
      five FH heterozygotes and 17 control subjects using a deuterated leucine tracer.
      Kinetic parameters were derived by multicompartmental modelling. FH heterozygotes
      had a reduced delipidation rate for VLDL, which led to a moderate increase in
      plasma triglyceride. Compared with controls and FH, the FDB subjects converted
      44% less IDL to LDL. The LDL FCR was reduced to a similar extent in FDB and FH.
      In all subjects LDL plasma levels appeared to be regulated by the LDL FCR and the
      rate of production of small VLDL. We conclude that disturbances in IDL metabolism
      provide the basis for understanding why FDB is less severe than FH. Our findings
      suggest that an apoB-LDL receptor interaction is important in the IDL to LDL
      conversion.

PMID- 11947896
TI  - Effects of VasoCare therapy on the initiation and progression of atherosclerosis.
AB  - VasoCare therapy, which involves the administration of autologous blood following
      the ex vivo exposure to physico-chemical stressors, has been shown to modulate
      immune responses. Since immune mechanisms have been recognized to be pivotal in
      the pathogenesis of atherosclerosis, we hypothesized that VasoCare treatment
      would inhibit atherosclerosis in LDL-R (-/-) mice. Three groups of LDL-R (-/-)
      mice were studied: a control group that was fed normal chow (Group I) and no
      other treatment; a control group that received a high cholesterol (HC) diet for 8
      weeks (group II) with sham saline injections; and a third group (III) that
      received HC diet for 8 weeks and VasoCare treatment initiated after four weeks of
      HC feeding. Atherosclerotic area (AA), relative to total aortic area (TA), was
      assessed after 8 weeks of HC feeding by oil red O staining, and cross sectional
      plaque area at the level of the aortic valve leaflets was determined by
      quantitative morphometry. HC mice exhibited substantial aortic lipid deposition
      which was profoundly reduced in the VasoCare treated animals (AA/TA ratios in
      group II: 0.32+/-0.15 vs. group III: 0.17+/-0.06; P<0.05). This was associated
      with a significant decrease in cross sectional area of plaque in the aortic
      sinuses. VasoCare therapy also reduced the xanthoma formation and limb swelling
      characteristic of this animal model. However, cholesterol levels, measured by an
      enzymatic assay, showed similar marked increases in total serum cholesterol (CHO)
      in the animals receiving HC diet alone and those receiving the HC diet and
      VasoCare treatment [group I: 5.4+/-0.8 mM, group II: 46.7+/-3.6 mM, and group
      III: 44.7+/-2.8 mM (P<0.01 vs. group I)]. We conclude that VasoCare treatment
      inhibits progression of atherosclerotic lesions in a murine model of human
      familial hypercholesterolemia by a mechanism independent of cholesterol lowering.

PMID- 11947897
TI  - Purinergic receptor distribution in endothelial cells in blood vessels: a basis
      for selection of coronary artery grafts.
AB  - Expression levels of the purinergic P2X receptor subunits (P2X(1) to P2X(7)) and
      P2Y(2) were examined in the endothelial cell layer of internal mammary artery
      (Ann. Thorac. Surg. 54 (1992) 652), radial artery (Ann. Thorac. Surg. 16 (1973)
      111) and saphenous vein (Ann. Thorac. Surg. 20 (1975) 628) samples obtained at
      surgery for coronary artery bypass grafts using immunohistochemistry and confocal
      microscopy. Similar levels of P2X(1), P2X(2), P2X(3), P2X(7) and P2Y(2) were
      found in the endothelial cells in all vessels examined while the levels of P2X(5)
      and P2X(6) were uniformly lower. A clear difference was measured in P2X(4)
      expression between arteries and veins. Both radial and internal mammary arteries
      exhibited very low levels of P2X(4) whereas the level in the saphenous vein was
      14.6 fold higher (P<0.0001), approaching that of the major receptor subtypes.
      These data showing strong expression of P2X(4) in veins have implications for the
      choice of vessels used in coronary artery bypass grafts given that P2X(4) is
      involved in calcium influx into endothelial cells, modulates blood vessel
      contractility and is up-regulated in situations involving intima proliferation
      suggesting vein grafts are more susceptible to developing atherosclerosis.

PMID- 11947898
TI  - The urokinase receptor mediates basic fibroblast growth factor-dependent smooth
      muscle cell migration through baboon aortic explants.
AB  - The urokinase receptor is required for vascular smooth muscle cell migration in
      vitro, but may not be needed in vivo since smooth muscle cell migration and
      intimal hyperplasia after arterial injury in mice are not affected by urokinase
      receptor gene deletion. We have used baboon aortic explants as a bridge between
      cell culture and in vivo experiments to determine if the urokinase receptor is
      required for smooth muscle cell proliferation and smooth muscle cell migration in
      primate vessels. Levels of urokinase receptor in explants increased with time
      after explantation, while blockade of urokinase receptor with an antibody
      decreased smooth muscle cell proliferation and smooth muscle cell migration from
      the explants. A blocking antibody to basic fibroblast growth decreased levels of
      urokinase and urokinase receptor in explants, and it decreased smooth muscle cell
      migration and mitogenesis. These results suggest that the factor urokinase
      receptor plays a positive role in smooth muscle cell migration and proliferation
      in injured primate arterial tissue, in part mediating the pro-migratory and
      proliferative effects of basic fibroblast growth factor released by damaged
      smooth muscle cells.

PMID- 11947899
TI  - Vascular proliferation and transforming growth factor-beta expression in pre- and
      early stage of diabetes mellitus in Otsuka Long-Evans Tokushima fatty rats.
AB  - The roles of transforming growth factor (TGF)-beta 1 in vascular proliferation,
      atherosclerosis, and plaque still remain controversial. TGF-beta 1 has been
      previously reported to inhibit the proliferation and migration of vascular smooth
      muscle cells and endothelial cells, in vitro. On the other hand, administration
      or transgenic overexpression of TGF-beta 1 enhances extracellular matrix
      synthesis and cellular hyperplasia of the intima and media in the normal artery
      and injured artery in vivo. We evaluated the correlation of arterial
      proliferation with plasma levels of TGF-beta 1 and TGF-beta receptor type II,
      respectively, in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a new strain of
      spontaneous non-insulin-dependent diabetes mellitus (NIDDM) models. OLETF rats
      (n=30) were divided into three groups aged 5,15, and 30 weeks. Long-Evans
      Tokushima Otsuka (LETO) rats (n=30) were used as age-matched non-diabetic
      controls. Plasma TGF-beta1 and insulin were determined by enzyme-linked
      immunosorbent assay. Immunoreactive TGF-beta receptor type II antigen was
      detected by immunohistochemistry on the thoracic artery. Arterial media area was
      measured microscopically. Oral glucose tolerance test was performed to examine
      the stage of diabetes mellitus. The thoracic aorta wall section area increased
      significantly from the age of 15 weeks in OLETF rats, versus LETO rats. In both
      OLETF and LETO rats, plasma TGF-beta 1 increased significantly from the age of 15
      weeks. In OLETF rats, plasma TGF-beta 1 increased significantly over that in LETO
      rats (P<0.001). Furthermore, TGF-beta receptor type II was detected on aortic
      wall as strong signals in OLETF rats, but only weakly in LETO rats. OLETF rats
      showed hyperinsulinemia and insulin resistance from the age of 15 weeks. With
      oral glucose tolerance test, from the age of 15 weeks, the high glucose level in
      OLETF rats was prolonged to 2 h after loading, and the insulin levels at both
      fasting and after loading were significantly higher than those of LETO rats
      (P<0.001). There are significant linear relations between plasma TGF-beta 1
      antigen and aorta wall section area, and plasma TGF-beta 1 antigen and fasting
      insulin level (P<0.001, respectively). We found that plasma TGF-beta 1 and
      vascular TGF-beta type II receptors existed to a greater extent in pre- and early
      stages of diabetes mellitus (DM) in OLETF rats compared with LETO rats. The
      greater extent of each in OLETF rats was associated with hyperinsulinemia and/or
      vascular thickening.

PMID- 11947900
TI  - Increased proliferation of endothelial cells with overexpression of soluble TNF
      alpha receptor I gene.
AB  - Vascular endothelial growth factor (VEGF) can overcome a potential anti
      angiogenic effect of TNF-alpha by inhibiting endothelial apoptosis induced by
      this cytokine. Soluble TNF-alpha receptor I (sTNFRI) is an extracellular domain
      of TNFRI and antagonizes the activity of TNF-alpha. Here we report that sTNFRI is
      able to stimulate the growth of endothelial cells not by antagonizing TNF-alpha.
      Exogenously added recombinant human sTNFRI stimulated significantly more cell
      growth of human umbilical venous endothelial cells (HUVEC) with a low dose (50
      200 pg/ml) compared with smooth muscle cells. In contrast, monoclonal antibody
      against TNF-alpha did not stimulate growth of human HUVEC. The sTNFRI expression
      plasmid (pcDNA3.1 plasmid) was introduced into the cell culture using OPTI-MEM,
      lipofectin and transferrin. Growth of HUVEC transfected with sTNFRI vector also
      increased significantly compared with those transfected with control vector.
      HUVEC transfected with sTNFRI vector increased the extracellular domain of TNFRI
      mRNA levels, but did not affect the intracellular domain of TNFRI mRNA levels.
      Accumulation of sTNFRI significantly increased in conditioned medium from HUVEC
      transfected with sTNFRI vector compared with those transfected with control
      vector. HUVEC transfected with sTNFRI vector not only increased sTNFRI but also
      prevented shedding of sTNFRI from TNFRI. The TNF-alpha -induced internucleosomic
      fragmentation was also significantly prevented in HUVEC transfected with sTNFRI
      vector compared with those transfected with control vector. These results suggest
      that instead of growth factors such as VEGF, local transfection of the sTNFRI
      gene may have potential therapeutic value in vascular diseases in which TNF-alpha
      is also usually highly expressed.

PMID- 11947901
TI  - Exercise training improves acetylcholine-induced endothelium-dependent
      hyperpolarization in type 2 diabetic rats, Otsuka Long-Evans Tokushima fatty
      rats.
AB  - We investigated whether endothelium-derived relaxing (EDRF) and hyperpolarizing
      factor (EDHF) is impaired in type 2 diabetic rats (Otsuka Long-Evans Tokushima
      Fatty (OLETF) rat) and whether the exercise training improves impaired EDRF and
      EDHF. Diabetic rats were divided into the sedentary and exercise-trained groups
      at the age of 16 weeks. Long-Evans Tokushima Otsuka (LETO) rats were used as age
      matched non-diabetic controls. EDRF as well as EDHF induced by acetylcholine in
      the presence of indomethacine and L-nitro N-arginine was significantly attenuated
      in the diabetic rats, and was further impaired with age. Exercise training
      significantly improved it. Both insulin resistance and abdominal fat accumulation
      were significantly greater in the diabetic rats, compared with the non-diabetic
      rats, but were decreased in exercise-trained rats. Urinary NO(2) secretion was
      decrease in the diabetic rats at each age, and it was improved by exercise
      training. The results of the study indicated that exercise training prevented
      impairment of EDHF, as well as EDRF in type 2 diabetic rats, presumably due to
      improvement of hyperglycemia and insulin resistance and increase in the
      production of nitric oxide by exercise training.

PMID- 11947903
TI  - VLDL receptor deficiency enhances intimal thickening after vascular injury but
      does not affect atherosclerotic lesion area.
AB  - The very low density lipoprotein receptor (VLDLR) has been shown to modulate cell
      migration and foam cell formation in vitro. This suggests a role for the VLDLR in
      vascular pathology associated with intimal thickening and atherogenesis. In the
      present paper both intimal thickening and atherosclerosis were studied using
      VLDLR knockout and transgenic mouse models. The role of the VLDLR in intimal
      thickening was established in an in vivo model for vascular injury. A non
      restrictive cuff was placed around the femoral artery of VLDLR deficient (VLDLR-/
      ), heterozygous deficient (VLDLR+/-) and wild type (WT) mice. Intimal thickening
      was assessed after 3 weeks by determining the intima to media (I/M) volume ratio.
      Both VLDLR-/- (I/M ratio 42%) and VLDLR+/- (I/M ratio 40%) mice showed a
      significant increase as compared with WT littermates (I/M ratio 25%). The effect
      of VLDLR deficiency on atherosclerosis was examined in VLDLR-/- mice on an LDLR
      deficient (LDLR-/-) background. In addition, we assessed whether increased
      endothelial VLDLR expression levels affect atherosclerotic lesion formation.
      Therefore, atherosclerosis was studied in LDLR deficient mice that over express
      the VLDLR in endothelial cells (PVL, LDLR-/-). Both VLDLR deficiency and
      endothelial VLDLR over expression did not affect the atherosclerotic lesion size.
      Interestingly, VLDLR-/-, LDLR-/- mice showed a high incidence of necrosis in both
      fatty streaks and atherosclerotic plaques as compared with LDLR-/- mice (75 vs.
      0% and 76 vs. 45%, respectively). In conclusion, deficiency for the VLDLR
      profoundly increased intimal thickening after vascular injury.

PMID- 11947902
TI  - Nitric oxide prevents oxidised LDL-induced p53 accumulation, cytochrome c
      translocation, and apoptosis in macrophages via guanylate cyclase stimulation.
AB  - BACKGROUND: Oxidatively modified low density lipoprotein (OxLDL) induces
      apoptosis in vascular cells including macrophages, while NO exerts antiapoptotic
      effects. Here we studied the impact of nitric oxide (NO) on OxLDL-induced
      cytochrome c release, apoptosis, and expression of the proapoptotic p53 in
      macrophages. METHODS: Human LDL was oxidised by Cu(2+), and monocytes were
      prepared from human buffy coats. Differentiation to macrophages was achieved by
      culturing cells in the presence of human serum and was followed by detecting
      monocyte chemoattractant protein 1 (MCP-1) expression (RT-PCR). Cytochrome c
      release and p53 expression of macrophages were detected by immunoblotting, and
      apoptosis by visualisation of nuclear condensation. RESULTS: OxLDL dose
      dependently (50-200 microg/ml) induced cytochrome c release that was prevented by
      preincubation with the NO-donor S-nitrosoglutathione (GSNO) (100 microM) or with
      the cGMP analogue 8-br-cGMP (100 microM) for 15 h. In cells co-treated with GSNO
      and the soluble guanylate cyclase (sGC) inhibitor oxadialoquinoxalione (ODQ, 10
      microM, 15 h), OxLDL-evoked cytochrome c release remained effective, indicating
      that NO acted via sGC-dependent cGMP formation. Parallel incubation of
      macrophages with 8-br-cGMP (100 microM) and ODQ (10 microM) for 15 h left the
      protective effect of 8-br-cGMP unaltered. Short pre-incubation (30 min) with GSNO
      or 8-br-cGMP was ineffective in preventing OxLDL-elicited cytochrome c release.
      Initiation of cytochrome c release in macrophages was paralleled by a dose
      dependent accumulation of the proapoptotic factor p53, and by enhanced rate of
      nuclear condensation. Stabilisation of p53 was prevented by preincubation with
      the NO-donor GSNO or 8-br-cGMP, thus implying a downmodulatory effect of cGMP on
      pathways that upregulate the tumor suppressor p53. CONCLUSIONS: OxLDL induces
      cytochrome c release and apoptosis in human macrophages in close association with
      p53 accumulation. NO attenuates OxLDL-induced cytochrome c release and p53
      accumulation via activation of sGC and cGMP formation. These effects may be of
      particular importance in arterial tissue with reduced NO activity.

PMID- 11947905
TI  - Differential effects of gemfibrozil on migration, proliferation and proteoglycan
      production in human vascular smooth muscle cells.
AB  - The aim of this study was to determine, if gemfibrozil has anti-atherogenic
      actions on human vascular smooth muscle cells (SMCs) and whether these actions
      are affected by high glucose concentrations, which mimic the hyperglycemia of
      diabetes. Proliferation of SMCs treated with gemfibrozil was estimated by cell
      counting (Coulter Counter) and [3H]thymidine incorporation, migration in a scrape
      wound assay, proteoglycan (PG) biosynthesis and glycosaminoglycan (GAG) synthesis
      on xyloside by [35S]sulfate labeling and sizing by sodium dodecyl sulphide
      polyacrylamide gel electrophoresis (SDS-PAGE). Gemfibrozil (100 micromol/l) did
      not affect migration in low or high glucose media. Gemfibrozil caused
      concentration-dependent inhibition of proliferation in low glucose media (24%
      inhibition at 100 micromol/l, P<0.01) and inhibited the re-initiation of DNA
      synthesis by 33.3% (100 micromol/l, P<0.05) in low glucose and 31.4% (100
      micromol/l, P<0.001) in high glucose conditions. In low and high glucose media,
      gemfibrozil (100 micromol/l) reduced total PG production in the presence of TGF
      beta 1, which was associated with a decrease in the apparent size of PGs.
      Gemfibrozil and another PPAR-alpha ligand, WY-14643, significantly inhibited
      basal and TGF-beta1 stimulated GAG synthesis. We conclude that some SMCs
      properties associated with atherogenesis are favorably affected by gemfibrozil.
      Hence, direct vascular actions of gemfibrozil observed in this study may
      contribute to the reduction in cardiovascular disease observed in clinical
      studies with gemfibrozil.

PMID- 11947904
TI  - Inhibitory effect of a novel water-soluble vitamin E derivative on
      atherosclerosis in rabbits.
AB  - A novel vitamin E derivative that is freely soluble in water, 2-(alpha-D
      glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), was evaluated for
      ability to inhibit development of atherosclerosis in Watanabe heritable
      hyperlipidemic (WHHL) rabbits or cholesterol-loaded New Zealand White rabbits.
      Although TMG rapidly entered the circulation blood after oral administration, the
      blood TMG concentration remained low, while neither TMG nor its metabolites
      appeared in the low-density lipoprotein (LDL) fraction. TMG did not decrease
      serum total cholesterol and the various lipoprotein-associated cholesterol
      fractions (very LDL-, or high-density lipoprotein- (HDL) cholesterol). TMG
      reduced the serum concentration of thiobarbituric acid-reactive substances
      (TBARS; an index of lipid peroxidation) in cholesterol-loaded rabbits but not
      WHHL rabbits. Nonetheless, TMG inhibited aortic atherosclerosis as effectively as
      probucol in both models. Our results indicate that TMG opposes progression of
      atherosclerosis not only by preventing oxidation of LDL, but also by presently
      unknown mechanisms. Even an antioxidant with no uptake by LDL apparently can
      inhibit development of atherosclerosis despite a very low serum concentration.

PMID- 11947906
TI  - Effect of HDL, from Japanese white rabbit administered a new cholesteryl ester
      transfer protein inhibitor JTT-705, on cholesteryl ester accumulation induced by
      acetylated low density lipoprotein in J774 macrophage.
AB  - We have previously reported a potent and specific cholesteryl ester transfer
      protein (CETP) inhibitor JTT-705 was a potentially anti-atherogenic compound
      (Nature 406 (2000) 203). In the present study, we investigated in vitro how this
      compound affects properties of high density lipoprotein (HDL) in Japanese white
      (JW) rabbits in terms of reverse cholesterol transport in J774 macrophages.
      Plasma HDL-cholesterol (C) level was significantly higher in the rabbits
      administered JTT-705 than in control rabbits on days 3 and 7. Both HDL(2) and
      HDL(3)-C levels were also significantly higher in JTT-705-administered rabbits
      than in control rabbits. During this period, plasma CETP activity was kept lower
      in JTT-705-administered rabbits than in controls. To determine how this compound
      affects the property of HDL particles, we investigated the C efflux induced by
      HDL from JTT-705-administered and control rabbits in J774 macrophages.
      Cholesterol ester (CE) concentration in J774 macrophages was reduced in
      proportion with increasing concentration of the added HDL to the culture media
      for J774 macrophages in both groups, suggesting that the HDL from JTT-705
      administered rabbits was able to reduce CE concentration in J774 macrophages as
      efficiently as that from control rabbits. This result, together with the finding
      that the absolute HDL concentration increased in JW rabbits administered this
      CETP inhibitor, suggests that treatment with this new compound causes a
      beneficial effect on lipid metabolism in terms of anti-atherogenicity.

PMID- 11947907
TI  - Role of selenium in cytoprotection against cholesterol oxide-induced vascular
      damage in rats.
AB  - Wistar rats were fed Se-deficient (0.038 mg/kg diet) and adequate (0.326 mg/kg
      diet) diets for 13 weeks. The blood Se content, blood and vascular wall
      glutathione peroxidase (GPx) activity, serum high-density lipoprotein cholesterol
      (HDL-C) level and plasma prostacyclin (PGI(2)) concentration were decreased
      significantly, and the blood lipid peroxide (LPO) concentration, serum low
      density lipoprotein cholesterol (LDL-C), total cholesterol (TC) level and plasma
      thromboxane A(2) (TXA(2)), content were increased significantly in Se-deficient
      rats compared with Se-adequate group, respectively. Furthermore the Se-deficient
      and adequate rats were given 5 mg/kg of cholestane-3 beta, 5 alpha, 6 beta -triol
      (3-triol) or vehicle only. Twenty four hours after treatment, the plasma PGI(2)
      level was decreased in Se-adequate rats infused 3-triol (+3 triol), meanwhile,
      the level in Se- deficient +3-triol group was much lower than that in Se-adequate
      +3-triol group. Compared with Se-adequate group, plasma TXA(2) content in Se
      adequate +3-triol group had no significantly difference, but in Se- deficient
      rats infused 3-triol, plasma TXA(2) content was much higher than that in Se
      adequate +3-triol group. The plasma ET concentration in Se-deficient group
      decreased slightly, but the concentration in Se-adequate +3-triol group increased
      significantly with respect to Se-deficient group. Although plasma ET
      concentration in Se-deficient group +3-triol did not increase, it was
      significantly lower than that in Se-adequate +3-triol group. The luminal surfaces
      of aorta thoracica of experimental rats were examined by scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). Observed by SEM, the
      luminal surface of aorta of Se-deficient rats showed few crater-like defects due
      to the disruption of endothelial cell. Se-adequate +3-triol group showed some
      crater-like defects on the their aorta luminal surface, but the luminal surface
      of Se-deficient +3-triol group exhibited numerous crater-like defects and
      appeared sponge-like as well as platelets adhering followed by thrombus formation
      in focal area of extensive endothelial damage. TEM studies also showed that the
      endothelium of aorta of Se deficient +3-triol group had more frequent lesion
      where endothelial cell plasma were swelling with profuse intracellular edema and
      some vacuoles were seen in cytoplasm. In severely injured areas, endothelial
      integrity was completely destroyed and smooth muscle cells were proliferating and
      migrated to the endomembrane. Thus, we can conclude that Se or selenoproteins in
      the vascular wall plays an important role in cytoprotection against cholesterol
      oxide-induced vascular damage in rats.

PMID- 11947909
TI  - Hyperhomocyst(e)inemia and Chlamydia pneumoniae IgG seropositivity in patients
      with coronary artery disease.
AB  - Elevated levels of homocyst(e)ine and infection by Chlamydia pneumoniae have been
      hypothesized individually to play a role in coronary artery disease (CAD), but
      the mechanisms are unclear. Data on a possible association are not available. We
      investigated the correlation between IgG antibody titers against C. pneumoniae
      and fasting plasma homocyst(e)ine in 234 consecutive male patients with CAD.
      Chlamydial antibodies to a recombinant genus-specific lipopolysaccharide (LPS)
      were measured with ELISA. Total homocyst(e)ine (tHcy) concentrations were
      measured by high-performance liquid chromatography (HPLC). Thirty-seven subjects
      were classified hyperhomocyst(e)inemic (fasting homocyst(e)ine>14 micromol/l,
      group A), and 197 subjects were below cut-off (tHcy<14 micromol/l, group B).
      Prevalence of IgG seropositivity against C. pneumoniae was significantly higher
      in group A (68%) as compared to group B (39%, P=0.002). Antibody titers were also
      significantly higher in hyperhomocyst(e)inemic subjects than in cases with low
      homocyst(e)ine levels (P=0.002). Overall titers correlated significantly with
      tHcy levels (r(2)=0.222, P=0.001). Hyperhomocyst(e)inemia was associated with
      arterial hypertension (P=0.003), intake of lipid lowering drugs (P=0.022) and
      quite not with low folate concentration (P=0.052). No association was seen for
      IgG seropositivity or homocyst(e)ine and age, body mass index, smoking, diabetes,
      vitamin B(6) and B(12), cholesterol and triglycerides. These data indicate an
      association between elevated plasma homocyst(e)ine concentrations and chlamydial
      IgG antibody titers in patients with CAD.

PMID- 11947908
TI  - B-mode ultrasound-detected carotid artery lesions with and without acoustic
      shadowing and their association with markers of inflammation and endothelial
      activation: the atherosclerosis risk in communities study.
AB  - In a cross-sectional study of 8695 men and women free of clinical CVD, aged 45-64
      years at the 1987-1989 baseline Atherosclerosis Risk in Communities (ARIC) study
      exam, we examined the relationship between carotid artery lesions (CALs), with
      and without acoustic shadowing (AS) as an index of plaque mineralization, to
      systemic markers of inflammation and markers of endothelial function, including
      endothelial adhesion molecules. A three-level variable, based on the presence of
      extracranial CALs and AS, identified by B-mode ultrasound of six 1 cm arterial
      segments, defined the outcome. Among subjects without evidence of AS, after
      controlling for age, gender, ethnicity, study site, body mass index,
      hypertension, diabetes, and smoking status, CALs were associated with systemic
      markers of inflammation, including higher levels of fibrinogen [OR=1.24 (95% CI:
      1.09, 1.40)] and white blood cell count [OR=1.37 (95% CI: 1.21, 1.56)]. Among
      subjects with a CAL, after controlling for the above risk factors as well as mean
      far wall intima-media thickness, AS was associated with higher levels of von
      Willebrand factor [OR=1.38 (95% CI: 1.10, 1.74)], a marker of endothelial
      activation. Associations with endothelial adhesion molecules were inconsistent.
      Further studies aimed at elucidating the mechanisms of arterial mineralization
      are warranted.

PMID- 11947911
TI  - Carotid artery intima-media thickness in Finnish families with familial combined
      hyperlipidemia.
AB  - BACKGROUND: Familial combined hyperlipidemia (FCHL) is the most common hereditary
      lipid disorder that predisposes the patients to premature coronary heart disease.
      Members of FCHL families are categorised as affected or unaffected according to
      serum lipid levels. This study is aimed to evaluate whether there is a difference
      in carotid artery wall thickness between asymptomatic FCHL family members who are
      affected and those who are unaffected according to the currently used lipid
      criteria. METHODS AND RESULTS: Carotid artery ultrasonography with intima-media
      thickness (IMT) measurements was performed for 148 members of 39 Finnish FCHL
      families. Study subjects who had no history of coronary heart disease or stroke
      were divided into two groups according to their serum total cholesterol and/or
      triglyceride levels. The average carotid IMT of the affected subjects (0.75+/
      0.15 mm) was not significantly different from that of their unaffected relatives
      (0.73+/-0.13 mm), P=0.90. In multivariate analysis, age, gender, and pulse
      pressure, but no lipid variables, contributed significantly to the variation of
      carotid IMT. CONCLUSIONS: The IMT findings in FCHL family members indicate that
      the current lipid criteria alone are of limited value in predicting long-term
      risk of cardiovascular disease in asymptomatic members of FCHL families.

PMID- 11947910
TI  - Effects of atorvastatin on postprandial plasma lipoproteins in postinfarction
      patients with combined hyperlipidaemia.
AB  - Enhanced and prolonged postprandial lipaemia is implicated in coronary and
      carotid artery disease. This study assessed the effects of atorvastatin, a 3
      hydroxy-3-methylglutaryl-CoA reductase inhibitor, on postprandial plasma
      concentrations of triglyceride-rich lipoproteins (TRLs). Sixteen middle-aged men
      with combined hyperlipidaemia (baseline low density lipoprotein (LDL) cholesterol
      and plasma triglyceride concentrations (median (interquartile range) of 4.54
      (4.17-5.26)) and 2.66 (2.04-3.20) mmol/l, respectively) and previous myocardial
      infarction were randomised to atorvastatin 40 mg or placebo once daily for 8
      weeks in a double-blind, cross-over design. The apolipoprotein (apo) B-48 and B
      100 contents were determined in subfractions of TRLs as a measure of chylomicron
      remnant and very low density lipoprotein (VLDL) particle concentrations
      (expressed as mg apo B-48 or apo B-100 per litre of plasma), in the fasting state
      and after intake of a mixed meal. Atorvastatin treatment reduced significantly
      the fasting plasma concentrations of VLDL cholesterol, LDL cholesterol and VLDL
      triglycerides (median% change) by 29, 44 and 27%, respectively, and increased
      high density lipoprotein (HDL) cholesterol by 19%, compared with baseline. The
      postprandial plasma concentrations of large (Svedberg flotation rate (Sf) 60-400)
      and small (Sf 20-60) VLDLs and chylomicron remnants were almost halved compared
      with baseline (mean 0-6 h plasma concentrations were reduced by 48% for Sf 60-400
      apo B-100, by 46% for Sf 60-400 apo B-48, by 46% for Sf 20-60 apo B-100 and by
      27% for Sf 20-60 apo B-48), and the postprandial triglyceridaemia was reduced by
      23% during active treatment. In conclusion, atorvastatin 40 mg once daily causes
      profound reductions of postprandial plasma concentrations of all TRLs in combined
      hyperlipidaemic patients with premature coronary artery disease.

PMID- 11947913
TI  - Highly effective reduction of C-reactive protein in patients with coronary heart
      disease by extracorporeal low density lipoprotein apheresis.
AB  - An association between C-reactive protein (CRP) and coronary heart disease (CHD)
      has been shown. CRP is present in atherosclerotic lesions, and there is
      increasing evidence that it may contribute to inflammation. Reduction of CRP
      concentrations otherwise considered normal may thus be of therapeutic value.
      Heparin-induced extracorporeal low density lipoprotein precipitation (HELP) is an
      established apheresis procedure to treat CHD patients with hypercholesterolemia.
      CRP concentrations were determined pre- and post-apheresis in 13
      hypercholesterolemic CHD patients, during a total of 31 treatment procedures as
      well as in the interval between two treatments in six-patients using a high
      sensitivity CRP assay. In addition, the effect of the HELP precipitation buffer
      on serum CRP concentrations was investigated in vitro. HELP treatment reduced CRP
      concentrations on average by 65%. The presence of CRP in the LDL precipitate of a
      patient was also confirmed by Western-blot analysis. In vitro experiments with
      serum samples revealed that CRP was partly co-precipitated with LDL. Greater
      fluctuation was observed in the post-apheresis concentrations of CRP compared
      with LDL. These results show that CRP can be very effectively lowered in CHD
      patients through the HELP system. This may further explain the stabilization and
      reduction of atherosclerotic plaques in hypercholesterolemic patients previously
      demonstrated with this treatment procedure.

PMID- 11947912
TI  - Reduced expression of endothelial cell markers after 1 year treatment with
      simvastatin and atorvastatin in patients with coronary heart disease.
AB  - The study was aimed at investigating the effects, after treatment for 1 year, of
      two different statins on the levels of circulating biochemical markers of
      endothelial function in patients with established coronary heart disease, with
      the hypothesis that statins might reduce these levels. Twenty-eight patients were
      randomized to treatment with atorvastatin and 30 to simvastatin for 1 year. The
      starting dose in both groups was 20 mg/day. Soluble forms of P-selectin, E
      selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion
      molecule-1 (VCAM-1) were determined to assess inflammatory activity of the
      endothelium, and tissue plasminogen activator antigen (tPAag), von Willebrand
      factor and thrombomodulin for evaluation of the haemostatic function. In the
      total study population there were significantly reduced levels after 1 year
      treatment in ICAM-1 (P<0.001), E-selectin (P=0.022) and P-selectin (P<0.001),
      whereas a significant increase was observed in VCAM-1 (P=0.003). Almost the same
      pattern was seen within both groups although the increase in VCAM-1 was only seen
      in the simvastatin group (P=0.017). An overall reduction in tPAag was further
      observed (P=0.048). The reduction in proinflammatory and to some extent
      haemostatic markers of endothelial function after 1 year treatment with either
      simvastatin or atorvastatin may be indicative of a less activated state of the
      endothelium which possibly may contribute to modulation of the progression of
      atherosclerosis.

PMID- 11947914
TI  - Homocysteine and methylenetetrahydrofolate reductase genotype: association with
      risk of coronary heart disease and relation to inflammatory, hemostatic, and
      lipid parameters.
AB  - AIM: It has been suggested that homocysteine (tHcy) levels and
      methylenetetrahydrofolate reductase (MTHFR) genotype are primary risk factors for
      coronary heart disease (CHD). We performed a case-control study to investigate
      whether tHcy levels and MTHFR genotype (677 C-->T mutation and 1298 A-->C
      mutation) are associated with CHD under special consideration of the possibility
      for confounding. METHODS: German speaking patients aged 40-68 years who underwent
      coronary angiography at the University of Ulm between April 1996 and November
      1997 and who had at least one coronary stenosis greater than 50% were included in
      the study. Controls were sampled from voluntary blood donors and were matched for
      sex and age. tHcy levels were measured by high performance liquid chromatography
      and MTHFR genotype by means of polymerase chain reaction. In addition, C-reactive
      protein, fibrinogen, plasma viscosity, leukocytes, HDL-cholesterol and Lp(a) were
      determined. RESULTS: Overall, 312 patients and 479 controls were enrolled in the
      study (response in patients 78%, in controls 84%). Mean tHcy value was 9.43
      micromol/l in CHD patients and 8.91 micromol/l in controls (P=0.145). Prevalence
      of 677TT-polymorphism was 9.9% in patients and 10.4% in controls (P=0.295).
      Prevalence of 1298CC-polymorphism was 9.7% in patients and 13.8% in controls
      (P=0.346). There was a clear association of tHcy-values, but not of 677TT- or
      1298CC-genotype with conventional CHD risk factors. After adjustment for these
      risk factors no increased risk for CHD could be associated with increased tHcy
      values, with 677TT or 1298CC-genotype, or with their combination. Also no
      statistically significant relationships of these parameters to inflammatory,
      rheologic or hemostatic parameters or lipids were detectable. CONCLUSION: These
      results do not confirm an independent relationship of tHcy values and MTHFR
      genotype with risk of CHD in the population studied.

PMID- 11947915
TI  - A comparison of pravastatin and gemfibrozil in the treatment of
      dyslipoproteinemia in patients with non-insulin-dependent diabetes mellitus.
AB  - The effects of pravastatin (pravachol) compared with gemfibrozil on cholesterol
      rich and trigylceride-rich lipoproteins were evaluated in this multi-centered
      trial. Following an 8-12 week prerandomization phase, 136 patients with NIDDM and
      hypercholesterolemia were randomized to receive either pravastatin 40 mg or
      gemfibrozil 1200 mg daily for 16 weeks. The reduction of total cholesterol (TC),
      betaquant LDL and LDL cholesterol (LDL-C) was significantly greater in patients
      treated with pravastatin than with gemfibrozil. However, gemofibrozil treatment
      resulted in a significantly greater reduction of triglyceride (TG) levels than
      did treatment with pravastatin. Pravastatin reduced the concentration of apoB (
      19.3%, P<0.001) and cholesterol-rich Lp-B (Lp-B+Lp-B; E) particles (-19%,
      P<0.001) to a significantly greater extent (P<-0.001) than gemfibrozil (-4.1 and 
      1%, respectively). Both gemfibrozil and pravastatin reduced the concentrations of
      trigylceride-rich Lp-Bc (-12.2 and -13.3%, respectively) and Lp-A-II;B;C;D;E (-19
      and -12.7%, respectively) particles and their characteristic apoC-III constituent
      (-10.0 and -7.0%, respectively). In contrast, gemfibozil has a greater lowering
      effect compared with pravastatin on TG levels (-29.6 vs. -6.3%, respectively).
      Both pravastatin and gemfibrozil significantly increased the levels of apoA-I
      and, with both drugs, the elevated concentrations of apoA-I were due to
      significantly increased levels of Lp-A-I;A-II particles. By decreasing both
      cholesterol-rich Lp-B and triglyceride-rich Lp-Bc particles and increasing HDL-C
      and Lp-A-I;A-II particles in addition to proven efficacy in decreasing coronary
      events in NIDDM patients, pravastatin appears to be an appropriate choice for
      monotherapy in a broad range of diabetic patients with Type IIA and Type IIB
      hyperlipoproteinemias. These results also showed that direct measurement of
      lipoprotein family of particles provides important information not only about the
      composition but also the type and number of apoA- and apoB-containing lipoprotein
      particles.

PMID- 11947916
TI  - Sudden death and myocardial infarction in first degree relatives as predictors of
      primary cardiac arrest.
AB  - The hypothesis that family history (FH) of myocardial infarction (MI) and FH of
      sudden death (SD) are both independent risk factors for primary cardiac arrest
      (PCA) was examined in a case-control study. PCA cases were attended by paramedics
      (1988-1994) and community-based age and sex matched controls were identified.
      Subjects (25-74 years) were free of prior clinically-recognized heart disease and
      major co-morbidity. Interviewers obtained a detailed history of MI and SD in
      first-degree relatives from spouses of 235 cases and 374 control subjects. A
      parental history of early-onset SD (age <65) was associated with an increased
      risk of PCA (odds ratio (OR)=2.69, 95% CI=1.35-5.36), after adjustment for
      parental history of MI and other risk factors. A parental history of late-onset
      SD was not associated with PCA risk (OR=0.94, 95% CI=0.55-1.62). Additionally,
      parental history of SD was related to early-onset PCA (OR=1.89, 95% CI=1.08-3.30)
      but not to late-onset PCA (OR=0.89, 95% CI=0.49-1.61). In contrast, parental MI
      (early/late) was related to PCA (early/late), after adjustment for other risk
      factors and parental history of SD. Similar results were observed in first-degree
      relatives. Findings suggest a potential role of familial factors related to both
      MI and SD in PCA. Stronger findings for a familial patterning of PCA were noted
      for early onset disease in cases and their relatives.

PMID- 11947917
TI  - Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of
      CRP, and the risk of future arterial thrombosis.
AB  - While increased concentrations of C-reactive protein (CRP) are associated with
      increased vascular risk, little information is available describing genetic
      determinants of this effect. In a large prospective cohort of apparently healthy
      men, we found plasma CRP concentrations to be significantly reduced among
      carriers of a 1059G/C polymorphism in the human CRP gene (GC or CC) as compared
      with non-carriers (GG). However, the polymorphism examined was not significantly
      associated with risk of arterial thrombosis despite the fact that CRP
      concentrations are a potent independent predictor of future vascular events in
      this cohort. These data suggest that genetic and environmental determinants each
      importantly contribute to the vascular risk associated with inflammation.

PMID- 11947918
TI  - Increased level of advanced oxidation protein products in patients with coronary
      artery disease.
AB  - Witko-Sarsat et al. previously reported that advanced oxidation protein products
      (AOPP), which were determined by measurements of optical density (OD) at 340 nm
      under acidic conditions, were present at high levels in the plasma of uremic
      patients. We measured AOPP in the plasma of 392 patients who underwent coronary
      angiography because of suspected coronary artery disease (CAD) and examined the
      association between plasma AOPP levels and CAD. We also collected plasma from
      hemodialysis patients and healthy volunteers for AOPP assay. Plasma fractionation
      by size-exclusion chromatography was performed to determine the weights of the
      molecules involved in the AOPP activity. The elution patterns obtained after
      plasma fractionation by size-exclusion chromatography were the similar in both
      CAD and hemodialysis patients, but differed from those of the healthy volunteers,
      whose AOPP levels were low. We also found that, the severity score of CAD
      obtained by the Gensini scoring system had good correlation with AOPP quartiles.
      Multivariable regression models revealed that the plasma AOPP level was
      significantly related to CAD status. This is the first report of an association
      between AOPP and CAD. AOPP was an independent risk factor for CAD. Oxidative
      stress is speculated to be associated with the pathogenesis of CAD.

PMID- 11947919
TI  - Glutathione S-transferases and related proteins from pathogenic human parasites
      behave as immunomodulatory factors.
AB  - There is a rapidly expanding interest into the glutathione S-transferases (GSTs)
      and the structurally related molecules. Many of the latter have been identified
      as members of conserved protein families sharing structural and some times
      functional properties being particularly involved in heat-shock response, drug
      resistance and carcinogenesis. Also, evidence is emerging that members of the GST
      super family from some pathogens could exert immunomodulatory functions toward
      the cell of the immune system, involving separate profiles of cytokine gene
      transcription and different patterns of cell growth, illustrating therefore the
      'one gene-dual function' phenomenon. The implication of these biological
      properties for pathogenesis is discussed.

PMID- 11947920
TI  - Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation
      of NF-kappaB, ERK and p38 MAPK signal pathways.
AB  - Toll-like receptors (TLR) are critical in the activation of macrophages by
      bacterial products. It has been shown that TLR2 and TLR4 mediate
      lipopolysaccharide (LPS) and lipoproteins signal transduction, respectively.
      Regulation of TLR2 and TLR4 expression by LPS was considered to be one of the
      mechanisms to control the overall responses of immune cells to bacteria. However,
      little is known about whether the other members of TLR family are regulated by
      LPS. Recently, TLR9 was demonstrated to be essential for CpG DNA signaling. Given
      the effective immune modulation by CpG DNA, regulation of TLR9 expression might
      play important role in controlling the overall responses of immune cells to
      bacteria. In this study, regulation of TLR9 gene expression in mouse macrophage
      cell line RAW264.7 by LPS was investigated. Semiquantitative RT-PCR was performed
      to determine gene expression of TLR9. Following LPS stimulation, TLR9 gene
      expression was upregulated within 1 h and reached peak level at about 3 h. LPS
      stimulation activated NF-kappaB, ERK and p38 MAPK signal pathways. Pretreatment
      of macrophages with inhibitors of NF-kappaB, ERK and p38 MAPK signal pathways
      inhibited LPS-induced upregulation of TLR9 mRNA expression. Our results
      demonstrated that LPS stimulation could upregulate gene expression of TLR9 via NF
      kappaB, ERK, and p38 MAPK signal pathways in macrophages, indicating that
      macrophages with increased TLR9 expression induced by LPS might respond to
      invading bacteria more effectively.

PMID- 11947921
TI  - Identification of candidate genes for Sjogren's syndrome using MRL/lpr mouse
      model of Sjogren's syndrome and cDNA microarray analysis.
AB  - Sjogren's syndrome is a chronic autoimmune disease characterized by focal
      lymphocytic infiltration of lacrimal and salivary glands, but the precise
      mechanism of this syndrome is poorly understood. To clarify the mechanism of
      onset and progression of Sjogren's syndrome, it is necessary to identify
      Sjogren's syndrome-related genes. For this purpose, we used MLR/MpJ-lpr/lpr
      (MRL/lpr) mouse as a model of human secondary Sjogren's syndrome and analyzed
      specific mRNA expression pattern in MRL/lpr mouse salivary glands by in-house
      cDNA microarray. Among arrayed 2304 genes, 13 genes were isolated as highly
      expressed genes in MRL/lpr mouse salivary gland in comparison with MRL/MpJ-+/+
      (MRL/+) mouse tissue. Subsequently, we performed RT-PCR analysis and confirmed
      the high expression level of nine genes; caspase3, Ly-6C.2, vimentin, Mel-14
      antigen, cathepsin B, mpt1, Laptm5, Gnai2 and UCP2. Five of the nine genes have
      already been identified in patients with Sjogren's syndrome or mice models of the
      syndrome, but the remaining four genes; mpt1, Laptm5, Gnai2, and UCP2 have not
      been reported previously as Sjogren's syndrome-related genes. Although, further
      experiments are necessary to examine the relationship between these four genes
      and Sjogren's syndrome, our system of mouse model of Sjogren's syndrome combined
      with in-house cDNA microarray is suitable for the isolation of Sjogren's syndrome
      related genes.

PMID- 11947922
TI  - Tumor necrosis factor microsatellite alleles in patients with rheumatoid
      arthritis in Taiwan.
AB  - OBJECTIVE: To investigate the association of tumor necrosis factor (TNF)
      microsatellite alleles with the pathogenesis of rheumatoid arthritis (RA) in
      Taiwan. METHODS: The TNF a, b, c, d, and e microsatellites were determined in 112
      patients with RA and 99 healthy controls by using polymerase chain reaction (PCR)
      and electrophoresis with sequencing gel. All of these patients and controls had
      known HLA-DR genotypes and TNF-308 polymorphisms. RESULTS: The phenotypic
      frequency of TNFa9 was significantly higher in DR4(-) RA patients than in DR4(-)
      controls. However, the phenotypic frequency of TNFb6 was significantly higher in
      RA patients than in controls in the presence of HLA-DR4. The phenotypic frequency
      of TNFa3-e1 was significantly lower in DR4(+) RA patients than in DR4(+)
      controls, while a negative linkage disequilibrium was noted between TNFa3-e1 and
      HLA-DR4. TNF microsatellite alleles were not related to the prevalences of bone
      erosion, rheumatoid nodule, sicca syndrome, pulmonary fibrosis, and
      seropositivity of rheumatoid factor (RF) in patients with RA. CONCLUSION: The
      associations of TNF microsatellites with the susceptibility to RA in Taiwan are
      not completely independent of the HLA-DR associations. The association of TNFb6
      with the susceptibility to RA depends on the presence of HLA-DR4, and the
      correlation of TNFa9 to RA depends on the absence of HLA-DR4. The negative
      association of TNFa3-e1 with RA may be secondary to the negative linkage
      disequilibrium between TNFa3-e1 and HLA-DR4. Moreover, TNFb6 and HLA-DR4 have a
      synergistic effect on the susceptibility to RA. TNFa3-e1 and TNF-308A have a
      synergistic effect on preventing from RA. The TNF microsatellite alleles are not
      related to the clinical manifestations and severity of RA patients in Taiwan.

PMID- 11947923
TI  - Natural killer activity in the experimental privational rickets.
AB  - To study the 'in vivo' importance of vitamin D on the natural killer (NK)
      activity, rats were submitted to privational rickets induced by a diet deficient
      in vitamin D and phosphorus (D-P-). Thirty days after the beginning of treatment
      the animals showed low body weight, changes in the bone development, and
      decreased levels of 25-hydroxyvitamin D(3) (25-OH D(3)). NK activity, evaluated
      using a cytotoxicity assay against 51Cr-labeled Yac.1 target cells, was not
      modified by the rickets-inducing treatment during the first 30 days. Following a
      long-term treatment (60 days) the rachitic rats (D-P-) exhibited higher NK
      activity than control animals (D+P+) (P<0.05). On the other hand, D-P+ animals
      showed higher cytotoxic activity than D-P- and D+P+ groups. Feed replacement to
      the rachitic rats by a complete diet (D-P-/D+P+) led to a partial recuperation of
      growth, bone development, and 25-OH D(3) serum levels. The NK activity was also
      influenced by vitamin D intake, decreasing after treatment.

PMID- 11947925
TI  - Reference values of lymphocyte subsets in the normal healthy adult Kuwaiti Arab
      population.
AB  - Fluorescent monoclonal antibody labelling followed by a lysed whole blood method
      and flow cytometry was used to determine the lymphocyte subpopulations in 127 (64
      males and 63 females) normal healthy individuals in the adult (age 18-59 years)
      Kuwaiti population. Relative percentages and absolute values of CD2+, CD3+,
      CD19+, CD4+, CD8+, HLADR+, CD56+, CD45RO+, and CD45RA+ cells were determined. The
      reference ranges were CD2+, 73-92% (0.95-2.99 x 10(9) per l), CD3+, 64-85% (0.83
      2.71 x 10(9) per l), CD19+, 6-22% (0.05-0.61 x 10(9) per l), CD4+, 34-54% (0.45
      1.65 x 10(9) per l), CD8+, 20-42% (0.29-1.17 x 10(9) per l), HLADR+, 4-23% (0.02
      0.62 x 10(9) per l), CD56+, 4-22% (0.06-0.58 x 10(9) per l), CD45RO+, 16-53%
      (0.26-1.42 x 10(9) per l) and CD45RA+, 35-72% (0.34-2.05 x 10(9) per l). The mean
      CD4/CD8 ratio was 1.50+/-0.35. CD3+ cells were positively correlated to both CD4+
      and CD8+ cells (P<0.001), and CD4+ cells showed a significant positive
      correlation with CD8+ cells (P<0.001).

PMID- 11947924
TI  - Catalytic diversity of polyclonal RNA-hydrolyzing IgG antibodies from the sera of
      patients with systemic lupus erythematosus.
AB  - Various catalytic antibodies or abzymes have been detected in the sera of
      patients with several autoimmune pathologies, and recently we have shown that
      RNase activity is associated with IgGs and IgMs from the sera of patients with
      systemic lupus erythematosus (SLE) but not with those from the sera of normal
      humans. Here we present for the first time convincing evidence showing that
      highly purified SLE IgG, its F(ab) fragments and separated L-chains catalyze RNA
      hydrolysis. These IgGs hydrolyze RNA about one to three orders of magnitude
      faster than DNA. The enzymatic properties of the RNase activity of these
      polyclonal IgGs distinguish them from other known human RNases. Their specific
      activity in hydrolysis of ribooligoadenylates is 2-100-fold higher than that of
      RNase A and human serum RNases, and they are markedly more thermolabile. In
      addition, their specific activities with different oligonucleotide substrates,
      optimal pHs, apparent K(m) values for substrates, and substrate specificities
      varied very much for different patients. These findings show that a pool of
      polyclonal RNA-hydrolyzing IgG, which may be relatively small or extremely large,
      is generated by the immune system of SLE patients.

PMID- 11947926
TI  - Reduced levels of gamma-interferon secretion in response to chlamydial 60 kDa
      heat shock protein amongst women with pelvic inflammatory disease and a history
      of repeated Chlamydia trachomatis infections.
AB  - Peripheral lymphocytes in uninfected fertile controls, women with various
      histories of Chlamydia trachomatis infection, pelvic inflammatory disease (PID)
      and infertility not due to C. trachomatis infection (endometriosis) were cultured
      overnight with PHA mitogen and the 60 kDa chlamydial heat shock protein. Plasma
      samples were then assayed for levels of gamma-interferon and IL-10 using a
      commercial ELISA system. Women with PID and those with a history of multiple C.
      trachomatis infections showed reduced gamma-interferon production in response to
      cHSP60, not seen in women infected only once and those with infertility due to
      other causes (endometriosis). Secretion of IL-10 in response to cHSP60 did not
      vary significantly across the various patient groups, though all patients showed
      elevated levels of total IL-10 compared with uninfected controls.

PMID- 11947927
TI  - Seeding of dendritic epidermal T cells in the neonatal skin is reduced in 129
      strain of mice.
AB  - Precursors for Thy-1(+) dendritic epidermal T cells (DETC) develop as Vgamma3(+)
      T cells in the fetal thymus and become distributed in the adult skin. DETC are
      variably distributed from site to site and from strain to strain. To elucidate
      the basis of strain variation, we first compared the density of DETC in the ear
      epidermis among different mouse strains. In the ear epidermis, we detected the
      highest level of DETC in C57BL/6 mice, intermediate levels in C3H and CBA/J mice,
      and the lowest levels in other strains including BALB/c and 129 mice. Although
      BALB/c and 129+Ter/Sv mice showed higher levels of DETC in the abdomen than in
      the ear, the levels were significantly lower than C57BL/6 mice. Furthermore, in
      neonatal abdominal epidermis we detected considerably lower numbers of DETC in
      BALB/c and 129+Ter/Sv mice than in C57BL/6 mice. In contrast, Vgamma3(+) DETC
      precursors in the fetal thymus are rather increased in 129+Ter/Sv mice. These
      results suggest that fewer DETC precursors are seeded in the neonatal skin of
      BALB/c and 129+Ter/Sv mice and that their expansion in the skin during neonatal
      to adult stages does not reach the levels in C57BL/6 mice.

PMID- 11947928
TI  - Zonula occludens toxin (Zot) interferes with the induction of nasal tolerance to
      gliadin.
AB  - Both nasal and oral administration of soluble protein antigens (Ags) induce
      tolerance, a phenomenon that has hampered mucosal vaccine design. To produce
      active immunity the use of adjuvants co-administered with soluble Ags is
      required. Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT)
      were found to be powerful mucosal adjuvants, but they are not suitable for
      clinical use because of their associated toxicity. Therefore, there is the need
      to develop alternative strategies to deliver Ag in order to induce
      immunoprotection. Among these innovative tools, a new toxin, Zonula occludens
      toxin (Zot), produced by phages in toxigenic strains of Vibrio cholerae, has been
      recently exploited for its adjuvant activity at the mucosal level. The present
      study was undertaken to further highlight the adjuvant properties of Zot. The
      ability of Zot to induce a mucosal response to gliadin was demonstrated per serum
      antibody production. In our established model of systemic tolerance to gliadin,
      induced by its nasal administration, we found a reduced production of interferon
      gamma (IFN-gamma) and interleukin-2 (IL-2) upon administration of gliadin alone.
      This immune suppression was reverted in mice receiving gliadin together with Zot.
      As previously shown, the down-regulation of Th1-like cytokines was found to be
      associated to a suppression of the T-cell proliferation, while such a suppression
      was completely reverted by Zot co-administration. In conclusion, these data
      confirm Zot as a good mucosal adjuvant, considering its ability to interfere with
      the suppression of specific cell mediated immunity, probably as a result of the
      increased dose and/or altered processing of Ag at mucosal level.

PMID- 11947929
TI  - Lymphocyte binding to MAdCAM-1 via alpha4beta7 integrin activates a signal
      transduction pathway involving tyrosine phosphorylation of paxillin and p105(Cas
      L).
AB  - Alpha4beta7 integrin mediates lymphocyte trafficking to mucosal lymphoid organs
      by interacting with the mucosal vascular addressin MAdCAM-1. While the structural
      basis for the alpha4beta7 integrin-MAdCAM-1 interaction has been well
      characterized, less is known about the signal transduction pathways that regulate
      the alpha4beta7 integrin-mediated lymphocyte interaction with MAdCAM-1-expressing
      endothelial cells. Here we demonstrate that ligation of alpha4beta7 integrin with
      MAdCAM-1 induces a prominent tyrosine phosphorylation of paxillin and a 105-kDa
      protein (p105) that is reactive with an anti-p130(Cas) antibody, in the mouse T
      cell line TK-1. Cloning and expression of a full-length cDNA encoding the mouse
      p105(Cas-L) revealed that the p105 molecule is a mouse ortholog of p105(Cas-L).
      We also demonstrated that crosslinking of alpha4beta7 integrin with MAdCAM-1
      induces the rapid tyrosine phosphorylation of paxillin and p105(Cas-L) in normal
      lymphocytes and that PMA stimulation enhances the tyrosine phosphorylation of
      p105(Cas-L) but not of paxillin. These results suggest that intracellular signals
      initiated by alpha4beta7 integrin involve the tyrosine phosphorylation of
      paxillin and p105(Cas-L), which are differentially regulated, at least in part,
      by mechanisms that are PMA-sensitive or -insensitive.

PMID- 11947930
TI  - Intramuscular co-injection of naked DNA encoding HBV core antigen and Flt3 ligand
      suppresses anti-HBc antibody response.
AB  - Flt3 ligand, a recently described growth factor affecting early hematopoietic
      progenitor cells, can also support the expansion of dendritic cells secreting IL
      12. Its potential use in a clinical setting has been suggested. Here, we studied
      the effect of in situ delivery of Flt3 ligand plasmid (FL) on the antibody
      response induced by DNA vaccine encoding wild-type hepatitis B virus core antigen
      (HBc/w). Intramuscular injection of FL increased the expression of DEC205 and the
      size of splenocytes, and immunization with HBc/w or HBc/w-transfected EL-4 cells
      induced strong anti-HBc antibody responses in mice. However, intramuscular
      injection of FL with HBc/w significantly suppressed HBc/w-induced antibody
      response in a dose-dependent manner. Suppression of immune response by FL
      injection was the most prominent when FL and HBc/w were co-injected at the same
      time and the same site. These results suggest that FL may inhibit humoral
      response induced by DNA-type vaccination, and DC locally expanded by FL may not
      have proper functions for induction of humoral response.

PMID- 11947931
TI  - The anti-tumor activity of bacillus Calmette-Guerin in bladder cancer is
      associated with an increase in the circulating level of interleukin-2.
AB  - Bacillus Calmette-Guerin (BCG) is currently employed in the treatment of
      superficial bladder cancer but, despite its recognized effectiveness in
      preventing recurrences and progression, the immune mechanisms behind its
      antitumor activity remain to be delineated. In this study we provide evidence
      that a prolonged increase in the plasma levels of IL-2, but not IL-1beta, IL-4,
      IL-10, IL-2R or TNF-alpha occured in patients affected by bladder cancer
      following effective BCG treatment. Conversely, a drop in circulating IL-2 was
      consistently associated with tumor relapse. The level of IL-2 was elevated even
      further 15 days after the last BCG administration in patients who did not
      experience tumor recurrence, suggesting a prolonged T cell-mediated response
      against antigens other than BCG. Our results indicate that a specific type 1
      immune response plays a major role in the anti-cancer activity of BCG. In
      addition, monitoring IL-2 plasma levels may offer a useful tool for predicting
      tumor recurrences.

PMID- 11947932
TI  - Genetic influence on phenotypic differentiation in adult hippocampal
      neurogenesis.
AB  - Regulation of adult hippocampal neurogenesis has different regulatory levels,
      including cell proliferation, survival and differentiation. Cell proliferation
      and survival are differentially influenced by inheritable traits and the genetic
      background determines which regulatory levels of adult hippocampal neurogenesis
      are preferentially involved in a neurogenic response to environmental stimuli. We
      here compared baseline adult neurogenesis in wild-derived strain Mus spretus and
      three inbred laboratory strains: A/J, C3H/HeJ and DBA/2J. Proliferation of was
      similar in the four strains, with the extremes being A/J, which had about 2100+/
      570 (mean+/-S.D.) labeled newborn cells per dentate gyrus (after 6 days of
      bromodeoxyuridine injections), and DBA/2J, which had approximately 1400+/-260.
      C3H/HeJ had approximately 1500+/-600 and M. spretus had 1550+/-270. Survival of
      new cells after 4 weeks was 19% in A/J and DBA/2J, and 21% in M. spretus, but 37%
      in C3H/HeJ. Survival in C3H/HeJ was significantly different from DBA/2.
      Phenotypic analysis revealed that DBA/2J produced significantly fewer new neurons
      than A/J and C3H/HeJ (47% vs. 63% and 67%) but significantly more new astrocytes
      than A/J and C3H/HeJ (28% vs. 9% and 11%). In absolute terms there were 370+/-120
      new neurons in C3H/HeJ, 250+/-60 in A/J, 130+/-50 in DBA/2J, and 190+/-130 in M.
      spretus. Our results indicate that regulation of adult hippocampal neurogenesis
      affects the level of phenotypic differentiation. At the present time it cannot be
      determined whether this regulation occurs by influencing cell fate decisions or
      by promoting selective survival.

PMID- 11947933
TI  - Is it all DNA repair? Methodological considerations for detecting neurogenesis in
      the adult brain.
AB  - Since the early 1960s, in vivo observations have shown the generation of new
      neurons from dividing precursor cells. Nevertheless, these experiments suffered
      from skepticism, suggesting that the prevailing labeling method, which
      incorporates tagged thymidine analogs, such as [3H]-thymidine or
      bromodeoxyuridine (BrdU), may not be detecting a proliferative event, but could
      rather mark DNA repair in postmitotic neurons. Even today many scientists outside
      the field are still skeptical, because the question of specificity for thymidine
      labeling has not been sufficiently answered. This current paper aims at
      evaluating the arguments that are used by proponents and skeptics of this method
      by (i) presenting histological evidence of specificity of BrdU labeling for
      neural stem cell/progenitor activity in the adult brain; (ii) validating and
      comparing BrdU labeling with other histological methods; and (iii) combining BrdU
      and labeling methods for apoptosis to argue against DNA repair being a major
      contribution of BrdU-positive cells.

PMID- 11947934
TI  - Neurogenesis following brain ischemia.
AB  - Following 5 or 10 min of global ischemia in the adult gerbil there is a tenfold
      increase in the birth of new cells in the subgranular zone of dentate gyrus of
      the hippocampus as assessed using BrdU incorporation. This begins at 7 days,
      peaks at 11 days, and decreases thereafter. Over the next month approximately 25%
      of the newborn cells disappear. Of the remaining cells, 60% migrate into the
      granule cell layer where two-thirds become NeuN, calbindin and MAP-2
      immunostained neurons. The remaining 40% of the cells migrate into the dentate
      hilus where 25% of these become GFAP labeled astrocytes. It is proposed that
      ischemia-induced neurogenesis contributes to the recovery of function, and
      specifically may serve to improve anterograde and retrograde recent memory
      function that is lost following global ischemia in animals and man.

PMID- 11947935
TI  - A comparative study of neurogenesis in the retinal ciliary marginal zone of
      homeothermic vertebrates.
AB  - The retina of many fish and amphibians grows throughout life, roughly matching
      the overall growth of the animal. The new retinal cells are continually added at
      the anterior margin of the retina, in a circumferential zone of cells, known as
      the ciliary marginal zone, or CMZ. Recently, Fischer and Reh [Dev. Biol. 220
      (2000) 197] have found that new neurons are added to the retina of the chicken
      via proliferation and subsequent differentiation of neurons and glia at the
      retinal margin in a zone highly reminiscent of the CMZ of lower vertebrates. In
      addition, other groups have reported that putative retinal stem cells could be
      isolated from the ciliary margin of the adult mouse. In light of these findings,
      we have re-investigated the eyes of three additional species to determine whether
      other homeothermic vertebrates also possess CMZ cells and whether we could detect
      evidence for addition of neurons at the retinal margin in mature animals. We
      examined one additional avian species, the quail, one marsupial, the opposum, and
      one mammal, the mouse. We find that the CMZ cells have been gradually diminished
      during vertebrate evolution. The quail has a reduced CMZ as compared to the
      chicken, while the opposum has only a few cells likely related to the CMZ and we
      failed to find evidence of CMZ cells at the margin of the mouse retina.

PMID- 11947936
TI  - Regional specification of rodent and human neurospheres.
AB  - Neural precursor cells were isolated from various regions of the developing rat
      and human brain and grown in culture as aggregates termed neurospheres. We asked
      whether cells within human and rodent neurospheres are identical, or whether they
      have species specific characteristics or differences based on their region of
      origin. Under our culture conditions, rodent neurospheres isolated from the
      cortex (ctxNS) and striatum (strNS) grew faster than those from the mesencephalon
      (mesNS), but stopped growing after only eight to ten population doublings. In
      contrast, human neurospheres under identical culture conditions, continued to
      grow for over 40 population doublings. Following migration and differentiation of
      both rodent and human cultures, ctxNS and strNS generated high numbers of small
      neurons whereas mesNS generated small numbers of large neurons with many long
      fibres. Only very rare neurons from mesNS expressed dopaminergic markers, and
      thus may require further signals to fully mature. While the rat neurospheres
      generated high numbers of oligodendrocytes, very few were found to develop from
      human neurospheres from any region after a few weeks of passaging. FACS analysis
      revealed a unique population of smaller cells within human strNS and ctxNS, which
      appeared to be neuronal progenitors. However, large cells within neurospheres
      were capable of generating these small neuronal progenitors following further
      proliferation. Together, our data show that rat and human neurospheres have
      unique characteristics with regard to growth and differentiation, and that the
      majority of precursor cells within neurospheres are regionally specified to
      generate set numbers of neurons. These findings have important implications for
      understanding the nature of proliferating neural precursors isolated from the
      developing CNS, and their potential for brain repair.

PMID- 11947937
TI  - Induction of neuronal type-specific neurogenesis in the cerebral cortex of adult
      mice: manipulation of neural precursors in situ.
AB  - Over the past 3 decades, research exploring potential neuronal replacement
      therapies have focused on replacing lost neurons by transplanting cells or
      grafting tissue into diseased regions of the brain [Nat. Neurosci. 3 (2000) 67
      78]. Over most of the past century of modern neuroscience, it was thought that
      the adult brain was completely incapable of generating new neurons. However, in
      the last decade, the development of new techniques has resulted in an explosion
      of new research showing that neurogenesis, the birth of new neurons, normally
      occurs in two limited and specific regions of the adult mammalian brain, and that
      there are significant numbers of multipotent neural precursors in many parts of
      the adult mammalian brain [Mol. Cell. Neurosci. 19 (1999) 474-486]. Recent
      findings from our laboratory demonstrate that it is possible to induce
      neurogenesis de novo in the adult mammalian brain, particularly in the neocortex
      where it does not normally occur, and that it may become possible to manipulate
      endogenous multipotent precursors in situ to replace lost or damaged neurons
      [Nature 405 (2000) 951-955; Neuron 25 (2000) 481-492]. Recruitment of new neurons
      can be induced in a region-specific, layer-specific, and neuronal type-specific
      manner, and newly recruited neurons can form long-distance connections to
      appropriate targets. Elucidation of the relevant molecular controls may both
      allow control over transplanted precursor cells and potentially allow the
      development of neuronal replacement therapies for neurodegenerative disease and
      other central nervous system injuries that do not require transplantation of
      exogenous cells.

PMID- 11947938
TI  - Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains
      of mice.
AB  - The output potential of proliferating populations in either the developing or the
      adult nervous system is critically dependent on the length of the cell cycle
      (T(c)) and the size of the proliferating population. We developed a new approach
      for analyzing the cell cycle, the 'Saturate and Survive Method' (SSM), that also
      reveals the dynamic behaviors in the proliferative population and estimates of
      the size of the proliferating population. We used this method to analyze the
      proliferating population of the adult dentate gyrus in 60 day old mice of two
      inbred strains, C57BL/6J and BALB/cByJ. The results show that the number of cells
      labeled by exposure to BUdR changes dramatically with time as a function of the
      number of proliferating cells in the population, the length of the S-phase, cell
      division, the length of the cell cycle, dilution of the S-phase label, and cell
      death. The major difference between C57BL/6J and BALB/cByJ mice is the size of
      the proliferating population, which differs by a factor of two; the lengths of
      the cell cycle and the S-phase and the probability that a newly produced cell
      will die within the first 10 days do not differ in these two strains. This
      indicates that genetic regulation of the size of the proliferating population is
      independent of the genetic regulation of cell death among those newly produced
      cells. The dynamic changes in the number of labeled cells as revealed by the SSM
      protocol also indicate that neither single nor repeated daily injections of BUdR
      accurately measure 'proliferation.'

PMID- 11947939
TI  - Analysis of the temporal expression of nestin in human fetal brain derived
      neuronal and glial progenitor cells.
AB  - Nestin expression in the developing human brain was examined with the use of
      unique human specific anti-nestin antibodies. Double immunostaining of cell
      cultures and tissue sections derived from first and second trimester human fetal
      brain (HFB) examined the co-expression of nestin with other cell type specific
      phenotypic markers. The immunocytochemical analysis shows that from first to
      second trimester, the majority of developing glial cells exhibited a transitional
      state marked by co-expression of nestin and GFAP. However, the corresponding
      transitional state for developing neuronal cells, co-expressing nestin and MAP-2,
      was rarely detected. These results imply different temporal patterns of nestin
      expression in cells of glial and neuronal lineages. Confocal microscopy of HFB
      tissue section staining also revealed a similar pattern of nestin co-expression
      with glial and neuronal markers. Our results suggest that nestin expression alone
      may not identify an undifferentiated stem cell, and that progenitor cells in
      glial and neuronal lineages express nestin in different temporal patterns.

PMID- 11947940
TI  - Role of mitochondria in serum withdrawal-induced apoptosis of immortalized
      neuronal precursors.
AB  - The intracellular mechanisms controlling apoptosis in immature neurons are still
      largely unknown. Taking immortalized hippocampal neuronal precursors (mouse cell
      line HN9.10e) as a model, we have analyzed the cellular events associated to
      apoptosis induced by serum deprivation. We observed translocation of Bax from
      cytosol to mitochondria after 1 h of serum withdrawal followed, 2 h later, by
      cytochrome c release from mitochondria. These events occurred without
      mitochondrial membrane potential loss nor mitochondrial calcium raise. As calcium
      is implicated in several cell death pathways, we analyzed intracellular calcium
      levels after longer periods of serum deprivation. After 6 h, an increase of
      cytosolic Ca2+ was detected in HN9.10e cells loaded with the Ca2+ indicator Fluo3
      AM. This increase of calcium preceded morphological signs of apoptosis such as
      cell shrinkage and nuclear fragmentation, and was followed by a more pronounced
      raise that persisted until the terminal phases of the apoptotic process. Cells
      serum-deprived for 4 h and then grown in complete medium for 20 h fully recovered
      viability. Summarizing, in HN9.10e cells, calcium deregulation occurs in the late
      phases of apoptosis; earlier events involve translocation of Bax, release of
      cytochrome c, and maintenance of mitochondrial functionality. This allows an
      enlargement of the temporal window in which commitment to death is reversible.

PMID- 11947941
TI  - Expansion of mammalian neural stem cells in bioreactors: effect of power input
      and medium viscosity.
AB  - Multipotent neural precursors can be cultured in suspension bioreactors as
      aggregates of stem cells and progenitor cells. However, it is important to limit
      the size of the aggregates, as necrotic centers may develop at very large
      diameters. Previously, we have shown that the hydrodynamics within a suspension
      bioreactor can be used to control the diameter of NSC aggregates (D(MAVG)<150
      microm) below sizes where necrosis would be expected to occur. In the present
      study, power law correlations were developed for our bioreactors showing the
      dependence of the maximum mean aggregate diameter on both the kinematic viscosity
      of the medium and the power input per unit mass of medium. The power input was
      manipulated by changing the agitation rate (60-100 rpm), and the viscosity was
      manipulated through the addition of non-toxic levels of carboxymethylcellulose.
      The study also confirmed that the maximum liquid shear generated at the surface
      of the aggregates was sufficient to dislodge single cells, thus limiting the
      maximum diameter of the aggregates, without causing cell damage (tau(max)=9.76
      dyn/cm(2)). This is a first step in the development of a reproducible, scaled-up
      process for the production of neural stem cells for therapeutic applications
      including the treatment of neurodegenerative disorders and acute central nervous
      system injuries.

PMID- 11947942
TI  - Insulin-like growth factor-I and neurogenesis in the adult mammalian brain.
AB  - In most brain regions of highly developed mammals, the majority of neurogenesis
      is terminated soon after birth. However, new neurons are continually generated
      throughout life in the subventricular zone and the dentate gyrus of the
      hippocampus. Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that
      has demonstrated effects on these progenitor cells. IGF-I induces proliferation
      of isolated progenitors in culture, as well as affecting various aspects of
      neuronal induction and maturation. Moreover, systemic infusion of IGF-I increases
      both proliferation and neurogenesis in the adult rat hippocampus, and uptake of
      serum IGF-I by the brain parenchyma mediates the increase in neurogenesis induced
      by exercise. Neurogenesis in the adult brain is regulated by many factors
      including aging, chronic stress, depression and brain injury. Aging is associated
      with reductions in both hippocampal neurogenesis and IGF-I levels, and
      administration of IGF-I to old rats increases neurogenesis and reverses cognitive
      impairments. Similarly, stress and depression also inhibit neurogenesis, possibly
      via the associated reductions in serotonin or increases in circulating
      glucocorticoids. As both of these changes have the potential to down regulate IGF
      I production by neural cells, stress may inhibit neurogenesis indirectly via
      downregulation of IGF-I. In contrast, brain injury stimulates neurogenesis, and
      is associated with upregulation of IGF-I in the brain. Thus, there is a tight
      correlation between IGF-I and neurogenesis in the adult brain under different
      conditions. Further studies are needed to clarify whether IGF-I does indeed
      mediate neurogenesis in these situations.

PMID- 11947943
TI  - Migration patterns and phenotypic differentiation of long-term expanded human
      neural progenitor cells after transplantation into the adult rat brain.
AB  - We have examined long-term growth-factor expanded human neural progenitors
      following transplantation into the adult rat brain. Cells, obtained from the
      forebrain of a 9-week old fetus, propagated in the presence of epidermal growth
      factor, basic fibroblast growth factor, and leukemia inhibitory factor were
      transplanted into the striatum, subventricular zone (SVZ), and hippocampus. At 14
      weeks, implanted cells were identified using antisera recognizing human nuclei
      and the reporter gene green fluorescent protein. Different migration patterns of
      the grafted cells were observed: (i) target-directed migration of doublecortin
      (DCX, a marker for migrating neuroblasts)-positive cells along the rostral
      migratory stream to the olfactory bulb and into the granular cell layer following
      transplantation into the SVZ and hippocampus, respectively; (ii) non-directed
      migration of DCX-positive cells in the grey matter in striatum and hippocampus,
      and (iii) extensive migration of above all nestin-positive/DCX-negative cells
      within white matter tracts. At the striatal implantation site, neuronal
      differentiation was most pronounced at the graft core with axonal projections
      extending along the internal capsule bundles. In the hippocampus, cells
      differentiated primarily into interneurons both in the dentate gyrus and in the
      CA1-3 regions as well as into granule-like neurons. In the striatum and
      hippocampus, a significant proportion of the grafted cells differentiated into
      glial cells, some with long processes extending along white matter tracts.
      Although the survival time was over 3 months in the present study a large
      fraction of the grafted cells remained undifferentiated in a stem or progenitor
      cell stage as revealed by the expression of nestin and/or GFAP.

PMID- 11947944
TI  - Behavior of human neural progenitor cells transplanted to rat brain.
AB  - Human neural stem/progenitor cells provide a useful tool for studies of neural
      development and differentiation, as well as a potential means for
      neuroreplacement therapeutic needs in the human CNS. Stem cells isolated from
      developing human central nervous system of 8-12-week fetuses were transplanted to
      the forebrain and cerebellum of young and adult rats after 14 days of in vitro
      expansion. Cells were labeled by bisbenzimide prior to transplantation without
      immunosuppression. Recipient brains were examined 10 and 20 days after
      transplantation. Labeled stem cells were found in the neocortex, lateral
      ventricle and caudate nucleus in the forebrain, and in the molecular layer,
      Purkinje cell layer, and granular layer of the cerebellum. Mitotically dividing
      stem cells were observed in graft core, confirming their proliferative potential
      in new microenvironment. Engrafted cells migrate through the parenchyme of
      striatum, along the ventricular ependymal layer and callosal fibers, some of them
      reaching the opposite hemisphere. Some cells migrating along the capillaries
      express glial acid fibrillary protein, demonstrating their differentiation into
      astrocytes. Grafted cells expressing calbindin were found in the Purkinje cell
      layer, suggesting their differentiation into the Purkinje cells. At the same
      time, some grafted cells were undifferentiated and expressed vimentin. Our
      results demonstrate that cultured human neural stem/progenitor cells migrate and
      differentiate into both neurons and astrocytes after transplantation to the rat
      forebrain or cerebellum of young and adult rats.

PMID- 11947945
TI  - Evaluation of progenitor cell cultures from human embryos for
      neurotransplantation.
AB  - Human neural stem cells (HNSCs) are used in studies of neural development and
      differentiation, and are regarded as an alternative source of tissue for neural
      transplantation in degenerative diseases. Selection and standardization of HNSC
      samples is an important task in research and clinical approaches. We evaluated
      embryonal brain matter obtained from human 8-12-week-old fetuses by means of flow
      cytometry on a panel including: nestin; vimentin; NeuN; GFAP; beta-tubulin III;
      CD56; N-Cad; OB-Cad; HLA-ABC; HLA-DR; CD34, and annexin. Samples from embryos of
      even the same gestation differ dramatically regarding neural cell development,
      their phenotype and viability. The samples containing the highest proportion of
      stem cells and multipotent progenitors of neural types, and the least of
      definitive cells and antigens of histocompatibility, were selected for further
      expansion in serum-free medium. Secondary phenotyping 14 days later revealed
      again a marked heterogeneity of the cultures. For the final culturing for 24 h in
      a serum-containing medium we selected only samples having following phenotype:
      nestin+, and vimentin+ no less than 25%; HLA-DR+ and CD34+ no more than 5%; GFAP+
      no more than 10%; beta-tubulin+ no more than 20%; CD56+, N-Cad+, OB-Cad+, HLA
      A,B,C+, and annexin+ no more than 15%; cell viability no less than 60%.
      Immunocytochemical study of selected samples proved that numerous neural stem
      cells, and neuro- and glioblasts necessary for transplantation were present. Our
      results demonstrate that the flow cytometry phenotyping allows the screening and
      standardization of HNSC samples for further expansion and transplantation.

PMID- 11947963
TI  - Troglitazone improves GLUT4 expression in adipose tissue in an animal model of
      obese type 2 diabetes mellitus.
AB  - Troglitazone has been shown to improve peripheral insulin resistance in type 2
      diabetic patients and animal models. We examined the effect of troglitazone on
      the expression of glucose transporter 4 (GLUT4) in muscle and adipose tissue from
      Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of obese type 2
      diabetes mellitus. In addition, the effects of troglitazone on GLUT4
      translocation and on glucose transport activity in adipocytes were also
      evaluated. Muscle and adipose tissues were isolated from 35-week-old male
      troglitazone-treated and untreated OLETF rats at a dose of 150 mg/kg per day for
      14 days. In skeletal muscle, the protein and mRNA levels of GLUT4 were not
      significantly different between OLETF and control rats and they were not affected
      by troglitazone. On the other hand, GLUT4 protein and mRNA levels in adipose
      tissue from OLETF rats were significantly decreased (P<0.01) compared with
      control rats and they were significantly increased (1.5-fold, P<0.01) by
      troglitazone. Troglitazone had no major effect on GLUT4 translocation in
      adipocytes, but it significantly increased (1.4-fold, P<0.05) the basal and
      insulin-induced amounts of GLUT4 in plasma membrane (PM) in adipocytes from OLETF
      rats. Consistent with these results, the basal and insulin-induced glucose
      uptakes in adipocytes from troglitazone-treated OLETF rats were significantly
      increased (1.5-fold, P<0.05) compared with untreated OLETF rats. Our results
      suggest that troglitazone may exert beneficial effects on insulin resistance by
      increasing the expression of GLUT4 in adipose tissue.

PMID- 11947964
TI  - Autonomic neuropathy in streptozotocin diabetic rats: effect of acetyl-L
      carnitine.
AB  - The present study was designed to characterize cardiac autonomic neuropathy in
      streptozotocin-induced (45 mg/kg i.v.) diabetic rat by analysis of heart rate
      variability (HRV), and to assess, in this model, the effects of treatment with
      acetyl-L-carnitine (ALC). Heart rate was reduced in diabetic rats (332+/-22 vs.
      411+/-35 beat per min; P<0.0001). This bradycardia was partly reversed with ALC
      (369+/-52 beat per min; P<0.05 vs. untreated). Both time- and frequency-domain
      parameters of HRV were significantly reduced in diabetic rats. The reduction of
      spectral power was around 50% at high frequencies and about 70% at low
      frequencies, suggesting a decrease of parasympathetic activity. Low/high
      frequency ratio was significantly decreased in diabetic rats suggesting decreased
      sympathetic tone, while nonlinear analysis indicated a reduction of the chaotic
      complexity of heart rate dynamics in diabetic rats. Standard deviation of heart
      rate in ALC-treated rats was significantly higher than in untreated diabetic rats
      (P<0.0001). ALC counteracts the reduction of the power spectrum observed in
      diabetic animals (P<0.0005) normalizing the spectra profile. ALC restored chaotic
      complexity of heart rate dynamics. These results on the whole indicate that both
      sympathetic and parasympathetic cardiac tone were reduced significantly in
      diabetic rats and that ALC treatment prevents the development of autonomic
      neuropathy in streptozotocin-induced diabetes in rats.

PMID- 11947965
TI  - Low lipoprotein lipase mass in preheparin serum of type 2 diabetes mellitus
      patients and its recovery with insulin therapy.
AB  - There exists lipoprotein lipase mass in preheparin serum, even though the
      activity is scarcely found. We studied the preheparin serum lipoprotein lipase
      mass levels (prehaparin LPL mass) in type 2 diabetes mellitus patients and the
      effect of insulin therapy on the levels of preheparin LPL mass. In 40 type 2
      diabetes mellitus patients, preheparin LPL mass were measured by the sandwich
      enzyme-linked immunosorbent assay (ELISA), and were compared with those of non
      diabetic healthy control. The correlation between preheparin LPL mass and
      Hemoglobin A(1c) (HbA(1c)), serum lipids were studied. Preheparin LPL mass were
      measured before and after insulin therapy. Preheparin LPL mass of type 2 diabetes
      mellitus patients was significantly lower than that of non-diabetic healthy
      control. In diabetic patients, preheparin LPL mass were negatively correlated
      with HbA(1c). Fifteen patients started to take insulin therapy. Preheparin LPL
      mass increased significantly at 4th week, when fasting blood glucose decreased.
      These results suggested that preheparin LPL mass was greatly regulated by insulin
      action.

PMID- 11947966
TI  - Evaluation of insulin resistant diabetes mellitus in Alstrom syndrome: a long
      term prospective follow-up of three siblings.
AB  - Alstrom syndrome is a rare cause of diabetes mellitus. We studied two generations
      of a Turkish family in whom four members were affected by Alstrom syndrome. The
      natural course of the syndrome in three sisters was followed for 13 yr. The three
      sisters had short stature and truncal obesity, and developed complete blindness
      due to retinitis pigmentosa at 10, 5 and 13 yr of age. Two had sensorineural
      hearing loss and mild mental retardation, while the other developed diabetic
      ketoacidosis (DKA) at 14 yr and was treated with insulin from onset of diabetes.
      In the second case, diagnosis of diabetes was made by an OGTT at age 20 yr, and
      controlled with diet alone for 11 yr, then with a sulphonylurea for 2.5 yr, then
      with insulin. The third case developed acute hyperglycaemia at 20 yr, and
      required insulin from onset. Moreover, transitional features of impaired
      carbohydrate and fat metabolism (severe hyperinsulinaemia and insulin resistance
      progressing to islet beta cell failure, and hypertriglyceridaemia with fatty
      liver) were demonstrated, in accord with the literature. Previously unreported
      findings characteristic of nephro-uropathy with early-onset hypertension were
      also detected, and included in all cases proteinuria, glomerulopathy, and
      abnormal locations of the kidneys, narrowed uretero-renal junctions and dilated
      ureters.

PMID- 11947967
TI  - Diabetes in Ghana: a community based prevalence study in Greater Accra.
AB  - Data on the prevalence of diabetes in Ghana is scanty and unreliable. In the
      present study we have ascertained the prevalence of diabetes, impaired fasting
      glycaemia (IFG) and impaired glucose tolerance (IGT) in a random cluster sample
      of Ghanaians aged 25 years and above from the Greater Accra area of Ghana.
      Diabetes, IFG and IGT were defined by criteria of the American Diabetes
      Association and World Health Organization. The mean age of the 4733 subjects
      involved in the study was 44.3+/-14.7 years, and participation rate was 75%. The
      crude prevalence of diabetes was 6.3%. Out of 300 subjects with diabetes, 209
      (69.7%) had no prior history of the disease. Diabetes, IGT and combined IFG and
      IGT increased with age. The oldest age group (64+ years) had the highest diabetes
      prevalence (13.6%). The age-adjusted prevalence of diabetes, IFG and IGT, were
      6.4, 6.0 and 10.7%, respectively. Diabetes was more common in males than females
      (7.7 vs. 5.5%) [P<0.05]. Worsening glycaemic status tended to be associated with
      increase in age, body mass index, systolic and diastolic blood pressures.
      Ascertainment of predictors for diabetes in Ghanaians and the significance of the
      relatively high rates of and IFG and IGT however, remain to be determined.

PMID- 11947968
TI  - Process measures and outcome research as tools for future improvement of diabetes
      treatment quality.
AB  - OBJECTIVE: Good metabolic control, careful monitoring of late diabetic
      complications and early intervention against cardiovascular risk factors improve
      the prognosis in Type 1 and Type 2 diabetic patients. The aim of the present
      study was to analyse the treatment quality in a routine outpatient clinic.
      DESIGN: A descriptive survey of unselected outpatient Type 1 diabetic patients
      followed from 1995 to 1997. SETTING: The outpatient clinic at Steno Diabetes
      Center, Denmark. SUBJECTS: 2011 unselected Type 1 diabetic patients,
      representatives for the County of Copenhagen, Denmark. MAIN OUTCOME AND MEASURES:
      Levels of metabolic control, screening frequencies for late diabetic
      complications and cardiovascular risk factors. RESULTS: The mean age (SD) and
      diabetes duration of the patients were 49 (16) (SD) and 20 (13) years,
      respectively, and 54% of the patients were males. Glycosylated haemoglobin A(1c)
      (HbA(1c)) was measured at least once yearly in >99.5% of the patients, and the
      annual number of measurements was 3 pt(-1). The mean HbA(1c) (normal 4.1-6.4%)
      was 8.8, 8.7 and 8.6% in 1995, 1996, 1997, respectively. The frequency of
      HbA(1c)<140% of the non-diabetic mean (HbA(1c)<7.5%) was 14.6, 15.4 and 17.7% in
      the 3 years (P<0.05). Urinary albumin excretion was measured in 87.0, 87.1 and
      80.5%, and blood pressure in 71.4, 76.7 and 79.8% in the 3 years, respectively.
      In the 3-year period, foot examination and fundus photography were performed at
      least once in 84.7 and 88.6%, respectively. CONCLUSIONS: in unselected Type 1
      diabetic patients followed at the outpatient clinic at Steno Diabetes Center,
      only some, but not all, important clinical variables are measured at high
      frequency despite standard operation procedures. Continuous collection of data
      may help to explain why there is such a difference.

PMID- 11947969
TI  - Prevalence of latent autoimmune diabetes of adults (LADA) in Southern Spain.
AB  - OBJECTIVE: To study the prevalence of diabetes mellitus and islet autoantibodies
      in an adult population from Southern Spain. RESEARCH AND METHODS: A cross
      sectional study in Southern Spain of 1226 people, age 18-65 years. Clinical data
      were obtained and a blood sample taken to measure autoantibodies (glutamic acid
      decarboxylase antibodies (GADAb), tyrosine phosphatase antibodies (IA2Ab), and
      insulin antibodies (IAA)). An oral glucose tolerance test (OGTT) was also given
      to 982 of the subjects. RESULTS: The overall prevalence of diabetes mellitus
      according to the WHO 1979 criteria was 10.9% and according to the ADA 1997
      criteria it was 14.7% (8.8% were unaware of their diabetes). The prevalence of
      impaired fasting glucose (IFG) was 12.4% and of impaired glucose tolerance (IGT)
      11.5%. The prevalence of GADAb+ in the general population was 0.9% and in the
      diabetic population 3.7%. There were no significant differences between groups in
      the prevalence of IA2Ab or IAA (both were 0.8% in the general population). Of the
      three autoantibodies studied, only GADAb were significantly different in the
      diabetic population (P=0.0006). CONCLUSIONS: The prevalence of Type 2 diabetes
      and LADA are high in the south of Spain.

PMID- 11947970
TI  - Type of diabetes and waist-hip ratio are important determinants of serum
      lipoprotein (a) levels in diabetic patients.
AB  - This cross-sectional study compared serum lipoprotein (a) [Lp(a)] concentrations
      in type 1 and type 2 diabetic subjects and examined the determinants of Lp(a)
      concentrations in both types of diabetes. Serum Lp(a) was measured in 26 type 1
      and 107 type 2 diabetic patients and 126 non-diabetic controls. HbA(1c), fasting
      lipids and urinary albumin were also assayed. Lp(a) concentrations were higher in
      both type 1 and type 2 diabetic patients compared with controls (P<0.0001 and
      P<0.0001, respectively), and were higher in type 1 than type 2 diabetic patients
      (P<0.05). Waist-hip ratio (WHR) was an independent determinant of Lp(a)
      concentrations in both type 1 and type 2 diabetes.

PMID- 11947972
TI  - Moritz Schiff and the history of open-chest cardiac massage.

PMID- 11947973
TI  - Quality of life in long-term survivors of out-of-hospital cardiac arrest.
AB  - STUDY OBJECTIVE: The quality of life in long-term survivors of out-of-hospital
      cardiac arrest may be a good outcome measure after resuscitation. Therefore, the
      psychosocial situation and quality of life in such patients after successful
      resuscitation was evaluated. METHODS: Patients with out-of-hospital cardiac
      arrest in a community referred to a single tertiary care centre were compared
      with matched controls. Quality of life was evaluated in 50 consecutive arrest
      cases (40 males, 10 females; 60+/-13 years) 5-68 months (mean 31.7) after
      resuscitation according to American Heart Association protocols. RESULTS: The
      Psychological General Well-being Index questionnaire indicated no significant
      differences in anxiety, depression, vitality, general well-being, or self-control
      between patients and controls. However, the Nottingham Health Profile
      questionnaire demonstrated significant decreases in physical mobility (14.5+/
      18.1 vs. 4.0+/-8.5, P=0.0001), energy levels (25.3+/-31.0 vs. 2.0+/-8.0,
      P=0.0001), emotional reactions (11.3+/-16.6 vs. 4.0+/-10.2, P=0.009), and sleep
      patterns (19.2+/-28.6 vs. 8.4+/-16.7, P=0.023) in the arrest patients. Little
      differences were measured with the Everyday-Life Questionnaire. 49 of the 50
      arrest patients judged their situation after resuscitation worth living; no
      significant changes in familial, and psychosocial parameters occurred.
      CONCLUSIONS: The quality of life was associated with few changes in psychosocial
      profile after successful resuscitation. The subjective negative factors bore
      little impact on the quality of daily living in our patients. Thus, continued
      efforts to improve out-of-hospital resuscitation measures for cardiac arrest are
      justified since long-term survivors can expect a good quality of life after
      successful resuscitation.

PMID- 11947974
TI  - Influence of early defibrillation on the survival rate and quality of life after
      CPR in prehospital emergency medical service in a German metropolitan area.
AB  - Early defibrillation by emergency medical personnel has been shown to improve
      survival in patients suffering from out-of-hospital cardiac arrest with
      ventricular fibrillation. Due to organisational differences it is difficult to
      compare results in various studies. Comparison of studies has been simplified by
      introduction of the Utstein template. After introduction of an early
      defibrillation program in Hamburg, we compared the patients being treated with
      early defibrillation by emergency medical technicians (EMTs) with patients being
      defibrillated by physicians in an out-of-hospital emergency service in a
      prospective study. All patients suffered from non EMT-witnessed ventricular
      fibrillation of cardiac origin. During 1 year, 103 patients were analyzed with
      respect to survival rate and quality of life. Of the 53 patients in the early
      defibrillation group (G1) 11 regained a palpable pulse at physicians' arrival,
      whereas all patients of the control group (G2) showed ventricular fibrillation.
      More patients treated with early defibrillation regained sinus rhythm without
      antiarrhythmics in the prehospital phase (G1: n=43 (86%); G2: n=32 (60%); P<0.05)
      and had a shorter in-hospital stay (G1: median, 23 days; range 5-51 days; G2:
      median 39, range 15-88 days; P<0.05). Twelve patients in G1 and 16 in G2 were
      discharged from hospital. The survival rate was similar in both groups (after 6
      months G1: n=12; G2: n=14, after 12 months G1: n=10; G2: n=13 and after 24 months
      G1: n=9; G2: n=10), and the quality of life according to Glasgow-Pittsburgh
      Cerebral Performance Category (CPC) and Overall Performance Category (OPC) scores
      also was comparable between groups. We conclude that early defibrillation
      provides a higher incidence of return of a spontaneous circulation, a reduced
      need for antiarrhythmics and shorter in-hospital treatment times in patients with
      out-of-hospital ventricular fibrillation.

PMID- 11947975
TI  - Characteristics and outcome among patients suffering from in hospital cardiac
      arrest in relation to the interval between collapse and start of CPR.
AB  - AIM: To describe survival after in-hospital cardiac arrest in relation to the
      interval between collapse and start of cardiopulmonary resuscitation (CPR).
      PATIENTS: All patients suffering in-hospital cardiac arrest in Sahlgrenska
      University Hospital in Goteborg, Sweden between 1994 and 1999 in whom
      resuscitative efforts were attempted and for whom the interval between collapse
      and start of CPR was known. METHODS: Prospective recording of various factors at
      resuscitation including the interval between collapse and start of CPR.
      Retrospective evaluation via medical records of patients' previous history,
      clinical situation prior to cardiac arrest and final outcome. RESULTS: Survival
      to discharge was 33% among the 344 patients in whom CPR was started within the
      first minute as compared with 14% among the 88 patients in whom CPR started more
      than 1 min after collapse (P=0.008). The corresponding figures for patients found
      in ventricular fibrillation was 50 versus 32% (NS); for patients found in
      pulseless electrical activity 9 versus 3% (NS) and for patients found in asystole
      19 versus 0% (NS). Correcting for dissimililarties in the previous history and
      factors at resuscitation, the adjusted odds ratio and 95% confidence limits for
      being discharged from hospital when CPR was started within 1 min compared with a
      later start was 3.06 with 95% confidence limits of 1.59-6.31. CONCLUSION: Among
      patients with in-hospital cardiac arrest in whom the interval between collapse
      and start of CPR was known, we found that in 80% of the cases CPR was started
      within the first minute after collapse. Among these patients, survival to
      discharge was twice that of patients in whom CPR was started later. These results
      highlight the importance of immediate CPR after in-hospital cardiac arrest.

PMID- 11947976
TI  - Teaching hand placement for chest compression--a simpler technique.
AB  - BACKGROUND: Simplification of the techniques and teaching of resuscitation are
      advocated as ways of improving skill acquisition and retention. A simple method
      for teaching hand placement for chest compression has been described but not
      validated. OBJECTIVE: The objective of this study was to determine if instructing
      trainees simply to place their hands in the centre of the chest results in better
      initial and retained accuracy of hand placement than the usual method of first
      identifying anatomical landmarks. METHODS: Volunteers received instruction in
      basic CPR, being taught hand placement either by the standard method (33
      subjects) or the simplified method (32 subjects). They were tested for accuracy
      of hand position before training, immediately afterwards and 6 weeks later.
      RESULTS: After training both groups showed an improvement in accuracy of hand
      placement but there was no significant difference in the degree of improvement
      between the groups (P=0.345), nor in the level of accuracy achieved (P=0.178).
      Six weeks after training, the Standard Group demonstrated a statistically
      significant deterioration in accuracy (P=0.001), whereas the Simple Group did not
      (P=0.561). By this time, however, there was no longer any difference in accuracy
      of hand placement for either group compared with before training (Standard Group
      P=0.912; Simple Group P=0.140). On the positive side, the Simple Group took
      significantly less time (2.90 s) than the Standard Group (4.43 s) to change from
      ventilation to chest compression (P=0.000003). CONCLUSIONS: Simplifying the
      teaching of correct hand placement for chest compression does not appear to lead
      to improvement in acquisition or retention of the skill. However, it does result
      in a significant reduction in the length of the pauses between ventilation and
      chest compression.

PMID- 11947977
TI  - Evaluation of a new method for the carotid pulse check in cardiopulmonary
      resuscitation.
AB  - BACKGROUND: The ability to determine the presence or absence of a central pulse
      remains a key skill in cardiopulmonary resuscitation (CPR) for healthcare
      providers, despite studies showing that they perform this poorly. The aim of this
      study was to evaluate a modified technique for palpation of the carotid pulse.
      METHODS: Sixty seven undergraduate dental students were taught the standard
      method of carotid pulse detection during a basic life support session and were
      also taught a modified method. Each student was asked to palpate the carotid
      pulse of a volunteer in two positions (neck neutral and neck extended) with the
      volunteer on the floor and on a trolley. The time taken to identify the pulse was
      measured and the scenarios compared. RESULTS: The time to detect the carotid
      pulse was reduced in three of the four scenarios (floor, neck extended P=0.0053,
      trolley neck neutral P=0.0070, trolley neck extended P=0.0024). The final
      scenario (floor, neck neutral) showed no improvement (P=0.36). CONCLUSION: The
      new method of carotid pulse palpation results in a more rapid determination of
      the carotid pulse when it is present in all positions except with the neck
      neutral on the floor. This will only be clinically significant if trauma is
      suspected.

PMID- 11947978
TI  - Equivalence of the standard monophasic waveform shocks delivered by automated
      external defibrillators?
AB  - OBJECTIVE: To study whether two different types of monophasic waveform shocks
      (i.e. monophasic damped sinusoidal [MDS] and monophasic truncated exponential
      [MTE] waveform shocks) are of equivalent efficacy. METHODS: Retrospective review
      of defibrillation efficacy and outcome in ventricular fibrillation/ventricular
      tachycardia (VF/VT) patients treated in the same EMS system with AEDs delivering
      either MDS waveform shocks (n=40) or MTE waveform shocks (n=40). RESULTS:
      Defibrillation efficacy of the first shock was 82.5% in the MDS group and 70% in
      the MTE group (P=0.19). Termination of VF by at least one of the first three
      shocks was found in 95 and 85% of the patients treated with MDS and MTE waveform
      shocks, respectively (P=0.22). Restoration of spontaneous circulation occurred in
      75% of the MDS group and 30% of the MTE group (P=0.0001). Hospital admission
      rates were 52.5% in the MDS group and 17.5% in the MTE group (P=0.001). Hospital
      discharge rates were 17.5% in the MDS group and 7.5% in the MTE group (P=0.18).
      CONCLUSIONS: Our data suggest disparity in efficacy between MDS waveform shocks
      and MTE waveform shocks. Furthermore, our findings should be taken into
      consideration when the issue of the control group(s) in future clinical trials on
      new waveforms is discussed.

PMID- 11947979
TI  - Neonatal resuscitation: toward improved performance.
AB  - BACKGROUND: As part of a continuous quality assurance process which we instituted
      in 1999, we review videotapes of selected high-risk deliveries at our hospital.
      We utilized our reviews to evaluate the occurrence of errors, and to evaluate
      team and leader functions during neonatal resuscitation. METHODS: We established
      accepted behavior for members of resuscitation teams and the team leader. The
      actual conduct of the resuscitation was judged against the standard of the
      guidelines of the Neonatal Resuscitations Program of the American Heart
      Association, and the American Academy of Pediatrics. The videotapes of
      resuscitations were reviewed, and significant deviations from accepted practices
      were noted, and discussed by a specifically developed quality assurance
      committee, including, whenever possible, the actual resuscitators. RESULTS: We
      were able to detect a number of problems, which included inappropriate leader and
      team member activities, inappropriate preparation, communication, and
      coordination, and made a number of changes to our practice. CONCLUSIONS: We
      believe that neonatal resuscitation may be improved by the provision of teaching
      about team and leader functions, encouraging debriefing following complicated
      resuscitations, developing a minimal form to be completed for any patient
      requiring compressions or epinephrine within the delivery room, and providing
      more direct observations regarding the actual conduct of resuscitation.

PMID- 11947980
TI  - The epidemiology of cardiac arrests in a Sydney hospital.
AB  - AIM: To examine the epidemiology of cardiac arrest (CA) in New South Wales (NSW),
      Australia, and a large teaching hospital in Sydney and to identify predictors of
      survival. METHODS: Data from the 1996/97 NSW inpatient statistics collection were
      analysed. Logistic regression was used to determine predictors of mortality from
      CA. RESULTS: In 1996/97 in public hospitals, Eastern Sydney Area Health Service
      (AHS) (47.5), and in private hospitals of Macleay-Hastings District Health
      Services (DHSs), recorded the highest crude CA rates in NSW with figures of 47.5
      and 21.3 per 10,000 hospital separations. Standardised CA rates were highest in
      Western Sydney, Illawara, Macleay-Hasting, Mid North Coast and Orana DHSs. Most
      CAs in hospital 'X' occurred after admission and 55.7% occurred in patients
      admitted with a non-cardiac principal diagnosis, mainly pneumonia. Acute
      myocardial infarction was the leading diagnosis (28.9%) in patients who suffered
      CA after admission. Only 32% of CA patients survived to discharge. Age above 65
      (odds ratio (OR)=2.284, P=0.006) had the highest effect on cardiac mortality. The
      longer the patients were in the intensive care unit (OR=0.997, P=0.037), the more
      likely they were to survive. CONCLUSION: We describe considerable variation in CA
      rates in NSW. The majority of hospital CAs occur at or soon after admission, and
      are associated with underlying non-cardiac conditions. Survival following
      hospital CA is low, but there may be preventable elements. Knowledge of risk
      factors and epidemiology of hospital CAs may help identify patients at risk of
      CA.

PMID- 11947981
TI  - Knowledge of the national emergency telephone number and prevalence and
      characteristics of those trained in CPR in Queensland: baseline information for
      targeted training interventions.
AB  - Members of the community contribute to survival from out-of-hospital cardiac
      arrest by contacting emergency medical services and performing cardiopulmonary
      resuscitation (CPR) prior to the arrival of an ambulance. In Australia there is a
      paucity of information of the extent that community members know the emergency
      telephone number and are trained in CPR. A survey of Queensland adults (n=4490)
      was conducted to ascertain current knowledge and training levels and to target
      CPR training. Although most respondents (88.3%) could state the Australian
      emergency telephone number correctly, significant age differences were apparent
      (P<0.001). One in five respondents aged 60 years and older could not state the
      emergency number correctly. While just over half the respondents (53.9%) had
      completed some form of CPR training, only 12.1% had recent training. Older people
      were more likely to have never had CPR training than young adults. Additional
      demographic and socio-economic differences were found between those never trained
      in CPR and those who were. The results emphasise the need to increase CPR
      training in those aged 40 and over, particularly females, and to increase the
      awareness of the emergency telephone number amongst older people.

PMID- 11947982
TI  - Plasma endothelin in patients with acute aortic disease.
AB  - PURPOSE AND BACKGROUND: We investigated the plasma levels of endothelin 1/2 in
      patients with acute symptoms relating to a known or newly diagnosed aortic
      aneurysm in order to investigate the possible role of peptides in the development
      of the disease. METHODS: Endothelin 1/2 plasma levels were determined in patients
      admitted to the emergency unit with suspected acute aortic disease. The history,
      type of aneurysm, outcome and laboratory findings were determined and compared to
      endothelin 1/2 levels collected on admission. RESULTS: In patients with ruptured
      aneurysm (n=27) or acute aortic dissection (n=18) the endothelin 1/2 median
      levels were higher 1.1 (25th and 75th quartile 0.7, 1.7) fmol/ml than in patients
      (n=20) with pre-existing aneurysm 0.7 (0.4, 1.1) fmol/ml (P=0.013). Patients who
      died had significantly higher endothelin levels 1.3 (0.8, 1.9) fmol/ml than the
      survivors 0.8 (0.5, 1.4) fmol/ml (P=0.04). In a logistic regression analysis,
      only a higher blood pressure on admission was an independent predictor of
      survival. CONCLUSION: Endothelin 1/2 levels are elevated in patients with acute
      dissection or ruptured aneurysm, but they are not an independent predictor of
      survival.

PMID- 11947983
TI  - Predicting the success of defibrillation by electrocardiographic analysis.
AB  - BACKGROUND: We investigated an electrocardiographic signal analysis technique for
      predicting whether an electrical shock would reverse ventricular fibrillation
      (VF) in an effort to minimize the damaging effects of repetitive shocks during
      CPR. METHODS AND RESULTS: An established model of CPR was utilized. VF was
      electrically induced in anesthetized 40 kg domestic pigs. Defibrillation was
      attempted after either 4 or 7 min of untreated VF. Failing to reverse VF, a 1 min
      interval of precordial compression and mechanical ventilation preceded each
      subsequent defibrillation attempt. The amplitude frequency spectrum of digitally
      filtered VF wavelets was computed with Fourier analysis during uninterrupted
      precordial compression from conventional right infraclavicular and left apical
      electrodes. Of a total of 34 electrical defibrillation attempts, 24 animals were
      restored to spontaneous circulation (ROSC). An amplitude spectrum analysis (AMSA)
      value of 21 mV Hz had a negative predictive value of 0.96 and a positive
      predictive value of 0.78. CONCLUSIONS: AMSA predicted when an electrical shock
      failed to restore spontaneous circulation during CPR with a high negative
      predictive value. This method potentially fulfills the need for minimizing
      ineffective defibrillation attempts and their attendant adverse effects on the
      myocardium.

PMID- 11947984
TI  - End tidal CO(2) is reduced during hypotension and cardiac arrest in a rat model
      of massive pulmonary embolism.
AB  - BACKGROUND: We investigated the effect of massive pulmonary embolism (MPE) on end
      tidal CO(2) (etCO(2)) and tested two hypotheses: (1) that etCO(2) can distinguish
      massive PE from hemorrhagic shock and (2) that PE with cardiac arrest reduces
      etCO(2) during resuscitation to a greater extent than arrhythmic cardiac arrest.
      METHODS: Anesthetized, mechanically ventilated rats (N=10 per group), were
      subjected to either graded PE (latex microspheres), or graded hemorrhagic shock
      to produce a final mean arterial blood pressure, (MAP) of 40 mmHg; a third group
      was subjected to surgical/anesthetic control conditions. Cardiac arrest was
      induced by the following methods: intravenous injection of a large bolus of
      microspheres in the PE group, aortic puncture in the hemorrhage group, and
      intravenous tetrodotoxin (TTX) to produce arrhythmic cardiac arrest in the
      control group. RESULTS: At a MAP of 40 mmHg, etCO(2) was significantly decreased
      in the PE group (18.3+/-1.9 torr) compared with both the hemorrhage (24.3+/-1.3)
      and the control group (35.0+/-1.3 torr; ANOVA P<0.001). The decreased etCO(2)
      occurred coincident with an increase in alveolar dead space fraction in the PE
      group. In the first minute of ventilation after cardiac arrest, the etCO(2) was
      significantly decreased in the PE group (6.5+/-0.9) versus both hemorrhage
      (16.5+/-1.1) and TTX (34.2+/-2.4 torr). CONCLUSIONS: Massive PE with shock
      decreases the etCO(2) and increases the dead space fraction to a greater extent
      than hemorrhagic shock at the same MAP. Cardiac arrest from PE is associated with
      extremely low etCO(2) readings during CPR.

PMID- 11947985
TI  - Moderate hypothermia alters interleukin-6 and interleukin-1alpha reactions in
      ischemic brain in mice.
AB  - Female C57BL/6 mice were decapitated and their brains were removed and cultured
      at either 37 or 33 degrees C for 48 h to investigate whether or not moderate
      hypothermia alters the cytokine reactions in the ischemic brain. The interleukin
      6 and interleukin-1alpha levels in the culture media were significantly elevated
      in a time-dependent manner. The interleukin-6 levels after the incubation at 33
      degrees C were significantly lower than those at 37 degrees C. The interleukin
      1alpha levels at 33 degrees C were significantly higher than those at 37 degrees
      C. The interleukin-1alpha levels incubated with interleukin-6 antibody were
      significantly higher than those without IL-6 antibody. At 37 degrees C, the mRNA
      expression of interleukin-6 was observed from 2 to 48 h after incubation, but the
      same expression of interleukin-1alpha was only detected until 12 h. Accordingly,
      the ischemic brain incubated at 33 degrees C showed a decreased interleukin-6
      production in comparison with that at 37 degrees C and the level of interleukin-6
      showed negative feedback for the production of interleukin-1alpha. The
      temperature should, therefore, be carefully considered when evaluating the
      cytokine reaction for cerebral ischemia.

PMID- 11947986
TI  - Rescue of a patient out of a grain container: the quicksand effect of grain.
AB  - Grain storage containers not only present inherent dangers to the operators, but
      also to the rescuers if someone falls in. Here we report the rescue of a patient
      from a grain container using a novel technique involving a cylinder placed around
      the patient. This allowed the grain to be sucked out from around the patient and
      enabled his rescue uninjured. The rescue action was complicated by acute chest
      pain in the patient while he was submerged in the grain, and a severe asthma
      attack in the emergency physician. The rescue and the dilemmas encountered are
      described together with a review of the relevant literature.

PMID- 11947987
TI  - Amiodarone used in successful resuscitation after near-fatal flecainide overdose.
AB  - We report the case of a 45-year-old woman who had ingested 2000 mg of flecainide
      with suicidal intent. She developed therapy-resistant ventricular fibrillation
      (VF) with cardiopulmonary arrest. Cardiopulmonary resuscitation and advanced life
      support were sustained for 64 min. Following intravenous amiodarone, the patient
      developed an effective spontaneous rhythm and resumed breathing. An amiodarone
      infusion was started and continued over a period of 72 h. She recovered
      completely after 5 days, leaving the hospital without neurological sequelae.
      Serum flecainide levels approximately 5 h post-ingestion were 850 mg/l. This case
      report confirms the value of amiodarone in drug-resistant VF, even when the cause
      may be another antiarrhythmic drug such as flecainide.

PMID- 11947988
TI  - Problems with mis-assembly of adult manual resuscitators.

PMID- 11947989
TI  - SQAB 2001: an abundance of riches.

PMID- 11947990
TI  - Habituation, memory and the brain: the dynamics of interval timing.
AB  - Memory decay is rapid at first and slower later-a feature that accounts for
      Jost's memory law: that old memories gain on newer ones with lapse of time. The
      rate-sensitive property of habituation-that recovery after spaced stimuli may be
      slower than after massed-provides a clue to the dynamics of memory decay. Rate
      sensitive habituation can be modeled by a cascade of thresholded integrator units
      that have a counterpart in human brain areas identified by magnetic source
      imaging (MSI). The memory trace component of the multiple-time-scale model for
      habituation can provide a 'clock' that has the properties necessary to account
      for both static and dynamic properties of interval timing: static proportional
      and Weber-law timing as well as dynamic tracking of progressive, 'impulse' and
      periodic interval sequences.

PMID- 11947991
TI  - Packet theory of conditioning and timing.
AB  - Packet theory is based on the assumption that the momentary probability of
      producing a bout or packet of responding is controlled by the conditional
      expected time function. Bouts of head entry responses of rats into a food cup
      appear to have the same characteristics across a range of conditions. The
      conditional expected time function is the mean expected time remaining until the
      next food delivery as a function of time since an event such as food or stimulus
      onset. The conditional expected time function encodes mean interval duration as
      well as the distribution form so that both the mean response rate and form of
      responding in time can be predicted. Simulations of Packet theory produced
      accurate quantitative predictions of: (1) the effect of reinforcement density
      (mean food-food interval) and distribution form on responding; (2) scalar
      variance in fixed interval responding; (3) CS-US and intertrial interval effects
      on the strength of conditioning; and (4) the effect of the ratio of cycle:trial
      time on the strength of conditioning.

PMID- 11947992
TI  - Behavioral pharmacology and timing.
AB  - Drug effects on temporally patterned behavior are often described under the
      rubric of rate dependency: the effect of a drug on behavior is related to the
      rate of behavior in the absence of the drug. Specifically, drugs increase low
      rate behavior and decrease high rate behavior. These same types of effects are
      interpreted in the timing literature, however, as selective changes in temporal
      discrimination. The present series of experiments arrange situations that allow
      divergent predictions based on the two interpretations. In one component of a
      multiple schedule, when the response key is lit blue, food is available after the
      houselight is presented for a short duration (5 s). In the other component of the
      multiple schedule, when the response key is lit green, food is available after
      the houselight is presented for a long duration (30 s). No food is available
      after intermediate durations. Specific focus is given to a neuropharmacological
      information-processing model of timing. Predictions were compared for drugs that
      are thought to affect the clock and memory stages in the model. The results do
      not generally lend support for the neuropharmacological interpretation of the
      scalar expectancy theory, but emphasize the need for an explanatory mechanism
      that is consistent with the empirical generalization of rate dependency.

PMID- 11947993
TI  - Temporal generalization and diffusion in forgetting.
AB  - Two processes may contribute to the decrement in discriminability with increasing
      temporal distance between the occasioning event and later choice. One is the
      length of the interval and the other is generalization decrement. In the model
      described by White and Wixted [J. Exp. Anal. Behav. 71 (1999) 91-113], choice was
      predicted by the relative payoff for correct delayed matching responses,
      conditional on the current value of the stimulus sampled from Thurstone-like
      probability distributions of the effect of the sample stimuli. In the model,
      discriminability decreased with increasing temporal distance because the variance
      of the distributions increased with time. However, White and Wixted did not
      specify the function relating variance to temporal distance. If a diffusion
      process is assumed, and if diffusion increases exponentially with time, the
      resulting forgetting function is a negative exponential. An additional process
      involves exponential generalization of remembering from one time to other times.
      Alternative diffusion functions result in hyperbolic or power forgetting
      functions. The combination of two exponential processes yields forgetting
      functions that are double exponential in form and which appear consistent with a
      wide range of data.

PMID- 11947994
TI  - Relative numerosity discrimination in the pigeon: further tests of the linear
      exponential-ratio model.
AB  - This study tested a model of how animals discriminate the relative numerosity of
      stimuli in successive or sequential presentation tasks. In a discrete-trials
      procedure, pigeons were shown one light for nf times and then another for nl
      times. Next they received food for choosing the light that had occurred the least
      number of times during the sample. At issue were (a) how performance varies with
      the interval between the two stimulus sets (the interblock interval) and the
      interval between the end of the sample and the beginning of the choice period
      (the retention interval); and (b) whether a simple mathematical model of the
      discrimination process could account for the data. The model assumed that the
      influence of a stimulus on choice increases linearly when the stimulus is
      presented, but decays exponentially when the stimulus is absent; choice
      probability is given by the ratio of the influence values of the two stimuli. The
      model also assumed that as the retention interval elapses there is an increasing
      probability that the ongoing discriminative process be disrupted and then the
      animal responds randomly. Results showed that increasing the interblock intervals
      reduced the probability of choosing the last stimulus of the sample as the least
      frequent one. Increasing the retention interval reduced accuracy without inducing
      any stimulus bias. The model accounted well for the major trends in the data.

PMID- 11947995
TI  - Input coding in animal and human associative learning.
AB  - Two appetitive conditioning experiments with rats investigated whether the degree
      of generalization between a compound and its component parts is fixed or
      variable. Both experiments used a two-stage transfer design. In Stage 1, the
      elemental groups learned that a compound and its component parts signaled the
      same outcome (i.e. C+, D+, CD+), whereas the configural groups learned that a
      compound and its component parts signaled different outcomes (i.e. C+, D+, CD-,
      where '+' is pellets and '-' is no pellets). In Stage 2, the rats were tested for
      reductions in generalization. Experiment 1 found no evidence that past configural
      learning reduced generalization when a new set of alike-treated A and B elements
      were presented in compound for the first time. Experiment 2 found no evidence
      that past configural learning reduced generalization when the stimuli of Stage 1
      were presented in a new C-, D-, CD+ relation. In contrast to findings with
      humans, these results suggest that past experience plays a minor role in how
      stimuli are encoded in animal conditioning.

PMID- 11947996
TI  - Associative interference between cues and between outcomes presented together and
      presented apart: an integration.
AB  - In recent years, 'stimulus competition' in the study of acquired behavior has
      referred exclusively to (a) associative competition between cues trained in
      compound (e.g. overshadowing and blocking). Rarely cited are older experiments
      cast in the verbal learning tradition, now complemented with data from humans and
      rats in Pavlovian preparations, that demonstrate (b) competition between cues
      separately trained with a common outcome (i.e. proactive and retroactive
      interference). Similarly neglected are numerous examples of (c) competition
      between outcomes separately trained with a common cue within the verbal learning
      literature (also proactive and retroactive interference) as well as within the
      Pavlovian literature (i.e. counterconditioning). Recent data demonstrate (d)
      competition between outcomes trained in compound, thereby completing the four
      cells of a 2x2 matrix (competing stimuli trained together vs. trained apart and
      the competing stimuli being cues or outcomes) which highlights the ubiquitous
      nature of associative stimulus interference/competition. Most contemporary
      theories of acquired behavior can account for the phenomena in one or at most two
      cells of this matrix. Whether a common mechanism underlies the phenomena in all
      four cells of the matrix is currently unclear, but until such time as data
      preclude a common mechanism, parsimony encourages efforts to develop a model that
      encompasses all four cells. Here we offer a tentative model that addresses all
      four cells, albeit with two processes.

PMID- 11947997
TI  - Measuring behavioral momentum.
AB  - The metaphor of behavioral momentum proposes that when ongoing operant behavior
      is disrupted, changes in response rate are directly related to a force-like
      aspect of the disruptor and inversely proportional to behavioral mass. Several
      data sets suggest that differential resistance to change between the components
      of a multiple schedule satisfies the requirements of a ratio scale and is
      additive when different disruptors and different dimensions of reinforcement are
      combined. Differential resistance also provides a basis for scaling force in
      relation to rate of food presentation between components as a disruptor, and for
      scaling mass in relation to food rate within a component as a reinforcer.
      Preference in concurrent chains with terminal links identical to multiple
      schedule components also meets the requirements of ratio-scale measurement, is
      additive when different dimensions of reinforcement are combined, and provides
      convergent measurement of behavioral mass.

PMID- 11947998
TI  - Reinforcement of variations and repetitions along three independent response
      dimensions.
AB  - Reinforcement was presented contingent upon human subjects simultaneously varying
      three dimensions of an operant response. The response was drawing rectangles on a
      computer screen. The dimensions were area of the rectangle, its location on the
      screen, and its shape. In Experiment 1, an experimental group was reinforced for
      satisfying the three-part variability contingency. A control group was equally
      reinforced for drawing rectangles but independently of levels of variability.
      Results showed that the experimental group varied significantly more along each
      of the dimensions than did the control group. In Experiment 2, another group of
      subjects was reinforced for repeating instances along one of the dimensions, e.g.
      repeatedly draw a rectangle in approximately the same location, while
      simultaneously varying along the other two dimensions. The subjects learned to
      satisfy these contingencies as well. These results show reinforcement
      simultaneously and independently controls the variability of three orthogonal
      dimensions of a response.

PMID- 11947999
TI  - Teaching and learning in a probabilistic prisoner's dilemma.
AB  - The prisoner's dilemma is much studied in social psychology and decision-making
      because it models many real-world conflicts. In everyday terms, the choice to
      'cooperate' (maximize reward for the group) or 'defect' (maximize reward for the
      individual) is often attributed to altruistic or selfish motives. Alternatively,
      behavior during a dilemma may be understood as a function of reinforcement and
      punishment. Human participants played a prisoner's-dilemma-type game (for points
      exchangeable for money) with a computer that employed either a teaching strategy
      (a probabilistic version of tit-for-tat), in which the computer reinforced or
      punished participants' cooperation or defection, or a learning strategy (a
      probabilistic version of Pavlov), in which the computer's responses were
      reinforced and punished by participants' cooperation and defection. Participants
      learned to cooperate against both computer strategies. However, in a second
      experiment which varied the context of the game, they learned to cooperate only
      against one or other strategy; participants did not learn to cooperate against
      tit-for-tat when they believed that they were playing against another person;
      participants did not learn to cooperate against Pavlov when the computer's
      cooperation probability was signaled by a spinner. The results are consistent
      with the notion that people are biased not only to cooperate or defect on
      individual social choices, but also to employ one or other strategy of
      interaction in a pattern across social choices.

PMID- 11948000
TI  - Group choice and individual choices: modeling human social behavior with the
      Ideal Free Distribution.
AB  - Group choice describes the behavioral phenomenon in which a group of individuals
      chooses between two behavioral alternatives over time and the Ideal Free
      Distribution (IFD) [Acta Biotheor. 19 (1970) 16] describes group choice analogous
      to individual choice and the matching law. Our experiments investigated the
      usefulness of IFD analyses of human group choice based on a procedure reported in
      Sokolowski et al. [Psych. Bull. Rev. 6 (1999) 157]. A group of humans distributed
      into two subgroups to receive points that could earn cash prizes. The
      participants aligned themselves into subgroups by choosing between two rows of
      chairs, two different colored cards, or two cyber-subgroups. Different methods of
      distributing points to participants showed that IFD matching was dependent on the
      method (i.e. sharing points evenly produced near IFD matching, but probabilistic
      point distribution produced more undermatching). In addition, the sensitivity
      measures of individual choices in the groups differed from the sensitivity of the
      groups' choices.

PMID- 11948001
TI  - Behavior analysis and neuroscience.
AB  - Darwin proposed a powerful functional principle-natural selection-to interpret
      phylogenetic diversity and complexity. Nevertheless, some 70 years elapsed before
      even biologists embraced his account. The triumph of natural selection required
      two additional factors: (a) biological mechanisms that implemented the functional
      principle (i.e. genetics); and (b) quantitative procedures that traced its
      cumulative effects (i.e. population genetics). Thorndike and, later, Skinner
      proposed a functional principle-selection by reinforcement-that interpreted
      ontogenetic diversity and complexity. This principle has been substantially
      refined by subsequent experimental and theoretical work and now provides an
      equally powerful functional account. However, a purely functional principle has
      once again not persuaded most scientists (apart from the behavior-analytic
      minority) that complex behavior can be understood by a selection principle. If
      the history of ontogeny recapitulates the history of phylogeny, the biological
      mechanisms that implement selection by reinforcement must be discovered and
      quantitative techniques that trace its effects must be devised. In short, the
      triumph of reinforcement may await the integration of behavior analysis with the
      neurosciences and the development of coordinated quantitative procedures. This
      article identifies specific interrelations with neuroscience that form the basis
      for a behavior-analytically faithful interpretation of reinforcement using neural
      network techniques. Implications for the architecture of networks and for the
      learning algorithm are emphasized.

PMID- 11948002
TI  - A tribute to John Gibbon.
AB  - This article provides an overview of the published research of John Gibbon. It
      describes his experimental research on scalar timing and his development of
      scalar timing theory. It also describes his methods of research which included
      mathematical analysis, conditioning methods, psychophysical methods and secondary
      data analysis. Finally, it describes his application of scalar timing theory to
      avoidance and punishment, autoshaping, temporal perception and timed behavior,
      foraging, circadian rhythms, human timing, and the effect of drugs on timed
      perception and timed performance of Parkinson's patients. The research of Gibbon
      has shown the essential role of timing in perception, classical conditioning,
      instrumental learning, behavior in natural environments and in neuropsychology.

PMID- 11948003
TI  - Comparison of the bioavailability of unequal doses of divalproex sodium extended
      release formulation relative to the delayed-release formulation in healthy
      volunteers.
AB  - Valproate formulations, divalproex sodium extended-release (ER) and the
      traditional divalproex sodium delayed-release (DR) formulations, are not
      bioequivalent. This study evaluated if ER QD regimens with 14 and 20% higher
      daily doses were equivalent to the corresponding DR BID regimens with respect to
      exposure (AUC) while achieving lower maximum concentration (C(max)) and higher
      minimum concentration (C(min)) values. This was a Phase I, multiple-dose,
      fasting, randomized, open-label, crossover design study in healthy adult
      volunteers (n=36). The two crossover comparisons of unequal total daily doses
      were: 1000 mg ER versus 875 mg DR and 1500 mg ER versus 1250 mg DR. For each of
      14 and 20% higher ER versus DR dose comparisons, the ER and DR regimens were
      equivalent with respect to AUC. Furthermore, the ER formulation achieved a lower
      C(max) central value and a higher C(min) mean than the corresponding values for
      the DR formulation. The mean peak-to-trough fluctuations of valproic acid plasma
      concentrations were 42-48% lower for the ER formulation compared with the DR. The
      higher ER doses were as well tolerated as DR, with a small number of adverse
      events that were non-serious in nature and mild in intensity. Therefore,
      increasing the once-daily ER dose 14-20% while converting from a total daily DR
      dose given twice-daily results in equivalent exposure with lower C(max) and
      higher C(min) values.

PMID- 11948004
TI  - Psychiatric complications in patients with epilepsy: a review.
AB  - At least 50-60% of patients with epilepsy develop psychiatric disturbances,
      particularly mood, anxiety, and psychotic disorders. This article, aimed at the
      non-psychiatric clinician, reviews the differential diagnosis and treatment of
      psychiatric disturbances in epilepsy and focuses on the evaluation of psychiatric
      phenomena relative to the ictal state or the periictal and interictal periods.
      Pharmacological and non-pharmacological therapies are reviewed. A final section
      discusses potential interactions between antiepileptic and psychiatric
      medications.

PMID- 11948005
TI  - Unequal development of thresholds for various phenomena induced by cortical
      stimulation in rats.
AB  - Electrical stimulation of sensorimotor cortical area was performed in 9-, 12-, 18
      , 25-, 35- and 90-day-old rats with implanted electrodes to establish threshold
      intensities of currents necessary to elicit four different motor or EEG
      phenomena. Two different stimulation frequencies (8 and 50 Hz) were used.
      Development of thresholds for stimulation-bound movements, spike-and-wave
      afterdischarges and clonic seizures accompanying these afterdischarges was
      similar: the lowest threshold was found in 18-, respectively, in 18- and 25-day
      old rats with the 8 and 50 Hz frequencies. Younger as well as older animals
      exhibited higher threshold intensities. The fourth phenomenon, transition into
      another, 'limbic' type of afterdischarges appeared only exceptionally in the
      youngest rats and its incidence increased whereas the threshold decreased with
      age. Higher frequency was more efficient in elicitation of limbic afterdischarges
      than the 8 Hz stimulation in rats aged 18 and more days. Our data represent a
      background for pharmacological studies and indicate the development of cortical
      excitability and of connections between the thalamocortical system and limbic
      structures.

PMID- 11948006
TI  - Topiramate as add-on drug in severe myoclonic epilepsy in infancy: an Italian
      multicenter open trial.
AB  - PURPOSE: This study was to evaluate the efficacy and safety of topiramate (TPM)
      in patients with severe myoclonic epilepsy in infancy (SMEI) and refractory
      seizures. METHODS: We performed a prospective multicentric open label add-on
      study in 18 patients (age 2-21 years, mean 9 years) with SMEI and refractory
      seizures of different types. TPM was added to one or two other baseline drugs and
      the efficacy was rated according to seizure type and frequency. RESULTS: TPM was
      initiated at a daily dose of 0.5-1 mg/kg, followed by a 2-week titration at
      increments of 1-3 mg/kg/24 h up to a maximum daily dose of 12 mg/kg. After a mean
      period of 11.9 months (range 2-24 months), three patients (16.7%) had 100% fewer
      seizures and ten patients (55.5%) had a more than 50% seizure decrease. In no
      patient there was a seizure worsening. Mild to moderate adverse events were
      present in four patients (22.2%), represented by weight loss, hypermenorrhoea,
      renal microlithiasis, nervousness and dysarthric speech. CONCLUSION: TPM may be a
      useful drug in patients with SMEI, being particularly effective against
      generalized tonic-clonic seizures. Further studies are needed to evaluate the
      early use of this drug in such a severe syndrome.

PMID- 11948007
TI  - Interaction between carbamazepine, zonisamide and voltage-sensitive Ca2+ channel
      on acetylcholine release in rat frontal cortex.
AB  - To clarify the mechanisms of action of antiepileptic drugs (AEDs), carbamazepine
      (CBZ) and zonisamide (ZNS), on exocytosis mechanisms, the present study
      determined the concentration-dependent action of CBZ and ZNS, as well as the
      interaction between these AEDs and voltage-sensitive Ca(2+) channel (VSCC)
      activity on basal, Ca(2+)- and K(+)-evoked acetylcholine (ACh) release in frontal
      cortex of freely moving rat using in vivo microdialysis. Perfusion with
      therapeutic-relevant concentrations of CBZ and ZNS increased basal ACh release,
      which was regulated by N-type VSCC predominantly and P-type VSCC weakly, whereas
      supratherapeutic-relevant concentrations of these AEDs reduced this release. The
      3.4 mM Ca(2+)-evoked release, which was regulated by N-type VSCC selectively, but
      not by P-type VSCC, was increased by therapeutic-relevant concentrations of CBZ
      and ZNS, whereas this release was reduced by supratherapeutic-relevant
      concentrations of them. The 50 mM K(+)-evoked release, which was regulated by P
      type VSCC predominantly and N-type VSCC weakly, was decreased by CBZ and ZNS, in
      a concentration-dependent manner. These findings indicate that the interplay
      between enhancement of basal ACh release and reduction of depolarization-related
      ACh release in the frontal cortex are at least partially involved in a common
      mechanism of antiepileptic action between CBZ and ZNS.

PMID- 11948008
TI  - Suppression of pilocarpine-induced ictal oscillations in the hippocampal slice.
AB  - Activation of muscarinic cholinergic receptors produces oscillations in the
      hippocampal slice that resemble the theta rhythm, but also may produce abnormal
      synchronous activity that is more characteristic of epileptiform activity. We
      used pilocarpine, a muscarinic agonist and convulsant, and an elevation in
      extracellular potassium (5-7.5 mM) to produce synchronous neuronal activity that
      was prolonged (>2 s) and mimicked synchronization noted during seizures in vivo
      (ictal activity). In the CA3 region of adult rat hippocampal slices, prolonged
      ictal oscillations consisted of rhythmic field potentials occurring at 4-10 Hz
      for up to 30 s (ictal duration) that occurred in a regular periodic pattern every
      12-166 s (ictal interval). The duration and interval between ictal oscillations
      were measured before and after application of drugs to define determinants of
      ictal occurrence. High threshold calcium channel antagonists (nifedipine and
      verapamil) blocked ictal activity. Release of calcium from intracellular stores
      also appeared to be important for ictal synchronization because ictal activity
      was blocked by dantrolene, an inhibitor of calcium release from intracellular
      stores, and by thapsigargin which blocks the ATPase that maintains intracellular
      calcium stores. These suppressive effects appeared to be postsynaptic because
      nifedipine, dantrolene, and thapsigargin had no effect on evoked fEPSPs.
      Enhancement of presynaptic inhibition by activation of GABA(B) or adenosine A(1)
      receptors suppressed ictal activity and depressed the amplitude of evoked
      population synaptic potentials. The results point to an important role for high
      threshold calcium channels and release of calcium from intracellular stores in
      addition to strength of synaptic connections in generation of prolonged
      oscillations that underlie seizure activity.

PMID- 11948009
TI  - Inhibitory role of the zona incerta in the pilocarpine model of epilepsy.
AB  - Recent experiments have suggested that the zona incerta might be regarded as a
      highly sensitive structure for seizure induction. This sensitivity has been
      linked to this structure's abundant expression of cholinergic receptors. Here we
      have decided to investigate the participation of the GABAergic system of the zona
      incerta, one of its major neurotransmitters with widespread projections to the
      neocortex, in the pilocarpine (Pilo) model of epilepsy. Stereotaxic
      administration of a GABA(A) agonist (muscimol), antagonist (bicuculline) or
      saline (controls) bilaterally into the zona incerta of adult male Wistar rats was
      performed 30 min prior to the systemic injection of pilocarpine. Animals were
      electroencephalographically and behaviorally monitored for seizure activity.
      Administration of muscimol had a pro-convulsant effect characterised by a higher
      percentage of animals developing SE with a shorter latency. Conversely,
      administration of bicuculline had a dose dependent anticonvulsant effect, with no
      animals displaying SE. Our results contribute to the further characterisation of
      the regulatory role of the zona incerta in seizure-related phenomena, suggesting
      that its modulation might be a relevant target for anticonvulsant strategies.

PMID- 11948010
TI  - Tiagabine in glial tumors.
AB  - RATIONALE AND PURPOSE: Preliminary reports have suggested a possible 'aetiology
      specific' efficacy of tiagabine (TGB) in patients with drug-resistant partial
      epilepsy (DRPE) related to cerebral glial tumors (GTs). This efficacy should be
      related to selective blocking of GAT-1 transporter by TGB. We presented our open
      label, add-on TGB experience in a group of patients with GTs, compared with other
      symptomatic DRPEs of different aetiology. MATERIAL AND METHODS: eleven patients
      with DRPE related to oligodendroglioma (six cases), astrocytoma (4) or multiform
      gliobastoma (1); 12 patients with DRPE related to a miscellanea of CNS lesions.
      TGB was added to previous AEDs, at dosage of 20-60 mg per die. Responders are
      defined by seizure frequency reduction >50% compared with baseline. RESULTS:
      Seven patients are responders with three seizure-free (SF) in GTs group, a rate
      of efficacy much higher than in matching group (63.6 vs. 16.6%). Adverse events
      have been observed only rarely, not leading to discontinuation, in GTs group.
      CONCLUSION: This preliminary observation seems to confirm the high efficacy and
      tolerability of TGB in DRPE related to GTs.

PMID- 11948011
TI  - Molecular forms of the estrogen receptor in breast cancer.
AB  - Estrogen receptors (ERs) of which two isoforms have been identified (alpha and
      beta) are subjected to phosphorylation, glycozylation, ubiquitination and other
      post-transcriptional conformational changes giving rise to a very high molecular
      heterogeneity. Partial proteolysis of these receptors, as well as their high
      tendency to associate within oligomeric structures, reinforces this property.
      Investigations demonstrated that this heterogeneity is not a biochemical artefact
      suggesting some biological relevance. Our purpose was to review this topic,
      especially with regard to ERalpha from breast cancers.

PMID- 11948012
TI  - Involvement of steroids and cytochromes P(450) species in the triggering of
      immune defenses.
AB  - In vertebrates the wide variety of cytochromes P(450) (P(450)) is a key for
      elimination of low molecular weight xenobiotics and for the production and
      metabolism of steroid hormones. In contrast, xenobiotics of large molecular
      weight are processed and eliminated after the immune response. The suppression of
      immune response by native P(450)-produced glucocorticoid (GC) hormones
      constitutes a first link between P(450) and immunity. In the last decade,
      mechanisms and molecules responsible for the triggering of immune response were
      investigated and results showed that many tissues and organs transform native
      3beta-hydroxysteroids into 7-hydroxylated metabolites that trigger immunity.
      Present data suggest that 7-hydroxysteroids are native anti-GCs that block the GC
      induced immunosuppression. Because specific P(450) are responsible for the
      production of 7-hydroxylated steroids resulting into increased immunity, a second
      link exists between P(450) and immunity. Taken together, these findings support
      the proposal that P(450) are keys to all of the known defense mechanisms of
      vertebrates against all xenobiotic forms.

PMID- 11948013
TI  - 17beta-Estradiol inhibits cytokine induction of the human E-selectin promoter.
AB  - Estradiol has been shown to decrease levels of the cell adhesion molecule E
      selectin in cultured cells and in women on hormone replacement therapy. We set
      out to determine if the mechanism of estradiol action on E-selectin is at the
      level of its promoter. It was found that estradiol repressed the cytokine
      stimulated induction of luciferase activity driven by the human E-selectin
      promoter in a reporter plasmid (hE-sel-LUC) in co-transfected human hepatoma
      cells (Hep G2) and human umbilical cord endothelial cells (ECV-304). Repression
      by estradiol was dependent on the presence of transfected estrogen receptor (ER)
      alpha or beta expression vectors. The ER antagonist ICI-182,780 blocked the
      repression by estradiol, confirming the receptor-dependence of the effect. The
      intact DNA-binding domain of ERalpha was required for estradiol repression of the
      cytokine-induced stimulation of the promoter in each cell line as demonstrated by
      the inability of an ER construct with two point mutations in the DNA-binding
      domain to inhibit reporter activity. Mutation of the NFK-B site at -94 to -85
      within the E-selectin promoter led to less stimulation of hE-sel-LUC by
      interleukin one beta (IL-1beta). Estradiol did not inhibit this IL-1beta
      stimulated luciferase activity, indicating that the NFK-B site is necessary for
      ER-mediated inhibition of this promoter. Mutation of the AP-1 site at -500 to 
      494 within the E-selectin promoter had no effect on the ability of IL-1beta to
      stimulate its transcription, and estradiol repressed this activation in an ER
      dependent manner with identical efficacy and potency in comparison with the wild
      type promoter. Therefore, the E-selectin promoter is down-regulated by estradiol
      working through either ERalpha or ERbeta and requires the NFK-B site at -94 to 
      85 within the promoter.

PMID- 11948014
TI  - The novel isoform of the estrogen receptor-alpha cDNA (ERalpha isoform S cDNA) in
      the human testis.
AB  - In order to clone the novel isoform of the cDNA for the human estrogen receptor
      alpha (ERalpha), the human testicular cDNA library was screened by the exons 4-8
      corresponding sequence of the human ERalpha cDNA. As a result, a novel isoform of
      the ERalpha cDNA (termed the ERalpha isoform S cDNA), which consists of a
      previously unidentified 5'-sequence and the exons 4-8 of the ERalpha gene, has
      been cloned. The structure of the ERalpha isoform S cDNA is essentially similar
      to that of the progesterone receptor (PR) isoform S cDNA that was identified in
      our recent report. Analysis of the genomic DNA revealed that the 5'-sequence of
      the ERalpha isoform S mRNA originated from a novel exon (termed the exon S).
      Moreover, the reverse transcription-polymerase chain reaction (RT-PCR) was
      carried out using the primers specific to the ERalpha isoform S mRNA on the total
      RNA from the human spermatozoon (Sp), liver (Li), uterine endometrium (Em) and
      myometrium (Mm). The ERalpha isoform S mRNA was detected in the uterine Em and
      Sp. Moreover, the molecular size of the ERalpha isoform S encoded by the ERalpha
      isoform S mRNA, which was analyzed by the transfection of the expression vector
      with ERalpha isoform S cDNA into the 293T cell, was approximately 39kDa. It was
      indicated that the one of the ATGs in the exon S could be used as the translation
      initiation codon. This is the first report on the ERalpha mRNA isoform that is
      not caused by exon-skipping or alternative utilization of the untranslated 5'
      exons.

PMID- 11948015
TI  - Expression of progesterone receptor isoforms A and B is differentially regulated
      by estrogen in different breast cancer cell lines.
AB  - Progesterone action in target tissues is mediated through two progesterone
      receptor (PR) isoforms, PR-A and PR-B, which display different regulatory
      functions in target cells. Relative expression ratio of these isoforms varies
      depending on cell and tissue types. Here, we studied the regulation of PR isoform
      expression by estradiol (E(2)), insulin, IGF-1 and cAMP in different breast
      cancer cell lines. Although, E(2) induced PR expression in all cell lines
      studied, the expression ratio of PR-A/PR-B induced by E(2) was dependent on the
      cell line. The differential regulation of the isoforms was also seen at the mRNA
      level suggesting that the PR-A and PR-B promoters are differentially regulated by
      E(2) in different breast cancer cells. Insulin, IGF-1 or cAMP previously reported
      to induce PR expression however failed to alter the PR expression in our study.
      This is the first report describing that in different breast cancer cell lines
      the expression of PR-A and PR-B is regulated by E(2) in a distinct way.

PMID- 11948016
TI  - Plasma 24,25-dihydroxyvitamin D concentration of Dahl salt-sensitive rats
      decreases during high salt intake.
AB  - Dahl salt-sensitive rats, but not salt-resistant rats, develop hypertension in
      response to high salt intake. We have previously shown an inverse relationship
      between plasma 25-hydroxyvitamin D (25-OHD) concentration and blood pressure of
      Dahl salt-sensitive rats during high salt intake. In this study, we report on the
      relationship between high salt intake and plasma 24,25-dihydroxyvitamin D (24,25
      (OH)(2)D) concentration of Dahl salt-sensitive and salt-resistant rats. Rats were
      fed a high salt diet (8%) and sacrificed at day 2, 7, 14, 21, and 28. Plasma
      24,25-(OH)(2)D concentrations of salt-sensitive rats were reduced to 50% of that
      at baseline at day 2-when blood pressure and plasma 25-OHD concentration were
      unchanged, but 25-OHD content in the kidney was 81% of that at baseline. Plasma
      24,25-(OH)(2)D concentration was reduced further to 10% of that at baseline from
      day 7 to 14 of high salt intake, a reduction that was prevented in rats switched
      to a low salt (0.3%) diet at day 7. Exogenous 24,25-dihydroxycholecalciferol
      (24,25-(OH)(2)D(3)), administered at a level that increased plasma 24,25-(OH)(2)D
      concentration to five times normal, did not attenuate the salt-induced
      hypertension of salt-sensitive rats. Plasma 24,25-(OH)(2)D concentration of salt
      resistant rats was gradually reduced to 50% of that at baseline at day 14 and
      returned to baseline value at day 28 of high salt intake. We conclude that the
      decrease in plasma 24,25-(OH)(2)D concentration in salt-sensitive rats during
      high salt intake is caused by decreased 25-OHD content in the kidney and also by
      another unidentified mechanism.

PMID- 11948017
TI  - Evidence that steroid 5alpha-reductase isozyme genes are differentially
      methylated in human lymphocytes.
AB  - The synthesis of dihydrotestosterone (DHT) is catalyzed by steroid 5alpha
      reductase isozymes 1 and 2, and this function determines the development of the
      male phenotype during embriogenesis and the growth of androgen sensitive tissues
      during puberty. The aim of this study was to determine the cytosine methylation
      status of 5alpha-reductase isozymes types 1 and 2 genes in normal and in 5alpha
      reductase deficient men. Genomic DNA was obtained from lymphocytes of both normal
      subjects and patients with primary 5alpha-reductase deficiency due to point
      mutations in 5alpha-reductase 2 gene. Southern blot analysis of 5alpha-reductase
      types 1 and 2 genes from DNA samples digested with HpaII presented a different
      cytosine methylation pattern compared to that observed with its isoschizomer
      MspI, indicating that both genes are methylated in CCGG sequences. The analysis
      of 5alpha-reductase 1 gene from DNA samples digested with Sau3AI and its
      isoschizomer MboI which recognize methylation in GATC sequences showed an
      identical methylation pattern. In contrast, 5alpha-reductase 2 gene digested with
      Sau3AI presented a different methylation pattern to that of the samples digested
      with MboI, indicating that steroid 5alpha-reductase 2 gene possess methylated
      cytosines in GATC sequences. Analysis of exon 4 of 5alpha-reductase 2 gene after
      metabisulfite PCR showed that normal and deficient subjects present a different
      methylation pattern, being more methylated in patients with 5alpha-reductase 2
      mutated gene. The overall results suggest that 5alpha-reductase genes 1 and 2 are
      differentially methylated in lymphocytes from normal and 5alpha-reductase
      deficient patients. Moreover, the extensive cytosine methylation pattern observed
      in exon 4 of 5alpha-reductase 2 gene in deficient patients, points out to an
      increased rate of mutations in this gene.

PMID- 11948018
TI  - Okadaic acid inhibits angiotensin II, adrenocorticotropin and potassium-dependent
      aldosterone secretion.
AB  - The present study was designed to assess the effect of okadaic acid (OA), a
      protein phosphatase inhibitor, on aldosterone secretion in response to
      angiotensin II (AII), adrenocorticotropin (ACTH) and rises in external potassium
      concentration (K+). AII (10nM) caused a 20-fold increase in aldosterone
      production and OA reduced this response by 45%. ACTH (10nM) caused an 8.6-fold
      increase in aldosterone secretion and OA reduced this by 83%. Increasing K+
      concentration from 3 to 12mM caused a 13-fold increase in aldosterone production,
      which OA inhibited by 36%. These results suggest that protein phosphatases
      participate in the control of adrenal steroid production, even though ACTH, AII
      and K+ act via different intracellular messenger systems.

PMID- 11948019
TI  - Nonsteroidal compounds designed to mimic potent steroid sulfatase inhibitors.
AB  - Chemical synthesis and enzyme inhibition results are reported for a series of
      nonsteroidal sulfatase inhibitors, 1-(p-sulfamoyloxyphenyl)-5-(p-t-butylbenzyl)-5
      alkanols and the lower active phenolic analogues. These compounds conserve some
      structural elements from the previously reported potent steroidal inhibitor 3-O
      sulfamate-17alpha-(p-t-butylbenzyl)-17beta-hydroxy-estra-1,3,5(10)-triene, while
      the C18-methyl group and the hydrocarbon backbone represented by the steroid
      rings B, C, and D were replaced with a free conformational chain. Using estrone
      sulfate (100 microM) as substrate and homogenate of transfected HEK-293 cells as
      source of steroid sulfatase activity, the IC(50) values of the best inhibitors,
      the undecanol derivatives, were 0.4+/-0.1 and >300 nM, respectively, in the
      sulfamate and phenolic series. Although these sulfamoylated nonsteroidal
      inhibitors appear a bit less active than their steroidal analogues, they are
      however more potent than known inhibitors estrone-3-O-sulfamate and p-(O
      sulfamoyl)-N-tetradecanoyl tyramine. The optimal side-chain length for the
      inhibition of steroid sulfatase activity was found to be six carbons, which
      corresponds to the number of carbons that mimic the B, C and D steroid rings,
      between C6 and C17. Furthermore, compounds with only the t-butylbenzyl group or
      the alkyl chain of six carbons are less potent inhibitors compared to the one
      that include both of these hydrophobic substituents. Such results suggest that
      compound from this later category better mimic the steroidal inhibitor.

PMID- 11948020
TI  - Effects of flavonoid phytochemicals on cortisol production and on activities of
      steroidogenic enzymes in human adrenocortical H295R cells.
AB  - Inhibitory effects of flavonoid phytochemicals, flavones, flavonols and
      isoflavones on cortisol production were examined in human adrenal H295R cells
      stimulated with di-buthylyl cAMP. In addition, the inhibitory effects of these
      chemicals on the activity of P450scc, 3beta-HSD type II (3beta-HSD II), P450c17,
      P450c21 and P45011beta, steroidogenic enzymes involved in cortisol biosynthesis,
      were examined in the same cells. Exposure to 12.5 microM of the flavonoids 6
      hydroxyflavone, 4'-hydroxyflavone, apigenin, daidzein, genistein and formononetin
      significantly decreased cortisol production (by 6.3, 69.6, 47.5, 26.6, 13.8 and
      11.3%, respectively), and biochanin A significantly decreased cortisol production
      (by 47.3%) at a concentration of 25 microM without any significant cytotoxic
      effects or changes in cell number. Daidzin, the 7-glucoside of daidzein, did not
      alter cortisol production by H295R cells at concentrations over 10 microg/ml (24
      microM). Daidzein-induced reduction of cortisol production by H295R cells was not
      inhibited by the estrogen receptor antagonist ICI 182,780. The flavonoids 6
      hydroxyflavone, daidzein, genistein, biochanin A and formononetin strongly and
      significantly inhibited microsomal 3beta-HSD II activity at concentrations from 1
      to 25 microM, and I(50) values were estimated to be 1.3, 2, 1, 0.5 and 2.7
      microM, respectively. In addition, these flavonoids significantly inhibited
      microsomal P450c21 activity at 12.5 and/or 25 microM. In addition, 6
      hydroxyflavone inhibited activity of microsomal P450c17 and mitochondrial
      P45011beta at 12.5 and/or 25 microM. Results of Lineweaver-Burk's plot analysis
      indicate that daidzein is a competitive inhibitor of the activity of 3beta-HSD II
      and P450c21. K(m) and V(max) values of 3beta-HSD II for DHEA were estimated to be
      6.6 microM and 328pmol/minmg protein, respectively. K(m) and V(max) values of
      P450c21 for progesterone were estimated to be 2.8 microM and 16pmol/minmg
      protein, respectively. K(i) values of 3beta-HSD II and P450c21 for daidzein were
      estimated to be 2.9 and 33.3 microM, respectively.

PMID- 11948021
TI  - The novel exon, exon T, of the human progesterone receptor gene and the genomic
      organization of the gene.
AB  - Recently, we have cloned the novel isoform of the progesterone receptor (PR) cDNA
      (PR isoform S cDNA) from the human testicular cDNA library. The isoform S cDNA
      consists of the novel exon (termed the exon S of the PR gene) and the exons 4-8
      of the PR gene. In order to investigate the existence of the other isoform of the
      human PR cDNA, the human testicular cDNA library was screened by the exons 4-8
      corresponding sequence of the human PR cDNA in the present study. As a result, we
      have identified a novel isoform of the PR cDNA (termed the PR isoform T cDNA (PR
      T cDNA)), which consisted of a previously unidentified 5'-sequence and the exons
      4-8 of the PR gene. The structure of this isoform T cDNA is essentially similar
      to that of the isoform S cDNA. By the genomic cloning, the 5'-sequence of the PR
      isoform T mRNA was demonstrated to originate from a novel independent exon, exon
      T, which was located in the 5'-upstream region of the exon S.

PMID- 11948022
TI  - What constitutes effective management of pneumothorax after CT-guided needle
      biopsy of the lung?

PMID- 11948023
TI  - The web also wheezes.

PMID- 11948024
TI  - Assessment of prognosis in idiopathic dilated cardiomyopathy.

PMID- 11948025
TI  - Balancing self and patient in the physician-patient relationship.

PMID- 11948026
TI  - Prevention and management of hypoxemia during fiberoptic bronchoscopy.

PMID- 11948027
TI  - Sleeping with the enemy: the heart in obstructive sleep apnea.

PMID- 11948028
TI  - Asthma and gastroesophageal reflux: another piece in the puzzle?

PMID- 11948029
TI  - Two-year retrospective economic evaluation of three dual-controller therapies
      used in the treatment of asthma.
AB  - OBJECTIVE: To compare asthma-related health-care utilization and expenditures for
      patients prescribed one of three dual-controller therapies: fluticasone plus
      salmeterol, inhaled corticosteroids (ICS) [excluding fluticasone] plus
      salmeterol, and ICS plus a leukotriene modifier (LTM). MATERIALS AND METHODS:
      Asthma-related medical claims from two major health plans were obtained for the
      12 months before and after the initiation of dual therapy. A total of 1,325
      patients > or = 12 years old with no claims for COPD or respiratory tract cancer
      were selected from the approximately 3.5 million lives covered. Multivariable
      regression was used to assess differences in asthma-related expenditures. To
      compensate for positive skew, all cost variables were log-transformed. RESULTS:
      Risk-adjusted total asthma-related costs for the fluticasone-plus-salmeterol
      cohort (n = 121), the ICS-plus-salmeterol cohort (n = 844), and the ICS-plus-LTM
      cohort (n = 360) [corrected] were $975, $1,089, and $1,268, respectively. Risk
      adjusted pharmacy costs were $813, $841, and $996, respectively. Generalized
      linear modeling, controlling for baseline covariates, indicated that compared to
      ICS-plus-LTM therapy, fluticasone-plus-salmeterol therapy was associated with a
      significant reduction in asthma-related total (p = 0.0014) and pharmacy (p =
      0.001) costs. Similar results were found when the ICS-plus-salmeterol group and
      the ICS-plus-LTM group were compared (p = 0.0001). The number of inpatient,
      outpatient, and emergency department visits and their corresponding costs were
      lower for the fluticasone-plus-salmeterol cohort, but were not statistically
      significant (p > 0.05). CONCLUSION: Results from managed-care practice suggest
      that treatment with fluticasone plus salmeterol, and more broadly ICS plus
      salmeterol, yield important cost savings when compared to treatment with ICS plus
      LTM.

PMID- 11948030
TI  - A comparison of albuterol administered by metered-dose inhaler and spacer with
      albuterol by nebulizer in adults presenting to an urban emergency department with
      acute asthma.
AB  - STUDY OBJECTIVES: To determine the efficacy of albuterol by metered-dose inhaler
      (MDI) and spacer compared to a nebulizer. DESIGN: A prospective, open-label
      study. SETTING: Large urban emergency department (ED). PATIENTS: All consecutive
      adult asthma patients over a 2.5-year period. INTERVENTIONS: ED personnel used a
      standardized treatment algorithm, which included albuterol administered by
      nebulization, for patients presenting to the ED during the first 12 months of the
      study. The treatment algorithm then was switched to one that utilized albuterol
      administered by MDI/spacer as the primary mode of delivery for the following 18
      months. As part of the conversion to MDI/spacer, ED staff counseled patients on
      self-management and supplied patients with a peak flowmeter, an MDI/spacer, and
      an inhaled steroid for home use. MEASUREMENTS: Pulmonary function, clinical
      outcome, laboratory data, and financial data were assembled and analyzed from
      2,342 ED visits and 1,420 patients. RESULTS: While there was no significant
      difference in hospital admission rates between patients in the MDI/spacer group
      and the nebulizer group (13.2% and 14.6%, respectively), there was a
      statistically greater improvement in peak flow rates in the MDI/spacer group
      (126.8 vs 111.9 L/min, respectively; p = 0.002). The MDI/spacer group also spent
      significantly less time in the ED (163.6 and 175 min, respectively; p = 0.007),
      had a lower total albuterol dose (1,125 microg and 6,700 microg, respectively; p
      < 0.001), and showed a greater improvement in arterial oxygen saturation (p =
      0.043). Relapse rates at 14 and 21 days were significantly lower (p < 0.01 and p
      < 0.05, respectively) among patients treated with the MDI/spacer and were
      associated with asthma education and the provision of a peak flowmeter, a spacer,
      and an inhaled corticosteroid for patients' home use. CONCLUSIONS: Albuterol
      administered by MDI/spacer is an efficacious and cost-effective alternative to
      nebulization in adults with acute asthma who present at a large urban ED.

PMID- 11948031
TI  - Response of lung volumes to inhaled salbutamol in a large population of patients
      with severe hyperinflation.
AB  - OBJECTIVES: Current criteria use FEV(1) to assess bronchodilator responsiveness,
      despite its insensitivity and inability to predict improvement in symptoms or
      exercise tolerance. Response in lung volumes remains largely unexplored even
      though volume parameters, such as inspiratory capacity (IC), closely correlate
      with functional improvements. Therefore, we assessed the response of lung volumes
      (i.e., by IC, total lung capacity [TLC], functional residual capacity [FRC],
      residual volume [RV], and FVC) to salbutamol and the relationship of these
      changes to improvements in the spirometry in these patients. DESIGN: A
      retrospective review of data extracted from a large database of patients who were
      undergoing spirometry and static lung volume measurements before and after the
      administration of 200 microg salbutamol. PATIENTS: Patients with an FEV(1)/FVC
      ratio of < 85% of predicted values were defined as being severely hyperinflated
      (SH) if TLC was > 133% of predicted and as being moderately hyperinflated (MH) if
      TLC was 115 to 133% of predicted. RESULTS: Two hundred eighty-one SH patients and
      676 MH patients were identified. Salbutamol significantly reduced the mean (+/-
      SEM) TLC (SH patients, 222 +/- 23 mL; MH patients, 150 +/- 10 mL; p < 0.001), FRC
      (SH patients, 442 +/- 26 mL; MH patients, 260 +/- 39 mL; p < 0.001), and RV (SH
      patients, 510 +/- 28 mL; MH patients, 300 +/- 14 mL; p < 0.001) and increased
      both the IC (SH patients, 220 +/- 15 mL; MH patients, 110 +/- 11 mL; p < 0.001)
      and FVC (SH patients, 336 +/- 21 mL; MH patients, 204 +/- 13 mL; p < 0.001).
      FEV(1) improved in a minority of patients (SH patients, 33%; MH patients, 26%),
      but if lung volume measurements are also considered, the overall bronchodilator
      response may improve to up to 76% of the SH group and up to 62% of the MH group.
      Changes in volumes correlated poorly with changes in maximal airflows.
      CONCLUSIONS: Bronchodilators reduce hyperinflation. Measurements of lung volumes
      before and after bronchodilators add sensitivity when examining for
      bronchodilator responsiveness.

PMID- 11948032
TI  - A comparison of the validity of different diagnostic tests in adults with asthma.
AB  - STUDY OBJECTIVES: Diagnosing asthma is not always easy, and there are times when
      objective tests can be helpful. The extent to which these tests alter the
      probability of asthma depends on how much more commonly the test result is
      positive in subjects with asthma compared to healthy subjects and particularly
      subjects with conditions that are commonly confused with asthma. We set out to
      compare the sensitivity and specificity of different tests in this setting.
      DESIGN: Single-center, cross-sectional, observational study. SETTING: Teaching
      hospital. PATIENTS: Twenty-one healthy control subjects, 69 patients with asthma,
      and 20 subjects referred to the hospital with a diagnosis of asthma who were
      found to have alternative explanations for their symptoms (i.e., pseudoasthma).
      INTERVENTIONS: We measured methacholine airway responsiveness, the maximum within
      day peak expiratory flow amplitude mean percentage (derived from twice-daily
      readings for > 2 weeks), the FEV(1)/FVC ratio, the percentage change in FEV(1) 10
      min after the administration of 200 microg inhaled albuterol, and the
      differential eosinophil count in blood and induced sputum. We derived normal
      ranges (from the 95% upper or lower limit for healthy subjects), sensitivity, and
      specificity (ie, the percentage of subjects with pseudoasthma who had negative
      test results). RESULTS: Most tests were less specific when the reference
      population was composed of subjects with conditions that can be confused with
      asthma. Methacholine airway responsiveness and the sputum differential eosinophil
      count were the most sensitive (91% and 72%, respectively) and specific (90% and
      80%, respectively) tests. CONCLUSION: We conclude that methacholine airway
      responsiveness and the sputum differential eosinophil count are the most useful
      objective tests in patients with mild asthma.

PMID- 11948033
TI  - Comparison of the efficacy, tolerability, and safety of formoterol dry powder and
      oral, slow-release theophylline in the treatment of COPD.
AB  - STUDY OBJECTIVE: To compare the efficacy, tolerability, and safety of therapy
      with formoterol and oral slow-release theophylline (THEO) in patients with COPD.
      DESIGN: A randomized, parallel-group study, with double-blind arms for formoterol
      and placebo (PL) and an open arm for oral slow-release THEO administered in
      individual doses on the basis of plasma concentrations. SETTING: Eighty-one
      centers worldwide. PATIENTS: Eight hundred fifty-four patients with symptomatic
      COPD. INTERVENTION: Comparison of twice-daily inhaled formoterol dry powder (12
      or 24 microg), PL, and THEO (individualized doses) over 12 months. MEASUREMENTS
      AND RESULTS: Compared to PL, doses of formoterol and THEO both significantly
      improved the area under the curve for FEV(1) measured over a period of 12 h
      following the morning dose of study medication at 3 and 12 months (p < 0.001 for
      all comparisons). Therapy with formoterol, 12 microg, was significantly more
      effective than that with THEO (p < or = 0.026). Formoterol significantly reduced
      the percentage of "bad days" (i.e., days with at least two individual symptom
      scores > or = 2 and/or a reduction in peak expiratory flow from a baseline of >
      20%; p < or = 0.035 vs. PL and THEO), and the use of salbutamol rescue medication
      (p < or = 0.003 vs PL) over the whole treatment period, while the effect of THEO
      was similar to that of PL. Therapy with formoterol and THEO was more effective
      than PL at improving quality of life for > 12 months (p < or = 0.030). Treatment
      related adverse events and discontinuations were more frequent among patients
      receiving THEO than among those receiving formoterol. CONCLUSIONS: Long-term
      treatment with inhaled formoterol dry powder is more effective and better
      tolerated than treatment with therapeutically appropriate doses of oral slow
      release THEO in symptomatic patients with COPD.

PMID- 11948034
TI  - Megestrol acetate stimulates weight gain and ventilation in underweight COPD
      patients.
AB  - STUDY OBJECTIVES: To assess the effect of megestrol acetate (MA), a
      progestational appetite stimulant commonly used in patients with AIDS and cancer,
      on body weight and composition, respiratory muscle strength, arterial blood gas
      levels, and subjective perceptions in COPD patients. DESIGN AND SETTING:
      Prospective, double-blind, randomized, placebo-controlled trial conducted on an
      outpatient basis at 18 sites. PATIENTS: Underweight (< 95% ideal body weight)
      COPD patients > or = 40 years old. INTERVENTIONS: Either MA, 800 mg/d oral
      suspension, or placebo at a 1:1 ratio for 8 weeks. RESULTS: Of 145 randomized
      patients (63% men), 128 patients completed the trial. Body weight increased by
      3.2 kg in the MA group and 0.7 kg in the placebo group (p < 0.001).
      Anthropometric and dual-energy radiograph absorptiometry assessments confirmed
      that weight gain was mainly fat. Spirometry and maximal voluntary ventilation
      showed no significant changes from baseline in either group, and the difference
      in the change in maximum inspiratory pressure between groups was not significant.
      The 6-min walk distances did not differ statistically between groups at week 2
      and week 4, but were greater in the placebo group at week 8 (p = 0.012).
      Consistent with the known ability of MA to stimulate ventilation, PaCO(2)
      decreased (4.6 mm Hg, p < 0.001) and PaO(2) increased (2.8 mm Hg, p < 0.04) in
      the MA group. Questionnaires revealed that body image and appetite improved in
      the MA group but not the placebo group. Adverse event frequency and type were
      similar in both groups, but cortisol and testosterone (in men) levels decreased
      substantially in the MA group. CONCLUSIONS: We conclude that MA safely increased
      appetite and body weight, stimulated ventilation, and improved body image in
      underweight COPD patients, but did not improve respiratory muscle function or
      exercise tolerance.

PMID- 11948035
TI  - Isokinetic muscle function in COPD.
AB  - AIM: Exercise limitation in patients with COPD has been attributed to impaired
      ventilation and reduced skeletal muscle function. We have previously used a
      combination of FEV(1) and leg muscle function (work achieved during a 30-s
      isokinetic sprint test) to predict progressive exercise capacity. However, the 30
      s test may not be well tolerated in patients with advanced lung disease. We
      studied the relationship between progressive exercise capacity, FEV(1), and
      isokinetic work in patients with COPD and in healthy control subjects to assess
      whether the work accomplished at time intervals of < 30 s could also be used to
      predict progressive maximal exercise capacity (Wmax). METHODS: Twenty-seven
      patients with COPD and 29 control subjects underwent anthropometric measures,
      spirometry, progressive cycle ergometry, and 30-s isokinetic cycling. RESULTS:
      There was no significant difference for weight, height, or body mass index
      between the groups. The COPD group was slightly older and had a significantly
      lower FEV(1) than control subjects. They also had a lower Wmax (56 +/- 28.3 W vs
      141.9 +/- 46.7 W) and isokinetic work accomplished over 10 s (W10), over 15 s
      (W15), over 20 s (W20), over 25 s (W25), and over 30 s (W30). Wmax correlated in
      both patients with COPD and in control subjects with W10, W15, W20, W25, W30, and
      FEV(1). Combining FEV(1) and isokinetic work (W10, W15, W20, W25, or W30) in a
      two-factor model to predict Wmax, the coefficients of determination (r(2)) for
      patients with COPD were 0.57, 0.57, 0.58, 0.59, and 0.58, and for control
      subjects were 0.69, 0.69, 0.71, 0.71, and 0.73, respectively. Wmax correlated
      with weight only in control subjects. CONCLUSIONS: Both ventilatory function and
      leg muscle function contribute to exercise limitation, and a 20-s isokinetic test
      can be utilized to assess leg function in patients with COPD.

PMID- 11948036
TI  - An evaluation of two approaches to exercise conditioning in pulmonary
      rehabilitation.
AB  - STUDY OBJECTIVES: To compare the effectiveness of two forms of exercise training
      in pulmonary rehabilitation. DESIGN: A prospective, randomized, unblinded, 8-week
      trial. SETTING: A hospital-based outpatient pulmonary rehabilitation program.
      PATIENTS: Forty patients (20 patients in each group) with COPD who were referred
      for pulmonary rehabilitation. INTERVENTIONS: We compared the short-term
      effectiveness of a high-intensity, lower-extremity endurance program with a low
      intensity, multicomponent calisthenics program for the rehabilitation of patients
      with COPD. The high-intensity group trained predominately on the stationary
      bicycle and treadmill, with a goal of exercising at > or = 80% of maximal level
      determined from incremental testing for 30 min per session. The low-intensity
      group performed predominately classroom exercises for approximately 30 min per
      session. For both groups, twice-weekly sessions were held for 8 weeks. The
      primary outcome measure was health status, measured using the Chronic Respiratory
      Disease Questionnaire. Other outcomes included peak oxygen consumption on
      incremental treadmill exercise testing, exertional dyspnea, treadmill endurance
      time, the number of sit-to-stand repetitions and arm lifts in 1 min, overall
      dyspnea, and questionnaire-rated functional status. MEASUREMENTS AND RESULTS:
      Both groups showed significant postrehabilitation improvement in exercise
      variables, exertional and overall dyspnea, functional performance, and health
      status. Patients in the high-intensity group showed greater increases in
      treadmill endurance and greater reductions in exertional dyspnea, whereas those
      in the low-intensity group showed greater increases in arm-endurance testing.
      Both groups had similar improvements in overall dyspnea, functional performance,
      and health status. CONCLUSIONS: Despite differences in exercise performance, both
      high-intensity, lower-extremity endurance training and low-intensity calisthenics
      led to similar short-term improvements in questionnaire-rated dyspnea, functional
      performance, and health status.

PMID- 11948037
TI  - Power of outcome measurements to detect clinically significant changes in
      pulmonary rehabilitation of patients with COPD.
AB  - STUDY OBJECTIVES: Several validated instruments are used to measure outcomes,
      such as exercise performance, dyspnea, and health-related quality of life after
      pulmonary rehabilitation (PR) in patients with COPD. However, no study has
      simultaneously compared the responsiveness of the most frequently used outcome
      measurements after PR. We designed this study to investigate the capacity of
      several of the most frequently used outcome measurements to detect changes after
      PR in a population of patients with severe COPD who qualified for lung volume
      reduction surgery. DESIGN, PATIENTS, AND INTERVENTIONS: We evaluated 37 patients
      with severe COPD (FEV(1) < 40%) before and after 6 to 8 weeks of outpatient PR.
      The following frequently used tools were evaluated: the 6-min walk distance
      (6MWD); functional dyspnea with the Medical Research Council (MRC) scale;
      baseline and transitional dyspnea index (BDI/TDI); resting and 6MWD visual analog
      scale (VAS); quality of life with a generic tool (the Short Form-36 [SF-36]); and
      two disease-specific tools, the Chronic Respiratory Disease Questionnaire (CRQ)
      and the St. George's Respiratory Questionnaire (SGRQ). RESULTS: After PR, mean +/
      SD 6MWD increased in 33 of 37 patients (89%), from 285 +/- 97 to 343 +/- 92 m (p
      = 0.009). Improvements were seen also in the MRC scale in 23 of 37 patients (62%;
      from 2.27 +/- 0.8 to 1.86 +/- 0.6; p = 0.01); in CRQ dyspnea in 25 of 37 patients
      (67%; from 3.25 +/- 0.9 to 3.90 +/- 1.4; p = 0.02); in CRQ mastery in 22 of 37
      patients (60%; from 4.37 +/- 1.4 to 5.14 +/- 1.3; p = 0.01); and in BDI/TDI
      functional in 24 of 37 patients (64%; from 1.4 +/- 0.8 to 0.7 +/- 1.1; p =
      0.002). There were smaller improvements in the SGRQ in 18 of 37 patients (48%)
      and in the SF-36 in 19 of 37 patients (51%), but they were not statistically
      significant. There were good correlations between the dyspnea components of all
      the tools. The 6MWD change did not correlate with the changes in the other
      outcomes. Clinically significant changes in the values for those outcome tools
      were detected in > 50% of patients for the BDI/TDI, 29% of patients for the MRC
      scale, in 37% of patients for the 6MWD, in 48% of patients for the VAS at peak
      exercise, in > 50% of patients for the CRQ, and in 40% of patients for the SGRQ.
      CONCLUSIONS: We conclude that the VAS peak exercise, BDI/TDI, and CRQ adequately
      reflect the beneficial effects of PR. The 6MWD evaluates a unique domain not
      related to quality of life. Due to their simplicity and sensitivity, VAS at peak
      exercise, 6MWD, and CRQ may be the best practical tools to evaluate
      responsiveness to PR.

PMID- 11948038
TI  - Comparison of the peak exercise response measured by the ramp and 1-min step
      cycle exercise protocols in patients with exertional dyspnea.
AB  - STUDY OBJECTIVES: To compare the peak exercise response and determine the limits
      of agreement between the ramp and the 1-min step cycle protocols in a
      representative population of patients with exertional breathlessness attending a
      respiratory outpatient clinic. DESIGN: Crossover with the test order double
      blinded and randomized. SETTING: Outpatient exercise physiology laboratory.
      PATIENTS: Twenty-two patients (12 men; mean [SD] age, 59 [8] years; FEV(1), 71%
      [21%]) with lung disease and/or exertional breathlessness. INTERVENTION: Symptom
      limited, maximum cycle exercise tests using a ramp and a 1-min step work rate
      (WR) protocols. The two protocols were assigned to subjects in a randomized
      manner. MEASUREMENTS AND RESULTS: Oxygen uptake (O(2)), minute ventilation (E),
      heart rate (HR), WR, exercise time, and Borg scores were compared at symptom
      limited peak exercise. The mean (SD) peak values for the ramp and the step
      protocols, respectively, were as follows: peak O(2), 1.51 (0.44) L/min and 1.49
      (0.43) L/min; peak E, 50.8 (12.9) L/min and 49.9 (14.5) L/min; and peak HR, 133
      (24) beats/min and 131 (22) beats/min (p > 0.05). There were no significant
      differences between breathlessness and perceived exertion at peak exercise. Peak
      WR (WRpeak) and exercise time were significantly higher using the ramp protocol:
      110.5 (37.1) W vs 105.6 (35.6) W, and 8.2 (2.0) min vs. 7.6 (1.9) min,
      respectively. CONCLUSIONS: The ramp protocol leads to a higher WRpeak, and this
      may have implications for exercise prescription. However, there were no
      significant differences between the two protocols for the peak physiologic
      responses. The choice of protocol for the measurement of maximal exercise
      capacity remains one of laboratory preference.

PMID- 11948039
TI  - Stair climbing test predicts cardiopulmonary complications after lung resection.
AB  - STUDY OBJECTIVE: To evaluate the capability of the stair climbing test to predict
      cardiopulmonary complications after lung resection for lung cancer. DESIGN: A
      prospective cohort of candidates for lung resection. Spirometric assessment and
      the stair climbing test were performed the day before operation. Univariate and
      multivariate analyses were performed to identify predictors of postoperative
      complications. SETTING: Tertiary referral center. PATIENTS: A consecutive series
      of 160 candidates for lung resection with lung carcinoma from January 2000
      through March 2001. RESULTS: At univariate analysis, the patients with
      complications were significantly older (p = 0.02), had a significantly lower
      FEV(1) percentage (p = 0.007) and predicted postoperative FEV(1) percentage (p =
      0.01), had a greater incidence of a concomitant cardiac disease (p = 0.02),
      climbed a lower altitude at the stair climbing test (p < 0.0001), and had a lower
      calculated maximum oxygen consumption (O(2)max) [p = 0.03] and predicted
      postoperative O(2)max (p = 0.006) compared to the patients without complications.
      At multivariate analysis, the altitude reached at the stair climbing test
      remained the only significant independent predictor of complications.
      CONCLUSIONS: The stair climbing test is a safe and economical exercise test, and
      it was the best predictor of cardiopulmonary complications after lung resection.

PMID- 11948040
TI  - Prolonged endurance challenge at moderate altitude: effect on serum eosinophil
      cationic protein, eosinophil dynamics, and lung function.
AB  - BACKGROUND: Eosinophils contain granule proteins such as eosinophil cationic
      protein (ECP) that have proinflammatory effects on airways. ECP may be released
      on activation of eosinophils into the plasma and is widely used as a marker of
      bronchial hyperreactivity and allergic inflammation. Environmental factors as
      well as intense physical exertion may influence eosinophil-related bronchial
      hyperreactivity. STUDY OBJECTIVES: To investigate the effect of endurance
      exercise at moderate altitude on levels of circulating eosinophils, serum ECP,
      serum osmolality (sOS), and dynamic pulmonary function parameters in healthy
      mountaineers. SETTING: Alpine field study performed in the Alps of Upper Styria
      in Austria. Type of exercise: Ascent of a mountain at maximal speed.
      PARTICIPANTS: Thirty healthy male volunteers from a troop of military
      mountaineers. RESULTS: Mean ECP concentration increased by 66% at the summit
      checkpoint (H2) and remained at 63% above baseline (base checkpoint [H0]) after
      descent (H4), while the blood eosinophil count decreased concomitantly from
      250/microL at H0 (preexercise) to 118/microL (53%) at H2 and to 22/microL (81%)
      at H4. The total serum ECP concentration adjusted to sOS correlated negatively
      with blood eosinophil count (r = - 0.37; p < 0.0001) and PaO(2) (r = - 0.34; p <
      0.001), but positively with the peak expiratory flow (PEF) [r = 0.45; p <
      0.0001]. Although sOS correlated with serum ECP at H2 (r = 0.47; p = 0.02) and at
      12 h after the start of the experiment (H12) [r = 0.57; p = 0.003], the
      relationship between total ECP and sOS (r = 0.19; p = 0.034) was less pronounced.
      FEV(1) in percentage of FVC (%FEV(1)/FVC) [the Tiffenau test], forced expiratory
      flow rate at 25% of vital capacity, and PEF were significantly higher at H2 than
      at H0 and H4. %FEV(1)/FVC decreased to 88% (p < 0.01) and 83% (p < 0.001)
      predicted at H12 and 24 h after start of the experiment, respectively.
      CONCLUSION: Results provide strong evidence for nonspecific activation of blood
      eosinophils during prolonged intense aerobic exercise at moderate altitude,
      modifying both eosinophil dynamics and regulation of ECP release in healthy
      subjects.

PMID- 11948041
TI  - Effects of an intensive 4-week summer camp on cystic fibrosis: pulmonary
      function, exercise tolerance, and nutrition.
AB  - STUDY OBJECTIVES: Cystic fibrosis (CF) patients prefer exercise to most other
      forms of therapy, although objective improvement remains controversial. Israeli
      CF patients have attended a summer program in Switzerland for many years with
      subjective improvement. However, CF camps worldwide have been cancelled recently,
      due to fears of cross-infection with resistant organisms. Therefore, we evaluated
      the effect of attending the camp on pulmonary function, exercise tolerance, and
      nutritional state in CF patients. DESIGN: Weight, resting pulmonary function,
      incremental exercise test results, and sputum culture findings were assessed
      before and after a 4-week intensive summer camp. SETTING: Davos, Switzerland
      (altitude, 1,500 m). PATIENTS: Thirteen Israeli CF patients (seven women and six
      men) with an age range of 9 to 25 years who had mild-to-moderate lung disease. No
      patients had Burkholderia cepacia detected in their sputum. INTERVENTIONS: The
      program included a high-calorie diet, chest physiotherapy, daily mountain
      climbing, and indoor activities. Arterial oxygen saturation (SaO(2)) was
      maintained at > 88% during exertion. RESULTS: Exercise tolerance improved
      significantly. The peak work capacity increased by 12.7%, the maximal oxygen
      uptake increased by 10%, and minute ventilation increased by 18.5% (p < 0.0005).
      Of the calculated parameters, the anaerobic threshold improved by 17%.
      Ventilation was always the limiting factor during exercise, although it improved.
      There was no significant change in resting lung function and pulse or in SaO(2)
      decline at maximal exercise. The mean weight gain was 1 kg. No patient acquired B
      cepacia. CONCLUSIONS: An intensive summer camp improved exercise tolerance and
      nutrition in CF patients. This may explain improved patient well-being despite
      unchanged values for resting lung function. The reinstitution of summer camps,
      with special care to avoid cross-infection, should be considered.

PMID- 11948043
TI  - Chronic cough due to gastroesophageal reflux disease: failure to resolve despite
      total/near-total elimination of esophageal acid.
AB  - BACKGROUND: While medical therapy may fail to improve cough due to
      gastroesophageal reflux disease (GERD), it is not known if inadequate esophageal
      acid suppression is responsible. METHODS: In a prospective, before-and-after
      interventional trial, we assessed the effects of antireflux surgery in eight
      patients whose chronic coughs were due to GERD resistant to intensive medical
      therapy. All patients met a profile predicting that cough was likely due to GERD
      and had an initial positive 24-h esophageal pH monitoring study, and then
      underwent serial 24-h esophageal pH monitoring on gradually intensified medical
      therapy until the percentage of time that esophageal pH was < 4 was zero and
      there were no acid reflux events > 4 min. The effects of medical and surgical
      therapy on cough were assessed clinically by a visual analog scale (VAS) and the
      Adverse Cough Outcome Survey (ACOS). RESULTS: Before surgery (median, 23.7 days),
      patients still complained of cough, VAS score was 73.1 +/- 6.1, and ACOS score
      was 15.0 +/- 1.1. After surgery (median, 41.2 days and 1 year), cough improved in
      all, VAS score decreased to 19.1 +/- 8.3 and 22.6 +/- 8.1 (p = 0.001),
      respectively, and ACOS score decreased to 2.0 +/- 1.3 and 3.6 +/- 2.3,
      respectively (p = 0.002). CONCLUSIONS: Antireflux surgery can improve chronic
      cough due to GERD resistant to intensive medical therapy. There is a clinical
      profile that can predict when GERD is the likely cause of cough. GERD cannot be
      excluded on clinical grounds as the potential cause of cough. The term acid
      reflux disease, when applied to chronic cough due to GERD, can be a misnomer.

PMID- 11948042
TI  - Evaluation of a cough-specific quality-of-life questionnaire.
AB  - STUDY OBJECTIVE: To psychometrically evaluate a cough-specific quality-of-life
      questionnaire (CQLQ) in adults. DESIGN: Prospective evaluation of CQLQ using
      three different cohorts of adult subjects with cough. SETTING: Academic tertiary
      care ambulatory medical facilities. PARTICIPANTS: One hundred fifty-four subjects
      complaining of chronic cough, 30 of acute cough, and 31 smokers with cough.
      INTERVENTIONS: Self-administration of the CQLQ in acute coughers, smokers, and
      chronic coughers before and after therapy. MEASUREMENTS: Psychometric analyses
      including factor analysis (FA), and assessments of reliability and validity.
      RESULTS: Acute and chronic cough data were subjected to FA, and the Cronbach
      alpha and interitem correlations were computed. FA of chronic and acute cough
      data (n = 184) revealed six subscales. The Cronbach alpha for the total CQLQ was
      0.92, and it was 0.62 to 0.86 (mean, 0.76) for the six subscales. Interitem
      correlations for the total CQLQ ranged from -0.06 to 0.72, with a mean of 0.28.
      Test-retest reliability in 52 chronic coughers demonstrated nonsignificant
      changes with readministration of the questionnaire, and the intraclass
      correlation for total CQLQ was 0.89, and for the subscales the range was 0.75 to
      0.93. Analysis of variance followed by tests of contrasts among all possible
      pairings of chronic coughers, acute coughers, and smokers showed significant
      differences (p < or = 0.001) among the groups. Posttreatment cure scores were
      significantly lower (p < or = 0.001) than pretreatment scores in 24 chronic
      coughers. CONCLUSIONS: The 28-item CQLQ has dimensionality that is consistent
      with a cough-specific quality-of-life instrument. It is a valid and reliable
      method by which to assess the impact of cough on the quality of life of chronic
      and acute coughers, and the efficacy of cough therapies in chronic coughers.

PMID- 11948044
TI  - Effects of hypocapnic hyperventilation on the response to hypoxia in normal
      subjects receiving intermittent positive-pressure ventilation.
AB  - OBJECTIVE: To confirm the hypothesis that the ventilatory response to hypoxia
      (VRH) may be abolished by hypocapnia. METHODS: We studied four healthy subjects
      during intermittent positive-pressure ventilation delivered through a nasal mask
      (nIPPV). Delivered minute ventilation (Ed) was progressively increased to lower
      end-tidal carbon dioxide pressure (PETCO(2)) below the apneic threshold. Then, at
      different hypocapnic levels, nitrogen was added to induce falls in oxygen
      saturation, a hypoxic run (N(2) run). For each N(2) run, the reappearance of a
      diaphragmatic muscle activity and/or an increase in effective minute ventilation
      (E) and/or deformations in mask-pressure tracings were considered as a VRH,
      whereas unchanged tracings signified absence of a VRH. For the N(2) runs
      eliciting a VRH, the threshold response to hypoxia (TRh) was defined as the
      transcutaneous oxygen saturation level that corresponds to the beginning of the
      ventilatory changes. RESULTS: Thirty-seven N(2) runs were performed (7 N(2) runs
      during wakefulness and 30 N(2) runs during sleep). For severe hypocapnia
      (PETCO(2) of 27.1 +/- 5.2 mm Hg), no VRH was noted, whereas a VRH was observed
      for N(2) runs performed at significantly higher PETCO(2) levels (PETCO(2) of 34.0
      +/- 2.1 mm Hg, p < 0.001). Deep oxygen desaturation (up to 64%) never elicited a
      VRH when the PETCO(2) level was < 29.3 mm Hg, which was considered the carbon
      dioxide inhibition threshold. For the 16 N(2) runs inducing a VRH, no
      correlations were found between PETCO(2) and TRh and between TRh and both Ed and
      E. CONCLUSION: During nIPPV, VRH is highly dependent on the carbon dioxide level
      and can be definitely abolished for severe hypocapnia.

PMID- 11948045
TI  - Noninvasive positive-pressure ventilation vs. conventional oxygen supplementation
      in hypoxemic patients undergoing diagnostic bronchoscopy.
AB  - OBJECTIVE: We have reported previously on the use of noninvasive positive
      pressure ventilation (NPPV) to assist spontaneous breathing in high-risk
      hypoxemic patients (i.e., PaO(2)/fraction of inspired oxygen [FIO(2)] ratio, < or
      = 100) who are undergoing diagnostic fiberoptic bronchoscopy (FOB). The efficacy
      of this intervention in patients with less severe forms of hypoxemia (i.e.,
      PaO(2)/FIO(2) ratio, < 200) is unknown. PATIENTS AND METHODS: Twenty-six patients
      with PaO(2)/FIO(2) ratios < or = 200 who required bronchoscopic BAL for suspected
      nosocomial pneumonia were entered into the study. Thirteen patients were
      randomized during FOB to receive NPPV, and 13 patients were randomized to receive
      conventional oxygen supplementation by Venturi mask. The primary end points were
      changes in the PaO(2)/FIO(2) ratio during FOB and within 60 min of terminating
      the procedure. RESULTS AND OUTCOME: At study entry, the two groups were similar
      in terms of age, simplified acute physiologic score II values, and
      cardiorespiratory parameters. During FOB, the mean (+/- SD) PaO(2)/FIO(2) ratio
      increased by 82% in the NPPV group (261 +/- 100 vs 139 +/- 38; p < 0.001) and
      decreased by 10% in the conventional oxygen supplementation group (155 +/- 24 to
      139 +/- 38; p = 0.23). Sixty minutes after undergoing FOB, the NPPV group had a
      higher mean PaO(2)/FIO(2) ratio (176 +/- 62 vs 140 +/- 38; p = 0.09), a lower
      mean heart rate (91 +/- 18 vs. 108 +/- 15 beats/min; p = 0.02), and no reduction
      in mean arterial pressure in comparison to a 15% decrease from the baseline in
      the control group. One patient in the NPPV group and two patients in the control
      group required nonemergent intubation. Major bacterial isolates included
      Staphylococcus aureus (7 of 30 isolates; 23%) and Pseudomonas aeruginosa (12 of
      30 isolates; 40%). CONCLUSION: In patients with severe hypoxemia, NPPV is
      superior to conventional oxygen supplementation in preventing gas-exchange
      deterioration during FOB with better hemodynamic tolerance.

PMID- 11948046
TI  - Observation-only management of early stage, medically inoperable lung cancer:
      poor outcome.
AB  - STUDY OBJECTIVES: To assess the treatments received and outcomes of patients with
      early stage non-small cell lung carcinoma (NSCLC). DESIGN: A retrospective study
      of patients identified from the institutional tumor registry between 1994 and
      1999. SETTING: The Richard L. Roudebush VA Medical Center, Indianapolis, IN.
      PATIENTS: All patients with stage I and II NSCLC as identified above.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Of 128 patients identified, 49
      patients received no cancer treatment, 36 patients received radiation therapy
      only, and 43 patients were treated with primary surgery. Median +/- SD survival
      time following surgery was 46.2 +/- 3.15 months; for no treatment, 14.2 +/- 2.37
      months (p = 3.2 x 10(-6)); and radiotherapy alone, 19.9 +/- 5.6 months (p =
      0.0005). Of those who received no specific cancer treatment, 14 patients refused
      treatment and the remainder were not treated for a variety of medical reasons.
      Cause of death was cancer in 53% of untreated patients and 43% for those
      receiving radiotherapy. Radiotherapy was administered for postobstructive
      atelectasis, hemoptysis, increasing tumor size, pain, pleural effusion, and
      medical inoperability. Radiation dosages had no apparent standard. No significant
      differences in survival were found for patients receiving radiotherapy with
      either curative or palliative intent (20.3 months vs 16.0 months, respectively; p
      = 0.229). CONCLUSIONS: Within the limitations of this retrospective study, it
      appears that untreated early stage lung cancer has a poor outcome, with > 50% of
      patients dying of lung cancer. Surgery remains the treatment of choice, but lung
      cancer screening programs will result in increasing numbers of medically
      inoperable patients with no clear policies for their management.

PMID- 11948047
TI  - Management of pneumothorax after percutaneous CT-guided lung biopsy.
AB  - OBJECTIVES: To evaluate the efficacy of simple aspiration of air from the pleural
      space to prevent increased pneumothorax and to avoid chest tube placement in
      cases of pneumothorax following CT-guided lung biopsy. DESIGN: Observational.
      MATERIALS AND METHODS: One hundred thirty-four consecutive percutaneous needle
      lung biopsies using real-time CT fluoroscopy guidance formed the basis of our
      study. All patients that demonstrated moderate or severe pneumothorax on
      postbiopsy chest CT images underwent percutaneous manual aspiration regardless of
      symptoms while on the CT scanner table. Correlation between the incidence of
      pneumothorax after biopsy and many factors (i.e., gender, age, number of pleural
      passes, presence of emphysema, lesion size, and lesion depth) were determined,
      and management of each case of biopsy-induced pneumothorax was reviewed. RESULTS:
      Postbiopsy pneumothorax occurred in 46 of 134 procedures (34.3%). Twenty of the
      46 patients were treated by manual aspiration, while 26 patients were simply
      observed. In 43 of the 46 pneumothoraces (93.5%), the pneumothorax resolved
      completely on follow-up chest radiographs without requiring tube placement. Only
      three patients (2.2% of the entire series; 6.5% of those who had pneumothorax
      develop) required chest tube placement. The risk of pneumothorax significantly
      increased with lesion size and depth. CONCLUSION: Results of our nonprospective,
      nonrandomized study suggest that percutaneous manual aspiration of biopsy-induced
      pneumothorax performed immediately after biopsy may prevent progressive
      pneumothorax and subsequent chest tube placement.

PMID- 11948048
TI  - Mediastinal transthoracic needle and core lymph node biopsy: should it replace
      mediastinoscopy?
AB  - STUDY OBJECTIVES: Primary assessment of mediastinal lymph nodes (N2 or N3) for
      staging lung cancer by transthoracic needle with or without core biopsy.
      Mediastinoscopy only performed after FNA failed to yield a diagnosis. DESIGN AND
      SETTINGS: A retrospective study in a university setting. PATIENTS: Eighty-nine
      patients with mediastinal lymphadenopathy (> 1.5 cm in short-axis diameter) by
      CT. METHODS: Mediastinal transthoracic fine-needle aspiration (FNA) with or
      without core biopsy was performed prior to mediastinoscopy in 89 patients with
      mediastinal lymphadenopathy (lymph node > 1.5 cm in short-axis diameter) or
      masses by CT. RESULTS: Mediastinal transthoracic FNA was used alone in 39 of 89
      patients, or with core biopsy in 50 of 89 patients. Mediastinal transthoracic FNA
      with or without core biopsy was diagnostic in 69 of 89 patients (77.5%) for
      cancer cell type, sarcoidosis, or caseating granulomas with or without
      tuberculosis. Transthoracic FNA with or without core biopsy of nodal stations
      (total, 94 biopsies) judged readily accessible by mediastinoscopy (n = 59)
      included paratracheal (n = 56) and highest mediastinal (n = 3); those more
      difficult (n = 26) included subcarinal (n = 20) and aorticopulmonary window (n =
      6); and those impossible (n = 9) included paraesophageal and pulmonary ligament
      (n = 6), parasternal (n = 2), and para-aortic (n = 1). Innovative lung protective
      techniques for CT-guided biopsy access windows included "iatrogenic-controlled
      pneumothorax" (n = 10) or saline solution injection creating a "salinoma" (n =
      11). Pneumothorax was detected in only 10% with a "protective" technique but 60%
      when traversing lung parenchyma. Transthoracic FNA with or without core biopsy
      failed to yield a diagnosis in 20 of 89 patients (22.5%); all then underwent
      mediastinoscopy, with 11 of 20 procedures (55%) diagnostic for cancer, and 9 of
      20 procedures diagnostic of benign diagnosis or no cancer. CONCLUSION:
      Transthoracic FNA with or without core biopsy accesses virtually all mediastinal
      nodal stations is diagnostic in 78% of cases with mediastinal adenopathy or
      masses, and should precede mediastinoscopy in the staging of lung cancer or
      workup of mediastinal masses.

PMID- 11948049
TI  - Diagnosis of invasive pulmonary aspergillosis using polymerase chain reaction
      based detection of aspergillus in BAL.
AB  - STUDY OBJECTIVE: To assess the value of Aspergillus polymerase chain reaction
      (PCR) test performed on the BAL in diagnosing invasive pulmonary aspergillosis
      (IPA). DESIGN: Between January 1996 and 1997, we prospectively followed up 249
      cancer patients with pulmonary infiltrates suggestive of pneumonia. Bronchoscopy
      with fungal stains, cultures, and PCR was performed on all patients. PCR was used
      for the detection of Aspergillus mitochondrial and alkaline protease gene DNA.
      The PCR products were visualized either directly on polyacrylamide gel or after
      Southern transfer and probing with specific probes for mitochondrial and alkaline
      protease DNA. RESULTS: The 249 patients consisted of 10 patients with proven IPA
      (tissue invasion), 22 patients with probable IPA (microbiologic culture), 18
      patients with possible IPA (consistent clinical and radiologic findings), and 199
      control patients with no evidence of IPA. PCR positivity was strongly associated
      with all forms of IPA (p < 0.002). The sensitivity, specificity, positive
      predictive value, and negative predictive value of PCR were 80%, 93%, 38%, and
      99%, respectively, for proven IPA, and 64%, 93%, 52%, and 96%, respectively, for
      probable IPA. Southern blotting analysis did not improve the diagnostic yield of
      the PCR test. CONCLUSION: PCR performed on BAL is associated with high
      specificity and negative predictive value for IPA. The low positive predictive
      value could be related to the transient colonizing presence of aspergilli in the
      respiratory tract. The sensitivity correlates with the certainty of the diagnosis
      based on tissue invasion.

PMID- 11948050
TI  - Assessment of lymph node tuberculosis in northern Germany: a clinical review.
AB  - AIM OF STUDY: To evaluate patient profiles, diagnostic approaches, and treatment
      strategies in patients with lymph node tuberculosis. METHODS: Demographic data,
      diagnostic findings, and therapies were retrospectively analyzed in 60 patients
      with lymph node tuberculosis who were hospitalized between 1992 and 1999.
      RESULTS: Thirty percent (n = 18) of patients were natives, and 70% were
      immigrants (n = 42). The cervical lymph nodes were most frequently involved
      (63.3%), followed by the mediastinal lymph nodes (26.7%) and the axillary lymph
      nodes (8.3%). All patients (except one patient who was HIV-positive) showed a
      positive response to tuberculin skin testing. Lymph node excision and fine-needle
      aspiration (FNA) were similarly effective in obtaining sufficient material for
      histologic and microbiological analysis. Mycobacterium tuberculosis was
      identified in 43.3% of patients by microbiological testing, and culture methods
      showed the highest sensitivity. Despite standard treatment, the initial
      enlargement of the lymph nodes occurred in 20% of patients and local
      complications occurred in 10%. CONCLUSION: Lymph node tuberculosis is still an
      important issue in developed countries and has to be considered in differential
      diagnosis. The best approach appears to be a combination of skin testing and FNA.
      Negative results in the identification of M tuberculosis do not exclude the
      diagnosis of lymph node tuberculosis.

PMID- 11948051
TI  - Regional ischemic preconditioning enhances myocardial performance in off-pump
      coronary artery bypass grafting.
AB  - OBJECTIVES: We intended to investigate whether ischemic preconditioning (IP)
      enhances myocardial performance in patients who undergo off-pump coronary artery
      bypass grafting (CABG). DESIGN: A controlled, randomized, prospective study.
      SETTING: A university hospital. PATIENTS: Thirty-two patients with left anterior
      descending coronary artery (LAD) or two-vessel heart disease (including LAD) who
      were to undergo off-pump CABG were randomized into an IP group and a control
      group. INTERVENTIONS: IP was induced by occluding the LAD twice for a 2-min
      period followed by 3-min LAD reperfusion before bypass grafting of the first
      coronary vessel. MEASUREMENTS AND RESULTS: Registration included hemodynamic data
      from the peripheral artery and the pulmonary artery, and the measurement of
      cardiac troponin I (CTnI) and creatine kinase isoenzyme MB (CK-MB) values. IP
      resulted in a complete recovery of the mean stroke volume index (SVI) after the
      operation. In the control subjects, the mean SVI showed a significant reduction
      postoperatively (p = 0.039). On the first postoperative day, the increase in the
      mean heart rate (HR) was also significantly lower in the IP patients. The CTnI
      level was statistically significantly lower in the IP group (p = 0.043), and IP
      patients tended to have a smaller CK-MB release after surgery (not significant).
      The duration of mechanical ventilation, the length of stay in the ICU, and the
      use of inotropic medication did not increase after the IP protocol. CONCLUSIONS:
      Two cycles of regional 2-min IP in the LAD, followed by 3 min of reperfusion,
      proved to be applicable and safe in patients undergoing off-pump myocardial
      revascularization, it tended to decrease the immediate myocardial enzyme release,
      it prohibited the postoperative increase in HR, and it enhanced the recovery of
      SVI.

PMID- 11948052
TI  - Off-pump coronary revascularization attenuates transient renal damage compared
      with on-pump coronary revascularization.
AB  - STUDY OBJECTIVES: Cardiopulmonary bypass (CPB) represents a specific risk factor
      for renal damage during coronary revascularization. The purpose of this study was
      to compare the perioperative renal damage in patients undergoing on-pump and off
      pump coronary surgery. DESIGN AND PATIENTS: The progress and extent of renal
      damage was prospectively studied in two groups of patients undergoing cardiac
      surgery without concomitant morbidity, undergoing elective coronary
      revascularization with (n = 12) and without (n = 10) CPB. Markers of glomerular
      function (creatinine clearance) and damage (microalbuminuria), and markers of
      tubular function (fractional excretion of sodium [FENa] and free water clearance)
      and damage (N-acetyl-beta-D glucosaminidase [NAG]) were evaluated. Measuring
      plasma concentrations of free hemoglobin assessed hemolysis. Plasma and urinary
      specimens were obtained at the following points: (1) baseline; (2)
      heparinization; (3) the end of CPB or completing graft for off-pump surgery; (4)
      skin closure; (5) the sixth hour in the ICU; and (6) the second postoperative
      day. Free water and creatinine clearances, FENa, and the urinary excretion of
      microalbumin and NAG were calculated for the corresponding time intervals.
      SETTING: University hospital. RESULTS: We found that off-pump coronary
      revascularization induced significantly less changes in microalbuminuria, FENa,
      free water clearance, NAG, and free hemoglobin as compared with operations with
      CPB. Markers returned to baseline within 2 days after the operation, and there
      was no clinical or laboratory evidence of overt renal dysfunction in both groups.
      CONCLUSION: Off-pump coronary surgery attenuates transient renal injury compared
      with traditional on-pump coronary artery bypass grafting.

PMID- 11948053
TI  - Relationship between interleukin-6 production in the lungs and pulmonary vascular
      resistance in patients with congestive heart failure.
AB  - STUDY OBJECTIVES: We evaluated whether interleukin (IL)-6 is produced in the
      pulmonary circulation and investigated the relationship between IL-6 spillover in
      the lung and pulmonary vascular resistance (PVR) in patients with congestive
      heart failure (CHF). PATIENTS AND INTERVENTIONS: Blood samples were obtained from
      the main pulmonary artery and pulmonary capillary wedge region in 50 patients
      with symptomatic left ventricular dysfunction, who had undergone cardiac
      catheterization, and 9 age-matched control subjects. Plasma IL-6, tumor necrosis
      factor-alpha, norepinephrine (NE), endothelin-1, atrial and brain natriuretic
      peptide, and cyclic guanosine monophosphate (cGMP) levels were determined.
      MEASUREMENTS AND RESULTS: Plasma IL-6 concentrations were significantly higher in
      the pulmonary capillary wedge region than in the main pulmonary artery in both
      control subjects and patients with CHF. IL-6 production in the lung increased
      markedly in patients with severe CHF compared with control subjects and patients
      with mild CHF. Among hemodynamic variables, neurohumoral factors, and
      medications, plasma NE levels (p < 0.0001) showed an independent and significant
      positive relationship with IL-6 production in the lung, and treatment with beta
      blockers (p = 0.004) showed an independent and significant negative relationship
      with IL-6 production in the lung. There was a significant positive correlation
      between IL-6 production in the lung and both PVR (r = 0.43; p = 0.001) and cGMP
      production in the lung (r = 0.498; p < 0.0001). CONCLUSION: IL-6 production in
      the pulmonary circulation increases with the severity of CHF and is mainly
      associated with the activation of the sympathetic nervous system. The local
      production of IL-6 in the lung may modify PVR in patients with CHF.

PMID- 11948054
TI  - Amiodarone vs. sotalol as prophylaxis against atrial fibrillation/flutter after
      heart surgery: a meta-analysis.
AB  - BACKGROUND: The incidence of supraventricular arrhythmias remains high following
      open-heart surgery. The most common of these arrhythmias are atrial fibrillation
      and flutter (AFF), for which treatment is not well defined. Recent studies have
      focused on prophylactically treating patients in an attempt to reduce
      postoperative AFF. Several studies have shown that sotalol and amiodarone are
      both effective in reducing AFF following heart surgery. However, no studies have
      been done comparing both drugs. METHODS: A meta-analysis was done to compare the
      efficacy of sotalol and amiodarone after bypass graft surgery. Randomized
      controlled trials were included if patients were clearly monitored, and the
      incidence of AFF was noted. Ten studies were included in the final analysis.
      RESULTS: Both amiodarone and sotalol were more effective than placebo treatment
      in reducing the incidence of postoperative AFF. However, when the data were
      pooled, no differences were noted between amiodarone and sotalol for efficacy
      (sotalol, - 21.5%; 95% confidence interval [CI], - 28.3 to - 14.6; amiodarone, -
      14.1%; CI, - 20.1 to - 8.1), length of stay (sotalol, - 0.13 d; CI, - 0.33 to
      0.07 d; amiodarone, - 0.18; CI, - 0.38 to 0.02 d), or adverse drug reactions
      causing drug termination (sotalol, 9.7%; CI, 0.086 to 19.3; amiodarone, 1.95%;
      CI, - 0.48 to 4.38). CONCLUSIONS: This data would suggest that either drug could
      be used in a prophylactic regimen to reduce the incidence of AFF following heart
      surgery.

PMID- 11948056
TI  - Prognostic value of low-dose dobutamine echocardiography in patients with
      idiopathic dilated cardiomyopathy.
AB  - STUDY OBJECTIVES: Dobutamine echocardiography is widely used for the evaluation
      of myocardial contractile reserve. The purpose of the study was to determine the
      prognostic value of low-dose dobutamine echocardiography in patients with
      idiopathic dilated cardiomyopathy (IDCM). PATIENTS: The study group consisted of
      77 consecutive patients with recently diagnosed IDCM (mean [+/- SD] age, 49 +/- 9
      years; men, 82%) and left ventricular (LV) ejection fractions of < 40%.
      INTERVENTIONS: Two-dimensional and Doppler echocardiographic variables were
      measured before and after the infusion of dobutamine at the rate of 10
      microg/kg/min for 5 min. MEASUREMENTS AND RESULTS: During a mean follow-up period
      of 63 +/- 7 months (range, 49 to 75 months) 30 patients (39%) died and five
      patients (6%) underwent successful heart transplantations. Using multivariate
      regression analysis, the only significant factors related to fatal outcome or the
      need for cardiac transplantation were the following: (1) LV end-systolic volume
      of > 150 mL after low-dose dobutamine infusion (odds ratio [OR], 2.2; confidence
      interval [CI], 1.2 to 4.1; p = 0.011); (2) no decrease of LV end-diastolic volume
      after dobutamine infusion (OR, 1.9; CI, 1.1 to 3.4; p = 0.031); (3) atrial
      fibrillation (OR, 2.7; CI, 1.4 to 5.3; p = 0.003); and (4) male gender (OR, 2.6;
      CI, 1.2 to 5.5; p = 0.017). A scoring system was proposed with one point assigned
      for each of the above-mentioned factors. The mortality rates for total scores of
      0, 1, 2, 3, and 4 were 0%, 19%, 48%, 83%, and 100%, respectively. CONCLUSION: The
      response of the LV to low-dose dobutamine infusion adds clinically valuable
      prognostic information to the evaluation of the patient with IDCM.

PMID- 11948055
TI  - Hyperlipidemia prevents the expected reduction of myocardial ischemia on repeated
      balloon inflations during angioplasty.
AB  - BACKGROUND: Controversy exists regarding inhibition of ischemic preconditioning
      in hyperlipidemic animals. In this study, we tested the hypothesis that
      hyperlipidemia inhibits the normal reduction of myocardial ischemia on repeated
      balloon inflations (BIs) during angioplasty. METHODS: We studied 33 patients
      undergoing coronary angioplasty. All underwent a minimum of three BIs. Patients
      were grouped according to the following plasma cholesterol levels: 13 patients
      had total cholesterol levels < 200 mg/dL (the normal cholesterol group); and 20
      patients had total cholesterol levels > or = 200 mg/dL (the elevated cholesterol
      group). Surface ST-segment elevations were recorded at the end of each BI.
      RESULTS: In the normal cholesterol group, the mean (+/- SD) ST-segment elevation
      decreased from 0.21 +/- 0.15 mV during the first BI to 0.11 +/- 0.11 mV during
      the third BI (p < 0.05). In the elevated cholesterol group, the respective
      decrease was from 0.18 +/- 0.16 to 0.14 +/- 0.15 mV (p = not significant)
      [between-group comparisons: F = 3.97; p = 0.02]. The decrease in ST-segment
      elevation was correlated with the total cholesterol levels (r = -0.48; p =
      0.005), the low-density lipoprotein (LDL) cholesterol levels (r = -0.50; p =
      0.003), and the high-density lipoprotein/LDL levels (r = 0.44; p = 0.01).
      CONCLUSION: Hyperlipidemia prevents the normal reduction of myocardial ischemia
      on repeated BIs during angioplasty. This leads to the clinical implication that
      reduction of cholesterol plasma levels, apart from its other known benefits,
      could also have a beneficial effect on cardioprotection.

PMID- 11948057
TI  - Bronchial hyperreactivity in patients who inhale heroin mixed with cocaine
      vaporized on aluminum foil.
AB  - BACKGROUND: In our area, inhaling heroin mixed with cocaine vaporized on aluminum
      foil, known as rebujo, is becoming more and more common. AIM: To define the
      prevalence and the characteristics of bronchial disease (wheezing, bronchial
      hyperreactivity [BHR], and asthma) present in subjects inhaling heroin mixed with
      cocaine vaporized on aluminum foil. MATERIALS AND METHODS: Ninety-one subjects
      who inhaled the drug mixture were included in the study: 62 subjects were from a
      drug rehabilitation center (INH-I group), and 29 subjects were among patients
      admitted to our hospital for a variety of reasons (INH-II group). A questionnaire
      was completed in both groups, as well as IgE determination and lung function
      tests (spirometry and methacholine challenge). The control group consisted of 122
      individuals who did not inhale the drug mixture, and were chosen randomly from
      the general population (NO-INH group). All subjects were tobacco smokers.
      RESULTS: In the INH-I group, there was a 41.9% prevalence of wheezing over the
      past 12 months, a 44.4% prevalence of BHR, and a 22.02% prevalence of asthma,
      defined as wheezing plus BHR. In the NO-INH group, these values were 32.78% (p =
      0.22), 15.57% (p < 0.0001), and 8.19% (p < 0.01), respectively. Of the subjects
      who inhaled the drug mixture and denied having symptoms prior to the use of the
      drug mixture, 31.4% had wheezing develop after commencing use of the drug,
      following a mean latency of 4.09 months. Wheezing remitted in only 7.6% after
      discontinuation of the drug. CONCLUSIONS: (1) There is a real increase in BHR in
      subjects who inhale heroin mixed with cocaine vaporized on aluminum foil; and (2)
      this BHR is associated with wheezing that develops after a variable period of
      latency, once drug inhalation begins, and persists despite discontinuation of the
      drug.

PMID- 11948058
TI  - Evidence of chronic damage to the pulmonary microcirculation in habitual users of
      alkaloidal ("crack") cocaine.
AB  - STUDY OBJECTIVE: To evaluate BAL cells obtained from habitual users of alkaloidal
      ("crack") cocaine alone or in combination with tobacco, for evidence of cocaine
      associated alveolar injury. DESIGN: Prospective cohort study. PATIENTS: A total
      of 36 healthy men and women (mean age [SD], 37.5 [7.5] years), including 10
      cocaine-only smokers (CS), 6 cocaine-plus-tobacco smokers (CTS), 10 tobacco
      smokers (TS), and 10 nonsmokers (NS), underwent fiberoptic bronchoscopy and BAL.
      METHODS: Cytospins were prepared from BAL cells and stained with Wright-Giemsa
      for cell differentials and Gomori's stain for detection of hemosiderin.
      Endothelin (ET)-1 levels were determined from lavage fluid by enzyme-linked
      immunosorbent assay. RESULTS: None of the cocaine users reported episodes of
      hemoptysis or respiratory distress, and routine spirometry findings were within
      normal limits in all subjects. While there was little effect on total cell
      numbers or differential counts, the percentages of hemosiderin-positive alveolar
      macrophages (AMs) were markedly increased in CS (33.8 +/- 8.7% [SEM]) compared to
      TS and NS (< 2%; p < 0.05). The percentages of hemosiderin-laden AMs were also
      numerically increased in CTS (11.8 +/- 7.8%), but this value was not
      statistically significant from that of TS or NS. ET-1 levels were significantly
      increased in the fluid recovered from CS (6.2 +/- 0.8 pg/mL) when compared to NS
      (1.2 +/- 0.4 pg/mL) and TS (1.3 +/- 0.2 pg/mL) [p < 0.05], while ET-1 levels were
      elevated to a lesser extent in CTS (2.5 +/- 0.6 pg/mL). ET-1 levels correlated
      with the percentage of hemosiderin-positive AMs when CS were analyzed in
      conjunction with CTS (r = 0.64; p = 0.0004). CONCLUSION: Clinically inapparent
      alveolar hemorrhage occurs frequently in otherwise healthy crack cocaine smokers
      and is associated with elevated levels of ET-1, indicative of cocaine-induced
      pulmonary microvascular injury.

PMID- 11948059
TI  - Delayed cutaneous hypersensitivity tests and lymphopenia as activity markers in
      sarcoidosis.
AB  - STUDY OBJECTIVES: To evaluate new and already known biological markers of
      activity in patients with sarcoidosis. DESIGN: A 10-year prospective clinical
      evaluation, including a battery of delayed cutaneous hypersensitivity tests
      (DCHTs) and other markers of activity. SETTING: Outpatient department of a
      university teaching hospital. PATIENTS: Forty patients with biopsy-proven
      sarcoidosis were prospectively evaluated every 6 months. In this study, only the
      visits that fulfilled the situation of active period (AcP) or of asymptomatic
      period (AsP) were taken into account. Twenty-one visits were considered to be in
      the AcP, and 26 were considered to be in the AsP. Seven patients were studied
      both in the AcP and the AsP. INTERVENTIONS: DCHTs and blood sample extraction
      every 6 months. MEASUREMENTS AND RESULTS: The mean diameter of the cutaneous
      wheal for each antigen (AG) was lower in the AcP group than in the AsP group
      (candidine, p < 0.0001; tuberculin, p < 0.0009; trichophytin, p < 0.02;
      streptokinase-streptodornase, p < 0.001). Also, the mean (+/- SD) diameter for
      the four AGs taken together was lower in the AcP group (2.3 +/- 4.2 mm) than in
      the AsP group (16.8 +/- 9.3 mm; p < 0.0001). The mean serum angiotensin
      converting enzyme (S-ACE) value was higher in the AcP group than in the AsP group
      (p < 0.02). A low lymphocyte count and a percentage of the lymphocyte count (<
      20%) also were detected more frequently in the AcP group than in the AsP group (p
      < 0.02 and p < 0.0001, respectively). CONCLUSIONS: DCHTs appear to be a simple,
      reliable, and easily performed marker of inflammatory activity in sarcoidosis
      patients. Furthermore, serum total and differential lymphocyte count and the S
      ACE level proved to be useful inflammatory markers in this study.

PMID- 11948060
TI  - Changes in BP induced by passive leg raising predict response to fluid loading in
      critically ill patients.
AB  - OBJECTIVE: To test the hypothesis that passive leg raising (PLR) induces changes
      in arterial pulse pressure that can help to predict the response to rapid fluid
      loading (RFL) in patients with acute circulatory failure who are receiving
      mechanical ventilation. DESIGN: Prospective clinical study. SETTING: Two medical
      ICUs in university hospitals. PATIENTS: Thirty-nine patients with acute
      circulatory failure who were receiving mechanical ventilation and had a pulmonary
      artery catheter in place. INTERVENTIONS: PLR for > 4 min and a subsequent 300-mL
      RFL for > 20 min. MEASUREMENTS AND MAIN RESULTS: Radial artery pulse pressure
      (PPrad), heart rate, right atrial pressure, pulmonary artery occlusion pressure
      (PAOP), and cardiac output were measured invasively in a population of 15
      patients at each phase of the study procedure (i.e., before and during PLR, and
      then before and after RFL). PPrad, PAOP, and stroke volume (SV) significantly
      increased in patients performing PLR. These changes were rapidly reversible when
      the patients' legs were lowered. Changes in PPrad during PLR were significantly
      correlated with changes in SV during PLR (r = 0.77; p < 0.001). Changes in SV
      induced by PLR and by RFL were significantly correlated (r = 0.89; p < 0.001).
      Finally, PLR-induced changes in PPrad were significantly correlated to RFL
      induced changes in SV (r = 0.84; p < 0.001). In a second population of 24
      patients, we found the same relationship between PLR-induced changes in PPrad and
      RFL-induced changes in SV (r = 0.73; p < 0.001). CONCLUSION: The response to RFL
      could be predicted noninvasively by a simple observation of changes in pulse
      pressure during PLR in patients with acute circulatory failure who were receiving
      mechanical ventilation.

PMID- 11948061
TI  - A multicenter description of intermediate-care patients: comparison with ICU low
      risk monitor patients.
AB  - STUDY OBJECTIVES: To describe the characteristics and outcomes of patients
      admitted to intermediate-care areas (ICAs) and to compare them with those of ICU
      patients who receive monitoring only on day 1 and are at a low risk (i.e., < 10%)
      for receiving subsequent active life-supporting therapy (i.e., low-risk monitor
      patients). DESIGN: Nonrandomized, retrospective, cohort study. SETTING: Thirteen
      US teaching hospitals and 19 nonteaching hospitals. PATIENTS: A consecutive
      sample of 8,971 patients at 37 ICAs and 5,116 low-risk (i.e., < 10%) monitor
      patients at 59 ICUs in 32 US hospitals. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: We recorded demographic and clinical characteristics, resource use, and
      outcomes for the ICA and ICU low-risk monitor patients. Patient data and outcomes
      for this study were collected concurrently or retrospectively. ICA and ICU low
      risk monitor patients were similar in regard to gender, race, and frequency of
      comorbitities, but ICA patients were significantly (p < 0.001) older, had fewer
      physiologic abnormalities (mean acute physiology score, 16.7 vs 19.8,
      respectively), and were more frequently admitted due to nonoperative diagnoses.
      The mean length of stay for ICA patients was significantly longer (3.9 days) than
      for ICU low-risk monitor patients (2.6 days; p < 0.001). The hospital mortality
      rate was significantly higher for ICA patients (3.1%) compared to ICU low-risk
      monitor patients (2.3%; p = 0.002). CONCLUSIONS: The clinical features of ICA
      patients are similar, but not identical to, those of less severely ill ICU
      monitor patients. Comparisons of hospital death rates and lengths of stay for
      these patients should be adjusted for characteristics that previously have been
      shown to influence these outcomes.

PMID- 11948062
TI  - D-dimer correlates with proinflammatory cytokine levels and outcomes in
      critically ill patients.
AB  - STUDY OBJECTIVES: To determine the relationship between d-dimer (DD) and both
      proinflammatory and anti-inflammatory cytokine levels, and to confirm the
      association between DD status and outcomes in critically ill patients. DESIGN:
      Prospective observational study. SETTING: Medical ICU (MICU) of a tertiary care,
      academic medical center. PATIENTS: Individuals admitted to the MICU.
      INTERVENTIONS: Within 24 h of MICU admission, patients had DD status determined
      and interleukin (IL) levels (IL-6, IL-8, and IL-10) and tumor necrosis factor
      (TNF)-alpha measured. The strength of the DD level was also noted. Subjects were
      then monitored prospectively to determine mortality rate and the incidence of
      organ failure. MEASUREMENT AND RESULTS: The study cohort included 79 patients
      (mean age, 65.2 years; 54.5% male patients). DD was present in 53.2% of subjects.
      The DD reaction was weak (1+) in 15 patients and strong (2+) in 27 patients. The
      TNF-alpha, IL-6, and IL-8 levels all increased in parallel with the increasing
      strength of the DD level. IL-10 levels did not differ based on DD status.
      Similarly, the severity of illness as measured by the APACHE (acute physiology
      and chronic health evaluation) II score was highest among those with higher DD
      levels: 24.7 +/- 6.2 for those with 2+ DD vs 17.2 +/- 3.1 and 11.5 +/- 2.7 for
      those with 1+ DD and no circulating DD, respectively (p < 0.001). For patients
      lacking DD, the mortality rate was 8.1%, compared to 13.3% and 55.6% for those
      with 1+ and 2+ DD levels, respectively (p < 0.001). No patient without DD had
      multisystem organ failure (MSOF) develop, while the incidence of MSOF also
      increased with increasing DD levels. As a screening test for mortality, the DD
      performed as well as the APACHE II system. CONCLUSIONS: The coagulation system is
      active in critically ill patients, and DD levels correlate with activation of the
      proinflammatory cytokine cascade. The absence of a relationship between DD and
      anti-inflammatory cytokines (IL-10) suggests that the presence of DD may reflect
      the imbalance between proinflammatory and anti-inflammatory cytokines. DD
      identifies patients at increased risk for both MSOF and death.

PMID- 11948063
TI  - Pulmonary dysfunction after cardiac surgery.
AB  - Postoperative lung injury is one of the most frequent complications of cardiac
      surgery that impacts significantly on health-care expenditures and largely has
      been believed to result from the use of cardiopulmonary bypass (CPB). However,
      recent comparative studies between conventional and off-pump coronary artery
      bypass grafting have indicated that CPB itself may not be the major contributor
      to the development of postoperative pulmonary dysfunction. In our study, we
      review the associated physiologic, biochemical, and histologic changes, with
      particular reference to the current understanding of underlying mechanisms.
      Intraoperative modifications aiming at limiting lung injury are discussed. The
      potential benefits of maintaining ventilation and pulmonary artery perfusion
      during CPB warrant further investigation.

PMID- 11948064
TI  - Association of malignancy with diseases causing interstitial pulmonary changes.
AB  - A number of studies have shown a high incidence of lung cancer in patients with
      idiopathic pulmonary fibrosis (9.8 to 38%) compared to control subjects (2 to
      6.4%). A similar trend occurs in other entities that affect the interstitial lung
      compartment, such as systemic sclerosis and sarcoidosis, as well as occupational
      diseases. The pathogenesis of lung cancer in patients with diffuse pulmonary
      fibrosis is still unclear. Recent progress in molecular and cellular biology has
      shed some light on the possible interactions of several types of inflammatory
      cells, following the deleterious effects of toxic factors leading to alveolitis,
      and destruction and disorganization of lung parenchyma, which results in
      fibrosis. Further research in the field would enhance our understanding of the
      pathogenic mechanisms of cancer development in these patients, and to explain the
      reason for the different incidence of lung cancer in patients with various
      interstitial lung diseases.

PMID- 11948065
TI  - The design of randomized clinical trials in critically ill patients.
AB  - There are a number of difficulties in the conduct of randomized trials in the
      critically ill. These include difficulties in the definition of diseases and
      syndromes, a heterogenous population of patients undergoing a variety of
      therapeutic interventions, and outcomes that may not be able to discriminate
      between beneficial and risky therapies. Following a brief description of
      different randomized clinical trials (RCTs) and design philosophies, we outline
      the effects of different design choices in the complex critical care environment.
      Once the study topic has been determined to be relevant and important, then the
      potential investigator must establish whether efficacy or effectiveness will be
      the focus of the RCT. If an effectiveness design philosophy is chosen, then broad
      representation of study sites, liberal eligibility criteria, easily implemented
      intervention study protocols, and patient-centered outcomes should be chosen. The
      potential investigator wishing to establish efficacy will conduct the study in
      the centers of excellence and adopt stringent eligibility criteria, rigorous
      study protocols, and opt for outcomes that will be sensitive to change. In
      conclusion, we describe some of the major challenges and possible solutions to
      help a potential investigator through the myriad of difficulties in initiating an
      RCT in a complex environment.

PMID- 11948066
TI  - An evaluation of the quality and contents of asthma education on the World Wide
      Web.
AB  - STUDY OBJECTIVES: To measure the accessibility and quality of currently available
      asthma education World Wide Web sites using the following criteria: accessibility
      by readability, language, and download time; information quality based on
      inclusion of core educational concepts and compliance with Health On the Net
      (HON) principles; and utilization of innovative technology. DESIGN: Objective
      evaluation of 145 Web sites. MEASUREMENTS AND RESULTS: Four search engines or
      directories (Yahoo, HON, Alta Vista, and Healthfinder) were searched for "asthma,
      patient information." A maximum of 50 Web sites from each search engine or
      directory was evaluated. Only 90 of the 145 Web sites actually contained asthma
      educational material. The mean (+/- SD) time necessary to open each Web site on a
      28.800-bits-per-second modem was 33.6 ( +/- 36.6) s. The mean number of graphics
      on the Web sites was 24.6 ( +/- 30.2) files per page. The educational material
      required a mean reading level beyond the 10th grade. Only nine Web sites
      contained multilingual asthma education material. The mean number of HON
      principles with which the Web sites conformed was 6.3 ( +/- 1.0) of 8 principles;
      14 Web sites conformed to all the HON criteria. The average Web site contained
      4.9 (+/- 2.5) of 8 core asthma educational concepts, and only 20 Web sites
      contained all 8 educational concepts. Very few Web sites utilized innovative
      educational technology. CONCLUSIONS: While patient asthma education Web sites are
      common, asthma educational material contains many accessibility barriers, is
      highly variable in quality and content, and takes little innovative use of
      technology. Patient educational material currently available on the World Wide
      Web fails to meet the information needs of patients.

PMID- 11948067
TI  - The increase in allergic respiratory diseases: survival of the fittest?
AB  - The prevalence of allergic respiratory diseases, asthma and allergic
      rhinoconjunctivitis, has increased since the advent of industrialization. The
      inverse relationship between the number of infections early in life and atopy has
      been interpreted as the "hygiene hypothesis." That is, many infections early in
      life promote the development of T helper type 1 cytokines, while fewer infections
      early in life favor the development of T helper type 2 (Th2) cytokines and atopy.
      An alternate interpretation of the same data, that atopy is protective against
      infections early in life, is rarely considered. With epidemiologic, historical,
      and immunologic data, I suggest that human evolution has favored individuals with
      an atopic predisposition. Th2 immune responses promote parity, and ensure
      successful pregnancy and term birth; provide the infant protection against
      infections and the inflammation induced by common pathogens in the first years of
      life until the immune system matures; and protect young adults exposed to viral
      respiratory pathogens. These traits are of particular value with the advent of
      industrialization, especially so in the era prior to the development of
      antibiotics. This theory contradicts the assumption that there is no biological
      or evolutionary advantage for allergic disease to exist in humans and has
      significant implications for our current and future treatments of allergic
      diseases.

PMID- 11948068
TI  - Effect of respiratory protective devices on development of antibody and
      occupational asthma to an acid anhydride.
AB  - STUDY OBJECTIVES: To determine whether the use of respiratory protective
      equipment would reduce the incidence of occupational asthma due to exposure to
      hexahydrophthalic anhydride (HHPA). DESIGN: Prospective cohort study. SETTING: A
      facility that makes an epoxy resin product requiring HHPA for its manufacture.
      PARTICIPANTS: Sixty-six individuals newly hired at a facility that makes an epoxy
      resin product requiring HHPA for its manufacture. INTERVENTION: Employees who
      wished to use respiratory protective equipment could choose from three types of
      masks: dust mask, half-face organic vapor respirator, or full-face organic vapor
      respirator. MEASUREMENTS: Workers were evaluated annually for development of
      positive antibody to HHPA and occupational, immunologic respiratory disease,
      including occupational asthma. RESULTS: With use of respiratory protective
      equipment, the rate of developing an occupational immunologic respiratory disease
      was reduced from approximately 10 to 2% per year. Occupational asthma developed
      in only three individuals, and they were all in the higher exposure category.
      Statistically, one respirator was not superior to the others. CONCLUSION:
      Respiratory protective equipment can reduce the incidence of occupational
      immunologic respiratory disease, including occupational asthma, in employees
      exposed to HHPA.

PMID- 11948069
TI  - Use of specific inhalation challenge in the evaluation of workers at risk for
      occupational asthma: a survey of pulmonary, allergy, and occupational medicine
      residency training programs in the United States and Canada.
AB  - STUDY OBJECTIVES: To document the current practice of occupational asthma (OA)
      diagnosis and use of specific inhalation challenge (SIC). DESIGN, SETTING, AND
      PARTICIPANTS: A survey evaluating the current practice of SIC was mailed to 259
      residency training programs in adult pulmonary diseases, allergy and immunology,
      and occupational medicine accredited in the United States and Canada during the
      year 2000. RESULTS: Forty-six percent (123 of 259 programs) participated. Ninety
      two programs reported that patients with OA were seen during the previous year,
      15 programs reported that SIC had been performed, and 10 programs reported that
      patients had been referred to other sites for SIC. A total of 259 patients
      underwent SIC. No unexpected adverse reactions were reported. Forty-one programs
      reported that they had been willing to undertake SIC but were unable to do so.
      The most common barriers cited were lack of availability of SIC within the
      evaluating institution, inability to locate a site for referral, concerns about
      reimbursement, and lack of an appropriate diagnostic reagent for use in SIC.
      Seventy-four programs indicated that SIC was useful, and 34 programs included
      training in the use of SIC was part of the residency curriculum. CONCLUSION:
      Although SIC is considered the "gold standard" for objective documentation of OA,
      the test is performed in only a few institutions in the United States and Canada.
      Many institutions indicate that SIC is not available, even when desired for
      patient management. Only a minority of participating residency training programs
      include SIC as a formal part of the training curriculum.

PMID- 11948070
TI  - Cardiac inflammation and innate immunity in septic shock: is there a role for
      toll-like receptors?
AB  - Our current understanding of the pathogenesis of sepsis suggests that bacteria as
      well as bacterial-derived products activate an uncontrolled network of host
      derived mediators such as proinflammatory cytokines (ie, tumor necrosis factor
      [TNF] and interleukin [IL]-1beta), which can ultimately lead to cardiovascular
      collapse and death. Despite the potentially important role that TNF and IL-1beta
      may play in producing cardiac dysfunction in human septic shock, little is known
      with regard to the basic biochemical mechanism(s) by which bacterial pathogens
      induce their expression in the heart. A major advance in understanding the early
      events that are downstream from bacterial-mediated signaling has been the
      identification of Toll-like receptors (TLRs). TLR-mediated signaling is known to
      activate the transcription factor nuclear factor-kappaB and to upregulate TNF
      expression. It has recently been shown that the heart expresses TLRs, raising the
      possibility that these receptors may be responsible for mediating the deleterious
      effects of bacterial pathogens on cardiac function. In this review, we will
      discuss the emerging role for TLRs in the pathogenesis of the cardiovascular
      collapse that occurs during sepsis.

PMID- 11948071
TI  - Ethical assessment of industry-sponsored clinical trials: a case analysis.
AB  - The rapid growth of clinical trials sponsored by the pharmaceutical industry and
      conducted by community physicians raises concerns about the scientific quality of
      this research and the adequacy of protections for research participants. In this
      article, we present an in-depth ethical analysis of a recent industry-sponsored
      placebo-controlled study for treatment of asthma. The ethical analysis uses a
      proposed ethical framework for evaluating clinical research focusing on seven
      ethical requirements: (1) scientific value, (2) scientific validity, (3) fair
      subject selection, (4) favorable risk/benefit ratio, (5) independent review, (6)
      informed consent, and (7) respect for enrolled subjects.

PMID- 11948072
TI  - Unilateral air bronchogram in a patient with cystic fibrosis.

PMID- 11948074
TI  - Management of acute hypoxemia during flexible bronchoscopy with insertion of a
      nasopharyngeal tube in lung transplant recipients.
AB  - STUDY OBJECTIVES: To assess the utility of nasopharyngeal tube insertion in the
      management of hypoxemia during flexible bronchoscopy (FB) in lung transplant
      recipients, and to determine the incidence and risk factors of upper-airway
      obstruction (UAO) leading to significant hypoxemia during FB. SETTING: Heart-lung
      transplant unit of a university hospital. PATIENTS AND METHODS: Ninety-six lung
      transplant recipients (47 men and 49 women; mean +/- SD age, 41.4 +/- 13.1 years)
      underwent 714 FB procedures from January 1997 to May 2000. INTERVENTION: A fall
      in oxygen saturation (< or = 90%) in patients receiving 6 L/min of oxygen via
      nasal prongs was treated with insertion of a nasopharyngeal tube, continued
      oxygen supplementation, and withdrawal of the bronchoscope to the trachea. If
      oxygen desaturation persisted at < 90% despite additional oxygen administration
      via a 7F catheter placed either just above the larynx or in the proximal trachea,
      the bronchoscope was withdrawn, reversal of sedation was administered, and bag
      and mask ventilation was instituted until satisfactory spontaneous ventilation
      was achieved. RESULTS: Forty-six patients (47.9%) were treated with
      nasopharyngeal tube insertion on 102 occasions at a mean duration of 168 +/- 178
      days after lung transplantation. In 90 of 102 procedures (88.2%), significant
      hypoxemia due to UAO was successfully treated with nasopharyngeal tube insertion.
      The mean oxygen saturation after nasopharyngeal tube insertion was 97 +/- 3%.
      Male gender, increase in body mass index after lung transplantation, and presence
      of obstructive sleep apnea were significant factors associated with the need for
      nasopharyngeal tube insertion during FB in lung transplant recipients.
      CONCLUSIONS: Significant oxygen desaturation during FB in lung transplant
      recipients is mainly due to UAO. Insertion of a nasopharyngeal tube is a novel
      and a highly effective approach to the management of acute hypoxemia during FB.

PMID- 11948073
TI  - A 39-year-old man with hip pain and respiratory failure.

PMID- 11948075
TI  - Syndrome of iron pill aspiration.
AB  - Bronchial stenosis (BS) consequent to iron pill aspiration (IPA) has been
      observed in few reported cases. This condition is often irreversible and may
      necessitate lobectomy in severe cases. Unlike most foreign bodies (FBs), the iron
      pill disintegrates in the airway and cannot be detected on bronchoscopy. However,
      bronchial biopsy and lung tissue may reveal iron deposits along with airway
      inflammation months after the aspiration. Thus, IPA can be diagnosed by a triad
      of aspiration, airway inflammation, and iron deposits on histology even in the
      absence of an FB. We report a case of IPA with BS in which the diagnosis was
      established by bronchial biopsy and was successfully managed with balloon
      bronchoplasty and therapy with topical mitomycin C.

PMID- 11948076
TI  - Retroperitoneal bronchogenic cyst: a case report.
AB  - A 46-year-old woman presented with a 1-year history of progressive left-arm
      numbness. A cyst below the left hemidiaphragm was discovered incidentally when a
      CT scan was performed to examine the thymus for a suspected tumor. A thymic mass
      was found. MRI indicated that the cyst contained proteinaceous fluid. The thymoma
      was approached through a median sternotomy and resected, but the cyst was found
      to be infradiaphragmatic. A separate, left paraspinal incision was made to access
      the retroperitoneum, and the cyst was resected. Histologic examination showed
      that the cyst was bronchogenic in origin. Retroperitoneal bronchogenic cysts are
      very rare, and only four cases have been reported in the English-language
      literature.

PMID- 11948077
TI  - Malignant ameloblastoma metastatic to the lungs 29 years after primary resection:
      a case report.
AB  - We describe a case of a 55-year-old man presenting with a metastatic malignant
      ameloblastoma 29 years after the primary tumor was resected. This represents the
      longest period between initial diagnosis and first subsequent metastasis recorded
      as a case report. This case illustrates distinctions between the terms metastatic
      and malignant; it also highlights the difficulties derived from the accumulation
      of data by new diagnostic modalities (electron beam CT and positron emission
      tomography) and their integration into assessment algorithms.

PMID- 11948078
TI  - Venous dilatation seen on routine mammography: a clue to superior vena cava
      obstruction.
AB  - A diagnosis of superior vena cava obstruction (SVCO) generally is made on
      clinical grounds and can be confirmed by SVCO-specific diagnostic tests. When the
      obstruction is long-standing, clinical recognition may be compromised as venous
      drainage of the head, neck, chest, and upper extremity is diverted via collateral
      venous channels that bypass the obstructed superior vena cava. In such
      situations, only the visualization of this collateral flow will suggest the
      presence of SVCO. We describe a patient in whom the unanticipated diagnosis of
      SVCO was first suggested when routine mammography revealed grossly dilated
      superficial veins of both breasts, which were the result of collateral flow.

PMID- 11948079
TI  - Pamidronate results in symptom control of hypertrophic pulmonary osteoarthropathy
      in cystic fibrosis.
AB  - Hypertrophic pulmonary osteoarthropathy (HPOA) may complicate the advanced lung
      disease that is associated with cystic fibrosis, resulting in severe joint pain
      and early-morning stiffness. Symptoms are usually controlled with the
      administration of nonsteroidal anti-inflammatory drugs, physiotherapy, and, on
      occasions, oral corticosteroids. This report describes a case of refractory HPOA
      with complete remission following the administration of IV pamidronate, which is
      a potent inhibitor of osteoclastic bone resorption. Symptom relief resulted for
      up to 3 months, but repeated courses of pamidronate have been required to
      maintain symptom control.

PMID- 11948080
TI  - Giant cell arteritis presenting with annuloaortic ectasia.
AB  - Four cases of giant cell arteritis causing severe aortic regurgitation secondary
      to an aneurysm of the ascending aorta are described. In two cases, the nature of
      the aortic pathology could be suspected considering the past clinical evidence of
      temporal arteritis and/or polymyalgia rheumatica. In the two other cases, the
      cardiothoracic manifestations represented the onset of Horton disease.

PMID- 11948081
TI  - North American paragonimiasis: case report of a severe clinical infection.
AB  - Paragonimiasis is an important cause of pulmonary disease worldwide. It results
      from an infection with Paragonimus, a parasite that reproduces through a complex
      life cycle involving snails, crustaceans, and mammals. Humans acquire the disease
      by ingesting uncooked freshwater crab or crayfish. Paragonimus species are
      distributed globally, and the disease is well known in endemic regions of Asia
      where culturally based methods of food preparation foster human transmission.
      Paragonimus also exists in regions of the United States but has been a rare cause
      of pulmonary disease. We report a case of a previously healthy young man who
      developed a dense empyema from Paragonimus kellicotti that ultimately required
      thoracotomy and praziquantel to eradicate his infection.

PMID- 11948082
TI  - Steady-state end-tidal alveolar dead space measure and D-dimer.

PMID- 11948083
TI  - Coronary endothelial dysfunction in patients with hypertrophic cardiomyopathy.

PMID- 11948084
TI  - Cryptogenic hemoptysis and smoking.

PMID- 11948085
TI  - Physician workforce and trainee planning.

PMID- 11948086
TI  - A diagnostic dilemma of syncope.

PMID- 11948087
TI  - Significant omission in antithrombotic supplement.

PMID- 11948089
TI  - Adenosine deaminase levels in nontuberculous lymphocytic pleural effusions.

PMID- 11948088
TI  - Nicotine reduction and bupropion.

PMID- 11948090
TI  - Doxapram and perception of dyspnea.

PMID- 11948091
TI  - Captain of the ship.

PMID- 11948095
TI  - End points in cancer clinical trials and the drug approval process.
AB  - The sequencing of the human genome and the elucidation of many molecular pathways
      important in cancer cell proliferation, apoptosis, and metastasis have provided
      unprecedented opportunities for development of new agents to prevent and treat
      cancer. The types of molecules in development are increasingly varied and include
      small molecules, monoclonal antibodies, antisense oligonucleotides, and
      ribozymes. Thus, the variety of anticancer agents in clinical development is now
      greater than ever before, and the number of agents currently in clinical trial
      for various cancer indications is estimated to exceed 400. Many of these drugs
      would be expected to work in only narrowly defined patient populations that must
      be prospectively identified. Thus, the development of the therapeutic agent must
      often be linked to the development of a molecular diagnostic product. Drugs that
      produce primarily cytostatic effects might not be expected to produce regression
      of tumor masses; thus, evaluation of such agents would best be done in
      populations of patients with low tumor burdens but high risk of disease
      progression. As traditional clinical end points prove more difficult to apply in
      evaluation of molecularly targeted therapies, a great need exists to define and
      validate surrogate markers of effect and of benefit. New clinical trial designs
      and end points are necessary to permit more efficient evaluation of putative
      cancer treatments. This editorial will review commonly used clinical trial end
      points and describe their potential advantages and disadvantages to expedite the
      drug approval process required in the United States.

PMID- 11948092
TI  - Bronchodilator reversibility to albuterol predicts bronchodilator response to
      salmeterol.

PMID- 11948096
TI  - Differentiation therapy for myelodysplastic syndrome.

PMID- 11948097
TI  - Increased sophistication of immunotoxins.

PMID- 11948098
TI  - Activated STAT signaling in human tumors provides novel molecular targets for
      therapeutic intervention.
AB  - The signal transducers and activators of transcription (STAT)factors function as
      downstream effectors of cytokine and growth factor receptor signaling. Compared
      with normal cells and tissues, constitutively activated STATs have been detected
      in a wide variety of human cancer cell lines and primary tumors. STATs are
      activated by tyrosine phosphorylation, which is normally a transient and tightly
      regulated process. In tumor cells, constitutive activation of STATs is linked to
      persistent activity of tyrosine kinases, including Src, epidermal growth factor
      receptor, Janus kinases, Bcr-Abl, and many others. Such oncogenic tyrosine
      kinases are often activated as a consequence of permanent ligand/receptor
      engagement in autocrine or paracrine cytokine and growth factor signaling or
      represent autonomous constitutively active enzymes as a result of genetic
      alterations found in tumor but not normal cells. Persistent signaling of specific
      STATs, in particular Stat3 and Stat5, has been demonstrated to directly
      contribute to oncogenesis by stimulating cell proliferation and preventing
      apoptosis. STATs participate in oncogenesis through up-regulation of genes
      encoding apoptosis inhibitors and cell cycle regulators such as Bcl-x(L), Mcl-1,
      cyclins D1/D2, and c-Myc. Inhibition of constitutively active STAT signaling
      pathways has been shown repeatedly to inhibit tumor cell growth in vitro and in
      vivo and provides a novel means for therapeutic intervention in human cancer. In
      this review, we will: (a) explain the mechanisms of STAT activation in normal and
      malignant signaling; (b) summarize recent evidence for the critical role of
      constitutively activated Stat3 and Stat5 in oncogenesis; (c) identify candidate
      STAT target genes implicated in tumor progression; and (d) discuss molecular and
      pharmacological strategies to interfere with STAT signaling for potential
      therapeutic intervention in human cancer.

PMID- 11948099
TI  - The potential of drug-carrying immunoliposomes as anticancer agents. Commentary
      re: J. W. Park et al., Anti-HER2 immunoliposomes: enhanced efficacy due to
      targeted delivery. Clin. Cancer Res., 8: 1172-1181, 2002.

PMID- 11948100
TI  - The Department of Defense Congressionally Directed Medical Research Program:
      innovations in the federal funding of biomedical research.
AB  - In response to the lobbying efforts of the women's advocacy movement, in 1993
      Congress authorized funds for a substantial increase in support of new and
      promising research aimed at the eradication of breast cancer. This appropriation
      resulted in a major expansion of the United States Army Medical Research and
      Materiel Command, Department of Defense Breast Cancer Research Program. The
      Office of Congressionally Directed Medical Research Programs was established
      within the United States Army Medical Research and Materiel Command to facilitate
      the management of the expanded extramural research program. Since that time, the
      programs have grown to include not just breast cancer but also prostate cancer,
      ovarian cancer, and neurofibromatosis. The unique appropriations to the Office of
      Congressionally Directed Medical Research Programs has resulted in a number of
      programmatic innovations. These include development of unique mechanisms of grant
      support, inclusion of consumer advocates on peer and programmatic review panels,
      and the introduction of criteria-based evaluation and scoring in peer review.
      This article describes these novel scientific management strategies and outlines
      their success in meeting program visions and goals.

PMID- 11948102
TI  - 2-[(18)F]Fluoro-2-deoxyglucose and glucose uptake in malignant gliomas before and
      after radiotherapy: correlation with outcome.
AB  - PURPOSE: To examine whether quantitative 1-[(11)C]glucose- or 2-[(18)F]fluoro-2
      deoxyglucose (FDG)-positron emission tomography performed before and/or after
      radiotherapy (RT) of malignant gliomas correlates with treatment outcome. Changes
      in metabolism between the start and finish of RT, and immediate post-RT studies
      have received little attention. EXPERIMENTAL DESIGN: Adults with malignant
      gliomas were imaged within 2 weeks before and/or 2 weeks after RT. Four patients
      were imaged only before RT, 12 only after RT, and 14 both before and after RT.
      Each 1-[(11)C]glucose and FDG study included arterial plasma sampling. Kinetic
      parameters, glucose metabolic rate (MRGlc), and FDG metabolic rate (MRFDG) were
      estimated by an optimization program based on a three compartment, four rate
      constant model. Changes in MRGlc or MRFDG from pre-RT to post-RT were calculated
      for the 14 patients studied at both times. Overall survival was examined, and
      survival was computed relative to historical controls in matched prognostic
      classes. RESULTS: Low pre-RT MRGlc (P < 0.02) or MRFDG (P < 0.03), or an increase
      from pre- to post-RT in MRGlc (P < 0.004) or MRFDG (P < 0.006) are correlating
      with longer survival (4 patients still alive). Strikingly, the post-RT studies (n
      = 26) showed no correlation between MRGlc or MRFDG and survival (P = 0.73 and P =
      0.46 respectively). CONCLUSIONS: Low MRGlc or MRFDG before RT probably indicates
      less aggressive disease. An increase in MRGlc or MRFDG from pre- to post-RT in
      the tumors of patients with longer survival could be because of one or more of
      the following or other reasons: (a) apoptosis of tumor cells in response to RT
      requires energy; (b) decreased tumor cell density by the RT leaving normal cells
      with higher metabolism; or (c) inflammatory cells infiltrate and take up glucose
      or FDG where tumor cells are dying. Quantitative 1-[(11)C]glucose or FDG uptake
      in the early weeks post-RT correlates poorly with survival.

PMID- 11948103
TI  - p14ARF promoter hypermethylation in plasma DNA as an indicator of disease
      recurrence in bladder cancer patients.
AB  - PURPOSE: Several genes are reported to be implicated in bladder carcinogenesis,
      including p53, p16INK4a, pRb, erbB-2, Cyclin D1, H-ras, EGFR, and c-myc. Gene
      alterations in plasma DNA identical to those observed within the tumor have been
      detected in various types of neoplasia. EXPERIMENTAL DESIGN: We analyzed loss of
      heterozygosity in six microsatellite markers (D17S695, D17S654, D13S310, TH2,
      D9S747, and D9S161), p53 and K-ras mutations, and the promoter status of p14ARF
      and p16INK4a in the mononuclear normal blood cells, tumor, and plasma DNA of 27
      bladder cancer patients. We also studied the distribution of several
      clinicopathological parameters in these patients in regard to molecular
      alterations. RESULTS: Seventeen (63%) cases displayed the same alteration in
      plasma and tumor DNA (some patients showed more than one alteration
      simultaneously). Plasma p14ARF promoter hypermethylation was associated with the
      presence of multicentric foci (P = 0.03), larger tumors (P = 0.01), and relapse
      of the disease (P = 0.03). Plasma loss of heterozygosity was also linked to
      disease recurrence (P = 0.02). CONCLUSIONS: The results indicate that p14ARF
      aberrant promoter methylation could be involved in bladder carcinogenesis and
      that plasma DNA is a potential prognostic marker in urinary bladder cancer.

PMID- 11948101
TI  - Impact of prolonged infusions of the putative differentiating agent sodium
      phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia.
AB  - The aromatic fatty acid sodium phenylbutyrate (PB) promotes cytostasis and
      differentiation in a wide variety of tumor types; among several molecular
      activities, inhibition of histone deacetylase (HDAC) may account for many of its
      pharmacodynamic effects. A Phase I study demonstrated promising preliminary
      evidence of clinical activity in acute myeloid leukemia and myelodysplastic
      syndrome; however, plasma concentrations achieved at the maximum tolerated dose
      were less than those targeted based on in vitro studies. Because prolonged
      exposure to suboptimal concentrations of PB in vitro led to pharmacodynamic
      changes similar to a more brief exposure to higher concentrations, a study of the
      feasibility of prolonged administration of sodium PB was performed. Selected
      patients with acute myeloid leukemia and myelodysplastic syndrome were treated
      with sodium PB as a continuous i.v. infusion via ambulatory infusion pump.
      Sequential cohorts were treated for 7 consecutive days out of 14 or with 21
      consecutive days out of 28. Prolonged infusions were well tolerated; dose
      limiting central nervous system toxicity developed in 1 of 23 patients treated.
      End-of-infusion plasma concentrations were maintained within a range sufficient
      to inhibit HDAC. Two patients on the 21/28 schedule developed hematological
      improvement. Prolonged infusions of PB are well tolerated making this an
      attractive platform for the clinical investigation of HDAC inhibition.

PMID- 11948104
TI  - Circulating Epstein-Barr virus DNA in serum of patients with lymphoepithelioma
      like carcinoma of the lung: a potential surrogate marker for monitoring disease.
AB  - PURPOSE: The purpose of this work was to study the sera of patients with
      lymphoepithelioma-like carcinoma (LELC) of the lung for circulating EBV DNA.
      EXPERIMENTAL DESIGN: Prospectively collected serum samples from five female
      patients with advanced, inoperable LELC of the lung were measured for free
      circulating EBV DNA using a quantitative PCR technique. EBV-encoded small RNA
      (EBER)-1 was assayed in serial serum samples of three of the five patients,
      either from the start or during the initial phase of chemotherapy/radiotherapy
      until their terminal event or last follow-up. There was only a single-point
      sample for analysis in the fourth and fifth patients. Six other patients with
      LELC of the lung were also retrospectively identified, and their sera were tested
      for EBER-1 at either the first visit plus the last follow-up visit (n = 2), the
      first visit only (n = 2), or the last follow-up visit only (n = 2). RESULTS:
      Prospectively collected serum samples from five patients and retrospectively
      collected serum samples from two patients who had clinical disease at initial
      serum measurement showed detectable levels of EBER-1. Retrospectively collected
      serum samples from four patients with no clinical disease had negative sera.
      There is consistent correlation between the clinical response to treatment and
      subsequent clinical course of LELC and serum EBER-1 levels in the three
      prospective patients with longitudinal serum monitoring. CONCLUSIONS: This study
      shows for the first time that free EBV DNA can be detected in the serum of
      patients with LELC of the lung and further suggests the feasibility of its use
      for monitoring response to therapy in advanced cases.

PMID- 11948105
TI  - Improved cytotoxic activity toward cell lines and fresh leukemia cells of a
      mutant anti-CD22 immunotoxin obtained by antibody phage display.
AB  - Recombinant immunotoxins are fusion proteins composed of the Fv domains of
      antibodies fused to bacterial or plant toxins that are being developed for the
      targeted therapy of cancer. RFB4 (Fv)-Pseudomonas exotoxin 38 (PE38) is an
      immunotoxin that targets CD22 expressed on B cells and B-cell malignancies. A
      disulfide-stabilized form of RFB4 (Fv)-PE38 is being evaluated in a Phase I
      clinical trial. The aim of the present study was to improve the activity of RFB4
      (Fv)-PE38 to more effectively treat patients with leukemias and lymphomas. To
      increase the affinity of RFB4 (Fv), we used the techniques of phage display and
      hot spot mutagenesis. We identified mutational hot spot sequences in heavy chain
      complementary determining region 3 (V(H) CDR3) and randomized these in a phage
      display library. Mutant phages were panned on CD22-positive Daudi cells. A
      variety of mutant Fvs were obtained, and the corresponding immunotoxins were
      prepared. Several mutant immunotoxins with increased binding affinity and
      cytotoxic activity were obtained. The most active immunotoxin contained amino
      acid residues Thr-His-Trp (THW) in place of Ser-Ser-Tyr (SSY) at positions 100,
      100A, and 100B of the Fv and had an affinity improved from 85 nM to 6 nM. The THW
      mutant had a 5- to 10-fold increase in activity on various CD22-positive cell
      lines and was up to 50 times more cytotoxic to cells from patients with chronic
      lymphocytic leukemia and hairy-cell leukemia.

PMID- 11948106
TI  - Inhibition of androgen-independent growth of prostate cancer xenografts by 17beta
      estradiol.
AB  - PURPOSE: Estrogen treatment has long been known to be of benefit in prostate
      cancer (CaP), but its mechanism was thought to involve merely a reduction in
      androgen levels. However, new evidence indicates that estrogen may exert effects
      on CaP cells in the absence of androgens. EXPERIMENTAL DESIGN: Implantation of
      CaP xenografts (LuCaP 35, LuCaP 49, LuCaP 58, LuCaP 73, PC-3, and LNCaP) into
      intact and ovariectomized female mice was done to characterize growth and take
      rates in the absence of androgens. Ovariectomized female mice were supplemented
      with 17beta-estradiol, and LuCaP 35 CaP xenograft take and growth rates were
      determined. Reverse transcription-PCR was used to evaluate the presence of the
      estrogen receptor messages in CaP xenografts. RESULTS: We have observed
      significant inhibition of CaP growth in intact versus ovariectomized female
      animals in five of six CaP xenograft lines. 17beta-Estradiol supplements given to
      ovariectomized female mice led to inhibition of tumor establishment and
      diminished growth of LuCaP 35 similar to that observed in intact female mice.
      Using reverse transcription-PCR, we have shown that these xenografts express the
      estrogen receptor beta message. CONCLUSIONS: We have determined that 17beta
      estradiol supplementation causes inhibition of CaP growth in an animal model by
      mechanisms that are independent of androgen action. This gives rise to the
      possibility that estrogen therapy may be of potential use with hormone-refractory
      cancers. The xenograft models we describe herein may be useful as well in
      elucidating the pathways mediating the androgen-independent effects of estrogen
      on CaP.

PMID- 11948107
TI  - Role of host microenvironment in angiogenesis and microvascular functions in
      human breast cancer xenografts: mammary fat pad versus cranial tumors.
AB  - PURPOSE: The host microenvironment differs between primary and metastatic sites,
      affecting gene expression and various physiological functions. Here we show the
      differences in the physiological parameters between orthotopic primary and
      metastatic breast tumor xenografts using intravital microscopy and reveal the
      relationship between angiogenic gene expression and microvascular functions in
      vivo. EXPERIMENTAL DESIGN: ZR75-1, a human estrogen-dependent mammary carcinoma,
      was implanted into the mammary fat pad (primary site) of ovariectomized SCID
      female mice carrying estrogen pellets. The same tumor line was also grown in the
      cranial window (metastasis site). When tumors reached the diameter of 2.5 mm,
      angiogenesis, hemodynamics, and vascular permeability were measured by intravital
      microscopy, and expression of angiogenic growth factors was determined by
      quantitative reverse transcription-PCR. RESULTS: ZR75-1 tumors grown in the
      mammary fat pad had higher microvascular permeability but lower vascular density
      than the same tumors grown in the cranial window (2.5- and 0.7-fold,
      respectively). There was no significant difference in RBC velocity, vessel
      diameter, blood flow rate, and shear rate between two sites. The levels of
      vascular endothelial growth factor (VEGF), its receptors VEGFR1 and VEGFR2, and
      angiopoietin-1 mRNA tended to be higher in the mammary fat pad tumors than in the
      cranial tumors (1.5-, 1.5-, 3-, and 2-fold, respectively). CONCLUSIONS: The
      primary breast cancer exhibited higher vascular permeability, but the cranial
      tumor showed more angiogenesis, suggesting that the cranial environment is
      leakage resistant but proangiogenic. Collectively, host microenvironment is an
      important determinant of tumor gene expression and microvascular functions, and,
      thus, orthotopic breast tumor models should be useful for obtaining clinically
      relevant information.

PMID- 11948108
TI  - Therapeutic potential of a reduced-intensity preparative regimen for allogeneic
      transplantation with cladribine, busulfan, and antithymocyte globulin against
      advanced/refractory acute leukemia/lymphoma.
AB  - PURPOSE: Cladribine (2-CdA) is a purine analogue that exhibits activity against a
      variety of hematological malignancies and has a potent immunosuppressive effect.
      We therefore performed a pilot study to evaluate the feasibility of a novel 2-CdA
      based reduced-intensity stem cell transplantation (RIST) regimen. EXPERIMENTAL
      DESIGN: A total of 16 scheduled patients with hematological malignancies were
      enrolled for comparison of their data with conventional stem cell transplantation
      (n = 19). The regimen for RIST consisted of 2-CdA (0.11 mg/kg/day for 6 days),
      busulfan (4 mg/kg/day for 2 days), and rabbit antithymocyte globulin (2.5
      mg/kg/day for 4, 2, or 0 days). The underlying diseases included acute
      myelogenous leukemia (n = 6), chronic myelogenous leukemia (n = 2),
      myelodysplastic syndrome (n = 6), and non-Hodgkin's lymphoma (n = 2). RESULTS:
      After RIST, four patients died before day 100 as a result of acute graft-versus
      host disease (n = 1), bacteremia (n = 1), disseminated candidasis (n = 1) and
      congestive heart failure (n = 1). Another patient died of cerebral infarction on
      day 140. Thus, acute-phase regimen-related toxicities >grade III were observed in
      only one patient. Engraftment and complete donor chimerism were achieved by day
      28 in 14 evaluable patients, and 6 of them (43%) experienced grade II-IV acute
      graft-versus-host disease. With a median follow-up of 328 days (range, 231-633
      days), the actuarial 1-year overall and disease-free survival rates were 69% and
      50%, respectively. Notably, among seven high-risk patients (five patients had
      been in complete remission two or more times and two not in complete remission
      with refractory disease at transplant), only two patients developed leukemia
      relapse after RIST. Although the recovery of CD4+ cells was significantly slower
      (P = 0.02) in RIST than in conventional stem cell transplantation, the incidence
      of clinically documented infections was not significantly different between the
      two groups. CONCLUSION: The results suggest that this novel regimen containing 2
      CdA is well tolerated and induces early complete donor chimerism. The unexpected
      durable remission achieved in patients with advanced disease at transplant
      suggests the presence of an acceptable antileukemia/lymphoma effect, which would
      warrant a further clinical trial.

PMID- 11948109
TI  - A phase I trial of tumor lysate-pulsed dendritic cells in the treatment of
      advanced cancer.
AB  - PURPOSE: The objectives of this study were to assess the toxicity and
      immunological response induced by the intradermal (i.d) administration of tumor
      lysate-pulsed dendritic cells (DCs). EXPERIMENTAL DESIGN: Patients with stage IV
      solid malignancies were treated in cohorts that received 10(6), 10(7), and 10(8)
      DCs i.d. every 2 weeks for three vaccines. Each vaccine was composed of a mixture
      of half DCs pulsed with autologous tumor lysate and the other half with keyhole
      limpet hemocyanin (KLH). Peripheral blood mononuclear cells (PBMCs) harvested 1
      month after the last immunization was compared with pretreatment PBMCs for
      immunological response. Delayed-type hypersensitivity reactivity to tumor antigen
      and KLH was also assessed. RESULTS: Fourteen patients received all three vaccines
      and were evaluable for toxicity and/or immunological monitoring. There were no
      grade 3 or 4 toxicities associated with the vaccines or major evidence of
      autoimmunity. Local accumulation of CD4(+) and CD8(+) T cells were found at the
      vaccination sites. There was a significant proliferative response of PBMCs to KLH
      induced by the vaccine. In 5 of 6 patients, the vaccine resulted in increased IFN
      gamma production by PBMCs to KLH in an ELISPOT assay. Using the same assay, 3 of
      7 patients' PBMCs displayed increased IFN-gamma production in response to
      autologous tumor lysate. One patient with melanoma also was observed to have an
      increased frequency of MART-1- and gp100-reactive CD8(+) T cells after
      vaccination. By delayed-type hypersensitivity testing, 8 of 9 and 4 of 10
      patients demonstrated reactivity to KLH and autologous tumor, respectively. Two
      patients with melanoma experienced a partial and a minor response, respectively.
      CONCLUSION: The administration of tumor lysate-pulsed DCs is nontoxic and capable
      of inducing immunological response to tumor antigen. Additional studies are
      necessary to improve tumor rejection responses.

PMID- 11948110
TI  - Phase I and pharmacokinetics study of crotoxin (cytotoxic PLA(2), NSC-624244) in
      patients with advanced cancer.
AB  - A Phase I clinical trial was performed on patients with solid tumors refractory
      to conventional therapy. Crotoxin was administered i.m. for 30 consecutive days
      at doses ranging from 0.03 to 0.22 mg/m(2). Patients entered the study after
      providing a written informed consent. Although 26 patients were entered only 23
      were evaluated. Reversible, nonlimiting neuromuscular toxicity evidenced as
      diplopia because of pareses of the external ocular muscles was present in 13
      patients. It started at doses of 0.18 mg/m(2) and lasted from 2 to 6 h. These
      episodes did not require dose adjustment and disappeared in 1-3 weeks of
      treatment. Three patients experienced palpebral ptosis, nystagmus (grade 2), and
      anxiety (grade 2-3) at the dose-limiting toxicity of 0.22 mg/m(2). Also at dose
      limiting toxicity, 1 patient showed nystagmus (grade 2) and anxiety (grade 3)
      without evidence of palpebral ptosis. Transient increases (grades 1-3) in the
      levels of creatinine kinase, aspartate aminotransferase, and alanine transaminase
      attributed to crotoxin myotoxicity were observed but returned to normal by the
      last week of treatment. At 0.21 mg/m(2) there was a case of grade-3 anaphylactic
      reaction on day 31, which required treatment. Hypersensitivity was regarded as an
      adverse drug-related reaction, and the patient was removed from the protocol. Two
      patients at different doses (0.12 mg/m(2) and 0.22 mg/m(2)) had sialorrhea. Four
      patients had asymptomatic transient increase in blood pressure (up to 20 mm Hg)
      12 h after the first injection, which lasted 24 h. No treatment was required and
      toxicity did not reappear. Six patients experienced slight eosinophilia during
      the first 2 weeks. The maximum tolerated dose was set at 0.21 mg/m(2). Objective
      measurable partial responses (>50% reduction of tumor mass) were noted in 2
      patients treated at 0.21 mg/m(2) and 1 at 0.12 mg/m(2). One patient (at 0.21
      mg/m(2)) presented a complete response on day 110. Crotoxin pharmacokinetics
      showed rapid absorption from the injection site to blood (t(1/2 A) = 5.2 +/- 0.6
      min). Plasma concentration reached a peak (C(max) = 0.79 +/- 0.1 ng/ml) at
      tau(max) = 19 +/- 3 min. The half-life of the distribution (alpha) phase is 22 +/
      2 min. Starting at 1.5 h after injection, the decrease in plasma concentration
      becomes slower, reaching 14 +/- 3 pg/ml 24 h after injection. The profile is
      dominated by the elimination (beta) phase with a half-life of 5.2 +/- 0.6 h.
      Consequently, 24 h after the injection ( approximately 5 half-life) 97% of the
      product was eliminated. The area under plasma concentration versus time curve was
      0.19 +/- 0.05 microg/min/ml. Assuming availability (F) approximately 1, the
      clearance is C(L) = 26.3 +/- 7 ml/min, and the apparent volume of distribution is
      V(d) = 12 +/- 3 liter/kg. The recommended dose for a Phase II study is 0.18
      mg/m(2).

PMID- 11948112
TI  - Importance of serum hemoglobin in hormone refractory prostate cancer.
AB  - OBJECTIVES: In the search for an early measure of response in hormone refractory
      prostate cancer (HRPC), most have targeted changes in serum prostate-specific
      antigen (PSA). Up to this point, no one has targeted changes in serum hemoglobin
      during treatment. If dynamic changes in hemoglobin after treatment provide
      additive prognostic information to dynamic changes in PSA, then we should
      consider and test ways to incorporate serum hemoglobin into measures of response
      in HRPC. METHODS: Our patients consisted of 321 men who were studied on Cancer
      and Leukemia Group B protocols 9181 and 9182. We fit serial values of PSA and
      hemoglobin with an exponential model: y = exp(alpha + beta*t + gamma*t(2)) with y
      symbolizing either PSA or hemoglobin and t denoting time. We then used the Cox
      proportional hazard model to relate the parameters of the model (alpha, beta, and
      gamma) to subsequent survival. RESULTS: We found that the exponential model fit
      serial measurements of both PSA and serum hemoglobin well, and all three of the
      parameters for both markers related closely to subsequent survival (P < or =
      0.003). The Cox model suggested a composite hazard score (HS) as a way to
      consolidate the information from serial measurements of both serum markers, and
      we observed that those with HS < 0 enjoyed a longer survival. CONCLUSION: Because
      serial measurements of serum hemoglobin during treatment of HRPC add prognostic
      information to serial measurements of PSA, we hypothesize that combining the
      dynamic changes in serum hemoglobin with those of PSA could lead to an improved
      measure of response in HRPC.

PMID- 11948111
TI  - Phase I clinical and pharmacokinetic study of protein kinase C-alpha antisense
      oligonucleotide ISIS 3521 administered in combination with 5-fluorouracil and
      leucovorin in patients with advanced cancer.
AB  - The present study was designed to determine the maximum tolerated dose (MTD),
      toxicity profile, pharmacokinetics (PKs), and antitumor activity of the protein
      kinase C-alpha antisense oligonucleotide ISIS 3521 (ISIS Pharmaceuticals, Inc.,
      Carlsbad, CA) when administered in combination with 5-fluorouracil (5-FU) and
      leucovorin (LV). Patients with refractory solid tumors received ISIS 3521 as a 21
      day continuous infusion administered simultaneously with 5-FU and LV given daily
      for 5 days repeated every 4-5 weeks (one cycle). 5-FU and ISIS 3521 PK analysis
      were performed on samples taken during the first cycle in all patients. Fifteen
      patients received ISIS 3521 at one of three dose levels: (a) 1.0 (n = 3
      patients); (b) 1.5 (n = 3 patients); and (c) 2.0 (n = 9 patients) mg/kg/day. All
      patients simultaneously received 5-FU (425 mg/m(2)/day) and LV (20 mg/m(2)/day)
      for 5 consecutive days. Grade 1-2 toxicities included alopecia, fatigue,
      mucositis, diarrhea, anorexia, nausea/vomiting, and tumor pain. One patient had
      grade 3 chest pain considered to be related to 5-FU therapy, another patient had
      dose-limiting grade 3 mucositis resolving in <7 days, and one patient with a
      history of gastritis had an acute upper gastrointestinal bleed thought to be 5-FU
      induced toxicity. Five patients developed cycle 1 grade 4 neutropenia, which
      resolved without colony-stimulating factors before the next treatment cycle.
      There were no effects on prothrombin time and activated partial thromboplastin
      time. A clinically defined MTD was not reached. The character and severity of
      these toxicities do not seem to be dose related, and, as such, there was no
      classical dose-limiting toxicity defining the MTD. ISIS 3521 PKs in the presence
      of 5-FU was consistent with those reported previously. 5-FU PK parameters were
      also similar in the presence or absence of ISIS 3521. Six of 14 patients (
      approximately 43%) across all dose cohorts had an improvement in measurable tumor
      response ranging from minor reduction in tumor size (4 patients) to objective
      partial response (>50% reduction in tumor size, 2 patients). ISIS 3521 is
      tolerable at its recommended single-agent dose when given with 5-FU and LV. There
      is no apparent PK interaction between ISIS 3521 and 5-FU and LV. Antitumor
      activity was observed with the combination; however, it is uncertain whether
      clinical activity is a result of enhanced drug interaction. Our study warrants
      further exploration of efficacy in a Phase II and/or Phase III clinical trial
      setting.

PMID- 11948113
TI  - Regulation of stromal versican expression by breast cancer cells and importance
      to relapse-free survival in patients with node-negative primary breast cancer.
AB  - PURPOSE: Determination of meaningful prognostic indicesremains a high priority
      for women diagnosed with node-negative primary breast cancer. Currently, 30% of
      these women relapse, and there is no reliable means of predicting this group of
      patients. This study investigates whether the level of expression of versican, an
      anticell adhesive proteoglycan, in the peritumoral stromal tissue of women with
      node-negative, primary breast cancer predicts relapse-free survival. This study
      also examines whether breast cancer cells regulate the secretion of versican by
      mammary fibroblasts. EXPERIMENTAL DESIGN: Immunoreactive versican was measured in
      breast cancer tissue sections of 58 node-negative patients by video image
      analysis. Primary isolates of mammary fibroblasts were cultured in medium
      conditioned by the breast cancer cell lines ZR-75-1, MCF-7, BT-20, and MB231.
      Changes in versican secretion were measured by immunoblotting and enhanced
      chemiluminescence. RESULTS: Cox analyses indicated that peritumoral versican
      level was the sole predictor of relapse-free survival. The relapse rate in
      patients with low versican levels was lower than in patients with high versican
      levels (Kaplan-Meier: 83% relapse free at 5 years for versican mean integrated
      absorbance <14 versus 33% for > or = 14, P = 0.0006). Accumulation of versican in
      medium of mammary fibroblasts was increased after culture in conditioned medium
      from breast cancer cell lines. CONCLUSIONS: Relapse in women with node-negative
      breast cancer is related to the level of versican deposited in peritumoral stroma
      by mammary fibroblasts. Versican secretion appears to be regulated by breast
      cancer cell mediators. Neoplastic remodeling of extracellular matrix through
      increased versican deposition may facilitate local invasion and metastasis.

PMID- 11948114
TI  - Amplification and overexpression of topoisomerase IIalpha predict response to
      anthracycline-based therapy in locally advanced breast cancer.
AB  - PURPOSE: The putative association between erbB-2 overexpression and favorable
      response to anthracyline-based therapy in breast cancer is controversial, and the
      mechanism unclear. We sought to determine whether coamplification and
      overexpression of the topoisomerase IIalpha gene, near erbB-2 on chromosome 17,
      and a known anthracycline target, may underlie the association. EXPERIMENTAL
      DESIGN: Thirty-five patients who had locally advanced breast cancer (LABC) and
      who had received neoadjuvant, anthracycline-based therapy were studied. Copy
      number of topoisomerase IIalpha and erbB-2 was determined by fluorescence in situ
      hybridization, and expression by immunohistochemistry. RESULTS: Of 8 patients
      with erbB-2 amplification, 5 had a complete response (CR) or minimal residual
      disease (MRD), 3 had a partial response (PR), and none had stable (StD) or
      progressive disease (PD) at the time of mastectomy, versus 3 CR or MRD, 16 PR,
      and 8 StD or PD for patients without amplification (P = 0.008). In contrast, erbB
      2 overexpression was not significantly associated with response (P = 0.114). Of 6
      patients with topoisomerase IIalpha amplification, 4 had CR or MRD, 2 PR, and
      none StD or PD, versus 4 CR or MRD, 17 PR, and 8 StD or PD for patients without
      amplification (P = 0.034). All of the tumors with topoisomerase IIalpha
      amplification also had erbB-2 amplification, but not vice versa. Overexpression
      of topoisomerase IIalpha (9 patients) was also associated with favorable response
      (P = 0.021). CONCLUSIONS: Coamplification of erbB-2 and topoisomerase IIalpha is
      significantly associated with favorable local response to anthracycline-based
      therapy in LABC. The expression data favor a plausible mechanism based on
      topoisomerase IIalpha biology.

PMID- 11948115
TI  - Expression of the breast cancer resistance protein in breast cancer.
AB  - PURPOSE: The breast cancer resistance protein (BCRP) is involved in in vitro
      multidrug resistance and was first identified in the breast cancer cell line
      MCF7/AdrVp. The aim of this study was to investigate the role of BCRP in
      resistance of breast cancer to anthracycline treatment. EXPERIMENTAL DESIGN: BCRP
      mRNA was determined with real-time reverse transcription-PCR and immunostaining
      in nine breast cancer cell lines and in samples of 25 primary breast carcinomas
      and 27 patients who received preoperative anthracycline-based therapy. Tumor
      response to treatment and patient survival were recorded. RESULTS: In cell lines,
      only MCF7 and BT20 had BCRP mRNA levels coinciding with membrane-bound
      immunostaining. In clinical samples, BCRP expression varied widely (range, 0.01
      0.86). With immunohistochemistry, BCRP was detected in vessels and normal breast
      epithelium but not in tumor cells. There was no difference in BCRP expression
      between anthracycline-naive and treated tumor samples. BCRP expression was not
      associated with decreased response or survival. CONCLUSIONS: There is no
      indication that elevated BCRP expression in breast carcinomas confers resistance
      to anthracyclines. Expression was not detectable with immunohistochemistry.

PMID- 11948116
TI  - Minichromosome maintenance protein 2 expression in normal kidney and renal cell
      carcinomas: relationship to tumor dormancy and potential clinical utility.
AB  - PURPOSE: A major problem in the management of patients with renal cell carcinoma
      is predicting tumor behavior. In the search for more accurate markers of
      prognosis, tumor cell proliferation has been investigated. These studies have
      mostly used antibodies directed against Ki-67 or proliferating cell nuclear
      antigen and have given conflicting results, findings that are likely because of a
      combination of specificity and methodological differences. Minichromosome
      maintenance (Mcm) proteins are a series of closely related proteins that are
      components of the prereplicative complex. The Mcm proteins are essential for
      initiating eukaryotic DNA replication and serve as useful markers of
      proliferating cells. EXPERIMENTAL DESIGN: The aims of this study were to
      determine the frequency and pattern of Mcm2 expression by immunohistochemistry in
      normal kidney (n = 10) and renal tumors [n = 56; clear cell n = 36; chromophil
      (papillary) n = 7; oncocytoma n = 5; and transitional cell carcinoma n = 8],
      compare its sensitivity to the established proliferation marker Ki-67, examine
      for differences in tumors derived from stable and labile epithelial cell
      populations in the kidney, and assess the relationship of Mcm2 proliferation to
      clinicopathological characteristics of kidney tumors. In addition, to
      additionally investigate the issue of tumor dormancy we wished to assess the
      relationship between Mcm2 labeling index (LI) and the angiogenic factors
      angiopoietin-1 (Ang) and Ang-2. RESULTS: In normal tissues, Mcm2 nuclear labeling
      was identified in both glomeruli (LI median 0.35%; range 0-1.7) and renal tubules
      (LI median 0.3%; range 0.1-2.9%). In tumors Mcm2 labeling was predominantly at
      the periphery with LIs ranging from 0.2-91.5%, which was significantly greater
      than Ki-67 LI (0.2-40.5%; P < 0.001). Mcm2 LI was also significantly higher in
      tumors derived from a labile epithelium (transitional cell carcinomas) than a
      stable epithelium (renal cell carcinomas; P = 0.013). A significant association
      was also demonstrated between Mcm2 LI and tumor grade (P = 0.0006), and
      angiogenic phenotype (defined by Ang expression; P = 0.03) but not with patient
      age (P = 0.84), patient sex (P = 0.25), tumor size (P = 0.74), or stage (P =
      0.33). Furthermore, although not significant, a survival analysis demonstrated
      that 100% of patients with a low Mcm2 LI survived compared with 84% of those with
      a high Mcm2 LI over the follow-up period (up to 53.2 months; P = 0.14).
      CONCLUSIONS: This is the first study examining Mcm2 protein in normal and tumor
      kidney samples, and the first to perform histological subgroup analysis. It shows
      that Mcm2 is a superior marker to Ki-67 in the assessment of cell cycle entry in
      histological archival material and that normal kidney has a subset of cells
      within the glomerular and tubular compartments that are in cycle. It demonstrates
      that the frequency of cells in cycle in tumors formed from stable or labile
      epithelial populations mirrors that in the nonneoplastic epithelium. This study
      additionally demonstrates that the number of cells in cycle in tumors is limited
      by the angiogenic phenotype and supports animal models that show angiogenesis
      determines the likelihood of tumor dormancy. Additional study to confirm the
      clinical utility of Mcm2 as a prognostic marker is now indicated.

PMID- 11948117
TI  - Quantitative reverse transcription-polymerase chain reaction measurement of HASH1
      (ASCL1), a marker for small cell lung carcinomas with neuroendocrine features.
AB  - PURPOSE: The Human Achaete-Scute homologue 1 (HASH1, ASCL1), a lineage-specific
      basic helix-loop-helix member of the achaete-scute family, is essential for the
      generation of pulmonary neuroendocrine (NE) cells during lung development. In
      small cell lung cancer (SCLC), the most lethal form of lung cancer, the gene is
      highly expressed and the expression of HASH1 correlates with NE features found in
      SCLCs. Here we describe a highly sensitive reverse transcription-PCR method for
      quantifying HASH1 mRNA in clinical samples, using real-time fluorescence
      resonance energy transfer technology (LightCycler). EXPERIMENTAL DESIGN: The
      HASH1-positive NE cell line NCI-H187 was compared with the non-NE cell line NCI
      N417 by quantitative reverse transcription-PCR. Signals were normalized using the
      housekeeping gene PBGD, which is pseudogene free. Subsequently, HASH1 expression
      in RNA isolated from biopsies from SCLC patients (n = 4) was compared with
      biopsies from non-SCLC (NSCLC) patients (n = 2) or normal bronchus (n = 2).
      RESULTS: The HASH1-positive NE cell line NCI-H187 showed 50,000-fold higher
      normalized expression of HASH1 than did the non-NE cell line NCI-N417, indicating
      that the method is applicable over a wide dynamic range. Normalized average mRNA
      expression levels in SCLC clinical samples were 1,000-fold higher than in the
      NSCLC samples. Expression in normal bronchus was comparable to the expression
      levels in the NSCLC. CONCLUSIONS: These results show that marked and measurable
      differences exist between SCLCs and other lung tissues (either NSCLC or normal
      bronchus). We show that the method is applicable to small biopsy samples and can
      discriminate SCLC from NSCLC. This method could contribute to diagnosis based on
      molecular profiling of tumors.

PMID- 11948118
TI  - Silencing of GSTP1 gene by CpG island DNA hypermethylation in HBV-associated
      hepatocellular carcinomas.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: Glutathione S-transferases, enzymes that defend
      cells against damage mediated by oxidant and electrophilic carcinogens, may be
      critical determinants of cancer pathogenesis. In this report, we assess the role
      of epigenetic silencing of the GSTP1 gene, a gene encoding the pi-class
      glutathione S-transferase, in the pathogenesis of hepatitis B virus (HBV)
      associated hepatocellular carcinomas (HCC). The cell lines Hep3B, HepG2, and a
      cohort of 43 HBV-associated HCC tissue specimens and corresponding nontumor
      tissues were subjected to analysis for GSTP1 epigenetic alteration and
      expression. GSTP1 "CpG" island DNA hypermethylation in the liver cell lines, and
      the tissue specimens were determined by methylation-specific PCR and correlated
      with expression of the gene using reverse-transcription PCR, immunoblotting, and
      immunohistochemistry. RESULTS: GSTP1 CpG island DNA hypermethylation was detected
      in 28 of 43 (65.1%) HCC tissues and 4 of 40 (10%) corresponding nontumor tissues.
      GSTP1 protein was absent in those cases showing hypermethylation of the gene.
      Similarly, DNA from Hep3B and HepG2 cell lines displayed complete GSTP1
      hypermethylation in the CpG island, and they failed to express GSTP1 mRNA and the
      corresponding protein product. Treatment of the cell lines with the DNA
      methyltransferase inhibitor 5-aza-deoxycytidine reversed the hypermethylation,
      and restored GSTP1 mRNA and polypeptide expression. CONCLUSIONS: These data
      indicate that epigenetic silencing of GSTP1 gene expression by CpG island DNA
      hypermethylation is common in human HBV-associated HCC. In addition, somatic
      GSTP1 inactivation via CpG island hypermethylation may contribute to the
      pathogenesis of this malignancy.

PMID- 11948119
TI  - Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations.
AB  - BACKGROUND: The role of human papilloma virus (HPV) in the pathogenesis and
      biological behavior of tonsillar squamous cell carcinoma (TSCC) are areas of
      intense investigation. METHODS: This study used PCR analysis to identify HPV in
      paraffin-embedded tonsillar and nodal tissue from 52 patients with TSCC and 48
      age (+/-5 year)/gender-matched controls with benign tonsillar hyperplasia.
      Results were correlated with HLA-DRB1 haplotype and clinical outcome. RESULTS:
      HPV was identified in 46% of patients with TSCC and 6% of controls. DNA
      sequencing showed the presence of HPV type 16 in 21 patients (40%) with TSCC.
      There was no statistically significant association between HLA-DRB1 expression
      and TSCC or HPV infection. Fifteen of 16 patients with HPV-positive TSCC with
      regional metastases had evidence of HPV in pathologically involved lymph nodes.
      In eight HPV 16-positive TSCC patients with lymph node metastasis, PCR testing
      identified HPV 16 in 17 of 23 histologically negative lymph nodes. Patients with
      HPV-positive TSCC without metastatic disease had no evidence of HPV in their
      lymphatic tissue. Clinically, HPV-associated carcinoma was present in younger
      patients in comparison with HPV-negative TSCC patients (mean age, 56.6 versus 66
      years; P = 0.001). The odds for patients with HPV infection to develop TSCC were
      18.2 times greater than for patients without HPV infection (95% confidence
      interval 4.6, 73.1). There was no statistically significant association between
      presence of HPV and cause-specific survival (hazard ratio = 2.5 for HPV negative
      versus positive; P = 0.26), after adjusting for age in a Cox proportional hazards
      regression analysis. CONCLUSION: HPV is an independent risk factor for TSCC.
      Identification of HPV in the histologically positive and negative lymph nodes of
      patients with HPV-positive TSCC/metastatic disease supports the role of HPV in
      the oncogenesis of TSCC.

PMID- 11948120
TI  - Expression of the serine protease matriptase and its inhibitor HAI-1 in
      epithelial ovarian cancer: correlation with clinical outcome and tumor
      clinicopathological parameters.
AB  - PURPOSE: Matriptase is a type II transmembrane serine protease expressed by cells
      of surface epithelial origin, including epithelial ovarian tumor cells.
      Matriptase cleaves and activates proteins implicated in the progression of
      ovarian cancer and represents a potential prognostic and therapeutic target. The
      aim of this study was to examine the expression of matriptase, and its inhibitor,
      hepatocyte growth factor activator inhibitor-1 (HAI-1), in epithelial ovarian
      cancer and to assign clinicopathological correlations. EXPERIMENTAL DESIGN: We
      have determined by immunohistochemistry the expression of matriptase and HAI-1 in
      54 epithelial ovarian cancers. Statistical analyses of immunohistochemistry
      expression data with clinical outcome and clinicopathological parameters were
      then performed. RESULTS: Of 54 tumors tested, 39 (72%) and 11 (20%) were positive
      for matriptase and for HAI-1, respectively. All HAI-1-positive tumors were also
      matriptase positive. Analysis of clinicopathological parameters demonstrated a
      loss of matriptase associated with stage III/IV tumors as compared with stage
      I/II tumors (P = 0.030). There was also a loss of HAI-1 expression associated
      with stage III/IV tumors (P = 0.039). Of 34 stage I/II tumors, 28 (82%) stained
      positive for matriptase, and 10 (29%) stained positive for HAI-1; 10 (29%) tumors
      showed coexpression. Of 20 stage III/IV tumors, however, 11 stained positive for
      matriptase (55%), only 1 of which coexpressed HAI-1 (P = 0.039). CONCLUSIONS:
      Advanced-stage ovarian tumors that express matriptase are more likely to do so in
      the absence of its inhibitor, HAI-1, indicating that an imbalance in the
      matriptase:HAI-1 ratio could be important in the development of advanced disease.
      Such an imbalance could promote the proteolytic activity of matriptase and,
      consequently, a more invasive phenotype.

PMID- 11948121
TI  - Analysis of chemokines and chemokine receptor expression in ovarian cancer
      ascites.
AB  - PURPOSE: Ascitic disease is a common occurrence in human ovarian cancer, but it
      is unclear how the cellular composition of ascitic fluid is determined. Because
      chemokines can determine host cell infiltration in solid ovarian cancer, we
      assessed CC chemokine protein and CC chemokine receptor expression in ovarian
      cancer ascites. EXPERIMENTAL DESIGN: We used reverse transcription-PCR and RNase
      protection assay to determine CC chemokine and chemokine receptor mRNA expression
      and ELISA to measure CC chemokine protein levels. Flow cytometry was used to
      identify cell populations and their chemokine receptor protein expression.
      RESULTS: mRNA for the CC chemokines CCL2, -3, -4, -5, -8, and -22 was expressed
      in cell isolates from ascites samples, and the corresponding proteins were
      detected in ascitic fluid. mRNA for CC chemokine receptors CCR1, -2a, -2b, -3, 
      4, -5, and -8 was detected in cells from ascites. Fluorescence-activated cell
      sorting analysis showed variable numbers of macrophages and CD3(+) T lymphocytes
      (predominantly CD4(+)) within ovarian cancer ascites. CD14(+) macrophages within
      ascites consistently expressed protein for CCR1, -2, and -5. CCR1 was expressed
      by >60% of all T cells, but more CD4(+) than CD8(+) T cells expressed CCR2 and 
      5. A direct correlation was found between the CCL5 concentration and CD3(+) T
      cell infiltration. CONCLUSIONS: We conclude that there is a complex
      chemokine/chemokine receptor network in ovarian cancer ascites. However,
      associations between chemokine receptor expression, chemokine levels, and cell
      counts were limited.

PMID- 11948122
TI  - Polymorphisms in the promoter region of the neutrophil elastase gene are
      associated with lung cancer development.
AB  - Neutrophil elastase (NE) is a powerful serine protease capable of degrading most
      protein components of the extracellular matrix. We hypothesize that this elastase
      may play a significant role in lung cancer development and tested our hypothesis
      in a study of 348 primary lung cancer cases and 299 controls. Analysis of the
      entire gene using denaturing high performance liquid chromatography identified
      two novel single nucleotide polymorphisms (SNPs) in the promoter region: -903 T
      or G (REP-a) and -741 G or A (REP-b). Allele frequencies of these two SNPs were
      compared between the cases and controls using chi(2) statistics. The estimated
      relative risk in association with the TT at REP-a or the GG at REP-b was measured
      by odds ratio. Individuals with -903TT or -741GG allele had a 2.3 and 1.4 times
      higher risk of developing lung cancer than those with TG or AA+AG alleles,
      respectively. The relative risk for the combined effects of both high-risk
      alleles at REP-a and REP-b, i.e., TT-GG type, was 24.8. Functional association of
      the two markers with cancer risk was examined by luciferase activity of the
      promoter containing different SNPs. We demonstrated a 1.9-fold relative
      luciferase activity in the promoter construct with -903T/-741G (T-G) compared
      with the -903G/-741A (G-A) in A549 human non-small cell lung cancer cells,
      providing evidence that the TT-GG type correlates with a high NE level. In
      conclusion, our findings support an etiological role of NE in lung cancer
      development.

PMID- 11948123
TI  - Infrequent mutation in the BRCA2 gene in esophageal squamous cell carcinoma.
AB  - PURPOSE: Previous studies have shown a high rate of allelic loss in esophageal
      squamous cell carcinoma (ESCC) in the vicinity of the BRCA2 gene. We aimed to
      assess whether the tumor suppressor gene BRCA2 was the inactivation target for
      allelic loss observed on chromosome 13q in ESCC. EXPERIMENTAL DESIGN: We examined
      the entire coding sequence of the BRCA2 gene for mutations using single-strand
      conformation polymorphism analysis and DNA sequencing in 56 ESCC patients from
      Shanxi, China. RESULTS: Eight mutations were identified in 5 patients (9%),
      including 3 with germ-line mutations and 2 with only somatic mutations. However,
      all but 1 of the mutations were missense or silent changes and of unknown
      significance. Evidence for potential biallelic inactivation was seen in only 4
      (7%) cases. CONCLUSIONS: BRCA2 mutations occur in ESCC but are infrequent and of
      unknown consequence. The putative target tumor suppressor gene corresponding to
      the high rate of chromosome 13q allelic loss remains unknown.

PMID- 11948124
TI  - Differential gene expression in human lung adenocarcinomas and squamous cell
      carcinomas.
AB  - PURPOSE: Differential cDNA library screening was performed on 7 human lung
      adenocarcinomas and 7 human lung squamous cell carcinomas and their corresponding
      adjacent normal tissues using a human lung cDNA library constructed from the
      normal bronchoalveolar cells of a 72-year-old male smoker. EXPERIMENTAL DESIGN:
      Of the 2758 clones that were differentially expressed between normal and tumor
      tissues in the preliminary cDNA library screening analysis, 1163 clones were
      confirmed by dot blot, revealing a confirmation rate of >40%. DNA of confirmed
      clones was sequenced and was subjected to GenBank Blast searches. RNA expression
      levels were then individually analyzed by semiquantitative reverse transcription
      PCR. RESULTS: Ninety-two genes/sequences were differentially expressed in
      adenocarcinomas and/or squamous cell carcinomas compared with their corresponding
      normal tissues. Several genes were underexpressed by at least 50% in both tumor
      types such as c-fos, decorin, alpha-2-macroglobulin, platelet endothelial cell
      adhesion molecule 1, EGR1, and fibronectin. Ribosomal protein S3 was
      underexpressed only in squamous cell carcinomas, whereas expression of hepatocyte
      growth factor activator inhibitor type 2, ubiquitin-conjugating enzyme UBC9, and
      clone 333E23 on chromosome Xq21.1 were altered only in adenocarcinomas. Several
      genes discovered recently of which the functions are unknown, such as KIAA0728
      and KIAA0425, were also differentially expressed in both adenocarcinomas and
      squamous cell carcinomas of the lung. CONCLUSIONS: Many of these known and novel
      genes may be involved in human lung tumorigenesis; therefore, additional
      characterization is warranted and will be beneficial to the understanding of this
      deadly disease.

PMID- 11948125
TI  - Bombesin receptor subtypes in human cancers: detection with the universal
      radioligand (125)I-[D-TYR(6), beta-ALA(11), PHE(13), NLE(14)] bombesin(6-14).
AB  - PURPOSE: Bombesin and bombesin receptors have been shown to play a role in
      cancer. Whereas the gastrin-releasing peptide (GRP) receptor is a bombesin
      receptor subtype frequently expressed by tumors, the other three subtypes, the
      neuromedin B (NMB), BB3, and BB4 receptors, have been poorly investigated in
      human tissues. EXPERIMENTAL DESIGN: We investigated 161 human tumors for their
      bombesin receptor subtype expression using in vitro receptor autoradiography with
      the universal bombesin radioligand (125)I-[D-Tyr(6), beta-Ala(11), Phe(13),
      Nle(14)]bombesin(6-14) in displacement experiments with unlabeled GRP, bombesin,
      NMB, and [D-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]bombesin(6-14). The distinct
      rank order of potencies of these analogues for each receptor subtype allows us to
      identify the predominant subtype expressed by each tumor. RESULTS: Twelve of 12
      prostate cancers, 41 of 57 breast cancers, and 5 of 5 gastrinomas expressed
      predominantly GRP receptors; 11 of 24 intestinal, 1 of 26 bronchial, and 1 of 1
      thymic carcinoids had preferentially NMB receptors; 9 of 26 bronchial carcinoids,
      1 large cell neuroendocrine lung carcinoma, and 4 of 9 small cell lung carcinomas
      had preferentially BB3 receptors, whereas 3 of 9 small cell lung carcinomas had
      GRP receptors. Renal cell carcinomas had GRP receptors in 6 of 16 cases and BB3
      receptors in 4 of 16 cases. Finally, 2 of 10 Ewing sarcomas had BB3 receptors. In
      situ hybridization detected BB3 receptor mRNA in neuroendocrine tumors expressing
      the BB3 protein. CONCLUSIONS: This is the first study detecting the proteins of
      BB3, NMB, and GRP receptors in a group of human tumors using differential binding
      techniques. Particularly relevant is the BB3 expression in lung carcinoids and
      other neuroendocrine lung tumors, whereas gastrointestinal carcinoids preferably
      express NMB receptors. These tumors may be targets for diagnostic and
      radiotherapeutic applications of subtype-selective bombesin analogues.

PMID- 11948126
TI  - Increased expression of CD40 ligand on activated T cells of patients with colon
      cancer.
AB  - PURPOSE: Proper function of T lymphocytes is crucial for an effective destruction
      of cancer cells in vivo. Identifying the cell surface molecules on the T cells
      that may be involved in this antitumor response may help to elucidate
      immunological factors influencing the biology of human tumors. EXPERIMENTAL
      DESIGN: Differences in the antigen expression profile of unstimulated and
      stimulated peripheral blood T-lymphocytes from patients with colon cancer and
      from normal controls were determined using flow cytometry. RESULTS: Freshly
      isolated peripheral blood T cells of patients with colon cancer did not differ in
      their phenotype significantly from those of patients with nonmalignant diseases.
      In contrast, in vitro stimulated T cells of patients with colon cancer had a
      significantly increased expression of CD40 ligand (CD40L, CD154) compared with
      activated T cells of the control group; increased CD40L expression was also found
      in the CD4(+)- and CD8(+)-T-cell subpopulations. CONCLUSIONS: The data presented
      support additional studies investigating the role of CD40L in the immune response
      against colon carcinoma.

PMID- 11948127
TI  - Degradation of tenascin-C and activity of matrix metalloproteinase-2 are
      associated with tumor recurrence in early stage non-small cell lung cancer.
AB  - PURPOSE: To find out an effective prognostic factor for early stage non-small
      cell lung cancer (NSCLC), we examined the relationship of the degree of tenascin
      C (TN-C) degradation in relapsed NSCLC tumors with the prognosis of the patients.
      The molecular mechanism of TN-C degradation was also evaluated. EXPERIMENTAL
      DESIGN: In 63 stage-1 NSCLC patients, TN-C protein was analyzed by Western
      blotting, and the activity of matrix metalloproteinase (MMP)-2 was examined by
      gelatin zymography in 23 stage-1 NSCLC patients. RESULTS: Degradation of TN-C was
      detected in 12 of 63 patients. TN-C degradation was detected in 9 of 17 patients
      (52.9%) that showed local and distant cancer recurrences. In short, in 9 of 12
      patients (75%) showing TN-C degradation, lung cancer recurrence was recognized.
      The actual frequency of free-from-recurrence at 4 years was 28.1% in patients
      with tumors showing TN-C degradation, and actual frequency of free-from
      recurrence at 4 years and 10 years was 82.1% and 76.6% in patients without TN-C
      degradation (P < 0.001). In 23 stage-1 NSCLC patients, in tumors with or without
      degraded TN-C, the mean ratio of tumor:normal-tissue of activated MMP-2 was 3.5
      +/- 0.4 or 1.54 +/- 0.4, respectively. Significantly increased activity of MMP-2
      was recognized in tumors showing TN-C degradation (P < 0.001). CONCLUSIONS: These
      results suggest that TN-C degradation is a reliable marker for recurrence
      potential of stage-1 NSCLC and that MMP-2 may be a protease breaking down TN-C in
      lung cancer.

PMID- 11948129
TI  - Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate
      cancer.
AB  - PURPOSE: Whereas the early stage of prostate cancer is marked by excessive
      proliferation, in advanced stages of the disease, a decreased apoptotic death
      rate (increased cell survival) also contributes to net tumor growth. Altered
      regulation of the mitogen-activated protein kinase (MAPK)-regulated cell
      proliferation and Akt-regulated cell survival pathways are suspected causes. In
      this study, we wanted to determine: (a) whether the degree of Akt activation can
      be assessed by immunohistochemical staining of paraffin- embedded human prostate
      cancer biopsies with an antibody to phospho-Akt (Ser473); and (b) whether phospho
      MAPK/Erk1/2 and phospho-Akt expression are altered in prostate cancer.
      EXPERIMENTAL DESIGN: To examine the activation status of MAPK/Erk1/2 and Akt,
      archival paraffin-embedded sections from 74 cases of resected prostate cancer
      were immunostained with antibodies to phospho-MAPK/Erk1/2 (Thr202/ Tyr204) and
      phospho-Akt (Ser473). RESULTS: The staining intensity for phospho-Akt was
      significantly greater in Gleason grades 8-10 (92% of such cases staining
      strongly) compared with prostatic intraepithelial neoplasia and all other grades
      of prostate cancer (only 10% of these cases staining strongly; P < or = 0.001).
      The staining intensity for phospho-MAPK/Erk, on the other hand, was significantly
      greater for normal, hyperplastic, and prostatic intraepithelial neoplasia lesions
      but declined with disease progression, reaching its lowest level of expression in
      high Gleason grades 8-10 (P < 0.0001). CONCLUSION: The activation state of the
      cell survival protein Akt can be analyzed in human prostate cancer by
      immunohistochemical staining of paraffin-embedded tissue with a phospho-specific
      Akt (Ser473) antibody. Advanced disease is accompanied by activation of Akt and
      inactivation of Erk.

PMID- 11948128
TI  - Expressions of cyclooxygenase-2 and prostaglandin E-receptors in carcinoma of the
      gallbladder: crucial role of arachidonate metabolism in tumor growth and
      progression.
AB  - An association of gallbladder carcinoma with cholelithiasis suggests that chronic
      inflammation may modulate tumorigenesis and/or progression of the carcinoma. An
      enhanced expression of cyclooxygenase-2 (COX-2) is observed frequently in
      advanced carcinomas of gastrointestinal tracts, which in turn suggests that
      potentiated arachidonate metabolism may play a crucial role in tumor biology. In
      the present study, the expression levels of COX-2 and prostaglandin E receptor
      subtypes were determined in 16 cases of gallbladder carcinomas of different
      depths of invasion (pT(1) 3, pT(2) 2, pT(3) 4, and pT(4) 7) to determine the role
      of arachidonate metabolism in tumor growth and progression. The mRNA levels of
      COX-2 were increased significantly in pT(3) and pT(4) carcinomas compared with
      the levels in pT(1) and pT(2) carcinomas. Immunohistochemistry and in situ
      hybridization revealed the existence of COX-2 mRNA and protein in both the
      cancerous epithelia and adjacent stroma of pT(1)-pT(4) carcinomas. Only in pT(3)
      and pT(4) carcinomas was intense expression of COX-2 observed in the adjacent
      stroma. The tissue concentration of PGE(2) was significantly increased in pT(3)
      and pT(4) carcinomas. The mRNAs of PGE receptor subtypes EP(2), EP(3), and EP(4)
      were amplified in pT(1)-pT(4) gallbladder carcinomas, in which their mRNAs and
      EP(4) protein were expressed mostly in the cancerous epithelia. Treatment with a
      specific EP(4) agonist, as well as PGE(2) but not EP(2) and EP(3) agonists, up
      regulated the expression of c-fos, an induced growth response gene, and increased
      colony formation. In advanced gallbladder carcinoma, enhanced expression of COX-2
      is observed in the adjacent stroma rather than in the cancerous epithelia, and
      the stroma is a potent source of PG synthesis. In epithelial-stromal
      interactions, the increased PGE(2) synthesis in the adjacent stroma and its
      biological effect via EP(4) on the carcinoma cells may contribute to tumor growth
      and progression of gallbladder carcinoma.

PMID- 11948130
TI  - Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery.
AB  - PURPOSE: Anti-HER2 immunoliposomes combine the tumor-targeting of certain anti
      HER2 monoclonal antibodies (MAbs) with the pharmacokinetic and drug delivery
      capabilities of sterically stabilized liposomes. We previously showed that anti
      HER2 immunoliposomes bind efficiently to and internalize in HER2-overexpressing
      cells in vitro, resulting in intracellular drug delivery. EXPERIMENTAL DESIGN:
      Here we describe the pharmacokinetics and therapeutic efficacy of anti-HER2
      immunoliposomes containing doxorubicin (dox) in a series of animal models.
      RESULTS: Immunoliposomes displayed long circulation that was identical to that of
      sterically stabilized liposomes in single- and multiple-dose studies in normal
      rats. Anti-HER2 immunoliposome-dox produced marked therapeutic results in four
      different HER2-overexpressing tumor xenograft models, including growth
      inhibition, regression, and cures. These results demonstrated that encapsulation
      of dox in anti-HER2 immunoliposomes greatly increased its therapeutic index, both
      by increasing antitumor efficacy and by reducing systemic toxicity.
      Immunoliposome-dox was significantly superior to all other treatment conditions
      tested, including free dox, liposomal dox, and anti-HER2 MAb (trastuzumab). When
      compared with liposomal dox in eight separate therapy studies in HER2
      overexpressing models, immunoliposome delivery produced significantly superior
      antitumor efficacy in each study (P < 0.0001 to 0.04). Anti-HER2 immunoliposome
      dox containing either recombinant human MAb HER2-Fab' or scFv C6.5 yielded
      comparable therapeutic efficacy. Cure rates for immunoliposome-dox reached 50%
      (11 of 21) with optimized immunoliposomes and Matrigel-free tumors and overall
      was 16% (18 of 115) versus no cures (0 of 124) with free dox or liposomal dox.
      Finally, anti-HER2 immunoliposome-dox was also superior to combinations
      consisting of free MAb plus free dox or free MAb plus liposomal dox. CONCLUSIONS:
      Anti-HER2 immunoliposomes produced enhanced antitumor efficacy via targeted
      delivery.

PMID- 11948132
TI  - Enhancement of DNA ligase I level by gemcitabine in human cancer cells.
AB  - PURPOSE: DNA ligase I is an essential enzyme for completing DNA replication and
      DNA repair by ligating Okazaki fragments and by joining single-strand breaks
      formed either directly by DNA-damaging agents or indirectly by DNA repair
      enzymes, respectively. In this study, we examined whether the DNA ligase I level
      could be modulated in human tumor cell lines by treatment with gemcitabine (2',
      2'-difluoro-2'-deoxycytidine), which is a nucleoside analogue of cytidine with
      proven antitumor activity against a broad spectrum of human cancers in clinical
      studies. EXPERIMENTAL DESIGN: To determine the effect of gemcitabine on DNA
      ligase I expression, Western blot analysis was used to measure the DNA ligase I
      levels in MiaPaCa, NGP, and SK-N-BE cells treated with different concentrations
      of gemcitabine and harvested at different time intervals. Cell cycle analysis was
      also performed to determine the underlying mechanism of DNA ligase I level
      enhancement in response to gemcitabine. In addition, other agents that share the
      same mechanism of action with gemcitabine were used to elucidate further details.
      RESULTS: When different types of tumor cell lines, including MiaPaCa, NGP, and SK
      N-BE, were treated with gemcitabine, the level of DNA ligase I increased
      severalfold despite significant cell growth inhibition. In contrast, other DNA
      ligases (III and IV) either remained unchanged or decreased with treatment. Cell
      cycle analysis showed that arrest in S-phase corresponded to an increase of DNA
      ligase I levels in gemcitabine treated cells. Other agents, such as 1-beta-D
      arabinofuranosylcytosine and hydroxyurea, which partly share mechanisms of action
      with gemcitabine by targeting DNA polymerases and ribonucleotide reductase,
      respectively, also caused an increase of DNA ligase I levels. However, 5
      fluorouracil, which predominantly targets thymidylate synthase, did not cause an
      increase of DNA ligase I level. CONCLUSIONS: Our results suggest that an arrest
      of DNA replication caused by gemcitabine treatment through incorporation of
      gemcitabine triphosphate into replicating DNA and inhibition of ribonucleotide
      reductase would trigger an increase in DNA ligase I levels in cancer cells. The
      elevated presence of DNA ligase I in S-phase-arrested cells leads us to speculate
      that DNA ligase I might have an important role in repairing DNA damage caused by
      stalled replication forks.

PMID- 11948131
TI  - Antiangiogenic and antitumor activity of IDN 5390, a new taxane derivative.
AB  - PURPOSE: We previously reported that paclitaxel, a microtubule-stabilizing drug,
      inhibited angiogenesis, mainly by inhibiting endothelial cell motility (D.
      Belotti et al., Clin. Cancer Res., 2: 1843-1849, 1996). The aim of this study was
      to select a taxane with little cytotoxicity but with antimotility and hence
      antiangiogenic activity. EXPERIMENTAL DESIGN: Different taxanes, seco
      derivatives, and 14-beta-hydroxy-10-deacetyl baccatin III derivatives were tested
      for their effects on the proliferation and motility of human umbilical vein
      endothelial cells. The antiangiogenic and antineoplastic activities of the
      compound selected from this screening were further investigated in experimental
      models in vitro and in vivo. RESULTS: From the screening of different taxanes, we
      selected IDN 5390, a seco derivative that showed potent antimotility activity and
      less cytotoxicity than paclitaxel. In comparable experimental conditions, IDN
      5390 inhibited endothelial cell migration without affecting proliferation. This
      compound dose-dependently inhibited the capacity of human umbilical vein
      endothelial cells plated on Matrigel to organize into a network of cords. In
      vivo, IDN 5390 significantly inhibited fibroblast growth factor-2-induced
      angiogenesis in Matrigel implants. Daily treatment with IDN 5390 in mice bearing
      established lung micrometastases from the B16BL6 murine melanoma caused a
      reduction in the size of metastases. Finally, IDN 5390 slowed the s.c. growth of
      the paclitaxel-resistant human ovarian carcinoma, 1A9/PTX22, xenografted in nude
      mice. CONCLUSIONS: The seco derivative IDN 5390 might represent the prototype of
      a new class of taxane derivatives with antiangiogenic properties.

PMID- 11948133
TI  - A novel design of targeted endocrine and cytokine therapy for breast cancer.
AB  - The aim of this study is to combine endocrine therapy [human prolactin (hPRL)
      antagonist, G129R] and immune therapy [interleukin 2 (IL2)] in the design of a
      fusion protein, G129R-IL2, to treat human breast cancer. This novel approach uses
      the specific interaction between the G129R and hPRL receptors (PRLRs), thus
      directly targeting the fusion protein to the malignant breast tissues that have
      previously been shown to contain high levels of PRLR. The localized bifunctional
      fusion protein is designed to block signal transduction induced by hPRL as well
      as to activate T lymphocytes near the tumor site. A bacterial expression system
      was used to produce G129R-IL2 fusion protein that maintained both G129R and IL2
      activities as demonstrated by cell-based assays such as signal transducer(s) and
      activator(s) of transcription (STAT)5 phosphorylation, breast cancer cell
      proliferation, and T-cell proliferation. The antitumor activities of G129R-IL2
      were demonstrated in vivo using a syngeneic model system with BALB/c mice and
      EMT6-hPRLR breast cancer cells. After daily injection (i.p.) of G129R-IL2 (100
      microg/mouse) for 18 days, the tumor growth in the G129R-IL2-treated group was
      only one-third the size as compared with that of the control group. The growth
      rate in the G129R-IL2-treated group is also significantly slower than that of the
      group treated with G129R alone (200 microg/mouse/day). We hope that this novel
      bifunctional protein will contribute significantly to human breast cancer
      therapy.

PMID- 11948134
TI  - Enhanced growth inhibition by combination differentiation therapy with ligands of
      peroxisome proliferator-activated receptor-gamma and inhibitors of histone
      deacetylase in adenocarcinoma of the lung.
AB  - PURPOSE: Histone deacetylase (HDAC) inhibitors and ligands of the peroxisome
      proliferator-activated receptor gamma (PPARgamma) have been shown previously to
      induce growth arrest and differentiation in a variety of cancer cell lines. The
      purpose of this study was to determine whether HDAC inhibitors function similarly
      in non-small cell lung cancer (NSCLC) and whether combination treatment with HDAC
      inhibitors and PPARgamma ligands is more efficacious than either agent alone.
      EXPERIMENTAL DESIGN AND RESULTS: Nanomolar concentrations of trichostatin A
      induced growth arrest in five of seven NSCLC cell lines, whereas sodium
      phenylbutyrate (PB) was markedly less potent. In adenocarcinomas, trichostatin A
      up-regulated general differentiation markers (gelsolin, Mad, and p21/WAF1) and
      down-regulated markers of the type II pneumocyte progenitor cell lineage (MUC1
      and SP-A), indicative of a more mature phenotype. PB had a similar effect.
      Simultaneous treatment with a PPARgamma ligand and PB enhanced the growth
      inhibition in adenocarcinomas but not in nonadenocarcinomas. Growth arrest was
      accompanied by markedly decreased cyclin D1 expression but not enhanced
      differentiation. CONCLUSIONS: The present study demonstrates potent growth
      inhibitory and differentiation-inducing activity of HDAC inhibitors in NSCLC and
      suggests that combination differentiation therapy should be explored further for
      the treatment of lung adenocarcinomas.

PMID- 11948136
TI  - Radiation-induced increase in invasive potential of human pancreatic cancer cells
      and its blockade by a matrix metalloproteinase inhibitor, CGS27023.
AB  - PURPOSE: Radiotherapy remains a major therapeutic option for patients with
      advanced pancreatic cancer. Nevertheless, the effects of irradiation on malignant
      biological behaviors (e.g., migration and invasion of cancer cells) have yet to
      be clarified. Thus, we conducted an in vitro study to investigate the radiation
      induced alterations around cell migration and invasion capacity. EXPERIMENT
      DESIGN: Three cell lines from human pancreatic cancer were included in the study.
      gamma-radiation was used for irradiation treatment. Cell migration and invasion
      ability were evaluated by Transwell migration assay and Matrigel invasion assay.
      The activity of MMP-2 and 9, and expression of urokinase-type plasminogen
      activator were investigated with gelatin zymography and immunoblot, respectively.
      RESULTS: Irradiation enhances invasive potential in some pancreatic cancer cells,
      whereas it significantly inhibits cell proliferation and migration. This hitherto
      unknown biological effect of irradiation involves enhanced matrix
      metalloproteinase (MMP)-2 activity. Consequently, simultaneous administration of
      an MMP inhibitor, CGS27023A, suppresses the radiation-enhanced invasion through
      blockade of transition of MMP-2 from latent type to active type. CONCLUSION:
      Because radiation may increase invasion ability through activating MMP
      proteolytic system, simultaneous administration of the MMP inhibitor during
      radiotherapy could be a potent adjuvant therapeutic approach to improve the
      efficacy of radiotherapy for pancreatic cancer.

PMID- 11948135
TI  - Tumor-specific regulation of angiogenic growth factors and their receptors during
      recovery from cytotoxic therapy.
AB  - After cytotoxic treatment, up-regulation of vascular growth factors and their
      receptors may be crucial for tumor relapse or progression. To determine how
      cytotoxic therapy (radioimmunotherapy) alters expression of angiogenic growth
      factors and receptors, athymic mice bearing LoVo, GW-39, HT-29, or Calu3 human
      tumor xenografts were treated with one dose (240 microCi) of (131)I-MN-14 anti
      CEA IgG or (295 microCi) (131)I-RS-7-3G11 anti-EGP-1 IgG. Tumors removed at 1
      week intervals up to week 6 were probed by immunohistochemistry (n = 3-11
      samples) for vascular endothelial growth factor (VEGF), placental growth factor
      (PlGF), flk-1 and flt-1, angiopoietin-1 and -2, and Tie-1 and -2. Tumor extracts
      were also assayed for VEGF by immunoblot and for PlGF by comparative reverse
      transcription-PCR. During weeks 2-5 after radioimmunotherapy, significantly up
      regulated tumor cell VEGF was only detected in HT-29 (immunohistochemistry; 2
      fold; week 4; P < 0.05). The increased VEGF of HT-29 was paralleled by a 2-fold
      (week 4) rise in VEGF receptor flk-1 on vessels as well as increased ang-2/Tie-2.
      HT-29, GW-39, and Calu-3 increased tumor cell expression of PlGF by week 2 (HT-29
      and Calu-3, P < 0.05). In Calu-3, PlGF mRNA increased 8-fold at week 5. PlGF was
      detected in hypoxic areas at week 2. Vascular expression of orphan receptor Tie-1
      increased in all four of the tumors by week 2 (LoVo, GW-39, and Calu-3, P <
      0.05). Regulation of angiogenic factors and angiogenesis after tumoricidal
      therapy may be tumor-specific. Antiangiogenic therapy may require a tumor
      specific combination of inhibitors for PlGF, the angiopoietins, or their
      receptors, in addition to VEGF/flk-1.

PMID- 11948137
TI  - Akt inactivation is a key event in indole-3-carbinol-induced apoptosis in PC-3
      cells.
AB  - Indole-3-carbinol (I3C) is a bioactive compound present in Brassica vegetables
      that shows an antitumor activity in experimental animals and inhibits the growth
      of human cancer cells in vitro. In recent years, studies on prostate cancer (PCa)
      chemoprevention have been intensified, because there is a long latency for the
      development of clinical PCa, which makes the PCa a better target for
      chemoprevention. We have shown previously that I3C induces cell growth inhibition
      by G(1) cell cycle arrest and induces apoptosis in a dose- and time-dependent
      manner in PC-3 PCa cells; however, the mechanism(s) by which I3C induces
      apoptosis in PC-3 cells is still not clear. A cell survival pathway involving
      phosphatidylinositol 3'-kinase (PI3K) and Akt is known to play an important role
      in inhibiting apoptosis in response to growth factor signaling, which prompted us
      to investigate whether this pathway plays any role in I3C-induced apoptosis in
      PCa cells. Here we report that I3C inhibits the phosphorylation and subsequent
      activation of Akt kinase. In addition, I3C abrogated epidermal growth factor
      (EGF)-induced activation of Akt in PC-3 cells. Western blot analyses of EGF
      receptor showed that I3C down-regulates the EGF receptor levels and its
      autophosphorylation. This was also accompanied by the inhibition of EGF-induced
      phosphorylation of PI3K by I3C treatment. Furthermore, the known downstream
      modulators of the Akt/PI3K cell survival pathway, Bcl-x(L), and BAD proteins
      showed decreased expression after I3C treatment. From these results, we conclude
      that I3C-induced apoptosis is partly mediated by the inhibition of Akt
      activation, resulting in the alterations in the downstream regulatory molecules
      of Akt activation in PC-3 cells. However, further in-depth investigation is
      needed to establish a cause-and-effect relationship between Akt pathway and I3C
      effect.

PMID- 11948138
TI  - Influence of Cremophor El on the bioavailability of intraperitoneal paclitaxel.
AB  - It has been hypothesized that the paclitaxel vehicle Cremophor EL (CrEL) is
      responsible for nonlinear drug disposition by micellar entrapment. To gain
      further insight into the role of CrEL in taxane pharmacology, we studied the
      pharmacokinetics of paclitaxel in the presence and absence of CrEL after i.p. and
      i.v. dosing. Patients received an i.p. tracer dose of [G-(3)H]paclitaxel in
      ethanol without CrEL (100 microCi diluted further in isotonic saline) on day 1,
      i.p. paclitaxel formulated in CrEL (Taxol; 125 mg/m(2)) on day 4, an i.v. tracer
      of [G-(3)H]paclitaxel on day 22, and i.v. Taxol (175 mg/m(2)) on day 24. Four
      patients (age range, 54-74 years) were studied, and serial plasma samples up to
      72 h were obtained and analyzed for total radioactivity, paclitaxel, and CrEL. In
      the presence of CrEL, i.v. paclitaxel clearance was 10.2 +/- 3.76 liters/h/m(2)
      (mean +/- SD), consistent with previous findings. The terminal disposition half
      life was substantially prolonged after i.p. dosing (17.0 +/- 11.3 versus 28.7 +/-
      8.72 h), as was the mean residence time (7.28 +/- 2.76 versus 40.7 +/- 13.8 h).
      The bioavailability of paclitaxel was 31.4 +/- 5.18%, indicating insignificant
      systemic concentrations after i.p. treatment. CrEL levels were undetectable after
      i.p. dosing (<0.05 microl/ml), whereas after i.v. dosing, the mean clearance was
      159 +/- 58.4 ml/h/m(2), in line with earlier observations. In the absence of
      CrEL, the bioavailability and systemic concentrations of i.p. paclitaxel were
      significantly increased. This finding is consistent with the postulated concept
      that CrEL is largely responsible for the pharmacokinetic advantage for peritoneal
      cavity exposure to total paclitaxel compared with systemic delivery.

PMID- 11948139
TI  - The antiangiogenic agent neovastat (AE-941) inhibits vascular endothelial growth
      factor-mediated biological effects.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is a potent regulator of
      angiogenesis, which exerts direct effects on vascular endothelial cells,
      including endothelial cell proliferation and survival, tubulogenesis, and
      vascular permeability. In this study, we examined whether Neovastat, a naturally
      occurring multifunctional antiangiogenic drug, could inhibit the endothelial cell
      response to VEGF stimulation. RESULTS: We demonstrated that Neovastat was able to
      block the VEGF-dependent microvessel sprouting from Matrigel-embedded rat aortic
      rings, and it also blocked the VEGF-induced endothelial cell tubulogenesis in
      vitro. In vivo studies showed that Neovastat was able to specifically inhibit
      VEGF-induced plasma extravasation in numerous tissues, including pancreas and
      skin. The mechanism of action of Neovastat on VEGF-mediated effects was also
      evaluated at the molecular level. Neovastat was shown to compete against the
      binding of VEGF to its receptor in endothelial cells and significantly inhibited
      the VEGF-dependent tyrosine phosphorylation of VEGF receptor-2, whereas it had no
      significant effect on VEGF receptor-1 activity. Moreover, the inhibition of
      receptor phosphorylation was correlated with a marked decrease in the ability of
      VEGF to induce pERK activation. Neovastat does not compete against the binding of
      basic fibroblast growth factor, indicating a preferential inhibitory effect on
      the VEGF receptor. CONCLUSIONS: Because Neovastat was shown previously to inhibit
      metalloproteinase activities, these results suggest that Neovastat is able to
      target multiple steps in tumor neovascularization, further emphasizing its use as
      a pleiotropic, multifunctional antiangiogenic drug.

PMID- 11948140
TI  - Luteinizing hormone-releasing hormone agonist limits DU-145 prostate cancer
      growth by attenuating epidermal growth factor receptor signaling.
AB  - PURPOSE: Advanced prostate cancer is treated initially by central suppression of
      androgen production by luteinizing hormone-releasing hormone (LHRH) agonists.
      Intriguingly, even hormone-independent cancers often show some, if only slight,
      growth retardation when these agonists are delivered in pharmacological doses.
      Previous studies have shown in cell lines and animal xenograft models that
      activation of peripheral LHRH receptors on prostate carcinoma cells lead to
      growth suppression. In parallel, there is a decrease of epidermal growth factor
      receptors (EGFRs) and activity. Because autocrine EGFR stimulation exists in
      most, if not all, prostate carcinomas and is required for cell proliferation, we
      asked whether LHRH signaling cross-attenuated EGFR to limit tumor growth. One
      possible mechanism was suggested by LHRH receptors triggering phospholipase-C
      (PLC) to activate protein kinase C (PKC) because PKC activation limits EGFR
      tyrosine kinase activity by phosphorylating EGFR at threonine 654. EXPERIMENTAL
      DESIGN: To determine the role of this cross-attenuation mechanism, we mutated the
      threonine 654 amino acid to an alanine (A654) to abrogate this inhibition. DU-145
      cells stably expressing wild-type and A654 EGFR were grown as xenografts in the
      s.c. space of athymic mice. RESULTS: DU-145 cells, overexpressing wild-type EGFR,
      formed tumors in athymic mice that were inhibitable by goserelin acetate
      (Zoladex). Tumors expressing the A654 EGFR were resistant to this growth
      inhibition. These results paralleled in vitro studies in which goserelin acetate
      blocked proliferation of the WT DU-145 but not A654 DU-145 cells. CONCLUSIONS:
      These data support the model of LHRH agonists preventing EGFR-mediated tumor
      growth through a PKC pathway. This suggests new targets of modulatory
      intervention to limit the growth of androgen-independent prostate carcinomas.

PMID- 11948142
TI  - Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in
      mice.
AB  - PURPOSE: The tumor suppressor gene p16INK4A is inactivated frequently in a large
      number of human cancers, and many investigators have attempted to restore the
      function of p16 using the p16 wild-type gene and viral vectors. In this study, we
      treated the tumor-bearing animals with the p16-derived synthetic peptide coupled
      with the Antennapedia carrier sequence, which we designated as Trojan p16
      peptide. EXPERIMENTAL DESIGN: Injections (i.p.) of the Trojan p16 peptide (100
      microg/mouse/day) were given for 3 weeks in the AsPC-1 and BxPC-3 s.c. tumor
      models. Tumor growth, histopathology, and TUNEL staining of the tumor and
      toxicity of the animals were evaluated. To examine its influence on the survival
      of tumor-bearing mice, Trojan p16 was administered in the AsPC-1 peritoneal
      dissemination model. RESULTS: In the AsPC-1 s.c. tumor model, a significant
      growth inhibition was obtained by the Trojan p16 treatment when compared with the
      three control treatments, i.e., vehicle, unconjugated form of p16, or Trojan
      peptide alone. Tumor growth inhibition was almost complete in the BxPC-3 tumor, a
      relatively slow growing tumor. Neither hematological cytotoxicity or body weight
      loss were observed. Histopathology of the BxPC-3 s.c. tumor in the Trojan p16
      treatment group revealed marked vacuole formation and apoptotic death of cancer
      cells. In the AsPC-1 peritoneal dissemination model, the survival curve of mice
      treated with Trojan p16 was significantly longer than that of control.
      CONCLUSIONS: These results provide evidence that the Trojan p16 peptide system, a
      gene-oriented peptide coupled with a peptide vector, functions for experimental
      pancreatic cancer therapy.

PMID- 11948141
TI  - Inhibition of tumorigenicity and metastasis of human bladder cancer growing in
      athymic mice by interferon-beta gene therapy results partially from various
      antiangiogenic effects including endothelial cell apoptosis.
AB  - We determined whether the IFN-beta gene could suppress angiogenesis, tumor
      growth, and metastasis of human bladder transitional cell carcinoma. The highly
      tumorigenic and metastatic 253J B-V(R) human bladder transitional cell carcinoma
      (TCC) cell line (resistant to the antiproliferative effects of IFN-beta) was
      infected in vitro with adenoviral beta-galactosidase (Ad-LacZ), murine adenoviral
      IFN-beta (Ad-mIFN-beta), or human adenoviral IFN-beta (Ad-hIFN-beta) and
      implanted into the bladders of athymic nude mice. Ad-mIFN-beta and Ad-hIFN-beta
      were used because of the species specificity of IFN-beta. The transient
      production of mIFN-beta and hIFN-beta from the infected 253JB-V(R) tumor cells
      significantly inhibited tumorigenicity and spontaneous lymph node metastasis.
      Subsequently, the 253J B-V(R) cells were implanted into the subcutis of athymic
      nude mice, and established tumors were treated by direct intratumoral injection
      with Ad-mIFN-beta, Ad-hIFN-beta, Ad-LacZ, or PBS. By in situ hybridization (ISH)
      and immunohistochemical analysis (IHC), expression of hIFN-beta and mIFN-beta
      mRNA and protein within the tumors was demonstrated after Ad-hIFN-beta and Ad
      mIFN-beta gene therapy, respectively. The therapy also induced necrosis in both
      the Ad-mIFN-beta- and Ad-hIFN-beta-treated tumors. IHC revealed decreased tumor
      cell proliferation and the sequestration of activated macrophages within the
      tumors after Ad-mIFN-beta therapy. In addition, the expression of the
      proangiogenic factors bFGF, and MMP-9 protein (by IHC) was significantly down
      regulated by Ad-hIFN-beta gene therapy. Double-immunofluorescent IHC for terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) and
      CD-31 demonstrated tumor and endothelial cell apoptosis in those tumors treated
      with Ad-hIFN-beta gene therapy. Tumor-induced angiogenesis, as determined by the
      microvessel density, was decreased in tumors treated with both Ad-mIFN-beta and
      Ad-hIFN-beta. These data suggest that the inhibition of tumorigenicity and the
      metastasis of the 253J B-V(R) cells after infection with Ad-IFN-beta is caused by
      the inhibition of angiogenesis and the activation of host effector cells.

PMID- 11948143
TI  - Bcl-2 antisense oligonucleotides are effective against systemic but not central
      nervous system disease in severe combined immunodeficient mice bearing human
      t(14;18) follicular lymphoma.
AB  - The t(14;18) is present in 85-90% of follicular lymphomas. It results in
      overexpression of the Bcl-2 protein, which inhibits apoptosis and plays a role in
      lymphomagenesis. Bcl-2 antisense oligonucleotides (ODNs) down-regulate Bcl-2
      expression and inhibit growth of the follicular lymphoma cell line WSU-FSCCL. In
      this study, we have established a human lymphoma xenograft model in severe
      combined immunodeficient (SCID) mice using the WSU-FSCCL cell line. s.c., i.v.,
      or i.p. injection of WSU-FSCCL cells into SCID mice results in the development of
      disseminated tumors, with the liver, spleen, bone marrow, and lymph nodes as
      major sites of disease. Tumors were fatal in 7-14 weeks, depending on cell
      inoculum and route of administration. Immunohistochemistry, flow cytometry, and
      cytogenetic analysis confirmed the human B-cell origin of tumor cells in the
      xenograft. Phosphorothioate ODNs against the translation initiation site of bcl-2
      mRNA in the antisense and mismatched antisense sequences were administered i.v.
      or i.p. to the xenograft models three times a week for 2 weeks, starting on day 7
      after tumor injections. Antisense-treated animals had significantly longer
      survival (mean, 11.6 weeks) compared with 7.6 weeks for the control group and 7.5
      weeks for the mismatched antisense-treated animals (P = 0.002 and 0.004,
      respectively). More significantly, a pathological examination showed no tumor in
      the liver, spleen, or bone marrow of the antisense group. However, subsequent
      experiments showed that the central nervous system was involved, causing mice to
      die although other sites were disease free. We conclude that bcl-2 antisense ODN
      therapy is effective against systemic FSCCL disease in SCID mice xenografts;
      however, it does not prevent disease dissemination into the central nervous
      system causing animal death.

PMID- 11948144
TI  - Acid production in glycolysis-impaired tumors provides new insights into tumor
      metabolism.
AB  - PURPOSE: Low extracellular pH is a hallmark of solid tumors. It has long been
      thought that this acidity is mainly attributable to the production of lactic
      acid. In this study, we tested the hypothesis that lactate is not the only source
      of acidification in solid tumors and explored the potential mechanisms underlying
      these often-observed high rates of acid production. EXPERIMENTAL DESIGN: We
      compared the metabolic profiles of glycolysis-impaired (phosphoglucose isomerase
      deficient) and parental cells in both in vitro and two in vivo models (dorsal
      skinfold chamber and Gullino chamber). RESULTS: We demonstrated that CO(2), in
      addition to lactic acid, was a significant source of acidity in tumors. We also
      found evidence supporting the hypothesis that tumor cells rely on glutaminolysis
      for energy production and that the pentose phosphate pathway is highly active
      within tumor cells. Our results also suggest that the tricarboxylic acid cycle is
      saturable and that different metabolic pathways are activated to provide for
      energy production and biosynthesis. CONCLUSIONS: These results are consistent
      with the paradigm that tumor metabolism is determined mainly by substrate
      availability and not by the metabolic demand of tumor cells per se. In
      particular, it appears that the local glucose and oxygen availabilities each
      independently affect tumor acidity. These findings have significant implications
      for cancer treatment.

PMID- 11948145
TI  - Identification of the Clostridium perfringens genes involved in the adaptive
      response to oxidative stress.
AB  - Clostridium perfringens is a ubiquitous gram-positive pathogen that is present in
      the air, soil, animals, and humans. Although C. perfringens is strictly
      anaerobic, vegetative and stationary cells can survive in a growth-arrested stage
      in the presence of oxygen and/or low concentrations of superoxide and hydroxyl
      radicals. Indeed, it possesses an adaptive response to oxidative stress, which
      can be activated in both aerobic and anaerobic conditions. To identify the genes
      involved in this oxidative stress response, C. perfringens strain 13 mutants were
      generated by Tn916 insertional mutagenesis and screened for resistance or
      sensitivity to various oxidative stresses. Three of the 12 sensitive mutants
      examined harbored an independently inserted single copy of the transposon in the
      same operon as two genes orthologous to the ydaD and ycdF genes of Bacillus
      subtilis, which encode a putative NADPH dehydrogenase. Complementation
      experiments and knockout experiments demonstrated that these genes are both
      required for efficient resistance to oxidative stress in C. perfringens and are
      probably responsible for the production of NADPH, which is required for
      maintenance of the intracellular redox balance in growth-arrested cells. Other
      Tn916 disrupted genes were also shown to play important roles in the oxidative
      stress response. This is the first time that some of these genes (e.g., a gene
      encoding an ATP-dependent RNA helicase, the beta-glucuronidase gene, and the gene
      encoding the atypical iron sulfur prismane protein) have been shown to be
      involved in the oxidative response.

PMID- 11948146
TI  - Whole-genome analysis of genes regulated by the Bacillus subtilis competence
      transcription factor ComK.
AB  - The Bacillus subtilis competence transcription factor ComK is required for
      establishment of competence for genetic transformation. In an attempt to study
      the ComK factor further, we explored the genes regulated by ComK using the DNA
      microarray technique. In addition to the genes known to be dependent on ComK for
      expression, we found many genes or operons whose ComK dependence was not known
      previously. Among these genes, we confirmed the ComK dependence of 16 genes by
      using lacZ fusions, and three genes were partially dependent on ComK.
      Transformation efficiency was significantly reduced in an smf disruption mutant,
      although disruption of the other ComK-dependent genes did not result in
      significant decreases in transformation efficiency. Nucleotide sequences similar
      to that of the ComK box were found for most of the newly discovered genes
      regulated by ComK.

PMID- 11948147
TI  - Population heterogeneity of Salmonella enterica serotype Typhimurium resulting
      from phase variation of the lpf operon in vitro and in vivo.
AB  - The lpf fimbrial operon oscillates between phase ON and phase OFF expression
      states, thereby generating heterogeneity within S. enterica serotype Typhimurium
      populations with regard to expression of long polar fimbrial antigens. To
      determine whether the proportion of lpf phase variants changes with growth
      conditions, the lpf phase ON content of cultures was determined after in vitro
      and in vivo passage. After passage in Luria-Bertani (LB) broth for 120
      generations, 96% of cells in a serotype Typhimurium culture carried the lpf
      operon in the phase ON expression state, regardless of the phase ON/OFF ratio in
      the inoculum. In contrast, a culture passaged on LB agar plates for 500
      generations contained approximately 2% lpf phase ON cells. Differences in the lpf
      phase ON content of cultures passaged in broth and on plates were not caused by
      an outgrowth of lpf phase ON or lpf phase OFF cells, since deletion of lpf
      biosynthesis genes did not alter the phase ON/OFF ratio attained after passage.
      Instead, growth in LB broth resulted in a eightfold increase in the phase OFF-to
      ON transition frequency and a decrease of the lpf phase ON-to-OFF transition
      frequency by a factor of 150 compared to growth on LB agar plates. After
      infection of naive CBA/J mice with an lpf phase ON culture of serotype
      Typhimurium, the proportion of lpf phase ON cells continuously decreased over
      time, regardless of whether the strain carried intact fimbrial biosynthesis
      genes. These data suggest that elaboration of fimbriae does not have a major
      influence on the population heterogeneity produced by phase variation of the lpf
      operon in naive mice.

PMID- 11948148
TI  - Critical regions of secM that control its translation and secretion and promote
      secretion-specific secA regulation.
AB  - SecA is an essential ATP-driven motor protein that binds to presecretory or
      membrane proteins and the translocon and promotes the translocation or membrane
      integration of these proteins. secA is subject to a protein secretion-specific
      form of regulation, whereby its translation is elevated during secretion-limiting
      conditions. A novel mechanism that promotes this regulation involves
      translational pausing within the gene upstream of secA, secM. The secM
      translational pause prevents formation of an RNA helix that normally blocks secA
      translational initiation. The duration of this pause is controlled by the rate of
      secretion of nascent SecM, which in turn depends on its signal peptide and a
      functional translocon. We characterized the atypical secM signal peptide and
      found that mutations within the amino-terminal region specifically affect the
      secM translational pause and secA regulation, while mutations in the hydrophobic
      core region affect SecM secretion as well as translational pausing and secA
      regulation. In addition, mutational analysis of the 3' end of secM allowed us to
      identify a conserved region that is required to promote the translational pause
      that appears to be operative at the peptide level. Together, our results provide
      direct support for the secM translational pause model of secA regulation, and
      they pinpoint key sequences within secM that promote this important regulatory
      system.

PMID- 11948149
TI  - Mutations in Flavobacterium johnsoniae gldF and gldG disrupt gliding motility and
      interfere with membrane localization of GldA.
AB  - Flavobacterium johnsoniae moves rapidly over surfaces by a process known as
      gliding motility. The mechanism of this form of motility is not known. Four genes
      that are required for F. johnsoniae gliding motility, gldA, gldB, gldD, and ftsX,
      have recently been described. GldA is similar to the ATP-hydrolyzing components
      of ATP binding cassette (ABC) transporters. Tn4351 mutagenesis was used to
      identify two additional genes, gldF and gldG, that are required for cell
      movement. gldF and gldG appear to constitute an operon, and a Tn4351 insertion in
      gldF was polar on gldG. pMK314, which carries the entire gldFG region, restored
      motility to each of the gldF and gldG mutants. pMK321, which expresses GldG but
      not GldF, restored motility to each of the gldG mutants but did not complement
      the gldF mutant. GldF has six putative membrane-spanning segments and is similar
      in sequence to channel-forming components of ABC transporters. GldG is similar to
      putative accessory proteins of ABC transporters. It has two apparent membrane
      spanning helices, one near the amino terminus and one near the carboxy terminus,
      and a large intervening loop that is predicted to reside in the periplasm. GldF
      and GldG are involved in membrane localization of GldA, suggesting that GldA,
      GldF, and GldG may interact to form a transporter. F. johnsoniae gldA is not
      closely linked to gldFG, but the gldA, gldF, and gldG homologs of the distantly
      related gliding bacterium Cytophaga hutchinsonii are arranged in what appears to
      be an operon. The exact roles of F. johnsoniae GldA, GldF, and GldG in gliding
      are not known. Sequence similarities of GldA to components of other ABC
      transporters suggest that the Gld transporter may be involved in export of some
      material to the periplasm, outer membrane, or beyond.

PMID- 11948150
TI  - Endotoxin of Neisseria meningitidis composed only of intact lipid A: inactivation
      of the meningococcal 3-deoxy-D-manno-octulosonic acid transferase.
AB  - Lipopolysaccharide, lipooligosaccharide (LOS), or endotoxin is important in
      bacterial survival and the pathogenesis of gram-negative bacteria. A necessary
      step in endotoxin biosynthesis is 3-deoxy-D-manno-octulosonic acid (Kdo)
      glycosylation of lipid A, catalyzed by the Kdo transferase KdtA (WaaA). In
      enteric gram-negative bacteria, this step is essential for survival. A nonpolar
      kdtA::aphA-3 mutation was created in Neisseria meningitidis via allelic exchange,
      and the mutant was viable. Detailed structural analysis demonstrated that the
      endotoxin of the kdtA::aphA-3 mutant was composed of fully acylated lipid A with
      variable phosphorylation but without Kdo glycosylation. In contrast to what
      happens in other gram-negative bacteria, tetra-acylated lipid IV(A) did not
      accumulate. The LOS structure of the kdtA::aphA-3 mutant was restored to the wild
      type structure by complementation with kdtA from N. meningitidis or Escherichia
      coli. The expression of a fully acylated, unglycosylated lipid A indicates that
      lipid A biosynthesis in N. meningitidis can proceed without the addition of Kdo
      and that KdtA is not essential for survival of the meningococcus.

PMID- 11948152
TI  - Novel carbohydrate-binding module of beta-1,3-xylanase from a marine bacterium,
      Alcaligenes sp. strain XY-234.
AB  - A beta-1,3-xylanase gene (txyA) from a marine bacterium, Alcaligenes sp. strain
      XY-234, has been cloned and sequenced. txyA consists of a 1,410-bp open reading
      frame that encodes 469 amino acid residues with a calculated molecular mass of
      52,256 Da. The domain structure of the beta-1,3-xylanase (TxyA) consists of a
      signal peptide of 22 amino acid residues, followed by a catalytic domain which
      belongs to family 26 of the glycosyl hydrolases, a linker region with one array
      of DGG and six repeats of DNGG, and a novel carbohydrate-binding module (CBM) at
      the C terminus. The recombinant TxyA hydrolyzed beta-1,3-xylan but not other
      polysaccharides such as beta-1,4-xylan, carboxymethylcellulose, curdlan,
      glucomannan, or beta-1,4-mannan. TxyA was capable of binding specifically to beta
      1,3-xylan. The analysis using truncated TxyA lacking either the N- or C-terminal
      region indicated that the region encoding the CBM was located between residues
      376 and 469. Binding studies on the CBM revealed that the K(d) and the maximum
      amount of protein bound to beta-1,3-xylan were 4.2 microM and 18.2 micromol/g of
      beta-1,3-xylan, respectively. Furthermore, comparison of the enzymatic properties
      between proteins with and without the CBM strongly indicated that the CBM of TxyA
      plays an important role in the hydrolysis of beta-1,3-xylan.

PMID- 11948151
TI  - Functional analysis of HrpF, a putative type III translocon protein from
      Xanthomonas campestris pv. vesicatoria.
AB  - Type III secretion systems (TTSSs) are specialized protein transport systems in
      gram-negative bacteria which target effector proteins into the host cell. The
      TTSS of the plant pathogen Xanthomonas campestris pv. vesicatoria, encoded by the
      hrp (hypersensitive reaction and pathogenicity) gene cluster, is essential for
      the interaction with the plant. One of the secreted proteins is HrpF, which is
      required for pathogenicity but dispensable for type III secretion of effector
      proteins in vitro, suggesting a role in translocation. In this study,
      complementation analyses of an hrpF null mutant strain using various deletion
      derivatives revealed the functional importance of the C-terminal hydrophobic
      protein region. Deletion of the N terminus abolished type III secretion of HrpF.
      Employing the type III effector AvrBs3 as a reporter, we show that the N terminus
      of HrpF contains a signal for secretion but not a functional translocation
      signal. Experiments with lipid bilayers revealed a lipid-binding activity of HrpF
      as well as HrpF-dependent pore formation. These data indicate that HrpF
      presumably plays a role at the bacterial-plant interface as part of a bacterial
      translocon which mediates effector protein delivery across the host cell
      membrane.

PMID- 11948153
TI  - Malonyl-coenzyme A reductase from Chloroflexus aurantiacus, a key enzyme of the 3
      hydroxypropionate cycle for autotrophic CO(2) fixation.
AB  - The 3-hydroxypropionate cycle is a new autotrophic CO(2) fixation pathway in
      Chloroflexus aurantiacus and some archaebacteria. The initial step is acetyl
      coenzyme A (CoA) carboxylation to malonyl-CoA by acetyl-CoA carboxylase, followed
      by NADPH-dependent reduction of malonyl-CoA to 3-hydroxypropionate. This
      reduction step was studied in Chloroflexus aurantiacus. A new enzyme was
      purified, malonyl-CoA reductase, which catalyzed the two-step reduction malonyl
      CoA + NADPH + H(+) --> malonate semialdehyde + NADP(+) + CoA and malonate
      semialdehyde + NADPH + H(+) --> 3-hydroxypropionate + NADP(+). The bifunctional
      enzyme (aldehyde dehydrogenase and alcohol dehydrogenase) had a native molecular
      mass of 300 kDa and consisted of a single large subunit of 145 kDa, suggesting an
      alpha(2) composition. The N-terminal amino acid sequence was determined, and the
      incomplete gene was identified in the genome database. Obviously, the enzyme
      consists of an N-terminal short-chain alcohol dehydrogenase domain and a C
      terminal aldehyde dehydrogenase domain. No indication of the presence of a
      prosthetic group was obtained; Mg(2+) and Fe(2+) stimulated and EDTA inhibited
      activity. The enzyme was highly specific for its substrates, with apparent K(m)
      values of 30 microM malonyl-CoA and 25 microM NADPH and a turnover number of 25
      s(-1) subunit(-1). The specific activity in autotrophically grown cells was 0.08
      micromol of malonyl-CoA reduced min(-1) (mg of protein)(-1), compared to 0.03
      micromol min(-1) (mg of protein)(-1) in heterotrophically grown cells, indicating
      downregulation under heterotrophic conditions. Malonyl-CoA reductase is not
      required in any other known pathway and therefore can be taken as a
      characteristic enzyme of the 3-hydroxypropionate cycle. Furthermore, the enzyme
      may be useful for production of 3-hydroxypropionate and for a coupled
      spectrophotometric assay for activity screening of acetyl-CoA carboxylase, a
      target enzyme of potent herbicides.

PMID- 11948154
TI  - Mobility of a restriction-modification system revealed by its genetic contexts in
      three hosts.
AB  - The flow of genes among prokaryotes plays a fundamental role in shaping bacterial
      evolution, and restriction-modification systems can modulate this flow. However,
      relatively little is known about the distribution and movement of restriction
      modification systems themselves. We have isolated and characterized the genes for
      restriction-modification systems from two species of Salmonella, S. enterica
      serovar Paratyphi A and S. enterica serovar Bareilly. Both systems are closely
      related to the PvuII restriction-modification system and share its target
      specificity. In the case of S. enterica serovar Paratyphi A, the restriction
      endonuclease is inactive, apparently due to a mutation in the subunit interface
      region. Unlike the chromosomally located Salmonella systems, the PvuII system is
      plasmid borne. We have completed the sequence characterization of the PvuII
      plasmid pPvu1, originally from Proteus vulgaris, making this the first completely
      sequenced plasmid from the genus Proteus. Despite the pronounced similarity of
      the three restriction-modification systems, the flanking sequences in Proteus and
      Salmonella are completely different. The SptAI and SbaI genes lie between an
      equivalent pair of bacteriophage P4-related open reading frames, one of which is
      a putative integrase gene, while the PvuII genes are adjacent to a mob operon and
      a XerCD recombination (cer) site.

PMID- 11948155
TI  - Demonstration that fbiC is required by Mycobacterium bovis BCG for coenzyme
      F(420) and FO biosynthesis.
AB  - Using the nitroimidazopyran-based antituberculosis drug PA-824 as a selective
      agent, transposon-generated Mycobacterium bovis strain BCG (M. bovis) mutants
      that could not make coenzyme F(420) were identified. Four independent mutants
      that could not make F(420) or the biosynthesis intermediate FO were examined more
      closely. These mutants contained transposons inserted in the M. bovis homologue
      of the Mycobacterium tuberculosis gene Rv1173, which we have named fbiC.
      Complementation of an M. bovis FbiC(-) mutant with fbiC restored the F(420)
      phenotype. These data demonstrate that fbiC is essential for F(420) production
      and that FbiC participates in a portion of the F(420) biosynthetic pathway
      between pyrimidinedione and FO. Homologues of fbiC were found in all 11
      microorganisms that have been fully sequenced and that are known to make F(420).
      Four of these homologues (all from members of the aerobic actinomycetes) coded
      for proteins homologous over the entire length of the M. bovis FbiC, but in seven
      microorganisms two separate genes were found to code for proteins homologous with
      either the N-terminal or C-terminal portions of the M. bovis FbiC. Histidine
      tagged FbiC overexpressed in Escherichia coli produced a fusion protein of the
      molecular mass predicted from the M. bovis BCG sequence (approximately 95,000
      Da), as well as three other histidine-tagged proteins of significantly smaller
      size, which are thought to be proteolysis products of the FbiC fusion protein.

PMID- 11948156
TI  - Rhodospirillum centenum utilizes separate motor and switch components to control
      lateral and polar flagellum rotation.
AB  - Rhodospirillum centenum is a purple photosynthetic bacterium that is capable of
      differentiating from vibrioid swimming cells that contain a single polar
      flagellum into rod-shaped swarming cells that have a polar flagellum plus
      numerous lateral flagella. Microscopic studies have demonstrated that the polar
      flagellum is constitutively present and that the lateral flagella are found only
      when the cells are grown on solidified or viscous medium. In this study, we
      demonstrated that R. centenum contains two sets of motor and switch genes, one
      set for the lateral flagella and the other for the polar flagellum. Electron
      microscopic analysis indicated that polar and lateral flagellum-specific FliG,
      FliM, and FliN switch proteins are necessary for assembly of the respective
      flagella. In contrast, separate polar and lateral MotA and MotB motor subunits
      are shown to be required for motility but are not needed for the synthesis of
      polar and lateral flagella. Phylogenetic analysis indicates that the polar and
      lateral FliG, FliM, and FliN switch proteins are closely related and most likely
      arose as a gene duplication event. However, phylogenetic analysis of the MotA and
      MotB motor subunits suggests that the polar flagellum may have obtained a set of
      motor genes through a lateral transfer event.

PMID- 11948158
TI  - Transcriptional interference by a complex formed at the centromere-like partition
      site of plasmid P1.
AB  - The partition site, parS, promotes accurate segregation of the replicated P1
      plasmid to daughter cells when the P1-encoded ParA and ParB proteins are
      supplied. The parS site was inserted into the Escherichia coli chromosome between
      the promoter and the structural gene for beta-galactosidase, lacZ. There was
      little interference with lacZ expression when ParA and ParB were supplied in
      trans. However, when a mutant ParA protein, ParAM314I, was supplied along with
      ParB, expression of lacZ was shut down. ParAM314I, ParB, and parS appear to form
      a nucleoprotein complex that blocks transcription. Mutations in parA and parB
      that relieved the parAM314I-dependent block were found. In addition, new
      mutations which impose the block were selected. Five of the latter mapped to parA
      and one to parB; all had a propagation-defective phenotype (Par(PD)) similar to
      that of parAM314I. Thus, whereas a null par mutant P1 plasmid segregates its DNA
      randomly, these mutants prevent even random distribution of the plasmid. We
      propose that ParA protein normally interacts transiently with the ParB-parS
      complex for partition to proceed but that the mutations block ParA dissociation.
      This "permanent" ParA-ParB-parS complex acts as a transcription block. Consistent
      with this hypothesis, we found that three of the seven blocking mutations lie
      within regions of ParA and ParB that are known to interact with each other. When
      the transcription block is imposed, regional silencing of nearby genes occurs.
      However, the requirement for ParA and a mutant parA or parB allele distinguishes
      the transcription block from the regional ParB-dependent gene silencing
      previously described.

PMID- 11948157
TI  - Identification of a gene cluster in Klebsiella pneumoniae which includes citX, a
      gene required for biosynthesis of the citrate lyase prosthetic group.
AB  - The biosynthesis of the 2'-(5"-phosphoribosyl)-3'-dephospho-coenzyme A (CoA)
      prosthetic group of citrate lyase (EC 4.1.3.6), a key enzyme of citrate
      fermentation, proceeds via the initial formation of the precursor 2'-(5"
      triphosphoribosyl)-3'-dephospho-CoA and subsequent transfer to apo-citrate lyase
      with removal of pyrophosphate. In Escherichia coli, the two steps are catalyzed
      by CitG and CitX, respectively, and the corresponding genes are part of the
      citrate lyase gene cluster, citCDEFXG. In the homologous citCDEFG operon of
      Klebsiella pneumoniae, citX is missing. A search for K. pneumoniae citX led to
      the identification of a second genome region involved in citrate fermentation
      which comprised the citWX genes and the divergent citYZ genes. The citX gene was
      confirmed to encode holo-citrate lyase synthase, whereas citW was shown to encode
      a citrate carrier, the third one identified in this species. The citYZ genes were
      found to encode a two-component system consisting of the sensor kinase CitY and
      the response regulator CitZ. Remarkably, both proteins showed >or=40% sequence
      identity to the citrate-sensing CitA-CitB two-component system, which is
      essential for the induction of the citrate fermentation genes in K. pneumoniae. A
      citZ insertion mutant was able to grow anaerobically with citrate, indicating
      that CitZ is not essential for expression of citrate fermentation genes. CitX
      synthesis was induced to a basal level under anaerobic conditions, independent of
      citrate, CitB, and CitZ, and to maximal levels during anaerobic growth with
      citrate as the sole carbon source. Similar to the other citrate fermentation
      enzymes, CitX synthesis was apparently subject to catabolite repression.

PMID- 11948160
TI  - Identification of [2Fe-2S] clusters in microbial ferrochelatases.
AB  - The terminal enzyme of heme biosynthesis, ferrochelatase (EC 4.99.1.1), catalyzes
      the insertion of ferrous iron into protoporphyrin IX to form protoheme. Prior to
      the present work, [2Fe-2S] clusters have been identified and characterized in
      animal ferrochelatases but not in plant or prokaryotic ferrochelatases. Herein we
      present evidence that ferrochelatases from the bacteria Caulobacter crescentus
      and Mycobacterium tuberculosis possess [2Fe-2S] clusters. The enzyme from C.
      crescentus is a homodimeric, membrane-associated protein while the enzyme from M.
      tuberculosis is monomeric and soluble. The clusters of the C. crescentus and M.
      tuberculosis ferrochelatases are ligated by four cysteines but possess ligand
      spacings that are unlike those of any previously characterized [2Fe-2S] cluster
      containing protein, including the ferrochelatase of the yeast Schizosaccharomyces
      pombe. Thus, the microbial ferrochelatases represent a new group of [2Fe-2S]
      cluster-containing proteins.

PMID- 11948159
TI  - A conserved C-terminal region in Gp71 of the small isometric-head phage LL-H and
      ORF474 of the prolate-head phage JCL1032 is implicated in specificity of
      adsorption of phage to its host, Lactobacillus delbrueckii.
AB  - Thirty-five phage-resistant mutants of Lactobacillus delbrueckii subsp. lactis
      ATCC 15808 were selected. Thirty-three of these mutants were assigned to the Bes
      group, while the remaining two were grouped under the Ads designation. Bes group
      mutants adsorbed phage LL-H but did not allow efficient phage development.
      Preliminary evidence suggests that these strains exhibit a mutation that changes
      the DNA specificity of a restriction-modification system. The Ads group mutants
      did not adsorb the small isometric-head phage LL-H. The results suggest that
      there are at least three different types of phage receptors in L. delbrueckii:
      two that are specific for small isometric-head phages and one that is specific
      for prolate-head phage JCL1032. Five LL-H host-range mutants which could overcome
      the adsorption block (a-type mutants) were selected and investigated by
      sequencing the genes g71 and g17, which encode minor and major tail proteins,
      respectively. Each of the a-type mutants carried a nucleotide change at the 3'
      end of gene g71. No mutations were observed in gene g17. Comparison of the gene
      product of g71 of phage LL-H with its homolog in JCL1032 (ORF474) showed that
      these proteins had very similar C-terminal regions. No similarities were found at
      the N-terminal part of the proteins. We conclude that the C-terminal portion of
      the protein encoded by g71 of phage LL-H and its homolog in phage JCL1032
      determines the adsorption specificities of these phages on L. delbrueckii.

PMID- 11948162
TI  - Firm but slippery attachment of Deinococcus geothermalis.
AB  - Bacterial biofilms impair the operation of many industrial processes. Deinococcus
      geothermalis is efficient primary biofilm former in paper machine water,
      functioning as an adhesion platform for secondary biofilm bacteria. It produces
      thick biofilms on various abiotic surfaces, but the mechanism of attachment is
      not known. High-resolution field-emission scanning electron microscopy and atomic
      force microscopy (AFM) showed peritrichous adhesion threads mediating the
      attachment of D. geothermalis E50051 to stainless steel and glass surfaces and
      cell-to-cell attachment, irrespective of the growth medium. Extensive slime
      matrix was absent from the D. geothermalis E50051 biofilms. AFM of the attached
      cells revealed regions on the cell surface with different topography,
      viscoelasticity, and adhesiveness, possibly representing different surface layers
      that were patchily exposed. We used oscillating probe techniques to keep the tip
      biofilm interactions as small as possible. In spite of this, AFM imaging of
      living D. geothermalis E50051 biofilms in water resulted in repositioning but not
      in detachment of the surface-attached cells. The irreversibly attached cells did
      not detach when pushed with a glass capillary but escaped the mechanical force by
      sliding along the surface. Air drying eliminated the flexibility of attachment,
      but it resumed after reimmersion in water. Biofilms were evaluated for their
      strength of attachment. D. geothermalis E50051 persisted 1 h of washing with 0.2%
      NaOH or 0.5% sodium dodecyl sulfate, in contrast to biofilms of Burkholderia
      cepacia F28L1 or the well-characterized biofilm former Staphylococcus epidermidis
      O-47. Deinococcus radiodurans strain DSM 20539(T) also formed tenacious biofilms.
      This paper shows that D. geothermalis has firm but laterally slippery attachment
      not reported before for a nonmotile species.

PMID- 11948161
TI  - The superoxide dismutase gene sodM is unique to Staphylococcus aureus: absence of
      sodM in coagulase-negative staphylococci.
AB  - Superoxide dismutase (SOD) profiles of clinical isolates of Staphylococcus aureus
      and coagulase-negative staphylococci (CoNS) were determined by using whole-cell
      lysates and activity gels. All S. aureus clinical isolates exhibited three
      closely migrating bands of activity as previously determined for laboratory
      strains of S. aureus: SodM, SodA, and a hybrid composed of SodM and SodA (M. W.
      Valderas and M. E. Hart, J. Bacteriol. 183:3399-3407, 2001). In contrast, the
      CoNS produced only one SOD activity, which migrated similarly to SodA of S.
      aureus. Southern analysis of eight CoNS species identified only a single sod gene
      in each case. A full-length sod gene was cloned from Staphylococcus epidermidis
      and determined to be more similar to sodA than to sodM of S. aureus. Therefore,
      this gene was designated sodA. The deduced amino acid sequence of the S.
      epidermidis sodA was 92 and 76% identical to that of the SodA and SodM proteins
      of S. aureus, respectively. The S. epidermidis sodA gene expressed from a plasmid
      complemented a sodA mutation in S. aureus, and the protein formed a hybrid with
      SodM of S. aureus. Both hybrid SOD forms as well as the SodM and SodA proteins of
      S. aureus and the S. epidermidis SodA protein exist as dimers. These data
      indicate that sodM is found only in S. aureus and not in the CoNS, suggesting an
      important divergence in the evolution of this genus and a unique role for SodM in
      S. aureus.

PMID- 11948163
TI  - nblS, a gene involved in controlling photosynthesis-related gene expression
      during high light and nutrient stress in Synechococcus elongatus PCC 7942.
AB  - The HliA protein of the cyanobacterium Synechococcus elongatus PCC 7942 is a
      small, thylakoid-associated protein that appears to play a role in
      photoprotection; its transcript rapidly accumulates in response to high-intensity
      light (HL) and the hli gene family is required for survival of cells in high
      light. In order to discover regulatory factors involved in HL acclimation in
      cyanobacteria, a screen was performed for chemically generated mutants unable to
      properly control expression of the hliA gene in response to HL. One such mutant
      was identified, and complementation analysis led to the identification of the
      affected gene, designated nblS. Based on its deduced protein sequence, NblS
      appears to be a membrane-bound, PAS-domain-bearing, sensor histidine kinase of
      two-component regulatory systems in bacteria. The nblS mutant was unable to
      properly control light intensity-mediated expression of several other
      photosynthesis-related genes, including all three psbA genes and the cpcBA genes.
      The mutant was also unable to control expression of the hliA and psbA genes in
      response to low-intensity blue/UV-A light, a response that may be related to the
      HL-mediated regulation of the genes. Additionally, in response to nutrient
      deprivation, the nblS mutant was unable to properly control accumulation of the
      nblA transcript and associated degradation of the light-harvesting
      phycobilisomes. The nblS mutant dies more rapidly than wild-type cells following
      exposure to HL or nutrient deprivation, likely due to its inability to properly
      acclimate to these stress conditions. Thus, the NblS protein is involved in the
      control of a number of processes critical for altering the photosynthetic
      apparatus in response to both HL and nutrient stress conditions.

PMID- 11948164
TI  - Newly identified cytochrome c oxidase operon in the nitrogen-fixing
      cyanobacterium Anabaena sp. strain PCC 7120 specifically induced in heterocysts.
AB  - Two operons have been cloned from Anabaena sp. strain PCC 7120 DNA, each of which
      encodes the three core subunits of distinct mitochondrial-type cytochrome c
      oxidases. The two operons are only 72 to 85% similar to one another at the
      nucleotide level in the most conserved subunit. One of these, coxBACII, is
      induced >20-fold in the middle to late stages of heterocyst differentiation.
      Analysis of green fluorescent protein reporters indicates that this operon is
      expressed specifically in proheterocysts and heterocysts. The other operon,
      coxBACI, is induced only 2.5-fold following nitrogen step-down and is expressed
      in all cells. Surprisingly, a disruption mutant of coxAII, the gene encoding
      subunit I of the heterocyst-specific oxidase, grows normally in the absence of
      combined nitrogen. It is likely that coxBACI and/or two other putative terminal
      oxidases present in the Anabaena sp. strain PCC 7120 genome are able to
      compensate for the loss of the heterocyst-specific oxidase in providing ATP for
      nitrogen fixation and maintaining a low oxygen level in heterocysts.

PMID- 11948166
TI  - Characterization of the interaction of Bacillus subtilis PyrR with pyr mRNA by
      site-directed mutagenesis of the protein.
AB  - The Bacillus subtilis PyrR protein regulates transcriptional attenuation of the
      pyrimidine nucleotide (pyr) operon by binding in a uridine nucleotide-dependent
      manner to specific sites on pyr mRNA and stabilizing a secondary structure of the
      downstream RNA that favors termination of transcription. The high-resolution
      structure of unliganded PyrR was used to guide site-directed mutagenesis of 12
      amino acid residues that were thought likely to be involved in the binding of
      RNA. Missense mutations were constructed and evaluated for their effects on
      regulation of pyr genes in vivo and their uracil phosphoribosyltransferase
      activity, which is catalyzed by wild-type PyrR. A substantial fraction of the
      mutant PyrR proteins did not have native structures, but eight PyrR mutants were
      purified and characterized physically, for their uracil phosphoribosyltransferase
      activity and for their ability to bind pyr RNA in vitro. On the basis of these
      studies Thr-18, His-22, Arg-141, and Arg-146 were implicated in RNA binding. Arg
      27 and Lys-152 were also likely to be involved in RNA binding, but Gln
      substitution mutations in these residues may have altered their subunit-subunit
      interactions slightly. Arg-19 was implicated in pyr regulation, but a specific
      role in RNA binding could not be demonstrated because the R19Q mutant protein
      could not be purified in native form. The results confirm a role in RNA binding
      of a positively charged face of PyrR previously identified from the
      crystallographic structure. The RNA binding residues lie in two sequence segments
      that are conserved in PyrR proteins from many species.

PMID- 11948167
TI  - Identification of an akinete marker gene in Anabaena variabilis.
AB  - Cyanobacteria that form akinetes as well as heterocysts present a rare
      opportunity to investigate the relationships between alternative differentiation
      processes and pattern formation processes in a single bacterium. Because no
      akinete marker gene has been identified, akinete formation has been little
      studied genetically. We report the first identification of an akinete marker
      gene.

PMID- 11948165
TI  - Bacillus subtilis functional genomics: global characterization of the stringent
      response by proteome and transcriptome analysis.
AB  - The stringent response in Bacillus subtilis was characterized by using proteome
      and transcriptome approaches. Comparison of protein synthesis patterns of wild
      type and relA mutant cells cultivated under conditions which provoke the
      stringent response revealed significant differences. According to their altered
      synthesis patterns in response to DL-norvaline, proteins were assigned to four
      distinct classes: (i) negative stringent control, i.e., strongly decreased
      protein synthesis in the wild type but not in the relA mutant (e.g., r-proteins);
      (ii) positive stringent control, i.e., induction of protein synthesis in the wild
      type only (e.g., YvyD and LeuD); (iii) proteins that were induced independently
      of RelA (e.g., YjcI); and (iv) proteins downregulated independently of RelA
      (e.g., glycolytic enzymes). Transcriptome studies based on DNA macroarray
      techniques were used to complement the proteome data, resulting in comparable
      induction and repression patterns of almost all corresponding genes. However, a
      comparison of both approaches revealed that only a subset of RelA-dependent genes
      or proteins was detectable by proteomics, demonstrating that the transcriptome
      approach allows a more comprehensive global gene expression profile analysis. The
      present study presents the first comprehensive description of the stringent
      response of a bacterial species and an almost complete map of protein-encoding
      genes affected by (p)ppGpp. The negative stringent control concerns reactions
      typical of growth and reproduction (ribosome synthesis, DNA synthesis, cell wall
      synthesis, etc.). Negatively controlled unknown y-genes may also code for
      proteins with a specific function during growth and reproduction (e.g., YlaG). On
      the other hand, many genes are induced in a RelA-dependent manner, including
      genes coding for already-known and as-yet-unknown proteins. A passive model is
      preferred to explain this positive control relying on the redistribution of the
      RNA polymerase under the influence of (p)ppGpp.

PMID- 11948169
TI  - Identification of fur and fldA homologs and a Pasteurella multocida tbpA homolog
      in Histophilus ovis and effects of iron availability on their transcription.
AB  - tbpA, fur, and fldA homologs from two strains (9L and 3384Y) of the sheep
      pathogen Histophilus ovis were sequenced. The predicted TbpA proteins of these
      strains are homologs of the Pasteurella multocida TbpA protein and collectively
      represent the second example of a new subfamily of TonB-dependent receptors. tbpA
      transcripts were readily detected by reverse transcription (RT)-PCR with RNA
      isolated from strain 9L grown under iron-restricted conditions in the presence or
      absence of bovine transferrin (Tf). However, with strain 3384Y and depending on
      the primer pair, tbpA transcripts were detected by RT-PCR predominantly when the
      RNA was from cells grown under iron-restricted conditions in the presence of
      bovine Tf. In both strains, the fldA homolog was found to be immediately upstream
      of fur and, based on RT-PCR, these genes are transcribed as a single unit; the
      availability of iron and the presence or absence of bovine Tf in the growth
      medium had no apparent effect on the relative amounts of the fldA-fur
      transcripts.

PMID- 11948168
TI  - Genetic organization of the Vibrio harveyi DnaA gene region and analysis of the
      function of the V. harveyi DnaA protein in Escherichia coli.
AB  - The Vibrionaceae family is distantly related to Enterobacteriaceae within the
      group of bacteria possessing the Dam methylase system. We have cloned, sequenced,
      and analyzed the dnaA gene region of Vibrio harveyi and found that although the
      organization of the V. harveyi dnaA region differs from that of Escherichia coli,
      the expression of both genes is autoregulated and ATP-DnaA binds cooperatively to
      ATP-DnaA boxes in the dnaA promoter region. The DnaA proteins of V. harveyi and
      E. coli are interchangeable and function nearly identically in controlling dnaA
      transcription and the initiation of chromosomal DNA replication despite the
      evolutionary distance between these bacteria.

PMID- 11948170
TI  - Overexpression of the Escherichia coli sugE gene confers resistance to a narrow
      range of quaternary ammonium compounds.
AB  - SugE of Escherichia coli, first identified as a suppressor of groEL mutations but
      a member of the small multidrug resistance family, has not previously been shown
      to confer a drug resistance phenotype. We show that high-level expression of sugE
      leads to resistance to a subset of toxic quaternary ammonium compounds.

PMID- 11948171
TI  - Analysis of the heat shock response of Neisseria meningitidis with cDNA- and
      oligonucleotide-based DNA microarrays.
AB  - Oligonucleotide- and cDNA-based microarrays comprising a subset of Neisseria
      meningitidis genes were assessed for study of the meningococcal heat shock
      response and found to be highly suitable for transcriptional profiling of N.
      meningitidis. Employing oligonucleotide arrays encompassing the entire genome of
      N. meningitidis, we analyzed the meningococcal heat shock response on a global
      scale and identified 55 heat shock-deregulated open reading frames (34 induced
      and 21 repressed).

PMID- 11948172
TI  - ZipA is required for recruitment of FtsK, FtsQ, FtsL, and FtsN to the septal ring
      in Escherichia coli.
AB  - The septal ring in Escherichia coli consists of at least nine essential gene
      products whose order of assembly resembles a mostly linear dependency pathway:
      FtsA and ZipA directly bind FtsZ polymers at the prospective division site,
      followed by the sequential addition of FtsK, FtsQ, FtsL, FtsW, FtsI, and FtsN.
      Recruitment of FtsK and all downstream components requires the prior localization
      of FtsA. Here we show that recruitment of FtsK, FtsQ, FtsL, and FtsN equally
      requires ZipA. The results imply that association of both FtsA and ZipA with FtsZ
      polymers is needed for further maturation of the nascent organelle.

PMID- 11948173
TI  - Nitrite reductase of Nitrosomonas europaea is not essential for production of
      gaseous nitrogen oxides and confers tolerance to nitrite.
AB  - A gene that encodes a periplasmic copper-type nitrite reductase (NirK) was
      identified in Nitrosomonas europaea. Disruption of this gene resulted in the
      disappearance of Nir activity in cell extracts. The nitrite tolerance of NirK
      deficient cells was lower than that of wild-type cells. Unexpectedly, NirK
      deficient cells still produced nitric oxide (NO) and nitrous oxide (N(2)O), the
      latter in greater amounts than that of wild-type cells. This demonstrates that
      NirK is not essential for the production of NO and N(2)O by N. europaea.
      Inactivation of the putative fnr gene showed that Fnr is not essential for the
      expression of nirK.

PMID- 11948174
TI  - Characterization of plasmid pRT1 from Pyrococcus sp. strain JT1.
AB  - We discovered a 3,373-bp plasmid (pRT1) in the hyperthermophilic archaeon
      Pyrococcus sp. strain JT1. Two major open reading frames were identified, and
      analysis of the sequence revealed some resemblance to motifs typically found in
      plasmids that replicate via a rolling-circle mechanism. The presence of single
      stranded DNA replication intermediates of pRT1 was detected, confirming this mode
      of replication.

PMID- 11948176
TI  - A new consensus sequence for phosphatidylserine recognition by annexins.
AB  - Annexins are abundant and ubiquitous proteins that bind, by their four
      structurally identical domain cores, to phosphatidylserine-containing membranes
      in the presence of Ca2+. Using molecular simulation and mutagenesis, we have
      identified a new phosphatidylserine-binding site in annexin V domain 1 and
      established its structure. The residues involved in this site constitute a
      consensus sequence highly conserved in all annexins. Remarkably, this consensus
      sequence is exclusively found in domains 1 or 2, sometimes in both, but never in
      domains 3 and 4. Such a pattern actually delineates three classes of annexins,
      shedding new light on the role played by the four-domain core of annexins that
      could encode specific information discriminating the different annexins that
      compete within a given cell for membrane binding. Our findings thus provide new
      strategies for understanding the regulation of the cellular functions of
      annexins.

PMID- 11948175
TI  - Mutations within the hMLH1 and hPMS2 subunits of the human MutLalpha mismatch
      repair factor affect its ATPase activity, but not its ability to interact with
      hMutSalpha.
AB  - The MutL family of mismatch repair proteins belongs to the GHKL class of ATPases,
      which contains also type II topoisomerases, HSP90, and histidine kinases. The
      nucleotide binding domains of these polypeptides are highly conserved, but this
      similarity has failed to help us understand the biological role of the ATPase
      activity of the MutL proteins in mismatch repair. hMutLalpha is a heterodimer of
      the human MutL homologues hMLH1 and hPMS2, and we decided to exploit its
      asymmetry to study this function. We now show that although the two subunits
      contribute differently to the ATPase activity of the heterodimer, hMutLalpha
      variants in which one subunit was able to bind but not hydrolyze ATP displayed
      similarly reduced mismatch repair activities in vitro. In contrast, variants in
      which either subunit was unable to bind the nucleotide were inactive. Mutation of
      the catalytic sites of both subunits abolished repair without altering the
      ability of these peptides to interact with one another. Since the binding of the
      nucleotide in hMutLalpha was not required for the formation of ternary complexes
      with the mismatch recognition factor hMutSalpha bound to a heteroduplex
      substrate, we propose that the ATPase activity of hMutLalpha is required
      downstream from this process.

PMID- 11948177
TI  - IQGAP1 is a component of Cdc42 signaling to the cytoskeleton.
AB  - The Ras-GAP related protein IQGAP1 binds several proteins, including actin,
      calmodulin, E-cadherin and the Rho family GTPase Cdc42. To gain insight into its
      in vivo function, IQGAP1 was overexpressed in mammalian cells. Transfection of
      IQGAP1 significantly increased the levels of active, GTP-bound Cdc42, resulting
      in the formation of peripheral actin microspikes. By contrast, transfection of an
      IQGAP1 mutant lacking part of the GAP-related domain (IQGAP1deltaGRD)
      substantially decreased the amount of GTP-bound Cdc42 in cell lysates. Consistent
      with these findings, IQGAP1DeltaGRD blocked Cdc42 function in cells that stably
      overexpress constitutively active Cdc42 and abrogated the effect of bradykinin on
      Cdc42. In cells transfected with IQGAP1deltaGRD, bradykinin was unable to
      activate Cdc42, translocate Cdc42 to the membrane fraction, or induce filopodia
      production. IQGAP1deltaGRD transfection altered cellular morphology, producing
      small, round cells that closely resemble Cdc42-/- cells. Some insight into the
      mechanism was provided by in vitro analysis, which revealed that IQGAP1deltaGRD
      increased the intrinsic GTPase activity of Cdc42, thereby increasing the amount
      of inactive, GDP-bound Cdc42. These data imply that IQGAP1 has a crucial role in
      transducing Cdc42 signaling to the cytoskeleton.

PMID- 11948178
TI  - Cloning and functional characterization of HDAC11, a novel member of the human
      histone deacetylase family.
AB  - We have cloned and characterized a human cDNA that belongs to the histone
      deacetylase family, which we designate as HDAC11. The predicted HDAC11 amino acid
      sequence reveals an open reading frame of 347 residues with a corresponding
      molecular mass of 39 kDa. Sequence analyses of the putative HDAC11 protein
      indicate that it contains conserved residues in the catalytic core regions shared
      by both class I and II mammalian HDAC enzymes. Putative orthologues of HDAC11
      exist in primate, mouse, Drosophila, and plant. Epitope-tagged HDAC11 protein
      expressed in mammalian cells displays histone deacetylase activity in vitro.
      Furthermore, HDAC11's enzymatic activity is inhibited by trapoxin, a known
      histone deacetylase inhibitor. Multiple tissue Northern blot and real-time PCR
      experiments show that the high expression level of HDAC11 transcripts is limited
      to kidney, heart, brain, skeletal muscle, and testis. Epitope-tagged HDAC11
      protein localizes predominantly to the cell nucleus. Co-immunoprecipitation
      experiments indicate that HDAC11 may be present in protein complexes that also
      contain HDAC6. These results indicate that HDAC11 is a novel and unique member of
      the histone deacetylase family and it may have distinct physiological roles from
      those of the known HDACs.

PMID- 11948179
TI  - The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4
      imidazolecarboxamide ribonucleotide transformylase/inosine 5'-monophosphate
      cyclohydrolase). A surprising lack of substrate channeling.
AB  - 5-Amino-4-imidazolecarboxamide ribonucleotide transformylase/IMP cyclohydrolase
      (ATIC) is a bifunctional protein possessing two enzymatic activities that
      sequentially catalyze the last two steps in the pathway for de novo synthesis of
      inosine 5'-monophosphate. This bifunctional enzyme is of particular interest
      because of its potential as a chemotherapeutic target. Furthermore, these two
      catalytic activities reside on the same protein throughout all of nature, raising
      the question of whether there is some kinetic advantage to the bifunctionality.
      Rapid chemical quench, stopped-flow absorbance, and steady-state kinetic
      techniques were used to elucidate the complete kinetic mechanism of human ATIC.
      The kinetic simulation program KINSIM was used to model the kinetic data obtained
      in this study. The detailed kinetic analysis, in combination with kinetic
      simulations, provided the following key features of the enzyme reaction pathway.
      1) The rate-limiting step in the overall reaction (2.9 +/- 0.4 s(-1)) is likely
      the release of tetrahydrofolate from the formyltransferase active site or a
      conformational change associated with tetrahydrofolate release. 2) The rate of
      the reverse transformylase reaction (6.7 s(-1)) is approximately 2-3-fold faster
      than the forward rate (2.9 s(-1)), whereas the cyclohydrolase reaction is
      essentially unidirectional in the forward sense. The cyclohydrolase reaction thus
      draws the overall bifunctional reaction toward the production of inosine
      monophosphate. 3) There was no kinetic evidence of substrate channeling of the
      intermediate, the formylaminoimidazole carboxamide ribonucleotide, between the
      formyltransferase and the cyclohydrolase active sites.

PMID- 11948180
TI  - p38 Mitogen-activated protein kinase mediates hypoxic regulation of Mdm2 and p53
      in neurons.
AB  - The multifunctional tumor suppressor protein, p53, inhibits cell growth and
      promotes differentiation and programmed cell death. p53 activity is controlled by
      transcriptional, translational, and post-translational regulation. A major
      pathway for post-translational regulation of p53 comprises its nucleocytoplasmic
      transport and subsequent proteasomal degradation, which involves binding to the
      oncoprotein, murine double minute-2 (Mdm2). Hypoxia and other stress signals
      cause cellular injury partly through the action of p53. In this study, we show
      that hypoxia induces down-regulation of Mdm2 as well as serine 15 phosphorylation
      and nuclear accumulation of p53 in cultured cortical neurons from E16 mice. These
      effects are diminished by the p38 mitogen-activated protein kinase inhibitors
      SB203580 and SB202190, but not by the inactive analog SB202474, and by a dominant
      interfering mutant of the p38-activating kinase mitogen-activated protein kinase
      kinase 3 (MKK3). Hypoxic neuronal death was also reduced by p38 inhibitors, by
      dominant-interfering MKK3, and by a p53-antisense oligodeoxynucleotide and was
      increased by a constitutively active form of p38 and by an Mdm2-antisense
      oligodeoxynucleotide. These results demonstrate that p38 and Mdm2 have roles in
      coupling hypoxic-ischemic neuronal insults to activation of p53 and hypoxic cell
      death.

PMID- 11948181
TI  - The p66Shc longevity gene is silenced through epigenetic modifications of an
      alternative promoter.
AB  - The mammal Shc locus encodes three overlapping isoforms (46, 52, and 66 kDa) that
      differ in the length of their N-terminal regions. p46/p52Shc and p66Shc have been
      implicated, respectively, in the cytoplasmic propagation of growth and
      apoptogenic signals. Levels of p66Shc expression correlate with life span
      duration in mice. p46Shc and p52Shc are ubiquitously expressed, whereas p66Shc is
      expressed in a cell lineage-specific fashion. However, the mechanisms underlying
      the regulation of Shc protein expression are unknown. Here we report the
      identification of two alternative promoters, driving the transcription of two
      mRNAs coding for p46/p52Shc and p66Shc. We show that treatment with an inhibitor
      of histone deacetylases or with a demethylating agent results in induction of
      p66Shc expression in cells that normally do not express this isoform but leaves
      the levels of the two other isoforms unchanged. Moreover, analysis of the
      methylation pattern of the p66Shc promoter in a panel of primary and immortalized
      human cells showed inverse correlation between p66Shc expression and methylation
      density of its promoter. These results identify histone deacetylation and
      cytosine methylation as the mechanisms underlying p66Shc silencing in
      nonexpressing cells.

PMID- 11948182
TI  - Substitutions of Phe61 located in the vicinity of template 5'-overhang influence
      polymerase fidelity and nucleoside analog sensitivity of HIV-1 reverse
      transcriptase.
AB  - Human immunodeficiency virus type 1 reverse transcriptase (RT) is an error-prone
      DNA polymerase. Structural determinants of its fidelity are incompletely
      understood. RT/template primer contacts have been shown to influence its fidelity
      and sensitivity to nucleoside analog inhibitors. The Phe(61) residue, located
      within the beta 3 sheet of the finger subdomain, is highly conserved among
      retroviral RTs. The crystal structure of a ternary complex revealed that Phe(61)
      contacts the first and second bases of the 5'-template overhang. To determine
      whether such contacts influence the dNTP-binding pocket, we performed a limited
      vertical scanning mutagenesis (Phe --> Ala, Leu, Trp, or Tyr) at Phe(61). The
      F61A mutant displayed the highest increase in fidelity, followed by the F61L and
      F61W variants, which had intermediate phenotypes. F61Y RT had a minimal effect.
      The increase in fidelity of the F61A mutant was corroborated by a 12-fold
      decrease in its forward mutation rate. The Phe(61) mutant RTs also displayed
      large reductions in sensitivity to 2',3'-dideoxythymidine triphosphate and 2',3'
      dideoxy,2'3'-didehydrothymidine triphosphate. Mutants displaying the largest
      increase in fidelity (F61A and F61L) were also the most resistant. These results
      suggest that contacts between the finger subdomain of human immunodeficiency
      virus type 1 RT and the template 5'-overhang are important determinants of the
      geometry of the dNTP-binding pocket.

PMID- 11948183
TI  - Essential role of the 58-kDa microspherule protein in the modulation of Daxx
      dependent transcriptional repression as revealed by nucleolar sequestration.
AB  - Daxx has been reported to mediate the Fas/JNK-dependent signals in the cytoplasm.
      However, several lines of evidence have suggested that Daxx is located mainly in
      the nucleus and functions as a transcriptional regulator. Recent studies have
      further indicated that Daxx-elicited transcriptional repression can be inhibited
      by the nuclear body-associated promyelocytic leukemia protein and apoptosis
      signal-regulating kinase 1 by sequestering Daxx to the nuclear bodies and the
      cytoplasm, respectively. Here, we further investigated the coordinated molecular
      mechanism by which Daxx function is regulated through protein-protein
      interaction. Using yeast two-hybrid screens to identify Daxx-interacting
      protein(s), three independent clones encoding the 58-kDa microspherule protein
      (MSP58) fragments were identified. Furthermore, we have demonstrated that Daxx
      interacts in vitro and in vivo with MSP58 via its NH(2)-terminal segment, which
      is distinct from the binding region of Fas, apoptosis signal-regulating kinase 1,
      and promyelocytic leukemia protein, suggesting a unique modulatory role of MSP58
      on Daxx function. Transient transfection experiments revealed that MSP58 relieves
      the repressor activity of Daxx in a dose-dependent manner in COS-1 and 293 cells
      but not in HeLa cells, implicating cell type-specific modulation of Daxx function
      by MSP58. Moreover, immunofluorescence analysis unequivocally demonstrated that
      MSP58 overexpression results in a translocation of Daxx to the enlarged nucleoli
      in COS-1 or 293 cells, whereas Daxx exhibited a diffuse nuclear pattern in HeLa
      cells. Taken together, these findings delineate a network of regulatory signaling
      pathways that converges on MSP58/Daxx interaction, causally associating Daxx
      nucleolus targeting with its transcriptional activation function.

PMID- 11948185
TI  - A nick-sensing DNA 3'-repair enzyme from Arabidopsis.
AB  - DNA single-strand breaks, a major cause of genome instability, often produce
      unconventional end groups that must be processed to restore terminal moieties
      suitable for reparative DNA gap filling or ligation. Here, we describe a
      bifunctional repair enzyme from Arabidopsis (named AtZDP) that recognizes DNA
      strand breaks and catalyzes the removal of 3'-end-blocking lesions. The isolated
      C-terminal domain of AtZDP is by itself competent for 3'-end processing, but not
      for strand break recognition. The N-terminal domain instead contains three Cys(3)
      His zinc fingers and recognizes various kinds of damaged double-stranded DNA.
      Gapped DNA molecules are preferential targets of AtZDP, which bends them by
      approximately 73 degrees upon binding, as measured by atomic force microscopy.
      Potential partners of AtZDP were identified in the Arabidopsis genome using the
      human single-strand break repairosome as a reference. These data identify a novel
      pathway for single-strand break repair in which a DNA-binding 3'-phosphoesterase
      acts as a "nick sensor" for damage recognition, as the catalyst of one repair
      step, and possibly as a nucleation center for the assembly of a fully competent
      repair complex.

PMID- 11948184
TI  - Ca(2+)-dependent inhibition of Na+/H+ exchanger 3 (NHE3) requires an NHE3-E3KARP
      alpha-actinin-4 complex for oligomerization and endocytosis.
AB  - Two PDZ domain-containing proteins, NHERF and E3KARP are necessary for cAMP
      dependent inhibition of Na(+)/H(+) exchanger 3 (NHE3). In this study, we
      demonstrate a specific role of E3KARP, which is not duplicated by NHERF, in
      Ca(2+)-dependent inhibition of NHE3 activity. NHE3 activity is inhibited by
      elevation of intracellular Ca(2+) ([Ca(2+)](i)) in PS120 fibroblasts stably
      expressing E3KARP but not those expressing NHERF. In addition, this Ca(2+)
      dependent inhibition requires Ca(2+)-dependent association between alpha-actinin
      4 and E3KARP. NHE3 is indirectly connected to alpha-actinin-4 in a protein
      complex through Ca(2+)-dependent interaction between alpha-actinin-4 and E3KARP,
      which occurs through the actin-binding domain plus spectrin repeat domain of
      alpha-actinin-4. Elevation of [Ca(2+)](i) results in oligomerization and
      endocytosis of NHE3 as well as in inhibition of NHE3 activity. Overexpression of
      alpha-actinin-4 potentiates the inhibitory effect of ionomycin on NHE3 activity
      by accelerating the oligomerization and endocytosis of NHE3. In contrast,
      overexpression of the actin-binding domain plus spectrin repeat domain acts as a
      dominant-negative mutant and prevents the inhibitory effect of ionomycin on NHE3
      activity as well as the oligomerization and internalization of NHE3. From these
      results, we propose that elevated Ca(2+) inhibits NHE3 activity through
      oligomerization and endocytosis of NHE3, which occurs via formation of an NHE3
      E3KARP-alpha-actinin-4 complex.

PMID- 11948186
TI  - Pore-forming polypeptides of the pathogenic protozoon Naegleria fowleri.
AB  - The free-living amoeboflagellate and potential human pathogen Naegleria fowleri
      causes the often fatal disease primary amoebic meningoencephalitis. The molecular
      repertoire responsible for the cytolytic and tissue-destructive activity of this
      amoeboid protozoon is largely unknown. We isolated two pore-forming polypeptides
      from extracts of highly virulent trophozoites of N. fowleri by measuring their
      membrane-permeabilizing activity. N-terminal sequencing and subsequent molecular
      cloning yielded the complete primary structures and revealed that the two
      polypeptides are isoforms. Both polypeptides share similar structural properties
      with antimicrobial and cytolytic polypeptides of the protozoon Entamoeba
      histolytica (amoebapores) and of cytotoxic natural killer (NK) and T cells of
      human (granulysin) and pig (NK-lysin), all characterized by a structure of
      amphipathic alpha-helices and an invariant framework of cysteine residues
      involved in disulfide bonds. In contrast to the aforementioned proteins, the
      Naegleria polypeptides both are processed from large precursor molecules
      containing additional isoforms of substantial sequence divergence. Moreover,
      biochemical characterization of the isolated polypeptides in combination with
      mass determination showed that they are N-glycosylated and variably processed at
      the C terminus. The biological activity of the purified polypeptides of Naegleria
      was examined toward human cells and bacteria, and it was found that these
      factors, named naegleriapores, are active against both types of target cells,
      which is in good agreement with their proposed biological role as a broad
      spectrum effector molecule.

PMID- 11948187
TI  - Positive feedback regulation between Akt2 and MyoD during muscle differentiation.
      Cloning of Akt2 promoter.
AB  - Akt2 is a member of the Akt/PKB family, which is involved in a variety of
      cellular events including cell survival, proliferation, and differentiation.
      During skeletal muscle differentiation, the Akt2 but not Akt1 expression was
      significantly increased. Microinjection of anti-Akt2 but not anti-Akt1 antibody
      efficiently abrogated myogenesis, indicating that Akt2 plays a specific role in
      muscle differentiation. It has been well documented that ectopic expression of
      MyoD is sufficient to induce muscle differentiation in myoblasts. However, the
      mechanism of induction of Akt2 during muscle differentiation and the significance
      of Akt2 protein in MyoD-induced myogenesis are largely unknown. In this study, we
      provide direct evidence that Akt2 is transcriptionally regulated by MyoD and
      activates MyoD-myocyte enhancer binding factor-2 (MEF2) transactivation activity.
      The Akt2 promoter was isolated and found to contain nine putative E-boxes
      (CANNTG), which are putative MyoD binding sites. Electrophoretic mobility shift
      analyses revealed that MyoD bound to eight of the sites. The expression of MyoD
      significantly enhanced Akt2 promoter activity and up-regulated Akt2 mRNA and
      protein levels. Moreover, Akt2 but not Akt1 was activated during differentiation.
      The expression of Akt2 activated MyoD-MEF2 transcriptional activity and induced
      myogenin expression. These data indicate that there is a positive feedback
      regulation loop between Akt2 and MyoD-MEF2 during muscle differentiation, which
      is essential for MyoD-induced myogenesis.

PMID- 11948188
TI  - Differential regulation of gene expression by PITX2 isoforms.
AB  - Three major PITX2 isoforms are differentially expressed in human, mice,
      zebrafish, chick, and frog tissues. To demonstrate differential regulation of
      gene expression by these isoforms we used three different promoters and three
      cell lines. Transient transfection of Chinese hamster ovary, HeLa, and LS-8 cell
      lines revealed differences in PITX2A and PITX2C activation of the PLOD1 and Dlx2
      promoters, however, PITX2B is inactive. In contrast, PITX2B actives the pituitary
      specific Prolactin promoter at higher levels than either PITX2A or PITX2C.
      Interestingly, co-transfection of either PITX2A or PITX2C with PITX2B results in
      a synergistic activation of the PLOD1 and Dlx2 promoters. Furthermore, PITX2
      isoforms have different transcriptional activity dependent upon the cells used
      for transfection analysis. We have isolated a fourth PITX2 isoform (PITX2D)
      expressed only in humans, which acts to suppress the transcriptional activity of
      the other PITX2 isoforms. Electrophoretic mobility shift assays and glutathione S
      transferase pull-down experiments demonstrated that all isoforms interact with
      PITX2D and that PITX2B forms heterodimeric complexes with PITX2A and PITX2C. Our
      research provides a molecular basis for differential gene regulation through the
      expression of PITX2 isoforms. PITX2 isoform activities are both promoter- and
      cell-specific, and our data reveal new mechanisms for PITX2-regulated gene
      expression.

PMID- 11948189
TI  - DNA ligase I competes with FEN1 to expand repetitive DNA sequences in vitro.
AB  - Repeat sequences in various genomes undergo expansion by poorly understood
      mechanisms. By using an oligonucleotide system containing such repeats, we
      recapitulated the last steps in Okazaki fragment processing, which have been
      implicated in sequence expansion. A template containing either triplet or tandem
      repeats was annealed to a downstream primer containing complementary repeats at
      its 5'-end. Overlapping upstream primers, designed to strand-displace varying
      numbers of repeats in the downstream primer, were annealed. Human DNA ligase I
      joined overlapping segments of repeats generating an expansion product from the
      primer strands. Joining efficiency decreased with repeat length. Flap
      endonuclease 1 (FEN1) cleaved the displaced downstream strand and together with
      DNA ligase I produced non-expanded products. However, both expanded and non
      expanded products formed irrespective of relative nuclease and ligase
      concentrations tested or enzyme addition order, suggesting the pre-existence and
      persistence of intermediates leading to both outcomes. FEN1 activity decreased
      with the length of repeat segment displaced presumably because the flap forms
      structures that inhibit cleavage. Increased MgCl(2) disfavored ligation of
      substrate intermediates that result in expansion products. Examination of
      expansion in vitro enables dissection of substrate and replication enzyme
      dynamics on repeat sequences.

PMID- 11948191
TI  - Stopped-flow kinetic analysis of the reaction catalyzed by the full-length yeast
      cystathionine beta-synthase.
AB  - Cystathionine beta-synthase found in yeast catalyzes a pyridoxal phosphate
      dependent condensation of homocysteine and serine to form cystathionine. Unlike
      the homologous mammalian enzymes, yeast cystathionine beta-synthase lacks a
      second cofactor, heme, which facilitates detailed kinetic studies of the enzyme
      because the different pyridoxal phosphate-bound intermediates can be followed by
      their characteristic absorption spectra. We conducted a rapid reaction kinetic
      analysis of the full-length yeast enzyme in the forward and reverse directions.
      In the forward direction, we observed formation of the external aldimine of
      serine (14 mm(-1) s(-1)) and the aminoacrylate intermediate (15 s(-1)).
      Homocysteine binds to the aminoacrylate with a bimolecular rate constant of 35
      mm(-1) s(-1) and rapidly converts to cystathionine (180 s(-1)), leading to the
      accumulation of a 420 nm absorbing species, which has been assigned as the
      external aldimine of cystathionine. Release of cystathionine is slow (k = 2.3 s(
      1)), which is similar to k(cat) (1.7 s(-1)) at 15 degrees C, consistent with this
      being a rate-determining step. In the reverse direction, cystathionine binds to
      the enzyme with a bimolecular rate constant of 1.5 mm(-1) s(-1) and is rapidly
      converted to the aminoacrylate without accumulation of the external aldimine. The
      kinetic behavior of the full-length enzyme shows notable differences from that
      reported for a truncated form of the enzyme lacking the C-terminal third of the
      protein (Jhee, K. H., Niks, D., McPhie, P., Dunn, M. F., and Miles, E. W. (2001)
      Biochemistry 40, 10873-10880).

PMID- 11948190
TI  - Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision
      DNA repair in association with PARP-1 and XRCC1.
AB  - The DNA damage dependence of poly(ADP-ribose) polymerase-2 (PARP-2) activity is
      suggestive of its implication in genome surveillance and protection. Here we show
      that the PARP-2 gene, mainly expressed in actively dividing tissues follows, but
      to a smaller extent, that of PARP-1 during mouse development. We found that PARP
      2 and PARP-1 homo- and heterodimerize; the interacting interfaces, sites of
      reciprocal modification, have been mapped. PARP-2 was also found to interact with
      three other proteins involved in the base excision repair pathway: x-ray cross
      complementing factor 1 (XRCC1), DNA polymerase beta, and DNA ligase III, already
      known as partners of PARP-1. XRCC1 negatively regulates PARP-2 activity, as it
      does for PARP-1, while being a polymer acceptor for both PARP-1 and PARP-2. To
      gain insight into the physiological role of PARP-2 in response to genotoxic
      stress, we developed by gene disruption mice deficient in PARP-2. Following
      treatment by the alkylating agent N-nitroso-N-methylurea (MNU), PARP-2-deficient
      cells displayed an important delay in DNA strand breaks resealing, similar to
      that observed in PARP-1 deficient cells, thus confirming that PARP-2 is also an
      active player in base excision repair despite its low capacity to synthesize ADP
      ribose polymers.

PMID- 11948192
TI  - Purification and characterization of yeast Sco1p, a mitochondrial copper protein.
AB  - The present studies were undertaken to further characterize the properties of
      Sco1p, a constituent of the mitochondrial inner membrane implicated in copper
      transfer to cytochrome oxidase. We report a procedure capable of yielding Sco1p
      of >95% purity. Sco1p has been purified from strains of Saccharomyces cerevisiae
      that overexpress the protein. The amino-terminal sequence of purified Sco1p
      indicates that the first 40 amino acids of the primary translation product
      constitute a mitochondrial targeting sequence that is proteolytically cleaved
      during import. We estimate that Sco1p constitutes 0.08% total mitochondrial
      proteins in wild type yeast and 5% in the transformant used for the purification.
      Sco1p contains approximately 1 mol of copper/mol protein. The copper is not
      removed by the treatment of Sco1p with EDTA, indicating that it is bound with
      high affinity. Purified Sco1p sediments identical to Sco1p in crude extracts of
      mitochondria from wild type yeast or from a strain transformed with SCO1 on a
      high copy plasmid. Native Sco1p has an estimated mass of 88 kDa, suggesting that
      it is a homotrimer. Sco1p expressed as a soluble protein lacking the internal 17
      amino acids of the membrane-anchoring domain has been localized in the matrix.
      The protein has also been targeted to the intermembrane space. Neither soluble
      matrix nor intermembrane-localized Sco1p is able to complement a sco1 mutant,
      suggesting that only the membrane form with the carboxyl-terminal domain facing
      the intermembrane space is able to exert its normal function.

PMID- 11948193
TI  - Purification and characterization of the Escherichia coli exoribonuclease RNase
      R. Comparison with RNase II.
AB  - Escherichia coli RNase R, a 3' --> 5' exoribonuclease homologous to RNase II, was
      overexpressed and purified to near homogeneity in its native untagged form by a
      rapid procedure. The purified enzyme was free of nucleic acid. It migrated upon
      gel filtration chromatography as a monomer with an apparent molecular mass of
      approximately 95 kDa, in close agreement with its expected size based on the
      sequence of the rnr gene. RNase R was most active at pH 7.5-9.5 in the presence
      of 0.1-0.5 mm Mg(2+) and 50-500 mm KCl. The enzyme shares many catalytic
      properties with RNase II. Both enzymes are nonspecific processive ribonucleases
      that release 5'-nucleotide monophosphates and leave a short undigested
      oligonucleotide core. However, whereas RNase R shortens RNA processively to di-
      and trinucleotides, RNase II becomes more distributive when the length of the
      substrate reaches approximately 10 nucleotides, and it leaves an undigested core
      of 3-5 nucleotides. Both enzymes work on substrates with a 3'-phosphate group.
      RNase R and RNase II are most active on synthetic homopolymers such as poly(A),
      but their substrate specificities differ. RNase II is more active on poly(A),
      whereas RNase R is much more active on rRNAs. Neither RNase R nor RNase II can
      degrade a complete RNA-RNA or DNA-RNA hybrid or one with a 4-nucleotide 3'-RNA
      overhang. RNase R differs from RNase II in that it cannot digest DNA oligomers
      and is not inhibited by such molecules, suggesting that it does not bind DNA.
      Although the in vivo function of RNase R is not known, its ability to digest
      certain natural RNAs may explain why it is maintained in E. coli together with
      RNase II.

PMID- 11948194
TI  - Host defense responses to infection by Mycobacterium tuberculosis. Induction of
      IRF-1 and a serine protease inhibitor.
AB  - Alveolar macrophages and newly recruited monocytes are targets of infection by
      Mycobacterium tuberculosis. Therefore, we examined the expression of interferon
      regulatory factor 1 (IRF-1), which plays an important role in host defense
      against M. tuberculosis, in undifferentiated and differentiated cells. Infection
      induced IRF-1 in both. IRF-1 from undifferentiated, uninfected monocytic cell
      lines was modified during extraction to produce specific species that were
      apparently smaller than intact IRF-1. After infection by M. tuberculosis or
      differentiation, intact IRF-1 was recovered. Subcellular fractions were assayed
      for the ability to modify IRF-1 or inhibit its modification. A serine protease on
      the cytoplasmic surface of an organelle or vesicle in the
      "lysosomal/mitochondrial" fraction from undifferentiated cells was responsible
      for the modification of IRF-1. Thus, the simplest explanation of the modification
      is cleavage of IRF-1 by the serine protease. Recovery of intact IRF-1 correlated
      with induction of a serine protease inhibitor that was able to significantly
      reduce the modification of IRF-1. The inhibitor was present in the cytoplasm of
      M. tuberculosis-infected or -differentiated cells. It is likely that induction of
      both IRF-1 and the serine protease inhibitor in response to infection by M.
      tuberculosis represent host defense mechanisms.

PMID- 11948196
TI  - Buoyancy and maximal diving depth in penguins: do they control inhaling air
      volume?
AB  - Using a newly developed data logger to measure acceleration, we demonstrate that
      free-ranging king and Adelie penguins only beat their flippers substantially
      during the first part of descent or when they were presumed to be chasing prey at
      the bottom of dives. Flipper beating stopped during the latter part of ascent: at
      29+/-9 % (mean +/- S.D.) of dive depth (mean dive depth=136.8+/-145.1 m, N=425
      dives) in king penguins, and at 52+/-20 % of dive depth (mean dive depth=72.9+/
      70.5 m, N=664 dives) in Adelie penguins. Propulsive swim speeds of both species
      were approximately 2 m s(-1) during dives; however, a marked increase in speed,
      up to approximately 2.9 m s(-1), sometimes occurred in king penguins during the
      passive ascending periods. During the prolonged ascending, oblique ascent angle
      and slowdown near the surface may represent one way to avoid the potential risk
      of decompression sickness. Biomechanical calculations for data from free-ranging
      king and Adelie penguins indicate that the air volume of the birds (respiratory
      system and plumage) can provide enough buoyancy for the passive ascent. When
      comparing the passive ascents for shallow and deep dives, there is a positive
      correlation between air volume and the depth of the dive. This suggests that
      penguins regulate their air volume to optimize the costs and benefits of
      buoyancy.

PMID- 11948195
TI  - Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array
      analysis.
AB  - Antisense oligonucleotides are potentially powerful tools for selective control
      of cellular and viral gene expression. Crucial to successful application of this
      approach is the specificity of the oligonucleotide for the chosen RNA target.
      Here we apply DNA array technology to examine the specificity of antisense
      oligonucleotide treatments. The molecules used in these studies consisted of
      phosphorothioate oligomers linked to the Antennapedia (Ant) delivery peptide. The
      antisense oligonucleotide component was complementary to a site flanking the AUG
      of the MDR1 message, which codes for P-glycoprotein, a membrane ATPase associated
      with multidrug resistance in tumor cells. Using a DNA array of 2059 genes, we
      analyzed cellular responses to molecules comprised of Ant peptide-oligonucleotide
      conjugates, as well as to the Ant peptide alone. Besides the expected reduction
      in MDR1 message level, 37 other genes (approximately 2% of those tested) showed
      changes of comparable magnitude. The validity of the array results was confirmed
      for selected genes using Northern blots to assess messenger RNA levels. These
      results suggest that studies using antisense oligonucleotide technology to
      modulate gene expression need to be interpreted with caution.

PMID- 11948197
TI  - The mechanical basis of Drosophila audition.
AB  - In Drosophila melanogaster, antennal hearing organs mediate the detection of
      conspecific songs. Combining laser Doppler vibrometry, acoustic near-field
      measurements and anatomical analysis, we have investigated the first steps in
      Drosophila audition, i.e. the conversion of acoustic energy into mechanical
      vibrations and the subsequent transmission of vibrations to the auditory
      receptors in the base of the antenna. Examination of the mechanical responses of
      the antennal structures established that the distal antennal parts (the funiculus
      and the arista) together constitute a mechanical entity, the sound receiver.
      Unconventionally, this receiver is asymmetric, resulting in an unusual, rotatory
      pattern of vibration; in the presence of sound, the arista and the funiculus
      together rotate about the longitudinal axis of the latter. According to the
      mechanical response characteristics, the antennal receiver represents a
      moderately damped simple harmonic oscillator. The receiver's resonance frequency
      increases continuously with the stimulus intensity, demonstrating the presence of
      a non-linear stiffness that may be introduced by the auditory sense organ. This
      surprising, non-linear effect is relevant for close-range acoustic communication
      in Drosophila; by improving antennal sensitivity at low song intensities and
      reducing sensitivity when intensity is high, it brings about dynamic range
      compression in the fly's auditory system.

PMID- 11948199
TI  - Urine makes the difference: chemical communication in fighting crayfish made
      visible.
AB  - Chemical communication is a widespread phenomenon in aquatic animals but is
      difficult to investigate because the signals are not visible. Here, we present
      the results of a study into chemical communication in blindfolded fighting
      crayfish (Astacus leptodactylus) in which we employed a new method: visualisation
      of urine using the dye Fluorescein. The probability of urine release is greater
      during fights than during non-social activities or inactivity. The eventual
      winners are more likely to release urine during fights than the eventual losers.
      In both winners and losers, urine release is coupled to offensive behaviours, and
      the probability of urine release increases with increasing levels of aggression.
      In A. leptodactylus, urine is carried to the opponent by the forward-projecting
      gill currents. During spontaneous release, urine is fanned laterally with the aid
      of the exopodites of the maxillipeds. Aggressive behaviour is effective in
      intimidating blindfolded opponents only in conjunction with urine release:
      receivers decrease offensive behaviour and increase defensive behaviour.
      Aggressive behaviour alone does not intimidate opponents. The loser of a recent
      fight is deterred equally well by a familiar and an unfamiliar opponent. Hence,
      in crayfish, individual recognition of the urine scent of a dominant individual
      does not appear to be significant for the maintenance of dominance hierarchies.
      Our results suggest that urine contains information about the fighting ability
      and/or aggressiveness of the signaller. The chemical signals thus far
      unidentified appear to be important in determining the outcome of a fight.

PMID- 11948198
TI  - Characterization of yeast V-ATPase mutants lacking Vph1p or Stv1p and the effect
      on endocytosis.
AB  - Subunit a of V-ATPase in the yeast Saccharomyces cerevisiae, in contrast to its
      other subunits, is encoded by two genes VPH1 and STV1. While disruption of any
      other gene encoding the V-ATPase subunits results in growth arrest at pH 7.5,
      null mutants of Vph1p or Stv1p can grow at this pH. We used a polyclonal antibody
      to yeast Stv1p and a commercially available monoclonal antibody to Vph1p for
      analysis of yeast membranes by sucrose gradient fractionation, and two different
      vital dyes to characterize the phenotype of vph1 triangle up and stv1 triangle up
      mutants as compared to the double mutant and the wild-type cells. Immunological
      assays of sucrose gradient fractions revealed that the amount of Stv1p was
      elevated in the vph1 triangle up strain, and that vacuoles purified by this
      method with no detectable endosomal contamination contain an assembled V-ATPase
      complex, but with much lower activity than the wild type. These results suggest
      that Stv1p compensates for the loss of Vph1p in the vph1 triangle up strain.
      LysoSensor Green DND-189 was used as a pH sensor to demonstrate unexpected
      changes in vacuolar acidification in stv1 triangle up as the Vph1p-containing V
      ATPase complex is commonly considered to acidify the vacuoles. In the vph1
      triangle up strain, the dye revealed slight but definite acidification of the
      vacuole as well. The lipophilic dye FM4-64 was used as an endocytic marker. We
      show that the null V-ATPase mutants, as well as the vph1 triangle up one,
      markedly slow down endocytosis of the dye.

PMID- 11948200
TI  - Drosophila as a new model organism for the neurobiology of aggression?
AB  - We report here the effects of several neurobiological determinants on aggressive
      behaviour in the fruitfly Drosophila melanogaster. This study combines
      behavioural, transgenic, genetic and pharmacological techniques that are well
      established in the fruitfly, in the novel context of the neurobiology of
      aggression. We find that octopamine, dopamine and a region in the Drosophila
      brain called the mushroom bodies, all profoundly influence the expression of
      aggressive behaviour. Serotonin had no effect. We conclude that Drosophila, with
      its advanced set of molecular tools and its behavioural richness, has the
      potential to develop into a new model organism for the study of the neurobiology
      of aggression.

PMID- 11948201
TI  - Independent and conjugate eye movements during optokinesis in teleost fish.
AB  - In response to movements involving a large part of the visual field, the eyes of
      vertebrates typically show an optokinetic nystagmus, a response in which both
      eyes are tightly yoked. Using a comparative approach, this study sets out to
      establish whether fish with independent spontaneous eye movements show
      independent optokinetic nystagmus in each eye. Two fish with independent
      spontaneous eye movements, the pipefish Corythoichthyes intestinalis and the
      sandlance Limnichthyes fasciatus were compared with the butterflyfish Chaetodon
      rainfordi, which exhibits tightly yoked eye movements. In the butterflyfish a
      single whole-field stimulus elicits conjugate optokinesis, whereas the sandlance
      and pipefish show asynchronous optokinetic movements. In a split drum experiment,
      when both eyes were stimulated in opposite directions with different speeds, both
      the sandlance and the pipefish compensated independently with each eye. The
      optokinetic response in the butterflyfish showed some disconjugacy but was
      generally confused. When one eye was occluded, the seeing eye was capable of
      driving the occluded eye in both the butterflyfish and the pipefish but not in
      the sandlance. Monocular occlusion therefore unmasks a link between the two eyes
      in the pipefish, which is overridden when both eyes receive visual input. The
      sandlance never showed any correlation between the eyes during optokinesis in all
      stimulus conditions. This suggests that there are different levels of linkage
      between the two eyes in the oculomotor system of teleosts, depending on the
      visual input.

PMID- 11948202
TI  - Energetics of median and paired fin swimming, body and caudal fin swimming, and
      gait transition in parrotfish (Scarus schlegeli) and triggerfish (Rhinecanthus
      aculeatus).
AB  - To determine the energetic costs of rigid-body, median or paired-fin (MPF)
      swimming versus undulatory, body-caudal fin (BCF) swimming, we measured oxygen
      consumption as a function of swimming speed in two MPF swimming specialists,
      Schlegel's parrotfish and Picasso triggerfish. The parrotfish swam exclusively
      with the pectoral fins at prolonged swimming speeds up to 3.2 total lengths per
      second (L s(-1); 30 min critical swimming speed, U(crit)). At higher speeds, gait
      transferred to a burst-and-coast BCF swimming mode that resulted in rapid
      fatigue. The triggerfish swam using undulations of the soft dorsal and anal fins
      up to 1.5 L s(-1), beyond which BCF undulations were recruited intermittently.
      BCF swimming was used continuously above 3.5 L s(-1), and was accompanied by
      synchronous undulations of the dorsal and anal fins. The triggerfish were capable
      of high, prolonged swimming speeds of up to 4.1 L s(-1) (30 min U(crit)). In both
      species, the rates of increase in oxygen consumption with swimming speed were
      higher during BCF swimming than during rigid-body MPF swimming. Our results
      indicate that, for these species, undulatory swimming is energetically more
      costly than rigid-body swimming, and therefore support the hypothesis that MPF
      swimming is more efficient. In addition, use of the BCF gait at higher swimming
      speed increased the cost of transport in both species beyond that predicted for
      MPF swimming at the same speeds. This suggests that, unlike for terrestrial
      locomotion, gait transition in fishes does not occur to reduce energetic costs,
      but to increase recruitable muscle mass and propulsive surfaces. The appropriate
      use of the power and exponential functions to model swimming energetics is also
      discussed.

PMID- 11948204
TI  - Force enhancement following stretching of skeletal muscle: a new mechanism.
AB  - We investigated force enhancement following stretching in the in situ cat soleus
      muscle on the ascending and descending limb of the force-length relationship by
      varying the amount and speed of stretching and the frequency of activation (5 Hz,
      30 Hz). There was a small but consistent (P<0.05) amount of force enhancement
      following muscle stretching on the ascending limb of the force-length
      relationship for both stimulation frequencies. The steady-state active isometric
      forces following stretches of 9 mm on the descending limb of the force-length
      relationship were always equal to or greater than the corresponding forces from
      the purely isometric contractions at the length at which the stretch was started.
      Therefore, force production for these trials showed positive stiffness and was
      associated with stable behavior. Following active stretching of cat soleus on the
      descending limb of the force-length relationship, the passive forces at the end
      of the test were significantly greater than the corresponding passive forces for
      purely isometric contractions, or the passive forces following stretching of the
      passive muscle. This passive force enhancement following active stretching
      increased with increasing magnitude of stretch, was not associated with
      structural damage, and only disappeared once the muscle was shortened. For
      stretches of 6 mm and 9 mm, the passive force enhancement accounted for more than
      50 % of the total force enhancement, reaching a peak contribution of 83.7 % for
      the stretches of 9 mm at a speed of 3 mm s(-1). The results of this study suggest
      that a passive structural element provides a great part of the force enhancement
      on the descending limb of the force-length relationship of the cat soleus.
      Furthermore, the results indicate that mechanisms other than sarcomere length non
      uniformity alone are operative.

PMID- 11948203
TI  - Redistribution of immunofluorescence of CFTR anion channel and NKCC cotransporter
      in chloride cells during adaptation of the killifish Fundulus heteroclitus to sea
      water.
AB  - Cellular distribution of cystic fibrosis transmembrane conductance regulator
      (CFTR) immunofluorescence was detected by monoclonal antibody directed to the C
      terminus of killifish CFTR (kfCFTR) in chloride cells of fresh water (FW) adapted
      fish and animals transferred to sea water (SW) for 24h, 48h and 14+ days.
      Confocal microscopy allowed localization within mitochondria-rich (MR) cells to
      be determined as superficial (i.e. in the apical membrane) or deeper within the
      cytoplasm of the cells. In FW, 90 % of MR cells had diffuse kfCFTR
      immunofluorescence in the central part of the cytosol, with only 8.1 % having
      apical kfCFTR, which was 6.6+/-0.54 microm below the microridges of surrounding
      pavement cells. Curiously, FW but not SW pavement cells also had positive
      immunofluorescence to kfCFTR. After 24h in SW, a time when kfCFTR expression is
      elevated, a condensed punctate immunofluorescence appeared among 18.8 % of MR
      cells, 13.4+/-0.66 microm (mean +/- S.E.M.) below the surface of the cells. By
      48h, a majority (76.3 %) of MR cells had punctate kfCFTR distribution and the
      distance from the surface was less (7.8+/-0.2 microm), a distribution approaching
      the SW-acclimated condition (i.e. all MR cells showing kfCFTR immunofluorescence,
      6.1+/-0.04 microm below the surface). In contrast, NKCC immunofluorescence was
      condensed and localized in lateral parts of MR cell complexes in FW animals and
      then redistributed to the whole basal cytoplasm after acclimation to SW. CFTR,
      the anion channel responsible for Cl(-) secretion in marine teleosts,
      redistributes in MR cells during SW acclimation by condensation of a diffuse
      distribution below the apical crypt, followed by translocation and insertion in
      the apical membrane. NKCC, the cotransporter that translocates Cl(-) across the
      basolateral membrane, moves from an eccentric cytosolic location in FW to a
      diffuse basolateral localization in SW chloride cells.

PMID- 11948205
TI  - Song discrimination by male cicadas Cicada barbara lusitanica (Homoptera,
      Cicadidae).
AB  - Cicada barbara lusitanica males presented a stereotyped singing response
      behaviour when exposed to a playback of the conspecific song. Males preferred (as
      measured by the time taken to sing) the conspecific signal to heterospecific
      songs that differed markedly in temporal pattern. Manipulation of the gross
      temporal pattern of C. barbara calling song significantly reduced stimulus
      attractiveness. Indeed, C. barbara males stopped responding to stimuli in which
      the temporal pattern approached the characteristic C. orni song, a sympatric and
      closely related species. If present in females, the preference for stimuli with
      pauses not exceeding 30 ms could reflect the evolution of a behavioural pre
      copulatory isolating mechanism based on song analysis. Males discriminated
      frequencies within 3-15 kHz, clearly preferring 6 and 9 kHz; both these
      frequencies matched the main spectral peaks of the song. The preference for
      specific frequencies was not associated with maximum neuronal excitation as
      estimated by auditory nerve recordings, which suggests that this frequency
      dependent behaviour is not based on the strength of the auditory system's
      response to different frequencies. Rather, it is likely to reflect fine frequency
      resolution in the central nervous system.

PMID- 11948206
TI  - Temperature adaptation in Gillichthys (Teleost: Gobiidae) A(4)-lactate
      dehydrogenases: identical primary structures produce subtly different
      conformations.
AB  - Alternative conformations of proteins underlie a variety of biological phenomena,
      from prion proteins that cause spongiform encephalopathies to membrane channel
      proteins whose conformational changes admit or exclude specific ions. In this
      paper, we argue that conformational differences within globular 'housekeeping'
      enzymes may allow rapid adaptation to novel environments. Muscle-type lactate
      dehydrogenases (A(4)-LDHs) from the gobies Gillichthys seta and G. mirabilis have
      identical amino acid sequences but show potentially adaptive differences in
      substrate affinity (apparent Michaelis constants for pyruvate, K(m)(PYR)) as well
      as differences in thermal stability. We examined the A(4)-LDH of each species
      using fluorescence spectroscopy, near- and far-ultraviolet circular dichroism
      (CD) spectroscopy and hydrogen/deuterium exchange (H/D) Fourier-transform
      infrared spectroscopy to determine whether structural differences were apparent,
      the extent to which structural differences could be related to differences in
      conformational flexibility and whether specific changes in secondary or tertiary
      structure could be defined. The fluorescence spectra and far-ultraviolet CD
      spectra of the A(4)-LDH from the two species were indistinguishable, suggesting
      that the two conformations are very similar in secondary and tertiary structure.
      Apparent melting temperatures (T(m)) followed by fluorescence and CD spectroscopy
      confirmed that the G. mirabilis A(4)-LDH is more thermally stable than the G.
      seta form. H/D exchange kinetics of Gillichthys A(4)-LDH was described using
      double-exponential regression; at 20 degrees C, G. seta A(4)-LDH has a higher
      exchange constant, indicating a more flexible and open structure. At 40 degrees
      C, the difference in H/D exchange constants disappears. Second-derivative
      analysis of H/D exchange infrared spectra indicates that alpha-helical, but not
      beta-sheet structure, differs in conformational flexibility between the two
      forms. Second-derivative ultraviolet spectra indicate that at least one of the
      five tyrosyl residues in the Gillichthys LDH-A monomer is located in a more
      hydrophobic environment in the G. mirabilis form. Homology models of A(4)-LDH
      indicate that Tyr246 is the most likely candidate to experience a modified
      environment because it is involved in subunit contacts within the homotetramer
      and sits in a hinge between a static alpha-helix and one involved in catalytic
      conformational changes. Subtle differences in conformation around this residue
      probably play a role both in altered flexibility and in the potentially adaptive
      differences in kinetics between the two A(4)-LDH forms.

PMID- 11948207
TI  - Serotonin sets the day state in the neurons that control coupling between the
      optic lobe circadian pacemakers in the cricket Gryllus bimaculatus.
AB  - The bilaterally paired optic lobe circadian pacemakers of the cricket Gryllus
      bimaculatus mutually exchange photic and circadian information to keep their
      activity synchronized. The information is mediated by a neural pathway,
      consisting of the so-called medulla bilateral neurons, connecting the medulla
      areas of the two optic lobes. We investigated the effects of serotonin on the
      neural activity in this coupling pathway. Spontaneous and light-induced
      electrical activity of the neurons in the coupling pathway showed daily
      variations, being more intense during the night than the day. Microinjection of
      serotonin or a serotonin-receptor agonist, quipazine, into the optic lobe caused
      a dose- and time-dependent inhibition of spontaneous and light-induced responses,
      mimicking the day state. The amount of suppression was greater and the recovery
      from the suppression occurred faster during the night. Application of
      metergoline, a non-selective serotonin-receptor antagonist, increased spontaneous
      activity and light-evoked responses during both the day and the night, with
      higher effect during the day. In addition, metergoline effectively attenuated the
      effects of serotonin. These facts suggest that in the cricket's optic lobe,
      serotonin is released during the daytime and sets the day state in the neurons
      regulating coupling between the bilaterally paired optic lobe circadian
      pacemakers.

PMID- 11948209
TI  - Torque patterns of the limbs of small therian mammals during locomotion on flat
      ground.
AB  - In three species of small therian mammals (Scandentia: Tupaia glis, Rodentia:
      Galea musteloides and Lagomorpha: Ochotona rufescens) the net joint forces and
      torques acting during stance phase in the four kinematically relevant joints of
      the forelimbs (scapular pivot, shoulder joint, elbow joint, wrist joint) and the
      hindlimbs (hip joint, knee joint, ankle joint, intratarsal joint) were determined
      by inverse dynamic analysis. Kinematics were measured by cineradiography (150
      frames s(-1)). Synchronously ground reaction forces were acquired by forceplates.
      Morphometry of the extremities was performed by a scanning method using
      structured illumination. The vector sum of ground reaction forces and weight
      accounts for most of the joint force vector. Inertial effects can be neglected
      since errors of net joint forces amount at most to 10 %. The general time course
      of joint torques is comparable for all species in all joints of the forelimb and
      in the ankle joint. Torques in the intratarsal joints differ between tailed and
      tail-less species. The torque patterns in the knee and hip joint are unique to
      each species. For the first time torque patterns are described completely for the
      forelimb including the scapula as the dominant propulsive segment. The results
      are compared with the few torque data available for various joints of cats (Felis
      catus), dogs (Canis lupus f. familiaris), goats (Capra sp.) and horses (Equus
      przewalskii f. caballus).

PMID- 11948208
TI  - Basic limb kinematics of small therian mammals.
AB  - A comparative study of quantitative kinematic data of fore- and hindlimb
      movements of eight different mammalian species leads to the recognition of basic
      principles in the locomotion of small therians. The description of kinematics
      comprises fore- and hindlimb movements as well as sagittal spine movements
      including displacement patterns of limb segments, their contribution to step
      length, and joint movements. The comparison of the contributions of different
      segments to step length clearly shows the proximal parts (scapula, femur) to
      produce more than half of the propulsive movement of the whole limb at
      symmetrical gaits. Basically, a three-segmented limb with zigzag configuration of
      segments is mainly displaced at the scapular pivot or hip joint, both of which
      have the same vertical distance to the ground. Two segments operate in matched
      motion during retraction of the limb. While kinematic parameters of forelimbs are
      independent of speed and gait (with the scapula as the dominant element),
      fundamental changes occur in hindlimb kinematics with the change from symmetrical
      to in-phase gaits. Forward motion of the hindlimbs is now mainly due to sagittal
      lumbar spine movements contributing to half of the step length. Kinematics of
      small therian mammals are independent of their systematic position, their natural
      habitat, and also of specific anatomical dispositions (e.g. reduction of fingers,
      toes, or clavicle). In contrast, the possession of a tail influences 'pelvic
      movements'.

PMID- 11948210
TI  - Primate evolutionary genetics.

PMID- 11948211
TI  - Analysis of the complete human mtDNA genome: methodology and inferences for human
      evolution.
AB  - The analysis of mitochondrial DNA (mtDNA) sequences has been a potent tool in our
      understanding of human evolution. However, almost all studies of human evolution
      based on mtDNA sequencing have focused on the control region, which constitutes
      less than 7% of the mitochondrial genome. The rapid development of technology for
      automated DNA sequencing has made it possible to study the complete mtDNA genomes
      in large numbers of individuals, opening the field of mitochondrial population
      genomics. Here we describe a suitable methodology for determining the complete
      human mitochondrial sequence and the global mtDNA diversity in humans. Also, we
      discuss the implications of the results with respect to the different hypotheses
      for the evolution of modern humans.

PMID- 11948212
TI  - Divergent origins and concerted expansion of two segmental duplications on
      chromosome 16.
AB  - An unexpected finding of the human genome was the large fraction of the genome
      organized as blocks of interspersed duplicated sequence. We provide a comparative
      and phylogenetic analysis of a highly duplicated region of 16p12.2, which is
      composed of at least four different segmental duplications spanning in excess of
      160 kb. We contrast the dispersal of two different segmental duplications (LCR16a
      and LCR16u). LCR16a, a 20 kb low-copy repeat sequence A from chromosome 16, was
      shown previously to contain a rapidly evolving novel hominoid gene family
      (morpheus) that had expanded within the last 10 million years of great ape/human
      evolution. We compare the dispersal of this genomic segment with a second
      adjacent duplication called LCR16u. The duplication contains a second putative
      gene family (KIAA0220/SMG1) that is represented approximately eight times within
      the human genome. A high degree of sequence identity (approximately 98%) was
      observed among the various copies of LCR16u. Comparative analyses with Old World
      monkey species show that LCR16a and LCR16u originated from two distinct ancestral
      loci. Within the human genome, at least 70% of the LCR16u copies were duplicated
      in concert with the LCR16a duplication. In contrast, only 30% of the chimpanzee
      loci show an association between LCR16a and LCR16u duplications. The data suggest
      that the two copies of genomic sequence were brought together during the
      chimpanzee/human divergence and were subsequently duplicated as a larger cassette
      specifically within the human lineage. The evolutionary history of these two
      chromosome-specific duplications supports a model of rapid expansion and
      evolutionary turnover among the genomes of man and the great apes.

PMID- 11948213
TI  - Human and ape molecular clocks and constraints on paleontological hypotheses.
AB  - Although the relationships of the living hominoid primates (humans and apes) are
      well known, the relationships of the fossil species, times of divergence of both
      living and fossil species, and the biogeographic history of hominoids are not
      well established. Divergence times of living species, estimated from molecular
      clocks, have the potential to constrain hypotheses of the relationships of fossil
      species. In this study, new DNA sequences from nine protein-coding nuclear genes
      in great apes are added to existing datasets to increase the precision of
      molecular time estimates bearing on the evolutionary history of apes and humans.
      The divergence of Old World monkeys and hominoids at the Oligocene-Miocene
      boundary (approximately 23 million years ago) provides the best primate
      calibration point and yields a time and 95% confidence interval of 5.4 +/- 1.1
      million years ago (36 nuclear genes) for the human-chimpanzee divergence. Older
      splitting events are estimated as 6.4 +/- 1.5 million years ago (gorilla, 31
      genes), 11.3 +/- 1.3 million years ago (orangutan, 33 genes), and 14.9 +/- 2.0
      million years ago (gibbon, 27 genes). Based on these molecular constraints, we
      find that several proposed phylogenies of fossil hominoid taxa are unlikely to be
      correct.

PMID- 11948214
TI  - Modern African ape populations as genetic and demographic models of the last
      common ancestor of humans, chimpanzees, and gorillas.
AB  - In order to fully understand human evolutionary history through the use of
      molecular data, it is essential to include our closest relatives as a comparison.
      We provide here estimates of nucleotide diversity and effective population size
      of modern African ape species using data from several independent noncoding
      nuclear loci, and use these estimates to make predictions about the nature of the
      ancestral population that eventually gave rise to the living species of African
      apes, including humans. Chimpanzees, bonobos, and gorillas possess two to three
      times more nucleotide diversity than modern humans. We hypothesize that the last
      common ancestor (LCA) of these species had an effective population size more
      similar to modern apes than modern humans. In addition, estimated dates for the
      divergence of the Homo, Pan, and Gorilla lineages suggest that the LCA may have
      had stronger geographic structuring to its mtDNA than its nuclear DNA, perhaps
      indicative of strong female philopatry or a dispersal system analogous to
      gorillas, where females disperse only short distances from their natal group.
      Synthesizing different classes of data, and the inferences drawn from them,
      allows us to predict some of the genetic and demographic properties of the LCA of
      humans, chimpanzees, and gorillas.

PMID- 11948215
TI  - Genomic divergence between human and chimpanzee estimated from large-scale
      alignments of genomic sequences.
AB  - To study the genomic divergence between human and chimpanzee, large-scale genomic
      sequence alignments were performed. The genomic sequences of human and chimpanzee
      were first masked with the RepeatMasker and the repeats were excluded before
      alignments. The repeats were then reinserted into the alignments of nonrepetitive
      segments and entire sequences were aligned again. A total of 2.3 million base
      pairs (Mb) of genomic sequences, including repeats, were aligned and the average
      nucleotide divergence was estimated to be 1.22%. The Jukes-Cantor (JC) distances
      (nucleotide divergences) in nonrepetitive (1.44 Mb) and repetitive sequences
      (0.86 Mb) are 1.14% and 1.34%, respectively, suggesting a slightly higher average
      rate in repetitive sequences. Annotated coding and noncoding regions of
      homologous chimpanzee genes were also retrieved from GenBank and compared. The
      average synonymous and nonsynonymous divergences in 88 coding genes are 1.48% and
      0.55%, respectively. The JC distances in intron, 5' flanking, 3' flanking,
      promoter, and pseudogene regions are 1.47%, 1.41%, 1.68%, 0.75%, and 1.39%,
      respectively. It is not clear why the genetic distances in most of these regions
      are somewhat higher than those in genomic sequences. One possible explanation is
      that some of the genes may be located in regions with higher mutation rates.

PMID- 11948216
TI  - Mitochondrial 16S rRNA sequence diversity of hominoids.
AB  - We determined nucleotide sequences of the 16S rRNA gene of mitochondrial DNA
      (mtDNA) (about 1.6 kb) for 35 chimpanzee, 13 bonobo, 10 gorilla, 16 orangutan,
      and 23 gibbon individuals. We compared those data with published sequences and
      estimated nucleotide diversity for each species. All the ape species showed
      higher diversity than human. We also constructed phylogenetic trees and networks.
      The two orangutan subspecies were clearly separated from each other, and Sumatran
      orangutans showed much higher nucleotide diversity than Bornean orangutans. Some
      gibbon species did not form monophyletic clusters, and variation within species
      was not much different from that among species in the subgenus Hylobates.

PMID- 11948217
TI  - Determinants of effective population size for loci with different modes of
      inheritance.
AB  - Here we report an assessment of the determinants of effective population size
      (N(e)) in species with overlapping generations. Specifically, we used a
      stochastic demographic model to investigate the influence of different life
      history variables on N(e)/N (where N = population census number) and the
      influence of sex differences in life-history variables on N(e) for loci with
      different modes of inheritance. We applied an individual-based modeling approach
      to two datasets: one from a natural population of savannah baboons (Papio
      cynocephalus) in the Amboseli basin of southern Kenya and one from a human tribal
      population (the Gainj of Papua New Guinea). Simulation-based estimates of N(e)/N
      averaged 0.329 for the Amboseli baboon population (SD = 0.116, 95% CI = 0.172 -
      0.537) and 0.786 for the Gainj (SD = 0.184, 95% CI = 0.498 - 1.115). Although
      variance in male fitness had a substantial impact on N(e)/N in each of the two
      primate populations, ratios of N(e) values for autosomal and sex-linked loci
      exhibited no significant departures from Poisson-expected values. In each case,
      similarities in sex-specific N(e) values were attributable to the unexpectedly
      high variance in female fitness. Variance in male fitness resulted primarily from
      age-dependent variance in reproductive success, whereas variance in female
      fitness resulted primarily from stochastic variance in survival during the
      reproductive phase.

PMID- 11948218
TI  - Mitochondrial DNA variation in benzimidazole-resistant and -susceptible
      populations of the small ruminant parasite Teladorsagia circumcincta.
AB  - The genetic diversity of the mtDNA ND4 gene in 11 Teladorsagia circumcincta
      populations from France and Morocco was assessed by sequencing. Some of these
      nematode populations were resistant to benzimidazole (BZ) anthelmintics, while
      others were susceptible. The nucleotide diversity in all populations studied was
      very high, probably due to a high mutation rate in nematodes, but there was no
      significant difference between them. This suggests that no strong, recurrent
      bottlenecks occur during the acquisition of BZ resistance by a worm population.
      The conservation of genetic variations during the acquisition of BZ resistance is
      probably due to the fact that anthelmintic treatments do not kill all the
      susceptible adult worms and to the presence of numerous free-living larvae that
      are not submitted to this anthelmintic pressure. There was no genetic subdivision
      between worm populations on a small geographical scale (less than 200 km), but
      significant F(ST)s were found on a larger geographical scale. This kind of
      subdivision cannot be explained by different genetic flows between populations
      because all these populations were isolated from each other. This subdivision is
      probably due to the breeding management practices and the large size of these
      worm populations, which limit genetic drift.

PMID- 11948219
TI  - Inheritance of the chloroplast genome in Sorbus aucuparia L. (Rosaceae).
AB  - Chloroplast DNA (cpDNA) inheritance was investigated in Sorbus aucuparia using
      progenies obtained from six controlled crosses between individuals of known
      haplotype. Polymerase chain reaction (PCR) amplification, followed by restriction
      analysis, was used to characterize 248 offspring for either of two polymorphic
      cpDNA fragments. All offspring exhibited the maternal haplotype, which indicates
      maternal inheritance of chloroplasts in S. aucuparia. Power analysis of the test
      showed that the frequency of paternal transmission of chloroplasts, if any,
      should not exceed 1.84% (with 99% confidence).

PMID- 11948220
TI  - Linkage between loci controlling nodulation and testa variegation in peanut.
AB  - Linkage of loci controlling nodulation (N(1)) and testa variegation (V) was
      studied for cultivated peanut (Arachis hypogaea L.). The lines M4-2
      (nonnodulating, variegated; VVn(1)n(1)n(2)n(2)N(3)N(3)) and UF 487A (nodulating,
      nonvariegated; vvN(1)N(1)n(2)n(2)N(3)N(3)) were used as parents in the crosses M4
      2 x UF 487A, M4-2 x (UF 487A x M4-2), and their reciprocals. Individual plants
      were evaluated for nodulation and testa variegation in the F(1), F(2), F(3),
      F(1)BC(1), and F(2)BC(1) generations. Data indicate that the N(1) and V loci are
      linked with calculated crossover percentage of 7.1%.

PMID- 11948222
TI  - A radiation hybrid mapping panel for the rhesus macaque.
AB  - The genomes of nonhuman primates have recently become highly visible candidates
      for full genome analysis, as they provide powerful models of human disease and a
      better understanding of the evolution of the human genome. We describe the
      creation of a 5000 rad radiation hybrid (RH) mapping panel for the rhesus
      macaque. Duplicate genotypes of 84 microsatellite and coding gene sequence tagged
      sites from six macaque chromosomes produced an estimated whole genome retention
      frequency of 0.33. To test the mapping ability of the panel, we constructed RH
      maps for macaque chromosomes 7 and 9 and compared them to orthologous locus
      orders in existing human and baboon maps derived from different methodologies.
      Concordant marker order between all three species maps suggests that the current
      panel represents a powerful mapping resource for generating high-density
      comparative maps of the rhesus macaque and other species genomes.

PMID- 11948221
TI  - High levels of genetic differentiation of Oryza officinalis Wall. ex Watt. from
      China.
AB  - In order to determine the population genetic structure of wild rice (Oryza
      officinalis Wall. ex Watt.), an endangered tropical and subtropical species,
      allozyme diversity encoded by 24 loci was analyzed electrophoretically in 145
      individuals of eight natural populations from Hainan, Guangxi, and Yunnan
      provinces, China. A fairly high genetic differentiation (F(ST) = 0.882 and mean I
      = 0.786) was found among the studied populations. Our results suggest that
      restricted gene flow may play a significant role in shaping such a population
      genetic structure. In addition, high genetic differentiation among populations
      within a geographically limited region may stem from a reduced population size
      and consequent genetic drift.

PMID- 11948223
TI  - Partial cytochrome b sequences for six Hymenoptera of the eastern United States.
AB  - Mitochondrial DNA (mtDNA) haplotypes have been commonly used to determine
      honeybee subspecies relationships. To see if these markers would also be useful
      for comparisons of other Hymenoptera, we collected workers of six local species:
      Vespa crabro, the European hornet; Bombus impatiens, a bumblebee; Vespula
      germanica, the German yellow jacket; Polistes fuscatus, a paper wasp; Halictus
      ligatus, an alkali bee; and an unspecified Megachile, a leafcutting bee. MtDNA
      was isolated and digested with six endonucleases (AvaI, BglII, EcoRI, HindIII,
      HinfI, XbaI). The digested DNA was electrophoresed and visualized on agarose gels
      with comparison to a standard fragment marker and similarly treated honeybee
      mtDNA. The fragments obtained were also purified and sequenced. Phylogenetic
      relationships between six wasp and bee species, Apis mellifera, and several other
      similar aculeate Hymenoptera were determined. Newly defined DNA sequences were
      posted to GenBank (AF281169-AF281174).

PMID- 11948224
TI  - Inheritance of the general shell color in the scallop Argopecten purpuratus
      (Bivalvia: Pectinidae).
AB  - Although some external coloration and pigmentation patterns in molluscan shells
      may be attributable to environmental factors, most variation in these phenotypic
      characters depends on uncomplicated genetic mechanisms. Genetic research on
      inheritance of color variations in the north-Chilean scallop (Argopecten
      purpuratus) has now been expanded to analyze color segregation in juvenile
      scallops produced under controlled conditions employing self- and cross
      fertilization. Calculations from the results were used for comparison with
      different numerical models based on Mendelian inheritance, and results were also
      obtained on the inheritance of a dorsoventral white line often observed on the
      left (upper) valve in this species. The results confirmed the hereditary basis
      for color variation in the shell of this scallop, suggesting a simple, dominant
      model of epistasis to explain the distribution of the different color variants
      observed (purple, brown, orange, yellow, and white). The presence of the white
      line may be controlled by a recessive allele with simple Mendelian traits on a
      locus distinct from those that control color variation.

PMID- 11948226
TI  - CEA doubling time and CEA half-life in the prediction of recurrences after
      colorectal cancer surgery.

PMID- 11948227
TI  - Phase I/II study of 3-week cycle cisplatin-gemcitabine in advanced non-small cell
      lung cancer.
AB  - BACKGROUND: The combination of cisplatin and gemcitabine is one of the most
      active chemotherapy regimens against non-small cell lung cancer. However, the
      optimum schedule for this combination has not been determined. This study was
      performed to determine the maximum tolerated dose of gemcitabine combined with
      cisplatin in a 3-week cycle regimen and to observe safety and efficacy for
      Japanese patients with advanced non-small cell lung cancer. METHODS: 80 mg/m(2)
      of cisplatin on day 1 and escalated doses of gemcitabine on days 1 and 8 were
      administered every 3 weeks to patients with previously untreated, advanced non
      small cell lung cancer. The initial dose of gemcitabine was 1000 mg/m(2) and was
      escalated in 250 mg/m(2) increments. RESULTS: Twenty-four patients were enrolled
      between March and December 2000. In total, 64 courses were given. The main
      toxicities were neutropenia, thrombocytopenia and hepatotoxicity. The maximum
      tolerated dose was determined to be 1500 mg/m(2) of gemcitabine combined with 80
      mg/m(2 )of cisplatin. Nine of 24 patients (37.5%) achieved a partial response.
      CONCLUSION: This study demonstrates that the combination of cisplatin and
      gemcitabine repeated every three weeks is tolerable for Japanese patients with
      advanced non-small cell lung cancer. We determined 1250 mg/m(2) of gemcitabine
      combined with 80 mg/m(2 )of cisplatin to be the recommended dose.

PMID- 11948228
TI  - A feasibility study of paclitaxel 225 mg/m(2) and carboplatin AUC = 6 in
      untreated advanced non-small cell lung cancer patients in Japan.
AB  - BACKGROUND: The combination of paclitaxel (225 mg/m(2), 3 h infusion) and
      carboplatin [area under the curve (AUC) 6 mg/ml x min] is used widely for non
      small cell lung cancer in the USA and is one of the standard regimens in the
      Southwest Oncology Group. In Japan, however, the upper limit of the approved dose
      for single-use paclitaxel is 210 mg/m(2) and the optimum dose of this agent in
      combination with carboplatin has not yet been established. This study was
      designated to determine whether the paclitaxel dose of 225 mg/m(2 ) plus
      carboplatin (AUC = 6) is tolerable for Japanese patients with untreated advanced
      non-small cell lung cancer. METHODS: Ten patients were enrolled between October
      1999 and June 2000 and all of these patients were evaluable for toxicity.
      Chemotherapy consisted of carboplatin (AUC = 6 mg/ml x min) and 225 mg/m(2 )of
      paclitaxel on day 1 every 3 weeks. RESULTS: Neutropenia was the major toxicity
      and grade 4 neutropenia was observed in seven of the 10 patients (70%), but
      febrile neutropenia was not observed. Grade 4 anemia as a dose-limiting toxicity
      was observed in two patients. This was due to gastric ulcer bleeding in both
      patients. Only one patient experienced grade 3 peripheral neuropathy. No grade 3
      or more myalgia or arthralgia was reported. Overall, 44 courses of chemotherapy
      were administered in 10 patients. Partial responses were observed in six of the
      10 patients (60%). Median survival time was 7.7 months. CONCLUSION: Paclitaxel at
      225 mg/m(2) in a 3 h infusion and carboplatin AUC = 6 appears to be tolerable in
      Japanese patients with untreated advanced non-small cell lung cancer.

PMID- 11948229
TI  - Usefulness of analytical CEA doubling time and half-life time for overlooked
      synchronous metastases in colorectal carcinoma.
AB  - BACKGROUND: Measurement of carcinoembryonic antigen (CEA) has been widely applied
      to detect recurrence, especially of colorectal carcinoma. The validity however,
      is still controversial. We investigated serial changes in CEA values to calculate
      whether the CEA doubling time and half-life time could predict metastatic
      progression or prognosis in colorectal carcinoma. METHODS: Pre- and post
      operative serial serum CEA contents were determined in 22 cases of colorectal
      cancer with or without metastasis. CEA values were determined by enzyme
      immunoassay (EIA). Patients were assigned depending upon survival time (within
      vs. more than 18 months after primary resection) for assessment of CEA doubling
      time. From the gradient of the semi-logarithmic CEA graph, the preoperative
      doubling time was calculated and the postoperative half-life time was estimated
      according to the diagnosis of metastases within 2 years after primary resection
      [metastasis (+) or (-)]. RESULTS: In spite of the effect of curative re-operation
      of metastatic lesions or of postoperative adjuvant chemotherapy, the CEA doubling
      time of the groups showed a relation with prognosis (p = 0.045, Student's t-test)
      when the patients were divided into >18 and < or =18 months survival time. The
      CEA half-life time of the groups without overlooked metastases was statistically
      longer than those with (mean +/- SD 8.01 +/- 2.07 and 4.33 +/- 1.11,
      respectively, p < 0.01, one-factor ANOVA test). Clearance (k) showed a
      significant difference between the groups (p < 0.001, Student's t-test).
      CONCLUSION: The CEA doubling time appeared to be a less independent prognostic
      factor, whereas prolongation of the CEA half-life time might potentially suggest
      the existence of overlooked synchronous metastases from colorectal carcinoma.

PMID- 11948230
TI  - Advanced esophageal cancer with esophago-bronchial fistula successfully treated
      by chemoradiation therapy with additional endoscopic resection: a case report.
AB  - Chemoradiation is potentially curative for esophageal cancer in various stages,
      but local failure is a major problem. The present case was a 49-year-old male
      diagnosed with advanced esophageal cancer with an esophago-bronchial fistula and
      lymph node metastasis. Histological diagnosis by biopsy was adenosquamous cell
      carcinoma. Chemoradiotherapy comprising intravenous infusion of cisplatin and
      continuous infusion of 5-fluorouracil with concurrent radiation was initiated in
      July 1997. In December 1997, after four courses of therapy, partial remission was
      obtained and the fistula closed with a remnant polypoid lesion at the primary
      site, which remained even after six courses of treatment. In February 1998,
      endoscopic polypectomy was performed for the remnant lesion and histological
      examination revealed that it contained adenocarcinoma cells. Thereafter, no
      additional treatment was performed and the patient has been disease-free for 3.5
      years. This case suggests that additional endoscopic resection is an optional
      treatment for local failure after chemoradiation.

PMID- 11948231
TI  - Locally advanced mucinous carcinoma of the breast with sudden growth
      acceleration: a case report.
AB  - We report a 35-year-old woman with locally advanced mucinous carcinoma of the
      breast with sudden growth acceleration. A pea-sized mass developed into an
      ulcerated large tumor within 1 month. After the combination of chemotherapy,
      radiation and hyperthermia, a radical mastectomy was performed, followed by
      repair of the skin defect by latissimus dorsi and rectus abdominis
      musculocutaneous flaps. Histological examination revealed a pure mucinous
      carcinoma with axillary lymph node involvement. Estrogen and progesterone
      receptors were not detected in the tumor. Twenty-five months after treatment,
      there is no sign of recurrent disease. Pure mucinous carcinoma generally has a
      less aggressive growth pattern as defined by tumor size, adherence to the
      overlying skin/bottom fasciae, estrogen and progesterone receptor positive and
      primary lymph axillary lymph node metastases. This case showed completely
      opposite features to all of these typical biological features of pure mucinous
      carcinomas.

PMID- 11948232
TI  - Occlusion of the left superficial femoral artery during hepatic arterial infusion
      of chemotherapy for liver metastases from colon cancer 18 months after the
      implantation of a port system: a case report.
AB  - We report a case of complication of a catheter port system. A 67-year-old male
      who had undergone left hemicolorectomy and partial hepatectomy for liver
      metastases from colon cancer underwent hepatic arterial infusion (HAI) of
      chemotherapy by a percutaneously implanted catheter port system to prevent
      recurrence. Eighteen months after the implantation of a port system he complained
      of intermittent claudication. Intravenous digital subtraction angiography (IV
      DSA) showed occlusion of the left superficial femoral artery. The catheter was
      removed and a femoro-popliteal bypass with an artificial graft was constructed.
      Thrombus was found around the indwelling catheter at the insertion site. After
      the operation his complaint disappeared and has been alive without recurrence for
      6 years.

PMID- 11948233
TI  - Spontaneous regression of metastatic endometrial stromal sarcoma.
AB  - Spontaneous regression of malignancy is rare and there appear to be no reports of
      spontaneous regression of endometrial stromal sarcoma. We report a rare case of
      metastatic endometrial stromal sarcoma that regressed spontaneously. A 58-year
      old woman was admitted to hospital in January 1996 when her chest radiograph
      showed multiple nodular shadows in the left lower lung field. Computed tomography
      of the chest revealed bilateral nodules. Segmentectomy of the left lower lobe was
      performed by thoracoscopy. She had a past history of uterine myoma with
      metrorrhagia for which she had undergone a hystero-oophorectomy 10 years earlier.
      She also had a vaginal polyp removed 1 year earlier. The lung pathology was
      studied and the surgical specimens of the uterus and vagina were re-examined. The
      diagnosis was endometrial stromal sarcoma primarily arising in the uterus. The
      vaginal polyp and the pulmonary nodules were considered to be metastases. Samples
      of lung and vaginal tissues were positive for both estrogen and progesterone
      receptors. The patient was discharged without treatment in February 1996 and
      followed up in the outpatient clinic. The tumor shadow measuring 2 mm in diameter
      on admission was enlarged to 4 mm in diameter 1 year later. Surprisingly,
      spontaneous regression of the lung disease occurred at 33 months, the tumor size
      decreasing to 2 mm in diameter and to 1 mm at 46 months. No evidence of tumor
      enlargement was detected at the last follow-up in July 2001. Although the precise
      mechanism of tumor regression is unknown, metastatic endometrial stromal sarcoma
      may spontaneously regress.

PMID- 11948234
TI  - A role for CO(2) and bicarbonate transporters in metabolic exchanges in the
      brain.
AB  - Acid-base transporters are linked to the energy metabolism via the end product of
      oxidative metabolism, carbon dioxide, together with carbonic anhydrase activity.
      In a tissue such as the brain, where some cells (neurones) are high-energy
      consumers when active, and other cells (astroglial cells) are destined for
      homeostatic and trophic tasks, transport systems may complement each other and
      cooperate in order to maintain physiological functions. Here, some aspects of the
      coupling of metabolite shuttling and acid/base-dependent transport in neurones
      and glial cells are discussed.

PMID- 11948235
TI  - Refsum's disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation.
AB  - Refsum's disease (hereditary motor sensory neuropathy type IV, heredopathia
      atactica polyneuritiformis) is an autosomal recessive disorder the clinical
      features of which include retinitis pigmentosa, blindness, anosmia, deafness,
      sensory neuropathy, ataxia and accumulation of phytanic acid in plasma- and lipid
      containing tissues. The transport and biochemical pathways of phytanic acid
      metabolism have recently been defined with the cloning of two key enzymes,
      phytanoyl-CoA 2-hydroxylase (PAHX) and 2-hydroxyphytanoyl-CoA lyase, together
      with the confirmation of their localization in peroxisomes. PAHX, an iron(II) and
      2-oxoglutarate-dependent oxygenase is located on chromosome 10p13. Mutant forms
      of PAHX have been shown to be responsible for some, but not all, cases of
      Refsum's disease. Certain cases have been shown to be atypical mild variants of
      rhizomelic chondrodysplasia punctata type 1a. Other atypical cases with low
      plasma phytanic acid may be caused by alpha-methylacyl-CoA racemase deficiency. A
      sterol-carrier protein-2 (SCP-2) knockout mouse model shares a similar clinical
      phenotype to Refsum's disease, but no mutations in SCP-2 have been described to
      date in man. This review describes the clinical, biochemical and metabolic
      features of Refsum's disease and shows how the biochemistry of the alpha
      oxidation pathway may be linked to the regulation of metabolic pathways
      controlled by isoprenoid lipids, involving calcineurin or the peroxisomal
      proliferator activating alpha-receptor.

PMID- 11948236
TI  - Molecular determinants for the differential coupling of Galpha(16) to the
      melatonin MT1, MT2 and Xenopus Mel1c receptors.
AB  - The pineal neurohormone melatonin modulates a variety of physiological processes
      through different receptors. It has recently been reported that the cloned
      melatonin receptors (MT1, MT2 and Mel1c) exhibit differential abilities to
      stimulate phospholipase C (PLC) via G(16). Here we examined the molecular basis
      of such differences in melatonin receptor signaling. Coexpression of MT1 or MT2
      with the alpha subunit of G(16) (Galpha(16) ) allowed COS-7 cells to accumulate
      inositol phosphates in response to 2-iodomelatonin. In contrast, Mel1c did not
      activate Galpha(16) even though its expression was demonstrated by radioligand
      binding and agonist-induced inhibition of adenylyl cyclase. As Mel1c possesses an
      exceptionally large C-terminal tail, we further asked if this structural feature
      prevented productive coupling to Galpha(16). Eleven chimeric melatonin or mutant
      receptors were constructed by swapping all or part of the C-terminal tail between
      MT1, MT2 and Mel1c. All chimeras were fully capable of binding 2-[(125)
      I]iodomelatonin and inhibiting adenylyl cyclase. Chimeras containing the full
      length Mel1c tail were incapable of activating Galpha(16), while those that
      contained the complete C-terminal region of either MT1 or MT2 stimulated PLC.
      Incorporation of the extra portion of the C-terminal tail of Mel1c to either MT1
      or MT2 completely abolished the chimeras' ability to stimulate PLC via
      Galpha(16). In contrast, truncation of the C-terminal tail of Mel1c allowed
      interaction with Galpha(16). Our results suggest that Galpha(16) can discern
      structural differences amid the three melatonin receptors and provide evidence
      for functional distinction of Mel1c from MT1 and MT2 receptors.

PMID- 11948237
TI  - Protease-activated receptor-2 (PAR-2) in brain microvascular endothelium and its
      regulation by plasmin and elastase.
AB  - Protease-activated receptors (PARs) mediate cell activation after proteolytic
      cleavage of their extracellular amino terminus. We have reported earlier that
      primary cultures of rat brain capillary endothelial (RBCE) cells express at least
      two receptors for thrombin: PAR-1 and PAR-3. In the present study we show that
      PAR-2 activation by trypsin or by the PAR-2 agonist peptide (SLIGRL) evokes
      [Ca(2+) ](i) signal in RBCE cells. Taking advantage of RBCE cells expressing PAR
      1 and PAR-2, we show that trypsin activates both receptors. The relative agonist
      activity of trypsin and thrombin on PARs of RBCE cells compared with that of
      SLIGRL were 112% and 48%, respectively, whereas the potency of trypsin was 10(5) 
      fold higher than that of SLIGRL. Because under pathological conditions other
      proteases such as plasmin or leukocyte elastase may reach the cells of the blood
      brain barrier, we investigated the effect of these proteases on RBCE cells.
      Elastase evoked a small increase in [Ca(2+) ](i) but preincubation of cells with
      elastase dose-dependently reduced the trypsin-induced [Ca(2+) ](i) signal.
      Plasmin had a 30% inhibitory effect on the trypsin-induced response, and reduced
      the SLIGRL signal by 20%. It is concluded that PAR-2 is functional in brain
      capillary endothelium, and that the main fibrinolytic proteases, plasmin and
      elastase, may regulate PAR-2 signalling under pathological conditions.

PMID- 11948238
TI  - Identification of inhibitor-of-differentiation 2 (Id2) as a modulator of neuronal
      apoptosis.
AB  - Inhibitor-of-differentiation 2 (Id2) belongs to a family of transcriptional
      modulators that are characterized by a helix loop helix region but lack the basic
      amino acid domain. During development, Id2 antagonizes differentiation mediated
      by the retinoblastoma protein, probably by scavenging downstream E-box basic
      helix-loop-helix proteins. Here, using differential display RT-PCR, we identify
      Id2 as an induced gene during serum and potassium deprivation-induced apoptosis
      of cerebellar granule neurons. Consistent with a biological role for induced Id2
      messenger RNA and protein expression in neuronal cell death, expression of Id2
      antisense RNA, or targeted deletion of the Id2 gene in neurons from Id2 knock-out
      mice, protect from apoptosis. Further, gene transfer- mediated overexpression of
      Id2 induces neuronal cell death both in high potassium and low potassium
      conditions. Thus, the present study defines a role for Id2 in the modulation of
      neuronal apoptosis.

PMID- 11948239
TI  - Na,K-ATPase alpha3 subunit in the goldfish retina during optic nerve
      regeneration.
AB  - The goldfish optic nerve can regenerate after injury. To understand the molecular
      mechanism of optic nerve regrowth, we identified genes whose expression is
      specifically up-regulated during the early stage of optic nerve regeneration. A
      cDNA library constructed from goldfish retina 5 days after transection was
      screened by differential hybridization with cDNA probes derived from axotomized
      or normal retina. Of six cDNA clones isolated, one clone was identified as the
      Na,K-ATPase catalytic subunit alpha3 isoform by high- sequence homology. In
      northern hybridization, the expression level of the mRNA was significantly
      increased at 2 days and peaked at 5-10 days, and then gradually decreased and
      returned to control level by 45 days after optic nerve transection. Both in situ
      hybridization and immunohistochemical staining have revealed the location of this
      transient retinal change after optic nerve transection. The increased expression
      was observed only in the ganglion cell layer and optic nerve fiber layer at 5-20
      days after optic nerve transection. In an explant culture system, neurite
      outgrowth from the retina 7 days after optic nerve transection was spontaneously
      promoted. A low concentration of ouabain (50-100 nm ) completely blocked the
      spontaneous neurite outgrowth from the lesioned retina. Together, these data
      indicate that up-regulation of the Na,K-ATPase alpha3 subunit is involved in the
      regrowth of ganglion cell axons after axotomy.

PMID- 11948240
TI  - Diabetes-induced nitrative stress in the retina, and correction by
      aminoguanidine.
AB  - Aminoguanidine inhibits the development of retinopathy in diabetic animals, but
      the mechanism remains unclear. Inasmuch as aminoguanidine is a relatively
      selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), we
      have investigated the effects of hyperglycemia on the retinal nitric oxide (NO)
      pathway in the presence and absence of aminoguanidine. In vivo studies utilized
      retinas from experimentally diabetic rats treated or without aminoguanidine for 2
      months, and in vitro studies used bovine retinal endothelial cells and a
      transformed retinal glial cell line (rMC-1) incubated in 5 mm and 25 mm glucose
      with and without aminoguanidine (100 microg/mL). NO was detected as nitrite and
      nitrate, and nitrotyrosine and iNOS were detected using immunochemical methods.
      Retinal homogenates from diabetic animals had greater than normal levels of NO
      and iNOS (p < 0.05), and nitrotyrosine was greater than normal, especially in one
      band immunoprecipitated from retinal homogenates. Oral aminoguanidine
      significantly inhibited all of these increases. Nitrotyrosine was detected
      immunohistochemically only in the retinal vasculature of non-diabetic and
      diabetic animals. Retinal endothelial and rMC-1 cells cultured in high glucose
      increased NO and NT, and aminoguanidine inhibited both increases in rMC-1 cells,
      but only NT in endothelial cells. Hyperglycemia increases NO production in
      retinal cells, and aminoguanidine can inhibit this abnormality. Inhibition of
      diabetic retinopathy by aminoguanidine might be mediated in part by inhibition of
      sequelae of NO production.

PMID- 11948241
TI  - Generation of reactive oxygen species by the mitochondrial electron transport
      chain.
AB  - Generation of reactive oxygen species (ROS) by the mitochondrial electron
      transport chain (ETC), which is composed of four multiprotein complexes named
      complex I-IV, is believed to be important in the aging process and in the
      pathogenesis of neurodegenerative diseases such as Parkinson's disease. Previous
      studies have identified the ubiquinone of complex III and an unknown component of
      complex I as the major sites of ROS generation. Here we show that the
      physiologically relevant ROS generation supported by the complex II substrate
      succinate occurs at the flavin mononucleotide group (FMN) of complex I through
      reversed electron transfer, not at the ubiquinone of complex III as commonly
      believed. Indirect evidence indicates that the unknown ROS-generating site within
      complex I is also likely to be the FMN group. It is therefore suggested that the
      major physiologically and pathologically relevant ROS-generating site in
      mitochondria is limited to the FMN group of complex I. These new insights clarify
      an elusive target for intervening mitochondrial ROS-related processes or
      diseases.

PMID- 11948242
TI  - Effects of serotine receptors agonists, TFMPP and CGS12066B, on regional
      serotonin synthesis in the rat brain: an autoradiographic study.
AB  - The effects of acute and repeat administration of the serotonin (5-HT)(1)
      agonists TFMPP [N -(3-trifluoromethyl)phenylpiperazine hydrochloride] and
      CGS12066B [7-trifluoromethyl-4- (4-methyl-1-piperazinyl)pyrrolo[1,2-a ]
      quinoxaline dimaleate] were evaluated on 5-HT synthesis rates using the alpha
      [(14) C]methyl-l-tryptophan (alpha-MTrp) autoradiographic method. In the acute
      treatment study, TFMPP (10 mg/kg) and CGS12066B (5 mg/kg) were injected
      intraperitoneally 30 min before an alpha-MTrp injection. In an acute study TFMPP
      reduced overall brain 5-HT synthesis, in the dorsal and median raphe, and in
      almost all of their projection areas, with the exception of the parietal, sensory
      motor, and frontal cortices, the accumbens nucleus, and the caudate. Acute
      CGS12066B treatment did not have overall significant effect, but the rates did
      decrease in the cell body areas of 5-HT neurons. In a 7-day treatment with TFMPP
      (10 mg/kg/day) or CGS12066B (5 mg/kg/day), the 5-HT synthesis rates (24 h after
      last dose) decrease, with both compounds, in almost all of the nerve terminal
      structures. TFMPP reduced the synthesis in the dorsal and median raphe, while
      CGS12066B reduced it only in the dorsal raphe. This data suggests that after a 7
      day treatment with TFMPP and CGS12066B, the rate of 5-HT synthesis in the dorsal
      raphe is restored and is reduced in many projection areas. The observed effects
      in the 7-day treatment could also be related to actions through the postsynaptic
      5-HT(1B) sites and/or other 5-HT receptors since this compounds have limited
      selectivity.

PMID- 11948243
TI  - Expression of human beta-secretase in the mouse brain increases the steady-state
      level of beta-amyloid.
AB  - beta-Site APP-cleaving enzyme (BACE) initiates the processing of the amyloid
      precursor protein (APP) leading to the generation of beta-amyloid, the main
      component of Alzheimer's disease senile plaques. BACE (Asp2, memapsin 2) is a
      type I transmembrane aspartyl protease and is responsible for the beta-secretase
      cleavage of APP producing different endoproteolytic fragments referred to as the
      carboxy-terminal C99, C89 and the soluble ectodomain sAPPbeta. Here we describe
      two transgenic mouse lines expressing human BACE in the brain. Overexpression of
      BACE augments the amyloidogenic processing of APP as demonstrated by decreased
      levels of full-length APP and increased levels of C99 and C89 in vivo. In mice
      expressing huBACE in addition to human APP wild-type or carrying the Swedish
      mutation, the induction of APP processing characterized by elevated C99, C89 and
      sAPPbeta, results in increased brain levels of beta-amyloid peptides Abeta40 and
      Abeta42 at steady-state.

PMID- 11948244
TI  - Effects of estrogen treatment on glutamate uptake in cultured human astrocytes
      derived from cortex of Alzheimer's disease patients.
AB  - Estrogen is thought to play a protective role against neurodegeneration through a
      variety of mechanisms including the activation of growth factors, the control of
      synaptic plasticity, and the reduction of response to various insults, such as
      iron and glutamate. Increasing evidence indicates an increased level of
      extracellular glutamate and a down-regulation of glutamate transporters in
      Alzheimer's disease (AD). In this study, we show that glutamate uptake in
      astrocytes derived from Alzheimer's patients is significantly lower than that
      from non-demented controls. Estrogen treatment increases glutamate uptake in a
      dose-dependent pattern. Two glutamate transporters, GLT-1 and GLAST, are
      expressed in the astrocytes. Up-regulation of the glutamate transporters is
      induced by estrogen treatment in AD astrocytes only. Our data suggest that the
      action of estrogen on glutamate uptake by astrocytes might contribute to its
      potential neuroprotective role in AD.

PMID- 11948246
TI  - The production of macrophage inflammatory protein-2 induced by soluble
      intercellular adhesion molecule-1 in mouse astrocytes is mediated by src tyrosine
      kinases and p42/44 mitogen-activated protein kinase.
AB  - Severe traumatic brain injury stimulates the release of soluble intercellular
      adhesion molecule-1 (sICAM-1) into CSF. Studies in cultured mouse astrocytes
      suggest that sICAM-1 induces the production of macrophage inflammatory protein-2
      (MIP-2). In the present study, we investigated the underlying mechanisms for MIP
      2 induction. sICAM-1 induced MIP-2 in astrocytes lacking membrane-bound ICAM-1,
      indicating that its action is due to heterophilic binding to an undescribed
      receptor rather than homophilic binding to surface ICAM-1. Signal transduction
      may be mediated by src tyrosine kinases, as the src tyrosine kinase inhibitors
      herbimycin A and PP2 abolished MIP-2 induction by sICAM-1. Phosphorylation of
      p42/44 mitogen-activated protein kinase (MAPK), but not of p38 MAPK, occurred
      further downstream, as evidenced by western blot analysis combined with the use
      of herbimycin A and specific MAPK inhibitors. By contrast, induction of MIP-2 by
      tumour necrosis factor-alpha (TNF-alpha) involved both p42/44 MAPK and p38 MAPK.
      Following stimulation with either sICAM-1 or TNF-alpha, astrocyte supernatants
      promoted chemotaxis of human neutrophils and incubation of these supernatants
      with anti-MIP-2 antibodies more efficiently suppressed the migration induced by
      sICAM-1 than by TNF-alpha. These results show that sICAM-1 induces the production
      of biologically active MIP-2 in astrocytes by heterophilic binding to an
      undefined receptor and activation of src tyrosine kinases and p42/44 MAPK.

PMID- 11948245
TI  - Subunit specificity and interaction domain between GABA(A) receptor-associated
      protein (GABARAP) and GABA(A) receptors.
AB  - GABARAP (GABA(A) receptor-associated protein) interacts with both microtubules
      and GABA(A) receptors in vitro and in vivo and is capable of modulating receptor
      channel kinetics. In this study, we use the intracellular loop of 15 GABA(A)
      receptor subunits to show that the interaction between GABARAP and GABA(A)
      receptor is specific for the gamma subunits. Pharmacological characterization of
      proteins purified by GABARAP affinity column indicates that native GABA(A)
      receptors interact with GABARAP. Quantitative yeast two-hybrid assays were used
      to identify the interaction domain in the gamma2 subunit for GABARAP binding, and
      to identify the interaction domain in GABARAP for GABA(A) receptor binding. A
      peptide corresponding to the GABARAP interaction domain in the gamma2 subunit was
      used to inhibit the interaction between GABARAP and the gamma2 subunit. In
      addition, the ability of GABARAP to promote cluster formation of recombinant
      receptors expressed in QT-6 fibroblasts was inhibited by a membrane-permeable
      form of this peptide in a time-dependent manner. The establishment of a model for
      GABARAP-induced clustering of GABA(A) receptors in living cells and the
      identification of subunit specificity and interaction domains in the interaction
      between GABARAP and GABA(A) receptors is a step in dissecting the function of
      GABARAP in GABA(A) receptor clustering and/or targeting.

PMID- 11948248
TI  - A homeostatic mechanism counteracting K(+) -evoked choline release in adult
      brain.
AB  - Choline (Ch) is an essential nutrient as the biosynthetic precursor of
      acetylcholine (ACh) and phospholipids. Under resting conditions, the
      intracellular accumulation of Ch (above 10-fold), which is positively charged, is
      governed by the membrane potential and follows the Nernst equation. Accordingly,
      in synaptosomes from adult rats during depolarization, we observed a linear
      relationship between release of free cytoplasmic Ch and KCl concentration (2.7
      120 mm). The K(+) -evoked Ch release was Ca(2+) -independent and did not
      originate from ACh or phospholipid hydrolysis. In superfused brain slices of
      adult rats, however, a K(+) -induced Ch efflux was absent. Also, under in vivo
      conditions, 30-60 mm KCl failed to increase the extracellular Ch level as shown
      by microdialysis in adult rat hippocampus. On the contrary, in brain slices from
      1-week-old rats, high K(+) as well as 4-aminopyridine evoked a marked Ch efflux
      in a concentration-dependent fashion. This phenomenon faded within 1 week.
      Hemicholinium-3 (HC-3, 1 and 10 microm), a blocker of cellular choline uptake,
      caused a marked efflux of choline from adult rat slices but no or significantly
      less release from immature slices. We conclude that depolarization of synaptic
      endings causes a Ca(2+) -independent release of free cytoplasmic Ch into the
      extracellular space. In adult rat brain, this elevation of Ch is counteracted by
      a homeostatic mechanism such as uptake into brain cells.

PMID- 11948247
TI  - Bidirectional changes in synapsin I phosphorylation at MAP kinase-dependent sites
      by acute neuronal excitation in vivo.
AB  - Synapsin I is a synaptic vesicle-associated protein which is phosphorylated at
      multiple sites by various kinases. It has been proposed to play a role in the
      regulation of neurotransmitter release and the organization of cytoskeletal
      architecture in the presynaptic terminal. To better understand the physiological
      regulation of its phosphorylation in vivo, we induced acute, reversible neuronal
      excitation by electroconvulsive treatment (ECT) in rats, and studied its effects
      on synapsin I phosphorylation at sites 3, 4/5 and 6 by immunoblot analyses of
      homogenates from hippocampus and parietal cortex using phospho-site-specific
      antibodies. A decrease in phosphorylation at all sites was observed soon after
      the electrical stimulation, followed by a large increase in phosphorylation at
      site 4/5 peaking at 5 min and a moderate increase in phosphorylation at site 6
      peaking at 20 min. Systemic injection of SL327, a mitogen-activated protein
      kinase (MAPK) kinase inhibitor, prior to ECT, suppressed the increase in phospho
      site 4/5 level, as well as that in MAPK activity, but not that in phospho-site 6
      level. Thus, phosphorylation at site 4/5 of synapsin I has been shown to be
      regulated by MAPK in vivo.

PMID- 11948249
TI  - Effect of prenatal and postnatal ethanol exposure on the developmental profile of
      mRNAs encoding NMDA receptor subunits in rat hippocampus.
AB  - It has been proposed that assembly of the final NMDA receptor complex may be
      modified by prenatal ethanol exposure, resulting in long-term alterations of NMDA
      receptor pharmacology. We investigated the effect of prenatal and postnatal
      ethanol exposure on the developmental profile of mRNAs encoding NMDA receptor
      subunits in rat hippocampus. Female Sprague-Dawley rats were chronically
      intoxicated for 4 weeks with a 10% (v/v) ethanol solution administered throughout
      pregnancy and lactation. Hippocampus and cerebellum were isolated from pups
      (postnatal days 1-28) of the ethanol-exposed and ad libitum groups. Our results,
      using a semiquantitative RT-PCR technique, showed a selective effect of ethanol
      exposure on the various NMDA receptor subunits. Ethanol exposure significantly
      increased the levels of NR1(1XX), NR1(X11) and NR2(D) mRNAs on postnatal days 7
      and 14 and decreased the level of NR2(C) on postnatal day 1. Immunoblot analyses
      demonstrated that NR2(D) protein levels were increased on postnatal day 7 after
      ethanol exposure. However, the developmental profile of mRNAs encoding for NR2(A
      B), NR3(L/S), GBP and Gly/TCP-BP subunits were not affected. Moreover, no
      significant effects of ethanol exposure were observed on the developmental
      transition from expression of NR1(0XX) to NR(1XX) splice variants occurring in
      the cerebellum on postnatal day 19. Unexpectedly, [(3) H]MK-801 binding
      experiments showed that ethanol exposure increased the B (max) values of high
      affinity sites on postnatal days 14 and 28, with no change of K (d) values. These
      findings indicate that prenatal and/or postnatal ethanol exposure alters the
      hippocampal levels of mRNAs encoding for certain subunits and the density of high
      affinity [(3) H]MK-801 binding sites. As these subunits have been shown to
      modulate the functional properties of NMDA receptors, these results suggest that
      this altered expression could be involved in the neurodevelopmental disorders
      associated with fetal ethanol exposure.

PMID- 11948250
TI  - Ca(2+) -independent vesicular catecholamine release in PC12 cells by nanomolar
      concentrations of Pb(2+).
AB  - Effects of Pb(2+) on vesicular catecholamine release in intact and ionomycin
      permeabilized PC12 cells were investigated using carbon fibre microelectrode
      amperometry. Changes in intracellular Pb(2+) and Ca(2+) were measured from indo-1
      fluorescence by confocal laser scanning microscopy. Depolarization of intact
      cells and superfusion of permeabilized cells with saline containing > or = 100
      microm Ca(2+) rapidly evokes quantal catecholamine release. Superfusion with up
      to 10 microm Pb(2+) -containing saline evokes release of similar catecholamine
      quanta after a concentration-dependent delay. Thresholds to induce exocytosis
      within 30 min of exposure are between 1 and 10 microm Pb(2+) in intact cells and
      between 10 and 30 nm Pb(2+) in permeabilized cells. Additional inhibition of
      exocytosis occurs in permeabilized cells exposed to 10 microm Pb(2+). Using
      membrane-impermeable and -permeable chelators it is demonstrated that
      intracellular Ca(2+) is not required for Pb(2+) -induced exocytosis. In indo- 1
      loaded cells Pb(2+) reduces the fluorescence intensity after a concentration
      dependent delay, whereas the fluorescence ratio, indicating intracellular Ca(2+)
      concentration, remains unchanged. The delay to detect an increase in free
      intracellular Pb(2+) (> or = 30 nm) is much longer than the delay to Pb(2+) 
      induced exocytosis, indicating that cytoplasmic components buffer Pb(2+) with
      high affinity. It is concluded that Pb(2+) acts as a high-affinity substitute for
      Ca(2+) to trigger essential steps leading to vesicular catecholamine release,
      which occurs when only approximately 20% of the intracellular high-affinity
      binding capacity ( approximately 2 attomol/cell) is saturated with Pb(2+).

PMID- 11948251
TI  - Effect of precipitated morphine withdrawal on post-translational processing of
      prothyrotropin releasing hormone (proTRH) in the ventrolateral column of the
      midbrain periaqueductal gray.
AB  - We have demonstrated that during opiate withdrawal, preprothyrotropin releasing
      hormone (preproTRH) mRNA is increased in neurons of the midbrain periaqueductal
      gray matter (PAG) while the concentration of TRH remained unaltered, suggesting
      that the processing of proTRH may be different in this region of the brain. The
      aim of the present study was to determine which of the proTRH-derived peptides
      are affected by opiate withdrawal in the PAG. These changes were compared to
      other TRH-containing areas such as the hypothalamic paraventricular nucleus
      (PVN), median eminence (ME) and the lateral hypothalamus (LH). Control and
      morphine-treated rats 24 h following naltrexone-precipitated withdrawal were
      decapitated and the brain microdissected. Pooled samples from each animal group
      were acid extracted, and peptides were electrophoretically separated then
      analyzed by specific radioimmunoassay. Opiate withdrawal caused a significant
      change in the level of some post-translational processing products derived from
      the TRH precursor. In the PAG, opiate withdrawal resulted in an accumulation of
      the intervening preproTRH(83-106) peptide from the N-terminal side of the
      prohormone, while the levels of the C-terminal preproTRH(208-285) peptide were
      reduced, with no change in preproTRH(25-50) or TRH, itself, as compared to
      control animals. Immunohistochemical analysis also showed significant increases
      in cellular preproTRH(83-106) peptide immunolabeling in the PAG. Opiate
      withdrawal in the lateral hypothalamus, unlike from the PAG, was accompanied by
      an increase in the concentration of TRH. In addition, western blot analysis
      showed that during opiate withdrawal, the mature form of the prohormone
      convertase 2 (PC2) increased only in PAG as compared with their respective
      controls. Thus, these results demonstrate a region-specific regulation of TRH
      prohormone processing in the brain, which may engage PC2, further suggesting a
      role for specific proTRH-derived peptides in the manifestations of opiate
      withdrawal.

PMID- 11948252
TI  - Characterization of the cocaine- and amphetamine-regulated transcript (CART)
      peptide gene promoter and its activation by a cyclic AMP-dependent signaling
      pathway in GH3 cells.
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptides are regulated
      neuropeptides that play a role in a variety of physiological processes. CART mRNA
      is also highly regulated as its levels change in response to psychostimulant
      drugs and leptin. To understand the mechanisms involved in regulating CART mRNA
      levels, the mouse CART 5'-flanking regulatory region was studied. The sequence of
      3.4 kb of the mouse CART 5'-flanking region revealed a proximal promoter that
      contains a cluster of transcription factor binding sites, including an
      overlapping STAT/CRE/AP1 site. In addition, the 5'-most 320 bp of the CART
      promoter shares 83% nucleotide identity between mouse and human. Three luciferase
      expressing constructs containing varying amounts of CART 5' upstream sequence
      were generated and tested for promoter activity. Transient transfection of GH3
      cells with constructs containing 641 and 3451 bp of upstream sequence displayed
      strong promoter activity, producing 29-fold and 51-fold stimulation,
      respectively, while, a construct containing 102 bp of upstream sequence displayed
      a 5.4-fold increase in activity. A construct containing the composite
      STAT/CRE/AP1 site was responsive to cyclic AMP induction by forskolin in GH3
      cells. Forskolin treatment also resulted in a 4.5-fold increase in CART mRNA
      levels after 6 h and the addition of H89, an inhibitor of protein kinase A,
      reduced the levels by 50%. These studies indicate that the CART proximal promoter
      lies within the 5'-most 641 bp and that in GH3 cells the CART gene is regulated
      via a cyclic AMP-dependent pathway.

PMID- 11948253
TI  - Local and systemic increase in lipid peroxidation after moderate experimental
      traumatic brain injury.
AB  - Traumatic brain injury is a common event associated with neurological
      dysfunction. Oxidative damage, may contribute to some of these pathologic
      changes. We used a specific and sensitive marker of lipid peroxidation, the
      isoprostane 8,12-iso-iPF(2alpha) -VI, to investigate whether local and also
      systemic lipid peroxidation were induced following lateral fluid percussion (FP)
      brain injury in the rat. Animals were anesthetized and subjected to lateral FP
      brain injury of moderate severity, or to sham injury as controls. Urine was
      collected before anesthesia (baseline), 6 and 24 h after injury. Blood was
      collected at baseline, 1, 6 and 24 h after injury. Animals were killed 24 h after
      surgery and their brains removed for biochemical analysis. No significant
      difference was observed at baseline (preinjury) for urine and plasma 8,12-iso
      iPF(2alpha) -VI levels between injured and sham-operated animals. By contrast,
      plasma and urinary levels increased significantly already at 1 and further
      increased 24 h following brain injury, when compared to sham-operated animals.
      Finally, compared with sham, injured animals had a significant increase in brain
      8,12-iso-iPF(2alpha) -VI levels. These results demonstrate that moderate brain
      injury induces widespread brain lipid peroxidation, which is accompanied by a
      similar increase in urine and plasma. Peripheral measurement of 8,12-iso
      iPF(2alpha) -VI levels after brain injury may be a reliable marker of brain
      oxidative damage.

PMID- 11948254
TI  - Evidence for a gamma-hydroxybutyrate (GHB) uptake by rat brain synaptic vesicles.
AB  - gamma-Hydroxybutyrate (GHB) is an endogenous metabolite of mammalian brain which
      is derived from GABA. Much evidence favours its role as an endogenous
      neuromodulator, synthesized, stored and released at particular synapses
      expressing specific receptors. One key step for GHB involvement in
      neurotransmission is its uptake by a specific population of synaptic vesicles. We
      demonstrate that this specific uptake exists in a crude synaptic vesicle pool
      obtained from rat brain. The kinetic parameters and the pharmacology of this
      transport are in favour of an active vesicular uptake system for GHB via the
      vesicular inhibitory amino acid transporter. This result supports the idea that
      GABA and GHB accumulate together and are coliberated in some GABAergic synapses
      of the rat brain, where GHB acts as a modulatory factor for the activity of these
      synapses following stimulation of specific receptors.

PMID- 11948256
TI  - PK 11195 attenuates kainic acid-induced seizures and alterations in peripheral
      type benzodiazepine receptor (PBR) protein components in the rat brain.
AB  - Peripheral-type benzodiazepine receptors (PBR) are located in glial cells in the
      brain and in peripheral tissues. Mitochondria form the primary location for PBR.
      Functional PBR appear to require at least three components: an isoquinoline
      binding protein, a voltage-dependent anion channel, and an adenine nucleotide
      carrier. In the present study, rats received intraperitoneal kainic acid
      injections, which are known to cause seizures, neurodegeneration, hyperactivity,
      gliosis, and a fivefold increase in PBR ligand binding density in the
      hippocampus. In the forebrain of control rats, hippocampal voltage-dependent
      anion channel and adenine nucleotide carrier abundance was relatively low, while
      isoquinoline binding protein abundance did not differ between hippocampus and the
      rest of the forebrain. One week after kainic acid injection, isoquinoline binding
      protein abundance was increased more than 20-fold in the hippocampal
      mitochondrial fraction. No significant changes were detected regarding
      hippocampal voltage-dependent anion channel and adenine nucleotide carrier
      abundance. Pre-treatment with the isoquinoline PK11195, a specific PBR ligand,
      attenuated the occurrence of seizures, hyperactivity, and increases in
      isoquinoline binding protein levels in the hippocampus, which usually follow
      kainic acid application. These data suggest that isoquinoline binding protein may
      be involved in these effects of kainic acid injections.

PMID- 11948255
TI  - A direct role of the homeodomain proteins Phox2a/2b in noradrenaline
      neurotransmitter identity determination.
AB  - Development of noraderenergic (NA) neurons in the vertebrate brain is dependent
      on the homeodomain proteins Phox2a and 2b. Here, we show that Phox2a directly
      controls the NA identity by activating NA-synthesizing dopamine beta-hydroxylase
      (DBH ) gene. Single point mutations in the homeodomain of Phox2a resulted in a
      failure to transactivate the DBH promoter in vitro and resulted in the loss of NA
      neurons in vivo. In addition, injection of Phox2a-specific antisense
      oligonucleotide induced the loss of NA neurons in developing zebrafish. Phox2a
      and 2b activate the DBH promoter and bind to three domains (PBD1-3). PBD1 is
      composed of two overlapping sites with which monomers of Phox2a can interact. In
      contrast, PBD2 and 3 interact with the dimeric form of Phox2a. Mutations in three
      or four, but not one or two, of the binding sites completely abolished activation
      of the DBH promoter by Phox2a or 2b, while the conversion of PBD3 to a consensus
      motif (ATTA) improved the DBH promoter activity by > 10-fold. Taken together,
      these findings establish that Phox2a and 2b control the development of NA neurons
      in part by directly transactivating DBH transcription through interactions with
      four binding sites clustered in the proximal promoter.

PMID- 11948260
TI  - Clinical applications of (18)F-FDG in oncology.
AB  - PET has emerged as a powerful diagnostic tool for the evaluation of cancer
      patients. Currently, most of these studies are performed with the glucose analog
      (18)F-FDG, which has been shown to accumulate avidly in most tumors. (18)F-FDG
      PET is now routinely used in the diagnosis, staging, and posttherapy evaluation
      of oncologic patients. After reading this paper, the reader should understand the
      physiologic basis of using (18)F-FDG in patients with different tumors, describe
      the role of this radiopharmaceutical in the management of oncologic patients, and
      identify those malignancies for which (18)F-FDG has proved to be effective in
      diagnosis and follow-up.

PMID- 11948257
TI  - Hypoxia induces mitochondrial DNA damage and stimulates expression of a DNA
      repair enzyme, the Escherichia coli MutY DNA glycosylase homolog (MYH), in vivo,
      in the rat brain.
AB  - Hypoxia-associated, acutely reduced blood oxygenation can compromise energy
      metabolism, alter oxidant/antioxidant balance and damage cellular components,
      including DNA. We show in vivo, in the rat brain that respiratory hypoxia leads
      to formation of the oxidative DNA lesion, 8-hydroxy-2'-deoxyguanosine (oh8dG), a
      biomarker for oxidative DNA damage and to increased expression of a DNA repair
      enzyme involved in protection of the genome from the mutagenic consequences of
      oh8dG. The enzyme is a homolog of the Escherichia coli MutY DNA glycosylase
      (MYH), which excises adenine residues misincorporated opposite the oxidized base,
      oh8dG. We have cloned a full-length rat MYH (rMYH) cDNA, which encodes 516 amino
      acids, and by in situ hybridization analysis obtained expression patterns of rMYH
      mRNA in hippocampal, cortical and cerebellar regions. Ensuing hypoxia,
      mitochondrial DNA damage was induced and rMYH expression strongly elevated. This
      is the first evidence for a regulated expression of a DNA repair enzyme in the
      context of respiratory hypoxia. Our findings support the premise that oxidative
      DNA damage is repaired in neurons and the possibility that the hypoxia-induced
      expression of a DNA repair enzyme in the brain represents an adaptive mechanism
      for protection of neuronal DNA from injurious consequences of disrupted energy
      metabolism and oxidant/antioxidant homeostasis.

PMID- 11948262
TI  - Contamination problem with sentinel node localization procedure: a case study.
AB  - Lymphoscintigraphy for sentinel node (SN) localization was performed on a 60-y
      old man with a melanoma on his back. Skin contamination occurred as a result of
      the radiopharmaceutical dose administration. Skin contamination could result in a
      misinterpretation of the SN location. Careful observation of the procedure
      avoided a misinterpretation with this study.

PMID- 11948261
TI  - Whole-body lymphoscintigraphy using transmission scans.
AB  - OBJECTIVE: Our objective was to show the advantages of performing whole-body
      lymphoscintigraphy using transmission sources. This technique should decrease
      scanning time, help locate the sentinel lymph node, and decrease radiation
      exposure to the technologist. METHODS: Twenty patients with proven melanoma
      received 18.5 MBq (0.5 mCi) filtered (0.22 microm) (99m)Tc-sulfur colloid in a
      0.2-mL volume, administered as multiple intradermal or subcutaneous injections
      around the known melanoma lesion or scar. All 20 patients underwent serial static
      imaging immediately after the injection, along with whole-body scanning after the
      static imaging. The static emission images were acquired for 5 min and the
      transmission images for 1 min using a 256 x 256 matrix. The whole-body
      transmission scans were acquired after the whole-body emission scans. The
      transmission scans were obtained with the same parameters as the emission scans,
      with the addition of placement of a (57)Co sheet source on one of the detectors
      of the large-field-of-view dual-head camera. The planar static axial images
      (transmission, emission) were compared with the whole-body images (transmission,
      emission) to determine whether the same number of lymph nodes was visualized with
      each technique. Posterior outlines were obtained through computer manipulation of
      anterior transmission images. RESULTS: In all 20 patients, the number of lymph
      nodes seen on the static images was the same as that seen on the whole-body
      emission and transmission images. The whole-body emission and transmission
      scanning time was an average of 30 min less than the time required to acquire the
      serial static images. CONCLUSION: The anatomic location of the sentinel lymph
      node is seen more easily on whole-body images, both anterior transmission and
      posterior transmission, than on planar static images. Whole-body emission and
      transmission imaging decreased scanning time and thus improved patient comfort
      and throughput. Technologists received less radiation exposure when handling the
      (57)Co source only twice during whole-body imaging, as opposed to several times
      during static imaging.

PMID- 11948263
TI  - Adverse reactions to dipyridamole in patients undergoing stress/rest cardiac
      perfusion testing.
AB  - OBJECTIVE: A reaction scale was used to assess noncardiac adverse reactions
      exhibited by nuclear medicine outpatients receiving intravenous dipyridamole for
      pharmacological stress testing. METHODS: The study included 933 patients referred
      to 2 cardiac outpatient centers for assessment. All patients evaluated in this
      study were unable to perform treadmill stress testing and underwent
      pharmacological intravenous dipyridamole stress testing. Dual-isotope (201)Tl
      rest/(99m)Tc-sestamibi stress imaging was performed. An analysis of adverse
      reactions exhibited by patients given dipyridamole was tabulated. RESULTS: Of the
      933 patients, 520 (55.7%) demonstrated no adverse reaction to intravenous
      dipyridamole; 413 patients (44.3%) had adverse reactions of some type. Many of
      these patients had multiple types of reactions, and a total of 604 reactions were
      recorded. The most prevalent adverse reaction was headache (224 reactions;
      37.1%), followed by chest pain (73 reactions; 12.1%), and nausea (67 reactions;
      11.1%). A sex comparison revealed 271 of 454 male patients (59.7%) and 249 of 479
      female patients (52%) demonstrated no adverse reaction to intravenous
      dipyridamole. An evaluation of the most prevalent adverse reaction (headache)
      demonstrated a significant difference between males (37.9%) and females (62.1%).
      CONCLUSION: An adverse reaction scale characterizing common noncardiac side
      effects of dipyridamole in nuclear medicine cardiac patients demonstrated the
      most prevalent adverse reaction was headache. Analysis by sex revealed that
      significantly more females than males complained of headaches.

PMID- 11948266
TI  - NMTCB "state of the union".

PMID- 11948267
TI  - Increase in radiologic science students, survey shows.

PMID- 11948264
TI  - Measuring and minimizing the radiation dose to nuclear medicine technologists.
AB  - OBJECTIVE: Nuclear medicine technologists rely on a single dosimeter to measure
      their work-related dose. Estimates of whole-body effective dose are based on the
      assumptions that the radiation is incident from the front and in a uniform beam.
      We sought to investigate these assumptions and also to quantify doses associated
      with different activities. METHODS: A single technologist wore 3 electronic
      dosimeters for 3 mo, at the front waist, the back waist, and the front collar.
      The technologist also recorded her activities throughout the day. RESULTS: We
      found that the assumption of an anterior beam held about two thirds of the time,
      breaking down only when the technologist was receiving lower doses. Overall, the
      average whole-body dose was estimated correctly by assuming an anterior beam. We
      also found that irradiation was uniform (i.e., waist and collar badges gave
      equivalent readings) except when the technologist was performing injections.
      Then, the collar readings were 1.7 times the waist readings. Finally, average
      doses were measured for different types of activities. Performing injections
      registered a dose rate of approximately 2 microSv/h. Doses received while
      scanning ranged from 0.2 to 2 microSv/h. The average dose for a scan depended not
      only on the administered activity and isotope but also on the amount of patient
      contact required. Even for high activities, such as patients who had already
      received therapy, the dose to the technologist was low for patients requiring
      little assistance. CONCLUSION: The assumption of anterior irradiation correctly
      estimates whole-body effective dose. The assumption of a uniform beam is good
      except when injections are being performed, when the upper torso receives a much
      higher dose than the waist. Overall, doses to the technologist were found to be
      5.4 microSv/d for scanning and 12 microSv/d for injections. These correspond to
      1.4 mSv/y and 3.2 mSv/y, respectively, which are comparable to naturally
      occurring radiation levels and are much lower than regulatory limits. However, if
      the dose to a particular technologist needs to be minimized (e.g., for a pregnant
      worker), the most effective strategy is for the technologist to be assigned
      patients requiring little contact or assistance and, in particular, to avoid
      administering injections.

PMID- 11948268
TI  - Fish -- food to calm the heart.

PMID- 11948269
TI  - Male circumcision, penile human papillomavirus infection, and cervical cancer in
      female partners.
AB  - BACKGROUND: It is uncertain whether male circumcision reduces the risks of penile
      human papillomavirus (HPV) infection in the man and of cervical cancer in his
      female partner. METHODS: We pooled data on 1913 couples enrolled in one of seven
      case-control studies of cervical carcinoma in situ and cervical cancer in five
      countries. Circumcision status was self-reported, and the accuracy of the data
      was confirmed by physical examination at three study sites. The presence or
      absence of penile HPV DNA was assessed by a polymerase-chain-reaction assay in
      1520 men and yielded a valid result in the case of 1139 men (74.9 percent).
      RESULTS: Penile HPV was detected in 166 of the 847 uncircumcised men (19.6
      percent) and in 16 of the 292 circumcised men (5.5 percent). After adjustment for
      age at first intercourse, lifetime number of sexual partners, and other potential
      confounders, circumcised men were less likely than uncircumcised men to have HPV
      infection (odds ratio, 0.37; 95 percent confidence interval, 0.16 to 0.85).
      Monogamous women whose male partners had six or more sexual partners and were
      circumcised had a lower risk of cervical cancer than women whose partners were
      uncircumcised (adjusted odds ratio, 0.42; 95 percent confidence interval, 0.23 to
      0.79). Results were similar in the subgroup of men in whom circumcision was
      confirmed by medical examination. CONCLUSIONS: Male circumcision is associated
      with a reduced risk of penile HPV infection and, in the case of men with a
      history of multiple sexual partners, a reduced risk of cervical cancer in their
      current female partners.

PMID- 11948270
TI  - Blood levels of long-chain n-3 fatty acids and the risk of sudden death.
AB  - BACKGROUND: Experimental data suggest that long-chain n-3 polyunsaturated fatty
      acids found in fish have antiarrhythmic properties, and a randomized trial
      suggested that dietary supplements of n-3 fatty acids may reduce the risk of
      sudden death among survivors of myocardial infarction. Whether long-chain n-3
      fatty acids are also associated with the risk of sudden death in those without a
      history of cardiovascular disease is unknown. METHODS: We conducted a
      prospective, nested case-control analysis among apparently healthy men who were
      followed for up to 17 years in the Physicians' Health Study. The fatty-acid
      composition of previously collected blood was analyzed by gas-liquid
      chromatography for 94 men in whom sudden death occurred as the first
      manifestation of cardiovascular disease and for 184 controls matched with them
      for age and smoking status. RESULTS: Base-line blood levels of long-chain n-3
      fatty acids were inversely related to the risk of sudden death both before
      adjustment for potential confounders (P for trend = 0.004) and after such
      adjustment (P for trend = 0.007). As compared with men whose blood levels of long
      chain n-3 fatty acids were in the lowest quartile, the relative risk of sudden
      death was significantly lower among men with levels in the third quartile
      (adjusted relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.87) and
      the fourth quartile (adjusted relative risk, 0.19; 95 percent confidence
      interval, 0.05 to 0.71). CONCLUSIONS: The n-3 fatty acids found in fish are
      strongly associated with a reduced risk of sudden death among men without
      evidence of prior cardiovascular disease.

PMID- 11948271
TI  - A controlled trial of valganciclovir as induction therapy for cytomegalovirus
      retinitis.
AB  - BACKGROUND: Valganciclovir is an orally administered prodrug that is rapidly
      hydrolyzed to ganciclovir. We compared the effects of oral valganciclovir with
      those of intravenous ganciclovir as induction therapy for newly diagnosed
      cytomegalovirus retinitis in 160 patients with the acquired immunodeficiency
      syndrome (AIDS). METHODS: The primary end point was photographically determined
      progression of cytomegalovirus retinitis within four weeks after the initiation
      of treatment. Secondary end points included the achievement of a prospectively
      defined satisfactory response to induction therapy and the time to progression of
      cytomegalovirus retinitis. After four weeks, all patients received valganciclovir
      as maintenance therapy. RESULTS: Eighty patients were randomly assigned to each
      treatment group. Of the patients who could be evaluated, 7 of 70 assigned to
      intravenous ganciclovir (10.0 percent) and 7 of 71 assigned to oral
      valganciclovir (9.9 percent) had progression of cytomegalovirus retinitis during
      the first four weeks (difference in proportions, 0.1 percentage point; 95 percent
      confidence interval, -9.7 to 10.0). Forty-seven of 61 patients (77.0 percent)
      assigned to intravenous ganciclovir and 46 of 64 (71.9 percent) assigned to
      valganciclovir had a satisfactory response to induction therapy (difference in
      proportions, 5.2 percentage points; 95 percent confidence interval, -20.4 to
      10.1). The median times to progression of retinitis were 125 days in the group
      assigned to intravenous ganciclovir and 160 days in the group assigned to oral
      valganciclovir. The mean values for the area under the curve for the ganciclovir
      dosage interval were similar at both induction doses and maintenance doses. The
      frequency and severity of adverse events were similar in the two treatment
      groups. CONCLUSIONS: Orally administered valganciclovir appears to be as
      effective as intravenous ganciclovir for induction treatment and is convenient
      and effective for the long-term management of cytomegalovirus retinitis in
      patients with AIDS.

PMID- 11948272
TI  - Images in clinical medicine. Herpes zoster ophthalmicus followed by contralateral
      hemiparesis.

PMID- 11948273
TI  - Hospital volume and surgical mortality in the United States.
AB  - BACKGROUND: Although numerous studies suggest that there is an inverse relation
      between hospital volume of surgical procedures and surgical mortality, the
      relative importance of hospital volume in various surgical procedures is
      disputed. METHODS: Using information from the national Medicare claims data base
      and the Nationwide Inpatient Sample, we examined the mortality associated with
      six different types of cardiovascular procedures and eight types of major cancer
      resections between 1994 and 1999 (total number of procedures, 2.5 million).
      Regression techniques were used to describe relations between hospital volume
      (total number of procedures performed per year) and mortality (in-hospital or
      within 30 days), with adjustment for characteristics of the patients. RESULTS:
      Mortality decreased as volume increased for all 14 types of procedures, but the
      relative importance of volume varied markedly according to the type of procedure.
      Absolute differences in adjusted mortality rates between very-low-volume
      hospitals and very-high-volume hospitals ranged from over 12 percent (for
      pancreatic resection, 16.3 percent vs. 3.8 percent) to only 0.2 percent (for
      carotid endarterectomy, 1.7 percent vs. 1.5 percent). The absolute differences in
      adjusted mortality rates between very-low-volume hospitals and very-high-volume
      hospitals were greater than 5 percent for esophagectomy and pneumonectomy, 2 to 5
      percent for gastrectomy, cystectomy, repair of a nonruptured abdominal aneurysm,
      and replacement of an aortic or mitral valve, and less than 2 percent for
      coronary-artery bypass grafting, lower-extremity bypass, colectomy, lobectomy,
      and nephrectomy. CONCLUSIONS: In the absence of other information about the
      quality of surgery at the hospitals near them, Medicare patients undergoing
      selected cardiovascular or cancer procedures can significantly reduce their risk
      of operative death by selecting a high-volume hospital.

PMID- 11948275
TI  - Clinical practice. Nephropathy in patients with type 2 diabetes.

PMID- 11948274
TI  - Variations in morbidity after radical prostatectomy.
AB  - BACKGROUND: Recent studies of surgery for cancer have demonstrated variations in
      outcomes among hospitals and among surgeons. We sought to examine variations in
      morbidity after radical prostatectomy for prostate cancer. METHODS: We used the
      Surveillance, Epidemiology, and End Results-Medicare linked data base to evaluate
      health-related outcomes after radical prostatectomy. The rates of postoperative
      complications, late urinary complications (strictures or fistulas 31 to 365 days
      after the procedure), and long-term incontinence (more than 1 year after the
      procedure) were inferred from the Medicare claims records of 11,522 patients who
      underwent prostatectomy between 1992 and 1996. These rates were analyzed in
      relation to hospital volume and surgeon volume (the number of procedures
      performed at individual hospitals and by individual surgeons, respectively).
      RESULTS: Neither hospital volume nor surgeon volume was significantly associated
      with surgery-related death. Significant trends in the relation between volume and
      outcome were observed with respect to postoperative complications and late
      urinary complications. Postoperative morbidity was lower in very-high-volume
      hospitals than in low-volume hospitals (27 percent vs. 32 percent, P=0.03) and
      was also lower when the prostatectomy was performed by very-high-volume surgeons
      than when it was performed by low-volume surgeons (26 percent vs. 32 percent,
      P<0.001). The rates of late urinary complications followed a similar pattern.
      Results for long-term preservation of continence were less clear-cut. In a
      detailed analysis of the 159 surgeons who had a high or very high volume of
      procedures, wide surgeon-to-surgeon variations in these clinical outcomes were
      observed, and they were much greater than would be predicted on the basis of
      chance or observed variations in the case mix. CONCLUSIONS: In men undergoing
      prostatectomy, the rates of postoperative and late urinary complications are
      significantly reduced if the procedure is performed in a high-volume hospital and
      by a surgeon who performs a high number of such procedures.

PMID- 11948276
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 11-2002. A 27-year-old woman with two intracardiac masses and a
      history of endocrinopathy.

PMID- 11948277
TI  - Cervical cancer and the elusive male factor.

PMID- 11948278
TI  - Volume and outcome--it is time to move ahead.

PMID- 11948279
TI  - Luxury primary care--market innovation or threat to access?

PMID- 11948280
TI  - Warfarin or aspirin for recurrent ischemic stroke.

PMID- 11948281
TI  - Nonsteroidal drugs and Alzheimer's disease.

PMID- 11948282
TI  - Valsartan in chronic heart failure.

PMID- 11948283
TI  - Botulinum toxin for cricopharyngeal dysfunction in Parkinson's disease.

PMID- 11948284
TI  - Large errors in the dosing of medications for children.

PMID- 11948285
TI  - Microsatellite variation associated with prolactin expression and growth of salt
      challenged tilapia.
AB  - Biologists have long argued that runs of alternating purines and pyrimidines
      could form alternative DNA structures, which might regulate transcription. Here,
      we report that simple sequence repeat polymorphisms in the tilapia prolactin 1
      (prl 1) promoter are associated with differences in prl 1 gene expression and the
      growth response of salt-challenged fishes. Individuals homozygous for long
      microsatellite alleles express less prl 1 in fresh water but more prl 1 in half
      seawater than fishes with other genotypes. Our work provides the first in vivo
      evidence that differences in microsatellite length among individuals may indeed
      affect gene expression and that variance in expression has concomitant
      physiological consequences. These results suggest that dinucleotide
      microsatellites represent an under-appreciated source of genetic variation for
      regulatory evolution.

PMID- 11948286
TI  - Changes in urinary bladder cytokine mRNA and protein after cyclophosphamide
      induced cystitis.
AB  - Cyclophosphamide (CYP)-induced cystitis alters micturition function and produces
      reorganization of the micturition reflex. This reorganization may involve
      cytokine expression in the urinary bladder. These studies have determined
      candidate cytokines in the bladder that may contribute to the reorganization
      process. An RNase protection assay was used to measure changes in rat bladder
      cytokine mRNA [interferon-gamma (IFN)-gamma, interleukin-1alpha/beta (IL
      1alpha/beta), IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, and tumor necrosis factor
      alpha/beta (TNF-alpha/beta)] after acute (4 h), intermediate (48 h), or chronic
      (10 day) cystitis. The correlation between bladder cytokine mRNA and protein
      expression was also determined by immunoassay. Although at each time point after
      cystitis significant changes in bladder cytokine mRNA were observed, the
      magnitude differed (acute > intermediate > chronic). Acute cystitis demonstrated
      the most robust changes (P </= 0.005; IL-1beta, 330-fold increase; IL-2, 20-fold
      increase; IL-4, 8-fold increase; IL-6, 80-fold increase) in cytokine mRNA
      expression and TNF-alpha or TNF-beta mRNA were only increased (2-10-fold) after
      acute cystitis. More modest increases in cytokine mRNA expression were observed
      after 48-h or 10-day cystitis. Cytokine protein expression generally paralleled
      that of mRNA. Increased cytokine expression after CYP-induced cystitis, alone or
      in combination with other inflammatory mediators or growth factors, may
      contribute to altered lower urinary tract function after cystitis.

PMID- 11948287
TI  - Physiological genomics of Escherichia coli protein families.
AB  - The well-researched Escherichia coli genome offers the opportunity to explore the
      value of using protein families within a single organism to enrich functional
      annotation procedures and to study mechanisms of protein evolution. Having
      identified multimodular proteins resulting from gene fusion, and treated each
      module as a separate protein, nonoverlapping sequence-similar families in E. coli
      could be assembled. Of 3,902 proteins of length 100 residues or more, 2,415
      clustered into 609 protein families. The relatedness of function among members of
      each family was dissected in detail. Data on paralogous protein families provides
      valuable information in attributing putative function to unknown genes,
      supplementing existing function annotation. Enzymes, transporters, and regulators
      represent the three major types of proteins in E. coli. They are shown to have
      distinctive patterns in gene duplication and divergence and gene fusion,
      suggesting that details of protein evolution have been different for genes in
      these categories. Data for the complete list of paralogous protein families and
      updated functional annotation for E. coli K-12 are accessible in GenProtEC
      (http://genprotec.mbl.edu).

PMID- 11948288
TI  - Gene expression profiling of human aortic endothelial cells exposed to disturbed
      flow and steady laminar flow.
AB  - Subtraction cloning and cDNA arrays were used to compare steady-state mRNA levels
      in cultured human aortic endothelial cells (HAEC) exposed for up to 24 h to
      either high-shear (13 dyn/cm(2)) steady laminar flow (LF), an established
      representation of "atheroprotective" flow conditions, or low-shear (<1
      dyn/cm(2)), pulsatile, nonsteady, non-unidirectional flow (disturbed flow, DF)
      that simulates conditions in the atherosclerosis-prone areas of the arterial
      circulation. More than 100 genes not previously known to be flow regulated were
      identified. Analysis of selected genes by quantitative RT-PCR confirmed the
      results obtained from the microarrays. These data demonstrate that DF is not
      simply the absence of LF but in fact represents a distinct biomechanical stimulus
      that has a profound impact upon the gene expression profile of HAEC in culture.
      In line with previous studies, many of the changes in mRNA levels induced by LF
      are atheroprotective. In contrast, DF upregulated the mRNA levels of a plethora
      of proatherosclerotic genes including proinflammatory, proapoptotic, and
      procoagulant molecules. For some of the genes whose expression was altered by DF
      and LF, corresponding changes in EC function (proliferation and monocyte
      adhesion) could be demonstrated. Specifically, the sustained upregulation of VCAM
      1 and increased monocyte adhesion to EC exposed to DF was similar to that found
      in EC in vivo at atherosclerosis-prone regions, confirming the relevance of our
      model system for in vivo conditions. Distinct differences in the cellular
      response induced by TNFalpha and DF suggest that the effects of DF are not
      mediated entirely by the same signaling pathways that activate NF-kappaB. These
      studies demonstrate extensive and pathophysiologically relevant changes in
      sustained gene expression patterns in aortic EC exposed to DF compared with LF
      which are predicted to induce a proatherogenic EC phenotype.

PMID- 11948289
TI  - The hypertrophic heart rat: a new normotensive model of genetic cardiac and
      cardiomyocyte hypertrophy.
AB  - We describe a new line of rats with inherited cardiomyocyte and ventricular
      hypertrophy. From a second-generation cross of spontaneously hypertensive and
      Fischer 344 rats, we selected for low blood pressure and either high or low
      echocardiographic left ventricular (LV) mass over four generations to establish
      the hypertrophic heart rat (HHR) and normal heart rat (NHR) lines, respectively.
      After 13 generations of inbreeding, HHR had significantly greater (P < 0.0001) LV
      mass-to-body weight ratio (2.68 g/kg, SE 0.14) than NHR matched for age (1.94
      g/kg, SE 0.02) or body weight (2.13 g/kg, SE 0.03). The isolated cardiomyocytes
      of HHR were significantly (P < 0.0001) longer and wider (161 microm, SE 0.83;
      35.6 microm, SE 2.9) than NHR (132 microm, SE 1.2; 29.5 microm, SE 0.35).
      Telemetric 24-h recordings of mean arterial pressure revealed no significant
      differences between HHR and NHR. The HHR offers a new model of primary
      cardiomyocyte hypertrophy with normal blood pressure in which to examine
      genotypic causes and pathogenetic mechanisms of hypertrophy and its
      complications.

PMID- 11948291
TI  - Staging of gastric cancer: a study with spiral computed tomography,
      ultrasonography, laparoscopy, and laparoscopic ultrasonography.
AB  - In this study, we evaluated and compared the value of spiral computed tomography,
      transabdominal ultrasonography, laparoscopy, and laparoscopic ultrasonography in
      staging gastric cancer in 37 patients; there was a special interest in the
      additional information provided by laparoscopic ultrasonography. Although
      laparoscopy was unreliable or hindered by adhesions in 11% of the patients, the
      benefit of laparoscopy for staging was evident especially for the detection of
      peritoneal carcinomatosis that was missed by the other diagnostic modalities.
      Laparoscopic ultrasonography did not change the stage of the disease nor the
      decision whether to proceed with laparotomy for any of the patients. The decision
      whether to proceed with laparotomy was correctly predicted in 95% of the cases.

PMID- 11948292
TI  - Vascular complications in percutaneous transhepatic management of complicated
      hepatolithiasis with difficult intrahepatic biliary strictures: are they
      avoidable?
AB  - Little has been reported about hemobilia in the management of complicated
      residual or recurrent hepatolithiasis with intrahepatic biliary strictures by
      percutaneous stricture dilation and percutaneous transhepatic cholangioscopic
      lithotomy. To analyze retrospectively the incidence, possible factors, and
      management of hemobilia in such patients, a consecutive series of 177 patients
      was studied from 1983 to 2001: 90 patients in the early, 7.5-year period and 87
      patients in the later period, in which some procedures were modified. Minor
      hemobilia occurred during percutaneous puncture in 6 patients: 4 (4.4%) in the
      early period and 2 (2.3%) in the later period. Massive hemobilia developed in 14
      patients (15.5%) in only the early period, during stricture dilation,
      lithotripsy, or lithotomy. Immediate arteriography revealed arterial bleeding
      (7), extravasation (3), pseudoaneurysm (3), or an undetermined source (1).
      Transcatheter arterial intervention enabled successful hemostasis. Massive
      hemobilia is a potential serious complication of percutaneous stricture dilation
      and percutaneous transhepatic cholangioscopic lithotomy but is avoidable.

PMID- 11948290
TI  - Novel technique of aortic banding followed by gene transfer during hypertrophy
      and heart failure.
AB  - Aortic banding in the rat has become a popular method to induce left ventricular
      (LV) hypertrophy and heart failure. However, because of often extensive
      intrathoracic adhesions and inflammatory cell infiltrates resulting from the
      traditional surgical approach, an uncomplicated second thoracic incision for
      genetic manipulation is impeded. In this study, we describe a novel surgical
      technique of aortic banding which avoids opening the sternum and thereby avoids
      adhesions and surgery-related inflammation. Placing a clip on the ascending aorta
      using a suprasternal approach in Sprague-Dawley rats created proximal aortic
      constriction. The present study was initiated to determine whether a replication
      deficient adenovirus would enable efficient gene transfer to adult cardiac
      myocytes undergoing hypertrophy and transitioning to heart failure.
      Echocardiography performed at week 24 revealed significant concentric hypertrophy
      and increased fractional shortening followed by LV dilatation with decreased
      fractional shortening after 27 wk of banding. An adenoviral solution encoding for
      the reporter green fluorescent protein gene (GFP) was delivered to the heart.
      Fluorescent microscopy revealed global gene expression throughout hypertrophied
      and failing hearts. Our studies demonstrate that a novel suprasternal approach
      can be applied to create an LV hypertrophy model followed by heart failure which
      also allows investigators to perform genetic manipulations in vivo through gene
      transfer without the complication of adhesions and surgical trauma-induced
      inflammation. Furthermore, our approach to delivery of transgenes results in
      homogenous gene expression in both hypertrophied and failing hearts.

PMID- 11948293
TI  - Laparoscopic versus open surgery for colorectal carcinoma: a prospective clinical
      trial involving 157 cases with a mean follow-up of 5 years.
AB  - The role of laparoscopic resection in the management of colorectal cancer is
      still unclear. It has been shown that laparoscopic colectomies can be
      accomplished with acceptable morbidity. Major concerns are port-site recurrences
      and neoplastic dissemination. The aims of this study were to compare
      perioperative results and long-term outcomes in a prospective, nonrandomized
      study of patients treated by laparoscopic versus open colorectal resection for
      cancer. In particular, the effects of an initial laparoscopic approach on
      survival and recurrence were examined. One hundred fifty-seven patients with
      colorectal carcinoma were included in the prospective trial: 74 underwent
      laparoscopic resection and 83 underwent conventional open surgery. The two groups
      were comparable in terms of characteristics, demographic data, stage of disease,
      and use of adjuvant or palliative chemoradiotherapy. All patients were observed
      at 1.3- and 6-month intervals. The median duration of follow-up was 60 months
      (range, 10-125 months). The mean operating time was significantly longer in the
      laparoscopic group. Six conversions (8.1%) were necessary. The passage of flatus
      and the restarting of oral intake (P = 0.0001) occurred earlier in the
      laparoscopic surgery group than in the open conventional surgery group. The mean
      postoperative stay was significantly shorter in the former group (P = 0.005), as
      was the length of the scar (P = 0.001). There were no deaths in either group. The
      overall morbidity was significantly lower (13% versus 33.7%; P = 0.001) in
      patients treated laparoscopically. No significant differences were observed
      between the groups in the length of specimens, the size of the tumor, or the
      number of nodes removed. Late complications were more frequent after open
      resection (12% versus 5.4%; P = 0.01). Two port-site metastases (2.6%) were seen
      in stage III and IV locally advanced carcinoma. There was no significant
      difference in recurrent disease between the groups (24.3% versus 25%) during the
      60-month follow-up. Stage-for-stage comparisons showed that disease recurrence
      rates and crude death rates were comparable.

PMID- 11948294
TI  - Experience with optical trocar in performing laparoscopic procedures.
AB  - We report on the results of laparoscopic procedures in 1187 patients with use of
      the OPTIVIEW Optical Surgical Obturator, a device that permits visually guided
      trocar entry without insufflation. Most of these procedures (78%) involved hiatal
      hernia repairs, and 51% of our patients had a history of previous abdominal
      procedures. Visualization and pneumoperitoneum were successfully achieved in all
      patients, including those who had previously undergone multiple upper-midline
      abdominal procedures. There were three trocar-related injuries and one late
      complication (0.3%), including two bowel injuries repaired at the time of initial
      surgery, a mesenteric injury repaired with a clip applier, and an incisional
      hernia that resulted from placement of the trocar at midline instead of
      paramedian. Results of this large series indicate that trocar-related
      complications associated with use of the OPTIVIEW trocar are rare.

PMID- 11948295
TI  - Endoscopic resection of benign breast tumors: retromammary space approach.
AB  - Endoscopic surgery is characterized by the creation of a working space. At our
      department, we have obtained good results with a retromammary space approach in
      which the tumor is resected after creation of a working space in the retromammary
      space. The special instruments used for this purpose comprise an endoscopic vein
      harvesting system to dissect the retromammary space, a dissecting balloon to
      compress the space to achieve hemostasis, and laparosonic coagulating shears to
      incise the tumor. This surgical technique provides a superior cosmetic result,
      and the level of patient satisfaction has been high.

PMID- 11948297
TI  - Excluded-loop hepatojejunal anastomosis with use of laparoscopy in late
      management of iatrogenic ligature of the bile duct.
AB  - Although the procedures adopted for bile duct surgery are routine, serious
      complications occasionally occur. This article reports the authors' experience in
      managing an iatrogenic ligature of the bile duct. The patient in this case had
      undergone open cholecystectomy and had significant jaundice in the early
      postoperative period. During the investigation, a complete ligature of the common
      hepatic duct was discovered. An anastomosis of the common hepatic duct with an
      excluded jejunum loop was performed with use of laparoscopy. Periodic follow-up
      continuing until 30 months after surgery showed the patient was asymptomatic, and
      ultrasonography, percutaneous transhepatic cholangiography, and
      cholangioresonance findings were normal. We consider the procedure feasible and
      technically advantageous when done with the assistance of laparoscopy.

PMID- 11948296
TI  - Video-assisted thoracoscopic surgery for diagnosis, staging, and management of
      lung cancer with suspected mediastinal lymphadenopathy.
AB  - The aim of this report was to evaluate the effectiveness of video-assisted
      thoracoscopic surgery (VATS) in staging, diagnosis, and treatment of lung cancer.
      Fifty-two patients were scheduled for mediastinal lymph node VATS biopsy at the
      Oncologic Thoracic Surgery Department of the National Cancer Institute in Milan.
      Fifty patients underwent lymph nodal thoracoscopic biopsy (96%), whereas for the
      other 2 patients, histologic diagnosis was done by pleural metastatic nodule
      thoracoscopic biopsy (4%). We performed 17 lymph nodal biopsies in level 5 (33%),
      14 in level 6 (27%), 12 in level 7 (23%), and 7 in level 8 (13%). No
      postoperative complications were observed, and 19 subjects (36%) underwent open
      lung resection. The histologic diagnosis was adenocarcinoma in 25 cases (48%),
      epidermoid carcinoma in 14 (27%), microcytoma in 9 (17%), and giant-cell lung
      carcinoma in 4 (8%); 10 patients were at stage I (19%), 9 at stage II (17%), 31
      at stage III (60%), and 2 at stage IV (4%). The use of VATS allowed diagnosis of
      the suspected involved mediastinal lymph nodes in lung cancer patients and
      obviated the need for painful thoracotomy, enabling accurate staging and thus
      selection of the optimal treatment.

PMID- 11948298
TI  - Internal hernia as a complication of laparoscopic nissen fundoplication.
AB  - A rare case of strangulated small bowel through a defect in the falciform
      ligament is presented to emphasize the possibility of complication after the
      creation of a window in the falciform ligament during laparoscopic surgery.

PMID- 11948299
TI  - A novel technique for extraction of the appendix in laparoscopic appendectomy.
AB  - A new technique for extraction of the appendix by its retrograde introduction
      into the umbilical port is described. With this technique, appendectomy can be
      undertaken with a single 10-mm and two 5-mm ports.

PMID- 11948300
TI  - Laparoscopic repair of postoperative perineal hernia.
AB  - Symptomatic perineal hernia is a rare complication after abdominoperineal
      resection. Various approaches to surgical repair have been described, including
      transabdominal, transperineal, and combined abdominoperineal repairs. In this
      report, we present a laparoscopic approach for repairing a perineal hernia that
      developed 10 months after laparoscopy-assisted abdominoperineal resection for a
      recurrent squamous cell carcinoma of the anal canal. To the best of our
      knowledge, this is the first report of a laparoscopic repair of perineal hernia.

PMID- 11948301
TI  - Minimally invasive adrenalectomy for pheochromocytoma during pregnancy.
AB  - Pheochromocytoma during pregnancy is a very rare condition; fewer than 200 cases
      have been reported in the literature. We present the case of a 24-year-old
      pregnant woman found to have a pheochromocytoma during investigation of abdominal
      pain. This is the second reported case of laparoscopic adrenalectomy for
      pheochromocytoma detected during pregnancy. After appropriate radiologic
      investigation and medical management, a laparoscopic left adrenalectomy was
      performed at the beginning of the second trimester. There were no complications,
      and she was delivered of a healthy baby at term. We review the management of
      pheochromocytoma in pregnant patients and discuss the role of laparoscopy.

PMID- 11948302
TI  - Robotic-assisted adrenalectomy for adrenal incidentaloma: case and review of the
      technique.
AB  - An incidental left adrenal mass was found in a patient during an evaluation for
      mediastinal widening. The patient had no symptoms attributable to adrenal excess.
      Preoperative biochemical screening was negative for a functioning medullary or
      cortical adrenal tumor. Surgical resection was successfully completed with the
      assistance of the da Vinci robotic system. Pathology demonstrated a rare adrenal
      oncocytoma.

PMID- 11948303
TI  - Transhepatic thrombolysis in acute portal vein thrombosis after laparoscopic
      splenectomy.
AB  - Portal vein thrombosis is a relatively rare clinical entity that can result in
      substantial morbidity and mortality. Because of the risk of intestinal
      infarction, acute symptomatic portal vein thrombosis requires prompt
      intervention. Traditional treatment has included anticoagulation and/or systemic
      thrombolytic therapy. We report the successful management of acute portal vein
      thrombosis with percutaneous transphepatic thrombolytic therapy. In addition to
      the potential for improving regional clot lysis through direct infusion of the
      thrombolytic agent, this method may result in fewer systemic side effects than
      occur with other available treatment modalities.

PMID- 11948304
TI  - Clinical trials and laparoscopic surgery: the second round will require a change
      of tactics.

PMID- 11948305
TI  - Outpatient laparoscopic cholecystectomy.

PMID- 11948308
TI  - A climate for change.

PMID- 11948307
TI  - Empire building: Vienna.

PMID- 11948309
TI  - Rice must be perfectly cooked.

PMID- 11948310
TI  - Ranches blamed over spread of mad deer.

PMID- 11948316
TI  - Chinese institute is an innovation in theory.

PMID- 11948318
TI  - Rice genome sequencers cook up merger.

PMID- 11948321
TI  - Agricultural biotech: the rice squad.

PMID- 11948322
TI  - Computer modelling: our virtual planet.

PMID- 11948323
TI  - How affluence could be good for the environment.

PMID- 11948324
TI  - Training to think globally.

PMID- 11948325
TI  - Hamilton built on work by Haldane and Fisher.

PMID- 11948331
TI  - Chemical synthesis: the art of chemistry.

PMID- 11948332
TI  - Medicine: clearing a path for nerve growth.

PMID- 11948333
TI  - Plant biology: the first harvest of crop genes.

PMID- 11948334
TI  - Geophysics: the disappearing dipole.

PMID- 11948335
TI  - Molecular biology: alternative arrays.

PMID- 11948337
TI  - Global change: carbon dioxide goes with the flow.

PMID- 11948339
TI  - Astronomy: the wanderer returns.

PMID- 11948338
TI  - Immunology: DNA drives autoimmunity.

PMID- 11948341
TI  - Herbivory: caterpillar saliva beats plant defences.
AB  - Blood-feeding arthropods secrete special salivary proteins that suppress the
      defensive reaction they induce in their hosts. This is in contrast to herbivores,
      which are thought to be helpless victims of plant defences elicited by their oral
      secretions. On the basis of the finding that caterpillar regurgitant can reduce
      the amount of toxic nicotine released by the tobacco plant Nicotiana tabacum, we
      investigate here whether specific salivary components from the caterpillar
      Helicoverpa zea might be responsible for this suppression. We find that the
      enzyme glucose oxidase counteracts the production of nicotine induced by the
      caterpillar feeding on the plant.

PMID- 11948342
TI  - Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like
      receptors.
AB  - Autoreactive B cells are present in the lymphoid tissues of healthy individuals,
      but typically remain quiescent. When this homeostasis is perturbed, the formation
      of self-reactive antibodies can have serious pathological consequences. B cells
      expressing an antigen receptor specific for self-immunoglobulin-gamma (IgG) make
      a class of autoantibodies known as rheumatoid factor (RF). Here we show that
      effective activation of RF+ B cells is mediated by IgG2a-chromatin immune
      complexes and requires the synergistic engagement of the antigen receptor and a
      member of the MyD88-dependent Toll-like receptor (TLR) family. Inhibitor studies
      implicate TLR9. These data establish a critical link between the innate and
      adaptive immune systems in the development of systemic autoimmune disease and
      explain the preponderance of autoantibodies reactive with nucleic acid-protein
      particles. The unique features of this dual-engagement pathway should facilitate
      the development of therapies that specifically target autoreactive B cells.

PMID- 11948343
TI  - Scaling of entanglement close to a quantum phase transition.
AB  - Classical phase transitions occur when a physical system reaches a state below a
      critical temperature characterized by macroscopic order. Quantum phase
      transitions occur at absolute zero; they are induced by the change of an external
      parameter or coupling constant, and are driven by quantum fluctuations. Examples
      include transitions in quantum Hall systems, localization in Si-MOSFETs (metal
      oxide silicon field-effect transistors; ref. 4) and the superconductor-insulator
      transition in two-dimensional systems. Both classical and quantum critical points
      are governed by a diverging correlation length, although quantum systems possess
      additional correlations that do not have a classical counterpart. This
      phenomenon, known as entanglement, is the resource that enables quantum
      computation and communication. The role of entanglement at a phase transition is
      not captured by statistical mechanics-a complete classification of the critical
      many-body state requires the introduction of concepts from quantum information
      theory. Here we connect the theory of critical phenomena with quantum information
      by exploring the entangling resources of a system close to its quantum critical
      point. We demonstrate, for a class of one-dimensional magnetic systems, that
      entanglement shows scaling behaviour in the vicinity of the transition point.

PMID- 11948344
TI  - Spontaneous breaking of time-reversal symmetry in the pseudogap state of a high
      Tc superconductor.
AB  - A change in 'symmetry' is often observed when matter undergoes a phase transition
      the symmetry is said to be spontaneously broken. The transition made by
      underdoped high-transition-temperature (high-Tc) superconductors is unusual, in
      that it is not a mean-field transition as seen in other superconductors. Rather,
      there is a region in the phase diagram above the superconducting transition
      temperature Tc (where phase coherence and superconductivity begin) but below a
      characteristic temperature T* where a 'pseudogap' appears in the spectrum of
      electronic excitations. It is therefore important to establish if T* is just a
      cross-over temperature arising from fluctuations in the order parameter that will
      establish superconductivity at Tc (refs 3, 4), or if it marks a phase transition
      where symmetry is spontaneously broken. Here we report that, for a material in
      the pseudogap state, left-circularly polarized photons give a different
      photocurrent from right-circularly polarized photons. This shows that time
      reversal symmetry is spontaneously broken below T*, which therefore corresponds
      to a phase transition.

PMID- 11948345
TI  - Optical studies of solid hydrogen to 320 GPa and evidence for black hydrogen.
AB  - The quest for metallic hydrogen at high pressures represents a longstanding
      problem in condensed matter physics. Recent calculations have predicted that
      solid hydrogen should become a molecular metal at pressures above 300 GPa, before
      transforming into an alkali metal; but the strong quantum nature of the problem
      makes the predictions difficult. Over a decade ago, an optical study of hydrogen
      was made using a diamond anvil cell to reach 250 GPa. However, despite many
      subsequent efforts, quantitative studies at higher pressures have proved
      difficult and their conclusions controversial. Here we report optical
      measurements of solid hydrogen up to a pressure of 320 GPa at 100 K. The vibron
      signature of the H2 molecule persists to at least 316 GPa; no structural changes
      are detected above 160 GPa, and solid hydrogen is observed to turn completely
      opaque at 320 GPa. We measure the absorption edge of hydrogen above 300 GPa,
      observing features characteristic of a direct electronic bandgap. This is at odds
      with the most recent theoretical calculations that predict much larger direct
      transition energies and the closure of an indirect gap. We predict that metal
      hydrogen should be observed at about 450 GPa when the direct gap closes.

PMID- 11948346
TI  - Outgassing from Amazonian rivers and wetlands as a large tropical source of
      atmospheric CO2.
AB  - Terrestrial ecosystems in the humid tropics play a potentially important but
      presently ambiguous role in the global carbon cycle. Whereas global estimates of
      atmospheric CO2 exchange indicate that the tropics are near equilibrium or are a
      source with respect to carbon, ground-based estimates indicate that the amount of
      carbon that is being absorbed by mature rainforests is similar to or greater than
      that being released by tropical deforestation (about 1.6 Gt C yr-1). Estimates of
      the magnitude of carbon sequestration are uncertain, however, depending on
      whether they are derived from measurements of gas fluxes above forests or of
      biomass accumulation in vegetation and soils. It is also possible that
      methodological errors may overestimate rates of carbon uptake or that other loss
      processes have yet to be identified. Here we demonstrate that outgassing
      (evasion) of CO2 from rivers and wetlands of the central Amazon basin constitutes
      an important carbon loss process, equal to 1.2 +/- 0.3 Mg C ha-1 yr-1. This
      carbon probably originates from organic matter transported from upland and
      flooded forests, which is then respired and outgassed downstream. Extrapolated
      across the entire basin, this flux-at 0.5 Gt C yr-1-is an order of magnitude
      greater than fluvial export of organic carbon to the ocean. From these findings,
      we suggest that the overall carbon budget of rainforests, summed across
      terrestrial and aquatic environments, appears closer to being in balance than
      would be inferred from studies of uplands alone.

PMID- 11948347
TI  - Small-scale structure of the geodynamo inferred from Oersted and Magsat satellite
      data.
AB  - The 'geodynamo' in the Earth's liquid outer core produces a magnetic field that
      dominates the large and medium length scales of the magnetic field observed at
      the Earth's surface. Here we use data from the currently operating Danish Oersted
      satellite, and from the US Magsat satellite that operated in 1979/80, to identify
      and interpret variations in the magnetic field over the past 20 years, down to
      length scales previously inaccessible. Projected down to the surface of the
      Earth's core, we found these variations to be small below the Pacific Ocean, and
      large at polar latitudes and in a region centred below southern Africa. The flow
      pattern at the surface of the core that we calculate to account for these changes
      is characterized by a westward flow concentrated in retrograde polar vortices and
      an asymmetric ring where prograde vortices are correlated with highs (and
      retrograde vortices with lows) in the historical (400-year average) magnetic
      field. This pattern is analogous to those seen in a large class of numerical
      dynamo simulations, except for its longitudinal asymmetry. If this asymmetric
      state was reached often in the past, it might account for several persistent
      patterns observed in the palaeomagnetic field. We postulate that it might also be
      a state in which the geodynamo operates before reversing.

PMID- 11948348
TI  - Strong male-driven evolution of DNA sequences in humans and apes.
AB  - Studies of human genetic diseases have suggested a higher mutation rate in males
      than in females and the male-to-female ratio (alpha) of mutation rate has been
      estimated from DNA sequence and microsatellite data to be about 4-6 in higher
      primates. Two recent studies, however, claim that alpha is only about 2 in
      humans. This is even smaller than the estimates (alpha > 4) for carnivores and
      birds; humans should have a higher alpha than carnivores and birds because of a
      longer generation time and a larger sex difference in the number of germ cell
      cycles. To resolve this issue, we sequenced a noncoding fragment on Y of about
      10.4 kilobases (kb) and a homologous region on chromosome 3 in humans, greater
      apes, and lesser apes. Here we show that our estimate of alpha from the internal
      branches of the phylogeny is 5.25 (95% confidence interval (CI) 2.44 to
      infinity), similar to the previous estimates, but significantly higher than the
      two recent ones. In contrast, for the external (short, species-specific)
      branches, alpha is only 2.23 (95% CI: 1.47-3.84). We suggest that closely related
      species are not suitable for estimating alpha, because of ancient polymorphism
      and other factors. Moreover, we provide an explanation for the small estimate of
      alpha in a previous study. Our study reinstates a high alpha in hominoids and
      supports the view that DNA replication errors are the primary source of germline
      mutation.

PMID- 11948349
TI  - Future projections for Mexican faunas under global climate change scenarios.
AB  - Global climates are changing rapidly, with unexpected consequences. Because
      elements of biodiversity respond intimately to climate as an important driving
      force of distributional limitation, distributional shifts and biodiversity losses
      are expected. Nevertheless, in spite of modelling efforts focused on single
      species or entire ecosystems, a few preliminary surveys of fauna-wide effects,
      and evidence of climate change-mediated shifts in several species, the likely
      effects of climate change on species' distributions remain little known, and
      fauna-wide or community-level effects are almost completely unexplored. Here,
      using a genetic algorithm and museum specimen occurrence data, we develop
      ecological niche models for 1,870 species occurring in Mexico and project them
      onto two climate surfaces modelled for 2055. Although extinctions and drastic
      range reductions are predicted to be relatively few, species turnover in some
      local communities is predicted to be high (>40% of species), suggesting that
      severe ecological perturbations may result.

PMID- 11948350
TI  - Extraction of a weak climatic signal by an ecosystem.
AB  - The complexity of ecosystems can cause subtle and chaotic responses to changes in
      external forcing. Although ecosystems may not normally behave chaotically,
      sensitivity to external influences associated with nonlinearity can lead to
      amplification of climatic signals. Strong correlations between an El Nino index
      and rainfall and maize yield in Zimbabwe have been demonstrated; the correlation
      with maize yield was stronger than that with rainfall. A second example is the
      100,000-year ice-age cycle, which may arise from a weak cycle in radiation
      through its influence on the concentration of atmospheric CO2 (ref. 5). Such
      integration of a weak climatic signal has yet to be demonstrated in a realistic
      theoretical system. Here we use a particular climatic phenomenon-the observed
      association between plankton populations around the UK and the position of the
      Gulf Stream-as a probe to demonstrate how a detailed marine ecosystem model
      extracts a weak signal that is spread across different meteorological variables.
      Biological systems may therefore respond to climatic signals other than those
      that dominate the driving variables.

PMID- 11948351
TI  - Direct visuomotor transformations for reaching.
AB  - The posterior parietal cortex (PPC) is thought to have a function in the
      sensorimotor transformations that underlie visually guided reaching, as damage to
      the PPC can result in difficulty reaching to visual targets in the absence of
      specific visual or motor deficits. This function is supported by findings that
      PPC neurons in monkeys are modulated by the direction of hand movement, as well
      as by visual, eye position and limb position signals. The PPC could transform
      visual target locations from retinal coordinates to hand-centred coordinates by
      combining sensory signals in a serial manner to yield a body-centred
      representation of target location, and then subtracting the body-centred location
      of the hand. We report here that in dorsal area 5 of the PPC, remembered target
      locations are coded with respect to both the eye and hand. This suggests that the
      PPC transforms target locations directly between these two reference frames. Data
      obtained in the adjacent parietal reach region (PRR) indicate that this
      transformation may be achieved by vectorially subtracting hand location from
      target location, with both locations represented in eye-centred coordinates.

PMID- 11948352
TI  - Chondroitinase ABC promotes functional recovery after spinal cord injury.
AB  - The inability of axons to regenerate after a spinal cord injury in the adult
      mammalian central nervous system (CNS) can lead to permanent paralysis. At sites
      of CNS injury, a glial scar develops, containing extracellular matrix molecules
      including chondroitin sulphate proteoglycans (CSPGs). CSPGs are inhibitory to
      axon growth in vitro, and regenerating axons stop at CSPG-rich regions in vivo.
      Removing CSPG glycosaminoglycan (GAG) chains attenuates CSPG inhibitory activity.
      To test the functional effects of degrading chondroitin sulphate (CS)-GAG after
      spinal cord injury, we delivered chondroitinase ABC (ChABC) to the lesioned
      dorsal columns of adult rats. We show that intrathecal treatment with ChABC
      degraded CS-GAG at the injury site, upregulated a regeneration-associated protein
      in injured neurons, and promoted regeneration of both ascending sensory
      projections and descending corticospinal tract axons. ChABC treatment also
      restored post-synaptic activity below the lesion after electrical stimulation of
      corticospinal neurons, and promoted functional recovery of locomotor and
      proprioceptive behaviours. Our results demonstrate that CSPGs are important
      inhibitory molecules in vivo and suggest that their manipulation will be useful
      for treatment of human spinal injuries.

PMID- 11948354
TI  - A 'periodic table' for protein structures.
AB  - Current structural genomics programs aim systematically to determine the
      structures of all proteins coded in both human and other genomes, providing a
      complete picture of the number and variety of protein structures that exist. In
      the past, estimates have been made on the basis of the incomplete sample of
      structures currently known. These estimates have varied greatly (between 1,000
      and 10,000; see for example refs 1 and 2), partly because of limited sample size
      but also owing to the difficulties of distinguishing one structure from another.
      This distinction is usually topological, based on the fold of the protein;
      however, in strict topological terms (neglecting to consider intra-chain cross
      links), protein chains are open strings and hence are all identical. To avoid
      this trivial result, topologies are determined by considering secondary links in
      the form of intra-chain hydrogen bonds (secondary structure) and tertiary links
      formed by the packing of secondary structures. However, small additions to or
      loss of structure can make large changes to these perceived topologies and such
      subjective solutions are neither robust nor amenable to automation. Here I
      formalize both secondary and tertiary links to allow the rigorous and automatic
      definition of protein topology.

PMID- 11948353
TI  - Dissecting glucose signalling with diversity-oriented synthesis and small
      molecule microarrays.
AB  - Small molecules that alter protein function provide a means to modulate
      biological networks with temporal resolution. Here we demonstrate a potentially
      general and scalable method of identifying such molecules by application to a
      particular protein, Ure2p, which represses the transcription factors Gln3p and
      Nil1p. By probing a high-density microarray of small molecules generated by
      diversity-oriented synthesis with fluorescently labelled Ure2p, we performed
      3,780 protein-binding assays in parallel and identified several compounds that
      bind Ure2p. One compound, which we call uretupamine, specifically activates a
      glucose-sensitive transcriptional pathway downstream of Ure2p. Whole-genome
      transcription profiling and chemical epistasis demonstrate the remarkable Ure2p
      specificity of uretupamine and its ability to modulate the glucose-sensitive
      subset of genes downstream of Ure2p. These results demonstrate that diversity
      oriented synthesis and small-molecule microarrays can be used to identify small
      molecules that bind to a protein of interest, and that these small molecules can
      regulate specific functions of the protein.

PMID- 11948357
TI  - Recently discovered blood-borne viruses.
AB  - In recent years, molecular biology advances have enabled many investigators to
      discover a number of viruses that have been difficult to characterise by cell
      culture techniques. Two blood-borne viruses have been identified. These are GB
      virus C (GBV-C) and TT virus (TTV). GBV-C was discovered in 1995. It is a
      flavivirus-like enveloped particle measuring 50-100 nm in diameter with a density
      of 1.08-1.13 g/cm3. The genome of GBV-C is a single-stranded, positive strand
      ribonucleic acid of approximately 8600 nucleotides. The TTV was discovered in
      1997. It is a circular single-stranded deoxyribonucleic acid virus, non-enveloped
      of approximately 3900 nucleotides. It has a density of 1.31-1.34 g/cm3 and a
      particle size of 30-50 nm. Both viruses are distributed widely throughout the
      world. Most GBV-C infections are asymptomatic, transient and self-limiting. To
      date, solid evidence for any association of TTV with disease has not been
      demonstrated.

PMID- 11948358
TI  - Type B and D viral hepatitis: epidemiological changes in Southern Europe.
AB  - The incidence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection is
      in rapid decline in Southern Europe, due to the improvement in hygiene and
      economic conditions and the vaccination campaigns against hepatitis B. These
      changes have led to a shift from the classic form of chronic hepatitis B due to
      the wild-type virus, expressing hepatitis B e antigen (HBeAg) to a liver disease
      due to a mutated virus which does not express the HBeAg (e-minus mutant). Very
      interestingly, HBV-DNA has been detected in the liver tissue and in the serum of
      some subjects who lack hepatitis B surface antigen (HBsAg) in serum. This
      "occult" infection may be responsible for the residual cases of acute hepatitis B
      and might influence the course of chronic liver diseases of different
      aetiologies. A further consequence of the control of HBV infection is a
      spectacular decline in HDV circulation. At present only 8% of the HBsAg carriers
      in Italy have anti-HDV antibodies, vs 23% in 1987. Most of the patients with HDV
      infection are over 40 and present a mild liver disease or a slowly progressive
      cirrhosis. These epidemiological data support the concept that the
      epidemiological changes influence the clinical pattern of chronic hepatitis.

PMID- 11948359
TI  - Hepatitis B: therapeutic perspectives.
AB  - Therapy with interferon (IFN), an immunomodulant with anti-viral activities, is
      efficacious only in a minority of chronic hepatitis B (CHB); it is more
      efficacious in the hepatitis B e antigen (HBeAg)-positive variety sustained by
      the wild type hepatitis B virus (HBV) than in the HBeAg-negative variety
      sustained by mutant forms of the virus. Several other therapeutic approaches were
      attempted in recent years. The most promising is therapy with synthetic
      nucleosides as anti-virals capable of blocking the replicative activity of the
      HBV. Lamivudine (LAM) is the first of this class of compounds that has entered
      clinical use. It is well tolerated and highly effective in inhibiting HBV and
      abate HBV-related inflammation both in the HBeAg positive and negative variety of
      CHB. In the HBeAg positive variety it induces sero-conversion to anti-HBe at a
      rate that linearly increases over the years, reaching 40% at the third year. In
      the HBeAg-negative variety maintenance of viral repression requires continuative
      therapy. A major drawback of continued LAM therapy is the risk of the emergence
      of mutants in the tyrosine-methionine-aspartate-aspartate locus of the polymerase
      gene. These mutants are no longer responsive to LAM and may rekindle disease;
      wild type HBV and related disease often return after suspension of therapy. Other
      anti-viral drugs, the prototype of which is adefovir, are currently under
      clinical investigation in CHB as monotherapy or complementary therapy to LAM.

PMID- 11948360
TI  - Hepatitis C: therapeutic perspectives.
AB  - Continuous efforts are vital to develop new treatment strategies to improve
      sustained response rates, especially for difficult to treat patients infected
      with the hepatitis C virus. Despite the introduction of ribavirin, more than 50%
      of the patients do not eliminate the virus with the current standard therapy of
      interferon-a (IFN) and ribavirin. Options to further enhance response rates
      include modification of the IFN-dosing schedule with daily dosing of IFN, new IFN
      such as consensus interferon or modified IFN with longer half-life and more
      favourable pharmacokinetics such as pegylated IFN (PEG-IFN). Clinical trials with
      new IFN showed that consensus IFN may improve response rates in unsuccessfully
      pre-treated patients and patients with HCV-genotype-1. Treatments with PEG-IFN
      will double response rates achieved with standard IFN monotherapy. The
      combination of PEG-IFN and ribavirin improves the virological response to more
      than 50% and even to more than 80% in patients with genotype 2 or 3. By now,
      standard therapy of chronic hepatitis C has been changed to the combination of
      PEG-IFN plus ribavirin. Future anti-viral drugs may comprise molecules that
      directly inhibit HCV proteins and interfere with viral replication. NS3/4A serine
      protease, ribonucleic acid (RNA) helicase, RNA-dependent RNA polymerase may be
      potential targets for new drugs. Furthermore antisense oligonucleotides or
      ribozymes may become new treatment options to inhibit HCV replication. Finally,
      immunotherapies to enhance HCV-specific immune responses are also attractive
      strategies to control HCV infection and to prevent chronic liver disease.

PMID- 11948361
TI  - Global epidemiology and medical aspects of hepatitis E.
AB  - Hepatitis E is a self-limited enterically transmitted acute viral hepatitis that
      occurs frequently in epidemic outbreaks and as sporadic hepatitis in the Indian
      sub-continent, Southeast and Central Asia, the Middle East, parts of Africa, and
      Mexico. Hepatitis E virus (HEV) is excreted in faeces and is transmitted
      predominantly by the faecal-oral route, usually through contaminated water. The
      reservoir of the virus during the inter-epidemic periods in disease-endemic
      countries may reside in the environment, in sub-clinically HEV-infected humans,
      and/or animals infected with an HEV-like virus. Chronic infection is unknown.
      Diagnosis of HEV infection is usually made by detection of anti-HEV antibodies or
      HEV-RNA in patients  serum specimens. Clinical illness due to HEV infection is
      similar to other forms of viral hepatitis except in pregnant women, in whom the
      illness is particularly severe with a mortality as high as 25%. Asymptomatic and
      anicteric infections may occur. No specific treatment is available, and the most
      effective mode of preventing this disease is use of clean water and proper
      sanitation. Recombinant vaccines are being developed that may be particularly
      useful for travellers to the disease-endemic areas and for pregnant women.

PMID- 11948362
TI  - Granulocyte elastase release and pulmonary hemodynamics in patients with mitral
      valvular disease.
AB  - In patients with atrial septal defect in whom pulmonary hypertension could
      develop as a consequence of left-to-right shunt, the extent of neutrophil
      mediated lung injury induced by cardiopulmonary bypass (CPB) is related to the
      degree of increase in the preoperative pulmonary artery pressure. In the present
      study, we investigated the relationship between levels of granulocyte elastase
      (GEL) after CPB and preoperative pulmonary hemodynamics or changes in pulmonary
      function after the operation in patients with mitral valve disease, in whom
      pulmonary hypertension could develop as a result of pulmonary venous congestion.
      The plasma levels of GEL were measured before and after CPB in patients who
      underwent mitral valve replacement. Respiratory index (RI) was evaluated
      preoperatively and postoperatively. Preoperative pulmonary hemodynamics were
      determined within one month of the operation. Granulocyte elastase level rose
      significantly after CPB from baseline (134.3 +/- 44.6 mg/L versus 2042.1 +/-
      1215.0 mg/L; p <0.001). Peak level of GEL was significantly correlated with
      preoperative systolic pulmonary artery pressure (r = 0.71; p = 0.020), mean
      pulmonary artery pressure (r = 0.64; p = 0.046), pulmonary capillary wedge
      pressure (r = 0.68; p = 0.032), and pulmonary-to-systemic arterial pressure ratio
      (r = 0.64; p = 0.045), but not with the hemodynamic variables for pulmonary blood
      flow or pulmonary resistance. Moreover, the value of (Postoperative RI -
      Preoperative RI)/Preoperative RI was positively correlated with the peak level of
      GEL (r = 0.76; p = 0.011). In conclusion, in patients with mitral valvular
      disease, as in those with atrial septal defect, the increase in GEL level after
      CPB is proportional to the increase in preoperative pulmonary artery pressure,
      which may cause the accordant pulmonary vascular damage.

PMID- 11948363
TI  - Molecular regulation of Na+-K+-2Cl- cotransporter (NKCC1) and epithelial chloride
      secretion.
AB  - Defective regulation of epithelial secretion underlies the clinical
      manifestations of a number of important human diseases ranging from cystic
      fibrosis to secretory diarrhea. Although much attention has focused on the role
      of apical membrane chloride (Cl-) channels in this process, emerging evidence
      highlights the importance of a basolateral Na+-K+-2Cl- cotransporter (NKCC1) as
      an independent regulatory site that may determine the overall rate of epithelial
      secretion. The cotransporter NKCC1 is expressed not only in epithelial cells but
      also in virtually all mammalian cells, where it plays a more generalized role in
      cell volume homeostasis, cell ionic composition, and, possibly, the control of
      cell growth. Emerging molecular evidence indicates that NKCC1 function is
      regulated in the short and long term at the level of protein phosphorylation,
      membrane targeting, and gene expression. An improved understanding of NKCC1 may
      lead to new therapeutic approaches to secretory diarrhea as well as diverse
      clinical conditions in which cell ion composition is disturbed.

PMID- 11948364
TI  - DNA and RNA modified dendritic cell vaccines.
AB  - The purpose of this paper is to describe the strategies for genetic modification
      of dendritic cells for use in active immunotherapy for the treatment of
      malignancies. An accruing body of data supports the concept of directing a
      therapeutic immune response, mediated by the cellular arm of the immune system,
      against cancers in vivo. Dendritic cells are the most potent inducers of T cell
      mediated immune responses against tumor-expressed antigens, by virtue of their
      ability to present tumor antigens in the context of major histocompatibility
      molecules to naive T cells with receptors specific for the antigen. A variety of
      methods for directing antigens to the MHC molecules of dendritic cells and
      augmenting their T cell stimulatory activity have been developed. This paper
      describes one group of promising strategies, the genetic modification of
      dendritic cells to direct the expression of tumor antigens, costimulatory
      molecules, and stimulatory cytokines. Genetic modification can be effected by
      either DNA or RNA, and the genetic material may be delivered by vectors or by
      physical means. These approaches are now entering human clinical trials.

PMID- 11948365
TI  - Molecular pathways of regeneration and repair after liver transplantation.
AB  - Injury to liver grafts due to cold ischemia, preservation, and reperfusion
      continues to be an important factor in patient outcome after liver
      transplantation. The development of therapeutic interventions that can limit
      ischemic injury, enhance recovery, and improve early graft function can have a
      major impact on patient morbidity. The mechanisms of hepatic preservation and
      reperfusion injury, the molecular pathways of graft recovery, and the cells
      involved remain poorly understood. With significant damage to parenchymal tissue
      following cold ischemic injury comes the need for replacement or repair of
      injured cells. In a rat liver transplant model, expression of cytokines and
      activation of transcription factors associated with the cell cycle resulting in
      cellular replication correlates with the length of cold ischemia and the degree
      of damage. The resident liver macrophage, the Kupffer cell, has been implicated
      as the primary source of inflammatory factors but may also be the source of
      important growth factors and cytokines that initiate cellular recovery and
      regeneration. Determining the source of the initiating signal is important, as
      manipulation of this signal can be used for therapeutic interventions in such
      fields as transplantation, tumor immunology, and inflammatory disease. These
      studies demonstrate the critical interrelation between parenchymal cells and
      cells of the immune system during signaling and recovery from preservation and
      reperfusion injury in the liver. Further defining the role of these immune cells
      and their products during the initiation of cellular recovery is essential for
      developing strategies to improve hepatocellular function after injury.

PMID- 11948366
TI  - Molecular biology of endotoxin antagonism.
AB  - The development of new therapies for the treatment of gram-negative bacterial
      sepsis has been the focus of extensive investigation. Molecular and cellular
      biologic techniques have led to important advances, including (1) identification
      of naturally occurring lipopolysaccharide (LPS)-binding proteins; (2) generation
      of novel LPS-binding antibodies, proteins, and peptides; and (3) characterization
      of the molecular determinants of LPS binding. In composite, these advances have
      facilitated comprehension of the manner in which gram-negative bacterial
      infection and concurrent endotoxemia exert detrimental effects on the mammalian
      host. The purpose of this review was to examine recent information regarding
      molecular determinants of LPS binding and the initial cellular signal
      transduction events, which lead to the local and systemic cytokine response and
      sepsis syndrome. Concurrently, the status of studies examining the effects of
      various endotoxin antagonists is reviewed. Data from these studies provide an
      indication of potential sites for therapeutic intervention as well as
      increasingly detailed understanding of the molecular mechanism of endotoxin
      antagonism. Taken together, these advances can be expected to further the
      development of the next generation of novel, adjuvant therapies for the treatment
      of sepsis syndrome caused by gram-negative bacterial infection and endotoxemia.

PMID- 11948368
TI  - Cyclin D3 is essential for intestinal epithelial cell proliferation.
AB  - Intestinal epithelium is a complex organ that undergoes continuous proliferation.
      D-type cyclins bind cyclin-dependent kinases (Cdk4 and Cdk6) and are expressed
      during the transition from G0 into the S phase. Previously, we reported that
      cyclins D1 and D3 are induced by growth factors in two rat intestinal epithelial
      cell lines, IEC-6 and RIE-1. However, transforming growth factor beta induces G1
      arrest in both intestinal cell lines without inhibiting cyclin D3, suggesting
      that cyclin D3 may not have essential functions in the gut. In the present study,
      we determined whether cyclin D3 is required for the transition from G0 into the S
      phase in intestinal epithelial cells. Microinjection of anti-cyclin D3 antiserum
      inhibited quiescent IEC-6 and RIE-1 cells from entering the S phase, while cells
      microinjected with a nonspecific mouse immunoglobin G continued to progress into
      the S phase. We also examined the expression of cyclin D3 in rat jejunal mucosa
      after fasting and refeeding. Cyclin D3 levels were not altered by fasting and
      refeeding; however, Cdk4 expression was suppressed by fasting and returned to
      control levels after refeeding. Our results suggest that cyclin D3 is essential
      for intestinal epithelial cell proliferation, although its expression is not
      regulated by dietary restriction.

PMID- 11948367
TI  - Current progress in suicide gene therapy for cancer.
AB  - Standard chemotherapeutic agents and ionizing radiation destroy dividing cells.
      Because tumor cells divide more rapidly than normal cells, there is a therapeutic
      index in which damage to the cancer cells is maximized while keeping the toxicity
      to the normal host cells acceptable. Suicide gene therapy strives to deliver
      genes to the cancer cells, which convert nontoxic prodrugs into active
      chemotherapeutic agents. With this strategy, the systemically administered
      prodrug is converted to the active chemotherapeutic agent only in cancer cells,
      thereby allowing a maximal therapeutic effect while limiting systemic toxicity. A
      literature search was conducted using the MEDLINE database from 1990 to 2001 to
      identify articles related to suicide gene therapy for cancer. A number of suicide
      gene systems have been identified, including the herpes simplex virus thymidine
      kinase gene, the cytosine deaminase gene, the varicella-zoster virus thymidine
      kinase gene, the nitroreductase gene, the Escherichia coli gpt gene, and the E.
      coli Deo gene. Various vectors, including liposomes, retroviruses, and
      adenoviruses, have been used to transfer these suicide genes to tumor cells.
      These strategies have been effective in cell culture experiments, laboratory
      animals, and some early clinical trials. Advances in tissue- and cell-specific
      delivery of suicide genes using specific promoters will improve the clinical
      utility of suicide gene therapy.

PMID- 11948369
TI  - New strategies for colorectal cancer prevention and treatment.
AB  - Colorectal cancer (CRC) is the second most common fatal malignancy in the Western
      world, with more than 150,000 new cases accounting for 55,000 deaths in the
      United States every year. Surgical resection is an effective treatment for
      localized disease, achieving a 5-year survival rate of 90%; but chemotherapy and
      other novel treatments for metastatic disease remain ineffective. There have been
      significant efforts to identify risk factors associated with the development of
      CRC and to explore potential preventive therapies. Both genetic and epigenetic
      factors contribute to the development of colorectal cancer. Specific genetic
      changes in proto-oncogenes, tumor suppressor genes, and DNA mismatch repair genes
      have led to a genetic model of CRC. Cooperative genetic aberrations involving APC
      (adenomatous polyposis coli), beta-catenine, K-ras, and p53 are involved in the
      multistep adenoma-carcinoma sequence of CRC. Emerging data have implicated
      cyclooxygenase-2 (COX-2) and prostanoid production in the pathogenesis of
      colorectal carcinoma. Several reports indicate a close relation between the
      intake of nonsteroidal antiinflammatory drugs (NSAIDs) and a decreased risk for
      developing colorectal cancer. Epidemiologic studies indicate a 40% to 50%
      reduction in mortality due to colorectal cancer in individuals taking NSAIDs
      (e.g., aspirin). Epigenetic factors including age, diet, angiogenesis, and immune
      responses also appear to contribute to the development of CRC. Combining
      knowledge of the genetic and epigenetic events implicated in this disease may
      allow a broader understanding of the pathogenesis of CRC. These developments may
      yield benefits in earlier detection and in the design of better antitumor
      interventions.

PMID- 11948370
TI  - Stress and vascular disease at the cellular and molecular levels.
AB  - The role of nitric oxide in mediating smooth muscle relaxation is well
      established. Less is known about the downstream signaling events inside the
      smooth muscle cell that produce relaxation of the contractile machinery. One
      possible effector molecule is the small heat shock protein HSP20. Increased
      phosphorylation of HSP20 is associated with vasorelaxation. HSP20 is associated
      with elements of the contractile machinery such as another small heat shock
      protein (HSP27), actin, and myosin. Thus HSP20 may mediate vasorelaxation by
      directly modulating cytoskeletal or contractile elements in muscle cells.

PMID- 11948371
TI  - Role of nitric oxide and peroxynitrite in gut barrier failure.
AB  - Bacterial translocation (BT) may be a normal physiologic process that is
      important for mucosal antigen sampling in the gut. However, physiologic insults
      such as endotoxemia, hemorrhagic shock, or necrotizing enterocolitis (NEC) may
      lead to pathologic BT and thus contribute to the pathogenesis of nosocomial
      infection. The mechanism may involve accelerated enterocyte apoptosis at the
      intestinal villus apex resulting, at least transiently, in a "bare area" at the
      villus tip where bacteria can attach and traverse the epithelium. Evidence
      suggests that sustained upregulation of the inducible isoform of nitric oxide
      synthase (NOS-2) co-localizes with enterocyte apoptosis and immunoreactivity to 3
      nitrotyrosine, the footprint of peroxynitrite (ONOO-), a potent oxidant formed by
      the reaction of nitric oxide (NO) with superoxide. We propose that the bare area
      at the villus apex is caused by apoptosis of enterocytes that have migrated from
      the base of the crypts to the villus apex and are shed into the intestinal lumen.
      These bare areas, and thus the degree of BT, may be the result of an imbalance
      between enterocyte proliferation and apoptosis. We postulate that normal
      enterocyte apoptosis is mediated by the caspase cascade, whereas enterocyte
      proliferation and differentiation in the crypt may be regulated by tyrosine
      kinase-dependent signaling pathways. Both of these cellular pathways may be
      influenced by overproduction of NO and its metabolite ONOO-. Therefore, sustained
      NO production and ONOO- formation occurring in inflammatory states may
      differentially accelerate apoptosis in the villus apex and/or inhibit
      proliferation at the base of the crypts resulting in expanded extrusion zones at
      the villus tip and accelerated BT.

PMID- 11948372
TI  - Enhanced transgene expression in primitive hematopoietic progenitor cells and
      embryonic stem cells efficiently transduced by optimized retroviral hybrid
      vectors.
AB  - Oncoretroviral vectors have been successfully used in gene therapy trials, yet
      low transduction rates and loss of transgene expression are still major obstacles
      for their application. To overcome these problems we modified the widely used
      Moloney murine leukemia virus-derived retroviral vector pMX by replacing the
      3'LTR with the spleen focus-forming virus LTR and inserting the woodchuck
      hepatitis B virus post-translational regulatory element. To compare requirements
      crucial for efficient transgene expression, we generated the hybrid retroviral
      vectors pMOWS and pOWS that harbor the complete murine embryonic stem cell virus
      (MESV)-leader sequence or a shortened MESV-leader not comprising primer binding
      site (PBS) and splice donor (SD). Applying these retroviral vectors significantly
      augmented transgene expression in hematopoietic cell lines and progenitor cells.
      For transduction of murine embryonic stem (ES) cells the retroviral vector pMOWS
      that harbors the MESV-PBS and -SD was superior resulting in 65% green fluorescent
      protein (GFP) expressing ES cells. Surprisingly, in murine and human primitive
      hematopoietic progenitor cells (HPC), the highest efficiency of up to 66% GFP
      expressing cells was achieved with pOWS, a retroviral vector that retains the
      negative regulatory element coinciding with the MoMuLV-PBS. In summary our hybrid
      retroviral vectors facilitate significantly improved transgene expression in
      multipotent cells and thus possess great potential for reconstituting genes in
      primary cells of disease models, as well as for gene therapy.

PMID- 11948373
TI  - Molecular strategy using cis-element 'decoy' of E2F binding site inhibits
      neointimal formation in porcine balloon-injured coronary artery model.
AB  - Transcription factor E2F plays a pivotal role in the transactivation of cell
      cycle regulatory genes, leading to vascular lesion formation. Double-stranded DNA
      with high affinity for E2F as 'decoy' cis elements may block the activation of
      genes mediating the cell cycle, resulting in an effective therapeutic agent for
      treating intimal hyperplasia. In this study, we tested the feasibility of E2F
      decoy therapy to treat neointimal formation in a porcine coronary artery balloon
      injury model. An angioplasty catheter was inserted in the left anterior
      descending coronary artery of pigs to cause vascular injury. Initially, we tested
      the feasibility of transfection of FITC-labeled E2F decoy ODN using a hydrogel
      balloon catheter. Fluorescence due to E2F decoy ODN could be detected throughout
      the medial layer. Therefore, we transfected E2F decoy ODN into the balloon
      injured artery using hydrogel catheter. Of importance, intravascular ultrasound
      (IVUS) and histological evaluation demonstrated that plaque area in the balloon
      injured artery was significantly reduced by E2F decoy ODN compared with
      mismatched decoy ODN at 1 month after a single transfection (P < 0.01). In
      contrast, luminal and total vessel areas were significantly increased in vessels
      treated with E2F decoy ODN as compared with mismatched decoy. Endothelial
      function after angioplasty was not affected by E2F decoy transfection. Finally,
      we tested the acute toxicity of E2F decoy ODN in monkeys, and no apparent side
      effects were detected. Here, we report the successful in vivo transfer of E2F
      decoy ODN using a hydrogel catheter to inhibit vascular lesion formation in
      balloon-injured porcine coronary artery without any apparent side-effects.

PMID- 11948374
TI  - Introduction of DNA enzyme for Egr-1 into tubulointerstitial fibroblasts by
      electroporation reduced interstitial alpha-smooth muscle actin expression and
      fibrosis in unilateral ureteral obstruction (UUO) rats.
AB  - The phenotypic alteration of interstitial fibroblasts into 'myofibroblasts',
      acquiring characteristics of both fibroblasts and smooth muscle cells is a key
      event in the formation of tubulointerstitial fibrosis. The up-regulation of the
      early growth response gene 1 (Egr-1) preceded the increased interstitial
      expression of alpha-smooth muscle actin (alphaSMA), a marker of phenotypic
      changes, in obstructed kidney, a model of interstitial fibrosis. To target Egr-1
      expression in the interstitium of obstructed kidneys, we introduced a DNA enzyme
      for Egr-1 (ED5) or scrambled DNA (SCR) into interstitial fibroblasts by
      electroporation-mediated gene transfer. Northern blot analysis confirmed an
      increase in the cortical mRNA expression of Egr-1 in the obstructed kidneys from
      untreated or SCR-treated rats, while ED5 transfection blocked Egr-1 expression
      with a concomitant reduction in TGF-beta, alphaSMA and type I collagen mRNA
      expression. Consequently, ED5 inhibited interstitial fibrosis. In conclusion,
      electroporation-mediated retrograde gene transfer can be an ideal vehicle into
      interstitial fibroblasts, and molecular intervention of Egr-1 in the interstitium
      may become a new therapeutic strategy for interstitial fibrosis.

PMID- 11948375
TI  - Prime-boost vaccines encoding an intracellular idiotype/GM-CSF fusion protein
      induce protective cell-mediated immunity in murine pre-B cell leukemia.
AB  - Two vaccines against an intracellularly expressed B cell idiotype were assessed
      for their ability to induce protective immunity in mice against challenge with a
      pre-B cell leukemia. One vaccine was based on a plasmid expression vector and the
      other was a recombinant vaccinia virus; both vaccines expressed a polypeptide
      derived from the complementarity-determining regions (CDR(2)-CDR(3)) of the
      leukemic clone-specific immunoglobulin heavy chain (IgH), as a fusion product
      with mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF). Mice
      inoculated with either vaccine showed significantly higher survival rates than
      controls after challenge with leukemia cells. However, protection from tumor
      challenge was optimal when the DNA vaccine was used for priming, followed by a
      booster immunization with the vaccinia virus recombinant. This vaccination
      protocol induced resistance not only to the first tumor challenge given shortly
      afterwards, but also to a second challenge given months later. Both CD4(+) and
      CD8(+) T cells contributed to protection in vaccinated mice. These data suggest
      that such a vaccine regimen might reduce the incidence of recurrence in patients
      with minimal residual disease after conventional therapy.

PMID- 11948376
TI  - A novel bystander effect involving tumor cell-derived Fas and FasL interactions
      following Ad.HSV-tk and Ad.mIL-12 gene therapies in experimental prostate cancer.
AB  - To enhance the NK population induced by Herpes Simplex virus thymidine kinase
      (HSV-tk) gene transduction and ganciclovir (GCV) treatment, adenovirus-mediated
      (Ad) expression of IL-12 was added to Ad.HSV-tk + GCV as combination gene
      therapy. This approach resulted in improved local and systemic growth suppression
      in a metastatic model of mouse prostate cancer (RM-1). In vitro assay of tumor
      infiltrating lymphocytes noted superior lysis of both RM-1 and Yac-1 targets with
      combination therapy, but in vivo depletion of NK cells only negatively impacted
      on systemic growth inhibition. TUNEL assay of primary tumors noted induction of
      apoptosis between two and four times higher than controls lasting for 6-8 days
      post-vector injection. After demonstrating that Ad.HSV-tk/GCV and Ad.mIL-12
      induced IFN-gamma independently up-regulated expression of FasL and Fas,
      respectively, studies examined tumor cell-mediated death through Fas/FasL-induced
      apoptosis as a mechanism of primary tumor growth suppression. In vitro,
      combination therapy at low vector doses resulted in synergistic growth
      suppression, which could be negated by the addition of anti-FasL antibody. In
      vivo co-inoculation of an adenovirus expressing soluble Fas resulted in
      combination therapy-treated tumors, which were three times larger than expected,
      and a reduction in apoptosis to baseline levels. In FasL knockout mice,
      combination therapy maintained the superior results experienced in wild-type
      mice, indicating that tumor cell, not host cell FasL, was responsible for Fas
      transactivation. Therefore, the combination of Ad.HSV-tk/GCV + Ad.mIL-12 results
      in enhanced local growth control via apoptosis due to tumor cell expression of
      Fas and FasL and improved anti-metastatic activity secondary to a strong NK
      response.

PMID- 11948377
TI  - Retroinfusion of NFkappaB decoy oligonucleotide extends cardioprotection achieved
      by CD18 inhibition in a preclinical study of myocardial ischemia and
      retroinfusion in pigs.
AB  - Myocardial reperfusion injury is partially mediated by postischemic inflammation.
      Beyond acute PMN recruitment, postischemic inflammation comprises subacute PMN
      adhesion, eg via NFkappaB activation. In a pig model of 60-min LAD occlusion by
      PTCA ballon inflation and 1 to 7 days of reperfusion, we investigated the impact
      of targeted NFkappaB decoy oligonucleotide (ODN) transfection in the area at risk
      (AAR) on infarct size and regional myocardial function. After 55 min of LAD
      occlusion, liposomes containing NFkappaB ODN were selectively retroinfused into
      the anterior interventricular vein for 5 min. Then, retroinfusion was stopped and
      reperfusion was initiated. Where indicated, CD18 antibody IB4 was infused
      systemically at 30 min of ischemia. Methylen blue and tetrazolium-red staining
      were used for quantification of the infarct size. Subendocardial segment
      shortening (SES) by sonomicrometric crystals in infarct area and AAR was assessed
      under pacing (expressed as % of control region). NFkappaB decoy ODN retroinfusion
      reduced infarct size (36 +/- 4% versus 49 +/- 5% in control hearts at day 7),
      whereas functional reserve of the AAR (SES 73 +/- 17% versus 46 +/- 18% at
      180/min) tended to improve. Similar effects were observed after IB4 infusion (38
      +/- 5% infarct size, 85 +/- 7% SES at 180/min). A combination of NFkappaB decoy
      ODN retroinfusion and IB4 infusion further decreased infarct size (26 +/- 2%) and
      improved functional reserve (SES 94 +/- 6% at 180/min). We conclude that NFkappaB
      decoy ODN transfection by retroinfusion is feasible in pig hearts and provides
      postischemic cardioprotection in addition to CD18 blockade.

PMID- 11948378
TI  - Retroviral transduction of human peripheral blood lymphocytes with Bcl-X(L)
      promotes in vitro lymphocyte survival in pro-apoptotic conditions.
AB  - The prolonged in vivo survival of genetically modified effector cells is crucial
      to the success of any (gene-modified) adoptive cellular immunotherapy approach.
      In cancer clinical trials to date, however, the detection of surviving
      circulating gene-modified T cells has required highly sensitive techniques. In
      vitro studies of T cell co-stimulation have shown that up-regulation of the anti
      apoptosis gene Bcl-X(L) by ligation of CD28 promotes T cell survival, but not
      proliferation. Here we have investigated the ability to modulate resistance to
      apoptosis and improve cell survival by transducing human peripheral blood
      lymphocytes using a retroviral vector that expresses Bcl-X(L). We show that
      Jurkat cells transduced with Bcl-X(L) retrovirus were partially resistant to Fas
      (CD95) antibody-induced apoptosis. Subsequent in vitro assays with transduced
      primary human lymphocytes demonstrates that over-expression of Bcl-X(L) promotes
      the survival of lymphocytes cultured in the absence of interleukin-2. Activation
      induced apoptosis with anti-CD3(epsilon) antibody, OKT3 is also modulated.
      Furthermore, Bcl-X(L) over-expression in human lymphocytes delays the onset of
      apoptosis induced by long-term co-culture with tumour cell lines. Despite this
      improved in vitro survival, in a preliminary experiment to assess safety, no
      signs of malignancy or autoimmunity were observed in NOD/SCID mice injected with
      Bcl-X(L) transduced lymphocytes. These results indicate that expression of Bcl
      X(L) in lymphocyte therapy either alone or in conjunction with an additional
      therapeutic gene could enhance persistence of cells in vivo thereby potentially
      improving the clinical outcome of adoptive cellular therapy.

PMID- 11948379
TI  - Always caring, especially when cure is not possible--an essential tenet of
      neonatal care.

PMID- 11948380
TI  - Creation of a neonatal end-of-life palliative care protocol.
AB  - OBJECTIVE: To create a protocol delineating the needs of patients, families, and
      staff necessary to provide a pain-free, dignified, family-, and staff-supported
      death for newborns who cannot benefit from intensive, life-extending,
      technological support. STUDY DESIGN: Using Internet e-mail, a Delphi study with
      sequential questionnaires soliciting participant response, investigator analysis,
      and follow-up responses from participants was conducted to build a consensus
      document. Institutional review was granted and respondents gave consent.
      Recruitment was conducted at medical, ethics, nursing, and multidisciplinary
      organization meetings. Synthesis of 16 palliative care/end-of-life protocols
      developed by regional, institutional, and parent organizations was included.
      Participants from 93 locations in the US and 4 abroad gave feedback to 13
      questions derived from clinical experience and the literature. The data underwent
      four rounds of analysis with 95% retention of the 101 participants over an 18
      month period. RESULTS/CONCLUSION: Specific consensus-based recommendations are
      presented with a description of palliative care; categories of candidates;
      planning and education needed to begin palliative care services; relationships
      between community and tertiary centers; components of optimally supported
      neonatal death; family care, including cultural, spiritual, and practical needs;
      ventilator withdrawal, including pain and symptom management; recommendations
      when death does not occur after cessation of life-extending interventions; family
      follow-up care; and necessary ongoing staff support.

PMID- 11948381
TI  - A randomized trial of inhaled versus intravenous steroids in ventilator-dependent
      preterm infants.
AB  - OBJECTIVE: Intravenous steroids improve the respiratory course in ventilator
      dependent preterm infants but have adverse effects. We hypothesized that inhaled
      steroids would be as effective, but with less systemic effects. STUDY DESIGN: We
      conducted a randomized, prospective trial comparing inhaled beclomethasone,
      either 400 or 800 microg/d, to intravenous dexamethasone in preterm infants
      dependent on conventional mechanical ventilation and supplemental oxygen at 2
      weeks of age. RESULTS: Seventy-eight infants were randomized. By day three of
      therapy, the intravenous steroid group had significantly decreased ventilator and
      oxygen requirements compared to either inhaled group. The inhaled 800-microg/d
      group trended toward more rapid decreases in ventilator and oxygen requirements
      than the 400-microg/d group. By day 14, all groups had similar reductions in
      ventilator and oxygen requirements. The incidence of adverse effects did not
      differ between groups. CONCLUSIONS: In this small, randomized study, inhaled
      steroids conferred no advantages to intravenous steroids in the management of
      ventilator-dependent preterm infants.

PMID- 11948382
TI  - Dexamethasone therapy and Candida sepsis in neonates less than 1250 grams.
AB  - OBJECTIVE: To determine whether dexamethasone use increases the risk for Candida
      sepsis (CS) in very low birth weight premature infants (<1250 g). DESIGN:
      Retrospective chart review of all infants with a birth weight <1250 g, admitted
      to the neonatal intensive care unit of the MetroHealth Medical Center, Cleveland,
      Ohio between January 1, 1996 and December 31, 1999. Infant groups with (n=65) and
      without (n=229) CS were compared. RESULTS: Two hundred and ninety four infants
      with a birth weight <1250 g were identified. CS was diagnosed at a median age of
      18 days, and 6 of 65 (10%) infants died directly from Candida-related
      complications. Candida albicans (n=30, 60%) and Candida parapsilosis (n=14, 25%)
      were the predominant isolates. Use of dexamethasone in infants at risk for
      chronic lung disease before 14 days of age (p=0.001), duration of antibiotics
      (p=0.001), and total duration of parenteral nutrition and intralipid (p=0.0001)
      were all significantly greater in infants who developed CS. Regression analysis
      showed that duration of antibiotics before the diagnosis of Candida infection
      (r(2)=0.69, p=0.0002) and duration of dexamethasone (r(2)=0.93, p=0.0002)
      correlated with Candida infection. Early dexamethasone use was also related to
      the age at diagnosis of Candida infection (r(2)=0.51, p=0.01). CONCLUSIONS:
      Dexamethasone therapy and prolonged duration of antibiotics are associated with
      Candida infection in premature infants.

PMID- 11948383
TI  - "Proactive" management of percutaneously inserted central catheters results in
      decreased incidence of infection in the ELBW population.
AB  - OBJECTIVE: Extremely low birth weight (ELBW) infants often acquire catheter
      related infections (CRIs) when a percutaneously inserted central catheter (PICC)
      is used for parenteral nutrition or drug administration. Our objective was to
      compare the incidence of CRIs after we established a "PICC Maintenance Team" for
      the proactive management--compared to expectant management--of these lines. STUDY
      DESIGN: We did a prospective collection and analysis of catheter-related sepsis
      data over a 15-month period from February 1, 1998 through May 1, 1999. Eligible
      patients included all neonates weighing <1000 g at birth. RESULTS: There was a
      significantly decreased incidence of CRIs, to a rate of 7.1%, or 5.1/1000
      catheter days (p<0.05). CONCLUSION: "Proactive" management of PICC, significantly
      reduced the incidence of CRIs. The reduction in infection rate is estimated to
      save 180 hospitalized patient days/100 very low birth weight neonates, with a
      concomitant savings in morbidity and medical expense.

PMID- 11948384
TI  - Pain during Mogen or PlastiBell circumcision.
AB  - Routine neonatal circumcision can be a painful procedure. Although analgesia for
      circumcision has been studied extensively, there are few studies comparing which
      surgical technique may be associated with the least pain and discomfort when
      carried out by pediatric trainees. OBJECTIVE: We studied two commonly used
      techniques for circumcision to determine which was associated with less pain and
      discomfort. STUDY DESIGN: In a randomized, prospective, but not blinded study,
      newborns were circumcised either by Mogen clamp or by PlastiBell. All received
      dorsal nerve blocks with lidocaine. Fifty-nine well, term, newborn infants at San
      Francisco General Hospital were studied from 1997 to 1998. Circumcisions were
      carried out mostly by interns and residents in family practice and pediatrics.
      Pain was assessed by measuring duration of the procedure and by a simple
      behavioral score done sequentially. RESULTS: Dorsal nerve blocks were judged to
      be fully effective in over 70% of cases. Neither Mogen nor PlastiBell was
      associated with greater pain per 3-minute time period, but the PlastiBell
      technique on average took nearly twice as long as the Mogen procedure (20 vs 12
      minutes). We judged that 60% of the infants had pain or discomfort associated
      with the procedure that was excessive. Residents and interns universally
      preferred the Mogen technique over the PlastiBell because of the former's
      simplicity. CONCLUSION: During the procedure, Mogen circumcision is associated
      with less pain and discomfort, takes less time, and is preferred by trainees when
      compared with the PlastiBell.

PMID- 11948385
TI  - Accuracy of a new low-flow sidestream capnography technology in newborns: a pilot
      study.
AB  - OBJECTIVE: To evaluate the accuracy of a new low-flow sidestream capnography
      technology and analyze components of the capnogram in mechanically ventilated
      newborns with and without pulmonary disease. METHODS: Twenty patients were
      prospectively identified. Eligible infants were mechanically ventilated and had
      an indwelling arterial catheter. Two groups were identified: newborns who were
      receiving mechanical ventilation for pulmonary diseases, and newborns who were
      receiving postoperative mechanical ventilation for nonpulmonary conditions. End
      tidal CO(2) (PetCO(2)) was measured for 1-minute pre- and post-arterial blood
      sampling, and PetCO(2) and PaCO(2) were compared for each patient. Eight
      quantitative waveform parameters were also measured on all patients. RESULTS:
      Newborns in the pulmonary group (n=13) (persistent pulmonary hypertension of the
      newborn/meconium aspiration syndrome, respiratory distress syndrome, pneumonia)
      and newborns in the control group (n=7) were matched for birth weight,
      gestational age, and postnatal age. PetCO(2)-PaCO2 Gradient values were higher in
      the pulmonary group (7.4+/-3.3 mm Hg) than controls (3.4+/-2.4 mm Hg). Four
      waveform parameters (ascending slope, alveolar angle, alpha angle, descending
      angle) were identified, which independently differentiated patients with
      pulmonary disease from controls. CONCLUSIONS: Low-flow capnography with
      Microstream technology accurately measured alveolar CO(2) in newborns without
      pulmonary disease, as demonstrated by normal PetCO(2)-PaCO(2) gradients. The
      measured PetCO(2)-PaCO(2) gradient, as expected, was significantly higher in
      newborns with pulmonary disease. We also identified four quantitative waveform
      parameters that may be useful in differentiating between mechanically ventilated
      newborn patients with and without lung disease.

PMID- 11948386
TI  - Effect of position changing on bilirubin levels during phototherapy.
AB  - OBJECTIVE: Turning of infants during phototherapy for hyperbilirubinemia is
      practiced in many nurseries. However, there is little research evidence in
      support of this practice. This study examined the effect of turning on serum
      total bilirubin concentration and on the duration of phototherapy. STUDY DESIGN:
      We first conducted a pilot study in term infants requiring phototherapy using
      transcutaneous bilirubinometry in order to determine the time required to clear
      the skin of bilirubin. This "blanching time" was found to be approximately 150
      minutes. We then conducted a randomized study comparing turning the baby during
      phototherapy with care in the supine position only. RESULTS: Thirty term infants
      were enrolled in the study (turned - 14; supine - 16). No differences were found
      between the groups in baseline data, such as birth weight, gestational age, age
      at start of phototherapy, or type of feeds. Infants in the supine group showed a
      significantly larger drop in serum total bilirubin concentration and required a
      shorter duration of phototherapy. CONCLUSION: We conclude that infants should be
      nursed supine during phototherapy. Based on these results, we propose a
      modification to the traditional model of bilirubin kinetics during phototherapy.

PMID- 11948389
TI  - The history of congenital diaphragmatic hernia from 1850s to the present.
AB  - Congenital diaphragmatic hernia (CDH) is believed to result from incomplete
      fusion of the pleuroperitoneal membrane, and passage of the abdominal contents
      into the chest. A historical review of the literature on this subject shows a
      wide divergence of opinion on the etiology of the various types of CDH, and on
      the recommended treatment. A variety of theories regarding its causes and the
      optimal way of approaching it have been published from the mid 19th century
      through the 20th century, and are reviewed in this article.

PMID- 11948388
TI  - Maternal floor infarction of the placenta: association with central nervous
      system injury and adverse neurodevelopmental outcome.
AB  - OBJECTIVE: To compare cranial ultrasound studies and neurodevelopmental outcome
      of preterm infants affected by maternal floor infarction (MFI) of the placenta to
      gestational age-matched controls over an 8-year period from a single institution.
      STUDY DESIGN: Retrospective case/control study. RESULTS: Compared to gestational
      age-matched controls, infants born to mothers with MFI had a higher incidence of
      CNS injury on neonatal cranial ultrasound examinations and at follow-up were more
      likely to have a suspicious or abnormal neurologic examination. MFI cases had
      lower developmental scores in all areas tested and were more likely to have
      neurodevelopmental impairment. CONCLUSION: Infants born to mothers with MFI
      should have serial neonatal cranial ultrasound examinations to detect CNS injury
      and neurodevelopmental assessment during early childhood.

PMID- 11948387
TI  - Racial differences in birth weight of term infants in a northern California
      population.
AB  - BACKGROUND: Census data show that an increasing proportion of the population of
      the United States is of Asian or Hispanic origin. Reference curves used to
      characterize fetal growth relative to gestational age are predominantly based on
      data for White infants. The goal of this study was to compare the birth weight
      distributions for term Asian or Hispanic infants with that for White infants, and
      to determine whether the prevalence of small (SGA) or large size(LGA) for
      gestational age differs between Asian or Hispanic and White infants. SETTING: A
      community hospital in Northern California. STUDY DESIGN: Data was collected
      prospectively from May 1 to September 13, 2000 on all singleton term infants born
      at this hospital. Gestational age was assessed by the best obstetrical estimate
      and ethnicity was determined by parental report. Infants were categorized as
      White, Hispanic, Chinese, Asian Indian, Other Asian, and Other. Birth weights,
      length, and head circumferences were compared using ANOVA and the Student-Newman
      Keuls test. Differences in rates of diagnosis of SGA or LGA were assessed by chi
      square. RESULTS: 1539 infants were included in the study sample; 30% were White,
      21% Asian Indian, 15% Chinese, 9% Hispanic, 7% other Asian, and 18% Other. Asian
      (Chinese, Asian Indian, or Other Asian), Hispanic, and Other babies had lower
      mean birth weights, shorter mean lengths, and smaller mean head circumferences
      than White babies. Asian, Hispanic, and Other male babies were lighter, shorter,
      and had smaller heads than white male babies. Asian females, but not Hispanic or
      Other ones, were lighter and had smaller head circumferences than White females;
      Asian Indian, Other Asian, and Other females had shorter lengths than White
      female infants. Indian and Other Asian, but not Chinese, babies were more likely
      than White babies to be SGA; babies in all three Asian groups were less likely
      than White babies to be LGA. CONCLUSION: Failure to account for ethnic
      differences in intrauterine growth may lead to inaccurate diagnosis of fetal
      growth abnormalities in infants of Asian ancestry.

PMID- 11948391
TI  - Idiopathic neonatal giant cell hepatitis presenting with acute hepatic failure on
      postnatal day one.
AB  - We report a term male infant presenting on postnatal day 1 with fulminant hepatic
      failure. Described congenital infection, metabolic disorders, and cardiovascular
      etiologies of acute neonatal liver failure were assessed and eliminated. A liver
      biopsy on postnatal day 10 showed neonatal giant cell hepatitis (NGCH) with an
      unusual degree of fibrosis for this early postnatal age. NGCH is a clinical
      diagnosis of cholestatic disorders of unknown etiology in the newborn, and, to
      our knowledge, has not been previously associated with immediate neonatal hepatic
      failure. The giant cell transformation is a common response to a variety of
      insults and only rarely occurs beyond the neonatal period. Most cases present
      with cholestatic jaundice and varying degrees of coagulopathy, and, many, as in
      this case, show progressive resolution.

PMID- 11948390
TI  - Efficacy of phenytoin against hyponatremic seizures due to SIADH after
      administration of anticancer drugs in a neonate.
AB  - A neonate with the syndrome of inappropriate secretion of antidiuretic hormone
      (SIADH) developed refractory hyponatremic seizures following administration of
      anticancer drugs. The seizures did not respond to diazepam, phenobarbital, or
      lidocaine, but resolved immediately with administration of phenytoin. The low
      water-excretion capacity in neonates should be taken into consideration when
      fluid loading is attempted, to avoid renal damage upon administration of drugs
      such as cisplatin that have a potential damaging effect on the kidney. Phenytoin
      could be the therapy of choice for SIADH and resulting seizures in the neonatal
      period.

PMID- 11948392
TI  - Premature infant with severe periventricular leukomalacia associated with a large
      placental chorioangioma: a case report.
AB  - We present the first reported case of severe periventricular leukomalacia
      associated with a large placental chorioangioma. We believe that the large
      chorioangioma near the point of umbilical cord insertion was not only disrupting
      fetoplacental circulation but may also have led to the periventricular
      leukomalacia lesions.

PMID- 11948393
TI  - Chronic granulomatous disease of childhood: neonatal serratia, hepatic abscesses,
      and pulmonary aspergillosis.

PMID- 11948395
TI  - Characterization of the p53-rescue drug CP-31398 in vitro and in living cells.
AB  - The Pfizer compound CP-31398 has been reported to stabilize the core domain of
      the tumour suppressor p53 in vitro and be an effective anti-cancer drug by virtue
      of rescuing destabilized mutants of p53. We did not detect any interaction
      between the p53 core domain and CP-31398 in vitro by a wide range of quantitative
      biophysical techniques over a wide range of conditions. CP-31398 did not
      stabilize p53 in our experiments. However, we found that CP-31398 intercalated
      with DNA and also altered and destabilized the DNA-p53 core domain complex. We
      analysed by NMR TROSY the interaction of the domain with a DNA oligomer and
      identified the changes in the complex on the binding of CP-31398. CP-31398 also
      decreased sequence-specific DNA binding of wild-type p53 and His-273 mutant p53.
      CP-31398 had a non-specific toxic effect independent of mutant p53 expression in
      several cell lines carrying Tet-regulated mutant p53. CP-31398 caused a small
      increase in MDM-2 expression and a more pronounced p53-independent increase in
      Bax expression. CP-31398 did, however, induce the PAb1620 epitope (characteristic
      of native p53) in cells expressing His-175 mutant p53. This was prevented by
      cycloheximide, suggesting that any stabilizing action of CP-31398 would have to
      be on newly synthesized p53. One of the unstable mutants that was reported to
      have been rescued by CP-31398, R249S, does not bind DNA when folded at lower
      temperatures.

PMID- 11948396
TI  - p53 and recombination intermediates: role of tetramerization at DNA junctions in
      complex formation and exonucleolytic degradation.
AB  - Heteroduplex joints represent intermediates of Rad51-dependent recombination
      processes, which are recognized by p53 with extremely high affinities, in a
      manner independent of the DNA sequence content. To determine the structural
      elements required for complex formation, we monitored DNA-binding by protection
      against restriction endonuclease cleavage. We show that wild-type (wt) p53
      interacts with heteroduplex joints in the proximity of the flexible junction.
      Association of p53 within this junction region was also observed with preformed
      Rad51-heteroduplex complexes, whereas SSB counteracted p53 binding. At a distance
      of 31 bp from the junction p53 established very few contacts with the
      heteroduplex, despite the presence of an A-G mismatch. Consistently, p53
      dependent exonucleolytic degradation decreased when we raised the distance
      between the junction and the heteroduplex terminus by 27 bp. Different from the
      cancer-related mutant p53(273H), which did not recognize the junction,
      tetramerization defective p53-1262 was protection competent but displayed reduced
      complex stability in gel shifts. Moreover, p53-1262 performed exonucleolytic
      activities towards ssDNA like wtp53, but reduced degradation of heteroduplex
      joints. These results suggest that during recombination wild-type p53, as a
      tetramer, stably binds to strand transfer regions, enabling the protein to
      exonucleolytically correct heteroduplex intermediates early after strand
      invasion.

PMID- 11948397
TI  - Ganciclovir-induced apoptosis in HSV-1 thymidine kinase expressing cells:
      critical role of DNA breaks, Bcl-2 decline and caspase-9 activation.
AB  - Although ganciclovir (GCV) is most often used in suicide anticancer gene therapy,
      the mechanism of GCV-induced cell killing and apoptosis is not fully understood.
      We analysed the mechanism of apoptosis triggered by GCV using a model system of
      CHO cells stably transfected with HSV-1 thymidine kinase (HSVtk). GCV-induced
      apoptosis is due to incorporation of the drug into DNA resulting in replication
      dependent formation of DNA double-strand breaks and, at later stages, S and G2/M
      arrest. GCV-provoked DNA instability was likely to be responsible for the
      observed initial decline in Bcl-2 level and caspase-9/-3 activation. Further
      decline in the Bcl-2 level was due to cleavage of the protein by caspase-9, as
      demonstrated by use of caspase inhibitors and transfection with trans-dominant
      negative caspase expression vectors. Bcl-2 cleavage resulted in the appearance of
      a pro-apoptotic 23 kDa Bcl-2 fragment and in excessive cytochrome c release,
      dephosphorylation of BAD, cleavage of PARP and finally DNA degradation. Since
      Fas/CD95 and caspase-8 were only slightly activated we conclude GCV-induced
      apoptosis to occur in this cell system mainly by activating the mitochondrial
      damage pathway. This process is independent of p53 for which the cells are
      mutated. Caspase-9 mediated cleavage of Bcl-2 accelerates the apoptotic process
      and may explain the high potential of GCV to induce apoptosis. Data are also
      discussed as to implications for HSVtk gene therapy utilizing GCV.

PMID- 11948399
TI  - Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage
      independent survival of immortalized human keratinocytes.
AB  - The human metastasis-associated gene (MTA1), a member of the nucleosome
      remodeling complex with histone deacetylase activity, is frequently overexpressed
      in biologically aggressive epithelial neoplasms. Here, we extend this observation
      to squamous carcinoma cells, which express high levels of MTA1 relative to normal
      or immortalized keratinocytes. To address functional aspects of MTA1 expression,
      we established variants of human immortalized keratinocytes (HaCaT cells) by
      expressing MTA1 cDNA in both the sense and antisense orientations. We demonstrate
      that (1) forced MTA1 expression enhances migration and invasion of immortalized
      keratinocytes; (2) MTA1 expression is necessary but not sufficient for cell
      survival in the anchorage independent state; (3) MTA1 contributes to expression
      of the anti-apoptotic Bcl-2 family member Bcl-x(L); (4) MTA1 expression in
      immortalized keratinocytes depends, in part, on activation of the epidermal
      growth factor receptor (EGFR). These results establish that, in keratinocytes,
      MTA1 expression contributes to several aspects of the metastatic phenotype
      including survival in the anchorage independent state, migration, and invasion.

PMID- 11948398
TI  - Protein kinase D complexes with C-Jun N-terminal kinase via activation loop
      phosphorylation and phosphorylates the C-Jun N-terminus.
AB  - Protein kinase D (PKD), a downstream effector of protein kinase C (PKC), is
      implicated in suppression of the c-Jun N-terminal kinase (JNK) signaling pathway,
      however, its mechanism of action is unclear. Transphosphorylation of the PKD
      activation loop at serines 744/748 by a PKC mediated signal transduction pathway
      enhances its catalytic activity. Here we show that PKD activation loop
      phosphorylation at serines 744/748 via PKC, or mutation of these serines to
      glutamic acid (PKD-S744/748E) also results in complex formation with JNK,
      indicating that suppression of JNK signaling by PKD involves a direct interaction
      with JNK. Because catalytically active PKD associates with JNK we determined
      whether it could phosphorylate the c-Jun N-terminus as a potential mechanism by
      which it suppresses c-Jun Ser 63 phosphorylation when it complexes with JNK.
      Purified human PKD and either wild-type PKD from phorbol 12, 13-dibutyrate (PDB)
      stimulated cells or unstimulated constitutively active PKD (PKD-S744/748E),
      phosphorylated the c-Jun N-terminus between amino acids 1-89 at sites distinct
      from those phosphorylated by JNK. These results demonstrate, for the first time,
      phosphorylation dependent association of PKD with another signaling molecule and
      reveal a potential mechanism by which PKD could modulate the ability of JNK to
      phosphorylate c-Jun by phosphorylating alternative sites in the c-Jun N-terminus
      when it is complexed with JNK.

PMID- 11948400
TI  - Activation of peroxisome proliferator-activated receptor-gamma stimulates the
      growth arrest and DNA-damage inducible 153 gene in non-small cell lung carcinoma
      cells.
AB  - Activation of peroxisome proliferator-activated receptor (PPAR)-gamma by the
      thiazolidinedione (TZD) class of antidiabetic drugs elicits growth inhibition in
      a variety of malignant tumors. We clarified the effects of TZDs on growth of
      human non-small cell lung carcinoma (NSCLC) cells that express endogenous PPAR
      gamma. Troglitazone and pioglitazone caused inhibition of cellular growth and
      induced apoptosis of NSCLC cells in a time- and dose-dependent manner.
      Subtraction cloning analysis identified that troglitazone stimulated expression
      of the growth arrest and DNA-damage inducible (GADD)153 gene, and the increased
      expression of GADD153 mRNA was also confirmed by an array analysis of the 160
      apoptosis-related genes. Western blot analysis revealed that troglitazone also
      increased GADD153 protein levels in a time-dependent manner. Troglitazone did not
      stimulate GADD153 mRNA levels in undifferentiated 3T3-L1 cells lacking PPAR-gamma
      expression, whereas its induction was clearly observed in differentiated
      adipocytes expressing PPAR-gamma. Activity of the GADD153 promoter occurred in a
      NSCLC cell line in transient transcription assays and was significantly
      stimulated by troglitazone, although binding of PPAR/retinoid X receptor
      heterodimer was not detected in the promoter region in gel retardation assays.
      Inhibition of GADD153 gene expression by an antisense phosphorothionate
      oligonucleotide attenuated the troglitazone-induced growth inhibition. These
      findings collectively indicated that activation of PPAR-gamma by TZDs could cause
      growth inhibition and apoptosis of NSCLC cells and that GADD153 might be a
      candidate factor implicated in these processes.

PMID- 11948401
TI  - AP-1 transrepressing retinoic acid does not deplete coactivators or AP-1 monomers
      but may target specific Jun or Fos containing dimers.
AB  - Retinoic acid (RA) inhibits tumor promotion in many models in vivo and in vitro,
      among them mouse epidermal JB6 cells. RA treatment suppresses 12-O
      tetradecanoylphorbol-13-acetate (TPA) induced AP-1 activity, an activity that is
      required for transformation of JB6 P+ cells. The molecular mechanism of AP-1
      transrepression by retinoids is unclear, especially as related to inhibition of
      transformation. Overexpression of AP-1 components did not rescue TPA induced AP-1
      activation nor did a GST pull down experiment implicate direct binding, thus
      rendering unlikely both a Jun/Fos-RA-RAR direct interaction and a Jun/Fos
      sequestration mechanism. Overexpression of p300, SRC-1 or pCAF did not abrogate
      AP-1 suppression by RA, thus arguing against coactivator competition.
      Overexpression of the corepressor silencing mediator for retinoic acid and
      thyroid hormone receptors (SMRT) suppressed AP-1 activity. However, SMRT but not
      RA inhibited cJun transactivation, suggesting SMRT does not mediate RA
      transrepression. RA treatment also did not block TPA induced ERK phosphorylation,
      Jun/Fos family protein expression except for cFos, or DNA binding of the AP-1
      complex. The transcriptional activities of full-length JunB and full-length Fra
      1, but not the transactivation domain fusions, were increased by TPA treatment
      and suppressed by RA. Since these full-length fusions have bzip domains, the
      results suggest that JunB and/or Fra-1-containing dimers may constitute one
      target of RA for transrepression of AP-1.

PMID- 11948402
TI  - Site-directed mutagenesis of cysteine to serine in the DNA binding region of Nrf2
      decreases its capacity to upregulate antioxidant response element-mediated
      expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene.
AB  - NF-E2 related factor 2 (Nrf2) is a CNC/b-zip protein that regulates antioxidant
      response element (ARE)-mediated expression, and antioxidant induction, of
      detoxifying enzyme genes, including NAD(P)H:quinone oxidoreductase1 (NQO1). A
      comparison of Nrf2 from different species, and with other b-zip proteins,
      revealed the presence of a highly conserved cysteine residue at position 506 in
      the DNA binding domain of Nrf2. Site-directed mutagenesis was used to mutate this
      cysteine to serine. Transfection/over expression experiments in human
      hepatoblastoma (Hep-G2) cells demonstrated that mutant Nrf2 (mNrf2), containing
      the C506S mutation, was significantly less efficient in activating ARE-mediated
      gene expression, and induction in response to tert-butyl hydroquinone (t-BHQ), as
      copmpared with wild-type Nrf2. N-ethyl malemide (NEM), a sulfhydryl cross-linker,
      inhibited Nrf2 but not mNrf2C506S-mediated expression of NQO1. This further
      implicated the cysteine at position 506 in Nrf2 regulation of ARE-mediated gene
      expression. Nuclear localization experiments revealed that C506S mutation did not
      affect the retention of Nrf2 by INrf2/Keap1 in the cytosol, or its release in
      response to antioxidants. However, band and supershift assays showed a
      significant reduction in the binding of mNrf2C506S to the NQO1 gene ARE as
      compared with wild-type Nrf2. Therefore, the C506S mutation in Nrf2 lowered its
      affinity for the ARE, leading to decreased expression, and antioxidant induction,
      of NQO1.

PMID- 11948403
TI  - Mitogenic synergy through multilevel convergence of hepatocyte growth factor and
      interleukin-4 signaling pathways.
AB  - Hepatocyte growth factor (HGF) regulates various physiological and developmental
      processes in concert with other growth factors, cytokines and hormones. We
      examined interactions between cell signaling events elicited by HGF and the
      cytokine interleukin (IL)-4, in the IL-3-dependent murine myeloid cell line 32D
      transfected with the human HGF receptor, c-Met. HGF was a potent mitogen in these
      cells, and prevented apoptosis in response to IL-3 withdrawal. IL-4 showed modest
      anti-apoptotic activity, but no significant mitogenic activity. IL-4
      synergistically enhanced HGF-stimulated DNA synthesis, whereas only additive
      prevention of apoptosis was observed. IL-4 did not enhance HGF-dependent tyrosine
      phosphorylation of c-Met or Shc. In contrast, HGF-stimulated activation of MAP
      kinases was enhanced by IL-4, suggesting that the IL-4 and HGF signaling pathways
      converge upstream of these events. Although phosphatidylinositol 3-kinase (PI3K)
      inhibitors diminished HGF-induced mitogenesis, anti-apoptosis, and MAP kinase
      activation, IL-4 enhanced HGF signaling persisted even in the presence of these
      inhibitors. IL-4 enhancement of HGF signaling was partially blocked in 32D/c-Met
      cells treated with inhibitors of MEK1 or c-Src kinases, completely blocked by
      expression of a catalytically inactive mutant of Janus kinase 3 (Jak3), and
      increased in 32D/c-Met cells overexpressing STAT6. Our results suggest that the
      IL-4 and HGF pathways converge at multiple levels, and that IL-4-dependent Jak3
      and STAT6 activities modulate signaling events independent of PI3K to enhance HGF
      dependent mitogenesis in myeloid cells, and possibly other common cellular
      targets.

PMID- 11948404
TI  - Cyclopentenone causes cell cycle arrest and represses cyclin D1 promoter activity
      in MCF-7 breast cancer cells.
AB  - Evidence indicates that overexpression of cyclin D1 is an important event in
      malignant transformation of breast cancer cells. Therefore, cyclin D1 is a
      potential target for mechanistically-based chemoprevention/treatment of breast
      cancer. Treatment of serum-stimulated quiescent MCF-7 breast cancer cells with
      cyclopentenone (2-cyclopenten-1-one) blocked progression through G1 and into S
      phase. Growth arrest of the cyclopentenone-treated cells in G1 was associated
      with changes in the levels of several proteins that control the cell cycle,
      including a dramatic decrease in cyclin D1 protein expression. Cyclopentenone
      also decreased the abundance of cyclin D1 mRNA and nuclear transcripts,
      indicating that it regulated cyclin D1 expression at the transcriptional level.
      Cyclopentenone selectively inhibited the activity of the cyclin D1 and cyclin A
      promoters but not the activity of several other control promoters. Deletion
      analysis indicated that the cyclopentenone response element was located in the
      cyclin D1 core promoter. Additional functional studies showed that a sequence
      within the core promoter (CycY, located downstream from the initiator element)
      played an important role in activation of the cyclin D1 promoter in MCF-7 cells.
      Electrophoretic mobility shift assays demonstrated specific binding of the
      transcription factor BTEB to the CycY site. The cyclopentenone response element
      did not correspond to the CycY site but rather mapped to the initiator element
      itself. The overall results suggest that cyclopentenone interferes with the
      transcription initiation complex that assembles over the cyclin D1 initiator
      element, leading to selective inhibition of cyclin D1 gene transcription.

PMID- 11948405
TI  - Transcription activation of FLRG and follistatin by activin A, through Smad
      proteins, participates in a negative feedback loop to modulate activin A
      function.
AB  - Signaling of TGFbeta family members such as activin is tightly regulated by
      soluble binding proteins. Follistatin binds to activin A with high affinity, and
      prevents activin binding to its own receptors, thereby blocking its signaling. We
      previously identified FLRG gene from a B-cell leukemia carrying a
      t(11;19)(q13;p13) translocation. We and others have already shown that FLRG,
      which is highly homologous to follistatin, may be involved in the regulation of
      the activin function through its binding to activin. In this study, we found
      that, like follistatin, FLRG protein inhibited activin A signaling as
      demonstrated by the use of a transcriptional reporter assay, and blocked the
      activin A-induced growth inhibition of HepG2 cells. We have recently shown that
      the TGFbeta-induced expression of FLRG occurs at a transcriptional level through
      the action of Smad proteins. Here we show that activin A increases FLRG and
      follistatin at both the mRNA and protein levels. We found that Smad proteins are
      involved in the activin A-induced transcription activation of FLRG and
      follistatin. Finally we demonstrate that FLRG protein regulates its own activin
      induced expression. In conclusion, activin A induces FLRG and follistatin
      expression. This observation, in conjunction with the antagonistic effect of FLRG
      and follistatin on activin signaling, indicates that these two proteins
      participate in a negative feedback loop which regulates the activin function.

PMID- 11948406
TI  - PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade
      activation of the ERK pathway.
AB  - The serine/threonine kinase Raf-1 acts downstream of Ras in the MAPK pathway
      leading to ERK activation in response to mitogens. Raf-1 has oncogenic potential,
      but is normally controlled by a complex interplay of inhibitory and activating
      mechanisms. Although Raf-1 is phosphorylated in unstimulated cells, mitogens
      cause its membrane recruitment by Ras and subsequent phosphorylation on
      additional sites. Some of these events modulate Raf-1 kinase activity while
      others determine interactions with other proteins. These changes regulate the
      ability of Raf-1 to phosphorylate its downstream targets MEK1 and MEK2. Rho
      family small G proteins act synergistically with Raf-1 to stimulate the ERK
      pathway by a cross-cascade mechanism that enhances MEK phosphorylation by Raf-1.
      Here we show that both Raf-1 and MEK1 are phosphorylated by PAK1 and that
      mutations at PAK1 phosphorylation sites in either protein prevent cross-cascade
      activation. In contrast, MEK1 activation by constitutively-active Raf-1 is
      refractory to mutations at PAK1 phosphorylation sites. Phosphorylation of MEK1 on
      serine 298 does not appear to regulate the interaction between Raf-1 and MEK1,
      but rather the ability of Raf-1 to phosphorylate MEK1 with which it is complexed
      in vivo. Our findings indicate that PAK1 primes MEK1 for activation by Raf-1 and
      imply another level of regulation in the ERK cascade.

PMID- 11948407
TI  - Complex roles of tissue inhibitors of metalloproteinases in cancer.
AB  - Matrix metalloproteinases (MMPs) is tightly associated with extracellular matrix
      (ECM) turnover, which plays a very active role in tumor invasion and metastasis.
      Tissue inhibitors of metalloproteinases (TIMPs) plays a critical role in the
      homeostasis of ECM by regulating the activity of MMPs. TIMPs are well-known for
      their ability to inhibit MMP activity thereby inhibiting tumor growth and
      metastasis. However, many evidences suggest that TIMPs are multifunctional
      proteins, which regulate cell proliferation, apoptosis, proMMP-2 activation, and
      angiogenesis. These effects may be through MMP-dependent or MMP-independent
      pathways. Recent data indicate that TIMPs have many paradoxical roles in
      tumorigenesis. In particular, both inhibitory effect and stimulatory effect on
      tumorigenesis have been demonstrated in many animal models in which TIMPs were
      overexpressed in cancer cells or in mice. Elevated TIMP levels are reported in
      association with cancer progression and identified as poor prognostic indicators
      in several human tumor types. Herein, we review the complex roles of TIMPs in
      cancer growth and metastasis.

PMID- 11948408
TI  - Acetyltransferase machinery conserved in p300/CBP-family proteins.
AB  - CREB-binding protein (CBP) and p300 are highly conserved and functionally related
      transcription coactivators and histone/protein acetyltransferases. They are tumor
      suppressors, participate in a wide variety of physiological events, and serve as
      integrators among different signal transduction pathways. In this study, 11
      distinct proteins that have a high degree of homology with the amino acid
      sequence of p300 have been identified in current protein databases. All of these
      11 proteins belong to either animal or plant multicellular organisms (higher
      eucaryotes). Conservation of p300/CBP domains among these proteins was examined
      further by sequence alignment and pattern search. The domains of p300/CBP that
      are required for the HAT function, including PHD, putative CoA-binding, and ZZ
      domains, are conserved in all of these 11 proteins. This observation is
      consistent with the previous functional assays and indicates that they are a
      family of acetyltransferases, i.e. p300/CBP acetyltransferases (PCAT). TAZ
      domains (TAZ1 and/or TAZ2) of PCAT proteins may allow them to participate in
      transcription regulation by either directly recruiting transcription factors,
      acetylating them subsequently, or directing targeted acetylation of nucleosomal
      histones.

PMID- 11948409
TI  - Positional cloning identifies a novel cyclophilin as a candidate amplified
      oncogene in 1q21.
AB  - Gains of 1q21-q23 have been associated with metastasis and chemotherapy response,
      particularly in bladder cancer, hepatocellular carcinomas and sarcomas. By
      positional cloning of amplified genes by yeast artificial chromosome-mediated
      cDNA capture using magnetic beads, we have identified three candidate genes
      (COAS1, -2 and -3) in the amplified region in sarcomas. COAS1 and -2 showed
      higher amplification levels than COAS3. Most notably, amplification was very
      common in osteosarcomas, where in particular COAS2 was highly expressed. COAS1
      has multiple repeats and shows no homology to previously described genes, whereas
      COAS2 is a novel member of the cyclosporin-binding peptidyl-prolyl isomerase
      family, very similar to cyclophilin A. COAS2 was overexpressed almost exclusively
      in aggressive metastatic or chemotherapy resistant tumours. Although COAS2 was
      generally more amplified than COAS1, it was not expressed in well-differentiated
      liposarcomas, where amplification of this region is very common. All three genes
      were found to be amplified and over-expressed also in breast carcinomas. The
      complex nature of the 1q21-23 amplicons and close proximity of the genes make
      unequivocal determination of the gene responsible difficult. Quite likely, the
      different genes may give selective advantages to different subsets of tumours.

PMID- 11948410
TI  - Discovery of differentially expressed genes in human breast cancer using
      subtracted cDNA libraries and cDNA microarrays.
AB  - Identifying novel and known genes that are differentially expressed in breast
      cancer has important implications in understanding the biology of breast
      tumorigenesis and developing new diagnostic and therapeutic agents. In this study
      we have combined two powerful technologies, PCR-based cDNA subtraction and cDNA
      microarray, as a high throughput methodology designed to identify cDNA clones
      that are breast tumor- and tissue-specific and are overexpressed in breast
      tumors. Approximately 2000 cDNA clones generated from the subtracted breast tumor
      library were arrayed on the microarray chips. The arrayed target cDNAs were then
      hybridized with 30 pairs of fluorescent-labeled cDNA probes generated from breast
      tumors and normal tissues to determine the tissue distribution and tumor
      specificity. cDNA clones showing overexpression in breast tumors by microarray
      were further analysed by DNA sequencing, GenBank and EST database searches, and
      quantitative real time PCR. We identified several known genes, including
      mammaglobin, cytokeratin 19, fibronectin, and hair-specific type II keratin,
      which have previously been shown to be overexpressed in breast tumors and may
      play an important role in the malignance of breast. We also discovered B726P
      which appears to be an isoform of NY-BR-1, a breast tissue-specific gene. Two
      additional clones discovered, B709P and GABA(A) receptor pi subunit, were not
      previously described for their overexpression profile in breast tumors. Thus,
      combining PCR-based cDNA subtraction and cDNA microarray allowed for an efficient
      way to identify and validate genes with elevated mRNA expression levels in breast
      cancer that may potentially be involved in breast cancer progression. These
      differentially expressed genes may be of potential utility as therapeutic and
      diagnostic targets for breast cancer.

PMID- 11948412
TI  - Inhibition of TRAIL-induced apoptosis by Bcl-2 overexpression.
AB  - Primary or acquired resistance to current treatment protocols remains a major
      concern in clinical oncology and may be caused by defects in apoptosis programs.
      Since recent data suggest that TRAIL can bypass apoptosis resistance caused by
      Bcl-2, we further investigated the role of Bcl-2 in TRAIL-induced apoptosis. Here
      we report that overexpression of Bcl-2 conferred protection against TRAIL in
      neuroblastoma, glioblastoma or breast carcinoma cell lines. Bcl-2 overexpression
      reduced TRAIL-induced cleavage of caspase-8 and Bid indicating that caspase-8 was
      activated upstream and also downstream of mitochondria in a feedback
      amplification loop. Importantly, Bcl-2 blocked cleavage of caspases-9, -7 and -3
      into active subunits and cleavage of the caspase substrates DFF45 or PARP. Also,
      Bcl-2 blocked cleavage of XIAP and overexpression of XIAP conferred resistance
      against TRAIL indicating that apoptosis was also amplified through a feedforward
      loop between caspases and XIAP. In contrast, in SKW lymphoblastoid cells, TRAIL
      induced activation of caspase-8 directly translated into full activation of
      caspases, cleavage of XIAP, DFF45 or PARP and apoptosis independent of Bcl-2
      overexpression, although Bcl-2 similarly inhibited loss of mitochondrial membrane
      potential and the release of cytochrome c, AIF and Smac from mitochondria in all
      cell types. By demonstrating a cell type dependent regulation of the TRAIL
      signaling pathway at different level, e.g. by Bcl-2 and by XIAP, these findings
      may have important clinical implication. Thus, strategies targeting the molecular
      basis of resistance towards TRAIL may be necessary in some tumors for cancer
      therapy with TRAIL.

PMID- 11948414
TI  - Hepatocyte growth factor/scatter factor activates the ETS1 transcription factor
      by a RAS-RAF-MEK-ERK signaling pathway.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) induces scattering and
      morphogenesis of epithelial cells through the activation of the MET tyrosine
      kinase receptor. Although the activated MET receptor recruits a number of
      signaling proteins, little is known of the downstream signaling pathways
      activated by HGF/SF. In this study, we wished to examine the signaling pathway
      leading to activation of the ETS1 transcription factor. Using in vitro and in
      vivo kinase assays, we found that HGF/SF activates the ERK1 MAP kinase, leading
      to the phosphorylation of the threonine 38 residue of ETS1 within a putative MAP
      kinase phosphorylation site (PLLT38P). This threonine residue was neither
      phosphorylated by JNK1, nor by p38 MAP kinases and was required for the induction
      of transcriptional activity of ETS1 by HGF/SF. Using kinase and transcription
      assays, we further demonstrated that phosphorylation and activation of ETS1
      occurs downstream of a RAS-RAF-MEK-ERK pathway. The functional involvement of
      this pathway in HGF/SF action was demonstrated using U0126, a pharmacological
      inhibitor of MEK, which blocked phosphorylation and activation of ETS1, RAS
      dependent transcriptional responses, cell scattering and morphogenesis. These
      data demonstrated that ETS1 is a downstream target of HGF/SF acting through a RAS
      RAF-MEK-ERK pathway and provides a signaling pathway leading to the regulation of
      gene expression by HGF/SF.

PMID- 11948413
TI  - IFNgamma sensitizes for apoptosis by upregulating caspase-8 expression through
      the Stat1 pathway.
AB  - Resistance of tumors to cytotoxic therapy may be due to disrupted apoptosis
      programs and remains a major obstacle in cancer treatment. Here, we report that
      IFNgamma sensitizes resistant tumor cells with absent or low caspase-8 expression
      for apoptosis induced by death-inducing ligands or cytotoxic drugs by
      upregulating caspase-8 through a Stat1/IRF1 dependent pathway. Combined treatment
      using IFNgamma with TRAIL, APO1, TNFalpha or cytotoxic drugs cooperated to
      trigger apoptosis in various resistant tumor cell lines derived from Ewing tumor,
      neuroblastoma or medulloblastoma, while single agents exerted only a minimal
      effect. Importantly, IFNgamma induced caspase-8 expression also in cells with
      inactivation of the caspase-8 gene by hypermethylation, although no direct effect
      of IFNgamma on the methylation status of regulatory sequences of the caspase-8
      gene was found. IFNgamma-mediated facilitation of apoptosis was inhibited by the
      caspase-8 specific inhibitor zIETD.fmk or in caspase-8 mutant Jurkat cells
      implying a prominent role of caspase-8 in mediating sensitization by IFNgamma.
      Upregulation of caspase-8 and sensitization for apoptosis by IFNgamma was blocked
      by overexpression of dominant-negative mutants of Stat1 or in Stat1-deficient U3A
      cells, while complementation of Stat1-deficient U3A cells with wild-type Stat1
      restored the IFNgamma effect. Moreover, ectopic expression of IRF1 induced
      caspase-8 expression thereby sensitizing cells for TRAIL-, APO1- or doxorubicin
      induced apoptosis. These findings provide evidence that the Stat1/IRF1 pathway is
      involved in induction of caspase-8 expression and apoptosis initiated by IFNgamma
      and indicate that IFNgamma might be an effective strategy to sensitize various
      resistant tumor cells with deficient caspase-8 expression for chemotherapy- or
      death receptor-induced apoptosis.

PMID- 11948415
TI  - Deregulated DNA polymerase beta strengthens ionizing radiation-induced
      nucleotidic and chromosomal instabilities.
AB  - DNA polymerase beta (Pol beta) is an error-prone enzyme which has been found to
      be overexpressed in several human tumors. By using a couple of recombinant CHO
      cells differing only from the exogenous expression of Pol beta, we showed here
      that cells overexpressing Pol beta are much more sensitive to IR treatments by
      increasing apoptosis. We also found that the surviving cells displayed an
      hypermutator phenotype which could be explained by different pathways involving
      Pol beta, such as (i) an increased capacity to incorporate into DNA the mutagenic
      dGTP analog, 8-oxo-dGTP, one of the most abundant purine-derived nucleotides
      exposed to gamma-irradiation, (ii) the induction of IR-induced DNA breaks and
      (iii) accumulation of chromosome aberrations induced by radiation. Alteration of
      Pol beta expression in irradiated cells thus appears to strengthen both cell
      death and genetic changes associated with a malignant phenotype. These data
      provide new insights into the cellular response to radiations and the associated
      carcinogenic consequences.

PMID- 11948416
TI  - Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung
      cancers.
AB  - The CHFR gene, which was recently cloned by Scolnick and Halazonetis in search
      for a novel mitotic checkpoint gene with fork-head association motifs, has been
      suggested to play a key role in the mitotic prophase checkpoint. In this study,
      we demonstrated tumor-specific aberrant hypermethylation of the promoter region
      of the CHFR gene in a significant fraction of lung cancers in association with
      loss of detectable levels of CHFR transcripts. Aberrant hypermethylation was
      observed in seven of 37 primary lung cancer cases. Treatment with the
      demethylating agent 5-aza-2'-deoxycytidine restored expression of the CHFR gene
      in lung cancer cell lines exhibiting aberrant hypermethylation and loss of its
      expression. In contrast, genetic alterations were found to be infrequent in lung
      cancers. This is the first description of aberrant hypermethylation of the CHFR
      gene in any type of human cancer, and provides further evidence of the
      involvement of multiple checkpoint alterations in lung cancer.

PMID- 11948417
TI  - Antiviral agent Cidofovir restores p53 function and enhances the radiosensitivity
      in HPV-associated cancers.
AB  - High-risk human papillomaviruses (HPVs) have been associated to the development
      of cervical and some other human cancers. Most of them express E6 and E7
      oncoproteins, able to bind to p53 and retinoblastoma (pRb) tumor suppressor
      proteins respectively and neutralize their function. Restoration of these
      pathways by blocking E6 and E7 expression would provide a selective therapeutic
      effect. Here, we show that a clinically approved antiviral agent Cidofovir
      reduced E6 and E7 expression in cervical carcinoma Me180 and head and neck
      squamous cell carcinoma HEP2 cells at the transcriptional level. Cidofovir
      induced the accumulation of active p53 and pRb associated to induction of cyclin
      dependent kinase inhibitor p21(WAF1/CIP1) in Me180 and HEP2 cells. p53 induction
      was also shown in Hela HPV-positive cervical carcinoma cell line. In addition, S
      phase cell cycle accumulation with concomitant decrease of cyclin A expression
      were associated to the antiproliferative activity of Cidofovir in HPV-treated
      cells. Combining Cidofovir to irradiation both in vivo and in nude mice
      xenografts resulted in a marked radiosensitization in HPV-positive cells, which
      was not observed in virus negative cells. This study provides the basis for a new
      anticancer strategy to enhance the antitumor effect of ionizing radiation in HPV
      related cancers, without increase deleterious effects.

PMID- 11948418
TI  - Src kinase contributes to the metastatic spread of carcinoma cells.
AB  - The involvement of Src kinase during carcinoma metastasis has been explored by
      using the NBT-II rat carcinoma cell line, which can be induced to scatter in
      vitro through Src activity. Here we show that Src activity was not required for
      growth of tumors derived from NBT-II cells injected into nude mice. In contrast,
      the presence of micrometastases was strictly dependent on Src, since the
      percentage of mice bearing metastases was dramatically reduced by the expression
      of a dominant-negative mutant of Src (SrcK-) or of Csk, the natural inhibitor of
      Src. Furthermore, metastatic cells originating from NBT-II cells displayed a Src
      activity higher than the parental cells, confirming that Src gives a selective
      advantage during the metastatic process. Finally, anatomopathological analysis of
      the primary tumors arising from NBT-II cells expressing Csk or SrcK- constructs
      revealed a highly differentiated epithelial phenotype contrasting with the poor
      differentiation of tumors derived from parental cells. The differentiated
      phenotype correlated with the presence of desmosomes at the cell periphery and
      the absence of vimentin intermediate filaments. Altogether, these data
      demonstrate that Src activity correlates with the loss of epithelial
      differentiation concomitantly with the increase of the metastatic potential of
      carcinoma cells.

PMID- 11948419
TI  - Motif analysis of the tumor suppressor gene MMAC/PTEN identifies tyrosines
      critical for tumor suppression and lipid phosphatase activity.
AB  - The tumor suppressor gene, MMAC/PTEN, has phosphatase, C2, and PDZ-binding
      domains as well as potential sites of regulation by phosphorylation, including
      tyrosine phosphorylation, which may contribute to its ability to modulate cell
      growth and viability. Several obvious and significant motifs were found in
      MMAC/PTEN, including most notably, a catalytic domain of tyrosine phosphatase
      (IHCxxGxxRS/T) and several potential tyrosine phosphorylation sites. To examine
      the functional significance of tyrosine phosphorylation of MMAC/PTEN, retroviral
      constructs were generated with mutations at two putative tyrosine phosphorylation
      sites (Y240A/Y240F and Y315A/Y315F). Stable expression of wild-type MMAC/PTEN in
      U251 human glioma cells (which do not normally produce a functional MMAC/PTEN
      gene product) resulted in a significant reduction of tumor growth in nude mice,
      decreased growth rate, saturation density, and colony formation in vitro, as well
      as dephosphorylation of D3-phosphorylated phosphatidylinositols (PtdIns) in
      vitro. Mutation of Y240 or Y315 to either alanine or phenylalanine abrogated the
      ability of MMAC/PTEN to alter growth rate, saturation density, and colony
      formation in vitro. The ability of MMAC/PTEN to limit tumor growth in nude mice
      was markedly decreased but not abrogated by mutation of Y240 or Y315 to alanine.
      Thus, Y240 and Y315 are required for MMAC/PTEN to decrease tumor growth in vitro
      and in vivo. In contrast to wild-type MMAC/PTEN, mutant MMAC/PTEN containing
      Y240A or Y315A was unable to dephosphorylate D3-phosphorylated PtdIns in vitro.
      Thus, Y240A and Y315A are involved in the ability of MMAC/PTEN to dephosphorylate
      PtdIns and regulate tumor cell growth in vitro and in vivo.

PMID- 11948420
TI  - Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF
      7 human breast cancer cells.
AB  - Caveolin-1 is an essential structural constituent of caveolae that has been
      implicated in mitogenic signaling and oncogenesis. Caveolin-1 is down-regulated
      in oncogene-transformed and tumor-derived cells. Antisense suppression of
      caveolin-1 or expression of a dominant negative form are sufficient for inducing
      cellular transformation. Expression of recombinant caveolin-1 inhibits anchorage
      independent growth in cancer cells. The present study was designed to determine
      whether this is caused by inhibition of cancer cell survival or cell
      proliferation, and to test if another important property of cancer cells, i.e.
      matrix invasion, is modulated by expression of caveolin. Utilizing MCF-7 human
      breast adenocarcinoma cells stably transfected with caveolin-1 (MCF-7/Cav1), we
      demonstrate that caveolin-1 expression decreases MCF-7 cell proliferation rate
      and markedly reduces their capacity to form colonies in soft agar. The loss of
      anchorage-independent growth is not associated with stimulation of anoikis; in
      fact, MCF-7/Cav1 cells exhibit increased survival after detachment as compared
      with MCF-7 cells, indicating that in these cells caveolin-1 inhibits anoikis.
      Analysis of matrix metalloprotease release and matrix invasion revealed that
      expression of caveolin-1 inhibits also these important metastasis-related
      phenomena. Plating MCF-7 cells on a laminin matrix resulted in activation of
      ERK1/2, which was dramatically inhibited in MCF-7/Cav1 cells. We conclude that
      high expression level of caveolin-1 in human breast cancer cells exerts a
      negative modulatory effect on anchorage-independent growth by inhibiting cell
      proliferation even though matrix-independent cell survival is enhanced. Caveolin
      1 expression inhibits also matrix invasion and blocks laminin-dependent
      activation of ERK1/2. The inhibitory effect of caveolin-1 on these transformation
      dependent processes supports the hypothesis that caveolin-1 acts as a tumor
      suppressor protein which may impose major phenotypic changes when expressed in
      human cancer cells.

PMID- 11948421
TI  - The mdm2 proto-oncogene sensitizes human medullary thyroid carcinoma cells to
      ionizing radiation.
AB  - We have analysed the radiation response of a human medullary thyroid carcinoma
      cell line (MTT), characterized by the absence of a functional p53 protein, and
      the consequences of MDM2 overexpression in this process. We show that the product
      of the mdm2 proto-oncogene is able to sensitize MTT cells to ionizing radiation.
      After radiation treatment, MTT cells display histograms consistent with a G2M
      arrest. MTT cells expressing MDM2 (MTT-mdm2) are unable to respond to DNA damage
      with G2M arrest, and display a high percentage of apoptosis. MTT-mdm2 cells show
      high levels of E2F-1 protein, suggesting that the induction of apoptosis observed
      upon MDM2 overexpression could be dependent on E2F-1. This observation is further
      supported with assays showing that E2F-1 binding to specific DNA sequences is
      enhanced in MTT-mdm2 cells. Likewise, transactivation of reporter constructs
      exclusively dependent on E2F-1 is also elevated after transfection with MDM2.
      This effect can be reverted by transient transfection with p19ARF. To link the
      expression of E2F-1 with the induction of apoptosis, we generated clonal cell
      lines overexpressing E2F-1. Transfection with E2F-1 results in a low number of
      outgrowing colonies with reduced proliferation rates, indicating that E2F-1 is
      deleterious for cell growth. This negative regulation correlates with an increase
      in the percentage of the cell population with DNA content below 2N, suggesting
      that E2F-1 promotes apoptosis. Finally, overexpression of E2F-1 sensitizes MTT
      cells to radiation exposure. We conclude that the effects observed by MDM2
      overexpression could be mediated by E2F-1.

PMID- 11948422
TI  - Differential effects of stress stimuli on a JNK-inactivating phosphatase.
AB  - Stress signals elicit a wide variety of cellular responses, many of which
      converge on the phosphorylation of JNK and p38 kinases, the activation of which
      has been well-characterized. How these kinases are switched off by
      dephosphorylation is not well understood. Here we describe how diverse cellular
      stresses affect differently the stability and activity of a JNK-inactivating dual
      specificity threonine-tyrosine phosphatase M3/6. Both anisomycin and arsenite
      activate the JNK pathway and, in addition, inactivate the M3/6 phosphatase.
      However, while anisomycin treatment of cells leads to M3/6 protein degradation,
      arsenite appears to inactivate M3/6 directly. These results might have
      implications for the mechanism of tumour promotion by arsenic.

PMID- 11948423
TI  - Molecular follow-up of preneoplastic lesions in bronchial epithelium of former
      Chernobyl clean-up workers.
AB  - Ionizing radiation is a potent lung carcinogen, but the precise molecular damage
      associated with it is still unknown. In this study we investigated cancer-related
      molecular abnormalities including K-ras (codon 12) mutation, p16(INK4A) promoter
      hypermethylation and microsatellite alterations at seven chromosomal regions in
      successive biopsies obtained from former Chernobyl cleanup workers in comparison
      with smokers and nonsmokers who have never had radiation exposure. Our results
      indicate that prolonged persistence of inhaled radioactive particles is
      associated with appearance of allelic loss at 3p12, 3p14.2 (FHIT), 3p21, 3p22-24
      (hMLH1) and 9p21 (p16INK4A) in bronchial epithelium of former Chernobyl clean-up
      workers. The prevalence of 3p14.2 allelic loss was associated with decreased
      expression of the FHIT mRNA in their bronchial epithelium in comparison with
      control group of smokers. During several years of our monitoring samples of
      epithelium were collected from the same area of bronchial tree. In epithelium
      exposed to carcinogens (tobacco smoke and/or radioactivity) the total number of
      molecular abnormalities was significantly higher in dysplasia and in
      morphologically normal foci progressed later to dysplasia than in these samples
      which never showed evidence of such progression. Our findings indicate that
      extensive cancer-related molecular abnormalities sequentially occur in radiation
      damaged bronchial epithelium of former Chernobyl clean-up workers.

PMID- 11948424
TI  - Overexpressed thioredoxin compensates Fanconi anemia related chromosomal
      instability.
AB  - The cause of the molecular defect of Fanconi anemia (FA) remains unknown. Cells
      from patients with FA exert an elevated spontaneous chromosomal instability which
      is further triggered by mitomycin C. The induced lability is reduced by
      overexpression of thioredoxin which is not the case for spontaneous instability.
      However, both are eliminated by overexpression of thioredoxin cDNA with an added
      nuclear localization signal. This implies that thioredoxin is lacking in the
      nuclei of FA cells. The total thioredoxin content in all FA cells tested is
      reduced. The resultant lack of nuclear thioredoxin can be the explanation for the
      major symptomatology in FA. Since thioredoxin is known to be the reactive
      cofactor of ribonucleotid reductase its shortcoming reduces the supply of
      deoxyribonucleotides thus hindering the DNA and replication repair with resultant
      chromosomal breaks. Furthermore, depression of tyrosine hydroxylase, the key
      enzyme of melanine synthesis, could be the basis for the pathognomotic 'cafe au
      lait' spots of FA. The observation of thioredoxin reduction in FA cells permits
      insight into the molecular phathophysiology of FA.

PMID- 11948425
TI  - Overexpression of mouse Mdm2 induces developmental phenotypes in Drosophila.
AB  - The Mdm2 proto-oncogene is amplified and over-expressed in a variety of tumors.
      One of the major functions of Mdm2 described to date is its ability to modulate
      the levels and activity of the tumor suppressor protein p53. Mdm2 binds to the N
      terminus of p53 and, through its action as an E3 ubiquitin ligase, targets p53
      for rapid proteasomal degradation. Mdm2 can also bind to other cellular proteins
      such as hNumb, E2F1, Rb and Akt; however, the biological significance of these
      interactions is less clear. To gain insight into the function of Mdm2 in vivo, we
      have generated a transgenic Drosophila strain bearing the mouse Mdm2 gene.
      Ectopic expression of Mdm2, using the UAS/GAL4 system, causes eye and wing
      phenotypes in the fly. Analysis of wing imaginal discs from third instar larvae
      showed that expression of Mdm2 induces apoptosis. Crosses did not reveal genetic
      interactions between Mdm2 and the Drosophila homolog of E2F, Numb and Akt. These
      transgenic flies may provide a unique experimental model for exploring the
      molecular interactions of Mdm2 in a developmental context.

PMID- 11948426
TI  - Frequent and histological type-specific inactivation of 14-3-3sigma in human lung
      cancers.
AB  - One isoform of the 14-3-3 family, 14-3-3sigma, plays a crucial role in the G2
      checkpoint by sequestering Cdc2-cyclinB1 in the cytoplasm, and the expression of
      14-3-3sigma is frequently lost in breast cancers. This loss of expression is
      thought to cause a G2 checkpoint defect, resulting in chromosomal aberrations.
      Since lung cancers frequently carry numerous chromosomal aberrations, we examined
      the DNA methylation status and expression level of the 14-3-3sigma gene in 37
      lung cancer cell lines and 30 primary lung tumor specimens. We found that small
      cell lung cancer (SCLC) cell lines frequently showed DNA hypermethylation (9 of
      13 lines, 69%), and subsequent silencing of the 14-3-3sigma gene. Among non-small
      cell lung cancers (NSCLC), large cell lung cancer cell lines showed frequent
      hypermethylation and silencing of 14-3-3sigma (4 or 7 lines, 57%). In contrast,
      in other NSCLC cell lines, hypermethylation occurred very rarely (1 of 17 lines,
      6%). All eight primary SCLC specimens examined also showed a loss or significant
      reduction in 14-3-3sigma expression in vivo, while a loss or reduction of 14-3
      3sigma expression was very rare in primary NSCLC specimens (1 of 22 tissues, 5%).
      This is the first description that indicates lung cancers frequently show
      significant inactivation of the 14-3-3sigma gene mainly due to DNA
      hypermethylation in SCLC, but rarely in NSCLC, suggesting involvement of the 14-3
      3sigma gene in lung tumorigenesis in a histological type-specific manner.

PMID- 11948427
TI  - SmgGDS displays differential binding and exchange activity towards different Ras
      isoforms.
AB  - Ras family GTPases play central roles in a wide variety of biological responses,
      including cell proliferation, differentiation, and oncogenic transformation. We
      searched for novel guanine nucleotide exchange factors of HRas and isolated small
      G-protein dissociation stimulator (smgGDS), a guanine nucleotide exchange factor
      known to act on numerous Ras and Rho family GTPases. SmgGDS specifically
      interacts with both dominant negative and nucleotide free forms of H and NRas,
      but not with the corresponding oncogenic forms. An effector domain mutant of
      HRas, HRasN17G37, selectively lost the ability to bind smgGDS. However, smgGDS
      does not catalyze guanine nucleotide exchange on either H or NRas in vitro. In
      contrast, substrates of smgGDS, such as KRas, Rac1, and RhoA, bind to smgGDS in
      both active and inactive forms which requires the presence of poly-basic residues
      in the C-termini of the GTPases. Our data suggest that the C-terminal poly-basic
      region of small GTPases is important for both binding and nucleotide exchange by
      smgGDS. Furthermore, these data underscore the idea that mammalian Ras isoforms
      are not functionally equivalent.

PMID- 11948428
TI  - Gene expression profile in fibroblast growth factor 2-transformed endothelial
      cells.
AB  - Fibroblast growth factor-2 (FGF2) exerts paracrine and autocrine functions on
      endothelial cells. FGF2-overexpressing murine aortic endothelial cells (FGF2-T
      MAE cells) induce opportunistic hemangioendothelioma-like tumors when inoculated
      in immunodeficient mice. To evaluate the impact of FGF2-mediated activation on
      gene expression profile in transformed endothelial cells, we performed
      subtractive suppression hybridization analysis between FGF2-T-MAE cells and
      parental MAE cells. The two cell populations were compared for differential gene
      expression also by gene macroarray hybridization with 32P-labeled cDNAs. The two
      approaches allowed the identification of 27 transcripts whose expression was
      upregulated by FGF2 in endothelial cells. With the exception of one unknown gene,
      the differentially expressed transcripts encoded for proteins involved in the
      modulation of cell cycle, differentiation, and cell adhesion. Among them, the
      stress-inducible genes A170, GADD45 and GADD153 are upregulated by FGF2
      transfection or recombinant growth factor treatment. Their expression was also
      induced in vascular tumors originated by parental or FGF2-transfected MAE cells
      in nude mice. This study extends the number of genes involved in tumor
      angiogenesis and/or endothelial cell transformation, a finding with possible
      implications for the discovery of novel targets for angiostatic therapy.

PMID- 11948429
TI  - Differential effects of JNK1 and JNK2 on signal specific induction of apoptosis.
AB  - The c-Jun N-terminal kinases (JNKs) are activated by a variety of stress inducing
      agents and are thought to regulate apoptosis in a cell type and signal-specific
      manner. We have used fibroblasts lacking JNK1 or JNK2 to define their roles in
      response to different stress signals. Lack of JNK1 results in reduced c-Jun
      phosphorylation and resistance to UV-induced cell death. JNK2 deficient cells
      show increased sensitivity to UV irradiation which correlates with elevated and
      sustained phosphorylation of JNK1 and c-Jun. On the contrary, both Jnk1-/- and
      Jnk2-/- cells were more sensitive to tumor necrosis factor - alpha (TNF-alpha)
      and sorbitol-induced cell death. Treatment of Jnk1-/- cells with these reagents
      resulted in reduced JNK activity and a concomitant reduction of c-Jun
      phosphorylation, suggesting that phosphorylation of c-Jun does not influence TNF
      alpha and sorbitol-induced apoptosis in fibroblasts. Moreover, both JNK1 and JNK2
      appear to negatively regulate apoptosis independent of c-Jun phosphorylation.
      These data provide genetic evidence that although the JNK pathway is activated by
      a plethora of signals, it is required only for the induction of UV-induced cell
      death in a c-Jun phosphorylation-dependent manner, but not for TNF-alpha and
      sorbitol-induced apoptosis.

PMID- 11948430
TI  - [Aggressiveness in schizophrenia: prevalence, psychopathological and
      sociodemographic correlates].
AB  - In a retrospective study we evaluated the patient files of all schizophrenic
      patients (ICD-criteria) admitted to the psychiatric hospital of the university of
      Munich between 1990 - 1995 (N = 2093). Relevant sociodemographic, clinical and
      psychopathological data as assessed by means of the AMDP protocol were studied.
      292 (14 %) of patients fullfilled the criterion aggression on admission. While
      there were few differences concerning many sociodemographic variables including,
      male schizophrenics were rated significantly more often to be aggressive than
      female schizophrenics. With respect to schizophrenic subtype disorganized
      patients were most likely to be aggressive. Psychopathological symptoms
      significantly associated with aggression were e.p. delusional ideas and
      disorganized thinking. Possible risk factors for aggression in schizophrenia and
      clinical implications are discussed.

PMID- 11948431
TI  - [Influence of the drug package information paper on compliance of neurological
      and psychiatric outpatients].
AB  - The influence of demographic parameter, the number of different drugs or the
      frequency of the single doses on the reliability of compliance was subject in
      different studies. The goal of this investigation was to examine the influence of
      the drug package information paper on the compliance of neurological-psychiatric
      patients. 951 patients of one quarter of a neurological-psychiatric practice were
      given a questionnaire, which examined the income behavior and the estimate of the
      meaning of the drug package information paper. 352 patients answered the
      questionnaires. Only 15.6 % refused it to answer the questionnaire. The remaining
      were not able to answer because of different reasons (dementia, aphasia, acute
      psychiatric disorders, foreign language origin, immobility, etc.). 98.1 %
      considered the drug package information paper to be important. Older patients and
      patients with lower education degree judged the drug package information paper to
      be too extensive. Only few patients (11.5 %) let the physician explain the drug
      package information paper. 86.3 % of the patients assumed the medication
      prescribed by the physician to be correct. 58.1 % of the patients however were
      not satisfied with the information by the physician. Patients with neuroses were
      particularly dissatisfied over the clearing-up by the physician (77.3 %). 73.3 %
      of the patients were deterred from taking in their medicines occasionally or
      frequently by the side effects described in the drug package information paper.
      59.9 % of the patients would take the medicine, if the physician insisted on it.
      Independently of the influence of the drug package information paper 57.5 % of
      the patients forgot to take their medicines occasionally or frequently. Patients
      with epilepsies and M. Parkinson were most compliant. In summary the
      investigation showed that the clearing-up only by the drug package information
      paper in contrast to the clearing-up by the physician leads to more non
      compliance.

PMID- 11948432
TI  - [Psychosocial Risk Factors of the Wish to be Dead in the Elderly].
AB  - BACKGROUND: Suicidal ideation is a common phenomenon in the elderly. The purpose
      of this report is to reveal the influence of psychosocial risk factors and
      psychiatric disorders on the wish to die in the elderly. METHOD: We compared the
      data of 54 persons (age 70+) who said that they wished to die with 462 persons
      without death wishes according to several psychosocial risk factors, physical
      health and psychiatric diagnoses. The data come from the Berlin Aging Study, an
      interdisciplinary assessment of an epidemiological random sample of 516 citizens
      in Germany. RESULTS: Using a MANOVA and logistic regression analysis the data
      indicated that the wish to be dead, even in these very old persons, was mostly
      associated with the occurrence of a major depression, self rated higher
      depressivity, higher age, female gender, and negative life conditions such as
      living in a nursing home. CONCLUSION: The results of this study support that the
      wish to be dead in the very old is very likely to be associated with the
      occurrence of a psychiatric disorder, especially major depression and the higher
      probability of negative life conditions. Thus, we emphasize the requirement of
      psychiatric assessment as well as treatment of those older people who want to
      die.

PMID- 11948433
TI  - [Reasons for Hospital Treatment of Psychiatric Patients before and after the
      Opening of a Satellite Ward].
AB  - A satellite ward is a psychiatric ward at a general hospital settled within the
      catchment area that is administered by a psychiatric hospital. The objective of
      the satellite model is to approach community treatment on the one hand and
      somatic medicine on the other hand, consequently diminishing the threshold for
      hospital treatment. This study investigated whether the diagnostic,
      psychopathologic and social reasons for admissions changed from this catchment
      area due to the lower threshold of a satellite ward. The results were controlled
      with another catchment area's admissions to the 30 km distant psychiatric
      hospital. The opening of the satellite ward was followed by an 81 % increase of
      admissions. In particular, admissions of patients with neuroses and personality
      disorders were more frequent. There was no change of the severity code of
      psychopathology at admission. From the catchment area of the satellite ward less
      patients were admitted involuntarily whereas more admissions happened due to
      social reasons and after patients' own decision.

PMID- 11948434
TI  - [Eugen Bleulers propositions to psychiatric treatment].
AB  - The historical review of Eugen Bleulers concepts and proposals to treatment in
      psychiatry, generally and especially for schizophrenia, covers the years between
      his inaugural lecture 1898 as professor of psychiatry at the University of Zurich
      to his last edition of his textbook 1937. Already at the beginning of his career
      as professor in Zurich, he had a very intimate knowledge of psychiatric patients
      from his 12 years as director of the Mental Hospital Rheinau (near Zurich) where
      he lived as a bachelor with his patients in the same building. In his inaugural
      lecture, Bleuler already discussed very practical problems of psychiatric
      service. e.g. work, employment, marriage, situation in patient's family, housing,
      occupational therapy etc. Working in the group of other patients should help to
      re-establish the relationship to the common reality and the society.
      Psychotherapy for schizophrenics was mentioned in 1911 as the only serious
      therapy, but was not further elaborated. In 1939, Bleuler was much more sceptical
      concerning the realistic possibilities of an efficient psychotherapy of
      schizophrenia. Psychoanalysis would only allow a psychological understanding of
      some symptoms in schizophrenia but would be unable to contribute to a theory of
      the underlying pathogenesis. In his view, schizophrenia has its own inherent
      development. This resignation concerning constructive and efficient therapy
      dominates his confession even in his last lecture when retiring 1927. Considering
      the paucity of therapeutic possibilities, Bleuler underlined the importance of
      prophylactic eugenic strategies.

PMID- 11948435
TI  - [Alfred Hauptmann - the fate of a german neurologist of jewish origin].
AB  - The pathway through life of the German psychiatrist and neurologist Alfred
      Hauptmann (1881 - 1948) and his work is described. It is exemplary for so many of
      his contemporaries of Jewish origin, who were forced to emigrate under the
      National Socialist dictatorship. Hauptmann's career was most of all marked by the
      short, but to him formative time with Max Nonne. Throughout his life his research
      focused on neurological topics. In 1926, Hauptmann got the chair of psychiatry at
      Halle University in order to continue the important neurological tradition of
      Eduard Hitzig, Carl Wernicke and Gabriel Anton. Until 1935, he worked as the
      director of the psychiatric clinic in Halle, but in the course of the
      Reichsburgergesetz he had to give up his chair and his work as a doctor. The way
      into emigration, which was accelerated by the temporary imprisonment in the
      concentration camp Dachau, is described considering personal documents. After his
      emigration into the United States, Hauptmann was not too successful in starting
      new as a scientist. His most important contribution is still the article on the
      efficacy of Phenobarbital as an antiepileptic, which had been written already in
      1912. For this reason, the Alfred-Hauptmann-Award for epilepsy research is
      awarded. In 1941 - after his emigration - he and Siegfried Joseph Thannhauser
      described the autosomal dominantly transmitted myopathy for the first time, which
      is today described as Hauptmann-Thannhauser myodystrophy. The name of Alfred
      Hauptmann should be unforgettable not only because of the entrance into medical
      nomenclature, but it should also remind of the man Alfred Hauptmann, standing for
      all those whose similar fates are still unknown until now.

PMID- 11948436
TI  - [Augmentation of selective serotonin reuptake inhibitors (SSRI) with atypical
      antipsychotics in the treatment of depression].
AB  - The treatment of severe depression represents a difficult task in the daily
      psychiatric practice. In certain cases, augmentation therapies in order to
      improve the efficacy of SSRIs can be useful. Recently, it has become possible to
      use atypical antipsychotics for SSRI augmentation. This option adds to the
      existing strategies in the treatment of depression and primary systematic studies
      show encouraging results. In this review, the possibility of a SSRI augmentation
      by additionally administering risperidone or olanzapine is critically discussed.

PMID- 11948437
TI  - Homologs of 1,2,5-hexahydro-3-one-1H-1,4-diazepine (DAP) as novel
      dipeptidomimetics and molecular scaffolds: efficient preparation of synthons.
AB  - Structurally constraint dipeptidomimetics represent an important class of
      conformationally rigid dipeptide surrogates and molecular scaffolds, which are
      frequently employed in peptide-based structure-activity relationships (SAR) and
      construction of combinatorial libraries. We report on the design of an improved
      and general synthetic procedure to prepare synthons related to the trisubstituted
      1,2,5-hexahydro-3-one-1H-1,4-diazepines [DAP(Xxx)(alpha7)] (DAP: 1,2,5-hexahydro
      3-one-1H-1,4-diazepine; DAP(Xxx)(alpha7): the homologous series of DAP in which
      alpha refers to the location of the chiral carbon in the i(th) amino acid, Xxx
      represents the three letter notation for the i-1 amino acids, and 7 denotes the
      number of atoms in the ring) and their higher homologs [DAP(Xxx)(alphaN)] [Xxx =
      Phe, Asp(beta-OcHex) (cHex: cyclohexyl), and Arg(N(G)-Tos] (Tos: p
      toluenesulfonyl); N = 8-10]. These dipetidomimetic structures are generated by
      reductive alkylation-mediated Calpha(i)-to-N(i-1) bridging between a Calpha (i)
      (CH(2))(i-1)(n)-COSEt (n = 1-4) and H(2)N-C(i-1)HR-CO(2)Fm (Fm: 9
      fluorenylmethyl) followed by H(2)N(i)-to-C(i-1)-CO(2)H lactam formation. We also
      describe the preparation of blocked N-Ac-[DAP(Phe)(alphaN)]-CONMe(2) (N = 8-10),
      which serve as model systems for detailed conformational analysis reported in the
      accompanying article.

PMID- 11948438
TI  - Structural characterization of a cyclic dipeptidomimetic: the effect of ring size
      on a 1,2,5-trisubstituted-3-oxo-1,4-diazepine system.
AB  - A series of dipeptidomimetics derived from C(alpha)(i)-to-N(i-1) side chain-to
      backbone amide cyclization of adjacent amino acids are structurally
      characterized. The resulting ring systems are either 1,2,5-trisubstituted-3-oxo
      1,4-diazepine (DAP) structurally related to benzodiazepines, commonly used in
      drug candidates and therapeutic agents, or higher homologs of it. Here, we
      examine the structural consequences of enlarging the ring size from seven members
      to eight-, nine-, and ten-membered rings. The structural features determined by
      high-resolution NMR methods, relying largely on homo- and heteronuclear coupling
      constants, indicate that variation of the ring leads to alternative conformations
      and topological orientations of the attached chemical moieties or functional
      groups. Controlling the topological display of the ring substituents required for
      biological action, using a molecular scaffold made up entirely of functional
      groups found in peptides, should facilitate the rational, stepwise transformation
      of peptide lead candidate into a nonpeptidic drug candidate.

PMID- 11948439
TI  - A study of conformational stability of poly(L-alanine), poly(L-valine), and
      poly(L-alanine)/poly(L-valine) blends in the solid state by (13)C cross
      polarization/magic angle spinning NMR.
AB  - 13C cross-polarization/magic angle spinning (CP/MAS) NMR and (1)H T(1rho)
      experiments of poly(L-alanine) (PLA), poly(L-valine) (PLV), and PLA/PLV blends
      have been carried out in order to elucidate the conformational stability of the
      polypeptides in the solid state. These were prepared by adding a trifluoroacetic
      acid (TFA) solution of the polymer with a 2.0 wt/wt % of sulfuric acid
      (H(2)SO(4)) to alkaline water. From these experimental results, it is clarified
      that the conformations of PLA and PLV in their blends are strongly influenced by
      intermolecular hydrogen-bonding interactions that cause their miscibility at the
      molecular level.

PMID- 11948440
TI  - Studies of low molecular weight samples of glucuronans with various acetylation
      degree.
AB  - Partially acetylated, high molecular weight glucuronans were produced by a
      Sinorhizobium meliloti mutant strain. Two native glucuronan samples with various
      degrees of acetylation were sonicated to obtain lower molecular weight samples
      and with low viscosity suitable for chemical modification and (13)C NMR
      experiments. The average degree of substitution (DS) of the polymer was estimated
      by Fourier transform infrared (FTIR) and NMR. (13)C NMR spectra were obtained and
      used to suggest a complete assignment of the signals. The nuclear Overhauser
      effect spectroscopy (NOESY) and heteronuclear multi-bond coherence (HMBC)
      experiments were used to elucidate connectivities between the various residues
      and deduce the linkage of these residues within the polysaccharide.

PMID- 11948441
TI  - Structural features of model glycopeptides in solution and in membrane phase: a
      spectroscopic and molecular mechanics investigation.
AB  - Model glycopeptides of the general formula Boc-Ala-Thr(G-D)-A(1)-A(2)-Leu-Leu
      Lys(N)-Ala-OMe, where D = dansyl (dimethyl aminonaphthalenesulphonyl), G =
      glucosyl and N = naphthyl, while A(1)-A(2) = Ala-Leu or Aib-Aib, and denoted as D
      G-Ala-N and D-G-Aib-N, respectively, were used to investigate glycoprotein
      membrane interactions. They carry two fluorophores (D and N), covalently linked
      to the glucose ring and the lysine side chain, respectively, while the threonine
      side chain is O-glycosylated. CD spectra in different solvent media suggest that
      both glycopeptides attain an ordered structure, possibly a helix-like
      conformation. By combining FRET (fluorescence resonance energy transfer)
      experiments with molecular mechanics data, the most probable structures of both
      glycopeptides were built up, starting from both a right-handed (rh) alpha- and
      3(10)-helix. They were found to populate an alpha-helical conformation, a result
      further confirmed by the very good agreement between theoretical and experimental
      quenching efficiency only observed when the backbone chain was in alpha-helix.
      The association of D-G-Ala-N with model membranes (liposomes) was studied by CD,
      fluorescence decay, fluorescence anisotropy, and collisional quenching
      experiments. The binding does not alter the structural features of the peptide
      because the CD spectral patterns are unaffected by the association. The peptide
      orientation inside the phospholipidic bilayer is guided by the polar glucose
      molecule lying in the water phase. The insertion of the hydrophobic backbone
      chain into the membrane, seeing the probes only partially accessible from the
      external solution, is characterized by a significant degree of heterogeneity, an
      increase in vesicles size, and a relevant stabilizing effect on the membrane
      itself against rupture by methanol.

PMID- 11948442
TI  - Recovery of small bioparticles by interfacial partitioning.
AB  - In this article, a qualitative study of the recovery of small bioparticles by
      interfacial partitioning in liquid-liquid biphasic systems is presented. A range
      of crystallised biomolecules with varying polarities have been chosen such as
      glycine, phenylglycine and ampicillin. Liquid-liquid biphasic systems in a range
      of polarity differences were selected such as an aqueous two-phase system (ATPS),
      water-butanol and water-hexanol. The results indicate that interfacial
      partitioning of crystals occurs even when their density exceeds that of the
      individual liquid phases. Yet, not all crystals partition to the same extent to
      the interface to form a stable and thick interphase layer. This indicates some
      degree of selectivity. From the analysis of these results in relation to the
      physicochemical properties of the crystals and the liquid phases, a hypothetical
      mechanism for the interfacial partitioning is deduced. Overall these results
      support the potential of interfacial partitioning as a large scale separation
      technology.

PMID- 11948443
TI  - Comparison of linear gradient and displacement separations in ion-exchange
      systems.
AB  - The linear gradient mode of chromatography is the most widely employed mode of
      operation in ion-exchange chromatographic separations. However, in recent years,
      the displacement mode has received considerable attention because of its promise
      of high throughput and high resolution. To enable a comparison of these two modes
      of chromatography, it is essential to identify the optimum operating conditions
      for each. We employed an iterative algorithm to carry out the necessary
      optimization. The Steric Mass Action model of ion-exchange chromatography is used
      in concert with the solid-film linear-driving force model to describe the
      chromatographic behavior of the solutes in these systems. The performances of
      displacement and gradient modes of chromatography are compared for different
      types of separation problems. It turns out that for "easy" separations, both the
      modes are equally effective. However, for challenging separations, the
      displacement mode is superior to the gradient mode. Our results shed significant
      light on the performance of gradient and displacement modes in protein ion
      exchange systems.

PMID- 11948444
TI  - Isolation of plasmid DNA from cell lysates by aqueous two-phase systems.
AB  - This work presents a study of the partitioning of a plasmid vector containing the
      cystic fibrosis gene in polyethylene glycol (PEG)/salt (K2HPO4) aqueous two-phase
      systems (ATPS). The plasmid was extracted from neutralized alkaline lysates using
      PEG with molecular weights varying from 200 to 8000. The effects of the lysate
      mass loaded to the ATPS (20, 40, and 60% w/w) and of the plasmid concentration in
      the lysate were evaluated. The performance of the process was determined by
      qualitative and quantitative assays, carefully established to overcome the strong
      interference of impurities (protein, genomic DNA, RNA), salt, and PEG. Plasmid
      DNA partitioned to the top phase when PEG molecular weight was lower than 400.
      The bottom phase was preferred when higher PEG molecular weights were used.
      Aqueous two-phase systems with PEG 300, 600, and 1000 were chosen for further
      studies on the basis of plasmid and RNA agarose gel analysis and protein
      quantitation. The recovery yields were found to be proportional to the plasmid
      concentration in the lysate. The best yields (>67%) were obtained with PEG 1000.
      These systems (with 40 and 60% w/w of lysate load) were able to separate the
      plasmid from proteins and genomic DNA, but copartitioning of RNA with the plasmid
      was observed. Aqueous two-phase systems with PEG 300 concentrated both plasmid
      and proteins in the top phase. The best system for plasmid purification used PEG
      600 with a 40% (w/w) lysate load. In this system, RNA was found mostly in the
      interphase, proteins were not detected in the plasmid bottom phase and genomic
      DNA was reduced 7.5-fold.

PMID- 11948445
TI  - Primary recovery of a genetically engineered Trichoderma reesei endoglucanase I
      (Cel 7B) fusion protein in cloud point extraction systems.
AB  - Here we present data to demonstrate how partitioning of a hydrophilic enzyme can
      be directed to the hydrophobic detergent-enriched phase of an aqueous two-phase
      system by addition of short stretches of amino acid residues to the protein
      molecule. The target enzyme was the industrially important endoglucanase I, EGI
      (endo-1,4-beta-D-glucan-4-glucanohydrolase, EC 3.2.1.4, Cel7B) of Trichoderma
      reesei. We investigated the partitioning of three EGI variants containing various
      C-terminal peptide extensions including Trp-Pro motifs of different lengths and
      localizations. Additionally, a recently developed system composed of the
      thermoseparating copolymer HM-EOPO was utilized to study the effects of fusion
      tags. The addition of peptides containing tryptohan residues enhanced the
      partitioning of EGI to the HM-EOPO-rich phase. The system composed of a nonionic
      detergent (Agrimul NRE1205) resulted in the highest partition coefficient (K =
      31) and yield (90%) with the construct EGI(core-P5)(WP)(4) containing (Trp
      Pro)(4) after a short linker stretch. A recombinant strain of T. reesei Rut-C30
      for large-scale production was constructed in which the fusion protein EGI(core
      P5)(WP)(4) was expressed from the strong promoter of the cellulase gene cbh1. The
      fusion protein was successfully expressed and secreted from the fungus during
      shake-flask cultivations. Cultivation in a 28-L bioreactor however, revealed that
      the fusion protein is sensitive to proteases. Consequently, only low production
      levels were obtained in large-scale production trials.

PMID- 11948446
TI  - Equilibrium modeling of extractive enzymatic hydrolysis of penicillin G with
      concomitant 6-aminopenicillanic acid crystallization.
AB  - In the present downstream processing of penicillin G, penicillin G is extracted
      from the fermentation broth with an organic solvent and purified as a potassium
      salt via a number of back-extraction and crystallization steps. After
      purification, penicillin G is hydrolyzed to 6-aminopenicillanic acid, a precursor
      for many semisynthetic beta-lactam antibiotics. We are studying a reduction in
      the number of pH shifts involved and hence a large reduction in the waste salt
      production. To this end, the organic penicillin G extract is directly to be added
      to an aqueous immobilized enzyme suspension reactor and hydrolyzed by extractive
      catalysis. We found that this conversion can exceed 90% because crystallization
      of 6-aminopenicillanic acid shifts the equilibrium to the product side. A model
      was developed for predicting the equilibrium conversion in batch systems
      containing both a water and a butyl acetate phase, with either potassium or D-p
      hydroxyphenylglycine methyl ester as counter-ion of penicillin G. The model
      incorporates the partitioning equilibrium of the reactants, the enzymatic
      reaction equilibrium, and the crystallization equilibrium of 6-aminopenicillanic
      acid. The model predicted the equilibrium conversion of Pen G quite reasonably
      for different values of pH, initial penicillin G concentration and phase volume
      ratio. The model can be used as a tool for optimizing the enzymatic hydrolysis.

PMID- 11948447
TI  - Synthesis of phosphatidylcholine with defined fatty acid in the sn-1 position by
      lipase-catalyzed esterification and transesterification reaction.
AB  - The incorporation of caproic acid in the sn-1 position of phosphatidylcholine
      (PC) catalyzed by lipase from Rhizopus oryzae was investigated in a water
      activity-controlled organic medium. The reaction was carried out either as
      esterification or transesterification. A comparison between these two reaction
      modes was made with regard to product yield, product purity, reaction time, and
      byproduct formation as a consequence of acyl migration. The yield in the
      esterification and transesterification reaction was the same under identical
      conditions. The highest yield (78%) was obtained at a water activity (a(w)) of
      0.11 and a caproic acid concentration of 0.8 M. The reaction time was shorter in
      the esterification reaction than in the transesterification reaction. The
      difference in reaction time was especially pronounced at low water activities and
      high fatty acid concentrations. The loss in yield due to acyl migration and
      consequent enzymatic side reactions was around 16% under a wide range of
      conditions. The incorporation of a fatty acid in the sn-1 position of PC proved
      to be thermodynamically much more favorable than the incorporation of a fatty
      acid in the sn-2 position.

PMID- 11948448
TI  - Effect of copy number and mRNA processing and stabilization on transcript and
      protein levels from an engineered dual-gene operon.
AB  - To study the effect of mRNA stability and DNA copy number on protein production
      from a dual-gene operon, a synthetic operon containing the reporter genes gfp and
      lacZ under the control of the araBAD promoter was placed in pMB1-based
      (approximately 100 copies/cell) and F plasmid-based (approximately 1 copy/cell)
      vectors. DNA cassettes encoding secondary structures were placed at the 5' and 3'
      ends of the genes and a putative RNase E site was placed between the two genes.
      Although the copy number of the pMB1-based vectors was approximately 100-fold
      greater than the copy number of the F plasmid-based vectors, transcript and
      protein levels from the pMB1-based vector were not 100-fold greater than from the
      F plasmid-based vectors. In identical plasmid backbones, different combinations
      of mRNA control elements were used to alter steady-state levels of transcripts.
      Control elements that amplified the stability of one coding region relative to
      another amplified the ratio of protein produced from those transcripts. The
      effects of mRNA stability control elements were greater at low inducer
      concentrations, where mRNA levels limit protein production, than at high inducer
      concentrations. Although we can alter mRNA and protein levels through copy
      number, induction level, and mRNA stability control elements, some aspect of gene
      expression remains dependent on inherent characteristics of the coding region.

PMID- 11948449
TI  - Evaluation of the performance of immobilized penicillin G acylase using active
      site titration.
AB  - Penicillin G acylase from Escherichia coli was immobilized on Eupergit C with
      different enzyme loading. The activity of the immobilized preparations was
      assayed in the hydrolysis of penicillin G and was found to be much lower than
      would be expected on the basis of the residual enzyme activity in the
      immobilization supernatant. Active-site titration demonstrated that the
      immobilized enzyme molecules on average had turnover rates much lower than that
      of the dissolved enzyme. This was attributed to diffusion limitations of
      substrate and product inhibition. Indeed, when the immobilized preparations were
      crushed, the activity increased from 587 U g-1 to up to 974 U g-1. The
      immobilized preparations exhibited up to 15% lower turnover rates than the
      dissolved enzyme in cephalexin synthesis from 7-ADCA and D-(-)-phenylglycine
      amide. The synthesis over hydrolysis ratios of the immobilized preparations were
      also much lower than that of the dissolved enzyme. This was partly due to
      diffusion limitations but also to an intrinsic property of the immobilized enzyme
      because the synthesis over hydrolysis ratio of the crushed preparations was much
      lower than that of the dissolved enzyme.

PMID- 11948451
TI  - Efficiency of embryoid body formation and hematopoietic development from
      embryonic stem cells in different culture systems.
AB  - Embryonic stem (ES) cells have tremendous potential as a cell source for cell
      based therapies. Realization of that potential will depend on our ability to
      understand and manipulate the factors that influence cell fate decisions and to
      develop scalable methods of cell production. We compared four standard ES cell
      differentiation culture systems by measuring aspects of embryoid body (EB)
      formation efficiency and cell proliferation, and by tracking development of a
      specific differentiated tissue type-blood-using functional (colony-forming cell)
      and phenotypic (Flk-1 and CD34 expression) assays. We report that individual
      murine ES cells form EBs with an efficiency of 42 +/- 9%, but this value is
      rarely obtained because of EB aggregation-a process whereby two or more
      individual ES cells or EBs fuse to form a single, larger cell aggregate.
      Regardless of whether EBs were generated from a single ES cell in methylcellulose
      or liquid suspension culture, or aggregates of ES cells in hanging drop culture,
      they grew to a similar maximum cell number of 28,000 +/- 9,000 cells per EB.
      Among the three methods for EB generation in suspension culture there were no
      differences in the kinetics or frequency of hematopoietic development. Thus,
      initiating EBs with a single ES cell and preventing EB aggregation should allow
      for maximum yield of differentiated cells in the EB system. EB differentiation
      cultures were also compared to attached differentiation culture using the same
      outputs. Attached colonies were not similarly limited in cell number; however,
      hematopoietic development in attached culture was impaired. The percentage of
      early Flk-1 and CD34 expressing cells was dramatically lower than in EBs cultured
      in suspension, whereas hematopoietic colony formation was almost completely
      inhibited. These results provide a foundation for development of efficient,
      scalable bioprocesses for ES cell differentiation, and inform novel methods for
      the production of hematopoietic tissues.

PMID- 11948450
TI  - Control of the redox potential by oxygen limitation improves bacterial leaching
      of chalcopyrite.
AB  - Shake flask and stirred tank bioleaching experiments showed that the dissolution
      of chalcopyrite is inhibited by ferric ion concentrations as low as 200 mg L(-1)
      and redox potentials >420 mV (vs. Ag/AgCl). Chemical leaching of chalcopyrite (4%
      suspension, surface area 2.3 m2 g(-1)) was enhanced fourfold in the presence of
      0.1 M ferrous sulphate compared with 0.1 M ferric sulphate. A computer-controlled
      reactor was designed to function as a "potentiostat"-bioreactor by arresting the
      air supply to the reactor when the redox potential in solution was greater than a
      designated setpoint. Leaching at a low, constant redox potential (380 mV vs.
      Ag/AgCl) achieved final copper recoveries of 52%-61%, which was twice that
      achieved with a continuous supply of oxygen (<30% extraction). The bacterial
      populations were observed to continue growing under oxygen limitation but in a
      controlled manner that was found to improve chalcopyrite dissolution. As the
      control mechanism is easily established and is likely to decrease production
      cost, the use of this technology may find application in industry.

PMID- 11948452
TI  - The effect of various substrates on cell attachment and differentiation of 3T3
      F442A preadipocytes.
AB  - The influence of extracellular matrix (Matrigel), collagen, and polylysine
      substrates on cell attachment and differentiation in 3T3-F442A preadipocytes was
      investigated. In comparison to an uncoated-polystyrene substrate, a concentrated
      Matrigel substrate (100 microg/cm2) markedly increased intracellular lipid level
      by about 30%, whereas a lower density Matrigel (10 microg/cm2) accelerated the
      differentiation rate but did not increase the amount of lipid 21 days after
      addition of adipogenic factors. Preadipocytes on the collagen surface
      differentiated less extensively than cells on the polystyrene. Polylysine did not
      effectively support attachment for either differentiated or undifferentiated
      cells. These results suggest that Matrigel provides the most suitable environment
      for both cell adhesion and differentiation for 3T3-F442A cells. This is in
      contrast to a previous report that extracellular matrix (from corneal endothelial
      cells) was detrimental to differentiation of 3T3-F442A cells.

PMID- 11948454
TI  - Continuous pH monitoring in a perfused bioreactor system using an optical pH
      sensor.
AB  - Monitoring and regulating the pH of the solution in a bioprocess is one of the
      key steps in the success of bioreactor operation. An in-line optical pH sensor,
      based on the optical absorption properties of phenol red present in the medium,
      was developed and tested in this work for use in NASA space bioreactors based on
      a rotating wall-perfused vessel system supporting a baby hamster kidney (BHK-21)
      cell culture. The sensor was tested over three 30-day and one 124-day cell runs.
      The pH sensor initially was calibrated and then used during the entire cell
      culture interval. The pH reported by the sensor was compared to that measured by
      a fiber optically coupled Shimadzu spectrophotometer and a blood gas analyzer.
      The maximum standard error of prediction for all the four cell runs for
      development pH sensor against BGA was +/-0.06 pH unit and for the fiber optically
      coupled Shimadzu spectrophotometer against the blood gas analyzer was +/-0.05 pH
      unit. The pH sensor system performed well without need of recalibration for 124
      days.

PMID- 11948453
TI  - Water-based nanoparticulate polymeric system for protein delivery: permeability
      control and vaccine application.
AB  - The idea of using polymeric nanoparticles as drug carriers is receiving an
      increasing amount of attention both in academia and industry, Nanoparticles have
      a number of potential applications in protein, drug and vaccine delivery, as well
      as gene therapy applications. In this article, we focus on this unique drug
      delivery technology as a method to control the release rate of substances, not
      only for protein delivery but also for delivering an experimental vaccine
      immunogen. Nanoparticles were assembled on the basis of ionic interaction between
      water-soluble polymers so that the resulting particles were stable in physiologic
      media. Among the typical polymers used to assemble nanoparticles, different
      polysaccharides, natural amines, and poly-amines were investigated. The entrapped
      substances tested included a protein and antigens. Polydextran aldehyde was
      incorporated into the particle core, to enable physiologic cross-linking as a
      method to control permeability. This resulted in long-term retention of
      substances that would otherwise rapidly leak out of the nanoparticles. Results of
      cross-linking experiments clearly demonstrated that the release rate could be
      substantially reduced, depending on the degree of cross-linking. For vaccine
      antigen delivery tests, we measured an antibody production after subcutaneous and
      oral administration. The data indicated that only the cross-linked antigen was
      immunogenic when the oral route of administration was used. The data presented in
      this article address primarily the utility of nanoparticulates for oral delivery
      of vaccine antigen.

PMID- 11948455
TI  - Human Ly-6 antigen E48 (Ly-6D) regulates important interaction parameters between
      endothelial cells and head-and-neck squamous carcinoma cells.
AB  - Selectin ligands are crucial components in the interaction between endothelial
      cells and extravasating cancer cells and, thus, play an important role in
      metastasis formation. Head-and-neck squamous cell carcinoma (HNSCC) variants
      expressing high levels of E48, a human Ly-6 protein (E48(hi)), expressed higher
      levels of the fucose-generating FX enzyme and of the fucosylated E-selectin
      ligand sLe(a) than cells expressing low levels of E48 (E48(lo)). Signaling
      through E48 upregulated expression levels of these molecules in HNSCC. In this
      work, we provide further evidence supporting the E48-FX-sLe(a) link by showing
      that FX antisense oligonucleotides reduced sLe(a) expression levels in HNSCC. We
      also show that E48 may be causally involved in regulating expression levels in
      HNSCC of 2 additional enzymes involved in the biosynthesis of sLe(a), namely, ST
      30 and FucTIII. Also, selectin-mediated adhesion of E48(hi) variants to activated
      HUVECs was significantly higher than that of E48(lo) variants. Transfection
      experiments utilizing sense or antisense E48 cDNA indicated that E48 may be
      causally involved in this adhesion. Chemokines are involved in the extravasation
      process of tumor cells. The release of chemoattractants from HNSCC variants
      differing in E48 expression was therefore analyzed. HNSCC did not release any
      chemoattractants but induced the release of such factors from HUVECs.
      Supernatants from E48(hi) variants were significantly more efficient than E48(lo)
      cells at inducing the release of chemoattractants from HUVECs. Transfection
      experiments indicated that E48 may be causally involved in the induction of
      chemoattractant release from HUVECs. Angiogenesis is an important manifestation
      of cancer-endothelium interactions. We therefore assayed for the presence of
      angiogenic factors in culture supernatants of HNSCC. Supernatants from E48(lo)
      variants contained significantly higher amounts of PDGF than E48(hi) cells.
      Transfection experiments indicated that E48 may be causally involved. Taken
      together, our results suggest that E48 controls important interaction parameters
      between HNSCC and endothelial cells.

PMID- 11948456
TI  - Specific induction of gadd45 in human melanocytes and melanoma cells after UVB
      irradiation.
AB  - The purpose of our study was to analyze the p53-mediated response of human
      melanocytes and human melanoma cells to UVB (natural environmental carcinogen) or
      UVC irradiation (experimental carcinogen). A semi-quantitative RT-PCR method was
      developed to allow the analysis of the expression of 5 p53 effector genes
      (p21(WAF1), mdm2, cyclin G1, gadd45, bax) at the same time with a small amount of
      RNA (1 microg). In human melanocytic cells, the p53 downstream genes were found
      to be differentially activated after UVB and UVC irradiation. After UVB
      irradiation, p53 protein accumulation was sustained up to 48 hr that was not the
      case after UVC irradiation. Among the p53 effector genes tested, gadd45 was the
      only 1 to show a strong and specific induction after UVB irradiation. With high
      UVB doses, gadd45 was also the only gene to be transcribed. By contrast, after
      UVC irradiation, all the p53 effector genes tested were transcriptionally
      induced. Experiments conducted with fibroblasts and keratinocytes didn't show
      such a striking activation of gadd45 after UVB irradiation. These results point
      out the potential role of gadd45 in response to UVB irradiation in human
      melanocytes and the different p53-mediated responses to different carcinogens.

PMID- 11948457
TI  - PPARgamma-mediated antineoplastic effect of NSAID sulindac on human oral squamous
      carcinoma cells.
AB  - There is strong evidence that nonsteroidal antiinflammatory drug (NSAID) sulindac
      may exert a significant antineoplastic effect. The purpose of our study was to
      explore the effects of sulindac on human oral squamous cell carcinoma (SCCa)
      cells and to elucidate the underlying molecular mechanisms. The changes that
      sulindac treatment induced on growth, apoptosis and cell cycle distribution of
      human oral SCCa cell lines were assessed by cell growth and flow cytometry
      experiments. Utilizing quantitative RT-PCR and immunocytochemistry, we determined
      the effect of sulindac treatment on mRNA and protein expression of different
      sulindac's targets. Also, PPARgamma expression was selectively targeted by
      antisense oligonucleotide treatment. Both sulfide and sulfone metabolites of
      sulindac, which differ in the ability to cause COX-2 inhibition, induced a
      significant dose- and time-dependent cell growth reduction accompanied by
      increase in apoptosis without concomitant cell cycle arrest. Sulindac treatment
      also caused upregulation of the protein and mRNA expression levels of COX-2 and
      PPARs. Treatment with antisense PPARgamma oligonucleotides abolished sulindac's
      growth inhibitory effect. Our results are consistent with a significant growth
      inhibitory effect of NSAID sulindac on human oral SCCa cells, which is mediated,
      at least partially, through induction of apoptosis. We suggest that upregulation
      of PPARgamma expression and activation may be, at least partially, responsible
      for sulindac's antiproliferative effect.

PMID- 11948458
TI  - Effects of transforming growth factor-beta1 and tumour necrosis factor-alpha on
      cultured fibroblasts from skin fibroma as modulated by toremifene.
AB  - To determine how toremifene, an anti-oestrogen triphenylethylene derivate,
      reduces tumour mass, we investigated its modulation of TGF-beta1 and TNF-alpha in
      fibroma fibroblasts. Normal and fibroma fibroblasts, isolated from patients
      affected by Gardner's syndrome without or with fibroma manifestation, were
      cultured in vitro. Secretion of GAG, collagen and TGF-beta1 was increased in
      fibroma fibroblasts compared to healthy cells. The increase in TGF-beta1
      secretion into the medium was associated with a parallel increase in TGF-beta1
      gene expression and receptor number. Receptor cross-linking studies using
      radiolabelled TGF-beta1 revealed more receptors, particularly types I and II, in
      fibroma fibroblasts than in normal cells. Normal and fibroma fibroblasts did not
      synthesise TNF-alpha, but they had TNF-alpha membrane receptors, as shown by TNF
      alpha assay. TNF-alpha secreted by human monocytes, which may be present in the
      peritumoral area, increased cell proliferation and GAG accumulation and was, in
      turn, enhanced by TGF-beta1 treatment. Both growth factors increased
      angiogenesis, as shown by the CAM assay. Toremifene reduced TGF-beta1 secretion
      by fibroma fibroblasts and TNF-alpha secretion by monocytes, thus downregulating
      cell proliferation, ECM macromolecule accumulation and angiogenic progression. We
      hypothesise that increased TGF-beta1 gene expression and TGF-beta1 secretion in
      fibroma fibroblasts as well as the subsequent rise in TNF-alpha production by
      monocytes may facilitate fibroma growth and that toremifene inhibits autocrine
      and paracrine growth factor production.

PMID- 11948459
TI  - Status of c-erbB-2 in gastric adenocarcinoma: a comparative study of
      immunohistochemistry, fluorescence in situ hybridization and enzyme-linked immuno
      sorbent assay.
AB  - c-erb-2 amplification and overexpression are currently attracting a great deal of
      attention because a new adjuvant therapy using an antibody against the c-erbB-2
      gene product, trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA),
      has proved effective in treating breast cancer with amplification and/or
      overexpression of c-erbB-2. Aberrations of c-erbB-2 have also been detected in
      ovarian, endometrial and gastric carcinomas at varied frequencies. Amplification
      of the c-erbB-2 locus (17q12-q21.32), overexpression of c-erbB-2 protein (p185)
      and serum levels of soluble c-erbB-2 protein fragments (p105) were examined in
      gastric cancer patients using fluorescence in situ hybridization (FISH),
      immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively.
      Overexpression of c-erbB-2 protein was found in 29 (8.2%) of the 352 gastric
      carcinomas analyzed. In FISH analysis, all tumors with 3+ immunostaining and 1 of
      5 tumors with 2+ staining showed high-level amplification of c-erbB-2. Pre
      operative serum p105 was quantified in serum specimens from 129 patients with
      gastric cancer and 28 patients with benign diseases. There were no significant
      differences in the serum p105 levels among 11 patients with c-erbB-2
      overexpressing carcinomas, 118 patients with c-erbB-2 non-overexpressing
      carcinomas and 28 controls, although a single case of gastric carcinoma
      overexpressing c-erbB-2 with extensive liver metastasis had a higher level than
      the cut-off value. The mechanisms of overexpression of p185 and high-level
      amplification of c-erbB-2 in gastric adenocarcinomas seem similar to those well
      established in breast cancers. Patients having gastric adenocarcinoma with c-erbB
      2 amplification are potential candidates for a new adjuvant therapy using
      humanized monoclonal antibody.

PMID- 11948460
TI  - Germline mutations in E-cadherin do not explain association of hereditary
      prostate cancer, gastric cancer and breast cancer.
AB  - Somatic mutations in the E-cadherin (CDH1) gene have frequently been reported in
      cases with diffuse gastric and lobular breast cancers. Recently, germline
      mutations have been identified in families with diffuse gastric cancers. In
      families with hereditary prostate cancer (HPC), a significant association of
      prostate cancer, gastric and/or breast cancer has been observed in
      epidemiological studies. The aim of this study was to investigate if germline
      mutations in CDH1 could explain the risk for cancer in HPC families with an
      excess of gastric and breast cancer. In total, 17 members from 13 HPC families
      and 3 members from 3 families with hereditary gastric cancer (HGC) were screened
      for germline CDH1 sequence alterations using PCR/Denaturing HPLC for initial
      screening of nucleotide variants followed by confirmatory direct sequencing
      analysis. The frequency of identified novel germline mutations were tested for in
      136 cases with hereditary prostate cancer and 215 cases of sporadic prostate
      cancer with 422 age matched controls in an allelic discrimination assay. In
      total, 8 sequence variants were detected in 20 samples tested. In the HPC
      families, we found 2 missense mutations, A592T in exon 12 and a novel D777N in
      exon 15 and a mutation in intron 5, 687+92T>A. A previously known polymorphism in
      exon 13 and 3 sequence variations in introns and untranslated regions were also
      found, of which the significance is unknown. In HGC-023 with early onset diffuse
      gastric cancer a truncating mutation, R335X, was identified in exon 7. None of
      the missense mutations or 687+92T>A were found in the extended HPC material or in
      the sporadic prostate cancer cases with age-matched controls in the allelic
      discrimination assay. We found several germline mutations of unknown clinical
      significance in the CDH1 gene that probably do not explain the association of
      prostate, gastric and/or breast cancers in the HPC-families. Two missense
      mutations and a mutation in intron 5 were identified that do not influence the
      risk of hereditary or sporadic prostate cancer in general and are considered to
      be pedigree specific. In a family with hereditary gastric cancer of the diffuse
      type, we identified the first truncating germline mutation in a Scandinavian
      family.

PMID- 11948462
TI  - Telomerase activity and hTERT mRNA expression can be heterogeneous and does not
      correlate with telomere length in soft tissue sarcomas.
AB  - In a previous study, we showed that telomerase activity (TA) and human telomerase
      reverse transcriptase (hTERT) mRNA expression were undetectable in benign
      mesenchymal lesions and low-grade soft tissue sarcomas (STSs), but detectable in
      about 50% of intermediate-/high-grade STSs. We wondered if this lack of TA or
      hTERT mRNA expression could be related to the tumor sample examined and if there
      was a relationship between the former 2 parameters and telomere length. Two
      separate tumor samples from 37 STSs were examined for telomerase activity, using
      the telomerase repeat amplification protocol (TRAP) assay and for hTERT mRNA
      expression, using RT-PCR. Telomere length was determined in each tumor sample,
      using the terminal restriction fragments (TRF) technique. Significant variations
      in telomere length, TA and hTERT mRNA expression between 2 samples of the same
      tumor were observed in 27%, 11% and 27% of STSs, respectively. Telomere length
      did not correlate with TA or hTERT mRNA expression. Despite great intratumoral
      heterogeneity in telomere length, short and long telomeres were more often seen
      in the low/intermediate-grade and high-grade STS categories, respectively. Few
      STSs that showed a TRF pattern suggestive of alternative lengthening of telomeres
      (ALT) may contain ALT subpopulations.

PMID- 11948461
TI  - Evidence for an age-related influence of microsatellite instability on colorectal
      cancer survival.
AB  - It is well established that microsatellite instability (MSI), the hallmark of
      defective DNA mismatch repair (MMR), is associated with prolonged survival in
      colorectal cancer compared with tumours that are microsatellite stable (MSS). MSI
      in sporadic colorectal tumours is primarily due to epigenetic silencing of MLH1.
      However, there are no prospective population-based studies of survival in
      patients with germline MMR gene mutations who develop cancer. Although MSI is
      almost universal in tumours from HNPCC family members, there is a potential
      confounding effect of ascertainment and other biases that could explain the
      apparent survival benefit in HNPCC families. Resolving whether germline MMR gene
      mutations impact on survival is important because it potentially undermines the
      rationale for surveillance of mutation carriers. Here, we report an investigation
      of the influence of MSI on survival in cohorts of cancer patients (aged < 30
      years at diagnosis, n = 118; non-age-selected, n = 181) in the context of
      clinicopathologic variables. There was a substantial age-related influence of
      tumour MSI status on survival. In young patients with tumour MSI, 65% of patients
      with MSI tumours had germline MSH2 or MLH1 mutations. Clinicopathologic variables
      and tumour MSI of the cohort were studied with respect to survival and compared
      with control groups. Young patients had excess MSI tumours (p < 0.000001),
      mucinous tumours (p < 0.01), advanced disease (p approximately 0.001) and poorer
      5-year survival compared with older cases. Cox proportional hazard analysis
      identified Dukes' stage, age at diagnosis and calendar year of treatment as
      independent predictors of survival. There was no detectable association between
      tumour MSI and survival in young patients, although we confirmed previous
      observations that MSI is associated with better prognosis in later onset cohorts.
      These findings underscore the rationale for surveillance and early identification
      of tumours in MMR gene carriers as well as refining understanding of the
      influence of MSI on cancer progression.

PMID- 11948463
TI  - Tumor-targeted immune complex formation: effects on myeloid cell activation and
      tumor-directed immune cell migration.
AB  - The effectiveness of cellular immunotherapy of solid tumors is often hampered by
      the lack of specific infiltration of immune effector cells into the tumor mass.
      Therefore, we studied the potential of tumor antigen-specific antibodies to
      elicit tumor-specific myeloid cell activation, to induce or enhance tumor
      infiltration by immune cells. To this end, we developed an in vitro model system
      using the human myeloid cell line MonoMac-6. Incubation of IFN-gamma-primed
      MonoMac-6 cells with serum-opsonized zymosan or EGP-2-directed, mouse IgG2a
      opsonized, EGP-2-positive tumor cells resulted in the production of ROS and TNF
      alpha and induced E-selectin and ICAM-1 expression on HUVECs. FcR-mediated
      MonoMac-6 cell activation was strictly dependent on the activation of MonoMac-6
      cells with IFN-gamma. In addition, no myeloid cell activation was observed in the
      presence of human serum or using tumor antigen-specific mouse antibody subclasses
      other than IgG2a, suggesting the crucial involvement of CD64 (FcgammaR1) in the
      effects observed. However, serum-inhibited myeloid cell activation was completely
      restored employing a 2-step targeting approach in which tumor cell opsonization
      with mouse anti-EGP-2 antibodies was followed by incubation with human antimouse
      Ig antibodies. Moreover, using this 2-step approach, not only anti-EGP-2-directed
      mouse IgG2a but also mouse IgG1 antibodies effectively induced tumor-specific
      myeloid cell activation. In conclusion, we describe a method to induce efficient
      and tumor-specific activation of myeloid cells based on the sequential use of
      mouse tumor antigen-specific and human antimouse Ig antibodies. Targeted myeloid
      cell activation may provide a means to aid in the induction of a tumor-directed
      immune response and as such, the method described here could be of clinical
      significance.

PMID- 11948464
TI  - HER-2/neu-derived peptide epitopes are also recognized by cytotoxic CD3(+)CD56(+)
      (natural killer T) lymphocytes.
AB  - The human HER-2/neu gene encodes a 185 kDa transmembrane glycoprotein recognized
      by MHC class I-restricted CTLs. Here, we report that HER-2/neu peptide CTL
      epitopes can also be recognized by cytotoxic NK-T lymphocytes. Unfractionated
      peptides derived from HLA-A2(+), HER-2/neu(+) tumor cells acid cell extract
      (ACE), collected from patients with metastatic ovarian cancer, were used as
      antigen to generate in vitro cytotoxic effectors. ACE was able to elicit from
      cancer patients' PBMCs both alphabetaTCR(+)CD3(+)CD56(-) and
      alphaTCR(+)CD3(+)CD56(+) (NK-T) CTLs that lysed ACE-sensitized T2 cells in an HLA
      A2-restricted manner. The same CTL lines also recognized T2 cells pulsed with HER
      2/neu-derived CTL peptide epitopes, a HER-2/neu-transfected HLA-A2(+) cell line
      and autologous tumor cells. alphaTCR(+)CD3(+)CD56(+) CTL lines also exhibited NK
      like cytotoxicity against autologous tumor cells. CTL clones were isolated from
      alphaTCR(+)CD3(+)CD56(+) bulk cultures displaying both MHC- and non-MHC
      restricted cytotoxicity, thus confirming the dual cytolytic function of such
      cells. Our data demonstrate that ACE from metastatic ovarian tumors can be used
      as multiepitope vaccines for generating in vitro, besides classical CTLs, NK-T
      cells exerting efficient MHC- and non-MHC-restricted cytotoxicity against
      autologous tumor targets. Such NK-T cells expressing dual cytotoxic activity may
      prove advantageous in cancer immunotherapy.

PMID- 11948465
TI  - Expression of interleukin-18 in human ovarian carcinoma and normal ovarian
      epithelium: evidence for defective processing in tumor cells.
AB  - Interleukin-18 (IL-18) is a proinflammatory monokine structurally related to IL
      1beta that stimulates interferon-gamma (IFN-gamma) production. IL-18 is
      synthesized as an inactive precursor, pro-IL-18, which is cleaved by IL-1beta
      converting enzyme (ICE)/caspase-1 in a mature protein. In view of the proposed
      use of IL-18 in cancer immuno/gene therapy, we have studied the expression of IL
      18 in tumor cells. IL-18 mRNA was detected by reverse transcriptase polymerase
      chain reaction in all human ovarian carcinoma cell lines tested (9/9) and in one
      half of tumor cell populations obtained from ovarian carcinoma patients (4/8).
      ICE mRNA was expressed in a smaller fraction of samples (3/9 cell lines and 3/8
      samples from patients). IL-18 protein was also found in 7/13 ovarian carcinoma
      solid tumors by immunohistochemic analysis. In tumor cell lines we were able to
      detect abundant intracellular pro-IL-18 (24 kDa) by Western blotting, whereas the
      mature form of IL-18 was undetectable, irrespective of the presence of ICE mRNA
      and protein. Only pro-IL-18 was also found in the ovarian carcinoma cell
      supernatants, which did not display any IL-18 biologic activity in functional
      assays. Normal cultured ovarian epithelial cells revealed the presence of both IL
      18 and ICE mRNA in all samples (5/5) and IL-18 protein was expressed by the thin
      epithelial cell layer surrounding normal ovary. More importantly, normal ovarian
      epithelial cells released low but detectable amounts of mature IL-18 in the
      culture supernatant, which displayed IL-18-like biologic activity in functional
      assays. These data suggest that mature biologically active IL-18 production is a
      feature of the normal ovarian surface epithelium lost during neoplastic
      transformation.

PMID- 11948466
TI  - High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients.
AB  - The prognostic significance of BRCA2 mRNA levels in tumor tissues was studied in
      sporadic breast cancer patients. BRCA2 mRNA levels were determined by real-time
      PCR. Histologic grade III tumors showed significantly (p = 0.001) higher BRCA2
      mRNA levels (0.828 +/- 0.102 BRCA2/beta-glucuronidase mRNA ratio, mean +/- SE)
      than histologic grade I and II tumors (0.438 +/- 0.055) and estrogen receptor
      (ER)-negative tumors (0.773 +/- 0.102) showed a nonsignificant (p = 0.072) trend
      toward an increase in BRCA2 mRNA levels compared to ER-positive tumors (0.541 +/-
      0.079). Other clinicopathologic parameters, such as menopausal status, lymph node
      status and tumor size, were not significantly associated with BRCA2 mRNA levels.
      Patients with high BRCA2 mRNA levels showed a significantly (p = 0.006) lower 5
      year disease free survival rate (63%) than those with low levels (94%). Lymph
      node metastases, ER negativity and high histologic grade were also significantly
      (p < 0.05) associated with poor prognosis. Multivariate analysis revealed that
      BRCA2 mRNA levels were a significant prognostic factor, being independent of the
      other conventional prognostic factors. Our results suggest that BRCA2 mRNA levels
      might serve as a clinically useful prognostic factor in breast cancer patients.

PMID- 11948467
TI  - Prognostic significance of Ep-CAM AND Her-2/neu overexpression in invasive breast
      cancer.
AB  - To assess the frequency and prognostic impact of Ep-CAM and Her-2/neu
      overexpression in patients with breast cancer and to determine its relationship
      with other prognostic markers, 205 breast cancer patients with a median follow-up
      of 10.8 years were enrolled in this retrospective study. Overexpression of Ep-CAM
      and Her-2/neu in tumor tissue samples was assessed by immunohistochemistry.
      Tumors presenting a Her-2/neu 2+ staining were additionally analyzed by FISH to
      exclude false positive results. Ep-CAM and Her-2/neu overexpression was found in
      35.6% and 19.5% of the tumor samples, respectively. Both Ep-CAM and Her-2/neu
      overexpression were predictive for poor disease-free (DFS) and disease-related
      overall survival (DROS). Concurrent Ep-CAM and Her-2/neu overexpression was
      present in 13.2% of tumor specimens and had an additive negative impact on DFS
      and DROS. This minority of patients had a median time to relapse of only 34
      months, whereas the median time to relapse was not reached in the patient
      population without Her-2/neu and Ep-CAM overexpression. By multivariate analysis
      Ep-CAM overexpression proved to be an indicator of poor prognosis, independent of
      tumor size, histologic grade, hormone receptor expression and Her-2/neu
      overexpression. In conclusion, overexpression of Ep-CAM and Her-2/neu complement
      each other as predictors for poor prognosis in patients with invasive breast
      cancer. Determination of these tumor markers should help in assigning breast
      cancer patients to 1 of 3 distinct risk categories.

PMID- 11948469
TI  - Molecular classification of borderline ovarian tumors using hierarchical cluster
      analysis of protein expression profiles.
AB  - Ovarian tumors range from benign to aggressive malignant tumors, including an
      intermediate class referred to as borderline carcinoma. The prognosis of the
      disease is strongly dependent on tumor classification, where patients with
      borderline tumors have much better prognosis than patients with carcinomas. We
      here describe the use of hierarchical clustering analysis of quantitative protein
      expression data for classification of this type of tumor. An accurate
      classification was not achieved using an unselected set of 1,584 protein spots
      for clustering analysis. Different approaches were used to select spots that were
      differentially expressed between tumors of different malignant potential and to
      use these sets of spots for classification. When sets of proteins were selected
      that differentiated benign and malignant tumors, borderline tumors clustered in
      the benign group. This is consistent with the biologic properties of these
      tumors. Our results indicate that hierarchical clustering analysis is a useful
      approach for analysis of protein profiles and show that this approach can be used
      for differential diagnosis of ovarian carcinomas and borderline tumors.

PMID- 11948468
TI  - High frequency of serum DNA alterations in renal cell carcinoma detected by
      fluorescent microsatellite analysis.
AB  - To date there are no reliable serological markers for renal cell carcinoma (RCC).
      We applied fluorescent microsatellite analysis (MSA) to detect serum DNA
      alterations in patients with RCC. Fresh tumour, peripheral blood and serum
      specimens from 60 consecutive patients treated for malignant renal tumours (n= 53
      RCC and n= 7 non-RCC) were prospectively collected. After DNA extraction, we
      performed MSA with a total of 9 markers from the chromosomal regions 3p, 5q, 7p,
      7q, 9p, 13q, 17p and 17q to identify tumour specific serum DNA alterations in
      Group I (n= 53 RCC); 11 additional markers were used in the first 23 RCCs (Group
      II) in order to increase sensitivity; and 20 healthy controls were investigated
      with 10 markers. Besides the histomorphological diagnosis the RCCs were
      genetically stratified according to the "Heidelberg Classification" of renal
      tumours. Detection of allelic imbalance and loss of heterozygosity (LOH) was
      carried out on an automated laser sequencer. In Group I we identified serum DNA
      alterations in 74% (39/53) of cases. When applying 20 markers, the sensitivity
      was elevated to 87% (20/23) in Group II. Investigating 20 healthy controls with
      10 markers, the method rendered 85% specificity. The highest incidence of
      alterations was detected for chromosomal regions 3p and 5q. The presence of serum
      DNA alteration was not associated with tumour nuclear grade but exhibited a trend
      towards advanced stages (p = 0,044). In RCC, the microsatellite analysis has a
      high sensitivity in the detection of serum DNA alterations when a sufficient
      number of markers from various chromosomal regions are used. Advanced tumours
      tend to express serum DNA alterations more frequently.

PMID- 11948470
TI  - Histologic classification of thymic epithelial tumors: comparison of established
      classification schemes.
AB  - The object of our multicenter retrospective study was to compare the new
      histologic World Health Organization (WHO) classification and the classical
      histologic Bernatz classification in terms of interobserver agreement and
      prognostic importance. The influence of coexisting diseases was also analyzed
      using the Charlson score. We evaluated 218 patients from 5 different hospitals
      who were treated between 1967 and 1998. The statistical methods of analysis
      included Kaplan-Meier estimates of survival curves and the application of Cox
      proportional hazards models to identify sets of prognostic factors for survival.
      Interobserver agreement was assessed by kappa coefficients. For both WHO and
      Bernatz classifications, interobserver agreement was good (weighted kappa >
      0.87). However, the subdiversification of the "bioactive" WHO subgroup (B1, B2,
      B3) resulted in an interobserver agreement of only 0.49 within this group. In
      multivariable models, both the WHO classification and the Bernatz classification
      including carcinomas showed similar prognostic capabilities. The B3 type in the
      WHO classification and the predominantly epithelial type in the Bernatz
      classification had an intermediate prognostic ranking in comparison with the
      carcinomas and with the other subgroups. For both classifications, further
      simplification and subclassification into 3 subgroups led to classes with good
      discriminative power in respect to survival. In addition, very good interobserver
      agreement was observed in the simplified classifications. Comorbidity, sex, age
      of the patient and lymphofollicular hyperplasia had no major influence on overall
      survival. Both classifications showed similar prognostic power. Interobserver
      agreement of the type B subgroups was only moderate. By simplification of the
      classifications, subgroups with distinct survival could be identified.

PMID- 11948471
TI  - Completeness and accuracy of registration of ovarian cancer in the cancer
      registry of Norway.
AB  - Completeness of reporting and accuracy of the diagnosis of ovarian cancer from
      one health region in Norway to the Cancer Registry were examined. Data kept by
      the Cancer Registry were evaluated against discharge diagnosis data from all 8
      hospitals in the health region during the period of 1987-1996. The assessment of
      the accuracy of the diagnosis recorded in the Cancer Registry was based on review
      of all medical records in the hospital setting and on slide review of all
      histologic diagnoses. The overall completeness of reporting ovarian cancer to the
      Cancer Registry was 99.6%. The organ specific completeness of registration of
      histologic verified ovarian cancer within the Cancer Registry was 95.3%; 0.9% was
      erroneously coded and 3.5% had their diagnosis changed to ovarian cancer at re
      evaluation. Of all ovarian cancer cases registered at the Cancer Registry, 91%
      had a primary histologic diagnosis. Among 591 cases identified with a histologic
      diagnosis in the Cancer Registry, the accuracy of the diagnosis was estimated at
      92%. Coding errors were found in 2% of these cases, while in 6% of the cases it
      was not possible to reproduce the original diagnosis of ovarian cancer at re
      evaluation. In order to provide data of high quality for cancer surveillance a
      cancer registry needs several data providers, such as histopathologic laboratory
      reports and clinical reports. In addition, assessment of reported data through
      stringent quality assurance procedures within the registry are necessary for
      reaching a nearly 100% completeness of registration as found for ovarian cancer
      in the Cancer Registry of Norway.

PMID- 11948472
TI  - Grand multiparity and incidence of endometrial cancer: a population-based study
      in Finland.
AB  - The hormonal background of endometrial cancer is insufficiently characterised. We
      investigated the significance of parity, age at first birth, intensity between
      births, length of time from the first to the last birth and length of delivery
      free premenopausal period in a cohort of grand multiparous (GM) women, i.e.,
      women with at least 5 births. Data of the Population Register of Finland (86,978
      GM-women) and the population-based Finnish Cancer Registry were combined.
      Standardised incidence ratios (SIRs) were calculated by dividing the number of
      observed cancer cases by the expected number based on the national incidence
      rates. Multivariate relative risks (RRs) were estimated by Poisson regression
      analysis. The SIR for endometrial cancer among GM-women was low [419 cases;
      SIR=0.57, 95% confidence interval (CI) 0.52-0.63]. The RR of endometrial cancer
      was 0.58 (95% CI 0.34-0.97) among women giving their first birth at an age of
      more than 30 years compared to women with first birth before the age of 20. In
      ages 50+ (94% of endometrial cancer cases), the RR for women with at least 8
      births was 0.63 (95% CI 0.44-0.92) compared to those with 5 births, and those
      with a birth period of 20+ years had RR=0.57 (95% CI 0.34-0.96) compared to those
      with a period of <10 years, while prolonged average intensity between births
      showed only a small protective effect. The RR of endometrial cancer also
      correlated with the length of premenopausal delivery-free period (RR = 0.61, 95%
      CI 0.44-0.86) for women with a short (<10 years) period compared to women with a
      long (>15 years) period. Our findings, that a large number of births, old age at
      first birth, a long birth period and a short premenopausal delivery-free period
      reduced the risk of postmenopausal endometrial cancer of GM-women, emphasise the
      protective role of progesterone and the stimulatory role of estradiol in the
      hormonal background of this disease.

PMID- 11948473
TI  - Effect of highly active antiretroviral therapy on survival among HIV-infected men
      with Kaposi sarcoma or non-Hodgkin lymphoma.
AB  - The effect of highly active antiretroviral therapy (HAART) on survival in HIV
      infected patients with Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL) is
      unknown. Our study examines survival after HAART for these 2 malignancies.
      Analyses were performed using data from 387 HIV-infected men in the Multicenter
      AIDS Cohort Study (MACS) after a diagnosis of either KS or NHL in 1990-99.
      Potential prognostic factors, including HAART, were evaluated in univariate
      analyses using Kaplan-Meier survival curves and log-rank tests. Multivariate
      survival analyses were conducted using Cox's time-dependent proportional hazards
      models, adjusting for CD4(+) cell levels at the time of cancer diagnosis and
      other covariates. Forty-three of 287 KS patients (15%) and 13 of 100 NHL patients
      (13%) had been treated with HAART. HAART treatment was associated with improved
      survival for KS and NHL patients (log-rank p = 0.0001 for each group). In
      multivariate analyses, HAART was associated with an 81% reduced risk of death
      among KS patients [relative hazard (RH) 0.19, 95% confidence limits (CL) (0.08,
      0.45)], compared to those not exposed to HAART and an 84% reduced risk [RH 0.16,
      95% CL (0.04, 0.64)] among NHL patients. Relative hazards estimates were similar
      for those with HAART initiation before and after NHL diagnosis. The use of HAART
      prolongs overall survival among HIV-positive men diagnosed with KS and NHL. HAART
      appears to be effective in improving survival even when initiated after the
      diagnosis of NHL and KS.

PMID- 11948474
TI  - Inhibition of prostate carcinoma establishment and metastatic growth in mice by
      an antiangiogenin monoclonal antibody.
AB  - A neutralizing monoclonal antibody (MAb) 26-2F to human angiogenin, a potent
      inducer of neovascularization, has been shown previously to prevent or delay the
      appearance of angiogenin-secreting human colon, fibrosarcoma and lung tumor cell
      xenografts implanted subcutaneously (s.c.) into athymic mice. In an analogous
      model system, we report here that the antibody also prevents the establishment of
      PC-3 androgen-independent human prostate cancer tumors in, on average, 40% of
      treated mice (p < 0.0001, survivor analysis). Intriguingly, combining MAb 26-2F
      together with cisplatin and suramin, 2 therapeutic agents that together showed
      little antitumor activity in the aforementioned model, resulted in an even
      greater degree of protection (71% protected, p = 0.009 compared to antibody
      treatment alone). This protective effect persisted several weeks after cessation
      of treatment. Additionally, prophylactic systemic administration of MAb 26-2F
      dramatically reduced by 50% the formation of spontaneous regional metastasis
      originating from primary growth in the prostate gland of PC-3M cells, highly
      metastatic variants of PC-3. Protection from metastasis was still significant
      when treatment with MAb 26-2F was delayed until after the primary tumor was well
      established. The antibody is not directly cytotoxic to either cell type, both of
      which secrete angiogenin in vitro and when growing as tumors in vivo, but changes
      the pattern of vascularity in primary tumors growing orthotopically. These
      findings, together with the observation that angiogenin protein and mRNA are
      apparently overexpressed in cancerous vs. normal human prostate tissues,
      demonstrate that angiogenin antagonism represents a promising new approach for
      preventing progression and metastasis of clinical prostate cancer.

PMID- 11948476
TI  - Transmission/disequilibrium tests of androgen receptor and glutathione S
      transferase pi variants in prostate cancer families.
AB  - Population-based case-control studies have found relationships between risk of
      prostate cancer and genetic polymorphisms in the CAG repeat and GGC repeat of the
      X-linked androgen receptor gene (AR) as well as the autosomal gene coding for
      glutathione S-transferase pi (GSTP1). This family-based study utilized the
      transmission disequilibrium test to examine whether there was evidence that these
      polymorphisms could account for familial aggregation of prostate cancer. Seventy
      nine North American pedigrees were studied. Most of these families had 3 or more
      affected first-degree relatives. Genotype information was obtained on 578
      individuals. The reconstruction combined transmission disequilibrium test (RC
      TDT) was used to test for linkage. There was no evidence of linkage to the CAG
      and GGC repeat sequences in the AR gene or the pentanucleotide (ATAAA) repeat in
      the GSTP1 gene when each allele was analyzed separately or when alleles were
      grouped by repeat length. Our findings do not support the hypothesis that
      familial clustering of prostate cancer in high-risk families is attributable to
      these genetic variants.

PMID- 11948475
TI  - Neuroendocrine tumor targeting: study of novel gallium-labeled somatostatin
      radiopeptides in a rat pancreatic tumor model.
AB  - Somatostatin analogs labeled with radionuclides are of considerable interest in
      the diagnosis and therapy of SSTR-expressing tumors, such as
      gastroenteropancreatic, small cell lung, breast and frequently nervous system
      tumors. In view of the favorable physical characteristics of the Ga isotopes
      (67)Ga and (68)Ga, enabling conventional tumor scintigraphy, PET and possibly
      internal radiotherapy, we focused on the development of a Ga-labeled somatostatin
      analog suitable for targeting SSTR-expressing tumors. For this purpose, 3
      somatostatin analogs, OC, TOC and TATE were conjugated to the metal chelator DOTA
      and labeled with the radiometals (111)In, (90)Y and (67)Ga. They were then
      evaluated for their performance in the AR4-2J pancreatic tumor model by testing
      SSTR2-binding affinity, internalization/externalization in isolated cells and
      biodistribution in tumor-bearing nude mice. Surprisingly, we found that, compared
      to (111)In or (90)Y, labeling with (67)Ga considerably improved the biologic
      performance of the tested somatostatin analogs with respect to SSTR2 affinity and
      tissue distribution. (67)Ga-labeled DOTA-somatostatin analogs were rapidly
      excreted from nontarget tissues, leading to excellent tumor-to-nontarget tissue
      uptake ratios. Of interest for radiotherapeutic application, [(67)Ga]DOTATOC was
      strongly internalized by AR4-2J cells. Furthermore, our results suggest a link
      between the radioligand charge and its kidney retention. The excellent tumor
      selectivity of Ga-DOTA somatostatin analogs together with the different
      applications of Ga in nuclear oncology suggests that Ga-DOTA somatostatin analogs
      will become an important tool in the management of SSTR-positive tumors.

PMID- 11948477
TI  - Somatic mutations in the BRCA2 gene and high frequency of allelic loss of BRCA2
      in sporadic male breast cancer.
AB  - Breast cancer occurs rarely in men and risk factors for the disease include
      germline mutations of the BRCA2 gene. High frequency of allelic loss at the BRCA2
      locus has been reported in sporadic breast tumors, but somatic mutations of BRCA2
      are very rare. Here we report the first case of somatic BRCA2 mutation in male
      breast cancer with demonstrated loss of heterozygosity. We analyzed a series of
      27 archival samples from male breast cancer patients for BRCA2 mutations and loss
      of heterozygosity at BRCA2 locus. The mutation analysis of BRCA2 gene was
      performed using SSCA-HA and sequencing methods. PCR was used to detect LOH at 3
      highly polymorphic microsatellite markers spanning BRCA2 region on 13q by
      comparing the allelic pattern in matched tumor and blood DNA samples. In this
      study LOH at the BRCA2 locus was observed in 82.6% of informative cases,
      confirming previous observations on high frequency of LOH affecting the BRCA2
      region in male breast cancer. We identified 5 somatic BRCA2 mutations in a set of
      23 sporadic male breast cancers (21%). Two silent and 1 missense alterations were
      novel BRCA2 variants. Here we also report first somatic frameshift BRCA2 mutation
      in male breast cancer 8138del5. In 3 tumors with somatic BRCA2 alterations, 1
      missense, 1 silent and frameshift LOH at chromosome 13q12-13 were detected and
      losses involved a wild-type allele of BRCA2 gene.

PMID- 11948478
TI  - VEGF-C induced lymphangiogenesis is associated with lymph node metastasis in
      orthotopic MCF-7 tumors.
AB  - The spread of cancer cells to regional lymph nodes through the lymphatic system
      is the first step in the dissemination of breast cancer. In several human cancers
      including those of the breast and prostate, the expression of vascular
      endothelial growth factor C (VEGF-C) is associated with lymph node metastasis.
      Our study was undertaken to evaluate the effect of VEGF-C on metastasis of poorly
      invasive, estrogen dependent human MCF-7 breast cancer cells. MCF-7 breast cancer
      cells transfected with VEGF-C (MCF-7-VEGF-C) were grown as tumors in the mammary
      fat pads of nude mice implanted with subcutaneous estrogen pellets. Tumor
      lymphangiogenesis and lymph node metastasis were studied immunohistochemically
      using antibodies against lymphatic vessel hyaluronan receptor -1 (LYVE-1), VEGF
      receptor-3 (VEGFR-3), PECAM-1, pan-cytokeratin and estrogen dependent pS2
      protein. Overexpression of VEGF-C in transfected MCF-7 cells stimulated in vivo
      tumor growth in xenotransplanted mice without affecting estrogen responsiveness.
      The resulting tumors metastasized to the regional lymph nodes in 75% (in 6 mice
      out of 8, Experiment I) and in 62% (in 5 mice out of 8, Experiment II) of mice
      bearing orthotopic tumors formed by MCF-7-VEGF-C cells whereas no metastases were
      observed in mice bearing tumors of control vector-transfected MCF-7 cells (MCF-7
      Mock). The density of intratumoral and peritumoral lymphatic vessels was
      increased in tumors derived from MCF-7-VEGF-C cells but not MCF-7-Mock cells.
      Taken together, our results show that VEGF-C overexpression stimulates tumor
      lymphangiogenesis and induces normally poorly metastatic estrogen-dependent MCF-7
      tumors to disseminate to local lymph nodes. These data suggest that VEGF-C has an
      important role in lymph node metastasis of breast cancer even at its hormone
      dependent early stage.

PMID- 11948479
TI  - A case-control study of lung cancer in Karachi, Pakistan.

PMID- 11948484
TI  - Vascular targeting agents enhance chemotherapeutic agent activities in solid
      tumor therapy.
AB  - The utility of combining the vascular targeting agents 5,6-dimethyl-xanthenone-4
      acetic acid (DMXAA) and combretastatin A-4 disodium phosphate (CA4DP) with the
      anticancer drugs cisplatin and cyclophosphamide (CP) was evaluated in
      experimental rodent (KHT sarcoma), human breast (SKBR3) and ovarian (OW-1) tumor
      models. Doses of the vascular targeting agents that led to rapid vascular
      shutdown and subsequent extensive central tumor necrosis were identified.
      Histologic evaluation showed morphologic damage of tumor cells within a few hours
      after treatment, followed by extensive hemorrhagic necrosis and dose-dependent
      neoplastic cell death as a result of prolonged ischemia. Whereas these effects
      were induced by a range of CA4DP doses (10-150 mg/kg), the dose response to DMXAA
      was extremely steep; doses < or = 15 mg/kg were ineffective and doses > or = 20
      mg/kg were toxic. DMXAA also enhanced the tumor cell killing of cisplatin, but
      doses > 15 mg/kg were required. In contrast, CA4DP increased cisplatin-induced
      tumor cell killing at all doses studied. This enhancement of cisplatin efficacy
      was dependent on the sequence and interval between the agents. The greatest
      effects were achieved when the vascular targeting agents were administered 1-3 hr
      after cisplatin. When CA4DP (100 mg/kg) or DMXAA (17.5 mg/kg) were administered 1
      hr after a range of doses of cisplatin or CP, the tumor cell kill was 10-500-fold
      greater than that seen with chemotherapy alone. In addition, the inclusion of the
      antivascular agents did not increase bone marrow stem cell toxicity associated
      with these anticancer drugs, thus giving rise to a therapeutic gain.

PMID- 11948485
TI  - TCR reconstitution in Jurkat reporter cells facilitates the identification of
      novel tumor antigens by cDNA expression cloning.
AB  - The identification of novel tumor antigens is of extreme importance for effective
      immunotherapy against cancer. A major obstacle in this field is the limited life
      span of tumor-specific cytotoxic T lymphocytes (CTLs) in vitro. Therefore we
      searched for a method to isolate the tumor specificity of these CTLs, i.e., their
      T-cell receptors (TCRs) and transfer it to an immortalized T-cell line. For this
      purpose, a TCR-negative Jurkat T-cell line was equipped with a nuclear factor of
      activated T cells (NFAT)-luciferase reporter construct to allow measurement of
      TCR-mediated activation. To establish the feasibility of this tumor-specific TCR
      transduction, we cloned the TCR genes of a known T-cell clone specific for the
      tumor antigen CAMEL (CTL-recognized antigen on melanoma) into a retroviral
      construct. Jurkat reporter cells transduced with this construct, Jrt
      TCRalpha3beta5, were tested for their reactivity against CAMEL-expressing
      melanoma cells, peptide-loaded T2 cells and CAMEL-transfected COS-1 cells. The
      melanoma cell lines were poorly recognized, but peptide-pulsed and -transfected
      cells effectively stimulated NFAT signaling. The activation of TCR(+) Jurkat
      reporter cells was shown to be dependent on the antigen density on the target
      cells and the expression level of the coreceptor CD8 on the Jurkat cells. To
      verify the benefit of this TCR reconstitution method for identification of novel
      antigens, pools of the cDNA library from which CAMEL was originally cloned were
      transfected in COS-1 cells and screened with Jrt-TCRalpha3beta5. Identical cDNA
      pools were found that were positive with these cells and with the CAMEL-specific
      CTL clone. Our results illustrate that TCR-reconstituted Jurkat reporter cells
      are a useful tool in the identification of novel tumor antigens by cDNA
      expression cloning.

PMID- 11948486
TI  - Polycyclic aromatic hydrocarbon-DNA adducts in liver tissues of hepatocellular
      carcinoma patients and controls.
AB  - HCC is a common cancer and HBV and AFB(1) are well-documented, major risk
      factors. Epidemiologic studies have documented that cigarette smoking also
      contributes to the development of HCC. PAHs are ubiquitous environmental
      pollutants and products of incomplete combustion. They are present in both
      mainstream and sidestream cigarette smoke. PAHs are metabolically activated by
      phase I enzymes, including CYP1A1, into electrophilic reactants (diol epoxides),
      which covalently bind to DNA to form adducts. Diol epoxides are also substrates
      for phase II detoxifying enzymes, including GSTM and GSTP. To examine the
      association between PAH-DNA adducts and HCC, adduct levels were determined in
      liver tissue by relative staining intensity with an immunoperoxidase method using
      a polyclonal antiserum against BPDE-modified DNA. Subjects were also genotyped
      for polymorphism in several genes involved in the metabolism of PAH, including
      GSTM1 and GSTP1. Liver tissue was collected from patients with histologically
      confirmed HCC (n = 105) and from non-HCC controls (n = 37). There was a
      significant positive correlation (r = 0.3, p < 0.01) between adducts in tumor and
      adjacent nontumor tissues among HCC cases. The risk of HCC was higher after
      adjustment for age, sex and HBsAg in the group with the highest tertile tissue
      levels of PAH-DNA adducts (mean relative nuclear staining intensity of tumor and
      nontumor tissue > 344) than in the group with the lowest tertile (staining < 241,
      OR = 3.9, 95% CI = 1.0-14.9). Among non-HCC controls, there were no significant
      associations between adduct levels and cigarette smoking, GSTM1 null genotype and
      HBsAg positivity. A strikingly increased HCC risk was observed (OR = 20.3, 95% CI
      = 5.0-81.8) among HBsAg-positive subjects whose PAH-DNA adduct levels were high
      (mean relative nuclear staining intensity of tumor and nontumor tissue > 301,
      median of control tissues) compared to HBsAg-negative subjects who had low PAH
      DNA adduct levels. 4-ABP- and AFB(1)-DNA adducts had been measured previously in
      these same tissues. Subjects with elevated DNA adduct levels of PAH, 4-ABP and
      AFB(1) had a significantly higher HCC risk with an OR of 36.7 (95% CI 7.2-187.2)
      compared to those who had low DNA adduct levels. These results suggest that PAHs
      may play a role in human hepatocarcinogenesis in conjunction with HBsAg carrier
      status, GSTM1 and GSTP1 genotypes and exposure to 4-ABP and AFB(1).

PMID- 11948487
TI  - Expression of p53 and its homologues in primary and recurrent squamous cell
      carcinomas of the head and neck.
AB  - The tumour-suppressor protein p53 belongs to a family that includes 2
      structurally related proteins, p63 and p73. Because of their structural homology,
      it has been hypothesized that both homologues serve as "spare mechanisms" in p53
      mutations to regulate the cell cycle by inducing apoptosis. We investigated the
      mutational and protein expression status of p53 in correlation to its homologues,
      p73 and p63, in primary and recurrent squamous cell carcinomas of the head and
      neck (HNSCC) and corresponding nonneoplastic mucosa. Expression and mutation of
      p53 and its homologues p63 (including the 2 major isotypes TAp63 and DeltaNp63)
      and p73 was examined by direct DNA sequencing and immunohistochemistry in 29
      primary and 39 recurrent (secondary) HNSCCs after microdissection. Our results
      were correlated with pathohistologic stage and grade. p53 mutations were detected
      in 32/68 (47%) carcinomas of 17 patients, with a discordant mutation pattern of
      primary and consecutive tumours in all cases. Positive immunostaining for p63 was
      found in 55/68 (81%) carcinomas of 29 patients. Immunohistochemistry revealed p73
      protein expression in 32/68 (47%) tumours. In normal mucosa, p63 and p73 were
      expressed in 40/68 (59%) and 12/68 (18%) cases, respectively. We failed to detect
      specific mutations of p73 or p63 in primary and recurrent carcinoma of the head
      and neck. p73 and p63 were rarely mutated in HNSCC, but both were expressed in a
      subset of tumours. The lack of correlation between p73/p63 and p53 protein
      expression suggests that neither p73 nor p63 can replace p53 when it is mutated.

PMID- 11948488
TI  - Bcl-X(L) is a chemoresistance factor in human melanoma cells that can be
      inhibited by antisense therapy.
AB  - Malignant melanoma is a tumor that responds poorly to a variety of apoptosis
      inducing treatment modalities, such as chemotherapy. The expression of genes that
      regulate apoptotic cell death plays an important role in determining the
      sensitivity of tumor cells to chemotherapeutic intervention. Bcl-x(L) is an
      antiapoptotic member of the Bcl-2 family and is universally expressed in human
      melanoma. To evaluate the Bcl-x(L) protein as a potential therapeutic target in
      melanoma, the influence of Bcl-x(L) expression levels on the chemoresistance of
      human melanoma cells was investigated. Overexpression of Bcl-x(L) in stably
      transfected human melanoma Mel Juso cells significantly reduced sensitivity to
      cisplatin-induced apoptosis (p < or = 0.05). In a parallel approach, reduction of
      Bcl-x(L) protein by specific AS oligonucleotide (ISIS 16009) treatment enhanced
      the chemosensitivity of Mel Juso cells by 62% compared to cells treated with MM
      control oligonucleotide (ISIS 16967) as well as chemotherapy-induced apoptosis.
      These data suggest that Bcl-x(L) is an important factor contributing to the
      chemoresistance of human melanoma. Reduction of Bcl-x(L) expression by AS
      oligonucleotides provides a rational and promising approach that may help to
      overcome chemoresistance in this malignancy.

PMID- 11948490
TI  - Enzymatic oxidation products of spermine induce greater cytotoxic effects on
      human multidrug-resistant colon carcinoma cells (LoVo) than on their wild-type
      counterparts.
AB  - The occurrence of resistance to cytotoxic agents in tumor cells, associated with
      several phenotypic alterations, is one of the major obstacles to successful
      anticancer chemotherapy. A new strategy to overcome MDR of human cancer cells was
      studied, using BSAO, which generates cytotoxic products from spermine, H(2)O(2)
      and aldehyde(s). The involvement of these products in causing cytotoxicity was
      investigated in both drug-sensitive (LoVo WT) and drug-resistant (LoVo DX) colon
      adenocarcinoma cells. Evaluation of clonogenic cell survival showed that LoVo DX
      cells are more sensitive than LoVo WT cells. Fluorometric assay and treatments
      performed in the presence of catalase demonstrated that the cytotoxicity was due
      mainly to the presence of H(2)O(2). Cytotoxicity was eliminated in the presence
      of both catalase and ALDH. Transmission electron microscopic observations showed
      more pronounced mitochondrial modifications in drug-resistant than in drug
      sensitive cells. Mitochondrial functionality studies performed by flow cytometry
      after JC-1 labeling revealed basal hyperpolarization of the mitochondrial
      membrane in LoVo DX cells. After treatment with BSAO and spermine, earlier and
      higher mitochondrial membrane depolarization was found in LoVo DX cells than in
      drug-sensitive cells. In addition, higher basal ROS production in LoVo DX cells
      than in drug-sensitive cells was detected by flow-cytometric analysis, suggesting
      increased mitochondrial activity in drug-resistant cells. Our results support the
      hypothesis that mitochondrial functionality affects the sensitivity of cells to
      the cytotoxic enzymatic oxidation products of spermine, which might be promising
      anticancer agents, mainly against drug-resistant tumor cells.

PMID- 11948491
TI  - Loss of tumor suppressor protein PTEN during renal carcinogenesis.
AB  - The tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from
      chromosome 10) encodes a dual specific protein and phospholipid phosphatase that
      affects cell proliferation, apoptosis and migration. In our study, we examined
      protein expression of PTEN in renal carcinogenesis. PTEN protein levels were
      examined in 42 clear cell renal cell carcinomas (ccRCC) and oncocytomas as well
      as in the corresponding normal renal tissue of the same patients using Western
      blot analysis. Cellular localization was analyzed by immunohistochemistry. PTEN
      was highly expressed in all investigated normal renal tissue specimens.
      Immunohistochemical analysis showed an almost exclusive staining of proximal
      tubulus epithelial cells known to be precursor cells of ccRCC. Within the
      proximal tubulus cells, PTEN exhibited a membrane predominant immunostaining
      pattern. In ccRCCs PTEN expression was markedly reduced to an average of less
      than 10% compared with normal tissue as evidenced by Western blot analysis (p <
      0.001). The degree of reduction was similar in highly differentiated (G1)
      carcinomas and in less differentiated (G2-G4) carcinomas. These observations were
      reproduced by immunohistochemical studies, which revealed a loss of the
      characteristic membrane predominant immunostaining pattern in ccRCC. In contrast
      to the PTEN positive proximal tubulus epithelial cells, the distal tubulus
      epithelial cells, which are precursor cells of the benign oncocytomas, exhibited
      only a very weak PTEN expression. Compared with the distal tubulus epithelial
      cells, no downregulation of PTEN was seen in oncocytomas. We conclude that PTEN
      expression and PTEN membrane localization are lost during early renal cell
      carcinogenesis and may therefore be a valuable RCC tumor marker.

PMID- 11948489
TI  - C-myc gene expression alone is sufficient to confer resistance to antiestrogen in
      human breast cancer cells.
AB  - C-myc is implicated in the initiation, progression and estrogen response of
      breast cancer. To further investigate the role of c-myc in breast cancer, we have
      developed clonal MCF-7 human breast cancer cell lines harboring a stably
      transfected human c-myc gene, whose expression was stringently controlled by the
      bacterial reverse tetracycline transcription activator protein. The expression of
      the endogenous genomic c-myc gene in MCF-7 cells was abolished by the potent pure
      estrogen antagonist, ICI 182,780. Functional c-Myc protein was identified by both
      Western immunoblotting and by its ability to transactivate a chimeric plasmid
      consisting of E-box sequences upstream of the luciferase reporter gene. One MCF-7
      clone, 35im, was chosen for further characterization. C-myc induction by
      doxycycline was rapid and dose dependent; c-myc mRNA appeared as early as 30 min
      after doxycycline addition and stimulation of c-myc expression required as little
      as 50 ng/ml doxycycline, with c-myc mRNA levels reaching a plateau at 2.5
      microg/ml doxycycline. ICI 182,780 or doxycycline (a tetracycline analog)
      treatment did not alter the mRNA levels of Max, the c-myc binding partner. As in
      wildtype MCF-7 cells, the growth of clone 35im was inhibited by 1 microM or less
      of ICI 182,780 and stimulated by 10 nM to 1 microM 17beta-estradiol. When
      maintained in a complete medium containing 5% normal fetal bovine serum (FBS) and
      ICI 182,780, doxycycline induced cell growth by 400% in an 8-day assay. A similar
      level of growth was achieved with doxycycline treatment in cells that were
      arrested by the use of charcoal-stripped FBS. Doxycycline had no effect on the
      growth of a control MCF-7 clone (18c). Apoptosis, assessed by caspase-dependent
      cleavage of poly(ADP-ribose) polymerase, was unchanged in clone 35im cells after
      treatments with doxycycline or ICI 182,780. The present study demonstrates that c
      myc alone is sufficient to confer antiestrogen resistance in human breast cancer.
      Our novel c-myc-inducible MCF-7 cell model offers a unique opportunity to study
      the diverse actions of the c-myc proto-oncogene in human breast cancer.

PMID- 11948492
TI  - Increased expression of CHK2 in human gastric carcinomas harboring p53 mutations.
AB  - Human Chk1 and Chk2 are DNA damage-activated protein kinases that function as
      downstream mediators of ataxia-telangiectasia mutated (ATM), which is involved in
      G(2)/M cell cycle arrest. To clarify the relation between the expression of
      Chk1/Chk2 and p53 gene status in human gastric carcinomas, we examined expression
      of Chk1, Chk2 and p53 proteins in 87 gastric carcinomas by Western blotting and
      immunohistochemistry. We found a significant correlation between the expression
      levels of Chk1 and p53 proteins in gastric carcinomas (p = 0.016). Significant
      statistical association was also observed between levels of Chk2 and p53 proteins
      (p = 0.00024). To clarify the genetic alterations of p53 in gastric carcinomas,
      we performed PCR-SSCP analysis on 47 gastric carcinomas. Although we found that 5
      of 7 (71%) gastric cancers expressed elevated levels of Chk1 had p53 mutation,
      there was not a statistically significant correlation between expression of Chk1
      and genetic status of p53. We also found that 7 of 11 (78%) gastric carcinomas
      expressed elevated levels of Chk2 had p53 mutation, and this correlation was
      significant (p = 0.0157). We used a highly quantitative 5' nuclease fluorogenic
      RT-PCR method (TaqMan) to analyze the expression of Chk2 mRNA in 22 gastric
      carcinomas. Chk2 mRNA expression was higher in gastric carcinomas with p53
      mutations compared to those harboring wild-type p53. A significant association
      was recognized between the expression of Chk2 mRNA and p53 mutational status (p =
      0.031). Our findings support the hypothesis that expression of Chk2 protein is
      increased in gastric carcinomas with mutant p53. Chk1 and Chk2 may play important
      roles in the checkpoint function in human gastric carcinomas harboring p53
      mutation when their functions are preserved to prevent cell cycle progression.

PMID- 11948493
TI  - Nuclear PTEN expression and clinicopathologic features in a population-based
      series of primary cutaneous melanoma.
AB  - Germline mutations of the PTEN tumor-suppressor gene, on 10q23, cause Cowden
      syndrome, an inherited hamartoma syndrome with a high risk of breast, thyroid and
      endometrial carcinomas and, some suggest, melanoma. To date, most studies which
      strongly implicate PTEN in the etiology of sporadic melanomas have depended on
      cell lines, short-term tumor cultures and noncultured metastatic melanomas. The
      only study which reports PTEN protein expression in melanoma focuses on
      cytoplasmic expression, mainly in metastatic samples. To determine how PTEN
      contributes to the etiology or the progression of primary cutaneous melanoma, we
      examined cytoplasmic and nuclear PTEN expression against clinical and pathologic
      features in a population-based sample of 150 individuals with incident primary
      cutaneous melanoma. Among 92 evaluable samples, 30 had no or decreased
      cytoplasmic PTEN protein expression and the remaining 62 had normal PTEN
      expression. In contrast, 84 tumors had no or decreased nuclear expression and 8
      had normal nuclear PTEN expression. None of the clinical features studied, such
      as Clark's level and Breslow thickness or sun exposure, were associated with
      cytoplasmic PTEN expressional levels. An association with loss of nuclear PTEN
      expression was indicated for anatomical site (p = 0.06) and mitotic index (p =
      0.02). There was also an association for melanomas to either not express nuclear
      PTEN or to express p53 alone, rather than both simultaneously (p = 0.02). In
      contrast with metastatic melanoma, where we have shown previously that almost two
      thirds of tumors have some PTEN inactivation, only one-third of primary melanomas
      had PTEN silencing. This suggests that PTEN inactivation is a late event likely
      related to melanoma progression rather than initiation. Taken together with our
      previous observations in thyroid and islet cell tumors, our data suggest that
      nuclear-cytoplasmic partitioning of PTEN might also play a role in melanoma
      progression.

PMID- 11948494
TI  - Distinct chromosomal imbalances in pleomorphic and in high-grade dedifferentiated
      liposarcomas.
AB  - Using comparative genomic hybridization, DNA copy number changes were studied in
      14 pleomorphic liposarcomas and compared to those detected in high-grade areas of
      9 dedifferentiated liposarcomas. A total of 251 gains and 84 losses were
      detected. The most frequent gains involved subregions of chromosomal arms 12q and
      20q (70% each), 5p (57%), 6q and 9q (52% each), 1q, 7p and 17p (48% each), 1p
      (43%), 6p and 17q (39% each), 20p and 22q (35% each) as well as 7q and 12p (30%
      each). The same subregions were also affected by 30 high level amplifications.
      The most frequent losses were found in subregions of chromosomal arms 13q (35%)
      as well as 11q and 12p (30% each). Overall, gains of chromosomal material were
      more frequent than losses (p < 0.001). There were significant differences in the
      frequency and distribution of recurrent chromosomal imbalances between
      pleomorphic liposarcomas and the dedifferentiated areas of dedifferentiated
      liposarcomas. Gains of chromosomal material detected predominantly in pleomorphic
      liposarcomas involved subbands 5p13-p15 (p < 0.010), 1p21 (p < 0.019), 1q21-q22
      (p < 0.040) and 7q22 (p < 0.049). Conversely, high level amplifications within
      chromosomal subregion 12q13-q21 were only found in the dedifferentiated
      components of dedifferentiated liposarcomas (p < 0.001). Overall, both gains and
      the less pronounced losses of chromosomal material were more frequent in
      pleomorphic than in dedifferentiated liposarcomas (p < 0.001 and p < 0.025,
      respectively). These results show that pleomorphic liposarcomas display a
      considerable number of recurrent chromosomal imbalances that are essentially
      different from those present in high-grade areas of dedifferentiated
      liposarcomas. Therefore, genetic data are considered as a helpful diagnostic
      adjunct for the discrimination between these 2 types of liposarcoma. The overall
      higher frequency of chromosomal imbalances in pleomorphic as compared to
      dedifferentiated liposarcomas could account for the more aggressive biological
      behavior of pleomorphic relative to dedifferentiated liposarcoma types.

PMID- 11948495
TI  - Kinetics of the early recruitment of leukocyte subsets at the sites of tumor
      cells in the lungs: natural killer (NK) cells rapidly attract monocytes but not
      lymphocytes in the surveillance of micrometastasis.
AB  - Early host defense mechanisms play a critical role for the outcome of metastatic
      disease but most of the initial steps of such responses against tumor cells are
      still unknown. Here, the specificity and kinetics of leukocyte subsets in
      response to intravenous inoculation of vital dye labeled Fischer 344 rat
      syngeneic MADB106 tumor cells were monitored in lungs in situ by
      immunohistochemistry and image analysis over a time-period of 6 hr. In comparison
      with sham injections, tumor cell inoculation induces a dynamic sequence of
      rapidly increasing granulocyte (+40% at 5 min), NK and T cell (+60% at 15 min) as
      well as monocyte (+100% at 30 min) numbers in lung tissue. Already within the
      first minutes frequent colocalizations of granulocytes and NK cells with tumor
      targets were found in situ. Within the first hour NK cells selectively kill tumor
      targets, because depletion of NK cells in vivo drastically increases both the
      number of MADB106 cells retained in lungs and the emerging numbers of lung tumor
      colonies. In addition, the tumor-cell-induced increase of monocytes strictly
      depends on the presence of NK cells because NK-depletion completely abrogates the
      time specific response of monocytes. Under NK depleted conditions the tumor
      induced recruitment of CD4(+) T cells is more pronounced suggesting a
      compensatory mechanism. In contrast, B cell numbers progressively decrease within
      hours after cell inoculation. These findings demonstrate that NK and T cells
      mediate the initial steps in the surveillance of lung metastasis. NK cells
      rapidly kill tumor cells and subsequently recruit monocytes in vivo.

PMID- 11948496
TI  - Loss of single HLA class I allospecificities in melanoma cells due to selective
      genomic abbreviations.
AB  - Expression of human leucocyte antigen (HLA) Class I molecules is essential for
      the recognition of malignant melanoma (MM) cells by CD8(+) T lymphocytes. A
      complete or partial loss of HLA Class I molecules is a potent strategy for MM
      cells to escape from immunosurveillance. In 2 out of 55 melanoma cell cultures we
      identified a complete phenotypic loss of HLA allospecificities. Both patients
      have been treated unsuccessfully with HLA-A2 peptides. To identify the reasons
      underlying the loss of single HLA-A allospecificities, we searched for genomic
      alterations at the locus for HLA Class I alpha-chain on chromosome 6 in melanoma
      cell cultures established from 2 selected patients with MM in advanced stage.
      This deficiency was associated with alterations of HLA-A2 gene sequences as
      determined by polymerase chain reaction-sequence specific primers (PCR-SSP).
      Karyotyping revealed a chromosomal loss in Patient 1, whereas melanoma cell
      cultures established from Patient 2 displayed 2 copies of chromosome 6. Loss of
      heterozygosity (LOH) using markers located around position 6p21 was detected in
      both cases. By applying group-specific primer-mixes spanning the 5'-flanking
      region of the HLA-A2 gene locus the relevant region was amplified by PCR and
      subsequent sequencing allowed alignment with the known HLA Class I reference
      sequences. Functional assays using HLA-A2-restricted cytotoxic T-cell clones were
      performed in HLA-A2 deficient MM cultures and revealed a drastically reduced
      susceptibility to CTL lysis in HLA-A2 negative cells. We could document the
      occurrence of selective HLA-A2 deficiencies in cultured advanced-stage melanoma
      metastases and identify their molecular causes as genomic alterations within the
      HLA-A gene locus.

PMID- 11948497
TI  - Cytotoxic T lymphocyte mediated recognition of human pancreatic cancer cells.
AB  - T lymphocytes play an important role in tumor rejection and their response to
      human malignant melanoma has been well documented. In contrast, the existence of
      cytotoxic T lymphocytes (CTL) to pancreatic cancer remains unclear. Tumor
      associated lymphocytes (TAL) and peripheral blood monocytes (PBMC) were isolated
      from pancreatic cancer patients. Tumor-specific CTL were generated from TAL and
      PBMC using solid-phase anti-CD3, low-dose IL-2 (50 IU/ml) and repetitive
      autologous tumor stimulation. The specificity of CTL was tested in standard
      cytotoxicity assays using autologous tumor cells, autologous fibroblasts when
      available, several allogeneic pancreatic tumor cells and the NK-sensitive cell
      line K562. Anti-HLA-Class I MAb, W6/32, was used to demonstrate that tumor
      specific CTL were HLA-Class I restricted. HLA-molecules of human pancreatic
      cancer cells were washed out using acid elution. Eight consecutive,
      histologically confirmed pancreatic cancer specimen as well as peripheral blood
      mononuclear cells were analyzed. CTL were capable of lysing autologous tumor
      cells significantly after 3 stimulations with autologous tumor cells. T cell
      mediated recognition was HLA-Class I restricted as shown by incubation with MAb
      anti-HLA-Class I. In case of HLA-A2 positivity, incubation of tumor cells in
      cytotoxicity assays resulted in significant inhibition. Autologous fibroblasts or
      K562 cells were lysed significantly less. HLA-Class I molecule elution resulted
      in significantly lower recognition of these cells by CTL. These results show for
      the first time in a larger series the possibility of generating CTL in human
      pancreatic cancer. The identification of new tumor associated antigens or tumor
      antigens will be crucial for establishing new treatment strategies.

PMID- 11948498
TI  - Identification and prevalence of CD8(+) T-cell responses directed against Epstein
      Barr virus-encoded latent membrane protein 1 and latent membrane protein 2.
AB  - Epstein-Barr virus (EBV) is associated with several human malignancies that each
      show different viral gene expression profiles. In malignancies such as Hodgkin's
      disease and nasopharyngeal carcinoma only Epstein-Barr nuclear antigen 1 (EBNA1)
      and varying levels of latent membrane proteins 1 and 2 (LMP1 and -2) are
      expressed. Since endogenously expressed EBNA1 is protected from CTL recognition,
      LMP1 and LMP2 are the most likely target antigens for anti-tumor immunotherapy.
      Therefore, we sought to identify in a systematic way CD8(+) T-cell responses
      directed against eptitopes derived from LMP1 and LMP2. Using IFNgamma-ELISPOT
      assays of interferon-gamma release, peripheral blood mononuclear cells (PBMC) of
      healthy donors were screened with peptide panels (15 mer overlapping by 10)
      spanning the LMP1 and LMP2 sequences of the prototype EBV strain B95.8. When
      positive responses were found, CD4(+) or CD8(+) T cells were depleted from donor
      PBMC to determine the origin of the responder population. We detected CD8(+) T
      cell responses to LMP1 in 9/50(18%) donors and to LMP2 in 15/28 (54%) donors. In
      addition to the already described epitopes, 3 new LMP1- and 5 new LMP2-derived
      CD8(+) epitopes were identified. In most donors LMP1- and LMP2-specific CD8(+)
      precursor frequencies were low compared with precursors against immunodominant
      EBV epitopes from latent (EBNA3A, -3B and -3C) and lytic cycle antigens. These
      results demonstrate that CD8(+) memory T cell responses to LMP1 and especially to
      LMP2 do exist in Caucasians, albeit at low levels and could potentially be
      exploited for therapeutic use.

PMID- 11948499
TI  - Independent prognostic significance of HER-2 oncoprotein expression in pN0
      prostate cancer undergoing curative radiotherapy.
AB  - Existing prognostic algorithms for localized prostate cancer (PC) are hampered by
      poor validation for endpoints other than biochemical relapse such as clinical
      disease progression or survival. Therefore, the prognostic relevance of Her-2
      (Her-2/neu, c-erbB2) protein expression in patients undergoing curative
      radiotherapy (RT) was compared to widely accepted prognostic factors such as
      pretreatment prostate-specific antigen (PSA) levels, biopsy Gleason score and T
      category of the primary tumor. Biopsies from 112 homogeneously treated patients
      with T1-4pN0M0 PC were examined by immunohistochemistry and 37% of cases showed
      membrane-bound Her-2 expression in more than 10% of cancer cells. No definite
      membrane staining was seen in normal prostate epithelium. With 25 patients dead
      of PC and a median follow-up of surviving patients of 71 months (range 48-144),
      the prognostic relevance of Her-2 expression was univariately associated with
      adverse outcome in terms of biochemical or clinical progression-free survival
      (B/C-PFS; p = 0.04), clinical progression-free survival (C-PFS; p = 0.02) and
      disease-specific survival (DSS; p = 0.02). In multivariate analysis, Her-2
      expression, T category and Gleason score were independently associated with C
      PFS, whereas only Her-2 expression and Gleason score were associated with DSS.
      Her-2 expression and Gleason score together discriminated 2 groups of patients
      with 5-year DSS of 95% and 79%, respectively (p < 0.001). Pretreatment PSA levels
      were associated only with B/C-PFS but not with C-PFS or DSS. Together the data
      show for the first time that expression of Her-2 is of prognostic relevance in
      localized PC undergoing RT and suggest that analysis for Her-2 may improve
      prognostic algorithms for clinically relevant endpoints other than biochemical
      relapse.

PMID- 11948500
TI  - Lung cancer near an industrial site in Lithuania with major emissions of airway
      irritants.
AB  - To assess the relation between air pollution with airway irritants, including
      sulfuric acid and lung cancer, a case-control study was performed near an
      industry producing sulfuric acid and fertilizers in Kedainiai county, central
      Lithuania. The county had the highest lung cancer rates of the country among men.
      Between 1967 and 1973, the levels of sulfuric acid exceeded 500 microg/m(3)
      within 2 km of the industry and 100 microg/m(3) more than 5 km away. A total of
      277 men who were diagnosed as having lung cancer during 1981-1991 in Kedainiai
      county were included as well as 1,108 population controls. Information on
      residential history since 1960, smoking habits, occupations and workplaces during
      lifetime was obtained from questionnaires mailed to next-of-kin. The relative
      risk of lung cancer associated with living within approximately 5 km from the
      plant was 1.02 (95% CI: 0.76-1.38) compared to those who had never lived in this
      area. No relation with distance or duration of residence was observed.
      Furthermore, workers at the plant did not have an increased lung cancer risk. The
      relative risk of lung cancer associated with smoking was 21.2 (95% CI: 7.51;
      60.1) for current smokers and 14.0 (95% CI: 4.88; 40.3) for exsmokers. The
      duration of smoking, a low age at start and amount of cigarettes smoked daily
      were positively associated with lung cancer risk. Smoking levels appeared more
      pronounced among study controls than in the rest of the country. Our study could
      not confirm earlier evidence of an association between exposure to airway
      irritants, such as sulfuric acid and lung cancer. Smoking is the major
      determinant of the risk of lung cancer in men in Kedainiai county. It is probable
      that higher smoking rates constitute the main reason for the increased lung
      cancer risk among men in this area.

PMID- 11948501
TI  - Detailed low-dose study of 1,1-bis(p-chlorophenyl)-2,2,2- trichloroethane
      carcinogenesis suggests the possibility of a hormetic effect.
AB  - To obtain information on the effects of nongenotoxic carcinogens at low doses for
      human cancer risk assessment, the carcinogenic potential of the organochlorine
      insecticide, 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), in the liver
      was assessed in F344 rats. In experiment 1, 240 male animals, 21 days old, were
      administered 0, 0.5, 1.0, 2.0, 5.0, 20, 100 and 500 ppm DDT in the diet for 16
      weeks. Experiment 2 was conducted to elucidate the carcinogenic potential of DDT
      at lower levels using 180 rats given doses of 0, 0.005, 0.01, 0.1, 0.2 and 0.5
      ppm. The livers of all animals were immunohistochemically examined for expression
      of glutathione S-transferase placental form (GST-P), putative preneoplastic
      lesions. Quantitative values for GST-P-positive foci in the liver were increased
      dose-dependently in rats given 20 ppm DDT and above with statistical significance
      as compared with the concurrent control value. In contrast, doses of 0.005 and
      0.01 ppm were associated with a tendency for decrease below the control value,
      although not significantly. Western blotting analysis show that cytochrome P-450
      3A2 (CYP3A2) protein expression tended to decrease at 0.005 and 0.01 ppm, a good
      correlation being observed with the change in the number of GST-P-positive foci.
      These findings suggest that a DDT hepatocarcinogenicity may show nonlinear
      response, that is, hormetic response at low doses. Furthermore, since CYP3A2
      protein expression appears to be important for the effects of phenobarbital and
      the alpha-isomer of benzene hexachloride, mRNAs for IL-1 receptor type 1 (IL-1R1)
      and TNF-alpha receptor type 1 (TNFR1) whose ligands have roles not only in
      downregulating CYP3A2 expression but also in inducing antiproliferative effect or
      apoptosis in hepatocyte were examined. Increase was observed at low doses of DDT.
      Oxidative stress in liver DNA, assessed in terms of 8-hydroxydeoxyguanosine as a
      marker, was also decreased. These findings suggest that the possible hormetic
      effect that was observed in our detailed low-dose study of DDT carcinogenesis,
      although not statistically significant, may be linked to levels of oxidative
      stress and proinflammatory cytokines.

PMID- 11948502
TI  - Case-control study evaluating the homogeneity and heterogeneity of risk factors
      between sinonasal and nasopharyngeal cancers.
AB  - Sinonasal cancer and nasopharyngeal cancer may share some risk factors because
      both are located within the upper aerodigestive tract. They may also have
      different etiological profiles because of anatomic or pathologic differences.
      However, the similarities and differences in risk factors have rarely been
      studied within the same population. We assessed the risk factor profiles of
      sinonasal and nasopharyngeal cancers, using data from a case-control study. The 2
      case groups consisted of men aged 31-59 and diagnosed pathologically with
      sinonasal cancer (n=70) and nasopharyngeal cancer (n=113), respectively. Controls
      were men without these cancers and selected from the same areas (n=1910).
      Logistic regression analysis showed that smoking was a risk factor for both
      sinonasal [odds ratio (OR)=2.5, 95% confidence interval (CI) 1.1-5.4] and
      nasopharyngeal cancer (OR=1.8, 95%CI 1.1-3.0). However, ever use of barbiturates
      without a prescription (OR=4.9, 95%CI 1.7-13.8), working with or around cutting
      oils on a job (OR=1.9, 95%CI 1.1-3.1) and ever having had sinus infections
      (OR=2.3, 95%CI 1.1-4.6) were associated with nasopharyngeal cancer only. Having
      received blood products other than a transfusion (OR=9.1, 95%CI 2.2-37.4) and
      exposure to a pesticide containing 2,4,5-T (OR=5.9, 95%CI 1.5-23.7) were related
      to sinonasal cancer only. When data analyses were confined to squamous cell type,
      smoking and exposure to chlorophenols were related to squamous cell tumors at
      both sites. However, use of barbiturates and sinus problems other than infection
      only increased the risk of nasopharyngeal carcinoma. Our study suggests that
      except for smoking and chlorophenol exposure, which are associated with both
      sites, the risk factor profiles may differ between sinonasal and nasopharyngeal
      cancers.

PMID- 11948503
TI  - Circulating enterolactone and prostate cancer risk: a Nordic nested case-control
      study.
AB  - Enterolactone, a phytoestrogen belonging to the class of lignans, is produced by
      the intestinal microflora from precursors in plant foods and has been implicated
      in protection against cancer. We study the effect of enterolactone on the risk of
      a subsequent diagnosis of prostate cancer. We conducted a longitudinal, nested
      case-control study by linkage of 3 biobanks to the cancer registries in Finland,
      Norway and Sweden, respectively. Enterolactone concentrations were measured by
      time-resolved fluoroimmunoassay in serum from 794 men who had a diagnosis of
      prostate cancer at a mean follow-up time of 14.2 years after blood collection and
      among 2,550 control men matched within each cohort for age (+/-2 years), date of
      blood collection (+/-2 months) and county. The median enterolactone
      concentrations did not differ between case and control subjects in the full study
      group (8.4 nmol/L [25th-75th percentile = 4.5-15.0] vs. 8.5 nmol/L [25th-75th
      percentile = 4.3-15.9]), nor in the national groups. Odds ratios of prostate
      cancer risk estimated by conditional logistic regression for increasing
      concentrations of enterolactone in quartiles in the full study group were 1.00
      (referent), 1.21 (95% confidence interval [CI] = 0.96-1.52), 1.16 (95% CI = 0.91
      1.47) and 1.08 (95% CI = 0.83-1.39). The OR estimate for the highest vs. the
      lowest quartile of enterolactone in separate analyses of the Norwegian, Finnish
      and Swedish cohort was 1.21 (95% CI = 0.91-1.60), 1.02 (95% CI = 0.59-1.76) and
      0.87 (95% CI = 0.45-1.67), respectively. No support for the hypothesis that high
      circulating enterolactone is protective against prostate cancer was found.

PMID- 11948504
TI  - Intracellular targeting therapy of cisplatin-encapsulated transferrin
      polyethylene glycol liposome on peritoneal dissemination of gastric cancer.
AB  - Peritoneal dissemination in gastric cancer is a common fatal clinical condition
      with few effective therapies available. We studied the therapeutic effect of a
      tumor-targeting drug delivery system that uses cisplatin-encapsulated and Tf
      conjugated PEG liposomes (Tf-PEG liposomes) in nude mice with peritoneal
      dissemination of human gastric cancer cells. Small unilamellar Tf-PEG, PEG or
      DSPC/CH liposomes (bare liposomes) encapsulating cisplatin were prepared by
      reverse-phase evaporation followed by extrusion. Electron microscopic studies
      revealed that Tf-PEG liposomes were internalized into tumor cells by receptor
      mediated endocytosis. To examine the biodistribution of each liposome and
      cisplatin level, nude mice were inoculated i.p. with 10(7) MKN45P human gastric
      tumor cells. On the fourth day after tumor inoculation, (3)H-CHE-labeled and
      cisplatin-encapsulated Tf-PEG, PEG or bare liposome were inoculated i.p. The Tf
      PEG liposome-administered group maintained high liposome and cisplatin levels in
      ascites and showed a prolonged residence time in the peripheral circulation.
      Uptake of Tf-PEG liposomes into the liver and spleen was significantly lower than
      that of bare liposomes. Uptake of Tf-PEG liposomes in disseminated tumor cells of
      ascites and the greater omentum was significantly higher than that of PEG or bare
      liposomes and a significant increase in cisplatin levels was observed in these
      tumor cells. Mice receiving Tf-PEG liposomes 1 and 4 days after the day of tumor
      inoculation showed significantly higher survival rates compared with those
      receiving PEG liposomes without Tf, bare liposomes or free cisplatin solution.
      These results suggest that cisplatin-encapsulated Tf-PEG liposomes may be useful
      as a new intracellular targeting carrier for treatment of gastric cancer with
      peritoneal dissemination.

PMID- 11948506
TI  - Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of
      human melanoma xenografts.
AB  - Interferon-inducible protein 10 (IP-10) is an immunomodulatory chemokine recently
      recognized to have potent antiangiogenic activity in vivo. Due to difficulties in
      the stability, manufacture and chronic administration of recombinant forms of
      endogenous antiangiogenic proteins, antiangiogenic gene therapy has emerged as a
      promising new form of cancer treatment. We retrovirally transduced A375 human
      melanoma cells with the human IP-10 gene and injected cells subcutaneously into
      nude mice. IP-10-transduced cells also were mixed with null-transduced cells in
      varying proportions before injection. In vivo growth of IP-10-transduced melanoma
      cells was markedly diminished compared to parental or null-transduced cells (p =
      0.0002, Kruskal-Wallis test). This growth inhibition was associated with a marked
      reduction in microvessel density. The degree of growth inhibition of tumors
      following injection of a mixed population of null- and IP-10-transduced cells was
      directly associated with the fraction of IP-10-transduced cells present. We
      conclude that retroviral transduction of human melanoma cells with the IP-10 gene
      leads to sufficient protein secretion to inhibit angiogenesis and tumor growth.
      These findings suggest that IP-10 gene therapy might be an effective therapy in
      patients with cancer.

PMID- 11948505
TI  - Antibody-guided enzyme therapy of cancer producing cyanide results in necrosis of
      targeted cells.
AB  - A number of enzyme/prodrug activation approaches for the treatment of cancer have
      been reported to date with varying success. We describe progress in the
      development of a system based on a beta-glucosidase enzyme in combination with a
      naturally occurring "prodrug," the sugar linamarin, which releases the cytotoxin
      cyanide. A recombinant fusion protein, composed of an scFv (MFE-23) reactive
      against carcinoembryonic antigen (CEA) and a plant-derived beta-glucosidase
      (linamarase), was produced and its cytotoxic potential was investigated. The
      fusion protein was expressed in a supersecretory mutant strain of Saccharomyces
      cerevisiae and purified by affinity chromatography. Extensive functional in vitro
      characterisation of the fusion protein showed that it retained antigen binding
      activity but that its catalytic activity was impaired, a problem not related to
      its fusion with the scFv. Nevertheless, we demonstrated complete tumour cell
      killing at doses of prodrug that are completely nontoxic to nontargeted cells.
      Preliminary in vivo characterisation showed that extensive glycosylation of the
      fusion protein caused its rapid clearance through the hepatic route.
      Aggregational properties also led to poor pharmacokinetics. Furthermore, we
      present some data analysing the mode of cell death resulting from exposure to
      this system. Enzymic catalysis of the substrate generates cyanide, a metabolic
      poison that asphyxiates cells and leads them to a necrotic-like cell death. This
      system has been called antibody-guided enzyme nitrile therapy (AGENT).

PMID- 11948507
TI  - False cell lines.

PMID- 11948509
TI  - Evaluation of nanostructured carbonated hydroxyapatite coatings formed by a
      hybrid process of plasma spraying and hydrothermal synthesis.
AB  - Carbonated hydroxyapatite (CHA) coatings on a titanium alloy were prepared by
      hydrothermal synthesis of precursors plasma-sprayed with brushite as a raw
      powder. The structures, residual stresses, and bond strengths of the precursors
      and CHA coatings were investigated. The results showed that the sprayed
      precursors consisted of beta-Ca(2)P(2)O(7), alpha-Ca(3)(PO(4))(2), and CaHPO(4),
      whereas the CHA coatings exhibited a unique phase construction, nanostructured
      and needle-like crystals, and a fairly low tensile residual stress. The bond
      strength of a CHA coating 200 microm thick was 15 MPa, equivalent to that of a
      plasma-sprayed hydroxyapatite (HA) coating. The evaluation of the CHA coatings
      was performed together with that of plasma-sprayed HA coatings immersed in
      distilled water. The dissolution and bond-strength degradation of the CHA
      coatings were much lower than those of the plasma-sprayed HA coatings.

PMID- 11948511
TI  - Effect of grooved titanium substratum on human osteoblastic cell growth.
AB  - Various surface treatments have been developed to increase the clinical
      performance of titanium-based implants. Many in vitro tests have been carried out
      on substrates with varied surface topography for a complete understanding of
      osteoblasts. In previous research, we made the observation that surface roughness
      must be taken into account, not only in terms of amplitude but also in terms of
      organization. In this study, we tested the adhesion and proliferation of human
      primary osteoblasts on grooved titanium surfaces with various amplitudes and
      organizations of topography. The roughness was described at a scale above (macro
      roughness) or below (micro-roughness) the cell size. We observed better
      orientation and proliferation of human osteoblasts on surfaces with a micro
      roughness characterized by a lower Order (parameter describing the organization
      of topography) and by a higher Ra and Rz (parameters describing the amplitude of
      topography). It appears that cultured human osteoblasts prefer surfaces with
      relatively high micro-roughness amplitude and with a low level of repeatability.

PMID- 11948510
TI  - Morphologic and functional evaluation of peripheral nerve fibers regenerated
      through polyimide sieve electrodes over long-term implantation.
AB  - We evaluated by morphologic and functional analysis the regeneration of
      peripheral nerve fibers through polyimide regenerative-type electrodes over long
      term implantation. Polyimide sieve electrodes were placed in silicone chambers
      and implanted between the severed ends of the sciatic nerve in rats. The sieve
      part had 281 round via holes of 40 microm in diameter, with nine integrated
      recording-stimulating electrodes arranged around the via holes. The degree of
      axonal regeneration was examined at 2, 7, and 12 months postimplantation (mpi).
      Regeneration was successful in 12 of the 13 animals implanted. Reinnervation of
      distal muscle and nerves increased with time, reaching a plateau about 7 mpi. The
      number of myelinated fibers increased from 2 to 7 months, at which time it was
      similar to control values. With time the myelinated fibers matured, with
      significant increases in axon diameter and myelin thickness. Only 0.6% of the
      regenerated axons showed evidence of compression near the implanted electrode.
      The majority of the myelinated fibers that crossed the via holes and had been
      regenerated through the distal nerve had a normal appearance. Sieve electrodes
      were useful for nerve stimulation at postimplantation. Stimulation through
      different active electrodes excited nerve bundles, evoking compound muscle action
      potentials of varying shape and amplitude, indicative of selective axonal
      stimulation.

PMID- 11948512
TI  - Increase in gap-junctional intercellular communications (GJIC) of normal human
      dermal fibroblasts (NHDF) on surfaces coated with high-molecular-weight
      hyaluronic acid (HMW HA).
AB  - Normal human dermal fibroblast (NHDF) cells were used to detect differences in
      gap-junctional intercellular communication (GJIC) by hyaluronic acid (HA), a
      linear polymer built from repeating disaccharide units that consist of N-acetyl-D
      glucosamine (GlcNa) and D-glucuronic acid (GlcA) linked by a beta 1-4 glycosidic
      bond. The NHDF cells were cultured with different molecular weights (MW) of HA
      for 4 days. The rates of cell attachment in dishes coated with high-molecular
      weight (HMW; 310 kDa or 800 kDa) HA at 2 mg/dish were significantly reduced at an
      early time point compared with low-molecular-weight (LMW; 4.8 kDa or 48 kDa) HA
      with the same coating amounts. HA-coated surfaces were observed by atomic force
      microscopy (AFM) under air and showed that HA molecules ran parallel in the dish
      coated with LMW HA and had an aggregated island structure in the dish coated with
      HMW HA surfaces. The cell functions of GJIC were assayed by a scrape-loading dye
      transfer (SLDT) method using a dye solution of Lucifer yellow. Promotion of the
      dye transfer was clearly obtained in the cell monolayer grown on the surface
      coated with HMW HA. These results suggest that HMW HA promotes the function of
      GJIC in NHDF cells. In contrast, when HMW HA was added to the monolayer of NHDF
      cells, the functions of GJIC clearly were lowered in comparison with the cells
      grown in the control dish or with those grown on the surface of HMW HA. Therefore
      it is concluded that the MW size of HA and its application method are important
      factors for generating biocompatible tissue-engineered products because of the
      manner in which the GJIC participates in cell differentiation and cell growth
      rate.

PMID- 11948514
TI  - Mechanical properties and osteoconductivity of new bioactive composites
      consisting of partially crystallized glass beads and poly(methyl methacrylate).
AB  - New bioactive composites consisting of partially crystallized glass beads as
      inorganic fillers and poly(methyl methacrylate) (PMMA) as an organic matrix were
      developed. Two kinds of partially crystallized glass beads, designated Cry820 and
      Cry850, were newly prepared by the heating of MgO-CaO-SiO(2)-P(2)O(5) glass at
      820 and 850 degrees C, respectively. The glass beads were mixed with PMMA to form
      two new composites designated Cry820C and Cry850C, respectively. The goal of this
      study was to produce a highly osteoconductive and mechanically strong composite
      cement with these new fillers. A previously reported composite cement designated
      AWC, which was composed of apatite- and wollastonite-containing glass ceramic (AW
      GC) as a powder filler and the same PMMA polymer used in the new composites, was
      used as a reference material. The quantity of filler added to each composite was
      70 wt %. The bending strength of Cry820C was significantly higher than that of
      Cry850C. Composites were packed into intramedullary canals of rat tibiae to
      evaluate their osteoconductivity, as determined by an affinity index. The
      affinity index, which equaled the length of bone in direct contact with the
      composite surface expressed as a percentage of the total length of the composite
      surface, was calculated for each composite. The rats were euthanized at 4, 8, and
      25 weeks after implantation. At each time interval studied, Cry820C showed a
      significantly higher affinity index than AWC up to 25 weeks after implantation.
      Cry850C showed a significantly higher affinity index than AWC up to 8 weeks and a
      higher affinity index than AWC at 25 weeks, although the difference was not
      significant. The values for each composite increased significantly with time up
      to 25 weeks. Our study revealed that the higher osteoconductivity of the new
      composites was due to the larger quantity of the glassy phase of the crystallized
      glass beads at the composite surface and the lower solubility of the PMMA powder
      to methyl methacrylate monomer. In addition, the spherical shape of the
      crystallized glass beads gave the new composites strong enough mechanical
      properties to be useful under weight-bearing conditions. The new composites show
      promise as alternatives, with improved properties, to conventional PMMA bone
      cement.

PMID- 11948513
TI  - Biocompatibility assessment of silicone oil and perfluorocarbon liquids used in
      retinal reattachment surgery in rat retinal cultures.
AB  - The effects of silicone oil and perfluorocarbon liquids used in retinal
      reattachment surgery were studied in vitro using rat retinal cultures seeded on
      microporous inserts. These inserts allow the cell layer to be in contact with the
      material to be tested on the apical side and with the nutrient medium on the
      basal side. The materials tested were silicone oil, the perfluorocarbons
      perfluorophenanthrene and perfluoroctane, and hydroxypropylmethylcellulose.
      Perfluorophenanthrene, the heaviest of the compounds, induced a very precocious
      detachment of the cell layer. All the other tested biomaterials were compatible
      with cell survival and did not alter the structural organization of the retinal
      cultures, as revealed by scanning electron microscopy. By immunocytochemical
      techniques we evaluated the cell composition and the differentiation state of
      each of the cultures. In both control and treated samples, neuronal cells were
      well preserved. The expression of microtubule-associated protein 2, a marker of
      differentiated neuronal cytoskeleton, was not affected. Amacrine neurons,
      immunolabeled for gamma-aminobutyric acid, still were detectable after treatment.
      Synapses, marked by immunoreactivity for synapthophysin, were equally preserved.
      Vimentin-positive glial cells did not show modifications. The apoptotic rate, as
      determined by the terminal transferase-mediated dUTP-biotin nick end-labeling
      assay, was similar in treated and control samples. The results confirm that the
      use of biomaterials with a specific gravity close to intraocular fluids is
      compatible with retinal cell survival and differentiation in vitro.

PMID- 11948515
TI  - Theoretical analysis of adsorption thermodynamics for hydrophobic peptide
      residues on SAM surfaces of varying functionality.
AB  - At a fundamental level, protein adsorption to a synthetic surface must be
      strongly influenced by the interaction between the peptide residues presented by
      the protein's surface (primary protein structure) and the functional groups
      presented by the synthetic surface. In this study, semi-empirical molecular
      modeling was used along with experimental wetting data to theoretically approach
      protein adsorption at this primary structural level. Changes in enthalpy,
      entropy, and Gibbs free energy were calculated as a function of residue-surface
      separation distance for the adsorption of individual hydrophobic peptide residues
      (valine, leucine, phenylalanine) on alkanethiol self-assembled monolayers on gold
      [Au-S(CH(2))(15)-X; X = CH(3), OH, NH(3)(+), COO(-)]. The results predict that
      the adsorption of each type of hydrophobic residue is energetically favorable and
      entropy dominated on a methyl-terminated hydrophobic surface, energetically
      unfavorable and enthalpy dominated on a hydroxyl-terminated neutral hydrophilic
      surface, and very slightly favorable to unfavorable and enthalpy dominated on
      charged surfaces. These theoretical results provide a basis for understanding
      some of the fundamental effects governing protein adsorption to synthetic
      surfaces. This level of understanding is needed for the proactive design of
      surfaces to control protein adsorption and subsequent cellular response for both
      implant and tissue engineering applications.

PMID- 11948516
TI  - Manipulation of bacterial adhesion and proliferation by surface charges of
      electrically polarized hydroxyapatite.
AB  - The manipulation of bacterial adhesion and proliferation by surface charges built
      onto the surfaces of electrically polarized bioceramic hydroxyapatite (HAp) was
      investigated. The gram-positive bacteria Staphylococcus aureus (S. aureus) and
      the gram-negative bacteria Escherichia coli (E. coli) were cultivated on
      negatively charged, positively charged, and non-charged HAp surfaces (denoted as
      N-, P-, and 0-surface, respectively). The electrostatic force caused by the
      surface charges experimentally was proven to affect both adhesion and
      proliferation. Compared with the 0-surface of HAp ceramics over a 3-h
      cultivation, the population of adhered bacteria rapidly multiplied on the N
      surface whereas it multiplied quite slowly on the P-surface. Compared with the 0
      surface over a cultivation period of 12 to 72 h, the proliferation rate of the
      bacterial cell density per colony was accelerated on the N-surface and
      decelerated on the P-surface. The above results are attributed (1) to the
      electrostatic interaction between the cell surfaces and the charged surfaces of
      the polarized HAp, (2) to the stimulus of the electrostatic force for bacterial
      cells, and (3) to the concentration of the nutrient for the bacteria.

PMID- 11948517
TI  - Composites consisting of poly(methyl methacrylate) and alumina powder: an
      evaluation of their mechanical and biological properties.
AB  - We developed new composites consisting of comparatively high molecular weight
      poly(methyl methacrylate) (hPMMA) and delta-alumina powder or alpha-alumina
      powder (designated delta-APC and alpha-APC, respectively) that allowed direct
      bone formation on their surfaces in vivo. delta-Alumina powder was manufactured
      by the fusing and quenching of pulverized alumina powder. It was composed mainly
      of delta-crystal phases of alumina. The purpose of this study was to evaluate the
      static mechanical properties and biological properties of these composites. The
      hPMMA itself was used as a reference material. The bending strength and Young's
      modulus of both delta-APC and alpha-APC were significantly higher than those of
      hPMMA, and the alumina composites are believed to be strong enough for use under
      weight-bearing conditions. The three types of composites were packed into the
      intramedullary canals of rat tibiae to evaluate osteoconductivity, as determined
      by an affinity index. Rats were sacrificed 4 and 8 weeks after surgery. The
      affinity index, equal to the length of bone in direct contact with the composite
      surface and expressed as a percentage of the total length of the composite
      surface, was calculated for each composite at each interval. Histologically, new
      bone had formed along the surfaces of both delta-APC and alpha-APC within 4
      weeks. The affinity indices for both delta-APC and alpha-APC increased
      significantly with time up to 8 weeks. At 8 weeks, the affinity index for delta
      APC was significantly higher than the indices for alpha-APC and hPMMA. This study
      revealed that the excellent osteoconductivity of delta-APC was due to the delta
      crystal phases of alumina and the high molecular weight of hPMMA. delta-APC shows
      promise as a base for developing a highly osteoconductive and mechanically strong
      biomaterial.

PMID- 11948518
TI  - Biodegradable polyurethanes for implants. II. In vitro degradation and
      calcification of materials from poly(epsilon-caprolactone)-poly(ethylene oxide)
      diols and various chain extenders.
AB  - Linear, biodegradable, aliphatic polyurethanes with various degrees of
      hydrophilicity were synthesized in bulk at 50-100 degrees C. The ratios between
      the hydrophilic and hydrophobic segments were 0:100, 30:70, 40:60, 50:50, and
      70:30, respectively. The hydrophilic segment consisted of poly(ethylene oxide)
      (PEO) diol (molecular weight = 600 or 2000) or the poly(ethylene-propylene
      ethylene oxide) (PEO-PPO-PEO) diol Pluronic F-68 (molecular weight = 8000). The
      hydrophobic segment was made of poly(epsilon-caprolactone) diol (molecular weight
      = 530, 1250, or 2000). The chain extenders were 1,4-butane diol and 2-amino-1
      butanol. The diisocyanate was aliphatic hexamethylene diisocyanate. The polymers
      absorbed water in an amount that increased with the increasing content of the PEO
      segment in the polymer chain. The total amount of absorbed water did not exceed
      2% for the poly(ester urethane)s and was as high as 212% for some poly(ester
      ether urethane)s that behaved in water like hydrogels. The polymers were
      subjected to in vitro degradation at 37 +/- 0.1 degrees C in phosphate buffer
      solutions for up to 76 weeks. The poly(ester urethane)s showed 1-2% mass loss at
      48 weeks and 1.1-3.8% mass loss at 76 weeks. The poly(ester ether urethane)s
      manifested 1.6-76% mass loss at 48 weeks and 1.6-96% mass loss at 76 weeks. The
      increasing content and molecular weight of the PEO segment enhanced the rate of
      mass loss. Similar relations were also observed for polyurethanes from PEO-PPO
      PEO (Pluronic) diols. Materials obtained with 2-amino-1-butanol as the chain
      extender degraded at a slower rate than similar materials synthesized with 1,4
      butane diol. All the materials already manifested a progressive decrease in the
      molecular weight in the first month of in vitro aging. The rate of molecular
      weight loss was higher for poly(ester ether urethane)s than for poly(ester
      urethane)s. For poly(ester ether urethane)s, the rate of molecular weight loss
      was higher for materials containing Pluronic than for those containing PEO
      segments. All polymers calcified in vitro. The susceptibility to calcification
      increased with material hydrophilicity. The progressive deposition of calcium
      salt on the film surfaces resulted in the formation of large crystal aggregates,
      the structure of which depended on the chemical composition of the calcified
      material. Needle-like aggregates, resembling brushite, formed on the hydrophobic
      polyurethane, and plate-like crystals formed on the highly hydrophilic material.
      The calcium-to-phosphorus atomic ratio of the crystals growing on the samples was
      dependent on the chemical composition of the material and varied from 0.94 to
      1.55.

PMID- 11948519
TI  - Fibrin as an alternative biopolymer to type-I collagen for the fabrication of a
      media equivalent.
AB  - We report here on studies examining the use of fibrin as an alternative to
      collagen for the entrapment of neonatal aortic rat smooth muscle cells (SMCs) in
      the fabrication of media equivalents. The studies show increased collagen
      production by fibroblasts entrapped in fibrin, which suggests that fibrin may be
      used in the fabrication of tissue equivalents to promote increased protein
      synthesis and remodeling. However, one of the challenges of working with fibrin
      is the rapid degradation by SMCs. This degradation was effectively inhibited with
      the addition of epsilon-aminocaproic acid (EACA) to the culture medium in
      concentrations ranging from 0.25 to 1 mg/mL. We also present results showing that
      fibrin stimulates collagen production by SMCs. SMCs in fibrin produced 3.2 and
      4.9 times the amount of collagen produced by SMCs in collagen when supplemented
      with 1 and 0.25 mg/mL EACA, respectively. More than half of the collagen produced
      appeared in the medium rather than the matrix. The collagen in the medium
      appeared to be processed beyond the proform and may be in an aggregate form. In
      addition, the presence of type-III collagen or a type-I trimer was indicated by
      the results of an analysis of the medium by autoradiography.

PMID- 11948520
TI  - Electrospun nanofibrous structure: a novel scaffold for tissue engineering.
AB  - The architecture of an engineered tissue substitute plays an important role in
      modulating tissue growth. A novel poly(D,L-lactide-co-glycolide) (PLGA) structure
      with a unique architecture produced by an electrospinning process has been
      developed for tissue-engineering applications. Electrospinning is a process
      whereby ultra-fine fibers are formed in a high-voltage electrostatic field. The
      electrospun structure, composed of PLGA fibers ranging from 500 to 800 nm in
      diameter, features a morphologic similarity to the extracellular matrix (ECM) of
      natural tissue, which is characterized by a wide range of pore diameter
      distribution, high porosity, and effective mechanical properties. Such a
      structure meets the essential design criteria of an ideal engineered scaffold.
      The favorable cell-matrix interaction within the cellular construct supports the
      active biocompatibility of the structure. The electrospun nanofibrous structure
      is capable of supporting cell attachment and proliferation. Cells seeded on this
      structure tend to maintain phenotypic shape and guided growth according to
      nanofiber orientation. This novel biodegradable scaffold has potential
      applications for tissue engineering based upon its unique architecture, which
      acts to support and guide cell growth.

PMID- 11948521
TI  - Adsorption of proteins from infant and adult plasma to biomaterial surfaces.
AB  - The hemostatic mechanism of the newborn is immature. In general, the clotting
      times in screening tests are prolonged, the coagulation factors are low, and the
      coagulation inhibitors (with the exception of alpha-2-macroglobulin) are low.
      Recognizing that many of the proteins present in infant plasma are at low levels,
      it is of interest to determine if, following exposure to artificial surfaces, the
      profile of adsorbed proteins is different for infant versus adult plasma. The
      question of whether differences in protein profiles could lead to differences in
      thromboembolic episodes associated with the use of central venous catheters (or
      other blood-contacting devices) in infant versus adult subjects also is relevant.
      To address these issues, the adsorption of proteins from pooled infant plasma and
      pooled normal adult plasma to three different polymer surfaces (polyvinyl
      chloride, PVC; polymethyl methacrylate, PMMA; and polyethylene oxide-modified
      polyurethane, PEO-PU) was studied using SDS-PAGE and immunoblotting techniques.
      The total amount of protein adsorbed to each surface also was determined. It was
      found that the PMMA and PVC surfaces adsorbed considerably more protein than the
      PEO-PU surface. Furthermore, the amount of protein adsorbed to the PMMA and PVC
      surfaces from infant plasma was significantly less than that adsorbed from adult
      plasma. No such difference was seen for the protein-repellent PEO-PU surface. The
      immunoblot responses of proteins bound to the PMMA and PVC surfaces from infant
      plasma were, in general, weaker than those bound from adult plasma. It is likely
      that these differences were due to decreased protein levels in infant plasma.

PMID- 11948523
TI  - The porosity dependence of the dielectric constant for sintered hydroxyapatite.
AB  - Hydroxyapatite (HAp) is the major mineral constituent of bone, and as such, the
      dielectric properties of HAp are of interest because electromagnetic fields have
      been shown to accelerate healing in bone fractures. In addition, an interest in
      the dielectric properties of HAp stems from the suggestion that electrically
      insulating HAp coatings might be used on implantable devices. In this study, the
      dielectric constant of polycrystalline hexagonal HAp was measured at nine
      different frequencies, from 45 kHz to 7.3 MHz for relative porosities ranging
      from 0.05 to 0.42. At a fixed frequency, the decrease in k as a function of
      increasing porosity is described well by an exponential function of porosity such
      that k = k(0)exp(-bP), where k(0) is the dielectric constant at zero porosity and
      b is a constant. In addition, the entire data set of 108 data points
      (representing the 12 specimens of differing porosity measured at each of the nine
      frequencies) was fit to a candidate function formed from the product k(0)exp(-bP)
      and a simple expression relating frequency to the dielectric constant. The
      candidate function fit the data relatively well, with a coefficient of
      determination of 0.91.

PMID- 11948522
TI  - In vitro characterization and in vivo properties of a carbonated apatite bone
      cement.
AB  - This study evaluated the in vivo behavior of an injectable calcium phosphate bone
      cement implanted in bone defects at the distal end of rabbit femora. After 3
      weeks, samples were harvested and processed for undecalcified sectioning.
      Scanning electron microscopy, transmission electron microscopy, and Fourier
      transform infrared microspectroscopy showed direct contact of bone and cement
      without soft tissue interposition, biocompatibility, and bioactivity with
      osteoconductive properties.

PMID- 11948524
TI  - Biodegradation of carbonate apatite/collagen composite membrane and its
      controlled release of carbonate apatite.
AB  - The aim of this study was to investigate the biodegradation of carbonate apatite
      (CO(3)Ap)/collagen composite membrane as a new guided tissue regeneration
      membrane in vivo and to estimate its controlled release of CO(3)Ap in vitro. To
      control the biodegradation of the guided tissue regeneration membrane and to
      promote hard tissue regeneration in the periodontal region, we added CO(3)Ap into
      the collagen membrane. To investigate the biodegradation of CO(3)Ap/collagen
      composite membranes, the prepared membranes (CO(3)Ap:0, 10 wt %) were cut into 5
      x 5 x 0.1 mm and subcutaneously implanted into the backside of male rats under
      general anesthesia. The explanted membranes were investigated histologically. To
      estimate their controlled release of CO(3)Ap in vitro, the membranes (CO(3)Ap 0
      10 wt %, 5 x 5 x 0.1 mm) were immersed into collagenase solution and compulsorily
      dissolved for 48 h. Histological results suggested that the membrane had a good
      biocompatibility and the biodegradable period was shortened with the presence of
      CO(3)Ap. In the solubility experiments of the membrane, eluted Ca concentrations
      gradually increased with total dependence on the dissolution of the collagen
      membrane. Our study demonstrated that the biodegradation time can be controlled
      by CO(3)Ap contents in the membrane and CO(3)Ap could be released from the
      membrane with the biodegradation period.

PMID- 11948525
TI  - Viability, adhesion, and bone phenotype of osteoblast-like cells on
      polyelectrolyte multilayer films.
AB  - The aim of this study was to develop new biocompatible coatings for bone implants
      by the alternating deposition of oppositely charged polyelectrolytes.
      Polyelectrolyte films were built up with different terminating layers on which
      SaOS-2 osteoblast-like cells and human periodontal ligament (PDL) cells were
      grown. The terminating layer was made of one of the following polyelectrolytes:
      poly(ethylene imine) (PEI), poly(sodium 4-styrenesulfonate) (PSS),
      poly(allylamine hydrochloride) (PAH), poly(L-glutamic acid) (PGA), or poly(L
      lysine) (PLL). Cell adherence, viability, stability of osteoblast phenotype, and
      inflammatory response were studied. Adherence and viability were good on all
      terminating layers except the PEI-terminating layer, which was cytotoxic.
      Maintenance of osteoblast phenotype marker expression was observed on PSS- and
      PGA-terminating films for both cell types, whereas downregulation, associated
      with the induction of Interleukin-8 (IL-8) secretion, was detected on PEI and PAH
      for both cell types and on PLL for PDL cells. These results suggested a good
      biocompatibility of PSS- and PGA-ending films for PDL cells and of PSS-, PGA-,
      and PLL-terminating films for SaOS-2 cells. As a result, polyelectrolyte
      multilayer films could emerge as new alternatives for implant coatings.

PMID- 11948527
TI  - Stress influence on interface in plasma-sprayed hydroxyapatite coatings on
      titanium alloy.
AB  - During clinical use of hydroxyapatite-coated implants, mechanical stresses are
      added to pre-existing residual stresses. The magnitude of these stresses affects
      the coating's performance. In this work we studied, by neutron diffraction and
      conventional X-ray diffraction methods, the macrostresses induced by a plasma
      spraying process in the coating and at the interface. Neutron diffraction is one
      of the most suitable techniques for studying the strain distribution in a bulk
      material. X-ray diffraction was used to determine residual stress in the
      hydroxyapatite coating. Using a neutron diffraction method at the nearest point
      to the interface, we saw no real difference between the stress observed on coated
      and that on non-coated samples. With the X-ray diffraction method, it appeared
      that the stress level was compressive on every sample. The major advantage of the
      neutron diffraction method is that measurements can be made on a thick coating in
      a nondestructive way. The disadvantage is the large-gauge volume that we had to
      use because of the relatively low intensity of the neutron beam. Polishing is
      necessary for measurements inside the material when using the X-ray method. This
      destructive method may alter the stress field of the deposit.

PMID- 11948526
TI  - Engineering vascular networks in porous polymer matrices.
AB  - Enhanced vascularization is critical to the treatment of ischemic tissues and the
      engineering of new tissues and organs. We have investigated whether sustained and
      localized delivery of vascular endothelial growth factor (VEGF) combined with
      transplantation of human microvascular endothelial cells (HMVECs) can be used to
      engineer new vascular networks. VEGF was incorporated and released in a sustained
      manner from porous poly(lactic-co-glycolic acid) (PLG) matrices to promote
      angiogenesis at the transplantation site. VEGF could be incorporated and released
      in a biologically active form from PLG matrices, with the majority of VEGF
      release (64%) occurring within 2 weeks. These matrices promoted a 260% increase
      in the density of host SCID mouse-derived capillaries invading the matrices after
      7 days of implantation, confirming the activity of the released VEGF. HMVECs were
      transplanted into SCID mice on PLG matrices, and organized to form immature human
      derived vessels within 3 days. Functional vessels were observed within 7 days.
      Importantly, when HMVECs were transplanted on VEGF-releasing matrices, a 160%
      increase in the density of human-derived blood vessels was observed after 14
      days. These findings suggest that combining elements of vasculogenesis and
      angiogenesis provides a viable and novel approach to enhancing local
      vascularization.

PMID- 11948528
TI  - Exploitation of intracellular pH gradients in the cellular delivery of
      macromolecules.
AB  - Most cellular components such as the cytoplasm, endosomes, lysosomes, endoplasmic
      reticulum, Golgi bodies, mitochondria, and nuclei are known to maintain their own
      characteristic pH values. These pH values range from as low as 4.5 in the
      lysosome to about 8.0 in the mitochondria. Given these proton gradients around a
      neutral pH, weak acids, and bases with a pKa between 5.0 and 8.0 can exhibit
      dramatic changes in physicochemical properties. These compounds can be conjugated
      as such to macromolecules or incorporated into polymeric or liposomal
      formulations to promote the efficient cellular delivery of macromolecules.
      Mechanistically, the carrier molecules can facilitate favorable membrane
      partition, membrane fusion, transient pore formation, or membrane disruption.
      Drug carriers equipped with such pH-sensitive triggers and switches are able to
      significantly enhance the cellular delivery of macromolecules in vitro. However,
      the successful application of these molecules for efficient delivery in vivo
      requires the design of noncytotoxic, nonimmunogenic, serum compatible and
      biochemically labile carriers, systematic analysis of their mechanisms of action,
      and extensive animal studies.

PMID- 11948529
TI  - Mannitol-sucrose mixtures--versatile formulations for protein lyophilization.
AB  - Mixtures of sucrose (a lyoprotectant) and mannitol (a bulking agent) have been
      investigated as excipients for the lyophilization of proteins. Four proteins
      under development have been successfully lyophilized in a formulation of 4%
      mannitol and 1% sucrose using a lyophilization cycle that produces a cake of
      crystalline mannitol and amorphous sucrose. The crystalline mannitol allows
      primary drying to be performed with a product temperature of -10 degrees C even
      though the sucrose is amorphous and, by itself, would have required primary
      drying below -35 degrees C to avoid cake collapse. Formation of an unstable
      mannitol hydrate is avoided by conducting secondary drying at 40 degrees C or
      higher.

PMID- 11948530
TI  - Development of a nanofiltration process to improve the stability of a novel anti
      MRSA carbapenem drug candidate.
AB  - The benzenesulfonate salt of an anti-methicillin-resistant Staphylococcus aureus
      carbapenem antibiotic studied is a crystalline, nonhygroscopic powder which is
      stable at room temperature, making it an ideal compound for long-term storage.
      However, the limited aqueous solubility of this salt prohibits parenteral
      administration. Conversely, the chloride salt of this carbapenem demonstrates
      opposing characteristics; it is quantitatively soluble in water, however is
      amorphous and subject to significant hydrolytic degradation in the solid state.
      Given two such extreme alternatives for pharmaceutical salt selection, a common
      approach taken is to develop the bioavailable salt and devise manufacturing and
      storage conditions that minimize degradation. This report describes a different
      approach to this manufacturing dilemma via the application of a simple and
      efficient nanofiltration process to convert the benzenesulfonate salt (storage
      entity) to the chloride salt (formulated drug product). Such an approach combines
      the positive attributes of these two salt forms into a single scalable process
      that reduces processing cycle times via elimination of redundant unit operations,
      increases the flexibility in manufacturing schedule, and improves overall product
      quality.

PMID- 11948531
TI  - A rapid method for pKa determination of drugs using pressure-assisted capillary
      electrophoresis with photodiode array detection in drug discovery.
AB  - We developed a rapid screening method for determination of pK(a) of candidate
      drugs by pressure-assisted capillary electrophoresis (CE) coupled with a
      photodiode array detector. Application of pressure during CE analysis allowed
      completion of one CE run in less than 1 min, and the obtained pH-metric mobility
      shifts as well as pH-metric UV spectrum were analyzed by a nonlinear regression
      fitting software to determine pK(a) values. The difference between pK(a) values
      by this method and by other conventional methods is within 0.25 units for 82
      ionic functional groups of 77 drugs. The pK(a) values of 96 compounds in
      dimethylsulfoxide solution on a 96-well microplate could be measured in 1 day.
      Our method provides rapid and accurate determination of pK(a) value.

PMID- 11948532
TI  - A solid-state NMR study of protein mobility in lyophilized protein-sugar powders.
AB  - The molecular mobility of protein in lyophilized lysozyme-sugar systems stored at
      different relative humidities was studied using solid-state NMR. Relaxation
      measurements, T(1) of high-frequency (MHz), and T(1rho), of low-frequency (kHz)
      motions, were performed on lysozyme lyophilized with lactose and trehalose.
      Molecular aggregation and enzymatic activity of the protein were determined using
      HPLC and bioassays. An increase in hydration had little effect on the T(1rho)
      values of pure lysozyme, trehalose, lactose, trehalose-lysozyme, and lysozyme at
      low lactose concentrations. The T(1) values of pure sugar increased as moisture
      content increased. The presence of both sugars led to increased T(1) values of
      the lysozyme but increasing hydration gradually reduced T(1) values. When a
      larger amount of lactose was lyophilized with lysozyme, longer T(1) (and T(1rho))
      values were seen for lactose than for lysozyme. Although longer T(1) values were
      related to an increase in protein stability, the effect of crystallization and
      sugar type appeared to be major contributing factors. Trehalose and lactose
      decreased relaxation rates in the lysozyme-sugar systems while hydration
      increased relaxation rates that were correlated with changes in aggregation and
      activity of the protein.

PMID- 11948533
TI  - Evaluation of approach to predict the contribution of multiple cytochrome P450s
      in drug metabolism using relative activity factor: effects of the differences in
      expression levels of NADPH-cytochrome P450 reductase and cytochrome b(5) in the
      expression system and the differences in the marker activities.
AB  - The concept of relative activity factor (RAF) to extrapolate data obtained with
      recombinant cytochrome P450(CYP)s to human liver microsomes has been proposed. To
      evaluate the approach to predict the contribution of multiple CYPs using RAF, we
      investigated the effects of the differences in the expression levels of NADPH
      cytochrome P450 reductase (OR) and cytochrome b(5) (b(5)) in recombinant CYPs
      from baculovirus-infected insect cells and the differences in the marker
      activities. Because we previously clarified that azelastine, an antiallergy and
      antiasthmatic drug, is N-demethylated by CYP1A2, CYP2D6, and CYP3A4 in humans,
      the reaction was used as a model. For calculation of RAF, three lots of
      recombinant CYP1A2, CYP2D6, and CYP3A4 from baculovirus-infected insect cells
      with different expression levels of OR and b(5) were used. The OR/CYP ratios for
      recombinant CYP1A2, CYP2D6, and CYP3A4 were 3.9-4.8, 5.1-8.7, and 8.0-11.3,
      respectively. The b(5)/CYP ratio for recombinant CYP3A4 was 2.1-18.7. As marker
      activities, ethoxyresorufin O-deethylation and phenacetin O-deethylation for
      CYP1A2, bufuralol 1'-hydroxylation and debrisoquin 4-hydroxylation for CYP2D6,
      testosterone 6beta-hydroxylation and midazolam 1'-hydroxylation for CYP3A4 were
      compared. Our results indicated that the differences in the expression levels of
      OR and b(5) coexpressed in baculovirus-infected insect cells would not be a
      critical factor for the quantitative prediction using RAF. In addition, we
      confirmed that differences in the marker activities did not significantly affect
      the calculation of RAF values, when the marker activities are specific for a
      certain CYP isoform. It was suggested that the RAF approach using recombinant
      CYPs from baculovirus-infected insect cells coexpressing OR (and b(5) if
      required) could be valuable for the prediction of the contribution of each CYP in
      drug metabolism.

PMID- 11948534
TI  - Modeling of drug release from collagen matrices.
AB  - Drug release from collagen matrices is in most cases governed by diffusion from
      swollen matrices but also enzymatic matrix degradation or hydrophobic
      drug/collagen interactions may contribute. To reduce water uptake and to prolong
      the release, insoluble collagen matrices have been chemically or dehydrothermally
      crosslinked. Assuming Fickian diffusion a one-dimensional model was developed and
      tested that allows description of water penetration, swelling and drug release
      and that may be expanded considering a subsequent erosion process or
      interactions. Swelling is described by a volume balance. For dry collagen
      matrices crosslinked by thermal treatment the existence of a moving front
      separating the polymer from a gel phase was considered, and a convective term
      induced by the volume expansion was incorporated. The resulting moving boundary
      problem was solved using a method based on biquadratic finite elements in both
      space and time that is stable, shows high accuracy, and is suitable for solving
      problems with a singularity at the initial time point. The model was verified for
      insoluble collagen matrices at different crosslinking degrees for both chemical
      and thermal treatment. For constant diffusion coefficients a close form of the
      solution was derived yielding equivalent results to the numerical approach.

PMID- 11948535
TI  - Altered metabolism of orally administered loxoprofen in human subjects after an
      oral administration of loxoprofen for three consecutive days followed by a seven
      day washout.
AB  - The effect of pretreatment (i.e., oral administration of loxoprofen for 3
      consecutive days followed by a 7-day washout) on the pharmacokinetics and
      metabolism of the drug was studied in humans. In a control study, a Loxonin
      tablet (60 mg as loxoprofen anhydrous) was administered orally to 6 healthy male
      Korean subjects. In a pretreatment study, a Loxonin tablet was administered
      orally to the subjects once daily for 3 consecutive days. On the 10(th) day, a
      Loxonin tablet was administered orally to the subjects, and the concentrations of
      loxoprofen and the trans- and cis-alcohol metabolites in the plasma and urine
      were measured as a function of time. Using this pretreatment, the area under the
      curve (AUC) of the trans-alcohol metabolite of loxoprofen in the plasma, but not
      those of loxoprofen and the cis-alcohol metabolite, was increased (1.5-fold, p <
      0.05), leading to increased contribution of the trans-alcohol metabolite to the
      total urinary recovery of loxoprofen (1.3-fold, p < 0.05). The urinary recovery
      of total metabolites, which was largely (> 90%) comprised of conjugate
      metabolites, was also increased as a result of the pretreatment (1.5-fold, p <
      0.05). These results indicate that stereoselective reduction to trans-alcohol
      metabolites as well as the phase II metabolism of loxoprofen may be increased by
      such a pretreatment in human subjects.

PMID- 11948536
TI  - Oral mucosal absorption of midazolam in dogs is strongly pH dependent.
AB  - A significant amount of orally administered midazolam, an anxiolytic and
      sedative, may be absorbed by the mucosal membranes in the oral cavity, esophagus,
      and the stomach. The pH dependence of the opening or closure of a ring in
      midazolam's molecular structure suggests a pH dependence of the mucosal
      absorption, which was evaluated using a dog model. Five milliliters of 5 mg/mL
      midazolam solution, with a pH of 2.8, 3.2, or 3.9, was placed on the buccal
      mucosa of seven anesthetized dogs for 15 min. The same dogs were also infused
      intravenously (iv) with midazolam on separate days. Mean serum Cmax were 92.3 +/-
      42.5 (mean +/- SD), 274.3 +/- 150.8, 377.1 +/- 211.3, and 2552.4 +/- 1305.3 ng/mL
      for pH 2.8, 3.2, 3.9 solutions and iv infusion, respectively. Mean t(max) for all
      buccal solutions and iv infusion was 15 min. Bioavailability for the pH 2.8, 3.2,
      and 3.9 solutions were 6.2, 18.7, and 22.6%, respectively. Because the
      commercially available midazolam syrup and the midazolam-fruit juice blends for
      oral administration have a pH of 2.8 to 3, these results suggest that the
      absorption from the blends or syrup may be significantly improved by slightly
      increasing the pH.

PMID- 11948537
TI  - X-ray powder diffractometric method for quantitation of crystalline drug in
      microparticulate systems. I. Microspheres.
AB  - Ethylcellulose microspheres containing tolnaftate (I) were prepared by the
      emulsion-solvent evaporation technique. An X-ray powder diffractometric method
      was developed to quantify the content of crystalline I in these microspheres. X
      ray lines of I with d-spacings of 5.5 and 4.2 A were chosen for the quantitative
      analyses. Physical mixtures containing various weight fractions of I and blank
      (empty) microspheres were prepared and lithium fluoride (20% w/w) was added as
      the internal standard. The 5.5 and 4.3 A lines of I and the 2.3 A line of lithium
      fluoride were used for the quantitative analysis. A plot of the intensity ratio
      (intensity of the 5.5 A line of I/intensity of 2.3 A line of lithium fluoride) as
      a function of the weight percent of I in the mixture, resulted in a straight
      line. The crystalline content of I in the tolnaftate-loaded microspheres was
      determined using this standard curve. A second independent determination of the
      content of I was possible from the intensities of the 4.3 A line. The enthalpy of
      fusion of I, determined by differential scanning calorimetry (DSC), was also used
      as a measure of the crystalline content of I in the microspheres. The X-ray and
      DSC methods measure the content of crystalline I in the microspheres at room
      temperature ( approximately 25 degrees C) and at the melting point of I (111
      degrees C), respectively. The total content of I in the microspheres was
      determined by HPLC. The DSC and X-ray results indicated that a substantial
      fraction of the incorporated I was dissolved in the ethylcellulose matrix.

PMID- 11948538
TI  - Chromatographic determination of aqueous dissociation constants of some water
      insoluble nonsteroidal antiinflammatory drugs.
AB  - The purpose of this work is to propose a new, useful, and easy chromatographic
      method to determine accurately the aqueous dissociation constant of drugs
      sparingly soluble in water. The method uses the rigorous intersolvental pH scale,
      (w)(s)pH, i.e., the pH measurements are made in the mobile phase after mixing the
      aqueous buffer with methanol by a combined glass electrode previously
      standardised with common aqueous buffers. The measured pK allows the
      determination of the drug's pK(a) in the mobile phase, (w)(s)pK(a), which can be
      easily converted in the aqueous pK(a), (w)(w)pK(a), by means of previously
      established equations. A series of nonsteroidal carboxylic acids with
      antiinflammatory properties were selected to test the method because their
      aqueous pK(a) values, (w)(w)pK(a), had been previously evaluated from different
      approaches that gave consistent results. The comparison of the aqueous pK(a)
      values obtained by means of the proposed procedure with those of literature
      allows the accurate evaluation of this new methodology. The results obtained show
      very good precision and accuracy.

PMID- 11948539
TI  - Salt effects on caffeine solubility, distribution, and self-association.
AB  - In this investigation, salt effects on monomeric solubility and distribution are
      separated from self-association for caffeine. For self-associating compounds, the
      Setschenow equation is inadequate because it does not separate salt effects into
      their different contributions. Solubilities of caffeine, theophylline, and
      theobromine were determined in water and salt solutions at 25 degrees C.
      Caffeine, theophylline, and theobromine solubilities decreased with added
      Na(2)SO(4) or NaCl (i.e., salting-out) and increased with added NaClO(4) or NaSCN
      (i.e., salting-in). Caffeine distribution coefficients (D(W/O)) also decreased
      with added Na(2)SO(4) or NaCl and increased with added NaClO(4) or NaSCN. To
      separate salt-caffeine effects from salt effects on caffeine self-interaction,
      salting parameters (k(s)) were calculated from D(W/O) at infinite dilution
      instead of solubilities with the Setschenow equation. Caffeine k(s) values were
      smaller than the Setschenow constants (K) indicating that, for caffeine, K is not
      simply a salting-in/out parameter. Distribution data were used to characterize
      caffeine self-association using either a dimerization model (k(d), dimerization
      constant) or an isodesmic model (k(iso), stepwise association constant). Caffeine
      self-association constants (k(d) or k(iso)) decreased with NaClO(4) or NaSCN and
      increased with Na(2)SO(4) or NaCl.

PMID- 11948540
TI  - Bioavailability and efficacy of antisense morpholino oligomers targeted to c-myc
      and cytochrome P-450 3A2 following oral administration in rats.
AB  - Antisense phosphorodiamidate Morpholino oligomers (PMO) are resistant to
      degradation by cellular hydrolases, DNases, RNases, and phosphodiesterases, but
      remain sensitive to prolonged exposure to low pH. The present studies evaluate
      the oral fractional bioavailability, stability, and efficacy of two distinct PMO
      sequences targeted to c-myc and cytochrome P-450 (CYP) 3A2. The c-myc antisense
      20-mer, AVI-4126 (5'-ACGTTGAGGGGCATCGTCGC-3'), slowed the regenerative process in
      the rat liver after a 70% partial hepatectomy (PH). Rats were administered 3.0
      mg/kg AVI-4126 in 0.1 mL saline via a bolus intravenous injection or in 0.5 mL
      sterile phosphate-buffered saline via gavage immediately following PH. The areas
      under the plasma concentration versus time curves revealed a fractional oral
      availability of 78.8% over a period of 10 min through 24 h. Immunoblot analysis
      of liver tissue from rats treated orally with AVI-4126 demonstrated a sequence
      specific reduction in the target protein c-Myc, as well as secondary
      proliferation markers: proliferating cell nuclear antigen (PCNA), cyclin D1, and
      p53. The CYP3A2 antisense 22-mer AVI-4472 (5'-GAGCTGAAAGCAGGTCCATCCC-3') caused a
      sequence-dependent reduction of approximately five-fold in the rat liver CYP3A2
      protein levels and erythromycin demethylation activity in 24 h following oral
      administration at a dose of 2 mg/kg. It is concluded that oral administration of
      PMOs can inhibit c-myc and CYP3A2 gene expression in rat liver by an antisense
      based mechanism of action. These studies highlight the potential for development
      of PMOs as orally administered therapeutic agents.

PMID- 11948541
TI  - Pharmaceutical and immunological evaluation of a single-shot hepatitis B vaccine
      formulated with PLGA microspheres.
AB  - A single-shot Hepatitis B vaccine formulation using poly(d,l)-lactide-co
      glycolide acid (PLGA) microspheres as a delivery system was examined using a
      variety of biophysical and biochemical techniques as well as immunological
      evaluation in C3H mice. PLGA microsphere encapsulation of the Hepatitis B surface
      antigen (HBsAg), a lipoprotein particle, resulted in good recoveries of protein
      mass, protein particle conformational integrity, and in vitro antigenicity. Some
      partial delipidation of the HBsAg, however, was observed. The loading and
      encapsulation efficiency of HBsAg into the PLGA microspheres were measured along
      with the morphology and size distribution of the vaccine-loaded PLGA
      microspheres. The in vitro release kinetics of HBsAg from the PLGA microspheres
      was evaluated and found to be affected by experimental conditions such as
      stirring rate. HBsAg showed enhanced storage stability at 37 degrees C in the
      slightly acidic pH range reported to be found inside PLGA microspheres; thus, the
      antigen is relatively stable under conditions of temperature and pH that may
      mimic in vivo conditions. The immunogenicity of the microsphere formulations of
      HBsAg was compared with conventional aluminum adjuvant formulated HBsAg vaccine
      in C3H mice. Comparisons were made between aluminum formulations (one and two
      injections), PLGA microsphere formulations (single injection), and a mixture of
      aluminum and PLGA microsphere formulations (single injection). The nine-month
      serum antibody titers indicate that a single injection of a mixture of aluminum
      and PLGA-formulated HBsAg results in equal or better immune responses than two
      injections of aluminum-formulated HBsAg vaccine. Based on these in vitro and in
      vivo studies, it is concluded that HBsAg can be successfully encapsulated and
      recovered from the PLGA microspheres and a mixture of aluminum-adjuvanted and
      PLGA-formulated HBsAg can auto-boost an immune response in manner comparable to
      multiple injections of an aluminum-formulated vaccine.

PMID- 11948542
TI  - Interrelation between thermochemical and structural data of polymorphs
      exemplified by diflunisal.
AB  - Three known and one new unsolvated polymorphic phase A, B, C, and D of diflunisal
      were grown and studied by X-ray diffraction, IR-spectroscopy, solution
      calorimetry, and DSC methods. Their structures are compared to another previously
      described modification E.1 Relationships were studied between O-H and C=O
      stretching frequencies and between C=O stretching frequency and the molecular
      volume of diflunisal in the respective crystal lattice. According to regularities
      found it was proposed that the existence of polymorphic forms is determined by
      conformational flexibility of the molecule, ability to create inter- and
      intramolecular hydrogen bonds and the competition between nonspecific van der
      Waals and specific hydrogen bond interactions. The volume per molecule in the
      crystal lattice are: A < B < C < E < D (XRD Ito method). Forms A and C are
      enantiotropic with a difference in crystal lattice energies of 1.9 +/- 0.5
      kJ.mol( - 1). Modifications B, C, D, and A, B, D are monotropic. Based on
      solution enthalpies, absolute values of the lattice showed only small differences
      ("isoenergetic" polymorphs), and can be arranged in increasing order: B
      approximately A < C < D.

PMID- 11948543
TI  - A statistical method for the determination of absorption rate constant estimated
      using the rat single pass intestinal perfusion model and multiple linear
      regression.
AB  - The guide "Waiver of In Vivo Bioavailability and Bioequivalence Studies for
      Immediate Release Solid Dosage Forms Containing Certain Active Moieties/Active
      Ingredients Based on a Biopharmaceutical Classification System" (Rockville, MD:
      CDER, 2000) outlined non-in vivo tests of permeability that may satisfy the
      classification of a compound in the biopharmaceutical classification system.
      However, absent from that document were specific statistical methods to
      legitimatize the non-in vivo tests. This report describes the appropriate
      statistical treatment of absorption data, and recommends its adoption in the
      estimation of absorption and/or permeability measurements. The calculation of the
      absorption rate constants (k(a)) of ten compounds by a new multiple linear
      regression (MLR) method was completed after the separate perfusion of each
      compound through the rat single pass intestinal perfusion model (n = 3 rats per
      compound). Studentized residuals were evaluated to determine whether any
      statistically significant outliers were present in the data. The standard error
      of k(a) was estimated using variance components from the random effects model.
      The results were compared with the "traditional method" for k(a) calculations.
      Although both methods produced similar values of k(a), the MLR method's error
      estimate included multiple components of variability, which was largely ignored
      by the traditional method. The MLR method provided objective tests for outliers
      and achievement of steady-state. A preferred method for the statistical analysis
      of absorption data was demonstrated. These methods should be applied to all forms
      of permeability measurements, especially the non-in vivo measurements that
      classify a compound in the biopharmaceutical classification system.

PMID- 11948544
TI  - Exposure to a deuterated analogue of phenylbutyrate retards S-phase progression
      in HT-29 colon cancer cells.
AB  - Differentiation agents that induce neoplastic cells to regain a normal phenotype
      and/or cause growth arrest without significantly affecting normal cells represent
      an attractive option for cancer treatment. Analogues of short chain fatty acids,
      such as phenylbutyrate (PB), have been studied as clinically relevant agents. In
      an attempt to improve its pharmacokinetic profile, structural modifications of PB
      and other fatty acids have been studied. We hypothesize that strategic isotopic
      modification of PB would result in a longer half-life and thus translate into a
      more potent differentiation agent for clinical use. Using a colon cancer model,
      we demonstrated that 2,2,3,3-tetradeuterated PB (D4PB) significantly increased
      induction of apoptosis and inhibition of cell proliferation as compared with PB
      and butyrate. Difference in potency could not be explained by the effect of D4PB
      on the expression of specific regulatory proteins of the apoptotic cascade or
      from the inhibitory effect of D4PB on histone deacetylase activity.
      Interestingly, exposure of HT-29 colon cancer cells to D4PB resulted in a slowing
      of S transit, in contrast to butyrate and PB, which induced a G2/M cell cycle
      block. This difference in cell cycle effect may explain the differences seen in
      the potency of the phenotypic changes seen with treatment with D4PB. Further
      studies are needed to elucidate the mechanisms underlying effects of D4PB on the
      cell cycle.

PMID- 11948546
TI  - A rapid empirical method for measuring membrane bilayer entry equilibration of
      molecules.
AB  - The therapeutic potency of many drugs is limited by their interactions with cell
      membranes. The ability of a drug to cross lipid barriers, such as those of cell
      membranes and the blood-brain barrier, to reach its site of action can be the
      determining factor in the effectiveness of a drug. In this paper we demonstrate
      the utility of fluorescently labeled liposomes, Fluorosomes, to measure the rate
      of penetration of small molecules into membrane lipid bilayers. This technique
      can be used to determine the half-times of bilayer entry equilibration of drugs
      of from milliseconds to hours for a wide variety of compound types at micromolar
      drug concentrations. This in vitro technique for measuring the nonprotein
      facilitated entry of drugs into the lipid phase of the membrane is suitable for
      the high-throughput screening of drugs.

PMID- 11948547
TI  - A study of the molecular properties of water in hydrated mannitol.
AB  - An understanding of the properties of water in hydrated saccharides and
      saccharide derivatives is relevant to a number of pharmaceutical processes,
      including wet granulation. This study uses a range of physical measurement
      techniques [viz. nuclear magnetic resonance spectroscopy (NMR), dielectric
      relaxation spectroscopy (DRS), near infrared spectroscopy (NIR), and differential
      scanning calorimetry (DSC)] to analyze the molecular properties of water in
      hydrated mannitol (containing up to 0.45 g water per gram of dry sample). The
      resulting measurements show a correlation between the different techniques, in
      that each technique shows two transitions (h(t1) and h(t2)) in the properties of
      the hydrated material (at water contents of approximately 0.1 g/g and 0.25-0.3
      g/g, respectively). It is suggested that h(t1) and h(t2) mark the appearance of a
      second and a third population of water and that these transitions are due to
      different stages of microdissolution of the solid. Evidence is presented that
      shows that this second population of water undergoes a thermodynamic phase
      transition close to 0 degrees C, and therefore the material must contain some
      water that is behaving like free water. The significance of the transitions
      (h(t1) and h(t2)) and the mobility of water (above and below these transitions)
      are yet to be established for mixtures of sugars and other materials. However, it
      is probable that this information will contribute to our understanding of the how
      these types of materials are processed (e.g., during the wet granulation process)
      and how drugs maintain their stability during processes that involve the
      significant hydration of a powder blend.

PMID- 11948545
TI  - Semisolid, self-catalyzed poly(ortho ester)s as controlled-release systems:
      protein release and protein stability issues.
AB  - Semisolid, self-catalyzed poly(ortho ester)s (POEs), are investigated as
      potential sustained-release systems for proteins. In this study, some factors
      influencing protein release kinetics and protein instability were evaluated. As
      model proteins, lysozyme, alpha-lactalbumin, bovine serum albumin, and vascular
      endothelial growth factor, which were lyophilized from various buffer solutions
      in the absence and presence of lyoprotectants, were used. For all protein
      formulations, the release kinetics followed the visually observed polymer
      dissolution profile. In the absence of any buffers in the protein formulation,
      the release was continuous. Formulations containing a buffer below pH 7
      accelerated POE degradation, resulting in faster protein release. In contrast, a
      strong buffer capacity at pH 7 reduced the POE degradation and resulted in a
      biphasic release pattern. Moreover, proteins with a high isoelectric point (pI >
      7) appeared to catalyze the POE degradation, and the effect of the buffer
      strength and pH was much smaller than for proteins with low pI (< 7). In the
      absence of lyoprotectants, all proteins tested showed an increasing fraction of
      covalent protein aggregates during the release. Protein formulations containing a
      lyoprotectant, such as sucrose or trehalose, did not show a significantly
      increased aggregation, whereas there was a minor influence of the large solid
      loadings on the release kinetics. In conclusion, this semisolid, self-catalyzed
      POE showed good promise as a sustained-release matrix for bioactive proteins.

PMID- 11948548
TI  - Crystallization and transitions of sulfamerazine polymorphs.
AB  - A bulk powder of sulfamerazine polymorph II in a narrow distribution of particle
      size was prepared for the first time. The two known sulfamerazine polymorphs, I
      and II, were physically characterized by optical microscopy, powder X-ray
      diffractometry, differential scanning calorimetry, carbon-13 solid-state nuclear
      magnetic resonance spectroscopy, and measurements of aqueous solubility and
      density. The thermodynamics and kinetics of the transition between the polymorphs
      was examined under various pharmaceutically relevant conditions, such as heating,
      cooling, milling, compaction, and contact with solvents. The two polymorphs were
      found to be enantiotropes with slow kinetics of interconversion. The
      thermodynamic transition temperature lies between 51 and 54 degrees C, with
      polymorph II stable at lower temperatures. Ostwald's Rule of Stages explains the
      crystallization of the polymorphs from various solvents and may account for the
      delay in the discovery of polymorph II.

PMID- 11948549
TI  - Solvation mechanisms of nedocromil sodium from activation energy and reaction
      enthalpy measurements of dehydration and dealcoholation.
AB  - Two independent athermal methods of analysis have been used to determine the
      activation energies associated with the dehydration of nedocromil sodium
      hydrates. For the highest temperature reaction, monohydrate to the anhydrate, the
      differences in the measured activation energies indicate a three-dimensional
      nucleation mechanism in the bulk of the crystal with subsequent three-dimensional
      anhydrate crystal growth. The number of critical nuclei varies inversely with
      heating rate. Measured enthalpy values for successive removal of water molecules
      at 31.7 +/- 1.0, 91.3 +/- 0.8, and 193 +/- 0.6 degrees C are the same, within
      experimental error, at 21.6 +/- 2.6 kJ (mol H(2)O)(-1), as determined from
      differential thermal analysis traces. This result implies that an earlier concept
      of "strong" and "weak" water binding is not relevant and temperatures at which
      H(2)O molecules are removed is related to nucleation effects and not bond
      energies. The low temperature shoulder on the 91.3 degrees C peak is identified
      as an effect arising from open pan analysis conditions. The appearance of
      "transient" peaks in the conditioning stage of nedocromil sodium trihydrate
      thermal analysis experiments have been investigated and an explanation based on
      the presence of alcoholates [(NS)(4) small middle dot 5CH(3)OH, (NS)(5) small
      middle dot 9C(2)H(5)OH, and (NS)(2) small middle dot C(3)H(7)OH] in the
      preparations is proposed.

PMID- 11948550
TI  - The use of xanthan gum in an ophthalmic liquid dosage form: rheological
      characterization of the interaction with mucin.
AB  - The development of an ocular dosage form containing xanthan gum and capable of
      interacting with mucin in the precorneal area is a challenge. The polymer
      concentration that can be applied is restricted because of the limited patient
      acceptability of highly viscous preparations. The precorneal mucin concentration
      is low and the high ionic strength of the lachrymal fluid forces xanthan gum in
      an ordered structure, less capable of interacting through heterotypic junctions.
      Intrinsic viscosity measurements and shear rheometry are used to investigate the
      effect of several factors (polymer concentration, additional boiling or
      sonication step to the preparation procedure) on the physicochemical properties
      of xanthan gum and the degree of interaction with a low (8%, w/v) and high
      (16.0%, w/v) concentrated mucin dispersion. Independent of the preparation
      procedure applied, a xanthan gum concentration of 1.0% (w/v) is required to
      obtain a measurable interaction with mucin. If an extra boiling or sonication
      step is added to the standard preparation procedure, the minimum mucin
      concentration necessary to achieve formation of heterotypic junctions is
      decreased. Only by sonication of the highly concentrated xanthan gum dispersion
      is the viscosity decreased to a level that is tolerable and comfortable to the
      patient. The findings of the present study clearly demonstrate that a significant
      interaction between a tolerable and comfortable ocular dosage form containing
      xanthan gum, and mucin 8% (w/v), is feasible after sonication of a highly
      concentrated polymer dispersion.

PMID- 11948551
TI  - Antitumor effects and pharmacokinetics of aclacinomycin A carried by injectable
      emulsions composed of vitamin E, cholesterol, and PEG-lipid.
AB  - The aim of this study was to prepare injectable emulsions of aclacinomycin A (E
      ACM) and evaluate its acute toxicity, antitumor effects, and pharmacokinetics. In
      E-ACM, the surfactants were polyethylene glycol-lipid and cholesterol, and the
      oil phase was a vitamin E solution of ACM. The particle size distribution and the
      zeta potential of E-ACM were measured by the laser light dynamic scattering
      method. The ACM-loading efficiency was measured by using Sephadex G50 column
      chromatography. The acute toxicity, antitumor effects, and pharmacokinetics of E
      ACM were studied in C57BL/6 mice bearing mouse murine histiocytoma M5076 tumors.
      The average diameter, zeta potential, and ACM-loading efficiency of E-ACM were
      123.0 +/- 1.2 nm, - 12.67 +/- 1.35 mv, and 96.3 +/- 0.3% (n = 3), respectively.
      When stored at 7 degrees C in the dark for 1 year, the average diameter and ACM
      loading efficiency of E-ACM changed into 126.3 +/- 2.3 nm and 97.4 +/- 0.8%,
      respectively, whereas 6.5 +/- 0.2% ACM decomposition was observed (n = 3). The
      plasma areas under the biodistribution curves (AUC)(0.03-48h) of E-ACM was
      significantly greater than that of free ACM (F-ACM). The heart, lung, and kidney
      AUC(0.03-48h) of E-ACM were significantly smaller than those of F-ACM whereas the
      liver and spleen AUC(0.03-48h) of E-ACM were not significantly different from
      those of F-ACM. The tumor AUC(0.03-48h) of E-ACM was significantly greater than
      that of F-ACM. E-ACM had lower acute toxicity and greater potential antitumor
      effects than F-ACM in M5076 tumor-bearing C57BL/6 mice. E-ACM is a useful tumor
      targeting drug delivery system.

PMID- 11948552
TI  - Insulin aggregation and asymmetric transport across human bronchial epithelial
      cell monolayers (Calu-3).
AB  - The purpose of this work was to elucidate the transport pathways of zinc insulin
      across the Calu-3 cell monolayer, an in vitro model of the human airway
      epithelium. Calu-3 cells grown in liquid-covered conditions formed a confluent
      monolayer with a high transepithelial electrical resistance value of 1000 +/- 150
      Omega small middle dot cm(2). The cell monolayer was characterized by a low
      mannitol permeability of 4.7 +/- 0.5 10(-7)cm/s. Transport of zinc insulin (donor
      concentration 1 U/mL) in Dulbecco's modified phosphate buffer saline at 37
      degrees C was found to be higher in the basolateral (BL) to apical (AP) (P(app) =
      3.0 +/- 0.2 10(-8) cm/s), than in the AP to BL direction (P(app) = 0.41 +/- 0.02
      10(-8) cm/s). P-glycoprotein efflux or specific enzymatic degradation did not
      appear to contribute toward this asymmetric transport. Insulin receptors, though
      apparently more abundant on the BL side than on the AP side of Calu-3 cells, did
      not mediate the direction-dependent transport of insulin. However, transport of a
      monomeric human insulin analog, Asp(B10)des(B28-30), across the Calu-3 cell
      monolayer was similar in both directions (BL to AP and AP to BL). The
      corresponding permeability, P(app) = 2.9 +/- 0.2 10(-8) cm/s, was not
      significantly different from the permeability of zinc insulin in the BL to AP
      direction. The paracellular pathway seems to play a major role in the insulin
      transport across the Calu-3 cell monolayers. We hypothesize that the transport of
      zinc insulin oligomers is restricted at the AP surface by the presence of the
      tight junctional complexes. From the BL side, oligomers may undergo dissociation
      in the intercellular space and diffuse readily as monomers to the AP surface of
      the membrane.

PMID- 11948553
TI  - Freeze-drying of tert-butanol/water cosolvent systems: a case report on formation
      of a friable freeze-dried powder of tobramycin sulfate.
AB  - A case study is presented in which a tert-butanol (TBA)/water cosolvent system
      was found to be a useful means of producing freeze-dried tobramycin sulfate that
      readily forms a loose powder upon agitation in a specialized application in which
      a critical quality attribute is the ability to pour the sterile powder from the
      vial. Both formulation and processing variables are important in achieving
      acceptable physical properties of the cake as well as minimizing residual TBA
      levels. Liquid/liquid phase separation was observed above critical concentrations
      of both drug and TBA, resulting in a two-layered lyophilized cake with
      unacceptable appearance, physical properties, and residual TBA levels. However,
      the choice of tobramycin sulfate and TBA concentrations in the single-phase
      region of the phase diagram resulted in a lyophilized solid that can readily be
      poured from vials. Crystallization of TBA before drying is critical to achieving
      adequately low residual TBA levels, and this is reflected in the effect of
      thermal history of freezing on residual TBA levels, where rapid freezing results
      in incomplete crystallization of TBA and relatively high levels of residual
      solvent. Annealing at a temperature above T'(g) of the system after an initial
      freezing step significantly reduces the level of residual TBA. Secondary drying,
      even at increased temperature and for extended times, is not an effective method
      of reducing residual TBA levels.

PMID- 11948554
TI  - An evaporation study for phthalic acids--a rapid method for pharmaceutical
      characterization.
AB  - The objective of this study was to develop and analyze an analytical method in
      order to evaluate preformulation candidates by their thermodynamic parameters and
      evaporation characteristics. Ortho, meta and tere-phthalic acids were chosen as
      model compounds. The relative advantages and disadvantages of a rapid
      thermogravimetric method have been studied in detail, which would aid in the
      preformulation characterization for pharmaceuticals. Methyl paraben was taken as
      the model compound for calibration, as its evaporation characteristics are well
      known. Using the Antoine and the Langmuir equation for evaporation conjointly,
      the parameter k, known as the coefficient of evaporation was determined. The
      value for this constant was validated by three methods simultaneously. Previously
      the use of such methods for compounds having uninhibited zero order evaporation
      has been documented. In the present study, phthalic acid was chosen as the model
      compound since its evaporation is a two-step overlapping phenomenon. In this
      study we have shown the use of Pressure Differential Scanning Calorimetry in
      separating such simultaneous endothermic processes. The Clausius-Clapeyron
      equation seemingly has anomalous behavior for vapor pressure over high
      temperature ranges. In this study a modification of the equation has been
      suggested to take into account the changes in the heat capacities that result due
      to high temperature effects. This study aims at documenting a concise method for
      rapid pharmaceutical characterization and suggests modifications for some basic
      thermodynamic parameters over higher temperature ranges.

PMID- 11948555
TI  - Contributions of saturable active secretion, passive transcellular, and
      paracellular diffusion to the overall transport of furosemide across
      adenocarcinoma (Caco-2) cells.
AB  - Furosemide permeation across Caco-2 cells was investigated to determine if
      previously reported directional differences in transport rates are due to a
      saturable, energy dependent process. In addition, studies were carried out to
      determine the route of permeation for this drug. By comparing apical (A) to
      basolateral (B) and B to A directional transport across Caco-2 cells, a
      saturable, nonlinear component to furosemide transport was observed. Transport in
      the secretory direction was fit to yield the following apparent parameters K(m) =
      63 +/- 28 microM, V(max) = 436 +/- 137 pmol/cm(2)h, and P(app) = 3.7 +/- 0.9 x
      10(-7) cm/s. Evidence of energy dependence was demonstrated using both metabolic
      inhibition, and transport against a diffusion gradient methods. Disruption of
      tight junctions by use of the calcium chelator, EGTA, caused a significant
      increase in furosemide transport (twofold and 12-fold increases in B to A and A
      to B, respectively) indicating the importance of the paracellular route. We
      conclude that furosemide secretion from Caco-2 cells is the result of saturable
      active transport and passive diffusion that has a significant paracellular
      component.

PMID- 11948556
TI  - Amphotericin B in oil-water lecithin-based microemulsions: formulation and
      toxicity evaluation.
AB  - A novel lecithin-based microemulsion containing AmB was developed to reduce the
      toxic effects of the drug, comparing it with the commercial formulation
      Fungizone. Phase diagrams containing the microemulsion region were constructed
      for pseudoternary systems composed of isopropil myristate (IPM)/Brij((R))
      96V/lecithin/water. The incorporation of AmB to the microemulsions was done
      following the Phase Inversion Temperature (PIT) method or by diluting the drug in
      the aqueous phase of the disperse system before forming the microemulsion. The
      percentage of drug entrapped in the microemulsion was analyzed by an HPLC method
      obtaining recoveries > 98%. Mean droplet size of the microemulsions chosen for
      the acute toxicity evaluation was of 45 nm, and the rheological studies showed
      that those microemulsions mentioned followed a Newtonian behavior. Different
      studies are described in this work to prove the stability of these new dosage
      forms. Acute toxicity results, determined by a graphic method, the probit binary
      model and the Reed and Muench method showed that lethal dose 50 (LD(50)) for AmB
      microemulsions was of 2.9 mgkg(-1) compared to 1.4 mgkg(-1) for the commercial
      deoxycholate suspension, Fungizone. The overall results indicate that treatment
      with AmB microemulsions was less toxic than Fungizone, suggesting a potential
      therapeutic application.

PMID- 11948557
TI  - Form IV of carbamazepine.
AB  - Carbamazepine has been found to crystallize as a new polymorph that is stable at
      room temperature. We report the crystal structure of this C-centered monoclinic
      form (space group C2/c, cell parameters: a = 26.609, b = 6.9269, c = 13.957, beta
      = 109.702), which consists of hydrogen bonded dimers with an anti-disposition.
      This represents the third modification of carbamazepine that has been
      crystallographically characterized, and the fourth for which cell parameters have
      been determined. Thus, it is designated as form IV of carbamazepine. Differences
      between the packing of the various polymorphs are discussed.

PMID- 11948558
TI  - Preparation and properties of alginate lyase modified with poly(ethylene glycol).
AB  - Modification of the enzyme alginate lyase (AL) with poly(ethylene glycol) (PEG)
      was attempted for the degradation and removal of alginate biofilms in infectious
      diseases. The modification of AL with PEG was attempted with three kinds of N
      succinimidyl succinate PEG (SS-PEG), which differed in molecular weight (i.e.,
      2000, 5000 and 12,000 Da). The conjugation of PEG to free amino groups on AL was
      confirmed by gel permeation chromatography. Quantification of residual free amino
      groups revealed that PEG modification progressed further with a higher pH and a
      larger molar ratio of SS-PEG to AL. The reproducibility of the reaction was
      fairly good. The enzyme activity decreased with increasing PEG modification but
      the immunoreactivity toward anti-AL antibodies, as evaluated by an ELISA method,
      was much more remarkably reduced. The immunoreactivity was more reduced by the
      conjugated PEG with the larger molecular weight. In the reaction with PEG of
      molecular weight 12,000 Da, we obtained PEG-modified AL retaining approximately
      40% enzyme activity but only 0.5% of the immunoreactivity of native AL.

PMID- 11948559
TI  - Solvents and color vision.

PMID- 11948562
TI  - The two sites of fusion of the neural folds and the two neuropores in the human
      embryo.
AB  - BACKGROUND: Since reports on a pattern of multiple sites of fusion of the neural
      folds in the mouse appeared, it has been widely assumed that a similar pattern
      must be valid for the human. In the absence of embryological evidence, claims
      have been made that such a pattern can be discerned by classifying neural tube
      defects. METHODS: The neural folds and tube, as well as the neuropores, were
      reassessed in 98 human embryos of Stages 8-13; 61 were controlled by precise
      graphic reconstructions. RESULTS: Careful study of an extensive series of staged
      human embryos shows that two de novo sites of fusion of the neural folds appear
      in succession: alpha in the rhombencephalic region and beta in the prosencephalic
      region, adjacent to the chiasmatic plate. Fusion from Site alpha proceeds
      bidirectionally (rostrad and caudad), whereas that from beta is unidirectional
      (caudad only). The fusions terminate in neuropores, of which there are two:
      rostral and caudal. Highly variable accessory loci of fusion, without positional
      stability and of unknown frequency, may be encountered in Stage 10 but seemingly
      not later, and their existence has been known for more than half a century.
      CONCLUSIONS: Two sites of fusion (a term preferred to closure) of the neural
      folds and two neuropores are found in the human embryo. No convincing
      embryological evidence of a pattern of multiple sites of fusion, such as has been
      described in the mouse, is available for the human. The construction of
      embryological details from information derived from other species or from the
      examination of later anomalies is liable to error. Neural tube defects are
      reviewed and although they have been considered on the basis of five, four, or
      three sites of fusion, interpretations based on two sites can as readily be
      envisaged.

PMID- 11948561
TI  - Update on new developments in the study of human teratogens.
AB  - BACKGROUND AND METHODS: The purpose of this annual article is to highlight and
      briefly review new and significant information on agents that may be teratogenic
      in pregnant women. Various sources of on-line and printed information are given.
      RESULTS: The following topics have been discussed: 1) lithium medication:
      decreased estimate of risk; 2) cigarette smoking and genotype as contributors to
      oral-facial clefts and clubfoot; 3) trimethoprim; 4) methimazole syndrome?; 5)
      glucocorticoids and oral-facial clefts; 6) binge drinking; 7) fetal valproate
      syndrome; and 8) carbamazepine. CONCLUSIONS: We have highlighted several maternal
      exposures during pregnancy that are associated with small but increased rates of
      birth defects, generally only a few cases per 1,000 infants. These exposures
      include cigarette smoking, and treatment with lithium, trimethoprim, methimazole,
      or corticosteroids. This weak teratogenic effect was usually identified by the
      linkage of an uncommon treatment with an unusual birth defect outcome. The use of
      modern epidemiologic techniques, especially prospective multicenter studies that
      provide increased numbers, has helped to strengthen the evidence for these
      associations. We discuss how teratogenic risks that are small in comparison to
      the background risk can be presented to at-risk women and their doctors. We have
      briefly listed some elements that might be used in prioritizing further studies
      of suspected teratogenic exposures. Various existing methods for expressing the
      strength of evidence for human teratogenicity are also given.

PMID- 11948563
TI  - Homocysteine modifies development of neurulation and dorsal root ganglia in chick
      embryos.
AB  - BACKGROUND: The formation of the neural tube (neurulation) involves two
      mechanisms: primary and secondary neurulation. In chicks, there is also an
      overlap zone, where both mechanisms work together. Homocysteine (Hcy) may have an
      important teratogenic role in neural tube defects (NTD) when folic acid levels
      are considered normal. Recently, Hcy capability to generate NTD and modify neural
      crest cell migration has been demonstrated in chick embryos. This study was aimed
      to evaluate the effects of Hcy on neurulation and the development of the dorsal
      root ganglia (DRG). METHODS: Chick embryos were treated with L-Hcy thiolactone 20
      micromol to produce the highest rate of survival with embryos carrying neural
      tube defect (NTD) in the spine. Embryos at stages (st) 3-10 were treated and
      harvested at st 18-23. Only externally normal embryos or those carrying spinal
      NTD embryos were considered. RESULTS: Histological sections of Hcy-treated
      embryos showed: open spina bifida (39% of embryos), more than one tube forming
      the spinal cord (26%), disorganized spinal cord (26%), always affecting
      lumbosacral regions, probably in the overlap zone. Additionally, 32% of embryos
      had small and continuous DRG, associated with a slimmed roof plate. Three
      dimensional reconstruction showed unsegmented DRG until the C8 ganglion level.
      There was a 75% reduction of C3 DRG cells in treated embryos in comparison to
      untreated ganglia. CONCLUSION: Hcy teratogenicity in avian embryos affected the
      neural tube in the overlap zone, secondary neurulation and the cervical DRG.

PMID- 11948564
TI  - 5-Aza-2'-deoxycytidine-induced cytotoxicity and limb reduction defects in the
      mouse.
AB  - BACKGROUND: 5-Aza-2'-deoxycytidine (dAZA), causes hindlimb phocomelia in CD-1
      mice. Studies in our laboratory have examined the hypothesis that compound-
      induced changes in gene expression may uniquely affect hindlimb pattern
      formation. The present study tests the hypothesis that dAZA causes limb dysplasia
      by inducing cytotoxicity among rapidly proliferating cells in the limb bud
      mesenchyme. METHODS: Pregnant CD-1 mice were given a teratogenic dose of dAZA
      (i.p.) at different times on GD 10 and fetuses evaluated for skeletal development
      in both sets of limbs by standard methods. Using general histology and BrdU
      immunohistochemistry, limb mesenchymal cell death and cell proliferation were
      then assessed in embryos at various times post dosing, shortly after initial limb
      bud outgrowth. The effect of dAZA on early limb chondrogenesis was also studied
      using Northern analysis of scleraxis and Alcian blue staining of whole mount limb
      buds. RESULTS: Compound related hindlimb defects were not restricted to a
      specific set of skeletal elements but consisted of a range of temporally related
      limb anomalies. Modest defects of the radius were observed as well. These results
      are consistent with a general insult to the limb mesenchyme. Mesenchymal cell
      death and reduced cell proliferation were also observed in both sets of limbs.
      The timing and location of these effects indicate a role for cytotoxicity in the
      etiology of dAZA induced limb defects. These effects also agree with the greater
      teratogenicity of dAZA in the hindlimb because they were more pronounced in that
      limb. The expression of scleraxis, a marker of early chondrogenesis, was reduced
      12 hr after dAZA exposure, a time coincident with maximal cell death, as was the
      subsequent emergence of Alcian blue stained long bone anlagen. CONCLUSIONS: These
      findings support the hypothesis that cytotoxic changes in the limb bud mesenchyme
      during early limb outgrowth can induce the proximal limb truncations
      characteristic of phocomelia after dAZA administration.

PMID- 11948565
TI  - Ethical framework for observational studies of medicinal drug exposure in
      pregnancy.
AB  - BACKGROUND: The conduct of human research in the teratogenicity of drugs,
      chemicals, radiation and infections is needed in order to close critical gaps in
      knowledge. METHODS: We reviewed the various aspects of the ethics of conducting
      prospective human research in teratogenicity. RESULTS: Such research should
      respect the confidentiality of pregnant women and their families. Because this
      research is observational, interpretation of results is difficult, and the study
      design should strive to meet the highest possible scientific standards attainable
      in the particular research conditions. It should also be acknowledged that
      confidentiality cannot be always adhered to (e.g., if the interview reveals risks
      to minors). CONCLUSIONS: In general, the benefit risk ratio in this type of
      research is very favorable, although in specific cases the research follow-up may
      induce fears (e.g., drugs of abuse) in the woman being interviewed.

PMID- 11948566
TI  - Sonographic measurement of the volume of the left lateral segment of the liver.
AB  - PURPOSE: The aim of this study was to evaluate the accuracy of sonography for
      measuring the volume of the left lateral segment of the liver. METHODS: The
      volume of the left lateral segment of the liver was measured with sonography in
      101 consecutive patients who were hospitalized between December 1998 and January
      2000 for hepatic, biliary, or pancreatic disease or who were donors for a living
      related liver transplantation. The results were compared with those obtained
      using CT. RESULTS: The mean calculated volume of the left lateral segment of the
      liver +/- standard deviation was 261 +/- 118 cm(3) by sonography compared with
      274 +/- 123 cm(3) by CT. The relationship between the results of both imaging
      modalities was linear and statistically significant (r = 0.93; p < 0.0001).
      CONCLUSIONS: Our study demonstrated that sonography has an acceptable level of
      accuracy and reliability for routine measurement of the volume of the left
      lateral segment of the liver.

PMID- 11948567
TI  - Role of systematic ultrasound-guided staging biopsies in predicting
      extraprostatic extension and seminal vesicle invasion in men with prostate
      cancer.
AB  - PURPOSE: To assess the presence of extraprostatic extension and seminal vesicle
      invasion in men with prostate cancer, we performed systematic staging biopsies
      targeting neurovascular bundles, seminal vesicles, and other extraprostatic
      tissues before the men underwent radical prostatectomy. We retrospectively
      evaluated the clinical efficacy of these systematic staging biopsies compared
      with digital rectal examination (DRE) and transrectal sonography (TRUS). METHODS:
      Two hundred forty-four candidates for prostatectomy who had a diagnostic biopsy
      Gleason score of 8 or higher and/or indications of extraprostatic extension (eg,
      seminal vesicle invasion) by DRE or TRUS underwent staging biopsies using an 18
      gauge Tru-Cut needle under real-time TRUS guidance between June 1997 and March
      2000. We determined the number of staging biopsy cores to be taken based on the
      Gleason score of the diagnostic biopsy as well as abnormal DRE and/or TRUS
      findings. The chi-square test was used to evaluate the statistical significance
      of differences. RESULTS: There were no complications of staging biopsy. In 75
      (31%) of the 244 patients, results of the staging biopsies were positive. The
      clinical stage was upgraded by staging biopsy in 18 (24%) of these 75 patients.
      After the staging biopsies, 90 patients underwent radical prostatectomy. Among
      these 90 patients, staging biopsy specimens were positive for cancer in 20 (47%)
      of the 43 patients who received neoadjuvant therapy and in 1 (2%) of the 47
      patients who did not receive neoadjuvant therapy. There were no false-positive
      staging biopsies in either group. Among the 90 patients who underwent radical
      prostatectomy, the false-negative rate for the prediction of organ-confined
      disease was 43% (30/69) for staging biopsies compared with 29% (10/34) for TRUS.
      The diagnostic accuracy of staging biopsies (67%; 60/90) was higher than that of
      DRE (52%; 47/90; p < 0.05) but lower than that of TRUS (79%; 71/90; p = 0.066).
      CONCLUSIONS: Staging biopsies can reliably sample extraprostatic tissue,
      including the seminal vesicles and neurovascular bundles. Positive staging biopsy
      results can aid in the selection of treatment options and in the prediction of
      outcome for individual patients by providing definitive histologic confirmation
      of locally advanced disease. Conventional predictive variables for staging can be
      applied when the results of staging biopsies are negative.

PMID- 11948568
TI  - Changes in blood flow velocity in the middle and anterior cerebral arteries
      evoked by walking.
AB  - PURPOSE: Transcranial Doppler sonography (TCD) is an established method for
      assessing changes in blood flow velocity (BFV) coupled to brain activity. Our
      objective was to investigate whether walking induces measurable changes in BFV in
      healthy subjects. METHODS: Changes in BFV in both middle cerebral arteries (MCAs)
      of 40 healthy adult subjects during walking on a treadmill were measured using
      bilateral TCD. In 8 of the 40 subjects, 1 anterior cerebral artery (ACA) was
      monitored simultaneously with the contralateral MCA. The percentage increase in
      BFV (BFVI%) compared with the baseline velocity (V(0)), the percentage decrease
      in BFV (BFVD%) compared with the V(0), and the normalized ACA-MCA ratio were
      analyzed. RESULTS: The overall mean (+/- standard deviation [SD]) V(0) was 59.9
      +/- 11.6 cm/second in the left MCA and 60.1 +/- 12.9 cm/second in the right MCA.
      Women had higher V(0) values than men had. Walking evoked an initial mean overall
      BFVI% in both left (8.4 +/- 5.1%) and right MCAs (9.1 +/- 5.1%), followed by a
      decrease to below baseline values in 38 of 40 subjects. A statistically
      significant increase of the normalized ACA-MCA ratio was measured, indicating
      that changes in BFV in the ACA territory were coupled to brain activation during
      walking. CONCLUSIONS: The use of functional TCD showed different changes in BFV
      in the ACAs and MCAs during walking. This method may be an interesting tool for
      monitoring progress in patients with motor deficits of the legs, such as paresis.

PMID- 11948569
TI  - Menstrual age-dependent systematic error in sonographic fetal weight estimation:
      a mathematical model.
AB  - PURPOSE: We used computer modeling techniques to evaluate the accuracy of
      different types of sonographic formulas for estimating fetal weight across the
      full range of clinically important menstrual ages. METHODS: Input data for the
      computer modeling techniques were derived from published British standards for
      normal distributions of sonographic biometric growth parameters and their
      correlation coefficients; these standards had been derived from fetal populations
      whose ages were determined using sonography. The accuracy of each of 10 formulas
      for estimating fetal weight was calculated by comparing the weight estimates
      obtained with these formulas in simulated populations with the weight estimates
      expected from birth weight data, from 24 weeks' menstrual age to term. Preterm
      weights were estimated by interpolation from term birth weights using sonographic
      growth curves. With an ideal formula, the median weight estimates at term should
      not differ from the population birth weight median. RESULTS: The simulated output
      sonographic values closely matched those of the original population. The accuracy
      of the fetal weight estimation differed by menstrual age and between various
      formulas. Most methods tended to overestimate fetal weight at term. Shepard's
      formula progressively overestimated weights from about 2% at 32 weeks to more
      than 15% at term. The accuracy of Combs's and Shinozuka's volumetric formulas
      varied least by menstrual age. Hadlock's formula underestimated preterm fetal
      weight by up to 7% and overestimated fetal weight at term by up to 5%.
      CONCLUSIONS: The accuracy of sonographic fetal weight estimation based on
      volumetric formulas is more consistent across menstrual ages than are other
      methods.

PMID- 11948570
TI  - Contrast-enhanced endosonography for the diagnosis of anal and anovaginal
      fistulas.
AB  - PURPOSE: We assessed whether contrast-enhanced anal endosonography (AES) with
      hydrogen peroxide improves the identification of anal fistulas and their internal
      openings compared with non-contrast AES. METHODS: The study group comprised 12
      patients who had various types of anal fistulas with visible external openings.
      AES was performed before and about 15 seconds after injection of 1 ml of 3%
      hydrogen peroxide into the fistula tract through the external opening. RESULTS:
      Both contrast and non-contrast AES revealed 7 transsphincteric, 2
      intersphincteric, 1 suprasphincteric, and 2 anovaginal fistulas. Simple tracts
      were found in 8 cases and complex tracts in 4 cases on non-contrast AES. Contrast
      enhanced AES revealed 9 simple and 3 complex fistulas. One fistula that appeared
      complex on the non-contrast study appeared simple after contrast agent
      administration. Contrast-enhanced AES demonstrated more internal openings than
      non-contrast AES did. Surgery confirmed 11 of the fistulas; an internal opening
      could not be located surgically for the other tract. CONCLUSIONS: Contrast
      enhanced AES appears to be superior to non-contrast AES in the preoperative
      assessment of anal and anovaginal fistulas and in demonstrating and locating
      their internal openings.

PMID- 11948571
TI  - Technique of color Doppler quantification of vascularity in transplanted kidneys.
AB  - A new technique for the quantification of vascularity based on the analysis of
      color Doppler images is described. We utilized velocity information obtained
      directly from cineloops transferred to a computer for off-line analysis. This
      methodology was used in transplanted kidneys to assess parenchymal vascularity on
      the basis of percentage color pixel density and mean flow velocity in mid-kidney
      cross-sectional regions of interest and the distance from the most peripheral
      color pixels to the capsule of the kidney. Other color Doppler quantitative
      methods have lacked reproducibility, and therefore before evaluation of the
      clinical usefulness of this technique, intraobserver reproducibility and
      interobserver reliability were assessed in 42 patients; no statistically
      significant variation was demonstrated. In 13 patients with normally functioning
      transplants, the mean maximum color pixel density was 34.7+/-13.4%, the mean flow
      velocity was 5.2+/-0.9 cm/second, and the mean distance to the capsule was 3.3+/
      1.1 mm.

PMID- 11948572
TI  - Sonographically guided arterial blood sampling using a handheld Doppler device.
AB  - The purpose of this study was to evaluate the efficacy of a commercially
      available handheld Doppler device for sonographic guidance during arterial blood
      sampling in patients whose veins are inaccessible and whose arterial pulses are
      indistinct on palpation. From September 2000 through February 2001, blood samples
      were obtained from the brachial arteries of 20 patients ranging in age from 60 to
      85 years. A commercially available continuous-wave, handheld Versadopp 10 Doppler
      device with a 10-MHz transducer, connected to a stethoscope, was aligned over
      each patient's brachial artery and used to determine the point of maximum flow.
      The blood-collection needle was inserted into the skin and advanced toward the
      point of maximum flow. Arterial blood samples were successfully obtained with no
      more than 2 passes in each patient. Sampling was unsuccessful in 2 patients;
      blood was obtained, however, from the contralateral brachial artery in both
      patients. This Doppler tool is convenient and easy to use and is helpful for
      obtaining arterial blood samples from obese or edematous patients whose veins
      cannot be accessed and who have weak, indistinct arterial pulses.

PMID- 11948573
TI  - First-trimester obstetric emergencies: spectrum of sonographic findings.

PMID- 11948574
TI  - Renal fungal ball: an unusual sonographic finding.
AB  - Fungal infections of the urinary tract tend to occur in the drainage structures
      instead of the renal parenchyma. In patients with systemic candidiasis, the
      kidney is vulnerable to the formation of cortical abscesses or obstructive
      intrarenal masses ("fungal balls"), usually at the ureteropelvic junction. We
      describe the case of a boy who presented with dysuria, fever, and chills.
      Sonographic examination showed mild enlargement of both kidneys and moderate
      dilatation of the pelvicaliceal system bilaterally. A well-defined, echogenic,
      oval, mobile mass measuring 2.5 x 2.0 cm, without posterior acoustic shadowing,
      was visualized in the pelvis of the left kidney. The upper and middle ureters
      were dilated bilaterally. A urine culture revealed hyphae of Candida albicans.
      The child received systemic antifungal therapy with fluconazole for 3 weeks.
      Follow-up sonography showed complete resolution of the mass (a fungal ball) with
      residual hydronephrosis.

PMID- 11948575
TI  - Diagnosis of malignant mesothelioma of the tunica vaginalis testis by ultrasound
      guided fine-needle aspiration.
AB  - Malignant mesothelioma of the tunica vaginalis testis is a very rare tumor that
      is not usually diagnosed until surgery is undertaken. In only a few cases has the
      correct diagnosis been obtained preoperatively by cytologic examination of fluid
      from the hydrocele. We describe a case of mesothelioma of the tunica vaginalis
      testis that was suspected on sonography because of the presence of a hydrocele
      and focal nodularities. The diagnosis was confirmed preoperatively by ultrasound
      guided fine-needle aspiration cytology aimed at 1 of the focal nodularities. Our
      patient was an 85-year-old man with concomitant cancer of the sigmoid colon;
      because of his age and the spread of his colon cancer, we did not remove the
      scrotal lesion. We recommend consideration of ultrasound-guided fine-needle
      aspiration cytology of the solid masses instead of the fluid from the hydrocele
      in cases of suspected malignant mesothelioma of the tunica vaginalis testis.

PMID- 11948576
TI  - Sonographic findings of tuberculous thyroiditis in a patient with Behcet's
      syndrome.
AB  - We report a case of tuberculous thyroiditis in a woman with Behcet's syndrome.
      The initial physical examination in May 1998 revealed multiple soft, nontender,
      mobile lymph nodes, each measuring less than 1 cm, in the left lower internal
      jugular chain. Sonography performed in February 2000 showed multiple small (< 1
      cm), oval lymph nodes, each with an intact fatty hilum, in the left lower
      internal jugular chain; the thyroid gland appeared normal. Follow-up sonography 6
      months later showed multifocal, heterogeneous, hypoechoic lesions with ill
      defined margins in both lobes of the thyroid and several small, oval lymph nodes,
      each with an intact fatty hilum, in the left lower internal jugular chain. Fine
      needle aspiration was performed on the largest thyroid lesion, and cytologic
      analysis of the aspirate revealed a small number of epithelioid histiocytes in a
      necrotic background, which was suggestive of tuberculosis. Follow-up sonography
      after 3 months of antituberculosis chemotherapy showed that the thyroid lesions
      had resolved.

PMID- 11948577
TI  - Sonographic appearance of the uterus after simple square suturing for rapid
      control of postpartum hemorrhage and preservation of fertility.
AB  - We describe the postoperative sonographic appearance of the uterus after
      successful use of simple square suturing for rapid control of profuse bleeding
      during cesarean section in a pregnant woman with uterine atony and placenta
      accreta. The serial sonograms initially showed decreased echogenicity in the
      compressed uterine area, but about 1 week after surgery, echogenicity of the
      compressed area returned to normal and, 2 weeks after surgery, patency of the
      uterine canal became evident. This report highlights the usefulness of this
      suturing technique for controlling such hemorrhage and the role of sonography in
      evaluating uterine status postoperatively.

PMID- 11948578
TI  - The SGB/NP hydration free energy model based on the surface generalized born
      solvent reaction field and novel nonpolar hydration free energy estimators.
AB  - The development and parameterization of a solvent potential of mean force
      designed to reproduce the hydration thermodynamics of small molecules and
      macromolecules aimed toward applications in conformation prediction and ligand
      binding free energy prediction is presented. The model, named SGB/NP, is based on
      a parameterization of the Surface Generalized Born continuum dielectric
      electrostatic model using explicit solvent free energy perturbation calculations
      and a newly developed nonpolar hydration free energy estimator motivated by the
      results of explicit solvent simulations of the thermodynamics of hydration of
      hydrocarbons. The nonpolar model contains, in addition to the more commonly used
      solvent accessible surface area term, a component corresponding to the attractive
      solute-solvent interactions. This term is found to be important to improve the
      accuracy of the model, particularly for cyclic and hydrogen bonding compounds.
      The model is parameterized against the experimental hydration free energies of a
      set of small organic molecules. The model reproduces the experimental hydration
      free energies of small organic molecules with an accuracy comparable or superior
      to similar models employing more computationally demanding estimators and/or a
      more extensive set of parameters.

PMID- 11948579
TI  - An ab initio theoretical study of electronic structure and properties of 2'
      deoxyguanosine in gas phase and aqueous media.
AB  - Molecular geometries of two structural forms of 2'-deoxyguanosine (keto-N9R and
      keto-N7R, R = the sugar moiety) considering both the C2'-endo and C3'-endo
      conformations of the sugar ring and those of the complexes of these species with
      two water molecules each were optimized employing the ab initio RHF procedure. A
      mixed basis set consisting of the 6-311+G* basis set for the nitrogen atom of the
      amino group and the 4-31G basis set for all the other atoms was used. The RHF
      calculations were followed by correlation correction of the total energy at the
      MP2 level. Both the structural forms of 2'-deoxyguanosine were solvated using the
      polarized continuum model (PCM) of the self-consistent reaction field (SCRF)
      theory and the corresponding RHF optimized geometries at the RHF and MP2 levels.
      Geometry optimization was also performed in aqueous media using the Onsager model
      at the RHF level using the above-mentioned mixed basis set, and subsequently,
      using the reoptimized geometries, single-point MP2 calculations were performed.
      It is found that both the keto-N9R and keto-N7R forms of 2'-deoxyguanosine as
      well as their complexes with two water molecules each would occur, particularly
      at the water-air interface. Though the normal Watson-Crick-type base pairing
      would not be possible with the keto-N7R form of 2'-deoxyguanosine(G*), two other
      (G*-C and G*-T) base pairing schemes may occur with this form of the nucleoside,
      which may cause mutation. The present calculated geometry of the keto-N9R form of
      the anti-conformation of 2'-deoxyguanosine including the dihedral angle chi(CN)
      agree satisfactorily with the available crystallographic results. The present
      results also agree satisfactorily with those obtained by other authors earlier
      for the keto-N9R form of 2'-deoxyguanosine using B3LYP and MP2 methods employing
      the 6-31G* basis set. Using transition state calculations, it is shown that
      tautomerism of guanine and other similar molecules where the tautomers would
      coexist would be facilitated by the occurrence of the H(+) and OH(-) fragments of
      water molecules. Further, this coexistence of the two tautomers appears to make
      the C8 carbon atom located between the N7 and N9 nitrogen atoms susceptible to
      attack by the OH(-) group. Thus, an explanation is obtained for the efficient
      formation of the reaction product 8-hydroxy-2'-deoxyguanosine, which serves as a
      biomarker for oxidative damage to DNA in biological systems.

PMID- 11948580
TI  - Variational treatment of the vibrational Hamiltonian for NH(3) and H(2)NO.
AB  - The full vibrational Hamiltonian for the inversion of NH(3) and H(2)NO has been
      diagonalized in a basis set that is the direct product of functions of the
      inversion coordinate and of harmonic vibrational functions independent of this
      inversion coordinate. The kinetic part of the Hamiltonian matrix is constructed
      with the use of the closure relation for these vibrational functions. The method
      is tested with the potential function which is supposed to be harmonic for the
      vibrations orthogonal to the inversion coordinate: the first computed levels are
      in good agreement with experimental levels for NH(3). For higher levels,
      anharmonic terms should be included.

PMID- 11948582
TI  - Hydrophobic similarity between molecules: a MST-based hydrophobic similarity
      index.
AB  - A similarity index based on the hydrophilic/hydrophobic properties of molecules
      is presented. Such an index is defined based on the fractional partition of the
      free energy of solvation developed within the framework of the self-consistent
      reaction field MST model, which divides the free energy of solvation or the free
      energy of transfer into contributions assigned to the surface elements defining
      the solute/solvent interface. These surface contributions can be integrated to
      derive atomic or group contributions. The suitability of the index to compute the
      molecular similarity based on hydrophobic/hydrophilic properties is examined by
      considering their application in a variety of test systems, including structure
      activity relationships, absorption properties, and molecular recognition. The
      similarity index is expected to be a very powerful tool in molecular similarity
      studies for compounds of chemical, biochemical, and pharmaceutical interest.

PMID- 11948581
TI  - Calculation of the free energy of solvation for neutral analogs of amino acid
      side chains.
AB  - The ability of the GROMOS96 force field to reproduce partition constants between
      water and two less polar solvents (cyclohexane and chloroform) for analogs of 18
      of the 20 naturally occurring amino acids has been investigated. The estimations
      of the solvation free energies in water, in cyclohexane solution, and chloroform
      solution are based on thermodynamic integration free energy calculations using
      molecular dynamics simulations. The calculations show that while the force field
      reproduces the experimental solvation free energies of nonpolar analogs with
      reasonable accuracy the solvation free energies of polar analogs in water are
      systematically overestimated (too positive). The dependence of the calculated
      free energies on the atomic partial charges was also studied.

PMID- 11948583
TI  - Comprehensive relativistic ab initio and density functional theory studies on
      PtH, PtF, PtCl, and Pt(NH(3))(2)Cl(2).
AB  - Platinum monohydride is taken as an example to compare the performance of various
      relativistic and correlation approaches, such as all-electron DPT (direct
      perturbation theory), ECP (effective core potential); RSPT2, RSPT3 (second- and
      third-order multireference Rayleigh-Schrodinger perturbation theory), CCSD(T)
      (coupled-cluster with singles, doubles, and perturbative triples), as well as the
      four-component relativistic density functional theory. It is shown that first
      order DPT performs significantly better than the (first-order) Breit-Pauli
      Hamiltonian. The performance of different approaches for the excitation energies
      of the platinum diatomics is discussed critically. The molecular spectroscopic
      constants for PtF and PtCl are predicted for the first time. The geometric data
      for several isomers of cis- and trans-Pt(NH(3))(2)Cl(2) are reported. The
      corresponding energetic data are calculated at relativistic all-electron and ECP
      CCSD(T) as well as four-component relativistic density functional levels of
      theory. Contrary to previous results, it is found that the two C(2v) isomers of
      cis-Pt(NH(3))(2)Cl(2) are marginally separated in energy, which could be ascribed
      to Cl-H interactions.

PMID- 11948584
TI  - Determination of energy minima and saddle points using multireference
      configuration interaction methods in combination with reduced gradient following:
      the S(0) surface of H(2)CO and the T(1) and T(2) surfaces of acetylene.
AB  - The implementation of the reduced gradient following (RGF) method into the
      COLUMBUS quantum-chemical program system is reported using the newly developed
      analytic MR-CISD/AQCC gradient feature. By this combination a very useful tool
      has been developed for general searches of stationary points on ground- and
      excited-state energy surfaces. This procedure is applied to the S(0) surface of
      H(2)CO and the T(1) and T(2) surfaces of acetylene. For H(2)CO we investigated
      three minima (formaldehyde, s-trans, and s-cis hydroxycarbene) and five saddle
      points. For the T(1) and T(2) states of acetylene the cis- and trans-minima and
      the planar and nonplanar saddle points were computed.

PMID- 11948586
TI  - Influence of the presence of small gas molecules in the structure of comblike
      polyacrylates: a Monte Carlo study.
AB  - A theoretical strategy has been developed to study the motion of small molecules
      through ordered polymeric systems. The strategy, which has been incorporated into
      a computer program denoted MCDP/2, is especially useful to study comblike
      polymers organized in biphasic arrangements. This is because it is based on a
      configurational bias Monte Carlo algorithm, which is more efficient than
      conventional methods to study dense systems. The MCDP/2 program has been used to
      investigate the influence of CH(4) and CO(2) gas molecules in the structure of
      isotactic poly(octadecyl acrylate), a typical comblike polymer. For this purpose,
      the pure polymer and different molecular systems constituted by several gas
      molecules dissolved in the polymer matrix have been simulated. Results indicated
      that the structural relaxation of the polymer is not coupled to the motion of gas
      molecules. The importance of these results in the field of molecular modeling of
      transport properties in comblike polymers is discussed.

PMID- 11948587
TI  - A new molecular mechanics force field for the oxidized form of blue copper
      proteins.
AB  - A molecular mechanics force field for blue copper proteins has been developed,
      based on a rigid potential energy surface scan of the Cu(II)/His/His/Cys/Met
      chromophore, using DFT (B3LYP) calculations and the AMBER force field for the
      protein backbone. The strain-energy-minimized structures of the model chromophore
      alone are in excellent agreement with the DFT-optimized structure, and those of
      the entire set of cupredoxins (five structures are considered) are, within the
      experimental error limits, in good agreement with the single crystal structural
      data. However, the structural variation in the computed structures is much
      smaller than those in the experimental structures. It is shown that, due to the
      large error limits in the experimental data, a validation of the force field with
      experimental structural data is impossible because, within the error limits, all
      experimental structures considered are virtually identical. A validation on the
      basis of spectroscopic data and their correlation with experimental and computed
      structural data is proposed, and, as a first example, the correlation of
      intensity ratios of the charge transfer transitions with a specific distortion
      mode is presented. The quality of the correlation, using the computed structures,
      is higher than that with the X-ray structures, and this indicates that the
      computed structures are meaningful.

PMID- 11948588
TI  - New approach to free energy of solvation applying continuum models to molecular
      dynamics simulation.
AB  - A new approach to the calculation of the free energy of solvation from
      trajectories obtained by molecular dynamics simulation is presented. The free
      energy of solvation is computed as the sum of three contributions originated at
      the cavitation of the solute by the solvent, the solute-solvent nonpolar
      (repulsion and dispersion) interactions, and the electrostatic solvation of the
      solute. The electrostatic term is calculated based on ideas developed for the
      broadly used continuum models, the cavitational contribution from the excluded
      volume by the Claverie-Pierotti model, and the Van der Waals term directly from
      the molecular dynamics simulation. The proposed model is tested for diluted
      aqueous solutions of simple molecules containing a variety of chemically
      important functions: methanol, methylamine, water, methanethiol, and
      dichloromethane. These solutions were treated by molecular dynamics simulations
      using SPC/E water and the OPLS force field for the organic molecules. Obtained
      free energies of solvation are in very good agreement with experimental data.

PMID- 11948590
TI  - Rb(+)/Cs(+) selectivity of benzo and tribenzo derivatives of the 21C7 crown
      ether. A density functional study.
AB  - A density functional study has been performed on Rb(+) and Cs(+) complexes of
      mono and tribenzo derivatives of the 21Crown7 crown ether. Calculations have been
      carried out using the B3LYP functional together with a split valence basis set
      with additional polarization and diffuse functions. The cations have been
      described with effective core potentials. Structures of the tribenzo-21Crown7 are
      compared to X-ray data. The Rb(+)/Cs(+) affinity of the benzo and tribenzo
      derivatives in gas phase is discussed on the basis of binding energies, strain
      energies, and electrostatic contributions. For the first time, a detailed
      description of the effect arising from the presence of benzo groups is described.
      On one hand, the benzo groups decrease the electronic density on the ether oxygen
      atoms. On the other hand, they confer a stronger electronic polarizability to the
      ligand. The energetic analysis shows that the polarization contributions play a
      crucial role and reach up to 29% of the total electrostatic energy.

PMID- 11948589
TI  - Energy-based reconstruction of a protein backbone from its alpha-carbon trace by
      a Monte-Carlo method.
AB  - An automatic procedure is proposed for reconstruction of a protein backbone from
      its C(alpha)-trace; it is based on optimization of a simplified energy function
      of a peptide backbone, given its alpha-carbon trace. The energy is expressed as a
      sum of the energies of interaction between backbone peptide groups that are not
      neighbors in the sequence, the energies of local interactions within all amino
      acid residues, and a harmonic penalty function accounting for the conservation of
      standard bond angles. The energy of peptide group interactions is calculated
      using the assumption that each peptide group acts as a point dipole. For local
      interaction energy, use is made of a two-dimensional Fourier series expansion of
      the energies of model terminally blocked amino acid residues, calculated with the
      Empirical Conformational Energy Program for Peptides (ECEPP/3) force field in the
      angles lambda((1)) and lambda((2)) defining the rotation of peptide groups
      adjacent to a C(alpha) carbon atom about the corresponding C(alpha) em leader
      C(alpha) virtual-bond axes. To explore all possible rotations of peptide groups
      within a fixed C(alpha)-trace, a Monte Carlo search is carried out. The initial
      lambda angles are calculated by aligning the dipoles of the peptide groups that
      are close in space, subject to the condition of favorable local interactions.
      After the Monte Carlo search is accomplished with the simplified energy function,
      the energy of the structure is minimized with the ECEPP/3 force field, with
      imposition of distance constraints corresponding to the initial C(alpha)-trace
      geometry. The procedure was tested on model alpha-helices and beta-sheets, as
      well as on the crystal structure of the immunoglobulin binding protein (PDB code:
      1IGD, an alpha/beta protein). In all cases, complete backbone geometry was
      reconstructed with a root-mean-square (rms) deviation of 0.5 A from the all-atom
      target structure.

PMID- 11948591
TI  - Role of bifurcation in the bond shifting of cyclooctatetraene.
AB  - The present study of the cyclooctatetraene potential energy surface shows the
      presence of a bifurcation (valley ridge inflection point) in the intrinsic
      reaction coordinate path between the two transition states of D(8h) and D(4h)
      symmetries. This result is of capital importance for the correct understanding of
      the bond shifting and ring inversion processes in this compound.

PMID- 11948592
TI  - A fast pairwise evaluation of molecular surface area.
AB  - A fast and general analytical approach was developed for the calculation of the
      approximate van der Waals and solvent-accessible surface areas. The method is
      based on three basic ideas: the use of the Lorentz transformation formula, a
      rigid-geometry approximation, and a single fitting parameter that can be refitted
      on the fly during a simulation. The Lorentz transformation equation is used for
      the summation of the areas of an atom buried by its neighboring contacting atoms,
      and implies that a sum of the buried pairwise areas cannot be larger than the
      surface area of the isolated spherical atom itself. In a rigid-geometry
      approximation we numerically calculate and keep constant the surface of each atom
      buried by the atoms involved in 1-2 and 1-3 interactions. Only the contributions
      from the nonbonded atoms (1-4 and higher interactions) are considered in terms of
      the pairwise approximation. The accuracy and speed of the method is competitive
      with other pairwise algorithms. A major strength of the method is the ease of
      parametrization.

PMID- 11948593
TI  - Generate: a program for 3-D structure generation and conformational analysis of
      peptides and peptidomimetics.
AB  - The program Generate, aimed at generating 3-D structures for peptides and
      peptidomimetics, is presented. The algorithm is based on a build-up procedure,
      using a library of conformations of amino acid residues. This library is built
      from conformational analysis of amino acids placed in a di- or tripeptide
      environment to mimic the surroundings of the amino acid in a true peptide,
      considering different positions of the residue in the peptide chain (peptidyl
      fragment, NH(+)(3)-terminus or COO(-)-terminus). Cis-trans isomerism in the amide
      bonds is taken into account by construction of rotamer libraries for different
      isomers. Water solvation is included through the GB/SA model. New amino acid
      residues can easily be added to the libraries, making it possible to generate
      conformations of peptidomimetics.

PMID- 11948594
TI  - Assessment of the parallelization approach of d2_cluster for high-performance
      sequence clustering.
AB  - The exponential increase in expressed sequence tag (EST) sequence data amplifies
      the computational cost of clustering sequences such that new algorithms are
      required to analyze data at a greater rate. We have parallelized d2_cluster on a
      SGI Origin 2000 multiprocessor and observed a speedup of approximately 100x on
      126 processors when processing a 15,876 EST dataset. The parallelized d2_cluster
      code is obtainable from the SANBI website (http://www.sanbi.ac.za/CODES).

PMID- 11948595
TI  - Histologic analysis of the effect on dental pulp of a 9.6-microm CO(2) laser.
AB  - BACKGROUND AND OBJECTIVE: Both patients and dentists would like a replacement of
      the dental drill. During the last decade, lasers have been investigated as a
      possible replacement. For lasers to be accepted, studies must show that their
      effect on the dental pulpal tissues is equal to or less noxious than those
      effects caused by the dental handpiece (drill). STUDY DESIGN/MATERIALS AND
      METHODS: In this study, two laser systems were used; the first was a breadboard
      CO(2) laser and the second a prototype clinical CO(2) laser system both emitted
      60-micros-long pulses of 9.6-microm radiation. On the delivery system of both
      lasers, a scanner moved the focussed beam in a circular pattern and a water spray
      system served to cool the ablation site. Both lasers were used to create holes of
      similar dimensions in canine teeth. The treated teeth were then restored and
      harvested at either 4 days or 4 weeks. The teeth were decalcified, sectioned, and
      stained for examination via light microscopy. RESULTS: The histologic examination
      revealed normal pulpal tissues in the canine teeth treated with both CO(2)
      lasers. Some histologic sections showed an increase in the predentin layer, 28
      days after laser treatment. While many histologic sections showed normal pulpal
      architecture following handpiece treatment, some sections showed total disruption
      of the normal pulpal histology. CONCLUSIONS: Histologic evaluation revealed that
      the lasers produced no noticeable damage to the dental pulpal tissue and appear
      to be a safe method for removing dental hard tissues. From this study, it appears
      that 9.6 microm CO(2) laser does not cause damage to the dental pulpal tissues in
      dogs.

PMID- 11948596
TI  - Adhesion of Er:YAG laser-irradiated dentin and composite resins: application of
      various treatments on irradiated surface.
AB  - BACKGROUND AND OBJECTIVES: The investigation of adhesion between an Er:YAG laser
      irradiated surface and composite resin is very important to ensure the best
      clinical results. The purpose of this investigation is to determine if the
      application of various treatments on Er:YAG laser-irradiated dentin surface
      affects the tensile bond strength between dentin and composite resins. STUDY
      DESIGN/MATERIALS AND METHODS: In this investigation, the application of
      phosphoric acid, ultrasonic scaler, air-scaler, and air-powder polisher were
      tested as techniques to increase the bond strength of composite resins to Er:YAG
      laser-irradiated dentin surface. RESULTS: The tensile bond strength of the air
      powder polished group was highest, at 18.45 +/- 3.72 MPa, and the lowest value
      was that of the only laser-irradiated group, at 12.56 +/- 4.38 MPa. CONCLUSIONS:
      The bond strengths in treated with air-powder polished group and phosphoric acid
      etched group were significantly higher than that of the group in laser
      irradiation alone.

PMID- 11948597
TI  - Photodynamic therapy of vulvar and vaginal condyloma and intraepithelial
      neoplasia using topically applied 5-aminolevulinic acid.
AB  - BACKGROUND AND OBJECTIVES: To determine the feasibility of photodynamic therapy
      (PDT) of vulvar and vaginal condyloma and intraepithelial neoplasia (VIN, VAIN)
      and to compare PDT results with conventional treatments. STUDY DESIGN/MATERIALS
      AND METHODS: Thirty-eight patients with vulvar or vaginal intraepithelial
      neoplasia (VIN) grade II/III (n = 22) or condyloma (n = 16) had 10% 5
      aminolevulinic acid (ALA)-gel applied topically. After 2-4 hours, 80-125 J/cm(2)
      laser light at a wavelength of 635 nm was applied. PDT was compared to
      conventional treatments for condyloma (CO(2) laser evaporation) and for VIN III
      (laser evaporation, surgical excision). RESULTS: The complete clearance rate for
      condyloma treated by PDT was 66% and the rate for IN was 57% (as determined by
      biopsy). Of the neoplasia patients, none with hyperkeratotic VIN (n = 4)
      responded, and only one of four with increased pigmentation cleared. No scarring
      occurred, and postoperative discomfort lasted 4.9 +/- 3.4 days. Reduced disease
      free survival (DFS) was associated with multifocal VIN (P = 0.02, OR 2.17, 95% CI
      1.15-4.08), but DFS did not vary with treatment mode. CONCLUSIONS: Although PDT
      is not equally efficacious for all subgroups, PDT for condyloma and
      intraepithelial neoplasia appears to be as effective as conventional treatments,
      but with shorter healing time and excellent cosmetic results.

PMID- 11948598
TI  - Laser induced thermotherapy (LITT) of experimental liver metastasis-detection of
      residual tumors using Gd-DTPA enhanced MRI.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the accuracy of
      Gd-DTPA MRI in the detection of recurrent tumor after laserinduced thermotherapy
      (LITT) of experimental liver metastases. STUDY DESIGN/MATERIALS AND METHODS: LITT
      was performed at different energy levels in VX-2 tumor-bearing rabbits (n = 80).
      MRI and histology were placed at 0, 24, 96 hours, and 14 days. Signal intensities
      were calculated of the transition between thermally damaged and undamaged tissue
      (transition zone = TZ) and of the surrounding tissue (reference zone = RZ).
      RESULTS: Tumor recurrence was seen in 47 animals. At 24 hours sensitivity,
      specificity and accuracy was 92, 100, and 95% in TZ and 23, 100, and 50% in RZ.
      At 14 days sensitivity, specificity and accuracy was 100, 11, and 60% in TZ and
      100, 89, and 95% in RZ. CONCLUSIONS: Recurrence is best excluded in TZ at 24 hour
      and in RZ at 14 day with an accuracy up to 95%.

PMID- 11948599
TI  - Correlation between near-infrared Raman spectroscopy and the histopathological
      analysis of atherosclerosis in human coronary arteries.
AB  - BACKGROUND AND OBJECTIVES: Modern diagnostic methods such as near-infrared Raman
      spectroscopy (NIRS) allow quantification and evaluation of human atherosclerotic
      lesions, which can be useful in diagnosing coronary artery disease. The objective
      of the present study is to obtain feasible diagnostic information to detect
      atheromatous plaque using NIRS combined with discriminant analysis. STUDY
      DESIGN/MATERIAL AND METHODS: An 830 nm Ti: sapphire laser pumped by an argon
      laser provides near-infrared excitation. A spectrograph disperses light scattered
      from arterial tissue and a liquid-nitrogen cooled CCD detects the Raman spectra.
      A total of 111 arterial fragments were scanned and Raman results were compared
      with histopathology. Principal components analysis (PCA) and Mahalanobis distance
      (m-distance) were used to model an algorithm for tissue classification into three
      categories: non-atherosclerotic (NA), non-calcified (NC), and calcified (C) using
      Raman spectra. Spectra were randomly separated into training and prospective
      groups. RESULTS: It has been found that, for the NA tissue, the algorithm has
      sensitivity of 84 and 78% and specificity of 91 and 93% for training and
      prospective groups, respectively. For the NC tissue the algorithm has sensitivity
      of 88 and 90% and specificity of 88 and 83%. For the C tissue both sensitivity
      and specificity were maximum, 100%. CONCLUSIONS: An algorithm using PCA and
      discriminant analysis based on m-distance has been developed and successfully
      applied to diagnose coronary artery disease by NIRS obtaining good sensitivity
      and specificity for each tissue category.

PMID- 11948600
TI  - Full-face photorejuvenation of photodamaged skin by intense pulsed light with
      integrated contact cooling: initial experiences in Asian patients.
AB  - BACKGROUND AND OBJECTIVES: For Asian skin, recent "non-ablative" skin
      rejuvenation techniques have become the focus of attention for darker complected
      patients. In our earlier research, we have shown that intense pulsed light (IPL)
      technology can be applied to Asian skin with a high degree of safety and
      efficacy. In this study, we performed full-face photorejuvenation using a new IPL
      device incorporating a 560 nm filter and integrated contact cooling system for
      the improvement of various symptoms associated with photoaging in Asian patients.
      STUDY DESIGN/MATERIALS AND METHODS: A total of 73 patients were treated with a
      series of five or more full-face treatments at 3-4 week intervals using IPL with
      integrated contact cooling. One month after the third and fifth treatments, the
      patient and the treating physicians subjectively evaluated improvement in five
      areas-in pigmentation, telangiectasia, fine wrinkles, skin texture, and over-all
      improvement. In addition, histological changes were evaluated. RESULTS:
      Pigmentation improvement, telangiectasia reduction, fine wrinkle reduction,
      smoother skin texture, and over-all improvement were evaluated according to five
      grades of percentage improvement. In addition, the subjective rating by the
      patients and the physicians was averaged, and the combined results were
      evaluated. After the fifth treatment, a combined rating of greater than 60%
      improvement was given to more than 80% of patients for pigmentation improvement,
      telangiectasia reduction or removal, smoother skin texture, and overall
      improvement. Histological evaluations showed strong staining of Type I and Type
      III collagen. Complications were minor and transitory, with burning sensations
      and erythema in only two patients. CONCLUSION: Full-face photorejuvenation for
      Asian patients using this device is not only effective but is also associated
      with fewer post-treatment complications than other more invasive modalities. We
      conclude that IPL photorejuvenation can be the basis for safe and effective skin
      rejuvenation in Asian patients.

PMID- 11948601
TI  - Measurement of the binding forces between von Willebrand factor and variants of
      platelet glycoprotein Ibalpha using optical tweezers.
AB  - BACKGROUND AND OBJECTIVE: Thrombus formation is initiated by adhesion of the
      platelet receptor, glycoprotein (GP) Ib-IX-V complex, to its adhesive ligand, von
      Willebrand factor (vWf), in the subendothelium or plasma. The vWf-binding domain
      of GP Ib-IX-V is in the GP Ibalpha subunit of the complex and contains a leucine
      rich repeat region. The adhesion of different leucine-rich repeats was studied
      using optical tweezers in order to determine which ones were critical for the
      vWf/GP Ibalpha interaction. STUDY DESIGN/MATERIALS AND METHODS: Canine GP Ibalpha
      does not normally bind to human vWf, and thus canine-human GP Ibalpha chimeras
      were constructed by sequentially replacing human GP Ibalpha structural regions
      with their canine counterparts. Chinese hamster ovary (CHO) cells, which are
      frequently used to express platelet GP complexes, were transfected with the
      chimeric proteins. Optical tweezers (lambda = 830 nm) were used to investigate
      bond strengths between vWf and different GP Ibalpha canine-human chimeras. Since
      vWf does not bind GP Ibalpha without high shear stress, the compounds botrocetin
      and ristocetin were used to induce binding between human vWf and the chimeras.
      RESULTS: All human-canine GP Ibalpha chimeras bound to vWf in the presence of
      botrocetin. Replacement of the N-terminal flanking sequence and the first leucine
      rich repeat resulted in lower GP Ibalpha/vWf bond strengths than the wild-type
      human GP Ibalpha/vWf bond strength (P < 0.05). Chimeras lacking the second
      leucine-rich repeat did not adhere to vWf with ristocetin acting as modulator.
      CONCLUSION: The N-terminal flanking sequence and the first leucine-rich repeat of
      GP Ibalpha were found to be important but not necessary for GP Ibalpha to adhere
      to vWf. The second leucine-rich repeat was found to be critical for GP Ibalpha to
      bind vWf and could potentially be used in the development of a novel recombinant
      anti-thrombotic drugs.

PMID- 11948602
TI  - Enhanced adenoviral-vector mediated gene transfer using human albumin solder.
AB  - BACKGROUND AND OBJECTIVE: Laser tissue welding with human albumin solder (HAS)
      has been used as an alternative method of wound closure. Adenoviral vectors have
      been used to introduce various cytokine genes into wounds to accelerate wound
      closure. In the present study, we were interested in the effect of HAS on
      adenoviral vector transfer of the beta-galactosidase (beta-gal) gene in vitro and
      in vivo. STUDY DESIGN/MATERIALS AND METHODS: 3T3 fibroblasts were used to study
      the effect of HAS on beta-gal gene transfer in vitro. The presence of beta-gal
      was determined by Western blot, and its activity by a colorimetric assay. A punch
      biopsy model of wound healing in pigs was used for in vivo experiments. RESULTS:
      HAS increased the efficiency of adenoviral-mediated beta-gal transduction and
      stabilized the adenovirus at room temperature. HAS protected adenovirus from
      inactivation by laser, both in vitro and in vivo. CONCLUSIONS: HAS may stabilize
      adenoviral vectors to deliver cytokine genes in future wound healing experiments.

PMID- 11948603
TI  - Effects of exposure to low level radiofrequency fields on acetylcholine release
      in hippocampus of freely moving rats.
AB  - Some central cholinergic effects have been reported in animals after acute
      exposure to radiofrequency electromagnetic field at low intensity. We studied
      acetylcholine (ACh) release in the brain of freely moving rats exposed for 1 h
      during the day to a 2.45 GHz continuous wave radiofrequency field (RF) (2 or 4
      mW/cm(2)) or exposed for 1 or 14 h during the night to a 800 MHz field modulated
      at 32 Hz (AM 200 mW/cm(2)). Measurements were performed by microdialysis using a
      membrane implanted through the upper CA1 region of the hippocampus. After
      irradiation with the 2.45 GHz RF, rats exposed at 2 mW/cm(2) did not show a
      significant modification of Ach release, whereas those exposed at 4 mW/cm(2)
      showed a significant 40% decrease in mean ACh release from hippocampus. This
      decrease was maximal at 5 h post exposure. Exposure to the 800 MHz RF for 1 h did
      not cause any significant effect, but exposure for 14 hrs induced a significant
      43% decrease in ACh release during the period 11 p.m.-4 a.m. compared to control
      rats. In the control group we observed an increase of ACh release at the
      beginning of the night, which was linked to the waking period of rats. This
      normal increase was disturbed in rats exposed overnight to the 800 MHz RF. This
      work indicates that neurochemical modification of the hippocampal cholinergic
      system can be observed during and after an exposure to low intensity RF.

PMID- 11948604
TI  - Study of thermal effects of ultrasound stimulation on fracture healing.
AB  - Low intensity ultrasound stimulation has been used as a strategy to promote
      fracture healing. This study investigated the mechanism of ultrasound stimulation
      in enhancing fracture healing. Forty-five adult New Zealand White rabbits were
      divided into control, microwave treated, and ultrasound stimulation groups. After
      anesthesia, transverse osteotomy was created at midportion of the fibula bone.
      Intravital staining followed by fluorescence microscopic examination of new bone
      formation in the osteotomy site and biomechanical tests on torsional stiffness of
      the osteotomy site were performed. The difference between each examination was
      evaluated and analyzed. After ultrasound stimulation, new bone formation in the
      osteotomy site of the stimulated limb was 23.1-35.8% faster than that of the sham
      treated limb; the torsional stiffness of the stimulated limb was 44.4-80.0%
      higher than that of the sham treated limb. In the group of microwave hyperthermia
      treatment, the new bone formation was higher than that of the sham treated limb,
      but the difference was not statistically significant. The difference in torsional
      stiffness between the microwave hyperthermia treated limbs and the sham treated
      limb was not quite statistically significant. We demonstrated that low intensity
      ultrasound stimulation could increase the new bone formation and torsional
      stiffness. These effects probably are not mediated via hyperthermia.

PMID- 11948605
TI  - Hypersensitivity symptoms associated with exposure to cellular telephones: no
      causal link.
AB  - The hypothesis that there exist hypersensitive persons who perceive subjective
      symptoms from radiofrequency (RF) fields emitted by hand held mobile phones
      (cellular phones) was tested using double blind provocation experiments. We also
      tested whether sensitive subjects are able to determine whether the phone is on
      or off by sensing RF fields. The study group consisted of 20 volunteers (13 women
      and 7 men) who reported themselves as being sensitive to cellular phones. The RF
      exposure sources were one analogue NMT phone (900 MHz) and two digital GSM phones
      (900 and 1800 MHz). The duration of a test session was 30 min, and three or four
      sessions were performed in random order for each subject during 1 day. The
      subjects were asked to report symptoms or sensations as soon as they perceived
      any abnormal feelings. In addition, the subjects' blood pressure, heart rate, and
      breathing frequency were monitored every 5 min. The results of the study
      indicated that various symptoms were reported, and most of them appeared in the
      head region. However, the number of reported symptoms was higher during sham
      exposure than during real exposure conditions. In addition, none of the test
      persons could distinguish real RF exposure from sham exposure. Hence, we conclude
      that adverse subjective symptoms or sensations, though unquestionably perceived
      by the test subjects, were not produced by cellular phones.

PMID- 11948606
TI  - NF-kappaB DNA-binding activity after high peak power pulsed microwave (8.2 GHz)
      exposure of normal human monocytes.
AB  - The hypothesis investigated is that exposure of a mammalian cell to high peak
      power pulsed RF, at the frequency of 8.2 GHz, can result in the activation of an
      important eukaryotic transcriptional regulator, nuclear factor kappa B (NF
      kappaB). This DNA-binding protein controls genes involved in long term cellular
      regulation. The selection of 8.2 GHz was based on the availability of a high peak
      power pulsed RF transmitter. In these studies, triplicate cultures of human
      monocytes (Mono Mac-6) were exposed to the pulsed wave radiation. The peak to
      average power ratio was 455:1 (2.2 micros pulse width and pulse repetition rate
      of 1000 pulses/s). The average power density at the position of exposure was 50
      W/m(2), and the mean SAR at the bottom of the culture flask was 10.8 +/- 7.1
      W/kg. The FDTD analysis indicated that 10% of the cells had an SAR of 22-29 W/kg.
      The cells were exposed continuously for 90 min at 37 degrees C, reincubated at
      this temperature, and harvested 4 h postexposure. The nuclear extracts were
      analyzed by electrophoretic mobility shift assay. The results showed a profound
      increase (3.6-fold) in the DNA binding activity of NF-kappaB in monocytes at 4 h
      after the pulsed RF exposure compared to sham irradiated controls. Competition
      experiments with cold NF-kappaB- specific oligonucleotides confirmed the
      specificity of the DNA binding activity. These results provide evidence that high
      peak power pulsed radiofrequency radiation can perturb the cell and initiate cell
      signaling pathways. However, at this point, we are not prepared to advocate that
      the cause is a nonthermal mechanism. Because of the broad distribution of SAR's
      in the flask, experiments need to be performed to determine if the changes
      observed are associated with cells exposed to high or low SARs.

PMID- 11948607
TI  - Proposed test for detection of nonlinear responses in biological preparations
      exposed to RF energy.
AB  - Demodulation of amplitude modulated radio frequency (RF) energy has been proposed
      as a mechanism for the biological responses to these fields. The experiment
      proposed here tests whether the electric and magnetic structures of biological
      cells exhibit the nonlinear responses necessary for demodulation. A high Q cavity
      and very low noise amplification can be used to detect ultraweak nonlinear
      responses that appear as a second harmonic of a RF field incident on the sample.
      Nonlinear fields scattered from metabolically active biological cells grown in
      monolayer or suspended in medium can be distinguished from nonlinearities of the
      apparatus. Estimates for the theoretical signal sensitivity and analysis of
      system noise indicate the possibility of detecting a microwave signal at 1.8 GHz
      (2nd harmonic of 900 MHz) as weak as one microwave photon per cell per second.
      The practical limit, set by degradation of the cavity Q, is extremely low
      compared to the much brighter thermal background, which has its peak in the
      infrared at a wavelength of about 17 microm and radiates 10(10) infrared photons
      per second per cell in the narrow frequency band within 0.5% of the peak. The
      system can be calibrated by introduction of known quantities of nonlinear
      material, e.g., a Schottky diode. For an input power of 160 microW at 900 MHz
      incident on such biological material, the apparatus is estimated to produce a
      robust output signal of 0.10 mV at 1.8 GHz if detected with a spectrum analyzer
      and a 30-dB gain low noise amplifier. The experimental threshold for detection of
      nonlinear interaction phenomena is 10(10) below the signal produced by a Schottky
      diode, giving an unprecedented sensitivity to the measurement of nonlinear energy
      conversion processes in living tissue.

PMID- 11948608
TI  - Comparison of three different ways of measuring distances between residences and
      high voltage power lines.
AB  - The aim of this study was to evaluate whether distance data based on calculations
      by use of digitalized geographical information systems (GIS) and distance data
      based on measurements on 1:5000 maps agree sufficiently with on site distance
      measurements to be used as input to magnetic field calculations in
      epidemiological studies. The analysis were performed by use of weighted kappa
      (kappa(w)) statistical method described by Bland and Altman for comparison of
      measures of agreement. Map measurements showed better agreement with on site
      measurements than GIS calculations did. However, we consider both methods
      appropriate for use in larger epidemiological studies if the results are
      interpreted with caution. GIS calculations have the advantage of being both time
      and cost saving.

PMID- 11948609
TI  - 50 Hz magnetic fields of varying flux intensity affect cell shape changes in
      invertebrate immunocytes: the role of potassium ion channels.
AB  - The effect induced by exposure to 50 Hz magnetic fields (MFs) in immunocytes from
      the mussel Mytilus galloprovincialis is evaluated. The whole animal was exposed
      for 15 and 30 min to MF intensities ranging from 200 to 1,000 microT. The changes
      in the cellular shape of immunocytes, expressed as shape factor (SF), were
      studied at different times after addition of the chemotacting substance N-formyl
      Meth-Leu-Phe (fMLP). Results show that MFs provoke differing delays in fMLP
      induced cellular shape changes: 200 microT are ineffective, while levels from 300
      microT upwards cause a significant increase in immunocyte SF values compared to
      controls. Reactivation of the cells is possible up to an intensity of 600 microT.
      The use of PCO 400, an opener of ATP-sensitive K+ channels, shows that potassium
      channels are involved in the effect of MFs on M. galloprovincialis immunocytes.

PMID- 11948610
TI  - Effects of extremely low frequency (50 Hz) magnetic field on morphological and
      biochemical properties of human keratinocytes.
AB  - We investigated the effects on human keratinocytes (HaCaT) of exposure to a
      sinusoidal magnetic field of 2 mT (50 Hz). These cells are a good model for
      studying interaction of nonionising radiation, because they are not shielded from
      fields in vivo and also because they are resistant to both mechanical and thermal
      stimuli. We performed scanning microscopy which showed modification in shape and
      morphology in exposed cells. This modification is related to differential actin
      distribution as revealed by phalloidin fluorescence analysis. Moreover, the
      exposed cells show increased clonogenic capacity, as well as increased cellular
      growth as showed by clonogenicity assays and growth curves. Indirect
      immunofluorescence analysis using a fluorescent antibody against involucrin and
      beta4 integrin, which are respectively differentiation and adhesion markers,
      revealed an increase of involucrin expression and segregation of beta4 integrin
      in the cell membrane in cells exposed to 50 Hz; a higher percentage of the
      exposed cells shows a modified pattern of adhesion and differentiation markers.
      We also present evidence that exposure of HaCaT cells can interfere with protein
      kinase activity. Our observations confirm the hypothesis that electromagnetic
      fields at 50 Hz may modify cell membrane morphology and interfere with initiation
      of the signal cascade pathway and cellular adhesion.

PMID- 11948611
TI  - Effect of magnetic field exposure on calcium channel currents using patch clamp
      technique.
AB  - Calcium influxes through the membrane of PC-12D cells were measured under
      exposure to DC biased AC magnetic fields in resonant conditions of the ion
      cyclotron and the ion parametric resonance hypotheses and compared with influxes
      in cells without exposure to the magnetic field. After cancellation of the
      geomagnetic field, the cells were exposed to the horizontal fields generated by a
      current sheet, a planar sheet of conductor which generated a satisfactorily
      homogeneous horizontal magnetic field on the stage of a microscope without
      hindering treatment of a cell under observation. At or near any resonant
      conditions, no change in calcium influx could be detected under standard patch
      clamp conditions.

PMID- 11948612
TI  - Factors confounding cytosolic calcium measurements in Jurkat E6.1 cells during
      exposure to ELF magnetic fields.
AB  - Reported changes in the cytosolic calcium concentration ([Ca2+](c)) as a result
      of exposure to extremely low frequency (ELF) magnetic fields (MF) have been
      equivocal. In this study, we examine the possibility that some of these
      differences are attributable to variability associated with the cell cycle, pH of
      the suspension medium, and response to a calcium agonist. We used a custom
      designed spectrofluorimeter to measure [Ca2+](c) in Indo 1-AM loaded Jurkat E6.1
      cells suspended in conditioned RPMI 1640 medium containing 10% fetal bovine
      serum. Four exposures were examined: zero static MF (Null), 60 Hz 100
      microT(peak) sinusoidal MF (AC), 78 microT static MF (DC), and the combination of
      the 60 Hz and the 78 microT static MF (AD + DC). A significant decrease in
      normalized [Ca2+](c) values between 375-495 s for the DC and AC + DC groups was
      found in comparison to the Null group. However, statistical analysis indicated
      that cell cycle and quality of the alpha-CD3 monoclonal antibody response were
      significant covariates, while pH was not a significant covariate. When the effect
      of these covariates was taken into account, all exposure groups were
      significantly different from the control. Our results suggest that ELF MF effects
      may not be seen unless correction is made for biological variability of each cell
      preparation with respect to cell cycle and [Ca2+](c) response to antigen
      stimulation.

PMID- 11948613
TI  - Bacterial actins? An evolutionary perspective.
AB  - According to the conventional wisdom, the existence of a cytoskeleton in
      eukaryotes and its absence in prokaryotes constitute a fundamental divide between
      the two domains of life. An integral part of the dogma is that a cytoskeleton
      enabled an early eukaryote to feed upon prokaryotes, a consequence of which was
      the occasional endosymbiosis and the eventual evolution of organelles. Two recent
      papers1, 2 present compelling evidence that actin, one of the principal
      components of a cytoskeleton, has a homolog in Bacteria that behaves in many ways
      like eukaryotic actin. Sequence comparisons reveal that eukaryotic actin and the
      bacterialhomolog (mreB protein), unlike many other proteins common to eukaryotes
      and Bacteria, have very different and more highly extended evolutionary
      histories.

PMID- 11948614
TI  - Helicase homologues maintain cytosine methylation in plants and mammals.
AB  - The Arabidopsis DDM1 gene is required for the maintenance of genomic methylation
      patterns but is a helicase homolog of the SWI2/SNF2 family rather than a DNA
      methyltransferase. Dennis et al. have shown that disruption of the mouse Lsh
      gene, the mammalian gene most closely related to DDM1, causes demethylation of
      the mouse genome. This result suggests that the mechanisms that maintain
      methylation patterns in the genomes of mammals and flowering plants are more
      conserved than previously suspected.

PMID- 11948615
TI  - DNA replication joins the revolution: whole-genome views of DNA replication in
      budding yeast.
AB  - Replication origins, which are responsible for initiating the replication of
      eukaryotic chromosomal DNAs, are spaced at intervals of 40 to 200 kb. Although
      the sets of proteins that assemble at replication origins during G(1) to form pre
      replicative complexes are highly conserved, the structures of replication origins
      varies from organism to organism. The identification of replication origins has
      been a labor-intensive task, requiring the analysis of chromosomal DNA
      replication intermediates. As a result, only a few replication origins have been
      identified and studied. In a pair of recently published papers, Raghuraman and
      colleagues and Wyrick, Aparicio and colleagues provide complementary microarray
      based approaches to the identification of replication origins. These genome-wide
      views of DNA replication in Saccharomyces cerevisiae provide new insights into
      the way that the genome is duplicated and hold promise for the analysis of other
      genomes.

PMID- 11948616
TI  - Toward reconstitution of in vivo microtubule dynamics in vitro.
AB  - The transition from interphase to mitosis is marked by a dramatic change in
      microtubule dynamics resulting in the reorganization of the microtubule network
      that culminates in mitotic spindle formation. While the molecular basis for this
      change in microtubule organization remains obscure, it is currently thought that
      a balance in the activity of microtubule stabilizing and destabilizing factors
      regulates how dynamic cellular microtubules are. By mixing the microtubule
      stabilizer XMAP215 and the microtubule destabilizer XKCM1, reconstitution of in
      vivo-like microtubule dynamics has now been achieved in vitro.

PMID- 11948617
TI  - Animal models of Parkinson's disease.
AB  - Animal models are important tools in experimental medical science to better
      understand pathogenesis of human diseases. Once developed, these models can be
      exploited to test therapeutic approaches for treating functional disturbances
      observed in the disease of interest. On the basis of experimental and clinical
      findings, Parkinson's disease (PD) was the first neurological disease to be
      modeled and, subsequently, to be treated by neurotransmitter replacement therapy.
      Agents that selectively disrupt or destroy catecholaminergic systems, such as
      reserpine, methamphetamine, 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine have been used to develop PD models. Recently, it has been
      found that agricultural chemicals, such as rotenone and paraquat, when
      administered systemically, can reproduce specific features of PD in rodents,
      apparently via oxidative damage. Transgenic animals that over-express alpha
      synuclein are used to study the role of this protein in dopaminergic
      degeneration. This review critically discusses animal models of PD and compares
      them with characteristics of the human disease.

PMID- 11948618
TI  - Digging for innate immunity since Darwin and Metchnikoff.
AB  - Immune systems are, increasingly, being studied from comparative perspectives.
      The analysis of the immune-defense systems of invertebrates, such as fruit flies
      and earthworms, is an important part of this effort. These systems are innate,
      natural non-specific, non-anticipatory and non-clonal. This is in contrast to the
      macrophage T and B systems that characterize vertebrate adaptive immunity whose
      properties can be categorized as adaptive, induced, specific, anticipatory, and
      clonal. In this review, we will focus on the earthworm system. Earthworms, like
      other complex invertebrates, possess several leukocyte types and synthesize and
      secrete a variety of immunoprotective molecules. The system as a whole effects
      phagocytosis, encapsulation, agglutination, opsonization, clotting and lysis of
      foreign components. At least two major leukocytes, small coelomocytes, and large
      coelomocytes mediate lytic reactions against several targets. Destruction of
      tumor cells in vitro shows that phagocytosis and natural killer cell responses
      are distinct properties of coelomocytes. A third type, the chlorogogen cell,
      synthesizes and sheds effector lytic molecules. Among the lytic molecules, three
      have been identified and sequenced (fetidins, CCF-1, lysenin) and another has
      been discovered (eiseniapore), while three other molecules, H(1) H(2) H(3), share
      agglutinating and lysing functions. In contrast to these, Lumbricin I is the only
      known molecule of the earthworm system that is antimicrobial but non-lytic.
      Altogether the cellular and humoral components of the earthworm system function
      to distinguish between self and not self, dispose of internal (cancer?), damaged
      components and external antigens (microbes). The evolutionary context of the
      earthworm innate immune system is discussed at the end of this article.

PMID- 11948619
TI  - How do features of sensory representations develop?
AB  - Sensory representations in the brainstem and cortex have a number of features
      that support the idea that neural activity patterns are important in their
      development. Many of these features vary across species in ways that could result
      from perturbances in the balance of the effects of activity patterns and position
      dependent gene expression. (1) Most notably, disruptions or septa in sensory maps
      often reflect actual discontinuities in the receptor sheet, and the
      discontinuities may be reflected in a series of interconnected maps. Species with
      different disruption patterns in sensory sheets have different matching
      disruption patterns in the sensory maps and variant individuals and strains of
      the same species have matching variations in the receptor disruption patterns and
      their sensory maps. (2) In addition, mutations that misdirect some of the retinal
      afferents from one side of the brain to the other create new sensory maps that
      preserve continuities in the altered pattern of input, while creating new
      structural discontinuities. (3) Furthermore, functionally different classes of
      afferents that are mixed in the receptor sheet often segregate to activate
      separate populations of target cells. (4) Finally, early developing portions of
      receptor sheets may gain more than their share of territory in sensory maps.
      These and other variable features of sensory maps are most readily accommodated
      by theories that involve roles for instruction by evoked and spontaneous neural
      activity patterns.

PMID- 11948620
TI  - Braking the silence: how heterochromatic gene repression is stopped in its
      tracks.
AB  - Eukaryotic DNA is assembled into nucleosomes, which are further packaged into
      higher order chromatin structures containing many non-histone chromosomal
      proteins. The details of this packaging have profound effects on gene expression
      and other cellular processes involving the genetic material. Heterochromatic
      domains of the genome are usually transcriptionally repressed, while euchromatic
      regions are transcriptionally competent. Current models of gene activation
      postulate the existence of boundary elements that either prevent inappropriate
      activation of genes by distal enhancers (enhancer blockers), or sequences that
      block the propagation of heterochromatin into euchromatic regions (barriers).
      While numerous boundary sequences have been identified, little is known with
      regard to the molecular mechanisms used to punctuate the genome. This review will
      focus on recent data that provide insight into the mode of action of barrier
      elements.

PMID- 11948621
TI  - Fascins, and their roles in cell structure and function.
AB  - The fascins are a structurally unique and evolutionarily conserved group of actin
      cross-linking proteins. Fascins function in the organisation of two major forms
      of actin-based structures: dynamic, cortical cell protrusions and cytoplasmic
      microfilament bundles. The cortical structures, which include filopodia, spikes,
      lamellipodial ribs, oocyte microvilli and the dendrites of dendritic cells, have
      roles in cell-matrix adhesion, cell interactions and cell migration, whereas the
      cytoplasmic actin bundles appear to participate in cell architecture. We discuss
      the current understanding of the cellular mechanisms that regulate the binding of
      fascin to actin and how these processes contribute to the organisation or
      disassembly of cell protrusions. Although the in vivo roles of fascin have been
      studied principally in Drosophila, several human diseases are associated with
      inherited or acquired alterations in the expression of fascins. Strategies to
      modulate fascin-containing protrusions and thereby cell adhesive and migratory
      behaviour could have potential for therapeutic intervention in these conditions.
      The supplementary material referred to in this section can be found at
      http://www.interscience.wiley.com/jpages/0265-9247/suppmat/2002/v24.350.html

PMID- 11948622
TI  - When Ets transcription factors meet their partners.
AB  - Ets proteins are a family of transcription factors that regulate the expression
      of a myriad of genes in a variety of tissues and cell types. This functional
      versatility emerges from their interactions with other structurally unrelated
      transcription factors. Indeed, combinatorial control is a characteristic property
      of Ets family members, involving interactions between Ets and other key
      transcriptional factors such as AP1, SRF, and Pax family members. Intriguingly,
      recent molecular modeling and crystallographic data suggest that not only the ETS
      DNA-binding domain, but also the DNA recognition helix alpha3, are often directly
      required for Ets partner's selection. Indeed, while most DNA-binding proteins
      appear to exploit differences within their DNA recognition helices for sites
      selection, the Ets proteins exploit differences in their surfaces that interact
      with other transcription factors, which in turn may modify their DNA-binding
      properties in a promoter-specific fashion. Taken together, the gene-specific
      architecture of these unique complexes can mediate the selective control of
      transcriptional activity.

PMID- 11948623
TI  - Regulator-driven functional diversification of protein phosphatase-1 in
      eukaryotic evolution.
AB  - We have used the (nearly) completed eukaryotic genome sequences to trace the
      evolution of thirteen families of established vertebrate regulators of type-1
      protein phosphatases (PP1). Two of these families are present in all lineages of
      the eukaryotic crown and therefore qualify as candidate primordial regulators
      that determined the surface of PP1. The set of regulators of PP1 has continued to
      expand ever since, often in response to functional innovations in different
      eukaryotic lineages. In particular, the development of metazoan multicellularity
      was accompanied by an explosive increase in the number of regulators of PP1. The
      further increase in the functional diversity of PP1 in the vertebrate lineage was
      mainly achieved by the duplication of genes for regulatory subunits and by the
      conversion of already existing proteins into regulators of PP1. Unexpectedly, our
      analysis has also enabled us to classify nine poorly characterized proteins as
      likely regulators of PP1.

PMID- 11948624
TI  - Novel adipocyte lines from brown fat: a model system for the study of
      differentiation, energy metabolism, and insulin action.
AB  - Adipose tissue has emerged as an important endocrine regulator of glucose
      metabolism and energy homeostasis. By virtue of the mitochondrial protein
      uncoupling protein-1 (UCP-1), brown fat additionally plays a unique role in
      thermoregulation. Interest has focused on this tissue not only as a target for
      pharmacotherapy of obesity and insulin resistance but also as an endocrine tissue
      with leptin secretion and high insulin sensitivity. Most studies of adipocytes
      have been limited either to primary cell culture or to a small number of
      established cell lines. Recently, we have generated immortalized brown adipocyte
      cell lines from single newborn mice of different knockout mouse models. These
      cell lines retain the main characteristics of primary cells including UCP-1
      expression. They display sensitive and diverse metabolic responses to insulin and
      adrenergic stimulation and have proven to be useful in the characterization of
      UCP regulation and the role of key insulin signaling elements for insulin action.
      Here, we outline common approaches to the generation of adipose tissue cell
      lines. Furthermore, we propose that the novel technique of generating brown
      adipocyte lines from a single newborn mouse will be instrumental in gaining
      further insight into the role of a broad range of signaling molecules in adipose
      tissue biology and in the pathogenesis of insulin resistance.

PMID- 11948625
TI  - Generating cell diversity in the nervous system.

PMID- 11948626
TI  - The genome in context: biologists and philosophers on epigenetics.

PMID- 11948627
TI  - Reproductive toxicology: the science today.
AB  - Reproductive toxicology is concerned with chemical or physical agents interfering
      with fertility in both gender. Adverse effects may be induced directly,
      especially in adult males by damaging the semen producing epithelium (e.g.,
      DBCP), or indirectly, predominantly by interfering with sex hormonal homeostasis.
      Many critical events must occur during well-defined periods of prenatal and early
      postnatal development of the reproductive system. Most of such differentiation
      processes, several of which in the male critically depend on inducing influences
      of androgens, cannot take place at later stages, and lack of "imprinting" will
      result in irreversible defects or dysfunctions. These processes might be
      disturbed by interfering agents (e.g., by anti-androgens: feminization), provided
      that the exposure is high enough. Several of the processes known to be essential
      for male development can also be altered in females by exposure to a large excess
      of androgens (masculinization). Essential processes required for normal male
      development include: 1) androgen-dependent differentiation of the male phenotype
      during late embryonic development, 2) differentiation of the male secondary sex
      organs during the fetal period, 3) formation of a fixed number of Sertoli cells
      during the perinatal period, 4) imprinting of male sexual behavior in defined
      brain areas during the perinatal period, 5) imprinting of the pulsatile GnRH
      regulation of hypophysial hormone formation in both gender via the hypothalamico
      hypophysial axis, and 6) differentiation of the male organism during puberty.
      Many effects on fertility can be induced on the adult organism. Besides a direct
      action on the receptors, inhibition of the feed back mechanism that guarantees
      sex hormonal homeostasis is another mode of action. Many synthetic steroid
      compounds exhibit effects on more than one receptor, thus causing a complex
      situation. This must also be taken into account when analyzing possible effects
      of "ecohormones." Adverse hormonal actions are well established from experience
      in clinical and experimental medicine, using either natural or synthetic sex
      hormones, or enzyme inhibitors. Possible effects of "environmental" agents either
      mimicking or inhibiting sex hormonal actions are less well studied in clinical
      trials. Because of considerable species differences in hormonal effects,
      especially in pharmacokinetics, data of animal studies are of limited predictive
      value for extrapolations in preventive hazard minimization (but may be useful for
      revealing possible mechanisms of action). Data of in-vitro studies are even less
      suitable for extrapolations. It may be doubted that exposure of the general
      population to "ecohormones" or "xenohormones" is sufficient to induce clear-cut
      clinical effects. Adverse effects induced by, e.g., greatly unbalanced diets or
      after accidental overdoses cannot be excluded.

PMID- 11948628
TI  - Preliminary evaluation of the cytotoxic and genotoxic potential of D-003: Mixture
      of very long chain fatty acids.
AB  - D-003 is a mixture of very long chain aliphatic acids purified from sugar cane
      wax, wherein octacosanoic acid represents the major component. Previous
      experimental studies have shown that D-003 inhibits platelet aggregation in
      rodents. Also, its lowers total (TC) and low-density lipoprotein cholesterol (LDL
      C) in normocholesterolemic rabbits in a dose-dependent manner and inhibits
      cholesterol biosynthesis in fibroblast cultures. The present study was performed
      to investigate the in vitro cytotoxic and genotoxic potential effects of D-003
      assessed through two tests: the neutral red (NR) assay and the Ames test.
      Positive and negative controls were included in each experimental series.
      Compared with controls, no cytotoxicity was evident after 24 and 72 h of
      treatment with doses up to 1,000 microg/ml in the NR assay. On the other hand, D
      003 (5-5,000 microg/plate) did not increase the frequency of reverse mutations in
      the Ames test in both alternatives with or without S9 mix metabolic activation
      and a pre-incubation step. The positive control chemicals included in each
      experiment, namely, treatment with sodium dodecyl sulphate (SDS) in the NR assay
      and sodium azide (NaAz), 2-aminofluorene (AF), and dimethylnitrosamine (DMNA) in
      the Ames test, induced the expected changes, such as a decrease in optical
      density (OD) values in the NR assay and an increase in the frequency of reverse
      mutations in the Ames test. The present results indicate that D-003 did not show
      evidence of cytotoxic or genotoxic potential in tests able to detect the ability
      of chemicals to disrupt cells (NR assay) or to induce gene mutations (Ames test).

PMID- 11948629
TI  - Protective action of propolis on the rat colon carcinogenesis.
AB  - Propolis is a honeybee product with several biological and therapeutical
      properties. Its effect on the process of colon carcinogenesis and DNA damage were
      evaluated in the male Wistar rats using the aberrant crypt foci (ACF) assay and
      the comet assay, respectively. For both tests, animals were treated with the
      colon carcinogen 1,2 dimethylhydrazine (DMH, 40 mg/kg, s.c.) for 2 weeks (two
      injections/week) in order to induce both DNA damage and ACF. The animals were
      divided into groups that received propolis (ethanolic extract) at three different
      doses (10, 30, and 90 mg/kg b.w., by gavage), either simultaneously or after DMH
      treatment. For the comet assay, peripheral blood samples were collected 4 h after
      the last DMH treatment. All animals were sacrificed at the 5th week for
      evaluation of ACF. The results show that only the intermediate dose (30 mg/kg) of
      propolis, administered after DMH initiation, is significantly associated to a
      smaller number of aberrant crypts in the distal colon. No effect on DNA damage in
      peripheral blood cells, however, was verified by the comet assay. These data
      suggest that propolis has a protective influence on the process of colon
      carcinogenesis, suppressing the development of preneoplastic lesions, and
      probably exerts no protection against the initiation of carcinogenesis.

PMID- 11948630
TI  - Low frequency noise and whole-body vibration cause increased levels of sister
      chromatid exchange in splenocytes of exposed mice.
AB  - Chronic exposure to low frequency (LF) noise and whole-body vibration (WBV)
      induces both physiological and psychological alterations in man. Recently, we
      have shown that long-term occupational exposure to LF noise and WBV produces
      genotoxic effects in man expressed as an increase in sister chromatid exchange
      (SCE) levels in lymphocytes. The objectives of the present study were to
      investigate whether the observed effect could be reproduced in a murine model
      and, if so, which of the agents, LF noise alone or in combination with WBV, would
      be instrumental in the SCE induction. SCEs were analyzed in spleen lymphocytes of
      mice exposed to LF noise alone and in combination with WBV for 300 and 600 hr. An
      effect at the cell cycle kinetics level was also investigated. The results
      revealed significant increases in the mean SCE number per cell and in the
      proportion of cells with high frequency of SCEs (HFCs) in lymphocytes of mice
      submitted to combined noise and WBV over controls. No significant differences
      were found between single noise-exposed and control mice. A cell cycle delay was
      observed exclusively in the noise and WBV exposure groups. In conclusion, we
      demonstrated that, as in exposed workers, prolonged exposure to the combination
      of LF noise and WBV determines an increase in SCE level in mice while LF noise
      alone is not effective in SCE induction.

PMID- 11948632
TI  - Evaluation of relationship between chromosome 22 and p53 gene alterations and the
      subtype of meningiomas by the interphase-FISH technique.
AB  - In this study, we investigated the relationship between genetic alterations such
      as chromosome 22 aneuploidy and p53 gene deletion, and the pathological types of
      meningioma of typical and aggressive forms. Thirty-four meningiomas (23 typical
      and 11 aggressive) were examined by application of fluorescence in situ
      hybridization (FISH) with chromosome 22 specific alpha satellite probe and a
      combination of p53 locus specific and chromosome 17 centromere specific alpha
      satellite probes, to evaluate the chromosome 22 aneuploidy and gain or loss of
      p53 gene along with chromosome 17. The results showed that, although chromosome
      22 aneuploidy was seen in 7 out of 23 typical (30.4%) and 4 out of 11 aggressive
      meningiomas (36.3%), no p53 deletion was detected in typical meningiomas, and p53
      deletion was detected in 3 out of 11 aggressive meningiomas (1 atypical and 2
      malignant), which had recurrence. There were no simultaneous occurrences of p53
      gene deletions between typical and aggressive meningiomas. The present findings
      indicate that the loss of chromosome 22 may be involved with tumorogenesis of
      typical and aggressive meningiomas, while p53 gene deletions may be involved with
      malignant progression and recurrence in the aggressive meningiomas.

PMID- 11948631
TI  - Investigation of genetic susceptibility to non-small cell lung cancer by fragile
      site expression.
AB  - Fragile sites are non-staining gaps and breaks in specific points of chromosomes
      that are inducible by various culture conditions. Previous studies have shown
      that various clastogenic agents increase expression of fragile sites. In this
      study, the expression of common fragile sites induced by aphidicolin was
      evaluated on prometaphase chromosomes obtained from peripheral blood lymphocytes.
      Chromosomal aberrations and fragile site expression of 60 individuals, including
      20 patients with non-small cell lung cancer (NSCLC), 20 of their clinically
      healthy family members, and 20 age-matched normal healthy controls without
      history of any cancer type were studied. Both the proportion of damaged cells (P
      < 0.001) and the mean number of gaps and breaks per cell (P < 0.001) were
      significantly higher in both the patients and relatives' groups when compared
      with the control group. However, they were insignificant when the patients were
      compared to their relatives (P > 0.05). We determined four aphidicolin type
      common fragile sites in our study. These sites in patients with NSCLC and
      relatives were the following: 1p21, 2q33, 3p14, and 16q23. In these fragile
      sites, 2q33, 3p14, and 16q23 sites were statistically significant when compared
      with control group (P < 0.001, P < 0.0005, and P < 0.05, respectively).
      Consequently, we believe that fragile site studies may be helpful to detection of
      cancer risk.

PMID- 11948633
TI  - In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage
      in sperm.
AB  - Isoflavones are plant compounds, proposed to have health benefits in a variety of
      human diseases, including coronary heart disease and endocrine-responsive
      cancers. Their physiological effects include possible antioxidant activity,
      therefore suggesting a role for isoflavones in the prevention of male
      infertility. The aim of this study was to test the antioxidant effects of the
      isoflavones genistein and equol on sperm DNA integrity, assessed in vitro after
      hydrogen peroxide-mediated damage, using the comet assay. Pre-treatment with
      genistein or equol at doses of 0.01-100 micromol/l significantly protected sperm
      DNA against oxidative damage. Both ascorbic acid (10-600 micromol/l) and alpha
      tocopherol (1-100 micromol/l) also protected. Compared with ascorbic acid and
      alpha-tocopherol, added at physiological concentrations, genistein was the most
      potent antioxidant, followed by equol, ascorbic acid, and alpha-tocopherol.
      Genistein and equol added in combination were more protective than when added
      singly. Based on these preliminary data, which are similar to those observed
      previously in lymphocytes, these compounds may have a role to play in antioxidant
      protection against male infertility.

PMID- 11948634
TI  - Re: Diabetes teratogenicity in mice is accompanied with distorted expression of
      TGF-beta2 in the uterus.

PMID- 11948636
TI  - Group size and structure in western lowland gorillas (Gorilla gorilla gorilla) at
      Mbeli Bai, Republic of Congo.
AB  - This paper describes the size and structure of western lowland gorilla groups
      visiting Mbeli Bai, a swampy forest clearing in northern Congo. An observation
      platform at the edge of the clearing was used over a 3-yr period, with gorillas
      visible for 1,681 hr. Data are presented on 14 groups and seven solitary males.
      Mean group size (excluding solitary males) was 8.4 +/- SD 4.3, and did not differ
      significantly from most other gorilla studies. All groups at Mbeli contained only
      one fully mature male and did not show evidence of fission-fusion or regular
      subgrouping. All emigrating males that remained in the population became
      solitary, and "bachelor" groups were not observed. Methodological issues are
      raised, including the classification of multi-male groups, and the demographic
      profiles of other populations are discussed in the light of results from Mbeli.

PMID- 11948637
TI  - Genetics and caging type affect birth weight in captive pigtailed macaques
      (Macaca nemestrina).
AB  - The heritability of birth weight was estimated in 3,562 captive pigtailed
      macaques using 30 years of breeding and pedigree records. Based on a pedigree of
      over 12,000 animals, quantitative genetic analyses were performed using
      statistical variance decomposition methods. The model included additive genetic
      effects, cytoplasmic genetic effects, birth environment, shared maternal
      environment, and unmeasured environmental effects. The results demonstrated a
      strong (h(2) = 0.51) heritable component of birth weight overall, and included
      significant additive genetic heritability (h(2) = 0.23), and cytoplasmic
      heritability (h(2) = 0.09). In addition, a significant effect of birth location
      and cage type was identified, explaining an additional 6% of birth weight
      variance. The use of a nonhuman primate model for studying the effects of genes
      on birth weight eliminated many of the problems associated with confounding
      variables in human studies, and allowed for the quantification of a heritable
      component of birth weight.

PMID- 11948638
TI  - Counter aggression and reconciliation in Assamese macaques (Macaca assamensis).
AB  - Patterns of aggressive and affiliative behavior, such as counter aggression and
      reconciliation, are said to covary in the genus Macaca; this is referred to as
      the systematic variation hypothesis. These behavior patterns constitute a species
      dominance style. Van Schaik's [1989] socioecological model explains dominance
      style in macaques in terms of within- and between-group contest competition.
      Dominance style is also said to correlate with phylogeny in macaques. The present
      study was undertaken to examine phylogenetic and socioecological explanations of
      dominance style, as well as the systematic variation hypothesis. We collected
      data on counter aggression and reconciliation from a habituated group of Assamese
      macaques (Macaca assamensis) at the Tukeswari Temple in Assam, India. The
      proportion of agonistic episodes that involved counter aggression was relatively
      low. Counter aggression, however, occurred more often among males than among
      females, and it was most common when females initiated aggression against males.
      The conciliatory tendency for this group of Assamese macaques was 11.2%. The
      frequency of reconciliation was low for fights among males and for fights among
      females, but reconciliation was particularly rare for opposite-sexed opponents.
      Female social relationships were consistent with the systematic variation
      hypothesis, and suggest a despotic dominance style. A despotic dominance style in
      Assamese macaques weakens the correlation between dominance style and phylogeny
      in macaques, but it is not inconsistent with the socioecological model. Male
      female relationships were not well explained by the despotic-egalitarian
      framework, and males may well have more tolerant social relationships than do
      females. Sex differences need to be considered when categorizing species
      according to dominance style.

PMID- 11948639
TI  - Patterns of lateralized hand use in an arboreal primate, Simias concolor.
AB  - Studies of hand use in nonhuman primates suggest that several species exhibit
      hand preferences for a variety of tasks. The majority of studies, however, focus
      on the lateralized hand use of captive nonhuman primate populations. Although
      captive settings offer a more controlled environment for assessing hand
      preferences, studies of wild populations provide important insights into how
      handedness is affected by natural environmental conditions and thus potential
      insights into the evolution of handedness. To investigate handedness in a
      population of wild nonhuman primates, we studied patterns of lateralized hand use
      during feeding in four simakobu monkeys (Simias concolor), an arboreal species
      inhabiting the Mentawai Islands, Indonesia. Our data show that individual
      variation in hand preferences for feeding existed among our study animals. In
      addition, each simakobu expressed a significant hand preference for supporting
      itself on a branch during feeding, an uncoordinated bimanual task. This bias was
      most prevalent when the branch used for support was a main branch rather than a
      terminal branch. When both hands were employed in a coordinated bimanual feeding
      activity (bimanual manipulation), only two subjects showed a significant bias for
      feeding. Our data suggest that these individuals are more likely to express
      significant hand preferences when feeding from stable, rather than precarious,
      positions within the canopy.

PMID- 11948640
TI  - Effectiveness of human microsatellite loci for assessing paternity in a captive
      colony of vervets (Chlorocebus aethiops sabaeus).
AB  - Microsatellite polymorphisms are playing an increasingly vital role in
      primatological research, and are particularly useful for paternity exclusion in
      both wild and captive populations. Although vervet monkeys (Chlorocebus aethiops)
      are commonly studied in both settings, few previous studies have utilized
      microsatellite markers for assessing genetic variation in this species. In a
      pilot project to assess paternity in the UCLA-VA Vervet Monkey Research Colony
      (VMRC), we screened 55 commercially available human microsatellite markers chosen
      from a panel of 370 that have been shown to be polymorphic in baboons (Papio
      hamadryas). Using a standard PCR protocol, 43 (78%) loci produced amplifiable
      product. Of these, 14 were polymorphic and 11 were genotyped in 51 individuals,
      including 19 offspring and 14 potential sires. The average heterozygosity across
      the 11 loci was.719. In all 19 paternity cases all but one male was excluded as
      the true sire at two or more loci. This includes successfully distinguishing
      between two maternal half-sib brothers who were potential sires in most of the
      paternity cases. Given that the colony is descended from 54 wild-caught founders
      trapped between 1975 and 1987 from an introduced population on St. Kitts, West
      Indies, these values imply high microsatellite variability in natural vervet
      populations. Our results provide a panel of markers derived from the human genome
      that is suitable for assessing genetic variation and paternity in vervets.

PMID- 11948641
TI  - Research on energy expenditure in individuals with eating disorders: a review.
AB  - OBJECTIVE: This study reviews the published research on energy expenditure in
      individuals with anorexia nervosa (AN), bulimia nervosa (BN), and binge eating
      disorder (BED). METHOD: Individual studies are reviewed and their results
      summarized. RESULTS: The most consistent finding is evidence of reduction in
      resting energy expenditure (REE) in patients with AN, which increases with
      increased energy intake and body weight. Data regarding BN are inconsistent.
      Three available studies in subjects with BED have not found evidence of changes
      in energy expenditure corrected for lean body mass compared with obese non-binge
      eaters. DISCUSSION: The ability to reliably and cost-effectively measure REE may
      aid in the refeeding of patients with AN where REE is reduced. Changes in BN and
      BED subjects have yet to be identified consistently.

PMID- 11948642
TI  - Excessive exercise in anorexia nervosa and bulimia nervosa: relation to eating
      characteristics and general psychopathology.
AB  - OBJECTIVE: Excessive exercise is a well-known phenomenon in anorexia nervosa, but
      less is known about its role in bulimia nervosa. In addition, there is little
      evidence regarding the psychopathological processes that might act as
      predisposing, triggering, or maintaining factors for such exercise. The present
      study examined the presence of excessive exercise in different women with eating
      disorders, and its psychopathological correlates. METHODS: Case notes from 63
      anorexia nervosa and 61 bulimia nervosa patients were examined. Two-way
      multivariate analyses of variance (diagnosis x use of excessive exercise) were
      used to determine the impact of the two factors upon eating characteristics (EAT
      40 and BITE) and psychopathological symptoms (SCL-90-R). RESULTS: While high
      levels of depression were more likely among all patients who used excessive
      exercise, levels of anxiety and somatization were particularly high only among
      those anorexics who exercised excessively. DISCUSSION: Possible explanatory
      models are advanced to account for this pattern of findings, focusing on the
      possible use of exercise as an affect regulation strategy among anorexia nervosa
      patients. Further research is suggested to test and develop this model, and
      possible clinical implications are outlined.

PMID- 11948643
TI  - Pseudoparadoxical impulsivity in restrictive anorexia nervosa: a consequence of
      the logic of scarcity.
AB  - OBJECTIVE: To explain an apparently paradoxical pattern wherein sufferers of
      restrictive anorexia nervosa exhibit both rigorous self-restraint and episodic
      impulsivity. METHOD: The experimental, historical, and clinical literatures were
      examined for evidence of psychological and behavioral changes accompanying severe
      dietary constriction; such changes were noted and compared with those reported to
      occur in anorexics. RESULTS: Increased impulsivity in association with dietary
      constriction is described in diverse literatures. A number of lines of evidence
      suggest that the serotonergic system mediates this change. DISCUSSION: Many forms
      of impulsivity can be understood as having once constituted fitness-enhancing
      responses to resource scarcity. It is suggested that an evolved psychological
      mechanism calibrates the individual's sensitivity to risk in light of future
      prospects. Self-injurious behaviors are explicable as misfirings of such a
      mechanism. Similarly, excessive exercising by anorexics may reflect the
      misdirection of reward systems that normally encourage adaptive increases in
      ranging behavior under conditions of scarcity.

PMID- 11948645
TI  - Girls' recurrent and concurrent body dissatisfaction: correlates and consequences
      over 8 years.
AB  - OBJECTIVE: The present study examines the patterns of body dissatisfaction during
      adolescence in order to determine whether girls enter onto trajectories of body
      dissatisfaction that are associated with eating and depressive symptoms during
      adolescence and in young adulthood. METHOD: Body dissatisfaction was studied in
      120 adolescent girls drawn from a normal population of students enrolled in
      private schools in a major metropolitan area. They were seen at three times over
      an 8-year period (mean ages = 14.3, 16.0, and 22.3). RESULTS: Recurrent body
      dissatisfaction during adolescence was associated with earlier pubertal
      maturation and elevated depressive and eating symptoms in young adulthood
      compared with girls who maintained positive body images during adolescence.
      Concurrent body dissatisfaction was also a correlate of greater depressed affect
      and eating symptoms at the time these girls experienced body dissatisfaction.
      DISCUSSION: Findings suggest that adolescent body dissatisfaction has
      consequences for affect in adulthood.

PMID- 11948644
TI  - Disordered eating and substance use in an epidemiological sample: I. Associations
      within individuals.
AB  - OBJECTIVE: This study examined the strength of associations between disordered
      eating and eating disorders and substance use and substance use disorders
      (SU/SUDs) in an epidemiological sample. METHODS: 672 adolescent girls and 718
      women completed structured interviews of lifetime eating disorders and substance
      use and misuse, as well as self-reported current disordered eating attitudes and
      behaviors. RESULTS: Although effect sizes were small, eating attitudes and
      disorders were associated modestly with nicotine, alcohol, and drug use, and with
      nicotine dependence in adolescent girls. Alcohol use and misuse were related to
      eating attitudes and pathology in women. SU/SUDs were associated with restricting
      and bulimic behaviors and no prominent differences in associations were observed
      between substance classes. In contrast to findings in clinical populations, these
      community-based results were positive but generally weak, suggesting there is no
      strong, overarching relationship between eating and substance use problems.
      DISCUSSION: These results have implications for the addiction model of eating
      disorders.

PMID- 11948646
TI  - Body image disturbance in obese outpatients before and after weight loss in
      relation to race, gender, binge eating, and age of onset of obesity.
AB  - OBJECTIVE: To assess body image disturbance as a composite of three aspects
      (distortion, discrepancy, and dissatisfaction) in obese subjects before and after
      weight loss. Disturbance was then related to race, gender, binge eating behavior,
      and age of onset of obesity. METHODS: Eighty-two obese outpatients (24 males, 58
      females) completed the Stunkard Figure Rating Scale (FRS). A Disturbance score
      was derived from the weighted sum of distortion, discrepancy, and
      dissatisfaction. The measures were repeated 4 weeks after starting a medically
      supervised liquid formula diet. RESULTS: Prior to weight loss, race (r =.28, p
      =.01) and gender (r =.25, p =.02) were each predictive of disturbance, with
      Caucasians and men having the most disturbance. Binge eaters exhibited more
      discrepancy (p =.03) and dissatisfaction (p =.005) than non-binge eaters. Early
      onset subjects demonstrated more discrepancy than adult-onset subjects (p =.02).
      Following weight loss, disturbance scores decreased for all groups (p =.009).
      However, early-onset subjects still showed more discrepancy (p =.002) and more
      dissatisfaction (p =.005) than adult-onset subjects. DISCUSSION: Body image
      disturbance was viewed as a composite of three aspects. Prior to weight loss, the
      high disturbance score in Caucasians may be due to them experiencing greater
      cultural pressure to be thin. The men may have exaggerated their degree of
      obesity because of less denial of being overweight than women. Following weight
      loss, disturbance decreased for all groups but remained elevated for those with
      early onset, possibly because of a persistent self-image from adolescence.

PMID- 11948647
TI  - Global and dimensional self-esteem in preadolescent and early adolescent children
      who are overweight: age and gender differences.
AB  - OBJECTIVE: To examine age and gender differences in global and dimensional self
      esteem in children who are overweight. METHOD: As part of a pretreatment
      assessment, the Perceived Competence Scale for Children was completed by 121
      children (ages 8-14) who were overweight and enrolling in a weight reduction
      program. RESULTS: Gender differences in general self-esteem and age differences
      in physical self-esteem were found. Also, girls who were highly overweight
      reported lower physical self-esteem than girls who were moderately overweight.
      However, for boys, the opposite pattern emerged. For both boys and girls,
      cognitive and social self-esteem predicted general self-esteem and physical self
      esteem did not. DISCUSSION: Children who are overweight may emphasize dimensions
      of their self-esteem in nongender stereotyped ways that are protective of their
      general self-esteem. Understanding developmental trends and gender differences in
      self-esteem can enhance our ability to assist youth who are overweight in
      maintaining favorable self-evaluations.

PMID- 11948650
TI  - The impact of body image experiences: development of the body image quality of
      life inventory.
AB  - OBJECTIVE: Substantial research confirms that body image affects multiple aspects
      of psychosocial functioning, yet there is no direct assessment to quantify its
      impact on an individual's quality of life. METHOD: In the present study, the Body
      Image Quality of Life Inventory was developed and empirically evaluated with 116
      college women. RESULTS AND DISCUSSION: This 19-item assessment was internally
      consistent and stable over a 2- to 3 week period. It converged significantly with
      multiple measures of body image evaluation and investment and with body mass. The
      results further revealed that women in the sample reported more positive than
      negative consequences of their body image for various domains of life. The
      implications of these findings and directions for continued validation of this
      unique measure are considered.

PMID- 11948649
TI  - The role of acculturative stress and body dissatisfaction in predicting bulimic
      symptomatology across ethnic groups.
AB  - OBJECTIVE: This study examines the interactive effects of acculturative stress
      and body dissatisfaction in prediction of bulimic symptoms, particularly in non
      White females. METHOD: We administered questionnaires to White, Black, and
      Hispanic females on acculturative stress, body dissatisfaction, and bulimic
      symptoms. RESULTS: Our results show that among minority women who report low
      levels of acculturative stress, body dissatisfaction and bulimia were not
      correlated. However, among minority women who reported high levels of
      acculturative stress, body dissatisfaction and bulimia were highly and
      significantly correlated. DISCUSSION: The combination of acculturative stress and
      body dissatisfaction may render minority women more vulnerable to bulimic
      symptoms; the absence of acculturative stress among minority women may buffer
      them against bulimic symptoms, even in the presence of body dissatisfaction.

PMID- 11948648
TI  - Loss of control over eating, adiposity, and psychopathology in overweight
      children.
AB  - OBJECTIVE: To investigate the relationship between loss of control over eating,
      adiposity, and psychological distress in a nontreatment sample of overweight
      children. METHOD: Based on self-reports of eating episodes, 112 overweight
      children, 6-10 years old, were categorized using the Questionnaire of Eating and
      Weight Patterns-Adolescent Version into those describing episodes of loss of
      control over eating (LC), and those with no loss of control (NoLC). Groups were
      compared on measures of adiposity, dieting, and eating behavior, and associated
      psychological distress. RESULTS: LC children (33.1%) were heavier and had greater
      amounts of body fat than NoLC children. They also had higher anxiety, more
      depressive symptoms, and more body dissatisfaction. 5.3% met questionnaire
      criteria for BED. Episodes of loss of control occurred infrequently, were often
      contextual, and involved usual meal foods. DISCUSSION: As in adults, overweight
      children reporting loss of control over eating have greater severity of obesity
      and more psychological distress than those with no such symptoms. It remains
      unknown whether children who endorse loss of control over eating before
      adolescence will be those who develop the greatest difficulties with binge eating
      or obesity in adulthood.

PMID- 11948652
TI  - Anorexia nervosa following sexual harassment on the internet: a case report.
AB  - BACKGROUND: Sexual abuse may be a risk factor for the development of anorexia
      nervosa. No information is available on sexual abuse through the Internet and its
      connection to the development of eating disorders. METHOD: We report on a case of
      an adolescent female with the diagnosis of anorexia nervosa, whose symptomatology
      correlated significantly with an incident of sexual harassment experienced via
      the Internet. RESULTS: A case of on-line harassment suffered without off-line
      follow-up is reported to have led to a restrictive type of anorexia nervosa,
      where the symptomatology was connected to a "computer scatology" like persecution
      of our patient. DISCUSSION: A causal connection of the on-line sexual harassment
      suffered and development of eating disorder is reported.

PMID- 11948651
TI  - Validation of eating and dieting expectancy measures in two adolescent samples.
AB  - OBJECTIVE: To demonstrate the validity of two measures of eating and dieting
      expectancies (The Eating Expectancy Inventory [EEI] and the Thinness and
      Restricting Expectancy Inventory, [TREI]) for use with adolescents. METHOD:
      Seventh (N = 392) and tenth graders (N = 300) completed the Bulimia Test-Revised
      (BULIT-R), the Eating Disorder Inventory (EDI-II), and two factors of the Three
      Factor Eating Questionnaire (TFEQ). RESULTS: Findings replicated for the two
      adolescent samples. The expectancy that thinness leads to overgeneralized life
      improvement correlated with measures of "successful" dieting, dieting plus
      disinhibition, and bulimic symptomatology. Expectancies for negative
      reinforcement from eating (e.g., eating helps manage negative affect and
      alleviate boredom) correlated with dieting plus disinhibition and bulimic
      symptoms, but not with successful dieting. Negative reinforcement from eating and
      reinforcement from thinness expectancies accounted for different bulimic symptom
      variance than that accounted for by the personality factors of perfectionism,
      interpersonal distrust, and ineffectiveness. DISCUSSION: Results were consistent
      with prior work on college and clinical samples, thus supporting use of the
      expectancy measures with adolescents.

PMID- 11948653
TI  - Anorexia nervosa with comorbid psychosis and borderline mental retardation: a
      case report.
AB  - Anorexia nervosa (AN) is often associated with comorbid depression or anxiety,
      but rarely with mental retardation or psychosis. METHODS: The present report
      describes the case of a 22 year-old woman who met diagnostic criteria for
      anorexia nervosa, borderline mental retardation, and schizoaffective disorder.
      RESULTS AND DISCUSSION: The case highlights the difficulties in differential
      diagnosis with these seemingly incompatible disorders. It also provides some
      insights into the unclear relationship between anorexia nervosa and these
      comorbid conditions.

PMID- 11948654
TI  - Molecular recognition and supramolecular chemistry in the gas phase.
AB  - Supramolecular chemistry, in particular, the fields of molecular recognition and
      self-assembly, profit much from the development of soft ionization techniques and
      advanced methods for mass analysis and gas-phase chemistry. Vice versa, weakly
      bonded architectures and host-guest complexes represent a veritable challenge for
      the mass spectrometrist, leading to further development of methods and
      techniques. This review describes the state-of-the-art in this field, and
      includes topics such as the effects of solvation on meta binding to crown ethers,
      chiral discrimination of guests by chiral hosts, the elucidation of the secondary
      structure of self assembled complexes, and the mechanistic pathways of self
      assembly or the fragmentations of supramolecular complexes in the gas phase.

PMID- 11948655
TI  - Analysis of nucleic acids by on-line liquid chromatography-mass spectrometry.
AB  - The numerous problems posed by modern biochemistry, biology, and medicine, as
      well as the growing significance of genetic engineering require the application
      of fast and reliable methods of utmost sensitivity and selectivity for the
      analysis of nucleic acids. High-performance liquid chromatography (HPLC) and mass
      spectrometry (MS) represent established analytical techniques for the
      characterization and structural elucidation of single- and double-stranded
      nucleic acids, ranging in size from a few nucleotides to several thousand base
      pairs. Although both techniques are independently applicable for nucleic acid
      analysis, the on-line hyphenation significantly enhances their potential for the
      robust and fully automable routine analysis of minute amounts of biological
      samples. Among the various chromatographic and mass spectrometric modes available
      in principle, ion-pair reversed-phase HPLC and electrospray ionization mass
      spectrometry (ESI-MS) have been shown to be the most suitable for the direct
      interfacing of liquid chromatography (LC) and MS. Instrumental setup, as well as
      chromatographic and mass spectrometric experimental conditions, need to be
      carefully selected in order to maximize the performance of the hyphenated
      analytical system. Applications of HPLC-ESI-MS include the characterization of
      oligodeoxynucleotides synthesized by solid-phase synthesis, the analysis of
      antisense oligodeoxynucleotides, oligonucleotide metabolites, and DNA adducts,
      the analysis of genomic segments specifically amplified by the polymerase chain
      reaction (PCR), the characterization of ribonucleic acids, the sizing of double
      stranded DNA restriction fragments, the genotyping of short tandem repeats (STRs)
      and single nucleotide polymorphisms (SNPs), the detection of mutations in nucleic
      acid sequences, and the sequencing of nucleic acids.

PMID- 11948656
TI  - Selected reviews on mass spectrometric topics--XCIV.

PMID- 11948657
TI  - Role of HuD and other RNA-binding proteins in neural development and plasticity.
AB  - Transcription factors have traditionally been viewed as the main determinants of
      gene expression. Yet, in recent years it has become apparent that RNA-binding
      proteins also play a critical role in determining the levels of expression of a
      large number of genes. Once mRNAs are transcribed, RNA-binding proteins can
      control all subsequent steps in their function, from alternative splicing and
      translation to mRNA transport and stability. In the nervous system, a large
      number of genes are regulated post-transcriptionally via the interaction of their
      mRNAs with specific RNA-binding proteins. This type of regulation is particularly
      important in the control of the temporal and spatial pattern of gene expression
      during neural development. This review will discuss the function of the embryonic
      lethal abnormal vision (ELAV)/Hu family of nervous system-specific RNA-binding
      proteins, with a special emphasis on HuD, a member of this family that controls
      GAP-43 mRNA stability and expression. In addition, we will present recent
      findings on other neural RNA-binding proteins: the ribonucleoprotein K homology
      (KH)-domain proteins, Fragile X mental retardation protein (FMRP), quakinguiable
      protein (QKI), and Nova-1. Together with the ELAV/Hu family, these proteins are
      essential for proper neural development and in some cases for plasticity in the
      mature brain. The biological significance of these proteins is evident not only
      by their evolutionary conservation but also by the magnitude of problems arising
      from autoimmune reactions against them or from mutations affecting their
      expression or function.

PMID- 11948658
TI  - Finding new candidate genes for learning and memory.
AB  - The genetic mechanisms underlying learning and memory remain mysterious, but many
      of the genes are likely to be expressed in the hippocampus, a region pivotal to
      this process. We used a 9,000 gene microarray to examine differences in
      hippocampal gene expression between two F1 hybrid mouse strains that perform well
      on the Morris water maze and two inbred strains that perform poorly. This
      resulted in identification of 27 differentially expressed genes, which could be
      used to place the F1 hybrid and inbred strains into separate clusters based on
      singular value decomposition. Most of the genes have unknown function, but those
      with known functions may provide clues to the molecular mechanisms of learning.
      Using multiple strains to narrow down the number of candidate genes should be a
      useful general approach to genome-wide studies of behavioral and other complex
      traits.

PMID- 11948659
TI  - Bergmann glial cells form distinct morphological structures to interact with
      cerebellar neurons.
AB  - It is well established that Bergmann glial cells closely interact with neuronal
      elements in the molecular layer of the cerebellum. We reconstructed dye-labeled
      Bergmann glial cells from electron microscopic serial sections and identified
      their contact sites with neurons as "glial microdomains" (Grosche et al. [1999]
      Nature Neurosci. 2:139-143). In the present paper we describe these structures in
      more detail, and show that 1) immature Bergmann fibers up to postnatal day 7 are
      smooth and lack appendages but contain several large mitochondria at sites where
      the first indications of growing side branches are observed; 2) Bergmann fibers
      from cerebella at postnatal day 30 form two types of outgrowths, short simple
      thorns and longer complex appendages; 3) each of the latter (i.e., a glial
      microdomain) is in contact with only a few synapses and nonsynaptic neuronal
      excrescences; 4) every given region of the neuropil is occupied by (at least) two
      interdigitating glial microdomains; 5) the synaptic clefts are entirely
      surrounded by glial protrusions, whereas the extrasynaptic surfaces and small
      axons are only partially covered; and 6) many small neuronal excrescenses without
      vesicles are completely ensheathed by glial caps, representing novel glial
      neuronal structures of unknown function (glial thimbles). Computational modelling
      of the microdomains indicates that each is electrotonically independent of the
      stem process from which it arises, as well as of neighbouring domains. We assume
      that the glial microdomain is a morphological unit to compartmentalize ensembles
      of synapses, serving to synchronize local synaptic activity.

PMID- 11948660
TI  - Identification of Gas6, a putative ligand for Sky and Axl receptor tyrosine
      kinases, as a novel neurotrophic factor for hippocampal neurons.
AB  - Sky (also known as "Tyro3" and "Rse") is a member of the Axl/Sky/Mer receptor
      tyrosine kinase family and has two immunoglobulin-like repeats and two
      fibronectin type III-like repeats in the extracellular domain. Gas6 is a ligand
      for all members of the Axl family, each of which (Axl, Sky, and c-Mer) has
      different affinities to Gas6. Physiological functions of Sky and Gas6 in the
      nervous system are not well understood, despite their importance, which is
      suggested by Sky structural features and its predominant expression in the brain.
      We found in the RNase protection assays that gas6 and sky mRNAs are expressed in
      the adult rat hippocampus and are similarly regulated during development.
      Expression levels were low during embryonic stages but gradually increased during
      development and reached the highest level in adulthood. Sky, but not Axl,
      immunoreactivity was observed in the adult hippocampus. Recombinant rat Gas6
      attenuated hippocampal neuronal cell death that was caused by serum starvation in
      vitro, indicating that Gas6 is a novel neurotrophic factor for hippocampal
      neurons. Gas6 showed regulated expression in the sciatic nerve after nerve
      transection. Therefore, Sky and Gas6 have neurotrophic roles in the nervous
      system.

PMID- 11948661
TI  - Bone morphogenetic proteins BMP-6 and BMP-7 have differential effects on survival
      and neurite outgrowth of cerebellar granule cell neurons.
AB  - The bone morphogenetic proteins (BMPs) play an inductive role in the generation
      of cerebellar granule cells embryonically. Therefore, we chose to look at their
      effects on cerebellar granule cell survival and differentiation postnatally. The
      cells express mRNA for both BMP-6 and BMP-7, as well as for the receptors BMPRIA
      and BMPRII, demonstrating that the postnatal cells have the ability to form the
      heterodimer receptors needed to respond to BMPs. BMP-7 promotes cell survival,
      with a maximal effect at 10 ng/ml, whereas tenfold more BMP-6 is needed: Both
      were active over the course of 8 days in culture. In addition, both BMPs were
      able to protect the neurons against death from induced apoptosis (exposure to
      serum-free, low-potassium medium) or exposure to glutamate. However, only BMP-6
      could stimulate neurite outgrowth, measured with a neurofilament ELISA, an effect
      that was seen over the first 6 days in culture. These results, taken together
      with others in the literature, suggest that the BMPs have strong neurotrophic
      effects that are both neuron specific and BMP specific.

PMID- 11948662
TI  - Phosphatidylinositol kinase enzymes regulate the retrograde axonal transport of
      NT-3 and NT-4 in sympathetic and sensory neurons.
AB  - Phosphatidylinositol 3-kinase (PI3-kinase) and phosphatidylinositol 4-kinase (PI4
      kinase) enzymes are an important family of signaling molecules that have been
      implicated in the regulation of intracellular vesicle trafficking. It has
      previously been shown that PI3-kinase and PI4-kinase enzymes regulate neuronal
      survival and the retrograde axonal transport of nerve growth factor in
      sympathetic and sensory neurons. We have extended these studies to examine the
      role these enzymes play in the regulation of the retrograde axonal transport of
      neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) in sympathetic and sensory
      neurons in vivo. Wortmannin (0.1 nmol/eye), a PI3-kinase and PI4-kinase
      antagonist, reduced the amount of (125)I-NT-3 retrograde transport in sympathetic
      neurons by approximately 50% and (125)I-NT-4 in sympathetic neurons by
      approximately 40% and sensory neurons by approximately 20%. The PI3-kinase
      antagonist LY294002 (100 nmol/eye) reduced the retrograde axonal transport of
      (125)I-NT-4 in sympathetic and sensory neurons, and (125)I-NT-3 in sympathetic
      neurons. Phenylarsine oxide (PAO), a PI4-kinase antagonist, significantly
      inhibited (125)I-NT-4 retrograde axonal transport in sympathetic and sensory
      neurons. These results show that wortmannin-sensitive PI3-kinases and PI4-kinases
      may be involved in NT-3 and NT-4 retrograde axonal transport. The retrograde
      axonal transport of neurotrophic factors in sympathetic and sensory neurons in
      vivo appears to depend upon the activation of different receptors and second
      messenger cascades at the nerve terminal.

PMID- 11948663
TI  - Olfactory receptor expressed in ganglia of the autonomic nervous system.
AB  - Certain members of the olfactory receptor superfamily appear to be expressed not
      only in chemosensory neurons of the nasal epithelium. Analyzing the transgenic
      mouse line MOL2.3-IGITL, the olfactory receptor subtype MOL2.3 was found to be
      expressed in distinct subpopulations of cells within a cranial, a cervical as
      well as within a thoracic ganglion. By means of coexpressed markers, the axonal
      processes of MOL2.3 expressing cells could be visualized and thus the target
      tissues innervated by these ganglionic neurons identified. Stained fibers, but no
      stained cell bodies were visible in distinct head regions, notably in the lateral
      nasal gland and in the so-called Harderian gland; staining was also observed on
      distinct segments of blood vessels, especially within the tongue. In the thoracic
      region, the heart and a small segment of the aorta as well as a distinct
      population of lung alveoli were labeled by incoming blue fibers. Expression of
      MOL2.3 in cells of the autonomic nervous system supports the idea that at least
      some of the multiple olfactory receptor types serve functions others than odorant
      detection.

PMID- 11948664
TI  - Overexpression of neurofilament H disrupts normal cell structure and function.
AB  - Studying exogenously expressed tagged proteins in live cells has become a
      standard technique for evaluating protein distribution and function. Typically,
      expression levels of experimentally introduced proteins are not regulated, and
      high levels are often preferred to facilitate detection. However, overexpression
      of many proteins leads to mislocalization and pathologies. Therefore, for
      normative studies, moderate levels of expression may be more suitable. To
      understand better the dynamics of intermediate filament formation, transport, and
      stability in a healthy, living cell, we inserted neurofilament heavy chain (NFH)
      green fluorescent protein (GFP) fusion constructs in adenoviral vectors with
      tetracycline (tet)-regulated promoters. This system allows for turning on or off
      the synthesis of NFH-GFP at a selected time, for a defined period, in a dose
      dependent manner. We used this inducible system for live cell imaging of changes
      in filament structure and cell shape, motility, and transport associated with
      increasing NFH-GFP expression. Cells with low to intermediate levels of NFH-GFP
      were structurally and functionally similar to neighboring, nonexpressing cells.
      In contrast, overexpression led to pathological alterations in both filament
      organization and cell function.

PMID- 11948665
TI  - Suppression of BDNF-induced expression of neuropeptide Y (NPY) in cortical
      cultures by oxygen-glucose deprivation: a model system to study ischemic
      mechanisms in the perinatal brain.
AB  - The aim of this study was to establish a culture system that can serve as a model
      to study hypoxic-ischemic mechanisms regulating the functional expression of NPY
      neurons in the perinatal brain. Using an aggregate culture system derived from
      the rat fetal cortex, we defined the effects of oxygen and glucose deprivation on
      NPY expression, using BDNF-induced production of NPY as a functional criterion.
      NPY neurons exhibited a differential susceptibility to oxygen and glucose
      deprivation. Although the neurons could withstand oxygen deprivation for 16 hr,
      they were dramatically damaged by 8 hr of glucose deprivation and by 1-4 hr of
      deprivation of both oxygen and glucose (N+Glu-). One-hour exposure to N+Glu- led
      to a transient inhibition ( approximately 50%) of NPY production manifesting
      within 24 hr and recovering by 5 days thereafter, a 2-hr exposure to N+Glu- led
      to a sustained inhibition (50-75%) manifesting 1-5 days thereafter, and a 4-hr
      exposure to N+Glu- led to a total irreversible suppression of BDNF-induced
      production of NPY manifesting within 24 hr and lasting 8 days after re-supply of
      oxygen and glucose. Moreover, 1-hr exposure to N+Glu- led to a substantial and 4
      hr exposure led to a total disappearance of immunostaining for MAP-2 and NPY but
      not for GFAP; indicating that neurons are the primary cell-type damaged by oxygen
      glucose deprivation. Analysis of cell viability (LDH, MTT) indicated that
      progressive changes in cell integrity take place during the 4-hr exposure to
      N+Glu- followed by massive cell death 24 hr thereafter. Thus, we defined a
      culture system that can serve as a model to study mechanisms by which ischemic
      insult leads to suppression and eventually death of NPY neurons. Importantly,
      changes in NPY neurons can be integrated into the overall scheme of ischemic
      injury in the perinatal brain.

PMID- 11948666
TI  - Ethanol exposure enhances cell death in the developing cerebral cortex: role of
      brain-derived neurotrophic factor and its signaling pathways.
AB  - Exposure to ethanol during fetal development induces brain damage, causing cell
      loss in several brain areas and affecting synaptic connections. Because
      neurotrophin signaling plays an important role in neuronal survival and
      differentiation, we have investigated the effect of ethanol exposure on cell
      death in the developing cerebral cortex and whether this effect correlates with
      alterations in brain-derived neurotrophic factor (BDNF) levels, expression of its
      receptors, TrkB, and its signaling. We report that chronic ethanol intake during
      gestation and lactation enhances natural cell death and induces cell necrosis,
      decreases BDNF levels, and increases the ratio of the truncated to full-length
      TrkB mRNA receptors during postnatal developing cerebral cortex. Furthermore, we
      provide evidence that during brain development BDNF activates the extracellular
      signal-regulated kinases (ERK1 and ERK2) and the phosphoinoside-3-kinase (PI-3
      K/Akt) pathways. However, BDNF-induced cell signaling throughout the above
      mentioned survival pathways is significantly reduced by ethanol exposure. These
      findings suggest that ethanol-induced alterations in BDNF availability and in its
      receptor function might impair intracellular signaling pathways involved in cell
      survival, growth, and differentiation, leading to enhanced natural cell death
      during cerebral cortex development.

PMID- 11948667
TI  - Protective effect of apolipoprotein E against ischemic neuronal injury is
      mediated through antioxidant action.
AB  - Recent studies have demonstrated that apolipoprotein E (APOE) deficiency worsened
      neuronal injuries after transient focal and global cerebral ischemia. However,
      the molecular mechanism underlying the protective effect of APOE remains
      uncertain, even though several mechanisms, including excitotoxicty, free
      radicals, and apoptosis, have been cited as causes of selective neuronal
      vulnerability in cerebral ischemia. In the present study, we first compared the
      vulnerability of cultured neurons prepared from APOE-knockout mice upon exposure
      to glutamate, hydrogen peroxide, and staurosporine. No significant difference in
      cell viability was observed after exposure to glutamate or staurosporine between
      APOE-deficient and wild-type mice. However, exposure to hydrogen peroxide
      significantly increased the level of cell death in APOE-deficient mice compared
      with that in wild-type mice. After transient forebrain ischemia for 12 min, APOE
      deficient mice showed more neuronal death than wild-type mice. Pretreatment of
      APOE-deficient mice with vitamin E for 2 months markedly reduced neuronal death
      caused by ischemia. The results suggest that APOE exerted its neuroprotective
      effect against ischemia through its antioxidant action but not through mitigation
      of glutamate toxicity or blocking of apoptosis.

PMID- 11948668
TI  - Arctigenin protects cultured cortical neurons from glutamate-induced
      neurodegeneration by binding to kainate receptor.
AB  - We previously reported that arctigenin, a lignan isolated from the bark of
      Torreya nucifera, showed significant neuroprotective activity against glutamate
      induced toxicity in primary cultured rat cortical cells. In this study, the mode
      of action of arctigenin was investigated using primary cultures of rat cortical
      cells as an in vitro system. Arctigenin significantly attenuated glutamate
      induced neurotoxicity when added prior to or after an excitotoxic glutamate
      challenge. The lignan protected cultured neuronal cells more selectively from
      neurotoxicity induced by kainic acid than by N-methyl-D-aspartate. The binding of
      [(3)H]-kainate to its receptors was significantly inhibited by arctigenin in a
      competitive manner. Furthermore, arctigenin directly scavenged free radicals
      generated by excess glutamate and successfully reduced the level of cellular
      peroxide in cultured neurons. These results suggest that arctigenin exerted
      significant neuroprotective effects on glutamate-injured primary cultures of rat
      cortical cells by directly binding to kainic acid receptors and partly scavenging
      of free radicals.

PMID- 11948669
TI  - GABA(B) receptor gene expression is not altered in cocaine-sensitized rats.
AB  - Recent behavioral and neurobiological data indicate that GABA(B) receptor
      transmission is involved in cocaine-induced hyperactivity and reinforcement.
      GABA(B) receptor gene expression in cocaine-sensitized rats was examined in this
      study. Rats were injected with cocaine (15 mg/kg, daily, i.p.) or saline for 5
      consecutive days, and challenged with the same dose of cocaine after a 1-, or 20
      day hiatus. The locomotor activities of rats were recorded after challenge, and
      the rats were killed 24 hr later. GABA(B)R1a, 1b, and GABA(B)R2 mRNA in discrete
      brain regions was detected by RPA and In Situ Hybridization; GABA(B)R1a protein
      was measured by Western blotting. Rats pretreated with cocaine developed a
      hyperactivity to the cocaine challenge after a 1-day or 20-day hiatus, but
      GABA(B)R subunit mRNA and GABA(B)R1a protein densities in the targeted regions
      showed no significant difference compared to those in control rats. These data
      indicate that GABA(B) receptor gene expression is not necessarily relevant to the
      behavioral sensitization of cocaine.

PMID- 11948670
TI  - Timing the doxycycline yields different patterns of genomic recombination in
      brain neurons with a new inducible Cre transgene.
AB  - We have developed a transgenic mouse expressing the Cre recombinase under control
      of a tetracycline-responsive promoter. Using a CamKIIalpha-driven tTA transgenic
      strain and a lacZ reporter mouse, we obtained the expected neuronal pattern of
      recombination in the olfactory lobe, cortex, striatum, hippocampus and Purkinje
      cells. Moreover, recombination can be completely abolished by feeding the mice
      doxycycline in their drinking water. We also show that it is possible to get a
      different pattern of recombination by changing the timing of the doxycycline
      mediated shutdown of Cre expression. By starting the doxycycline treatment at
      birth, we restrict recombination to striatum only. This approach should be
      applicable to other inducible transgenic strains, thus increasing the number of
      available tissue-specific patterns for conditional knockouts. Also, our tetO-Cre
      transgene can be combined with any of the increasing number of tetracycline
      transactivator transgenic strains to direct specifically inducible genomic
      recombination to several areas of the brain.

PMID- 11948671
TI  - The dorsal compartment locomotory control system in amphioxus larvae.
AB  - Amphioxus myotomes consist of separate sets of superficial and deep muscle
      fibers, each with its own innervation, that are thought to be responsible for
      slow swimming and escape behavior, respectively. Tracings from serial EM sections
      of the anterior nerve cord in the larva show that the motoneurons and premotor
      interneurons controlling the superficial fibers (the dorsal compartment, or DC
      pathway) are linked by specialized junctions of a previously undescribed type,
      referred to here as juxta-reticular (JR) junctions for the characteristic
      presence of a cisterna of endoplasmic reticulum on each side. JR junctions link
      the DC motoneurons with each other, with the largest of the anterior paired
      neurons (LPN3s) and with one class of ipsilateral projection neurons (IPNs), but
      occur nowhere else. Because of the paucity of synaptic input to the DC system,
      larval behavior can only be explained if the JR junctions act as functional links
      between cells. An analysis of the pattern of cell contacts also suggests that the
      LPN3s are probably pacemakers for both slow and fast locomotion, but act through
      junctions in the former case and conventional synapses in the latter. The only
      major synaptic input to the DC system identified in somites 1 and 2 was from four
      neurons located in the cerebral vesicle, referred to here as Type 2
      preinfundibular projection neurons (PPN2s). They have unusually large
      varicosities, arranged in series, that make periodic contacts with the DC
      motoneurons. More caudally, the DC motoneurons receive additional input via
      similar large varicosities from the receptor cells of the first dorsal ocellus,
      located in somite 5. The overall circuitry of the locomotory control system
      suggests that the PPN2s may be instrumental in sustaining slow swimming, whereas
      mechanical stimulation, especially of the rostrum, preferentially activates the
      fast mode.

PMID- 11948672
TI  - Ultrastructure of the reproductive system of the black swamp snake (Seminatrix
      pygaea). III. Sexual segment of the male kidney.
AB  - In mature male snakes and lizards, a distal portion of the nephron is
      hypertrophied in relation to its appearance in females and immature males. This
      sexual segment of the male kidney apparently provides seminal fluid that is mixed
      with sperm and released into the female cloaca during copulation. In this
      article, we provide the first study at the ultrastructural level of seasonal
      variation in the sexual segment of the kidney of a squamate, the natricine snake
      Seminatrix pygaea. Previous workers have indicated that the sexual segment is
      secretory only when the testes are spermatogenically active. The sexual segment
      of the kidney in S. pygaea does not go through an extended period of inactivity
      but does show a cycle of synthesis and secretion that can be related to the
      spermatogenic cycle and mating activity. We show that synthesis of secretory
      product is initiated with the onset of spermatogenic activity in the spring and
      culminates with completion of spermiation in the fall. Secretion of the product,
      however, occurs in a premating period in March when the testes are inactive.
      Secretion during this premating period is probably necessary to provide time for
      the passage of the products down the ureter in order to mix with sperm during
      mating later in spring.

PMID- 11948673
TI  - Variation in eggshell characteristics and in intrauterine egg retention between
      two oviparous clades of the lizard Lacerta vivipara: insight into the oviparity
      viviparity continuum in squamates.
AB  - The concept of the oviparity-viviparity continuum refers to the wide range in the
      length of intrauterine egg retention and, hence, in the stage of embryonic
      development at oviposition existing in squamates. The evolutionary process
      underlying this continuum may involve not only a lengthening of egg retention in
      utero, but also a marked reduction in the thickness of the eggshell. The idea
      that there may exist a negative correlation between the developmental stage
      reached by the embryo at oviposition and the eggshell thickness within squamates,
      although supported by the comparison of oviparous vs. viviparous species, has
      seldom been evaluated by comparing eggshell thickness of oviparous forms with
      different lengths of intrauterine egg retention. Eggs of two distinct oviparous
      clades of the lizard Lacerta vivipara were compared. The eggs laid by females
      from Slovenian and Italian populations have thicker eggshells, contain embryos on
      average less developed at the time of oviposition, and require a longer
      incubation period before hatching than the eggs laid by females from French
      oviparous populations. Our data and several other examples available from the
      literature support the idea that the lengthening of intrauterine retention of
      eggs and the shortening of the subsequent external incubation of eggs are
      associated with reduction in the thickness of the eggshell, at least in some
      lineages of oviparous squamates. The current hypotheses that may account for this
      correlation are presented and a few restrictions and refinements to those
      hypotheses are discussed. In particular, other changes, such as increased
      vascularization of the oviduct and of the extraembryonic membranes, may play the
      same role as the decrease of eggshell thickness in facilitating prolonged
      intrauterine egg retention in squamates. Future studies should also consider the
      hypothesis that the length of intrauterine retention might directly depend on the
      extent of maternal-fetal chemical communication through the eggshell barrier.

PMID- 11948674
TI  - Placentation in garter snakes: scanning EM of the placental membranes of
      Thamnophis ordinoides and T. sirtalis.
AB  - Surface topography and cross-sections of the placental membranes were examined by
      scanning electron microscopy in two species of Thamnophis. The chorionic
      epithelium of the chorioallantoic placenta consists of broad, squamous cells that
      lack surface specializations. The apposed uterine epithelium contains ciliated
      cells and larger, nonciliated cells. Neither the epithelium of the chorion nor
      that of the uterus is eroded; thus, underlying capillaries are not exposed to the
      luminal surface. In both the omphaloplacenta and the omphalallantoic placenta,
      epithelium of the omphalopleure consists of brush-border cells bearing prominent
      microvilli, interspersed with cells bearing minuscule microvilli. These surface
      epithelial cells are joined at their apices and their lateral surfaces are
      extensively sculpted by intercellular channels, presenting the appearance of an
      epithelium specialized for absorption. Deep to the epithelium lie the yolk
      spheres of the isolated yolk mass, interspersed with endodermal cells. Surface
      topography of the uterine epithelia of the omphaloplacenta and omphalallantoic
      placenta is relatively unspecialized. The acellular shell membrane separates
      maternal and fetal tissues in each of the three placental types. Marked
      differences in surface features of the chorioallantois and omphalopleure probably
      reflect different roles of these membranes in gas exchange and transfer of water
      and nutrients.

PMID- 11948675
TI  - Comparative morphological assessment of the psyllid pleuron (Insecta, Hemiptera,
      Sternorrhyncha).
AB  - A unique set of morphological characters based on the hemipteran (sensu lato)
      thorax are used to define the pleuron of Psylloidea. New external and internal
      topographical descriptions of pleurites of all three thoracic segments are
      provided based on observations of specimens from various genera representing the
      current taxonomic arrangement of Psylloidea. Variations in propleurite morphology
      and the anteroventral angle of the episternum among taxa are clarified. The
      mesothoracic pleural sulcus is found to be a distinct groove formed by the deep
      fossa of the pleural apophysis and is not a secondary structure, as assigned by
      previous authors. A newly discovered internal apodeme of the metathoracic
      trochantin and a serially homologous structure in the mesothorax isolate the
      trochantinal territory of the second segment. The metathoracic pleural sulcus
      appears to be pressed against the ventral edge of the metepimeron, as previously
      described for the mesothorax of certain species of other insects having a
      strongly developed meron. Use of morphological interpretations and newly
      discovered apodemes to assess primary homology of structures for phylogenetic and
      taxonomic studies is discussed. A glossary of standardized morphological terms
      for thoracic structures of non-heteropteran Hemiptera based on this study and
      other recent and former dissertations on the insect thorax is provided.

PMID- 11948676
TI  - How tubular venom-conducting fangs are formed.
AB  - Elapids, viperids, and some other groups of colubroid snakes have tubular fangs
      for the conduction of venom into their prey. The literature describing the
      development of venom-conducting fangs provides two contradictory accounts of fang
      development. Some studies claim that the venom canal forms by the infolding of a
      deep groove along the surface of the tooth to produce an enclosed canal. In other
      works the tubular fang is said to form by the deposition of material from tip to
      base, so that the canal develops without any folding. This study was undertaken
      to examine fang development and to account for the disagreement in the literature
      by determining whether fang formation varies among groups of venomous snakes and
      whether it differs between embryos and adults. Adult and embryonic
      representatives of elapids and viperids were examined. All fangs examined, elapid
      and viperid, embryos and adults, were found to develop into their tubular shape
      by the addition of material to the basal end of the tooth rather than by the
      folding inward of an ungrooved tooth to form a tubular fang. In some cases, the
      first fang that develops in embryonic snakes differs morphologically from all
      those formed subsequently.

PMID- 11948677
TI  - Head structures of Priacma serrata Leconte (Coleptera, Archostemata) inferred
      from X-ray tomography.
AB  - Internal and external features of the head of Priacma serrata were studied with X
      ray microtomography and with histological methods. The comparison of both
      techniques shows that X-ray tomography is a promising new technique for the
      investigation of insect anatomy. The still somewhat coarse resolution of the X
      ray data is compensated for by advantages like the nondestructive and artifact
      free data acquisition. The head of P. serrata and other adults of Archostemata is
      characterized by many derived features. Muscular features of Priacma, especially
      muscles of the labium and pharynx, differ strongly from what is found in other
      groups of Coleoptera. Several character states are considered as autapomorphies
      of Archostemata: scale-like surface structures, constricted neck, strongly
      reduced tentorium, and the plate-like, enlarged prementum. The scales provide a
      protecting surface pattern and may have evolved with a more exposed lifestyle.
      The enlarged prementum forms a lid, which closes the mouth and covers the ligula
      when it is pulled back by contraction of the unusually strong submento-premental
      muscle. The presence of four cone-shaped protuberances on the dorsal side of the
      head is considered an autapomorphy of Cupedidae. The galea with a narrow stalk
      and a round and pubescent distal galeomere is another autapomorphy of this
      family. It has probably evolved as an adaptation to pollen-feeding. The shape of
      the mandible of Cupedidae is plesiomorphic compared to what is found in adults of
      Ommatidae. The vertical arrangement of apical teeth is an autapomorphy of the
      latter family. The lateral insertion of the antenna in Priacma is a groundplan
      feature of Cupedidae. The dorsal shift is a synapomorphy of all other cupedid
      genera. A cladistic analysis of characters of the head and additional data
      resulted in the following branching pattern: ((Crowsoniella + (Omma +
      Tetraphalerus)) + (Micromalthus + (Priacma + (Paracupes + (Cupes + Tenomerga +
      Prolixocupes + Rhipsideigma + Distocupes + (Adinolepis + Ascioplaga)))))).

PMID- 11948678
TI  - Possible ctenophoran affinities of the Precambrian "sea-pen" Rangea.
AB  - The Namibian Kuibis Quartzite fossils of Rangea are preserved three-dimensionally
      owing to incomplete collapse of the soft tissues under the load of
      instantaneously deposited sand. The process of fossilization did not reproduce
      the original external morphology of the organism but rather the inner surface of
      collapsed organs, presumably a system of sacs connected by a medial canal. The
      body of Rangea had tetraradial symmetry, a body plan shared also by the White Sea
      Russian fossil Bomakellia and possibly some other Precambrian frond-like fossils.
      They all had a complex internal anatomy, smooth surface of the body, and radial
      membranes, making their alleged colonial nature unlikely. Despite a different
      style of preservation, the Middle Cambrian Burgess Shale frond-like Thaumaptilon
      shows several anatomical similarities to Rangea. The body plan of the Burgess
      Shale ctenophore Fasciculus, with its numerous, pinnately arranged comb organs,
      is in many respects transitional between Thaumaptilon and the Early Cambrian
      ctenophore Maotianoascus from the Chengjiang fauna of South China. It is proposed
      that the irregularly distributed dark spots on the fusiform units of the petaloid
      of Thaumaptilon represent a kind of macrocilia and that the units are homologous
      with the ctenophoran comb organs. These superficial structures were underlain by
      the complex serial organs, well represented in the fossils of Rangea. The
      Precambrian "sea-pens" were thus probably sedentary ancestors of the ctenophores.

PMID- 11948679
TI  - Parathyroid hormone (hPTH 1-38) stimulates the expression of UBP41, an ubiquitin
      specific protease, in bone.
AB  - Parathyroid hormone (PTH) stimulates bone formation in both animals and humans,
      and the expression of a number of genes has been implicated in the mediation of
      this effect. To discover new bone factors that initiate and support this
      phenomenon, we used differential display reverse transcription polymerase chain
      reaction (DDRT-PCR) and screened for genes, which are differentially expressed in
      osteoblast-enriched femoral metaphyseal primary spongiosa of young male rats
      after a single subcutaneous (s.c.) injection of hPTH (1-38) (8 microg/100 g). We
      found and cloned one full-length cDNA, which encodes a putative 348 amino acid
      protein. Sequence analysis of this protein demonstrates a 98, 93.7, and 82.5%
      identity with mouse, human, and chicken ubiquitin-specific protease UBP41,
      respectively. Northern blot analysis confirmed that a 3.8-4 kb UBP41 mRNA
      transcript was rapidly increased 1 h after acute hPTH (1-38) exposure in both
      metaphyseal (6- to 8-fold) and diaphyseal (3-fold) bone, but returned to control
      levels by 24 h after exposure. In contrast, continuous exposure to hPTH (1-38),
      resulted in a rapid and sustained elevation of UBP41 mRNA. PTH (1-31), which
      stimulates intracellular cAMP, and PTHrP (1-34) both induced UBP41 mRNA
      expression; whereas PTH analogs (3-34) and (7-34), that do not stimulate cAMP,
      had no effect on UBP41 expression. UBP41 mRNA expression was also rapidly induced
      1 h after injection of PGE2, but returned to the control level by 6 to 24 h. In
      vitro, UBP41 mRNA is expressed in primary osteoblasts (metaphyseal and diaphyseal
      derived) and in the osteoblast-like cell lines UMR106, ROS17/2.8, and BALC. PTH
      (1-38) treatment induced UPB41 expression (3.6- to 13-fold) in both primary
      cultures of osteoblasts and in UMR106 cells. Further analysis in UMR 106 cells
      demonstrated that PGE2, forskolin and dibutyryl cAMP increased UBP41 mRNA
      expression 4-, 4.5-, and 2.4-fold, respectively. Tissue distribution analysis of
      UBP41 mRNA detected transcripts in brain, heart, skeletal muscle, kidney, liver,
      and testis. Together, these results demonstrate that UBP41, an ubiquitin-specific
      protease, is selectively upregulated in bone by the osteotropic agents PTH,
      PTHrP, and PGE2, possibly via the PKA/cAMP pathway. We speculate that the rapid
      induction of UBP41 in response to these physiological regulators contributes to
      the mechanism by which either the structure, activity, half-life or localization
      of essential proteins are modified to maintain bone homeostasis.

PMID- 11948680
TI  - Protein nucleation and crystallization by homologous protein thin film template.
AB  - A new method of protein nucleation and crystallization based on Langmuir-Blodgett
      technology is here utilized for the template stimulation of crystal growth of so
      far non-crystallized proteins. Microcrystals (60-120 microm) of bovine cytochrome
      P450scc and human protein kinase CKII alpha subunit were obtained with use of the
      homologous protein thin film template by vapor diffusion modified hanging drop
      method. The induction of microcrystals nucleation by the thin template confirms
      in the two different important classes of proteins, until now never crystallized,
      the positive stimulatory influence for crystal formation of protein thin film
      template, which was observed in an earlier study with a model system (chicken egg
      white lysozyme) as an unexpected acceleration and enhancement in the crystal
      growth.

PMID- 11948683
TI  - Nucleolin is a calcium-binding protein.
AB  - We have purified a prominent 110-kDa protein (p110) from 1.6 M NaCl extracts of
      rat liver nuclei that appears to bind Ca2+. p110 was originally identified by
      prominent blue staining with 'Stains-All' in sodium dodecyl sulfate
      polyacrylamide gels and was observed to specifically bind ruthenium red and
      45Ca2+ in nitrocellulose blot overlays. In spin-dialysis studies, purified p110
      saturably bound approximately 75 nmol Ca2+/mg protein at a concentration of 1 mM
      total Ca2+ with half-maximal binding observed at 105 microM Ca2+. With
      purification, p110 became increasingly susceptible to proteolytic (likely
      autolytic) fragmentation, although most intermediary peptides between 40 and 90
      kDa retained "Stains-All", ruthenium red, and 45Ca2+ binding. N-terminal
      sequencing of intact p110 and a 70-kDa autolytic peptide fragment revealed a
      strong homology to nucleolin. Two-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE)/IEF revealed autolysis produced
      increasingly acidic peptide fragments ranging in apparent pI's from 5.5 for
      intact p110 to 3.5 for a 40 kDa peptide fragment. Intact p110 and several peptide
      fragments were immunostained with a highly specific anti-nucleolin antibody,
      R2D2, thus confirming the identity of this protein with nucleolin. These annexin
      like Ca2+-binding characteristics of nucleolin are likely contributed by its
      highly acidic argyrophilic N-terminus with autolysis apparently resulting in
      largely selective removal of its basic C-terminal domain. Although the Ca2+
      dependent functions of nucleolin are unknown, we discuss the possibility that
      like the structurally analogous HMG-1, its Ca2+-dependent actions may regulate
      chromatin structure, possibly during apoptosis.

PMID- 11948681
TI  - Cortisol regulates the expression of Notch in osteoblasts.
AB  - Glucocorticoids have important effects on osteoblastic replication,
      differentiation, and function, and the Notch family of receptors is considered to
      play a role in osteoblastic cell differentiation. We postulated that cortisol
      could regulate Notch and Notch ligand expression in osteoblastic cells, providing
      an additional mechanism by which glucocorticoids could regulate osteoblastic
      differentiation. We examined the expression and regulation of Notch1, 2, 3, and 4
      and their ligands Jagged 1 and 2 and Delta 1 and 3 by cortisol in cultures of
      osteoblastic MC3T3-E1 cells. Cortisol caused a time-dependent increase in Notch1
      and 2 mRNA levels in MC3T3 cells. Notch3 and 4 were not detected in the presence
      or absence of cortisol. MC3T3 cells expressed Delta 1 and Jagged 1 but not Jagged
      2 or Delta 3 mRNAs, and cortisol did not have a substantial effect on the
      expression of any of these ligands. Cortisol increased the rate of Notch1 and 2
      transcription and, in transcriptionally arrested cells, did not modify the decay
      of the transcripts, indicating a transcriptional level of control. In conclusion,
      cortisol stimulates Notch1 and 2 transcription in osteoblasts. Since Notch
      signaling appears to play a negative role in osteoblastic differentiation, its
      increased expression could be relevant to the actions of cortisol in bone.

PMID- 11948682
TI  - Mutation in collagen gene induces cardiomyopathy in transgenic mice.
AB  - In many remodeling tissues, such as the heart, collagen degradation to provide
      new integrin-binding sites is required for survival. However, complete loss of
      integrin signaling due to disconnection from extracellular matrix (ECM) leads to
      apoptosis and dilatation. To test the hypothesis that a mutation in type I
      collagen gene induces cardiomyopathy, we employed a metalloproteinase-resistant
      collagen mutant homozygous transgenic male (B6,129-Colla-1) and compared with age
      sex matched wildtype C57BL/J6 control mice. At the age of 38-42 weeks, aortic and
      left ventricle (LV) pressure were measured. The LV wall thickness and diameter
      were measured by a digital micrometer. The levels of matrix metalloproteinase-2
      (MMP-2) activity and cardiospecific tissue inhibitor of metalloproteinase-4 (TIMP
      4) were measured by zymography and Western blot analyses, respectively. The
      levels of collagenolysis were measured by Western blot using anti-collagen
      antibody. In transgenic and wildtype mice, end-diastolic pressure (EDP) was 8.3
      +/- 1.7 and 6.5 +/- 1.1 mmHg; LV diameter was 3.43 +/- 0.07 and 2.94 +/- 0.05 mm;
      wall thickness was 1.18 +/- 0.03 and 1.28 +/- 0.04 mm; end-diastolic wall stress
      was 600 +/- 158 and 347 +/- 49 dynes/cm(2), respectively. The increase in LV wall
      stress was associated with increased MMP-2 activity, increased collagenolysis,
      and decreased levels of TIMP-4. This leads to reduced elastic compliance in
      collagen mutant transgenic mice. The occurrence of cardiomyopathy in adult Colla
      1 mice may be a significant confounding factor as it may be indicative of
      increased basal levels of ECM disruption. This phenotype is what would be
      expected if collagen degradation normally supplies integrin ligands during
      cardiac muscle remodeling.

PMID- 11948684
TI  - Prolonged culture of HOS 58 human osteosarcoma cells with 1,25-(OH)2-D3, TGF
      beta, and dexamethasone reveals physiological regulation of alkaline phosphatase,
      dissociated osteocalcin gene expression, and protein synthesis and lack of
      mineralization.
AB  - Cultured rodent osteoblastic cells reiterate the phenotypic differentiation and
      maturation of osteoblasts seen in vivo. As previously shown, the human
      osteosarcoma cell line HOS 58 represents a differentiated stage of osteoblast
      development. The potential of HOS 58 for still further in vitro differentiation
      suggests the line can serve as a model of osteoblast maturation. Using this cell
      line, we have investigated the influence of 1,25-(OH)2-D3 (D3), TGF-beta and
      Dexamethasone (Dex) on proliferation and on the protein and mRNA levels of
      alkaline phosphatase (AP), procollagen 1 (Col 1), and osteocalcin (Oc), as well
      as mineralization during 28 days in culture. AP mRNA and protein were highly
      expressed throughout the culture period with further increase of protein AP
      activity at constant gene expression levels. A differentiation inhibiting effect
      of either TGF-beta or Dex was seen. Col 1 was investigated without the use of
      ascorbic acid and showed only minor changes during culture time or stimulation.
      The gene expression for Oc increased continually whereas protein synthesis peaked
      at confluence and decreased thereafter. TGF-beta and Dex treatments decreased Oc
      mRNA and protein levels. Stimulation by D3 was maximal at day 7 with a decrease
      thereafter. HOS 58 cells showed no mineralization capacity when stimulated with
      different agents, as measured by energy-dispersive X-ray microanalysis. This was
      not due to absence of Cbfa1 expression. In conclusion, the HOS 58 osteosarcoma
      cell line represents a differentiated cell line with highly expressed and
      physiologically regulated AP expression during further differentiation in
      culture. We observed a dissociation between osteocalcin gene expression and
      protein secretion which may contribute to the lack of mineralization in this cell
      line.

PMID- 11948685
TI  - Tissue inhibitor of metalloproteinases-4 (TIMP-4) gene expression is increased in
      human osteoarthritic femoral head cartilage.
AB  - Tissue inhibitor of metalloproteinases-4 (TIMP-4), the newest member of the TIMP
      family, blocks the activities of several matrix metalloproteinases (MMPs)
      implicated in the arthritic cartilage erosion. By utilizing semi-quantitative RT
      PCR, immunoblotting, and immunohistochemistry, we investigated whether the TIMP-4
      gene is expressed in human non-arthritic and osteoarthritic (OA) cartilage.
      Directly analyzed femoral head cartilage showed TIMP-4 RNA expression in 2 of 9
      non-arthritic and 12 of 14 OA patients. Femoral head cartilage from 6 of 9 OA
      patients had elevated TIMP-4 protein compared to the low-level expression in 3 of
      8 non-arthritic controls. In most patients, there was correlation between TIMP-4
      RNA and protein expression. TIMP-4 protein was also detected
      immunohistochemically in the upper zone of OA cartilage. The widespread TIMP-4
      RNA and protein expression and augmentation in femoral OA cartilage suggests its
      important role in joint tissue remodeling and pathogenesis of OA. Increased TIMP
      levels in arthritic cartilage may not be a sufficiently effective defense against
      cartilage resorption by excessive multiple MMPs and aggrecanases.

PMID- 11948686
TI  - Role of mTOR in the degradation of IRS-1: regulation of PP2A activity.
AB  - We have investigated the role of PI 3-kinase and mTOR in the degradation of IRS-1
      induced by insulin. Inhibition of mTOR with rapamycin resulted in approximately
      50% inhibition of the insulin-induced degradation of IRS-1. In contrast,
      inhibition of PI-3 kinase, an upstream activator of mTOR, leads to a complete
      block of the insulin-induced degradation. Inhibition of either PI-3 kinase or
      mTOR prevented the mobility shift in IRS-1 in response to insulin, a shift that
      is caused by Ser/Thr phosphorylation. These results indicate that insulin
      stimulates PI 3-kinase-mediated degradation of IRS-1 via both mTOR-dependent and 
      independent pathways. Platelet-derived growth factor (PDGF) stimulation leads to
      a lower level of degradation, but significant phosphorylation of IRS-1. Both the
      degradation and phosphorylation of IRS-1 in response to PDGF are completely
      inhibited by rapamycin, suggesting that PDGF stimulates IRS-1 degradation
      principally via the mTOR-dependent pathway. Inhibition of the serine/threonine
      phosphatase PP2A with okadaic acid also induced the phosphorylation and
      degradation of IRS-1. IRS-1 phosphorylation and degradation in response to
      okadaic acid were not inhibited by rapamycin, suggesting that the action of mTOR
      in the degradation of IRS-1 results from inhibition of PP2A. Consistent with
      this, treatment of cells with rapamycin stimulated PP2A activity. While the role
      of mTOR in the phosphorylation of IRS-1 appears to proceed primarily through the
      regulation of PP2A, we also provide evidence that the regulation of p70S6 kinase
      phosphorylation requires the direct activity of mTOR.

PMID- 11948687
TI  - Tubulin, actin, and tau protein interactions and the study of their
      macromolecular assemblies.
AB  - The intracellular polymerization of cytoskeletal proteins into their
      supramolecular assemblies raises many questions regarding the regulatory patterns
      that control this process. Binding experiments using the ELISA solid phase
      system, together with protein assembly assays and electron microscopical studies
      provided clues on the protein-protein associations in the polymerization of
      tubulin and actin networks. In vitro reconstitution experiments of these
      cytoskeletal filaments using purified tau, tubulin, and actin proteins were
      carried out. Tau protein association with tubulin immobilized in a solid phase
      support system was inhibited by actin monomer, and a higher inhibition was
      attained in the presence of preassembled actin filaments. Conversely, tubulin and
      assembled microtubules strongly inhibited tau interaction with actin in the solid
      phase system. Actin filaments decreased the extent of in vitro tau-induced
      tubulin assembly. Studies on the morphological aspects of microtubules and actin
      filaments coexisting in vitro, revealed the association between both cytoskeletal
      filaments, and in some cases, the presence of fine filamentous structures
      bridging these polymers. Immunogold studies showed the association of tau along
      polymerized microtubules and actin filaments, even though a preferential
      localization of labeled tau with microtubules was revealed. The studies provide
      further evidence for the involvement of tau protein in modulating the
      interactions of microtubules and actin polymers in the organization of the
      cytsokeletal network.

PMID- 11948688
TI  - Nuclear localization and DNA interaction of protein disulfide isomerase ERp57 in
      mammalian cells.
AB  - Protein disulfide isomerase ERp57 is localized predominantly in the endoplasmic
      reticulum, but is also present in the cytosol and, according to preliminary
      evidence, in the nucleus of avian cells. Conclusive evidence of its nuclear
      localization and of its interaction with DNA in vivo in mammalian cells is
      provided here on the basis of DNA-protein cross-linking experiments performed
      with two different cross-linking agents on viable HeLa and 3T3 cells. Nuclear
      ERp57 could also be detected by immunofluorescence in HeLa cells, where it showed
      an intracellular distribution clearly different from that of an homologous
      protein, located exclusively in the endoplasmic reticulum. Mammalian ERp57
      resembles the avian protein in its recognition of S/MAR-like DNA sequences and in
      its association with the nuclear matrix. It can be hypothesized that ERp57, which
      is known to associate with other proteins, in particular STAT3 and calreticulin,
      may contribute to their nuclear import, DNA binding, or other functions that they
      fulfil inside the nucleus.

PMID- 11948689
TI  - Caspase cleavage product lacking amino-terminus of IkappaBalpha sensitizes
      resistant cells to TNF-alpha and TRAIL-induced apoptosis.
AB  - In response to a diverse array of signals, IkappaBalpha is targeted for
      phosphorylation-dependent degradation by the proteasome, thereby activating NF
      kappaB. Here we demonstrate a role of the cleavage product of IkappaBalpha in
      various death signals. During apoptosis of NIH3T3, Jurkat, Rat-1, and L929 cells
      exposed to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL),
      Fas, serum deprivation, or TNF-alpha, respectively, IkappaBalpha was cleaved in a
      caspase-dependent manner. In vitro and in vivo cleavage assays and site-directed
      mutagenesis showed that caspase-3 cleaved IkappaBalpha between Asp31 and Ser32.
      Expression of the cleavage product lacking amino-terminus (1-31),
      DeltaIkappaBalpha, sensitized otherwise resistant NIH3T3 fibroblast cells to
      apoptosis induced by TNF-alpha or TRAIL, and HeLa tumor cells to TNF-alpha.
      DeltaIkappaBalpha was more pro-apoptotic compared to wild type or cleavage
      resistant (D31E)IkappaBalpha mutant and the sensitization elicited by
      DeltaIkappaBalpha was as effective as that by the dominant negative mutant,
      (S32,36A)IkappaBalpha, in NIH3T3 cells. DeltaIkappaBalpha suppressed the
      transactivation of NF-kappaB induced by TNF-alpha or TRAIL, as reflected by
      luciferase-reporter activity. Conversely, expression of the p65 subunit of NF
      kappaB suppressed TNF-alpha-, TRAIL-, and serum deprivation-induced cell death.
      On the contrary, DeltaIkappaBalpha was less effective at increasing the death
      rate of HeLa cells that were already sensitive to death signals including TRAIL,
      etoposide, or taxol. These results suggest that DeltaIkappaBalpha generated by
      various death signals sensitizes cells to apoptosis by suppressing NF-kappaB
      activity.

PMID- 11948690
TI  - Mapping of an origin of DNA replication near the transcriptional promoter of the
      human HPRT gene.
AB  - A quantitative PCR method was used to map a functional origin of DNA replication
      in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene in normal human
      fibroblasts. This PCR method measures the abundance of specific sequences in
      short fragments of newly replicated DNA from logarithmically growing cells.
      Quantitative measurements rely on synthetic molecules (competitors) that amplify
      with the same primer sets as the target molecules, but generate products of
      different sizes. This method was first utilized to determine the position of the
      replication origin near the lamin B2 gene (Giacca et al. [1994] Proc. Natl. Acad.
      Sci. U S A. 91:7119-7123). In the present study, primer sets were tested along a
      16-kb region near exon 1 of the HPRT gene. The most abundant fragment was found
      to be located in the first intron of HPRT, just downstream of the promoter and
      exon 1 of the gene, and approximately 3.5 kb upstream of a previously reported
      autonomously replicating sequence (Sykes et al. [1988] Mol. Gen. Genet. 212:301
      309).

PMID- 11948691
TI  - VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that
      enhance VEGF165-receptor binding.
AB  - Co-expression of NRP1 and (VEGFR-2) KDR on the surface of endothelial cells (EC)
      enhances VEGF165 binding to KDR and EC chemotaxis in response to VEGF165.
      Overexpression of NRP1 by prostate tumor cells in vivo results in increased tumor
      angiogenesis and growth. We investigated the molecular mechanisms underlying NRP1
      mediated angiogenesis by analyzing the association of NRP1 and KDR. An
      intracellular complex containing NRP1 and KDR was immunoprecipitated from EC by
      anti-NRP1 antibodies only in the presence of VEGF165. In contrast, VEGF121, which
      does not bind to NRP1, did not support complex formation. Complexes containing
      VEGF165, NRP1, and KDR were also formed in an intercellular fashion by co-culture
      of EC expressing KDR only, with cells expressing NRP1 only, for example, breast
      carcinoma cells. VEGF165 also mediated the binding of a soluble NRP1 dimer to
      cells expressing KDR only, confirming the formation of such complexes.
      Furthermore, the formation of complexes containing KDR and NRP1 markedly
      increased 125I-VEGF165 binding to KDR. Our results suggest that formation of a
      ternary complex of VEGF165, KDR, and NRP1 potentiates VEGF165 binding to KDR.
      These complexes are formed on the surface of EC and in a juxtacrine manner via
      association of tumor cell NRP1 and EC KDR.

PMID- 11948692
TI  - Interferon regulatory factor-1 mediates interferon-gamma-induced apoptosis in
      ovarian carcinoma cells.
AB  - Interferon-gamma (IFN-gamma), as one of interferon family that regulates
      antiviral, antiproliferative, and immunomodulatory responses, has been implicated
      for the growth regulation of ovarian cancer cells. However, the molecular
      mechanisms are not yet fully defined. To analyze detailed mechanisms, the ovarian
      cancer cell lines (2774, PA-1, OVCAR-3, and SKOV-3) were treated with IFN-gamma.
      The growth of 2774 was most effectively suppressed than that of other cells in
      both time-course and dose-dependent experiments. The order of sensitivity in
      other cells was PA-1 >> OVCAR-3 > SKOV-3 (not responded at all). The DNA
      fragmentation and DAPI staining assays suggested that the IFN-gamma-mediated
      cytotoxicity could be triggered by apoptosis. The treatment induced IFN
      regulatory factor-1 (IRF-1) in two IFN-gamma-sensitive cells (2774, PA-1),
      whereas IRF-1 was not induced in two IFN-gamma-resistant cells (OVCAR-3, SKOV-3).
      The levels of p53 and p21WAF1 were not strikingly changed in all four cells.
      Interestingly, the expression of interleukin-converting enzyme (ICE, or caspase
      1) was increased by the treatment in a kinetically consistent manner to the
      induction of IRF-1. However, CD95 (Fas/APO-1) was not changed. Apoptosis was
      greatly induced, when IRF-1 was transiently expressed in PA-1 without the
      treatment of IFN-gamma. However, it was repressed when IRF-1 together with IRF-2,
      an antagonist of IRF-1, were coexpressed. In addition, the effect of IFN-gamma
      was reduced in the 2774 and PA-1 cells stably expressing either IRF-1 antisense
      or IRF-2 sense, as shown by the cytotoxicity and FACS analysis. Furthermore, the
      IFN-gamma-induced apoptosis was greatly reduced, when inhibitors of ICE were
      treated into PA-1 cells. Taken together, these results suggest that IRF-1
      directly mediates the IFN-gamma-induced apoptosis via the activation of caspase-1
      gene expression in IFN-gamma-sensitive ovarian cancer cells.

PMID- 11948693
TI  - Epidermal growth factor and thrombin induced proliferation of immortalized human
      keratinocytes is coupled to the synthesis of Egr-1, a zinc finger transcriptional
      regulator.
AB  - The epidermal growth factor (EGF) receptor is highly expressed in HaCaT
      keratinocytes as shown by Western blotting. Stimulation of HaCaT cells with EGF,
      and also with the serine protease thrombin, induced DNA synthesis, measured by
      incorporation of 5-bromo-2'-deoxyuridine into the DNA of proliferating cells.
      Using antibodies directed against the active form of the EGF receptor, we show
      that in HaCaT cells EGF and thrombin triggered a rapid activation of the EGF
      receptor, followed by the phosphorylation and activation of the extracellular
      signal-regulated protein kinase (ERK). Moreover, EGF and thrombin induced a
      transient synthesis of the zinc finger transcriptional regulator Egr-1.
      Proliferation, activation of ERK, and biosynthesis of Egr-1 was completely
      inhibited in EGF or thrombin-treated HaCaT cells by the MAP kinase kinase
      inhibitor PD98059 and by AG1487, an EGF receptor-specific tyrosine kinase
      inhibitor. These data indicate that phosphorylation and activation of both the
      EGF receptor and ERK are essential for mitogenic signaling via EGF and thrombin.
      The synthesis of Egr-1 in HaCaT cells as a result of EGF or thrombin stimulation
      suggests that Egr-1 may be an important "late" part of the EGF and thrombin
      initiated signaling cascades. We postulate that Egr-1 may function as a "third
      messenger" in keratinocytes connecting mitogenic stimulation with changes in gene
      transcription.

PMID- 11948694
TI  - Drosophila NO-dependent guanylyl cyclase is finely regulated by sequential order
      of coincidental signaling.
AB  - We investigate the mechanism of regulation of Drosophila-soluble guanylate
      cyclase. Multiple putative sites of phosphorylation for the major kinases are
      present on both subunits of the heterodimer. We show that NO activation after
      binding to the heme group, is specifically modulated by sequential
      phosphorylations. PKA increases the NO stimulation at optimum level when both
      subunits are phosphorylated. Phosphorylation by CK (casein kinase-like) first,
      inhibits the PKA phosphorylation of the alpha subunit and limits the PKA
      upregulation of the cyclase activity. However, PKA phosphorylation first didn't
      prevent CK phosphorylation of the two subunits and the sequence PKA/CK induces
      higher level of NO activation than CK/PKA. These phosphorylations occur
      independently of NO binding and the direct inhibitory effect of calcium is
      observed for all the sCG forms. These data show that the sGC activity is
      regulated in a complex way, and the well-known asymmetry of the two subunits
      appears to cause the reading of the sequence of regulatory signals. This
      qualifies sGC as molecular detector on which converge coincidental and/or
      sequential neuronal signals. Furthermore, due to the fact that NO induction is
      huge (more than 600-fold obtained with the mammal counterpart), we might consider
      that any variation in kinases activation and/or calcium concentration in micro
      area of neuronal processes, provokes locally significant quantitative difference
      of cGMP synthesis in presence of diffusing NO.

PMID- 11948695
TI  - Smoothelin contains a novel actin cytoskeleton localization sequence with
      similarity to troponin T.
AB  - Smoothelin, a cytoskeletal protein, exists in a large isoform specifically
      expressed in vascular smooth muscle cells, and a small visceral isoform generated
      by a downstream transcriptional start site. Using fusions to the green
      fluorescent protein, we could show that both smoothelin isoforms are localized at
      actin containing filaments and mapped two domains that are each sufficient for
      localization at the actin cytoskeleton. The first domain is located in the
      vascular-specific, N-terminal half of smoothelin and the second in the common, C
      terminal half. The second domain shares clear sequence similarity with a domain
      of troponin T involved in actin filament association. These results suggest that
      the tissue-specific expression of smoothelin isoforms might contribute to the
      different contractile properties of smooth muscle cells.

PMID- 11948696
TI  - Functional expression of human heme oxygenase-1 (HO-1) driven by HO-1 promoter in
      vitro and in vivo.
AB  - We developed a retrovirus-mediated human heme oxygenase-1 (HO-1) gene expression
      system and assessed the impact of heme on the inducibility of the HO-1 gene in
      rat lung microvessel (RLMV) endothelial cells and in newborn Sprague-Dawley (SD)
      rats. Overexpression of the HO-1 gene driven by HO-1 promoter (HOP) resulted in
      an increase in HO-1 protein and HO activity by 4.8- and 1.3-fold, respectively,
      compared to the viral LTR promoter. The increased HO-1 gene expression was
      associated with the enhancement of CO production. In cells transduced by HOP
      driven HO-1 gene, there was a decrease in basal cyclooxygenase (COX) activity as
      measured by PGE(2). The degree of HO-1 expression and, consequently, the levels
      of cellular heme were directly related to COX activity. Supplementation with heme
      markedly increased PGE(2) and cGMP synthesis. In all (6/6) of newborn SD rats
      injected with retrovirus LSN-HOP-HO-1, both HO-1 and neo(r) transcripts were
      expressed in tissues. We hypothesize that degree of HO-1 gene expression resulted
      in a differential rate of cellular heme-dependent enzyme gene expression, which
      may play a vital role in maintaining cellular homeostasis.

PMID- 11948697
TI  - Reversible hypercondensation and decondensation of mitotic chromosomes studied
      using combined chemical-micromechanical techniques.
AB  - We show that the chromatin in mitotic chromosomes can be drastically
      overcompacted or unfolded by temporary shifts in ion concentrations. By locally
      'microspraying' reactants from micron-size pipettes, while simultaneously
      monitoring the size of and tension in single chromosomes, we are able to
      quantitatively study the dynamics of these reactions. The tension in a chromosome
      is monitored through observation and calibration of bending of the glass pipettes
      used to manipulate the chromosomes. For concentrations > 500 mM of NaCl and > 200
      mM of MgCl2, we find that the initially applied tensions of approximately 500 pN
      relax to zero and that mitotic chromatin temporarily disperses in agreement with
      previous work (Maniotis et al. [1997] J. Cell. Biochem. 65:114-130). This
      unfolding occurs in about 1 s, and is reversible once the charge density is
      returned to physiological levels, if the exposure is not longer than
      approximately 1 min. Low concentrations of NaCl (< 30 mM) also induces a decrease
      in tension and increase in size. We observe this swelling to be isotropic in
      experiments on chromosomes under zero tension, a behavior inconsistent with the
      existence of a well-defined central chromosome 'scaffold'. By contrast 10 mM of
      divalent cations (MgCl2 and CaCl2) induces an extremely rapid and reversible
      increase in tension and a reduction in the size of mitotic chromosomes.
      Hexaminecobalt trichloride (trivalent cation) has the same effect as MgCl2 and
      CaCl2, except the magnitude of force increase and size change are much larger.
      Hexaminecobalt trichloride reduces mitotic chromosomes to 65% of their original
      volume, indicating that at least 1/3 of their apparent volume is aqueous
      solution. These results indicate that chromatin inside mitotic chromatids has a
      large amount of conformational freedom allowing dynamic unfolding and refolding
      and that charge interactions play a central role in maintaining mitotic
      chromosome structure.

PMID- 11948699
TI  - Prospective investigation of a subcutaneous, implantable central venous access
      device for therapeutic plasma exchange in adults with neurological disorders.
AB  - Standard alternatives to antecubital access for long-term therapeutic plasma
      exchange, including percutaneous polyurethane or tunneled silicone catheters, are
      associated with complications and inconvenience for the patient. We have
      investigated the Bard CathLink 20, a subcutaneously implantable central venous
      access device, as an alternative for outpatient plasma exchange. The CathLink 20
      consists of a funnel-shaped titanium port connected to a soft polyurethane
      derived catheter and is accessed percutaneously using an 18-gauge catheter-over
      needle Angiocath. Six patients with paraproteinemic polyneuropathies underwent 64
      outpatient plasma exchanges using the CathLink 20 for access, 31 using 2 CathLink
      20's (draw and return), 20 using a single CathLink 20 as the draw site and 13
      using a single CathLink 20 as the return site. Mean (+/- SD) plasma removed was
      3,680 +/- 551 ml in 115.2 +/- 25.3 min. Apheresis personnel were able to access
      the ports in 1.23 +/- 0.6 attempts per port per procedure. Six of 70 planned
      procedures were aborted: 3 because of failure of an antecubital access site and 3
      because of catheter occlusion resolved using a thrombolytic agent. Whole blood
      flow rate was approximately 54 ml/min, and plasma flow rate was about 32 ml/min
      for 135 min. Access pressures were stable at -150 to -200 torr (P = 0.1395).
      Return line pressures varied between 90 and 130 torr (P = 0.0147). No patient
      required hospitalization during the study. Though not optimized for apheresis,
      the CathLink 20 provides a reasonable option for chronic apheresis patients who
      lack adequate peripheral venous access.

PMID- 11948698
TI  - Isolation of baculovirus-expressed human vitamin D receptor: DNA responsive
      element interactions and phosphorylation of the purified receptor.
AB  - Two controversial aspects in the mechanism of human vitamin D receptor (hVDR)
      action are the possible significance of VDR homodimers and the functional role of
      receptor phosphorylation. To address these issues, milligram quantities of
      baculovirus-expressed hVDR were purified to 97% homogeneity, and then tested for
      binding to the rat osteocalcin vitamin D responsive element (VDRE) via
      electrophoretic mobility shift and half-site competition assays in the presence
      or absence of a CV-1 nuclear extract containing retinoid X receptor (RXR).
      Methylation interference analysis revealed that both the hVDR homodimer and the
      VDR-RXR heterodimer display similar patterns of VDRE G-base protection. However,
      in competition studies, the relative dissociation of the homodimeric hVDR complex
      from the VDRE was extremely rapid (t1/2 < 30 s) compared to the dissociation of
      the heteromeric complex (t1/2 > 5 min), thus illustrating the relative
      instability and low affinity of homodimeric VDR binding to DNA. These results
      indicate that VDR-RXR heterodimers are the preferred VDRE binding species.
      Further, two dimensional gel electrophoresis of hVDR demonstrated several
      isoelectric forms of the receptor, suggesting that it is subject to multiple
      phosphorylation events. In vitro kinase assays confirmed that purified hVDR is an
      efficient substrate for protein kinases A and Cbeta, as well as casein kinase II.
      In vivo studies of the expressed receptor in intact cells, namely baculovirus
      vector infected Sf9 insect cells and transfected mammalian COS-7 cells,
      demonstrated that hVDR was phosphorylated in a hormone-enhanced fashion.
      Functional consequences of hVDR phosphorylation were suggested by the
      observations that: (i) potato acid phosphatase (PAP)-treated hVDR no longer
      interacted with the VDRE as either a homodimer or a heteromeric complex with RXR,
      and (ii) treatment of transfected COS-7 cells with a phosphatase inhibitor
      (okadaic acid) along with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) resulted in a
      synergistic enhancement of both hVDR phosphorylation and transactivation of a
      VDRE-linked reporter gene, compared to the effect of treatment with either agent
      alone. These studies point to a significant role for phosphorylation of VDR in
      regulating high-affinity VDR-RXR interactions with VDREs, and also in modulating
      1,25(OH)2D3-elicited transcriptional activation in target cells.

PMID- 11948700
TI  - Ex vivo expansion of apheresis-derived peripheral blood hematopoietic
      progenitors.
AB  - Because the administration of hematopoietic growth factors and the use of stem
      cell support often fails to alleviate the neutropenic phase induced by cytotoxic
      drugs, several investigators have attempted to expand ex vivo hematopoietic
      progenitors for clinical use. These attempts have clearly shown that the cultured
      cells are functional and can be safely administered to patients, but that the in
      vivo performance is disappointing and the concept as a whole is not yet
      clinically useful. The major reasons for these unsuccessful attempts are thought
      to be cumbersome cell fractionation techniques, contamination, prolonged
      incubation, and the use of less than ideal cytokine combinations. In response, we
      have developed a simple procedure for ex vivo expansion of myeloid progenitor
      cells. In this assay, unfractionated mononuclear cells from apheresis donors are
      incubated in nonpyrogenic plastic bags for 7 days in the presence of culture
      medium either containing fetal calf serum or human plasma, granulocyte colony
      stimulating factor, and stem cell factor. We have demonstrated that under these
      conditions the number of colony-forming units (CFU) granulocyte-macrophage (CFU
      GM) and of CFU-granulocyte-macrophage-erythroid-megakaryocyte (CFU-GEMM)
      increased 7- and 9-fold, respectively, by day 7 and the number of burst-forming
      units-erythroid (BFU-E) increased 2.7-fold by day 5 of culture. Significant
      increases in the numbers of cells expressing CD34+, CD34+/CD38+, CD34+/CD33+,
      CD34+/CD15+, and CD34+/CD90+ and significant declines in the numbers of cells
      expressing CD34+/CD38- and CD19 surface antigens were also observed. The relative
      numbers of cells expressing T-cell markers and CD56 surface antigen did not
      change. By using different concentrations of various hematopoietic growth factor
      combinations, we can increase the number of mature and immature cells of
      different hematopoietic lineages.

PMID- 11948701
TI  - Comparison of CD34+ cell collection efficiency on the COBE Spectra and Fenwal CS
      3000 Plus.
AB  - Optimal collections of mobilized CD34+ cells are important in terms of both
      patient toxicity and cost. The factors that determine CD34+ collection efficiency
      (CD34eff) of cell separators have not been well studied. In addition, because
      several cell separators are available, the type of collection device may also be
      a significant variable. Previous studies comparing the Baxter-Fenwal CS3000 and
      the COBE Spectra have not yielded consistent conclusions. Therefore, we
      retrospectively analyzed the collection outcomes of 163 consecutive donors with a
      peripheral CD34+ cell concentration (pCD34) of > or =5 cells/microl on the first
      collection that had been harvested on one or the other device. The CS3000 was
      found to yield a significantly higher CD34eff (50% vs. 39%, P = 0.006). However,
      donors were not balanced for several prognostic factors, which may contribute to
      CD34eff including mobilization with G-CSF vs. chemotherapy+G-CSF, average flow
      rate, and total volume of peripheral blood processed. When appropriate variables
      were included in a stepwise multiple variable analysis, cell separator type
      emerged as a significant independent predictive factor for CD34eff (P = 0.018).
      Our data indicates that the CS3000 will, on average, show a higher absolute CDeff
      of 8%. Furthermore, since the two devices differ in mechanism, prognostic factors
      may also differ. Comparisons suggest that peripheral blood WBC and hematocrit may
      be more important predictors for the CS3000.

PMID- 11948702
TI  - Altering interface detector positioning in combination with prestorage filtration
      to achieve a better quality of single donor platelet concentrates using the CS
      3000 Plus blood separator.
AB  - The interface detector (ID) is an optical density sensor that affects the quality
      of single donor platelet collection using the CS 3000 Plus blood separator. The
      purpose of this study was to evaluate the effect of altering ID position on
      platelet yields and the contamination of leukocytes (WBC) in platelet
      concentrates (PCs). Dual-needle apheresis procedures (n = 93) were performed
      using an A35 collection chamber. Plateletpheresis products were separated
      according to interface detector offset (IDO) positioning into four groups: A: IDO
      = 6 (n = 33), B: IDO = 10 (n = 28), C: IDO = 12 (n = 18), D: IDO = 18 (n = 14).
      For 32% of the collections, the closed system apheresis kit with integral
      Sepacell filter (Baxter) was used and 33% of them were leukodepleted using the
      LRP-6 (PALL) filter. Our results showed that: (1) Although the mean blood volume
      and the time of apheresis were significantly higher, the mean platelet (PLT)
      yields were significantly lower in PCs of group A as compared to all other groups
      (P < 0.0001). (2) The mean WBC content was significantly higher in PCs of group D
      as compared to all other groups (P < 0.0001). (3) With the LRP-6 filter, a
      significantly higher WBC reduction as well as PLT loss in PCs was observed as
      compared to Sepacell leukapheresis filter. A higher PLT loss was observed with
      both filters when leukoreduction was performed within the first 6 hours as
      compared to 24 hours after the procedure. Conclusively, an IDO setting of 10 or
      12 results in better platelet yields in PCs without increasing the WBC
      contamination. An IDO positioning of 18 or higher must be avoided or should be
      always combined with PCs leukodepletion. Finally, the best timing for
      leukoreduction is 24 hours after the plateletpheresis.

PMID- 11948703
TI  - Characteristics of photopheresis treatments for the management of rejection in
      heart and lung transplant recipients.
AB  - Photopheresis has been used in the management of rejection of heart and/or lung
      transplants. Although its mechanism of action remains unknown, irradiated T
      helper cell-induced immunosuppression is the main theory. Since transplant
      recipients are often lymphopenic and lymphocytes are the target cells in
      phototherapy, we performed this study to determine which factors affect the
      cellular yield to undergo irradiation. We reviewed the records of all
      photophereses performed in our institution between July 1998 and April 2000 using
      the UVAR (first generation) or XTS (second generation) instruments (Therakos,
      Exton, PA). Our data included patient's blood volume, absolute lymphocyte count
      and hematocrit, catheter type, flow rate of collection cycles and centrifuge bowl
      size, as well as volume, hematocrit, and lymphocyte count of the cell suspension.
      With a mixed model multivariate analysis we sought to determine which variables
      predicted the lymphocyte yield. A total of 406 procedures in 25 adult patients
      was analyzed. There was no significant difference between the lymphocyte yield
      among the procedures performed with the first- and the second-generation
      instruments. The patient's absolute lymphocyte count was the only parameter,
      which positively correlated with the total number of lymphocytes collected for
      irradiation (P < 0.0001). Indeed, based on the mixed model, the total number of
      lymphocytes for irradiation can be predicted from the pre-procedure lymphocyte
      count. Additional studies are necessary to correlate the number of treated cells
      with patient outcome.

PMID- 11948704
TI  - Hemodynamic study of serial double-filtration plasmapheresis.
AB  - Although hypotension is a potential complication for all procedures involving
      extracorporeal circulation, including plasmapheresis, the effects of serial
      double-filtration plasmapheresis (DFP) on hemodynamic status have rarely been
      reported. Blood pressure (BP) and pulse rate (PR) were prospectively monitored at
      30-minute intervals (baseline, M30, M60, M90, and Ml20) during procedures for 20
      myasthenia gravis patients who underwent one course of five consecutive DFP
      treatments on alternate days, with hemodynamic parameters recorded and analyzed
      for all sessions. To evaluate the hemodynamic influence of protein loss resulting
      from serial DFP treatment, additional analysis of serum protein levels including
      albumin and globulin was conducted before and after the entire course of
      treatment. Longitudinal analysis on the systolic BP (SBP) changes over five
      sessions revealed that the SBP at baseline and at M30 dropped significantly
      during the third and fourth sessions, in comparison to the first (P < 0.05). By
      contrast, SBP at M120 rose significantly (P < 0.05) after the second session of
      treatment. A similar trend was revealed for the diastolic BP (DBP) with a
      significant fall recorded at baseline and at M30 for the fourth session. The PR
      did not differ significantly during consecutive DFP treatments. Globulin removal
      rates were correlated significantly with falls in SBP (r(2) = 0.250, P = 0.048)
      and DBP (r(2) = 0.405, P = 0.008). However, analogous albumin removal rate was
      not correlated with these hemodynamic parameters. In conclusion, our results
      confirm that hypoproteinemia is an important factor for contributing to unstable
      hemodynamics during serial DFP.

PMID- 11948705
TI  - The effects of three different LDL-apheresis methods on the plasma concentrations
      of E-selectin, VCAM-1, and ICAM-1.
AB  - Plasma concentrations of cellular adhesion molecules are associated with
      atherosclerotic diseases and major cardiovascular risk factors. It was shown that
      LDL-apheresis with dextran sulfate lowers the levels of E-selectin and ICAM-1 in
      patients with familial hypercholesterolemia. The effects of different LDL
      apheresis methods have not been studied yet. Cholesterol, triglycerides, LDL
      cholesterol, HDL cholesterol, fibrinogen, and the adhesion molecules E-selectin,
      VCAM-1, and ICAM-1 were measured in 20 patients with coronary heart disease and
      severe hyperlipoproteinemia immediately before and after regular LDL-apheresis.
      Treatment was performed by different apheresis methods (direct absorption, DA, n
      = 6; dextran sulfate adsorption, DS, n = 7; heparin precipitation, HP, n = 7).
      Rebound data of adhesion molecule levels were obtained from 2 patients of each
      group. Lipids were reduced similarly in all groups. The concentrations of all
      adhesion molecules were lowered during apheresis. The reduction of E-selectin (
      31 +/- 7 vs. -6 +/- 5 and -6 +/- 5%, respectively, P < 0.001) was most prominent
      in the patients treated by heparin precipitation. Depending on the method of LDL
      apheresis, the concentrations of VCAM-1 and E-selectin in the outlets of the LDL
      apheresis columns were significantly lower compared to the concentration in the
      inlets. Plasma concentrations of adhesion molecules increased to their pre
      apheresis values within 2 to 4 days following LDL-apheresis. The reductions of
      adhesion molecule levels observed during LDL-apheresis are at least partly due to
      adsorption to the LDL-apheresis column. The extent of absorption depends on the
      principle of extracorporeal LDL elimination.

PMID- 11948706
TI  - Serum hyperviscosity syndrome responding to therapeutic plasmapheresis in a
      patient with primary Sjogren's syndrome.
AB  - Hyperviscosity syndrome is a disorder first described in patients with
      Waldenstrom's macroglobulinemia and is not commonly seen in rheumatic diseases.
      Its association with Sjogren's syndrome is very rare and it has been reported in
      very few patients. We report the case of a patient with primary Sjogren's
      syndrome presenting as hyperviscosity syndrome who was successfully treated with
      therapeutic plasma exchange.

PMID- 11948708
TI  - RE: Therapeutic plasma exchange: a paired comparison of Fresenius AS104 vs. COBE
      Spectra.

PMID- 11948707
TI  - Discontinuous-flow plasmapheresis and patent foramen ovale: a possible cause of
      paradoxical embolism.
AB  - A 68-year-old woman was admitted for a subacute polyradiculoneuropathy and
      submitted to PE. A central right jugular venous access was placed after the third
      PE procedure due to a failing peripheral blood access. During the fourth PE,
      performed with a discontinuous-flow system (continuous-flow used for 3
      procedures), she developed multiple embolic ischemic lesions in the left middle
      cerebral artery (MCA) territory. A thorough cerebrovascular screening showed only
      a patent foramen ovale (PFO). In our case, a possible increase of the right
      atrium blood pressure induced by the positive flux of the discontinuous-flow PE
      could have been responsible for a paradoxical embolism through the PFO. Plasma
      exchange (PE) is used in several neurologic disorders. It is commonly thought to
      be a relatively safe procedure. However, a number of adverse events may occur:
      paradoxical embolism has not been reported to occur.

PMID- 11948709
TI  - Crossing the line.

PMID- 11948710
TI  - Comparative study of pressure-flow parameters.
AB  - Methods for quantification of bladder outlet obstruction (BOO) are still
      controversial. Parameters such as detrusor opening pressure (p(det.open)),
      maximum detrusor pressure (p(det.max)), minimum voiding pressure
      (p(det.min.void)), and detrusor pressure at maximum flow rate (P(det.Qmax))
      separate obstructed from nonobstructed patients to some extent, but two
      nomograms, the Abrams-Griffiths nomogram and the linearized passive urethral
      resistance relation (LinPURR), are more accepted for this purpose, along with the
      urethral resistance algorithm. In this retrospective, methodologic study, we
      evaluated the properties of these parameters with regard to test-retest
      reproducibility and ability to detect a moderate (pharmacologic) and a pronounced
      (surgical) relief of bladder outlet obstruction. We studied the pressure-flow
      charts of 42 patients who underwent 24 weeks of androgen suppressive therapy, 42
      corresponding patients who received placebo, and 30 patients who had prostate
      surgery. The patients performed repeat void pressure-flow examinations before and
      after treatment or placebo. The various parameters were compared. Among the
      bladder pressure parameters, P(det.Qmax) seemed to have some advantages,
      supporting the belief that it is the most relevant detrusor pressure parameter to
      include in nomograms to quantify BOO. In assessment of a large decrease in
      urethral resistance, such as after TURp, resistance parameters that are based on
      maximum flow rate as well as detrusor pressure are preferable.

PMID- 11948711
TI  - Assessment of the intrinsic urethral sphincter component function in
      postprostatectomy urinary incontinence.
AB  - Postprostatectomy incontinence remains a disabling condition. Sphincter injury,
      detrusor instability, and decreased bladder compliance have been previously
      reported as major factors. The aim of this study was to evaluate the urethral
      sphincter intrinsic component, which may provide passive continence. A urodynamic
      evaluation was performed in 20 patients undergoing a radical retropubic
      prostatectomy in the preoperative period and 3 months after surgery. Patients
      with disabled urinary incontinence underwent a new urodynamic evaluation 6 months
      later. The urethral pressure profile was measured just before, then 10, 20, and
      30 minutes after the injection of 0.5 mg/kg moxisylyte chlorhydrate, an alpha
      adrenergic blocker. Three different pressure components were defined in urethral
      sphincter capacity: baseline, adrenergic, and voluntary. A postoperative
      intrinsic urethral sphincter pressure component was found in 17 patients and its
      value was under 6 cm H(2)O in five cases of severe incontinence. No significant
      difference was observed for these patients on urethral profile components 6
      months later. In contrast, in cases of significant intrinsic component value, no
      incontinence was observed in most patients. Passive continence after radical
      prostatectomy should be a matter of concern and may also explain paradoxical
      incontinence, despite high voluntary urethral pressure obtained after
      reeducation. A follow-up evaluation of the intrinsic sphincter component is
      suggested, by using an alpha receptor blockage test during urodynamic studies in
      the management of patients with postprostatectomy incontinence.

PMID- 11948712
TI  - Identifying cut-off scores with neural networks for interpretation of the
      incontinence impact questionnaire.
AB  - We propose to determine cut-off scores for the Incontinence Impact Questionnaire
      (IIQ) based on the neural network (NN) approach. These cut-off scores should
      discriminate between patients having poor, moderate, or good quality of life
      (QoL) secondary to their incontinence problems. Data from two prospectively
      completed QoL questionnaires, the IIQ (n = 237) and the MOS 36-Item Short-Form
      Health Survey (SF-36) (n = 237), were analyzed using NN and conventional
      statistical tools. Kohonen networks identified three distinct clusters of IIQ
      scores. The three clusters represent the full spectrum of possible scores on the
      IIQ. We interpreted these clusters as reflecting good, moderate, and poor QoL. We
      estimated that a score of less than 50 on the IIQ would be representative of good
      QoL, between 50 and 70 would be moderate QoL, and greater than 70 would be
      indicative of poor QoL. Validation with the SF-36 data confirmed these
      categories. The present study demonstrated that the NN approach is opening new
      areas in the interpretation and clinical usefulness of QoL questionnaires. NN
      allowed the identification of three levels of QoL and should be useful in
      clinical decision making.

PMID- 11948713
TI  - Voiding and incontinence frequencies: variability of diary data and required
      diary length.
AB  - Frequencies of voiding and urinary incontinence are commonly measured by a
      patient's recall or a diary. The recommended diary length varies from 1 to 14
      days, with 7 days apparently being most common. To examine the statistical
      precision of these different modalities, we analyzed recall data and diary data
      of 74 patients with urinary frequency, incontinence, or both. Recall data on
      voiding and incontinence frequency were systematically higher and more variable
      than diary data. Longer diary length provided less variable diary data. The
      confidence interval of diary data was calculated by applying the normal
      distribution to daytime voiding frequency and the Poisson distribution to daytime
      incontinence frequency. For daytime voiding frequency, the 95% confidence
      interval was estimated to be (x - 2.65, x + 2.65) (x - 1.53, x + 1.53) (x - 1, x
      + 1), where x is the 1-day, 3-day, and 7-day diary mean, respectively. For
      daytime incontinence frequency, the confidence interval depended on both the
      diary length and the diary mean. It was estimated to be (0, 6.39), (1.72, 4.28),
      (2.36, 3.64), by using a diary mean of 3 or 1-day, 7-day, and 28-day diaries,
      respectively. Also, it was estimated to be (0, 1.02), (1.72, 4.28), (7.66,
      12.34), when the 7-day diary mean was 0.5, 3, and 10, respectively. Studies with
      different samples of genuine stress incontinence (n = 37) and urge incontinence
      (n = 25) confirmed these results. In conclusion, we believe the 7-day diary is
      highly reliable for estimating voiding frequency and is a reasonable option for
      predicting incontinence episodes. However, the diary length should be extended in
      a patient with rarer events of incontinence, and it should be shortened for those
      who are incontinent more often or who are diagnosed with voiding frequency only.

PMID- 11948714
TI  - Bulbocavernosus muscle responses after suprapubic stimulation: analysis and
      measurement of suprapubic bulbocavernosus reflex latency.
AB  - Our objective was to describe pelvic floor responses with measurement of reflex
      latency after suprapubic mechanical stimulation. Twenty-one patients without
      neurological disease were studied. They were 14 women and seven men. The mean age
      was 51 (SD = 14.2). Motor responses were recorded with a needle electrode
      inserted in the left bulbocavernosus muscle. Stimulation was delivered with an
      electromechanical hammer, tapping directly on the suprapubic area. A polyphasic
      muscular response was always easily elicited in all patients. The man latency was
      67.5 milliseconds (SD = 14.7). The reproducibility between the first and second
      mechanical responses was good with no statistical difference (r=0.966;P =
      0.0001). In three patients who underwent cystometry, no rise in detrusor pressure
      was observed during mechanical stimulation of the suprapubic area. Our study
      clearly demonstrates a suprapubic bulbocavernosus reflex (SBR). Tapping the
      suprapubic area is a strong stimulus, reflexively mediated, used in the
      management of neurogenic bladder to determine a bladder contraction. However, the
      reflex consisting of pelvic floor muscle contraction after suprapubic stimulation
      was not specifically studied in humans. Many arguments can be put forth for a
      polysynaptic reflex (polyphasic response, habituation and short latency of the
      reflex, mean latency in the habitual values of R2 responses after electrical
      stimulation of the dorsal nerve of the penis). We hypothesize that the true
      stimulus is the stimulation of the bladder wall tensoreceptors, the integration
      level of the SBR is the sacral segments and the efferent limb the pudendal nerve,
      and afferent pathways could be conducted by pelvic nerve fibers. Competition
      between a preponderant (or exaggerated) SBR and a bladder contraction after
      suprapubic tapping may constitute an equivalent of detrusor-sphincter dyssynergia
      in some suprasacral bladders.

PMID- 11948715
TI  - Cerebral electrical response on urinary bladder filling: first experimental
      findings.
AB  - Micturition disorders in neurologic diseases are often combined with reduced
      bladder sensation. Bladder sensation is important to time the void appropriately
      and to prevent bladder overdistension. We attempted to evaluate cerebral evoked
      potentials by bladder distension to objectively determine bladder sensation. In
      six rabbits, cerebral evoked potentials were evaluated by averaging cerebral
      responses to bladder distension. We stimulated the bladder with a computerized
      air pump system, resulting in repeated filling and emptying of the bladder. The
      number of stimulations, stimulation intensity, and different
      electroencephalograph electrode positions (both mastoids and frontal) were
      investigated. In all rabbits, cerebral evoked potentials were observed after 500
      stimulations when stimulation pressure exceeded a certain threshold. Optimum
      response was observed after 1,000 stimulations. The latency of response of the
      frontal electrode position was observed after the mastoidal response with a
      significant delay of approximately 0.8 seconds. The latencies were significantly
      different when using different stimulation intensities. At lower intensity (mean
      pressure, 16.6 mm Hg), the response was observed after 4.531 +/- 0.909 seconds.
      At higher intensity (mean pressure, 19.0 mm Hg), cerebral response was observed
      after a latency of 3.971 +/- 0.735 seconds. We conclude that recording of
      cerebral evoked potentials by bladder distension is possible, resulting in an
      objective evaluation of afferent pathways from the bladder. In combination with
      subjective perception of bladder fullness, this finding may be a conceivable
      basis for a biofeedback training program to recover bladder sensation in patients
      with reduced bladder sensation.

PMID- 11948716
TI  - Role of supraspinal serotonin receptors for micturition in normal conscious rats.
AB  - Serotonin (5-HT) receptors are widely distributed in the central nervous system,
      including several areas involved in the control of micturition reflex pathways.
      However, the roles of the different subtypes of 5-HT receptors are not well
      known. We studied in normal, conscious rats, the effects on the cystometrogram of
      intracerebroventricular (i.c.v.) administration of 5-HT, 8-hydroxy-2-(di-N
      propylaminotetralin) (8-OH-DPAT; agonist at 5-HT(1A) receptors), alpha-methyl-5
      hydroxytryptamine maleate (agonist at 5-HT(2) receptors), 2-methyl-5
      hydroxytryptamine hydrochloride (agonist at 5-HT(3) receptors), and 1-(4-amino-5
      chloro-2methoxyphenyl)-3-(1-n-butyl-4piperidinyl)-1-propanone hydrochloride
      (RS67506; agonist at 5-HT(4) receptors). Female Sprague-Dawley rats, weighing
      approximately 230 g, were used. A polyethylene catheter was inserted into the
      bladder through the dome for cystometric investigations. For administration of
      drugs, a catheter was implanted into the right cerebral ventricle. Three days
      after implantation of the bladder catheter, continuous cystometry was performed.
      Administration of 5-HT (6 nmol/kg i.c.v.), 8-OH-DPAT (6 nmol/kg), alpha-methyl-5
      hydroxytryptamine maleate (6 nmol/kg), or RS67506 hydrochloride (6 nmol/kg)
      significantly (P < 0.05) increased micturition pressure and decreased bladder
      capacity and micturition volume. The effects increased in a dose-dependent manner
      (18, 60 nmol/kg). Intracerebroventricular administration of 2-methyl-5
      hydroxytryptamine hydrochloride (60 nmol/kg) caused no change in the cystometric
      parameters. The results suggest that in normal conscious rats, at the supraspinal
      level, 5-HT (via 5-HT(1A), 5-HT(2), and 5-HT(4) receptors) can enhance the
      micturition reflex induced by bladder filling. Whether this means that 5-HT(1A),
      5-HT(2), and 5-HT(4) receptors can be targets for drugs meant for treatment of
      bladder hyperactivity, should be explored.

PMID- 11948717
TI  - Partial unilateral ureteral obstruction in rats.
AB  - This review comprises an overview of the current knowledge on experimental
      partial unilateral ureteral obstruction (PUUO) and a summary of our latest
      original experimental PUUO studies in rats. Neonatal PUUO is the type of
      obstruction that is most often encountered in pediatric clinical practice.
      However, the pathogenesis of PUUO is still incompletely understood. Most of our
      knowledge on PUUO has been derived from experimental studies in a variety of
      animal models. Although progress has been made, the natural history of congenital
      hydronephrosis is still incompletely described. The effects on kidney functions
      of long-term urinary tract obstruction, especially PUUO, have been less
      intensively studied. Recently, we created models with mild and severe PUUO in
      young rats by embedding the upper one fourth or the upper two thirds of the left
      ureter into the psoas muscle, respectively. Thereafter, the technique was used to
      create mild and severe PUUO in newborn rats and magnetic resonance imaging
      studies showed that both mild and severe obstruction caused a time-dependent
      decrease in renal blood flow. Compensatory increase in total kidney volume and
      renal vein blood flow in contralateral non-obstructed kidneys was not detectable
      when functional deterioration in the partially obstructed kidneys was present.
      Finally, we investigated the dynamic changes in renal relative signal intensity
      (RSI) of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) using magnetic
      resonance imaging in rats with partial, complete unilateral ureteral obstruction
      and sham-operated controls. The results showed that changes in Gd-DTPA RSI are
      compatible with the known physiological and anatomical changes in kidneys in
      response to ureteral obstruction and useful for distinguishing an obstructed from
      a non-obstructed collecting system and also for differentiating a partially
      obstructed from a completely obstructed collecting system.

PMID- 11948718
TI  - Modification of ureteral motility and promotion of urine flow around an
      intraureteral obstruction by CL-316243, phenylephrine, and furosemide in dogs.
AB  - The aim of this study was to evaluate the effects of a beta3-adrenoceptor (AR)
      agonist (CL-316243), an alpha1-AR agonist (phenylephrine), and a loop diuretic
      (furosemide) on the spontaneous rhythmic contractions of the isolated canine
      ureter and on an acute ureteral obstruction produced by inflation of a balloon
      catheter in anesthetized dogs. In the isolated ureter, CL-316243 concentration
      dependently reduced both the amplitude and frequency of the rhythmic contractions
      (pD(2): 7.19 +/- 0.33), whereas phenylephrine significantly enhanced both
      variables (pD(2): 5.26 +/- 0.09) and furosemide reduced them only slightly. In
      the acute ureteral obstruction model, the intraureteral pressure (IUP) gradually
      rose to reach a plateau of 58.9 mm Hg after inflation of a balloon catheter
      within the lower ureter. Intravenous administration of CL-316243 (0.3 microg/kg)
      significantly reduced the elevated IUP and the resumed urine flow (UF), leading
      to a sustained reduction in the IUP. In contrast, the IUP continued to increase
      above the plateau level for 10 minutes after phenylephrine administration (10
      microg/kg) and for 30 minutes after furosemide administration (1,000 microg/kg).
      In the phenylephrine group, the UF resumed when the IUP reached 75.8 mm Hg, and
      thereafter the IUP gradually decreased in parallel with the increase in the UF.
      From these results, we conclude that in dogs, CL-316243 reduces the IUP by
      allowing the UF to resume as a result of a relaxation of ureter at the
      obstruction site, whereas with phenylephrine, the reduction in the IUP is
      secondary to a resumption in the UF resulting from an induced contraction of
      ureter that causes an increase in hydrostatic pressure above the obstruction
      site.

PMID- 11948719
TI  - Standardisation of urethral pressure measurement: report from the Standardisation
      Sub-Committee of the International Continence Society.

PMID- 11948720
TI  - Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow
      studies.
AB  - This is the first report of the International Continence Society (ICS) on the
      development of comprehensive guidelines for Good Urodynamic Practice for the
      measurement, quality control, and documentation of urodynamic investigations in
      both clinical and research environments. This report focuses on the most common
      urodynamics examinations; uroflowmetry, pressure recording during filling
      cystometry, and combined pressure-flow studies. The basic aspects of good
      urodynamic practice are discussed and a strategy for urodynamic measurement,
      equipment set-up and configuration, signal testing, plausibility controls,
      pattern recognition, and artifact correction are proposed. The problems of data
      analysis are mentioned only when they are relevant in the judgment of data
      quality. In general, recommendations are made for one specific technique. This
      does not imply that this technique is the only one possible. Rather, it means
      that this technique is well-established, and gives good results when used with
      the suggested standards of good urodynamic practice.

PMID- 11948721
TI  - In vivo mapping of the fast and slow diffusion tensors in human brain.
AB  - Recent studies have shown that the diffusional signal decay in human brain is non
      monoexponential and may be described in terms of compartmentalized water
      fractions. Diffusion tensor imaging (DTI), which provides information about
      tissue structure and orientation, typically uses b values up to 1000 s x mm(-2)
      so that the signal is dominated by the fast diffusing fraction. In this study b
      factors up to 3500 s x mm(-2) are utilized, allowing the diffusion tensor
      properties of the more slowly diffusing fraction to be mapped for the first time.
      The mean diffusivity (MD) of the slow diffusion tensor was found to exhibit
      strong white/gray matter (WM/GM) contrast. Maps depicting the principal direction
      of the slow tensor indicated alignment with the fast tensor and the known
      orientation of the WM pathways.

PMID- 11948722
TI  - Proton T2 relaxation study of water, N-acetylaspartate, and creatine in human
      brain using Hahn and Carr-Purcell spin echoes at 4T and 7T.
AB  - Carr-Purcell and Hahn spin-echo (SE) measurements were used to estimate the
      apparent transverse relaxation time constant (T2) of water and metabolites in
      human brain at 4T and 7T. A significant reduction in the T2 values of proton
      resonances (water, N-acetylaspartate, and creatine/phosphocreatine) was observed
      with increasing magnetic field strength and was attributed mainly to increased
      dynamic dephasing due to increased local susceptibility gradients. At high field,
      signal loss resulting from T2 decay can be substantially reduced using a Carr
      Purcell-type SE sequence.

PMID- 11948723
TI  - Imaging spin probe distribution in the tumor of a living mouse with 250 MHz EPR:
      correlation with BOLD MRI.
AB  - Electron paramagnetic resonance imaging (EPRI) promises to provide new insights
      into the physiology of tissues in health and disease. Understanding the in vivo
      imaging capability of this new modality requires comparison with other
      physiologically responsive techniques. Here, an initial comparison between 2D EPR
      spatial imaging of a narrow single line injectable paramagnetic trityl spin probe
      and 2D slice-selected carbogen subtraction BOLD MRI is presented. The images were
      obtained from the same FSa fibrosarcoma grown in the leg of a C3H mouse. This
      tumor was unusual in comparison with others imaged with subtraction BOLD MRI
      because of its peripheral distribution of intensity. The spatial distribution of
      the EPR spin probe showed the same peripheral distribution. The pixel resolutions
      of these images are comparable. These images provide an early in vivo comparison
      of EPRI with a well-established imaging modality. The comparison validates the in
      vivo distribution of spin probe as imaged with EPRI, and provides a proof of
      principle for the comparison of BOLD and EPRI.

PMID- 11948724
TI  - Paramagnetic lanthanide(III) complexes as pH-sensitive chemical exchange
      saturation transfer (CEST) contrast agents for MRI applications.
AB  - The recently introduced new class of contrast agents (CAs) based on chemical
      exchange saturation transfer (CEST) may have a huge potential for the development
      of novel applications in the field of MRI. In this work we explored the CEST
      properties of a series of Lanthanide(III) complexes (Ln = Eu, Dy, Ho, Er, Tm, Yb)
      with the macrocyclic DOTAM-Gly ligand, which is the tetraglycineamide derivative
      of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). These
      complexes possess two pools of exchangeable protons represented by the
      coordinated water and the amide protons. Yb-DOTAM-Gly displays the most
      interesting CEST properties when its amide N-H resonance (16 ppm upfield H2O
      signal) is irradiated. Up to 70% suppression of the water signal is obtained at
      pH 8. As the exchange rate of amide protons is base-catalyzed, Yb-DOTAM-Gly
      results to be an efficient pH-responsive probe in the 5.5-8.1 pH range. Moreover,
      a ratiometric method has been set up in order to remove the dependence of the
      observed pH responsiveness from the absolute concentration of the paramagnetic
      agent. In fact, the use of a mixture of Eu-DOTAM-Gly and Yb-DOTAM-Gly, whose
      exchangeable proton pools are represented by the coordinated water (ca. 40 ppm
      downfield H2O signal at 312K) and amide protons, respectively, produces a pH
      dependent CEST effect which is the function of the concentration ratio of the two
      complexes.

PMID- 11948725
TI  - Estimation of local aortic elastic properties with MRI.
AB  - Aortic compliance and pulse wave velocity (PWV) are important determiners of
      heart load, and are clinically useful indices of cardiovascular risk. Most direct
      methods to derive them require invasive pressure measurement. In this work a
      noninvasive technique to evaluate aortic compliance and PWV using MRI is
      proposed. MRI magnitude and phase images to measure area and flow in the
      ascending aorta were acquired in a group of 13 young healthy subjects. Assuming
      that the early systolic part of the wave was unidirectional and reflectionless,
      PWV was determined as the ratio between flow and area variations at early
      systole. Our results were compared to pulse wave velocities derived from a direct
      transit time, and to one using ascending aortic area and peripheral brachial
      pulse pressure. The new method proved to be accurate and in good agreement with
      the transit time method, as well as with previously published results.

PMID- 11948726
TI  - Multishot EPI-SSFP in the heart.
AB  - Refocused steady-state free precession (SSFP), or fast imaging with steady
      precession (FISP or TrueFISP), has recently proven valuable for cardiac imaging
      because of its high signal-to-noise ratio (SNR) and excellent blood-myocardium
      contrast. In this study, various implementations of multiecho SSFP or EPI-SSFP
      for imaging in the heart are presented. EPI-SSFP has higher scan-time efficiency
      than single-echo SSFP, as two or more phase-encode lines are acquired per
      repetition time (TR) at the cost of a modest increase in TR. To minimize TR, a
      noninterleaved phase-encode order in conjunction with a phased-array ghost
      elimination (PAGE) technique was employed, removing the need for echo time
      shifting (ETS). The multishot implementation of EPI-SSFP was used to decrease the
      breath-hold duration for cine acquisitions or to increase the temporal or spatial
      resolution for a fixed breath-hold duration. The greatest gain in efficiency was
      obtained with the use of a three-echo acquisition. Image quality for cardiac cine
      applications using multishot EPI-SSFP was comparable to that of single-echo SSFP
      in terms of blood-myocardium contrast and contrast-to-noise ratio (CNR). The PAGE
      method considerably reduced flow artifacts due to both the inherent ghost
      suppression and the concomitant reduction in phase-encode blip size. The
      increased TR of multishot EPI-SSFP led to a reduced specific absorption rate
      (SAR) for a fixed RF flip angle, and allowed the use of a larger flip angle
      without increasing the SAR above the FDA-approved limits.

PMID- 11948727
TI  - Phase contrast MRI of myocardial 3D strain by encoding contiguous slices in a
      single shot.
AB  - Quantitative measurements of inherently three-dimensional (3D) cardiac strain and
      strain rate require 3D data; MRI provides uniquely high sensitivity to material
      strain by combining phase contrast with single-shot acquisition methods, such as
      echo-planar imaging (EPI). Previous MRI methods applied to 3D strain used
      multiple two-dimensional (2D) acquisitions and suffered loss of sensitivity due
      to magnification within the strain calculation of physiologic noise related to
      cardiac beat-to-beat variability. In the present work, each single-shot
      acquisition generates 3D image data by acquiring two contiguous 2D Fourier
      transform (FT) images in a single echo train of an EPI readout. Although strain
      encoding divides across multiple EPI shots, each strain component is computed
      only within single-shot data, avoiding noise magnification. Strain tensor maps
      are displayed using iconic 3D graphics or a simple color code of tensor shape. In
      a deforming gel phantom, gradient-recalled echo (GRE) MRI movies of 3D strain
      rates match expected strain fields. In normal human subjects, 3D strain rate
      tensor movies of heart and brain comprising seven slices in each of seven cardiac
      phases were completed in 56 heartbeats. Stimulated echo (STE) MRI of net systolic
      3D strain was also demonstrated. Two-slices-in-one-shot spatial encoding permits
      a complete quantitative survey of ventricular 3D strain in under a minute, with
      routine patient supervision and turnkey image processing.

PMID- 11948728
TI  - Detection and elimination of motion artifacts by regeneration of k-space.
AB  - A method has been developed using techniques from partially parallel imaging
      (PPI) to detect localized inconsistencies in k-space that are caused by certain
      types of motion. The inconsistent data are discarded and consistent data
      regenerated from the remaining data using PPI techniques. The price is a small
      decrease in signal-to-noise ratio (SNR) and additional postprocessing. An
      iterative scheme is presented which does not require separately acquired coil
      sensitivity information for the PPI reconstructions. This method has been found
      to reduce artifact levels in phantom and in vivo test studies.

PMID- 11948729
TI  - k-space filtering in 2D gradient-echo breath-hold hyperpolarized 3He MRI: spatial
      resolution and signal-to-noise ratio considerations.
AB  - In this work some of the factors that can influence the signal-to-noise ratio
      (SNR) and spatial resolution in MR images of inhaled hyperpolarized gases are
      systematically addressed. In particular, the effects of RF depletion of
      longitudinal polarization and image gradient diffusion dephasing were assessed in
      terms of their contribution to a k-space filter. By means of theoretical
      simulations and a novel method of experimental validation using a variable
      transverse magnetization of the 1H signal, systematic quantitative and
      qualitative investigations of the effects of k-space filtering intrinsic to
      imaging of hyperpolarized gas were made. A 2D gradient-echo image is considered
      for a range of flip angles with centric, sequential, and half-Fourier Cartesian
      phase-encoding strategies, and the results are assessed in terms of SNR and
      spatial resolution in the reconstructed images. Centric phase encoding was found
      to give the best SNR at higher flip angles, with a trade-off in spatial
      resolution compared to sequential phase encoding. A half-Fourier approach
      potentially offers increased SNR through the use of higher flip angles without
      compromising the spatial resolution, which is comparable to that achieved with
      sequential encoding.

PMID- 11948730
TI  - Fast maximum intensity projection algorithm using shear warp factorization and
      reduced resampling.
AB  - Maximal intensity projection (MIP) is routinely used to view MRA and other
      volumetric angiographic data. The straightforward implementation of MIP is ray
      casting that traces a volumetric data set in a computationally expensive manner.
      This article reports a fast MIP algorithm using shear warp factorization and
      reduced resampling that drastically reduced the redundancy in the computations
      for projection, thereby speeding up MIP by more than 10 times.

PMID- 11948731
TI  - Limitations and requirements of diffusion tensor fiber tracking: an assessment
      using simulations.
AB  - Diffusion tensor fiber tracking potentially can give information about in vivo
      brain connectivity. However, this technique is difficult to validate due to the
      lack of a gold standard. Fiber tracking reliability will depend on the quality of
      the data and on the robustness of the algorithms used. Information about the
      effects of various anatomical and image acquisition parameters on fiber tracking
      reliability may be used in the design of imaging sequences and of tracking
      algorithms. In this study, tracking was performed on two different simulated
      models to study the effects on tracking quality of SNR, anisotropy, curvature,
      fiber cross-section, background anisotropy, step size, and interpolation.
      Tracking was also performed on volunteer data to assess the relevance of the
      simulations to real data. Our results show that, in general, tracking with high
      SNR and high anisotropy using interpolation and a low step size gives the most
      reliable results. Partial volume effects are shown to have a detrimental effect
      when the background is anisotropic and when tracking narrow fibers. The results
      derived from real data show similar trends and thus support the findings of the
      simulations. These simulations may therefore help to determine which structures
      can be tracked for a given image quality.

PMID- 11948732
TI  - Quantitative analysis of adiabatic fast passage for steady laminar and turbulent
      flows.
AB  - Adiabatic fast passage (AFP) is used in noninvasive quantitative perfusion
      experiments to invert (or label) arterial spins. Continuous arterial spin
      labeling (CASL) experiments conducted in vivo often assume the inversion
      efficiency based on the labeling field and steady flow conditions, without direct
      verification. In practice, the labeling field used in CASL is often amplitude-
      and duty cycle-limited due to hardware or specific absorption rate constraints.
      In this study, the effects of the labeling field amplitude and duty cycle, and
      flow dynamics on the inversion efficiency of AFP were examined under steady flow
      conditions in a saline flow phantom. The experimental results were in general
      agreement with models based on Zhernovoi's theory except at high labeling field
      amplitudes, when the spin inversion times are at least half of the duration of
      the labeling pulse. The nonlinear relation observed between the inversion
      efficiency and the labeling duty cycle implies that the practice of linear
      derating the inversion efficiency with the labeling duty cycle may be prone to
      significant error. A secondary finding was that the T1 of the flowing fluid could
      be calculated based on the flow dynamics after varying the flow rate.

PMID- 11948733
TI  - MRI of muscular fat.
AB  - An MRI technique with high selectivity and sensitivity to the signal components
      in the chemical shift range of methylene and methyl protons of fatty acids has
      been developed for noninvasive assessment of muscular fat in vivo. A spoiled
      gradient-echo sequence with spatial-spectral excitation by six equidistant pulses
      with 2 degrees -(-9 degrees )-17 degrees -(-17 degrees )-9 degrees -(-2 degrees )
      and a multi-echo train (TE = 16, 36, 56, 76, 96, and 116 ms) allowed a series of
      images to be recorded with a receiver bandwidth of 78 Hz per pixel. SIs from
      phantoms with lipid contents between 0.1% and 100% were compared to those from
      pure water. Thirty healthy volunteers underwent fat-selective imaging of their
      lower leg, and parallel localized proton spectroscopy of the tibialis anterior
      and the soleus muscle by a single-voxel stimulated echo acquisition mode (STEAM)
      technique (TR = 2 s, TE = 10 ms, TM = 15 ms). Results show a high correlation (r
      = 0.91) between fat imaging and the spectroscopic approach in the soleus muscle,
      considering the percentage total fat content of musculature. The correlation
      coefficient was clearly lower (r = 0.55) in the tibialis anterior muscle due to
      signal contaminations from adjacent subcutaneous fat in the images, inhomogeneous
      fat distribution, and generally lower lipid content in this muscle. Applications
      of the new imaging technique showed marked intra- and interindividual variability
      in the spatial distribution of lipids in the musculature of the lower leg. No
      significant correlation of the muscular fat with the thickness of the
      subcutaneous fat layer was found. In addition, the body mass index does not
      appear to determine muscular fat content, except in very obese cases.

PMID- 11948734
TI  - Imaging the changes in renal T1 induced by the inhalation of pure oxygen: a
      feasibility study.
AB  - The effect of the inhalation of pure oxygen on the kidney was evaluated by
      measuring monoexponential T1 and T2* relaxation times in nine volunteers using a
      multiple-shot turbo spin echo and multiple echo gradient echo sequences,
      respectively. The T1 of the renal cortex decreased significantly when breathing
      pure oxygen as compared to normoxia (from 882 +/- 59 to 829 +/- 70 msec, P <
      0.05), while that of the renal medulla was unchanged. No significant changes were
      seen in the T2* of either compartment. Dynamic imaging using an inversion
      recovery sequence with an optimized inversion time typically produced signal
      changes of 20% in the renal cortex. Studies to assess if oxygen-induced changes
      in flow contributed to this effect showed that the flow contribution was not
      significant. Although longer inversion times (880 ms) produced optimal contrast,
      acceptable contrast was also obtained at shorter inversion times (450 msec) in
      the renal cortex, spleen, and lung, with the latter being of opposite polarity to
      the other two tissues, implying a shorter parenchymal T1 than previously reported
      in the literature. The results are consistent with oxygen acting as an
      intravascular contrast agent which induces a shortening of T1 in the arterial
      blood volume.

PMID- 11948735
TI  - Comparison of diffusion-weighted high-resolution CBF and spin-echo BOLD fMRI at
      9.4 T.
AB  - The quantification of blood oxygenation-level dependent (BOLD) functional MRI
      (fMRI) signals is closely related to cerebral blood flow (CBF) change; therefore,
      understanding the exact relationship between BOLD and CBF changes on a pixel-by
      pixel basis is fundamental. In this study, quantitative CBF changes induced by
      neural activity were used to quantify BOLD signal changes during somatosensory
      stimulation in alpha-chloralose-anesthetized rats. To examine the influence of
      fast-moving vascular spins in quantifying CBF, bipolar gradients were employed.
      Our data show no significant difference in relative CBF changes obtained with and
      without bipolar gradients. To compare BOLD and CBF signal changes induced by
      neural stimulation, a spin-echo (SE) sequence with long SE time of 40 ms at 9.4 T
      was used in conjunction with an arterial spin labeling technique. SE BOLD changes
      were quantitatively correlated to CBF changes on a pixel-by-pixel and animal-by
      animal basis. Thus, SE BOLD-based fMRI at high magnetic fields allows a
      quantitative comparison of functional brain activities across brain regions and
      subjects.

PMID- 11948736
TI  - In vivo 1H2O T2+ measurement in the human occipital lobe at 4T and 7T by Carr
      Purcell MRI: detection of microscopic susceptibility contrast.
AB  - A high-resolution spin-echo imaging method is presented (called CP-LASER) which
      exploits the spin refocusing capability of an adiabatic Carr-Purcell (CP) pulse
      sequence to measure apparent 1H2O transverse relaxation (T2+) and generate
      contrast based on microscopic tissue susceptibility. High-resolution CP-LASER
      images of the human occipital lobe were acquired at four different echo times
      from six subjects at 4T and eight subjects at 7T to investigate the effect of
      magnetic field strength (B(0)) and the CP interpulse time (tau(cp)) on T2+.
      Susceptibility contrast was identified and T2+ was quantified for long tau(cp)
      (>10 ms) and short tau(cp) (7 ms at 4T and 6 ms at 7T) in gray matter, white
      matter, and cerebral spinal fluid. The 1H2O relaxation rate constants (1/T2+) of
      gray and white matter each increased approximately linearly with field strength
      and T2+ was inversely related to tau(cp). The average T2+ value of gray matter
      was 19% and 9% smaller than that of white matter at 4T and 7T, respectively.
      These results are consistent with higher levels of compartmentalized ferritin and
      increased blood volume in gray matter compared to white matter in this region of
      the brain.

PMID- 11948737
TI  - MRI of insulitis in autoimmune diabetes.
AB  - Development of imaging techniques that would allow the mapping of immune cells in
      vivo could greatly aid our understanding of a number of inflammatory and
      autoimmune diseases. The current study focused on imaging of autoimmune
      destruction of the insulin-producing pancreatic beta-cells by cytotoxic
      lymphocytes, the cause of insulin-dependent diabetes mellitus (IDDM; Type 1
      diabetes). Using high-resolution MR microscopy and a conventional clinical MR
      imaging system, it was possible to visualize the infiltration of immune cells in
      the diabetic mouse pancreas. Mouse lymphocytes were visualized by magnetically
      labeling them with recently developed magnetic nanoparticles (CLIO-Tat). The
      results from this study could potentially lead to detection of immune
      infiltration during diabetes formation in vivo, which would be one of the
      earliest parameters of disease development.

PMID- 11948738
TI  - Recovery of function in cytoprotected cerebral cortex in rat stroke model
      assessed by functional MRI.
AB  - Functional recovery in cytoprotected somatosensory cortex in a rat stroke model
      was studied using functional MRI (fMRI). Calcium antagonist treatment
      (isradipine) following permanent middle cerebral artery occlusion (pMCAO) reduced
      the infarct volume by 33 +/- 9%. The somatosensory cortex representing the
      forepaws was spared from infarction; however, cerebral blood flow (CBF) was
      significantly reduced in this area 24 hr following pMCAO. Neural function was
      assessed at days 1, 2, 5, and 12 following pMCAO by fMRI using electrical
      stimulation of both forepaws. Vehicle-treated rats did not show fMRI responses in
      the infarcted somatosensory cortex throughout the study. Several of the
      isradipine-treated animals displayed functional recovery in the cytoprotected
      cortex at days 5 (3/5 rats) and 12 (5/10). Correlations with fMRI signals showed
      that normal T2 and ADC values in the respective brain areas are necessary, but
      not sufficient prerequisites for functionality. Recovery of neural function is
      associated with normalization of CBF in the cytoprotected brain area.

PMID- 11948739
TI  - Spatial/temporal correlation of BOLD and optical intrinsic signals in humans.
AB  - Comparing the BOLD signal with electrophysiological maps and other perfusion
      dependent signals, such as the optical intrinsic signal (OIS), within subjects
      should provide insight into the etiology of the BOLD signal. Tongue activations
      were compared in five human subjects using BOLD fMRI, 610-nm OIS, and the
      electrocortical stimulation map (ESM). Robust fMRI activations centered on the
      lateral inferior aspect of the central sulcus and extended into pre- and post
      central gyri, adjacent to ESM tongue loci. OIS and fMRI maps colocalized,
      although optical responses were spatially larger (P <.001 across multiple
      thresholds) and contained more gyral components. The timecourses of the fMRI and
      OIS signals were similar, appearing within 2.5 s and peaking 6-8 s after task
      onset. Although many processes contribute to increased 610-nm reflectance,
      optical spectroscopy and fluorescent dye imaging suggest that a significant part
      of this signal is due to a concomitant decrease in deoxyhemoglobin and increase
      in oxyhemoglobin concentrations. The spatial/temporal correlation of BOLD and the
      positive 610-nm response within subjects suggests that the two signals may share
      similar etiologies. The OIS/fMRI inconsistencies may be due to cell swelling and
      light-scattering contributions to OIS and fMRI sensitivity. This study also
      demonstrates that fMRI maps do not precisely colocalize with ESM, rather they
      emphasize changes in adjacent venous/sulcal structures.

PMID- 11948740
TI  - Simulation-based investigation of partially parallel imaging with a linear array
      at high accelerations.
AB  - Partially parallel imaging strategies such as SMASH, SENSE, and PILS rely on the
      sensitivity distribution of phased array RF coils to reduce MRI imaging time.
      Using an N-element phased array, these techniques allow maximum accelerations, L,
      such that L < or = N, with acceleration defined as the factor by which scan time
      is reduced in comparison to traditional, fully gradient encoded acquisitions. As
      N increases in modern MRI facilities or using special hardware extensions, its
      role as the primary limitation in partially parallel imaging will be reduced and
      other limiting factors will become dominant. Two such factors include available
      SNR and the variation of sensitivity distributions with imaging depth.
      Simulations have been conducted to evaluate the impact of slice depth and noise
      on partially parallel reconstructions for the case of a square linear array of
      overlapped elements that are parallel to the imaging plane. Results indicate that
      even when sensitivity distributions are exactly known, the linear surface array
      can only provide high accelerations over a limited imaging depth due to changing
      suitability of the sensitivity distributions for partially parallel
      reconstruction. This work emphasizes the importance of simulations for target
      based partially parallel array design.

PMID- 11948741
TI  - Quantification of myocardial blood flow and blood flow reserve in the presence of
      arterial dispersion: a simulation study.
AB  - Myocardial blood flow (MBF) can be quantified using dynamic T1-weighted MRI of
      diffusible tracers and a mathematical model of underlying vasculature.
      Quantification of MBF by means of T1- weighted MRI requires knowledge of the
      arterial input function (AIF). The AIF can be estimated from the left ventricular
      (LV) cavity. However, dispersion may occur between the LV and the tissue of
      interest because of the laminar blood flow profiles, branching of venules, and
      because of stenosis. To evaluate the influence of dispersion on the results of
      MBF quantification, a simulation study was performed. The dispersion was
      described as a convolution of the AIF with an exponential residue function.
      Synthetic tissue and AIF curves were analyzed and the derived parameters fit to
      the simulated parameters. The results show that an unaccounted dispersion may
      result in a systematic underestimation of MBF up to approximately 50%.
      Underestimation increases with increasing dispersion and with increasing MBF.
      Assuming equal dispersion at rest and during hyperemia, myocardial perfusion
      reserve (MPR) estimates are also susceptible to underestimation of approximately
      20%. An unaccounted dispersion therefore can lead to systematic underestimation
      of both blood flow and perfusion reserve.

PMID- 11948742
TI  - Solenoidal array coils.
AB  - New concepts are presented for inherent decoupling of multi-element solenoidal
      arrays. First, an uneven counter-rotational (UCR) coil is reported in which two
      counter-rotational sections are wound unevenly, resulting in a quasi-one-peak
      sensitivity profile with a null-B1 point. Adding a second solenoid element near
      the null-B1 point forms an inherently-decoupled solenoidal array. Unlike a
      sandwiched solenoidal array, an UCR solenoidal array allows for signal
      contribution at the center from both solenoid elements. Second, a double counter
      rotational (DCR) coil is presented in which two null-B1 points are formed by
      having one counter-rotational winding on each side of the coil. Two solenoidal
      elements can be added to form a solenoidal array. Finally, more solenoid elements
      can be added to the array provided that the added coil elements are DCR elements.
      These DCR coil elements can be used as building blocks for more complex
      solenoidal arrays. These concepts are illustrated using numerical simulations and
      tested using prototype coils.

PMID- 11948743
TI  - Gradient system providing continuously variable field characteristics.
AB  - Peripheral nerve stimulation limits the use of whole-body gradient systems
      capable of slew rates > 80 T/m/s and gradient strengths > 25 mT/m. The
      stimulation threshold depends mainly on the amplitude of the induced electric
      field in the patient's body, and thus can be influenced by changing the total
      magnetic flux of the gradient coil. A gradient system was built which allows
      continuous variation of the field characteristics in order to permit the use of
      full gradient performance without stimulation (slew rate 190-210 T/m/s, G(max) 32
      40 mT/m). The system consists of a modular six-channel gradient coil designed
      with a modified target field method, two three-channel amplifiers, and a six
      channel gradient controller. It is demonstrated that two coils on one gradient
      axis can be driven by two amplifiers in parallel, without significant changes in
      image quality. Scaling of the field properties and stimulation threshold
      according to the current polarity and ratio of both coil sets was verified in
      both phantom and volunteer studies.

PMID- 11948744
TI  - Human rectal adenocarcinoma: demonstration of 1H-MR spectra in vivo at 1.5 T.
AB  - This study was designed to determine whether 1H-MR spectra of locally advanced
      human rectal adenocarcinoma could be acquired in vivo at 1.5 T. Despite the
      relatively large size of these neoplasms, only six out of 21 tumors accommodated
      a voxel size of 8 cm3. This was due to air pockets within the tumor mass, which
      limited voxel positioning. Localized proton spectra were acquired at short (20
      ms) and long (135 ms) echo times (TEs) using a single-voxel technique. The most
      commonly detected metabolites were choline and lipid.

PMID- 11948745
TI  - Image-based EPI ghost correction using an algorithm based on projection onto
      convex sets (POCS).
AB  - This work describes the use of a method, based on the projection onto convex sets
      (POCS) algorithm, for reduction of the N/2 ghost in echo-planar imaging (EPI). In
      this method, ghosts outside the parent image are set to zero and a model k-space
      is obtained from the Fourier transform (FT) of the resulting image. The zeroth-
      and first-order phase corrections for each line of the original k-space are
      estimated by comparison with the corresponding line in the model k-space. To
      overcome problems of phase wrapping, the first-order phase corrections for the
      lines of the original k-space are estimated by registration with the
      corresponding lines in the model k-space. It is shown that applying these
      corrections will result in a reduction of the ghost, and that iterating the
      process will result in a convergence towards an image in which the ghost is
      minimized. The method is tested on spin-echo EPI data. The results show that the
      method is robust and remarkably effective, reducing the N/2 ghost to a level
      nearly comparable to that achieved with reference scans.

PMID- 11948746
TI  - Origin and minimization of residual motion-related artifacts in navigator
      corrected segmented diffusion-weighted EPI of the human brain.
AB  - Motion sensitivity in diffusion-weighted imaging (DWI) can be effectively
      suppressed using single-shot echo-planar imaging (EPI). However, segmented
      (multishot) EPI is often used to increase resolution and reduce spatial
      distortions, which in turn increases susceptibility to brain motion. The sources
      of these residual motion artifacts in navigator-echo-corrected segmented EPI
      images of the brain were investigated. The results indicate that the dominant
      source of these artifacts is cardiac pulsation with occasional involuntary
      movement of the subject. The relationship between the cardiac cycle and motion
      artifacts shows that optimum timing for the data acquisition is possible. In
      addition it is shown that the effects of involuntary motion can be removed by
      swapping k-space data between redundant datasets.

PMID- 11948748
TI  - Deep brain stimulation for movement disorders.

PMID- 11948747
TI  - Mohr diagram representation of anisotropic diffusion tensor in MRI.
AB  - With current approaches, it is difficult to visually comprehend the complete
      information contained in a diffusion tensor (DT) measured from a microscopically
      heterogeneous biological tissue. Therefore, in this work the Mohr diagram is
      introduced to graphically display the key aspects of DTs and to interpret the
      underlying anisotropy, both qualitatively and quantitatively. Specifically, the
      mathematical basis for the construction of the Mohr diagram from the elements of
      DTs is described, the merits of the approach are illustrated with examples of DTs
      reported for various biological tissues, and the results are discussed in the
      context of relating the diffusion anisotropy to the tissue structures.

PMID- 11948749
TI  - Surgery of the motor thalamus: problems with the present nomenclatures.
AB  - The literature on thalamic surgery is difficult to read because different
      nomenclatures are in use. Neurosurgeons mostly use the stereotactic atlas of
      Schaltenbrand with Hassler's nomenclature of the thalamus. Neuroanatomists use
      different nomenclatures for the primate thalamus. The cytoarchitectonic
      definition of nuclei is difficult in the motor thalamus, and it would be best to
      define the nuclei based on their subcortical afferents. However, tracing studies
      are not available in humans. Thus, human thalamic nomenclature is based entirely
      on cytoarchitectonic subdivisions and transfer of knowledge by analogy from
      monkey to man. Problems arise when trying to transfer the detailed knowledge from
      monkey to the human brain. By doing so, different authors have come to different
      conclusions concerning the subcortical afferents of Hassler's motor nuclei, which
      inevitably leads to confusion when attempting neurophysiological interpretations
      of the surgical data. The present review draws attention to the discrepancies and
      open questions in the literature. There is a need to better define the limits of
      the sensory and cerebellar afferent receiving thalamic nuclei as well as those of
      the cerebellar and pallidal afferent receiving territories in humans.

PMID- 11948750
TI  - Motor thalamic circuits in primates with emphasis on the area targeted in
      treatment of movement disorders.
AB  - The ventral region of the motor thalamus that receives cerebellar afferents has
      been and still is the target of stereotactic interventions for movement
      disorders. According to Hassler, this area includes ventro-oralis posterior (Vop)
      and ventral intermedius (Vim) nuclei, although some investigators believe that
      Vop is associated with the pallidothalamic pathway. We sought to correlate our
      experimental data on distribution of nigral, pallidal, and cerebellar afferents
      to the monkey thalamus with Hassler's motor thalamic parcelations. We concluded
      that Hassler's parcelations retained their value, although some adjustments were
      needed to relate them to the current neuroanatomic data; particularly, the
      cerebellothalamic zone that represents the monkey ventral lateral nucleus (VL)
      corresponds topographically to Hassler's Vop, Vim, and most of Voi. Electron
      microscopic tracing studies have shown very complex circuitry in this region of
      the monkey thalamus, as the cerebellar and cortical afferents innervating it are
      engaged in complex synapses with thalamocortical projection neurons, and this
      interaction is strongly modulated by local circuit neurons and the input from the
      reticular thalamic nucleus, which are both inhibitory and gamma-aminobutyric acid
      (GABA)ergic. Spinothalamic afferents also reach the VL, but this input is less
      studied in the monkey. The circuitry subserving the activity of thalamocortical
      projection neurons in the VL should be considered while interpreting the
      functional data obtained in stereotactic surgery.

PMID- 11948751
TI  - Functional anatomy of the basal ganglia.
AB  - Four organizational levels of the basal ganglia that could be particularly
      determinant in terms of functional properties are reviewed: (1) macroscopic
      anatomy, which is characterized by a dramatic decrease of cerebral tissue volume
      from the cerebral cortex to the deepest portions of the basal ganglia; (2)
      connectivity, which consists of both complex loops and a partition into three
      territories, sensorimotor, associative, and limbic (which process motor,
      cognitive, and emotional information, respectively); (3) neuronal morphology,
      characterized by a dramatic numeric and geometric convergence of striatal neurons
      onto pallidonigral neurons; and (4) dopaminergic innervation of the basal
      ganglia, which is organized as a dual system that is supposed to have opposite
      effects on the activity of the system. Current models of the basal ganglia are
      discussed.

PMID- 11948753
TI  - Pathophysiology of Parkinson's disease: from clinical neurology to basic
      neuroscience and back.
AB  - Parkinson's disease (PD) is characterized by motor and nonmotor (cognitive and
      limbic) deficits. The motor signs of PD include hypokinetic signs such as
      akinesia/bradykinesia, rigidity and loss of normal postural reflexes, and
      hyperkinetic signs such as tremor. Dopamine depletion in the striatum is the
      hallmark of PD and of its animal models, still the pathophysiology of the
      parkinsonian symptoms and especially of parkinsonian tremor are under debate. The
      most extreme hypotheses argue about peripheral versus central nervous system
      origin, intrinsic cellular oscillator versus network oscillators, and basal
      ganglia-based pathophysiology versus cerebellar-thalamic based pathophysiology.
      Recent studies support the view that parkinsonian symptoms are most likely due to
      abnormal synchronous oscillating neuronal activity within the basal ganglia.
      Peripheral factors do only play a minor role for the generation, maintenance, and
      modulation of PD tremor and other signs. The most likely candidates producing
      these neuronal oscillations are the weakly coupled neural networks of the basal
      ganglia-thalamo-cortical loops. However, the present evidence supports the view
      that the basal ganglia loops are influenced by other neuronal structures and
      systems and that the tuning of these loops by cerebello-thalamic mechanisms and
      by other modulator neurotransmitter systems entrain the abnormal synchronized
      oscillations. Neurosurgical procedures, such as lesions or high-frequency
      stimulation of different parts of the loop, might resume the normal
      unsynchronized activity of the basal ganglia circuitry, and, therefore,
      ameliorate the clinical symptoms of Parkinson's disease.

PMID- 11948752
TI  - Brainstem motor loops in the control of movement.
AB  - In recent years, the role of the area around the upper brainstem, particularly
      the pedunculopontine (PPN) region and the zona incerta (ZI), in the initiation
      and control of movement has generated much clinical interest. Using
      electrophysiological and pharmacological methods, we have further explored these
      structures and their influence in motor control in the nonhuman primate and in
      patients with proximal tremor. We have found that lesioning the PPN and
      electrical stimulation at high frequencies of the PPN region in the normal
      behaving primate induces akinesia, and low frequency stimulation can induce
      tremor. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) 
      treated parkinsonian primate model, bicuculline, a gamma-aminobutyric acid
      antagonist, can alleviate akinesia when infused into the PPN region. Further
      studies will elucidate the possible clinical implications of these observations.
      The ZI has reciprocal connections with several cortical areas, the upper
      brainstem, cerebellum, and thalamus. We have found that chronic, high-frequency
      deep brain stimulation of the ZI suppresses proximal limb tremor. Field potential
      recordings from the ZI show significant coherence with concurrent proximal muscle
      electromyograms. This finding has potential clinical relevance as proximal tremor
      generally does not respond well to thalamic surgery and may be severely
      disabling.

PMID- 11948754
TI  - Pathophysiology of nonparkinsonian tremors.
AB  - Patients with nonparkinsonian tremors are the second largest group treated with
      functional neurosurgery. We summarize the present pathophysiological knowledge of
      these conditions. Essential tremor (ET) may be due to oscillations within the
      olivocerebellar circuit. There is experimental evidence from animal models for
      such a mechanism, and clinical data indicate an abnormal function of the
      cerebellum in ET. Cerebellar tremor may be closely related to the tremor seen in
      advanced ET. The malfunction of the cerebellum causes a pathological feed-forward
      control. Additionally an oscillator within the cerebellum or its input/output
      pathways may cause cerebellar tremor. Almost nothing is known about the
      pathophysiology of dystonic tremor. Holmes tremor is based on a nigral and a
      cerebellar malfunction and presents clinically as the combination of tremor in
      Parkinson's disease and cerebellar tremor. Neuropathic tremor can be extremely
      disabling and is thought to be due to an abnormal interaction of the disturbances
      within the periphery and abnormal cerebellar feedback. Unlike the case of
      Parkinson's disease, functional neurosurgery of nonparkinsonian tremors is not
      yet based on a solid pathophysiological background.

PMID- 11948755
TI  - Pathophysiology of dystonia: a neuronal model.
AB  - Dystonia has commonly been thought to represent a disorder of basal ganglia
      function. Although long considered a hyperkinetic movement disorder, the evidence
      to support such a classification was based on the presence of excessive
      involuntary movement, not on physiological data. Only recently, with the return
      of surgical procedures using microelectrode guidance for the treatment of
      dystonia, has electrophysiological data demonstrated an alteration in mean
      discharge rate, somatosensory responsiveness and the pattern of neuronal activity
      in the basal ganglia thalamocortical motor circuit. Previous models of dystonia
      suggested that reduced mean discharge rates in the globus pallidus internus (GPi)
      led to unopposed increases in activity in the thalamocortical circuit that
      precipitated the development of involuntary movement associated with dystonia.
      This model has subsequently been modified given the clear improvement in dystonic
      symptoms following lesions in the GPi, a procedure that is associated with a
      further reduction in pallidal output. The improvement in dystonia following
      pallidal lesions is difficult to reconcile with the "rate" hypothesis for
      hypokinetic and hyperkinetic movement disorders and has led to the development of
      alternative models that, in addition to rate, incorporate changes in pattern,
      somatosensory responsiveness and degree of synchronization of neuronal activity.
      Present models of dystonia, however, must not only take these changes into
      account but must reconcile these changes with the reported changes in cortical
      excitability reported with transcranial magnetic stimulation, the changes in
      metabolic activity in cortical and subcortical structures documented by positron
      emission tomography (PET), and the alterations in spinal and brainstem reflexes.
      A model incorporating these changes together with the reported changes in
      neuronal activity in the basal ganglia and thalamus is presented.

PMID- 11948756
TI  - Mechanisms of deep brain stimulation.
AB  - High frequency electrical stimulation by means of electrodes implanted into the
      brain (deep brain stimulation; DBS) recently has become an accepted technique for
      the treatment of several movement disorders and in particular for Parkinson's
      disease. Because the effects produced by DBS are similar to those produced by
      making a lesion in the same region, it has been proposed that the overall effect
      of DBS is to inhibit the neural activity in the region stimulated. However,
      whether this is actually the case is presently not known, but various mechanisms
      have been proposed in an attempt to explain how DBS could mimic the effects of a
      lesion. We describe the various mechanisms that have been proposed to account for
      the inhibition or disruption of the pathologic outflow by high-frequency DBS,
      ranging from depolarisation block to stimulation-evoked release of gamma
      aminobutyric acid and describes preliminary findings that show that stimulation
      within these structures can result in inhibition.

PMID- 11948757
TI  - Mechanisms of deep brain stimulation: excitation or inhibition.
AB  - There is little debate that deep brain stimulation (DBS) has been an effective
      tool in the treatment of Parkinson's disease as well as other movement disorders.
      There remains however, considerable debate concerning the mechanism(s) underlying
      its beneficial effect. The comparable effect of stimulation to ablation in the
      thalamus on tremor, and in the subthalamic nucleus (STN) and internal segment of
      the globus pallidus (GPi) on the motor signs associated with PD, have led many
      investigators to conclude that DBS acts to suppress neuronal activity, decreasing
      output from the stimulated site. There are, however, data that do not support
      this argument. Microdialysis studies in GPi showed increased levels of glutamate
      during STN stimulation, suggesting activation of glutamatergic output from the
      STN to the GPi. Studies in parkinsonian primates have demonstrated increased mean
      discharge rates of neurons in GPi during chronic stimulation in STN, and GPi
      stimulation in humans has been associated with a suppression of neuronal activity
      in the thalamus. Contrary to what one would expect if stimulation inhibits output
      from the stimulated structure, stimulation in GPe has been demonstrated to
      improve bradykinesia. Although arguments for increased output from the stimulated
      structure seem to conflict with the hypothesis that stimulation acts to inhibit
      neuronal activity, it is possible to explain these observations through a common
      mechanism, e.g. activation of fiber pathways. Based on this mechanism, the effect
      of stimulation on cellular activity in the stimulated site would be increased or
      decreased dependent on the neurotransmitter of the afferent fibers projecting to
      that site. However, in addition to activation of afferent fibers, projection
      axons from neurons in the stimulated structure, also readily excitable by
      electrical stimulation, would also be tonically activated and discharge
      independently of the soma, thereby increasing output from the structure during
      extracellular stimulation. Thus, although high frequency stimulation may inhibit
      neurons via activation of inhibitory afferents, the output from that structure
      may be increased as the result of activation of axonal elements leaving the
      target structure. This hypothesis would explain the present experimental results,
      is consistent with excitability profiles of neuronal elements based on their
      biophysical properties, and fits with more recent models emphasizing the role of
      altered patterns of neuronal activity in the development of hypokinetic and
      hyperkinetic movement disorders.

PMID- 11948758
TI  - Mechanisms of deep brain stimulation.
AB  - The mechanism of action of high frequency deep brain stimulation is still
      unknown. However, in all circumstances and in all target nuclei so far
      stimulated, the effects mimic those of lesions previously made during
      thalamotomies, pallidotomies or even subthalamotomies, suggesting an inhibition
      of at least the neuronal network containing the target, if not of the target
      itself. On the contrary, fiber bundles are consistently activated at low or high
      frequencies. The hypothetical mechanisms envisioned should therefore be
      compatible and even produce these observed effects, to be acceptable as
      hypotheses. The mechanism could be either one or a combination of several causes:
      jamming of a feedback loop, activation of inhibitory structures included in a
      more complex network, blockade of membrane ion channels, deplorisation blockade,
      synaptic exhaustion, induction of early genes, changes in local blood flow,
      neuroplasticity, etc. It is probable that some are more involved in the acute
      effects and others in the long term changes, close to neuroplasticity. It is
      clear that the understanding of this strange and powerful phenomenon will profit
      from both clinical observation and well designed animal experiments.

PMID- 11948759
TI  - Treatment results: Parkinson's disease.
AB  - Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease
      that is applied to three targets: the ventral intermediate nucleus of the
      thalamus (Vim), the globus pallidus internas (GPi) and the subthalamic nucleus
      (STN). Vim DBS mainly improves contralateral tremor and, therefore, is being
      supplanted by DBS of the two other targets, even in patients with tremor dominant
      disease. STN and GPi DBS improve off-motor phases and dyskinesias. There is
      little comparative data between these procedures. The magnitude of the motor
      improvement seems more constant with STN than GPi DBS. STN DBS allows a decrease
      in antiparkinsonian drug doses and consumes moderate current. These advantages of
      STN over GPi DBS are offset by the need for more intensive postoperative
      management. The DBS procedure has the unique advantage of reversibility and
      adjustability over time. Patients with young-onset Parkinson's disease suffering
      from levodopa-induced motor complications but still responding well to levodopa
      and who exhibit no behavioral, mood, or cognitive impairment benefit the most
      from STN DBS. Adverse effects more specific of the DBS procedure are infection,
      cutaneous erosion, and lead breaking or disconnection. Intracranial electrode
      implantation can induce a hematoma or contusion. Most authors agree that the
      benefit to risk ratio of DBS is favorable.

PMID- 11948760
TI  - Stereotactic neurosurgery for tremor.
AB  - The role of the motor thalamus as surgical target in stereotactic neurosurgery
      for different kinds of tremor is discussed. For tremor in Parkinson's disease,
      the subthalamic nucleus becomes more and more often the surgical target, because
      this target also gives relief of other and more incapacitating symptoms
      (hypokinesia, rigidity). Stimulation is as effective in tremor suppression as
      coagulation but has less adverse events and permits bilateral surgery. In
      selected cases, thalamotomy can still be indicated.

PMID- 11948761
TI  - Results of deep brain stimulation for dystonia: a critical reappraisal.
AB  - Deep brain stimulation for severe dystonia is still in the very first stage of
      development. Only single case reports or small case series have been reported to
      date. Best results have been obtained with pallidal stimulation in patients with
      primary generalised dystonia, especially in DYT1 mutation carriers. In secondary
      dystonia, conflicting results were reported. However, there is today enough
      promising evidence for a striking efficacy of pallidal stimulation in dystonia,
      supporting the need for further investigations in the field, with collaborative
      projects (regarding to the limited number of eligible patients); double-blind
      studies, including a consensus about surgical method; and a precise anatomic
      analysis of the position of the electrode. A careful assessment of the efficacy
      by using improved clinical scale is also warranted.

PMID- 11948762
TI  - Deep brain stimulation for Parkinson's disease: patient selection and evaluation.
AB  - Critical to the successful application of deep brain stimulation for the
      treatment Parkinson's disease is the proper selection of patients who will
      reliably benefit from this procedure and the successful evaluation of the
      responses obtained. This review will discuss the various factors influencing
      patient selection and summarize the recommended approach to patient assessment by
      using the Core Assessment Program for Surgical Interventions and Transplantation
      in Parkinson's Disease (CAPSIT-PD).

PMID- 11948763
TI  - Deep brain stimulation for tremor [correction of trauma]: patient selection and
      evaluation.
AB  - The selection of patients with movement disorders for deep brain stimulation is
      becoming a common neurological and neurosurgical task. Deep brain stimulation is
      suitable for different forms of tremor, which can often not be treated with
      medication. This suitability applies for essential tremor, monosymptomatic tremor
      at rest, cerebellar or multiple sclerosis tremor, Holmes' tremor, primary writing
      tremor or tremor in neuropathies. The appropriate selection of patients is
      critical for the outcome of surgical relief of tremors. Considering the risks of
      any stereotactic intervention, the following must apply: (1) motor symptoms lead
      to a relevant disability in activities of daily living, despite optimal medical
      treatment; (2) biological age of the patient; (3) neurosurgical
      contraindications; (4) the patient is neither demented nor severely depressed. If
      these conditions are fulfilled, the individual chances of improvement of the
      target symptoms need to be checked, based on the following guidelines: (1) the
      kind of tremor, (2) the natural course of the tremor, (3) the chances for medical
      treatment in a particular patient, (4) the outcome of surgery in a specific
      condition, (5) the individual risks for a patient to suffer from complications.
      The outcome of surgery for tremor depends on the clinical type and distribution.
      Distal limb tremors are easier to treat than proximal limb tremors. Intention
      tremor is more difficult to treat than rest or postural tremor. The indication
      for surgical treatment depends on the analysis of the individual risk-benefit
      ratio, which also has to take into account the patients' social, professional,
      and familial background. The patient needs to be well informed about his
      individual risk-benefit ratio and of alternative treatments, before undergoing
      stereotactic surgery.

PMID- 11948764
TI  - Deep brain stimulation for dystonia: patient selection and evaluation.
AB  - Deep brain stimulation (DBS) for dystonia still needs to be considered
      investigational, because there are no controlled studies for this indication, the
      optimal target point is uncertain, and long-term effects are unknown. The
      striking improvement of levodopa-induced dyskinesias in Parkinson's disease by
      deep brain stimulation of the internal pallidum has encouraged the use of this
      therapy for generalized and severe segmental dystonia in children and adults.
      Single case and small cohort studies have reported impressive efficacy of
      pallidal DBS in patients with primary dystonia, especially DYT1 mutation
      carriers, but results in secondary dystonia are less conclusive. This article
      discusses the different factors influencing patient selection for surgical
      treatment and describes standardized methods and the caveats for clinical
      documentation of treatment results in dystonia.

PMID- 11948765
TI  - Neuropsychological assessment for management of patients with deep brain
      stimulation.
AB  - The inclusion of cognitive and behavioural criteria has been recommended for the
      management of patients with deep brain stimulation. A neuropsychological
      assessment may contribute to different issues: (1) selection of the best
      candidates for surgery, (2) evaluation of the consequences of surgery, (3)
      research of the best electrode implantation. Recent neuropsychological studies
      indicate that (1) with appropriate inclusion criteria, the effects of surgery on
      cognitive functions are limited; (2) an aggravation of behavioural disorders
      might be related to subthalamic nucleus (STN) stimulation and depend on electrode
      location; (3) subthalamic nucleus stimulation, but not the internal globus
      pallidus stimulation, improves psychomotor efficiency and working memory. These
      results would suggest that the implanted electrodes are not solely targeting the
      motor circuit and that the cognitive and motor circuits are not completely
      segregated.

PMID- 11948766
TI  - Imaging of subthalamic nucleus and ventralis intermedius of the thalamus.
AB  - The techniques of targeting the subthalamic nucleus (STN) and the ventralis
      intermedius nucleus (Vim) are similar, only the coordinates are different.
      Targeting ideally consists of gathering all data about a target and positioning
      the electrode correctly within that target. The electrode should be positioned
      within a statistical range of coordinates, where the neuronal firing fits a given
      pattern and responds to external stimuli, particularly to proprioceptive inputs,
      in a somatotopically organized manner. Moreover, final placement should provide
      the best clinical improvement of symptoms under the stimulation parameters
      expected to be used in the long term. This latter criterion is by far the most
      important, because intraoperative findings indicate the functional benefit for
      the patient, which is the ultimate purpose of this surgery. A variety of
      radiological modalities are available to provide data for electrode placement,
      but each type has its drawbacks. Ventriculography, although safe when performed
      accordingly to strict technical procedure, is the most precise method but
      provides more indirect targeting and is more invasive than magnetic resonance
      imaging (MRI). MRI is the best method for visualizing the STN and, to some
      extent, for discerning the Vim, but it is plagued with unpredictable and
      nonreproducible deformations that induce a systematic distortion. These
      shortcomings no doubt will be corrected in the near future, and the technologies
      will better assist us in the proper placement of electrodes, which will provide
      the patient with the highest possible benefit.

PMID- 11948767
TI  - Stereotactic imaging of the pallidal target.
AB  - In 48 consecutive patients, we applied a new stereotactic imaging technique to
      individually visualize the pallidal target before surgery. A turbo spin-echo
      proton density sequence (acquisition time, 6 minutes 5 seconds) was used for 2-mm
      thick contiguous axial scanning. Pallidocapsular border, medial putaminal border,
      and optic tract were visualized bilaterally in all patients. Boundaries of globus
      pallidus internus, globus pallidus externus, and lamina medullaris interna were
      clearly visualised in 71% of the patients. The anatomic target point was chosen
      in the middle of the visualized posteroventral pallidum, irrespective of the
      position of this point in relation to commissures. The lateralities of
      pallidocapsular border, lamina medullaris interna, and medial boundary of putamen
      were measured bilaterally in each patient, and the width of the posteroventral
      pallidum was assessed. The laterality of structures (measured from a point 2 mm
      anterior to midcommissural point and at a level 2-4 mm below anterior commissure
      posterior commissure line) showed a wide range. The position of the
      pallidocapsular border varied by up to almost 1 cm between the most medial and
      the most lateral one. There were also variations in the position of the pallidal
      structures between left and right hemispheres in the same patients. The
      posteroventral pallidum was slightly more wide on the left than the right side.
      Given the significant inter- and intra-individual variabilities of the position
      of pallidal structures, it may be hazardous to rely solely on the atlas and the
      commissures for targeting. A magnetic resonance imaging sequence that enables
      visualization in each individual patient of the target area and its surroundings
      may contribute to less electrode passes during intraoperative physiological
      exploration and to more exact location of the lesion or chronic electrode in the
      posteroventral pallidum.

PMID- 11948768
TI  - Intraoperative microelectrode and semi-microelectrode recording during the
      physiological localization of the thalamic nucleus ventral intermediate.
AB  - We review the techniques of physiological localization of the site for ventralis
      intermedius (Vim) thalamotomy or implantation of Vim-deep brain stimulation (DBS)
      for treatment of parkinsonian, essential, and intention tremor. Both
      microelectrode and semi-microelectrode techniques are reviewed. We believe the
      use of microelectrode and semi-microelectrode recordings in combination with
      Radiological landmarks provide the most accurate localization of the target. In
      addition to recording, microstimulation of subcortical structures such as Vim and
      thalamic nucleus ventralis caudal through the microelectrode may improve
      physiological identification by altering the tremor and evoking somatic
      sensations, respectively. Microelectrode recording provides the highest
      resolution picture of the target site at a cost of increased time to locate the
      target. We also review the relationship between thalamic neuronal firing and
      electromyographic activity during tremor. Implications of these results for the
      mechanisms for parkinsonian, essential, and intention tremors are discussed.

PMID- 11948770
TI  - Microelectrode recordings in the pallidum.
AB  - The internal segment of the globus pallidus (GPi) is being targeted in
      neurosurgical procedures to treat Parkinson's disease and dystonia. Precise
      targeting of the pallidal complex is important in determining the efficacy of the
      surgical intervention and for the avoidance of adverse effects. Intraoperative
      microelectrode recording can be used to characterize the patterns of activity and
      receptive field properties of single pallidal neurons and to identify important
      bordering structures, including the optic tract and internal capsule. Because the
      clinical features of movement disorders can be differentially affected as a
      function of location within the pallidal complex, further refinements in
      intraoperative targeting may become important.

PMID- 11948769
TI  - Intraoperative microrecordings of the subthalamic nucleus in Parkinson's disease.
AB  - Microelectrode recordings of single unit neuronal activity were used during
      stereotactic surgery to define the subthalamic nucleus for chronic deep brain
      stimulation in the treatment of Parkinson's disease. By using five parallel
      trajectories, often two to three microelectrodes allow us to recognize
      subthalamic nucleus (STN) neuronal activity. STN neurons were easily
      distinguished from cells of the overlying zona incerta and the underlying
      substantia nigra. During a typical exploratory track, we can observe a very low
      background noise in the zona incerta and almost complete absence of single cell
      recording. Penetration of the electrode tip into the STN is characterized by a
      sudden increase in background activity and single cell activity of spontaneously
      active neurons. The exit of electrode tip out of the STN corresponds to a
      decrease in background noise and a loss of single cell activity. Spontaneous
      neuronal activity increases again when the electrode tips enters the substantia
      nigra pars reticulata (SNr); however, the activity is less rich than in the STN,
      indicating a more cell-sparse nucleus. STN neurons are characterized by a mean
      firing rate of 42.30 +/- 22.00 spikes/sec (mean +/- SD). The STN cells exhibited
      irregular or bursty discharge pattern. The pattern of single cell activity in the
      SNr is a more regular tonic activity that can easily be distinguished from the
      bursting pattern in the STN. The most useful criteria to select a trajectory are
      (1) the length of an individual trajectory displaying typical STN activity, (2)
      the bursting pattern of activity, and (3) motor responses typical of the
      sensorimotor part of the nucleus. In conclusion, microelectrode recording of the
      subthalamic area improves the accuracy of targeting the STN.

PMID- 11948771
TI  - Intraoperative micro- and macrostimulation of the subthalamic nucleus in
      Parkinson's disease.
AB  - Studying the clinical effects induced by electrical stimulation of the
      subthalamic nucleus (STN) area in a parkinsonian patient under local anesthesia
      is a mandatory step to determine the precise location of the final chronic
      electrode. Using multiple microelectrodes, preferably in a concentric parallel
      array allows a precise mapping of the STN region. The most reliable features to
      determine the suitable target are stimulation-induced dyskinesias and rigidity
      decrease at a low intensity without adverse effects or only at far higher
      intensities. New skills are needed to assess all stimulation-induced effects and
      interpret them in anatomo-functional terms.

PMID- 11948772
TI  - Complications of deep brain stimulation surgery.
AB  - Currently, DBS is a commonly performed surgery for treatment of movement
      disorders, especially Parkinson's disease. Although nonablative and minimally
      invasive, this procedure may give rise to many complications and side effects,
      some of which are neither reversible nor adaptable. This study reviews the
      potential complications of DBS along the entire path of this procedure, from
      patient selection through the postoperative period. Although intraoperative
      complications such as paralysis and hematoma are rare, other serious
      complications due to the hardware, such as lead fracture, dislocation, and
      infection, are not uncommon. Complications or side effects as a result of chronic
      stimulation itself may be the most common. It is concluded that every member of
      the surgical team, including the referring neurologist, has an important role in
      the avoidance of such complications. Proper and careful patient selection,
      matching each patient to the specific DBS procedure appropriate for his/her
      symptom profile and suitable for his/her social and cognitive condition, along
      with experienced and careful intraoperative surgical routine, may be the best way
      to prevent the complications of DBS procedures.

PMID- 11948773
TI  - Documentation of electrode localization.
AB  - In evaluating the success of deep brain stimulation (DBS), the benefit for the
      patient is the most important criteria. Nevertheless, correct placement of
      electrodes should also be determined in terms of their anatomic position.
      Therefore, we propose a suite of different imaging modalities and further
      processing, which leads to an exact anatomic and statistically comparable
      documentation of electrode localization. Forty-three consecutive patients with a
      total of 85 implanted DBS electrodes were evaluated with respect to postoperative
      imaging. T1-weighted magnetic resonance imaging (T1-MRI) was performed in all
      patients, 34 patients received T2-MRI, in 18 patients stereotactic X-ray of the
      scull was performed in anteroposterior and lateral projections, whereas 6
      patients were additionally evaluated by pre- and postoperative MR-image fusion
      between T1-data sets and calculation of coordinates for electrode contacts. In T1
      MRI, the artefacts of each electrode contact could be delineated in relation to
      anatomic reference structures, whereas T2-MRI allowed reproducibly for
      delineation of electrode artefacts within subthalamic nucleus or globus pallidus
      pars interna. By MR-image fusion it could be shown that the difference between
      planned target coordinates and coordinates of the active electrode contact ranged
      below 1 mm except for the z axis. The comparison with values obtained from
      stereotactic X-ray confirmed these results. The sequential and complementary use
      of the described imaging modalities and further image processing provide
      clinically reliable and statistically comparable results to prove the exact
      anatomic electrode positioning in DBS in addition to the objective and subjective
      improvements of the patients' symptoms.

PMID- 11948774
TI  - Hardware-related problems of deep brain stimulation.
AB  - Deep brain stimulation for the alleviation of movement disorders and pain is now
      an established therapy. However, very little has been published on the topic of
      hardware failure in the treatment of such conditions irrespective of clinical
      outcome. Such device-related problems lead to significant patient morbidity and
      increased cost of therapy in the form of prolonged antibiotics, in-patient
      hospitalization, repeat surgery, and device replacement. We report a prospective
      review of our experience at the Radcliffe Infirmary Oxford from the period of
      April 1998 to March 2001. Overall there is a 20% rate of hardware-related
      problems in this series, which falls between the 7% and 65% rates reported by
      other groups. The majority of these failures occurred early on in the series, and
      numbers declined with experience. Some of the problems may be idiosyncratic to
      the methodology of individual groups.

PMID- 11948775
TI  - Introduction to the programming of deep brain stimulators.
AB  - The clinical success of deep brain stimulation (DBS) for treating Parkinson's
      disease, tremor, or dystonia critically depends on the quality of postoperative
      neurologic management. Movement disorder specialists becoming involved with this
      therapy need to acquire new skills to optimally adapt stimulation parameters and
      medication after implantation of a DBS system. In clinical practice, the infinite
      number of possible parameter settings in DBS can be reduced to few relevant
      combinations. In this article, the authors describe a general scheme of selecting
      stimulation parameters in DBS and provide clinical and neurophysiological
      arguments for such a standardized algorithm. They also describe noninvasive
      technical trouble shooting by using programming features of the commercially
      available neurostimulation devices.

PMID- 11948776
TI  - Postoperative management of subthalamic nucleus stimulation for Parkinson's
      disease.
AB  - The postoperative neurologic management of patients with deep brain stimulation
      (DBS) of the subthalamic nucleus (STN) for Parkinson' s disease is a complex
      dynamic process that involves a progressive increase in stimulation intensity and
      a parallel decrease in antiparkinsonian medication while assessing the
      interactions of both treatments. Neurologists responsible for postoperative
      management of patients receiving STN DBS must have expert knowledge of the
      electroanatomy of the subthalamic area and be familiar with the medical treatment
      of motor and nonmotor symptoms, including the management of long-term
      complications of levodopa treatment. Neurosurgeons who perform DBS need to
      understand the principles that guide the postoperative adaptation of treatment.
      This article defines guidelines for setting stimulation parameters, adapting
      drugs and managing adverse effects.

PMID- 11948777
TI  - Methods for programming and patient management with deep brain stimulation of the
      globus pallidus for the treatment of advanced Parkinson's disease and dystonia.
AB  - Globus pallidus (GPi) deep brain stimulation can markedly improve severe
      medication-refractory Parkinson's disease (PD) and dystonia. Appropriate
      perioperative patient management can assist with electrode implantation.
      Optimizing stimulation settings and simultaneously adjusting medications (when
      appropriate) can substantially improve patient outcomes. Although there are a
      large number of possible stimulation settings, in clinical practice, a relatively
      narrow range of settings has been shown to be most efficacious. A systematic
      approach to determining those settings that maximally improve parkinsonism and
      suppress drug-induced dyskinesias is outlined following a clear algorithm that
      uses the observation that stimulation of the dorsal and ventral pallidum has been
      shown to have opposite motor effects in PD. Based on the available literature,
      recommendations are also made for the use of GPi deep brain stimulation in
      dystonia.

PMID- 11948778
TI  - Postoperative management of Vim DBS for tremor.
AB  - Stimulation of the ventralis intermedius (Vim) is a treatment of severe tremor
      from various origins. The adjustment of electrical parameters is done when the
      lesion-like effects of the implant disappear. Each contact is assessed
      successively, by using a constant pulse width of 60 microsec and a frequency of
      130 Hz or above and progressively increasing the voltage. At the same time, the
      tremor and possible side effects are monitored. The most frequent side effects
      are paresthesias, dysarthria, muscle contractions related to stimulation of the
      pyramidal tract, and cerebellar syndrome. Medications have to be adjusted slowly,
      and often, particularly in case of Parkinson's disease, it is difficult to
      decrease the dosage. It is important to teach the patient to switch the
      stimulator on or off and check that it is working. Patients need to be seen
      within the 3 months after implant, then occasionally according to the effect. In
      the long-term, some patients will develop some rebound of tremor when they switch
      off and/or some tolerance to the effect of the stimulator, which can be difficult
      to manage. In case of Parkinson's disease, motor fluctuations and dyskinesias,
      that does not respond to Vim stimulation, can occur.

PMID- 11948780
TI  - C-terminal domain of gyrase A is predicted to have a beta-propeller structure.
AB  - Two different type II topoisomerases are known in bacteria. DNA gyrase (Gyr)
      introduces negative supercoils into DNA. Topoisomerase IV (Par) relaxes DNA
      supercoils. GyrA and ParC subunits of bacterial type II topoisomerases are
      involved in breakage and reunion of DNA. The spatial structure of the C-terminal
      fragment in GyrA/ParC is not available. We infer homology between the C-terminal
      domain of GyrA/ParC and a regulator of chromosome condensation (RCC1), a
      eukaryotic protein that functions as a guanine-nucleotide-exchange factor for the
      nuclear G protein Ran. This homology, complemented by detection of 6 sequence
      repeats with 4 predicted beta-strands each in GyrA/ParC sequences, allows us to
      predict that the GyrA/ParC C-terminal domain folds into a 6-bladed beta
      propeller. The prediction rationalizes available experimental data and sheds
      light on the spatial properties of the largest topoisomerase domain that lacks
      structural information.

PMID- 11948781
TI  - Simulations of ion current in realistic models of ion channels: the KcsA
      potassium channel.
AB  - Realistic studies of ion current in biologic channels present a major challenge
      for computer simulation approaches. All-atom molecular dynamics simulations
      involve serious time limitations that prevent their use in direct evaluation of
      ion current in channels with significant barriers. The alternative use of
      Brownian dynamics (BD) simulations can provide the current for simplified
      macroscopic models. However, the time needed for accurate calculations of
      electrostatic energies can make BD simulations of ion current expensive. The
      present work develops an approach that overcomes some of the above challenges and
      allows one to simulate ion currents in models of biologic channels. Our method
      provides a fast and reliable estimate of the energetics of the system by
      combining semimacroscopic calculations of the self-energy of each ion and an
      implicit treatment of the interactions between the ions, as well as the
      interactions between the ions and the protein-ionizable groups. This treatment
      involves the use of the semimacroscopic version of the protein dipole Langevin
      dipole (PDLD/S) model in its linear response approximation (LRA) implementation,
      which reduces the uncertainties about the value of the protein "dielectric
      constant." The resulting free energy surface is used to generate the forces for
      on-the-fly BD simulations of the corresponding ion currents. Our model is
      examined in a preliminary simulation of the ion current in the KcsA potassium
      channel. The complete free energy profile for a single ion transport reflects
      reasonable energetics and captures the effect of the protein-ionized groups. This
      calculated profile indicates that we are dealing with the channel in its closed
      state. Reducing the barrier at the gate region allows us to simulate the ion
      current in a reasonable computational time. Several limiting cases are examined,
      including those that reproduce the observed current, and the nature of the
      productive trajectories is considered. The ability to simulate the current in
      realistic models of ion channels should provide a powerful tool for studies of
      the biologic function of such systems, including the analysis of the effect of
      mutations, pH, and electric potentials.

PMID- 11948782
TI  - Docking unbound proteins using shape complementarity, desolvation, and
      electrostatics.
AB  - A comprehensive docking study was performed on 27 distinct protein-protein
      complexes. For 13 test systems, docking was performed with the unbound X-ray
      structures of both the receptor and the ligand. For the remaining systems, the
      unbound X-ray structure of only molecule was available; therefore the bound
      structure for the other molecule was used. Our method optimizes desolvation,
      shape complementarity, and electrostatics using a Fast Fourier Transform
      algorithm. A global search in the rotational and translational space without any
      knowledge of the binding sites was performed for all proteins except nine
      antibodies recognizing antigens. For these antibodies, we docked their well
      characterized binding site-the complementarity-determining region defined without
      information of the antigen-to the entire surface of the antigen. For 24 systems,
      we were able to find near-native ligand orientations (interface C(alpha) root
      mean square deviation less than 2.5 A from the crystal complex) among the top
      2,000 choices. For three systems, our algorithm could identify the correct
      complex structure unambiguously. For 13 other complexes, we either ranked a near
      native structure in the top 20 or obtained 20 or more near-native structures in
      the top 2,000 or both. The key feature of our algorithm is the use of target
      functions that are highly tolerant to conformational changes upon binding. If
      combined with a post-processing method, our algorithm may provide a general
      solution to the unbound docking problem. Our program, called ZDOCK, is freely
      available to academic users (http://zlab.bu.edu/~rong/dock/).

PMID- 11948783
TI  - Identifying proteins of high designability via surface-exposure patterns.
AB  - Using an off-lattice model, we fully enumerate folded conformations of
      polypeptide chains of up to N = 19 monomers. Structures are found to differ
      markedly in designability, defined as the number of sequences with that structure
      as a unique lowest-energy conformation. We find that designability is closely
      correlated with the pattern of surface exposure of the folded structure. For
      longer chains, complete enumeration of structures is impractical. Instead,
      structures can be randomly sampled, and relative designability estimated either
      from designability within the random sample, or directly from surface-exposure
      pattern. We compare the surface-exposure patterns of those structures identified
      as highly designable to the patterns of naturally occurring proteins.

PMID- 11948784
TI  - Weak temperature dependence of the free energy surface and folding pathways of
      structured peptides.
AB  - The thermodynamics and energetics of a 20-residue synthetic peptide with a stable
      three-stranded antiparallel beta-sheet fold are investigated by implicit solvent
      molecular dynamics (MD) at 330 K (slightly above the melting temperature in the
      model) and compared with previous simulation results at 360 K. At both
      temperature values, the peptide folds reversibly to the NMR solution
      conformation, irrespective of the starting conformation. The sampling of the
      conformational space (2.3 micros and 25 folding events at 330 K, and 3 micros and
      50 folding events at 360 K) is sufficient to obtain a thermodynamic description
      of minima and transition states on the free energy surface, which is determined
      near equilibrium by counting populations. The free energy surface, plotted as a
      function of two-order parameters that monitor formation of either of the beta
      hairpins, is similar at both temperature values. The statistically predominant
      folding pathway and its frequency (about two-thirds of the folding events) are
      the same at 330 K and 360 K. Furthermore, the main unfolding route is the reverse
      of the predominant folding pathway. The effective energy and its electrostatic
      and van der Waals contributions show a downhill profile at both temperatures,
      implying that the free energy barrier is of entropic origin and corresponds to
      the freezing of about two-thirds of the chain into a beta-hairpin conformation.
      The average folding rate is nearly the same at 330 K and 360 K, while the
      unfolding rate is about four times slower at 330 K than at 360 K. Taken together
      with previous MD analysis of alpha-helices and beta-hairpins, the present
      simulation results indicate that the free energy surface and folding mechanism of
      structured peptides have a weak temperature dependence.

PMID- 11948785
TI  - Geometry and physics of proteins.
AB  - A conceptual framework for understanding the protein folding problem has remained
      elusive in spite of many significant advances. We show that geometrical
      constraints imposed by chain connectivity, compactness, and the avoidance of
      steric clashes can be encompassed in a natural way using a three-body potential
      and lead to a selection in structure space, independent of chemical details.
      Strikingly, secondary motifs such as hairpins, sheets, and helices, which are the
      building blocks of protein folds, emerge as the chosen structures for segments of
      the protein backbone based just on elementary geometrical considerations.

PMID- 11948786
TI  - Coupling of ligand binding and dimerization of helix-loop-helix peptides:
      spectroscopic and sedimentation analyses of calbindin D9k EF-hands.
AB  - Isolated Ca2+-binding EF-hand peptides have a tendency to dimerize. This study is
      an attempt to account for the coupled equilibria of Ca2+-binding and peptide
      association for two EF-hands with strikingly different loop sequence and net
      charge. We have studied each of the two separate EF-hand fragments from calbindin
      D9k. A series of Ca2+-titrations at different peptide concentrations were
      monitored by CD and fluorescence spectroscopy. All data were fitted
      simultaneously to both a complete model of all possible equilibrium intermediates
      and a reduced model not including dimerization in the absence of Ca2+. Analytical
      ultracentrifugation shows that the peptides may occur as monomers or dimers
      depending on the solution conditions. Our results show strikingly different
      behavior for the two EF-hands. The fragment containing the N-terminal EF-hand
      shows a strong tendency to dimerize in the Ca2+-bound state. The average Ca2+
      affinity is 3.5 orders of magnitude lower than for the intact protein. We observe
      a large apparent cooperativity of Ca2+ binding for the overall process from Ca2+
      free monomer to fully loaded dimer, showing that a Ca2+-free EF-hand folds upon
      dimerization to a Ca2+-bound EF-hand, thereby presenting a preformed binding site
      to the second Ca2+-ion. The C-terminal EF-hand shows a much smaller tendency to
      dimerize, which may be related to its larger net negative charge. In spite of the
      differences in dimerization behavior, the Ca2+ affinities of both EF-hand
      fragments are similar and in the range lgK = 4.6-5.3.

PMID- 11948787
TI  - Dissecting protein-protein recognition sites.
AB  - The recognition sites in 70 pairwise protein-protein complexes of known three
      dimensional structure are dissected in a set of surface patches by clustering
      atoms at the interface. When the interface buries <2000 A2 of protein surface,
      the recognition sites usually form a single patch on the surface of each
      component protein. In contrast, larger interfaces are generally multipatch, with
      at least one pair of patches that are equivalent in size to a single-patch
      interface. Each recognition site, or patch within a site, contains a core made of
      buried interface atoms, surrounded by a rim of atoms that remain accessible to
      solvent in the complex. A simple geometric model reproduces the number and
      distribution of atoms within a patch. The rim is similar in composition to the
      rest of the protein surface, but the core has a distinctive amino acid
      composition, which may help in identifying potential protein recognition sites on
      single proteins of known structures.

PMID- 11948788
TI  - Structural analysis, identification, and design of calcium-binding sites in
      proteins.
AB  - Assigning proteins with functions based on the 3-D structure requires high-speed
      techniques to make a systematic survey of protein structures. Calcium regulates
      many biological systems by binding numerous proteins in different biological
      environments. Despite the great diversity in the composition of ligand residues
      and bond angles and lengths of calcium-binding sites, our structural analysis of
      11 calcium-binding sites in different classes of proteins has shown that common
      local structural parameters can be used to identify and design calcium-binding
      proteins. Natural calcium-binding sites in both EF-hand proteins and non-EF-hand
      proteins can be described with the smallest deviation from the geometry of an
      ideal pentagonal bipyramid. Further, two different magnesium-binding sites in
      parvalbumin and calbindin(D9K) can also be identified using an octahedral
      geometry. Using the established method, we have designed de novo calcium-binding
      sites into the scaffold of non-calcium-binding proteins CD2 and Rop. Our results
      suggest that it is possible to identify calcium- and magnesium-binding sites in
      proteins and design de novo metal-binding sites.

PMID- 11948789
TI  - Molecular dynamics simulations of the acyl-enzyme and the tetrahedral
      intermediate in the deacylation step of serine proteases.
AB  - Despite the availability of many experimental data and some modeling studies,
      questions remain as to the precise mechanism of the serine proteases. Here we
      report molecular dynamics simulations on the acyl-enzyme complex and the
      tetrahedral intermediate during the deacylation step in elastase catalyzed
      hydrolysis of a simple peptide. The models are based on recent crystallographic
      data for an acyl-enzyme intermediate at pH 5 and a time-resolved study on the
      deacylation step. Simulations were carried out on the acyl enzyme complex with
      His-57 in protonated (as for the pH 5 crystallographic work) and deprotonated
      forms. In both cases, a water molecule that could provide the nucleophilic
      hydroxide ion to attack the ester carbonyl was located between the imidazole ring
      of His-57 and the carbonyl carbon, close to the hydrolytic position assigned in
      the crystal structure. In the "neutral pH" simulations of the acyl-enzyme
      complex, the hydrolytic water oxygen was hydrogen bonded to the imidazole ring
      and the side chain of Arg-61. Alternative stable locations for water in the
      active site were also observed. Movement of the His-57 side-chain from that
      observed in the crystal structure allowed more solvent waters to enter the active
      site, suggesting that an alternative hydrolytic process directly involving two
      water molecules may be possible. At the acyl-enzyme stage, the ester carbonyl was
      found to flip easily in and out of the oxyanion hole. In contrast, simulations on
      the tetrahedral intermediate showed no significant movement of His-57 and the
      ester carbonyl was constantly located in the oxyanion hole. A comparison between
      the simulated tetrahedral intermediate and a time-resolved crystallographic
      structure assigned as predominantly reflecting the tetrahedral intermediate
      suggests that the experimental structure may not precisely represent an optimal
      arrangement for catalysis in solution. Movement of loop residues 216-223 and P3
      residue, seen both in the tetrahedral simulation and the experimental analysis,
      could be related to product release. Furthermore, an analysis of the geometric
      data obtained from the simulations and the pH 5 crystal structure of the acyl
      enzyme suggests that since His-57 is protonated, in some aspects, this crystal
      structure resembles the tetrahedral intermediate.

PMID- 11948790
TI  - Positioning of anchor groups in protein loop prediction: the importance of
      solvent accessibility and secondary structure elements.
AB  - The prediction of loop regions in the process of protein structure prediction by
      homology is still an unsolved problem. In an earlier publication, we could show
      that the correct placement of the amino acids serving as an anchor group to be
      connected by a loop fragment with a predicted geometry is a highly important step
      and an essential requirement within the process (Lessel and Schomburg, Proteins
      1999; 37:56-64). In this article, we present an analysis of the quality of
      possible loop predictions with respect to gap length, fragment length, amino acid
      type, secondary structure, and solvent accessibility. For 550 insertions and 544
      deletions, we test all possible positions for anchor groups with an inserted loop
      of a length between 3 and 12 amino acids. We could show that approximately 80% of
      the indel regions could be predicted within 1.5 A RMSD from a knowledge-based
      loop data base if criteria for the correct localization of anchor groups could be
      found and the loops can be sorted correctly. From our analysis, several
      conclusions regarding the optimal placement of anchor groups become obvious: (1)
      The correct placement of anchor groups is even more important for longer gap
      lengths, (2) medium length fragments (length 5-8) perform better than short or
      long ones, (3) the placement of anchor groups at hydrophobic amino acids gives a
      higher chance to include the best possible loop, (4) anchor groups within
      secondary structure elements, in particular beta-sheets are suitable, (5) amino
      acids with lower solvent accessibility are better anchor group. A preliminary
      test using a combination of the anchor group positioning criteria deduced from
      our analysis shows very promising results.

PMID- 11948792
TI  - Increasing the precision of comparative models with YASARA NOVA--a self
      parameterizing force field.
AB  - One of the conclusions drawn at the CASP4 meeting in Asilomar was that applying
      various force fields during refinement of template-based models tends to move
      predictions in the wrong direction, away from the experimentally determined
      coordinates. We have derived an all-atom force field aimed at protein and
      nucleotide optimization in vacuo (NOVA), which has been specifically designed to
      avoid this problem. NOVA resembles common molecular dynamics force fields but has
      been automatically parameterized with two major goals: (i) not to make high
      resolution X-ray structures worse and (ii) to improve homology models built by
      WHAT IF. Force-field parameters were not required to be physically correct;
      instead, they were optimized with random Monte Carlo moves in force-field
      parameter space, each one evaluated by simulated annealing runs of a 50-protein
      optimization set. Errors inherent to the approximate force-field equation could
      thus be canceled by errors in force-field parameters. Compared with the
      optimization set, the force field did equally well on an independent validation
      set and is shown to move in silico models closer to reality. It can be applied to
      modeling applications as well as X-ray and NMR structure refinement. A new method
      to assign force-field parameters based on molecular trees is also presented. A
      NOVA server is freely accessible at http://www.yasara.com/servers

PMID- 11948791
TI  - Native and non-native interactions along protein folding and unfolding pathways.
AB  - Go-type models, which include only native contact interactions in the energy
      function, are being used increasingly to describe the protein folding reaction.
      To investigate the validity of such models, we determine the role of native and
      non-native interactions along folding and unfolding pathways. For this purpose,
      we use a molecular mechanics energy function with an implicit solvation model (an
      effective energy function or potential of mean force) that can be expressed in a
      pairwise decomposable form. We find that for the native state and a wide range of
      other configurations, the contact energy is an accurate description, in part due
      to the cancellation of non-zero contributions from more distant residues.
      However, significant errors in the energy are introduced for non-native
      structures if the energy is calculated from the native contacts alone. Non-native
      contacts tend to make a significant contribution, particularly for molten
      globules and collapsed states along the unfolding pathways. The implication of
      these results for the use of Go-type models in studies of protein folding are
      discussed.

PMID- 11948793
TI  - Crystal structure of the Escherichia coli SbmC protein that protects cells from
      the DNA replication inhibitor microcin B17.

PMID- 11948794
TI  - Ureaplasma urealyticum biovar determination in women attending a family planning
      clinic in Guine-Bissau, using polymerase chain reaction of the multiple-banded
      antigen gene.
AB  - Although Ureaplasma urealyticum is commonly found in the genital tract of
      asymptomatic women, it has been suggested that only certain subgroups of this
      microorganism are disease associated. Vaginal specimens were collected to
      determine the distribution of U. urealyticum biovars and to estimate their
      possible association with age, absence of lactobacilli, and tetracycline
      resistance. Of the 94 women studied, 40 (43%) carried U. urealyticum and were
      biotyped by polymerase chain reaction (PCR). Twenty-nine (73%) strains presented
      with parvo biovar, 10 (25%) with T960 biovar, and one (2.5%) with both biovars.
      Parvo biovar was predominant in all age groups and appears to be more frequent in
      women 20-25 years of age (41%), whereas T960 was common in women 30-35 years of
      age (22%). In this study, U. urealyticum was not associated with changes in
      vaginal flora, although the inverse apparently was true for Mycoplasma hominis.
      However, T960 biovar was more associated with the loss of lactobacilli than was
      parvo biovar. The number of T960 biovar strains that presented tetracycline (40%)
      or multiple (100%) resistance was higher than that of parvo biovar strains (27%
      and 69%, respectively).

PMID- 11948795
TI  - Genotype resistance profiles in patients failing an NNRTI-containing regimen, and
      modifications after stopping NNRTI therapy.
AB  - Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) develops
      quickly and independently if they are used in combination with NRTIs or protease
      inhibitors (PIs) as rescue therapy, mainly due to the low genetic barrier of this
      class of drugs. In this study we examined clinical, therapeutic, and virologic
      characteristics in 88 patients with mutations conferring resistance to NNRTIs,
      and in 11 patients 1 year after stopping NNRTI therapy. Between patients
      administered Nevirapine (NVP) and those taking Efavirenz (EFV), no statistical
      differences were found in CD4 cell count, HIV viral load, time on NNRTI therapy,
      or number of PIs administered previously. A slow decline in the detectability of
      mutations encoding NNRTI resistance was found.

PMID- 11948796
TI  - Expression of CD66a in multiple myeloma.
AB  - CD66a is a member of the carcinoembryonic antigen family and has been suggested
      to function as an intercellular adhesion molecule and cell growth regulator.
      Expression of CD66a in myeloma cells was examined with mAb TS135 against CD66a
      transfectants of murine-transformed fibroblasts. The reactivity of mAb TS135 with
      CD66a, CD66c, and CD66e was revealed. CD66a in myeloma cells was considered to be
      detectable with this mAb, since CD66c and CD66e are not expressed in them. CD66a
      was detected in three myeloma cell lines and an IgM-producing B-cell line. In
      clinical bone marrow specimens, including 18 multiple myeloma, two primary
      macroglobulinemia, and a case of CLL-like chronic lymphoproliferation with
      monoclonal IgG production, CD66a and three conventional myeloma cell markers (PCA
      1, CD38, and CD56) were examined by indirect immunofluorescence assay. The
      results showed that 18 out of 21 cases (86%) were CD66a+, and PCA-1 showed the
      highest correlation with CD66a among conventional markers. Primary
      macroglobulinemia and chronic lymphoproliferation were also CD66a+. Two
      dimensional flow cytometry with mAbs TS135 and CD38 confirmed the reactivity of
      TS135 with myeloma cells in those bone marrow specimens. The findings suggest
      that CD66a is expressed in multiple myeloma with high frequency.

PMID- 11948797
TI  - Possible automatic cell classification of bone marrow aspirate using the CELL-DYN
      4000 automatic blood cell analyzer.
AB  - In clinical hematology, the demand for bone marrow aspiration testing is
      increasing. However, conventional automatic blood cell analyzers cannot
      completely analyze erythroblasts, and evaluation has mainly been performed by
      visual examination (the microscopic method). Using the CELL-DYN 4000 automatic
      blood cell analyzer (CD4000) (Abbott Laboratories, North Chicago, IL), specific
      recognition and classification of erythroblasts by DNA staining is possible. In
      the present study, using bone marrow blood collected from normal subjects and
      patients with hematological malignancy, we classified cells by the microscopic
      method and with the CD4000, and compared the results. Good correlations were
      found for total nucleated cell count (TNCC), neutrophils, lymphocytes,
      erythroblasts, and the myeloid series to erythroid series (M/E) ratio. It is
      possible to detect blasts that emerge in patients with hematological malignancy
      using the blast flag system installed on the CD4000. Since all of the items can
      be analyzed in about 80 sec with the CD4000, cells in bone marrow aspirates can
      be classified faster with this apparatus than by the microscopic method.
      Therefore, analysis of bone marrow aspirates with this apparatus appears to be
      very useful not only for laboratory testing but also for clinical screening.

PMID- 11948798
TI  - Comparison of ANA endpoint dilution using the PolyTiter immunofluorescent
      titration system and conventional serial dilution.
AB  - The PolyTiter immunofluorescent titration system (PolyTiter system), an
      attachment for conventional fluorescent microscopes, facilitates
      immunofluorescent antinuclear antibody (IFA-ANA) testing by using calibrated
      light attenuation to determine the semiquantitative endpoint dilution or titer of
      ANA-positive specimens. The objective of this study was to compare the
      determination of ANA titer using the PolyTiter system to that of the conventional
      serial dilution method. A total of 172 consecutive ANA-IFA positive serum
      specimens, including the four most common pattern types, were evaluated in
      parallel by two readers to determine the dilution endpoint. The two methods
      produced equal dilution endpoints in 78 specimens (45%), within 1-dilution
      endpoint in 121 specimens (70%), and within 2-dilutions endpoint in 158 specimens
      (92%). The conventional method consistently produced a more conservative dilution
      endpoint than the PolyTiter system for three of the four patterns evaluated
      (i.e., centromere, nucleolar, and speckled vs. homogeneous). The PolyTiter system
      demonstrated satisfactory performance in comparison to the current standard for
      determining ANA dilution endpoints, while significantly reducing operator labor,
      time, and materials usage.

PMID- 11948799
TI  - New compact-type latex photometric immunoassay system for hemoglobin and three
      acute inflammation markers: neutrophil count, C-reactive protein, and anti
      streptolysin O.
AB  - A new compact-type latex photometric immunoassay system, SPOTCHEM IM SI-3510
      (ARKRAY, Inc., Kyoto, Japan), which assays three kinds of inflammatory markers
      neutrophil count (NPC), C-reactive protein (CRP), and anti-streptolysin O (ASO)
      was evaluated. Hemoglobin (Hb), which is a good marker for anemia, can also be
      measured with it. NPC and CRP are measured using antibodies against neutrophilic
      elastase and CRP, purified streptolysin O was used for ASO determination, and Hb
      was measured by an azide-methemoglobin method. Whole blood, serum, and plasma
      specimens can be used as samples with this system. In this study, whole blood
      treated with dipotassium ethylenediamine tetraacetic acid was used for
      evaluation. Linearity and reproducibility were good for all of the items studied.
      Good correlations were observed between the results obtained by this system and
      those obtained by routine methods. Since NPC exhibited a high correlation with
      the routine white blood cell (WBC) counts, it was judged to be useful as a
      substitute for WBC counting. Since this system is small and easy to operate, and
      evaluation revealed reliable results, it was judged to be practical for small
      laboratories, and satellite testing in hospitals and physicians' office
      laboratories for patients suspected to have acute inflammation.

PMID- 11948800
TI  - Specificity of autoantibodies to SS-A/Ro on a transfected and overexpressed human
      60 kDa Ro autoantigen substrate.
AB  - The objective of this study was to analyze apparently discrepant results that
      arose during the use of an indirect immunofluorescence (IIF) assay using
      transfected HEp-2 cells to detect anti-SS-A/Ro autoantibodies in human sera.
      Fourteen sera that had SS-A/Ro antibodies as detected on this commercial
      substrate, but did not have antibodies to SS-A/Ro as determined by double
      immunodiffusion (ID) or enzyme-linked immunosorbent assay (ELISA), were studied
      by immunoprecipitation (IP) of radiolabeled cell extracts and full-length
      recombinant SS-A/Ro. A multi-antigen strip immunoblotting (IB) assay containing
      both the 52- and 60-kDa antigens was included in the analysis. We confirmed that
      12 of 14 of the sera under study had antibodies to SS-A/Ro protein antigens as
      determined by at least one other immunoassay. One serum had antibodies to hyRNA
      but no detectable reactivity with the 52- or 60-kDa antigens. One serum remained
      negative in all assays for SS-A/Ro autoantibodies.

PMID- 11948801
TI  - Portable electrochemical blood uric acid meter.
AB  - We describe a new portable uric acid (UA) meter, called the UASure (Apex
      Biotechnology Corp., Hsinchu, Taiwan). The UASure is an electrochemical blood UA
      meter designed for fast monitoring of UA concentrations in one drop of capillary
      blood using an electrochemical test strip. We compared the UASure with the
      standard method, the Hitachi 7600 modular system (Hitachi, Tokyo, Japan), in 146
      volunteers (average age 62.5 +/- 12.8 years). Of these, 65 were known
      hyperuricemic subjects, 17 of whom received medical therapy. The patients donated
      their capillary and venous blood samples in random order. Capillary blood and one
      drop of venous blood were tested immediately by the UASure. The venous blood in
      the test tube was sent to the central laboratory for serum UA measurement by the
      Hitachi 7600. The intra-assay coefficients of variation (CVs) of the UASure were
      4.79%, 5.77%, and 3.08% at UA levels of 5.8, 7.1, and 13.5 mg/dl, respectively.
      The UA concentrations tested by the UASure correlated well with those by the
      Hitachi 7600 (r = 0.87 in venous sampling and r = 0.78 in capillary sampling, P <
      0.001). The intraclass correlation was good for venous samples by the UASure (rI
      = 0.84, 95% CI 0.82-0.90), somewhat below the meaningful criterion for capillary
      samples by the UASure (rI = 0.77, 95% CI 0.69-0.83). UASure with venous sampling
      is interchangeable with the standard method for UA measurement.

PMID- 11948802
TI  - Analysis of 3-hydroxydodecanedioic acid for studies of fatty acid metabolic
      disorders: preparation of stable isotope standards.
AB  - Current diagnostic tests to detect disorders of fatty acids metabolism, such as
      long-chain hydroxyacyl CoA dehydrogenase deficiency (LCHAD), are hampered by
      insensitivity or a long delay time required for results. Children with LCHAD
      deficiency are known to excrete 3-hydroxydicarboxylic acids with chain lengths of
      10-16 carbons, but a quantitative method to measure excretion of these
      potentially diagnostically important compounds has not been reported. We report
      synthetic schemes for synthesis of 3-hydroxydodecanedioic acid and a di
      deuterated analog, suitable for use in a stable-isotope dilution mass
      spectrometric analytical approach. Evaluation of several common derivatization
      protocols to produce a volatile derivative for gas chromatography determined that
      trimethylsyl derivatives produced the best efficiency and stability. Positive-ion
      chemical ionization mass spectrometry provided the greatest yield of
      characteristic ions. These results indicate the basic reagents needed to develop
      sensitive and accurate 3-hydroxydodecanedioic acid measurements for diagnosis of
      LCHAD deficiency and other fatty acid oxidation disorders.

PMID- 11948803
TI  - Hyaluronate-based extracellular matrix: keeping glia in their place.

PMID- 11948804
TI  - Oxidative stress in glial cultures: detection by DAF-2 fluorescence used as a
      tool to measure peroxynitrite rather than nitric oxide.
AB  - 4,5-diaminofluorescein diacetate (DAF-2DA) is widely used as a fluorescent probe
      to detect endogenously produced nitric oxide (NO). Recent reports that refer to
      the high sensitivity of DAF-2 toward NO prompted us to test its efficiency and
      specificity in a mixed murine primary glial culture model, in which the NO
      synthesizing enzyme inducible nitric oxide synthase (iNOS) is expressed by
      stimulation with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma).
      Cultures were loaded with DAF-2DA and the fluorescence was measured using
      confocal microscopy. NO production in the cultures was determined using the
      ozone/chemiluminescence technique. Due to the extremely high photosensitivity of
      DAF-2, low laser intensities were used to avoid artifacts. No difference in DAF-2
      fluorescence was observed in NO-producing cultures compared to control cultures,
      whereas the NO/peroxynitrite-sensitive dye 2,7-dihydrodichlorofluorescein (DCF)
      showed a significant fluorescence increase specifically in microglia cells. A
      detectable gain in fluorescence was seen when NO-containing buffer was added to
      the DAF-2DA-loaded cells with a minimum NO concentration at 7.7 microM. An
      additional gain of DAF-2 fluorescence was obtained when the cells were depleted
      of glutathione (GSH) with L-buthionine S,R-sulfoximine (BSO). Hence, we monitored
      the change in DAF-2 fluorescence intensity in the presence of NO and O(-*)(2) in
      a cell-free solution. The fluorescence due to NO was indeed larger when O(-*)(2)
      was added, implying a higher sensitivity of DAF-2 for peroxynitrite.
      Nevertheless, our results also indicate that measurement of DCF fluorescence is a
      better tool for monitoring intracellular changes in the levels of NO and/or
      peroxynitrite than DAF-2.

PMID- 11948805
TI  - Expression of glial fibrillary acidic protein and glutamine synthetase by Muller
      cells after optic nerve damage and intravitreal application of brain-derived
      neurotrophic factor.
AB  - Muller glia play an important role in maintaining retinal homeostasis, and brain
      derived neurotrophic factor (BDNF) has proven to be an effective retinal ganglion
      cell (RGC) neuroprotectant following optic nerve injury. The goal of these
      studies was to investigate the relation between optic nerve injury and Muller
      cell activation, and to determine the extent to which BDNF affects the injury
      response of Muller cells. Using immunocytochemistry and Western blot analysis,
      temporal changes in the expression of glial fibrillary acidic protein (GFAP) and
      glutamine synthetase (GS) were examined in rats after optic nerve crush alone, or
      in conjunction with an intravitreal injection of BDNF (5 microg). GFAP protein
      levels were normal at 1 day post-crush, but increased approximately 9-fold by day
      3 and remained elevated over the 2-week period studied. Muller cell GS expression
      remained stable after optic nerve crush, but the protein showed a transient shift
      in its cellular distribution; during the initial 24-h period post-crush the GS
      protein appeared to translocate from the cell body to the inner and outer glial
      processes, and particularly to the basal endfeet located in the ganglion cell
      layer. BDNF alone, or in combination with optic nerve crush, did not have a
      significant effect on the expression of either GFAP or GS compared with the
      normal retina, or after optic nerve crush alone, respectively. The data indicate
      that although BDNF is a potent neuroprotectant in the vertebrate retina, it does
      not appear to have a significant influence on Muller cell expression of either GS
      or GFAP in response to optic nerve injury.

PMID- 11948806
TI  - Immunohistological localization of the myelinating cell-specific receptor LP(A1).
AB  - LP(A1) (also termed Edg-2 or VZG-1) is a G-protein-coupled receptor for
      lysophosphatidic acid and its gene transcripts have been found selectively
      expressed by mature myelin-producing cells. We have raised in rabbit a polyclonal
      antibody against a sequence unique to LP(A1) and common to rat, mouse, and human
      orthologues. In Western blots, LP(A1) immunoreactivity appeared as 44-53 kDa
      bands in extracts from recombinant RH7777 cells expressing LP(A1), mouse purified
      oligodendrocytes, or human white matter, but not from wild-type RH7777 cells or
      purified astrocytes. In glial cultures, LP(A1) immunoreactivity was restricted to
      oligodendrocytes, appeared at cell membrane and processes, colocalized with
      myelin basic protein, and appeared before myelin/oligodendrocyte glycoprotein. In
      slices of rat and human brains, LP(A1) immunoreactivity was found in myelinated
      tracts, as well as in oligodendrocyte somata and their myelinating fibers.
      Immunoreactivities of LP(A1) and myelin basic protein colocalized in the brain,
      but oligodendrocyte soma showed stronger signals for LP(A1) than myelinated
      fibers, whereas the reverse was true for myelin basic protein. These results
      strengthen the view that LP(A1) is involved in myelin formation or maintenance.

PMID- 11948807
TI  - Modifications in astrocyte morphology and calcium signaling induced by a brain
      capillary endothelial cell line.
AB  - Astrocytes extend specialized endfoot processes to perisynaptic and perivascular
      regions, and thus are positioned to mediate the bidirectional flow of metabolic,
      ionic, and other transmissive substances between neurons and the blood stream.
      While mutual structural and functional interactions between neurons and
      astrocytes have been documented, less is known about the interactions between
      astrocytes and cerebrovascular cells. For example, although the ability of
      astrocytes to induce structural and functional changes in endothelial cells is
      established, the reciprocity of brain endothelial cells to induce changes in
      astrocytes is undetermined. This issue is addressed in the present study. Changes
      in primary cultures of neonatal mouse cortical astrocytes were investigated
      following their coculture with mouse brain capillary endothelial (bEnd3) cells.
      The presence of bEnd3 cells altered the morphology of astrocytes by transforming
      them from confluent monolayers into networks of elongated multicellular columns.
      These columns did not occur when either bEnd3 cells or astrocytes were cocultured
      with other cell types, suggesting that astrocytes undergo specific morphological
      consequences when placed in close proximity to brain endothelial cells. In
      addition to these structural changes, the pharmacological profile of astrocytes
      was modified by coculture with bEnd3 cells. Astrocytes in the cocultures showed
      an increased Ca2+ responsiveness to bradykinin and glutamate, but no change in
      responsiveness to ATP, as compared to controls. Coculturing the astrocytes with a
      neuronal cell line resulted in increased responsiveness of the glial responses to
      glutamate but not to bradykinin. These studies indicate that brain endothelial
      cells induce changes in astrocyte morphology and pharmacology.

PMID- 11948808
TI  - L1 expressed by glioma cells promotes adhesion but not migration.
AB  - L1 is an adhesion molecule of the immunoglobulin superfamily expressed by several
      types of cancer, including gliomas. It has been shown that L1 can act as
      chemoattractant to glioma cells, while the effects of L1 expressed by glioma
      cells themselves are unknown to date. We established a C6 rat glioma clone,
      conditionally expressing murine L1 under control of a tetracycline responsive
      promoter. In vitro experiments revealed increased adhesion on matrigel as well as
      increased intercellular adhesion in the presence of L1, whereas no L1-dependent
      effects on proliferation or migration on either matrigel or myelin were observed.
      In vivo experiments using transplantation into nude mouse striatum, where L1
      expression by glioma cells was regulated by tetracycline via drinking water, did
      not show effects of L1 on tumor size or brain invasion. Our data suggest that L1
      expressed on the surface of glioma cells increases cell-matrix and intercellular
      adhesion, but has no apparent effects on proliferation and invasion.

PMID- 11948809
TI  - Modelling large areas of demyelination in the rat reveals the potential and
      possible limitations of transplanted glial cells for remyelination in the CNS.
AB  - Transplantation of myelin-forming glial cells may provide a means of achieving
      remyelination in situations in which endogenous remyelination fails. For this
      type of cell therapy to be successful, cells will have to migrate long distances
      in normal tissue and within areas of demyelination. In this study, 40 Gy of X
      irradiation was used to deplete tissue of endogenous oligodendrocyte progenitors
      (OPCs). By transplanting neonatal OPCs into OPC-depleted tissue, we were able to
      examine the speed with which neonatal OPCs repopulate OPC-depleted tissue. Using
      antibodies to NG-2 proteoglycan and in situ hybridisation to detect platelet
      derived growth factor alpha-receptor Ralpha (PDGFRalpha) mRNA to visualise OPCs,
      we were able to show that neonatal OPCs repopulate OPC-depleted normal tissue 3-5
      times more rapidly than endogenous OPCs. Transplanted neonatal OPCs restore OPC
      densities to near-normal values and when demyelinating lesions were made in
      tissue into which transplanted OPCs had been incorporated 1 month previously, we
      were able to show that the transplanted cells retain a robust ability to
      remyelinate axons after their integration into host tissue. In order to model the
      situation that would exist in a large OPC-depleted area of demyelination such as
      may occur in humans; we depleted tissue of its endogenous OPC population and
      placed focal demyelinating lesions at a distance (< or =1 cm) from a source of
      neonatal OPCs. In this situation, cells would have to repopulate depleted tissue
      in order to reach the area of demyelination. As the repopulation process would
      take time, this model allowed us to examine the consequences of delaying the
      interaction between OPCs and demyelinated axons on remyelination. Using this
      approach, we have obtained data that suggest that delaying the time of the
      interaction between OPCs and demyelinated axons restricts the expression of the
      remyelinating potential of transplanted OPCs.

PMID- 11948810
TI  - Expression of the complement C3a and C5a receptors after permanent focal
      ischemia: An alternative interpretation.
AB  - The receptors for the complement anaphylatoxins C3a and C5a are expressed by
      glial cells and neurons in normal and inflamed brain. Previous studies
      demonstrated modest elevations in mRNA expression of these receptors in a model
      of focal cerebral ischemia. Using a similar model system for both mice and rats,
      we report markedly different patterns of anaphylatoxin receptor mRNA expression
      in cerebral ischemia. C5a receptor expression was dramatically elevated within 3
      h after middle cerebral artery occlusion, while C3aR expression was reduced to
      25% of control animals. By 24 h post-occlusion, expression of both receptors was
      higher than at any other time point examined. This increased expression at late
      time points after occlusion is most likely the result of massive infiltration of
      leukocytes expressing the receptors. We also observed increased receptor mRNA
      expression in sham-operated animals, indicating that the procedures used for
      arterial occlusion affects mechanisms regulating receptor expression. This latter
      result highlights the importance of including this important control group in
      ischemic model systems for proper interpretation of changes in gene expression.

PMID- 11948811
TI  - APP knockout attenuates microglial activation and enhances neuron survival in
      substantia nigra compacta after axotomy.
AB  - Focal microglial activation and progressive dopaminergic neurodegeneration in
      substantia nigra compacta (SNc) have characterized Parkinson's disease (PD). We
      have hypothesized that the microglial response may be provoked by molecular
      signals from chronically stressed SNc neurons. To test whether amyloid precursor
      protein (APP) could serve as such a signal, we evaluated microglial activation in
      SN after unilateral transection of the medial forebrain bundle (MFB) in mice
      either wild-type (WT) or null (KO) for APP. WT and KO mice displayed comparable
      microglial response at the MFB transection site. In WT mice microglial activation
      was first apparent in the ipsilateral SN at 3 days postlesion (dpl), marked by
      morphological change and increased isolectin immunoreactivity. The microglial
      response intensified at 7 dpl and persisted in the medial nigra through 14 dpl.
      In contrast, in KO mice activated microglia appeared predominantly at 7 dpl, with
      little activation at 3 dpl and none at 14 dpl. Neuron number in affected WT SNc
      at 14 dpl was significantly reduced compared with loss in affected KO SNc. The
      delayed and limited local microglial activation and increased neuron survival in
      response to distal axotomy of SNc neurons in APP KO mice are consistent with the
      important role APP in neuronal stress responses in vivo.

PMID- 11948812
TI  - Mass spectrometric fragmentation of cyclic peptides belonging to the polymyxin
      and colistin antibiotics studied by ion trap and quadrupole/orthogonal
      acceleration time-of-flight technology.
AB  - Electrospray ionization linked to quadrupole/orthogonal-acceleration time-of
      flight (Q/oaTOF) and ion trap equipment was used to study the fragmentation
      behavior of the linear side-chain cyclized peptides of the polymyxin B and E
      antibiotics. This study exemplifies both the benefits and the drawbacks of mass
      spectrometric techniques for the determination of the sequence of such complex
      linear side-chain cyclized peptides. Q/oaTOF accurate mass measurements did not
      help sufficiently to assign the product ions observed in the product ion spectra.
      An ion trap mass spectrometer providing MS(n) capability was used to eliminate
      ambiguities encountered with a single MS/MS approach. The complex fragmentation
      behavior of these compounds of well-established structure is described which
      could be useful for structural characterization of unknown substances related to
      polymyxin B and E in the future.

PMID- 11948813
TI  - Characterisation of combinatorial libraries of mucin-2 antigen peptides by high
      resolution mass spectrometry.
AB  - An epitope motif, TX(1)TX(2)T, of mucin-2 glycoprotein was identified by means of
      a mucin-2-specific monoclonal antibody, mAb 994, raised against a synthetic mucin
      derived 15-mer peptide conjugate. For determination of the epitope sequence
      recognised with highest affinity by mAb 994, a combinatorial approach was applied
      using the portioning-mixing technique excluding Cys. Antibody binding of
      libraries was most profound when Gln was at the X(1) position. Analytical
      characterisation of the TQTX(2)T library was conducted by amino acid analysis and
      matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) and
      electrospray ionisation Fourier transform ion cyclotron resonance (ESI-FTICR)
      mass spectrometric methods. Control libraries were prepared by mixing 19
      individual peptides corresponding to the TQTX(2)T sequence. Thus, mixtures of 6,
      10 and 19 pentapeptides were analysed and compared with the combinatorial
      mixture. MALDI-TOFMS was able to detect only partially the components in the 6-
      and 10-member mixtures, but failed to characterise a more complex 19-member
      mixture. In contrast, ESI-FTICRMS resolved all mixtures of higher complexity and
      provided direct identification at monoisotopic resolution, such as for a peptide
      library containing 'isobaric' lysine and glutamine (Delta m = 0.0364 Da). The
      results of this study suggest that ESI-FTICRMS is a powerful tool for
      characterisation of combinatorial peptide libraries of higher complexity.

PMID- 11948814
TI  - Ion trap mass spectrometry in the structural analysis of haemoglobin peptides
      modified by epichlorohydrin and diepoxybutane.
AB  - Ion trap mass spectrometry has been shown to be particularly suitable for the
      structural analysis of high molecular weight peptides directly fragmented in the
      mass analyser without needing further sub-digestion reactions. Here we report the
      advantages of using multi-stage ion trap mass spectrometry in the structural
      characterisation of haemoglobin alkylated with epichlorohydrin and diepoxybutane.
      Alkylated globins were digested with trypsin and the peptide mixtures were
      analysed by MS(3). This technique allows the sequential fragmentation of peptides
      under analysis, giving rise to MS(3) product ion spectra with additional
      information with respect to MS(2) mass spectra. The results obtained complete the
      previously reported structural characterisation of alkylated haemoglobin,
      demonstrating the potential of ion trap mass spectrometry.

PMID- 11948815
TI  - Comparison of gas chromatography and liquid chromatography mass spectrometric
      measurements for high accuracy analysis of cholesterol in human serum by isotope
      dilution mass spectrometry.
AB  - Cholesterol measurements are of vital clinical importance and reliable reference
      materials are essential for method validation. Gas chromatography with mass
      spectrometry (GC/MS) is usually used for the high accuracy analysis of
      cholesterol by isotope dilution. A certified reference material for cholesterol
      content in human serum was analysed by isotope dilution utilising GC/MS and
      liquid chromatography mass spectrometry (LC/MS). The use of LC/MS avoided the
      need for a derivatisation step. Both LC/MS and GC/MS produced results on the
      measurement of cholesterol that agreed within 0.5% of the certified value.
      Moreover, the precision obtained for ratio measurement using both techniques are
      comparable and lead to relative expanded standard uncertainties (with a coverage
      factor of 2) varying between 0.2 and 0.5%.

PMID- 11948816
TI  - Oxygen isotope corrections for online delta(34)S analysis.
AB  - Elemental analyzers have been successfully coupled to stable-isotope-ratio mass
      spectrometers for online measurements of the delta(34)S isotopic composition of
      plants, animals and soils. We found that the online technology for automated
      delta(34)S isotopic determinations did not yield reproducible oxygen isotopic
      compositions in the SO(2) produced, and as a result calculated delta(34)S values
      were often 1-3 per thousand too high versus their correct values, particularly
      for plant and animal samples with high C/S ratio. Here we provide empirical and
      analytical methods for correcting the S isotope values for oxygen isotope
      variations, and further detail a new SO(2)-SiO(2) buffering method that minimizes
      detrimental oxygen isotope variations in SO(2).

PMID- 11948817
TI  - Gas chromatography/mass spectrometric assay of endogenous cellular lipid
      peroxidation products: quantitative analysis of 9- and 10-hydroxystearic acids.
AB  - A sensitive, specific, accurate and reproducible gas chromatography/mass
      spectrometry method was developed for the assay of 9- and 10-hydroxystearic acids
      in samples obtained as cell extracts. The preparation of the samples required
      specific procedures to allow the analysis of both the free and the conjugated
      hydroxy acids as the corresponding methyl esters. The quantification used propyl
      paraben as the internal standard and monitoring of a specific fragment of each
      isomeric hydroxy acid methyl ester, and allowed quantification of the conjugate
      and the free fractions of both 9- and 10-hydroxystearic acids. This method is
      suitable for identification and quantification (LOQ 1.8 and 4.4 ng, respectively)
      of these important metabolites of lipid peroxidation. In particular the
      development of an assay for the free 9-hydroxystearic acid methyl ester makes the
      method a reliable analytical tool for investigations of the role of this
      metabolite in the mechanisms of tumour cell proliferation.

PMID- 11948818
TI  - Determination of paramethoxyamphetamine and other amphetamine-related designer
      drugs by liquid chromatography/sonic spray ionization mass spectrometry.
AB  - Paramethoxyamphetamine (PMA) is an amphetamine-like designer drug that has
      emerged recently on the European illicit drug market. This drug has a wicked
      reputation, as a number of lethal intoxications have occurred. A method using
      high-performance liquid chromatography coupled to ion trap based mass
      spectrometry (LC/MS) is described for the determination of this compound together
      with 3,4-methylenedioxymethamphetamine (XTC or MDMA), amphetamine and 3,4
      methylenedioxyamphetamine (MDA) in human matrices. A liquid/liquid extraction
      (LLE) was applied to whole blood, urine and postmortem tissues. Reversed-phase
      liquid chromatography was performed on a narrow-bore phenyl-type column at a flow
      rate of 0.3 mL/min. A switch box allowed disposal of early-eluting irrelevant
      material to waste, protecting the mass spectrometer from contamination. The
      column effluent was directed into an ion trap mass spectrometer by a sonic spray
      ionization (SSI) interface. The method was validated for all three matrices,
      proving the applicability of SSI even when dealing with complex biological
      matrices. The within-and between-day precisions were less than 17.5% and accuracy
      was below 16.2%. Weighted (1/x) quadratic calibration curves were generated
      ranging from 10 to 1000 ng/mL (blood and urine) or 20 to 2000 ng/g (tissue) and
      correlation coefficients (r(2)) always exceeded 0.995. In addition, the mass
      spectrum of PMA is given together with a proposed fragmentation pattern for the
      obtained LC/MS spectrum. This information can be useful for future identification
      of PMA with LC/MS in biological matrices as well as in confiscated powders or
      tablets.

PMID- 11948819
TI  - Structural analysis of styrene oxide/haemoglobin adducts by mass spectrometry:
      identification of suitable biomarkers for human exposure evaluation.
AB  - The structural characterisation of adducts formed by the in vitro reaction of
      haemoglobin (Hb) with styrene oxide (SO), the most reactive metabolite of the
      industrial reagent styrene, was obtained by liquid chromatography/electrospray
      ionisation mass spectrometry (LC/ES-MS) analysis of modified tryptic peptides of
      human Hb chains. The reactive sites of human Hb towards SO were identified
      through characterisation of alkylated tryptic peptides by matrix-assisted laser
      desorption/ionisation with tandem mass spectrometry (MALDI-MS/MS). A procedure
      was set up based on this characterisation, allowing Hb modification to be
      assessed by monitoring SO/Hb adducts using HPLC with selected ion recording (SIR)
      mass spectrometry. By this methodology it was also possible to compare advantages
      and disadvantages of presently available strategies for the measurement of Hb
      adducts with SO. The results obtained could most plausibly lead to the
      optimisation of molecular dosimetry of SO adducts, and the analytical procedure
      described herein could be applied to the biological monitoring of styrene
      exposure in the workplace.

PMID- 11948820
TI  - (2)H- and (13)C-labelled tracers compared for kinetic studies of ascorbic acid
      metabolism in man: a factor analytical approach.
AB  - A recent report that a (13)C stable isotope method can be used to measure the
      kinetics of ascorbic acid uptake and distribution in man has raised some
      interesting questions with regard to the physiological interpretation of the data
      obtained, in particular the sizes of the ascorbate distribution spaces. In order
      to prove that this result is not a function of the label used we have compared
      the behaviour of two different tracers to see if they are likely to give
      comparable results for the kinetic parameters. Volunteers received an oral dose
      of ascorbic acid, half of which was labelled with (2)H, and half of which was
      labelled with (13)C. Blood samples were taken over the course of the next 48 h,
      and ascorbic acid mass spectra measured by gas chromatography/mass spectrometry
      (GC/MS). Principal component analysis was used to investigate the number of
      factors required to explain the total variations observed in the ratios of the
      molecular isotopomer cluster over the time course of the experiment. Theoretical
      cracking patterns were then used as test vectors in target transformation and as
      the basis for subsequent combination to determine tracer/tracee ratios. Two
      factors were found sufficient to account for the observed cracking pattern
      variations within experimental error. These were identified as (1) the spectrum
      of unlabelled (endogenous) ascorbic acid, and (2) a linear combination of the
      spectra of the two labelled species used. The absence of a third factor in the
      decomposition indicates that there is no difference in the behaviour of the (13)C
      and (2)H-labelled tracers. Target testing allowed the tracer/tracee ratios to be
      determined using calculated cracking patterns, and produced equivalent results to
      conventional methods. Our experience in this work indicates that factor analysis
      has a useful place in many kinetic studies of this kind, either with one or many
      labelled species.

PMID- 11948821
TI  - Side-chain radical losses from radical cations allows distinction of leucine and
      isoleucine residues in the isomeric peptides Gly-XXX-Arg.
AB  - Sequencing of peptides via low-energy collision-induced dissociation of
      protonated peptides typically yields b(n) and y(n) sequence ions. The isomeric
      residues leucine and isoleucine rarely can be distinguished in these experiments
      since they give b(n) and y(n) sequence ions of the same m/z. Siu's pioneering
      work on electrospray ionization of copper complexes of peptides (Chu IK,
      Rodriquez CF, Lau TC, Hopkinson AC, Siu KWM. J. Phys. Chem. B 2000; 104: 3393)
      provides a way of forming radical cations of peptides in the gas phase. This
      method was used to generate M(+ small middle dot) ions of the two isomeric
      peptides Gly-Leu-Arg and Gly-Ile-Arg in order to compare their fragmentation
      reactions. Both radical cations fragment to give even electron y(2) and y(1)
      sequence ions as well as side-chain radical losses of CH(3) and CH(3)CH(2) for
      isoleucine and (CH(3))(2)CH for leucine. In contrast the [M + H](+) and [M +
      2H](2+) ions do not allow distinction between the isomeric leucine and isoleucine
      peptides.

PMID- 11948822
TI  - Determination of (13)C natural abundance of amino acid enantiomers in soil:
      methodological considerations and first results.
AB  - The application of a combined gas chromatography-combustion/isotope ratio mass
      spectrometry (GC-C/IRMS) method for stable carbon isotope analysis of amino acid
      enantiomers in soil samples is presented. Triplicate delta(13)C analyses of
      pentafluoropropionyl (PFP) isopropyl ester derivatives of 27 amino acid
      enantiomers revealed that discrimination of (13)C during derivatization is
      different for different amino acid enantiomers and different amounts. Injection
      of increasing amounts of amino acid derivatives showed that the isotopic signal
      varied up to 10 per thousand for D-aspartic acid. Correction for the delta(13)C
      signal of underivatized amino acid enantiomers is possible for all investigated
      amino acid enantiomers using logarithmic functions. Operating the GC-C/IRMS
      system in the split-mode (split ratio 1:12) is possible but resulted in a higher
      isotopic discrimination. The detection limit approached 3 ng for some amino acid
      enantiomers in the splitless mode, while the lower limit of routine determination
      exceeded 10 ng injection amount. The upper limit at which accurate stable isotope
      values were obtained was 200 ng injection amount. Compound-specific delta(13)C
      analysis of alanine, valine, aspartic and glutamic acid showed that the D-forms
      were enriched in (13)C relative to the L-forms, suggesting that microbes
      significantly contributed to the formation of the D-enantiomers in soil.

PMID- 11948823
TI  - One-way hydrophobic surface foil for UV matrix-assisted laser
      desorption/ionization mass spectrometry of peptides.

PMID- 11948824
TI  - Quantification of errors in volume measurements of the caudate nucleus using
      magnetic resonance imaging.
AB  - PURPOSE: To quantify the various sources of error in measuring the volume of the
      caudate nucleus and to understand these errors would lead to the standardization
      of the MRI protocol and would make the utility of data from around the world more
      viable in a global database. MATERIALS AND METHODS: We collected data at four
      different sites all using a Siemens 1.5T Vision MR Scanner. In all cases the same
      3D gradient-echo scans were used on a single volunteer and analyzed by a set of
      five observers. RESULTS: The errors estimated were: system calibration (a random
      variation of up to 1.2%), partial volume error (a bias of up to 1.5% using
      isotropic resolution of 1 x 1 x 1 mm(3)), geometric distortion (a potential bias
      of 1%), intra-observer error (a random variation of up to 3%), effects of ringing
      (area biases of up to 7% when a zoom of 4 was used) and inter-observer error
      (with a bias of usually 5- 10% but sometimes as large as 16% among our five
      observers). Individual mean variations from one system to another differed by
      less than 5% (except for two observers at one site), consistent with a maximum
      error of 7% coming from the area bias due to limitations in the images
      themselves. We also measured the effect of variable resolution on the volume
      estimates and found that the measured volumes were consistent over a broad range
      of signal-to-noise-ratios (SNRs). CONCLUSION: Given the observed dependence of
      the caudate volumes on SNR and resolution, if isotropic resolution is required
      because a complicated structure is being imaged, then the lower SNR suffered by
      collecting 1 x 1 x 1 mm(3) data at 1.5T still appears to be sufficient to make
      accurate volume measurements as long as the contrast-to-noise ratio (CNR) is on
      the order of 4:1. Based on our results, predictions are made as to what the best
      approach would be to improve the data acquisition scheme to keep individual
      errors under 2% and biases under 3.5%. We conclude that if users can be trained
      to identify the structure of interest in the same way, the inter-observer error
      could be reduced to that of intra-observer day-to-day error.

PMID- 11948825
TI  - Diffusion-weighted imaging of the spinal cord: interleaved echo-planar imaging is
      superior to fast spin-echo.
AB  - PURPOSE: To compare and evaluate two novel diffusion-weighted sequences, based
      either on fast spin-echo (FSE) or interleaved echo-planar imaging (EPI) methods,
      as potential tools for investing spinal cord abnormalities. MATERIALS AND
      METHODS: Following recent improvements, both interleaved EPI (IEPI) and FSE
      techniques could be alternative approaches for rapid diffusion-weighted imaging
      (DWI). Therefore, a navigated diffusion-weighted multishot FSE sequence and a fat
      suppressed navigated diffusion-weighted IEPI sequence with local shimming
      capabilities were tested. Both methods were compared in a consecutive series of
      five healthy volunteers and five patients with suspected intramedullary lesions.
      The sequences were graded qualitatively as either superior, inferior, or equal in
      quality, and also quantitatively by measuring the amount of ghosting artifacts in
      the background. Quantitative measurements of the diffusion coefficients within
      the spine were included. RESULTS: The overall image quality of IEPI was superior
      to FSE. Two out of five FSE scans were rated with poor image quality, whereas all
      IEPI scans were of sufficient quality. The ghosting levels ranged from
      approximately 3.3% to 6.2% for IEPI and from approximately 7.5% to 18.9% for FSE.
      Diffusion coefficients measured in healthy volunteers were similar for both IEPI
      and FSE, but showed higher fluctuations with the FSE technique. CONCLUSION:
      Despite potential advantages of FSE, the IEPI technique is preferable for DWI
      applications in the spinal cord.

PMID- 11948826
TI  - MR-guided percutaneous core biopsy of small breast lesions: first experience with
      a vertically open 0.5T scanner.
AB  - PURPOSE: The growing use of highly sensitive but only moderate specific breast
      MRI requires the development of both minimal-invasive as well as precise biopsy
      systems. The aim of the study was to prove the accuracy and feasibility of a
      biopsy procedure carried out in prone position in a vertically opened MR imager.
      MATERIALS AND METHODS: The biopsies were carried out in 21 women with lesions
      visible on MRI alone using an open breast coil with an integrated biopsy device.
      A 14 G coaxial needle was placed under near real-time MRI-guidance. After the tip
      of this needle was verified in contact with the lesion, we used a non MR
      compatible, but MR-safe biopsy gun with a 16 G canula to take four to eight
      cores. RESULTS: We found eight malignant and 12 benign lesions. In one patient
      the procedure was not successful. In case of malignancy, the operation confirmed
      the diagnosis in all cases. The 12/21 patients with benign lesions have been
      followed without evidence of lesions growth over eight to 28 months. CONCLUSION:
      The described procedure allows MRI-guided minimal invasive core biopsy of small
      breast lesions (five to 17 mm) with a high degree of accuracy.

PMID- 11948827
TI  - Perfusion abnormalities in pulmonary embolism studied with perfusion MRI and
      ventilation-perfusion scintigraphy: an intra-modality and inter-modality
      agreement study.
AB  - PURPOSE: To compare perfusion magnetic resonance imaging (MRI) and ventilation
      perfusion scintigraphy (V-P scan) in the study of perfusion abnormalities in
      pulmonary embolism (PE) and to compare the PE results to the findings previously
      reported for pneumonia and chronic obstructive pulmonary disease (COPD), in terms
      of perfusion abnormalities. MATERIALS AND METHODS: Dynamic contrast-enhanced MR
      images and V-P scans of 20 patients with PE, 11 patients with acute pneumonia,
      and 13 patients with exacerbation of COPD were studied. Five categories of
      perfusion abnormalities within each imaging modality were defined. Intra- and
      inter-modality agreement (kappa values) in the evaluation of perfusion
      abnormalities were calculated, based on the two observers of each imaging
      modality (all blinded to each other and true diagnosis). Finally, three
      categories of perfusion MRI diagnosis (PE, pneumonia, and COPD) were also defined
      and the inter-observer agreement (kappa value) was calculated. RESULTS: For PE,
      the intra-modality agreement (kappa value) in the evaluation of perfusion
      abnormalities was 0.77 for MRI and 0.65 for V-P scan. The inter-modality
      agreement varied from 0.52 to 0.57, respectively, and was observer-dependent. For
      the pooled group of PE, pneumonia, and COPD, the intra-modality agreement of
      perfusion abnormalities was 0.76 for MRI and 0.65 for V-P scan, and the inter
      modality agreement varied from 0.51 to 0.56. The kappa value for inter-observer
      agreement for MRI diagnosis was 0.92. CONCLUSION: Evaluation of perfusion
      abnormalities in PE, pneumonia, and COPD using perfusion MRI and V-P scan showed
      a high intra-modality agreement that was higher than the inter-modality
      agreement. Further studies are now needed in patients presenting with possible PE
      to evaluate the sensitivity and specificity of the method.

PMID- 11948828
TI  - Evaluation of iron overload by single voxel MRS measurement of liver T2.
AB  - PURPOSE: To overcome the difficulty of poor signal-to-noise ratio of magnetic
      resonance imaging (MRI) in evaluating heavy iron overload by using a single voxel
      magnetic resonance spectroscopy (MRS) technique. MATERIALS AND METHODS: A single
      voxel STEAM pulse sequence with a minimum TE of 1.5 msec and a sampling volume of
      36.6 cm(3) was developed and applied to 1/T2 measurement of the liver in 14
      patients with thalassemia whose liver iron concentration was determined through
      biopsy. RESULTS: The iron level ranged from 0.23 to 37.15 mg Fe/g dry tissue with
      a median value of 18.06. In all cases, strong MR signals were obtained. 1/T2 was
      strongly correlated with the liver iron concentration (r = 0.95, P < 0.00005).
      CONCLUSION: The single voxel MRS measurement of T2 in liver iron overload
      overcomes the difficulty of lack of detectable signals in conventional MRI when
      the iron level is high. There is an excellent correlation between the iron level
      and 1/T2.

PMID- 11948829
TI  - Small bowel MRI: comparison of a polyethylene glycol preparation and water as
      oral contrast media.
AB  - PURPOSE: To compare water and a polyethylene glycol (PEG) preparation as
      potential oral contrast media for magnetic resonance imaging (MRI) of the small
      bowel. MATERIALS AND METHODS: Twenty-two healthy volunteers underwent separate
      MRI examinations after drinking up to two liters of water or PEG preparation.
      Small bowel images were obtained every 10 minutes for at least two hours using
      breath-hold single shot half-Fourier imaging, including both thick section
      projection and thin section images. Examinations were evaluated by two
      radiologists in consensus, blinded to the volunteer and contrast details, for
      arrival at the terminal ileum, transit time, and demonstration of small bowel
      segments. RESULTS: The PEG preparation was significantly better than water at
      reaching the terminal ileum (PEG 21/22 volunteers [95.45%], water 14/22
      volunteers [63.6%], P = 0.04). There was no significant difference in the mean
      transit time (water 51 +/- 48 minutes, PEG 37.7 +/- 22 minutes) or in the
      demonstration of the stomach, duodenum, and jejunum, but the PEG preparation was
      significantly better at demonstrating the ileum (P = 0.005) and terminal ileum (P
      = 0.002). CONCLUSION: A PEG preparation is significantly better than water as an
      oral contrast medium for demonstrating the distal small bowel during breath-hold
      T2-weighted MRI.

PMID- 11948830
TI  - MRI-guided thermal therapy of transplanted tumors in the canine prostate using a
      directional transurethral ultrasound applicator.
AB  - PURPOSE: To evaluate MRI-based techniques for visual guidance, thermal
      monitoring, and assessment during transurethral ultrasound thermal therapy of
      implanted tumors in an in vivo canine prostate model. MATERIALS AND METHODS:
      Transmissible venereal tumors (TVT) were grown in the right lobe of the prostate
      in four dogs. High-temperature thermal therapy was selectively applied to the
      tumor-bearing lobe using a transurethral ultrasound applicator with a 180 degrees
      directional heating pattern. Temperature-sensitive MRI (MRTI) using a fast
      interleaved gradient-echo echo-planar (iGE-EPI) imaging sequence was used for
      cumulative thermal dose calculations in multiple image planes during the
      treatment. The results from MRTI-based dose maps and post-treatment MRI were
      compared to those from histologic analysis. RESULTS: MRTI monitoring in multiple
      planes across the prostate guided the use and control of a directive ultrasound
      applicator for the selective ablation of the sections of the prostate that
      contained implanted tumors. Findings in gadolinium enhanced MRI obtained
      immediately after thermal therapy slightly underestimated the size of tissue
      necrosis after treatment, as verified by histopathologic analysis. CONCLUSION:
      The use of multiplanar MRTI with a transurethral ultrasound applicator shows
      significant potential for selective thermal ablation of prostate tumor and
      tissue.

PMID- 11948831
TI  - Measurement of vessel wall strain using cine phase contrast MRI.
AB  - PURPOSE: To determine the feasibility of using magnetic resonance imaging (MRI)
      to non-invasively measure strain in the aortic wall. MATERIALS AND METHODS: Cine
      phase contrast MRI was used to measure the velocity of the aortic wall and
      calculate changes in circumferential strain over the cardiac cycle. A deformable
      vessel phantom was used for initial testing and in vitro validation. Ultrasonic
      sonomicrometer crystals were attached to the vessel wall and used as a gold
      standard. RESULTS: In the in vitro validation, MRI-calculated wall displacements
      were within 0.02 mm of the sonomicrometer measurements when maximal displacement
      was 0.28 mm. The measured maximum strain in vitro was 0.02. The in vivo results
      were on the same order as prior results using ultrasound echo-tracking.
      CONCLUSION: Results of in vivo studies and measurement of cyclic strain in human
      thoracic and abdominal aortas demonstrate the feasibility of the technique.

PMID- 11948832
TI  - MRA of the lower extremities in patients with pulmonary embolism using a blood
      pool contrast agent: initial experience.
AB  - PURPOSE: To evaluate the feasibility of blood pool contrast-enhanced magnetic
      resonance angiography (MRA) to visualize the arterial and venous vessel tree and
      to detect deep venous thrombosis (DVT) of the lower extremities. MATERIALS AND
      METHODS: Nine consecutive patients with pulmonary embolism (mean age = 46 +/- 9)
      were randomized to various doses of NC100150 (between 0.75 and 6 mg of Fe/kg of
      body weight). A T1-weighted (T1W) 3D gradient recalled echo (GRE) sequence (TE =
      2.0 msec, TR = 5.0 msec) was used. Two observers blinded to the dose of contrast
      agent assessed image quality, contrast attenuation, and appearance of thrombi.
      RESULTS: Qualitative assessment of overall MRA image quality and semiquantitative
      vessel scoring revealed good to excellent delineation of venous and arterial
      vessel segments independent of the dose of NC100150. However, quantitative region
      of interest analysis revealed a significantly higher signal-to-noise ratio (SNR)
      in the high-dose group than in the mid- and low-dose groups of NC100150 (P <
      0.01). Between dose groups, the SNR was independent of vessel type (artery or
      vein) and vessel segment localization (proximal or distal). All seven venous
      thrombi (mean length = 7.2 +/- 0.95 cm) were characterized by a very low signal
      intensity (SI), which was only 16.6 +/- 7% of the SI in adjacent venous segments
      (P < 0.0001). CONCLUSION: High-quality MR angiograms of the lower extremities can
      be obtained using low concentrations of NC100150 in combination with a strong T1W
      3D GRE sequence. The obvious delineation of venous thrombi suggests that this
      technique may be potentially used as a noninvasive "one-stop shopping" tool in
      the evaluation of thromboembolic disease.

PMID- 11948833
TI  - Segmentation with gray-scale connectedness can separate arteries and veins in
      MRA.
AB  - PURPOSE: To describe and present some preliminary results for a novel algorithm
      for segmentation with gray-scale connectedness as a means to separate arteries
      and veins in magnetic resonance angiography (MRA). MATERIALS AND METHODS: The
      proposed algorithm, SeparaSeed, uses the gray-scale degree of connectedness as a
      tool to find the zone surrounding each vessel, in order to split the original
      volume into its different vessel components. In contrast to traditional
      segmentation methods, no gray-scale information is lost in the process. The
      segmentation is performed in one step, resulting in a partition of the initial
      volume into a chosen number of regions of interest (ROIs). Finally, visualization
      is achieved by projecting the 3D vessel trees to 2D using the common maximum
      intensity projection (MIP). The algorithm was tested in two MRA data sets of the
      vessels of the pelvis acquired after injection of an intravascular contrast agent
      and in one data set of the vessels of the neck with gadolinium. RESULTS: In all
      data sets, a large proportion of the venous signal was removed while preserving
      that of the arteries, thus improving visualization of the relevant vessels.
      CONCLUSION: Separation of arteries and veins is feasible with the proposed
      algorithm with a moderate amount of interaction.

PMID- 11948834
TI  - The OptiMARK clinical development program: summary of safety data.
AB  - PURPOSE: To describe and summarize the safety data from the OptiMARK clinical
      development program. MATERIALS AND METHODS: In the 18 clinical studies comprising
      the clinical program, doses ranging from 0.1 to 0.7 mmol/kg were administered to
      healthy adult volunteers, patients with hepatic or renal impairment, and patients
      with confirmed or highly suspected central nervous system (CNS), liver, breast,
      vascular, bone, or soft tissue pathologies. A total of 2038 injections of
      OptiMARK, Magnevist, or placebo were administered to 1684 subjects. Safety
      assessments were performed at appropriate intervals during all Phase 1, 2, and 3
      studies. RESULTS: Of the 1684 subjects exposed to a study drug or placebo in the
      clinical development program, 646 subjects experienced 1293 adverse events.
      Thirty-one percent of the OptiMARK injections were associated with an adverse
      event. In comparison, 35% of Magnevist injections and 48% of placebo injections
      were associated with at least one adverse event. CONCLUSIONS: OptiMARK was safe
      and well-tolerated with a safety profile similar to that of Magnevist.

PMID- 11948835
TI  - SMART-PET: multimodality white matter imaging and display without loss of
      quantitative information.
AB  - PURPOSE: To improve analysis of cerebral white matter (WM) in fluoro-deoxy
      glucose positron emission tomography (PET) images. MATERIALS AND METHODS: A
      multimodality analysis technique (segmented MRI and registered Talairach
      transformed PET [SMART-PET]) was used for quantitative assessment of WM
      metabolism. Data processing included Talairach transformation of three
      dimensional magnetic resonance imaging (MRI) and subsequent automated
      segmentation and coregistration to normalized PET images. Color model
      transformations were used for combined display: the hue saturation value color
      model was regarded as a three-dimensional data matrix, integrating quantitative
      voxel data of both modalities. The technique was applied in normal subjects and
      in patients suffering from different WM diseases. Regional analysis was performed
      to classify metabolic impairment on a five-point scale. RESULTS: Using SMART-PET,
      a considerable gain in image contrast for WM was achieved in all cases. In the
      normal subjects, WM metabolism was shown to be homogeneously unimpaired. Sum
      scores of regional analysis revealed metabolic WM changes in all patients. Extent
      of WM hypometabolism exceeded the extent of the lesions as delineated by MRI
      signal changes. CONCLUSION: The potential of the method for further elucidation
      of the role of WM diseases in brain dysfunction in patients is discussed.

PMID- 11948836
TI  - Comparison of fat suppression strategies in 3D spiral coronary magnetic resonance
      angiography.
AB  - PURPOSE: In the present study, the impact of the two different fat suppression
      techniques was investigated for free breathing 3D spiral coronary magnetic
      resonance angiography (MRA). As the coronary arteries are embedded in epicardial
      fat and are adjacent to myocardial tissue, magnetization preparation such as T(2)
      preparation and fat suppression is essential for coronary discrimination.
      MATERIALS AND METHODS: Fat-signal suppression in three-dimensional (3D) thin-
      slab coronary MRA based on a spiral k-space data acquisition can either be
      achieved by signal pre-saturation using a spectrally selective inversion recovery
      pre-pulse or by spectral-spatial excitation. In the present study, the
      performance of the two different approaches was studied in healthy subjects.
      RESULTS: No significant objective or subjective difference was found between the
      two fat suppression approaches. CONCLUSION: Spectral pre-saturation seems
      preferred for coronary MRA applications due to the ease of implementation and the
      shorter cardiac acquisition window.

PMID- 11948837
TI  - Fast imaging of phosphocreatine in the normal human myocardium using a three
      dimensional RARE pulse sequence at 4 Tesla.
AB  - PURPOSE: To investigate the use of a three-dimensional rapid acquisition with
      relaxation enhancement (RARE) pulse sequence for direct acquisition of
      phosphocreatine (PCr) images of the human myocardium. MATERIALS AND METHODS: A
      short elliptical birdcage radiofrequency (RF) body coil was constructed to
      produce a uniform flip angle throughout the chest cavity. In vivo images using a
      spectrally-selective RARE sequence with a spatial resolution of 1.2 cm x 1.2 cm x
      2.5 cm (4 cm(3)) were acquired in nine minutes and 40 seconds. RESULTS: Scans of
      phantoms demonstrated excellent spectral selectivity. The signal-to-noise ratio
      in the myocardium ranged from 12.6 in the anterior wall to 5.3 in the mid septum.
      CONCLUSION: This study demonstrates that PCr data can be acquired using a three
      dimensional RARE sequence with greater spatial and temporal resolution than
      spectroscopic techniques.

PMID- 11948839
TI  - Application of magnetization transfer at 3.0 T in three-dimensional time-of
      flight magnetic resonance angiography of the intracranial arteries.
AB  - PURPOSE: To apply magnetization transfer (MT) at 3.0 T in three-dimensional time
      of-flight magnetic resonance angiography of the intracranial arteries. MATERIALS
      AND METHODS: This study was performed on phantoms and seven volunteers to
      determine the effects of MT at 3.0 T. By using a modulated MT approach and an
      altered phase encode order, the specific absorption rate (SAR) was kept below 3
      W/kg over any 8-second time period. RESULTS: For a 20-degree flip angle and 36
      msec repetition time, the background suppression at 3.0 T was improved with MT by
      52 +/- 5% for white matter and 40 +/- 8% for grey matter, making the distal
      intracranial vasculature significantly more discernible. CONCLUSIONS: MT at 3.0 T
      can significantly improve background suppression in 3D time-of-flight magnetic
      resonance angiography (MRA) of the intracranial arteries without exceeding SAR
      guidelines.

PMID- 11948838
TI  - Breath-hold three-dimensional true-FISP imaging of coronary arteries using
      asymmetric sampling.
AB  - PURPOSE: To evaluate the feasibility of using asymmetric sampling in a three
      dimensional, magnetization-prepared, segmented true-FISP (fast imaging with
      steady-state precession) sequence in order to reduce the sensitivity to resonance
      offsets, while simultaneously improving imaging speed. MATERIALS AND METHODS:
      Asymmetric sampling reduces the repetition time, leading to reduced resonance
      offset effects and improved resolution in a fixed imaging time. However, it
      introduces additional phase terms due to blood flow, which can cause image
      artifacts. Computer simulations were performed to study the off-resonance and
      flow effects of asymmetric sampling in true-FISP. Coronary artery imaging was
      performed in healthy volunteers. RESULTS: Simulations and volunteer studies show
      that image artifacts due to flow-induced phase variations may be acceptable at
      low velocities. Volunteer studies demonstrate that relatively high-resolution
      coronary artery images can then be acquired within a single breath-hold with
      segmented three-dimensional true-FISP imaging using data asymmetry in the readout
      direction. CONCLUSION: Asymmetric sampling is a useful modification to true-FISP
      for reducing the off-resonance artifacts and improving imaging speed when the
      flow velocities are small.

PMID- 11948840
TI  - Utilizing SENSE to achieve lower station sub-millimeter isotropic resolution and
      minimal venous enhancement in peripheral MR angiography.
AB  - PURPOSE: To use the parallel imaging technique, sensitivity encoding (SENSE), to
      increase spatial resolution and decrease venous contamination in peripheral
      magnetic resonance angiography (MRA). MATERIALS AND METHODS: Moving table, single
      bolus peripheral contrast-enhanced (CE) -MRA was performed on nine patients.
      Manual table movement combined with SENSE in the upper station allowed for more
      rapid overall scan coverage such that acquisition of the lower station began 34
      seconds after aortic contrast arrival. True sub- millimeter isotropic resolution
      was achieved in the lower station. RESULTS: Diagnostic MR angiograms of all three
      stations were obtained in all nine patients. Venous enhancement did not confound
      interpretation in any case. Sub-millimeter lower station resolution provided
      excellent vascular detail. CONCLUSION: Decreased delay time between upper and
      lower station acquisition in single bolus peripheral MR angiograms, now possible
      using parallel imaging techniques, combined with lower station sub-millimeter
      resolution may decrease venous contamination and increase overall
      interpretability, thus increasing clinical acceptance of peripheral MRA.

PMID- 11948841
TI  - Pelvic lymph node visualization with MR imaging using local administration of
      ultra-small superparamagnetic iron oxide contrast.
AB  - PURPOSE: To determine if interstitial injection of iron oxide particles improves
      visualization of pelvic lymph nodes at magnetic resonance imaging (MRI) and to
      determine the effect of injection site on location of visualized nodes. MATERIALS
      AND METHODS: In nine healthy volunteers, ferumoxtran-10 iron oxide (0.28 mg iron
      per kg) was injected into the anterior thigh (three subjects) or perianal (three
      subjects) or periprostatic tissues (three subjects). MRI at 1.5 T was performed
      before injection and one, three, and seven days after injection. RESULTS: The
      mean of 30 nodes seen post-injection was greater than the mean of 5.8 seen pre
      injection (P < 0.001). After thigh injection, a mean of three internal vs. 36
      external nodes were seen. Compared with thigh injection, there was a higher
      fraction of internal nodes with perianal (mean of nine internal vs. 14 external,
      P < 0.001) and periprostatic injection (mean of 11 internal vs. five external, P
      < 0.001). More nodes were seen with gradient-echo sequences than with other
      sequences (P < 0.001). CONCLUSION: Interstitial injection of iron oxide particles
      increases visualization of pelvic lymph nodes. Perianal and periprostatic
      injection increases the number of internal pelvic lymph nodes seen compared with
      thigh injection.

PMID- 11948842
TI  - Accurate mass measurement of DNA oligonucleotide ions using high-resolution time
      of-flight mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization
      (ESI) time-of-flight mass spectrometry (TOFMS) play an essential role in the
      analysis of biological molecules, not only peptides and proteins, but also DNA
      and RNA. Tandem mass spectrometry used for sequence analysis has been a major
      focus of technological developments in mass spectrometry, but accurate mass
      measurements by high-resolution TOFMS are equally important. This paper describes
      the role that high mass measurement accuracy can play in DNA composition
      assignment and discusses the influence of several parameters on mass measurement
      accuracy in both MALDI and ESI mass spectra. Five oligonucleotides (5-13mers)
      were used to test the resolving power and mass measurement accuracy obtained with
      MALDI and ESI instruments with reflectron TOF mass analyzers. The results from
      the experimental studies and additional theoretical calculations provide a basis
      to predict the practical utility of high-resolution TOFMS for the analysis of
      larger oligonucleotides.

PMID- 11948843
TI  - Investigation of ion-pair precipitates of selected alkoxylates and complex salts
      of specific metal cations by liquid secondary ion mass spectrometry.
AB  - Liquid secondary ion (LSI) mass spectra of ion-pair precipitates obtained for
      Triton X-100 with strontium, lead, cadmium and mercury tetraphenylborates and for
      selected butoxylene-ethoxylene monoalkyl ethers with barium
      tetraiodobismuthate(III) are discussed. On the basis of LSI mass spectra,
      recorded in both positive and negative modes, the formulae of the ion-pair
      precipitates were determined. On the basis of B/E mass spectra, the fragmentation
      routes of [M - H + Ba](+) ions for butoxylene-ethoxylene monoalkyl ether
      complexes of barium and [M - H + Cd](+) ions for the Triton X-100 complex of
      cadmium are proposed.

PMID- 11948844
TI  - Structural characterization of hexoses and pentoses using lead cationization. An
      electrospray ionization and tandem mass spectrometric study.
AB  - The analytical potential of the complexation of isomeric underivatized hexoses (D
      glucose, D-galactose, D-mannose, D-talose, D-fructose), methylglycosides (1-O
      methyl-alpha-D-glucose and 1-O-methyl-beta-D-glucose) and pentoses (D-ribose, D
      xylose, D-arabinose and D-lyxose) by Pb(2+) ions, was investigated by
      electrospray ionization and tandem mass spectrometry (MS/MS). Pb(2+) ions react
      mainly with monosaccharides by proton abstraction to generate
      [Pb(monosaccharide)(m) - H](+) ions (m = 1-3). At low cone voltage, a less
      abundant series of doubly charged ions of general formula
      [Pb(monosaccharide)(n)](2+) is also observed. The maximum number n of
      monosaccharides surrounding a single Pb(2+) ion depends on the metal :
      monosaccharide ratio. Our study shows that MS/MS experiments have to be performed
      to differentiate Pb(2+)-coordinated monosaccharides. Upon collision,
      [Pb(monosaccharide) - H](+) species mainly dissociate according to cross-ring
      cleavages, leading to the elimination of C(n)H(2n)O(n) neutrals. The various
      fragmentation processes observed allow the C(1), C(2) and C(4) stereocenters of
      aldohexoses to be characterized, and also a clear distinction aldoses and
      fructose. Furthermore, careful analysis of tandem mass spectra also leads to
      successful aldopentose distinction. Lead cationization combined with MS/MS
      therefore appears particularly useful to identify underivatized monosaccharides.

PMID- 11948845
TI  - Fragmentation characteristics of peptide-metal ion adducts under matrix-assisted
      laser desorption/ionization post-source decay time-of-flight mass spectrometric
      conditions.
AB  - Fragmentation reactions of sodium-cationized enkephalin peptides generated by
      matrix-assisted laser desorption/ionization were studied using post-source decay
      (PSD) with a reflectron time-of-flight mass spectrometer. Several matrices and
      analyte-matrix sample preparation methods were evaluated for high-intensity ion
      currents that could last for the entire PSD analysis. A triple dried-droplet
      sample preparation procedure with 2,5-dihydroxybenzoic acid as the matrix was
      found to yield abundant longer-lasting ion signals of the peptide-Na(+) ion
      adducts. The principal decay product of these adduct ions is the [b(n-1) + Na +
      OH](+) ion, which provides an unambiguous identification of the C-terminal
      residue of a peptide. In some peptides, the loss of a second residue from the C
      terminus is also observed. No other sequence-specific ions were observed.

PMID- 11948846
TI  - Quantitative gas chromatographic/mass spectrometric analysis of morphine
      glucuronides in human plasma by negative ion chemical ionization mass
      spectrometry.
AB  - A sensitive and specific method for the determination of morphine glucuronides in
      human plasma is presented. Morphine glucuronides, namely morphine-6-glucuronide
      (M6G) and morphine-3-glucuronide (M3G), were extracted from plasma by solid-phase
      extraction on C(18) cartridges at pH 9.3 and derivatized to their
      pentafluorobenzyl ester trimethylsilyl ether derivatives. The compounds were
      measured by gas chromatography/negative ion chemical ionization mass spectrometry
      without any further purification. Using this detection mode, a diagnostic useful
      fragment ion at m/z 748 was obtained at high relative abundance for both target
      compounds. [(2)H(3)]-labeled morphine glucuronides were used as internal
      standards. Calibration graphs were calculated by polynomial fit within a range of
      10-1280 and 15-1920 nmol l(-1) for the 6- and 3-glucuronide, respectively. At the
      limit of quantitation (LOQ), the inter-assay precision was 2.21% (M3G) and 2.23%
      (M6G) and the GC/MS assay variability was 1.8% (M3G) and 0.9% (M6G). The accuracy
      at the LOQ showed deviations of +4.92% (M3G) and +1.5% (M6G). The sample recovery
      after solid-phase extraction was 84.7% for both M3G and M6G. The method is
      rugged, rapid and robust and has been applied to the batch analysis of morphine
      glucuronides during pharmacokinetic profiling of the drugs.

PMID- 11948848
TI  - Identification of glucuronide conjugates of ketobemidone and its phase I
      metabolites in human urine utilizing accurate mass and tandem time-of-flight mass
      spectrometry.
AB  - The glucuronide conjugates of ketobemidone, norketobemidone and
      hydroxymethoxyketobemidone were identified in human urine post-intravenous
      administration of Ketogan Novum. The human urine was extracted on a mixed-mode
      solid-phase micro-column before analysis with liquid chromatography/electrospray
      ionization time-of-flight mass spectrometry (LC/ESI-TOF-MS) and tandem MS
      (MS/MS). Accurate mass and collision-induced dissociation product ion spectra
      were used for identification of the glucuronide conjugates. Two different TOF
      mass spectrometers were used and the accurate mass measurements were performed on
      three separate days with each instrument. The accuracy of the mass measurements
      was better than 2.1 ppm for two out of three conjugates and the inter-day
      relative standard deviation was within +/-0.00049%. The MS/MS fragmentation
      patterns of the conjugates were in accordance with those of the synthetic
      aglycones and included peaks originating from the [M + H](+) ion of the
      respective aglycone.

PMID- 11948847
TI  - Influence of a ring substituent on the tendency to form H(2)O adducts to Ag(+)
      complexes with phenylalanine analogues in an ion trap mass spectrometer.
AB  - In a previous report we showed that certain binary Ag(+)-amino acid complexes
      formed adduct ions by the attachment of a single water and methanol molecule when
      stored in an ion trap mass spectrometer: complexes with aliphatic amino acids and
      with 4-fluorophenylalanine formed the adduct ions whereas complexes with
      phenylalanine and tryptophan did not. In this study we compared the tendency of
      the Ag(+) complexes derived from phenylalanine, 4-fluorophenylalanine, 4
      hydroxyphenylalanine (tyrosine), 4-bromophenylalanine, 4-nitrophenylalanine and
      aminocyclohexanepropionic acid to form water adducts when stored, without further
      activation, in the ion trap for times ranging from 1 to 500 ms. Because the
      donation of pi electron density to the Ag(+) ion is a likely determining factor
      in complex reactivity, our aim in the present study was to determine
      qualitatively the influence of para-position substituents on the aromatic ring on
      the formation of the water adducts. Our results show that the reactivity of the
      complexes is influenced significantly by the presence of the various
      substituents. Decreases in [M + Ag](+) ion abundance, and increases in adduct ion
      abundance, both measured as a function of storage time, follow the trend -NO(2) >
      -Br > -F > -OH > -H. The complex of Ag(+) with 4-nitrophenylalanine was nearly as
      reactive towards water as the Ag(+) complex with aminocyclohexanepropionic acid,
      the last being an amino acid devoid of pi character in the ring system. Collision
      induced dissociation of the [M + Ag](+) species derived from the amino acids
      produces, among other products, Ag(+) complexes with a para-substituted
      phenylacetaldehyde: complexes that also form adduct species when stored in the
      ion trap. The trends in adduct ion formation exhibited by the aldehyde-Ag(+)
      complex ions were similar to those observed for the precursor complexes of Ag(+)
      and the amino acids, confirming the influence of the ring substituent.

PMID- 11948849
TI  - Effects of liquid chromatography mobile phase buffer contents on the ionization
      and fragmentation of analytes in liquid chromatographic/ionspray tandem mass
      spectrometric determination.
AB  - The effects of liquid chromatography mobile phase buffer contents on the
      ionization and fragmentation of drug molecules in liquid chromatographic/ionspray
      tandem mass spectrometric (LC/MS/MS) determination were evaluated for simvastatin
      (SV) and its hydroxy acid (SVA). The objective was to improve further the
      sensitivity for SV by overcoming the unfavorable condition caused by the
      formation of multiple major adduct ions and multiple major fragment ions when
      using ammonium as LC mobile phase buffer. Mobile phases (70:30 acetonitrile
      buffer, 2 mM, pH 4.5) with buffers made from ammonium, hydrazine or alkyl
      (methyl, ethyl, dimethyl or trimethyl)-substituted ammonium acetate were
      evaluated. Q1 scan and product ion scan spectra were obtained for SV in each of
      the mobile phases under optimized conditions. The results showed that, with the
      alkylammonium buffers, the alkylammonium-adducted SV was observed as the only
      major molecular ion, while the formation of other adduct ions ([M + H](+), [M +
      Na](+) and [M + K](+)) was successfully suppressed. On the other hand, product
      ion spectra with a single major fragment ion were not observed for any of the
      alkylammonium-adducted SVs. The affinity of the alkylammoniums to SV and the
      basicity of the alkylamines are believed to be factors influencing the formation
      and abundance of molecular and fragment ions, respectively. Methylammonium
      acetate provided the most favorable condition among all the buffers evaluated and
      improved the sensitivity several-fold for SV in LC/MS/MS quantitation compared
      with that obtained using ammonium acetate buffer. Better precision for SV in both
      Q1 and SRM scans was observed when using methylammonium buffer compared with
      those using ammonium buffer. The mobile phase buffer contents did not seem to
      affect the ionization, fragmentation and chromatography of SVA. The results of
      this evaluation can be applied to similar situations with other organic molecules
      in ionspray LC/MS/MS determination.

PMID- 11948851
TI  - Current literature in mass spectrometry.

PMID- 11948850
TI  - Nevirapine quantification in human plasma by high-performance liquid
      chromatography coupled to electrospray tandem mass spectrometry. Application to
      bioequivalence study.
AB  - A rapid, sensitive and specific method to quantify nevirapine in human plasma
      using dibenzepine as the internal standard (IS) was developed and validated. The
      method employed a liquid-liquid extraction. The analyte and the IS were
      chromatographed on a C(18) analytical column, (150 x 4.6 mm i.d. 4 microm) and
      analyzed by tandem mass spectrometry in the multiple reaction monitoring mode.
      The method had a chromatographic run time of 5.0 min and a linear calibration
      curve over the range 10-5000 ng ml(-1) (r(2) > 0.9970). The between-run
      precision, based on the relative standard deviation for replicate quality
      controls was 1.3% (30 ng ml(-1)), 2.8% (300 ng ml(-1)) and 3.6% (3000 ng ml(-1)).
      The between-run accuracy was 4.0, 7.0 and 6.2% for the above-mentioned
      concentrations, respectively. This method was employed in a bioequivalence study
      of two nevirapine tablet formulations (Nevirapina from Far-Manguinhos, Brazil, as
      a test formulation, and Viramune from Boehringer Ingelheim do Brasil Quimica e
      Farmaceutica, as a reference formulation) in 25 healthy volunteers of both sexes
      who received a single 200 mg dose of each formulation. The study was conducted
      using an open, randomized, two-period crossover design with a 3 week washout
      interval. The 90% confidence interval (CI) of the individual ratio geometric mean
      for Nevirapina/Viramune was 96.4-104.5% for AUC((0-last)), 91.4-105.1% for AUC((0
      infinity)) and 95.3-111.6% for C(max) (AUC = area under the curve; C(max) = peak
      plasma concentration). Since both 90% CI for AUC((0-last)) and AUC((0-infinity))
      and C(max) were included in the 80-125% interval proposed by the US Food and Drug
      Administration, Nevirapina was considered bioequivalent to Viramune according to
      both the rate and extent of absorption.

PMID- 11948853
TI  - PARP-1: a regulator of genomic stability linked with mammalian longevity.

PMID- 11948854
TI  - Origins of RNA catalysis in the hairpin ribozyme.

PMID- 11948856
TI  - Synthesis of solid-supported mirror-image sugars: a novel method for selecting
      receptors for cellular-surface carbohydrates.
AB  - We introduced a novel method, through mirror-image phage display, for the
      identification of high-affinity D-peptides to target specific cell-surface
      carbohydrates. Both 3-deoxy-alpha-L-manno-2-octulosonic acid (L-KDO) and L-sialic
      acid and an L-sialo-disaccharide have been synthesized and attached to a solid
      support for selection of high-affinity peptide binders displayed on phages. Our
      initial studies in this effort produce single-chain Fab sequences and
      dodecapeptides that bind to sialic acid and KDO with nanomolar and high
      micromolar affinity.

PMID- 11948855
TI  - Artificial nucleases.
AB  - The oxidation of DNA and RNA provides a facile approach for investigating the
      interaction of nucleic acids with proteins and oligonucleotides. In this article,
      we have outlined our understanding of the mechanism of DNA scission by 1,10
      phenanthroline-copper(I) in the presence of hydrogen peroxide. We also discuss
      results obtained by using 1,10-phenanthroline-oligonucleotide conjugates in
      probing the size of the transcriptionally active open complex. Finally, we
      outline an effective method for converting DNA-binding proteins into site
      specific modification agents by using 1,10-phenanthroline-copper(I).

PMID- 11948857
TI  - Novel hyperbranched glycomimetics recognized by the human mannose receptor:
      quinic or shikimic acid derivatives as mannose bioisosteres.
AB  - The mannose receptor mediates the internalization of a wide range of molecules or
      microorganisms in a pattern recognition manner. Therefore, it represents an
      attractive entry for specific drug, gene, or antigen delivery to macrophages and
      dendritic cells. In an attempt to design novel effective synthetic mannose
      receptor ligands, quinic and shikimic acid were selected as putative mannose
      mimics on the basis of X-ray crystallographic data from the related rat mannose
      binding lectin. As the mannose receptor preferentially binds to molecules
      displaying several sugar residues, fluorescein-labeled cluster quinic and
      shikimic acid derivatives with valencies of two to eight were synthesized. Their
      mannose receptor mediated uptake was assayed on monocyte-derived human dendritic
      cells by cytofluorimetric analysis. Mannose-receptor specificity was further
      assessed by competitive inhibition assays with mannan, by confocal microscopy
      analysis, and by expression of the mannose receptor in transfected Cos-1 cells.
      Constructs derived from both quinic and shikimic acid were efficiently recognized
      by the mannose receptor with an optimum affinity for the molecules with a valency
      of four. As a result, commercially available quinic and shikimic acids appear as
      stable mannose bioisosteres, which should prove valuable tools for specific cell
      delivery.

PMID- 11948858
TI  - Highly selective glycosylated prodrugs of cytostatic CC-1065 analogues for
      antibody-directed enzyme tumor therapy.
AB  - Novel prodrugs of the cytotoxic antibiotic CC-1065 for an antibody-directed
      enzyme prodrug therapy (ADEPT) were prepared that show an excellent selectivity
      with a high toxicity of the corresponding drug. In particular, the seco-CBI
      analogue of CC-1065, 1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benz[e]indole, as
      well as the novel methyl-seco-CBI analogue 1-(1'-chloroethyl)-5-hydroxy-1,2
      dihydro-3H-benz[e]indole, were synthesized and transformed into their
      galactosides 10 a and 10 b, respectively. These galactosides can be cleaved with
      beta-D-galactosidase to give the free cytotoxic compounds. They were tested in in
      vitro cytotoxicity assays by using human bronchial carcinoma cells of line A549
      in the presence and in the absence of beta-D-galactosidase. While the seco-CBI
      prodrugs revealed only modest selectivity, prodrugs of the methyl-seco-CBI
      analogue bearing an anti orientation of the substituents at the two stereogenic
      centers of the N-heterocycle displayed an excellent selectivity with an ED(50)
      quotient of about 750. The cytotoxicity of the corresponding phenol was rather
      high, with an ED(50) of 1.3 nM. The diastereomer with a syn orientation at the
      stereogenic centers was much less toxic.

PMID- 11948859
TI  - Improved enantioselectivity of a lipase by rational protein engineering.
AB  - A model based on two different binding modes for alcohol enantiomers in the
      active site of a lipase allowed rational redesign of its enantioselectivity. 1
      Halo-2-octanols were poorly resolved by Candida antarctica lipase B. Interactions
      between the substrates and the lipase were investigated with molecular modeling.
      Unfavorable interactions were found between the halogen moiety of the fast
      reacting S enantiomer and a region situated at the bottom of the active site
      (stereoselectivity pocket). The lipase was virtually mutated in this region and
      energy contour maps of some variants displayed better interactions for the target
      substrates. Four selected variants of the lipase were produced and kinetic
      resolution experiments were undertaken with these mutants. Single point mutations
      gave rise to one variant with doubled enantioselectivity as well as one variant
      with annihilated enantioselectivity towards the target halohydrins. An increased
      volume of the stereoselectivity pocket caused a decrease in enantioselectivity,
      while changes in electrostatic potential increased enantioselectivity. The
      enantioselectivity of these new lipase variants towards other types of alcohols
      was also investigated. The changes in enantioselectivity caused by the mutations
      were well in agreement with the proposed model concerning the chiral recognition
      of alcohol enantiomers by this lipase.

PMID- 11948860
TI  - On the antimicrobial and hemolytic activities of amphiphilic beta-peptides.

PMID- 11948861
TI  - The large fragment of Escherichia coli DNA polymerase I can synthesize DNA
      exclusively from fluorescently labeled nucleotides.

PMID- 11948862
TI  - Dependence of concanavalin A binding on anomeric configuration, linkage type, and
      ligand multiplicity for thiourea-bridged mannopyranosyl-beta-cyclodextrin
      conjugates.

PMID- 11948863
TI  - A mechanism of benzoic acid biosynthesis in plants and bacteria that mirrors
      fatty acid beta-oxidation.

PMID- 11948865
TI  - Scanning force microscopy of artificial membranes.
AB  - Visualization of biological membranes by scanning force microscopy (SFM) has
      tremendously improved the current understanding of protein-lipid interactions
      under physiological conditions. SFM is the only tool to directly image processes
      on surfaces in aqueous solution at molecular resolution. Besides being a
      supportive means to confirm results on lipid phases and domains obtained from
      fluorescence spectroscopy, calorimetry, and X-ray crystallography, SFM has
      contributed distinct aspects on the formation of 2D crystals of various membrane
      confined proteins and morphological changes of membranes due to the interaction
      of peptides and proteins. This review will focus on recent results in SFM imaging
      of artificial solid-supported membranes, their phase behavior as a response to
      the environment, and changes in membrane morphology induced by the partitioning
      of peptides and proteins.

PMID- 11948866
TI  - Chemistry and ecology of toxic birds.

PMID- 11948867
TI  - Partially folded conformations in the folding pathway of bovine carbonic
      anhydrase II: a fluorescence spectroscopic analysis.
AB  - GdmCl-, urea-, and pH-induced unfolding pathways of bovine carbonic anhydrase II
      have been analyzed by using changes induced by different denaturing agents in
      intensity, anisotropy, life time, and parameter A value of intrinsic fluorescence
      as well as intensity and life time of ANS (ammonium salt of 8-anilinonaphthalene
      1-sulfonic acid) fluorescence. The formation of several stable unfolding
      intermediates, some of which were not observed previously, has been established.
      This was further confirmed by representation of fluorescence data in terms of a
      "phase diagram", that is, I(lambda1) versus I(lambda2) dependence, where
      I(lambda1) and I(lambda2) are the fluorescence intensity values measured at
      wavelengths lambda(1) and lambda(2), respectively.

PMID- 11948868
TI  - Wedgelike glycodendrimers as inhibitors of binding of mammalian galectins to
      glycoproteins, lactose maxiclusters, and cell surface glycoconjugates.
AB  - Galectins are mammalian carbohydrate-binding proteins that are involved in cell
      cell and cell-matrix adhesion, cell migration, and growth regulation with
      relevance to inflammation and tumor spread. These important functions account for
      the interest to design suitable low molecular weight inhibitors that match the
      distinct modes of presentation of the carbohydrate recognition domains of the
      different galectin subfamilies. Using 3,5-di-(2-aminoethoxy)benzoic acid as the
      branching unit, wedgelike glycodendrimers with two, four, and eight lactose
      moieties (G1-G3) were synthesized. They were tested in solid-phase competition
      assays with lactose maxiclusters and various N-glycan branching profiles
      (miniclusters) as the matrix and also in cell assays. Prototype galectins-1 and 
      7, chimera-type galectin-3, a plant (AB)(2) toxin, and a lactose-binding
      immunoglobulin G fraction from human serum were the carbohydrate-binding targets.
      Potent inhibition and remarkable cluster effects were seen for the homodimeric
      galectin-1, especially in combination with biantennary N-glycans as the matrix.
      Remarkably, for the tetravalent G2 glycodendrimer, the inhibitory potency of each
      lactose unit reached a maximum value of 1667 relative to free lactose. In
      haemagglutination experiments as a model for cell adhesion, galectin-3 was
      markedly sensitive to increased sugar valency and a relative potency per lactose
      of 150 was reached. The spatial orientation of the carbohydrate recognition
      domains of the endogenous lectins and the branching pattern of the carbohydrates
      of the glycoprotein matrices used are both important factors in the design and
      synthesis of glycodendrimers with galectin-selective properties.

PMID- 11948869
TI  - Cooperativity between electrons and protons in a monomeric cytochrome c(3): the
      importance of mechano-chemical coupling for energy transduction.
AB  - To fully understand the structural bases for the mechanisms of biological energy
      transduction, it is essential to determine the microscopic thermodynamic
      parameters which describe the properties of each centre involved in the
      reactions, as well as its interactions with the others. These interactions
      between centres can then be interpreted in the light of structural features of
      the proteins. Redox titrations of cytochrome c(3) from Desulfovibrio
      desulfuricans ATCC 27774 followed by NMR and visible spectroscopy were analysed
      by using an equilibrium thermodynamic model. The network of homotropic and
      heterotropic cooperativities results in the coupled transfer of electrons and
      protons under physiological conditions. The microscopic characterisation allows
      the identification of several pairs of centres for which there are clear
      conformational (non-Coulombic) contributions to their coupling energies, thus
      establishing the existence of localised redox- and acid-base-linked structural
      modifications in the protein (mechano-chemical coupling). The modulation of
      interactions between centres observed for this cytochrome may be an important
      general phenomenon and is discussed in the framework of its physiological
      function and of the current focus of energy transduction research.

PMID- 11948870
TI  - Exploiting conformationally constrained peptidomimetics and an efficient human
      compatible delivery system in synthetic vaccine design.
AB  - Peptide and protein mimetics are potentially of great value in synthetic vaccine
      design. The mimetics should function by stimulating the immune system to produce
      antibodies that recognize the intact parasite. Also the mimetics should be
      presented to the immune system in a way that leads to efficient antibody
      production. Here we investigate the application of cyclic peptidomimetics
      presented on immunopotentiating reconstituted influenza virosomes (IRIVs), a form
      of antigen delivery that is licensed already for human clinical use, in synthetic
      vaccine design. We focus on the central (NPNA)(n) repeat region of the
      circumsporozoite (CS) protein of the malaria parasite Plasmodium falciparum as a
      model system. Cyclic peptidomimetics of the NPNA repeats were incorporated into
      both an IRIV and (for comparison) a multiple-antigen peptide (MAP). Both IRIV and
      MAP delivery forms induced mimetic-specific humoral immune responses in mice, but
      only with the mimetic-IRIV preparations did a significant fraction of the
      elicited antibodies cross-react with sporozoites. The results demonstrate that
      IRIVs are a delivery system suitable for the efficient induction of antibody
      responses against conformational epitopes by use of cyclic template-bound
      peptidomimetics. Combined with combinatorial chemistry, this approach may have
      great potential for the rapid optimization of molecularly defined synthetic
      vaccine candidates against a wide variety of infectious agents.

PMID- 11948871
TI  - Cryophotolysis of ortho-nitrobenzyl derivatives of enzyme ligands for the
      potential kinetic crystallography of macromolecules.

PMID- 11948872
TI  - The experimentally elusive oxidant of cytochrome P450: a theoretical "trapping"
      defining more closely the "real" species.

PMID- 11948874
TI  - Discovery of superior enzymes by directed molecular evolution.

PMID- 11948875
TI  - Diels-Alderases.

PMID- 11948876
TI  - A fast and efficient metal-mediated oxidation of isoniazid and identification of
      isoniazid-NAD(H) adducts.
AB  - It is currently believed that isoniazid (INH) is oxidised inside Mycobacterium
      tuberculosis to generate, by covalent attachment to the nicotinamide ring of
      NAD(H) (beta-nicotinamide adenine dinucleotide), a strong inhibitor of InhA, an
      enzyme essential for mycolic acid biosynthesis. This work was carried out to
      characterise the InhA inhibitors (named INH-NAD(H) adducts) which are generated,
      in the presence of the nicotinamide coenzyme NAD+, by oxidation of INH with
      manganese(III) pyrophosphate, a nonenzymatic and efficient oxidant used to mimic
      INH activation by the catalase-peroxidase KatG inside M. tuberculosis. The
      oxidation process is almost complete in less than 15 minutes (in comparison to
      the slow activation obtained in the KatG-dependent process (2.5 hours) or in the
      nonenzymatic O2/Mn(II)-dependent activation (5 hours)). The alkylation of NAD+ by
      the postulated isonicotinoyl radical generates, in solution, a family of INH
      NAD(H) adducts. Analyses with liquid chromatography/electrospray ionisation mass
      spectrometry (LC/ESI-MS) and experiments performed with 18O- and 2H-labelled
      substrates allowed us to propose two open and four hemiamidal cyclised
      dihydropyridine structures as the main forms present in solution; these result
      from the combination of the isonicotinoyl radical and the nicotinamide part of
      NAD+. A small amount of a secondary oxidation product was also detected.
      Structural data on the forms present in solution should help in the design of
      inhibitors of enzymes involved in the biosynthesis of mycolic acids to act as
      potential antituberculosis drugs.

PMID- 11948877
TI  - Chemoenzymatic synthesis of biotinylated nucleotide sugars as substrates for
      glycosyltransferases.
AB  - The enzymatic oxidation of uridine 5'-diphospho-alpha-D-galactose (UDP-Gal) and
      uridine 5'-diphospho-N-acetyl-alpha-D-galactosamine (UDP-GalNAc) with galactose
      oxidase was combined with a chemical biotinylation step involving biotin-epsilon
      amidocaproylhydrazide in a one-pot synthesis. The novel nucleotide sugar
      derivatives uridine 5'-diphospho-6-biotin-epsilon-amidocaproylhydrazino-alpha-D
      galactose (UDP-6-biotinyl-Gal) and uridine 5'-diphospho-6-biotin-epsilon
      amidocaproylhydrazino-N-acetyl-alpha-D-galactosamine (UDP-6-biotinyl-GalNAc) were
      synthesized on a 100-mg scale and characterized by mass spectrometry (fast atom
      bombardment and matrix-assisted laser desorption/ionization time of flight) and
      one/two dimensional NMR spectroscopy. It could be demonstrated for the first
      time, by use of UDP-6-biotinyl-Gal as a donor substrate, that the human
      recombinant galactosyltransferases beta3Gal-T5, beta4Gal-T1, and beta4Gal-T4
      mediate biotinylation of the neoglycoconjugate bovine serum albumin-p-aminophenyl
      N-acetyl-beta-D-glucosaminide (BSA-(GlcNAc)17) and ovalbumin. The detection of
      the biotin tag transferred by beta3Gal-T5 onto BSA-(GlcNAc)17 with streptavidin
      enzyme conjugates gave detection limits of 150 pmol of tagged GlcNAc in a Western
      blot analysis and 1 pmol of tagged GlcNAc in a microtiter plate assay. The degree
      of Gal-biotin tag transfer onto agalactosylated hybrid N-glycans present at the
      single glycosylation site of ovalbumin was dependent on the Gal-T used (either
      beta3Gal-T5, beta4Gal-T4, or beta4Gal-T1), which indicates that the acceptor
      specificity may direct the transfer of the Gal-biotin tag. The potential of this
      biotinylated UDP-Gal as a novel donor substrate for human galactosyltransferases
      lies in the targeting of distinct acceptor structures, for example, under
      galactosylated glycoconjugates, which are related to diseases, or in the quality
      control of glycosylation of recombinant and native glycoproteins.

PMID- 11948878
TI  - A membrane-bound cytochrome c3: a type II cytochrome c3 from Desulfovibrio
      vulgaris Hildenborough.
AB  - A new tetraheme cytochrome c3 was isolated from the membranes of Desulfovibrio
      vulgaris Hildenborough (DvH). This cytochrome has a molecular mass of 13.4 kDa
      and a pI of 5.5 and contains four heme c groups with apparent reduction
      potentials of -170 mV, -235 mV, -260 mV and -325 mV at pH 7.6. The complete
      sequence of the new cytochrome, retrieved from the preliminary data of the DvH
      genome, shows that this cytochrome is homologous to the "acidic" cytochrome c3
      from Desulfovibrio africanus (Da). A model for the structure of the DvH
      cytochrome was built based on the structure of the Da cytochrome. Both
      cytochromes share structural features that distinguish them from other cytochrome
      c3 proteins, such as a solvent-exposed heme 1 surrounded by an acidic surface
      area, and a heme 4 which lacks most of the surface lysine patch proposed to be
      the site of hydrogenase interaction in other cytochrome c3 proteins. Furthermore,
      in contrast to previously discovered cytochrome c3 proteins, the genes coding for
      these two cytochromes are adjacent to genes coding for two membrane-associated
      FeS proteins, which indicates that they may be part of membrane-bound
      oxidoreductase complexes. Altogether these observations suggest that the DvH and
      Da cytochromes are a new type of cytochrome c3 proteins (Type II: TpII-c3) with
      different redox partners and physiological function than the other cytochrome c3
      proteins (Type I: TpI-c3). The DvH TpII-c3 is reduced at considerable rates by
      the two membrane-bound [NiFe] and [NiFeSe] hydrogenases, but catalytic amounts of
      TpI-c3 increase these rates two- and fourfold, respectively. With the periplasmic
      [Fe] hydrogenase TpII-c3 is reduced much slower than TpI-c3, and no catalytic
      effect of TpI-c3 is observed.

PMID- 11948879
TI  - Assignment of the nonexchanging protons of the alpha-spectrin SH3 domain by two-
      and three-dimensional 1H-13C solid-state magic-angle spinning NMR and comparison
      of solution and solid-state proton chemical shifts.
AB  - The assignment of nonexchanging protons of a small microcrystalline protein, the
      alpha-spectrin SH3 domain (7.2 kDa, 62 residues), was achieved by means of three
      dimensional (3D) heteronuclear (1H-13C-13C) magic-angle spinning (MAS) NMR
      dipolar correlation spectroscopy. With the favorable combination of a high B(0)
      field, a moderately high spinning frequency, and frequency-switched Lee-Goldburg
      irradiation applied during 1H evolution, a proton linewidth < or =0.5 ppm at 17.6
      Tesla was achieved for the particular protein preparation used. A comparison of
      the solid-state 1H chemical shifts with the shifts found in solution shows a
      remarkable similarity, which reflects the identical protein structures in
      solution and in the solid. Significant differences between the MAS solid- and
      liquid-state 1H chemical shifts are only observed for residues that are located
      at the surface of the protein and that exhibit contacts between different SH3
      molecules. In two cases, aromatic residues of neighboring SH3 molecules induce
      pronounced upfield ring-current shifts for protons in the contact area.

PMID- 11948880
TI  - Design and evaluation of pilicides: potential novel antibacterial agents directed
      against uropathogenic Escherichia coli.

PMID- 11948881
TI  - Catalysis by mutants of methylmalonyl-CoA mutase: a theoretical rationalization
      for a change in the rate-determining step.

PMID- 11948882
TI  - Kinetic monitoring of self-replicating systems through measurement of
      fluorescence resonance energy transfer.

PMID- 11948884
TI  - Randomized comparison of Vasoseal and Angioseal closure devices in patients
      undergoing coronary angiography and angioplasty.
AB  - AngioSeal (AS) and VasoSeal (VS) are collagen-based arterial closure devices
      utilized to achieve earlier hemostasis and ambulation in diagnostic and
      interventional percutaneous procedures. To our knowledge, there has been no
      randomized studies comparing these two devices as approved for use in the United
      States. One hundred fifty-seven patients were randomized to receive either the 8
      Fr AS (n = 79) or VS (n = 78) closure device. Data on 95 patients who had
      coronary angiography (49 AS, 46 VS) and 55 patients who underwent angioplasty (28
      AS, 27 VS) were completed. Heparin was not administered during the coronary
      angiogram procedure. The activated clotting time was kept at approximately 300
      sec during angioplasty. Patients on coumadin or GP IIb/IIIa platelet inhibitors
      were not included in this study. The time unit interval to achieve hemostasis in
      this study was based on the time the AS tension spring was left over the common
      femoral artery following collagen deployment as per the manufacturer's
      instructions (20 min). Time to hemostasis, time to ambulation, and major and
      minor complications were prospectively recorded. Two-tailed t-test and chi-square
      analysis were performed on continuous and dichotomous variables, respectively.
      For the angiogram-only subgroup, time (min) to hemostasis (20.51 +/- 4.36 vs.
      18.59 +/- 11.77; P = 0.30) and ambulation (145.71 +/- 124 vs. 109.89 +/- 60.37; P
      = 0.075) were not statistically different for the AS and VS, respectively.
      Similarly, for the angioplasty subgroup, time (min) to hemostasis (24.23 +/-
      12.70 vs. 19.57 +/- 2.27; P = 0.077) and ambulation (607.32 +/- 344.22 vs. 486.48
      +/- 200.37; P = 0.12) were not statistically different for both AS and VS,
      respectively. Furthermore, there were no statistical differences in deployment
      failure, major, minor, or total complication rates between the two devices. In
      the absence of GP IIb/IIIa inhibitors, VS and the 8 Fr AS devices have
      statistically similar time to hemostasis and ambulation as well as device
      failures and complication rates following coronary angiography and angioplasty.

PMID- 11948885
TI  - Plug vs. plug.

PMID- 11948886
TI  - Stenting of bifurcation lesions using the Bestent: a prospective dual-center
      study.
AB  - Treatment of bifurcation lesions remains a technical challenge. Among 13 stents
      previously tested in a bench study, the Bestent seemed of particular interest in
      this indication as it provided good access to the side branch after stent
      implantation in the main branch associated with a satisfactory coverage of the
      lesion after kissing balloon inflation. The use of Bestent implanted in the main
      branch or both branches for treatment of bifurcation lesions involving a side
      branch > or = 2.2 mm in diameter was prospectively evaluated in a dual-center
      prospective study with a prospective 6-month clinical follow-up. All angiographic
      documents were analyzed by an independent corelab (CORISIS). Between 11 September
      1997 and 21 February 1998, 96 patients were consecutively included (mean age,
      63.7 +/- 11.4 years; 81.3% male; 58.3% with unstable angina and 6.3% acute
      myocardial infarction). The lesion involved the left anterior descending-diagonal
      coronary bifurcation in 55% of cases, left circumflex-marginal 23%, posterior
      descending-postero-lateral 12%, distal left main 6%, and others 4%. The main
      branch (proximal reference diameter: 3.43 +/- 0.45 mm) was stented in 98% of
      cases and the side branch (2.72 +/- 0.38 mm) in 38% (both branches in 34% of
      cases). T-stenting or provisional T-stenting was used in 88% of cases and final
      kissing balloon inflation was performed in 78% of cases. Procedural success was
      obtained in 100% of cases in the main branch and 98% in both branches. Major
      cardiac and cerebral events (MACCE) during hospitalization occurred in 4.2% of
      cases, non-Q-wave myocardial infarction (MI) in 3.1%, Q-wave MI in 1.0%, repeat
      PTCA in 2.1%; there were no major access site complication, no emergency coronary
      artery bypass grafting operation, no death. At 6-month follow-up, total MACCE
      rate was 14.6% (Q-wave MI, 3.1%; non-Q-wave MI, 3.1%; target vessel
      revascularization, 9.4%; death, 2.1%). Patients with target vessel
      revascularization (TVR) had restenosis of both branches in 22.2% of cases, main
      branch in 22.2%, and side branch in 55.6%. This study shows that using a simple
      strategy of provisional T-stenting of the side branch in the majority of cases,
      the Bestent can be used for treating bifurcation lesions with a high rate of
      success and an acceptable rate of TVR at 6-month follow-up.

PMID- 11948887
TI  - The bifurcation lesion: more evidence that a new lesion classification system
      should be widely adopted.

PMID- 11948889
TI  - Comparison of two different methods of quantitative coronary angiography in
      patients with acute coronary syndromes.
AB  - The minimal cost algorithm (MCA) commonly used for quantitative coronary
      arteriography has limitations in definition of complex lesion morphology. A
      gradient field transform (GFT) algorithm has been designed for the better
      analysis of complex lesions. We compared MCA with GFT in angiograms of 125
      patients in the Myocardial Infarction with Novastan and t-PA (MINT) trial. Lesion
      border definition was rated as one (poor), two (good), or three (very good).
      While MCA- and GFT-derived reference diameters (RDs) were similar, GFT yielded
      smaller minimal lumen diameter (MLD) than MCA by 0.22 +/- 0.31 mm (P < 0.01), and
      the difference between GFT- and MCA-derived MLDs increased with decreasing MLD.
      Mean percent diameter stenosis (% DS) was 9.1% +/- 11.1% greater by GFT (P <
      0.001). Lesion border definition in simple lesions was similar (not significantly
      different). However, in complex lesions GFT performed better (2.49 +/- 0.61 vs.
      2.11 +/- 0.74; P < 0.05). Thus, GFT appears to improve analysis of complex
      lesions compared to MCA. GFTs role in angiographic trials and clinical practice
      deserves further study.

PMID- 11948888
TI  - Clopidogrel therapy in patients undergoing coronary stenting: value of a high
      loading-dose regimen.
AB  - The objective of this study was to assess the value of a clopidogrel regimen
      based on a high loading dose initiated before the stent placement procedure. A
      consecutive series of 864 patients treated with a high-loading-dose clopidogrel
      regimen (600 mg given 2-4 hr prior to intervention) was compared with 870
      patients treated with conventional ticlopidine therapy. Abciximab was given
      periprocedurally in 62% of the patients. The composite endpoint of death,
      myocardial infarction, or urgent revascularization was reached by 39 (4.5%)
      clopidogrel patients and 59 (6.8%) ticlopidine patients. Clopidogrel therapy was
      associated with a 35% reduction of the risk for early adverse events (odds ratio
      0.65; 95% confidence interval, 0.43-0.98). Thus, a high-loading-dose clopidogrel
      regimen in patients undergoing coronary artery stenting was safe and led to a
      more favorable clinical outcome than conventional therapy with ticlopidine
      regardless of concomitant treatment with abciximab.

PMID- 11948890
TI  - Percutaneous transvenous mitral commissurotomy: immediate and long-term follow-up
      results.
AB  - Percutaneous transvenous mitral commissurotomy has emerged as an effective
      nonsurgical technique for the treatment of patients with symptomatic mitral
      stenosis. This report highlights the immediate and long-term follow-up results of
      this procedure in an unselected cohort of patients with rheumatic mitral stenosis
      from a single center. It was performed in a total of 4,850 patients using double
      balloon in 320 (6.6%), flow-guided Inoue balloon technique in 4,374 (90.2%), and
      metallic valvulotome in 156 (3.2%) patients. Their age range was 6.5-72 years
      (mean, 27.2 +/- 11.2 years) and 1,552 (32%) patients were under 20 years of age.
      Atrial fibrillation was present in 702 (14.5%) patients. No patient was rejected
      on the basis of echocardiographic score using the Wilkins criteria.
      Echocardiographic score of > or = 8 was present in 1,632 (33.6%) patients, of
      which 103 (2.1%) had densely calcified (Wilkins score 4+) valve. A detailed
      clinical and echocardiographic (two-dimensional, continuous-wave Doppler and
      color-flow imaging) assessment was done at every 3 months for the first year and
      at 6-month interval thereafter. The procedure was technically successful in 4,838
      (99.8%) patients but optimal result was achieved in 4,408 (90.9%) patients with
      an increase in mitral valve area (MVA) from 0.7 +/- 0.2 to 1.9 +/- 0.3 cm(2) (P <
      0.001) and a reduction in mean transmitral gradient from 29.5 +/- 7.0 to 5.9 +/-
      2.1 mm Hg (P < 0.001). The mean left atrial pressure decreased from 32.1 +/- 9.8
      to 13.1 +/- 6.2 mm Hg (P < 0.001). Although there was no statistically
      significant difference in the MVA achieved between de novo and restenosed valves
      (1.9 +/- 0.3 and 1.8 +/- 0.2 cm(2), respectively; P > 0.05), or between
      noncalcific and calcific valves (2.0 +/- 0.3 and 1.8 +/- 0.2 cm(2), respectively;
      P > 0.05), on the whole MVA obtained after percutaneous transvenous mitral
      commissurotomy was less in restenosed and calcific valves. Ten (0.20%) patients
      had cardiac tamponade during the procedure. Mitral regurgitation appeared or
      worsened in 2,038 (42%) patients, of which 68 (1.4%) developed severe mitral
      regurgitation. Urgent mitral valve replacement was carried out in 52 (1.1%) of
      these patients. Data of 3,500 patients followed over a period of 94 +/- 41 months
      (range, 12-166 months) revealed MVA of 1.7 +/- 0.3 cm(2). Elective mitral valve
      replacement was done in 34 (0.97%) patients. Mitral restenosis was seen in 168
      (4.8%) patients, of which 133 (3.8%) were having recurrence of class III or more
      symptoms. Thus, percutaneous transvenous mitral commissurotomy is an effective
      and safe procedure with gratifying results in high percentage of patients. The
      benefits are sustained in a majority of these patients on long-term follow-up. It
      should be considered as the treatment of choice in patients with rheumatic mitral
      stenosis of all age groups.

PMID- 11948891
TI  - Combined glycoprotein IIb/IIIa receptor inhibition and low-dose fibrinolysis for
      peripheral arterial thrombosis.
AB  - This feasibility study evaluated the therapeutic potential of combined GP
      IIb/IIIa receptor inhibition with abciximab and low-dose fibrinolysis with
      reteplase for treatment of acute femoropopliteal thrombosis. The simultaneous
      intra-arterial administration of abciximab in conjunction with low-dose reteplase
      (< or = 0.5 U/hr) was safe in 13 patients; 2 patients experienced major
      hemorrhagic complication at a reteplase dose of 1 U/hr. The primary success rate
      was 100%; all patients experienced an excellent clinical response with no
      clinical evidence of distal embolization. No patient required repeat endovascular
      or surgical revascularization during mean follow-up of 9.3 months. This promising
      new thrombolytic strategy for the treatment of peripheral arterial occlusive
      disease requires further study.

PMID- 11948892
TI  - Sequential vs. kissing balloon angioplasty for stenting of bifurcation coronary
      lesions.
AB  - Coronary angioplasty of bifurcation lesions remains a technical challenge and is
      believed to result in low procedural success associated with the risk of side
      branch occlusion. Furthermore, long-term results are associated with a high rate
      of reintervention. The aim of the study was to evaluate the immediate and long
      term clinical and angiographic results of sequential vs. simultaneous balloon
      angioplasty (kissing balloon technique) for stenting of bifurcation coronary
      lesions. Between December 1999 and January 2001, 59 patients underwent coronary
      angioplasty because of symptomatic bifurcation lesions type III (i.e., side
      branch originates from within the target lesion of the main vessel, and both main
      and side branch are angiographically narrowed more than 50%). Twenty-six patients
      were treated with simultaneous and 33 patients with sequential balloon
      angioplasty. Main-vessel stent placement was mandatory; side-branch stenting and
      platelet IIb/IIIa antagonists were allowed at the discretion of the operator.
      Kissing balloon technique offered no advantage in terms of procedural success or
      need for repeat target vessel revascularization due to restenosis at 6-month
      follow-up. Using sequential balloon angioplasty, permanent or transient side
      branch compromise rate (TIMI flow < 3) was significantly higher than after
      kissing balloon technique (33% vs. 0%, respectively; P = 0.003). Major clinical
      events in-hospital or at 6-month follow-up, however, showed no significant
      differences. Kissing balloon angioplasty reduces the rate of transient side
      branch occlusion compared to sequential PTCA but does not improve immediate or
      long-term outcome compared to sequential PTCA for stenting of bifurcation
      lesions.

PMID- 11948893
TI  - Safety of coronary stenting early after thrombolysis in patients with acute
      myocardial infarction: one- and six-month clinical and angiographic evolution.
AB  - To determine the feasibility and safety of early posthrombolysis coronary
      stenting and the incidence of further reocclusion, we followed 99 consecutive
      patients with acute myocardial infarction thrombolyzed with rt-PA 2.0 +/- 0.8 hr
      after onset. Culprit artery was stented 14.0 +/- 7.0 hr after thrombolysis. All
      patients underwent clinical and angiographic follow-up at 1 and 6 months.
      Angiographic success was achieved in 99% of cases. Neither major cardiac events
      nor bleeding or vascular complications occurred during hospital stay. At 30 days,
      no events occurred and normal flow persisted in all stented arteries. At 6
      months, only one artery reoccluded (1%), resulting in a nonfatal reinfarction.
      Restenosis rate was 21%. Contribution of the infarcted area to left ventricular
      function significantly increased from baseline to 30-day and to 6-month
      evaluations. Thus, early posthrombolysis stenting is a safe strategy with a low
      reocclusion rate, which seems to allow functional recovery of the infarcted area.
      Further studies are necessary to define its impact on survival and cost
      effectiveness.

PMID- 11948895
TI  - Successful primary angioplasty in Hughes syndrome.
AB  - Acute myocardial infarction is a well-recognized complication of the Hughes
      syndrome but its optimal treatment is uncertain. We report a case of a 42-year
      old man with a history of previous arterial and venous thrombosis who presented
      with an acute myocardial infarction that was successfully treated by primary
      angioplasty and stenting.

PMID- 11948894
TI  - Influence of coronary collateral flow on restenosis following primary angioplasty
      for acute myocardial infarction.
AB  - We investigated the influence of collateral flow on restenosis in 156 consecutive
      acute myocardial infarction (AMI) patients treated with primary angioplasty
      within 12 hr of symptom onset. Collateral flow was quantitatively assessed using
      the pressure-derived fractional collateral flow (PDCF) index. Follow-up
      angiography was performed at 6 months. The patients were classified into two
      groups according to the PDCF index: group I (PDCF index > 24%; n = 55) with good
      collaterals and group II (PDCF index < or = 24%; n = 101) with poor collaterals.
      Baseline characteristics were similar between the two groups, with the exception
      of peak levels of creatine kinase, angiographic collaterals, and TIMI flow 3
      after intervention. The binary restenosis rate was 31.8% in group I and 32.9% in
      group II (P = NS). Use of the stents was the only independent predictor of binary
      restenosis. In conclusions, well-developed collaterals measured by PDCF may not
      predict restenosis following primary angioplasty for AMI.

PMID- 11948896
TI  - Novel technique for stent delivery in tortuous coronary arteries: report of three
      cases.
AB  - We present a novel technique for stent delivery across tortuous lesions. Gentle
      forward pressure was applied on the stent balloon while the balloon was inflated
      to 2-3 atm. This resulted in the balloon and stent crossing the impeding segment
      and settling in the target site where it was deployed with excellent angiographic
      outcome.

PMID- 11948897
TI  - Acute coronary embolism: angiographic diagnosis and treatment with primary
      angioplasty.
AB  - Acute coronary embolism is rarely diagnosed and it may explain why normal
      coronary arteries are found after or even before an acute coronary event in
      patients with thromboembolic risk factors. Emergency coronary angiography was
      performed in three patients with prior normal coronary arteries and an acute
      myocardial infarction, followed by primary angioplasty with low-pressure balloon
      inflations plus stenting and combined antiaggregation with aspirin, clopidogrel,
      and abciximab to disrupt the thrombi and protect distal circulation from
      microemboli. Angiographic success was achieved in 100%, and 6-month follow-up has
      been uneventful on oral anticoagulation and antiaggregation.

PMID- 11948898
TI  - Evaluating the etiology of mechanical valve obstruction: use of clinical
      parameters, fluoroscopy, and echocardiography.
AB  - Prosthetic valve obstruction is a life-threatening complication most commonly
      caused by thrombus, pannus, or both. We report a St. Jude tricuspid valve
      obstruction, initially treated with thrombolytic therapy, found to be caused by
      pannus on pathologic examination. Clinical evaluation and diagnostic evaluation
      with fluoroscopy and echocardiography in distinguishing pannus from thrombus are
      reviewed.

PMID- 11948899
TI  - Transient occlusion of an Angioguard protection system by massive embolization
      during angioplasty of a degenerated aortocoronary saphenous vein graft.
AB  - Distal embolization is the most important complication of balloon dilatation of
      degenerated saphenous vein grafts. We describe a case of massive embolization
      associated with transient occlusion in which larger distal embolization and
      myocardial infarction were avoided despite transient but complete occlusion of a
      filter protection system (Angioguard).

PMID- 11948900
TI  - Endovascular stent implantation in the pulmonary arteries of infants and children
      without the use of a long vascular sheath.
AB  - Endovascular stent implantation for pulmonary artery stenosis requires the use of
      a long, large-bore vascular sheath to insure precise implantation without
      embolization or malposition. A long vascular sheath may be difficult to position
      and usage may be associated with vascular compromise and/or hemodynamic
      embarrassment, especially in infants and small children. We report a new
      technique for pulmonary artery endovascular stent implantation without the use of
      a long sheath. From December 2000 to May 2001, 10 patients underwent implantation
      of 13 Palmaz Corinthian premounted biliary transhepatic stents for pulmonary
      artery stenosis. Median age was 0.8 years (range, 0.5-18.5) and median weight was
      11.8 kg (range, 4.6-65). Patient diagnoses were tetralogy of Fallot (five),
      double outlet right ventricle (three), branch peripheral pulmonary artery
      stenosis (two), single ventricle s/p cavopulmonary shunt (one), and truncus
      arteriosus (one). All Palmaz Corinthian stents were delivered uncovered on Cordis
      Opta LP balloon catheters via short sheaths (6-7 Fr); super-stiff guidewires were
      not always necessary. These stents, with a maximal expanded diameter of 12 mm,
      were placed for peripheral pulmonary artery stenosis as a definitive procedure or
      at the pulmonary artery bifurcation in patients who were expected to undergo
      future open heart surgery. The stents were initially implanted on 4, 6, or 8 mm
      balloon catheters and further expanded if needed. Stents were placed in the right
      pulmonary artery alone in three patients, left pulmonary artery alone in four
      patients, and side-by-side stents were implanted simultaneously in three
      patients. All thirteen stents were implanted successfully in the desired location
      without stent malposition or embolization. Mean angiographic diameter increased
      from 2.5 +/- 1.5 to 5.7 +/- 1.4 mm (P < 0.01) and peak systolic ejection
      gradients decreased from 44 +/- 22 to 14 +/- 11.6 mm Hg (P < 0.01). The uncovered
      delivery of the premounted Palmaz Corinthian stent allowed for precise and safe
      endovascular stent implantation without the hemodynamic and technical problems
      associated with long vascular sheath usage. This technique is useful for the
      palliation of proximal pulmonary artery stenosis and is effective definitive
      treatment for peripheral pulmonary artery stenosis in small infants and children.

PMID- 11948901
TI  - Stent implantation for long-segment coarctation of aorta in infant with facial
      and mediastinal hemangioma.
AB  - We report a case of an infant with an extensive hemangioma encompassing the
      thoracic aorta, associated with complex coarctation. Surgical approach was
      abandoned for fear of bleeding. The complexity of the coarctation made it
      unsuitable for balloon dilation. We implanted a stent with significant
      angiographic improvement and resolution of systemic hypertension.

PMID- 11948903
TI  - Catheter closure of ductus arteriosus in adolescents and adults: what to use?

PMID- 11948902
TI  - Transcatheter closure of patent ductus arteriosus using Gianturco coils in
      adolescents and adults.
AB  - We present the short- and intermediate-term results of transcatheter closure of
      patent ductus arteriosus with Gianturco coils in adolescents and adults. During a
      5-year period, 55 patients (44 females, 11 males) with ages ranging from 14 to 72
      years (median, 23) underwent attempted transcatheter closure of patent ductus
      with the Gianturco coils. The diameter of the narrowest segment of the ductus
      ranged from 0.8 to 7.6 mm (3.9 +/- 1.3 mm). The 55 patients were divided into
      three groups. Group I consisted of nine patients with a ductal diameter < or = 3
      mm, group II consisted of 27 patients with a ductal diameter > 3 mm but < or = 4
      mm, and group III consisted of 19 patients with a ductal diameter > 4 mm. Four-
      to five-loop Gianturco coils were used, which were deployed via retrograde aortic
      route. Multiple-coil technique was generally applied in group II patients.
      Balloon occlusion technique in combination with multiple-coil technique was
      generally used in group III patients. Deployment of coil was successful in 51
      patients (93%) but failed in 4. The success rate of coil deployment in group I,
      II, and III were 100% (9/9), 96% (26/27), and 84% (16/19), respectively. A mean
      of 1.9 +/- 0.7 coils was deployed per patient. Of the four patients with
      unsuccessful coil deployment, three underwent surgery and one received
      implantation with Amplatzer duct occluder. Distal embolization of 21 coils
      occurred in 10 patients (3 in group II and 7 in group III), from whom 20 coils
      were retrieved with a gooseneck snare and 1 coil was removed during surgery. The
      mean diameter of ductus in the 10 patients with distal embolization was
      significantly larger than that in those without (5.2 +/- 1.4 vs. 3.7 +/- 1.1 mm;
      P < 0.01). Among the 51 patients with successful coil deployment, immediate
      complete closure was achieved in 20 (39%), while trivial to mild leak was present
      in 31 (61%). No significant complications were encountered. After a follow-up
      period ranging from 5 to 42 months, four patients had a small residual shunt and
      three underwent a second intervention with complete occlusion. None had left
      pulmonary artery stenosis documented with Doppler echocardiography. Transcatheter
      closure of ductus with the Gianturco coils is safe and feasible in the majority
      of adolescents and adults. Taking high embolization rate in patients with a
      ductus diameter > 4 mm into consideration, controlled-release coils, Buttoned
      device, or Amplatzer duct occluder can be a better choice.

PMID- 11948904
TI  - Persistent redundant Eustachian valve interfering with Amplatzer PFO occluder
      placement: anatomico-clinical and technical implications.
AB  - A 28-year-old man with patent foramen ovale and a prominent Eustachian valve with
      a history of transient ischemic attack underwent transcatheter closure using
      Amplatzer patent foramen ovale occluder. During deployment, some of the prominent
      valve tissue was entrapped on the delivery cable and a piece of the valve was
      extracted unintentionally. Anatomico-clinical and technical implications are
      discussed.

PMID- 11948905
TI  - Recommendations for future trials in the field of access site closure: focusing
      on clinically significant endpoints.

PMID- 11948907
TI  - Amplatzing a 6 Fr Judkins right guiding catheter for increased success in complex
      right coronary artery anatomy.

PMID- 11948909
TI  - Registry for atrial septal defect/patent foramen ovale closure devices for
      platypnea-orthodeoxia syndrome.

PMID- 11948911
TI  - Too good but not good enough: training caught in transition.

PMID- 11948912
TI  - Cooperative E-box regulation of human GLI1 by TWIST and USF.
AB  - Sonic hedgehog signaling plays a critical role in vertebrate patterning, and
      signaling defects are associated with severe birth defects and cancer in man.
      GLI1 encodes a critical transcription activator in this pathway. GLI1 is
      expressed in human basal cell carcinomas and sarcomas. Despite the significance
      of the GLI1 gene in human disease, few immediate upstream regulators of GLI1
      expression are known. We previously demonstrated that a 5' region, including 5'
      flanking sequence, an untranslated exon, and 425 bp of the first intron,
      regulates the human GLI1 gene. Here we show that inactivating mutations in E-box,
      GC box, AP-2, GATA, GSG, PuF, and Zeste sites identified three critical
      regulatory elements, including a GC box that binds Sp1 and two intronic E-boxes
      that bind USF proteins or Twist. Expression of Twist but not a frame shift
      mutation of Twist activates the wild-type human GLI1 regulatory sequences but not
      with inactivating mutations of the E-boxes. Twist activates GLI1 reporter
      expression through E-box +482 but requires binding of USF proteins to E-box +157.
      Twist mutations cause human birth defects and Twist is overexpressed in many
      rhabdomyosarcomas, suggesting that one of Twist's primary roles is the regulation
      of GLI1.

PMID- 11948913
TI  - Wnt-6 is expressed in the ureter bud and induces kidney tubule development in
      vitro.
AB  - The embryonic kidney is a classic developmental model system for studying
      inductive tissue interactions that govern organogenesis. We report here that Wnt
      6 is expressed in the ureter bud, and that cell lines expressing Wnt-6 induce
      nephrogenesis in vitro. Wnt-6 cells induce tubules with similar kinetics to
      spinal cord (SPC) and lead to induced expression of Pax2, Pax8, Sfrp2, and E
      cadherin genes, early markers of tubulogenesis. Moreover, Wnt-6 signaling rescues
      tubulogenesis in mesenchyme separated from Wnt-4 mutant embryos and leads to
      activation of Wnt-4 transcription. Wnt-6 also induces a secondary axis in early
      Xenopus embryos. We conclude that Wnt-6 is a candidate for the ureter epithelium
      derived signal that leads to activation of kidney tubulogenesis via Wnt-4.

PMID- 11948914
TI  - Efficient delivery of dsRNA into zona-enclosed mouse oocytes and preimplantation
      embryos by electroporation.
AB  - Conditions for the electroporation of mouse oocytes and preimplantation embryos
      have been optimised by following the incorporation of rhodamine labeled dextran.
      This procedure includes a step to weaken but not remove the zona pellucida that
      helps achieve good survival. This approach has been applied to introduce double
      stranded RNA for c-mos into oocytes and green fluorescent protein (GFP) into
      transgenic GFP-expressing embryos at the 1- and 4-cell stages. In both cases we
      were able to observe sequence-specific interference with the expression of the
      target gene--a failure of oocytes to arrest at metaphase II and a loss in the
      green fluorescence of embryos by the morula or blastocyst stages. These effects
      could be observed in multiple oocytes or embryos allowed to develop together
      following electroporation.

PMID- 11948915
TI  - Cell-specific transgene expression from a widely transcribed promoter using
      Cre/lox in mice.
AB  - Mice carrying two or more transgenes are used frequently to evaluate oncogene
      interactions during carcinogenesis. However, neoplastic transformation typically
      results in reduced expression both of differentiation-specific genes and of
      transgenes that use their promoters. In contrast, the more widely expressed
      metallothionein (MT) gene remains expressed at a high level in certain neoplasms,
      including those developing in pancreas. We have developed a system to maintain
      high-level, tissue-specific transgene expression during pancreatic carcinogenesis
      that uses Cre recombinase and a lox site-containing target transgene. Cre was
      expressed in pancreatic acinar cells under control of the elastase promoter (EL).
      Cre-mediated target transgene recombination placed a previously silent open
      reading frame, encoding rat transforming growth factor alpha (TGFalpha), under
      control of the MT gene promoter. As long as DNA rearrangement does not occur in
      other cell types that express MT, TGFalpha expression will be restricted to
      acinar cells. Development of an effective target transgenic mouse required
      evaluation of multiple lineages to identify one with sufficient TGFalpha
      expression to induce pancreatic lesions after transgene rearrangement.

PMID- 11948916
TI  - A novel reporter strain to follow Cre-mediated recombination in T and NK cells.
AB  - The Cre-loxP system permits the generation of mouse models in which the fate of a
      cell can be followed through time. Such approach is of great value in immunology
      because it may allow lineage studies and the dissection of the contribution of
      specific effector T cells to long-term memory responses or autoimmune responses.
      An essential component of such a strategy is the development of appropriate
      reporter strains of mice in which the inducible reporter molecule is not
      immunogenic and is well expressed at the cell surface of T cells. We describe
      here a novel reporter strain of mice that is designed to fulfill these criteria
      and show that this strain permits the monitoring of Cre-mediated recombination in
      both T cells and NK cells.

PMID- 11948917
TI  - Identification of immunological reagents for use in the study of freshwater
      planarians by means of whole-mount immunofluorescence and confocal microscopy.
AB  - In recent years, interest in planarians as a model system for the study of
      metazoan regeneration, adult stem cell biology, and the evolution of metazoan
      body plans has been growing steadily. The availability of RNA interference
      (RNAi), BrdU-labeling of planarian stem cells, and thousands of planarian cDNA
      sequences soon to be released into public databases has opened planarians to
      molecular dissection. However, the successful application of large-scale RNAi
      based screens, for example, will depend in part on the availability of markers to
      characterize the resulting phenotypes. Given the paucity of antibodies available
      for the study of planarian biology, we have screened various public and
      commercial antibody resources to identify immunoreagents capable of cross
      reacting with planarian tissues. Here we report the identification and
      characterization of 33 such antibodies recognizing a wide variety of tissues in
      freshwater planarians.

PMID- 11948949
TI  - Sir Victor Alexander Haden Horsley (1857-1916): neurosurgeon and neuroscientist.

PMID- 11948951
TI  - Anatomic relation between the nuchal ligament (ligamentum nuchae) and the spinal
      dura mater in the craniocervical region.
AB  - There are inconsistencies between the descriptions of the physical connections
      between the spinal cervical dura and the surrounding tissues. This study was
      undertaken to clarify the relationship between the spinal dura, the nuchal
      ligament and the suboccipital muscles. Dissections were performed on embalmed
      cadavers: in nine the relevant structures were removed en bloc, whereas in one a
      sagittal section was prepared. In all specimens it was possible to demonstrate
      continuity in the midline between the nuchal ligament and the posterior spinal
      dura at the atlanto-occipital and atlanto-axial intervals. No such attachments
      were found caudal to the arch of the axis. In addition, there was a connective
      tissue bridge between the deep aspect of the rectus capitis posterior minor
      muscle to the transverse fibers of the posterior atlanto-occipital membrane that
      extended laterally to blend with the perivascular tissue of the vertebral
      arteries. The present study is, we believe, the first to describe continuity
      between the nuchal ligament and the dura at the atlanto-occipital interspace, and
      confirms previous descriptions of similar connections at the atlanto-axial level.
      Knowledge of the exact attachments of the dura may contribute to understanding
      the biomechanics of the cervical spine and of the possible etiology of some types
      of cervicogenic headaches.

PMID- 11948950
TI  - Applying circular posterior-hinged craniotomy to malignant cerebral edemas.
AB  - Malignant brain edemas are often fatal, regardless of whether they are treated
      conservatively with sedation, blood pressure management, mannitol-therapy,
      hyperventilation and hypothermia, or non-conservatively with routine trepanation.
      Unfortunately, temporal trepanation may result in significant brain damage
      through herniation of the cerebrum at the edges of the trepanation openings. In
      one case of a 26-year-old male with severe head injury, a circular posterior
      hinged craniotomy (CPHC) was performed after an ineffective unitemporal
      trepanation for evacuation of an acute subdural hematoma. This ultimately
      successful operation prompted experimental and morphologic investigations on a
      new surgical procedure for lowering intracranial pressure (ICP). In 12 of 15
      human cadavers, an experimentally ICP was lowered by a CPHC with between 9-21 mm
      of frontal elevation of the calvaria. Using computer simulation, the frontal
      elevations of the calvaria were "virtually" performed on 3D reconstructions from
      CT scans of skulls, and the intracranial volume gained was measured with a
      computer software program. The volume increase of the cranial cavity showed a
      relatively constant relation to the cranial capacity and was increased by 6.0%
      (+/-0.4%) or 78 cm(3) with a 10 mm elevation and by 12.4% (+/-0.7%) or 160 cm(3)
      with a 20 mm elevation. There were no significant differences with skulls of
      different ages or ethnic origin; however, a significant effect of gender (F =
      7.074; P < or = 0.013) on the gained volume in percent of the cranial capacity
      for the 20 mm elevation was observed. This difference can be explained by the
      inverse relationship between volume increase and cranial capacity (r = -0.507; P
      < or = 0.004).

PMID- 11948952
TI  - Adipose body of the orbit.
AB  - The adipose body of the orbit (ABO) fills most of the orbital cavity, surrounding
      the eyeball, muscles, nerves, and vessels. It was studied in histologic section
      in the three basic planes in the fetus, neonate, and adult. In the retrobulbar
      area, that is, posterior to the eyeball, adipose tissue occupies the space around
      the optic nerve and penetrates between the recti muscles, describing a four
      leafed clover pattern in frontal section. The fatty tissue of the retrobulbar
      area also includes the peripheral ring of fat that lies between the muscles and
      the walls of the orbit. In the part of the peribulbar area located between the
      muscular insertions on the eyeball anteriorly and the emergence of the optic
      nerve from the sclera posteriorly, the pattern of adipose tissue is identical to
      the peripheral ring of fat and the fat between the muscles in the retrobulbar
      area. External to the muscular insertions and the anterior part of the eyeball,
      there is a thin ring of histologically similar fatty tissue that is continuous
      anteriorly with the fatty bodies of the upper and lower eyelids. Histologic
      examination shows that the lobules are large in that part of the retrobulbar area
      within the muscle cone and that they are smaller with more fibrous septa in the
      remaining restricted regions, such as the area between the eyeball and muscles
      and in the rings around the muscles and around the eyeball. In no case was a
      septum found separating the peripheral adipose ring from the fat located within
      the muscle cone.

PMID- 11948953
TI  - Absence of the falx cerebelli in a Chiari II malformation.
AB  - After a review of the literature, we found no descriptions of the falx cerebelli
      in the Chiari II population. Other dural partitions in this group have been well
      described. The aim of our study was to radiologically and at autopsy search for
      the falx cerebelli in this population. We retrospectively analyzed 50 CTs and 50
      MRIs in children with a known Chiari II malformation, searching for either the
      falx cerebelli or internal occipital crest, the bony attachment for the falx
      cerebelli; these structures were also investigated in two patients at autopsy. We
      were unable to observe the falx cerebelli or internal occipital crest on any of
      the radiologic images or at autopsy. We theorize that a "crowded" posterior
      cranial fossa in these patients inhibits the development of the falx cerebelli
      and internal occipital crest.

PMID- 11948954
TI  - Coil-like structure of the inner core of chordae tendineae.
AB  - Scanning electron microscopy was used to examine the chordae tendineae in young
      (approximately 20 years old) and old (approximately 85 years old) cadavers. A
      network of collagen fibrils was observed in both the outer and intersurface
      layers of the chordae tendineae. In young subjects, a regularly arranged series
      of disconnected collagenous ring-like structures surrounded the longitudinal
      collagen bundles forming the inner core of the chordae tendineae. In old
      subjects, the ring-like structures of the chordae tendineae were few or absent.
      The ring-like structures may be related to reducing mechanical stress during the
      tightening, twisting, and slackening of the chordae tendineae.

PMID- 11948955
TI  - Effect of paratenon and repetitive motion on the gliding resistance of tendon of
      extrasynovial origin.
AB  - We measured the gliding resistance of canine and human tendons of intrasynovial
      origin and tendons of extrasynovial origin with and without paratenon, and
      investigated the structure of paratenon using scanning electron microscopy. In
      the canine study, seven intrasynovial flexor digitorum profundus (FDP) tendons,
      seven extrasynovial fibularis (peroneus) longus (FL) tendons with paratenon, and
      seven FL tendons without paratenon were used. In the human study, seven
      intrasynovial FDP tendons and seven extrasynovial palmaris longus (PL) tendons
      cut in half (one half with paratenon, the other half without paratenon) were
      used. The gliding resistance of each tendon was measured at 1, 5, 10, 20, 50,
      and100 flexion/extension cycles. The canine and human FDP tendons maintained a
      gliding resistance significantly lower than that of the other tendons at all
      observation points (P < 0.05). In the canine, the gliding resistance of the FL
      tendon with paratenon was significantly lower than that of the FL tendon without
      paratenon up to 50 flexion/extension cycles (P < 0.05), but the two were not
      significantly different at 100 cycles. In the human, the gliding resistance of PL
      tendons with paratenon was significantly lower than that of the PL tendons
      without paratenon at all measuring points (P < 0.05). Preservation of paratenon
      thus appears to decrease the gliding resistance of extrasynovial tendons after
      repetitive motion in vitro.

PMID- 11948956
TI  - Dual innervation of the brachialis muscle.
AB  - A study of the innervation of the brachialis muscle was carried out on 45 male
      and 31 female Thai cadavers between the ages of 15 and 92 years (mean = 59
      years). The dissections revealed that all brachialis muscles received innervation
      from the musculocutaneous nerve and that 81.6% were also innervated by a branch
      from the radial nerve. Among the brachialis muscles with a dual nerve supply, two
      patterns of branching from the radial nerve were observed: in one pattern the
      branch to the brachialis had a descending course (58%) and in the other pattern
      the nerve ascended or recurred (42%) to innervate the muscle. The radial nerve
      branch penetrated the inferolateral part of the brachialis muscle in 83% of cases
      (103/124) and its middle third in 17% of specimens (21/124). The basis for the
      dual innervation may result from fusion of two different embryonic muscular
      primordia: the ventral (flexor) and the dorsal (extensor) muscle masses. In
      contrast to a brachialis muscle innervated by the musculocutaneous nerve only, a
      muscle with dual innervation may be spared significant denervation by an anterior
      approach to the humerus through a longitudinally bisected muscle. In a dually
      innervated muscle, however, separation of the brachialis and brachioradialis
      muscles during surgery may put the radial nerve branch to the brachialis at risk.

PMID- 11948957
TI  - Triangular structure of the proximal femur.
AB  - The normal human skeleton is remarkably regular in form. Its constancy is
      demonstrated by the projection of well-recognized lines onto plain radiographs to
      define many of its relationships. The finding of the geometric symmetry of the
      normal proximal femur, demonstrated by the projection of an isosceles triangle
      onto its anteroposterior radiographic view, is presented. The base of this
      triangle extends between the trochanters and its apex lies at the center of the
      femoral head. This triangle may reflect the balance of bone modeling that takes
      place in the proximal femur as a result of the forces acting in the coronal
      plane. If so, it may then allow for the development of a mathematical expression
      for bone modeling in this plane.

PMID- 11948958
TI  - Insertion of the tendon of the tibialis anterior muscle in feet with and without
      hallux valgus.
AB  - The insertion of the tendon of the tibialis anterior muscle may be related to
      pathologic changes of the foot and, in particular, hallux valgus. Morphologic
      data should enable evaluation of such a relationship and perhaps offer a basis
      for improved therapy. One hundred fifty-six embalmed feet, including 27 with
      hallux valgus, were examined. The tendon of the tibialis anterior muscle was
      dissected and measurements were made, including the width of the insertion on the
      first metatarsal and medial cuneiform. Distal-superficial and proximal-deep slips
      of the tendon twisted around each other. Two specimens presented with an
      insertion only on the medial cuneiform; in two other cases the insertion was
      limited to the first metatarsal; in one case the tendon inserted into the
      navicular and the medial cuneiform; in all other cases, the tendon inserted into
      the medial cuneiform and first metatarsal. The insertion was mainly located along
      the plantar margin of the medial side of the foot; some of the proximal-deep
      fibers also passed onto the plantar surface. Fibers inserting on the first
      metatarsal bone can outwardly rotate the first ray, which is opposite to the
      inward rotation of the first ray in hallux valgus. In all feet with hallux valgus
      these fibers were present. Therefore, it is unlikely that this deformity develops
      because of a specific type of insertion of the tendon of the tibialis anterior
      muscle, and any therapeutic approach altering the attachment of the tibialis
      anterior tendon would cause no biomechanical improvement.

PMID- 11948959
TI  - Unique case of trifurcation of the brachial artery: its clinical significance.
AB  - The variability of the arteries in the upper extremity is considerable. This case
      is a report of a trifurcation of the brachial artery that divided into radial,
      ulnar, and superior ulnar collateral arteries high in the arm; the length of the
      brachial artery was only 4.9 cm. Because the upper extremity is a frequent site
      of injury, various surgical and invasive procedures are performed in this region;
      consequently, it is of utmost importance to be aware of arterial variations. For
      some medical procedures, there may be an increased risk of complications because
      of variant vessels; however, for other procedures, they may be beneficial. In
      addition to presenting a detailed anatomic study of the case, the clinical
      significance of the variation has been addressed.

PMID- 11948960
TI  - Clinical anatomy research in a research-driven anatomy department.
AB  - Clinical anatomy is too often viewed as a discipline that reiterates the wisdom
      of the past, characterized more by description of what is known than by active
      investigation and critical analysis of hypotheses and ideas. Various
      misconceptions follow from an acceptance of this premise: the teaching of
      clinical anatomists is textbook based, there is no clinical anatomy research
      worthy of the name, and any research that does exist fails to utilize modern
      technology and does not stand comparison with serious biomedical research as
      found in cell and molecular biology. The aim of this paper is to challenge each
      of these contentions by reference to ongoing clinical research studies within
      this department. It is argued that all teaching (including that of clinical
      anatomy) should be research-informed and that the discipline of clinical anatomy
      should have at its base a vigorous research ethos driven by clinically related
      problems. In interacting with physicians, the role of the clinical anatomist
      should be to promulgate a questioning scientific spirit, with its willingness to
      test and challenge accepted anatomic dicta.

PMID- 11948961
TI  - Horizontal and vertical integration of academic disciplines in the medical school
      curriculum.
AB  - A rapid expansion of new scientific information and the introduction of new
      technology in operative and diagnostic medicine has marked the last several
      decades. Medical educators, because of and parallel to these developments,
      initiated a search for a more effective system of presenting core material to
      medical students. The new educational trends, although varying somewhat from one
      institution to another, concentrated on the following pedagogical shifts: 1)
      expansion of conceptual presentation of material at the expense of detail
      oriented education; 2) amplification of an integrated approach, as opposed to
      subject-oriented instruction; 3) scheduling of elective courses to compliment
      required courses in the curriculum; and 4) institution of small group instruction
      (i.e., problem-based learning) to actively involve students in the educational
      process and to develop deductive reasoning based on clinical cases. The future
      pedagogical system in medical schools will most likely be a combination of
      "classical" presentation of material combined with concept-oriented, subject
      integrated and small group instruction based on either hypothetical or real
      clinical cases. It is imperative for the success of the new curriculum, however,
      that certain criteria are satisfied: 1) reorganize basic science departments to
      determine course ownership; 2) establish a reward system for teaching faculty;
      and 3) establish new course objectives.

PMID- 11948962
TI  - Growth inhibition of prostate cancer xenografts by halofuginone.
AB  - BACKGROUND: Halofuginone, an inhibitor of collagen type I synthesis, is an anti
      angiogenic agent. Here we evaluated the efficacy of halofuginone to inhibit
      prostate cancer (PC) xenografts representing various phenotypes of the disease.
      METHODS: An androgen-dependent (CWR22), an androgen-independent (PC3), and a
      neuroendocrine (WISH-PC2) PC xenograft were used. Halofuginone was given orally
      or injected intraperitoneally. Tumor size, collagen alpha1(I) gene expression (in
      situ hybridization), collagen content (sirius red staining), angiogenesis
      (immunohistochemistry with factor VIII antibodies), and apoptosis/necrosis (DNA
      fragmentation) were evaluated. RESULTS: Halofuginone inhibited the growth of all
      subcutaneously implanted xenografts and of WISH-PC2 when transplanted
      orthotopically. The effect was dose-dependent (WISH-PC2) and accompanied by
      decrease in plasma PSA levels (CWR22). In all xenografts, halofuginone inhibited
      collagen alpha1(I) gene expression, reduced collagen content, and endothelial
      cell number resulting in an increase in apoptosis/necrosis. CONCLUSIONS: Oral
      administration of halofuginone slowed the progression of PC xenografts
      representing a broad range of phenotypes. Halofuginone may become a new modality
      for PC prevention.

PMID- 11948963
TI  - Elevated serum progastrin-releasing peptide (31-98) in metastatic and androgen
      independent prostate cancer patients.
AB  - BACKGROUND: Increases in neuroendocrine phenotype and secretory products are
      closely correlated with tumor progression and androgen independence in prostate
      cancer. In this study, we explored this correlation using serum progastrin
      releasing peptide (ProGRP), a carboxy-terminal region common to three subtypes of
      precursors for gastrin-releasing peptide (GRP), which is released from the
      neuroendocrine phenotype to act as a growth factor. METHODS: In 60 patients with
      benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP
      levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit and
      evaluated in relation to clinical stage, hormonal treatment, and prostate
      specific antigen (PSA) values. Fourteen randomly selected patients were entered
      in the follow-up study. Additionally, expression of ProGRP as determined by
      immunohistochemical analysis was compared to that of chromogranin-A (CgA) in
      tissue samples from several subjects. RESULTS: We found a positive correlation
      between PSA and ProGRP in patients with untreated prostate cancer; no correlation
      was found in the treated groups. The increases in the ProGRP value and in the
      percentage of patients with higher than normal values were significant (P <
      0.0001), especially in the androgen-independent group (P < 0.0001). A
      longitudinal study showed that, in a subset of patients, the ProGRP values tended
      to increase transiently when the cancer became androgen independent, but remained
      unchanged or decreased at the androgen-dependent stage. Positive staining for
      ProGRP occurred in a different distribution in neuroendocrine tissues than that
      of staining for CgA. CONCLUSIONS: The clinical results demonstrated the existence
      of a regulatory mechanism for GRP, which to date had only been observed in cell
      lines. These findings suggest that GRP is a growth factor potentially upregulated
      by androgen but that does not rely principally on androgen modulation. The large
      overlap in levels of ProGRP among the groups limits the use of this value as a
      monitoring tool. Measurement of ProGRP, however, does have potential as an
      independent parameter to evaluate androgen-independent progression and to
      facilitate a new therapeutic strategy that may compensate for current limitations
      of diagnosis based on PSA alone.

PMID- 11948964
TI  - Intermediate cells in normal and malignant prostate epithelium express c-MET:
      implications for prostate cancer invasion.
AB  - BACKGROUND: Analysis of keratin (K) expression discriminates luminal (K18) and
      intermediate (K5/18) cells in prostate carcinoma, while basal (K5/14) cells are
      absent. Intermediate cells have been proposed as targets of malignant
      transformation in prostate cancer and precursors of androgen-independent tumor
      progression. We demonstrate localization of hepatocyte growth factor (HGF)
      receptor c-MET in intermediate cells in both normal and malignant prostate
      epithelium. METHODS: Receptor localization was analyzed using triple staining for
      c-MET, K5, K14, and K18. The percentage of strongly c-MET positive cells was
      determined in 15 prostate cancer patients undergoing androgen-deprivation and 14
      patients without neo-adjuvant treatment. Effects of HGF were investigated on
      prostate cancer cell line DU145. RESULTS: c-MET expression in non-malignant
      epithelium was strong in intermediate cells absent in differentiated cells, and
      heterogeneous in basal cells. In prostate cancer, intermediate cells displayed
      high c-MET levels coupled with mild expression in differentiated cells. During
      androgen-deprivation, 7.6% of tumor cells revealed high c-MET expression compared
      to 1.7% without treatment (P = 0.02). Matrigel penetration of DU145 was 8.2 +/-
      1.7 mm(2) after HGF stimulation compared to 3.6 +/- 2.4 mm(2) in controls (P <
      0.02). CONCLUSIONS: Intermediate cells in normal and malignant prostate
      epithelium express high c-MET levels, indicating that they are prone to stromal
      invasion in prostate carcinoma.

PMID- 11948965
TI  - Expression of peroxisome proliferator-activated receptor (PPAR) in human prostate
      cancer.
AB  - BACKGROUND: Recent studies have demonstrated that peroxisome proliferator
      activator-receptors (PPAR)-gamma is expressed in some cancer cells such as
      breast, lung, and gastric cancer, and its ligand induces growth arrest of these
      cancer cells through apoptosis. However, the expression and localization of PPARs
      in prostate have not been examined. In this study, PPARs expression was
      investigated in human prostate cancer (PC), prostatic intraepithelial neoplasia
      (PIN), benign prostatic hyperplasia (BPH), and normal prostate (NP) tissues.
      METHODS: Tumor specimens were obtained from 156 patients with PC, 15 with PIN, 20
      with BPH, and 12 patients with NP tissues. The expressions were investigated by
      RT-PCR and immunohistochemical methods. RESULTS: Immunoreactive PPAR-alpha and 
      beta were significantly apparent in PC tissues. Marked expressions of PPAR-alpha
      and -beta were also detected in PIN, BPH, and NP groups. However, very weak or no
      expression of immunoreactive PPAR-gamma was found in BPH and NP cases. In
      contrast, we found significant expression of immunoreactive PPAR-gamma in cancer
      cells in PC group and in PIN group. CONCLUSIONS: Our results demonstrated that
      PPAR-gamma is induced in PC, and suggest that PPAR-gamma ligands may mediate its
      own potent antiproliferative effect against PC cells through differentiation.

PMID- 11948966
TI  - Androgen ablation promotes neuroendocrine cell differentiation in dog and human
      prostate.
AB  - BACKGROUND: Mechanisms triggering prostatic NE differentiation are poorly
      understood. Since dog and man naturally develop prostatic proliferative diseases
      with age, our objectives were to confirm the presence of NE cells in the dog
      prostate and test their hormonal regulation in both species. METHODS: Serotonin
      staining was examined by immunohistochemistry in 37 dog prostates: 17 from intact
      and 20 from castrated animals. In intact dogs, 9 prostates were normal and 8
      hyperplastic. In the castrated group, 6 dogs were left untreated while androgens
      and estrogens were administered to 7 dogs, each. Human prostates were from 48
      prostate cancer patients; half of them were submitted to androgen ablation prior
      to prostatectomy. The density of serotonin-positive NE cells was expressed
      relatively to the number of acini. RESULTS: Serotonin-positive NE cells were
      morphologically similar in dog and human prostates and identified in all groups,
      independent of the hormonal status. NE cell densities were within the same range
      in normal and hyperplastic dog prostates but significantly higher after
      castration. Androgens and estrogens after castration restored NE cell density to
      normal values and induced luminal differentiation and basal metaplasia,
      respectively. In human, the density of serotonin-positive NE cells was also
      significantly higher in benign glands after androgen ablation. CONCLUSIONS: The
      dog is a suitable animal model and mimics the human, since androgen ablation
      favored prostatic NE differentiation in both species. The down-regulation
      elicited by steroids suggests that the process may be reversible and hormonally
      repressed.

PMID- 11948967
TI  - Down-regulation of the human kallikrein gene 5 (KLK5) in prostate cancer tissues.
AB  - BACKGROUND: Kallikreins are a subgroup of serine proteases with diverse
      physiological functions. Many kallikrein genes are differentially expressed in
      various malignancies and prostate specific antigen (PSA; encoded by the KLK3
      gene) is the best tumor marker for prostate cancer. Human glandular kallikrein
      (hK2; encoded by the KLK2 gene) is an emerging tumor marker for prostate cancer.
      KLK5 is a newly discovered human kallikrein gene which shares a high degree of
      homology and is located adjacent to KLK2 and KLK3 genes on chromosome 19q13.4.
      Like KLK2 and KLK3, the KLK5 gene is regulated by steroid hormones in the BT-474
      breast cancer cell line. We have previously shown that KLK5 is differentially
      expressed in ovarian and breast cancer. METHODS: We compared the expression of
      KLK5 in 29 pairs of histologically confirmed normal and prostate cancer tissues
      by quantitative RT-PCR using the LightCycler technology. RESULTS: KLK5 expression
      was significantly lower in cancer tissues compared to their normal counterparts.
      Lowest levels of expression were found in T3 stage tumors compared with T1 and
      T2. Also, a significant negative correlation was found between Gleason score and
      KLK5 expression. CONCLUSIONS: KLK5 should be further studied as a potential new
      prognostic marker in prostate cancer, whose expression is negatively correlated
      with cancer aggressiveness.

PMID- 11948968
TI  - Inhibitors of apoptosis proteins in prostate cancer cell lines.
AB  - BACKGROUND: The caspases are the central executioners of apoptosis. The
      inhibitors of apoptosis proteins (IAPs) are a family of recently described
      caspase inhibitors. We hypothesised that tumor resistance to apoptosis could be
      due in part to IAP expression. METHODS: The expression of NAIP, cIAP-1, cIAP-2,
      XIAP, and survivin was investigated in the prostate cancer cell lines LNCaP, PC3,
      and DU145. RNase protection assays and Western blotting were used to assess RNA
      and protein expression. Apoptotic susceptibility was determined using etoposide
      and assessed by propidium iodide (PI) DNA incorporation using flow cytometry.
      RESULTS: DU145 and PC3 cells were more resistant to apoptosis than LNCaP cells.
      All the IAPs were identified in the cell lines with variation in IAP expression
      between different cell types. Immunohistochemistry demonstrated cIAP-1 expression
      in PC3 cells was nuclear, while the expression of cIAP-2 and XIAP was
      perinuclear. Growing LNCaP cells in charcoal-stripped or androgen-supplemented
      medium resulted in no alteration in IAP expression. CONCLUSIONS: This study
      characterises the expression of IAP in three of the most commonly used prostate
      cancer cells. IAP may make an important contribution to apoptotic resistance in
      patients with prostate cancer.

PMID- 11948969
TI  - Insulin-like growth factor binding protein-3 induces early apoptosis in malignant
      prostate cancer cells and inhibits tumor formation in vivo.
AB  - BACKGROUND: Insulin-like growth factor binding protein (IGFBP-3) levels are
      significantly reduced in malignant prostate epithelial cells. In this study, we
      evaluated the role of endogenous IGFBP-3 on prostate cancer cell growth and
      tumorigenesis. METHODS: IGFBP-3 was re-expressed by stable transfection of human
      IGFBP-3 cDNA in a model of human prostate cancer, M12, a malignant subline in
      which IGFBP-3 levels are undetectable in comparison to the parent epithelial
      cell, P69. Effect of IGFBP-3 re-expression (M12-BP-3) on growth kinetics,
      morphology, propensity to apoptosis, and in vivo tumor formation were studied.
      RESULTS: M12-BP-3 cells secreted IGFBP-3 and growth arrested at a cell density
      that was threefold lower than control cells and this was associated with marked
      alteration in cell morphology. Control cells when grown in conditioned media
      secreted by M12-BP-3 also showed altered morphology compared to when cultured in
      IGFBP-3-immunodepleted conditioned media. The M12-BP-3 clones showed altered
      mitochondrial membrane potential, increased PARP cleavage, increase in sub-G1
      peak, decreased levels of neuron specific enolase, and decreased tumor formation
      in athymic, nude mice. CONCLUSIONS: These data suggest that IGFBP-3 induces early
      apoptosis and has potential tumor suppressive effect in prostate cancer. Prostate
      51: 141-152, 2002.

PMID- 11948970
TI  - Effect of the synergist, piperonyl butoxide, on the development of deltamethrin
      resistance in yellow fever mosquito, Aedes aegypti L. (Diptera: Culicidae).
AB  - The larvae and adults of Aedes aegypti were tested for the potential to develop
      resistance to the synthetic pyrethroid, deltamethrin, alone or a combination of
      deltamethrin with the synergist, piperonyl butoxide (PBO). Although continuous
      larval selection for 40 generations resulted in 703-fold resistance, the
      resistance ratio in the adults was only 1.3. Similarly, adult selections with
      deltamethrin showed a resistance ratio of less than four after 40 generations,
      indicating differential response to deltamethrin selection in the two
      developmental stages of the insect. When the susceptible larvae were subjected to
      selection pressure of deltamethrin and PBO in the ratio of 1:5 for 20
      generations, the speed of selection for deltamethrin resistance slowed down by
      60%. The F24 larvae obtained from the strain selected with deltamethrin alone
      were further subjected to selection pressure with synergized deltamethrin, which
      resulted in 89% reversal in deltamethrin resistance in just one generation.
      However, long-term selection with the insecticide-synergist combination returned
      resistance close to original levels in 15 generations. The data indicate the
      involvement of cytochrome P450-dependent detoxification as the primary mechanism
      of development of resistance to deltamethrin in the larvae. Implications of the
      results on the management of larval and adult stages of Ae. aegypti are
      discussed.

PMID- 11948971
TI  - Changes of protein tyrosine phosphorylation in third instar larval integument of
      the Mediterranean fruit fly, Ceratitis capitata.
AB  - Developmental analysis of the tyrosine protein phosphorylation levels in larval
      integument and partial characterization of the endogenous protein tyrosine kinase
      activity (PTK) in Ceratitis capitata are described in this study. Larval
      integument contains high levels of PTK activity at the early stages of the third
      instar, which progressively declines to low levels in the white pupal stage. An
      integumental 90-kDa polypeptide was identified to have prominent endogenous PTK
      activity and follow a similar developmental pattern. The major integumental
      phosphotyrosine-containing polypeptides have apparent molecular weights of 30,
      41, 44, 46, and 54 kDa, respectively. Polypeptides with molecular weights of 62
      and 73 kDa were identified as Ser/Thr-containing phosphoproteins and were shown
      to exhibit high levels of phosphorylation at the middle stage of larval
      development. These differences are likely to be due to the higher activation
      state of the protein tyrosine kinase(s) at the early stages of larval
      development.

PMID- 11948972
TI  - Endogenous control of circadian rhythms of pheromone production in the turnip
      moth, Agrotis segetum.
AB  - The circadian variation of pheromone production in the turnip moth, Agrotis
      segetum, was characterized by quantifying (Z)-7-dodecenyl acetate (Z7-12:OAc),
      the most abundant pheromone component produced by female turnip moth, at
      different times of day. Under 17:7 h light-dark cycle (LD), the peak of Z7-12:OAc
      production occurred around 4 h into the scotophase, while there was very little
      pheromone production during the photophase. When females were maintained under
      constant darkness (DD), the periodicity of pheromone production was sustained for
      3 consecutive days. Furthermore, the rhythm in pheromone production could be
      entrained to a shifted LD. These results demonstrate that the pheromone
      production in the turnip moth is regulated endogenously by a circadian clock. To
      understand how the circadian rhythm of pheromone production is generated,
      circadian variation of pheromone- biosynthesis-activating neuropeptide (PBAN)
      like activity in the brain-suboesophageal ganglion complexes (Br-SOG), hemolymph,
      and ventral nerve cord (VNC) was also examined. Under both LD and DD, only the
      VNC displayed a circadian variation in the PBAN-like activity, which was
      significantly higher during the late-photophase than that in the scotophase. In
      addition, the present study showed that removal of VNC in isolated abdomen did
      not affect PBAN stimulation of pheromone production, while severing the VNC
      impaired normal pheromone production. The role of Br-SOG, VNC, and hemolymph in
      the regulation of the periodicity of pheromone production is discussed.

PMID- 11948973
TI  - Perturbed turnover of microtubule-based nutritive tubes in ovarioles of virgin
      and precocene-treated Dysdercus fasciatus.
AB  - During early oogenesis in Dysdercus fasciatus, anteriorly positioned nurse cells
      supply each oocyte with mRNA, ribosomes, and proteins via a microtubule-rich
      nutritive tube that lengthens as the oocyte is displaced backwards down an
      ovariole. Nurse cell-dependent development of an oocyte continues until the
      latter reaches a particular stage of oogenesis after which the nutritive tube
      supplying it becomes redundant and breaks down. The signal for nutritive tube
      breakdown is believed to derive from the oocyte, and to be developmental stage
      specific. To explore this, nutritive tube turnover has been investigated
      following the experimental inhibition of oocyte maturation both by the prevention
      of mating, and also the topical application of precocene II. In each case, the
      nutritive tubes with their component microtubules continued to extend and failed
      to show normal tube redundancy, typified by microtubule rearrangement and then
      depolymerisation. This provided an in vivo demonstration that the dynamics of a
      large microtubule aggregate are influenced by the developmental state of the
      cytoplasm.

PMID- 11948974
TI  - Stimulation of trehalose efflux from cockroach (Periplaneta americana) fat body
      by hypertrehalosemic hormone is dependent on protein kinase C and calmodulin.
AB  - Protein kinase C and calmodulin play key roles in cockroach fat body during
      activation of phosphorylase and trehalose efflux by HTH-II. The data support the
      view that an increase in cytosolic Ca2+ is prerequisite for enhanced activity of
      protein kinase C and calmodulin. Chelation of Ca2+ (i) with BAPTA blocks HTH-II
      induced trehalose efflux from the fat body whereas thapsigargin, which raises
      [Ca2+]i to the same level as HTH-II, produces only a small, yet significant
      increase in trehalose efflux. Sphingosine, an inhibitor of protein kinase C,
      inhibits HTH-II-induced trehalose efflux in a concentration-dependent manner.
      Trehalose efflux is not activated by the protein kinase C activators OAG or PMA
      alone but in the presence of thapsigargin both agents increase trehalose efflux
      to a level comparable to that obtained with HTH-II. Thapsigargin has only a
      moderate activating effect on phosphorylase but in combination with OAG produces
      an activation indistinguishable from that provoked by HTH-II. Each of the
      structurally different calmodulin inhibitors, trifluoperazine, W-7, and
      calmidazolium, blocks completely the action of HTH-II on trehalose efflux, thus
      confirming the importance of calmodulin in HTH-II initiated trehalose efflux.

PMID- 11948975
TI  - Transition in cystic fibrosis: much ado about nothing? A pediatrician's view.

PMID- 11948976
TI  - Transition programs in cystic fibrosis centers: perceptions of patients.
AB  - There is a growing population of adults with cystic fibrosis (CF) and a need for
      development of adult CF programs. Recommendations for transfer of patients from
      pediatric care to an adult program include a transition program. The purpose of
      this study was to survey adult CF patients to assess their own concerns regarding
      this issue. A survey was sent to all 1,288 members of the International
      Association of Cystic Fibrosis Adults (IACFA), with a response rate of 25.9% (n =
      334). The majority of patients (81.2%) received care from a CF center; the major
      difference between those seen at a CF center and those seen at another facility
      was proximity to a CF center. Nearly one-fourth of patients seen at a CF center
      continued to receive care from a pediatrician even though a CF-trained internist
      was available; though these patients were younger, their mean age was still about
      30 years. Patients seen by a pediatrician were more like to be students and to
      live with their parents. Those patients seen in an adult program described a
      variety of criteria for their transfer to the adult pro-gram, but there were no
      consistent findings to suggest a standard transition program. Indeed, many
      patients did not meet the adult team until the time of the transfer. Most
      importantly, the patients reported their level of concern about transfer as
      minimal, far less than what CF physicians had perceived. These differences may
      impede the successful transition of patients into an adult program.

PMID- 11948977
TI  - Correlation between digital clubbing and pulmonary function in cystic fibrosis.
AB  - The correlation between digital clubbing and certain pulmonary function
      derangements (hypoxemia and FEV(1)) was previously described. However, the
      relationship between digital clubbing and other measures of pulmonary function or
      the presence of liver disease in patients with cystic fibrosis (CF) is poorly
      defined. Hence we compared the digital clubbing index (CI: ratio of distal
      phalangeal depth to interphalangeal depth) of 100 patients with CF (43 males, 57
      females; mean age, 15.7 +/- 7.3 years) with that of 100 age- and gender-matched
      healthy controls. Digital clubbing was defined as a CI > or = 1.00 (mean + 2.6
      SD; 99% of normal subjects). The CI and its relationship to pulmonary function
      and to liver disease was then evaluated in the CF patients. Digital clubbing was
      present in 75/100 (75%) of CF patients but was absent in all controls (P <
      0.0001). In CF patients, CI was inversely correlated with PaO(2) (r = -0.555; P <
      0.001), FEV(1) (r = -0.499; P < 0.001), and FEF(25-75%) (r = -0.404; P < 0.001),
      and was positively correlated with RV (r = 0.285; P < 0.05) and the slope of
      phase 3 of single-breath nitrogen washout (SP3N(2)) (r = 0.532; P < 0.01). There
      was no significant correlation between CI and age (r = 0.020; P = 0.84), TLC (r =
      -0.097; P = 0.34), PaCO(2) (r = 0.167; P = 0.10), or history of liver disease (P
      = 0.08). We conclude that in CF, the degree of digital clubbing is related to
      degree of hypoxemia, airways obstruction, hyperinflation, and nonuniformity of
      ventilation.

PMID- 11948978
TI  - Respiratory syncytial virus bronchiolitis: disease severity, interleukin-8, and
      virus genotype.
AB  - In infants with respiratory syncytial virus (RSV) bronchiolitis, we investigated
      whether disease severity is associated with the genotype of the infecting virus,
      or with the infant's immunological response to the infection, as determined by
      measurement of interleukin-8 mRNA in the nasopharyngeal aspirate. This was a
      cross-sectional observational study, performed in the Accident and Emergency
      Department, wards, and Intensive Care Unit of a large pediatric hospital.
      Participants included 276 infants with respiratory syncytial virus infection.
      Outcome variables included: disease severity (infants requiring oxygen or
      ventilation were classified as having severe disease); RSV virus genotype
      (determined according to typing scheme based on the nucleoprotein and G
      glycoprotein genes); and amount of interleukin-8 mRNA in the nasopharyngeal
      aspirate, as measured by a semiquantitative polymerase chain reaction assay. This
      was corrected for the amount of cellular material in the sample by expressing it
      relative to mRNA for a constitutively expressed gene, HGPRT. We found a highly
      significant association between the ratio of interleukin-8 mRNA/HGPRT mRNA in the
      nasopharyngeal aspirate and the occurrence of severe disease. Odds ratio per unit
      increase of interleukin-8 mRNA/HGPRT mRNA was 1.15 (95% CI, 1.06, 1.24), P =
      0.0004. There was no association between virus genotype and either disease
      severity or amount of interleukin-8 mRNA/HGPRT mRNA. In conclusion, there is a
      strong, dose-related association between interleukin-8 mRNA produced locally in
      the airways and disease severity, and a lack of association with virus genotype.
      This suggests that clinical manifestations of respiratory syncytial virus
      bronchiolitis are determined by local immunological responses to infection,
      rather than by characteristics of the infecting virus.

PMID- 11948979
TI  - Exhaled nitric oxide at school age in prematurely born infants with neonatal
      chronic lung disease.
AB  - Prematurely born infants with neonatal chronic lung disease (CLD) have increased
      respiratory morbidity and bronchial obstruction at school age. To evaluate the
      possible inflammatory basis of lung function abnormalities, we studied 40
      children, 7.5-9.6 years of age, born very prematurely (birth weights, 600-1,575
      g) and 14 nonatopic term-born controls, using flow-volume spirometry and exhaled
      nitric oxide (eNO) measurements. In children born prematurely, eNO was
      significantly higher in atopics than in nonatopics (respective means, 14.8 vs.
      6.3 ppb, P = 0.02). Nonatopic prematurely born infants did not differ
      significantly from controls (means, 6.3 vs. 6.4 ppb, P = ns). Of the 27 nonatopic
      children not on regular glucocorticoid inhalations, 9 had a history of CLD.
      Spirometry indicated bronchial obstruction and values that were significantly
      lower in prematurely born infants with or without CLD than in controls, and they
      were lower in the CLD than the non-CLD group. However, no significant differences
      were observed in eNO levels between CLD, non-CLD, and control groups (means, 6.8,
      5.9, and 6.4 ppb, P = ns). In nonatopic schoolchildren born very prematurely and
      with a history of CLD, we found no evidence of airway inflammation associated
      with increased eNO concentrations. Neither were eNO levels associated with
      severity of chronic lung disease, as determined by conventional lung function
      tests. eNO levels were higher in atopic children born prematurely than in
      controls.

PMID- 11948980
TI  - Subcutaneous terbutaline in children with chronic severe asthma.
AB  - A continuous subcutaneous infusion of terbutaline (CSIT) was used to treat 8
      children with chronic severe asthma who continued to experience frequent
      symptoms, despite treatment with regular oral prednisolone. Five patients
      experienced a symptomatic improvement from CSIT, leading to a reduction in
      regular medication. Three patients did not experience any lasting benefit from
      CSIT. The most common side effects were related to the infusion site (bruising
      and local infection). CSIT may lead to an improvement in symptoms and a reduction
      in oral steroid dose in selected children with chronic severe asthma. These
      initial findings support the need for further controlled studies to evaluate the
      use of CSIT in severe childhood asthma.

PMID- 11948981
TI  - Effects of intrabronchial foreign body retention.
AB  - Unrecognized bronchial foreign bodies (Fbs) cause irreversible changes in the
      airways. However, the exact course of these changes is not well-known. We
      developed an animal model of bronchial obstruction to radiologically and
      histopathologically assess the development of postobstructive pulmonary changes.
      A piece of peanut was placed in the airways of 21 rabbits through a 2.5-mm rigid
      bronchoscope. Animals were divided into three groups (groups I-III) that were
      sacrificed on day 3,10, and 30 after Fb placement, respectively. Prior to
      sacrifice, since there were no differences between the groups prior to Fb
      placement, computerized tomography (CT) of the lung was taken, and the lungs were
      harvested for histologic analysis under light microscope. In group I, leukocyte
      infiltration around the bronchial wall (P = 0.0003) and edema (P = 0.0384) around
      the alveolar septa were the predominant histological findings. The CT scan was
      normal. In group II and group III, increased amounts of mononuclear cells and
      macrophage infiltration around the bronchial wall were observed (P = 0.0008, P =
      0.0409, respectively). There were no differences in presence of granuloma
      formation, emphysema, atelectasis, or thickness of alveolar septa among the three
      groups. The CT scan of group II showed consolidations plus minimal bronchial
      dilatation in the involved lung of the rabbits (P not significant). Bronchial
      cartilage destruction was seen in 4 out of 7 rabbits in group III (P = 0.0071).
      We conclude that 30-day retention of intrabronchial peanut caused bronchial
      cartilage destruction and fibrosis that were attributed as bronchiectatic changes
      in the airways of the lung parenchyma. Therefore, any case with suspected foreign
      body aspiration should be treated immediately to prevent possible irreversible
      changes of the lungs.

PMID- 11948982
TI  - Effect of pacifier use on oral breathing in healthy newborn infants.
AB  - We tested the hypothesis that the use of a pacifier may affect the ability of
      some term infants to maintain effective oral breathing during prolonged nasal
      occlusion. Three nasal occlusion tests without a pacifier and 3 with a pacifier
      were alternately carried out in 20 healthy term infants (age 2-5 days). Once the
      infant commenced oral breathing, nasal occlusion was continued for up to 90 sec
      (prolonged nasal occlusion), provided the infant did not start crying and that
      arterial oxygen saturation (SaO(2)) did not drop to < or = 80%. The response to
      nasal occlusion was considered maladaptive if oral breathing was accomplished
      with signs of upper airway obstruction. After nasal occlusion, the infants
      succeeded in starting oral breathing in all instances after a delay which was
      strongly correlated to the drop in SaO(2) (P < 0.001). Once the infants commenced
      oral breathing, 17/20 infants presented a maladaptive response to 62% of all
      tests without pacifier, whereas 10/20 infants presented a maladaptive response to
      30% of all tests with a pacifier in place (P < 0.001). Following prolonged nasal
      occlusion, 18 of 19 infants presented a maladaptive response to 84% of all tests
      without pacifier, whereas 12 of 19 infants presented a maladaptive response to
      41% of all tests with a pacifier in place (P < 0.001). Thus, after prolonged
      nasal occlusion with or without pacifier, the drop in mean SaO(2) from baseline
      values changed in accordance with an appropriate and maladaptive response (-4 +/-
      1 vs. -7 +/- 1; P < 0.001). We conclude that normal term infants often present
      with a maladaptive response to prolonged nasal occlusion. The use of a pacifier
      enhances the infant's ability to maintain a more adequate oral air flow.

PMID- 11948983
TI  - Noninvasive investigation of hepatopulmonary syndrome in children and adolescents
      with chronic cholestasis.
AB  - Early detection of hepatopulmonary syndrome (HPS) may be delayed because of
      invasiveness of the diagnostic procedures. In this pilot study, we prospectively
      investigated the usefulness of determining transcutaneous O(2) tension after 100%
      O(2) (TcPO(2)100) breathing using a transcutaneous hyperoxia test (THT) in 11
      children with chronic cholestasis and without primary cardiopulmonary disease.
      These patients also underwent alveolar-arterial O(2) gradient testing (AaDO(2))
      at an inspired oxygen fraction (FiO(2)) of 0.21, lung scintiscan, and contrast
      transthoracic echocardiography (TTE). Three of them had a liver transplantation
      because of the downhill course of their liver disease and respiratory status. THT
      transcutaneous O(2) tension at 21% FiO(2) (TcPO(2)21) was 75 +/- 13 mm Hg, and
      increased to 488 +/- 106 mmHg after 100% O(2) breathing (TcPO(2)100). Both mean
      values were not significantly different from those found in 8 age-matched
      controls (P = 0.9 and P = 0.5, respectively). However, one patient, in spite of
      her stable liver function, showed an abnormal TcPO(2)21 and TcPO(2)100 (45 mmHg
      and 210 mmHg, respectively). This same subject was also the only patient with
      abnormalities of AaDO(2) (54.2 mm Hg; normal value, < 20 mm Hg), lung scintiscan
      (brain/lung ratio of technetium-99 fixation (B/L SI) = 9, normal value < 1), and
      TTE, suggesting intrapulmonary vasodilatations and shunts. Given the clinical
      development of cyanosis and platypnea, all criteria for HPS were fulfilled, and
      timing of her liver transplantation was therefore accelerated. This resulted in
      HPS regression. In children with chronic cholestasis, repeated transcutaneous
      bedside measurements are a rapid and reliable noninvasive test for characterizing
      the severity of abnormal oxygenation, and may prove useful also in liver
      posttransplantation monitoring.

PMID- 11948985
TI  - Assessment of a low-cost home monitoring spirometer for children.
AB  - Electronic devices are now available to measure and store lung function
      parameters in the home. Before adopting a device for clinical or research use, it
      is important to validate it in the target patient group. The aim of this study
      was to assess a low-cost, portable, logging spirometer, the VM Plus (VM), against
      a standard laboratory Jaeger spirometer (JS) for use in children with respiratory
      disease. Seventy children with stable asthma or cystic fibrosis performed
      spirometry on the two devices, and results for peak expiratory flow (PEF) and
      forced expiratory volume in 1 sec (FEV(1)) were compared. Comparison was made
      both using the two devices separately (separate method) and with the devices
      connected in series (series method). Reproducibility of the VM measurements was
      also assessed. Correlation between measurements was close (R values: separate,
      PEF, 0.91; FEV(1), 0.94; series, PEF, 0.97, FEV(1), 0.99), but PEF readings on
      the VM Plus were substantially higher than with the JS (mean difference:
      separate, 54.8 L/min; series, 28.2 L/min). This reflects well-reported
      differences in PEF measurements between the Mini-Wright PEF meter, on which the
      VM Plus spirometer is based, and conventional spirometers. Limits of agreement
      (series method) were: PEF, -13.2 to +69.6 L/min; FEV(1), -0.03 to +0.19 L.
      Reproducibility of VM Plus measurements was acceptable: coefficient of variation
      for PEF was 4%; for FEV(1), 4.3%; coefficient of reproducibility for PEF, 39
      L/min; for FEV(1), 0.26 L. The VM Plus provides reasonably accurate, reproducible
      measurements of PEF and FEV(1), but intrinsic bias, particularly in PEF
      measurement, needs to be taken into account. Its potential to document
      longitudinal changes in lung function in children with respiratory disease at
      home merits further study.

PMID- 11948984
TI  - Assessment of inspiratory flow limitation in children with sleep-disordered
      breathing by a nasal cannula pressure transducer system.
AB  - A nasal cannula pressure transducer system identifies inspiratory flow limitation
      and increased upper airway resistance in adults with sleep-disordered breathing
      (SDB). The purpose of this study was to evaluate whether nasal cannula pressure
      (NCP) detects apneas and hypopneas as well as additional flow-limited events
      associated with increased airway resistance in children. We studied NCP in 47
      patients (ages 2-14 years) referred for SDB to a university-based sleep disorders
      program during nocturnal polysomnography (NPSG). During NPSG, airflow was
      assessed simultaneously by thermistor and NCP. There was a high correlation
      between apneas assessed by thermistor (T) and NCP (r = 0.90, P < 0.0001), and for
      hypopneas using these two methods (r = 0.94, P = 0.0001). Respiratory driving
      pressure was indirectly measured with an esophageal pressure catheter. Flow
      limited (flattened) NCP waves were associated with significantly higher driving
      pressure, indicating elevated upper airway resistance, compared to nonflow
      limited (rounded) waves during nonrapid eye movement (NREM) (P = 0.05) and rapid
      eye movement (REM) (P = 0.01) sleep. Patients were classified as either having
      obstructive sleep apnea syndrome (OSAS) or primary snoring, based on standard
      NPSG criteria. NCP identified additional respiratory events with a flattened
      contour (FC) not detected by thermistor. NCP is a noninvasive device that
      identifies obstructive apneas and hypopneas as well as additional respiratory
      events associated with flow limitation in children.

PMID- 11948986
TI  - Severe respiratory syncytial virus pneumonia associated with primary Epstein-Barr
      virus infection.
AB  - This is a case report of a child with severe respiratory syncytial virus (RSV)
      pneumonia and concurrent infection with Epstein-Barr virus. We hypothesize that
      immunosuppression due to EBV may have contributed to the severity of his RSV
      infection. The diagnosis of RSV infection was facilitated by bronchoalveolar
      lavage.

PMID- 11948987
TI  - Hodgkin's disease and ataxia telangiectasia with pulmonary cavities.
AB  - Ataxia telangiectasia (AT) homozygotes have an increased risk for development of
      Hodgkin's disease (HD). Parenchymal lung involvement is not uncommon in HD;
      however, cavitary pulmonary lesions are quite unusual. We report on 3 cases of AT
      with HD who had mediastinal disease and parenchymal pulmonary involvement with
      cavitation. Of 6 AT patients in our HD series, 3 developed pulmonary cavities.
      The patients displayed pulmonary infiltration, cavitation in the lung parenchyma,
      and mediastinal enlarged lymph nodes on both plain chest X-rays and thoracic
      computed tomographies. No infectious etiologies were established for the
      pulmonary findings. Histopathological examination of open lung and mediastinal
      biopsies revealed HD, and all patients received multiagent chemotherapies. The
      outcome was fatal in all 3 patients. Respiratory infections are the principle
      cause for morbidity and mortality in AT patients. Reports on cavitating pulmonary
      lesions in HD are quite rare. Furthermore, data regarding the patterns of
      pulmonary involvement in AT patients with or without HD are lacking. The
      increased incidence of malignancies in AT patients may relate to immunodeficiency
      and to the chromosomal alterations identified.

PMID- 11948988
TI  - Cystic fibrosis and infantile hypertrophic pyloric stenosis: is there an
      association?
AB  - Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasian
      populations. The generally accepted incidence of CF in the United States is 1 in
      3,200 in the Caucasian population. Intestinal obstructions and atresias have been
      described among patients with CF. An association of CF with infantile
      hypertrophic pyloric stenosis (IHPS) has not been previously documented. A review
      in our clinic of 72 patients with CF revealed IHPS in two. The incidence of 2.7%
      is greater than the 0.3% incidence expected in the general population. This
      ninefold increase in IHPS in patients with CF suggests an association between the
      two and warrants further investigation.

PMID- 11948989
TI  - Once-daily tobramycin monotherapy in cystic fibrosis.

PMID- 11948992
TI  - Preparing for the 2001 Texas Legislative session. Nurse staffing. What's
      adequate? What's safe?

PMID- 11948990
TI  - Once-daily tobramycin.

PMID- 11948993
TI  - BNE proposes revised delegation rules.

PMID- 11948995
TI  - Newborn auditory follow-up.
AB  - Because hearing is a key component in the infant's development of speech,
      language, and cognition, early detection of infant hearing loss is critically
      important. The routine evaluation of hearing should include the identification of
      parental concerns regarding infant hearing as well as the assessment and
      diagnosis of infants with potential hearing impairment. Identification of hearing
      loss should be followed by early interventions to prevent developmental delays.
      This article promotes universal screening of newborn hearing. The article also
      provides a review of the embryogenesis of hearing and includes a breakdown of
      risks for hearing loss, recommendations for auditory testing, and suggestions for
      follow-up, early intervention, and support for families of infants with hearing
      impairment.

PMID- 11948994
TI  - Saline for peripheral intravenous locks in neonates: evaluating a change in
      practice.
AB  - PURPOSE: To evaluate the efficacy of saline versus 10 units/ml heparin for
      peripheral i.v. flushes in neonates. DESIGN: A nonexperimental group design was
      used to compare the longevity of heparin and saline i.v. locks. A research
      utilization method was chosen to increase the study power while simultaneously
      implementing a practice change and evaluating the outcomes. Power analysis showed
      that a sample size of approximately 120 per group was needed to decrease the risk
      of beta error to 0.1. SAMPLE: Subjects included neonates in the Special Care
      Nurseries at a Level III large midwestern university teaching hospital. Data were
      collected from a convenience sample of 123 neonates receiving 10 units/ml heparin
      flush into a peripheral i.v. Practice was then changed to preservative-free
      normal saline, and data collection continued for 117 neonates. MAIN OUTCOME
      VARIABLE: I.v. catheter longevity. RESULTS: There was no significant statistical
      difference in i.v. catheter longevity between i.v. locks flushed with 10 units/ml
      heparin and those flushed with normal saline. Patient weight accounted for a
      significant proportion of the variance in i.v. catheter life.

PMID- 11948996
TI  - Radiology basics: overview and concepts. Introduction.

PMID- 11948997
TI  - Assessment of the quality of the neonatal chest x-ray film.

PMID- 11948998
TI  - How to evaluate lung fields on the neonatal chest x-ray film.

PMID- 11948999
TI  - Shoulder dystocia as one cause for perinatal asphyxia: a case study.

PMID- 11949000
TI  - Mixing laughter with learning, breastfeeding game covers the basics.

PMID- 11949001
TI  - Important drug warning: Immune Globulin Intravenous (human) (IGIV) products.

PMID- 11949002
TI  - Transdermal clonidine.

PMID- 11949003
TI  - Instituting developmental care: one unit's success story.

PMID- 11949004
TI  - The pituitary gland: embryology, physiology, and pathophysiology.
AB  - The pituitary gland, the "master gland" of the body, is composed of endocrine
      cells, which secrete hormones essential for homeostasis. The gland consists of
      the adenohypophysis (anterior pituitary) and the neurohypophysis (posterior
      pituitary), two unique structures that differ anatomically and functionally. The
      neurohypophysis is innervated by nerve cells in the hypothalamus and forms the
      connection between it and the pituitary gland. The hypothalamus stimulates
      release and inhibition of pituitary hormones. The neurohypophysis secretes
      oxytocin and antidiuretic hormone. The adenohypophysis is composed of three
      structures: the pars distalis, the pars intermedia, and the pars tuberalis. The
      anterior pituitary (pars distalis) is responsible for the release of hormones
      that include growth hormone, prolactin, thyroid-stimulating hormone, follicle
      stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, and
      melanocyte-stimulating hormone. Disorders of the pituitary are predominately
      those of insufficient hormone release and may have profound effects on the
      neonate. The potential causes of and clinical symptomatology that may accompany
      pituitary hormone insufficiency in the neonatal period are explored.

PMID- 11949006
TI  - TNA wins big for nursing in the 76th Texas Legislature.

PMID- 11949008
TI  - Nursing involvement in Health Policy Legislation.

PMID- 11949009
TI  - Is a serious nurse shortage coming?

PMID- 11949010
TI  - Alternative therapy: what's a nurse to do?

PMID- 11949011
TI  - Continuing nursing education and the CNE Committee.

PMID- 11949012
TI  - Disease management.

PMID- 11949013
TI  - End-of-life care series, Part 1. Improving care at the end of life: barriers,
      challenges and resources.

PMID- 11949014
TI  - Nurse staffing: are the answers emerging?

PMID- 11949015
TI  - End-of-life care: who needs it?

PMID- 11949016
TI  - Update--nurse workforce data project.

PMID- 11949017
TI  - Tomorrow's nurses: are we ready for them?

PMID- 11949018
TI  - BNE acts on recommendations of competency/jurisprudence task forces.

PMID- 11949019
TI  - Intraventricular hemorrhage in the term infant.
AB  - Intraventricular hemorrhage (IVH) in the term infant is an uncommon and
      unexpected diagnosis. This article examines the frequency of IVH in the term
      newborn; the pathogenesis behind IVH; the presentation according to the location,
      extent, and cause of the hemorrhage; the diagnosis, associated complications,
      management, and outcomes of infants with IVH; and nursing responsibilities. A
      case study is offered of a term infant who presented with seizures after a normal
      labor and delivery, was found to have bilateral Grade III hemorrhages, and
      proceeded to develop posthemorrhagic hydrocephalus. Her management and outcome to
      date are discussed.

PMID- 11949020
TI  - From breast to baby: quality assurance for breast milk management.
AB  - Breast milk is a body fluid capable of transmitting blood-borne pathogens when
      ingested. High-risk infants are frequently fed mother's expressed breast milk and
      may be at risk if they receive the wrong mother's milk. A multidisciplinary team
      at this 42-bed Level III regional NICU developed a quality assurance program and
      audit aimed at reducing the risk of feeding expressed breast milk (EBM) to the
      wrong high-risk infant in the unit. Changes to the old system included
      modernizing the handling, storing, and distribution of EBM. Elimination of
      feeding errors was the priority. A specific protocol to minimize EBM feeding
      errors became part of the quality assurance program and is consistent with the
      recommendations of the NICU multidisciplinary team.

PMID- 11949021
TI  - Pulmonary sequestration.

PMID- 11949022
TI  - Evaluation of periventricular-intraventricular hemorrhage in premature infants
      using cranial ultrasounds.

PMID- 11949023
TI  - Tearing and embolization of percutaneous central venous catheters.

PMID- 11949024
TI  - Neonatal tachyarrhythmias.

PMID- 11949025
TI  - Neonatal cortical hyperostosis.

PMID- 11949026
TI  - Neonatal resuscitation.

PMID- 11949027
TI  - Kangaroo care.

PMID- 11949028
TI  - Raising an NICU orientee.

PMID- 11949029
TI  - Recognizing leadership.

PMID- 11949030
TI  - Another whistle-blower victory.

PMID- 11949031
TI  - Professionalism: healing through LIGHT.

PMID- 11949032
TI  - Nurses at risk.

PMID- 11949033
TI  - Texas legislature passes bills on health care worker exposure to bloodborne
      pathogens.

PMID- 11949034
TI  - Staff models for the next millennium.

PMID- 11949036
TI  - [Better screening of abused children].

PMID- 11949039
TI  - [Asthma, still more progress to be made].

PMID- 11949040
TI  - [Should we vaccinate children against influenza?].

PMID- 11949041
TI  - [Organization of pediatric intensive care services].

PMID- 11949042
TI  - [Admission reception, it's the beginning of nursing care].

PMID- 11949043
TI  - [Admission process].

PMID- 11949044
TI  - [Admission personnel, the multidisciplinary team].

PMID- 11949046
TI  - [And if play writing is also therapeutic?].

PMID- 11949045
TI  - [Clinical care of bronchiolitis in infants. 2/2].

PMID- 11949047
TI  - [Quality assurance of a high school emergency team].

PMID- 11949048
TI  - [Bathing and care of the newborn infant].

PMID- 11949049
TI  - [Does there exist a right to not be born handicapped?].

PMID- 11949050
TI  - [Child death announcement, a "mine field" of grief. Interview by Brigitte Blond].

PMID- 11949051
TI  - [How to grieve a perinatal death?].

PMID- 11949052
TI  - [Nursing shortage and migrations, a world problem].

PMID- 11949053
TI  - Changing health care policy ... power sharing.

PMID- 11949055
TI  - Redefining confidentiality in an on-line world.

PMID- 11949056
TI  - End-of-life decisions: legal & ethical quandaries.

PMID- 11949057
TI  - Tamoxifen. To take or not to take. That is the question.

PMID- 11949058
TI  - The Texas State Board of Nurse Examiners.

PMID- 11949059
TI  - Momentum for strong workplace advocacy structure within ANA continues.

PMID- 11949060
TI  - Mothers' stories about their experiences in the neonatal intensive care unit.
AB  - The purpose of this article is to let mothers tell the stories of their neonatal
      intensive care unit (NICU) experiences and to determine how well these
      experiences fit the Preterm Parental Distress Model. Interviews were conducted
      with 31 mothers when their infants were six months of age corrected for
      prematurity and were analyzed using the conceptual model as a framework. The
      analysis verified the presence in the data of the six major sources of stress
      indicated in the Preterm Parental Distress Model: (1) pre-existing and concurrent
      personal and family factors, (2) prenatal and perinatal experiences, (3) infant
      illness, treatments, and appearance in the NICU, (4) concerns about the infant's
      outcomes, (5) loss of the parental role, and (6) health care providers. The study
      indicates that health care providers, and especially nurses, can have a major
      role in reducing parental distress by maintaining ongoing communication with
      parents and providing competent care for their infants.

PMID- 11949061
TI  - Physicians' neonatal resuscitation of extremely low-birth-weight preterm infants.
AB  - PURPOSE: To examine the perceptions of physicians who make delivery room
      decisions to resuscitate extremely low-birth-weight (ELBW) neonates at marginal
      viability. Nurses, parents, economists, and ethicists have questioned
      resuscitation of ELBW neonates, many of whom experience high levels of morbidity
      and mortality. Yet no systematic studies were found that addressed physicians'
      perceptions and delivery room decisions. DESIGN: Descriptive, using naturalistic
      inquiry. A national U.S. convenience sample was obtained in 1996-1997 of 54
      physicians in five perinatal subspecialties who resuscitated ELBW neonates.
      METHODS: Tape-recorded and transcribed interviews were analyzed using NUD*IST
      software and line-by-line constant comparison. FINDINGS: Despite awareness of the
      high morbidity and mortality, 96 percent of the physicians offered resuscitation
      to all ELBW neonates in the delivery room. The main factors affecting their
      decisions were "the role of the physician;" having been "trained to save lives;"
      the belief that "if called, I resuscitate;" the inability to determine
      gestational age; requests from parents to "do everything;" and the need to move
      from a "chaotic" delivery room to a controlled neonatal intensive care unit. Six
      major themes were: role expectation, uncertainty, awareness, internal and
      external forces, burden, and continuing quandaries. Physicians were burdened by
      the devastated and dying babies, by their inability to predict which neonates had
      a chance for intact survival, and by conflicts with colleagues about viability.
      Statistical probability of survival, legal constraints, and cost of care did not
      appear to affect greatly their decisions. Physicians asked that society and
      national policy makers set parameters for resuscitation. CONCLUSIONS: The
      American Academy of Pediatrics' Neonatal Resuscitation Protocol needs revision to
      delineate the ethical criteria for resuscitation. Early prenatal education for
      families which clearly teaches the margins of viability and outcomes of early
      deliveries is also recommended. Physicians must be supported in changing the
      resuscitation paradigm.

PMID- 11949062
TI  - Radiology basics, Part II: RDS and BPD.

PMID- 11949063
TI  - Chest x-ray findings in respiratory distress syndrome.

PMID- 11949064
TI  - Bronchopulmonary dysplasia.

PMID- 11949065
TI  - Case study: listeriosis in the neonate.

PMID- 11949066
TI  - Shaken baby syndrome: agenda setting at the state and local level.

PMID- 11949067
TI  - March of Dimes enlists professionals in fight against birth defects.

PMID- 11949068
TI  - Chest x-ray findings in arteriovenous malformation of the great vein of Galen.

PMID- 11949069
TI  - The pineal gland.
AB  - The pineal gland is located posterior to the midbrain and is the site of
      melatonin production. Research on pineal gland function in neonates is very
      limited. This article will discuss pineal gland development and the possible
      relationship between melatonin production and sudden infant death syndrome.
      Further research on pineal gland function is needed in order to establish its
      significance for the neonate.

PMID- 11949070
TI  - [The child is the beginning of the man].

PMID- 11949071
TI  - [Generalized management of neonatal mucoviscidosis].

PMID- 11949072
TI  - [Risks of dioxins on health are still poorly evaluated].

PMID- 11949073
TI  - [The child as a symptom of society].

PMID- 11949074
TI  - [We are all symptomatic children].

PMID- 11949075
TI  - [When the child becomes the carrier of the family symptom].

PMID- 11949076
TI  - [The "parentified" child, a concept of contextual approach].

PMID- 11949077
TI  - [The symptomatic child or the messenger].

PMID- 11949078
TI  - [An encounter group for HIV seropositive adolescents].

PMID- 11949079
TI  - [Sleep disorder, a message to decipher].

PMID- 11949080
TI  - [A breathing school for asthmatic children].

PMID- 11949081
TI  - [Sophrology and the child].

PMID- 11949082
TI  - [Gluten intolerance. Celiac disease].

PMID- 11949083
TI  - [Recommendations for managing bronchiolitis in the infant].

PMID- 11949084
TI  - [Best indications for cesarean section].

PMID- 11949085
TI  - [Improving access to contraception and voluntary pregnancy termination].

PMID- 11949086
TI  - Workplace advocacy.

PMID- 11949087
TI  - End-of-life series, Part 3. Working with dying patients: caregivers need support
      too!

PMID- 11949088
TI  - South Texas nurses address area needs.

PMID- 11949089
TI  - Job satisfaction affects nursing supply. Workplace practices create
      dissatisfaction.

PMID- 11949090
TI  - Nursing and the legislative process: a successful outcome.

PMID- 11949091
TI  - Spit Tobacco Prevention Network (STOPN).

PMID- 11949092
TI  - To err is human: IOM report implications.

PMID- 11949093
TI  - Spirituality and the nurse.

PMID- 11949094
TI  - Spiritual turn-arounds.

PMID- 11949095
TI  - Looking to the future: health professions education in Texas.

PMID- 11949096
TI  - Creating change in nursing education....

PMID- 11949097
TI  - Texas' nursing education system. Can it respond to this nursing shortage?

PMID- 11949098
TI  - Pancreatic disorders in the newborn.
AB  - Except for the hyperinsulinism associated with the infant of a diabetic mother
      (accounting for about 5 percent of NICU admissions annually), pancreatic
      disorders of the newborn are rare. Congenital anomalies (such as annular
      pancreas) and endocrine disorders (such as hyperinsulinism of nesidioblastosis or
      hyperglycemia of neonatal diabetes mellitus) present many challenges to the
      personnel caring for these infants and their families. The potential mortality
      and morbidity of these disorders make it imperative for nurses and nurse
      practitioners working with infants to recognize and understand pancreatic
      dysfunction so that appropriate and timely intervention can prevent complications
      of brain injury and developmental delay. The home care needs of these infants and
      the extensive teaching needs of their parents require skilled nursing care to
      ensure a safe discharge.

PMID- 11949099
TI  - Nurses' experiences working with families in an NICU during implementation of
      family-focused developmental care.
AB  - PURPOSE: To explore and describe nurses' experiences while working with parents
      and infants receiving family-focused developmental care (FFDC), to gain insight
      into the process of changing from a traditional model of care to FFDC. DESIGN:
      The qualitative design was based on Spradley's method. SAMPLE: Data were
      collected by interviewing ten nurses who worked in an NICU during a pilot study
      of FFDC. Transcripts were analyzed using Spradley's domain analysis. FINDINGS:
      Four themes describe aspects of the transition from traditional care to FFDC: (1)
      negative experiences of FFDC, (2) transitions central to partnering with parents,
      (3) positive experiences of parental participation, and (4) organizational
      transitions necessary for the move to a family-centered model of care.
      CONCLUSION: Learning to share responsibility with families will require change in
      the NICU culture as well as in nurses' role identity.

PMID- 11949100
TI  - A comparison of kangaroo mother care and conventional cuddling care.
AB  - PURPOSE: To compare kangaroo mother care (KMC) and conventional cuddling care
      (CCC) in premature and small-for-gestational-age infants. DESIGN AND SAMPLE:
      Thirty mother-infant dyads in two Australian neonatal nurseries were randomly
      assigned to the KMC group or the CCC group. Both groups of mothers cuddled their
      babies for a minimum of two hours a day, five days a week while in the study,
      with the KMC group having skin-to-skin contact while the CCC group had contact
      through normal clothing. MAIN OUTCOME VARIABLE: The main outcome variables were
      infant weight gain, temperature maintenance during KMC and CCC, and length of
      hospital stay. RESULTS: The results showed no difference between groups on the
      Parental Stress Scale (NICU) or the Parental Expectations Survey. Infants in both
      groups experienced equivalent maintenance of or rise in temperature while out of
      the incubators, equal weight gain, equal length of stay in the hospital, and
      equal duration of breastfeeding.

PMID- 11949101
TI  - Chest x-ray findings in retained lung fluid.

PMID- 11949102
TI  - Meconium aspiration syndrome.

PMID- 11949103
TI  - Neonatal pneumonia.

PMID- 11949104
TI  - Pneumothorax in the newborn.
AB  - Air leak syndromes, and pneumothorax in particular, occur in the NICU. Careful
      nursing assessment, monitoring, and management strategies offer the infant with
      pneumothorax a good outcome.

PMID- 11949105
TI  - Case presentation: pneumothorax in the newborn.

PMID- 11949106
TI  - Gentamicin dosing recommendations.

PMID- 11949107
TI  - Thoughts on nurse shortages.

PMID- 11949108
TI  - End-of-life series, Part 2. Advance directives: improving end-of-life decision
      making.

PMID- 11949109
TI  - Correlates of anxiety, hostility, depression, and psychosocial adjustment in
      parents of NICU infants.
AB  - PURPOSE: The birth of a premature or critically ill infant can result in
      debilitating parental responses. This study identifies correlates of parental
      anxiety, hostility, depression, and psychosocial adjustment so that nurses can
      identify parents likely to need special attention or intervention. DESIGN: An
      explanatory, correlational design was used. SAMPLE: The study involved 469
      parents (mothers = 299, 65 percent; mean age 29.1 +/- 6.8 years) of infants
      hospitalized in five Level III NICUs. MAIN OUTCOME VARIABLE: The main outcomes
      were those variables which correlated with the independent variables and
      included: parent status (mother or father), ethnicity, employment status, and
      education. RESULTS: Parents experienced high levels of anxiety, hostility, and
      depression. Poorer family functioning, lower levels of social support, and lower
      perceived control were associated with higher levels of anxiety, hostility, and
      depression and with poorer adjustment. Parental status (mother or father),
      ethnicity, employment status, and education were significantly related to
      parental responses.

PMID- 11949110
TI  - Evaluation of cardiac size on the neonatal chest x-ray.

PMID- 11949111
TI  - Neonates with congenital heart disease: an overview.
AB  - The chest x-ray can be a valuable tool as part of the initial evaluation of a
      neonate with clinical signs of congenital heart disease. The radiographic
      appearance of pulmonary vascularity, as well as cardiac size and configuration,
      can provide information about the pathophysiologic effect of a cardiac lesion.
      Along with clinical evaluation of the infant, information gathered from the x-ray
      may be helpful in indicating which cardiac defect is involved. However, final
      identification of a defect would require further evaluation by echocardiogram or
      cardiac catheterization.

PMID- 11949112
TI  - Neonates with 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.

PMID- 11949113
TI  - Neonates with congenital cardiac defects with decreased pulmonary blood flow.
AB  - Lesions that cause decreased pulmonary blood flow are those that obstruct the
      RVOT. In general, the radiographic presentation includes the following: (1) Thin,
      poorly visualized pulmonary blood vessels with little extension beyond the
      perihilar region; (2) Dark, hyperlucent lung fields; and (3) Moderate to severe
      cardiomegaly, depending on the cardiac defect(s) present.

PMID- 11949114
TI  - Volunteerism and the neonatal nurse: a natural combination.

PMID- 11949115
TI  - Neonatal circumcision and pain management.

PMID- 11949116
TI  - Parasitic conjoined twins: a case report.
AB  - Parasitic twins are a rare phenomenon and a challenge for caregivers. Occurring
      as a result of abnormal processes in the first several weeks of embryologic
      development, this condition is oftentimes diagnosed by prenatal ultrasound. This
      unusual condition may go undiagnosed until the time of delivery, however, despite
      the availability and use of advanced ultrasound techniques. The challenges
      presented by this condition are multiple and complex. The following case report
      demonstrates some of these challenges.

PMID- 11949117
TI  - Apnea of prematurity: diagnosis, implications for care, and pharmacologic
      management.
AB  - Apnea is a disorder of respiratory control commonly seen in premature infants.
      Several mechanisms have been proposed to explain apnea, and many clinical
      conditions have been associated with its development. Apnea of prematurity is
      seen in infants less than 37 weeks gestation, with the incidence increasing as
      gestational age decreases. Expert and consistent nursing care is essential for
      management of premature infants with apnea. This article reviews the differential
      diagnosis, pathogenesis, and implications for care of apnea of prematurity.

PMID- 11949118
TI  - Effects of family coping and resources on family adjustment and parental stress
      in the acute phase of the NICU experience.
AB  - PURPOSE: To determine the relationship between family coping and resources and
      family adjustment and parental stress in the acute phase of the NICU experience.
      DESIGN: Correlational study based on the Resiliency Model of Family Stress,
      Adjustment, and Adaptation. Main study instruments included the State Anxiety
      scale of the State-Trait Anxiety Inventory, the Family Inventory of Resources for
      Management, the Family Crisis Oriented Personal Evaluation Scales, and the
      General Functioning subscale of the McMaster Family Assessment Device. SAMPLE:
      Data collected from 124 mother and father pairs within two to four days of their
      infant's admission to the NICU. MAIN OUTCOME VARIABLES: Family adjustment and
      parental stress. RESULTS: Adequate resources were more strongly related to
      positive adjustment and decreased stress than were either coping or being a first
      time parent. The relationships among the variables were generally the same for
      both parents. Mothers utilized more coping strategies than did fathers. PRACTICE
      RECOMMENDATIONS: Families with limited resources should be identified early to
      facilitate their adjustment to the NICU.

PMID- 11949119
TI  - The stomach.

PMID- 11949120
TI  - The small bowel.

PMID- 11949122
TI  - Pharmaceutical excipients.

PMID- 11949121
TI  - The colon and rectum.

PMID- 11949123
TI  - The hypothalamus.
AB  - The hypothalamus is an integral part of the neuroendocrine system. The anatomy,
      embryologic development, and normal function of the hypothalamus are described
      here. Pathophysiology of congenital abnormalities and brain injury is discussed
      and a case study examined. In addition, nursing implications of caring for such
      an infant are addressed.

PMID- 11949124
TI  - [Psychiatric sectorization in question].

PMID- 11949125
TI  - [Generous states in psychology].

PMID- 11949127
TI  - [The internet and psychoanalysis].

PMID- 11949126
TI  - [Feet in the water for a medico-psychological cellule].

PMID- 11949128
TI  - [Tobacco addiction, an orphan disease?].

PMID- 11949130
TI  - [Tobacco addiction and relationship dynamics in psychiatry].

PMID- 11949129
TI  - [Epidemiology and physiopathology of tobacco addiction].

PMID- 11949131
TI  - [Where can one legislate no-smoking rules?].

PMID- 11949132
TI  - [Therapeutic isolation and cigarette moment].

PMID- 11949133
TI  - [Dependence, is nicotine solely responsible?].

PMID- 11949134
TI  - [The nurse in relation to institutional dynamics].

PMID- 11949135
TI  - [Daily coping, a nursing goal for rehabilitation of schizophrenic patients].

PMID- 11949137
TI  - [The Court of Accounts praises a global remodeling of the politics of mental
      health].

PMID- 11949136
TI  - [White frocks and black coffee].

PMID- 11949138
TI  - ["Informing consumers of mental health, what is the change?"].

PMID- 11949140
TI  - Student nurses' experience of interaction with culturally diverse psychiatric
      patients.
AB  - A study of Baccalaureate nursing students was conducted to explore and describe
      undergraduate nursing students' experience of interaction with culturally diverse
      psychiatric patients. Thirty-seven nursing students participated in this research
      project. Sixteen of the students came from a predominantly black university and
      the other twenty-one students came from a predominantly white university. Both
      universities are situated in the same city and allocate their nursing students to
      the same psychiatric hospital for practical experience. The student nurses
      reported having experienced both positive and negative aspects of interacting
      with culturally diverse psychiatric patients. Positive aspects included inter
      alia, optimism, racial unity, equality of facilities, enrichment and challenge,
      whereas negative experience included inter alia, discrimination, superiority
      complex, cultural ignorance, ineffectiveness of patient care, hostility and
      general unhappiness. The undergraduate program should therefore begin to include
      cultural content in the curriculum so as to enable future nurse practitioners to
      utilize a culture-sensitive approach in rendering care to their patients.

PMID- 11949139
TI  - Community-based curriculum in psychiatric nursing science.
AB  - As community-based health care delivery is now a prominent feature of the health
      care system in South Africa, nursing curricula are being challenged to prepare
      student nurses for community-based nursing roles and responsibilities. The
      purpose of this study was to describe guidelines for a community-based curriculum
      in psychiatric nursing science for a nursing college in KwaZulu-Natal. A
      qualitative, quantitative, exploratory, descriptive and contextual design was
      employed. To reach the purpose of the study, a situational analysis was done in
      three phases to identify the principles for a community-based curriculum for
      psychiatric nursing science. PHASE I: A document analysis of relevant government
      policies and legislation. PHASE II: Statistics from psychiatric hospitals and
      community psychiatric clinics. PHASE III: Focus group interviews with nurse
      educators and literature control and conceptual framework. The principles
      obtained from the three phases were used to formulate the guidelines for a
      community-based curriculum in psychiatric nursing science. (PHASE IV): Eight
      guidelines with practical implications are described for the implementation of a
      Community-based curriculum in Psychiatric Nursing Science.

PMID- 11949141
TI  - Clinical accompaniment: the critical care nursing students' experiences in a
      private hospital.
AB  - The quality of clinical accompaniment of the student enrolled for the post-basic
      diploma in Medical and Surgical Nursing Science: Critical Care Nursing (General)
      is an important dimension of the educational/learning programme. The clinical
      accompanist/mentor is responsible for ensuring the student's compliance with the
      clinical outcomes of the programme in accordance with the requirements laid down
      by the Nursing Education Institution and the South African Nursing Council. The
      purpose of this study was to explore and describe the experiences of the students
      enrolled for a post-basic diploma in Medical and Surgical Nursing Science:
      Critical Care Nursing (General), in relation to the clinical accompaniment in a
      private hospital in Gauteng. An exploratory, descriptive and phenomenological
      research design was utilised and individual interviews were conducted with the
      ten students in the research hospital. A content analysis was conducted and the
      results revealed both positive and negative experiences by the students in the
      internal and external worlds. The recommendations include the formulation of
      standards for clinical accompaniment of students, the evaluation of the quality
      of clinical accompaniment of students and empowerment of the organisation,
      clinical accompanists/mentors and clinicians.

PMID- 11949142
TI  - Problems experienced by role players within the managed healthcare context in
      Gauteng.
AB  - Role players within the context of managed healthcare in Gauteng experience
      problems in the delivery of healthcare, which negatively affect their working
      relationships. This is turn, affects the quality of care provided to patients.
      The purpose of this study is to explore and describe the problem experienced by
      different role players within the context of managed healthcare in Gauteng, as
      well as the suggested solutions to counteract these problems. These results will
      be utilised as the basis of a conceptual framework to formulate a strategy to
      enhance the working relationships amongst these role players. The strategy will
      not be discussed in this article as the focus is on the problems experienced by
      the role players in the delivery of healthcare, as well as suggested solutions in
      the counteraction thereof. A qualitative, exploratory, descriptive and contextual
      study was followed to explore and describe the problems, as well as the suggested
      solutions to counteract these problems. Focus group interviews were conducted to
      collect data from three private hospitals, three managed care organisations and
      four general medical practitioners in Gauteng. The participants were purposively
      and conveniently selected. Content analysis as described by Tesch (1990) was
      followed to analyse the data. The main problems experienced were related to
      inadequate communication, inadequate staff competence, cost saving versus quality
      care, procedural complexity, perceived loss of power by doctors and patients and
      the system of accounts payment. The suggested solutions focused mainly on
      empowerment and standardisation of procedures. It is recommended that replication
      studies of this nature be conducted in other provinces and that ethical standards
      are formulated within the managed healthcare context.

PMID- 11949143
TI  - The implementation of the Choice on Termination of Pregnancy Act: some empirical
      findings.
AB  - The Choice on Termination of Pregnancy Act of 1996 substantially liberalised
      abortion law. Whilst a substantial number of terminations of pregnancies (TOPs)
      have already been performed in terms of the new Act, it has also surfaced that an
      array of factors of various kinds may impede its further implementation and
      operation. A study was undertaken to determine the nature and extent of any such
      impediments to the implementation of the Choice on Termination of Pregnancy Act.
      More specifically a survey was conducted amongst a sample of 75 women who had
      undergone a TOP since the implementation of the Act; health professionals and
      social workers who provide TOP services (n = 16); and health professionals and
      social workers who are in a position to refer women to TOP facilities (n = 63).
      Overall, the clients were well treated at the TOP facilities, and were satisfied
      with the service given to them. However, post-counselling and to a lesser extent
      pre-counselling, is lacking. Counselling is important as a considerable
      proportion of the clients suffered from emotional feelings usually associated
      with depression and/or self-reproach before and after the termination procedure.
      Furthermore these clients did not usually discuss their termination with family
      members. TOP service providers were dissatisfied with the TOP facilities,
      especially the insufficient number of consultation and counselling rooms. Health
      care workers in a position to refer clients to TOP facilities were not always
      willing to do so, thereby obstructing the referral system. In the main, it is
      recommended that the entire TOP procedure should be done at clinics/hospitals so
      that clients will not have to do inductions at home, more trained staff should be
      available, facilities should be adequate and accessible, and there should be
      psychological support for staff.

PMID- 11949145
TI  - The experiences and perceptions of nursing service managers regarding
      transformation of health services in selected provincial academic health
      complexes.
AB  - Nursing service managers are challenged with enormous transformations within the
      new political dispensation in South Africa. The objective of the study was to
      explore and describe the experiences and perceptions of the nursing service
      managers regarding transformation of health services in selected Provincial
      Academic Health Complexes. A qualitative, exploratory, descriptive and
      phenomenological design was employed utilising focus group interviews and
      narratives as methods of data collection. After content analysis was performed,
      results were grouped into management of health service transformation and quality
      of patient care in relation to the levels of the organisation. The levels in the
      organisation are individual level, group level, departmental level and
      organisational level. Positive and negative experiences and perceptions were
      identified.

PMID- 11949144
TI  - [The function of the community nurse in acute care district health services].
AB  - In South Africa patients are discharged sooner from hospitals, because of a
      shortage in hospital beds, thus more patients are nursed at home. More prominence
      should be given to the function of the community nurse in these mainly curative
      health services. An explorative and descriptive study was performed in order to
      explore and describe the functions of the community nurse in the context of the
      district health service in South Africa. These functions described in this
      article were determined by means of an analysis of duty sheets as well as the use
      of questionnaires which was based on a literature study. Some conclusions and
      recommendations were made on which the community nurse can base these nursing
      services.

PMID- 11949146
TI  - Perceptions of nurse educators about problem-based learning.

PMID- 11949147
TI  - The quality of nursing service management in South African hospitals.
AB  - The purpose of this study is to determine--explore and describe--the quality of
      nursing service management in South African hospitals. A combined qualitative and
      quantitative pre- and post-test research strategy, in accordance with the COHSASA
      programme, was utilised. The hospitals implement the national standards during
      the preparatory phase, after having entered into an agreement with COHSASA. They
      determine their baseline status by means of an assisted self-evaluation. This is
      followed by an external survey phase where the hospital's compliance with the
      standards is evaluated. The nursing service is one of the professional services
      included in the accreditation programme. Their performance is compared with
      selected other professional services and their compliance with the core elements
      is also evaluated. The nursing services in South Africa are compliant with the
      national standards. The deficiencies are mainly within the quality improvement
      programmes that require further development and refinement.

PMID- 11949148
TI  - Recognition of prior learning: its relevance to the proposed unified model of
      education and training for South African nurses.
AB  - Recognition of Prior Learning (R P L) is a fairly new concept in South Africa,
      and hence different people have different views about R P L. Through this paper,
      an attempt is made to shed some light on the historical background as well as the
      philosophical and theoretical underpinnings of R P L. It is hoped that this
      information will help those nurse educators wishing to experiment with R P L to
      have a better understanding of how the concept came about. The relevance of R P L
      to the Unified model of nurse training proposed by the South African Nursing
      Council is also discussed.

PMID- 11949149
TI  - Accessibility of adolescent health services.
AB  - Adolescents represent a large proportion of the population. As they mature and
      become sexually active, they face more serious health risks. Most face these
      risks with too little factual information, too little guidance about sexual
      responsibility and multiple barriers to accessing health care. A typical
      descriptive and explanatory design was used to determine what the characteristics
      of an accessible adolescent health service should be. Important results and
      conclusions that were reached indicate that the adolescent want a medical doctor
      and a registered nurse to be part of the health team treating them and they want
      to be served in the language of their choice. Family planning, treatment of
      sexually transmitted diseases and psychiatric services for the prevention of
      suicide are services that should be included in an adolescent accessible health
      service. The provision of health education concerning sexual transmitted diseases
      and AIDS is a necessity. The service should be available thought out the week
      (included Saturdays) and within easy reach. It is recommended that minor changes
      in existing services be made, that will contribute towards making a health
      delivery service an adolescent accessible service. An adolescent accessible
      health service can in turn make a real contribution to the community's efforts to
      improve the health of its adolescents and can prove to be a rewarding
      professional experience to the health worker.

PMID- 11949150
TI  - Profile of care given to patients with blunt chest injuries within the first 48
      hours.
AB  - This study was conducted in the trauma unit of a large academic hospital in
      Johannesburg, South Africa. The study aimed at describing the nature of care that
      patients with blunt chest injuries received during the first 48 hours after
      injury. A descriptive survey was chosen using retrospective and prospective
      record review to obtain data. The sample comprised 60 records of patients who
      were admitted to the hospital due to blunt chest injuries between January 1997
      and June 1998. Descriptive statistics were used to present and analyse data. The
      study showed that: (i) Blunt chest trauma victims received a thorough initial
      assessment and care. No missed injuries were identified on subsequent assessment;
      (ii) More than half of the patients spent over one hour in the accident/emergency
      department before admission to the trauma ward or intensive care unit (ICU);
      (iii) Motor vehicle accidents (MVA) were the commonest cause of injury while
      pedestrian vehicle accidents (PVA) were often fatal; (iv) Nurses are good
      providers of care but poor in prescribing and documenting care; (v) Pain
      assessment and psychosocial care was often neglected; (vi) Less than half the
      patients developed complications during the first 48 hours; pain and pneumonia
      being the most common complications encountered.

PMID- 11949151
TI  - The community health clinics as a learning context for student nurses.
AB  - The purpose of the research study was to describe guidelines to improve the
      community health clinics as a learning context conductive to learning. The
      objectives of the study commenced by getting the perception of student nurses
      from a nursing college in Gauteng; community sisters from ten community health
      clinics in the Southern Metropolitan Local Council and college tutors from a
      college in Gauteng. The research design and method used, consisting of a
      qualitative, exploratory, descriptive and contextual approach and the design was
      divided into two phases. Phase one consisted of a field/empirical study and phase
      two of conceptualization. In all the samples follow-up focus group interviews
      were conducted to confirm the findings. To ensure trustworthiness, Lincoln and
      Guba's model (1985) was implemented and data analysis was according to Tesch's
      model (1990 in Creswell 1994:155) based on a qualitative approach. The conceptual
      framework discussed, indicating a body of knowledge, was based on the study and
      empirical findings from phase one to give clear meaning and understanding
      regarding the research study.

PMID- 11949152
TI  - Online teaching and learning in a graduate course in nursing education.
AB  - Information technology has a potential to be the answer to one of Africa's most
      pressing problems-providing education to a number of geographically dispersed
      learners, who currently have to leave their countries for a number of years in
      order to pursue their studies elsewhere. The School of Nursing at the University
      of Natal launched an online graduate course in nursing education at the beginning
      of the year 2000 for the first time as part of a masters degree programme. A
      number of lessons have been learned from this experience. Firstly, it took too
      long to arrive at 'closure' on discussion of any one particular theme. There
      seemed to be a perpetual feeling of never "completing" teaching/learning tasks.
      Ordinarily, in a face-to-face (f2f) classroom, a particular theme or topic is
      scheduled for a particular lecture period. More often than not, whether clarity
      and/or resolution has been attained, the discussion moves on to the next theme,
      or topic. This has not been easy to do in computer mediated communication (CMC).
      The students' contributions, however, seemed more thought out and more focused
      than had been the case in the f2f classes. Secondly, the essentiality/importance
      of structure became apparent very early. After an initial tentative and slow
      start, once the students felt comfortable with the computer "classroom", the
      bulletin board was flooded with messages, necessitating re-thinking the original
      structure.

PMID- 11949153
TI  - Critical thinking by nurses on ethical issues like the termination of
      pregnancies.
AB  - This research forms part of a larger interdisciplinary research project on the
      termination of pregnancies. The focus of this part of the project is on the
      ethical issues related to termination of pregnancies. The practice of the
      professional nurse is confronted with ethical dilemmas and disputes. Whether the
      nurse chooses to participate in the termination of pregnancies or not, the core
      function of the nurse is that of counseling and ethical decision-making.
      Effective counseling requires empathy, respect for human rights and unconditional
      acceptance of a person. Making ethical decisions implies making critical
      decisions. It is self-evident, therefore, that such decisions should be based on
      sound arguments and logical reasoning. It is of vital importance that ethical
      decisions can be justified on rational ground. Decision-making is a critical
      thinking approach process for choosing the best action to meet a desired goal.
      The research question that is relevant for this paper is: Are nurses thinking
      critically about ethical issues like the termination of pregnancies? To answer
      the research question a qualitative, exploratory, descriptive design was used
      (Mouton, 1996:103-169). Registered nurses were selected purposively (Creswell,
      1994:15). 1200 registered nurses completed the open-ended questionnaires. Focus
      group interviews were conducted with 22 registered nurses from a public hospital
      for women and child health services. Data analysis, using secondary data from
      open-ended questionnaires and transcribed focus group interviews, were based on
      the approach of Morse and Field (1994:25-34) and Strauss and Corbin (1990). The
      themes and categories from open coding were compared, conceptualized and linked
      with theories on critical thinking (Paul, 1994; Watson & Glaser, 1991 and the
      American Philosophical Association, 1990). The measures of Lincoln and Guba
      (1985) and Morse (1994) related to secondary data analysis were employed to
      ensure trustworthiness. Based on these findings the researcher concluded that
      nurses are not thinking critically when making ethical decisions concerning the
      termination of pregnancies. Recommendations are made as a possible solution for
      this problem.

PMID- 11949154
TI  - [The experience of the patient and the registered nurse during tuberculosis
      education].
AB  - This article focused on the problem that patients suffering from tuberculosis
      often stop taking their prescribed medicine and become defaulters. Although
      various factors could possibly contribute to the non compliance of the patients,
      this research had focused only on the teaching-learning situation. The experience
      of both the primary health nurse and the patient suffering from tuberculosis,
      during the teaching-learning situation in tuberculosis education, has been
      explored and described within the context of the North West Province.
      Phenomenological interviews were conducted with primary health nurses and
      defaulting patients suffering from tuberculosis. Interviews were recorded on tape
      and transcribed verbatim. The method of content analysis was used. The research
      has proven that adult-teaching principles have not been established in the
      teaching-learning situation and that the parent-child ego state predominates in
      communication.

PMID- 11949155
TI  - Traditional healers and cancer prevention.
AB  - The increase in the incidence of cancer in South Africa necessitates the
      expansion of preventative efforts. This study shows that traditional healers in
      Atteridgeville are consulted by a range of people in their communities, have a
      basic knowledge of cancer, provide health education to their patients and are
      willing to participate in cancer preventative strategies. They are therefore
      ideally suited to augment the services of westernized health care workers. The
      issue of professionalization is explored and a procedure is suggested whereby the
      training of traditional healers can be enhanced so as to facilitate their
      professionalization and their collaboration with other health care workers in the
      prevention of cancer.

PMID- 11949157
TI  - [Axillary temperature compared to tympanic membrane temperature in children].
AB  - The purpose of the study was to measure the axillary temperature at three, six
      and nine minutes in a hundred children between the ages of one and twelve years
      who were selected in a non-random deliberate way, and to compare the measurements
      with the tympanic membrane temperature (golden standard) which was measured in
      the test persons at the same time. The results were described by sensitivity,
      specificity, limits of agreement, and predictive values. From some of the
      findings of the research it is apparent that the axillary temperature reading
      increased after measurement of three, six and nine minutes. A maximum temperature
      reading was reached after three minutes in only 9% of the test persons, in 25%
      after six minutes and in 66% after nine minutes. From the findings it is clear
      that the ranges that were used influenced the sensitivity of the measurements,
      and it would appear that the range 35.5 degrees C to 37.2 degrees C was the best
      range to measure pyrexia in the age group one to 12 years. The 9-minute
      measurement then had the highest sensitivity. However, the specificity of
      measurement in this range was lower. The conclusion was drawn that axillary
      temperature measurement is an acceptable method, with certain reservations, to
      use as screening method for pyrexia in emergency divisions or clinics.

PMID- 11949156
TI  - Adolescent mothers' utilisation of reproductive health services in the Gauteng
      Province of the Republic of South Africa.
AB  - A financial grant was received from the World Health Organization (WHO) during
      1998 to establish whether adolescent mothers (aged 19 or younger at the birth of
      their babies) utilized contraceptive, emergency contraceptive and termination of
      pregnancy (TOP) services in the Republic of South Africa (RSA). This report
      refers to data obtained from 111 questionnaires completed by dolescent mothers
      between January 2000 and May 2000 in the Gauteng Province; 61 in the Pretoria and
      50 in the Garankuwa areas, and excluding the 12 completed questionnaires used for
      pretesting the research instrument. The biographic data of the 111 adolescent
      mothers indicated that the minority were married, employed or earned sufficient
      income to care for themselves and their babies. However, the minority used
      contraceptives prior to conception, none used emergency contraceptives or
      termination of pregnancy (TOP) services. The minority attended ante-natal clinics
      five or more times during their pregnancies, and a negligible number indicated
      that they had ever been treated for sexually transmitted diseases (STDs). These
      findings indicate that the 111 adolescent mothers in Gauteng who participated in
      this survey did not make optimum use of the available reproductive health (RH)
      care services. Education about sex, pregnancy and contraceptives should commence
      at the age of 10, but no later than the age of 12 as the majority of respondents
      did not have the necessary knowledge to make informed decisions about their
      futures. The accessibility of contraceptive, emergency contraceptive and TOP
      services for adolescents should be investigated in specific areas and attempts
      made to enhance such accessibility. This might necessitate offering these
      services over weekends or during evenings when school girls could attend without
      fear of meeting their mothers, aunts or teachers at these clinics.

PMID- 11949158
TI  - The experience of mothers caring for their teenage daughters' young children.
AB  - The purpose of this study was firstly to explore and describe the experiences of
      mothers who are looking after their teenage daughters' young children. Secondly,
      to formulate guidelines (based on the results obtained) for psychiatric nurses in
      assisting these mothers to mobilise resources in order to promote, maintain and
      restore their mental health as an integral part of health. An exploratory,
      descriptive, contextual and qualitative design was used and Guba's model for
      ensuring trustworthiness in qualitative research was applied. The
      phenomenological approach was used to collect and analyse data from a sample of
      seven respondents who were purposively selected. Three independent themes emerged
      from the analysis of results: Meaning of the parenting role, life-style changes
      and support systems. The results further show that for these mothers the problem
      of teenage pregnancy and parenthood ends up being their problem. Their
      experiences in looking after these babies, although sometimes fulfilling and
      meaningful, are most of the time stressful. This has implications on their mental
      health. Guidelines are recommended in order to facilitate these mothers to
      mobilise their resources for mental health.

PMID- 11949159
TI  - Meanings and expressions of care and caring for elders in urban Namibian
      families: a transcultural nursing study.
AB  - Since Namibia's Independence in 1990, the population of elders--persons 65 years
      old and older--in urban communities is growing steadily. As such, requests for
      home health care, health counselling, respite care and residential care for aging
      members of society are overwhelming nurses and the health care system. This study
      expands transcultural nursing knowledge by increasing understanding of generic
      (home-based) patterns of elder care that are practised and lived by urban
      Namibian families. Guided by Madeleine Leininger's theory of culture care
      diversity and universality and the ethnonursing research method, emic (insider)
      meanings and expressions of care and caring for elders in selected urban
      households have been transposed into five substantive themes. The themes, which
      depict what carring for elders means to urban families, include: 1 nurturing the
      health of the family, 2 trusting in the benevolence of life as lived, 3 honouring
      one's elders, 4 sustaining security and purpose for life amid uncertainty, and 5
      living with rapidly changing cultural and social structures. These findings add a
      voice from the developing world to the evolving body of transcultural nursing
      knowledge. Synthesis of findings with professional care practices facilitates the
      creation of community-focussed models for provisioning culturally congruent
      nursing care to elders and their families in urban Namibia.

PMID- 11949160
TI  - What is it that matters most in the practice of nursing children?
AB  - This article discusses the results of a workshop designed as an action research
      cycle to ascertain what matters most in the practice of nursing children in South
      Africa today. The workshop was convened at the University of Cape Town (UCT), in
      order to guide and direct the newly established post-basic, children's nursing
      pathway in the Bachelor of Nursing for Registered nurses [BN(RN)] programme. The
      participants were eight experienced paediatric nurses, currently practising in a
      variety of settings in the Western Cape. The results show that the participants
      move from their original task- and procedure-based perspective to a more
      processive one in which the focus of the learning is relational, emphasising the
      family and culture of the child.

PMID- 11949161
TI  - Adapting to and implementing a problem- and community-based approach to nursing
      education.
AB  - The process of change, implemented by the School of Nursing at the University of
      the Orange Free State so that a paradigm shift in approaches to nursing education
      at undergraduate level could be achieved, is outlined. The necessity to change,
      the identification of external and internal variables that impact on change, the
      founding of a support system, the process of overcoming resistance to change, the
      evaluation of the process of change and options for the future, are discussed.
      The rationale for the implementation of a problem-based teaching strategy and the
      phasing in of a community-based approach to teaching as the heart of the process
      of change are discussed.

PMID- 11949163
TI  - The Chicago Tribune series on nursing mistakes.

PMID- 11949162
TI  - [Effective communication with the mentally challenged person during treatment of
      minor ailments].
AB  - The research objectives were to explore and describe the nature of communication
      with the mentally retarded adult during treatment of minor ailments; and to
      describe guidelines for the community nurse in order to facilitate more effective
      communication during the treatment of minor ailments in the mentally retarded
      adult for the promotion, maintenance and restoration of the mentally retarded
      individual's health. The community nurse pays attention to the protection of the
      mentally retarded individual's health, and identifies and treats minor ailments
      encountered by the mentally retarded individual. Because of the disability of the
      adults, lacking communication and obstacles in the exchange and interpretation of
      communication, could take place between the community nurse and the mentally
      retarded adult. The responsibility lies with the community nurse to facilitate
      effective communication, since the mentally retarded individual is not always
      capable of speaking on his/her own behalf. Guidelines are needed for the
      facilitation of effective communication between the community nurse and the
      mentally retarded adult during the treatment of minor ailments. In this research,
      use were made of a qulitative, exploratory, descriptive and contextual design.
      The research method consisted of participative observation during which video
      recording and the taking of field notes were applied. Two themes were identified
      during data analysis, namely: Verbal communication is aimed at the treatment of
      wounds. The more functional and task-orientated the community nurse's interaction
      with the mentally retarded individual, the more the mentally retarded individual
      would generate symptoms to establish emotional contact and interaction; The non
      verbal behaviour of the community nurse focuses on the treatment of wounds and
      organisation of the environment. The more structure is created, the more play-out
      behaviour is shown by the mentally retarded individual in need of contact. The
      researcher came to the conclusion that the community nurse refrains form
      near/close contact with the mentally retarded individual, to bridge her own
      discomfort. The community nurse is "busy" with the act of treating wounds, in
      order to refrain from effective interaction.

PMID- 11949165
TI  - Mandatory overtime and on call: growing concerns for nurses.

PMID- 11949168
TI  - [Dermatology's desperate quest--association of nurses!].

PMID- 11949169
TI  - [Examination of otorhinolaryngologic cancers].

PMID- 11949167
TI  - 2000 update: foreign nurse recruitment.

PMID- 11949170
TI  - [Work stress, a great danger].

PMID- 11949172
TI  - [Pansement MediSet: repair for home wounds in complete privacy].

PMID- 11949171
TI  - ["THe nursing profession, a career for life?"].

PMID- 11949173
TI  - [Prevention of the risk of the diabetic foot].

PMID- 11949175
TI  - [How should one announce a diagnosis of cancer?].

PMID- 11949174
TI  - [Caregivers and those cared for in cancer].

PMID- 11949176
TI  - [Nursing consultation for optimal care of cancer patients].

PMID- 11949178
TI  - [Dialog about breast cancer].

PMID- 11949177
TI  - [Nursing consultation for patients participating in a clinical trial].

PMID- 11949179
TI  - [Over 500 oncologic nurses meet in Paris].

PMID- 11949180
TI  - [Perspectives for European nurses in oncology].

PMID- 11949181
TI  - [THe 21st century, towards which end of life?].

PMID- 11949182
TI  - [14th Conference of Nurses].

PMID- 11949183
TI  - Changing the guard.

PMID- 11949184
TI  - Parting shots. Interview by Colin Parish.

PMID- 11949185
TI  - Neutral territory.

PMID- 11949186
TI  - In small doses.

PMID- 11949187
TI  - She knew when to let me stumble.

PMID- 11949188
TI  - The effects of giving patients pre-operative information.
AB  - BACKGROUND: A literature review was undertaken to establish the effects on
      surgery patients' anxiety levels of giving them information before they attend
      theatre. CONCLUSION: There is plenty of evidence that pre-operative information
      giving can reduce patients' anxiety regarding surgery. It might be better to
      provide this information before patients are admitted to hospital, as they are
      more likely to be able to take in the information if they are not already feeling
      anxious. To provide better patient care, members of the peri-operative team
      should work together to prepare patients for the psychological and physical
      consequences of surgery.

PMID- 11949189
TI  - MRSA: risk assessment and flexible management.
AB  - MRSA is an increasing problem in hospitals, particularly among older patients.
      The author discusses prevention of cross-infection, with an emphasis on the
      importance of risk assessment and good infection control procedures, rather than
      the routine isolation of infected patients.

PMID- 11949190
TI  - Common cardiac arrhythmias.
AB  - The interpretation of cardiac arrhythmias plays an important role in the
      diagnosis of cardiac disorders. Helen Hand examines the physiology of the heart,
      the electrical conduction mechanism, cardiac rhythm disorders and cardiac
      monitoring.

PMID- 11949192
TI  - Breathing space.

PMID- 11949193
TI  - Health in household context: living arrangements and health in late middle age.
AB  - People living in some arrangements show better health than persons in other
      living arrangements. Recent prospective studies document higher mortality among
      persons living in particular types of households. We extend this research by
      examining the influence of household structure on health using longitudinal data.
      We theorize that individuals experience role-based household relations as sets of
      resources and demands. In certain household structures, individuals are more
      likely to perceive that the demands made on them outweigh the resources available
      to them. This perceived imbalance poses a risk to individual health. We test our
      expectations by analyzing the relationship between living arrangements and health
      using data from waves 1 and 2 of the Health and Retirement Study. We focus on
      persons ages 51-61 and explore gender differences. We find prospective links
      between household structure and self-rated health, mobility limitation, and
      depressive symptoms. Married couples living alone or with children only are the
      most advantaged; single women living with children appear disadvantaged on all
      health outcomes. Men and women in other household types are disadvantaged on some
      health outcomes. Our results suggest that the social context formed by the
      household may be important to the social etiology of health. In addition, they
      qualify the well-known link between marital status and health: The effect of
      marital status on health depends on household context.

PMID- 11949194
TI  - State expenditures on home and community based services and use of formal and
      informal personal assistance: a multilevel analysis.
AB  - Despite wide state variation in commitment to home and community-based services
      (HCBS) for functionally impaired older persons, little is known about how such
      variation affects older adults' strategies to compensate for their functional
      limitations. This study examines the association of state HCBS expenditures with
      use of formal and informal personal assistance among non-institutionalized older
      Americans aged 70 and older with functional limitations. We conducted multilevel
      multinomial logistic regression analysis using data from the first wave of the
      Assets and Health Dynamics among the Oldest Old Survey, combined with data on
      state HCBS expenditures. Controlling for individuals' demographic, socioeconomic,
      and care needs factors, persons residing in states with higher HCBS expenditures
      were more likely to use formal personal assistance, but not less likely to use
      informal assistance. Our study suggests state variation in HCBS expenditures
      leads to inequitable access to formal personal assistance, especially among those
      with high functional limitations.

PMID- 11949195
TI  - Causal connections between socio-economic status and health: reciprocal effects
      and mediating mechanisms.
AB  - Using structural equation modeling techniques on data from a nationally
      representative longitudinal survey, we first explored the reciprocal
      relationships between socio-economic status (SES) and health status. We then
      estimated the degree to which health-related lifestyles/behaviors and
      psychosocial distress are mediating mechanisms of these relationships. As
      predicted, SES positively affects health, and health positively affects SES.
      Although the causal path from SES to health is stronger than the reverse, these
      findings confirmed the hypothesis that both social causation and health selection
      contribute to social inequalities in health. In terms of the mediating mechanisms
      through which SES and health affect each other, more than a third of the overall
      SES-health relationship was accounted for by health-related lifestyles/behaviors
      and psychosocial distress. A notable part of the effect of SES on health is due
      to differences in psychological distress, with the effects of health-related
      lifestyles/behaviors being much smaller. On the other hand, in terms of the
      effects of health on SES, differences in weight and sleeping behavior are more
      important than psychological distress.

PMID- 11949196
TI  - Health lifestyles in Russia and the socialist heritage.
AB  - This study examines the relationship between socialist ideology and the current
      negative health lifestyles of the Russian population. We explore the possibility
      that Soviet-style socialism with its negation of individuality and individual
      initiative in health matters promoted the development of a passive orientation
      toward healthy living. Using a national sample, we compare the health practices
      of those Russians who wish to return to socialism as it was before Gorbachev to
      those of Russians who favor staying with the present political and economic
      course or adopting other reforms. If a socialist ideology has indeed fostered a
      lack of responsibility for individual health promotion in Russia today, those
      persons wishing to return to socialism would be less likely to adopt a positive
      health lifestyle. Our data show that this is indeed the case, as pro-socialist
      respondents demonstrate less activity toward achieving health than antisocialists
      -although neither group collectively practices a healthy way of life.

PMID- 11949197
TI  - The influence of parental separation on smoking initiation in adolescents.
AB  - Most adult smokers start smoking when they are adolescents and, the prevalence of
      smoking declines less than other unhealthy behaviors as people mature.
      Understanding why adolescents start smoking is, therefore, key to developing
      effective policy aimed at lowering the prevalence of smoking in both children and
      adults. In this study, I suggest that parental separation is one possible risk
      factor for smoking initiation. I use a nationally representative sample of
      American adolescents interviewed at two points in time to examine the influence
      of parental separation on smoking initiation. Two questions are addressed. First,
      is there a relationship between parental separation and the likelihood that an
      adolescent will initiate smoking? Second, if there is a relationship, through
      what factors does parental separation operate to influence the initiation of
      smoking in adolescents? My findings suggest that parental separation increases
      the likelihood that adolescents will start smoking. It does so in part by raising
      depressive symptoms and rebelliousness in adolescents. Despite the significance
      of these indirect effects, however, the bulk of the effect of parental separation
      on smoking initiation is direct.

PMID- 11949198
TI  - Thriving and surviving in a new medical career: the case of hospitalist
      physicians.
AB  - Managed care is cultivating a variety of new work careers within the medical
      profession, and it is worth asking whether they will function as long- or shorter
      term career options for the individuals who participate in them. This paper uses
      the specific case of hospitalist physicians to explore how the surrounding social
      and economic work contexts contribute to two individual-level outcomes that
      inform the issue of career longevity: the concepts of burnout and intent to stay
      in the career. The findings of a national survey of hospitalists reveal that job
      burnout and intent to remain in the career are more meaningfully associated with
      favorable social relations involving colleagues, co-workers, and patients than
      with negative experiences related to the economically induced pressures of the
      job, such as reduced autonomy and the use of financial incentives. In addition,
      career longevity is enhanced by the extent to which individual physicians pursue
      intrinsic and extrinsic rewards through their choices to become hospitalists.
      These findings demonstrate that sociologists should pay greater attention to the
      career trajectories of contemporary doctors in order to understand larger scale
      professional stratification within medicine. They also offer empirical support
      for redirecting our focus towards the relational dynamics that shape these
      trajectories.

PMID- 11949199
TI  - The unexpected influence of physician attributes on clinical decisions: results
      of an experiment.
AB  - This experiment was designed to determine: (1) whether patient attributes
      (specifically a patient's age, gender, race, and socioeconomic status)
      independently influence clinical decision-making; and (2) whether physician
      characteristics alone (such as their gender, age, race, and medical specialty),
      or in combination with patient attributes, influence medical decision-making.
      METHODS: An experiment was conducted in which 16 (= 2(4)) videotapes portraying
      patient-physician encounters for two medical conditions (polymyalgia rheumatica
      (PMR) and depression) were randomly assigned to physicians for viewing. Each
      video presented a combination of four patient attributes (65 years or 80 years of
      age; male or female; black or white; blue or white collar occupation). Steps were
      taken to enhance external validity. One hundred twenty-eight eligible physicians
      were sampled from the northeastern United States, with numbers balanced across 16
      (= 2(4)) strata generated from the following characteristics (male or female; <
      15 or > or = 15 years since graduation; black or white; internists or family
      practitioners). The outcomes studied were: 1) the most likely diagnosis; 2) level
      of certainty adhering to that diagnosis; and 3) the number of tests that would be
      ordered. RESULTS: Patient attributes (namely age, race, gender, and socioeconomic
      status) had no influence on the three outcomes studied (the most likely
      diagnosis, the level of certainty, and test ordering behavior). This was
      consistent across the two medical conditions portrayed (PMR and depression). In
      contrast, characteristics of physicians (namely their medical specialty, race,
      and age) interactively influenced medical decision-making. CONCLUSION:
      Epidemiologically important patient attributes (which Bayesian decision theorists
      hold should be influential) had no effect on medical decision-making for the two
      conditions, while clinically extraneous physician characteristics (which should
      not be influential) had a statistically significant effect. The validity of
      idealized theoretical approaches to medical decision making and the usefulness of
      further observational approaches are discussed.

PMID- 11949200
TI  - The golden age of medicine in Damascus.

PMID- 11949201
TI  - Haemodynamic and EKG changes in patients undergoing minimally invasive direct
      coronary artery bypass.
AB  - BACKGROUND AND OBJECTIVES: The objective of the report is to monitor, in patients
      undergoing minimally invasive direct coronary artery bypass surgery (MIDCAB), the
      haemodynamic parameters, ST segment changes and the incidence of arrhythmias
      during clamping of the coronary artery and following reperfusion. METHODS: Twelve
      patients scheduled for elective MIDCAB surgery during isoflurane anesthesia were
      enrolled in the study. Patients were monitored by a pulmonary artery
      thermodilution catheter, an arterial line and 5 leads ECG. The different
      haemodynamic parameters, the ST segment changes, as well as the occurrence of
      arrhythmias during coronary clamping and ten minutes following reperfusion were
      compared to the control values. RESULTS: No significant changes in the cardiac
      index followed clamping of the coronary artery. However, the ST segment was
      significantly elevated. Following coronary reperfusion, the ST segment recovered
      to the baseline values, and the cardiac index significantly increased more than
      the baseline value (3.5 +/- 1.1 l/min/m2 vs 2.6 +/- 0.7 l/min/m2). However,
      reperfusion was associated with multiple ventricular extrasystoles in four
      patients. The elevation of the ST segments during coronary clamping was higher in
      the four patients who developed reperfusion arrhythmias (0.9 +/- 0.4 mm); one of
      the patients had preoperative frequent VPBs, two patients had history of unstable
      angina, while the fourth patient had 70% proximal stenosis of the LAD and recent
      myocardial infarction. CONCLUSIONS: Coronary occlusion in patients undergoing
      MIDCAB can result in ST segment elevation, followed by reperfusion ventricular
      extrasystoles. The reperfusion arrhythmias were observed in patients showing a
      significant elevation of the ST segment during coronary occlusion; risk factors
      included a preoperative history of arrhythmia, unstable angina, recent MI, and/or
      70% LAD stenosis. The rapid restoration of the control ST segment level and the
      significant increase of cardiac output following coronary reperfusion suggest
      that isoflurane anesthesia may have provided a degree of myocardial protection
      during coronary clamping and reperfusion.

PMID- 11949202
TI  - Sevoflurane vs isoflurane anaesthesia: a study of postoperative mental
      concentration and fine motor movements.
AB  - Ambulatory anaesthesia is a challenging specialty. Often locoregional techniques
      are preferred due to the speedy recovery and short hospital stay. However a
      reasonable number of day-case surgery are performed under general anaesthesia
      where the recovery of cognitive functions are delayed. Therefore we conducted
      this study in order to assess the postoperative mental concentration and fine
      motor movements following isoflurane versus sevoflurane anaesthesia. Twenty adult
      patients were enrolled in the study. They were ASA 1, age 33 +/- 10 yr and weight
      68 +/- 7 kg. They were divided into two groups A and B for isoflurane and
      sevoflurane respectively. After routine monitoring, induction for both groups was
      achieved with propofol, endotracheal intubation was facilitated with atracurium
      and maintenance with either isoflurane or sevoflurane 1 MAC with 50% nitrous
      oxide in oxygen. During the recovery period the cognitive functions were assessed
      using the tracing test equipment where the time error product (TEP) was used as a
      test score. In both groups 30 min after anaesthesia the TEP was 10,000 sec.
      Thirty minutes later the median TEP was 6,316 sec and 10,000 sec in groups A and
      B respectively. Another thirty minutes later, the TEP median was 4,052 sec and
      1,209 sec for groups A and B respectively. Five hours after anaesthesia the TEP
      in both groups became identical but still significantly higher compared with the
      preoperative values. In the present study the TEP was reduced in the sevoflurane
      group 2 hr after anaesthesia from 10,000 sec to nearly 1,000 sec where in the
      isoflurane group it was reduced from 10,000 sec to 4,000 sec. In conclusion,
      sevoflurane anaesthesia resulted in superior recovery of the early TEP scores
      compared to isoflurane but in both groups the late TEP scores were identical. We
      believe that following general anaesthesia in day-case set up the patients should
      refrain from any kind of work that necessitates fine motor movement and mental
      concentration for at least 24 hr postoperatively.

PMID- 11949203
TI  - Use of a lighted flexible catheter as a detector for accidental oesophageal
      intubation through the intubating laryngeal mask: a preliminary study.
AB  - We have evaluated the use of a prototype lighted flexible catheter using the
      transillumination of the light through the soft tissues of the neck, as a
      detector of the accidental oesophageal intubation during the tracheal intubation
      through the intubating laryngeal mask. Two hundred patients undergoing general
      anaesthesia were studied. Accidental oesophageal intubation occurred in 12
      patients (6%) during the first intubating attempt and was diagnosed by noting
      absence of glow on the neck during the tracheal tube advancement and was
      confirmed by capnography. However, 11/12 (92%) of the above patients were finally
      intubated successfully, using the lighted flexible catheter. In one patient
      persistent accidental oesophageal intubation occurred and was classified as
      failure.

PMID- 11949204
TI  - Anaesthesia for morbidly obese patients: a study of haemodynamic changes during
      bariatric surgery.
AB  - BACKGROUND AND AIMS: Morbid obesity with body mass index (BMI) > 40 kg/m2
      requires surgical correction if the diet program fails. Laparoscopic adjustable
      gastric banding (LAGB) (bariatric surgery) is the standard surgical procedure.
      The haemodynamic effects of the typical pneumoperitoneum had been studied but,
      the additional effects of morbid obesity and the consequences of LAGB surgery had
      not. Therefore, we conducted this study to determine the haemodynamic changes
      under anaesthesia during bariatric surgery. MATERIALS AND METHODS: Under general
      anaesthesia, 7 patients (4 males) were studied. Their mean age was 36.2 yr (range
      25-50 yr) and mean BMI was 49.7 kg/m2 (range 39.3-67.3). Besides routine
      monitoring of vital signs, non invasive cardiac output monitor (NICO, Novametrix,
      Wallingford, CT, USA) was used to monitor cardiac output (CO), cardiac index (CI)
      and stroke volume (SV). All the haemodynamic variables were taken at three
      phases: A) after induction of anaesthesia, B) during pneumoperitoneum and C)
      after gas deflation. RESULTS: The mean HR and BP showed significant high values
      during phase B compared to phase A. The mean values of CO were 7.2 +/- 1.1 and
      9.06 +/- 2.6 L/min during phases A and B respectively with significant
      differences. The mean values of SV were 91.1 +/- 12.3 and 123.2 +/- 42.6 ml
      during phases A and B respectively with significant differences. The mean values
      of CI during phases A and B were 3.1 +/- 0.7 and 3.4 +/- 1.09 L/min/m2
      respectively with significant differences. CONCLUSIONS: We have reported high CO
      and CI during pneumoperitoneum, which may be due to increased heart rate induced
      by sympathetic stimulation.

PMID- 11949205
TI  - Pharmacotherapy of tetanus--a review.
AB  - With adequate immunization, tetanus caused by the gram-positive anaerobic cocci,
      clostridium tetani, is a preventable disease. In treating C. tetani infection,
      Metronidazole as an antibiotic is more effective than Penicillin G since it is a
      GABA antagonist. Agents used to control spasm and rigidity should have little
      effect on the level of consciousness, respiration and blood pressure. The drug of
      choice for treating spasm and rigidity is benzodiazepine, a GABA agonists. Large
      doses of benzodiazepines may be required to overcome the spasm and are safe.
      Baclofen is another GABA agonist, which has been tried as an alternative to
      benzodiazepine with moderate success. Clinical experience with dantrolene sodium
      is limited. Magnesium with its unique properties on the neuromuscular junction
      and sympathetic system has been used to treat both spasms and autonomic
      dysfunction with limited success. Neuromuscular blocking drugs are indicated
      depending on the severity of spasms. Neuromuscular blocking drugs with steroid
      molecule should be avoided in view of prolonged weakness. No drug has
      consistently proven to be effective in the treatment of autonomic dysfunction.
      Beta-blockers, variation of and beta blockers, opioids, clonidine, magnesium,
      spinal and epidural anaesthesia have been tried with varying success. Beta
      blockers should be used with caution as they have been implicated in the deaths
      of some patients with autonomic dysfunction.

PMID- 11949206
TI  - Anaesthesia for bilateral mastectomy in a Jehovah's Witness patient with epilepsy
      and review of alternatives to homologous blood transfusion.
AB  - The anaesthetic management of a Jehovah's Witness patient for bilateral
      mastectomy for carcinoma of the breast is described. The patient is also a known
      epileptic patient who developed fits the night before surgery. Surgery was re
      scheduled for one week later to allow control of the epilepsy. Surgery was
      carried out under general anaesthesia. The patient refused blood transfusion.
      Modified normovolaemic haemodilution was the alternative to homologous blood
      transfusion used in the patient. This was safe except for the post-operative
      morbidity due to severe anaemia in the patient. The surgical outcome was good.
      The safety of not transfusing blood in Jehovah's Witness patient for surgical
      procedures for which blood transfusion is needed is well illustrated by this
      case. A review of alternatives to homologous blood transfusion is done.

PMID- 11949207
TI  - The rhyme and reason behind hospital accreditation.

PMID- 11949208
TI  - Management of malaria in Thailand.
AB  - The purpose of treatment for uncomplicated malaria is to produce a radical cure
      using the combination of: artesunate (4 mg/kg/day) plus mefloquine (8 mg/kg day)
      for 3 days: a fixed dose of artemether and lumefantrine (20/120 mg tablet) named
      Coartem (4 tablets twice a day for three days for adults weighing more than 35
      kg): quinine 10 mg/kg 8-hourly plus tetracycline 250 mg 6-hourly for 7 days (or
      doxycycline 200 mg as an alternative to tetracycline once a day for 7 days) in
      patients aged 8 years and over: Malarone (in adult 4 tablets daily for 3 days).
      In treating severe malaria, early diagnosis and treatment with a potent
      antimalarial drug is recommended to save the patient's life. The antimalarial
      drugs of choice are: intravenous quinine or a parenteral form of an artemisinin
      derivative (artesunate i.v./i.m. for 2.4 mg/kg followed by 1.2 mg/kg injection at
      12 and 24 hr and then daily for 5 dayss; artemether i.m. 3.2 mg/kg injection
      followed by 1.6 mg/kg at 12 and 24 hrs and then daily for 5 days; artemether i.m.
      (Artemotil) with the same dose of artemether or artesunate suppository (5 mg/kg)
      given rectally 12 hourly for 3 days. Oral artemisinin derivatives (artesunate,
      artemether, and dihydroartemisinin with 4 mg/kg/day) could replace parenteral
      forms when patients can tolerate oral medication. Oral mefloquine (25 mg/kg
      divided into two doses 8 hrs apart) should be given at the end of the artemisinin
      treatment course to reduce recrudescence.

PMID- 11949209
TI  - Isolation and characterization of a cDNA encoding a mammalian cathepsin L-like
      cysteine proteinase from Acanthamoeba healyi.
AB  - We have cloned a cDNA encoding a cysteine proteinase of the Acanthamoeba healyi
      OC-3A strain isolated from the brain of a granulomatous amoebic encephalitis
      patient. A DNA probe for an A. healyi cDNA library screening was amplified by PCR
      using degenerate oligonucleotide primers designed on the basis of conserved amino
      acids franking the active sites of cysteine and asparagine residues that are
      conserved in the eukaryotic cysteine proteinases. Cysteine proteinase gene of A.
      healyi (AhCP1) was composed of 330 amino acids with signal sequence, a proposed
      pro-domain and a predicted active site made up of the catalytic residues. Cys25,
      His159, and Asn175. Deduced amino acid sequence analysis indicates that AhCP1
      belong to ERFNIN subfamily of C1 peptidases. By Northern blot analysis, no direct
      correlation was observed between AhCP1 mRNA expression and virulence of
      Acanthamoeba, but the gene was expressed at higher level in amoebae isolated from
      soil than amoeba from clinical samples. These findings raise the possibility that
      Ahcp1 protein may play a role in protein metabolism and digestion of phagocytosed
      bacteria or host tissue debris rather than in invasion of amoebae into host
      tissue.

PMID- 11949210
TI  - A riboprinting scheme for identification of unknown Acanthamoeba isolates at
      species level.
AB  - We describe a riboprinting scheme for identification of unknown Acanthamoeba
      isolates at the species level. It involved the use of PCR-RFLP of small subunit
      ribosomal RNA gene (riboprint) of 24 reference strains by 4 kinds of restriction
      enzymes. Seven strains in morphological group I and III were identified at
      species level with their unique sizes of PCR product and riboprint type by Rsa I.
      Unique RFCP of 17 strains in group II by Dde I, Taq I and Hae III were classified
      into: (1) four taxa that were identifiable at the species level, (2) a subgroup
      of 4 taxa and a pair of 2 taxa that were identical with each other, and (3) a
      species complex of 7 taxa assigned to A. castellanii complex that were closely
      related. These results were consistent with those obtained by 18s rDNA sequence
      analysis. This approach provides an alternative to the rDNA sequencing for rapid
      identification of a new clinical isolate or a large number of environmental
      isolates of Acanthamoeba.

PMID- 11949211
TI  - Identification of newly isolated Babesia parasites from cattle in Korea by using
      the Bo-RBC-SCID mice.
AB  - Attempts were made to isolate and identify Korean bovine Babesia parasite. Blood
      samples were collected from Holstein cows in Korea, and Babesia parasites were
      propagated in SCID mice with circulating bovine red blood cells for isolation.
      The isolate was then antigenically and genotypically compared with several
      Japanese isolates. The Korean parasite was found to be nearly identical to the
      Oshima strain isolated from Japanese cattle, which was recently designated as
      Babesia ovata oshimensis n. var. Haemaphysalis longicornis was the most probable
      tick species that transmitted the parasite.

PMID- 11949212
TI  - Vector competence of Anopheles lesteri Baisas and Hu (Diptera: Culicidae) to
      Plasmodium vivax in Korea.
AB  - Three anopheline mosquitoes in Korea were studied for their abilities as vectors
      for Plasmodium vivax. The female mosquitoes of Anopheles lesteri, An. pullus and
      An. sinensis were allowed to suck malaria patient blood until fully fed, and they
      were then bred for 2 weeks to develop from malaria parasites to sporozoites. The
      result from the above confirmed the sporozoites in one An. lesteri of one
      individual and five An. sinensis of six individuals. We also confirmed that An.
      sinensis was the main vector to transmit malaria and An. lesteri as well as An.
      sinensis were able to carry Korean malaria parasites. Therefore, we propose that
      diversified study is needed to manage malaria projects.

PMID- 11949214
TI  - Specific bovine antibody response against a new recombinant Cryptosporidium
      parvum antigen containing 4 zinc-finger motifs.
AB  - A Cryptosporidium parvum sporozoite and oocyst lambda gt11 cDNA library was
      screened with a hyperimmune rabbit serum that was developed against insoluble
      fragments of ultrasonicated oocysts. A clone named Cp22.4.1 encoding a protein of
      231 amino acids with 4 zinc-finger domains characterized by a Cys-X2-Cys-X4-His
      X4-Cys motif was isolated and characterized. There was a complete match between
      the sequencing data of the coding region of Cp22.4.1 and the corresponding gene
      at chromosomal level. Cloning in a pBAD-TOPO-TA expression vector permitted to
      evaluate the antigenicity of the recombinant His-tagged antigen. This antigen was
      recognized by 2 out of 5 sera from Cryptosporidium immune calves and not by sera
      from parasite naive animals.

PMID- 11949213
TI  - Late season commercial mosquito trap and host seeking activity evaluation against
      mosquitoes in a malarious area of the Republic of Korea.
AB  - Field trials evaluating selected commercially available mosquito traps variously
      baited with light, carbon dioxide, and/or octenol were conducted from 18-27
      September 2000 in a malarious area near Paekyeon-ri (Tongil-Chon) and Camp
      Greaves in Paju County, Kyonggi Province, Republic of Korea. The host-seeking
      activity for common mosquito species, including the primary vector of Japanese
      encephalitis, Culex tritaeniorhynchus Giles, was determined using hourly
      aspirator collections from a human and propane lantern-baited Shannon trap during
      hours when temperatures exceeded 15 degrees C. The total number of mosquitoes and
      number of each species captured during the test was compared using a block
      design. Significant differences were observed for the total number of mosquitoes
      collected, such that, the Mosquito MagnetTM with octenol > Shannon trap > ABC
      light trap with light and dry ice > Miniature Black Light trap (manufactured by
      John W. Hock) > or = New Jersey Trap > ABC light trap with light only.
      Significant differences in numbers collected among traps were noted for several
      species including: Aedes vexans (Meigen), Anopheles lesteri Baisas and Hu. An.
      sinensis Weidemann. An. sineroides Yamada, An. yatsushiroensis Miyazaki, Culex
      pipiens pallens Coquillett L., Cx. orientalis Edwards and Cx. tritaeniorhynchus.
      Host-seeking activity for most common species showed a similar bimodal pattern.
      Results from these field trap evaluations can significantly enhance current
      vector and disease surveillance efforts especially for the primary vector of
      Japanese encephalitis, Cx. tritaeniorhynchus.

PMID- 11949215
TI  - Epidemiological study of clonorchiasis and metagonimiasis along the Geum-gang
      (River) in Okcheon-gun (county), Korea.
AB  - The endemic status of clonorchiasis and metagonimiasis along the Geum-gang
      (River) in Okcheon-gun (County) in Korea was examined. From February to December
      2000, stools of total 1,081 inhabitants living in 5 villages were examined. Each
      stool specimen was examined by both the cellophane thick smear method and the
      formalin-ether sedimentation technique. Egg-positive cases were further analyzed
      by Stoll's egg-counting technique, and praziquantel was administered to positive
      cases. The egg-positive rates for Clonorchis sinensis and Metagonimus species
      were 9.3% and 5.5%, respectively, and the double infection rate was 3.5%. The
      numbers of eggs per gram (EPG) of feces of C. sinensis and Metagonimus sp. were
      918 +/- 1,463 and 711 +/- 947, respectively. The egg-positive rates for C.
      sinensis and Metagonimus sp. in the riverside area were 14.2% and 8.4%,
      respectively, which were significantly higher than those of the inland area (3.2%
      and 1.7%, respectively). The egg-positive rates of C. sinensis and Metagonimus
      sp. in males (16.7% and 10.0%) were significantly higher than those of females
      (3.5% and 1.8%). However, there were no significant differences of EPG values
      between localities and sexes. The prevalence of clonorchiasis and metagonimiasis
      in this survey was significantly lower than that in the previous reports.
      However, there is still a high prevalence of infection with C. sinensis and
      Metagonimus sp. in this region, especially in the riverside area.

PMID- 11949216
TI  - [Spontaneous bacterial peritonitis in the Czech Republic].
AB  - The objective of the study was to assess the prevalence and more detailed data
      pertaining to the incidence of spontaneous bacterial peritonitis (SBP) in the
      Czech Republic. The authors examined 99 patients with cirrhosis of the liver and
      ascites. SBP was diagnosed in a high percentage--35 patients, i.e. 35.4%. It was
      found more frequently in patients with an alcoholic etiology of cirrhosis who had
      a history of subfebrile and febrile temperatures and increasing trend of ascites.
      For the diagnosis the increase of leucocytes in serum and C reactive protein
      levels may prove useful. Lower values of total protein and albumin in ascites
      predispose to the development of this infection. Reduction of the number of
      thrombocytes in the group of patients with SBP indicates the influence of portal
      hypertension in the etiology of this disease.

PMID- 11949218
TI  - [Early diagnosis and reasons for not administering thrombolytic therapy in acute
      myocardial infarct].
AB  - In Slovakia we are lacking data on early (before examination of serum markers of
      myocardial necrosis) pertaining to thrombolytic treatment (TLL) which is
      inevitable in case of acute myocardial infarction (AIM) as well as data on the
      reasons why TLL is not implemented. This why the authors analyze the results of
      completed comprehensive project Audit concerned with diagnostic and therapeutic
      procedures in patients with acute coronary syndromes during the pre-hospital and
      hospital stage (AUDIT). The investigation was a perspective multi-centre study.
      Data were collected from 3123 patients with AIM in 66 departments (in 64 health
      institutions) during Sept. 16 1997 till Sept. 15 1998. The group included
      patients admitted within 96 hours after the development of complaints with the
      diagnosis or suspicion of AIM and discharged with the diagnosis of a
      first/repeated AIM. Early diagnosis of AIM was made in 1736 (55.6%) patients. In
      the AUDIT study TLL was assessed in 1074 (34.6%) patients. A marked difference
      between the number of candidates for TLL and the number of patients with TLL
      where TLL was implemented requires that in analyses of TLL in patients with AIM
      attention should be paid also to reasons why it was not implemented. The most
      frequent cause why TLL was nor implemented was late admission of the patient to
      hospital (in patients who attended hospital < 6 hours, TLL was not implemented in
      48.5%, after admission between 6 and 12 hours in 70% and in patients admitted >
      12 hours in as many as 90.8% patients), equivocal indication of TLL (in 29.9%
      patients) and contraindications (in 16.1% patients). The presented results are
      priority data on the early diagnosis of AIM and reasons why TLL was not
      implemented. It is part of data essential needed for elaboration of a (national)
      programme of better care (management) of patients with AIM taking into account
      also economic factors.

PMID- 11949217
TI  - [Serum ferritin, LDL oxidation and risk factors for atherogenesis in healthy
      offspring of hypertensive patients].
AB  - Iron is an important factor in the process of oxidation stress and atherogenesis
      which is as a rule potentiated in subjects with the insulin resistance syndrome.
      Hypertension is one of the main components of this syndrome. Ferritin due to its
      relationship with impaired insulin sensitivity becomes a candidate for a new
      indicator of insulin resistance. The subject of the present study was to assess
      whether we shall find in young healthy offspring of hypertensive parents changes
      in the ferritin level, oxidizability of LDL and whether these are related to
      parameters of glucose tolerance, insulin secretion and sensitivity. Twelve young
      (27 +/- 3.6 years) non-obese, normotesive offspring of hypertensive parents were
      compared with a group of 14 controls. Glucose tolerance, insulin secretion and
      sensitivity were examined by means of a hyperglycaemic clamp and oGTT. As to the
      ferritin level, the offspring of hypertensive parents did not differ
      significantly from controls, differences were not fond in the oxidizability of
      LDL-C. The glucose tolerance was comparable in the two groups. Offspring of
      hypertensive parents had however a significantly higher insulin and C peptide
      level when using the clamp and during the glucose tolerance test (p < 0.05), and
      a reduced insulin sensitivity (p < 0.05). The negative correlation between the
      index of insulin sensitivity and ferritin suggests that ferritin could be
      associated with the syndrome of insulin resistance.

PMID- 11949219
TI  - [Detection of cytomegalovirus infection with the polymerase chain reaction and
      antigenemia after allogenic bone marrow transplantation].
AB  - The objective of the work was to evaluate the frequency and time of incidence of
      cytomegaloviral (CMV) infection and disease in patients after allogeneic bone
      marrow transplantation (BMT). One hundred patients were followed up (70 with a
      related and 30 with an unrelated donor), who had transplantations during the
      period between XI/1996-XI/2000. METHODS USED: nested-PCR (MIE-gene) and
      antigenaemia (antigen pp65). Active CMV infection was proved in antigenaemia > or
      = 5 positive cells or in two consecutive positive PCR. The CMV syndrome was
      assessed in confirmed CMV infection and otherwise inexplicable febrile conditions
      and/or a drop of haemogram values. For the diagnosis of CMV pneumonia the
      clinical picture was needed, evidence of active CMV infection and on the X-ray of
      the lungs interstitial pneumonia. In 33 patients both methods were used, in 67
      only PCR. The first positive test appeared 6-321 days after BMT (median +/- 49
      days). CMV infection was proved in 44% cases, CMV syndrome in 30% and CMV
      pneumonia in 4%. In patients with a related donor CMV infection was found in
      34.3%, CMV syndrome in 22.9%, CMV pneumonia in 1.4%. After unrelated donor BMT
      CMV infection was recorded in 66.7%, CMV syndrome in 46.7% and CMV pneumonia in
      10% patients. Two patients died from CMV pneumonia. CMV pneumonia was diagnosed
      57-115 days after BMT (median +/- 68 days. The risk of CMV infection is high in
      both groups of patients, in particular in patients after unrelated donor BMT
      (66.7%). As far as the development of CMV pneumonia was concerned, the mortality
      in the authors' group was 50%.

PMID- 11949220
TI  - [Diagnosis and therapy of gestational diabetes mellitus].
AB  - In 1999-2000 at the Medical Clinic Motol Faculty Hospital in collaboration with
      the Gynaecological Clinic of the Hospital a group of 55 pregnant women with the
      diagnosis of gestational diabetes (GDM) were followed up. The objective of the
      investigation was to find out how in the investigated area (detachment area of
      the Gynaecological and Obstetric Clinic Motol Faculty Hospital) GDM is diagnosed
      at present, how it is treated and what is the percentage of perinatal morbidity
      in the investigated group. The mean age of the investigated women was 32.3 +/-
      4.5 years. The presence of risk factors for the development of GDM was found in
      59.8% of the examined women. 65.7% women had a positive gynaecological case
      history. GDM was detected most frequently during the 30th week of pregnancy, in
      25% women in the 35th and later week of gestation. In 52% the diagnosis of GDM
      was established only on hospital admission on account of complications of
      pregnancy. The mean HbA1C level during detection of gestational diabetes was 6.81
      +/- 0.41%. The majority of women -91.1%--were treated by diet, 8.9% women had
      insulin treatment. The prevalence of diabetic foctopathy was 48.3%. The mean
      weight of the offspring of diabetic mothers was 3350 g +/- 248 g, the mean length
      was 49.6 +/- 6.3 cm. No stillbirth was recorded. One infant suffered from an
      inborn developmental defect (morbus Down). The results provide evidence not only
      of late diagnosis of GDM (after the 28th week of gestation) but also of
      inadequate screening in the field, as GDM is frequently detected only during
      complications of pregnancy.

PMID- 11949221
TI  - [Echocardiography after orthotopic heart transplantation].
AB  - One of the most serious complications after orthotopic transplantation of the
      heart (OTH) is graft rejection. Its early detection can help successful control.
      The diagnostic gold standard is myocardial biopsy, it is however not always
      supreme. We tried to find out whether some modern echocardiographic methods can
      provide further valuable information. At the same time we were concerned with the
      follow up of basic variables of the circulation and echocardiographic indicators
      of left ventricular function. MATERIAL AND METHODS: The authors examined
      repeatedly 22 patients where in 1998-2000 OTH was performed, who did not have an
      acute severe rejection, who had at least one myocardial biopsy between the first
      and second month after OTH without signs of rejection and who were easily
      examined by echocardiography. In addition to the standard follow up according to
      a routine pattern they were subjected to clinical and echocardiographic
      examination during the 1st-2nd month after OTH, 6 months after the first
      examination and one year after the second examination. Classical
      echocardiography, acoustic densitometry and Doppler tissue examination of the
      movement of the mitral ring were used. RESULTS: The patients had throughout the
      investigation period clinical cardiological complications. Between the first and
      second examination the systolic pressure rose from 125.4 +/- 9.5 to 135.4 +/-
      13.5 mm Hg (p < 0.05), the diastolic pressure from 79.6 +/- 8.2 to 86.4 +/- 9.5
      mm (p < 0.05), during the third examination it dropped again to original values.
      During the follow up no significant differences developed in indicators of
      classical echocardiography, acoustic densitometry and Doppler tissue
      echocardiography. Of 22 patients however myocardial biopsy of the right ventricle
      proved rejection only in two. In those the authors did not observe any
      echocardiographic changes during rejection. In one patient who died
      echocardiography revealed a decline of left ventricular function and a non
      specific bioptic finding, and on necropsy severe cellular vascular rejection.
      CONCLUSIONS: Blood pressure rises early in some patients after OTH, it is
      therefore important to monitor it carefully and to administer early and
      systematic treatment of hypertension. In non-complicated patients the
      echocardiographic findings did not change. Because of the low number of
      rejections the authors were not able to prove the importance of some new
      echocardiographic methods. In view of discrepancies between methods in some
      patients with rejection a comprehensive diagnostic approach is still necessary:
      myocardial biopsy supplemented by further examinations, in particular
      echocardiographic ones.

PMID- 11949222
TI  - [Thyrotoxic heart disease. Part II--aspects of treatment of thyrotoxicosis with
      cardiac involvement].
AB  - In the treatment of the thyrotoxic heart a radical, early thyroeliminating
      procedure should have preference. As the method of first choice a single
      administration of a whole calculated dose of I131 is recommended without previous
      medicamentous preparation up to 25-30 mCie which can be administered also in the
      out-patient department, with subsequent immediate treatment with thyrostatics and
      beta-blockers till remission of thyrotoxicosis is achieved (6-12 weeks). Total
      strumectomy after medicamentous preparation in remission of thyrotoxicosis is
      preferred in large multinodular, iodinated patients and in solitary toxic adenoma
      where however also partial STE (lobectomy) is possible and radioiodine is
      equivalent. Its dosage in toxic adenoma and nodular goitre is however in general
      higher than in diffuse goitre but the incidence of late postadministration
      hypothyroidism is lower. Fibrillation arrhythmia usually (in ca 60%) recedes
      spontaneously with the assistance of beta-blockers in remission of
      thyrotoxicosis. If this does not occur, pharmacological or electric cardioversion
      is necessary after anticoagulation preparation, because persistence of FA is an
      important risk factor of cardiac failure and thromboembolic complications.
      Eurhythmia then usually lasts as long as remission of thyrotoxicosis persists or
      there is no overdosage of substitution doses of T4 during treatment of
      hypothyroidism which develops after thyroelimination treatment. Amiodarone is
      unsuitable, even contraindicated, for treatment of fibrillation arrhythmia in
      thyrotoxic heart.

PMID- 11949223
TI  - [Non-specific immune responses in patients with chronic diabetic foot syndrome
      and chronic bacterial infection].
AB  - Chronic bacterial ulcers infection is a frequent cause of non-healing diabetic
      foot. The major factors of a non-specific immune response are phagocytic cells
      including polymporphonuclear (PMN) leukocytes, and humoral systems (complement).
      PMN leukocytes remove microorganisms by phagocytosis a part of it is
      intracellular killing and degradation in a process requiring energy and
      associated with "respiratory burst". The aim of our study was to assess non
      specific immune response in patients with diabetic foot syndrome and chronic
      bacterial infection. 30 patients treated over one month with antibiotics for an
      infected diabetic foot in our foot clinic had significantly lower values of
      "oxidative burst" of PMN leukocytes in basal state (396 +/- 228 vs. 574 +/- 337,
      p < 0.05) in comparison with 25 matched healthy controls. There were no
      significant differences neither in the count of active phagocyting PMN leukocytes
      and their initial phagocytic activity nor in the humoral component of non
      specific immunity (in circulating immunocomplexes, C3 and C4 components of
      complement) between both groups. The results of our study show a slightly altered
      non-specific immune response in patients with diabetic foot syndrome and chronic
      bacterial infection.

PMID- 11949224
TI  - [Disorders of the pulmonary lymphatic system].
AB  - The pulmonary lymphatic system plays an important role in lung perfusion
      homeostasis. Congenital errors of lymphatic vessel development lead to primary
      pulmonary lymphatic disorders (lymphangiomas, lymphangiectasis, lymphatic
      dysplasia syndromes). Acquired disorders of the pulmonary lymphatic system occur
      in a variety of clinical settings (ranging from trauma to cancer) and may lead to
      serious pulmonary disease. Because of their scarcity and confusing and
      inconsistent use of terminology, these conditions are often misdiagnosed. Their
      management is difficult.

PMID- 11949225
TI  - [Sudden cardiac death (part 1].
AB  - Sudden cardiac death is a sudden unexpected non-violent death for cardiac reasons
      which according to the majority of authors occurs within one hour after the
      development of symptoms of acute impairment of health. This syndrome is a major
      problem of contemporary medicine with a very adverse prognosis. The authors
      analyze the epidemiology, causes, influence of the external environment, basic
      arrhythmogenic mechanisms and prognosis of sudden death. Examination methods of
      this clinical condition are evaluated from the aspect of their application in the
      risk stratification of patients.

PMID- 11949226
TI  - [Late recurrence of Hodgkin's disease 20 years after initial diagnosis. Personal
      observation of two cases and a literature review].
AB  - Most patients with Hodgkin's disease (especially early stage disease) are
      successfully treated using modern treatment modalities. Disease relapse usually
      occurs within the first three years after initial therapy. Late relapses of
      Hodgkin's disease, occurring after 10 years or even later, are rare (0.6% of
      cases only). Their biological behaviour is different from that of early relapses,
      resembling primary disease. The question whether very late relapses represent a
      second primary disease in patients with a genetic predisposition to Hodgkin's
      disease rather than a relapse of the original disease remains the subject of much
      discussion. We report here two cases of very late relapses of Hodgkin's disease,
      occurring twenty years after initial treatment. Both patients were now treated by
      intensified chemotherapy, escalated BEACOPP. In one case, this was followed by
      radiotherapy of the residual tumor (40 Gy). Both patients are in complete
      remission.

PMID- 11949227
TI  - [History of the treatment of essential hypertension--part II].

PMID- 11949228
TI  - [Importance of determination of serum beta-2-microglobulin levels in patients
      with Hodgkin's lymphoma].
AB  - The authors evaluated retrospectively in a group of 69 adult patients with
      Hodgkin's lymphoma the relationship between the beta-2-microglobulin serum level,
      basic demographic parameters (age, sex) and factors characterizing the extent
      (stage III and IV, "bulk" or mediastinal mass, number of affected areas of lymph
      nodes) and activity of the tumour (presence of B-symptoms, red cell sedimentation
      rate, haemoglobin, albumin and lactate dehydrogenase level, number of leucocytes
      and lymphocytes). They analyzed also the possible prognostic impact of beta-2
      microglobulin on the therapeutic response risk of relapse and patient's survival.
      Methods of univariant statistical analysis confirmed the correlation of beta-2
      microglobulin level with all investigated metric parameters of patients (advanced
      age, number of affected nodes, red cell sedimentation rate and lactate
      dehydrogenase level, lower albumin, haemoglobin level, numbers of leucocytes and
      lymphocytes). In multivariant analysis however the only independent metric
      markers significantly associated with an elevated protein level were more
      advanced age of the patients (P = 0.0002) and a lower number of leucocytes (P =
      0.05). The values of beta-2-microglobulin was not influenced by the extent of the
      tumour (stage III and IV, "bulk" or mediastinal mass, higher number of affected
      areas of lymph nodes). Significantly more frequently elevated protein values were
      recorded in patients with manifestations of B symptoms associated with the
      diagnosis (P = 0.0003). Multivariant analysis did not prove the importance of the
      serum level of beta-2-microglobulin as a prognostic factor in the sense of
      predicted remission, development of a relapse or death in conjunction with
      progression of Hodgkin's lymphoma.

PMID- 11949229
TI  - [Prolactin levels before and after stimulation with thyroliberin in primary
      hypothyroidism].
AB  - The authors examined the concentration of thyrotropic hormone (TSH) and prolactin
      (PRL) before and after stimulation with synthetic thyroliberine (0.2 mg TRH i.v.)
      in a group of 72 women with primary hypothyroidism (mean age 45 years, range 17
      69 years) and 12 controls (mean age 35 years, range 17-49 years). According to
      the total thyroxin concentrations (TT4) and TSH they divided the group into three
      smaller subgroups: developed primary hypothyroidism (n = 8, mean age 50 years,
      TT4 < 65 nmol/l, basal TSH concentration > 15.0 mIU/l nmol/l), subclinical
      hypothyroidism, severe grade (n = 23, mean age 36 years, TT4 > 65 nmol/l, basal
      TSH concentration < 4.5 mIU/l), subclinical hypothyroidism mild degree (n = 39,
      mean age 42 years, TT4 > 65 nmol/l, basal TSH concentration < 4.5 mIU/l, TSH
      after TRH stimulation > 25 mIU/l). Mean basal PRL concentrations were in all
      three patient groups significantly higher than in the control group (P < 0.01)
      but mutually they did not differ significantly. Poststimulation PRL
      concentrations were also significantly higher than in controls however the values
      in developed hypothyroidism were significantly higher than in subclinical
      patients. No correlation was found between TSH and PRL concentrations.

PMID- 11949230
TI  - Double duty: nurses put stamp on legislation in Maine.

PMID- 11949231
TI  - Under the Tucson sun. Defying anti-union climate, southern Arizona nurses stand
      up for patients, themselves.

PMID- 11949232
TI  - Why can't we be friends? How management reorganizes work and manipulates nurses.

PMID- 11949233
TI  - Medicare's spin cycle.

PMID- 11949234
TI  - New voice for caregivers. The American Association of Registered Nurses is born.

PMID- 11949235
TI  - New questions about electromagnetic fields.

PMID- 11949236
TI  - Upper extremity nerve entrapments.
AB  - Nerve entrapment occurs when a nerve is "trapped" by pathologic changes in the
      tissues through which the nerve passes. Nerve entrapments occur more frequently
      in the upper than in the lower extremities and are characterized by pain and
      paresthesias, with or without sensory and/or motor nerve loss. The major
      pathologies related to upper extremity nerve entrapment involving the cervical,
      thoracic, shoulder, elbow, and wrist areas are discussed in this article.

PMID- 11949238
TI  - Managing neural tissue injury in combined vertebral column-spinal cord injury.
AB  - Orthopaedic, neurosurgical, and trauma nurses all care for patients who have
      sustained a spinal cord injury (SCI) and are challenged to address care issues
      related to spinal stability as well as neurologic function. Advances in the
      understanding of the pathobiology of SCI have given rise to a three-tiered, time
      sensitive approach to intervention designed to optimize functional recovery.
      Immediately after injury, pharmacologic strategies dominate. They are generally
      intended to limit progression of the initial injury, preserve existing neurologic
      function, and create the nidus for future regeneration. This article reviews the
      current standard of care with respect to hyperacute neuroprotection after blunt
      SCI in adults. After a synopsis of selected concepts in the pathophysiology of
      injury and pharmacology, clinical trial results will be presented, followed by a
      discussion of the nursing implications associated with the use of high-dose
      methylprednisolone neuroprotective therapy.

PMID- 11949237
TI  - 'Mom & me' and healthy bones. An innovative approach to teaching bone health.
AB  - Poor bone health may lead to osteoporosis and an increased risk for fracture
      later in life. Peak bone mass, which is one of the most important determinants of
      developing osteoporosis, is accrued largely by the age of 18. Therefore, actions
      to maximize peak bone mass need to be taken during the childhood years. Because
      80% of those affected with osteoporosis are women, it is important that young
      girls receive information on how to reduce their risk for this disorder. The
      authors have developed an educational program to help young girls learn about
      bone health. The specifics of the program are described in this article.

PMID- 11949239
TI  - A randomized, controlled trial comparing compression bandaging and cold therapy
      in postoperative total knee replacement surgery.
AB  - PURPOSE: To examine the difference between compression bandaging and cold therapy
      after total knee arthroplasty. SAMPLE: Eighty-four postoperative, unilateral,
      total knee replacement, surgical clients. PROCEDURE: Clients were randomized into
      two groups: those receiving compression bandaging, and those receiving cryo-pad
      technology. Subjects were assessed for total length of stay, blood loss, blood
      transfusion, swelling, flexion, pain, and opiate use. FINDINGS: Unlike other
      studies, the results of these data showed no significant differences between
      groups on the measured outcomes. A simple cost benefit analysis shows that the
      compression bandage is cheaper and more labor efficient than the cold therapy as
      delivered by cryo-pad technology.

PMID- 11949240
TI  - Improving productivity through the use of portable radios.
AB  - Orthopaedic practices are under increasing pressure to improve productivity in
      the ambulatory setting. Best practice use of portable radios or walkie-talkies
      help to achieve a near 50% reduction in patient visit time without reducing the
      time spent with the care provider. More patients may be seen or the same number
      in less time. Increased staff communication saves wasted steps and decreases the
      response time in patient emergencies. A variety of radios and accessory equipment
      may be needed to meet the needs of each user and to overcome any structural
      interference. Successfully instituting this practice change involves time-motion
      studies, assigning a project manager, and full leadership support. The emission
      of radio frequency waves by portable radios or their transmitting power may
      interfere with implanted pacemakers or external medical equipment. But the risk
      is low when radios are used away from individual patients.

PMID- 11949241
TI  - Developing a professional portfolio in nursing.
AB  - A professional portfolio is a collection of carefully selected materials that
      document the nurse's competencies and illustrate the expertise of the nurse.
      Since a portfolio is developed over time, it also provides a way of monitoring
      professional development. By periodically reviewing the portfolio, nurses can
      assess their progress in meeting personal and professional goals and can better
      plan their careers in nursing. This article describes professional portfolios,
      their uses in nursing, and how to develop and maintain one.

PMID- 11949242
TI  - Adherence revisited: the patient's choice.
AB  - Adherence to treatment is an age-old issue in the health care provider-patient
      relationship. Although findings show that adherence has the potential to increase
      the efficacy of a treatment, is that the only consideration when examining the
      ethical questions surrounding adherence? What if the competent adult patient
      chooses not to adhere? The purpose of this paper is to examine the patient's
      choice to not adhere to a prescribed therapy. The author uses a hypothetical case
      as a way to identify and to challenge the assumptions underlying traditional
      adherence models.

PMID- 11949243
TI  - [Specific features of the epidemiology of the enteric infections in the Kovrov
      district of the Vladimir region].

PMID- 11949244
TI  - [Circulation of tick-borne encephalitis virus in Armenia].

PMID- 11949245
TI  - [V.D. Beliakov and Russian epidemiology (on 80-th anniversary)].

PMID- 11949247
TI  - [Ultrastructure of Yersinia pseudotuberculosis in the process of their reversible
      transition into the dormant (non-culturable) state in association with blue-green
      algae].
AB  - The ultrastructural organization of Y. pseudotuberculosis in the process of the
      transition of vegetative cells into the dormant (noncultivable) state in
      interaction with blue-green algae of the species Anabaena variabilis was studied
      by the method of transmission electron microscopy. The use of type specific Y.
      pseudotuberculosis serum made it possible to identify Y. pseudotuberculosis cells
      in the bacterial association and to find out whether their antigenic properties
      remained intact in time. The dormant forms of Y. pseudotuberculosis, recultivated
      by passage through the axenic culture of unfusoria (Tetrahymena pyryformis), were
      also studied with the use of electron microscopy. The revertants were found to be
      at different stages of restoration of their typical morphological characteristics
      and antigenic properties were partially retained. The fine structure of Y.
      pseudotuberculosis cells in the initial culture was shown to be similar to that
      of the revertants of dormant forms, morphological criteria of the dormant cell
      ultrastructure were established. The cyclic processes of reversible transition
      from vegetative forms to dormant ones in bacterial populations under the
      influence of hydrobios is regarded as an adaptive mechanism of their existence in
      the environment.

PMID- 11949246
TI  - [Interactions of certain sapronotic infection pathogens in mixed cultures on a
      solid medium at different temperatures].
AB  - Under experimental conditions within the time limit of 21-35 days the causative
      agents of sapronotic infections in binary cultures, grown on a solid medium at 37
      degrees C, 25-27 degrees C and 6-8 degrees C, interacted with one another
      transbiotically and through contact, their interactions having the character of
      amensalism, commensalisms-amensalism, competitive equilibrium, antibiosis.
      Irrespective of the initial density, a change in the species composition was
      observed, one of them playing the dominating role. At 37 degrees C mutual
      antagonism of Yersinia pseudotuberculosis and Pseudomonas aeruginosa killed both
      cultures. P. aeruginosa cells were also killed when cultivated at 37 degrees C
      jointly with Listeria monocytogenes, the most resistant species under
      experimental conditions. While studying the character of microorganisms
      interactions the method of contacting cultures on a solid medium was shown to
      give more information in comparison with the "cross-strip" method. Possible
      interspecific relationships between the causative agents of sapronotic infections
      under natural conditions are discussed.

PMID- 11949248
TI  - [Cyclic morbidity of certain natural foci infections in the Russian Federation].
AB  - A special search program for finding out hidden periodicity was used; such
      program made it possible to put in order the apparently chaotic sequence of
      numerical data that are summed up to form the resulting curve, the latter
      reflecting the actual dynamics of the epidemic process. The cyclic character of
      morbidity in tick-borne encephalitis, hemorrhagic fever with the renal syndrome
      (HFRS), tularemia and leptospirosis among the population of Russia for the last
      45-54 years was revealed. In tick-borne encephalitis cycles lasting 17-18 years
      with secondary wave having the period of 3-4 years were found out. In HFRS the
      main cycle lasts for 16 years and has secondary rises every 3-4 years. In
      tularemia the main cycles last for 17 years; secondary rises and drops in
      morbidity were also found to occur every 3-4 years. In leptospirosis regular
      rises and drops in morbidity were found to occur every 4-5 years.

PMID- 11949249
TI  - [Specific features of the typhoid fever epidemic process in organized
      collective].
AB  - During the chronic water epidemic of typhoid fever in Tajikistan in 1996-1997
      specific features of the epidemic process dynamics in groups of servicemen were
      studied in several cities. The infective agent was proved to be transmitted by
      the alimentary route and through everyday contacts, the water route of
      transmission playing the most important role. The early clinical and
      epidemiological signs of the water outbreak of typhoid fever and the risk factors
      were established. The clinical and epidemiological aspects of vaccination were
      analyzed.

PMID- 11949250
TI  - [Electron microscopy study of bacterial adhesiveness].
AB  - The interaction of Staphylococcus aureus, Yersinia enterocolitica, Y.
      pseudotuberculosis, Y. intermedia, Y. frederikseni, Y. kristenseni and
      erythrocytes was studied with the use scanning electron microscopy. Highly
      adhesive and moderately adhesive Staphylococcus and Yersinia strains displayed
      both individual coated bacterial cells and groups of cells interconnected by
      common intercellular matrix on the surface of erythrocytes. In nonadhesive
      Staphylococcus and Yersinia strains no coating was detected on the surface of
      bacterial cells. Some of Staphylococcus and Yersinia cells interacting with
      erythrocytes were at the stage of heteromorphism with different manifestations of
      L-transformation (cells with cell wall defects, spheroplasts and protoplasts).
      Heteromorphic cells did not adhere to the surface of erythrocytes.

PMID- 11949251
TI  - [Hospital acquired infections among newborns and parturients from radionuclide
      contaminated and control territories].
AB  - The comparative epidemiological study of hospital acquired infections (HAI)
      prevalence among newborns and parturient women in radionuclide contaminated
      territories (RT) and control territories (CT) was carried out. Observation
      covered altogether 2,837,471 newborns, of these 1,617,047 in CT, and 2,378,877
      parturient women, of these 1,352,831 in CT. A high level morbidity of thyroid
      gland diseases, diabetes mellitus, as well as puerperal sepsis and urogenital
      tract diseases, was detected among parturient women at RT. The specific feature
      of HAI among newborns in RT was high prevalence of hematological disturbances and
      hemolytic disease. Profound studies followed by specifically targeted programs
      and development of prophylactic measures should be carried out.

PMID- 11949252
TI  - [Effect of Azospirillum brasilense lectin on the kinetics of lymph nodes cell
      populations and cytokine status in experimental animals].
AB  - The complex study of the influence of A. brasilense Sp 7 lectin with carbohydrate
      specificity to L-fucose and D-galactose on the dynamics of cell populations in
      different structural functional zones of the white mice mesentery, as well as on
      the capacity of immunocompetent cells of mesenterial lymph nodes for synthesizing
      cytokines (interleukin-1, interleukin-6 and tumor necrosis factor), was carried
      out. A single oral administration of bacterial lectin in a dose of 4.5 micrograms
      produced a pronounced immunostimulating effect.

PMID- 11949253
TI  - [Lymphocyte subpopulations and level of the proinflammatory cytokines in the
      blood of patients with hepatitis C and with combined variant of hepatitis C and
      B].
AB  - Subpopulation of cytotoxic lymphocytes CD8 having both secretory and cytolytic
      antiviral activity is supposed to play the essential role in the virus
      elimination. Inflammatory reactions are also of importance in the hepatitis C
      pathogenesis, their intensity being regulated by anti-inflammatory cytokins. This
      study was aimed at determination of lymphocyte subpopulation indices--the
      relative content of cells carrying markers CD4, CD8, CD16, CD19, CD72, the
      parameters of the phagocytic activity of granulocytes and monocytes, as well as
      serum concentrations of anti-inflammatory cytokines IL-1, IL-6 and TNF-alpha.
      These indices were evaluated in a group 132 patients with confirmed hepatitis C
      or mixed hepatitis B + C diagnosis, depending on the disease form and markers of
      the infectious process activity (as determined in the PCR test for hepatitis C
      virus RNA) in comparison with a group of healthy donors. In patients with variant
      hepatitis under study a growth in anti-inflammatory mediators concentration was
      observed along with decreased indices of lymphocyte subpopulations responsible
      for cell-mediated immunity and the phagocytosis parameters. In the case of mixed
      hepatitis these differences were shown to be more manifested.

PMID- 11949254
TI  - [Clinical evaluation of the structural characteristics of peripheral blood
      leukocyte DNA in patients with viral hepatitis B].
AB  - The DNA structure of peripheral blood leukocytes in healthy donors and in viral
      hepatitis B patients was studied by the rate of the alkaline denaturation of DNA
      in cell lysates. An increased rate of the DNA alkaline denaturation of cell
      lysates was established, which was indicative of the damages in their DNA. The
      most pronounced damages of DNA were found in granulocytes of patients with highly
      active chronic hepatitis and hepatic cirrhosis, especially in cases of
      simultaneous delta-virus infection. The damage of leukocyte DNA reflected
      probably the accumulation of cells, committed to apoptosis, in peripheral blood.
      Apoptosis may be induced by cytotoxic lymphocytes recognizing HBV-infected cells.

PMID- 11949255
TI  - [Analysis of immune response of guinea pigs infected with Brucella melitensis].
AB  - The dynamics of the first antigen specific stage of immune response to Brucella
      infection was experimentally studied with the method of binding adsorbed
      antigenic immunoreagents with lymphocytes. The study revealed that the content of
      antigen-binding lymphocytes (ABL) reached its maximum as early as on day 7 after
      infection, gradually decreasing afterwards (but even on day 90 ABL could be
      detected in the blood). The specificity of ABL was proved by the fact that they
      were absent in noninfected animals, while in the animals infected with Brucella
      their content was higher than that of ABL specific to Yersinia enterocolitica O9;
      Brucella-specific ABL bound Brucella lipopolysaccharide (LPS) more intensively
      than Yersinia LPS. The detection of Brucella-specific ABL was inhibited by
      Brucella LPS more actively than by Yersinia LPS. The evaluation of the affinity
      of ABL to homologous LPS, made by the ratio of binding immunoreagents of the same
      specificity, but with suboptimal and optimal specificity, proved that an increase
      in the avidity of ABL occurred in the dynamics of the infectious process, which
      corresponded to the increase of their specificity.

PMID- 11949257
TI  - [Intestinal microflora and concomitant gastrointestinal diseases in patients with
      chronic hepatitis B and C].
AB  - In chronic viral hepatitis B and C the development of intestinal dysbacteriosis
      and high occurrence of concomitant diseases of the gastrointestinal tract were
      observed. In cases of increased dysbacteriosis degree and in the presence of
      concomitant diseases the blood plasma of patients exhibited higher activity in
      reaction with the of amebocytes lysate obtained from crabs of the genus Limulus.
      A suggestion was made that the endotoxin of Gram negative intestinal microflora
      could probably play some role in the development of pathological processes in
      chronic viral hepatitis B and C.

PMID- 11949256
TI  - [Effect of modified low density lipoproteins on humoral immune response and
      functional activity of macrophages in mice].
AB  - Intravenous injection of acetylated low density lipoproteins (acLDL) in mice in a
      dose of 0.5 mg per mouse decreased the intensity of humoral immune response to
      sheep red blood cells (SRBC) by 35%. The addition of acLDL to mouse peritoneal
      macrophages in vitro resulted in inhibition of Fc-dependent phagocytosis of SRBC
      and fourfold increased secretion of prostaglandins E2 by macrophages. Fc
      dependent phagocytosis of SRBC was also found to be inhibited by oxysterols (25
      hydroxycholesterol and 7-ketocholesterol), added to the incubation medium of
      macrophages in vitro in doses of 0.5-5 mg/ml. The conclusion was made that
      oxidative metabolism of cholesterol and arachidonic acid, contained in LDL, may
      mediate the immunomodulating effects of modified LDL.

PMID- 11949258
TI  - [State of normal intestinal microflora in preschool children living in the
      ecologically adverse region].
AB  - In children living in an ecologically unfavorable area the quantitative content
      of bifidobacteria and enterococci appeared to be considerably decreased while the
      level of sulfate-reducing clostridia, on the contrary, elevated. The suppression
      of bifidoflora leads to decreased immune responsiveness that promotes different
      somatic diseases. Bronchitis, pneumonia, tonsillitis, pharyngitis, otitis,
      allergic diseases, diseases of digestive organs, acute respiratory virus
      infections are more often registered in children living in ecologically
      unfavorable Central district than in children living in the ecologically
      favorable Lenin district.

PMID- 11949259
TI  - [Use of lactusan for the correction of microecological intestinal disturbances in
      children].
AB  - The study demonstrated that lactusan (lactulose) could be used as an effective
      remedy in dysbacteriosis. Twenty four sick children aged 1 month to 15 years were
      examined. Administration of lactusan to 21 patients resulted in perceptible
      improvement of clinical symptoms, mainly to the cessation of diarrhea. In 14
      children an increase in the population level of bifidobacteria and lactic acid
      bacteria and a decrease in the number of opportunistic microorganisms were
      observed. Lactulose should be referred to prebiotics.

PMID- 11949260
TI  - [Biological properties of clinical isolates of Mycobacterium tuberculosis].
AB  - The invasiveness of 2 grud sensitive and 8 holy-resistant M. tuberculosis
      clinical isolated was evaluated in experiments on BALB/c mice. Mycobacterial
      suspension was injected into the caudal vein of experimental animals. The results
      were evaluated by the degree of contamination of lungs and spleen of infected
      animals euthanized at different periods on time. The study revealed high
      variability in the degree of contamination of the organs of the animals infected
      with M. tuberculosis drug-resistant clinical isolates.

PMID- 11949261
TI  - [Etiology and structure of infectious complications of cytostatic therapy in
      children with acute lymphoblastic leukemia and non-B-cell non-Hodgkin lymphomas].
AB  - A retrospective analysis of medical histories with acute lymphoblast leucosis and
      non-B-cell non-Hodgkin lymphomas made it possible to reveal infectious
      complications of cytostatic therapy in 100% of children, namely: sepsis (0.3%),
      unidentified infection (12%), local infection (87.7%). Infectious complications
      of the cytopenic nature were localized mainly in the upper sections of the
      gastrointestinal tract and in upper respiratory tract. Bacterial infectious
      complications caused by opportunistic microorganisms with the prevalence of Gram
      positive flora, resistant to cephalosporins of generations I and II, occurred
      most frequently.

PMID- 11949262
TI  - [Estimation of diagnostic value of the microtest systems for biochemical
      identification of vibrios groups and their typing according to Heiberg's method].
AB  - Diagnostic value determination of microtest systems for biochemical
      identification of vibrios and their groups identification according to Heiberg's
      was made with the use of 260 collection strains of V. cholerae O1 and non-O1, as
      well as microorganisms belonging to other genera and families. The newly
      developed microtest systems were found to have a number of advantages over the
      traditional test tube method being more economic, ensuring rapid identification,
      standard and reproducible results.

PMID- 11949263
TI  - [Antilysozyme activity and antibiotic resistance of periulcerous zone microflora
      in patients with gastric and duodenal ulcer].
AB  - Antilysozyme activity (ALA) as well as antibiotic resistance were detected in 133
      microbial cultures isolated from bioptic specimens of the mucous membrane of the
      ulcerous and periulcerous zones, taken from patients with gastric and duodenal
      ulcer. In 85.7-94.7% of cases Gram positive cocci and in 62.5% of cases Gram
      positive bacilli showed no ALA. 50% of Gram negative bacteria cultures lacked
      ALA, while the remaining 50% exhibited this activity, on the average, 2.36 +/-
      1.40 mkg/ml. Lysozyme activity was determined in 33.3% of the isolated
      staphylococci strains both with and without ALA. Staphylococci isolated from the
      gastric mucosa of healthy controls had no ALA in 33.3% of cases, and in 66.7% of
      cases ALA was equal to 2 mkg/ml. Gram positive coccal microflora showed, mainly,
      high sensitivity to antibiotics. In Gram negative bacteria antibiotic resistance
      was determined in 44.3 +/- 21.2% of the isolates. In Gram negative microorganisms
      correlation between ALA and antibiotic resistance was observed. From the
      periulcerous zone of patients with gastric and duodenal ulcer persistence
      associated Gram negative microorganisms were mainly isolated.

PMID- 11949264
TI  - [Role of sialic acids in the immune response formation in tick-borne
      encephalitis].
AB  - The content of individual forms of sialic acids and total sialic acids in the
      lymphocytes of tick-borne encephalitis patients has been studied. The level of
      sialic acids has been found to depend on the clinical form of the disease and on
      the content of specific IgM and IgG to tick-borne encephalitis virus. Similar
      dependence has been established with respect to total sialic acids in
      lymphocytes.

PMID- 11949265
TI  - [Conjugative plasmids of Salmonella strains resistant to antibiotics].
AB  - Plasmid DNA profile and conjugative R-plasmids were detected in Salmonella
      clinical isolates. The study revealed that drug resistance of Salmonella clinical
      strains of different serovars was determined by R-plasmids with a mol. wt. of 60
      90 kD, carrying a certain spectrum of resistance to antibiotics. 9 types of
      conjugative plasmids, differing in their mol. wt. and resistance markers, were
      detected.

PMID- 11949266
TI  - [Phenomenon of apoptosis in the survival of enterobacteria in the parasite-host
      system].
AB  - Data on the apoptosis phenomenon with enterobacteria used as a model are
      presented. One of the mechanisms regulating the vital activity of eukaryotic
      cells is, together with cell proliferation and differentiation, the phenomenon
      known as "apoptosis". This physiological process of the eukaryotic cells death is
      used by many parasites in parasite--host relationships in different epitopes. The
      system known to trigger programmed cell death, is the surface receptor Fas, the
      receptor of tumor necrosis factor (TNF alpha) activated by the corresponding FasL
      ligand and TNF alpha, which further triggers the cascade mechanisms of the
      execution program. In various representatives of enterobateria different proteins
      serve as Fas ligand, viz. protein IpaB in Shigella flexneri, SipB activating
      converting enzyme IL-1 beta, identical to capsase-1, in Salmonella spp., YopP in
      Yersinia spp. Still the mechanism triggering apoptosis in Yersinia spp. has some
      original features. In Escherichia coli alpha-hemolysin is the factor triggering
      the suicidal program, the triggering mechanism being mediated by an increase in
      intracellular calcium ions.

PMID- 11949267
TI  - [Secreted pathogenicity factors of enterobacteria].
AB  - Data on the secreted pathogenicity factors of different enterobacterial species
      are reviewed. Update information on toxin classification is presented. The main
      cytotoxic and cytotonic enterotoxins, transient pore forming toxins (RTX),
      cytotoxic necrotizing factor and injection toxins have been analyzed. Problems
      connected with the mechanism of action and genetic control of known
      enterobacterial toxins are discussed.

PMID- 11949268
TI  - [Viral haemorrhagic fevers--evolution of the epidemic potential].
AB  - In this review modern data on dangerous and particularly dangerous viral
      haemorrhagic fevers caused by a group of viruses belonging to the families of
      phylo-, arena-, flavi-, bunya- and togaviruses are presented. Morbidity rates and
      epidemics caused by Marburg virus, Ebola fever virus, Lassa fever virus,
      Argentinian and Bolivian haemorrhagic fever viruses, dengue haemorrhagic fever
      virus, Crimean haemorrhagic fever virus, Hantaviruses are analyzed. Mechanisms of
      the evolution of the epidemic manifestation of these infections are considered.
      The importance of the development of tools and methods of diagnosis, rapid
      prevention and treatment of exotic haemorrhagic fevers is emphasized.

PMID- 11949269
TI  - [Results of basic and applied investigations on oral immunization against
      smallpox ].
AB  - The results of fundamental and applied investigations on the development and
      trial of the oral administration of smallpox vaccine and live recombinant
      smallpox-hepatitis vaccine (Revax VT) in tablets are summarized. In comparative
      experiments on animals (rabbits, monkeys and guinea pigs) and human immunization
      the oral smallpox vaccine in tablets was shown to ensure equal effectiveness and
      greater safety in comparison with traditional smallpox vaccine for skin
      application. The study confirmed the natural and physiological character of oral
      immunization as a result of direct contact of immunogen with the mucous membrane
      of the digestive tract--an essential immunocompetent organ of the lymphoid
      system. The conclusion was made that oral immunization was the safe and most
      promising method of immunization against smallpox under modern conditions.

PMID- 11949270
TI  - The thyroid gland: physiology and pathophysiology.
AB  - The thyroid gland contains many follicular cells that store the thyroid hormones
      within the thyroglobulin molecule until they are needed by the body. The thyroid
      hormones, often referred to as the major metabolic hormones, affect virtually
      every cell in the body. Synthesis and secretion of the thyroid hormones depend on
      the presence of iodine and tyrosine as well as maturation of the hypothalamic
      pituitary-thyroid system. Interruption of this development, as occurs with
      premature delivery, results in inadequate production of thyroid-stimulating
      hormone and thyroxine, leading to a variety of physiologic conditions. Pathologic
      conditions occur in the presence of insufficient thyroid production or a defect
      in the thyroid gland. Laboratory tests are important in diagnosing conditions of
      the thyroid gland. A thorough history in combination with clinical manifestations
      and radiologic findings are also useful in diagnosing specific thyroid
      conditions. Nurses play an important role in identifying and managing thyroid
      disorders and in providing supportive care to infants and their families.

PMID- 11949271
TI  - The use of inhaled glucocorticosteroids and recovery from adrenal suppression
      after systemic steroid use in a VLBW premature infant with BPD: case report and
      literature discussion.
AB  - Despite development of many prevention and treatment modalities for
      bronchopulmonary dysplasia (BPD), a form of chronic respiratory insufficiency in
      premature infants recovering from respiratory distress syndrome, BPD remains a
      treatment challenge and a significant cause of long-term morbidity. A ventilator
      dependent very low birth weight infant in our newborn special care unit was
      receiving multiple courses of systemic dexamethasone for severe respiratory
      failure. The infant demonstrated adrenal suppression manifested by a baseline
      cortisol concentration below reported levels in infants of similar birth weight
      and postnatal age. We hypothesized that he had developed adrenal insufficiency as
      a result of the prolonged systemic steroid administration used to treat his
      respiratory problems. We further hypothesized that inhaled beclomethasone therapy
      would aid in the infant's recovery phase during relative adrenal insufficiency-
      and so substituted inhaled for systemic steroids. Inhaled corticosteroid
      treatment improved the clinical respiratory course and postnatal growth of this
      premature infant with BPD without inhibiting his recovery from adrenal
      insufficiency.

PMID- 11949272
TI  - Theophylline or caffeine: which is best for apnea of prematurity?
AB  - Apnea of prematurity is a common problem of the premature infant under 30 weeks
      gestation. Theophylline and caffeine, two methylxanthines, are widely used to
      treat this condition. The drugs are equally effective in preventing apnea in the
      premature infant. Caffeine citrate has many advantages over theophylline,
      however, including once-a-day dosing, more predictable plasma concentrations,
      earlier onset of action, and minimal side effects. Caffeine is therefore the
      initial drug of choice for apnea of prematurity.

PMID- 11949273
TI  - How rewarding can a pacifier be? A systematic review of nonnutritive sucking in
      preterm infants.
AB  - PURPOSE: To determine whether nonnutritive sucking (NNS) in preterm infants
      influences selected outcome variables. DESIGN: A systematic review, based on the
      Cochrane Collaboration format, of trials utilizing experimental or quasi
      experimental designs in which NNS (by pacifier) was compared to no provision of
      NNS; related to naso/orogastric tube feedings, bottle feedings, or not associated
      with feeding. SAMPLE: All infants born at < 37 weeks gestation. This review
      consisted of 19 studies; 13 were randomized controlled trials. Sample sizes
      ranged from 10 to 59 infants and totaled 518 infants. MAIN OUTCOME VARIABLE:
      Weight gain, energy intake, heart rate, oxygen saturation, length of hospital
      stay, intestinal transit time, and postconceptional age at full oral feedings.
      RESULTS: NNS significantly decreased the length of hospital stay in preterm
      infants. The review did not reveal a consistent benefit of NNS with respect to
      other major clinical variables. No negative outcomes were reported in any of the
      studies.

PMID- 11949274
TI  - Introduction to the revised Neonatal Resuscitation Program guidelines: questions
      and answers to get you started.
AB  - In October, 2000, the American Academy of Pediatrics (AAP) and the American Heart
      Association (AHA) introduced revised guidelines for the Neonatal Resuscitation
      Program (NRP). These revisions affect the practice of neonatal resuscitation as
      well as the administrative components of the program. This article cannot address
      every program revision, but introduces the reader to how program changes
      occurred, guideline revisions that affect practice, and changes in NRP
      educational tools and resources.

PMID- 11949275
TI  - Supporting parents in the NICU: guidelines for promoting parent confidence and
      competence.

PMID- 11949276
TI  - Lorazepam.
AB  - The nurse administering any BZD--especially lorazepam--to a neonate must be
      knowledgeable about the drug's effects and risks and must remember that BZDs do
      not provide analgesia. The sedative effects of lorazepam will increase with
      concomitant use of opioids. The nurse must be alert for adverse reactions (Table
      1). Close monitoring of the neonate's respiratory effort and blood pressure is
      important. Because of the various reported cases of myoclonus in neonates after
      lorazepam administration, close observation for seizure activity is imperative.
      Although lorazepam use may be beneficial in specific instances, administration
      should be approached with caution in the neonate (especially in the preterm
      neonate) and other agents considered.

PMID- 11949277
TI  - An open letter to members and chapter affiliates concerning the current state of
      affairs of our parent organization, the National Association of Neonatal Nurses
      (NANN).

PMID- 11949278
TI  - The collapse of the National Association of Neonatal Nurses.

PMID- 11949279
TI  - Time for change ... relationships between nursing and medicine.

PMID- 11949280
TI  - Update: TDH implements improved bloodborne pathogen laws.

PMID- 11949281
TI  - Seeking magnet hospital status. A TNA member's account of the arduous application
      process.

PMID- 11949283
TI  - A model for facilitation of critical reflective practice: Part I--Introductory
      discussion and explanation of the phases followed to construct the model.
AB  - The purpose of this inquiry was to construct a model for facilitation of critical
      reflective practice, based on thorough analysis of the main concepts (critical
      thinking and reflection), related viewpoints, models and theories; and the data
      gathered and analyzed during, the naturalistic inquiry. The constructed model
      evolved from empirical observations, intuitive insights of the inquirer and from
      deductions combining ideas from several fields of inquiry. The model for
      facilitation of critical reflective practice postualates that practitioners have
      the inherent potential to change from auto-pilot practice to critical reflective
      practice. The purpose of the model is the facilitation of heightened awareness of
      the self, to enable health care professionals to consciously meet community needs
      and expectations. The desired outcome is transformative intellectuals who will
      strive to empower others to become critical reflective learners and practitioners
      themselves. The process followed during the construction of the model and the
      constructed model will be discussed in three (3) articles, namely: A model for
      facilitation of critical reflective practice: Part I--Introductory discussion and
      explanation of the phases followed to construct the model. A model for
      facilitation of critical reflective practice: Part II--Conceptual analysis within
      the context of constructing the model. A model for facilitation of critical
      reflective practice: Part III--Description of the model.

PMID- 11949282
TI  - Assessment of learning needs and the development of an educational programme for
      registered nurses in advanced midwifery and neonatology.
AB  - A key step in the development of any educational programme is learning needs
      assessment. This is however often neglected. The purpose of this research was to
      identify learning needs of potential students in order to develop a relevant
      educational programme for registered nurses in advanced midwifery and
      neonatology. A survey design was used, and the population of the study was the
      registered nurses in the Free State. Two thousand questionnaires were mailed to
      respondents, selected by means of simple random sampling. Advanced educational
      programmes emphasize the teaching of advanced knowledge and skills and accept
      that the students entering these programmes already have specific knowledge and
      skills included in the curricula for basic programmes. This is contrary to the
      findings of this study. The results underline the importance of learning needs
      assessment in the development of relevant educational programmes.

PMID- 11949284
TI  - A model for facilitation of critical reflective practice: Part II--Conceptual
      analysis within the context of constructing the model.

PMID- 11949285
TI  - A model for facilitation of critical reflective practice: Part III--Description
      of the model.

PMID- 11949287
TI  - Distance education doctoral program for nurses as offered by the University of
      South Africa (UNISA).

PMID- 11949286
TI  - Perceptions of sexually transmitted diseases among teenagers.
AB  - An exploratory descriptive study was undertaken, focussing on sexually
      transmitted diseases (STD) among teenagers. The aim of the study was to explore
      and describe the possible reasons for the high rate of sexually transmitted
      diseases in teenagers. The perceptions of teenagers and community nurses
      regarding sexually transmitted disease among teenagers involved in the teenage
      clinic in a specific predominantly black area were assessed. Twenty teenagers and
      five community nurses were participants in the study. Two focus group interviews
      were conducted with teenagers and community nurses. It can be concluded that the
      attitudes of community nurses may have an influence on the high rate of sexually
      transmitted diseases among teenagers. The knowledge of the teenagers about
      sexually transmitted diseases is often based on myths and misconceptions which
      could be intensified by the community nurse. The recommendations made are that
      the education standards of all community nurses should be reviewed and adapted to
      meet the needs of teenagers attending the teenage health services. The policy on
      in-service training must be reviewed and monitored. Community nurses' intensive
      training on teenage health service delivery and sexually transmitted diseases
      services should be in accordance with the principles of Primary Health Care.
      Community nurses need to attend intensive courses on interpersonal skills
      specifically related to teenagers. Selection procedures for recruiting community
      nurses to attend to teenagers specifically should be researched. Teenagers should
      be involved in planning programs and the teenage clinic should be evaluated
      frequently to improve the standards. The availability of adequate teenage health
      services can result in a decrease in sexually transmitted diseases among
      teenagers.

PMID- 11949289
TI  - Risk for traumatization among violent crime victims in an urban community sample
      in South Africa.
AB  - This study intended to investigate risk factors for the development of trauma
      symptoms as a consequence of violent crime in an urban South African community.
      The sample included 128 adult victims of violent crime chosen by snowball
      sampling. The adults were 36 (28.1%) males and 92 females (71.9%) in the age
      range of 18 to 52 years (M age 36.6 yr., SD = 8.9). Results indicate that the
      most common violent crimes experienced among the participants were rape
      (attempted rape), followed by physical assault, armed robbery, attempted murder
      and threat in that order. The majority of the victims scored high on the Kolner
      Risk Index (for traumatization)--several case examples are given. Analysis of
      Variance indicated that almost all factors of the Kolner Risk Index seem to be
      significantly correlated with PTSD outcome measures (PTSS-10, IES-R,
      Peritraumatic Dissociation and Trauma Belief). It is concluded that the Kolner
      Risk Index can be a useful tool for identifying crime victims at risk for the
      development of trauma symptoms, especially in (mental) health care settings.

PMID- 11949288
TI  - Exploring the trauma care nurse's lived experiences of dealing with the violent
      death of their clients.
AB  - A phenomenological approach was used to explore the phenomenon, violent death,
      from the perspective of trauma care nurses working in Kwa-Zulu Natal. Three
      relatively unstructured interviews were undertaken on an individual basis with
      each lasting thirty to forty-five minutes long. The researchers applied the
      principle of theoretical saturation and a total of seven participants from three
      level-one trauma units were included in the study. All the interviews were tape
      recorded and transcribed, and manual analysis, as well as a qualitative software
      package--NUD*IST--was used to identify experiential themes within the data. The
      trauma care nurses conceptualized violent death as being sudden, unpredictable,
      senseless and not as dignified or peaceful as a non-violent death. A number of
      issues that made confronting violent death difficult were raised and the trauma
      care nurses described a number of emotional and physical reactions that they
      experienced due to exposure to these situations. A number of recommendations were
      suggested for the trauma care nurses, nursing management, nurse educators and for
      future research in an attempt to prevent the loss of these valuable nurses from
      the nursing profession.

PMID- 11949290
TI  - Problems encountered by BA Cur graduates and recommendations for enhancing
      learner support.
AB  - Distance education is becoming ever more important in providing continuing post
      basic, and especially postgraduate, education to practising professional persons,
      including nurses. As more and more institutions in the Republic of South Africa
      offer distance education courses to nurses, it is essential to take note of the
      positive and negative experiences of successful graduates of these programmes, in
      order to enhance the learning opportunities, and the success rate of nurses
      pursuing such distance education courses. A brief historical overview is provided
      about the University of South Africa (Unisa) and about the Department of Advanced
      Nursing Sciences at this distance education university. This background
      information should assist the reader in contextualising the research findings.
      Questionnaires were posted to all Unisa's 1998 BA Cur graduates. The research
      report focuses on the 1998 BA Cur (nursing) graduates' biographic data, their
      experiences of pursuing distance education post basic nursing courses, their
      positive and negative perceptions of these experiences and their recommendations
      for enhancing other students' success.

PMID- 11949291
TI  - Integration of the primary health care approach into a community nursing science
      curriculum.
AB  - The purpose of this article is to explore and describe guidelines for integration
      of the primary health care approach into a Community Nursing Science Curriculum
      in a Nursing College in Gauteng. A qualitative, exploratory, descriptive and
      contextual research design was utilized. The focus group interviews were
      conducted with community nurses and nurse educators as respondents. Data were
      analysed by a qualitative descriptive method of analysis as described in Creswell
      (1994: 155). Respondents in both groups held similar perceptions regarding
      integration of primary health care approach into a Community Nursing Science
      Curriculum. Five categories, which are in line with the curriculum cycle, were
      identified as follows: situation analysis, selection and organisation of
      objectives/goals, content, teaching methods and evaluation. Guidelines and
      recommendations for the integration of the primary health care approach into a
      Community Nursing Science Curriculum were described.

PMID- 11949292
TI  - A "Youth Multi-function Centre" in the Free State: an alternative to clinic-based
      HIV/AIDS prevention and care.
AB  - The youth are especially vulnerable to the HIV/AIDS epidemic in South Africa. In
      the Free State (second highest incidence of HIV/AIDS among the provinces), the
      Welkom-Goldfields area may for various reasons be singled out as a high risk area
      for HIV/AIDS which should receive priority attention in attempts to combat the
      disease. It is suggested that a Youth Multi-function Centre would place youth
      reproductive health care in the broader development and life skills arena--where
      it could be thought to rightfully belong. The objectives of the paper are to
      depict the rationale for a Youth Multi-function Centre, to broadly conceptualise
      a Youth Multi-function Centre, and to report on the process and methodology
      followed in an attempt to actually establish such a centre in Thabong/Welkom.

PMID- 11949293
TI  - Transformation management of primary health care services in two selected local
      authorities in Gauteng.
AB  - The transformation of health services in South Africa today is governed by the
      political, policy and legislative frameworks. This article focuses on the
      transformation of a primary health care service within a local authority in
      Gauteng. The purpose with this article is to explore and describe the perceptions
      (expectations and fears) of selected managers employed in this primary health
      care service. The results are utilised to compile a strategy (framework) for
      transformation management and leadership within the primary health care service.
      A qualitative research design was utilised and the data was collected by means of
      individual interviews with selected managers in the service, followed by a
      content analysis. The expectations and fears of managers focus mainly on
      personnel matters, community participation/satisfaction, salaries and parity,
      inadequate stocks/supplies and medication, the deterioration of quality service
      delivery and the need for training and empowerment. These results are divided
      into structure, process and outcome dimensions and are embodied in the conceptual
      framework for the transformation and leadership strategy. It is recommended that
      standards for transformation management be formulated and that the quality of
      transformation management be evaluated accordingly.

PMID- 11949294
TI  - [Perceptions of nursing service managers in the South African Military Health
      Service on their level of motivation].
AB  - The process of transformation in the South African Military Health Services, has
      influenced the nursing service managers' level of motivation and the following
      research question is applicable: what are the perceptions of the nursing service
      managers within the South African Military Health Services on their level of
      motivation? The purpose with this study was to explore and describe the
      perceptions of nursing service managers on their level of motivation within these
      health services. A qualitative research design was utilized and four focus group
      interviews were conducted with 33 nursing service managers country wide. The
      transcribed interviews were exposed to a content analysis. The results confirm
      that the level of motivation amongst these nursing service managers is low. The
      demotivators relate mainly to the following: inadequate acknowledgement, job
      insecurity in relation to the future, problems with the process of integration,
      transformation and rationalization, problems with management, many labour related
      issues, poor/inadequate communication, inadequate support, increased work load,
      poor physical environment, negative publicity and poor self motivation. Although
      there were a few motivators identified, they were of less importance. These
      results were interpreted within Herzberg's motivation theory to identify the
      hygiene/maintenance factors and to assess whether the important motivators were
      in place. During any process of change, and/or when the level of motivation
      amongst employees is low, it is important to adequately manage the environment
      (hygiene/maintenance factors within the Herzberg theory). But it is even more
      important to ensure that the motivators are in place or to intensify them. It is
      therefore recommended that a motivation strategy, based on the Herzberg theory as
      well as the Hackman-Oldham job enrichment model, be developed, implemented and
      evaluated.

PMID- 11949295
TI  - Maintaining compliance at home: helping the elderly with their medications.
AB  - The elderly population consumes more drugs for their chronic conditions compared
      to any age group. In this study it was indicated that the average elderly takes
      two to four drugs per day. The high quantity and wide range of drugs used by the
      elderly can lead to significant risks. Adding to the risks is the problem of
      compliance. Areas of concern regarding safety in administering medications to the
      elderly are the need for increased awareness of the effects of drugs in their
      systems.

PMID- 11949296
TI  - The reliability and validity of self-reported reproductive history and obstetric
      morbidity amongst Birth to Ten mothers in Soweto.
AB  - OBJECTIVE: To assess whether self-reports of reproductive history and obstetric
      morbidity provide an accurate basis for clinical decision-making. SETTING,
      PARTICIPANTS AND METHODS: Self-reports of maternal age and reproductive history,
      together with clinical measurements of five medical disorders, were abstracted
      from the obstetric notes of 517 mothers whose children were enrolled in the Birth
      to Ten study. These data were compared to self-reported information collected by
      interview during the Birth to Ten study. FINDINGS: The reliability of self
      reported age and gravidity was high (R = 0.810-0.993), yet self-reports of
      previous miscarriages, terminations, premature- and stillbirths were only fairly
      reliable (Kappa = 0.48-0.50). Self-reported diabetes and high blood pressure had
      specificities of more than 95% for glycosuria, hypertension and pre-eclampsia.
      However, the specificity of self-reported oedema for hypertensive disorders and
      the specificity of self-reported urinary tract infection for STD seropositivity
      were only around 65%. CONCLUSIONS: The modest reliability and limited validity of
      self-reported obstetric morbidity undermines the clinical utility of this
      information. RECOMMENDATIONS: These results strengthen the case for providing
      mothers with "Home-based Maternal Records" to facilitate access to accurate
      obstetric information during subsequent clinical consultations.

PMID- 11949297
TI  - [Guidelines for implementation of tuberculosis education-learning].
AB  - This article is a follow up article of the previously published article "Die
      belewenis van die pasient en die verpleegkundige tydens tuberkulose-onderrig" and
      focuses on guidelines formulated on the basis of the research findings. These
      guidelines have been formulated in order to promote the nurse's knowledge and
      skills concerning: interpersonal relations, subject knowledge, a task versus
      patient orientated nursing approach, the motivation of the nurse, social support
      systems, stimulation of the patient's motivation, recovery from the patient's
      chest centredness and the acceptance of responsibility for his own health as well
      as the affirmation of the role of the nurse.

PMID- 11949298
TI  - Facilitation skills for nurses.
AB  - Using the person-centered approach, facilitation in this study was conceptualised
      as providing opportunities for personal growth in the patient, and
      operationalised in a skills workshop for 40 nurses from different hospitals in
      Gauteng. The first objective was to evaluate the workshop and the second to
      ascertain its effect on the participant's experienced performance. A combined
      quantitative and qualitative research design was used. The quantitative
      measurement (Personal Orientation Inventory, Carkhuff scales) indicated that the
      workshop stimulated self-actualisation in terms of intrapersonal awareness, and
      the interpersonal skills of respect, realness, concreteness, empathy, as well as
      in terms of attending and responding behaviour. The qualitative measurement (a
      semi-structured interview) indicated that the participants were able to empower
      patients to find their own answers to difficult personal questions. The
      alternative hypothesis was accepted, namely that this workshop in facilitations
      skills significantly enhanced the intra- and interpersonal characteristics
      associated with self-actualisation and the facilitation of growth in patients.
      The findings highlighted the difference between the two roles of instructor and
      facilitator, and recommendations to this effect were formulated.

PMID- 11949300
TI  - Standards of care and tissue viability.

PMID- 11949299
TI  - The utilization of a Midwifery Obstetrical Unit (MOU) in a Metropolitan area.
AB  - In this study an explorative, descriptive design which is contextual in nature,
      is utilized. The objective of the study is three-fold: Firstly, to describe the
      opinions of members of the community about the reasons for the under-utilization
      of the Midwifery Obstetrical Unit (MOU); secondly, to describe the suggestions of
      the community for improving the utilization of the MOU and thirdly, to describe
      intervention strategies for community nurses to improve the utilization of the
      MOU. Data was collected by means of focus group interviews, and was analysed
      using Tesch's (in Cresswell, 1994: 154-155) method of data analysis.
      Trustworthiness was ensured by using the method of Guba and Lincoln (1985). The
      respondents were mothers who delivered their babies at the hospital, mothers who
      delivered their babies at the MOU, members of the Community Health Committee and
      MOU nurses. Data was collected in two phases. Phase I dealt with the first
      question: What is your opinion about the reasons for the under-utilization of the
      MOU? Phase II dealt with the second question: What are your suggestions for
      improving the utilization of the MOU? The four groups participated in Phase I as
      well as in Phase II, the reason being to involve the groups in identifying
      problems and finding solutions with which they would be comfortable, since it
      would be their ideas. This whole exercise was, however, carried out in line with
      the RDP principle of people driven approach or community involvement. The
      investigation revealed that the community was not utilizing the MOU because of
      the following reasons: Negative attitudes of nurses. Lack of material and human
      resources. Poor safety and security measures. Lack of community
      involvement/participation. The focus groups then identified the following
      suggestions for improving the utilization of the MOU: Change of attitudes by
      nurses towards the patients. Availability of material and human resources. Proper
      safety and security measures in the MOU. Community involvement/participation.
      Integration of health services. Intervention strategies for community nurses to
      improve the utilization of the MOU were based on the literature as well as the
      suggestions made by the focus group respondents because the researcher found the
      suggestions to be realistic.

PMID- 11949301
TI  - Case study to illustrate a multidisciplinary approach to a case of critical limb
      ischaemia and the role of chemical lumbar sympathectomy.
AB  - This case study illustrates the role of the Podiatrist in the primary health care
      team and how a multidisciplinary approach to treatment promotes successful
      diagnosis and treatment regimes. It also outlines the role for chemical lumbar
      sympathectomies in treating critical lower limb ischaemia, a procedure regarded
      as having been superseded by more effective treatments but which proved to be the
      treatment of choice in this case. The subject of this case study presented at a
      community podiatry clinic exhibiting the signs of acute ischaemia, together with
      two recently developed ulcers on her right foot. After further vascular
      investigations, including angiograms and doppler studies, a blockage in the
      popliteal artery was revealed. Due to anatomically slender arteries, angioplasty
      and by-pass surgery were contra indicated. A chemical lumbar sympathectomy was
      performed in an attempt to increase blood flow to the tissues and to reduce the
      extreme pain being experienced by the patient. This proved successful, allowing
      the lesions to heal and also the collateral circulation to develop, resulting in
      a re-vascularized, viable foot.

PMID- 11949302
TI  - Developing clinical guidelines: issues and challenges.
AB  - Clinical guidelines are viewed as an important tool in the quest to promote
      evidence based practice. Consequently, there has been a proliferation in
      guideline development at a national and local level. This paper describes what
      clinical guidelines are and how they have been developed by a national
      organisation--the Royal College of Nursing (RCN). Drawing on the development of
      two tissue viability guidelines: The Management of Patients with Venous Leg
      Ulcers and Risk Assessment and Prevention of Pressure Ulcers, some challenges
      inherent in guideline development are outlined. Certain desirable attributes that
      a clinical guideline should exhibit in order for it to be utilisable and
      effective in practice are outlined as these provide a standard for guideline
      developers. In reality the practice of guideline development will depend upon the
      topic, the experience of the guideline group, the purpose of the guidelines and
      the evidence available. Our experience suggests that producing a clinically valid
      and utilisable guideline is a labour and resource intensive process. It is also
      time consuming. An alternative strategy to developing local guidelines from
      scratch would be to adapt an existing guideline to local circumstances. A
      stepwise process is presented in the paper to assist people with this process.

PMID- 11949303
TI  - Case study methodology in tissue viability. Part 1: Methodological
      considerations.
AB  - Case studies are often presented in relation to tissue viability problems. Within
      hierarchies of evidence, case studies are sometimes seen to be on a par with
      expert opinion. This paper examines the case study as a research method and seeks
      to determine its value in tissue viability research. The term 'case study'
      denotes a general strategy for research where several methods of data collection
      are used to provide an in-depth analysis of an individual, group or institution.
      Three types of case study are used in research: intrinsic, instrumental and
      collective. All case studies utilize data triangulation within their design, that
      is, the use of a variety of sources of data within a study. It is one of the
      major strengths of the case study method. Data sources include documentary data
      sources, observation and interviews. As in any research, validity and reliability
      are important in case study methodology; in particular, construct validity,
      internal validity and external validity. Case studies are potentially vulnerable
      to observer error and observer bias. Examples are given of potential case studies
      in tissue viability and their strengths and weaknesses. If undertaken
      prospectively, with clearly defined multiple sources of data collection and a
      documented chain of evidence, case studies can add breadth to our knowledge and
      experience of caring for patients with tissue viability problems.

PMID- 11949304
TI  - Oral pentoxifylline for treatment of venous leg ulcers.

PMID- 11949305
TI  - A longitudinal, quality of life study comparing four layer bandaging and
      superficial venous surgery for the treatment of venous leg ulcers.
AB  - OBJECTIVE: To investigate and compare changes in quality of life of patients with
      venous ulcers undergoing treatment with either four layer bandaging or
      superficial venous surgery. DESIGN: Fifteen patients with venous ulcers were
      selected from two treatment groups--either four layer bandaging or superficial
      venous surgery. Each received a postal questionnaire at pretreatment, four weeks
      and twelve weeks post treatment. The EuroQol quality of life questionnaire was
      used along with a disease specific questionnaire devised by the author. Analysis
      of results was undertaken using validated statistical methods. SETTING:
      Department of Vascular Surgery Leicester Royal Infirmary and Fosse Health (NHS)
      Trust (now the Leicestershire and Rutland Healthcare NHS Trust). MAIN OUTCOME
      MEASURES: To measure changes in quality of life of patients undergoing
      superficial venous surgery or four layer bandaging. RESULTS: Treatment over the
      twelve week period resulted in improvements in quality of life for both treatment
      groups (P = 0.001 for surgery and P = 0.019 for bandaging). No statistical
      differences in quality of life between the two treatment modalities were found at
      four and twelve weeks. CONCLUSION: There was evidence of an improvement in
      quality of life for both groups following twelve weeks of treatment. Improvements
      in pain and general quality of life were more marked in the bandaging group.
      Systems of care that offer rapid improvement to the patient's quality of life and
      wellbeing must be considered when planning effective leg ulcer management.

PMID- 11949306
TI  - Research to inform the strategic management of supply in pressure area care.
AB  - The NHS spends an estimated 45 million Pounds each year on products and services
      directly relating to the prevention and management of pressure sores. The role of
      the NHS Purchasing and Supply Agency (one of two successor bodies to NHS
      Supplies) at the most fundamental level is to ensure that the NHS secures maximum
      value from that expenditure. However, the Agency is also expected to establish
      and implement an overall framework for the management of purchasing and supply in
      the NHS--and one that increasingly takes into account the key government themes
      of efficiency and quality of care. This paper is in two parts. Part A describes
      the rationale for a more strategic approach to the management of supply at the
      macro level, and illustrates how the broad principles are being applied to
      pressure area care. Part B outlines how qualitative research has been used to
      inform the development of a 'supply strategy' in this field, and discusses the
      main outputs of this study. The research found significant differences in trusts'
      approaches to pressure area care, depending on the type, size and specialty of
      trust and the experiences and views of individuals. The level and profile of
      expenditure on pressure relieving equipment was similarly diverse. Rental
      arrangements were favoured over capital purchase in most of the trusts visited,
      although many had a mixed economy. Common themes were continuity of care, the
      importance of prevention, value for money and the need for an holistic approach.

PMID- 11949307
TI  - Case study methodology in tissue viability. Part 2: A study to determine the
      levels of knowledge of nurses providing care for patients with leg ulcers in an
      acute hospital setting.
AB  - One of the main components of the clinical governance framework is a
      comprehensive programme of quality improvement activity that includes the
      implementation of evidence-based, everyday clinical practice. This paper
      addresses the challenges surrounding the implementation of one area of evidence
      based practice, the management of leg ulcers in an acute hospital trust. The aim
      of the study was to distinguish the levels of knowledge of nurses providing care
      for patients with leg ulcers within an acute hospital setting. The design used
      was that of a collective case study. Each 'case' was a patient with a leg ulcer
      and the nurses who cared for that patient. They were studied in order to provide
      insight into the nurses' understanding of leg ulcer management. A number of
      themes were identified as being common to all the cases. They are: evidence-based
      practice, nursing skills, quality of life, patient understanding of their ulcer
      and pain. Each of these themes identified areas of knowledge deficit in the
      nurses. As part of the implementation of a leg ulcer policy an education
      programme is being developed to address these deficits.

PMID- 11949308
TI  - Travel broadens the mind--you bet!

PMID- 11949309
TI  - Current issues in pressure ulcer management of bedfast elderly in Japan.

PMID- 11949310
TI  - The future of nutrition and wound healing.
AB  - Nutrition is vital to all bodily processes. During wound healing, it is essential
      that nutrients are available as they form the building blocks for tissue repair.
      Nutrition may therefore affect healing due to an overall deficiency of intake,
      either due to non-availability or due to inability of the patient to absorb
      sufficiently to meet their requirements. Alternatively, deficiencies of specific
      nutrients may also inhibit healing and on the converse some additives, not
      normally present in large quantity in the diet, may have beneficial effects. This
      review considers the nutritional factors affecting wound healing and some
      developments that may alter the future of therapy.

PMID- 11949311
TI  - Pressure ulcer education.

PMID- 11949313
TI  - [Screening of oral language disorders in children in child care].

PMID- 11949316
TI  - [Children and play, two inseparable terms....].

PMID- 11949317
TI  - [What role for play in the nursing relation?].

PMID- 11949318
TI  - [Play and nursing care, what incidences?].

PMID- 11949319
TI  - [The function of play in the psychomotor development of children].

PMID- 11949321
TI  - [Learning to communicate, a childhood play....].

PMID- 11949320
TI  - [Play and physical therapy in hospitalization].

PMID- 11949322
TI  - [How does the speech therapist play?].

PMID- 11949323
TI  - [Role of the pediatric psychiatrist at the hearing of young victims].

PMID- 11949325
TI  - [Management of pain in the multi-handicapped child].

PMID- 11949324
TI  - [A screening for weight....].

PMID- 11949326
TI  - [Pediatric nurses worry about their future. Interview by Celine Dekussche].

PMID- 11949327
TI  - [That the hospital should also be a cultural space....].

PMID- 11949328
TI  - [Seeds of violence].

PMID- 11949330
TI  - [Solutions to alleviate the lack of organ donors].

PMID- 11949331
TI  - [Report from the National Observatory on cystic fibrosis in France].

PMID- 11949332
TI  - [Contact eczema in children, topography and chronology of the lesions guides the
      investigation].

PMID- 11949334
TI  - [Lying, from an ethical point of view].

PMID- 11949336
TI  - [The lying child, culpable or victim?].

PMID- 11949335
TI  - [The "myth of lying", a process structuring the collective psychic life].

PMID- 11949337
TI  - [A little liar becomes a big one...especially if no one listens to him].

PMID- 11949339
TI  - [If adults don't have the right to lie, children do have the right. Interview by
      Catherine Maisonneuve].

PMID- 11949338
TI  - [Why tell the truth to parents?].

PMID- 11949340
TI  - [Food allergies, pay attention to peanuts!].

PMID- 11949341
TI  - [Management of postoperative pain in infants].

PMID- 11949342
TI  - [Discovery of the body].

PMID- 11949343
TI  - [Lifting and holding a baby].

PMID- 11949344
TI  - [Putting the infant to bed].

PMID- 11949345
TI  - [The reactivation of the pediatric nurse education program is happening].

PMID- 11949346
TI  - [After the Perruche decision, the ethics committee's counsel on congenital
      handicaps and their prejudices].

PMID- 11949347
TI  - Specialist nurses. Money well spent.

PMID- 11949348
TI  - Biological weapons. Germs of fear.

PMID- 11949349
TI  - Should newly qualified nurses be forced to work in the  NHS?

PMID- 11949350
TI  - Changing roles. The same, but different.

PMID- 11949351
TI  - Cross-cultural care. What are you afraid of?

PMID- 11949352
TI  - I'm going to a land down under.

PMID- 11949353
TI  - Time to put the R back in TPR.

PMID- 11949354
TI  - Introducing a medical emergency team.

PMID- 11949355
TI  - Client involvement is the sure way to better health.

PMID- 11949356
TI  - Detecting pain in people with profound learning disabilities.

PMID- 11949359
TI  - I am a nurse in theatre and would like to set up a practice development group.

PMID- 11949358
TI  - Teaching students in the clinical setting. Part Five.

PMID- 11949361
TI  - Waste disposal for the ostomate in the community.

PMID- 11949362
TI  - Fast-track toilet training.

PMID- 11949360
TI  - Cardiopulmonary resuscitation. Checking equipment.

PMID- 11949363
TI  - Bladder health and continence care.

PMID- 11949364
TI  - How foot and mouth disease affected a rural continence service.

PMID- 11949373
TI  - April 2001. Journal of tissue viability.

PMID- 11949368
TI  - Theatre, not drama.

PMID- 11949374
TI  - Obstetric care. Is there risk of pressure damage after epidural anaesthesia?
AB  - Anecdotal evidence suggests that there is an increase in the incidence of
      pressure damage to women in labour. This appears to be associated with epidural
      anaesthesia. Epidural anaesthesia used to control pain in childbirth causes loss
      of sensation and a degree of motor block, which removes the women's reflexes and
      ability to reposition to prevent pressure damage. The large amount of fluids
      present during childbirth may also increase the risk of pressure damage,
      especially in association with shear and friction. A combination of unfamiliarity
      of pressure ulcer prevention techniques among midwives, and the type of delivery
      room equipment, that is currently available, may leave young healthy women at
      risk of developing pressure ulcers.

PMID- 11949376
TI  - A patient's perspective: living with facial cancer.

PMID- 11949375
TI  - Morphological architecture and distribution of blood capillaries and elastic
      fibres in the human skin.
AB  - This study was undertaken to clarify the morphological features in the blood
      capillary and elastic fibre distribution of the human skin in terms of
      susceptibility to pressure sore development. Skin tissues were obtained from bony
      areas: the sacrum and ischial tuberosity and non-bony area: the centre of the
      gluteus maximus of 5 aged subjects post mortem for examination using light and
      scanning electron microscopy. It was observed that the sacral skin had finger
      like papillae and underneath the blood capillary loops were most numerous. In the
      ischial skin the dermal papillae consisted of a combination of finger-like and
      trapezoid shapes having moderate density of blood capillaries. In contrast, the
      dermal papillae in the gluteal skin were almost flat, so that the blood
      capillaries were scattered. The size of elastic bundles in the papillary layer of
      the sacral, ischial and gluteal skin ranged from 2 to 3 microns, 5 to 10 microns,
      and 3 to 5 microns, respectively. The elastic fibres were densely distributed in
      the ischial skin while less so in the sacral skin.

PMID- 11949377
TI  - How accurate are pressure ulcer grades? An image-based survey of nurse
      performance.
AB  - We report a descriptive study using a questionnaire and twelve digital
      photographs classified by a consensus panel of experts using the European
      Pressure Ulcer Advisory Panel and Stirling plus digits classifications. The
      expert panel comprised 5 tissue viability specialists/clinical lecturers in
      tissue viability with many years of collective experience and examined 30 images
      over 2 1/2 hours. In general consensus on wound grading was good; in only 2
      images was there insoluble disagreement. Two hundred subjects were recruited from
      a Tissue Viability Society (N = 50), the European Pressure Ulcer Advisory Panel
      (N = 50), five Community Trusts (N = 50) and five Acute Trust (N = 50) in England
      and Wales. The subjects were asked for demographic details (qualifications
      achieved, number of years qualified, employment grade and how their knowledge of
      classification of pressure ulcers has been obtained). The second part of the
      questionnaire asked them to classify twelve digital photographs of pressure
      ulcers using the European Pressure Ulcer Advisory Panel (EPUAP) and the Stirling
      plus digits systems. The study demonstrated that there is considerable lack of
      consensus when pressure ulcers are graded using the Stirling plus digit grading
      system and less disagreement when the EPUAP scale is used. The study also
      demonstrates that the statistical returns from different hospital and community
      units cannot be considered to be directly comparable. Furthermore, the study
      showed that the nurses most educated in pressure ulcer care (Clinical Nurse
      Specialists in Tissue Viability) were the most keen to receive extra education,
      whilst ward nurses were happy with their current knowledge and did not believe
      further education on pressure ulcer grading was necessary.

PMID- 11949378
TI  - The Cochrane Wounds Group.

PMID- 11949379
TI  - [Dietary diversification: neither too early, nor too late....].

PMID- 11949380
TI  - [Disturbing increase in obesity].

PMID- 11949381
TI  - [Public health. Epidemiology and environmental factors in atopic dermatitis].

PMID- 11949382
TI  - [Medical strategy. Clinical aspects and evolution of atopic dermatitis].

PMID- 11949383
TI  - [Therapeutic strategy. Local treatments for atopic dermatitis].

PMID- 11949384
TI  - [Nursing strategy. Thermal treatment, a global management of the atopic child].

PMID- 11949385
TI  - [Loss of a baby and the other children in the family].

PMID- 11949386
TI  - [Nursing strategy. Reflections on multidisciplinary management in pediatric
      psychiatry].

PMID- 11949387
TI  - [Public health. Private swimming pools, children in danger!].

PMID- 11949388
TI  - [Childhood rhythms, from the biological clock to school rhythms].

PMID- 11949389
TI  - [Is adolescence and asthma treatment compatible?].

PMID- 11949390
TI  - [Rescued babies, a catastrophic neurologic prognosis].

PMID- 11949391
TI  - [Writing to exist].

PMID- 11949392
TI  - ["Itinerary of the depressed" or the failure to manage depression].

PMID- 11949393
TI  - [Laragne JournEcritures of 2001].

PMID- 11949394
TI  - [Campaign against drugs and prevention of dependence].

PMID- 11949395
TI  - [The Armel meeting. Survey of the new polyvalent nursing specialists (3)].

PMID- 11949396
TI  - [Internet availability to deal with an event].

PMID- 11949397
TI  - [Body to body nurse-patient].

PMID- 11949398
TI  - [Difficulty in nursing patients with profound deficits].

PMID- 11949399
TI  - [Without stress: art, the psychotic patient, the therapy].

PMID- 11949400
TI  - [Writing by nurses and nursing records, between seeing and knowing].

PMID- 11949401
TI  - [Dancing and mental disorders, a practical experience].

PMID- 11949402
TI  - [Outpatient sector, from philosophy to quality].

PMID- 11949403
TI  - [Strategy in psychotherapy, Palo Alto brief therapy].

PMID- 11949404
TI  - ["No to exclusion, yes to nursing care"].

PMID- 11949405
TI  - [Evaluation of sectorization in psychiatry].

PMID- 11949406
TI  - [Evolution of the distribution of care in mental health].

PMID- 11949407
TI  - [Health care team or nurse supervisor?].

PMID- 11949408
TI  - [Nursing supervisor or health care team?].

PMID- 11949409
TI  - [Teams, attention to the drift!].

PMID- 11949410
TI  - [Nursing team organization: nursing care or administrative responsibility?].

PMID- 11949411
TI  - [Management and politics of nursing care].

PMID- 11949412
TI  - [Psychosociology of organization and management].

PMID- 11949413
TI  - [Times and misfortunes of a team].

PMID- 11949414
TI  - [Team for laughing].

PMID- 11949415
TI  - [Theory as a means for meeting the other].

PMID- 11949416
TI  - [7 capital offenses of relations in psychiatry].

PMID- 11949417
TI  - [Signing a charter by consumers of mental health].

PMID- 11949418
TI  - [The consumer: actor and/or partner?].

PMID- 11949419
TI  - [Preventing violent situations].

PMID- 11949420
TI  - [Questions about accreditation in mental health].

PMID- 11949421
TI  - [National video accounts in mental health, patients present their films].

PMID- 11949422
TI  - A financial plan for seniors. Survival and success in a new economic era.

PMID- 11949423
TI  - Get 'cart'-ed away. A program that brings the dining room to your residents.

PMID- 11949424
TI  - [The clinic, a work of creation].

PMID- 11949425
TI  - [Psydoc-France, the internet site of the French Federation of Psychiatry].

PMID- 11949427
TI  - [A personalized accompaniment model for mentally handicapped persons].

PMID- 11949426
TI  - [Ligne Azur on anxiety in young homosexuals].

PMID- 11949428
TI  - [The clinic and psychiatry, on the road to "more interdisciplinary care"].

PMID- 11949429
TI  - [Principles of the psychiatric nursing clinic].

PMID- 11949430
TI  - [Here.... and now, entreaty for the psychiatric clinic].

PMID- 11949431
TI  - [Clinical work four managing the psychotic patient].

PMID- 11949432
TI  - [Taking the time to understand for nursing care].

PMID- 11949433
TI  - [Support for the family].

PMID- 11949434
TI  - [Mediation and therapeutic aspects in child and adolescent psychiatry].

PMID- 11949436
TI  - [What changes for nursing care in psychiatry and mental health?].

PMID- 11949435
TI  - [Therapeutic workshop. Giving awareness and food].

PMID- 11949437
TI  - [The Piel-Roelandt report approves reorganization of psychiatric care].

PMID- 11949438
TI  - [Toward a definition of nursing care in psychiatry?].

PMID- 11949439
TI  - [Psychiatry and social representations].

PMID- 11949441
TI  - [Eros and thanatos conceptualized on the internet].

PMID- 11949440
TI  - [Piecing together schizophrenia...].

PMID- 11949442
TI  - [Why specialization in nursing care?].

PMID- 11949443
TI  - [Once upon a time there were nurses in the psychiatric sector].

PMID- 11949444
TI  - [Specificity of psychiatric nursing care, needs and symptoms in psychiatry].

PMID- 11949445
TI  - [Apropos of specialism in psychiatry and mental health...].

PMID- 11949446
TI  - [For qualified nursing training in psychiatry and mental health].

PMID- 11949447
TI  - [Nursing competence in psychiatry].

PMID- 11949448
TI  - [Need for specialization].

PMID- 11949449
TI  - [Between lack of funds and "limits", an opportunity?].

PMID- 11949450
TI  - [Choosing specialization?].

PMID- 11949451
TI  - [Supporting the family, practical modalities].

PMID- 11949452
TI  - [The nurse in liaison psychiatry... social aspects].

PMID- 11949453
TI  - [What changes for nursing practice in psychiatry and metal health? 2/2].

PMID- 11949454
TI  - [Reform of nursing care modalities regarding restraint, routine care or
      abrogation of the 1990 law?].

PMID- 11949455
TI  - Expanding the donor pool with living donors.

PMID- 11949456
TI  - Information regarding prostate-specific antigen (PSA) testing was recently
      published in the New England Journal of Medicine.

PMID- 11949457
TI  - Approaching a consensus: psychosocial support services for solid organ
      transplantation programs.
AB  - BACKGROUND: Solid organ transplantation has become an accepted treatment for
      individuals with end-stage organ dysfunction. Criteria are being developed in the
      United States to determine medical eligibility for transplant candidates and
      competencies for transplant centers and physicians. To date, similar criteria for
      psychosocial services have not been developed. DESIGN AND SETTING: We queried
      participants in a specialty psychosocial transplant meeting to determine their
      views of which psychosocial services are essential to the comprehensive care of
      transplant patients in the United States. RESULTS: There was broad based
      multidisciplinary support for proactive pretransplant screening to discern
      individual psychosocial needs; focused pretransplant interventions to improve
      candidacy and future compliance; and posttransplant programs that address
      psychosocial, rehabilitation, and financial issues. CONCLUSION: Among
      psychosocial providers of solid organ transplantation services, there is support
      for expanding routine screening and support services to individuals who are
      candidates for and undergo solid organ transplantation.

PMID- 11949458
TI  - Grief and loss in the workplace.
AB  - Throughout history, death and loss have given rise to social ceremonies and
      commemorative activities that note the death, recognize the place the person
      occupied in society, and assist the bereaved through the process of grief. Each
      culture faces death with its own definition of "appropriate" social-emotional
      reactions, and when death occurs, it provides the occasion for socially
      conditioned grief reactions and mourning practices. Historically, such practices
      have incorporated a set of interrelated people, the majority of whom were very
      knowledgeable of the customs and their purposes. In such a setting, it was
      possible for close kin, friends, distant kin, and acquaintances to come together
      to share their loss and grief. However, people may experience a loss that does
      not fit a socially recognized and sanctioned role. Grief for these people may
      have to remain private. Although they may have experienced an intense loss,
      personally or professionally, they may not be given time off from work or have
      the opportunity to talk about the meaning of their loss. In our modern,
      compartmentalized society, social ceremonies and commemorative activities tend to
      be limited primarily to a small circle of the "proper" bereaved individuals. This
      separation has helped to create a subset of grievers whose legitimacy may not be
      recognized by society as a whole and whose needs are often not addressed.

PMID- 11949459
TI  - Using pressure-limited mechanical ventilation in caring for organ donors.
AB  - Pressure-limited (controlled) ventilation is commonly employed to provide
      mechanical ventilation in the intensive care unit when lung compliance is poor or
      when airway resistance is irreversibly high. Modification of the inspiratory
      expiratory ratio to include inspiratory-expiratory ratio reversal and permissive
      hypercapnia can also be used when lung disease or injury is severe. Because other
      donor organs often can be saved for transplantation even when the lungs have been
      badly damaged, the organ procurement coordinator should adopt pressure-limited
      ventilation as well as inspiratory-expiratory ratio reversal and permissive
      hypercapnia as potentially helpful methods while providing mechanical ventilation
      to selected donors.

PMID- 11949460
TI  - A 5-year analysis of organ donors and recipients in Italy.
AB  - This article describes the improvement of organ donation and transplantation in
      Italy during 1995-1999. In 1999, the mean number of donors per million population
      reached 13.7 in Italy. In addition, an analysis regarding major characteristics
      of donors and recipients is presented, focusing particularly on donor
      characteristics that have changed in the past 5 years. Despite the encouraging
      results, further efforts are required to reach the European mean, which still
      remains higher than the Italian national mean. In particular, an increase of
      organ donation and procurement in regions with a poor activity in this field is
      crucial. A 1999 law on donation and transplantation should help in solving
      problems that continue to affect part of the nation, especially preparing the
      healthcare staff dedicated to organ retrieval to promote organ procurement.

PMID- 11949462
TI  - Increasing family consent for organ donation: findings and challenges.
AB  - There is a growing disparity between the number of organs and tissues needed for
      transplantation and the number available for donation. As a result, thousands of
      people die every year while waiting for a transplant. Much of the shortage can be
      explained by the failure of families to consent to donation. This paper reviews
      the research that has been conducted to elucidate reasons why families deny
      consent. This research, together with theoretically motivated research in the
      areas of persuasion and behavior change, can be used to inform the design of
      educational and promotional campaigns and to guide policy decisions.

PMID- 11949461
TI  - Economic evaluation of kidney transplantation versus hemodialysis in patients
      with end-stage renal disease in Hungary.
AB  - BACKGROUND: Kidney transplantation is generally acknowledged as the more
      clinically effective and more cost-effective option in managing patients with end
      stage renal disease, compared with dialysis. This study looked for confirmatory
      evidence in a Hungarian population. METHODS: Patients (n = 242) with end-stage
      renal disease who received cadaveric kidney transplantation during 1994 were
      followed up for 3 years. They were compared with patients (n = 840) receiving
      hemodialysis who were on a waiting list for transplantation. Data were collected
      retrospectively. Treatments were compared for clinical efficacy and for cost
      effectiveness. RESULTS: At month 36, the standard mortality hazard function was
      3.5 times higher in the group receiving hemodialysis (P < .0001) than in the
      transplant recipients. Average treatment costs per patient over the 3 years were
      also significantly higher (P < .0001) in the hemodialysis group than in the group
      than received transplants. The cost of 1 year gained by transplantation was
      significantly less (P < .0001) than the cost associated with hemodialysis.
      CONCLUSIONS: Compared with hemodialysis, kidney transplantation provides greater
      survival benefits to patients with end-stage renal disease, at less cost.

PMID- 11949463
TI  - Promoting organ donation among high school students: an educational intervention.
AB  - OBJECTIVE: To evaluate the impact of a high school education program to promote
      organ donation awareness. The primary outcomes were intention to discuss organ
      donation with family or friends and actual discussion behavior. DESIGN:
      Longitudinal, observational study. METHODS: 665 high school students filled out
      evaluations at the beginning and at the end of a 1-hour education program. One
      month later, the students were asked to report whether they had discussed
      donation. RESULTS: After the program, knowledge and attitude scores and the
      proportion of students who intended to discuss donation increased (P < .05). At 1
      month follow-up, 48% of students reported actual discussion. Intention has a
      strong, positive relationship with discussion behavior (odds ratio, 8.27; 95% CI,
      3.18-21.51). Ethnicity, sex, and attitude of the students were also predictors of
      donation discussion behavior. CONCLUSIONS: This program appears to be effective
      in prompting discussion of organ donation among high school students.

PMID- 11949464
TI  - Development of a Web site for transplant patient education.
AB  - The Internet is a global communication network used by more than 17.6 million
      adults as a major source of current health information. Both the number of health
      related Web sites and the number of Web users are increasing exponentially as
      well as reports indicating a growth in the number of persons who access the
      Internet specifically to retrieve information about organ transplantation.
      However, few are using this medium for posttransplant educational or psychosocial
      purposes. Armed with this information, as well as a commitment from the
      transplant team, we chose to develop a Web-based educational program to
      facilitate posttransplant care for our transplant recipients. The purpose of this
      article is to describe the planning, development, and implementation of a Web
      based education program for transplant recipients.

PMID- 11949465
TI  - Pretransplant evaluation of a patient with acute intermittent porphyria.
AB  - The pretransplant evaluation of a patient with a rare diagnosis requires
      knowledge of the pathophysiology and the transplant literature. A 55-year-old man
      presented with hypertensive kidney failure and the clinical diagnosis of acute
      intermittent porphyria. Complications of acute intermittent porphyria, which is a
      defect of heme production, are due to the accumulation of heme intermediates
      often precipitated by medications. Based on animal data, cyclosporine is
      considered unsafe in patients with acute intermittent porphyria. As part of the
      pretransplant evaluation, the patient received separate trials of tacrolimus and
      cyclosporine, which did not stimulate his acute intermittent porphyria. Four
      months after a kidney transplant, the patient still had no signs of rejection or
      symptoms of acute intermittent porphyria. This is the first documented patient
      with acute intermittent porphyria who successfully received a kidney transplant
      using tacrolimus. Because of individual variations, pretransplant testing of
      calcineurin inhibitors should be continued in patients with acute intermittent
      porphyria.

PMID- 11949466
TI  - Steroid withdrawal in liver transplant recipients.
AB  - Because of troublesome side effects associated with steroid use, many transplant
      centers have tried to withdraw steroids from stable, solid organ transplant
      recipients. The objective of this study was to evaluate the ability to wean liver
      transplant recipients off steroids, depending on both their primary
      immunosuppressive regimen and their primary disease state. This was a
      retrospective, single-center review of steroid weaning in adult orthotopic liver
      transplant recipients. Based on primary immunosuppression, patients could be
      weaned off steroids similarly if they were taking cyclosporine or tacrolimus
      (53.9% vs 61.4%). When triple immunosuppressive regimens were compared with dual
      regimens, a difference was found in ability to wean patients off steroids (52.4%
      vs 74.5%, P = .001). When steroid weaning was stratified for primary
      immunosuppression and primary disease state, patients with autoimmune-mediated
      diseases (autoimmune hepatitis, sclerosing cholangitis, and primary biliary
      cirrhosis) were less likely to be weaned if they were receiving cyclosporine
      based immunosuppressants (36.8% vs 62.2%, P = .03). In conclusion, it appears
      that a large number of liver transplant recipients can safely be tapered off
      steroids.

PMID- 11949467
TI  - Desire for control, coping, and quality of life in heart and lung transplant
      candidates, recipients, and spouses: a pilot study.
AB  - To understand the interdependence of couples involved in transplantation, both
      partners need to be included in the same study. This pilot study explored the
      desire for control, coping, and quality of life in heart and lung transplant
      candidates, recipients, and spouses, using McCubbin's Double ABCX Model as the
      conceptual basis. Sixty letters were mailed to randomly selected candidates and
      recipients at 2 transplant centers. Twenty-five couples completed a demographic
      sheet and the following surveys: the Desire for Control Scale, the Family Crisis
      Oriented Personal Evaluation Scale, and the Quality of Life Index. There were 9
      pretransplant and 16 posttransplant couples. Analyses included measures of
      central tendency, analysis of variance, t tests, and correlations. There were
      statistically significant differences between pretransplant patients' quality of
      life and all other groups. There were moderate correlations between several
      patient and spouse variables. It was recommended that healthcare professionals
      include both patients and spouses when planning interventions.

PMID- 11949468
TI  - Cancer prevention for transplant recipients.

PMID- 11949469
TI  - What nurses need to know about genetics.
AB  - New genetic discoveries are revolutionizing medical approaches to diagnosis,
      management, and treatment of disease. Because of these changes, nurses need to
      know basic genetic principles and apply them to clinical nursing practice. This
      article describes basic genetics and how nurses can incorporate a genetic focus
      into clinical practice, specifically family history assessment. Ethical
      principles of genetic healthcare also are discussed.

PMID- 11949470
TI  - Will my patient survive this cardiac arrest?
AB  - The authors describe how capnography is used to predict patient outcomes during
      cardiopulmonary resuscitation.

PMID- 11949471
TI  - Families of critically ill patients and the effect of nursing interventions.
AB  - Family needs of critically ill individuals and the nursing interventions to meet
      these needs have spanned 3 decades of research. Researchers have found that
      interventions appear to meet some family needs, but more can be done to provide
      family-centered care and improve patient outcomes.

PMID- 11949472
TI  - You can help your clients change.
AB  - Nurses are in an excellent position to assist clients to change behaviors that
      will improve their health. The client is the expert on what to change and which
      method will work best. Matching your approach to the client's stage of change
      will motivate the client to move along the continuum of change.

PMID- 11949473
TI  - Every nurse is a leader.

PMID- 11949474
TI  - Blood meal acquisition by ticks; molecular advances and implications for vaccine
      development.
AB  - In their quest for a blood meal, hematophagous arthropods must first defeat the
      host's hemostatic defense. Following injury as it occurs when hematophagous
      arthropods insert their proboscis into host skin to feed, the host will attempt
      to stop excessive blood loss through its hemostatic defense mechanism involving
      platelet aggregation, blood clotting and vasoconstriction. To acquire a full
      blood meal hematophagous arthropods inject an arsenal of bioactive enzymes which
      ultimately overpower the host's hemostatic defense. We have looked at a selected
      number of studies on the molecular biology of arthropod anti-hemostatic proteins
      and developed commentaries on the suitability of these molecules as target tick
      vaccine antigens.

PMID- 11949475
TI  - Taenia taeniaeformis larval product induces gastric mucosal hyperplasia in SCID
      mice.
AB  - The effects of intraperitoneal implantation of Taenia taeniaeformis larvae and
      inoculation of in vitro larval products on gastric mucosa of SCID mice were
      investigated in this study. Mice surgically implanted with T. taeniaeformis
      larvae developed slight and moderate gastric hyperplasia. When in vitro cultured
      T. taeniaeformis larval excretory-secretory (TtLES) products containing 1 mg of
      protein were injected daily into mice, they caused gastropathy after 5-7 days.
      Mice injected daily with 0.5 mg of TtLES products also showed slight gastric
      hyperplasia after day 14 and 28. The gastropathy was characterized by reduction
      of both parietal and zymogenic cell number and increased number of alcian blue
      periodic acid Schiff (AB-PAS)-positive cells and by two-fold extension of
      proliferative zone of gastric units. Larval implantation demonstrated a more
      potent effect in inducing gastropathy than did in vitro larval culture products.
      Significant decrease in number of parietal cells with concomitant increase of
      proliferative zone and AB-PAS-positive cell number indicated their important
      roles in inducing the hyperplastic lesion. Similarities with other gastropathies
      indicated that there is a common fundamental regulatory mechanism involved, and
      that the host response may not be specific to parasites. Present study validated
      the induction of gastric mucosal hyperplasia by larval ES products of T.
      taeniaeformis. This proved the hypothesis of previous studies suggesting the role
      of larvae-derived products in inducing gastric mucosal hyperplasia in T.
      taeniaeformis-infected rats.

PMID- 11949476
TI  - Prevalence and intensity of Echinococcus multilocularis in red foxes (Vulpes
      vulpes schrencki) and raccoon dogs (Nyctereutes procyonoides albus) in Otaru
      City, Hokkaido, Japan.
AB  - A survey was done in an attempt to investigate the epidemiological status of
      Echinococcus multilocularis in red foxes and raccoon dogs in Otaru city from June
      to September 1999. Sixty-seven red foxes (Vulpes vulpes schrencki) and 13 raccoon
      dogs (Nyctereutes procyonoides albus) were captured, and postmortem examinations
      were conducted with them. Thirty-eight red foxes (56.7%) and 3 raccoon dogs
      (23.1%) were found to be infected with E. multilocularis. The total biomass of E.
      multilocularis in all infected red foxes and raccoon dogs were 2,817,000 and
      1,515 worms, respectively. Nine of the infected red foxes harboring more than
      100,000 worms accounted for 90.6% of the total biomass. No significant
      differences in the prevalence were observed between male and female, and juvenile
      and adult. However, the worm burden was higher in juvenile than in adult foxes.
      In one of the infected raccoon dogs, mature worms and eggs of E. multilocularis
      were found in the intestine and fecal sample, respectively. This result suggested
      that the raccoon dogs are probably playing a small role in the egg contamination
      of the environment. The validity of coproantigen ELISA for diagnosis of foxes was
      confirmed by comparing the results of autopsy, egg examination and coproantigen
      ELISA using rectal fecal samples.

PMID- 11949477
TI  - Genetic and biological comparison of tick-borne encephalitis viruses from
      Hokkaido and far-eastern Russia.
AB  - We compared the biological properties of Oshima 5-10 (tick-borne encephalitis
      [TBE] virus isolated in Hokkaido, Japan) and Sofjin-HO (Far-Eastern subtype TBE
      virus) including plaque formation, virus replication and virus protein synthesis
      in BHK-21 cell cultures to reveal strain differences. We also determined the
      complete nucleotide sequences of both strains and compared the deduced amino acid
      sequences. Plaques of Oshima 5-10 were smaller than those of Sofjin-HO. Virus
      titers in culture fluid of Oshima 5-10 were 1/100 of those of Sofjin-HO at 9 and
      12 hr after infection. Less viral protein and RNA syntheses of strain Oshima 5-10
      was observed than with Sofjin-HO. Genetic analysis revealed 1.4% of amino acids
      to differ with Sofjin-HO. No difference between the two strains was detected in
      the motif sequence of the viral enzyme, cleavage sites of viral protein or
      glycosylation sites of NS1.

PMID- 11949478
TI  - King's conceptual system and theory of goal attainment: past, present, and
      future.
AB  - Imogene King is universally recognized as a pioneer of nursing theory
      development. Her interacting conceptual system for nursing and her theory of goal
      attainment have been included in every major nursing theory text, are taught to
      thousands of nursing students, form the basis of nursing education programs, and
      are implemented in a variety of service settings.

PMID- 11949479
TI  - Cocreating anew in public health nursing.
AB  - Since the tragic events of 9/11/01, public health nursing is undergoing rapid
      change with increased public awareness and a need for programs and protocols
      addressing issues such as bioterrorism, public safety, and continuing healthcare
      service in community settings. What is the role of professional nursing in these
      settings during turbulent times? This column focuses on these issues from the
      lens of the human becoming school of thought with discussion of the embedded
      ethical opportunities and challenges that require contemplation.

PMID- 11949480
TI  - Praxis as a mirroring process: teaching psychiatric nursing grounded in Newman's
      health as expanding consciousness.
AB  - The purpose of this column is to describe the application of Newman's theory of
      health as expanding consciousness in nursing education. The authors examine the
      value of mirroring presence, self-reflection, appreciation of meaning and
      pattern, and creative approaches to student learning in their care of clients
      with chronic mental illness. Praxis as the basis for caring in the human health
      experience is discussed in this newly developed teaching-learning model.

PMID- 11949481
TI  - Ebola at Mbarara, Uganda: aesthetic expressions of the lived worlds of people
      waiting to know.
AB  - The Ebola epidemic of 2000 was a disastrous experience for the people of Uganda.
      Prior outbreaks in neighboring African sub-Saharan countries heightened the
      realization of death from this devastating disease. Waiting to know is a
      phenomenon described as an excruciating inactivity uniquely experienced by
      individuals who were exposed to persons with Ebola but who had not yet exhibited
      signs and symptoms of the disease. In the recent Ebola epidemic in Uganda,
      contact persons described their experience of waiting to know as "helplessness in
      anticipation and fear of dying or premature death; agonizing and languishing over
      losing relatives, friends, and loved ones; trusting no one; and helplessness and
      hopelessness with the persisting time." In this column, these experiences will be
      discussed, and visual artworks will further illustrate the lived experience of
      waiting to know. Human and artistic expressions facilitate understanding of lived
      experience, and understanding is known to inspire meaningful, compassionate, and
      competent nursing practice.

PMID- 11949482
TI  - The nurse theorists: 21st-century updates--Madeleine M. Leininger.
AB  - This edited transcript of an interview with Madeleine Leininger presents
      Leininger's recent thoughts about the development and current state of the
      discipline of nursing, the development of the theory of culture care diversity
      and universality, methods for nursing research, mentorship, and transcultural
      nursing practice.

PMID- 11949483
TI  - The pattern of the becoming-self in death and dying.
AB  - As part of a triangulated study that examined psychological adaptation in home
      hospice patients, the grounded theory method was used to generate social
      psychological processes of dying. The pattern of the becoming-self was one of
      seven patterns that emerged. The responses and reactions of 15 dying persons
      described a pattern that was shaped by self-integration, inner cognition,
      creation of personal meanings, and connection to others and a higher being. The
      becoming-self supported humanism and veritivity as defined in adaptation nursing
      theory.

PMID- 11949484
TI  - One-to-one teleapprenticeship as a means for nurses teaching and learning Parse's
      theory of human becoming.
AB  - This research investigated one-to-one teleapprenticeship as a means of teaching
      and learning Parse's theory of human becoming. Teleapprenticeship is defined as a
      one-to-one learning relationship, conducted entirely by E-mail, in which a mentor
      teacher guides a learner in the construction of knowledge about a domain.
      Seventeen nurses (6 teachers and 11 learners) engaged in dialogue journaling
      about the theory relative to the learners' nursing practice. The
      teleapprenticeship experience was found to be useful for supporting a nurse in
      the study of theoretical aspects but may be insufficient for helping to develop
      proficiency in the practice methodology of the theory.

PMID- 11949485
TI  - Humor and health in early adolescents: perceived field motion as a mediating
      variable.
AB  - The purpose of this study was to test a mediational model, developed within the
      science of unitary human beings, by examining the relationship between humor and
      eudaimonistic health conception in early adolescents and by examining the extent
      to which perceived field motion mediated this relationship. The sample consisted
      of 136 adolescents, aged 12 to 14, who responded to instruments measuring humor,
      perceived field motion, and eudaimonistic health conception in classroom
      settings. Correlational analysis supported the three hypothesized relationships.
      Regression analyses indicated that perceived field motion was one mediator of the
      relationship between humor and eudaimonistic health conception.

PMID- 11949486
TI  - Testing a theory of decision-making derived from King's systems framework in
      women eligible for a cancer clinical trial.
AB  - The purpose of this study was to test an explanatory theory of decision-making in
      women eligible for a cancer clinical trial. The theory derived from King's
      framework proposed that the concepts of uncertainty, role functioning, and social
      support relate to emotional health (hope and mood state), which in turn relates
      to the treatment decision. A correlational study design was used to test the
      theory in a sample of 40 women. Findings provided empirical evidence of the
      adequacy of King's framework and supported, in part, theorized relationships
      among the critical factors. However, these factors did not illuminate the
      treatment decision.

PMID- 11949487
TI  - Nursing with a global view.

PMID- 11949488
TI  - The global context of nursing: a human becoming perspective.
AB  - When one considers global health issues from the natural science worldview, it is
      with a belief that no one person can have any significant influence, hence, a
      sense of powerlessness and disconnection. In this column, though, the authors
      assert that when one's perspective is the human science paradigm, and
      particularly, the human becoming theory, one person can and does make a
      difference in global health. The authors discuss the human becoming perspective
      using the metaparadigm concepts of human, health, and environment, and also,
      nursing practice guided by the theory. Informed by this perspective, they then
      explore political implications for global nursing and health.

PMID- 11949489
TI  - Mentoring moments.

PMID- 11949490
TI  - Lyrical language and nursing discourse: can science be the tool of love?
AB  - Lyricism is a quality of discourse expressing intensely personal feeling or
      emotion. It is historically associated with romanticism, which involves the
      imagination and emotions, the use of autobiographical material, the exaltation of
      a common humanity, and an appreciation of nature. The language of a science
      conveys the meaning, significance, and utility of concepts among scholars,
      practitioners, and the general public. It is incumbent upon nurses to attempt to
      represent in our disciplinary language the realities lived by people, that is, to
      apprehend, describe, and explain the full breadth and diversity of human
      phenomena, guided by the discipline-wide focus on the wholeness of the human
      being. The language of objectivistic science cannot do this. Even in contemporary
      qualitative research there are limitations in achieving such a representation.
      This column therefore calls for greater attention to lyrical discourse in nursing
      science and outlines the potential benefits in nursing theory development,
      research, and practice. Encouragement of lyrical discourse in nursing science is
      consistent with the contemporary movement toward a dialogical rationality. It is
      posited that, if the ethos of nursing is rooted in love of humanity, lyrical
      discourse may be one way for nursing to pursue its mission to serve humankind.

PMID- 11949491
TI  - [Total hip replacement: a criterion of coxarthrosis evaluation?].

PMID- 11949492
TI  - [Index of hip prosthesis in coxarthrosis].

PMID- 11949493
TI  - [Functional rehabilitation, self-rehabilitation and patient education in
      arthrosis of the lower limb].

PMID- 11949494
TI  - [Impact of the education of a patient with arthrosis].

PMID- 11949495
TI  - [Current therapeutic possibilities in the treatment of arthrosis].

PMID- 11949496
TI  - [Computer-assisted surgery in orthopedics].

PMID- 11949497
TI  - [Animal tuberculosis].

PMID- 11949498
TI  - [Design and birth of drugs].
AB  - Today the design of new clinical entities uses highly sophisticated techniques.
      This design is a step by step procedure: first selection and validation of the
      therapeutic targets, where the contribution of genomics is very important; then,
      setting up the different screening tests. This step permits to detect the
      potentially active molecules, which will be optimised, before being tested in
      healthy volunteers and then in patients.

PMID- 11949499
TI  - [From the chemical product to the authorization of drug marketing].
AB  - A great number of highly qualified specialists are involved in the drug
      development process, mainly chemists, galenic and pharmacokinetic experts,
      pharmacologists and toxicologists. The 7 to 15 years development process implies
      preclinical studies in thousands of animals as well as clinical studies in about
      3,000 patients. Various mandatory studies, regulatory requirements as well as a
      drug assessment process lead to the possible marketing authorization approval.
      The drug assessment process usually leads to a sound assessment of pharmaceutical
      quality of clinical benefit in each indication proposed; yet, occasionally, the
      assessment of safety is incomplete. Performing phase IV studies, collecting
      pharmacovigilance data is a requirement in the future. The prescriber of a newly
      approved drug must remain highly watchful.

PMID- 11949500
TI  - [Role of drugs in therapeutic strategies].
AB  - When a medication receives an authorization for the release onto the market, it
      is necessary to determine the place that it will occupy in the therapeutic
      strategies with 2 regulatory steps: The Commission de la transparence (Commission
      for Transparency) gives an opinion on the target population, the placing in the
      therapeutic strategies, the level of medical benefit for patient, the restriction
      or not to hospital usage, and the inclusion in the national medical insurance
      reimbursement scheme for the medications that are not reserved to hospitals. The
      second step is the passage before the Comite economique du medicament (Medical
      Economics Committee) that fixes the price of re-emboursement of the product. The
      place that the medication will occupy depends on the expectations of the doctors,
      and through them the patients, and the promotional efforts of the pharmaceutic
      industry. The publicity is framed by a control a posteriori that relies on the
      advertising elements diffused in the press as much as on the documents presented
      or put to the doctors. The final place of a given medication in the therapeutic
      strategies depends on numerous factors that can lead to 2 specialised medicines
      having the same indications occupying very different parts of the market, without
      the prescribers being capable to easily justify the reasons that makes them
      choose one molecule over another.

PMID- 11949502
TI  - [Drug vigilance].
AB  - The goal of drug vigilance is to identify, analyse and anticipate adverse
      reactions resulting from the use of a drug. It is of utmost importance to ensure
      that a drug remains safely used, and to update its prescription when necessary.
      Vigilance is based on professional judgments by specialists who flag putative
      side effects to the network. To ascertain causality between drug use and possible
      side-effects, the available evidence is discussed within the vigilance network,
      closely involving the health professional who originally identified a possible
      effect, and with reference to the French drug vigilance database, as well as the
      existing relevant literature. The possibility of a side-effect triggers an alarm,
      and generates an investigation, which must often he completed by an
      epidemiological analysis when the risk associated with the drug is low. Drug
      vigilance is crucial to public health. It currently collects data both from the
      relevant units in pharmaceutical companies and the public drug vigilance
      networks.

PMID- 11949501
TI  - [Good and bad fortunes of drugs].
AB  - A drug's lifetime, whether it is short or long, may go through fantastic new
      developments. Such is the case with beta-blockers, some of which have long been
      prescribed in heart failure before having made the definite proof of their
      efficacy, provided they are used carefully regarding the Good Product Use. On the
      other hand, the development of mibefradil, a calcic antagonist prescribed in the
      treatment of hypertension and angina pectoris, was stopped abruptly a few weeks
      before its launching because of the occurrence of serious side effects in
      patients suffering from heart failure. These examples, which are taken amongst
      others, clearly show the difficulties encountered by pharmaceutical companies
      that are concerned in putting forward innovative, efficacious, and ... secure
      drugs.

PMID- 11949503
TI  - [Reassessment of drugs].
AB  - The usefulness of a product can vary considerably over the course of time.
      Nothing is more arduous than to have to re-evaluate a medication but nothing is
      more necessary. The Legal Information of market authorization can become obsolete
      and necessitate a re-evaluation, a harmonisation with the products of the same
      therapeutic class, in short, a re-writing. The notion of the level of
      classification of drug utility can vary: arrival of new products that are more
      efficacious, publication of negative data concerning the efficacity or security
      of one or more products of the class. The decision to include in the national re
      emborsement scheme, the fixation of the level of re-emborsement, and the price of
      the product can vary. This necessary fluidity comes up against the unwieldy
      nature of the procedures that must be put in place in order to carry out a re
      evaluation in the proper conditions and in not distorting them at the time of
      active competition of the drug companies.

PMID- 11949505
TI  - [Paradoxes].

PMID- 11949506
TI  - [Ligament and meniscal lesions of the knee and ankle].

PMID- 11949504
TI  - [Drugs in Europe].
AB  - Since 1995, a new system for authorization of medicinal products has been
      implemented in Europe. It is based on the collaboration of different actors which
      are the competent authorities of the member States, the European Agency for the
      evaluation of medicinal products and the European Commission. These partners are
      differently involved in one or the other of the 2 European procedures
      (centralised and mutual recognition) in order to allow the assessment of
      efficacy, safety and quality of new medicinal products. Description of the 2
      procedures (scope, time-frame, characteristics of the decision, role of different
      stakeholders, advantages or difficulties...) allows to foresee the points which
      should be improved in the next revision of the legislation.

PMID- 11949507
TI  - [Multiple sclerosis].

PMID- 11949508
TI  - [Impairment of visual disfunction. Diagnostic approach].

PMID- 11949509
TI  - [Limping and gait disorders in children. Diagnostic approach].

PMID- 11949510
TI  - [Deep venous thrombosis and pulmonary embolism].

PMID- 11949511
TI  - [Jaundice. Diagnostic approach].

PMID- 11949512
TI  - Tools and systems for improved outcomes. Institute of Medicine report on
      healthcare quality.

PMID- 11949513
TI  - Outcomes measurement in cardiac rehabilitation: from observation to application.

PMID- 11949514
TI  - Expanding American Nurses Association nursing quality indicators to community
      based practices.
AB  - Continuing its commitment to patient care quality, the American Nurses
      Association appointed a committee in 1997 to expand nursing-sensitive quality
      indicators beyond acute care. This article is the final report describing the
      processes used to identify a core set of community-based quality indicators
      relevant to nurses across the care continuum and identifies next steps. The
      indicator categories are (a) change in symptom severity, (b) strength of the
      therapeutic alliance, (c) utilization of services, (d) client satisfaction, (e)
      risk reduction, (f) increase in protective factors, and (g) level of
      function/functional status. Potential indicators requiring further research and
      development are also described.

PMID- 11949515
TI  - Developing an outcomes management program in a public health department.
AB  - A local public health department planned and implemented a comprehensive outcomes
      management program over a 5-year period. Critical components included commitment
      of leadership and staff, collaborative decision-making related to clinical record
      software selection, extensive staff training and support in documentation and
      automation, and ongoing evaluation. This successful program now provides reliable
      and valid quantitative outcomes data for the department.

PMID- 11949516
TI  - A collaborative approach to integrating outpatient and inpatient transplantation
      services.
AB  - This article describes one hospital's experience in using a collaborative
      approach to integrate outpatient and inpatient care services for the management
      of end-stage organ failure by the use of a dedicated transplantation ambulatory
      outpatient service. Fostering multidisciplinary collaboration requires effective
      communication, sharing of expertise, interdependence, teamwork, and mutual goals.
      These five elements of collaboration have been an effective strategy to integrate
      care across different practice settings while promoting continuity of patient
      care. Although each healthcare member works independently, it is through the
      combined efforts of all team members that anticipated outcomes can be achieved.
      Collaboration has been a process by which we have enhanced the ability of
      different professionals to work together in achieving patient, system, and
      institutional goals.

PMID- 11949517
TI  - Effects of a culturally sensitive breast self-examination intervention.
AB  - The purpose of this study was to examine the effects of a culturally sensitive
      breast self-examination (BSE) program on the frequency and proficiency of BSE
      practices among African American women, ages 20 to 40 years. Phase I,
      qualitative, used focus groups to refine components for a BSE program. Phase II,
      quasi-experimental, assigned 89 African American women to treatment and
      comparison treatment groups. The dependent variables were BSE frequency and
      proficiency (technique and lump detection). Data were analyzed (n = 71) using
      descriptive and paired t test statistics. The culturally sensitive program did
      not increase BSE frequency more than the comparison program. Women in both groups
      made significant improvement.

PMID- 11949519
TI  - Clinical outcomes in transition program for older adults with hip fracture.
AB  - Measuring and managing outcomes across the continuum of care has been a major
      task for healthcare organizations over the past decade. Care of older adults with
      hip fracture and their transition to the community is particularly challenging.
      This article describes a program designed specifically to meet these challenges.
      The goals of the transition program were to promote improved clinical outcomes,
      reduce acute care resource utilization through early discharge and provision of
      cost-effective home care, and maintain or improve patient satisfaction. Results
      of the outcome analysis demonstrated successful goal attainment. The strength of
      the outcome evaluation is that it links both a qualitative and quantitative
      approach, providing a richer and more holistic view of the client experience.

PMID- 11949518
TI  - Data mining methods for improving birth outcomes prediction.
AB  - Data mining is a research method that is increasingly being used to predict
      clinical outcomes, for example, cancer or AIDS survival, diagnostic accuracy in
      abdominal pain or brain tumors, and much more. In clinical practice, predicting
      which patients will deliver preterm versus full term remains a complex clinical
      problem for families and the healthcare system. Exploratory data mining was used
      for predicting birth outcomes in a racially diverse sample (n = 19,970). Duke
      University provided data (1622 variables) for data mining methods that found 7
      demographic variables yielded .72 area under the curve for receiver operating
      characteristic (ROC) analyses, suggesting that a parsimonious set of preterm
      birth outcomes predictors may be possible. Improved prediction is needed for
      interventions to be appropriately targeted for improved birth outcomes
      management.

PMID- 11949520
TI  - Does social responsibility still exist?

PMID- 11949521
TI  - MGMA testifies at first congressional hearing on Medicare payment cuts.

PMID- 11949522
TI  - What's it take for physicians to reach peak earnings? Time.

PMID- 11949523
TI  - The benefits of a practice-managed Web site.

PMID- 11949524
TI  - Decompensation. Avoiding out-of-state workers' compensation problems.

PMID- 11949525
TI  - Write power. Using a journal for professional development.

PMID- 11949526
TI  - To have and to hold--but for how long? Guidelines for records retention.

PMID- 11949527
TI  - Physicians make the move to owners. InterMountain Health Group case study.

PMID- 11949528
TI  - Navigating uncertain waters. Strength of culture, other factors help successful
      groups stay the course.

PMID- 11949529
TI  - Don't be demoralized ... analyze. Examine revenue to improve your health plan
      contracting efforts.

PMID- 11949530
TI  - Care coordination. Helping physicians improve care for the chronically ill.

PMID- 11949531
TI  - Missing the middleman. Disintermediation challenges to doctor-patient
      relationships.

PMID- 11949533
TI  - Should you seek that seal of approval? Accreditation for medical group practices.

PMID- 11949532
TI  - If the nation's in recession, then so is your practice.

PMID- 11949534
TI  - Work it out. Managing contractual relations with mediation.

PMID- 11949535
TI  - Mix and match. How capitation and practice size affect health work force.

PMID- 11949536
TI  - Evaluating vehicle inspection/maintenance programs using on-road emissions data.
      The Atlanta Reference Method.
AB  - On-road remote sensing data is an increasingly popular source of evaluation
      information for vehicle inspection/maintenance (I/M) programs. This article
      conducts one such remote sensing data evaluation for the Atlanta, Georgia, I/M
      program. The reference method involves comparing emissions differences in I/M and
      non-I/M fleet vehicles with those predicted by a regulatory computer model.
      Assuming that on-road emissions differences represent observed effectiveness and
      model-predicted emissions differences represent effectiveness goals, the Atlanta
      enhanced I/M program appears to be achieving 83% of its targeted emissions
      reductions. The method compares favorably with other remote sensing evaluation
      methods in its ability to be applied over time and its relatively small sample
      size requirement. The chief limitation to the approach is its reliance on a
      representative non-I/M fleet, which may differ in characteristics for which
      controls are difficult to locate. Such potential confounding factors include
      discrepancies in maintenance trends, socioeconomic conditions, and vehicle
      quality.

PMID- 11949537
TI  - Data quality in evaluation of an alcohol-related harm prevention program.
AB  - The authors report the reliability and convergent validity in a sample of college
      students for 27 composite scales and two items covering alcohol use, cigarette
      smoking, marijuana use, and other drug use; beliefs relating to alcohol use;
      perceived norms for alcohol-related behavior; harm prevention skills; intentions
      to take prevention action; harm prevention action taken; risk taken; experienced
      harm; and other health-related behaviors and person characteristics. Data quality
      assessment strategies and missing data procedures were illustrated for large,
      multivariate, longitudinal data sets. Results indicate 23 of the 27 composite
      scales had at least acceptable reliability, and the remaining 4 composite scales
      had at least marginally acceptable reliability. At least moderate construct
      validity was demonstrated for 25 scales.

PMID- 11949538
TI  - The impact of an integrated family planning program in Russia.
AB  - In 1995, the U.S. Agency for International Development implemented an integrated
      program of family planning education and services in six Russian cities to
      increase physicians' and women's contraceptive knowledge and change current
      contraceptive use. Large population-based surveys of women ages 15-44 were
      carried out at the beginning of project implementation (in 1996) and 3 years
      later in two project sites and a comparison site. Results from these surveys
      indicate that project activities affected women's knowledge of family planning
      methods, and caused women to have more favorable attitudes toward modern
      contraception. In addition, abortion rates decreased in project sites while
      remaining virtually unchanged in the comparison site. Because of uneven
      implementation of project interventions in the demonstration sites, however, the
      intervention's actual impact on abortion rates remains unclear.

PMID- 11949539
TI  - Grade-induced beliefs about undergraduate generalist social work practice
      competency.
AB  - Standardized criterion-referenced achievement testing of undergraduate generalist
      social work knowledge based on correct answers to specific questions is compared
      to several norm-referenced measures of student learning, including student self
      reports and the instructor-imposed cumulative grade point average (GPA). Two
      hypotheses are tested, namely, (a) norm-referenced measures systematically
      overstate content knowledge, and (b) student perception or belief about the
      ascribed meaning of the GPA inflates self-rated attainments. The implications of
      additional confirming evidence for the hypotheses are explored with a view to
      limiting the number of social workers with undergraduate degrees who are
      permitted to enter the field each year overconfident about their knowledge and
      practice capabilities.

PMID- 11949540
TI  - A growing, pruritic plaque on the thigh. Majocchi's granuloma with secondary
      tinea incognito.

PMID- 11949541
TI  - SCHIP: a far-reaching health insurance program for children--and adults.

PMID- 11949542
TI  - Practical evaluation of pediatric heart murmurs.

PMID- 11949543
TI  - A first survey. Measuring burnout in emergency medicine physician assistants.
AB  - Using the Maslach Burnout Inventory (a device used in prior studies on emergency
      physicians) and the EMPA Demographic, Work, and Lifestyle Characteristics Survey,
      we assessed the burnout levels of emergency medicine physician assistants (EMPAs)
      and the presence of characteristics associated with higher burnout levels. Fifty
      nine percent had moderate or high burnout levels on the Emotional Exhaustion
      subscale; 66% on the Depersonalization subscale; and only 34% on the Personal
      Accomplishment subscale. Several associations were found between EMPA burnout and
      individual characteristics, including insomnia and low satisfaction with
      physician supervision. Similarities were noted with regard to burnout among EMPAs
      and emergency physicians.

PMID- 11949544
TI  - From the outside looking in.

PMID- 11949545
TI  - Subungual hematoma evacuation.

PMID- 11949546
TI  - Apgar scoring: its use and meaning for today's newborn.
AB  - Apgar scoring is a common and accepted practice used for evaluating newborns
      immediately after delivery. After its development by Dr. Virginia Apgar in the
      late 1940s/early 1950s, its use and meaning have evolved over the past five
      decades. Today, every baby born in a U.S. hospital is given an Apgar score. With
      advances in neonatology and improved survival rates for infants with lower
      gestational ages, a new or revised scoring system may be warranted in order to
      more appropriately evaluate the extremely preterm infant. In addition, the
      predictive capabilities of Apgar scoring must be considered with caution for all
      gestational age groups.

PMID- 11949547
TI  - Lasers in medicine: treatment of retinopathy of prematurity.
AB  - Lasers are a unique surgical tool, but what actually are they? This article
      answers that question and describes how lasers work and how they are being used
      in medicine. Retinopathy of prematurity (ROP) then is defined. Cryotherapy, a
      surgical procedure often performed on ROP patients, is reviewed and compared to
      photocoagulation, a form of laser therapy. Photocoagulation and its complications
      are then discussed.

PMID- 11949548
TI  - Neonatal laboratory blood sampling: comparison of results from arterial catheters
      with those from an automated capillary device.
AB  - PURPOSE: To compare neonatal laboratory results from capillary blood samples
      drawn using the Tenderfoot automated capillary sampling device with those drawn
      through arterial catheters. DESIGN: Prospective, paired comparisons of laboratory
      results from capillary and arterial blood. SAMPLE: Twenty-one infants being cared
      for in an NICU and having indwelling arterial catheters through which a variety
      of predominantly glucose-containing fluids were being administered. MAIN OUTCOME
      VARIABLES: Statistical comparisons of paired capillary and arterial results of
      pH, PO2, PCO2, lactate, sodium, potassium, ionized calcium, and hematocrit.
      RESULTS: No capillary-arterial differences were observed for pH, PCO2, lactate,
      or sodium. Although capillary results were slightly, but significantly (p < .01),
      higher for potassium (+0.4 mEq/liter), ionized calcium (+0.47 mg/dl), and
      hematocrit (+4 percent), these differences fell within acceptable Clinical
      Laboratories Improvement Act (CLIA) performance criteria. Markedly lower PO2 (
      30.2 mmHg) and glucose (-61 mg/dl) values were observed with capillary sampling.
      With the exception of results for PaO2 and plasma glucose, capillary blood drawn
      using the Tenderfoot automated device yields laboratory results comparable to
      those from blood drawn from arterial catheters as assessed by CLIA performance
      criteria.

PMID- 11949549
TI  - Identifying high-risk pregnancies and deliveries.

PMID- 11949550
TI  - One nurse looks back.

PMID- 11949551
TI  - Thoughts on surfactant administration.

PMID- 11949552
TI  - Heat and hot water scarce in Tajikistan, but not compassion.

PMID- 11949553
TI  - Risk warning. Broken glass capillary tubes pose danger from bloodborne pathogens.

PMID- 11949554
TI  - Genetic tests explored for hearing, communication disorders.

PMID- 11949555
TI  - Neonatal skin care.

PMID- 11949557
TI  - Developing leadership skills in staff nurses.

PMID- 11949556
TI  - Considerations for touch and massage in the neonatal intensive care unit.

PMID- 11949558
TI  - Parathyroids: the forgotten glands.
AB  - Symptomatic calcium disorders--most notably, hypocalcemia--are common problems in
      preterm and certain term infants. Many factors predispose susceptible neonates to
      hypo- or hypercalcemia, but in many cases, the root of the problem is altered
      function of the parathyroid glands. Parathyroid gland dysfunction may affect
      calcium homeostasis and alter physiologic functioning, resulting in significant
      clinical symptoms. A review of how the parathyroid glands and parathyroid hormone
      affect calcium balance and of the problems that result from altered function
      promotes a better appreciation of the important role played by these sometimes
      "forgotten" glands in maintaining normal neonatal physiologic functioning.

PMID- 11949559
TI  - Are you working well?

PMID- 11949560
TI  - Winning ways.

PMID- 11949561
TI  - Band aid.

PMID- 11949562
TI  - Bug busting.

PMID- 11949566
TI  - Control and restraint training in acute mental health care.
AB  - AIM: This article describes the first stage of a research project. The aim was to
      establish the frequency and pattern of assault, and the use, effectiveness and
      safety of breakaway and restraint techniques, in an intensive care unit for
      mental health patients. Views of nursing staff with regard to training and the
      use of restraint were also explored. METHOD: The study involved a qualitative
      analysis of 346 adverse incident reports in a 16-bed mental health intensive care
      unit over a 32-month period. Data on staff perceptions of breakaway and restraint
      techniques were collected using face-to-face, semi-structured interviews with 19
      nurses. RESULTS: Of the 85 incidents identified, 11 were attempted assaults
      intended to cause physical harm to a member of staff. The remaining 74 involved
      actual contact with a client or an object held or thrown by him or her. Punches
      and kicks were the most common forms of assault reported. There were 66 incidents
      of restraint recorded. The most common reason for this was attack or attempted
      attack on a member of staff. CONCLUSION: Staff were generally satisfied with the
      training they received on control and restraint courses, however some problems
      were identified. There appears to be a mismatch between patterns of assault and
      preparation for dealing with assaults. Aspects of restraint, such as
      establishment of holds, are problematic in application. Although punches and
      kicks were the most common form of assault reported, less time is spent on these
      during training.

PMID- 11949567
TI  - The impact of oral health on nutritional status.
AB  - In this article, the author argues that the assessment of oral health in older
      people is important as it can indicate signs and symptoms of oral and systemic
      disease.

PMID- 11949569
TI  - Health promotion and learning disability.
AB  - The author argues that nurses should adopt a health promotion role with people
      who have learning disabilities. This will enable them to build partnerships with
      patients and develop caring relationships.

PMID- 11949568
TI  - The nursing view of clinical governance.
AB  - This article outlines the findings from three RCN discussion groups, which aimed
      to gain an understanding of how nurses were responding to clinical governance and
      to what extent they were involved in its implementation. The article focuses
      mainly on the third round with clinical nursing staff, senior managers and
      clinical governance facilitators. Three key issues were reported by nurses taking
      part in all three rounds of discussion groups. First, there is the need to raise
      awareness among frontline clinical staff to ensure that clinical governance
      becomes recognised as an integral part of their clinical workload rather than
      being seen as an optional extra. The second issue is the need to change
      organisational culture to make it more receptive to clinical governance. Third is
      the requirement to establish greater levels of partnerships between clinicians
      and managers, patients and professionals, and professional groups. However, the
      authors caution that the organisational cultural change necessary for the
      successful implementation of clinical governance is not as straightforward as the
      literature appears to suggest, and argue that this remains a key challenge for
      organisational leaders, managers and clinical staff.

PMID- 11949574
TI  - Distraction osteogenesis for augmentation of the deficient alveolar ridge.
AB  - Distraction osteogenesis is a technique in which new bone generation and soft
      tissue proliferation are achieved by means of distraction or lengthening of the
      preexisting native bone. This technique has its origins in orthopedic surgery and
      has been used more extensively in the craniofacial region over the past few
      years. It has been successfully used to treat patients with mandibular,
      maxillary, and midface deficiencies, and its use for augmentation of the resorbed
      or atrophic dento-alveolar ridge is currently being explored. In this report, the
      technique of alveolar distraction is discussed and two cases are presented in
      detail.

PMID- 11949573
TI  - High-tech profiles of 2002.

PMID- 11949575
TI  - Clone and organize your practice with high tech(nique).

PMID- 11949572
TI  - CAD/CAM: overview of machines and materials.

PMID- 11949576
TI  - A novel method for non-tack compaction of resin composites.

PMID- 11949578
TI  - Drug information databases for the 21st century: a review of the most popular
      applications.

PMID- 11949577
TI  - Open wide.

PMID- 11949579
TI  - Technical innovations in dentistry.

PMID- 11949580
TI  - How many gadgets can fit in a dental treatment room?

PMID- 11949584
TI  - [Management of bronchiolitis in infants].

PMID- 11949585
TI  - [Infant transfer, when there is a crib shortage].

PMID- 11949586
TI  - ["Ile-de-France Bronchiolitis", a respiratory therapy health care project].

PMID- 11949587
TI  - [Bronchiolitis in small children in practice].

PMID- 11949588
TI  - [Physical therapy approach in the disturbed child].

PMID- 11949589
TI  - [Morocco, a mosaic of child health services].

PMID- 11949590
TI  - [35 hours at public hospitals, the first step is crossed].

PMID- 11949591
TI  - [Child welfare propositions].

PMID- 11949592
TI  - [The tragedy of the forgotten].

PMID- 11949593
TI  - [The pertinence of association in mental health].

PMID- 11949595
TI  - [Kelpsy, a site unlike all the others].

PMID- 11949594
TI  - [The nurse in psychiatry, specificity or specialty?].

PMID- 11949596
TI  - [Association of consumers for better care].

PMID- 11949597
TI  - [Legal aspects of patient rights in psychiatry].

PMID- 11949598
TI  - [Nursing care strategy. Disclose the diagnosis?].

PMID- 11949599
TI  - [Asking patients for their opinion, what is the change?!].

PMID- 11949600
TI  - [11th commandment: you shall consider the sick person!].

PMID- 11949601
TI  - [The viewpoint of consumers and their families (interview by Christian
      Bourdeux)].

PMID- 11949602
TI  - [Supports for the family, experience and limits].

PMID- 11949603
TI  - [Psychopathological and psychoanalytic aspects of drug dependence].

PMID- 11949604
TI  - [Toward reinforcement of the rights of ill persons].

PMID- 11949605
TI  - [35 hours, why do it?].

PMID- 11949606
TI  - [What connection between mental health personnel?].

PMID- 11949607
TI  - Peer reviewing papers for a journal--is it worth it?

PMID- 11949608
TI  - Case-mix adjusted incidence of pressure ulcers in acute medical and surgical
      wards.
AB  - Pressure ulcers cause considerable pain and suffering and are also a very
      expensive drain on NHS funding. Measuring prevalence is particularly useful for
      guiding use of resources whereas incidence is an outcome indicator of quality of
      care. Patients and illnesses vary and it may be misleading to make assumptions
      based on crude incidence figures. A system of case-mix adjustment has been
      developed in Glasgow (GPSISS). This study used GPSISS to measure case-mix
      adjusted incidence of pressure ulcers in over 15,000 acute hospital patients. The
      incidence of pressure ulcers ranged from 1.1% to 2.7%. These low rates, and the
      time cost and effort involved in ensuring quality data, suggests that significant
      differences in quality of care may be demonstrated more quickly using processes
      rather than outcomes and may more directly identify where changes in practice are
      required.

PMID- 11949609
TI  - The development of a novel technique for predicting the exudate handling
      properties of modern wound dressings.
AB  - Numerous methods have been developed for measuring the absorbency of wound
      dressings but many are product specific and do not permit comparisons between
      different dressing types. Existing methods are also of limited value when
      assessing how a dressing is likely to perform in clinical practice. A new wound
      model has been developed that overcomes both of these problems. It facilitates
      direct comparisons between products that are different in structure and
      composition and provides, perhaps for the first time, a method that may be used
      to predict the time for which dressings might be expected to remain effective on
      exuding wounds. The historical background to the introduction of test methods for
      surgical dressings is briefly reviewed, and the development of the new wound
      model is described. Some preliminary results that illustrate the potential value
      of this new technique are also presented.

PMID- 11949610
TI  - An instrument for in-service testing of mattresses.
AB  - It is widely recognised that mattresses have a finite life-span. In particular,
      hospital mattresses, typically made from polymer foam materials, are known to
      degrade over a period of years. Fatigue of a mattress in this way leads to a
      phenomenon known as 'bottoming'. This refers to the yielding of the mattress to
      such an extent that the occupant comes into close contact with the hard base of
      the bed: an important condition to avoid as it is thought to represent an
      aggravated risk factor for pressure ulcers. The authors have developed a
      portable, easy--to use, interactive device that quickly gives accurate
      information as to the condition of a mattress in a clinical setting. The device
      is validated against accelerated fatigue, pressure mapping of bottoming with
      healthy volunteers, and service life of 150 mattresses. The QUINCE SUPPORT SCORE
      provides an objective and valid basis for a mattress replacement programme.

PMID- 11949611
TI  - Selection criteria for systematic literature reviews.

PMID- 11949612
TI  - Lasers in plastic surgery.
AB  - The laser is a relatively new tool in many branches of medicine. In particular,
      in the field of plastic surgery, lasers have found numerous applications. Laser
      light is produced by the stimulated emission of photons from the lasing medium.
      Lasers may be classified according to the lasing medium employed, the wavelength
      of the emitted light and the pulse duration. One of the main uses of lasers is in
      the treatment of vascular lesions such as port wine stain (PWS). The 585 nm
      flashlamp pumped pulsed dye laser (FPPDL) is particularly effective in this role.
      The principle of selective photothermolysis has allowed highly specific targeting
      of different tissue components. Newer lasers have been developed to treat
      pigmented lesions as well as primary and metastatic cutaneous malignancies. In
      cosmetic surgery, lasers have been developed for skin resurfacing and removal of
      wrinkles, tattoos and unwanted hair. There has been recent interest in the use of
      lasers to promote wound healing. Laser therapy is not without complications and
      the safety of both patient and operator must remain paramount. The future is
      likely to hold greater advances in this rapidly developing field.

PMID- 11949613
TI  - Assessing the patient with a skin condition.
AB  - Skin diseases affect 20-30% of the population at any one time, seriously
      interfering with activities in 10%. Skin conditions are, by their vary nature,
      visible. As a result, those with a skin condition receive the same reaction from
      society as anyone who looks 'different'. They can be subjected to stares,
      whispered comments, antagonism, insult or exclusion from normal social activity.
      Those with a skin condition have the needs of all other patients, but in
      addition, the impact upon their lives of a skin condition, its treatment and the
      ways in which others perceive them, makes their situation unique. Many nurses
      however will have little or no experience of patients with skin conditions. They
      need therefore to be aware of the wide-ranging effects skin disease can have on
      the individual and their family. It is important that nurses understand the basic
      principles of skin disease and care, but are also aware of their limitations,
      seeking further advice as necessary. This article will guide the nurse in
      assessing patients with a skin condition.

PMID- 11949614
TI  - A survey of pressure ulcer education within pre-registration radiography courses.
AB  - The prevention of pressure ulcers and the management of people with pressure
      ulcers is multi-disciplinary, though in many places it is considered a nursing
      problem. Radiography environments are a potential cause of pressure ulcers. This
      paper describes the results of a survey of pre-registration radiography education
      institutions regarding the education provision on the prevention of pressure
      ulcers within radiography environments. The survey comprised two parts--a desk
      top review of course prospectuses and a postal questionnaire. Course prospectuses
      for 23 of the 24 institutions were examined for specific mention of prevention
      and management of pressure ulcers but none was found. All 24 institutions in the
      United Kingdom were invited to respond to a questionnaire survey, and 14 replied
      (58% response rate). Responses covered both diagnostic and therapeutic
      radiography programmes. Nine institutions specifically identify teaching on
      pressure ulcers, with the majority of education appearing in year 1 of the
      course, with some courses providing further material later in the programme. The
      survey confirms anecdotal evidence reported in a previous study that
      radiographers have little training in the prevention and management of patients
      at risk of developing pressure ulcers during radiographic procedures. Thirteen
      out of 14 institutions stated that no final year student project had considered
      the prevention and management of pressure ulcers in radiography environments.

PMID- 11949616
TI  - Proceedings of the Symposium on Gastroenteritis Viruses. London, United Kingdom,
      16-18 May 2000.

PMID- 11949615
TI  - The effect of mechanical forces (vibration or external compression) on the dermal
      water content of the upper dermis and epidermis, assessed by high frequency
      ultrasound.
AB  - An ultrasound scanner, is used to detect changes in water content of the upper
      dermis. This has previously been found to vary with age and to show diurnal
      variation. Furthermore, oedema due to venous disease can be shown, using this
      technique, to respond to elevation. In this study, the water content of the upper
      dermis and epidermis of the leg in 16 subjects is increased following vibration
      for 10 minutes using a passive exercise system. A study of pressure applied to
      the skin of the heel for 10 minutes in 14 volunteers also showed an increase in
      water content of epidermis and dermis in young persons, but less so in the
      elderly. It is postulated that the anatomical structure of the vascular bed of
      the upper dermis predisposes to transsudation when pressure to the skin is
      applied, thereby maintaining the resilience of the skin in the young, but less so
      in the elderly.

PMID- 11949617
TI  - Nutrition and Cancer Prevention: New Insights into the Roles of Phytochemicals.
      Washington, DC, USA. September 2-3, 1999. Proceedings and abstracts.

PMID- 11949618
TI  - Insect Toxicology 2000. Proceedings of a meeting. Berkeley, California, USA. 17
      19 July 2000.

PMID- 11949619
TI  - [Handwashing in the hospital, it's vital!].

PMID- 11949620
TI  - Florence Nightingale, Martha Rogers and the art of Feng Shui.

PMID- 11949621
TI  - Position on the role of nurses in the practice of complementary and alternative
      therapies.

PMID- 11949622
TI  - [De gustibus...].

PMID- 11949623
TI  - My brilliant career--health promotion. In development. Interview by Ann Dix.

PMID- 11949625
TI  - Are infantile hemangiomas of placental origin?

PMID- 11949624
TI  - Pathologic features and expression of insulin-like growth factor-2 in
      adrenocortical neoplasms.
AB  - We analyzed a series of adrenocortical neoplasms to compare the clinicopathologic
      features and the expression of insulin-like growth factor-2 (IGF-2) in
      adrenocortical adenomas and carcinomas. IGF-2 is a growth factor commonly
      expressed in many tumors including adrenal cortical and medullary neoplasms.
      Formalin-fixed paraffin-embedded tissues from 64 adrenocortical adenomas and 67
      adrenocortical carcinomas were analyzed. The carcinomas were histologically
      graded from 1 to 4 based on mitotic activity and necrosis. Tumor weight, size,
      and follow-up information were obtained by chart review. Expression of IGF-2 was
      detected by immunohistochemistry with the avidin-biotin-peroxidase complex method
      and a monoclonal antibody against IGF-2. Adrenocortical carcinomas were larger
      (mean: 13.1 cm, 787 g) than adenomas (mean: 4.2 cm, 52 g) (p < 0.001). Inpatients
      with adrenocortical carcinomas, high tumor grade (3 or 4) (p = 0.01) was
      associated with decreased survival. Expression of IGF-2 was higher in
      adrenocortical carcinomas than in adenomas (p < 0.001). These results show that
      tumor size and weight along with expression of IGF-2 protein are useful features
      to assist in distinguishing between adrenocortical adenomas and carcinomas, and
      that high tumor grade is a predictor of survival in adrenocortical carcinomas.
      However, single immunohistochemical markers such as IGF-2 or single
      histopathologic features cannot by themselves separate adrenocortical adenomas
      from carcinomas, and a combination of clinical, gross, and microscopic features
      are needed to establish the diagnosis in difficult cases.

PMID- 11949626
TI  - Historical image: Helmholtz ophthalmoscope, 1851.

PMID- 11949627
TI  - Historical image: Snellen's ophthalmotrobe, c. 1865.

PMID- 11949628
TI  - Measles in bone marrow transplant recipients.

PMID- 11949629
TI  - Treatment options in chronic myelogenous leukemia.

PMID- 11949631
TI  - The common pathways, but different outcomes, of apoptosis induced by
      extracorporeal photopheresis and in vivo chemotherapy may reinforce the important
      immunomodulatory effect of monocytes.

PMID- 11949632
TI  - Multiple myeloma: illegitimate switch recombinations and their relation to
      chromosomal translocations.

PMID- 11949634
TI  - Myelodysplastic syndromes: from French-American-British to World Health
      Organization: a commentary.

PMID- 11949635
TI  - Mutations of Chk2 in primary hematopoietic neoplasms.

PMID- 11949636
TI  - [Care for experience. 6 students of the Freistadt GuKP School visited London via
      the Leonardo da Vinci Project].

PMID- 11949637
TI  - Estimated annual cost of all terrain vehicle-related deaths in West Virginia:
      1990-1999.
AB  - In response to a request from West Virginia lawmakers preparing to introduce
      legislation related to the safe operation of all-terrain vehicles (ATVs),
      estimates were calculated for the economic cost of fatal injuries associated with
      ATV use. Using the reported number of deaths from the U.S. Consumer Product
      Safety Commission and a National Highway Traffic Safety Administration model for
      fatal motor vehicle crashes, a range of cost estimates were calculated for fatal
      ATV-related injuries. The average annual comprehensive economic loss resulting
      from these deaths in West Virginia from 1990 through 1999 was estimated to be
      between $10 million and $34.2 million. Persons killed in ATV crashes in the 1990s
      lost, on average, 43 years of productive life. Due to the fact that non-fatal
      injury data is not collected consistently throughout West Virginia, cost
      estimates for these injuries were not calculated.

PMID- 11949638
TI  - Nurse researchers at the VA Medical Center in Gainesville receive grant funding.

PMID- 11949640
TI  - Lower specificity of occult-blood test on stool collected by digital rectal
      examination.
AB  - BACKGROUND/AIMS: To compare the diagnostic accuracy of an immunochemical fecal
      occult-blood test for colorectal cancer between the stool specimens obtained
      during the routine screening and those during the digital rectal examination.
      METHODOLOGY: One hundred and fourteen patients with colorectal cancer and 228
      healthy controls served as subjects of the study. Fecal occult-blood was tested
      by both of two methods; by the routine screening and by the digital rectal
      examination, and the sensitivity and specificity of an immunochemical fecal
      occult-blood test were determined in these two methods. RESULTS: The sensitivity
      and specificity were 79.8% and 96.5% in the routine screening method, and 86.0%
      and 79.8% in the digital rectal examination method, respectively, showing a
      significant difference in the specificity (P < 0.01) between these two stool
      collection methods. There was no significant difference in the sensitivity
      between these two stool collection methods. CONCLUSIONS: These findings indicate
      that the stool specimens collected at the time of the digital rectal examination
      is not suitable for testing of fecal occult-blood.

PMID- 11949641
TI  - [Detection of Cryptosporidium oocysts in goat kid faeces: comparison of a latex
      agglutination test with three other conventional techniques].
AB  - Detection of Cryptosporidium oocysts from goat kid faeces: comparison of a latex
      agglutination test with three other conventional techniques. A quantitative latex
      agglutination test (QLAT) with monoclonal antibodies for the detection of
      Cryptosporidium oocysts in faeces was compared with 3 other conventional
      techniques: Heine staining on faecal smears (HS) giving semi-quantitative results
      (scores from 1 to 5), sucrose flotation on diluted faeces (SF) with results
      expressed in oocysts/g of faeces (opg), direct ELISA (DE) giving qualitative
      results. Goat kid unconcentrated faecal samples (234) from 8 farms were processed
      according to the 4 techniques. Data were analyzed with Win Episcope 1.0 and
      Testview 1.1 softwares. The oocyst outputs ranged from 100 000 (detection limit
      for SF) to 200 millions opg (mean: 15.2 millions opg). A very good agreement was
      recorded between QLAT and HS, SF, DE: Kappa values ranged between 0.82 and 0.90.
      When considering the samples exhibiting oocysts (or not) as positive (or
      negative) using both HS and SF (n = 219), the sensitivity and specificity of QLAT
      were respectively 95.1 and 96.0%. The lack of sensitivity was observed in faeces
      harboring a few oocysts (< or = 200 000 opg, scores < or = 2) whereas the lack of
      specificity was only observed in 3 samples originating from the same farm. A
      significant correlation was calculated between the percentage of agglutination in
      QLAT and the number of oocysts in SF or scores in HS (Spearman correlation
      ranging from 0.45 to 0.48, p < 0.001). QLAT is a rapid, simple and reliable tool
      for routine detection of Cryptosporidium oocysts in faeces.

PMID- 11949642
TI  - Patient-maintained propofol sedation: a follow up safety study using a modified
      system in volunteers.
AB  - Patient-maintained sedation is a mode of patient-controlled sedation during which
      propofol is administered using a target-controlled infusion, with patient demand
      increasing the target concentration. A system tested previously for safety in our
      institution resulted in oversedation. Aiming to improve safety, we modified the
      system by increasing the lockout period to 4 min,reducing the starting
      concentration to 0.5 microg x ml(-1) and the increments on demand to 0.1 microg x
      ml(-1). As in the previous study, healthy volunteers attempted to render
      themselves unconscious by frequently pressing the demand button. To assess
      effects on memory, volunteers were given keywords to remember every 15 min. The
      maximum target concentration reached varied between 1.0 and 2.5 microg x ml(-1).
      No volunteers lost consciousness, however, one volunteer had a brief period of
      apnoea and oxygen desaturation. The Cp50 for loss of memory for words was 1.26
      microg x ml(-1). Although this version represents an improvement, we conclude
      that the system is not yet completely suitable for use without anaesthetic
      supervision.

PMID- 11949643
TI  - A pilot study of patient-led identification of the midline of the lumbar spine.
AB  - The midline of the lumbar spine is usually identified by palpation of the spinous
      processes. Placement of an epidural or spinal needle is more difficult when these
      bony landmarks are impalpable. This pilot study investigated the ability of 50
      healthy volunteers to identify the midline of their own backs, using light touch
      or proprioception. The midline as identified in this manner was compared with the
      'gold standard' as defined by the interspinous line. Sensation to light touch was
      the most accurate, with 90% of the volunteers able to identify the midline to
      within 6.5 mm. Proprioception using a finger to touch the midline was less
      accurate. This study was carried out on volunteers with palpable spinous
      processes but suggests that, in certain circumstances, a patient-led
      identification of the midline may be of value.

PMID- 11949644
TI  - Postanaesthetic shivering--a new look at tramadol.
AB  - We studied whether tramadol administered at the time of wound closure can prevent
      postanaesthetic shivering. One hundred and fifty patients scheduled for general
      anaesthesia and surgery were randomly allocated and tramadol was administered
      intravenously at a dose of 2 mg.kg(-1) in the high-dose group, 1 mg.kg- in the
      low-dose group and 0.9% saline in the control group. In the high-dose group, 2%
      of patients had postanaesthetic shivering, compared to 4% in the low-dose group
      and 48% in the control group (p < 0.001 vs. tramadol groups). There was no delay
      in tracheal extubation after reversal of neuromuscular blockade. The incidence of
      adverse side-effects such as sedation and vomiting did not differ statistically
      and were clinically not significant. This study strongly supports the use of
      tramadol at wound closure for prevention of postanaesthetic shivering.

PMID- 11949645
TI  - The efficacy of lidocaine administered via the LITA tracheal tube in attenuating
      the extubation response in beta-blocked patients following craniotomy.
AB  - The Laryngotracheal Instillation of Topical Anaesthetic (LITA) tracheal tube has
      an additional pilot tube through which local anaesthetic can be instilled into
      the larynx via 10 small holes above and below the cuff We studied 40 patients
      undergoing supratentorial craniotomy. They were premedicated with two oral doses
      of propranolol 1 mg.kg(-1). The anaesthetic consisted of infusions of
      remifentanil, propofol and vecuronium. On insertion of the first skin clip at the
      end of surgery, 5 ml of either saline or 2% lidocaine was injected into the
      appropriate lumen of the tracheal tube. There was no difference between the
      groups in the degree of coughing or the haemodynamic response to tracheal
      extubation.

PMID- 11949646
TI  - The champagne angle.
AB  - A patient's observation led us to investigate whether drinking from a champagne
      flute required more cranio-cervical extension than drinking from other types of
      wine glasses. We measured the cranio-cervical extension required by normal
      volunteers to drink from four different types of glass. The mean [95% confidence
      intervals] extension from the neutral position required to drain each glass was:
      narrow flute 40 degrees [35-44]; wide flute 22 degrees [19-25]; wine glass 26
      degrees [24-29]; champagne saucer 0 degree [-1-2]. Drinking from the narrow
      rimmed champagne flute required significantly more extension than the other types
      of glass (p < 0.001), and 73% of the total available cranio-cervical extension.

PMID- 11949647
TI  - Training surgeons in critical care.

PMID- 11949648
TI  - Pre-operative optimisation of high risk surgical patients.

PMID- 11949649
TI  - Prolonged pre-operative fluid fasting.

PMID- 11949650
TI  - Colour coding for piped Entonox hoses.

PMID- 11949651
TI  - Survey of airway management equipment in day surgery centres.

PMID- 11949653
TI  - Intubating laryngeal mask use in neck injury patients.

PMID- 11949652
TI  - Intubating laryngeal mask use in neck injury patients.

PMID- 11949654
TI  - Malocclusion testing with the flexible laryngeal mask airway.

PMID- 11949655
TI  - Neurophysiological investigation of neurological complication after regional
      anaesthesia.

PMID- 11949656
TI  - Cement implantation syndrome.

PMID- 11949657
TI  - Eldor needle for combined spinal-epidural anaesthesia.

PMID- 11949658
TI  - Accidental dural procedure and an occluded Tuohy needle.

PMID- 11949659
TI  - Epidural catheter migration.

PMID- 11949660
TI  - National Anaesthesia Day activities.

PMID- 11949661
TI  - [Molecular targeting screening of antineoplastic agents].

PMID- 11949662
TI  - Patellofemoral joint kinetics while squatting with and without an external load.
AB  - STUDY DESIGN: Single-group repeated measures design. OBJECTIVE: To quantify
      patellofemoral joint reaction forces and stress while squatting with and without
      an external load. BACKGROUND: Although squatting exercises in the rehabilitation
      setting are often executed to a relatively shallow depth in order to avoid the
      higher joint forces associated with increased knee flexion, objective criteria
      for ranges of motion have not been established. METHODS AND MEASURES: Fifteen
      healthy adults performed single-repetition squats to 90 degrees of knee flexion
      without an external load and with an external load (35% of the subject's body
      weight [BW]). Anthropometric data, three-dimensional kinematics, and ground
      reaction forces were used to calculate knee extensor moments (inverse dynamics
      approach), while a biomechanical model of the patellofemoral joint was used to
      quantify the patellofemoral joint reaction forces and patellofemoral joint
      stress. Data were analyzed during the eccentric (0-90 degrees) and concentric (90
      0 degrees phases of the squat maneuver. RESULTS: In both conditions, knee
      extensor moments, patellofemoral joint reaction forces, and patellofemoral joint
      stress increased significantly with greater knee flexion angles (P < 0.05). Peak
      patellofemoral joint force and stress was observed at 90 degrees of knee flexion.
      Patellofemoral joint stress at 45 degrees, 60 degrees, 75 degrees, and 90 degrees
      of knee flexion during the eccentric phase, and at 75 degrees and 90 degrees
      during the concentric phase, was significantly greater in the loaded trials
      versus the unloaded trials. CONCLUSION: The data indicate that during squatting,
      patellofemoral joint stress increases as the knee flexion angle increases, and
      that the addition of external resistance further increases patellofemoral joint
      stress. These findings suggest that in order to limit patellofemoral joint stress
      during squatting activities, clinicians should consider limiting terminal joint
      flexion angles and resistance loads.

PMID- 11949663
TI  - The impact of custom semirigid foot orthotics on pain and disability for
      individuals with plantar fasciitis.
AB  - STUDY DESIGN: Single-group, pre-, and postintervention repeated measures design.
      OBJECTIVE: To determine the impact of custom semirigid foot orthotics on pain and
      disability for individuals with plantar fasciitis. BACKGROUND: Few studies have
      examined the efficacy of foot orthotics for plantar fasciitis, and no single
      study has yet examined the effects of semirigid foot orthotics on an established
      quality-of-life instrument. METHODS AND MEASURES: Eight men and 7 women (mean
      ages 44.7 +/- 9.0 years) who reported having plantar fasciitis symptoms for an
      average of 21.3 +/- 23.7 months participated in the study. Subjects were timed
      for a 100-m walk at a self-selected speed, then they rated the pain they
      experienced during the walk using a 10-cm visual analog scale. Subjects also
      completed the pain and disability subsections of the Foot Function Index
      questionnaire. All measures were acquired before the fabrication of custom
      semirigid foot orthotics and 12 to 17 days following onset of foot orthotic use.
      RESULTS: Postorthotic 100-m walk times were not significantly different (t =
      0.39, P = 0.70) than preorthotic values. Postorthotic pain ratings (mean = 0.7 +/
      0.7) for the 100-m walk were significantly less than (Wilcoxon t = 1, P < 0.005)
      preorthotic pain ratings (mean = 3.0 +/- 1.7). Postorthotic Foot Function Index
      pain subsection ratings (Wilcoxon t = 0, P < 0.005) were significantly less than
      preorthotic ratings, demonstrating a 66% reduction in pain ratings. Postorthotic
      Foot Function Index disability subsection ratings (Wilcoxon t = 0, P < 0.005)
      were significantly less than preorthotic ratings, demonstrating a 75% reduction
      in disability ratings. CONCLUSION: Custom semirigid foot orthotics may
      significantly reduce pain experienced during walking and may reduce more global
      measures of pain and disability for patients with chronic plantar fasciitis.

PMID- 11949665
TI  - The effect of lateral ankle sprain on dorsiflexion range of motion, posterior
      talar glide, and joint laxity.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: Assess range of motion, posterior
      talar glide, and residual joint laxity following ankle sprain in a population of
      athletes who have returned to unrestricted activity. BACKGROUND: Lateral ankle
      sprains occur frequently in athletic populations and the reinjury rate may be as
      high as 80%. In an effort to better understand risk factors for reinjury, the
      sequelae to injury in a sample of college athletes were assessed. METHODS AND
      MEASURES: Twelve athletes with a history of lateral ankle sprain within the last
      6 months and who had returned to sport participation were tested. Only athletes
      who reported never injuring the contralateral ankle were included. The injured
      and uninjured ankles of subjects were compared for measures of joint laxity,
      ankle dorsiflexion range of motion, and posterior talar glide. Friedman's test of
      rank order was used to analyze the laxity measures and a MANOVA was used to
      assess the dorsiflexion and posterior talar glide measures. RESULTS: Laxity was
      significantly greater at the talocrural and subtalar joints of the injured
      ankles. There were no significant differences in any of the ankle dorsiflexion
      measurements between injured and uninjured ankles, but posterior talar glide was
      significantly reduced in injured ankles as compared to uninjured ankles.
      CONCLUSION: In our sample of subjects, residual ligamentous laxity was commonly
      found following lateral ankle sprain. Dorsiflexion range of motion was restored
      in the population studied despite evidence of restricted posterior glide of the
      talocrural joint. Although restoration of physiological range of motion was
      achieved, residual joint dysfunction persisted. Further research is warranted to
      elucidate the role of altered arthrokinematics after lateral ankle sprain.

PMID- 11949664
TI  - Electromechanical delay after ACL reconstruction: an innovative method for
      investigating central and peripheral contributions.
AB  - OBJECTIVES: The purpose of this study was to investigate the electromechanical
      properties of atrophied muscle in patients with anterior cruciate ligament (ACL)
      reconstruction and to examine the relationship of changes in these properties for
      a voluntarily elicited maximal isometric contraction and peripherally stimulated
      twitch contraction. BACKGROUND: It is not known if, following ACL reconstruction,
      a prolonged reaction time to a sudden stimulus is due to impaired proprioception
      in the knee joint, a prolonged processing interval in the central nervous system,
      or a greater elasticity in the series elastic component of the quadriceps
      femoris. METHODS: Seventeen patients were recruited 2 to 3 months following a
      unilateral ACL reconstruction. Both the involved leg (ACL-invo group) and the
      uninvolved leg (ACL-uninvo group) were studied. Twenty-two athletes (training
      group) and 18 control subjects (control group) were also tested. These subjects
      performed voluntary maximal isometric contraction (MVC) of the quadriceps
      femoris. Maximal twitch response was also elicited by a supramaximal electrical
      stimulation to the femoral nerve, and surface electromyograms were recorded from
      the vastus lateralis in all four groups. RESULTS: Total reaction time for MVC in
      the ACL-invo group (250.47 ms) was prolonged compared to that of the control and
      training groups. Twitch response in the ACL-invo group (25.26 ms) was prolonged
      compared to that of the other three groups. Premotor time during both MVC and
      twitch response did not differ among the four groups. Electromechanical delay
      during MVC (53.62 ms) and the evoked electromechanical delay in twitch response
      (20.04 ms) were prolonged in the ACL-invo group as compared to the other three
      groups. CONCLUSIONS: Prolonged electromechanical delay in twitch response may be
      due to peripheral physiological disruptions (eg, stiffness of the series elastic
      component, changes of peripheral muscle fiber-type composition, or a decrease in
      function of the excitation-contraction coupling process). A prolonged
      electromechanical delay in twitch response can also explain the prolonged
      electromechanical delay observed for MVC. These findings suggest that prolonged
      total reaction time in MVC, when secondary to a visual stimulus in atrophied
      human quadriceps femoris muscle after ACL reconstruction, may be principally due
      to prolongation of electromechanical delay produced by peripheral physiological
      alterations. However, the contribution of premotor time to prolonged total
      reaction time was not revealed. Our results do not completely eliminate the
      possibility that central nervous system processing time and other neural factors
      are involved in the prolongation of reaction time.

PMID- 11949666
TI  - [Immigration of physicians and dentists into Hungary in the 1980's and 90's].
AB  - Following the fall of the socialist regime in Hungary (1989), it was observed by
      patients and doctors alike that the number of foreign physicians and dentists
      significantly increased in the late 1980's and the early 1990's. There was no
      scientific research so far about these changes. Based on a cross-sectional study
      in 2001, there are 39,122 registered and professionally active members in the
      Hungarian Medical Chamber in Hungary. There are 33,915 physicians and 5,207
      dentists. At present, the total number of foreign citizens among them amounts to
      797, including 517 doctors who studied in Hungarian universities, albeit in
      English, not in Hungarian. There are also 2,167 doctors with Hungarian
      citizenship with a medical diploma from abroad. It is likely, that 260-270 people
      in this group were already Hungarian citizens before entering medical training.
      Subtracting them from the 2,167 doctors and adding 517 foreigners trained in
      Hungary, it may be stated that approximately 2,400 doctors work in the Hungarian
      health care as a result of international migration.

PMID- 11949667
TI  - 2001 Kremers Award address, John Uri Lloyd (1849-1936).

PMID- 11949668
TI  - Selective service and the pharmacist: necessary men in WW II.

PMID- 11949669
TI  - Recharging the battery of life: electricity in the theory and practice of drug
      treatment.

PMID- 11949670
TI  - Pandora's Box or panacea? Using metaphors to create the public representations of
      biotechnology.
AB  - This paper addresses the use of metaphors in creating public representations of
      biotechnology in the United Kingdom's leading quality press. Metaphors referring
      to biotechnology and its applications have been analyzed in press articles
      covering the period 1973-1996. The paper describes how metaphors can be used to
      popularize complex technical information while at the same time providing a
      highly charged message about the technology itself. The analysis draws
      conclusions about the content and general direction of the debate on
      biotechnology during the past three decades.

PMID- 11949671
TI  - Communication challenges for science and religion.
AB  - How can the very different worlds of science and religion communicate
      effectively? Religion requires faith, belief without question. Science demands we
      take nothing on faith, reject any anecdotal evidence. How might these seemingly
      opposed disciplines collaborate to improve public understanding of science and
      impact pending policy making without undermining spiritual well being? Are
      scholars from both disciplines engineering the needed bridges?

PMID- 11949672
TI  - Variations in age-specific homicide death rates: a cohort explanation for charges
      in the age distribution of homicide deaths.
AB  - An age-period-cohort characteristic model previously used to explain age-period
      specific rates of homicide arrests for those 15 to 49 from 1960 to 1995 is
      applied to measures of age-period-specific homicide deaths. The extension of this
      model to the examination of homicide victimization is significant because we are
      able to test the utility of the model across a longer time span (1930 to 1995)
      and a wider range of ages (10 to 79) and disaggregated by sex and race (Whites
      and non-Whites). Although the results indicate that past and recent shifts in age
      period-specific rates of homicide deaths are associated with specific
      characteristics of cohorts, there are some important differences across race and
      sex groupings in the effects of these characteristics. The effects of the cohort
      variables examined in our model are independent of age and period, often
      substantively large, and last throughout the life course. The results are
      consistent with Durkheimian explanations of lethal violence, hypotheses from
      victimization theory, and basic tenets of cohort theory.

PMID- 11949673
TI  - Summer camp, seaside station, and marine laboratory: marine biology and its
      institutional identity.

PMID- 11949674
TI  - Battling breast cancer. [Review of: Lerner, BH. The breast cancer wars: hope,
      fear, and the pursuit of a cure in twentieth-century America. Oxford University
      Press, 2001].

PMID- 11949675
TI  - [Jan Fryderyk Wolfgang's autobiography (1850) in the light of hand-written and
      printed sources].
AB  - The archival collection of the Lithuanian Academy of Sciences in Vilnius (Wilno)
      contains many manuscripts relating to the scientific work of Jan Fryderyk
      Wolfgang (1776-1859), professor of pharmacy and pharmacology of the Wilno
      University in the years 1807-1831, the founder and main figure in the Wilno
      pharmacognostic school, a botanist with substantial achievements in wide-ranging
      research on the flora of the Wilno region, as well as a historian of pharmacy.
      The most interesting of the manuscripts include Wolfgang's Autobiografia
      [Autobiography], written in 1850, and a list of his publications covering a total
      of 57 items (including some that have hitherto remained unknown), a work entitled
      Historya Farmakologii i Farmacyi [History of pharmacology and pharmacy], and a
      particularly valuable manuscript (666 + 12 sheets) entitled Farmakologiia
      [Pharmacology]. Worth mentioning are also two catalogues of books from Wolfgang's
      library: one compiled by Wolfgang himself (37 sheets) and the other by Adam
      Ferdynand Adamowicz. The content of the autobiography manuscript is contained on
      five sheets. The author of the present article analyzes the document, comparing
      the information contained in it with the biographies of J. F. Wolfgang that hhave
      been published so far (these being primarily the biography by Dominik Cezary
      ChodYko, published in 1863, and that by Witold W3odzimierz G3owacki of 1960). The
      text of the autobiography is quoted in full, together with numerous comments. The
      analysis of the manuscript as well as the biographical data contained in the
      above-mentioned biographies indicate that Wolfgang had great achievements as a
      scientist (in both research and organizational work), as a champion of public
      causes and as an educator of a generation of botanists-pharmacognostics. It also
      transpires from the autobiography, as well as from the research by historians,
      that he was a very good and trustful person, who readily granted access to his
      research to his collaborators and pupils. This eventually turned against him: he
      laments the loss of the materials of his floristic research "at untrustworthy
      hands" and deplores the fact that they were published under the name of other
      scientists. Jan Fryderyk Wolfgang died on 17 May 1859, in his estate at Po3uknie.
      He was buried at the no longer extant Lutheran graveyard at Pohulanka. A symbolic
      grave of Wolfgang is to be found at the Rossa Catholic cemetery in Wilno (sector
      XIV, grave no. 157).

PMID- 11949676
TI  - [The Carnegie-Curie scholarships].

PMID- 11949677
TI  - Ethical issues of fetal tissue transplantation: research, procurement, and
      complicity with abortion.

PMID- 11949678
TI  - The primacy of abortion in the moral rhetoric of U.S. Catholic bishops.

PMID- 11949679
TI  - Erasmus Darwin's improved design for steering carriages and cars.
AB  - Carriage journeys in England during the eighteenth century were notoriously
      dangerous. Rutted and pot-holed roads exacerbated the deficiencies in steering,
      springing and stability. In 1758 the young Dr. Erasmus Darwin (1731-1802; F. R.
      S. 1761) was travelling about 10,000 miles a year in visits to patients from his
      house at Lichfield. To alleviate the danger and discomfort of his journey, he
      developed a design for improved carriage steering and stability, which he road
      tested over 20,000 miles on two carriages. In 1765 Richard Lovell Edgeworth (1744
      1817; F. R. S. 1718) heard about Darwin's design, urged the Society of Arts to
      enquire about it, and then visited Darwin himself. With the aid of manuscripts
      from the Archive of the Royal Society of Arts and elsewhere, I offer a
      reconstruction of Darwin's improved method of steering, which relies on four
      jointed rods, initially in the form of an isosceles trapezium. The mechanism was
      reinvented more than 50 years later, and came to be used widely in early modern
      cars.

PMID- 11949680
TI  - Calibration of the paediatric index of mortality score for UK paediatric
      intensive care.

PMID- 11949682
TI  - The effects of positive acceleration on the central nervous system.
AB  - The effects of positive acceleration on the CNS were studied by applying negative
      pressure to the lower body (LBNP) of unanesthetized rabbits. The LBNP which can
      simulate well the effects of positive acceleration induced high voltage slow
      bursts with amplitude 600-800 microV and frequency of 2-3 Hz in the EEG of the
      rabbits, which seemed to be quite similar to those observed by Adey et al. in the
      EEG of the centrifuged monkeys and cats. Because the physiological effects of
      LBNP as well as positive acceleration had been greatly attributed to disturbance
      of circulation in the CNS, much effort was made in this experiment to study the
      mechanisms triggering the slow bursts especially in relation to changes in
      hemodynamic cardiovascular measurements. By LBNP, both blood pressure and blood
      flow fell markedly and cerebral circulation was obstructed, but these changes
      were recovered to some extent approximately 10 seconds after the application of
      LBNP. These changes fell again until the release of LBNP, when cerebral blood
      flow was profoundly increased. The slow bursts seemed to be induced only in such
      periods when cerebral blood flow was profoundly increased after a failure of
      cardiovascular compensatory mechanisms such as a decrease of heart rate with
      irregular cardiac rhythm had occurred by repeated application of a greater LBNP.
      These results suggest that the necessary important change inducing the slow
      bursts is a sudden rush of blood to the anoxic CNS and is not only an anoxic
      condition of the CNS during LBNP, and the bursts may possibly be triggered by
      mechanical distortion of the neuronal network by a sudden fluid movement within
      the anoxic brain or change in permeability of blood vessels and the glial cells
      which might greatly modulate neuronal excitability by such sudden return of blood
      to the anoxic CNS.

PMID- 11949681
TI  - The effects of high intensity visible and ultraviolet light on the death of
      microorganisms.
AB  - The expectation that microorganisms would be exposed to very high visible light
      intensity in a space environment led to the investigation of the killing of
      microorganisms by visible light. The carotenoid-containing yeast Rhodotorula
      glutinis was one of the several organisms investigated. It was found that despite
      the carotenoid content of the organism it can be killed by endogenous
      photosensitized oxidation. While the effects of various parameters such as
      culture age, temperature, etc., were studied, particular emphasis was placed upon
      the development of action spectrum, determination of sites of action and the
      mechanism by which cells are killed. The portion of the spectrum responsible for
      lethality lies between 300 and 400 nm with an apparent maximum response around
      390 nm. The nucleus appeared to be damaged, as evidenced by a mutagenic effect
      when cells were radiated with light above 300 nm. Previously the only reported
      mutagenic responses from light of these wavelengths have been noted when cells
      have been irradiated in the presence of added sensitizing dyes. Increased leakage
      of irradiated cells indicated permeability membranes have undergone damage.
      Overall respiration of the cells is also decreased at a rate corresponding to the
      loss in viability. Such random damage to cells indicates that whatever the
      damaging species is, it must be quite non-specific. The sensitizing agent could
      be a free radical and evidence has been developed to support such a proposal. The
      sulfhydryl-containing compounds cysteine and gluthathione are capable of
      protecting the cells from death. Since these compounds are known to protect the
      organisms from ionizing radiation by the trapping of free radicals, it is logical
      to presume that the damaging species is a free radical. Little or no protection
      is offered to the microorganism by fat-soluble antioxidants such as tocopherol
      and related species. This would indicate that the primary lethal site must be in
      the water phase. It is likely that dehydration of the cells such as could be
      expected in a spacial environment would initially increase their susceptibility
      to irradiation, but upon intense dehydration could also result in their increased
      resistance.

PMID- 11949683
TI  - Photosensitizing effect of cations on amino acids and peptides.
AB  - In connection with a study of the chemical evolution of abiogenically synthesized
      organic compounds on primitive Earth and the physical conditions of other
      planets, this paper reports the experimental results obtained by the photolysis
      of solutions of aliphatic amino acids (glycine, alanine, valine, leucine, n.
      leucine) and peptides in the atmosphere of the air, N2, Ar and CO2 in the
      presence of the most simple photocatalyzers-cations of sulphates. The evidence
      shows that the photochemical conversion of NH2 acids depends on the content of
      the atmosphere. The decay of NH2-group is most active in air. N2 and Ar exert no
      significant influence on deamination, whereas in the atmosphere of CO2 the
      formation of ammonia in valine, for example, was only 29 per cent of its total
      amount during photolysis in the air. Cu2+ and Fe2+ catalyzed while Al3+ inhibited
      the ammonia excretion. The formation of acetaldehyde during alanine photolysis
      was actually independent from the atmosphere of N2 and was inhibited in Ar and
      CO2. Oxydative processes inducing the formation of glyoxalic acid and
      formaldehyde were sharply inhibited in Ar, N2 and CO2. Under the influence of
      ultraviolet light of the decay of NH2-acids is also accompanied by the formation
      of new NH2-acids. The photosensitizing effect of cations induces a rupture of -CO
      NH-bonds in peptides and, provided heavy radiation doses, prevents the formation
      of new NH2-acids. The longer the dipeptide chain, the more significant the
      quantum yield of its decomposition. The photolysis of dipeptides, leading to
      their decay, does not necessarily induce a hydrolytic rupture of -CO-NH-bonds
      resulting in the formation of three amino acids. The results obtained permit
      approaching problems concerning the effect of the gas content of the atmosphere
      and various cations (photocatalyzers) on photolytic conversion of abiogenically
      synthesized and biogenically significant substances, amino acids for example, at
      the action of ultraviolet light.

PMID- 11949684
TI  - Resistance of the protozoan Colpoda maupasi to Martian conditions of atmospheric
      pressure and low partial pressure of oxygen.
AB  - Among the most important factors limiting the active life of animal organisms in
      Martian conditions are low atmospheric pressure and insignificant amounts of
      oxygen in the atmosphere (no more than 0.15% of the Earth's atmosphere). The
      experiments with aerobic protozoon C. maupasi have shown that in conditions of
      hermetically sealed chambers, for instance in 2.5 liter anaerostats, the
      protozoon can survive for a long time and reproduce in an atmosphere of air or
      nitrogen containing 1 or 0.0005% oxygen at a pressure from 15 mm Hg and higher.
      At the atmospheric pressure 10 mm Hg we observed a considerable decrease in the
      survival percentage and no reproduction. The exposure to 5 mm Hg resulted in a
      100 per cent mortality of the protozoon. In a specially-constructed chamber
      "Photostat", in which current atmosphere pressure were automatically maintained
      during an experiment of many days, the reaction of the infusoria was somewhat
      different: they reproduced and existed not only at the pressure of 10-15 mm Hg,
      but also at 5 mm Hg, in an atmosphere of both air and nitrogen containing from 1
      to 0.0005% O2. This indicates not only low-oxygen consumption of unicellular
      animals but also the capability of cells to extract some traces of this gas from
      the atmosphere. Low pressure and some traces of oxygen in the Martian atmosphere
      are not an impediment for the existence of some of the Earth's animals, such as
      the protozoon C. maupasi for example.

PMID- 11949685
TI  - Characteristics of biological effects of cosmic radiation, model investigations.
AB  - In view of the probability of the influence of ionizing radiation on crewmen and
      the appropriate problem of creating adequate anti-radiation protection, it is
      necessary to investigate the peculiarities of biological effects of cosmic
      radiation. Under actual space flight conditions, cosmic radiation will affect the
      human organism in the complex along with other factors. Full imitation of cosmic
      radiation on the ground is impossible but it can exert influence on the human
      radiosensibilty. In this connection, the successful solution of the problem of
      obtaining appropriate information can be made by a reasonable combination of both
      ground radiobiological and medical-hygienic investigations and those carried out
      by using artificial earth satellites. The available experience in carrying out
      such research and its results are given in this report. Information on
      investigating the peculiarities of biological effects of protons in the wide
      spectrum of energy is also included. The report contains the data of observing
      immediate and later effects of radiation influence on higher animals and also on
      many biological objects arranged in various levels of evolution and biological
      organizations. The values of the RBE for protons are given.

PMID- 11949686
TI  - Vestibular analyzer as a critical organ in the evaluation of radiation hazards
      during space flights.
AB  - During space flights the vestibular analyzer functions under conditions which are
      not usual for Earth environments. The vestibular analyzer periodically or
      constantly experiences the action of angular, linear or Coriolis acceleration
      combined with ionizing radiation. The quantitative evaluation of the functional
      state of the vestibular analyzer made it possible to obtain material on
      semicircular canal activity disturbances at different periods of radiation
      sickness and responses of the irradiated body, given various doses of gamma
      radiation, to angular and Coriolis acceleration. Experiments were performed on
      250 rabbits and 22 dogs. Rabbits were exposed to the total gamma radiation at
      doses of 50, 100, 500, 800, 5000, 10000 rad; dogs experienced single and
      fractional radiation exposures at doses of 200 rad (gamma-rays) and at doses of
      500 and 350 rad (protons of 510 MeV). Specific conditions under which the
      astronaut's vestibular analyzer is functioning during space missions and our own
      experimental results make it possible to state that the vestibular analyzer
      serves as the critical organ in evaluation of radiation hazards during space
      flights.

PMID- 11949687
TI  - Biosatellite II mission.
AB  - Biosatellite B was launched from Cape Kennedy, Florida, on a two-stage DELTA
      launch vehicle at 6:04 p.m. on 7 September, 1967. Approximately nine minutes
      later the 435 kg spacecraft biological laboratory was placed into a satisfactory
      315 km near-circular earth orbit, successfully separated from the launch
      vehicle's second stage and was designated Biosatellite II. The scientific payload
      consisting of thirteen selected general biology and radiation experiments were
      subjected to planned, carefully controlled environmental conditions during 45
      hours of earth-orbital flight. The decision was made to abbreviate the scheduled
      3-day mission by approximately one day because of a threatening tropical storm in
      the recovery area, and a problem of communication with the spacecraft from the
      tracking stations. Highest priority was placed on recovery which was essential to
      obtain the scientific results on all the experiments. The operational phase of
      the mission came to a successful conclusion with the deorbit of the recovery
      capsule, deployment of the parachute system and air recovery by the United States
      Air Force. The 127 kg recovery capsule was returned to biology laboratories at
      Hickam Air Force Base, Hawaii, for disassembly and immediate inspection and
      analysis of the biological materials by the experimenters. It was evident
      immediately that the quality of the biology was excellent and this fact gave
      promise of a high return of scientific data. The environmental conditions
      provided to the experimental material in the spacecraft, provisions for
      experimental controls, and operational considerations are presented as they
      relate to interpretation of the experimental results.

PMID- 11949688
TI  - Effects of radiation during space flight on microorganisms and plants on the
      Biosatellite II and Gemini XI Missions.
AB  - The results of recent experiments with the lysogenic bacteria, Escherichia coli
      and Salmonella typhimurium, the bread mold Neurospora crassa and the flowering
      plant Tradescantia on the Biosatellite II and Gemini XI Missions will be
      summarized. In the lysogenic bacteria experiment (Dr. Rudolf H.T. Mattoni, NUS
      Corporation) on the Biosatellite II mission significant effects of space flight
      were found on both growth rate and the induction of prophage. In that part of the
      Neurospora experiment on both the Biosatellite II and Gemini XI Missions (Dr.
      J.F. de Serres), utilizing non-dividing and inactive spores, no difference was
      found in the genetic effects of radiation between the flight and ground samples.
      In that portion of the Neurospora experiment on the Gemini XI mission utilizing
      rapidly-metabolizing spores the genetic effects of radiation were less serious in
      the flight samples than the ground samples. In the Tradescantia experiment (Dr.
      A.H. Sparrow, Brookhaven National Laboratory) on the Biosatellite II Mission, the
      irradiated flight material, in general, produced increased rates of cell death,
      abortion of pollen, loss of reproductive integrity, as well as other
      abnormalities in cell structure and function. In some of the experiments there
      were found significantly genetic effects of space flight alone, and the
      enhancement of various genetic effects of radiation under weightlessness was no
      more than 2- or 3-fold.

PMID- 11949689
TI  - Mutational responses of insects in the Biosatellite II experiment.
AB  - Genetic effects associated with space flight include mutation induction by the
      space flight itself, and enhancements or antagonisms of radiation-induced
      mutations. The conditions of space flight vary in mutagenic effectiveness from no
      response at all to responses nine times that found in ground-based controls. The
      test systems follow the sensitivity pattern: spermatogonial translocations >
      oogonial and oocyte nondisjunction > recessive lethality of stages in
      spermatogenesis > dominant lethality of stages in spermatogenesis. Large
      enhancing and antagonistic effects of space flight in conjunction with radiation
      were observed in the Biosatellite II experiment. The most surprising one was the
      elimination of the effect of 2500 R by space flight in Habrobracon oogonia where
      the effects of 500 R normally can be easily observed. Two sets of parameters are
      considered in attempts to explain the responses: (1) the nature of the biological
      targets, and (2) the particular conditions of space flight that are responsible
      for the effects.

PMID- 11949690
TI  - Biosatellite II--physiological and somatic effects on insects.
AB  - Interesting physiological and somatic effects of space flight have been observed
      in a variety of insects on board Biosatellite II. Wasps, beetles and fruit flies
      have demonstrated positive effects of the space flight alone or in combination
      with irradiation. In the flour beetle, Tribolium confusum, the incidence of a
      developmental wing abnormality was measured. This abnormality, which mimics the
      mutation known as "split", was significantly increased in beetles which were
      flown as young pupae, pre-irradiated with X rays to bring them into their
      sensitive dose range and gamma irradiated during flight. Wing abnormalities
      increased from a ground value of 29.9 per cent to a value of 44.8 per cent. The
      length of the pupal period was also measured. Although there was a significant
      increase of the flight pupal period over that of the ground control, the most
      likely explanation seems to be the temperature drop of the flight samples between
      separation and retrieval of the flight capsule. In the parasitic wasp,
      Habrobracon juglandis, flown in the adult stage, several interesting results have
      been obtained in terms of reproductive performance, life span and enzyme
      activity. Reproductive performance, measured by the average number of eggs
      laid/female/day, was unaffected by flight for control unirradiated wasps.
      However, for females X rayed with 2000 R prior to flight, the characteristic
      depression of egg-laying at 10 days post-irradiation was negligible in the flight
      animals. A more pronounced effect was observed in those females which received
      the chronic 2667 R gamma ray dose in flight; egg production actually
      progressively increased to twice the level of the ground sample. It was observed
      that males were disoriented in their mating behavior for 2 days after the flight.
      When the dose level data was pooled, the life span of females was found to be
      significantly longer in the flight group. Upon analysis of the activity of the
      enzyme, xanthine dehydrogenase (XDH), adult flight males were found to have a
      significantly decreased XDH activity compared with ground controls. No
      significant difference was found between female F1 progeny of flight and ground
      males. XDH activity was also analyzed in F1 progeny of Drosophila melanogaster,
      orbited as adults and larvae. For the F1 male progeny of adult males, there was a
      significantly depressed average XDH activity compared with ground controls for
      the highest irradiation dose. For F1 male progeny of flight larvae, there was a
      statistically decrease of XDH activity only between the off-spring of irradiated
      flight and ground larvae. Further somatic changes were observed in Drosophila
      larvae, in which chromosome aberrations were studied.

PMID- 11949691
TI  - Weightlessness experiments on Biosatellite II.
AB  - Four experiments in the aft compartment of Biosatellite II investigated the broad
      question of the effect of nearly zero gravity on the development, morphology and
      metabolism of plants and animals. The fertilization and development of the egg of
      a vertebrate (the frog, Rana pipiens), the feeding and growth of a protozoan (the
      giant amoeba, Pelomyxa carolinensis), the orientation of leaves and petioles of a
      young dicotyledon (pepper plants, Capsicum annuum) and the morphogenesis,
      orientation, histochemistry and biochemistry of a monocotyledon seedling (wheat,
      Triticum vulgare) gave a broad scope. All are known to have specific responses to
      normal gravity and changes in them might be expected to reflect the effects of
      orbital flight on living organisms. No differences in development of the frog
      eggs could be detected. Unfortunately, the 3 1/2 hour delay in launch allowed the
      first cleavage (the stage most sensitive to inversion) to appear before launch.
      Although the orbited embryos were somewhat slower to reach certain stages of
      development, recovered embryos developed just as did the controls. The amoebae
      fed normally while in orbit, and specimens fixed in orbit retained the ordinary
      heteropodal shape. Growth rates of orbited amoebae, both fed and starved, were
      slower than controls following reentry and recovery procedures. In continuous-fed
      organisms there was little or no effect of flight detectable in growth rate or
      actual number of divisions. Electron micrographs showed no abnormalities and few
      differences between flight and control organisms. The pepper plants were
      photographed in orbit at ten-minute intervals, as were the clinostat and erect
      controls. The subsequent measurement of photographs showed that in the orbited
      plants all leaves showed epinasty, the interaxial angle decreasing by 20-60
      degrees C. Plants on the horizontal clinostat behaved comparably, but recovered
      more rapidly than orbited plants when returned to the normal erect position.
      Although the maximum age of wheat seedlings was only 65 hours, coleoptile and
      root growth rates during that time had not been significantly altered by flight
      or by slow rotation on a horizontal clinostat. There was some evidence that
      growth was accelerated after normal gravity was restored. The orientation of
      coleoptiles and of primary and lateral roots of orbited plants varied
      significantly from the normal erect seedlings but was almost identical with that
      of clinostat plants. The Periodic-Acid-Schiff technique on sectioned material
      showed starch grains at the bottom of cells of erect control coleoptile and root
      tips, while in orbited and clinostated plants the grains were located more or
      less at random. Histochemical differences between clinostat and orbited tissues
      are apparent however. Peroxidase localization varied and its activity was higher
      in both clinostat and orbited tissues; five other enzymes studied biochemically
      showed no differences. These experiments all suggest that there is no deleterious
      effect on living organisms or their activities from short-term weightlessness.
      Several results indicate that the horizontal clinostat may simulate the
      weightless state effectively here on Earth.

PMID- 11949692
TI  - Life sciences and space research VII: proceedings of the Open Meeting of Working
      Group V at the Eleventh Plenary Meeting of COSPAR, Tokyo, 14-16 May 1968 and The
      Symposium on Biological Effects of Radiation in Space, Tokyo, 10 May 1968.

PMID- 11949693
TI  - [Public health facilities, international modernization and cooperation.
      Venezuela's National Nursing School Project, 1936-1950].
AB  - In the end of the 19th century, the Venezuelan public health system was in the
      hands of religious women who ran the public health facilities. A new educational
      model would produce professional nurses who came to raise the standards of their
      occupation. Undoubtedly, this objective could not be properly met due to the
      candidates' low educational level and the need of a health service that searched
      for more economical means to face its demands with trained personnel but without
      real educational improvements. Another hindrance was the resistance of
      traditional medicine, which prevented a view of health as a whole, which
      comprehends social and preventive aspects. It was rather difficult for the
      founders of nursing schools to make public health facilities develop health
      orientation.

PMID- 11949694
TI  - [Medical schools in Sao Paulo and the creation of Escola Paulista de Medicina].
AB  - The present article analyzes the foundation of Escola Paulista de medicina (EPM)
      by discussing the role played by health sciences in the development of Sao
      Paulo's society, mainly in the 1930's. The participants in the project intended
      to meet the demands for universities and medical assistance by defending
      specialized knowledge and scientific competence as the base for social
      development through science, education and health. EPM was gradually created with
      the participation of non-academic agents and institutions that were important for
      the institution official and social recognition and permanence. Thus, in the
      beginning of the 1940's, it was decisive to build a hospital for the school-
      Hospital Sao Paulo. This article also intends to contribute to the understanding
      of the functions science has in social organization while dealing with the
      constituting processes of the specific medical field.

PMID- 11949695
TI  - [Contribution of post-normal science to public health and the issue of social
      vulnerability].
AB  - The objective of this article is to discuss the threats to public health, by
      taking into consideration the arguments of Funtowicz et al. (1997, 1994) about
      issues related to the complexity and uncertainties of the studies, evaluation and
      management of the threats to public health that have been observed in the
      relationship between public health and the vulnerability of social groups. The
      prevailing discourse on public health uses statistical data, which reduce illness
      to a biologically determined case relation, do not take into account the history
      of society and holds individuals responsible for their health conditions. We
      intend to show that, as a dynamic process, health requires a new approach to
      consider these issues. Socially-excluded groups have weak capacity to react and,
      maybe due to it, they are more likely to get sick. Consequently, discussing the
      complexity of the studies, evaluation and management of threats to public health
      would avoid any type of reductionism or determinism.

PMID- 11949696
TI  - [A short history of evolutionary theory].
AB  - The history of the Theory of Evolution has been told a number of times by
      historians, philosophers, professors, writers, scientists and so on. However,
      many of these versions differ from or even contradict one another. In this
      article, the history of the Theory of Evolution is retold according to a
      dialectical-materialistic perspective. It analyzes the historical contradictions
      between Darwinian evolution theory and Mendel's model, the background that led to
      the synthetic theory of evolution, the debate carried out by classic schools and
      the result of synthesis, as well as the still current debate between Neutralism
      and Selectionism. Finally, it also discusses the interpretative model used ("an
      idiosyncratic dialectic materialism"), mainly in relation with Popper's and
      Kuhn's models.

PMID- 11949698
TI  - Inconspicuous consumption.
AB  - The 1990s were a decade of less flash and more cash for life's big and little
      necessities. Tracking the Consumer Expenditure Survey reveals how our shifting
      tastes and changing demographics are transforming the way we spend.

PMID- 11949699
TI  - What seems to be the problem?
AB  - Psychotherapy has lost some of its stigma since Sept. 11, but many Americans
      still have issues with seeing a shrink.

PMID- 11949700
TI  - Cancer prevention and control initiatives.

PMID- 11949701
TI  - Sex education.

PMID- 11949702
TI  - The circuitous journey to the Patients' Bill of Rights: winners and losers.

PMID- 11949703
TI  - The ethics of middle-class access to legal services and what we can learn from
      the medical profession's shift to a corporate paradigm.

PMID- 11949704
TI  - Do neuropsychological tests detect preclinical Alzheimer's disease: individual
      test versus cognitive-discrepancy score analyses.
AB  - Attempts to identify cognitive markers of a preclinical phase of Alzheimer's
      disease (AD) have yielded inconsistent findings. The problem may stem in part
      from methodologies that are insensitive to potential subgroups within the at
      risk, preclinical AD population (PCAD). The present study investigated the
      utility of asymmetric cognitive profiles in identifying individuals at risk for
      AD. Twenty elderly adults who were later diagnosed with AD (PCAD) and 20 matched
      control participants were compared on measures of cognitive asymmetry derived
      from difference scores on tests of verbal and visuospatial ability. Although both
      groups performed similarly on the individual tests, comparisons using difference
      scores revealed significantly larger discrepancies between naming and
      visuoconstruction skills in the PCAD group. The PCAD group also had a higher
      frequency of asymmetric cognitive profiles relative to a normative group.

PMID- 11949705
TI  - Priming of two-dimensional visual motion is reduced in older adults.
AB  - Previously, Y. Jiang, P. Greenwood, and R. Parasuraman (1999) reported that
      priming of rotating three-dimensional visual objects is age sensitive. The
      current study investigated whether there is also an age-related difference in
      priming with simple two-dimensional (2-D) moving stimuli (i.e., whether a prime
      stimulus moving in a particular direction causes a subsequent ambiguous target
      stimulus to be seen moving in the same direction as the prime). In 2 experiments,
      younger and older adults judged the directions of moving sine-wave gratings.
      Groups differed neither in determining the direction of a single 2-D movement nor
      in detecting motion reversals in successively moving gratings. However, the older
      group showed a significant reduction in the extent of 2-D motion priming. The
      decrement in older adults for visual motion priming may reflect age-related
      changes in temporal processing in human visual cortex.

PMID- 11949706
TI  - Object recognition and object orientation in Alzheimer's disease.
AB  - There are a wide variety of neuropsychological deficits in Alzheimer's disease
      (AD), among which are disorders of visual perception and spatial cognition. The
      present study investigated the ability of 20 mildly to moderately deteriorated
      patients with AD (and 174 age- and education-matched controls) on tasks that
      required them to visually identify, provide the canonical orientation of, and
      mentally rotate common objects. Some 85% of the AD patients performed poorly on
      all tasks. The authors were able to identify a small number of individual
      patients whose pattern of performance represented double dissociations between
      recognizing objects and knowing their canonical orientation. These findings are
      interpreted in the context of previous findings, especially as to whether
      information relating to an object's orientation and identity is independently
      coded.

PMID- 11949707
TI  - Contribution of specific cognitive processes to executive functioning in an aging
      population.
AB  - The current study investigated executive function measures emphasizing Alpha Span
      (ASp) to understand relationships among executive and nonexecutive tasks.
      Nondemented older participants (N = 417) received a comprehensive cognitive
      battery. Age and vocabulary adjusted correlations revealed associations among
      ASp, Wechsler Adult Intelligence Scale--Revised (D. Wechsler, 1981) Digit Span
      subtests, and fluency tasks. Principal-components analysis with varimax rotation
      revealed a 4 component solution (86.4% of the variance) with executive variables
      contributing to all loadings. Calculated component indices were submitted to a
      regression analysis predicting ASp performance. After accounting for age (6.3% of
      the variance), Component 3 reflecting brief attention-mental manipulation
      accounted for 13.4% of ASp variance; Component 1, verbal language ability, 11.5%;
      Component 2, sustained attention-mental tracking, 1.9%; and Component 4,
      visuoperceptual spatial organization-planning, 0.9%. Results stress the
      importance of considering executive and nonexecutive aspects of cognition when
      conceptualizing executive functioning.

PMID- 11949708
TI  - False recognition of pictures versus words in Alzheimer's disease: the
      distinctiveness heuristic.
AB  - False recognition of semantic associates can be reduced when older adults also
      study pictures representing each associate. D. L. Schacter, L. Israel, and C.
      Racine (1999) attributed this reduction to the operation of a distinctiveness
      heuristic: a response mode in which participants demand access to detailed
      recollections to support a positive recognition decision. The authors examined
      patients with probable Alzheimer's disease (AD) and older adults with this
      paradigm. Half of the participants studied pictures and auditory words; the other
      half studied visual and auditory words. Older adults who studied pictures were
      able to reduce their false alarms compared with those who studied words only. AD
      patients who studied pictures were unable to reduce their false alarms compared
      with those who studied words only and, in fact, exhibited trends toward greater
      false recognition. Implications for understanding semantic memory in AD patients
      are discussed.

PMID- 11949709
TI  - Information processing speed and sentence comprehension in Parkinson's disease.
AB  - This study tests the hypothesis that sentence comprehension difficulty in
      Parkinson's disease (PD) is related in part to altered information processing
      speed that plays a crucial role in grammatical processing. The authors measured
      information processing speed in 32 PD patients without dementia using a lexical
      list-priming paradigm in which the interstimulus interval (ISI) between the prime
      and the target varied. Sentence comprehension accuracy was also assessed in 22 of
      these patients. Sentence comprehension accuracy for object-relative center
      embedded sentences was impaired in a subgroup of PD patients. This subgroup of PD
      patients primed at an abnormally long ISI. Similarly, only PD patients who primed
      at a long ISI had greater difficulty understanding sentences with an object
      relative clause than a subject-relative clause. Findings suggest that slowed
      information processing speed contributes to sentence comprehension difficulty in
      PD.

PMID- 11949710
TI  - Prefrontal contributions to delayed spatial and object alternation: a positron
      emission tomography study.
AB  - Delayed alternation tasks are frequently used as probes of frontal lobe
      functioning. To clarify the neural substrates of delayed alternation performance
      in humans, the authors measured regional cerebral blood flow with H2(15)O
      positron emission tomography in healthy subjects as they performed delayed
      spatial and object alternation. Consistent with the monkey lesion literature,
      increased dorsolateral prefrontal activity emerged during delayed spatial
      alternation but not delayed object alternation, whereas orbitofrontal activations
      emerged in both alternation tasks. The possible cognitive processes contributing
      to the orbitofrontal and dorsolateral prefrontal involvement in delayed
      alternation are discussed. Additional activations localized to several nonfrontal
      regions suggest caution in interpreting alternation deficits in patients as
      strictly reflecting frontal lobe impairment.

PMID- 11949711
TI  - Memory encoding and retrieval in frontotemporal dementia and Alzheimer's disease.
AB  - Memory encoding and retrieval strategies were assessed in patients with behavior
      executive variant frontotemporal dementia (FTD), language variant FTD, and
      Alzheimer's disease (AD) using verbal and visuospatial supraspan learning tests.
      FTD patients obtained higher free recall, cued recall, and recognition scores
      than AD patients. Comparison of free recall scores with cued recall and
      recognition scores was similar in the 3 dementia groups. Groups did not differ in
      semantic clustering strategies during learning, but serial-order recall was more
      common in FTD patients. These data do not support the idea that FTD patients'
      poor memory is due to a selective retrieval disorder, though FTD patients may
      fail to implement sophisticated organizational strategies during learning. FTD
      patients' retained capacity for encoding new information into long-term
      declarative memory is likely due to relatively spared medial temporal lobe
      involvement.

PMID- 11949712
TI  - Evidence for intact semantic representations in patients with frontal lobe
      lesions.
AB  - Patients with frontal lobe lesions and control participants were assessed on 2
      tests of semantic knowledge. In the triadic comparison task, participants were
      shown all possible triplets of 12 animal names and judged which 2 of each triplet
      were most alike. In the ordered similarity task, participants rank ordered
      animals in terms of their similarity to a target animal. For both tasks, semantic
      structure--derived from multidimensional scaling techniques--revealed similar
      representations in patients with frontal lobe lesions and control participants.
      Additional pathfinder analyses also produced networks that did not differ between
      groups. These patients exhibited intact semantic knowledge despite deficits on
      tests of free recall and verbal fluency that involved the same semantic category
      and exemplars. Thus, intact representation of semantic knowledge in frontal
      patients stands in contrast to their marked deficits in strategic retrieval of
      semantic knowledge.

PMID- 11949713
TI  - Cognitive performance in very old diabetic persons: the impact of semantic
      structure, preclinical dementia, and impending death.
AB  - The authors examined the associations of diabetes mellitus with cognitive
      performance in a population-based sample of nondemented and nondepressed very old
      persons. Diabetic participants (n = 31) were compared with nondiabetic controls
      (n = 307), adjusting for age, educational level, and related vascular diseases
      and signs. Results showed that diabetic persons performed significantly worse on
      tests of verbal fluency and episodic memory but that the effects on both types of
      abilities were less pronounced in tasks involving higher degrees of semantic
      structure. Follow-up analyses further revealed that preclinical dementia and
      impending death accounted for much of the observed associations. The results
      suggest that cognitive deficits among very old diabetics are most likely detected
      by tasks that draw less on semantic structures and that the most robust effects
      may be found in letter fluency performance.

PMID- 11949714
TI  - Interhemispheric stroop-like interference in number comparison: evidence for
      strong interhemispheric integration of semantic number information.
AB  - Three experiments investigated interhemispheric interactions in number comparison
      using the interhemispheric Stroop-like paradigm (E. Ratinckx, M. Brysbaert, & B.
      Reynvoet, 2001). In all experiments, a target was presented in I visual field
      simultaneously with a distractor in the other visual field. In Experiment 1, both
      target and distractor were of the same modality (Arabic digits), whereas in
      Experiment 2, target and distractor were of different modalities (Arabic digits
      and word numerals). In Experiment 3, the interhemispheric Stroop-like task of
      Experiment 1 was combined with intrahemispheric conditions to evaluate the
      strength of the interhemispheric interactions. Overall, the results point to
      strong interhemispheric integration during semantic access and response
      preparation with very weak lateralization of the semantic number system.

PMID- 11949715
TI  - Negative priming in patients with Parkinson's disease: evidence for a role of the
      striatum in inhibitory attentional processes.
AB  - Patients with Parkinson's disease (PD) and normal controls (NCs) performed a
      negative priming task. NCs displayed the normal pattern of negative priming in
      that relative to a control condition they were slower to identify a target within
      a stimulus array when it had been a distractor in the previous array. PD patients
      did not display any evidence of negative priming. In contrast, both PD patients
      and NCs displayed statistically the same level of spatial priming and response
      repetition cost. Regression analyses indicated that although symptom severity,
      symptom characteristics, and global cognitive functioning were not reliable
      predictors of negative priming or spatial priming in PD patients, greater symptom
      severity and poorer global cognitive functioning were associated with less
      response repetition cost. The possible role of the striatum in negative priming,
      spatial priming, and response repetition cost is discussed.

PMID- 11949716
TI  - Enhanced negative priming in Parkinson's disease.
AB  - In the ignored repetition paradigm, negative priming (NP) is defined as the
      increase in response time that occurs when the current target stimulus served as
      a distractor stimulus in the previous trial. In this study, 25 Parkinson's
      disease (PD) participants and 17 age-matched healthy controls (HCs) were tested
      using a touchscreen version of the ignored repetition task that allowed response
      time to be partitioned into response initiation and response execution segments.
      In both groups, NP effects were stronger in the response execution than in the
      response initiation segments. The most striking result was that the PD group
      showed larger NP effects overall than the HC group. In PD, clinical ratings of
      bradykinesia, but not tremor, were related to larger NP effects. Results indicate
      that in PD, disruption of dopamine neuromodulation diminishes response efficiency
      when action must be directed toward previously ignored information.

PMID- 11949717
TI  - Divergent findings regarding negative priming in Parkinson's disease: A comment
      on Filoteo et al. (2002) and Wylie and Stout (2002).
AB  - This commentary discusses divergent findings in 2 articles published in this
      issue of Neuropsychology. The studies used negative priming (NP) to probe the
      associations between basal ganglia function and cognition in Parkinson's disease
      (PD) and tested different predictions about NP in PD. Different NP tasks were
      used, and although the subject samples appeared to have similar clinical
      features, results were quite different. This commentary, written jointly by the
      authors of the 2 studies (J. V. Filoteo, L. M. Rilling, & D. L. Strayer, 2002; S.
      A. Wylie & J. C. Stout, 2002), describes a process by which their disparate
      results may be used to facilitate the design of new studies that may determine
      how specific features of NP tasks lead to different findings in PD. The results
      are a more systematic account of how task features, such as specific response
      demands, interact with the response selection processes that are implemented by
      the basal ganglia.

PMID- 11949719
TI  - Dichotic listening and corpus callosum magnetic resonance imaging in relapsing
      remitting multiple sclerosis with emphasis on sex differences.
AB  - Twenty-five early-onset relapsing-remitting multiple sclerosis patients (12 women
      and 13 men) with mild disability were compared with 25 matched controls in a
      dichotic listening (DL) test under nonforced and forced attentional-shift
      conditions. Patients showed left ear impairment and no left ear advantage in the
      forced-left condition. Four corpus callosum (CC) regions were measured in
      patients on a midsaggital magnetic resonance imaging scan. The right ear score
      was negatively correlated whereas the left ear score was positively correlated
      with CC regions (significant only for the nonforced condition). Moreover, in men,
      the correlations with DL scores were linked mainly to the splenium and posterior
      isthmus, and in women, they were stronger for anterior isthmus and posterior
      body. An inverse correlation between months of disease evolution and CC area was
      found only in women.

PMID- 11949720
TI  - Seroepidemiology of Helicobacter pylori infection in hellenic navy recruits.
AB  - BACKGROUND AND AIMS: To investigate the prevalence of Helicobacter pylori (HP)
      infection, as well as possible risk factors affecting its acquisition among young
      Greek adults. METHODOLOGY: Sera were collected from 153 male young Hellenic Navy
      recruits (mean age 23.6 y.o.; range, 20-30 y.o.) at induction into the Hellenic
      Navy during January 1999. An enzyme-linked immunosorbent assay was used to detect
      HP-specific-IgG antibodies. All the subjects completed a structured questionnaire
      regarding demographic and socioeconomic data, as well as dietary habits, alcohol
      and tobacco use and gastrointestinal complaints. Statistical analysis was
      performed using logistic regression and the chi2 test. RESULTS: The observed
      crude seropositivity rate was 19.01%. Among the examined parameters the most
      important predictive variable for HP-IgG status was the current median family
      income (B = +0.98, SE(B) = 0.56, p = 0.08, by logistic regression), which
      however, did not attain adequate statistical significance. The rate of
      seropositivity for HP that we observed is much lower than rates reported in older
      studies in this narrow-aged group in Greece. Probably the changes that ensued in
      life-style in Greece during the last 10 years resulted in a reduction in HP
      seropositivity.

PMID- 11949722
TI  - Changes in self-reported family history of breast cancer with change in case
      control status.
AB  - In order to study recall bias in self-reported family history of breast cancer,
      we selected a sample of cases and controls from a case-control study nested in a
      cohort, and compared family history reported in a questionnaire at enrollment,
      and after the development of the disease. We assessed whether changes occurred in
      self-reported familial breast cancer due to a change in health status in women
      who developed breast cancer. The kappa of agreement for maternal history of
      breast cancer was 0.92 in cases, and 1.00 in controls; the kappa for history of
      breast cancer in sisters was 0.65 in cases, 0.88 in controls. By comparing two
      questionnaires collected before the diagnosis of the cases (index date), and one
      questionnaire administered after the index date, we were able to assess that the
      changes in answer observed among the cases were recorded in the second
      questionnaire before the index date, and therefore were independent from the
      diagnosis of cancer. The study seems to suggest that change in recall is of
      limited importance when collecting family history of first degree relatives, and
      that women recall the health history of their mother better than the health
      history of their sisters.

PMID- 11949721
TI  - Use of multiple correspondence analysis and cluster analysis to study dietary
      behaviour: food consumption questionnaire in the SU.VI.MAX. cohort.
AB  - Although the effects of individual foods or nutrients on the development of
      diseases and their risk factors have been investigated in many studies, little
      attention has been given to the effect of overall dietary patterns. The main
      objectives of this study were to identify dietary patterns and groups of subjects
      with similar food consumption habits, i.e. 'dietary profiles', using multiple
      correspondence analysis and cluster analysis. A food frequency questionnaire was
      sent to a large population-based sample (2923 women and 2,180 men), recruited
      among the 'SUpplementation en VItamines et Mineraux AntioXydants' (SU.VI.MAX.)
      cohort participants in France. The food items were dichotomised in order to focus
      the study on the highest levels of consumption. Multiple correspondence analysis
      allows the construction of principal components, which optimally summarise the
      data, and enables the construction of graphical displays. An interesting property
      of these graphical displays is that associations between food items can be
      observed on various projection planes, each category of each food item being
      located at the centre of gravity of the subjects corresponding to this category.
      An ascending hierarchical classification was unsuccessfully tried in order to
      determine clusters from these principal components. Therefore, a 'dissection' of
      the cloud of points was performed according to the orientation of the axes,
      providing a readily interpretable eight-dietary profiles typology for each sex.
      This statistical approach allows identification of particular dietary patterns
      and dietary profiles, which might be more appropriate in studies of diet-disease
      associations than the single food or nutrient approach that has dominated past
      epidemiological research.

PMID- 11949718
TI  - The apolipoprotein E gene, attention, and brain function.
AB  - The epsilon4 allele of the apolipoprotein E (ApoE) gene is associated with
      alterations in brain function and is a risk factor for Alzheimer's disease (AD).
      Changes in components of visuospatial attention with ApoE-epsilon4, aging, and AD
      are described. Healthy middle-aged adults without dementia who have the ApoE
      epsilon4 gene show deficits in spatial attention and working memory that are
      qualitatively similar to those seen in clinically diagnosed AD patients. The
      findings support an association between ApoE polymorphism and specific components
      of visuospatial attention. Molecular mechanisms that may mediate the ApoE
      attention link by modulating cholinergic neurotransmission to the posterior
      parietal cortex are discussed. Studies of attention and brain function in ApoE
      epsilon4 carriers without dementia can advance knowledge of the genetics of
      visual attention, may enhance understanding of the preclinical phase of AD, and
      may lead to better methods for early AD detection.

PMID- 11949724
TI  - Prevalence of cerebral palsy in The Netherlands (1977-1988).
AB  - Children with cerebral palsy (CP) and their families often make strong demands on
      diagnostic, therapeutic, technical and social facilities. Prevalence estimates
      are needed to improve treatment and services. As recent Dutch data are not
      available, the present study aimed to assess the population prevalence of CP in
      the Netherlands. A representative Dutch area with 1.2 million inhabitants of
      which 172,000 were born between 1977 and 1988 was studied. To ascertain the
      children with CP from these birth years, medical practices (such as
      rehabilitation centres, paediatric and child neurological departments) were
      consecutively asked to contact their (supposed) CP cases. Next, a parents'
      organisation and finally regional news media assisted in the ascertainment. In
      total, 170 'supposed' CP cases underwent an expert examination. Of these 170, 127
      children proved to be definite CP-cases, yielding a 'crude' average prevalence of
      0.74 per 1,000 inhabitants (95% CI: 0.61-0.87). Under-ascertainment was
      recognised and quantified. Accordingly, the population prevalence of CP over the
      birth year period 1977-1988 was calculated as 1.51 per 1,000 inhabitants (average
      over the 12 birth years). The calculated CP prevalence rose significantly over
      time: from 0.77 (1977-1979) to 2.44 (1986-1988). This trend is in accordance with
      other studies.

PMID- 11949725
TI  - A large outbreak of Shigella sonnei gastroenteritis associated with consumption
      of fresh pasteurised milk cheese.
AB  - A large outbreak of Shigella sonnei gastroenteritis occurred in Murcia Region
      (Southeast Spain) in the winter of 1995-1996. More than 200 people were affected.
      Epidemiological investigations implicated a regionally manufactured fresh
      pasteurised milk cheese as the vehicle of infection. A case-control study showed
      a statistically significant association between the illness and consumption of
      the suspect cheese. The dispersed sale of the cheese resulted in a regional
      dissemination of the organism and people were affected in eight townships.
      Research suggested that an infected foodhandler at the cheese factory might have
      been the source of contamination and that the processing method might have
      allowed cross-contamination to occur. This study emphasises the importance of
      increasing the control of strict hygiene during the processing of fresh cheese,
      since legislation does not forbid direct contact by hand that could result in
      contamination of cheese even when the milk pasteurisation process was correctly
      performed.

PMID- 11949726
TI  - Measures to reduce HIV infection have not been successful to reduce the
      prevalence of HCV in intravenous drug users.
AB  - The objective of the study was to determine whether measures taken to prevent
      human immunodeficiency virus (HIV) infection also lead to a reduction in the
      prevalence of hepatitis C virus (HCV) infection among intravenous drug users
      (IDU). Antibodies to HCV, HIV and hepatitis B virus (HBV) were determined in IDU
      who voluntarily attended AIDS prevention and information centres for the first
      time between 1990 and 1996. Of the 5473 IDU studied, determination of HCV was
      done in 3238 cases. The prevalence of antibodies to HCV was 85%. During the first
      period studied (1990-1992), the prevalence of antibodies to HCV was 84.5%, during
      the second (1993-1994) 84.1% and during the third (1995-1996) 87%; in the case of
      HBV the prevalence during the three periods was 74.5, 67.6 and 66.8%
      respectively, and for HIV it was 41.9, 38.8 and 36.6% respectively (RR: 0.72; 95%
      confidence interval (CI): 0.65-0.81). Among drug users addicted for less than 2
      years, the trend of the prevalence of antibodies to HCV and HBV remained
      constant, while the prevalence of HIV infection decreased (RR: 0.61; 95% CI: 0.42
      0.89). Measures to prevent transmission of HIV in drug users do not lead to a
      reduction in the prevalence of HCV infection. Further study is necessary to
      obtain a better understanding of how HCV is transmitted among drug users in order
      to apply measures which are effective in preventing HCV infection.

PMID- 11949723
TI  - Associations between body height, body composition and cholesterol levels in
      middle-aged men. the coronary risk factor study in southern Sweden (CRISS).
AB  - BACKGROUND: Short body height is associated with increased risk for coronary
      heart disease; however, mechanisms are not fully explained. In this study,
      associations between body height and serum cholesterol, non-high-density
      lipoprotein (non-HDL cholesterol) and high-density lipoprotein (HDL cholesterol)
      were investigated. METHODS: Prospective cohort study of middle-aged men from
      Helsingborg, Sweden starting 1990. Two birth-year cohorts were invited at 37, 40
      and 43 years of age; participation at baseline was 991 (68%). Serum and HDL
      cholesterol, systolic and diastolic blood pressure, weight, height, waist and hip
      circumferences were measured. Non-HDL cholesterol, body mass index (BMI) and
      waist/ hip ratio (WHR) were calculated. The participants completed a
      questionnaire covering lifestyle variables. RESULTS: There were statistically
      significant inverse correlations between body height and serum cholesterol (
      0.11) and non-HDL cholesterol (-0.12). One standard deviation, 6.7 cm, taller
      body height was associated with a lower serum cholesterol (-0.12 mmol/l) and a
      lower non-HDL cholesterol (-0.13 m mol/l; p < 0.001). These associations remained
      when adjusted for BMI and WHR. Men with serum cholesterol equal to or above 6.5
      mmol/l were significantly shorter (mean 178.71 cm) than men with serum
      cholesterol below 6.5 mmol/l (mean 179.71 cm). In addition, BMI and WHR were
      positively associated with serum and non-HDL cholesterol and inversely associated
      with HDL cholesterol. The change in cholesterol levels over the six-year follow
      up was significantly associated to the change in BMI and WHR. CONCLUSIONS: Body
      height had an independent and inverse relation to serum cholesterol and non-HDL
      cholesterol in middle-aged men, and the lipid pattern suggests that the
      underlying mechanism might be different from the traditional association between
      lipids and the metabolic syndrome. Although the direct clinical implication is
      limited, our results may help to explain the association between short height and
      risk of myocardial infarction.

PMID- 11949727
TI  - Trends in asthma mortality in Italy and Spain, 1980-1996.
AB  - Asthma is a major public health problem, with variable trends in several
      countries. We analysed mortality trends from asthma in Italy and Spain between
      1980 and 1996. Overall asthma-related mortality at all ages increased between
      1980 and 1987 in both sexes in Italy, from 16.6 in 1980-1981 to 29.0 in 1986-1987
      per million males, and from 8.0 in 1980-1981 to 13.8 in 1986-1987 per million
      females, but decreased thereafter to reach 14.6 per million in males and 8.7 in
      females in 1996. The downward trends after 1987 were consistent in middle age and
      elderly population, but asthma mortality tended to rise in children and young
      adults over the last few years. In Spain, overall age-standardized mortality
      rates from asthma declined in men from 37.8 in 1980-1981 to 10.1 in 1996, and
      from 19.5 in 1980-1981 to 13.2 per million females in 1996. In women, the fall in
      mortality rates was smaller, and overall mortality was higher than in males since
      early 1990s. Trends of asthma mortality in Italy and Spain were favourable over
      the last decade.

PMID- 11949728
TI  - Evaluation of community-wide interventions: the ecologic case-referent study
      design.
AB  - In a setting of long-standing, community-wide and generally accepted prevention
      activities like youth health care services in The Netherlands, evaluative
      research in the form of experimental studies is hardly possible. Furthermore, as
      most interventions will bear fruit only after several years and the effects are
      often described in rather vague terms, even non-experimental study designs are
      fraught with possible difficulties. Although a study design using aggregate data
      is generally considered inferior or 'incomplete', in many cases, especially in
      health services research, this approach can be the only one feasible to evaluate
      the effectiveness of preventive programmes and interventions. In this article we
      present the ecologic case-referent design as a potentially expedient and valid
      method for estimating the ecologic effect of a population-wide intervention on
      the outcome rate in those populations. In this case-referent design, many
      variables are measured at the individual level, whereas the main exposure
      variable is measured at an aggregate or ecologic level. Using recently published
      studies as an example, the advantages and drawbacks of the design are discussed
      using the randomised controlled trial design as the referent study design.

PMID- 11949729
TI  - Consanguinity and advanced maternal age as risk factors for reproductive losses
      in Alexandria, Egypt.
AB  - BACKGROUND: Consanguinity has been a long-standing social habit among Egyptians.
      Estimates of consanguinity ratios in different parts of Egypt ranged from 29 to
      50%. This study aimed at delineating the role of consanguinity and advanced
      maternal age on reproductive losses in Alexandria, Egypt. METHODS: A case-control
      study, on 730 couples with history of reproductive losses and 2,081 normal
      couples, was done during the period October, 1998 until August, 2000. RESULTS: Of
      the 730 couples with reproductive losses, consanguinity frequency was 68.8% with
      56.2% first cousins. Prenatal loss and infant deaths were highly encountered
      among consanguineous marriages (p < 0.0001). In a multivariate logistic
      regression analysis, consanguinity between couples increased the relative risk of
      repeated abortion (OR: 3.95; 95% CI: 3.04-5.14), stillbirths (OR: 10.6; 95% CI:
      6.7-17.0), neonatal death (OR: 17.2; 95% CI: 10.8-27.3), post-neonatal death (OR:
      14.5; 95% CI: 10.6-19.9) and total reproductive losses (OR: 8.3; 95% CI: 6.9
      10.1). A positive association was found between advanced maternal age and
      repeated abortion (OR: 3.19; 95% CI: 2.04-4.97) as well as total reproductive
      losses (OR: 2.37; 95% CI: 1.74-3.2). CONCLUSION: This study, the largest-reported
      case-control study on reproductive losses in Alexandria, strongly suggests that
      consanguinity may play a major role in the high rates of prenatal and infant
      mortality while advanced maternal age has a significant role in the causation of
      repeated abortion, and they must be taken into account for genetic counseling in
      Egypt. Because of the possibility of controlling, the study gives clear
      indications for prevention.

PMID- 11949730
TI  - Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with
      ischemic heart disease.
AB  - Several lines of evidence point to a possible relationship between vitamin D and
      cardiovascular disease. Animal experiments and observational studies in humans
      suggest vitamin D to be arteriotoxic and an association of high intake of vitamin
      D with increased incidence of ischemic heart disease (IHD). The major source of
      vitamin D in adults is vitamin D synthesized in the skin through exposure to the
      sun. In tropical environment there is a possibility of high level of solar
      exposure and enhanced serum levels of vitamin D in the population. We explored
      the relation between serum level of 25-hydroxyvitamin D3 and IHD in a case
      control study involving 143 patients with either angiographic evidence of
      coronary artery disease or patients with acute myocardial infarction and 70
      controls, all men in the age group of 45-65 years. Fasting blood samples were
      collected, serum separated and serum levels of 25-hydroxyvitamin D3 was measured
      by protein binding radioligand assay. Serum levels of cholesterol, triglyceride,
      calcium, magnesium and inorganic phosphate were also determined. Prevalences of
      diabetes, hypertension and smoking history were noted. Statistical comparisons of
      variables between cases and controls were done using chi2-tests. Multivariate
      logistic regression analysis was done to examine the association of IHD with
      serum levels of 25-hydroxyvitamin D3 controlling for selected variables. Serum
      levels of 25-hydroxyvitamin D3, calcium, inorganic phosphate, total cholesterol,
      low density lipoprotein and triglycerides were elevated in a higher proportion of
      patients, compared to controls. Serum levels of 25-OH-D3 above 222.5 nmol/l (89
      ng/ml) was observed in 59.4% of cases compared to 22.1% in controls (p < 0.001;
      unadjusted odds ratio (OR): 5.17; 95% confidence interval (CI): 2.62-10.21). When
      controlled for age and selected variables using the multivariate logistic
      regression, the adjusted OR relating elevated serum 25-hydroxyvitamin D3 levels
      (> or = 222.5 nmol/l, > or = 89 ng/ml) and IHD is 3.18 (95% CI: 1.31-7.73). Given
      the evidences for the arteriotoxicity of vitamin D, further investigations are
      warranted to probe whether the elevated serum levels of 25-hydroxyvitamin D3
      observed in patients with IHD in a tropical environment has any pathogenic
      significance.

PMID- 11949731
TI  - Determinants of HIV prevalence amongst female IDU in Madrid.
AB  - OBJECTIVE: To explore the multitude possible factors associated with HIV in a
      population of female injecting drug users (IDUs) in Madrid, Spain. DESIGN: A
      cross-sectional study was undertaken and because of the lack of sampling frame in
      this population, a convenience sample was recruited from drug treatment,
      methadone services and street settings. METHODS: Face to face interviews were
      conducted with 304 female IDUs during October 1995-March 1996. HIV status was
      determined from antibody testing of blood samples or from written confirmation of
      HIV test results from a physician. A hierarchical logistic regression model was
      used to identify direct and indirect relationships with HIV prevalence. RESULTS:
      HIV prevalence in the sample of female IDUs for which HIV status was known (n =
      262) was 63%. Factors independently associated with HIV prevalence in the
      regression analysis included: having a regular HIV positive sexual partner [odds
      ratio (OR): 12.2], age over 34 years (OR: 3.4), no fixed address (OR: 2.9), co
      infection with a sexually transmitted infection (STI) in the last year (OR: 2.8)
      and ever shared needles (OR: 2.6). CONCLUSIONS: The documentation of the context
      of risk behaviour in female IDU is important to predict the course of the
      epidemic and to develop prevention strategies. The sexual partners of female IDUs
      in Spain are important components in explaining the HIV epidemic in this
      population as other risk factors, including high risk drug taking behaviour. The
      findings also highlight the need to target homeless IDUs women and inmate women
      with outreach services offering preventive interventions. More effective STI
      prevention and control strategies are also warranted.

PMID- 11949732
TI  - Selecting the target and the message for a stroke public education campaign: a
      local survey conducted by neurologists.
AB  - In order to determine the baseline knowledge of stroke among population
      (terminology, signs and symptoms, risk factors (RF) and attitude) to select the
      best target and message, prior to educational campaigns, a structured interview
      using close-ended questions was conducted by neurologists among 1000 users of
      several Primary Health Centers around our Hospital, randomly sampled. In our
      population 10.1% totally ignores the disease; of the remainder, 50% has a good
      knowledge of signs and symptoms and 37% of RF. To be a woman, (OR: 1.7; 95% CI:
      1.2-2.5), the university education (OR: 6.6; 95% CI: 3.0-14.7), the age between
      45 and 65 years (OR: 2.5; 95% CI: 1.3-5.0) and to have an afflicted relative (OR:
      1.4; 95% CI: 1.001-2.0) are associated with a better stroke knowledge. If
      symptoms are transient, there is a trend to contact primary physicians (43.5%).
      Less than a quarter of our population have a good knowledge of the disease.
      Stroke is considered an emergency unlike TIA. The benefits of public education
      and the best message for each target population are discussed.

PMID- 11949733
TI  - Epidemiological survey of X-linked bulbar and spinal muscular atrophy, or Kennedy
      disease, in the province of Reggio Emilia, Italy.
AB  - Commencing with the work carried out during the epidemiological survey of
      amyotrophic lateral sclerosis in the period 1980-1992 and the pathology follow
      up, we carried out a perspective incidence, prevalence and mortality survey of X
      linked bulbar and spinal muscular atrophy (X-BSMA) in the province of Reggio
      Emilia in Northern Italy. Based on 11 patients (eight familial and three sporadic
      cases), the mean incidence per year for the period 1980 through 1997, as
      evaluated at the onset of symptoms, was 0.09 cases/100,000 for the total
      population and 0.19 cases/100,000 for the male population. On December 31, 1997,
      the prevalence rate was 1.6/100,000 for the total population and 3.3/100,000 for
      the male population. In the 18-year period of 1980-1997, the average yearly
      mortality rate was: 0.03 cases/100,000 per year for the total population and 0.06
      cases/ 100,000 for the male population. The average age at onset was 44.8 +/-
      10.1, and the average survival period was 27.3 +/- 2.3 years. The average age of
      the prevalence day was 58.9 +/- 14.9, and the average age at death was 71.3 +/-
      4.7 years. Whereas the incidence rate of X-BSMA in the province of Reggio Emilia
      is 16 times lower that of amyotrophic lateral sclerosis (ALS), the incidence rate
      of progressive bulbar palsy in the male population is only slightly higher than X
      BSMA; and the prevalence rate of ALS for males is two times the prevalence rate
      for X-BSMA, with overlapping of confidence intervals. X-BSMA is a rare disease,
      which is probably under-diagnosed, but due to the long survival period of this
      disease its frequency is not negligible. Because of the presence of sporadic
      cases or non-evident familial cases, it is appropriate to consider this
      diagnostic possibility in making a diagnosis of ALS in patients in whom lower
      motor neuron dysfunction or bulbar onset predominates.

PMID- 11949734
TI  - Psychiatric symptoms, functional impairment, and receptivity toward mental health
      treatment among obstetrical patients.
AB  - OBJECTIVE: To examine psychiatric symptomatology and associated functional
      impairment among pregnant women; and to examine the obstetrical patient's
      receptivity to discussion of and intervention regarding emotional distress.
      METHODS: Fifty-seven patients 16 weeks or less pregnant presenting for routine
      obstetrical appointments at a faculty practice at a major medical center
      participated in this study. Each completed a self-administered assessment packet
      regarding psychopathology, functional impairment and service utilization
      attitudes. Statistical analyses were performed using chi-square and Mann-Whitney
      tests. RESULTS: Seventeen subjects (29.8 percent) screened positive for at least
      one anxiety disorder. Fourteen of those subjects also screened positive for
      depression. Those with positive screens for either anxiety and/or depression had
      significantly higher levels of functional impairment. Only five (29.4 percent) of
      the 17 subjects with positive screens reported having discussed an emotional
      issue with their Ob/Gyn, although 14 (82.4 percent) said that they would be
      willing to do so. All subjects (100 percent) reported that they would see a
      mental health professional if their Ob/Gyn referred them. CONCLUSION: Routine
      screens for mental disorders in early pregnancy appear to be a useful adjunct in
      an obstetrical setting. Although most had never discussed their emotional
      concerns with their Ob/Gyn, a substantial proportion of our study sample reported
      psychiatric symptomatology and significant levels of functional impairment that
      had not been recognized by their Ob/Gyn. All of the patients in our study sample
      reported a willingness to see a mental health professional if their Ob/Gyn
      referred them. Further studies investigating the benefits of antenatal diagnosis
      and treatment of psychiatric disorders are warranted.

PMID- 11949735
TI  - T3 blood levels and treatment outcome in depression.
AB  - OBJECTIVE: We examined the correlation between the basal triiodothyronine resin
      uptake (T3-RU) levels in depressed subjects and the response to anti-depressant
      treatment. METHOD: We treated with fluoxetine 235 outpatients meeting DSM-IV
      criteria for major depression. We measured T3 resin uptake (T3-RU) levels before
      the onset of treatment. The 17-item Hamilton Rating Scale for Depression (Ham-D
      17) was administered before, during and after the eight weeks of treatment to
      assess changes in depressive symptoms. RESULTS: 16 patients (6.8 percent) had low
      T3-RU levels (range 16.5-21), and 7 patients (3.0 percent) had high T3-RU levels
      (range 36-38). No relationship was found between T3-RU levels and clinical
      improvement, defined as either total Ham-D-17 score change or Ham-D-17 score < or
      = 7 in the last 3 weeks of treatment, even after adjusting for baseline severity
      of depression. CONCLUSION: Abnormal T3-RU levels are rather uncommon in
      outpatient depression and do not correlate with the response to antidepressant
      treatment or lack thereof.

PMID- 11949737
TI  - The development and evaluation of the brief depression screen in medically ill
      disability claimants.
AB  - OBJECTIVE: There is literature demonstrating elevated prevalence of depression in
      primary care. Yet there remains a need for a brief depression screen designed and
      evaluated specifically for use among medically ill patients. Our objective was to
      develop and validate a brief, unobtrusive screen for depression among severely
      medically ill long-term disability claimants. METHODS: The study sample consisted
      of 480 long-term disability claimants, less than 55 years of age, with one of the
      following illnesses: cancer, diabetes, myocardial infarction, rheumatoid
      arthritis, stroke, or multiple sclerosis. Each subject completed a questionnaire
      that included 26 potential screening items. A subset of subjects was administered
      the SCID, which served as the gold standard for the DSM-IV depression and
      dysthymia diagnoses. RESULTS: The Brief Depression Screen, a three-item screen
      for major depressive disorder and dysthymia, was developed. About 34 percent of
      the sample met criteria for major depressive disorder or dysthymia. The Brief
      Depression Screen detected 75 percent of those subjects in this sample.
      Furthermore, nearly half of the subjects with positive screen results met
      criteria for depression or dysthymia. These results are comparable to those of
      the eight-item Burnam screen, but not as sensitive as the more widely used,
      twenty item CES-D. CONCLUSION: The Brief Depression Screen was developed and
      evaluated for use with severely ill long-term disability claimants. In practice,
      a positive screen for depression is to be followed with a comprehensive
      diagnostic assessment that could be conducted by a trained clinician. Further
      research is warranted to determine whether the identification and treatment of
      depression in disability claimants with non-psychiatric medical illnesses will
      facilitate return to work, even in the presence of comorbid medical illnesses.

PMID- 11949736
TI  - Psychological reactions among family members of patients with implantable
      defibrillators.
AB  - OBJECTIVE: To describe psychological reactions among family members of patients
      receiving an implantable cardioverter/defibrillator (ICD) during the first 9
      months after implantation. METHODS: Eighty-two family members (age 56+/-12 years,
      74 percent female, 79 percent married, 88 percent Caucasian) of ICD patients
      completed questionnaires regarding their mood (Profile of Mood State), cognitive
      illness appraisals (Meaning of Illness Questionnaire) and coping strategies
      (Jalowiec Coping Scale) prior to ICD implantation, and as well as 1 and 9 months
      postoperatively. RESULTS: Total mood disturbance score (TMD), threat appraisal,
      and emotion- and problem-focused coping were highest prior to ICD implantation,
      and decreased during the first postoperative month showing stable values
      thereafter. There was no change in challenge appraisal. Multiple regression
      analysis found that the use of psychotropic drugs (anxiolytics, sedatives; Beta =
      .25), emotion-focused coping (Beta = .37), and challenge appraisal (Beta =-.21)
      at 1 month accounted for 26 percent of variance in TMD at 9 mon ths. CONCLUSION:
      A spouse's ICD implantation is a major stressful event for family members leading
      to a diminished mood state prior ICD implantation. Reduction in emotion-focused
      coping and the use of challenge appraisal may improve mood state in family
      members of ICD patients during early follow-up.

PMID- 11949738
TI  - Symptom differences between older depressed primary care patients with and
      without history of trauma.
AB  - OBJECTIVE: The current study explored the relationship between past traumatic
      experiences and current depression in a sample of depressed older adult primary
      care patients. METHOD: Sixty-six patients were referred from primary care to a
      psychogeriatric clinic that specialized in the treatment of unipolar depressive
      disorders. All patients received an extensive psychological assessment. RESULTS:
      Twenty-one percent had a history of trauma reported in their medical charts.
      Despite no differences found on a clinician-rated measure of depression, those
      with a trauma history had more depressive symptoms on a self-report measure.
      CONCLUSIONS: Although older patients with a history of trauma may not appear more
      depressed than a non-trauma comparison group, they may be in more psychological
      distress. The clinical implications of these findings and recommendations for
      mental health professionals are discussed.

PMID- 11949739
TI  - The relationship between attendance at religious services and cardiovascular
      inflammatory markers.
AB  - OBJECTIVE: Previous studies have shown an association between attendance at
      religious services and health, particularly cardiovascular morbidity and
      mortality. Little research has focused on religious attendance and physiological
      markers of cardiovascular risk. The purpose of this study was to explore the
      relationship between religious attendance and inflammatory markers of
      cardiovascular risk. METHOD: Nationally representative sample of non
      institutionalized United States adults aged 40 and over derived from the National
      Health and Nutrition Examination Survey III 1988-1994 (n = 10,059). The main
      outcome measures were the inflammatory system markers C-reactive protein,
      fibrinogen, and white blood cell count. RESULTS: 40.8 percent of the population
      attended religious services 40 or more times in the previous year while 22.4
      percent attended services less than 40 times and 36.8 percent attended no
      religious services at all. Non-attenders of religious services were more likely
      than attenders to have elevated white blood cell counts (p = .001), highly
      elevated C-reactive protein (p = .02), and elevated fibrinogen (p = .05). After
      adjusting for demographic variables, health status, and BMI, the association
      between religious attendance and cardiovascular markers remained. Once current
      smoking was added to the model the independent effect of religious attendance
      dropped below conventional confidence limits. CONCLUSIONS: These findings suggest
      that people who have attended religious services in the previous year are less
      likely to have elevated levels of certain inflammatory markers, however, current
      smoking has significant shared variance with religious attendance.

PMID- 11949740
TI  - An organic psychosis due to a venlafaxine-propafenone interaction.
AB  - OBJECTIVE: An extraordinary case of an organic psychosis during the treatment of
      a patient with a bipolar affective disorder. METHODS: Clinical observation and
      further investigations including monitoring of serum levels (case report).
      RESULTS: A significant interaction between venlafaxine and propafenone causes
      markedly increased serum levels of venlafaxine correlating with unexpected
      psychopathological changes. CONCLUSIONS: There is a potentially dangerous
      interaction between venlafaxine and propafenone. Serum levels of venlafaxine
      should be monitored if propafenone is added.

PMID- 11949741
TI  - A case of factitious aplastic anemia.
AB  - OBJECTIVE: We report the case of factitiously induced aplastic anemia by the
      ingestion of busulfan, a bifunctional alkylating chemotherapeutic agent used in
      the treatment of chronic myelogenous leukemia. The medical consequences and
      financial costs of this illness are reported. The reader will gain an
      understanding of the relevant clues to the diagnosis of a factitious hematologic
      illness, the psychodynamic issues present in this case and the legal, ethical and
      countertransferential issues raised by the case. METHOD: A single case review
      including medical and billing records, patient and staff interviews and
      literature review. RESULTS: The covert ingestion of busulfan by this patient
      resulted in life-threatening bone marrow suppression, bilateral aseptic hip
      necrosis, transfusion-dependent thrombocytopenia and a chronic pain syndrome. Her
      treatment was complicated by noncompliance with prescribed treatments and
      polymicrobial sepsis possibly secondary to the self-injection of feces into her
      central line. To date, the total cost of care for the treatment of this patient's
      medical complications secondary to her ingestion of busulfan exceeds
      $1,100,000.00. CONCLUSIONS: This case underscores the importance of the early
      recognition by the primary care physician of the possibility of a factitious
      etiology of hematologic abnormalities such as aplastic anemia due to the
      ingestion of bone marrow ablative medications. The index of suspicion is
      increased when the patient is a young health care provider, usually female, with
      atypical pancytopenia and an unusual disease course and response to treatment.

PMID- 11949742
TI  - Methylphenidate in a patient with depression and respiratory insufficiency.
AB  - OBJECTIVE: We report a case of severe depression in an elderly and critically ill
      patient with multiple medical complications who was treated with a combination of
      methylphenidate and sertraline. The objective of this report is to outline the
      usefulness of methylphenidate as an antidepressant in a patient with respiratory
      insufficiency. METHOD: Case description. RESULTS: The patient had a positive
      clinical response with initial mental confusion due to methylphenidate. An
      initial dose of 2.5 mg/day allowed antidepressant response and improvement of
      respiratory function permitting the removal of mechanical ventilation.
      CONCLUSION: Methylphenidate may be useful for patients with severe medical
      conditions including ventilatory insufficiency.

PMID- 11949743
TI  - The perils of time-1/time-2 psychiatric research in an internal medicine clinic.

PMID- 11949744
TI  - Unexpected findings in trauma patients dying in the intensive care unit: results
      of 153 consecutive autopsies.
AB  - BACKGROUND: The true incidence of missed injuries in trauma-related deaths is
      unknown, because in only about 60% of injury-related deaths nationwide is an
      autopsy performed. Few studies have documented the frequency of missed diagnoses
      leading to deaths specifically in the trauma ICU population. We attempted to
      evaluate the incidence and nature of missed injuries and complications in trauma-
      and burn-related deaths in our ICU given an autopsy rate of close to 100%. STUDY
      DESIGN: The medical records of all trauma- and burn-related deaths in the ICU
      over a 2-year period were reviewed retrospectively. Missed diagnoses were
      classified as class 1: major diagnosis that if recognized and treated
      appropriately might have changed outcomes; class II: major diagnosis that if
      recognized and treated appropriately would not have changed outcomes; and class
      III: minor diagnosis. RESULTS: Complete antemortem records were available for 158
      patients, of which 153 (97%) underwent autopsy. Mean age was 50 years, and 72%
      were males. Mean ICU stay was 10 15 days. Four (3%) patients had class I missed
      diagnoses: bowel infarction, meningitis, retroperitoneal abscess, and bleeding
      gastric ulcer. Twenty-five (16%) patients had class II diagnoses, and 12 (8%)
      patients had class III diagnoses. Overall, 81% of 153 patients had either class
      III diagnoses or no missed injuries or complications. Pneumonia was the most
      common missed diagnosis. CONCLUSIONS: With an autopsy rate of 97%, 3% of deaths
      bad missed major diagnoses that might have affected outcomes if recognized
      antemortem. Autopsy findings can still provide valuable feedback in Improving the
      quality of care of critically ill trauma patients.

PMID- 11949746
TI  - Removal of chest tubes in children without water seal after elective thoracic
      procedures: a randomized prospective study.
AB  - BACKGROUND: Chest tubes are often placed in children after elective thoracic
      surgical procedures. Depending on surgeon preference, tubes can be pulled
      directly from suction or after a trial of water seal. Removal of the tube without
      water seal potentially allows earlier removal, decreased postoperative pain, and
      earlier discharge from the hospital. No randomized, prospective study has been
      performed to compare the two methods to determine whether omission of the water
      seal period is safe after elective thoracic surgery in children. STUDY DESIGN:
      This is a single-blinded, randomized study conducted between June 1998 and June
      2000. Children undergoing elective, noncardiac, nonesophageal thoracic operations
      were placed into water seal or a nonwater seal groups. Groups were compared for
      development of pneumothorax or pleural effusion after chest tube removal.
      RESULTS: Fifty-two children participated in the study, with 28 in group I
      (suction) and 24 in group II (water seal). Operations included both pulmonary and
      nonpulmonary thoracic operations performed both thoracoscopically and open. No
      child developed a major pleural effusion after chest tube removal. Three children
      (11%) in group I and eight (33%) in group II developed pneumothorax. No child
      required reinsertion of the chest tube and all were successfully treated with
      observation and oxygen. There was no marked difference between the groups
      regarding development of pneumothorax, but the power of the study is low.
      CONCLUSIONS: A water seal trial is not necessary for safe removal of chest tubes
      in children undergoing elective surgery. Chest tubes can be removed safely and
      earlier when pulled directly from suction for both pulmonary and nonpulmonary
      thoracic pediatric procedures.

PMID- 11949745
TI  - Topical perioperative antibiotic prophylaxis for minor clean inguinal surgery.
AB  - BACKGROUND: In minor clean procedures, such as inguinal hernia repair and
      varicocelectomy, the efficacy of systemic perioperative antibiotic prophylaxis is
      not well established. To determine the efficacy of topical antibiotic prophylaxis
      alone in preventing postoperative wound infection in a minor urologic clean
      procedure, we retrospectively reviewed the medical records of 1,654 patients who
      had undergone microsurgical varicocelectomy. STUDY DESIGN: From September 1985
      until December 2000, 1,654 men underwent 2,554 microsurgical varicocelectomies
      (900 bilateral) by a single surgeon (MG). The skin was shaved and then prepped
      with standard Betadine gel (Purdue Frederick) that was wiped away with 70%
      ethanol. No systemic antibiotics were used. The wound was irrigated with 1%
      neomycin at the moment the incision was made, and then every few minutes until
      the completion of the procedure, which averaged 45 minutes per side. No
      postoperative antibiotics were used. RESULTS: No wound infections occurred. No
      patient developed an adverse reaction to topical application of neomycin. One can
      conclude that the infection rate in this study is no higher than 0.2% with 95%
      confidence. CONCLUSIONS: Our review of a large series of consecutive clean
      urologic procedures indicates that by combining a skin preparation of Betadine
      gel and 70% ethanol with perioperative topical neomycin irrigation at the moment
      of skin incision, the risk of postoperative wound infection when performing
      microsurgical varicocelectomy can be effectively reduced to less than 0.2%.

PMID- 11949747
TI  - Surgical bypass for subclavian vein occlusion in hemodialysis patients.
AB  - BACKGROUND: The majority of patients with end-stage renal disease are dependent
      on hemodialysis. Significant stenosis or occlusion of the subclavian vein is
      known to occur in 20% to 50% of patients who have had central venous catheters
      inserted into the subclavian vein or the internal jugular vein. Surgical bypass
      of the obstructed venous segment proximal to a functioning dialysis access site
      is an established treatment to relieve symptoms and salvage the functional
      dialysis access. STUDY DESIGN: A retrospective review of all subclavian venous
      bypass procedures performed at St Louis University Hospital from May 1987 to May
      2000 was undertaken. Twelve procedures were performed during this time. The mean
      age of the patient was 55.5 years (range 17 to 72 years). There were 11 men and 1
      woman. Before surgical bypass, all patients underwent bilateral venograms to
      evaluate their central venous systems. RESULTS: An extraanatomic surgical bypass
      was performed in all patients. Patients were followed for a mean of 16 months
      (range 1 to 79 months). At 1 month, 100% of hemodialysis access sites remained
      functional. At 1 year, 80%; 2 years, 60%; and 3 years, 25% of the salvaged
      arteriovenous hemodialysis access sites provided for functional dialysis. One
      patient required thrombectomy of the bypass graft at 14 months. CONCLUSIONS:
      Surgical bypass of an occluded or stenotic subclavian vein segment is successful
      in providing both symptomatic relief and salvage of a functioning dialysis access
      in the hemodialysis patient population. Study of the central venous system is
      essential in selecting an appropriate bypass procedure in individual patients.

PMID- 11949749
TI  - Completely resected recurrent soft tissue sarcoma: primary anatomic site governs
      outcomes.
AB  - BACKGROUND: We define the natural history and influence of primary anatomic site
      for completely resected locally recurrent soft tissue sarcoma (STS) without
      distant metastasis. STUDY DESIGN: We selected 290 patients having at least one
      local recurrence (LR) after complete resection of primary STS (all sites) between
      1982 and 1999. Of these, 239 patients had complete resection of their first LR:
      161 extremity-trunk and 78 retroperitoneal-head and neck-visceral-thoracic
      sarcomas. Study end points included second local recurrence-free survival,
      distant recurrence-free survival, and disease-specific survival, estimated by the
      Kaplan-Meier method. Univariate and multivariate analyses were performed using a
      log-rank test and Cox's proportional hazards model for extremity-trunk and
      retroperitoneal (RP; n 39) tumor sites only. RESULTS: Median followup was 82
      months. Complete gross resection rates declined with each subsequent recurrence.
      Primary tumor site (extremity-trunk: relative risk ERR] 0.74, confidence interval
      [CI] 0.57 to 0.96, p = 0.03) and microscopic resection margin (negative: RR 0.80,
      CI 0.62 to 0.99, p 0.04) independently predicted subsequent local control.
      Extremity-trunk sire and high tumor grade were significant independent predictors
      of distant disease relapse after complete resection of LR. Site also had a
      notable influence on disease-specific survival: RP recurrence was associated with
      1.4 times increased risk of tumor-related mortality (p = 0.02; 5-year disease
      specific survival: extremity-trunk 70% versus RP 57%). High tumor grade was the
      most marked predictor of tumor-related mortality (RR 1.66, CI 1.28 to 2.18,
      p<0.001. Nine percent of extremity-trunk and 77% of RP STS-related deaths were
      caused by advanced LR without synchronous metastasis. CONCLUSIONS: Site governs
      local control, distant recurrence-free and disease-specific survival for
      completely resected locally recurrent sarcoma without metastasis. Distant disease
      relapse determines outcomes for recurrent extremity-trunk STS, and local
      recurrence is the determinant of tumor-related death in the RP.

PMID- 11949748
TI  - Limb-sparing resections of the shoulder girdle.
AB  - BACKGROUND: Limb-sparing surgeries around the shoulder girdle pose a surgical
      difficulty, because tumors arising in this location are frequently large at
      presentation, are juxtaposed to the neurovascular bundle, require en bloc
      resection of proportionally large amounts of bone and soft tissues, and
      necessitate complex resection and reconstruction. STUDY DESIGN: Between 1980 and
      1997, we treated 134 patients who presented with 110 primary malignant, 12
      metastatic, and 12 benign aggressive bone and soft tissue tumors of the shoulder
      girdle and subsequently underwent a limb-sparing resection. Reconstruction of the
      bone defect included 92 proximal humerus and 9 scapular prostheses. All patients
      were followed up for a minimum of 2 years. We summarize the principles of limb
      sparing resections of the shoulder girdle, with emphasis on the surgical anatomy
      of the shoulder girdle, principles of resection and reconstruction, and
      functional outcomes. RESULTS: Function was estimated to be good or excellent in
      101 patients (75.4%), moderate in 23 patients (17.1%), and poor in 10 patients
      (7.5%). Complications included 13 transient nerve palsies, 2 deep wound
      infections, and 1 prosthetic loosening. Local tumor recurrence occurred in 5 of
      103 (4.9%) patients with primary sarcomas of the shoulder girdle. CONCLUSIONS:
      Detailed preoperative evaluation and surgical planning are essential for
      performing a limb-sparing resection around the shoulder girdle. Local tumor
      control, associated with good functional outcomes, is achieved in the majority of
      patients.

PMID- 11949750
TI  - Crohn's colitis: experience with segmental resections; results in a series of 84
      patients.
AB  - BACKGROUND: Colonic Crohn's disease can be treated surgically by total colonic
      resection or by segmental colonic resection. The aim of this study was to analyze
      the outcomes of patients treated by segmental colectomy for colonic Crohn's
      disease. STUDY DESIGN: Among 413 patients undergoing operations for Crohn's
      disease, 84 had a segmental colectomy (cases of terminal ileitis with limited
      cecal involvement were not included). Postoperative complications, mortality,
      recurrence, and functional results were studied. RESULTS: Eighty-four patients
      (51 women, 33 men), with a mean age of 34 years, underwent operation (right
      segmental colectomy: 55%; left segmental colectomy: 40%; associated right and
      left colectomy: 5%). A stoma was established in 27 patients (32%). Operative
      mortality was zero. Twelve patients (14%) had postoperative complications
      (including six cases of anastomotic leakage). The mean and median followup times
      were 111 and 104 months, respectively (range: 15 to 276 months) for the 82
      patients with followup available. Thirty-six patients had to undergo reoperation,
      and the mean time to reoperation was 4.5 years. Twenty-six of these patients
      suffered colonic recurrence and were treated by total colectomy (n = 9) or new
      segmentary resection (n 17). The only factor that correlated with the risk of
      recurrence was youth. At the end of the study, 13 patients still had a stoma.
      Seventy-five percent of the patients without stoma had less than three bowel
      movements per day, and 80% were fully satisfied or satisfied, CONCLUSIONS: There
      is no evidence of a higher risk of postoperative complications, surgical
      recurrence, or the requirement of a permanent stoma in patients suffering from
      colonic Crohn's disease who are treated according to a "bowel-sparing policy"
      compared with patients treated with more extensive resections published in the
      literature. Prospective randomized studies are needed to validate this
      observation.

PMID- 11949751
TI  - Permeability and functionality of pancreaticogastrostomy after
      pancreaticoduodenectomy with dynamic magnetic resonance pancreatography after
      secretin stimulation.
AB  - BACKGROUND: The aim of this study was to evaluate pancreatogastrostomy (PG)
      permeability after duodenopancreatectomy (PD) and to determine a correlation with
      pancreatic endocrine and exocrine functions. STUDY DESIGN: This prospective study
      included 19 patients who underwent PD with PG between 1992 and 1999. There were
      12 men and 7 women, with a mean age of 58 years (range 35 to 76 years). The mean
      interval between operation and evaluation was 40.3 months (range 3 to 104
      months). Indications for pancreatectomy were benign lesions (n = 13) or
      adenocarcinoma (n = 6). Histology of the pancreatic resection margin was normal
      in all patients with malignancy, and the pancreatic remnant was macroscopically
      normal without evidence of obstructive pancreatitis. Pancreatic exocrine and
      endocrine functions were respectively evaluated by fecal-1 elastase and fasting
      blood glucose concentrations. PG permeability was determined by secretin magnetic
      resonance cholangiopancreatography (Secretin-MRCP). RESULTS: Anastomotic
      permeability was considered good in seven patients (group 1, 36.8%), moderately
      stenosed in six patients (group 2, 31.6%), significantly stenosed in four
      patients (group 3, 21.1%), and obstructed in two patients (group 4, 10.5%). Fecal
      1 elastase concentration was decreased in 18 patients, with a mean concentration
      of 80 microg/g in group 1, 98 microg/g in group 2, 67 microg/g in group 3, and 0
      microg/g in group 4. There was a statistically significant correlation between
      Secretin-MRCP group and fecal-1 elastase concentration. Results of fasting
      glucose estimation were normal for 14 of 19 patients. There was no correlation
      between pancreatic endocrine function and Secretin-MRCP group. CONCLUSIONS:
      Exocrine pancreatic insufficiency was presented in 95% of the patients despite a
      PG permeability in 68.4%. These results may be explained in part by
      neutralization of pancreatic enzymatic secretions by gastric acid.

PMID- 11949752
TI  - Microelectrical mechanical systems in surgery and medicine.

PMID- 11949753
TI  - Optimizing the use of blood cultures in the febrile postoperative patient.

PMID- 11949755
TI  - Inflammatory myofibroblastic tumor of the small intestine.

PMID- 11949754
TI  - HER2/neu in the management of invasive breast cancer.

PMID- 11949756
TI  - Palliative care by the surgeon: how to do it.

PMID- 11949757
TI  - Carotid body tumors.

PMID- 11949758
TI  - Glomus vagale: paraganglioma of the vagus nerve.

PMID- 11949759
TI  - Porcine small intestine submucosa as a treatment for enterocutaneous fistulas.

PMID- 11949760
TI  - New surgical procedure for sliding inguinal hernia repair in female infants and
      girls.

PMID- 11949761
TI  - International Consensus Conference on Breast Cancer.

PMID- 11949762
TI  - Psychooncology in breast cancer treatment.

PMID- 11949763
TI  - Intrahepatic cholangiocarcinoma.

PMID- 11949764
TI  - Perihilar cancer.

PMID- 11949765
TI  - The SMART way to fight AIDS. Strategies for Management of Anti-Retroviral
      Therapies.

PMID- 11949766
TI  - The BDI of the beholder.

PMID- 11949767
TI  - Effects of ketanserin and haloperidol on prepulse inhibition of the acoustic
      startle (eyeblink) response and the N1/P2 auditory evoked response in man.
AB  - Contraction of the orbicularis oculi muscle in response to a sudden loud sound
      (acoustic startle response) and the N1/P2 component of the auditory evoked
      potential are both attenuated when a brief low-intensity stimulus is presented 30
      500 ms before the 'startle-eliciting' stimulus (prepulse inhibition). Here, we
      report the effects of the serotonin (5-HT)2 receptor antagonist ketanserin and
      the D2 dopamine receptor blocking antipsychotic drug haloperidol on these
      responses. Fifteen males (aged 18-35 years) participated in four sessions at 7
      day intervals, in which they received ketanserin 20 mg, ketanserin 40 mg,
      haloperidol 3 mg and placebo, according to a balanced double-blind design.
      Electromyographic (EMG) responses of the orbicularis oculi muscle and N1/P2
      auditory evoked potentials were recorded in a 20-min session, 3 h after ingestion
      of haloperidol or 1 h after ingestion of ketanserin. Subjects received 40 trials
      in which 1-kHz sounds were presented: (i) 40 ms, 115 dB ('pulse alone' trials),
      and (ii) 40 ms, 85 dB, followed after 120 ms by 40 ms, 115 dB ('prepulse/pulse'
      trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived
      from the pulse-alone trials and, in each case, percentage prepulse inhibition was
      calculated. Serum prolactin was measured after each treatment, and autonomic
      (heart rate, blood pressure, salivation) and psychological (visual analogue self
      ratings of mood and alertness, critical flicker fusion frequency) measures were
      taken before and after each treatment. Ketanserin 40 mg significantly reduced the
      amplitude of the EMG response and both doses of ketanserin significantly
      suppressed prepulse inhibition of the response; haloperidol had no effect on EMG
      response amplitude or prepulse inhibition. Neither drug affected N1/P2 amplitude
      or prepulse inhibition of this response. Ketanserin, but not haloperidol, reduced
      subjective alertness and critical flicker fusion frequency. Haloperidol, but not
      ketanserin, elevated serum prolactin level. These results confirm that prepulse
      inhibition of the startle response and of the N1/P2 complex have different
      pharmacological sensitivities. The ability of ketanserin to attenuate the startle
      response may reflect its sedative action, as other drugs with sedative properties
      have also been found to attenuate the startle response in man. The ability of
      ketanserin to suppress prepulse inhibition of the startle response is consistent
      with previous evidence for the involvement of 5-HTergic mechanisms in the
      regulation of prepulse inhibition in man.

PMID- 11949768
TI  - Acute performance-impairing and subject-rated effects of triazolam and temazepam,
      alone and in combination with ethanol, in humans.
AB  - The acute behavioural effects of triazolam (0.125 and 0.25 mg), temazepam (15 and
      30 mg), and placebo, alone and in combination with ethanol (0 and 0.5 g/kg), were
      assessed in 10 volunteers. Ethanol alone did not impair performance and produced
      only a few subject-rated drug effects. Triazolam and temazepam alone produced
      some performance impairment and a few subject-rated drug effects. These effects
      tended to be dose-dependent and were comparable for the two drugs across the
      range of doses tested. The triazolam-ethanol and temazepam-ethanol combinations
      produced robust performance impairment and sedative-like subject-rated drug
      effects that were similar in magnitude. The findings of the present study suggest
      that even a moderate amount of ethanol in combination with a clinical dose of
      triazolam or temazepam can cause performance impairment that might diminish an
      individual's ability to respond adequately to unexpected demands (e.g. smoke
      alarms or middle-of-the-night child care).

PMID- 11949769
TI  - The atypical antipsychotic olanzapine enhances ingestive behaviour in the rat: a
      preliminary study.
AB  - The weight gain associated with several antipsychotic drugs, most notably the
      newer 'atypical' compounds olanzapine and clozapine, introduces problems of
      compliance and morbidity in the treatment of schizophrenia. The mechanisms
      underlying this process have been little studied due to the lack of models of the
      effects of antipsychotic drugs on weight gain and/or feeding behaviour in vivo.
      Here, we report how the effects of olanzapine (0.5 mg/kg, i.p.) on ingestive
      behaviour were investigated in the food-deprived rat using a runway to food goal
      paradigm. Compared with vehicle-treated animals, olanzapine delayed the
      reductions in food intake and in running speed that occurred after the first
      trial blocks, without effects on starting speed. These results indicate that
      olanzapine can increase feeding behaviour through a suppression of satiety,
      suggesting a mechanism for its effects on weight gain and also providing an acute
      model for further assessment of the underlying pharmacology.

PMID- 11949770
TI  - Anxiogenic and depressive-like effects, but no cognitive deficits, after repeated
      moderate tryptophan depletion in the rat.
AB  - The tryptophan (TRP) depletion method has been used as a tool to investigate the
      effects of acute lowered serotonin levels in the brain. In the present study, the
      effects of this treatment were investigated in rat models of anxiety (open field
      test, home cage emergence test), depression (forced swimming test, sucrose
      preference test) and cognition (spatial discrimination learning, sustained
      attention). It was found that the repeated TRP depletion increased anxiety
      related behaviour in the open field test and increased immobility in the forced
      swimming test. The other behavioural tests did not reveal effects of treatment.
      TRP levels were decreased in plasma (34%) and hippocampus (33%) but not in the
      cortex. Stress-induced corticosterone levels were not affected after TRP
      depletion. The present findings indicate that repeated moderate TRP depletion
      leads to anxiogenic and depressive-like behaviour in the rat and corroborates the
      notion of the involvement of serotonin in these behaviours.

PMID- 11949771
TI  - Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients
      recovered on paroxetine.
AB  - The neurobiological basis of panic disorder has not been clearly established,
      although a role for serotonin (5-HT) has been postulated. It is clear that drugs
      which increase 5-HT neurotransmission are effective in treating the condition but
      how they do so remains a point of debate. The aim of this study was to determine
      if lowering brain serotonin activity using the technique of tryptophan depletion
      provoked a short-term relapse of panic symptoms in patients with panic disorder
      who had responded to drug treatment. Fourteen patients with panic disorder who
      had responded to treatment with the selective serotonin reuptake inhibitor (SSRI)
      paroxetine received a tryptophan-free amino acid drink on one occasion and a
      control drink on the other in a double-blind crossover design. In addition, they
      received an infusion of flumazenil (used as a pharmacological challenge) and
      placebo on each day. The tryptophan depleted drink produced an 87% reduction in
      plasma tryptophan concentration. Flumazenil produced a panic attack (defined by
      changes in the panic inventory) in seven out of 14 patients when tryptophan
      depleted and one out of 14 on the control day (p < 0.02). Three patients also
      experienced temporary depressive symptoms when tryptophan depleted, with no mood
      changes being seen on the control days. We conclude that rapid lowering of brain
      serotonin function can allow the precipitation of panic symptoms in response to
      flumazenil in panic disorder patients who have responded to treatment with an
      SSRI. This implies that in panic disorder increased 5-HT availability is
      important in maintaining the response to SSRIs.

PMID- 11949772
TI  - Behavioural effects of acute phenylalanine and tyrosine depletion in healthy male
      volunteers.
AB  - Acute phenylalanine and tyrosine depletion (APTD) studies have been used to
      assess the role of the cathecholaminergic system in various aspects of human
      behaviour. In this study we conducted a randomized, double-blind, controlled and
      cross-over comparison to evaluate the effects of APTD on memory, attention and
      mood in normal subjects. Twelve healthy male volunteers were included in this
      study. The subjects ingested a nutritionally balanced mixture (B) or a similar
      mixture deficient in phenylalanine and tyrosine (PT-). Before and 5 h after
      ingestion of the drink, volunteers underwent tests on mood, memory and attention.
      Results of the memory tests showed that PT- mixture impaired word recall as
      measured in Rey's test (p = 0.016). The assessment of changes in mood showed that
      the balanced mixture improved scores of as alertness (VAMS factor I, p = 0.037)
      and the PT- mixture induces an opposite effect, increased scores of anxiety
      (Profiles of Mental State composed-anxious dimension, p = 0.022). These results
      suggest that tyrosine plasma levels and cathecholamines may be important factors
      in regulating mood and memory.

PMID- 11949773
TI  - Effects of emedastine and cetirizine, alone and with alcohol, on actual driving
      of males and females.
AB  - Emedastine is registered in its country of origin (Japan) as an antihistamine for
      the indication of seasonal allergic rhinitis. Further research on the drug's
      sedating properties was needed to secure its registration elsewhere. The present
      study was designed to compare the effects of emedastine 2 mg and 4 mg twice daily
      after single and repeated doses, on actual driving performance versus those of
      cetirizine 10 mg once daily and placebo; and to determine how repeated doses of
      each drug interact with alcohol to affect driving. Each treatment was
      administered for 5 days to 19 healthy volunteers (nine men and ten women, aged 21
      45 years) according to a four-period double-blind cross-over design. Driving
      performance was measured in a standardized test between 3 and 4 h after
      administration of the morning dose on days 1, 4 and 5. Alcohol, sufficient for
      achieving a blood alcohol concentration of 0.05 g/dl was given before driving on
      day 5 of each period. Both emedastine doses similarly and significantly impaired
      driving in every test. The effects of cetirizine were less. They were significant
      over days 1, 4 and 5 combined, although not separately. Women were more impaired
      by both drugs. Alcohol increased driving impairment similarly in every condition.
      Subjects were only able to discriminate the sedating and impairing effects of the
      first dose of emedastine 4 mg from placebo. Emedastine, in oral doses of 2 mg and
      4 mg twice daily, is sedating and impairs driving. The drug could therefore
      constitute a traffic hazard and its users should be warned accordingly.

PMID- 11949774
TI  - Effects of hydrocortisone administration on cognitive function in the elderly.
AB  - Previous studies have found adverse effects of both acute and chronic elevations
      of corticosteroids on cognitive function in humans and that cortisol levels may
      predict cognitive decline in elderly subjects. However, no previous studies have
      directly investigated the effects of hydrocortisone on cognitive functioning in
      the healthy elderly. Sixteen healthy elderly subjects took part in a placebo
      controlled, double-blind, cross-over trial. Hydrocortisone 20 mg or placebo was
      administered twice, 12 h and 1 h before cognitive testing. On each occasion, a
      battery of neuropsychological tests was performed which included tests of
      attention, working memory, declarative memory and executive function. Salivary
      cortisol levels at the time of testing were elevated approximately 10-fold
      following hydrocortisone compared with placebo. No significant effects were found
      on memory or a range of other cognitive functions. The lack of effect of this
      regime of hydrocortisone is in contrast to studies in younger subjects. The
      elderly may be less sensitive to cognitive effects of short-term increases in
      cortisol levels, possibly due to an age-related downregulation of hippocampal
      glucocorticoid receptors.

PMID- 11949775
TI  - Effects of rapid tryptophan depletion on salivary and plasma cortisol in
      Alzheimer's disease and the healthy elderly.
AB  - Serotonergic function is reduced in dementia of Alzheimer type (DAT) and
      abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are also common.
      There is considerable interaction between the two systems. Effects of lowering
      brain serotonin on salivary and plasma cortisol were assessed in patients with
      DAT and in control subjects. A double-blind, cross-over design involving
      administration of two nutritionally balanced amino acid mixtures with or without
      tryptophan was used. Salivary and plasma cortisol were measured at intervals
      before and after the drink. DAT patients had higher salivary cortisol than
      controls. Despite a reduction of approximately 70% in plasma free tryptophan
      after 4 h in both groups, there was no effect on salivary or plasma cortisol. We
      conclude that, in subjects with DAT and healthy elderly subjects, acute
      tryptophan depletion had no effect on cortisol secretion.

PMID- 11949776
TI  - Tolerance and sensitization to the hypnotic effects of alcohol induced by chronic
      voluntary alcohol intake in rats.
AB  - The effect of a chronic alcohol exposure on the development of tolerance to the
      depressive effects of alcohol were examined in male Wistar rats that voluntary
      self-administered alcohol. A free-choice drinking procedure based on the limited
      access paradigm and the addition of glucose that implies an early availability of
      the alcoholic solution was used (Alcoholism Primary Praecox procedure). Alcohol
      induced sleep time (3.5 g alcohol per kg i.p.) was measured at 90 days (after 2
      months of alcohol consumption) or at 60 + 90 days old (1 or 2 months of alcohol
      consumption). The psychomotor performance was also evaluated by means of an 80
      degrees inclined screen test. Subjects that had been tested for the hypnotic
      effects at both 60 and 90 days showed a higher intake of alcoholic solution than
      the animals only tested at 90 days. The same consumption increase was observed in
      the glucose group. No significant differences between groups were observed in the
      inclined screen test. Tolerance to the hypnotic effects of alcohol was observed
      at 90 days. On the other hand, no significant differences between alcohol and
      control groups (glucose or water) were observed in the sleep time at 60 days. In
      the alcohol-drinking rats tested for two trials (60 and 90 days), sensitization
      instead of tolerance to the second hypnotic alcohol injection was seen. Tolerance
      to the hypnotic effects of alcohol observed after chronic voluntary alcohol
      consumption may provide animal models of alcoholism based on limited access to
      sweetened alcoholic solutions with construct validity.

PMID- 11949777
TI  - Effect of intracerebroventricular injection of GABA receptor agents on morphine
      induced antinociception in the formalin test.
AB  - In the present study, the effects of gamma-aminobutyric acid (GABA) receptor
      agonists and antagonists on antinociception induced by morphine in the formalin
      test were investigated in rats. Intraperitoneal (i.p.) injection of different
      doses of morphine (1, 3, 6 and 9 mg/kg) and intracerebroventricular (i.c.v.)
      injection of different doses of muscimol (0.5, 1 and 2 microg per rat) or
      baclofen (0.25, 0.5 and 1 microg per rat) induced a dose-related antinociception
      in the both first and second phases of the formalin test. The responses induced
      by muscimol or baclofen in both phases were reduced by bicuculline or CGP35348 [p
      (3-aminopropyl)-p-diethoxymethyl-phosphinic acid], respectively. Bicuculline
      alone has produced antinociception in the second phase and CGP35348 alone has had
      antinociception in both phases of the formalin test. Morphine in combination with
      different doses of muscimol or baclofen did not elicit potentiation. The opioid
      receptor antagonist naloxone reduced the response induced by muscimol in the
      second phase and baclofen in both phases of the formalin test. It may be
      concluded that central GABA(A) and GABA(B) receptor stimulation induces
      antinociception in the formalin test. However, the antinociception induced by
      GABA receptor agonists may be mediated partly through supraspinal opioid receptor
      mechanisms and, for the GABA(B) receptor agonist, through spinal and supraspinal
      opioid receptor mechanisms.

PMID- 11949779
TI  - An ultrastructural study of connective tissue in mollusc integument: II.
      Gastropoda.
AB  - We studied the ultrastructure of the subepidermal connective tissue (SEC) in
      different zones of the integument in terrestrial, marine and freshwater
      gastropods (eight species). In all cases, the SEC was a layer of loose connective
      tissue between the basal membrane (BM) of the epidermis and the connective tissue
      of the deeper muscle layers. It was of monotonous structure and not
      differentiated into layers such as are found in mammalian dermis. The
      extracellular matrix (ECM) consisted of a network of collagen fibrils of variable
      diameter, with abundant anchoring devices and proteoglycans. In six species,
      variables quantities of haemocyanin were present within haemocoelic sinuses
      present in the SEC. The thickness and density of the BM varied from species to
      species, as well as within species in the various zones of integument. The
      ultrastructure of the lamina densa (LD) was indistinguishable from that of BM in
      bivalves and similar to that in mammals, although basotubules and double pegs
      were absent. An irregularly spaced lamina lucida was usually present and was
      often shot thorough with filaments and small protrusions of the LD that connected
      with epithelial plasma membrane or with hemidesmosomes. A lamina fibroreticularis
      was not present. LD protrusions characterize the connection between BM and the
      ECM of SEC. In the terrestrial gastropods, a spongy matrix with ultrastructure
      closely similar to LD occupied large tracts of the SEC. In the mantle region of
      Arion rufus, the integumental SEC contained large cavities filled with spherical
      concretions, probably representing rudiments of a shell. In the mantle where the
      integument contained abundant muscle fibres, the BM was thick and directly
      connected to the ECM of the SEC which consisted of compact laminae of collagen
      fibrils with abundant anchoring devices. Along the edge of the foot of Patella
      ulyssiponensis, the SEC contained a layer of paramyosinic muscle fibres adhering
      to the epidermis. No differences or gradations in integumental SEC structure
      could be related to the phylogenetic position of the species examined.

PMID- 11949778
TI  - A systematic review of the use of atypical antipsychotics in autism.
AB  - Conventional antipsychotic medication is commonly prescribed to patients with
      autistic spectrum disorder. However, a high incidence of severe adverse reactions
      highlights the need to find more favourable treatments. Atypical antipsychotics
      may combine efficacy in ameliorating some autistic symptoms with a lower
      incidence of some adverse reactions. This article reviews the use of atypical
      antipsychotics in autistic disorder, with particular focus on behaviour,
      cognition and physical well-being. Thirteen studies using risperidone, three
      using olanzapine, one using clozapine, one using amisulpride and one using
      quetiapine were identified. Few firm conclusions can be drawn due to the
      limitations of the studies; however, there is an indication that risperidone may
      be effective in reducing hyperactivity, aggression and repetitive behaviours,
      often without inducing severe adverse reactions. Olanzapine and clozapine may
      also be effective; however, there is little evidence for using amisulpride or
      quetiapine in this population. Randomized trials are required to clarify the
      effectiveness of these agents.

PMID- 11949780
TI  - Keratinization in the epidermis of amphibians and the lungfish: comparison with
      amniote keratinization.
AB  - Keratinization in the epidermis of amphibians and the lungfish has been studied
      by electron microscopy, autoradiography and immunocytochemistry to determine
      whether histidine-rich proteins, filaggrin and loricrin are present. In the
      lungfish and amphibian tadpoles, anti-keratin antibodies (AE1 and AE3) stain the
      whole epidermis but not the AE2 antibody, a marker for keratinization. In adult
      epidermis, the AE2 antibody mainly stains keratinized layers, AE1 mainly stained
      basal cells, less suprabasal cells and no pre-keratinized and keratinized layers,
      and AE3 stains all epidermal layers. This staining pattern resembles that of
      amniote epidermis. Little tritiated histidine is taken up in toad epidermis at 4
      6 h post-injection but 24 h after injection the radioactivity is most
      concentrated in the replacement layer beneath the corneus. This indicates that
      protein synthesis takes place in the epidermis but, due to the metabolic
      conversion that takes place in 24 h, it is unlikely that histidine-rich proteins
      are formed. Neither filaggrin-like nor loricrine-like immunoreactivities are
      present in amphibian and lungfish epidermis. This indicates absence of histidine
      rich matrix proteins and corneous cell envelope proteins and only mucus is
      present among keratin filaments. Filaggrine-like and loricrin-like proteins are
      characteristic of amniotes epidermis and might have originated in basic amniotes
      (cotylosaurs).

PMID- 11949781
TI  - Histological effects of androgen deprivation on the adult chimpanzee epididymis.
AB  - Primate sperm acquire functional maturity, including vigorous forward motility
      and the ability to fertilize an ovum, as they transit the unique, regional
      microenvironment of the epididymal lumen. Several proteins secreted into this
      luminal fluid are epididymal-specific and androgen-dependent, and thus contribute
      potentially to sperm maturation. For the adult male chimpanzee, we report the
      effects of GnRH antagonist-induced androgen deprivation on the histology of the
      epithelia and interstitium composing the ductuli efferentes, ductus epididymis,
      proximal ductus (vas) deferens. After 21 days of androgen deprivation, epididymal
      tissues exhibit characteristic atrophic changes, including cellular
      disorganization, degradation, and loss of structures. Androgen-deprived cytoplasm
      is differentially and characteristically disrupted, vacuolated, and reduced in
      volume, resulting in decreased epithelial height and loss of stereocilia. Most
      principal cell nuclei appear hyperchromatic, smaller in size, more irregular in
      outline, and disordered in arrangement, while others appear swollen and
      vacuolated. Apical cells of the efferent ducts and the basal cells and
      microvillar borders of the ductus epididymis seem minimally affected by androgen
      deprivation. Such histologically differential responses suggest correspondingly
      that androgen is differentially essential to the maintenance of the epididymis
      and thus to normal functioning of the component tissues. Therefore, epididymal
      epithelia directly and their secretions indirectly are differentially androgen
      dependent.

PMID- 11949782
TI  - Immunocytochemical and ultrastructural characterization of endocrine cells in the
      larval stomach of the frog Rana temporaria tadpoles: a comparison with adult
      specimens.
AB  - According to immunostaining and ultrastructural patterns, Rana temporaria tadpole
      stomach displays a well-differentiated endocrine population comprising, at least,
      six cellular types: ECL, EC [serotonin], D [somatostatin] - all three of them
      abundant -, P [bombesin] - less numerous -, CCK-8 [cholecystokinin/gastrin] and A
      [glucagon/glicentin] - both very scarce. Larval endocrine cells are mainly
      located in the surface epithelium and show open or closed morphologies. Cellular
      diversity is similar in tadpoles and frogs, with the exception of
      immunoreactivity for gastrin-17, found in adults in numerous cells. Larval cells
      display mature ultrastructural traits, although with smaller secretory granules.
      The different distribution of endocrine cells, which in adults are preferentially
      located in the glands, probably refers to different functional requirements.
      However, the rich vascular plexus present in larval mucosa may be an efficient
      transport medium of surface hormones to-gastric targets. The enhancement in
      adults of endocrine population and correlative increase in hormonal secretion
      indicates a more active functional role, probably related to the shift from
      herbivorous to carnivorous habits. In summary, the tadpole gastric endocrine
      population, although not as numerous as that of adult frogs, displays
      histological traits that indicate a relevant (immunoreactive and ultrastructural
      properties, cellular diversity) and specific (surface location, relative
      abundance of open-type cells) role of local regulatory factors in amphibian
      larval gastric function.

PMID- 11949783
TI  - Immunohistochemical localization of membrane type 1-matrix metalloproteinase (MT1
      MMP) in osteoclasts in vivo.
AB  - Membrane type 1-matrix metalloproteinase (MT1-MMP) is capable of mediating
      proteolysis of extracellular matrix. The enzyme has been demonstrated in
      osteoclasts, in vitro. However, the precise localization in vivo, and therefore
      the function of the enzyme in osteoclasts, is still unclear. In this study, we
      immunohistochemically examined the localization of MT1-MMP in rat osteoclasts to
      clarify the role of MT1-MMP in osteoclastic bone resorption and bone turnover.
      The localization of MT1-MMP was visualized by the pre-embedding method using anti
      MT1-MMP antibody and horseradish peroxidase (HRP) or gold-conjugated antibody.
      Immunoreactivity of anti-MT1-MMP was found in osteoclasts at the osteoclast-bone
      interface, but it was not uniform. Ultrastructurally, the immunoreactivity
      visualized by HRP was found in sealing zone. The plasma membrane at this site
      showed an irregular border and some invaginations. Immunoreactivity was also
      found on the surface of certain small vesicles in the cytoplasm. Enhanced silver
      granules were mainly associated with the sealing membrane. In this study, we
      demonstrated, for the first time, the localization of MT1-MMP in the sealing zone
      of osteoclast in vivo. Its distribution suggests that the enzyme modifies the
      bone surface to facilitate the migration and attachment of osteoclasts as well as
      scavenging the resorption lacunae.

PMID- 11949784
TI  - Regional adaptations in three rat tendons.
AB  - Although detailed histological and immunocytochemical studies have been published
      for the rat calcanear tendon (CT), little is known of the structure, composition
      and biomechanics of the deep (DFT) and superficial (SFT) flexor tendons. In this
      study, we examined the structural specialization of these three tendons in 90-day
      old rats by applying histochemical and biochemical assays to different tendon
      regions (proximal, intermediate and distal regions of the DFT and SFT, and
      proximal and distal regions of the CT). There were regional differences in tissue
      structure, glycosaminoglycan type and content, swelling properties and in the
      amount and distribution of elastic fibers. Dermatan sulfate occurred in all
      regions, but chondroitin sulfate predominated in the intermediate region of the
      DFT and in the distal region of the CT. These two chondroitin sulfate-bearing
      regions showed swelling in water, while all other regions lost fluid in water.
      Fibrocartilaginous sites were observed on the CT, one at the insertion to the
      bone and another distally at the innermost area of the tendon. The intermediate
      region of the DFT showed round cells disposed in lacunae, while the proximal and
      distal regions were typically fibrous. The intermediate region of the SFT showed
      a wavy array of collagen bundles but neither toluidine blue staining in the
      matrix nor round cells. Elastic fibers were present in each region of the three
      tendons, but were more prominent in the intermediate zone of the SFT. These
      results demonstrate regional variation in the three tendons. Tendon
      differentiation may occur by an increase in the number of elastic fibers and by
      variations in the arrangement of collagen fibers, without fibrocartilage
      formation.

PMID- 11949785
TI  - Ultrastructural and cytochemical features of the supramedullary neurons of the
      pufferfish Diodon holacanthus (L.) (Osteichthyes).
AB  - Exceptionally high DNA contents were found in supramedullary neuron (SN) nuclei
      of the pufferfish Diodon holacanthus by quantitative microfluorimetric assay.
      This phenomenon has been explained by endoreplication, the functional
      significance of which is still unclear. In this view, the peptidergic nature and
      large dimensions make the teleostean clustered SN an interesting model for
      investigating the relationships between endoreplication, nuclear morphology and
      biosynthetic cellular activity. In this paper, we present a cytochemical and
      ultrastructural study on the SN of D. holacanthus (Tetraodontiformes). The
      nucleolar and nucleus structures suggest an intense production of ribosomal
      components in order to satisfy high cellular demands for protein synthesis.
      Accordingly, the cytoplasmic compartment presents an extensive rough endoplasmic
      reticulum, well-developed Golgi apparatus and a remarkable vesicular traffic.
      These features suggest that SN are engaged in an intense process of protein
      biosynthesis. The SN are completely surrounded by processes of different types of
      glial cells. The glial cells may be considered part of the SN cluster.

PMID- 11949786
TI  - Evidence that increased tyrosine phosphorylation causes disassembly of adherens
      junctions but does not perturb paracellular permeability in Caco-2 cells.
AB  - In this study, we report on the apparent effect of increased tyrosine
      phosphorylation events on the assembly and integrity of adherens junctions (AJs)
      and on paracellular permeability in Caco-2 cells. Cell monolayers were incubated
      with the phosphotyrosine phosphatase inhibitor vanadate/H2O2. Addition of this
      compound to monolayer resulted in disruption of the AJs, as revealed by electron
      microscopy and by a loss of membrane association of the AJ-associated protein
      uvomorulin/E-cadherin (U/E-c). However, tight junctions (TJs) were unaltered, as
      determined by measuring the transepithelial resistance (Rt), by ruthenium red
      labeling, as seen by transmission electron microscopy, and the distribution of TJ
      strands as seen in freeze-fracture replicas and by hyperphosphorylation of triton
      insoluble occludin. Also examination of vanadate/H2O2 treated cells indicated a
      specific increase in AJ-associated phosphotyrosine residues as evaluated by
      immunofluorescence microscopy, but no modification of F-actin distribution, as
      revealed by confocal laser scanning microscopy analysis. To verify that
      modulation of AJs was indeed related to tyrosine phosphorylation, we tested a
      range of distinct protein kinase inhibitors. Of the three inhibitors tested
      (tyrphostin 25, genistein and staurosporine), tyrphostin 25 completely blocked
      the effects of vanadate/ H2O2 on assembly and integrity of AJs, redistribution of
      U/E-c and phosphotyrosine labeling. Our results indicate that, after addition of
      vanadate/H2O2 to Caco-2 monolayers, specific tyrosine phosphorylation of proteins
      cause disruption of AJs, but no modifications of the TJs' structure and
      functionality. These observations suggest that, in contrast to what happens with
      epithelial cells, TJs and AJs of Caco-2 cells are regulated by independent
      mechanisms.

PMID- 11949787
TI  - Ultrastructural effects of silicic acid on primary lung fibroblasts in tissue
      culture.
AB  - Transmission and scanning electron microscopic examination of primary lung
      fibroblasts exposed in tissue culture to polymeric silicic acid (PSA) revealed
      profound cellular changes in the cell surface membranes, resulting in rapid
      endocytosis of affected membranes and formation of multivesicular bodies.
      Exposure to monomeric silicic acid did not appear to exhibit any immediate
      adverse effects. Appearance of numerous cytoplasmic vacuoles within 1 h of PSA
      exposure was easily visible by light microscopy. Electron microscopy revealed
      that PSA exposure caused formation of an 'osmiophilic' cell surface membrane.
      Numerous osmiophilic cytoplasmic blebs on the surface and subsequent endocytotic
      vesicles appeared to collapse and aggregate into multivesicular bodies. This
      study provides ultrastructural evidence of the direct interaction between lung
      fibroblasts and polymeric silicic acid, which has a dramatic effect the surface
      membrane, its subsequent internalization and cytoplasmic processing. This
      interaction could be one of the key steps in the damaging effects of silica
      containing dust.

PMID- 11949789
TI  - Morphofunctional organization of the male reproductive system of the catfish
      Iheringichthys labrosus (Lutken, 1874) (Siluriformes:Pimelodidae).
AB  - An anatomical, histological and ultrastructural study was made of the
      reproductive system and spermatogenesis of Iheringichthys labrosus. The testis
      are digitiform and consist of a sperm atogenic cranial region, a
      spermatogenic/secretory medial (transition) region, and a strictly secretory
      caudal region. The cranial region represents 66% of the total length of the
      maturing testis and its fringes or lobes have a length of 5.59 + 0.73 mm. The
      medial and caudal regions represent each 17% of the testicular length and their
      fringes have a length of 5.37 +/- 0.69 mm and 3.12 +/- 0.38 mm, respectively.
      Histologically, the cranial region of the testis is made up of seminiferous
      tubules with spermatogenic cells contained in cysts. These cells undergo
      synchronous development, inside the cysts where spermatogenesis is completed. The
      secretory caudal region does not constitute an individualized gland.
      Ultrastructurally, its secretory cells have a vesiculous nucleus and a cytoplasm
      with abundant dilated cisternae of rough endoplasmic reticulum. The caudal region
      produces a glycoproteic secretion and exhibits variable electron density during
      maturation. During the resting period, these cells are poor in synthesis
      organelles. The spermatozoa are of the primitive type, with a round head (1.56 +/
      0.11 microm), a rudimentary middle piece, and a long flagellum with a 9 + 2
      axonemal arrangement.

PMID- 11949788
TI  - Continuous gametogenesis in the neotropical freshwater teleost, Bryconops affinis
      (Pisces:Characidae).
AB  - The gametogenesis of Bryconops affinis was studied by light, transmission and
      scanning electron microscopy. The spermatogenesis is semi-cystic and spermatids
      are released into the lumen of seminiferous tubules, where spermiogenesis is
      completed. Spermatozoa have an ovoid head, a rudimentary middle piece with a
      small number of mitochondria and long flagellum (primitive spermatozoa). The
      Sertoli and Leydig cells show secretory activity during spermatogenesis. By the
      end of this phenomenon, the Sertoli cells phagocytize the residual spermatozoa,
      while the Leydig cells show involuted characteristics. With regard to the
      oogenesis process, the oocyte development was divided into four stages based on
      the cytological characteristics of the oocyte and its surrounding layers.
      Ultrastructural analysis revealed that the zona pellucida is formed during the
      previtellogenic stage. Specializations associated to the outer layer of the zona
      pellucida may be related to the egg's adherence to the substrata.

PMID- 11949790
TI  - Structural and mechanical aspects of the skin of Bufo marinus (Anura, Amphibia).
AB  - Specific biomechanical characters and some structures possibly related to them
      were investigated in the skin of the toad Bufo marinus using tensile testing
      techniques (at constant strain till rupture) as well as morphological methods
      (histological, immunohistochemical and electronmicroscopical). Mechanical
      parameters of the native skin varied considerably according to sex, individual
      variability and/or site of specimen collection. In skin strips of males and
      females excised from different parts of the body thickness ranged from 0.45 to
      0.87 mm, strain (epsilonf) from 96.52 to 211.03, tensile strength (sigmam) from
      5.72 to 9.38 MPa, and stiffness (E-modulus) from 5.76 to 6.73. The dermis of B.
      marinus is provided with a collagenous stratum compactum of considerable
      thickness, a stratum spongiosum with loosely arranged fibres and a marked
      calcified layer (substantia amorpha). Collagen appears to be the main determinant
      of skin mechanics. However, the slope of the J-shaped static stress-strain curves
      indicates elastin to be responsible for the high values of strain. Contrary to
      van Gieson and orcein staining, immunostaining with a monoclonal antibody against
      elastin revealed very few elastic fibers between collagen bundles and in the
      vertical fiber tracts (perforating bundles), but a considerable amount in the
      tela subcutanea. This was partly confirmed at the ultrastructural level by tannic
      acid staining.

PMID- 11949791
TI  - Effects of adhesive composition on microtensile bond strength to human dentin.
AB  - PURPOSE: To evaluate the role of adhesive composition (solvent and filler
      content) on microtensile bond strength (muTBS) to human dentin. MATERIALS AND
      METHODS: 15 third molars were ground to expose superficial dentin, which was
      polished to 600-grit. The dentin was etched for 15 s with 37.5% phosphoric acid,
      rinsed, and blotted with tissue paper. The surface remained visibly moist for all
      specimens. The following adhesives were applied to the etched dentin according to
      manufacturers' directions: Single Bond (SB), experimental Single Bond (with
      filler) (ExpSB), Prime & Bond NT (NT), experimental Prime & Bond NT (without
      nanofiller) (ExpNT), and One Coat Bond (with filler) (OC). Each adhesive was
      applied to three teeth, and a cylinder of resin-based composite was built up on
      the occlusal surface. After 24-hour water storage, each tooth was vertically
      sectioned with a low-speed saw to produce a series of 0.7 mm slabs. Each slab was
      then sectioned to obtain "sticks" with a cross-sectional area ranging from 0.35
      to 0.45 mm2. muTBS were determined using an Instron universal testing machine.
      Data were analyzed using one-way ANOVA, and Duncan's test. RESULTS: For filled
      adhesives, mean bond strengths ranged from 57.9 MPa for ExpSB to 48.2 MPa for NT.
      The unfilled adhesives SB and ExpNT had mean bond strengths of 75.9 MPa and 38.7
      MPa, respectively. Unfilled SB had a significantly higher mean bond strength than
      the experimental filled version. The ethanol-based adhesive SB had a
      significantly higher mean bond strength than either the nonvolatile solvent-based
      OC or the acetone-based NT.

PMID- 11949792
TI  - Effect of dentin adhesives on the enamel-dentin/composite interfacial
      microleakage.
AB  - PURPOSE: To evaluate the microleakage at the enamel-dentin resin-based composite
      (RBC) interface of 4 dentin bonding systems (DBS). MATERIALS AND METHODS:
      Standardized kidney-shaped Class V cavities were prepared on the buccal and
      lingual surfaces at the cemento-enamel junction of 90 extracted human teeth and
      restored with a microhybrid RBC (Filtek P60) following application of either
      Excite (EXC), a single component adhesive; Prompt L Pop (PLP), a self-etching
      priming bonding adhesive; Clearfil SE Bond (SEB), a self-etching adhesive; or
      OptiBond Solo (OPS), a single component adhesive. The teeth were thermocycled,
      immersed in a dye solution and sectioned. The enamel failures and the occlusal
      and cervical dentin microleakages were measured. RESULTS: Significant differences
      were evident between the self-etching adhesives and the adhesives using
      phosphoric acid (P 0.05) for the enamel. The occlusal dentin microleakage was
      similar for the four DBS. PLP presented the worst values at the cervical dentin
      margin compared to the three other DBS. Significant differences were noted
      between PLP and EXC and OPS, which performed better.

PMID- 11949793
TI  - Color and optical properties of resin-based composites for bleached teeth after
      polymerization and accelerated aging.
AB  - PURPOSE: To determine changes in color and optical properties after
      polymerization and accelerated aging of white resin-based composites (RBCs) used
      to restore bleached teeth and compare them with those of conventional shades.
      MATERIALS AND METHODS: Four white shades and two conventional shades (A2, A3) of
      two different brands of RBCs (Vitalescence, Synergy) were measured before and
      after polymerization and after accelerated aging for 150 kJ/m2. Color was
      measured according to CIE L*a*b* color scale on a reflection spectrophotometer,
      and scattering coefficient, absorption coefficient, contrast ratio and
      translucency parameter were calculated. RESULTS: After curing, the color change (
      E*) of white RBC was not significantly higher than that of conventional shade (P=
      0.05). Color change after curing was positively influenced by the change of K
      (beta = 0.55), and negatively influenced by the changes of L*, b* and S (beta = 
      0.34, -0.95 and -0.70, respectively). After aging for 150 kJ/m2, the color
      changes of white RBCs were 2.4 and 5.8, and those of conventional shade were 1.7
      and 2.9, respectively. Higher a* and b* values had a negative influence on the
      color change for both polymerization and aging.

PMID- 11949794
TI  - Fractographical analysis of resin-dentin bonds.
AB  - PURPOSE: To characterize resin-dentin bond structures of three adhesive resin
      systems using fractographic analysis to measure the area of failure at the
      fractured surface. MATERIALS AND METHODS: Flat dentin surfaces were ground
      perpendicular to the long axis of the tooth. The prepared dentin surfaces were
      treated by one of three adhesive resin systems (Mac Bond II, One-Step, and Single
      Bond). The samples were sectioned perpendicular to the adhesive interface to
      produce a square bar-shaped specimen (adhesive area: 0.9 mm2) using a diamond
      saw. A micro-tensile test was then conducted at a crosshead speed of 1.0 mm/min.
      The mean tensile bond strengths were statistically compared using one-way ANOVA
      and Fisher's PLSD test (P< 0.05). The fractured surfaces of all specimens were
      examined using SEM and the area of failure was measured using an image analyzer
      on SEM microphotographs. RESULTS: No significant differences in tensile bond
      strength were observed between Single Bond (62.1+/-18.2 MPa) and One-Step (53.8+/
      13.1 MPa) (P > 0.05). However, the bond strength of Mac Bond II (36.5+/-13.7 MPa)
      was significantly lower than that of One-Step or Single Bond (P< 0.05). At the
      fractured surface, except for the cohesive failure of the bonding resin and resin
      based composite, different failure patterns were observed for each resin system
      as follows: the failure of the hybrid layer and demineralized dentin was observed
      in the two wet bonding systems (One-Step and Single Bond) and of the hybrid layer
      but not the demineralized dentin in the self-etching primer system (Mac Bond II).
      The results demonstrated that the integrity of the hybrid layer depends on the
      adhesive system.

PMID- 11949796
TI  - Influence of a simulated oral environment on dentin bond strength of two adhesive
      systems.
AB  - PURPOSE: To evaluate in vitro the influence of different clinical conditions
      (temperature, relative humidity) on dentin bond strength. MATERIALS AND METHODS:
      Two different bonding systems were studied, ScotchBond Multi-Purpose Plus (SBMP)
      and Clearfil SE Bond (SE Bond). In the first part of the study, the different
      environmental conditions were: ambient conditions, i.e. 20 degrees C/30% relative
      humidity (RH), 30 degrees C/50% RH, 30 degrees C/65% RH, 33 degrees C/80% RH and
      35 degrees C/95% RH. In the second part, the different interfaces (dentin/primer,
      primer/adhesive and adhesive/composite for SBMP and primer/adhesive,
      adhesive/composite for SE Bond) were also studied in order to explain the results
      obtained in the first part of the study. After the bonding procedure, a composite
      cylinder (Z100) was bonded to the surface using a Teflon mold (diameter: 3
      mm/height: 5 mm). The different specimens were tested in a shear bond mode after
      a 24-hour storage in distilled water at 37 degrees C. RESULTS: For SBMP, the
      shear bond strengths decreased when temperature/RH increased. The average values
      were very low when the 35 degrees C/95% RH conditions were simulated. A study of
      the interfaces showed that the primer/adhesive interface was the most sensitive
      to the environmental conditions simulated. For SE Bond, a decrease occurred but
      only at the highest temperature/humidity conditions. The interface study did not
      provide an explanation of the results obtained in the first part of the study.

PMID- 11949795
TI  - Enamel and dentin bond strengths of single application bonding systems.
AB  - PURPOSE: To investigate the bonding ability to enamel and dentin of new single
      application bonding systems (Reactmer and One-Up Bond) and compare these with a
      commercial compomer (Clicker/F2000), and 2-step resin-based composite bonding
      systems (Fluoro Bond/Lite-Fil II A and Single Bond/Z100). MATERIALS AND METHODS:
      Labial surfaces of extracted bovine teeth were ground on wet 600-grit SiC paper
      to expose a flattened area of enamel or dentin and then washed and dried with oil
      free compressed air. These surfaces were treated according to each adhesive
      system's instructions and the restorative materials were condensed into a Teflon
      mold (2 mm height, 4 mm internal diameter) and then irradiated. The finished
      specimens were stored in 37 degrees C distilled water for 24 hours from the start
      of light exposure to the material. Then these specimens were tested in a shear
      mode at a crosshead speed of 1.0 mm/minute. The mean and standard deviation were
      subjected to an ANOVA followed by the Duncan test (P< 0.05). RESULTS: The bond
      strengths of the single application bonding systems were 12.3 to approximately
      14.5 MPa for enamel, and 13.7 to approximately 13.8 MPa for dentin. These values
      were comparable to those of the compomer (12.6 MPa for enamel, and 13.1 MPa for
      dentin), but lower than those of the two-step resin composite bonding systems
      (16.8 to approximately 21.7 MPa for enamel and 18.1 to approximately 18.4 MPa for
      dentin).

PMID- 11949797
TI  - Tensile bond strength of composite repairs on Artglass using different surface
      treatments.
AB  - PURPOSE: To determine the tensile bond strength of composite repairs applied to
      Artglass using different surface treatments. MATERIALS AND METHODS: Blocks of
      Artglass were embedded in PVC cylinders with self-cure acrylic resin and divided
      into 18 groups according to the surface treatment. Three mechanical treatments
      and six chemical treatments were combined. Mechanical treatments were: sandpaper,
      diamond bur and microetch. Chemical treatments were: Prime & Bond 2.1 (PB) only,
      phosphoric acid+PB, hydrofluoric acid (applied for 1 or 3 minutes) +PB, Artglass
      Liquid only and silane+PB. After surface treatment, a composite truncated cone
      (Charisma, shade A3) was built. Tensile test was carried out after 24 hrs storage
      in distilled water at 37 degrees C. Failure mode was assessed using a x 10
      stereomicroscope. Artglass surfaces treated mechanically and their combination
      with phosphoric acid and hydrofluoric acid were analyzed by scanning electron
      microscopy (SEM). RESULTS: Two-way ANOVA revealed that there was no statistical
      difference in bond strength among the three mechanical treatments used, except
      for the groups where Artglass Liquid and silane were used. The use of phosphoric
      acid and Artglass Liquid did not improve the bond strength of the specimens
      compared to the groups where only PB was applied, regardless of the mechanical
      treatment. Hydrofluoric acid treatment for 1 and 3 minutes reduced the bond
      strength significantly compared to the other chemical treatments. The association
      of silane with microetching resulted in a statistically higher bond strength
      compared to all the other experimental groups. SEM analysis showed that the
      application of phosphoric acid failed to promote changes in mechanically treated
      samples. On the other hand, when hydrofluoric acid was associated to either
      diamond bur or microetching, the topography created by the mechanical treatment
      was at least partially destroyed.

PMID- 11949798
TI  - Treatment of cervical dentin hypersensitivity with resin adhesives: 4-week
      evaluation.
AB  - PURPOSE: To evaluate the effectiveness of a dentin bonding agent containing HEMA
      compared to a resin emulsion in the reduction of cervical dentin hypersensitivity
      (CDH). MATERIALS AND METHODS: The study was a randomized-within-subject, double
      blind design. Twenty patients who were suffering from CDH from at least two teeth
      (canines and/or premolars) were enrolled. The subjective perceptions of pain in
      response to tactile, air blasts and cold ethyl chloride stimuli were evaluated
      using a visual analog scale (VAS) at baseline and 10 minutes, 1 week and 4 weeks
      after the treatments. Scotchbond 1 (a dentin bonding agent similar to Single Bond
      in the USA) and MS Coat (a resin emulsion), both applied according to the
      manufacturers' directions, were selected for the study. RESULTS: Multiple
      regression ANOVA for repeated measures showed that both treatments significantly
      reduced the CDS with respect the baseline values after just 10 minutes. There
      were no significant differences between the ability of the two treatments to
      reduce CDH for each of the three evaluation stimuli or for subjective evaluation.

PMID- 11949799
TI  - Radiopacity of esthetic restorative materials compared with human tooth
      structure.
AB  - PURPOSE: To compare the radiopacity of 13 restorative materials, (a conventional
      glass-ionomer cement, three resin-modified glass-ionomer cements, six polyacid
      modified resin-based composites, and three resin-based composites) to sound tooth
      structure. MATERIALS AND METHODS: 315 specimens were made of the restorative
      materials (n = 21), of 2 mm height and 4.1 mm diameter. Radiographs were taken of
      the specimens, together with the tooth structure sample and an aluminum step
      wedge. The radiopacity values of each specimen were taken using a transmission
      densitometer. RESULTS: ANOVA and Tukey's test (95% level of confidence) revealed
      that, except for a resin-based composite, a polyacid-modified resin-based
      composite, a resin-modified glass-ionomer cement and the conventional glass
      ionomer cement, all the evaluated restorative materials were more radiopaque than
      the tooth structure.

PMID- 11949800
TI  - The biocompatibility of glass-ionomer cement materials. A status report for the
      American Journal of Dentistry.
AB  - Since their introduction in the market, some 30 yrs ago, the biocompatibility
      aspects of glass-ionomer cements (GICs) have been intensively studied. In
      general, cytotoxicity of fully set conventional preparations in previous studies
      was shown to be minimal. However, a resin-modified preparation proved to be
      cytotoxic under these conditions. This product was also observed to be mutagenic,
      but data in this area are sparse and difficult to interpret. There is also
      evidence that certain GICs exert some antibacterial properties which is claimed
      to be related to the fluoride release; however, the mechanisms for this fluoride
      release are still unclear. Pulp response studies have shown conflicting results.
      However, unfavorable initial reactions, if present, resolved with time if a
      bacterial layer under the restoration and pulp exposures were prevented. Pain
      reactions after cementation of cast restorations with GICs have been reported in
      the past but there are no such reports in the more recent literature.

PMID- 11949801
TI  - Effect of handpiece tip design on the cutting efficiency of an air abrasion
      system.
AB  - PURPOSE: The aim of this study was to evaluate the effect of nozzle angle and tip
      diameter on the cutting efficiency of an air abrasion system. MATERIALS AND
      METHODS: Thirty-six extracted human third molars were air-abraded with the
      PrepStar microabrasion machine using a handpiece with either 80 degrees or 45
      degrees nozzle angles with 0.38 or 0.48 mm tip orifice diameters. The following
      parameters were held constant: abrasive particle size (27 microm), air pressure
      (80 psi), distance (2 mm) and duration (15 seconds). The cutting efficiency was
      compared using enamel, dentin and cementum substrates. Width and depth of the
      cutting patterns were analyzed and measured using scanning electron micrographs.
      RESULTS: Statistical analysis using three-way ANOVA and Duncan's Multiple Range
      test revealed that the width of the cuts was significantly greater when the
      cavities were prepared using the 45 degrees nozzle angle. Significantly deeper
      cavities were produced with the 80 degrees nozzle angle. The tip orifice of the
      nozzle influenced the cutting efficiency in softer substrates, dentin and
      cementum. Precise removal of hard tissue is best accomplished using the 80
      degrees angle nozzle tips for all types of tooth surfaces, enamel, dentin and
      cementum.

PMID- 11949802
TI  - Persistent white lesion of the lateral tongue.

PMID- 11949803
TI  - Animal models of clinical electrophysiology of vision.

PMID- 11949804
TI  - Contrast sensitivity in pigeons: a comparison of behavioral and pattern ERG
      methods.
AB  - Contrast sensitivity (CS) is often used to assess spatial and temporal vision in
      animals. Conventional behavioral psychophysical techniques are both time and
      labor intensive, whereas measurement of CS functions by means of the pattern
      electroretinogram (PERG) is considerably more rapid and efficient. Are the two
      methods comparable, however? To answer this question, contrast-sensitivity
      functions were obtained using both the PERG and behavioral psychophysics in the
      same subjects, which were White Carneaux pigeons. The stimuli, in both methods,
      were phase-reversing, contrast-modulated sweeps of sinusoidal gratings. The PERG
      CS functions were recorded via corneal electrodes and the behavioral data were
      collected using a modified staircase method that used moderate food deprivation
      and food reward. The results indicated that the PERG-CS functions had comparable
      bandwidth and peak spatial frequency to the behavioral CS functions. The PERG-CS
      functions, however, were lower on average than the behavioral curves by about
      54%. The visual acuity of the two methods, as estimated from the high-frequency
      cutoff of the CS functions, differed by 37%. Both of these values are roughly
      consistent with the square root of 2 advantage of binocular viewing (behavioral
      method) over monocular viewing (PERG method). In addition, the peak spatial
      frequency showed a decrease of 0.125 c/deg with the PERG method and bandwidth was
      reduced by approximately 0.5 octave. These findings suggest that the PERG is an
      acceptable alternative to behavioral measurement of CS functions, especially in
      animal psychophysics, if one takes into account the underestimation of CS by the
      PERG method and the small changes in peak spatial frequency and bandwidth.

PMID- 11949805
TI  - An animal model for studying cone function in retinal detachment.
AB  - In people, retinal detachment often leads to a significant loss in cone-based
      vision. Most of the animal models commonly used for studying the consequences of
      retinal detachment have rod-dominated retinas. The purpose of this investigation
      was to evaluate the possibility that the ground squirrel, a rodent with a heavily
      cone-dominated retina, might provide a useful model for studying cone function in
      retinal detachment. Corneal ERGs were recorded from ground squirrels for large
      field temporal modulations presented on a computer-controlled color monitor.
      Modulations were chosen to selectively stimulate either of the two classes of
      cone found in the ground squirrel retina. Under these test conditions, large and
      reliable cone ERGs could be readily recorded. In animals in which the retina had
      been surgically detached, the loss of cone signal was directly related to the
      number of cones in the detachment zone relative to the total cone population and
      that relationship did not differ for short-wavelength sensitive (S) and middle
      wavelength sensitive (M) cones. Surgical reattachment produced a progressive
      recovery of cone-based signals. The ground squirrel seems likely to provide a
      useful animal model for studying the dynamics of cone function in retinal
      detachment and subsequent events.

PMID- 11949806
TI  - Extraction and modelling of oscillatory potentials.
AB  - This paper considers the recommendation that Oscillatory Potentials (OP) be
      extracted by filtering in the frequency domain. This recommendation presumes that
      filtering isolates OPs from other ERG waveforms. However, we show that the
      leading edge of the a-wave has substantial frequency overlap with the OP spectrum
      at high intensities and that it contaminates these wavelets in the frequency
      domain. We propose a method of signal conditioning that removes a-waves prior to
      filtering. When this is done, the OPs show a bimodal distribution in the
      frequency domain that is well approximated by two Gaussians having means (+/-std.
      dev.) of 91.0 +/- 14.6 Hz and 153.1 +/- 17.1 Hz. This implies that two functions
      can be used to model the OPs in the time domain. However, we show that as most of
      the power of the Fourier spectrum (74%) is contained in a single Gaussian, a
      reasonable OP model can be derived by using a single function in the time domain.
      We test such a model on humans (n=5) and pigmented (n=14) and albino (n=14)
      guinea-pigs and show that it provides excellent fits to data across a range of
      flash exposures. Furthermore, changes in OP amplitude and timing between strains
      of guinea-pigs are easily detected with this model. We show that there is no
      statistical justification for making the model more complex by including multiple
      functions. Such paramatisation of the OP envelope provides a valuable and
      intuitive description of the OP waveforms in the time domain. The model provides
      an excellent description of OPs obtained with the current paradigm, however the
      single gaussian model may be deficient under stimulus conditions which produce
      highly asymmetric OP envelopes.

PMID- 11949807
TI  - Extraction and modeling of the Oscillatory Potential: signal conditioning to
      obtain minimally corrupted Oscillatory Potentials.
AB  - A method of extracting a temporally bounded component of a composite signal has
      been developed which minimizes data corruption in signal processing. The
      composite signal is windowed in the time domain, padding signals are attached,
      and finally, the conditioned signal is filtered to extract the component of
      interest. The method has been utilized to extract the Oscillatory Potential (OP)
      from the Electroretinogram (ERG). ERGs can contain impulse like transients,
      including flash artifacts and a-b wave transition, which may not be related to
      the Oscillatory Potential. Such transients will stimulate a filter, yielding its
      natural (filter) response and thus distort the actual OP signal. To avoid this
      effect, time-domain windowing and signal conditioning is used to extract the OP
      from the ERG. The extraction and modeling approach is applied to ERGs obtained
      from patients with recent monocular central retinal vein occlusion (CRVO). Model
      parameters clearly differentiate affected from fellow eyes and show subtle
      differences between eyes with benign and complicated outcomes.

PMID- 11949809
TI  - Ganzfeld ERG in zebrafish larvae.
AB  - In developmental biology, zebrafish are widely used to study the impact of
      mutations. The fast pace of development allows for a definitive morphological
      evaluation of the phenotype usually 5 days post fertilization (dpf). At that age,
      a functional analysis is already feasible using electroretinographic (ERG)
      methods. Corneal Ganzfeld ERGs were recorded with a glass microelectrode in
      anaesthetized, dark-adapted larvae aged 5 dpf, using a platinum wire beneath a
      moist paper towel as reference. ERG protocols included flash, flicker, and ON/OFF
      stimuli, both under scotopic and photopic conditions. Repetitive, isoluminant
      stimuli were used to assess the dynamic effect of pharmacological agents on the
      ERG. Single flash, flicker, and ON/OFF responses had adequately matured at this
      point to be informative. Typical signs of the cone dominance were the small
      scotopic a-wave and the large OFF responses. The analysis of consecutive single
      traces was possible because of the lack of EKG, breathing, and blink artefacts.
      After application of APB, which selectively blocks the ON channel via the mGluR6
      receptor, the successive loss of the b-wave could be observed, which was quite
      different from the deterioration of the ERG after a circulatory arrest. The above
      techniques allowed to reliably obtain Ganzfeld ERGs in larvae aged 5 dpf. This
      underlines the important role of the zebrafish as a model for the functional
      analysis of mutations disrupting the visual system.

PMID- 11949810
TI  - Electrophysiology of the postreceptoral visual pathway in mice.
AB  - Pattern VEPs have been recorded locally from the binocular portion of the primary
      visual cortex of wild type- and different transgenic mice by means of
      microelectrodes. Local pattern VEPs have been used on the one hand to obtain
      information on basic cortical layout (topography, laminar analysis) and ocularity
      (relative contribution of the contralateral and ipsilateral eye), and on the
      other hand to evaluate several aspects of visual physiology that have a
      counterpart in visual behavior (visual acuity, contrast sensitivity, motion
      sensitivity, response latency). As compared to visual behavior, pattern VEPs
      offer the advantage that several aspects of vision can be evaluated in the same
      animals, including those with poor behavior due to motor- or cognitive deficits,
      even during the postnatal development. Pattern VEPs provide a means for
      characterizing the visual phenotype of mutant mice and for the evaluation of the
      effects induced by experimental manipulation.

PMID- 11949808
TI  - Clinical electrophysiology in veterinary ophthalmology--the past, present and
      future.
AB  - The aim of this review is to introduce the reader to the world of clinical
      veterinary electroretinography. An important indication for ERG recordings in the
      dog is the early diagnosis of progressive retinal atrophy, an inherited form of
      photoreceptor degeneration, analogous to retinitis pigmentosa in humans. In most
      of the 20 canine breeds in which the disease has been studied
      electrophysiologically, changes in the ERG appear long before the appearance of
      clinical signs. This early diagnosis is a vital tool in efforts to eradicate the
      disease through preventive breeding. Pre-operative screening of canine cataract
      patients is another common indication for electroretinography in the dog. The ERG
      is also used to diagnose inherited and nutritional photoreceptor degenerations in
      the cat, and retinal disorders in a number of other animal species. The abundance
      of animal species (and breeds) seen by the veterinary ophthalmologist lends
      additional importance to the problem of a harmonized ERG recording protocol. The
      European College of Veterinary Ophthalmologists has set up a special committee to
      formulate guidelines for such a protocol. International meetings and wetlabs are
      also being organized as part of an effort to improve the quality of
      electrophysiological diagnosis that veterinary ophthalmologists provide their
      patients.

PMID- 11949812
TI  - Background adaptation in a rat model of retinopathy of prematurity.
AB  - Low dark-adapted, scotopic retinal and visual sensitivity in retinopathy of
      prematurity (ROP) could be due to disease of the inner retina, or the recently
      described rod photoreceptor abnormalities. Receptoral disease decreases catch of
      quanta from both test flashes and steady background lights; increment threshold
      functions are shifted up and right. In diseases with normal receptors but low
      retinal sensitivity due to abnormal post receptoral processing, the increment
      threshold functions are shifted up with no horizontal translation. Herein we test
      the hypothesis that the rod photoreceptors are the site of ROP disease which
      causes low dark adapted b-wave sensitivity. The effect of steady background light
      on the ERG b-wave in a rat model of ROP is studied. ERG stimulus/response
      functions were obtained using full-field stimuli in the dark-adapted state, and
      in the presence of a steady background light. In each adaptation condition, log
      sigma, the test flash intensity that produced a half-maximum b-wave amplitude,
      was calculated. In pilot experiments, the background light selected had raised
      log sigma about a log unit in controls. In dark-adapted ROP rats log sigma was
      significantly higher, 0.35 log unit, than in controls. In the presence of the
      background light, log sigma in ROP and control rats did not differ significantly
      indicating a relative shift, up and right, of the increment sensitivity function
      for the less sensitive ROP rats. The effect of the background light is consistent
      with receptoral disease causing low dark adapted b-wave sensitivity in ROP rats.

PMID- 11949811
TI  - Flash visual evoked potentials in the hypomyelinated mutant mouse shiverer.
AB  - Myelin basic protein (MBP) is an essential component of central nervous system
      (CNS) myelin, as demonstrated by shiverer mutant mice that have deletions of most
      of the Mbp structural gene. These mutants do not produce detectable MBP protein,
      and their CNS is hypomyelinated. Although the function of the visual pathway is
      presumed to be adversely affected by hypomyelination of the optic nerve, it has
      never been studied. We compared flash visual evoked potentials (FVEPs) of
      shiverer homozygotes with those of their wild-type littermates in order to
      characterize any dysfunction. There was a statistically significant delay in the
      implicit times of a negative component peaking at 85 ms and a large positive
      component peaking at 170 ms in the FVEPs of the shiverer mice. The amplitudes of
      the two components did not differ significantly in the shiverers and wild-type
      controls. Barring a retinal pathology, which cannot be excluded by these data,
      the delayed FVEP of the shiverer can likely be attributed to effects of
      hypomyelination of the optic nerve, optic tract and visual radiations on
      conduction time in the visual pathway and subsequent further post-synaptic
      delays.

PMID- 11949813
TI  - ANAFOR: application of a restricted linear least squares procedure to NMR data
      processing.
AB  - Experimental data collection time in multidimensional nuclear magnetic resonance
      experiments can be significantly decreased if the lineshapes of all the
      components of one of the ID summations of the spectrum are known. When this
      condition is fulfilled, a simple linear least squares fit of the time-domain
      signal taking the lineshapes into account not only allows saving time in data
      collection, but also improves sensitivity and resolution. The reliability of the
      proposed procedure is carefully addressed in the particular case of Lorentzian
      lines. This strategy applied to a 3Q-REDOR experiment reduced experimental time
      by a factor of 6.

PMID- 11949814
TI  - New opportunities for high-resolution solid-state NMR spectroscopy of oxide
      materials at 21.1- and 18.8-T fields.
AB  - We present here high-resolution solid state NMR spectra of several oxide and
      silicate materials that illustrate the improvements obtainable with very high
      external fields (18.8 and 21.1 T), with probes capable of tuning to a wide
      frequency range that allow observations of nuclides from high to low magnetogyric
      ratio. We discuss 27Al MAS spectra for the zeolite scolecite (CaAl2Si3O10 x
      3H2O), 17O MAS data for analcime (NaAlSi2O6 x H2O), calcium monoaluminate
      (CaAI2O4), and titanite (CaTiSiO5), 39K spin-echo spectra for leucite (KAlSi2O6),
      microline (KAlSiO8), muscovite (KAl2(AlSi3O10)(OH2) and a potassium
      aluminosolicate glass, and preliminary 73Ge spin-echo MAS spectra for crystalline
      and glassy germanium dioxide (GeO2).

PMID- 11949815
TI  - Procedures for labeling the high-resolution axis of two-dimensional MQ-MAS NMR
      spectra of half-integer quadrupole spins.
AB  - The increasing development and application of the multiple-quantum MAS NMR for
      half-integer quadrupole spins has led to various RF pulse sequences for improving
      the excitation of multiple-quantum coherences and their conversion to single
      quantum coherences. As a result, several conventions for labeling the Fl
      dimension of a 2D MQ-MAS spectrum appear in the literature. The corresponding
      relations for extracting the isotropic chemical shift, the quadrupole coupling
      constant, and the asymmetry parameter from experimental data are not always
      provided. We analyze these various conventions systematically and propose a new
      one, similar to that introduced by J.-P. Amoureux and C. Fernandez (2000, Solid
      State NMR 10, 339-343). These various conventions are illustrated with 27Al (I =
      5/2) nuclei in aluminum acetylacetonate Al(CH3COCHCOCH3)3. Another experimental
      problem often met, the aliasing of peaks in the 2D spectrum, is analyzed and
      illustrated with 27Al (I = 5/2) in NH4Y zeolite and 23Na (I = 3/2) in sodium
      pyrophosphate Na4P2O7.

PMID- 11949816
TI  - NMR study of phase transitions in new ferroelectric Crystal--(C5H5NH)5Bi2Br11.
AB  - A T1 minimum at 216 K for Larmor frequency 90 MHz has been detected and for this
      minimum no analogous T, minimum according to the known quadratic dependence of
      the Larmor frequency 25 MHz is found. The analysis leads to the conclusion that
      this T1 minimum is a result of the relaxation of protons via quadrupole nuclei.
      The Kimmich theoretical treatment of 1H NMR experiments exhibiting the existence
      of this phenomenon in the case of relaxation of protons of piridinium cations in
      (C5H5NH)5Bi2Br11 and the estimated averaged quadrupole frequency of interacting
      quadrupole nuclei has been estimated to be around 71 MHz. Below the phase
      transition at 118 K a wide symmetric spin-lattice relaxation minimum at 25 MHz is
      detected and a model of small angle libration of the pyridinium cation has been
      applied to explain the observed T1 relaxation time minimum.

PMID- 11949817
TI  - Nuclear spin-lattice relaxation in transition metal alloys and intermetallics.
AB  - General analytical formulae describing the various contributions to the total
      spin-lattice relaxation rate in metallic materials (single crystals or powders)
      are presented. The formulae are obtained in the tight-binding approximation and
      can be easily used for any point-group symmetry. The cubic (O(h)), hexagonal
      (D(3h)), and tetragonal (D(2d)) symmetries are considered in detail.

PMID- 11949818
TI  - High-resolution heteronuclear correlation spectra between 31P and 27Al in
      microporous aluminophosphates.
AB  - A solid-state nuclear magnetic resonance (NMR) experiment, which provides high
      resolution two-dimensional heteronuclear correlation (HETCOR) spectra between
      27Al and 31P, is described. The first part of the experiment uses triple-quantum
      or quintuple-quantum magic-angle spinning (MQMAS) NMR of spin-5/2 nuclei (27Al)
      to produce an isotropic echo that is unaffected by the second-order quadrupolar
      broadening. The magnetization is then transferred to the spin-1/2 (31P) nuclei
      via cross-polarization (CP), resulting in isotropic resolution in both spectral
      dimensions. To illustrate its usefulness, this method (referred to as MQHETCOR)
      is applied to two important microporous framework aluminophosphates, hydrated VPI
      5 and AIPO4-40.

PMID- 11949819
TI  - Double-quantum filtered MAS NMR in the presence of chemical shielding
      anisotropies and direct dipolar and J couplings.
AB  - Double-quantum filtered MAS NMR spectra of an isolated homonuclear spin-1/2 pair
      are considered, at and away from rotational resonance conditions. The pulse
      sequence used is the solid-state NMR equivalent of double-quantum filtered COSY,
      known from solution-state NMR. The 119Sn spin pair in [(chex3Sn)2S] is
      characterized by a difference in isotropic chemical shielding smaller than the
      two chemical shielding anisotropies and by direct dipolar and isotropic J
      coupling constants of similar magnitudes. At rotational resonance, one
      dimensional double-quantum filtered 119Sn lineshapes yield the relative
      orientation of the two 119Sn chemical shielding tensors. Good double-quantum
      filtration efficiencies are found at and away from rotational resonance
      conditions, despite the presence of large chemical shielding anisotropies.
      Numerical simulations illustrate the interplay of the direct dipolar and J
      coupling pathways and identify the latter as the main pathway even at rotational
      resonance conditions.

PMID- 11949820
TI  - A 13C solid-state NMR investigation of the alkynyl carbon chemical shift tensors
      for 2-butyne-1,4-diol.
AB  - The alkynyl carbon chemical shift (CS) tensors for 2-butyne-1,4-diol are
      reported, based on analyses of the carbon-13 NMR spectra of stationary-powder and
      slow magic-angle spinning (MAS) samples for which the alkynyl carbon nuclei are
      enriched in 13C. NMR spectra of slow MAS samples exhibit spinning-frequency
      dependent fine structure typical of crystallographically equivalent but
      magnetically distinct nuclei. Simulated spectra of slow MAS samples of this two
      spin system are particularly sensitive to the relative orientations of the CS
      tensors. In addition, the value of 1J(13C, 13C), +175 +/- 10 Hz, is determined by
      examination of the total NMR lineshape of slow MAS samples. The CS tensors are
      almost axially symmetric, delta11 = 158.9 +/- 1.0 ppm and delta22 = 155.7 +/- 1.0
      ppm; the direction of greatest shielding is approximately along the alkynyl C-C
      bond, delta33 = -57.8 +/- 2.0 ppm. Both the magnitudes of the principal
      components of the CS tensors and their orientations are in agreement with those
      predicted from first-principles calculations at the HF and MP2 levels of theory.
      This study demonstrates the importance of examining the NMR spectra of
      homonuclear two-spin systems with and without MAS under a variety of conditions
      (e.g., two or more applied magnetic fields and slow MAS).

PMID- 11949821
TI  - MCP-1 expression in CNS-1 astrocytoma cells: implications for macrophage
      infiltration into tumors in vivo.
AB  - Gliomas are among the most resistant tumors to conventional anti-tumor therapy,
      and are typified by their highly infiltrative nature and ill-defined borders.
      Macrophages constitute a major proportion of the tumor cell mass in both primary
      human gliomas and as shown here, a CNS-1 glioma model. The objective of this
      study was to identify tumor-cell-derived chemotactic factor(s) which participate
      in macrophage recruitment into tumors in vivo. This study demonstrates the
      constitutive expression of monocyte chemoattractant protein-1 (MCP-1), a potent
      monocyte chemoattractant, by the rat astrocytoma cell line CNS-1.
      Characterization of cytokine expression by CNS-1 cells in vitro revealed the
      constitutive expression of TGF-beta but not other proinflammatory cytokines.
      However, numerous cytokines were detected in CNS-I tumors in vivo including
      Ltbeta, IL-1alpha, IL-1beta, TNF-alpha, TNF-beta, IL-10, and IFN-gamma.
      Attenuation of MCP- I release from CNS-1 cells using an anti-sense approach
      revealed no significant alterations in macrophage infiltration into tumors in
      vivo, suggesting redundancy in the signal(s) involved in macrophage recruitment.
      Depletion of peripheral macrophages using liposome-encapsulated clodronate
      revealed no significant differences in tumor growth or in the degree of
      macrophage infiltration into CNS-1 tumors in vivo. These results indicate that
      CNS-1 cells produce chemotactic factors which likely participate in macrophage
      recruitment into tumors in vivo. Whether or not macrophage recruitment confers a
      growth advantage for the tumor remains to be determined.

PMID- 11949822
TI  - Fas engagement increases expression of interleukin-6 in human glioma cells.
AB  - Although Fas (APO-1/CD95) is expressed ubiquitously and induces cell death, it is
      also known to mediate other responses such as inflammation and angiogenesis in
      vivo. Previously, we have reported that Fas ligation induces selective expression
      of chemokines (IL-8 and MCP-1) in human astroglioma cells in vitro. In this
      study, we investigated whether Fas ligation can induce expression of other
      cytokines. Expression of IL-1alpha, IL-1beta, IL-6, IL-10, IL-12, IFN-beta, IFN
      gamma, LT-beta, TGF-beta, TNF-a and TNF-beta mRNA levels in CRT-MG human
      astroglioma cells upon Fas ligation was investigated using RNase protection assay
      (RPA). We found that IL-6 mRNA is selectively induced upon Fas ligation, and IL-6
      mRNA and protein expression was further investigated using single probe RPA and
      ELISA. To investigate the in vivo expression of IL-6, human brain specimens were
      homogenized and ELISA was performed for IL-6 expression. Herein, we demonstrate
      that: (1) Among these cytokines, only IL-6 was induced upon Fas ligation in a
      dose- and time-dependent manner; (2) A selective p38 MAP kinase inhibitor,
      SB202190, and a MEK inhibitor, U0126, suppressed induction of IL-6 mRNA and
      protein expression by Fas ligation; and (3) Glioblastoma multiforme samples (n =
      11) contain significantly higher levels of IL-6 compared to those of control
      brains (n = 5), which correlate with increased levels of Fas. These results
      suggest that the Fas-FasL system may play a role in the regulation of tumor
      growth and survival by inducing the pleiotropic cytokine IL-6.

PMID- 11949824
TI  - Interleukin-6-producing cells in a human glioblastoma cell line are not affected
      by ionizing radiation.
AB  - We investigated the production of interleukin 6 (IL-6) by a radioresistant human
      glioblastoma cell line G5 after single radiation events of 3, 6 and 9 Gy. The
      total cell number and IL-6 concentration in culture supernatant were assessed 24
      96 h after irradiation. The radiation impeded or stopped G5 cell growth in a dose
      dependent manner, but unexpectedly did not affect the IL-6 concentration in cell
      culture media that increased in the same range as in non-irradiated cultures.
      Furthermore, using flow cytometry, we found that the IL-6 positive cells
      expansion was unaffected by radiation. These findings suggested that this small
      (about 1%) fraction of G5 cells, constitutively producing IL-6, is highly
      radioresistant.

PMID- 11949823
TI  - Proliferation- and apoptosis-related proteins in intracranial ependymomas: an
      immunohistochemical analysis.
AB  - As the value of grading of ependymomas is currently debated we studied the
      expression of proliferation- and apoptosis-related proteins in these tumors as
      these mechanisms both are suggested to be important in tumor growth. We
      characterized the immunohistochemical expression of p53, Mdm2, Bcl-2, and Bax in
      51 intracranial ependymomas. We also assessed the apoptosis- and proliferation
      index, measured by MIB-1, PCNA-immunohistochemistry, and analyzed the clinical
      parameters. Of all used antibodies, the correlation with survival and the
      correlation among ordered categories was assessed. None of the analyzed
      immunohistochemical variables were significantly correlated with tumor grade. On
      the other hand, PCNA, MIB-1, and p53 were significantly related to the survival
      of the patient. In multivariate analysis, p53 was the only independent predictive
      variable (p = 0.0132). CONCLUSION: The strongest predictors of survival in
      univariate analysis were the expression of PCNA, MIB-1 and p53. In multivariate
      analysis a p53 expression > 1% showed to be significantly related with a worse
      survival. The predicting value of p53 expression has to be confirmed by others
      before solid conclusions can be made. Apoptosis seems not to be an important
      mechanism in tumor growth in ependymomas. The expression of Mdm2, Bcl-2, and Bax
      were not related to survival.

PMID- 11949825
TI  - Progesterone receptor, bc1-2 and bax expression in meningiomas.
AB  - Meningiomas are generally benign central nervous system neoplasms, which
      frequently express progesterone receptor (PR) and only rarely express the
      estrogen receptor (ER). For breast cancer, a relation between steroid hormone
      receptors and proteins involved in the apoptotic process has been described. For
      meningiomas, the exact relation between PR and these proteins is not known. In
      this study, ER, PR, bcl-2 and bcl-2-associated x protein (Bax) expression levels
      were determined in meningioma cytosols. As a reference for our experimental
      conditions, we also determined these proteins in breast cancer cytosols. PR and
      ER were determined with a ligand-binding assay and scatchard-plot analysis. The
      expression levels of the anti- and pro-apoptotic proteins, bcl-2 and Bax,
      respectively, were determined by immunoblotting. In 65% of the meningioma, bcl-2
      expression was found in variable amounts. In contrast to breast cancer, a
      significant negative association between PR and bcl-2 was found (P < 0.01). Bax
      expression appeared constitutive, not related to PR, and 2.6 times higher than
      breast cancer. As both PR and bcl-2 appear positively associated with prognosis,
      the negative relationship between bcl-2 and PR found in this study might have
      some biological and clinical significance.

PMID- 11949826
TI  - BCL-2 family proteins modulate radiosensitivity in human malignant glioma cells.
AB  - Radiotherapy is the standard treatment for glioblastoma. Here, we assessed the
      radiosensitivity of 12 human malignant glioma cell lines in vitro and correlated
      these data with irradiation-induced cell cycle changes, chemosensitivity profiles
      and BCL-2 family protein expression. Irradiation at 3 Gy failed to cause major
      cell cycle perturbations. Radioresistance was associated with collateral
      sensitivity to the topoisomerase II inhibitors, teniposide and doxorubicin. High
      levels of BCL-XL and low levels of BAX were independently linked to
      radioresistance. Ectopic expression of a BAX transgene induced radiosensitization
      in the LN-18 cell line. Thus, BCL-2 family protein expression modulates
      radiosensitivity in human glioma cells and targeted alterations in BCL-2 family
      protein expression are a promising strategy to improve the therapeutic efficacy
      of radiotherapy for gliomas.

PMID- 11949827
TI  - Tamoxifen increases photodynamic therapeutic response of U87 and U25ln human
      glioma cells.
AB  - We tested the hypothesis that Tamoxifen (TMX), an inhibitor of protein kinase C
      (PKC), augments the cytotoxicity of photodynamic therapy (PDT) treatment of human
      (U87) and (U25ln) glioma cells. U87 and U25ln glioma cells were plated and
      treated with PDT using Photofrin as the sensitizer. Cells were treated with
      Photofrin at various doses and with various optical (632 nm) irradiation
      intensities 24 h later. Cells were also treated with Photofrin at a fixed dose
      alone and with various doses of Tamoxifen and subjected to laser treatment 24 h
      later. Tumor response was tested using the (3-94,5-dimethyl-2-yl)-2,5-diphenyl
      tetrazolium (MTT) method. Total toxicity of U87 cells was achieved with PDT at
      all doses of Photofrin (1, 2.5, 5, 10 microg/ml) with irradiation densities equal
      to or greater than 200 mJ/cm2. Using an irradiation intensity of 100 mJ/cm2, U87
      and U25ln cells were killed in a Photofrin dose-dependent manner. Significant
      cytotoxicity was detected with Photofrin doses of 5 microg/ml (p < 0.05) and 10
      microg/ml (p < 0.001). Tamoxifen at a dose of 500 microg/ml and higher,
      significantly increased the toxicity of the PDT response with 5 microg/ml
      Photofrin and 100 mJ/cm2 (p < 0.05). In summary, our data demonstrate that
      Tamoxifen significantly enhances the Photofrin PDT activity of U87 and U25ln
      human glioma cells.

PMID- 11949828
TI  - Nerve growth factor plays a divergent role in mediating growth of rat C6 glioma
      cells via binding to the p75 neurotrophin receptor.
AB  - Dysregulation of proliferation, differentiation and cell death play a major role
      in glial tumors, and there is evidence for regulatory mechanisms involving nerve
      growth factor (NGF) and its receptors in various CNS-derived tumor cell lines.
      The aim of our study was to observe the effect of exogenous recombinant NGF on C6
      rat glioma growth, to characterize the role of endogenous NGF and the p75
      neurotrophin receptor (p75) and to rule out whether p75 is necessary to mediate
      the effect of exogenous NGF. Recombinant exogenous NGF (1-100 ng/ml) was applied
      under different serum conditions (0%, 1%, 5%) and knockdown of endogenous NGF and
      p75 was achieved by lipid-mediated antisense oligonucleotide treatment. In
      presence of serum, NGF had a positive whereas in absence of serum NGF produced a
      negative effect on C6 cell number. A knockdown of NGF or p75 increased cell
      numbers and enhanced BrdU incorporation. In p75-knocked down cells NGF did not
      enhance C6 glioma growth in presence of serum. We conclude that (1) exogenous
      recombinant NGF enhances C6 glioma growth under serum conditions but decreases
      cell number in absence of serum, that (2) the effect of exogenous NGF is mediated
      by p75 alone or by heterodimers containing p75 and that (3) either basal levels
      of endogenous NGF or basal levels of p75 receptor moderate C6 glioma growth and
      represent an autoregulatory potential of C6 glioma cells.

PMID- 11949829
TI  - The utility of external beam radiation and intracystic 32P radiation in the
      treatment of craniopharyngiomas.
AB  - BACKGROUND: The management of craniopharyngiomas has historically been
      controversial in terms of the extent of initial surgical resection and the use of
      additional treatments. Various options include radical excision versus a more
      conservative surgical approach followed by external beam radiation; most
      recently, intracystic 32P radiation has been used in selected patients. METHODS:
      We reviewed our experience with 25 patients with craniopharyngiomas treated
      between 1984 and 1999 to assess the effectiveness of external beam radiation and
      intracystic 32P radiation therapy in preventing progression and recurrence of
      local disease. RESULTS: All patients underwent surgery as a component of initial
      therapy for their histologically-proven craniopharyngiomas. Fifteen patients
      additionally received external beam radiation. Forty-five percent of patients who
      underwent incomplete resections followed by external beam radiation required
      additional therapy. In contrast, 80% of patients who had incomplete resections
      without post-operative external beam radiation required further treatment. Seven
      patients had intracystic 32P colloid injections. Neither of the two patients
      receiving 32P intracystic radiation as part of their initial therapy needed
      further treatment. Only one of the five patients receiving 32P intracavitary
      radiation for disease progression following initial therapy required further
      intervention. Of the remaining four patients, three enjoyed responses to
      treatment and one had stable disease. CONCLUSIONS: Our observations support the
      use of external beam radiation for prevention of tumor progression in adults
      unable to receive a complete surgical resection. Our results additionally suggest
      that intracystic 32P radiation results in control of cystic components of
      craniopharyngiomas in the majority of cases.

PMID- 11949830
TI  - Intra-arterial carboplatin and intravenous etoposide for the treatment of
      recurrent and progressive non-GBM gliomas.
AB  - Recurrent and progressive non-GBM gliomas are a diverse group of brain tumors
      that often respond poorly to adjuvant chemotherapy treatment. Regional intra
      arterial (IA) administration of chemotherapy may result in increased tumor uptake
      of drug, with improvement in response rates and time to progression (TTP). Twenty
      five patients with recurrent or progressive non-GBM gliomas were treated with IA
      carboplatin (200 mg/m2/d) and intravenous (IV) etoposide (100 mg/m2/d) for 2 days
      every 4 weeks. Patients ranged in age from 22 to 68 years (mean 37.8). All but
      one patient had received standard irradiation, and eight patients had attempted
      prior chemotherapy. Five of 25 patients had objective responses (20%), while
      another 15 patients had stable disease (60%), receiving a total of 318 IA
      treatment procedures. There was one complete response (4.0%), three partial
      responses (12.0%), one minor response (4.0%), 15 stable diseases (60.0%), and
      five progressive diseases (20.0%). The median TTP was 24.2 weeks overall and 32
      weeks in responders. Overall median survival was 34.2 weeks. Therapy was well
      tolerated, with mainly hematologic toxicity. Two patients had embolic
      complications. Although these are preliminary results, IA carboplatin and IV
      etoposide have modest activity against recurrent and progressive non-GBM gliomas
      and warrants further study.

PMID- 11949832
TI  - Contemporary trends in in vivo and in vitro testing of chemical carcinogens.
AB  - In the sixties of the last century it was realized that many human cancers are
      caused by environmental carcinogens and that the best way how to reduce cancer is
      first to identify in environment chemical carcinogens and second to prevent
      people from being exposed to such carcinogens. Epidemiological studies are
      probably the only way to confirm human carcinogenesis, however, this approach is
      so retrospective that carcinogens can be identified only after many victims have
      appeared. Carcinogenicity testing in long-term, medium-term, and short-term
      studies is therefore the only way for the prospective identification of possible
      human carcinogens. End-points of interest in a carcinogenicity study are
      primarily preneoplastic and neoplastic changes, but also include degree of
      malignancy, time to tumor appearance, multiplicity of (pre)neoplasia, and
      occurence of metastases. Long-term bioassays are designed and conducted to detect
      all of these end-points. Medium-term bioassays are mainly based on the detection
      of putative preneoplastic lesions and short-term tests can provide very important
      information concerning genotoxic effects of studied compounds.

PMID- 11949831
TI  - Postoperative radiotherapy for intracranial ependymoma: analysis of prognostic
      factors and patterns of failure.
AB  - The long-term results of external beam radiotherapy following surgical resection
      in patients with intracranial ependymomas were evaluated to identify the
      prognostic factors and the pattern of recurrence. Between June 1961 and January
      1999, 48 patients with intracranial ependymoma were treated with external beam
      irradiation with >40 Gy following surgery. Total doses of 40.5-63.4Gy were
      delivered to the tumor site in 22-46 fractions over 33-101 days. Six patients
      with spinal deposit or positive cerebrospinal fluid cytology received whole
      spinal axis irradiation, and 4 patients received prophylactic spinal irradiation.
      The median follow-up of surviving patients was 110 months. The 10-year overall
      and relapse-free survival rates were 47% and 42%, respectively. In multivariate
      analysis, female gender, lower tumor grade and total resection were found to be
      associated with better relapse-free survival. Twenty of 26 recurrences developed
      at the primary tumor site (inside the irradiation field), two at the unirradiated
      cerebellum and spinal cord, and four at the spinal cord without intracranial
      failure. Only one of 34 patients with supratentorial tumors developed isolated
      spinal metastasis, whereas 3 of 14 patients with infratentorial tumors did so.
      Regarding the late neurotoxicity of radiotherapy, one of the 15 long-term (>4
      years) survivors whose psychosocial status could be evaluated showed marked
      cognitive impairment. It was suggested that the use of new treatment strategies
      to improve local control would be warranted, and that prophylactic whole spinal
      axis irradiation appeared to be of more benefit in patients with infratentorial
      tumors than in those with supratentorial tumors.

PMID- 11949833
TI  - Flavonoids as chemoprotective agents in civilization diseases.
AB  - Flavonoids, a class of polyphenolic compounds widely distributed in the plant
      kingdom, are capable of protecting against several chronic and degenerative
      diseases, among them cancer, cardiovascular diseases, stroke, cataracts and brain
      and immune dysfunctional states. These substances are common dietary components.
      They exhibit many biological properties through various mechanism of activity.
      Early studies of flavonoids investigated their significant antioxidant,
      antitumor, anti-inflammatory, antiallergenic and hepatoprotective effect.
      Additionally, their ability to modulate the activity of various enzymes affects
      normal as well as malignant systems. This review summarizes data on the
      beneficial effects of flavonoids in humans.

PMID- 11949834
TI  - Radiation-induced meningiomas.
AB  - High dose radiation-induced meningiomas are a rare, severe and late complication
      of craniospinal radiotherapy for brain tumors. Radiation-induced meningiomas are,
      according to the literature, several times more frequent than radiogenic gliomas
      and sarcomas. It is suggested that every new case of radiogenic meningioma has to
      be reported to elucidate this particular pathologic entity with its many grey
      areas. In addition to high dose radiation-induced meningiomas, intracranial
      meningiomas were observed in patients who underwent low-dose radiation for tinea
      capitis in childhood, applied en mass to immigrants coming to Israel from the
      North Africa and the Middle East during the 1950. Authors summarize the data on
      radiogenic meningiomas from the literature and, as the previous radiotherapy may
      confer a low, but life-long risk for meningioma occurrence, they suggest that
      surveillance MRI after high dose cerebrospinal radiotherapy should be extended to
      several (3-5) decades after radiotherapy.

PMID- 11949835
TI  - Germline mutation of the RET proto-oncogene in members of Slovak families with
      multiple endocrine neoplasia 2.
AB  - Detection of mutations in RET proto-oncogene in Slovak families from different
      localities and of different ethnic origin with MEN 2 syndrome is reported.
      Despite the fact that the same mutation of RET oncogene was found in different
      family members, the latency period of tumor appearance and their pathogenicity
      differed substantially. In addition, also different phenotypes of the disease
      were expressed in various family members having the same RET gene mutation. The
      data indicate that the mechanism of MEN2 syndrome is not only due to the RET gene
      mutation, and strongly support the conclusion that additional genetic events are
      involved in the disease formation.

PMID- 11949836
TI  - Mutation screening of the BRCA1 gene in Slovak patients.
AB  - Breast cancer is the most commonly observed malignancy in women of the western
      world. The family history is the strongest risk factor for the disease. Two major
      genes, BRCA1 and BRCA2 that are involved in the familial breast and ovarian
      cancer have been described. Germ-line mutations of the BRCA1 gene have been
      linked to 85% of all hereditary breast and ovarian cancers. We performed a
      mutation screening ofthe entire codingregion of the BRCA1 gene in 29 Slovak
      families suspected of having inherited predisposition to breast cancer. For the
      analysis we used a combination of a single strand conformation polymorphism
      (SSCP), denaturing high-performance liquid chromatography (DHPLC) and sequencing.
      Genetic alterations were consistently indicated by SSCP and DHPLC and
      consequently confirmed by DNA sequencing as previously described pathogenic
      mutations. The patients with inherited BRCA1 mutations will undergo genetic
      counseling and cancer prevention health care program.

PMID- 11949837
TI  - Effect of retinoic acid on the actin cytoskeleton in HL-60 cells.
AB  - The cytoskeleton, in addition to its structural and kinetic functions, is also
      involved in modulating signal transfer in cell proliferation, differentiation and
      death. In some myeloid leukemic cell lines, the process of cell differentiation
      accompanied by apoptosis, can be induced by all-trans retinoic acid (ATRA). In
      this report, we describe the morphological changes in actin cytoskeleton, taking
      place during apoptosis in cells of the human leukemic HL-60 cell line. By using
      fluorescent microscopy, the morphology of microfilaments and the proportion of
      apoptotic cells in the cell populations untreated or treated with 10(-6) M ATRA
      were detected. Interphase HL-60 cells showed aggregations of short, thick
      microfilament bundles in the region between the plasma membrane and the nucleus.
      In comparison with both interphase and mitotic cells, the cells with apoptotic
      nuclear fragmentation showed a different organisation of the actin cytoskeleton.
      The following types of F-actin structures were observed: (i) Cells with a high
      number of large dots/patches of F-actin under the plasma membrane. These dots
      might be localised only in the part of the cell or occurred under the whole
      plasma membrane. This arrangement was often associated with a diffuse signal for
      F-actin. (ii) Cells with 3D-network of F-actin fibres through the cytoplasm
      between remnants of the cell nucleus. This 3D-structure probably played an
      important active role in the process of apoptotic bodies formation. (iii) Cells
      without any detectable signal for F-actin or cells with only a very low F-actin
      signal. Both of these showed typical apoptotic collapse of chromatin. It is
      concluded that the actin cytoskeleton is a dynamic structure actively involved in
      the executive phase of the process of apoptosis. It is suggested that the
      rearrangement of the microfilament network and its subsequent degradation are
      necessary for the main morphological changes of apoptotic cells, i.e., plasma
      membrane blebbing and apoptotic bodies formation.

PMID- 11949838
TI  - Plasminogen activator inhibitor type 2: potential prognostic factor for
      endometrial carcinomas.
AB  - The clinical determination of proteases which are involved in carcinogenesis,
      invasion and metastasis may contribute to the detection of the early stage of
      disease, and to the prognostic assessment of patients with the cancer. The aim of
      the present study was to determine the level of urokinase plasminogen activator
      (uPA), plasminogen activator inhibitor type 1 (PAI-1) and plasminogen activator
      inhibitor type 2 (PAI-2) in normal and malignant tissues of corpus uteri and to
      evaluate the possible correlation with clinical and histopathological prognostic
      factors. UPA, PA-I and PAI-2 were determined by the ELISA assay in tissue cytosol
      of matched pair samples from 27 patients with endometrial carcinoma. Results show
      that significantly higher levels of these proteins were found in malignant than
      in normal tissue samples (uPA: 1.266 versus 0.633 ng/mg protein, PAI-1:4.468
      versus 1.958 ng/mg protein, and PAI-2:3.428 versus 0.483 ng/ml protein). The
      levels of uPA and PAI-1 did not correlate with clinical staging or
      pathohistological grading. However, in tumor tissues with clinical stages II and
      III, myometrial invasion > 50%, and lymphovascular invasion, increased levels of
      PAI-2 were determined. Our results indicate that components of the plasminogen
      activation cascade are up-regulated in endometrial cancer and suggest the role of
      PAI-2 in determining invasive potential of endometrial carcinomas.

PMID- 11949839
TI  - Identification of a pepsin-sensitive type III-like collagen in breast cancer MCF
      7 cells.
AB  - Electrophoretic analysis of [3H]proline-labeled culture medium proteins of MCF-7
      cells revealed the presence of disulfide-bonded, bacterial collagenase-sensitive
      component which comigrated with pro(alpha)1 chains of type III and type I
      collagens. However, it was pepsin- and trypsin-sensitive. Within 1 min of pepsin
      digestion, a component with a size of alpha1 chain of type I or III collagen was
      produced which degraded after 5 min of digestion. Similarly, the pepsin-sensitive
      band was completely degraded by trypsin at 30 degrees C within 5 min. We examined
      CNBr peptides of the collagenous band and demonstrated that it was alpha1 chain
      of type III collagen. When MCF-7 cells were cultured in the presence of 2 nM
      estradiol, a marked increase in the level of collagen secreted into medium was
      found. The identified proteinase-sensitive type III-like collagen as major
      protein of extracellular matrix, would be expected to be more susceptible to
      degradation which might contribute to tumor progression.

PMID- 11949840
TI  - Significance of P-glycoprotein expression in childhood malignant tumors.
AB  - Resistance to chemotherapy significantly affects the treatment results in various
      cancers. Multidrug resistance caused by P-glycoprotein expression is now widely
      studied in human malignancies. We present the results of P-glycoprotein
      expression examination in 91 tumor tissue samples obtained from children treated
      for different malignant tumors in the Dept. of Pediatric Oncology, Prague. The
      correlation between the level of P-glycoprotein expression and tumor histology,
      clinical outcome, use of therapy, relapse rate and metastatic disease was made. P
      glycoprotein expression was found significantly more frequent in soft tissue
      sarcomas, neuroblastomas, and hepatoblastomas, and generally in disseminated
      disease. On the contrary, a high expression of P-glycoprotein was not found in
      malignant brain tumors and nephroblastomas. The data strongly support the
      possibility that the percentage of P-glycoprotein expressing cells in selected
      tumors (soft tissue sarcomas, neuroblastomas), may have a clinical importance.

PMID- 11949841
TI  - Establishment, morphological, growth and cytoskeletal properties of 135-BCA
      carcinoma cell line derived from lung brain metastasis.
AB  - Many cell lines have been established from lung cancer but carcinoma cell lines
      derived from brain metastases occur rarely. The carcinoma cells growth relatively
      slowly in comparison with brain cells which often overgrow the tumor cells in
      early passages. The origin of these rapidly dividing brain cells in carcinoma
      cultures is discussed with respect to the previous studies on adult human brain
      tissue cultures. It was found that the majority of cells in adult human brain
      cultures derived from brain biopsies of patients with non-cancer diseases do not
      express glial markers. Based on the previous studies we suggest that they are
      glial precursor cells. The high proliferative capacity and non-glial phenotype of
      these brain cells may lead to the suggestion that they are of cancer origin. In
      this study the establishment and characterization of a new carcinoma cell line
      135-BCA is described. The tissue cultures were derived from brain metastasis of
      lung large cell carcinoma. The cell line is specific by the epithelial cell
      morphology and evident cytokeratins expression during the whole subcultivation.
      All tumor cells were strongly immunoreactive for vimentin and negative stained
      for glial fibrillary acidic protein (GFAP). The new cell line may prove of value
      in biological and therapeutic studies of lung cancer. In addition, the further
      comparative analysis may reveal the environmental influence of brain tissue on
      carcinoma cells.

PMID- 11949842
TI  - Expression of apoptosis-regulating proteins p53, Bcl-2, and Bax in primary
      resected esophageal squamous cell carcinoma.
AB  - Apoptosis plays a key role in the pathogenesis, aggressiveness, and therapy
      responsiveness of cancer. Proteins of the Bcl-2 family as well as p53 are
      important regulators of apoptosis. The present study retrospectively examines the
      expression of apoptosis-regulating proteins in primary resected esophageal
      squamous cell carcinoma (ESCC) and the correlation between the outcome of
      patients' treatment and the expression of the proteins. We used antibodies
      specific for the human p53, Bcl-2 and Bax proteins to examine the expression of
      these apoptosis-regulating proteins in 40 archival specimens of patients with
      primary resected esophageal squamous cell carcinoma. The overall expression of
      p53, Bcl-2, and Bax was 73%, 18%, and 100%, respectively. No significant
      correlations were found between the expression of p53, Bcl-2, and Bax. The
      expression of Bcl-2 had a negative influence on survival in this population of
      primary resected ESCC patients (p=0.03). But no differences in survival were
      observed in relation to the expression of p53 or Bax. In conclusion, Bcl-2
      expression may provide additional and prognostic information for the clinical
      course of the disease and therefore to be developed as a prognostic indicator for
      primary resected esophageal squamous cell carcinoma.

PMID- 11949843
TI  - Expression of p53 and bcl-2 proteins in acute leukemias: an immunocytochemical
      study.
AB  - We have analyzed by immunocytochemistry the p53 and Bcl-2 proteins expression in
      49 patients with B-ALL, T-ALL and AML at the time of initial diagnosis. The
      diagnosis was based on morphologic and cytochemical criteria and on
      immunophenotyping. To demonstrate the p53 protein expression, p53 specific mouse
      antihuman immunoreagent clone DO-1 that recognizes both wild and mutated p53
      protein was used. To detect Bcl-2 a monoclonal antibody that recognizes the 26-kD
      Bcl-2 protein was applied. For evaluation of both proteins a sensitive Immunotech
      detection kit based on peroxidase labeled streptavidin biotin reagent was
      utilized. The patients were divided according to the presence or absence of both,
      nuclear p53 and cytoplasmic Bcl-2 proteins. A relative low frequency of p53
      protein expression in B- and T-lineage acute lymphoblastic leukemia has been
      shown at diagnosis. In AML cases, the frequency of p53 expression was higher than
      that in ALL. Bcl-2 protein immunoreactivity has been found in the majority of
      acute leukemia patients. The marked heterogeneity in the percentage of p53 and
      Bcl-2 positive cells in individual patients was observed. Comparative analysis of
      the distinct acute leukemia subtypes according to the percentage of p53 and Bcl-2
      positive cells showed no significant differences except for p53 protein
      positivity in relation between T-ALL and AML cases. The samples from healthy
      subjects used as a control exhibited very low proportion of positively stained
      cells and significantly differed from p53 as well as Bcl-2 positive cases. p53
      and Bcl-2 positivity have not been significantly affected neither by age, sex nor
      WB C counts. Association between myeloid cells maturation and proportion of p53
      and Bcl-2 positive cells was observed. Noteworthy was the inverse relation
      between the higher proportion of p53 positive cells and low Bcl-2 positivity in
      some cases of acute leukemia. Although our preliminary results need to be
      confirmed in a larger group of patients, immunocytochemical analysis of p53 and
      Bcl-2 proteins, indicators of cell alterations, may help to identify risk
      patients requiring intensive therapy.

PMID- 11949844
TI  - A study on nitric oxide secretion by transplantable melanoma cell lines with
      regard to their spontaneous apoptosis.
AB  - In the study we investigated if there exists any correlation in the nitric oxide
      (NO) secretion by two types of melanoma cells of the same origin but differing in
      their biological properties and ability to undergo spontaneous apoptosis. Our
      results suggest that there exists an inverse correlation between the dynamics of
      NO secretion by cells of two melanoma lines and their ability to undergo
      spontaneous apoptosis.

PMID- 11949845
TI  - Polymerase chain reaction detection of cells carrying t(14;18) in bone marrow of
      patients with follicular and diffuse large B-cell lymphoma: the importance of
      analysis at diagnosis and significance of long-term follow-up.
AB  - The t(14;18) is the most frequent chromosomal aberration observed in follicular
      lymphoma (FL), and is less frequent in diffuse large cell lymphoma (DLCL). The
      bcl-2/IgH rearrangement constitutes good target for polymerase chain reaction
      (PCR) detection that allows to find out one tumor cell in 100,000 normal cells.
      The PCR assay was used to detect bcl-2-rearranged cells in blood and bone marrow
      (BM) in 63 previously untreated patients with DLCL and in 53 patients with FL.
      Twenty five FL patients (47%) and 9 DLCL patients (14%) had PCR-detectable
      lymphoma cells in BM and peripheral blood. Minimal residual disease (MRD) was
      evaluated in 17 FL and 5 DLCL patients undergoing first-line chemotherapy. Three
      DLCL patients (60%) but only 1 FL (6%) patient achieved molecular response (PCR
      negative status in BM). Two PCR bcl-2/IgH positive patients with FL were treated
      with rituximab (anti-CD20 antibody) and had no PCR-detectable lymphoma cells in
      BM after the therapy. Peripheral blood stem cells (PBSC) were harvested in 5 FL
      (1 PCR-negative) and in 2 DLCL (1 PCR-negative) patients. PCR-positive lymphoma
      cells contamined PBSC in all patients with BM PCR-positivity before harvesting.
      Five FL patients underwent autologous transplantation (AT). No bcl-2/IgH positive
      cells were detected in 4 patients (80%) at any point after AT. One patient
      achieved molecular response after rituximab treatment. All the patients are in CR
      6, 22, 30, 31 and 42 months respectively, after AT. On the other hand, 4 FL
      patients in clinical complete remission, but with persistent PCR positivity in BM
      relapsed with median of 21 months (interval, 14-28 months) from the end of a
      first-line chemotherapy. Thus, the results show that PCR detection of the bcl
      2/IgH rearrangement is a very useful method in evaluating the BM infiltration by
      lymphoma cells especially in the situation of MRD. Conventional chemotherapy did
      not eradicate bcl-2 positive cells in BM in most of lymphoma patients, but
      autologous transplantation or rituximab immunotherapy can induce molecular
      response in a significant proportion of them. Our results support the previous
      observations of the molecular response importance in view of better disease free
      and probably also overall survival.

PMID- 11949846
TI  - The role of palliative radiotherapy in locally advanced non-small cell lung
      cancer.
AB  - The aim of this study was to evaluate retrospectively the treatment results of
      non-small cell lung cancer (NSCLC) patients treated with palliative intent in
      Dokuz Eylul University Hospital, Radiation Oncology Department. One hundred and
      fifteen inoperable, non-metastatic and symptomatic NSCLC patients were treated
      with palliative radiotherapy (PRT) between July 1991 and May 2000. PRT was used
      in patients with low performance status, weight loss more than 10% within last 6
      months, secondary malignancies, co-morbid diseases and socio-economic problems.
      Parallelly opposed isocentric antero-posterior fields including both the
      parenchymal and mediastinal masses were used. 10-55 Gy total doses were delivered
      in 1-23 fractions with a median of 30 Gy. Nineteen patients received systemic
      chemotherapy before PRT. Survival analysis was made from the treatment beginning
      date, and subjective palliation rates were assessed according to clinical
      improvements in symptomatology evaluated 1-6 weeks after PRT. The median follow
      up time was 28 weeks (1-234 weeks). Totally, 245 disease-related symptoms were
      detected in 115 patients. Overall "improvement" in symptomatology was found to be
      90% (221/245) with a "near-total response" rate of 46% (113/245). Hemoptysis was
      the best palliated symptom. Median survival time was 30 weeks. Karnofsky
      performance status (KPS) (p=0.015), weight loss (p=0.0015), histologic tumor type
      (p=0.0024) and tumor size (p=0.02) were found to effect overall survival rates
      significantly in uni-variant analysis. Multi-variant analysis revealed
      statistically significant effect with histological tumor type and weight loss
      status. Only 16% of patients (3/19) showed partial and 5% (1/19) complete
      response to systemic treatment. Median survival time was 46 weeks in this group.
      In conclusion, this retrospective study of patients with poor prognostic factors
      confirms that PRT is an effective treatment modality in symptomatic locally
      advanced NSCLC patients resulting in 90% symptomatic improvement rate and a
      median survival of 30 weeks.

PMID- 11949847
TI  - Molten globule structures in milk proteins: implications for potential new
      structure-function relationships.
AB  - Recent advances in the field of protein chemistry have significantly enhanced our
      understanding of the possible intermediates that may occur during protein folding
      and unfolding. In particular, studies on alpha-lactalbumin have led to the theory
      that the molten globule state may be a possible intermediate in the folding of
      many proteins. The molten globule state is characterized by a somewhat compact
      structure, a higher degree of hydration and side chain flexibility, a significant
      amount of native secondary structure but little tertiary folds, and the ability
      to react with chaperones. Purified alpha(s1)- and kappa-caseins share many of
      these same properties; these caseins may thus occur naturally in a molten globule
      like state with defined, persistent structures. The caseins appear to have
      defined secondary structures and to proceed to quaternary structures without
      tertiary folds. This process may be explained, in part, by comparison with the
      architectural concepts of tensegrity. By taking advantage of this "new view" of
      protein folding, and applying these concepts to dairy proteins, it may be
      possible to generate new and useful forms of proteins for the food ingredient
      market.

PMID- 11949849
TI  - Microbial succession of Debaryomyces hansenii strains during the production of
      Danish surfaced-ripened cheeses.
AB  - Surface-ripened cheeses of the Danbo type were analyzed for the presence of
      yeasts with special emphasis on Debaryomyces hansenii. Samples were taken from
      pasteurized milk, brine, and inoculation slurries and from cheese surfaces during
      ripening at a Danish dairy. D. hansenii was found to be the dominant yeast
      species throughout the ripening period, whereas other yeast species such as
      Trichosporon spp., Rhodotorula spp., and Candida spp. were found in minor
      concentrations during early stages of cheese ripening. Mitochondrial DNA RFLP was
      used to show that several strains of D. hansenii were present from the onset of
      ripening. Thereafter, a microbial succession among the strains took place during
      the ripening. After 3 d of ripening, only one strain was found. This particular
      strain was found to be dominant in 16 additional batches of surface-ripened
      cheeses. We investigated the cause of the observed microbial succession by
      determining the variation in strains with regard to their ability to grow on
      lactate and at different pH and NaCl concentrations. The strains were shown to
      vary in their ability to grow on lactate. In a full factorial design at three
      levels with factor levels close to the actual levels on the cheese surface,
      differences in pH and NaCl tolerances were observed. The dominant strain was
      found to be better adapted than other strains to the environmental conditions
      existing in surface-ripened cheeses during production [e.g., lactate as the main
      carbon source, pH 5.5 to 6.0 and NaCl concentrations of 7 to 10% (wt/vol)].

PMID- 11949848
TI  - Formation of reconstituted casein micelles with human beta-caseins and bovine
      kappa-casein.
AB  - Human beta-casein (CN) is the major protein of the human milk casein fraction
      (approximately 80%) and exists in six calcium-sensitive forms, having zero to
      five organic phosphates per molecule. The major forms are the doubly
      phosphorylated (beta-CN-2P; approximately 30%) and the quadruply phosphorylated
      (beta-CN-4P; approximately 35%) forms. Although calcium-insensitive, kappa-CN is
      known for its role in preventing the precipitation of beta-CN in the presence of
      Ca+2, but it is not known how the different levels of phosphorylation may affect
      this. In the present investigation, turbidity, measured at 400 nm, was determined
      at increasing temperatures (4 up to 37 degrees C) for solutions of beta-CN-2P and
      beta-CN-4P (3 mg/ml in 0.02 M NaCl, 0.01 M imidazole, pH 7) individually and also
      mixed with bovine kappa-CN in 6/1 and 3/1 weight ratios of beta/kappa and
      containing 0, 5, and 10 mM Ca+2. The results indicate that the first step of
      micelle formation probably leads to polymers of limited size, the only complexes
      available to beta-CN-2P under most conditions. With beta-CN-4P, these polymers
      aggregate further to give reconstituted micelles, probably because of the ability
      to form crosslinks at this phosphorylation level. The formation of reconstituted
      micelles under various conditions of pH, Ca+2 concentration and kappa-CN content
      indicates that both hydrophobic interactions and Ca+2 bridges or crosslinks may
      contribute to protein aggregation and micelle building.

PMID- 11949850
TI  - Rapid determination of tetracycline in milk by FT-MIR and FT-NIR spectroscopy.
AB  - The feasibility of measuring tetracycline at the ppb levels in milk was
      investigated by Fourier transform mid-infrared (FT-MIR) and Fourier transform
      near-infrared (FT-NIR) spectroscopic techniques. Milk samples spiked with
      different concentrations of tetracycline were scanned using FT-MIR and FT-NIR
      spectroscopy. Suitable spectral wave number regions were selected for principal
      least square (PLS) regression models development. Prediction errors were high
      when the calibration model was developed using the wide range of tetracycline
      concentrations (4 to 2000 ppb) in milk. Maximum correlation coefficient (R2)
      value of about 0.89 was obtained for the validation models developed using
      different concentration ranges. Prediction errors were high for FT-NIR method.
      Results indicated that FT-MIR spectroscopy could be used for rapid detection of
      tetracycline hydrochloride residues in milk.

PMID- 11949851
TI  - Milk synthetic response of the bovine mammary gland to an increase in the local
      concentration of arterial glucose.
AB  - Concentrations of glucose in the external iliac artery feeding one udder half of
      14 midlactation Holstein cows were increased by infusion to test the following
      three hypotheses of mammary function: 1) that mammary glands control their blood
      supply to maintain intracellular energy balance, 2) that milk precursors are
      taken out of capillary blood according to mass action kinetics, and 3) that the
      rate of milk component synthesis is dependent on its precursor's uptake from
      blood. The first seven cows received 20 g/h glucose during 10 h of infusion.
      Arterial concentrations of glucose were locally increased by only 10%, and the
      iliac plasma flow was not affected by glucose infusion, so the next seven cows
      were given 90 g/h glucose. Quantitative predictions resulting from the hypotheses
      were that arterial plasma flow would decrease by 32% with 90 g/h glucose
      infusion, glucose uptakes would increase and acetate, fatty acid, and amino acid
      uptakes decrease, and milk protein and fat yields and percentages would decrease.
      Iliac plasma flow decreased 16%, half of what was predicted, which suggests that
      other regulatory processes besides blood flow control took part in the response.
      Acetate and fatty acid uptakes by the mammary glands were reduced as predicted
      because of the lower blood flow, but an unexpected depression in extraction of
      plasma triacylglycerol also contributed to the reduced fatty acid uptake. Milk
      fat and protein yields were not affected by the exogenous glucose, falsifying the
      third hypothesis that milk component secretion is a function of uptake of its
      precursor. Milk fat and protein percentages declined with glucose infusion
      because of increased lactose synthesis and secretion of water into milk.

PMID- 11949852
TI  - Short communication: Hepatic gene expression for gluconeogenic enzymes in
      lactating dairy cows treated with bovine somatotropin.
AB  - Eight lactating Holstein dairy cows (80 d in milk) were used to examine the
      effects of exogenous bovine somatotropin (bST) on hepatic contents of mRNA
      encoding pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK),
      and microsomal triglyceride transfer protein (MTP). Concentrations of bST in
      plasma were higher and milk production increased 20% in bST-treated cows. Liver
      samples from cows treated with bST had significantly higher total lipid contents
      than those from control cows. Although there were small numerical tendencies,
      neither triglyceride concentrations in liver nor nonesterified fatty acids
      (NEFA), beta-hydroxybutyrate (BHBA), or glucose in plasma differed significantly
      between bST-treated and control cows. Short-term bST treatment had no detectable
      effects on contents of PC, PEPCK, and MTP mRNA in the liver. In summary,
      exogenous bST stimulation of milk production is not mediated through enhanced
      liver gluconeogenesis, but may involve partitioning of glucose and fatty acids
      for preferential use by the mammary gland.

PMID- 11949854
TI  - Transport of colostral macromolecules into the cerebrospinal fluid via plasma in
      newborn calves.
AB  - The objective of this study was to investigate the transfer of bovine colostral
      macromolecules especially the lactoferrin (Lf), transferrin (Tf), immunoglobulin
      G (IgG), and epidermal growth factor (EGF) from the gastrointestinal tract to the
      cerebrospinal fluid (CSF) via systemic circulation in newborn calves. Cannulae
      were placed into the jugular vein and cisterna magna to collect blood and CSF,
      respectively at various time points. The colostrum, plasma, and CSF were analyzed
      by ELISA, SDS-PAGE, two-dimensional PAGE, and Western blotting. The concentration
      of total protein, Lf, Tf, and IgG in plasma averaged 47 mg, 204 ng, 101 microg
      and 15 microg/ml before colostrum feeding and increased to the peak values of 64
      mg, 2413 ng, 820 microg, and 4608 microg/ml 8 h after feeding, respectively.
      Before colostral feeding CSF, total protein, Lf, Tf, and IgG averaged 0.44 mg,
      10.3 ng, 0.31 microg, and 0.11 microg/ml, but peak values after feeding averaged
      2.0 mg, 173 ng, 71 microg and 72 microg/ml after 10 h, respectively.
      Immunologically, six EGF-positive protein bands were detected in colostrum as
      well as in three bands higher density in plasma and CSF after colostral feeding.
      This study revealed that the colostral macromolecules were not only absorbed into
      the systemic circulation, but also some of them including Lf, Tf, IgG, and EGF
      like proteins were transported into the CSF in a time-dependent manner through
      blood-CSF or blood-brain barrier of the newborn calves.

PMID- 11949853
TI  - Role of prolactin, growth hormone and insulin-like growth factor 1 in mammary
      gland involution in the dairy cow.
AB  - Bovine mammary involution, an important process for subsequent lactations, is
      characterized by loss of epithelial cells by apoptosis, but its hormonal
      regulation is still not well defined. Prolactin (PRL) and growth hormone (GH)
      play a specific role on rat mammary gland apoptosis, through insulin-like growth
      factor 1 (IGF-1) and the IGF binding protein (IGFBP) system. The purpose of our
      investigation was to determine the possible role of PRL, GH, and IGF-1 on cell
      survival and on IGFBP-5 expression in the bovine mammary gland. Mammary gland
      explants were cultured in the presence of cortisol, 17beta-estradiol,
      progesterone, insulin, PRL, GH, and IGF-1 and with the same treatment but without
      PRL, GH or IGF-1, respectively. After 24 h of culture, we determined the level of
      apoptosis through evaluation of DNA laddering in the oligonucleosomal fraction
      and examined IGFBP-5 messenger RNA (mRNA) expression. The results show a high
      level of DNA laddering and an increase in IGFBP-5 mRNA content in mammary
      explants cultured in the absence of PRL, GH, or IGF-I with respect to explants
      treated with all hormones. Moreover, explants cultured in presence of PRL, GH, or
      IGF-I show a low level of DNA laddering and IGFBP-5 expression with respect to
      explants cultured without any hormones. These data demonstrate a relationship
      between levels of apoptosis and IGFBP-5 mRNA expression in the bovine mammary
      gland and confirm the involvement of this binding protein programmed cell death
      and its relationship with the main lactogenic hormones.

PMID- 11949855
TI  - Relationships between fecal culture, ELISA, and bulk tank milk test results for
      Johne's disease in US dairy herds.
AB  - Objectives were to estimate percentages of seropositive herds with cows shedding
      Mycobacterium paratuberculosis in feces and milk, and to estimate sensitivity,
      specificity, and predictive value of an ELISA relative to fecal culture. Dairy
      cows (n = 712) were randomly selected from 61 herds previously identified by
      ELISA as positive for Johne's disease. Fecal and bulk tank milk samples (n = 52
      of 61 herds) were obtained from 10 states in the United States. Fecal samples
      were processed by a double centrifugation, double decontamination culture
      procedure. Milk samples were processed for both culture and DNA analysis by using
      polymerase chain reaction (PCR). Of 24 herds with at least three cows that had
      tested ELISA-positive, 79% were also culture-positive, compared with 18 of 37
      herds with one or two ELISA-positive cows. Both fecal-culture and ELISA results
      were available on 651 cows; only 25% of cows that were fecal-culture positive
      also tested positive by ELISA and over 6% of cows that were fecal-culture
      negative tested ELISA-positive. Milk samples all cultured negative, but analysis
      of milk samples by PCR resulted in 68% of herds positive for M. paratuberculosis
      DNA including 24 of 31 herds with positive fecal cultures and 11 of 21 herds with
      negative fecal cultures. Sensitivity and specificity of the ELISA compared with
      fecal culture is lower than previously reported and perhaps best used in
      screening herds because of limited efficacy to predict infection in individual
      cows. In addition, contamination of bulk tank milk samples with M.
      paratuberculosis does occur in seropositive herds, even in some with negative
      fecal cultures.

PMID- 11949856
TI  - Frequencies of injection-site lesions in muscles from rounds of dairy and beef
      cow carcasses.
AB  - The frequency of injection-site lesions in muscles from top sirloins and rounds
      in fed cattle carcasses is well documented; this study characterizes the
      frequency and severity of lesions in muscles from rounds of beef and dairy cow
      carcasses. Audits were conducted in 1998, 1999, and 2000 on 3190 rounds from cow
      carcasses. Outside round muscles were cut into 1.25-cm slices to characterize
      lesions. In 1998, 31% of beef rounds and 60% of dairy rounds had an injection
      site lesion. Frequency of lesions in beef rounds significantly declined 5
      percentage points between 1998 and 1999 and 6 percentage points between 1999 and
      2000. The frequency of lesions in dairy rounds significantly declined 9
      percentage points between 1998 and 1999 and 16 percentage points between 1999 and
      2000. Frequencies of injection-site lesions in muscles of beef rounds were
      significantly lower than those in muscles of dairy rounds in all 3 yr. Injection
      site lesions were most common between the hooks and pins of the hindquarter of
      beef cattle and between the pins and hocks of the hindquarter of dairy cattle.
      Clear lesions and woody calluses exceeded 89% and occurred more frequently than
      did other kinds of lesions in muscles of beef and dairy rounds in 1998, 1999, and
      2000 audits. Of all injection-site lesions, between 3 and 5% were cystic in
      muscles of beef rounds, similar to the 2 to 4% of cystic lesions found in muscles
      of dairy rounds. Although yearly data indicate trends in declining frequencies of
      injection-site lesions, the need remains for educational programs and continued
      improvements in beef quality assurance practices among both beef and dairy
      producers.

PMID- 11949857
TI  - Bovine somatotropin attenuates phorbol ester-induced prostaglandin F2alpha
      production in bovine endometrial cells.
AB  - The recent observation that bovine somatotropin (bST) treatment at a timed
      insemination improves pregnancy rates in lactating dairy cows raises the
      possibility that growth hormone (GH) may modulate the endocrine and biochemical
      cross talk between the conceptus and maternal uterus at the time of pregnancy
      establishment in cattle. The objective of this study was to characterize the
      cellular and molecular mechanisms by which exogenous GH affects phorbol ester
      induced prostaglandin F2alpha (PGF2alpha) production in cultured bovine
      endometrial (BEND) cells. Serum-deprived BEND cells were incubated with or
      without recombinant bovine GH (rbGH), insulin-like growth factor (IGF)-I,
      recombinant bovine interferon (rbIFN)-tau or a combination of rbGH + rbIFN-tau
      for 3 h and then treated with phorbol 12,13-dibutyrate (PDBu) for an additional 6
      h. Exogenous PDBu increased PGF2alpha secretion and steady-state levels of COX-2
      mRNA within 3 h. Priming of BEND cells with rbGH reduced PGF2alpha response to
      PDBu, whereas cotreatment with IGF-I amplified PDBu induction of PGF2alpha.
      Preincubation of cell monolayers with rbIFN-tau suppressed PGF2alpha and COX-2
      mRNA responses to PDBu. Inhibitory effects of rbGH and rbIFN-tau on PDBu-induced
      PGF2alpha production were additive. Results provide the first direct evidence
      that supplemental bST may interact with conceptus-secreted IFN-tau to modulate
      PGF2alpha secretion at the critical time of maternal recognition of pregnancy.

PMID- 11949858
TI  - Decreased neutrophil function as a cause of retained placenta in dairy cattle.
AB  - It is unclear why some cows fail to expel the placenta following calving. One
      theory suggests the fetal placenta must be recognized as "foreign" tissue and
      rejected by the immune system after parturition to cause expulsion of the
      placenta. We hypothesized that impaired neutrophil function causes retained
      placenta (RP). We examined the ability of neutrophils to recognize fetal
      cotyledon tissue as assessed by a chemotaxis assay, which utilized a placental
      homogenate obtained from a spontaneously expelled placenta as the
      chemoattractant. Neutrophil killing ability was also estimated by determining
      myeloperoxidase activity in isolated neutrophils. Blood samples were obtained
      from 142 periparturient dairy cattle in two herds. Twenty cattle developed RP
      (14.1%). Neutrophils isolated from blood of cows with RP had significantly lower
      neutrophil function in both assays before calving, and this impaired function
      lasted for 1 to 2 wk after parturition. The addition of antibody directed against
      interleukin-8 (IL-8) to the cotyledon preparation used as a chemoattractant
      inhibited chemotaxis by 41%, suggesting that one of the chemoattractants present
      in the cotyledon at parturition is IL-8. At calving, plasma IL-8 concentration
      was lower in RP cows (51 +/- 12 pg/ml) than in cows expelling the placenta
      normally (134 +/- 11 pg/ml). From these data, we suggest that neutrophil function
      is a determining factor for the development of RP in dairy cattle. Also,
      depressed production of IL-8 may be a factor affecting neutrophil function in
      cows developing RP.

PMID- 11949860
TI  - Protective effect of melatonin and catalase in bovine neutrophil-induced model of
      mammary cell damage.
AB  - The effect of several antioxidants and a proteinase inhibitor on bovine
      neutrophil-induced mammary epithelial cell damage was investigated using an in
      vitro model of co-culturing bovine neutrophils and MAC-T cells, a mammary
      epithelial cell line. Epithelial cell damages were evaluated by measuring lactate
      dehydrogenase activity in culture media and by morphological observations of
      cells after acridine orange staining. Activation of neutrophils with Escherichia
      coli lipopolysaccharide and phorbol 12-myristate 13-acetate caused superoxide and
      gelatinase release in media. Activated neutrophils damaged the epithelial cells,
      as demonstrated by an increase in lactate dehydrogenase release and the
      observation of morphological changes. The addition of melatonin or catalase
      reduced neutrophil-induced cytotoxicity in a dose-dependent manner, whereas
      superoxide dismutase and aprotinin had no effect on cytotoxicity. Melatonin has
      been reported to scavenge hydroxyl radical and peroxynitrite, whereas catalase
      and superoxide dismutase scavenge hydrogen peroxide and superoxide, respectively.
      Our results suggest that hydroxyl radicals released by activated bovine
      neutrophils cause damage to mammary epithelial cells and that antioxidants may be
      useful to protect the mammary tissue during bovine mastitis.

PMID- 11949859
TI  - Evaluation of the efficacy of an internal teat sealer during the dry period.
AB  - The efficacy of an internal dry period teat sealer containing bismuth subnitrate
      (Product A; Teatseal, Cross Vetpharm Group Ltd, Ireland) was compared with a long
      acting antibiotic preparation containing cephalonium (Product B; Cepravin Dry
      Cow, Schering-Plough Ltd, UK), by assessing the number of new intramammary
      infections (IMI) acquired during the dry period and the number of cases of
      clinical mastitis during the first 100 d of lactation. Selection of study animals
      was based on historical data. No cases of clinical mastitis and all routine cow
      level somatic cell counts <200,000 cells/ml during the previous lactation were
      used to select cows likely to be uninfected with a major pathogen at drying off.
      Compared with the antibiotic tube, quarters that received the teat sealer
      acquired significantly fewer new IMI caused by Escherichia coli, all
      Enterobacteriaceae, and all major pathogens combined. There was no significant
      differences in the number of IMI caused by any other major pathogen. There was no
      significant difference in the severity or number of quarter or cow cases of
      clinical mastitis between product groups. Sixty quarters (3.2%) were infected
      with major pathogens at drying off, 27 (2.9%) in teat sealer and 33 (3.5%) in
      antibiotic tube cows. The dry period cure rate was not significantly different
      (63% product A, 70% product B). This is the first controlled study to demonstrate
      the efficacy of an internal bismuth teat sealer in protecting quarters against
      new dry period IMI caused by major mastitis pathogens, particularly environmental
      organisms, under UK field conditions.

PMID- 11949861
TI  - Short communication: Effect of subacute ruminal acidosis on in situ fiber
      digestion in lactating dairy cows.
AB  - Subacute ruminal acidosis (SARA) was induced by replacing 25% of the total mixed
      ration intake [dry matter (DM) basis] with pellets consisting of 50% wheat and
      50% barley. This reduced dietary forage content (DM basis) from 39.7 to 29.8% and
      increased the dietary concentrate content from 60.3 to 70.2%. Induction of SARA
      reduced the 24- and 48-h in situ neutral detergent fiber (NDF) degradabilities of
      grass hay numerically from 31.5% to 24.6% (P = 0.29) and from 51.3% to 36.9% (P <
      0.05), respectively. The 24- and 48-h in situ NDF degradabilities of legume hay
      were reduced from 35.3 to 26.3% (P < 0.05) and from 49.0 to 35.8% (P < 0.05),
      respectively. The 24- and 48-h in situ NDF degradabilities of corn silage were
      reduced from 44.0 to 37.2% (P < 0.05) and from 56.1 to 44.8% (P < 0.05),
      respectively. This study suggests that induction of SARA by excess feeding of
      wheat/barley pellets reduces the rumen digestion of NDF from grass hay, legume
      hay, and corn silage.

PMID- 11949862
TI  - Effects of pH and pH fluctuations on microbial fermentation and nutrient flow
      from a dual-flow continuous culture system.
AB  - Eight dual-flow continuous culture fermenters (1400 ml) were used in two
      consecutive periods to study the effects of pH and pH fluctuations on microbial
      fermentation and nutrient flow. Fermenters were maintained at 39 degrees C, with
      solid and liquid dilution rates of 5 and 10%/h, respectively, and fed
      continuously a 60% alfalfa hay and 40% concentrate diet (18.9% crude protein,
      36.6% neutral detergent fiber, 17.6% acid detergent fiber). Treatments were high
      pH (constant at 6.4); low pH (constant at 5.7); cycles of 4 h at pH 6.4 and 4 h
      at pH 5.7; and pH constant at 6.4, except for two 30-min drops per day to pH 5.7,
      followed by a 3-h slow recovery to pH 6.4. The low pH (constant at 5.7) produced
      lower apparent dry matter, neutral detergent fiber and acid detergent fiber
      digestion, lower total and branch-chained volatile fatty acid concentrations, and
      lower acetate and higher propionate proportions than high pH (constant at 6.4).
      There were no differences in these estimates between constant high pH and the two
      treatments that alternated high pH and low pH. The constant low pH reduced
      protein degradation and increased nonammonia N and dietary N flow compared with
      constant high pH. The pH treatments had no effect on bacterial N flow or
      efficiency of microbial protein synthesis. Flow of essential amino acids was
      highest for constant low pH and lowest for constant high pH. Results indicate
      that constant low pH reduced fiber and protein digestion and increased the flow
      of total and some individual amino acids. However, the effects of transitory
      decreases of pH were either small or insignificant with the conditions tested in
      this study.

PMID- 11949863
TI  - Supplementation with partially hydrogenated oil in grazing dairy cows in early
      lactation.
AB  - Effects of partially hydrogenated oil on performance, loss of body weight and
      body condition score, and blood metabolite and hormone concentrations were
      evaluated in 37 multiparous Holstein cows in grazing conditions during the first
      100 d of lactation. Six additional Holstein cows, each fitted with a ruminal
      cannula, were allocated to a replicated 3 x 3 Latin square to evaluate effects of
      supplemental fat on rumen environment and pasture digestion. All cows grazed
      mixed pastures based on alfalfa (Medicago sativa) and orchardgrass (Dactylis
      glomerata L.) and received 5.4 kg/d of a basal concentrate to which 0, 0.5, or 1
      kg/cow per day of partially hydrogenated oil (melting point 58 to 60 degrees C)
      containing 30.3, 34.9, 21.8, and 3.3% of C16:0, C18:0, C18:1, and C182,
      respectively, was added. Feeding 1 kg/d of supplemental fat increased fat
      corrected milk from 23.4 to 26.3 kg/d, milk fat content from 3.44 to 3.78%, and
      milk fat yield from 0.87 to 1.03 kg/d compared to control. Milk protein
      percentage and yield were not affected. Cows fed 1 kg/d of fat increased the
      content and yield of C16:0 and C18:0 in milk compared with cows fed no added oil.
      Dry matter intake (DMI) from pasture decreased from 17.8 kg/d for control cows to
      13.6 kg/d for cows fed 1 kg of oil, whereas DMI from concentrate was higher for
      cows fed 1 kg/d of fat (6.0 kg/d) than for controls (5.2 kg/d). Supplemental fat
      did not affect total dry matter or estimated energy intake and did not change
      losses of body weight or body condition scores. Plasma concentrations of
      nonesterified fatty acids, insulin, somatotrophin, and insulin-like growth factor
      I did not differ among treatments. Concentration of plasma triglycerides was
      lowered from 318.5 to 271.2 mg/dl, whereas plasma cholesterol was elevated from
      185.0 to 235.8 mg/dl in cows receiving 1 kg/d of supplemental fat compared with
      controls. Responses to lipolytic or insulin challenges were not affected by
      feeding oil. Supplemental fat did not affect the digestion of pasture fiber. The
      addition of energy in the form of partially hydrogenated fat to early lactation
      dairy cows fed primarily on pasture increased the yield of fat-corrected milk and
      milk fat content when it represented about 11% of the total metabolizable energy
      requirement of cows, without affecting milk protein content. The partial
      hydrogenation of a byproduct of the oil industry apparently prevented detrimental
      effects of fat supplementation on ruminal digestion.

PMID- 11949864
TI  - Duodenal glucose increases glucose fluxes and lactose synthesis in grass silage
      fed dairy cows.
AB  - The effect of intestinal glucose supply on whole body rate of glucose appearance
      (WBGRa) and mammary utilization of glucose was studied in four lactating dairy
      cows. Glucose (0, 443, 963 and 2398 g/d) was continuously infused in the duodenum
      over 14-d periods using a Latin square design. A grass silage-based diet was
      formulated so that treatments were isoenergetic and isonitrogenous and contained
      100 and 110% of energy and protein requirements according to INRA (1989). The
      WBGRa was measured by the [6,6-(2)H2]glucose dilution technique, and mammary
      glucose balance by arteriovenous differences and blood flow measurements.
      Duodenal glucose infusion increased arterial glucose concentrations linearly,
      whereas arterial concentrations of insulin, growth hormone, and glucagon were not
      changed. The WBGRa increased linearly with increasing glucose loads. The increase
      represented 42% of the intestinal glucose supplement. Mammary blood flow
      dramatically increased (up to 45%) and was associated with a significant increase
      of arterial insulin-like growth factor-1 concentrations. Mammary gland rate of
      glucose disappearance ([6,6-(2)H2]glucose measurement) increased linearly,
      whereas net mammary balance of glucose, lactose, and milk yields increased
      quadratically. Net mammary balance of glucose accounted for 60% of WBGRa, except
      for the greatest dose (47.6%). The decrease in milk yield with 2398 g/d of
      glucose may be explained by an imbalance in intracellular intermediate
      concentrations. The milk ratio of glucose-1-phosphate to glucose-6-phosphate
      decreased significantly at the greatest infusion of glucose. In conclusion,
      exogenous glucose supply to a grass silage-based diet increased WBGRa, mammary
      utilization of glucose and milk synthesis.

PMID- 11949865
TI  - Effect of feeding a corn hybrid selected for leafiness as silage or grain to
      lactating dairy cattle.
AB  - A leafy corn hybrid was compared to a grain corn hybrid as silage and high
      moisture grain to evaluate dry matter intake, milk yield, and milk composition.
      Sixteen multiparous Holstein cows averaging 97 DIM were used in a feeding trial
      based on 4 x 4 Latin squares with 21-d periods. Each of four diets contained (dry
      basis) 8% chopped hay, 42% corn silage, 11% high moisture corn grain, 10% whole,
      fuzzy cottonseed, and 29% protein concentrate. One diet used leafy corn as both
      high moisture grain and silage. A second diet contained grain corn hybrid
      (control) as both high moisture grain and silage. A third diet contained leafy
      corn for high moisture grain and control corn for silage and the fourth diet used
      control corn for high moisture grain and leafy corn for silage. Cows fed diets
      containing leafy silage produced more milk and milk protein and ate more DM than
      cows fed control silage. The corn hybrid used for high moisture grain did not
      influence milk yield or composition. Dry matter intake was greater for cows fed
      the diet containing both leafy high moisture grain and leafy silage than for cows
      fed both control high moisture grain and control silage, but milk yield and
      composition were not different. When fed as silage, the leafy corn hybrid used in
      this experiment supported greater DMI as well as higher milk and protein yields
      when compared to the grain corn hybrid.

PMID- 11949866
TI  - Processing and chop length effects in brown-midrib corn silage on intake,
      digestion, and milk production by dairy cows.
AB  - In this experiment, we evaluated the influence of increasing chop length and
      mechanical processing of whole-plant brown-midrib corn silage on intake,
      digestion, and milk production by dairy cows. Corn silage treatments were
      harvested at three-quarter milk line stage of maturity at 13- and 19-mm
      theoretical chop length without processing, or at 19- and 32-mm theoretical chop
      length with processing at a 2-mm roll clearance. Twenty-four multiparous Holstein
      cows that averaged 102 +/- 17 d in milk at trial initiation were randomly
      assigned to treatments in a replicated 4 x 4 Latin square design with 28-d
      periods. Preplanned orthogonal contrasts were used to evaluate effects of
      processing (19 processed vs. 19 mm unprocessed) and chop length (13 vs. 19 mm
      unprocessed and 19 vs. 32 mm processed). Treatments were fed in total mixed
      rations containing 60% forage (67% corn silage and 33% alfalfa silage) and 40%
      shelled corn and soybean meal-based concentrate (dry matter basis). Milk yield
      was unaffected by treatment. Dry matter intake was unaffected by corn silage
      processing, but increasing corn silage chop length reduced dry matter intake in
      unprocessed (26.6 vs. 25.5 kg/d) and processed (25.9 vs. 25.1 kg/d) chop length
      contrasts. Processing reduced milk fat content (3.36 vs. 3.11%) and yield (1.43
      vs. 1.35 kg/d), increased total-tract starch digestion (92.9 vs. 97.4%), and
      decreased total-tract neutral detergent fiber digestion (51.0 vs. 41.8%). Total
      chewing time (min/d) was unaffected by treatment. Masticate mean particle length
      was unaffected by chop length in unprocessed and processed corn silage
      treatments. In this study with brown-midrib corn silage fed to dairy cows
      producing 43 kg/d of milk, there were no benefits from crop processing or
      increasing chop length on lactation performance.

PMID- 11949867
TI  - Feeding fish meal and extruded soybeans enhances the conjugated linoleic acid
      (CLA) content of milk.
AB  - Twelve multiparous Holstein cows averaging 65 (33 to 122) DIM were used in a 4 x
      4 Latin square for 4-wk periods to determine whether feeding fish oil as fish
      meal would stimulate increased amounts of milk conjugated linoleic acid (cis-9,
      trans-11 C18:2; CLA) and transvaccenic acid (trans-11 C18:1; TVA) when the cows
      were fed extruded soybeans to supply additional linoleic acid. Treatment diets
      were 1) control; 2) 0.5% fish oil from fish meal; 3) 2.5% soybean oil from
      extruded soybeans; and 4) 0.5% fish oil from fish meal and 2% soybean oil from
      extruded soybeans. Diets were formulated to contain 18% crude protein and were
      composed (dry basis) of 50% concentrate mix, 25% corn silage, and 25% alfalfa
      hay. Intake of DM was not affected by diet. Milk production was increased by
      diets 2, 3, and 4 compared with diet 1 (control). Milk fat and milk protein
      percentages decreased with diets 3 and 4. Milk fat yield was not affected by
      treatments, but yield of milk protein was increased with supplemental fish meal
      and extruded soybeans or their blend. When diets 2, 3, or 4 were fed,
      concentrations of cis-9, trans-11 CLA in milk fat increased by 0.4-, 1.4-, and
      3.2-fold, and TVA concentrations in milk fat increased by 0.4-, 1.8-, and 3.5
      fold compared with the control milk fat. Increases in TVA and cis-9, trans-11 CLA
      were 91 to 109% greater when a blend of fish meal and extruded soybeans was fed
      than the additive effect of fish meal and extruded soybeans. This suggested that
      fish oil increased the production of CLA and TVA from other dietary sources of
      linoleic acid such as extruded soybeans.

PMID- 11949868
TI  - Effect of supplemental tallow on performance of dairy cows fed diets with
      different corn silage:alfalfa silage ratios.
AB  - A study was conducted to investigate the response to supplemental tallow of
      lactating cows fed basal diets with different alfalfa silage:corn silage ratios.
      We postulated that supplemental tallow will have decreasing negative effects on
      rumen fermentation, dry matter intake (DMI), and milk fat percentage as the
      dietary ratio of alfalfa silage:corn silage is increased. Eighteen Holstein cows
      averaging 134 +/- 14 d in milk were used in a replicated 6 x 6 Latin square
      design with 21-d periods. Treatments were arranged as a 2 x 3 factorial with 0 or
      2% tallow (DM basis) and three forage treatments: 1) 50% of diet DM as corn
      silage, 2) 37.5% corn silage and 12.5% alfalfa silage, and 3) 25% corn silage and
      25% alfalfa silage. Cows were allowed ad libitum consumption of a total mixed
      ration. Diets were formulated to contain 18% crude protein and 32% neutral
      detergent fiber. No fat x forage treatment interactions were observed. Fat
      supplemented cows had lower DMI and produced more milk with less milk fat content
      relative to non-supplemented cows. Concentration of trans-octadecenoic acids was
      higher in milk fat of tallow-supplemented cows. Tallow supplementation had no
      effect on ruminal pH and acetate:propionate ratio, but tended to decrease total
      volatile fatty acid (VFA) concentration in the rumen. Increasing the proportion
      of alfalfa silage increased DMI, milk fat percentage, and milk fat yield
      regardless of the fat content of the diet. Total VFA concentration and
      acetate:propionate ratio in the rumen were increased in response to higher levels
      of alfalfa in the diets. These results suggest that replacing corn silage with
      alfalfa silage did not alleviate the negative response of dairy cows to tallow
      supplementation at 2% of diet DM.

PMID- 11949869
TI  - Inhibition of fatty acid synthesis in bovine mammary homogenate by palmitic acid
      is not a detergent effect.
AB  - Supplemental fat fed to dairy cows affects the fat composition of milk by
      reducing the yield of mammary synthesized fatty acids. The effect has been
      attributed to a potential allosteric inhibition of acetyl coenzyme-A, a key
      enzyme in fatty acid synthesis. In vitro experiments have demonstrated an
      inhibition of fatty acid synthesis when long-chain fatty acids are added to
      incubations. However, in vitro inhibition can result from a nonspecific detergent
      effect arising from an inherent physical property of fatty acids. An allosteric
      role for palmitic acid has not been tested in bovine mammary tissue. The
      objective of this experiment was to test the hypothesis that palmitic acid is an
      allosteric inhibitor of fatty acid synthesis in mammary tissue. We tested for a
      detergent effect by including a synthetic detergent, sodium dodecyl sulfate,
      under identical incubation conditions. A subcellular supernatant fraction of
      mammary tissue was used for incubations in the present experiment. The incubation
      system produced free fatty acids in a linear fashion for time and protein
      content. Results indicated that fatty acid synthesis was affected by the addition
      of palmitic acid to the incubations but not by caprylic acid, a short-chain fatty
      acid. Sodium dodecyl sulfate did not affect fatty acid synthesis at the
      concentrations used. The results of the present experiment indicate that palmitic
      acid inhibited fatty acid synthesis, and the effect was not the result of a
      detergent effect.

PMID- 11949870
TI  - The effect of ruminal fluid preparations on the growth and health of newborn,
      milk-fed dairy calves.
AB  - The objective of this study was to determine the effect of oral doses of ruminal
      fluid (RF) on the growth and health of newborn, milk-fed heifer dairy calves (0
      to 6 wk of age). Calves given 8 ml of RF each day until weaning gained more
      weight and had fewer scours than controls that did not receive RF. Because RF
      that was exposed to oxygen or was autoclaved also gave a response, it is unlikely
      that the preparations were acting as a probiotic. When the RF was centrifuged to
      separate the cells (RFC) from the fluid (RFS), both fractions had similar
      activity, and this result indicated that the response was not nutritional; that
      is, 1) RFC supplied a small amount of protein (approximately 8 mg/d), but RFS had
      much less protein, and 2) RFS had volatile fatty acid, but RFC had little if any
      volatile fatty acid. However, both RFS and RFC had bacterial polysaccharide, and
      bacterial polysaccharide has strong antigenic properties. In the first three
      studies, treated calves were given RF preparations each day until weaning (6 wk),
      but a subsequent experiment indicated that calves given autoclaved RF for only 5
      d (d 1 to 5) also had greater body weight gains during the first 2 wk of life and
      fewer scours than untreated controls. Given that the dosage of RF was small and
      the material could be autoclaved to prevent disease transmission, RF
      supplementation could be a practical tool for improving calf health.

PMID- 11949871
TI  - Beneficial effect of goat milk on nutritive utilization of iron and copper in
      malabsorption syndrome.
AB  - The search for diets that improve the digestive and metabolic use of iron and
      copper in malabsorption syndrome led us to study goat milk for particular
      nutritional characteristics and compare it with cow milk, which is usually
      supplied. We studied the metabolism of iron and copper in transected rats
      (control) and in resected rats (resection of 50% of the distal small intestine).
      The diets used were the standard diet recommended by the American Institute of
      Nutrition and diets based on goat or cow milk. Intestinal resection reduced the
      apparent digestibility coefficient (ADC) of iron in the three diets tested. In
      the transected and resected rats, the ADC of iron was highest with the goat milk
      diet, followed by the standard diet and lowest with the cow milk diet. The ADC of
      copper was not affected by intestinal resection in the animals fed the goat milk
      diet, and was higher than that in the two groups of animals fed the other diets.
      Intestinal resection reduced the ADC of copper with the standard diet and the cow
      milk diet. When both groups of animals were fed the goat milk diet, the deposit
      of iron in the organs was greater than with those fed the cow milk diet and
      similar to that in those animals given the standard diet. The copper content in
      the kidneys was lower in the resected than in the transected animals, except in
      the case of those fed the goat milk diet, in which it was similar to that of the
      control (transected) rats. This study shows the beneficial effect of goat milk,
      with respect to cow milk, on the metabolism of iron and copper in control rats,
      especially those with malabsorption syndrome.

PMID- 11949872
TI  - Proven and young Holstein bulls compared for daughter yields, productive life,
      somatic cell score, and inbreeding.
AB  - The objective of this study was to compare daughters of proven (progeny-tested)
      and young sampling bulls available for use at the same time for yield traits,
      productive life, somatic cell score, and inbreeding. Data were from USDA sire
      evaluations of July 1989 through July 1994. Proven bulls used between 1989 and
      1994 were identified based on the change in number of daughters. Young bulls were
      identified based on age and date a bull first entered artificial insemination.
      Young bulls were classified into two categories: one included all young bulls
      available in one year and the other included the top 50% on parent average for
      milk. Daughter deviations for yields, productive life and somatic cell scores,
      and average inbreeding were obtained from May 2000 evaluation. Daughter deviation
      milk was not different between proven and top 50% young bulls but was lower for
      all young bulls. Young bulls (all and top 50%) exceeded proven bulls in daughter
      deviation fat and protein. Progeny of proven bulls had favorably higher
      productive life in most years but unfavorably higher somatic cell score than
      progeny of young bulls. Inbreeding was consistently higher for daughters of young
      bulls than for those of proven bulls. Results indicate that young bulls were
      competitive with proven bulls. Use of young bulls from among the top 50% should
      result in equal or higher genetic progress in yields compared to contemporaries
      by proven bulls.

PMID- 11949873
TI  - Prediction of most recent evaluations of Holstein bulls from first available
      pedigree information.
AB  - The objectives of this study were to predict most recent evaluations of young
      bulls entering artificial insemination (AI) sampling programs from pedigree
      information available at time of sampling and investigate whether prediction
      equations differ among AI organizations. Data were pedigree information and most
      recent USDA evaluations on bulls entering AI sampling programs from 1989 through
      1994. Pedigree information included earliest available parent average, predicted
      transmitting abilities (PTA) of sire, dam, and maternal grand sire. Most recent
      evaluations were from May 2000 evaluations and included PTA and daughter yield
      deviations for milk, fat, and protein. Regression coefficients on PTA of sire and
      PTA of dam were less than the expected coefficient of 0.50. Accuracy of
      prediction as determined by R-square values was less than 12%. Inclusion of PTA
      of maternal grand sire after PTA of sire and dam increased the accuracy of
      prediction by less than 1%, but regression coefficients on PTA of maternal grand
      sire differed from 0. Regressions on parent average were not different among AI
      organizations for prediction of PTA and daughter yield deviations. Partial
      regression coefficients on PTA of sire differed among AI organizations for
      prediction of fat and protein but did not differ for milk. Coefficients on PTA of
      dam did not differ among organizations. These results indicate that AI
      organizations put different emphasis on PTA of sire in selection of sons for fat
      and protein.

PMID- 11949875
TI  - Estimating daily fat yield from a single milking on test day for herds with a
      robotic milking system.
AB  - The objective of this study was to estimate the daily fat yield and fat
      percentage from one sampled milking per cow per test day in an automatic milking
      system herd, when the milking times and milk yields of all individual milkings
      are recorded by the automatic milking system. Multiple regression models were
      used to estimate the 24-h fat percentage when only one milking is sampled for
      components and milk yields and milking times are known for all milkings in the 24
      h period before the sampled milking. In total, 10,697 cow test day records, from
      595 herd tests at 91 Dutch herds milked with an automatic milking system, were
      used. The best model to predict 24-h fat percentage included fat percentage,
      protein percentage, milk yield and milking interval of the sampled milking, milk
      yield, and milking interval of the preceding milking, and the interaction between
      milking interval and the ratio of fat and protein percentage of the sampled
      milking. This model gave a standard deviation of the prediction error (SE) for 24
      h fat percentage of 0.321 and a correlation between the predicted and actual 24-h
      fat percentage of 0.910. For the 24-h fat yield, we found SE = 90 g and
      correlation = 0.967. This precision is slightly better than that of present a.m.
      p.m. testing schemes. Extra attention must be paid to correctly matching the
      sample jars and the milkings. Furthermore, milkings with an interval of less than
      4 h must be excluded from sampling as well as milkings that are interrupted or
      that follow an interrupted milking. Under these restrictions (correct matching,
      interval of at least 4 h, and no interrupted milking), one sampled milking
      suffices to get a satisfactory estimate for the test-day fat yield.

PMID- 11949874
TI  - Relationships of productive life evaluations with changes in evaluations for
      yields.
AB  - The objective of this work was to investigate the relationships of productive
      life with changes in bull evaluations for yield traits. Two datasets were
      analyzed. In the first, predicted differences for change in milk yield from first
      to second lactation of daughters of artificial insemination (AI) Holstein bulls
      used widely in the southeastern United States were available from a previous
      study. These were correlated with predicted transmitting abilities (PTA) of
      productive life from May 2000 USDA sire evaluations. Based on bulls with at least
      10 daughters (n = 560) the correlation of PTA productive life with predicted
      differences for the change in milk yield was 0.30. The correlation increased to
      0.36 for bulls with at least 50 daughters (n = 319) and to 0.40 for bulls with at
      least 75 daughters (n = 284). The second analysis included data on 1831 AI
      sampled Holstein bulls evaluated by USDA between July 1989 and May 2000. Changes
      in PTA yields were calculated as PTA from evaluations based on first and second
      records of daughters minus those from first-record evaluations. Correlation
      analyses showed that PTA yields from first-record evaluation and changes in PTA
      yields were positively associated with productive life. Regression coefficients
      on changes in PTA yields were all positive indicating that increases in PTA for
      yield traits as daughters aged corresponded with longer productive life. Using
      changes in AI bull evaluations for yields could improve prediction of productive
      life for little cost.

PMID- 11949876
TI  - Calving interval and survival breeding values as measure of cow fertility in a
      pasture-based production system with seasonal calving.
AB  - In a grass-based production system with seasonal calving, fertility is of major
      economic importance. A delay in conception due to poor fertility prolongs
      intercalving interval and causes a shift in calving pattern, which can lead to
      culling. Calving interval (CIV) information is readily available from milk
      records; analyzing it, however, presents a problem, as it is only available for
      cows that conceive and calve again. Calving interval should therefore be treated
      as a censored trait. In this study, survival to the next lactation (SUV) was
      analyzed jointly with CIV in a multivariate linear model to account for the
      selection in CIV data. Genetic parameters for first lactation calving interval
      were estimated with a sire model for Holstein Friesian cows in Ireland. SUV was
      preadjusted for production within herd-year-season (HYS), while milk yield was
      included as a third trait in the analysis to account for the large effect it has
      on both traits. The residual covariance between CIV and SUV was fixed as 3 times
      the sire covariance within the model, as it was inestimable because of the
      structure of the data. Breeding values were estimated with various models to test
      the effect of culling and milk yield. Heritability was 0.04 +/- 0.006 for CIV and
      0.01 +/- 0.003 for SUV, while the genetic correlation between them was -0.28 (+/
      0.11). The genetic standard deviation was around 4% for SUV and 7 d for CIV. Sire
      predicted transmitting abilities for progeny tested bulls ranged between -5 and
      3% for survival rate and between -4 and 8 d for calving interval. Differences
      between the best and worst bull varied with model. Including SUV and milk yield
      as traits in the model reduced the mean and variance of sire predicted
      transmitting abilities but increased the coefficient of variation by 30% compared
      with the univariate model. The current model is expected to account for most of
      the genetic variation in fertility that is possible from calving dates and future
      extensions, such as the use of linear type trait or additional lactations for
      predicting survival, appear straightforward. These traits now form part of the
      national index for selecting dairy bulls in Ireland.

PMID- 11949877
TI  - Cerebrovascular inflammation following subarachnoid hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage frequently results in complications including
      intracranial hypertension, rebleeding and vasospasm. The extravasated blood is
      responsible for a cascade of reactions involving release of various vasoactive
      and pro-inflammatory factors (several of which are purported to induce vasospasm)
      from blood and vascular components in the subarachnoid space. The authors review
      the available evidence linking these factors to the development of inflammatory
      lesions of the cerebral vasculature, emphasizing: 1) neurogenic inflammation due
      to massive release of sensory nerve neuropeptides; 2) hemoglobin from lysed
      erythrocytes, which creates functional lesions of endothelial and smooth muscle
      cells; 3) activity, expression and metabolites of lipoxygenases cyclooxygenases
      and nitric oxide synthases; 4) the possible role of endothelin-1 as a pro
      inflammatory agent; 5) serotonin, histamine and bradykinin which are especially
      involved in blood-brain barrier disruption; 6) the prothrombotic and pro
      inflammatory action of complement and thrombin towards endothelium; 7) the
      multiple actions of activated platelets, including platelet-derived growth factor
      production; 8) the presence of perivascular and intramural macrophages and
      granulocytes and their interaction with adhesion molecules; 9) the evolution,
      origins, and effects of pro-inflammatory cytokines, especially IL-1, TNF-alpha
      and IL-6. Human and animal studies on the use of anti-inflammatory agents in
      subarachnoid hemorrhage include superoxide and other radical scavengers, lipid
      peroxidation inhibitors, iron chelators, NSAIDs, glucocorticoids, and serine
      protease inhibitors. Many animal studies claim reduced vasospasm, but these
      effects are not always confirmed in human trials, where symptomatic vasospasm and
      outcome are the major endpoints. Despite recent work on penetrating vessel
      constriction, there is a paucity of studies on inflammatory markers in the
      microcirculation.

PMID- 11949878
TI  - Pharmacokinetics of paeoniflorin after oral administration of Shao-yao Gan-chao
      Tang in mice.
AB  - Paeoniflorin, a monoterpene glycoside, is the principal bioactive component of
      Paeoniae Radix. The traditional prescription Shao-yao Gan-chao Tang (SGT; Kampo:
      Shakuyaku-Kanzo-To), which is composed of Paeoniae Radix and Glycyrrhizae Radix,
      has been widely used in China and Japan. Quantification of paeoniflorin in mouse
      plasma after oral administration of SGT (at a dose containing 10 mg/kg
      paeoniflorin) was achieved using a simple and rapid high-performance liquid
      chromatography method. The plasma concentration-time curves were fitted with mean
      terminal half-lives (t 1/2) of 116.17 min. The maximum plasma concentration
      (Cmax) of paeoniflorin was 111.56 ng/ml, time to reach maximum concentration
      (tmax) was 17.00 min, the area under the plasma concentration-time curve (AUC)0-t
      was 12293.42 ng x min/ml, clearance/bioavailability (CL/F) value was 644.74
      ml/min x kg, apparent volume of distribution/ bioavailability (Vd/F) value was
      103.05 l/kg, and the mean residence time (MRT) was 169.64 min. These results,
      together with the previously reported kinetic data of paeoniflorin after oral
      administration of Paeoniae Radix extract alone, indicated that absorption of
      paeoniflorin after oral administration of SGT was significantly greater than that
      after oral administration of Paeoniae Radix alone.

PMID- 11949879
TI  - Role of Rho-associated protein kinase and histamine in lysophosphatidic acid
      induced airway hyperresponsiveness in guinea pigs.
AB  - Inhalation of oleoyl lysophosphatidic acid (LPA) induced airway
      hyperresponsiveness to acetylcholine (ACh). In contrast, palmitoyl and stearoyl
      LPA exerted minimal effects. Airway hyperresponsiveness was inhibited by
      inhalation of Y-27632, an inhibitor of Rho-associated protein kinase (ROCK).
      Mepyramine, an H1 histamine receptor antagonist and ketotifen, an inhibitor of
      histamine release and H1 histamine receptor antagonist, also inhibited airway
      hyperresponsiveness induced by LPA; however, aspirin failed to attenuate this
      response. The incubation of lung fragments with LPA gave rise to releases in
      histamine. On the other hand, LPA produced no significant changes on the smooth
      muscle contraction evoked by ACh. These findings suggest that LPA-induced airway
      hyperresponsiveness is attributable to activation of the Rho/ROCK-mediated
      pathway via endothelial cell differentiation gene (EDG) receptors, probably EDG
      7. Moreover, histamine release may be involved.

PMID- 11949880
TI  - Necessity of enzymatic activity of alkaline phosphatase for mineralization of
      osteoblastic cells.
AB  - Alkaline phosphatase (ALP) is supposed to be important for bone formation;
      however, its role is not clear. In this study, we examined the importance of
      enzymatic activity of ALP and anchoring of ALP protein to the cells for
      mineralization of an osteoblastic cell line, MC3T3-E1. While we cultured the
      cells in the presence of tetramisole, an inhibitor of ALP activity, ALP protein
      was expressed at a similar level to that in the control. Although tetramisole
      showed no effect on cell growth and increased hydroxyproline accumulation, it
      decreased the osteocalcin production and the accumulation of calcium and
      phosphate in the matrices. Tetramisole also inhibited mineralized nodule
      formation, which was observed by optical microscopy and detected by Von Kossa
      staining. On the other hand, when ALP protein was released from the cell
      membranes with the use of phosphatidylinositol-specific phospholipase C, no
      marked changes were detected in hydroxyproline, calcium and phosphate
      accumulations in the matrices at late calcification stage, which was consistent
      with the morphological findings. These results clearly show that enzymatic
      activity of ALP is necessary for mineralization of MC3T3-E1 cells, but not the
      presence of ALP protein or anchoring of ALP to the cells.

PMID- 11949881
TI  - Effects of various reactive oxygen species on the guinea pig trachea and its
      epithelium.
AB  - Reactive oxygen species (ROS) are key factors playing important roles in tissue
      damage of airways under different pathological conditions. Effects of ROS
      (superoxide anion, H2O2 and hydroxyl radical) were recorded on isometric tension
      of intact and epithelium denuded, not precontracted guinea pig trachea.
      Superoxide anion was produced by xanthine/xanthine oxidase and hydroxyl radical
      either by FeSO4/H2O2 or FeSO4/ascorbic acid. In intact preparations, the muscle
      tension was unaffected by superoxide anion, while H2O2 and hydroxyl radical
      produced a biphasic response, contraction followed by relaxation. Both the
      amplitude and duration of contractions evoked by H2O2 were larger than those
      caused by hydroxyl radical producing systems. On denuded tracheal strips,
      superoxide anion elicited also a biphasic response, and the H2O2 and hydroxyl
      radical produced contractions were of higher amplitude and of longer duration
      than in intact tissues. Indomethacin pretreatment enhanced or slightly reduced
      the amplitude of contractions evoked by both H2O2 and hydroxyl radical on the
      intact and denuded preparations, respectively. Moreover, the duration of
      contractions of the trachea induced by oxidative systems was prolonged.
      Indomethacin did not affect the action of superoxide anion on the intact tissues
      and reduced the amplitude of the biphasic response on denuded ones.
      Nordihydroguaiaretic acid pretreatment did not alter the responses elicited by
      ROS in intact preparations and reduced their action on the denuded ones. Our
      results suggest that a) various ROS contract tracheal smooth muscle with
      simultaneous release of epithelium derived relaxing factors, b) epithelium
      possesses superoxide anion scavenging capacity which is high enough to protect
      smooth muscle from its actions, and c) cyclooxygenase products participate in
      relaxation and lipoxygenase products in contraction caused by ROS in the guinea
      pig trachea.

PMID- 11949882
TI  - A peroxisome proliferator-activated receptor gamma agonist influenced daily
      profile of energy expenditure in genetically obese diabetic rats.
AB  - Otsuka Long Evans Tokushima Fatty (OLETF) rats were developed as a model of non
      insulin-dependent diabetes mellitus (NIDDM) with mild obesity. We reported that
      the daily profiles of energy expenditure associated with two peaks (one between
      05:00 and 08:00 and the other between 20:00 and 22:00) were observed at 8 weeks
      of age (without NIDDM), while these two peaks disappeared at 24 weeks of age with
      NIDDM. As a new anti-diabetic drug, a peroxisome proliferator-activated receptor
      y agonist pioglitazone hydrochloride has been developed, we examined whether
      pioglitazone normalized daily profiles of energy expenditure at 24 weeks of age.
      A control diet and pioglitazone (0.1%)-containing diet were fed from 6 weeks of
      age. The two peaks of daily profiles of energy expenditure, which disappeared in
      OLETF rats with the control diet at 24 weeks of age, were reproduced by
      administration of pioglitazone. The respiratory quotient was lower and fat
      derived energy used for combustion was increased by pioglitazone at both ages.
      The body weight, daily food intake, plasma levels of fat, insulin, leptin and the
      wet weight of visceral fat were not influenced, but the levels of blood
      hemoglobin Alc and plasma tumor necrosis factor a were decreased by pioglitazone.
      Administration of pioglitazone improved daily profiles of energy expenditure via
      affecting glucose and fat metabolisms.

PMID- 11949883
TI  - Itch-associated response induced by experimental dry skin in mice.
AB  - The present study was conducted to establish a new mouse model of dry skin
      pruritus. The rostral back was treated daily with cutaneous application of
      acetone/ether (1:1) mixture (AE), water following AE (AEW), 1% sodium lauryl
      sulfate (SLS) or tape stripping (TS). On the day after 5-day treatment, although
      all four treatments significantly decreased stratum corneum (SC) hydration and
      increased transepidermal water loss (TEWL), only AEW treatment significantly
      increased spontaneous scratching. An increase in the frequency of TS produced the
      marked increase of TEWL, without significant effects on SC hydration and
      spontaneous scratching. In AEW-treated mice, changes in SC hydration and TEWL
      were marked in the initial 2-day period, while spontaneous scratching increased
      gradually from 3 days after starting the treatment. The degranulation of
      cutaneous mast cells was increased by SLS treatment but not by other treatments.
      There was no apparent difference in AEW-induced spontaneous scratching between
      mast cell-deficient mice (WBB6F1-W/Wv) and normal littermates (WBB6F1-+/+).
      Opioid antagonists, naloxone and naltrexone, (1 mg/kg, subcutaneously)
      significantly suppressed spontaneous scratching in AEW-treated mice. It is
      suggested that spontaneous scratching of AEW-treated mice is an itch-related
      response and a useful model for studying the mechanisms of dry skin pruritus.

PMID- 11949884
TI  - Effect of methamphetamine and imipramine on cerebral ischemia-induced
      hyperactivity in Mongolian gerbils.
AB  - Ischemia-induced hyperactivity is recognized several hours after both common
      carotid arteries' occlusion for 5 min in Mongolian gerbils, and it continues for
      at least 7 days. The aim of this study is to investigate the possible mechanisms
      of this abnormal behavior. Methamphetamine (MAP) (1 and 3 mg /kg) was
      administered for 7 days and imipramine (IMP) (5 and 10 mg/kg) was administered
      for 7 or 14 days. Bilateral carotid artery was occluded for 5 min 24 h after the
      last administrations of these drugs. MAP, which had been administered every day
      for 1 week, showed marked inhibition in the ischemia-induced hyperactivity.
      However, IMP did not have any effect even though it had been injected every day
      for 2 weeks. Hippocampal CA1 neuronal changes also appeared in the MAP- and IMP
      administered groups. As the dopaminergic neurotransmission is facilitated by the
      repeated administration of MAP, the ischemia-induced hyperactivity may be related
      to abnormalities in dopaminergic function. The participation of the other
      neurotransmitters is also discussed.

PMID- 11949885
TI  - Renal protective effect of candesartan cilexetil in spontaneously
      hypercholesterolemic rats.
AB  - Spontaneously hypercholesterolemic (SHC) rats exhibit hypercholesterolemia,
      proteinuria and focal glomerulosclerosis with age, and they finally die as a
      result of renal failure. In this study, the renoprotective effects of candesartan
      cilexetil, an angiotensin II type 1 receptor antagonist, and enalapril, an
      angiotensin I converting enzyme inhibitor, were examined in SHC rats. Candesartan
      cilexetil (0.1 and 1 mg /kg) and enalapril (10 mg/kg) were administered orally to
      10-week-old SHC rats for a 6-week period. Candesartan cilexetil (1 mg/kg) and
      enalapril (10 mg/kg) significantly inhibited proteinuria and hypercholesterolemia
      to a similar extent. In untreated 16-week-old SHC rats, glomerulosclerosis,
      basophilic change, cast formation and interstitial mononuclear cell infiltration
      were observed. Candesartan cilexetil (1 mg/kg) inhibited all of these
      histological changes. Enalapril inhibited glomerulosclerosis and cast formation.
      These results show that candesartan cilexetil and enalapril have renal protective
      effects in SHC rats. Thus, angiotensin II might play an important role in renal
      pathogenesis in a model of focal glomerulosclerosis with hypercholesterolemia.

PMID- 11949886
TI  - Cardiac effects of clinically available Kampo medicine assessed with canine
      isolated, blood-perfused heart preparations.
AB  - Cardiac effects of 10 kinds of clinically available Kampo medicines were
      investigated: Kakkon-to (TJ-1), Dai-saiko-to (TJ-8), Boi-ogi-to (TJ-20), Chorei
      to (TJ-40), Rokumi-gan (TJ-87), Tsu-do-san (TJ-105), Gosha-jinki-gan (TJ-107),
      San'o-shashin-to (TJ-113), Sairei-to (TJ-114) and Inchin-gorei-san (TJ-117).
      Chronotropic and inotropic effects were studied using canine isolated, blood
      perfused heart preparations, while subcellular mechanisms were analyzed by
      measuring the drug-induced changes of the adenylate cyclase activity in the
      canine ventricular membrane preparation. Intracoronary injections of TJ-1, TJ-20,
      TJ-105 and TJ-113 increased the sinoatrial rate and developed tension of
      papillary muscle in a dose-related manner, which was significantly attenuated by
      the pretreatment of the preparations with beta-blocker propranolol. Meanwhile,
      the other extracts hardly affected these parameters. TJ-1, TJ-20 and TJ-113
      increased the adenylate cyclase activity in a dose-related manner, but their
      potency was significantly less compared with that by an equivalent concentration
      of isoproterenol. Moreover, TJ-105 did not increase the adenylate cyclase
      activity. These results suggest that the positive chronotropic and inotropic
      effects of TJ-1, TJ-20, TJ- 105 and TJ-113 may be exerted through the direct
      stimulation of the beta-adrenoceptor and/or the norepinephrine release from the
      postganglionic nerve terminals in the heart.

PMID- 11949887
TI  - Enhanced cAMP response of naturally occurring mutant of human beta3-adrenergic
      receptor.
AB  - We have examined the functional significance of the naturally occurring mutation
      at position 64 of human beta3-adrenergic receptor (beta3AR), which changes the
      amino acid from tryptophan to arginine (W64R-beta3AR). The affinities of betaAR
      agonists for W64R-beta3AR expressed in COS-7 cells were not significantly
      different from those for wild type beta3AR. When two receptors are expressed at
      various expression levels, and stimulated with CGP12177A, they showed essentially
      the same EC50 values and maximal responses. Overexpression of Gi and Go, or the
      treatment with pertussis toxin did not affect the agonist-induced cAMP response,
      suggesting that Gi and Go did not contribute to the beta3AR-induced cAMP
      response. However, the enhanced cAMP response was observed when W64R-beta3AR was
      coexpressed with the adenylyl cyclase type III isoform, and stimulated by
      CGP12177A and isoproterenol. These results indicate that the cAMP response of
      W64R-beta3AR can be enhanced under the particular condition that adenylyl cyclase
      type III was coexpressed.

PMID- 11949888
TI  - Methadone and heroin antinociception: predominant delta-opioid-receptor responses
      in methadone-tolerant mice.
AB  - Antinociceptive tail flick responses to heroin and 6-monoacetylmorphine mediated
      in the brain by mu-opioid receptor are switched by morphine pellet implantation
      to delta1- and delta2-opioid-receptors mediation, respectively. Present results
      showed that the mu-receptor response (inhibited by beta-funaltrexamine) to
      methadone was changed by morphine pellet implantation to delta1 (inhibited by 7
      benzylidenenaltrexone)- and delta2 (inhibited by naltriben)-opioid-receptor
      responses. Methadone pellet implantation likewise changed mediation from mu- to
      delta-opioid receptors for heroin and methadone but not for morphine (beta
      funaltrexamine continued to inhibit). Methadone mu action in the brain was linked
      through a descending system to activate spinal serotonin receptors (inhibited by
      methysergide), but this link was gone in the methadone-pellet-implanted group. In
      the latter group, the new delta1- and delta2-receptor responses were mediated by
      spinal GABAA (inhibited by bicuculline) and GABAB (inhibited by 2
      hydroxysaclofen) receptors. These shifts in neuronal systems meant that mu
      receptors on a given neuron were not changed into delta receptors. Preliminary
      results showed that delta-agonist action for methadone was prevented from
      appearing by MK801, a NMDA-receptor antagonist, and did not occur in 129S6/SvEv
      mice which lack NMDA responsiveness. Could methadone maintenance treatment in
      humans uncover delta-agonist actions?

PMID- 11949889
TI  - Use of anti-platelet-endothelial cell adhesion molecule-1 antibody in the control
      of disease progression in established collagen-induced arthritis in DBA/1J mice.
AB  - Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is expressed on the
      membrane of leukocytes and vascular endothelial cells. PECAM-1 has been shown to
      play an important role in the process of leukocyte transmigration in various
      animal models of acute inflammation. We investigated the role of PECAM-1 in the
      progression of arthritis by systemically administering anti-murine PECAM-1
      monoclonal antibody, 2H8, to DBA/1J mice with collagen-induced arthritis (CIA).
      Subcutaneous administration of dexamethasone (0.5 mg/kg per 2 days) significantly
      reduced hindpaw swelling and the clinical score of established CIA.
      Intraperitoneal administration of 2H8 (0.25 mg/mouse per 2 days) significantly
      inhibited hindpaw swelling in a time-dependent manner. 2H8 also significantly
      prevented further deterioration in the clinical score, but failed to reverse
      joint destruction discernible at the histological level. Both dexamethasone and
      2H8 inhibited body weight decrease by preventing the further development of
      arthritis. Histopathological assessment revealed that 2H8, as well as
      dexamethasone, inhibited inflammatory cell transmigration into the synovium of
      the hind paw joint and ameliorated synovitis and cartilage erosion. These results
      suggest that PECAM-1 plays an important role in the progression of CIA and that
      an inhibitor of PECAM-1 might have therapeutic value for clinical treatment of
      rheumatoid arthritis.

PMID- 11949890
TI  - Electrophysiological, anatomical and histological remodeling of the heart to AV
      block enhances susceptibility to arrhythmogenic effects of QT-prolonging drugs.
AB  - The present study was designed to investigate what kinds of adaptation occurred
      in the canine chronic AV block model, which has been used to study torsade de
      pointes (TdP). Dogs at 7-10 days (acute phase) and 28-56 days (chronic phase)
      after AV block were assessed. Ventricular effective refractory period and
      monophasic action potential duration were prolonged in chronic animals compared
      with acute animals; moreover the electrically vulnerable period was prolonged in
      chronic animals. Non-specific IKr channel blocker cisapride (1 and 10 mg/kg,
      p.o.) was administered without anesthesia to estimate the feasibility of QT
      prolongation. In chronic animals, QT prolongation followed by TdP was induced in
      one dog by the low dose and in all by the high dose, which was not observed in
      acute animals. MR images indicated increases of diameter and wall thickness of
      both ventricles in chronic animals. The degree of hypertrophy was prominent in
      the right ventricular wall and septal wall. Heart weight of the chronic animals
      was 1.7 times greater than that of normal control subjects. Photo- and electron
      micrograph analyses showed myocardial cell hypertrophy with parallel increases of
      collagen fiber and extracellular space in chronic animals. These
      electrophysiological, anatomical and histological adaptations may predispose the
      chronic AV block heart to drug-induced QT prolongation with enhanced risk of re
      entry and early after depolarization, leading to the onset of TdP.

PMID- 11949891
TI  - Intradermal cholinergic agonists induce itch-associated response via M3
      muscarinic acetylcholine receptors in mice.
AB  - In the present study, we examined whether cholinergic agonists would elicit an
      itch-associated response in mice. When mice were given an intradermal injection
      of carbachol (1-10 nmol) or bethanechol (0.3-100 nmol) into the rostral back,
      they showed the dose-dependent increase of scratching. Nicotine (1-10 nmol)
      showed no effect. Pretreatment with naloxone, but not with terfenadine,
      significantly suppressed the carbachol-induced scratching. When intradermally co
      injected with carbachol, atropine and 4-DAMP but neither methoctramine nor
      pancuronium significantly inhibited the carbachol-induced scratching. Muscarinic
      agonists are suggested to produce itch through activation of M3 muscarinic
      receptors in the skin.

PMID- 11949892
TI  - Effects of Puerariae radix on cell proliferation and nitric oxide synthase
      expression in dentate gyrus of alcohol-intoxicated Sprague-Dawley rats.
AB  - Traditionally, Puerariae radix had been used for the treatment of alcohol-related
      problems. In this study, effects of Puerariae radix on cell proliferation and
      nitric oxide synthase expression in the dentate gyrus of alcohol-intoxicated
      Sprague-Dawley rats were investigated via 5-bromo-2'-deoxyuridine (BrdU)
      immunohistochemistry and nicotinamide adenine dinucleotide phosphate-diaphorase
      (NADPH-d) histochemistry. Alcohol administration was shown to inhibit the numbers
      of both BrdU-positive and NADPH-d-positive cells, while Puerariae radix treatment
      was shown to increase those numbers. It is possible that nitric oxide, which
      might play an important role in the regulation of cell proliferation, is a major
      target of the toxic effects of alcohol.

PMID- 11949893
TI  - Cardiac effects of a selective rho-associated kinase inhibitor, Y-27632, assessed
      in canine isolated, blood-perfused heart preparations.
AB  - Chronotropic, inotropic and coronary effects of Y-27632 ((+)-(R)-trans-4-(1
      aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate), a
      specific inhibitor of Rho-associated coiled-coil forming protein serine/threonine
      kinase (ROCK), were assessed using canine isolated, blood-perfused heart
      preparations. Y-27632 slightly enhanced sinoatrial automaticity and significantly
      increased coronary blood flow, while it decreased ventricular contraction. The
      concentrations of Y-27632 needed to cause the currently observed changes were
      similar to those inhibiting ROCK in a previous in vitro study. These results
      suggest that the constitutional ROCK in the heart mainly regulates the
      ventricular contractility and coronary vascular tone rather than the sinoatrial
      automaticity.

PMID- 11949894
TI  - Molecular mechanisms of cardiostimulatory effects of sildenafil.
AB  - To better understand the molecular mechanisms of the previously described
      cardiostimulatory action of the phosphodiesterase type-5 (PDE5) inhibitor
      sildenafil, we first evaluated its effects on cyclic AMP level in the canine
      ventricular membrane preparation. Sildenafil (10 micromol/L) significantly
      increased the net cyclic AMP production rate, the potency of which was similar to
      that of 3-isobutyl-1-methylxanthine (IBMX). Next, we assessed the inhibitory
      effect of sildenafil on PDE of bovine heart. Sildenafil (> or = 1 micromol/L) as
      well as IBMX significantly decreased the cyclic AMP hydrolyzing speed of PDE.
      These results suggest that a supra-therapeutic concentration of sildenafil may
      directly inhibit cyclic AMP hydrolyzing PDEs in the heart, although indirect
      inhibition of PDE3 via the "cross-talk" pathway cannot be totally excluded.

PMID- 11949895
TI  - The perception of static subjective contours in infancy.
AB  - Only a few empirical investigations have focused on infants' ability to perceive
      static subjective contours. Furthermore, these experiments have provided
      contradictory findings regarding the age at which this capability emerges. The
      present study examined the development of infants' sensitivity to an elliptical
      version of the subjective circle described by Ehrenstein. A habituation
      dishabituation procedure was used to test the ability of 4-, 5-, and 7-month-old
      infants (N = 128) to differentiate between a subjective ellipse and a
      nonsubjective pattern that was constructed by displacing the inducing elements of
      the illusory figure. Results indicated that even the 4-month-olds were capable of
      discriminating between the subjective ellipse and the nonillusory display. A
      control experiment secured that this behavior was not generated by certain local
      differences between the test patterns. Furthermore, the results suggest that the
      perceived strength of the subjective contour was size dependent. This observation
      is discussed within the context of more recent neurophysiological models.

PMID- 11949896
TI  - Neurocognitive function and joint attention ability in young children with autism
      spectrum disorder versus developmental delay.
AB  - Studies have shown that young children with autism are not impaired on prefrontal
      tasks relative to what would be expected for their mental age, raising questions
      about the executive dysfunction hypothesis of autism. These studies did not
      include ventromedial prefrontal tasks, however. The present study examined
      whether young children with autism spectrum disorder (ASD) are impaired on
      ventromedial prefrontal tasks, and whether performance on such tasks is
      correlated with a core autism symptom, joint attention ability. Seventy-two 3- to
      4-year-old children with ASD, 34 3- to 4-year-old developmentally delayed
      children, and 39 12- to 46-month-old typically developing children, matched on
      mental age, were administered ventromedial and dorsolateral prefrontal tasks and
      joint attention tasks. Children with ASD performed similarly to comparison groups
      on all executive function tasks, indicating that at this early age, there is no
      autism-specific pattern of executive dysfunction. Ventromedial, but not
      dorsolateral, prefrontal task performance was strongly correlated with joint
      attention ability, however. The ventromedial prefrontal cortex is hypothesized to
      play a role in the development of joint attention and possibly some aspects of
      the autistic syndrome.

PMID- 11949897
TI  - Emergence of graphic symbol functioning and the question of domain specificity: a
      longitudinal training study.
AB  - The impact of social scaffolding on the emergence of graphic symbol functioning
      was explored in a longitudinal training study. Links among graphic, language, and
      play domains in symbolic development were also investigated. The symbolic
      functioning of 16 children, who were 28 months at the outset of the study, was
      assessed in comprehension and production tasks across the three domains at
      monthly intervals from 28 to 36 months, and again at 42 months. Training was
      delivered in between monthly assessments during weekly visits. Half of the
      children received training, which consisted of the experimenter drawing common
      objects and highlighting the relation between pictures and their referents, for
      16 consecutive weeks early in the study (early training, ET). The remaining half
      received a placebo version of training for these 16 weeks, followed by actual
      training for 4 weeks in the fifth month (late training, LT). After the first 4
      months of training the ET group was found to have accelerated comprehension and
      production of graphic symbols relative to the LT group. After the fifth month,
      the LT group reached the same level of graphic symbol performance as the ET
      group. There were strong positive correlations found among graphic symbol
      functioning and language and play, and between play and language. These findings
      support the view that graphic symbolic development can be influenced by cultural
      scaffolding, that more extensive training is needed early rather than later in
      development, and that interrelationships exist among symbolic domains.

PMID- 11949898
TI  - Generalizing the dynamic field theory of the A-not-B error beyond infancy: three
      year-olds' delay- and experience-dependent location memory biases.
AB  - Thelen and colleagues recently proposed a dynamic field theory (DFT) to capture
      the general processes that give rise to infants' performance in the Piagetian A
      not-B task. According to this theory, the same general processes should operate
      in noncanonical A-not-B-type tasks with children older than 12 months. Three
      predictions of the DFT were tested by examining 3-year-olds' location memory
      errors in a task with a homogeneous task space. Children pointed to remembered
      locations after delays of 0 s to 10 s. The spatial layout of the possible targets
      and the frequency with which children moved to each target was varied. As
      predicted by the DFT, children's responses showed a continuous spatial drift
      during delays toward a longer term memory of previously moved-to locations.
      Furthermore, these delay-dependent effects were reduced when children moved to an
      "A" location on successive trials, and were magnified on the first trial to a
      nearby "B" location. Thus, the DFT generalized to capture the performance of 3
      year-old children in a new task. In contrast to predictions of the DFT, however,
      3-year-olds' responses were also biased toward the midline of the task space-an
      effect predicted by the category adjustment (CA) model. These data suggest that
      young children's spatial memory responses are affected by delay- and experience
      dependent processes as well as the geometric structure of the task space.
      Consequently, two current models of spatial memory-the DFT and the CA model
      provide incomplete accounts of children's location memory abilities.

PMID- 11949899
TI  - Sleep, neurobehavioral functioning, and behavior problems in school-age children.
AB  - The aim of this study was to examine the associations between sleep and
      neurobehavioral functioning (NBF) in school-age children. These variables were
      assessed for 135 unreferred, healthy school children (69 boys and 66 girls), from
      second-, fourth-, and sixth-grade classes. Objective assessment methods were used
      on the participants in their regular home settings. Sleep was monitored using
      actigraphy for 5 consecutive nights; and NBF was assessed using a computerized
      neurobehavioral evaluation system, administered twice, at different times of the
      day. Significant correlations between sleep-quality measures and NBF measures
      were found, particularly in the younger age group. Children with fragmented sleep
      were characterized by lower performance on NBF measures, particularly those
      associated with more complex tasks such as a continuous performance test and a
      symbol-digit substitution test. These children also had higher rates of behavior
      problems as reported by their parents on the Child Behavior Checklist. These
      results highlight the association between sleep quality, NBF, and behavior
      regulation in child development; and raise important questions about the origins
      of these associations and their developmental and clinical significance.

PMID- 11949900
TI  - How children use input to acquire a lexicon.
AB  - The contributions of social processes and computational processes to early
      lexical development were evaluated. A re-analysis and review of previous research
      cast doubt on the sufficiency of social approaches to word learning. An empirical
      investigation of the relation of social-pragmatic and data-providing features of
      input to the productive vocabulary of sixty-three 2-year-old children revealed
      benefits of data provided in mother-child conversation, but no effects of social
      aspects of those conversations. The findings further revealed that the properties
      of data that benefit lexical development in 2-year-olds are quantity, lexical
      richness, and syntactic complexity. The nature of the computational mechanisms
      implied by these findings is discussed. An integrated account of the roles of
      social and computational processes to lexical development is proposed.

PMID- 11949901
TI  - Preschoolers are sensitive to the speaker's knowledge when learning proper names.
AB  - Unobservable properties that are specific to individuals, such as their proper
      names, can only be known by people who are familiar with those individuals. Do
      young children utilize this "familiarity principle" when learning language?
      Experiment 1 tested whether forty-eight 2- to 4-year-old children were able to
      determine the referent of a proper name such as "Jessie" based on the knowledge
      that the speaker was familiar with one individual but unfamiliar with the other.
      Even 2-year-olds successfully identified Jessie as the individual with whom the
      speaker was familiar. Experiment 2 examined whether children appreciate this
      principle at a general level, as do adults, or whether this knowledge may be
      specific to certain word-learning situations. To test this, forty-eight 3- to 5
      year-old children were given the converse of the task in Experiment 1--they were
      asked to determine the individual with whom the speaker was familiar based on the
      speaker's knowledge of an individual's proper name. Only 5-year-olds reliably
      succeeded at this task, suggesting that a general understanding of the
      familiarity principle is a relatively late developmental accomplishment.

PMID- 11949902
TI  - Parental involvement in the development of children's reading skill: a five-year
      longitudinal study.
AB  - This article presents the findings of the final phase of a 5-year longitudinal
      study with 168 middle- and upper middle-class children in which the complex
      relations among early home literacy experiences, subsequent receptive language
      and emergent literacy skills, and reading achievement were examined. Results
      showed that children's exposure to books was related to the development of
      vocabulary and listening comprehension skills, and that these language skills
      were directly related to children's reading in grade 3. In contrast, parent
      involvement in teaching children about reading and writing words was related to
      the development of early literacy skills. Early literacy skills directly
      predicted word reading at the end of grade 1 and indirectly predicted reading in
      grade 3. Word reading at the end of grade 1 predicted reading comprehension in
      grade 3. Thus, the various pathways that lead to fluent reading have their roots
      in different aspects of children's early experiences.

PMID- 11949903
TI  - Guilt in young children: development, determinants, and relations with a broader
      system of standards.
AB  - In this comprehensive study of the early development of guilt, 106 children were
      observed in laboratory paradigms in which they were led to believe that they had
      damaged valuable objects, during two separate sessions at each of the assessments
      at 22, 33, and 45 months. The behavioral and affective components of guilt
      cohered significantly across the sessions, converged with each other, were stable
      across all the assessments, and corresponded modestly with maternal reports. Most
      components decreased with age, except for bodily tension, which increased. At 33
      and 45 months, girls displayed more guilt than did boys. Children who were more
      fearful in typical fear-inducing paradigms also displayed more guilt. Children of
      mothers who relied on more power-assertive discipline, observed and self
      reported, displayed less guilt. Guilt related positively to the development of
      self at 18 months and to moral self at 56 months. Children who displayed more
      guilt were less likely to violate rules of conduct at 56 months. A mediational
      model was supported: Fearful temperament contributed to guilt proneness, which in
      turn served to inhibit children's tendency to violate rules.

PMID- 11949904
TI  - Stability and social-behavioral consequences of toddlers' inhibited temperament
      and parenting behaviors.
AB  - A prospective longitudinal design was employed to ascertain whether different
      types of behavioral inhibition (i.e., traditional, peer-social) were stable from
      toddler to preschool age, and whether inhibited temperament and/or parenting
      style would predict children's subsequent social and behavioral problems. At Time
      1, 108 toddlers (54 males, 54 females) and their mothers were observed in the
      Traditional Inhibition Paradigm and in a toddler-peer session; then at age 4
      years, 88 children were observed with unfamiliar peers, and maternal ratings of
      psychological functioning were obtained. How mothers and their toddlers
      interacted was also observed. Results revealed meaningful connections between
      toddler inhibition, maternal intrusive control and derision, and nonsocial
      behaviors at age 4. Both forms of toddler inhibition predicted socially reticent
      behavior during free play at 4 years. If mothers demonstrated relatively high
      frequencies of intrusive control and/or derisive comments, then the association
      between their toddlers' peer inhibition and 4-year social reticence was
      significant and positive; whereas if mothers were neither intrusive nor derisive,
      then toddlers' peer inhibition and 4-year reticence were not significantly
      associated. Thus, maternal behaviors moderated the relation between toddlers'
      peer inhibition and preschoolers' social reticence.

PMID- 11949905
TI  - Obstetrical complications and violent delinquency: testing two developmental
      pathways.
AB  - This study focused on the interaction between specific obstetrical complications
      and early family adversity in predicting violent behavior during childhood and
      adolescence, in a sample of 849 boys from low socioeconomic areas of Montreal,
      Canada. Obstetrical complication data from medical records were used to create
      three scales using a nonlinear principal component analysis followed by rotation.
      Family adversity and teacher-rated physical aggression were assessed when the
      boys were in kindergarten and self-reports of delinquency were collected when
      they were 17. Elevated scores on the Deadly Risk Situation scale of obstetrical
      complications (preeclampsia, umbilical cord prolapse, and induced labor)
      increased the risk of being violent at both 6 and 17 years of age, only among
      boys who grew up in high adverse familial environments. Moreover, this
      interaction partly accounted for the continuity between violence in childhood and
      adolescence. Interventions for young pregnant women from deprived environments
      and their babies are discussed in light of these results.

PMID- 11949906
TI  - Changes in children's self-competence and values: gender and domain differences
      across grades one through twelve.
AB  - This study extended previous research on changes in children's self-beliefs by
      documenting domain-specific growth trajectories for 761 children across grades 1
      through 12 in a longitudinal study of perceptions of self-competence and task
      values. Hierarchical Linear Modeling was used to (1) describe changes in beliefs
      across childhood and adolescence within the domains of mathematics, language
      arts, and sports; (2) examine the impact of changes in competence beliefs on
      changes in values over time in the same domains; and (3) describe gender
      differences in mean levels and trajectories of change in competence beliefs and
      values. The most striking finding across all domains was that self-perceptions of
      competence and subjective task values declined as children got older, although
      the extent and rate of decline varied across domains. For example, in language
      arts, competence beliefs declined rapidly during the elementary school years, but
      then leveled off or increased to some extent; whereas the decline in self
      competence beliefs in sports accelerated during the high school years.
      Significant gender differences in beliefs were found in most domains; however,
      the gender differences in developmental trajectories appeared to be domain
      specific rather than global. Importantly, the gender differences between boys and
      girls did not systematically increase with age, as predicted by some
      socialization perspectives. Adding competence beliefs as an explanatory variable
      to the model for task values revealed that changes in competence beliefs
      accounted for much of the age-related decline in task values. In addition,
      competence beliefs accounted for most of the gender differences in task values
      for language arts and sports.

PMID- 11949907
TI  - Predictability of observed mother-child interaction from preschool to middle
      childhood in a high-risk sample.
AB  - This study examined predictability of observed parent-child interaction from
      preschool to middle childhood in 283 mother-child dyads. Participants were
      welfare recipients enrolled in the Observational Study of the Job Opportunities
      and Basic Skills Training Program. Structured observational sessions were
      conducted both at preschool age and middle childhood, and were coded for maternal
      social behavior, child social behavior, and dyadic interaction. Analyses explored
      direct relations between the assessments; relations between the assessments with
      possible third-variable influences, such as maternal literacy, covaried out; and
      moderated relations. Results indicated that observed mother-child interaction in
      middle childhood could be significantly predicted from observed interaction 4
      years earlier. Risk status moderated the relations such that those families with
      greater risk factors tended to show more stability, although this stability was,
      at times, through maintaining suboptimal functioning.

PMID- 11949908
TI  - Assessing children's emotional security in the interparental relationship: the
      Security in the Interparental Subsystem Scales.
AB  - Guided by the emotional security hypothesis, this study reports on the
      development of a new self-report measure that assesses children's strategies for
      preserving emotional security in the context of interparental conflict.
      Participants were 924 sixth, seventh, and eighth graders and a subset of their
      mothers, fathers, and teachers. Exploratory and confirmatory factor analyses of
      the Security in the Interparental Subsystem (SIS) Scale supported a seven-factor
      solution, corresponding well to the three component processes (i.e., emotional
      reactivity, regulation of exposure to parent affect, and internal
      representations) outlined in the emotional security hypothesis. The SIS subscales
      demonstrated satisfactory internal consistency and test-retest reliability.
      Support for the validity of the SIS Scale is evidenced by its significant links
      with parent reports of children's overt reactivity to conflict, children's
      responses to interparental conflict simulations 6 months later, and children's
      psychological maladjustment and experiential histories with interparental
      conflict across multiple informants (i.e., child, mother, father, and teacher).
      Results are discussed in the context of developing recommendations for use of the
      SIS and advancing the emotional security hypothesis.

PMID- 11949909
TI  - Domain-specific antecedents of parental psychological control and monitoring: the
      role of parenting beliefs and practices.
AB  - This research examined the effects of domain-differentiated beliefs about
      legitimate parental authority and ratings of restrictive parental control on
      adolescent- and mother-reported psychological and behavioral control. The
      influence of parenting beliefs and practices regarding socially regulated (moral
      and conventional) and ambiguously personal (multifaceted and personal) issues was
      examined in 93 middle-class African American early adolescents (M = 13.11 years,
      SD = 1.29) and their mothers, who were followed longitudinally for 2 years.
      Domain-specific parenting beliefs and ratings predicted adolescent-reported
      maternal psychological control and parental monitoring, but the nature and
      direction of the relations differed. Adolescents who rated parents as more
      restrictive in their control of personal issues and who believed that parents
      should have less legitimate authority over these issues rated their mothers as
      higher in psychological control. In contrast, more adolescent-reported parental
      monitoring was associated with gender (being female) and adolescents' beliefs
      that parents have more legitimate authority to regulate personal issues. As
      expected, adolescent age and gender influenced mother-reported monitoring and
      psychological control; in addition, the effects of mothers' ratings of
      restrictive control on both psychological control and monitoring were moderated
      by gender. The results indicate that psychological control and monitoring can be
      understood in terms of the particular behaviors that are controlled, as well as
      the style in which control is exercised.

PMID- 11949910
TI  - Emotion regulation in context: the jealousy complex between young siblings and
      its relations with child and family characteristics.
AB  - Jealousy is a social emotion that has received little attention by developmental
      researchers. The current study examined sibling jealousy and its relations to
      child and family characteristics in 60 families with a 16-month-old toddler and
      an older preschool-age sibling. Sibling jealousy was elicited in social triads
      consisting of a parent (mother or father) and the two siblings. Positive marital
      relationship quality (i.e., love and relationship maintenance) was a particularly
      strong predictor of the older siblings' abilities to regulate jealousy reactions
      in the mother sessions. Younger siblings' jealous affect with mothers was linked
      to the child's temperament, whereas older siblings' jealous affect with mothers
      was related to the child's emotional understanding. Younger siblings displayed
      more behavioral dysregulation in the mother-sibling triads if there was greater
      sibling rivalry reported by mothers. Session order (i.e., which sibling was
      challenged first in the jealousy paradigm) had a strong effect on both the affect
      and behavioral dysregulation displayed by the older and younger siblings. Results
      are discussed with respect to the need for future research to consider social
      relationships as developmental contexts for young children's emotion regulation.

PMID- 11949911
TI  - Children and welfare reform: a view from an experimental welfare program in
      Minnesota.
AB  - Little is known about the effects of the most recent welfare reform initiatives-
      which include work mandates, time limits, and enhanced earnings disregards--on
      children's outcomes. This is partly because the ways in which maternal employment
      and income affect children more generally are not well understood. This article
      describes the effects on child development of the Minnesota Family Investment
      Program (MFIP), a welfare program that began prior to 1996 federal welfare reform
      legislation. The present study utilized MFIP's unique, three-group research
      design to untangle the effects of different components of the program, and, in
      turn, discover how each component's effects on parents' income or employment
      affected children's development. This study's findings showed that MFIP increased
      employment rates and decreased poverty and, according to reports from mothers,
      children were less likely to exhibit problem behaviors and more likely to perform
      better and be more highly engaged in school. These findings, based on a total of
      879 participants, bolster the long-standing literature that has associated
      poverty with worse outcomes for children by confirming, in a rigorous experiment,
      that incremental increases in income for working poor parents bring benefits to
      children.

PMID- 11949912
TI  - Old friends, new friends: predictors of children's perspective on their friends
      at school.
AB  - Predictors of 5-year-old kindergartners' insights into their friends, and their
      accounts of liking and conflict with their friends were investigated, with a
      focus on both the children's and their friends' social understanding during the
      preschool period, and the quality of their preschool friendships. Seventy
      children initially studied at 4 years utilizing social cognition tasks and
      observations of dyadic play with their friends were followed over the transition
      to school; at school they were interviewed about their friendships and their
      social understanding was assessed. One group had remained close to their
      preschool friends, whereas a second group had formed new friendships. Social
      understanding, language abilities, and prosocial characteristics of both the
      children and preschool friends, their successful communication and shared pretend
      play experiences during the preschool period, and their mothers' educational
      level were related to their perspectives on their current school friends. Liking
      of current friends was linked to relationship history and maternal educational
      level for both those with old and with new friends, whereas insight was related
      to assessments of social cognition.

PMID- 11949913
TI  - Hostility, hostile detachment, and conflict engagement in marriages: effects on
      child and family functioning.
AB  - This study examined the relations between patterns of marital communication,
      child adjustment, and family functioning. Couples with a 4- or 5-year-old child
      were divided into three groups (N = 126) based on observed patterns of emotional
      communication: Hostile couples showed a cumulative increase in negative speaker
      behaviors over the course of a high-conflict marital discussion; hostile
      withdrawn couples showed a cumulative increase in both negative speaker and
      negative listener behaviors over the course of the interaction; and engaged
      couples showed a cumulative increase in both positive speaker and listener
      behaviors over the course of the interaction. The families of these three types
      of couples were then compared on child outcomes (i.e., peer relations, behavior
      problems), parenting quality, co-parenting quality, and family-level functioning.
      Differences in marital violence and marital satisfaction between marital couples
      were also examined in relation to family risk. Families in which couples were
      hostile-detached showed the most negative outcomes. Hostile-detached couples were
      more likely than hostile or conflict-engaging couples to use more power-assertive
      methods of discipline; to be ineffective in co-parenting their child; to have
      family units that were less cohesive, less playful, and more conflictual; and to
      have children that exhibited behavior problems. Results also indicated that
      marital typology still accounted for significant variance in child outcome after
      controlling for marital violence and marital satisfaction. Differences in the
      absolute degree of negative behaviors also did not account for results. Findings
      are discussed in terms of the detrimental impact of marital conflict on child and
      family functioning.

PMID- 11949914
TI  - Adoption losses: naturally occurring or socially constructed?
AB  - The American definition of kinship based on biological ties, the practice of
      closed adoption, and stigmas associated with adoption may decisively influence
      adoption-related losses. Cross-cultural and historical accounts of adoption that
      do not apply to these contemporary American constructs of parenthood and
      practices of adoption suggest outcomes that are not as integrally based on loss.
      Adoption in infancy is defined as parenting a child with one set of (adoptive)
      parents and two (adoptive and birth) families. Implications for adoption
      research, policy, and practice are discussed.

PMID- 11949915
TI  - Health care utilization and adults who are deaf: relationship with age at onset
      of deafness.
AB  - OBJECTIVES: To evaluate the health care utilization of a nationally
      representative sample of U.S. deaf adults while accounting for the age at onset
      of deafness, an indicator of linguistic and sociocultural group affiliation. DATA
      SOURCES/STUDY SETTING: Data from the 1990 to 1991 National Health Interview
      Surveys the most recent years the Hearing Supplement was administered. The data
      were collected during in-home interviews of a sample of the U.S. civilian
      noninstitutionalized population. STUDY DESIGN: Cross-sectional analyses comparing
      health-related measures of adults deafened before (prelingually) and after
      (postlingually) the age of 3 and those of a representative sample of the general
      population, adjusting for sociodemographics and health status. Key measures were
      physician visits and preventive health care services utilization. PRINCIPAL
      FINDINGS: Compared with the general population, prelingually deafened adults had
      fewer physician visits and were less likely to have visited a physician in the
      preceding 2 years, whereas postlingually deafened adults had more physician
      visits and were more likely to have visited a physician in the preceding 2 years.
      Postlingually deafened women were less likely to have had a mammogram within the
      previous 2 years. CONCLUSIONS: In terms of health care utilization, the deaf
      population is heterogeneous. Prelingually deafened adults' use of health care is
      similar to that of other language minority groups. Postlingually deafened adults'
      use of health care services appears similar to people with chronic illness.
      Future studies must distinguish different groups of people with hearing loss in
      order to identify barriers and monitor improvements in health care services
      access.

PMID- 11949916
TI  - Impact of the Oregon Health Plan on access and satisfaction of adults with low
      income.
AB  - OBJECTIVE: To evaluate the effects of the Oregon Health Plan (OHP) on beneficiary
      access and satisfaction. DATA SOURCES: Telephone survey of nondisabled adults in
      1998. STUDY DESIGN: Two groups of adults were surveyed: OHP enrollees and Food
      Stamp recipients not enrolled in OHP. The Food Stamp sample included both
      privately insured and uninsured recipients. This allowed us to disentangle the
      insurance effects of OHP from other effects such as its reliance on managed care
      and the priority list. OHP and Food Stamp adults were compared along the
      following measures: usual source of care, utilization of health care services,
      unmet need, and satisfaction with care. DATA COLLECTION: The survey was conducted
      by telephone, using computer-assisted telephone interviewing techniques.
      PRINCIPAL FINDINGS: Much of OHP's impact has been realized by its extension of
      health insurance coverage to Oregon's low-income residents. The availability of
      health insurance significantly increased the utilization of many health care
      services and reduced unmet need for care. OHP was associated within a higher
      percentage of enrollees having a usual source of care and higher rates of Pap
      test screening among women compared with Food Stamp recipients. OHP enrollees
      also reported significantly higher use of dental care and prescription drugs; use
      we attribute to the expanded benefit package under the priority list. At the same
      time, OHP enrollees reported a greater unmet need for prescription drugs. Drug
      treatment for below-the-line conditions was one reason for this unmet need, but
      often the specific drug simply was not in the plan's formulary. OHP enrollees
      were as satisfied with their health care as those Food Stamp recipients with
      private health insurance. CONCLUSIONS: Despite the negative publicity prior to
      its implementation, there is no evidence that "rationing" under OHP's priority
      list has substantially restricted access to needed services. OHP adults appear to
      enjoy access equal to or better than that of low-income persons with private
      health insurance and have far greater access than the uninsured.

PMID- 11949917
TI  - Physician, practice, and patient characteristics related to primary care
      physician physical and mental health: results from the Physician Worklife Study.
AB  - OBJECTIVE: To study the impact that physician, practice, and patient
      characteristics have on physician stress, satisfaction, mental, and physical
      health. DATA SOURCES: Based on a survey of over 5,000 physicians nationwide. Four
      waves of surveys resulted in 2,325 complete responses. Elimination of ineligibles
      yielded a 52 percent response rate; 1,411 responses from primary care physicians
      were used. STUDY DESIGN: A conceptual model was tested by structural equation
      modeling. Physician job satisfaction and stress mediated the relationship between
      physician, practice, and patient characteristics as independent variables and
      physician physical and mental health as dependent variables. PRINCIPLE FINDINGS:
      The conceptual model was generally supported. Practice and, to a lesser extent,
      physician characteristics influenced job satisfaction, whereas only practice
      characteristics influenced job stress. Patient characteristics exerted little
      influence. Job stress powerfully influenced job satisfaction and physical and
      mental health among physicians. CONCLUSIONS: These findings support the notion
      that workplace conditions are a major determinant of physician well-being. Poor
      practice conditions can result in poor outcomes, which can erode quality of care
      and prove costly to the physician and health care organization. Fortunately,
      these conditions are manageable. Organizational settings that are both "physician
      friendly" and "family friendly" seem to result in greater well-being. These
      findings are particularly important as physicians are more tightly integrated
      into the health care system that may be less clearly under their exclusive
      control.

PMID- 11949918
TI  - Helpful or harmful? The impact of strategic change on the performance of U.S.
      urban hospitals.
AB  - OBJECTIVE: To contribute to the debate as to whether strategic change helps or
      harms organizations by empirically examining how strategic change influences
      performance change in urban hospitals. DATA SOURCES: AHA Annual Survey (1994 and
      1996), Health Care Financing Administration's Medicare Cost Reports (1994 and
      1996) and Medicare HMO Files (1994), U.S. Bureau of the Census' County Business
      Patterns Files (1994), and Area Resources File (1994). STUDY DESIGN: This work
      employed a longitudinal approach using a panel design to study the effect of
      environmental and organizational characteristics on urban hospital strategic
      behavior and performance. A path analytic model was used to examine the
      simultaneous effects of environmental and organizational characteristics (1994)
      on strategic behavior (change in strategies to enhance HMO business and change in
      strategies to control costs 1994-96), as well as the effects of all of these
      variables on change in urban hospital performance (change in market share, change
      in operational efficiency, change in financial performance 1994-96). PRINCIPAL
      FINDINGS: (1) Environmental context exerts a greater influence on urban
      hospitals' HMO business enhancement strategies, whereas organizational
      characteristics have more influence on cost-control strategies. (2) Between the
      two strategies, HMO business enhancement and cost control, strategic change to
      enhance business with HMOs is much more complex. (3) Strategic change observed
      across the 1994 to 1996 time period can be either helpful or harmful to urban
      hospitals. A strategic change that contributes positively to one type of
      performance can negatively impact the other. CONCLUSIONS: Although differences of
      opinion persist in the strategic change debate, results of this study indicate
      that strategic change can be helpful or harmful to urban hospitals, and its
      consequences are far more complex than previously thought. Strategic rationality
      has its own limitations and cannot always be relied on to yield expected results.
      Hospital strategic changes require coordination to achieve greater performance
      results.

PMID- 11949919
TI  - Family structure, socioeconomic status, and access to health care for children.
AB  - OBJECTIVE: To test the hypothesis that among children of lower socioeconomic
      status (SES), children of single mothers would have relatively worse access to
      care than children in two-parent families, but there would be no access
      difference by family structure among children in higher SES families. DATA
      SOURCES: The National Health Interview Surveys of 1993-95, including 63,054
      children. STUDY DESIGN: Logistic regression was used to examine the relationship
      between the child's family structure (single-mother or two-parent family) and
      three measures of health care access and utilization: having no physician visits
      in the past year, having no usual source of health care, and having unmet health
      care needs. To examine how these relationships varied at different levels of SES,
      the models were stratified on maternal education level as the SES variable. The
      stratified models adjusted for maternal employment, child's health status, race
      and ethnicity, and child's age. Models were fit to examine the additional effects
      of health insurance coverage on the relationships between family structure,
      access to care, and SES. PRINCIPAL FINDINGS: Children of single mothers, compared
      with children living with two parents, were as likely to have had no physician
      visit in the past year; were slightly more likely to have no usual source of
      health care; and were more likely to have an unmet health care need. These
      relationships differed by mother's education. As expected, children of single
      mothers had similar access to care as children in two-parent families at high
      levels of maternal education, for the access measures of no physician visits in
      the past year and no usual source of care. However, at low levels of maternal
      education, children of single mothers appeared to have better access to care than
      children in two-parent families. Once health insurance was added to adjusted
      models, there was no significant socioeconomic variation in the relationships
      between family structure and physician visits or usual source of care, and there
      were no significant disparities by family structure at the highest levels of
      maternal education. There were no family structure differences in unmet needs at
      low maternal education, whereas children of single mothers had more unmet needs
      at high levels of maternal education, even after adjustment for insurance
      coverage. CONCLUSIONS: At high levels of maternal education, family structure did
      not influence physician visits or having a usual source of care, as expected.
      However, at low levels of maternal education, single mothers appeared to be
      better at accessing care for their children. Health insurance coverage explained
      some of the access differences by family structure. Medicaid is important for
      children of single mothers, but children in two-parent families whose mothers are
      less educated do not always have access to that resource. Public health insurance
      coverage is critical to ensure adequate health care access and utilization among
      children of less educated mothers, regardless of family structure.

PMID- 11949920
TI  - Development of a scale to measure patients' trust in health insurers.
AB  - OBJECTIVE: To develop a scale to measure patients' trust in health insurers,
      including public and private insurers and both indemnity and managed care. A
      scale was developed based on our conceptual model of insurer trust. The scale was
      analyzed for its factor structure, internal consistency, construct validity, and
      other psychometric properties. DATA SOURCES/STUDY SETTING: The scale was
      developed and validated on a random national sample (n = 410) of subjects with
      any type of insurance and further validated and used in a regional random sample
      of members of an HMO in North Carolina (n = 1152). STUDY DESIGN: Factor analysis
      was used to uncover the underlying dimensions of the scale. Internal consistency
      was assessed by Cronbach's alpha. Construct validity was established by Pearson
      or Spearman correlations and t tests. DATA COLLECTION: Data were collected via
      telephone interviews. PRINCIPAL FINDINGS: The 11-item scale has good internal
      consistency (alpha = 0.92/ 0.89) and response variability (range = 11-55, M =
      36.5/37.0, SD = 7.8/7.0). Insurer trust is a unidimensional construct and is
      related to trust in physicians, satisfaction with care and with insurer, having
      enough choice in selecting health insurer, no prior disputes with health insurer,
      type of insurer, and desire to remain with insurer. CONCLUSIONS: Trust in health
      insurers can be validly and reliably measured. Additional studies are required to
      learn more about what factors affect insurer trust and whether differences and
      changes in insurer trust affect actual behaviors and other outcomes of interest.

PMID- 11949921
TI  - Methodologic implications of allocating multiple-race data to single-race
      categories.
AB  - OBJECTIVE: To illustrate methods for comparing race data collected under the 1977
      Federal Office of Management and Budget (OMB) directive, known as OMB-15, with
      race data collected under the revised 1997 OMB standard. DATA SOURCES/STUDY
      SETTING: Secondary data from the 1993-95 National Health Interview Surveys.
      Multiple-race responses, available on in-house files, were analyzed. STUDY
      DESIGN: Race-specific estimates of employer-sponsored health insurance were
      calculated using proposed allocation methods from the OMB. Estimates were
      calculated overall and for three population subgroups: children, those in
      households below poverty, and Hispanics. PRINCIPAL FINDINGS: Although race
      distributions varied between the different methods, estimates of employer
      sponsored health insurance were similar. Health insurance estimates for the
      American Indian/Alaska Native group varied the most. CONCLUSIONS: Employer
      sponsored health insurance estimates for American Indian/Alaska Natives from data
      collected under the 1977 OMB directive will not be comparable with estimates from
      data collected under the 1997 standard. The selection of a method to distribute
      to the race categories used prior to the 1997 revision will likely have little
      impact on estimates of employer-sponsored health insurance for other groups.
      Additional research is needed to determine the effects of these methods for other
      health service measures.

PMID- 11949922
TI  - Characterizing patient requests and physician responses in office practice.
AB  - OBJECTIVE: To assess the reliability, applicability, and validity of a refined
      system (taxonomy of requests by patients [TORP]) for characterizing patient
      requests and physician responses in office practice. STUDY SETTINGS: Data were
      obtained from visits to six general internists practicing in North-Central
      California in 1994 and eight cardiologists practicing in the same region in 1998.
      STUDY DESIGN: This was an observational study of patient requests and physician
      responses in two practice settings. Patients were surveyed before and after the
      visit. Physicians were surveyed immediately after the visit, and all visits were
      audio recorded for future study. DATA COLLECTION/EXTRACTION METHODS: TORP was
      refined using input from a multidisciplinary panel. Audiotape recordings of 131
      visits (71 in internal medicine and 60 in cardiology) were rated independently by
      two coders. Estimates of classifying reliability (intercoder agreement on the
      sorting of requests into categories) and unitizing reliability (intercoder
      agreement on the labeling of elements of discourse as "requests" and subsequent
      classification into categories) were calculated. Validity was assessed by testing
      three specific hypotheses concerning the antecedents and consequences of patient
      requests and request fulfillment. PRINCIPAL FINDINGS: The overall unitizing kappa
      for identifying patients' requests was 0.64, and the classification kappa was
      0.73, indicating substantial agreement beyond chance. The average patient made
      4.19 requests for information and 0.88 requests for physician action; there were
      few differences in the spectrum of requests between internal medicine and
      cardiology. Approximately 15 percent of visits included a direct request for
      completion of paperwork. Patients who were very or extremely worried about their
      health made more requests than those who were not (6.06 vs. 3.89, p < 0.05).
      Visits involving more patient requests took longer (p < 0.05) and were perceived
      as more demanding by the treating physician (p = 0.025). The vast majority of
      requests were fulfilled. CONCLUSIONS: The refined TORP shows evidence of both
      unitizing and classification reliability and should be a useful tool for
      understanding the clinical negotiation. In addition, the system appears
      applicable to both generalist and specialist practices. More experience with the
      system is necessary to appraise TORP's ability to predict important clinical
      outcomes.

PMID- 11949923
TI  - The health services researcher, multiple identities.

PMID- 11949924
TI  - State coverage expansions: learning from research and practice.

PMID- 11949925
TI  - Health insurance knowledge among Medicare beneficiaries.
AB  - OBJECTIVE: To assess the effect of new consumer information materials about the
      Medicare program on beneficiary knowledge of their health care coverage under the
      Medicare system. DATA SOURCE: A telephone survey of 2,107 Medicare beneficiaries
      in the 10-county Kansas City metropolitan statistical area. STUDY DESIGN:
      Beneficiaries were randomly assigned to a control group and three treatment
      groups each receiving a different set of Medicare informational materials. The
      "handbook-only" group received the Health Care Financing Administration's new
      Medicare & You 1999 handbook. The "bulletin" group received an abbreviated
      version of the handbook, and the "handbook + CAHPS" group received the Medicare &
      You handbook plus the Consumer Assessment of Health Plans (CAHPS) survey report
      comparing the quality of health care provided by Medicare HMOs. Beneficiaries
      interested in receiving information were oversampled. DATA COLLECTION METHODS:
      Data were collected during two separate telephone surveys of Medicare
      beneficiaries: one survey of new beneficiaries and another survey of experienced
      beneficiaries. The intervention materials were mailed to sample members in
      advance of the interviews. Knowledge for the treatment groups was measured
      shortly after beneficiaries received the intervention materials. PRINCIPAL
      FINDINGS: Respondents' knowledge was measured using a psychometrically valid and
      reliable 15-item measure. Beneficiaries who received the intervention materials
      answered significantly more questions correctly than control group members. The
      effect on beneficiary knowledge of providing the information was modest for all
      intervention groups but varied for experienced beneficiaries only, depending on
      the intervention they received. CONCLUSIONS: The findings suggest that all of the
      new materials had a positive effect on beneficiary knowledge about Medicare and
      the Medicare + Choice program. While the absolute gain in knowledge was modest,
      it was greater than increases in knowledge associated with traditional Medicare
      information sources.

PMID- 11949927
TI  - Health services research: an evolving definition of the field.

PMID- 11949926
TI  - Delivery of preventive health services for breast cancer control: a longitudinal
      view of a randomized controlled trial.
AB  - OBJECTIVE: To develop a longitudinal model to characterize the delivery of
      mammography services using repeated observations of mammography referral rates
      during a randomized controlled trial (RCT) of physician mammography reminders.
      DATA SOURCES/STUDY SETTING: Administrative records of a health department and
      observational data on mammography appointment scheduling. STUDY DESIGN: The
      design was a longitudinal study of month-specific referral rates during a 1-year
      RCT. A retrospective case-control study was used to investigate differences
      between women with timely and delayed (or absent) mammography referral assessed
      at the end of the intervention year. DATA COLLECTION/EXTRACTION METHODS: Month
      specific indicators for referrals and missed clinical opportunities, that is,
      months when clinic visitors were due for a mammogram and not referred, were
      constructed using administrative and observational data. FINDINGS: In the
      unadjusted analysis, the effectiveness of the reminder declined over time.
      However, in a multivariate analysis that controlled for the number of missed
      opportunities, the effectiveness was constant over time. On a monthly basis,
      physician reminders were significantly associated with higher referral rates
      among clinic visitors newly due for mammography (adjusted OR = 2.8, 95 percent CI
      = 1.3, 5.8) or who had one previously missed clinical opportunity (adjusted OR =
      3.0, 95 percent CI = 1.6, 5.3) but were not for those with two or more missed
      clinical opportunities (adjusted OR = 1.2, 95 percent CI = 0.7, 2.3). Factors
      independently associated with delayed referral were age over 65, presence of more
      than one chronic illness, and the absence of a physician mammography reminder.
      CONCLUSIONS: Longitudinal models that examine rates of referral over time and
      include information about outcomes on previous visits can enhance our
      understanding of how intervention strategies work in practice.

PMID- 11949928
TI  - Access to health care and community social capital.
AB  - OBJECTIVE: To test the hypothesis that variation in reported access to health
      care is positively related to the level of social capital present in a community.
      DATA SOURCES: The 1996 Household Survey of the Community Tracking Study, drawn
      from 22 metropolitan statistical areas across the United States (n = 19,672).
      Additional data for the 22 communities are from a 1996 multicity broadcast media
      marketing database, including key social capital indicators, the 1997 National
      Profile of Local Health Departments survey, and Interstudy, American Hospital
      Association, and American Medical Association sources. STUDY DESIGN: The design
      is cross-sectional. Self-reported access to care problems is the dependent
      variable. Independent variables include individual sociodemographic variables,
      community-level health sector variables, and social capital variables. DATA
      COLLECTION/EXTRACTION METHODS: Data are merged from the various sources and
      weighted to be population representative and are analyzed using hierarchical
      categorical modeling. PRINCIPAL FINDINGS: Persons who live in metropolitan
      statistical areas featuring higher levels of social capital report fewer problems
      accessing health care. A higher HMO penetration rate in a metropolitan
      statistical area was also associated with fewer access problems. Other health
      sector variables were not related to health care access. CONCLUSIONS: The results
      observed for 22 major U.S. cities are consistent with the hypothesis that
      community social capital enables better access to care, perhaps through improving
      community accountability mechanisms.

PMID- 11949929
TI  - Putting practice into research.

PMID- 11949931
TI  - Type I glycogen storage diseases: disorders of the glucose-6-phosphatase complex.
AB  - Glycogen storage disease type I (GSD-I) is a group of autosomal recessive
      disorders with an incidence of 1 in 100,000. The two major subtypes are GSD-Ia
      (MIM232200), caused by a deficiency of glucose-6-phosphatase (G6Pase), and GSD-Ib
      (MIM232220), caused by a deficiency in the glucose-6-phosphate transporter
      (G6PT). Both G6Pase and G6PT are associated with the endoplasmic reticulum (ER)
      membrane. G6PT translocates glucose-6-phosphate (G6P) from the cytoplasm into the
      lumen of the ER, where G6Pase hydrolyses the G6P into glucose and phosphate.
      Together G6Pase and G6PT maintain glucose homeostasis. G6Pase is expressed in
      gluconeogenic tissues, the liver, kidney, and intestine. However G6PT, which
      transports G6P efficiently only in the presence of G6Pase, is expressed
      ubiquitously. This suggests that G6PT may play other roles in tissues lacking
      G6Pase. Both GSD-Ia and GSD-Ib patients manifest phenotypic G6Pase deficiency,
      characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly,
      hyperlipidemia, hyperuricemia, and lactic academia and the current treatment is a
      dietary therapy. GSD-Ib patients also suffer from chronic neutropenia and
      functional deficiencies of neutrophils and monocytes, which is treated with
      granulocyte colony stimulating factor to restore myeloid function. The GSD-Ia and
      GSD-Ib genes have been cloned. To date, 76 G6Pase and 69 G6PT mutations have been
      identified in GSD-I patients. A database of the residual enzymatic activity
      retained by the G6Pase missense mutants is facilitating the correlation of the
      disease phenotype with the patients' genotype. While the molecular basis for the
      GSD-I disorders are now known and symptomatic therapies are available, many
      aspects of the diseases are still poorly understood, and there are no cures.
      Recently developed animal models of the disorders are now being exploited to
      delineate the disease more precisely and develop new, more causative therapies.

PMID- 11949930
TI  - Glycogen and its metabolism.
AB  - Glycogen is a branched polymer of glucose which serves as a reservoir of glucose
      units. The two largest deposits in mammals are in the liver and skeletal muscle
      but many cells are capable synthesizing glycogen. Its accumulation and
      utilization are under elaborate controls involving primarily covalent
      phosphorylation and allosteric ligand binding. Both muscle and liver glycogen
      reserves are important for whole body glucose metabolism and their replenishment
      is linked hormonally to nutritional status. Control differs between muscle and
      liver in part due to the existence of different tissue-specific isoforms at key
      steps. Control of synthesis is shared between transport into the muscle and the
      step catalyzed by glycogen synthase. Breakdown of liver glycogen, as part of
      blood glucose homeostasis, is also in response to nutritional cues. Muscle
      glycogen serves only to fuel muscular activity and its utilization is controlled
      by muscle contraction and by catecholamines. Though the number of enzymes
      directly involved in the metabolism of glycogen is quite small, many more
      proteins act indirectly in a regulatory capacity. Defects in the basic
      metabolizing enzymes lead to severe consequences whereas, with some exceptions,
      mutations in the regulatory proteins appear to cause a more subtle phenotypic
      change.

PMID- 11949932
TI  - Acid alpha-glucosidase deficiency (glycogenosis type II, Pompe disease).
AB  - Glycogenosis type II (GSDII, Pompe disease) is an autosomal recessive lysosomal
      storage disease caused by a deficiency of acid alpha-glucosidase (acid maltase,
      GAA). The enzyme degrades alpha -1,4 and alpha -1,6 linkages in glycogen,
      maltose, and isomaltose. Deficiency of the enzyme results in accumulation of
      glycogen within lysosomes and in cytoplasm eventually leading to tissue
      destruction. The discovery of the acid a-glucosidase gene has led to rapid
      progress in understanding the molecular basis of glycogenosis type II and the
      biological properties of the GAA protein. The last decade has seen several
      developments: 1) extensive mutational analysis in patients with different forms
      of the disease, 2) characterization of the enzyme biosynthesis, processing, and
      lysosomal targeting, 3) generation of knockout mouse models, 4) development of
      viral vectors for gene replacement therapy, 5) the production of recombinant
      human enzyme, and 6) a shift in the enzyme replacement therapy approach from
      theory to practice. It is anticipated that the enzyme replacement therapy will be
      widely available for human use in the near future. Several recent reviews
      (including the most comprehensive one by R. Hirschhorn and A. Reuser [1]),
      address clinical, biochemical and genetic aspects of the disease, as well as
      development of new therapies for GSDII [2, 3, 4]. In this article we will review
      recent findings in the area including rapidly accumulating molecular genetic data
      (more than 20 mutations need to be added to the list), transcriptional control of
      gene expression, studies in mouse models, and new approaches to gene therapy. We
      will also highlight some emerging questions following the introduction of enzyme
      replacement therapy.

PMID- 11949933
TI  - Molecular characterization of glycogen storage disease type III.
AB  - Deficiency of the glycogen debranching enzyme (gene, AGL) causes glycogen storage
      disease type III (GSD-III), an autosomal recessive disease affecting glycogen
      metabolism. Most GSD-III patients have AGL deficiency in both the liver and
      muscle (type IIIa), but some have it in the liver but not muscle (type IIIb).
      Cloning of human AGL cDNAs and determination of the genomic structure and mRNA
      isoforms of AGL have allowed for the study of GSD-III at the molecular level. In
      turn, the resulting information has greatly facilitated our understanding of the
      molecular basis of this storage disease with remarkable clinical and enzymatic
      variability. In this review, we summarize all 31 GSD-III mutations in the
      literature and discuss their clinical and laboratory implications. Most of the
      mutations are nonsense mutations caused by a nucleotide substitution or small
      insertion or deletion; only one is caused by a missense amino acid change. Some
      important genotype-phenotype correlation have emerged, in particular, that exon 3
      mutations (17delAG and Q6X) are specifically associated with GSD-IIIb. Three
      other mutations have appeared to have some phenotype correlation. Specifically,
      the splice mutation IVS32-12A>G was found in GSD-III patients having mild
      clinical symptoms, while the mutations 3965delT and 4529insA are associated with
      a severe phenotype and early onset of clinical manifestations. A molecular
      diagnostic scheme has been proposed to diagnose GSD-III noninvasively. The
      characterization of AGL mutations in GSD-III patients has also helped the
      structure-function analysis of this bifunctional enzyme important for glycogen
      metabolism.

PMID- 11949934
TI  - The variable presentations of glycogen storage disease type IV: a review of
      clinical, enzymatic and molecular studies.
AB  - Glycogen storage disease type IV (GSD-IV), also known as Andersen disease or
      amylopectinosis (MIM 23250), is a rare autosomal recessive disorder caused by a
      deficiency of glycogen branching enzyme (GBE) leading to the accumulation of
      amylopectin-like structures in affected tissues. The disease is extremely
      heterogeneous in terms of tissue involvement, age of onset and clinical
      manifestations. The human GBE cDNA is approximately 3-kb in length and encodes a
      702-amino acid protein. The GBE amino acid sequence shows a high degree of
      conservation throughout species. The human GBE gene is located on chromosome 3p14
      and consists of 16 exons spanning at least 118 kb of chromosomal DNA. Clinically
      the classic Andersen disease is a rapidly progressive disorder leading to
      terminal liver failure unless liver transplantation is performed. Several
      mutations have been reported in the GBE gene in patients with classic phenotype.
      Mutations in the GBE gene have also been identified in patients with the milder
      non-progressive hepatic form of the disease. Several other variants of GSD-IV
      have been reported: a variant with multi-system involvement including skeletal
      and cardiac muscle, nerve and liver; a juvenile polysaccharidosis with multi
      system involvement but normal GBE activity; and the fatal neonatal neuromuscular
      form associated with a splice site mutation in the GBE gene. Other presentations
      include cardiomyopathy, arthrogryposis and even hydrops fetalis. Polyglucosan
      body disease, characterized by widespread upper and lower motor neuron lesions,
      can present with or without GBE deficiency indicating that different biochemical
      defects could result in an identical phenotype. It is evident that this disease
      exists in multiple forms with enzymatic and molecular heterogeneity unparalleled
      in the other types of glycogen storage diseases.

PMID- 11949935
TI  - Myophosphorylase deficiency (glycogenosis type V; McArdle disease).
AB  - McArdle disease, one of the most common metabolic causes of exercise intolerance
      and recurrent myoglobinuria, is due to biochemical defects of the muscle isoform
      of glycogen phosphorylase. The gene for myophosphorylase (PGYM) is on chromosome
      11, and 33 distinct mutations have been identified in patients from all over the
      world. In Caucasians, a nonsense mutation in exon 1 (R49X) is common enough to
      warrant screening of genomic DNA from blood before considering muscle biopsy.
      Other mutations are prevalent in different ethnic groups or are "private".
      Mutations are spread throughout the gene and there is no clear genotype:phenotype
      correlation. High-protein diet and aerobic exercise are beneficial, and gene
      therapy appears promising.

PMID- 11949936
TI  - Phosphofructokinase deficiency; past, present and future.
AB  - Phosphofructokinase deficiency (Tarui disease, glycogen storage disease VII, GSD
      VII) stands out among all the GSDs. PFK deficiency was the first recognized
      disorder that directly affects glycolysis. Ever since the discovery of the
      disease in 1965, a wide range of biochemical, physiological and molecular studies
      of the disorder have greatly expanded our understanding of the function of normal
      muscle, general control of glycolysis and glycogen metabolism. The studies of PFK
      deficiency vastly enriched the field of glycogen storage diseases, as well as the
      field of metabolic and neuromuscular disorders. This article cites a historical
      overview of this clinical entity and the progress that has been made in molecular
      genetic area. We will also present the results of a search in-silico, which
      allowed us to identify a previously unknown sequence of the human platelet PFK
      gene (PFK-P). In addition, we will describe phylogenetic analysis of evolution of
      PFK genes.

PMID- 11949938
TI  - Clinical aspects of endometriosis.
AB  - Endometriosis is one of the most commonly encountered gynecologic diseases
      requiring medical and/or surgical therapy. It is a leading cause of hysterectomy
      in the United States and has significant associated morbidity. The most frequent
      symptoms of genital tract endometriosis are dysmenorrhea, dyspareunia, chronic
      pelvic pain, and infertility. Endometriosis occurs in the pelvis, most commonly
      the ovaries and the dependent areas covered with peritoneum. Diagnosis requires
      surgical intervention and is usually made by laparoscopy. In women being
      evaluated for pelvic pain, the diagnosis of endometriosis is made frequently (40
      60%) and varies with the population being studied. Infertility and endometriosis
      have long been associated. Although women with infertility may have pelvic pain,
      subfertility (20-30%) can be the only presenting symptom. In asymptomatic women,
      the diagnosis of endometriosis ranges from 2% to 22% of reproductive-age women.
      Its true incidence and natural history remain to be clarified. Endometriosis is a
      significant public health issue because of the large number of women it affects
      and the significant morbidity associated with this disease.

PMID- 11949937
TI  - Fanconi-Bickel syndrome--a congenital defect of facilitative glucose transport.
AB  - Fanconi-Bickel syndrome (FBS, OMIM 227810) is a rare type of glycogen storage
      disease (GSD). It is caused by homozygous or compound heterozygous mutations
      within GLUT2, the gene encoding the most important facilitative glucose
      transporter in hepatocytes, pancreatic beta-cells, enterocytes, and renal tubular
      cells. To date, 112 patients have been reported in the literature. Most patients
      have the typical combination of clinical symptoms: hepatomegaly secondary to
      glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a
      characteristic tubular nephropathy, and severely stunted growth. In 63 patients,
      mutation analysis has revealed a total of 34 different GLUT2 mutations with none
      of them being particularly frequent. No specific therapy is available for FBS
      patients. Symptomatic treatment is directed towards a stabilization of glucose
      homeostasis and compensation for renal losses of various solutes. In addition to
      the clinical and molecular genetic aspects of FBS, this review discusses the
      pathophysiology of the disease and compares it to recent findings in GLUT2
      deficient transgenic animals. An overview is also provided on recently discovered
      members of the rapidly growing family of facilitative glucose transporters, which
      are novel candidates for congenital disorders of carbohydrate metabolism.

PMID- 11949939
TI  - Local cytokines in endometrial tissue: the role of interleukin-8 in the
      pathogenesis of endometriosis.
AB  - Endometriosis, defined by the presence of viable endometrial tissue outside the
      uterine cavity, is among the most common gynecologic disorders affecting women of
      reproductive age. Endometriosis is associated with an inflammatory peritoneal
      environment, where multiple cytokines and growth factors are found at elevated
      levels. Interleukin-8 (IL-8) is a cytokine that induces chemotaxis of neutrophils
      and is a potent angiogenic agent. In addition, IL-8 was recently found to
      stimulate proliferation of various cells. We have observed that IL-8 is elevated
      in the peritoneal fluid of women with endometriosis and the levels correlate with
      the severity of the disease. We hypothesized that IL-8 may play a role in the
      growth and maintenance of ectopic endometrial tissue not only by chemoattracting
      and stimulating leukocytes to secrete growth factors and cytokines, but also by
      directly affecting endometrial cell proliferation. We found that IL-8 mRNA and
      protein levels in the endometrium were significantly higher during early
      proliferative and late secretory phases than during the mid-cycle. IL-8 receptors
      A and B are also expressed in the endometrium mostly localized in the stroma.
      Interestingly, IL-8 receptor expression is higher in the eutopic endometrium of
      women with endometriosis compared to the endometrium of women without
      endometriosis. Endometrial cells in culture proliferate significantly when
      treated with IL-8, which is inhibited by anti-IL-8 neutralizing antibody. More
      convincingly, IL-8 antisense oligonucleotide treatment decreases IL-8 production
      by endometrial cells as well as cell proliferation when compared to non-sense
      oligonucleotide treatment. The addition of IL-8 reverses the inhibitory effect of
      IL-8 antisense oligonucleotides on cell proliferation. These findings suggest
      that IL-8 may act as an autocrine growth factor in the endometrium. We have also
      studied the effect of endometrial cell adhesion on IL-8 expression and observed
      that IL-8 stimulates the adhesion of endometrial cells to fibronectin. Treatment
      of the cells with anti-IL-8 neutralizing antibody inhibited partially the cell
      adhesion. Thus, IL-8 may also be relevant for stimulating the attachment of
      endometrial implants in the pathogenesis of endometriosis. In addition, adherence
      of endometrial cells induced further IL-8 expression by an integrin-dependent
      mechanism. In summary, IL-8 may act as an autocrine growth factor in the
      endometrium and may also play a role in the pathogenesis of endometriosis by
      promoting the vicious circle of endometrial cell attachment, cell growth, and
      further secretion of this cytokine.

PMID- 11949940
TI  - The epidemiology of endometriosis.
AB  - Advances in understanding the epidemiology of endometriosis have lagged behind
      other diseases because of methodologic problems related to disease definition and
      control selection. Nevertheless, a better picture of the epidemiology of
      endometriosis has emerged over the past few decades. Prevalence estimates of the
      disease in clinic populations vary from about a 4% occurrence of largely
      asymptomatic endometriosis found in women undergoing tubal ligation to 50% of
      teenagers with intractable dysmenorrhea. General population incidence during the
      1970s in this country has been suggested to be 1.6 per 1000 white females aged 15
      49, while a more current study based upon hospital discharges finds endometriosis
      as a first listed diagnosis in 1.3 per 1000 discharges in women aged 15-44. There
      is a clinical impression that blacks have lower rates of endometriosis and
      Orientals have higher rates than whites. A variety of personal risk factors for
      endometriosis have also been described. Women with endometriosis may be taller
      and thinner. Menstrual factors reported to increase risk include dysmenorrhea,
      early menarche, and shorter cycle lengths. There is support for the idea that
      lifestyle exposures that might raise or lower estrogen levels could affect risk,
      including a decreased risk associated with smoking and exercise and an increased
      risk associated with caffeine or alcohol use. These risk factors appear to be
      compatible with the central importance of retrograde menstruation influenced by
      outflow obstruction that might affect its amount, immune factors that might
      affect its ability to be cleared, or hormonal stimuli that might affect its
      growth. In this model, dysmenorrhea could be either a disease symptom or a
      manifestation of outflow obstruction. Nulliparity could be either a consequence
      of disease or a cause since nulliparous women would not have the benefit of
      cervical dilation associated with labor and delivery. Since there is evidence
      that family history is a risk factor for disease, a challenge is how to integrate
      genetic factors into the model. The genetics of endometriosis might be advanced
      if we could identify an "endometriosis phenotype". We propose that this may
      consist of early menarche, short cycles, painful periods, subfertility, and
      possibly tall stature that could be explained by genetic factors that predispose
      to poor endowment of germ cells and canalization defects of the cervix. The value
      of establishing an "endometriosis phenotype" is that, as candidates for genetic
      markers are identified, particular genotypes can be correlated with these factors
      even if a formal diagnosis of endometriosis has not been made. Additional well
      designed case-control and cohort studies will be necessary to test theories
      related to pathogenesis, establish the precise relationship between reproductive
      morbidity and endometriosis, identify specific genetic factors, and establish
      long-term risks.

PMID- 11949941
TI  - Control of growth and differentiation of the endometrium: the role of tissue
      interactions.
AB  - Early work with neonatal mice showed that estrogen receptor-negative uterine
      epithelium responded to estrogen treatment. Since the underlying mesenchymal
      cells were estrogen receptor-positive, it was suggested that these cells mediated
      the hormonal response through elaboration of a paracrine factor. Cell culture
      work showed that mesenchymal cells produced soluble factors that stimulate
      uterine epithelium, but hormonal regulation was absent or minimal. The paracrine
      hypothesis of estrogen action has been proved by the use of tissue recombinant
      studies in which epithelium from estrogen receptor-alpha knockout mice was
      combined with wild-type mesenchyme; estrogen stimulated the ER alpha-negative
      epithelium if the underlying stromal cells were receptor-positive. Also, it is
      hypothesized that there is a reciprocal paracrine interaction during stimulation
      with progesterone and estrogen. Accordingly, under progesterone dominance, the
      epithelium elaborates factors that direct the underlying stroma to proliferate
      when estrogen is administered. Although this hypothesis needs further testing, it
      has been shown that the uterine epithelium is required for stromal responsiveness
      to hormones. The question arises: What are the factors that mediate the effects
      of the steroid hormones in the uterus? Several peptide growth factors are
      regulated by estrogen and/or progesterone. Use of knockout animals will allow a
      determination of the role that these factors play in the uterus. However,
      ablation of many of these growth factor genes has proved lethal to the newborn
      animals, making it impossible to study hormonal effects using standard
      techniques. Tissue xenograft and tissue recombination studies offer a means of
      defining the role of specific growth factors in uterine physiology.

PMID- 11949942
TI  - Circulating ovarian steroids and endometrial matrix metalloproteinases (MMPs).
AB  - Recent studies strongly suggest that matrix metalloproteinases (MMPs) play a key
      role in the initiation of menstrual bleeding in the human endometrium upon the
      fall of ovarian steroid serum concentrations by inducing the degradation of the
      extracellular matrix of this mucosa. MMPs are also involved in abnormal
      endometrial bleeding and have been identified in endometriotic foci. In all
      cases, they are associated with areas of extracellular matrix breakdown. This
      paper reviews the literature on the regulation by estradiol and progesterone of
      the expression and activation of MMPs, and of the expression of their tissue
      inhibitors (TIMPs), (i) in the endometrium in situ during normal cycle, (ii)
      during artificial cycles in spayed monkeys, and (iii) in cultures of endometrial
      explants or purified cells. Whereas progesterone consistently decreases the
      activity of endometrial MMPs, its effects vary in intensity, duration, and
      pattern between MMPs as well as among experimental systems. The contribution and
      limitations of the various investigations are therefore discussed. The focal
      heterogeneity points to additional local controls of the expression and
      activation of MMPs in human endometrium, acting beyond the general inhibitory
      role of progesterone, for example, by cytokines. Focal changes in type or
      abundance of sex steroid receptors also could be responsible for spatial
      variation in the expression of MMPs in the endometrium and endometriotic lesions.

PMID- 11949943
TI  - Paracrine mediators of endometrial matrix metalloproteinase expression: potential
      targets for progestin-based treatment of endometriosis.
AB  - The endometrial lining of the human uterus is a highly specialized, steroid
      sensitive tissue. Throughout the reproductive years, the endometrium undergoes
      dramatic cycles of growth, differentiation, and breakdown under the influence of
      ovarian steroids. In response to changes in steroid exposure throughout the
      menstrual cycle, the endometrium produces an array of bioactive growth factors
      and other cytokines that are critical components of paracrine communication. For
      example, cell-cell communication via paracrine factors directs the expression of
      matrix metalloproteinases (MMPs), enzymes that mediate tissue remodeling during
      the menstrual cycle. The disease endometriosis is thought to occur as a
      consequence of retrograde menstruation, and MMPs appear to contribute to the
      establishment and progression of ectopic endometrial growth in the peritoneal
      cavity. Although the risk for developing endometriosis is linked to a woman's
      steroid exposure, locally produced paracrine factors can modify steroid action on
      multiple gene targets, including the MMPs. Estrogen-associated growth factors as
      well as inflammatory cytokines are potent stimulators of MMP expression and may
      contribute to the ability of endometrial fragments to invade the peritoneal
      surface and establish ectopic sites of growth. In contrast, paracrine factors
      associated with progesterone action during early pregnancy inhibit MMP expression
      and prevent ectopic endometrial growth in an experimental model. For example,
      locally produced retinoic acid and transforming growth factor-beta (TGF-beta) act
      in concert with progesterone to suppress MMPs, while enhancing expression of MMP
      inhibitors (TIMPs) during endometrial differentiation. Targeting pregnancy
      associated factors that inhibit endometrial-specific MMP expression and action
      may enhance the effectiveness of progestin-related treatments for endometriosis.

PMID- 11949944
TI  - Paracrine regulation of matrix metalloproteinase expression in endometriosis.
AB  - Following retrograde menstruation, shed endometrial tissue fragments attach to
      and invade the peritoneal surface to form established endometriotic lesions. With
      disease progression, the biochemically active lesions undergo remodeling and
      become fibrotic. Matrix metalloproteinase enzymes (MMPs) and the tissue
      inhibitors of metalloproteinases (TIMPs) play a significant role in normal
      endometrial remodeling during menses. Anomalous expression of MMPs and TIMPs has
      been identified in endometriotic lesions as compared to their highly regulated
      expression in eutopic endometrium. The paracrine mechanisms regulating
      misexpression of MMPs and TIMPs by endometriotic lesions are, however, not well
      defined. Misexpression of the MMPs and TIMPs may be due to innate anomalies in
      the eutopic endometrium from women with endometriosis, in the resident immune
      cells and peritoneal cells that juxtapose the ectopic endometrium, and/or
      numerous substances present in peritoneal fluid of women with endometriosis. The
      majority of MMPs are under strict transcriptional regulation. Steroid hormones
      and cytokines appear to act on the MMP promoter, either independently or in
      consort, to provide both positive and negative regulation of these genes.
      Misregulated expression of MMPs and TIMPs is associated with a more aggressive
      phenotype and a cascade of events facilitating peritoneal extracellular matrix
      degradation and establishment or remodeling of endometriotic lesions. The
      mechanisms by which MMP and TIMP expression are misregulated warrant further
      investigation as such information may provide insight into novel therapeutic
      modalities for endometriosis.

PMID- 11949945
TI  - Regulation and modulation of abnormal immune responses in endometriosis.
AB  - There is ample evidence demonstrating that endometriosis is accompanied by
      inflammatory reactions in the peritoneum, resulting in abnormal levels of a
      variety of cytokines and chemokines in the peritoneal fluid. Among the
      immunological parameters that have been shown to be altered in the peritoneal
      cavity of women with endometriosis, an increase in the number of activated
      nonadherent macrophages that show reduced surface expression of scavenger
      receptors has been observed. The cause-and-effect relationship between aberrant
      peritoneal macrophage activity and endometriosis is still unknown. We have
      demonstrated that steroid hormone receptor agonists and antagonists [e.g.,
      retinoids, antiglucocorticoids, ligands to peroxisome proliferator activated
      receptors (PPARs)] can regulate macrophage functions in ways that could either
      suppress or stimulate the growth of ectopic endometrial lesions. Our studies
      include a number of relevant findings: (1) RU486, acting as an antioxidant, can
      suppress activation of NFkappaB, a nuclear transcription factor that affects the
      expression of several inflammatory genes such as those for MCP-1, GM-CSF, CSF-1,
      and various adhesion molecules; (2) IL-6 secretion from a variety of cell types
      including endometrial cells is inhibited by retinoic acid; and (3) retinoids and
      PPARgamma ligands can upregulate the expression of scavenger receptors in cells
      of the monocyte/macrophage lineage. These observations, combined with the
      possibility that macrophage activity may play a fundamental role in
      endometriosis, suggest that pharmacologic manipulation of macrophage function may
      provide a novel mechanism for treating this disease.

PMID- 11949946
TI  - Autoantibody responses to carbohydrate epitopes in endometriosis.
AB  - Autoantibody responses to endometrial and serum antigens are a common feature of
      endometriosis. We have shown that the serum autoantibody response in
      endometriosis to a number of previously identified antigens, including alpha2
      Heremans Schmidt glycoprotein and carbonic anhydrase, is specific for a
      carbohydrate epitope common to these proteins. Removal of carbohydrate moieties
      from these antigens resulted in a loss of antibody binding. Antibody reactivity
      was abolished following adsorption with the lectin jacalin, which specifically
      binds the Thomsen-Friedenreich (T) antigen (Gal beta1-3GalNAc). Demonstration
      that the autoantibodies also reacted with other Thomsen-Friedenreich antigen
      bearing proteins, such as serum IgA1, hemopexin, and MMP-9, confirmed that this
      glycotope is involved in the autoantibody response. However, the autoantibody
      binding requires the presence of at least one sialic acid residue. Thus, the
      glycotope involved may be a sialylated T antigen. These findings allow us to
      hypothesize a number of mechanisms whereby the autoimmune response plays a direct
      role in several aspects of the disease process. The proposed mechanisms take into
      account the salient endocrine dependency of endometriotic lesions and other
      aspects of the disease process such as aberrant matrix metalloproteinase function
      and the ability of endometrial cells to implant at ectopic sites. The anti-T-like
      response may also be indicative of an underlying genetic defect in glycosylation
      or in the control of glycosylation by steroid sex hormones. Further
      characterization of this autoimmune response may prove useful in the development
      of serum-based diagnostic tests for endometriosis and may lead to the development
      of therapeutic strategies.

PMID- 11949947
TI  - Macrophages, oxidation, and endometriosis.
AB  - Retrograde menstruation has been suggested to be the cause for the presence of
      endometrial cells in the peritoneal cavity. However, little is known about the
      events that lead to the adhesion and growth of these cells that ultimately result
      in endometriosis, considering the fact that the disease occurs only in certain
      women despite the common occurrence of retrograde menstruation in most women. We
      postulate that, in normal women, the endometrial cells and tissue that arrive in
      the peritoneal cavity during menstruation are effectively removed by macrophages
      that are chemoattracted and become resident tissue macrophages in the peritoneal
      cavity. In contrast, the peritoneal macrophages in women with endometriosis are
      nonadherent and ineffectively scavenged, resulting in the sustained presence and
      growth of the endometrial cells. We also postulate that the peritoneal fluid is
      not a passive reservoir of the factors secreted by cells of the peritoneum, but
      actively promotes endometriosis. The peritoneal fluid is rich in lipoproteins,
      particularly low-density lipoprotein, which generates oxidized lipid components
      in a macrophage-rich inflammatory milieu. The oxidants exacerbate the growth of
      endometriosis by inducing chemoattractants such as MCP-1 and endometrial cell
      growth-promoting activity. We provide evidence for the presence of oxidative
      milieu in the peritoneal cavity of women with endometriosis, the nonscavenging
      properties of macrophages that are nonadherent, and the synergistic interaction
      between macrophages, oxidative stress, and the endometrial cells. For example,
      the peritoneal fluid lipoproteins of subjects with endometriosis have increased
      the propensity to undergo oxidation as compared with plasma lipoproteins, and the
      subjects also have increased titer of autoantibodies to oxidatively modified
      proteins. If the oxidative proinflammatory nature of the peritoneal fluid is an
      important mediator of endometriosis growth, anti-inflammatory agents and
      antioxidants might afford protection against endometriosis.

PMID- 11949948
TI  - The potential role of exposure to environmental toxicants in the pathophysiology
      of endometriosis.
AB  - Humans and animals are exposed daily to a complex mixture of polyhalogenated
      aromatic hydrocarbons (PHAHs). Previous work has shown that exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) is associated with a dose-dependent increase
      in the incidence and severity of endometriosis in the rhesus monkey. Dioxin-like
      chemicals can also exert effects in combination with TCDD via the aryl
      hydrocarbon receptor. Using a rhesus model of chronic TCDD exposure and
      endometriosis, serum concentrations of TCDD and 19 dioxin-like PHAHs were
      quantified 13 years after termination of exposure to TCDD. In additional studies,
      the immune status of TCDD-exposed monkeys was evaluated. For TCDD-exposed and
      unexposed animals, TCDD exposure correlated with an increased serum TCDD
      concentration. Furthermore, TCDD exposure and an elevated serum TCDD
      concentration were associated with increased serum levels of triglycerides,
      1,2,3,6,7,8-hexachlorodibenzofuran (HxCDF), PCB77, and PCB126. Importantly, the
      animals with elevated serum levels of PCB77 and PCB126 and increased total serum
      TCDD equivalents (TEQs) had a high prevalence of endometriosis, and the severity
      of disease correlated with the serum concentration of PCB77. In immune studies,
      TCDD exposure correlated with increased tumor necrosis factor alpha (TNFalpha)
      production by peripheral blood mononuclear cells (PBMC) in response to
      stimulation by T cell mitogen and decreased NK cytolytic activity. Elevated serum
      concentrations of TCDD, 1,2,3,6,7,8-HxCDF, and PCB126 correlated with increased
      numbers of CD3+/CD25- and CD3-/CD25+ leukocytes and enhanced secretion of
      TNFalpha by mitogen-stimulated PBMC. This evidence suggests that TCDD exposure
      and endometriosis in the rhesus monkey may be associated with increased serum
      concentrations of specific coplanar PCB compounds and long-term alterations in
      systemic immunity. Furthermore, the data suggest a potential involvement of an
      increased body burden of PCB compounds in the etiology of endometriosis in the
      rhesus. Recent advances in the detection and assay of individual PHAH congeners
      in biological samples have made it possible to assess total PHAH body burden in
      humans and animals. Future studies are expected to exploit this advance to assess
      the health impact of PHAH body burdens in both exposed individuals and the
      general population. Serum PHAH concentrations and TEQs in TCDD-exposed monkeys
      with endometriosis are similar to or lower than blood levels in the general human
      population; thus, it is important to consider the implications of these findings
      for human health and the prevalence of endometriosis in humans. Additional
      studies are warranted, particularly in human subjects, to explore the potential
      implications of these data.

PMID- 11949949
TI  - Environmental contaminants and dietary factors in endometriosis.
AB  - Endometriosis is an estrogen-dependent disease characterized by the presence of
      endometrial glands and stroma outside the uterine cavity. The etiology of this
      disease remains elusive, but is clearly influenced by genetic, immune, and
      endocrine factors. Exposure to environmental contaminants has recently been added
      to the list of potential factors that contribute to the pathogenesis of
      endometriosis. The objective of this paper is to review the weight of the
      evidence from hospital-based case-control studies and animal experiments for an
      association between exposure to environmental contaminants and endometriosis.

PMID- 11949950
TI  - Endometriosis and infertility: a cause-effect relationship?
AB  - Two major methodological problems that impact clinical research in endometriosis
      are the absence of a low-cost, highly reliable method for diagnosing
      endometriosis and the possibility that endometriosis is actually multiple
      different diseases that we have not yet been able to differentiate. Animal models
      of endometriosis clearly demonstrate that advanced endometriosis causes reduced
      fertility. In humans, endometriosis and infertility are commonly associated.
      However, few data from high-quality clinical trials demonstrate that
      endometriosis causes infertility in humans. Future research should focus on the
      implications of the observation that, in ovarian endometriosis cysts, the
      epithelium is monoclonal. This observation suggests that nonrandom somatic
      mutations cause ovarian endometriosis cysts. If somatic mutations cause ovarian
      endometriosis cysts, it is likely that a small number of genes can be identified
      that play a central role in pathogenesis of this disease.

PMID- 11949951
TI  - The genetic epidemiology of spontaneous endometriosis in the rhesus monkey.
AB  - The etiology of endometriosis is uncertain, but there is increasing evidence that
      it is inherited as a complex genetic trait like diabetes or asthma. In such
      complex traits, multiple gene loci conferring susceptibility to the disease
      interact with each other and the environment to produce the phenotype. The study
      of such interactions in humans can be problematic. Thus, the availability of an
      animal model, which shares many aspects of anatomy and physiology with humans, is
      potentially a valuable tool for investigating the genetic epidemiology of the
      disease. Since endometriosis develops spontaneously in the rhesus monkey (Macaca
      mulatta) and the tissue is morphologically identical to its human counterpart,
      this population provides a unique opportunity to conduct such studies in this
      condition.

PMID- 11949952
TI  - Heritability and molecular genetic studies of endometriosis.
AB  - Endometriosis is well established as a condition showing heritable tendencies.
      Polygenic/multifactorial etiology appears far more likely to be the etiology than
      Mendelian inheritance. The current task is to determine the number and location
      of genes responsible for endometriosis. This paper shall review the basis for
      concluding that endometriosis is a genetic disorder of polygenic/multifactorial
      inheritance and outline selected strategies for identifying the number and
      location of causative genes. It shall also illustrate our approach to testing the
      hypothesis that endometriosis bears similarity to neoplasia and, hence, is a
      multistep phenomenon of clonal origin.

PMID- 11949953
TI  - The molecular basis for implantation failure in endometriosis: on the road to
      discovery.
AB  - Endometriosis is a benign gynecologic disorder associated with pelvic pain and
      infertility, with the latter being due, in part, to failure of embryonic
      implantation in the maternal endometrium. Adequacy of the endometrium for
      fertility has been classically investigated by histologic evaluation of a mid
      late luteal phase biopsy and, historically, normal histology has been reassuring.
      However, recent studies demonstrate histologically normal, but biochemically
      abnormal, endometrium during the window of implantation in some women with
      endometriosis. In the pregenomic era, a "one-by-one" approach has been adopted to
      investigate proteins and genes expressed in the window of implantation, and
      several genes or gene products have been found to be aberrantly expressed in
      endometrium of women with endometriosis either during the implantation window or
      at other times of the cycle. Some of these are related to failure of
      implantation, while others likely contribute to the establishment and growth of
      endometriotic lesions. The time has come for a genome-wide approach to evaluate
      uterine endometrium for embryonic implantation. Knowing the biochemical
      mechanisms underlying normal implantation and the abnormalities in endometriosis
      will facilitate development of new diagnostic criteria beyond histologic
      evaluation and will permit identification and validation of molecular targets for
      future drug discovery. This monograph reviews (a) some of the evidence of
      compromised fertility in women with endometriosis and treatments targeted to
      improve their fertility; (b) the concept of the window of implantation; (c)
      genes/gene products aberrantly expressed in endometrium during the window of
      implantation or other times of the cycle in women with endometriosis; and (d) the
      use of microarray technology to investigate endometrial gene expression in human
      endometrial stromal cells and preliminary data resulting from a collaborative
      consortium effort of a genome-wide investigation of gene expression in the window
      of implantation of women with versus without endometriosis.

PMID- 11949954
TI  - Implantation defects in infertile women with endometriosis.
AB  - The endometrium undergoes characteristic histologic changes during the menstrual
      cycle as it prepares for embryo implantation. Historic and current data suggest
      the presence of a defined period of maximal uterine receptivity during the mid
      secretory phase occurring between days 7 and 10 postovulation. In recent years,
      we and others have sought to define biochemical markers of receptivity that might
      be used to better understand this time of endometrial differentiation. Based on
      the work with cell adhesion molecules, we have discovered three different
      integrins that are only coexpressed during this time in the cycle when embryos
      will successfully implant. By studying the regulation of one of these, the
      alpha(v)beta3 integrin, and its extracellular matrix ligand, osteopontin (OPN),
      we have defined two separate regulatory pathways that may regulate endometrial
      receptivity. While alpha(v)beta3 expression appears to be stimulated by EGF or
      heparin-binding EGF, osteopontin is stimulated by progesterone. We now believe
      the former pathway is a paracrine-mediated signal, while the latter is a direct
      effect of progesterone on the estrogen-primed endometrial epithelium. In women
      with endometriosis, it appears that alpha(v)beta3 expression is reduced, while
      OPN expression is unaffected. Interestingly, binding of OPN to the surface
      epithelium appears quite limited when alpha(v)beta3 expression is lacking. Such
      evidence continues to reinforce the notion that endometrium from some women with
      endometriosis is dysfunctional and may account for the reduction in cycle
      fecundity noted in this group of patients.

PMID- 11949955
TI  - Role of endometriosis in cancer and tumor development.
AB  - Endometriosis, like cancer, is characterized by cell invasion and unrestrained
      growth. Furthermore, endometriosis and cancer are similar in other aspects, such
      as the development of new blood vessels and a decrease in the number of cells
      undergoing apoptosis. In spite of these similarities, endometriosis is not
      considered a malignant disorder. The possibility that endometriosis could,
      however, transform and become cancer has been debated in the literature since
      1925. Mutations in the genes that encode for metabolic and detoxification
      enzymes, such as GALT and GSTM, have been implicated in the pathogenesis of
      endometriosis and in the progression to carcinoma of the ovary. PTEN, a tumor
      suppressor commonly mutated (50%) in endometrial carcinoma, is found mutated in
      endometrioid carcinoma of the ovary, but not in other forms of ovarian cancer. A
      recent study has shown that somatic mutations in the PTEN gene were identified in
      20% of endometrioid carcinomas and 20.6% of solitary endometrial cysts,
      suggesting that inactivation of the PTEN tumor suppressor gene is an early event
      in the development of ovarian endometrioid carcinoma. In addition to cancerous
      transformation at the site of endometriosis, there is recent evidence to indicate
      that having endometriosis itself may increase a woman's risk of developing non
      Hodgkin's lymphoma, malignant melanoma, and breast cancer.

PMID- 11949956
TI  - An in vitro model to study the pathogenesis of the early endometriosis lesion.
AB  - OBJECTIVE: To determine if whole fragments of endometrium can adhere to
      peritoneum with intact mesothelium. DESIGN: Tissue culture and
      immunohistochemical study. SETTING: University Medical Center. PATIENTS:
      Reproductive-age women undergoing surgery for benign conditions. INTERVENTIONS:
      Whole explants of human peritoneum from the anterior abdominal wall and the
      posterior surface of the uterus were cultured with whole fragments of
      mechanically dispersed endometrium. MAIN OUTCOME MEASURES: Adhesion of
      endometrial fragments to the surface of the peritoneum was evaluated. Adherent
      fragments of endometrium were identified using the dissecting microscope and by
      performing serial sections of the peritoneum explants for light and confocal
      laser-scanning microscopy. Immunohistochemical staining of the mesothelium with
      antibodies to cytokeratin and vimentin was used to ensure an intact layer of
      mesothelium beneath the endometrial implants. Transmission electron microscopy
      was also used to evaluate the adhesion of endometrium to the mesothelium.
      RESULTS: Endometrium was identified attached to the surface of the peritoneum.
      After 18-24 hours of culture, the majority of implants did not have identifiable
      mesothelium beneath them, but most had intact mesothelium running up to the point
      of attachment. Approximately 10% of the endometrial implants had intact
      mesothelium at the site of attachment. After 1 hour of culture, both endometrial
      stromal and epithelial cells were attached to intact mesothelium in nearly all
      cases. Early transmesothelial invasion involves endometrial stromal cells.
      CONCLUSIONS: Endometrial stromal and epithelial cells can attach to the intact
      mesothelial surface of the peritoneum. Endometrial stromal cell invasion through
      the mesothelium occurs in less than 18-24 hours.

PMID- 11949957
TI  - A modified baboon model for endometriosis.
AB  - Endometriosis is one of the most common causes of infertility and chronic pelvic
      pain and affects 1 in 10 women in the reproductive-age group. Although existence
      of this disease has been known for over 100 years, our current knowledge of its
      pathogenesis, the pathophysiology of related infertility, and its spontaneous
      evolution is limited. Several reasons contribute to our lack of knowledge, the
      most critical being the difficulty in carrying out objective long-term studies in
      women. Thus, we and others have developed the baboon as an appropriate nonhuman
      primate to study the etiology of this disease. We suggested that endometriosis
      develops in two distinct phases. Phase I is invasive and dependent on ovarian
      steroids. Phase II, which is the active phase of the disease, is characterized by
      endogenous estrogen biosynthesis. Following inoculation with menstrual
      endometrial tissues in two consecutive menstrual cycles, baboons develop lesions
      that are similar to those seen in humans. Laparoscopy at 1, 4, and 10 months
      revealed a preponderance of red raised nodules at the first month, while both red
      lesions and reddish-blue proliferative endometriotic lesions were evident at 4
      and 10 months. The presence of glandular tissue and stromal fibroblasts in these
      lesions was confirmed by histology. Lesions obtained at 1 and 4 months expressed
      estrogen receptor beta (ERbeta), matrix metalloproteinase-7 (MMP-7), and vascular
      endothelial growth factor (VEGF) predominantly. However, aromatase expression was
      only readily evident at 10 months, although some lesions obtained at 4 months
      expressed low levels of aromatase. Therefore, our preliminary data suggest that
      endometriosis can be artificially induced in baboons, and the role of exogenous
      and endogenous estradiol in proliferation, angiogenesis, and immune modulations
      can now be evaluated in a potentially systemic manner.

PMID- 11949958
TI  - Using rats as a research model for the study of endometriosis.
AB  - Although there are disadvantages of extrapolating data across species, the rat
      model may be used to study events involved in the pathogenesis and
      pathophysiologies of endometriosis or novel therapeutic approaches for this
      disorder that are not accessible in humans. Rat endometriotic tissues are similar
      to human lesions in vivo, and rat endometriotic tissues and cells perform in a
      similar manner as human endometriotic tissues and cells in organ explant culture
      and isolated cell culture. The rat model permits studies of mechanisms and
      regulators in a controlled manner free from confounding influences such as
      individual patient variation and environmental influences. The primary method
      used for induction of endometriosis in rats has been autotransplantation of
      uterine squares (implants) into the peritoneal cavity. Beyond mere growth of
      endometrium in ectopic locations, rats with endometriosis display similar
      symptoms, including a reduction in fertility and fecundity, and the endometriotic
      implants react similarly to therapeutics as those of humans with the disease.
      Similar alterations in gene expression and protein production have been observed
      in endometriotic tissues from rats and humans that may, in part, be causative
      agents involved in the pathogenesis or pathophysiologies of endometriosis.

PMID- 11949959
TI  - Experimental endometriosis: the nude mouse as a xenographic host.
AB  - Endometriosis is a complex disease that can develop as a consequence of
      retrograde menstruation, occurring in association with the cyclic loss of
      endometrial tissue in primates and humans. In addition, progression of disease
      parallels a woman's exposure to ovarian steroids, rarely occurring prior to
      menarche and generally resolving following menopause. Because of the cost of
      developing primate models to study endometriosis, numerous small animal models
      have been established to approach various elements related to the pathophysiology
      of this disease. Our laboratory has developed an experimental endometriosis model
      using nude mice as a xenographic host for human tissues. Our goal is to approach
      the basic cellular mechanisms of estrogen and progesterone action that link these
      hormones to the development or prevention of endometriosis. In our initial
      studies, we have sought to understand steroid-associated regulation of matrix
      metalloproteinases (MMPs) with regard to the development of experimental
      endometriosis. Using both short-term organ cultures and nude mice as xenographic
      hosts of human tissue, we have demonstrated a critical role of progesterone and
      progesterone-associated cytokines in preventing the initial establishment of
      experimental disease. Women with endometriosis appear to lack normal endometrial
      responsiveness to progesterone, resulting in altered expression of several MMPs
      and an enhanced ability of these tissues to establish ectopic lesions in nude
      mice. Developing a better understanding of the impairments in the normal
      endometrial physiology of women with endometriosis should aid in the development
      of better treatment or diagnostic strategies.

PMID- 11949960
TI  - Conventional medical therapies for endometriosis.
AB  - Endometriosis is a common gynecologic disorder that affects approximately 14% of
      all women and 30% to 50% of infertile women. Since the most common symptoms of
      endometriosis--progressive dysmenorrhea, dyspareunia, chronic pelvic pain, and
      infertility--are also symptoms of multiple disorders, a diagnosis of
      endometriosis can be elusive and confirmed only by visualization, that is,
      laparoscopy. Endometriosis is often treated surgically upon diagnosis; however,
      the rate of recurrence is high, suggesting that a combination of therapeutic
      approaches might provide better outcomes than any one option alone. The most
      widely utilized hormonal treatments for endometriosis are GnRH agonists and oral
      contraceptives; agents indicated by the Food and Drug Administration include GnRH
      agonists and the androgen, danazol. The majority of evidence in support of
      medical therapy for endometriosis is largely observational, with the exception of
      studies of GnRH agonists, danazol, and a few progestins. Conventional treatment
      approaches for the medical management of endometriosis focus on suspected
      endometriosis, following a diagnosis of endometriosis, following surgical
      treatment of endometriosis, long-term management, and retreatment. Although major
      advances have been made in the treatment of endometriosis in recent decades, lack
      of randomized clinical trials evaluating the use of agents such as oral
      contraceptives alone or as add-back therapy for GnRH agonists, or those that
      examine combined medical and surgical treatments, has hampered the ability of
      physicians to provide the broadest range of medical therapies for this disorder.
      Future trials addressing these issues are warranted.

PMID- 11949961
TI  - Research aspects of endometriosis surgery.
AB  - This paper asks various questions regarding endometriosis surgery. These address
      the research issues of the necessity of treatment, surgical technique,
      terminology, the definition of the rectovaginal septum, standards for research,
      and the impact of RBRVS/RDG.

PMID- 11949962
TI  - The treatment of endometriosis: a review of the evidence.
AB  - The treatment of endometriosis focuses upon amelioration of two symptoms: pain
      and infertility. The treatment of endometriosis-associated pain has been well
      studied and all major medical therapies appear to be superior to placebo. In
      addition, none seems to be drastically better than another. Surgical therapy also
      appears to be efficacious, albeit with a relatively high rate of recurrence of
      symptoms following conservative surgical intervention. There are no trials
      comparing the relative value of medical versus surgical therapy. Combination
      surgery/medical therapy has several high-quality trials for evaluation, but its
      value remains unclear. The treatment of endometriosis-associated infertility
      presents a different picture: medical therapy has not been shown to be of any
      value and may prove detrimental to fertility. Surgical treatment does improve
      fertility, probably for all stages of disease. Assisted reproduction also seems
      to be efficacious, with both controlled ovarian hyperstimulation and intrauterine
      insemination as well as in vitro fertilization shown to be of benefit. Finally,
      the combination of in vitro fertilization and either medical or surgical therapy
      may be beneficial with advanced endometriosis, but further study is required.

PMID- 11949963
TI  - Progesterone-mediated endometrial maturation limits matrix metalloproteinase
      (MMP) expression in an inflammatory-like environment: a regulatory system altered
      in endometriosis.
AB  - The human endometrium exhibits regular cycles of growth, differentiation, and
      breakdown in response to changing levels of ovarian steroids. Following the
      tissue loss and repair processes of menstruation, rising levels of estradiol
      initiate a development-like process leading to a complete restructuring of the
      endometrial surface. In contrast, while under the predominate influence of
      progesterone, proliferation declines as cell-specific differentiation prepares
      the endometrium for pregnancy over a 5- to 6-day period. In the absence of
      nidation, steroid support is lost; the endometrial surface begins a complex
      process of tissue breakdown and bleeding, producing a viscous mixture of cellular
      debris within a bloody menstrual effluent. Although most of the menstrual fluid
      exits the body, reflux of some material occurs in most women, providing a poorly
      understood opportunity for ectopic endometrial growth and establishment of the
      disease endometriosis. The cyclic restructuring of the endometrium requires
      numerous matrix metalloproteinases (MMPs) that mediate normal and pathological
      tissue turnover throughout the reproductive tract. The expression of multiple
      MMPs facilitates degradation of extracellular matrix during growth-related
      remodeling as well as tissue breakdown at the time of menstruation. However,
      these enzymes are absent during the early and mid-secretory phase and the
      suppression of endometrial MMPs remains important to maintaining the integrity of
      the endometrium during the highly invasive events required to establish a normal
      hemochorial placenta. Several research groups have suggested that steroid
      mediated expression and action of MMPs during the menstrual cycle may provide a
      key mechanistic link between endometrial turnover and the invasive processes
      necessary for establishment of endometriosis.

PMID- 11949964
TI  - Selective progesterone receptor modulators (SPRMs): a novel therapeutic concept
      in endometriosis.
AB  - Endometriosis, the presence of endometrial tissue outside the uterus, is a
      progressive, estrogen-dependent disease and occurs nearly exclusively in
      menstruating women of reproductive age. Pain syndrome, however, represents the
      major clinical problem of this disease, manifested as dysmenorrhea, pelvic pain,
      lower abdominal pain, and dyspareunia. The manifestation of the disease, that is,
      the pain syndrome, rather than the disease itself currently represents the major
      indication for both the medical and surgical therapies of endometriosis. The
      major drawbacks of current medical therapies of endometriosis are sometimes
      severe side effects. In this review, selective progesterone receptor modulators
      (SPRMs, mesoprogestins) as a potential therapeutic concept in endometriosis are
      discussed. Due to endometrial selectivity and favorable pharmacological profile,
      SPRMs may have advantages over the current medical treatments of this disease.
      Other emerging therapeutic approaches for this disease are also mentioned.

PMID- 11949965
TI  - Mechanisms of action of estrogen and progesterone.
AB  - Estrogen and progesterone are steroid hormones that play a pivotal role in the
      regulation of mammalian reproduction. One primary action of these hormones is to
      regulate the development and function of the uterus. These hormones act by
      regulating the transcription of specific genes in the uterus. The actions of
      these hormones are mediated by their specific hormone receptors. These receptors
      are nuclear transcription factors, whose transcriptional regulatory activity is
      mediated by the binding of the specific steroid to these molecules. Once these
      receptors bind hormone, they can bind to specific cis-acting sequences in the
      promoter region of responsive genes and regulate transcription of these genes. In
      the regulation of transcription, these receptors interact with specific cofactors
      to activate the transcriptional machinery. A second gene family, the Steroid
      Receptor Coactivator (SRC) family, has been identified that serves to modulate
      the transcriptional activity of the hormone receptors. To date, three members of
      the SRC family have been identified. During the last decade, gene targeting
      technology has been used to identify the role of these receptors in the
      regulation of reproduction and uterine biology.

PMID- 11949966
TI  - Premenstrual and menstrual changes in the macaque and human endometrium:
      relevance to endometriosis.
AB  - According to current theory, endometriosis is initiated during retrograde
      menstruation when menstrual fragments flow out of the fimbriated end of the
      fallopian tubes and become established on the ovarian surface or other sites in
      the peritoneal cavity. In recent years, new data have accumulated on the
      properties of menstruating tissue itself, and several laboratories agree that
      this tissue is rich in matrix metalloproteinases (MMPs) that may facilitate
      endometriotic implantation. Recently, we found that vascular endothelial growth
      factor (VEGF) and its receptor VEGFR-2 (KDR) were dramatically upregulated in the
      stromal cells of the superficial endometrial zones by progesterone (P) withdrawal
      during the premenstrual phase. A unique role of VEGF at this stage of the cycle
      may be to stimulate MMP expression in stromal cells because VEGF, KDR, and MMPs
      were all coordinately induced in these cells in the superficial zone of the
      primate endometrium by P withdrawal. The rich content of MMPs and VEGF in the
      menstrual fragments could facilitate attachment and angiogenesis of menstrual
      fragments in ectopic sites. In addition, a variety of chemokines, cytokines, and
      cellular regulators are induced by P withdrawal in the premenstrual human
      endometrium. These include NFKB, prostaglandins, interleukin-8 (IL-8),
      cyclooxygenase-2 (COX-2), and monocyte chemotactic peptide-1 (MCP-1), among
      others. The perivascular expression of several of these factors may facilitate
      the rapid invasion of leukocytes into the endometrium, especially in the
      superficial zones. Consequently, menstrual fragments may be rich in IL-8 and MCP
      1, both of which would add to the angiogenic potential of such fragments in
      ectopic sites. In sum, menstrual tissue is rich in VEGF, KDR, MMPs, leukocytes,
      chemokines, cytokines, and prostaglandins, all factors that may facilitate
      attachment and angiogenesis when menstrual fragments exit from the tubes and
      implant on pelvic sites. Additional research on these and other factors in
      premenstrual and menstrual endometrium may deepen our understanding of both the
      establishment and progression of this debilitating disease.

PMID- 11949967
TI  - Estrogen production and metabolism in endometriosis.
AB  - Aromatase activity is absent in normal endometrium. In contrast, aromatase is
      expressed aberrantly in endometriosis, which gives rise to strikingly high levels
      of aromatase activity in this tissue. Both aromatase expression and activity are
      stimulated by PGE2. This results in local production of estrogen, which induces
      PGE2 formation and establishes a positive feedback cycle. Another abnormality in
      endometriosis, that is, deficient 17beta-HSD type 2 expression, impairs the
      inactivation of estradiol to estrone. These molecular aberrations collectively
      favor accumulation of increasing quantities of estradiol and PGE2 in
      endometriosis. The clinical relevance of these findings was exemplified by the
      successful treatment of an unusually aggressive case of postmenopausal
      endometriosis using an aromatase inhibitor.

PMID- 11949968
TI  - Angiogenic factors in endometriosis.
AB  - Similar to tumor metastases, endometriotic implants require neovascularization to
      establish, grow, and invade. The peritoneal environment is ideally suited to
      provide a proangiogenic milieu. Nevertheless, endometriotic lesions are found
      only in a minority of reproductive-age women (approximately 10%) with retrograde
      menstruation. In this paper, we review the major cytokines, growth factors,
      steroid hormones, and eicosanoids responsible for angiogenesis in endometriosis.
      We postulate that interference with angiogenic principles expressed in the
      peritoneum may constitute novel therapeutic opportunities for the prevention,
      amelioration, or treatment of pelvic endometriosis.

PMID- 11949969
TI  - The effect of dimension and vocabulary age on rapid picture naming in children.
AB  - This investigation involved measures of the reaction times of normally developing
      children who were asked to name a series of centrally presented picture stimuli
      of varying vocabulary age and dimension. Results of the ANOVA on reaction times
      indicated a significant main effect of vocabulary level and an interaction of
      Dimension x Vocabulary level for the normally developing children. Post-hoc tests
      showed significant differences between two- and three-dimensional pictures for
      higher-level vocabulary items, but not for lower-level vocabulary items. This
      finding indicates that central operations involved in picture naming are
      influenced differentially by the physical characteristics of the stimulus items.
      The finding that two-dimensional higher-level vocabulary items were associated
      with significantly longer reaction times than the three-dimensional higher-level
      vocabulary suggests that dimensionality may be a critical feature for rapid
      lexical access for higher-level picture vocabulary. Clinically, the employment of
      three-dimensional forms may facilitate access to stored visual object memory for
      advanced levels of picture vocabulary. LEARNING OUTCOMES: As a result of this
      activity, participants will be able to (1) identify the various visual and verbal
      processes involved in the naming of pictures; and (2) understand the influence of
      physical characteristics of pictures on reaction time in rapid naming tasks.

PMID- 11949970
TI  - Intonation in partner accommodation for aphasia: a descriptive single case study.
AB  - Previous research has suggested that speaking partners adjust their intonation
      when conversing with people who are ill or elderly. In the descriptive case study
      presented in this paper we ask, what adjustments in intonation might be made by
      the communication partner of an aphasic speaker? A sociolinguistic, semantic
      analysis of intonation was used to describe the intonation pattern used by the
      neighbor of an aphasic speaker, during a 15-min natural interaction with the
      aphasic speaker, his wife, and the first author. The neighbor was found to make
      more use of two dimensions of intonation that reflected differences in her
      relationship to the information conveyed, when addressing the aphasic speaker in
      contrast to when addressing his wife. Firstly, she made proportionally more use
      of pitch movements associated with referring to shared information, and secondly,
      she made more use of marked tones (rising-falling, and rising tones). We discuss
      whether the observed differences may represent an accommodation to speaking to a
      person with aphasia. LEARNING OUTCOMES: The reader will be able: (1) to recognize
      the role of intonation in discourse as a resource for the exchange of
      interpersonal meaning, and (2) to identify when speakers are using intonation as
      part of their speech accommodation for aphasia.

PMID- 11949971
TI  - The integrity of the syllable in developmental apraxia of speech.
AB  - Three children with developmental apraxia of speech (DAS) identified the number
      of syllables in words, judged intrasyllabic sound positions, and constructed
      syllable shapes within monosyllabic frames. Results suggest that DAS children
      demonstrate an apparent breakdown in the ability to perceive "syllableness" and
      to access and compare syllable representations with regard to position and
      structure. Based on these findings, DAS is viewed as a disorder characterized by
      an impoverished phonological representation system. LEARNING OUTCOMES: On the
      basis of this article, the reader will be able to (1) describe the deficits in
      syllabic perception demonstrated by some participants with DAS; (2) examine the
      utility of metalinguistic tasks in the differential diagnosis of DAS; and (3)
      evaluate the findings with respect to competing theoretical perspectives on DAS.

PMID- 11949972
TI  - Preservation of second formant transitions during simultaneous communication: a
      locus equation perspective.
AB  - This study investigated the preservation of second formant transition acoustic
      cues to intelligibility in speech produced during simultaneous communication (SC)
      from a locus equation perspective. Twelve normal hearing, experienced sign
      language users were recorded under SC and speech alone (SA) conditions speaking a
      set of sentences containing monosyllabic words designed for measurement of second
      formant frequencies in consonant-vowel-consonant (CVC) syllables. Linear
      regression fits made to coordinates representing second formant transition onset
      and offset frequencies following stop consonant release of CVC syllables (locus
      equations) were used to examine place of articulation cues in both SA and SC
      conditions. Although results indicated longer sentence durations for SC than SA,
      locus equation slopes and intercepts obtained from speech produced during SC were
      virtually identical to those obtained during SA, indicating no degradation of
      stop consonant acoustic cues during SC. This conclusion is consistent with
      previous research indicating that temporal alterations produced by SC do not
      involve violations of other rules of spoken English. EDUCATIONAL OBJECTIVES: As a
      result of this activity, the participant will be able to (1) describe SC; (2)
      explain the role of SC in communication with children who are deaf; (3) describe
      second formant transitions in English speech; and (4) identify second formant
      transition patterns in speech produced during SC.

PMID- 11949974
TI  - Hippocrates redux.

PMID- 11949973
TI  - The effect of temporal manipulation on the perception of disfluencies as normal
      or stuttering.
AB  - The purpose of this investigation was to study the effect of temporal features
      within repetition of speech segments on the perception of stuttering. Past
      research has provided evidence that certain temporal aspects of repetitions
      produced by people who stutter tend to be shorter than those produced by normally
      fluent speakers. The effect of these temporal factors on the perception of the
      disfluency as "stuttering" or "normal" has not yet been studied. Conversational
      speech of five children who stutter was recorded. Two short utterances. one
      containing part-word repetition (PWR) and one containing whole-word repetition
      (WWR), were identified in the speech of each child and then manipulated by the
      CSL and CSpeech computer softwares. Two selected elements within repetitions,
      namely the vowel of the repeated unit and the interval between the repeated units
      (e.g., but-but), were lengthened to simulate normal disfluency. Results indicated
      that both factors (interval duration and vowel duration) moderately affected
      listeners' perception. In general, repetitions with short vowel and interval
      durations were judged as more representative of stuttering, whereas repetitions
      with longer vowel and interval duration were judged as more representative of
      normal speech. LEARNING OUTCOMES: As a result of this activity, the reader will
      learn about (1) various factors that influence the perception of disfluent
      segments as stuttering, (2) the special effect of duration of specific elements
      within repetitions on the perception of disfluency as stuttering, and (3) the
      possible implications of the new information for therapeutic considerations.

PMID- 11949975
TI  - Vituperation in Edmonton.

PMID- 11949976
TI  - Conclusions from McMaster's peace conference "ludicrous and bizarre".

PMID- 11949977
TI  - Short and sweet.

PMID- 11949978
TI  - Why are Quebec's doctors leaving?

PMID- 11949979
TI  - Canker sore remedies: baking soda.

PMID- 11949980
TI  - Adverse drug reaction reporting controversy.

PMID- 11949981
TI  - Clinicians' role in responding to bullying.

PMID- 11949982
TI  - Air travel and venous thromboembolism--the jury is still out.

PMID- 11949983
TI  - Clarifying chiropractic manipulation risks.

PMID- 11949984
TI  - Current and former marijuana use: preliminary findings of a longitudinal study of
      effects on IQ in young adults.
AB  - BACKGROUND: Assessing marijuana's impact on intelligence quotient (IQ) has been
      hampered by a lack of evaluation of subjects before they begin to use this
      substance. Using data from a group of young people whom we have been following
      since birth, we examined IQ scores before, during and after cessation of regular
      marijuana use to determine any impact of the drug on this measure of cognitive
      function. METHODS: We determined marijuana use for seventy 17- to 20-year-olds
      through self-reporting and urinalysis. IQ difference scores were calculated by
      subtracting each person's IQ score at 9-12 years (before initiation of drug use)
      from his or her score at 17-20 years. We then compared the difference in IQ
      scores of current heavy users (at least 5 joints per week), current light users
      (less than 5 joints per week), former users (who had not smoked regularly for at
      least 3 months) and non-users (who never smoked more than once per week and no
      smoking in the past two weeks). RESULTS: Current marijuana use was significantly
      correlated (p < 0.05) in a dose-related fashion with a decline in IQ over the
      ages studied. The comparison of the IQ difference scores showed an average
      decrease of 4.1 points in current heavy users (p < 0.05) compared to gains in IQ
      points for light current users (5.8), former users (3.5) and non-users (2.6).
      INTERPRETATION: Current marijuana use had a negative effect on global IQ score
      only in subjects who smoked 5 or more joints per week. A negative effect was not
      observed among subjects who had previously been heavy users but were no longer
      using the substance. We conclude that marijuana does not have a long-term
      negative impact on global intelligence. Whether the absence of a residual
      marijuana effect would also be evident in more specific cognitive domains such as
      memory and attention remains to be ascertained.

PMID- 11949985
TI  - Risk factors for elevated HIV incidence rates among female injection drug users
      in Vancouver.
AB  - BACKGROUND: In 1997, we found a higher prevalence of HIV among female than among
      male injection drug users in Vancouver. Factors associated with HIV incidence
      among women in this setting were unknown. In the present study, we sought to
      compare HIV incidence rates among male and female injection drug users in
      Vancouver and to compare factors associated with HIV seroconversion. METHODS:
      This analysis was based on 939 participants recruited between May 1996 and
      December 2000 who were seronegative at enrolment with at least one follow-up
      visit completed, and who were studied prospectively until March 2001. Incidence
      rates were calculated using the Kaplan-Meier method. The Cox proportional hazards
      regression model was used to identify independent predictors of time to HIV
      seroconversion. RESULTS: As of March 2001, seroconversion had occurred in 110 of
      939 participants (64 men, 46 women), yielding a cumulative incidence rate of HIV
      at 48 months of 13.4% (95% confidence interval [CI] 11.0%-15.8%). Incidence was
      higher among women than among men (16.6% v. 11.7%, p = 0.074). Multivariate
      analysis of the female participants' practices revealed injecting cocaine once or
      more per day compared with injecting less than once per day (adjusted relative
      risk [RR] 2.6, 95% CI 1.4-4.8), requiring help injecting compared with not
      requiring such assistance (adjusted RR 2.1, 95% CI 1.1-3.8), having unsafe sex
      with a regular partner compared with not having unsafe sex with a regular partner
      (adjusted RR 2.9, 95% CI 0.9-9.5) and having an HIV-positive sex partner compared
      with not having an HIV-positive sex partner (adjusted RR 2.7, 95% CI 1.0-7.7) to
      be independent predictors of time to HIV seroconversion. Among male participants,
      injecting cocaine once or more per day compared with injecting less than once per
      day (adjusted RR 3.3, 95% CI 1.9-5.6), self-reporting identification as an
      Aboriginal compared with not self-reporting identification as an Aboriginal
      (adjusted RR 2.5, 95% CI 1.4-4.2) and borrowing needles compared with not
      borrowing needles (adjusted RR 2.0, 95% CI 1.1-3.4) were independent predictors
      of HIV infection. INTERPRETATION: HIV incidence rates among female injection drug
      users in Vancouver are about 40% higher than those of male injection drug users.
      Different risk factors for seroconversion for women as opposed to men suggest
      that sex-specific prevention initiatives are urgently required.

PMID- 11949986
TI  - Failure to prevent perinatal HIV infection.

PMID- 11949987
TI  - Slowing the progression of chronic renal insufficiency.

PMID- 11949988
TI  - HIV incidence among injection drug users in Vancouver.

PMID- 11949989
TI  - Aiming for zero: preventing mother-to-child transmission of HIV.

PMID- 11949990
TI  - Clinical nutrition: 6. Management of nutritional problems of patients with
      Crohn's disease.

PMID- 11949991
TI  - New advances in the management of acute coronary syndromes: 4. Low-molecular
      weight heparins.

PMID- 11949992
TI  - Prevention of group B streptococcal infection in newborns: recommendation
      statement from the Canadian Task Force on Preventive Health Care.

PMID- 11949993
TI  - Oral contraceptives and myocardial infarction.

PMID- 11949994
TI  - Droperidol: cardiovascular toxicity and deaths.

PMID- 11949995
TI  - Porcelain gallbladder.

PMID- 11949996
TI  - No ban on reuse of single-use medical devices imminent.

PMID- 11949997
TI  - "A completely preventable death".

PMID- 11949998
TI  - Push for consumer drug ads gets cool reception in Europe.

PMID- 11949999
TI  - Number of injury-related hospitalizations drops.

PMID- 11950001
TI  - NSAID toxicity: where are we and how do we go forward?

PMID- 11950000
TI  - Infliximab: additional safety data from an open label study.

PMID- 11950002
TI  - Scoring methods.

PMID- 11950003
TI  - Shift happens: complementary and alternative medicine for rheumatologists.

PMID- 11950004
TI  - Immunosuppressant effect of IDS 30, a stinging nettle leaf extract, on myeloid
      dendritic cells in vitro.
AB  - OBJECTIVE: Dendritic cells are important antigen presenting cells that play a
      role in the initiation of rheumatoid arthritis (RA). The stinging nettle leaf
      extract IDS 30 (Hox alpha) has been recommended for adjuvant therapy of rheumatic
      diseases. We investigated the immunomodulating effect of IDS 30 extract on the
      maturation of hematopoietic dendritic cells. METHODS: Human dendritic cells were
      generated from peripheral blood mononuclear cells cultured in granulocyte
      macrophage-colony stimulating factor and interleukin 4 (IL-4). Dendritic cell
      maturation was induced by keyhole limped hemocyanin (KLH). Dendritic cell
      phenotype was characterized by flow cytometric analysis; dendritic cell cytokine
      production was measured by ELISA. The ability of dendritic cells to activate
      naive autologous T cells was evaluated by mixed leukocyte reaction. RESULTS: IDS
      30 prevented the maturation of dendritic cells, but did not affect their
      viability. IDS 30 reduced the expression of CD83 and CD86. It increased the
      expression of chemokine receptor 5 and CD36 in a dose dependent manner. The
      secretion of tumor necrosis factor-alpha was reduced. Application of IDS 30 to
      dendritic cells in culture caused a high endocytosis of dextran and a low
      capacity to stimulate T cell proliferation. CONCLUSION: Our in vitro results
      showed the suppressive effect of IDS 30 on the maturation of human myeloid
      dendritic cells, leading to reduced induction of primary T cell responses. This
      may contribute to the therapeutic effect of IDS 30 on T cell mediated
      inflammatory diseases like RA.

PMID- 11950005
TI  - Open label study to assess infliximab safety and timing of onset of clinical
      benefit among patients with rheumatoid arthritis.
AB  - OBJECTIVE: To assess the timing of onset of clinical benefit following the
      initial infusion of infliximab and to obtain additional safety experience of
      infliximab when given in an office setting to patients with rheumatoid arthritis
      (RA). In addition, the safety of reducing the infusion time from 2 hours to 1
      hour was evaluated. METHODS: Patients (n = 553) with active RA despite receiving
      methotrexate (MTX) were treated with infliximab 3 mg/kg given over 2 h at
      baseline (Week 0), and Weeks 2, 6, and 14 in this multicenter open-label trial.
      Patients continued to receive a stable dose of MTX (> or = 7.5 mg/wk). At
      selected sites, patients tolerating the first 4 infusions were eligible to
      receive 2 additional infusions at twice the usual infusion rate (given over 1 h).
      Patients returned for efficacy assessments at 48 h following the initial infusion
      and several times throughout study participation. RESULTS: By 48 h following the
      first infusion, significant (p < 0.001) improvements were observed in duration of
      morning stiffness (34% mean improvement), physician's global disease assessment
      scores (30%), patient's global disease assessment scores (25%), and patient's
      pain assessment scores (30%). By Week 16, 52 to 63% mean improvements in these
      efficacy variables were observed (p < 0.001), the significant improvement was
      maintained through the end of study participation in the subset of patients who
      received the additional 1 h infliximab infusions. Through 16 weeks, 10% (54/553)
      of patients reported an adverse event associated with at least 1 of the 4
      infusion procedures; the majority were mild and transient in nature. In the
      subset of 197 patients who received 2 additional infusions over 1 h, no increase
      in the frequency or severity of infusion-related adverse events was observed
      compared to the 2 h infusion. CONCLUSION: Infliximab administered to patients
      with RA in an outpatient setting resulted in significant clinical improvement
      within 48 h that was sustained with additional infusions. Approximately 10% of
      patients experienced an infusion reaction, highlighting the need for direct
      supervision over patient treatment. Patients who tolerated infliximab infusions
      given over 2 h also tolerated a 1 h infusion.

PMID- 11950006
TI  - Randomized double blind trial of an extract from the pentacyclic alkaloid
      chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate safety and clinical efficacy of a plant extract from the
      pentacyclic chemotype of Uncaria tomentosa (UT) in patients with active
      rheumatoid arthritis (RA). METHODS: Forty patients undergoing sulfasalazine or
      hydroxychloroquine treatment were enrolled in a randomized 52 week, 2 phase
      study. During the first phase (24 weeks, double blind, placebo controlled),
      patients were treated with UT extract or placebo. In the second phase (28 weeks)
      all patients received the plant extract. RESULTS: Twenty-four weeks of treatment
      with the UT extract resulted in a reduction of the number of painful joints
      compared to placebo (by 53.2% vs 24.1%; p = 0.044). Patients receiving the UT
      extract only during the second phase experienced a reduction in the number of
      painful (p = 0.003) and swollen joints (p = 0.007) and the Ritchie Index (p =
      0.004) compared to the values after 24 weeks of placebo. Only minor side effects
      were observed. CONCLUSION: This small preliminary study demonstrates relative
      safety and modest benefit to the tender joint count of a highly purified extract
      from the pentacyclic chemotype of UT in patients with active RA taking
      sulfasalazine or hydroxychloroquine.

PMID- 11950007
TI  - Comparison of the Rau method and the Larsen method in the evaluation of
      radiographic progression in early rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the usefulness of the radiographic scoring method
      proposed by Rau, et al for evaluation of joint damage in patients with early
      rheumatoid arthritis (RA). METHODS: Radiographs of hands and feet of 30
      prospectively observed patients with early RA were assessed by the Rau method,
      the Larsen method, and count of erosive joints. The standardized response mean
      (SRM) was used to estimate the sensitivity to change of each method of
      assessment. RESULTS: Although the Rau method evaluates only the amount of bony
      erosion, nearly equivalent radiographic progression was observed with the Rau and
      the Larsen methods. Radiographic changes in the first year were sensitively
      identified by all 3 methods (SRM for Rau method 0.83, Larsen method 0.88, and
      count of erosive joints 0.84). However, in the period from 2 to 6 years after
      entry into the study, sensitivity to change was maintained with use of the Rau
      (SRM 1.38) and Larsen (SRM 0.95) methods, but not by count of erosive joints (SRM
      0.49). While an apparent ceiling effect was observed after 2 years in count of
      erosive joints, no ceiling effects were noted for the Rau and Larsen methods.
      CONCLUSION: Our study showed that the usefulness of the Rau method is equivalent
      to the Larsen method in clinical assessment of radiographic progression in early
      RA.

PMID- 11950008
TI  - Incidence of severe outcome in rheumatoid arthritis during 20 years.
AB  - OBJECTIVE: Information from successive inception cohorts is needed to reveal
      changes in the endpoint severity of rheumatoid arthritis (RA). We assessed joint
      destruction and disability 8-20 years after the onset of RA to estimate the
      number of patients with severe disease at the endpoint. METHODS: Radiographs of
      the hands and feet were taken at onset and at 1, 3, 8, 15, and 20 years from
      entry among 103 patients with recent onset (< 6 mo) seropositive RA. The Larsen
      score of 0-100 of 20 joints of hands and feet, the Health Assessment
      Questionnaire (HAQ) index, and the number of large joint arthroplasties were used
      to assess severity. The cumulative number of patients with amyloidosis was
      recorded. RESULTS: The median progression of small joint destruction was 2-3%
      yearly. At the endpoint 36% of the patients had Larsen score 50-100 and 23%
      scored 67-100. The endpoint HAQ index was 2-3 in 16% of the 81 patients
      investigated. The number of large joint arthroplasties was 29 in 16 patients. A
      high Larsen score or HAQ was registered in 30 (29%) patients. The incidence of
      amyloidosis was 13.6%; at the end of the 20 year followup 9 of the 14 patients
      with amyloidosis had died. CONCLUSION: Our prospective 20 year RA study is the
      first epidemiological survey in which 20 year severity in RA has been determined
      by 4 clinical measures; these data will serve as a basis for discussion of
      methods and comparison with other cohorts in the future.

PMID- 11950009
TI  - Repeated renal biopsy in proliferative lupus nephritis--predictive role of serum
      C1q and albuminuria.
AB  - OBJECTIVE: Proliferative (WHO III/IV) nephritis in systemic lupus erythematosus
      (SLE) is a severe disease manifestation for which treatment with cyclophosphamide
      and high dose corticosteroids is generally recommended. We investigated the
      effect of this standard treatment on renal histopathology and clinical and
      serological findings to determine if the therapeutic response could be predicted
      by these variables. METHODS: We studied 18 patients with SLE and proliferative
      nephritis in whom repeated renal biopsy was performed after termination of
      induction therapy with cyclophosphamide and corticosteroids. At the time of renal
      biopsy, renal function and albuminuria were determined and analyses of anti
      dsDNA, anti-C1q, and the complement factors C1q, C3 and C4 were performed.
      RESULTS: At repeated biopsy, 6/18 patients still had renal biopsy findings of WHO
      III/IV, 3 had transformed to WHO V, while 9 exhibited histopathological remission
      (WHO I/II). In the 9 patients with WHO III-V at the repeat biopsy, all but one
      patient had low C1q levels at the time of first biopsy and 5/9 at the repeat
      biopsy. In the 9 patients with WHO I/II at repeated biopsy, 4/9 had low C1q at
      first biopsy and none at the repeated biopsy (p = 0.0054 and p = 0.017 vs WHO III
      V at repeat and first biopsy, respectively). Albuminuria > or = 0.5 g/day
      combined with low C1q levels at repeat biopsy predicted persistent
      histopathological activity (WHO III-V). CONCLUSION: Despite aggressive
      immunosuppressive therapy, 9/18 patients still had active proliferative or
      membranous nephritis at a second renal biopsy. Serum C1q levels at both first and
      repeated renal biopsies were found to be a predictive marker of the
      histopathological outcome.

PMID- 11950010
TI  - Survey of antimalarial use in lupus pregnancy and lactation.
AB  - OBJECTIVE: To obtain the experience of selected experts in the use of
      antimalarial drugs (AM) in pregnancy and lactation in systemic lupus
      erythematosus. METHODS: Seventy-eight lupus experts identified from North America
      and UK were mailed a 19 question survey regarding their experience using AM in
      pregnancy and lactation. RESULTS: The 52 (67%) respondents with usable
      questionnaires treated a median of 75 lupus patients/year, including 4-5 lupus
      pregnancies/year. Thirty-five (69%) continued AM sometimes, often, or always
      during pregnancy. Continuing AM increased with the number of pregnant lupus
      patients seen (p < 0.01). None reported having seen any fetal toxicity with AM
      use, and pregnancy was never terminated because of AM, other than at patient
      insistence (n = 1). Postpartum, 29 (63%) continued AM and advised breast-feeding.
      Responses were consistent among North American and UK experts. CONCLUSION: The
      majority of lupus experts continue AM during pregnancy. This was particularly
      true for those who treated a larger number of pregnant lupus patients per year.
      The majority advise breast-feeding and continue AM postpartum. These practices
      are supported by the limited literature available.

PMID- 11950011
TI  - Effects of FTY720 in MRL-lpr/lpr mice: therapeutic potential in systemic lupus
      erythematosus.
AB  - OBJECTIVE To examine the effects of a novel immunosuppressant, FTY720, on
      hematolymphoid cells and the clinical course of MRL-lpr/lpr (MRL/lpr) mice
      genetically predisposed to systemic lupus erythematosus (SLE). METHODS: Apoptosis
      of hematolymphoid cells was determined in vitro by FACScan after staining with
      propidium iodide or merocyanine 540. From 4 months of age, 15 female MRL/lpr mice
      received oral administration of 2 mg/kg each of FTY720, methylprednisolone
      (mPSL), or vehicle, 3 times per week. Therapeutic efficacy was evaluated by
      levels of anti-dsDNA antibodies in serum and the survival rate. In parallel, T
      cell proliferation and secretion of interleukin 2 (IL-2) induced by anti-CD3,
      phenotypes of the spleen, lymph node and bone marrow cells, as well as
      immunohistochemistry of the kidney, were examined in vitro. RESULTS: FTY720 at 2
      microM induced apoptosis in more than 70% of double negative (CD4-/CD8-) T cells
      from the spleen of MRL/lpr mice in vitro. Oral FTY720 was tolerated well with no
      apparent side effects. FTY720 treated and control mice gained weight at an
      identical pace through to 9 months of age. FTY720 significantly suppressed the
      production of anti-dsDNA antibodies (FTY720 vs control: 1739 +/- 898 U/ml vs 410
      +/- 356 U/ml at 8 months of age; p < 0.05) and reduced the deposition of IgG in
      glomeruli compared to control animals. At 9 months of age, the survival rate in
      the FTY720 treated mice was 86.9% compared to 33.0% in controls (p < 0.01).
      FTY720 decreased the number of double negative T cells from the spleen and lymph
      nodes in vivo, and increased T cell proliferation and IL-2 secretion induced by
      anti-CD3 stimulation in vitro. CONCLUSION: FTY720 suppressed the development of
      autoimmunity and prolonged the lifespan of female MRL/lpr mice. Suppression of
      autoimmunity, at least in part, may have resulted from an apoptogenic potential
      of FTY720. Hence, it could be useful for primary or adjunctive therapy of human
      SLE.

PMID- 11950012
TI  - Subclinical myositis is common in primary Sjogren's syndrome and is not related
      to muscle pain.
AB  - OBJECTIVE: Although muscle pain is common in primary Sjogren's syndrome (SS), the
      underlying mechanisms are mainly unknown. We studied all patients with SS at our
      rheumatology unit with respect to muscle pain in general and to fibromyalgia
      (FM), and correlated clinical data to muscle biopsy findings. METHODS: We
      investigated 48 patients with SS according to the modified European diagnostic
      criteria. The ACR criteria for FM were used to subgroup the patients. Muscle
      biopsy was performed in 36 patients. Light microscope morphology and
      immunohistochemical expression of MHC class I, MHC class II, and membrane attack
      complex (MAC) were studied. RESULTS: We found 44% of patients complained of
      muscle pain; 27% fulfilled the ACR criteria for FM, whereas 17% had other forms
      of myalgia. Muscle pain could not be related to histopathological findings. Signs
      of inflammation were found in 26 of 36 biopsies (72%), and inflammation combined
      with degeneration/regeneration (i.e., histological signs of polymyositis) in 17
      biopsies (47%). However, only 5 patients (14%) had clinical as well as
      histological signs of polymyositis. Eight muscle biopsies (22%) showed
      histological features of inclusion body myositis (IBM). However, no patient had
      clinical symptoms suggestive of this disease. Abnormal expression of MHC class I,
      MHC class II, and MAC was found in 18 (50%), 16 (44%), and 27 (75%) patients,
      respectively. CONCLUSION: Muscle pain, especially FM, is common in SS.
      Histopathological signs of myositis are very common in SS. However, muscle
      symptoms are not related to histological signs of muscle inflammation. IBM-like
      findings may represent vacuolar myopathic degeneration due to previous
      subclinical muscle inflammation rather than a specific clinical entity.

PMID- 11950013
TI  - Raynaud's phenomenon in primary Sjogren's syndrome. Prevalence and clinical
      characteristics in a series of 320 patients.
AB  - OBJECTIVE: To determine the prevalence of Raynaud's phenomenon (RP) in a large
      series of patients with primary Sjogren's syndrome (SS) and to identify the
      clinical and immunological features related to its presence. METHODS: In a cross
      sectional study, we investigated 320 consecutive patients with primary SS (294
      women, 26 men; mean age at onset 60 yrs, range 16-87 yrs). All patients fulfilled
      4 or more of the diagnostic criteria for SS proposed by the European Community
      Study Group in 1993. Diagnosis of RP in patients with SS was defined as
      intermittent attacks of digital pallor and/or cyanosis in the absence of any
      other associated disease or anatomical abnormalities. RESULTS: RP was present in
      40 (13%) patients. All were women, with a mean age of 57 yrs (range 18-78). RP
      preceded onset of sicca symptomatology in 18 (45%) patients. The main triggering
      factor was exposure to cold, which induced RP in all patients, while emotional
      stress was a factor in 12 patients, as was job related predisposition in 2.
      Fifteen (38%) patients required pharmacological treatment with calcium channel
      blockers (12 patients) or angiotensin converting enzyme inhibitors (2 patients)
      during colder months, and one patient required treatment with intravenous
      prostacyclin for ischemic complications. Compared with SS patients without RP,
      those with RP showed a higher prevalence of articular involvement (50 vs 31%; p =
      0.031), cutaneous vasculitis (30 vs 11%; p = 0.003), antinuclear antibodies (95
      vs 65%; p < 0.001), anti-Ro/SSA (59 vs 31%; p < 0.001) and anti-La/SSB antibodies
      (44 vs 20%, p = 0.003). CONCLUSION: We found RP in 13% of patients with primary
      SS, in almost half of whom RP was the first autoimmune symptomatology. These
      patients constituted a subset of SS with a higher frequency of some
      extraglandular features and positive immunological markers. The clinical course
      of RP seems to be milder in patients with primary SS than in those with other
      systemic autoimmune diseases such as systemic sclerosis, with no vascular
      complications and pharmacological treatment needed in only 40% of patients.

PMID- 11950014
TI  - Cyclophosphamide pulse regimen in the treatment of alveolitis in systemic
      sclerosis.
AB  - OBJECTIVE: To evaluate, in a pilot study, the efficacy of a short term
      cyclophosphamide (CYC) pulse regimen on alveolitis in a cohort of patients with
      systemic sclerosis (SSc). METHODS: Twenty-three patients with SSc (17 diffuse SSc
      and 6 limited SSc) were selected in 5 centers in Italy, based on the findings of
      an abnormal bronchoalveolar lavage (BAL) cell analysis in association with
      altered pulmonary function tests (PFT) or recent deterioration in flow volume
      curve (FVC). Patients were also evaluated by skin score (Rodnan), esophageal
      manometry and barium swallow radiography, and electrocardiography and 2-mode
      echocardiography. The pre-enrolment pulmonary evaluation and after 6 months of
      therapy included evaluation of the clinical status, PFT (FVC, FEV1, DLCO), BAL.
      standard chest radiograph, and chest high resolution computed tomography. All
      patients received i.v. CYC (1000 mg/m2 of body surface monthly for 6 mo) and oral
      prednisone (25 mg daily for the first month and subsequently 5 mg daily of
      maintenance dosage for the remaining 5 mo). A complete blood count and urinalysis
      were obtained at monthly intervals. RESULTS: After 6 months of therapy the values
      for FVC did not change significantly. Individually, 8 of 23 patients showed an
      improvement (> 15% increase) in FVC after 6 months, while FVC in 13 cases
      remained stable. Only 2 patients had an important decline in FVC after 6 months
      of therapy (17 and 24% decrease). Improvement in DLCO was noted in 15 of 23
      patients after 6 months of therapy. Four patients were stable and 4 patients had
      a worsened DLCO at the end of the study. After therapy the mean value of BAL
      fluid recovery did not change. There was a reduction in total cell number
      although this value did not reach statistical significance. The levels of
      neutrophils, eosinophils, lymphocytes, and macrophages did not change
      significantly. Scans for patients with grades 1, 2, and 3 did not differ
      significantly after 6 months of therapy, and 14 patients were stable. Changes in
      appearance, in relation to changes in extent of disease, were seen in 8 patients
      and consisted of an extension of reticular pattern and transformation from grade
      1 to 2 (6/8 patients). All patients showed a ground-glass appearance indicating
      an acute alveolitis. Improvement in ground-glass was noted in 10 of 23 patients
      after 6 mo therapy. At the end of the study, 8 patients were stable and 5
      patients had a diffusion of the ground-glass to other segments. No side effects
      were experienced during the treatment except for mild nausea in 4 patients; no
      patients discontinued therapy during the study. CONCLUSION: CYC pulse regimen
      seems to stabilize alveolitis in the majority of cases. The association of CYC
      pulsed modality with prednisone may be useful in SSc patients to control disease
      evolution in the lung.

PMID- 11950015
TI  - Increased mortality due to cardiovascular disease in patients with giant cell
      arteritis in northern Sweden.
AB  - OBJECTIVE: To study the cause of death pattern in patients with giant cell
      arteritis (GCA) or polymyalgia rheumatica (PMR), and to analyze the effect of the
      disease, or its therapy, on the risk of a cardiovascular event (CVE). METHODS:
      Patients with biopsy proven GCA or with PMR, whose condition was diagnosed
      between 1973 and 1979, were followed until December 31, 1995. The standardized
      mortality ratio (SMR) was estimated using data for the population of
      Vasterbotten, Northern Sweden, as reference value. Information for sex, age at
      diagnosis, erythrocyte sedimentation rate (ESR) at diagnosis, corticosteroid
      therapy, comorbidity from diagnosis, and date and cause of death was collected.
      RESULTS: A total of 136 patients with GCA and 35 with PMR were identified. At the
      time of followup 114 patients with GCA and 25 with PMR were deceased. The overall
      mortality was significantly increased in the female patients, SMR = 133 (95% CI
      110-162). Death due to cardiovascular disease (CVD) was significantly increased
      in both women and men, SMR = 149 (95% CI 118-189) and 158 (95% CI 112-224),
      respectively, and mainly due to ischemic heart disease. An excess mortality was
      found in women with the highest ESR, the highest prescribed dose of prednisolone
      at diagnosis, or a daily prednisolone dose of 10 mg or more one year after
      diagnosis. In multiple Cox regression analysis, male sex and hypertension
      significantly increased the risk of a CVE. CONCLUSION: Death due to CVD was
      increased in patients with GCA. Increased mortality was related to either the
      corticosteroid therapy itself or insufficient control of inflammation.

PMID- 11950016
TI  - A study among related pairs of Japanese patients with familial Behcet's disease:
      group comparisons by interval of disease onsets.
AB  - OBJECTIVE: To investigate the relationship between clinical features and the
      interval between onset of disease in pairs of related Japanese patients with
      Behcet's disease (BD). METHODS: Questionnaires were sent to hospitals in which
      patients with familial occurrence of BD had been treated according to previous
      nationwide hospital surveys, and to an additional 341 hospitals selected at
      random. RESULTS: A total of 35 patients (19 male, 16 female) in 17 families (19
      related pairs) were reported. The positive rate of HLA-B51 was 60.9% (14/23). The
      familial pairs were divided into 2 groups, with the mean interval between disease
      onset between each pair being either < or = 9 years or > or = 10 years. Among the
      short interval group, the total number of clinical findings and difference in age
      of onset was significantly larger than the long interval group. The interval
      between onsets had a high positive correlation with concordance of clinical
      findings and a high negative correlation with the difference in onset age.
      Difference in onset age had a higher negative correlation with same sex.
      Moreover, age difference had a high negative correlation with HLA-B5 (B51).
      Analysis of data showed that the related pairs with the short interval between
      onsets had larger difference in onset age and greater concordance of symptoms
      than the long interval patients. CONCLUSION: Although our findings did not show
      any direct evidence of an environmental cause in the etiology of BD, we speculate
      that there may be a multifactorial etiology including genetic factors such as HLA
      B51 positivity.

PMID- 11950017
TI  - Adrenal gland hypofunction in active polymyalgia rheumatica. effect of
      glucocorticoid treatment on adrenal hormones and interleukin 6.
AB  - OBJECTIVE: To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in
      patients with recent onset polymyalgia rheumatica (PMR) not previously treated
      with glucocorticoids; and to detect possible correlations between adrenal hormone
      levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and
      during 12 months of glucocorticoid treatment. METHODS: Forty-one PMR patients of
      both sexes with recent onset disease and healthy sex and age matched controls
      were enrolled into a longitudinal study. Patients were monitored for serum
      cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and
      clinical and laboratory measures of disease activity such as C-reactive protein
      and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of
      glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and
      plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8
      patients with recent onset PMR not treated with glucocorticoid in comparison to
      controls after challenge with ovine corticotropin releasing hormone (oCRH) test.
      In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were
      evaluated after stimulation with low dose (1 microg) intravenous ACTH. RESULTS:
      Serum cortisol and ASD levels of all PMR patients at baseline did not differ from
      controls. During followup, cortisol levels dipped at one and 3 months. Serum
      DHEAS levels in all patients were significantly lower than in controls at
      baseline. In female PMR patients a significant correlation was found at baseline
      between cortisol levels and duration of disease. Serum concentrations of IL-6 at
      baseline were significantly higher in PMR patients than in controls. During 12
      months of glucocorticoid treatment IL-6 levels dropped significantly at one
      month; thereafter they remained stable and did not increase again despite
      tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol
      response was found in patients and controls. After ACTH administration, a
      significant cortisol peak was detected in patients and controls, whereas no
      significant difference in cortisol area-under-the-curve (AUC) was found between
      the groups. In contrast, ACTH induced a significantly higher (p < 0.05) peak of
      17-OHP and AUC in PMR patients than in controls. CONCLUSION: This study found
      reduced production of adrenal hormones (cortisol, DHEAS) at baseline in patients
      with active and untreated PMR. The defect seems mainly related to altered adrenal
      responsiveness to the ACTH stimulation (i.e., increased 17-OHP), at least in
      untreated patients. The 12 month glucocorticoid treatment of patients reduced the
      production of inflammatory mediators (i.e., IL-6) in a stable manner that
      persisted after glucocorticoids were tapered.

PMID- 11950018
TI  - Risk factors for the development of psoriatic arthritis: a population based
      nested case control study.
AB  - OBJECTIVE: To identify factors influencing the development of psoriatic arthritis
      (PsA) in a population-based, inception cohort of psoriasis (PS) patients.
      METHODS: Using the population-based data resources of the Rochester Epidemiology
      Project. which ensures virtually complete ascertainment of all clinically defined
      conditions, we previously identified all incident cases of PsA and prevalent
      cases with PS from 1/1/1982 to 12/21/1991. In this nested case-control study, we
      assessed potential factors influencing the development of PsA in this cohort
      using medical record and patient survey information. Each case of PsA was matched
      with 2 PS controls on age, gender and PS duration/date of onset. Factors
      influencing the development of PsA were identified, adjusting for the influence
      of other variables using conditional logistic regression for medical record data
      and logistic regression for survey data. RESULTS: Sixty incident PsA cases were
      matched with 120 controls with PS. The median age at onset of PS was 31.7 (3.0
      78.3) years, and 49% of subjects were male. There were 67% (n = 40) survey
      responders among cases and 48% (n = 58) among controls. Corticosteroids were used
      by 10 cases and 6 controls in the 2 years prior to onset of PS through to the
      development of PsA, and increased the risk of developing PsA (odds ratio 4.33,
      95% CI = 1.34-14.02). Pregnancy occurred in 2 cases and 12 controls in the same
      period, and decreased the risk of developing PsA (odds ratio 0.19, 95% CI = 0.04
      0.95). These associations remained significant after adjusting for the influence
      of gender, age, and duration of psoriasis. CONCLUSION: Corticosteroid use and
      pregnancy, both of which modulate the immune response, may influence the
      development of PsA in patients with PS.

PMID- 11950019
TI  - The effect of a home based exercise intervention package on outcome in ankylosing
      spondylitis: a randomized controlled trial.
AB  - OBJECTIVE: Home based self-care is essential for successful management of
      ankylosing spondylitis (AS). We designed an intervention package aimed at
      promoting self-care and regular longterm exercise and evaluated its effect on
      outcome. METHOD: Members of our database (n = 4569) were randomly selected and
      randomized to an intervention group (IG) or a followup control group (CG). The
      intervention consisted of an exercise/information video, exercise progress chart,
      patient education booklet, and AS exercise reminder stickers. The outcome
      measures were function (BASFI), disease activity (BASDAI), global well being (BAS
      G), exercise self-efficacy (ESE), arthritis self-efficacy (SES), and quantity of
      AS mobility/aerobic exercise assessed at baseline and 6 months. RESULTS: Of the
      200 subjects, 155 completed the study (75 IG and 80 CG). Baseline analysis showed
      no differences between the CG and the IG. At 6 months, analysis revealed no
      statistically significant between-group differences for the BASFI, BASDAI, and
      BAS-G. although the p value of 0.08 for function approached significance. Self
      efficacy for exercise showed a significant improvement in the IG (p = 0.045).
      There were no between-group differences for the SES pain and other symptoms
      subscales. Finally, there was a significant increase in self-reported AS mobility
      (p < 0.001) and aerobic exercise (p < 0.05) in the IG. CONCLUSION: An exercise
      intervention package designed to promote self-management in AS (1) significantly
      improves self-efficacy for exercise; (2) significantly improves self-reported
      levels of exercise; (3) reveals a trend for improvement in function (BASFI).

PMID- 11950020
TI  - High frequency of reactive joint symptoms after an outbreak of Salmonella
      enteritidis.
AB  - OBJECTIVE: To study reactive symptoms following an outbreak of Salmonella
      enteritidis that occurred after a dinner party held January 15, 1999, in
      Copenhagen, Denmark. An epidemiological study pointed toward a dish of minced raw
      salmon, in which one of the constituents was unboiled eggs as the likely cause of
      the outbreak. Remnants of this dish were not available for bacteriological exam.
      METHOD: All 94 guests and kitchen staff members were mailed a questionnaire about
      gastrointestinal, joint, and eye symptoms. Nonrespondents were contacted by
      telephone. Thirty-five individuals delivered blood samples for serological
      analysis mean 90 days (range 60-186) after the exposure. RESULTS: Answers were
      obtained from all participants and 91 were regarded as Salmonella exposed.
      Male/female ratio was 40/51, mean age 49 years. Fifty-two reported diarrhea
      (57%), 49 abdominal pain (54%), 33 fever (36%), and 12 vomiting (13%). Eight (9%)
      delivered stool samples, and all were positive for S. enteritidis. Seventeen
      fulfilled predefined criteria of reactive arthritis/arthralgia (ReA), and of
      these 13 had had enterocolitis. Joint pain from knees and ankles was most
      frequently reported. The mean duration of diarrhea among the patients reporting
      joint symptoms was 7.5 days, while in the group of patients with enterocolitis
      without joint symptoms it was 4.1 days (p = 0.00047). Three participants, all
      from the ReA group, reported ocular redness and irritation compatible with
      conjunctivitis. Although there was a trend to higher IgG anti-Salmonella antibody
      levels among the patients with ReA the difference was not significant.
      CONCLUSION: Reactive joint symptoms after food-borne Salmonella infection may be
      more frequent than previously thought. The duration of diarrhea is strongly
      correlated with the occurrence of joint symptoms.

PMID- 11950021
TI  - Metabolism of human articular chondrocytes cultured in alginate beads. Longterm
      effects of interleukin 1beta and nonsteroidal antiinflammatory drugs.
AB  - OBJECTIVES: To investigate the longterm effects (12 days) of nonsteroidal
      antiinflammatory drugs [NSAID: aceclofenac (ACECLO), sodium diclofenac (DICLO),
      indomethacin (INDO), nimesulide (NIM), rofecoxib (ROFE), celecoxib (CELE),
      piroxicam (PIROX), and ibuprofen (IBUP)] on the metabolism of human chondrocytes
      cultured in alginate beads. METHODS: Enzymatically isolated osteoarthritic (OA)
      chondrocytes were cultured in alginate beads in a well defined culture medium for
      12 days. The DNA content was measured according to a fluorimetric method and cell
      proliferation was determined by the incorporation of 3H-thymidine in the newly
      synthesized DNA. Interleukin 6 (IL-6) and IL-8, stromelysin [matrix
      metalloproteinase-3 (MMP-3)], and aggrecan (AGG) production were assayed by
      specific enzyme amplified sensitivity immunoassays, and prostaglandin E2 (PGE2)
      production by specific radioimmunoassay. All NSAID were tested at the mean peak
      plasma concentration (Cmax) obtained after oral administration of a therapeutic
      dose. RESULTS: In alginate beads, chondrocytes synthesized high amounts of AGG,
      which were largely (98%) immobilized in the alginate matrix. A large amount (43%)
      of the IL-8 produced was stored in the alginate beads, whereas almost all IL-6
      production (94%) was released in the culture supernatant. At the therapeutic
      concentration, all NSAID tested fully blocked PGE2 production. ACECLO, DICLO,
      INDO, NIM significantly inhibited basal and IL-1beta stimulated IL-6 production;
      CELE and IBUP only inhibited IL-1beta stimulated IL-6 production; and ROFE and
      PIROX had no significant effects. No NSAID showed significant effects on basal
      and IL-1beta stimulated IL-8 production, except CELE and IBUP, which slightly
      increased basal IL-8 production. ACECLO and INDO increased AGG content by 25% in
      the alginate beads, while the other NSAID were without significant effect. No
      NSAID were able to modify the inhibitory effect of IL-1beta on AGG production.
      NSAID did not modify MMP-3 production. CONCLUSION: The mechanism of action of
      NSAID seems to be multifactorial and not limited to the inhibition of
      cyclooxygenases. Further, in our culture conditions, at the Cmax and by
      comparison with other NSAID, ACECLO and INDO show an advantageous activity
      profile. They fully blocked PGE2 production, inhibited IL-6 synthesis, and
      increased aggrecan synthesis. These effects appear advantageous for the longterm
      treatment of chronic joint diseases such as osteoarthritis.

PMID- 11950022
TI  - A comparative study of telephone versus onsite completion of the WOMAC 3.0
      osteoarthritis index.
AB  - OBJECTIVE: Outcome assessment in clinical trials using the Western Ontario and
      McMaster University (WOMAC 3.0) Osteoarthritis Index is traditionally achieved
      through self-administration of the Index. However, in other areas of clinical
      measurement, telephone administration has been shown to be a reliable method of
      acquiring data that are both accurate and complete. To address this issue in knee
      osteoarthritis (OA), we conducted a comparative study of telephone administration
      by interviewer of WOMAC LK3.0 versus onsite self-completion at the hospital.
      METHODS: Fifty consenting patients with knee OA were randomized to complete the
      WOMAC LK3.0 Index by telephone interview one day, followed by onsite completion
      the following day, or vice versa. Neither patients nor interviewers had access to
      any prior scores. RESULTS: The mean age of the 50 patients was 66.3 years (range
      44-82); 34 (68%) were female and 16 (32%) male. There was excellent agreement
      between the mean office and telephone scores, with mean differences for the WOMAC
      LK3.0 pain, stiffness, and function subscale scores and total score of 0.09,
      0.12, 0.78, and 0.98, respectively. These differences were well within the
      respective protocol defined equivalence criteria of +/- 1.7, +/- 0.9, +/- 6.4,
      and +/- 9.1, and represented differences from office scores of 0.9, 2.6, 2.4, and
      2.2%, respectively. CONCLUSION: The use of telephone interviews for the WOMAC
      LK3.0 Index is a valid method of obtaining OA outcome measurements. These
      observations have important implications for designing data acquisition
      strategies for future OA clinical trials and for longterm observational studies.

PMID- 11950023
TI  - Reduction of tumor necrosis factor induced nuclear factor-kappaB nuclear
      translocation and DNA binding by dexamethasone in human osteoarthritic synovial
      tissue explants.
AB  - OBJECTIVE: The antiinflammatory effects of glucocorticoids are mediated by
      several mechanisms, including inhibition of nuclear factor-kappaB (NF-kappaB)
      nuclear translocation and DNA binding. This mechanism is not evident in some cell
      types, including endothelial cells and rheumatoid arthritis (RA) fibroblast-like
      synoviocytes (FLS). We determined the effect of glucocorticoids and tumor
      necrosis factor (TNF) on nuclear localization and DNA binding of the
      transcription factor NF-kappaB in osteoarthritic (OA) synovial tissue. METHODS:
      Explants of synovial tissue from patients undergoing joint replacement surgery
      for arthritis were placed in culture and treated with dexamethasone 10(-6) M for
      18 h and again at 30 min prior to stimulation with TNF for a further 30 min. NF
      kappaB and AP-1 DNA binding activities were determined by electrophoretic
      mobility shift analysis of nuclear extracts prepared from 6 whole tissue
      explants. Nuclear localization of NF-kappaB was determined by quantitative
      immunohistochemistry for Rel-A(p65) in thin sections of 5 synovial tissue
      explants. RESULTS: TNF induced NF-kappaB nuclear translocation and DNA binding in
      all OA synovial tissue explants, although there were no consistent effects on AP
      1 DNA binding. Dexamethasone reduced TNF stimulated nuclear translocation of
      RelA(p65) in all 5 OA synovial explants analyzed by immunohistochemistry.
      Dexamethasone partially decreased NF-kappaB DNA binding in 5 of 6 TNF stimulated
      explants and 4 of 6 unstimulated explants. In cultured rheumatoid arthritis and
      OA fibroblast-like synoviocytes and Mono Mac 6 cells the effects of dexamethasone
      on NF-kappaB DNA binding were not evident. CONCLUSION: Dexamethasone partially
      inhibits TNF induced NF-kappaB DNA binding in human synovial tissue. It is
      feasible to use explants of intact fresh human synovium as a substrate for the
      action of antirheumatic drugs targeting a transcription factor.

PMID- 11950024
TI  - Dense innervation in pseudocapsular tissue compared to aneural interface tissue
      in loose totally replaced hips.
AB  - BACKGROUND: The function of many inflammatory cells is in part regulated by
      neuronal cells, which may lead to so-called neurogenic inflammation. Sensory
      nerves also mediate the pain sensation. METHODS: This immunohistochemical study
      focused on visualization of C-sensory and sympathetic innervation in the synovial
      membrane-like interface and pseudocapsular tissue around loosened total hip
      replacement. RESULTS: The synovial membrane-like interface did not contain C
      sensory peptidergic or sympathetic neural structures. Only limited attempts to
      neural regeneration were detected. In contrast, pseudocapsule expressed dense
      innervation with strong CPON-ir sympathetic innervation and osteoarthritis also
      had C-sensory fibers. Intense neural regeneration was seen in these synovial
      membranes. Surprisingly, stellate and/or highly dendritic fibroblast-like cells
      in the fibrotic areas in the interface tissue expressed strong immunoreactivity
      to the neural marker PGP 9.5, ubiquitin carboxyterminal hydrolase. CONCLUSION:
      Pain related to aseptic loosening cannot arise in the aneural interface membrane.
      Inflammation in interface/aseptic loosening seems to be driven by non-neurogenic
      factors, such as foreign bodies and micromovement. Insufficient lysosomal
      degradation of denatured proteins causes accumulation of ubiquitinated conjugates
      and enzymes involved in the process. This leads to insufficient degradation of
      platelet derived growth factor (PDGF)-receptor complex and can contribute to the
      accumulation of connective tissue in the interface. Failure in ubiquitin mediated
      proteolysis might support overgrowth of interface tissue and aseptic loosening.

PMID- 11950025
TI  - A metaanalysis of severe upper gastrointestinal complications of nonsteroidal
      antiinflammatory drugs.
AB  - OBJECTIVE: Prior metaanalyses of the risk of upper gastrointestinal (GI)
      complications associated with nonsteroidal antiinflammatory drugs (NSAID) have
      focused on the published English language epidemiologic literature and/or only a
      portion of the relevant evidence, restrictions that are now known to be
      associated with bias in metaanalysis. We synthesized the published and
      unpublished evidence to determine the least biased estimates of the risks of
      perforations, ulcers, and bleeds (PUB) associated with NSAID use from all study
      designs and all languages. METHODS:  DATA SOURCES: Using MEDLINE, EMBASE,
      HEALTHSTAR, and BIOSIS, we searched for English and non-English language studies
      of NSAID from 1966-1998 reporting primary data on GI complications. We obtained
      unpublished data from the US Food and Drug Administration (FDA) new drug
      application (NDA) reviews. NDA were hand searched to identify unpublished studies
      with inclusion criteria identical to those used for published reports. STUDY
      SELECTION: Studies had to assess the use of oral NSAID for more than 4 days
      duration in subjects > 18 years of age and report on the clinically relevant
      upper GI outcomes of PUB. RESULTS: Two reviewers evaluated 4881 published titles
      and identified 13 NSAID versus placebo randomized clinical trials and 3
      previously unpublished FDA placebo controlled randomized controlled trials, 9
      cohort studies, and 23 case control studies sufficiently clinically homogeneous
      to pool. Two reviewers extracted data about study characteristics and study
      quality. DATA SYNTHESIS: The majority of clinical trials were of good quality,
      but observational studies had methodologic limitations. The pooled odds ratio
      (OR) from 16 NSAID versus placebo clinical trials, comprising 4431 patients, was
      5.36 (95% CI: 1.79, 16.1). The pooled relative risk of PUB from 9 cohort studies
      comprising over 750,000 person-years of exposure was 2.7 (95% CI: 2.1, 3.5). The
      pooled OR of PUB from 23 case control studies using age and sex matching,
      representing 25,732 patients, was 3.0 (95% CI: 2.5, 3.7). Data were insufficient
      to justify subgroup analyses stratified by age, comorbid conditions, drug, or
      dose. CONCLUSION: These data support an association between the use of NSAID and
      serious upper GI complications, including estimates from different study designs.
      Prior pooled estimates about the effect of patient and drug variables on
      increased risk must be viewed with caution.

PMID- 11950026
TI  - Teaching clinical skills in musculoskeletal medicine: the use of structured
      clinical instruction modules.
AB  - OBJECTIVE: To assess student evaluation, satisfaction, and examination outcomes
      for a new method of teaching musculoskeletal (MSK) medicine clinical skills,
      structured clinical instruction modules (SCIM), and to compare with the outcomes
      of a traditional method of teaching clinical skills (small group bedside
      tutorials). METHODS: Year 2 students in a 4 year graduate medical school were
      taught using the method of bedside senior registrar teaching, supplemented by
      outpatient attendances in 1997 and by SCIM in 2000. All students in 1997 and 2000
      were debriefed at the end of each unit of clinical skills teaching for student
      feedback on their teaching experience using a standardized questionnaire. At the
      end of the academic year, all students underwent an objective structured clinical
      examination (OSCE) in clinical skills that included rheumatology (hand
      examination) and orthopedic surgery (knee examination) stations. The effect of
      the method of teaching on the students' performance in the rheumatology (hand)
      and orthopedic surgery (knee) stations was analyzed. RESULTS: Sixty-seven
      students were taught clinical skills and completed the OSCE in 1997 and 78
      students were taught clinical skills by SCIM and completed the OSCE in 2000. The
      teaching of orthopedics using traditional methods was poor, but there was no
      difference in satisfaction between traditional methods of teaching and SCIM for
      orthopedic surgery and rheumatology. There was no statistically significant
      difference in the performance of students in the hand OSCE stations in 2000
      compared to the same station in 1997. There was a small but statistically
      significant difference in the performance of students in 1997 and 2000 in the
      knee station, the 1997 students performing better in this station. CONCLUSION:
      The SCIM is an effective method of teaching clinical skills in MSK medicine,
      comparable with patient partners and traditional registrar based bedside teaching
      methods, but it is less resource intensive.

PMID- 11950027
TI  - Chronic widespread pain: a three year followup of pain distribution and risk
      factors.
AB  - OBJECTIVE: To describe the change of pain reports over time in 3 cohorts derived
      from the general population: (1) no chronic pain (NCP; n = 1156); (2) chronic
      regional pain (CRP; n = 502); and (3) chronic widespread pain (CWP; n = 242). To
      identify risk factors that predict the development or persistence of chronic
      widespread pain. METHODS: A 3-year followup from 1995 to 1998 with postal
      questionnaire to 2425 subjects of both sexes aged 20-74 years on the west coast
      of Sweden. RESULTS: At followup, a larger proportion of subjects with initial CRP
      compared to initial NCP reported CWP (16.4 and 2.2%, respectively; p < 0.001).
      The majority of subjects (56.9%) who primarily reported CWP remained in that
      group at followup, but 26.8% had changed status to CRP and 16.3% to NCP. The
      number of painful regions (7-12 vs 0 regions) reported at baseline was the
      strongest predictor for the development of CWP with an odds ratio (OR) of 12.13
      (95% CI 4.47-32.88). The development of CWP was also predicted by higher age (OR
      = 3.13, 95% CI 1.47-6.69, age-group 59-74 years vs age-group 20-34 years), and a
      family history of chronic pain (OR = 1.87, 95% CI 1.14-3.07). A habit of drinking
      alcohol weekly (OR = 0.42, 95% CI 0.21-0.85) compared to the habit of never or
      seldom drinking alcohol was protective, as well as having personal social support
      (OR = 0.49, 95% CI 0.28-0.85). The persistence of CWP was predicted by the number
      of painful regions (13-18 vs 1-6 regions) at baseline (OR = 7.56, 95% CI 2.17
      26.30), and being an immigrant (OR = 3.22, 95% CI 1.33-7.77). CONCLUSION:
      Although the overall prevalence of CWP was stable over a 3-year period there was
      a considerable variation on an individual basis. This variability in expressing
      CWP was moderately predicted by a combination of risk factors, the most important
      being the number of painful regions at baseline. Future research will need to
      show how useful the identified factors are in clinical practice and whether
      intervention aimed at changing these factors will improve pain outcome.

PMID- 11950028
TI  - Serum and synovial fluid concentrations of matrix metalloproteinases 3 and its
      tissue inhibitor 1 in juvenile idiopathic arthritides.
AB  - OBJECTIVE: Matrix metalloproteinases (MMP) are a large family of proteolytic
      enzymes involved in the remodeling of extracellular matrix during tissue
      resorption in idiopathic arthritides. We investigated serum and synovial fluid
      (SF) concentrations of MMP-3 and its tissue inhibitor (TIMP-1) in juvenile
      idiopathic arthritides (JIA). METHODS: Sera from 45 patients with active, 15
      patients with inactive JIA, and 15 healthy controls were evaluated by ELISA for
      MMP-3 (stromelysin-1), TIMP-1, and soluble p75 tumor necrosis factor receptor
      (sTNFR). Paired SF concentrations were evaluated in 19 patients with JIA.
      RESULTS: MMP-3 serum concentrations were significantly higher in patients with
      active poly- and oligoarticular JIA versus inactive patients (p = 0.04 and p =
      0.02, respectively) and healthy controls (p < 0.001 for both). Serum MMP-3, but
      not TIMP-1, concentration displayed a variable degree of correlation with
      clinical and laboratory variables of disease activity and with p75 sTNFR
      concentrations (r = 0.37, p = 0.005). SF MMP-3 concentrations were 30-300 times
      higher than those found in paired sera (p < 0.001, Wilcoxon rank test). A clear
      inversion of MMP-3/TIMP-1 ratio was observed when sera (median 0.31. range 0.02
      1.5) were compared with the corresponding SF samples (5.3, range 4.9-5.5; p <
      0.001). CONCLUSION: MMP-3 (stromelysin-1) is clearly overexpressed in SF of
      patients with JIA. An inadequate counter-expression of TIMP-1 may represent a
      crucial event for the development and perpetuation of tissue damage.

PMID- 11950029
TI  - Soluble adhesion molecules in pediatric rheumatic diseases.
AB  - OBJECTIVE: To determine serum levels of adhesion molecules ICAM-1, ICAM-3, VCAM
      1, L-selectin, and E-selectin in children with a variety of pediatric rheumatic
      diseases and investigate their relationship to clinical disease activity.
      METHODS: Retrospective review of records of 18 children with rheumatic diseases
      who had banked sera available for study. Eight children had systemic lupus
      erythematosus (SLE), 2 mixed connective tissue disease, 4 dermatomyositis (DM),
      and 4 various forms of vasculitis. Levels of the soluble adhesion molecules were
      determined by sandwich ELISA. Levels were compared among patients with the
      various diagnoses and between patients with active vs inactive disease. Levels
      were also correlated with erythrocyte sedimentation rate in all patients; C3, C4,
      and total hemolytic complements and anti-dsDNA antibodies in SLE; and creatine
      phosphokinase, aldolase, and von Willebrand factor (vWF) antigen levels in DM.
      Levels also correlated with disease activity scores, which varied by diagnosis.
      RESULTS: A trend toward higher levels of sE-selectin was found in vasculitis vs
      other diagnoses (p = 0.08). sICAM-1 was higher in patients with active vs
      inactive disease (p = 0.05) across all diagnoses. L-selectin levels correlated
      with C4 complement levels in SLE patients (r = 0.76, p = 0.03), and there was a
      trend toward an inverse correlation between levels of sE-selectin and vWF (r = 
      0.93, p = 0.08). There was no direct correlation of the adhesion molecule levels
      with any of the disease activity scores. CONCLUSION: The small number of patients
      and retrospective design of this study mean that any results must be interpreted
      with caution. We conclude: (1) Elevated E-selectin levels in vasculitis likely
      reflect the high degree of endothelial activation and possibly overt vascular
      damage in those conditions. (2) The correlation of sL-selectin with C4 in SLE may
      indicate that downregulation of shedding of cell surface L-selectin is involved
      in continued adherence of leukocytes to endothelium, possibly causing further
      damage and immune complex deposition in this condition. (3) The trend toward
      inverse correlation between sE-selectin and vWF:Ag in DM is curious, but may show
      that the role of endothelium in the pathophysiology of this disease is different
      from those such as vasculitis. (4) Levels of sICAM- I may be a useful marker of
      active vs quiescent disease in general in the pediatric rheumatic diseases,
      although lack of correlation with disease activity indices may indicate that it
      is too insensitive to smaller differences in disease activity to be recommended
      for routine clinical use.

PMID- 11950031
TI  - Perioperative medical management of antiphospholipid syndrome: hospital for
      special surgery experience, review of literature, and recommendations.
AB  - Patients with antiphospholipid syndrome (APS), who are predisposed to vascular
      thrombotic events, are at additional risk for thrombosis when they undergo
      surgery. Serious perioperative complications (recurrent thrombosis, catastrophic
      exacerbation, or bleeding) occur despite prophylaxis. We describe our
      perioperative experience with APS patients who underwent a variety of surgeries,
      review the literature, and discuss strategies that may guide other physicians in
      their perioperative evaluation and management of patients with APS.
      RECOMMENDATIONS: perioperative strategies should be clearly identified before
      surgical procedure; pharmacological and physical antithrombosis interventions
      vigorously employed; periods without anticoagulation kept to a minimum; and any
      deviation from a normal course should be considered a potential disease related
      event.

PMID- 11950030
TI  - High prevalence of hyperuricemia in adolescent Taiwan aborigines.
AB  - OBJECTIVE: To explore the prevalence and related factors of hyperuricemia among
      adolescent Taiwan aborigines in tribes with a high prevalence of adult gout,
      compared with adolescents of low prevalence aboriginal and non-aboriginal tribes.
      METHODS: The participants were aborigines and non-aborigines in Taiwan, age 12 to
      15 years and free of gout. Each participant provided information on sex, age, and
      parents' tribal background as well as body weight and height. Serum samples were
      analyzed for biochemical markers. A logistic regression model was used to study
      factors related to hyperuricemia. RESULTS: In total 940 adolescents participated.
      The hyperuricemia rate in tribes with high gout prevalence (57.7%) was higher
      than in non-aborigines (48.2%) and in aboriginal tribes with low gout prevalence
      (34.0%). Factors statistically significantly related to hyperuricemia were tribe,
      sex, obesity, creatinine, and cholesterol levels in preliminary analysis. After
      adjustment by the logistic regression model, obese boys with higher creatinine
      were most likely to have hyperuricemia. Adolescents whose parents originated from
      tribes with high gout prevalence had a tendency to have hyperuricemia, and those
      aborigines from tribes with low gout prevalence had a low prevalence of
      hyperuricemia compared to non-aborigines. CONCLUSION: The prevalence of
      hyperuricemia in aboriginal adolescents mirrors the incidence of adult gout,
      implying a predisposition for adult gout in childhood, with genetic and/or
      environmental components presumably contributing to the differences between
      tribes; this may be of potential benefit to preventive efforts.

PMID- 11950032
TI  - Application of eye drops by patients with rheumatoid arthritis.

PMID- 11950033
TI  - Inconstant bursa between head of 5th metatarsal bone and tendon of abductor
      digiti minimi in psoriatic arthritis.

PMID- 11950034
TI  - Fifty years of cortisone.

PMID- 11950035
TI  - Visual hallucinations and the risk of visual loss in patients with giant cell
      (temporal) arteritis.

PMID- 11950036
TI  - Local injections in polymyalgia rheumatica.

PMID- 11950037
TI  - Isolated tuberculosis monoarthritis mimicking juvenile rheumatoid arthritis.

PMID- 11950038
TI  - Termination of disease modifying antirheumatic drugs in psoriatic arthritis.

PMID- 11950039
TI  - Myocarditis associated with polymyositis diagnosed by gadolinium-DTPA enhanced
      magnetic resonance imaging.

PMID- 11950040
TI  - Ultrasound imaging--a requirement for rheumatologists.

PMID- 11950041
TI  - Canadian Consensus Conference on hydroxychloroquine.

PMID- 11950042
TI  - Structure and properties of Ti-7.5Mo-xFe alloys.
AB  - The present work is a study of a series of Ti-7.5Mo-xFe alloys, with the focus on
      the effect of iron addition on the structure and mechanical properties of the
      alloys. Experimental results indicate that alpha" phase-dominated binary Ti-7.5Mo
      alloy exhibited a fine, acicular martensitic structure. When 1 wt% or more iron
      was added, the entire alloy became equi-axed beta phase structure with a grain
      size decreasing with increasing iron content. A thermal omega phase was formed in
      the alloys containing iron of roughly between 0.5 and 3 wt%. The largest quantity
      of omega phase and highest microhardness were found in Ti-7.5Mo-1Fe alloy. The
      binary Ti 7.5Mo alloy had a lower microhardness, bending strength and modulus
      than all iron-containing alloys. The largest bending strength was found in Ti
      7.5Mo-2Fe alloy. The present alloys with iron contents of about 2-5 wt% seem to
      have a great potential for use as an implant material.

PMID- 11950043
TI  - Tissue ingrowth and degradation of two biodegradable porous polymers with
      different porosities and pore sizes.
AB  - Commonly, spontaneous repair of lesions in the avascular zone of the knee
      meniscus does not occur. By implanting a porous polymer scaffold in a knee
      meniscus defect, the lesion is connected with the abundantly vascularized knee
      capsule and healing can be realized. Ingrowth of fibrovascular tissue and thus
      healing capacity depended on porosity, pore sizes and compression modulus of the
      implant. To study the lesion healing potential, two series of porous
      polyurethanes based on 50/50 epsilon-caprolactone/L-lactide with different
      porosities and pore sizes were implanted subcutaneously in rats. Also, in vitro
      degradation of the polymer was evaluated. The porous polymers with the higher
      porosity, more interconnected macropores, and interconnecting micropores of at
      least 30 microm showed complete ingrowth of tissue before degradation had
      started. In implants with the lower macro-porosity and micropores of 10-15 microm
      degradation of the polymer occurred before ingrowth was completed. Directly after
      implantation and later during degradation of the polymer, PMN cells infiltrated
      the implant. In between these phases the foreign body reaction remained
      restricted to macrophages and giant cells. We can conclude that both foams seemed
      not suited for implantation in meniscal reconstruction while either full ingrowth
      of tissue was not realized before polymer degradation started or the compression
      modulus was too low. Therefore, foams must be developed with a higher compression
      modulus and more connections with sufficient diameter between the macropores.

PMID- 11950044
TI  - Passivation of nitinol wire for vascular implants--a demonstration of the
      benefits.
AB  - This study investigated a passivation process for polished nitinol wires and
      vascular stent components, after being given a typical shape setting heat
      treatment. Heat treated samples were passivated in a nitric acid solution and a
      series of corrosion tests, surface analysis and chemical analysis was performed.
      Potentiodynamic polarization tests demonstrated a significant increase in
      breakdown potential for passivated samples, compared to heat treated surfaces.
      Surface analysis indicated that the passivation reduces Ni and NiO content in the
      oxide and increases TiO2 content. Chemical analysis of passivation solutions
      suggests that the improvement in corrosion resistance is proportional to the
      quantity of nickel removed. Long term immersion tests demonstrate that nickel
      release from the surface of the material decreases with time and the quantity of
      nickel released is lower for passivated samples. The improved corrosion
      resistance is maintained after extended periods of immersion in saline solution.

PMID- 11950045
TI  - Polyetheretherketone--cytotoxicity and mutagenicity in vitro.
AB  - The results of the incubation of polyetheretherketone (PEEK) fibre material with
      seven different genotype variants of salmonella bacterium showed with and without
      an external metabolic activation system (S9) with no mutagenic or cytotoxic
      activity of the test material. In the so-called "plate incorporation test" in
      which the PEEK raw material is finely cut and applied direct to the agar plate
      without the addition of solvent there was, as expected, no evidence of cytotoxic
      or mutagenic effects. In the HPRT test there was a significant increase in the
      number of mutants per dish, both after addition of N-acetylaminofluorene and N
      methyl-N'-nitro-N-nitrosoguanidine (with and without an external metabolic
      activation system = +S9), but not after treatment of the cells with PEEK-DMSO
      eluate. This means that the PEEK material under study did not release any
      substances that cause V79 cells to mutate. The investigation of the toxic
      reaction on the material under study revealed that the number of surviving
      colonies per 10(5) surviving cells lay within the range of or below the solvent
      control even in the presence of high PEEK concentrations (5.0 microg/ml).
      Therefore, in summary, the study produced no evidence of cell damage caused by
      PEEK.

PMID- 11950047
TI  - Micro X-ray diffraction study of superelastic nickel-titanium orthodontic wires
      at different temperatures and stresses.
AB  - The phase transformation behavior in three commercial nickel-titanium orthodontic
      wires having different transformation temperatures was studied by micro X-ray
      diffraction (micro-XRD). Micro-XRD spectra were obtained at three different
      included bending angles (135 degrees, 146 degrees and 157 degrees) and three
      different temperatures (25 degrees C, 37 degrees C and 60 degrees C). The regions
      analyzed by micro-XRD were within the separate areas of a given wire specimen
      that experienced only tensile or compressive strain. The intensity ratio
      (M002/A110) between the 002 peak for martensitic NiTi and the 110 peak for
      austenitic NiTi was employed as the index to the proportions of the martensite
      and austenite phases. The ratio of martensite to austenite increased in all three
      nickel-titanium wires with decreasing included bending angle (greater permanent
      bending deformation), and was lower within the compression area for all wires at
      all bending angles than within the tension area. Micro-XRD provides an effective
      method for quantitative evaluation of the proportions of these two phases in
      nickel-titanium orthodontic wires, even though considerable preferred
      crystallographic orientation exists because of the wire drawing process.

PMID- 11950046
TI  - Al-Cu-Fe quasicrystal/ultra-high molecular weight polyethylene composites as
      biomaterials for acetabular cup prosthetics.
AB  - Polymer composites of Al-Cu-Fe quasicrystals and ultra-high molecular weight
      polyethylene (UHMWPE) were investigated for use in acetabular cup prosthetics.
      The wear properties of the Al-Cu-Fe/UHMWPE samples and a 440 steel ball
      counterface were measured. The mechanical strength of the Al-Cu-Fe/UHMWPE
      composites was compared to UHMWPE and alumina/UHMWPE. The biocompatibility of the
      composite material was tested using a direct contact cytotoxicity assay. Al-Cu
      Fe/UHMWPE demonstrated lower volume loss after wear and higher mechanical
      strength than UHMWPE. This composite material also showed no increase in
      counterface wear or cytotoxicity relative to UHMWPE. These combined results
      demonstrate that Al-Cu-Fe/UHMWPE composites are promising candidate materials for
      acetabular cup prosthetics.

PMID- 11950048
TI  - Effect of biologically active coating on biocompatibility of Nitinol devices
      designed for the closure of intra-atrial communications.
AB  - Anti-thrombogenicity and rapid endothelialisation are prerequisites for the use
      of closure devices of intra-atrial communications in order to reduce the risk of
      cerebral embolism. The purpose of this study was therefore to assess the effect
      of bioactive coatings on biocompatibility of Nitinol coils designed for the
      closure of intra-atrial communications. Nitinol coils (n = 10, each) and flat
      Nitinol bands (n = 3, each) were treated by basic coating with poly(amino-p
      xylylene-co-p-xylylene) and then coated with either heparin, r-hirudin or
      fibronectin. Anti-thrombogenicity was studied in vitro in a dynamic model with
      whole blood by partial thromboplastin time (PTT), platelet binding and thrombin
      generation, respectively, and cytotoxicity by hemolysis. Endothelialisation was
      studied on Nitinol bands with human umbilical venous endothelial cells (HUVEC) by
      3-(4,5-dimethylthiazole-2yl)-2,5-triphenyl tetrazolium (MTT) assay and
      immnuofluorescence analysis of Ki67, vinculin, fibronectin and von Willebrand
      Factor. Uncoated or coated devices did not influence hemolysis and PTT. r-Hirudin
      (but not heparin) and fibronectin coating showed lower platelet binding than
      uncoated Nitinol (p < 0.005, respectively). Heparin and r-hirudin coating reduced
      thrombin formation (p < 0.05 versus Nitinol, respectively). HUVEC adhesion,
      proliferation, and matrix formation decreased in the order: fibronectin coating >
      uncoated Nitinol > r-hirudin coating > heparin coating > basic coating. MTT assay
      corroborated these findings. In conclusion, r-hirudin and fibronectin coating, by
      causing no acute cytotoxicity, decreasing thrombogenicity and increasing
      endothelialisation improve in vitro biocompatibility of Nitinol devices designed
      for the closure of intra-atrial communications.

PMID- 11950049
TI  - The influence of plasma proteins and platelets on oxygen radical production and F
      actin distribution in neutrophils adhering to polymer surfaces.
AB  - It is well known that blood cell interactions with artificial surfaces might have
      deleterious effects on host tissue, however, the mechanisms involved are far from
      understood. In this study, neutrophil-platelet interaction on uncoated or protein
      coated polymer surfaces was investigated. Cell spreading, reorganization of actin
      filaments and release of oxygen metabolites (measured as luminol-amplified
      chemiluminescence) were used as criteria for cell activation on positively
      charged, hydrophilic 1,2-diaminocyclohexane, and negatively charged, hydrophobic
      hexamethylene-disiloxane. The model surfaces were made by radio frequency plasma
      discharge polymerization. Neutrophil contact with the uncoated polymers induced a
      prolonged generation of oxygen radicals. Precoating of the polymer surfaces with
      human serum albumin (HSA) or fibrinogen, markedly reduced neutrophil activation,
      whereas coating with human immunoglobulin G (IgG), a well-known opsonin, resulted
      in significantly higher levels of cell activation. Consequently, protein coating
      overruled the activating effects of the polymer surfaces. The presence of
      unstimulated or thrombin-stimulated platelets markedly increased the reactivity
      of neutrophils against fibrinogen- and IgG-coated surfaces. However, neutrophils
      remained relatively unreactive in the presence of platelets on HSA-treated
      surfaces. Comparison of the different types of surfaces used, reveals a
      correlation between the degree of cell spreading, reorganization of the actin
      cytoskeleton and the amount of oxygen radicals produced. Our results suggest that
      the acute inflammatory reaction on a biomaterial surface is highly dependent on
      the nature and composition of the first adsorbed protein layer and the extent of
      platelet activation.

PMID- 11950050
TI  - Hydrogels based on poly(ethylene oxide) and poly(tetramethylene oxide) or
      poly(dimethyl siloxane): synthesis, characterization, in vitro protein adsorption
      and platelet adhesion.
AB  - In vitro protein adsorption, platelet adhesion and activation on new hydrogel
      surfaces, composed of poly(ethylene oxide) (PEO) and poly(tetramethylene oxide)
      (PTMO) or poly(dimethyl siloxane) (PDMS), were investigated. By varying PEO
      length (MW = 2000 or 3400), hydrophobic components (PTMO or PDMS) or polymer
      topology (block or graft copolymers), various physical hydrogels were produced.
      Their structures were verified by 1H NMR and ATR-IR and the molecular weights
      were determined by gel permeation chromatography. The hydrogels were soluble in a
      variety of organic solvents, while absorbed a significant amount of water with
      preserved three-dimensional structure by physical crosslinking. The dynamic
      contact angle measurement revealed that the surface hydrophilicity increased by
      incorporating longer PEO, PEO grafting, and adopting PDMS as a hydrophobic
      segment instead of PTMO. It was observed from in vitro protein adsorption study
      that the hydrogels exhibited significantly lower adsorption of human serum
      albumin (HSA), human fibrinogen (HFg), and IgG, when compared with Pellethane, a
      commercial polyurethane taken as a control. The hydrogels were attractive for HSA
      but not sensitive to HFg and IgG. And more than 65% of the proteins detected on
      the surfaces of the hydrogels were reversibly detached by being treated with an
      SDS solution. It was evident that the hydrogels synthesized in this study were
      much more resistant to platelet adhesion than the control, which might depend on
      the composition of proteins adsorbed on the surfaces and their degree of
      denaturation. Among the hydrogels tested, PEO3,4kPDMS exhibited albumin-rich and
      platelet-resistant surfaces, implying a potential candidate for biomaterial.

PMID- 11950051
TI  - Qualitative and quantitative observations of bone tissue reactions to anodised
      implants.
AB  - Research projects focusing on biomaterials related factors; the bulk implant
      material, the macro-design of the implant and the microsurface roughness are
      routinely being conducted at our laboratories. In this study, we have
      investigated the bone tissue reactions to turned commercially pure (c.p.)
      titanium implants with various thicknesses of the oxide films after 6 weeks of
      insertion in rabbit bone. The control c.p. titanium implants had an oxide
      thickness of 17-200 nm while the test implants revealed an oxide thickness
      between 600 and 1000 nm. Routine histological investigations of the tissue
      reactions around the implants and enzyme histochemical detections of alkaline and
      acid phosphatase activities demonstrated similar findings around both the control
      and test implants. In general, the histomorphometrical parameters (bone to
      implant contact and newly formed bone) revealed significant quantitative
      differences between the control and test implants. The test implants demonstrated
      a greater bone response histomorphometrically than control implants and the
      osteoconductivity was more pronounced around the test implant surfaces. The
      parameters that differed between the implant surfaces, i.e. the oxide thickness,
      the pore size distribution, the porosity and the crystallinity of the surface
      oxides may represent factors that have an influence on the histomorphometrical
      results indicated by a stronger bone tissue response to the test implant
      surfaces, with an oxide thickness of more than 600 nm.

PMID- 11950052
TI  - Effect of chemical structure on degree of conversion in light-cured
      dimethacrylate-based dental resins.
AB  - In this work the room-temperature photopolymerization of Bis-GMA, Bis-EMA,
      urethane dimethacrylate (UDMA) and triethylene glycol dimethacrylate (TEGDMA)
      induced by camphoroquinone/N,N-dimethylaminoethyl methacrylate, as photo
      initiator system, was followed by FT-IR. The results obtained were then fitted by
      a non-linear least square method to a rational function, which permitted the
      accurate calculation of the limiting degree of conversion. The latter was found
      to increase in the order Bis-GMA < Bis-EMA < UDMA < TEGDMA. This trend is
      discussed in connection with the chemical structure of dimethacrylates. The
      photopolymerization of mixtures of Bis-GMA/TEGDMA, Bis-GMA/UDMA and Bis-GMA/Bis
      EMA showed a good linear relationship of degree of conversion with the mole
      fraction of Bis-GMA and in the case of the first pair also with the Tg of the
      initial monomer mixture.

PMID- 11950053
TI  - Influence of neutron irradiation on holmium acetylacetonate loaded poly(L-lactic
      acid) microspheres.
AB  - Holmium-loaded microspheres are useful systems in radio-embolization therapy of
      liver metastases. For administration to a patient, the holmium-loaded
      microspheres have to be irradiated in a nuclear reactor to become radioactive. In
      this paper. the influence of neutron irradiation on poly(L-lactic acid) (PLLA)
      microspheres and films, with or without holmium acetylacetonate (HoAcAc), is
      investigated, in particular using differential scanning calorimetry (MDSC),
      scanning electron microscopy, gel permeation chromatography (GPC), infrared
      spectroscopy, and X-ray diffraction. After irradiation of the microspheres, only
      minor surface changes were seen using scanning electron microscopy, and the
      holmium complex remained immobilized in the polymer matrix as reflected by a
      relatively small release of this complex. GPC and MDSC measurements showed a
      decrease in molecular weight and crystallinity of the PLLA, respectively, which
      can be ascribed to radiation induced chain scission. Irradiation of the HoAcAc
      loaded PLLA matrices resulted in evaporation of the non-coordinated and one
      coordinated water molecule of the HoAcAc complex, as evidenced by MDSC and X-ray
      diffraction analysis. Infrared spectroscopy indicated that some degradation of
      the acetylacetonate anion occurred after irradiation. Although some radiation
      induced damage of both the PLLA matrix and the embedded HoAcAc-complex occurs,
      the microspheres retain their favourable properties (no marginal release of Ho,
      preservation of the microsphere size), which make these systems interesting
      candidates for the treatment of tumours by radio-embolization.

PMID- 11950054
TI  - Fibronectin peptides mediate HMEC adhesion to porcine-derived extracellular
      matrix.
AB  - Extracellular matrices (ECM) derived from porcine tissues have been shown to
      support the successful repair and remodeling of injured tissues when evaluated in
      animal models. Cell-matrix interactions, including ligand-integrin associations
      that facilitate endothelial cell adhesion, are clearly important in the tissue
      remodeling process. The goal of the present study was to identify the peptide
      sequences within the ubiquitous protein fibronectin (FN) that may be important in
      the initial interactions between the host endothelial cells and the ECM scaffold.
      Human microvascular endothelial cells (HMEC) were seeded upon porcine ECM after
      having been subjected to pretreatment with peptide ligands derived from tissue FN
      and were allowed to attach for 20 min. Non-adherent cells were removed and the
      remaining, tritium-labeled cells attached to the ECM were counted. Results showed
      that cyclo-RGD and REDV, but not LDV or PHSRN, play a role in mediating the
      attachment of HMEC to porcine ECM.

PMID- 11950055
TI  - Alpha-tricalcium phosphate hydrolysis to octacalcium phosphate: effect of sodium
      polyacrylate.
AB  - Alpha-Tricalcium phosphate (alpha-TCP) hydrolysis into octacalcium phosphate
      (OCP) has been investigated in phosphoric acid solution at different
      concentrations of sodium polyacrylate (NaPA). The hydrolysis process has been
      followed by powder X-ray diffraction, infrared absorption and scanning electron
      microscopy analyses. In the absence of the polyelectrolyte, alpha-TCP undergoes a
      complete transformation into OCP in 24 h. The presence of polyacrylate in
      solution inhibits the hydrolysis so that a NaPA concentration of 0.5 microm is
      sufficient to lengthen the time required to complete the hydrolysis to 4 days.
      The variation of Ca2+ concentration in the soaking solution suggests that the
      transformation occurs through alpha-TCP dissolution followed by OCP
      precipitation. The delayed OCP nucleation and growth in the presence of
      polyacrylate implies a preferential adsorption of the polyelectrolyte on the
      growing OCP crystals, which induces an anisotropic reduction of the coherence
      lengths of the perfect crystalline domains.

PMID- 11950056
TI  - Ceramic and PMMA particles differentially affect osteoblast phenotype.
AB  - There is increasing evidence that wear debris particles present in periprosthetic
      tissues have direct effects on osteoblasts. The nature of the cell response
      varies with the chemistry of the particle and the number of particles. Most
      studies have used Ti, Ti-6Al-4V, and ultrahigh molecular weight polyethylene
      (UHMWPE) particles since these materials are most frequently used in implants and
      as a result, these particles predominate in peri-prosthetic tissues. Ceramics
      have also been used successfully as load-bearing surfaces in implants for years,
      although it is unknown how wear debris from these surfaces may contribute to
      aseptic bone loss. Further, particles resulting from polymethylmethacrylate
      (PMMA) cements used for fixation may also be involved in aseptic loosening of
      implants, but how these particles may affect bone formation is unknown. In the
      present study, we examined whether aluminum oxide (Al2O3), zirconium oxide
      (ZrO2), and PMMA particles exert effects on osteoblast proliferation, phenotypic
      expression, and local factor production, and if so, whether the effects were
      specific to the particle type. ZrO2 particles were produced in a custom-made
      axial mixer in which ZrO2 containers were filled with ZrO2 bars and 95% ethanol
      and then rotated continuously at room temperature. PMMA particles were prepared
      in a ZrO2 roller mill. Al2O3 was produced and provided by Aesculap AG. Particles
      were endotoxin-free with equivalent circle diameters <3 microm; Al2O3 particles
      were significantly smaller than ZrO2 or PMMA particles. Particle suspensions were
      added to confluent cultures of MG63 osteoblast-like cells after diluting them
      1:100, 1:10, and 1:1 with culture medium. Cells were incubated with the particles
      for 24 h. Transmission electron microscopy showed that MG63 cells phagocytosed
      Al2O3 particles and exhibited ultrastructural changes consistent with
      cytotoxicity. This was supported by biochemical changes as well. Proliferation,
      alkaline phosphatase activity, and TGF-beta1 levels were decreased. ZrO2 and PMMA
      particles increased proliferation and alkaline phosphatase specific activity. The
      effect of ZrO2 on alkaline phosphatase was targeted to matrix vesicles, the
      effect of PMMA was greater on the cells. All particles increased prostaglandin E2
      production. These results show that Al2O3, ZrO2, and PMMA particles elicit direct
      effects on osteoblasts and that cell response depends on the particle type. None
      of the particles tested had the same effect as noted previously for UHMWPE:
      increased proliferation and decreased alkaline phosphatase. These results may
      indicate that the response of peri-prosthetic tissues to wear particles may be
      modulated by the relative contributions of the various particle types present.

PMID- 11950057
TI  - Preparation and in vitro bioactivity of hydroxyapatite/solgel glass biphasic
      material.
AB  - Hydroxyapatite/solgel glass biphasic material has been obtained in order to
      improve the bioactivity of the hydroxyapatite (OHAp). A mixture of stoichiometric
      OHAp and the precursor gel of a solgel glass, with nominal composition in mol%
      CaO-26, SiO2-70, P205-4, has been prepared. The amounts of components used have
      been selected to obtain a final relationship for OHAp/solgel glass of 60/40 on
      heating. Two different thermal treatments have been used: (i) 700 degrees C,
      temperature of solgel glass stabilisation and (ii) 1000 degrees C, lower
      temperature of hydroxyapatite sintering. The bioactivity of the resulting
      materials has been examined in vitro by immersion in simulated body fluid at 37
      degrees C. The results obtained show that both materials are bioactive. The
      apatite-like layer grown is greater for the new materials than for the OHAp and
      the solgel glass themselves.

PMID- 11950058
TI  - Mechanical performance of acrylic bone cements containing different
      radiopacifying agents.
AB  - The effect that three different radiopacifying agents, two of them inorganic
      (BaSO4, ZrO2) and one organic (an iodine containing monomer, IHQM) have on the
      static and dynamic mechanical properties of acrylic bone cements was studied.
      Compressive and tensile strength, fracture toughness and fatigue crack
      propagation were evaluated. The effect of the inorganic fillers depends on their
      size and morphology. In relation to the radiolucent cement, the addition of
      zirconium dioxide improved significantly the tensile strength, the fracture
      toughness and the fatigue crack propagation resistance. In contrast, the addition
      of barium sulphate produced a decrease of the tensile strength, but did not
      affect the fracture toughness and improved the crack propagation resistance. When
      the iodine containing monomer was used, although the tensile strength and the
      fracture toughness increased, the fatigue crack propagation resistance remained
      as low as it was for the radiolucent cement.

PMID- 11950059
TI  - New partially degradable and bioactive acrylic bone cements based on starch
      blends and ceramic fillers.
AB  - This work reports the development of new partially biodegradable acrylic bone
      cements based on corn starch/cellulose acetate blends (SCA), prepared by the free
      radical polymerization of methyl methacrylate and acrylic acid at low
      temperature. Amounts of biocompatible, osteoconductive and osteophilic mineral
      component such as hydroxylapatite (sintered and non-sintered), were incorporated
      in different percentages to confer a bone-bonding character to the bone cements
      in this type of applications. All cement formulations were characterized by 1H
      NMR spectroscopy. Curing parameters and mechanical properties were determined
      finding formulations which complete the ASTM legislation. Hydration degree,
      degradation studies, as well as bioactivity tests were performed in all prepared
      formulations. The developed systems show a range of properties that might allow
      for their application as self-curing bone cements, exhibiting several advantages
      with respect to other commercially available bone cements.

PMID- 11950060
TI  - Water absorption characteristics of dental composites incorporating
      hydroxyapatite filler.
AB  - Water uptake characteristics of BisGMA-based composites incorporating untreated
      and surface-treated hydroxyapatite (HA) with a silane coupling agent have been
      investigated. The water absorption and desorption behaviour of these composites
      obeyed the classical diffusion theory. The diffusion coefficients of the
      composites during first absorption were very similar to that for the base resin,
      suggesting that the water uptake process occur mainly in the resin matrix. The
      incorporation of HA reduced the water uptake of the base resin and lower uptake
      was found for those formulated with surface-treated HA. It was also observed that
      the equilibrium uptake decreased with increasing filler loading. However, the
      filled specimens had a higher water absorption than which would be expected on
      the basis of the resin content. This increase in the water uptake was largely due
      to the presence of porosity and filler particle aggregates in the microstructure
      of composites, although the adsorption of some water onto the filler surface has
      not been ruled out. The experimental composites showed higher solubilities than
      that obtained for the base resin.

PMID- 11950061
TI  - Analysis of novel and recurrent mutations responsible for the tricho-rhino
      phalangeal syndromes.
AB  - The tricho-rhino-phalangeal syndromes (TRPS type I, II, and III) are autosomal
      dominant disorders sharing the following characteristics: slowly growing and
      sparse scalp hair, medially thick and laterally thin eyebrows, bulbous tip of the
      nose, long flat philtrum, thin upper lip with vermilion border, and protruding
      ears. In addition, individuals with TRPS generally share skeletal and bone
      anomalies, including shortening of the phalanges and metacarpals (mild to severe
      brachydactyly), cone-shaped epiphyses, hip dysplasia, and short stature. The
      etiology of the different types of TRPS can result from either single base pair
      mutations, or the complete deletion of the TRPS1 gene, which encodes a zinc
      finger transcription factor located on chromosomal band 8q24.1. We have
      identified nine heterozygous mutations, five novel and four recurrent, in
      unrelated families diagnosed with TRPS. The five novel mutations identified show
      1- or 2-bp deletions and a single base substitution, whereas all of the recurrent
      mutations are single base substitutions. Seven of the nine mutations result in a
      premature stop codon, leading to a truncated, nonfunctional TRPS1 protein. The
      final two mutations are missense mutations in the GATA DNA binding zinc finger,
      which is believed to be important for the protein's normal function.

PMID- 11950062
TI  - Impaired interactions between mouse Eyal harboring mutations found in patients
      with branchio-oto-renal syndrome and Six, Dach, and G proteins.
AB  - Mutations in the EYA1 gene are responsible for branchio-oto-renal (BOR) syndrome
      as well as for other ocular defects. Most of the mutations are located within or
      in the vicinity of the EYA domain, which is highly conserved in the EYA protein
      family. The EYA domain is required for protein-protein interactions, which are
      important to the biological function of EYA proteins. To determine how EYA1
      mutations cause BOR syndrome and/or ocular defects, we tested the effects of Eya1
      mutations on interactions with Six. Dach, and G proteins by mammalian two-hybrid
      and GST-pulldown assays. Defective interactions were noted between BOR-type
      mutations S486P and L504R of Eya1 and Dach1, G proteins, and some Six proteins.
      These mutations impaired the activation of transcription from a Six-responsive
      gene, myogenin, with Six5. S486P and L504R showed an altered digestion pattern
      with trypsin, and L504R also decreased the sensitivity to V8 protease digestion
      and produced a peptide fragment with a different M(r). Our results suggest that
      defective protein-protein interactions of the mutations in the EYA domain
      underlie BOR syndrome and that SIX, DACH, and/or G proteins are possibly involved
      in the pathogenic processes.

PMID- 11950063
TI  - Anthropological implication of the SDF1-3'A allele distribution in Southeast Asia
      and Melanesia.
AB  - The distribution of the SDF1-3'A allele among 1848 individuals in Southeast Asia
      and Melanesia was studied with the polymerase chain reaction-restriction fragment
      length polymorphism assay. The SDF1-3'A allele frequency in the populations of
      mainland Southeast Asia ranged from 0.0 to 0.355, whereas in the populations of
      insular Southeast Asia and Melanesia, it ranged from 0.233 to 0.733, with an
      increasing cline from west to east. Correlation between SDF1-3'A frequency and
      longitude values was highly significant for the populations in the Pacific region
      (r = 0.867, P < 0.001). The geographic distribution of the SDF1-3'A frequencies
      in the Pacific region was interpreted by an admixture of Austronesians with the
      aboriginal people in situ. In addition, this study found high proportions of SDF1
      3'A/3'A homozygous individuals in several populations, which will enable us to
      evaluate roles of the SDF1 genotypes in SDF-1 expression.

PMID- 11950064
TI  - Evidence for the de novo regeneration of the pattern of the length heteroplasmy
      associated with the T16189C variant in the control (D-loop) region of
      mitochondrial DNA.
AB  - We have investigated the genetics of the length heteroplasmy associated with the
      T16189C variant of mitochondrial DNA (mtDNA), and report here definitive evidence
      that the pattern of the length heteroplasmy is not simply the outcome of drift
      related to the random segregation of the mtDNA population during cell division,
      but is actively maintained and regenerated de novo following each cell division.
      The pattern of the length heteroplasmy was maintained in a fibroblast cell line
      during an extensive mtDNA depletion experiment by ethidium bromide treatment, and
      following the subsequent repopulation of the cells with mtDNA. The investigation
      of the pattern of the length heteroplasmy by single cell pick up shows a similar
      pattern in sister cells despite the evidence of the randomness of mtDNA
      segregation, providing definitive evidence for the de novo regeneration of the
      pattern following cell division. Consistent with this conclusion is the
      observation that similar patterns of length heteroplasmy are found in tissues of
      single individuals.

PMID- 11950065
TI  - Association analysis of nine missense polymorphisms in the coagulation factor V
      gene with severe preeclampsia in pregnant Japanese women.
AB  - The Leiden mutation in the coagulation factor V (F5) gene associated with
      preeclampsia in Caucasians has not been found in Japanese populations. We
      examined the association of 20 missense polymorphisms in the F5 gene in 133
      pregnant Japanese women with preeclampsia and in 224 unrelated, healthy, pregnant
      Japanese women. Among nine polymorphisms identified in the subjects, the M385T
      and R485K polymorphisms were associated with preeclampsia (P = 0.05 and P = 0.02,
      respectively). Haplotype analysis indicated that the R485K polymorphism is truly
      associated with preeclampsia, whereas the association of the M385T polymorphism
      is due to linkage disequilibrium. Taken together with reports that the R485
      allele yields poor factor V function in comparison with that of the K485 allele
      and that the F5 Leiden mutation is associated with preeclampsia in Caucasian
      populations, the findings of the present study suggest that the F5 gene is
      associated with preeclampsia in pregnant Japanese women.

PMID- 11950066
TI  - Ethnic divergence and linkage disequilibrium of novel SNPs in the human NLI-IF
      gene: evidence of human origin and lack of association with tuberculosis
      susceptibility.
AB  - Sequence variation in the human genome has been used as a tool in studying human
      diseases and the evolutionary history of man. A human inherited predisposition to
      tuberculosis has been suggested and studied; however. genetic mechanisms are
      still ambiguous. In the present study, we scanned the regulatory and coding
      region of Nuclear LIM Interactor-Interacting Factor gene (NLI-IF), which is
      physically close to the tuberculosis-associated gene NRAMP1. Thirteen biallelic
      single-nucleotide polymorphisms (SNPs) were identified from four ethnic
      populations (African-American, Caucasian, Hispanic, and Asian) with population
      specific distribution of alleles. The extent of linkage disequilibrium (LD)
      between 402T > C, and 472-42G > A varied distinctly from complete LD in the non
      African-American groups to strong but incomplete LD in African-Americans. Both
      SNPs were in significant LD with the polymorphism 3' UTR in NRAMP1 among these
      ethnic groups (P < 0.02), except 402T > C in African-Americans. In a case-control
      study with a Caucasian population, three cosmopolitan SNPs (204C > A, 402T > C
      and 472 - 42G > A) in NLI-IF showed no significant association with human
      susceptibility to tuberculosis. Our results support the "out-of-Africa" model of
      human origin, and suggest the time for the common ancestor dispersing from Africa
      could not have been more than approximately 385,620 years ago.

PMID- 11950067
TI  - Theoretical analysis and experimental verification of ozone mass transfer in
      bubble columns.
AB  - Modeling the performance of ozone bubble columns for water and wastewater
      treatment was carried out using two models: the axial dispersion model and the
      back flow cell model (BFCM). Expressing these two models in terms of
      dimensionless operating parameters allowed the examination of their predictions
      of dissolved ozone, gaseous ozone, and superficial gas velocity profiles along
      the bubble column height. Pilot-scale experimental data from the literature were
      used to test the models' predictions of the dissolved ozone profiles for water
      treatment applications. The models have demonstrated reliable predictions of the
      dissolved ozone concentration profiles along the bubble column for water
      treatment conditions in the co-current and the counter-current flow modes. The
      axial dispersion model and the back flow cell model have proved to be adequate
      for describing the performance of ozone bubble columns, however, the BFCM was
      easier to formulate and solve.

PMID- 11950068
TI  - Impact of hydrogen peroxide oxygen transfer tests on the performance of the
      biological nutrient removal process.
AB  - Knowledge of in-process oxygen transfer is essential to the optimum design and
      operation of aeration systems in activated sludge processes. In this study, non
      steady state H2O2 oxygen transfer tests were performed in a laboratory scale,
      University of Cape Town configuration biological nutrient removal process (BNR)
      to measure the in-process oxygen transfer rates. Given the small quantity (about
      1 ml @30% concentration) of H2O2 used in the aerobic reactor with a mixed liquor
      volume of 161 (total system working volume of 33.65 l), no effect on the process
      performance itself was expected. However, the process performance data obtained
      indicated results to the contrary. Use of H2O2 in measuring process oxygen
      transfer rates may not be suitable for BNR processes, as all the major process
      performance indicators (carbon, nitrogen and phosphorus removal by the system and
      carbon uptake and phosphorus release in the anaerobic zone) were negatively
      affected. Evidence in thiswork leads to the conclusion that external addition of
      H2O2 leads to excessive production of the hydroxyl radical. Since microorganisms
      do not have enzyme systems capable of acting upon this additional reactive
      radical, it resulted in loss of process performance. It is also possible that
      H2O2 could have upset the normal aerobic respiration process by introducing
      oxidative stress conditions on the catalase, peroxidase and superoxide dismutase
      enzymes that deal with other oxygen radicals generated as part of the overall
      process of reducing oxygen to water. Any test that interferes with the system in
      which the test is being performed is suspect. Therefore, in light of these
      results, the H2O2 method to test in-process oxygen transfer should be re
      evaluated.

PMID- 11950069
TI  - A new approach to modelling substrate inhibition.
AB  - Substrate inhibition, which is one of the most frequently observed phenomena in
      the biological treatment of industrial wastewaters, has been the subject of
      numerous studies. Yet there are still cases which cannot be adequately described
      by the existing models. In this paper, a review of substrate inhibition
      approaches was made. A new model is proposed that assumes a common mechanism for
      substrate and product inhibition. The model is a continuous function having a
      maximum growth rate at the critical substrate concentration, beyond which the
      growth rate decreases as the substrate concentration is increased. The model also
      predicts the maximum substrate concentration where the growth ceases. The model
      was tested using existing data in the literature to assess the model response and
      predictability of critical points. The literature datahave been selected from the
      studies conducted on pure and mixed cultures in batch and continuous reactors for
      phenol and several phenolics as well as from the studies which employed the
      Haldane model. A curve fitting method was used to determine the model parameters.
      The fit of the model to the data was satisfactory, particularly for the substrate
      concentrations exceeding maximum growth rate.

PMID- 11950070
TI  - Photocatalytic degradation of p-coumaric acid over TiO2 suspensions.
AB  - The photocatalytic degradation of p-coumaric acid, a biorecalcitrant phenolic
      compound typically found in olive processing and wine distillery waste waters,
      has been investigated in aqueous heterogeneous solutions containing semiconductor
      powders as photocatalysts. The disappearance of the organic molecule follows
      approximately a pseudo-first kinetic order according to the Langmuir-Hinselwood
      model. The most important reaction intermediates were determined by GS-MS and
      HPLC measurements, suggesting a reaction pathway for the photodegradation.
      Various commercial photocatalysts were compared with respect to their overall
      efficiency, as well as the production of CO2. The effect of H2O2 on the reaction
      rate was ascertained.

PMID- 11950071
TI  - Comparison of the effect of surface application and subsurface incorporation of
      enhanced treated biosolids on the leaching of heavy metals and nutrients through
      sand and sandy loam soils.
AB  - Use of enhanced treated biosolids such as composted and dried, mesophilic
      anaerobically digested, dewatered (MADD) biosolids is becoming more popular. This
      is mainly in response to concerns over the potential for pathogens to enter the
      food chain. There is, therefore, a need to investigate how enhanced treatment,
      and methods by which these biosolids are applied, affects the leaching potential
      of metal and nutrients to ensure that water quality is not compromised. MADD cake
      (fresh, dried and composted) and MAD liquid sludge were applied by surface
      application and subsurface incorporation to sand (typic quartzipsamments, %OM =
      3.0, pH = 6.5), sandy loam (typic hapludalf, %OM = 4.8, pH = 7.6) and silversand
      'repacked semi-structured cores' (0.2 m by 0.1 m diameter) at rates equivalent to
      250 kg N ha(-1) yr(-1). Leaching of Zn, Cu, Pb, Ni, N and P was investigated
      following application of five 8 h simulated rainfall events (4.9 mm h(-1)) in the
      laboratory. Little difference was observed between leaching of metals and
      nutrients from soils amended with enhanced treated biosolids (dried and composted
      MADD cakes) compared with conventional biosolids (fresh MADD cake and MAD
      liquid). Subsurface incorporation increased the risk of P and metal leaching
      compared with surface application. Nitrate losses were independent of application
      method. Similar nutrient losses from control and amended cores indicated that the
      leaching was derived predominantly from the soil clay and organic matter
      complexes. Evidence for attenuation of biosolids-derived metals and P by soil
      derived clay and/or organic matter was found. Water balance data showed that
      hydrological regimes of each core were comparable and unlikely to account for
      observed differences in leaching losses.

PMID- 11950072
TI  - Biodegradation of the organochlorine pesticide, lindane by a sub-tropical white
      rot fungus in batch and packed bed bioreactor systems.
AB  - The degradation of the organochlorine pesticide, lindane by a sub-tropical white
      rot fungus DSPM95 was studied in stationary batch and packed bed bioreactor
      systems. Pesticide concentrations of 5, 10, 20 and 40 ppm were used in batch
      cultures while concentrations of 1, 2, 5 and 10 ppm were used in the packed bed
      bioreactor. Biodegradation of 82 +/- 6% was achieved in batch cultures at
      concentrations of 5 and 10 ppm. The highest percent degradation achieved in the
      packed bed reactor was 81% at lindane concentrations of 1 and 2 ppm and the
      degradation decreased at 10 ppm. The amount of lindane degraded was directly
      proportional to the initial lindane concentration in the medium. Laccase and
      manganese peroxidase were produced in both stationary batch and in immobilised
      cultures, however high enzyme levels could not be sustained for long periods in
      the packed bed bioreactor.

PMID- 11950073
TI  - The effect of carbonate on the precipitation of calcium phosphate.
AB  - In order to facilitate the recovery of phosphorus from wastewater, the effect of
      carbonate on the precipitation of calcium phosphate has been studied. The effect
      of carbonate concentrations up to 5.00 millimoles per liter on the precipitation
      of 20 milligrammes phosphorus per liter phosphate was studied. At pH 8.00 the
      precipitation rate of phosphate was greatly retarded by carbonate and the
      corresponding precipitation efficiency also decreased, but at pH values > or =
      9.00 the effect of carbonate on the precipitation of phosphate was very small.
      This indicates that carbonate may decrease the precipitation rate and efficiency
      of calcium phosphate, but the solution pH value is still a key factor influencing
      the precipitation process. The effect of carbonate on the precipitation of
      phosphate was attributed to the formation of ion pairs between carbonate and
      calcium and the decrease of free calcium ions. This resulted in the decrease of
      the thermodynamic driving force for the precipitation of calcium phosphate, so
      the effect of carbonate on the precipitation of phosphate was in fact a competing
      one, although this competing effect was not so obvious at pH > or = 9.00.
      Carbonate may be coprecipitated with phosphate from solution, especially at pH
      9.00-11.00, and this will decrease the relative phosphorus content of the
      precipitate. The increases in solution pH value and initial Ca/P ratio are two
      approaches to overcome the influence of carbonate on the precipitation of
      phosphate, but the solution pH values should be lower than 10.00 and the initial
      Ca/P ratios should not exceed 5.00.

PMID- 11950074
TI  - Vortex-enhanced capture of airborne particulates.
AB  - The study reported here sought to exploit aeroelastically-generated vortices for
      enhanced capture of airborne particles by horizontal, flat plate collectors.
      Elastically-supported bluff bodies of different cross-sections were screened for
      suitable plunge (transverse) oscillation at air velocities ranging from about 1
      to 10 m s(-1). Both "D" shapes and trapezoidal prisms proved to be particularly
      effective; the "D" provided an increase in particle capture of 64% relative to
      the undisturbed flow over a flat plate at a mean air speed of 1.5 m s(-1). At
      higher velocities, a "T" shaped cross-section (producing mainly torsional
      oscillation) was found to be extremely effective at increasing capture for
      airborne particles with a mean diameter of 8 microm. Dynamic pressure
      measurements made downstream from the oscillators revealed that the torsional
      oscillation of the "T" produced a flow with multiple periodicities, whereas the
      plunge oscillators produced a wake that was more sharply periodic. These results
      indicate that aeroelastically intensified vortices, generated at Reynolds numbers
      ranging from about 2300 to 5200, can significantly improve particle removal from
      air streams. Furthermore, the effect can be exploited in both internal (duct) and
      external (free) flows.

PMID- 11950076
TI  - Residential school nursing.

PMID- 11950075
TI  - Co-processing of organic fraction of municipal solid waste and primary sludge-
      stabilization and disinfection.
AB  - Batch mesophilic digesters were fed a mixture of the organic fraction of
      municipal solid waste (OF-MSW) and primary sludge (PS), and operated under non
      mixing condition at a 30-day influent mass retention time. The reactors were
      started in a slurry mode and brought to the target level of 26-30% total solids
      in about 3 months from start. Two feed characteristics, the level of PS solids in
      the feed, and the particle size of the OF-MSW, were the variables used to
      determine their effect on methane production during digester operation. Higher
      biodegradable volatile solid reductions and methane yields matched increased
      fractions of primary sludge in the feed (5%, 10%, and 15% as dry solids).
      Incomplete digestion, limited to fermentation, took place in reactors that did
      not receive primary sludge. The particle size did not have any effect on specific
      weight of the feed but the amount of primary sludge did. Addition of vitamins and
      micronutrients to the inhibited reactors did not stimulate methane production,
      which narrowed the range of possible causes to the lack of available
      macronutrients, namely nitrogen. On the other hand, possible un-ionized ammonia
      (NH3) inhibition of reactors fed with the highest primary sludge-amended feed
      hindered organic conversion rates. Elimination of pathogenic microorganisms from
      the high-solids residue via long-term storage, followed by low-dose lime
      disinfection, was also investigated. Storage alone reduced fecal coliform and
      Salmonella sp. bacteria to below detection, but bacterial spores of anaerobic
      Clostridium perfringens survived. Subsequent liming of the residue caused
      irreversible inactivation of the spores because of high pH and, possibly, free
      ammonia (NH3) inherent to sludge.

PMID- 11950077
TI  - What would you do? School nurse consultants: Q & A.

PMID- 11950078
TI  - The healthy female heart.

PMID- 11950079
TI  - Legislative action: advocating the need for a school nurse.

PMID- 11950080
TI  - Player with heart.

PMID- 11950081
TI  - Brain research: have you heard the buzz?

PMID- 11950082
TI  - Health fair planning guide.

PMID- 11950083
TI  - Asthma in school children: it's important to re recognize the seriousness of this
      disease.

PMID- 11950084
TI  - A laser flash photolysis study of fenofibric acid in aqueous buffered media:
      unexpected triplet state inversion in a derivative of 4-alkoxybenzophenone.
AB  - Laser excitation of aqueous solutions of fenofibric acid (FA) at pH 7.4 show the
      formation of two reaction intermediates, the triplet state and the hydrated
      electron. The former is longer lived in water than in acetonitrile; its anionic
      form decays irreversibly by decarboxylation to give a carbanion that protonates
      before or after rearrangement. Several spectroscopic and quenching studies
      suggest that in aqueous media the triplet state of FA has a pi,pi* character, in
      comparison with an n,pi* character in organic media. Further, the known chemistry
      of the triplet, including decarboxylation and hydrogen abstraction, occurs
      predominantly from the n,pi* state, and as a consequence, activation energies are
      higher when the lowest triplet has a pi,pi* character. Photoionization is more
      important in aqueous than in organic media and involves a biphotonic process.
      Hydrated electrons are trapped by FA, leading to the corresponding ketyl radical
      after protonation.

PMID- 11950085
TI  - Fluorescent properties of oligonucleotide-conjugated thiazole orange probes.
AB  - The fluorescence properties of thiazole orange, linked via a (1) hydrophobic
      alkyl or a (2) hydrophilic ethylene glycol chain to the central internucleotidic
      phosphate group of a pentadeca-2'-deoxyriboadenylate (dA15), are evaluated.
      Linkage at the phosphate group yields two stereoisomers, S-isomer of the
      phosphorus chiral center (Sp) and R-isomer of the phosphorus chiral center (Rp);
      these are studied separately. The character of the linkage chain and the
      chirality of the internucleotidic phosphate linkage site influence the
      fluorescent properties of these thiazole orange-oligonucleotide conjugates (TO
      probes). Quantum yields of fluorescence (phifl) of between 0.04 and 0.07 were
      determined for the single-stranded conjugates. The fluorescence yield increased
      by up to five times upon hybridization with the complementary sequence
      (d5'[CACT15CAC3']); (phifl values of between 0.06-0.35 were determined for the
      double-stranded conjugates. The phifl value (0.17) of thiazole orange, 1-(N,N'
      trimethylaminopropyl)-4-[3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene]
      quinolinium iodide (TO-Pro 1) in the presence of the oligonucleotide duplex (TO
      Pro 1: dA15.d5'[CACT15CAC3'] (1:1)) is much less than that for some of the
      hybrids of the conjugates. Our studies, using steady-state and time-resolved
      fluorescence experiments, show that a number of discrete fluorescent association
      species between the thiazole orange and the helix are formed. Time-resolved
      studies on the four double-stranded TO-probes revealed that the fluorescent
      oligonucleotide-thiazole orange complexes are common, only the distribution of
      the species varies with the character of the chain and the chirality at the
      internucleotidic phosphate site. Those TO-probes in which the isomeric structure
      of the phosphate-chain linkage is Rp, and therefore such that the fluorophore is
      directed toward the minor groove, have higher phifl values than the Sp isomer. Of
      the systems studied, thiazole orange linked by an alkyl chain to the
      internucleotidic phosphate (Rp isomer) has the highest phifl and the greatest
      fraction of the longest-lived fluorescent thiazole orange species (in the hybrid
      form).

PMID- 11950086
TI  - Kinetic analysis of a photosensitive chelator and its complex with Zn(II).
AB  - The reversible sequestration and release of metal ions is an important objective
      in biological and environmental research. Unfortunately, although there have been
      dramatic examples of metal ion activity control, there are very few quantitative
      investigations of stoichiometry, equilibria and kinetics. A significant
      contributor to this lack of quantitative work is the complexity of many
      photochromic systems. Therefore, we have attempted to create a simple, reversible
      photochromic metal-ion chelator that can be analyzed quantitatively. The chelator
      should have certain other attributes as well, namely, that it binds to divalent
      metal ions (because of their extreme biological importance) and that it binds
      metal ions in the dark so that light is used to release metal ions rather than
      sequester them. The photochromic chelator (1) binds to divalent metal ions
      [Zn(II), Cu(II), Pb(II), Hg(II), Fe(II), Co(II) and Cd(II); other metal ions have
      not yet been tested] in the dark with a significant binding strength. In both
      methanol (by spectrophotometry) and methanol-water (by voltammetry), the
      stoichiometry of the 1-Zn(II) complex is 2:1. The binding constant (K1K2) is on
      the order of 10(12)-10(14) M(-2) in methanol and 5.0 x 10(8) M(-2) in 50% aqueous
      methanol. The chelator 1 is photolabile, yielding 2 with a quantum efficiency of
      0.91. In a solution containing excess Zn(II), so that over 99% of the ligand
      exists as the monodentate complex, photolysis produces 2 with a quantum
      efficiency of 0.15. A kinetic analysis leads to the conclusion that the complex
      itself is photolabile.

PMID- 11950087
TI  - Reverse intersystem crossing in rose bengal. II. Fluence dependence of
      fluorescence following 532 nm laser excitation.
AB  - A fluence-dependent fluorescence technique was used to observe reverse
      intersystem crossing from a certain higher-lying triplet state of rose bengal
      populated by a single pulse of 532 nm light. The quantum yield of reverse
      intersystem crossing from this state was determined to be 0.12+/-0.02 for rose
      bengal in phosphate-buffered saline. The importance of including molecular
      rotation effects in the analysis of fluorescence resulting from reverse
      intersystem crossing is discussed. Differences in the photochemical reactivity of
      upper triplet states in biological systems have been previously hypothesized to
      result from photophysical differences, particularly substantial differences in
      their reverse intersystem crossing yields. In this work this hypothesis is
      analyzed quantitatively, using numerical models of the population dynamics. These
      models suggest that reverse intersystem crossing alone cannot adequately explain
      the differences in biological response.

PMID- 11950088
TI  - Self-association of disulfonated deuteroporphyrin and its esters in aqueous
      solution and photosensitized production of singlet oxygen by the dimers.
AB  - Dimerization of free acid and ester forms of disulfonated deuteroporphyrin is
      investigated in aqueous solution by absorbance and fluorescence spectroscopies.
      The dimerization equilibrium constant increases with the extent of
      esterification. In phosphate buffer saline (pH 7.4, 20 degrees C), it ranges from
      1.4 x 10(6) M(-1) to 7.8 x 10(7) M(-1) for the free acid and the diethyl ester
      forms, respectively. The dimer formation is favored by an increase of ionic
      strength, as predicted by the Debye-Huckel law. The dimers display a marked shift
      to the blue of their Soret band. In agreement with the exciton model, a cofacial
      stacking of the molecules with some offset is postulated. The sulfonate groups on
      each molecule are likely to stand on opposite directions to reduce repulsion.
      Both the analysis of porphyrin self-association and careful examination of the
      fluorescence excitation spectra show that the dimers of disulfonated
      deuteroporphyrins do not fluoresce at all. The quantum yield of formation of
      singlet oxygen by the disulfonated deuteroporphyrins in deuterated methanol is
      0.71, a value typical of monomers. In deuterated water, the yield is 0.44 for all
      the compounds studied though they are dimerized. The fact that nonfluorescent
      dimers of porphyrins can be efficient photosensitizers is emphasized.

PMID- 11950089
TI  - Spectroscopic properties of fluoroquinolone antibiotics in water-methanol and
      water-acetonitrile mixed solvents.
AB  - The fluorescence properties of ofloxacin (OFL), norfloxacin (NOR) and flumequine
      (FLU) were studied in H2O-CH3OH and H2O-CH3CN mixed solvents because these
      solvents were thought to behave as a biological mimetic system. The emission
      spectra of OFL and NOR were very sensitive to the composition of the solvents. In
      the Lippert-Mataga analysis of the steady-state fluorescence data of OFL and NOR,
      clear reverse solvatochromism was exhibited in both mixed solvents. This
      observation can be explained by the twisted excited-state intramolecular charge
      transfer, which is accelerated by water. Theoretical treatments further support
      these results. The radiative and nonradiative rate constants were analyzed as a
      function of solvent dipolarity-polarizability (pi*) and hydrogen-bond donor
      acidity (alpha). These results were well consistent with the suggested mechanism
      of the excited-state chemical process of OFL and NOR, which depended upon the
      solvent-solute interactions such as bulk dielectric effects and specific hydrogen
      bonding interactions. However, the influence of dielectric effects was more
      significant. The solvent structures of H2O-CH3CN and the preferential solvation
      by water were also examined. The emission spectra of FLU do not exhibit any
      characteristic responses to the properties of the environment.

PMID- 11950090
TI  - Synthesis, spectra and photophysics of some free base tetrafluoroalkyl and
      tetrafluoroaryl porphyrins with potential applications in imaging.
AB  - The synthesis, characterization and photophysical properties of two
      perfluoroalkyl (5,10,15,20-tetrakis-[trifluoromethyl]- and [heptafluoropropyl]
      porphyrin) and two perfluoroaryl (5,10,15,20-tetrakis-[2,6-difluorophenyl]- and
      [pentafluorophenyl]-porphyrin) are described, with reference to their potential
      in both photodynamic therapy (PDT) and in vivo imaging by fluorescence and 19F
      nuclear magnetic resonance spectroscopy. Absorption and fluorescence spectra,
      fluorescence lifetimes and triplet-singlet difference spectra are reported.
      Triplet yields have been obtained by flash photolysis and pulse radiolysis,
      whereas yields of sensitized singlet oxygen formation have been determined by
      time-resolved phosphorimetry. All four compounds show high yields of triplet
      formation and singlet oxygen sensitization. The spectral properties, stability
      and attractive solubility characteristics of the perfluoroalkyl derivatives make
      them particularly suitable candidates for future study for applications in PDT.

PMID- 11950091
TI  - Development and application of a novel immunoassay for measuring oxidative DNA
      damage in the environment.
AB  - We developed a facile, cost-effective competitive binding assay for the analysis
      of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in DNA, using a polyclonal
      rabbit antiserum raised against an 8-oxodGuo hapten coupled to bovine serum
      albumin and radiolabeled synthetic ligand containing multiple 8-oxodGuo residues.
      This radioimmunoassay (RIA) displays a high affinity for 8-oxodGuo in DNA, with a
      detection limit of approximately 1 adduct in 10(5) bases of DNA. 8-oxodGuo
      standards for RIA were quantified by high-performance liquid chromatography and
      electrochemical detection in DNA diluted in methylene blue and exposed to visible
      light. As an initial application we quantified 8-oxodGuo in dosimeters deployed
      at increasing depths in the Southern Ocean during the austral spring of the 1998
      field season or at the surface at Palmer Station, Antarctica, throughout the 1999
      field season. Cyclobutane pyrimidine dimers (CPD) were quantified using an
      established RIA. We found that the frequency of both photoproducts decreased with
      depth. However, CPD induction was attenuated at a faster rate than 8-oxodGuo,
      correlating with the differential attenuation of solar ultraviolet wavelengths in
      the water column. CPD induction was closely related with ultraviolet-B radiation
      (UVB) attenuation, whereas the lower attenuation of 8-oxodGuo suggests that
      oxidative damage is more closely related to ultraviolet-A radiation (UVA)
      irradiance. The ratio of 8-oxodGuo: CPD was also found to covary with changes in
      stratospheric ozone concentrations at Palmer Station. These data demonstrate the
      usefulness of these assays for environmental photobiology and the potential for
      their use in studying the relative impacts of UVB versus UVA, including ozone
      depletion events.

PMID- 11950092
TI  - Seasonal fluctuation of DNA photodamage in marine plankton assemblages at Palmer
      Station, Antarctica.
AB  - Ultraviolet radiation-induced DNA damage frequencies were measured in DNA
      dosimeters and natural plankton communities during the austral spring at Palmer
      Station, Antarctica, during the 1999-2000 field season. We found that the fluence
      of solar ultraviolet-B radiation (UV-B) at the earth's surface correlated with
      stratospheric ozone concentrations, with significant ozone depletion observed
      because of "ozone hole" conditions. To verify the interdependence of ozone
      depletion and DNA damage in natural microbial communities, seawater was collected
      daily or weekly from Arthur Harbor at Palmer Station, Antarctica, throughout
      "ozone season," exposed to ambient sunlight between 0600 and 1800 h and
      fractionated using membrane filtration to separate phytoplankton and
      bacterioplankton populations. DNA from these fractions was isolated and DNA
      damage measured using radioimmunoassay. Under low-ozone conditions cyclobutane
      dimer concentrations in bacterioplankton and phytoplankton communities were
      maximal. DNA damage measured in dosimeters correlated closely with ozone
      concentrations and UV-B fluence. Our studies offer further support to the theory
      that stratospheric deozonation is detrimental to marine planktonic organisms in
      the Southern Ocean.

PMID- 11950093
TI  - Assessing carotenoid content in plant leaves with reflectance spectroscopy.
AB  - Spectral reflectance of maple, chestnut and beech leaves in a wide range of
      pigment content and composition was investigated to devise a nondestructive
      technique for total carotenoid (Car) content estimation in higher plant leaves.
      Reciprocal reflectance in the range 510 to 550 nm was found to be closely related
      to the total pigment content in leaves. The sensitivity of reciprocal reflectance
      to Car content was maximal in a spectral range around 510 nm; however,
      chlorophylls (Chl) also affect reflectance in this spectral range. To remove the
      Chl effect on the reciprocal reflectance at 510 nm, a reciprocal reflectance at
      either 550 or 700 nm was used, which was linearly proportional to the Chl
      content. Indices for nondestructive estimation of Car content in leaves were
      devised and validated. Reflectances in three spectral bands, 510+/-5 nm, either
      550+/-15 nm or 700+/-7.5 nm and the near infrared range above 750 nm are
      sufficient to estimate total Car content in plant leaves nondestructively with a
      root mean square error of less than 1.75 nmol/cm2.

PMID- 11950095
TI  - Relationship between mTHPC fluorescence photobleaching and cell viability during
      in vitro photodynamic treatment of DP16 cells.
AB  - An implicit dosimetric model has been proposed in which biological damage caused
      by photodynamic therapy (PDT) is monitored through the decrease in sensitizer
      fluorescence during treatment. To investigate this, in vitro experiments were
      performed in which DP16 cells were incubated in meta-tetra(hydroxyphenyl)chlorin
      (mTHPC) and then irradiated with 514 nm light. Photosensitizer concentration,
      fluence rate and oxygenation were independently controlled and monitored during
      the treatment. Fluorescence of mTHPC was continuously monitored via a charge
      coupled device-coupled spectrometer during treatment and, at selected fluence
      levels, cell viability was determined using a trypan blue exclusion assay. The
      relationship of cell viability to normalized fluorescence was obtained for the
      different treatment conditions. The relationship was independent of cell medium
      oxygenation, treatment fluence rate and sensitizer incubation concentration
      except at a high mTHPC concentration (4 microg/mL). This relationship suggests
      that fluorescence bleaching may be used to predict mTHPC PDT damage in vitro.

PMID- 11950094
TI  - In vivo mTHPC photobleaching in normal rat skin exhibits unique irradiance
      dependent features.
AB  - We report measurements performed on the normal skin of rats in vivo, which
      provide information on the photobleaching kinetics and mechanisms of the
      photosensitizer meso-tetrahydroxyphenyl chlorin (mTHPC). Loss of mTHPC
      fluorescence was monitored using in vivo fluorescence spectroscopy during
      photodynamic therapy (PDT) performed using 650 nm laser irradiation. The
      bleaching was evaluated for irradiances of 5, 20 and 50 mW cm(-2). Two distinct
      phases of mTHPC photobleaching were observed. In the first phase there was no
      obvious irradiance dependence in the loss of fluorescence vs fluence. The second
      phase was initiated by an irradiance-dependent discontinuity in the slope of the
      bleaching curve, after which the photobleaching rates showed an irradiance
      dependence consistent with an oxygen-dependent reaction process. To investigate
      the unusual shape of the in vivo bleaching curves, we measured the PDT-induced
      changes in O2 concentrations in mTHPC-sensitized spheroids irradiated with 2, 5
      and 20 mW cm(-2) of 650 nm light. The oxygen concentration data indicated no
      unusual features within the range of fluences where the discontinuities in
      fluorescence were observed during in vivo spectroscopy. The fluorescence from the
      in vivo bleaching experiments thus reports a phenomenon that is not reported by
      measurements of the photochemical oxygen consumption in the spheroids.

PMID- 11950096
TI  - Treatment of murine cutaneous melanoma with near infrared light.
AB  - Treatment of cutaneous melanoma (M-3 and B16-F10 implanted in mice) with rapidly
      scanned, tightly-focused near infrared light elicits selective destruction of
      tumor tissue. A single laser treatment yielded complete eradication in >90% of
      B16-F10 tumors with thicknesses of approximately 3 mm; amelanotic M-3 tumors
      proved less responsive (ca 25% clearance rate). In addition to local tumor
      destruction, laser treatment of B16-F10 tumors in immunocompetent mice stimulated
      enhanced cytokine levels (interleukin-2 and interleukin-10) within treated tumor
      tissues and rejection of tumor cells upon a subsequent challenge dose. Such an
      antitumor immune response may lead to improved outcomes at both the treatment
      site and at sites of distant metastasis.

PMID- 11950097
TI  - UVA irradiation-induced activation of activator protein-1 is correlated with
      induced expression of AP-1 family members in the human keratinocyte cell line
      HaCaT.
AB  - To determine whether the transcription factor activator protein-1 (AP-1) could be
      modulated by ultraviolet A (UVA) exposure, we examined AP-1 DNA-binding activity
      and transactivation after exposure to UVA in the human immortalized keratinocyte
      cell line HaCaT. Maximal AP-1 transactivation was observed with 250 kJ/m2 UVA
      between 3 and 4 h after irradiation. DNA binding of AP-1 to the target 12-O
      tetradecanoylphorbol-13-acetate response element sequence was maximally induced 1
      3 h after irradiation. Both de novo transcription and translation contributed to
      the UVA-induced AP-1 DNA binding. c-Fos was implicated as a primary component of
      the AP-1 DNA-binding complex. Other components of the complex included Fra-2, c
      Jun, JunB and JunD. UVA irradiation induced protein expression of c-Fos, c-Jun,
      Fra-1 and Fra-2. Phosphorylated forms of these induced proteins were determined
      at specific time points. A strong correlation existed between UVA-induced AP-1
      activity and accumulation of c-Fos, c-Jun and Fra-1 proteins. UVA irradiation
      also induced c-fos and c-jun mRNA expression and transcriptional activation of
      the c-fos gene promoter. These results demonstrate that UVA irradiation activates
      AP-1 and that c-fos induction may play a critical role in the response of these
      human keratinocytes to UVA irradiation.

PMID- 11950098
TI  - Cloning and characterization of an active fragment of luciferase from a
      luminescent marine alga, Pyrocystis lunula.
AB  - Two marine dinoflagellates, Lingulodinium polyedrum and Pyrocystis lunula, emit
      light in a reaction involving the enzymatic oxidation of its tetrapyrrole
      luciferin by molecular oxygen. The characteristic properties of P. lunula
      luciferase have not been clarified, whereas L. polyedrum luciferase, which has
      three active domains, has been characterized. A cloned partial cDNA of the P.
      lunula luciferase encodes an active fragment corresponding to part of domain 2
      and all of domain 3 of L. polyedrum luciferase. The homology of the amino acid
      sequence between the two luciferases in domain 3 is about 84.3%. A recombinant
      His-tagged luciferase fragment containing domain 3 (Mr = 46 kDa) catalyzed the
      light-emitting oxidation of luciferin (lambdamax = 474 nm). This protein was
      purified by a single affinity-chromatography procedure. The pH-activity profile
      and the bioluminescence spectrum of the recombinant enzyme having a third domain
      are almost identical to those of an extract from P. lunula cultured in vitro. The
      recombinant enzyme is active at pH 8.0, although the recombinant enzyme derived
      from the second domain of L. polyedrum luciferase is inactive at pH 8.0.
      Substitution of Glu-201 by histidine in the third domain of P. lunula luciferase
      showed a decrease of activity above pH 7.0, suggesting that histidine residues
      could be responsible for pH-sensitivity in dinoflagellate luciferase.

PMID- 11950099
TI  - Mass spectrometric analysis of porcine rhodopsin.
AB  - Rhodopsin is the dim light photosensitive pigment of animals. In this work, we
      undertook to study the structure of rhodopsin from swine and compare it with
      bovine and rat rhodopsin. Porcine rhodopsin was analyzed using methodology
      developed previously for mass spectrometric analysis of integral membrane
      proteins. Combining efficient protein cleavage and high performance liquid
      chromatography separation with the sensitivity of mass spectrometry (MS), this
      technique allows the observation of the full protein map and the
      posttranslational modifications of the protein in a single experiment. The
      rhodopsin protein from a single porcine eye was sequenced completely, with the
      exception of two single-amino acid fragments and one two-amino acid fragment, and
      the gene sequence reported previously was confirmed. The posttranslational
      modifications, similar to the ones reported previously for bovine and rat
      rhodopsin, were also identified. Although porcine rhodopsin has a high degree of
      homology to bovine and rat rhodopsins and most of their posttranslational
      modifications are identical, the glycosylation and phosphorylation patterns
      observed were different. These results show that rhodopsin from a single porcine
      eye can be characterized completely by MS. This technology opens the possibility
      of rhodopsin structural and functional studies aided by powerful mass
      spectrometric analysis, using the fellow eye as an internal control.

PMID- 11950100
TI  - Spectral shift of ultraweak photon emission from sweet potato during a defense
      response.
AB  - Consecutive spectral analyses of ultraweak photon emission from sweet potato
      showing a defense response were conducted to observe the process of physiological
      transition. The spectrum showed a drastic transition from 2 to 10 h after
      inoculation with Fusarium oxysporum, during which the emission intensity
      increased slowly. The spectrum was stable from 10 to 36 h after inoculation,
      whereas the emission intensity peaked approximately 20 h after inoculation. A
      change in the physiological state connected with the synthesis of defense-related
      substances is suggested as contributing to this phenomenon. The spectral
      transition was also detected in sweet potato treated with growth hormone or
      exposed to alternating temperature, although with an extremely weak emission
      intensity. This spectral analysis of ultraweak photon emission can be used as a
      new means for identifying the physiological state.

PMID- 11950101
TI  - Coping with body image changes following a disfiguring burn injury.
AB  - The influence of emotion-focused coping on distress following disfiguring injury
      was examined. Two types of emotion-focused coping (i.e., venting emotions vs.
      mental disengagement) were assessed in 78 patients with burn injury at baseline
      during acute hospitalization. Body image dissatisfaction (BID) was assessed 1
      week and 2 months following discharge. Use at baseline of both venting emotions
      and mental disengagement, compared with use of only one or neither of these
      coping methods, was associated at the 2-month postdischarge follow-up with
      significantly higher BID related to nonfacial aspects of appearance and with a
      greater negative social impact of disfigurement. D. M. Wegner's (1994)
      theoretical model of mental control and a proposed motivational analysis are used
      to interpret these findings.

PMID- 11950102
TI  - Stress and smoking in adolescence: a test of directional hypotheses.
AB  - The authors conducted a comparative test of the hypotheses that (a) stress is an
      etiological factor for smoking and (b) cigarette smoking causes increases in
      stress (A. C. Parrott, 1999). Participants were a sample of 1,364 adolescents,
      initially surveyed at mean age 12.4 years and followed at 3 yearly intervals.
      Measures of negative affect, negative life events, and cigarette smoking were
      obtained at all 4 assessments. Latent growth modeling showed negative affect was
      related to increase in smoking over time; there was no path from initial smoking
      to change in negative affect. Comparable results were found for negative life
      events, with no evidence for reverse causation. Results are discussed with
      respect to theoretical models of nicotine effects and implications for
      prevention.

PMID- 11950103
TI  - Risk factors for binge eating onset in adolescent girls: a 2-year prospective
      investigation.
AB  - Because little is known about the predictors of binge eating (a risk factor for
      obesity), a set of putative risk factors for binge eating was investigated in a
      longitudinal study of adolescent girls. Results verified that binge eating
      predicted obesity onset. Elevated dieting, pressure to be thin, modeling of
      eating disturbances, appearance overvaluation, body dissatisfaction, depressive
      symptoms, emotional eating, body mass, and low self-esteem and social support
      predicted binge eating onset with 92% accuracy. Classification tree analysis
      revealed an interaction between appearance overvaluation, body mass, dieting, and
      depressive symptoms, suggesting qualitatively different pathways to binge eating
      and identifying subgroups at extreme risk for this outcome. Results support the
      assertion that these psychosocial and biological factors increase risk for binge
      eating.

PMID- 11950105
TI  - Perceptual consequences of an illness-concern induction and its relation to
      hypochondriacal tendencies.
AB  - This article examines the perceptual consequences of activating illness concern
      as a function of hypochondriacal tendencies. In 2 independent samples,
      hypochondriacal tendencies were associated with slower reaction times on a
      modified emotional Stroop task when the stimulus words were illness related, but
      only when illness concern was activated. Moreover, these findings emerged when
      hypochondriacal tendencies were defined as a sensitivity to bodily sensations.
      When defined as illness preoccupation and fear, hypochondriacal tendencies were
      associated with a generalized pattern of perseveration to all stimuli when health
      concern was activated. Finally, the results persisted even after statistically
      controlling for state anxiety. Findings are discussed within the context of an
      activation hypothesis and highlight the importance of the operational definition
      and assessment of hypochondriacal tendencies when examining perceptual biases.

PMID- 11950104
TI  - The DRD4 VNTR polymorphism moderates craving after alcohol consumption.
AB  - Recent research has suggested that alterations in mesolimbic dopamine
      neurotransmission are central to the development and expression of craving for
      alcohol. Because the D4 dopamine receptor gene, variable numbers of tandem
      repeats (DRD4 VNTR) polymorphism putatively expresses functional differences in
      dopamine receptors, the present study tested whether this polymorphism influences
      the effects of a priming dose of alcohol on craving. Participants consumed 3
      alcoholic drinks or 3 control drinks and completed measures of craving after each
      drink. Participants who were homozygous or heterozygous for the 7 (or longer)
      repeat allele were classified as DRD4 L, whereas the other participants were
      classified as DRD4 S. Results suggested that DRD4 L participants demonstrated
      significantly higher craving after consumption of alcohol as compared with the
      control beverage.

PMID- 11950106
TI  - An examination of the physical health, health care use, and psychological well
      being of spouses of people with fibromyalgia syndrome.
AB  - The present study compared the physical and mental health and the health care use
      of spouses of patients with fibromyalgia syndrome (FS group; n = 135) with that
      of spouses of healthy individuals (n = 153). FS group participants reported lower
      health and affective states and scored higher on depression, loneliness, and
      subjective stress than comparison group participants (p < .017). Husbands in the
      FS group who reported more illness impact and whose wives reported worse sleep
      quality and less self-efficacy had more psychological difficulties. No
      differences were found in health care costs between groups. These findings
      suggest that chronic illness in a partner may negatively affect an individual's
      physical and mental health.

PMID- 11950107
TI  - Negative reactions to received spousal care: predictors and consequences of
      miscarried support.
AB  - This study focused on the negative reactions of older women with osteoarthritis
      to the receipt of instrumental support (i.e., physical assistance) from their
      husbands and the effects of such negative reactions on the women's psychological
      well-being and self-care. Applying a person-environment fit model, the authors
      predicted that women's negative reactions to spousal support would be determined
      by the fit between this support and the personal centrality (importance) of being
      functionally independent. Consistent with this prediction, women who received
      high levels of support from the husband and for whom being functionally
      independent was not highly central reacted less negatively to this support. More
      negative reactions to spousal support were related to greater concurrent
      depressive symptomatology and fewer self-care behaviors. In addition, negative
      reactions were predictive of the women's increased depressive symptomatology and
      decreased life satisfaction. Findings illustrate a useful theoretical approach to
      the examination of support from family caregivers.

PMID- 11950108
TI  - Information-motivation-behavioral skills model-based HIV risk behavior change
      intervention for inner-city high school youth.
AB  - This study assessed the effects of 3 theoretically grounded, school-based HIV
      prevention interventions on inner-city minority high school students' levels of
      HIV prevention information, motivation, behavioral skills, and behavior. It
      involved a quasi-experimental controlled trial comparing classroom-based, peer
      based, and combined classroom- and peer-based HIV prevention interventions with a
      standard-of-care control condition in 4 urban high schools (N = 1,532, primarily
      9th-grade students). At 12 months postintervention, the classroom-based
      intervention resulted in sustained changes in HIV prevention behavior. This
      article discusses why both of the interventions involving peers were less
      effective than the classroom-based intervention at the 12-month follow-up and,
      more generally, suggests a set of possible limiting conditions for the efficacy
      of peer-based interventions.

PMID- 11950109
TI  - Breast-feeding is associated with reduced perceived stress and negative mood in
      mothers.
AB  - Two studies examined the effects of breast-feeding on maternal stress and mood.
      In Experiment 1, perceived stress in the past month was compared between 28
      breast-feeding and 27 bottle-feeding mothers. Breast-feeding mothers reported
      less perceived stress, after controlling for demographic confounds. In Experiment
      2, mood ratings were assessed in the same 24 mothers both before and then after 1
      breast-feeding and 1 bottle-feeding session. Breast-feeding was associated with a
      decrease in negative mood, and bottle-feeding was associated with a decrease in
      positive mood from pre- to postfeeding. Results indicated that breast-feeding
      buffers negative mood. These effects appeared to be attributable to the effects
      of breast-feeding itself and not solely to individual-differences factors.

PMID- 11950110
TI  - The theory of planned behavior and healthy eating.
AB  - Application of the theory of planned behavior (TPB) to healthy eating in 144
      health promotion clinic attendees is reported. Respondents completed self-report
      TPB measures after the clinic (Time 1) and 6 months later (Time 2) with a measure
      of perceived past behavior. Intention stability was assessed on Time 1-2
      differences. Six years later (Time 3), respondents completed measures of healthy
      eating intentions and behavior. Intentions were predicted by attitudes, perceived
      behavioral control, and perceived past behavior (cross-sectionally). Healthy
      eating behavior (Time 3) was predicted from intentions (Time 2). As intention
      stability increased, intentions and perceived past behavior became stronger and
      weaker predictors of behavior, respectively. Implications for understanding
      health cognitions in long-term performance of health behavior are discussed.

PMID- 11950111
TI  - Hostility explains some of the discrepancy between daytime ambulatory and clinic
      blood pressures.
AB  - The authors examined whether hostility explained the discrepancy commonly
      observed between clinic and daytime ambulatory blood pressures. Daytime
      ambulatory blood pressure (DABP) was assessed every 45 min over 6 days in healthy
      adults (N = 120). After controlling for demographic variables, time-varying
      covariates such as position and activity level, and clinic blood pressure (CBP),
      the Cook-Medley Hostility Scale was significantly associated with daytime
      ambulatory diastolic blood pressure. No support was obtained for mediation by
      psychological factors. Discrepancies between DABP and CBP may be due, in part, to
      differences in the degree to which these 2 types of measures are associated with
      individual differences in hostility. These results suggest that the addition of
      hostility to CBP may improve its predictive power.

PMID- 11950112
TI  - Reducing infant immunization distress through distraction.
AB  - Infant procedural distress is largely understudied, and there is a dearth of
      empirically supported interventions in the child health psychology literature.
      This study examined nurse-directed distraction for reducing infant immunization
      distress. Ninety infants and their parents were randomly assigned to a
      distraction condition (i.e., nurses used stimuli to divert infants' attention) or
      a typical care condition. Outcome measures were an observational scale, parent
      and nurse ratings, and infant heart rate. Results indicated that infants engaged
      in distraction and that distraction reduced their behavioral distress; however,
      ratings and heart rate were inconclusive. Analyses of procedural phases indicated
      that infants exhibited elevated distress immediately prior to and during an
      injection, but this distress was fleeting.

PMID- 11950114
TI  - Seasonal prevalence of anti-Japanese encephalitis virus antibody in pigs in
      different regions of Taiwan.
AB  - Although the endemic season of Japanese encephalitis lasts from May through
      October, sporadic cases occur in other months of the year. To appreciate the real
      situation of Japanese encephalitis virus (JEV) activity throughout the year, a
      survey was conducted using hemagglutination-inhibition test to detect the
      presence of anti-JEV antibodies in pigs' sera, which were collected from 4
      regions of Taiwan between January 2000 and January 2001. Results indicate that
      (1) JEV-infected pigs were found throughout the year; (2) the prevalence rates of
      JEV in the 4 regions in descending order were 70% in Miaoli, 59% in Hualien, 52%
      in Pingtung, and 49% in Nantou; (3) similar to that in 1990, the peak endemic
      months appeared 1 month after the date of 50% seroconversion (May 21, 2000); (4)
      infected pigs were present during the period from December through April as a
      reservoir for over-wintering of JEV; and (5) there was a suggestive evidence for
      the occurrence of sporadic cases of JEV during the December-April period. In
      conclusion, JEV propagates and is active indigenously in the winter as well as
      other seasons of the year.

PMID- 11950113
TI  - Antibiotics: action and resistance in gram-negative bacteria.
AB  - Therapeutic control of beta-lactamase-producing bacteria has been a major
      clinical problem in the past 40 years. Gram-negative bacteria are most often
      resistant to antibiotics as a result of the acquisition of resistant genes or
      gene mutation. Studies have shown that newly developed antibiotics will shortly
      fail to be active against the bacteria because of the emergence of resistance.
      Some resistant bacteria have been found to exist even before the antibiotic was
      developed. Selective pressure by the antibiotic is, therefore, one of the major
      factors to explain the increase of resistance. Recently, numerous resistant
      mechanisms that differ in their substrate profiles have been described at
      increasing frequencies. The inappropriate use of new antibiotics with extended
      spectrum further complicated the problem. Because resistance is a largely
      unavoidable consequence of widespread use of antibiotics, it is crucial that the
      use of drugs is selective by exercising prudent judgment and not excessive. The
      actual prevalence of resistance should be continuously monitored each year.
      Caution should be paid to the direct extrapolation of study results from other
      geographic areas, because the local prevalence of resistance is unlikely to be
      identical to those reported elsewhere. The impact of resistance to an antibiotic
      and its specific mechanisms, including transmissibility, should also be carefully
      studied. Such information may help in designing strategies for maximizing the
      therapeutic usefulness of drugs and minimizing the emergence of resistance.

PMID- 11950115
TI  - Streptococcus pneumoniae bacteremia in southern Taiwan.
AB  - Streptococcus pneumoniae bacteremia was diagnosed in 33 patients between June
      1999 and November 2000 at the Chang Gung Memorial Hospital-Kaohsiung in southern
      Taiwan. Antimicrobial susceptibility and serotyping of the clinical isolates were
      performed. Pneumonia was diagnosed in 19 patients, primary bacteremia in 13, and
      meningitis in one. The most common serotypes were types 14, 3, and 23F. Fourteen
      (42.4%) isolates of S. pneumoniae were non-susceptible to penicillin. High
      antimicrobial resistance rates were found to erythromycin (81.9%), tetracycline
      (69.7%), clindamycin (69.7%), trimethoprim-sulfamethoxazole (33.1%), and
      chloramphenicol (12.1%). The mortality was 42.4% and liver cirrhosis was an
      independent risk factor for mortality (odds ratio = 9.998; 95% confidence
      interval, 1.011-98.85; p=0.049). All isolated strains were covered by 23-valent
      the pneumococcal vaccine. Given the increasing prevalence of penicillin non
      susceptible S. pneumoniae infection in the community, ongoing periodic monitoring
      of the evolutionary clinical situation is needed. Results of this study suggest
      that patients with liver cirrhosis should be inoculated with pneumococcal
      vaccine.

PMID- 11950116
TI  - Clinical outcome of invasive pneumococcal infection in children: a 10-year
      retrospective analysis.
AB  - A retrospective study was conducted on 72 children admitted to a medical center
      in Taiwan due to invasive pneumococcal infections diagnosed between January 1990
      and April 2000. Of these patients, 28 had meningitis and 44 had other invasive
      diseases. Forty-one (56.9%) strains of Streptococcus pneumoniae showed reduced
      susceptibility to penicillin by the oxacillin disc diffusion method. The total
      mortality was 20.8%, 32.1% for meningitis, and 13.6% for other invasive diseases.
      Ten (52.6%) of the patients survived from meningitis had long-term sequelae.
      Statistical analysis showed that initial presentation of coma, shock, respiratory
      distress requiring mechanical ventilation, and leukopenia (leukocyte <4,000 /mm3)
      were associated with mortality of invasive pneumococcal infections. Low
      cerebrospinal fluid leukocyte count (<50 /mm3) and high cerebrospinal fluid
      protein level (> or = 660 mg/dL) were also associated with mortality of
      meningitis. The presence of underlying diseases and high alanine aminotransferase
      level (> or = 100 U/L) were associated with fatal non-meningitic invasive
      diseases. Patients with shock and high alanine aminotransferase level but without
      high C-reactive protein level (> or = 20 mg/dL) were associated with rapidly
      fatal outcome. The outcome of invasive pneumococcal diseases was not associated
      with penicillin susceptibility.

PMID- 11950118
TI  - Comparison of clinical characteristics of adenovirus and non-adenovirus pneumonia
      in children.
AB  - Forty-eight cases of adenovirus pneumonia in children were treated in the
      Department of Pediatrics of Taipei Veterans General Hospital from January 1998
      through December 2000. The clinical characteristics of these patients were
      compared with those of a control group of 70 patients with non-adenovirus
      pneumonia mostly caused by Mycoplasma pneumoniae and other viruses during the
      same period. No difference was found between the adenovirus and non-adenovirus
      groups in age, sex, duration of fever, and hospitalization days. Chest retraction
      and extrapulmonary manifestations were significantly more common in the
      adenovirus group, especially conjunctivitis, gastroenteritis, lymphadenopathy,
      bleeding diathesis, and exanthema. C-reactive protein levels were significantly
      higher in the study group than in the control group. In the adenovirus group, 2
      patients died and 5 had permanent lung damage after adenovirus infections. No
      mortality or long-term sequelae were found in the non-adenovirus group.
      Adenovirus may cause diseases manifesting predominantly as fever and lower
      respiratory tract infection that may require hospitalization. Extrapulmonary
      manifestations were observed in more than half of children with adenovirus
      infections. Adenoviral pneumonia can be fatal and permanent lung damage may be
      noted during the follow-up period.

PMID- 11950117
TI  - Clinical manifestations of strongyloidiasis in southern Taiwan.
AB  - The diagnosis and management of strongyloidiasis present a continuous challenge
      in developing countries including Taiwan. In this study, the clinical
      characteristics and microbiological findings of 27 patients with Strongyloides
      stercoralis infection were retrospectively analyzed. Intestinal infection was
      identified in 17 patients and hyperinfection syndrome or disseminated disease in
      10 (including 2 autopsy cases). The most frequent clinical findings were diarrhea
      (74%), fever (70%), abdominal pain (59%), cough (37%), dyspnea (33%), and
      constipation (26%). The common initial laboratory abnormalities were leukocytosis
      (81%), anemia (67%), liver function impairment (52%), and eosinophilia (44%).
      Most of the 27 patients had comorbid conditions, including malnutrition in 20
      (74%), corticosteroid dependence in 15 (55%), chronic obstructive pulmonary
      disease in 9 (33%), chronic liver disease or cirrhosis in 8 (30%), and peptic
      ulcer disease in 7 (26%). There was no difference in the time interval from
      symptom onset to diagnosis between the intestinal infection group and the
      hyperinfection/disseminated group (22 +/- 15 vs 17 +/- 9 days). Larvae of S.
      stercoralis were identified in the stool of 24 patients, in the sputum smear of
      5, in the gastric biopsy of one, and on histology of autopsy specimens in 2.
      Twenty-six patients received antiparasitic drug therapy of variable duration
      (mebendazole in 24, albendazole in 2, combined therapy in one). The overall cure
      rate was 52% (14/27). Relapse occurred in 4 patients. The overall mortality was
      26% (7/27). There was a high mortality (up to 50%) in the
      hyperinfection/disseminated disease group. In conclusion, diagnosis of
      strongyloidiasis is often delayed and overlooked because of nonspecific symptoms.
      Physicians in endemic regions should include strongyloidiasis in the differential
      diagnosis when patients present with gastrointestinal and/or pulmonary symptoms
      with peripheral eosinophilia.

PMID- 11950119
TI  - Mycobacterium marinum infection in Taiwan.
AB  - Mycobacterium marinum often causes skin infections, tenosynovitis, arthritis, and
      osteomyelitis, and occasionally results in severe disseminated infections in
      immunocompromised patients. In this study, the clinical features of 14 cases of
      M. marinum infection were retrospectively analyzed. One patient had septic
      arthritis, the other 13 had skin infections and/or tenosynovitis. It usually took
      2 months or longer for a definite diagnosis to be made in these patients. Three
      of the 14 patients were cured using clarithromycin alone or in combination with
      rifampin plus ethambutol. Most patients did not respond to conventional
      antituberculosis agents. Pulsed-field gel electrophoresis and infrequent
      restriction-site polymerase chain reaction are efficient tools for the molecular
      typing of M. marinum. Both methods yielded a concordant result, and 4 of 12
      isolates were genetically closely related to each other based on their banding
      patterns. This study indicates that these isolates were derived from the same
      clone. Because M. marinum infection is curable, early diagnosis is important.
      Poor healing of wounds after exposure to aquatic animals appears to be the most
      important clinical clue indicating the need for culture and inclusion of M.
      marinum infection in the differential diagnosis.

PMID- 11950120
TI  - Characteristics of Plesiomonas shigelloides infection in Taiwan.
AB  - From January 1999 through December 2000, a total of 111 cases of Plesiomonas
      shigelloides infections were diagnosed in a medical center of northern Taiwan.
      The patients ranged in age from 22 days to 72 years. One third (39/111, 35%) of
      the positive cultures were found in young children (<2 years old). There was no
      significant difference in the incidence between males (56/111, 50%) and females
      (55/111, 50%). The peak seasons for the disease were summer (45/111, 41%) and
      autumn (42/111, 38%). The major clinical presentations in children were diarrhea
      (66/69, 96%) and fever (38/69, 55%), whereas diarrhea (41/42, 98%) and abdominal
      pain (30/42, 71%) were the most common presentations in adults. Most adults with
      P. shigelloides infection visited the emergency room (38/42, 90%) and received
      empirical antimicrobials (37/42, 88%), whereas children were more likely to be
      treated as outpatients (53/69, 77%) and inpatients (27/69, 39%). One third
      (23/69, 33%) of pediatric patients had mixed enteric infection, and 74% (17/23)
      of them were younger than 2 years. Salmonella species (17/24, 71%), especially
      group B Salmonella (12/17, 71%), were the most common mixed enteric pathogen. The
      disease is usually mild and self-limited. Symptomatic management is adequate and
      antimicrobial therapy is seldom required.

PMID- 11950121
TI  - Characteristics of community-acquired methicillin-resistant Staphylococcus aureus
      in infants and children without known risk factors.
AB  - This retrospective study sought to determine the characteristics of community
      acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in
      patients younger than 18 years without known risk factors who were treated at a
      teaching hospital in central Taiwan. Epidemiological and clinical data were
      collected from medical charts. Possible risk factors included hospitalization
      within the past 6 months, transfer from other hospitals or nursing homes, and
      having underlying illness. A total of 173 isolates of community-acquired S.
      aureus were analyzed. Seventeen (9.8%) of these 173 isolates were methicillin
      resistant S. aureus collected from patients without risk factors, 31 (17.9%) were
      methicillin-resistant S. aureus from patients with risk factors, and the other
      125 (72.3%) were methicillin-susceptible S. aureus. Most isolates of community
      acquired methicillin-resistant S. aureus collected from patients without risk
      factors (14/17, 82.4%) were obtained from the infected wounds of skin or soft
      tissues. Only 4 (23.5%) in 17 patients with isolates resistant to methicillin
      were prescribed antimicrobial therapy with glycopeptides. Nevertheless, all
      patients recovered without any long-term sequelae. These results highlight the
      fact that community-acquired methicillin-resistant S. aureus infections occur
      frequently in Taiwan among patients who have no established risk factors for this
      infection.

PMID- 11950122
TI  - Clinical features of atypical Kawasaki disease.
AB  - From 1989 through 1998, a total of 132 children admitted to the National Taiwan
      University Hospital were identified as having Kawasaki disease. Twenty (15%) of
      them did not meet the diagnostic criteria of Kawasaki disease, but were
      considered atypical Kawasaki based on the specific clinical signs and exclusion
      of other causes by serologic study and culture result. The patients' age ranged
      from 5 months to 11 years, with a mean of 22.2 months and a median of 15 months.
      The male to female ratio was 1.9:1. Twenty-five percent (5/20) of them had
      coronary arterial lesion. No difference was found in the age distribution, sex,
      and rate of coronary artery involvement between typical and atypical Kawasaki
      disease. All patients were treated with intravenous immunoglobulin and aspirin
      except for 2 patients. At follow-up, patients with coronary arterial lesions had
      a prognosis as good as those with typical Kawasaki disease. According to these
      observations, atypical Kawasaki disease may be part of Kawasaki disease occurring
      via the same pathogenesis, but has incomplete manifestation. Clinical
      practitioners should have a high index of suspicion to diagnose and initiate
      prompt treatment to reduce the comorbidity of coronary arterial disease in
      patients with atypical Kawasaki disease.

PMID- 11950123
TI  - Haemophilus influenzae type b meningitis with subdural effusion: a case report.
AB  - Haemophilus influenzae type b causes invasive infection in children under 2 years
      of age. The disease may be complicated with hearing impairment, lowered learning
      ability, and other neurologic sequelae. The incidence of invasive H. influenzae
      type b has declined dramatically after the introduction of routine administration
      of protein-conjugated H. influenzae type b vaccine in the United States and some
      other countries. Because of its low incidence in Taiwan, many clinicians are not
      familiar with the initial symptoms and management of H. influenzae type b. This
      case report describes a 7-month-old H. influenzae type b meningitis patient who
      had initial presentations of prolonged intermittent fever and vague neurologic
      signs. Left peripheral facial palsy with hearing loss in left ear and bilateral
      frontal subdural effusion developed during the first 5 days of cefotaxime
      therapy. Betamethasone was then given for 4 days to relieve the severe
      inflammation. Drug-induced fever was observed after 11 days of antibiotic use and
      subsided with prednisolone treatment. Left ear hearing impairment persisted
      during the follow-up period, but the children did not experience other
      significant development delay.

PMID- 11950124
TI  - Haemophilus parainfluenzae and Fusobacterium necrophorum liver abscess: a case
      report.
AB  - Liver abscess is a potentially life-threatening disease. The clinical features of
      pyogenic liver abscess are variable and probably correlate with a variety of
      pathogenic microorganisms and underlying diseases that may be involved. The most
      common pathogen of liver abscess in Taiwan is Klebsiella pneumoniae. Diabetes
      mellitus and hepatobiliary calculus are major diseases associated with liver
      abscess. Haemophilus parainfluenzae is a commensal of the upper respiratory
      tract, but is an uncommon isolate in liver abscess. We describe a 44-year-old man
      with liver abscess caused by mixed H. parainfluenzae and Fusobacterium
      necrophorum infection. He received percutaneous liver abscess drainage and
      intravenous antibiotic therapy for 3 weeks and fully recovered. No recurrence
      occurred during the follow-up period of 4 months.

PMID- 11950125
TI  - Detection of giardia cysts and cryptosporidium oocysts in central Taiwan rivers
      by immunofluorescence assay.
AB  - From November 1998 through 1999, water samples collected from the Faze, Kanwe,
      and Dajia rivers were analyzed using a combined immunofluorescence antibody
      method for detecting cysts of Giardia spp. and oocysts of Cryptosporidium spp.
      Water samples of the Kanwe River were collected downstream of a piggery; 5 to 469
      cysts and 11 to 1,102 oocysts per 100 L were found in the water samples. The
      sampling site of the Faze River was upstream of the same piggery, and there were
      110 cysts and 188 oocysts per 100 L of water samples. Water samples from the
      Dajia River were taken from an inlet of a water purification plant. There were 0
      to 14.4 cysts and 14.3 to 50.5 oocysts per 100 L of water samples. Results
      indicate that the presence of Giardia cysts and Cryptosporidium oocysts in the
      surface water is closely related to the discharge of piggery wastes. Cysts and
      oocysts were found less often in the source water of a water purification plant.

PMID- 11950127
TI  - Improved medication use in long-term care: building on the consultant
      pharmacist's drug regimen review.
AB  - Elderly and long-term care (LTC) patients often require complex medication
      regimens that increase their risk of adverse drug events or suboptimal
      pharmacotherapy. Currently, oversight of medication use in LTC facilities
      consists of a federally mandated monthly audit, the drug regimen review (DRR),
      performed by a consultant pharmacist, and yearly onsite government surveys.
      Although the DRR's purpose is to improve drug use and to avoid adverse drug
      events, the Centers for Medicare and Medicaid Services's (CMS) current DRR
      guidelines focus on a limited selection of medications and indications rather
      than on patient outcomes. An expanded model building on CMS's survey guidelines
      and the American Society of Consultant Pharmacists' Fleetwood Model is proposed
      to improve oversight of medication use. The proposed model includes using
      consultant pharmacists with demonstrated geriatric pharmacotherapy expertise,
      direct patient assessments by the pharmacist, increased interaction among
      healthcare professionals, evidence-based practices, and explicit patient outcome
      assessments. It is both feasible and timely: (1) the LTC prospective payment
      system aligns financial incentives between payers and providers; and (2) the
      Institute of Medicine has made quality improvement and error reduction a
      priority.

PMID- 11950128
TI  - Capitation payment, length of visit, and preventive services: evidence from a
      national sample of outpatient physicians.
AB  - OBJECTIVE: To test the hypothesis that capitation payment to physicians reduces
      the length of physician-patient encounters but increases use of preventive and
      health counseling services. STUDY DESIGN: Cross-sectional analysis of data from
      the National Ambulatory Medical Care Survey of outpatient physicians and their
      office staff (1997 and 1998). PATIENTS AND METHODS: A random national sample of
      46,320 ambulatory care visits was used. Weight-adjusted multivariate regression
      techniques were utilized to examine the effects of capitation on duration of
      physician visit and number of preventive and health counseling services. RESULTS:
      Physicians spent 5.6% less time (P < .01) with patients in capitated plans than
      with those in noncapitated plans. The effect of payment method on length of visit
      was 3.5 times stronger among physicians receiving only capitated payment,
      compared with physicians receiving only noncapitated payment. Patients in
      capitated plans were 17% more likely to receive health counseling services (P <
      .01) than patients in noncapitated plans. Patients under capitation were 3% more
      likely to receive preventive services compared to patients in non-health
      maintenance organizations, noncapitated plans (P < .05). CONCLUSIONS: Capitation
      is associated with a modest decrease in the amount of time physicians spend with
      their patients and with increased receipt of preventive and health counseling
      services, on average. These trends are driven by physicians who receive capitated
      payment predominantly. Physicians with a mix of patients from capitated and
      noncapitated plans spend approximately equal time with each type of patient,
      which reflects an ethic of impartiality in medical judgment.

PMID- 11950129
TI  - An analysis of patient compliance with nurse recommendations from an after-hours
      call center.
AB  - OBJECTIVES: To demographically and clinically describe the callers who use an
      after-hours call center (AHCC); to estimate the level of patient satisfaction
      with the AHCC; to determine caller compliance with the AHCC nurse's
      recommendation; and to examine the relationship between compliance and selected
      demographic and clinical characteristics, including caller satisfaction. STUDY
      DESIGN: A prospective, quasi-experimental telephone survey. PATIENTS AND METHODS:
      Randomly selected callers (n = 427) to an AHCC were surveyed by telephone to
      determine their satisfaction with the services provided and their compliance with
      the AHCC nurse's recommendation. RESULTS: Overall, 88.2% of the AHCC clients were
      compliant with the nurse's recommendations. Logistic regression analysis revealed
      that 2 patient variables had a statistically significant impact on compliance.
      Patients or their surrogates (eg, parents/guardians, caregivers) who were "very
      satisfied" were more than 4 times more likely to be compliant, and the surrogates
      of the patients under the age of 1 year were more than 20 times more likely to be
      compliant. The greatest level of patient dissatisfaction was with the time it
      took to make contact with the nurse. Decreasing this response time may improve
      satisfaction, which in turn may increase compliance and lead to more desirable
      health outcomes. CONCLUSIONS: The level of compliance was found to be favorable
      for all levels of acuity. However, the results indicate a further need for
      quality improvement activities.

PMID- 11950130
TI  - Disease management practices of health plans.
AB  - OBJECTIVE: To investigate how health plans manage chronic diseases. STUDY DESIGN:
      Health plan medical directors were surveyed regarding the disease management (DM)
      practices of their plans. METHODS: We took a stratified random sample of 65
      plans, all members of the American Association of Health Plans. Forty-five plans
      responded. Results were weighted to be representative of the industry (including
      nonmember plans). Medical directors were asked to consider that they had a DM
      program only if 2 things were true: (1) A majority of a plan's enrollees could
      not be ineligible for a DM program for non-clinical reasons (eg, geographic
      location); and (2) a DM program had to have at least 6 of the 8 components of a
      DM program as defined by the Disease Management Association of America. RESULTS:
      The 3 diseases most likely to be the focus of DM programs were diabetes, asthma,
      and congestive heart failure. For each of these diseases, at least one quarter of
      Americans were enrolled in plans offering a DM program. Medical directors
      perceived their DM programs to be highly effective in reducing mortality and
      morbidity and in improving the functional status of patients, and perceived them
      to be effective in lowering cost. The greatest challenge in implementing DM
      programs involves information technology. These results yield insights into the
      future of treatment of chronic disease in the United States. CONCLUSION: Health
      plans have made a significant investment in programs to improve care for chronic
      illness. The almost universality of DM programs highlight the need for scholarly
      evaluations of their effectiveness and cost effectiveness.

PMID- 11950132
TI  - Competitive bidding for interventional cardiology supplies: lessons learned
      during round 2.
AB  - OBJECTIVE: To assess the magnitude of savings and develop concepts for "best
      strategies" in reducing costs in the purchasing of high-technology, high-cost
      materials used in coronary interventions and electrophysiologic treatments. STUDY
      DESIGN: Observational experience in competitive bidding for defibrillators,
      pacemakers, coronary stents, and coronary balloon catheters at a large,
      midwestern, publicly owned, academic cardiovascular center. METHODS: Iterative
      negotiation following a broad request for proposal sent to a diverse group of
      vending organizations in high-technology areas of cardiology. Product costs and
      volume usage were assessed before and after the process to estimate annualized
      cost reduction achieved. RESULTS: Using a combination of identification of
      preferred vendors; consignment of supplies; and collaborative consensus among
      physicians, administration, materials management, purchasing, and vendors, an
      annualized savings of more than $1.3 million was achieved. CONCLUSIONS:
      Aggressive, collaborative, fair, and competitive bidding for high-cost products
      used for coronary interventions and electrophysiologic treatments leads to
      substantial cost savings and can promote provider-industry partnerships that
      further enhance product use, provision, and tracking.

PMID- 11950131
TI  - Performance of the provider recognition program's survey to assess patient
      satisfaction with the provision of diabetes care in primary care.
AB  - OBJECTIVE: To measure, for the first time, the performance of the American
      Diabetes Association-National Committee for Quality Assurance Provider
      Recognition Program (PRP) survey in assessing patient satisfaction with the
      provision of diabetes care. STUDY DESIGN: Postal survey. PATIENTS AND METHODS:
      The PRP survey satisfaction questions and the Diabetes Treatment Satisfaction
      Questionnaire were mailed to a random sample of 607 patients with diabetes
      attending 3 medical practices (63 primary care providers), with an additional
      mailing to nonresponders. RESULTS: On face validity, the PRP survey incompletely
      addressed satisfaction with the provision of diabetes care. The response rate was
      67%. The items in the PRP survey were correlated internally (Cronbach alpha
      coefficient = .89) and with the Overall Satisfaction scale (r = 0.40-0.56; P <
      .001 for all) of the Diabetes Treatment Satisfaction Questionnaire (concurrent
      validity). The instrument was skewed toward satisfaction. After recoding all less
      than-totally satisfied responses as expressing dissatisfaction, 25% of the
      surveys indicated dissatisfaction with diabetes care. CONCLUSIONS: The PRP
      patient satisfaction survey is an internally consistent and valid measure of
      patient satisfaction. However, it is incomplete and skewed toward satisfaction.
      Development of a patient dissatisfaction metric might play a more significant
      role in orienting quality improvement efforts and benchmarking.

PMID- 11950133
TI  - Phylogenetic comparison and artificial selection. Two approaches in evolutionary
      physiology.
AB  - Interspecific comparison has a long and productive history in physiology.
      Conceptual and statistical advances over the last 15 years have demonstrated
      several ways in which comparisons can be enhanced by consideration of
      phylogenetic information, i.e., empirical estimates of the ways in which
      organisms are related (evolutionary trees). Choice of species to be compared
      should be informed by phylogenetic information. For example, a comparison of
      three species that inhabit high altitude with three that live at low altitude
      would be suspect if each of the two groups were composed of closely-related
      species (e.g., within single genera). To avoid such "phylogenetic
      pseudoreplication," one might instead study species from three different genera,
      each containing one high-altitude and one low-altitude inhabitant. Unfortunately,
      many studies have not been so carefully designed, sometimes because organisms
      were not accessible or because the studies incorporated data from the literature.
      Fortunately, several new statistical methods correct for problems caused by
      phylogenetic relatedness and descent with modification, the most common being
      phylogenetically independent contrasts. Another tool that can be used in
      comparative physiology is selective breeding, which has been practiced for
      millennia and applied in scientific contexts for over a century. In the last 20
      years, ecological and evolutionary physiologists have begun using selection
      experiments to study processes of genetic adaptation in physiological and
      behavioral traits. For example, house mice have been maintained in the cold for
      multiple generations to see what adaptations may occur naturally in response to
      reduced ambient temperature ("laboratory natural selection"). Our own laboratory
      has used selective breeding to create four replicate lines of mice that exhibit
      high levels of voluntary wheel-running behavior, as well as various morphological
      and physiological characteristics that cause or allow the elevated locomotor
      activity. Similar experiments could be used to study adaptation to hypoxia.

PMID- 11950134
TI  - Genes, environment, and exercise.
AB  - The definition of the term "environment" has broadened in the past 40 years to
      include knowledge generated from sequencing genes. Studies on animal responses to
      the environment have expanded to include selective lifestyle behaviors.
      Environmental lifestyle components interact with susceptibility genes to pass a
      threshold of biological significance such that a disease requires clinical
      treatment. Examples of environmental-gene interactions producing cystic fibrosis
      and asthma are described. The contributing role of physical inactivity to the
      epidemic of type 2 diabetes is presented with some of its underlying effectors. A
      lack of contractile activity by skeletal muscle is associated with less GLUT4
      protein in the sarcolemma and a lower glucose uptake into the muscle. The
      pathways by which contractile activity signals an increase in glucose uptake
      differs from insulin signaling, but is remarkably similar to how hypoxia
      stimulates muscle to increase its glucose uptake.

PMID- 11950135
TI  - Genetic and environmental adaptation in high altitude natives. Conceptual,
      methodological, and statistical concerns.
AB  - A great number of physiological and anthropological studies have investigated
      Andean and Himalayan populations native to high altitude (HA). A non-scientific
      survey of the extant literature reveals a relatively liberal tradition of
      inferring genetic (evolutionary) adaptation to HA in these groups, often based on
      limited evidence and/or based on study designs insufficient to fully address the
      issue. Rather than review the evidence for or against genetic adaptation, and in
      order to provide some perspective, this paper will review relevant conceptual,
      methodological, and statistical issues that are germane to the study of HA native
      human groups. In particular, focus will be on the limitations of the most common
      research approach which bases evolutionary inference on the comparison of
      phenotypic mean differences between highland and lowland native populations. The
      migrant study approach is discussed, as is a relatively new approach based on
      genetic admixture in hybrid populations.

PMID- 11950136
TI  - Common themes of adaptation to hypoxia. Insights from comparative physiology.
AB  - Many vertebrate animals have superior tolerance to environmental hypoxia compared
      to humans. For example, turtles tolerate an environment of 100% N2 for several
      hours, without apparent ill effect. This hypoxia tolerance is not limited to
      heterotherms, as some species of marine mammals, such as the northern elephant
      seal, may voluntarily dive for periods of up to 2 hours. Torpid bats exhibit
      prolonged periods of apnea and passive diffusion of oxygen down their trachea
      through an open glottis supplies a significant amount of the oxygen uptake. The
      Ruppell's griffon holds the known avian record of flight at 11,278 m, and other
      birds regularly migrate at altitudes over 8000m. These animals exhibit diverse
      adaptations for tolerating their hypoxic environment, many of which are poorly
      understood. Some of theses strategies include 1) the ability to lower metabolic
      rate when exposed to hypoxia 2) the ability to recruit alternate biochemical
      pathways for energy production 3) a left shifted oxy-hemoglobin dissociation
      curve 4) more efficient pulmonary gas exchange 5) the ability to alter blood flow
      distribution under hypoxic stress. Although there are common themes of animal
      adaptation to hypoxic stress, many animal solutions are unique.

PMID- 11950137
TI  - Biology of erythropoietin.
AB  - Hypoxia induces tissue-specific gene products such as erythropoietin (EPO) and
      vascular endothelial growth factor (VEGF), which improve the peripheral O2
      supply, and glucose transporters and glycolytic enzymes, which adapt cells to
      reduced O2 availability. EPO has been the fountainhead in research on pO2
      dependent synthesis of proteins. The EPO gene enhancer (like the flanking DNA
      elements of several other pO2-controlled genes) contains a consensus sequence
      (CGTG) that binds the trans-acting dimeric hypoxia-inducible factor 1 (HIF
      1alpha/beta). The alpha-subunit of HIF-1 is rapidly degraded by the proteasome
      under normoxic conditions, but it is stabilized on occurrence of hypoxia. HIF-1
      DNA-binding is also increased by insulin, and by interleukin-1 and tumor necrosis
      factor. Thus, in some aspects there is synergy in the cellular responses to
      hypoxia, glucose deficiency and inflammation. In viewing clinical medicine
      recombinant human EPO (rHu-EPO) has become the mainstay of treatment for renal
      anemia. Endogenous EPO and rHu-EPO are similar except for minor differences in
      the pattern of their 4 carbohydrate chains. RHu-EPO is also administered to
      patients suffering from non-renal anemias, such as in autoimmune diseases or
      malignancies. The correction of anemia in patients with solid tumors is not
      merely considered a palliative intervention. Hypoxia promotes tumor growth.
      However, the benefits of the administration of rHu-EPO to tumor patients with
      respect to its positive effects on tumor oxygenation, tumor growth inhibition and
      support of chemo- and radiotherapy is still debatable ground.

PMID- 11950138
TI  - Lessons to better understanding of hypoxia sensing. Acquired and congenital
      mutations resulting in polycythemia.
AB  - Adaptation of the organism to hypoxia has profound effect on multiple tissues
      including regulation of erythropoiesis, vasculogenesis, a proper regulation of
      embryogenesis as well as other functions. The elucidation of those congenital or
      acquired mutations giving rise to disease states affecting physiological systems
      devoted to oxygen homeostasis provides not only a practical diagnostic and
      potential therapeutic target, but also allows to identify the essential, non
      redundant physiological pathways that may be hitherto unknown. The erythropoietin
      gene was the first gene expression found to be upregulated by hypoxia; the
      mechanism of this regulation lead to our current understanding of hypoxia
      sensing. Thus it is appropriate that the disorders resulting from augmented
      erythropoiesis are subject of this review.

PMID- 11950139
TI  - Erythropoietin use and abuse: When physiology and pharmacology collide.
AB  - The major function of the erythrocyte is to transport oxygen from the lungs to
      the other tissues, a function ensured by the glycoprotein hormone erythropoietin
      which couples red cell production to long term tissue oxygen requirements. Tissue
      hypoxia is the only physiological mechanism for increasing erythropoietin
      production but there are a variety of mechanisms for its down regulation
      including hyperoxia, increased catabolism by an expanded erythroid progenitor
      cell pool, blood hyperviscosity independently of its oxygen content, renal
      disease and the cytokines produced in inflammatory, infectious and neoplastic
      disorders. Erythropoietin lack results in severe and often transfusion-dependent
      anemia but if bone marrow function is otherwise normal, recombinant human
      erythropoietin therapy can restore the red cell mass and alleviate the
      transfusion need. However, elevation of the red cell mass by recombinant human
      erythropoietin is associated with a reduction in plasma volume and in some
      patients, hypertension is induced. Elevation of the red cell mass is also
      associated with a reduction in cerebral blood flow. When used to gradually
      elevate the hematocrit to 36% in anemic patients, recombinant human
      erythropoietin therapy is usually uneventful. However, when the normal hematocrit
      level is exceeded, the risk for thrombotic events increases since blood viscosity
      varies exponentially with the hematocrit. Increasing the hematocrit by autologous
      blood transfusions can enhance athletic performance in fit individuals and
      recombinant human erythropoietin administration is an obvious surrogate for
      autologous blood transfusions. However, paradoxically, its effects are the
      opposite of those of endurance training, namely a change in red cell mass without
      an increase in the total blood volume. Thus, the use of recombinant human
      erythropoietin as a performance-enhancing agent is dangerous, particularly in the
      less fit athlete, and probably of little benefit in the highly conditioned one.
      Differences in the carbohydrate content of native and recombinant human
      erythropoietin are identifiable by isoelectric focusing, providing a direct means
      for detecting erythropoietin abuse using urine specimens; a panel of surrogate
      blood markers of enhanced erythropoiesis such as soluble transferrin receptors,
      serum erythropoietin, reticulocyte hematocrit and percent macrocytes provide an
      indirect means for this purpose. Timing of surveillance is, of course, critical
      due to biological limitations on the physical presence of the hormone. However,
      education about its dangers may prove to be the most valuable solution to abuse
      of recombinant human erythropoietin for competitive advantage.

PMID- 11950141
TI  - Mountaineering in thin air. Patterns of death and of weather at high altitude.
AB  - An 8000-m peak bring challenges of extremes of hypoxia and weather as well as the
      normal hazards of climbing itself. These challenges have taken a severe toll: 604
      mountaineers have died on those great peaks since 1950. Little is known about
      whether mountain height, use of supplemental oxygen, or team size might influence
      rates of death or of success. However, such information may provide insights not
      only to our understanding of the limits of human performance, but also to
      mountaineers in making decisions on these peaks. We present several examples from
      a research program that is attempting to analyze factors that potentially
      influence success or death rates on the 8K peaks. (1) Apparent risk of death in
      the notorious Khumbu Icefall on Mt. Everest has declined dramatically in recent
      years. This decline could reflect improved route finding and technique, but might
      also reflect climate warming, which has caused the Khumbu glacier to shrink and
      slow in recent decades. (2) Risk of death during descent from an 8000-m peak
      increases with the height of the peak. (3) Risk of death during descent from the
      summit of Everest or of K2 is elevated for climbers not using supplemental
      oxygen. (4) We outline some new studies that are exploring how convective heat
      loss, which influences wind chill, changes with altitude as well as the incidence
      of storms: both factors will impact the probability success and death of
      Himalayan mountaineers.

PMID- 11950140
TI  - Skeletal muscle angiogenesis. A possible role for hypoxia.
AB  - Skeletal muscle is one of the most plastic tissues in the body. Repeated exercise
      causes several muscle adaptations, among which the development of additional
      capillaries (angiogenesis) is prominent. Conversely, inactivity and some chronic
      diseases result in loss of muscle capillaries. Since (endurance) exercise depends
      on adequate O2 supply, it is reasonable to hypothesize that hypoxia occurring
      within muscle during exercise may provide the stimulus to angiogenesis. However,
      there are other potential stimuli including physical effects of increased muscle
      blood flow, or of muscle contraction; release of molecules such as NO that could
      transcriptionally activate angiogenic growth factors; and perhaps changes in the
      biochemical milieu of the muscle cell such as acidosis. This brief review will
      address evidence collected to date mostly at the molecular biological level that
      does in fact implicate reduced intracellular PO2 as a major stimulus to the
      angiogenic process resulting from exercise. In particular, it is shown that VEGF
      message and protein are increased in muscle with exercise, more so in hypoxia,
      and that HIF-1alpha correlates with VEGF as would be expected if hypoxia were the
      major stimulus. In addition, we show that muscle intracellular PO2 falls to very
      low levels during exercise (3-4 Torr), providing a degree of hypoxia compatible
      with a strong role for low PO2 in angiogenic growth factor response. However, the
      definitive experiments using acute gene manipulation to establish a cause and
      effect relationship between hypoxia and muscle angiogenesis remain to be
      performed.

PMID- 11950142
TI  - Weight loss at high altitude.
AB  - Loss of appetite and weight are frequently observed at altitudes above 5000 m.
      However, the pathophysiology behind changes in body composition at extreme
      altitude is still not fully understood. Proper acclimatization to altitude and
      high caloric intake minimizes, but can not completely prevent significant weight
      loss under the influence of hypobaric hypoxia. The discovery of leptin in 1994
      has initiated a new research area investigating molecular networks that connect
      peripheral organs with the central nervous system to sense and regulate energy
      intake as well as energy expenditure. Since then, a whole microcosm of new
      hormones, neurotransmitters and receptors has been discovered and studied with
      respect to body weight control. Those agents include neuropeptide Y (NPY), agouti
      related protein (AGRP), melanocortin receptors (MC-R), cocaine-amphetamine
      regulated transcript (CART), pro-opiomelanocortin (POMC), orexin A and B
      (hypocretins), melanin-concentrating hormone (MCH) and ghrelin (endogenous ligand
      of the growth hormone secretagogue receptor). This overview will introduce the
      current concepts of the molecular control of energy homeostasis and attempt to
      reexamine the effects of altitude on appetite and body composition in light of
      these concepts. An overview of studies on changes of appetite and body
      composition at high altitude will be followed by the presentation of recent data
      on changes of endocrine parameters at hypobaric hypoxia that could be involved in
      the pathophysiology of weight loss.

PMID- 11950143
TI  - The heme oxygenase system and cellular defense mechanisms. Do HO-1 and HO-2 have
      different functions?
AB  - Heme oxygenase isozymes, HO-1, HO-2 and HO-3, are HSP32 protein cognates, with a
      known function of catalyzing the isomer specific oxidation of the heme molecule,
      including that of NO synthase. Unknown until recent years was that the system is
      a central component of the cellular defense mechanisms; this can be attributed to
      a combination of many factors. In biological systems HO activity is responsible
      for production of equimolar amounts of CO, biliverdin and free Fe. The
      serine/threonine kinase, biliverdin reductase, catalyzes reduction of biliverdin
      to bilirubin. Bilirubin is a potent antioxidant and CO is a signal molecule.
      Although both active HO isozymes catalyze the same reaction, HO-1 and HO-2 may
      function in a rather distinct fashion in protection against tissue injury. HO-1
      is the stress responsive cognate that is rapidly induced by free and stable
      radicals as well as by hypoxia. Supra induction of HO-1 completely protects
      ischemic kidney against tissue pathology. This involves rapid inactivation of the
      pro-oxidant heme of denatured hemoproteins and converting it to bilirubin and CO.
      In the case of severe tissue injury, such as compression injury, HO-1 is induced
      and colocalizes with cGMP and pro-apoptotic oncogenes. HO-2, which is the
      constitutive form, in addition to maintaining cell heme homeostasis, inactivates
      NO derived radicals. The isozyme binds the free radical at its "heme regulatory
      motifs" and is "suicide" inactivated at the protein and transcript levels. Data
      are shown that provide evidence for role of the HO system in the cellular defense
      mechanism against free radical-mediated tissue damage, and are consistent with
      the forwarded concept that HO isozymes have common, as well as distinct, roles in
      cellular defense mechanisms.

PMID- 11950144
TI  - Hypoxia-inducible factor in brain.
AB  - HIF-1 is composed of HIF-1alpha and HIF-1beta protein subunits. HIF-1 is induced
      by hypoxia and binds to promoter/enhancer elements and stimulates the
      transcription of hypoxia-inducible target genes. Because HIF-1 activation might
      promote cell survival in hypoxic tissues, we studied the effect of stroke on the
      expression of HIF-1alpha, HIF-1beta and several HIF-1 target genes in adult rat
      brain. After focal cerebral ischemia, mRNAs encoding HIF-1alpha, glucose
      transporter-1 and several glycolytic enzymes including lactate dehydrogenase were
      up-regulated in the areas around the infarction. HIF and its target genes were
      induced by 7.5 hours after the onset of ischemia and increased further at 19 and
      24 hours. Since hypoxia induces HIF in other tissues, systemic hypoxia (6% O2 for
      4.5 h) was also shown to increase HIF-1alpha protein expression in the adult rat
      brain. It is proposed that decreased blood flow to the penumbra decreases the
      supply of oxygen and that this induces HIF-1 and its target genes. Because HIF-1
      activation may promote cell survival in hypoxic tissues, we studied the effect of
      hypoxic preconditioning on HIF-1 expression in neonatal rat brain. Hypoxic
      preconditioning (8% O2/3 hrs), a treatment known to protect the newborn rat brain
      against hypoxic-ischemic injury, markedly increased HIF-1alpha and HIF-1beta
      expression. We also studied the effect of two other known HIF-1 inducers, cobalt
      chloride (CoCl2) and desferrioxamine (DFX), on HIF-1 expression and
      neuroprotection in newborn brain. HIF-1alpha and HIF-1beta protein levels were
      markedly increased after i.p. injection of CoCl2 and DFX. Preconditioning with
      CoCl2 or DFX 24 hours before the stroke decreased infarction by 75% and 56%
      respectively, compared with vehicle-injected, littermate controls. Thus, HIF-1
      activation could contribute to protective brain preconditioning.

PMID- 11950145
TI  - Proton-gated cation channels--neuronal acid sensors in the central and peripheral
      nervous system.
AB  - Metabolic hyperactivity or limited oxygen supply can cause a decrease of tissue
      pH. Severe tissue acidosis that accompanies ischemia and most forms of
      inflammation is painful and sensory neurons respond to acidic tissue pH with
      increased firing. H+-gated cation channels in sensory nerve endings are thought
      to be responsible for the activation of nociceptive afferents by acid. The
      members of one family of recently identified H+-gated cation channels (ASICs,
      Acid Sensing Ion Channels) are candidates for the acid sensor in sensory nerve
      endings. Certain ASIC subunits are also or exclusively expressed in neurons of
      the central nervous system (CNS) where the role of those cation channels is as
      for yet unknown. Neuronal activity is accompanied by pH fluctuations and the
      widespread expression of ASIC channels throughout the CNS suggests that
      activation of those ion channels by local acidic transients might play a role in
      neurotransmission or neuromodulation.

PMID- 11950146
TI  - Structure function relationships of ENaC and its role in sodium handling.
AB  - The epithelial sodium channel (ENaC) in the apical membrane of polarized
      epithelial cells is the rate-limiting step for Na entry into the cell; in series
      with the basolateral Na pump, it allows the vectorial transepithelial transport
      of Na ions. ENaC is expressed in different epithelia like the distal nephron or
      colon, and the airways epithelium. In the lung ENaC controls the composition and
      the amount of pulmonary fluid, whereas in the distal nephron ENaC under the
      control of aldosterone and vasopressin, is essential to adapt the amount of Na+
      reabsorbed with the daily sodium intake. Activating mutations of ENaC cause
      severe disturbances of Na+ homeostasis leading to hypertension in human and in
      mouse models. Functional expression of ENaC in different cell systems allowed the
      identification of structural domains of the protein that are essential for
      channel function and/or modulation of channel activity. Site-directed mutations
      in specific domains of the channel protein lead to channel hyperactivity or
      channel loss of function. Knowledge about ENaC structure-function relationships
      opens new opportunities for development of pharmacological tools for controlling
      ENaC activity, such as channel activators of potential benefit in the treatment
      of pulmonary edema, or highly potent ENaC blockers with natriuretic effects.

PMID- 11950147
TI  - Transepithelial sodium and water transport in the lung. Major player and novel
      therapeutic target in pulmonary edema.
AB  - Active transepithelial transport of sodium from the airspaces to the lung
      interstitium is a primary mechanism driving alveolar fluid clearance. This
      mechanism depends on sodium uptake by amiloride-sensitive sodium channels on the
      apical membrane of alveolar type II cells followed by extrusion of sodium on the
      basolateral surface by the Na-K-ATPase. Injury to the alveolar epithelium can
      disrupt the integrity of the alveolar barrier or downregulate ion transport
      pathways thus reducing net alveolar fluid reabsorption, and enhancing the extent
      of alveolar edema. Endogenous catecholamines upregulate alveolar fluid clearance
      in several experimental models of acute lung injury, but this upregulation is
      short-term and often not sufficient to counterbalance alveolar flooding. There is
      new evidence, however, that pharmacological treatment with beta-adrenergic
      agonists and/or epithelial growth factors may induce a more sustained stimulation
      of alveolar fluid reabsorption and in turn facilitate recovery from experimental
      pulmonary edema. Similar results have been achieved experimentally by gene
      transfer enhancing the abundance of sodium transporters in the alveolar
      epithelium. Clinical studies show that impaired alveolar fluid transport
      mechanisms contribute to the development, severity and outcome of pulmonary edema
      in humans. Very recent data suggest that mechanisms that augment transepithelial
      sodium transport and enhance the clearance of alveolar edema may lead to more
      effective prevention or treatment for pulmonary edema and acute lung injury.

PMID- 11950148
TI  - Is ventilatory acclimatization to hypoxia a phenomenon that arises through
      mechanisms that have an intrinsic role in the regulation of ventilation at sea
      level?
AB  - The purpose of this article is to set out the hypothesis that arterial PO2 may
      play a significant role in the regulation of breathing at sea level. The
      following points are made: 1) Although CO2 is clearly the dominant feedback
      signal in the acute setting, there is evidence, particularly clinical
      observation, that the ventilatory response to CO2 may adapt. 2) Although the
      ventilatory response to an acute variation in alveolar PO2 around sea-level
      values is feeble, studies at altitude have shown that over longer-time periods
      alveolar PO2 is a more powerful regulator of ventilation. 3) Recent evidence
      suggests that mechanisms associated with ventilatory acclimatization to hypoxia
      are active at sea-level values for PO2, and indeed affect the acute ventilatory
      response to hypoxia. 4) While most evidence suggests that the peripheral and
      central chemoreflexes are independent and additive in their contributions to
      ventilation, experiments over longer durations suggest that peripheral
      chemoreceptor afferents may play an important role in regulating central
      chemoreflex sensitivity to CO2. This is potentially an important mechanism by
      which oxygen can alter the acute chemoreflex responses to CO2. In conclusion, the
      mechanisms underlying ventilatory acclimatization to hypoxia may have an
      important role in regulating the respiratory system at sea level.

PMID- 11950149
TI  - Roles of adenosine and nitric oxide in skeletal muscle in acute and chronic
      hypoxia.
AB  - In experiments on anaesthetised rats, the roles played by adenosine and nitric
      oxide (NO) were determined in resting skeletal muscle in acute systemic hypoxia
      and during acclimation to chronic systemic hypoxia. It is concluded that
      adenosine acting on A1 receptors, at least in part in an NO-dependent manner,
      plays essential roles in causing the dilation of proximal and terminal arterioles
      that helps to maintain muscle O2 consumption when O2 delivery is reduced by acute
      systemic hypoxia. It is proposed that adenosine and NO are similarly responsible
      for causing the tonic vasodilation that gradually wanes in the first 7 days of
      chronic hypoxia and that concomitantly, adenosine and hypoxia stimulate VEGF
      expression, so increasing venular permeability and triggering angiogenesis. By 7
      days of chronic hypoxia, arteriolar remodelling is well established and within 18
      21 days, substantial capillary angiogenesis alleviates tissue hypoxia. At this
      time, vasoconstrictor responses to the sympathetic transmitter norepinephrine are
      reduced, but dilator responses to adenosine released by acute hypoxia are
      enhanced, as may be explained by increased sensitivity to NO. Thus, preservation
      of tissue oxygenation is apparently associated with impaired ability to regulate
      arterial pressure and vulnerability to further hypoxia.

PMID- 11950150
TI  - The pVHL-hIF-1 system. A key mediator of oxygen homeostasis.
AB  - Matching oxygen consumption and supply represents a fundamental challenge to
      multicellular organisms. HIF-1 is a transcription complex which is emerging as a
      key mediator of oxygen homeostasis. HIF-1 controls the expression of many genes,
      including erythropoietin, angiogenic growth factors, glucose transporters and
      glycolytic enzymes. The HIF-1 complex, which contains an alpha and beta subunit
      (both basic helix-loop-helix proteins of the PAS family) is formed in hypoxia and
      modulates gene expression through hypoxia response elements. Regulation involves
      ubiquitin-mediated oxygen-dependent destruction of the alpha subunit. Oxygen
      regulated destruction of HIF-alpha requires the von Hippel Lindau tumour
      suppressor protein (pVHL). pVHL acts as the recognition component of a ubiquitin
      E3 ligase complex which binds HIF-alpha. Loss of pVHL function, which results in
      constitutive activation of the hypoxic response, is important in the development
      of clear cell renal cancer, where both copies of the gene are usually
      inactivated. The importance of the VHL-HIF system in multicellular organisms is
      supported by conservation in the nematode C. elegans. Understanding the events
      resulting in HIF activation should provide novel therapeutic targets. This would
      be useful in preventing angiogenesis in cancers and promoting adaptive changes in
      hypoxic/ischaemic tissue.

PMID- 11950151
TI  - Interval hypoxic training.
AB  - Interval hypoxic training (IHT) is a technique developed in the former Soviet
      Union, that consists of repeated exposures to 5-7 minutes of steady or
      progressive hypoxia, interrupted by equal periods of recovery. It has been
      proposed for training in sports, to acclimatize to high altitude, and to treat a
      variety of clinical conditions, spanning from coronary heart disease to Cesarean
      delivery. Some of these results may originate by the different effects of
      continuous vs. intermittent hypoxia (IH), which can be obtained by manipulating
      the repetition rate, the duration and the intensity of the hypoxic stimulus. The
      present article will attempt to examine some of the effects of IH, and, whenever
      possible, compare them to those of typical IHT. IH can modify oxygen transport
      and energy utilization, alter respiratory and blood pressure control mechanisms,
      induce permanent modifications in the cardiovascular system. IHT increases the
      hypoxic ventilatory response, increase red blood cell count and increase aerobic
      capacity. Some of these effects might be potentially beneficial in specific
      physiologic or pathologic conditions. At this stage, this technique appears
      interesting for its possible applications, but still largely to be explored for
      its mechanisms, potentials and limitations.

PMID- 11950152
TI  - Leukocyte-endothelial interactions in environmental hypoxia.
AB  - Hypoxia induced by reducing inspired PO2 (PIO2) to 70 Torr, promotes a rapid
      microvascular response characterized by increased leukocyte rolling and adherence
      to the venular endothelium, leukocyte emigration to the perivascular space and
      increased vascular permeability. This appears to be a generalized response since
      it is observed in venules of the mesentery, cremaster muscle and pial
      microcirculations. After three weeks of acclimatization to hypoxia (barometric
      pressure 380 Torr, PIO2 70 Torr), the initial microvascular response resolves and
      exposure to even lower PIO2 (50 Torr) fails to elicit a microvascular response.
      The initial response is accompanied by a reversible increase in the generation of
      reactive oxygen species (ROS) and is blocked by antioxidants and by interventions
      that increase the tissue levels of nitric oxide (NO). In contrast to
      ischemia/reperfusion, ROS levels increase during hypoxia and return towards pre
      hypoxic values after return to normoxia. Acclimatization involves upregulation of
      inducible NO synthase (iNOS): inhibition of iNOS using two different antagonists
      results in increased leukocyte-endothelial interactions and increased ROS
      generation. The results suggest that hypoxia initially leads to an alteration of
      the ROS/NO balance which is eventually restored during the acclimatization
      process. This phenomenon may have relevance to the microcirculatory alterations
      associated with hypoxic exposure, including acute mountain sickness and high
      altitude pulmonary and cerebral edema.

PMID- 11950153
TI  - Gene transfer and metabolic modulators as new therapies for pulmonary
      hypertension. Increasing expression and activity of potassium channels in rat and
      human models.
AB  - Chronic Hypoxic Pulmonary Hypertension (CH-PHT) is characterized by pulmonary
      artery (PA) vasoconstriction and cell proliferation/hypertrophy. PA smooth muscle
      cell (PASMC) contractility and proliferation are controlled by cytosolic Ca++
      levels, which are largely determined by membrane potential (E(M)). E(M) is
      depolarized in CH-PHT due to decreased expression and functional inhibition of
      several redox-regulated, 4-aminopyridine (4-AP) sensitive, voltage-gated K+
      channels (Kv1.5 and Kv2.1). Humans with Pulmonary Arterial Hypertension (PAH)
      also have decreased PASMC expression of Kv1.5 and Kv2.1. We speculate this "K+
      channelopathy" contributes to PASMC depolarization and Ca++ overload thus
      promoting vasoconstriction and PASMC proliferation. We hypothesized that
      restoration of Kv channel expression in PHT and might eventually be beneficial.
      METHODS: Two strategies were used to increase Kv channel expression in PASMCs:
      oral administration of a metabolic modulator drug (Dichloroacetate, DCA) and
      direct Kv gene transfer using an adenovirus (Ad5-Kv2.1). DCA a pyruvate
      dehydrogenase kinase inhibitor, promotes a more oxidized redox state mimicking
      normoxia and previously has been noted to increase K+ current in myocytes. Rats
      were given DCA in the drinking water after the development of CH-PHT and
      hemodynamics were measured approximately 5 days later. We also tested the ability
      of Ad5-Kv2.1 to increase Kv2.1 channel expression and function in human PAs ex
      vivo. RESULTS: The DCA-treated rats had decreased PVR, RVH and PA remodeling
      compared to the control CH-PHT rats (n=5/group, p<0.05). DCA restored Kv2.1
      expression and PASMC Kv current density to near normoxic levels. Adenoviral gene
      transfer increased expression of Kv2.1 channels and enhanced 4-AP constriction in
      human PAs. CONCLUSION: Increasing Kv channel function in PAs is feasible and
      might be beneficial.

PMID- 11950154
TI  - Chronic mountain sickness. A view from the crow's nest.
AB  - Chronic mountain sickness (CMS) is a poorly understood syndrome, characterized by
      hypoxemia and polycythemia and occurring in persons residing at high altitude. To
      better characterize the disorder, we have reviewed measurements in more than 750
      men and 200 women living at altitude as published and as submitted by colleagues.
      In men, blood hemoglobin concentration (Hb) and arterial oxygen saturation (SaO2)
      related to altitude (r=0.72). There was greater variability in both SaO2 and
      hemoglobin above than below 3000 m, largely due to inter-individual variations in
      effective ventilation. For the entire cohort, a linear relationship (r=0.72) of
      an index of hematopoietic response (Hb) to an index of stimulus (SaO2) was
      independent of age, altitude, duration of altitude residence greater than one
      year, ethnic origin, geographic location, presence or absence of CMS and nearly
      independent of gender. A potentially important and usually unrecognized variation
      in the hypoxic stimulus was desaturation during sleep. Contributions to variation
      in response include ingested toxins, such as cobalt, and nutritional
      deficiencies, including iron. Pulmonary hypertension was related to chronic
      hypoxia, with an uncertain contribution from polycythemia. In CMS there were
      profound hypoxemia at night, decrease in cerebral blood flow, and loss of
      cerebral blood flow regulation, possibly causing the cerebral symptoms. We
      speculate that the relationship of Hb to SaO2 is more useful than of hemoglobin
      to altitude, that hypoventilation awake and asleep are the primary causes
      accentuating altitude-hypoxia, and that the brain is the primary target organ in
      the disorder.

PMID- 11950155
TI  - Hypoxia training for sea-level performance. Training high-living low.
AB  - It is widely accepted that prolonged exposure to extreme altitude is detrimental
      for exercise performance and muscle structure. Moreover, highly trained subjects
      seem to suffer more under hypoxic conditions than untrained people. When using
      hypoxia as an ergogenic stimulus in athletes, it has thus become customary to
      limit hypoxia exposure in terms of altitude and duration of exposure in order to
      achieve defined physiologic goals. If hypoxia application is limited to the
      duration of training sessions, specific hypoxia responses on the molecular level
      in skeletal muscle tissue can be demonstrated. Hypoxia inducible factor 1 (HIF
      1alpha mRNA) is upregulated after 6 weeks of endurance training in hypoxia
      (equivalent to an altitude of 3850 m) in previously untrained subjects. This
      upregulation is independent of training intensity but not observed in subjects
      training under similar conditions in normoxia. High intensity training in hypoxia
      further results in an increase of vascular endothelial growth factor (VEGF) mRNA,
      capillarity and myoglobin mRNA. These results suggest that hypoxia training
      results in improvements of the oxygen transfer capacity in skeletal muscle
      tissue. They thus offer a plausible explanation for the observation that effects
      of hypoxia training in athletes can best be demonstrated when performance tests
      are carried out in hypoxia. Beneficial effects of "training high-living low" for
      sea level performance of athletes can be inferred from the structural changes
      observed in muscle tissue; however, the functional improvements remain to be
      demonstrated directly.

PMID- 11950156
TI  - Genetic lessons from high altitude.
AB  - What lessons can we learn from mountain sickness or wellness that may apply to
      our patients? Does hypoxia affect us similarly regardless of its cause? Millions
      of individuals are as hypoxic from congenital or acquired heart or lung disease
      as healthy individuals may be at altitude. Certain adjustments enable many of
      such patients to lead nearly normal lives. I will compare their adjustments to
      those seen in the acclimatization of healthy persons to altitude. Some living
      organisms use strategies which enable them to tolerate a degree of hypoxia lethal
      to man. Are there lessons we can learn from them? In my short talk I will raise a
      few provocative questions, and these will lead me to discuss the relevance of
      basic research to the resolution of vexing human ailments. When does
      commercialization of research become a form of intellectual prostitution?

PMID- 11950158
TI  - Update: High altitude pulmonary edema.
AB  - Recent high altitude studies with pulmonary artery (PA) catheterization and
      broncho-alveolar lavage (BAL) in early high altitude pulmonary edema(HAPE) have
      increased our understanding of the pathogenetic sequence in HAPE. High preceding
      PA and pulmonary capillary pressures lead to a non-inflammatory leak of the
      alveolar-capillary barrier with egress of red cells, plasma proteins and fluid
      into the alveolar space. The mechanisms accounting for an increased capillary
      pressure remain speculative. The concept that hypoxic pulmonary vasoconstriction
      (HPV) is uneven so that regions with less vasoconstriction are over-perfused and
      become edematous remains compelling but unproved. Also uncertain is the role and
      extent of pulmonary venoconstriction. With disruption of the normal alveolar
      capillary barrier, some individuals may later develop a secondary inflammatory
      reaction. A high incidence of preceding or concurrent respiratory infection in
      children with HAPE has been used to support a causative role of inflammation in
      HAPE. However, alternatively even mild HPV may simply lower the threshold at
      which inflammation-mediated increases in alveolar capillary permeability cause
      significant fluid flux into the lung. Other major questions to be addressed in
      future research are: 1.) What is the mechanism of exaggerated hypoxic pulmonary
      vasoconstriction? Is there a link to primary pulmonary hypertension? Several
      observations suggest that susceptibility to HAPE is associated with endothelial
      dysfunction in pulmonary vessels. This has not yet been studied adequately. 2.)
      What is the nature of the leak? Is there structural damage, i. e. stress failure,
      or does stretch cause opening of pores? 3.) What is the pathophysiologic
      significance of a decreased sodium and water clearance across alveolar epithelial
      cells in hypoxia? 4.) What is the role of exercise? Do HAPE-susceptible
      individuals develop pulmonary edema when exposed to hypoxia without exercise?
      Answers to these questions will increase our understanding of the pathophysiology
      of HAPE and also better focus research on the genetic basis of susceptibility to
      HAPE.

PMID- 11950157
TI  - The effects of altitude training are mediated primarily by acclimatization,
      rather than by hypoxic exercise.
AB  - For training at altitude to be effective, it must provide some advantage above
      and beyond similar training at sea level. This advantage could be provided by: 1)
      acclimatization to altitude which improves oxygen transport and/or utilization;
      2) hypoxic exercise which "intensifies" the training stimulus; or 3) some
      combination of both. Controlled studies of "typical" altitude training, involving
      both altitude acclimatization and hypoxic exercise have never been shown to
      improve sea level performance. This failure has been attributed to reduced
      training loads at altitude. One approach developed by Levine and Stray-Gundersen,
      called "living high-training low" has been shown to improve sea level performance
      over events lasting 8-20 minutes. This strategy combines altitude acclimatization
      (2,500 m) with low altitude training to get the optimal effect. The opposite
      strategy, "living low-training high" is proposed by Dr. Hoppeler in this debate.
      In defense of the primacy of the altitude acclimatization effect, data will be
      presented to support the following: 1). Living high-training low clearly improves
      performance in athletes of all abilities; 2). The mechanism of this improvement
      is primarily an increase in erythropoietin leading to increased red cell mass,
      VO2max, and running performance; 3). Rather than intensifying the training
      stimulus, training at altitude leads to the opposite effect--reduced speeds,
      reduced power output, reduced oxygen flux--and, following the principal of
      symmorphosis, is not likely to provide any advantage for a well trained athlete;
      4). At the moderate altitudes used by most athletes, resting oxygen delivery to
      skeletal muscle is well preserved, arguing against any detrimental effect on
      "protein synthesis"; 5). It is possible however, that at significantly higher
      altitudes, acclimatization leads to appetite suppression, inhibition of protein
      synthesis, muscle wasting, excessive ventilatory work, and metabolic compensation
      that is NOT advantageous for a competitive athlete.

PMID- 11950159
TI  - Recovery of injured adrenal medulla by differentiation of pre-existing
      undifferentiated chromaffin cells.
AB  - We described previous that the adrenal medulla recovers rapidly from the injuries
      due to salinomycin. In the present study we found the recovery to be apparently
      due to differentiation of pre-existing, primitive undifferentiated, chromaffin
      cells, rather than mitosis, as evidenced by lack of incorporation of 5-bromo-2
      deoxyuridine in the differentiating and/or differentiated chromaffin cells.
      Electron-dense, striated fibrils observed within the necrotic cells and in the
      extracellular space were presumed to be intermediate degradation products.
      Schwann cells actively functioned as phagocytes in this study, and seemed to
      indirectly stimulate the differentiation of undifferentiated chromaffin cells.

PMID- 11950160
TI  - Enhancing effects of oltipraz on the development of spontaneous hepatic lesions
      in LEC rats.
AB  - Oltipraz, developed as an antischistosomal agent, protects against the
      hepatotoxicity of many xenobiotics and is known to be an effective inhibitor of
      experimental carcinogenesis in rodents. In the present study, we investigated its
      effects on the development of lesions in LEC rats, established as a mutant strain
      characterized by a hereditary predisposition for hepatic damage with severe
      jaundice. A total of 35 male 6-week-old LEC rats were divided into 2 groups, one
      administered diet supplemented with oltipraz at a dose of 400 ppm, and the other
      fed basal diet alone. Animals in each group were sequentially sacrificed at 10,
      15, and 25 weeks after commencement of the oltipraz administration. Eight animals
      died or became moribund in the oltipraz group during weeks 10 and 11 of the
      treatment, whereas only one rat in the nontreatment group died after 16 weeks.
      All dead or moribund animals showed severe or moderate jaundice. The treatment
      caused a decrease in body weight gain from 9 to 13 weeks, and an increase in
      relative liver weight at each sacrifice point. Serum biochemical assays performed
      at week 25 revealed elevated levels of serum AST, ALT, LDH, ALP, gamma-GTP, and
      Cu in the treated-animals. The glutathione level in the livers of oltipraz
      treated animals was significantly higher than that in the control rats.
      Histopathologically, enlarged hepatocytes with large nuclei, focal necrosis,
      pigment granule-laden Kupffer cells and hypertrophy of renal tubule cells were
      observed in both groups, but the severity of these changes was greater in the
      oltipraz group. Our results thus indicate that spontaneous hepatic damage in LEC
      rats is enhanced by oltipraz, by a mechanism that remains to be elucidated.

PMID- 11950161
TI  - Lysosomal-storage disorder induced by elmiron following 90-days gavage
      administration in rats and mice.
AB  - Elmiron, a highly sulfated, semisynthetic pentose polysaccharide with properties
      similar to heparin, is used for the treatment of interstitial cystitis. Thirteen
      week gavage studies were conducted by administering the drug in deionized water
      to F344/N rats and B6C3F1 mice once daily, 5 days per week for up to 13
      consecutive weeks, at doses of 0, 63, 125, 250, 500, and 1,000 mg/kg body weight.
      No significant drug-related effects were observed in body weight, survival,
      clinical, and necropsy results. Significant organ weight increases were seen in
      the liver, lungs, and spleen of both species and the kidneys of rats, mainly in
      groups treated with 250 mg/kg/day and above. Hematological analysis indicated
      increases for both species in the white blood cell and lymphocyte counts. Sites
      of toxicity identified histopathologically were the rectum, liver, mesenteric and
      mandibular lymph nodes (both sexes), spleen (mice only), and lungs and kidneys
      (rats only). Lesions consisted mainly of infiltration into multiple tissues of
      vacuolated histiocytes, which, by histochemical investigation, indicated the
      presence of neutral and acidic mucins and lipidic material within the vacuoles.
      Transmission electron microscopy identified these vacuoles as lysosomal
      structures that exhibited a variety of contents. On the basis of our findings, we
      propose that Elmiron was absorbed through the focally disrupted rectal mucosa,
      was deposited in the lamina propria, accumulated within macrophages, and then was
      distributed by these cells or as a free chemical via the lymphatics and blood, to
      the various organ sites manifesting histiocytic infiltration. The cytoplasmic
      membrane-bound structures within macrophages were lysosomes containing membranous
      material of cellular origin and, perhaps, remnants of the deposited test
      material, Elmiron.

PMID- 11950162
TI  - Assessment of carcinogenicity of di(2-ethylhexyl)phthalate in a short-term assay
      using Xpa-/- and Xpa-/-/p53+/- mice.
AB  - The potential of Xpa-/- and Xpa-/-/p53+/- mice for short-term carcinogenicity
      assays was evaluated with di(2-ethylhexyl)phthalate (DEHP). Groups of 15 male and
      female Xpa-/- mice, received diets containing 0, 1, 500, 3,000, or 6,000 ppm
      DEHP, and wild-type (WT) and Xpa-/-p53+/-mice 0 or 6,000 ppm DEHP for 39 weeks.
      Xpa-/-, Xpa-/-/p53+/-, and WT males, fed 2,500 ppm p-cresidine, served as a
      positive control. In all models, the survival was not altered by DEHP. Increased
      incidences of nonneoplastic lesions were recorded in testes and kidneys with no
      apparent difference between the models. The only liver tumors in all models were
      adenomas in males with no statistically significantly increased incidence. For p
      cresidine. the survival was decreased (p < 0.05) only in transgenic models.
      Statistically significantly increased incidences of nonneoplastic lesions were
      recorded in the liver, urinary bladder, and nasal cavity in all models, and in
      kidneys in transgenic models. The only tumors with statistically significantly
      increased incidence were liver adenomas in transgenic models (XPA: I vs 7:
      'XPA/p53': 0 vs 12; WT: 0 vs 5, p = 0.053) and urinary bladder carcinomas in
      XPA/p53 model (0 vs 7). The negative carcinogenic response to DEHP and the
      positive response to p-cresidine support the expected sensitivity to genotoxic
      carcinogens in these transgenic models.

PMID- 11950163
TI  - Olfactory mucosal necrosis in male CD rats following acute inhalation exposure to
      hydrogen sulfide: reversibility and the possible role of regional metabolism.
AB  - Hydrogen sulfide (H2S) is a potent inhibitor of cytochrome oxidase (CO) and is
      associated with dysosmia and anosmia in humans and nasal lesions in exposed
      rodents. An improved understanding of the pathogenesis of these lesions is needed
      to determine their toxicological relevance. We exposed 10-week-old male CD rats
      to 0, 30, 80, 200, or 400 ppm H2S for 3 hours/day for 1 or 5 days consecutively.
      The nose was histologically examined 24 hours after H2S exposure, and lesion
      recovery was assessed at 2 and 6 weeks following the 5-day exposure. A single 3
      hour exposure to > or = 80 ppm H2S resulted in regeneration of the respiratory
      mucosa and full thickness necrosis of the olfactory mucosa localized to the
      ventral and dorsal meatus, respectively. Repeated exposure to the same
      concentrations caused necrosis of the olfactory mucosa with early mucosal
      regeneration that extended from the dorsal medial meatus to the caudal regions of
      the ethmoid recess. Acute exposure to 400 ppm H2S induced severe mitochondrial
      swelling in sustentacular cells and olfactory neurons, which progressed to
      olfactory epithelial necrosis and sloughing. CO immunoreactive cells were more
      frequently observed in regions of the olfactory mucosa commonly affected by H2S
      than in regions that were not. These findings demonstrate that acute exposure to
      >80 ppm H2S resulted in reversible lesions in the respiratory and olfactory
      mucosae of the CD rat and that CO immunoreactivity may be a susceptibility factor
      for H2S-induced olfactory toxicity in the rat.

PMID- 11950164
TI  - Distribution of inorganic mercury in liver and kidney of beluga and bowhead
      whales through autometallographic development of light microscopic tissue
      sections.
AB  - Inorganic mercury was localized through autometallography (AMG) in kidney and
      liver of free-ranging, subsistence-harvested beluga (Delphinapterus leucus: n =
      20) and bowhead (Balaena mysticetrus: n = 5) whales. AMG granules were not
      evident in bowhead tissues, confirming nominal mercury (Hg) concentrations (range
      = 0.011 to 0.038 microg/g ww for total Hg). In belugas, total Hg ranged from 0.30
      to 17.11 and from 0.33 to 82.47 microg/g ww in liver and kidney, respectively.
      AMG granules were restricted to cortical tubular epithelial cytoplasm in belugas
      with lower tissue burdens; whales with higher tissue burdens had granules
      throughout the uriniferous tubular epithelium. In liver, AMG granular densities
      differed between lobular zones, concentrating in stellate macrophages and bile
      cannalicular domains of hepatocytes. AMG granules aggregated in periportal
      regions in belugas with lower hepatic Hg concentrations, yet among whales with
      higher Hg, AMG granule deposition extended to pericentral and midzonal regions of
      liver lobules. Mean areas occupied by AMG granules correlated well with hepatic
      Hg concentrations and age. In beluga livers, AMG staining density was not
      associated with lipofuscin quantity (an index of oxidative damage). Occasionally,
      AMG granules and lipofuscin were colocalized, but more often were not, implying
      that Hg was not a prominent factor in hepatic lipofuscin deposition in belugas.

PMID- 11950165
TI  - Cystic degeneration/Spongiosis hepatis in rats.
AB  - Cystic degeneration/spongiosis hepatis in rats has been proposed to be a
      preneoplastic and/or neoplastic lesion by some authors, because of its
      proliferative properties and persistent increased cell turnover rate in stop
      experiments using hepatocarcinogens, and the assumption that it can develop into
      a sarcoma. The neoplastic potential of cystic degeneration is questioned in this
      review article. Cystic degeneration, which appears to derive from altered Ito
      cells, does not have neoplastic histomorphologic characteristics, although it may
      be composed of cells with an increased mitotic index. In this regard, persistent
      proliferation is also seen with other nonneoplastic lesions. Arguments are
      presented to show that the induced, probably extremely rare sarcoma that was
      associated with cystic degeneration most likely derives from the very rare
      induced spherical Ito-cell aggregate with an unusually high cellular turnover
      rate in rats treated with hepatocarcinogens, and not from cystic degeneration.
      Also, in none of 12 referenced standard oncogenicity studies with chemically
      induced cystic degeneration was the lesion associated with mesenchymal (Ito-cell)
      tumors. Consequently, evidence is lacking that cystic degeneration in rats should
      be classified as a preneoplastic or neoplastic lesion. The 12 oncogenicity
      studies in rats with induced cystic degeneration showed a marked sex
      predilection, with males more likely to develop either spontaneous or chemically
      induced lesions. In these 12 studies, cystic degeneration was more often
      associated with hepatocellular hypertrophy or hepatotoxicity. rather than
      hepatocarcinogenicity. Thus, it is concluded that hepatocarcinogens induce cystic
      degeneration, not because they are carcinogenic. but because they have other
      effects on the liver, and that cystic degeneration may be a secondary/reparative
      change. Cystic degeneration in fish parallels the situation in rats in many
      respects, yet the existence of the lesion in other species, including man, is not
      as well supported. Based on the data presented in this review, spontaneous and
      induced cystic degeneration in rats and fish is not a preneoplastic or neoplastic
      lesion and risk assessment for man can be based on no-effect levels and safety
      margins, as for other nonneoplastic adverse effects that have no counterpart in
      man.

PMID- 11950166
TI  - Spontaneous lesions in control B6C3F1 mice and recommended sectioning of male
      accessory sex organs.
AB  - Because sampling of the paired lobes (ventral, dorsal, lateral, and anterior) of
      the mouse prostate has often been inconsistent, comparisons among different
      investigations have lacked validity. The absence of site identification for
      prostatic lesions has made reported incidences relatively nonspecific. We present
      here the lobe-specific incidences and degree of severity of spontaneous lesions
      in prostate, coagulating gland (anterior prostatic lobe), seminal vesicles, and
      ampullary glands in 612 control B6C3F1 mice from 12 recent National Toxicology
      Program 2-year carcinogenicity and toxicity studies conducted in 1 of 4 different
      laboratories. Lymphocytic infiltration, inflammation, epithelial hyperplasia,
      mucinous cyst, and mucinous metaplasia were observed in the dorsolateral lobes.
      Lymphocytic infiltration, inflammation, epithelial hyperplasia, and edema were
      present in the ventral lobes. Lymphocytic infiltration, acinar dilatation,
      inflammation, epithelial hyperplasia, and atrophy occurred in the coagulating
      glands. No neoplastic lesions were observed in the prostate or coagulating gland.
      Lymphocytic infiltration, acinar dilatation, inflammation, atrophy, adenoma,
      adenocarcinoma, and a granular cell tumor were observed in the seminal vesicles.
      Lymphocytic infiltration was also present in the ampullary glands. The results of
      our survey indicate that the amounts of glandular tissues were not present
      consistently in slides from the different laboratories. Landmarks for uniform
      tissue trimming are needed. We therefore suggest an optimal trimming and
      embedding method for mouse prostate and seminal vesicles to ensure adequate,
      consistent sampling.

PMID- 11950167
TI  - Biochemical and morphological events during okadaic acid-induced apoptosis of
      Tsc2-null ERC-18 cell line.
AB  - Several tumor suppressor genes have been shown to regulate cellular
      susceptibility to proliferation or apoptotic cell death. An essential first step
      in studies with the long-range goal of determining the effect of a tumor
      suppressor gene on cellular susceptibility to apoptosis is careful
      characterization of the cell's response to an apoptotic stimulus. The goals of
      this study were to characterize the apoptotic response of a tuberous sclerosis
      complex-2 (Tsc2) tumor suppressor gene-null cell line, to establish valid
      biochemical events that can be used as apoptosis markers, and to determine how
      these events correlate with apoptosis-specific morphologic changes. For
      characterization of apoptosis, we treated Tsc2-null renal epithelial tumor cells
      (ERC-18) with okadaic acid (OKA, 0.1-0.25 microM), and measured the biochemical
      and morphologic events during the apoptotic response. Electron microscopic and
      immunocytochemical evaluation showed an early loss of microvilli and a loss of
      vinculin and talin staining from focal adhesions within 1 hour. During the first
      2 hours of treatment with 0.25 microM OKA, ERC-18 cells rounded and approximately
      50% detached from the culture vessel with minimal membrane bleb formation.
      Phosphatidylserine externalization, chromatin margination and fragmentation,
      cytochrome C release, and caspase-3 and -7 cleavage were evident at 6 hours.
      Maximal membrane bleb formation occurred between 6 and 10 hours. Cells progressed
      to secondary oncotic necrosis between 10 and 24 hours of OKA treatment. Almost
      all cells had an oncotic phenotype after 24 hours, and 17.5% lost cell membrane
      integrity. A small subpopulation (< or = 5%) of OKA-treated cells underwent
      primary oncotic necrosis within 6 hours. Interestingly, the caspase-3 and -7
      inhibitor Z-DEVD-FMK did not inhibit or delay OKA-induced apoptosis in these
      cells. Our results suggest a complex apoptotic model involving 2 or more
      potentially parallel death pathways. Although caspase-3 and -7 cleavage occurs
      during apoptosis in this model, this cleavage may not independently regulate cell
      death in ERC-18 cells. Therefore, measurement of apoptosis in this model requires
      analysis of both biochemical and morphologic events.

PMID- 11950168
TI  - Species differences in the distribution of drug-metabolizing enzymes in the
      pancreas.
AB  - We investigated the cellular expression of 9 cytochrome P450-isozymes (CYP1A1,
      CYPIA2, CYP2B6, CYP2C8,9,19, CYP2D1, CYP2E1, CYP3A1, CYP3A2, CYP3A4) and 3
      glutathione S-transferase-isozymes (GST-pi, GST-alpha. GST-mu) in the pancreas of
      hamsters, mice, rats, rabbits, pigs, dogs and monkeys, and in comparison with the
      human pancreas. A wide variation was found in the cellular localization of these
      enzymes between the 8 species. Most enzymes were expressed in the pancreas of the
      hamster, mouse, monkey and human, whereas rats, pigs, rabbits and dogs were
      lacking several isozymes. However, in all of the species the islet cells
      expressed more enzymes than ductal and acinar cells. An exclusive expression of
      enzymes in the islet cells was found in the hamster (CYP2E1). mouse (CYP1A1 ,
      CYP1A2, GST-alpha, GST-mu), rat (CYP2C8,9, 19). rabbit (CYP1A2, CYP2B6, GST-pi),
      and pig (CYP1AI). Although no polymorphism was found in the pancreas of animals,
      in human tissue four enzymes were missing in about 50% of the cases. The results
      imply a greater importance of the islet cells in the metabolism of xenobiotics
      within the pancreas. The differences in the distribution of these drug
      metabolizing enzymes in the pancreas between the species call for caution when
      extrapolating experimental results to humans.

PMID- 11950169
TI  - Renal pathology in hemizygous sickle cell mice.
AB  - Transgenic mice have been developed that express exclusively human sickle cell
      beta hemoglobin and have major pathological features found in humans with sickle
      cell disease. These mice provide a unique opportunity to investigate the
      fundamental mechanisms of this disease and to design new strategies to correct
      the associated genetic defect(s). We found that in breeding males expressing only
      adult human alpha-globin and sickle beta-globin (homozygous SS mice) with females
      containing these transgenes plus one copy of the mouse beta-globin gene
      (hemizygous SS mice) greater than expected numbers of hemizygous offspring were
      produced than homozygous mice (carrying no mouse beta-globin gene). These
      hemizygous mice, expressing the human alpha and sickle beta(s) transgenes in
      combination with mouse beta+/-, were used for our preliminary studies of their
      renal pathology. No kidney lesions were found in the control (129/Sv) mice,
      whereas about 50% of the hemizygous SS mice showed mild-to-severe kidney lesions,
      including glomerulonephritis, cystic atypical hyperplastic tubules, and general
      nephropathy. Kidneys of some hemizygous mice were normal or showed minimal
      nephropathy, yet those of the susceptible phenotype developed a mild-to-more
      severe form of renal lesions. The tubular epithelium of kidneys of hemizygous
      mice of the more affected phenotype exhibited increased expression of inducible
      nitric oxide synthase with an increased 3-nitrotyrosine in close proximity. There
      was also a stronger immunostaining for vascular cell adhesion molecule-1 in the
      interstitial capillary cells as well as the tubular epithelial cells of the renal
      cortex, compared with normal control mice. The occurrence of a high incidence of
      renal abnormalities in our hemizygous SS mice suggests that these mice may
      provide a suitable model to study the pathogenesis of nephropathy resulting from
      altered blood flow and/or insufficient oxygen delivery.

PMID- 11950170
TI  - Association of adrenal pheochromocytoma and lung pathology in inhalation studies
      with particulate compounds in the male F344 rat--the National Toxicology Program
      experience.
AB  - Systemic hypoxemia, occurring in space-occupying lung pathologies such as
      inflammation and neoplasms. reduces the gas exchange area and stimulates
      catecholamine secretion from the adrenal medulla where chronic endocrine
      hyperactivity may lead to hyperplasia and neoplasia. We investigated the possible
      correlation between nonneoplastic chronic pulmonary lesions and adrenal
      pheochromocytoma in 9 recent, NTP, 2-year particulate inhalation studies in male
      F344 rats. Re-evaluation for chronic active inflammation, interstitial fibrosis,
      alveolar epithelial hyperplasia, squamous metaplasia, proteinosis, and
      histiocytosis revealed significant associations of pheochromocytoma only with the
      severity of inflammation and fibrosis. Nickel oxide, cobalt sulfate, indium
      phosphide, talc, and nickel subsulfide studies showed chemical-related incidences
      of adrenal pheochromocytoma and significant (p < 0.01) associations with
      inflammation and fibrosis. Gallium arsenide, vanadium pentoxide, molybdenum
      trioxide, and nickel sulfate hexahydrate studies revealed an increased incidence
      and/or severity of nonneoplastic lung lesions, but no increased incidence of
      pheochromocytoma. Although gallium arsenide and molybdenum trioxide showed no
      dose-related increase in pheochromocvtoma, a significant (p < 0.01) correlation
      of the latter with the severity of fibrosis and inflammation occurred. In the
      vanadium pentoxide and nickel sulfate hexahydrate studies, no relationship
      between nonneoplastic lung lesions and pheochromocytoma was manifested. Our
      investigation assessed the strength of these various associations and supports
      the possible roles of 2 chronic pulmonary lesions-fibrosis and inflammation-and
      hypoxemia in the induction of pheochromocytoma in the F344 male rat.

PMID- 11950171
TI  - Pregnancy dating in the rat: placental morphology and maternal blood parameters.
AB  - The rat is commonly used as a model in studies on embryology and reproduction
      toxicology. Surprisingly, the current literature does not provide a comprehensive
      reference data set on placental development in rat. Therefore, we have evaluated
      morphological changes of the placenta and maternal blood parameters during
      pregnancy of the Sprague-Dawley rat. The morphologic data presented in this study
      may be useful as reference material. This study revealed that placental
      development in the rat is a well-defined process, characterized by key
      synchronized morphological events at specific points in time, convenient for
      laboratory practice and provides the toxicologist with a sensitive tool to
      distinguish between normal and abnormal placental development and to detect fetal
      and placental mismatches. During rat pregnancy, significant changes were observed
      in maternal blood parameters strongly reminiscent of those observed in pregnant
      women. These changes included: (a) decreased blood cell volume as a result of
      hemodilution, (b) increased white blood cell counts reflecting the response of
      the mother to the fetal allograft, (c) increased blood clotting values, (d)
      decreased plasma glucose and increased lipid content maximizing fetal glucose
      availability and maternal energy conservation, and (e) decreased electrolyte
      values reflecting plasma volume expansion. It was concluded that the combined
      data set on placental morphology and maternal blood parameters in pregnant rats
      provides powerful tools for recognition of abnormal pregnancies.

PMID- 11950172
TI  - New tools in therapeutic research--prostatic cancer and models.

PMID- 11950173
TI  - Pulmonary sequestration with ectopic pancreatic tissue in a Wistar Hannover GALAS
      rat.
AB  - A multicystic mass of the lung was found in a male 11-week-old Wistar Hannover
      GALAS rat. The cystic mass was located in the region of the right caudal lobe and
      had no direct communication with the tracheobranchial tree. Histologically, the
      pulmonary mass was composed of variably sized cysts containing mucinous material,
      cellular debris, erythrocytes, and inflammatory cells. In the septal stroma
      between the cysts, well-developed elastic and muscular arteries were present and
      in some areas, ectopic pancreatic tissue was observed. In the rest of the lung
      lobes, there was no evidence of previous pneumonic events or other respiratory
      diseases. Based on these findings, the present case was diagnosed as a congenital
      pulmonary sequestration with ectopic pancreatic tissue.

PMID- 11950174
TI  - Response to "Alternative models for carcinogenicity testing: weight of evidence
      across models" Sam Cohen, Toxicologic Pathology (2001) 29(suppl.): 183-190.

PMID- 11950175
TI  - The value of symphysiotomy.

PMID- 11950176
TI  - Herbal medicinal products during pregnancy: are they safe?

PMID- 11950177
TI  - Minimally invasive surgery for obstructed labour: a review of symphysiotomy
      during the twentieth century (including 5000 cases).
AB  - OBJECTIVE: To compile and make available essential data on symphysiotomy for
      evaluation in the struggle against maternal and fetal mortality and morbidity
      from obstructed labour, which causes the death of 50,000 women each year in low
      resourced countries. DESIGN: Retrospective review of literature. SAMPLE: Five
      thousand symphysiotomies and 1200 caesarean sections from 28 countries on four
      continents. METHODS: The review is based on original papers published 1900 to
      1999, stepwise traced through reference lists. Inclusion criteria were: firstly,
      that the cases reported be consecutive, secondly the presence of an acceptable
      description of methodology and thirdly, the study size was set at a minimum of 25
      cases for analysis of maternal and fetal mortality. Papers comprising only five
      to 24 cases were included in other analyses. All studies were retrospective,
      except the follow up studies. MAIN OUTCOME MEASURES: Maternal and fetal
      mortality; causes of maternal death; fetal mortality in previous deliveries; mode
      of delivery in subsequent pregnancies; symphyseal width after symphysiotomy;
      immediate, short and long term complications; maternal and fetal mortality
      comparing symphysiotomy and caesarean section. RESULTS: Symphysiotomy has been
      extensively studied, modified and refined over the last century, and the
      scientific documentation is substantial. The results indicate that symphysiotomy
      is safe for the mother from a vital perspective, confers a permanent enlargement
      of the pelvis and facilitates vaginal delivery in future pregnancies, and is a
      life saving operation for the child. Severe complications are rare. Symphysiotomy
      compares favourably with caesarean section in terms of risk for the mother's
      life. CONCLUSION: If valid conclusions can be drawn from one hundred years of
      retrospective studies, there is considerable evidence to support a reinstatement
      of symphysiotomy in the obstetric arsenal, for the benefit of women in obstructed
      labour and their offspring.

PMID- 11950178
TI  - Grandmultiparae in a modern setting.
AB  - OBJECTIVE: To compare the incidence of antenatal and intrapartum complications
      and neonatal outcomes among women who had previously delivered five or more times
      (grandmultiparous) with that of age-matched control women who had previously
      delivered two or three times (multiparous). DESIGN: A matched cohort study.
      SETTING: An inner city university maternity hospital in the United Kingdom.
      SAMPLE: Three hundred and ninety-seven grandmultiparous women were compared with
      three hundred and ninety-seven age-matched multiparous women. METHODS: Data on
      the subjects were obtained from a computerised maternity information system
      (SMMIS). Characteristics and complications occurring in the two groups were
      compared. Data validation was performed with a 10% randomised sample of the
      casenotes in both groups. Nineteen relevant data fields were abstracted and
      compared with the matched SMMIS record. Results The overall incidence of
      intrapartum complications for grandmultiparous women was 16% compared with 18% in
      the control multiparous women (odds ratio 0.9, 95% CI 0.6-1.3). Grand multiparity
      was associated with a significantly higher body mass index at booking (P < 0.01)
      and the last antenatal clinic (P < 0.05), an increased incidence of antenatal
      anaemia (22% vs 16%, odds ratio 1.8, 95% CI 1.2-2.8) and a decreased incidence of
      elective caesarean section (6% vs 11%, odds ratio 0.5, 95% CI 0.3-0.9). Agreement
      was greater than 95% in all the data fields reviewed except three. In the 14
      categorical variables reviewed the Cohen's kappa results were in excess of 0.6.
      CONCLUSION: This study suggests that in a developed country with satisfactory
      health care conditions, grandmultiparity should not be considered dangerous,and
      risk assessment should be based on past and present history and not simply on the
      basis of parity.

PMID- 11950179
TI  - Does a traumatic birth experience have an impact on future reproduction?
AB  - OBJECTIVE: To investigate whether women's experiences of their first birth
      affects future reproduction. DESIGN: Prospective cohort study. SETTING: South
      Hospital, Stockholm, Sweden. POPULATION: Six hundred and seventeen women who gave
      birth to their first child 1989-1992. METHODS: A global measure of women's
      experiences of their first birth, assessed two months postpartum, was available
      from a birth centre trial, together with information on a range of background
      variables. This information was linked to the Swedish Medical Birth Register,
      which included information on the number of subsequent births during the
      following 8-10 years. MAIN OUTCOME MEASURES: Number of births (0 or > or =1)
      following the first birth. RESULTS: Women with a negative experience of their
      first birth had fewer subsequent children and a longer interval to the second
      baby (RR 1.7, 95% CI 1.3-2.3). Being 35 years and older (RR 2.6, 95% CI 1.6-3.7),
      or single (RR 2.6, 95% CI 1.7-3.9) was also associated with subsequent
      infertility. CONCLUSION: A negative birth experience was associated with
      subsequent infertility, and women's experiences should therefore be considered
      seriously in the provision of maternity care.

PMID- 11950180
TI  - Reproductive risk factors, pregnancy characteristics and obstetric outcome in
      female doctors.
AB  - OBJECTIVES: To compare maternal risk factors, pregnancy characteristics and
      outcome in female doctors, teachers, and the general obstetric population.
      DESIGN: We analysed obstetric outcomes among 331 female doctors and 656 teachers
      with singleton pregnancies who gave birth at Kuopio University Hospital from
      March 1989 to December 2000. The general obstetric population (n = 21,997) was
      selected as the reference group and logistic regression analysis was used to
      assess pregnancy outcomes in each group separately. RESULTS: Reproductive risk
      factors among female doctors and teachers were similar to those in the general
      obstetric population with the exception of advanced maternal age, number of
      previous terminations, marital status, maternal smoking, obesity, infertility
      treatment and pre-eclampsia. Interestingly, the number of operative deliveries
      did not vary between the groups. Pregnancy outcome among doctors and teachers was
      comparable with that in the general population. CONCLUSIONS: Although doctors and
      teachers appear to represent a group of health-conscious women, obstetricians do
      not vary their management of pregnant doctors and teachers during pregnancy and
      labour.

PMID- 11950181
TI  - Clinical, provider and sociodemographic predictors of late initiation of
      antenatal care in England and Wales.
AB  - OBJECTIVE: To identify factors that are predictive of late initiation of
      antenatal care in England and Wales. DESIGN: A multivariate binomial regression
      model was constructed to examine the association between clinical, provider and
      sociodemographic characteristics and late initiation of antenatal care. SETTING:
      Nine maternity units in Northern England and North Wales. POPULATION: A total of
      20,771 women with a singleton pregnancy who delivered a liveborn or stillborn
      baby between 1 August 1994 and 31 July 1995. All analyses were based on the
      17,765 (85.5%) women for whom information on gestational age at initial
      presentation for antenatal care and other variables incorporated into the
      regression model was retrievable from the case records. RESULTS: Primiparous
      women of high obstetric risk were 13.4% more likely to initiate antenatal care
      after 10 weeks of gestation than a low risk reference group (adjusted OR 1.134,
      95% CI 1.011, 1.272; P = 0.0312), and 34.3% more likely to initiate antenatal
      care after 18 weeks of gestation (adjusted OR 1.343, 95% CI 1.046, 1.724; P =
      0.0208). This association between high obstetric risk status and late initiation
      of antenatal care was not replicated among multiparous women. When the effects of
      other independent variables on gestational age at booking were examined, the
      following characteristics were associated with failure to initiate antenatal care
      by 10 weeks of gestation (P < or = 0.05): maternal age at booking, smoking
      status, ethnicity, type of hospital at booking, the planned pattern of antenatal
      care and the planned place of delivery. Adopting a criterion of 18 weeks of
      gestation exacerbated the association between clinical and sociodemographic
      characteristics and late initiation of antenatal care, but appeared to dilute the
      association between provider characteristics and late initiation of antenatal
      care. CONCLUSIONS: There is a pressing need for further research to identify the
      specific concerns of late bookers, to identify areas where new interventions
      might encourage the uptake of services and to gauge the likely impact of
      increased dissemination of information about the availability of antenatal care
      services.

PMID- 11950182
TI  - Fetal bradycardia due to intrathecal opioids for labour analgesia: a systematic
      review.
AB  - OBJECTIVE: To evaluate fetal and maternal adverse effects of intrathecal opioid
      analgesia during labour. DATA SOURCES: A systematic search was performed, in
      Medline, Embase, the Cochrane Library, bibliographies, and personal contact with
      authors, in any language, up to February 2001. STUDY: selection Full reports on
      randomised comparisons of any analgesia with intrathecal opioid (experimental
      group) with any non-intrathecal opioid regimen (control group) during labour.
      DATA EXTRACTION: Dichotomous data from 24 trials (3513 women). RESULTS: With
      intrathecal opioids, there was a significant increase in the risk of fetal
      bradycardia: odds ratio 1.8 (95% confidence interval 1.0 to 3.1), number-needed
      to-harm 28. The risk of caesarean section due to fetal heart rate abnormalities
      was similar (6.0% versus 7.8%). The incidence of pruritus was significantly
      higher with intrathecal opioids: relative risk 29.6 (95% CI 13.6 to 64.6), number
      needed-to-harm 1.7. CONCLUSIONS: Intrathecal opioids for labour increase the risk
      of fetal bradycardia and maternal pruritus. The risk of subsequent caesarean
      section is not increased.

PMID- 11950183
TI  - Obstetric cholestasis, outcome with active management: a series of 70 cases.
AB  - OBJECTIVE: To determine the nature and outcome of obstetric cholestasis in a
      United Kingdom population. DESIGN: Prospective analysis of clinical outcome in
      women diagnosed with obstetric cholestasis that is actively managed. SETTING:
      Antenatal population of three London hospitals between August 1999 and April
      2001. POPULATION: Seventy women with obstetric cholestasis defined as abnormal
      liver function (one or more abnormality in gamma-glutamyl transpeptidase, alanine
      amino-transferase, aspartate amino-transferase and total bile acids) in a
      pregnant woman with pruritus, in the absence of other pathology. METHODS: All
      women were interviewed weekly regarding their symptoms. All were actively managed
      according to a standardised protocol, which included early delivery before 38
      weeks. Obstetric outcome was recorded. RESULTS: Seventy women of mean age 30 (6)
      years delivered 73 infants. The median gestation at onset of pruritus was 30
      (range 4-39) weeks and at diagnosis of obstetric cholestasis was 33.7 (range 21
      40.7) weeks. Asian women were more likely to be diagnosed with obstetric
      cholestasis. Pruritus was usually severe and generalised, and commonly worst on
      the palms and/or soles of the feet. There were no stillbirths or perinatal
      deaths. Twenty-five women required caesarean section (36%); only four (16%) were
      for fetal distress. Twelve women (17%) delivered before 37 weeks, of which eight
      (67%) were iatrogenic. Ten (14%) infants required admission to the special care
      baby unit of which four (40%) were ventilated. CONCLUSIONS: Policies of active
      management result in increased intervention and associated complications. This
      must be balanced against possible reductions in perinatal mortality.

PMID- 11950184
TI  - Effect of inhibiting the sarcoplasmic reticulum on spontaneous and oxytocin
      induced contractions of human myometrium.
AB  - OBJECTIVE: 1. To assess the contribution of the sarcoplasmic reticulum calcium
      store in the generation of uterine smooth muscle contractions; 2. to evaluate the
      contribution of calcium induced calcium release or ryanodine gated calcium
      channels to myometrial force production. DESIGN: Laboratory scientific study.
      METHODS: Myometrial strips were obtained from women undergoing elective prelabour
      caesarean section at term. These were loaded with the calcium sensitive indicator
      Indo-1 allowing simultaneous assessment of intracellular calcium concentrations
      and force production. The effect of exposing the strips to ryanodine (which
      abolishes calcium induced calcium release), caffeine (which activates calcium
      induced calcium release) and cyclopiazonic acid (which abolishes the sarcoplasmic
      reticulum calcium store) was examined. RESULTS: Exposure to ryanodine had no
      appreciable effect on either the amplitude or the duration of the myometrial
      calcium and force transients but did increase the frequency of contractions
      (139+/-5%). Caffeine did not potentiate force. Cyclopiazonic acid increased
      frequency, duration and amplitude of both calcium and force transients. The
      ability of oxytocin to provoke calcium and force transients in the absence of
      extracellular calcium was abolished by cyclopiazonic acid but not by ryanodine.
      CONCLUSIONS: These results demonstrate that calcium induced calcium release does
      not play a significant role in human myometrium and that no functioning role for
      the ryanodine receptors in human myometrial tissue could be shown. These data
      suggest that the sarcoplasmic reticulum may act to limit contractions and act as
      a calcium sink, rather than to amplify contractions.

PMID- 11950185
TI  - Levels of C-reactive protein in pregnant women who subsequently develop pre
      eclampsia.
AB  - OBJECTIVE: To investigate whether a maternal inflammatory response precedes the
      development of preeclampsia. DESIGN: Cross-sectional study. SETTING: Antenatal
      clinic in an inner city teaching hospital. POPULATION: Two groups of women were
      examined at 23-25 weeks of gestation. The first group (45 women) had normal
      uterine artery Doppler waveforms and subsequently had a normal pregnancy outcome.
      The second group (45 women) had Doppler evidence of impaired placental perfusion
      and 21 (47%) of them had normal outcome, 14 (31%) developed intrauterine growth
      restriction and 10 (22%) developed pre-eclampsia, with or without intrauterine
      growth restriction. METHODS: C-reactive protein, an acute-phase reactant, was
      measured in maternal serum using a highly sensitive method with a detection limit
      of 0.05 mg/L. MAIN OUTCOME MEASURES: Development of pre-eclampsia, as defined by
      the International Society for the Study of Hypertension in Pregnancy.
      Intrauterine growth restriction was defined as birthweight <5th centile for
      gestation and sex of the neonate. RESULTS: The serum C-reactive protein
      concentration in women who subsequently developed pre-eclampsia (median 1.56,
      range 0.55-3.12 mg/L) or delivered a baby with birthweight <5th centile (median
      0.74, range 0.64-1.58 mg/L) was not significantly different from that in women
      with uncomplicated pregnancies (median 1.28, range 0.75-2.08 mg/L; P = 0.95 and P
      = 0.62, respectively). CONCLUSION: These findings suggest that the onset of
      clinical signs of pre-eclampsia may not be preceded by a maternal inflammatory
      response, as assessed by measurement of C-reactive protein.

PMID- 11950186
TI  - The VALUE national hysterectomy study: description of the patients and their
      surgery.
AB  - OBJECTIVES: To describe hysterectomies practised in 1994 and 1995: the patients,
      their surgery and short term outcomes. DESIGN: One of two large cohorts, with
      prospective follow up, recruited to compare the outcomes of endometrial
      destruction with those of hysterectomy. SETTING: England, Wales and Northern
      Ireland. POPULATION: All women who had hysterectomies for non-malignant
      indications carried out during a 12-month period. METHODS: Gynaecologists in NHS
      and independent hospitals were asked to report cases. Follow up data were
      obtained at outpatient follow up approximately six weeks post-surgery. MAIN
      OUTCOME MEASURES: Indication for surgery, method of hysterectomy, ovarian status
      post-surgery, surgical complications. RESULTS: 37,298 cases were reported which
      is estimated to reflect about 45% of hysterectomies performed during the period
      studied. The median age was 45 years, and the most common indication for surgery
      was dysfunctional uterine bleeding (46%). Most hysterectomies were carried out by
      consultants (55%). The proportions of women having abdominal, vaginal or
      laparoscopically-assisted hysterectomy were 67%, 30% and 3%, respectively. Forty
      three percent of women had no ovaries conserved after surgery. The median length
      of stay was five days. The overall operative complication rate was 3.5%, and
      highest for the laparoscopic techniques. The overall post-operative complication
      rate was 9%. One percent of these was regarded as severe, with the highest rate
      for severe in the laparoscopic group (2%). There were no operative deaths; 14
      deaths were reported within the six-week post-operative period: a crude mortality
      rate soon after surgery of 0.38 per thousand (95% CI 0.25-0.64). CONCLUSIONS:
      This large study describes women who undergo hysterectomy in the UK, and presents
      results on early complications associated with the surgery. Operative
      complications occurred in one in 30 women, and post-operative complications in at
      least one in 10. Laparoscopic techniques tend to be associated with higher
      complication rates than other methods.

PMID- 11950187
TI  - Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer:
      a systematic quantitative review.
AB  - OBJECTIVE: To determine the accuracy of outpatient endometrial biopsy in
      diagnosing endometrial cancer in women with abnormal uterine bleeding. DESIGN: A
      systematic quantitative review of published research. METHODS: Studies were
      selected if accuracy of outpatient endometrial biopsy was estimated compared with
      a reference standard. Diagnostic accuracy was determined by pooled likelihood
      ratios for positive and negative test results. There were 1013 subjects in 13
      diagnostic evaluations reported in 11 primary studies. RESULTS: A positive test
      result on outpatient biopsy diagnosed endometrial cancer with a pooled likelihood
      ratio of 66.48 (95% CI 30.04-147.13) while a negative test result had a pooled
      likelihood ratio of 0.14 (95% CI 0.08-0.27). The post test probability of
      endometrial cancer was 81.7% (95% CI 59.7%-92.9%) for a positive test and 0.9%
      (95% CI 0.4%-2.4%) for a negative test. CONCLUSION: Outpatient endometrial biopsy
      has a high overall accuracy in diagnosing endometrial cancer when an adequate
      specimen is obtained. A positive test result is more accurate for ruling in
      disease than a negative test result is for ruling it out. Therefore, in cases of
      abnormal uterine bleeding where symptoms persist despite negative biopsy, further
      evaluation will be warranted.

PMID- 11950188
TI  - A comparison of urethral pressure profilometry using microtip and double-lumen
      perfusion catheters in women with genuine stress incontinence.
AB  - OBJECTIVE: To compare urethral pressure profilometry measurements using microtip
      transducer and double-lumen perfusion catheters. DESIGN: Prospective study.
      SETTING: Tertiary referral urogynaecology unit. SAMPLE: Three hundred and ninety
      two non-pregnant women with various lower urinary tract symptoms. METHODS:
      Multichannel urodynamic investigations were performed using double-lumen
      perfusion catheters with external pressure transducers in 392 women. For those
      301 (76.8%) diagnosed as having genuine stress incontinence, an investigation
      with microtip transducers followed. For data analysis, a mixed-effects model was
      used to evaluate changes in the urethral profilometry and an approach proposed by
      Bland and Altman was applied to access agreement between the two techniques.
      RESULTS: Of the 301 women with genuine stress incontinence, 272 were eligible for
      this study. In resting status, the differences between the two techniques were
      statistically significant (48.9cm H2O vs 73.4cm H2O, P = 0.0001) after adjusting
      for age. Moreover, the agreement study also confirmed that these two techniques
      do not agree sufficiently. CONCLUSION: Maximum urethral closure pressure obtained
      from the double-lumen catheter was significantly higher than that obtained from
      the microtip catheter. Use of the double-lumen catheter for the measurement of
      maximum urethral closure pressure can be considered a reliable technique since
      its reproducibility is as good as that of the microtip catheter. Therefore, the
      diagnosis of 'low pressure urethra' will be different between the two techniques.

PMID- 11950189
TI  - Long term follow up of the cruciate fascial sling for women with genuine stress
      incontinence.
AB  - OBJECTIVE: To determine the long term success of the cruciate fascial sling
      procedure for the treatment of genuine stress incontinence in women. DESIGN: In
      1998, a pre-validated questionnaire was sent to all women who had a cruciate
      fascial sling between 1979 and 1996 under the care of the senior author at a
      District General Hospital and in private practice. PARTICIPANTS: Questionnaires
      were sent to 246 women; 198 (80%) were returned. RESULTS: Overall, 142 women felt
      that they were much improved or cured. The success rate was 74% (95% CI 70%-81%)
      in women having the sling as a primary procedure and 67% (95% CI 54%-81%) in
      women having the sling as a secondary procedure. There was no relationship
      between symptom severity score and age at time surgery, duration of follow up,
      current weight or body mass index, previous surgery for stress incontinence or
      concomitant surgery. Of the 103 women with six or more years of follow up, 29
      felt that their operation had failed, 16 of whom thought that it lasted between
      five and 10 years. Urgency was experienced by 29% of women, three needed to
      perform intermittent self-catheterisation, and 9% found it difficult to empty
      their bladder. Thirty-seven women (19%) experienced problems that they attributed
      to the abdominal wound. CONCLUSION: Although inevitably there are some failures
      over time, the cruciate fascial sling has good long term success rates. Direct
      comparison with the literature is impossible, as few studies have relied on
      properly validated questionnaires.

PMID- 11950191
TI  - Can the levonorgestrel intrauterine system replace surgical treatment for the
      management of menorrhagia?
AB  - Menorrhagia is a common gynaecological condition for which medical treatment is
      often ineffective and a large number of women undergo major surgery. Previous
      short term studies have shown a significant number of women with menstrual
      problems may avoid surgery if a levonorgestrel intrauterine system (LNG-IUS) is
      fitted but no long term studies exist to ascertain if this benefit is sustained.
      This four to five year long term follow up study showed 50% of women continued to
      use the device and 67.4% avoided surgery. The LNG-IUS is well accepted and
      effective in the management of menorrhagia and has major cost implications to the
      National Health Service.

PMID- 11950190
TI  - The effect of oestradiol on vaginal collagen metabolism in postmenopausal women
      with genuine stress incontinence.
AB  - OBJECTIVE: To determine whether oestrogen replacement will produce an improvement
      in the quantity, or quality, of pelvic collagen in postmenopausal women. DESIGN:
      A prospective double-blind placebo controlled trial of oestrogen therapy.
      SETTING: Southmead Hospital, Bristol, UK. POPULATION: Fifty-five postmenopausal
      women with a urodynamic diagnosis of genuine urinary stress incontinence.
      METHODS: Randomisation to a six-month, double-blind, placebo-controlled, trial of
      oestradiol valerate 2mg once daily. A 10mg-30mg periurethral biopsy was taken
      from the vaginal epithelium before and after treatment. Tissue was analysed for
      total collagen content, intermolecular cross-links, advanced glycation end
      products, collagen type ratios and matrix metalloproteinase (MMP) activity.
      RESULTS: Forty-nine women completed the trial of whom 26 received oestrogen and
      23 received placebo. When compared with placebo, oestrogen treatment resulted in
      significant decreases in total collagen (P = 0.0054), the mature cross-link HHL
      (P = 0.0009) and the advanced glycation end-product NFC-1 (P = 0.0009). There was
      a significant rise in the immature cross-link HLKNL (P = 0.0191). Oestrogen
      produced a significant increase in MMP-2 expression (Pro MMP-2, P = 0.0017).
      CONCLUSIONS: Six months treatment with oestrogen has profound effects upon pelvic
      collagen metabolism, stimulating collagen degradation via increased proteinase
      activity. While aged collagen is being lost, new collagen is synthesised as
      witnessed by the increase in the immature cross-links and the decrease in both
      mature cross-links and advanced glycation end-products. Collagen loss contradicts
      previous reports; perhaps aged collagen degradation is merely an early response
      to oestrogen stimulation. We have evidence of new collagen synthesis, and it may
      be that a longer treatment interval would show total collagen content increasing.
      Further studies within this field are warranted.

PMID- 11950192
TI  - Inter-assay variation in antiphospholipid antibody testing.
AB  - We evaluated inter-assay variation in anticardiolipin antibody status, comparing
      three centres, and using different assays among 36 women with recurrent
      miscarriage and 26 controls. There was no more agreement between the laboratories
      than would be predicted on the basis of chance for IgM and only fair agreement
      among the laboratories for IgG. None of the tests were significantly more likely
      to be positive in the cases compared with the controls.

PMID- 11950193
TI  - Trial of vaginal delivery following three previous caesarean sections.

PMID- 11950195
TI  - Sacro-iliitis associated with pregnancy: case report and review of the
      literature.

PMID- 11950194
TI  - Ultrasound-guided, intra-abdominal laser to treat acardiac pregnancies.

PMID- 11950197
TI  - OzFoodNet: enhancing foodborne disease surveillance across Australia: quarterly
      report, July to September 2001.

PMID- 11950196
TI  - Outcomes from the first two years of the Australian hepatitis C surveillance
      strategy.
AB  - The objectives of national hepatitis C surveillance are to identify those at risk
      in order to appropriately target prevention and care programs, and to evaluate
      the impact of these approaches. In 1998 the Communicable Diseases Network
      Australia New Zealand (CDNANZ) appointed the Hepatitis C Surveillance Committee
      to develop and implement approaches for improved hepatitis C surveillance in
      Australia. The Australian Hepatitis C Surveillance Strategy was endorsed in 1999
      and provides a framework for improvements to national hepatitis C surveillance.
      The strategy covers two main surveillance activities: surveillance of incident
      and prevalent hepatitis C, and the long-term outcomes of hepatitis C. The
      committee (now the CDNA Viral Hepatitis Surveillance Committee) has continued to
      facilitate the implementation of the recommendations proposed. Progress towards
      improvement of hepatitis C surveillance in Australia includes the development of
      standard case reporting for hepatitis C, collation of data on incident and
      prevalent hepatitis C from a range of populations at lower and higher risk of
      hepatitis C, and collation of data from liver transplant registries. Advances in
      the implementation of the strategy are incremental. While there is enthusiastic
      commitment towards improving hepatitis C surveillance in Australia, the number of
      cases, the capacity and competing priorities of State and Territory health
      departments has meant that implementation has been challenging, highlighting the
      difficulties in introducing new systems into an already complex situation.

PMID- 11950198
TI  - Australia's Imported Food Program--a valuable source of information on micro
      organisms in foods.
AB  - Foods imported into Australia are subject to laboratory testing for
      microbiological and chemical hazards under the Imported Food Program (IFP) for
      the purposes of protecting public health and safety. The program, operating under
      the Imported Food Control Act 1992, is jointly administered by the Australian
      Quarantine Inspection Service (AQIS) and the Australia New Zealand Food Authority
      (ANZFA). Foods that fail under the IFP are subsequently subjected to appropriate
      treatment to rectify the problem, or are destroyed or re-exported. This article
      presents a limited analysis of IFP test results on selected foods imported
      between 1995 and 1999. As corrective action is taken immediately on the basis of
      failing test results, regular analysis of collated data is not considered a
      priority. Nonetheless these data potentially represent an important source of
      information on the nature of food microorganisms detected in imported foods. For
      example, IFP data could be used to focus local and state-based food surveillance
      efforts, provide information to importers, to inform national initiatives such as
      OzFoodNet, and to better target investigative and preventative efforts concerning
      foodborne illness.

PMID- 11950199
TI  - An outbreak of Salmonella typhimurium PTI35 gastroenteritis associated with a
      minimally cooked dessert containing raw eggs.
AB  - In April 2000, we investigated an outbreak of gastroenteritis amongst attendees
      of a local community dinner in a Perth suburb. Of the 98 people interviewed
      (response rate 98%), 53 reported gastrointestinal symptoms (attack rate 54%).
      Faecal cultures from 11 cases, 2 food preparers, 1 waitress and leftover mock ice
      cream dessert grew Salmonella Typhimurium PT135. Of the 3 food handlers, one was
      asymptomatic, another gave an unclear history of onset of illness and the
      waitress claimed illness onset 9 days after the dinner. A cohort study implicated
      fruit salad (RR 1.64 [95% CI: 1.05-2.58], p=0.017) and/or mock ice-cream dessert
      (RR 1.78 [95% CI: 0.91-3.52], p=0.045). Eggs used to make the mock ice-cream
      dessert were supplied directly from the producer who used inappropriate shell
      cleaning methods. The method of preparation of the dessert encouraged
      contamination. Salmonella species were not isolated in poultry faecal samples
      collected from the implicated egg farm. The cause of this outbreak was almost
      certainly the ice-cream dessert with contamination most likely resulting either
      from the eggs used to make the dessert or one or both of the food preparers,
      coupled with inadequate cooking of the dessert. Eggs used in preparing food for
      mass consumption should be sourced from distributors with approved cleaning
      procedures. Furthermore, pasteurised egg products or egg pulp should be used in
      the preparation of uncooked or minimally cooked dishes.

PMID- 11950200
TI  - An outbreak of Salmonella typhimurium phage type 135 infection linked to the
      consumption of raw shell eggs in an aged care facility.

PMID- 11950201
TI  - Reappearance of human cases due to Murray Valley encephalitis virus and Kunjin
      virus in central Australia after an absence of 26 years.
AB  - Murray Valley encephalitis (MVE) and Kunjin virus disease are endemic in the
      tropical parts of the Northern Territory and Western Australia, but have been
      absent from Central Australia since 1974. In 2000, 5 laboratory-confirmed cases
      of encephalitis occurred over a short period in the normally dry inland region of
      Central Australia. The sudden occurrence of cases in March and April 2000
      followed unusually high rainfall in the preceding months and evidence of
      flavivirus activity in the endemic areas in the Kimberley region of Western
      Australia. Further cases were reported in the following wet season, without
      preceding human cases in known endemic areas. These findings indicate the
      reintroduction of these viruses into Central Australia and establishment of local
      cycles of infection with an ongoing risk to the local population. This area may
      also act as a potential source for reintroduction of MVE into south-eastern
      Australia.

PMID- 11950202
TI  - Epidemiology of invasive meningococcal disease in north Queensland, 1995 to 1999.
AB  - This study describes all episodes of invasive meningococcal disease (n=120)
      acquired in north Queensland over the 5 year period 1995 to 1999. Indigenous
      people had a 3-fold greater risk than others of acquiring invasive meningococcal
      disease. There were 7 deaths, six in non-indigenous people. The majority (72.4%)
      of identified isolates were serogroup B. We found no evidence of significant
      resistance to the antibiotics recommended for treatment or chemoprophylaxis. Two
      outbreaks of disease were identified, one serogroup B and one serogroup C.
      Compared to the previous 5 years (1990 to 1994) there were far fewer cases of
      serogroup C disease and a lower incidence and risk of invasive meningococcal
      disease among indigenous people.

PMID- 11950203
TI  - Editorial: towards improving influenza surveillance in Australia.

PMID- 11950204
TI  - Rising prevalence of genital Chlamydia trachomatis infection in heterosexual
      patients at the Sydney Sexual Health Centre, 1994 to 2000.
AB  - This study sought to investigate trends in the prevalence of genital Chlamydia
      trachomatis infection in heterosexual patients attending an urban sexual health
      service. Data from cases of C. trachomatis in all new self-referred heterosexual
      patients who were tested at the Sydney Sexual Health Centre from 1994 to 2000
      were extracted from the Centre's database. Female sex workers and homosexually
      active men were excluded. Over the study period the prevalence of C. trachomatis
      infection doubled from 1.8 per cent to 3.5 per cent among the women (p=0.004) and
      tripled from 2.1 per cent to 6.6 per cent among the men (p<0.001) who were
      tested. Both men and women reported an increasing overall trend in the mean (but
      not median) number of sexual partners during the previous 3 months (p=0.039 and
      p=0.001, respectively). There were modest increases in the proportion of men and
      women that reported unprotected vaginal or anal sex in the previous 3 months,
      from 76.5 per cent to 81.7 per cent for males (p=0.122) and from 65.1 per cent to
      70.2 per cent (p=0.01) for females. The introduction of more sensitive DNA-based
      testing probably only accounted for 8 per cent of the rise in prevalence among
      women and 16 per cent among men. These findings complement the rising trends in
      national notifications of C. trachomatis infection. Further investigation and
      interventions on a national scale to reduce the prevalence of C. trachomatis seem
      timely.

PMID- 11950206
TI  - Surveillance systems reported in CDI, 2002.

PMID- 11950205
TI  - Public Health Laboratory Network (PHLN).

PMID- 11950207
TI  - Composition of Australian influenza vaccine for the 2002 season.

PMID- 11950208
TI  - Communicable Diseases Surveillance: highlights for 4th quarter, 2001.

PMID- 11950209
TI  - Fragmentation of influenza surveillance in Australia.
AB  - Monitoring of community influenza through sentinel practice networks is essential
      to track the onset and progress of epidemics. In 1999, the Influenza Pandemic
      Planning Committee of the Communicable Diseases Network Australia New Zealand
      (CDNANZ) recommended that a national surveillance system be established
      comprising both community-based and institutional surveillance. In 2001, however,
      influenza surveillance remains fragmented in Australia and mainly restricted to
      major cities. Methods of surveillance and reporting of influenza activity vary
      between States and even within States. Three disparate case definitions are in
      use for reporting influenza-like illnesses. Many sentinel sites do not have
      laboratory support for confirmation of influenza or identification of circulating
      strains. Dissemination of information is uncoordinated and without a standardised
      reporting format for collation at a national level. Prompt attention to these
      issues is important to ensure an adequate public health response to future
      influenza virus epidemics or a pandemic.

PMID- 11950210
TI  - Copper-psychoactive drug complexes: a voltammetric approach to complexation by
      1,4-benzodiazepines.
AB  - Copper complexation by the 1,4-benzodiazepines medazepam, diazepam, flurazepam,
      nitrazepam, and clonazepam was investigated using differential pulse polarography
      and cyclic voltammetry at a mercury electrode in 0.10 M KNO3 and pH 7.0 +/- 0.1.
      Because the 1,4-benzodiazepines are easily reduced at a mercury electrode through
      the two-electron reduction of the 4,5-azomethine functional group, copper
      reduction, as well as that of the ligands, was analyzed under varying
      experimental conditions. In most situations adsorption phenomena occurred and
      their influence on voltammetric signals had to be carefully analyzed. The
      voltammetric behavior was then interpreted in terms of complex formation. The
      results showed that all benzodiazepines can act as ligands toward copper(II)
      ions, forming 1:1 and 1:2 complexes with similar stabilities. The stoichiometric
      acidity constants of the benzodiazepines under study were also determined by
      potentiometric titration in water-ethanol medium and 0.10 M KNO3 and then
      extrapolated to 0% concentration of ethanol.

PMID- 11950211
TI  - Spectrophotometric assays for L-lysine alpha-oxidase and gamma-glutamylamine
      cyclotransferase.
AB  - A new assay for l-lysine alpha-oxidase is described. In this assay, the oxidized
      product generated from l-lysine is reacted with semicarbazide to form alpha-keto
      epsilon-aminocaproate semicarbazone. Formation of the alpha-keto acid
      semicarbazone is continuously monitored spectrophotometrically at 248 nm (epsilon
      10,160 +/- 240 M(-1) cm(-1)). The method was adapted to provide a new assay for
      gamma-glutamylamine cyclotransferase. This enzyme catalyzes the conversion of
      many l-gamma-glutamylamines to 5-oxo-l-proline and free amine. A biologically
      important substrate is N(epsilon)-(gamma-l-glutamyl)-l-lysine, which is converted
      to 5-oxo-l-proline and l-lysine by the action of gamma-glutamylamine
      cyclotransferase. The l-lysine generated from N(epsilon)-(gamma-l-glutamyl)-l
      lysine in an endpoint assay is converted to alpha-keto epsilon-aminocaproate
      semicarbazone in the presence of semicarbazide, excess l-lysine alpha-oxidase,
      and catalase. The methods were applied to the determination of gamma
      glutamylamine cyclotransferase activity of partially purified preparations of the
      bovine kidney enzyme and to detect gamma-glutamylamine cyclotransferase activity
      in rat kidney and liver homogenates.

PMID- 11950212
TI  - Determination of arginine, asymmetric dimethylarginine, and symmetric
      dimethylarginine in human plasma and other biological samples by high-performance
      liquid chromatography.
AB  - Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide
      synthase (NOS), may be related to reduced biosynthesis of nitric oxide in
      diseases associated with accelerated atherosclerosis. The closely related
      compound symmetric dimethylarginine (SDMA) does not inhibit NOS, but may compete
      with arginine for cellular uptake, thereby limiting substrate availability for
      NOS. We report on a method for the simultaneous measurement of arginine, ADMA,
      and SDMA as a tool to gain insight in the role of these compounds in the
      regulation of NOS activity. Sample cleanup was performed by solid-phase
      extraction on polymeric cation-exchange columns using monomethylarginine as
      internal standard. After derivatization with ortho-phthaldialdehyde reagent
      containing 3-mercaptopropionic acid, analytes were separated by isocratic
      reversed-phase HPLC with fluorescence detection. The stable derivatives were
      separated with near baseline resolution. Using a sample volume of 0.2 ml, linear
      calibration curves were obtained with limits of quantification of 0.08 microM for
      arginine and 0.01 microM for ADMA and SDMA. Analytical recovery was 98-102%, and
      interassay CV was better than 3%. Plasma from healthy volunteers (n = 53)
      contained 94 +/- 26 microM arginine, 0.42 +/- 0.06 microM ADMA, and 0.47 +/- 0.08
      microM SDMA. Due to its high precision and sensitivity this method is a valuable
      tool in research on the metabolism of dimethylated arginines and their role in
      the regulation of NOS activity.

PMID- 11950213
TI  - A novel fluorescence competitive assay for glucose determinations by using a
      thermostable glucokinase from the thermophilic microorganism Bacillus
      stearothermophilus.
AB  - We describe the use of a thermostable glucokinase in a novel competitive
      fluorescence assay for glucose. Glucokinase from Bacillus stearothermophilus
      (BSGK) was found to retain enzymatic activity in solution for over 20 days. The
      single cysteine residue in BSGK, which is near the active site, was labeled with
      a fluorescent probe, 2-(4-iodoacetamidoanilino)naphthalene-6-sulfonic acid. The
      ANS-labeled BSGK displayed a modest 25% decrease in the emission intensity upon
      binding glucose but no change in lifetime. To obtain a larger spectral change we
      developed a competitive assay for glucose using the intrinsic tryptophan
      fluorescence from BSGK and a resonance energy transfer (RET) acceptor-labeled
      sugar. The sugar-labeled acceptor quenched the BSGK tryptophan emission, and the
      quenching was reversed upon addition of glucose. The use of RET as the sensing
      mechanism can be easily extended to longer wavelengths for a more practical
      glucose sensor.

PMID- 11950214
TI  - Kinetics of influenza hemagglutinin-mediated membrane fusion as a function of
      technique.
AB  - Reliable techniques are required to evaluate the plausibility of proposed
      membrane fusion mechanisms. Here we have studied the kinetics of establishing the
      lipidic connection between hemagglutinin-expressing cells (HA-cells) and red
      blood cells (RBC) labeled with octadecylrhodamine, R18, using three different
      experimental approaches: (1) the most common approach of monitoring the rate of
      the R18 dequenching in a cuvette with a suspension of RBC/HA-cell complexes; (2)
      video fluorescence microscopy (VFM) to detect the waiting times before the onset
      of R18 redistribution, not dequenching, for each RBC attached to an adherent HA
      cell; and (3) a new approach based on blockage of RBC fusion to an adherent HA
      cell at different time points by lysophosphatidylcholine (LPC), so that only the
      cell pairs which, at the time of LPC application, had fused or were irreversibly
      committed to fusion contributed to the final extent of lipid mixing. The LPC
      blockage and VFM gave very similar estimates for the fusion kinetics, with LPC
      monitoring also those sites committed to the lipid mixing process. In contrast,
      R18 dequenching in the cuvette was much slower, i.e., it monitors a much later
      stage of dye redistribution.

PMID- 11950215
TI  - Effects of membrane partitioning and other physical chemical properties on the
      apparent potency of "membrane active" compounds evaluated using red blood cell
      lysis assays.
AB  - The membrane-destabilizing properties of Amphotericin B and Zwittergent were used
      as benchmark compounds for examining in detail their membrane-altering effects in
      a series of human red blood cell lysis assays. The procedures included examining
      dose responses and the effects of different cell concentrations on potency in rbc
      lysis assays. In order to enhance detection of subtle membrane effects, we also
      used a range of NaCl concentrations to osmotically stress the rbc's. Using the
      benchmark compounds, a set of conditions was developed for examination of subtle
      membrane effects that may be applied to series of compounds with suspected
      membrane-perturbation activity. A group of experiments was defined that allow
      detection of the most important membrane-modifying behaviors among a diverse
      group of compounds. From an initial screen of bacterial growth inhibition over
      150 compounds were examined for membrane-altering properties using the limited
      experimental protocols developed from the benchmark compounds. Several dose
      response patterns were observed as useful for classifying compounds based on
      their tendency to alter membrane integrity and to partition into the lipids of
      membranes, as well as their propensity to form aggregates or precipitates. The
      methods may prove generally useful for distinguishing compounds whose primary
      activity is membrane destabilization from more interesting and useful
      pharmacological mechanisms of action.

PMID- 11950216
TI  - Simultaneous quantitative analysis of sphingoid base 1-phosphates in biological
      samples by o-phthalaldehyde precolumn derivatization after dephosphorylation with
      alkaline phosphatase.
AB  - This paper describes a simultaneous analytical method for the measurement of
      sphingoid base 1-phosphates and sphingoid bases from a variety of biological
      samples. This method consists of two steps of sample pretreatment: the enzymatic
      dephosphorylation of sphingoid base 1-phosphates by alkaline phosphatase (APase)
      and the subsequent analysis of o-phthalaldehyde (OPA) derivatives of the
      liberated sphingoid bases by HPLC. By introducing C17-sphingosine 1-phosphate and
      C17-sphingosine as internal standards, not only phytosphingosine 1-phosphate,
      sphingosine 1-phosphate, and sphinganine 1-phosphate but also phytosphingosine,
      sphingosine, and sphinganine present in a sample could be quantified in 12 min on
      a C18 reversed-phase column with a simple mobile phase of acetonitrile:deionized
      distilled water (90:10, v/v). With this HPLC method, we could reproducibly
      analyze the levels of sphingoid base 1-phosphates over a broad range of
      concentrations from 0.5 to 100.0 pmol from various biological samples including
      serum, cultured cells, and rat tissue homogenates. The conversion of sphingoid
      base 1-phosphates into sphingoid bases increased the stability of the OPA
      adducts. Thus, this indirect measurement of sphingoid base 1-phosphates increased
      the sensitivity and reproducibility of the method. This HPLC method was also used
      to measure the changes in the levels of sphingoid base 1-phosphates in cultured
      cells after treatment with 1,25-(OH)2D3, a sphingosine kinase activator, or with
      fumonisin B1, a sphinganine N-acyltransferase inhibitor.

PMID- 11950217
TI  - Carbohydrate analysis of bacterial polysaccharides by high-pH anion-exchange
      chromatography and online polarimetric determination of absolute configuration.
AB  - A significant problem in structure determination of complex carbohydrates,
      especially for bacterial polysaccharides, is determination of the absolute
      configuration of the component monosaccharides. A number of analytical methods
      have been used for this purpose but, as a result of the wide variety of chemical
      properties of sugars found in complex polysaccharides, no single method is
      universally applicable. High-resolution gas chromatography of volatile
      derivatives with chiral reagents is the most widely used method. Optical
      activity, although direct and simple, lacks sensitivity generally requiring a
      large quantity of pure monosaccharide. We report a combination of high
      performance anion-exchange chromatography (HPAEC) with combined electrochemical
      pulsed amperometric detection and in-line detection of optical rotation with an
      in-line laser polarimeter for analysis of a number of sugars found in complex
      polysaccharides. We show that application of the method for analysis of capsular
      polysaccharides of several gram-positive and gram-negative pathogenic bacteria
      provides useful information simultaneously on carbohydrate composition and the
      enantiomeric configuration of component sugars.

PMID- 11950218
TI  - Highly sensitive and specific detection of viable Escherichia coli in drinking
      water.
AB  - A highly sensitive and specific assay method was developed for the detection of
      viable Escherichia coli as an indicator organism in water, using nucleic acid
      sequence-based amplification (NASBA) and electrochemiluminescence (ECL) analysis.
      Viable E. coli were identified via a 200-nt-long target sequence from mRNA (clpB)
      coding for a heat shock protein. In the detection assay, a heat shock was applied
      to the cells prior to disruption to induce the synthesis of clpB mRNA and the
      mRNA was extracted, purified, and finally amplified using NASBA. The amplified
      mRNA was quantified with an ECL detection system after hybridization with
      specific DNA probes. Several disruption methods were investigated to maximize
      total RNA extracted from viable cells. Optimization was also carried out
      regarding the design of NASBA primer pairs and detection probes, as well as
      reaction and detection conditions. Finally, the assay was tested regarding
      sensitivity and specificity. Analysis of samples revealed that as few as 40 E.
      coli cells/mL can be detected, with no false positive signals resulting from
      other microorganisms or nonviable E. coli cells. Also, it was shown that a
      quantification of E. coli cells was possible with our assay method.

PMID- 11950219
TI  - Fluorometric microplate assay to measure glutathione S-transferase activity in
      insects and mites using monochlorobimane.
AB  - Elevated levels of glutathione S-transferases (GSTs) play a major role as a
      mechanism of resistance to insecticides and acaricides in resistant pest insects
      and mites, respectively. Such compounds are either detoxicated directly via phase
      I metabolism or detoxicated by phase II metabolism of metabolites as formed by
      microsomal monooxygenases. Here we used monochlorobimane (MCB) as an artificial
      substrate and glutathione to determine total GST activity in equivalents of
      single pest insects and spider mites in a sensitive 96-well plate-based assay
      system by measuring the enzymatic conversion of MCB to its fluorescent bimane
      glutathione adduct. The differentiation by their GST activity between several
      strains of the two-spotted spider mite, Tetranychus urticae (Acari:
      Tetranychidae), with different degrees of resistance to numerous acaricides was
      more sensitive with MCB compared to the commonly used substrate 1-chloro-2,4
      dinitrobenzene (CDNB). Compared to an acaricide-susceptible reference strain, one
      field population of T. urticae showed a more than 10-fold higher GST activity
      measured with MCB, in contrast to a less than 2-fold higher activity when CDNB
      was used. Furthermore, we showed that GST activity can be sensitively assessed
      with MCB in homogenates of pest insects such as Heliothis virescens, Spodoptera
      frugiperda (Lepidoptera: Noctuidae), Plutella xylostella (Lepidoptera:
      Yponomeutidae), and Myzus persicae (Hemiptera: Aphididae).

PMID- 11950220
TI  - Attomole electrophoretic analysis of catecholamines using copper-catalyzed
      intramolecular cyclization.

PMID- 11950221
TI  - A high-throughput system for identifying human interleukin-2 inducers and/or
      repressors based on the expression of a reporter gene in Jurkat T cells.

PMID- 11950222
TI  - Analysis of oligosaccharide structures of glycoproteins in polyacrylamide gel.

PMID- 11950223
TI  - Housekeeping gene variability in normal and carcinomatous colorectal and liver
      tissues: applications in pharmacogenomic gene expression studies.

PMID- 11950224
TI  - A Modified pBluescript-based vector for facile cloning and transcription of RNAs.

PMID- 11950225
TI  - An assay for oxidant regulation of protein tyrosine phosphatase activity.

PMID- 11950226
TI  - The inner wall of Schlemm's canal.

PMID- 11950227
TI  - Age-related changes in vitreous mobility as measured by video B scan ultrasound.
AB  - Many vitreoretinal disorders increase in incidence with age. The vitreous is
      known to liquefy and separate from the retina in aging patients. Liquefaction and
      partial vitreous separation alter the biomechanics of the vitreous and change the
      tractional forces exerted by the vitreous on the retina. These forces may play a
      role in the development of a variety of vitreoretinal pathologies including
      retinal tears, cystoid macular edema, and macular holes. The purpose of this
      study is to test the hypothesis that the biomechanical properties of the vitreous
      change with aging and can be quantified by analysis of kinetic B scan ultrasound
      recordings. Kinetic B scan ultrasound recordings were made of the vitreous gel of
      38 subjects from ages 18 to 91 during standard eye motions. The recordings were
      graded for speckle density (hyperreflective areas on ultrasound) and were
      examined for the presence or absence of posterior vitreous detachment. Tracking
      of the speckles on a polar grid allowed for the calculation of the angle
      travelled by the speckle relative to the angle travelled by the eye. The
      recordings were also analysed for "overshoot time", or the amount of time that
      the speckles continued to travel after the cessation of eye movement. The
      vitreous of subjects of age less than 46 years demonstrated significantly less
      speckle density (P < 0.001), less overshoot time (P < 0.001), and less angle
      travelled by the speckle relative to the angle travelled by the eye when compared
      to older subjects (P = 0.006). The presence or absence of PVD as diagnosed by
      kinetic ultrasound was not a significant predictor for speckle density, overshoot
      time, or ratio of angular motions. The results indicate that aging affects the
      biomechanics of the vitreous in ways which can be quantified with kinetic
      ultrasound analysis using the grading system described above.

PMID- 11950228
TI  - Neuroprotective effects of brimonidine against transient ischemia-induced retinal
      ganglion cell death: a dose response in vivo study.
AB  - The purpose of this study was to investigate the dose-response effects of
      topically administered brimonidine (BMD) on retinal ganglion cell (RGC) survival,
      short and long periods of time after transient retinal ischemia. In adult Sprague
      Dawley rats, RGCs were retrogradely labeled with the fluorescent tracer
      fluorogold (FG) applied to both superior colliculi. Seven days later, the left
      ophthalmic vessels were ligated for 90 min. One hr prior to retinal ischemia, two
      5 microl drops of saline alone or saline containing 0.0001, 0.001, 0.01 or 0.1%
      BMD were instilled on the left eye. Rats were processed 7, 14 or 21 days later
      and densities of surviving RGCs were estimated by counting FG-labeled RGCs in 12
      standard regions of each retina. The following have been found. (1) Seven days
      after 90 min of transient ischemia there is loss of approximately 46% of the RGC
      population. (2) topical pre-treatment with BMD prevents ischemia-induced RGC
      death in a dose-dependent manner. Administration of 0.0001% BMD resulted in the
      loss of approximately 37% of the RGC population and had no significant
      neuroprotective effects. Administration of higher concentrations of BMD (0.001 or
      0.01%) resulted in the survival of 76 or 90%, respectively, of the RGC
      population, and 0.1% BMD fully prevented RGC death in the first 7 days after
      ischemia. (3) Between 7 and 21 days after ischemia there was an additional slow
      cell loss of approximately 25% of the RGC population. Pre-treatment with 0.1% BMD
      also reduced significantly this slow cell death. These results indicate that the
      neuroprotective effects of BMD, when administered topically, are dose-dependent
      and that the 0.1% concentration achieves optimal neuroprotective effects against
      the early loss of RGCs. Furthermore, this concentration is also effective to
      diminish the protracted loss of RGCs that occurs with time after transient
      ischemia.

PMID- 11950229
TI  - Targeted gene transfer to corneal stroma in vivo by electric pulses.
AB  - This study was conducted to develop a method of targeted gene transfer by
      electric pulses to a selected area of corneal stroma in vivo. Plasmid DNA with a
      green fluorescent protein (GFP) gene under a cytomegalovirus promoter was
      injected through the corneal pocket into the corneal stroma of the adult Brown
      Norway rat, and various intensities of electric pulses ranging from 10 to 30 V
      were delivered to the corneal epithelial side with an electric probe. Direct
      stereomicroscopy of the fluorescent using real-time imaging was used to determine
      in vivo gene expression on days 1, 2, 4, 6, 8, 10, 15, and 20 after gene
      transfer. Transgene expression was detected in the corneal stroma as early as day
      1 and until day 15. The most intense expression was noted on days 4 and 6. Gene
      transfer was most effective using eight electric pulses of 20 V for 50 msec.
      Histologic study disclosed GFP expression in keratocytes within the targeted
      area. There was no apparent cell damage in the gene transferred cells. No
      apparent inflammation was found in the anterior chamber or trabecular cells when
      electric pulses less than 30 V were used. In summary, the present technique
      transferred the gene of interest to a highly selected area of corneal stroma with
      no apparent damage. This method will likely be useful not only for developing
      gene therapy for corneal diseases but also for corneal research in general.

PMID- 11950230
TI  - Specific transduction of the leading edge cells of migrating epithelia
      demonstrates that they are replaced during healing.
AB  - As wounds in stratified epithelia close, the numbers of cells at the leading edge
      of migration decreases. It is not known whether cells at the leading edge are
      continually replaced or whether some retain their position at the leading edge
      over time. Replication-deficient adenovirus carrying the green fluorescent
      protein gene was applied to corneal epithelial wounds in mice and it was found
      that they primarily infect the leading edge cells of healing epithelium. Eighteen
      hr after viral transduction, green fluorescent protein expressing cells were
      located in the apical layer at varying distances behind the leading edge. These
      data indicate that leading edge cells are replaced during healing of stratified
      epithelia.

PMID- 11950231
TI  - Inhibition of scleral proteoglycan synthesis blocks deprivation-induced axial
      elongation in chicks.
AB  - A specific inhibitor of proteoglycan synthesis was administered to chicks
      undergoing the development of form deprivation myopia in order to test the
      hypothesis that increases in proteoglycan synthesis are responsible for normal
      and/or deprivation-induced ocular elongation in chicks. Chicks undergoing
      monocular form deprivation were treated with p-nitrophenyl-beta-D-xylopyranoside
      (beta-xyloside) via i.p. injection every 8 hr for 5-11 days. Ocular measurements
      were made at the end of the experiment using high frequency A-scan ultrasound in
      conjunction with a LabView (v. 5.0) analysis program. Following ultrasound
      measurements, sclera were isolated and proteoglycans characterized by Sepharose
      CL-2B and Western blot analyses. Preliminary studies indicated that i.p.
      administration of beta-xyloside maximally inhibited sulfate incorporation into
      proteoglycans 8 hr after administration. Beta-xyloside treatment resulted in a
      significant reduction in the axial length, vitreous chamber depth, and rate of
      axial elongation of form deprived eyes as compared with form deprived eyes from
      vehicle treated chicks (P < 0.01, P < 0.05, P < 0.05, respectively). No
      significant differences were detected in anterior chamber depth, lens thickness,
      choroid thickness or retina thickness in form deprived eyes of beta-xyloside
      treated chicks as compared with that of vehicle controls. No significant
      differences were detected in contralateral non-deprived fellow eyes between beta
      xyloside treated and vehicle treated chicks for any ocular measurement. Analysis
      of proteoglycans indicated that the xyloside treatment resulted in the
      accumulation of smaller proteoglycans due, in part, to the presence of
      underglycosylated aggrecan within the scleral matrix. These results indicate that
      interruption of normal scleral proteoglycan synthesis inhibits form deprivation
      induced ocular elongation, supporting the hypothesis that scleral proteoglycan
      synthesis and accumulation are largely responsible for increases in axial length
      in form deprived chick eyes.

PMID- 11950232
TI  - Studies on singlet oxygen formation and UVA light-mediated photobleaching of the
      yellow chromophores in human lenses.
AB  - The protein-bound chromophores, which increase with aging in the human lens, act
      as UVA sensitizers, producing almost exclusively singlet oxygen in vitro. Direct
      irradiation of whole, aged human lenses with high intensity UVA light (200 mW cm(
      2) for 24 hr), however, failed to produce singlet oxygen damage, as evidenced by
      the lack of either His or Trp photodestruction. Total homogenates of human lenses
      prepared in a cuvette under air did show destruction of His and Trp residues by
      UVA light, but no destruction was seen when equivalent homogenates were prepared
      under argon. These data are consistent with the idea that the low oxygen levels
      in the lens prevent singlet oxygen damage in vivo.UVA irradiation of aged human
      lenses in culture caused an extensive photobleaching of the yellow chromophores.
      A time course indicated that the photobleaching increased with time, with
      significant color loss apparent after 6 hr. Homogenization of the irradiated and
      dark control lenses in 6 M guanidine-HCl, followed by determination of the
      difference spectrum, showed approximately 50% bleaching of compounds with a
      lambda(max) at 355 nm. Similarly, fluorophores with a lambda(max) for excitation
      of 355 nm and for emission of 420 nm were 50% destroyed by the UVA light. Similar
      results were obtained in vitro by the anaerobic irradiation of a sonication
      solubilized WI fraction from type II brunescent cataracts and from aged human
      lenses. In this system, there was an initial bleaching of 15% after 30 min of
      irradiation, followed by a slow increase over the next 6 hr to a final bleaching
      of 30%. The addition of 1.0 m M ascorbic acid, but not 1.0 m M glutathione (GSH),
      increased the photobleaching to 60% under argon, and the loss of ascorbate could
      be detected under these anaerobic conditions. In the presence of air, UVA light
      produced no photobleaching, but rather caused a three-fold increase in absorbance
      at 345 nm, which was prevented by the inclusion of 1.0 m M ascorbic acid and
      almost 50% inhibited by 1.0 m M GSH. The data are consistent with the conversion
      of the triplet state of the sensitizers to anion and cation radicals in the
      absence of oxygen. Photobleaching may occur either by dismutation of the anion
      radical or by reduction of the anion radical by ascorbate via type I chemistry.
      UVA irradiation of an enriched fraction of sensitizers from a proteolytic digest
      from type II cataract lenses produced a 63% bleaching at 330 nm in the absence of
      oxygen, and the almost complete loss of the A(330) absorbing and 350/450 nm
      fluorescent peaks upon HPLC separation. This loss correlated with the loss of the
      ability of the irradiated fraction to produce singlet oxygen in vitro upon
      subsequent UVA irradiation.

PMID- 11950233
TI  - Differential gene expression in the lens epithelial cells from selenite injected
      rats.
AB  - The mechanism causing loss of integrity of lens epithelial cells induced by an
      overdose of sodium selenite remains to be elucidated. The aim of the present
      experiment was to search for changes in gene expression in epithelial cells of
      lenses from rats developing selenite cataract. One day after injection of
      selenite into 12 day old rats, gene expression in lens epithelial cells was
      analysed using a commercial DNA array (Atlas Rat 1.2 Array). Changes were
      confirmed by RT-PCR. Of 1176 genes assayed by hybridization, 91 genes showed
      differences in expression between normal and selenite lenses. The three genes
      showing the greatest changes were: cytochrome c oxidase subunit I (COX-I,
      decrease), gastric inhibitory polypeptide (GIP, decrease), and early growth
      response protein-1 (EGR-1, increase). Both COX-I and EGR-1 have been reported to
      be involved with apoptosis. These results suggest that changes in COX-I and EGR-1
      expression in lens epithelial cells might play important roles in apoptosis and
      altered metabolism leading to selenite cataract.

PMID- 11950234
TI  - Pterygial derived fibroblasts express functionally active histamine and epidermal
      growth factor receptors.
AB  - Pterygia are characterised by a fleshy outgrowth of altered conjunctival tissue
      over the cornea and are most common in tropical regions. Pterygial fibroblasts
      are characteristically distinct from normal conjunctival fibroblasts, and
      therefore the aim of this study was to determine the presence and functional
      significance of histamine and epidermal growth factor (EGF) receptors in these
      cells. Pterygial specimens were cultured in vitro and cellular outgrowths were
      phenotypically characterised as fibroblasts using vimentin and cytokeratin
      staining. Intracellular calcium mobilization was used to characterise the
      functional activity of histamine receptors on these cells. Maximal response was
      obtained with 100 microM histamine. However, lower concentrations of histamine
      also caused mobilization of calcium that were totally abolished by pre-incubation
      with H1 but not H2 or H3 receptor antagonists. EGF receptor was diffusely
      expressed over the cell surfaces. EGF stimulated receptor internalization, ERK
      protein phosphorylation and intracellular calcium mobilization. Therefore,
      fibroblasts derived from human pterygia express functionally active histamine and
      epidermal growth factor receptors. Controlled modification of either the
      receptors or the appropriate ligands could have beneficial effects in pterygia
      treatment.

PMID- 11950235
TI  - Increased expression of p21(WAF-1/CIP-1) in the lens epithelium of rat sugar
      cataract.
AB  - It has been demonstrated that exquisite regulation of the cell cycle between the
      activation and inhibition is crucial to maintain the transparency of the ocular
      lens. While it is generally recognized that the sugar cataract is accompanied by
      the enhanced proliferation of lens epithelial cells (LECs), it is unclear whether
      or not an inhibitory mechanism against the lens proliferation is involved, except
      for TGF-beta. In this study, the authors demonstrated the enhanced expression of
      p21(WAF-1/CIP-1), a potent inhibitor against cell cycle progression, and its
      specific temporal and regional expression profiles in the LECs during the
      development of sugar cataract. Sugar cataract was induced in 6-week-old male
      Sprague-Dawley rats by feeding them on a 50% galactose-rich diet, and then the
      expression patterns of p21(WAF-1/CIP-1) mRNA and protein with the advance of the
      sugar cataract were studied. Western blot analyses showed that p21(WAF-1/CIP-1)
      expression increased throughout the period of galactose exposure, up to 21 days.
      Also, a gradual increase in the number of p21(WAF-1/CIP-1) positive cells was
      observed immunohistochemically in the course of the galactose exposure.
      Interestingly, p21(WAF-1/CIP-1) was significantly expressed in the multi-layered
      epithelium, which was observed typically in the advanced cataract. Proliferating
      cell nuclear antigen (PCNA), an indicator of cell proliferation, was also
      positive in the most multi-layered epithelial cells. In addition, transient
      expression of PCNA mRNA and its protein was noticed throughout the lens
      epithelium in the course of the sugar cataract development. Prior to the
      elevation of p21(WAF-1/CIP-1) mRNA expression, PCNA mRNA expression increased
      greatly and reached a peak according to the semiquantitative analyses using
      either the real time reverse transcription-polymerase chain reaction (RT-PCR) or
      the Southern blot analyses. Based on these observations, it is possible that
      p21(WAF-1/CIP-1) is elevated and exerts its inhibitory action against the
      proliferating epithelial cells during the development of the sugar cataract.

PMID- 11950236
TI  - Early attachment of uncultured retinal pigment epithelium from aged donors onto
      Bruch's membrane explants.
AB  - Retinal pigment epithelium (RPE) transplantation might replace cells lost as a
      consequence of choroidal neovascular membrane excision in patients with age
      related macular degeneration (AMD). Autologous transplantation of RPE cells
      harvested from a peripheral biopsy may overcome problems of immune rejection. To
      study the feasibility of autologous RPE cell transplantation, the authors
      examined the attachment of freshly harvested RPE cells from aged donors onto
      Bruch's membrane explants, debrided to (1) remove or (2) preserve the RPE
      basement membrane. Human retinal pigment epithelial sheets were harvested from
      adult donor eyes (N = 12, mean age 79.00 +/- 9.40 years) and, following
      incubation in collagenase, were mechanically fragmented into microaggregates.
      Microaggregates (approximately 120 000 cells) were seeded onto the paired
      explants (7 mm diameter) and incubated for 20 min, 1, 4, or 24 hr at 37 degrees
      C. The percent coverage of the debrided surface by microaggregates was determined
      by sampling the center of the explants with scanning electron microscopy. RPE
      microaggregate attachment to Bruch's membrane was significantly greater at all
      time points analysed in samples with intact basement membrane versus those with
      an exposed inner collagenous layer. Coverage of debridements retaining intact RPE
      basement membrane was 1.83 +/- 1.10% at 20 min, 3.54 +/- 2.14% at 1 hr, and 8.68
      +/- 2.63% at 4 hr. Coverage of debridements lacking basement membrane was 0.10 +/
      0.04% at 20 min, 0.39 +/- 0.25% at 1 hr, and 0.63 +/- 0.42% at 4 hr. Based on
      their morphologic appearance, many cells were dying as early as 1 hr following
      seeding. To increase surface coverage, the authors seeded four times the above
      number of cells and incubated the specimens for 1 hr. Coverage on explants
      lacking RPE basement membrane showed no increase in the number of cells attached
      to the inner collagenous layer. There was a significant approximately three-fold
      increase in the number of cells attached in the presence of basement membrane.
      These results indicate that if RPE cells from aged human donors are used for
      transplantation, some modification of the Bruch's membrane surface or the cells
      must be considered for cell attachment and eventual cell survival.

PMID- 11950238
TI  - The eye lens protein alphaA-crystallin of the blind mole rat Spalax ehrenbergi:
      effects of altered functional constraints.
AB  - The rudimentary eyes of the mole rat Spalax ehrenbergi have lost their visual
      function, but are still required for the control of circadian rhythms. It has
      previously been found that alphaA-crystallin, a major eye lens protein in other
      mammals, evolved much faster in the mole rat than in rodents with normal vision.
      Yet, although mole rat alphaA-crystallin seems superfluous as a lens protein, its
      rate of change is still much slower than that of pseudogenes, suggesting some
      remaining function. The authors therefore studied the structure and function of
      recombinant mole rat alphaA-crystallin. Circular dichroism (CD), tryptophan
      fluorescence and gel permeation analyses indicated that the overall structure and
      stability of mole rat alphaA-crystallin are comparable to that of rat alphaA
      crystallin. However, the chaperone-like activity of mole rat alphaA-crystallin is
      considerably lower than that of its rat orthologue. Two-dimensional NMR
      spectroscopy of mole rat alphaA-crystallin suggests that this may be in part due
      to a diminished flexibility of the C-terminal extension, which is thought to be
      important for the chaperoning capacity. Overall, mole rat alphaA-crystallin
      appears to still be a viable protein, confirming that it has some as yet elusive
      role, despite the loss of its primary lens function.

PMID- 11950237
TI  - Heterologous expression of WT and mutant photoreceptor peripherin/rds in Madin
      Darby canine kidney cells: an assessment of fusogenic function.
AB  - Peripherin/rds is proposed to function as a fusion protein within the rod outer
      segment and a fusion domain has been mapped to amino acids 311-325 within the C
      terminus. To map regions within peripherin/rds required for membrane fusion a
      series of C-terminal mutants was analyzed. Madin Darby canine kidney cells were
      transiently transfected with an Xpress or FLAG epitope tagged peripherin/rds (wt)
      and three mutants of peripherin/rds. The mutants selected were a P296T mutant
      (replacement of the proline at position 296 with a threonine) and two C-terminal
      deletion mutants (one lacking the terminal 10 amino acids, Delta10 and one
      lacking the terminal 50 amino acids, Delta50). The wt protein, the P296T and
      Delta10 mutants were detected on SDS-PAGE as 84 kDa dimers, that resolved into 38
      42 kDa monomers under reducing conditions. The Delta50 mutant showed a slightly
      increased mobility. The cellular localization of mutants differed from that of wt
      peripherin/rds. The wt Xpress-human and wt FLAG-bovine peripherin/rds were
      localized to both intracellular and plasma membranes. In contrast, the C-terminal
      deletion mutants were localized only to the intracellular membrane. The P296T
      mutant presented a still different pattern: initially the protein localized to
      intracellular membranes. Upon confluence, however, the localization appeared to
      become predominantly plasma membrane. To assess the fusion activity of the
      proteins, the cell membranes were fractionated using sucrose density gradient
      centrifugation and the various fractions identified based on immunoreactivity in
      Western blot analysis with Golgi (anti-rab 6) or plasma membrane (anti-ZO-3)
      specific marker proteins. All membrane fractions were assayed for fusion with ROS
      plasma membrane vesicles. The plasma membrane enriched fractions (isolated at
      densities of 1.08 and 1.125 g ml(-1)) containing tagged peripherin/rds and the
      Delta10 mutant promoted membrane fusion with ROS plasma membrane vesicles. In
      contrast, fusion was not detected with plasma membrane vesicles from mock
      transfected cells or the Delta50 peripherin/rds deletion mutant. Fusion was
      enhanced in a less dense fraction enriched in the P296T mutant (isolated from the
      1.04/1.02 interface) relative to wt. Fusion was dependent on the presence of
      peripherin/rds in the membranes and could be inhibited with trypsinolysis and
      competition studies with the bovine fusion peptide, PP-5. Peptide competition
      suggests that the fusion domain of human peripherin/rds is most likely identical
      to that characterized in bovine and corresponds to amino acid residues 312-326.
      The C-terminal deletion mutants have allowed us to predict the minimal region of
      the C-terminus necessary for fusion to include residues starting at number 335.
      In addition a second region important in the formation of a fusion competent
      peripherin/rds has been mapped to a region upstream of the fusion peptide domain.

PMID- 11950240
TI  - Lipid hydroperoxide stimulates subretinal choroidal neovascularization in the
      rabbit.
AB  - The authors sought to evaluate the effect of linoleic acid hydroperoxide
      (18:2/LHP) in promoting choroidal neovascularization (CNV). Albino male rabbits
      received a subretinal injection of various amounts of LHP (ranging from 5 to 200
      microg) dissolved in 50 microl of sodium borate buffer. Control eyes received the
      buffer only. Eyes were examined up to 4 weeks later with indirect ophthalmoscopy,
      fundus photography and fluorescein angiography. Animals were killed on days 3, 7,
      14 or 28, and eyes examined by light and transmission electron microscopy. In
      eyes injected with LHP of 150-200 microg, exposed areas turned white as observed
      ophthalmoscopically and showed both severe retinal and choroidal atrophy
      histologically. Neither fluorescein leakage nor CNV was found in these eyes or in
      controls. In 33 eyes injected with LHP of 100 microg or less, prominent
      fluorescein leakage was seen in three (9%) and less prominent focal leakage in
      five (15%). In 11 (46%) of the 24 eyes injected with 12.5-50 microg LHP, CNV was
      found histologically. Subretinal injection of LHP is capable of inducing CNV.

PMID- 11950239
TI  - Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo
      following alkali injury.
AB  - Previously, thymosin beta 4 (Tbeta(4)) was found to promote wound healing in full
      thickness skin wounds and heptanol debrided corneas. Here, the effect of Tbeta(4)
      was examined treatment on corneal wound healing and inflammation in vivo after
      alkali injury, a more severe wound of the eye. Corneas from 129 Sv mice were
      chemically burned with a 2 mm disc soaked in 1 N NaOH for 30 sec. Eyes were
      irrigated copiously with phosphate buffered saline (PBS) and then treated
      topically with either Tbeta(4) (5 microg/5 microl PBS) or 5 microl PBS twice
      daily. Animals were killed, the eyes were enucleated, fixed and embedded in
      plastic resin or prepared for mRNA analysis. Mouse corneas topically treated with
      5 microg of Tbeta(4) twice daily after alkali injury demonstrated accelerated re
      epithelialization at all time points and decreased polymorphonuclear leukocyte
      (PMN) infiltration at 7 days post injury (p.i.) when compared to PBS-treated
      controls. mRNA transcript levels were decreased several fold for interleukin (IL)
      lbeta, and the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP
      1beta, MIP-2 and monocyte chemoattractant protein (MCP)-1 from 1 to 7 days after
      injury in the Tbeta(4)- vs. PBS-treated corneas. Thus, Tbeta(4) may provide a new
      clinical treatment for severe traumatic corneal wound disorders by promoting
      rapid corneal wound healing and decreasing both PMN infiltration and inflammatory
      cytokine and chemokine mRNA levels.

PMID- 11950241
TI  - Safety and pharmacokinetics of intravitreal 2-methoxyestradiol implants in normal
      rabbit and pharmacodynamics in a rat model of choroidal neovascularization.
AB  - Choroidal neovascularization (CNV) is the leading cause of severe vision loss
      associated with age-related macular degeneration. As the pathogenesis of CNV
      formation is better understood, mechanism-based therapies, including the use of
      antiangiogenesis inhibitors, have been investigated. 2-methoxyestradiol (2ME2),
      an endogenous metabolite of estradiol, has been shown in the chick allantoic
      membrane model and the corneal micropocket assay to have antiangiogenic
      properties. The authors sought to determine the safety and pharmacokinetics of
      sustained-release intravitreal 2ME2 implants in normal rabbit and their efficacy
      in a rat model of CNV. 2ME2 implants were constructed using two designs: implant
      A, a silicone-based reservoir implant for the rabnbit eye, and implant B, a
      microimplant matrix design for the rat eye. In vitro release rates of both
      implants were determined. New Zealand white (NZW) rabbits had implant A placed in
      the vitreous cavity of one eye and the ocular toxicity was evaluated by clinical
      examination, serial electroretinography (ERG), and histopathology over a 28 week
      period. The steady state clearance of 2ME2 in the rabbit eye was calculated from
      in vivo release rates divided by steady state vitreous concentrations. A CNV
      model in the Brown-Norway rat was performed by injecting an adenoviral vector
      encoding human vascular endothelial growth factor in the subretinal space.
      Following the injection, a 2ME2 or sham (no drug) microimplant was placed in the
      vitreous cavity. Animals were killed over a 3 week period and the eyes examined
      for CNV by histopathology. Results showed that following a short burst, the
      release rate of implant A followed zero-order kinetics, typical of reservoir
      devices, and the cumulative release of implant B was proportional to the square
      root of time, as expected for a matrix delivery device. The safety studies in
      normal rabbit showed no ocular toxicities by clinical examination, ERG, and
      histopathology. Pharmacokinetic evaluation in the rabbit showed mean 2ME2
      vitreous levels within the therapeutic range for the inhibition of endothelial
      cell proliferation. The experimental rat model showed a significant reduction in
      CNV in eyes treated with the 2ME2 implant. In conclusion, sustained-release 2ME2
      intravitreal implants, which can be designed to deliver potentially therapeutic
      vitreous levels of 2ME2 for an extended period of time, appeared to be safe in
      normal rabbit and effective in a rat model of CNV. Sustained-release 2ME2
      intravitreal implants may hold promise in the treatment of recurrent CNV
      refractory to standard therapy.

PMID- 11950242
TI  - Brain-derived neurotrophic factor enhances neurite regeneration from retinal
      ganglion cells in aged human retina in vitro.
AB  - To investigate the capability of neurite regeneration from retinal ganglion cells
      (RGCs) in an adult human retina and to evaluate the effect of neurotrophin on the
      neurite regeneration, an in vitro model for retinal explants was developed. A
      human retina was obtained from a 70 year old patient with retrobulbar carcinoma.
      The retina was excised and the retinal explants were cultured in serum-free
      medium with or without brain-derived neurotrophic factor. The capability of
      neurite regeneration was evaluated by counting the numbers of outgrowing neurites
      outside the retinal explants. In culture without brain-derived neurotrophic
      factor (control), there was no neurite outgrowth from the retinal explants after
      2 days. And at 3 days in culture, a small number of outgrowing neurites were
      first observed outside the retinal explants. In contrast, within 24 hr in culture
      with brain-derived neurotrophic factor, there were a considerable number of
      elongating neurites with spread growth cones from the retinal explants.
      Immunohistochemical analysis revealed that these neurites were derived from RGCs.
      The addition of brain-derived neurotrophic factor increased the number of
      outgrowing neurites approximately 10-fold compared to that of the control at 3
      days in culture. The enhancement of neurite regeneration induced by brain-derived
      neurotrophic factor continued for longer than 1 week in culture. In conclusion,
      an aged human retina can regenerate neurites from RGCs in vitro and brain-derived
      neurotrophic factor significantly promotes the regeneration.

PMID- 11950243
TI  - Neuroendocrinology of song behavior and avian brain plasticity: multiple sites of
      action of sex steroid hormones.
AB  - Seasonal changes in the brain of songbirds are one of the most dramatic examples
      of naturally occurring neuroplasticity that have been described in any vertebrate
      species. In males of temperate-zone songbird species, the volumes of several
      telencephalic nuclei that control song behavior are significantly larger in the
      spring than in the fall. These increases in volume are correlated with high rates
      of singing and high concentrations of testosterone in the plasma. Several song
      nuclei express either androgen receptors or estrogen receptors, therefore it is
      possible that testosterone acting via estrogenic or androgenic metabolites
      regulates song behavior by seasonally modulating the morphology of these song
      control nuclei. However, the causal links among these variables have not been
      established. Dissociations among high concentrations of testosterone, enlarged
      song nuclei, and high rates of singing behavior have been observed. Singing
      behavior itself can promote cellular changes associated with increases in the
      volume of the song control nuclei. Also, testosterone may stimulate song behavior
      by acting in brain regions outside of the song control system such as in the
      preoptic area or in catecholamine cell groups in the brainstem. Thus testosterone
      effects on neuroplasticity in the song system may be indirect in that behavioral
      activity stimulated by testosterone acting in sites that promote male sexual
      behavior could in turn promote morphological changes in the song system.

PMID- 11950244
TI  - Integration of endocrine signals that regulate insect ecdysis.
AB  - The extremely large number of insects and members of allied groups alive today
      suggests that molting--shedding of an old cuticle--may be one of the most
      commonly performed behaviors on our planet. Removal of an old cuticle in insects
      is associated with stereotyped, species-specific patterns of behavior referred to
      as ecdysis. It has been recognized for decades that the initiation of ecdysis is
      under hormonal control, but until recently many of the key peptides that regulate
      ecdysis were unknown. The report in 1996 of a new ecdysis-triggering hormone
      (ETH) sparked an era of significant advances in our understanding of the
      regulation of molting. This article summarizes the current model of peptide
      regulation of ecdysis, a model that is based on a positive feedback loop between
      ETH and a brain peptide, eclosion hormone. Then the relationship of these
      regulatory peptides to the neural circuitry that is the ultimate driver of the
      behavior are described. Because insects can undergo both status quo (larval
      larval) and metamorphic (larval-pupal and pupal-adult) molts, differences in
      ecdysis behavior at different life stages are described and potential sources of
      these differences are identified. Most of the work described is based on studies
      of ecdysis in the hawkmoth, Manduca sexta, but results from studies of ecdysis in
      the fruit fly Drosophila melanogaster are also discussed.

PMID- 11950245
TI  - The neuroendocrine basis of social recognition.
AB  - All social relationships are dependent on an organism's ability to remember
      conspecifics. Social memory may be a unique form of memory, critical for
      reproduction, territorial defense, and the establishment of dominance hierarchies
      in a natural context. In the laboratory, social memory can be assessed reliably
      by measuring the reduction in investigation of a familiar partner relative to
      novel conspecifics. The neurohypophyseal neuropeptides oxytocin and vasopressin
      have been shown to influence a number of forms of social behavior, including
      affiliation, aggression, and reproduction. This article reviews vasopressin and
      oxytocin effects on social cognition, particularly the acquisition and retention
      of social recognition in rats and mice. Studies in rats have demonstrated that
      vasopressin in specific neural pathways, such as the lateral septum, is necessary
      for social recognition. As vasopressin facilitates recall when given after an
      initial encounter, the peptide appears important for the consolidation not the
      acquisition of a social memory. Although oxytocin has complex effects on social
      memory in rats, mice with a null mutation of the oxytocin gene are completely
      socially amnestic without other cognitive deficits evident. As oxytocin given
      centrally before but not after the initial encounter restores social recognition
      in these mutant mice, the neuropeptide appears critical for the acquisition
      rather than the consolidation phase of memory. Oxytocin's effects on social
      memory are mediated via a discrete cell population in the medial amygdala. These
      findings support the hypothesis that vasopressin and oxytocin are essential for
      social memory, although they appear to influence different cognitive processes
      and may modulate different neural systems. (c) Elsevier Science.

PMID- 11950246
TI  - A randomized controlled trial to evaluate the slow-acting symptom modifying
      effects of a regimen containing colchicine in a subset of patients with
      osteoarthritis of the knee.
AB  - OBJECTIVE: As crystals may contribute to inflammation in osteoarthritis (OA), it
      is hypothesized that colchicine may have symptom/disease modifying effects in OA.
      The objective of this study was to evaluate the symptomatic benefit of addition
      of colchicine to a regimen of intraarticular steroids and piroxicam in patients
      with knee OA with inflammation. DESIGN: 39 patients with OA of the knee with
      persisting inflammation, despite at least 2 weeks of piroxicam, were subjected to
      intraarticular steroid injection and randomly assigned to receive colchicine 0.5
      mg twice daily or placebo in a randomized, double blind, placebo-controlled trial
      over 5 months. RESULTS: VAS for index knee pain (VAS-pain) and total KGMC score
      (a modified WOMAC index) at 16 and 20 weeks were significantly better in the
      colchicine group than the corresponding scores in controls. The benefit persisted
      on multivariate analysis at 16 weeks (Hotellings T(2)=18.6, F(5,33)=3.3154,
      P=0.015). The proportion of patients who had 30% or greater response at 16 weeks
      was significantly higher in the colchicine group in VAS-pain (69% vs 15%) and
      total KGMC scores (74% vs 45%) and the significance persisted on combined
      analysis using Mantel-Haenszel test (M-H Risk=5.9, 95% C.I.: 2.08 to 16.73). At
      20 weeks, benefit of colchicine therapy was seen on pooled analysis only (M-H
      risk=3.71, 95% C.I.: 1.07=8.02). CONCLUSION: The addition of colchicine produced
      significantly greater symptomatic benefit at 16 and 20 weeks than intraarticular
      steroid and piroxicam alone in patients with knee OA with inflammation.

PMID- 11950247
TI  - Matrilin-3 in human articular cartilage: increased expression in osteoarthritis.
AB  - OBJECTIVE: Matrilin-3 is a member of the recently described matrilin family of
      extracellular matrix proteins containing von Willebrand factor A-like domains.
      The matrilin-3 subunit can form homo-tetramers as well as hetero-oligomers
      together with subunits of matrilin-1 (cartilage matrix protein). It has a
      restricted tissue distribution and is strongly expressed in growing skeletal
      tissues. Detailed information on expression and distribution of extracellular
      matrix proteins is important to understand cartilage function in health and in
      disease like osteoarthritis (OA). METHODS: Normal and osteoarthritic cartilage
      were systematically analysed for matrilin-3 expression, using
      immunohistochemistry, Western blot analysis, in situ hybridization, and
      quantitative PCR. RESULTS: Our results indicate that matrilin-3 is a mandatory
      component of mature articular cartilage with its expression being restricted to
      chondrocytes from the tangential zone and the upper middle cartilage zone.
      Osteoarthritic cartilage samples with only moderate morphological osteoarthritic
      degenerations have elevated levels of matrilin-3 mRNA. In parallel, we found an
      increased deposition of matrilin-3 protein in the cartilage matrix. Matrilin-3
      staining was diffusely distributed in the cartilage matrix, with no cellular
      staining being detectable. In cartilage samples with minor osteoarthritic
      lesions, matrilin-3 deposition was restricted to the middle zone and to the upper
      deep zone. A strong correlation was found between enhanced matrilin-3 gene and
      protein expression and the extent of tissue damage. Sections with severe
      osteoarthritic degeneration showed the highest amount of matrilin-3 mRNA, strong
      signals in in situ hybridization, and prominent protein deposition in the middle
      and deep cartilage zone. CONCLUSION: We conclude that matrilin-3 is an integral
      component of human articular cartilage matrix and that the enhanced expression of
      matrilin-3 in OA may be a cellular response to the modified microenvironment in
      the disease.

PMID- 11950248
TI  - Susceptibility to physiological concentrations of IL-1beta varies in cartilage at
      different anatomical locations on human osteoarthritic knee joints.
AB  - OBJECTIVES: To determine whether cartilage biopsies from specific regions of
      osteoarthritic knee joints differ in susceptibility to the degradative effects of
      the amounts of interleukin-1 beta (IL-1 beta; 1-10 pg/ml) found in osteoarthritic
      joints. To establish whether biopsies are sensitive to the effects of either IL-1
      beta or TNFalpha or both catabolic cytokines. METHODS: Cartilage from specified
      regions of 22 osteoarthritic knee joints was examined. Biopsies were incubated
      for 14 days without or with IL-1 beta or TNFalpha at physiological concentrations
      and GAG release into supernatants assessed. RESULTS: Variation was observed in
      susceptibility to the effects of 1-10 pg/ml IL-1 beta in biopsies from different
      sites within the same joints and the same site in different joints. The number of
      regions responding to the cytokine increased significantly (P< 0.0063, Chi square
      test) with concentration: only 10% (2/21) of all regions tested were susceptible
      to the effects of 1 pg/ml IL-1 beta, whereas 45% (9/20) were susceptible to the
      effects of 5 pg/ml and 56% (10/18) to the effects of 10 pg/ml IL-1 beta.
      Significantly fewer regions (4%, 2/47) responded to both IL-1 beta and TNFalpha
      (P< 0.047, Chi square test); biopsies from some patients responded to neither
      cytokine. CONCLUSIONS: IL-1 beta, at the low concentrations detected in joints,
      can degrade cartilage from susceptible locations. Susceptibility of some
      cartilage biopsies to the effects of either IL-1 beta and TNFalpha, but not both,
      suggests the signalling receptors for the two major catabolic cytokines are not
      usually expressed concurrently. The fact that some biopsies respond to neither
      cytokine suggests that in some patients the local concentration of inhibitors may
      be high or that other catabolic stimuli predominate. These results could have
      important implications for pharmacological intervention strategies.

PMID- 11950249
TI  - Evidence of oncotic cell death and DNA fragmentation in human hypertrophic
      chondrocytes in chondro-osteophyte.
AB  - OBJECTIVE: To investigate the population and morphology of in situ terminal
      deoxynucleotidyle transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) stain
      positive non-apoptotic chondrocytes in hypertrophic zone of human chondro
      osteophytes. MATERIALS AND METHODS: Chondro-osteophytes from osteoarthritic
      patients were obtained at joint replacement surgery. Apoptosis was verified by
      light microscopic examination of Safranin O stained sections and TUNEL stain.
      TUNEL staining was also performed on hydrophilic resin embedded semi-thin and
      ultra-thin sections combined with the treatment with streptavidin-gold
      conjugates, observed by light microscopy with silver enhancement technique (TUNEL
      LM with SE) and transmission electron microscopy (TUNEL-TEM) respectively for the
      simultaneous evaluation of cellular structure and DNA fragmentation. RESULTS: In
      paraffin embedded sections (N=18), 31.5+/-6.1% of cells in the hypertrophic zone
      were TUNEL positive, but only 3.8+/-1.2% cells in this zone showed apoptotic
      appearances with cell shrinkage and nuclear condensation. Both in TUNEL-TEM and
      TUNEL-LM with SE, gold particles, which indicate DNA fragmentation, were observed
      within the nucleus of morphologically apoptotic chondrocytes, as well as of
      disintegrated, swollen chondrocytes. CONCLUSIONS: In human chondro-osteophytes,
      hypertrophic chondrocytes might die by oncotic cell death with DNA fragmentation,
      as well as apoptosis.

PMID- 11950250
TI  - Characterization of infiltrating T cells and Th1/Th2-type cytokines in the
      synovium of patients with osteoarthritis.
AB  - OBJECTIVE: It has been suggested that osteoarthritis (OA) is induced by
      mechanical stress followed by cartilage destruction, and it is generally accepted
      that there is little involvement of an immune response in OA compared with that
      in rheumatoid arthritis (RA). We have previously found clonally expanded
      transcripts of Vbeta chain of the T cell receptor (TCR) in the synovium of
      patients with OA. To test the hypothesis that an immune response is involved in
      OA, we determined: (a) whether CD3+, CD4+, and CD8+ T-cells were infiltrating the
      synovial membrane of patients with OA; (b) the Th1/Th2-type cytokines produced at
      the protein level in the synovium of patients with OA. METHODS:
      Immunohistochemical analysis was performed to identify T-cells that infiltrated
      the synovium of patients with OA using specific antibodies against CD3+, CD4+,
      and CD8+ T-cell differential antigens, interferon-gamma (IFN-gamma as a marker
      for Th1 cells, and interleukin-4 (IL-4) as a marker for Th2 cells. RESULTS: CD4+
      T-cells were strongly detected in the sublining layer of the synovium of patients
      with OA compared with the number detected in the same synovial layer of normal
      subjects. The number of IFN-gamma+ cells was significantly higher than that of IL
      4+ cells in the synovium of patients with OA (P< 0.05). CONCLUSION: These
      observations suggest that Th1 cells predominate in the synovium of patients with
      OA, which clearly indicates that immune regulation occurs and may play critical
      roles in inflammation and cartilage destruction in patients with OA.

PMID- 11950251
TI  - Steady progression of osteoarthritic features in the canine groove model.
AB  - OBJECTIVE: Recently we described a canine model of osteoarthritis (OA), the
      groove model with features of OA at 10 weeks after induction, identical to those
      seen in the canine anterior cruciate ligament transection (ACLT) model. This new
      model depends on cartilage damage accompanied by transient intensified loading of
      the affected joint. The present study evaluates this groove model at 20 and 40
      weeks after induction, to assess whether the osteoarthritic features progress in
      time. METHODS: Grooves were made in the femoral condyles of one knee without
      damaging the subchondral bone. After surgery the dogs were forced to load the
      experimental joint 3 days per week (4 hours/day) for 20 weeks by fixing the
      contralateral control limb to the trunk. After 20 weeks and 40 weeks (the last 20
      weeks normal loading) joints were analysed for biochemical and histological
      features of OA. RESULTS: All biochemical cartilage parameters were indicative of
      OA and all these parameters suggested a slow progression of degeneration over
      time from 20 to 40 weeks after induction, statistically significant for synthesis
      and content of proteoglycans as well as Mankin grade. Synovial inflammation,
      which was mild, diminished slightly in time. CONCLUSION: The degenerative joint
      damage in the canine groove model is slowly progressive over time in the first
      year. The cartilage degeneration is induced by a one-time trauma and is not
      primarily mediated by synovial inflammation, which gives this model unique
      characteristics compared to presently available models for studying early
      osteoarthritic features in vivo. In the groove model the effect of treatment of
      cartilage damage is not counteracted by permanent joint instability or hampered
      by inflammation. Therefore, the model might be more sensitive to detect effects
      of therapy, aimed at cartilage protection and repair.

PMID- 11950252
TI  - Efficacy and safety of the COX-2 specific inhibitor valdecoxib in the management
      of osteoarthritis of the hip: a randomized, double-blind, placebo-controlled
      comparison with naproxen.
AB  - OBJECTIVE: Non-steroidal antiinflammatory agents are commonly used to treat pain
      and inflammation associated with osteoarthritis (OA), but have poor
      gastrointestinal (GI) tolerability. This study compared the efficacy of the COX-2
      specific inhibitor valdecoxib with naproxen and placebo, in treating symptomatic
      OA of the hip. DESIGN: This multicenter, randomized, double-blind 12-week study
      compared the efficacy and tolerability of single daily doses of valdecoxib 5 mg
      and 10 mg with placebo or naproxen 500 mg BID. Efficacy was assessed by Patient's
      and Physician's Global Assessment of Arthritis, and the WOMAC (Western Ontario
      and McMasters) OA Individual and Composite Indices. The incidence of adverse
      events was monitored throughout the study. RESULTS: Valdecoxib was clinically and
      statistically superior to placebo for Patient's and Physician's Global Assessment
      of Arthritis and for all WOMAC OA Indices over the 12 week study period (P<or=
      0.05). Valdecoxib 10 mg was similar to naproxen in terms of efficacy, and
      demonstrated greater numerical improvements compared with valdecoxib 5 mg.
      Valdecoxib 5 mg and 10 mg demonstrated similar tolerability compared to placebo
      and a lower incidence of GI-related adverse effects compared with naproxen.
      CONCLUSIONS: Single daily doses of valdecoxib 5 mg and 10 mg were similar to
      naproxen and superior to placebo, in treating symptomatic OA of the hip. Both
      doses of valdecoxib were well tolerated and demonstrated improved GI tolerability
      compared to naproxen.

PMID- 11950253
TI  - The influence of the pericellular microenvironment on the chondrocyte response to
      osmotic challenge.
AB  - OBJECTIVE: To examine whether differences in the pericellular microenvironment of
      different chondron preparations influence the chondrocyte volume regulatory
      response to experimental osmotic challenge. DESIGN: Mechanically extracted
      chondrons (MC), enzymatically extracted chondrons (EC) and isolated chondrocytes
      (IC) were seeded into agarose and sampled at 1, 3 and 7 days. Samples mounted in
      a perfusion chamber were subjected to osmotic challenge. The cross-sectional
      areas of the chondrocyte and pericellular microenvironment were measured under
      isotonic, hypertonic and hypotonic conditions, and percentage change calculated.
      Separate samples were immunolabeled for type VI collagen and keratan sulfate.
      RESULTS: Initially, the microenvironment of MC represented 60% of the chondron
      area and was occupied by type VI collagen and keratan sulfate. In EC, the
      microenvironment comprised 18% of the chondron area with narrow bands of type VI
      collagen and keratan sulfate. IC had no visible microenvironment, with small
      amounts of type VI collagen and keratan sulfate present. All preparations
      sequestered additional pericellular macromolecules during culture. Under isotonic
      conditions, the EC and IC chondrocytes were larger than those of MC. All
      chondrocytes shrank under hypertonic conditions and swelled under hypotonic
      conditions. MC were the least responsive, displaying the most efficient volume
      regulation. IC showed the largest response initially but this decreased with
      time. EC exhibited intermediate responses that decreased as the microenvironment
      increased in size. CONCLUSIONS: The composition and structural integrity of the
      pericellular microenvironment do influence the cellular response to experimental
      osmotic challenge. This suggests that the microenvironment functions in situ to
      mediate the chondrocyte response to physicochemical changes associated with joint
      loading.

PMID- 11950255
TI  - Severity of medial meniscus damage in the canine knee after anterior cruciate
      ligament transection.
AB  - OBJECTIVE: To examine the relationship between the severity of cartilage damage
      and the severity of meniscus damage after transection of the anterior cruciate
      ligament (ACLT) in adult dogs. DESIGN: Data were obtained from 40 dogs which
      underwent ACLT and from three additional sham-operated dogs that were subjected
      to arthrotomy but not ligament transection. Joint pathology was analysed 12, 24
      or 32 weeks after surgery. The severity of damage to the articular cartilage on
      the femoral condyle and tibial plateau was graded with a scoring system based on
      that of the Societe Francaise d'Arthroscopie and meniscus damage was graded on a
      0-4 scale. RESULTS: No damage to the meniscus or articular cartilage was observed
      12 weeks after surgery in the dogs subjected only to arthrotomy. In contrast,
      tears of the medial meniscus were observed in two of 10 (20%) dogs examined 12
      weeks after ACLT. The incidence of severe tears increased to 86% and 84% after 24
      weeks and 32 weeks, respectively. Damage to the lateral meniscus was mild, with
      only 7.5% of all dogs with a cruciate-deficient knee having a bucket handle or
      complete tear. Most of the unstable knees exhibited ulceration of the articular
      cartilage of the femoral condyles and tibial plateaus 12 weeks (mean chondropathy
      score+/-standard deviation 11.9+/-8.5, N=10), 24 weeks (7.9+/-5.0, N=7), and 32
      weeks (7.1+/-5.5, N=23) after ACLT. The mean chondropathy scores for the tibial
      plateaus were similar to those for the femoral condyles. No correlation was
      apparent between the severity of cartilage damage and of meniscus damage for
      either joint surface. CONCLUSION: Damage to the medial meniscus is a consistent
      feature of the pathology which develops in the canine knee after ACLT, but the
      severity of cartilage damage is not correlated with the severity of meniscal
      damage.

PMID- 11950254
TI  - Fibroblast growth factor-18 is a trophic factor for mature chondrocytes and their
      progenitors.
AB  - OBJECTIVE: The aim of this study was to examine the effects of recombinant human
      Fgf18 on chondrocyte proliferation and matrix production in vivo and in vitro. In
      addition, the expressions of Fgf18 and Fgf receptors (Fgfr) in adult human
      articular cartilage were examined. METHODS: Adenovirus-mediated transfer of Fgf18
      into murine pinnae and addition of FGF18 to primary cultures of adult articular
      chondrocytes were used to assess the effects of FGF18 on chondrocytes. In situ
      hybridization was used to examine the expression of Fgf18 and Fgfr s in adult
      human articular cartilage. RESULTS: Expression of Fgf18 by adenovirus-mediated
      gene transfer in murine pinnae resulted in a significant increase in chondrocyte
      number. Chondrocytes were identified by staining with toluidine blue and a
      monoclonal antibody directed against type II collagen. Fgf18, Fgfr 2-(IIIc), Fgfr
      3-(IIIc), and Fgfr 4 mRNAs were detected within these cells by in situ
      hybridization. The nuclei of the chondrocytes stained with antibodies to PCNA and
      FGF receptor (FGFR) 2. Addition of FGF18 to the culture media of primary
      articular chondrocytes increased the proliferation of these cells and increased
      their production of extracellular matrix. To assess the receptor selectivity of
      FGF18, BaF3 cells stably expressing the genes for the major splice variants of
      Fgfr1-3 were used. Proliferation of cells expressing Fgfr 3-(IIIc) or Fgfr 2
      (IIIc) was increased by incubation with FGF18. Using FGFR-Fc fusion proteins and
      BaF3 cells expressing Fgfr 3-(IIIc), only FGFR 3-(IIIc)-Fc, FGFR 2-(IIIc)-Fc or
      FGFR 4-Fc reduced FGF18-mediated cell proliferation. Expression of Fgf18, Fgfr 3
      (IIIc) and Fgfr 2-(IIIc) mRNAs was localized to chondrocytes of human articular
      cartilage by in situ hybridization. CONCLUSION: These data demonstrate that Fgf18
      can act as a trophic factor for elastic chondrocytes and their progenitors in
      vivo and articular chondrocytes cultured in vitro. Expression of Fgf18 and the
      genes for two of its receptors in chondrocytes suggests that Fgf18 may play an
      autocrine role in the biology of normal articular cartilage.

PMID- 11950256
TI  - Effects of TNFalpha-antagonists on nitric oxide production in human cartilage.
AB  - OBJECTIVE: Nitric oxide (NO) produced by cartilage and synovial membrane is
      implicated in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis
      (RA). In inflamed joints NO is synthesized in response to proinflammatory
      cytokines and it is involved in the joint destruction. The aim of the present
      study was to investigate the effects of TNFalpha-antagonists infliximab and
      etanercept on NO production in human cartilage. DESIGN: Cartilage specimen
      obtained from OA patients undergoing knee replacement surgery were studied for
      iNOS expression and NO production in organ culture to allow intact chondrocyte
      matrix interactions. TNFalpha and soluble TNFalpha receptor release was measured
      by ELISA. RESULTS: Osteoarthritic cartilage produced NO spontaneously and its
      production was enhanced by proinflammatory cytokines TNFalpha (tumor necrosis
      factor alpha), IL-1beta (interleukin-1beta), IL-17 (interleukin-17) and by
      bacterial lipopolysaccharide (LPS). TNFalpha-antagonists infliximab and
      etanercept inhibited TNFalpha-induced NO production in a dose dependent manner
      but they had no effect on IL-1beta-, IL-17- and LPS-stimulated NO synthesis.
      TNFalpha and soluble TNFalpha receptors (sTNFRI and sTNFRII) were produced by
      human osteoarthritic cartilage. A neutralizing antibody against soluble TNFRI
      enhanced spontaneous NO production whereas an antibody against soluble TNFRII had
      no effect. CONCLUSIONS: TNFalpha-antagonists infliximab and etanercept suppressed
      TNFalpha-induced NO production. This effect was not seen on IL-1-, IL-17- or LPS
      induced NO production suggesting that TNFalpha is not an autacoid mediator in
      these processes. The studies with neutralizing antibodies against soluble TNFRI
      suggest that endogenous cartilage-derived TNFalpha-antagonists modulate NO
      production in osteoarthritic cartilage.

PMID- 11950273
TI  - Oxidative damage to nucleic acids in human prion disease.
AB  - Recently, several studies proposed a physiological role for the cellular prion
      protein (PrP(c)) in defense against oxidative stress. Since the pathogenesis of
      prion disease necessarily involves a disturbance of PrP(c) homeostasis, we
      hypothesized that such diseases would be associated with concomitant disturbances
      in oxidative balance. In support of such a notion, in this study we show
      increased oxidative damage to nucleic acids in affected brains of patients with
      Creutzfeldt-Jakob disease. These data suggest that damage by free radicals is a
      likely cause for neurodegeneration in human prion disease, and antioxidants are a
      potential therapy for these disorders. Further, our data support the hypothesis
      that loss of the anti-oxidant function of PrP(c) plays a key role in the
      pathogenesis of these disorders.

PMID- 11950274
TI  - The estrogen receptor is not essential for all estrogen neuroprotection: new
      evidence from a new analog.
AB  - We synthesized an estrogen analog, ZYC-5, lacking activity at the classical
      estrogen receptor and examined its neuroprotective potential against necrosis
      induced by N-methyl-d-aspartate (NMDA) and apoptosis/necrosis induced by the NMDA
      receptor antagonist (+)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid
      (CPP). ZYC-5 protected cortical neurons in a dose-dependent manner, and the
      neuroprotection was more robust than with 17beta-estradiol. The effect of ZYC-5
      was not mediated by the classical estrogen receptor, because it was unaffected by
      the antagonists 4-hydroxytamoxifen and ICI 182,780. The ZYC-5 protection against
      excitotoxicity was not directly mediated through the NMDA receptor, because there
      was no effect of ZYC-5 on NMDA current or the intracellular calcium increase
      induced by NMDA. Results obtained with the free-radical-sensitive dye,
      dihydroethidium, suggested that the neuroprotection of ZYC-5 was partly related
      to its radical scavenging properties. Although some of estrogen's neuroprotective
      effects may depend upon the estrogen receptor, our results suggest the
      possibility of neuroprotection without hormonal side effects.

PMID- 11950276
TI  - Human and murine ApoE markedly alters A beta metabolism before and after plaque
      formation in a mouse model of Alzheimer's disease.
AB  - The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's
      disease (AD), perhaps through effects on amyloid-beta (Abeta) metabolism.
      Detailed analyses of various Abeta parameters in aging APP(V717F+/-) transgenic
      mice expressing mouse apoE, no apoE, or human apoE2, apoE3, or apoE4 demonstrate
      that apoE facilitates, but is not required for, Abeta fibril formation in vivo.
      Human apoE isoforms markedly delayed Abeta deposition relative to mouse apoE,
      with apoE2 (and apoE3 to a lesser extent) having a prolonged ability to prevent
      Abeta from converting into fibrillar forms. Isoform-specific effects of human
      apoE on Abeta levels and neuritic plaque formation mimicked that observed in AD
      (E4 > E3 > E2). Importantly, observation of an apoE-dependent decrease in percent
      soluble Abeta and enrichment of Abeta in membrane microdomains prior to Abeta
      deposition indicates that apoE influences Abeta metabolism early in the
      amyloidogenic process and provides a possible novel mechanism by which apoE
      affects AD pathogenesis.

PMID- 11950275
TI  - Akt phosphorylation and neuronal survival after traumatic brain injury in mice.
AB  - The serine-threonine kinase, Akt, is involved in the survival signaling pathways
      in many cell systems. The present study examined phosphorylation of Akt at serine
      473 and DNA fragmentation after traumatic brain injury (TBI) in mice.
      Immunohistochemistry showed phospho-Akt was decreased in the injured cortex 1 h
      after TBI, whereas it was temporally increased at 4 h in the perifocal damaged
      cortex. In the CA1 region of the hippocampus, phospho-Akt was increased after
      TBI. Western blot analysis showed that Akt was significantly decreased as early
      as 1 h after trauma; however, the phosphorylation was accelerated at 4 h. Double
      staining with phospho-Akt and phospho-BAD or phospho-GSK-3beta revealed the
      colocalization of phospho-Akt and downstream elements. Double staining with
      phospho-Akt and terminal deoxynucleotidyl transferase-mediated uridine 5'
      triphosphate-biotin nick end-labeling showed different cellular distributions
      after TBI. The present study implicates Akt phosphorylation in the signaling
      pathways that are involved in cell survival after TBI.

PMID- 11950277
TI  - Metallothionein-1+2 deficiency increases brain pathology in transgenic mice with
      astrocyte-targeted expression of interleukin 6.
AB  - Transgenic expression of IL-6 under the control of the GFAP gene promoter (GFAP
      IL6 mice) in the CNS causes significant damage and alters the expression of many
      genes, including the metallothionein (MT) family, especially in the cerebellum.
      The crossing of GFAP-IL6 mice with MT-1+2 knock out (MTKO) mice provided evidence
      that the increased MT-1+2 expression normally observed in the GFAP-IL6 mice is an
      important mechanism for coping with brain damage. Thus, the GFAP-IL6xMTKO mice
      showed a decreased body weight gain and an impaired performance in the rota-rod
      test, as well as a higher upregulation of cytokines such as IL-6, IL-1alpha,beta,
      and TNFalpha and recruitment and activation of macrophages and T cells throughout
      the CNS but mainly in the cerebellum. Clear symptoms of increased oxidative
      stress and apoptotic cell death caused by MT-1+2 deficiency were observed in the
      GFAP-IL6xMTKO mice. Interestingly, MT-1+2 deficiency also altered the expected
      frequency of the offspring genotypes, suggesting a role of these proteins during
      development. Overall, the results suggest that the MT-1+2 proteins are valuable
      factors against cytokine-induced CNS injury.

PMID- 11950278
TI  - Hippocampal A beta 42 levels correlate with spatial memory deficit in APP and PS1
      double transgenic mice.
AB  - We investigated the role of hippocampal amyloid pathology in spatial learning
      impairment of a new mouse line carrying mutated human amyloid precursor protein
      (APP) and presenilin-1 (PS1) transgenes. The APP + PS1 mice were tested in
      spatial navigation in the water maze and in position discrimination in the T-maze
      at ages of 3-4 and 11-12 months, before and after the appearance of first amyloid
      plaques. The APP + PS1 mice were impaired in water maze acquisition and retention
      only at the age of 11-12 months, but performed equally to controls in the T-maze
      task at both ages. In the impaired older age group, the levels of total Abeta1-42
      in the hippocampus of APP + PS1 mice correlated negatively with the retention
      score. Here we show for the first time that the age-dependent impairment in
      memory retention in the traditional water maze of APP + PS1 mice correlates with
      the amount of total Abeta in hippocampus even at a stage when the amyloid
      deposits cover less than 1% of the hippocampal volume.

PMID- 11950279
TI  - Understanding organic gas-phase anion molecule reactions.
AB  - Although ionic reactions in the gas phase seem on the surface to be totally
      different from those in solution (e.g., they typically occur about 10(12) times
      more rapidly than their solution analogues and go about as fast at 10 K as they
      do at room temperature), they can, in fact, exhibit subtle steric, electronic,
      and isotopic effects. In this Perspective, we show how these differences arise,
      explain why gas-phase ion reactions can be both fast and selective, and discuss
      when they can and cannot be classified as "hot" reactions. We also give examples
      of the use of these reactions to devise new synthetic pathways, investigate
      reaction mechanisms, and generate important thermochemical data such as bond
      dissociation energies.

PMID- 11950280
TI  - Reaction between N-alkylhydroxylamines and chiral enoate esters: more
      experimental evidence for a cycloaddition-like process, a rationale based on DFT
      theoretical calculations, and stereoselective synthesis of new enantiopure beta
      amino acids.
AB  - The reactions between N-benzyl- and N-methylhydroxylamine and chiral enoate
      esters, derived from D-glyceraldehyde and (-)-verbenone, respectively, have been
      investigated. Theoretical calculations show that the most favorable mechanism
      involves the concerted cycloaddition of the hydroxylamine to the substrate. This
      result is in good agreement with the stereospecificity observed when the
      trisubstituted olefins are used. The open-chain adducts have been isolated when
      the processes are carried out at low temperatures and for short reaction times.
      These compounds evolve to the corresponding isoxazolidinones on standing at room
      temperature or under acid catalysis. The high pi-facial diastereoselection has
      been rationalized on the basis of steric effects induced by the dioxolane ring
      for D-glyceraldehyde derivatives or by the cyclobutane gem-dimethyl substitution
      for esters prepared from (-)-verbenone. As an application of these reactions, new
      beta-amino acids have been synthesized in a highly efficient and stereocontrolled
      manner.

PMID- 11950281
TI  - SmI(2)-mediated cyclizations of derivatized beta-lactams for the highly
      diastereoselective construction of functionalized prolines.
AB  - A series of C4-keto-functionalized 1-[(benzoyloxy)(ethoxycarbonyl)methyl]-2
      azetidinones were prepared and studied for their tendency to undergo a
      Reformatsky-type cyclization to fused bicyclic or tricyclic beta-lactams with the
      single-electron reducing agent samarium diiodide. Whereas the azetidinone 21a
      underwent reductive cyclization, affording the potent antibiotic sanfetrinem's
      tricyclic [4.5.6] core structure as the major component, all other examples
      tested resulted in cyclization followed by an N to O acyl migration involving
      cleavage of the beta-lactam ring as the favored pathway. Highly functionalized
      proline derivatives were therefore accessed as single diastereomers through the
      reductive cyclization of benzoates 21b, 22, 23a,b, 24b, and 25-28. Pertinent for
      the success of these cyclizations was the addition of 1 equiv of tert-butyl
      alcohol, allowing for the protonation of the basic amide derivative obtained
      after the acyl migration step. The diastereoselectivities of these reactions
      deviate from those of similar cyclizations involving the corresponding lithium
      enolate. This divergence could be rationalized by the coordination of the metal
      ion of the samarium(III) enolate intermediate to the beta-lactam amide
      functionality in the cyclization step, which may not be possible for lithium
      enolates.

PMID- 11950282
TI  - Calcium peroxide diperoxohydrate as a storable chemical generator of singlet
      oxygen for organic synthesis.
AB  - Calcium peroxide diperoxohydrate (CaO(2).2H(2)O(2)) is an environmentally
      friendly generator of singlet oxygen ((1)O(2), (1)Delta(g)) that can be used in
      organic synthesis as an alternative to the regular photochemical method. This
      compound produces (1)O(2) in various solvents and can be easily recovered by
      filtration for further regeneration. Both monitoring of (1)O(2) luminescence at
      1270 nm and specific trapping have shown that CaO(2).2H(2)O(2) can be stored for
      several days at -80 degrees C and that the yield of (1)O(2) is equal to 25%.
      Oxidation of typical organic substrates in methanol or THF through [4 + 2] or [2
      + 2] cycloaddition and ene reaction have been carried out on a preparative scale
      with total conversion and selectivity.

PMID- 11950283
TI  - The intriguing reactivity of functionalized beta-amino alcohols with glyoxal:
      application to a new expedient enantioselective synthesis of trans-6
      alkylpipecolic acids.
AB  - New beta-amino alcohols possessing a vinylsilane moiety were reacted with glyoxal
      to produce lactones that were transformed in three steps in enantiopure pipecolic
      acid derivatives. The key step was a totally diastereoselective ene-iminium
      cyclization, whose mechanism can be viewed as a direct cyclization of the
      vinylsilane moiety onto the iminium ion. The reactivity of two beta-amino
      alcohols having an allylsilane terminator was also examined. Their difference of
      reactivity toward glyoxal can be ascribed to the intervention of a carbocation,
      which presents a behavior that differs according to the position of the
      trimethylsilyl group.

PMID- 11950284
TI  - Photoinduced electron transfer in a supramolecular species building of mono-6-p
      nitrobenzoyl-beta-cyclodextrin with naphthalene derivatives.
AB  - Photoinduced electron transfer was observed in the supramolecular complexes of p
      nitrobenzoyl-beta-cyclodextrin (NBCD) with a number of naphthalene derivatives,
      which were stabilized clearly via hydrophobic interactions in aqueous solution.
      Both steady-state and time-resolved fluorescence measurements were conducted,
      which revealed that there were two routes of electron transfer, i.e., electron
      transfer between the free donor and free acceptor in solution and electron
      transfer between the donor and acceptor bound in a supramolecular assembly. The
      evidence collected demonstrates that the latter route was very efficient. As a
      result, the rate and quantum yield of the fluorescence quenching in the present
      supramolecular system were appreciably large.

PMID- 11950285
TI  - Designing new chiral ketone catalysts. Asymmetric epoxidation of cis-olefins and
      terminal olefins.
AB  - This paper describes a new class of chiral oxazolidinone ketone catalyst for
      asymmetric epoxidation. High ee values have been obtained for a number of cyclic
      and acyclic cis-olefins. The epoxidation was stereospecific with no isomerization
      observed in the epoxidation of acyclic systems. Encouragingly high ee values have
      also been obtained for a number of terminal olefins. Mechanistic studies show
      that electronic interactions play an important role in stereodifferentiation.

PMID- 11950286
TI  - Lead tetraacetate mediated one-pot multistage transformations: theoretical
      studies on the diverging behavior in the Hajos-Parrish and Wieland-Miescher
      series.
AB  - A computational approach to the proposed mechanistic rationale of the lead
      tetraacetate mediated oxidative cleavage of selected unsaturated diols in the
      hydrindenediol (derived from the Hajos-Parrish ketone, abbreviated as HP) and
      octalindiol (derived from the Wieland-Miescher ketone, abbreviated as WM) series
      is presented. These two unexpected cascade-type transformations have been found
      to yield structurally different products despite the similarities in the starting
      compounds 1-HP and 1-WM, which differ only by the number of carbon atoms in the
      cycloalkane rings. The final product in the HP series is the complex ring
      expanded molecule iii-6, while the final product in the WM series is the ring
      expanded bisacetoxy diacetal 7. Calculations carried out at the B3LYP/6-31G level
      have revealed the fact that the transformations of i-6 to ii-6 and of i-7 to ii-7
      are endothermic by 19.93 and 4.20 kcal/mol, respectively. The isomerization of
      compounds i to ii is more endothermic in the case of the HP series. Furthermore,
      calculations have shown the transformation of i to ii to be kinetically less
      favored in the HP series than in its analogue WM series. The activation barrier
      for the transformation of i-6 to ii-6 is calculated to be 22.09 kcal/mol, whereas
      the corresponding barrier in the WM series is 13.77 kcal/mol. The thermodynamic
      features of the reactions support the experimental findings as well: 7 is
      calculated to be more stable than iii-7, and iii-6 is more stable than 6, as
      expected. The diverging behavior in the mechanism of the interconversion of i to
      ii has been attributed to the stabilization of the positive charge by a carbonyl
      oxygen in ii-7 due to the flexibility of the seven-membered ring in contrast to
      the rigidity of the six-membered ring.

PMID- 11950287
TI  - Condensed thiophenes and selenophenes: thionyl chloride and selenium oxychloride
      as sulfur and selenium transfer reagents.
AB  - 3,4-Cyanomethyl substituted thiophenes reacted with thionyl chloride in the
      presence of base to give dicyano substituted thieno(3,4-c)thiophenes. The use of
      selenium oxychloride furnished the corresponding cyano substituted seleno(3,4
      c)thiophene. 1,2-Phenylenediacetonitriles gave the corresponding cyano
      substituted benzo(c)thiophenes and benzo(c)selenenophenes, respectively, upon
      reaction with thionyl chloride and selenium oxychloride in the presence of base.

PMID- 11950289
TI  - Synthesis of pyrroloquinolines as indole analogues of flavonols.
AB  - 7-Acetyl-4,6-dimethoxy-3-phenylindole 10 was converted into a range of 7-indolyl
      chalcones 13 by reaction with aryl aldehydes under basic conditions. Oxidation of
      the chalcones 13 with alkaline hydrogen peroxide gave the isolable epoxides 14,
      which were cyclized with further base treatment into the indole flavonols, or 5
      hydroxy-6-oxopyrroloquinolines 15. The related compounds 25 and 26, examples of
      indole flavanones and flavones, respectively, were also synthesized. UV
      spectroscopic comparisons between flavonoids and indole flavonoids are discussed.

PMID- 11950288
TI  - Ru(II)-catalyzed cascade reactions in stereocontrolled construction of rigid as
      indacene-bridged bis(alpha-amino acid) derivatives.
AB  - The key construction in the preparation of as-indacene-bridged bis(alpha-amino
      acid) derivatives was effected by a Ru(II)-catalyzed RCM cascade reaction of
      appropriately substituted triynes. The latter were available after stepwise and
      stereocontrolled alkynylations of (2R)-2,5-dihydro-2-isopropyl-3,6
      dimethoxypyrazine as chiral auxiliary. The regio- and stereochemical
      transformations have been verified by a single-crystal X-ray analysis.

PMID- 11950290
TI  - Intramolecular Diels-Alder reactions using alpha-methylene lactones as
      dienophile.
AB  - Several dienals were prepared and reacted in the presence of zinc metal with
      ethyl 2-bromomethylacrylate to provide in a Reformatsky-like reaction alpha
      methylene lactones carrying a dienyl side chain. Thermolysis of these compounds
      (11, 21, 29, and 37) gave in an intramolecular Diels-Alder reaction the
      corresponding tricyclic cycloadducts (51, 52, 53, and 54). The cycloadditions
      took place with good diastereoselectivity and yields. The stereochemistry of the
      major isomer is in accordance with an endo transition state for cycloadducts 51,
      52, and 54. In one instance (compound 58), the structure was supported by X-ray
      crystallography. In contrast to the other substrates, the nonatriene 29 cyclized
      to the exo product 53exo. The stereochemical situation could also be proven by
      NOESY NMR. However, the intramolecular Diels-Alder reaction did not work with
      furan as dienophile (compound 41) and substrate 50 featuring a densely
      functionalized tether connecting diene and alpha-methylene lactone.

PMID- 11950291
TI  - Transition-metal-promoted hydroboration of alkenes: a unique reversal of
      regioselectivity.
AB  - When hydroboration of 1-octene is carried out in the presence of catalytic
      amounts of rhodium trichloride followed by the usual oxidation (hydrogen peroxide
      in aqueous alkali), only minor proportions of 1-octanol (2.4%) are formed
      accompanied by very significant amounts of 2- (17.4%), 3- (36.9%), and 4-octanol
      (43.3%). These product compositions are obtained in good overall yield when the
      borane-THF complex is slowly added to a stirred solution of 1-octene in THF
      solvent containing the rhodium trichloride. Isomerization of 1-octene to 2-, 3-,
      and 4-octene in the presence of rhodium trichloride alone is far too slow to
      account for the foregoing results. The mechanism likely involves multiple and
      reversible addition/elimination of a Rh-activated B-H species across the double
      bonds.

PMID- 11950292
TI  - Synthesis, structures, and strain energies of dispirophosphiranes. Comparisons
      with dispirocyclopropanes.
AB  - Six novel dispirophosphirane complexes have been synthesized from the reaction of
      bicycloalkylidenes with the electrophilic phosphinidene complex PhPW(CO)(5). They
      contain a central phosphirane ring, which is spirofused on one side to a
      cyclopropane or cyclobutane ring and on the other side with a three-, four-, five
      , or six-membered ring. Their crystal structures and MP2/6-31G-computed
      geometries for simplified parent systems suggest that spirofusion with small
      rings results in a tightening of the central three-membered phosphaheterocycle,
      while spirofusion with larger rings results in a relaxation of the phosphirane
      geometry. Similar theoretical predictions are made for the corresponding
      annulated hydrocarbons. Strain energies for both the hydrocarbon and phosphorus
      series of structures have been calculated at G3(MP2). Whereas the [3]triangulane
      hydrocarbon and phospha[3]triangulane have a significant excess strain of 8.1 and
      5.2 kcal/mol per spiroatom, respectively, the excess strain for systems
      spirofused with larger rings are negligible for the hydrocarbons and even
      negative for the phosphorus-containing species because of hyperconjugative
      stabilization.

PMID- 11950293
TI  - Triorganostannylation of halo- and dihaloadamantanes and 5-chloro-2-adamantanone
      in liquid ammonia by the S(RN)1 mechanism. Relative reactivity of nucleophiles
      and bridgehead halides.
AB  - The reactions of 1-bromo-, 1-iodo-, 2-bromo-, 1,3-dibromo-, and 1,4
      dibromoadamantane with Me(3)Sn(-) ions were studied in liquid ammonia. The
      photostimulated reaction of 1-haloadamantane (1-XAd, X = Br, I) or 2-BrAd with
      Me(3)Sn(-) ions gave in a few minutes excellent yields of the substitution
      products. The 1,3-dibromo- and 1,4-dibromoadamantane with Me(3)Sn(-) ions also
      reacted very fast under irradiation to give the disubstitution product in good
      yields. In competition experiments, 1-ClAd is 5.3 times more reactive than 5
      chloro-2-adamantanone (9) toward Me(3)Sn(-) ions in liquid ammonia. When the
      nucleophile is the Ph(2)P(-) ion, 1-ClAd reacts 2.4 times faster than 9. This is
      the first time that no redox catalysis was observed when the bridgehead compound
      bears a carbonyl group as a pi acceptor. On the other hand, the nucleophile
      Me(3)Sn(-) ion was ca. >1000 times more reactive than Ph(3)Sn(-) ions toward 1
      adamantyl radicals, in contrast to the behavior of aryl radicals, where both
      nucleophiles have the same reactivity.

PMID- 11950294
TI  - First synthesis of the antifungal oidiolactone C from trans-communic acid:
      cytotoxic and antimicrobial activity in podolactone-related compounds.
AB  - The synthesis of the fungicide oidiolactone C starting from diterpenic trans
      communic acid was carried out with an overall yield of 11.7%. The key step in the
      process consists of a new bislactonization reaction catalyzed by Pd(II), which
      gives rise to the podolactone-type tetracyclic skeleton from a norlabdadienedioic
      acid. We also carried out a study of the structure-biological activity of
      different natural podolactones and their synthetic precursors. Thus, the highest
      cytotoxic activity was found in dienic dilactones with ether-type substitutions
      on C-17, whereas the closure of the gamma-lactone ring is not critical for
      presenting a maximal antimicrobial activity.

PMID- 11950296
TI  - Endo-oxacyclizations of polyepoxides: biomimetic synthesis of fused polycyclic
      ethers.
AB  - Boron trifluoride-etherate promotes the endo-selective oxacyclization of
      polyepoxides derived from various acyclic terpenoid polyalkenes, including
      geraniol, farnesol, and geranylgeraniol, providing an efficient and
      stereoselective synthesis of substituted oxepanes and fused polyoxepanes. The
      mechanism of the oxacyclization reaction probably involves intramolecular
      nucleophilic addition of epoxide oxygen to open another epoxide that is activated
      as an electrophile by the Lewis acid. These oxacyclizations proceed
      stereospecifically with inversion of configuration upon opening of each epoxide
      to provide trans-fused polycyclic products. The oxacyclization cascade is
      terminated by a tethered nucleophile, which may be the carbonyl oxygen of a
      ketone, ester, or carbonate, or a trisubstituted alkene. The best oxacyclization
      yields are generally observed with tert-butyl carbonate as the terminating
      nucleophile, although in some cases the oxacyclization products include formation
      of tert-butyl ethers as a minor product. The oxacyclization transformations
      described herein may mimic ring-forming steps in the biosynthesis of trans-syn
      trans-fused polycyclic ether marine natural products.

PMID- 11950295
TI  - Synthesis of labeled 1-amino-2-methylenecyclopropane-1-carboxylic acid, an
      inactivator of 1-aminocyclopropane-1-carboxylate deaminase.
AB  - 1-Amino-2-methylenecyclopropane-1-carboxylic acid (2-methylene-ACC) is an
      irreversible inhibitor for a bacterial enzyme, 1-aminocyclopropane-1-carboxylate
      (ACC) deaminase, which catalyzes the conversion of ACC to alpha-ketobutyrate and
      ammonia. The inactivation has been proposed to proceed with the ring scission
      induced by an addition of an enzyme nucleophile, resulting in the formation of a
      reactive turnover product that then traps an active-site residue. To gain further
      insight into this unique enzymatic reaction, the tritiated 2-methylene-ACC was
      prepared and incubated with ACC deaminase to locate and identify the entrapped
      amino acid residue. The synthesis of this radiolabeled compound and the results
      of its incubation with ACC deaminase are reported in this paper.

PMID- 11950297
TI  - A mechanistic study of photocyanation of pyrene in oil-in-water emulsion systems.
AB  - A highly efficient one-step photocyanation reaction of pyrene was shown to
      proceed in oil-in-water emulsion systems. As a typical example, photoirradiation
      of pyrene in the presence of 1,4-dicyanobenzene and NaCN in a benzonitrile/water
      mixture (1/100, vol %) under vigorous stirring gave 1-cyanopyrene in a conversion
      yield of 83%, while an analogous reaction in an acetonitrile/water mixture (9/1,
      vol %) yielded this product in 61% yield. We evaluated the quantum yield of
      photocyanation in the oil-in-water emulsion system to be 0.17. Under optimum
      conditions, the quantum yield was improved to 0.68. Characteristics and possible
      mechanisms of the photocyanation reaction are discussed in detail.

PMID- 11950299
TI  - Influence of hydrogen bonding in the activation of nucleophiles: PhSH-(catalytic)
      KF in N-methyl-2-pyrrolidone as an efficient protocol for selective cleavage of
      alkyl/aryl esters and aryl alkyl ethers under nonhydrolytic and neutral
      conditions.
AB  - The nucleophilicity of arenethiols can be augmented via hydrogen bonding with
      "naked" halide anion. The activity of the halide anions follow the order F(-) >>
      Cl(-) approximately Br(-) approximately I(-) and is dependent on the
      countercation (Bu(4)N approximately Cs approximately K > Na >> Li). The solvent
      plays an important role in nucleophilic activation as well as regeneration of the
      effective nucleophile (e.g. ArS(-)) and those with high dielectric constant, high
      molecular polarizability, high donor number (DN), and low acceptor number (AN)
      are the most effective. Selective deprotection of alkyl/aryl esters and aryl
      alkyl ethers can be achieved under nonhydrolytic and neutral conditions by the
      treatment with thiophenol in 1-methyl-2-pyrrolidone (NMP) in the presence of a
      catalytic amount of KF. Aryl esters are selectively deprotected in the presence
      of alkyl esters and alkyl methyl ethers during intramolecular competitions.

PMID- 11950298
TI  - Substituent effects in the interconversion of phenylcarbene, bicyclo[4.1.0]hepta
      2,4,6-triene, and 1,2,4,6-cycloheptatetraene.
AB  - The effect of aryl substituents on the interconversion of phenylcarbene (PC),
      bicyclo[4.1.0]hepta-2,4,6-triene (BCT), and 1,2,4,6-cycloheptatetraene (CHTE) has
      been studied by density functional theory. It is found that substituents have a
      large effect on both the thermochemistry and activation energy of these
      rearrangements. For instance, para-substitution yields a range of overall
      activation energies for the formation of BCT from PC of 20.3 to 11.7 kcal/mol for
      the NH(2) and NO(2) substituents, respectively. In the syn-meta-substituted
      cases, all of the rearrangements to the substituted CHTE species are more
      exothermic than that of the parent PC. The proximity of the substituent to the
      carbene center can also affect the overall chemistry as in the case of ortho
      substituted species. Here, formation of bicyclic structures and ylides, which can
      then rearrange to stable structures, can compete with the ring-expansion process.
      Also, as calculated herein, the ortho substituents can, by a combination of
      mesomeric and steric interactions with the carbene center, affect the overall
      barrier to reversible ring expansion. Most notably, in the anti-ortho-substituted
      species, halogens (F and Cl) raise the activation barrier to ring expansion by
      approximately 5 kcal/mol. This is reminiscent of the effect of fluorine
      substitution on the chemistry (inter- and intramolecular) of phenylnitrene.

PMID- 11950300
TI  - Nucleophilic aromatic substitution for heteroatoms: an oxidative electrochemical
      approach.
AB  - The nucleophilic aromatic substitution for heteroatom through electrochemical
      oxidation of the intermediate sigma-complexes (Meisenheimer complexes) in simple
      nitroaromatic compounds is reported for the first time (NASX process). The
      studies have been carried out with hydride, cyanide, fluoride, methoxy, and
      ethanethiolate anions and n-butylamine as a nucleophile, at the cyclic
      voltammetry (CV) and preparative electrolysis level. The cyclic voltammetry
      experiments allow for detection and characterization of the sigma-complexes and
      they have led us to a proposal for the mechanism of the oxidation step.
      Furthermore, the power of the CV technique in the analysis of the reaction
      mixture throughout the whole chemical and electrochemical process is described.

PMID- 11950301
TI  - Diastereo- and enantioselective direct catalytic aldol reaction of 2
      hydroxyacetophenones with aldehydes promoted by a heteropolymetallic complex:
      catalytic asymmetric synthesis of anti-1,2-diols.
AB  - An anti-selective direct catalytic asymmetric aldol reaction of 2
      hydroxyacetophenones with aldehydes is described. The reaction is catalyzed by a
      heteropolymetallic complex to afford anti-alpha,beta-dihydroxy ketones as the
      major diastereomer with excellent enantioselectivity. The use of 2
      hydroxyacetophenones bearing electron-donating groups at the phenyl moiety
      enabled efficient transformation of the aldol products (alpha,beta-dihydroxy
      ketones) into the corresponding alpha,beta-dihydroxy ester derivatives via Baeyer
      Villiger oxidation. A plausible reaction mechanism is also discussed based on the
      stereochemistry of the products.

PMID- 11950302
TI  - Effects of solvents and water in Ti(III)-mediated radical cyclizations of
      epoxygermacrolides. Straightforward synthesis and absolute stereochemistry of (+)
      3alpha-hydroxyreynosin and related eudesmanolides.
AB  - The Cp(2)TiCl-mediated rearrangement of 1,10-epoxy-11beta,13-dihydrocostunolide
      (4) was carried out using different solvents and additives to develop an
      expeditious procedure for the synthesis of natural eudesmanolides via free
      radical chemistry. In the nonhalogenated solvents THF, benzene, and toluene the
      transannular cyclization, initiated by the homolytic opening of the oxirane ring,
      selectively led to the desired exocyclic alkene 5. When water was added to THF,
      however, the main product was reduced eudesmanolide 8. Experiments with D(2)O
      confirmed that the H-4 of 8 comes from water. To rationalize these results, a
      mechanistic hypothesis based on a water-solvated Cp(2)TiCl complex is proposed.
      Finally, the usefulness of Cp(2)TiCl for the synthesis of natural eudesmanolides
      has been proved using this reagent in the key step for the chemical preparation
      of (+)-3alpha-hydroxyreynosin (1) and (+)-reynosin (17). These syntheses
      confirmed the chemical structure of 1 and established the absolute
      stereochemistry of the natural products 1 and 17. The results obtained suggest
      that the combination of the biomimetic strategy employed, with Ti(III)-mediated
      free-radical chemistry, may come to represent a general method for the
      enantiospecific synthesis of more than 170 natural eudesmanolides containing an
      exocyclic double bond between C-4 and C-15.

PMID- 11950303
TI  - Reactions of silica chloride (SiO(2)Cl)/DMSO, a heterogeneous system for the
      facile regeneration of carbonyl compounds from thioacetals and ring-expansion
      annelation of cyclic thioacetals.
AB  - Silica chloride (SiO(2)Cl)/DMSO, as a heterogeneous system, has been efficiently
      used for deprotection of thioacetals into aldehydes in dry CH(2)Cl(2) at room
      temperature. Thioketals without enolizable hydrogens adjacent to a sulfur atom
      are converted easily to the corresponding ketones in high yields under similar
      reaction conditions. However, thioketals with enolizable methyl and methylene
      groups undergo ring-expansion reactions to afford 1,4-dithiepins and 1,4-dithiins
      in dry CH(2)Cl(2) at room temperature in good yields.

PMID- 11950304
TI  - Fluoronucleosides, isothiocyanato C-nucleosides, and thioureylene di-C
      nucleosides via cyclic sulfates.
AB  - Cyclic sulfates of N- and C-nucleosides (D-ribo and D-erythro configurations,
      respectively) are used to prepare 3'-fluoro and 3'-azido D-xylo N-nucleosides and
      L-threo C-nucleosides. The reduction of the 3'-azido C-nucleosides (furan,
      imidazoline-2-thione, and pyrrole derivatives) gives 3'-amino C-nucleosides,
      which, by reaction with thiocarbonyldiimidazole, are transformed into 3'
      isothiocyanato C-nucleosides. Reaction of the 3'-amino with the 3'-isothiocyanato
      C-nucleosides gives thioureylene di-C-nucleosides, a type of nucleotide analogue
      with a nonionic bridge isosteric of the phosphate group.

PMID- 11950305
TI  - The effect of substitutents on the strain energies of small ring compounds.
AB  - The effect of substitutents on the strain energy (SE) of cyclic molecules is
      examined at the CBS, G2, and G2(MP2) levels of theory. Alkyl substitutents have a
      meaningful effect upon the SE of small ring compounds. gem-Dimethyl substitution
      lowers the strain energy of cyclopropanes, cyclobutanes, epoxides, and
      dimethyldioxirane (DMDO) by 6-10 kcal/mol relative to an unbranched acyclic
      reference molecule. The choice of the reference compound is especially important
      for geminal electronegative substitutents. The SE of 1,1-difluorocyclopropane is
      estimated to be 20.5 kcal/mol relative to acyclic reference molecule 1,3
      difluoropropane but is 40.7 kcal/mol with respect to the thermodynamically more
      stable (DeltaE = -20.2 kcal/mol) isomeric reference compound 2,2-difluoropropane.
      The SE of dioxirane (DO) is estimated to be approximately 18 kcal/mol while the
      SE of DMDO is predicted to be approximately equal to 11 kcal/mol by using
      homodesmotic reactions that maintain a balanced group equivalency. The total
      energy (CBS-APNO) of DMDO is 2.6 kcal/mol lower than that of isomeric 1,2
      dioxacyclopentane that has an estimated SE of 5 kcal/mol. The thermodynamic
      stability of DMDO is a consequence of its relatively strong C-H (BDE = 102.7
      kcal/mol) and C-CH(3) (BDE = 98.9 kcal/mol) bonds. By comparison, the calculated
      sec-C-H and -C-CH(3) G2 bond dissociation energies in propane are 100.3 and 90.5
      kcal/mol.

PMID- 11950306
TI  - Synthesis of new trans double-bond sphingolipid analogues: Delta(4,6) and
      Delta(6) ceramides.
AB  - Unsaturation was introduced at Delta(4,6) and Delta(6) of the sphingoid chain of
      naturally occurring ceramide 1 via a beta-keto sulfoxide (12) and sulfone (18)
      derived from N-Boc-L-serine methyl ester acetonide (9), affording two novel
      ceramide analogues, (2S,3R)-2-octanoylamidooctadeca-(4E,6E)-diene-1,3-diol (2)
      and (2S,3R)-2-octanoylamidooctadec-(6E)-ene-1,3-diol (3). After C-alkylation of
      12 with (E)-1-bromo-2-tetradecene (8), a trans double bond was installed by
      elimination of PhS(O)H, providing conjugated dienone oxazolidine 13. Reaction of
      18 with 8, followed by desulfonation (Al(Hg)), afforded keto-oxazolidine 20,
      which bears a (E)-Delta(6) double bond. The syntheses of analogues 2 and 3 from
      ketones 13 and 20, respectively, were completed by the following sequence of
      reactions: diastereoselective reduction (NaBH(4)/CeCl(3) or DIBAL-H), hydrolysis
      of the oxazolidine ring, liberation of the amino group, and installation of the N
      amide group.

PMID- 11950307
TI  - EPR investigation of persistent radicals produced from the photolysis of dibenzyl
      ketones adsorbed on ZSM-5 zeolites.
AB  - Photolysis of ketones (1, 1-oMe, 2, 2-oMe, 3, and 4) adsorbed on ZSM-5 zeolites
      produces persistent carbon-centered radicals that can be readily observed by
      conventional steady-state EPR spectroscopy. The radicals are persistent for time
      periods of seconds to many hours depending on the supramolecular structure of the
      initial radical@zeolite complex and the diffusion and reaction dynamics of
      radicals produced by photolysis. The structures of the persistent radicals
      responsible for the observed EPR spectra are determined by a combination of
      alternate methods of generation of the same radical, by deuterium substitution,
      and by spectral simulation. A clear requirement for persistence is that the
      radicals produced by photolysis must either separate and diffuse from the
      external to the internal surface or be generated within the internal surface and
      separate and diffuse apart. The persistence of radicals located on the internal
      surface is the result of inhibition of radical-radical reactions. Radicals that
      are produced on the external surface and whose molecular structure prevents
      diffusion into the internal surface are transient because radical-radical
      reactions occur rapidly on the external surface. The reactions of the persistent
      radicals with oxygen and nitric oxide were directly studied in situ by EPR
      analysis. In the case of reaction with oxygen, persistent peroxy radicals are
      formed in high yield. The addition of nitric oxide scavenges persistent radicals
      and leads initially to a diamagnetic nitroso compound, which is transformed into
      a persistent nitroxide radical by further photolysis. The influence of variation
      of radical structure on transience/persistence is discussed and correlated with
      supramolecular structure and reactivity of the radicals and their parent ketones.

PMID- 11950309
TI  - Spectral properties and reactivity of diarylmethanol radical cations in aqueous
      solution. Evidence for intramolecular charge resonance.
AB  - Spectral properties and reactivities of ring-methoxylated diarylmethane and
      diarylmethanol radical cations, generated in aqueous solution by pulse and gamma
      radiolysis and by the one-electron chemical oxidant potassium 12
      tungstocobalt(III)ate, have been studied. The radical cations display three bands
      in the UV, visible, and vis-NIR regions of the spectrum. The vis-NIR band is
      assigned to an intramolecular charge resonance interaction (CR) between the
      neutral donor and charged acceptor rings, as indicated by the observation that
      the relative intensity of the vis-NIR band compared to that of the UV and visible
      bands does not increase with increasing substrate concentration and that the
      position and intensity of this band is influenced by the ring-substitution
      pattern. In acidic solution (pH = 4), monomethoxylated diarylmethanol radical
      cations 1a.(+ -)1e.(+) decay by C(alpha)-H deprotonation [k = (1.7-1.9) x 10(4)s(
      1)] through the intermediacy of a ketyl radical, which is further oxidized in the
      reaction medium to give the corresponding benzophenones, as evidenced by both
      time-resolved spectroscopic and product studies. With the dimethoxylated radical
      cation 2.(+), C(alpha)-H deprotonation is instead significantly slower (k = 6.7 x
      10(2)s(-1)). In basic solution, 1a.(+)-1e.(+) undergo (-)OH-induced deprotonation
      from the alpha-OH group with k(OH.)approximately equal to 1.4 x 10(10)M(-1)s(-1),
      leading to a ketyl radical anion, which is oxidized in the reaction medium to the
      corresponding benzophenone.

PMID- 11950308
TI  - Chemistry of stable iminopropadienones, RN=C=C=C=O.
AB  - The synthesis, spectroscopic properties, and chemical reactions of the stable
      (neopentylimino)-, (mesitylimino)-, and (o-tert-butylphenylimino)propadienones
      (6) are reported. Nucleophilic addition of amines affords the malonic
      amidoamidines 7 and 8. 3,5-Dimethylpyrazole reacts analogously to form 9b.
      Addition of 1,2-dimethylhydrazine produces pyrazolinones 10-12. Addition of N,N'
      dimethyldiaminoethane, -propane, and -butane gives diazepine, diazocine, and
      diazonine derivatives 13-15, respectively (X-ray structures of 13c, 14a, and 15a
      are available). The mesoionic pyridopyrimidinium olates 18 are obtained by
      addition of 2-(methylamino)pyridine (X-ray structure of 18b available). Primary 2
      aminopyridines afford the pyridopyrimidininones 20-29 and 31 (X-ray structure of
      21a available), and 2-aminopyrimidines and 2-aminopyrazine afford
      pyrimidopyrimidinones and pyrazinopyrimidinones 33-35. Pyrimidoisoquinolinone 36
      results from 1-aminoisoquinoline and pyridoquinolinone 40 from 8-aminoquinoline.
      2-Aminothiazoline and 2-aminothiazole afford thiazolopyrimidinone derivatives 41
      43 (X-ray structure of 43a available).

PMID- 11950311
TI  - Metal-catalyzed hydrosilylation of alkenes and alkynes using
      dimethyl(pyridyl)silane.
AB  - Metal-catalyzed hydrosilylation of alkenes and alkynes using
      dimethyl(pyridyl)silane is described. The hydrosilylation of alkenes using
      dimethyl(2-pyridyl)silane (2-PyMe(2)SiH) proceeded well in the presence of a
      catalytic amount of RhCl(PPh(3))(3) with virtually complete regioselectivity. By
      taking advantage of the phase tag property of the 2-PyMe(2)Si group,
      hydrosilylation products were isolated in greater than 95% purity by simple acid
      base extraction. Strategic catalyst recovery was also demonstrated. The
      hydrosilylation of alkynes using 2-PyMe(2)SiH proceeded with a
      Pt(CH(2)=CHSiMe(2))(2)O/P(t-Bu)(3) catalyst to give alkenyldimethyl(2
      pyridyl)silanes in good yield with high regioselectivity. A reactivity comparison
      of 2-PyMe(2)SiH with other related hydrosilanes (3-PyMe(2)SiH, 4-PyMe(2)SiH, and
      PhMe(2)SiH) was also performed. In the rhodium-catalyzed reaction, the reactivity
      order of hydrosilane was 2-PyMe(2)SiH >> 3-PyMe(2)SiH, 4-PyMe(2)SiH, PhMe(2)SiH,
      indicating a huge rate acceleration with 2-PyMe(2)SiH. In the platinum-catalyzed
      reaction, the reactivity order of hydrosilane was PhMe(2)SiH, 3-PyMe(2)SiH >> 4
      PyMe(2)SiH > 2-PyMe(2)SiH, indicating a rate deceleration with 2-PyMe(2)SiH and 4
      PyMe(2)SiH. It seems that these reactivity differences stem primarily from the
      governance of two different mechanisms (Chalk-Harrod and modified Chalk-Harrod
      mechanisms). From the observed reactivity order, coordination and electronic
      effects of dimethyl(pyridyl)silanes have been implicated.

PMID- 11950312
TI  - Synthesis of phthalides and 3,4-dihydroisocoumarins using the palladium-catalyzed
      intramolecular benzannulation strategy.
AB  - A novel method for the synthesis of phthalides and 3,4-dihydroisocoumarins via
      the palladium-catalyzed intramolecular benzannulation of bis-enyne and enyne
      diyne systems is described. Various kinds of substituted phthalides 9 and 17 and
      3,4-dihydroisocoumarins 19 were synthesized from 8, 16, and 18, respectively, in
      moderate to excellent yields. The benzannulation reaction proceeded
      chemoselectively to give the corresponding fused ring compounds A without the
      formation of the regioisomeric products B (eq 6). Furthermore, this methodology
      was applied to the synthesis of biologically active 3-n-butylphthalide 23.

PMID- 11950310
TI  - Complexation in pseudorotaxanes based on alpha-cyclodextrin and different
      alpha,omega-diaminoalkanes by NMR diffusion measurements.
AB  - The interactions of 1,4-diaminobutane (1), 1,6-diaminohexane (2), 1,8
      diaminooctane (3), 1,10-diaminodecane (4), and 1,12-diaminododecane (5) with
      alpha-cyclodextrin (alpha-CD) were studied in aqueous solutions by NMR diffusion
      measurements before and after protonation. The correlation between the
      association constant and the length of the alkyl chain of the diamine unit was
      studied. The assumption that protonation on the amino groups can be used as a
      stopper and, as a result, to convert the pseudorotaxanes into rotaxanes was
      tested. In addition, other factors that can affect the pseudorotaxane stability,
      such as the effects of temperature, were tested. On the basis of these
      measurements, the following conclusions could be reached: (1) The association
      constant increases with the increase in the alkyl chain length. (2) For the salts
      (2b-5b), both in neutral and in acidic solutions, the binding constants increase
      as the number of CH(2) units increases. (3) The association constants of the
      complexes of the diaminoalkane salts and alpha-CD are lower than those of the
      corresponding neutral diaminoalkanes. (4) This difference between the binding
      constants of the diaminoalkanes and their respective salts decreases as the chain
      length increases. (5) By examining the effects of temperature on the (1)H NMR
      spectra, it was found that after addition of DCl the energy barrier for the
      threading-dethreading process of the salt of 5a is larger than that for the salt
      of 4a.

PMID- 11950313
TI  - Conformational studies by dynamic NMR. 88.(1) stereomutation processes in the
      diastereoisomers of a representative amino alcohol and related amide precursors.
AB  - The barriers for three internal motions (i.e., phenyl and tert-butyl rotation as
      well as N-inversion) have been determined by dynamic NMR spectroscopy in the two
      diastereoisomeric forms of a typical amino alcohol [dimethylamino-2,4,4-trimethyl
      3-phenyl-3-pentanol, Me(2)NCH(2)CHMeC(OH)PhBu(t)]. The two structures were
      assigned by connection with those of the corresponding amide precursors
      determined by single-crystal X-ray diffraction. These amides (C=O in place of
      CH(2)) too were found to undertake internal motions amenable to NMR observation,
      i.e., phenyl, tert-butyl, and N-CO rotations: the corresponding barriers were
      also measured. Ab initio computations indicate that H-bonding makes all these
      molecules adopt six-membered cyclic conformations, a conclusion which agrees well
      with the X-ray crystal structure determined for the amide precursors.

PMID- 11950314
TI  - Asymmetric Diels-Alder, Michael, and aldol reactions using a planar chiral 1,3
      oxazol-2(3H)-one derived from (R)-(+)-4-hydroxy-[2.2]paracyclophane.
AB  - (+)-(R)-[2.2]Paracyclophane[4,5-d]-1,3-oxazol-2(3H)-one exhibiting planar
      chirality has been used as a chiral auxiliary in asymmetric Diels-Alder, Michael,
      and aldol reactions of alpha,beta-unsaturated carboxy and enolate imides,
      respectively. The endo-exo- and face-diastereoselectivity is good and is
      controlled by the spatial relationship between the prochiral center and the C9
      C10 ethylene bridge of the [2.2]paracyclophane moiety. The chiral auxiliary is
      easily removed and quantitatively recovered.

PMID- 11950315
TI  - Aerobic oxidation of N-alkylamides catalyzed by N-hydroxyphthalimide under mild
      conditions. Polar and enthalpic effects.
AB  - The oxidation of N-alkylamides by O(2), catalyzed by N-hydroxyphthalimide (NHPI)
      and Co(II) salt, leads under mild conditions to carbonyl derivatives (aldehydes,
      ketones, carboxylic acids, imides) whose distribution depends on the nature of
      the alkyl group and on the reaction conditions. Primary N-benzylamides lead to
      imides and aromatic aldehydes at room temperature without any appreciable amount
      of carboxylic acids, while under the same conditions nonbenzylic derivatives give
      carboxylic acids and imides with no trace of aldehydes, even at very low
      conversion. These results are explained through hydrogen abstraction by the
      phthalimide-N-oxyl (PINO) radical, whose reactivity with benzyl derivatives is
      governed by polar effects, so that benzylamides are much more reactive than the
      corresponding aldehydes. The enthalpic effect is, however, dominant with
      nonbenzylic amides, making the corresponding aldehydes much more reactive than
      the starting amides. The importance of the bond dissociation energy (BDE) of the
      O-H bond in NHPI is emphasized.

PMID- 11950316
TI  - Photochemical synthesis of aldehydes in the solid phase.
AB  - A substituted anthraquinone (AQ), previously shown to photochemically generate
      benzaldehyde in methanol solution, was attached to a commercially available resin
      via an 11 carbon tether and an amide bond. Photolysis of the polymer-bound AQ
      with visible or 350 nm UV light resulted in the formation of benzaldehyde in
      yields of 50-55% as determined by HPLC. The phenolic positions in the polymer
      were then alkylated using benzyl bromide and 1-iodo-3-(4-nitrophenyl)propane in a
      coupling reaction with K(2)CO(3) as a base and a solution-phase proton shuttle.
      Photolysis of these alkylated polymers resulted in the formation of benzaldehyde
      (54-89%) and 3-(4-nitrophenyl)-propanal (58-67%). The yields of both aldehydes
      dropped considerably with subsequent realkylation and photolysis, and the polymer
      beads began to show signs of deterioration. This is the first time that aldehydes
      have been made photochemically on a solid-supported phase.

PMID- 11950317
TI  - An enantioselective synthesis of tarchonanthuslactone.
AB  - An enantioselective synthesis of tarchonanthuslactone has been achieved in eight
      steps from ethyl sorbate. The asymmetry of the route was introduced via a
      Sharpless asymmetric dihydroxylation allowing access to either enantiomer. The
      synthesis utilizes a palladium-catalyzed reduction and a diastereoselective base
      catalyzed acetal formation as the key steps. The pyran ring of
      tarchonanthuslactone was established by a Still-olefination/lactonization
      sequence. DCC-mediated attachment of dihydrocaffeic acid completed the synthesis
      of tarchonanthuslactone in a 19% overall yield.

PMID- 11950318
TI  - A convenient synthesis of cis and trans 4-tert-butoxycarbonyl-substituted
      cyclohexylglycine.
AB  - A novel synthesis of cis and trans substituted 4-tert-butoxycarbonyl
      cyclohexylglycines via asymmetric aminohydroxylation of vinyl styrene followed by
      reduction of the aromatic ring and subsequent oxidation is reported.

PMID- 11950319
TI  - Unusual regioselection in the Mitsunobu reactions of syn-2,3-dihydroxy esters:
      synthesis of statine and its diastereomer.
AB  - Mitsunobu reactions of syn-2,3-dihydroxy esters exhibit a complete regioselection
      for the beta-hydroxyl group. Benzoylation, azidation, and tosylation have been
      performed under these conditions. Beta-functionalizations of syn-2,3-dihydroxy
      esters are uncommon, and the Mitsunobu reactions are complementary to other diol
      chemistries in the regioselection. In addition, the configurational inversion
      accompanying the Mitsunobu protocol offers a means for diastereochemical
      diversity, as exemplified by a synthesis of statine and its anti diastereomer.
      These findings will further expand the synthetic utilities of the Sharpless AD
      process.

PMID- 11950320
TI  - Diastereoselective synthesis of S-tert-butyl-beta-(trifluoromethyl)isocysteine.
AB  - Both diastereoisomers of S-tert-butyl-beta-(trifluoromethyl)isocysteine have been
      synthesized stereoselectively by the sequential reactions of trifluoroacetimidoyl
      chloride with the lithium enolate of tert-butyl alpha-tert-butylthioacetate,
      followed by the diastereoselective reduction of the imino group with sodium
      borohydride in the presence of zinc(II) or di(ethylene glycol) dimethyl ether,
      and finally by the deprotection of N-aryl and tert-butyl ester groups.

PMID- 11950321
TI  - Selective binding of two-armed diketopiperazine receptors to side-chain-protected
      peptides.
AB  - The binding properties of two-armed receptors based on a diketopiperazine
      template toward side-chain-protected peptides have been elucidated. Selective
      binding of these diketopiperazine receptors is not limited to side-chain-free
      peptides, but combinatorial on-bead assays show that also side-chain-protected
      peptides are recognized with high specificity. Furthermore, the screening of
      several dye-marked diketopiperazine receptors against an encoded side-chain
      protected tripeptide library demonstrated not only their high binding
      specificities but also revealed that small structural changes suffice to alter
      the binding preferences significantly.

PMID- 11950322
TI  - Synthesis and chemistry of 4,5-dimagnesioimidazole dianions.
AB  - An experimentally convenient procedure for the generation of 4,5
      dimagnesioimidazoles is described. N-Protected 2-substituted 4,5-diiodoimidazoles
      were treated with i-PrMgCl (2.4 equiv) in THF at 0-5 degrees C. The resulting
      vicinal dianions reacted with electrophiles to give 4,5-disubstituted imidazoles
      in 27-71% yields.

PMID- 11950323
TI  - Tertiary pentyl groups enhance salen titanium catalyst for highly
      enantioselective trimethylsilylcyanation of aldehydes.
AB  - tert-Pentyl groups are recognized to be highly effective steric groups that can
      enhance enantioselectivity of salen titanium complexes when they are used in
      asymmetrical cyanation of aromatic aldehydes. High ee (92-97%) has been obtained
      with several aldehyde substrates. Compared to its tert-butyl analogue, the tert
      pentyl group has been found to improve enantioselectivity and in some cases quite
      dramatically.

PMID- 11950324
TI  - Regioselective synthesis of 3-alkylindoles mediated by zinc triflate.
AB  - Zinc triflate was found to be an effective reagent for the C3-alkylation of
      indoles by alkyl halides in the presence of Hunig's base and tetrabutylammonium
      iodide. This new method for indole alkylation proceeds by a S(N)1-like pathway,
      and is general for allylic, benzylic, and tertiary halides.

PMID- 11950325
TI  - Electronic effects on O-H proton dissociation energies of phenolic cation
      radicals: a DFT study.
AB  - The electronic effects on O-H proton dissociation energies (PDEs) of para- and
      meta-substituted phenolic cation radicals have been investigated by density
      functional theory (DFT) using B3LYP function on a 6-31G(d, p) basis set. The
      calculation results indicate that electron-donating groups raise the O-H PDE and
      electron-withdrawing groups reduce the parameter, which are opposite to the
      electronic effects on O-H bond dissociation energies (BDEs). In addition, the
      electronic effects on O-H PDE are much stronger than those on O-H BDE. The
      differences result from the distinct electronic effects on stabilities of
      phenolic cation radicals and parent phenols. The finding also implies the proton
      transfer process is unlikely a rate-controlling step for phenolic antioxidants to
      scavenge free radicals. Moreover, like O-H BDE, O-H PDE correlate better with the
      resonance parameter R+ than with field/inductive parameter F. Therefore, O-H PDEs
      of para-substituted phenolic cation radicals are mainly governed by the resonance
      effect.

PMID- 11950326
TI  - Synthesis and spectroscopic properties of a new class of strongly fluorescent
      dipyrrinones.
AB  - A new, highly fluorescent (Phi(F) > or = 0.8) chromophore has been synthesized in
      one step from dipyrrinones by reaction with N,N-carbonyldiimidazole to form the
      3H,5H-dipyrrolo[1,2-c:2',1'-f]pyrimidine-3,5-dione nucleus.

PMID- 11950327
TI  - A biomimetic approach to the synthesis of an antiviral marine steroidal
      orthoester.
AB  - Orthoesterol B, a marine natural product exhibiting antiviral activities,
      contains a [3.2.1]-bicyclic orthobutyrate bridging the steroid side chain and
      ring D. A biosynthetic reaction was proposed by which rearrangement of an epoxy
      ester results in the formation of the orthoester moiety. Steroidal model
      compounds incorporating 16-butyroxy and 20,22-epoxy groups were synthesized from
      tigogenin and were shown to rearrange to orthoesters under mild acidic catalysis.

PMID- 11950328
TI  - Pd/C as a reusable catalyst for the coupling reaction of halophenols and
      arylboronic acids in aqueous media.
AB  - Pd/C was found to catalyze the Suzuki-Miyaura coupling reaction of halophenols in
      aqueous media. When halophenols were treated with ArB(OH)(2) and a catalytic
      amount of 10% Pd/C (0.3 mol % Pd) in aqueous K(2)CO(3) solution, the
      corresponding hydroxybiaryls were obtained in a high yield or quantitatively. The
      palladium catalyst was easily recovered and reused.

PMID- 11950329
TI  - A strategy for the construction of caged diols using a photolabile protecting
      group.
AB  - Caged analogues of biologically active compounds have received widespread
      attention as temporally and spatially controlled probes of cell-based processes.
      Recently, a coumarin-4-ylmethyl derivative has been used to cage carboxylates,
      sulfonates, carbamates, and phosphates. We describe herein a synthetic strategy
      that furnishes photosensitive caged diols and provides an entry into the
      protection/photodeprotection of functionality with modest leaving group
      abilities.

PMID- 11950330
TI  - A high-throughput screening protocol for fast evaluation of enantioselective
      catalysts.
AB  - A new high-throughput screening protocol that allows fast evaluation of
      enantioselective catalysts has been developed. The usefulness of norephedrine
      derived beta-amino alcohols as catalysts for the enantioselective alkylation of
      prochiral aldehydes has been determined by simultaneous screening of three
      representative substrates. GC analysis of the crude product mixture using a
      selectively modified cyclodextrin as the chiral stationary phase avoids time
      consuming workup procedures. The chemical yield, enantioselectivity, substrate
      specificity, and catalytic activity of the chiral catalysts as well as the
      induced absolute configuration have been determined in a single screening
      experiment and two short GC runs.

PMID- 11950331
TI  - Syntheses of novel 4-tert-alkyl ether proline-based 16- and 17-membered
      macrocyclic compounds.
AB  - Starting from N-Cbz-4-hydroxyproline methyl ester 1, a boron trifluoride-diethyl
      etherate-catalyzed reaction provided 4-tert-alkyl ether proline 4. Two
      deprotections and amide bond formations furnished the phenol alcohol 2. The
      macrocyclization of 2 was accomplished through a Mitsunobu reaction using
      triphenylphosphine and 1,1'-(azodicarbonyl)dipiperidine (ADDP), to afford novel
      16- and 17-membered proline-based macrocyclic compounds of type 3.

PMID- 11950333
TI  - Synthesis of phosphole-2,5-dicarboxylic acids via a [1,5]-shift of carbon dioxide
      around the phosphole nucleus.
AB  - A new methodology for the synthesis of 1-P-functionalized phosphole-2,5
      dicarboxylic acids is described. The carboxylic group is introduced through a two
      step sequence which involves a preliminary attack of the phospholide unit onto
      CO(2) followed by a [1,5]-shift reaction of the CO(2)Li group around the
      phosphole nucleus. This approach was extended to the preparation of a new type of
      bidentate ligands. [reaction: see text]

PMID- 11950334
TI  - 9-BBN: An amino acid protecting group for functionalization of amino acid side
      chains in organic solvents.
AB  - 9-Borabicyclononane (9-BBN) has been utilized to protect functionalized amino
      acids for potential chemoselective side chain manipulation. The 9-BBN group
      imparts organic solubility to otherwise hydrophilic molecules and is tolerant of
      a wide range of reaction conditions. The high degree of solubility of these
      molecules in THF is particularly noteworthy. It is cleaved with either aqueous
      HCl or by exchange with ethylenediamine in methanol. [reaction: see text]

PMID- 11950335
TI  - Di-[1,10]-phenanthrolinyl diazines: a new family of bis-tridentate chelators.
AB  - A series of three bis-tridentate bridging ligands has been prepared in which two
      1,10-phenanthroline units have been symmetrically appended to a central
      pyridazine, pyrimidine, or pyrazine ring. These ligands have been treated with
      [Ru(tpy-d(11))Cl(3)] to afford both mono- and bimetallic complexes that show very
      self-consistent NMR properties. [structure: see text]

PMID- 11950336
TI  - On a novel chromanone-naphthalenetrione rearrangement related to vitamin E.
AB  - 4-Oxo-alpha-tocopherol (7) was synthesized in an efficient three-step procedure
      starting from alpha-tocopheryl acetate (1b) and rearranged under physiological
      conditions into naphthalenetrione 4, a minor vitamin E metabolite. The
      rearrangement involves a [4 + 2]-cycloaddition as the key step. [reaction: see
      text]

PMID- 11950337
TI  - The rearrangement route to 3-CH(2)X-2-azabicyclo[2.1.1]hexanes. Substituent
      control of neighboring group participation.
AB  - The stereocontrolled synthesis of a functionalized 3-hydroxymethyl-2
      azabicyclo[2.1.1]hexane synthon for a variety of methano-bridged pyrrolidines has
      been effected. The key step in an electrophilic addition-rearrangement route uses
      a 3-nosyloxymethyl group in the 2-azabicyclo[2.2.0]hex-5-ene precursor in order
      to suppress unwanted competitive oxygen neighboring group participation.
      [reaction: see text]

PMID- 11950338
TI  - Enantioselective monoreduction of 2-alkyl-1,3-diketones mediated by chiral
      ruthenium catalysts. dynamic kinetic resolution.
AB  - The reduction of 2-alkyl-1,3-diketones using (R,R)- or (S,S)-RuCl[N-(tosyl)-1,2
      diphenylethylenediamine](p-cymene) in the presence of formic acid and
      triethylamine affords syn-2-alkyl-3-hydroxy ketones as the major products with
      high enantioselectivity. [reaction: see text]

PMID- 11950339
TI  - Synthesis and NKT cell stimulating properties of fluorophore- and biotin-appended
      6"-amino-6"-deoxy-galactosylceramides.
AB  - Alpha-galactosylceramides are potent stimulators of human T cells. Stimulation
      occurs through binding of the glycolipids by CD1d, presentation to T cells, and
      formation of a CD1d-glycolipid-T cell receptor complex. To facilitate the
      elucidation of the structural features of glycolipids necessary for T cell
      stimulation, alpha-galactosylceramides have been prepared with small molecules
      appended at the C6 position of the sugar. The appended molecules do not
      significantly influence the abilities of the glycolipids to stimulate T cells.
      [reaction: see text]

PMID- 11950340
TI  - Formation of bicyclic ethers from Lewis acid promoted cyclizations of cyclic
      oxonium ions.
AB  - Oxacycles carrying a vinyl group and an acetal were extended with a cyclization
      terminator (vinyl silane or vinyl sulfide) by Suzuki coupling. Treatment with
      Lewis acid induced cyclization to provide bicyclic ethers in reasonable yields.
      In the case of the vinyl silane, an ene-like mechanism is preferred, whereas the
      thioenol ether enters into a Prins-type reaction channel. In one instance, the
      bicyclic compound was opened to give the ten-membered functionalized enone 24.
      [reaction: see text]

PMID- 11950341
TI  - A new synthesis of butadienyl- and styrylboronic esters: highly reactive
      intermediates for Suzuki cross-coupling.
AB  - Alkoxy-functionalized butadienyl- and styrylboronic esters have been synthesized
      starting from alpha,beta-unsaturated acetals. These derivatives readily cross
      couple with aryl substrates, and the obtained products can be transformed under
      mild conditions into aromatic ketones, achieving the same result as an acylation
      reaction. [reaction: see text]

PMID- 11950343
TI  - 2,6-diaminopurine in TNA: effect on duplex stabilities and on the efficiency of
      template-controlled ligations.
AB  - Replacement of adenine by 2,6-diaminopurine-two nucleobases to be considered
      equivalent from an etiological point of view-strongly enhances the stability of
      TNA/TNA, TNA/RNA, or TNA/DNA duplexes and efficiently accelerates template
      directed ligation of TNA ligands. [reaction: see text]

PMID- 11950342
TI  - Base-pairing systems related to TNA: alpha-threofuranosyl oligonucleotides
      containing phosphoramidate linkages.
AB  - (3'NH)- and (2'NH)-TNA, two isomeric phosphoramidate analogues of TNA (alpha
      threofuranosyl-(3'-->2') oligonucleotides), are shown to be efficient Watson
      Crick base-pairing systems and to undergo intersystem cross-pairing with TNA,
      RNA, and DNA. [reaction: see text]

PMID- 11950344
TI  - Synthesis of disubstituted cucurbit[6]uril and its rotaxane derivative.
AB  - Synthesis of diphenyl cucurbit[6]uril (CB[6]) has been achieved via co
      oligomerization of diphenyl glycoluril and unsubstituted glycoluril. The
      unsymmetrically substituted CB[6], Ph(2)CB[6], was further converted to a
      rotaxane incorporating bis(dinitrophenyl)spermine. [reaction: see text]

PMID- 11950345
TI  - Synthesis of side chain truncated 3"-aldehyde, 3"-carboxylic acid, and 1"
      aldehyde from nodulisporic acid A.
AB  - An efficient synthesis of the truncated 3"-aldehyde (3) from nodulisporic acid A
      (1) under mild conditions is described. Further oxidation of 3 to 3"-carboxylic
      acid (4) and its subsequent oxidative degradation produced 1"-aldehyde (5). These
      new derivatives are versatile intermediates for the preparation of new, side
      chain modified derivatives of nodulisporic acid A. [reaction: see text]

PMID- 11950346
TI  - A convenient synthesis of C-22 and C-25 stereoisomers of cephalostatin north 1
      side chain from spirostan sapogenins.
AB  - A simple transformation of the eight-carbon side chain of a natural spirostan
      sapogenin into the cephalostatin north 1 spiroketal moiety is described. This
      methodology, based on an intramolecular hydrogen abstraction reaction promoted by
      alkoxy radicals, permits the synthesis of C-22 and C-25 stereoisomers of the
      dioxaspiro[4.4]nonane cephalostatin ring system. The acid-catalyzed isomerization
      of the spirocenter in the different isomers is studied. [reaction: see text]

PMID- 11950347
TI  - Stereoselective synthesis of functionalized gamma-amino esters: azetidinium salts
      and epoxy esters.
AB  - Addition of several lithium ester enolates to chiral 1-aminoalkyl chloromethyl
      ketones 1 affords enantiomerically pure 3-hydroxyazetidinium salts 3 or 3-(1'
      aminoalkyl)-3,4-epoxy esters 4, depending on the reaction conditions. [reaction:
      see text]

PMID- 11950348
TI  - Synthesis of different chiral amino gamma-butyrolactones and amino gamma
      butenolides.
AB  - Different transformations of chiral epoxy esters 1 afford two different amino
      gamma-butyrolactones 2 and 6, and amino gamma-butenolides 8, by different
      nucleophilic opening-closing processes. [reaction: see text]

PMID- 11950349
TI  - Total synthesis of hectochlorin.
AB  - Hectochlorin (1) is a marine natural product with significant fungicidal
      activity. A synthesis effort was initiated to develop a flexible route to
      hectochlorin which would allow access to analogues with potentially improved
      activity and/or attributes relative to the natural product. A successful total
      synthesis of hectochlorin is described. [structure: see text]

PMID- 11950350
TI  - Rhodium-catalyzed asymmetric ring opening of oxabicyclic alkenes with
      organoboronic acids.
AB  - The first rhodium(I)-catalyzed asymmetric addition of organoboronic acids to
      oxabicyclic alkenes is reported. This asymmetric ring-opening (ARO) reaction can
      proceed in high yield under very mild conditions with electronically diverse
      organoboronic acids, in a highly diastereoselective and enantioselective manner.
      [structure: see text]

PMID- 11950351
TI  - A facile one-carbon homologation of aryl aldehydes to amides.
AB  - The easily accessible 2-aryl-1,1-dibromo-1-alkenes can be converted to amides
      under unusually mild conditions in good to excellent yields. Both electron
      donating and electron-withdrawing substitutions on the aromatic rings are
      tolerated, and the reaction works well with hindered alkylamines. This simple
      homologation could find broad applications. [reaction: see text]

PMID- 11950352
TI  - Transition metal salts-catalyzed aza-Michael reactions of enones with carbamates.
AB  - Several transition metal salts were found to catalyze aza-Michael reactions of
      enones with carbamates efficiently. The catalytic activity was strongly dependent
      on the nature of the metal salts. While conventional Lewis acids such as
      BF(3).OEt(2), AlCl(3), or TiCl(4) showed lower activity, group 7-11 transition
      metal salts in higher oxidation states such as ReCl(5), Fe(ClO(4))(3).9H(2)O,
      RuCl(3).nH(2)O, OsCl(3).3H(2)O, RhCl(3).nH(2)O, PtCl(4).5H(2)O, or AuCl(3).H(2)O
      exhibited higher catalytic activity. [reaction: see text]

PMID- 11950353
TI  - A nitric oxide-releasing polydiazeniumdiolate derived from acetonitrile.
AB  - Acetonitrile, frequently used as a solvent in reactions of nitric oxide (NO) with
      amines and other nucleophiles to introduce the [N(O)NO](-) (diazeniumdiolate)
      functional group, has itself been shown to react with NO in the presence of
      strong base to yield methane trisdiazeniumdiolate (1), presumably via an
      intermediate trisdiazeniumdiolated imidate. Aqueous hydrolysis of 1 does not
      follow simple first-order kinetics and produces mixtures of NO and nitrous oxide
      in ratios that vary with solution pH. [reaction: see text]

PMID- 11950354
TI  - A pyrrolo-tetrathiafulvalene belt and its TCNQ complex: syntheses and X-ray
      crystal structures.
AB  - A general and efficient four-step synthesis of a tetrathiafulvalene-belt 6,
      starting from the monopyrrolo-tetrathiafulvalene building block 1, is described,
      together with its 7,7,8,8-tetracyano-p-quinodimethane charge transfer complex.
      The complexation of the electron acceptor 7,7,8,8-tetracyano-p-quinodimethane by
      the tetrathiafulvalene-belt 6 was investigated both in solution and in the solid
      state. [reaction: see text]

PMID- 11950355
TI  - Stereoselective Michael-aldol tandem reaction of phenylselenomagnesium bromide
      with acetylenic sulfones and aldehydes. An efficient synthesis of
      polyfunctionalized allylic alcohols.
AB  - A mixture of phenylselenomagnesium bromide, an acetylenic sulfone, and an
      aldehyde in THF/CH(2)Cl(2) afforded Michael-aldol tandem adduct, i.e., (Z)-beta
      phenylseleno-alpha-(p-tolylsulfonyl)allylic alcohol, in good yield with high
      stereoselectivity. The stereoselectivity greatly depended on solvent. [reaction:
      see text]

PMID- 11950356
TI  - Biomimetic stereoselective formation of methyllanthionine.
AB  - Fmoc-(2R,3S)-3-methyl-Se-phenylselenocysteine was used for the synthesis of
      dehydrobutyrine (Dhb)-containing peptides. Biomimetic cyclization via Michael
      addition of Cys to a Dhb yielded the B-ring of the lantibiotic subtilin as a
      single diastereomer. The methyllanthionine product was shown to have the natural
      configuration by preparation of the authentic stereoisomer. The formation of a
      single isomer suggests that the prepeptide has a strong intrinsic preference for
      the stereochemistry observed in lantibiotics. [reaction: see text]

PMID- 11950357
TI  - A novel palladium-catalyzed synthesis of 1,2-dihydroquinoxalines and 3,4
      dihydroquinoxalinones.
AB  - Reactions of enamines, derived from 2-nitroanilines and alpha-substituted
      aldehydes, with carbon monoxide (6 atm) in the presence of a catalytic amount of
      bis(dibenzylideneacetone)palladium(0) (Pd(dba)(2)) and 1,3
      bis(diphenylphosphino)propane (dppp) afford readily separated mixtures of 1,2
      dihydroquinoxalines and 3,4-dihydroquinoxalinones. Addition of a catalytic amount
      of 1,10-phenanthroline to the reaction mixture substantially improved the yield
      of products. [reaction: see text]

PMID- 11950358
TI  - Stereocontrolled total synthesis of pancratistatin.
AB  - A new total synthesis of the antitumor alkaloids, pancratistatin (1), has been
      accomplished from readily available staring materials. The Claisen rearrangement
      of dihydropyranethylene 5 was employed to construct the A and C rings. Stereo-
      and regiocontrolled functional group interchange, such as iodolactonization,
      dihydroxylations, and a cyclic sulfate elimination reaction, allows for the
      production of the target natural product. [reaction: see text]

PMID- 11950359
TI  - Magnesium bromide mediated highly diastereoselective heterogeneous hydrogenation
      of olefins.
AB  - Palladium on carbon combined with magnesium bromide catalyzed hydrogenation of
      Baylis-Hillman olefins to afford the corresponding aldol derivatives in a highly
      syn-diastereoselective manner is described. [reaction: see text]

PMID- 11950360
TI  - Efficient NMR enantiodifferentiation of chiral quats with BINPHAT anion.
AB  - Hexacoordinated phosphorus BINPHAT anion is an efficient NMR chiral shift agent
      for quaternary ammonium cations (quats) leading to large separations
      (DeltaDeltadelta up to 0.29 ppm) of the proton signals of the enantiomers.
      [reaction: see text]

PMID- 11950362
TI  - Stereoselective synthesis of myo-inositol via ring-closing metathesis: a building
      block for glycosylphosphatidylinositol (GPI) anchor synthesis.
AB  - Here we report a concise stereoselective synthesis of myo-inositol via ring
      closing metathesis. A readily available bis-Weinreb amide of D-tartrate served as
      a key intermediate. [reaction: see text]

PMID- 11950361
TI  - 12-Acylindolo[1,2-c]quinazolines by palladium-catalyzed cyclocarbonylation of o
      alkynyltrifluoroacetanilides.
AB  - 6-Trifluoromethyl-12-acylindolo[1,2-c]quinazolines are prepared in high yield
      through the palladium-catalyzed reaction of bis(o
      trifluoroacetamidophenyl)acetylene with aryl or vinyl halides and triflates. The
      reaction, which tolerates a variety of important functional groups, probably
      involves the formation of a 3-acyl-2-(o-trifluoroacetamidophenyl)indole
      intermediate, followed by its cyclization to the indoloquinazoline product.
      [reaction: see text]

PMID- 11950363
TI  - Regiocontrolled synthesis of substituted thiazoles.
AB  - The regiocontrolled synthesis of 2,5-disubstituted and 2,4,5-trisubstituted
      thiazoles from ethyl 2-bromo-5-chloro-4-thiazolecarboxylate 1 using sequential
      palladium-catalyzed coupling reactions is described. [reaction: see text]

PMID- 11950365
TI  - Highly diastereoselective synthesis of decalin skeletons with quaternary carbon
      centers via the tandem oxy-Cope/ene/Claisen reaction.
AB  - The highly diastereoselective cascade sequence of three successive thermal
      pericyclic reactions of 1,2-divinylcyclohexanol allyl and propargyl ethers is
      described. This novel tandem process provides an efficient synthesis of sesqui-
      and diterpenoid skeletons having a quaternary carbon at C9. [reaction: see text]

PMID- 11950364
TI  - trans-6-Aminocyclohept-3-enols, a new designed polyfunctionalized chiral building
      block for the asymmetric synthesis of 2-substituted-4-hydroxypiperidines.
AB  - trans-6-Aminocyclohept-3-enols 18 and ent-18 are new designed polyfunctionalized
      chiral building blocks for piperidine alkaloids synthesis and are prepared in
      high yields from the enzymatically derived cyclohept-3-ene-1,6-diol monoacetate (
      )-8. Efficient highly enantioselective syntheses of cis-4-hydroxypipecolic acid
      (1) and piperidines 3 and 4, in both enantiomeric forms, are described.
      [reaction: see text]

PMID- 11950366
TI  - Synthesis of new pyridines with oligocations and oxygen nucleophiles.
AB  - Nucleophilic substitution of 4-(dimethylamino)pyridine on pentachloropyridine
      yielded pentakis(pyridine-2,3,4,5,6-pentayl)pyridinium, tris-(3,5
      dichloropyridine-2,4,6-triyl)pyridinium, or (tetrachloropyridin-4-yl)pyridinium
      depending on the reaction conditions. Nucleophilic substitution with water,
      hydroxides, and alcoholates resulted in new betaines and highly substituted
      pyridines. [structure: see text]

PMID- 11950367
TI  - A convenient synthesis of a-ring-functionalized podolactones. Revision of the
      structure of wentilactone B.
AB  - A new route to podolactones functionalized in the A ring has been achieved. Two
      key steps were employed in this synthesis, the construction of the bicyclic
      skeleton via a Mn(III)-mediated radical cyclization and the transformation of
      this bicyclic intermediate into the tetracyclic podolactone skeleton through a Pd
      (II)-mediated bislactonization of the corresponding conjugate diene. The reported
      synthesis of 3beta-hydroxy-13,14,15,16-tetranorlabda-7,9(11)-dien
      (19,6beta),(12,17)-diolide (1) let us reassign the structure of wentilactone B,
      for which structure 1 was wrongly reported. [reaction: see text]

PMID- 11950368
TI  - The first stereoselective Ficini-Claisen rearrangement using chiral ynamides.
AB  - The first asymmetric Ficini-Claisen rearrangement using chiral ynamides is
      described. At relatively low temperatures, the Ficini-Claisen rearrangement can
      be efficiently promoted by p-nitrobenzenesulfonic acid leading to high
      diastereoselectivity for a range of different allylic alcohols and chiral
      ynamides. [reaction: see text]

PMID- 11950369
TI  - A convenient preparation of 3-substituted furans: synthesis of perillene and
      dendrolasin.
AB  - A variety of 3-substituted furans, including the natural products perillene and
      dendrolasin, are obtained in good yield via reductive annulation of 1,1,1
      trichloroethyl propargyl ethers using catalytic Cr(II) regenerated by Mn/TMSCl.
      [reaction: see text]

PMID- 11950370
TI  - Calix[4]arenes linked to multiple bidentate N-donors: potential ligands for
      synthetic modeling of multinuclear metalloenzymes.
AB  - A series of calix[4]arenes incorporating three or four bidentate diamines or
      pyridylamines attached at the "upper rim" were synthesized via practical
      protocols. Proof of structure was obtained in one instance by X-ray
      crystallography. These molecules are designed for general use as ligands for the
      preparation of multinuclear active site models of metalloenzymes. [reaction: see
      text]

PMID- 11950371
TI  - Directed evolution to generate cycloartenol synthase mutants that produce
      lanosterol.
AB  - Cycloartenol synthase converts oxidosqualene to cycloartenol, a pentacyclic
      isomer of the animal and fungal sterol precursor lanosterol. We used directed
      evolution to find cycloartenol synthase residues that affect cyclopropyl ring
      formation, selecting randomly generated cycloartenol synthase mutants for their
      ability to genetically complement a yeast strain lacking lanosterol synthase. To
      increase the likelihood of finding novel mutations, the little-studied
      Dictyostelium discoideum cycloartenol synthase was used for the mutagenesis.
      Several catalytically important residues were identified. [reaction: see text]

PMID- 11950372
TI  - Highly enantioselective diethylzinc addition to imines employing readily
      available N-monosubstituted amino alcohols.
AB  - An easily accessible chiral ligand 3c, which promoted diethylzinc addition to
      imines with 96-98% ee, has been found by finely screening N,N-disubstituted and N
      monosubstituted amino alcohols. N-monosubstituted amino alcohols, on average,
      gave slightly higher enantioselectivities than their N,N-disubstituted analogues.
      These results imply that the restricted and rigid structure of amino alcohol is
      not the absolute requirement for the highly enantioselective dialkylzinc addition
      to diphenylphosphinoylimines. [structure: see text]

PMID- 11950373
TI  - Tandem conjugate cyanide addition-Dieckmann condensation in the synthesis of the
      ABCD-ring system of lactonamycin.
AB  - An efficient synthesis of the ABCD-ring system of lactonamycin (1) is reported in
      this Letter. The key step is the tandem cyanide conjugate addition-Dieckmann
      condensation of alkyne 17 to afford a fully functionalized anthracene. Selective
      reduction of the cyano group with subsequent lactam formation affords the
      tetracyclic core of lactonamycin 19. [reaction: see text]

PMID- 11950374
TI  - Generation and reactions of a selenoamide dianion.
AB  - The selective generation of selenoamide monoanion and dianion was achieved by
      reacting N-benzyl selenobenzamide with BuLi. Alkylation of the dianion with 1
      equiv of electrophile took place at the carbon atom adjacent to the nitrogen
      atom, and subsequent hydrolysis produced functionalized selenoamides in good to
      high yields. Ring opening of oxiranes using the dianion proceeded with high regio
      and stereoselectivity to form N-3-hydroxy-1-phenylalkyl selenobenzamides. The
      stereochemistry of the major isomer derived from cyclohexene oxide was determined
      by X-ray molecular structure analysis. [reaction: see text]

PMID- 11950375
TI  - Kidney transplantation in older patients: benefits and risks.
AB  - The proportion of older patients accepted for dialysis is increasing every year
      both in the US and abroad. Of the two treatment modalities for end-stage renal
      disease, i.e. dialysis and transplantation, the latter offers more freedom and is
      associated with better clinical outcome. Most elderly patients seem to have
      excellent functional rehabilitation after a kidney transplant. However, in view
      of the wide gap between the availability of cadaver organs and the people in
      need, giving the precious organ to the elderly who have a shorter expected
      lifespan may present an ethical problem. Therefore, it has become increasingly
      important to offer the kidney to only those who have no significant comorbid
      conditions or other high risk factors, so as to improve the odds of success after
      renal transplantation.

PMID- 11950376
TI  - Thalidomide in cancer treatment: a potential role in the elderly?
AB  - There is increased interest in the treatment of cancer with thalidomide because
      of its antiangiogenic, immunomodulating and sedative effects. In animal models,
      the antitumour activity of thalidomide is dependent on the species, route of
      administration and coadministration of other drugs. For example, thalidomide has
      shown antitumour effects as a single agent in rabbits, but not in mice. In
      addition, the antitumour effects of the conventional cytotoxic drug
      cyclophosphamide and the tumour necrosis factor inducer 5,6-dimethylxanthenone-4
      acetic acid (DMXAA) were found to be potentiated by thalidomide in mice bearing
      colon 38 adenocarcinoma tumours. Further studies have revealed that thalidomide
      upregulates intratumoral production of tumour necrosis factor-alpha 10-fold over
      that induced by DMXAA alone. Coadministration of thalidomide also significantly
      reduced the plasma clearance of DMXAA and cyclophosphamide. All these effects of
      thalidomide may contribute to the enhanced antitumour activity. Recent clinical
      trials of thalidomide have indicated that it has minimal anticancer activity for
      most patients with solid tumours when used as a single agent, although it was
      well tolerated. However, improved responses have been reported in patients with
      multiple myeloma. Palliative effects of thalidomide on cancer-related symptoms
      have also been observed, especially for geriatric patients with prostate cancer.
      Thalidomide also eliminates the dose-limiting gastrointestinal toxic effects of
      irinotecan. There is preliminary evidence indicating that the clearance of
      thalidomide may be reduced in the elderly. The exact role of thalidomide in the
      treatment of cancer and cancer cachexia in the elderly remains to be elucidated.
      However, it may have some value as part of a multimodality anticancer therapy,
      rather than as a single agent.

PMID- 11950379
TI  - A Monte Carlo simulation for modelling outcomes of AIDS treatment regimens.
AB  - Healthcare providers are often faced with the need to make treatment decisions
      about antiretroviral therapy regimens for patients with HIV infection without
      definitive information as to the optimal sequencing of drug regimens. In this
      paper we describe our model developed to simulate the impact of differing drug
      sequencing strategies used in the treatment of patients with HIV/AIDS. In
      addition, we present the methods used to estimate the efficacy and duration of
      antiretroviral therapies to populate the model at baseline. We conducted a
      hypothetical application of the model using three alternative series of
      therapies: a series containing no drug therapy, a series starting with a protease
      inhibitor-containing regimen, and a series starting with a non-nucleoside reverse
      transcriptase inhibitor-containing regimen. The model described in this article
      can be used to compare and contrast the relative impact of different treatment
      guidelines in the absence of necessary clinical data and may serve as a means of
      evaluation until clinical trials or observational databases provide guidance as
      to the optimal treatment regimen(s). The model is flexible and permits adaptation
      to the changing treatment environment in HIV infection.

PMID- 11950378
TI  - Tamsulosin: a review of its pharmacology and therapeutic efficacy in the
      management of lower urinary tract symptoms.
AB  - Tamsulosin is a subtype-selective alpha(1A)- and alpha(1D )-adrenoceptor
      antagonist. alpha(1)-Receptors predominate in the prostate gland, prostatic
      capsule, prostatic urethra and bladder, and the relaxation of prostate and
      bladder smooth muscles is associated with improved maximal urine flow (Q(max))
      and alleviation of lower urinary tract symptoms (LUTS) in patients with benign
      prostatic hyperplasia (BPH). Tamsulosin 0.4 mg once daily in a modified-release
      formulation increased Q(max) and improved symptom scores relative to baseline to
      a greater extent than placebo in 12- and 13-week double-blind, randomised,
      multicentre, clinical trials in patients with LUTS, with statistical significance
      between treatments for Q(max) values in two of three published US and European
      studies. Tamsulosin is effective in patients with mild to severe LUTS associated
      with BPH, in patients with diabetes mellitus and in the elderly, and does not
      interfere with concomitant antihypertensive therapy. Pooled data based on
      patients receiving tamsulosin 0.4 or 0. 8mg once daily indicate maintenance of
      efficacy for up to 6 years. Tamsulosin 0.4 mg once daily was of similar efficacy
      to alfuzosin 2.5 mg three times daily, with less tendency to cause hypotensive
      effects, in a double-blind, randomised 12-week trial. Benefit of the drug has
      also been shown in patients with acute urinary retention or chronic abacterial
      prostatitis, those receiving high energy transurethral microwave thermotherapy,
      and in patients with prostate cancer with radiation-induced urethritis. Dizziness
      and abnormal ejaculation are stated to be the most common adverse events, with
      asthenia, postural hypotension and palpitations being seen less frequently (1 to
      2% incidence), in patients receiving tamsulosin 0.4 mg once daily. Tamsulosin has
      not been associated with clinically significant changes in blood pressure in
      clinical trials. CONCLUSION: The alpha(1A)- and alpha(1D)-adrenoceptor antagonist
      tamsulosin, given at a dosage of 0.4 mg once daily in a modified-release
      formulation, is effective and well tolerated in the treatment of LUTS associated
      with BPH. Although the drug has been directly compared to date with one other
      agent only, data show overall that tamsulosin clearly offers advantages over
      other alpha(1)-adrenoceptor antagonists in terms of the need for a single daily
      dose only, and its low potential for hypotensive effects or interference with
      concomitant antihypertensive therapy. Dosage titration at the start of treatment
      is not necessary. Tamsulosin has a rapid onset of action and is effective in
      patients with moderate or severe symptoms. The drug is therefore a valuable
      therapeutic option, with both demonstrated and potential advantages over older
      nonselective agents, in the management of patients with LUTS associated with BPH.

PMID- 11950381
TI  - Putting your money where your mouth is: willingness to pay for dental gel.
AB  - OBJECTIVES: To measure preferences and willingness to pay (WTP) for a novel
      anaesthetic (dental gel) versus existing anaesthetic options for periodontal
      maintenance visits. DESIGN: The study was conducted by developing and
      administering a survey, composed of a modified decision aid and a WTP instrument.
      The decision aid provided clinical information in layman's terms. Patients stated
      their anaesthetic preference; WTP elicited the hypothetical amount of money a
      subject would pay to have dental gel available for maintenance cleaning, should
      they require anaesthetic. PATIENTS: Periodontal recall patients (n = 97;
      'recall') and participants from the general population (n = 196; 'general') from
      southwestern Ontario, Canada. RESULTS: The overwhelming majority of participants
      chose dental gel over injectable local anaesthetic or no anaesthetic as their
      first anaesthetic preference (general: 81.0%; recall: 82.5%). The median WTP for
      dental gel was 20.00 Canadian dollars (dollars Can) per visit for the general
      population and dollars Can10.00 for the recall population (1999 values). The
      majority of participants were willing to pay an insurance premium for dental gel,
      even if they did not personally prefer dental gel (general: 72.4%; recall:
      73.2%). The median monthly premium to have dental gel available for any plan
      beneficiary requiring scaling and root planing (SRP) during maintenance was
      dollars Can2.00 per month for both groups. CONCLUSIONS: In this population, an
      alternative to traditional injectable local anaesthetic (i.e. dental gel) was
      overwhelmingly preferred by both general population participants and recall
      patients for maintenance cleaning procedures. Most participants were willing to
      pay to have dental gel available, either for themselves or for others.

PMID- 11950382
TI  - Assessment of the relationship between measures of disease severity, quality of
      life, and willingness to pay in asthma.
AB  - OBJECTIVE: The primary objective was to evaluate the relationship between
      willingness-to-pay (WTP), quality-of-life (QOL), and disease-severity measures in
      patients with asthma. The hypothesis studied was that patients with asthma with
      more severe disease are willing to pay more for a hypothetical cure of asthma
      than those with less severe disease. DESIGN SETTING/PATIENTS AND PARTICIPANTS:
      One hundred patients with asthma were recruited from community pharmacies in
      Kentucky for 30-minute face-to-face interviews. INTERVENTIONS: Spirometry
      assessed objective disease severity in terms of pulmonary function, while a
      multiple choice question measured subjective disease severity. The Medical
      Outcomes Study 36-item Short Form (SF-36) health survey and Asthma Technology of
      Patient Experience (Asthma TyPE) measured quality of life. WTP was obtained via a
      dichotomous choice contingent valuation question. RESULTS: In this exploratory
      evaluation, WTP was significantly related to both objective disease severity (p =
      0.02) and subjectively assessed disease severity (p = 0.01). For objective
      disease severity the mean monthly WTP was dollars US90 for mild asthma, dollars
      US131 for moderate asthma and dollars US331 for severe asthma and for subjective
      disease severity the mean monthly WTP was dollars US48 for mild asthma, dollars
      US166 for moderate asthma and dollars US241 for severe asthma. CONCLUSIONS: The
      results suggest that the WTP for a cure from asthma is related to both objective
      and subjective disease severity. These findings contribute to the case for
      construct validity of the dichotomous choice contingent valuation method in the
      healthcare sector.

PMID- 11950380
TI  - Enoxaparin: a pharmacoeconomic review of its use in the prevention and treatment
      of venous thromboembolism and in acute coronary syndromes.
AB  - The pharmacoeconomics of the low molecular weight heparin (LMWH) enoxaparin in
      the prophylaxis and treatment of venous thromboembolism have mostly been
      investigated in cost-effectiveness studies that estimated direct costs associated
      with treatment, using decision analyses and clinical outcome data from randomised
      controlled trials. These studies have shown enoxaparin to be cost effective
      compared with unfractionated heparin (UFH) and warfarin in short-term
      thromboprophylaxis for hospital inpatients undergoing orthopaedic surgery and in
      thromboprophylaxis following trauma. Outpatient treatment of acute proximal deep
      vein thrombosis with enoxaparin has also been shown to be cost effective compared
      with inpatient treatment using UFH. In general surgery, however, it remains to be
      determined whether enoxaparin is a cost-effective alternative to UFH. The cost
      effectiveness of enoxaparin compared with UFH in the treatment of unstable angina
      and non-Q-wave myocardial infarction has also been investigated in several
      countries using clinical outcomes data from the Efficacy and Safety of
      Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) randomised trial.
      ESSENCE demonstrated that enoxaparin was superior to UFH in terms of tolerability
      and efficacy, and cost saving at both 30-day and 1-year follow-ups. An increasing
      number of studies indicate enoxaparin to be of economic benefit when used for
      prevention and treatment of venous thromboembolism and treatment of acute
      coronary symdromes.

PMID- 11950383
TI  - Cost effectiveness of proton pump inhibitors in gastro-oesophageal reflux disease
      without oesophagitis: comparison of on-demand esomeprazole with conventional
      omeprazole strategies.
AB  - OBJECTIVES: To evaluate the cost effectiveness of on-demand treatment with
      esomeprazole 20mg compared with two alternative omeprazole treatment strategies
      for the long-term management of patients with gastro-oesophageal reflux disease
      (GORD) without oesophagitis. DESIGN: A simple Markov model was designed to
      compare the cost effectiveness of on-demand esomeprazole 20mg therapy for 6
      months with a strategy consisting of intermittent 4-week acute treatment courses
      of omeprazole 20mg once daily or a strategy consisting of continuous omeprazole
      treatment (20mg once daily) following acute treatment of first relapse while on
      no drug treatment (a commonly used conventional care strategy). Relapse
      probabilities were based on pooled results from two 6-month placebo-controlled
      clinical studies of on-demand esomeprazole 20mg treatment in patients with GORD
      without oesophagitis and on results from a GORD study with a 6-month untreated
      follow-up. The expected number of relapses per patient was used as the
      effectiveness measure. SETTING AND PERSPECTIVE: Patient management assumptions
      were based on a UK physician survey. The cost-effectiveness analysis considered
      UK direct medical costs from the perspective of the National Health Service.
      RESULTS: The pooled analysis showed that after 6 months treatment, 90% of
      patients could control symptoms effectively with on-demand esomeprazole 20mg. The
      expected number of relapses per patient was estimated at 0.10 for on-demand
      esomeprazole, 0.57 to 1.12 for intermittent omeprazole and 0.47 to 0.75 for
      conventional omeprazole treatment. The esomeprazole strategy incurred
      considerably lower direct medical costs (16 to 61%) than either omeprazole
      strategy. CONCLUSION: On-demand treatment with esomeprazole 20mg is cost
      effective compared with two alternative omeprazole treatment strategies in
      patients with GORD without oesophagitis.

PMID- 11950384
TI  - Cost effectiveness of esomeprazole compared with omeprazole in the acute
      treatment of patients with reflux oesophagitis in the UK.
AB  - BACKGROUND: Clinical studies have demonstrated that esomeprazole is superior to
      omeprazole for the acute treatment of reflux oesophagitis. OBJECTIVE: To compare
      the cost effectiveness of esomeprazole 40mg once daily with omeprazole 20mg once
      daily in patients with reflux oesophagitis. METHODS: Pooled data were used from
      three 8-week clinical trials comparing the efficacy and safety of esomeprazole
      40mg once daily and omeprazole 20mg once daily for the acute treatment of reflux
      oesophagitis. A simple decision analysis model, using UK direct medical costs,
      compared the cost effectiveness of the two treatments. Healing probabilities
      derived from the clinical studies using the Life Table method were used to
      estimate the effectiveness and cost of treating 100 patients with reflux
      oesophagitis. Patient management assumptions were based on a clinical management
      survey involving 25 UK physicians. PERSPECTIVE: UK National Health Service.
      RESULTS: After 4 weeks' therapy, the Life Table estimated the oesophageal healing
      rate to be 77.7% in esomeprazole 40mg once-daily recipients (n = 2446), compared
      with 67.6% in omeprazole 20mg once-daily recipients (n = 2431; p < 0.001). The
      corresponding values after 8 weeks' treatment were 93.4% and 86.2%, respectively
      (p < 0.001). The model predicted that when considering healing probabilities over
      8 weeks, esomeprazole 40mg once daily produced total direct cost savings of
      pound1290 (14%) when compared with omeprazole 20mg once daily. When considering
      the cost of treating patients who had failed treatment (defined as patient not
      healed as assessed by endoscopy) after 8 weeks, the cost advantage for
      esomeprazole was even greater. CONCLUSION: Esomeprazole 40mg once daily is cost
      effective compared with omeprazole 20mg once daily in the acute treatment of
      patients with reflux oesophagitis; esomeprazole provides greater effectiveness at
      a lower cost.

PMID- 11950385
TI  - Disparities in oral health and access to care: findings of national surveys.
AB  - In this background paper, sociodemographic variables, including age, race, family
      income, sex, parental education, and geographic location, have been used to
      characterize the dental status of US children and their access to dental
      services. Because tooth decay, or dental caries, remains the preeminent oral
      disease of childhood and national data is available on dental office visits,
      tooth decay has been used as the primary marker for children's oral health, and
      visits to the dentist is the marker for care. In general, children from low
      income families experience the greatest amount of oral disease, the most
      extensive disease, and the most frequent use of dental services for pain relief.
      Yet these children have the fewest overall dental visits. Paradoxically, children
      in poverty-those living in households with annual gross incomes under $16 500 for
      a family of 4-or near poverty-those in family households with incomes between $16
      500 and $33 000-also have the highest rates of dental insurance coverage,
      primarily through Medicaid and SCHIP. For those most affected, dental disease is
      consequential for their growth, function, behavior, and comfort. The twin
      disparities of poor oral health and lack of dental care are most evident among
      low-income preschool children, who are twice as likely to have cavities as are
      higher income children. Medicaid-eligible children who have cavities have twice
      the numbers of decayed teeth and twice the number of visits for pain relief but
      fewer total dental visits, compared to children coming from families with higher
      incomes. Fewer preventive visits for services such as sealants increase the
      burden of disease in low-income children. These disparities continue into
      adolescence and young adulthood, but to a lesser degree. Disparities in oral
      health status and access to dental care are also evident when comparing black,
      Hispanic, and Native American children to white children and when comparing
      children of parents with low educational attainment to children of parents with
      higher educational attainment. The fastest growing populations of children are
      those that currently have the highest disease rates and the lowest amount of
      dental care. If the strong correlation between these subpopulations and dental
      diseases continues, caries rates are likely to rebound after longstanding
      declines, and the stress on publicly financed dental care will likely increase.

PMID- 11950386
TI  - Children's oral health services: organization and financing considerations.
AB  - This article highlights prominent issues concerning children's oral health and
      provides an overview of the structure, organization, and financing of dental
      services for children in the United States. The size, composition,
      characteristics, and distribution of the dental workforce and the arrangements
      that facilitate the delivery and financing of dental services are discussed.
      Features of the current dental care delivery system are examined within the
      context of primary care. Suggestions for creating meaningful change to enhance
      access through expanded, integrated systems are presented as part of a concluding
      challenge.

PMID- 11950387
TI  - Dental workforce trends and children.
AB  - Trends in the US dental workforce that may affect oral health services for
      children are reviewed. Overall, the number of graduates from dental schools has
      declined significantly over the past 13 years. Between 1986 and 1993, 6 dental
      schools have closed their doors, and one more has closed in 2001; only one new
      school opened during this time. The remaining US dental schools have experienced
      reductions in class sizes, and the percentage of graduating dentists declined by
      40% between 1986 and 2000. Diversity in the dental profession also remains a
      concern. Less than 5% of incoming dental students are African American, and less
      than 5% are Hispanic/Latino. These percentages are far below the overall US
      population of African Americans (12%) and Hispanic/Latinos (11%). Currently,
      projections of future workforce needs are mixed and uncertain. The need for
      dental services is quite variable and is highly dependent on the economy. Good
      economic times tend to create a high demand for dental care. As the need for
      dental services increases, the greater the strain on the dental workforce. This
      decline in dental personnel and services may have far-reaching consequences among
      indigent populations, particularly for children from low-income families. Thus,
      the ability of the current workforce to respond to the dental needs of the US
      population is compromised by a number of factors. These factors may affect the
      ability of the workforce to respond to the needs of vulnerable populations;
      children with a high prevalence of dental caries present an especially daunting
      problem.

PMID- 11950388
TI  - Ethical principles and the delivery of children's oral health care.
AB  - Fundamental ethical principles provide a framework for evaluating children's oral
      health care and current policies. Principles of justice reveal fundamental
      inequities in the delivery of children's oral health care. The dental care
      delivery system rations services by ability to pay and personal choice and places
      at a disadvantage children who are in the poorest age group, who do not make
      their own decisions, and who depend upon adults for access to health care. All
      major theories of justice are consistent with a societal obligation to provide
      basic health care for children, including oral health care. Beneficence requires
      physicians and dentists to help the individual child-patient but also obligates
      others and the society to advocate for children in view of their vulnerability
      and the importance of oral health to their well-being and future opportunities.
      Respect for autonomy requires that decisions about children's health care be made
      in the best interests of the child and in conjunction with families. Such
      decisions will be grounded in the context of the child's development and his
      social, family, cultural, and environmental circumstances. Advocacy for a just
      distribution of resources to children is morally required of physicians and
      dentists in view of the professions' implicit contract to serve society, public
      funding of professional education, and the professionals' special knowledge of
      children's health needs. Pediatricians in particular have an important role to
      play but often lack the knowledge to promote or effectively advocate for
      children's oral health. Conversely, dentists may not fully understand critical
      contextual issues in children's lives.

PMID- 11950389
TI  - Demographic and social trends affecting the health of children in the United
      States.
AB  - This article provides information on key demographic, social, and economic
      characteristics of children in the United States that affect the child's health
      and access to health insurance. The data, drawn principally from the March 1999
      supplement to the Current Population Survey (CPS), focus on racial/ethnic groups
      and generational categories (i.e., immigrants, US natives with foreign-born
      parents, and US natives with native parents). The article investigates the
      relationship of socioeconomic status, race/ethnicity, and generation to self
      reported health status, health insurance coverage, and use of Medicaid. In
      general, racial/ethnic minority children and children of immigrants report being
      in worse health and are less likely to have health insurance than are white, non
      Hispanic children and children of US natives. However, much of the difference can
      be explained by income differences across the racial/ethnic and generation
      groups. Citizenship of a child's parents is also a key factor in health insurance
      coverage. The article closes with a discussion of how likely demographic trends
      over the next 10-25 years may affect these factors, especially noting the
      competing demands of children and the elderly on the future working-age
      population.

PMID- 11950377
TI  - Age-related macular degeneration: epidemiology and optimal treatment.
AB  - Age-related macular degeneration (AMD) is a common macular disease affecting
      elderly people in the Western world. It is characterised by the appearance of
      drusen in the macula, accompanied by choroidal neovascularisation (CNV) or
      geographic atrophy. The disease is more common in Caucasian individuals than in
      pigmented races. In predominantly Caucasian populations, the age-standardised
      prevalence of AMD in at least one eye is 7760 cases per million. The age
      standardised cumulated 1-year incidence of AMD in at least one eye is 1051 cases
      per million individuals. AMD is the most important single cause of blindness
      among Caucasian individuals in developed countries. Blindness resulting from AMD
      rarely occurs before age 70, and most cases occur after age 80. The age
      standardised 1-year incidence of legal blindness resulting from AMD is 212 cases
      per million. Two-thirds of AMD cases have CNV (exudative cases); the remainder
      has only geographic atrophy. In cross-sectional population-based studies about
      45% of eyes with AMD have visual acuity reduced to 20/200 or worse. This is true
      both for exudative AMD and pure geographic atrophy. Age and genetic
      predisposition are known risk factors for AMD. Smoking is probably also a risk
      factor. Preventive strategies using macular laser photocoagulation are under
      investigation, but their efficacy in preventing visual loss is as yet unproven.
      There is no treatment with proven efficacy for geographic atrophy. Optimal
      treatment for exudative AMD requires a fluorescein angiographic study and a
      physician capable of interpreting it. For CNV not involving the foveal centre,
      the only evidence-based treatment is laser photocoagulation. For AMD cases with
      subfoveal CNV, good visual acuity, and predominantly classic fluorescence pattern
      on fluorescein angiography, photodynamic therapy with verteporfin is the
      treatment of choice. Photodynamic therapy is also effective in eyes with pure
      occult CNV and evidence of recent disease progression. For new subfoveal CNV with
      poor vision and recurrent CNV, laser photocoagulation can be considered.

PMID- 11950390
TI  - Strategic communications in oral health: influencing public and professional
      opinions and actions.
AB  - In the spring of 2000, US Surgeon General Dr. David Satcher convened a meeting of
      national experts to recommend strategies to promote equity in children's oral
      health status and access to dental care. The meeting was planned by a diverse
      group of health professionals, researchers, educators, and national organizations
      and by several federal agencies, including the Centers for Disease Control and
      Prevention, the Center on Medicare and Medicaid Services, the Health Resources
      and Services Administration, and the National Institute of Dental and
      Craniofacial Research, National Institutes of Health. This paper was commissioned
      by the meeting planners to introduce basic principles of social marketing and
      strategic communications. Many participants were academic researchers, practicing
      pediatric dentists and pediatricians, dental educators, policy analysts, and
      industry representatives, and most had no previous experience with public
      education or communications campaigns. Other participants were communications
      professionals, journalists, and community organizers without previous experience
      in oral health care or financing issues. Thus, the paper also served to introduce
      and illustrate basic ideas about oral health and general health, racial and
      ethnic disparities in health, and access to care. Through their interactions, the
      participants developed a series of recommendations to increase public awareness,
      build public support, improve media coverage, improve care coordination, expand
      the workforce, and focus the attention of national, state, and local policymakers
      on legislative and financing initiatives to expand access to dental care. Future
      coalitions of health professionals working with the policy, research, advocacy,
      and business communities may find this paper useful in implementing the action
      steps identified by the Surgeon General's report, "Oral Health in America."

PMID- 11950391
TI  - Activation of glucokinase gene expression by hepatic nuclear factor 4alpha in
      primary hepatocytes.
AB  - Glucokinase (GK) is a key enzyme for glucose utilization in liver and shows a
      higher expression in the perivenous zone. In primary rat hepatocytes, the GK gene
      expression was activated by HNF (hepatic nuclear factor)-4alpha via the sequence 
      52/-39 of the GK promoter. Venous pO2 enhanced HNF-4 levels and HNF-4 binding to
      the GK-HNF-4 element. Thus, HNF-4alpha could play the role of a regulator for
      zonated GK expression.

PMID- 11950392
TI  - GGA proteins associate with Golgi membranes through interaction between their
      GGAH domains and ADP-ribosylation factors.
AB  - ADP-ribosylation factors (ARFs) are a family of small GTPases that are involved
      in various aspects of membrane trafficking events. These include ARF1-ARF6, which
      are divided into three classes on the basis of similarity in the primary
      structure: Class I, ARF1-ARF3; Class II, ARF4 and ARF5; and Class III, ARF6.
      Previous studies identified a novel family of potential ARF effectors, termed
      GGA1-GGA3, which interact specifically with GTP-bound ARF1 and ARF3 and are
      localized to the trans-Golgi network (TGN) or its related compartment(s) (GGA is
      an abbreviation for Golgi-localizing, gamma-adaptin ear homology domain, ARF
      binding protein). In the present study we have shown that ARF proteins belonging
      to the three classes, ARF1, ARF5 and ARF6, can interact with all GGA proteins in
      a yeast two-hybrid assay, in vitro and in vivo. Segmentation of GGA proteins and
      isolation of GGA mutants defective in ARF binding have revealed that a limited
      region within the GGA homology domain, which is conserved in the GGA family, is
      essential for ARF binding. Expression in cells of GTPase-restricted mutants of
      ARF1 and ARF5 blocks dissociation of GGA proteins from membranes induced by
      brefeldin A. However, neither of the ARF mutants recruits GGA mutants defective
      in ARF binding. On the basis of these observations, we conclude that at least
      ARF1 (Class I) and ARF5 (Class II) in their GTP-bound state cause recruitment of
      GGA proteins on to TGN membranes. In contrast, on the basis of similar
      experiments, ARF6 (Class III) may be involved in recruitment of GGA proteins to
      other compartments, possibly early endosomes.

PMID- 11950394
TI  - The significance of opthalmologic evaluation in the early diagnosis of inborn
      errors of metabolism: the Cretan experience.
AB  - BACKGROUND: The Inborn Errors of Metabolism (IEM) are far from the rare systemic
      diseases that mainly affect the neural tissue. There are very few written reports
      on ocular findings in subjects with IEM, thus it was interesting to study the
      frequency of ocular findings in the studied population and explore their
      contribution to the early diagnosis of IEM. METHODS: Our study involved the
      evaluation of IEM suspected cases, which had been identified in a rural
      population in Crete, Greece. Over a period of 3 years, 125 patients, who
      fulfilled the inclusion criteria of this study, were examined. Analytical
      physical examination, detailed laboratory investigation as well as a thorough
      ocular examination were made. RESULTS: A diagnosis of IEM was established in 23
      of the 125 patients (18.4%). Ten (43.5%) of the diagnosed IEM had ocular
      findings, while 8 of them (34.8%) had findings which were specific for the
      diagnosed diseases. One patient diagnosed with glycogenosis type 1b presented a
      rare finding. Of the 102 non-diagnosed patients, 53 (51.96 %) presented various
      ophthalmic findings, some of which could be related to a metabolic disease and
      therefore may be very helpful in the future. CONCLUSIONS: The ocular
      investigation can be extremely useful for raising the suspicion and the
      establishment of an early diagnosis of IEM. It could also add new findings
      related to these diseases. The early management of the ocular symptoms can
      improve the quality of life to these patients.

PMID- 11950393
TI  - A cross-sectional study of early identification of postpartum depression:
      implications for primary care providers from The Ontario Mother & Infant Survey.
AB  - BACKGROUND: This survey's objective was to provide planning information by
      examining utilization patterns, health outcomes and costs associated with
      existing practices in the management of postpartum women and their infants. In
      particular, this paper looks at a subgroup of women who score >or= 12 on the
      Edinburgh Postnatal Depression Survey (EPDS). METHODS: The design is cross
      sectional with follow-up at four weeks after postpartum hospital discharge. Five
      Ontario hospitals, chosen for their varied size, practice characteristics, and
      geographic location, provided the setting for the study. The subjects were 875
      women who had uncomplicated vaginal deliveries of live singleton infants. The
      main outcome measures were the EPDS, the Duke UNC Functional Social Support
      Questionnaire and the Health and Social Services Utilization Questionnaire.
      RESULTS: EPDS scores of >or= 12 were found in 4.3 to 15.2% of otherwise healthy
      women. None of these women were being treated for postpartum depression. Best
      predictors of an EPDS score of >or= 12 were lack: of confident support, lack of
      affective support, household income of <20,000 dollars, wanting to stay in
      hospital longer, identification of learning needs while in hospital, self
      identified care needs for an emotional/mental health problem that have not been
      met and mother's rating of own and baby's health as fair or poor. CONCLUSIONS:
      Primary care physicians, midwives, and public health nurses need to screen for
      depression at every opportunity early in the postpartum period. A mother's
      expression of undue concern about her own or her baby's health may be predictive
      of postpartum depression. Flexible, mother-focused support from community
      providers may decrease the prevalence of postpartum depression.

PMID- 11950395
TI  - Head injury and posttraumatic movement disorders.
AB  - WE REVIEW THE phenomenology, pathophysiology, pathological anatomy, and therapy
      of posttraumatic movement disorders with special emphasis on neurosurgical
      treatment options. We also explore possible links between craniocerebral trauma
      and parkinsonism. The cause-effect relationship between head injury and
      subsequent movement disorder is not fully appreciated. This may be related
      partially to the delayed appearance of the movement disorder. Movement disorders
      after severe head injury have been reported in 13 to 66% of patients. Although
      movement disorders after mild or moderate head injury are frequently transient
      and, in general, do not result in additional disability, kinetic tremors and
      dystonia may be a source of marked disability in survivors of severe head injury.
      Functional stereotactic surgery provides long-term symptomatic and functional
      benefits in the majority of patients. Thalamic radiofrequency lesioning, although
      beneficial in some patients, frequently is associated with side effects such as
      increased dysarthria or gait disturbance, particularly in patients with kinetic
      tremor secondary to diffuse axonal injury. Deep brain stimulation is used
      increasingly as an option in such patients. It remains unclear whether pallidal
      or thalamic targets are more beneficial for treatment of posttraumatic dystonia.
      Trauma to the central nervous system is an important causative factor in a
      variety of movement disorders. The mediation of the effects of trauma and the
      pathophysiology of the development of posttraumatic movement disorders require
      further study. Functional stereotactic surgery should be considered in patients
      with disabling movement disorders refractory to medical treatment.

PMID- 11950396
TI  - Patient-evaluated outcome after surgery for basal meningiomas.
AB  - OBJECTIVE: To study the outcomes of patients with basal meningiomas treated by
      one primary surgeon with a philosophy of aggressive surgical management to
      establish an index of satisfaction and patient-evaluated outcome. METHODS: We
      collected prospective data for patients with basal meningiomas who were operated
      on by one primary surgeon (LNS) during a 7-year period from 1993 to 2000. The
      outcomes in 269 patients were ascertained through follow-up visits, mailed follow
      up questionnaires, and telephone interviews by two other surgeons (RA and MN).
      The mean patient age was 50 +/- 13.6 years. The mean estimated tumor diameter was
      3.07 +/- 1.24 cm. There were 62 males and 207 females. Mean follow-up was 49 +/-
      26 months. Twenty-seven percent of patients were Levine-Sekhar (LS) Grade 0, 43%
      were LS Grade I, 24% were LS Grade II, and 6% were LS Grade III. Gross total
      resection was achieved in 66% of patients. Extent of resection correlated (P <
      0.05) with LS grade. Thirty-seven patients received adjuvant treatments, and six
      patients required reoperations. Perioperative mortality was 1.1%. Eighty percent
      of patients were discharged home, 17% were discharged to rehabilitation
      facilities, and 1.5% were discharged to nursing homes. Postoperative
      complications were observed in 30% of patients. RESULTS: During the follow-up
      study, of a total of 269 patients, 30 patients could not be contacted, and 11
      patients had died of unrelated causes. The mean follow-up Karnofsky Performance
      Scale score of the patients was 83 +/- 10. Ninety-seven percent of patients were
      very satisfied/satisfied with their treatments (P < 0.001). Forty-three percent
      of patients were employed, and 83% of patients were employable. Their
      expectations of treatment were met in 90% of patients (P < 0.001), 95% thought
      surgery had been a good treatment choice (P < 0.001), and 95% would recommend the
      same treatment for a family member (P < 0.001). CONCLUSION: These results
      demonstrate that patient satisfaction can remain high and satisfactory outcome
      can be achieved with surgical management in patients with these complex lesions.

PMID- 11950397
TI  - Optic nerve sheath meningiomas: visual improvement after stereotactic
      radiotherapy.
AB  - OBJECTIVE: The management of primary optic nerve sheath meningioma (ONSM) is
      controversial. Surgery often results in postoperative blindness in the affected
      eye and thus has been abandoned as a treatment option for most patients. When
      these tumors are left untreated, however, progressive visual impairment ensues,
      which also leads to blindness. Recently, radiation therapy has gained wider
      acceptance in the treatment of these lesions. Experience with stereotactic
      radiotherapy (SRT) in the treatment of ONSMs is limited because of the rare
      incidence of this tumor. We present a series of patients with ONSM who were
      treated with SRT. METHODS: Five patients (three women, two men), ranging in age
      from 40 to 73 years, presented with progressive visual loss with decreased visual
      field, visual acuity, and color vision affecting six eyes (one patient had tumor
      involving both optic nerves). One patient also presented with proptosis and
      diplopia. Five eyes had functional residual vision (range, 20/20 to 20/40), and
      one eye was completely blind. All five patients were diagnosed clinically and
      radiographically to have an ONSM. Three were intraorbital, one was
      intracanalicular as well as intraorbital, and one was a left ONSM extending
      through the optic foramen into the intracranial space and involving the right
      optic nerve. The five functional eyes were treated with SRT by use of 1.8-Gy
      fractions to a cumulative dose of 45 to 54 Gy. RESULTS: Follow-up ranged from 1
      to 7 years, and serial magnetic resonance imaging revealed no changes in the size
      of the tumor in all five patients. Four patients experienced dramatic improvement
      in visual acuity, visual field, and color vision within 3 months after SRT. One
      patient remained stable without evidence of visual deterioration or disease
      progression. None had radiation-induced optic neuropathy. CONCLUSION: SRT may be
      a viable option for treatment of primary ONSM in patients with documented
      progressive visual deterioration, and it may be effective in improving or
      stabilizing remaining functional vision.

PMID- 11950399
TI  - Surgical resection of grade II astrocytomas in the superior frontal gyrus.
AB  - OBJECTIVE: Surgery in the superior frontal gyrus partially involving the
      supplementary motor area (SMA) may be followed by contralateral transient
      weakness and aphasia initially indistinguishable from damage to the primary motor
      cortex. However, recovery is different, and SMA deficits may resolve completely
      within days to weeks. No study has assessed the distinct postoperative deficits
      after tumor resection in the SMA on a homogeneous patient group. METHODS: Twenty
      four patients with World Health Organization Grade II astrocytomas in the
      superior frontal gyrus consecutively treated by surgery were studied. Degree and
      duration of postoperative deficits were evaluated according to tumor location and
      boundaries via magnetic resonance imaging scans, intraoperative neuromonitoring
      results, and extent of tumor resection. RESULTS: Postoperatively, motor deficits
      were evident in 21 of 24 and speech deficits in 9 of 12 patients. Motor function
      quickly recovered in 11 and speech function in 3 patients. None of the 12
      patients in whom the posterior tumor resection line was at a distance of more
      than 0.5 cm from the precentral sulcus experienced persistent motor deficits.
      Eight of these patients developed typical SMA syndrome with transient initiation
      difficulties. Seven of 12 patients in whom the tumor extended to the precentral
      sulcus still had motor deficits at the 12-month follow-up assessment. CONCLUSION:
      Surgery for Grade II gliomas in the superior frontal gyrus is more likely to
      result in permanent morbidity when the resection is performed at a distance of
      less than 0.5 cm from the precentral gyrus or positive stimulation points.
      Therefore, cortical mapping of motor and speech function, in critical cases under
      local anesthesia with the patient as his or her own monitor, is recommended;
      resection should be tailored to obtain good functional outcome and maintain
      quality of life.

PMID- 11950398
TI  - Prognostic significance of amino acid transport imaging in patients with brain
      tumors.
AB  - OBJECTIVE: To evaluate the prognostic significance of presence, intensity, and
      extent of amino acid uptake in patients with suspected primary or recurrent brain
      tumors. METHODS: We retrospectively analyzed 181 consecutive studies of amino
      acid uptake using single-photon emission computed tomography and the amino acid l
      [3-(123)I]iodo-alpha-methyltyrosine (IMT). In a blinded analysis, all studies
      were evaluated for presence, maximal uptake (IMT(max)), and extent (IMT(ext)) of
      focal tracer uptake. RESULTS: The most frequent tumors were 53 astrocytomas
      (World Health Organization Grade I-III), 41 glioblastomas, 16 metastases, 13
      oligodendrogliomas (Grade II-III), and 10 medulloblastomas. The other patients
      exhibited various parenchymal tumors or nonneoplastic lesions. IMT uptake was
      present in 69% of the patients with IMT(max) ranging from 1.4 to 6.2. IMT(max)
      and IMT(ext) were significant predictors of survival in the whole group. When the
      group was divided according to primary versus recurrent tumor, only the primary
      tumors achieved a high level of significance (P < 0.01). When patients without
      any IMT uptake were excluded from the analysis, statistical significance for both
      IMT(max) and IMT(ext) was lost. Multiple regression analysis, including IMT(max),
      IMT(ext), age, and tumor grade, revealed only extent of IMT uptake as an
      independent predictor of prognosis. CONCLUSION: Absence of IMT uptake is a
      significant predictor of long-term survival in patients with suspected primary or
      recurrent brain tumors. Only the extent of a given lesion provided minor
      supplementary prognostic information as compared with histopathology and age.
      These findings suggest caution in relating high amino acid uptake values to poor
      prognosis, despite the capability of amino acid imaging to help determine the
      presence and extent of gliomas.

PMID- 11950400
TI  - Volumetric stereotaxy and the supratentorial occipitosubtemporal approach in the
      resection of posterior hippocampus and parahippocampal gyrus lesions.
AB  - OBJECTIVE: Resection of intracranial tumors in the posterior hippocampus and the
      parahippocampal gyrus can be associated with significant morbidity because of the
      parenchymal resection and the cortical retraction often required in gaining
      access to this infrequently explored region. With the use of image guidance, the
      occipitosubtemporal (OST) approach requires neither lateral cortical resection
      nor the placement of brain retractors to gain surgical access to the posterior
      hippocampus and the parahippocampal gyrus, and this approach is associated with a
      high rate of gross total tumor resection. METHODS: The computer-assisted
      volumetric stereotactic OST approach was used to resect 40 posterior hippocampus
      and parahippocampal gyrus tumors in 34 consecutive patients during an 8-year
      period. Patient, radiographic, and surgical outcome data were collected
      retrospectively. RESULTS: The series included operations in 25 men and 15 women,
      and the patients' average age was 40.3 years (range, 15-69 yr). Twenty-five of
      the 40 procedures were performed to remove lesions in the dominant hemisphere,
      and previous craniotomies for resection had been performed in 12 of 40 cases. In
      38 of 40 cases, histopathological analysis revealed a glial neoplasm, and 50% of
      these tumors were high-grade lesions. Preoperatively, 23 patients were
      neurologically intact before 40 procedures, whereas visual field deficits were
      noted in 7 patients, mild hemiparesis was documented in 4 patients, and other
      neurological deficits were present in 9 patients. An excellent outcome (Glasgow
      Outcome Scale Grade 5) was noted after 38 (95%) of the 40 computer-assisted
      volumetric stereotactic OST procedures. Permanent postoperative hemiparesis
      (Glasgow Outcome Scale Grade 4) occurred after one procedure, and a second
      patient, despite being neurologically unchanged postoperatively and despite
      having had an optimal tumor resection, died on postoperative Day 33 (Glasgow
      Outcome Scale Grade 1). Complete resection of the preoperatively defined tumor
      volume was noted on postoperative gadolinium-enhanced magnetic resonance imaging
      examinations after 39 (97.5%) of the 40 procedures. The average duration of
      clinical follow-up was 15.9 months (range, 0.5-67 mo). CONCLUSION: We think that
      the OST approach is well suited to the resection of tumors in the posterior
      hippocampus and the parahippocampal gyrus. By allowing the neurosurgeon to avoid
      unnecessary brain resection and retraction, this approach reduces the risk of
      injury to important lateral temporal and occipital lobe cortex and tracts. In
      addition, the resection of a posterior hippocampus or parahippocampal gyrus mass
      with the OST approach relieves temporal horn entrapment. Computer-assisted
      volumetric stereotaxy helps the neurosurgeon to maintain precise spatial and
      anatomic orientation and accurately delineates the margin between the tumor and
      the surrounding neural tissue.

PMID- 11950401
TI  - Natural history of tethered cord in patients with meningomyelocele.
AB  - OBJECTIVE: The purpose of this study was to describe the natural history of
      tethered cord in patients who have undergone meningomyelocele repair. METHODS: We
      performed a retrospective review of 45 patients with a history of neonatal
      meningomyelocele repair who subsequently developed symptoms of tethered cord.
      Symptoms of tethered cord in this cohort consisted of the development of bladder
      spasticity or orthopedic foot deformity. None of these patients were treated with
      cord untethering; instead, they were treated symptomatically. RESULTS: On follow
      up, 40 (88.9%) of these patients subsequently required additional orthopedic or
      urological procedures because of further symptoms of tethered cord. The incidence
      of progression of tethered cord syndrome is 27.5, 40, and 60% at 1, 2, and 5
      years, respectively. CONCLUSION: Although this study does not address the
      question whether cord untethering will prevent further symptom development, these
      results do provide a strong rationale for consideration of an untethering
      procedure in patients with repaired meningomyelocele at the time of the onset of
      symptoms of tethered cord.

PMID- 11950402
TI  - Clinical utility of quantitative cerebral blood flow measurements during internal
      carotid artery test occlusions.
AB  - OBJECTIVE: Internal carotid artery (ICA) balloon test occlusions (BTOs) are
      performed in the angiography suite to predict whether the patient has adequate
      collateral circulation to prevent stroke when permanent ICA occlusion (PCO) is
      required for treatment. Although many criteria have been proposed to facilitate
      predictions of stroke risk after PCO, no BTO techniques have been subjected to
      predictive validity testing in outcome studies. We describe a prospective case
      series study that tests the predictive validity of quantitative cerebral blood
      flow (CBF) measurements during ICA BTO. METHODS: Thirty-three patients with
      clinical indications for PCO underwent ICA BTO and then PCO. During BTO, standard
      neurological examinations, sustained-attention testing, and quantitative CBF
      measurements were performed. Two scalp scintillation detectors recorded washout
      data after ipsilateral intracarotid injection of xenon-133 through a port at the
      tip of the ICA-occluding balloon. Patients were monitored for the outcome measure
      of ipsilateral stroke for a mean of 34 months. The variables of quantitative CBF
      values, neurological examination results, sustained-attention test results, age,
      sex, and side of occlusion were examined with Kaplan-Meier log-rank tests,
      predictive validity analyses, and logistic regression analyses. RESULTS: CBF of
      less than 30 ml/100 g/min during BTO was the only variable that predicted stroke
      after PCO (log rank = 5.87, P = 0.015). The negative and positive predictive
      values for CBF findings were superior to those for standard neurological
      examination findings and sustained-attention test results. Age, sex, and side of
      occlusion did not predict stroke. CONCLUSION: Quantitative CBF testing, via the
      intracarotid injection technique, during BTO seems to be an important predictor
      of stroke after PCO.

PMID- 11950403
TI  - Effect of intraventricular sodium nitroprusside on cerebral hemodynamics and
      oxygenation in poor-grade aneurysm patients with severe, medically refractory
      vasospasm.
AB  - OBJECTIVE: Sodium nitroprusside (SNP) was recently suggested as a treatment for
      cerebral ischemia in patients with severe, medically refractory vasospasm after
      subarachnoid hemorrhage. In this study, we sought to objectify the effect on
      cerebral hemodynamics and oxygenation (PbrO2) when using intraventricular SNP as
      a last resort therapy in poor-grade patients with subarachnoid hemorrhage;
      severe, medically refractory vasospasm; and compromised cerebral blood flow.
      METHODS: Thirteen of 185 consecutive patients with subarachnoid hemorrhage
      developed severe, medically refractory vasospasm and were treated with
      intraventricular SNP. All of these patients' neurological conditions were
      classified as Hunt and Hess Grade IV. SNP doses ranged from 10 to 40 mg with
      single-dose treatment and from 2 to 8 mg/h with continuous infusion. Angiography
      or PbrO2 measurement was used to assess the treatment effects. RESULTS: In 6 of
      the 13 patients, SNP improved cerebral hemodynamics, as demonstrated by increased
      PbrO2 or decreased cerebral circulation time. Only 1 patient showed increased
      diameter of the spastic vessel, however. Maximum increase in PbrO2 ranged from 5
      to 52 mmHg. Adverse effects were hypertension in five patients, vomiting in three
      patients, and cardiac arrhythmia in one patient. Cerebral infarctions caused by
      vasospasm occurred in 6 (46%) of the 13 patients. No differences between SNP
      responders and SNP nonresponders were noted. CONCLUSION: In patients with severe,
      medically refractory vasospasm, intraventricular SNP may improve PbrO2 and
      cerebral blood flow, but the effect is highly variable. On the basis of the
      improvements we observed in 6 of 13 patients, intraventricular SNP administration
      is justified as a last resort therapy in patients with cerebral ischemia and
      impending infarction. Our findings suggest that SNP may be more effective when
      initiated early and administered continuously.

PMID- 11950404
TI  - Prognosis and prognostic factors for unexplained subarachnoid hemorrhage: review
      of 84 cases.
AB  - OBJECTIVE: We conducted a retrospective study to investigate the prognosis,
      possible prognostic factors, and long-term natural history of subarachnoid
      hemorrhage of unexplained cause. METHODS: This report contains a retrospective
      analysis of data for 84 patients with subarachnoid hemorrhage of unknown cause
      who were monitored for 1 month to 9.5 years, with an average follow-up period of
      5.6 years. We evaluated the associations between computed tomographic (CT) scan
      features, clinical grade, loss of consciousness during hemorrhage, ventricular
      ratio, angiographic spasm, complications (such as death resulting from ischemia,
      early rebleeding, late rebleeding, epilepsy, hydrocephalus, and fixed ischemic
      deficits), and outcomes, using a nonparametric, two-sample, Kolmogorov-Smirnov
      test. The chi2 test was used to test the independence of two categorical
      variables. RESULTS: CT class exhibited a significant association with clinical
      grade (gamma = 0.865, P = 0.006), loss of consciousness during hemorrhage (gamma
      = 0.69, P = 0.001), and ventricular ratio (gamma = 0.8175, P = 0.01) but a
      nonsignificant association with angiographic vasospasm (gamma = 0.21, P = 0.2).
      Death resulting from ischemic complications and fixed ischemic deficits were
      strongly associated with clinical grade (P = 0.003 and P = 0.008, respectively)
      but weakly associated with CT class (P = 0.06 and P = 0.084, respectively).
      Angiographic vasospasm was strongly associated only with fixed ischemic deficits
      among complications (P = 0.001). Clinical outcome was strongly positively
      associated with CT class (gamma = 0.685, P = 0.001), clinical grade (gamma =
      0.81, P = 0.001), and ventricular ratio (gamma = 0.57, P = 0.002) but weakly
      positively associated with loss of consciousness during hemorrhage (gamma =
      0.459, P = 0.0487) and angiographic vasospasm (gamma = 0.48, P = 0.04).
      CONCLUSION: Our study confirms earlier studies reporting a good prognosis for
      survival, but it does not confirm the earlier statements regarding low morbidity
      rates. Although clinical grade and the presence and amount of subarachnoid blood
      on CT scans are the major prognostic factors related to the incidence of ischemic
      complications, clinical grade and CT class are also the main parameters, with
      ventricular ratio, indicating clinical outcomes for patients with subarachnoid
      hemorrhage of unknown cause.

PMID- 11950405
TI  - Detection of microemboli by transcranial Doppler ultrasonography in aneurysmal
      subarachnoid hemorrhage.
AB  - OBJECTIVE: To determine the frequency and characteristics of microembolic signals
      (MES) in subarachnoid hemorrhage (SAH). METHODS: Twenty-three patients with
      aneurysmal SAH were monitored with transcranial Doppler ultrasonography for the
      presence of MES and vasospasm. Each middle cerebral artery was monitored for 30
      minutes three times each week. Patients were excluded if they had traumatic SAH
      or cardiac or arterial sources of emboli. Monitoring was initiated 6.3 days (1-16
      d) after SAH and lasted 6.6 days (1-13 d). Eleven individuals without SAH or
      other cerebrovascular diseases who were treated in the same unit served as
      control subjects. Each patient underwent monitoring of both middle cerebral
      arteries a mean of three times; therefore, 46 vessels were studied (a total of
      138 observations). Control subjects underwent assessment of each middle cerebral
      artery once, for a total of 22 control vessels. RESULTS: MES were detected for 16
      of 23 patients (70%) and 44 of 138 patient vessels (32%) monitored, compared with
      2 of 11 control subjects (18%) and 2 of 22 control vessels (9%) (P < 0.05). MES
      were observed for 83% of patients with clinical vasospasm and 54% of those
      without clinical vasospasm. Ultrasonographic vasospasm was observed for 71 of 138
      vessels monitored; MES were observed for 28% of vessels with vasospasm and 36% of
      those without vasospasm. Aneurysms proximal to the monitored artery were
      identified in 38 of 138 vessels, of which 34% exhibited MES, which is similar to
      the frequency for vessels without proximal aneurysms (31%). Coiled, clipped, and
      unsecured aneurysms exhibited similar frequencies of MES. CONCLUSION: MES were
      common in SAH, occurring in 70% of cases of SAH and one-third of all vessels
      monitored. Although MES were more frequent among patients with clinical
      vasospasm, this difference did not reach statistical significance. We were unable
      to demonstrate a relationship between ultrasonographic vasospasm and MES, and the
      presence of a proximal secured or unsecured aneurysm did not alter the chance of
      detection of MES. Further studies are required to determine the origin and
      clinical relevance of MES in SAH.

PMID- 11950407
TI  - Magnetic resonance imaging-guided stereotactic limbic leukotomy for treatment of
      intractable psychiatric disease.
AB  - OBJECTIVE: To assess the efficacy and complication rates of magnetic resonance
      imaging-guided stereotactic limbic leukotomy for the treatment of intractable
      major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). METHODS:
      We conducted preoperative evaluations and postoperative follow-up assessments of
      efficacy and complications for 21 patients who underwent limbic leukotomy.
      Efficacy was based on physician- and patient-rated global assessments of
      functioning, as well as evaluations using disease-specific rating scales commonly
      used in studies of MDD and OCD. RESULTS: The mean time from limbic leukotomy to
      follow-up assessment was 26 months. On the basis of standard outcome measures, 36
      to 50% of patients were considered to be treatment responders. Although permanent
      surgical morbidity was rare, there were reports of postoperative sequelae,
      including apathy, urinary incontinence, and memory complaints, which occurred in
      a substantial minority of cases. CONCLUSION: For this cohort of 21 patients with
      chronic severe MDD or OCD, who had experienced failure with an exhaustive array
      of previous treatments, limbic leukotomy was associated with substantial benefit
      for 36 to 50%. This rate is comparable to those of previous studies of limbic
      system surgery and indicates that limbic leukotomy is a feasible treatment option
      for severe, treatment-refractory MDD or OCD. Adverse consequences associated with
      the procedure included affective, cognitive, and visceromotor sequelae, which
      were generally transient.

PMID- 11950406
TI  - Immediate neurocognitive effects of concussion.
AB  - OBJECTIVE: To prospectively measure the immediate neurocognitive effects and
      early course of recovery from concussion and to examine the effects of loss of
      consciousness (LOC) and posttraumatic amnesia (PTA) on the severity of
      neurocognitive impairment immediately after concussion. METHODS: A sports-related
      concussion research model was used to allow prospective immediate evaluation of
      concussion. A total of 2385 high school and college football players were
      studied. Ninety-one players (3.8%) sustained concussions during the study. A
      brief neurocognitive and neurological screening measure, the Standardized
      Assessment of Concussion, was used to assess cognitive functioning before the
      football season, immediately after injury, and 15 minutes, 48 hours, and 90 days
      after injury. RESULTS: Standardized Assessment of Concussion scores immediately
      after concussion were significantly lower than the preseason baseline score and
      the noninjured population baseline mean, even for injured subjects without LOC or
      PTA. Subjects with LOC were most severely impaired immediately after injury,
      whereas those without LOC or PTA were least impaired. Significant impairment was
      also detected 15 minutes after injury, but all three groups returned to baseline
      levels of cognitive functioning within 48 hours. CONCLUSION: These findings are
      the first to demonstrate not only that a gradient of increasing concussion
      severity is represented by PTA and LOC but also that measurable neurocognitive
      abnormalities are evident immediately after injury without PTA or LOC.

PMID- 11950408
TI  - Evaluation of preoperative administration of the cyclooxygenase-2 inhibitor
      rofecoxib for the treatment of postoperative pain after lumbar disc surgery.
AB  - OBJECTIVE: A combination of analgesics with different mechanisms of action may
      improve postoperative pain control and reduce the incidence of side effects. This
      study was designed to assess the efficacy of preoperative administration of
      rofecoxib (Vioxx; Merck & Co., Inc., Somerset, NJ) in reducing pain and opioid
      requirements after single-level lumbar microdiscectomy. METHODS: A randomized,
      double-blind, placebo-controlled clinical trial was performed on 61 consenting
      patients who were considered American Society of Anesthesiologists Class I or II
      and who were scheduled for elective single-level lumbar microdiscectomy. Patients
      received either two doses of rofecoxib 50 mg or a placebo preoperatively. The
      outcome measures included morphine use in the postanesthesia care unit (PACU),
      discharge times, and side effect profile. Data were analyzed by use of
      independent sample t tests for continuous variables or chi(2) tests for
      categorical variables. A P value of <0.05 was considered significant. RESULTS:
      The two groups were comparable with respect to patient characteristics,
      intraoperative opioid and hypnotic consumption, and duration of surgery. Patients
      in the rofecoxib group required significantly less morphine postoperatively.
      Significantly more patients in the placebo group reported pain scores greater
      than 7 at admission to the PACU. Time to first request for analgesia was shorter
      in the placebo group, but the difference did not reach statistical significance.
      There were no significant differences between groups in the incidence of nausea,
      time to discharge from the PACU, or hospital stay. CONCLUSION: Preoperative
      rofecoxib is effective in reducing postoperative narcotic consumption in patients
      undergoing lumbar laminectomy. The use of rofecoxib does not shorten PACU length
      of stay or hospital discharge time. These outcome measures depend on multiple
      administrative factors.

PMID- 11950409
TI  - Intrinsic spinal cord tumor resection.
AB  - SPINAL CORD TUMORS are more frequently detected than in the past, because of
      progress in neuroradiology. Many neurosurgeons must now decide how to treat such
      lesions. The recent neurosurgical literature contains many case reports, few
      series, and different strategies. This article describes the surgical method I
      have developed in a period of 15 years, with Georges Fischer in Lyon, on the
      basis of experience with more than 260 patients and 300 operations. The standard
      treatment is complete resection whenever possible, but we must learn when and
      where to stop to preserve the quality of life. I have several useful strategies,
      which are explained in this report. For gliomas (ependymomas and astrocytomas), I
      favor a midline approach; for most vascular tumors (such as hemangioblastomas and
      cavernomas), however, I prefer to proceed from the point at which the lesion is
      observed through the microscope and to dissect the lesion in one piece.
      Meticulous nonbleeding surgery and experience are the keys to success.

PMID- 11950410
TI  - Assessment of human brain water content by cerebral bioelectrical impedance
      analysis: a new technique and its application to cerebral pathological
      conditions.
AB  - OBJECTIVE: Total brain water content changes in several cerebral pathological
      conditions and the measurement of brain water content are important for the
      selection of appropriate therapeutic procedures. We present a quantitative, in
      vivo, bioelectrical impedance analysis (BIA) method and propose its use for the
      accurate assessment of brain water content among human subjects. METHODS:
      Cerebral BIA is based on the conduction of an applied current in the brain
      parenchyma. Application of an excitatory current of 800 microA at 50 kHz, via two
      electrodes placed on the eyelids with the eyes closed, and detection of the
      voltage drop with two electrodes placed in the suboccipital region allow brain
      resistance and reactance to be measured. By means of an equation that considers
      cranial circumference and resistance, it is possible to quantify the total brain
      water content, expressed as the bioelectrical volume. Cerebral BIA was performed
      with a series of healthy volunteers (n = 100), for determination of average brain
      water content values. The method was then applied to 50 patients with brain
      tumors (n = 20), intracranial hemorrhage (n = 16), or hydrocephalus (n = 14), for
      assessment of changes in global brain water contents. Data were compared with
      those obtained for healthy volunteers. RESULTS: Statistically significant
      differences (P < 0.001) were observed between the two groups. Mean brain water
      content values (expressed as bioelectrical volume values) were 38.2 +/- 3.9
      cm2/Omega for healthy volunteers and 67.7 +/- 13.1 cm2/Omega for patients with
      cerebral pathological conditions. Statistically significant differences (P <
      0.05) were also observed among patients with cerebral pathological conditions.
      CONCLUSION: The results of this study suggest that BIA, applied to the cerebral
      parenchyma, is a valid method for the prediction of brain water contents under
      both normal and pathological conditions. However, further studies are needed to
      establish whether it is sensitive and reliable enough for future clinical
      applications.

PMID- 11950411
TI  - Graded contusion model of the mouse spinal cord using a pneumatic impact device.
AB  - OBJECTIVE: This study examined the effects of varying magnitudes of controlled
      spinal cord impact to the mouse spinal cord on neurological and histopathological
      variables to obtain a mouse model of spinal cord injury (SCI). METHODS: A
      laminectomy of the T10 vertebra was performed on anesthetized C57BL/6 mice. A
      pneumatic pressure-driven impact was performed on the spinal cord through the
      dura mater. Experimental groups were subdivided according to the energy of impact
      (0.25-mm-deep deformations): Group 1 (n = 5), impact velocity at 1 m/s; Group 2
      (n = 5), impact velocity at 2 m/s; and Group 3 (n = 5), impact velocity at 3 m/s.
      Functional deficits over time were evaluated up to 28 days after SCI by testing
      hindlimb reflex and coordinated motor function. The extent of the lesions was
      analyzed histopathologically and quantified by a morphometric measurement.
      RESULTS: Mice of all groups exhibited profound functional deficits immediately
      after injury and subsequent gradual symptomatic recovery. The degrees of recovery
      were precisely correlated with the magnitudes of impact. The extent of resultant
      cord lesions was highly reproducible among animals, with little variance: means
      +/- standard deviation, 0.86 +/- 0.06/100 mm3 in Group 1; 2.4 +/- 0.28/100 mm3 in
      Group 2; and 11.0 +/- 1.0/100 mm3 in Group 3. CONCLUSION: Our results indicate
      that this model provides constant functional and histopathological lesions
      according to impact energy. This new mouse model of SCI opens a new avenue for
      studies investigating roles and/or effects of specific genes in the recovery
      process of SCI.

PMID- 11950412
TI  - Up-regulation of parathyroid hormone receptor in cerebral arteries after
      subarachnoid hemorrhage in monkeys.
AB  - OBJECTIVE: Complementary deoxyribonucleic acid array analysis was used to
      determine whether vasospasm after subarachnoid hemorrhage (SAH) is associated
      with changes in gene expression. METHODS: Right SAHs were created in three
      monkeys, and the right and left middle cerebral arteries were collected 3, 7, or
      14 days after SAH. Vasospasm was assessed by angiography performed on Day 0 and
      at tissue harvest. A complementary deoxyribonucleic acid array containing 5184
      genes was used to screen for changes in gene expression by comparing the right
      and left middle cerebral arteries. RESULTS: There was significant expression
      (greater than fivefold expression of messenger ribonucleic acid compared with
      internal standard control) of 537 genes (10%) in the middle cerebral arteries.
      One hundred sixty-four genes (31%) did not change significantly, and 373 (69%)
      were differentially expressed at 3, 7, or 14 days after SAH. These 373 genes
      changed from 1.2- to 7-fold as compared with control arteries. The most common
      pattern was a progressive increase with increased time after SAH. The functions
      of differentially expressed genes included the regulation of gene expression,
      cell proliferation, inflammation, membrane proteins and receptors, kinases, and
      phosphatases. There was a marked increase in parathyroid hormone and parathyroid
      hormone receptor with time after SAH. Immunoblotting demonstrated a significant
      increase in parathyroid hormone receptor protein. CONCLUSION: The up-regulation
      of these proteins involved in vascular relaxation suggests that they may play a
      role in vasospasm. The progressive increase in messenger ribonucleic acids
      involved in the functions noted suggests that the pathogenesis of cerebral
      vasospasm involves cell proliferation, inflammation, and possibly smooth muscle
      phenotype change.

PMID- 11950413
TI  - Human brain tumor cell culture characterization after immunostimulatory gene
      transfer.
AB  - OBJECTIVE: Immunogene therapy is a novel cancer treatment strategy based on
      vaccination with irradiated autologous tumor cells transduced with
      immunostimulatory genes. To characterize such cells before clinical applications,
      we studied a human glioma cell line (D54 MG) and early passage human glioma
      (Ed147.BT, Ed149.BT) and melanoma (Ed141.MEL) cultures after immunostimulatory
      gene transfer. METHODS: Granulocyte-macrophage colony-stimulating factor (GM
      CSF), interleukin-12 (IL-12), and B7-2 genes were retrovirally transferred to
      tumor cells. Gene expression before and after irradiation (200 Gy) was assessed
      by enzyme-linked immunosorbent assay (GM-CSF, IL-12) and flow cytometry (B7-2).
      Viability and clonogenicity were determined via trypan blue staining before and
      after irradiation. Growth rates were determined by serial cell counts. RESULTS:
      GM-CSF expression was high in GM-CSF-transduced (10.36-162.10 ng/10(6) cells/d
      preirradiation and 10.22-122.02 ng/10(6) cells/d postirradiation) but lower in B7
      2/GM-CSF-transduced cultures (1.41-2.90 ng/10(6) cells/d preirradiation, 1.96
      5.02 ng/10(6) cells/d postirradiation). IL-12 expression also was lower (1.30
      2.10 ng/10(6) cells/d preirradiation, 0.47-1.70 ng/10(6) cells/d
      postirradiation). B7-2 expression was high (one- to two-logarithm increase in
      fluorescence) and unaffected by radiation. Postirradiation viability was
      initially high (94.20 +/- 8.46%, Day 1) but decreased rapidly (28.13 +/- 4.64%,
      Day 10). No cultures demonstrated evidence of clonogenicity (i.e., cell division)
      after 200-Gy irradiation. Growth rates were similar in wild-type and gene
      transduced Ed141.MEL, Ed147.BT, and Ed149.BT. However, D54MG-IL-12 growth was
      slower than that of wild-type D54MG. CONCLUSION: GM-CSF, IL-12, and B7-2 genes
      can be transferred to human glioma and melanoma cell cultures efficiently by use
      of our retroviral vectors. Irradiation (200 Gy) does not significantly alter
      therapeutic gene expression. Irradiated cells remain viable for several days but
      cannot undergo further cell division. Early passage culture growth rates are not
      altered by therapeutic gene expression but are decreased by IL-12 in an
      immortalized cell line (D54MG). These results suggest that it is feasible to
      create vaccines with irradiated, autologous, genetically modified brain tumor
      cells.

PMID- 11950414
TI  - Neurosurgical training in the United kingdom and ireland: assessing progress and
      attainment.
AB  - OBJECTIVE: To review neurosurgical training in the United Kingdom and Ireland in
      the past decade and the methods used to monitor training and assess trainee
      competence. METHODS: A database was compiled with data from 1990 to 2000 on
      behalf of the Specialist Advisory Committee in Neurosurgery from trainee logbook
      operative totals submitted on achieving accreditation or receiving the
      Certificate of Completion of Surgical Training. RESULTS: During the 11-year
      period, 109 trainees achieved accreditation or Certificate of Completion of
      Surgical Training. The median duration of training, including research, was 6.1
      years. The total training duration per year did not change overall, although
      results suggested an increasing trend in the duration of clinical training
      (excluding research) from 4.8 to 5.6 years since 1997. The median age at
      accreditation or at receipt of Certificate of Completion of Surgical Training was
      35 years 7 months. At completion of training, the Specialist Advisory Committee
      used operative totals in addition to reports from trainers to analyze the
      trainees' competence. Despite changes to the training system and a reduction in
      hours of work, the quality of training, as reflected by median operative totals,
      did not change during the decade. The database also permitted assessment of
      operative experience gained within each training program. CONCLUSION: The
      duration of training and training standards in terms of operative experience have
      remained constant during the past decade. Operative totals provide an objective
      method of assessing trainee progress and attainment and enable a comparison of
      experience offered by different training programs. An alternative method of
      assessing trainee operative competence that can be used in conjunction with
      median operative totals is proposed.

PMID- 11950415
TI  - Surgical indications and microsurgical anatomy of the transchoroidal fissure
      approach for lesions in and around the ambient cistern.
AB  - OBJECTIVE: Opening the temporal part of the choroidal fissure (CF) makes it
      possible to expose the crural cistern, the ambient cistern, and the medial
      temporal lobe. We examined the microsurgical anatomy and the surgical indications
      for use of the trans-CF approach. METHODS: The microsurgical anatomy encountered
      in the trans-CF approach for lesions in and around the ambient cistern was
      studied in three cadavers. On the basis of these cadaveric studies, the trans-CF
      approach was used during surgery in three live patients with such lesions.
      RESULTS: The angiographic "plexal point," which indicates the entrance of the
      anterior choroidal artery as it enters the temporal horn of the lateral
      ventricle, was thought to be a key anatomic landmark of the trans-CF approach. A
      cortical incision for entry into the temporal horn should be made in the inferior
      temporal gyrus to minimize the potential damage to the optic radiations and to
      the speech centers. After the CF is opened posteriorly to the plexal point
      between the tenia fimbria and the choroid plexus, the posterior cerebral artery
      (PCA) in the ambient cistern can be observed with minimal caudal retraction of
      the hippocampus. In this study, surgical procedures using the trans-CF approach
      were successfully performed on patients with high-positioned P2 aneurysms whose
      PCA ran close to the plexal point or higher, whose medial temporal arteriovenous
      malformations were fed mainly by the PCA, and whose tentorial hiatus meningiomas
      protruded into the temporal horn through the CF, with no resulting postoperative
      visual or memory disturbances. CONCLUSION: The trans-CF approach is especially
      useful in surgery for lesions in and around the ambient cistern.

PMID- 11950416
TI  - History of the Lahey Clinic department of neurosurgery.
AB  - THIS HISTORY OF one of the early departments of neurosurgery provides some
      perspective on the changing practice of this specialty during its formative
      years. Under the guidance of James L. Poppen and Gilbert Horrax, the Department
      of Neurosurgery at the Lahey Clinic assumed a prominent role in extending Harvey
      Cushing's methods, enlightened by Poppen's techniques, many of which were ahead
      of their time, and provided inspiration to the next generations of neurosurgeons.
      Although the pattern of neurosurgery has changed remarkably in the past 70 years,
      basic principles have remained much the same.

PMID- 11950417
TI  - Visual field deficit caused by vascular compression from a suprasellar
      meningioma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Suprasellar meningiomas typically cause bitemporal
      hemianopsia by direct compression of the chiasm, its blood supply, or both. We
      report another mechanism for visual loss in suprasellar meningiomas, whereby
      compression by the suprajacent vascular complex is the offending agent. CLINICAL
      PRESENTATION: A 78-year-old woman with a suprasellar meningioma was diagnosed
      incidentally. During the follow-up period, she developed an inferior homonymous
      wedge defect consistent with superior compression, without any detectable
      radiological progression. It was decided to resect her tumor. INTERVENTION: The
      patient underwent a fronto-orbital approach for tumoral excision.
      Intraoperatively, a groove by the anterior cerebral artery complex was found
      along the superior surface of the chiasm. Postoperatively, the patient's visual
      deficit resolved. CONCLUSION: This case illustrates an unusual visual field
      deficit associated with a suprasellar meningioma. It also emphasizes the
      importance of frequent and careful visual field monitoring, which can precede
      radiological and symptomatic progression.

PMID- 11950418
TI  - Ganglioglioma presenting as a meningioma: case report and review of the
      literature.
AB  - OBJECTIVE AND IMPORTANCE: Gangliogliomas are intra-axial, avascular masses
      located predominantly in the temporal lobe. A ganglioglioma that mimics a
      meningioma in that it is extra-axial and has a significant extracranial vascular
      supply has not been reported previously. CLINICAL PRESENTATION: A 12-year-old
      girl presented with a right temporoparietal mass. A neurological examination
      revealed nothing abnormal, and the girl's symptoms were limited to headaches.
      INTERVENTION: Magnetic resonance imaging revealed an extra-axial mass, and
      cerebral catheter angiography revealed a blood supply mainly from the posterior
      division of the right middle meningeal artery. Intraoperative findings confirmed
      the extra-axial location of the tumor, and histological analysis revealed that
      the tumor was a ganglioglioma. CONCLUSION: This report confirms that
      gangliogliomas can present as extra-axial, vascular masses that are similar to
      meningiomas.

PMID- 11950419
TI  - De novo cerebral arteriovenous malformation: case report.
AB  - OBJECTIVE AND IMPORTANCE: Arteriovenous malformations (AVMs) are generally
      thought to have a congenital cause. This is the first report of an
      angiographically proven de novo cerebral AVM in an adult patient without previous
      vascular abnormality. CLINICAL PRESENTATION: A 26-year-old African-American woman
      developed multiple cranial nerve deficits and ataxia over the course of a few
      days after a streptococcal throat infection. T2-weighted magnetic resonance
      imaging scans revealed a hyperintense signal in the midbrain with extension into
      the diencephalon. A cerebral angiogram performed at that time to exclude
      vasculitis revealed normal cerebral vasculature. The patient was treated with
      corticosteroids, and symptoms resolved. Subsequently, at the age of 32, this
      patient presented with a severe headache and emesis, but with no focal
      neurological deficit. INTERVENTION: The patient's cranial computed tomographic
      and magnetic resonance imaging scans revealed a right posterior temporal
      intraparenchymal hemorrhage, and cerebral angiography revealed a new 3- by 2-cm
      AVM. The patient underwent microsurgical resection of the AVM and associated
      hematoma. Postoperative angiography revealed no evidence of residual AVM.
      CONCLUSION: This study details the case of a woman who developed a de novo
      cerebral AVM during a 6-year period. This report challenges the conventional
      belief that all AVMs have a congenital cause.

PMID- 11950420
TI  - Spontaneous thrombosis of a residual arteriovenous malformation in eloquent
      cortex after surgery: case report.
AB  - OBJECTIVE AND IMPORTANCE: The presence of a residual arteriovenous malformation
      (AVM) on postoperative angiograms is typically an indication for prompt return to
      the operating room to complete resection, because of the risk of early
      hemorrhage. This approach, however, may involve risks of neurological deficits
      when the residual AVM is in eloquent cortex. We present a case of complete
      thrombosis of a residual AVM after surgery. This residual AVM tissue was located
      in eloquent cortex. Complete spontaneous thrombosis of residual AVMs after
      surgery has only rarely been reported. This phenomenon raises questions regarding
      the most appropriate management for residual AVMs in eloquent cortex. CLINICAL
      PRESENTATION: The patient was a 43-year-old, right-handed, male patient with an
      AVM centered in the left precentral gyrus. The patient presented with medically
      intractable seizures and progressive right hemiparesis. After AVM resection,
      angiography revealed a residual AVM with early venous drainage. Angiography
      performed 1 week later demonstrated a persisting AVM nidus without early venous
      drainage. Angiography performed 3 months later demonstrated complete thrombosis
      of the residual AVM. INTERVENTION: The patient has been monitored for more than 1
      year, without additional symptoms or therapy. CONCLUSION: We continue to advocate
      prompt return to the operating room when postoperative angiography reveals a
      residual AVM with persistent shunting. When the residual AVM is in eloquent
      cortex and is small, with a single draining vein, however, observation of the
      patient (with strict blood pressure control) and repeat angiography after 1 week
      represent an alternative strategy that is supported by this case report. As this
      case demonstrates, it is possible for small residual AVMs to thrombose. This may
      avert the need for reoperation for residual AVMs in eloquent cortex, with the
      potential for neurological deficits.

PMID- 11950421
TI  - Fatal subarachnoid hemorrhage, with brainstem and cerebellar infarction, caused
      by Aspergillus infection after cerebral aneurysm surgery: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intracranial aspergillosis has been reported to cause
      subarachnoid hemorrhage (SAH) attributable to ruptured mycotic aneurysms. We
      describe a case of Aspergillus arteritis that caused SAH without aneurysm
      formation, followed by successive brainstem and cerebellar infarction. CLINICAL
      PRESENTATION: A 50-year-old woman experienced a sudden onset of headache.
      Computed tomography demonstrated SAH. After angiography revealed an aneurysm of
      the anterior communicating artery, a complete neck-clipping operation was
      performed, without neurological deterioration. However, the patient experienced
      another episode of SAH on the 26th postoperative day. INTERVENTION: We repeated
      the craniotomy and confirmed that the clip was still intact. A second
      angiographic evaluation did not reveal an aneurysm or any other cause of
      hemorrhage. On the 30th postoperative day, magnetic resonance imaging
      demonstrated cerebellar infarction in the territory of the anteroinferior
      cerebellar artery. The patient died on the 40th postoperative day, after another
      episode of SAH and progressive cerebellar and brainstem infarction. The
      postmortem examination revealed destruction of the basilar artery and occlusion
      of the basilar and vertebral arteries attributable to Aspergillus arteritis.
      CONCLUSION: When a patient presents with SAH of unknown origin followed by
      cerebral infarction, Aspergillus arteritis should be included in the differential
      diagnosis. Earlier recognition of this fungal infection improves the prognosis.

PMID- 11950422
TI  - Prenatal diagnosis of terminal myelocystocele in the fetal surgery era: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: We report a case of a child with terminal
      myelocystocele (TMC). This case exemplifies the importance of performing a
      multidisciplinary evaluation and magnetic resonance imaging in the patient with
      suspected meningomyelocele when fetal surgery is being considered. CLINICAL
      PRESENTATION: This patient was evaluated at the Center for Fetal Diagnosis and
      Treatment and considered for fetal surgery to repair meningomyelocele. TECHNIQUE:
      A follow-up based on both ultrasound and magnetic resonance imaging was performed
      throughout pregnancy. CONCLUSION: Although a definitive diagnosis of TMC was not
      established prenatally, the patient was not offered fetal surgery, based on
      multiple selection criteria. We correlate the pathophysiology of TMC with the
      radiographic and amniocentesis findings. TMC must be considered in the
      differential diagnosis in a fetus with a dysraphic defect.

PMID- 11950423
TI  - Cranial base approaches for the surgical treatment of aggressive posterior fossa
      dural arteriovenous fistulae with leptomeningeal drainage: report of four
      technical cases.
AB  - OBJECTIVE AND IMPORTANCE: Dural arteriovenous fistulae (DAVFs) with
      leptomeningeal drainage have an aggressive natural history. Urgent treatment is
      necessary to arrest neurological deterioration and to prevent the risk of
      intracranial hemorrhage. In many patients, a primary endovascular approach is the
      most appropriate and most successful treatment available. In some circumstances,
      however, surgical intervention is required for complete obliteration. Posterior
      fossa DAVFs are generally deep-seated and difficult to gain access to with
      standard surgical approaches. The advent of cranial base surgery allows 360
      degree access to the draining venous complex or sinus via extradural bone
      removal. CLINICAL PRESENTATION: Four patients with posterior fossa DAVFs
      presented to the neurosurgical service at our institutions. One DAVF was located
      at the craniocervical junction, and three were tentorial DAVFs of the superior
      petrosal sinus. All four patients were treated surgically with extradural bone
      removal. INTERVENTION: Postoperative angiography documented complete obliteration
      of all four DAVFs. All patients had normal recoveries, with the exception of one
      patient who experienced persistent temporal lobe seizure activity as a result of
      the presenting hematoma. One patient died of unrelated causes 2 years after
      surgery. One postoperative temporal lobe hematoma required evacuation.
      CONCLUSION: Recent advances in cranial base techniques have allowed the
      successful obliteration of aggressive posterior fossa DAVFs with acceptable
      morbidity. The use of these techniques should be considered in selected patients
      who cannot be treated with endovascular approaches.

PMID- 11950424
TI  - Breakage of the cranial pinholder of the Patil stereotactic system.

PMID- 11950425
TI  - Relation of markers of inflammation (C-reactive protein, fibrinogen, von
      Willebrand factor, and leukocyte count) and statin therapy to long-term mortality
      in patients with angiographically proven coronary artery disease.
AB  - We evaluated a possible interaction between statins and inflammation in 1,246
      patients with angiographically diagnosed coronary artery disease. Four different
      inflammatory markers were determined: high, sensitive C-reactive protein (hs-CRP)
      (p = 0.001), fibrinogen (p = 0.006), von Willebrand factor (p = 0.006), and
      leukocyte count (p = 0.03); these levels were significantly higher among the 88
      patients who died of cardiac causes during follow-up (median 2.9 years) than
      among survivors. In a multivariate backward stepwise Cox regression mode, only hs
      CRP was evaluated to be a significant predictor of death from coronary artery
      disease. This prediction was lost in statin-treated patients. Compared with
      patients receiving statin medication, patients without statins did not have
      increased cardiac mortality (even when low-density lipoprotein [LDL] levels were
      >125 mg/dl) when hs-CRP levels were not elevated. In contrast, patients without
      statins and elevated hs-CRP (top quartile) had a 2.3-fold increase in risk for
      fatal coronary events, independent of LDL levels. In conclusion, only elevated hs
      CRP was selected as an independent predictor of death. Statin therapy is
      associated with elevated hs-CRP, with a risk reduction for fatal coronary events,
      independent of LDL levels; this, in part, may be explained by the anti
      inflammatory effects on atherosclerosis.

PMID- 11950427
TI  - Usefulness of multislice computed tomography for detecting obstructive coronary
      artery disease.
AB  - The latest generation of multislice spiral computed tomography (MSCT) scanners is
      capable of noninvasive coronary angiography. We evaluated its diagnostic accuracy
      to detect stenotic coronary artery disease (CAD). In 53 patients with suspected
      CAD, contrast-enhanced MSCT and conventional angiography were performed. The CT
      data were acquired within a single breathhold, and isocardiophasic slices were
      reconstructed by means of retrospective electrocardiographic gating. Coronary
      segments of > or = 2 mm in diameter, measured by quantitative angiography, were
      evaluated. In 70% of the 358 available segments, image quality was regarded as
      adequate for assessment. The overall sensitivity, specificity, and positive and
      negative predictive values to detect > or = 50% stenotic lesions in the
      assessable segments were 82% (42 of 51 lesions), 93% (285 of 307 nonstenotic
      segments), and 66% and 97%, respectively, regarding conventional quantitative
      angiography as the gold standard. Proximal segments were assessable in 92%, and
      distal segments and side branches in 71% and 50%, respectively. Including the
      undetected lesions in non-assessable segments, overall sensitivity decreased to
      61% but remained 82% for lesions in proximal coronary segments. MSCT correctly
      predicted absent, single, or multiple lesions in 55% of patients. Thus, despite
      potentially high image quality, current MSCT protocols offer only reasonable
      diagnostic accuracy in an unselected patient group with a high prevalence of CAD.

PMID- 11950426
TI  - Comparison of C-reactive protein and terminal complement complex in patients with
      unstable angina pectoris versus stable angina pectoris.
AB  - Elevated C-reactive protein (CRP) can identify patients with coronary artery
      disease who are prone to future acute events. We investigated whether elevated
      CRP is related to the activation of the terminal complement cascade in 66
      patients with unstable angina pectoris (UAP), in 45 patients with stable angina
      pectoris, and in 42 controls. CRP, additional acute phase reactants, the terminal
      complement complex (sC5b-9), leukocytes, and troponin T were measured. In 47
      patients with UAP the CRP values were regarded as elevated (>0.3 mg/dl). In
      patients with UAP and elevated CRP, the plasma levels of sC5b-9 were markedly
      higher than in patients with UAP and lower CRP (245 +/- 14 vs 188 +/- 19 ng/ml, p
      <0.02) and in patients with stable angina pectoris with slightly (0.4 +/- 0.1
      mg/dl) increased CRP (sC5b-9 173 +/- 21 vs 130 +/- 7 ng/ml [controls; p <0.05]).
      A further acute phase reaction was present only in patients with UAP and elevated
      CRP already on admission (p <0.01). sC5b-9 was not related to troponin release.
      Thus, elevated CRP levels are associated with activation of the plaque
      destabilizating terminal complement system in patients with UAP during the acute
      phase reaction. This may explain the prognostic value of CRP in acute coronary
      syndromes (ACS).

PMID- 11950428
TI  - Plasma homocysteine, methylenetetrahydrofolate reductase genotypes, and age at
      onset of symptoms of myocardial ischemia.
AB  - Elevated fasting plasma homocysteine is a graded risk factor of coronary artery
      disease (CAD) and may accelerate onset of CAD. Homozygosity for the C677T
      mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is commonly but
      inconsistently associated with hyperhomocysteinemia. In the present study we
      examined the possible relation between levels of fasting plasma homocysteine and
      age at CAD onset in different MTHFR genotypes. We studied 182 patients with CAD,
      74 patients with early onset CAD (aged < or = 45 years), and 108 patients with
      later onset CAD (aged 46 to 65 years). Plasma homocysteine levels in 90 subjects
      without CAD were used for control. Fasting plasma homocysteine levels in T/T
      homozygotes with early onset CAD (20.2 +/-12.5 micromol/L) was markedly higher
      than in T/T homozygotes with later onset CAD (13.4 +/- 6.8 micromol/L) and in
      patients with early onset CAD who were not T/T homozygotes (11.9 +/- 3.7
      micromol/L; p = 0.034 and p = 0.0001, respectively). CAD developed earlier in T/T
      homozygotes who were hyperhomocysteinemic (>15 micromol/L) than in the T/T
      homozygotes who were not (p = 0.036). Plasma homocysteine levels had no effect on
      age at onset of CAD in patients who were non-T/T genotypes. Homocysteine levels
      in control subjects and in patients who were non-T/T genotypes were comparable
      and were not influenced by age. The results reveal an inverse relation between
      the level of fasting plasma homocysteine and age at onset of CAD in T/T
      homozygotes as opposed to no association in patients who were non-T/T genotypes.
      Additionally, these results show that hyperhomocysteinemia and the T/T genotype
      have a stronger effect on the pathogenesis of CAD when they are combined, and
      that a marked increase (>15 micromol/L) in fasting plasma homocysteine in T/T
      homozygotes is a risk factor for early onset of CAD.

PMID- 11950429
TI  - Practice patterns and outcomes of percutaneous coronary interventions in the
      United States: 1995 to 1997.
AB  - Randomized trials have demonstrated the superiority of coronary stents in
      combination with a platelet-focused pharmacologic approach in percutaneous
      coronary intervention (PCI). However, nationally representative data examining
      the impact of these technologies on patient outcomes and costs remain scarce.
      This study sought to determine the real-world impact of changes in the use of
      stents and anticoagulant agents in PCI on outcomes and costs. A nationally
      representative sample of 37,088 patients who underwent PCI from October 1995 to
      October 1997 was identified from in-patient hospital claims data acquired from
      HCIASachs. Utilization of coronary stents, antiplatelet and anticoagulant agents,
      and outcome measurements of in-hospital death, coronary artery bypass grafting
      (CABG), repeat PCI, bleeding, and costs were analyzed in 6-month intervals. Acute
      events (death, urgent CABG, or PCI) decreased (p <0.001), whereas use of stents,
      abciximab, or both, increased (p <0.001). Dosages of heparin and bleeding
      complications declined significantly (p <0.001) over the 2-year period. Heparin
      dosages were higher in patients who experienced bleeding or death than in those
      who did not (p <0.001). The average hospital length of stay decreased
      significantly (p <0.001), largely driven by a reduction in time between the
      procedure and hospital discharge. By the end of the study period, bleeding was
      the most frequent (5.5%) complication of PCI and was associated with considerable
      costs, adding $10,225 to baseline costs.

PMID- 11950430
TI  - Thrombin generation and fibrinolytic activities among patients receiving reduced
      dose alteplase plus abciximab or undergoing direct angioplasty plus abciximab for
      acute myocardial infarction.
AB  - The purpose of this study was to determine the impact of these 2 reperfusion
      strategies (reduced-dose alteplase plus abciximab or direct angioplasty plus
      abciximab) on fibrinolytic and thrombin generation activities. The effect of
      reduced-dose alteplase plus abciximab and direct angioplasty plus abciximab on
      hemostatic factors is unknown. Of 70 patients with acute myocardial infarction of
      < or = 6 hours, 34 were randomized to reduced-dose alteplase (35 to 50 mg in 1
      hour) and 36 to direct angioplasty. A standard bolus and infusion dose of
      abciximab was administered to all patients. Blood specimens were collected at
      baseline, and at 1, 4, 12, and 24 hours. The following parameters were assayed:
      fibrinogen, plasminogen and antiplasmin activities, tissue plasminogen activator
      antigen, D-dimer, prothrombin fragments F1 + 2, and thrombin/antithrombin III
      complexes. Among patients treated with reduced-dose alteplase plus abciximab, the
      fibrinogen level decreased by 28.4% in the first hour (11.7 +/- 3.4 vs 7.8 +/-
      2.5 micromol/L, p <0.001). Correspondingly, plasminogen and antiplasmin
      activities decreased by 43.8% (p <0.001) and 59.1% (p <0.001), respectively.
      Prothrombin fragments F1 + 2 increased from 2.2 +/- 1.7 to 4.2 +/- 1.6 nmol/L (1
      hour) (p <0.001) and thrombin/antithrombin III increased from 16.3 +/- 15.0 to
      33.5 +/- 19.9 microg/L (1 hour) (p <0.001). Conversely, in the direct angioplasty
      group, there was a marginal elevation in fibrinogen level at 1 hour (10.2 +/- 2.4
      vs 10.6 +/- 2.0 micromol/L, p = 0.064) despite a significant reduction in
      plasminogen and an increase in tissue plasminogen activator levels. There was no
      significant change in prothrombin fragments F1 + 2 and thrombin/antithrombin III
      levels. Thus, there was considerable fibrinolytic activity with reduced-dose
      alteplase plus abciximab; thrombin generation was not prevented. Among patients
      treated with direct angioplasty, there was some endogenous fibrinolytic activity,
      but there was no significant thrombin generation.

PMID- 11950431
TI  - Evidence that angiotensin-converting enzyme inhibitor use diminishes the need for
      coronary revascularization after stenting.
AB  - Restenosis after stenting, in contrast to balloon angioplasty, is predominantly
      due to neointima formation. Angiotensin-converting enzyme (ACE) inhibitors
      diminish neointima formation in animal models of arterial injury. In an
      observational study, 1,598 patients who were treated from 1994 to 1997 with
      coronary stents and prospectively followed for clinical events were divided into
      2 groups: those receiving ACE inhibitors at the time of stenting (n = 345) and
      those who did not (n = 1,253). Multivariate logistic regression was used to
      adjust for imbalances between populations with regard to elements relevant to
      risk of 12-month coronary revascularization, which was the primary study end
      point. After adjustment, ACE inhibitor usage remained significantly protective
      against revascularization (odds ratio [OR] 0.46, 95% confidence interval 0.29 to
      0.73, p = 0.001). Protection was not observed in patients treated with balloon
      angioplasty alone during the same period (OR 1.06, p = 0.33), which is consistent
      with the results of prior randomized trials. ACE inhibitors appear to decrease
      late revascularization, possibly due to a reduction in restenosis after coronary
      stenting.

PMID- 11950432
TI  - Evaluation of a balloon occlusion and aspiration system for protection from
      distal embolization during stenting in saphenous vein grafts.
AB  - Distal embolization after angioplasty in degenerated saphenous vein grafts (SVGs)
      results in high rates of periprocedural myonecrosis and mortality. Temporary
      protection of the distal microcirculation with aspiration of dislodged debris may
      improve the safety of SVG intervention. To evaluate the feasibility, safety, and
      efficacy of distal protection using the PercuSurge GuardWire Occlusion and
      Aspiration System, 103 consecutive patients undergoing planned stenting of 105
      SVG lesions were prospectively enrolled in a multinational, multicenter study.
      Before angioplasty, protection of the distal circulation was achieved with the
      PercuSurge GuardWire distal balloon occlusion system, followed by stenting and
      debris aspiration. Quality assurance measures in the study included independent
      on-site data monitoring, clinical event adjudication, data analysis, and use of
      multiple core laboratories. Mean graft age was 8.9 +/- 4.0 years. The duration of
      distal balloon inflation was 5.4 +/- 3.7 minutes; premature balloon deflation for
      ischemia was not required in any patient. Macroscopically visible red and/or
      yellow debris was extracted in 91% of patients. By core lab analysis,
      postprocedural Thrombolysis In Myocardial Infarction-III flow was present in
      98.9% of grafts (vs 83.5% before intervention). No patient developed angiographic
      evidence of no reflow or distal embolization. Postprocedural creatine
      phosphokinase MB isozyme levels were elevated to >3 x normal in only 5 patients
      (5%), and 97 patients (94%) were free of major adverse events at 30 days. We
      conclude that the GuardWire distal balloon occlusion and aspiration system is an
      effective and safe method for protecting distal microcirculation from the adverse
      consequences of embolization during mechanical intervention of degenerated SVGs.

PMID- 11950433
TI  - Brachial artery distensibility and relation to cardiovascular risk factors in
      healthy young adults (The Bogalusa Heart Study).
AB  - Arterial distensibility decreases with age and atherosclerosis leading to
      increased pulse pressure (PP) and increased left ventricular work, resulting in
      left ventricular hypertrophy, a risk factor for cardiovascular morbidity.
      Brachial artery pulse curve data were collected using the DynaPulse 2000A.
      Distensibility measured in 920 healthy young adults (40% men, 70% white, age
      range 18 to 38 years) was compared with levels of cardiovascular risk factors.
      Laboratory, anthropometric, blood pressure (BP), and heart rate measurements were
      also obtained. Distensibility tended to decrease with age, reaching significance
      in women (p <0.05). Whites had greater distensibility adjusted for age than
      blacks, with women more than men (p <0.05). Distensibility adjusted for PP was
      negatively correlated with measures of body size, BP, glucose, insulin, low
      density lipoprotein cholesterol, very low density lipoprotein cholesterol, and
      age (p <0.05). When distensibility was plotted as a function of PP to control for
      distending pressure, the lowest quintiles of systolic, diastolic, and mean
      arterial BPs tended to have greater distensibility. No differences were seen by
      quintiles of lipids. In multivariate analyses, BP, age, anthropometric measures,
      gender, and very low density lipoprotein cholesterol entered the model (r(2) =
      0.56; p <0.02). Thus, brachial artery distensibility, which includes a
      normalization factor to control for body size, showed race and gender differences
      (whites and women had greater distensibility than blacks and men, respectively),
      even after adjustment for age. Stiffer vessels with decreased distensibility were
      seen in subjects with higher levels of cardiovascular risk factors across the
      range of normal PP. Therefore, noninvasive measures of distensibility are useful
      in measuring subclinical vascular changes related to arteriosclerosis.

PMID- 11950434
TI  - Effect of a multimodality natural medicine program on carotid atherosclerosis in
      older subjects: a pilot trial of Maharishi Vedic Medicine.
AB  - Although the onset and progression of coronary heart disease (CHD) involve
      multiple risk factors, few intervention studies have attempted to modify these
      factors simultaneously. This pilot study tested the effect of a multimodality
      intervention involving dietary, exercise, herbal food supplement, and stress
      reduction approaches from a traditional system of natural medicine, Maharishi
      Vedic Medicine (MVM). The primary outcome measure was carotid intima-media
      thickness (IMT), a noninvasive measure of peripheral atherosclerosis and
      surrogate measure of coronary atherosclerosis. Comparison groups included modern
      medicine (conventional dietary, exercise, and multivitamin approaches) and usual
      care (no added intervention). Of 57 healthy seniors (mean age 74 years)
      randomized to the 3 treatment groups, 46 completed IMT post-testing. Carotid IMT
      was determined by B-mode ultrasound before and after 1 year of treatment. IMT
      decreased in a larger fraction of MVM subjects (16 of 20) than in the modern (5
      of 9) and usual care (7 of 14) groups combined (i.e., 12 of 23; odds ratio 3.7, p
      = 0.05). For subjects with multiple CHD risk factors ("high-risk" subjects, n =
      15), IMT decreased more in the MVM (-0.32 +/- 0.23 mm, mean +/- SD) than in the
      usual care (+0.022 +/- 0.085; p = 0.009) or modern (-0.082 +/- 0.095, p = 0.10)
      groups. Within-group reductions in IMT were significant for all MVM subjects (
      0.15 +/- 0.21, n = 20, p = 0.004) and for high-risk MVM subjects (n = 6, p =
      0.01). These results show that this multimodality traditional approach can
      attenuate atherosclerosis in older subjects, particularly those with marked CHD
      risk.

PMID- 11950435
TI  - Outcome of staged surgical approach to neonates with single left ventricle and
      moderate size bulboventricular foramen.
AB  - Neonates with double-inlet left ventricle or tricuspid atresia with transposed
      great arteries and a bulboventricular foramen (BVF) area <2 cm(2)/m(2) develop
      BVF obstruction. This study examined the outcome of neonates with BVF area
      between 1 and 2 cm(2)/m(2) whose BVF was bypassed after the neonatal period. We
      reviewed 29 neonates with double-inlet left ventricles (n = 18) or tricuspid
      atresia (n = 11) and transposed great arteries. The study group consisted of 9
      patients with neonatal BVF areas of 1 to 2 cm(2)/m(2) who did not undergo repair
      of the BVF obstruction as a neonate. The comparison group consisted of 8 "ideal"
      patients without BVF obstruction. Precavopulmonary shunt data from cardiac
      catheterization and echocardiogram and outcomes of the cavopulmonary shunt were
      compared. Study group patients developed a mild BVF gradient (18 +/- 10 mm Hg by
      cardiac catheterization) by a mean of 7 months. Left ventricular wall thickness,
      however, remained in the normal range (4.2 +/- 0.3 mm) and was not statistically
      different from the comparison group (4.1 +/- 0.4 mm). No difference was found in
      the precavopulmonary mean pulmonary artery pressure (15 +/- 5 vs 15 +/- 6 mm Hg),
      transpulmonary gradient (8 +/- 4 vs 8 +/- 5 mm Hg), and left ventricular end
      diastolic pressure (7 +/- 2 vs 8 +/- 3 mm Hg). One patient in the study group
      died from respiratory syncytial virus pneumonia while awaiting cavopulmonary
      shunt. Neither group had mortality from the cavopulmonary shunt. The lengths of
      hospital stay were comparable (8.3 +/- 3.7 vs 8.9 +/- 6.0 days). Thus, neonates
      with BVF area between 1 and 2 cm(2)/m(2) develop mild but hemodynamically
      insignificant BVF gradient by 7 months of age. This group of patients can be
      managed safely with relief of BVF obstruction later in infancy.

PMID- 11950437
TI  - It's time to start treating obesity.

PMID- 11950436
TI  - Prediction of mortality in heart transplant recipients by stress technetium-99m
      tetrofosmin myocardial perfusion imaging.
AB  - Cardiac allograft vasculopathy is a major cause of mortality in heart transplant
      recipients. The aim of this study was to assess the prognostic value of stress
      myocardial perfusion imaging in heart transplant recipients. We studied 166
      patients (age 54 +/- 10 years, 140 men) by symptom-limited bicycle exercise or
      dobutamine (up to 40 microg/kg/min) stress myocardial perfusion imaging 7.4 +/-
      2.5 years after heart transplantation. An intravenous dose of 370 MBq of
      technetium-99m tetrofosmin was injected at peak stress and 24 hours after the
      stress test. An abnormal test was defined as reversible or fixed perfusion
      defects. Perfusion abnormalities were detected in 55 patients (33%). During a
      median follow-up of 2.5 years, 54 deaths (33%) occurred, 16 of which were due to
      cardiac causes. The incidence of perfusion abnormalities was higher in patients
      with subsequent cardiac death than in patients without subsequent cardiac death
      (69% vs 29%, p = 0.01). In an incremental multivariate Cox analysis, cardiac
      death was not predicted by age, gender, duration of transplantation, number of
      rejection episodes, or cytomegalovirus infection. In the next step, stress test
      parameters were added. The peak rate-pressure product was the only significant
      predictor at this step (risk ratio 0.84, 95% confidence interval 0.73 to 0.97,
      chi-square 7.7, p = 0.006). In the final step, the presence of abnormal
      myocardial perfusion was an independent predictor of cardiac death (risk ratio
      3.5, 95% confidence interval 1.6 to 11.7, chi-square 4.7, incremental to clinical
      and stress test variables, p = 0.01). It is concluded that stress myocardial
      perfusion imaging with technetium-99m tetrofosmin single-photon emission computed
      tomography provides incremental data for the prediction of cardiac death in heart
      transplant recipients.

PMID- 11950438
TI  - The coxib story: some lessons and more questions.

PMID- 11950439
TI  - Reduced levels of insulin-like growth factor-1 in patients with angina pectoris,
      positive exercise stress test, and angiographically normal epicardial coronary
      arteries.

PMID- 11950440
TI  - Gender differences in clinical outcome after coronary artery stenting with use of
      glycoprotein IIb/IIIa inhibitors.

PMID- 11950441
TI  - Patency of coronary artery bypass grafts in patients with heparin-induced
      thrombocytopenia.

PMID- 11950442
TI  - Association of systemic inflammatory state with troponin I elevation after
      elective uncomplicated percutaneous coronary intervention.

PMID- 11950443
TI  - A novel method for angiography of the left internal thoracic artery from a right
      arm approach using a YUMIKO-LITA catheter.

PMID- 11950444
TI  - Significance of sustained monomorphic ventricular tachycardia induced with short
      coupling intervals in patients with ischemic cardiomyopathy.

PMID- 11950445
TI  - Assessment of autonomic function in subjects with early repolarization.

PMID- 11950446
TI  - Comparison of impedance cardiography with invasive hemodynamic measurements in
      patients with heart failure secondary to ischemic or nonischemic cardiomyopathy.

PMID- 11950447
TI  - Comparison of effects of carvedilol versus metoprolol on cytokine levels in
      patients with idiopathic dilated cardiomyopathy.

PMID- 11950448
TI  - Changing trends in incidence and predictors of radiographic contrast nephropathy
      after percutaneous coronary intervention with use of fenoldopam.

PMID- 11950449
TI  - Aortic distensibility is increasing in elite athletes.

PMID- 11950450
TI  - The difference between a mentor and a teacher.

PMID- 11950451
TI  - Angiographic findings in monozygotic twins with coronary artery disease.

PMID- 11950452
TI  - Overstretch stent injury to the rat aorta leads to in-stent restenosis.

PMID- 11950453
TI  - Notes from a recent visitor to Berlin: on myocarditis, effect of coronary
      angiography on thyroid function, and Virchow's inflammatory theory of
      atherosclerosis.

PMID- 11950454
TI  - Trauma in children and adolescents: risk and treatment of psychiatric sequelae.
AB  - The recent wave of terrorism affecting the United States and other countries
      raises concerns about the welfare of children and adolescents. This review is
      designed to address such concerns by summarizing data from two scientific areas.
      First, a series of recent studies examine psychiatric outcomes over time in
      children exposed to various forms of trauma. This review summarizes data on the
      various psychiatric consequences of childhood exposure to trauma, with specific
      emphasis on identifying factors that predict psychiatric outcome. Prior studies
      suggest that level of exposure, evidence of psychopathology before trauma
      exposure, and disruption in social support networks consistently emerge as strong
      predictors of psychopathology following exposure to trauma. Hence, clinicians
      might monitor children exposed to trauma most closely when they present with
      these risk factors. Second, a series of randomized controlled trials documents
      the beneficial effects of cognitive behavioral therapy (CBT) in children exposed
      to sexual abuse. When combined with other data from open studies and controlled
      trials in nontraumatized children, these studies suggest that CBT represents a
      logical therapeutic option for children developing anxiety symptoms following the
      recent wave of terrorism. In terms of psychopharmacological treatments, data from
      randomized controlled trials in traumatized children have not been generated, but
      recent studies in other groups of children exhibiting symptoms of anxiety or
      depression suggest the utility of selective serotonin reuptake inhibitors.

PMID- 11950455
TI  - Acute stress reactions in adults.
AB  - This article summarizes the literature on acute reactions to traumatic stress in
      adults. It describes their morphology, natural course, long-term outcome, and
      underlying biological factors, and outlines directions for management and
      research. It assumes two categories of responses: those that mediate survival and
      those related to learning and adaptation. The complementary roles of fear
      conditioning, processing novelty, and adjusting to change are discussed.

PMID- 11950456
TI  - Superior temporal gyrus volumes in maltreated children and adolescents with PTSD.
AB  - BACKGROUND: The structure and function of the superior temporal gyrus (STG), a
      structure involved in receptive and nonverbal auditory and language processing,
      is understudied in posttraumatic stress disorder (PTSD). Event-related potential
      abnormalities were previously reported in PTSD, implicating the existence of
      dysfunction in the primary auditory cortex and adjacent anterior auditory cortex
      of the STG in adult PTSD. METHODS: Anatomic magnetic resonance imaging (MRI)
      volumetric analysis of the superior temporal gyrus were performed in 43
      maltreated children and adolescents with PTSD and 61 nonmaltreated healthy
      control subjects. RESULTS: Unadjusted STG gray matter volumes were larger in
      maltreated subjects with PTSD than in control subjects, whereas STG white matter
      volumes were smaller in maltreated subjects with PTSD than in control subjects.
      After adjusting for differences in cerebral volume, right, left, and total
      superior temporal gyrus volumes were relatively larger in PTSD subjects compared
      with control subjects. After covarying for differences in cerebral gray matter
      volumes, regression analysis showed that PTSD subjects had significantly greater
      STG gray matter volumes in most, and in particularly right-sided STG
      measurements. Furthermore, findings of significant side-by-diagnosis interactions
      for STG and STG gray but not white matter STG volumes suggest that there is a
      more pronounced right > left asymmetry in total and posterior STG volumes but a
      loss of the left > right asymmetry seen in total, anterior, and posterior STG
      gray matter volumes in PTSD subjects compared with control subjects. CONCLUSIONS:
      These STG findings may suggest developmental alterations in maltreatment-related
      pediatric PTSD.

PMID- 11950457
TI  - Superior temporal gyrus volumes in pediatric generalized anxiety disorder.
AB  - BACKGROUND: The essential symptoms of generalized anxiety disorder (GAD) are
      intrusive worry about everyday life circumstances and social competence, and
      associated autonomic hyperarousal. The amygdala, a brain region involved in fear
      and fear-related behaviors in animals, and its projections to the superior
      temporal gyrus (STG), thalamus, and to the prefrontal cortex are thought to
      comprise the neural basis of our abilities to interpret social behaviors. Larger
      amygdala volumes were previously reported in pediatric GAD; however, the brain
      regions involved in social intelligence were not examined in this pilot study.
      METHODS: Magnetic resonance imaging (MRI) was used to measure the STG, thalamus,
      and prefrontal volumes in 13 medically healthy child and adolescent subjects with
      generalized anxiety disorder (GAD) and 98 comparison subjects, who were at low
      familial risk for mood and psychotic disorders. Groups were similar in age,
      gender, height, weight, handedness, socioeconomic status, and full-scale IQ.
      RESULTS: The total, white matter, and gray matter STG volumes were significantly
      larger in GAD subjects compared with control subjects. Thalamus and prefrontal
      lobe volumes did not differ between groups. Findings of significant side-by
      diagnosis interactions for STG and STG white matter volumes suggest that there is
      a more pronounced right > left asymmetry in total and STG white matter volumes in
      pediatric GAD subjects compared with control subjects. A significant correlation
      between the STG white matter percent asymmetry index with the child report of the
      Screen for Child Anxiety Related Emotional Disorders Scale was seen. CONCLUSIONS:
      These data agree with previous work implicating posterior right-hemispheric
      regions in anxiety disorders and may suggest developmental alterations in
      pediatric GAD.

PMID- 11950458
TI  - Temperamental correlates of disruptive behavior disorders in young children:
      preliminary findings.
AB  - BACKGROUND: Our objective was to test the hypothesis that temperamental
      behavioral disinhibition measured in early childhood would be associated with
      disruptive behavior disorders. METHODS: We used variables from laboratory-based
      behavioral observations originally devised to assess behavioral inhibition to
      construct a theory-based a priori definition of "behavioral disinhibition" in 200
      young children at-risk for panic disorder, depression, or both and 84 children of
      parents without anxiety or major depressive disorder. We then compared
      behaviorally disinhibited and nonbehaviorally disinhibited children on rates of
      DSM-III-R disorders and measures of academic and social dysfunction. RESULTS:
      Behavioral disinhibition was significantly associated with higher rates of
      disruptive behavior disorders and mood disorders. Children with behavioral
      disinhibition were significantly more likely than nondisinhibited, noninhibited
      children to have attention-deficit/hyperactivity disorder (ADHD) and to have
      comorbid mood and disruptive behavior disorders. Moreover, disinhibited children
      had lower Global Assessment of Functioning Scale scores and were more likely to
      have been in special classes and to have problems with school behavior and
      leisure activities. CONCLUSIONS: These results suggest that behavioral
      disinhibition may represent a temperamental precursor to disruptive behavior
      problems, particularly ADHD. Longitudinal studies using behavioral assessments of
      behavioral disinhibition are needed to confirm these findings.

PMID- 11950459
TI  - Diurnal salivary cortisol in pediatric posttraumatic stress disorder.
AB  - BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in
      the pathophysiology of posttraumatic stress disorder (PTSD). Additional
      information on basal cortisol levels in children exposed to trauma and
      experiencing PTSD symptoms may contribute to the understanding of the role of
      this axis in PTSD. METHODS: Fifty-one children (30 boys and 21 girls, mean age
      10.7 years) with a history of exposure to trauma and PTSD symptoms were compared
      with 31 age- and gender-matched healthy control subjects. Salivary cortisol was
      obtained from participants during home measurements and was collected four times
      a day (prebreakfast, prelunch, predinner, and prebed) for up to 3 consecutive
      days. RESULTS: The clinical group demonstrated significantly elevated cortisol
      levels when compared with the control group. In addition, exploratory analyses
      revealed that girls with PTSD symptoms had significantly elevated cortisol levels
      when compared with boys with PTSD symptoms. CONCLUSIONS: The physiologic response
      of children with history of trauma and with PTSD symptoms may be characterized by
      heightened adrenal activity.

PMID- 11950460
TI  - Reduced startle reactivity and plasticity in transgenic mice overexpressing
      corticotropin-releasing hormone.
AB  - BACKGROUND: Corticotropin-releasing hormone (CRH) hyperactivity in transgenic
      mice overexpressing CRH in the brain (CRH-OE(2122)) appears to be associated with
      chronic stress-like alterations, including increased CRH content in the
      hypothalamus, changes in hypothalamus-pituitary-adrenal axis regulation, and
      increased heart rate and body temperature. In the present study, we investigated
      if sensory information processing of startling auditory stimuli was affected in
      CRH-OE(2122) mice. METHODS: CRH-OE(2122) mice (on C57BL/6J background) were
      subjected to a number of procedures probing sensory information processing
      mechanisms, including the acoustic startle response, habituation, and prepulse
      inhibition of startle. RESULTS: CRH-OE(2122) mice displayed reduced acoustic
      startle reactivity and increased motor activity during startle testing compared
      to wild-type mice. Furthermore, transgenic mice did not show habituation of the
      startle response after repeated exposure to the auditory stimulus, or habituation
      across procedures. CRH-OE(2122) mice exhibited robust impairments of prepulse
      inhibition in two different paradigms. CONCLUSIONS: The results in CRH-OE(2122)
      mice indicate that chronic CRH hyperactivity is associated with reductions in
      startle reactivity, habituation, and prepulse inhibition. The latter two
      abnormalities are also observed in schizophrenia patients. We conclude that
      chronic CRH excess may reduce behavioral reactivity to environmental stimuli and
      impair information processing mechanisms.

PMID- 11950461
TI  - Evidence for a susceptibility locus for panic disorder near the catechol-O
      methyltransferase gene on chromosome 22.
AB  - BACKGROUND: A well-characterized single nucleotide polymorphism (472G/A-Val/Met
      SNP8) in the coding sequence of the catechol-O-methyltransferase (COMT) gene
      leads to a three- to fourfold difference in enzymatic activity and clinical and
      animal studies suggest a role in anxiety states like panic disorder. METHODS:
      Subjects from 70 panic disorder pedigrees, and 83 "triads", were genotyped at
      seven single nucleotide polymorphisms (SNPs), polymorphic microsatellites in the
      first intron of COMT and approximately 339kb upstream of COMT (D22S944) and
      analyzed for genetic association and linkage. RESULTS: Linkage analysis showed
      elevated LOD scores for 472G/A (SNP 8), silent exon 3 substitution (186C/T-SNP
      5), and the marker D22S944 (2.88, 2.62, and 2.93, respectively), using a variety
      of diagnostic and genetic models. Association tests were not significant for the
      SNPs, but were highly significant for D22S944 (p =.0001-.0003). One three-marker
      haplotype formed from the above three polymorphisms was significantly associated
      with panic disorder (p =.0001), as was the "global" p value for this combination
      (p =.005). In addition, numerous haplotypes with combinations of D22S944 and COMT
      SNPs were found to be significantly associated with panic disorder. CONCLUSIONS:
      Our findings provide strong evidence for a susceptibility locus for panic
      disorder either within the COMT gene or in a nearby region of chromosome 22.

PMID- 11950463
TI  - Some amino sugars structurally related to 6-deoxymannojirimycin precursors
      prepared from methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosid-5
      ulose and methyl 2,3-O-isopropylidene-alpha-D-lyxo-pentodialdo-1,4-furanoside.
AB  - Methyl (5S)-5-C-amino-5-cyano-5-deoxy-2,3-O-isopropylidene-alpha-D-lyxofuranoside
      has been synthesised from methyl 2,3-O-isopropylidene-alpha-D-lyxo-pentodialdo
      1,4-furanoside, applying the Strecker synthesis. Analogously, methyl (5S) and
      (5R)-5-C-amino-5-cyano-5,6-dideoxy-2,3-O-isopropylidene-alpha-D-lyxo
      hexofuranosides were prepared from methyl 6-deoxy-2,3-O-isopropylidene-alpha-D
      lyxo-hexofuranosid-5-ulose. The 5-S configuration was unambiguously determined by
      single-crystal X-ray diffraction analysis of corresponding N-acetyl derivatives.
      Conformations of five-membered rings are discussed. The conversion of N
      acetylated amino nitriles to N-acetylamino acid ethyl ester and amide,
      respectively, is also described.

PMID- 11950462
TI  - Occurrence of delusions during repetitive transcranial magnetic stimulation
      (rTMS) in major depression.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been
      suggested as a potentially useful treatment for major depression. Nonpsychotic
      depressed patients appear to have a better outcome than those with psychotic
      symptoms. METHODS: We report findings in a patient suffering from recurrent,
      nonpsychotic major depression (DSM-IV) who had 13 daily sessions of rTMS
      monotherapy within a 3 week period. RESULTS: During rTMS treatment, the patient
      developed recurrent severe delusions, which he had never experienced before.
      Psychotic symptoms remitted quickly with neuroleptic medication. CONCLUSIONS: In
      light of preclinical findings showing increased dopaminergic activity after rTMS
      treatment, occurrence of psychotic symptoms should be considered a potential side
      effect of rTMS treatment.

PMID- 11950464
TI  - An access to various sulfation patterns in dermatan sulfate: chemical syntheses
      of sulfoforms of trisaccharide methyl glycosides.
AB  - The syntheses are reported for the first time of alpha-L-IdopA2SO(3)-(1-->3)-beta
      D-GalpNAc4SO(3)-(1-->4)-alpha-L-IdopA2SO(3)-(1-->OMe), its disulfated analogue
      alpha-L-IdopA2SO(3)-(1-->3)-beta-D-GalpNAc-(1-->4)-alpha-L-IdopA2SO(3)-(1-->OMe),
      and of beta-D-GalpNAc4SO(3)-(1-->4)-alpha-L-IdopA2SO(3)-(1-->3)-beta-D
      GalpNAc4SO(3)-(1-->OMe), which represent structural fragments of dermatan
      sulfate, unavailable directly by chemical or enzymatic degradation of the
      glycosaminoglycan polymer. These molecules were readily obtained from a pair of
      key disaccharide intermediates, in which the relative difference of stability of
      the D-GalNAc 4-hydroxy protecting groups (acetate or pivalate) toward
      saponification conditions allowed access to various sulfoforms from a common
      precursor. For the preparation of these blocks, the 4-O-pivaloyl-D-galacto moiety
      was readily obtained through a one-pot stereospecific intramolecular nucleophilic
      displacement on an easily available 3-O-pivaloyl-D-gluco precursor, and the L
      IdoA moiety through selective radical oxidation at C-6 of a L-ido 4,6-diol
      derivative with oxoammonium salts.

PMID- 11950465
TI  - Synthesis of oxidized methyl 4-O-methyl-beta-D-glucopyranoside and methyl beta-D
      glucopyranosyl-(1-->4)-beta-D-glucopyranoside derivatives as substrates for
      fluorescence labeling reactions.
AB  - The synthetic cellulose model compounds methyl 4-O-methyl-beta-D-glucopyranoside
      and methyl 4-O-methyl-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranoside and
      related 6-O-protected intermediates were oxidized in good to fair yields using
      Swern-conditions or bromine/bis(tributyltin) oxide, respectively, to afford
      compounds containing 6-aldehyde, 3-keto, and 2,3-diketo groups. Cellobiose and
      oxidized monosaccharides were then labeled with the carbonyl-selective
      fluorescence marker 9-(7-amino-1,4,7-trioxaheptyl)-9H-carbazolecarboxamide
      (CCOA). The labeled derivatives serve as model compounds for the determination of
      minute amounts of carbonyl groups in cellulosic polysaccharides.

PMID- 11950466
TI  - Regulation of fructosyltransferase activity by carbohydrates, in solution and
      immobilized on hydroxyapatite surfaces.
AB  - We tested the effect of several carbohydrates on the activity of cell-free
      fructosyltransferases (FTF) in solution and immobilized onto hydroxyapatite (HA)
      and found an inhibitory dose-dependent effect of glucose on FTF activity, both on
      the surface and in solution. Glucose at 160 mM inhibits FTF activity by 75% both
      on HA and in solution. Fructose at 160 mM inhibited FTF activity by 25% in
      solution and by 15% on HA. Levan inhibited FTF activity by 30% in solution, while
      dextrans and inulin had a limited effect on FTF activity. Circular dichroism and
      infrared analysis demonstrated no major changes in the chemical structure of
      fructans synthesized by cell-free FTF on HA and in solution, in the presence or
      absence of glucose. However, as verified by size-exclusion chromatography,
      glucose inhibited the synthesis of high molecular-weight fructans. The results
      indicate that glucose, a byproduct of the FTF enzymatic reaction, is the main
      carbohydrate affecting FTF activity. Selective inhibition of high molecular
      weight fructan production by glucose, may indicate that two mechanisms are
      involved in the synthesis of fructans, both in solution and on the surface.

PMID- 11950467
TI  - Characterization of water-soluble hemicelluloses from spruce and aspen employing
      SEC/MALDI mass spectroscopy.
AB  - Partly depolymerized hemicelluloses isolated from wood chips of spruce and aspen
      employing microwave treatment were resolved using size-exclusion chromatography
      (SEC) into oligo- and polysaccharide fractions containing components with a
      narrow range of sizes, as determined by MALDI mass spectroscopy. The degree of
      substitution with acetyl moieties (DS) was also calculated on the basis of the
      MALDI-MS spectra obtained prior to and following deacetylation. For spruce
      hemicelluloses, the low molecular mass fraction contained small arabino-4-O
      methylglucuronoxylan oligosaccharides, with DP values ranging from 4 to
      approximately 20, separated primarily on the basis of their charge density. The
      fraction eluted last consisted of an O-acetyl-(galacto)glucomannan polysaccharide
      of peak-average DP value (DP(p)) 14. The degree of substitution with acetyl
      groups (DS) decreased with decreasing DP, a value DS of 0.39 being obtained for
      the fraction with DP(p) 12. For the aspen hemicelluloses, the SEC fractions
      eluted first contained an acidic O-acetyl-4-O-methylglucuronoxylan polysaccharide
      with DP ranging from 10 to approximately 28 and an average DS of approximately
      0.75. The fractions eluted last consisted of oligosaccharide mixtures composed
      primarily of small neutral O-acetyl-xylooligosaccharides (DP(p) 6, DS 0.41),
      together with minor quantities of an O-acetyl-glucomannan.

PMID- 11950468
TI  - Structure of a fucoidan from the brown seaweed Fucus evanescens C.Ag.
AB  - A fucoidan consisting of L-fucose, sulfate and acetate in a molar proportion of
      1:1.23:0.36 was isolated from the Pacific brown seaweed Fucus evanescens. The
      structures of its desulfated and de-O-acetylated derivatives were investigated by
      1D and 2D (1)H and (13)C NMR spectroscopy, and the data obtained were confirmed
      by methylation analysis of the native and desulfated polysaccharides. The
      fucoidan was shown to contain a linear backbone of alternating 3- and 4-linked
      alpha-L-fucopyranose 2-sulfate residues: -->3)-alpha-L-Fucp(2SO(3)(-))-(1-->4)
      alpha-L-Fucp(2SO(3)(-))-(1-->. Additional sulfate occupies position 4 in a part
      of 3-linked fucose residues, whereas a part of the remaining hydroxyl groups is
      randomly acetylated.

PMID- 11950469
TI  - Extracellular polysaccharides of a bacterium associated with a fungal canker
      disease of Eucalyptus sp.
AB  - Extracellular polysaccharides (EPSs) produced by an Erwinia sp associated with a
      fungal canker disease of Eucalyptus were fractionated into one polysaccharide
      that was identified with that produced by Erwinia chrysanthemi strains SR260,
      Ech1, and Ech9, and the other distinctively different from any other EPS produced
      by E. chrysanthemi strains so far studied. Their structures were determined using
      a combination of chemical and physical techniques including methylation analysis,
      low pressure gel-filtration, and anion-exchange chromatographies, high-pH anion
      exchange chromatography, mass spectrometry and 1D and 2D 1H NMR spectroscopy. The
      new polysaccharide, identified as EPS Teranera, has the following structure:
      [structure: see text] The molecular weights of the polysaccharides range from 3.2
      6.2 x 10(5) and their hydrodynamic properties are those of polydisperse,
      polyanionic biopolymers with pseudoplastic, non-thixotropic flow characteristics
      in aqueous solutions.

PMID- 11950471
TI  - 5-Azido neuraminic acid thioglycoside as sialylation donor.
AB  - 5-Azido neuraminic acid thioglycoside with O-benzyl protecting groups was
      synthesized. The sialylations of this new donor type showed good alpha
      selectivities for certain primary hydroxyls.

PMID- 11950470
TI  - Structural and physicochemical characterization of the inclusion complexes of
      cyclomaltooligosaccharides (cyclodextrins) with melatonin.
AB  - The stoichiometry, geometry, stability, and solubility of the inclusion complexes
      of melatonin (MLT) with native cyclomaltooligosaccharides (alpha-, beta- or gamma
      cyclodextrins, CDs) are determined experimentally by high-resolution NMR
      spectroscopy, calorimetric and solubility measurements, and mass spectrometry.
      The observed differences are discussed in terms of molecular recognition
      expression of the host-guest (h-g) interactions within the hydrophobic CDs
      cavities of different size. The 1:1 h-g stoichiometry in water solution prevails
      at low CD concentrations; the trend to form higher order associations is observed
      at increasing CD concentrations. The stability order beta-CD>gamma-CD>alpha-CD
      for the complexes in water solution and beta-CD>alpha-CD>gamma-CD for the
      protonated or alkali-cationated complexes in the gas phase are rationalized on
      the grounds of the structural data from NMR spectroscopy and of the thermodynamic
      parameters from calorimetric measurements.

PMID- 11950472
TI  - Production of N-acetyl-D-glucosamine from alpha-chitin by crude enzymes from
      Aeromonas hydrophila H-2330.
AB  - The selective and efficient production of N-acetyl-D-glucosamine (GlcNAc) was
      achieved from flake type of alpha-chitin by using crude enzymes derived from
      Aeromonas hydrophila H-2330.

PMID- 11950473
TI  - Can the stereochemical outcome of glycosylation reactions be controlled by the
      conformational preferences of the glycosyl donor?
AB  - Previous static and dynamical density functional theory studies of the 2,6-di-O
      acetyl-3,4-O-isopropylidene-D-galactopyranosyl cations and their methanol adducts
      has led to an hypothesis that these cations exist in two families of conformers
      characterized as (2)S(O) and B(2,5), respectively. These families differ by ring
      inversion, each with its own reactivity. New calculations on the 2,6-di-O-acetyl
      3,4-di-O-methyl-D-galactopyranosyl cation confirmed these trends. Removing the
      isopropylidene group allows more flexibility, but two families of conformers can
      be discerned with the monocyclic oxocarbenium ions in the E(3) conformation and
      the bicyclic dioxolenium ions in the (4)H(5) conformation. Attack on the beta
      face of these monocyclic cations is favored by hydrogen bonding and the anomeric
      effect. The experimentally observed high beta-stereoselectivity of mannopyranosyl
      donors and high alpha-stereoselectivity of glucopyranosyl donors with the 4,6-O
      benzylidene protecting groups can be rationalized assuming that the trans-fused
      1,3-dioxane ring allows population of only one family of conformers. The
      combination of hydrogen bonding and conformational changes of the pyranose ring
      in response to the C-5[bond]O-5[bond]C-1[bond]C-2 torsion angle changes are
      identified as key factors in stereoselectivity. Based on these observations a
      strategy to design face discriminated glycosyl donors that exist predominantly in
      only one family of conformers is proposed.

PMID- 11950475
TI  - The retained placenta-new insights into an old problem.

PMID- 11950476
TI  - Risk factors in miscarriage: a review.
AB  - Miscarriage is one of the most frequent problems in human pregnancy. The most
      widely accepted definition is that proposed by the World Health Organization
      (WHO) in 1977. The incidence among clinical pregnancies is about 12-15% but
      including early pregnancy losses it is 17-22%. The only two etiologic factors
      recognized by all authors are uterine malformations and parental balanced
      chromosomal rearrangements. There have been many other suggested risk factors. In
      this revision we discuss these.

PMID- 11950477
TI  - Surgical techniques used during caesarean section operations: results of a
      national survey of practice in the UK.
AB  - OBJECTIVE: To determine what surgical techniques are used by obstetricians in the
      UK for elective and emergency caesarean section operations. STUDY DESIGN: A
      postal questionnaire to all members and fellows of the Royal College of
      Obstetricians and Gynaecologists (RCOG) resident in the UK, requesting
      information about the use of surgical techniques and antibiotic and anticoagulant
      prophylaxis for elective and emergency caesarean sections. RESULTS: The response
      rate was 78.7%. A range of techniques was used for all procedures in caesarean
      section operations. Only a few techniques were used by more than 80% of
      obstetricians, including double layer closure of the uterus, use of prophylactic
      antibiotics and Pfannenstiel abdominal entry (for elective caesarean sections).
      There were few large differences in practice between elective and emergency
      caesarean sections. In emergency operations, more obstetricians use the Joel
      Cohen method of abdominal entry (32.7 versus 16%) and more usually use
      prophylactic antibiotics and heparin (93.2 versus 85.4% and 45.8 versus 32.9%,
      respectively). CONCLUSIONS: There was wide variation in the surgical techniques
      used by obstetricians for caesarean section operations. There is an urgent need
      for future research to evaluate many aspects of caesarean section operations on
      substantive short- and long-term outcomes.

PMID- 11950478
TI  - Twenty-four hour pH monitoring during pregnancy and at postpartum: a preliminary
      study.
AB  - OBJECTIVE: To quantify the amount of acid refluxed in symptomatic pregnant women
      and compare this to the postpartum period. METHODS: Eight non complicated
      symptomatic pregnant women were enrolled. The mean age was 28+/-6.3 years and
      gestational age 26+/-4.4 weeks at inclusion. Repeated measurements were done at
      9.8+/-6.5 weeks postpartum. Esophageal manometry and 24h pH monitoring were
      performed at each time period. RESULTS: Heartburn (HB), regurgitation and
      dysphagia were the main presenting symptoms, however only regurgitation was
      significantly more frequent during pregnancy (P=0.01). Lower esophageal sphincter
      (LES) pressure was significantly lower during pregnancy (P=0.001). Twenty-four
      hour pH monitoring variables were worse and the number of reflux episodes and the
      upright reflux reached statistical significance (P=0.03, and 0.01, respectively).
      CONCLUSION: Pregnancy is associated with decreased LES pressure, more frequent
      episodes of reflux and upright reflux.

PMID- 11950479
TI  - Influence of maternal preeclampsia on recombinant human granulocyte colony
      stimulating factor effect in neutropenic neonates with suspected sepsis.
AB  - AIM: To evaluate the effect of recombinant human granulocyte colony-stimulating
      factor (rhG-CSF) in preterm neonates with suspected sepsis and severe neutropenia
      (<1500 mm(3)), and to define the influence of maternal preeclampsia on rhG-CSF
      activity. METHODS: Twenty neonates of normotensive mothers (NNMs) (GA 29.2+/-0.5
      weeks and BW 1.024+/-81 g) and 20 born to preeclamptic mothers (NPMs) (GA 29+/
      0.4 weeks and BW 946+/-55 g) were treated with rhG-CSF, 10 microg/kg per day for
      3 days. Complete blood counts were obtained at day 0 (before rhG-CSF
      administration) and 1-4, 6, 9, 20 and 30 days later. RESULTS: Absolute neutrophil
      count (ANC) increased rapidly (three-fold within 24h), and significantly (maximum
      approximately 20-25 times starting values) and remained within normal range in
      both groups. However, in NNMs a two-phase increase occurred with an early peak on
      day 2 and a further peak on day 6 giving significantly higher ANC (P<0.001) than
      for NPMs at days 2-4 and 6. NPMs showed a gradual ANC increase with a single late
      peak occurring 3 days later than NNMs (day 9). The highest peak values for ANC
      were similar (15,900+/-1395 mm(-3) for NNMs and 13,880+/-1097 mm(-3) for NPMs).
      Neutropenia was completely resolved within 2 days in NNMs and within 4 days in
      NPMs. CONCLUSION: Preeclampsia seemed to influence the course of the ANC in spite
      of rhG-CSF administration, and a higher daily-dose for NPMs with neutropenic
      sepsis may more rapidly resolve neutropenia by overcoming the preeclampsia
      associated inhibitor of rhG-CSF through a dose-dependent mechanism.

PMID- 11950480
TI  - Breech presentation at term: morbidity and mortality according to the type of
      delivery at Port Royal Maternity hospital from 1993 through 1999.
AB  - OBJECTIVE: To compare neonatal morbidity and mortality at Port Royal Maternity
      between 1993 and 1999 for infants with a singleton breech presentation born after
      37 weeks, according to planned mode of delivery. STUDY DESIGN: Retrospective
      study of 501 patients of whom vaginal delivery was planned in 322 (64%) or/and
      cesarean in 179 (36%). RESULTS: Severe neonatal morbidity was similar in the two
      groups (13/322, 4.0% versus 8/179, 4.5%; P=0.82); severe trauma morbidity was not
      significantly higher in the "planned vaginal delivery" group (3/322, 0.9% versus
      1/179, 0.06%; P=0.16); there were no long-term sequelae. Mortality was not higher
      when vaginal delivery was planned. CONCLUSION: We have not found in this series
      any excess of morbidity or mortality attributable to vaginal delivery of breech
      presentations. This work does not indicate that we should change our obstetrical
      practice in the light of other recently-published studies.

PMID- 11950481
TI  - Messenger ribonucleic acid levels of interleukin-1 beta, interleukin-6 and
      interleukin-8 in the lower uterine segment increased significantly at final
      cervical dilatation during term parturition, while those of tumor necrosis factor
      alpha remained unchanged.
AB  - OBJECTIVE: To investigate the content of tumor necrosis factor alpha, interleukin
      1 beta, interleukin-6 and interleukin-8 messenger ribonucleic acid (mRNA) in the
      lower uterine segment during term parturition. STUDY DESIGN: mRNA extracts from
      the lower uterine segment obtained from 53 women undergoing non-elective
      caesarean section at term were analyzed by semi-quantitative reverse
      transcriptase polymerase chain reaction. The patients were grouped according to
      cervical dilatation (less than 2 cm, n=18; 2 to less than 4 cm, n=13; 4-6 cm,
      n=7; more than 6 cm, n=15) at the time of caesarean section. RESULTS: Interleukin
      1 beta and interleukin-8 mRNA-contents at more than 6 cm cervical dilation were
      significantly higher than at less than 2 cm. The levels of interleukin-6 were
      already significantly increased in the 4-6 cm group, while the tumor necrosis
      factor alpha ribonucleic acid content did not change during parturition.
      CONCLUSION: The process of cervical dilatation during parturition at term is
      associated with an increased expression of interleukin-1 beta, interleukin-6 and
      interleukin-8 mRNA in the lower uterine segment. These findings support the
      theory that the activation of the inflammatory network plays an important role in
      the progress of cervical dilatation.

PMID- 11950482
TI  - Human chorionic gonadotropin attenuates the vascular response to angiotensin II.
AB  - OBJECTIVE: Our purpose was to investigate interactions between human chorionic
      gonadotropin (hCG) and angiotensin II (ANG II) in resistance arteries. STUDY
      DESIGN: Isolated pre-arteriolar vessels of female Sprague-Dawley rats were
      prepared from the mesenteric arcade and the mesometrium. Dose-response curves
      were recorded by means of an video-electronic arteriograph system. RESULTS: (1)
      hCG dilated mesenteric (MA; EC(50): 21+/-6.9 mU/ml) and uterine (UA; EC(50):
      256+/-44.3 mU/ml)) resistance arteries pre-constricted with ANG II. In the
      presence of glybenclamide (1 micromol/l), the response of MA was reduced by >50%.
      (2) After application of hCG for 1h, vasoconstriction by ANG II was significantly
      attenuated in MA. This effect was dose-dependent and was not observed in UA.
      Efficacy of ANG II could be restored, when hCG was followed by glybenclamide.
      CONCLUSIONS: hCG may contribute to the reduction in arterial tone seen early in
      human pregnancy. Its vascular effects are in part mediated by the activation of
      adenosine 5'-triphosphate-sensitive potassium channels, suggesting a protein
      kinase A dependent signaling pathway.

PMID- 11950483
TI  - Iron deficiency is prevalent in a sample of pregnant women at delivery in
      Germany.
AB  - OBJECTIVE: To determine the prevalence and risk factors of iron deficiency in
      pregnancy, since iron supplements are not routine in Germany. STUDY DESIGN:
      Soluble transferrin receptor (sTfR), ferritin, hemoglobin (Hb), C-reactive
      protein (CRP) and leucocyte counts were determined in venous blood samples of 378
      women before delivery; 191 of them filled in a questionnaire. Statistical
      analysis was performed using SPSS 9.0.1. RESULTS: CRP and leucocyte count
      correlated significantly with ferritin values, while sTfR values were
      independent. Iron deficiency (sTfR >3.3 mg/dl) was found in 40.7% of pregnant
      women, and anemia (Hb<11.0 g/dl) in 13.6%. Non-German nationality, low
      educational level and young maternal age were significant risk factors for iron
      deficiency, while alcohol use in pregnancy, iron and folic acid supplements were
      protective. After adjusting for all other factors in a logistic regression
      equation, not taking any iron supplements in pregnancy (odd ratios (OR) 3.3 and
      95% confidence interval (CI) 1.1-9.4), and young maternal age (OR 2.86 and 95% CI
      1.1-7.7) remained significant risks. CONCLUSION: Iron deficiency in pregnant
      women in Germany is prevalent; it could be prevented by routine iron supplements.

PMID- 11950484
TI  - The optimal dosage of ketanserin for patients with severe hypertension in
      pregnancy.
AB  - OBJECTIVE: To establish the optimal dosage of ketanserin in the treatment of
      severe hypertension in pregnancy. STUDY DESIGN: A double blind prospective
      randomised controlled trail, comparing 10 mg ketanserin given as intravenous
      boluses either every 10 or 20 min, until the therapeutic goal of 90 mmHg
      (diastolic blood pressure) was reached, to a maximum of eight boluses. Main
      outcome measures were treatment failures and caesarean sections for fetal
      distress. RESULTS: There was no difference in reaching the therapeutic goal
      between patients receiving 10 mg ketanserin either every 10 or 20 min.
      CONCLUSION: Ketanserin appears to be an attractive medicine in the treatment of
      severe hypertension in pregnancy, but the optimal dosage could not be
      established.

PMID- 11950485
TI  - A case controlled study of serial transabdominal amnioinfusions in the management
      of second trimester oligohydramnios due to premature rupture of membranes.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of transabdominal
      amnioinfusion in relieving oligohydramnios and improving pregnancy outcome. STUDY
      DESIGN: Pregnant women with oligohydramnios amniotic fluid index (AFI<5) and
      premature rupture of membranes (PROM) from <27 weeks gestation were managed with
      serial transabdominal amnioinfusions. Under ultrasonic guidance, a 20-gauge
      needle was instilled in the uterine cavity and normal saline was infused until
      the AFI was normal. Repeat amnioinfusion was done weekly if oligohydramnios
      recurred. Amnioinfused cases were compared to cases with pPROM and
      oligohydramnios who had standard management. RESULTS: The mean gestational age at
      first procedure was 22 weeks. The mean pre-procedure AFI was 1.1cm and post
      procedure was 12 cm. The mean number of infusions was 2.4. The mean first
      infusion to delivery interval was 33 days. The amnioinfused group when compared
      to the control group had decreased perinatal mortality of 33% versus 83%
      (P=0.036, OR=0.4, 95% CI=0.17-0.93), neonatal mortality of 17% versus 71%
      (P=0.049, OR=0.26, 95% CI=0.07-0.97) and neonatal sepsis 86% versus 27%(P=0.049,
      OR=0.32, 95% CI=0.12-0.87) with no statistical difference in gestational age at
      rupture and delivery nor birthweight. Babies discharged home compared to non
      survivors had a significant increase in gestational age at delivery, birthweight,
      NICU days and transabdominal amnioinfusions. Logistic regression showed that only
      transabdominal amnioinfusion and gestational age correlated with survival.
      CONCLUSION: In selected cases of oligohydramnios with pPROM, transabdominal
      amnioinfusions may be associated with fluid retention and improved neonatal
      survival.

PMID- 11950486
TI  - Cohort study of near-miss maternal mortality and subsequent reproductive outcome.
AB  - OBJECTIVE: To determine the aetiology and outcome of near-miss mortality in
      obstetrical patients and the subsequent reproductive outcome where fertility is
      conserved. STUDY DESIGN: Retrospective cohort study of 51,576 women delivered at
      a University teaching hospital of whom 50 required transfer for critical care.
      RESULTS: Over the 12 year study period 1988-1999, 50 women required transfer for
      intensive care (0.97/1000) and there were three maternal deaths (5.8/100,000).
      The main indications for transfer were hypertensive disease (32%), haemorrhage
      (24%) and maternal cardiac disease (24%). The perinatal mortality rate was 14%.
      Thirty two women conserved their fertility potential and 16 had subsequent
      healthy liveborn children. CONCLUSIONS: This study of near-miss maternal
      mortality reminds us of the need for continuing vigilance in the provision of
      obstetrical care. The successful reproductive outcome highlights the resilience
      of many women to adverse events in pregnancy but the high loss of fertility
      potential reflects the physical and psychological morbidity incurred.

PMID- 11950487
TI  - Comparison of GnRH agonists and antagonists in unselected IVF/ICSI patients
      treated with different controlled ovarian hyperstimulation protocols: a matched
      study.
AB  - OBJECTIVES: To evaluate the results of the use of GnRH antagonist (GnRHant) and
      GnRH analog (GnRHa) in two matched groups of unselected IVF/ICSI patients in a
      retrospective matched pair analysis. STUDY DESIGN: Patients (n=52) were
      stimulated with human menopausal gonadotropin (hMG) and/or recombinant FSH
      (rFSH). In Group I (n=26) a daily dose of 0.25mg of Cetrorelix (GnRHant) was
      administered when follicles reached a diameter of > or = 14 mm. Patients in Group
      II (n=26) were first desensitized with GnRHa triptorelin long protocol, which was
      continued during the gonadotropins treatment until the induction of ovulation.
      RESULTS: In both groups, serum LH levels remained low during the stimulation. The
      mean length of stimulation, and the dose of FSH required per patient were similar
      in both groups. The mean E2 level on day of hCG administration was significantly
      higher in the patients of Group II (2076+/-1430 versus 1145+/-605 pg/ml),
      however, a progressive increase in serum E2 concentration during the cycle was
      noted in both groups. A median of 5.38 and 6.34 mature oocytes per patient was
      obtained, and the fertilization rate was 59.3% in Group I and 63.6% in Group II.
      Pregnancy rate (PR) were better in Group II (15 versus 5%), and no severe or
      moderate ovarian hyperstimulation syndrome (OHSS) occurred. CONCLUSIONS: GnRHant
      and GnRHa provide comparable results in unselected patients, while GnRHant allows
      a higher flexibility in the treatment.

PMID- 11950488
TI  - In vitro fertilization in spontaneous cycles--our experience.
AB  - OBJECTIVE: To study the efficacy of a simple protocol of natural cycle in vitro
      fertilization. METHOD: A retrospective study of 59 natural treatment cycles in 37
      infertile couples with previous unsuccessful attempts of conventional in vitro
      fertilization. RESULTS: In 24% of cycles, the aspiration was cancelled because of
      inadequate visualization of follicles or because of preterm ovulation. Aspiration
      was performed in 45 cycles with oocyte retrieval of 82% per aspiration. Embryo
      transfer was performed in 30 cycles, pregnancy rate per pick-up was 15%.
      CONCLUSION: In vitro fertilization in a natural cycle is a simple, relatively
      cheap and comfortable procedure with reasonable results and can be offered to
      patients scheduled not only for in vitro fertilization because of tubal factor
      but also to patients with endometriosis or unexplained infertility.

PMID- 11950490
TI  - Is diminished pubocervical fascia collagen content a risk factor for failure of
      surgical management of genuine stress urinary incontinence in women?
AB  - OBJECTIVE: The assessment of relationship between pubocervical collagen content
      and clinical results of surgical treatment of genuine stress urinary incontinence
      (GSUI) in women. METHODS: Twenty-four women treated for genuine stress urinary
      incontinence were included into the study. All women underwent the same surgical
      procedure. The samples of pubocervical fascia were taken at the time of surgery.
      The contents of acid soluble, pepsin soluble, insoluble fraction of collagen,
      total collagen and collagen crosslinks were measured. The study of pubocervical
      fascia collagen metabolism included also estimation of collagenase activity. At
      follow-up done 5 years following surgery, 20 patients reported symptoms of GSUI
      (study group). Four women were still without symptoms of urine leakage (control
      group). RESULTS: The biochemical parameters of pubocervical fascia did not show,
      statistically significant differences between compared groups. CONCLUSION: The
      pubocervical fascia collagen metabolism does not have impact on the results of
      anti-incontinence surgery.

PMID- 11950489
TI  - Synergistic inhibitory effects of genistein and tamoxifen on human dysplastic and
      malignant epithelial breast cells in vitro.
AB  - OBJECTIVE: Genistein is a phytoestrogen with in vitro anticancerogenic activity.
      We examined in vitro the effects of genistein alone, or in combination with
      estradiol and tamoxifen, on the growth of human dysplastic and malignant
      epithelial breast cell lines. METHODS: Dysplastic breast cell lines (MCF-10A(1),
      MCF-ANeoT, MCF-T(6)3B) and cell lines of breast cancer (MCF-7, MDA-231, MDA-435)
      were cultured as monolayers in RPMI 1640 medium supplemented with 10% fetal
      bovine serum, and L-glutamine. After preincubation of 20 h, genistein (1, 2.5, 5,
      7.5 and 10 microg/ml) alone or in combination with estrogen or tamoxifen was
      added to the cultured cells. The cells were treated continuously for 72 h and
      then the growth rate was assessed colorimetrically. Stepwise multiple linear
      regression analysis was used to evaluate the effect of genistein, tamoxifen, and
      estradiol on cell proliferation. RESULTS: Genistein had a significant (dose
      dependent) inhibitory effect on the proliferation of both dysplastic (P<0.0001)
      and malignant (P<0.0001) cells. The growth inhibition was significantly higher
      P<0.0001 in dysplastic cells compared to the cancer cells. Addition of tamoxifen
      to genistein further inhibited the proliferation of both cell types, reflecting a
      synergistic antiproliferative effect on dysplastic cells P<0.0001 and an additive
      growth inhibition effect P<0.0003 on malignant cells. Estradiol significantly
      (P=0.005) stimulated the growth of dysplastic cell lines while a significant
      (P=0.003) antiproliferative effect on growth of the malignant cells was observed.
      The concentration of estrogen receptor (ER) had no significant effect on growth
      rates and did not modulate the effects of genistein or tamoxifen. CONCLUSIONS:
      Genistein (1-10 microg/ml) inhibits the growth of dysplastic and malignant
      epithelial breast cancer cells in vitro and the addition of tamoxifen (10(-6),
      10(-7)M) has a synergistic/additive inhibitory effect. These effects are not
      modulated by the presence of ER.

PMID- 11950491
TI  - Effect of different doses of progestin on uterine leiomyomas in postmenopausal
      women.
AB  - OBJECTIVE(S): To evaluate the effects of two doses of medroxyprogesterone acetate
      (MPA) on uterine leiomyoma sizes and on uterine bleeding pattern in
      postmenopausal women treated with oral hormone replacement therapy (HRT). STUDY
      DESIGN: Thirty natural postmenopausal women affected by uterine leiomyomas were
      enrolled and treated with oral micronized estradiol (E(2)) at dose of 2 mg per
      day, and randomized to receive in association MPA at dose of 2.5 mg daily (group
      A) or of 5 mg daily (group B). At the beginning of the study and after 1 year of
      treatment, uterine leiomyomata dimensions were measured using transvaginal
      ultrasonography (TV-USG). The subjects were instructed to note on a daily dairy
      the number and severity of abnormal uterine bleeding (AUB) episodes. RESULTS:
      After 1 year of therapy, a significant changes in mean uterine leiomyomas size
      was observed in the group treated with higher dose of MPA. No significant
      differences in uterine bleeding were detected between the two groups.
      CONCLUSION(S): In postmenopausal women with uterine leiomyomas, it is necessary
      to use the minimal efficacious dose of progestin during HRT because of a higher
      risk to increase the tumors dimensions.

PMID- 11950492
TI  - Thirty-day postoperative mortality after hysterectomy in women with liver
      cirrhosis: a Danish population-based cohort study.
AB  - BACKGROUND: Women with liver cirrhosis have a higher incidence of hysterectomy
      than the general population, generally because of abnormal bleeding. They may
      also have an increased risk of postoperative mortality and morbidity. METHODS: In
      the nationwide Danish National Patients Register (NPR) we identified all women
      diagnosed with liver cirrhosis from 1977 to 1993. From this cohort we selected
      all women undergoing hysterectomy. A random sample of women without liver
      cirrhosis undergoing hysterectomy was selected as controls. Outcome was defined
      as mortality within the first 30 days after discharge. Logistic regression
      analysis was used to estimate the association between liver cirrhosis and 30-day
      postoperative mortality, adjusted for age, comorbidity, and type of admission.
      RESULTS: Out of 8539 women with liver cirrhosis 105 underwent hysterectomy. We
      found a 30-day postoperative mortality of 7.6% (95% confidence interval (CI) 2.5
      12.7%) and 0.6% (95% CI 0.5-0.7%) in women with and without liver cirrhosis,
      respectively. The crude odds ratio was 14 (95% CI 6.5-29) and the adjusted odds
      ratio was 11 (95% CI 4.8-24) for 30-day postoperative mortality in women with
      liver cirrhosis compared with non-cirrhotic controls. CONCLUSION: Hysterectomy in
      women with liver cirrhosis is associated with an 11-fold increased risk of death
      within the first 30 days after discharge.

PMID- 11950493
TI  - Vulval squamous cell carcinoma arising in localized Darier's disease.
AB  - Darier's disease (keratosis follicularis) is a rare vulval lesion and it has been
      associated with squamous and non-squamous tumors from different origin. A vulval
      squamous cell carcinoma (SCC) arising in a localized Darier's disease is
      presented. To our knowledge, this is the first case to report the association of
      a vulval SCC and a localized Darier's disease. The possibility of delaying or
      overlooking the diagnosis of a vulval carcinoma is also illustrated. It is
      suggested to resect the whole lesion of Darier's disease localized to the vulva
      or take multiple biopsies.

PMID- 11950494
TI  - Rupture of rudimentary horn pregnancy at the 15th week of gestation: a case
      report.
AB  - A patient with acute abdomen at 15th week of gestation underwent an emergency
      laparatomy. A ruptured rudimentary horn pregnancy was diagnosed, and the
      rudimentary part including the fetus and the accessories was resected. The mother
      survived without any complications.

PMID- 11950495
TI  - Successful medical management of multifocal psoas abscess following cesarean
      section: report of a case and review of the literature.
AB  - The psoas abscess is a rare complication in obstetric and gynaecology. Two types
      of psoas abscess are recognized. The primary psoas abscess is generally following
      haematogenous dissemination of an infectious agent and the source is usually
      occult. The most frequently isolated pathogen is Staphylococcus aureus. On the
      other hand, the secondary abscess is the result of local extension of an
      infectious process near the psoas muscle. We report the case of a patient who
      develops a bacteremia from an infected cesarean section wound. The complications
      were thigh and psoas abscesses with left sacroiliitis. Medical management with
      prolonged antibiotherapy permit clinical, biological and radiological
      improvement. Although it required a long hospital stay, medical treatment alone
      was effective. More experience is required to determine which therapeutic option:
      medical treatment and/or surgery, is the best choice for this type of
      complication.

PMID- 11950496
TI  - Surgery of a splenic artery aneurysm during pregnancy.
AB  - We report a case of ligation of the splenic artery with splenectomy during
      pregnancy due to a splenic artery aneurysm. The risk of aneurysmal rupture is
      increased in multipara and during pregnancy. As a result of high maternal and
      fetal morbidity and mortality elective surgery should be performed.

PMID- 11950497
TI  - Raynaud's syndrome of the nipple in pregnancy.

PMID- 11950499
TI  - The fate of biodegradable microspheres injected into rat brain.
AB  - Biodegradable microspheres made with poly-[D,L-lactide-co-glycolide] represent an
      evolving technology for drug delivery into the central nervous system. Even
      though these microspheres have been shown to be engulfed by astrocytes in vitro,
      the purpose of the present study was to track the fate of biodegradable
      microspheres in vivo. This was accomplished using microspheres containing the
      fluorescent dye coumarin-6 followed 1 day, 1 week and 1 month after intracerebral
      injections of this material were made into the rat brain. Using dual color
      immunohistochemistry and antisera against glial fibrillary acidic protein for
      astrocytes versus phosphotyrosine for microglia, results demonstrate that
      phagocytosis of small coumarin-containing microspheres <7.5 microm in diameter
      was primarily by microglia in vivo during the first week post-injection. In
      contrast, only a small minority of these microspheres appeared to be engulfed by
      astrocytes.

PMID- 11950500
TI  - Respiratory function in mice lacking or overexpressing the prion protein.
AB  - We investigated a possible involvement of the prion protein in ventilatory
      control in four groups of mice, those deficient for the prion protein (PrP(c)),
      those overexpressing the prion protein, and two groups of genetically and age
      matched controls. Ventilatory patterns of unrestrained mice were measured in a
      whole-body plethysmograph. Between each genotype and its control, we compared
      ventilation at rest and the ventilatory response to moderate hypoxia (10-12% O2),
      hyperoxia and hyperoxic hypercapnia. Mice lacking or overexpressing PrP(c) and
      their respective controls showed similar ventilatory patterns at rest and similar
      chemosensory responses when awake and under urethane anesthesia. Our results do
      not support the view that PrP(c) may play any significant role in basal
      ventilation or in the chemosensory ventilatory control of adult mice.

PMID- 11950501
TI  - The effect of orexin-A and -B on the histamine release in the anterior
      hypothalamus in rats.
AB  - The neuropeptides orexin-A and -B have been reported to be appetite-stimulating
      peptides, but they are also known as important factors that control arousal
      state. We studied the effects of orexin-A and -B on the hypothalamic histamine
      release using in vivo microdialysis. A significant and sustained increase in
      histamine release was observed by intracerebroventricular injection of 1 nmol of
      orexin-A, but not by the same dose of orexin-B. An increased dose of orexin-B to
      5 nmol facilitated histamine release, although this effect was much less potent
      than orexin-A. These findings suggest that both of the orexins play important
      roles in the regulation of waking through the activation of histaminergic system.

PMID- 11950502
TI  - Limited intercellular spread of spontaneous Ca2+ signals via gap junctions
      between mouse chromaffin cells in situ.
AB  - Using a confocal laser-scanning microscope, we measured the changes in the
      cytosolic Ca(2+) concentration ([Ca]i) of chromaffin cells on adrenal slice
      preparations of mouse. The spontaneous fluctuations of [Ca]i were often observed
      in situ, as reported in isolated rat and bovine cells. Intriguingly, the
      spontaneous [Ca]i changes in one cell were often transmitted to one or two
      adjacent cells, and the synchronized [Ca]i changes were often observed in two
      adjacent cells, both of which failed to respond to ATP. The synchronized [Ca]i
      changes between two cells were much less frequently observed in rat than in mouse
      adrenals. The spontaneous [Ca]i changes were also synchronized between closely
      touching mouse chromaffin cells in culture. These results suggest that the spread
      of Ca(2+) signaling is mediated by low-conductance intercellular coupling.

PMID- 11950503
TI  - Cortical sensorimotor alterations in Unverricht-Lundborg disease patients without
      generalized seizures.
AB  - We investigated cortical functions of two Unverricht-Lundborg disease (ULD)
      patients suffering from myoclonic jerks, but no generalized tonic-clonic
      seizures. Somatosensory cortical responses were recorded to median nerve stimuli
      and coherence was calculated between cortical and muscle signals during isometric
      contraction of hand muscle. In contrast to ULD patients with generalized tonic
      clonic seizures, responses of the primary somatosensory (SI) cortex were only
      slightly enhanced in the left and normal in the right hemisphere, and no early
      responses were observed in the ipsilateral SI. Cortex-muscle coherence was
      remarkably enhanced. We conclude that in ULD patients without generalized tonic
      clonic seizures, both the excitability of the SI and transcallosal conduction are
      relatively normal, probably decreasing susceptibility to generalized seizures.
      Disturbed cortical control of muscle contraction indicates selective alteration
      of the motor cortex activation.

PMID- 11950504
TI  - 5-HT2A receptor gene polymorphism and eating disorders.
AB  - Recent studies have reported a genetic association between the -1438 G/A
      polymorphism within the promoter region of the 5-HT(2A) receptor gene and eating
      disorders (ED), with conflicting results. To clarify the role of the -1438 G/A
      polymorphism in different ED categories we have analyzed the genotype and allele
      frequency distribution in 54 Italian patients with Binge ED (BED) compared to 132
      obese non-BED subjects. No significant differences were found between obese BED
      and obese non-BED individuals, suggesting that this polymorphism does not
      genetically distinguish these two phenotypes. Moreover, the evaluation of 148
      patients with anorexia nervosa and 86 patients with bulimia nervosa revealed an
      association of the A allele with both these disorders.

PMID- 11950505
TI  - Nerve growth factor induces angiogenic activity in a mouse model of hindlimb
      ischemia.
AB  - Recent studies suggest that nerve growth factor (NGF), a neurotrophic factor
      known to play a crucial role in neurite growth and differentiation, may also
      modulate vascular cell functions. In the present study, it was investigated
      whether NGF exhibits an angiogenic effect in a mouse model of hindlimb ischemia
      induced by femoral artery occlusion. Enzyme-linked immunosorbent assay
      determination revealed an enhanced endogenous NGF production (378 +/- 100 and 54
      +/- 26 pg/g tissue in 7 day ischemic and normoperfused adductor muscles,
      respectively; P<0.05). Furthermore, exogenous NGF, administered subcutaneously
      for 7 days in ischemic hindlimb, induced a marked increase of arteriole length
      density (NGF =41 +/- 5 vs. Saline=22 +/- 4 mm/mm(3); P<0.05). However,
      capillaries were not significantly increased (NGF =1035 +/- 182 vs. Saline= 829
      +/- 60 mm/mm(3); P>0.05). In conclusion, the present study provides first
      evidence that NGF exerts angiogenic properties in vivo.

PMID- 11950506
TI  - Contrasting behavior of beta event-related synchronization and somatosensory
      evoked potential after median nerve stimulation during finger manipulation in
      man.
AB  - Electrical median nerve stimulation during rest results in two cortical
      responses: the somatosensory evoked potential (SEP); and the induced beta
      oscillations (beta event-related synchronization (ERS)). Both types of responses
      were recorded with electroencephalography and studied during rest and motor
      behavior in eight normal subjects. During manipulation of a cube with the fingers
      of the right hand, the beta ERS around 20 Hz, induced by right hand median nerve
      stimulation, is significantly suppressed, whereas the long-latency SEP components
      are significantly enhanced. The results suggest that both phenomena can be
      interpreted as responses of different neuronal structures in sensorimotor areas.

PMID- 11950507
TI  - Rats with chronic spinal cord transection as a possible model for the at-level
      pain of paraplegic patients.
AB  - Patients with complete spinal cord injury (SCI) often suffer from chronic pain
      which is perceived around the segment of the lesion. The present study tests the
      hypothesis that chronic SCI pain is due to pathophysiological neuronal activity
      in the spinal segment just rostral to the SCI. In an animal model with complete
      chronic SCI, the impulse activity of single dorsal horn neurones was recorded in
      the segment rostral to the lesion. Following SCI, the neurones exhibited a higher
      background activity. Some neurones showed an abnormal type of activity which was
      not present under control conditions. The results support the hypothesis that
      increased and altered background activity just rostral to the lesion contributes
      to chronic at-level pain of paraplegic patients.

PMID- 11950508
TI  - Electrophysiological evidence that a set of interfascicular cells of the rat
      anterior commissure are neurons.
AB  - In mammals, the anterior commissure (AC) provides a route that interconnects
      homonymous areas of the basal forebrain. Recently, we reported the presence of
      short-axon and projection neurons among the axonal fascicles of the rat AC (i.e.
      interfascicular neurons; IFNs). This, coupled with the commissural inputs to
      these neurons, suggests that in addition to conveying nerve impulses, the AC may
      be a site of neural processing. To test this hypothesis, the electrophysiological
      activity of IFNs was recorded in adult albino rats. From extracellular recordings
      performed in 11 IFNs, it was found that these cells: (1), have a spontaneous
      discharge of a relatively low frequency (i.e. 0.04 +/- 0.1 to 5.9 +/- 3.2 spikes
      per second); (2), application of anodic current in the adjacent commissural
      fibers decreased this frequency; and (3), application of cathodic current
      increased the number of action potentials. Since observations made in Golgi
      impregnated sections suggest that the main input to IFNs arises from their
      commissural collaterals, it is concluded that these cells may participate in the
      integration of interhemispheric nerve impulses.

PMID- 11950509
TI  - Changes in three subtypes of tetrodotoxin sensitive sodium channel expression in
      the axotomized dorsal root ganglion in the rat.
AB  - The upregulated expression of tetrodotoxin sensitive (TTXs) Na+ channels is
      thought to play an important role in the development of ectopic discharges (EDs)
      in axotomized sensory neurons. The present study examined the levels of mRNAs of
      three subtypes of TTXs Na(+) channels, Na(v)1.7, Na(v)1.6, and Na(x), in the
      dorsal root ganglion (DRG) after segmental spinal nerve ligation. Following nerve
      ligation, the level of mRNAs of Na(v)1.7 and Na(v)1.6 was decreased, while the
      Nax mRNA level was increased at 5 days, but not at 1 day, postoperatively
      compared with the normal levels. Thus, if upregulated expression of TTXs Na+
      channels contributes to the generation of EDs in axotomized DRG neurons, Na(x) is
      the most likely contributor among the three tested subtypes.

PMID- 11950510
TI  - Inflammatory pain mediated by a phenotypic switch in brain-derived neurotrophic
      factor-immunoreactive dorsal root ganglion neurons innervating the lumbar facet
      joints in rats.
AB  - Human low back pain sometimes originates from lumbar facet joints. In human
      lumbar facet joint inflammation or degeneration, the referred pain is not only
      expanded into the low back area but also into the leg or foot. The rat L5-L6
      facet joint is innervated by the L1-L5 dorsal root ganglia. The presence of brain
      derived neurotrophic factor-immunoreactive dorsal root ganglion neurons
      innervating the L5-L6 facet joint has been confirmed, but changes in the number
      and distribution of these neurons caused by inflammation have not been studied.
      Of fluorogold-labeled neurons innervating the L5-L6 facet joint, the proportion
      of brain-derived neurotrophic factor-immunoreactive dorsal root ganglion neurons
      was 16% in the control group and 26% in the inflammatory group. The proportion of
      brain-derived neurotrophic factor-immunoreactive dorsal root ganglion neurons
      labeled by fluorogold was significantly higher in the inflammatory group than in
      the control group (P<0.05). The mean cross-sectional area of fluorogold-labeled
      brain-derived neurotrophic factor-immunoreactive cells increased from 580 to 915
      microm(2) in the inflammatory group (P<0.01). Associated with inflammation in
      facet joints, the increase of brain-derived neurotrophic factor-immunoreactive
      neurons and the phenotypic switch to large neurons may induce the expansion of
      facet joint inflammatory pain.

PMID- 11950511
TI  - Developmental changes and localization of mouse brain serine proteinase mRNA and
      protein in mouse brain.
AB  - Serine proteases are known to be involved in neural development and various
      functions in the central nervous system. Mouse brain serine proteinase (mBSP) is
      expressed almost exclusively in the mouse brain and it has been characterized at
      the molecular and biochemical levels. In this study, we analyzed the
      developmental changes and localization of mBSP mRNA and protein in the mouse
      brain, using reverse transcription-polymerase chain reaction, Western blotting,
      and immunohistochemistry. Expression of mBSP was strong in the white matter and
      the nerve tracts after postnatal day 30, especially in the cerebellum and the
      medulla oblongata. These results suggest that mBSP contributes to development and
      sustaining the functions in the mouse brain.

PMID- 11950512
TI  - Psychogenic sensory loss: magnetic source imaging reveals normal tactile evoked
      activity of the human primary and secondary somatosensory cortex.
AB  - We investigated the activation of the secondary somatosensory cortex (SII) in
      three patients with unilateral psychogenic sensory loss in the hand.
      Somatosensory evoked magnetic fields were recorded in response to tactile
      stimulation of the index finger of the affected and the unaffected hand. Brain
      sources were estimated by magnetic source imaging. In all subjects, responses in
      both the contralateral primary somatosensory (SI) and bilateral SII areas were
      normal as compared with a healthy control group, irrespective of the stimulated
      side. The results extend previous findings of normal evoked activity in SI.

PMID- 11950513
TI  - GABAergic pretectal terminals contact GABAergic interneurons in the cat dorsal
      lateral geniculate nucleus.
AB  - Anterograde tracing techniques combined with postembedding immunocytochemical
      staining were used to determine the gamma amino butyric acid (GABA) content of
      pretectogeniculate (PT-LGN) terminals and their postsynaptic targets. The results
      provide evidence that PT-LGN terminals are GABAergic and that they contact
      GABAergic interneurons. These results corroborate previous anatomical studies and
      support the idea that the PT-LGN projection functions to disinhibit
      thalamocortical cells in the dorsal lateral geniculate nucleus.

PMID- 11950514
TI  - Neurokinin NK1- and NK3-immunoreactive neurons in serotonergic cell groups in the
      rat brain.
AB  - Interactions are known to occur in the brain between serotonin (5-HT) and
      substance P (SP). To investigate whether SP can directly influence serotonergic
      neurons, double immunohistochemical labelings were performed on rat brain
      sections with NK1 or NK3 affinity-purified antibodies and a 5-HT monoclonal
      antibody. It was found that the vast majority of serotonergic cell bodies do not
      colocalize NK1 or NK3 labeling. Only in the central linear nucleus and ventral
      part of the dorsal raphe nucleus were a few serotonergic neurons double-labeled
      for NK1 receptors (15 and 0.8% of serotonergic neurons, respectively). It is
      suggested that serotonergic neurons are not major direct targets for SP in the
      rat brain.

PMID- 11950515
TI  - Ankyrin G and voltage gated sodium channels colocalize in human neuroma--key
      proteins of membrane remodeling after axonal injury.
AB  - We tested if ankyrin G could be detected in human neuroma, if it colocalized with
      site-specific peripheral nerve sodium channels that accumulate at axon tips of
      injured nerve, and if there are differences in the distribution of these proteins
      in non-painful neuroma and painful neuroma tissue vs. normal nerve. Frozen
      sections from one painful, six non-painful, and three normal nerves were
      immunocytochemically examined. A double labeling technique with highly specific
      antibodies against peripheral nerve type 1 (Na(v)1.7), and peripheral nerve type
      3 (Na(v)1.8) sodium channels and anti-ankyrin G antibodies detected sodium
      channels and ankyrin G on the same section, using confocal laser scanning
      microscopy. Ankyrin G colocalized with both types of sodium channels. Neuroma
      specimens exhibited considerably larger immunofluorescence for both sodium
      channels and ankyrin G compared with normal nerve. The painful neuroma presented
      an even more pronounced immunolabeling in clusters. Findings support results from
      animal models that link ankyrin G with clustering of sodium channels at axon tips
      of unmyelinated, sprouting fibers. A common (repair-) mechanism that exists
      throughout the human nervous system for clustering sodium channels at a high
      density is assumed. A dysregulation in this membrane remodeling mechanism might
      be an initial step in a cascade that leads to a painful rather than a non-painful
      neuroma.

PMID- 11950516
TI  - Topographic segregation and convergence of verbal, object, shape and spatial
      working memory in humans.
AB  - This functional magnetic resonance imaging study investigates commonalties and
      differences in working memory (WM) processes employing different types of
      stimuli. We specifically sought to characterize topographic convergence and
      segregation with respect to prefrontal cortex involvement using verbal, spatial,
      real object and shape memory items in a two-back WM task. Both the dorsolateral
      and ventrolateral prefrontal cortices are conjointly activated across all
      stimulus types. No stimulus-specific differences in the activation patterns of
      the prefrontal cortex could be demonstrated giving support to the view of an
      amodal prefrontal involvement during WM processes. However, extra-frontal regions
      specialized on feature processing and involved in the preprocessing of the
      stimuli were selectively activated by these different subtypes of WM. These
      selectively activated regions are assigned to parts of the ventral and dorsal
      stream.

PMID- 11950517
TI  - The effect of IL4 +33C/T polymorphism on risk of Japanese sporadic Alzheimer's
      disease.
AB  - Interleukin-4 (IL4) is an anti-inflammatory cytokine that may play a role in the
      inflammation pathology observed surrounding senile plaques, and may also
      associate with Alzheimer's disease (AD) pathogenesis. Recently, it has been
      reported that a single nucleotide polymorphism in the IL4 gene promoter region,
      IL4 +33C/T polymorphism, associates with its phenotype. It was thought that the
      IL4 +33C/T polymorphism causing high IL4 production may reduce the risk for AD.
      In the present study, therefore, we investigated this mutation in 108 healthy
      controls and in 178 sporadic AD cases by the polymerase chain reaction
      restriction fragment length polymorphism method in a Japanese AD population.
      Allelic frequencies with +33C/T polymorphism in the gene were 35.6 and 32.6% in
      the control and AD groups, respectively. Our results failed to demonstrate an
      association between this polymorphism and Japanese sporadic AD. We also tested
      whether the IL4 functional variants were regulated by this polymorphism in a
      portion of the subjects (16 AD cases and 13 control cases). We could not find any
      relationship between the IL4 +33C/T polymorphism and plasma IL4 concentration.

PMID- 11950518
TI  - Modulation of kappa-opioidergic systems on mecamylamine-precipitated nicotine
      withdrawal aversion in rats.
AB  - The present study was designed to examine the modulation of the kappa-opioidergic
      system on mecamylamine-precipitated nicotine-withdrawal aversion. The nicotinic
      receptor antagonist mecamylamine, which is known to pass the blood-brain barrier,
      produced a place aversion in rats chronically treated with nicotine using an
      osmotic mini-pump. This effect was significantly attenuated by pretreatment with 
      opioid receptor agonists U50,488H (1.0 mg/kg, s.c.) and TRK-820 (0.03 mg/kg,
      s.c.). The attenuation of mecamylamine-precipitated nicotine-withdrawal aversion
      by U50,488H was completely reversed by the combination with a selective -opioid
      receptor antagonist nor-binaltorphimine (10.0 mg/kg, i.p.). These results suggest
      that the activation of endogenous -opioidergic systems can suppress the
      mecamylamine-precipitated nicotine-withdrawal aversion.

PMID- 11950519
TI  - The effects of laminin-1 on spiral ganglion neurons are dependent on the MEK/ERK
      signaling pathway and are partially independent of Ras.
AB  - Laminin-1 (LN) is expressed along the route of neural growth from spiral ganglion
      (SG) neurons towards the developing organ of Corti, and has been shown to enhance
      neurite outgrowth from SG neurons in vitro. Signal transduction pathways linking
      LN signaling at the cell membrane to the cell nucleus can involve a variety of
      signaling molecules. Data from other systems suggest the potential involvement of
      the small G protein Ras, and the mitogen-activated protein kinases (MAPKs) Erk
      and/or p38. To assess these possibilities, the length and number of processes
      extending from SG explants cultured on LN-coated surfaces were evaluated after
      treatment with the Ras inhibitor FTI-277, the p38 inhibitor SB203580 and MAPK
      kinase (MEK) inhibitor U0126, which operates immediately upstream of the Erk
      MAPK. Treatment with the Ras inhibitor at levels known to inhibit the H- and N
      Ras isoforms had no effect, while FTI-277 levels known to inhibit K-Ras reduced
      only neurite length. Suppression of MEK resulted in a decrease of both
      parameters, while incubation with the p38 inhibitor had no effect. The results of
      this study suggest that MEK plays a central role in LN signaling in SG neurites.
      While K-Ras signaling may participate in MEK-dependent increases in neurite
      length, the MEK-dependent increase in neurite number appears to be activated by a
      different intracellular pathway.

PMID- 11950520
TI  - Effect of noise exposure on blood-labyrinth barrier in guinea pigs.
AB  - The influence of noise exposure on the endothelial transport system in the
      cochlea was investigated using cationic polyethyleneimine (PEI), since
      systemically administered PEI passes through the capillary endothelial cell and
      attaches to basal lamina (BL) anionic sites in the cochlea. Under general
      anesthesia, all guinea pigs were administered an intravenous injection of 0.5%
      PEI. Thirty minutes later, five animals were exposed to noise (10 kHz, broad band
      noise, 105 dB SPL) for 30 min, via speakers inserted into the external auditory
      canal. The remaining five animals (controls) were left without noise exposure for
      1 h following PEI injection. All guinea pigs were then immediately sacrificed,
      and the bony labyrinths were removed. PEI distribution on the BL was assessed in
      the stria vascularis, spiral ligament, basilar membrane, spiral limbus and
      Reissner's membrane throughout the cochlea with transmission electron microscopy.
      Compared to control animals, PEI distribution in the noise-exposed animals was
      significantly increased in the strial vessels of the basal and second turns and
      in Reissner's membrane of all turns. In the spiral ligament, basilar membrane and
      spiral limbus, no significant difference in PEI distribution was observed between
      the control and noise-exposed animals. These findings indicate that noise
      exposure increases macromolecular transport in the stria vascularis but not in
      the spiral ligament, spiral limbus and basilar membrane and that systemically
      administered macromolecules are more readily transported to Reissner's membrane
      by noise exposure.

PMID- 11950521
TI  - Nucleus magnocellularis and nucleus laminaris in Belgian Waterslager and normal
      strain canaries.
AB  - Belgian Waterslager (BWS) canaries are characterized by a mean 30% loss of hair
      cells in the basilar papilla compared to other canaries, and a corresponding
      increase in behavioral auditory thresholds. In spite of the large number of
      missing and damaged sensory cells, there is on average only a 12% reduction in
      the number of fibers in the VIIIth nerve. In this study, we examined cell number
      and size, and volume of auditory nuclei, specifically in nucleus magnocellularis
      and nucleus laminaris in Belgian Waterslager canaries. While the overall
      anatomical structure and organization of these nuclei and the total number of
      cells in the non-BWS and BWS canaries were comparable, BWS canaries showed a
      significant decrease in the volume of the auditory nuclei that was attributed to
      a reduction in cell size. These results provide further evidence in favor of a
      role of the sensory epithelium in the maintenance of central auditory structures.

PMID- 11950523
TI  - The effect of noise bandwidth on the contralateral suppression of transient
      evoked otoacoustic emissions.
AB  - The purpose of this study was to determine whether the bandwidth or loudness of a
      contralateral stimulus is the most important factor in evoking suppression of
      transient evoked otoacoustic emissions (TEOAEs). TEOAEs were measured in both
      ears of 10 women in quiet and in the presence of one of three contralateral noise
      bands; narrow band (NB), wide band (WB) and equalized (EQ), all centered at 2000
      Hz. The NB (100 Hz bandwidth) and WB (2200 Hz bandwidth) noises were presented at
      60 dB SPL. The SPL of the EQ (100 Hz bandwidth) noise was adjusted such that it
      was equal in loudness to the WB noise as determined using a psychoacoustic
      procedure. Only the WB noise was associated with a significant reduction of TEOAE
      levels. It is believed that this effect occurred because the WB noise has greater
      effective energy representation across frequency on the basilar membrane as it
      may receive more gain from the action of the cochlear amplifier. Results of the
      present study indicate that noise bandwidth is the most important factor in the
      contralateral suppression of TEOAEs.

PMID- 11950522
TI  - Oxidative DNA damage is associated with intense noise exposure in the rat.
AB  - Increasing evidence suggests that noise-induced hearing loss may be reduced or
      prevented with antioxidant therapy. Biochemical markers of reactive oxygen
      species (ROS)-induced damage can help elucidate possible treatment timing
      constraints. This study examined the time course of ROS damage following a 2-h,
      broad-band noise exposure resulting in permanent threshold shift in 35 Long-Evans
      rats. Cochlea, brain, liver, serum and urine were analyzed at 1, 3, 8, 72, and
      672 h (28 days) after exposure. Oxidative DNA damage was assessed by measuring 8
      hydroxy-2'-deoxyguanosine (8OHdG) by high performance liquid chromatography with
      electrochemical detection. Lipid peroxidation was measured via the thiobarbituric
      acid-reactive substances (TBARS) colorimetric assay for detection of aldehydes
      (e.g., malondialdehyde). Auditory brainstem response and distortion product
      otoacoustic emission thresholds showed progressive elevation for the 3- and 8-h
      groups, then notable recovery for the 72-h group, and some worsening for the 672
      h group. 8OHdG was significantly elevated in cochlea in the 8-h group, and in
      brain and liver for the 72-h group. TBARS were significantly elevated in serum
      for the 72-h group. Based upon oxidative DNA damage present in cochlea following
      intense noise, we postulate that the first 8 h following exposure might be a
      critical period for antioxidant treatment.

PMID- 11950525
TI  - Effects of acoustic trauma on dorsal cochlear nucleus neuron activity in slices.
AB  - Previous studies found increased multi-unit spontaneous activity in the dorsal
      cochlear nucleus (DCN) of animals that had been exposed to intense sound. Such
      activity may be related to tinnitus. Our study examined effects of previous
      exposure to intense sound on single neurons in the DCN, by measuring spontaneous
      activities and sensitivities to acetylcholine, an important neurotransmitter of
      centrifugal pathways to the cochlear nucleus, in brain slices. Spontaneous
      discharges were recorded extracellularly in the DCN portion of brain slices from
      control and intense-tone-exposed rats. Slices from exposed rats showed increased
      prevalence of bursting and decreased regular spontaneous activity. Since regular
      neurons include fusiform cells, and bursting neurons include cartwheel cells,
      intense tone exposure may lead to increased activity of DCN cartwheel cells and
      decreased activity of fusiform cells. Alternatively, the activity of some
      fusiform cells might change to bursting. Intense tone exposure also appeared to
      increase bursting neuron sensitivity to carbachol. This suggests that changes in
      DCN cartwheel cell spontaneous activity may reflect changes in effects of
      cholinergic centrifugal pathways following intense tone exposure. We conclude
      that acoustic trauma may lead to changes in the physiology and pharmacology of
      DCN neurons. These changes may be related to underlying mechanisms of central
      tinnitus.

PMID- 11950524
TI  - The electrochemical and fluorescence detection of nitric oxide in the cochlea and
      its increase following loud sound.
AB  - A nitric oxide (NO)-selective sensor (tip diameter 30 microm) was inserted into
      the perilymph of the basal turn of the guinea pig cochlea. The basal level and
      stimulation-induced changes of NO were measured. The mean (+/-S.E.M.) basal level
      of NO was 273+/-42.9 nM. Following perilymphatic perfusion of the artificial
      perilymph containing NO synthase (NOS) substrate L-arginine (100 microM) combined
      with cofactor (6R)-5,6,7,8-tetrahydrobiopterin dihydrochloride (100 microM), a
      rapid and significant increase of NO to a mean concentration of 392+/-32.3 nM (P
      < 0.01, n = 10) was recorded. In contrast, a significant decrease of mean NO
      concentration to 180+/-32.7 nM (P < 0.01, n = 10) was observed following the
      perfusion of the NOS-inhibiting agent N(G)-nitro-L-arginine methyl ester (100
      microM). No change in the NO concentration was found following the perfusion of
      either artificial perilymph or N(G)-monomethyl-D-arginine (100 microM) solution
      employed as controls. Broadband noise exposure (3 h/day at 120 dBA SPL) for three
      consecutive days produced an increase in NO concentration to 618+/-60.7 nM (P <
      0.05, n = 10) in the perilymph. In addition, by using specific dyes for NO, 4,5
      diaminofluoresceine diacetate and for the reactive oxygen species (ROS),
      dihydrorhodamine 1,2,3, the distribution of NO in the whole mounts of the organ
      of Corti and the production of ROS in vivo in the organ of Corti were
      investigated in both control (n = 5) and noise-exposed (n = 5) animals. The more
      intense NO and ROS fluorescence was observed in both the inner and outer hair
      cells in the noise-exposed groups. It is proposed that both the basal level and
      the increase in NO concentration following the addition of substrate (L-arginine)
      are produced by the constitutive NOS while the elevated NO and ROS following
      noise exposure indicate that NO may be involved in noise-induced hearing loss.

PMID- 11950526
TI  - An estimate of the auditory-filter bandwidth in the Mongolian gerbil.
AB  - Critical ratios (CRs) and the critical band (CB) were determined in six Mongolian
      gerbils (Meriones unguiculatus) using a GO/NOGO procedure and the method of
      constant stimuli. The test-tone frequencies were 0.5, 1, 2, 4 and 8 kHz in the CR
      measurements and 2 kHz in the CB measurement. Critical ratios were independent of
      the level of the white-noise masker. The lowest CR with a mean of 24.8 dB was
      found at 1 kHz for maskers with spectrum levels of 20 and 40 dB SPL. The CR
      increased on average by 2.1 dB per octave between the frequencies 1 and 4 kHz.
      The CR bandwidth at 2 kHz and at a masker spectrum level of 40 dB SPL was 417 Hz.
      Using the band-narrowing procedure, we determined a mean CB of 216 Hz at a test
      tone frequency of 2 kHz. The results are discussed in comparison to
      psychophysical data from other rodent species and humans. Finally, the relation
      of CR and CB bandwidths to the bandwidth of tuning curves of gerbil auditory
      nerve fibers and the gerbil's cochlear frequency map are explored.

PMID- 11950527
TI  - 5-HT(1A) receptor subtype mRNA expression in cochlear nucleus.
AB  - Previous studies indicate expression of various serotonin receptor subtypes,
      including the 5-HT(1A) receptor subtype, in rodent cochlear nucleus. Our long
      term goal is to identify the types of cochlear nucleus neurons, which are well
      described in cat, that express 5-HT receptors. In the current study, the reverse
      transcriptase/polymerase chain reaction and the in situ hybridization method were
      used to detect the mRNA encoding a portion of the 5-HT(1A) receptor subtype in
      the cochlear nucleus of the cat.

PMID- 11950528
TI  - The effects of chronic intracochlear electrical stimulation on inferior
      colliculus spatial representation in adult deafened cats.
AB  - Previous studies have shown that chronic electrical stimulation through a
      cochlear implant causes significant alterations in the central auditory system of
      neonatally deafened cats. The goal of this study was to investigate the effects
      of chronic stimulation in the mature auditory system. Normal hearing adult
      animals were deafened by ototoxic drugs and received daily electrical stimulation
      over periods of 4-6 months. In terminal physiology experiments, response
      thresholds to pulsatile and sinusoidal signals were recorded within the inferior
      colliculus (IC). Using previously established methods, spatial tuning curves
      (STCs; threshold vs. IC depth functions) were constructed, and their widths
      measured to infer spatial selectivity. The IC spatial representations were
      similar for pulsatile and sinusoidal stimulation when phase duration was taken
      into consideration. However, sinusoidal signals consistently elicited much lower
      thresholds than pulsatile signals, a difference not solely attributable to
      differences in charge/phase. The average STC width was significantly broader in
      the adult deafened/stimulated animals than in controls (adult
      deafened/unstimulated cats), suggesting that electrical stimulation can induce
      spatial expansion of the IC representation of the chronically stimulated cochlear
      sector. Further, results in these adult animals were not significantly different
      from results in neonatally deafened, early stimulated animals, suggesting that a
      similar degree of plasticity was induced within the auditory midbrains of mature
      animals.

PMID- 11950529
TI  - Axodendritic and dendrodendritic synapses within outer spiral bundles in a human.
AB  - Axodendritic and dendrodendritic synapses have been described at the level of the
      outer spiral bundle (OSB) (Nadol, J.B., Jr., 1983. Laryngoscope 93, 780-791;
      Bodian, D., 1978. Proc. Natl. Acad. Sci. USA 75, 4582-4586). The objectives of
      this study were to quantify these synaptic interactions and to describe their
      ultrastructural morphology in a young human subject. The temporal bone of an 8
      month old infant was processed for transmission electron microscopy and
      semiserial section reconstructions of the three OSBs were performed. The nerve
      fibers ((NFs)) forming the OSBs were found to segregate into two morphological
      groups: (1) vesicle-rich and neurofilament-poor (VR/NP); (2) vesicle-poor and
      neurofilament-rich (VP/NR). Synapses between VR/NP and VP/NR NFs and synapses
      between two VP/NR NFs were quantified. Presumed axodendritic synapses (i.e.
      between VR/NP and VP/NR NFs) were numerous and their numbers decreased from the
      first towards the third row. Presumed dendrodendritic synapses (i.e. between two
      VP/NR NFs) were also frequent but their numbers did not vary significantly among
      different rows. The presence of axodendritic synapses may provide the
      morphological basis for modulation of the function of the type II spiral ganglion
      cells (type II's) by the olivocochlear efferent system. Similarly, numerous
      presumed dendrodendritic synapses may provide a morphological substrate for
      interaction between dendrites of type II's.

PMID- 11950530
TI  - Smooth muscle in the annulus fibrosus of the tympanic membrane: physiological
      effects on sound transmission in the gerbil.
AB  - In a wide variety of mammals, the rim of the tympanic membrane (annulus fibrosus)
      has an array of contractile elements, either smooth muscle [Henson and Henson, J.
      Assoc. Res. Otolaryngol. 1 (2000) 25-32] or myofibroblasts [Kuijpers et al.,
      Hear. Res. 128 (1999) 80-88]. These elements are anchored peripherally to the
      bony tympanic ring and centrally to incoming fibers of the pars tensa. Their
      arrangement suggests that they are involved in the control of tympanic membrane
      tension. In this study, cochlear microphonic (CM) threshold changes were recorded
      in gerbils to study the physiological effects of these contractile elements. It
      was demonstrated that the application of substances known to make smooth muscle
      contract (vanadate and norepinephrine) caused concentration-dependent elevations
      in CM thresholds. Maximum changes of 8-9 dB occurred with the lowest frequency
      tested (2.16 kHz). The application of muscle-relaxing drugs reversed these
      effects. Controls showed that the threshold changes were not induced by effects
      on middle or inner ear structures. These results add to emerging evidence that
      the tympanic membrane has intrinsic control of tension and is potentially able to
      have some control over energy levels reaching the cochlea.

PMID- 11950532
TI  - Effects of conductive hearing loss on auditory nerve activity in gerbil.
AB  - The goal of this research was to define the effects of conductive hearing loss
      (CHL) produced by malleus removal (MR) on auditory nerve activity in the absence
      of acoustic stimulation. Subjects were gerbils in two age groups: 21 days (P21)
      and 42 days (P42). Ensemble background activity (EBA) of the auditory nerve was
      measured by spectral analysis of a signal recorded from the round window. The EBA
      measure was studied following MR in an acute setting in P42 animals, and in
      chronic experiments either 5 days (P21 and P42 animals) or 3 weeks (P21 animals)
      after MR. Findings were: (1) an EBA can be reliably measured in the gerbil, and
      this measure is highly stable over time; (2) the EBA is eliminated by application
      of tetrodotoxin, confirming the auditory nerve as the source of this measure; (3)
      MR results in a statistically significant decrease in the magnitude of the EBA in
      adult animals; and (4) the EBA measure is age-dependent. The EBA was
      significantly lower in P21 than in P42 animals, and response to MR varied as a
      function of age. We conclude that CHL decreases 'spontaneous' activity of the
      auditory nerve in young adult gerbils.

PMID- 11950531
TI  - Leupeptin protects cochlear and vestibular hair cells from gentamicin
      ototoxicity.
AB  - Calpains, a family of calcium-activated proteases that breakdown proteins,
      kinases, phosphatases and transcription factors, can promote cell death. Since
      leupeptin, a calpain inhibitor, protected against hair cell loss from acoustic
      overstimulation, we hypothesized that it might protect cochlear and vestibular
      hair cells against gentamicin (GM) ototoxicity. To test this hypothesis, mouse
      organotypic cultures from the cochlea, maculae of the utricle and the crista of
      the semicircular canal (P1-P3) were treated with different doses of GM (0.1-3 mM)
      alone or in the presence of leupeptin (0.1-3 mM). The percentage of outer hair
      cells (OHCs) and inner hair cells (IHCs) decreased with increasing doses of GM
      between 0.1 and 3 mM. The addition of 1 mM of leupeptin significantly reduced GM
      induced damage to IHCs and OHCs; this protective effect was dose-dependent. GM
      also significantly reduced hair cell density in the crista and utricle in a dose
      dependent manner between 0.1 and 3 mM. The addition of 1 mM of leupeptin
      significantly reduced hair cell loss in the crista and utricle for GM
      concentrations between 0.1 and 3 mM. These results suggest that one of the early
      steps in GM ototoxicity may involve calcium-activated proteases that lead to the
      demise of cochlear and vestibular hair cells.

PMID- 11950533
TI  - Partial recovery of cisplatin-induced hearing loss in the albino guinea pig in
      relation to cisplatin dose.
AB  - The objective of the present study was to further characterize cochlear recovery
      after cisplatin damage. We equipped albino guinea pigs with permanent round
      window electrodes. Cisplatin was injected i.p. on a daily basis at either 1.5 or
      2.0 mg/kg/day. Treatment was stopped when the criterion of > or =40 dB loss in
      the compound action potential iso-response level at 8 kHz had occurred. Either
      shortly (1-3 days) or long (4 weeks or more) after this stop, the endocochlear
      potential (EP) was measured and all animals were sacrificed for histology. At a
      cisplatin dose of 2.0 mg/kg/day, the time needed to reach the criterion hearing
      loss varied from 5 to 11 days. With 1.5 mg/kg/day this period lasted longer, the
      cumulative dose being the first-order predictor. The cochlear potentials
      gradually recovered in the first 2 weeks after treatment. At the lower
      frequencies, recovery was often complete. At the higher frequencies complete
      recovery was never seen. EP was depressed when measured just after treatment but
      had normal values long after. Basal outer hair cell (OHC) loss was found for both
      the short and the long post-treatment period. Thus, loss and recovery of cochlear
      potentials can for a large part be explained by loss and recovery of the EP.
      Recovery is limited by permanent OHC loss.

PMID- 11950534
TI  - Na+,K+-ATPase activity and ultrastructural localization in the tegmentum
      vasculosum in the cochlea of the duckling.
AB  - The tegmentum vasculosum of the avian cochlear duct mimics the stria vascularis
      of the mammalian cochlear duct in both location and structure, and previous
      studies indicate that it may be its functional counterpart with regard to
      endolymph synthesis. In the present study, we report on the enzymatic activity
      and ultrastructural localization of the Na+,K+-ATPase in the tegmentum vasculosum
      of the duckling. Na+,K+-ATPase activity was determined by measuring K+-dependent,
      ouabain-sensitive p-nitrophenyl phosphatase (p-NPPase) activity in homogenates of
      dissected regions of the cochlear duct. The ultrastructural localization of the
      Na+,K+-ATPase was identified using K+-dependent, ouabain-sensitive, p-NPPase
      cytochemistry. Specific enzyme activity was localized primarily in homogenates of
      the tegmentum vasculosum (2.27 micromol p-nitrophenyl phosphate/mg protein/min)
      when compared to homogenates of the entire cochlear duct (0.69 micromol p
      nitrophenyl phosphate/mg protein/min). Reaction product for p-NPPase was
      localized primarily along the basolateral plasma membrane folds of the dark
      cells. The cytochemical deposits appeared to be located exclusively on the
      cytoplasmic side of the plasma membrane. The light cells were devoid of reaction
      product. Biochemical and cytochemical localization of p-NPPase activity on the
      basolateral plasma membrane folds of the dark cells of the tegmentum vasculosum
      in conjunction with the ultrastructural morphology of these cells is compatible
      with a Na+,K+-ATPase-dependent ion transport function related to endolymph
      synthesis.

PMID- 11950535
TI  - Ultrastructure and blood supply of the tegmentum vasculosum in the cochlea of the
      duckling.
AB  - The tegmentum vasculosum of the duckling consists of a highly folded epithelium
      which extends over the dorsal and lateral walls of the cochlear duct, separating
      the scala media from the scala vestibuli. This epithelium consists of two
      distinct cell types, dark cells and light cells, and is well vascularized. The
      surface of the epithelium is formed by a mosaic of alternating dark and light
      cells. The goblet-shaped dark cells have an electron-dense, organelle-rich
      cytoplasm, and are expanded basally by extensive basolateral plasma membrane
      infoldings, within which are numerous mitochondria. Dark cells are isolated from
      each other and from the capillaries within the epithelium by intervening light
      cells. In contrast, columnar light cells exhibit an electron-lucent, organelle
      poor cytoplasm and may extend from the underlying capillaries to the
      endolymphatic surface. Light cells contain abundant, coated endocytic vesicles on
      their apical surfaces and are bound, apically, to other light cells or to dark
      cells by tight junctions and desmosomes. Laterally, light cells are linked to
      each other either by complex, fluid-filled membrane interdigitations or by
      extensive gap junctions. Plasma membrane interdigitations and obvious, fluid
      filled intercellular spaces characterize the lateral borders between light and
      dark cells. Vascular corrosion casting reveals the three-dimensional anatomy of
      the cochlear vasculature. A continuous arteriolar loop fed by anterior and
      posterior cochlear arterioles encircles the cochlear duct. The rich capillary
      beds of the tegmentum vasculosum are supplied by arching arterioles arising from
      this loop. These capillaries are the continuous type and are situated primarily
      within the core of the epithelium or along its border with the scala vestibuli.
      The structure and blood supply of the tegmentum vasculosum are characteristic of
      an epithelium involved in active transport.

PMID- 11950536
TI  - Age dependent changes in the medial nucleus of the trapezoid body in gerbils.
AB  - The results of a quantitative light microscopic analysis of serial glycine
      immunoreacted sections through the medial nucleus of the trapezoid body (MNTB) of
      young and old gerbils are presented. Spongiform lesions were prominent in the
      MNTB of gerbils that were 3 years and older, but were virtually absent in animals
      below 1 year of age. In old animals the prevalence and density of spongiform
      lesions were most pronounced in the caudal MNTB and decreased towards the rostral
      MNTB. Total MNTB volume and rostro-caudal extent were independent of age and the
      cross-sectional area of MNTB varied in an identical fashion along the MNTB in
      young and old gerbils. Mean MNTB soma size (cross-sectional area) varied with the
      age of the animal. In young gerbils soma size increased between 1 and 6 months of
      age reaching a maximum near 160 microm(2). In old gerbils mean soma size was
      significantly reduced to 130 microm(2). At all three rostro-caudal positions
      analyzed along MNTB, soma size varied systematically being largest in the ventro
      lateral and smallest in the dorso-medial part of MNTB. The reduction of soma size
      in old animals appeared uniform across MNTB.

PMID- 11950537
TI  - Early development and degeneration of vestibular hair cells in bronx waltzer
      mutant mice.
AB  - In bronx waltzer mouse mutants, inner hair cells die at an early stage in their
      development, from around 17.5 days of gestation onwards. In contrast, outer hair
      cells appear to develop normally. Vestibular hair cells also degenerate, but the
      earliest signs of vestibular abnormalities have not yet been described. We looked
      at prenatal and early postnatal stages of vestibular development by scanning
      electron microscopy in the mutants, and established that vestibular hair cells
      (types I and II) never reach beyond the middle stages of differentiation (at
      least up to P2) and instead show signs of degeneration. Thus, it appears that the
      bronx waltzer gene product is required for the continued survival and
      differentiation of inner and vestibular hair cells past a set point in their
      development.

PMID- 11950538
TI  - Functional effects of a monoclonal antibody on mechanoelectrical transduction in
      outer hair cells.
AB  - The functional effect of a monoclonal antibody, RA6.3, on mechanoelectrical
      transduction (MET) of outer hair cells (OHCs) isolated from the adult guinea-pig
      cochlea was investigated. This antibody was raised by an antiidiotypic approach
      against amiloride binding sites. RA6.3 irreversibly reduced the receptor current,
      independent of membrane potential. The time course of the functional block was
      independent of dilution (1:100, 50 and 10), beginning 1.2+/-0.5 min after the
      start of application and decreasing exponentially with a time constant of 0.29+/
      0.18 min to 53+/-8% of the control current. The residual current was reversibly
      blocked by amiloride (300 microM), mainly at negative membrane potentials. Block
      of control current by amiloride was competitively inhibited by simultaneous
      application of RA6.3. These results suggest that RA6.3 binds to or in close
      proximity to amiloride receptor sites associated with the MET channels.
      Irreversibility, incompleteness, independence of membrane potential and
      independence of antibody dilution of the functional block can all be explained by
      irreversible binding of one antibody molecule to a receptor site, yielding a non
      blocked state, followed by a relatively slow, reversible transition to a blocked
      state. It is proposed that the reversible transition might represent
      intramolecular binding of the second antibody combining site to the second
      receptor site.

PMID- 11950539
TI  - Increases in spontaneous neural activity in the hamster dorsal cochlear nucleus
      following cisplatin treatment: a possible basis for cisplatin-induced tinnitus.
AB  - Recent investigations in the hamster have implicated increased spontaneous
      activity (SA) in the dorsal cochlear nucleus (DCN) as a contributing factor in
      the etiology of tinnitus induced by intense sound exposure. It might therefore be
      expected that increased SA would also develop in the DCN of hamsters treated with
      cisplatin, another cause of tinnitus. We tested this hypothesis by measuring the
      effects of cisplatin on SA in the DCN. Adult hamsters were divided into three
      groups, each receiving five injections of cisplatin at one of the following
      doses: 3 mg/kg, 2.25 mg/kg, or 1.5 mg/kg. Each group had corresponding controls
      receiving injections of isotonic saline. The effects of cisplatin were studied
      electrophysiologically 1 month after treatment by recording multiunit SA on the
      surface of the DCN. Measurements of SA were obtained in three rows of 13-15
      locations spaced roughly 100 microm apart and spanning the length of the DCN
      along the tonotopic axis. Effects of cisplatin were evaluated by comparing plots
      of mean SA vs. tonotopic locus for cisplatin-treated groups with those of their
      corresponding untreated control groups. The results demonstrated a consistently
      higher level of SA in cisplatin-treated groups than in untreated controls.
      Whereas the highest rates of mean SA in control groups were between 10 and 15
      events/s, the highest mean spontaneous rates in cisplatin-treated groups were
      between 25 and 38 events/s. The cisplatin-induced hyperactivity was greatest in
      the medial half of the DCN corresponding to the high frequency portion of the
      tonotopic range. These results suggest that cisplatin treatment is an effective
      inducer of hyperactivity in the DCN. This hyperactivity may be an important
      neural correlate of cisplatin-induced tinnitus.

PMID- 11950540
TI  - Exponential processes in human auditory excitation and adaptation.
AB  - Peripheral auditory adaptation has been studied extensively in animal models, and
      multiple exponential components have been identified. This study explores the
      feasibility of estimating these component processes for human listeners with a
      peripheral model of adaptation. The processes were estimated from off-frequency
      masked detection data that probed temporal masking responses to a gated
      narrowband masker. The resulting response patterns reflected step-like onset and
      offset features with characteristically little evidence of confounding backward
      and forward masking. The model was implemented with linear combinations of
      exponential functions to represent the unadapted excitation response to gating
      the masker on and then off and the opposing effects of adaptation in each
      instance. The onset and offset of the temporal masking response were assumed to
      be approximately inverse operations and were modeled independently in this
      scheme. The unadapted excitation response at masker onset and the reversed
      excitation response at masker offset were each represented in the model by a
      single exponential function. The adaptation processes were modeled by three
      independent exponential functions, which were reversed at masker offset. Each
      adaptation component was subtractive and partially negated the unadapted
      excitation response to the dynamic masker. This scheme allowed for quantification
      of the response amplitude, action latency, and time constant for the unadapted
      excitation component and for each adaptation component. The results reveal that
      (1) the amplitudes of the unadapted excitation and reversed excitation components
      grow nonlinearly with masker level and mirror the 'compressive' input-output
      velocity response of the basilar membrane; (2) the time constants for the
      unadapted excitation and reversed excitation components are related inversely to
      masker intensity, which is compatible with neural synchrony increasing at masker
      onset (or offset) with increasing masker strength; (3) the composite strength of
      adaptation levels off at high masker levels; this 'saturation' response is
      consistent with a diminished contribution from peripheral neural adaptation
      processes at high sound levels; and (4) the response dynamics for two of the
      adaptation components correspond generally to those for the 'very rapid'/'rapid'
      processes and 'short-term' processes described in animal studies of peripheral
      neural adaptation. The action latency of a third adaptation component suggests
      the role of a second-order peripheral or central process. This modeling exercise
      (1) indicates that multiple adaptation processes, whatever their origins,
      contribute substantively to the form of the temporal masking response and (2)
      supports a sum-of-exponentials scheme for estimating properties of the component
      processes.

PMID- 11950541
TI  - Deficiency in plasma membrane calcium ATPase isoform 2 increases susceptibility
      to noise-induced hearing loss in mice.
AB  - Susceptibility to noise-induced hearing loss (NIHL) is poorly understood at the
      genetic level. Mice homozygous for a null mutation in the plasma membrane Ca2+
      ATPase isoform 2 (PMCA2) gene are deaf (Kozel et al., 1998). PMCA2 is expressed
      on outer hair cell stereocilia (Furuta et al., 1998). Fridberger et al. (1998)
      observed that the outer hair cell cytoplasmic Ca2+ concentration rises following
      acoustic overstimulation. We hypothesized that Pmca2+/- mice may be more
      susceptible to NIHL. Since the auditory brainstem response (ABR) thresholds of
      Pmca2+/- mice vary with the presence of a modifier locus (Noben-Trauth et al.,
      1997), Pmca2+/- mice were outcrossed to normal hearing CAST/Ei mice. The pre
      exposure ABR thresholds of the resulting Pmca2+/+ and Pmca2+/- siblings were
      indistinguishable. Groups of these mice were exposed to varying intensities of
      broadband noise, and ABR threshold shifts were calculated. Fifteen days following
      an 8 h, 113 dB noise exposure, the Pmca2+/- mice displayed significant (P < or =
      0.0007) permanent threshold shifts at 16 and 32 kHz that were 15 or 25 dB greater
      than those observed in Pmca2+/+ littermates. Pmca2 may be the first gene with a
      known mutated protein product that confers increased susceptibility to NIHL.

PMID- 11950542
TI  - First-admission rates of schizophrenia in Denmark, 1980-1997: have they been
      increasing?
AB  - Studies have revealed a decrease in the treated incidence of schizophrenia up to
      1990. The reasons remain open to question. The authors examined first-admission
      rates of schizophrenia during the 1990s in Denmark. The results showed a
      significant increase in first-admission rates of both sexes. Apparently, the
      shift of diagnostic classification system in 1994 from ICD-8 to ICD-10 did not
      explain the increase as a whole, nor did the changing number of psychiatric beds
      during the decades.

PMID- 11950543
TI  - Exposure to sunlight, vitamin D and schizophrenia.
AB  - The hypothesis that vitamin D deficiency in pregnancy or early infancy may
      contribute to the aetiology of schizophrenia was tested by examining the
      relationship between population exposure to sunlight, which promotes the
      synthesis of vitamin D in the summer months, and the monthly rate of
      schizophrenic births in two large data sets--22,000 schizophrenic patients born
      in England or Wales between 1921 and 1960, and 8000 born in Scotland between 1932
      and 1960. No convincing relationship could be found in either cohort.

PMID- 11950544
TI  - Long-term trends in sunshine duration and its association with schizophrenia
      birth rates and age at first registration--data from Australia and the
      Netherlands.
AB  - BACKGROUND: Based on the well-described excess of schizophrenia births in winter
      and spring, we hypothesised that individuals with schizophrenia (a) would be more
      likely to be born during periods of decreased perinatal sunshine, and (b) those
      born during periods of less sunshine would have an earlier age of first
      registration. METHODS: We undertook an ecological analysis of long-term trends in
      perinatal sunshine duration and schizophrenia birth rates based on two mental
      health registers (Queensland, Australia n=6630; The Netherlands n=24,474). For
      each of the 480 months between 1931 and 1970, the agreement between slopes of the
      trends in psychosis and long-term sunshine duration series were assessed. Age at
      first registration was assessed by quartiles of long-term trends in perinatal
      sunshine duration. Males and females were assessed separately. RESULTS: Both the
      Dutch and Australian data showed a statistically significant association between
      falling long-term trends in sunshine duration around the time of birth and rising
      schizophrenia birth rates for males only. In both the Dutch and Australian data
      there were significant associations between earlier age of first registration and
      reduced long-term trends in sunshine duration around the time of birth for both
      males and females. CONCLUSIONS: A measure of long-term trends in perinatal
      sunshine duration was associated with two epidemiological features of
      schizophrenia in two separate data sets. Exposures related to sunshine duration
      warrant further consideration in schizophrenia research.

PMID- 11950545
TI  - Season of birth in Japanese patients with schizophrenia.
AB  - A number of North American and European studies have observed a higher proportion
      of winter births in schizophrenia patients. Fewer studies have investigated this
      issue in Asian populations, and the findings are not as consistent as in the
      studies of Western populations. A statistically significant excess of winter
      births has not been observed in Japanese or Korean studies, while some of the
      studies found a decreased number of summer births among their patients. We
      further investigated the issue in Japanese patients with schizophrenia (n=2985).
      No significant excess of winter births was observed. Spearman correlation between
      schizophrenia births and ambient temperature was not significant. However, a
      decrease in the summer births was found, consistent with most of the previous
      Japanese studies. When analyzed by gender, a decrease in summer births was found
      in males, but not in females. In addition, a trend towards an increase in winter
      births was observed and Spearman correlation between low ambient temperature and
      schizophrenia births was significant in male subjects. More significant
      seasonality of birth in male patients than in female patients might be related to
      more susceptibility to pre- or perinatal disturbances in neurodevelopment in
      males than in females.

PMID- 11950546
TI  - Incidence of schizophrenia in Surinam.
AB  - More than one-third of the population of Surinam has migrated to The Netherlands
      in the 1970s and 1980s. If selective migration explains the increased incidence
      in these migrants, one expects to find a very low incidence of the disorder in
      Surinam. We examined the medical records of the sole psychiatric hospital in
      Surinam and found that the mean annual rate of first admissions for schizophrenia
      or schizophreniform disorder (DSM-III-R criteria) in 1992 and 1993 was 1.61 per
      10,000 (95% Confidence interval: 1.24-1.98 per 10,000), a normal figure. These
      findings constitute a challenge to the hypothesis that selection explains the
      increased incidence in the migrants. The possibility of an increased incidence of
      the disorder in Surinam (which might also explain the increased incidence among
      migrants) has not been ruled out by the results of this study.

PMID- 11950547
TI  - Duration of untreated psychosis and cognitive deterioration in first-episode
      schizophrenia.
AB  - Cognitive impairment is an important clinical feature in many individuals with
      schizophrenia. Factors associated with cognitive deficit are not well
      established. Duration of untreated psychosis (DUP) has recently gained interest
      as a prognostic factor in schizophrenia. This study reports on the association
      between DUP and cognitive function. Subjects comprised 42 individuals (30 males,
      12 females) who experienced a first-episode of DSM-III-R schizophrenia or
      schizophreniform disorder. Cognitive function was determined at clinical
      stabilization using the WAIS-R. An estimate of cognitive deterioration was based
      on the WAIS-R subtest profile. Longer DUP, male gender, higher premorbid IQ and
      younger age at admission independently predicted cognitive deterioration. Poorer
      performance on Digit Symbol and Comprehension subtests was associated with longer
      DUP. The findings suggest that untreated psychosis compromises some aspects of
      cognitive function. Studies investigating the association between DUP and outcome
      should control for potentially confounding variables. Early treatment of
      psychosis could help to reduce the prominent cognitive deficit in first-episode
      schizophrenia.

PMID- 11950548
TI  - One year outcome in first episode psychosis: influence of DUP and other
      predictors.
AB  - BACKGROUND: A number of studies have reported evidence of a relationship between
      longer duration of untreated psychosis (DUP) and poorer outcome at 1 year while
      others have failed to find such evidence. It is possible that several other
      predictors may confound this relationship and there may be different predictors
      for different dimensions of outcome. In the current study we examined
      relationship between DUP and several other predictors, and 1 year outcome on rate
      and level of remission as well as level of positive, negative, depressive and
      anxiety symptoms in a community cohort of first episode psychosis patients.
      METHOD: All potential cases of a first episode of non-affective psychosis were
      assessed and offered treatment in a comprehensive treatment program. Data were
      collected on all patients who completed 1 year of treatment on a number of
      predictor variables (DUP, length of the prodromal period, age of onset, gender,
      pre-morbid adjustment during childhood and adolescence, diagnosis) and outcome
      variables (level of remission, positive, negative, depression and anxiety
      symptoms based on ratings on SAPS, SANS, CDS and HAS, respectively). Data were
      analysed using an analysis of variance, bivariate correlations and hierarchical
      regression analysis. RESULTS: Of a total of 130 patients were offered treatment,
      106 completed 1 year of treatment and complete data were available on 88
      subjects, 80% of whom met criteria for schizophrenia spectrum psychosis. The rate
      and level of remission were significantly higher for patients with shorter DUP
      (<22 weeks). DUP was the only independent predictor of the level of remission as
      well as reality distortion at 1 year; for disorganization syndrome and negative
      symptoms it was the age of onset and level of premorbid adjustment in
      adolescence, respectively; while the level of anxiety was predicted by the length
      of the prodrome. Additional predictors increased the variance explained by each
      model. CONCLUSION: Our results confirmed the independent role of DUP in remission
      and positive symptom outcome at 1 year, thus providing support for the enthusiasm
      for early intervention. However, the model including DUP and premorbid adjustment
      in early adolescence explained a greater amount of variance in outcome on
      positive symptoms than DUP alone. On the other hand, outcome on negative
      symptoms, disorganization and anxiety are more likely to be influenced by longer
      term characteristics such as premorbid adjustment, earlier age of onset, gender
      and the length of the prodromal period, and therefore may not be as responsive to
      effects of early intervention.

PMID- 11950549
TI  - Precipitation and determination of the onset and course of schizophrenia by
      substance abuse--a retrospective and prospective study of 232 population-based
      first illness episodes.
AB  - Onset and lifetime prevalence of substance abuse were assessed retrospectively
      using the IRAOS interview in a population-based, controlled sample of 232 first
      episodes of schizophrenia (ABC sample). Subjects with schizophrenia were twice as
      likely as controls to have a lifetime history of substance abuse at the age of
      first admission (alcohol abuse: 23.7 versus 12.3%; drug abuse: 14.2 versus 7.0%).
      88% of the patients with drug abuse took cannabis. The sequence of substance
      abuse and schizophrenia was studied on the timing of abuse onset and illness
      onset, the latter as based on various definitions: first sign of the disorder,
      first psychotic symptom and first admission. 62% of the patients with drug abuse
      and 51% of those with alcohol abuse began the habit before illness onset (=first
      sign of the disorder). Abuse onset and illness onset occurred highly
      significantly within the same month (drug abuse in 34.6%, alcohol abuse in
      18.2%). Unexpectedly, no temporal correlation was found between abuse onset and
      the onset of the first psychotic episode. We concluded that a small proportion of
      schizophrenias might have been precipitated by substance--mainly cannabis--abuse.
      Long-term effects of early substance abuse were studied prospectively at six
      cross-sections over five years from first admission on in a subsample of 115
      first episodes of schizophrenia. Abusers showed significantly more positive
      symptoms and a decrease in affective flattening compared with controls. Five-year
      outcome as based on treatment compliance, utilization of rehabilitative measures
      and rate of employment was also poorer for patients with than without early
      substance abuse.

PMID- 11950550
TI  - Medication compliance and comorbid substance abuse in schizophrenia: impact on
      community survival 4 years after a relapse.
AB  - This prospective study examined the effect of medication compliance and substance
      abuse on 4 year outcome in 99 patients following a relapse of schizophrenia.
      Univariate survival analysis revealed longer community tenure in patients if they
      were over the age of 35 years, not admitted 2 years prior to the index episode,
      remained medication compliant and did not abuse substances during the follow-up
      interval. Comparisons between patients grouped according to medication compliance
      and current substance abuse indicated that those patients who regularly took
      their medication but also abused substances were readmitted to hospital sooner
      (median survival, 10 months) compared to compliant patients who did not use
      substances (37 months). For noncompliant patients, time to first readmission was
      shorter for patients with a dual diagnosis (5 months) compared to patients with a
      singular diagnosis of schizophrenia (10 months). Over the 4 year period,
      noncompliant patients with a dual diagnosis (n=28) accounted for 57% of all
      hospital readmissions for the cohort and averaged 1.5 admissions per patient
      year. These data indicate that much of the benefit that antipsychotic medication
      has on increasing community survival is reduced by substance abuse. This interval
      is further reduced in patients who are both substance abusers and noncompliant
      with medication resulting in a revolving door situation of frequent hospital
      admissions. Integrated treatment programs which address these issues are likely
      to reduce the need for hospital readmission in patients with a dual diagnosis.

PMID- 11950551
TI  - Mortality in chronic schizophrenia during decreasing number of psychiatric beds
      in Finland.
AB  - Mortality, especially mortality due to suicides, is higher among patients
      suffering from schizophrenia than among the general population. Little is known
      about the factors predicting the mortality of schizophrenia patients. It has also
      been suggested that mortality among psychiatric patients increases as the number
      of beds in mental hospitals decreases. These questions were studied in 4338
      schizophrenia patients discharged in 1982, 1986, 1990 and 1994 from mental
      hospitals in Finland. During this period, the number of beds in mental hospitals
      in Finland decreased from 3.8 to 1.3 per 1000 inhabitants. During the three-year
      follow-up, 226 patients or 5.2% died. There were no statistically significant
      differences in mortality between the cohorts. The total mortality was higher in
      males than in females. Age, physical illness and number of hospital days
      predicted increased mortality due to natural causes. Mortality due to unnatural
      causes (suicides and accidents) was predicted by number of prescribed
      psychosedatives, number of hospitalisations and short duration of illness.
      Mortality due to unnatural causes was higher in the first year after index
      discharge from hospital. The reduction in number of beds in mental hospitals does
      not seem to be associated with increased mortality in chronic schizophrenia. The
      high mortality of schizophrenia patients indicates the need for careful medical
      examinations and treatment of physical illnesses, as well as counselling for a
      healthy lifestyle. Need for psychosedative medication at discharge from hospital
      and multiple previous hospitalisations may indicate an increased suicide risk and
      thus requires special attention. In outpatient treatment, it is important to
      remember that the risk of unnatural death increases during the first years after
      discharge from hospital.

PMID- 11950552
TI  - Age-at-first-registration in schizophrenia: a comparison of mental health
      registers from Australia and Brazil.

PMID- 11950553
TI  - Increased serum interleukin-8 and interleukin-10 in schizophrenic patients
      resistant to treatment with neuroleptics and the stimulatory effects of clozapine
      on serum leukemia inhibitory factor receptor.
AB  - There is now evidence that schizophrenia may be accompanied by an activation of
      the monocytic and T-helper-2 (Th-2) arms of cell-mediated immunity (CMI) and by
      various alterations in the Th-1 arm of CMI. There is also evidence that repeated
      administration of typical and atypical antipsychotics may result in negative
      immunomodulatory effects. This study was carried out to examine (1) the serum
      concentrations of interleukin-8 (IL-8), IL-10, the soluble CD8 (sCD8) and the
      leukemia inhibitory factor receptor (LIF-R) in nonresponders to treatment with
      typical neuroleptics as compared with normal volunteers and responders to
      treatment; and (2) the effects of atypical antipsychotics on the above immune
      variables. The latter were determined in 17 nonresponders to treatment with
      neuroleptics and in seven normal volunteers and 14 schizophrenic patients who had
      a good response to treatment with antipsychotic agents. The nonresponders had
      repeated measurements of the immune variables before, and 2 and 4 months after
      treatment with clozapine or risperidone. Serum IL-8 and IL-10 were significantly
      higher in schizophrenic patients than in normal controls. The serum
      concentrations of the sCD8 were significantly increased 2 months, but not 4
      months, after starting treatment with atypical antipsychotics. Serum LIF-R
      concentrations were significantly increased 2 and 4 months after starting
      treatment with atypical antipsychotics. It is concluded that: (1) schizophrenia
      is characterized by an activation of both pro-inflammatory and anti-inflammatory
      aspects of cell-mediated immunity; (2) prolonged treatment with atypical
      antipsychotics may increase the anti-inflammatory capacity of the serum in
      schizophrenic patients by increasing serum LIF-R concentrations; and (3) short
      term treatment with clozapine may induce signs of immune activation which
      disappear upon prolonged treatment.

PMID- 11950557
TI  - Functional materials for microscale genomic and proteomic analyses.
AB  - The design of functional materials for genomic and proteomic analyses in
      microscale systems has begun to mature, from materials designed for capillary
      based electrophoresis systems to those tailored for microfluidic-based or 'chip
      based' platforms. In particular, recent research has focused on evaluating
      different polymer chemistries for microchannel surface passivation and improved
      DNA separation matrix performance. Additionally, novel bioconjugate materials
      designed specifically for electrophoretic separations in microscale channels are
      facilitating new separation modalities.

PMID- 11950559
TI  - Directed evolution of enzymes and pathways for industrial biocatalysis.
AB  - Directed evolution has become a powerful tool for developing enzyme and whole
      cell based biocatalysts. Significant recent advances include the creation of
      novel enzyme functions and the development of several new efficient directed
      evolution methods. The combination of directed evolution and rational design
      promises to accelerate the development of biocatalysts for applications in the
      pharmaceutical, chemical and food industries.

PMID- 11950558
TI  - Process chromatography: current constraints and future options for the adsorptive
      recovery of bioproducts.
AB  - A contemporary review of adsorption chromatography must embrace aspects of fixed
      bed, batch suspension and fluidised-bed contacting of complex feedstocks with
      adsorbents chemically derivatised with ligands with binding specificities for
      target bioproducts. Advances in the design of adsorbents, ligands and contactors
      have facilitated opportunities for integrated processing of unclarified
      feedstocks to benefit purity and yield of macromolecular products. In the face of
      competition from apparently simpler, yet productive, technologies (e.g.
      precipitation, crystallisation and aqueous solvent extraction), further advances
      in chromatographic purification of macromolecules and nanoparticulates demand
      close collaboration between inventors and/or manufacturers of new products and
      the suppliers of chromatographic hardware and consumables.

PMID- 11950560
TI  - Enzyme technology and bioprocess engineering.
AB  - The impact of directed evolution and site-specific mutagenesis on the industrial
      utility of enzymatic catalysis through the modification of enzyme structure and
      function is clearly an important area of research in bioprocess engineering. High
      throughput screening for novel or improved enzyme activities, both by more
      efficiently exploring nature's diversity and by creating new diversity in the
      test tube, allows new bioprocesses to be developed. Similarly, innovations in
      enzyme technology that address novel ways to apply enzymes in bioprocesses also
      have an impact on bioprocess engineering. Several recent developments have been
      made in this latter aspect of bioprocess engineering.

PMID- 11950561
TI  - Recombinant protein expression for therapeutic applications.
AB  - In recent years, the number of recombinant proteins used for therapeutic
      applications has increased dramatically. Many of these applications involve
      complex glycoproteins and antibodies with relatively high production needs. These
      demands have driven the development of a variety of improvements in protein
      expression technology, particularly involving mammalian and microbial culture
      systems.

PMID- 11950562
TI  - Bioprocess monitoring.
AB  - Electrochemical sensors for pH and dissolved oxygen remain the most commonly used
      in bioprocess monitoring, but continued research has resulted in improved optical
      sensors. Optical sensors for dissolved oxygen and dissolved carbon dioxide are
      now commercially available. Advances in optics and electronics are further
      driving down the costs of these sensors. In the near future, bioprocess
      optimization will change paradigms as massively parallel, fully instrumented
      bioreactors become available and high-throughput bioprocessing becomes a reality.

PMID- 11950563
TI  - Non-viral gene delivery systems.
AB  - Non-viral gene delivery systems have the potential to create viable
      pharmaceuticals from nucleic acids. These DNA delivery systems contain lipids
      and/or cationic polymers. In order for these systems to be developed into
      commercial products, several barriers must be overcome. These include obstacles
      in manufacturing, formulation and stability. In vivo, problems of extracellular
      non-specific interactions and intracellular trafficking to the nucleus are also
      encountered. Recent progress has been made in overcoming these issues.

PMID- 11950564
TI  - Multigenes and multipurpose genes.

PMID- 11950566
TI  - Improving iron, zinc and vitamin A nutrition through plant biotechnology.
AB  - Recent understanding of plant metabolism has made it possible to increase the
      iron, zinc and beta-carotene (provitamin A) content in staple foods by both
      conventional plant breeding and genetic engineering. Improving the micronutrient
      composition of plant foods may become a sustainable strategy to combat
      deficiencies in human populations, replacing or complementing other strategies
      such as food fortification or nutrient supplementation.

PMID- 11950565
TI  - Multigene engineering: dawn of an exciting new era in biotechnology.
AB  - Development of a rice variety enriched in provitamin A, the accumulation of
      polyhydroxybutyrate polyester in Arabidopsis nuclear transgenic plants (with
      enzymes targeted to chloroplasts in both), and the expression of bacterial
      operons via the chloroplast genome are recent landmark achievements in multigene
      engineering. Hyper-expression of transgenes has resulted in the formation of
      insecticidal protein crystals or inclusion bodies of pharmaceutical proteins in
      transgenic chloroplasts, achieving the highest level of transgene expression ever
      reported in transgenic plants. These achievements illustrate the potential of
      multigene engineering to realize benefits of the post-genomic revolution.

PMID- 11950567
TI  - Engineering salt tolerance in plants.
AB  - Recent progress has been made in the identification and characterization of the
      mechanisms that allow plants to tolerate high salt concentrations. The
      understanding of metabolic fluxes and the main constraints for the production of
      compatible solutes (i.e. feedback inhibition and the limitation of substrate
      supply) open up the possibility of genetically engineering entire pathways that
      could lead to the production of osmoprotectants. This, together with the
      identification of the different sodium transporters (in particular vacuolar and
      plasma membrane Na(+)/H(+) antiporters) that could provide the needed ion
      homeostasis during salt stress, opens the possibility of engineering crop plants
      with improved salt tolerance.

PMID- 11950569
TI  - Can we discover novel pathways using metabolomic analysis?
AB  - Metabolomic analysis aims at the identification and quantitation of all
      metabolites in a given biological sample. Current data acquisition and network
      analysis strategies are classified on the basis of pathway elucidation and
      characteristics of theoretical networks. The development of metabolomic methods
      and tools is progressing rapidly, but an understanding of the resulting data is
      limited owing to a fundamental lack of biochemical and physiological knowledge
      about network organization in plants.

PMID- 11950568
TI  - Growing up fast: manipulating the generation time of trees.
AB  - Domestication and genetic improvement of trees is far behind that of herbaceous
      plants owing to their long generation times, which result from the existence of a
      long juvenile phase of reproductive incompetence. During recent years,
      significant progress has been made towards understanding the molecular basis of
      flowering transition in model herbaceous species. Some of the genes identified
      have been shown to efficiently accelerate reproductive development when
      ectopically expressed in transgenic plants, including trees. These results
      provide new clues as to the molecular basis of reproductive competence in trees
      and suggest ways to accelerate their genetic improvement.

PMID- 11950570
TI  - Plantibodies: applications, advantages and bottlenecks.
AB  - Various strategies have been developed to exploit plants as bioreactors for the
      production of pharmaceutical antibodies, to engineer antibody-mediated pathogen
      resistance or to alter the plant phenotype by immunomodulation. Recent research
      developments focus on the fine-tuning of expression systems and the detailed
      characterisation of recombinant products, including the implications of plant
      specific glycosylation. Meanwhile, the first of these plant-derived antibody
      products has successfully completed early phase clinical trials.

PMID- 11950571
TI  - RNA-mediated virus resistance.
AB  - Post-transcriptional gene silencing is an RNA degradation mechanism that can be
      induced by viruses. Recent evidence indicates that silencing may also be involved
      in virus synergism, tissue limitation of virus spread, non-host resistance, virus
      transmission through seeds and in more general mechanisms of defense such as that
      mediated by salicylic acid. The analysis of Arabidopsis mutants, and of viruses
      carrying silencing suppressors, has led to a greater understanding of post
      transcriptional gene silencing pathways. Much still remains to be discovered,
      however, not least to allow the successful exploitation of gene silencing in
      conferring pathogen resistance to transgenic plants.

PMID- 11950572
TI  - Marker-free transformation: increasing transformation frequency by the use of
      regeneration-promoting genes.
AB  - The generation of transgenic plants free of antibiotic resistance markers is a
      major challenge to plant biologists and plant breeders. Currently, there are two
      main strategies to achieve this goal: one approach is to excise or segregate
      marker genes from the host genome after regeneration of transgenic plants, and
      the second is based on so-called 'marker-free' transformation. Marker-free
      transformation has been successfully demonstrated by the use of several plant and
      non-plant genes that are capable of promoting explant regeneration. This approach
      appears not only to be effective for the generation of marker-free transgenic
      plants, but also has great potential to improve the transformation frequency of
      recalcitrant species.

PMID- 11950573
TI  - Engineering secondary metabolite production in plants.
AB  - Recent achievements have been made in the metabolic engineering of plant
      secondary metabolism. Various pathways have been altered using genes encoding
      biosynthetic enzymes or genes encoding regulatory proteins. In addition,
      antisense genes have been used to block competitive pathways, thereby increasing
      the flux towards the desired secondary metabolites.

PMID- 11950574
TI  - Realignment osteotomy for knee deformity in childhood.

PMID- 11950575
TI  - Current Australian trends in rehabilitation following anterior cruciate ligament
      reconstruction.
AB  - This study documented the current approaches to rehabilitation following anterior
      cruciate ligament (ACL) reconstruction by Australian orthopaedic surgeons. A two
      page questionnaire was mailed to the 40 members of the Australian Knee Society to
      obtain information regarding (1) pre-operative requirements; (2) immediate post
      operative requirements; and (3) the timing of the introduction of rehabilitation
      phases and return to sport following ACL reconstruction. The response rate of
      practising surgeons was 95%. Twenty-two surgeons (61%) regularly performed both
      hamstring tendon (HS) and patellar tendon (PT) ACL reconstruction. Eighty-three
      percent had a standard rehabilitation protocol, and of these, 23% had separate
      protocols for the two graft types. There were no significant differences between
      the responses for the two graft types for any question. Approximately three
      quarters of surgeons (HS: 75%, PT: 78%) had specific pre-operative requirements.
      Most surgeons (HS: 96%, PT: 93%) had specific post-operative requirements.
      Physiotherapy was routinely used by 96% and 93% of surgeons for HS and PT grafts,
      respectively, commencing at a mean of 2 weeks post-operatively for HS grafts and
      a mean of 1.5 weeks for PT grafts. Progression through rehabilitation and the
      timing of return to various levels of sporting activity was similar for both
      graft types. Few surgeons used strength testing (HS: 25%, PT: 23%) or knee
      arthrometry (HS: 22%, PT: 17%) prior to return to sport and the use of a brace
      was rarely recommended for return to sport (HS: 7%, PT: 3%). The results of this
      survey indicate little variation in the post-operative management of HS and PT
      ACL reconstruction among members of the Australian Knee Society. Future research
      should, however, be directed towards the rate of progression through
      rehabilitation, as this was shown to be more conservative than other recent
      reports.

PMID- 11950576
TI  - High tibial osteotomy with anterior advancement of distal fragment for medial and
      patellofemoral compartmental osteoarthritis of the knee.
AB  - High tibial osteotomy was performed in 73 knees of 50 patients with medial and
      patellofemoral compartmental osteoarthritis of the knee, which was combined with
      anterior advancement of the distal fragment. At the operation, parapatellar
      release of the retinaculum and subperiosteal elevation of contracted medial soft
      tissue were also adjoined. The average age of the patients at the time of surgery
      was 64 years. The follow-up period was an average of 58 months. On overall
      clinical results assessed with the Knee Society score, the average total knee
      score was improved from preoperative 50 points to postoperative 94, and the
      preoperative average functional score of 47 points increased to 92
      postoperatively. At follow-up, pain from a grinding patella was not found in 68
      of 73 knees and pain from grinding and deviating of the patella was relieved in
      more than 96% of all cases. The mean femorotibial angle was reduced from
      preoperative 185 degrees to postoperative 167 degrees. On skyline view, the width
      of the lateral facet joint space was widely opened postoperatively, particularly
      on the flexion angle of 90 degrees. This operative procedure successfully
      relieved patellofemoral symptoms of the patients with medial and patellofemoral
      compartmental osteoarthritis of the knee.

PMID- 11950577
TI  - Ten to fourteen year survival and functional analysis of the AGC total knee
      replacement system.
AB  - A study of 562 Anatomic Graduated Component (AGC) total knee arthroplasties that
      were performed in 402 patients between November 1986 and September 1990 is
      reported. All patients had implantation with a cemented posterior cruciate
      retaining design, with resurfacing of the patella using all polyethylene patella
      components. Mean age at surgery was 71 years (range 41-92 years). Patients were
      followed for a minimum of 10 years (range 10-14 years). Nine knees were lost to
      follow-up (1.4%). The mean Knee Society Score for pain and function were analyzed
      by Charnley categories: Category A -- 97 (pain) and 89 (function); Category B --
      91 (pain) and 84 (function); and Category C -- 89 (pain) and 62 (function). The
      survival analysis at 14 years was 97% with revision for any reason as the
      endpoint and the authors continue to utilize this implant system.

PMID- 11950578
TI  - Correlation of MR imaging findings and open exploration of medial patellofemoral
      ligament injuries in acute patellar dislocations.
AB  - The purpose of this investigation was to correlate magnetic resonance (MR) images
      of medial patellofemoral ligament (MPFL) injuries with gross macroscopic
      findings. Twenty-seven knees with MPFL injury following an initial patellar
      dislocation were examined using axial proton-density and T2-weighted fast spin
      echo MR imaging. MR findings were subsequently correlated with open exploration.
      MPFL injury was observed in 26 (96%) of the 27 knees. From the MR images,
      discontinuity, irregularity and/or high-signal intensity changes anterior to the
      femoral attachment were seen in 13 (82%) of the 16 knees with substantial-tear
      type injuries of the MPFL. In 8 (80%) of the 10 knees with avulsion-tear type
      injuries, detachment of the MPFL from the femoral attachment, accompanied with or
      without high-signal intensity changes, was confirmed. MPFL injury types could be
      accurately diagnosed on 21 (81%) out of 26 knees using MR imaging. MR imaging was
      an acceptable method in diagnosing MPFL injury types.

PMID- 11950579
TI  - Use of the blood transfusion service in total knee replacement arthroplasty. The
      cost implications.
AB  - In view of the rising costs of blood transfusion and reports of inappropriate
      transfusions an audit of the local practice was organised. The aim was to
      investigate whether blood transfusion in primary unilateral Total Knee
      replacement Arthroplasty (TKA) operations was being used inappropriately locally,
      the resultant cost implications and suggest ways of reducing these. A 1-year
      retrospective survey of blood transfusion practice was conducted for all
      consecutive elective, primary, unilateral TKA operations at a District-General
      Hospital. 169 operations were performed and 58 (34%) patients were transfused. A
      retrospective Haemoglobin concentration (Hb) analysis was performed for all the
      transfused patients to identify the number of transfusions that satisfied the
      suggested transfusion criteria of a threshold Hb of 8 g/dl and when indicated, a
      minimum transfusion of 2 units. Complete transfusion data was available on 49/58
      (84%) patients transfused. When applying the above criteria to this sample, the
      potential annual saving for the department was estimated at approximately 8000
      pounds Sterling; only 9 of these patients were deemed to be appropriately
      transfused.

PMID- 11950580
TI  - Virtual arthroscopy -- a personal view.

PMID- 11950581
TI  - Patellar instability following total knee replacement -- the dangers of constant
      design evolution.
AB  - Patellar instability following total knee replacement although infrequent can
      cause disabling symptoms. We report a case of symptomatic patellar instability
      caused by insertion of left femoral component into a right knee. We highlight
      that all members of the surgical and theatre team need to be familiar both with
      the implant equipment and of any recent design modifications, particularly if
      they have been used to using one system for a long time, in order to prevent
      surgical errors. In addition this possibility should be born in mind by surgeons
      looking for causes of post-operative patellar instability.

PMID- 11950582
TI  - Frozen autografts: an alternative to graft disposal.
AB  - The use of fresh frozen tendon allografts is a well-documented surgical
      technique. We present a case where a harvested semitendinosus autograft was
      preserved by deep-freezing, having abandoned the initial procedure due to
      infection. After treatment of the infection the graft was subsequently used to
      reconstruct the postero-lateral corner complex with no deleterious effect at 1
      year.

PMID- 11950583
TI  - Fracture of the tibial tubercle following anterior cruciate ligament
      reconstruction.
AB  - A case is presented of a traumatic avulsion fracture of part of the tibial
      tubercle after harvesting of the central third of the patellar tendon, with bone
      blocks, for anterior cruciate ligament (ACL) reconstruction. The literature is
      reviewed. This injury has not been reported previously.

PMID- 11950584
TI  - Glomus tumour, a rare cause of knee pain: a case report.

PMID- 11950585
TI  - Osteochondromatosis with high concentration of procollagen II C peptide in joint
      fluid.
AB  - Procollagen II C peptide is used as a joint fluid marker of collagen synthesis by
      chondrocytes in patients with osteoarthritis. Since osteochondromatosis activates
      ectopic chondrogenesis in the synovial membrane, procollagen II C peptide is
      expected to be a good marker of the disease. Procollagen II C peptide can be used
      to evaluate the condition of the disease metabolically by simply aspirating the
      joint fluid. We have experienced a case of osteochondromatosis (Miligram's stage
      2) with a high concentration of procollagen II C peptide. This case suggests that
      the concentration of procollagen II C peptide is a good marker of chondrogenesis
      by osteochondromatosis.

PMID- 11950586
TI  - The 14th annual symposium of the International Society for Technology in
      Arthroplasty.

PMID- 11950587
TI  - p21-activated kinases: three more join the Pak.
AB  - The p21-activated kinases (Paks) are serine/threonine protein kinases that bind
      to and, in some cases, are stimulated by activated forms of the small GTPases,
      Cdc42 and Rac. With the recent discovery of several novel isoforms, Paks are now
      categorized into two subgroups based on architectural similarities. The Group I
      Paks (Pak1, Pak2, Pak3) have been studied in greater detail and shown to be
      involved in the regulation of cellular processes such as gene transcription, cell
      morphology, motility, and apoptosis. Here we summarize recent findings that shed
      light on the newly recognized Group II Paks (Pak4, Pak5, Pak6) and review both
      similarities and differences between kinases of the two Pak subgroups.

PMID- 11950588
TI  - The hyaluronan receptor, CD44.
AB  - CD44 is a widely expressed cell surface hyaluronan receptor which plays a key
      role in mediating cell migration. A number of recent papers demonstrating an
      interplay between CD44 and matrix metalloproteinases (MMPs) have shed important
      insights into the molecular mechanisms underlying these events. This has
      important implication for understanding how mis-regulation of CD44 can contribute
      to disease pathologies.

PMID- 11950589
TI  - Calpain.
AB  - The calcium-dependent thiol proteases, calpains, are widely expressed with
      ubiquitous and tissue specific isoforms. Calpains have been implicated in basic
      cellular processes including cell proliferation, apoptosis and differentiation.
      The focus of the current review is to summarize recent findings implicating
      calpains in cytoskeletal rearrangements and cell migration. Calpain cleaves many
      cytosolic proteins and therefore to be effective and limited in its scope,
      calpain activity has to be tightly regulated both temporally and spatially. Some
      mechanisms of regulation include calcium, growth factor-mediated phosphorylation
      and membrane targeting. Calpain inhibition reduces migration rates and inhibits
      cell invasiveness. Two putative mechanisms of calpain action during migration
      include its role as a signaling intermediate, acting upstream of Rho, and its
      effects on focal adhesion structure and disassembly. Therefore, calpains and
      downstream signaling molecules may be future targets for therapeutic
      interventions to treat cancer or chronic inflammation.

PMID- 11950590
TI  - Structures in focus--filopodia.
AB  - Filopodia are thin cell surface extensions filled with tight parallel bundles of
      actin filaments. They are highly dynamic structures which rapidly extend and
      retract as well as sweep up and down and from side to side, and can be found at
      the leading edge of many types of motile cells such as fibroblasts and
      keratinocytes, as well as the growth cone tips of migrating axons. Cells appear
      to use filopodia to explore the extracellular matrix (ECM) and surfaces of other
      cells, identifying appropriate targets for adhesion or in the case of a migrating
      growth cone, for sensing guidance cues that enable the axon to navigate to it's
      appropriate target. As well as this sensory role, filopodia have also recently
      been shown to play an important mechanical role in epithelial adhesion, and are
      likely to be key players in developmental processes that require migrating
      epithelial sheets to zipper and fuse to one another. Their dynamic properties as
      well as their tendency to be damaged or lost after fixation mean they are best
      analysed using live imaging techniques. As this field improves, the number of
      tissues in which filopodia are seen to be playing key roles is fast increasing.

PMID- 11950591
TI  - The role of Rho GTPases and associated kinases in regulating neurite outgrowth.
AB  - Neurones are highly specialised cells that can extend over great distances,
      enabling the complex networking of the nervous system. We are beginning to
      understand in detail the molecular mechanisms that control the shape of neurones
      during development. One family of proteins that are clearly essential are the Rho
      GTPases which have a pivotal role in regulating the actin cytoskeleton in all
      cell types. The Rho GTPases are responsible for the activation and downregulation
      of many downstream kinases. This review discusses individual kinases that are
      regulated by three members of the Rho GTPases, Rac, Rho and Cdc42 and their
      function during neurite outgrowth and remodelling.

PMID- 11950592
TI  - Regulation of substrate adhesion dynamics during cell motility.
AB  - The movement of a metazoan cell entails the regulated creation and turnover of
      adhesions with the surface on which it moves. Adhesion sites form as a result of
      signaling between the extracellular matrix on the outside and the actin
      cytoskeleton on the inside, and they are associated with specific assembles of
      actin filaments. Two broad categories of adhesion sites can be distinguished: (1)
      "focal complexes" associated with lamellipodia and filopodia that support
      protrusion and traction at the cell front; and (2) "focal adhesions" at the
      termini of stress fibre bundles that serve in longer term anchorage. Focal
      complexes are signaled via Rac1 or Cdc42 and can either turnover on a minute
      scale or differentiate, via intervention of the RhoA pathway, into longer-lived
      focal adhesions. All classes of adhesion sites depend on the stress in the actin
      cytoskeleton for their formation and maintenance. Different cell types use
      different adhesion strategies to move, in terms of the relative engagement of
      filopodia and lamellipodia in focal complex formation and protrusion and the
      extent of focal adhesion formation. These differences can be attributed to
      variations in the relative activities of Rho family members. However, the Rho
      GTPases alone are unable to signal asymmetry in the actin cytoskeleton, necessary
      for polarisation and movement. Polarisation requires the collaboration of the
      microtubule cytoskeleton. Changes in the polymerisation state of microtubules
      influences the activities of both Rac1 and RhoA and microtubules interact
      directly with adhesion foci and promote their turnover. Possible mechanisms of
      cross-talk between the microtubule and actin cytoskeletons in determining
      polarity are discussed.

PMID- 11950593
TI  - Motility is rate-limiting for invasion of bladder carcinoma cell lines.
AB  - Induced migration of tumor cells is generally considered to be one critical step
      in cancer progression to the invasive and metastatic stage. The implicit caveat
      of studies that show this is that other, unknown, signaling pathways and
      biophysical events are actually the operative rate-limiting steps, and not
      motility per se. Thus, to examine the hypothesis that motility is a single, but
      overall rate-limiting function required for invasion, disparate motility
      processes need be blocked with concordant effects on tumor invasion. Recently, we
      and others have described two signaling pathways that are critical to growth
      factor-induced motility but not mitogenesis. The key molecular switches are
      phospholipase C-gamma (PLCgamma) and calpain for cytoskeletal reorganization and
      rear detachment, respectively. We examined this hypothesis in a highly invasive
      tumor, bladder carcinoma. Three different human tumor cell lines, 253J-B-V, UMUC
      and T-24, were tested for invasiveness in vitro by transmigration of a Matrigel
      barrier. Inhibiting PLCgamma with the pharmacologic agent U73122 or the molecular
      dominant-negative PLCz construct reduced both invasiveness and motility. The same
      was noted when calpain was blocked using calpain inhibitor I (ALLN). These
      results demonstrate that one interventional target for limiting invasion is not
      necessarily an individual motility pathway but rather cell migration per se.

PMID- 11950594
TI  - Distribution of gelsolin and phosphoinositol 4,5-bisphosphate in lamellipodia
      during EGF-induced motility.
AB  - During induced cell motility the actin cytoskeleton at the leading edge must
      undergo constant reorganization. Recently, phosphoinositides have been shown to
      be central to cytoskeleton-membrane linkages and actin organization and turnover.
      Epidermal growth factor (EGF) receptor (EGFR)-mediated cell motility requires
      phospholipase C-gamma (PLCgamma), hydrolysis of phosphoinsotide 4,5-bisphosphate
      (PIP(2)) and subsequent release of gelsolin. We hypothesized this led to the
      mobilization of PIP(2)-binding proteins which modify the actin cytoskeleton and
      thus sought to determine whether the leading edge was a site of active PIP(2)
      hydrolysis and gelsolin redistribution to cytoskeleton. Herein, we report that
      during EGF-induced motility, the leading edge's submembranous region constitutes
      a distinct subcellular locale. The relevant phosphoinositide composition of this
      space was determined by probing with an antibody to PIP(2) and a green
      fluorescence protein (GFP)-tagged pleckstrin homology (PH) domain of PLCdelta
      (GFP-PH) that recognizes both PIP(2) and inositol 1,4,5-trisphosphate (IP(3)).
      PIP(2) was absent from leading lamellipodia despite an increase in IP(3)
      generation, suggesting an increase in PIP(2) hydrolysis at the leading edge.
      Visualized with immunofluorescence, gelsolin preferentially concentrated near the
      leading edge in a punctate fashion. Examining the Triton X-insoluble actin
      cytoskeleton fractions, we observe a PLCgamma-dependent increase of gelsolin
      incorporation upon EGF stimulation. At a molecular level, field emission scanning
      electron microscopy (FE-SEM) shows that gelsolin incorporates preferentially into
      the submembranous actin arcs at the leading edge of the lamellipodia. Together
      these data suggest a model of PIP(2) hydrolysis at the leading edge causing a
      localized release of PIP(2)-binding proteins-particularly gelsolin-that drives
      cytoskeletal rearrangement and protrusion.

PMID- 11950596
TI  - Restoration of podosomes and chemotaxis in Wiskott-Aldrich syndrome macrophages
      following induced expression of WASp.
AB  - We used a direct-viewing (Dunn) chemotaxis chamber to analyse the chemotactic
      responses of human normal and Wiskott-Aldrich syndrome (WAS) macrophages to the
      cytokine colony stimulating factor-1 (CSF-1). In five patients with classic WAS,
      where specialised adhesion complexes called podosomes are absent, chemotaxis of
      macrophages was abolished. The deficient chemotactic responses of WAS macrophages
      following cytokine stimulation could be correlated with abnormalities in cell
      polarisation and actin organisation. In a series of cell microinjection studies
      we found that normal chemotactic responses were restored in WASp macrophages
      transfected with a full-length human WAS construct. Expression of exogenous WAS
      protein (WASp) in these cells also restored normal polarised cell morphology and
      the ability to form podosomes.

PMID- 11950595
TI  - Nck-2 interacts with focal adhesion kinase and modulates cell motility.
AB  - Nck-2 is a ubiquitously expressed adaptor protein comprising primarily three N
      terminal SH3 domains and one C-terminal SH2 domain. We report here that Nck-2
      interacts with focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase
      critically involved in the cellular control of motility. Using a mutational
      strategy, we have found that the formation of the Nck-2-FAK complex is mediated
      by interactions involving multiple SH2 and SH3 domains of Nck-2. The Nck-2 SH2
      domain-mediated interaction with FAK is dependent on phosphorylation of Tyr397, a
      site that is involved in the regulation of cell motility. A fraction of Nck-2 co
      localizes with FAK at cell periphery in spreading cells. Furthermore,
      overexpression of Nck-2 modestly decreased cell motility, whereas overexpression
      of a mutant form of Nck-2 containing the SH2 domain but lacking the SH3 domains
      significantly promoted cell motility. These results identify a novel interaction
      between Nck-2 and FAK and suggest a role of Nck-2 in the modulation of cell
      motility.

PMID- 11950597
TI  - Alignment of myoblasts on ultrafine gratings inhibits fusion in vitro.
AB  - During development, skeletal muscle precursor cells fuse to form multi-nucleated
      myotubes. However, it is unclear how this fusion is regulated such that linear
      myotubes are produced. In a previous study, we found that linear arrays of
      myoblasts cultured on micropatterns of laminin fused to form linear myotubes of a
      constant diameter, independent of the width of the laminin track. This suggested
      that a mechanism exists to prevent myoblasts from fusing laterally [Exp. Cell
      Res. 230 (1997) 275]. In this study, we have investigated this further by
      culturing myoblasts on ultrafine grooved surfaces previously shown to align
      fibroblasts and epithelial cells. We found that all the individual myoblasts were
      highly aligned along the groove axis, and time-lapse recordings showed that
      motility was mostly restricted to a direction parallel to the grooves. In
      contrast to the previous study, however, there was a strong tendency for early
      differentiating cells to form aggregates either at an angle of approximately 45
      degrees or perpendicular to the groove axis. Nevertheless, we rarely saw myotubes
      formed at those angles, supporting our earlier idea that the ability of cells to
      fuse laterally is prohibited. Our data strongly suggest that myoblasts are most
      likely to fuse in an end-to-end configuration, and it is this that enables them
      to form linear, rather than irregular myotubes.

PMID- 11950598
TI  - Analysis of the subcellular distribution of avian p95-APP2, an ARF-GAP
      orthologous to mammalian paxillin kinase linker.
AB  - We describe here the identification and characterization of avian p95-APP2, a
      multi-domain protein of a recently identified family of ADP-ribosylation factor
      (ARF)-GTPase-activating proteins (GAPs) including mammalian G protein-coupled
      receptor kinases (GRK)-interactor 1 (GIT1), paxillin kinase linker (PKL), and
      GIT2, as well as avian p95-APP1. The p95-APP2 is eluted from Rac-GTP-gamma-S, but
      not from Rac-GDP-beta-S columns. As other members of the family, p95-APP2 has
      binding regions for the focal adhesion protein paxillin, and for the Rac
      exchanging factor PIX. Sequence comparison indicates that p95-APP2 is the avian
      orthologue of mammalian PKL. Expression studies showed a largely diffuse
      distribution of the full length p95-APP2, without evident effects on cell
      morphology. We observed a dramatic difference between the localization of the
      amino-terminal portion of the protein, including the ARF-GAP domain and the three
      ankyrin repeats, and the carboxy-terminal portion including the paxillin-binding
      site. Moreover, the expression of truncated carboxy-terminal polypeptides
      including both the PIX- and paxillin-binding regions leads to a marked
      localization of the protein together with paxillin at large vesicles. Comparison
      of the expression of corresponding ARF-GAP-deficient constructs from p95-APP2 and
      p95-APP1 shows their distribution at distinct endocytic compartments. Altogether,
      these data support a role of distinct members of this family of ARF-GAPs in the
      regulation of different steps of membrane traffic during cell motility, and
      suggest that p95-APP2 may shuttle between an intracellular compartment and the
      cell periphery, although, further work will be needed to address this point.

PMID- 11950599
TI  - Differentiated HL-60 cells are a valid model system for the analysis of human
      neutrophil migration and chemotaxis.
AB  - We have carried out a detailed comparison of the motile properties of
      differentiated HL-60 cells and human peripheral blood neutrophils. We compared
      the effects of chemotactic stimuli and of inhibitors of signalling proteins on
      morphology, chemokinesis and chemotaxis of neutrophils and differentiated HL-60
      cells using videomicroscopy and a filter assay for chemotaxis. We also assessed
      expression of signalling and cytoskeletal proteins using Western blotting.
      Chemotactic peptide induced a front-tail polarity in HL-60 cells comparable to
      that of neutrophils. Chemokinetic and chemotactic responses to chemotactic
      peptide were also very similar for both cell types, concerning mean speed of
      migration, the fraction of migrated cells and the concentration of stimulus
      optimal for activation. The cytokine interleukin-8 was in contrast clearly less
      effective in activating motile responses of differentiated HL-60 cells as
      compared to neutrophils. An important functional role of Rho-activated kinases
      and phosphatidylinositol 3-kinase in motile responses of HL-60 cells, consistent
      with their upregulation during differentiation, could be confirmed using
      inhibitors with specificity for the corresponding enzymes. The only difference
      observed here between HL-60 cells and neutrophils concerned the differential
      effects of a protein kinase C inhibitor.In summary, the results presented here
      show that differentiated HL-60 cells, stimulated with chemotactic peptide, are a
      valid model system to study molecular mechanisms of neutrophil emigration.

PMID- 11950600
TI  - Roles for the tubulin- and PTP-PEST-binding paxillin LIM domains in cell adhesion
      and motility.
AB  - Cell dynamics mediated through cell-extracellular matrix contacts, such as
      adhesion and motility involve the precise regulation of large complexes of
      structural and signaling molecules called focal adhesions (FAs). Paxillin is a
      multi-domain FA adaptor protein containing five amino-terminal paxillin leucine
      aspartate repeat (LD) motifs and four carboxyl-terminal Lin-11 Isl-1 and Mec-3
      (LIM) domains. The LD motifs support paxillin binding to actopaxin, integrin
      linked kinase (ILK), FA kinase (FAK), paxillin kinase linker (PKL) and vinculin.
      Of the LIM domains, LIM2 and 3 comprise the paxillin FA-targeting motif, with
      phosphorylation of these domains modulating paxillin targeting and cell adhesion
      to fibronectin (Fn). The identity of the paxillin FA targeting partner remains to
      be determined; however, the LIM domains mediate interactions with tubulin and the
      protein-tyrosine phosphatase (PTP)-PEST. PTP-PEST binding requires both LIM3 and
      4, whereas, the precise LIM target of tubulin binding is not known. In this
      report, we demonstrate that the individual paxillin LIM2 and 3 domains support
      specific binding to tubulin and suggest a potential role for this interaction in
      the regulation of paxillin sub-cellular compartmentalization. In addition,
      expression of paxillin molecules with mutations in the tubulin- and PTP-PEST
      binding LIM domains differentially impaired Chinese hamster ovary K1 (CHO.K1)
      cell adhesion and migration to Fn. Perturbation of LIM3 or 4 inhibited adhesion
      while mutation of LIM2 or 4 decreased cell motility. Interestingly, expression of
      tandem LIM2-3 inhibited cell adhesion and spreading while LIM3-4 stimulated a
      well-spread polarized phenotype. These data offer further support for a critical
      role for paxillin in cell adhesion and motility.

PMID- 11950601
TI  - Cloning and characterization of betaCAP73, a novel regulator of beta-actin
      assembly.
AB  - In non-muscle cells, the isoactins are differentially localized, with beta-actin
      specifically enriched at the cell cortex within motile structures, such as
      lamellae, while gamma-actin shows no specific localization. To understand the
      sorting and regulation of beta-actin within moving cells, we previously isolated
      betaCAP73, a novel beta-actin-specific binding protein (Cell Motil. Cytoskel. 35
      (1996) 175). Here, we have cloned and characterized the 4718 nucleotide betaCAP73
      cDNA from an endothelial cell library. betaCAP73 cDNA contains six predicted
      ankyrin-like repeats at the amino terminus and is partially homologous to three
      previously reported sequences of unknown function. Northern analysis reveals
      betaCAP73 expression in all tissues tested, with highest levels in skeletal
      muscle. Consistent with previously demonstrated interactions between native
      betaCAP73 and beta-actin filament barbed-ends, recombinant betaCAP73 inhibits
      pyrene-actin assembly in an isoactin-specific manner. Compared to stationary
      cells betaCAP73 mRNA is down regulated in crawling cells. Similarly, motility
      defective cells have increased betaCAP73 protein. Overexpression of full-length
      betaCAP73 induces the formation of novel membrane protrusions that are enriched
      in betaCAP73, while overexpression of betaCAP73 domains alters cell morphology.
      Combined, these results indicate that betaCAP73 modulates isoactin dynamics to
      regulate the morphological alterations required for cell growth and motility.

PMID- 11950602
TI  - Phenotype modulation in non-adherent and adherent sublines of Walker
      carcinosarcoma cells: the role of cell-substratum contacts and microtubules in
      controlling cell shape, locomotion and cytoskeletal structure.
AB  - We characterised two sublines of Walker carcinosarcoma cells generated by
      epigenetic changes. Subline 1 cells were mostly polarised and made no or only non
      adhesive cell-substratum contacts. Subline 2 cells were spread, adhesive and
      mainly non-polar. Subline 1 cells migrate in a non-adhesive mode which is very
      efficient but operates only in a 3D environment, whereas subline 2 cells migrate
      in an adhesive mode, which is less efficient but works on 2D and 3D substrata.
      Nocodazole had little or no effect on shape, polarity and locomotion of subline 1
      cells. In glass-adherent subline 2 cells, 10(-6)M nocodazole increased the
      proportion of polarised cells migrating in an adhesive mode and decreased
      adhesion to the substratum, whereas 10(-5)M nocodazole further reduced the
      contacts and the cells reverted to a non-adhesive mode of locomotion. When non
      polar subline 2 cells were detached mechanically or by nocodazole, they became
      polarised and morphologically indistinguishable from non-adherent subline 1
      cells. On more adhesive plastic substrata, subline 2 cells produced heterogeneous
      responses to nocodazole including loss of polarity. The phenotypes of Walker
      carcinosarcoma sublines have similarities with a broad range of cell types
      ranging from leucocytes to fibroblast-like cells, suggesting that these
      phenotypic differences can be controlled by the adhesive and contractile state
      rather than the cell type. Adhesion modulates contractility (isometric or
      isotonic contraction) and vice versa and this determines morphology (shape, F
      actin, myosin and alpha-actinin), locomotion and responses to microtubule
      disassembly. The model may be applied to analyse the mechanisms controlling the
      phenotype of cells in general.

PMID- 11950603
TI  - Light perception in plants: cytokinins and red light join forces to keep
      phytochrome B active.
AB  - Plant growth and development is modulated by internal cues such as rhe hormonal
      balance and external factors. Plants are particularly sensitive to their light
      environment, which they scrutinize with at least three classes of photoreceptors.
      In recent years, it has become increasingly clear that light and hormonal
      signaling interact at several levels. A cytokinin receptor was recently
      identified together with several elements acting in this signaling pathway. ARR4,
      a response regulator working downstream of a cytokinin receptor, has been shown
      to regulate phytochrome B-mediated light signaling.

PMID- 11950604
TI  - GARNet, the Genomic Arabidopsis Resource Network.
AB  - GARNet, the Genomic Arabidopsis Resource Network, was created to establish UK
      based facilities for functional genomic research on Arabidopsis thaliana. In
      addition, GARNet provides a platform for international Arabidopsis research and
      for research on other plant species. To use the GARNet facilities apply via the
      website: http://garnet.arabidopsis.org.uk. All GARNet services and resources are
      publicly available, and data created using the GARNet resources will be freely
      distributed via databases held at the Nottingham Arabidopsis Stock Centre and the
      John Innes Centre.

PMID- 11950610
TI  - Cystathionine gamma-synthase and threonine synthase operate in concert to
      regulate carbon flow towards methionine in plants.
AB  - The sulfur-containing amino acid methionine is a nutritionally important
      essential amino acid and is the precursor of several metabolites that regulate
      plant growth and responses to the environment. Methionine production is largely
      regulated by cystathionine gamma-synthase, the first specific enzyme for its
      synthesis. This enzyme competes in a complex manner with threonine synthase, the
      last enzyme in threonine biosynthesis, for their common substrate O
      phosphohomoserine. New genetic and molecular data suggest that methionine
      synthesis and catabolism are coordinately regulated by novel post-transcriptional
      and post-translational mechanisms that are associated with a regulatory part
      within the N-terminal part of cystathionine gamma-synthase.

PMID- 11950611
TI  - A simple nomenclature for a complex proton pump: VHA genes encode the vacuolar
      H(+)-ATPase.
AB  - The vacuolar-type H(+)-ATPase acidifies intracellular compartments and is
      essential for many processes, including cotransport, guard cell movement,
      development, and tolerance to environmental stress. We have identified at least
      26 genes encoding subunits of the vacuolar-type H(+)-ATPase in the Arabidopsis
      thaliana genome, although inconsistent nomenclature of these genes is confusing.
      The pump consists of subunits A through H of the peripheral V(1) complex, and
      subunits a, c, c" and d of the V(o) membrane sector. Most V(1) subunits are
      encoded by a single gene, whereas V(o) subunits are encoded by multiple genes
      found in duplicated segments of the genome. We propose to name these genes VHA-x,
      where x represents the letter code for each subunit. Applying a consistent
      nomenclature will help us to understand how the expression, assembly and activity
      of this pump are integrated with plant growth, signaling, development and
      adaptation.

PMID- 11950612
TI  - Cluster roots--an underground adaptation for survival in extreme environments.
AB  - Cluster roots are a characteristic of members of the Proteaceae and of several
      other plant species that are adapted to habitats of extremely low soil fertility,
      usually without formation of mycorrhizal associations. Functionally linked with
      intense mobilization of nutrients (P, Fe, Zn, Mn) by root-induced chemical
      changes (pH, root exudates, redox potential) in the rhizosphere, cluster-rooted
      plant species can serve as model plants to study rhizosphere processes and
      regulatory aspects of plant adaptations for chemical mobilization of nutrients in
      the rhizosphere.

PMID- 11950613
TI  - Cation channels in the Arabidopsis plasma membrane.
AB  - In vivo analyses have identified different functional types of ion channels in
      various plant tissues and cells. The Arabidopsis genome contains approximately 70
      genes for ion channels, of which 57 might be cation-selective channels (K(+),
      Ca(2+) or poorly discriminating channels). Here, we describe the different
      families of (putative) cation channels: the Shakers, the two-P-domain and Kir
      K(+) channels (encoded by the KCO genes), the cyclic-nucleotide-gated channels,
      the glutamate receptors, and the Ca(2+) channel TPC1. We also compare molecular
      data with the data obtained in planta, which should lead to a better
      understanding of the identity of these channels and provide clues about their
      roles in plant nutrition and cell signalling.

PMID- 11950614
TI  - Does complexity constrain organelle evolution?
AB  - The evolution of eukaryotes was punctuated by invasions of the bacteria that have
      evolved to mitochondria and plastids. These bacterial endosymbionts founded major
      eukaryotic lineages by enabling them to carry out aerobic respiration and
      oxygenic photosynthesis. Yet, having evolved as free-living organisms, they were
      at first poorly adapted organelles. Although mitochondria and plastids have
      integrated within the physiology of eukaryotic cells, this integration has
      probably been constrained by the high level of complexity of their bacterial
      ancestors and the inability of gradual evolutionary processes to drastically
      alter complex systems. Here, I review complex processes that directly involve
      translation of plastid mRNAs and how they could constrain transfer to the nucleus
      of the genes encoding them.

PMID- 11950615
TI  - The Z-scheme--down hill all the way.
AB  - The Z-scheme is considered in the context of personal recollections of events
      during the time that it was conceived and an evaluation of its enduring
      importance.

PMID- 11950622
TI  - Uric acid and cardiovascular risk.
AB  - Uric acid has long been associated with cardiovascular disease. Most
      epidemiological evidence suggests a significant, graded, independent and specific
      association between the level of serum uric acid and cardiovascular morbidity and
      mortality. This is particularly robust among persons at high cardiovascular risk,
      including those with hypertension, diabetes and congestive heart failure.
      Although several potential mechanisms have been identified to explain this
      association, as yet there is no evidence that uric acid bears a causal or
      reversible relationship to vascular disease.

PMID- 11950621
TI  - Oxygen radicals in cardiovascular-renal disease.
AB  - Oxidative stress is associated with diabetes mellitus and hypertension. Recent
      studies suggest that oxygen radicals contribute to the enhanced basal vascular
      tone, tubuloglomerular feedback, monocyte/macrophage infiltration and sensitivity
      of the vasculature and to the impaired endothelium-dependent relaxation in the
      diseased kidney. Pharmacological antioxidants can decrease oxidative stress,
      improve renal vascular function and decrease blood pressure in cardiovascular
      renal disease.

PMID- 11950623
TI  - Vasopeptidase inhibitors: a new class of dual zinc metallopeptidase inhibitors
      for cardiorenal therapeutics.
AB  - Vasopeptidase inhibitors are a new class of drugs that simultaneously inhibit
      angiotensin-I-converting enzyme and neutral endopeptidase 24.11, two
      metallopeptidases responsible for the breakdown of different vasoactive peptides.
      At least ten vasopeptidase inhibitors are in various stages of development and
      results obtained in preclinical and clinical studies indicate a promising future
      for the treatment of hypertension, heart failure and renal disease. However, like
      angiotensin-I-converting-enzyme inhibitors, vasopeptidase inhibitors are
      characterized by acute and chronic side-effects that need to be clarified.

PMID- 11950625
TI  - Current treatment and future directions in heart failure.
AB  - Recent research in the pathophysiology of congestive heart failure has focused on
      the blockade of neurohormonal systems. Large clinical trials have clearly
      demonstrated morbidity and mortality benefits of angiotensin-converting-enzyme
      inhibitors and beta blockers. Indeed, all patients with heart failure should be
      treated with these agents unless there is a specific contraindication otherwise.
      Despite this treatment, however, mortality from heart failure remains high.
      Current investigation is now focused on other pathophysiological mechanisms and
      the interruption of these pathways.

PMID- 11950624
TI  - B-type natriuretic peptide for the treatment of congestive heart failure.
AB  - Since their discovery 20 years ago, the natriuretic peptides have emerged as an
      important endocrine response to excessive increases in intravascular volume. In a
      cGMP-dependent fashion, the natriuretic peptides induce a balanced vasodilation,
      decreasing preload and afterload in states of cardiac impairment and stimulating
      the excretion of salt and water by the kidneys. Recombinant B-type natriuretic
      peptide (nesiritide), identical to the principle natriuretic peptide produced by
      human cardiac ventricles, has just been approved for the treatment of acute
      decompensated congestive heart failure. Nesiritide has been shown in controlled
      trials in congestive heart failure to decrease pulmonary capillary wedge
      pressure, improve cardiac output, stimulate natriuresis and diuresis, and rapidly
      induce symptomatic relief. As a naturally occurring stress hormone of the heart,
      with particular rectifying effects on the pulmonary, cardiac and renal
      vasculatures, B-type natriuretic peptide may prove useful in a variety of
      cardiovascular disease states.

PMID- 11950626
TI  - Recent advances in arrhythmia therapy: treatment and prevention of atrial
      fibrillation.
AB  - Current therapy for atrial fibrillation is divided into rhythm control agents and
      rate control agents. Although class III antiarrhythmic agents are being used
      increasingly for both conversion of atrial fibrillation to sinus rhythm and
      prevention of recurrence, most pharmacological approaches under active
      investigation, including azimilide and dronedarone, are compounds with multiple
      electrophysiological actions. Based on the current knowledge of the mechanisms
      involved in atrial fibrillation initiation and maintenance, novel approaches
      targeting the intracellular calcium overload are being investigated.

PMID- 11950627
TI  - Utility of point-of-care diagnostic testing in patients with chest pain and
      suspected acute myocardial infarction.
AB  - Advances over the past few years have led to the use of hand-held point-of-care
      diagnostic tests to expedite testing for cardiac enzymes indicative of acute
      myocardial infarction. Although cardiac enzymes such as troponin I and CKMB are
      reliable markers of acute myocardial infarction, they cannot be detected until
      several hours after the insult and patients are often tested for up to 24 hours
      before acute myocardial infarction can be ruled out. A better understanding of
      early events in thrombus formation, specifically the role of P-selectin in
      platelet aggregation, should soon allow even more rapid diagnosis and improve
      pharmacological treatment. In addition, early ruling-out of patients with non
      cardiac chest pain would reduce unnecessary hospital admissions and associated
      healthcare costs.

PMID- 11950628
TI  - Adenosine A1 receptor antagonists in the kidney: effects in fluid-retaining
      disorders.
AB  - Adenosine A(1) receptor antagonists have been used effectively as potassium
      sparing and renal-function-protective diuretics in new studies. In addition, the
      role of adenosine--acting through adenosine A(1) receptors--in renal
      autoregulation has been clarified. Finally, the application of adenosine receptor
      antagonists has been implicated in protection from acute renal failure associated
      with radiocontrast media treatment.

PMID- 11950629
TI  - Disorders of phosphate metabolism in chronic renal disease.
AB  - Hyperphosphatemia directly or indirectly contributes to the progression of
      chronic renal disease and is an important factor in the development of secondary
      hyperparathyroidism and uremic bone disease. New therapeutic advances include the
      development of calcium-free intestinal phosphate binders, calcimimetics to
      control parathyroid hormone secretion and non-calcemic vitamin D analogs.

PMID- 11950630
TI  - Therapeutic strategies to halt renal fibrosis.
AB  - Angiotensin II blockade has become a standard anti-fibrotic therapy in renal
      diseases because it slows progression to end-stage renal disease. However,
      current data support the notion that angiotensin II blockade alone cannot stop
      progressive fibrotic disease. Of an increasing number of therapies showing
      efficacy in animal studies, antibodies to transforming growth factor beta are the
      most thoroughly studied and are likely to be effective in human clinical trials.
      However, hints exist in the literature suggesting that no single agent will
      effectively halt renal fibrosis and that combinations of agents will be required.

PMID- 11950631
TI  - Treatment of type 2 diabetic nephropathy by blockade of the renin-angiotensin
      system: a comparison of angiotensin-converting-enzyme inhibitors and angiotensin
      receptor antagonists.
AB  - Type 2 diabetes is the most prevalent form of diabetes mellitus worldwide and
      associated diabetic nephropathy is the most common cause of end-stage renal
      disease in the USA. Lowering blood pressure and controlling glucose slows the
      progression to end-stage renal disease or death. Although angiotensin-converting
      enzyme inhibitors reduce proteinuria, their effects to slow progression to end
      stage renal disease have not been clearly demonstrated in type 2 diabetic
      nephropathy. Recent clinical trials with angiotensin AT(1) receptor antagonists
      demonstrate that they reduce proteinuria, stabilize renal function and slow the
      progression of nephropathy to end-stage renal disease in patients with type 2
      diabetes. These are significant benefits beyond those associated with
      conventional therapy and blood pressure control.

PMID- 11950632
TI  - Advances in our understanding of aging: role of the renin-angiotensin system.
AB  - Knowledge about the pathophysiological role of the renin-angiotensin system is
      constantly improving and its relationship with mechanisms of oxidative stress
      suggests its possible involvement with the deleterious effects of aging. Recent
      data opens a new field of investigation in this area.

PMID- 11950633
TI  - The potential value of iron oxide nanoparticles in brain tumor treatment.

PMID- 11950634
TI  - Subcortical low-intensity areas on T2-weighted images: an uncommon finding with a
      common explanation?

PMID- 11950635
TI  - How can we make BOLD contrast bolder?

PMID- 11950636
TI  - Intraosseous venography during percutaneous vertebroplasty: is it needed?

PMID- 11950637
TI  - Comparison of two superparamagnetic viral-sized iron oxide particles ferumoxides
      and ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors.
AB  - BACKGROUND AND PURPOSE: Ultrasmall superparamagnetic iron oxide particles result
      in shortening of T1 and T2 relaxation time constants and can be used as MR
      contrast agents. We tested four hypotheses by evaluating MR images of
      intracranial tumors after infusion of two iron oxide agents in comparison with a
      gadolinium chelate: 1) Ferumoxtran in contrast to ferumoxides can be used as an
      intravenous MR contrast agent in intracranial tumors; 2) ferumoxtran enhancement,
      albeit delayed, is similar to gadolinium enhancement; 3) ferumoxtran-enhanced MR
      images in contrast to gadolinium-enhanced MR images may be compared with
      histologic specimens showing the cellular location of iron oxide particles; 4)
      ferumoxtran can serve as a model for viral vector delivery. METHODS: In 20
      patients, ferumoxides and ferumoxtran were intravenously administered at
      recommended clinical doses. MR imaging was performed 30 minutes and 4 hours after
      ferumoxides infusion (n = 3), whereas ferumoxtran-enhanced MR imaging (n = 17)
      was performed 6 and 24 hours after infusion in the first five patients and 24
      hours after infusion in the remaining 12. MR sequences were spin-echo (SE) T1
      weighted, fast SE T2- and proton density-weighted, gradient-recalled-echo T2*
      weighted, and, in four cases, echo-planar T2-weighted sequences. Representative
      regions of interest were chosen on pre- and postcontrast images to compare each
      sequence and signal intensity. RESULTS: Despite some degree of gadolinium
      enhancement in all tumors, no significant T1 or T2 signal intensity changes were
      seen after ferumoxides administration at either examination time. Fifteen of 17
      patients given ferumoxtrans had T1 and/or T2 shortening consistent with iron
      penetration into tumor. Histologic examination revealed minimal iron staining of
      the tumor with strong staining at the periphery of the tumors. CONCLUSION: 1)
      Ferumoxtran can be used as an intravenous MR contrast agent in intracranial
      tumors, mostly malignant tumors. 2) Enhancement with ferumoxtran is comparable to
      but more variable than that with the gadolinium chelate. 3) Histologic
      examination showed a distribution of ferumoxtran particles similar to that on MR
      images, but at histology the cellular uptake was primarily by parenchymal cells
      at the tumor margin. 4) Ferumoxtran may be used as a model for viral vector
      delivery in malignant brain tumors.

PMID- 11950638
TI  - Diffusion tensor MR imaging of high-grade cerebral gliomas.
AB  - BACKGROUND AND PURPOSE: Optimizing high-grade glioma treatment requires the
      delineation of edematous and normal brain from tumor, perhaps by using potential
      differences in the absolute diffusion parameters of water. Our purpose was to
      determine whether mean diffusivity <D> and diffusion anisotropic MR imaging data
      help in this differentiation. METHODS: Nine patients with high-grade cerebral
      glioblastoma underwent contrast-enhanced structural and diffusion tensor MR
      imaging before therapy. Tumor, edematous brain, and apparently normal white
      matter regions were determined on T2-weighted and contrast-enhanced T1-weighted
      structural images. Fractional anisotropy (FA) and <D> were measured in each
      tissue type. Differences in these values among the tissue types were assessed
      with a standard analysis of variance. RESULTS: <D> was highest in the necrotic
      tumor core (1825.38 +/-404.06) x 10(-6) mm(2)/s, followed by edematous brain
      (1411.23 +/- 322.31) x 10(-6) mm(2)/s, enhancing tumor core (1308.67 +/- 292.50)
      x 10(-6) mm(2)/s, enhancing tumor margin (1229.80 +/- 206.80) x 10(-6) mm(2)/s,
      and normal brain (731.53 +/- 35.21) x 10(-6) mm(2)/s. FA was highest in normal
      brain (0.47 +/- 0.08) and lowest in the necrotic core (0.09 +/- 0.03). <D> was
      significantly different in enhancing tumor margins and edematous brain in all
      patients; FA was significantly different in only seven. These values were
      significantly different from those of normal brain in all cases in which they
      were measurable. CONCLUSION: <D> values can be used to differentiate normal white
      matter, edematous brain, and enhancing tumor margins. Diffusion anisotropic data
      added no benefit to tissue differentiation. Further studies are required to
      determine if a <D> value that corresponds to the limit of tumor invasion can be
      identified.

PMID- 11950639
TI  - Preoperative location of the pituitary bright spot in patients with pituitary
      macroadenomas.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the location
      of the pituitary bright spot in patients with pituitary macroadenomas before
      surgery. METHODS: A total of 54 patients with pituitary macroadenomas were
      retrospectively included in this study. Nonenhanced spin-echo T1-weighted MR
      images were reviewed to identify the location of the high-intensity-signal
      posterior pituitary lobe that indicates antidiuretic hormone (ADH) storage.
      Images were acquired with a 1.5-T machine by using 3-mm-thick contiguous sections
      in two or three orthogonal planes and a 300 x 512 matrix. RESULTS: The bright
      spot corresponding to ADH storage was identified in 44 (81%) patients. Two groups
      of patients were defined by the height of the macroadenoma: Group A patients (n =
      27) had pituitary macroadenomas less than 20 mm in height, and group B (n = 27)
      had macroadenomas 20 mm or larger. In group A, the bright spot was identified in
      25 patients (93%); it was located in the sella in 24 of these cases (96%). In
      group B, the bright spot was identified in 19 patients (70%); it was in an
      ectopic location in 14 of these cases (74%). CONCLUSION: MR imaging can be used
      to depict the pituitary bright spot in most patients with pituitary macroadenomas
      before surgery. The bright spot is usually identified at its expected location
      within the sella in patients with pituitary macroadenomas less than 20 mm in
      height, whereas an ectopic location is common when pituitary macroadenomas are
      larger more than 20 mm.

PMID- 11950640
TI  - Brainstem involvement with mycosis fungoides: an unusual central nervous system
      complication.
AB  - Changes in the brainstem were demonstrated with MR imaging in a patient with
      mycosis fungoides. Previous reports of CNS involvement in this rare disease have
      not had similar findings.

PMID- 11950641
TI  - Subcortical low intensity on MR images of meningitis, viral encephalitis, and
      leptomeningeal metastasis.
AB  - BACKGROUND AND PURPOSE: Subcortical low-intensity lesion on T2-weighted images is
      an uncommon manifestation of ischemia, multiple sclerosis, and Sturge-Weber
      disease. This study was performed to determine whether subcortical low signal
      intensity is an MR feature of meningitis, viral encephalitis, or leptomeningeal
      metastasis and to investigate a cause of subcortical low intensity. METHODS: We
      retrospectively reviewed MR images of 117 patients with meningitis, encephalitis
      (viral or unknown), or leptomeningeal metastasis for the presence of subcortical
      low intensity, meningeal enhancement, signal intensity change of cortex, and
      change in subcortical low intensity on follow-up images. Diffusion-weighted (DW)
      images and apparent diffusion coefficient (ADC) maps were obtained in 55
      patients. Subcortical low-intensity lesions were also quantitatively analyzed on
      T2-weighted, fluid-attenuated inversion recovery (FLAIR), and DW images. RESULTS:
      Subcortical low intensity was found in nine (23.7%) of 38 patients with
      encephalitis (viral, 31; unknown origin, 7), five (24%) of 21 with leptomeningeal
      metastasis, and five (9%) of 58 with meningitis. Leptomeningeal enhancement was
      observed in 100% and cortical hyperintensity in 14 (74%) of 19 patients with
      subcortical low intensity. Leptomeningeal enhancement was seen in 46 (47%) and
      cortical hyperintensity in 33 (34%) of 98 patients without subcortical low
      intensity. Subcortical low intensity disappeared or decreased in extent on follow
      up MR images in all seven patients who underwent follow-up. ADC of subcortical
      low-intensity lesions was lower than that of the contralateral area and decreased
      by 9.3 +/- 11.4%. CONCLUSION: Subcortical low intensity was uncommonly found in
      meningitis, viral encephalitis, and leptomeningeal metastasis. It is a
      nonspecific MR sign of various meningeal and cortical diseases. Although the
      cause of subcortical low intensity remains uncertain, free radical formation may
      play a role as a causative factor.

PMID- 11950643
TI  - Emerging patterns of diffusion-weighted MR imaging in Creutzfeldt-Jakob disease:
      case report and review of the literature.
AB  - We report the use of diffusion-weighted MR imaging in the early diagnosis and
      monitoring of the progression of a histopathologically proved case of sporadic
      Creutzfeldt-Jakob disease. Ribbon-like areas of hyperintensity in the cerebral
      cortex on diffusion-weighted images corresponded to the localization of periodic
      sharp-wave complexes on the electroencephalogram.

PMID- 11950642
TI  - Correlation between percentage of brain parenchymal volume and neurocognitive
      performance in HIV-infected patients.
AB  - BACKGROUND AND PURPOSE: This study was designed to determine whether
      neuropsychological function in HIV-infected persons is correlated with loss of
      brain volume (as measured by percentage of brain parenchymal volume [PBV]). We
      hypothesized that whole-brain parenchymal volume might correlate with
      neuropsychologic performance, even before overt clinical dysfunction is apparent.
      METHODS: A computer-assisted segmentation technique with thin section MR imaging
      was used for 15 patients with HIV infection (seven symptomatic, eight
      asymptomatic) and for five HIV-negative control participants to quantify whole
      brain and CSF volumes. To determine the degree of brain atrophy, the PBV relative
      to that of intracranial content was calculated. Neuropsychological performance
      was assessed by using a standard battery of eight tests (NPZ-8 test battery).
      RESULTS: HIV-infected patients had significantly lower NPZ-8 scores (t[18] =
      2.26, P <.05) and lower PBV (t[18] = 1.79, P <.01) than those of healthy control
      participants. With the Spearman rank order correlation coefficients, data
      analyzed for all 20 study participants (15 HIV-infected patients and five
      noninfected control participants) showed a significant (r = -0.50, P <.05)
      negative correlation between PBV and NPZ-8 test battery score. In addition, there
      was a significant negative correlation between subtest score of motor impairment
      and PBV (r = -0.69, P <.01) and between AIDS dementia complex score (r = -0.64)
      and PBV (P <.01). CONCLUSION: These correlations suggest that quantitation of PBV
      may offer an objective, easily acquired surrogate predictor of neuropsychological
      impairment and clinically apparent cognitive/motor dysfunction among HIV-infected
      persons.

PMID- 11950644
TI  - Comparison of pre- and postcontrast 3D time-of-flight MR angiography for the
      evaluation of distal intracranial branch occlusions in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Three-dimensional time-of-flight (TOF) MR angiography is
      used routinely in stroke workup to detect arterial occlusions, but a major
      drawback is its inadequate depiction of vessels with slow or in-plane flow. We
      hypothesized that the use of contrast-enhanced MR angiography improves
      delineation of vessels with diminished or absent flow on precontrast MR
      angiograms. METHODS: Pre- and postcontrast 3D TOF MR angiograms were acquired in
      55 consecutive patients with acute stroke. Patency of 480 intracranial vessels
      was assessed on both the pre- and postcontrast angiograms. Diffusion-weighted
      (DW) and perfusion-weighted (PW) imaging data were also obtained and results
      correlated with those of pre- and postcontrast MR angiography. RESULTS: For 50
      abnormal vessel segments seen on precontrast MR angiograms, postcontrast MR
      angiograms resulted in change in the vascular signal intensity in 70% (35 vessel
      segments); 94% of these changes showed a greater extent of vessel patency. Venous
      and soft-tissue contrast enhancement had no effect on assessment in 95% of all
      480 vessels examined. Interobserver reliability was moderate, with postcontrast
      interpretation (kappa = 0.48) showing a slight improvement over precontrast
      interpretation (kappa = 0.41). Good agreement was found between the TOF results
      and the pooled DW and PW imaging results. CONCLUSIONS: Compared with precontrast
      3D TOF MR angiograms, postcontrast 3D TOF angiograms improve assessment of
      intracranial vessel patency in acutely ischemic vascular territories. In some
      patients, an improved understanding of acute ischemic stroke was obtained by
      viewing the pre- and postcontrast images. Postcontrast MR angiography should be
      included in the MR evaluation of acute stroke.

PMID- 11950645
TI  - Relationship between findings of conventional and contrast-enhanced transcranial
      color-coded real-time sonography and angiography in patients with basilar artery
      occlusion.
AB  - BACKGROUND AND PURPOSE: Contrast-enhanced transcranial color-coded real-time
      sonography (TCCS) is a promising tool for the evaluation of brain circulation.
      The purpose of the present study was to assess the diagnostic ability of
      conventional and contrast-enhanced TCCS in patients with acute stroke and basilar
      artery occlusion and to compare the findings with those of angiography. METHODS:
      We prospectively performed conventional and contrast-enhanced TCCS within 3 days
      before or after digital subtraction angiography or MR angiography in 62
      consecutive patients with acute ischemic stroke. We assigned the patients to two
      groups on the basis of angiographic findings: basilar artery occlusion group (n =
      7) and control group without basilar artery occlusion (n = 55). We obtained
      basilar artery flow images showing the direction of blood flow using TCCS through
      a suboccipital window. RESULTS: In the control group, the detection rate of
      basilar artery flow using conventional and contrast-enhanced TCCS was 76.4% and
      98.2%, respectively (P <.001), and the flow direction was antegrade in all
      patients. In the basilar artery occlusion group, neither conventional nor
      contrast-enhanced TCCS could obtain flow images of the proximal basilar artery in
      any patient. In five patients with proximal basilar artery occlusion, a reversed
      flow image in the distal basilar artery obtained by contrast-enhanced TCCS was
      confirmed by angiography to be blood supply through collateral circulation from
      the carotid systems. However, two patients with distal basilar artery occlusion
      did not have this sign. CONCLUSION: Contrast-enhanced TCCS is more sensitive in
      imaging basilar artery flow than is conventional TCCS. When examined with
      contrast-enhanced TCCS, a combination of absent basilar artery flow and the
      reversed basilar artery flow sign may be a diagnostic indicator of basilar artery
      occlusion.

PMID- 11950646
TI  - Time-threshold curve determined by single photon emission CT in patients with
      acute middle cerebral artery occlusion.
AB  - BACKGROUND AND PURPOSE: In patients with ischemic stroke, not only the degree of
      ischemia but also its duration are key determinants of tissue survival. The
      purpose of this study was to show the synergistic effects of these two factors on
      tissue survival in humans. METHODS: We retrospectively reviewed findings in 19
      patients with middle cerebral artery occlusion who had clearly defined ischemic
      duration from onset to angiographic complete recanalization and who underwent
      pretreatment single photon emission CT. Pretreatment single photon emission CT
      and final CT scans were compared, and hypoperfusion cortices were divided into
      reversible and irreversible ischemia. Regions of interest were placed in both
      irreversible and reversible ischemic cortices, and the residual cerebral blood
      flow was analyzed by side-to-side comparison with a calculated asymmetry index.
      To show the relationship between the reversibility of ischemia and the ischemic
      duration/severity, discriminant analyses were conducted. The analyses were
      conducted separately using data obtained within 3 hours of ischemic duration and
      data obtained more than 3 hours after ischemic duration. RESULTS: Within 3 hours
      of ischemic duration, analysis revealed a discriminant line of asymmetry index
      (%) = 21.53 time (h) - 19.15. After more than 3 hours of ischemic duration, it
      revealed a discriminant line of asymmetry index = 0.50 time + 48.27. These
      discriminant lines rose rapidly within the first 3 hours after stroke onset and
      thereafter reached almost a plateau level. CONCLUSION: These pilot data suggest
      urgency for treatment, less need for triage based on cerebral blood flow
      measurement during the first few hours, and more time to triage based on cerebral
      blood flow measurement for patients with later presentations.

PMID- 11950647
TI  - Experimental model of dissecting aneurysms.
AB  - BACKGROUND AND PURPOSE: The pathogenesis and optimal treatment for arterial
      dissection are still unclear. We devised an experimental model of arterial
      dissection and observed the morphologic changes with angiography. METHODS: Sixty
      four experimental dissections were created in the common carotid arteries of 34
      mongrel dogs. After a small incision was made in the arterial adventitia, it was
      dissected from the media. Elliptical defects (2, 4, 6, and 8 mm in groups I-A, I
      B, I-C, and I-D, respectively; n = 47) or longitudinal incisions (4, 6, and 8 mm
      in groups II-A, II-B, and II-C, respectively; n = 17) were made in the intima
      distal to the adventitial incision to serve as an entry zone for dissection.
      RESULTS: Immediately after the lesions were created, the influx of blood into the
      dissected cavity produced massive subadventitial hematomas, resulting in stenotic
      changes in all of the arteries, including seven with occlusion. Follow-up (1
      week) angiograms demonstrated complete healing, with normal arterial calibers in
      11 (79%) of 14 I-A lesions and aneurysm formation in nine (69%) of 13 I-B
      lesions. All 10 I-D lesions had complete arterial occlusion. Persistent stenosis
      was observed in all 10 I-C lesions; six of these developed aneurysms. Pathologic
      examination of the freshly dissected cavities revealed a clot-filled cleft
      between the media and adventitia. Mature aneurysms, evaluated 3 mo later, had
      endothelialization within the aneurysmal dome. CONCLUSION: Morphologic changes
      after arterial dissection are closely related to the size of the intimal entry
      zone, which may determine whether a dissecting aneurysm forms.

PMID- 11950648
TI  - Angiographic and embryologic considerations in five cases of middle cerebral
      artery fenestration.
AB  - Five cases of unilateral middle cerebral artery fenestration were observed during
      the prospective evaluation of 1466 consecutive cerebral angiograms (0.43% of 1170
      patients) between January 1999 and July 2001. In each case, an early branching
      temporopolar artery was seen to arise from the inferior limb of the fenestrated
      segment. This finding suggests that early branching temporopolar arteries may
      participate in the formation of middle cerebral artery fenestration by
      interfering with the normal fetal development of the middle cerebral artery.

PMID- 11950649
TI  - Systemic theophylline augments the blood oxygen level-dependent response to
      forepaw stimulation in rats.
AB  - BACKGROUND AND PURPOSE: Functional MR imaging with blood oxygen level-dependent
      (BOLD) contrast enhancement is believed to rely on changes in cerebral blood flow
      and deoxyhemoglobin level to estimate the location and degree of neural
      activation. We studied the relationship between neural activation and the
      observed BOLD response by using theophylline, an antagonist of the inhibitory
      neurotransmitter adenosine and a potent inhibitor of the vasodilatory response to
      neural activation. METHODS: Using a rat model with electrical forepaw
      stimulation, we performed fMRI measurements before and after the systemic
      injection of either theophylline (0.1 mmol/kg) or an equivalent volume of saline.
      Changes in the BOLD response were quantified by determining the number of
      activated voxels and the amplitude of the BOLD response for each animal in the
      theophylline and saline groups. RESULTS: The theophylline group had a
      significantly Tincreased BOLD response (70-150% increased activated voxel count
      and 60-65% increased BOLD response amplitude) at 45 and 60 minutes after systemic
      injection compared with baseline. The response of the saline-injected control
      group did not change significantly. CONCLUSION: The administration of systemic
      theophylline significantly augmented the BOLD response due to either an elevation
      of resting deoxyhemoglobin levels or the neuroexcitatory effect of theophylline.
      This effect potentially could be used in human fMRI studies to increase the
      sensitivity of the BOLD response.

PMID- 11950650
TI  - Relevance of antecedent venography in percutaneous vertebroplasty for the
      treatment of osteoporotic compression fractures.
AB  - BACKGROUND AND PURPOSE: Controversy exists regarding the utility of antecedent
      venography in percutaneous vertebroplasty. Our purpose was to determine whether
      antecedent venography improves clinical outcomes and/or decreases extravertebral
      cement extravasation in these procedures. METHODS: We retrospective reviewed
      outcomes of consecutive percutaneous vertebroplasty procedures performed at our
      institution to define two populations, each consisting of 24 patients treated at
      42 vertebral levels. Group 1 included patients who underwent antecedent
      venography, and group 2 included patients treated without venography. Clinical
      outcomes were assessed with quantitative measurements of pain and mobility.
      Venograms and postprocedural radiographs were interpreted to evaluate the number
      of vertebrae with extravertebral cement extravasation, degree of extravasation at
      each level, and correlation between venography and vertebroplasty. RESULTS: Pain
      improved in 19 of 20 group 1 patients, compared with 21 of 22 group 2 patients;
      mean postoperative pain levels were 1.3 and 1.8, respectively (P =.50), on a
      scale of 0 (no pain) to 10 (worst pain). All 11 group 1 patients with impaired
      preoperative mobility reported postoperative improvement, as did all 12 group 2
      patients; mean levels of postoperative impaired mobility for groups 1 and 2 were
      0.35 and 0.27, respectively (P =.43). Twenty-two of 42 vertebrae treated in group
      1 demonstrated extravasation, compared with 28 of 42 in group 2 (P =.266);
      amounts of extravasation did not differ. Among 22 levels of extravasation in
      group 1, venograms in 14 showed correlative extravasation. CONCLUSION: Antecedent
      venography does not significantly improve the effectiveness or safety of
      percutaneous vertebroplasty performed by qualified, experienced operators.

PMID- 11950651
TI  - Cardiovascular effects of polymethylmethacrylate use in percutaneous
      vertebroplasty.
AB  - BACKGROUND AND PURPOSE: Previous investigators have described an association
      between polymethylmethacrylate (PMMA) use in hip arthroplasty and cardiovascular
      derangement. Our purpose was to evaluate the effects of PMMA injection on patient
      vital signs during percutaneous vertebroplasty. METHODS: We retrospectively
      reviewed patient charts at our institution to gather blood pressure, heart rate,
      and arterial oxygen saturation data for the following time points: before,
      during, 5 minutes after, and 10 minutes after PMMA injection during percutaneous
      vertebroplasty. These data were obtained for 142 injections (78 patients), and
      preinjection vital signs were compared with vital signs during and after PMMA
      injection. Multivariable regression modeling was used to ascertain the effects of
      cardiopulmonary comorbidities on vital signs. RESULTS: Mean arterial blood
      pressure and heart rate during, 5 minutes after, and 10 minutes after PMMA
      injection were not significantly different from their respective preprocedure
      values (P =.19-.92). Values for oxygen saturation during PMMA injection and 5
      minutes thereafter were not significantly different from preprocedure values (P
      =.80 and.89, respectively). Oxygen saturation was significantly lower at 10
      minutes after injection than before injection (P =.007), although the mean
      difference was negligible (0.6%). CONCLUSION: We find no generalized association
      between PMMA injection during percutaneous vertebroplasty and systemic
      cardiovascular derangement.

PMID- 11950652
TI  - Real-time CT-guided spinal biopsy with a disposable stereotactic device: a
      technical note.
AB  - We compared eight spinal needle biopsy procedures performed with an
      investigational disposable real-time stereotactic device and eight spinal needle
      freehand biopsies in which a standard technique was used, to determine whether
      the investigational device added value to the procedure. The device uses a simple
      stereotactic diaphragm pattern to define two vector points. The procedures in
      which the device was used were completed in 38% less time, using 50% fewer
      images, with considerably improved spatial accuracy and increased operator
      confidence, despite the device learning curve.

PMID- 11950653
TI  - Functional localization of brainstem and cervical spinal cord nuclei in humans
      with fMRI.
AB  - BACKGROUND AND PURPOSE: To our knowledge, no published functional map of the
      human lower brainstem exists. Our purpose was to use 1.5-T functional MR imaging
      (fMRI) to visualize the location of cranial nerve (CN) nuclei and other pontine,
      bulbar, and cervical spinal cord nuclei by using specific sensory stimulation or
      motor performance. METHODS: We localized nuclei by using cross-correlation
      analysis of regional blood oxygen level-dependent (BOLD) signal intensity during
      specific motor and sensory procedures based on known functions of specific
      nuclei. Statistical parametric mapping (SPM) analysis was used for comparison.
      Head, cardiac, and respiratory motion artifact correction was applied. Histologic
      atlases aided localization. RESULTS: We obtained evidence of localization of the
      following nuclei by using tests, as follows: main trigeminal sensory (CN V),
      brushing the face; abducens (CN VI), left-right eye movement; facial (CN VII),
      smiling and lip puckering; hypoglossal (CN XII), pushing the tongue against the
      hard palate; nucleus ambiguus, swallowing; nucleus tractus solitarii (NTS),
      tasting a sweet-sour-salty-bitter mixture; nucleus cuneatus, finger tapping; and
      cervical spinal cord levels C1-C3, tongue movement to activate the strap muscles.
      Activation of cortical motor and sensory areas and somatosensory thalamus
      corresponded with the tasks and sites of brainstem activation. Head movement was
      minimal, typically less than 1 mm in all three axes. CONCLUSION: With 1.5-T fMRI,
      the CN nuclei of the pons and medulla, and other nuclei of the lower brainstem
      and cervical spinal cord, can be localized in awake humans with specific sensory
      stimulation or motor performance.

PMID- 11950655
TI  - Symptomatic enlarged cervical anterior epidural venous plexus in a patient with
      Marfan syndrome.
AB  - A 38-year-old man with Marfan syndrome presented with headache and neck pain. MR
      imaging revealed a large enhancing mass in the cervical anterior epidural space.
      Cervical laminectomy with biopsy of the lesion revealed a large engorged anterior
      epidural venous plexus (AEVP). Marfan syndrome may predispose the patient to
      enlargement of AEVP secondary to a vessel wall abnormality.

PMID- 11950654
TI  - Intracranial hypotension as a cause of radiculopathy from cervical epidural
      venous engorgement: case report.
AB  - We describe the case of a 40-year-old man with spontaneous intracranial
      hypotension who presented with cervical radiculopathy associated with epidural
      venous engorgement. Epidural venous engorgement can occur secondary to
      intracranial hypotension and manifests intracranially as pachymeningeal venous
      engorgement. In the cervical spine, two cases of epidural venous engorgement due
      to intracranial hypotension have been reported in the literature, and neither
      patient presented with symptoms related to nerve compression. Epidural venous
      engorgement should be considered in the differential diagnosis of an enhancing
      epidural mass in the cervical spine. Diagnostic clues include sparing of the
      anterior midline and posterior aspects of the epidural space and, if present,
      pulsation artifact.

PMID- 11950656
TI  - Laron syndrome abnormalities: spinal stenosis, os odontoideum, degenerative
      changes of the atlanto-odontoid joint, and small oropharynx.
AB  - BACKGROUND AND PURPOSE: Patients with Laron syndrome have an inborn growth
      hormone resistance. We investigated abnormalities in the upper airways and
      cervical spine in patients with Laron syndrome. METHODS: We prospectively
      examined 11 patients (one child aged 9 years and 10 adults aged 36-68 years), 10
      of whom underwent MR imaging of the spine or head; nine, radiography of the
      cervical spine; and four, CT of C1-C2. The width of the spinal canal was
      evaluated visually and quantitatively and compared with reference values. The
      smallest diameter of the oropharynx and the thickness of the palate were measured
      and compared with reference values. Nine age-matched female patients referred for
      MR imaging for unrelated reasons served as control subjects. RESULTS: Cervical
      spinal stenosis was present in seven of the adult patients, within a confidence
      interval of 95%. Anomaly of the dens compatible with os odontoideum was present
      in three patients, causing focal myelomalacia in two. The atlanto-odontoid joint
      showed osteoarthritic changes in six of the adult patients. The mediolateral
      diameter of the oropharynx was significantly smaller in the patients with Laron
      syndrome than in the control subjects (P <.005). There was no difference in the
      thickness of the soft palate. CONCLUSION: Patients with Laron syndrome develop
      significant narrowing of the cervical spinal canal and early degenerative changes
      of the atlanto-odontoid joint. Laron syndrome is associated with os odontoideum
      causing myelomalacia. The dimensions of the oropharynx are small. Patients may be
      prone to neurologic morbidity and sleep disturbances. Routine MR imaging of the
      cervical spine is recommended in these patients.

PMID- 11950658
TI  - Imaging findings of cochlear nerve deficiency.
AB  - BACKGROUND AND PURPOSE: High-resolution T2-weighted fast spin-echo MR imaging
      provides excellent depiction of the cisternal and intracanalicular segments of
      the vestibulocochlear and facial nerves. Absence or reduction in caliber of the
      cochlear nerve (deficiency) has been described in association with congenital
      sensorineural hearing loss (SNHL). Depiction of cochlear nerve integrity may be
      important for diagnosis and management of SNHL. METHODS: We retrospectively
      reviewed high-resolution T2-weighted fast spin-echo MR images of 22 patients
      examined for SNHL who had deficiency of the cochlear nerve. Images were evaluated
      for the presence and comparative size of the component nerves (facial, cochlear,
      superior vestibular, and inferior vestibular nerves), relative size of the
      internal auditory canal (IAC), and any associated inner ear abnormalities. The
      clinical history, results of the clinical examination, and audiometric findings
      were reviewed for each patient. RESULTS: Deficiency of the cochlear nerve was
      observed in 12 patients with congenital SNHL and in 10 patients with acquired
      SNHL. Hypoplasia of the IAC was observed in association with congenital
      deficiency of the cochlear nerve in 11 of 12 patients. Deficiency of the cochlear
      nerve was observed in association with acoustic schwannoma in two cases and with
      acquired labyrinthine abnormalities in seven cases. Hypoplasia of the IAC was not
      observed in association with acquired SNHL. CONCLUSION: Deficiency of the
      cochlear nerve can be shown by high-resolution T2-weighted fast spin-echo MR
      imaging. Deficiency may be observed in association with congenital or acquired
      SNHL and may be important in the assessment of patients for cochlear
      implantation. Hypoplasia of the IAC is an indicator of congenital cochlear nerve
      deficiency.

PMID- 11950657
TI  - Radiculomyelitic rabies: can MR imaging help?
AB  - Radiculomyelitic (silent) rabies and acute disseminated encephalomyelitis have
      similar clinical presentations but distinct management and prognostic
      implications. It is thus important to differentiate between the two antemortem.
      Because of their distinct pathologic abnormalities, MR imaging may be helpful in
      distinguishing between the two entities. We report a case in which MR imaging
      helped us to diagnose silent rabies antemortem, which was subsequently confirmed
      at autopsy.

PMID- 11950659
TI  - Reassessment of sphenoid dysplasia associated with neurofibromatosis type 1.
AB  - BACKGROUND AND PURPOSE: Sphenoid dysplasia associated with neurofibromatosis type
      1 is classically thought to be primarily related to abnormal development of the
      sphenoid bone. We investigated the possibility that these changes may be
      progressive. METHODS: We conducted a retrospective review of sphenoid bone
      changes in all patients with craniofacial neurofibromatosis type 1 who had
      undergone CT (31 patients) and MR imaging (seven patients) at our facility. A
      review of repeat images of 20 patients permitted analysis of progressive sphenoid
      bone changes. RESULTS: Eighteen patients had abnormalities of the sphenoid wings,
      13 of whom also had enlargement of the middle cranial fossa compatible with
      descriptions of classic sphenoid dysplasia. All the patients with sphenoid
      dysplasia had neurofibromas in the ipsilateral superficial temporal fossa that
      were often contiguous with a radiologically abnormal temporo-squamosal suture.
      All except one had tumor infiltration in the deep orbit, contiguous with the
      sphenoid wings. Four patients had radiologic evidence of progressive sphenoid
      bone changes over time. CONCLUSION: The origin of sphenoid bone changes may be
      multifactorial. A modified concept of sphenoid dysplasia is proposed that
      emphasizes interaction between neurofibromas and sphenoid bone during skull
      development.

PMID- 11950661
TI  - Orbital Lyme disease: MR imaging before and after treatment: case report.
AB  - Lyme disease is a multi-system organ disease caused by Borrelia burgdorferi.
      Although ocular manifestations have been reported, these remain a rare feature of
      the disease. To our knowledge, the radiology literature has not documented
      orbital Lyme disease both before and after treatment. We present the MR imaging
      findings of florid Lyme disease affecting the extraocular muscles in a 46-year
      old man. A follow-up MR imaging study performed 6 months after a course of
      antibiotic therapy revealed complete resolution of the myositic changes.

PMID- 11950660
TI  - Ferumoxtran-10, a superparamagnetic iron oxide as a magnetic resonance
      enhancement agent for imaging lymph nodes: a phase 2 dose study.
AB  - BACKGROUND AND PURPOSE: Dextran-coated ultrasmall superparamagnetic iron oxide
      ferumoxtran-10 (Combidex) is used in reticuloendothelial MR imaging. Our purpose
      was to determine the optimal dose and imaging time for lymph node evaluation.
      MATERIALS: Twenty-four healthy volunteers underwent neck MR imaging before and 6,
      12, 24, and 36 hours after receiving 1.1, 1.7, 2.6, or 3.4 mg Fe/kg ferumoxtran
      10. Vital signs, serum and urine levels, and adverse events were monitored.
      Qualitative nodal architecture, size, and signal-intensity changes were assessed
      on T1-, T2-, and T2*-weighted (fast field-echo 25 degrees or 80 degrees flip
      angle [FFE-25 or FFE-80]) images. Region-of-interest intensities were measured
      quantitatively. RESULTS: Consistently strong enhancement in normal nodes was
      found with 24- and 36-hour T2- and T2*-weighted imaging after 2.6 and 3.4 mg
      Fe/kg doses. No serious adverse events occurred. With 2.6 mg Fe/kg, unblinded (vs
      blinded) specificities at 24 and 36 hours, respectively, were 100% and 100% (vs
      88% and 88%) with T2-weighted, 96% and 96% (vs 73% and 85%) with FFE-25, and 100%
      and 92% (vs 85% and 88%) with FFE-80 sequences. With 3.4 mg Fe/kg, unblinded (vs
      blinded) specificities at 24 and 36 hours, respectively, were 89% and 79% (vs 75%
      and 75%) with T2-weighted, 84% and 79% (vs 95% and 100%) with FFE-25, and 95% and
      79% (vs 95% and 80%) with FFE-80 sequences. CONCLUSION: Ferumoxtran-10 nodal
      imaging appears to be effective and safe. Signal intensity and specificity for
      normal nodes were best 24 or 36 hours after 2.6 and 3.4 mg Fe/kg doses. Nodal
      conspicuity was best with T2- and T2*-weighted sequences.

PMID- 11950662
TI  - Necrotizing neurosarcoidosis masquerading as a left optic nerve meningioma: case
      report.
AB  - Isolated neurosarcoidosis involving the optic nerve meninges is extremely rare
      and is often indistinguishable from a meningioma in its anatomic site and MR
      imaging presentation. Characteristic findings include enhanced perineural
      encasement and thickening of the affected optic nerve on contrast-enhanced T1
      weighted cranial MR imaging studies. We present the case report of a patient with
      isolated necrotizing neurosarcoidosis of the left optic nerve, with clinical and
      MR imaging findings strongly suggestive of a preoperative diagnosis of a
      meningioma.

PMID- 11950663
TI  - Neurenteric cyst in the cerebellopontine angle with xanthogranulomatous changes:
      serial MR findings with pathologic correlation.
AB  - We report serial MR findings in a middle-aged woman with a neurenteric cyst
      involving the cerebellopontine angle cistern with xanthogranulomatous changes. On
      the initial gadolinium-enhanced T1-weighted MR images, the solid portion of the
      lesion had homogeneously strong enhancement. Follow-up MR images obtained 6
      months later showed that the mass had increased in size; however, the solid
      portion decreased in size. The enhancing solid portion corresponded to the
      xanthogranulomatous changes on pathologic correlation.

PMID- 11950664
TI  - Bimaxillary chondrosarcoma: clinical, radiologic, and histologic correlation.
AB  - In this report, we describe an unusual case of chondrosarcoma that involved the
      entire bimaxillary and nasal skeleton. The pathogenesis, correlation of
      histopathology with radiology, and management of chondrosarcoma are reviewed.

PMID- 11950665
TI  - Nasal teeth: report of three cases.
AB  - The ectopic eruption of the teeth into the nasal cavity is a rare phenomenon. We
      report cases: two involving the nasal cavity and one involving the hard palate
      and complicated by Aspergillus rhinitis. We describe the clinical and radiologic
      presentation of these cases and discuss their etiology, complications, diagnosis,
      and treatment.

PMID- 11950666
TI  - Interaction of vascular smooth muscle cells with collagen-impregnated
      embolization coils studied with a novel quantitative in vitro model.
AB  - BACKGROUND AND PURPOSE: Modifications of aneurysm occlusion devices and other
      biologically active molecules may reduce the risk of recanalization by promoting
      vascular cell migration, adhesion, and proliferation. Our purpose was to apply in
      vitro methods in the qualitative and quantitative analysis of vascular smooth
      muscle cell (VSMC) interactions with collagen-impregnated microcoils. METHODS:
      The adhesion of rat aortic VSMCs to collagen fiber bundles (CFBs), nitinol coils,
      and collagen-impregnated nitinol coils (CINCs) was examined by using an assay
      consisting of monopulse exposure to increasing concentrations of rat aortic
      VSMCs. Exposed devices were washed and examined by using confocal fluorescence
      microscopy. Adhesion coefficients, which quantitatively express the cell-binding
      quality of a surface, were determined by using a mathematical model for cell
      device interactions. RESULTS: VSMCs, attached to devices, spread out and extended
      cytoplasmic projections over the contact surface. Cell distribution was random on
      CFBs and within interloop troughs on nitinol coils. On collagen-impregnated
      coils, VSMCs were selectively concentrated on the collagen between coil loops.
      The average adhesion coefficient was 25.0 for CFBs, 8.5 for CINCs (250-microm
      pitch), and 6.5 for nitinol coils. Adhesion coefficient differences for the three
      devices were significant (P =.044). CONCLUSION: The monopulse exposure assay is a
      simple and reproducible in vitro test that provides qualitative information about
      the morphology and topography of cell-device contacts and permits quantitative
      measurement of the intrinsic cell-binding quality of the test device. VSMCs
      exposed to collagen-impregnated microcoils selectively attach to collagen.
      Collagen enhances the rate of VSMC adhesion to embolic devices, and the degree of
      enhancement correlates with the surface area constituted by collagen.

PMID- 11950667
TI  - Surgical salvage of microcatheter-induced aneurysm perforation during coil
      embolization.
AB  - We report a case of iatrogenic aneurysm rupture during coil embolization in a 55
      year-old woman. Surgical intervention resulted in a good clinical outcome. To our
      knowledge, this technique for the salvage of catheter-induced aneurysm
      perforation has not been previously reported.

PMID- 11950668
TI  - Clinical benefits of rotational 3D angiography in endovascular treatment of
      ruptured cerebral aneurysm.
AB  - BACKGROUND AND PURPOSE: Recent neurointerventional and neurosurgical technologies
      require an understanding of lesions and adjacent structures in three dimensions.
      To clarify the clinical benefits of rotational 3D digital subtraction angiography
      (DSA), we retrospectively analyzed its advantages and disadvantages at the time
      of interventional procedures for ruptured cerebral aneurysms. METHODS: From
      January 1998 through September 2000, 85 patients with a ruptured cerebral
      aneurysm were treated with Guglielmi detachable coils in the acute phase. Data
      for the patients treated before availability of 3D DSA (group A, 52 patients)
      were compared with data for patients treated after availability of 3D DSA (group
      B, 33 patients). Variables analyzed were age, sex, location of aneurysm, size of
      aneurysm, number of implanted coils, number of DSA exposures, and total amount of
      contrast medium used. RESULTS: No statistically significant differences between
      the groups were noted when we compared the age, sex, aneurysm location, aneurysm
      size, and number of implanted coils. The number of DSA exposures was decreased in
      total by using 3D DSA (P <.0001), not only to determine the working projection (P
      <.0001) but also during the procedure (P <.0002). However, no statistically
      significant difference was noted in the comparison of total amount of contrast
      medium. CONCLUSION: Three-dimensional DSA allows acquisition of high-quality 3D
      images of cerebral arteries and also allows observation and analysis from
      multiple directions to determine the appropriate working projection for
      embolization. Three-dimensional DSA is essential for optimal diagnosis and
      embolization of cerebral aneurysms and can reduce the number of exposures.

PMID- 11950669
TI  - Recurrence of dural arteriovenous fistula in another location after selective
      transvenous coil embolization: report of two cases.
AB  - Two cases of a second dural arteriovenous fistula (DAVF), both developing in
      different locations after selective transvenous embolization of the first DAVF,
      are presented. One recurrent DAVF developed on the sigmoid sinus 5 months after
      transvenous embolization of a DAVF in the paratransverse sinus channel, and the
      other recurrence developed around the jugular bulb 5 months after transvenous
      embolization of a cavernous DAVF. The former was obliterated by a second
      embolization, and the latter disappeared spontaneously at 20 months.

PMID- 11950670
TI  - A technique of GDC embolization for deeply bilobulated aneurysms.
AB  - The endovascular occlusion of deeply bilobulated aneurysms is a technical
      challenge. Recently, we successfully treated three patients with deeply
      bilobulated aneurysms by using Guglielmi detachable coils. The embolization
      technique was conventional, but it required several special technical
      considerations. In this report, we describe the technique of coil embolization of
      deeply bilobulated aneurysms.

PMID- 11950671
TI  - Brain abscess after endovascular coiling of a saccular aneurysm: case report.
AB  - CNS infection occurring after therapeutic angiography is rare. We present a case
      report of a brain abscess complicating endovascular coiling of an intracranial
      aneurysm. We recommend the use of prophylactic antibiotics, especially when
      performing therapeutic CNS angiography.

PMID- 11950672
TI  - Use of ICD-9 coding for estimating the occurrence of cerebrovascular
      malformations.
AB  - BACKGROUND AND PURPOSE: Accurate epidemiologic data concerning cerebrovascular
      malformations are scarce. Our goals were to determine the distribution of lesions
      in the International Classification of Diseases, Ninth Revision, (ICD-9) code for
      cerebrovascular malformations and to evaluate the use of state discharge
      registries for estimating their detection rate. METHODS: We reviewed records of
      all patients discharged from our center between January 1, 1992, and June 30,
      1999, whose diagnoses included the ICD-9 code for cerebrovascular anomaly (code
      747.81) to determine the accuracy of the coding. Hospital admission rates for
      cerebrovascular anomaly were calculated by using the 1995-1999 state discharge
      databases of California and New York. RESULTS: Of 804 patients with this code,
      706 (88%) had a lesion consistent with the diagnosis. Five lesions accounted for
      99% of the diagnoses; the two most common were AVM (66%) and cavernous
      malformation (13%). The ratio of AVMs to all cerebrovascular anomalies was
      similar to that in a prior population-based study. The sensitivity of identifying
      a patient with cerebrovascular malformation by using ICD-9 coding was 94%; the
      false-positive rate was 1.7 cases per 100,000 person-years. For California and
      New York, rates of first hospital admission for cerebrovascular malformation were
      1.5 and 1.8 cases per 100,000 person-years, respectively. CONCLUSION: Rates of
      admission for cerebrovascular malformations calculated from state discharge
      databases are consistent with disease detection rates in the range of 1 case per
      100,000 person-years. However, the false-positive rate for coding is in the same
      range as the disease detection rate. Thus, current state discharge registries
      cannot serve as sources of detailed epidemiologic data.

PMID- 11950674
TI  - 3.3F catheter/sheath system for use in diagnostic neuroangiography.
AB  - BACKGROUND AND PURPOSE: Although neuroangiography remains the criterion standard
      standard for the detection of and surgical/interventional planning for
      cerebrovascular diseases, it usually requires that patients be confined to bed
      rest for several hours after angiography to prevent local complications.
      Decreasing catheter size has reduced the risk of hemorrhagic complications
      associated with early ambulation after angiography. For this study, we
      prospectively evaluated the clinical feasibility of a 3.3F catheter/sheath system
      for selective neuroangiography. METHODS: One hundred seventeen consecutive
      patients (49 men, 68 women; age range, 18-83 years; mean age, 56.9 years)
      underwent selective neuroangiography using 3.3F catheters. The exclusion criteria
      for this study included a subsequent surgical/neurointerventional procedure
      performed within 18 hours and necessity of arch aortography, which is routinely
      performed for the first examination of patients with ischemic cerebrovascular
      diseases. The procedure was evaluated prospectively in terms of success rate,
      compression time of the arterial puncture site, and periprocedural complications.
      RESULTS: Selective catheterization of the intended arteries was performed in 99%
      of the carotid arteries and 97.4% of the vertebral arteries. No neurologic
      complications or local hemorrhagic complications were observed. Manual
      compression time after the procedure ranged from 3 to 7 minutes (mean, 3.7
      minutes), and patient bed rest after the procedure ranged from 2 to 3 hours
      (mean, 2.04 hours). CONCLUSION: Selective neuroangiography with a 3.3F
      catheter/sheath system is feasible and enables early ambulation in selected
      patients.

PMID- 11950673
TI  - Study of the patency of small arterial branches after stent placement with an
      experimental in vivo model.
AB  - BACKGROUND AND PURPOSE: The patency of intracranial perforating arteries after
      stent placement is unknown despite the general clinical use of intracranial
      arterial stenting. METHODS: We deployed stainless steel stents in the abdominal
      aorta across the lumbar artery in eight normal rabbits in which the diameters of
      the abdominal arterial vessels were similar to those of human intracranial
      arteries. We evaluated the patency via angiographic and scanning electron
      microscopic methods 3 months after stent placement. Histopathologic evaluation
      was also performed for one rabbit. RESULTS: The lumbar arteries were patent, even
      when stent struts crossed the ostium, except in one rabbit in which intimal
      dissection occurred intraoperatively. The scanning electron microscopy showed
      that the regenerative endothelium had grown onto the strut at the ostium of the
      lumbar artery. CONCLUSION: We confirmed the patency of the lumbar arteries in
      this study by using normal rabbits. Thus, intracranial stenting may not pose a
      risk of occluding perforating arteries of the same diameter of the lumbar artery,
      even if stent struts cover the ostium.

PMID- 11950676
TI  - Investigations into the association between cervicomedullary neuroschisis and
      mirror movements in patients with Klippel-Feil syndrome.
AB  - BACKGROUND AND PURPOSE: Our purpose was to investigate the association between
      cervicomedullary neuroschisis and mirror movements in patients with Klippel-Feil
      syndrome (KFS). METHODS: We conducted a retrospective analysis of 23 patients
      with KFS who were seen at our institution during a 10-year period. Sixteen of the
      23 patients had undergone adequate axial view cross-sectional imaging of the
      upper cervical spine. The degree of neuroschisis was assessed for each patient,
      using an objective scoring system. Twelve patients were evaluated for the
      presence or absence of mirror movements. RESULTS: A high percentage of female
      patients with KFS was noted (17 [74%] of 23 patients). Adequate cross-sectional
      images were available for 16 of the 23 patients, six (38%) of whom had some form
      of cervicomedullary neuroschisis. Five of the six patients had been clinically
      evaluated, and all were shown to have mirror movements. One patient with Chiari
      II malformation, which obscured evaluation for neuroschisis, also had mirror
      movements. Of the remaining nine patients without cervicomedullary neuroschisis,
      six were evaluated, and none of the six had mirror movements. A review of the
      theoretical neuroanatomic basis of mirror movements is presented herein, and
      neurosurgical management concerns for patients with KFS are discussed.
      CONCLUSION: A strong association exists between cervicomedullary neuroschisis and
      mirror movements in cases of KFS. Screening of patients with mirror movements may
      help identify clinically unsuspected KFS and may also help stratify risk within
      this patient population, identifying patients who might benefit from early
      neurosurgical intervention.

PMID- 11950675
TI  - Value of MR imaging of the brain in children with hypoxic coma.
AB  - BACKGROUND AND PURPOSE: The contribution of MR imaging to identify hypoxic
      ischemic injuries has been studied mostly in neonates or adults. The purpose of
      this study was to describe the MR imaging findings of toddlers and older children
      with hypoxic coma and to analyze the prognostic value of an MR imaging scoring
      system. METHODS: The conditions of 40 children with hypoxic coma (age range, 6
      weeks to 18 years) were clinically graded according to the pediatric risk of
      mortality score, and MR imaging studies were performed. Sixty-four MR imaging
      studies were distributed in five categories according to their timing relative to
      the hypoxic event: days 1 through 3, 4-7, 8-15, 16-50, and after day 50. These
      were evaluated retrospectively by using an eight-point scoring system based on
      two lesion categories assessing watershed areas and basal ganglia involvement,
      including signal intensity and morphologic features with respect to maturation
      related norms. Two age groups (< or =1 year and >1 year) were considered. The
      surviving children were grouped according to neurologic outcome. RESULTS: The
      occurrence of watershed areas or basal ganglia involvement was not significantly
      different in association with age. Sixteen children died. Twelve children had
      moderate to severe sequelae resulting from neurodevelopmental disabilities, and
      12 had good neurologic outcomes. There was no correlation between pediatric risk
      of mortality score and neurologic evolution. There was a strong correlation
      between first MR imaging score (P <.001) and neurologic outcome. The sensitivity
      of the first MR imaging score was high (96%), even when obtained during the first
      3 days, with a specificity of 50% and a positive predictive value of 82%. Six
      patients with definite abnormal MR imaging findings experienced good neurologic
      outcomes. CONCLUSION: The MR imaging scoring system proposed in this study can be
      used to establish an early prognosis in a significant proportion of children with
      hypoxic coma. It is helpful, even during the first 3 days after the event.
      However, some patients with definite abnormal MR imaging findings may experience
      good neurologic evolution.

PMID- 11950677
TI  - Multiple pericallosal lipomas in two siblings with frontonasal dysplasia.
AB  - We report cases of two siblings with frontonasal dysplasia (FND) associated with
      multiple pericallosal lipomas in almost similar locations. In each sibling two
      separate curvilinear pericallosal lipomas were present-one in relation to the
      posterior part of the corpus callosum and the other in relation to the rostrum.
      To our knowledge, multiple pericallosal lipomas in association with FND have not
      been described before. Pericallosal lipomas in cases of FND are of the
      tubulonodular type; they have been reported only in relation to the anterior part
      of the corpus callosum.

PMID- 11950678
TI  - In Re: Belliveau JW, Kennedy DN, McKinstry C, et al. Functional mapping of the
      human visual cortex by magnetic resonance imaging. Science 1991 Nov
      1;254(5032):716-719.

PMID- 11950680
TI  - Management of aneurysm perforation during Guglielmi electrodetachable coil
      placement.

PMID- 11950681
TI  - MR imaging in comatose survivors of cardiac resuscitation.

PMID- 11950682
TI  - The petrosquamosal venous channel.

PMID- 11950683
TI  - In re: arterial dissection complicating cerebral angiography and cerebrovascular
      interventions.

PMID- 11950684
TI  - The B cell: a good guy in vascular disease?

PMID- 11950685
TI  - When sleeping beauty turns ugly: mitochondria in hypoxia.

PMID- 11950686
TI  - Pleiotropic effects of chemokines in vascular lesion development.

PMID- 11950687
TI  - Factor V and thrombotic disease: description of a janus-faced protein.
AB  - The generation of thrombin by the prothrombinase complex constitutes an essential
      step in hemostasis, with thrombin being crucial for the amplification of blood
      coagulation, fibrin formation, and platelet activation. In the prothrombinase
      complex, the activated form of coagulation factor V (FVa) is an essential
      cofactor to the enzyme-activated factor X (FXa), FXa being virtually ineffective
      in the absence of its cofactor. Besides its procoagulant potential, intact factor
      V (FV) has an anticoagulant cofactor capacity functioning in synergy with protein
      S and activated protein C (APC) in APC-catalyzed inactivation of the activated
      form of factor VIII. The expression of anticoagulant cofactor function of FV is
      dependent on APC-mediated proteolysis of intact FV. Thus, FV has the potential to
      function in procoagulant and anticoagulant pathways, with its functional
      properties being modulated by proteolysis exerted by procoagulant and
      anticoagulant enzymes. The procoagulant enzymes factor Xa and thrombin are both
      able to activate circulating FV to FVa. The activity of FVa is, in turn,
      regulated by APC together with its cofactor protein S. In fact, the regulation of
      thrombin formation proceeds primarily through the upregulation and downregulation
      of FVa cofactor activity, and failure to control FVa activity may result in
      either bleeding or thrombotic complications. A prime example is APC resistance,
      which is the most common genetic risk factor for thrombosis. It is caused by a
      single point mutation in the FV gene (factor V(Leiden)) that not only renders FVa
      less susceptible to the proteolytic inactivation by APC but also impairs the
      anticoagulant properties of FV. This review gives a description of the dualistic
      character of FV and describes the gene-gene and gene-environment interactions
      that are important for the involvement of FV in the etiology of venous
      thromboembolism.

PMID- 11950688
TI  - Regulation of functions of vascular wall cells by tissue factor pathway
      inhibitor: basic and clinical aspects.
AB  - Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that
      inhibits the initial reactions of blood coagulation. A major pool of TFPI is the
      form associated with the surface of endothelial cells, which is speculated to
      play an important role in regulating the functions of vascular wall cells. TFPI
      consists of 3 tandem Kunitz inhibitor domains, the first and second of which
      inhibit the tissue factor-factor VIIa complex and factor Xa, respectively. Recent
      findings indicate that TFPI has another function, ie, the modulation of cell
      proliferation. This function is based on the interaction of the C-terminal region
      of TFPI with these cells. In addition to endothelial cells, it has been shown
      that many other vascular wall cells can synthesize TFPI, eg, mesangial cells,
      smooth muscle cells, monocytes, fibroblasts, and cardiomyocytes. TFPI is
      associated with these cells mainly through heparan sulfate proteoglycans on their
      surface. However, recent findings suggest that there are several other candidates
      for TFPI-binding proteins on these cells. On the other hand, studies on plasma
      levels of TFPI in patients with various diseases suggest that TFPI may be a
      marker of endothelial cell dysfunction. An increasing number of reports suggest
      that recombinant TFPI may attenuate thrombosis and prevent restenosis. Clinical
      trials are needed to explore these possibilities. Recent reports also indicate
      that the application of recombinant TFPI or TFPI gene transfer prevents
      restenosis in addition to thrombosis after arterial injury in the animal model;
      corroboration of these reports awaits clinical investigation.

PMID- 11950689
TI  - RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and
      vascular function.
AB  - In 1997, investigators isolated a secreted glycoprotein that blocked osteoclast
      differentiation from precursor cells, prevented osteoporosis (decreased bone
      mass) when administered to ovariectomized rats, and resulted in osteopetrosis
      (increased bone mass) when overexpressed in transgenic mice. Since then, the
      isolation and characterization of the protein named osteoprotegerin (OPG) has
      stimulated much work in the fields of endocrinology, rheumatology, and
      immunology. OPG functions as a soluble decoy receptor for receptor activator of
      nuclear factor-kappaB ligand (RANKL, or OPG ligand) and shares homologies with
      other members of the tumor necrosis factor receptor superfamily. OPG acts by
      competing with the receptor activator of nuclear factor-kappaB, which is
      expressed on osteoclasts and dendritic cells for specifically binding to RANKL.
      RANKL is crucially involved in osteoclast functions and bone remodeling as well
      as immune cell cross-talks, dendritic cell survival, and lymph node
      organogenesis. More recently, emerging evidence from in vitro studies and mouse
      genetics attributed OPG an important role in vascular biology. In fact, OPG could
      represent the long sought-after molecular link between arterial calcification and
      bone resorption, which underlies the clinical coincidence of vascular disease and
      osteoporosis, which are most prevalent in postmenopausal women and elderly
      people.

PMID- 11950690
TI  - CCR2 deficiency decreases intimal hyperplasia after arterial injury.
AB  - Monocyte chemoattractant protein (MCP)-1 is upregulated in atherosclerotic
      plaques and in the media and intima of injured arteries. CC chemokine receptor 2
      (CCR2) is the only known functional receptor for MCP-1. Mice deficient in MCP-1
      or CCR2 have marked reductions in atherosclerosis. This study examines the effect
      of CCR2 deficiency in a murine model of femoral arterial injury. Four weeks after
      injury, arteries from CCR2(-/-) mice showed a 61.4% reduction (P<0.01) in intimal
      area and a 62% reduction (P<0.05) in intima/media ratio when compared with
      CCR2(+/+) littermates. The response of CCR2(+/-) mice was not significantly
      different from that of CCR2(+/+) mice. Five days after injury, the medial
      proliferation index, determined by bromodeoxyuridine incorporation, was decreased
      by 59.8% in CCR2(-/-) mice when compared with CCR2(+/+) littermates (P<0.05).
      Although leukocytes rapidly adhered to the injured arterial surface, there was no
      significant macrophage infiltration in the arterial wall of either CCR2(-/-) or
      CCR2(+/+) mice 5 and 28 days after injury. These results demonstrate that CCR2
      plays an important role in mediating smooth muscle cell proliferation and intimal
      hyperplasia in a non-hyperlipidemic model of acute arterial injury. CCR2 may thus
      be an important target for inhibiting the response to acute arterial injury.

PMID- 11950691
TI  - Oxidative stress in human abdominal aortic aneurysms: a potential mediator of
      aneurysmal remodeling.
AB  - Abdominal aortic aneurysm (AAA) is an inflammatory disorder characterized by
      localized connective tissue degradation and smooth muscle cell (SMC) apoptosis,
      leading to aortic dilatation and rupture. Reactive oxygen species are abundantly
      produced during inflammatory processes and can stimulate connective tissue
      degrading proteases and apoptosis of SMCs. We hypothesized that reactive oxygen
      species are locally increased in AAA and lead to enhanced oxidative stress. In
      aortas from patients undergoing surgical repair, superoxide levels (measured by
      lucigenin-enhanced chemiluminescence) were 2.5-fold higher in the AAA segments
      compared with the adjacent nonaneurysmal aortic (NA) segments (6638+/-2164 versus
      2675+/-1027 relative light units for 5 minutes per millimeter squared,
      respectively; n=7). Formation of thiobarbituric acid-reactive substances and
      conjugated dienes, 2 indices of lipid peroxidation, were increased 3-fold in AAA
      compared with NA segments. Immunostaining for nitrotyrosine was significantly
      greater in AAA tissue. Dihydroethidium staining indicated that increased
      superoxide in AAA segments was localized to infiltrating inflammatory cells and
      to SMCs. Expression of the NADPH oxidase subunits p47(phox) and p22(phox) and
      NAD(P)H oxidase activity were increased in AAA segments compared with NA
      segments. Thus, oxidative stress is markedly increased in AAA, in part through
      the activation of NAD(P)H oxidase, and may contribute to the disease
      pathogenesis.

PMID- 11950692
TI  - Role of mitochondrial oxidant generation in endothelial cell responses to
      hypoxia.
AB  - Endothelial cells increase their secretion of the cytokine interleukin-6 (IL-6)
      during hypoxia, which then acts in an autocrine fashion to increase the
      permeability of cell monolayers. These responses are attenuated by antioxidants,
      suggesting that reactive oxygen species (ROS) participate in signaling in hypoxic
      endothelium. We tested whether mitochondria are responsible for these ROS in
      human umbilical vein endothelial cells exposed to hypoxia. Oxidation of the probe
      2', 7'-dichlorodihydrofluorescein to fluorescent dichlorofluorescein or the probe
      dihydroethidium was used to assess oxidant signaling, whereas permeability was
      assessed by using transendothelial electrical resistance. Hypoxia elicited
      increases in dichlorofluorescein and dihydroethidium fluorescence that were
      abrogated by the mitochondrial electron transport (ET) inhibitors rotenone (2
      micromol/L) and diphenyleneiodonium (5 micromol/L). The same ET inhibitors also
      attenuated hypoxia-induced increases in nuclear factor-kappaB (NF-kappaB)
      activation, although they did not abrogate NF-kappaB activation in response to
      endotoxin (lipopolysaccharide). ET inhibition also abolished the hypoxia-induced
      increases in IL-6 mRNA expression, hypoxia-stimulated IL-6 secretion into the
      media, and the hypoxia-induced increases in transendothelial electrical
      resistance of human umbilical vein endothelial cell monolayers. By contrast, the
      above responses to hypoxia were not significantly affected by treatment with the
      NAD(P)H oxidase inhibitor apocynin (30 micromol/L), the xanthine oxidase
      inhibitor allopurinol (100 micromol/L), or the NO synthase inhibitor N-nitro-L
      arginine (100 micromol/L). We conclude that ROS signals originating from the
      mitochondrial ET chain trigger the increase in NF-kappaB activation, the
      transcriptional activation of IL-6, the secretion of IL-6 into the cell culture
      media, and the increases in endothelial permeability observed during hypoxia.

PMID- 11950693
TI  - Vitamin C protects against hypochlorous Acid-induced glutathione depletion and
      DNA base and protein damage in human vascular smooth muscle cells.
AB  - Hypochlorous acid (HOCl), generated by myeloperoxidase released from activated
      macrophages, is thought to contribute to vascular dysfunction and oxidation of
      low density lipoproteins (LDLs) in atherogenesis. We have previously shown that
      HOCl exposure can cause chlorination and oxidation of isolated DNA and that
      vitamin C protects human arterial smooth muscle cells against oxidized LDL
      mediated damage. We report in the present study that vitamin C attenuates HOCl
      induced DNA base and protein damage and depletion of intracellular glutathione
      (GSH) and ATP in human arterial smooth muscle cells. Cells were pretreated in the
      absence or presence of 100 micromol/L vitamin C (24 hours) and then exposed to
      HOCl (0 to 500 micromol/L, 0 to 60 minutes) in the absence of vitamin C.
      Intracellular GSH and ATP levels were depleted by HOCl treatment, and gas
      chromatography-mass spectroscopy revealed a concentration- and time-dependent
      increase in DNA base oxidation and protein damage (measured as 3-chlorotyrosine).
      Pretreatment of smooth muscle cells with vitamin C significantly reduced the
      extent of HOCl-induced DNA and protein damage and attenuated decreases in
      intracellular ATP and GSH. Our findings suggest that physiological levels of
      vitamin C provide an important antioxidant defense against HOCl-mediated injury
      in atherosclerosis.

PMID- 11950694
TI  - Oxidized cholesteryl linoleates stimulate endothelial cells to bind monocytes via
      the extracellular signal-regulated kinase 1/2 pathway.
AB  - Oxidation products of cholesteryl esters have been shown to be present in
      oxidized low density lipoprotein and in atherosclerotic lesions. Monocyte
      adhesion to the endothelium is an initiating crucial event in atherogenesis.
      Here, we show that in vitro oxidized cholesteryl linoleate (oxCL) stimulated
      human umbilical vein endothelial cells (HUVECs) to bind human peripheral blood
      mononuclear cells as well as monocyte-like U937 cells but not peripheral blood
      neutrophils or neutrophil-like HL-60 cells. Among the oxidation products
      contained in oxCLs, 9-oxononanoyl cholesterol (9-ONC) and cholesteryl linoleate
      hydroperoxides stimulated U937 cell adhesion. OxCL-induced U937 cell adhesion was
      inhibited by an antibody against the connecting segment-1 region of fibronectin.
      Neither oxCL nor 9-ONC induced activation of the classical nuclear factor-kappaB
      pathway. In contrast, stimulation of HUVECs with oxCL resulted in phosphorylation
      of the extracellular signal-regulated kinase 1/2. Moreover, U937 cell adhesion
      induced by 9-ONC and oxCL was blocked by a mitogen-activated protein
      kinase/extracellular signal-regulated kinase inhibitor and a protein kinase C
      inhibitor. Taken together, oxCLs stimulate HUVECs to specifically bind monocytes,
      involving endothelial connecting segment-1 and the activation of a protein kinase
      C- and mitogen-activated protein kinase-dependent pathway. Thus, oxidized
      cholesteryl esters may play an important role as novel mediators in the
      initiation and progression of atherosclerosis.

PMID- 11950695
TI  - Homocysteine upregulates vascular cell adhesion molecule-1 expression in cultured
      human aortic endothelial cells and enhances monocyte adhesion.
AB  - Elevated plasma homocysteine is an independent risk factor for atherosclerosis.
      We hypothesized that homocysteine enhances monocyte/human aortic endothelial cell
      (HAEC) interactions, a pivotal early event in atherogenesis, by upregulating
      endothelial adhesion molecules. After incubation of cultured HAECs with reduced
      DL-homocysteine for up to 24 hours, adhesion of human monocytes to homocysteine
      stimulated HAECs was significantly upregulated in a time- and dose-dependent
      fashion. Pretreatment of HAECs with 100 micromol/L homocysteine caused a 4.5-fold
      increase in the adhesion of normal human monocytes (P<0.001). Similarly, adhesion
      of monocytic U937 cells was maximally elevated by 3.5-fold at 100 micromol/L
      homocysteine (P<0.001). In support of our hypothesis, vascular cell adhesion
      molecule (VCAM)-1 mRNA expression increased 5-fold in HAECs after 3 hours of
      treatment with 100 micromol/L homocysteine, as assessed by quantitative reverse
      transcription- polymerase chain reaction. Neutralizing antibody studies confirmed
      the involvement of VCAM-1 in mediating monocyte adhesion to homocysteine
      stimulated HAECs. Coincubation of HAECs with homocysteine and tumor necrosis
      factor-alpha synergistically elevated monocyte adhesion as well as VCAM-1 protein
      expression, with the latter evaluated by flow cytometry. Preincubation of HAECs
      with cyclooxygenase inhibitors completely abrogated homocysteine-induced monocyte
      adhesion, whereas scavenging reactive oxygen species and the elevation of NO
      caused partial inhibition only. These data support the notion that the
      proinflammatory effects of homocysteine may have important implications in
      atherogenesis.

PMID- 11950696
TI  - C-reactive protein and soluble vascular cell adhesion molecule-1 are associated
      with elevated urinary albumin excretion but do not explain its link with
      cardiovascular risk.
AB  - An elevated urinary albumin excretion rate (UAER) is associated with an increased
      risk of cardiovascular mortality, but the pathophysiological mechanism underlying
      this association is poorly understood. To investigate the role of endothelial
      dysfunction, leukocyte adhesion, and low-grade inflammation (1) in the
      development of elevated UAER (study I) and (2) in linking elevated UAER with risk
      of cardiovascular mortality (study II), we performed a prospective study in an
      age-, sex-, and glucose tolerance- stratified sample of a population-based cohort
      aged 50 to 75 years. High levels of von Willebrand factor, soluble vascular cell
      adhesion molecule-1 (sVCAM-1), and C-reactive protein (CRP) were used as markers
      of endothelial dysfunction, leukocyte adhesion, and low-grade inflammation,
      respectively. For study I, subjects who had normal UAER at baseline (n=316
      subjects, 66 with type 2 diabetes) were reexamined after a mean follow-up of 6.1
      years. The development of elevated UAER was defined as a mean albumin-to
      creatinine ratio >2.0 mg/mmol at follow-up. Age-, sex-, and glucose tolerance-
      adjusted logistic regression analyses showed the development of elevated UAER to
      be significantly associated with levels of sVCAM-1 and CRP (odds ratio 1.14 [95%
      CI 1.02 to 1.27] per 10% increase of sVCAM-1 and odds ratio 1.17 [95% CI 1.04 to
      1.32] per 50% increase of CRP). The results were not materially different after
      additional adjustment for hypertension, body mass index, cardiovascular disease,
      and creatinine clearance or stratification by the presence of diabetes. For study
      II, the vital status of all subjects (n= 575) was determined after a mean follow
      up of 6.6 years. Eighty-one of 575 subjects died (30 died of cardiovascular
      disease). The presence of elevated UAER at baseline was associated with a 4.1
      fold (1.94 to 8.73) increased risk of cardiovascular death after adjustment for
      age, sex, and glucose tolerance status. Adjustment for levels of von Willebrand
      factor, sVCAM-1, or CRP did not materially affect the results, nor did additional
      adjustment for the presence of hypertension, retinopathy, and cardiovascular
      disease and for levels of homocysteine, triglycerides, and high density
      lipoprotein cholesterol. Leukocyte adhesion (sVCAM-1) and low-grade inflammation
      (CRP) are determinants of the development of elevated UAER. However, these
      determinants do not explain the association between elevated UAER and
      cardiovascular mortality.

PMID- 11950697
TI  - Interleukin-6 -174G>C polymorphism and risk of coronary heart disease in West of
      Scotland coronary prevention study (WOSCOPS).
AB  - Interleukin (IL)-6 plays an important role in the pathogenesis of coronary heart
      disease (CHD). Two functional polymorphisms in the IL-6 promoter have been
      identified (-174G>C and -572G>C), with both the rare alleles being associated
      with higher plasma levels of IL-6 after bypass surgery and one of them (-174G>C)
      associated with CHD risk. We have studied the contribution of these polymorphisms
      to CHD risk in the West of Scotland Coronary Prevention Study (WOSCOPS), a
      primary prevention trial that demonstrated the effectiveness of pravastatin in
      reducing morbidity and mortality from CHD. Four hundred ninety-eight cases
      (consisting of individuals experiencing a cardiovascular event during 4.8 years
      of follow-up) and 1109 controls (individuals matched for age and smoking habits)
      were genotyped. In the placebo group, there was no significant evidence of higher
      risk associated with the -174CC genotype compared with the GG+GC group. However,
      in the pravastatin-treated group, CC homozygotes had a significantly lower risk
      of CHD compared with the GG+GC placebo group (odds ratio 0.46, 95% CI 0.27 to
      0.79), and this remained statistically significant after adjustment for classic
      risk factors. Compared with the GG+GC group, men with the CC genotype had
      modestly, but not significantly, higher baseline levels of IL-6, C-reactive
      protein, or fibrinogen but showed a significantly greater fall in LDL cholesterol
      with statin treatment (P=0.036). The -572G>C polymorphism was not significantly
      associated with any plasma trait or CHD risk. Thus, in subjects under pravastatin
      treatment, the -174CC genotype was associated with a lower risk of CHD. These
      results demonstrate the importance of the inflammatory system in determining the
      risk of CHD and support the nonlipid effect of statins on risk.

PMID- 11950698
TI  - T-786C polymorphism in endothelial NO synthase gene affects cerebral circulation
      in smokers: possible gene-environmental interaction.
AB  - Effects of smoking on white matter lesions, such as lacunar infarction and
      leukoaraiosis, are still controversial. We hypothesized that the endothelial NO
      synthase (eNOS) genotype was a modulating factor for the effect of smoking on
      cerebral circulation. We took a cross-sectional population from the participants
      of a health examination to study the effects of smoking and a single-nucleotide
      polymorphism in the eNOS gene, T-786C. Smokers and nonsmokers were defined as
      having a smoking index (cigarettes per day times years) of >/=200 and 0,
      respectively. One hundred sixty-six male nonsmokers and 344 male smokers were
      recruited. Cerebral blood flow was measured by the (133)Xe inhalation method.
      Genotyping of T-786C was performed by using a newly developed allele-specific
      polymerase chain reaction. Smokers were exposed to greater oxidative stress, as
      estimated by urinary F(2)-isoprostane excretion. In smokers, CC homozygotes of T
      786C showed a significant decrease of cerebral blood flow (56.6+/-13.3, 57.6+/
      11.5, and 44.0+/-7.2 mL/min per 100 g tissue for TT, TC, and CC, respectively;
      P=0.03 by ANOVA) and a significant increase of cerebrovascular resistance,
      whereas the eNOS genotype did not affect these parameters in nonsmokers. This
      result indicated that the eNOS genotype could modify cerebrovascular circulation
      in a general population by potentiating the adverse effect of smoking.

PMID- 11950699
TI  - Quantification of mRNA for endothelial NO synthase in mouse blood vessels by real
      time polymerase chain reaction.
AB  - The mouse is useful in studies of vascular biology because of its well-defined
      genetics and because the mouse genome can be manipulated. However, because only
      small amounts of mRNA can be extracted from blood vessels, the quantification of
      gene expression in individual mice is difficult. Endothelial NO synthase (eNOS)
      plays a major role in the regulation of vascular tone and growth. In addition,
      there appear to be sex differences in the production of NO under basal conditions
      in mouse aortas. The goals of this study were to develop a real-time polymerase
      chain reaction (PCR) method to quantify eNOS mRNA in blood vessels from mice and
      to examine eNOS mRNA levels in vessels from male and female mice. Blood vessels
      were isolated from C57BL/6 mice. Total RNA from individual mice was isolated and
      reverse-transcribed. The number of molecules of eNOS mRNA (after reverse
      transcription) was determined against cDNA standards, with 18S rRNA used as a
      control for RNA input and reverse-transcription efficiency. When expressed as
      copy numbers per nanogram of total RNA or as the ratio of eNOS to 18S rRNA, eNOS
      mRNA was lower in the aortas of female mice than in those of male mice at 7 to 9
      months of age. In contrast, no difference in eNOS mRNA was found in the aortas of
      2-month-old mice. In addition, eNOS mRNA levels were similar in the carotid,
      cerebral, and coronary arteries. These findings provide the first quantitative
      measurements of eNOS mRNA by using real-time PCR in the vessels of mice and
      suggest age- and sex-related differences in the basal levels of eNOS mRNA in
      mice. In addition, the eNOS region that was used for real-time PCR was amplified
      and sequenced for monkeys and other species. With modifications, this region may
      be used to design real-time PCR for eNOS in other species.

PMID- 11950700
TI  - Vascular endothelial growth factor induces SHC association with vascular
      endothelial cadherin: a potential feedback mechanism to control vascular
      endothelial growth factor receptor-2 signaling.
AB  - Vascular endothelial (VE)-cadherin is endothelium specific, mediates homophilic
      adhesion, and is clustered at intercellular junctions. VE-cadherin is required
      for normal development of the vasculature in the embryo and for angiogenesis in
      the adult. Here, we report that VE-cadherin is associated with VE growth factor
      (VEGF) receptor-2 (VEGFR-2) on the exposure of endothelial cells to VEGF. The
      binding parallels receptor phosphorylation on tyrosine residues, which is maximal
      at 5 minutes and then declines within 30 minutes. Tyrosine phosphorylation of VE
      cadherin was maximal at 30 minutes after the addition of the growth factor. At
      this time point, the protein could be coimmunoprecipitated with the adaptor
      protein Shc. Pull-down experiments with different Shc domains and mutants of the
      VE-cadherin cytoplasmic tail have shown that Shc binds to the carboxy-terminal
      domain of the VE-cadherin tail through its Src homology 2 domain (SH2). We found
      that Shc phosphorylation lasts longer in endothelial cells carrying a targeted
      null mutation in the VE-cadherin gene than in VE-cadherin-positive cells. These
      data suggest that VE-cadherin expression exerts a negative effect on Shc
      phosphorylation by VEGFR-2. We speculate that VE-cadherin binding to Shc promotes
      its dephosphorylation through associated phosphatases.

PMID- 11950701
TI  - Cerivastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme a reductase,
      inhibits endothelial cell proliferation induced by angiogenic factors in vitro
      and angiogenesis in in vivo models.
AB  - Cerivastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
      It inhibits the biosynthesis of cholesterol and its precursors: farnesyl
      pyrophosphate and geranylgeranyl pyrophosphate (GGPP), which are involved in Ras
      and RhoA cell signaling, respectively. Statins induce greater protection against
      vascular risk than that expected by cholesterol reduction. Therefore,
      cerivastatin could protect plaque against rupture, an important cause of ischemic
      events. In this study, the effect of cerivastatin was tested on angiogenesis
      because it participates in plaque progression and plaque destabilization.
      Cerivastatin inhibits in vitro the microvascular endothelial cell proliferation
      induced by growth factors, whereas it has no effect on unstimulated cells. This
      growth arrest occurs at the G(1)/S phase and is related to the increase of the
      cyclin-dependent kinase inhibitor p21(Waf1/Cip1). These effects are reversed by
      GGPP, suggesting that the inhibitory effect of cerivastatin is related to RhoA
      inactivation. This mechanism was confirmed by RhoA delocalization from cell
      membrane to cytoplasm and actin fiber depolymerization, which are also prevented
      by GGPP. It was also shown that RhoA-dependent inhibition of cell proliferation
      is mediated by the inhibition of focal adhesion kinase and Akt activations.
      Moreover, cerivastatin inhibits in vivo angiogenesis in matrigel and chick
      chorioallantoic membrane models. These results demonstrate the antiangiogenic
      activity of statins and suggest that it may contribute to their therapeutic
      benefits in the progression and acute manifestations of atherosclerosis.

PMID- 11950702
TI  - Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in
      macrophages.
AB  - The ATP-binding cassette transporter A1 (ABCA1) encodes a membrane protein that
      promotes cholesterol and phospholipid efflux from cells. Mutations in ABCA1 lead
      to HDL deficiency and tissue accumulation of macrophages in patients with
      homozygous Tangier disease. In this study, we examined whether the complete
      absence of ABCA1 or selected inactivation in macrophages is accompanied by an
      increase in atherosclerotic lesion progression in hypercholesterolemic
      apolipoprotein E-deficient (apoE(-/-)) mice and LDLR receptor-deficient (LDLr(-/
      )) mice. The absence of ABCA1 led to reduced plasma cholesterol levels in both
      the apoE(-/-) and LDLr(-/-) mice, along with severe skin xanthomatosis
      characterized by marked foamy macrophages and cholesterol ester accumulation.
      However, the complete absence of ABCA1 did not affect the development,
      progression, or composition of atherosclerotic lesions in either the LDLr(-/-) or
      the apoE(-/-) mice fed a chow or atherogenic diet. In contrast, bone marrow
      transplantation studies demonstrated that the selective inactivation of ABCA1 in
      macrophages markedly increased atherosclerosis and foam cell accumulation in
      apoE(-/-). Taken together, these findings demonstrate that the complete absence
      of ABCA1 has a major impact on plasma lipoprotein homeostasis, and the proposed
      antiatherogenic effect resulting from ABCA1 deficiency is compensated by a less
      atherogenic profile. ABCA1 deficiency in macrophages, however, demonstrates the
      antiatherogenic properties of ABCA1 independent of plasma lipids and HDL levels.

PMID- 11950703
TI  - Opposite effects of plasma from human apolipoprotein A-II transgenic mice on
      cholesterol efflux from J774 macrophages and Fu5AH hepatoma cells.
AB  - Overexpression of human apolipoprotein A-II (hapo A-II) in transgenic mice
      (hAIItg mice) induced marked hypertriglyceridemia and low levels of plasma high
      density lipoprotein (HDL) with a high hapo A-II content. We sought to determine
      whether cholesterol efflux to plasma and HDL from these mice would be affected.
      In the Fu5AH cell system, plasma from hAIItg mice induced a markedly lower
      cholesterol efflux than did control plasma, in accordance with the dependence of
      efflux on HDL concentration. Moreover, HDLs from hAIItg mice were less effective
      acceptors than were control HDLs. In the J774 macrophage cell system,
      pretreatment with cAMP, which upregulates ATP binding cassette transporter 1,
      induced a marked increase in the efflux to hAIItg plasma as well as to purified
      hapo A-I and hapo A-II, whereas it had no effect on cholesterol efflux to control
      plasma. A strong positive correlation was established between percent cAMP
      stimulation of efflux and plasma hapo A-II concentration. The cAMP stimulation of
      efflux to hAIItg mouse plasma may be linked to the presence of pre-beta migrating
      HDL containing hapo A-II. Thus, despite lower HDL and apolipoprotein A-I
      contents, the increased ability of plasma from hAIItg mice to extract cholesterol
      from macrophage-like cells may have an antiatherogenic influence.

PMID- 11950704
TI  - Inhibitory effect on arterial injury-induced neointimal formation by adoptive B
      cell transfer in Rag-1 knockout mice.
AB  - We investigated the effect of B-cell reconstitution in immune-deficient Rag-1
      knockout (KO) mice subjected to arterial injury. After 21 days, injury induced a
      4- to 5-fold increase in neointimal formation in Rag-1 KO mice fed normal chow
      compared with wild-type (WT) mice (0.020+/-0.0160 [n=8] versus 0.0049+/-0.0022
      [n=8] mm(2), respectively; P<0.05) and in western-type diet-fed Rag-1 KO mice
      compared with WT mice (0.0312+/-0.0174 [n=7] versus 0.0050+/-0.0028 [n=6] mm(2),
      respectively; P<0.05). To investigate the role of B cells in response to injury,
      Rag-1 KO mice were reconstituted with B cells derived from the spleens of WT
      mice, with donors and recipients on the same diet. Reconstitution of Rag-1 KO
      mice with B cells from WT mice (both fed normal chow) reduced neointimal
      formation compared with the effect in unreconstituted Rag-1 KO mice (0.0076+/
      0.0039 [n=9] versus 0.020+/-0.0160 [n=8] mm(2), respectively; P<0.05).
      Reconstitution of Rag-1 KO mice with B cells from WT mice (both fed a western
      diet) reduced neointimal formation compared the effect in Rag-1 KO mice (0.0087+/
      0.0037 [n=8] versus 0.0312+/-0.0174 [n=7] mm(2), respectively; P<0.05). Injured
      carotid arteries from reconstituted Rag-1 KO mice had detectable IgM and IgG,
      indicating viable transfer of B cells. The results suggest that B cells modulate
      the response to arterial injury.

PMID- 11950705
TI  - Atherosclerosis in C3H/HeJ mice reconstituted with apolipoprotein E-null bone
      marrow.
AB  - Previous studies showed that reconstitution of atherosclerosis-susceptible
      C57BL/6 (B6) female mice with apolipoprotein E (apoE)-deficient (apoE(-/-)) bone
      marrow resulted in markedly increased atherosclerosis, despite the fact that
      plasma lipid levels were unchanged. To determine whether apoE(-/-) bone marrow
      would increase atherosclerosis in an atherosclerosis-resistant strain, female
      C3H/HeJ (C3H) mice were lethally irradiated and reconstituted with bone marrow
      from either C3H.apoE(-/-) mice or wild-type C3H mice. Four weeks after
      transplantation, the mice were fed an atherogenic diet for 12 weeks. We found
      that reconstitution of C3H mice with apoE(-/-) bone marrow resulted in a slight
      reduction in plasma apoE levels and a dramatic reduction in apoE and
      apolipoprotein B (apoB) in the aortic wall. Plasma apoB and cholesterol levels
      were unchanged, as were atherosclerotic lesions at the aortic root. These data
      indicate that reconstitution of C3H mice with apoE(-/-) bone marrow has no effect
      on atherosclerosis susceptibility and that apoE promotes accumulation of apoB in
      the vessel wall.

PMID- 11950706
TI  - Elevated soluble cellular adhesion molecules in subjects with low HDL
      cholesterol.
AB  - The purpose of this study was to investigate whether the expression of cellular
      adhesion molecules (CAMs) is enhanced in individuals with low HDL cholesterol
      (HDL-C). Plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1),
      intercellular adhesion molecule-1 (sICAM-1), and E-selectin (sE-selectin) were
      measured in subjects with low (below the 10th percentile for the Italian
      population), average, or high (above the 90th percentile) HDL-C. Average sICAM-1
      and sE-selectin levels were significantly higher in two groups of 65 individuals
      with low HDL levels, either hyperlipidemic (320.5+/-16.0 and 61.4+/-3.5 ng/mL) or
      normolipidemic (309.6+/-13.0 and 60.0+/-2.7 ng/mL), than in subjects with average
      HDL levels, either hyperlipidemic (267.0+/-10.1 and 50.4+/-2.8 ng/mL) or
      normolipidemic (257.9+/-5.4 and 51.1+/-2.4 ng/mL), or with high HDL levels
      (254.8+/-10.2 and 52.5+/-3.2 ng/mL). No significant difference was found in the
      plasma sVCAM-1 concentration. HDL-C was inversely correlated with sICAM-1 and sE
      selectin in the low-HDL subjects (r(2)=0.087 and 0.035, P=0.0007 and 0.033,
      respectively), but not in individuals with normal or elevated HDL-C (r(2)=0.012
      and 0.006). A fenofibrate-induced increase of HDL-C in 20 low-HDL subjects was
      associated with a significant reduction of plasma sICAM-1 and sE-selectin
      concentrations. An increased CAMs expression may be a mechanism by which a low
      plasma HDL level promotes atherogenesis and causes acute atherothrombotic events.

PMID- 11950707
TI  - Increased circulating malondialdehyde-modified LDL levels in patients with
      coronary artery diseases and their association with peak sizes of LDL particles.
AB  - Recent establishment of a sensitive ELISA system using antibodies against
      malondialdehyde-modified low density lipoprotein (MDA-LDL) made it possible to
      determine the circulating oxidized lipoprotein levels. Here, we investigated the
      serum levels of MDA-LDL in 62 patients with coronary artery disease (CAD)
      compared with the levels in 42 patients without CAD [groups CAD(+) and CAD(-),
      respectively], which are adjusted for age, serum total cholesterol, LDL and high
      density lipoprotein cholesterol, and triglyceride levels. Serum MDA-LDL levels
      were 113.4+/-49.1 IU/L in CAD(+), which were significantly higher than the levels
      in CAD(-) (85.2+/-22.5 IU/L, P<0.0005). The ratio of MDA-LDL/LDL cholesterol was
      0.95+/-0.32 in CAD(+), indicating a significant increase compared with the ratio
      in CAD(-) (0.68+/-0.19, P<0.0005). The positive correlation of MDA-LDL level and
      the ratio of MDA-LDL/LDL cholesterol with intima-media thickness in carotid
      arteries was observed. Age was not clearly associated with the MDA-LDL level
      (P=0.865). The serum MDA level was positively correlated with LDL cholesterol
      (P<0.0001) and with triglycerides (P<0.001) and negatively correlated with high
      density lipoprotein cholesterol (P<0.05). Furthermore, the MDA-LDL level was
      negatively correlated with the peak size of the LDL particle (P<0.01). The LDL
      subclasses that were identified by using the sera collected from the subjects by
      sequential ultracentrifugation showed that the ratios of MDA-LDL/apolipoprotein B
      in LDL3 and LDL4 were nearly 3-fold higher than those in LDL1 and LDL2 for CAD(+)
      and CAD(-). These results indicate that the circulating MDA-LDL level is
      increased in CAD(+), independent of the serum LDL cholesterol level but in
      association with the peak size of LDL particles. The measurement of serum MDA-LDL
      level may be useful for the identification of patients with advanced
      atherosclerosis.

PMID- 11950708
TI  - Contribution of hepatic lipase, lipoprotein lipase, and cholesteryl ester
      transfer protein to LDL and HDL heterogeneity in healthy women.
AB  - Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) have been
      independently associated with low density lipoprotein (LDL) and high density
      lipoprotein (HDL) size in different cohorts. These studies have been conducted
      mainly in men and in subjects with dyslipidemia. Ours is a comprehensive study of
      the proposed biochemical determinants (lipoprotein lipase, HL, CETP, and
      triglycerides) and genetic determinants (HL gene [LIPC] and Taq1B) of small dense
      LDL (sdLDL) and HDL subspecies in a large cohort of 120 normolipidemic,
      nondiabetic, premenopausal women. HL (P<0.001) and lipoprotein lipase activities
      (P=0.006) were independently associated with LDL buoyancy, whereas CETP (P=0.76)
      and triglycerides (P=0.06) were not. The women with more sdLDL had higher HL
      activity (P=0.007), lower HDL2 cholesterol (P<0.001), and lower frequency of the
      HL (LIPC) T allele (P=0.034) than did the women with buoyant LDL. The LIPC
      variant was associated with HL activity (P<0.001), HDL2 cholesterol (P=0.034),
      and LDL buoyancy (P=0.03), whereas the Taq1B polymorphism in the CETP gene was
      associated with CETP mass (P=0.002) and HDL3 cholesterol (P=0.039). These results
      suggest that HL activity and HL gene promoter polymorphism play a significant
      role in determining LDL and HDL heterogeneity in healthy women without
      hypertriglyceridemia. Thus, HL is an important determinant of sdLDL and HDL2
      cholesterol in normal physiological states as well as in the pathogenesis of
      various disease processes.

PMID- 11950709
TI  - Combined endothelin receptor blockade evokes enhanced vasodilatation in patients
      with atherosclerosis.
AB  - Endothelin (ET)-1 causes vasoconstriction via ET(A) and ET(B) receptors located
      on vascular smooth muscle cells and vasodilatation via ET(B) receptors on
      endothelial cells. Studies in vitro indicate an upregulation of ET(B) receptors
      in atherosclerosis. The present study investigated the vascular effects evoked by
      endogenous ET-1 in atherosclerotic patients. Forearm blood flow (FBF) was
      measured with venous occlusion plethysmography in 10 patients with
      atherosclerosis and in 10 healthy control subjects during intra-arterial infusion
      of selective ET receptor antagonists. The ET(B) receptor antagonist BQ788 evoked
      a significant increase in FBF (31+/-13%) in the patients, whereas a 20+/-9%
      reduction was observed in the control subjects. The ET(A) receptor antagonist
      BQ123 combined with BQ788 evoked a marked increase in FBF (102+/-25%) in the
      patients compared with no effect in the control subjects (-3+/-9%, P<0.001 versus
      patients). The ET(A) receptor antagonist BQ123 increased FBF to a similar degree
      in patients (39+/-11%) as in control subjects (41+/-11%). The increase in FBF
      evoked by selective ET(A) receptor blockade was significantly (P<0.05) less than
      that evoked by combined ET(A)/ET(B) receptor blockade in the atherosclerotic
      patients. These observations suggest an enhanced ET-1-mediated vascular tone in
      atherosclerotic patients, which is at least partly due to increased ET(B)
      mediated vasoconstriction.

PMID- 11950710
TI  - Hypercholesterolemia enhances thromboembolism in arterioles but not venules:
      complete reversal by L-arginine.
AB  - We investigated in vivo the effect of cholesterol diet-induced
      hypercholesterolemia (HC) on thromboembolism in nonatherosclerotic rabbit
      mesenteric arterioles and venules (diameter 21 to 45 micrometer). After
      mechanical vessel wall injury, the ensuing thromboembolic reaction was studied by
      intravital videomicroscopy. A dramatic prolongation of embolization duration
      (median >600 seconds) was observed in the arterioles of the HC group compared
      with the arterioles of a normal chow-fed (NC) control group (142 seconds,
      P<0.0001); concomitantly, relative thrombus height increased (thrombus
      height/vessel diameter was 68% for the HC group and 58% for the NC group;
      P<0.05). By contrast, in venules, cholesterol did not affect embolization
      duration (42 seconds for HC group, 34 seconds for NC group) and thrombus height
      (66% for HC group, 64% for NC group). Furthermore, the role of endothelial NO
      synthesis was studied. In arterioles, stimulation of endogenous NO synthesis
      through mesenteric superfusion of L-arginine (1 mmol/L) completely reversed
      cholesterol-enhanced embolization (152 seconds) but did not influence thrombus
      height (63%). L-Arginine had no effect in venules of the HC group (51 seconds)
      and nor in the arterioles and venules of the NC group (177 seconds for
      arterioles, 43 seconds for venules). This study indicates that
      hypercholesterolemia selectively enhances thrombus formation and embolization in
      arterioles but not in venules and that stimulation of endogenous NO production
      antagonizes this enhancement of arteriolar thromboembolism.

PMID- 11950711
TI  - Role of ADP receptor P2Y(12) in platelet adhesion and thrombus formation in
      flowing blood.
AB  - ADP plays a central role in regulating platelet function. It induces platelet
      aggregation via the activation of 2 major ADP receptors, P2Y(1) and P2Y(12). We
      have investigated the role of P2Y(12) in platelet adhesion and thrombus formation
      under physiological flow by using blood from a patient with a defect in the gene
      encoding P2Y(12). Anticoagulated blood from the patient and from healthy
      volunteers was perfused over collagen-coated coverslips. The patient's thrombi
      were smaller and consisted of spread platelets overlying platelets that were not
      spread, whereas control thrombi were large and densely packed. Identical platelet
      surface coverage, aggregate size, and morphology were found when a P2Y(12)
      antagonist, N(6)-(2-methylthioethyl)-2-(3,3,3-trifluoropropylthio)-beta,gamma
      dichloromethylene ATP (also known as AR-C69931 MX), was added to control blood.
      The addition of a P2Y(1) antagonist (adenosine-3',5'-diphospate) to control blood
      resulted in small, but normally structured, thrombi. Thus, the ADP-P2Y(12)
      interaction is essential for normal thrombus buildup on collagen. The patient's
      blood also showed reduced platelet adhesion on fibrinogen, which was not due to
      changes in morphology. Comparable results were found by using control blood with
      AR-C69931 MX and also with adenosine-3',5'-diphospate. This suggested that
      P2Y(12) and P2Y(1) were both involved in platelet adhesion on immobilized
      fibrinogen, thereby revealing it as ADP dependent. This was confirmed by complete
      inhibition on the addition of creatine phosphate/creatine phosphokinase.

PMID- 11950712
TI  - Fluvastatin reduces tissue factor expression and macrophage accumulation in
      carotid lesions of cholesterol-fed rabbits in the absence of lipid lowering.
AB  - The expression of tissue factor (TF), mainly by infiltrated inflammatory cells,
      has been shown to be responsible for the thrombogenicity associated with
      atheroma. The contribution of the nonlipid-related effects of statins to the
      clinical benefits of statin therapy is currently under intense investigation. In
      this study, we evaluated the ability of fluvastatin to modulate TF expression and
      macrophage accumulation in rabbit carotid intimal lesions independently of
      cholesterol lowering. Male rabbits were fed for 30 days a 1% cholesterol-rich
      diet with or without fluvastatin at 5 mg/kg per day. Two weeks from the start of
      treatment, a silastic collar was placed around the carotid artery. Fifteen days
      later, the animals were killed, and carotid segments were excised and processed.
      The atherogenic diet caused a consistent increase in plasma cholesterol levels
      (610+/-231 mg/dL versus 50+/-9 mg/dL at baseline), which were not affected by
      fluvastatin (603+/-248 mg/dL). In the rabbits fed a high cholesterol diet without
      fluvastatin, an intimal lesion with macrophage accumulation and TF expression was
      detected. Fluvastatin significantly reduced TF and macrophage content of the
      lesion (-50% for both). Results indicate that fluvastatin may attenuate the
      inflammatory and thrombogenic potential of atherosclerotic lesions through a
      mechanism(s) other than cholesterol reduction, providing new insight regarding
      the complex mode of action of statins.

PMID- 11950713
TI  - Folic acid treatment reduces chemokine release from peripheral blood mononuclear
      cells in hyperhomocysteinemic subjects.
AB  - Elevated plasma homocysteine concentration is an independent risk factor for
      cardiovascular disease. However, the mechanisms by which hyperhomocysteinemia
      induces vascular disease are uncertain. An early step in atherogenesis involves
      leukocyte migration into the arterial wall, a process regulated in part by
      chemokines. We hypothesized that homocysteine may exert its atherogenic effect in
      part through chemokine-mediated mechanisms, and in the present study, we examined
      the effects of folic acid supplementation for 6 weeks on chemokine levels in
      hyperhomocysteinemic individuals. Data showed the following: (1) Compared with
      control subjects, hyperhomocysteinemic subjects had elevated plasma levels of the
      CXC chemokines, epithelial neutrophil-activating peptide (ENA)-78 (P<0.05), and
      growth-regulated oncogene (GRO)alpha (P=0.088), and homocysteine was
      significantly correlated with ENA-78 and GROalpha. (2) During folic acid
      treatment, normalization of homocysteine levels was accompanied by a marked
      reduction in oxidized low density lipoprotein-stimulated release of CXC
      chemokines (ie, GROalpha, ENA-78, and interleukin-8) and CC chemokines (ie,
      monocyte chemoattractant peptide-1 and RANTES) in peripheral blood mononuclear
      cells from these individuals. (3) The oxidized low density lipoprotein-induced
      release of ENA-78 from peripheral blood mononuclear cells from control subjects
      was significantly reduced when cells were incubated in the presence of folic
      acid. These data may suggest that homocysteine exerts atherogenic effects in part
      by enhancing chemokine responses in cells involved in atherogenesis and that
      folic acid supplementation may downregulate these inflammatory responses.

PMID- 11950715
TI  - Expression of the novel scavenger receptor SR-PSOX in cultured aortic smooth
      muscle cells and umbilical endothelial cells.

PMID- 11950714
TI  - Tissue plasminogen activator, fibrin D-dimer, and insulin resistance in the
      relatives of patients with premature coronary artery disease.
AB  - Elevated levels of tissue-type plasminogen activator antigen (tPA), fibrinogen,
      and fibrin D-dimer predict coronary artery disease (CAD) events and stroke. These
      factors, possibly in association with insulin resistance, may be important in
      families in which CAD has become clinically apparent at a premature age. From 125
      patients with angiographically confirmed, premature CAD, 175 healthy male
      relatives (age </=65 years) were identified. One hundred seventy-five healthy
      volunteers of similar age and without any family history of CAD were recruited.
      There were no differences between relatives and controls in terms of conventional
      CAD risk factors, cigarette smoking, alcohol consumption, or cardiorespiratory
      fitness. Estimated insulin resistance and plasminogen activator inhibitor 1
      levels were not increased in relatives. Fibrin D-dimer, tPA, and fibrinogen
      levels were elevated in relatives compared with controls, 55 (52 to 58) ng/mL
      versus 49 (45 to 53) ng/mL, P<0.01, for D-dimer; 8.0 (7.5 to 8.6) ng/mL versus
      5.6 (5.2 to 6.1) ng/mL, P<0.001, for tPA; and 3.0 (2.9 to 3.1) g/L versus 2.8
      (2.7 to 2.9) g/L, P<0.05, for fibrinogen. These differences remained after
      adjustment for correlates, including fibrinogen, age for D-dimer, and features of
      the insulin resistance syndrome for tPA. tPA and D-dimer levels are elevated in
      the healthy, male, first-degree relatives of patients with premature CAD. This
      association is independent of potential confounding factors.

PMID- 11950716
TI  - Too much medicine?

PMID- 11950717
TI  - Health: perception versus observation.

PMID- 11950718
TI  - The medicalisation of old age.

PMID- 11950719
TI  - Genetics and medicalisation.

PMID- 11950720
TI  - Medicalisation, limits to medicine, or never enough money to go around?

PMID- 11950721
TI  - Medicalisation: peering from inside medicine.

PMID- 11950722
TI  - Drug firms hype disease as sales ploy, industry chief claims.

PMID- 11950725
TI  - Claims of clone pregnancy could threaten US stem cell research.

PMID- 11950726
TI  - Strategy needed for mental health of women prisoners.

PMID- 11950727
TI  - Dutch GPs warned against new contraceptive pill.

PMID- 11950728
TI  - Arthritis drug should be removed from market, says consumer group.

PMID- 11950729
TI  - Scotland to start screening programme for diabetic retinopathy.

PMID- 11950730
TI  - "Bubble baby" lives a normal life after gene therapy.

PMID- 11950732
TI  - Medicare will now cover some treatments for Alzheimer's disease.

PMID- 11950733
TI  - Outcome of expectant management of spontaneous first trimester miscarriage:
      observational study.
AB  - OBJECTIVES: To evaluate the uptake and outcome of expectant management of
      spontaneous first trimester miscarriage in an early pregnancy assessment unit.
      PARTICIPANTS: 1096 consecutive patients with a diagnosis of spontaneous first
      trimester miscarriage. METHODS: Each miscarriage was classified as complete,
      incomplete, missed, or anembryonic on the basis of ultrasonography. Women who
      needed treatment were given the choice of expectant management or surgical
      evacuation of retained products of conception under general anaesthesia. Women
      undergoing expectant management were checked a few days after transvaginal
      bleeding had stopped, or they were monitored at weekly intervals for four weeks.
      MAIN OUTCOME MEASURES: A complete miscarriage (absence of transvaginal bleeding
      and endometrial thickness <15 mm), the number of women completing their
      miscarriage within each week of management, and complications (excessive pain or
      transvaginal bleeding necessitating hospital admission or clinical evidence of
      infection). RESULTS: Two patients with molar pregnancies were excluded, and 37%
      of the remainder (408/1094) were classified as having had a complete miscarriage.
      70% (478/686) of women with retained products of conception chose expectant
      management; of these, 27 (6%) were lost to follow up. A successful outcome
      without surgical intervention was seen in 81% of cases (367/451). The rate of
      spontaneous completion was 91% (201/221) for those cases classified as incomplete
      miscarriage, 76% (105/138) for missed miscarriage, and 66% (61/92) for
      anembryonic pregnancy. 70% of women completed their miscarriage within 14 days of
      classification (84% for incomplete miscarriage and 52% for missed miscarriage and
      anembryonic pregnancy). CONCLUSIONS: Most women with retained products of
      conception chose expectant management. Ultrasonography can be used to advise
      patients on the likelihood that their miscarriage will complete spontaneously
      within a given time.

PMID- 11950734
TI  - Treatment of imported malaria in an ambulatory setting: prospective study.

PMID- 11950735
TI  - Hepatitis B immunisation in renal units in the United Kingdom: questionnaire
      study.

PMID- 11950736
TI  - Workplace bullying in junior doctors: questionnaire survey.

PMID- 11950737
TI  - Drug points: Neuropsychiatric complications of nevirapine treatment.

PMID- 11950738
TI  - Evolving general practice consultation in Britain: issues of length and context.

PMID- 11950739
TI  - In search of "non-disease".

PMID- 11950740
TI  - Selling sickness: the pharmaceutical industry and disease mongering.

PMID- 11950741
TI  - Has the medicalisation of childbirth gone too far?

PMID- 11950742
TI  - Sexual behaviour and its medicalisation: in sickness and in health.

PMID- 11950743
TI  - The limits of psychiatry.

PMID- 11950744
TI  - Between hope and acceptance: the medicalisation of dying.

PMID- 11950745
TI  - For and against: Direct to consumer advertising is medicalising normal human
      experience: For.

PMID- 11950746
TI  - For and against: Direct to consumer advertising is medicalising normal human
      experience: Against.

PMID- 11950747
TI  - What do you think is a non-disease? Pros and cons of medicalisation.

PMID- 11950748
TI  - Editorial on CFS was biased, inaccurate, and misleading.

PMID- 11950749
TI  - Gulf war syndrome may be post-conflict dysfunction.

PMID- 11950750
TI  - ICD and DSM are contemporary cultural documents.

PMID- 11950751
TI  - Hormone replacement therapy and the breast. Women still want to have hormone
      replacement therapy.

PMID- 11950752
TI  - Hormone replacement therapy and the breast. Studies must determine the evidence.

PMID- 11950753
TI  - Schizophrenia in ethnic minority groups. Selection bias in prevalence data is
      difficult to rule out.

PMID- 11950755
TI  - Fortification of flour with folic acid. Fortification has several potential
      risks.

PMID- 11950754
TI  - Antiplatelet therapy and atherosclerotic events. Commentary is inaccurate.

PMID- 11950756
TI  - Treatment of intersex needs open discussion.

PMID- 11950757
TI  - Doctors' knowledge of radiation exposures is deficient.

PMID- 11950758
TI  - Prevalence of surnames in each letter affects order of authors.

PMID- 11950763
TI  - Early specification of the hierarchical organization of visual cortical areas in
      the macaque monkey.
AB  - The laminar organization of cortico-cortical projection neurons (expressed by the
      percentage of supragranular projecting neurons - SLN%) characterizes cortical
      pathways as feedforward (FF) or feedback (FB) and determines the hierarchical
      ranking of cortical areas. There is evidence of a developmental reduction in SLN%
      of pathways to area V1. Here, by analyzing pre- and postnatal projections to area
      V4, we have been able to address whether developmental reductions of SLN% impact
      on information processing in the immature cortex. FB pathways to area V4 exhibit
      28-84% reduction of SLN%. This contrasts with the FF projections, which show
      little or no SLN% reduction. However, SLN% values in the immature cortex
      allocated cortical areas to the same hierarchical levels as in the adult. The
      developmental reduction of SLN% is a widespread phenomenon in the neocortex and
      is a distinctive feature of FB pathways. Two mechanisms contribute to
      developmental changes in SLN%: (i) delayed ingrowth of axons into the cortical
      target from infragranular layer neurons and (ii) prolonged developmental
      reduction of the divergence of projections from supragranular layer neurons. The
      present results show that FF and FB projections exhibit different developmental
      processes and patterns of connections linking cortical areas and their
      hierarchical relations are established prenatally, independently of regressive
      phenomena.

PMID- 11950764
TI  - Temporal relation of population activity in visual areas MT/MST and in primary
      motor cortex during visually guided tracking movements.
AB  - There is growing evidence that in primate cerebral cortex the areas along the
      'dorsal pathway' are involved in the transformation of visual motion information
      towards a motor command. To pursue this cortical flow of information from visual
      motion areas to the motor cortex, single-cell activity was recorded from visual
      areas MT/MST (middle temporal area/medial superior temporal area) and from
      primary motor cortex (M1) while monkeys tracked moving targets with their right
      hand. Spike activity of 353 directionally tuned motor cortex cells was combined
      to a time-varying population vector, and similarly a time-resolved visual
      population vector was calculated from 252 MT/MST cells. Both population vectors
      code faithfully for the direction of the collinear motion of target and hand. For
      a given direction, the length of the population vectors varied over time during
      the performance of the task. The temporal evolution of both population responses
      reflects the different relationship between the early visual responses to the
      moving target and the directional motor command controlling the hand movement.
      The results indicate that during the visual tracking task visual and motor
      populations which code for similar directions of movement are co-activated with
      considerable temporal overlap. Despite this co-activation in both modalities, we
      failed to observe any significant synchronization between areas MT/MST and M1.

PMID- 11950765
TI  - Recruitment of anterior dorsolateral prefrontal cortex in human reasoning: a
      parametric study of relational complexity.
AB  - Reasoning and problem solving depend on the ability to represent and integrate
      complex relationships among stimuli. For example, deciding whether an animal is
      dangerous requires integrating information about the type of animal, its size,
      its distance from oneself, and one's proximity to shelter. Relational complexity
      increases with the number of such interdependent elements that must be
      simultaneously considered to solve a problem. We used functional magnetic
      resonance imaging to identify brain regions that respond selectively in
      processing high levels of relational complexity. Performance on nonverbal
      reasoning problems in which relational complexity was varied parametrically was
      compared with performance on control problems in which relational complexity was
      held constant while difficulty was manipulated by adding distractor forms to the
      problems. Increasing complexity and adding distractors both led to increased
      activation in parietal and in dorsolateral prefrontal cortex, with high levels of
      relational complexity selectively activating anterior left prefrontal cortex. Our
      data provide evidence that brain regions specific to integrating complex
      relations among stimuli are distinct from those involved in coping with general
      task difficulty and with working-memory demands.

PMID- 11950766
TI  - Brain volumes and surface morphology in monozygotic twins.
AB  - Because healthy monozygotic twins share an identical genetic complement, they
      provide a unique opportunity to explore the genetic and environmental
      determinants of brain development. The purpose of this study was to evaluate the
      similarities between measures of cerebral and subcortical volumes and surface
      morphology in monozygotic twins compared with a matched control sample.
      Combinations of automated and manual methods were used to evaluate total brain
      volume, gray matter, white matter, ventricles and volumes of the frontal,
      temporal, parietal and occipital lobes. An artificial neural network algorithm
      was used to measure the cerebellum, thalamus, caudate and putamen. Measures of
      surface morphology included an index of gyral and sulcal curvature, surface area
      and cortical depth. The cerebral volume regions, including the gray matter, white
      matter and lobar volumes, were highly correlated within monozygotic twin pairs,
      with nearly all correlation coefficients >0.90. The cerebellum was also highly
      correlated (r = 0.99). Reasonably high correlations were found for the cortical
      depth (r = 0.84), caudate (r = 0.84), thalamus (r = 0.75) and putamen (r = 0.75).
      The surface measures, however, demonstrated the least correlation within twin
      pairs and thus are more prone to environmental influences. The high to moderate
      correlations between MZ twins compared with the matched controls highlights the
      role of heredity in both prenatal and postnatal neurodevelopment.

PMID- 11950768
TI  - Spatial focusing of neuronal responses induced by asynchronous two-tone stimuli
      in the guinea pig auditory cortex.
AB  - Spatiotemporal patterns of neuronal responses to asynchronous two-tone stimuli in
      the anterior field of the auditory cortex of anesthetized guinea pigs were
      studied using an optical recording method (12 x 12 photodiode array, voltage
      sensitive dye RH795). Interactions between the onset response to the first tone
      (masker; 5, 8, 10, 12 and 15 kHz, 200 ms) and to the second tone (probe; 10 kHz,
      30 ms) with onset delays relative to the masker onset (0, 5, 10, 15 and 20 ms)
      were investigated. In general, two-tone interaction was suppressive rather than
      facilitative. At 0-10 ms probe delays, two-tone responses induced in the probe
      isofrequency area on the cortex tended to fuse with the masker response. At 15-20
      ms probe delays, the probe response was apparently reduced, but was spatially
      focused and separated from the masker response. This spatial focusing of the
      probe response may have been due to neuronal inhibition originating after the
      masker onset response. These results are in agreement with psychoacoustical
      observations in human subjects, such as auditory segregation, and indicate that
      the spatial focusing of the cortical response provides a neuronal basis for
      detecting slightly asynchronous auditory inputs.

PMID- 11950767
TI  - Greater orbital prefrontal volume selectively predicts worse working memory
      performance in older adults.
AB  - Alterations of the prefrontal cortex (PFC) could contribute to cognitive decline
      in older adults. We examined the specificity of age-related PFC degeneration and
      whether cognitive abilities were related to volumetric measurements. Older and
      younger subjects were tested using a battery of tasks supported by different
      subregions within the PFC. The cognitive data from older subjects were related to
      PFC volumetric measurements in order to determine whether cortical morphology was
      predictive of individual differences in task performance within this age range
      (72-94 years). Working memory performance best distinguished older from younger
      subjects. Working memory measures but not other measures were correlated with age
      in both groups. A larger orbital PFC volume was related to a worse working memory
      performance and a larger superior PFC volume was related to worse conditional
      association learning. The volumes of these regions were not related to
      performance on other tasks. These results suggest that working memory is a
      sensitive measure of cognitive aging and that regional morphology is associated
      with specific cognitive abilities in older adults.

PMID- 11950769
TI  - Similar perisynaptic glial localization for the Na+,K+-ATPase alpha 2 subunit and
      the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex.
AB  - Several isoenzymes of the Na(+),K(+)-ATPase are expressed in brain but their
      specific roles are poorly understood. Recently, it was suggested that an
      isoenzyme of the Na(+),K(+)-ATPase containing the alpha(2) subunit, together with
      the glutamate transporters GLAST and GLT-1, participate in a coupling mechanism
      between neuronal activity and energy metabolism taking place in astrocytes. To
      substantiate this hypothesis, we compared the distribution of alpha(2), GLAST
      and/or GLT-1 in the rat cerebral cortex using double immunofluorescence and
      confocal microscopy, and immunocytochemistry at the electron microscopic level.
      We also investigated the relationship between alpha(2), GLAST or GLT-1 and
      asymmetrical synaptic junctions (largely glutamatergic) and GABAergic nerve
      terminals. Results show that the alpha(2) subunit has an exclusive astroglial
      localization, and that it is almost completely co-distributed with GLAST and GLT
      1 when evaluated by confocal microscopy. This similar distribution was confirmed
      at the ultrastructural level, which further showed that the vast majority of the
      alpha(2) staining (73% of all labelled elements), like that of GLAST and GLT-1,
      was located in glial leaflets surrounding dendritic spines and the dendritic
      and/or axonal elements of asymmetrical (glutamatergic) axo-dendritic synapses.
      Synapses ensheathed by alpha(2), GLAST or GLT-1 virtually never included (<or=2%)
      GABAergic nerve terminals or synaptic junctions. However, a subset of GABAergic
      nerve terminals (10-14%) were directly apposed to asymmetrical axo-dendritic
      junctions surrounded by alpha(2), GLAST or GLT-1. Altogether these results
      demonstrate that alpha(2), GLAST and GLT-1 have comparable perisynaptic
      distribution within cortical astrocytes most likely associated with glutamatergic
      synapses.

PMID- 11950770
TI  - Cocaine sensitization: modulation by dopamine D2 receptors.
AB  - Repeated administration of cocaine progressively increases drug-induced locomotor
      activity. This study examined the role of dopamine D(1)- and D(2)-like receptors
      in the medial prefrontal cortex (mPFC) in mediating these sensitized behaviors.
      For initiation experiments, animals received bilateral intra-mPFC injections of
      either saline, the D(1)-like agonist SKF 81297 (3 nmol/side) or the D(2)-like
      agonist quinpirole (5 nmol/side) 5 min before each of four daily peripheral
      injections of saline or cocaine (15 mg/kg i.p.). Following 1 week of withdrawal,
      the animals were challenged with a systemic injection of cocaine. For expression
      studies, the animals received four daily systemic injections of either saline or
      cocaine and 1 week later were pre-treated with an intra-mPFC injection of saline,
      SKF 81297 or quinpirole 5 min before receiving a systemic challenge injection of
      cocaine. Intra-mPFC injection of quinpirole blocked the initiation and attenuated
      the expression of cocaine -induced behavioral sensitization. In contrast, intra
      mPFC SKF 81297 did not alter the induction or expression of behavioral
      sensitization to cocaine at the dose tested. In addition, in vivo microdialysis
      studies demonstrated that intracortical quinpirole administration blocked the
      initiation and blunted the expression of cocaine-induced neurochemical
      sensitization, as defined by augmented dopamine concentrations in the nucleus
      accumbens. Collectively, the results show that activation of D(2)-like receptors
      in the mPFC may alter the enduring changes responsible for the development of
      cocaine sensitization.

PMID- 11950771
TI  - Laminar organization of the human fetal cerebrum revealed by histochemical
      markers and magnetic resonance imaging.
AB  - The developing human cerebrum displays age-specific changes in its patterns of
      lamination. Among these, the subplate zone is the most prominent transient
      compartment because growing major afferent systems temporarily reside in this
      zone, establish synapses and take part in cellular interactions that are crucial
      for subsequent cortical development. We explored the potential of magnetic
      resonance imaging (MRI) for tracing the developmental history of the most
      prominent cortical layer (the subplate zone) and other laminar compartments of
      the fetal cerebral wall between 15 and 36 weeks post-ovulation. We found that
      changes in the MRI lamination pattern of the human fetal cerebral wall are
      predominantly caused by changes in the subplate zone. Histochemical staining of
      the extracellular matrix (ECM) enables selective visualization of the subplate
      zone and correlation with an increase in MRI signal intensity in the subplate
      zone and ingrowth and accumulation of thalamocortical and corticocortical
      afferents and their subsequent relocation to the cortical plate. Thus, dynamic
      changes in the MRI appearance of the subplate zone and histochemical staining of
      its ECM can be used as indirect parameters for an assessment of normal versus
      disturbed unfolding of crucial histogenetic events that are involved in prenatal
      shaping of the human cerebral cortex.

PMID- 11950772
TI  - Experience-dependent modulation of category-related cortical activity.
AB  - Naming pictures of objects from different categories (e.g. animals or tools)
      evokes maximal responses in different brain regions. However, these 'category
      specific' regions typically respond to other object categories as well. Here we
      used stimulus familiarity to further investigate category representation. Naming
      pictures of animals and tools elicited category-related activity in a number of
      previously identified regions. This activity was reduced for familiar relative to
      novel stimuli. Reduced activation occurred in all object responsive areas in the
      ventral occipito-temporal cortex, regardless of which category initially produced
      the maximal response. This suggests that object representations in the ventral
      occipito-temporal cortex are not limited to a discrete area, but rather are
      widespread and overlapping. In other regions (e.g. the lateral temporal and left
      premotor cortices), experience-dependent reductions were category specific.
      Together, these findings suggest that category-related activations reflect the
      retrieval of information about category-specific features and attributes.

PMID- 11950773
TI  - Northern blot and in situ hybridization analyses of MARCKS mRNA expression in the
      cerebral cortex of the macaque monkey.
AB  - Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major substrate for
      protein kinase C, and is involved in synaptic plasticity. Using both Northern
      blot and in situ hybridization techniques, we investigated whether MARCKS
      expression varied according to the cerebral region, including the hippocampal
      formation, or according to the type of neuron. Northern blot analysis showed that
      the MARCKS mRNA level was higher in the association areas than in the primary
      sensory and motor areas of the cerebral neocortex. MARCKS mRNA levels in the
      hippocampus and the amygdala were as high as those in the association areas. The
      in situ hybridization experiments confirmed the Northern blot results and showed
      the distribution and characteristics of MARCKS mRNA-positive neurons. In the
      association areas of the neocortex, prominent signals were observed in neurons in
      layers II-VI. In the primary areas, prominent signals were restricted to neurons
      in layers IV-VI. In the hippocampus, the most intense hybridization signals were
      observed in neurons in the granule cell layer of the dentate gyrus. The observed
      region-specific expression might reflect functional specialization for plasticity
      in individual regions of the monkey cerebral cortex.

PMID- 11950775
TI  - Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and
      3-hydroxylation.
AB  - Coumarin, a widely used fragrance ingredient, is a rat liver and mouse lung
      toxicant. Species differences in toxicity are metabolism-dependent, with injury
      resulting from the cytochrome P450-mediated formation of coumarin 3,4-epoxide
      (CE). In this study, the enzymes responsible for coumarin activation in liver and
      lung were determined. Recombinant human and rat CYP1A forms and recombinant human
      CYP2E1 readily catalyzed CE production. Coinhibition with CYP1A1/2 and CYP2E1
      antibodies blocked CE formation by 38, 84, and 67 to 92% (n = 3 individual
      samples) in mouse, rat, and human hepatic microsomes, respectively. Although
      CYP1A and 2E forms seem to be the most active catalysts of CE formation in liver,
      studies conducted with the mechanism-based inhibitor 5-phenyl-pentyne
      demonstrated that CYP2F2 is responsible for up to 67% of CE formation in whole
      mouse lung microsomes. In contrast to the CE pathway, coumarin 3-hydroxylation is
      a minor product of coumarin in liver microsomes from mice, rats, and humans and
      is catalyzed predominately by CYP3A and CYP1A forms, confirming that CE and 3
      hydroxycoumarin are formed via distinct metabolic pathways.

PMID- 11950774
TI  - Effects of a P-glycoprotein inhibitor on brain and plasma concentrations of anti
      human immunodeficiency virus drugs administered in combination in rats.
AB  - Most of the existing anti-human immunodeficiency virus agents enter the central
      nervous system (CNS) inefficiently and thus may allow slow viral replication in
      the brain. This may provide a sanctuary for the virus in the CNS and contribute
      to the development of acquired immunodeficiency syndrome dementia complex. This
      study evaluates a prodrug approach to improve the CNS delivery of the reverse
      transcriptase inhibitor 2',3'-dideoxyinosine (ddI) in combination with inhibition
      of P-glycoprotein-mediated efflux to increase the CNS delivery of the protease
      inhibitor nelfinavir and to determine whether any unanticipated drug interactions
      occur in this combination therapy. Three rats received either 6-chloro-2'3'
      dideoxypurine (6-Cl-ddP), a prodrug of ddI activated by adenosine deaminase,
      nelfinavir, nelfinavir and 6-Cl-ddP, nelfinavir and N-(4-[2-(1,2,3,4-tetrahydro
      6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4
      acridine carboxamide (GF120918) (a P-glycoprotein inhibitor), 6-Cl-ddP and
      GF120918, or 6-Cl-ddP, nelfinavir, and GF120918. Both 6-Cl-ddP and nelfinavir
      were administered as i.v. infusions, whereas GF120918 was given as an i.v. bolus
      2 h before sampling. Plasma and brain tissue concentrations of 6-Cl-ddP, ddI, and
      nelfinavir were determined. Neither nelfinavir nor GF120918 was shown to alter
      the brain/plasma ratios of 6-Cl-ddP or ddI. GF120918, however, increased the
      plasma concentrations of 6-Cl-ddP and ddI, resulting in increased brain
      concentrations. GF120918 increased the brain/plasma ratio of nelfinavir
      significantly (approximately 100-fold). The brain/plasma ratios of nelfinavir
      were reduced nearly 2-fold in rats treated with nelfinavir, 6-Cl-ddP, and
      GF120918 compared with rats receiving only nelfinavir and GF120918, suggesting a
      modest inhibition of nelfinavir uptake by 6-Cl-ddP. Overall, combined 6-Cl-ddP,
      nelfinavir, and GF120918 administration enhances the brain/plasma ratios of both
      ddI and nelfinavir.

PMID- 11950776
TI  - Current progress on esterases: from molecular structure to function.
AB  - This article reports on a symposium sponsored by the American Society for
      Pharmacology and Experimental Therapeutics and held at the April 2001
      Experimental Biology meeting. Current developments in molecular-based studies
      into the structure and function of cholinesterases, carboxylesterases, and
      paraoxonases are described. This article covers mechanisms of regulation of gene
      expression of the various esterases by developmental factors and xenobiotics, as
      well as the interplay between physiological and chemical regulation of enzyme
      activity.

PMID- 11950777
TI  - Structure-activity relationship in O-glucuronidation of indolocarbazole analogs.
AB  - The glucuronidation of 6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D
      glucopyranosyl)5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione (compound
      1), a potent inhibitor of DNA topoisomerase I, and its related indolocarbazole
      compounds was studied using human liver microsomes. Compound 1 and its
      structurally related compounds with the NHCHO moiety at the N-6 position were
      glucuronidated even if the positions of the phenolic hydroxy moiety were
      different in these molecules. Compounds that have the NHCH(CH(2)OH)(2) moiety at
      the N-6 position, however, were not glucuronidated. The three-dimensional
      structure of these substrates was determined by the semiempirical molecular
      orbitals calculation method. Computer-modeling studies, however, revealed that
      the O-glucuronidation of indolocarbazole analogs depended on the molecular size
      of the substrates. Compounds larger than 14.5 A in diameter perpendicular to the
      phenolic hydroxy moiety were not glucuronidated. The chemical reactivity of the
      hydroxy moiety, evaluated by the atom electron density and the electrostatic
      potential charges, was very similar in these substrates. These results suggest
      that a molecular length less than 14.5 A may be required for a substrate to
      interact with the active site of UDP-glucuronosyltransferase (UGT). To further
      characterize the glucuronidation of indolocarbazole analogs, compound 1 was used
      as a representative compound to assess expressed human UGTs. The glucuronidation
      of compound 1 was catalyzed by recombinant UGT1A9 and UGT1A10 among UGT isoforms
      tested.

PMID- 11950778
TI  - Carrier-mediated active transport of a novel thromboxane A(2) receptor antagonist
      [2-(4-chlorophenylsulfonylaminomethyl)indan-5-yl]acetate (Z-335) into rat liver.
AB  - To elucidate the transport system by which [2-(4
      chlorophenylsulfonylaminomethyl)indan-5-yl]acetate (Z-335) is taken up into the
      liver, we investigated the uptake characteristics of Z-335 in isolated rat
      hepatocytes. In addition, we estimated the hepatic uptake of Z-335 in intact rats
      under steady-state conditions and compared it with the in vitro uptake clearance.
      Uptake of Z-335 is highly concentrative (cell-to-medium concentration ratios were
      21.2 at 0.5 min and 71.7 at 5 min), temperature-dependent, and sensitive to
      metabolic inhibitors, indicating that uptake is mediated by energy-dependent
      uphill transport. In the presence of metabolic inhibitors [carbonyl cyanide p
      trifluoromethoxyphenylhydrazone and rotenone], uptake remained at 37 and 49% of
      the control value, respectively, suggesting that ATP-independent uptake
      contributes to the total uptake of Z-335. The concentration dependence of the
      initial uptake velocity indicated a two-component process, one saturable
      component, with a K(m) value of 45.6 microM and a V(max) value of 4.1 nmol/min/mg
      of protein, and a nonspecific diffusion clearance, with a P(dif) value of 8.3
      microl/min/mg of protein. The contribution of the carrier-mediated uptake to the
      total uptake in a linear range was estimated as 91%. The in vivo hepatic
      intrinsic clearance (CL(int, app)) was comparable with that in vitro uptake
      clearance (PS(influx)) and indicated that the CL(int, app) of Z-335 at steady
      state is rate-limited by the uptake process. In conclusion, hepatic intrinsic
      clearance of Z-335 at steady state is rate-limited by the uptake process since Z
      335 is efficiently taken up by an active transport mechanism, followed by
      metabolism or biliary excretion.

PMID- 11950779
TI  - Glucuronidation of statins in animals and humans: a novel mechanism of statin
      lactonization.
AB  - The active forms of all marketed hydroxymethylglutaryl (HMG)-CoA reductase
      inhibitors share a common dihydroxy heptanoic or heptenoic acid side chain. In
      this study, we present evidence for the formation of acyl glucuronide conjugates
      of the hydroxy acid forms of simvastatin (SVA), atorvastatin (AVA), and
      cerivastatin (CVA) in rat, dog, and human liver preparations in vitro and for the
      excretion of the acyl glucuronide of SVA in dog bile and urine. Upon incubation
      of each statin (SVA, CVA or AVA) with liver microsomal preparations supplemented
      with UDP-glucuronic acid, two major products were detected. Based on analysis by
      high-pressure liquid chromatography, UV spectroscopy, and/or liquid
      chromatography (LC)-mass spectrometry analysis, these metabolites were identified
      as a glucuronide conjugate of the hydroxy acid form of the statin and the
      corresponding delta-lactone. By means of an LC-NMR technique, the glucuronide
      structure was established to be a 1-O-acyl-beta-D-glucuronide conjugate of the
      statin acid. The formation of statin glucuronide and statin lactone in human
      liver microsomes exhibited modest intersubject variability (3- to 6-fold; n =
      10). Studies with expressed UDP glucuronosyltransferases (UGTs) revealed that
      both UGT1A1 and UGT1A3 were capable of forming the glucuronide conjugates and the
      corresponding lactones for all three statins. Kinetic studies of statin
      glucuronidation and lactonization in liver microsomes revealed marked species
      differences in intrinsic clearance (CL(int)) values for SVA (but not for AVA or
      CVA), with the highest CL(int) observed in dogs, followed by rats and humans. Of
      the statins studied, SVA underwent glucuronidation and lactonization in human
      liver microsomes, with the lowest CL(int) (0.4 microl/min/mg of protein for SVA
      versus approximately 3 microl/min/mg of protein for AVA and CVA). Consistent with
      the present in vitro findings, substantial levels of the glucuronide conjugate
      (approximately 20% of dose) and the lactone form of SVA [simvastatin (SV);
      approximately 10% of dose] were detected in bile following i.v. administration of
      [(14)C]SVA to dogs. The acyl glucuronide conjugate of SVA, upon isolation from an
      in vitro incubation, underwent spontaneous cyclization to SV. Since the rate of
      this lactonization was high under conditions of physiological pH, the present
      results suggest that the statin lactones detected previously in bile and/or
      plasma following administration of SVA to animals or of AVA or CVA to animals and
      humans, might originate, at least in part, from the corresponding acyl
      glucuronide conjugates. Thus, acyl glucuronide formation, which seems to be a
      common metabolic pathway for the hydroxy acid forms of statins, may play an
      important, albeit previously unrecognized, role in the conversion of active HMG
      CoA reductase inhibitors to their latent delta-lactone forms.

PMID- 11950781
TI  - 3-O-methyldobutamine, a major metabolite of dobutamine in humans.
AB  - Dobutamine is a synthetic ionotropic catecholamine commonly used to treat heart
      failure and shock. The catabolic fate of dobutamine in humans has yet to be
      reported, although formation of 3-O-methyldobutamine represents the principal
      pathway of dobutamine disposition in the dog. Herein, we describe the isolation
      and identification of 3-O-methyldobutamine in the urine of children receiving
      infusions of racemic dobutamine. In a 9-year-old child with heart failure
      approximately 80% of dobutamine administered intravenously at steady state was
      detected in the urine. Forty-seven percent of infused dobutamine was identified
      as 3-O-methyldobutamine and its acid-hydrolyzed derivatives, the latter mostly
      conjugated with sulfate (33%). Thirty-two percent consisted of acid-hydrolyzed
      dobutamine metabolites, primarily conjugated with sulfate (16%). Sonicates of
      human blood mononuclear cells catalyzed the formation of 3-O-methyldobutamine
      from dobutamine and S-adenosylmethionine in vitro. These findings indicate that
      formation of 3-O-methyldobutamine constitutes a major pathway of dobutamine
      metabolism in humans.

PMID- 11950780
TI  - Neotrofin is transported out of brain by a saturable mechanism: possible
      involvement of multidrug resistance and monocarboxylic acid transporters.
AB  - Neotrofin (AIT-082; leteprinim potassium) is transported out of brain by a
      saturable mechanism and in this study the mechanisms mediating this efflux were
      evaluated. Intracerebroventricular coadministration of [(14)C]Neotrofin with
      verapamil, a P-glycoprotein inhibitor, probenecid, an organic anion transporter
      inhibitor, 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2
      dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), a
      multidrug resistance-associated protein inhibitor, and salicylate or benzoate,
      both monocarboxylic acid transporter substrates, inhibited the efflux of
      [(14)C]Neotrofin. Additionally, Neotrofin inhibited the efflux of [(3)H]quinidine
      from brain. Compounds can diffuse from cerebrospinal fluid (CSF) into
      extracellular fluid of brain parenchyma and thus, efflux of [(14)C]Neotrofin
      after intracerebroventricular administration may indicate active transport across
      choroid plexus epithelium, brain capillary endothelium, or both. To determine
      whether [(14)C]Neotrofin efflux occurs at the brain capillary endothelium,
      experiments were performed in which [(14)C]Neotrofin was administered
      intraparenchymally. The t(1/2) for [(14)C]Neotrofin disappearance from brain
      after intraparenchymal administration was significantly lower than that for
      [(3)H]sucrose and the efflux of Neotrofin was inhibited by 600-fold excess of
      unlabeled Neotrofin, verapamil, MK571, and salicylate. Together, these data
      suggest that a saturable mechanism for the efflux of Neotrofin is located at the
      blood-brain barrier and possibly the blood-CSF barrier. It is likely that
      multiple transporters are involved in the efflux of Neotrofin and these may
      include multidrug resistance and monocarboxylic acid transporters. These data are
      discussed in detail with respect to the site of transporter expression, the
      recent identification of numerous multidrug resistance-associated protein and
      monocarboxylic acid transporter homologs, the existence of other potential brain
      efflux transporters, and the availability of specific pharmacological agents with
      which to distinguish these transporters.

PMID- 11950782
TI  - Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6:
      implications for cyclophosphamide metabolism.
AB  - Cytochrome P450 2B6 is a genetically polymorphic enzyme that is important in the
      metabolism of a number of clinically used drugs. This enzyme is not as well
      studied as other cytochrome P450 (P450) isoforms because of the lack of specific
      antibodies, probe drugs, and inhibitors. Although recent progress has been made
      toward specific antibodies and probe drugs, a specific enzyme inhibitor is still
      lacking. Studies suggest that CYP2B6 plays an important role in the 4
      hydroxylation of cyclophosphamide and that this reaction can be inhibited by
      triethylenethiophosphoramide (thioTEPA). We therefore wished to test the
      hypothesis that thioTEPA is an inhibitor of CYP2B6. Using human liver microsomes
      (HLMs) and recombinant P450 enzymes, we demonstrated that thioTEPA is a potent
      and specific inhibitor of CYP2B6. Enzyme activity was reduced 78.1 +/- 0.2% by 50
      microM thioTEPA when CYP2B6 activity was measured by following the metabolism of
      200 microM S-mephenytoin to nirvanol. thioTEPA did not significantly inhibit
      (<20% at 100 microM) the other isoforms tested (CYP1A2, CYP2C8, CYP2C9, CYP2C19,
      CYP2D6, CYP2E1, and CYP3A4). thioTEPA seems to be a potent noncompetitive
      inhibitor of CYP2B6, with K(i) values of 4.8 +/- 0.3 and 6.2 +/- 0.7 microM for
      HLMs and recombinant CYP2B6, respectively, values that are within the plasma
      concentration range of thioTEPA at therapeutic doses (1.1-18.6 microM). We
      conclude that thioTEPA is a potent and specific inhibitor of CYP2B6 and that this
      is the likely mechanism by which thioTEPA inhibits the activation of
      cyclophosphamide. Furthermore, thioTEPA may prove to be a valuable new tool for
      the study of this important drug-metabolizing enzyme.

PMID- 11950783
TI  - Glucuronidation of the dietary fatty acids, phytanic acid and docosahexaenoic
      acid, by human UDP-glucuronosyltransferases.
AB  - Linoleic acid has recently been shown to be glucuronidated in vitro by human
      liver and intestinal microsomes and recombinant UGT2B7. In the present study, the
      dietary fatty acids (FA), phytanic acid (PA), and docosahexaenoic acid (DHA) have
      been used as substrates for human UDP-glucuronosyltransferases (UGTs). Both
      compounds were effectively glucuronidated by human liver microsomes (HLM; 1.25 +/
      0.36 and 1.12 +/- 0.32 nmol/mg x min for PA and DHA, respectively) and UGT2B7
      (0.71 and 0.53 nmol/mg x min). Kinetic analysis produced relatively low K(m)
      values for PA with both HLM and UGT2B7 (149 and 108 microM, respectively). The
      K(m) for DHA glucuronidation by HLM (460 microM) was considerably higher than
      that for UGT2B7 (168 microM), suggesting the involvement in microsomes of other
      UGT isoforms in addition to UGT2B7. Glucuronidation of PA and DHA by
      gastrointestinal microsomes from 16 human subjects was determined. In general,
      both PA and DHA were glucuronidated by gastric and intestinal microsomes, and
      activity toward both substrates was lowest in the stomach, increased in the small
      intestine, and lower in the colon. However, there were large interindividual
      variations in UGT activity toward both substrates in all segments of the
      intestine, as has been seen with other substrates. Thus, PA and DHA are effective
      in vitro substrates for human liver, gastric and intestinal microsomes, and
      glucuronidation may play a role in modulating the availability of these FA as
      ligands for nuclear receptors.

PMID- 11950784
TI  - Effects of endogenous steroids on CYP3A4-mediated drug metabolism by human liver
      microsomes.
AB  - In the present study, we investigated the effects of 14 endogenous steroids on
      the CYP3A4-mediated drug metabolism by human liver microsomes in vitro.
      Nevirapine (NVP) 2-, 12-hydroxylations, carbamazepine (CBZ) 10,11-epoxidation,
      triazolam (TZM) 1'-, 4-hydroxylations, erythromycin (EM) N-demethylation, and 2
      sulphamoylacetylphenol (SMAP) formation from zonisamide (ZNS) were investigated.
      The activities of the NVP 2-, 12-hydroxylations, the CBZ 10,11-epoxidation, and
      the TZM 4-hydroxylation were activated by endogenous androgens, such as
      androstenedione (AND), testosterone, and dehydroepiandrosterone. However, these
      androgens inhibited EM N-demethylation, TZM 1'-hydroxylation, and SMAP formation.
      To understand the mechanisms of these effects of androgens on CYP3A4 activities,
      we performed a kinetic analysis of the metabolism of CBZ and ZNS in the presence
      or absence of AND using the modified two-site equation model. The addition of AND
      to the reaction mixture caused a drastic increase in the activity of CBZ 10,11
      epoxidase, especially at a low substrate concentration, and resulted in a change
      in the kinetics from the sigmoid to Michaelis-Menten type. On the other hand, the
      metabolism of ZNS was strongly inhibited by AND, although no allosteric change
      was observed in this case. These data demonstrate that endogenous steroids,
      especially androgens, strongly affect CYP3A4-mediated drug metabolism in vitro.
      The postulated mechanisms of the interactions between AND and CBZ or ZNS are
      discussed.

PMID- 11950785
TI  - Human and rodent carboxylesterases: immunorelatedness, overlapping substrate
      specificity, differential sensitivity to serine enzyme inhibitors, and tumor
      related expression.
AB  - Carboxylesterases hydrolyze numerous endogenous and foreign compounds with
      diverse structures. Humans and rodents express multiple forms of
      carboxylesterases, which share a high degree of sequence identity (approximately
      70%). Alignment analyses locate in carboxylesterases several functional subsites
      such the catalytic triad as seen in acetylcholinesterase. The aim of this study
      was to determine among human and rodent carboxylesterases the immunorelatedness,
      overlapping substrate specificity, differential sensitivity to serine enzyme
      inhibitors, tissue distribution, and tumor-related expression. Six antibodies
      against whole carboxylesterases or synthetic peptides were tested for their
      reactivity toward 11 human or rodent recombinant carboxylesterases. The
      antibodies against whole proteins generally exhibited a broader cross-reactivity
      than the anti-peptide antibodies. All carboxylesterases hydrolyzed para
      nitrophenylacetate and para-nitrophenylbutyrate. However, the relative activity
      varied markedly from enzyme to enzyme (>20-fold), and some carboxylesterases
      showed a clear substrate preference. Carboxylesterases with the same functional
      subsites had a similar profile on substrate specificity and sensitivity toward
      phenylmethylsulfonyl fluoride (PMSF) and paraoxon, suggesting that these subsites
      play determinant roles in the recognition of substrates and inhibitors. Among
      three human carboxylesterases, HCE-1 hydrolyzed both substrates to a similar
      extent, whereas HCE-2 and HCE-3 showed an opposite substrate preference. All
      three enzymes were inhibited by PMSF and paraoxon, but they showed a marked
      difference in relative sensitivities. Based on immunoblotting analyses, HCE-1 was
      present in all tissues examined, whereas HCE-2 and HCE-3 were expressed in a
      tissue-restricted pattern. Colon carcinomas expressed slightly higher levels of
      HCE-1 and HCE-2 than the adjacent normal tissues, whereas the opposite was true
      with HCE-3.

PMID- 11950787
TI  - The metabolism and excretion of galantamine in rats, dogs, and humans.
AB  - Galantamine is a competitive acetylcholine esterase inhibitor with a beneficial
      therapeutic effect in patients with Alzheimer's disease. The metabolism and
      excretion of orally administered (3)H-labeled galantamine was investigated in
      rats and dogs at a dose of 2.5 mg base-Eq/kg body weight and in humans at a dose
      of 4 mg base-Eq. Both poor and extensive metabolizers of CYP2D6 were included in
      the human study. Urine, feces, and plasma samples were collected for up to 96 h
      (rats) or 168 h (dogs and humans) after dosing. The radioactivity of the samples
      and the concentrations of galantamine and its major metabolites were analyzed. In
      all species, galantamine and its metabolites were predominantly excreted in the
      urine (from 60% in male rats to 93% in humans). Excretion of radioactivity was
      rapid and nearly complete at 96 h after dosing in all species. Major metabolic
      pathways were glucuronidation, O-demethylation, N-demethylation, N-oxidation, and
      epimerization. All metabolic pathways observed in humans occurred in at least one
      animal species. In extensive metabolizers for CYP2D6, urinary metabolites
      resulting from O-demethylation represented 33.2% of the dose compared with 5.2%
      in poor metabolizers, which showed correspondingly higher urinary excretion of
      unchanged galantamine and its N-oxide. The glucuronide of O-desmethyl-galantamine
      represented up to 19% of the plasma radioactivity in extensive metabolizers but
      could not be detected in poor metabolizers. Nonvolatile radioactivity and
      unchanged galantamine plasma kinetics were similar for poor and extensive
      metabolizers. Genetic polymorphism in the expression of CYP2D6 is not expected to
      affect the pharmacodynamics of galantamine.

PMID- 11950786
TI  - Expression of the rat CYP2A3 gene in transgenic mice.
AB  - Rat CYP2A3 and mouse CYP2A5 are predominantly expressed in the olfactory mucosa.
      CYP2A3 is also expressed in the lung at a low level, whereas CYP2A5 is expressed
      in several additional tissues. To better understand the transcriptional
      regulation of the CYP2A genes, transgenic mice were generated with a full-length
      CYP2A3 gene fragment containing 3.4 kilobases of the 5'-flanking region. CYP2A3
      mRNA was detected in the brain and olfactory bulb in four transgenic mouse lines,
      in the olfactory mucosa in three lines, and in kidney, liver, lung, and small
      intestine in two lines. Thus, the expression of the CYP2A3 transgene mimicked the
      tissue distribution pattern of mouse CYP2A5 rather than that of rat CYP2A3.
      Furthermore, the levels of CYP2A3 mRNA were very low in all lines examined,
      suggesting that more distal regulatory regions may be involved in the abundant
      expression of the CYP2A genes in the olfactory mucosa.

PMID- 11950788
TI  - Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural
      requirements.
AB  - Recent studies in our laboratory in the human hepatic and intestinal cell lines
      Hep G2 and Caco-2 have demonstrated induction of UGT1A1 by the flavonoid chrysin
      (5,7-dihydroxyflavone) using catalytic activity assays and Western and Northern
      blotting. In the present study, we examined which features of the flavonoid
      structures were associated with induction of UGT1A1 and whether common drug
      metabolizing enzyme inducers also produce this induction. We also determined
      whether flavonoid treatment affected sulfate conjugation and CYP1A1 activity. We
      used intact Hep G2 cells for these studies, with chrysin as the model substrate.
      Both glucuronidation and sulfation were measured. Hep G2 cells were pretreated
      for 3 days with 25 microM concentrations of 22 flavonoids (n = 4-12). Only four
      flavonoids demonstrated induction of glucuronidation similar to that of chrysin
      (i.e., 3-5-fold in the intact cells). These were acacetin, apigenin, luteolin,
      and diosmetin, all of which, like chrysin, are 5,7-dihydroxyflavones with varying
      substituents in the B-ring. 5-Hydroxy-7-methoxyflavone and 5-methyl-7
      hydroxyflavone produced a modest 1.5 to 2-fold induction, whereas all other
      flavonoids examined were without effect. None of the flavonoids caused more than
      a modest change in sulfation activity (60-140% of control). In contrast, all
      tested 5,7-dihydroxyflavones and -flavonols induced CYP1A1 activity
      (ethoxyresorufin deethylation). Of seven common drug-metabolizing enzyme inducers
      only 3-methylcholanthrene and oltipraz showed modest induction of chrysin
      glucuronidation but not 2,3,7,8-tetrachlorodibenzo-p-dioxin or phenobarbital.
      Together, these results strongly suggest that the flavonoid induction of UGT1A1
      is through a novel nonaryl hydrocarbon receptor-mediated mechanism.

PMID- 11950790
TI  - Glucuronidation versus oxidation of the flavonoid galangin by human liver
      microsomes and hepatocytes.
AB  - In a previous study, we used human liver microsomes for the first time to study
      cytochrome P450 (P450)-mediated oxidation of the flavonoid galangin. The
      combination of CYP1A2 and CYP2C9 produced a V(max)/K(m) value of 13.6 +/- 1.1
      microl/min/mg of protein. In the present extended study, we determined
      glucuronidation rates for galangin with the same microsomes. Two major and one
      minor glucuronide were identified by liquid chromatography/mass spectrometry. The
      V(max)/K(m) values for the two major glucuronides conjugated in the 7- and 3
      positions were 155 +/- 30 and 427 +/- 26 microl/min/mg of protein, thus,
      exceeding that of oxidation by 11 and 31 times, respectively. This highly
      efficient glucuronidation appeared to be catalyzed mainly by the UDP
      glucuronosyltransferase (UGT)1A9 isoform but also by UGT1A1 and UGT2B15.
      Sulfation of galangin by the human liver cytosol, mediated mainly but not
      exclusively by sulfotransferase (SULT) 1A1, also appeared to be efficient. These
      conclusions were strongly supported by experiments using the S9 fraction of the
      human liver, in which all three metabolic pathways could be directly compared.
      When galangin metabolism was examined in fresh plated hepatocytes from six
      donors, glucuronidation clearly predominated followed by sulfation. Oxidation
      occurred only to a minor extent in two of the donors. This study for the first
      time establishes that glucuronidation and sulfation of galangin, and maybe other
      flavonoids, are more efficient than P450-mediated oxidation, clearly being the
      metabolic pathways of choice in intact cells and therefore likely also in vivo.

PMID- 11950792
TI  - Intestinal metabolism: the role of enzyme localization in phenol metabolite
      kinetics.
AB  - The influence of enzyme localization and blood flow on intestinal elimination was
      evaluated in rats. Phenol was administered vascularly (approximately 1400 and
      2500 microg) and luminally (intrajejunal bolus doses of approximately 100 and
      1000 microg) to the recirculating in situ perfused intestine. The portal effluent
      and the reservoir were sampled. The intestinal extraction ratios for phenol at
      the low and high vascular doses were (mean +/- S.D., n = 3) 0.09 +/- 0.02 and
      0.11 +/- 0.01, respectively. The perfusion flow rate was also varied from 5 to 12
      ml/min at a vascular dose of approximately 2500 microg of phenol. The organ
      clearance at the lowest flow rate significantly exceeded those at the higher flow
      rates. The presence of a diffusional barrier at the mucosa-serosa interface was
      suggested. The calculated mean diffusional clearance of phenol was 1.11 ml/min.
      Sulfation was the predominant metabolic pathway after vascular administration of
      phenol. After luminal dosing, the intestinal intrinsic clearances of phenol at
      the low and high doses were 7.29 +/- 1.39 (n = 4) and 3.55 +/- 1.16 ml/min (n =
      3), respectively, indicating saturation at the higher dose. Moreover, there was a
      decrease in the area under the curve ratio (metabolite/phenol) at the high
      luminal dose. Luminal administration, in general, produced greater
      glucuronidation. These data and STELLA simulations suggest that enzyme
      localization at both the cellular and tissue levels has a significant influence
      on intestinal metabolism.

PMID- 11950789
TI  - Induction of CYP3A expression by dehydroepiandrosterone: involvement of the
      pregnane X receptor.
AB  - Dehydroepiandrosterone (DHEA) is a steroid produced by the human adrenal gland.
      Administration of pharmacological doses of DHEA to rats changes expression of
      many genes, including the cytochrome P450 family members CYP4A1 and CYP3A23. It
      is known that induction of CYP4A expression by DHEA requires the peroxisome
      proliferator-activated receptor alpha (PPAR(alpha)). In the current study,
      PPAR(alpha)-null mice were used to examine the role of PPAR(alpha) in expression
      of CYP3A. In wild-type mice, 150 mg/kg DHEA-sulfate induced Cyp4a and Cyp3a11
      mRNAs by 5- and 2-fold, respectively. Induction of Cyp4a expression by DHEA
      sulfate was not observed in PPAR(alpha)-null mice, whereas induction of Cyp3a11
      expression by DHEA-sulfate was similar between genotypes. This suggests that
      PPAR(alpha) is not involved in induction of Cyp3a11 expression by DHEA. Because
      expression of CYP3A family members can be induced by activation of another member
      of the nuclear receptor superfamily, the pregnane X receptor (PXR), we examined
      the ability of DHEA to activate PXR. In transient transfection assays, DHEA and
      its metabolites androst-5-ene-3beta,17beta-diol (ADIOL), androst-5-ene-3,17
      dione, and androst-4-ene-3,17-dione were activators of PXR. Maximal induction of
      a PXR-responsive reporter gene of approximately 3-fold was observed at
      concentrations of 50 to 100 microM, indicating that these steroids are relatively
      weak activators of PXR. Human and murine PXR exhibited different specificities
      for DHEA and its metabolites. ADIOL activated reporter gene expression in the
      presence of murine but not human PXR. Results of these studies suggest that the
      induction of rodent CYP3A expression upon treatment with high doses of DHEA
      occurs through activation of PXR.

PMID- 11950791
TI  - Sulfation of budesonide by human cytosolic sulfotransferase,
      dehydroepiandrosterone-sulfotransferase (DHEA-ST).
AB  - Budesonide, a synthetic glucocorticosteroid, is used in the treatment of asthma
      and allergic reactions, rhinitis, and inflammatory bowel disease. It is
      distributed as a mixture of two epimers, 22R and 22S, and has a high ratio of
      topical to systemic activity due to extensive first-pass metabolism to
      metabolites with minimal activity. Previous studies have shown that the epimers
      are metabolized by the cytochrome P450 monooxygenase system. Metabolism and
      inactivation of the epimers by the phase II enzymes has not been well
      characterized. This study describes the conjugation of budesonide by human
      cytosolic sulfotransferases (SULTs). Seven human SULTs were analyzed to determine
      which were capable of catalyzing the sulfation of the epimers of budesonide. Only
      dehydroepiandrosterone-sulfotransferase (DHEA-ST, SULT2A1) was capable of forming
      a sulfated budesonide product. The epimeric forms of budesonide display different
      kinetic activities with the 22R epimer having a 3.5-fold greater rate of
      sulfation activity than the 22S epimer. The structure of budesonide shows two
      hydroxyl sites that are potential sites for sulfate conjugation, but analysis by
      mass spectrometry indicates the formation of only a monosulfated budesonide
      product. A modeling approach was used to define the site of sulfation as that of
      the 21-hydroxyl group. Although sulfation of budesonide by DHEA-ST may not be an
      important factor in its use as an antiasthmatic, intestinal and hepatic sulfation
      will be important for its proposed systemic use as an anti-inflammatory agent.

PMID- 11950793
TI  - Characterization of cytochrome P450 2D6.1 (CYP2D6.1), CYP2D6.2, and CYP2D6.17
      activities toward model CYP2D6 substrates dextromethorphan, bufuralol, and
      debrisoquine.
AB  - Over 50 allelic variants of cytochrome P450 2D6 (CYP2D6) encoding fully
      functional, reduced-activity, or nonfunctional proteins have been described.
      Compared with Caucasians, studies in black populations demonstrate a tendency
      toward slower CYP2D6 activity, attributed in part to the presence of a variant
      allele associated with reduced activity, the CYP2D6*17 allele. To investigate the
      kinetic characteristics of this variant protein, expression constructs coding for
      CYP2D6.1, CYP2D6.2, and CYP2D6.17 gene products were prepared and transfected
      into mammalian COS-7 and insect (Trichoplusia ni) cells for expression.
      Microsomal fractions containing the expressed proteins were used to determine the
      kinetic parameters K(m), V(max), and intrinsic clearance (Cl(int)) for the model
      substrates dextromethorphan, bufuralol, and debrisoquine. Relative to the wild
      type CYP2D6.1 protein expressed in COS-7 cells, CYP2D6.17 exhibited a 2-fold
      higher K(m) and a 50% reduction in V(max) using dextromethorphan as the
      substrate. In contrast, no appreciable change in bufuralol K(m) was observed with
      CYP2D6.17 whereas V(max) was decreased by 50%. When expressed in the baculovirus
      expression system, CYP2D6.17 exhibited a 6-fold increase in K(m) but no change in
      V(max) with dextromethorphan as the substrate, a 2-fold higher K(m) and 50%
      reduction in V(max) with bufuralol, and a 3-fold increase in K(m) and no change
      in V(max) with debrisoquine relative to CYP2D6.1. These data indicate that
      CYP2D6.17 exhibits reduced metabolic activity toward all three commonly used
      CYP2D6 substrates, although specific effects on substrate affinity and turnover
      demonstrate some substrate dependence.

PMID- 11950794
TI  - Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols
      by CYP2C9 and CYP2C19 in human liver microsomes.
AB  - Limonene, a monocyclic monoterpene, is present in orange peel and other plants
      and has been shown to have chemopreventive activities. (+)- and (-)-Limonene
      enantiomers were incubated with human liver microsomes and the oxidative
      metabolites thus formed were analyzed using gas chromatography-mass spectrometry.
      Two kinds of metabolites, (+)- and (-)-trans-carveol (a product by 6
      hydroxylation) and (+)- and (-)-perillyl alcohol (a product by 7-hydroxylation),
      were identified, and the latter metabolites were found to be formed more
      extensively, the former ones with liver microsomes prepared from different human
      samples. Sulfaphenazole, flavoxamine, and antibodies raised against purified
      liver cytochrome P450 (P450) 2C9 that inhibit both CYP2C9- and 2C19-dependent
      activities, significantly inhibited microsomal oxidations of (+)- and (-)
      limonene enantiomers. The limonene oxidation activities correlated well with
      contents of CYP2C9 and activities of tolbutamide methyl hydroxylation in liver
      microsomes of 62 human samples, whereas these activities did not correlate with
      contents of CYP2C19 and activities of S-mephenytoin 4-hydroxylation. Of 11
      recombinant human P450 enzymes (expressed in Trichoplusia ni cells) tested,
      CYP2C8, 2C9, 2C18, 2C19, and CYP3A4 catalyzed oxidations of (+)- and (-)
      limonenes to respective carveols and perillyl alcohol. Interestingly, human
      CYP2B6 did not catalyze limonene oxidations, whereas rat CYP2B1 had high
      activities in catalyzing limonene oxidations. These results suggest that both (+)
      and (-)-limonene enantiomers are oxidized at 6- and 7-positions by CYP2C9 and
      CYP2C19 in human liver microsomes. CYP2C9 may be more important than CYP2C19 in
      catalyzing limonene oxidations in human liver microsomes, since levels of the
      former protein are more abundant than CYP2C19 in these human samples. Species
      related differences exist in the oxidations of limonenes in CYP2B subfamily in
      rats and humans.

PMID- 11950795
TI  - Induction of cytochrome P450 3A4 in primary human hepatocytes and activation of
      the human pregnane X receptor by tamoxifen and 4-hydroxytamoxifen.
AB  - Tamoxifen is a widely utilized antiestrogen in the treatment and chemoprevention
      of breast cancer. Clinical studies document that tamoxifen administration
      markedly enhances the systemic elimination of other drugs. Additionally,
      tamoxifen enhances its own clearance following repeated dosing. The mechanisms
      that underlie these clinically important events remain unresolved. Here, we
      report that tamoxifen and its metabolite 4-hydroxytamoxifen markedly induce
      cytochrome P450 3A4, a drug-metabolizing enzyme of central importance, in primary
      cultures of human hepatocytes. Tamoxifen and 4-hydroxytamoxifen (1-10 microM)
      significantly increased the CYP3A4 expression and activity (measured as the rate
      of testosterone 6beta-hydroxylation). Maximal induction was achieved at the 5
      microM level. At this level, tamoxifen and 4-hydroxytamoxifen caused a 1.5- to
      3.3-fold (mean, 2.1-fold) and 3.4- to 17-fold (mean, 7.5-fold) increase in the
      CYP3A4 activity, respectively. In comparison, rifampicin treatment resulted in a
      6- to 16-fold (mean, 10.5-fold) increase. We also observed corresponding increase
      in the CYP3A4 immunoreactive protein and mRNA levels. Furthermore, tamoxifen and
      4-hydroxytamoxifen efficaciously activated the human pregnane X receptor (hPXR;
      also known as the steroid xenobiotic receptor), a key regulator of CYP3A4
      expression. The efficacy of tamoxifen and 4-hydroxytamoxifen relative to
      rifampicin for hPXR activation was approximately 30 and 60%, respectively. Our
      results indicate that the mechanism of tamoxifen-mediated alteration in drug
      clearance pathways in humans may involve CYP3A4 induction by the parent drug
      and/or its metabolite. Furthermore, the CYP3A4 induction may be a result of hPXR
      activation. These findings have important implications for optimizing the use of
      tamoxifen and in the development of newer antiestrogens.

PMID- 11950797
TI  - Non-alcoholic steatohepatitis (NASH): where are we now and where are we going?
AB  - Although non-alcoholic steatohepatitis (NASH) was considered relatively uncommon
      prior to the middle of the last decade, over the past three years there has been
      an explosion of studies on various aspects of NASH with one study reporting that
      after hepatitis C, NASH was the most common diagnosis in patients presenting
      largely with persistent abnormalities of liver function tests. The field of NASH
      has come a long way in a relatively short space of time. This article considers
      advances in knowledge that have arisen as a result of these studies and
      highlights areas for further work.

PMID- 11950798
TI  - Aspirin injury and H pylori.

PMID- 11950799
TI  - The SPINK in chronic pancreatitis: similar finds, different minds.

PMID- 11950800
TI  - Should abnormal oesophageal motility in gastro-oesophageal reflux disease (GORD)
      influence decisions about fundoplication?

PMID- 11950801
TI  - Helicobacter pylori infection potentiates aspirin induced gastric mucosal injury
      in Mongolian gerbils.
AB  - BACKGROUND: Helicobacter pylori infection and non-steroidal anti-inflammatory
      drugs are two major causes of gastric ulceration but interactions between H
      pylori and these drugs in gastric mucosal injury are unclear. AIMS: We studied
      the influence of experimental H pylori infection on gastric mucosal injury
      induced by aspirin. SUBJECTS: Male Mongolian gerbils free of specific pathogens
      were used. METHODS: H pylori ATCC43504 culture broth was administered by oral
      gavage at seven weeks of age. After three weeks, acidified aspirin (400 mg/kg)
      was administered orally, and three hours later the total area of gastric
      erosions, myeloperoxidase (MPO) activity (an index of neutrophil accumulation),
      thiobarbituric acid reactive substances (TBARS, an index of lipid peroxidation),
      and KC/GRO (a chemoattractive cytokine in rodents) were measured in gastric
      mucosa. To determine the role of neutrophils in these circumstances, antigerbil
      neutrophil rabbit serum (ANS) was administered to some animals 18 hours before
      aspirin. RESULTS: Aspirin caused more extensive haemorrhagic erosions (33.1
      (12.3) mm2) associated with greater MPO activity (1887.7 (598.5) microU/mg
      protein) and TBARS (0.33 (0.14) nmol/mg protein) and KC/GRO concentrations (28.3
      (9.5) pg/mg protein) in infected than in uninfected gerbils (13.7 (2.3); 204.0
      (68.9); 0.12 (0.06); 3.1 (0.8), respectively) Pretreatment with ANS inhibited the
      increases in gastric erosions, MPO activity, and TBARS but not KC/GRO
      concentration. The reduction in aspirin induced mucosal injury by administration
      of ANS was much greater in H pylori infected animals (65%) than in uninfected
      animals (31%). CONCLUSIONS: H pylori infection potentiates aspirin induced
      gastric mucosal injury by mechanisms that include accumulation of activated
      neutrophils.

PMID- 11950803
TI  - NORCCAP (Norwegian colorectal cancer prevention): a randomised trial to assess
      the safety and efficacy of carbon dioxide versus air insufflation in colonoscopy.
AB  - BACKGROUND: To eliminate the risk of combustion during electrosurgical procedures
      and to reduce patient discomfort, carbon dioxide (CO2) insufflation has been
      recommended during colonoscopy. However, air insufflation is still the standard
      method, perhaps due to the lack of suitable equipment and shortage of randomised
      studies. AIMS: This randomised controlled trial was conducted to assess patient
      tolerance and safety when using CO2 insufflation during colonoscopy. PATIENTS:
      Over an eight month period a successive series of patients referred for a
      baseline colonoscopy due to findings in a flexible sigmoidoscopy screening trial
      were randomly assigned to the use of either air or CO2 insufflation during
      colonoscopy. METHODS: End tidal CO2 (ETCO2), a non-invasive parameter of arterial
      pCO2, was registered before and repeatedly during and after the examination. The
      patient's experience of pain during and after the examination was registered
      using a visual analogue scale (VAS). Sedation was not used routinely. RESULTS:
      CO2 insufflation was used in 121 patients (51%) and air in 119 patients (49%).
      The groups were similar in age, sex, and caecal intubation rate. No rise in ETCO2
      was registered. There were statistically significant differences in VAS scores
      between the groups with less pain reported when using CO2. CONCLUSIONS: This
      randomised study of unsedated patients shows that CO2 insufflation is safe during
      colonoscopy with no rise in ETCO2 level. CO2 was found to be superior to air in
      terms of pain experienced after the examination.

PMID- 11950802
TI  - You get what you expect? A critical appraisal of imaging methodology in
      endosonographic cancer staging.
AB  - BACKGROUND AND AIMS: After an initial period of excellent results with newly
      introduced imaging procedures, the accuracy of most imaging methods declines in
      later publications. This effect may be due to various methodological factors
      involved in the research. Using the example of endoscopic ultrasound (EUS), this
      study aimed to elucidate one of the factors possibly concerned--namely, the
      extent to which the examiners are adequately blinded. METHODS: Well documented
      videotapes of EUS examinations of 101 patients with resected tumours of the
      oesophagus (n=32), stomach (n=33), or pancreas (n=36) were evaluated in three
      different ways: firstly, retrospective analysis under routine clinical
      conditions; secondly, evaluation of EUS videotapes in a strictly blinded fashion;
      and thirdly, evaluation of the same videotapes but with additional information
      from the video endoscopic appearance (oesophageal/gastric cancer) or from
      computed tomography results (pancreatic cancer). Histopathological T staging was
      used as the reference method. RESULTS: The accuracy of EUS in T staging was 73%
      under routine conditions. This value fell significantly to 53% for the blinded
      evaluation but increased again to 62% for the unblinded evaluation. The
      sensitivity of staging T1/T2 tumours was 72% (routine EUS), 59% (blinded EUS),
      and 70% (unblinded EUS). The respective values for advanced tumours were 85%,
      74%, and 72%. CONCLUSIONS: The accuracy of EUS for T staging in clinical practice
      appears to be lower than has previously been reported. In addition, blinded
      analysis produced significantly poorer results, which improved when another test
      was added. It may be speculated that better results with routine EUS obtained in
      a clinical setting are due to additional sources of information.

PMID- 11950804
TI  - Lack of simian immunodeficiency virus (SIV) specific IgA response in the
      intestine of SIV infected rhesus macaques.
AB  - BACKGROUND: Little is known about secretory immunity-the major defence mechanism
      at mucosal surfaces-in human immunodeficiency virus (HIV) infected patients,
      especially in the early stages of the disease. AIMS: The aim of the study was to
      analyse mucosal immunoglobulin production and simian immunodeficiency virus (SIV)
      specific antibody response in the intestinal mucosa during the course of SIV
      infection in comparison with serum and saliva. ANIMALS AND METHODS: IgG, IgA, and
      IgM concentrations were determined in supernatants of short term cultured
      duodenal biopsies, serum, and saliva from SIV infected rhesus macaques (n=8) and
      controls (n=2) by ELISA at defined times before and after infection. Specific
      antibodies to SIV were detected by western blot and/or dot blot analysis. In
      addition, rectal swabs from two uninfected and 12 SIV infected rhesus macaques
      (seven without and five with enteritis) were analysed for albumin and IgG
      concentrations. RESULTS: An increase in total intestinal IgG and a decrease in
      IgA were observed. SIV specific IgG or IgA responses were detectable as early as
      one week after SIV infection in the serum of seven of eight animals. In contrast,
      intestinal SIV specific IgG production was detected only four weeks after
      infection in six of eight animals, and intestinal SIV specific IgA was not
      produced in the intestine at any time point. In saliva, the secretory component
      on SIV specific IgA was only detected in one animal at week 24 after infection.
      Enteritis is frequent in SIV infected animals and results in a significant
      increase in albumin and IgG secretion into the intestinal lumen. CONCLUSION:
      Despite modest quantitative changes in mucosal immunglobulin production there was
      a total lack of SIV specific IgA synthesis in the intestine during SIV infection.
      This lack or disturbed secretory SIV specific IgA response at mucosal surfaces
      may explain the rapid and high HIV/SIV replication in this compartment. In
      addition, our investigations indicate secretion of serum proteins into intestinal
      fluids during SIV infection. Previous investigations using intestinal secretions
      or swabs for analysing quantitative and specific immunglobulins therefore should
      be interpreted with caution.

PMID- 11950806
TI  - The first large population based twin study of coeliac disease.
AB  - BACKGROUND AND AIMS: The genetic load in coeliac disease has hitherto been
      inferred from case series or anecdotally referred twin pairs. We have evaluated
      the genetic component in coeliac disease by estimating the concordance rate for
      the disease among twin pairs in a large population based study. METHODS: The
      Italian Twin Registry was matched with the membership lists of a patient support
      group. Forty seven twin pairs were recruited and screened for antiendomysial
      (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was
      verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and
      DQB1 molecules. RESULTS: Concordance rates for coeliac disease differ
      significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and
      dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest
      concordance so far reported for a multifactorial disease. A logistic regression
      model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity,
      showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for
      heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of
      contracting the disease of 3.3 and 1.4, respectively. The risk of being
      concordant for coeliac disease estimated for the non-index twin of MZ pairs was
      17 (95% confidence interval 2.1-134), independent of the DQ at risk genotype.
      CONCLUSION: This study provides substantial evidence for a very strong genetic
      component in coeliac disease, which is only partially due to the HLA region.

PMID- 11950805
TI  - Recovery of ischaemic injured porcine ileum: evidence for a contributory role of
      COX-1 and COX-2.
AB  - BACKGROUND: We have previously shown that the non-selective cyclooxygenase (COX)
      inhibitor indomethacin retards recovery of intestinal barrier function in
      ischaemic injured porcine ileum. However, the relative role of COX-1 and COX-2
      elaborated prostaglandins in this process is unclear. AIMS: To assess the role of
      COX-1 and COX-2 elaborated prostaglandins in the recovery of intestinal barrier
      function by evaluating the effects of selective COX-1 and COX-2 inhibitors on
      mucosal recovery and eicosanoid production. METHODS: Porcine ileal mucosa
      subjected to 45 minutes of ischaemia was mounted in Ussing chambers, and
      transepithelial electrical resistance was used as an indicator of mucosal
      recovery. Prostaglandins E1 and E2 (PGE) and 6-keto-PGF1alpha (the stable
      metabolite of prostaglandin I2 (PGI2)) were measured using ELISA. Thromboxane B2
      (TXB2, the stable metabolite of TXA2) was measured as a likely indicator of COX-1
      activity. RESULTS: Ischaemic injured tissues recovered to control levels of
      resistance within three hours whereas tissues treated with indomethacin (5x10(-6)
      M) failed to fully recover, associated with inhibition of eicosanoid production.
      Injured tissues treated with the selective COX-1 inhibitor SC-560 (5x10(-6) M) or
      the COX-2 inhibitor NS-398 (5x10(-6) M) recovered to control levels of resistance
      within three hours, associated with significant elevations of PGE and 6-keto
      PGF1alpha compared with untreated tissues. However, SC-560 significantly
      inhibited TXB2 production whereas NS-398 had no effect on this eicosanoid,
      indicating differential actions of these inhibitors related to their COX
      selectivity. CONCLUSIONS: The results suggest that recovery of resistance is
      triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2.

PMID- 11950807
TI  - Neutrophil migration into indomethacin induced rat small intestinal injury is
      CD11a/CD18 and CD11b/CD18 co-dependent.
AB  - BACKGROUND: Neutrophils may exacerbate intestinal inflammatory diseases through
      secretion of proteolytic enzymes and reactive oxygen and nitrogen intermediates.
      AIMS: To define the mechanisms involved in neutrophil infiltration into the non
      steroidal anti-inflammatory disease inflamed intestine to develop strategies to
      regulate this process. METHODS: The small intestinal epithelium of (15 mg/kg)
      indomethacin treated rats was examined for cytokine mRNA. The kinetics of
      neutrophil accumulation into the gastrointestinal tract (including lumen
      contents) of inflamed rats was determined using radiolabelled (111In) neutrophils
      injected intravenously followed by a three hour migration period. To determine
      which adhesion molecules were critical for migration, rats were also injected
      with function blocking monoclonal antibodies to the beta2 (CD11/CD18) integrins.
      RESULTS: Interleukin 1beta, interleukin 1 receptor II, tumour necrosis factor
      alpha, and monocyte inflammatory peptide 2 but not monocyte chemoattractant
      protein 1 mRNA were detected in the epithelium within hours of indomethacin
      injection. Neutrophils were detectable in the small intestine and intestinal
      lumen by six hours and continued to accumulate until 48 hours post indomethacin
      injection. Neutrophil accumulation in the intestine was essentially blocked by
      anti-CD18, and partially blocked by either anti-CD11a or CD11b antibody
      treatment. Migration into the intestinal lumen was reduced by anti-CD11b.
      CONCLUSIONS: The small intestinal epithelium acts as one source of cytokines with
      properties important in the recruitment of neutrophils. In turn, neutrophil
      migration into the indomethacin inflamed small intestine is mediated by
      CD11a/CD18 and CD11b/CD18.

PMID- 11950808
TI  - Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of
      a 10 year prospective study.
AB  - BACKGROUND: Duodenal cancer is one of the leading causes of death in familial
      adenomatous polyposis (FAP) patients. An endoscopic surveillance programme was
      therefore initiated in 1988, the outcome of which is described in this paper.
      METHODS: We report the 10 year follow up of 114 patients with FAP who were
      prospectively screened for the presence and severity of duodenal adenomas.
      RESULTS: Six of 114 patients (median age 67 years) developed duodenal
      adenocarcinoma. Four of these were from 11 patients who originally had Spigelman
      stage IV disease (advanced duodenal polyposis), which gives a 36% risk within
      this group of developing cancer. One case of duodenal cancer arose from 41
      patients who originally had stage III disease (2%) and one cancer arose from 44
      patients with original stage II disease (2%). All six patients have died: five
      were inoperable and one had recurrence three years after a
      pancreaticoduodenectomy. There was no association between duodenal cancer and
      site of germline mutation of the APC gene. CONCLUSIONS: Surveillance for duodenal
      adenocarcinoma and subsequent early referral for curative surgery has not been
      effective. Selection of patients with advanced but benign (Spigelman stage IV)
      duodenal polyposis for prophylactic pancreaticoduodenectomy should therefore be
      considered and can now be justified on the basis of these results. More
      comprehensive endoscopic surveillance of high risk (stage III and IV) patients is
      needed in an attempt to avoid underestimating the severity of duodenal polyposis,
      and to evaluate the role of endoscopic therapy in preventing advanced disease.

PMID- 11950809
TI  - Plasma insulin-like growth factor 1, insulin-like growth factor binding protein
      3, and risk of colorectal cancer: a prospective study in northern Sweden.
AB  - BACKGROUND: Insulin-like growth factor 1 (IGF-1) has antiapoptotic and mitogenic
      effects on various cell types, and raised IGF-1 levels are increasingly being
      implicated as potential risk factors for cancer. AIMS: To examine the
      relationship between IGF-1 and its major plasma binding protein, IGF binding
      protein 3 (IGFBP-3), and the risk of colorectal cancer. METHODS: We conducted a
      case-control study nested within the Northern Sweden Health and Disease Cohort.
      IGF-1 and IGFBP-3 were measured in prediagnostic plasma samples from 168 men and
      women who developed cancers of the colon (n=110) or rectum (n=58), and from 336
      matched controls. RESULTS: Conditional logistic regression analyses showed an
      increase in colon cancer risk with increasing levels of IGF-1 (odds ratios (ORs)
      1.00, 1.89, 2.30, 2.66; p(trend)=0.03) and IGFBP-3 (ORs 1.00, 0.91, 1.80, 1.93;
      p(trend)=0.02). Rectal cancer risk was inversely related to levels of IGF-1 (ORs
      1.00, 0.45, 0.33, 0.33; p(trend)=0.09) and IGFBP-3 (ORs 1.00, 0.75, 0.66, 0.49;
      p(trend)=0.21). Mutual adjustments between IGF-1 and IGFBP-3 did not materially
      alter these relationships. CONCLUSIONS: These results support earlier findings of
      increased risk of colon cancer in subjects with elevated plasma IGF-1. Our
      results however do not support the hypothesis that the risk of rectal cancer
      could also be directly related to IGF-1 levels.

PMID- 11950810
TI  - The risk of subsequent primary cancers after colorectal cancer in southeast
      England.
AB  - BACKGROUND: Multiple cancers may occur in an individual because of a genetic
      predisposition, environmental exposure, cancer therapy, or immunological
      deficiency. Colorectal cancer is one of the most commonly diagnosed cancers, and
      inherited factors play an important role in its aetiology. AIMS: To characterise
      the occurrence of multiple primary cancers in patients diagnosed with colorectal
      cancer and explore the possibility of a common aetiology for different cancer
      sites. PATIENTS: The Thames Cancer Registry database was used to identify
      patients with a first colorectal cancer, resident in the North or South Thames
      region, diagnosed between 1 January 1961 and 31 December 1995. A total of 127 281
      patients were included, 61 433 men and 65 848 women. METHODS: Observed numbers of
      cancers occurring after the diagnosis of colorectal cancer were compared with
      expected numbers, calculated using appropriate age, sex, and period specific
      rates, to obtain standardised incidence ratios. The occurrence of colorectal
      cancers subsequent to cancers at other sites was also examined. RESULTS: Small
      intestinal cancer was significantly increased in men diagnosed with colorectal
      cancer before the age of 60 years and in women diagnosed with colorectal cancer
      after the age of 65 years. Colorectal cancer was also significantly increased
      after a first diagnosis of cancer of the small intestine. Other cancer sites with
      a significant increase after colorectal cancer included the cervix uteri, corpus
      uteri, and ovary. CONCLUSIONS: Patients with colorectal cancer are at increased
      risk of developing cancer at a number of other sites. Some of these associations
      are consistent with the effects of known inherited cancer susceptibility genes.

PMID- 11950811
TI  - Family history of cancer and germline BRCA2 mutations in sporadic exocrine
      pancreatic cancer.
AB  - BACKGROUND: Hereditary factors have been reported in 5-10% of cases with exocrine
      pancreatic cancer and recent data support a role for BRCA2. AIMS: We have studied
      the prevalence of germline BRCA2 mutations in two groups of patients with
      exocrine pancreatic cancer from an unselected series in Spain: group A included
      24 cases showing familial aggregation of cancer and group B included 54 age, sex,
      and hospital matched cases without such evidence. METHODS: Information was
      obtained by interview of patients and was validated by a telephone interview with
      a structured questionnaire. In patients from group A, >80% of the coding sequence
      of BRCA2 was analysed; in patients from group B, the regions in which germline
      BRCA2 mutations have been described to be associated with pancreatic cancer were
      screened. RESULTS: Telephone interviews led to reclassification of 7/54 cases
      (13%). Familial aggregation of cancer was found in 24/165 cases (14.5%); six
      patients had a first degree relative with pancreatic cancer (3.6%) and nine
      patients had relatives with breast cancer. Germline BRCA2 mutations were not
      identified in any patient from group A (0/23). Among group B cases, one germline
      variant (T5868G>Asn1880Lys) was found in a 59 year old male without a family
      history of cancer. The 6174delT mutation was not found in any of the 71 cases
      analysed. CONCLUSIONS: The overall prevalence of BRCA2 mutations among patients
      with pancreatic cancer in Spain is low and the 6174delT mutation appears to be
      very infrequent. Our data do not support screening patients with cancer of the
      pancreas for germline BRCA2 mutations to identify relatives at high risk of
      developing this tumour.

PMID- 11950812
TI  - Characteristics of the peroxisome proliferator activated receptor gamma
      (PPARgamma) ligand induced apoptosis in colon cancer cells.
AB  - BACKGROUND: Involvement of peroxisome proliferator activated receptor gamma
      (PPARgamma) in the growth response of colon cancer cells has been suggested.
      AIMS: To investigate the characteristics of PPARgamma induced apoptosis in colon
      cancer cells. METHODS: The effects of ligands for each of the PPAR subtypes
      (alpha, delta, and gamma) on DNA synthesis and cell viability were examined in HT
      29 colon cancer cells. Modulation of apoptosis related gene expression by
      PPARgamma ligands was screened with cDNA arrays, and the results were confirmed
      by quantitative reverse transcription-polymerase chain reaction (RT-PCR)
      analysis. RESULTS: PPARalpha, PPARdelta, and PPARgamma were all expressed in HT
      29 cells. PPARgamma ligands, 15-deoxy-delta(12,)(14)-prostaglandin J2 (15d-PGJ2)
      and troglitazone (TGZ), suppressed DNA synthesis of HT-29 cells whereas ligands
      for PPARalpha and PPARdelta had no significant effects. Both 15d-PGJ2 and TGZ
      induced HT-29 cell death in a dose dependent manner which was associated with an
      increase in fragmented DNA and was sensitive to a caspase inhibitor. Among
      several genes selected by cDNA array screening, quantitative RT-PCR analysis
      confirmed downregulation of c-myc expression and upregulation of c-jun and
      gadd153 expression by 15d-PGJ2 and TGZ. PPARgamma induced apoptosis was
      antagonised by the presence of serum in the culture medium, and interaction
      between PPARgamma signalling and cell survival signalling through the
      phosphatidylinositol 3-kinase pathway was suggested. CONCLUSIONS: As c-myc is an
      important target gene of the adenomatous polyposis coli (APC)/beta-catenin and/or
      APC/gamma-catenin pathway, activation of PPARgamma signalling appears to
      compensate for deregulated c-myc expression caused by mutated APC. The present
      results suggest the potential usefulness of PPARgamma ligands for chemoprevention
      and treatment of colon cancers.

PMID- 11950813
TI  - Outcome of endoscopic sphincterotomy in post cholecystectomy patients with
      sphincter of Oddi dysfunction as predicted by manometry and quantitative
      choledochoscintigraphy.
AB  - BACKGROUND: Sphincter of Oddi dysfunction is diagnosed at manometry and, after
      cholecystectomy, non-invasively at quantitative choledochoscintigraphy. Patients
      may benefit from endoscopic sphincterotomy. AIMS: The aim of this study was to
      assess the usefulness of choledochoscintigraphy compared with manometry in
      predicting outcome of sphincterotomy in post cholecystectomy patients with
      sphincter of Oddi dysfunction. PATIENTS AND METHODS: Thirty patients with biliary
      type pain complying with the Rome diagnostic criteria of sphincter of Oddi
      dysfunction and belonging to biliary group I and II were subjected to clinical
      evaluation, choledochoscintigraphic assessment of the hepatic hilum-duodenum
      transit time, endoscopic retrograde cholangiopancreatography, and perendoscopic
      manometry. Twenty two biliary group I and II patients with prolonged hepatic
      hilum-duodenum transit times were invited to undergo sphincterotomy. Fourteen
      patients underwent sphincterotomy; eight refused. Clinical and scintigraphic
      assessments were performed at follow up. RESULTS: Hepatic hilum-duodenum transit
      time was delayed in all patients with manometric evidence of sphincter of Oddi
      dysfunction, in all biliary group I patients and in 64% of biliary group II
      patients. At follow up, all patients who underwent sphincterotomy were symptom
      free and hepatic hilum-duodenum transit time had either normalised or
      significantly improved. A favourable post sphincterotomy outcome was predicted in
      93% of cases at choledochoscintigraphy and in 57% at manometry. CONCLUSIONS:
      Quantitative choledochoscintigraphy is a useful and non-invasive test to diagnose
      sphincter of Oddi dysfunction as well as a reliable predictor of sphincterotomy
      outcome in post cholecystectomy biliary group I and II patients, irrespective of
      clinical classification and manometric findings.

PMID- 11950814
TI  - Intraduodenal conjugated bile salts exert negative feedback control on gall
      bladder emptying in the fasting state without affecting cholecystokinin release
      or antroduodenal motility.
AB  - BACKGROUND: Intraduodenal bile salts exert negative feedback control on
      postprandial gall bladder emptying. AIMS: We wished to examine whether a similar
      control mechanism occurs in the fasting state. METHODS: Intraduodenal bile salt
      depletion was achieved by 12 g of cholestyramine. Thereafter, in study A (seven
      subjects), the effects on gall bladder volume (by ultrasound) and antroduodenal
      motility of intraduodenal infusions of taurocholate egg yolk-phosphatidylcholine
      micelles were assessed. In study B (nine subjects), the effects on gall bladder
      volume of infusing mixed micelles composed of taurocholate (100 mM) and low (26
      mM) or high (68 mM) amounts of egg yolk-phosphatidylcholine, or low amounts of
      dipalmitoylphosphatidylcholine were determined. RESULTS: Cholestyramine induced
      strong and prolonged gall bladder contraction without cholecystokinin release. In
      study A, micellar infusions increased gall bladder volume without affecting
      migrating motor complex cycle length. In study B, intraduodenal infusion induced
      strong increases in gall bladder volume in the case of taurocholate micelles
      containing low amounts of egg yolk-phosphatidylcholine, moderate increases in
      micelles containing low amounts of dipalmitoylphosphatidylcholine but no change
      in micelles containing high amounts of egg yolk-phosphatidylcholine, in all cases
      without altered plasma cholecystokinin levels. Phosphatidylcholine hydrolysis was
      significantly higher after infusion of egg yolk-phosphatidylcholine compared with
      infusion of dipalmitoylphosphatidylcholine containing micelles. Intermixed
      micellar-vesicular bile salt concentrations (responsible for detergent effects)
      were higher in egg yolk-phosphatidylcholine than in
      dipalmitoylphosphatidylcholine containing model biles and if lyso
      phosphatidylcholine was included. CONCLUSIONS: Intraduodenal bile salts exert
      negative feedback on fasting gall bladder volume. The modulating effects of
      various phospholipids may relate to their effects on intermixed micellar
      vesicular bile salt concentrations.

PMID- 11950815
TI  - The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of
      idiopathic chronic pancreatitis but does not cause the disease.
AB  - BACKGROUND: Mutations in the PRSS1 gene explain most occurrences of hereditary
      pancreatitis (HP) but many HP families have no PRSS1 mutation. Recently, an
      association between the mutation N34S in the pancreatic secretory trypsin
      inhibitor (SPINK1 or PSTI) gene and idiopathic chronic pancreatitis (ICP) was
      reported. It is unclear whether the N34S mutation is a cause of pancreatitis per
      se, whether it modifies the disease, or whether it is a marker of the disease.
      PATIENTS AND METHODS: A total of 327 individuals from 217 families affected by
      pancreatitis were tested: 152 from families with HP, 108 from families with ICP,
      and 67 with alcohol related CP (ACP). Seven patients with ICP had a family
      history of pancreatitis but no evidence of autosomal dominant disease (f-ICP)
      compared with 87 patients with true ICP (t-ICP). Two hundred controls were also
      tested for the N34S mutation. The findings were related to clinical outcome.
      RESULTS: The N34S mutation was carried by five controls (2.5%; allele frequency
      1.25%), 11/87 (13%) t-ICP patients (p=0.0013 v controls), and 6/7 (86%) affected
      (p<0.0001 v controls) and 1/9 (11%) unaffected f-ICP cases. N34S was found in
      4/108 affected HP patients (p=0.724 v controls), in 3/27 (11%) with wild-type and
      in 1/81 (1%) with mutant PRSS1, and 4/67 ACP patients (all p>0.05 v controls).
      The presence of the N34S mutation was not associated with early disease onset or
      disease severity. CONCLUSIONS: The prevalence of the N34S mutation was increased
      in patients with ICP and was greatest in f-ICP cases. Segregation of the N34S
      mutation in families with pancreatitis is unexplained and points to a complex
      association between N34S and another putative pancreatitis related gene.

PMID- 11950816
TI  - Neural alterations in surgical stage chronic pancreatitis are independent of the
      underlying aetiology.
AB  - BACKGROUND AND AIMS: Among various causes, nerve alterations and neuroimmune
      interactions have been suggested to participate in the generation of pain in
      chronic pancreatitis (CP). In this study, we compared neural changes and the
      pattern of perineural inflammatory cell infiltrates in three different
      aetiological forms of CP (alcoholic, idiopathic, and tropical) and evaluated
      whether differences exist between these groups. PATIENTS AND METHODS: A total of
      35 patients with CP (12 tropical, 12 idiopathic, and 11 alcoholic) were included.
      Ten normal pancreatic tissues obtained from healthy organ donors served as
      controls. In all samples, the number of nerves, area of neural tissue, nerve
      size, and percentage of neural tissue and perineural inflammatory cell
      infiltrates were analysed histologically. RESULTS: The median number of nerves
      per 10 mm2 tissue area was 2.3, 4.3, 4.4, and 2.6 in the normal pancreas,
      alcoholic CP, idiopathic CP, and tropical CP, respectively. Median area of neural
      tissue per 10 mm2 was 2550, 21 803, 18 595, and 24 666 microm2 in the normal
      pancreas, alcoholic CP, idiopathic CP, and tropical CP, respectively. Median
      nerve diameter was 36.85 microm in the normal pancreas, 80.6 microm in alcoholic
      CP, 68.95 microm in idiopathic CP, and 93.05 microm in tropical CP. In comparison
      with normal controls, all of these parameters were significantly increased except
      the number of nerves in tropical CP. For all parameters there were no significant
      differences between alcoholic, idiopathic, and tropical CP. When the degree of
      perineural inflammation was evaluated, no differences were observed among the
      three CP groups. CONCLUSIONS: Independent of the underlying aetiology, CP is
      associated with an increase in neural tissue, and neural alterations occur in a
      similar fashion irrespective of the type of initiating event.

PMID- 11950817
TI  - Mutations in serine protease inhibitor Kazal type 1 are strongly associated with
      chronic pancreatitis.
AB  - BACKGROUND: Although chronic pancreatitis is associated with risk factors such as
      alcoholism, hyperparathyroidism, and hypertriglyceridaemia, little is known of
      the actual aetiology of the disease. It is thought that inappropriate activation
      of trypsinogen causes pancreatitis, and indeed in cases of hereditary
      pancreatitis mutations of cationic trypsinogen (PRSS1) have been described. As
      serine protease inhibitor Kazal type 1 (SPINK1) is a potent natural inhibitor of
      pancreatic trypsin activity, we hypothesised that SPINK1 mutations would be more
      common than expected among an unselected cohort of adult chronic pancreatitis
      patients. AIMS: To detect the prevalence of SPINK1 mutations in a cohort of
      chronic pancreatitis patients. METHODS: DNA was isolated from a cohort of 115
      adult patients with chronic pancreatitis of alcoholic (n=72), hereditary (n=10),
      idiopathic (n=24), and miscellaneous (n=9) origin. We performed mutational
      analysis for two PRSS1 mutations (R122H, N29I) and four specific SPINK1 gene
      mutations (M1T, L14P, N34S, P55S) and compared the results with a control group
      of 120 healthy Dutch subjects. RESULTS: In six of the 10 patients that fulfilled
      the criteria for hereditary pancreatitis, but in none of the control subjects,
      mutations in the PRSS1 gene were found. In 14 patients we detected a SPINK1
      mutation. Eleven patients were heterozygous for the N34S mutation and sequencing
      confirmed the homozygous state of N34S in a brother and sister. Two patients
      carried the P55S mutation, one as a compound heterozygote with N34S. The M1T and
      L14P SPINK1 mutations were not found in our cohort. The N34S mutation was
      detected in only two of 120 controls, while the P55S, M1T, and L14P mutations
      were absent in the same group. Patients with the N34S allele had a later onset of
      disease than those with PRSS1 gene mutations but earlier onset compared with the
      mutation negative group. CONCLUSION: Identification of SPINK1 mutations in 12.2%
      of patients with adult alcoholic and idiopathic chronic pancreatitis suggests an
      important role for SPINK1 as a predisposing factor in adult chronic pancreatitis.

PMID- 11950819
TI  - Histology predicts cirrhotic evolution of post transplant hepatitis C.
AB  - BACKGROUND: Hepatitis C recurring after orthotopic liver transplantation varies
      in severity and some patients rapidly develop fully established liver cirrhosis.
      Neither clinical nor biological markers of such rapid cirrhotic evolution are
      available. AIM: To assess the value of histology in identifying patients who will
      develop cirrhosis shortly after liver transplantation. PATIENTS AND METHODS: Only
      cases of recurrent hepatitis C diagnosed by both hepatitis C virus-RNA positive
      serum and liver changes consistent with hepatitis, with no other causes of
      allograft injury, were considered. A total of 128 liver biopsies were scored from
      29 consecutive patients with a mean follow up of 48 (13.97) months. The
      histological activity index was evaluated according to Ishak et al. The time of
      the first histological diagnosis of recurrent hepatitis C in the absence of
      rejection was defined as time of histological recurrence (RHC-T). RESULTS: First
      histological diagnosis of recurrent hepatitis with no features of rejection was
      obtained at the six month biopsy in 23 of 29 cases. By the end of follow up, nine
      patients had developed cirrhosis (mean follow up 38 (14.39) months (range 18
      60)). The remainder (mean follow up 46 (13.40) months (24-72)) showed a spectrum
      of fibrosis but no cirrhosis. Severe necroinflammatory lesions at RHC-T
      significantly correlated with rapid development of cirrhosis. At the RHC-T
      biopsy, only cases evolving into cirrhosis showed confluent necrosis. The median
      value of the histological activity index was 11 (mean 11.11 (1.76) (range 9-14))
      in patients who developed cirrhosis and four (mean 4 (1.78) (range 1-8)) in the
      others (p<0.0001). A histological activity index > or =9 was associated with
      rapid development of cirrhosis in 100% of cases. CONCLUSIONS: After liver
      transplantation, the histological activity of recurrent hepatitis C predicts the
      risk of development of cirrhosis. By adopting Ishak's scoring system, a
      histological activity index > or =9 was 100% sensitive/specific in identifying
      subjects who rapidly developed cirrhosis.

PMID- 11950818
TI  - Infection rate and spontaneous seroreversion of anti-hepatitis C virus during the
      natural course of hepatitis C virus infection in the general population.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is common worldwide but there are
      different prevalence rates in different countries. Data on the incidence of HCV
      in the general population are scarce. Spontaneous viral clearance occurs in 10
      25% of infected individuals after acute infection yet controversy exists
      regarding the frequency of spontaneous clearance during the natural course of HCV
      infection in the general population. AIMS: Anti-HCV prevalence, HCV infection
      rate, and the kinetics of anti-HCV were studied in a cross section of the general
      population of central Italy. STUDY POPULATION AND METHODS: Anti-HCV prevalence
      (EIA-3 Ortho, RIBA-3 Ortho Chiron) was estimated in 3884 randomly selected
      individuals. Infection rate and antibody kinetics were estimated in 2032
      participants for whom a second blood sample was taken after a median follow up of
      seven years. HCV-RNA determination by polymerase chain reaction was performed on
      follow up sera. RESULTS: The overall confirmed anti-HCV prevalence was 2.4%. Two
      participants seroconverted for anti-HCV, giving an overall infection rate of 1.4
      cases per 10 000 person years (95% confidence interval 0.2-5.2 per 10 000 person
      years). Of the 36 individuals confirmed as anti-HCV positive at enrollment, seven
      (19.4%) showed complete seroreversion. Seven (87%) of the eight individuals with
      indeterminate results at enrollment were serologically non-reactive at the end of
      follow up. Of the 25 participants confirmed to be anti-HCV positive at both
      enrollment and follow up, 23 (92.0%) with stable serological profiles tested
      positive for HCV-RNA at the end of follow up. CONCLUSIONS: There is still a
      permanent risk, although low, of HCV spread in the general population in an area
      of low level endemicity. In this setting, a wide spectrum of modifications of
      viral and antibody patterns can be observed in HCV infected patients.

PMID- 11950820
TI  - Effect of ursodeoxycholic acid on methionine adenosyltransferase activity and
      hepatic glutathione metabolism in rats.
AB  - BACKGROUND AND AIMS: Both bile salts and glutathione participate in the
      generation of canalicular bile flow. In this work, we have investigated the
      effect of different bile salts on hepatic glutathione metabolism. METHODS: Using
      the isolated and perfused rat liver, we studied hepatic glutathione content, and
      metabolism and catabolism of this compound in livers perfused with taurocholate,
      ursodeoxycholate, or deoxycholate. RESULTS: We found that in livers perfused with
      ursodeoxycholate, levels of glutathione and the activity of methionine
      adenosyltransferase (an enzyme involved in glutathione biosynthesis) were
      significantly higher than in livers perfused with other bile salts. In
      ursodeoxycholate perfused livers, methionine adenosyltransferase showed a
      predominant tetrameric conformation which is the isoform with highest activity at
      physiological concentrations of substrate. In contrast, the dimeric form
      prevailed in livers perfused with taurocholate or deoxycholate. The hepatic
      activities of gamma-glutamylcysteine synthetase and gamma-glutamyltranspeptidase,
      enzymes involved, respectively, in biosynthetic and catabolic pathways of
      glutathione, were not modified by bile salts. CONCLUSIONS: Ursodeoxycholate
      specifically enhanced methionine adenosyltransferase activity and hepatic
      glutathione levels. As glutathione is a defensive substance against oxidative
      cell damage, our observations provide an additional explanation for the known
      hepatoprotective effects of ursodeoxycholate.

PMID- 11950821
TI  - Impaired tuftsin activity in cirrhosis: relationship with splenic function and
      clinical outcome.
AB  - BACKGROUND: Cirrhotic patients show increased susceptibility to bacterial
      infections. It is not known whether tuftsin deficiency, which is associated with
      an increased incidence of infections in many disease states, is present in
      cirrhosis. Our aims were to determine whether tuftsin activity is deficient in
      cirrhosis and if so, whether this deficiency is related to splenic function,
      contributes to altered neutrophil granulocyte function, or influences the
      occurrence of bacterial infections and patient survival. METHODS: Tuftsin
      activity and splenic function were assessed in 31 patients with liver cirrhosis
      and 31 healthy subjects. The phagocytic activity of neutrophil granulocytes from
      23 patients was tested in vitro with addition of both autologous and pooled sera
      from healthy subjects. In 10 patients and eight controls it was also tested with
      addition of synthetic tuftsin. Patients were followed up until death or liver
      transplantation. RESULTS: Patients had reduced tuftsin activity (median 8% (range
      3-24.5)) compared with controls (17% (11.5-37)) (p<0.001) and a higher pitted red
      cell count (p<0.001). Tuftsin activity was correlated with pitted cell count
      (p=0.02) and the Child-Pugh score (p=0.002). Nineteen of 23 patients showed
      deficient phagocytic activity of neutrophil granulocytes, which was correlated
      with tuftsin activity (p<0.001), improved in all cases but one with addition of
      serum from healthy subjects, and normalised with addition of synthetic tuftsin.
      Reduced tuftsin activity did not influence patient survival but was associated
      with a higher incidence of bacterial infections (p=0.029). COMMENT: Tuftsin
      activity was reduced in cirrhosis, and contributed to impaired phagocytic
      activity of neutrophil granulocytes. Such an abnormality appears to be related to
      impaired splenic function and severity of cirrhosis, and probably favours the
      occurrence of bacterial infections.

PMID- 11950822
TI  - Characteristics of autoimmune hepatitis in patients who are not of European
      Caucasoid ethnic origin.
AB  - BACKGROUND: Significant diversity in disease severity has been identified for
      autoimmune disorders among different ethnic groups but there is a lack of data on
      autoimmune hepatitis (AIH) in populations other than those of European Caucasoid
      (EC) or Japanese extraction. AIMS: To assess the clinical features, response to
      therapy, and eventual outcome in AIH patients of non-EC ethnicity. METHODS: A
      retrospective review of a regularly updated database of patients with AIH
      referred to liver outpatient clinics at King's College Hospital, London, since
      1983. RESULTS: Twelve patients were identified (10 female; six African, five
      Asian, one Arabic; median age at presentation 30 years (range 12-58)) who
      satisfied international criteria for type 1 (11 cases) or type 2 (one case) AIH.
      Nine (75%) had cholestatic serum biochemistry and three (25%) had mild biliary
      changes on liver biopsy without definitive features of primary biliary cirrhosis
      or cholangiographic evidence of primary sclerosing cholangitis. Four showed a
      complete biochemical response to standard prednisolone with or without
      azathioprine therapy, three partial, and five no response. Four have required
      liver transplantation for intractable disease. By comparison with 180 EC patients
      with definite AIH attending during the same period, the non-EC patients were
      younger (p<0.05), presented with cholestatic biochemistry (p=0.014), and
      morphological biliary features more frequently (p<0.0005) and showed a poorer
      initial response to standard therapy (p<0.0005). CONCLUSIONS: Clinical expression
      of AIH in non-EC patients seems to differ in important respects from that in EC
      or Japanese patients. Management of such patients is challenging and may require
      alternative or more aggressive treatment strategies.

PMID- 11950823
TI  - Percutaneous evacuation (PEVAC) of multivesicular echinococcal cysts with or
      without cystobiliary fistulas which contain non-drainable material: first results
      of a modified PAIR method.
AB  - BACKGROUND: Surgery is the treatment of choice in echinococcal cysts with
      cystobiliary fistulas. PAIR (puncture, aspiration, injection, and reaspiration of
      scolecidals) is contraindicated in these cases. AIM: To evaluate a modified PAIR
      method for percutaneous treatment of multivesicular echinococcal cysts with or
      without cystobiliary fistulas which contain non-drainable material. PATIENTS:
      Twelve patients were treated: 10 patients with multivesicular cysts which
      contained non-drainable material and were complicated by spontaneous intrabiliary
      rupture, secondary cystobiliary fistulas, cyst infection, or obstructed portal or
      hepatic veins; and two patients with large univesicular cysts and a ruptured
      laminated membrane, one obstructing the portal and hepatic veins and one a
      suspected cystobiliary fistula. METHODS: The methods used, termed PEVAC
      (percutaneous evacuation of cyst content), involved the following steps:
      ultrasound guided cyst puncture and aspiration of cyst fluid to release
      intracystic pressure and thereby to avoid leakage; insertion of a large bore
      catheter; aspiration and evacuation of daughter cysts and endocyst by injection
      and reaspiration of isotonic saline; cystography; injection of scolecidals only
      if no cystobiliary fistula was present; external drainage of cystobiliary
      fistulas combined with endoprosthesis or sphincterotomy; catheter removal after
      complete cyst collapse and closure of the cystobiliary fistula. RESULTS: In all
      12 patients initial cyst size was 13.1 (6-20) cm (mean (range)). At follow up
      17.9 (4-30) months after PEVAC, seven cysts had disappeared and five cysts had
      decreased to 2.4 (1-4) cm (p=0.002). In eight patients with multivesicular cysts,
      a cystobiliary fistula, and infection, cyst size was 12.5 (6-20) cm, catheter
      time 72.3 (28-128) days, and hospital stay 38.1 (20-55) days. At 17.3 (4-28)
      months of follow up, six cysts had disappeared and in two cysts residual size was
      1 and 2.9 cm, respectively (p=0.012). In four patients without a cystobiliary
      fistula, cyst size was 14.4 (12.7-16) cm, catheter time 8.8 (3-13) days, and
      hospital stay 11.5 (8-14) days. At 19.3 (9-30) months of follow up, one cyst had
      disappeared and three cysts were 85 (69-94)% smaller (2.2 (1-4) cm) (p=0.068).
      CONCLUSION: PEVAC is a safe and effective method for percutaneous treatment of
      multivesicular echinococcal cysts with or without cystobiliary fistulas which
      contain non-drainable material.

PMID- 11950824
TI  - A survey on gastroenterology training in Europe.
AB  - BACKGROUND: Specialist training in gastroenterology and hepatology is not
      standardised in different European countries. AIM: The aim of this survey was to
      assess the different teaching and socioeconomic aspects of training programmes in
      Europe. METHODS: Seventy questionnaires were distributed to last year trainees or
      newly graduated gastroenterologists. Forty two respondents (60%) from 34 major
      training centres in 10 different European countries replied. RESULTS: Overall,
      the data revealed major diversity for all aspects analysed, between and within
      the different European countries. Both the duration of training (range 4-10.4
      years) and workload (range 48.5-89.2 hours per week) differed markedly between
      countries. The average number of endoscopic procedures (gastroscopies, range 300
      2600; colonoscopies, range 73-550; endoscopic retrograde
      cholangiopancreatographies, range 1-385) differed also. One third of last year
      trainees reported that they felt uncertain in some endoscopic procedure. The
      European trainee was on call for 5-6 nights a month on average (range 1-8).
      Monthly wages differed considerably between countries, ranging from 767 to 2180
      Euro. CONCLUSION: We found major differences in the professional aspects and
      socioeconomic conditions of gastroenterologist/hepatologist training in 10
      different European countries, probably leading to differences in quality of
      training. In several countries or centres the average number of procedures was
      below the threshold issued by the European Board of Gastroenterology or the
      American Gastroenterological Association. Issuing a European diploma for
      gastroenterology is a valuable effort towards meeting this problem. Further
      studies are needed to re-evaluate the training programmes in Europe and to define
      threshold numbers and technical end points for assessment of endoscopic skills.

PMID- 11950825
TI  - Role of alpha-1-antichymotrypsin deficiency in promoting cirrhosis in two
      siblings with heterozygous alpha-1-antitrypsin deficiency phenotype SZ.
AB  - BACKGROUND: Alpha-1-antitrypsin (A1AT) deficiency is the most common inherited
      metabolic disorder with the potential to cause injury in the lung and liver.
      Recent reports suggested that alpha-1-antichymotrypsin (A1AC) deficiency may also
      be a possible cause of chronic liver disease. However, it has received little
      attention and is rarely investigated in the clinical setting. AIMS: To assess the
      role of A1AC deficiency in the pathogenesis of chronic liver disease in two
      siblings with heterozygous A1AT phenotype Pi SZ. PATIENTS: Two adult siblings
      with an A1AT Pi SZ phenotype and reduced levels of A1AC consistent with
      heterozygosity who developed cirrhosis and underwent liver transplantation.
      METHODS AND RESULTS: A1AT and A1AC levels in plasma measured by
      electroimmunoassay were 74 mg/dl and 90 mg/dl (140-470) and 0.12 mg/ml and 0.14
      mg/ml (0.173-0.46), respectively. Immunohistochemistry revealed an apparent
      accumulation of both A1AT and A1AC in hepatocytes. A previously reported point
      mutation in exon III (Pro(229) to Ala substitution) of the A1AC gene was not
      detected by polymerase chain reaction amplification and a single strand
      conformation polymorphism analysis. CONCLUSIONS: Our report represents the first
      case of two siblings with A1CA phenotype Pi SZ who developed cirrhosis and
      underwent liver transplantation. Both siblings were heterozygous for A1AT and
      A1AC deficiency suggesting that combined deficiency of these two major serine
      protease inhibitors may enhance the risk of developing liver disease.

PMID- 11950826
TI  - Ablative therapy for liver tumours.
AB  - Established ablative therapies for the treatment of primary and secondary liver
      tumours, including percutaneous ethanol injection, cryotherapy, and
      radiofrequency ablation, are discussed. Newer techniques such as magnetic
      resonance imaging guided laser interstitial thermal therapy of liver tumours has
      produced a median survival rate of 40.8 months after treatment. The merits of
      this newly emerging technique are discussed, together with future developments,
      such as focused ultrasound therapy, which holds the promise of non-invasive
      thermoablation treatment on an outpatient basis.

PMID- 11950828
TI  - A Paneth cell surrogate?

PMID- 11950827
TI  - Intestinal intraepithelial lymphocytes and anti-transglutaminase in a screening
      algorithm for coeliac disease.

PMID- 11950829
TI  - The changing scope of colorectal cancer.

PMID- 11950831
TI  - Involvement of the second extracellular loop (E2) of the neurokinin-1 receptor in
      the binding of substance P. Photoaffinity labeling and modeling studies.
AB  - Substance P (SP) interacts with the neurokinin-1 (NK-1) G-protein-coupled
      receptor, which has been cloned in several species. In the present study, the
      domains of the NK-1 receptor involved in the binding of SP and SP-(7-11) C
      terminal fragment have been analyzed using two peptide analogs containing the
      photoreactive amino acid para-benzoylphenylalanine ((p-Bz)Phe) in position 8 of
      their sequence. This study was carried out with [BAPA-Lys(6),(p
      Bz)Phe(8),Pro(9),Met(O(2))(11)]SP-(7-11) and [BAPA(0),(p-Bz)Phe(8)]SP on both rat
      and human NK-1 receptors expressed in CHO cells. Combined trypsin and endo-GluC
      enzymatic complete digestions and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry analysis led to the identification of the same
      domain of covalent interaction, (173)TMPSR(177), for the two photoactivatable
      peptides. Further digestion of this fragment with carboxypeptidase Y led to the
      identification of (173)TMP(175) in the second extracellular loop (E2) of the NK-1
      receptor as the site of covalent attachment. Models of the conformation of this
      E2 loop in the human NK-1 receptor were generated using two different strategies,
      one based on homology with bovine rhodopsin and the other based on the solution
      conformation preferences of a synthetic peptide corresponding to the E2 loop.

PMID- 11950832
TI  - Regulation of T cell receptor CD3zeta chain expression by L-arginine.
AB  - L-Arg plays a central role in the normal function of several organ systems
      including the immune system. L-Arg can be depleted by arginase I produced by
      macrophages and hepatocytes in several disease states such as trauma and sepsis
      and following liver transplantation. The decrease in L-Arg levels induces a
      profound decrease in T cell function through mechanisms that have remained
      unclear. The data presented here demonstrate that Jurkat T cells cultured in
      medium without L-Arg (L-Arg-free RPMI) have a rapid decrease in the expression of
      the T cell antigen receptor zeta chain (CD3zeta), the principal signal
      transduction element in this receptor, and a decrease in T cell proliferation.
      This phenomenon is completely reversed by the replenishment of L-Arg but not
      other amino acids. These changes are not caused by cell apoptosis; instead, the
      diminished expression of CD3zeta protein is paralleled by a decrease in CD3zeta
      mRNA. This change in CD3zeta mRNA expression is not caused by a decrease in the
      transcription rate but rather by a significantly shorter CD3zeta mRNA half-life.
      This mechanism is sensitive to cycloheximide. Therefore, the regulation of L-Arg
      concentration in the microenvironment could represent an important mechanism to
      modulate the expression of CD3zeta and the T cell receptor and consequently of T
      cell function.

PMID- 11950833
TI  - Delta/notch-like epidermal growth factor (EGF)-related receptor, a novel EGF-like
      repeat-containing protein targeted to dendrites of developing and adult central
      nervous system neurons.
AB  - We have identified a novel epidermal growth factor (EGF)-like repeat-containing
      single-pass transmembrane protein that is specifically expressed in the
      developing and mature central nervous system. Sequence analysis revealed that the
      10 EGF-like repeats in the extracellular domain are closely related to those of
      the developmentally important receptor Notch and its ligand Delta. We thus named
      the molecule Delta/Notch-like EGF-related receptor (DNER). DNER protein is
      strongly expressed in several types of post-mitotic neurons, including cortical
      and hippocampal pyramidal neurons, cerebellar granule cells, and Purkinje cells.
      DNER protein is localized to the dendritic plasma membrane and endosomes and is
      excluded from the axons, even when overexpressed. The tyrosine-based sorting
      motif in the cytoplasmic domain is required for dendritic targeting of DNER.
      Direct in vivo binding of DNER to the coat-associated protein complex AP-1
      strongly suggests that DNER undergoes AP-1-dependent sorting to the
      somatodendritic compartments from the trans-Golgi network and subsequent passage
      through the endosomal system.

PMID- 11950834
TI  - SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the
      activation of p53-mediated transcription.
AB  - The SWI/SNF complex is required for the transcription of several genes and has
      been shown to alter nucleosome structure in an ATP-dependent manner. The tumor
      suppressor protein p53 displays growth and transformation suppression functions
      that are frequently lost in mutant p53 proteins detected in various cancers.
      Using genetic and biochemical approaches, we show that several subunits of the
      human SWI/SNF complex bind to the tumor suppressor protein p53 in vivo and in
      vitro. The transactivation function of p53 is stimulated by overexpression of
      hSNF5 and BRG-1 and dominant forms of hSNF5 and BRG-1 repress p53-dependent
      transcription. Chromatin immunoprecipitation assay shows that hSNF5 and BRG-1 are
      recruited to a p53-dependent promoter in vivo. Overexpression of dominant
      negative forms of either hSNF5 or BRG-1 inhibited p53-mediated cell growth
      suppression and apoptosis. Molecular connection between p53 and the SWI/SNF
      complex implicates that (i) the SWI/SNF complex is necessary for p53-driven
      transcriptional activation, and (ii) the SWI/SNF complex plays an important role
      in p53-mediated cell cycle control.

PMID- 11950835
TI  - Anabaena sp. PCC 7119 flavodoxin as electron carrier from photosystem I to
      ferredoxin-NADP+ reductase. Role of Trp(57) and Tyr(94).
AB  - The influence of the amino acid residues sandwiching the flavin ring in
      flavodoxin (Fld) from the cyanobacterium Anabaena sp. PCC 7119 in complex
      formation and electron transfer (ET) with its natural partners, photosystem I
      (PSI) and ferredoxin-NADP(+) reductase (FNR), was examined in mutants of the key
      residues Trp(57) and Tyr(94). The mutants' ability to form complexes with either
      FNR or PSI is similar to that of wild-type Fld. However, some of the mutants
      exhibit altered kinetic properties in their ET processes that can be explained in
      terms of altered flavin accessibility and/or thermodynamic parameters. The most
      noticeable alteration is produced upon replacement of Tyr(94) by alanine. In this
      mutant, the processes that involve the transfer of one electron from either PSI
      or FNR are clearly accelerated, which might be attributable to a larger
      accessibility of the flavin to the reductant. However, when the opposite ET flow
      is analyzed with FNR, the reduced Y94A mutant transfers electrons to FNR slightly
      more slowly than wild type. This can be explained thermodynamically from a
      decrease in driving force due to the significant shift of 137 mV in the reduction
      potential value for the semiquinone/hydroquinone couple (E(1)) of Y94A, relative
      to wild type (Lostao, A., Gomez-Moreno, C., Mayhew, S. G., and Sancho, J. (1997)
      Biochemistry 36, 14334-14344). The behavior of the rest of the mutants can be
      explained in the same way. Overall, our data indicate that Trp(57) and Tyr(94) do
      not play any active role in flavodoxin redox reactions providing a path for the
      electrons but are rather involved in setting an appropriate structural and
      electronic environment that modulates in vivo ET from PSI to FNR while providing
      a tight FMN binding.

PMID- 11950836
TI  - Crystal structure of beta 1,3-glucuronyltransferase I in complex with active
      donor substrate UDP-GlcUA.
AB  - Beta1,3-glucuronyltransferase (GlcAT-I) is an essential enzyme involved in
      heparan sulfate and chondroitin sulfate biosynthesis. GlcAT-I is an inverting
      glycosyltransferase that catalyzes the transfer of glucuronic acid (GlcUA) to the
      common growing linker region Galbeta1-3Galbeta1-4Xyl that is attached to a serine
      side chain of a core protein. Previously the structure of GlcAT-I has been solved
      in the presence of the donor product UDP and an acceptor analog Galbeta1
      3Galbeta1-4Xyl (Pedersen, L. C., Tsuchida, K., Kitagawa, H., Sugahara, K.,
      Darden, T. A. & Negishi, M. (2000) J. Biol. Chem. 275, 34580-34585). Here we
      report the x-ray crystal structure of GlcAT-I in complex with the complete donor
      UDP-GlcUA, thereby providing structures of an inverting glycosyltransferase in
      which both the complete donor and acceptor substrates are present in the active
      site. This structure supports the in-line displacement reaction mechanism
      previously proposed. It also provides information on the essential amino acid
      residues that determine donor substrate specificity.

PMID- 11950837
TI  - Single amino acid substitution (G456A) in the vicinity of the GTP binding domain
      of human housekeeping glutamate dehydrogenase markedly attenuates GTP inhibition
      and abolishes the cooperative behavior of the enzyme.
AB  - Human glutamate dehydrogenase (GDH) exists in two isoforms encoded by the GLUD1
      and GLUD2 genes, respectively. Although the two enzymes share in their mature
      form all but 15 of their 505 amino acids, they differ markedly in their
      allosteric regulation. To identify the structural basis for these allosteric
      characteristics, we performed site-directed mutagenesis on the human GLUD1 gene
      at sites that differ from the GLUD2 gene using a cloned GLUD1 cDNA. Results
      showed that substitution of Ala for Gly-456, but not substitution of His for Arg
      470 or Ser for Asn-498, renders the enzyme markedly resistant to GTP inhibition
      (IC(50) = 2.80 microm) as compared with the wild type GLUD1-derived GDH (IC(50) =
      0.19 microm). The G456A mutation abolished the cooperative behavior of the
      enzyme, as revealed by the GTP inhibitory curves. The catalytic and kinetic
      properties of the G456A mutant and its activation by ADP were comparable with
      those of the wild type GDH. Gly-456 lies in a very tightly packed region of the
      GDH molecule, and its replacement by Ala may lead to steric clashes with
      neighboring amino acids. These, in turn, may affect the conformational state of
      the protein that is essential for the allosteric regulation of the enzyme by GTP.

PMID- 11950838
TI  - Ceramide biosynthesis is required for the formation of the oligomeric H+-ATPase
      Pma1p in the yeast endoplasmic reticulum.
AB  - The yeast plasma membrane H(+)-ATPase Pma1p is one of the most abundant proteins
      to traverse the secretory pathway. Newly synthesized Pma1p exits the endoplasmic
      reticulum (ER) via COPII-coated vesicles bound for the Golgi. Unlike most
      secreted proteins, efficient incorporation of Pma1p into COPII vesicles requires
      the Sec24p homolog Lst1p, suggesting a unique role for Lst1p in ER export.
      Vesicles formed with mixed Sec24p-Lst1p coats are larger than those with Sec24p
      alone. Here, we examined the relationship between Pma1p biosynthesis and the
      requirement for this novel coat subunit. We show that Pma1p forms a large
      oligomeric complex of >1 MDa in the ER, which is packaged into COPII vesicles.
      Furthermore, oligomerization of Pma1p is linked to membrane lipid composition;
      Pma1p is rendered monomeric in cells depleted of ceramide, suggesting that
      association with lipid rafts may influence oligomerization. Surprisingly,
      monomeric Pma1p present in ceramide-deficient membranes can be exported from the
      ER in COPII vesicles in a reaction that is stimulated by Lst1p. We suggest that
      Lst1p directly conveys Pma1p into a COPII vesicle and that the larger size of
      mixed Sec24pLst1p COPII vesicles is not essential to the packaging of large
      oligomeric complexes.

PMID- 11950839
TI  - A small molecule ubiquitination inhibitor blocks NF-kappa B-dependent cytokine
      expression in cells and rats.
AB  - A small molecule inhibitor of NF-kappaB-dependent cytokine expression was
      discovered that blocked tumor necrosis factor (TNF) alpha-induced IkappaB(alpha)
      degradation in MM6 cells but not the degradation of beta-catenin in Jurkat cells.
      Ro106-9920 blocked lipopolysaccharide (LPS)-dependent expression of TNFalpha,
      interleukin-1beta, and interleukin-6 in fresh human peripheral blood mononuclear
      cells with IC(50) values below 1 microm. Ro106-9920 also blocked TNFalpha
      production in a dose-dependent manner following oral administration in two acute
      models of inflammation (air pouch and LPS challenge). Ro106-9920 was observed to
      inhibit an ubiquitination activity that does not require betaTRCP but associates
      with IkappaB(alpha) and will ubiquitinate IkappaB(alpha) S32E,S36E
      (IkappaB(alpha)(ee)) specifically at lysine 21 or 22. Ro106-9920 was identified
      in a cell-free system as a time-dependent inhibitor of IkappaB(alpha)(ee)
      ubiquitination with an IC(50) value of 2.3 +/- 0.09 microm. The ubiquitin E3
      ligase activity is inhibited by cysteine-alkylating reagents, supported by
      E2UBCH7, and requires cIAP2 or a cIAP2-associated protein for activity. These
      activities are inconsistent with what has been reported for SCF(betaTRCP), the
      putative E3 for IkappaB(alpha) ubiquitination. Ro106-9920 was observed to be
      selective for IkappaB(alpha)(ee) ubiquitination over the ubiquitin-activating
      enzyme (E1), E2UBCH7, nonspecific ubiquitination of cellular proteins, and 97
      other molecular targets. We propose that Ro106-9920 selectively inhibits an
      uncharacterized but essential ubiquitination activity associated with LPS- and
      TNFalpha-induced IkappaB(alpha) degradation and NF-kappaB activation.

PMID- 11950840
TI  - Detecting protein-phospholipid interactions. Epidermal growth factor-induced
      activation of phospholipase D1b in situ.
AB  - Phospholipase D (PLD) proteins have been identified in secretory and endocytic
      vesicles, consistent with their proposed role in regulating membrane traffic.
      However, their sites of catalytic action remain obscure. We have developed here a
      novel, analytical approach to monitor PLD activation in intact cells employing
      lifetime imaging microscopy to measure fluorescence resonance energy transfer
      between protein and membrane phospholipid. Verification and application of this
      technique demonstrates a dispersed endosomal, epidermal growth factor-induced
      activation of the PLD1b isoform. Application of this approach will facilitate the
      spatial resolution of many protein-phospholipid interactions that are key events
      in the regulation of cellular processes.

PMID- 11950841
TI  - Selective association of protein kinase C with 14-3-3 zeta in neuronally
      differentiated PC12 Cells. Stimulatory and inhibitory effect of 14-3-3 zeta in
      vivo.
AB  - The 14-3-3 protein is a family of highly conserved acidic proteins found in a
      wide range of eukaryotes from yeast to mammals. 14-3-3 acts as an adapter protein
      and interacts with signaling molecules including protein kinase C (PKC). Although
      14-3-3 zeta was originally characterized as an endogenous PKC inhibitor, it was
      reported to activate PKC in vitro, but the in vivo regulation of PKC by 14-3-3 is
      still not well understood. To examine the regulation of PKC by 14-3-3 in the
      cell, we have generated a sub-cell line, PC12-B3, that stably expresses FLAG
      epitope-tagged 14-3-3 zeta isoform in PC12 cells. Here we show that PKC-alpha and
      PKC-epsilon become associated with 14-3-3 zeta when the cells are neuronally
      differentiated by nerve growth factor. We found that the immunoprecipitate by
      anti-FLAG antibody contains constitutive and autonomous Ca(2+)-independent non
      classical PKC activity. In contrast, the FLAG immunoprecipitate has no Ca(2+)
      dependent classical PKC activity despite the fact that PKC-alpha is present in
      the FLAG immunoprecipitate from differentiated PC12-B3 cells. Our results show
      that the association with 14-3-3 zeta has distinct effects on classical PKC and
      non-classical PKC activity.

PMID- 11950842
TI  - Nitric oxide reacts with the single-electron reduced active site of cytochrome c
      oxidase.
AB  - The reduction kinetics of the mutants K354M and D124N of the Paracoccus
      denitrificans cytochrome oxidase (heme aa(3)) by ruthenium hexamine was
      investigated by stopped-flow spectrophotometry in the absence/presence of NO.
      Quick heme a reduction precedes the biphasic heme a(3) reduction, which is
      extremely slow in the K354M mutant (k(1) = 0.09 +/- 0.01 s(-1); k(2) = 0.005 +/-
      0.001 s(-1)) but much faster in the D124N aa(3) (k(1) = 21 +/- 6 s(-1); k(2) =
      2.2 +/- 0.5 s(-1)). NO causes a very large increase (>100-fold) in the rate
      constant of heme a(3) reduction in the K354M mutant but only a approximately 5
      fold increase in the D124N mutant. The K354M enzyme reacts rapidly with O(2) when
      fully reduced but is essentially inactive in turnover; thus, it was proposed that
      impaired reduction of the active site is the cause of activity loss. Since at
      saturating [NO], heme a(3) reduction is approximately 100-fold faster than the
      extremely low turnover rate, we conclude that, contrary to O(2), NO can react not
      only with the two-electron but also with the single-electron reduced active site.
      This mechanism would account for the efficient inhibition of cytochrome oxidase
      activity by NO in the wild-type enzyme, both from P. denitrificans and from beef
      heart. Results also suggest that the H(+)-conducting K pathway, but not the D
      pathway, controls the kinetics of the single-electron reduction of the active
      site.

PMID- 11950843
TI  - Co-requirement of cyclic AMP- and calcium-dependent protein kinases for
      transcriptional activation of cholecystokinin gene by protein hydrolysates.
AB  - Little is known about the mechanisms by which protein-derived nutrients regulate
      hormone gene expression in the intestine. We have previously reported that
      protein hydrolysates (i.e. peptones), which are representative of the protein
      fraction in the lumen, increased cholecystokinin (CCK) gene transcription in the
      STC-1 enteroendocrine cell line. In the present work, we examined the
      intracellular events evoked by peptones to stimulate CCK gene transcription. In
      STC-1 cells, peptones stimulated cyclic AMP production and protein kinase A (PKA)
      activity. This was associated with a nuclear translocation of the PKA catalytic
      subunit and with a PKA-dependent phosphorylation of the CRE-binding protein
      (CREB) at Ser(133). Using transient transfection experiments and reporter
      luciferase assays, we show that peptone-stimulated transcriptional activity of
      the CCK gene promoter was significantly decreased when the PKA pathway was
      inhibited. Furthermore, the intracellular calcium chelator 1,2-bis-(O
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-tetra(acetoxymethyl)ester
      completely inhibited peptone-induced stimulation of the CCK gene promoter
      activity, phosphorylation of CREB, and PKA activity. Peptones increased, in a
      calcium-dependent manner, the phosphorylation of extracellular signal-regulated
      protein kinases 1 and 2 (ERK1/2) and the MEK inhibitor PD98059 decreased the
      peptone-induced stimulation of CCK gene promoter activity. This stimulation was
      also reduced by 30% in the presence of the calcium/calmodulin-dependent protein
      kinase (CaMK) inhibitor KN-93. Total inhibition was obtained when the PKA, ERK,
      and CaMK pathways were simultaneously blocked with appropriate inhibitors to
      these pathways. These results demonstrate the simultaneous involvement of cAMP-
      and calcium-dependent protein kinases in the stimulation of intestinal CCK gene
      transcription by protein-derived nutrients.

PMID- 11950844
TI  - A short segment of the R domain of cystic fibrosis transmembrane conductance
      regulator contains channel stimulatory and inhibitory activities that are
      separable by sequence modification.
AB  - The regulatory (R) domain of the cystic fibrosis transmembrane conductance
      regulator (CFTR) contains consensus phosphorylation sites for cAMP-dependent
      protein kinase (PKA) that are the basis for physiological regulation of the CFTR
      chloride channel. A short peptide segment in the R domain with a net negative
      charge of B9 (amino acids 817-838, NEG2) and predicted helical tendency is shown
      to play a critical role in CFTR chloride channel function. Deletion of NEG2 from
      CFTR completely eliminates the PKA dependence of channel activity. Exogenous NEG2
      peptide interacts with CFTR to exert both stimulatory and inhibitory effects on
      the channel function. The NEG2 peptide with sequence scrambled to remove helical
      tendencies also inhibits channel function, but does not stimulate. Similar
      results are found for a NEG2 peptide whose helical structure is disrupted by a
      proline residue. When six of the negatively charged carboxylic acid residues are
      replaced by their cognate amides, reducing net negative charge to B3, but
      increasing helical propensity as assessed by circular dichroism, the peptide
      stimulates CFTR channel function, but does not inhibit. We speculate that the
      NEG2 region interacts with other cytosolic domains of CFTR to control opening and
      closing transitions of the chloride channel.

PMID- 11950845
TI  - ErbB-beta-catenin complexes are associated with human infiltrating ductal breast
      and murine mammary tumor virus (MMTV)-Wnt-1 and MMTV-c-Neu transgenic carcinomas.
AB  - Simultaneous deregulation of both Wnt and ErbB growth factors has previously been
      shown to result in the cooperative induction of mammary gland tumors. Using the
      murine mammary tumor virus (MMTV)-Wnt-1 transgenic model of mammary carcinoma, we
      have identified an unvarying association between beta-catenin and epidermal
      growth factor receptor/c-Neu (ErbB1/ErbB2) heterodimers in mammary gland tumors,
      indicating a requirement for ErbB signaling in Wnt-mediated tumorigenesis.
      Expansion of these observations to a second transgenic model, MMTV-c-Neu,
      demonstrated similar tumor-specific interactions, including an ErbB1 ligand
      inducible phosphorylation of both beta-catenin and c-Neu. Direct relevance of
      these findings to human breast cancer was established upon examination of a set
      of human infiltrating ductal breast adenocarcinoma and lymph node metastasis
      tissues taken at surgery. These data revealed increased levels of beta-catenin in
      tumors and metastases versus normal breast as well as an association between beta
      catenin and c-Neu that measurably occurs only in neoplasia, most strongly in
      metastatic lesions. These studies have identified a seemingly indispensable
      interaction between beta-catenin and epidermal growth factor receptor/c-Neu
      heterodimers in Wnt-1-mediated breast tumorigenesis that may indicate a
      fundamental signaling event in human metastatic progression.

PMID- 11950846
TI  - A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable
      enterotoxin receptor.
AB  - Secretory diarrhea is the leading cause of infectious diarrhea in humans.
      Secretory diarrhea may be caused by binding of heat-stable enterotoxins to the
      intestinal receptor guanylyl cyclase C (GCC). Activation of GCC catalyzes the
      formation of cGMP, initiating a signaling cascade that opens the cystic fibrosis
      transmembrane conductance regulator chloride channel at the apical cell surface.
      To identify proteins that regulate the trafficking or function of GCC, we used
      the unique COOH terminus of GCC as the "bait" to screen a human intestinal yeast
      two-hybrid library. We identified a novel protein, IKEPP (intestinal and kidney
      enriched PDZ protein) that associates with the COOH terminus of GCC in
      biochemical assays and by co-immunoprecipitation. IKEPP is expressed in the
      intestinal epithelium, where it is preferentially accumulated at the apical
      surface. The GCC-IKEPP interaction is not required for the efficient targeting of
      GCC to the apical cell surface. Rather, the association with IKEPP significantly
      inhibits heat-stable enterotoxin-mediated activation of GCC. Our findings are the
      first to identify a regulatory protein that associates with GCC to modulate the
      catalytic activity of the enzyme and provides new insights in mechanisms that
      regulate GCC activity in response to bacterial toxin.

PMID- 11950847
TI  - Helical apolipoproteins stabilize ATP-binding cassette transporter A1 by
      protecting it from thiol protease-mediated degradation.
AB  - ATP-binding cassette transporter (ABC) A1 was increased by apolipoprotein A-I
      without an increase of its message in THP-1 cells. The pulse label study
      demonstrated that apoA-I retarded degradation of ABCA1. Similar changes were
      demonstrated by apoA-II, but the effect of high density lipoprotein was almost
      negligible on the basis of equivalent protein concentration. Thiol protease
      inhibitors (leupeptin and N-acetyl-Leu-Leu-norleucinal (ALLN)) increased ABCA1
      and slowed its decay in the cells, whereas none of the proteosome-specific
      inhibitor lactacystin, other protease inhibitors, or the lysosomal inhibitor
      NH(4)Cl showed such effects. The effects of apoA-I and ALLN were additive for the
      increase of ABCA1, and the apoA-I-mediated cellular lipid release was enhanced by
      ALLN. The data suggest that ABCA1 is rapidly degraded by a thiol protease(s) in
      the cells unless helical apolipoproteins in their lipid-free form stabilize ABCA1
      by protecting it from protease-mediated degradation.

PMID- 11950850
TI  - Assessing epidemiological evidence for the teratogenic effects of anticonvulsant
      medications.

PMID- 11950851
TI  - The teratogenicity of anticonvulsant drugs: a progress report.

PMID- 11950852
TI  - Antiepileptic drug therapy during pregnancy: the neurologist's perspective.

PMID- 11950853
TI  - Long term health and neurodevelopment in children exposed to antiepileptic drugs
      before birth.
AB  - OBJECTIVE: To investigate the frequency of neonatal and later childhood morbidity
      in children exposed to antiepileptic drugs in utero. DESIGN: Retrospective
      population based study. SETTING: Population of the Grampian region of Scotland.
      PARTICIPANTS: Mothers taking antiepileptic drugs in pregnancy between 1976 and
      2000 were ascertained from hospital obstetric records and 149 (58% of those
      eligible) took part. They had 293 children whose health and neurodevelopment were
      assessed. MAIN OUTCOME MEASURES: Frequencies of neonatal withdrawal, congenital
      malformations, childhood onset medical problems, developmental delay, and
      behaviour disorders. RESULTS: Neonatal withdrawal was seen in 20% of those
      exposed to antiepileptic drugs. Congenital malformations occurred in 14% of
      exposed pregnancies, compared with 5% of non-exposed sibs, and developmental
      delay in 24% of exposed children, compared with 11% of non-exposed sibs. After
      excluding cases with a family history of developmental delay, 19% of exposed
      children and 3% of non-exposed sibs had developmental delay, 31% of exposed
      children had either major malformations or developmental delay, 52% of exposed
      children had facial dysmorphism compared with 25% of those not exposed, 31% of
      exposed children had childhood medical problems (13% of non-exposed sibs), and
      20% had behaviour disorders (5% of non-exposed). CONCLUSION: Prenatal
      antiepileptic drug exposure in the setting of maternal epilepsy is associated
      with developmental delay and later childhood morbidity in addition to congenital
      malformation.

PMID- 11950855
TI  - Specific haplotypes of the RET proto-oncogene are over-represented in patients
      with sporadic papillary thyroid carcinoma.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC), which may be sporadic (95%) or
      familial (5%), has a prevalence adjusted for age in the general population of
      1:100 000. Somatic rearrangements of the RET proto-oncogene are present in up to
      66% of sporadic tumours, while they are rarely found in familial cases. PURPOSE:
      In order to determine if some variants of this gene, or a combination of them,
      might predispose to PTC, we looked for an association of RET haplotype(s) in PTC
      cases and in controls from four countries matched for sex, age, and population.
      METHODS: Four single nucleotide polymorphisms (SNPs) across the RET coding
      sequence were typed and haplotype frequencies were estimated. Genotype and
      haplotype distributions were compared among these cases and controls. RESULTS:
      Ten haplotypes were observed, the seven most frequent of which have been
      previously described in sporadic Hirschsprung patients and controls. The single
      locus analyses suggested association of exon 2 and exon 13 SNPs with sporadic
      PTC. The haplotype analysis showed over-representation of one haplotype in French
      and Italian sporadic PTC, whereas a different haplotype was significantly under
      represented in French familial PTC. CONCLUSIONS: Our data suggest that some
      variants of RET and some specific haplotypes may act as low penetrance alleles in
      the predisposition to PTC.

PMID- 11950857
TI  - Identification of mutations in the gene encoding sterol regulatory element
      binding protein (SREBP)-2 in hypercholesterolaemic subjects.
AB  - Human cells maintain their cholesterol homeostasis by regulated cleavage of
      membrane bound transcription factors, so-called sterol regulatory element binding
      proteins (SREBPs). If cells are deprived of cholesterol, SREBPs are cleaved by
      two proteolytic steps. The NH2-terminal domain of the SREBPs is released from the
      membranes of the endoplasmic reticulum and transported into the nucleus, where it
      binds to specific nucleotide sequences in the promoters of the low density
      lipoprotein receptor gene and of key genes involved in cholesterol and
      triglyceride homeostasis. Given the central role of SREBPs in the regulation of
      cholesterol metabolism, we investigated whether subjects with inherited forms of
      high plasma cholesterol carry specific sequence variations in SREBP-2 that might
      be involved in the development of hypercholesterolaemia. Exons 5 to 10, encoding
      the DNA binding and the regulatory domains of SREBP-2, were screened for sequence
      variations in a cohort of 70 hypercholesterolaemic subjects. Two missense
      mutations (V623M, R645Q) in the regulatory domain, one single nucleotide
      polymorphism (R371K) in the DNA binding domain, and one translationally silent
      mutation (P433P) were identified in SREBP-2. However, none of the mutations found
      in the regulatory domain could be detected in 167 subjects of a random control
      sample. A potential causative mechanism of these mutations for high plasma
      cholesterol concentrations is discussed. In summary, this is the first report of
      mutations in the human SREBP-2 gene to suggest that these and/or other mutations
      in this key regulator of cholesterol metabolism are associated with
      hypercholesterolaemia.

PMID- 11950856
TI  - Automated fluorescent genotyping detects 10% of cryptic subtelomeric
      rearrangements in idiopathic syndromic mental retardation.
AB  - Recent studies have shown that cryptic unbalanced subtelomeric rearrangements
      contribute to a significant proportion of idiopathic syndromic mental retardation
      cases. Using a fluorescent genotyping based strategy, we found a 10% rate of
      cryptic subtelomeric rearrangements in a large series of 150 probands with severe
      idiopathic syndromic mental retardation and normal RHG-GTG banded karyotype.
      Fourteen children were found to carry deletions or duplications of one or more
      chromosome telomeres and two children had uniparental disomy. This study clearly
      shows that fluorescent genotyping is a sensitive and cost effective method that
      not only detects cryptic subtelomeric rearrangements but also provides a unique
      opportunity to detect uniparental disomies. We suggest giving consideration to
      systematic examination of subtelomeric regions in the diagnostic work up of
      patients with unexplained syndromic mental retardation.

PMID- 11950848
TI  - Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility.
AB  - This review focuses on genes other than the high penetrance genes BRCA1 and BRCA2
      that are involved in breast cancer susceptibility. The goal of this review is the
      discovery of polymorphisms that are either associated with breast cancer or that
      are in strong linkage disequilibrium with breast cancer causing variants. An
      association with breast cancer at a 5% significance level was found for 13
      polymorphisms in 10 genes described in more than one breast cancer study. Our
      data will help focus on the further analysis of genetic polymorphisms in
      populations of appropriate size, and especially on the combinations of such
      polymorphisms. This will facilitate determination of population attributable
      risks, understanding of gene-gene interactions, and improving estimates of
      genetic cancer risks.

PMID- 11950858
TI  - A new MRXS locus maps to the X chromosome pericentromeric region: a new syndrome
      or narrow definition of Sutherland-Haan genetic locus?

PMID- 11950859
TI  - Distinctive audiometric features between USH2A and USH2B subtypes of Usher
      syndrome.

PMID- 11950861
TI  - Identification of cryptic splice site, exon skipping, and novel point mutations
      in type I CD36 deficiency.

PMID- 11950863
TI  - Four novel mutations in the OFD1 (Cxorf5) gene in Finnish patients with oral
      facial-digital syndrome 1.

PMID- 11950860
TI  - Dominant X linked retinitis pigmentosa is frequently accounted for by truncating
      mutations in exon ORF15 of the RPGR gene.

PMID- 11950868
TI  - Chromosome 10p13-14 and 22q11 deletion screening in 100 patients with isolated
      and syndromic conotruncal heart defects.

PMID- 11950865
TI  - Genetic characterisation of patients with multiple colonic polyps.

PMID- 11950869
TI  - Molecular characterisation of a ring chromosome 22 in a patient with severe
      language delay: a contribution to the refinement of the subtelomeric 22q deletion
      syndrome.

PMID- 11950870
TI  - Absence of 22q11 deletions in 211 patients with developmental delay analysed
      using PCR.

PMID- 11950871
TI  - A school based study of children with learning disability indicates poor levels
      of genetic investigation.

PMID- 11950873
TI  - Movie critic corner. By Caveman.

PMID- 11950872
TI  - DTDST mutations are not a frequent cause of idiopathic talipes equinovarus (club
      foot).

PMID- 11950874
TI  - Ankyrins.

PMID- 11950875
TI  - BH3-only proteins - evolutionarily conserved proapoptotic Bcl-2 family members
      essential for initiating programmed cell death.
AB  - The BH3-only members of the Bcl-2 protein family are essential initiators of
      programmed cell death and are required for apoptosis induced by cytotoxic
      stimuli. These proteins have evolved to recognise distinct forms of cell stress.
      In response, they unleash the apoptotic cascade by inactivating the protective
      function of the pro-survival members of the Bcl-2 family and by activating the
      Bax/Bax-like pro-apoptotic family members.

PMID- 11950876
TI  - Extracellular signal regulated kinase (ERK)/mitogen activated protein kinase
      (MAPK)-independent functions of Raf kinases.
AB  - Raf comprises a family of three kinases, A-Raf, B-Raf and Raf-1, which are best
      known as key regulators of the MEK-MAPK/ERK cascade. This module is often
      perceived as a linear pathway in which ERK is the effector. However, recent
      advances have unveiled a role for Raf outside this established signalling unit.
      Current evidence, including gene-knockout studies in mice, suggests that there
      are ERK-independent functions of Raf kinases. Regulation of apoptosis is one area
      in which Raf may function independently of ERK, although its substrates remain to
      be identified. Other studies have suggested that Raf has kinase-independent
      functions and may act as a scaffold protein.

PMID- 11950878
TI  - Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin
      turnover.
AB  - Cofilin-ADF (actin-depolymerizing factor) is an essential driver of actin-based
      motility. We discovered two proteins, p65 and p55, that are components of the
      actin-cofilin complex in a human HEK293 cell extract and identified p55 as
      CAP1/ASP56, a human homologue of yeast CAP/SRV2 (cyclase-associated protein). CAP
      is a bifunctional protein with an N-terminal domain that binds to Ras-responsive
      adenylyl cyclase and a C-terminal domain that inhibits actin polymerization.
      Surprisingly, we found that the N-terminal domain of CAP1, but not the C-terminal
      domain, is responsible for the interaction with the actin-cofilin complex. The N
      terminal domain of CAP1 was also found to accelerate the depolymerization of F
      actin at the pointed end, which was further enhanced in the presence of cofilin
      and/or the C-terminal domain of CAP1. Moreover, CAP1 and its C-terminal domain
      were observed to facilitate filament elongation at the barbed end and to
      stimulate ADP-ATP exchange on G-actin, a process that regenerates easily
      polymerizable G-actin. Although cofilin inhibited the nucleotide exchange on G
      actin even in the presence of the C-terminal domain of CAP1, its N-terminal
      domain relieved this inhibition. Thus, CAP1 plays a key role in speeding up the
      turnover of actin filaments by effectively recycling cofilin and actin and
      through its effect on both ends of actin filament.

PMID- 11950877
TI  - Dissecting interactions between EB1, microtubules and APC in cortical clusters at
      the plasma membrane.
AB  - End-binding protein (EB) 1 binds to the C-terminus of adenomatous polyposis coli
      (APC) protein and to the plus ends of microtubules (MT) and has been implicated
      in the regulation of APC accumulation in cortical clusters at the tip of
      extending membranes. We investigated which APC domains are involved in cluster
      localization and whether binding to EB1 or MTs is essential for APC cluster
      localization. Armadillo repeats of APC that lack EB1- and MT-binding domains are
      necessary and sufficient for APC localization in cortical clusters; an APC
      fragment lacking the armadillo repeats, but containing MT- and EB1-binding
      domains, does not localize to the cortical clusters but instead co-aligns with
      MTs throughout the cell. Significantly, analysis of endogenous proteins reveals
      that EB1 does not accumulate in the APC clusters. However, overexpressed EB1 does
      accumulate in APC clusters; the APC-binding domain in EB1 is located in the C
      terminal region of EB1 between amino acids 134 and 268. Overexpressed APC- or MT
      binding domains of EB1 localize to APC cortical clusters and MT, respectively,
      without affecting APC cluster formation itself. These results show that
      localization of APC in cortical clusters is different from that of EB1 at MT plus
      ends and appears to be independent of EB1.

PMID- 11950879
TI  - Control of localization of a spindle checkpoint protein, Mad2, in fission yeast.
AB  - To ensure accurate chromosome segregation, the spindle checkpoint delays the
      onset of sister chromatid separation when the spindle is not attached to a
      kinetochore. Mad2, a component of the checkpoint, targets fission yeast
      Slp1/budding yeast Cdc20/human p55CDC and prevents it from promoting proteolysis,
      which is a prerequisite to sister chromatid separation. The protein is localized
      to unattached kinetochores in higher eukaryotes, and it is thought to be required
      for activation of the checkpoint as well. In this study, Mad2 and its target Slp1
      were visualized in a tractable organism, fission yeast Schizosaccharomyces pombe.
      When cells were arrested at a prometaphase-like stage, the Mad2-Slp1 complex was
      stable and the two proteins were colocalized to unattached kinetochores. When the
      spindle attachment was completed, the complex was no longer detectable and only
      Mad2 was found associated to the spindle. These results would suggest that
      unattached kinetochores provide sites for assembly of the Mad2-Slp1 complex.
      During interphase, Mad2 was localized to the nuclear periphery as well as to the
      chromatin domain. This localization was abolished in a yeast strain lacking Mad1,
      a protein that physically interacts with Mad2. Mad1 may anchor Mad2 to the
      nuclear membrane and regulate its entry into the nucleus.

PMID- 11950880
TI  - The time course and chromosomal localization of recombination-related proteins at
      meiosis in the mouse are compatible with models that can resolve the early DNA
      DNA interactions without reciprocal recombination.
AB  - During mouse meiosis, the early prophase RAD51/DMC1 recombination protein sites,
      which are associated with the chromosome cores and which serve as markers for
      ongoing DNA-DNA interactions, are in ten-fold excess of the eventual reciprocal
      recombinant events. Most, if not all, of these early interactions are eliminated
      as prophase progresses. The manner in which these sites are eliminated is the
      focus of this investigation. We report that these sites acquire replication
      protein A, RPA and the Escherichia coli MUTS homologue, MSH4p, and somewhat later
      the Bloom helicase, BLM, while simultaneously losing the RAD51/DMC1 component.
      Eventually the RPA component is also lost and BLM sites remain. At that time, the
      MUTL homologue, MLH1p, which is essential for reciprocal recombination in the
      mouse, appears in numbers and locations that correspond to the distribution of
      reciprocal recombination events. However, the MLH1 foci do not appear to coincide
      with the remaining BLM sites. The MLH1p is specifically localized to electron
      microscope-defined recombination nodules. We consider the possibility that the
      homology-search RAD51/DMC1 complexes are involved in homologous chromosome
      synapsis but that most of these early DNA-DNA interactions are later resolved by
      the anti-recombination RPA/MSH4/BLM-topoisomerase complex, thereby preventing the
      formation of superfluous reciprocal recombinant events.

PMID- 11950881
TI  - Remodeling the intercalated disc leads to cardiomyopathy in mice misexpressing
      cadherins in the heart.
AB  - The contractile force of the cardiomyocyte is transmitted through the adherens
      junction, a component of the intercalated disc, enabling the myocardium to
      function as a syncytium. The cadherin family of cell adhesion receptors, located
      in the adherens junction, interact homophilically to mediate strong cell-cell
      adhesion. Ectopic expression of cadherins is associated with changes in tumor
      cell behavior and pathology. To examine the effect of cadherin specificity on
      cardiac structure and function, we expressed either the epithelial cadherin, E
      cadherin, or N-cadherin in the heart of transgenic mice. E-cadherin was localized
      to the intercalated disc structure in these animals similar to endogenous N
      cadherin. Both N- and E-cadherin transgenic animals developed dilated
      cardiomyopathy. However, misexpression of E-cadherin led to earlier onset and
      increased mortality compared with N-cadherin mice. A dramatic decrease in
      connexin 43 was associated with the hypertrophic response in E-cadherin
      transgenic mice. Myofibril organization appeared normal although, vinculin, which
      normally localizes to the intercalated disc, was redistributed to the cytoplasm
      in the E-cadherin transgenic mice. Furthermore, E-cadherin induced cyclin D1,
      nuclear reduplication, and karyokinesis in the absence of cytokinesis, resulting
      in myocytes with two closely opposed nuclei. By contrast, N-cadherin
      overexpressing transgenic mice did not exhibit an increase in cyclin D1,
      suggesting that E-cadherin may provide a specific growth signal to the myocyte.
      This study demonstrates that modulation of cadherin-mediated adhesion can lead to
      dilated cardiomyopathy and that E-cadherin can stimulate DNA replication in
      myocytes normally withdrawn from the cell cycle.

PMID- 11950882
TI  - Novel syntaxin gene sequences from Giardia, Trypanosoma and algae: implications
      for the ancient evolution of the eukaryotic endomembrane system.
AB  - SNAP receptors or SNARES are crucial components of the intracellular membrane
      system of eukaryotes. The syntaxin family of SNAREs have been shown to have roles
      in neurotransmission, vesicular transport, membrane fusion and even internal
      membrane compartment reconstruction. While syntaxins and SNAREs in general have
      been well characterized in mammalian and yeast models, little is known about
      their overall distribution across eukaryotic diversity or about the evolution of
      the syntaxin gene family. By combining bioinformatic, molecular biological and
      phylogenetic approaches, we demonstrate that various syntaxin homologs are not
      only present in 'eukaryotic crown taxa' but across a wide range of eukaryotic
      lineages. The alignment of evolutionarily diverse syntaxin paralogs shows that an
      isoleucine residue critical to nSec1-syntaxin complex formation and the
      characteristic syntaxin glutamine residue are nearly universally conserved,
      implying a general functional importance for these residues. Other identified
      functional residues involved in botulism toxicity and calcium-binding-protein
      interactions are also compared. The presence of Golgi-related syntaxins in the
      intestinal parasite Giardia intestinalis provides further evidence for a cryptic
      Golgi in this 'adictyosomal' taxon, and another likely case of secondary
      reduction in this parasite. The phylogeny of syntaxins shows a number of nested
      duplications, including a case of parallel evolution in the plasma membrane
      associated syntaxins, and ancestral duplications in the other syntaxin paralogs.
      These speak to ancient events in the evolution of the syntaxin system and
      emphasize the universal role of the syntaxins in the eukaryotic intracellular
      compartment system.

PMID- 11950883
TI  - Stem cell factor activates telomerase in mouse mitotic spermatogonia and in
      primordial germ cells.
AB  - The discovery of sterility in the descendants of telomerasenull mutant mice,
      owing to the lack of spermatogonia proliferation, has drawn attention to the role
      of telomerase activity in mouse spermatogenesis. Since spermatogonia
      proliferation is under Kitl control, we explored its possible role in the
      regulation of telomerase activity. We show that Kitl induces telomerase activity
      in mitotic spermatogonia and increases the mRNA levels of both the catalytic
      subunit form and the telomerase RNA template. The increase of telomerase activity
      by Kitl is blocked by the presence of the PI3K inhibitor LY294002. Kit-positive
      proliferating male primordial germ cells (PGCs) show low levels of telomerase
      activity, but they increase telomerase activity upon Kitl stimulation. Diplotene
      arrested growing oocytes that reexpress Kit do not increase telomerase activity
      upon Kitl stimulation. Our data suggest that the induction of telomerase by Kitl
      may contribute to the self-renewing potential of male germ cells and of PGCs.

PMID- 11950884
TI  - Different mechanisms of cell polarisation in vegetative and shmooing growth in
      fission yeast.
AB  - Schizosaccharomyces pombe cells have two polarised growth modes: an intrinsic
      vegetative growth mode, determined by an internal positioning mechanism and an
      extrinsic shmooing growth mode, activated by external pheromone. We have analysed
      the role of the cell end marker Tea1p, the CLIP170 like protein Tip1p, the
      kinesin like protein Tea2p and the Dyrk-like kinase Pom1p, during the switch
      between the two growth patterns, with the intention of studying the switch away
      from the vegetative growth mode. In vegetative growth these morphological factors
      are concentrated at cell ends, whereas during shmooing growth they are
      delocalised from the cell ends. In the absence of Tea1p, Tip1p and Tea2p,
      vegetative cells display microtubule and cell polarisation defects, but shmooing
      cells are indistinguishable from wild-type and shmoo more readily. These results
      suggest that Tea1p, Tip1p and Tea2p are not required for polarised growth during
      shmooing, but form part of the intrinsic vegetative growth mode that needs to be
      dismantled before cells can generate an extrinsic growth patterns. In contrast,
      Pom1p appears to have a role in the initial stages of the switch to the shmooing
      growth mode.

PMID- 11950885
TI  - Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian
      homologs of the transmembrane GTPase Fzo.
AB  - Two human Fzo-homologs, mitofusins Mfn1 and Mfn2, are shown by RT-PCR and western
      blot to be ubiquitous mitochondrial proteins. Protease digestion experiments
      reveal that Mfn2 is an outer membrane protein with N-terminal and C-terminal
      domains exposed towards the cytosol. The transmembrane and C-terminal domains of
      Mfn2 (Mfn2-TMCT) are targeted to mitochondria and deletion of these domains leads
      to the cytosolic localization of truncated Mfn2 (Mfn2-NT). Mfn2 is targeted to
      the endoplasmic reticulum or to mitochondria when the C-terminal domain is
      replaced by short stretches of neutral/hydrophobic (Mfn2-IYFFT) or polar/basic
      (Mfn2-RRD) amino acids. The coiled-coil domains of Mfn2, upstream and downstream
      of the transmembrane domain, are also important for mitochondrial targeting: Mfn2
      mutants deleted of any of its coiled-coil domains are only partially targeted to
      mitochondria and significant protein amounts remain cytosolic. We show that these
      coiled-coil domains interact with each other: mistargeted Mfn2-NT or Mfn2-IYFFT
      localize to mitochondria if co-expressed with Mfn2-TMCT. This relocalization is
      abolished when the coiled-coil domain is deleted in any of the co-transfected
      molecules. We also found that Mfn2 can cluster active mitochondria in the
      perinuclear region independently of the cytoskeleton, bring mitochondrial
      membranes into close contact and modify mitochondrial structure, without
      disturbing the integrity of the inner and outer membrane.

PMID- 11950886
TI  - The importin-beta P446L dominant-negative mutant protein loses RanGTP binding
      ability and blocks the formation of intact nuclear envelope.
AB  - Three of the four independently induced Ketel(D) dominantnegative female sterile
      mutations that identify the Drosophila importin-beta gene, originated from a
      C4114--> T transition and the concurrent replacement of Pro446 by Leu (P446L). CD
      spectroscopy of representative peptides with Pro or Leu in the crucial position
      revealed that upon the Pro-->Leu exchange the P446L mutant protein loses
      flexibility and attains most likely an open conformation. The P446L mutation
      abolishes RanGTP binding of the P446L mutant form of importin-beta protein and
      results in increased RanGDP binding ability. Notably, the P446L mutant importin
      beta does not exert its dominant-negative effect on nuclear protein import and
      has no effect on mitotic spindle-related functions and chromosome segregation.
      However, it interferes with nuclear envelope formation during mitosis-to
      interphase transition, revealing a novel function of importin-beta.

PMID- 11950887
TI  - Trafficking of tail-anchored proteins: transport from the endoplasmic reticulum
      to the plasma membrane and sorting between surface domains in polarised
      epithelial cells.
AB  - Tail-anchored (TA) proteins, which are defined by an N-terminal cytosolic region
      and a C-terminal transmembrane domain (TMD), provide useful models for studying
      the role of the TMD in sorting within the exo-endocytic system. Previous work has
      shown that a short TMD is required to keep ER-resident TA proteins from escaping
      to downstream compartments of the secretory pathway. To investigate the role of
      the TMD in TA protein sorting, we used model constructs, which consisted of GFP
      linked at its C-terminus to the tail region of cytochrome b(5) with TMDs of
      differing length or hydrophobicity. Expression of these constructs in CV-1 cells
      demonstrated that the feature determining exit from the ER is hydrophobicity and
      that if exit occurs, at least a part of the protein reaches the cell surface. To
      investigate which pathway to the surface is followed by plasma-membrane-directed
      TA constructs, we expressed the TA constructs in polarised Madin Darby Canine
      Kidney (MDCK) cells. The constructs with 22 and 25 residue TMDs were localised
      basolaterally, but addition at the C-terminus of a 20-residue peptide containing
      an N-glycosylation site resulted in glycosylation-dependent relocation of
      approximately 50% of the protein to the apical surface. This result suggests that
      TA proteins may reach the basolateral surface without a signal or that our
      constructs contain a weak basolateral determinant that is recessive to the apical
      information carried by the glycan. To assess the effect of the TMDs of endogenous
      TA proteins, GFP was linked to the tails of syntaxin 3 and 4, which localise to
      the apical and basolateral surface, respectively, of MDCK cells. The two GFP
      fusion proteins showed a different surface distribution, which is consistent with
      a role for the two syntaxin TMDs in polarised sorting.

PMID- 11950888
TI  - Sla1p couples the yeast endocytic machinery to proteins regulating actin
      dynamics.
AB  - Sla1p is a protein required for cortical actin patch structure and organisation
      in budding yeast. Here we use a combination of immunofluorescence microscopy and
      biochemical approaches to demonstrate interactions of Sla1p both with proteins
      regulating actin dynamics and with proteins required for endocytosis. Using Sla1p
      binding studies we reveal association of Sla1p with two proteins known to be
      important for activation of the Arp2/3 complex in yeast, Abp1p and the yeast WASP
      homologue Las17p/Bee1p. A recent report of Sla1p association with Pan1p puts
      Sla1p in the currently unique position of being the only yeast protein known to
      interact with all three known Arp2/3-activating proteins in yeast. Localisation
      of Sla1p at the cell cortex is, however, dependent on the EH-domain-containing
      protein End3p, which is part of the yeast endocytic machinery. Using spectral
      variants of GFP on Sla1p (YFP) and on Abp1p (CFP) we show for the first time that
      these proteins can exist in discrete complexes at the cell cortex. However, the
      detection of a significant FRET signal means that these proteins also come close
      together in a single complex, and it is in this larger complex that we propose
      that Sla1p binding to Abp1p and Las17p/Bee1p is able to link actin dynamics to
      the endocytic machinery. Finally, we demonstrate marked defects in both fluid
      phase and receptor-mediated endocytosis in cells that do not express SLA1,
      indicating that Sla1p is central to the requirement in yeast to couple
      endocytosis with the actin cytoskeleton.

PMID- 11950889
TI  - Desmosomes: interconnected calcium-dependent structures of remarkable stability
      with significant integral membrane protein turnover.
AB  - Desmosomes are prominent cell adhesion structures that are major stabilizing
      elements, together with the attached cytoskeletal intermediate filament network,
      of the cytokeratin type in epithelial tissues. To examine desmosome dynamics in
      tightly coupled cells and in situations of decreased adhesion, fluorescent
      desmosomal cadherin desmocollin 2a (Dsc2a) chimeras were stably expressed in
      human hepatocellular carcinoma-derived PLC cells (clone PDc-13) and in Madin
      Darby canine kidney cells (clone MDc-2) for the continuous monitoring of
      desmosomes in living cells. The hybrid polypeptides integrated specifically and
      without disturbance into normal-appearing desmosomes that occurred in association
      with typical cytokeratin filament bundles. Tracking of labeled adhesion sites
      throughout the cell cycle by time-lapse fluorescence microscopy revealed that
      they were immobile and that they maintained their structural integrity for long
      periods of time. Time-space diagrams further showed that desmosomal positioning
      was tightly controlled, even during pronounced cell shape changes, although the
      desmosomal arrays extended and contracted, suggesting that they were
      interconnected by a flexible system with intrinsic elasticity. Double
      fluorescence microscopy detecting Dsc2a chimeras together with fluorescent
      cytokeratin 18 chimeras revealed the association and synchronous movement of
      labeled desmosomes and fluorescent cytokeratin filaments. Only a minor
      destabilization of desmosomes was observed during mitosis, demonstrated by
      increased diffuse plasma membrane fluorescence and the fusion of desmosomes into
      larger structures. Desmosomes did not disappear completely at any time in any
      cell, and residual cytokeratin filaments remained in association with adhesion
      sites throughout cell division. On the other hand, a rapid loss of desmosomes was
      observed upon calcium depletion, with irreversible uptake of some desmosomal
      particles. Simultaneously, diffusely distributed desmosomal cadherins were
      detected in the plasma membrane that retained the competence to nucleate the
      reformation of desmosomes after the cells were returned to a standard calcium
      containing medium. To examine the molecular stability of desmosomes, exchange
      rates of fluorescent chimeras were determined by fluorescence recovery after
      photobleaching, thereby identifying considerable Dsc2a turnover with different
      rates of fluorescence recovery for PDc-13 cells (36+/-17% recovery after 30
      minutes) and MDc-2 cells (60+/-20% recovery after 30 minutes). Taken together,
      our observations suggest that desmosomes are pliable structures capable of fine
      adjustment to functional demands despite their overall structural stability and
      relative immobility.

PMID- 11950890
TI  - Phosphorylation of the myosin regulatory light chain plays a role in motility and
      polarity during Dictyostelium chemotaxis.
AB  - The myosin regulatory light chain (RLC) of Dictyostelium discoideum is
      phosphorylated at a single serine site in response to chemoattractant. To
      investigate the role of the phosphorylation of RLC in both motility and
      chemotaxis, mutants were generated in which the single phosphorylatable serine
      was replaced with a nonphosphorylatable alanine. Several independent clones
      expressing the mutant RLC in the RLC null mutant, mlcR(-), were obtained. These
      S13A mutants were subjected to high resolution computer-assisted motion analysis
      to assess the basic motile behavior of cells in the absence of a chemotatic
      signal, and the chemotactic responsiveness of cells to the spatial, temporal and
      concentration components of natural cAMP waves. In the absence of a cAMP signal,
      mutant cells formed lateral pseudopods less frequently and crawled faster than
      wild-type cells. In a spatial gradient of cAMP, mutant cells chemotaxed more
      efficiently than wild-type cells. In the front of simulated temporal and natural
      waves of cAMP, mutant cells responded normally by suppressing lateral pseudopod
      formation. However, unlike wild-type cells, mutant cells did not lose cellular
      polarity at the peak and in the back of either wave. Since depolarization at the
      peak and in the descending phase of the natural wave is necessary for efficient
      chemotaxis, this deficiency resulted in a decrease in the capacity of S13A mutant
      cells to track natural cAMP waves relayed by wild-type cells, and in the
      fragmentation of streams late in mutant cell aggregation. These results reveal a
      regulatory pathway induced by the peak and back of the chemotactic wave that
      alters RLC phosphorylation and leads to cellular depolarization. We suggest that
      depolarization requires myosin II rearrangement in the cortex facilitated by RLC
      phosphorylation, which increases myosin motor function.

PMID- 11950891
TI  - Robust G1 checkpoint arrest in budding yeast: dependence on DNA damage signaling
      and repair.
AB  - Although most eukaryotes can arrest in G1 after ionizing radiation, the existence
      or significance of a G1 checkpoint in S. cerevisiae has been challenged. Previous
      studies of G1 response to chemical mutagens, X-ray or UV irradiation indicate
      that the delay before replication is transient and may reflect a strong intra-S
      phase checkpoint. We examined the yeast response to double-stranded breaks in G1
      using gamma irradiation. G1 irradiation induces repair foci on chromosome spreads
      and a Rad53 band shift characteristic of activation, which suggest an active DNA
      damage response. Consistent with a G1 arrest, bud emergence, spindle pole
      duplication and DNA replication are each delayed in a dose-dependent manner.
      Sensitivity to mating pheromone is prolonged to over 18 hours when G1 cells are
      lethally gamma or UV irradiated. Strikingly, G1 delay is the predominant response
      to continuous gamma irradiation at a dose that confers no loss of viability but
      delays cell division. Like the G2/M checkpoint, G1 delay is completely dependent
      on both RAD9 and RAD24 epistasis groups but independent of POL(epsilon). Lethally
      irradiated rad9 mutants rapidly exit G1 but perform a slow S phase, whereas rad17
      and rad24 mutants are completely arrest deficient. Distinct from gamma
      irradiation, G1 arrest after UV is RAD14 dependent, suggesting that DNA damage
      processing is required for checkpoint activation. Therefore, as in the yeast G2/M
      checkpoint response, free DNA ends and/or single-stranded DNA are necessary and
      sufficient to induce a bona fide G1 checkpoint arrest.

PMID- 11950892
TI  - The FA2 gene of Chlamydomonas encodes a NIMA family kinase with roles in cell
      cycle progression and microtubule severing during deflagellation.
AB  - The NIMA kinases are one of several families of kinases that participate in
      driving the eukaryotic cell cycle. NIMA-related kinases have been implicated in
      G2/M progression, chromatin condensation and regulation of the centrosome cycle.
      Here we report the identification of a new member of this family, FA2, from
      Chlamydomonas reinhardtii. FA2 was originally discovered in a genetic screen for
      deflagellation-defective mutants. We have previously shown that FA2 is essential
      for basal-body/centriole-associated microtubule severing. We now report that the
      FA2 NIMA-related kinase also plays a role in cell cycle progression in
      Chlamydomonas. This is the first indication that members of the NIMA family might
      exert their effects through the regulation of microtubule severing.

PMID- 11950893
TI  - Nuclear localization of phosphatidylinositol 4-kinase beta.
AB  - Whereas most phosphatidylinositol 4-kinase (PtdIns 4-kinase) activity is
      localized in the cytoplasm, PtdIns 4-kinase activity has also been detected in
      membrane-depleted nuclei of rat liver and mouse NIH 3T3 cells. Here we have
      characterized the PtdIns 4-kinase that is present in nuclei from NIH 3T3 cells.
      Both type II and type III PtdIns 4-kinase activity were observed in the detergent
      insoluble fraction of NIH 3T3 cells. Dissection of this fraction into cytoplasmic
      actin filaments and nuclear lamina-pore complexes revealed that the actin
      filament fraction contains solely type II PtdIns 4-kinase, whereas lamina-pore
      complexes contain type III PtdIns 4-kinase activity. Using specific antibodies,
      the nuclear PtdIns 4-kinase was identified as PtdIns 4-kinase beta. Inhibition of
      nuclear export by leptomycin B resulted in an accumulation of PtdIns 4-kinase
      beta in the nucleus. These data demonstrate that PtdIns 4-kinase beta is present
      in the nuclei of NIH 3T3 fibroblasts, suggesting a specific function for this
      kinase in nuclear processes.

PMID- 11950895
TI  - Cytogenetics and molecular biology of osteosarcoma.

PMID- 11950896
TI  - Overexpression of Polycomb-group gene rae28 in cardiomyocytes does not complement
      abnormal cardiac morphogenesis in mice lacking rae28 but causes dilated
      cardiomyopathy.
AB  - The Polycomb-group genes (PcG) are widely conserved from Drosophila to mammals
      and are required for maintaining positional information during development. The
      rae28 gene (rae28) is a member of the mouse PcG. Mice deficient in rae28 (rae28(
      /-)) demonstrated that rae28 has a role not only in anteroposterior patterning
      but also in cardiac morphogenesis. In this study we generated transgenic mice
      with ubiquitous or cardiomyocyte-specific exogenous rae28 expression. Genetic
      complementation experiments with these transgenic mice showed that ubiquitous
      expression of rae28 could reverse the cardiac anomalies in rae28(-/-), whereas
      cardiomyocyte-specific expression of rae28 could not, suggesting that rae28 is
      involved in cardiac morphogenesis through a noncardiomyocyte pathway.
      Interestingly, however, cardiomyocyte-specific overexpression of rae28 caused
      dilated cardiomyopathy, which was associated with cardiomyocyte apoptosis,
      abnormal myofibrils, and severe heart failure. Cardiac expression of rae28 was
      predominant in the early embryonic stage, whereas that of the other PcG members
      was relatively constitutive. Because rae28 forms multimeric complexes with other
      PcG proteins in the nucleus, it is presumed that constitutive cardiomyocyte
      specific rae28 overexpression impaired authentic PcG functions in the heart.
      rae28-induced dilated cardiomyopathy may thus provide a clue for clarifying the
      direct role of PcG in the maintenance of cardiomyocytes.

PMID- 11950897
TI  - Stable expression of angiopoietin-1 and other markers by cultured pericytes:
      phenotypic similarities to a subpopulation of cells in maturing vessels during
      later stages of angiogenesis in vivo.
AB  - Pericytes have been difficult cells to study because they do not maintain their
      characteristic phenotype in vitro, and they begin to express fibroblast markers
      after only a few days in culture. We now report methods for the isolation,
      purification, culture, and repurification of human dermal pericytes from mixed
      cell populations using an immunoaffinity-magnetic bead approach coupled with the
      3G5 IgM monoclonal antibody that is specific for a pericyte surface ganglioside.
      These purified cells could be expanded in culture, and they maintained their
      pericyte phenotype for up to 8 days. In addition, they strongly expressed
      angiopoietin-1 (Ang-1) but not angiopoietin-2, Tie-1, or Tie-2; in contrast,
      dermal microvascular endothelial cells exhibited a reciprocal expression pattern.
      These findings are important because the close proximity of endothelial cells and
      pericytes has often made it difficult to determine with certainty the specific
      cell type(s) that expressed each of these proteins in situ. Extending our in
      vitro findings to two models of angiogenesis in vivo, we demonstrated a
      subpopulation of Ang-1-expressing cells that appeared in maturing microvessels
      during later stages of cutaneous wound healing and vascular permeability
      factor/vascular endothelial growth factor-induced angiogenesis. Our results
      provide strong evidence that Ang-1 is expressed by pericytes in vitro and in vivo
      and that the role proposed for Ang-1 in vessel maturation in development can be
      extended to vessel maturation after angiogenesis in adult tissues.

PMID- 11950898
TI  - An immunohistochemical study of the distribution of the measles virus receptors,
      CD46 and SLAM, in normal human tissues and subacute sclerosing panencephalitis.
AB  - We have compared the expression of the known measles virus (MV) receptors,
      membrane cofactor protein (CD46) and the signaling lymphocyte-activation molecule
      (SLAM), using immunohistochemistry, in a range of normal peripheral tissues
      (known to be infected by MV) as well as in normal and subacute sclerosing
      panencephalitis (SSPE) brain. To increase our understanding of how these
      receptors could be utilized by wild-type or vaccine strains in vivo, the results
      have been considered with regard to the known route of infection and systemic
      spread of MV. Strong staining for CD46 was observed in endothelial cells lining
      blood vessels and in epithelial cells and tissue macrophages in a wide range of
      peripheral tissues, as well as in Langerhans' and squamous cells in the skin. In
      lymphoid tissues and blood, subsets of cells were positive for SLAM, in
      comparison to CD46, which stained all nucleated cell types. Strong CD46 staining
      was observed on cerebral endothelium throughout the brain and also on ependymal
      cells lining the ventricles and choroid plexus. Comparatively weaker CD46
      staining was observed on subsets of neurons and oligodendrocytes. In SSPE brain
      sections, the areas distant from lesion sites and negative for MV by
      immunocytochemistry showed the same distribution for CD46 as in normal brain.
      However, cells in lesions, positive for MV, were negative for CD46. Normal brain
      showed no staining for SLAM, and in SSPE brain only subsets of leukocytes in
      inflammatory infiltrates were positive. None of the cell types most commonly
      infected by MV show detectable expression of SLAM, whereas CD46 is much more
      widely expressed and could fulfill a receptor function for some wild-type
      strains. In the case of wild-type stains, which are unable to use CD46, a further
      as yet unknown receptor(s) would be necessary to fully explain the pathology of
      MV infection.

PMID- 11950899
TI  - Experimental immune-mediated pancreatitis in neonatally thymectomized mice
      immunized with carbonic anhydrase II and lactoferrin.
AB  - We previously reported that autoantibodies against carbonic anhydrase II and
      lactoferrin are frequently identified in patients with autoimmune-related
      pancreatitis. To clarify the role of carbonic anhydrase II and lactoferrin, we
      created animal models of autoimmune pancreatitis by immunizing neonatally
      thymectomized mice with carbonic anhydrase II and lactoferrin and also by
      transferring immunized spleen cells to nude mice. Neonatally thymectomized BALB/c
      mice were immunized with carbonic anhydrase II or lactoferrin followed by three
      booster injections (n = 10 in each group). We transferred whole, CD4+, or CD8+
      spleen cells prepared from immunized neonatally thymectomized mice to nude mice
      (n = 5 in each group). Gene expression of IFN-gamma and IL-4 was investigated
      using semiquantitative reverse transcription-polymerase chain reaction. Terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining was
      used to examine apoptosis. In immunized neonatally thymectomized mice, the
      prevalence of inflammation was significantly higher in the pancreas. Inflammation
      was present in all mice receiving whole or CD4+ cells. There was no change in any
      of the mice receiving CD8+ cells or nonimmunized spleen cells. Carbonic anhydrase
      II or lactoferrin-immunized mice had apoptotic duct cells or acinar cells,
      respectively. Expression of the IFN-gamma gene was up-regulated in each group.
      Similar findings were observed in the salivary glands and liver. An immunologic
      mechanism against carbonic anhydrase II or lactoferrin is involved in the
      pathogenesis of these pancreatitis models, in which the effector cells are Th1
      type CD4+ T cells.

PMID- 11950900
TI  - Cell-specific nitric oxide synthase-isoenzyme expression and regulation in
      response to endotoxin in intact rat lungs.
AB  - Nitric oxide (NO) produced by NO synthase (NOS) serves as a ubiquitous mediator
      molecule involved in many physiologic lung functions, including regulation of
      vascular and bronchial tone, immunocompetence, and neuronal signaling. On the
      other hand, excessive and inappropriate NO synthesis in inflammation and sepsis
      has been implicated in vascular abnormalities and cell injury. At least three
      different NOS isoforms (neuronal/brain [bNOS], inducible [iNOS], and endothelial
      [eNOS]) have been described, which are all expressed in normal lung tissue. We
      investigated the cell-specific expression of bNOS, iNOS, and eNOS in perfused
      control rat lungs and lungs undergoing stimulation with endotoxin in the presence
      and absence of plasma constituents. Lung immunohistochemistry and quantitative
      evaluation of staining intensity showed endotoxin-induced increase in iNOS
      expression in particular in bronchial epithelial cells, cells of the bronchus
      associated lymphoid tissue (BALT), alveolar macrophages, and vascular smooth
      muscle cells in a time- and dose-dependent fashion. In endothelial cells, which
      did not express iNOS at baseline, newly induced iNOS was found in response to
      endotoxin. In contrast, expression of eNOS was markedly suppressed under
      endotoxin challenge, particularly in bronchial epithelium, BALT, and alveolar
      macrophages but also in vascular smooth muscle cells and endothelial cells. eNOS
      expression in bronchial smooth muscle cells was not altered. In contrast to iNOS
      and eNOS, cellular expression of bNOS in epithelial cells, nerve fibers, BALT,
      and endothelial cells did not change in response to endotoxin. All changes in NOS
      regulation were found to be independent of plasma constituents. We conclude that
      endotoxin exerts a profound impact on the cell-specific NOS regulation in a large
      number of lung cell types. Prominent features include de novo synthesis or up
      regulation of iNOS, in contrast to down-regulation of eNOS, which may well
      contribute to vascular abnormalities, inflammatory sequelae, and loss of
      physiologic functions in septic lung failure.

PMID- 11950901
TI  - Toward efficient analysis of mutations in single cells from ethanol-fixed,
      paraffin-embedded, and immunohistochemically stained tissues.
AB  - Only a few studies have demonstrated successful molecular analysis after whole
      genome amplification using single cells dissected from paraffin-embedded tissues.
      The results in these studies were limited by low-amplification efficiency and
      high rates of allele dropout. In the present study, the amplification rate using
      a thoroughly modified primer extension and preamplification-PCR protocol was
      improved significantly for single cells microdissected from paraffin-embedded and
      immunohistochemically stained tissues. Tissue fixation with ethanol (85%) and the
      addition of 0.2 mmol/L EDTA helped to achieve an amplification rate between 67%
      (segments 200 to 400 bp) and 72% (segments <200 bp). Normal tissue sections were
      immunohistochemically double stained for overabundance of p53 protein and
      proliferating cell nuclear antigen. Microdissection of single cells was performed
      with a manual micromanipulator equipped with a Tungsten needle. Sequence analysis
      of the TP53 gene was performed after improved primer extension preamplification
      PCR and multiplex PCR from single microdissected cells. The rate of allele
      dropout was at least 68%. These technical advances facilitate routine mutation
      analysis using a single cell or a few cells microdissected from routinely
      processed paraffin-embedded normal and tumor tissues. Allele dropout still
      represents a serious problem in single-cell mutation analysis, especially in
      samples with limited template DNA and prone to DNA damage.

PMID- 11950902
TI  - CD4(+) T-lymphocytes regulate airway remodeling and hyper-reactivity in a mouse
      model of chronic asthma.
AB  - Asthma is an acute-on-chronic inflammatory disease of the airways, characterized
      by airflow obstruction and hyper-reactivity of the airways to a variety of
      stimuli. Chronic asthma is associated with remodeling of the airway wall, which
      may contribute to hyper-reactivity and fixed airflow obstruction. We used an
      improved mouse model of chronic asthma to investigate the role of CD4(+) T
      lymphocytes in airway remodeling and hyper-reactivity. Animals functionally
      depleted of CD4(+) T-lymphocytes by repeated administration of a monoclonal
      antibody exhibited markedly decreased airway responsiveness. In addition, these
      mice had greatly diminished subepithelial fibrosis, epithelial thickening, and
      mucous cell hyperplasia/metaplasia. Chronic inflammation in the airway wall was
      moderately reduced, with a marked decrease in the accumulation of immunoglobulin
      synthesizing plasma cells. However, intraepithelial accumulation of eosinophils
      was not significantly inhibited and airway epithelial expression of eotaxin was
      undiminished. This work provides the first experimental evidence that CD4(+) T
      lymphocytes play a crucial role in the pathogenesis of the lesions of chronic
      asthma and lends support to the notion that functional inhibition of these cells
      may be an important therapeutic target.

PMID- 11950903
TI  - Inhibition by prostaglandin E(2) of anaphylatoxin C5a- but not zymosan-induced
      prostanoid release from rat Kupffer cells.
AB  - The proinflammatory anaphylatoxin C5a induces the release of prostanoids, ie,
      prostaglandins (PG) and thromboxane (TX), from the resident liver macrophages
      (Kupffer cells [KC]). Because KC themselves express prostanoid receptors,
      prostanoids--besides having paracrine functions--might regulate their own release
      in an autocrine loop. So far, such a possible feedback regulation has not been
      investigated systematically, probably because of methodological difficulties to
      measure newly synthesized prostanoids in the presence of added prostanoids. Here,
      after prelabeling of phospholipids with [(14)C]arachidonate, cellularly formed
      [(14)C]prostanoids were determined in the presence of added unlabelled
      prostanoids by thin layer chromatography. In cultured KC, recombinant rat C5a
      (rrC5a) rapidly increased PGD(2), PGE(2), and TXA(2) release, which was strongly
      reduced by PGE(2), but neither by PGD(2) nor by the TXA(2) analog U46619. The
      inhibitory effect of PGE(2) was mimicked by cAMP, indicating that the G(s)
      coupled PGE(2) receptors type 2 or 4 were involved. Zymosan also enhanced
      prostanoid release from KC, but with slightly slower kinetics; this action was
      neither inhibited by PGE(2) nor by cAMP. Also in perfused rat livers, rrC5a
      enhanced prostanoid release from KC as shown by prostanoid overflow and thereby
      indirectly increased glucose output from hepatocytes. Again, PGE(2), but not
      PGD(2), inhibited rrC5a-elicited prostanoid overflow. This resulted in a complete
      inhibition of rrC5a-induced, prostanoid-mediated glucose output. Thus, PGE(2) can
      inhibit specifically the C5a-induced prostanoid release from KC via a feedback
      mechanism and thereby limit prostanoid-mediated hepatocellular defense reactions,
      eg, glucose release.

PMID- 11950905
TI  - The inhibitory effect of CD46, CD55, and CD59 on complement activation after
      immunotherapeutic treatment of cervical carcinoma cells with monoclonal
      antibodies or bispecific monoclonal antibodies.
AB  - The role of membrane-bound complement regulatory proteins (mCRP) in the
      protection of tumor cells in vivo against elimination by the immune system is
      still unknown. In this study the effect of expression of these mCRP by cervical
      cancer cells was investigated. In situ expression of mCRP was observed on
      cervical carcinomas, normal cervical epithelial cells, and the surrounding
      stroma. Deposition of C3 and C5b-9 was sporadically found on the tumor cells and
      the surrounding stroma. A low expression of CD46 was statistically significantly
      associated with deposition of C3. Comparable expression patterns were shown on
      primary cervical tumor cell suspensions. A relatively high deposition of C4c was
      found on these tumor cells, indicating classical pathway activation. Furthermore,
      it was demonstrated that CD55 and CD59 were the most potent inhibitors of C3
      deposition and classical pathway-mediated lysis, respectively, on cervical cancer
      cell lines. The feasibility of increasing complement activation at the tumor cell
      membrane surface was demonstrated with an anti-HLA Class I*anti-CD55 bispecific
      mAb. The potential immunotherapeutic applicability was investigated with both
      anti-G250*anti-CD55 and anti-Ep-CAM*anti-CD55 bispecific mAbs. An approximate 2
      fold increase in C3 deposition, compared with the parental anti-Ep-CAM mAb, was
      attained with an anti-Ep-CAM*anti-CD55 bispecific mAb when the tumor-associated
      antigen was expressed in sufficient amounts. These results demonstrate that when
      tumor-associated antigens are expressed in adequate amounts, bispecific mAbs in
      vivo may be potent immunotherapeutic agents to enhance an inflammatory reaction
      at the tumor site.

PMID- 11950904
TI  - Design of a variant of vascular endothelial growth factor-A (VEGF-A) antagonizing
      KDR/Flk-1 and Flt-1.
AB  - Because of its central role in pathological angiogenesis, vascular endothelial
      growth factor (VEGF) has become a major target for anti-angiogenic therapies. We
      report here the construction of a heterodimeric antagonistic VEGF variant (HD
      VEGF). In this antagonist, binding domains for the VEGF-receptors KDR/Flk-1 and
      Flt-1 are present at one pole of the dimer, whereas the other pole carries domain
      swap mutations, which prevent binding to either receptor. As HD-VEGF can only
      bind to monomeric receptors, it does not lead to signal transduction. Moreover,
      it antagonizes VEGF and possibly other members of the VEGF family, which are
      KDR/Flk-1 and Flt-1 ligands. We show here that HD-VEGF is a potent inhibitor of
      VEGF-mediated proliferation and tissue factor induction in endothelial cell
      cultures, requiring only a 20-fold and a 4-fold excess, respectively, to block
      the activity of wtVEGF completely. A 4-fold excess of HD-VEGF over wtVEGF was
      also sufficient to abrogate vascular permeability as determined in the Miles
      assay in vivo. Furthermore, HD-VEGF inhibited fetal bone angiogenesis in an ex
      vivo assay. Thus, HD-VEGF blocks KDR- and Flt-1-mediated VEGF activities that are
      crucial in the angiogenic process and is therefore a promising, multipotent
      compound in the treatment of angiogenesis-related diseases.

PMID- 11950906
TI  - Eotaxin expression by epithelial cells and plasma cells in chronic asthma.
AB  - Chemoattractants such as eotaxin are believed to play an important role in the
      recruitment of eosinophils into the airways in asthma. We investigated expression
      of eotaxin in the airway wall in a model of chronic human asthma, in which
      systemically sensitized mice were exposed to low mass concentrations of
      aerosolized antigen for 6 weeks. In these animals, the number of intraepithelial
      eosinophils in the airways was significantly increased 3 hours after exposure and
      declined by 24 hours. In parallel, immunoreactivity for eotaxin was strikingly up
      regulated in airway epithelial cells and in inflammatory cells in the lamina
      propria. The latter were identified as plasma cells by double immunofluorescent
      labeling. Increased expression of eotaxin by epithelial cells and plasma cells
      was also demonstrated in a case of fatal human asthma. In contrast, sensitized
      mice that received a single exposure to a high mass concentration of aerosolized
      antigen exhibited delayed eosinophil recruitment, which did not correlate with
      eotaxin expression. Furthermore, in sensitized chronically exposed interleukin-13
      deficient mice there was virtually no recruitment of eosinophils into the
      airways, although eotaxin expression was greater than or equal to that in wild
      type mice. These results indicate that there are striking differences between
      acute and chronic exposure models in the time course of eotaxin expression and
      eosinophil recruitment. Although high eotaxin levels alone are not sufficient to
      cause recruitment of eosinophils into the airways, recurrent exposure may
      generate or up-regulate additional signals required for eosinophil chemotaxis.

PMID- 11950907
TI  - Involvement of dipeptidyl peptidase IV in immune complex-mediated
      glomerulonephritis.
AB  - Dipeptidyl peptidase IV (DPPIV) is widely expressed in many tissues; however, its
      precise biological function is poorly understood. One of its possible physiologic
      roles is an involvement in the immune system, which plays a pivotal role in the
      pathogenesis of glomerulonephritis. The present study focused on the involvement
      of DPPIV in immune complex-mediated glomerulonephritis. Experimental nephritis
      was induced by anti-Thy-1.1 monoclonal antibody E30 using Wistar or F344 rats.
      The application of a new monoclonal antibody against DPPIV, F16, completely
      suppressed E30-induced proteinuria and mesangial proliferation in Wistar rats,
      whereas these preventive effects of F16 were not observed in F344 rats, which
      spontaneously lack DPPIV protein. Treatment with F16 inhibited glomerular
      deposition of complement C3 and complement C4 after the binding of E30 to the
      mesangial cell surface. Because the preventive effect of F16 was attributable to
      suppression of the complement cascade, we examined its influences on complement
      dependent mesangial cell lysis in vitro. We discovered that the complement
      cascade was markedly inactivated in F16-treated Wistar rat serum but not in F16
      treated F344 rats. These results indicate that DPPIV may play a somewhat crucial
      role in regulating the complement cascade and that inhibition of DPPIV may serve
      as a new target for preventing complement-dependent tissue injury.

PMID- 11950908
TI  - MRP6 (ABCC6) detection in normal human tissues and tumors.

PMID- 11950909
TI  - Markers of proliferative activity are predictors of patient outcome for low-grade
      endometrioid adenocarcinoma but not papillary serous carcinoma of endometrium.
AB  - On the basis of pathogenesis, two types of endometrial cancer can be recognized.
      Type 1 endometrial carcinomas are relatively indolent tumors that develop after
      prolonged estrogen stimulation, on a background of endometrial hyperplasia. Type
      2 endometrial carcinomas are aggressive tumors that are not associated with
      hyperplasia or estrogen excess. The aim of this study is to evaluate the
      prognostic significance of tumor proliferative activity in early-stage
      endometrial cancer by using mitotic index and immunostaining, comparing Type 1
      (endometrioid) and Type 2 (papillary serous carcinoma) tumors. The mitotic index,
      MIB-1, and p53 immunostaining in 39 tumors from patients with low-grade Stage Ia
      or Ib endometrioid adenocarcinoma; as well as 23 tumors from patients with Stage
      I papillary serous carcinoma. In low-grade endometrioid adenocarcinoma, mitotic
      and MIB-1 indices were statistically significant independent prognostic
      indicators (P =.004 and P =.018, respectively), and both were strongly correlated
      with p53 expression (P =.01 and P =.006, respectively). The mean mitotic index
      was 5 mitoses/10 high-power fields, and mean MIB-1 index was 27.5%. There was no
      significant correlation between mitotic or MIB-1 indices and patient outcome or
      p53 expression in papillary serous carcinoma. The mean mitotic index was 31
      mitoses/10 high-power fields, and mean MIB-1 index was 30.5% in these tumors. p53
      expression and proliferative indices are strongly correlated in low-grade
      endometrioid adenocarcinoma. MIB-1 and mitotic indices are independent prognostic
      indicators in these tumors. Papillary serous carcinoma of endometrium is rapidly
      proliferative in tumors even at an early stage, and quantification of
      proliferative activity in these tumors does not allow prediction of patient
      outcome.

PMID- 11950910
TI  - DNA copy number changes in lung adenocarcinoma in younger patients.
AB  - We performed a comparative genomic hybridization study on 25 lung adenocarcinoma
      samples from younger patients (<41 y of age) and compared the results with a
      previous comparative genomic hybridization analysis of lung adenocarcinoma
      samples from older patients (50-81 y of age). Twenty of the 25 tumor samples from
      younger patients had DNA copy number changes. Gains, losses, and high-level
      amplifications were seen more frequently in the specimens from the younger group.
      The most striking difference between the two groups was the high frequency of
      gains and/or high-level amplifications in the long arm of chromosome 20 in the
      samples from the younger patients (14/25, 56%) compared with that in the samples
      from the older patients (2/24, 8%, P <.001). Gains in the long arm of chromosome
      22 and of the chromosomal band 11q13 were also detected significantly more often
      in the younger group. No correlation was found between DNA copy number changes
      and clinical parameters. Our results suggest that amplification of genes in the
      long arm of chromosome 20 may be important in the tumorigenesis of lung
      adenocarcinoma in young adults. Several candidate genes have already been
      described in the long arm of chromosome 20, particularly in breast cancer.

PMID- 11950911
TI  - Interobserver variability in the diagnosis of ulcerative colitis-associated
      dysplasia by telepathology.
AB  - Telepathology (TP) is the practice of remote diagnostic consultation of
      electronically transmitted, static, digitalized images. The diagnostic efficacy
      of TP-based consultation services has not been widely tested. Dysplasia that
      arises in association with chronic ulcerative colitis (CUC) is, at present, the
      most important marker of an increased risk of malignancy in patients with this
      disease. Unfortunately, dysplasia is difficult to diagnose histologically and, as
      a result, suffers from a significant degree of intra- and interobserver
      variability. Furthermore, it is often necessary to obtain expert consultation of
      potential CUC-associated dysplasia cases before treatment. Therefore, the aim of
      this study was to evaluate the utility and interobserver variability of
      diagnosing dysplasia in CUC with the use of TP. Static, electronically
      transmitted, digitalized images of 38 CUC cases with areas considered negative,
      indefinite, or positive for dysplasia (low or high grade) were evaluated
      independently by four gastrointestinal pathologists. All cases were then graded
      by each of the pathologists by light-microscopic examination of the hematoxylin
      and eosin-stained glass slides. The degree of interobserver variability was
      determined by kappa statistics. Overall, there was a fair degree of agreement
      (kappa = 0.4) among the four reviewing pathologists after analysis of the
      digitalized images. The poorest level of agreement was in the indefinite and low
      grade dysplasia categories. Grouping together several diagnostic categories (for
      instance, indefinite and low-grade dysplasia, or low-grade dysplasia and high
      grade dysplasia) had no effect on the overall level of agreement. The degree of
      variability in interpretation of glass slides was slightly better (kappa = 0.43)
      but still remained fair. After reviewing all cases by glass slide analysis, the
      diagnosis was changed in 38% of the slides; in the majority of these, the grade
      of dysplasia was increased. Use of TP for consultation in CUC-associated
      dysplasia has a moderate level of interobserver agreement. Because of a variety
      of technical reasons, diagnoses rendered by evaluation of digitalized images
      tended to be of a lower grade than that observed after a review of the glass
      slides.

PMID- 11950912
TI  - Fas-mediated apoptosis of melanoma cells and infiltrating lymphocytes in human
      malignant melanomas.
AB  - In a rodent system, melanoma cells expressing Fas ligand (FasL) could kill Fas
      positive lymphocytes, suggesting that FasL expression was an essential factor for
      melanoma cell survival in vivo. These findings led us to investigate apoptosis,
      and to histochemically analyze involvement of Fas and FasL in the induction of
      apoptosis, in human malignant melanoma tissues. The percentages of terminal
      deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labeling (TUNEL)
      positive melanoma cells and of proliferating cell nuclear antigen (PCNA)-positive
      melanoma cells in melanoma tissues (n = 22) were greater than those in
      melanocytes in uninvolved skin (n = 6) and nevus cells in nevi tissues (n = 9).
      The infiltrating lymphocytes around melanomas were also TUNEL positive.
      Immunohistochemistry revealed expression of Fas and FasL in melanoma cells and
      lymphocytes, whereas no Fas or FasL expression was detected in normal skin
      melanocytes and nevus cells. There was significant correlation between Fas
      positive indices and TUNEL indices in melanoma tissues. Moreover, TUNEL-, Fas-,
      and FasL-positive indices of melanoma cells from patients with Stage 3 melanomas
      were significantly lower than those with Stage 2 melanomas. The PCNA index of
      Stage 1 melanoma was significantly lower than that of the other stages, although
      the difference of PCNA index was insignificant among Stages 2 to 4. Among Stages
      1 to 4, there was no difference in the PCNA, TUNEL-, and Fas-positive indices of
      lymphocytes, although the FasL-positive index of lymphocytes from Stage 3
      melanomas was significantly lower than in that from Stage 2. These data reveal
      that melanoma cells and infiltrating lymphocytes have the potential to induce
      their own apoptosis regulated by Fas and FasL in an autocrine and/or paracrine
      fashion and that the decline of Fas-mediated apoptosis of melanoma cells, rather
      than the apoptosis of infiltrating lymphocytes, may affect the prognosis of
      melanoma patients, possibly through the accumulation of more aberrant cells
      acquiring metastatic activity.

PMID- 11950913
TI  - Availability of CD10 immunohistochemistry as a marker of breast myoepithelial
      cells on paraffin sections.
AB  - CD10, also called common acute lymphoblastic leukemia antigen (CALLA), was
      recently found to be expressed in nonhematopoietic tissues. Although CD10 was
      also identified in human breast myoepithelial cells, its availability of
      immunohistochemistry on paraffin sections has not been examined so far. In the
      present study, we demonstrated CD10 immunohistochemically on paraffin sections of
      both normal and pathological breast tissues, comparing its staining patterns to
      those of smooth muscle actin (SMA), which is now commonly used to highlight
      myoepithelium. CD10 was consistently positive in normal breast myoepithelial
      cells. CD10 also clearly highlighted myoepithelial cells in intraductal
      papilloma, adenosis, ductal hyperplasia, fibroadenoma, and phyllodes tumor as
      well as SMA did. In atypical ductal hyperplasia and ductal carcinoma in situ,
      continuous, discontinuous, and totally negative stainings of both CD10 and SMA
      were noted, depending on foci of neoplastic cell nests. However, both stainings
      clearly demonstrated myoepithelial cells of cancerized acini, being useful in
      differentiating lobular cancerization from microinvasion. Because SMA was also
      positive in normal vessels and spindle-shaped stromal cells, CD10, which was
      negative in vessels, was useful in differentiating myoepithelial cells from thin
      vascular wall in intracystic lesions with delicate papillae. Although background
      staining of spindle-shaped stromal cells was also noted in CD10, the positive
      cell number was less, and the signal was weaker than that of SMA. The absence of
      myoepithelial cells in invasive ductal carcinomas was more clearly highlighted by
      CD10 than SMA. We concluded that CD10 could be another useful marker of breast
      myoepithelial cells on paraffin sections. Combination of CD10 and SMA will
      provide more sophisticated information about presence or absence of myoepithelial
      cells in confusing breast lesions.

PMID- 11950914
TI  - The AIDS autopsy spleen: a comparison of the pre-anti-retroviral and highly
      active anti-retroviral therapy eras.
AB  - Pathologic findings attributed to human immunodeficiency virus (HIV) infection
      and acquired immune deficiency syndrome (AIDS) are described in the spleen in
      studies that encompassed the years preceding highly active anti-retroviral
      therapy (HAART). Major findings included white-pulp depletion, hemosiderin
      deposition, spindle cell proliferations, and perivascular hyalinization.
      Infectious and malignant infiltrates were commonly noted and characterized. The
      histopathology of AIDS autopsy spleens since the introduction of protease
      inhibitors has not been studied. Histologic sections from 168 cases of AIDS
      spleens examined at autopsy over a 19-year period (1982-2000) were evaluated for
      significant pathologic findings. Multiple morphologic parameters were recorded,
      including a graded estimation of white-pulp depletion. Significantly less white
      pulp depletion was observed in the 39 HAART-era spleens (1995-2000) compared with
      the 129 spleens from the 1982-1994 patient group (P =.001). The rates of splenic
      involvement by atypical mycobacteria and cytomegalovirus were similar to those in
      the past, although the overall clinical rates of these opportunistic infections
      were found to be decreased. The annual numbers of AIDS autopsies have decreased,
      reflecting a nationwide trend of lower autopsy rates. Increased survival with HIV
      infection and AIDS is now apparent. Protease inhibitors, in conjunction with
      other contemporary therapies, may have contributed to the preservation of white
      pulp observed in the HAART patient group.

PMID- 11950915
TI  - Comparison of multiparameter flow cytometry with cluster analysis and
      immunohistochemistry for the detection of CD10 in diffuse large B-Cell lymphomas.
AB  - CD10 is a critical antigen for the distinction of follicle-center lymphoma from
      other B-cell lymphomas composed of small cells in fine-needle aspiration
      specimens, tissue core biopsies, and bone marrow. In addition, CD10 is expressed
      in a subset of diffuse large B-cell lymphomas (DLBCLs), where it may be an
      adverse prognostic indicator. We have previously demonstrated that CD10
      expression detected by multiparameter flow cytometry (FC) with cluster analysis
      is highly sensitive and specific for follicle-center lymphoma in the differential
      diagnosis of small B-cell lymphomas. In this study, we assessed the utility of
      paraffin section immunohistochemistry (IHC) for CD10 compared with FC in a cohort
      of 50 DLBCLs. IHC for CD10 was technically successful in 47 of the 50 (94%)
      DLBCLs; 3 failed based on lack of internal CD10 reactivity. CD10 was expressed by
      FC in 20 of 47 DLBCLs (43%); CD10 was positive by IHC in 15 of these (75%). All
      27 cases that were CD10(-) by FC were negative by IHC. The level of CD10
      expression by FC in the 5 FC(+)/IHC(-) cases ranged from relatively dim to
      bright. Our results indicate 75% sensitivity and 100% specificity of CD10
      expression by IHC compared with multiparameter FC with cluster analysis and a 6%
      technical failure rate.

PMID- 11950916
TI  - Peripheral T-cell lymphoma mimicking marginal zone B-cell lymphoma.
AB  - Peripheral T-cell lymphoma (PTCL) may assume a variety of histologic and
      cytologic appearances. We describe eight cases of PTCL morphologically simulating
      marginal zone B-cell lymphoma. We reviewed PTCL cases diagnosed in our
      institution between 1990 and 2000 and selected eight cases for study based on the
      following criteria: small-cell morphology with abundant, clear cytoplasm and
      either marginal zone involvement by the neoplastic infiltrate in lymph node
      biopsies or lymphoepithelial lesions in extranodal biopsies. Histologic features
      and ancillary studies were reviewed. Patients included six women and two men with
      a median age of 53 years (range, 35 to 74 years). Six patients were diagnosed
      with primary nodal PTCL, and two presented with primary extranodal disease. The
      original diagnosis was PTCL in only four cases; three cases were diagnosed as
      atypical lymphoid infiltrate, and one case as benign lymphoepithelial lesion.
      Lymph node biopsies revealed partial effacement of the architecture with residual
      follicles surrounded by the neoplastic small cells. Extranodal sites included
      hard palate, tongue, tonsil, and submandibular glands; all but one case
      demonstrated lymphoepithelial lesions. Monoclonality was demonstrated in six of
      eight cases (rearrangement of T-cell receptor gene), and three of eight had an
      aberrant T-cell population by flow cytometry. The differential diagnosis of
      atypical lymphoid infiltrates with morphologic features of marginal zone B-cell
      lymphoma should include PTCL. This uncommon morphological mimicry should be
      recognized, because PTCL is an aggressive disease regardless of morphology and
      should be treated accordingly.

PMID- 11950917
TI  - Differential expression of DNA nonhomologous end-joining proteins Ku70 and Ku80
      in melanoma progression.
AB  - Ku70 and Ku80 heterodimers function as regulatory subunits of the DNA-dependent
      protein kinase and play a very important role in the repairing of DNA double
      strand breaks. Although Ku70 is proposed as a candidate for a tumor suppressor
      gene, not many data are available on Ku70 and Ku80 expression in human tumors.
      The main aim of this study was to investigate the expression of Ku70 and Ku80 in
      the ultraviolet-induced lesions-nevus cell nevi, lentigos maligna, and malignant
      melanomas. Nineteen nevus cell nevi, 23 lentigos maligna, 76 primary melanomas,
      and 31 melanoma metastases were stained immunohistochemically for the presence of
      Ku70 and Ku80 proteins. Ku70 and Ku80 expression was preserved in about 80% of
      nevi, 26% of lentigo maligna, 45% of primary melanomas, and 67% of melanoma
      metastases. Highly significant differences in Ku70 and Ku80 expression were found
      between nevi, lentigo maligna, and melanomas. In Cox regression, Ku70 and Ku80
      were shown to be highly significant influences on patients' prognosis.
      Significant correlations between Ku70 and Ku80 expressions were found in nevi,
      lentigo maligna, and primary melanomas. These correlations were not more present
      in melanoma metastases. To summarize, earlier phases of melanoma progression seem
      to be connected with the loss of expression of Ku proteins. Metastatic spread is
      related to dysregulation of the Ku70 and Ku80 axis.

PMID- 11950918
TI  - Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with
      Kaposi's sarcoma and a subset of angiosarcomas.
AB  - There is controversy over the histogenesis of Kaposi's sarcoma (KS) from
      lymphatic or blood vessel endothelium. D2-40 is a novel monoclonal antibody to an
      Mr 40,000 O-linked sialoglycoprotein that reacts with a fixation-resistant
      epitope on lymphatic endothelium. We sought to establish the selectivity of D2-40
      for lymphatic endothelium in normal tissues and compare its reactivity with the
      expression of the widely used vascular endothelial marker CD31 in a series of 62
      formalin-fixed and paraffin-embedded vascular lesions including KS. In normal
      tissues, D2-40 stained the endothelium of lymphatic channels but not of blood
      vessels, including arteries and capillaries defined by reactivity with the blood
      vessel endothelial marker PAL-E. In our series of vascular lesions, D2-40 stained
      lymphangiomas (10/10), benign tumors of undisputed lymphatic origin, but not
      benign neoplasms or tumorlike lesions of blood vessel origin, including
      hemangiomas (0/10), glomus tumors (0/3), angiolipomas (0/2), pyogenic granulomas
      (0/2), vascular malformations (0/2), hemangiopericytoma (0/1), or
      hemangioendothelioma (0/1). D2-40 stained all cases of cutaneous KS (24/24) at
      all stages of progression, including patch, plaque, and nodular stages,
      supporting the concept that this disease originates from a cell type capable of
      undergoing lymphatic differentiation. D2-40 also stained three of seven
      angiosarcomas, indicating that a subset of these tumors can undergo at least
      partial differentiation along the lymphatic endothelial lineage and could be
      classified as lymphangiosarcomas. In comparison, CD31 was expressed in all benign
      and malignant vascular lesions, except for glomus tumors (0/3) and 5/10
      lymphangiomas, in which staining was absent. We conclude that D2-40 is a new
      selective marker of lymphatic endothelium in normal tissues and vascular lesions
      and is valuable for studying benign and malignant vascular disorders in routinely
      processed tissue specimens.

PMID- 11950919
TI  - Direct correlation between proliferative activity and dysplasia in pancreatic
      intraepithelial neoplasia (PanIN): additional evidence for a recently proposed
      model of progression.
AB  - A growing body of morphological, clinical, and genetic observations suggests a
      progression model for pancreatic ductal adenocarcinoma. In this model, pancreatic
      ducts progress through a series of architectural and cytological changes that
      define degrees of pancreatic intraepithelial neoplasia (PanIN). Expressed in
      dividing cells, Ki-67 has been extensively used as a proliferation marker. Its
      expression in different grades of PanIN has not been well studied. A total of 76
      PanINs from 41 patients were histologically graded according to recently
      established criteria. These PanINs were then immunolabeled with a monoclonal
      antibody against Ki-67 (Mib-1). Normal ducts and invasive ductal adenocarcinomas
      were also labeled with the antibody. In 15 normal ducts, only 0.41% of the
      epithelial cells expressed Ki-67. Ki-67-labeling indices in the increasing grades
      of PanIN were as follows: PanIN-1A, 0.69%; PanIN-1B, 2.33%; PanIN-2, 14.08%; and
      PanIN-3, 22.01%. Fifteen invasive ductal adenonocarcinomas showed an average
      labeling index of 36.99%. The difference in Ki-67 labeling among these groups was
      statistically significant (P <.0005, Kruskal-Wallis test). This pattern of
      proliferation provides additional evidence supporting the recently proposed
      pancreatic progression model. It also correlates well with known molecular
      changes, such as activating point mutations in the K-ras oncogene and the loss of
      DPC4 and p16 gene expression. Ki-67 staining may be useful as an adjunct in the
      diagnosis of precancerous lesions in the pancreas and may provide a reliable way
      to identify lesions at high risk for the subsequent development of infiltrating
      carcinoma.

PMID- 11950920
TI  - Real-Time t(14;18)(q32;q21) PCR assay combined with high-resolution capillary
      electrophoresis: a novel and rapid approach that allows accurate quantitation and
      size determination of bcl-2/JH fusion sequences.
AB  - Follicular lymphoma is characterized by the presence of the t(14;18)(q32;q21)
      chromosomal translocation that juxtaposes the bcl-2 gene at 18q21 with the
      immunoglobulin heavy chain (IgH) locus at 14q32. We have previously shown that
      accurate quantitation of t(14;18)-carrying cells in follicular lymphoma patients
      can be achieved by non-gel-based real-time TaqMan polymerase chain reaction (PCR;
      Applied Biosystems, Foster City, CA). Since our report, several studies have
      demonstrated that real-time PCR is highly sensitive and a reliable tool for
      evaluating treatment effectiveness and for following minimal residual disease in
      follicular lymphoma patients. Unfortunately, currently available real-time PCR
      methods do not determine the size of the amplification product, which is useful
      for excluding contamination and is commonly used as presumptive evidence of
      clonal identity or disparity when multiple samples from the same patient are
      analyzed. We describe a modified real-time PCR assay that rapidly allows accurate
      quantitation and precise determination of the size of the t(14;18) fusion
      sequence without the need for gel electrophoresis. In this assay, a consensus
      immunoglobulin heavy chain-joining region gene (JH) primer labeled at its 5' end
      with the fluorescent dye NED (Applied Biosystems) is included in the real-time
      PCR assay and thus is incorporated into the bcl-2/JH fusion product. The JH-NED
      primer did not interfere with the TaqMan probe fluorescent signal or target
      detection and allowed subsequent amplicon size determination by semiautomated
      high-resolution capillary electrophoresis.

PMID- 11950922
TI  - c-MYC activation in primary and metastatic ductal adenocarcinoma of the pancreas:
      incidence, mechanisms, and clinical significance.
AB  - Amplification and overexpression of c-MYC is a common event in various
      neoplasias. Recently, comparative genomic hybridization (CGH) of primary
      pancreatic adenocarcinomas revealed a distinct high-level amplification of 8q23
      qter, suggesting that c-MYC located on 8q24 may be a candidate oncogene. To
      evaluate the biological significance and prognostic value of c-MYC activation in
      pancreatic carcinoma, we performed interphase fluorescence in situ hybridization
      (FISH) and immunohistochemistry on a series of 69 primary pancreatic
      adenocarcinomas, 19 corresponding lymph node metastases, and 5 pancreatic
      intraductal lesions. Dual color FISH using a probe for c-MYC (8q24) and a
      centromeric probe for chromosome 8 revealed amplification of c-MYC in 32.3% and
      29.4% of primary and metastatic tumors, respectively. Immunostaining identified c
      MYC protein overexpression in 43.5% of primaries and 31.6% of metastases. Low
      concordance between positive FISH and immunostaining (13.4%) suggests multiple
      independent regulatory pathways of c-MYC activation. Statistical evaluation
      revealed significant correlation (alpha = 0.033) between c-MYC protein
      overexpression and histopathological tumor grade but absence of correlation with
      tumor stage or lymph node status. Analysis of pancreatic intraductal lesions
      showed c-MYC amplification and protein overexpression in two of five cases in
      which invasive carcinoma exhibited identical aberrations. We conclude that
      deregulation of c-MYC protein is common in pancreatic cancer and that it may be
      involved in early neoplastic development and progression rather than in
      locoregional spread of invasive cancer.

PMID- 11950921
TI  - Loss of membranous expression of beta-catenin is associated with tumor
      progression in cutaneous melanoma and rarely caused by exon 3 mutations.
AB  - beta-Catenin plays a fundamental role in the regulation of the E-cadherin-catenin
      cell adhesion complex. It also plays a role in the Wnt signaling pathway by
      activating T-cell factor- and lymphoid enhancer factor-regulated gene
      transcription. The level of beta-catenin in cells is tightly controlled in a
      multiprotein complex, and mutations in the glycogen synthase kinase 3beta (GSK
      3beta) phosphorylation sites of the beta-catenin gene (CTNNB1) result in nuclear
      and/or cytoplasmic accumulation of beta-catenin and constitutive transactivation
      of T-cell factor and lymphoid enhancer factor target genes, a mechanism occurring
      in many cancers. Melanoma cell lines may harbor beta-catenin mutations; in vivo,
      however, cellular accumulation of beta-catenin is rarely caused by CTNNB1
      mutations. In our study, 43 primary cutaneous melanoma and 30 metastases were
      screened for CTNNB1 exon 3 mutations by using a denaturing gradient gel
      electrophoresis technique and sequencing. beta-Catenin mutations were found in 2
      primary melanomas and 1 metastatic melanoma and were not correlated with nuclear
      accumulation of beta-catenin in these cases. Cellular expression of beta-catenin
      was evaluated by immunohistochemistry and by reverse polymerase chain reaction
      (RT-PCR) in 80 and 70 cases, respectively. Immunohistochemistry revealed a
      significant loss of membranous beta-catenin staining between the primary and
      metastatic melanomas as well as between radial and vertical growth phase. RT-PCR
      showed a significant inverse correlation between the amount of RNA and the
      proportion of cells with membranous expression of beta-catenin (P =.0015); no
      correlation existed between the amount of RNA and the number of cells with
      nuclear or cytoplasmic expression of beta-catenin. In conclusion, nuclear
      expression of beta-catenin is seen in cutaneous melanoma but, in contrast to the
      case of many other cancers, does not correlate with tumor stage or mutation
      status. A combination of immunohistochemistry and RT-PCR showed that down
      regulation of membranous beta-catenin was associated with an increased amount of
      beta-catenin RNA in primary or metastatic melanoma. Our results suggest that
      posttranslational events, rather than CTNNB1 mutations, are responsible for the
      altered distribution of beta-catenin in cutaneous melanoma.

PMID- 11950923
TI  - Detection of chromosomal aberrations in well-differentiated hepatocellular
      carcinoma by bright-field in situ hybridization.
AB  - Differentiation between well-differentiated hepatocellular carcinoma (HCC) and
      nonmalignant lesions with increased cellular proliferation may be difficult in
      needle biopsies. Based on recurrent chromosome aberrations known for HCC, we
      developed a nonfluorescent in situ hybridization technique that allows
      combination with morphological analysis in bright-field microscopy. Fourteen
      biopsies of HCC and 31 samples of regenerative nodules (n = 10), chronic
      hepatitis (n = 10), fibrosis or cirrhosis of unknown origin (n = 5), focal
      nodular hyperplasia (n = 2), primary biliary cirrhosis (n = 2), steatosis (n =
      1), and adenomatous hyperplasia (n = 1) were analyzed with probes specific for
      the centromeric regions of chromosomes 1, 6, 7, and 8. After microwave
      pretreatment and in situ hybridization, signals were detected using a tyramine
      based system and AEC as substrate. Evaluation of signals was done by conventional
      bright-field microscopy. Using this approach, aberrant counts were seen for at
      least one chromosome in 12/14 cases of HCC. In contrast, none of the nonmalignant
      lesions revealed aberrant counts for any of the chromosomes analyzed. In
      conclusion, this new combination of in situ hybridization and tyramine
      amplification allows fast and reliable evaluation of chromosome aberrations in a
      histomorphological context similar to paraffin immunohistochemistry. Registration
      of imbalances contributes to a reliable differentiation between malignant and
      nonmalignant lesions of the liver.

PMID- 11950924
TI  - Probing the dynamics and functions of aurora B kinase in living cells during
      mitosis and cytokinesis.
AB  - Aurora B is a protein kinase and a chromosomal passenger protein that undergoes
      dynamic redistribution during mitosis. We have probed the mechanism that
      regulates its localization with cells expressing green fluorescent protein (GFP)
      tagged wild-type or mutant aurora B. Aurora B was found at centromeres at
      prophase and persisted until approximately 0.5 min after anaphase onset, when it
      redistributed to the spindle midzone and became concentrated at the equator along
      midzone microtubules. Depolymerization of microtubules inhibited the dissociation
      of aurora B from centromeres at early anaphase and caused the dispersion of
      aurora B from the spindle midzone at late anaphase; however, centromeric
      association during prometaphase was unaffected. Inhibition of CDK1 deactivation
      similarly caused aurora B to remain associated with centromeres during anaphase.
      In contrast, inhibition of the kinase activity of aurora B appeared to have no
      effect on its interactions with centromeres or initial relocation onto midzone
      microtubules. Instead, kinase-inactive aurora B caused abnormal mitosis and
      deactivation of the spindle checkpoint. In addition, midzone microtubule bundles
      became destabilized and aurora B dispersed from the equator. Our results suggest
      that microtubules, CDK1, and the kinase activity each play a distinct role in the
      dynamics and functions of aurora B in dividing cells.

PMID- 11950926
TI  - Cox18p is required for export of the mitochondrially encoded Saccharomyces
      cerevisiae Cox2p C-tail and interacts with Pnt1p and Mss2p in the inner membrane.
AB  - The amino- and carboxy-terminal domains of mitochondrially encoded cytochrome c
      oxidase subunit II (Cox2p) are translocated out of the matrix to the
      intermembrane space. We have carried out a genetic screen to identify components
      required to export the biosynthetic enzyme Arg8p, tethered to the Cox2p C
      terminus by a translational gene fusion inserted into mtDNA. We obtained multiple
      alleles of COX18, PNT1, and MSS2, as well as mutations in CBP1 and PET309.
      Focusing on Cox18p, we found that its activity is required to export the C-tail
      of Cox2p bearing a short C-terminal epitope tag. This is not a consequence of
      reduced membrane potential due to loss of cytochrome oxidase activity because
      Cox2p C-tail export was not blocked in mitochondria lacking Cox4p. Cox18p is not
      required to export the Cox2p N-tail, indicating that these two domains of Cox2p
      are translocated by genetically distinct mechanisms. Cox18p is a mitochondrial
      integral inner membrane protein. The inner membrane proteins Mss2p and Pnt1p both
      coimmunoprecipitate with Cox18p, suggesting that they work together in
      translocation of Cox2p domains, an inference supported by functional interactions
      among the three genes.

PMID- 11950925
TI  - Grx5 is a mitochondrial glutaredoxin required for the activity of iron/sulfur
      enzymes.
AB  - Yeast cells contain a family of three monothiol glutaredoxins: Grx3, 4, and 5.
      Absence of Grx5 leads to constitutive oxidative damage, exacerbating that caused
      by external oxidants. Phenotypic defects associated with the absence of Grx5 are
      suppressed by overexpression of SSQ1 and ISA2, two genes involved in the
      synthesis and assembly of iron/sulfur clusters into proteins. Grx5 localizes at
      the mitochondrial matrix, like other proteins involved in the synthesis of these
      clusters, and the mature form lacks the first 29 amino acids of the translation
      product. Absence of Grx5 causes: 1) iron accumulation in the cell, which in turn
      could promote oxidative damage, and 2) inactivation of enzymes requiring
      iron/sulfur clusters for their activity. Reduction of iron levels in grx5 null
      mutants does not restore the activity of iron/sulfur enzymes, and cell growth
      defects are not suppressed in anaerobiosis or in the presence of disulfide
      reductants. Hence, Grx5 forms part of the mitochondrial machinery involved in the
      synthesis and assembly of iron/sulfur centers.

PMID- 11950927
TI  - The Schizosaccharomyces pombe aurora-related kinase Ark1 interacts with the inner
      centromere protein Pic1 and mediates chromosome segregation and cytokinesis.
AB  - The chromosomal passenger proteins aurora-B, survivin, and inner centromere
      protein (INCENP) have been implicated in coordinating chromosome segregation with
      cell division. This work describes the interplay between aurora, survivin, and
      INCENP orthologs in the fission yeast Schizosaccharomyces pombe and defines their
      roles in regulating chromosome segregation and cytokinesis. We describe the
      cloning and characterization of the aurora-related kinase gene ark1(+),
      demonstrating that it is an essential gene required for sister chromatid
      segregation. Cells lacking Ark1p exhibit the cut phenotype, DNA fragmentation,
      and other defects in chromosome segregation. Overexpression of a kinase-defective
      version of Ark1, Ark1-K147R, inhibits cytokinesis, with cells exhibiting an
      elongated, multiseptate phenotype. Ark1p interacts physically and/or genetically
      with the survivin and INCENP orthologs Bir1p and Pic1p. We identified Pic1p in a
      two-hybrid screen for Ark1-K147R interacting partners and went on to map domains
      in both proteins that mediate their binding. Pic1p residues 925-972 are necessary
      and sufficient for Ark1p binding, which occurs through the kinase domain. As with
      Ark1-K147R, overexpression of Ark1p-binding fragments of Pic1p leads to
      multiseptate phenotypes. We also provide evidence that the dominant-negative
      effect of Ark1-K147R requires Pic1p binding, indicating that the formation of
      Ark1p-Pic1p complexes is required for the execution of cytokinesis.

PMID- 11950928
TI  - Reconstitution and characterization of budding yeast gamma-tubulin complex.
AB  - Nucleation of microtubules is central to assembly of the mitotic spindle, which
      is required for each cell division. gamma-Tubulin is a universal component
      essential for microtubule nucleation from centrosomes. To elucidate the mechanism
      of microtubule nucleation in budding yeast we reconstituted and characterized the
      yeast gamma-tubulin complex (Tub4p complex) produced in insect cells. The
      recombinant complex has the same sedimentation coefficient (11.6 S) as the native
      complex in yeast cell extracts and contains one molecule of Spc97p, one molecule
      of Spc98p, and two molecules of Tub4p. The reconstituted Tub4p complex binds
      preformed microtubules and has a low nucleating activity, allowing us to begin a
      detailed analysis of conditions that enhance this nucleating activity. We tested
      whether binding of the recombinant Tub4p complex to the spindle pole body docking
      protein Spc110p affects its nucleating activity. The solubility of recombinant
      Spc110p in insect cells is improved by coexpression with yeast calmodulin
      (Cmd1p). The Spc110p/Cmd1p complex has a small sedimentation coefficient (4.2 S)
      and a large Stokes radius (14.3 nm), indicative of an elongated structure. The
      Tub4p complex binds Spc110p/Cmd1p via Spc98p and the K(d) for binding is 150 nM.
      The low nucleation activity of the Tub4p complex is not enhanced when it is bound
      to Spc110p/Cmd1p, suggesting that it requires additional components or
      modifications to achieve robust activity. Finally, we report the identification
      of a large 22 S Tub4p complex in yeast extract that contains multimers of Spc97p
      similar to gamma-tubulin ring complexes found in higher eukaryotic cells.

PMID- 11950929
TI  - Yeast genes controlling responses to topogenic signals in a model transmembrane
      protein.
AB  - Yeast protein insertion orientation (PIO) mutants were isolated by selecting for
      growth on sucrose in cells in which the only source of invertase is a C-terminal
      fusion to a transmembrane protein. Only the fraction with an exocellular C
      terminus can be processed to secreted invertase and this fraction is constrained
      to 2-3% by a strong charge difference signal. Identified pio mutants increased
      this to 9-12%. PIO1 is SPF1, encoding a P-type ATPase located in the endoplasmic
      reticulum (ER) or Golgi. spf1-null mutants are modestly sensitive to EGTA.
      Sensitivity is considerably greater in an spf1 pmr1 double mutant, although PIO
      is not further disturbed. Pmr1p is the Golgi Ca(2+) ATPase and Spf1p may be the
      equivalent ER pump. PIO2 is STE24, a metalloprotease anchored in the ER membrane.
      Like Spf1p, Ste24p is expressed in all yeast cell types and belongs to a highly
      conserved protein family. The effects of ste24- and spf1-null mutations on
      invertase secretion are additive, cell generation time is increased 60%, and
      cells become sensitive to cold and to heat shock. Ste24p and Rce1p cleave the C
      AAX bond of farnesylated CAAX box proteins. The closest paralog of SPF1 is
      YOR291w. Neither rce1-null nor yor291w-null mutations affected PIO or the
      phenotype of spf1- or ste24-null mutants. Mutations in PIO3 (unidentified) cause
      a weaker Pio phenotype, enhanced by a null mutation in BMH1, one of two yeast 14
      3-3 proteins.

PMID- 11950930
TI  - VE-cadherin regulates endothelial actin activating Rac and increasing membrane
      association of Tiam.
AB  - Previously published reports support the concept that, besides promoting
      homotypic intercellular adhesion, cadherins may transfer intracellular signals.
      However, the signaling pathways triggered by cadherin clustering and their
      biological significance are still poorly understood. We report herein that
      transfection of VE-cadherin (VEC) cDNA in VEC null endothelial cells induces
      actin rearrangement and increases the number of vinculin positive adhesion
      plaques. VEC expression augments the level of active Rac but decreases active
      Rho. Microinjection of a dominant negative Rac mutant altered stress fiber
      organization, whereas inhibition of Rho was ineffective. VEC expression increased
      protein and mRNA levels of the Rac-specific guanosine exchange factor Tiam-1 and
      induced its localization at intercellular junctions. In addition, in the presence
      of VEC, the amounts of Tiam, Rac, and the Rac effector PAK as well as the level
      of PAK phosphorylation were found increased in the membrane/cytoskeletal
      fraction. These observations are consistent with a role of VEC in localizing Rac
      and its signaling partners in the same membrane compartment, facilitating their
      reciprocal interaction. Through this mechanism VEC may influence the constitutive
      organization of the actin cytoskeleton.

PMID- 11950932
TI  - The spindle pole body protein Cdc11p links Sid4p to the fission yeast septation
      initiation network.
AB  - The Schizosaccharomyces pombe septation initiation network (SIN) signals the
      onset of cell division from the spindle pole body (SPB) and is regulated by the
      small GTPase Spg1p. The localization of SIN components including Spg1p to the SPB
      is required for cytokinesis and is dependent on Sid4p, a constitutive resident of
      SPBs. However, a direct interaction between Sid4p and other members of the SIN
      has not been detected. To understand how Sid4p is linked to other SIN components,
      we have begun to characterize an S. pombe homolog of the Saccharomyces cerevisiae
      SPB protein Nud1p. We have determined that this S. pombe Nud1p homolog
      corresponds to Cdc11p, a previously uncharacterized SIN element. We report that
      Cdc11p is present constitutively at SPBs and that its function appears to be
      required for the localization of all other SIN components to SPBs with the
      exception of Sid4p. The Cdc11p C terminus localizes the protein to SPBs in a
      Sid4p-dependent manner, and we demonstrate a direct Cdc11p-Sid4p interaction. The
      N-terminus of Cdc11p is required for Spg1p binding to SPBs. Our studies indicate
      that Cdc11p provides a physical link between Sid4p and the Spg1p signaling
      pathway.

PMID- 11950931
TI  - Phosphoinositides regulate membrane-dependent actin assembly by latex bead
      phagosomes.
AB  - Actin assembly on membrane surfaces is an elusive process in which several
      phosphoinositides (PIPs) have been implicated. We have reconstituted actin
      assembly using a defined membrane surface, the latex bead phagosome (LBP), and
      shown that the PI(4,5)P(2)-binding proteins ezrin and/or moesin were essential
      for this process (). Here, we provide several lines of evidence that both
      preexisting and newly synthesized PI(4,5)P(2), and probably PI(4)P, are essential
      for phagosomal actin assembly; only these PIPs were routinely synthesized from
      ATP during in vitro actin assembly. Treatment of LBP with phospholipase C or with
      adenosine, an inhibitor of type II PI 4-kinase, as well as preincubation with
      anti-PI(4)P or anti-PI(4,5)P(2) antibodies all inhibited this process.
      Incorporation of extra PI(4)P or PI(4,5)P(2) into the LBP membrane led to a
      fivefold increase in the number of phagosomes that assemble actin. An ezrin
      mutant mutated in the PI(4,5)P(2)-binding sites was less efficient in binding to
      LBPs and in reconstituting actin assembly than wild-type ezrin. Our data show
      that PI 4- and PI 5-kinase, and under some conditions also PI 3-kinase,
      activities are present on LBPs and can be activated by ATP, even in the absence
      of GTP or cytosolic components. However, PI 3-kinase activity is not required for
      actin assembly, because the process was not affected by PI 3-kinase inhibitors.
      We suggest that the ezrin-dependent actin assembly on the LBP membrane may
      require active turnover of D4 and D5 PIPs on the organelle membrane.

PMID- 11950933
TI  - Vav regulates activation of Rac but not Cdc42 during FcgammaR-mediated
      phagocytosis.
AB  - Phagocytosis is the process whereby cells direct the spatially localized,
      receptor-driven engulfment of particulate materials. It proceeds via remodeling
      of the actin cytoskeleton and shares many of the core cytoskeletal components
      involved in adhesion and migration. Small GTPases of the Rho family have been
      widely implicated in coordinating actin dynamics in response to extracellular
      signals and during diverse cellular processes, including phagocytosis, yet the
      mechanisms controlling their recruitment and activation are not known. We show
      herein that in response to ligation of Fc receptors for IgG (FcgammaR), the
      guanine nucleotide exchange factor Vav translocates to nascent phagosomes and
      catalyzes GTP loading on Rac, but not Cdc42. The Vav-induced Rac activation
      proceeds independently of Cdc42 function, suggesting distinct roles for each
      GTPase during engulfment. Moreover, inhibition of Vav exchange activity or of
      Cdc42 activity does not prevent Rac recruitment to sites of particle attachment.
      We conclude that Rac is recruited to Fcgamma membrane receptors in its inactive,
      GDP-bound state and that Vav regulates phagocytosis through subsequent catalysis
      of GDP/GTP exchange on Rac.

PMID- 11950934
TI  - Nonreceptor tyrosine kinase c-Yes interacts with occludin during tight junction
      formation in canine kidney epithelial cells.
AB  - Occludin is an integral membrane protein that is tyrosine phosphorylated when
      localized at tight junctions. When Ca(2+) was depleted from the culture medium,
      occludin tyrosine phosphorylation was diminished from Madin-Darby canine kidney
      epithelial cells in 2 min. This dephosphorylation was correlated with a
      significant reduction in transepithelial electrical resistance (TER), indicating
      a global loss of the tight junction barrier function. Reconstitution of Ca(2+)
      resulted in a robust tyrosine rephosphorylation of occludin that was temporally
      associated with an increase in TER. Moreover, we demonstrate in this study that
      occludin was colocalized with the nonreceptor tyrosine kinase c-Yes at cell
      junction areas and formed an immunoprecipitable complex with c-Yes in vivo. This
      complex dissociated when the cells were incubated in medium without Ca(2+) or
      treated with a c-Yes inhibitor, CGP77675. In the presence of CGP77675 after
      Ca(2+) repletion, occludin tyrosine phosphorylation was completely abolished and
      both tight junction formation and the increase of the TER were inhibited. Our
      study thus provides strong evidence that occludin tyrosine phosphorylation is
      tightly linked to tight junction formation in epithelial cells, and that the
      nonreceptor tyrosine kinase c-Yes is involved in the regulation of this process.

PMID- 11950937
TI  - Localized calcium signals along the cleavage furrow of the Xenopus egg are not
      involved in cytokinesis.
AB  - It has been proposed that a localized calcium (Ca) signal at the growing end of
      the cleavage furrow triggers cleavage furrow formation in large eggs. We have
      examined the possible role of a Ca signal in cleavage furrow formation in the
      Xenopus laevis egg during the first cleavage. We were able to detect two kinds of
      Ca waves along the cleavage furrow. However, the Ca waves appeared after cleavage
      furrow formation in late stages of the first cleavage. In addition, cleavage was
      not affected by injection of dibromoBAPTA or EGTA into the eggs at a
      concentration sufficient to suppress the Ca waves. Furthermore, even smaller
      classes of Ca release such as Ca puffs and Ca blips do not occur at the growing
      end of the cleavage furrow. These observations demonstrate that localized Ca
      signals in the cleavage furrow are not involved in cytokinesis. The two Ca waves
      have unique characteristics. The first wave propagates only in the region of
      newly inserted membrane along the cleavage furrow. On the other hand, the second
      wave propagates along the border of new and old membranes, suggesting that this
      wave might be involved in adhesion between two blastomeres.

PMID- 11950935
TI  - Regulation of Fab1 phosphatidylinositol 3-phosphate 5-kinase pathway by Vac7
      protein and Fig4, a polyphosphoinositide phosphatase family member.
AB  - The Saccharomyces cerevisiae FAB1 gene encodes the sole phosphatidylinositol 3
      phosphate [PtdIns(3)P] 5-kinase responsible for synthesis of the
      polyphosphoinositide PtdIns(3,5)P(2). VAC7 encodes a 128-kDa transmembrane
      protein that localizes to vacuolar membranes. Both vac7 and fab1 null mutants
      have dramatically enlarged vacuoles and cannot grow at elevated temperatures.
      Additionally, vac7Delta mutants have nearly undetectable levels of
      PtdIns(3,5)P(2), suggesting that Vac7 functions to regulate Fab1 kinase activity.
      To test this hypothesis, we isolated a fab1 mutant allele that bypasses the
      requirement for Vac7 in PtdIns(3,5)P(2) production. Expression of this fab1
      allele in vac7Delta mutant cells suppresses the temperature sensitivity, vacuolar
      morphology, and PtdIns(3,5)P(2) defects normally exhibited by vac7Delta mutants.
      We also identified a mutant allele of FIG4, whose gene product contains a Sac1
      polyphosphoinositide phosphatase domain, which suppresses vac7Delta mutant
      phenotypes. Deletion of FIG4 in vac7Delta mutant cells suppresses the temperature
      sensitivity and vacuolar morphology defects, and dramatically restores
      PtdIns(3,5)P(2) levels. These results suggest that generation of PtdIns(3,5)P(2)
      by the Fab1 lipid kinase is regulated by Vac7, whereas turnover of
      PtdIns(3,5)P(2) is mediated in part by the Sac1 polyphosphoinositide phosphatase
      family member Fig4.

PMID- 11950936
TI  - Antigen-stimulated activation of phospholipase D1b by Rac1, ARF6, and PKCalpha in
      RBL-2H3 cells.
AB  - Phospholipase D (PLD) activity can be detected in response to many agonists in
      most cell types; however, the pathway from receptor occupation to enzyme
      activation remains unclear. In vitro PLD1b activity is phosphatidylinositol 4,5
      bisphosphate dependent via an N-terminal PH domain and is stimulated by Rho, ARF,
      and PKC family proteins, combinations of which cooperatively increase this
      activity. Here we provide the first evidence for the in vivo regulation of PLD1b
      at the molecular level. Antigen stimulation of RBL-2H3 cells induces the
      colocalization of PLD1b with Rac1, ARF6, and PKCalpha at the plasma membrane in
      actin-rich structures, simultaneously with cooperatively increasing PLD activity.
      Activation is both specific and direct because dominant negative mutants of Rac1
      and ARF6 inhibit stimulated PLD activity, and surface plasmon resonance reveals
      that the regulatory proteins bind directly and independently to PLD1b. This also
      indicates that PLD1b can concurrently interact with a member from each regulator
      family. Our results show that in contrast to PLD1b's translocation to the plasma
      membrane, PLD activation is phosphatidylinositol 3-kinase dependent. Therefore,
      because inactive, dominant negative GTPases do not activate PLD1b, we propose
      that activation results from phosphatidylinositol 3-kinase-dependent stimulation
      of Rac1, ARF6, and PKCalpha.

PMID- 11950938
TI  - CD9 is associated with leukemia inhibitory factor-mediated maintenance of
      embryonic stem cells.
AB  - Mouse embryonic stem (ES) cells can proliferate indefinitely in an
      undifferentiated state in the presence of leukemia inhibitory factor (LIF), or
      differentiate into all three germ layers upon removal of this factor. To
      determine cellular factors associated with self-renewal of undifferentiated ES
      cells, we used polymerase chain reaction-assisted cDNA subtraction to screen
      genes that are expressed in undifferentiated ES cells and down-regulated after
      incubating these cells in a differentiation medium without LIF for 48 h. The mRNA
      expression of a tetraspanin transmembrane protein, CD9, was high in
      undifferentiated ES cells and decreased shortly after cell differentiation. An
      immunohistochemical analysis confirmed that plasma membrane-associated CD9 was
      expressed in undifferentiated ES cells but low in the differentiated cells.
      Addition of LIF to differentiating ES cells reinduced mRNA expression of CD9, and
      CD9 expression was accompanied with a reappearance of undifferentiated ES cells.
      Furthermore, activation of STAT3 induced the expression of CD9, indicating the
      LIF/STAT3 pathway is critical for maintaining CD9 expression. Finally, addition
      of anti-CD9 antibody blocked ES cell colony formation and reduced cell viability.
      These results indicate that CD9 may play a role in LIF-mediated maintenance of
      undifferentiated ES cells.

PMID- 11950939
TI  - Nup98 is a mobile nucleoporin with transcription-dependent dynamics.
AB  - Nucleoporin 98 (Nup98), a glycine-leucine-phenylalanine-glycine (GLFG) amino acid
      repeat-containing nucleoporin, plays a critical part in nuclear trafficking.
      Injection of antibodies to Nup98 into the nucleus blocks the export of most RNAs.
      Nup98 contains binding sites for several transport factors; however, the
      mechanism by which this nucleoporin functions has remained unclear. Multiple
      subcellular localizations have been suggested for Nup98. Here we show that Nup98
      is indeed found both at the nuclear pore complex and within the nucleus. Inside
      the nucleus, Nup98 associates with a novel nuclear structure that we term the
      GLFG body because the GLFG domain of Nup98 is required for targeting to this
      structure. Photobleaching of green fluorescent protein-Nup98 in living cells
      reveals that Nup98 is mobile and moves between these different localizations. The
      rate of recovery after photobleaching indicates that Nup98 interacts with other,
      less mobile, components in the nucleoplasm. Strikingly, given the previous link
      to nuclear export, the mobility of Nup98 within the nucleus and at the pore is
      dependent on ongoing transcription by RNA polymerases I and II. These data give
      rise to a model in which Nup98 aids in direction of RNAs to the nuclear pore and
      provide the first potential mechanism for the role of a mobile nucleoporin.

PMID- 11950940
TI  - Xenopus Cdc6 performs separate functions in initiating DNA replication.
AB  - Cdc6 performs an essential role in the initiation of eukaryotic DNA replication
      by recruiting the minichromosome maintenance (MCM) complex onto DNA. Using
      immunodepletion/add-back experiments in Xenopus egg extracts, we have determined
      that both Walker A (ATP binding) and Walker B (ATP hydrolysis) motifs of Xenopus
      Cdc6 (Xcdc6) are essential, but have distinct functional roles. Although Walker B
      mutant protein binds chromatin well, Walker A mutant protein binds chromatin
      poorly. Neither Walker A nor Walker B mutant protein, however, load appreciable
      MCM onto DNA. Herein, we provide evidence that Cdc6 functions as a multimer: 1)
      mutant and wild-type Xcdc6 form multimers; 2) either mutant protein is dominant
      negative when added before wild-type Xcdc6, but stimulates DNA replication when
      added simultaneously with wild-type Xcdc6; and 3) the two mutants restore DNA
      replication when added together, in the absence of wild-type Xcdc6. Our findings
      suggest that ATP may play a key regulatory role within this multimer: its binding
      to Cdc6 promotes chromatin association and its hydrolysis facilitates MCM
      loading. Moreover, ATP binding and hydrolysis may occur in trans between Cdc6
      subunits within the complex.

PMID- 11950941
TI  - Bilayered clathrin coats on endosomal vacuoles are involved in protein sorting
      toward lysosomes.
AB  - In many cells endosomal vacuoles show clathrin coats of which the function is
      unknown. Herein, we show that this coat is predominantly present on early
      endosomes and has a characteristic bilayered appearance in the electron
      microscope. By immunoelectron microscopy we show that the coat contains clathrin
      heavy as well as light chain, but lacks the adaptor complexes AP1, AP2, and AP3,
      by which it differs from clathrin coats on endocytic vesicles and recycling
      endosomes. The coat is insensitive to short incubations with brefeldin A, but
      disappears in the presence of the phosphatidylinositol 3-kinase inhibitor
      wortmannin. No association of endosomal coated areas with tracks of tubulin or
      actin was found. By quantitative immunoelectron microscopy, we found that the
      lysosomal-targeted receptors for growth hormone (GHR) and epidermal growth factor
      are concentrated in the coated membrane areas, whereas the recycling transferrin
      receptor is not. In addition, we found that the proteasomal inhibitor MG 132
      induces a redistribution of a truncated GHR (GHR-369) toward recycling vesicles,
      which coincided with a redistribution of endosomal vacuole-associated GHR-369 to
      the noncoated areas of the limiting membrane. Together, these data suggest a role
      for the bilayered clathrin coat on vacuolar endosomes in targeting of proteins to
      lysosomes.

PMID- 11950942
TI  - Regulated disruption of inositol 1,4,5-trisphosphate signaling in Caenorhabditis
      elegans reveals new functions in feeding and embryogenesis.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) is an important second messenger in animal
      cells and is central to a wide range of cellular responses. The major
      intracellular activity of IP(3) is to regulate release of Ca(2+) from
      intracellular stores through IP(3) receptors (IP(3)Rs). We describe a system for
      the transient disruption of IP(3) signaling in the model organism Caenorhabditis
      elegans. The IP(3) binding domain of the C. elegans IP(3)R, ITR-1, was expressed
      from heat shock-induced promoters in live animals. This results in a dominant
      negative effect caused by the overexpressed IP(3) binding domain acting as an
      IP(3) "sponge." Disruption of IP(3) signaling resulted in disrupted defecation, a
      phenotype predicted by previous genetic studies. This approach also identified
      two new IP(3)-mediated processes. First, the up-regulation of pharyngeal pumping
      in response to food is dependent on IP(3) signaling. RNA-mediated interference
      studies and analysis of itr-1 mutants show that this process is also IP(3)R
      dependent. Second, the tissue-specific expression of the dominant-negative
      construct enabled us to circumvent the sterility associated with loss of IP(3)
      signaling through the IP(3)R and thus determine that IP(3)-mediated signaling is
      required for multiple steps in embryogenesis, including cytokinesis and
      gastrulation.

PMID- 11950943
TI  - A phosphorylated cytoplasmic autoantigen, GW182, associates with a unique
      population of human mRNAs within novel cytoplasmic speckles.
AB  - A novel human cellular structure has been identified that contains a unique
      autoimmune antigen and multiple messenger RNAs. This complex was discovered using
      an autoimmune serum from a patient with motor and sensory neuropathy and contains
      a protein of 182 kDa. The gene and cDNA encoding the protein indicated an open
      reading frame with glycine-tryptophan (GW) repeats and a single RNA recognition
      motif. Both the patient's serum and a rabbit serum raised against the recombinant
      GW protein costained discrete cytoplasmic speckles designated as GW bodies (GWBs)
      that do not overlap with the Golgi complex, endosomes, lysosomes, or peroxisomes.
      The mRNAs associated with GW182 represent a clustered set of transcripts that are
      presumed to reside within the GW complexes. We propose that the GW
      ribonucleoprotein complex is involved in the posttranscriptional regulation of
      gene expression by sequestering a specific subset of gene transcripts involved in
      cell growth and homeostasis.

PMID- 11950944
TI  - Disruption of C-terminal cytoplasmic domain of betaPS integrin subunit has
      dominant negative properties in developing Drosophila.
AB  - We have analyzed a set of new and existing strong mutations in the myospheroid
      gene, which encodes the betaPS integrin subunit of Drosophila. In addition to
      missense and other null mutations, three mutants behave as antimorphic alleles,
      indicative of dominant negative properties. Unlike null alleles, the three
      antimorphic mutants are synthetically lethal in double heterozygotes with an
      inflated (alphaPS2) null allele, and they fail to complement very weak, otherwise
      viable alleles of myospheroid. Two of the antimorphs result from identical splice
      site lesions, which create a frameshift in the C-terminal half of the cytoplasmic
      domain of betaPS. The third antimorphic mutation is caused by a stop codon just
      before the cytoplasmic splice site. These mutant betaPS proteins can support cell
      spreading in culture, especially under conditions that appear to promote integrin
      activation. Analyses of developing animals indicate that the dominant negative
      properties are not a result of inefficient surface expression, or simple
      competition between functional and nonfunctional proteins. These data indicate
      that mutations disrupting the C-terminal cytoplasmic domain of integrin beta
      subunits can have dominant negative effects in situ, at normal levels of
      expression, and that this property does not necessarily depend on a specific new
      protein sequence or structure. The results are discussed with respect to similar
      vertebrate beta subunit cytoplasmic mutations.

PMID- 11950945
TI  - Reorientation of mispositioned spindles in short astral microtubule mutant
      spc72Delta is dependent on spindle pole body outer plaque and Kar3 motor protein.
AB  - Nuclear migration and positioning in Saccharomyces cerevisiae depend on long
      astral microtubules emanating from the spindle pole bodies (SPBs). Herein, we
      show by in vivo fluorescence microscopy that cells lacking Spc72, the SPB
      receptor of the cytoplasmic gamma-tubulin complex, can only generate very short
      (<1 microm) and unstable astral microtubules. Consequently, nuclear migration to
      the bud neck and orientation of the anaphase spindle along the mother-bud axis
      are absent in these cells. However, SPC72 deletion is not lethal because
      elongated but misaligned spindles can frequently reorient in mother cells,
      permitting delayed but otherwise correct nuclear segregation. High-resolution
      time-lapse sequences revealed that this spindle reorientation was most likely
      accomplished by cortex interactions of the very short astral microtubules. In
      addition, a set of double mutants suggested that reorientation was dependent on
      the SPB outer plaque and the astral microtubule motor function of Kar3 but not
      Kip2/Kip3/Dhc1, or the cortex components Kar9/Num1. Our observations suggest that
      Spc72 is required for astral microtubule formation at the SPB half-bridge and for
      stabilization of astral microtubules at the SPB outer plaque. In addition, our
      data exclude involvement of Spc72 in spindle formation and elongation functions.

PMID- 11950946
TI  - Dopamine-induced exocytosis of Na,K-ATPase is dependent on activation of protein
      kinase C-epsilon and -delta.
AB  - The purpose of this study was to define mechanisms by which dopamine (DA)
      regulates the Na,K-ATPase in alveolar epithelial type 2 (AT2) cells. The Na,K
      ATPase activity increased by twofold in cells incubated with either 1 microM DA
      or a dopaminergic D(1) agonist, fenoldopam, but not with the dopaminergic D(2)
      agonist quinpirole. The increase in activity paralleled an increase in Na,K
      ATPase alpha1 and beta1 protein abundance in the basolateral membrane (BLM) of
      AT2 cells. This increase in protein abundance was mediated by the exocytosis of
      Na,K-pumps from late endosomal compartments into the BLM. Down-regulation of
      diacylglycerol-sensitive types of protein kinase C (PKC) by pretreatment with
      phorbol 12-myristate 13-acetate or inhibition with bisindolylmaleimide prevented
      the DA-mediated increase in Na,K-ATPase activity and exocytosis of Na,K-pumps to
      the BLM. Preincubation of AT2 cells with either 2-[1-(3-dimethylaminopropyl)-5
      methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide (Go6983), a selective inhibitor of
      PKC-delta, or isozyme-specific inhibitor peptides for PKC-delta or PKC-epsilon
      inhibited the DA-mediated increase in Na,K-ATPase. PKC-delta and PKC-epsilon, but
      not PKC-alpha or -beta, translocated from the cytosol to the membrane fraction
      after exposure to DA. PKC-delta- and PKC-epsilon-specific peptide agonists
      increased Na,K-ATPase protein abundance in the BLM. Accordingly, dopamine
      increased Na,K-ATPase activity in alveolar epithelial cells through the
      exocytosis of Na,K-pumps from late endosomes into the basolateral membrane in a
      mechanism-dependent activation of the novel protein kinase C isozymes PKC-delta
      and PKC-epsilon.

PMID- 11950948
TI  - Inhibition of anchorage-independent growth of transformed NIH3T3 cells by
      epithelial protein lost in neoplasm (EPLIN) requires localization of EPLIN to
      actin cytoskeleton.
AB  - Epithelial protein lost in neoplasm (EPLIN) is a cytoskeleton-associated protein
      characterized by the presence of a single centrally located lin-11, isl-1, and
      mec-3 (LIM) domain. We have reported previously that EPLIN is down-regulated in
      transformed cells. In this study, we have investigated whether ectopic expression
      of EPLIN affects transformation. In untransformed NIH3T3 cells, retroviral
      mediated transduction of EPLIN did not alter the cell morphology or growth.
      NIH3T3 cells expressing EPLIN, however, failed to form colonies when transformed
      by the activated Cdc42 or the chimeric nuclear oncogene EWS/Fli-1. This
      suppression of anchorage-independent growth was not universal because EPLIN
      failed to inhibit the colony formation of Ras-transformed cells. Interestingly,
      the localization of EPLIN to the actin cytoskeleton was maintained in the EWS/Fli
      1- or Cdc42-transformed cells, but not in Ras-transformed cells where it was
      distributed heterogeneously in the cytoplasm. Using truncated EPLIN constructs,
      we demonstrated that the NH(2)-terminal region of EPLIN is necessary for both the
      localization of EPLIN to the actin cytoskeleton and suppression of anchorage
      independent growth of EWS/Fli-1-transformed cells. The LIM domain or the COOH
      terminal region of EPLIN could be deleted without affecting its cytoskeletal
      localization or ability to suppress anchorage-dependent growth. Our study
      indicates EPLIN may function in growth control by associating with and regulating
      the actin cytoskeleton.

PMID- 11950947
TI  - Morphology and dynamics of the endocytic pathway in Dictyostelium discoideum.
AB  - Dictyostelium discoideum is a genetically and biochemically tractable social
      amoeba belonging to the crown group of eukaryotes. It performs some of the tasks
      characteristic of a leukocyte such as chemotactic motility, macropinocytosis, and
      phagocytosis that are not performed by other model organisms or are difficult to
      study. D. discoideum is becoming a popular system to study molecular mechanisms
      of endocytosis, but the morphological characterization of the organelles along
      this pathway and the comparison with equivalent and/or different organelles in
      animal cells and yeasts were lagging. Herein, we used a combination of evanescent
      wave microscopy and electron microscopy of rapidly frozen samples to visualize
      primary endocytic vesicles, vesicular-tubular structures of the early and late
      endo-lysosomal system, such as multivesicular bodies, and the specialized
      secretory lysosomes. In addition, we present biochemical and morphological
      evidence for the existence of a micropinocytic pathway, which contributes to the
      uptake of membrane along side macropinocytosis, which is the major fluid phase
      uptake process. This complex endosomal compartment underwent continuous cycles of
      tubulation/vesiculation as well as homo- and heterotypic fusions, in a way
      reminiscent of mechanisms and structures documented in leukocytes. Finally,
      egestion of fluid phase from the secretory lysosomes was directly observed.

PMID- 11950949
TI  - Kinesin-II is required for flagellar sensory transduction during fertilization in
      Chlamydomonas.
AB  - The assembly and maintenance of eucaryotic flagella and cilia depend on the
      microtubule motor, kinesin-II. This plus end-directed motor carries
      intraflagellar transport particles from the base to the tip of the organelle,
      where structural components of the axoneme are assembled. Here we test the idea
      that kinesin-II also is essential for signal transduction. When mating-type plus
      (mt+) and mating-type minus (mt-) gametes of the unicellular green alga
      Chlamydomonas are mixed together, binding interactions between mt+ and mt-
      flagellar adhesion molecules, the agglutinins, initiate a signaling pathway that
      leads to increases in intracellular cAMP, gamete activation, and zygote
      formation. A critical question in Chlamydomonas fertilization has been how
      agglutinin interactions are coupled to increases in intracellular cAMP. Recently,
      fla10 gametes with a temperature-sensitive defect in FLA10 kinesin-II were found
      to not form zygotes at the restrictive temperature (32 degrees C). We found that,
      although the rates and extents of flagellar adhesion in fla10 gametes at 32
      degrees C are indistinguishable from wild-type gametes, the cells do not undergo
      gamete activation. On the other hand, fla10 gametes at 32 degrees C regulated
      agglutinin location and underwent gamete fusion when the cells were incubated in
      dibutyryl cAMP, indicating that their capacity to respond to the cAMP signal was
      intact. We show that the cellular defect in the fla10 gametes at 32 degrees C is
      a failure to undergo increases in cAMP during flagella adhesion. Thus, in
      addition to being essential for assembly and maintenance of the structural
      components of flagella, kinesin-II/intraflagellar transport plays a role in
      sensory transduction in these organelles.

PMID- 11950950
TI  - Mutations in Saccharomyces cerevisiae gene SIR2 can have differential effects on
      in vivo silencing phenotypes and in vitro histone deacetylation activity.
AB  - The yeast SIR2 gene and many of its homologs have been identified as NAD(+)
      dependent histone deacetylases. To get a broader view of the relationship between
      the histone deacetylase activity of Sir2p and its in vivo functions we have
      mutated eight highly conserved residues in the core domain of SIR2. These
      mutations have a range of effects on the ability of Sir2p to deacetylate histones
      in vitro and to silence genes at the telomeres and HM loci. Interestingly, there
      is not a direct correlation between the in vitro and in vivo effects in some of
      these mutations. We also show that the histone deacetylase activity of Sir2p is
      necessary for the proper localiztion of the SIR complex to the telomeres.

PMID- 11950951
TI  - Acid phosphatases.
AB  - Acid phosphatases (APs) are a family of enzymes that are widespread in nature,
      and can be found in many animal and plant species. Mystery surrounds the precise
      functional role of these molecular facilitators, despite much research. Yet,
      paradoxically, human APs have had considerable impact as tools of clinical
      investigation and intervention. One particular example is tartrate resistant acid
      phosphatase, which is detected in the serum in raised amounts accompanying
      pathological bone resorption. This article seeks to explore the identity and
      diversity of APs, and to demonstrate the relation between APs, human disease, and
      clinical diagnosis.

PMID- 11950952
TI  - Methods of molecular analysis: mutation detection in solid tumours.
AB  - Most mutation detection techniques are unsuitable for routine use on solid
      tumours. Important parameters include sensitivity, specificity, efficiency, use
      of existing resources, and cost. In the UK, < 0.2% of service genetics laboratory
      activity involves mutation analysis in tumours (usually for family studies),
      mainly because it is time consuming/labour intensive (thus expensive) and DNA
      extracted from formalin fixed, paraffin wax embedded tissue is of low quality and
      yield. The small size of DNA fragments obtained from tissue blocks limits the
      polymerase chain reaction, the basis of most mutation detection methods. Other,
      biological, factors include: (1) heterogeneity of mutations within and between
      tumours, (2) variation in type and site of mutations in any one gene, (3) normal
      tissue harbouring mutations, (4) few genes are mutated in most of any one tumour
      type, and (5) few clinically useful correlations with genetic changes have been
      found. Present research is centred on correlating single gene mutations with
      various clinicopathological features, but the pattern of mutations in a
      combination of genes will probably prove more useful. Microsatellite instability,
      however, appears to be worth testing for in both familial and sporadic tumours,
      particularly of the colorectum.

PMID- 11950953
TI  - Molecular histology in the study of solid tumours.
AB  - Dominant oncogenes and tumour suppressor gene abnormalities are crucial events in
      human cancer. Many molecular techniques are used to identify these abnormalities,
      including single strand conformational polymorphism, the polymerase chain
      reaction, cloning, and sequencing, although the biological relevance of these
      changes is not always apparent. Immuno-histochemistry (ICH) or western blotting
      of abnormal gene products can provide information about their cellular
      localisation and expression in neoplastic versus normal cells, and can sometimes
      give a clue to their function. For example, ICH has shown how loss of the
      intercellular adhesion molecule E-cadherin, or abnormal localisation from the
      cell membrane to the cytoplasm, correlates with a diffuse tumour phenotype and a
      less favourable clinical outcome. Similarly, ICH of beta-catenin (a protein that
      binds E-cadherin and is essential for its function) has shown abnormal cellular
      localisation in the nucleus in a variety of human malignancies; in particular,
      colorectal carcinomas, where abnormal forms of the adenomatous polyposis coli
      gene product cause nuclear and cytoplasmic sequestration of beta-catenin. Such
      studies show how morphological assessment can sometimes provide insight into
      molecular function and dysfunction in human malignancy.

PMID- 11950954
TI  - New evidence for a viral pathogenic mechanism for new variant inflammatory bowel
      disease and development disorder?

PMID- 11950955
TI  - Potential viral pathogenic mechanism for new variant inflammatory bowel disease.
AB  - AIMS: A new form of inflammatory bowel disease (ileocolonic lymphonodular
      hyperplasia) has been described in a cohort of children with developmental
      disorder. This study investigates the presence of persistent measles virus in the
      intestinal tissue of these patients (new variant inflammatory bowel disease) and
      a series of controls by molecular analysis. METHODS: Formalin fixed, paraffin wax
      embedded and fresh frozen biopsies from the terminal ileum were examined from
      affected children and histological normal controls. The measles virus Fusion (F)
      and Haemagglutinin (H) genes were detected by TaqMan reverse transcription
      polymerase chain reaction (RT-PCR) and the Nucleocapsid (N) gene by RT in situ
      PCR. Localisation of the mRNA signal was performed using a specific follicular
      dendritic cell antibody. RESULTS: Seventy five of 91 patients with a
      histologically confirmed diagnosis of ileal lymphonodular hyperplasia and
      enterocolitis were positive for measles virus in their intestinal tissue compared
      with five of 70 control patients. Measles virus was identified within the
      follicular dendritic cells and some lymphocytes in foci of reactive follicular
      hyperplasia. The copy number of measles virus ranged from one to 300,00 copies/ng
      total RNA. CONCLUSIONS: The data confirm an association between the presence of
      measles virus and gut pathology in children with developmental disorder.

PMID- 11950957
TI  - Expression of chondrocyte markers by cells of normal and degenerate
      intervertebral discs.
AB  - AIMS: To investigate the phenotype of cells in normal and degenerate
      intervertebral discs by studying the expression of molecules characteristic of
      chondrocytes in situ. METHODS: Human intervertebral discs taken at surgery were
      graded histologically, and classified on this basis as normal or degenerate.
      Eighteen of each type were selected, and in situ hybridisation was performed for
      the chondrocytic markers Sox9 and collagen II using (35)S labelled cDNA probes.
      Aggrecan was located by immunohistochemistry, using the monoclonal antibody
      HAG7E1, and visualised with an avidin-biotin peroxidase system. RESULTS: In the
      normal discs, strong signals for Sox9 and collagen II mRNA, and strong staining
      for the aggrecan protein were seen for the cells of the nucleus pulposus (NP),
      but reactions were weak or absent over the cells of the annulus fibrosus (AF). In
      degenerate discs, the Sox9 and collagen II mRNA signals remained visible over the
      cells of the NP and were again absent in the AF. Aggrecan staining was not
      visible in the NP cells, and was again absent in the AF. CONCLUSIONS: Cells of
      the normal NP showed expression of all three markers, clearly indicating a
      chondrocytic phenotype. In degeneration, there was evidence of a loss of aggrecan
      synthesis, which may contribute to the pathogenesis of disc degeneration. AF
      cells showed no evidence of a chondrocytic phenotype in either normal or
      degenerate discs.

PMID- 11950958
TI  - Improvements to B cell clonality analysis using PCR amplification of
      immunoglobulin light chain genes.
AB  - AIMS: Clonality analysis using polymerase chain reaction (PCR) amplification of
      the immunoglobulin heavy chain (IgH) gene is an important aid to the diagnosis of
      B cell lymphoproliferative diseases. However, the method has a relatively high
      false negative rate. In an attempt to improve detection rates simple PCR
      strategies for clonality analysis of B cell populations using amplification of Ig
      light chain genes have been developed. METHODS: Novel PCR protocols, designed to
      amplify Ig kappa and Ig lambda light chain genes, were evaluated using high
      molecular weight DNA samples from 28 selected cases of B cell lymphoma with known
      light chain expression and 12 reactive lymphoid specimens. Products were run on
      10% polyacrylamide minigels using heteroduplex analysis. Conventional IgH PCR
      analysis was also performed. Twelve randomly selected formalin fixed, paraffin
      wax processed samples from cases submitted for molecular genetic analysis were
      also studied. RESULTS: Polyclonal products were seen in all reactive lymphoid
      samples. Using Ig kappa PCR, 24 of 28 lymphomas, including four of five IgH
      negative cases, displayed monoclonal patterns. Using Ig lambda PCR, eight of 12
      Ig lambda expressing tumours, including two of five IgH negative cases, showed
      monoclonal patterns. Standard IgH PCR demonstrated monoclonality in 23 of 28 B
      cell lymphomas. The detection rate was improved to 27 of 28 lymphomas using heavy
      and light chain PCR. Efficient amplification was achieved using paraffin wax
      processed samples, seven of which showed monoclonality compared with eight using
      IgH PCR. CONCLUSIONS: Ig light chain PCR, used in conjunction with heavy chain
      analysis, enables improved detection of B cell monoclonality using routine
      histological specimens and can provide additional clone specific markers for the
      study of the biology of B cell tumours.

PMID- 11950959
TI  - Treatment of murine breast cancer cells with antisense RNA to the type I insulin
      like growth factor receptor decreases the level of plasminogen activator
      transcripts, inhibits cell growth in vitro, and reduces tumorigenesis in vivo.
AB  - AIMS: To establish that cells from the murine mammary carcinoma cell line, EMT6,
      express type I insulin-like growth factor receptor (IGF-IR), tissue-type
      plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA). To
      investigate the role of IGF-IR in growth, transformation, and tumorigenesis in
      addition to its relation to tPA and uPA in EMT6 cells. To assess the suitability
      of the EMT6/syngeneic mouse model for studying the role of IGF-IR in
      tumorigenesis. METHODS: The presence of transcripts for IGF-IR, tPA, and uPA was
      determined by northern blot analysis using poly (A(+)) RNA derived from EMT6
      cells transfected with an antisense IGF-IR construct or a construct lacking the
      antisense IGF-IR insert. Flow cytometry was used to measure IGF-IR protein.
      Assays were performed to determine cell proliferation, transformation, and the
      tumorigenicity of antisense IGF-IR transfected EMT6 cells and control transfected
      EMT6 cells. RESULTS: There was strong expression of IGF-IR, tPA, and uPA in EMT6
      cells. EMT6 cells from clones carrying antisense IGF-IR displayed a significant
      decrease in cell proliferation and lost the ability to form colonies in soft
      agar. A decrease in tumour size occurred when cells carrying the antisense IGF-IR
      were injected into syngeneic mice. Reduced expression of tPA and uPA was seen in
      EMT6 cells carrying the antisense IGF-IR construct. CONCLUSIONS: The IGF-IR plays
      a role in the progression, transformation, and tumorigenesis of EMT6 murine
      mammary carcinoma cells. The suppression of IGF-IR mRNA in EMT6 cells decreases
      tPA and uPA expression. EMT6 cells and the syngeneic mouse provide a suitable
      model for studying the role of IGF-IR in breast tumour progression.

PMID- 11950960
TI  - CD40 activation in epithelial ovarian carcinoma cells modulates growth,
      apoptosis, and cytokine secretion.
AB  - BACKGROUND/AIMS: CD40, a member of the tumour necrosis factor (TNF) receptor
      family, is expressed on a variety of haematopoietic cells and is crucial in
      orchestrating both humoral and cellular immune responses. CD40 is also expressed
      on some carcinoma cells, where its function remains largely unknown. This study
      investigated the effects of CD40 ligation on ovarian carcinoma cell growth and
      apoptosis and on cytokine production, in addition to the role of the NF-kappa B
      and JNK signalling pathways. METHODS: CD40 expression was measured in epithelial
      ovarian carcinoma (EOC) biopsies by immunohistochemistry and in EOC cell lines by
      flow cytometry. To examine the effects of CD40 ligation on cell growth
      recombinant soluble CD40 ligand was used to stimulate EOC cell lines and growth
      was measured by MMT assays. Cytokine production was measured by enzyme linked
      immunosorbent assays interleukin 8 (IL-8) gene transcription was estimated by
      means of reverse transcription polymerase chain reaction. The integrity of the
      CD40 signalling pathway in those cell lines that did not produce cytokines in
      response to CD40 ligation was assessed by the detection of the transcription
      factor NF-kappa B by an electrophoretic mobility shift assay. To investigate the
      defect in the NF-kappa B pathway the phosphorylation status of I kappa B alpha
      was determined by an antibody specific to phosphorylated I kappa B alpha and
      dissociation of the I kappa B alpha-p65 complex was assessed by co
      immunoprecipitation. RESULTS: CD40 is expressed in primary ovarian carcinoma
      biopsies and EOC cell lines. CD40 ligation resulted in growth inhibition in most
      of these carcinoma cell lines and was also found to promote apoptosis, with this
      last effect only being evident in early passage EOC cells. CD40 ligation also
      induced significant IL-6 and IL-8 production in most of the EOC cell lines
      examined and it was confirmed for IL-8 that this effect was regulated at the
      transcriptional level. NF-kappa B activation in response to CD40 ligation was
      found in three of the EOC cell lines and specific defects in the CD40 induced NF
      kappa B pathway were identified in two cell lines. However, CD40 engagement
      induced JNK activation in all the EOC cell lines. CONCLUSIONS: These data suggest
      that the CD40 pathway is functional in ovarian carcinoma cells and highlight the
      need for further studies to provide insight into the role of CD40 in the
      carcinogenic process and the possible exploitation of this pathway for novel
      therapeutic approaches.

PMID- 11950961
TI  - Improved technique for fluorescence in situ hybridisation analysis of isolated
      nuclei from archival, B5 or formalin fixed, paraffin wax embedded tissue.
AB  - Fluorescence in situ hybridisation (FISH) is an effective method to detect
      chromosomal alterations in a variety of tissue types, including archived paraffin
      wax embedded specimens fixed in B5 or formalin. However, precipitating fixatives
      such as B5 have been known to produce unsatisfactory results in comparison with
      formalin when used for FISH. This study describes an effective nuclear isolation
      and FISH procedure for B5 and formalin fixed tissue, optimising the nuclear
      isolation step and nuclei pretreatments using tonsil and mantle cell lymphoma
      specimens. The protocol presented can be used to isolate nuclei and perform FISH
      on B5 or formalin fixed, paraffin wax embedded samples from a variety of tissue
      types.

PMID- 11950965
TI  - Calmodulin as a potential negative regulator of Arabidopsis COR gene expression.

PMID- 11950966
TI  - Enantiomeric-dependent phytotoxic and antimicrobial activity of (+/-)-catechin. A
      rhizosecreted racemic mixture from spotted knapweed.

PMID- 11950963
TI  - Haemophilia A and haemophilia B: molecular insights.
AB  - This review focuses on selected areas that should interest both the scientist and
      the clinician alike: polymorphisms within the factor VIII and factor IX genes,
      their linkage, and their ethnic variation; a general assessment of mutations
      within both genes and a detailed inspection of the molecular pathology of certain
      mutations to illustrate the diverse cause-effect relations that exist; a summary
      of current knowledge on molecular aspects of inhibitor production; and an
      introduction to the new areas of factor VIII and factor IX catabolism. An
      appendix defining various terms encountered in the molecular genetics of the
      haemophilias is included, together with an appendix providing accession numbers
      and locus identification links for accessing gene and sequence information in the
      international nucleic acid databases.

PMID- 11950967
TI  - Guard cell- and phloem idioblast-specific expression of thioglucoside
      glucohydrolase 1 (myrosinase) in Arabidopsis.
AB  - Thioglucoside glucohydrolase 1 (TGG1) is one of two known functional myrosinase
      enzymes in Arabidopsis. The enzyme catalyzes the hydrolysis of glucosinolates
      into compounds that are toxic to various microbes and herbivores. Transgenic
      Arabidopsis plants carrying beta-glucuronidase and green fluorescent protein
      reporter genes fused to 0.5 or 2.5 kb of the TGG1 promoter region were used to
      study spatial promoter activity. Promoter activity was found to be highly
      specific and restricted to guard cells and distinct cells of the phloem. No
      promoter activity was detected in the root or seed. All guard cells show promoter
      activity. Positive phloem cells are distributed in a discontinuous pattern and
      occur more frequent in young tissues. Immunocytochemical localization of
      myrosinase in transverse and longitudinal sections of embedded material show that
      the TGG1 promoter activity reflects the position of the myrosinase enzyme. In the
      flower stalk, the myrosinase-containing phloem cells are located between phloem
      sieve elements and glucosinolate-rich S cells. Our results suggest a cellular
      separation of myrosinase enzyme and glucosinolate substrate, and that myrosinase
      is contained in distinct cells. We discuss the potential advantages of locating
      defense and communication systems to only a few specific cell types.

PMID- 11950968
TI  - Functional interactions between heterologously expressed starch-branching enzymes
      of maize and the glycogen synthases of Brewer's yeast.
AB  - Starch-branching enzymes (SBEs) catalyze the formation of alpha(1-->6) glycoside
      bonds in glucan polymers, thus, affecting the structure of amylopectin and starch
      granules. Two distinct classes of SBE are generally conserved in higher plants,
      although the specific role(s) of each isoform in determination of starch
      structure is not clearly understood. This study used a heterologous in vivo
      system to isolate the function of each of the three known SBE isoforms of maize
      (Zea mays) away from the other plant enzymes involved in starch biosynthesis. The
      ascomycete Brewer's yeast (Saccharomyces cerevisiae) was employed as the host
      species. All possible combinations of maize SBEs were expressed in the absence of
      the endogenous glucan-branching enzyme. Each maize SBE was functional in yeast
      cells, although SBEI had a significant effect only if SBEIIa and SBEIIb also were
      present. SBEI by itself did not support glucan accumulation, whereas SBEIIa and
      SBEIIb both functioned along with the native glycogen synthases (GSs) to produce
      significant quantities of alpha-glucan polymers. SBEIIa was phenotypically
      dominant to SBEIIb in terms of glucan structure. The specific branching enzyme
      present had a significant effect on the molecular weight of the product. From
      these data we suggest that SBEs and GSs work in a cyclically interdependent
      fashion, such that SBE action is needed for optimal GS activity; and GS, in turn,
      influences the further effects of SBE. Also, SBEIIa and SBEIIb appear to act
      before SBEI during polymer assembly in this heterologous system.

PMID- 11950969
TI  - Steroleosin, a sterol-binding dehydrogenase in seed oil bodies.
AB  - Besides abundant oleosin, three minor proteins, Sop 1, 2, and 3, are present in
      sesame (Sesamum indicum) oil bodies. The gene encoding Sop1, named caleosin for
      its calcium-binding capacity, has recently been cloned. In this study, Sop2 gene
      was obtained by immunoscreening, and it was subsequently confirmed by amino acid
      partial sequencing and immunological recognition of its overexpressed protein in
      Escherichia coli. Immunological cross recognition implies that Sop2 exists in
      seed oil bodies of diverse species. Along with oleosin and caleosin genes, Sop2
      gene was transcribed in maturing seeds where oil bodies are actively assembled.
      Sequence analysis reveals that Sop2, tentatively named steroleosin, possesses a
      hydrophobic anchoring segment preceding a soluble domain homologous to sterol
      binding dehydrogenases/reductases involved in signal transduction in diverse
      organisms. Three-dimensional structure of the soluble domain was predicted via
      homology modeling. The structure forms a seven-stranded parallel beta-sheet with
      the active site, S-(12X)-Y-(3X)-K, between an NADPH and a sterol-binding
      subdomain. Sterol-coupling dehydrogenase activity was demonstrated in the
      overexpressed soluble domain of steroleosin as well as in purified oil bodies.
      Southern hybridization suggests that one steroleosin gene and certain homologous
      genes may be present in the sesame genome. Comparably, eight hypothetical
      steroleosin-like proteins are present in the Arabidopsis genome with a conserved
      NADPH-binding subdomain, but a divergent sterol-binding subdomain. It is
      indicated that steroleosin-like proteins may represent a class of
      dehydrogenases/reductases that are involved in plant signal transduction
      regulated by various sterols.

PMID- 11950970
TI  - The rice mutant esp2 greatly accumulates the glutelin precursor and deletes the
      protein disulfide isomerase.
AB  - Rice (Oryza sativa) accumulates prolamins and glutelins as storage proteins. The
      latter storage protein is synthesized on the endoplasmic reticulum (ER) as a 57
      kD proglutelin precursor, which is then processed into acidic and basic subunits
      in the protein storage vacuole. Three esp2 mutants, CM1787, EM44, and EM747,
      contain larger amounts of the 57-kD polypeptide and corresponding lower levels of
      acidic and basic glutelin subunits than normal. Electron microscopic observation
      revealed that esp2 contained normal-appearing glutelin-containing protein bodies
      (PB-II), but lacked the normal prolamin-containing PB (PB-I). Instead, numerous
      small ER-derived PBs of uniform size (0.5 microm in diameter) and low electron
      density were readily observed. Immunoblot analysis of purified subcellular
      fractions and immunocytochemistry at the electron microscopy level showed that
      these new PBs contained the 57-kD proglutelin precursor and prolamin
      polypeptides. The 57-kD proglutelin was extracted with 1% (v/v) lactic acid
      solution only after removal of cysteine-rich prolamin polypeptides, suggesting
      that these proteins form glutelin-prolamin aggregates via interchain disulfide
      bonds within the ER lumen. The endosperm of esp2 mutants contains the lumenal
      chaperones, binding protein and calnexin, but lacks protein disulfide isomerase
      (PDI) at the protein and RNA levels. The transcript of PDI was expressed in the
      seed only during the early stage of seed development in the wild type. These
      results suggest that PDI plays an essential role in the segregation of
      proglutelin and prolamin polypeptides within the ER lumen.

PMID- 11950972
TI  - Preexisting systemic acquired resistance suppresses hypersensitive response
      associated cell death in Arabidopsis hrl1 mutant.
AB  - The hypersensitive response (HR) displayed by resistant plants against invading
      pathogens is a prominent feature of plant-pathogen interactions. The Arabidopsis
      hypersensitive response like lesions1 (hrl1) mutant is characterized by
      heightened defense responses that make it more resistant to virulent pathogens.
      However, hrl1 suppresses avirulent pathogen-induced HR cell death. Furthermore,
      the high PR-1 expression observed in hrl1 remains unaltered after avirulent and
      virulent pathogen infections. The suppressed HR phenotype in hrl1 is observed
      even when an elicitor is expressed endogenously from an inducible promoter,
      suggesting that an impaired transfer of avirulent factors is not the reason.
      Interestingly, the lack of HR phenotype in hrl1 is reversed if the constitutive
      defense responses are compromised either by a mutation in NON EXPRESSOR OF PR-1
      (NPR1) or by depleting salicylic acid due to the expression of the nahG gene. The
      rescue of HR cell death in hrl1 npr1 and in hrl1 nahG depends on the extent to
      which the constitutive systemic acquired response (SAR) is compromised.
      Pretreating Arabidopsis wild-type plants with SAR-inducers, before pathogen
      infection resulted in a significant decrease in HR cell death. Together, these
      results demonstrate that the preexisting SAR may serve as one form of negative
      feedback loop to regulate HR-associated cell death in hrl1 mutant and in the wild
      type plants.

PMID- 11950971
TI  - Functional properties and regulatory complexity of a minimal RBCS light
      responsive unit activated by phytochrome, cryptochrome, and plastid signals.
AB  - Light-inducible promoters are able to respond to a wide spectrum of light through
      multiple photoreceptor systems. Several cis-acting elements have been identified
      as components of light-responsive promoter elements; however, none of these
      regulatory elements by itself appears to be sufficient to confer light
      responsiveness; rather, the combination of at least two elements seems to be
      required. Using phylogenetic structural analysis, we have identified conserved
      DNA modular arrays (CMAs) associated with light-responsive promoter regions that
      have been conserved throughout the evolutionary radiation of angiosperms. Here,
      we report the functional characterization of CMA5, a native 52-bp fragment of the
      Nicotiana plumbaginifolia rbcS 8B promoter, which contains an I- and a G-box cis
      element. CMA5 behaves as a light-responsive minimal unit capable of activating a
      heterologous minimal promoter in a phytochrome-, cryptochrome-, and plastid
      dependent manner. We also show that CMA5 light induction requires HY5 and that
      downstream negative regulators COP (constitutive photomorphogenic)/DET (de
      etiolated) regulate its activity. Our results show that the simplest light
      responsive promoter element from photosynthesis-associated genes described to
      date is the common target for different signals involved in light regulation. The
      possible mechanism involved in light-transcriptional regulation and tissue
      specificity of combinatorial elements units is discussed.

PMID- 11950973
TI  - Characterization of CAX4, an Arabidopsis H(+)/cation antiporter.
AB  - Ion compartmentalization is essential for plant growth and development. The
      Arabidopsis open reading frames for CAX1, CAX2, and CAX3 (cation exchangers 1, 2,
      and 3) were previously identified as transporters that may modulate ion fluxes
      across the vacuolar membrane. To understand the diversity and role of H(+)/cation
      transporters in controlling plant ion levels, another homolog of the CAX genes,
      CAX4, was cloned from an Arabidopsis cDNA library. CAX4 is 53% identical to CAX1
      at the amino acid level, 42% identical to CAX2, and 54% identical to CAX3. CAX4
      transcripts appeared to be expressed at low levels in all tissues and levels of
      CAX4 RNA increased after Mn(2+), Na(+), and Ni(2+) treatment. An N-terminal CAX4
      hemagglutinin fusion appeared to localize to both yeast and plant vacuolar
      membranes. When expressed in yeast, CAX4, like CAX3, failed to suppress the
      Ca(2+) sensitivity of yeast strains deficient in vacuolar Ca(2+) transport.
      Several modifications to CAX4 allowed the protein to transport Ca(2+). Addition
      of amino acids to the N terminus of CAX4 and CAX3 caused both transporters to
      suppress the sensitivity of yeast strains deficient in vacuolar Ca(2+) transport.
      These findings suggest that CAX transporters may modulate their ion transport
      properties through alterations at the N terminus.

PMID- 11950974
TI  - Altering the expression of the chlorophyllase gene ATHCOR1 in transgenic
      Arabidopsis caused changes in the chlorophyll-to-chlorophyllide ratio.
AB  - The Arabidopsis gene ATHCOR1, which encodes the CORI1 (coronatine-induced)
      protein, was expressed in bacterial cells. Soluble recombinant CORI1 was purified
      and shown to possess chlorophyllase (Chlase) activity in vitro. To determine its
      activity in vivo, wild-type Arabidopsis and coi1 mutant, which lacks ATHCOR1
      transcripts, were transformed with sense and antisense forms of the gene. Wild
      type and coi1 plants overexpressing ATHCOR1 showed increased contents of
      chlorophyllide (Chlide) without a substantial change in the total amount of the
      extractable chlorophyll (Chl). These plants presented high Chlide to Chl ratios
      in leaves, whereas antisense plants and nontransformed coi1 mutant showed
      undetectable ATHCOR1 mRNA and significantly lower Chlide to Chl ratios, relative
      to wild-type control. Overexpression of ATHCOR1 caused an increased breakdown of
      Chl a, as revealed by the Chlide a to b ratio, which was significantly higher in
      sense than wild-type, coi1 mutant, and antisense plants. This preferential
      activity of CORI1 toward Chl a was further supported by in vitro analyses using
      the purified protein. Increased Chlase activity was detected in developing
      flowers, which correlated to the constitutive expression of ATHCOR1 in this
      organ. Flowers of the antisense plant showed reduced Chlide to Chl ratio,
      suggesting a role of CORI1 in Chl breakdown during flower senescence. The results
      show that ATHCOR1 has Chlase activity in vivo, however, because coi1 flowers have
      no detectable ATHCOR1 mRNA and present Chlide to Chl ratios comparable with the
      wild type, an additional Chlase is likely to be active in Arabidopsis. In
      accordance, transcripts of a second Arabidopsis Chlase gene, AtCLH2, were
      detected in both normal and mutant flowers.

PMID- 11950975
TI  - The alpha-amylase induction in endosperm during rice seed germination is caused
      by gibberellin synthesized in epithelium.
AB  - We recently isolated two genes (OsGA3ox1 and OsGA3ox2) from rice (Oryza sativa)
      encoding 3beta-hydroxylase, which catalyzes the final step of active gibberellin
      (GA) biosynthesis (H. Itoh, M. Ueguchi-Tanaka, N. Sentoku, H. Kitano, M.
      Matsuoka, M. Kobayashi [2001] Proc Natl Acad Sci USA 98: 8909-8914). Using these
      cloned cDNAs, we analyzed the temporal and spatial expression patterns of the
      3beta-hydroxylase genes and also an alpha-amylase gene (RAmy1A) during rice seed
      germination to investigate the relationship between GA biosynthesis and alpha
      amylase expression. Northern-blot analyses revealed that RAmy1A expression in the
      embryo occurs before the induction of 3beta-hydroxylase expression, whereas in
      the endosperm, a high level of RAmy1A expression occurs 1 to 2 d after the peak
      of OsGA3ox2 expression and only in the absence of uniconazol. Based on the
      analysis of an OsGA3ox2 null mutant (d18-Akibare dwarf), we determined that 3beta
      hydroxylase produced by OsGA3ox2 is important for the induction of RAmy1A
      expression and that the OsGA3ox1 product is not essential for alpha-amylase
      induction. The expression of OsGA3ox2 was localized to the shoot region and
      epithelium of the embryo, strongly suggesting that active GA biosynthesis occurs
      in these two regions. The synthesis of active GA in the epithelium is important
      for alpha-amylase expression in the endosperm, because an embryonic mutant
      defective in shoot formation, but which developed epithelium cells, induced alpha
      amylase expression in the endosperm, whereas a mutant defective in epithelium
      development did not.

PMID- 11950976
TI  - Oxidative stress increased respiration and generation of reactive oxygen species,
      resulting in ATP depletion, opening of mitochondrial permeability transition, and
      programmed cell death.
AB  - Mitochondria constitute a major source of reactive oxygen species and have been
      proposed to integrate the cellular responses to stress. In animals, it was shown
      that mitochondria can trigger apoptosis from diverse stimuli through the opening
      of MTP, which allows the release of the apoptosis-inducing factor and
      translocation of cytochrome c into the cytosol. Here, we analyzed the role of the
      mitochondria in the generation of oxidative burst and induction of programmed
      cell death in response to brief or continuous oxidative stress in Arabidopsis
      cells. Oxidative stress increased mitochondrial electron transport, resulting in
      amplification of H(2)O(2) production, depletion of ATP, and cell death. The
      increased generation of H(2)O(2) also caused the opening of the MTP and the
      release of cytochrome c from mitochondria. The release of cytochrome c and cell
      death were prevented by a serine/cysteine protease inhibitor, Pefablock. However,
      addition of inhibitor only partially inhibited the H(2)O(2) amplification and the
      MTP opening, suggesting that protease activation is a necessary step in the cell
      death pathway after mitochondrial damage.

PMID- 11950977
TI  - Constitutive expression of the beta-ketothiolase gene in transgenic plants. A
      major obstacle for obtaining polyhydroxybutyrate-producing plants.
AB  - Polyhydroxybutyrate (PHB) is a member of a class of thermoelastic polymers called
      polyhydroxyalkanoates that serve many bacteria as intracellular storage molecules
      for carbon and energy. Transgenic plants provide a potential means of producing
      this polymer cost-effectively. To date, however, few reports of the successful
      production of this polymer have been published, with the exception of work with
      transgenic Arabidopsis. Using a variety of chimeric constructs, we have
      determined that the constitutive, chloroplast-localized expression of one of the
      genes involved in PHB production-the beta-ketothiolase (phbA) gene-is detrimental
      to the efficient production of transgenic PHB. The alternate use of either
      inducible or somatically activated promoters allowed the construction of
      transgenic PHB-producing potato (Solanum tuberosum) and tobacco (Nicotiana
      tabacum) plants, although the amount of PHB formed was still rather low. Taking
      advantage of an inducible promoter, the maximal amount of PHB produced in
      transgenic potato was 0.09 mg g(-1) dry weight. In transgenic tobacco using a
      somatically activated promoter, up to 3.2 mg g(-1) dry weight was accumulated. In
      Arabidopsis, the formation of high levels of PHB had previously been shown to be
      accompanied by severe negative effects on growth and development of the plant.
      Phasins are proteins known from PHB-producing bacteria speculated to serve as
      protectants against the highly hydrophobic surface of the PHB granules in the
      bacterial intracellular milieu. Co-expression of the phasin gene in parallel with
      the PHB synthesis genes, however, did not lead to reduced symptom development.

PMID- 11950978
TI  - Ocatin. A novel tuber storage protein from the andean tuber crop oca with
      antibacterial and antifungal activities.
AB  - The most abundant soluble tuber protein from the Andean crop oca (Oxalis tuberosa
      Mol.), named ocatin, has been purified and characterized. Ocatin accounts for 40%
      to 60% of the total soluble oca tuber proteins, has an apparent molecular mass of
      18 kD and an isoelectric point of 4.8. This protein appears to be found only in
      tubers and is accumulated only within the cells of the pith and peridermis layers
      (peel) of the tuber as it develops. Ocatin inhibits the growth of several
      phytopathogenic bacteria (Agrobacterium tumefaciens, Agrobacterium radiobacter,
      Serratia marcescens, and Pseudomonas aureofaciens) and fungi (Phytophthora
      cinnamomi, Fusarium oxysporum, Rhizoctonia solani, and Nectria hematococcus).
      Ocatin displays substantial amino acid sequence similarity with a widely
      distributed group of intracellular pathogenesis-related proteins with a hitherto
      unknown biological function. Our results showed that ocatin serves as a storage
      protein, has antimicrobial properties, and belongs to the Betv 1/PR-10/MLP
      protein family. Our findings suggest that an ancient scaffolding protein was
      recruited in the oca tuber to serve a storage function and that proteins from the
      Betv 1/PR-10/MLP family might play a role in natural resistance to pathogens.

PMID- 11950979
TI  - Spermidine-binding proteins. Purification and expression analysis in maize.
AB  - Polyamine-binding proteins have been identified in a wide range of organisms,
      including mammals, yeasts, and bacteria. In this work, we have investigated
      specific spermidine binding to plant membrane proteins purified from microsomes
      of etiolated maize (Zea mays) coleoptiles. In the final purification step,
      specific spermidine-binding activity (K(d) 6.02 10(-7) M) was eluted from a
      HiTrapQ fast-protein liquid chromatography column at about 0.25 M NaCl, and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the most active
      fraction showed a major polypeptide of about 60 kD and another copurifying 18-kD
      protein. Competition experiments, performed on HiTrapQ active fractions,
      confirmed the specificity of the binding. Upon Sephadex G-100 gel filtration,
      spermidine binding was associated almost exclusively with the 18-kD protein. On
      the basis of the N-terminal sequences, degenerate oligonucleotide probes were
      designed and used to isolate, by reverse transcriptase-polymerase chain reaction
      and polymerase chain reaction, cDNA fragments of about 1 kb for the 60-kD
      protein, and 0.9 kb for the 18-kD protein. Northern-blot analysis performed on
      etiolated coleoptiles and different tissues from 10-d-old maize plants indicated
      the presence of two different mRNAs of 1.7 and 0.7 kb. Southern-blot analysis
      indicated that the genes encoding the 60- and 18-kD proteins are probably derived
      from differential processing of the same precursor mRNA. Using rabbit polyclonal
      antibodies raised against these proteins, affinity purification and dot-blot
      experiments detected analogous membrane proteins in monocot and dicot plants.

PMID- 11950981
TI  - Rate of dehydration and cumulative desiccation stress interacted to modulate
      desiccation tolerance of recalcitrant cocoa and ginkgo embryonic tissues.
AB  - Rate of dehydration greatly affects desiccation tolerance of recalcitrant seeds.
      This effect is presumably related to two different stress vectors: direct
      mechanical or physical stress because of the loss of water and physicochemical
      damage of tissues as a result of metabolic alterations during drying. The present
      study proposed a new theoretic approach to represent these two types of stresses
      and investigated how seed tissues responded differently to two stress vectors,
      using the models of isolated cocoa (Theobroma cacao) and ginkgo (Ginkgo biloba)
      embryonic tissues dehydrated under various drying conditions. This approach used
      the differential change in axis water potential (DeltaPsi/Deltat) to quantify
      rate of dehydration and the intensity of direct physical stress experienced by
      embryonic tissues during desiccation. Physicochemical effect of drying was
      expressed by cumulative desiccation stress [integralf(psi,t)], a function of both
      the rate and time of dehydration. Rapid dehydration increased the sensitivity of
      embryonic tissues to desiccation as indicated by high critical water contents,
      below which desiccation damage occurred. Cumulative desiccation stress increased
      sharply under slow drying conditions, which was also detrimental to embryonic
      tissues. This quantitative analysis of the stress-time-response relationship
      helps to understand the physiological basis for the existence of an optimal
      dehydration rate, with which maximum desiccation tolerance could be achieved. The
      established numerical analysis model will prove valuable for the design of
      experiments that aim to elucidate biochemical and physiological mechanisms of
      desiccation tolerance.

PMID- 11950980
TI  - Identification of Arabidopsis ethylene-responsive element binding factors with
      distinct induction kinetics after pathogen infection.
AB  - Ethylene-responsive element binding factors (ERF) proteins are plant-specific
      transcription factors, many of which have been linked to stress responses. We
      have identified four Arabidopsis ERF genes whose expression was specifically
      induced by avirulent and virulent strains of the bacterial pathogen Pseudomonas
      syringae pv tomato, with overlapping but distinct induction kinetics. However, a
      delay in ERF mRNA accumulation after infection with the virulent strain was
      observed when compared with the avirulent strain. The induction of ERF gene
      expression in most cases preceded the mRNA accumulation of a basic chitinase
      gene, a potential downstream target for one or more of these ERFs. The expression
      of the ERF genes was examined among different Arabidopsis tissues, in response to
      the signaling molecules ethylene, methyl jasmonate, and salicylic acid (SA), and
      in Arabidopsis mutants with decreased or enhanced susceptibility to pathogens,
      and significant differences were observed. For example, in seedlings, some of the
      ERF genes were not induced by SA in the wild-type but were SA responsive in the
      pad4-1 mutant, suggesting that PAD4-1, which acts upstream of SA accumulation, is
      also involved in repressing the SA-induced expression of specific ERF genes. The
      four ERF proteins were shown to contain transcriptional activation domains. These
      results suggest that transcriptional activation cascades involving ERF proteins
      may be important for plant defense to pathogen attack and that some ERF family
      members could be involved in the cross-talk between SA- and jasmonic acid
      signaling pathways.

PMID- 11950983
TI  - Transgenic expression in Arabidopsis of a polyprotein construct leading to
      production of two different antimicrobial proteins.
AB  - We developed a method for expression in Arabidopsis of a transgene encoding a
      cleavable chimeric polyprotein. The polyprotein precursor consists of a leader
      peptide and two different antimicrobial proteins (AMPs), DmAMP1 originating from
      Dahlia merckii seeds and RsAFP2 originating from Raphanus sativus seeds, which
      are linked by an intervening sequence ("linker peptide") originating from a
      natural polyprotein occurring in seed of Impatiens balsamina. The chimeric
      polyprotein was found to be cleaved in transgenic Arabidopsis plants and the
      individual AMPs were secreted into the extracellular space. Both AMPs were found
      to exert antifungal activity in vitro. It is surprising that the amount of AMPs
      produced in plants transformed with some of the polyprotein transgene constructs
      was significantly higher compared with the amount in plants transformed with a
      transgene encoding a single AMP, indicating that the polyprotein expression
      strategy may be a way to boost expression levels of small proteins.

PMID- 11950982
TI  - Sequence relationships, conserved domains, and expression patterns for maize
      homologs of the polycomb group genes E(z), esc, and E(Pc).
AB  - Polycomb group (PcG) proteins play an important role in developmental and
      epigenetic regulation of gene expression in fruit fly (Drosophila melanogaster)
      and mammals. Recent evidence has shown that Arabidopsis homologs of PcG proteins
      are also important for the regulation of plant development. The objective of this
      study was to characterize the PcG homologs in maize (Zea mays). The 11 cloned PcG
      proteins from fruit fly and the Enhancer of zeste [E(z)], extra sex combs (esc),
      and Enhancer of Polycomb [E(Pc)] homologs from Arabidopsis were used as queries
      to perform TBLASTN searches against the public maize expressed sequence tag
      database and the Pioneer Hi-Bred database. Maize homologs were found for E(z),
      esc, and E(Pc), but not for Polycomb, pleiohomeotic, Posterior sex combs,
      Polycomblike, Additional sex combs, Sex combs on midleg, polyhometoic, or multi
      sex combs. Transcripts of the three maize Enhancer of zeste-like genes, Mez1,
      Mez2, and Mez3, were detected in all tissues tested, and the Mez2 transcript is
      alternatively spliced in a tissue-dependent pattern. Zea mays fertilization
      independent endosperm1 (ZmFie1) expression was limited to developing embryos and
      endosperms, whereas ZmFie2 expression was found throughout plant development. The
      conservation of E(z) and esc homologs across kingdoms indicates that these genes
      likely play a conserved role in repressing gene expression.

PMID- 11950984
TI  - Influence of iron status on cadmium and zinc uptake by different ecotypes of the
      hyperaccumulator Thlaspi caerulescens.
AB  - We have previously identified an ecotype of the hyperaccumulator Thlaspi
      caerulescens (Ganges), which is far superior to other ecotypes (including Prayon)
      in Cd uptake. In this study, we investigated the effect of Fe status on the
      uptake of Cd and Zn in the Ganges and Prayon ecotypes, and the kinetics of Cd and
      Zn influx using radioisotopes. Furthermore, the T. caerulescens ZIP (Zn-regulated
      transporter/Fe-regulated transporter-like protein) genes TcZNT1-G and TcIRT1-G
      were cloned from the Ganges ecotype and their expression under Fe-sufficient and 
      deficient conditions was analyzed. Both short- and long-term studies revealed
      that Cd uptake was significantly enhanced by Fe deficiency only in the Ganges
      ecotype. The concentration-dependent kinetics of Cd influx showed that the V(max)
      of Cd was 3 times greater in Fe-deficient Ganges plants compared with Fe
      sufficient plants. In Prayon, Fe deficiency did not induce a significant increase
      in V(max) for Cd. Zn uptake was not influenced by the Fe status of the plants in
      either of the ecotypes. These results are in agreement with the gene expression
      study. The abundance of ZNT1-G mRNA was similar between the Fe treatments and
      between the two ecotypes. In contrast, abundance of the TcIRT1-G mRNA was greatly
      increased only in Ganges root tissue under Fe-deficient conditions. The present
      results indicate that the stimulatory effect of Fe deficiency on Cd uptake in
      Ganges may be related to an up-regulation in the expression of genes encoding for
      Fe(2+) uptake, possibly TcIRT1-G.

PMID- 11950986
TI  - Hormone and seed-specific regulation of pea fruit growth.
AB  - Growth of young pea (Pisum sativum) fruit (pericarp) requires developing seeds
      or, in the absence of seeds, treatment with gibberellin (GA) or auxin (4
      chloroindole-3-acetic acid). This study examined the role of seeds and hormones
      in the regulation of cell division and elongation in early pea fruit development.
      Profiling histone H2A and gamma-tonoplast intrinsic protein (TIP) gene expression
      during early fruit development identified the relative contributions of cell
      division and elongation to fruit growth, whereas histological studies identified
      specific zones of cell division and elongation in exocarp, mesocarp, and endocarp
      tissues. Molecular and histological studies showed that maximal cell division was
      from -2 to 2 d after anthesis (DAA) and elongation from 2 to 5 DAA in pea
      pericarp. Maximal increase in pericarp gamma-TIP message level preceded the
      maximal rate of fruit growth and, in general, gamma-TIP mRNA level was useful as
      a qualitative marker for expanding tissue, but not as a quantitative marker for
      cell expansion. Seed removal resulted in rapid decreases in pericarp growth and
      in gamma-TIP and histone H2A message levels. In general, GA and 4-chloroindole-3
      acetic acid maintained these processes in deseeded pericarp similarly to
      pericarps with seeds, and both hormones were required to obtain mesocarp cell
      sizes equivalent to intact fruit. However, GA treatment to deseeded pericarps
      resulted in elevated levels of gamma-TIP mRNA (6 and 7 DAA) when pericarp growth
      and cell enlargement were minimal. Our data support the theory that cell division
      and elongation are developmentally regulated during early pea fruit growth and
      are maintained by the hormonal interaction of GA and auxin.

PMID- 11950985
TI  - Pyruvate,orthophosphate dikinase in leaves and chloroplasts of C(3) plants
      undergoes light-/dark-induced reversible phosphorylation.
AB  - Pyruvate,orthophosphate (Pi) dikinase (PPDK) is best recognized as a
      chloroplastic C(4) cycle enzyme. As one of the key regulatory foci for
      controlling flux through this photosynthetic pathway, it is strictly and
      reversibly regulated by light. This light/dark modulation is mediated by
      reversible phosphorylation of a conserved threonine residue in the active-site
      domain by the PPDK regulatory protein (RP), a bifunctional protein
      kinase/phosphatase. PPDK is also present in C(3) plants, although it has no known
      photosynthetic function. Nevertheless, in this report we show that C(3) PPDK in
      leaves of several angiosperms and in isolated intact spinach (Spinacia oleracea)
      chloroplasts undergoes light-/dark-induced changes in phosphorylation state in a
      manner similar to C(4) dikinase. In addition, the kinetics of this process
      closely resemble the reversible C(4) process, with light-induced
      dephosphorylation occurring rapidly (< or =15 min) and dark-induced
      phosphorylation occurring much more slowly (> or =30-60 min). In intact spinach
      chloroplasts, light-induced dephosphorylation of C(3) PPDK was shown to be
      dependent on exogenous Pi and photosystem II activity but independent of electron
      transfer from photosystem I. These in organello results implicate a role for
      stromal pools of Pi and adenylates in regulating the reversible phosphorylation
      of C(3)-PPDK. Last, we used an in vitro RP assay to directly demonstrate ADP
      dependent PPDK phosphorylation in desalted leaf extracts of the C(3) plants Vicia
      faba and rice (Oryza sativa). We conclude that an RP-like activity mediates the
      light/dark modulation of PPDK phosphorylation state in C(3) leaves and
      chloroplasts and likely represents the ancestral isoform of this unusual and key
      C(4) pathway regulatory "converter" enzyme.

PMID- 11950987
TI  - Pharmacological analysis of nod factor-induced calcium spiking in Medicago
      truncatula. Evidence for the requirement of type IIA calcium pumps and
      phosphoinositide signaling.
AB  - Bacterial Nod factors trigger a number of cellular responses in root hairs of
      compatible legume hosts, which include periodic, transient increases in cytosolic
      calcium levels, termed calcium spiking. We screened 13 pharmaceutical modulators
      of eukaryotic signal transduction for effects on Nod factor-induced calcium
      spiking. The purpose of this screening was 2-fold: to implicate enzymes required
      for Nod factor-induced calcium spiking in Medicago sp., and to identify
      inhibitors of calcium spiking suitable for correlating calcium spiking to other
      Nod factor responses to begin to understand the function of calcium spiking in
      Nod factor signal transduction. 2-Aminoethoxydiphenylborate, caffeine,
      cyclopiazonic acid (CPA), 2,5-di-(t-butyl)-1,4-hydroquinone, and U-73122 inhibit
      Nod factor-induced calcium spiking. CPA and U-73122 are inhibitors of plant type
      IIA calcium pumps and phospholipase C, respectively, and implicate the
      requirement for these enzymes in Nod factor-induced calcium spiking. CPA and U
      73122 inhibit Nod factor-induced calcium spiking robustly at concentrations with
      no apparent toxicity to root hairs, making CPA and U-73122 suitable for testing
      whether calcium spiking is causal to subsequent Nod factor responses.

PMID- 11950988
TI  - Mechanically stimulated TCH3 gene expression in Arabidopsis involves protein
      phosphorylation and EIN6 downstream of calcium.
AB  - Mechanical signals are important both as environmental and endogenous
      developmental cues in plants. Among the quickest measurable responses to
      mechanical stimulation (MS) in plants is the up-regulation of specific genes,
      including TCH3, in Arabidopsis. Little is known about the signaling events and
      components that link perception of mechanical signals to gene expression in
      plants. Calcium has been identified previously as being potentially involved, and
      a role for ethylene has also been suggested. Using the protein kinase inhibitor
      staurosporine, we determined that MS up-regulation of TCH3 expression requires
      protein kinase activity in young Arabidopsis seedlings. Our data from studies on
      the Arabidopsis ein6 mutant demonstrate that the EIN6 protein is also required,
      but that its role in mechanically induced TCH3 expression appears to be
      independent of ethylene. Challenge of seedlings with protein phosphatase
      inhibitors calyculin A and okadaic acid stimulated TCH3 expression even in the
      absence of MS, implying protein phosphatase activity acting to negatively
      regulate TCH3 gene expression. This phosphatase activity acts either downstream
      or independently of EIN6. EIN6 and protein kinase activity, on the other hand,
      operate downstream of calcium to mediate mechanically stimulated TCH3 expression.

PMID- 11950989
TI  - Indole-3-acetic acid metabolism in Lemna gibba undergoes dynamic changes in
      response to growth temperature.
AB  - Auxin is the mobile signal controlling the rate of growth and specific aspects of
      the development of plants. It has been known for over a century that auxins act
      as the messenger linking plant development to specific environmental changes. An
      often overlooked aspect of how this is accomplished is the effect of the
      environment on metabolism of the major plant auxin, indole-3-acetic acid (IAA).
      We have studied the metabolism of IAA in relation to one environmental variable,
      growth temperature. The model system used was an inbred line of the aquatic
      monocot Lemna gibba G-3, 3F7-11 grown at temperatures ranging from 5 degrees C to
      35 degrees C. IAA levels, the rate of IAA turnover, and the patterns of label
      incorporation from IAA precursors were measured using stable isotope-mass
      spectrometric techniques and were evaluated relative to growth at the
      experimental temperatures. IAA levels exhibited unusually high variability in
      plants grown at 15 degrees C and 20 degrees C. Turnover rates were quite rapid
      throughout the range of experimental temperatures except at 25 degrees C, where
      IAA turnover was notably slower. These results suggest that a transition occurred
      over these temperatures for some aspect of IAA metabolism. Analysis of
      [(15)N]anthranilate and [(2)H(5)]tryptophan (Trp) incorporation into IAA showed
      that Trp-dependent biosynthesis predominated at 15 degrees C; however, Trp
      independent biosynthesis of IAA was the major route to IAA at 30 degrees C. The
      effects of growth temperature on auxin levels have been reported previously, but
      no prior studies correlated these effects with which pathway becomes the primary
      one for IAA production.

PMID- 11950990
TI  - Biochemical and molecular inhibition of plastidial carbonic anhydrase reduces the
      incorporation of acetate into lipids in cotton embryos and tobacco cell
      suspensions and leaves.
AB  - Two cDNAs encoding functional carbonic anhydrase (CA) enzymes were recently
      isolated from a non-photosynthetic, cotyledon library of cotton (Gossypium
      hirsutum) seedlings with putative plastid-targeting sequences (GenBank accession
      nos. AF132854 and AF132855). Relative CA transcript abundance and enzyme activity
      increased 9 and 15 times, respectively, in cotton embryos during the maximum
      period of reserve oil accumulation. Specific sulfonamide inhibitors of CA
      activity significantly reduced the rate of [(14)C]acetate incorporation into
      total lipids in cotton embryos in vivo, and in embryo plastids in vitro,
      suggesting a role for CA in plastid lipid biosynthesis. CA inhibitors did not
      affect acetyl-coenzyme A carboxylase activity or total storage protein synthesis.
      Similar results were obtained for two other plant systems: cell suspensions (and
      isolated plastids therefrom) of tobacco (Nicotiana tabacum), and chloroplasts
      isolated from leaves of transgenic CA antisense-suppressed tobacco plants (5% of
      wild-type CA activity). In addition, tobacco cell suspensions treated with the CA
      inhibitor ethoxyzolamide showed a substantial loss of CO(2) compared with
      controls. The rate of [(14)C]acetate incorporation into lipid in cell suspensions
      was reduced by limiting external [CO(2)] (scrubbed air), and this rate was
      further reduced in the presence of ethoxyzolamide. Together, these results
      indicate that a reduction of CA activity (biochemical or molecular inhibition)
      impacts the rate of plant lipid biosynthesis from acetate, perhaps by impairing
      the ability of CA to efficiently "trap" inorganic carbon inside plastids for
      utilization by acetyl-coenzyme A carboxylase and the fatty acid synthesis
      machinery.

PMID- 11950991
TI  - Mutational analysis of the ethylene receptor ETR1. Role of the histidine kinase
      domain in dominant ethylene insensitivity.
AB  - The ethylene receptor family of Arabidopsis consists of five members, one of
      these being ETR1. The N-terminal half of ETR1 contains a hydrophobic domain
      responsible for ethylene binding and membrane localization. The C-terminal half
      of the polypeptide contains domains with homology to histidine (His) kinases and
      response regulators, signaling motifs originally identified in bacteria. The role
      of the His kinase domain in ethylene signaling was examined in planta. For this
      purpose, site-directed mutations were introduced into the full-length wild-type
      ETR1 gene and into etr1-1, a mutant allele that confers dominant ethylene
      insensitivity on plants. The mutant forms of the receptor were expressed in
      Arabidopsis and the transgenic plants characterized for their ethylene responses.
      A mutation that eliminated His kinase activity did not affect the ability of etr1
      1 to confer ethylene insensitivity. A truncated version of etr1-1 that lacks the
      His kinase domain also conferred ethylene insensitivity. Possible mechanisms by
      which a truncated version of etr1-1 could exert dominance are discussed.

PMID- 11950992
TI  - Molecular analysis of signals controlling dormancy and growth in underground
      adventitious buds of leafy spurge.
AB  - Dormancy and subsequent regrowth of adventitious buds is a critical physiological
      process for many perennial plants. We have used the expression of hormone and
      cell cycle-responsive genes as markers to follow this process in leafy spurge
      (Euphorbia esula). In conjunction with earlier studies, we show that loss of
      mature leaves results in decreased sugar levels and increased gibberellin
      perception in underground adventitious buds. Gibberellin is sufficient for
      induction of S phase-specific but not M phase-specific gene expression. Loss of
      both apical and axillary buds or inhibition of polar auxin transport did not
      result in induction of S phase- or M phase-specific gene expression. Loss of
      polar auxin transport was necessary for continuation of the cell cycle and
      further bud development if the S phase was previously initiated.

PMID- 11950993
TI  - A small GTP-binding host protein is required for entry of powdery mildew fungus
      into epidermal cells of barley.
AB  - Small GTP-binding proteins such as those from the RAC family are cytosolic signal
      transduction proteins that often are involved in processing of extracellular
      stimuli. Plant RAC proteins are implicated in regulation of plant cell
      architecture, secondary wall formation, meristem signaling, and defense against
      pathogens. We isolated a RacB homolog from barley (Hordeum vulgare) to study its
      role in resistance to the barley powdery mildew fungus (Blumeria graminis f.sp.
      hordei). RacB was constitutively expressed in the barley epidermis and its
      expression level was not strongly influenced by inoculation with B. graminis.
      However, after biolistic bombardment of barley leaf segments with RacB-double
      stranded RNA, sequence-specific RNA interference with RacB function inhibited
      fungal haustorium establishment in a cell-autonomous and genotype-specific
      manner. Mutants compromised in function of the Mlo wild-type gene and the Ror1
      gene (genotype mlo5 ror1) that are moderately susceptible to B. graminis showed
      no alteration in powdery mildew resistance upon RacB-specific RNA interference.
      Thus, the phenotype, induced by RacB-specific RNA interference, was apparently
      dependent on the same processes as mlo5-mediated broad resistance, which is
      suppressed by ror1. We conclude that an RAC small GTP-binding protein is required
      for successful fungal haustorium establishment and that this function may be
      linked to MLO-associated functions.

PMID- 11950995
TI  - Regulation by polyamines of ornithine decarboxylase activity and cell division in
      the unicellular green alga Chlamydomonas reinhardtii.
AB  - Polyamines are required for cell growth and cell division in eukaryotic and
      prokaryotic organisms. In the unicellular green alga Chlamydomonas reinhardtii,
      biosynthesis of the commonly occurring polyamines (putrescine, spermidine, and
      spermine) is dependent on the activity of ornithine decarboxylase (ODC, EC
      4.1.1.17) catalyzing the formation of putrescine, which is the precursor of the
      other two polyamines. In synchronized C. reinhardtii cultures, transition to the
      cell division phase was preceded by a 4-fold increase in ODC activity and a 10-
      and a 20-fold increase, respectively, in the putrescine and spermidine levels.
      Spermine, however, could not be detected in C. reinhardtii cells. Exogenous
      polyamines caused a decrease in ODC activity. Addition of spermine, but not of
      spermidine or putrescine, abolished the transition to the cell division phase
      when applied 7 to 8 h after beginning of the light (growth) phase. Most of the
      cells had already doubled their cell mass after this growth period. The spermine
      induced cell cycle arrest could be overcome by subsequent addition of spermidine
      or putrescine. The conclusion that spermine affects cell division via a decreased
      spermidine level was corroborated by the findings that spermine caused a decrease
      in the putrescine and spermidine levels and that cell divisions also could be
      prevented by inhibitors of S-adenosyl-methionine decarboxylase and spermidine
      synthase, respectively, added 8 h after beginning of the growth period. Because
      protein synthesis was not decreased by addition of spermine under our
      experimental conditions, we conclude that spermidine affects the transition to
      the cell division phase directly rather than via protein biosynthesis.

PMID- 11950994
TI  - Genetic manipulation of the metabolism of polyamines in poplar cells. The
      regulation of putrescine catabolism.
AB  - We investigated the catabolism of putrescine (Put) in a non-transgenic (NT) and a
      transgenic cell line of poplar (Populus nigra x maximowiczii) expressing a mouse
      (Mus musculus) ornithine (Orn) decarboxylase (odc) cDNA. The transgenic cells
      produce 3- to 4-fold higher amounts of Put than the NT cells. The rate of loss of
      Put from the cells and the initial half-life of cellular Put were determined by
      feeding the cells with [U-(14)C]Orn and [1,4-(14)C]Put as precursors and
      following the loss of [(14)C]Put in the cells at various times after transfer to
      label-free medium. The amount of Put converted into spermidine as well as the
      loss of Put per gram fresh weight were significantly higher in the transgenic
      cells than the NT cells. The initial half-life of exogenously supplied [(14)C]Put
      was not significantly different in the two cell lines. The activity of diamine
      oxidase, the major enzyme involved in Put catabolism, was comparable in the two
      cell lines even though the Put content of the transgenic cells was severalfold
      higher than the NT cells. It is concluded that in poplar cells: (a) exogenously
      supplied Orn enters the cells and is rapidly converted into Put, (b) the rate of
      Put catabolism is proportional to the rate of its biosynthesis, and (c) the
      increased Put degradation occurs without significant changes in the activity of
      diamine oxidase.

PMID- 11950996
TI  - Metabolizable and non-metabolizable sugars activate different signal transduction
      pathways in tomato.
AB  - To gain insight into the regulatory mechanisms of sugar signaling in plants, the
      effect of derivatives of the transport sugar sucrose (Suc), the Suc isomers
      palatinose and turanose, and the Suc analog fluoro-Suc were tested. Photo
      autotrophic suspension culture cells of tomato (Lycopersicon peruvianum) were
      used to study their effect on the regulation of marker genes of source and sink
      metabolism, photosynthesis, and the activation of mitogen-activated protein
      kinases (MAPKs). Suc and glucose (Glc) resulted in reverse regulation of source
      and sink metabolism. Whereas the mRNA level of extracellular invertase (Lin6) was
      induced, the transcript level of small subunit of ribulose bisphosphate
      carboxylase (RbcS) was repressed. In contrast, turanose, palatinose, and fluoro
      Suc only rapidly induced Lin6 mRNA level, whereas the transcript level of RbcS
      was not affected. The differential effect of the metabolizable and non
      metabolizable sugars on RbcS mRNA regulation was reflected by the fact that only
      Suc and Glc inhibited photosynthesis and chlorophyll fluorescence. The activation
      of different signal transduction pathways by sugars was further supported by the
      analysis of the activation of MAPKs. MAPK activity was found to be strongly
      activated by turanose, palatinose, and fluoro-Suc, but not by Suc and Glc. To
      analyze the role of sugars in relation to pathogen perception, an elicitor
      preparation of Fusarium oxysporum lycopersici was used. The strong activation of
      MAPKs and the fast and transient induction of Lin6 expresssion by the fungal
      elicitor resembles the effect of turanose, palatinose, and fluoro-Suc and
      indicates that non-metabolizable sugars are sensed as stress-related stimuli.

PMID- 11950997
TI  - Evolution of sucrose synthesis.
AB  - Cyanobacteria and proteobacteria (purple bacteria) are the only prokaryotes known
      to synthesize sucrose (Suc). Suc-P synthase, Suc-phosphatase (SPP), and Suc
      synthase activities have previously been detected in several cyanobacteria, and
      genes coding for Suc-P synthase (sps) and Suc synthase (sus) have been cloned
      from Synechocystis sp. PCC 6803 and Anabaena (Nostoc) spp., respectively. An open
      reading frame in the Synechocystis genome encodes a predicted 27-kD polypeptide
      that shows homology to the maize (Zea mays) SPP. Heterologous expression of this
      putative spp gene in Escherichia coli, reported here, confirmed that this open
      reading frame encodes a functional SPP enzyme. The Synechocystis SPP is highly
      specific for Suc-6(F)-P (K(m) = 7.5 microM) and is Mg(2+) dependent (K(a) = 70
      microM), with a specific activity of 46 micromol min(-1) mg(-1) protein. Like the
      maize SPP, the Synechocystis SPP belongs to the haloacid dehalogenase superfamily
      of phosphatases/hydrolases. Searches of sequenced microbial genomes revealed
      homologs of the Synechocystis sps gene in several other cyanobacteria (Nostoc
      punctiforme, Prochlorococcus marinus strains MED4 and MIT9313, and Synechococcus
      sp. WH8012), and in three proteobacteria (Acidithiobacillus ferrooxidans,
      Magnetococcus sp. MC1, and Nitrosomonas europaea). Homologs of the Synechocystis
      spp gene were found in Magnetococcus sp. MC1 and N. punctiforme, and of the
      Anabaena sus gene in N. punctiforme and N. europaea. From analysis of these
      sequences, it is suggested that Suc synthesis originated in the proteobacteria or
      a common ancestor of the proteobacteria and cyanobacteria.

PMID- 11951000
TI  - Aging. Genomic priorities in aging.

PMID- 11950999
TI  - Direct recognition of cytomegalovirus by activating and inhibitory NK cell
      receptors.
AB  - Natural killer (NK) cells express inhibitory receptors for major
      histocompatibility complex (MHC) class I antigens, preventing attack against
      healthy cells. Mouse cytomegalovirus (MCMV) encodes an MHC-like protein (m157)
      that binds to an inhibitory NK cell receptor in certain MCMV-susceptible mice. In
      MCMV-resistant mice, this viral protein engages a related activating receptor
      (Ly49H) and confers host protection. These activating and inhibitory receptors
      are highly homologous, suggesting the possibility that one evolved from the other
      in response to selective pressure imposed by the pathogen.

PMID- 11950998
TI  - Premature aging in mice deficient in DNA repair and transcription.
AB  - One of the factors postulated to drive the aging process is the accumulation of
      DNA damage. Here, we provide strong support for this hypothesis by describing
      studies of mice with a mutation in XPD, a gene encoding a DNA helicase that
      functions in both repair and transcription and that is mutated in the human
      disorder trichothiodystrophy (TTD). TTD mice were found to exhibit many symptoms
      of premature aging, including osteoporosis and kyphosis, osteosclerosis, early
      greying, cachexia, infertility, and reduced life-span. TTD mice carrying an
      additional mutation in XPA, which enhances the DNA repair defect, showed a
      greatly accelerated aging phenotype, which correlated with an increased cellular
      sensitivity to oxidative DNA damage. We hypothesize that aging in TTD mice is
      caused by unrepaired DNA damage that compromises transcription, leading to
      functional inactivation of critical genes and enhanced apoptosis.

PMID- 11951001
TI  - Binary asteroids in the near-Earth object population.
AB  - Radar images of near-Earth asteroid 2000 DP107 show that it is composed of an
      approximately 800-meter-diameter primary and an approximately 300-meter-diameter
      secondary revolving around their common center of mass. The orbital period of
      1.755 +/- 0.007 days and semimajor axis of 2620 +/- 160 meters constrain the
      total mass of the system to 4.6 +/- 0.5 x 10(11) kilograms and the bulk density
      of the primary to 1.7 +/- 1.1 grams per cubic centimeter. This system and other
      binary near-Earth asteroids have spheroidal primaries spinning near the breakup
      point for strengthless bodies, suggesting that the binaries formed by spin-up and
      fission, probably as a result of tidal disruption during close planetary
      encounters. About 16% of near-Earth asteroids larger than 200 meters in diameter
      may be binary systems.

PMID- 11951003
TI  - Minorities in the scientific workforce.

PMID- 11951002
TI  - Questioning the evidence for genetic recombination in the 1918 "Spanish flu"
      virus.

PMID- 11951004
TI  - Climate change. Battle over IPCC chair renews debate on U.S. climate policy.

PMID- 11951005
TI  - Climate change. White House shakes up U.S. program.

PMID- 11951006
TI  - Primate evolution. Gene activity clocks brain's fast evolution.

PMID- 11951008
TI  - Mexican maize. Transgene data deemed unconvincing.

PMID- 11951007
TI  - Archaeology. Early cowboys herded cattle in Africa.

PMID- 11951009
TI  - U.S. export controls. Rules eased on satellite projects.

PMID- 11951011
TI  - Astronomy. If it quarks like a star, it must be...strange?

PMID- 11951010
TI  - Embryonic stem cells. Australian agreement allows new lines.

PMID- 11951012
TI  - Genome Canada. New awards bolster Canada's global role.

PMID- 11951013
TI  - Toxicology. Fruit bats linked to mystery disease.

PMID- 11951014
TI  - Cardiovascular disease. Does inflammation cut to the heart of the matter?

PMID- 11951015
TI  - Marine ecology. Picturing the perfect preserve.

PMID- 11951016
TI  - Technology. Microchips that never forget.

PMID- 11951017
TI  - Technology. A bit of this and that.

PMID- 11951018
TI  - Materials science. Biology reveals new ways to hold on tight.

PMID- 11951019
TI  - Embryonic stem cells. The debate in Germany.

PMID- 11951020
TI  - Virology. Poliomyelitis eradication--a dangerous endgame.

PMID- 11951021
TI  - Chemistry. Catalytic degradation of chlorinated phenols.

PMID- 11951022
TI  - Planetary science. A new solar system basalt.

PMID- 11951024
TI  - Plant biology. MADS-box genes reach maturity.

PMID- 11951023
TI  - Immunology. Pathogen surveillance--the flies have it.

PMID- 11951025
TI  - Applied optics. New ways to guide light.

PMID- 11951026
TI  - Paleoclimate. Corals, chemistry, and climate.

PMID- 11951027
TI  - Virology. Rafting with Ebola.

PMID- 11951028
TI  - Thermal barrier coatings for gas-turbine engine applications.
AB  - Hundreds of different types of coatings are used to protect a variety of
      structural engineering materials from corrosion, wear, and erosion, and to
      provide lubrication and thermal insulation. Of all these, thermal barrier
      coatings (TBCs) have the most complex structure and must operate in the most
      demanding high-temperature environment of aircraft and industrial gas-turbine
      engines. TBCs, which comprise metal and ceramic multilayers, insulate turbine and
      combustor engine components from the hot gas stream, and improve the durability
      and energy efficiency of these engines. Improvements in TBCs will require a
      better understanding of the complex changes in their structure and properties
      that occur under operating conditions that lead to their failure. The structure,
      properties, and failure mechanisms of TBCs are herein reviewed, together with a
      discussion of current limitations and future opportunities.

PMID- 11951029
TI  - Arabidopsis, the Rosetta stone of flowering time?
AB  - Multiple environmental and endogenous inputs regulate when plants flower. The
      molecular genetic dissection of flowering time control in Arabidopsis has
      identified an integrated network of pathways that quantitatively control the
      timing of this developmental switch. This framework provides the basis to
      understand the evolution of different reproductive strategies and how floral
      pathways interact through seasonal progression.

PMID- 11951032
TI  - The danger model: a renewed sense of self.
AB  - For over 50 years immunologists have based their thoughts, experiments, and
      clinical treatments on the idea that the immune system functions by making a
      distinction between self and nonself. Although this paradigm has often served us
      well, years of detailed examination have revealed a number of inherent problems.
      This Viewpoint outlines a model of immunity based on the idea that the immune
      system is more concerned with entities that do damage than with those that are
      foreign.

PMID- 11951031
TI  - Decoding the patterns of self and nonself by the innate immune system.
AB  - The innate immune system evolved several strategies of self/nonself
      discrimination that are based on the recognition of molecular patterns
      demarcating infectious nonself, as well as normal and abnormal self. These
      patterns are deciphered by receptors that either induce or inhibit an immune
      response, depending on the meaning of these signals.

PMID- 11951033
TI  - Recognition and rejection of self in plant reproduction.
AB  - Plant self-incompatibility (SI) systems are unique among self/nonself recognition
      systems in being based on the recognition of self rather than nonself. SI in
      crucifer species is controlled by highly polymorphic and co-evolving genes linked
      in a complex. Self recognition is based on allele-specific interactions between
      stigma receptors and pollen ligands that result in the arrest of pollen tube
      development. Commonalities and differences between SI and other self/nonself
      discrimination systems are discussed.

PMID- 11951034
TI  - Self-representation in nervous systems.
AB  - The brain's earliest self-representational capacities arose as evolution found
      neural network solutions for coordinating and regulating inner-body signals,
      thereby improving behavioral strategies. Additional flexibility in organizing
      coherent behavioral options emerges from neural models that represent some of the
      brain's inner states as states of its body, while representing other signals as
      perceptions of the external world. Brains manipulate inner models to predict the
      distinct consequences in the external world of distinct behavioral options. The
      self thus turns out to be identifiable not with a nonphysical soul, but rather
      with a set of representational capacities of the physical brain.

PMID- 11951035
TI  - The many selves of social insects.
AB  - Social insects show multiple levels of self identity. Most individuals are
      sterile workers who selflessly labor for their colony, which is often viewed as a
      superorganism. The superorganism protects itself with colony recognition systems
      based on learned odors, typically cuticular hydrocarbons. Transfer of these odors
      within the colony obscures separate clan identities. Residual individual
      interests do appear to cause conflicts within colonies over sex ratio, male
      production, caste, and reproductive dominance. However, genomic imprinting theory
      predicts that the individual's maternal and paternal genes will evolve separate
      infraorganismal identities, perhaps leaving virtually no coherent individual
      identity.

PMID- 11951036
TI  - Human cloning and our sense of self.
AB  - This Viewpoint formulates and responds to three lines of argument concerning
      human reproductive cloning's potential to undermine our sense of self or
      identity. First, cloning would undermine our sense of individuality or
      uniqueness. But it could only undermine our genetic uniqueness, not our full
      individuality. Second, cloning would undermine the value or worth of human
      beings. But it would not make individuals replaceable or of any less moral worth.
      Third, a clone's freedom or autonomy to construct his or her own life would be
      undermined by the presence of an earlier twin. But only a mistaken belief in
      genetic determinism supports this feared loss of freedom.

PMID- 11951037
TI  - Dietary restriction in long-lived dwarf flies.

PMID- 11951038
TI  - Formation of the three-ring structure around supernova 1987A.
AB  - From a magnetohydrodynamic simulation, we reproduce a three-ring structure in the
      circumstellar space of the supernova (SN) 1987A observed by the Hubble Space
      Telescope. When a star develops from a red supergiant (RSG) to a blue supergiant
      (BSG) just before the SN explosion, a wind-wind interaction occurs between the
      slow stellar wind from the RSG and the subsequent fast stellar wind from the BSG.
      This process is simulated numerically under an assumption that the density and
      velocity distributions around the RSG are anisotropic owing to the existence of
      toroidal magnetic field and coronal holes. The three rings with observed size and
      position are reproduced by the magnetic pinch effect and amplification of initial
      density asymmetry through the dynamical interaction.

PMID- 11951039
TI  - Fabrication of a cylindrical display by patterned assembly.
AB  - We demonstrate the patterned assembly of integrated semiconductor devices onto
      planar, flexible, and curved substrates on the basis of capillary interactions
      involving liquid solder. The substrates presented patterned, solder-coated areas
      that acted both as receptors for the components of the device during its assembly
      and as electrical connections during its operation. The components were suspended
      in water and agitated gently. Minimization of the free energy of the solder-water
      interface provided the driving force for the assembly. One hundred and thirteen
      GaAlAs light-emitting diodes with a chip size of 280 micrometers were fabricated
      into a prototype cylindrical display. It was also possible to assemble 1500
      silicon cubes, on an area of 5 square centimeters, in less than 3 minutes, with a
      defect rate of approximately 2%.

PMID- 11951041
TI  - Organic molecules acting as templates on metal surfaces.
AB  - The electronic connection of single molecules to nanoelectrodes on a surface is a
      basic, unsolved problem in the emerging field of molecular nanoelectronics. By
      means of variable temperature scanning tunneling microscopy, we show that an
      organic molecule (C90H98), known as the Lander, can cause the rearrangement of
      atoms on a Cu(110) surface. These molecules act as templates accommodating metal
      atoms at the step edges of the copper substrate, forming metallic nanostructures
      (0.75 nanometers wide and 1.85 nanometers long) that are adapted to the
      dimensions of the molecule.

PMID- 11951040
TI  - Rapid total destruction of chlorophenols by activated hydrogen peroxide.
AB  - A practical, inexpensive, green chemical process for degrading environmental
      pollutants is greatly needed, especially for persistent chlorinated pollutants.
      Here we describe the activation of hydrogen peroxide by tetraamidomacrocylic
      ligand (TAML) iron catalysts, to destroy the priority pollutants
      pentachlorophenol (PCP) and 2,4,6-trichlorophenol (TCP). In water, in minutes,
      under ambient conditions of temperature and pressure, PCP and TCP are completely
      destroyed at catalyst:substrate ratios of 1:715 and 1:2000, respectively. The
      fate of about 90% of the carbon and about 99% of the chlorine has been determined
      in each case. Neither dioxins nor any other toxic compounds are detectable
      products, and the catalysts themselves show low toxicity.

PMID- 11951042
TI  - A new source of basaltic meteorites inferred from Northwest Africa 011.
AB  - Eucrites are a class of basaltic meteorites that share common mineralogical,
      isotopic, and chemical properties and are thought to have been derived from the
      same parent body, possibly asteroid 4 Vesta. The texture, mineralogy, and noble
      gas data of the recently recovered meteorite, Northwest Africa (NWA) 011, are
      similar to those of basaltic eucrites. However, the oxygen isotopic composition
      of NWA011 is different from that of other eucrites, indicating that NWA011 may be
      derived from a different parent body. The presence of basaltic meteorites with
      variable oxygen isotopic composition suggests the occurrence of multiple basaltic
      meteorite parent bodies, perhaps similar to 4 Vesta, in the early solar system.

PMID- 11951043
TI  - African pastoralism: genetic imprints of origins and migrations.
AB  - The genetic history of African cattle pastoralism is controversial and poorly
      understood. We reveal the genetic signatures of its origins, secondary movements,
      and differentiation through the study of 15 microsatellite loci in 50 indigenous
      cattle breeds spanning the present cattle distribution in Africa. The earliest
      cattle originated within the African continent, but Near East and European
      genetic influences are also identified. The initial expansion of African Bos
      taurus was likely from a single region of origin. It reached the southern part of
      the continent by following an eastern route rather than a western one. The B.
      indicus genetic influence shows a major entry point through the Horn and the East
      Coast of Africa and two modes of introgression into the continent.

PMID- 11951044
TI  - Intra- and interspecific variation in primate gene expression patterns.
AB  - Although humans and their closest evolutionary relatives, the chimpanzees, are
      98.7% identical in their genomic DNA sequences, they differ in many
      morphological, behavioral, and cognitive aspects. The underlying genetic basis of
      many of these differences may be altered gene expression. We have compared the
      transcriptome in blood leukocytes, liver, and brain of humans, chimpanzees,
      orangutans, and macaques using microarrays, as well as protein expression
      patterns of humans and chimpanzees using two-dimensional gel electrophoresis. We
      also studied three mouse species that are approximately as related to each other
      as are humans, chimpanzees, and orangutans. We identified species-specific gene
      expression patterns indicating that changes in protein and gene expression have
      been particularly pronounced in the human brain.

PMID- 11951045
TI  - A MADS-box gene necessary for fruit ripening at the tomato ripening-inhibitor
      (rin) locus.
AB  - Tomato plants harboring the ripening-inhibitor (rin) mutation yield fruits that
      fail to ripen. Additionally, rin plants display enlarged sepals and loss of
      inflorescence determinacy. Positional cloning of the rin locus revealed two
      tandem MADS-box genes (LeMADS-RIN and LeMADS-MC), whose expression patterns
      suggested roles in fruit ripening and sepal development, respectively. The rin
      mutation alters expression of both genes. Gene repression and mutant
      complementation demonstrate that LeMADS-RIN regulates ripening, whereas LeMADS-MC
      affects sepal development and inflorescence determinacy. LeMADS-RIN demonstrates
      an agriculturally important function of plant MADS-box genes and provides
      molecular insight into nonhormonal (developmental) regulation of ripening.

PMID- 11951046
TI  - Regulation of mitochondrial biogenesis in skeletal muscle by CaMK.
AB  - Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle
      and enhances muscle oxidative capacity, but the signaling mechanisms involved are
      poorly understood. To investigate this adaptive process, we generated transgenic
      mice that selectively express in skeletal muscle a constitutively active form of
      calcium/calmodulin-dependent protein kinase IV (CaMKIV*). Skeletal muscles from
      these mice showed augmented mitochondrial DNA replication and mitochondrial
      biogenesis, up-regulation of mitochondrial enzymes involved in fatty acid
      metabolism and electron transport, and reduced susceptibility to fatigue during
      repetitive contractions. CaMK induced expression of peroxisome proliferator
      activated receptor gamma coactivator 1 (PGC-1), a master regulator of
      mitochondrial biogenesis in vivo, and activated the PGC-1 gene promoter in
      cultured myocytes. Thus, a calcium-regulated signaling pathway controls
      mitochondrial biogenesis in mammalian cells.

PMID- 11951047
TI  - Structure of a cofactor-deficient nitrogenase MoFe protein.
AB  - One of the most complex biosynthetic processes in metallobiochemistry is the
      assembly of nitrogenase, the key enzyme in biological nitrogen fixation. We
      describe here the crystal structure of an iron-molybdenum cofactor-deficient form
      of the nitrogenase MoFe protein, into which the cofactor is inserted in the final
      step of MoFe protein assembly. The MoFe protein folds as a heterotetramer
      containing two copies each of the homologous alpha and beta subunits. In this
      structure, one of the three alpha subunit domains exhibits a substantially
      changed conformation, whereas the rest of the protein remains essentially
      unchanged. A predominantly positively charged funnel is revealed; this funnel is
      of sufficient size to accommodate insertion of the negatively charged cofactor.

PMID- 11951048
TI  - Persistence of tight junctions and changes in apical structures and protein
      expression in choroid plexus epithelium of rats after short-term head-down tilt.
AB  - Major alterations of choroidal cell polarity and protein expression were
      previously shown to be induced in rats by long-term adaptation to space flight
      (14 days aboard a space shuttle) or anti-orthostatic suspension (14 and 28 days)
      performed by tilting rats head-down (i.e. using a ground-based model known to
      simulate several effects of weightlessness). In rabbits, it was hypothesized that
      the blood-CSF barrier was opened in choroid plexus, after a short head-down
      suspension. To understand the early responses to fluid shifts induced by head
      down tilts and evaluate the tightness of the choroidal junctions, we have
      investigated the effects of acute adaptations to anti-orthostatic restraints,
      using hindlimb-suspended Sprague-Dawley and Wistar rats. Ultrastructural and
      immunocytochemical studies were performed on choroid plexuses from lateral, third
      and fourth ventricles, after 30, 90 and 180 minutes of head-down tilt.
      Alterations were not perceptible at the level of choroidal tight junctions, as
      shown by freeze-fracture, claudin-1 and ZO-1 immunolocalizations and conventional
      electron microscopy, after intravenous injection of cytochrome C. The apical
      surface of choroidal cells was clearly more affected. Microvilli were longer and
      thinner and ezrin was over-expressed during all the periods of time considered,
      showing an early cytoskeletal response. Several proteins involved in the
      choroidal production of cerebrospinal fluid (sodium-potassium ATPase, carbonic
      anhydrase II, aquaporin 1) appeared first increased (30 minutes after the tilt),
      and then, returned to the control level or were lowered (after a 3-hour head-down
      suspension). Although head-down tilts do not seem to damage the blood
      cerebrospinal fluid barrier in choroid plexus, it seemed that the expression of
      several apical proteins is affected very early.

PMID- 11951049
TI  - Experimental retinal detachment causes widespread and multilayered degeneration
      in rabbit retina.
AB  - Retinal detachment remains one of the most frequent causes of visual impairment
      in humans, even after ophthalmoscopically successful retinal reattachment. This
      study was aimed at monitoring (ultra-) structural alterations of retinae of
      rabbits after experimental detachment. A surgical procedure was used to produce
      local retinal detachments in rabbit eyes similar to the typical lesions in human
      patients. At various periods after detachment, the detached retinal area as well
      as neighbouring attached regions were studied by light and electron microscopy.
      In addition to the well-known degeneration of photoreceptor cells in the detached
      retina, the following progressive alterations were observed, (i) in both the
      detached and the attached regions, an incomplete but severe loss of ganglion cell
      axons occurs; (ii) there is considerable ganglion cell death, particularly in the
      detached area; (iii) even in the attached retina distant from the detachment,
      small adherent groups of photoreceptor cells degenerate; (iv) these photoreceptor
      cells degenerate in an atypical sequence, with severely destructed somata and
      inner segments but well-maintained outer segments; and (v) the severe loss of
      retinal neurons is not accompanied by any significant loss of Muller (glial)
      cells. It is noteworthy that the described progressive (and probably irreparable)
      retinal destructions occur also in the attached retina, and may account for
      visual impairment in strikingly large areas of the visual field, even after
      retinal reattachment.

PMID- 11951050
TI  - Proliferation and death of cultured fetal neocortical neurons: effects of ethanol
      on the dynamics of cell growth.
AB  - Neuronal number in the mature CNS is determined by the balance of cell
      proliferation and death. The effects of ethanol on cell proliferation and death
      were examined in primary cultures of neocortical neurons derived from 16-day-old
      rat fetuses. The cells were treated with ethanol (0 or 400 mg/dl) and examined
      for (1) immunohistochemical identity, (2) cell cycle kinetics using a cumulative
      bromodeoxyuridine labeling technique, (3) viable cell number via a trypan blue
      assay, and (4) the incidence of cell death with terminal deoxy-nucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) and caspase 3
      immunhistochemistry. After two days in culture, most (>85%) cells expressed a
      neuron-specific antigen(s) whether or not ethanol was added to the culture
      medium. Ethanol affected the proliferation of the cultured cells, e.g., the
      length of the cell cycle was greater in the ethanol-treated cells than in
      controls. The number of trypan blue-negative (viable) cells was profoundly
      decreased by ethanol exposure. This decrease was accompanied by increases in the
      frequencies of TUNEL- and caspase 3-positive cells and of cells exhibiting
      nuclear condensations. Thus, ethanol decreases the number of viable cells in
      vitro by slowing cell proliferation and increasing the incidence of cell death.
      The expression of the death indices in untreated cultures is most consistent with
      a single (apoptotic) pathway of cell death, rather than simultaneous apoptotic
      and necrotic modes of death. Furthermore, it appears that ethanol initiates an
      apoptotic death among cultured cortical neurons.

PMID- 11951051
TI  - Expression of the group I metabotropic glutamate receptor in the hippocampus of
      patients with mesial temporal lobe epilepsy.
AB  - Immunocytochemical studies at light and electron microscopic levels in hippocampi
      of patients with mesial temporal lobe epilepsy showed mGluR1 and mGluR5
      immunoreactivity in the molecular layer of the dentate gyrus and CA1 area,
      especially at the border between stratum oriens and alveus. By electron
      microscopy, degenerating neuronal elements were found in all areas studied. There
      were glial filamentous tangles which appeared similar to intranuclear inclusions
      in astrocytes in all areas studied. Reactive product for mGluR1 was localised
      only in post-synaptic elements. However, mGluR5 immunoreactivity was demonstrated
      in both post- and pre-synaptic elements in the molecular layer of the dentate
      gyrus and CA1 area. Reactive product for mGluR5 was also demonstrated in
      astrocytes and in the periphery of fibrillary tangles. We postulate that in
      patients with mesial temporal lobe epilepsy, mGluR1 may increase hippocampal
      excitability through postsynaptic activation, and mGluR5 may do so through both
      pre- and post-synaptic mechanisms.

PMID- 11951052
TI  - Reelin in the extracellular matrix and dendritic spines of the cortex and
      hippocampus: a comparison between wild type and heterozygous reeler mice by
      immunoelectron microscopy.
AB  - Reelin is a glycoprotein ( approximately 400 kDa) secreted by GABAergic neurons
      into the extracellular matrix of the neocortex and hippocampus as well as other
      areas of adult rodent and nonhuman primate brains. Recent findings indicate that
      the heterozygote reeler mouse (haploinsufficient for the reeler gene) shares
      several neurochemical and behavioral abnormalities with schizophrenia and bipolar
      disorder with mania. These include (1) a downregulation of both reelin mRNA and
      the translated proteins, (2) a decrease in the number of dendritic spines in
      cortical and hippocampal neurons, (3) a concomitant increase in the packing
      density of cortical pyramidal neurons, and (4) an age-dependent decrease in
      prepulse inhibition of startle. Interestingly, the heterozygous reeler mouse does
      not exhibit the unstable gait or the neuroanatomy characteristic of the null
      mutant reeler mouse. Immunocytochemical studies of the expression of reelin in
      mice have been primarily limited to light microscopy. In this study we present
      new immunoelectron microscopy data that delineates the subcellular localization
      of reelin in the cortex and hippocampus of the wild-type mouse, and compares
      these results to reelin expression in the heterozygous reeler mouse. In
      discontinuous areas of cortical layers I and II and the inner blade area of the
      dentate gyrus of the wild type mouse, extracellular reelin is associated with
      dendrites and dendritic spine postsynaptic specializations. Similar associations
      have been detected in the CA1 stratum oriens and other areas of the hippocampus.
      In the hippocampus, reelin expression is more expansive and more widespread than
      in cortical layers I and II. In contrast, extracellular reelin immunoreactivity
      is greatly diminished in all areas examined in the heterozygous reeler mouse.
      However, some cell bodies of GABAergic neurons in the cortex and hippocampus
      demonstrate an increased accumulation of reelin in the Golgi and endoplasmic
      reticulum. We suggest that in the heterozygous reeler mouse a downregulation of
      reelin biosynthesis results in a decreased rate of secretion into the
      extracellular space. This inhibits dendritic spine maturation and plasticity and
      leads to dissociation of dendritic postsynaptic density integrity and atrophy of
      spines. We speculate that the haploinsufficient reeler mouse may provide a model
      for future studies of the role of reelin, as it may be related to psychosis
      vulnerability.

PMID- 11951053
TI  - Glutamatergic components of the retrosplenial granular cortex in the rat.
AB  - The ultrastructural characteristics, distribution and synaptic relationships of
      identified, glutamate-enriched thalamocortical axon terminals and cell bodies in
      the retrosplenial granular cortex of adult rats is described and compared with
      GABA-containing terminals and cell bodies, using postembedding immunogold
      immunohistochemistry and transmission electron microscopy in animals with
      injections of cholera toxin- horseradish peroxidase (CT-HRP) into the anterior
      thalamic nuclei. Anterogradely labelled terminals, identified by semi-crystalline
      deposits of HRP reaction product, were approximately 1 microm in diameter,
      contained round, clear synaptic vesicles, and established asymmetric (Gray type
      I) synaptic contacts with dendritic spines and small dendrites, some containing
      HRP reaction product, identifying them as dendrites of corticothalamic projection
      neurons. The highest densities of immunogold particles following glutamate
      immunostaining were found over such axon terminals and over similar axon
      terminals devoid of HRP reaction product. In serial sections immunoreacted for
      GABA, these axon terminals were unlabelled, whereas other axon terminals,
      establishing symmetric (Gray type II) synapses were heavily labelled. Cell bodies
      of putative pyramidal neurons, containing retrograde HRP label, were numerous in
      layers V-VI; some were also present in layers I-III. Most were overlain by high
      densities of gold particles in glutamate but not in GABA immunoreacted sections.
      These findings provide evidence that the terminals of projection neurons make
      synaptic contact with dendrites and dendritic spines in the ipsilateral
      retrosplenial granular cortex and that their targets include the dendrites of
      presumptive glutamatergic corticothalamic projection neurons.

PMID- 11951054
TI  - Is (90)Y-DOTATOC treatment for neuroendocrine tumours safe?

PMID- 11951055
TI  - Nefiracetam ameliorates associative learning impairment in the scopolamine
      injected older rabbit.
AB  - BACKGROUND: The cognition-enhancing drug, nefiracetam, is in Phase III clinical
      trials to treat memory impairment in Alzheimer's disease (AD). Nefiracetam
      ameliorates acquisition of delay eyeblink classical conditioning in older
      rabbits, a form of associative learning with striking behavioral and
      neurobiological similarities in rabbits and humans. In both species, delay
      eyeblink conditioning engages the septo-hippocampal cholinergic system and is
      disrupted when the cholinergic system is antagonized. Delay eyeblink classical
      conditioning is impaired in normal aging and severely disrupted in AD.
      MATERIAL/METHODS: To test further the efficacy of nefiracetam in an animal model
      that mimics some of the neurobiological and behavioral effects present in AD, we
      tested 56 older rabbits assigned to 7 treatment groups in the 750 ms delay
      eyeblink conditioning procedure. Older rabbits were injected with 1.5 mg/kg
      scopolamine to simulate disruption of the cholinergic system in AD. Three doses
      of nefiracetam (5, 10, or 15 mg/kg) were also injected in older rabbits receiving
      1.5 mg/kg scopolamine. Control groups were treated with 1.5 mg/kg scopolamine +
      vehicle, vehicle alone, or explicitly unpaired presentations of conditioning
      stimuli and vehicle or 1.5 mg/kg scopolamine + 15 mg/kg nefiracetam. RESULTS:
      Rabbits injected with 1.5 mg/kg scopolamine alone were impaired, but a dose of 15
      mg/kg nefiracetam reversed significantly the behavioral impairment. CONCLUSIONS:
      Nefiracetam had ameliorating effects on a task impaired in AD in an animal model
      of AD: older rabbits with cholinergic system antagonism.

PMID- 11951056
TI  - Percutaneous implantation of a biological valve in the aorta to treat aortic
      valve insufficiency -- a sheep study.
AB  - BACKGROUND: Historically, the surgical implantation of a mechanical valve in the
      descending aorta permitted the reduction of regurgitant flow in chronic aortic
      insufficiency. Long term clinical results were excellent but with the development
      of the pump oxygenators, orthotopic valvar replacement has become the
      conventional treatment of aortic valve diseases. We wanted to reconsider the
      ectopic position in sheep using a new percutaneous technique. MATERIAL/METHODS: A
      biological valve harvested from a bovine jugular vein was sutured into a vascular
      stent. After the creation of a severe aortic insufficiency, the valved stent was
      percutaneously implanted according to standard stent placement techniques.
      Hemodynamic and angiographic evaluations were carried out during the procedure;
      finally, anatomic evaluation was performed. RESULTS: A severe aortic
      insufficiency was created in all animals (9/9). 3 had a single stent in the
      descending aorta and 3 had an additional stent in the brachiocephalic trunk. A
      control group of 3 animals had no valve implantation. One sheep had an additional
      valve implant because one overdilated stent had become insufficient. Early
      evaluation of the implanted valve function confirmed the perfect competence of 9
      out of 10 valved stents. However, for unknown reasons all the animals died within
      24 hours after the procedure. CONCLUSIONS: Percutaneously implanted valves in the
      thoracic aorta of sheep with massive aortic insufficiency function well in the
      acute study. In comparison to previous surgical results, this technique might
      become an alternative to surgery in patients with chronic aortic insufficiency in
      whom perioperative risks are high.

PMID- 11951057
TI  - Serodiagnostic and immunoprophylactic potential of a 78kDa protein of Leishmania
      donovani of Indian origin.
AB  - BACKGROUND: The serodiagnosis of visceral leishmaniasis due to Leishmania
      donovani using crude parasite antigen is complicated in many endemic areas by
      cross-reactions with serum from humans infected with other protozoan diseases.
      The search for pure antigens avoiding such cross-reactions is in progress.
      Developing a vaccine against cutaneous leishmaniasis has been much more
      successful than against visceral leishmaniasis. Immunoprophylactic studies using
      various combinations of antigens and adjuvants are also in progress, and several
      strategies are in use, with varying degrees of success. MATERIAL/METHODS:
      Promastigotes of Leishmania donovani were used. The 78kDa protein was purified by
      a monoclonal antibody tagged CNBr sepharose CL-4B column. The presence of the
      protein in both stages of the parasite and in kala-azar patient serum was
      analyzed by western blotting. ELISA was used for serodiagnosis and isotype
      analysis of antibodies produced in immunized mice. Immunoprophylactic studies
      were carried out based on in vitro transformation of amastigotes to
      promastigotes. RESULTS: The 78 kDa membrane protein, present in both amastigote
      and promastigote forms of the parasite, was purified to homogeneity. The protein
      was found to have serodiagnostic potential to detect kala-azar. BALB/c mice
      immunized with 78kDa protein revealed reduction in spleen parasitemia. Isotype
      profiles of antibodies produced by immunized mice showed increased production of
      IgG2a and decreased IgG1 levels. CONCLUSIONS: Our results demonstrated, for the
      first time, the serodiagnostic and immunoprophylactic use of a pure membrane
      protein isolated from Leishmania donovani of Indian origin.

PMID- 11951058
TI  - Functional maps of the junctions between interglobular contacts and active sites
      in glycolytic enzymes -- a comparative analysis of the biochemical and structural
      data.
AB  - BACKGROUND: Oligomers and separate subunits of the glycolytic enzymes often have
      different catalytic properties. However, spectral data show an apparent lack of
      significant conformational changes during oligomerization. Since the conformation
      of an enzyme determines its catalytic properties, the structural mechanism(s)
      influencing the activity is of considerable interest. MATERIAL/METHODS: Analysis
      of the spatial structures of the junctions between interglobular contacts and
      binding sites may give a clue to the mechanism(s) of the activation. In this
      work, the problem was studied using available structural and biochemical data for
      the oligomeric enzymes of glycolysis. RESULTS: Computational analysis of the
      structures of the junctions has identified three structurally distinct types of
      junctions: 1. interglobular binding site (2 of 8 enzymes); 2. domain-domain
      stabilization (5 of 8); and 3. 'sequence overlap' or a local conformational
      change (all enzymes). Thus the catalytic activity may be influenced through the
      shifts of the modules of protein structure (types 1, 2) and/or due to a slight
      change in the local structure (type 3). The more common junctions of types 2 and
      3 are well conserved among eukaryotic enzymes, which suggests their biological
      importance. CONCLUSIONS: The results suggest that a profound and a complex change
      in conformation in subunits of an oligomeric enzyme may not be necessary for a
      significant change in the catalytic properties. The analysis maps the residues
      important for the junctions and thus for the link between the catalytic activity
      and the oligomeric state of the enzymes.

PMID- 11951059
TI  - Intracerebroventricular administration of bacterial lipopolysaccharide prevents
      the development of acute experimental pancreatitis in the rat.
AB  - BACKGROUND: Lipopolysaccharides (LPS) are responsible for septic shock but low
      doses of LPS reduce pancreatic damage produced by caerulein-induced pancreatitis
      (CIP) in rats. Leptin, produced by adipocytes attenuates the severity of CIP. The
      aim of this study was to evaluate the effect of intracerebroventricular (i.c.v.)
      administration of LPS on CIP and plasma leptin level and to investigate the
      involvement of sensory nerves (SN) in the effects of LPS on CIP.
      MATERIAL/METHODS: CIP was produced by subcutaneous (s.c.) infusion of caerulein
      (25 Kg/kg) to conscious rats. SN were deactivated with capsaicin (100 mg/kg
      s.c.). LPS (0.2, 2, or 20 Kg/rat) were applied to the right cerebral ventricle 30
      min prior to CIP. RESULTS: CIP was manifested by an increase in plasma levels of
      amylase, lipase, leptin and an anti-inflammatory interleukin 10 (IL-10), (by
      400%, 1000%, 700% and 50%, respectively), confirmed by histological examination
      and accompanied by 40% reduction in pancreatic blood flow. Pretreatment of CIP
      rats with i.c.v. LPS resulted in significant reduction of CIP accompanied by dose
      dependent increase in plasma levels of leptin and IL-10. Deactivation of SN,
      which by itself failed to affect CIP, completely reversed the beneficial effects
      of i.c.v. administration of LPS on CIP and reduced plasma leptin and IL-10
      concentrations. CONCLUSIONS: Pretreatment with LPS given i.c.v. prevents the
      development of caerulein-induced pancreatitis through the activation of SN and
      though the release of leptin.

PMID- 11951060
TI  - Fibrinogen and smooth muscle cell detection in atherosclerotic plaques from
      stable and unstable angina -- an immunohistochemical study.
AB  - BACKGROUND: This study presents a systematic analysis of atherothrombotic lesions
      taken by percutaneous atherectomy and post mortem examination from coronary
      arteries, in order to identify: a) the topographic occurrence of fibrinogen and
      smooth muscle cells (SMCs), b) their independent expression in stable and
      unstable plaques, and c) their co-expression, which can provide a better
      understanding of the involvement of fibrinogen and SMCs in the development and
      progression of atherosclerotic plaques. MATERIAL/METHODS: 120 specimens from
      atherosclerotic lesions were collected, using directional coronary atherectomy;
      40 additional specimens were collected from postmortem examinations. All
      specimens were stained by immunohistochemical methods with monoclonal and
      polyclonal antibodies (DAKO) for fibrinogen and SMCs. RESULTS: Fibrinogen
      appeared to be a component of all stable and unstable coronary atherosclerotic
      plaques, with a significant predominance in unstable angina. No significant
      difference was observed between SMC-stained areas in stable and unstable angina;
      however, a significant difference exists in co-expression of SMCs and fibrinogen
      between unstable and stable angina. Interestingly, the total number of SMCs at
      the first stages of formation of unstable plaques is less than in stable plaques.
      However, in a number of advanced coronary atherosclerotic plaques associated with
      unstable angina, we observed an increasingly progressive inflammatory cell
      activity, in which SMC areas were significantly increased. CONCLUSIONS: This
      distribution of fibrinogen and SMCs suggests the possibility of a link between
      SMC migration and proliferation, intensifying the increased fibrinogen
      concentration in atherosclerotic plaques.

PMID- 11951061
TI  - Effects of acute hypoxemia/ischemia on EEG and evoked responses at normothermia
      and hypothermia in humans.
AB  - BACKGROUND: Hypothermia is used clinically to prevent neurologic injury but the
      degree of protection which it affords at various levels of the nervous system in
      humans is difficult to establish. MATERIAL/METHODS: The temporal changes in EEG
      amplitude and somatosensory evoked potential (SEP) amplitudes in a patient
      experiencing acute normothermic hypoxemia, a patient experiencing acute
      circulatory arrest at moderate hypothermia and a collection of patients
      undergoing deep hypothermic circulatory arrest were analyzed to determine the
      rate at which changes occur during acute lack of oxygen delivery at various
      temperatures. RESULTS: In each case, it was found that more rostrally generated
      potentials disappeared more quickly than more peripheral potentials. All
      potentials decayed more slowly during acute normothermic hypoxemia than during
      circulatory arrest. During circulatory arrest at 14.4 degrees C, the amplitude of
      the Erb's point, N13 and N18 potentials in the SEP took 5 times longer to drop to
      50% of their value at the onset of ischemia than with circulatory arrest at 30.9
      degrees C. CONCLUSIONS: The longer times to disappearance of the SEP potentials
      during deep hypothermia compared to moderate hypothermia was consistent with the
      predicted 3.5-6.5 fold reduction in metabolic activity at deep hypothermia
      compared to moderate hypothermia. The prolonged time to disappearance of the SEP
      during normothermic hypoxemia demonstrates that even with reduced oxygen delivery
      the continued delivery of metabolic substrate can be critical to neural function.

PMID- 11951063
TI  - Side clamp used during off-pump coronary artery bypass does not increase the risk
      of stroke.
AB  - BACKGROUND: The purpose of this study was to investigate whether the incidence of
      stroke after off-pump AC bypass was lower than that after on-pump AC bypass.
      MATERIAL/METHODS: A prospective study was performed with consecutive patients who
      underwent isolated AC bypass in the Shin-Tokyo Hospital Group between July 1,
      1996 and December 31, 2001 AC bypass was defined as coronary artery bypass
      requiring proximal anastomoses onto the ascending aorta. The patients were
      divided into two groups, depending on the use of cardiopulmonary bypass: on-pump
      and off-pump groups. Perioperative data were prospectively collected and the risk
      factors for postoperative stroke were investigated. RESULTS: Preoperative
      comorbidities were more frequent in the off-pump group. The number of distal
      anastomoses was not significantly different but the number of proximal
      anastomoses was significantly greater in the on-pump group than in the off-pump
      group. The incidence of postoperative stroke was 0.3% in the off-pump group and
      2.0% in the on-pump group. Significant risk factors influencing the occurrence of
      postoperative stroke included: use of cardiopulmonary bypass, age over 75,
      peripheral vascular disease, saphenous vein use, and postoperative atrial
      fibrillation. Multivariate analysis demonstrated that the use of cardiopulmonary
      bypass, age over 75, and peripheral vascular disease were isolated predictors of
      postoperative stroke. CONCLUSIONS: The incidence of postoperative stroke was
      lower in the off-pump group than in the on-pump group, even though the side clamp
      was applied to the ascending aorta for aortocoronary bypass. The use of side
      clamping for off-pump AC bypass does not increase the risk of postoperative
      stroke.

PMID- 11951062
TI  - Protocol for rapid sequence intubation in pediatric patients -- a four-year
      study.
AB  - BACKGROUND: To evaluate a protocol for rapid sequence intubation (RSI) for
      pediatric patients in a Level 1 trauma center. MATERIAL/METHODS: Retrospective
      review of prospectively gathered Continuing Quality Improvement (CQI) data at an
      inner city Level 1 trauma center with an emergency medicine residency program.
      Protocols for RSI were established prior to initiating the study. All pediatric
      intubations at the center from February 1996 to February 2000 were included.
      Statistical analysis included descriptive statistics for categorical data and Chi
      square for comparisons between groups. RESULTS: Over the 4-year study period
      there were 83 pediatric intubations ranging in age from 18 months to 17 years;
      mean age 8.6. All had data collected at the time of intubation. There were 20
      (24%) females and 62 (76%) males (p<0.001). Reasons for intubation were related
      to trauma in 71 (86%) and medical reasons in 12 (14%) (p<0.001). Of the trauma
      intubations 7 (10%) were for gunshot wounds, 39 (55%) were secondary to MVCs, and
      the remainder (25; 35%) were from assaults, falls, and closed head injuries. The
      non-trauma intubations were for smoke inhalation, overdose, seizure, HIV related
      complications, eclampsia, and near drowning. Intubations were successful with one
      attempt in 65 (78%) cases. No surgical airways were necessary. Rocuronium was
      used in 4 cases. Protocol deviations did not lead to complications. CONCLUSIONS:
      This protocol based pediatric rapid sequence intubation method worked well in an
      EM residency program. More intubations were in males and more were necessary due
      to trauma in this group.

PMID- 11951064
TI  - Predictors of mortality among nursing home residents with a diagnosis of
      Parkinson's disease.
AB  - BACKGROUND: Little is known about predictors of mortality among Parkinson
      patients living in long term care. MATERIAL/METHODS: We conducted a 3-year follow
      up study on 15,237 PD residents aged 65 years and older using the Systematic
      Assessment in Geriatric drug use via Epidemiology (SAGE) database. The SAGE
      database consists of the Minimum Data Set (MDS) data collected on over 400,000
      nursing home residents in 5 U. S. states, including demographic characteristics,
      dementia severity, comorbidity and other clinical variables. Information on death
      was derived through linkage to Medicare files. Baseline characteristics were used
      to predict survival using univariate and multivariate Cox proportional hazard
      models. RESULTS: The overall 3-year mortality rate was 50%. Advanced age
      (relative rate (RR) 2.22; 95% confidence interval (CI) 1.99-2.47, for patients
      85+ years), male gender (RR 1.73; 95% CI 1.60-1.87), severe functional (RR 1.81;
      95% CI 1.53-2.13) and cognitive (RR 1.54; 95% CI 1.38-1.72) impairment, the
      presence of vision problems (RR 1.25; 95% CI 1.20-1.57), pressure ulcers (RR
      1.25; 95% 1.14-1.37), and a diagnosis of congestive heart failure (RR 1.49; 95%
      CI 1.35-1.65), diabetes mellitus (RR 1.22; 95% 1.11-1.35) and pneumonia (RR 1.39;
      95% CI 1.09-1.77) were independent predictors of death. The specific presence of
      aspiration pneumonia had the highest mortality risk ratio among all comorbidities
      (RR 1.58; CI 0.97-2.56). African-Americans and other minority groups were less
      likely to die relative to white PD residents. CONCLUSIONS: Age, sex, functional
      and cognitive impairment and the diagnosis of pneumonia or congestive heart
      failure were the strongest predictors of death. Minority groups have a reduced
      risk of death relative to white PD nursing home residents.

PMID- 11951065
TI  - Causes for early reintervention after thyroidectomy.
AB  - BACKGROUND: The purpose of our study was to ascertain the causes for early
      reintervention after thyroidectomy performed by a surgical team using a
      systematized surgical technique. MATERIAL/METHODS: We analyzed 1131 patients, 939
      (83.1%) women and 192 (16.9%) men, average age 38.7 years (range 12 to 79). Of
      these patients, there were 675 hemithyroidectomies with isthmusectomy (59.74%),
      189 subtotal thyroidectomies (16.71%), and 267 total thyroidectomies, alone or
      with regional lymphatic dissection at levels VI and VII (23.55%). Statistical
      analysis was performed by main tendency measures and chi square (chi-squared) for
      comparison of two independent samples; the dependent variable was the rate of
      early reintervention, while the independent variables included causes, time of
      presentation, hormonal functional state and extent of surgery. RESULTS: Early
      reintervention was necessary in 11 cases (0.97%). 9 were due to hematoma (0.79%)
      resolved with drainage and hemostasis, and two (0.18%) due to acute respiratory
      failure (ARF) caused by laryngeal edema, resolved by tracheostomy. Analysis based
      on diagnosis, extent of surgery and functional state failed to reveal
      statistically significant differences. The maximum time presentation of
      complications was 6 hours. CONCLUSIONS: The most intense postoperative monitoring
      is necessary during the first six hours. The low frequency of early
      reintervention and the appearance of complications in less than 8 hours enable
      thyroid surgery to be performed on a short-stay basis with adequate safety
      margins.

PMID- 11951066
TI  - Characteristics and outcome among women and men transported by ambulance due to
      symptoms arousing suspicion of acute coronary syndrome.
AB  - BACKGROUND: The purpose of this study was to describe the characteristics and
      outcome in relation to sex in consecutive patients who were transported by an
      ambulance due to symptoms arousing suspicion of acute coronary syndrome.
      MATERIAL/METHODS: Our research involved all patients transported by ambulance
      over a 3-month period in the community of Goteborg due to such symptoms. The P
      values were age adjusted. RESULTS: Of the 930 transported patients fulfilling the
      given criteria, 452 (49%) were of women. The women were older and had a lower
      incidence of previous acute myocardial infarction, angina pectoris, and current
      smoking. Women less frequently had a final diagnosis of acute coronary syndrome
      (22.3% vs 36.6%; p<0.0001) or acute myocardial infarction (10.1% vs 17.9%;
      p<0.0001). However, the mortality rate during one year was the same in women
      (17.2%) and men (18.7%). Women were less frequently clammy on admission to the
      ambulance (17% vs 30%; p<0.0001) and less frequently showed signs of myocardial
      ischemia in ECG upon admission to the emergency department (26% vs 38%; p<0.0001)
      compared to men. Among those patients with an acute coronary syndrome, women more
      frequently complained of dyspnea than men (27% vs 12%; p=0.018). CONCLUSIONS: Our
      study suggests that among ambulance transported patients with suspicion of acute
      coronary syndrome there are some differences between women and men in terms of
      their characteristics and underlying etiology, but not in terms of the risk of
      mortality.

PMID- 11951067
TI  - A multi-center open study to determine the effect of lamivudine on HBV DNA
      clearance and to assess the safety of the regimen in patients with chronic
      hepatitis B infection.
AB  - BACKGROUND: Patients with on-going HBV viral replication often present with
      clinical features of active chronic hepatitis. Until the recent introduction of
      nucleoside analogues, interferon-alpha was the only approved drug for these
      patients. One of the former drugs, lamivudine, has been shown in clinical trials
      in the US and Asia to effectively inhibit the viral polymerase of HBV. Our study
      was undertaken to assess the efficacy and safety of lamivudine therapy in Polish
      patients with chronic hepatitis B. MATERIAL/METHODS: Forty-five patients with
      chronic hepatitis B (HBeAg positive, anti-e negative, HBV-DNA positive by
      hybridization assay) were enrolled in the study. The patients received 100mg of
      lamivudine orally, once daily for 12 months. They returned for routine clinical
      and laboratory control every two weeks during the first months of treatment, and
      later at 3-month intervals while receiving lamivudine. RESULTS: At the end of
      treatment, serum HBeAg was not detected in 21 patients (48.8%), and anti-HBe
      appeared in the serum of 19 patients. 37.2% of the patients in the study group
      showed sustained suppression of serum HBV DNA at the end of treatment. Lamivudine
      therapy was well tolerated, with the rate of occurrence of adverse events similar
      to that observed in other clinical studies. CONCLUSIONS: 12-month lamivudine
      therapy in this Polish population of patients with chronic hepatitis B induced a
      high rate of HBeAg seroconversion, accompanied by reduction of HBV-DNA and the
      normalization of alanine aminotransferase activities.

PMID- 11951068
TI  - Level of antithrombin III, protein C, protein S and other selected parameters of
      coagulation and fibrinolysis in the blood of the patients with recurrent deep
      venous thrombosis.
AB  - BACKGROUND: Thrombophilia is caused mainly by disturbances of hemostasis
      involving excessive coagulation system activation, reduction of anticoagulation
      system (antithrombin III, protein C, protein S, RAPC) or fibrinolytic activity.
      MATERIAL/METHODS: In 34 young patients (aged <40 years) with recurrent deep
      venous thrombosis (>2 incidents) the activity of antithrombin III, protein C, S,
      platelet count, adhesion and aggregation, APTT, stipven-kephalin, prothrombin
      time and INR were investigated. Fibrinogen, factor XIII, ELT, FDP, Ag t-PA
      levels, antigen concentration and PAI-1 activity were determined. Patients with
      idiopathic DVT, after elimination of most important thromboembolism risk factors,
      were qualified for the study. DVT was confirmed in all patients by phlebography,
      plethysmography and ultrasonography. Results were compared with a group of 54
      healthy controls. RESULTS: In almost 50% of patients with recurrent DVT (15/34)
      decrease of at least one plasma coagulation inhibitor (AT III, PC, PS) level was
      observed. In the patient group (with AT III and/or PC and/or PS decrease)
      statistically significant reduction of kaolin-kephalin time in comparison with
      controls was observed (a<0. 01). Analysis of fibrinolysis system demonstrated
      significant factor XIII level decrease (to 58.3%), fibrinogen level increase, ELT
      prolongation, and fibrinogen and fibrin degradation product increase in
      comparison with controls. The patients demonstrated 3-fold higher t-PA antigen
      level (13.1 ng/ml, a<0. 0001) and over 3-fold higher PAI-1 activity (26.7 AU/ml,
      a<0. 001) than healthy controls. CONCLUSIONS: Reduced antithrombin III, protein
      C, protein S activity and excessive activation of the coagulation system with
      secondary fibrinolytic activity increase were found in patients with recurrent
      DVT.

PMID- 11951069
TI  - Assessment of iron metabolism in children with chronic hepatitis B -- prognostic
      factor in interferon alpha therapy.
AB  - BACKGROUND: The aim of the study was to assess iron metabolism in children with
      chronic hepatitis B and to establish whether it had any influence on the results
      of interferon alpha therapy. MATERIAL/METHODS: The study was carried out in a
      group of 38 children aged from 2 to 16 years with chronic hepatitis B diagnosed
      according to serological, biochemical and histopathological criteria. All the
      patients were treated according to the commonly adopted schedule: interferon
      alpha administered subcutaneously three times a week at 3 MIU doses for 20 weeks.
      During the therapy and one-year follow-up after its completion, biochemical liver
      function parameters, serological HBV markers, and iron and ferritin levels were
      monitored. RESULTS: The therapy resulted in obtaining seroconversion in the HBe
      system in 9 patients (23.68%). Liver bioptates in that group of patients
      demonstrated more advanced changes due to inflammatory activity and fibrosis
      processes, significantly higher values of alanine aminotransferase, lower serum
      levels of iron and ferritin with more pronounced difference in ferritin levels,
      although the differences reached no statistical significance. CONCLUSIONS: No
      disturbances of iron metabolism were observed in children with chronic hepatitis
      B. In the group of patients with detectable seroconversion in the Hbe system
      resulting from interferon alpha therapy, lower serum levels of iron and ferritin
      were observed. Routine determinations of serum iron and ferritin levels as a
      prognostic factor for positive response to interferon alpha seem to be of little
      use, especially in children, in whom no iron accumulation in liver tissue is
      observed in histopathological assessment of liver bioptates

PMID- 11951070
TI  - Course of viral hepatitis B and combined B and C hepatitis in children treated
      for neoplastic diseases.
AB  - BACKGROUND: Viral hepatitis C in children is milder than in adults. Patients with
      tumors, because of immune deficits, seem to be at risk of rapid liver disease
      progression. Little is known about the course of HCV and dual HBV-HCV infections
      in such patients. MATERIAL/METHODS: The study assessed clinical courses of HCV
      and dual HBV-HCV infections in 249 children with tumors aged 1-18 years, divided
      into four groups: with HCV infection - 53, HBV-HCV infection - 53, HBV only - 33
      and infection-free - 110. RESULTS: Hepatitis C was often chronic - in 83.3% of
      patients with HCV and 77.3% of those with dual infection. Over 80% had no
      jaundice. Mean AlAT activity was the highest in the HCV group (149.2I202.7 IU/l),
      lower in the dual infection group (123.3I148.1 IU/l; p<0.02), and the lowest in
      HBV (92.7I152.9 IU/l). Transaminasemia course in patients with HCV and dual HBV
      HCV infections was most frequently fluctuating (50.9% and 45.3%, respectively).
      52.8% of children with HCV demonstrated no advanced inflammatory lesions with
      invasion of the lamina limitans, no marked fibrosis, and minimum changes in
      descriptive classification. In 92.3% of children with dual infections,
      inflammatory activity was mild or mean, with no fibrosis in 61.5%, and persistent
      chronic inflammation predominant in descriptive classification (46.1%).
      CONCLUSIONS: HCV and HBV-HCV infections in children with neoplastic diseases tend
      to take chronic forms, but their clinical course is mild with signs of severe
      inflammatory activity or hepatic stroma remodeling observed on histopathology.

PMID- 11951071
TI  - Total IgE levels and skin test results in children under three years of age with
      food hypersensitivity.
AB  - BACKGROUND: The most common tools of allergologic diagnostics are skin prick
      tests (SPT) and total serum IgE (IgE(total)) determinations. MATERIAL/METHODS:
      The study was carried out in a group of 348 children aged 5 to 36 months. All the
      children underwent SPT using 12 food allergens and in 229 of them also 9 inhalant
      allergens were tested. Assessment of test positivity utilized relative criteria,
      i.e. the result was regarded as positive if a wheal with S surface area exceeding
      or equal to 0.25 of the surface area S0 of a control wheal was formed. In this
      study group, 291 had IgE(total) levels determined. They were divided into the
      groups with elevated and normal IgE(total) levels on the basis of two standards,
      i.e. the standards recommended by the manufacturer of the test reagents used to
      determine IgE(total) (BioWhittaker) and the population standards. RESULTS:
      Positive SPT results for food allergens were obtained in 15.8% of the examined
      children, for inhalant ones in 21.8%. The factors taken into account in the
      analysis of impact on SPT results included age, sex, living place and the use
      diet. Elevated IgE(total) levels according to the manufacturer's standards were
      detected in 35.0%, and according to the population standards in 67.0% of the
      examined children. The obtained positive test results were compared with elevated
      IgE(total) in the studied patients. CONCLUSIONS: 1. Feasibility of SPT at this
      age. 2. Determination of normal IgE(total) range in the group of children below
      three requires further studies.

PMID- 11951072
TI  - Salt iodination as a effective method of iodine supplementation.
AB  - BACKGROUND: In January 1997 a new approach to preventing iodine deficiency was
      introduced in Poland. The goal of the present study was to determine whether the
      mandatory iodization of kitchen salt (30 mg KI/kg) has had any impact on ioduria.
      MATERIAL/METHODS: The study was performed on 29 healthy volunteers, aged 22-29
      (average age 23.93 +/- 1.14), examined in 1996 and retested after 36 months of
      iodine supplementation in 1999. Each person underwent a physical examination and
      thyroid ultrasonography. The iodine level was determined using morning urine
      samples. RESULTS: For the duration of the study thyroid volume remained
      unchanged, ranging from 11.48 I3.89 ml in 1996 to 12.11 +/- 3.85 ml in 1998. The
      echostructure was normal in all subjects both in 1996 and in 1999. In 1996 the
      iodine concentration in urine (ICU) in the study group averaged 100.4 +/- 41.5
      mg/L (range from 43.3 to 175.6 microg/L). Seventeen persons had an iodine
      concentration below 100 microg/L. In 1999 the average ICU was 140.7 +/- 78.87
      microg/L. Three subjects had a lower ICU in 1999 (53.93 +/- 24.65 microg/L) than
      in 1996 (104.1 +/- 24.6 microg/L). These persons claimed to have completely
      eliminated the use of added salt in their diet. CONCLUSIONS: We conclude that
      mandatory iodine supplementation method is sufficiently effective when salt is
      used in the diet. In the case of restrictions on salt consumption the use of
      preparations containing iodine should be recommended.

PMID- 11951073
TI  - Drug-induced liver damage -- a three-year study of patients from one
      gastroenterological department.
AB  - BACKGROUND: The aim of our study was to analyze drug-induced liver disease over a
      3-year period in one gastroenterological department. MATERIAL/METHODS:
      International consensus standard definitions and criteria for assessing causality
      of adverse drug reactions were applied to all patients with abnormal hepatic test
      results. RESULTS: Drugs were implicated in hepatic injury in 14 patients (8
      females) in whom causal relationship between drug and liver disease was definite
      or highly probable. The drugs responsible were amoxicillin with clavulanic acid
      (3 cases), fluvastatin and pravastatin (3 cases), antituberculous drugs (2
      cases), estrogens, roxithromycin, asacol, satolol, enalapril and thiamazol. A
      total of 78.6% (11 cases) were classified as hepatocellular or mixed hepatitis,
      while cholestatic injury was found in 21.4% (3 cases). There were no lethal or
      severe (prothrombin < 50%) hepatic drug reactions. In 13 patients the course of
      liver disease after withdrawal of the offensive drug was either acute or
      protracted, while in one patient there was chronic cholestasis (>3 years)
      resulting from injury to interlobular bile ducts by amoxicllin with clavulanic
      acid. CONCLUSIONS: A thorough history of drug intake should be taken in all
      patients presenting with abnormal hepatic test results. Amoxicillin & clavulanic
      acid, cholesterol-lowering and antituberculin drugs were the most frequent
      hepatotoxic factors in our patients. In a majority of cases the liver injury was
      not severe, and resolved after prompt withdrawal of the responsible drug.

PMID- 11951074
TI  - Efficacy and safety of doxofylline compared to theophylline in chronic reversible
      asthma -- a double-blind randomized placebo-controlled multicentre clinical
      trial.
AB  - BACKGROUND: Experimental studies have shown that doxofylline is endowed with a
      remarkable bronchodilator activity with less extra-respiratory effects than
      theophylline. This trial was designed to compare the efficacy and safety of
      doxofylline, theophylline, and placebo in patients with chronic reversible
      bronchial asthma. MATERIAL/METHODS: Three hundred forty-six patients were
      randomly assigned to a 12-week oral treatment with either doxofylline 400 mg
      t.i.d. (high dose), doxofylline 200 mg t.i.d. (low dose), theophylline 250 mg
      t.i.d. (active control) or placebo. Pulmonary function tests (PFTs) were
      performed biweekly. Patients kept records of peak flow meter (PFM) measurements,
      asthma attack rate and beta-2-agonist use (albuterol). RESULTS: Changes in FEV1 2
      hours after the administration of treatments versus baseline exhibited
      statistically significant differences between doxofylline 400 mg t.i.d. and
      placebo and between theophylline and placebo. Similar differences were monitored
      on the other variables (FVC, PFER, FEF(25-75%). Asthma attack rate and use of
      albuterol decreased remarkably with doxofylline 400 mg t.i.d. and theophylline.
      There were few statistically significant differences between doxofylline 200 mg
      t.i.d. and placebo. Significantly more patients had to interrupt treatment
      because of adverse events under theophylline than under doxofylline 400 mg t.i.d.
      (p=0.001). With doxofylline 400 mg t.i.d., the number of patients treated to
      spare one drop-out due to theophylline was 5. CONCLUSIONS: This study provides
      evidence that doxofylline 400 mg t.i.d. is an effective treatment for relieving
      airway obstruction and displays a better safety profile with respect to
      theophylline 250 mg t.i.d. with a favorable risk-to-benefit ratio.

PMID- 11951075
TI  - Comorbid disease profiles of adults with end-stage hip osteoarthritis.
AB  - BACKGROUND: Although hip osteoarthritis is a common disabling condition, an
      incomplete understanding of all factors that contribute to hip osteoarthritis
      disability persists. The objective of the study was to improve our understanding
      of potentially preventable factors that might influence hip osteoarthritis
      disability by examining the prevalence and impact of selected comorbid factors
      potentially associated with the progression and severity of hip joint
      osteoarthritis among patients with end-stage hip osteoarthritis.
      MATERIAL/METHODS: The medical records of 1,000 hip osteoarthritis surgical
      patients were assessed to specifically identify the presence or absence of
      comorbid conditions of the cardiac, vascular or respiratory systems. The
      association between the patient's functional status before and after surgery, and
      the presence or absence of these comorbid conditions, was assessed. RESULTS: Over
      55% of the sample had at least one comorbid condition, such as hypertension or
      cardiac disease. After controlling for age, trauma, type of surgery and gender
      discrepancies, those with two or more comorbidities were found to have greater
      degrees of functional impairment before surgery, and lower post-operative
      functional status after surgery than those with no co-existent disease (p<0.05).
      CONCLUSIONS: Patients with end-stage hip osteoarthritis exhibit a high prevalence
      of vascular-related comorbidities. The disability of patients with hip
      osteoarthritis is increased in the presence of two or more related comorbid
      conditions. These findings suggest a novel focus for primary, secondary and
      tertiary preventive strategies.

PMID- 11951077
TI  - Non-valvular isolated pulmonary artery vegetations.
AB  - BACKGROUND: One of the serious potential complications of complex congenital
      heart defect (CHD) is bacterial endocarditis. Right sided endocarditis accounts
      for 5-10% of all cases of infective endocarditis, with the tricuspid valve more
      frequently affected than the pulmonary valve. Pulmonary artery involvement in
      bacterial endocarditis is very rare, but when it exists it is almost always
      associated with endocarditis of the pulmonary valve: isolated pulmonary artery
      vegetations have not previously been reported before. CASE REPORT: A 6-year-old
      boy with atrial septal defect (ASD), ventricular septal defect (VSD), coarctation
      of the aorta (CA), persistent ductus arteriosus (PDA) and pulmonary hypertension,
      who had been operated for closure of PDA, correction of CA and pulmonary artery
      banding, was readmitted with bacterial endocarditis. In surgery, the VSD was
      closed with a Dacron patch using interrupted pledget buttressed sutures, and the
      ASD was closed using primary sutures. After debanding, while pulmonary
      arteriotomy was performed for patch angioplasty, we observed that the entire
      pulmonary artery trunk, right and left pulmonary artery branches, were filled
      with a solid mass, which was successfully treated by surgical excision.
      CONCLUSIONS: With ongoing improvements in diagnostic tools, especially in
      echocardiography, antibiotic therapy and surgery, CHD can now be treated
      successfully in early infancy or childhood.

PMID- 11951076
TI  - Rehabilitation outcome in a patient awakened from prolonged coma.
AB  - BACKGROUND: This article describes the rehabilitation of a patient recovering
      from a prolonged coma (defined as lasting longer than 4 weeks). The case is
      noteworthy because it exemplifies the possibilities and difficulties entailed in
      treating these patients, who are often regarded as too severely impaired to
      justify intensive rehabilitation efforts. CASE REPORT: The patient is a 28-year
      old Polish male, unmarried, who suffered serious closed head injuries in an
      automobile accident in April of 1999. He was in a comatose state for more than
      two months, with a GCS score of 5. When admitted for rehabilitation he was
      bedridden, with global aphasia, agraphia, limb apraxia, and executive
      dysfunction. The rehabilitation program developed for him is described in detail.
      RESULTS: Over the course of rehabilitation, which began in December 1999 and
      continues to this writing, the patient has regained locomotion capabilities
      (though with impairments), and his speech has improved considerably. The apraxia
      has largely resolved, and he is able to write his name and copy words. He is now
      capable of performing many activities of daily living. CONCLUSIONS: A
      comprehensive program of rehabilitation characterized by a strategic, heuristic
      approach is capable of achieving a good outcome even in very difficult cases,
      such as prolonged coma.

PMID- 11951078
TI  - Dynamic magnetic resonance imaging in soft tissue tumors -- assessment of the
      diagnostic value of tumor enhancement rate indices.
AB  - BACKGROUND: Dynamic MRI is routinely used in the diagnosis of soft tissue tumors
      to supplement static imaging. The aim of our study was to assess the diagnostic
      value of dynamic MRI using the coefficient of total tumor enhancement expressed
      as per cent (tec%) and the tumor enhancement rate coefficient expressed as per
      cent per minute (erc%/min), and to make a comparative analysis of the sensitivity
      and specificity of both parameters. MATERIAL/METHODS: The material consisted of
      45 patients (30 sarcomas, 15 non-malignant lesions). The age of the patients was
      16-64 years. The MRI was done using an Elscint 2T unit, applying gradient echo
      techniques. The coefficient of total contrast enhancement (tec%) and the tissue
      enhancement rate (erc%/min) were calculated. The limit values were determined for
      dividing the tumors into sarcomas and non-malignant lesions. The sensitivity and
      specificity of MRI were calculated and compared using both indices. RESULTS:
      Dynamic MRI with calculation of erc%/min and tec% makes it possible to
      differentiate between sarcomas and non-malignant lesions. CONCLUSIONS: The
      erc%/min was a more sensitive than tec% differentiating parameter in the
      diagnosis of soft tissue tumors.

PMID- 11951079
TI  - Combination of pamidronate and thalidomide in the therapy of treatment-resistant
      multiple myeloma.
AB  - BACKGROUND: Bisphosphonates inhibit the activity of osteoclasts and demonstrate
      antitumor effect, involving induction of plasmocyte apoptosis, blocking of
      angiogenesis, stimulation of Tgd lymphocytes and inhibition of
      metalloproteinases. Bisphosphonates combined with thalidomide, a drug possessing
      confirmed anti-myeloma activity, seem to have potential favorable effect in
      patients with treatment-resistant multiple myeloma with advanced osteolytic
      lesions. MATERIAL/METHODS: 13 patients with treatment-resistant multiple myeloma
      with advanced osteolytic lesions received combined pamidronate and thalidomide
      therapy. All the patients underwent detailed clinical and laboratory control once
      a month. Pamidronate was used at 90 mg i.v. dose administered at 4-week
      intervals, and thalidomide at doses escalated from 200 mg/d in the first week to
      400 mg/d after 3 weeks of the therapy. The mean duration of treatment was 12
      weeks with a range of 3 to 36 weeks. RESULTS: 7 patients (53%) receiving
      pamidronate and thalidomide therapy demonstrated good response involving at least
      25% reduction of monoclonal protein levels in comparison with baseline. All these
      patients reported improvement of osteodynia symptoms, and 3 of them - their
      complete regression. 70% patients experienced side effects (dizziness,
      constipation, somnolence, polyneuropathy) due to thalidomide administration
      CONCLUSIONS: Good response to combined pamidronate and thalidomide therapy can be
      expected in at least 50% of patients with treatment-resistant multiple myeloma
      with advanced osteolytic lesions.

PMID- 11951080
TI  - Effect of diazepam and clonazepam on the function of isolated rat platelet and
      neutrophil.
AB  - BACKGROUND: Benzodiazepine binding sites distinct from the GABA-receptor-chloride
      complex in the central nervous system have been recognized in many peripheral
      tissues, but their physiological role remains unexplained. Our study was
      undertaken to examine the effects of diazepam, clonazepam, and PK 11195, a
      peripheral benzodiazepine receptor antagonist, on the functional and biochemical
      responses of platelets and neutrophils stimulated by different physiological
      agonists. MATERIAL/METHODS: The experiments were conducted on isolated washed rat
      platelets activated by arachidonic acid (AA), adenosine 5'-diphosphate (ADP), or
      thrombin and on isolated rat neutrophils activated by a chemotactic peptide,
      formyl methionyl leucyl phenylalanine (fMLP). RESULTS: The results showed that
      neither diazepam nor clonazepam nor PK 11195 alone augmented the response of
      resting platelets or modified neutrophil response, but diazepam and clonazepam in
      a concentration-dependent manner inhibited thrombin, ADP or AA-stimulated
      platelet aggregation and the thrombin-induced increase in free intracellular
      Ca2+. Both drugs also exerted an inhibitory effect on reactive oxygen species
      (ROS) produced by fMLP-stimulated neutrophils. However, diazepam was about 10
      times more effective than clonazepam. PK11195 did not influence platelet and
      neutrophil function stimulated by agonists, but reversed the inhibitory action of
      both benzodiazepines on platelet activation and ROS production. CONCLUSIONS: The
      results indicated that in vitro diazepam, and in a much smaller degree
      clonazepam, may down-regulate platelet activation and release of some
      proinflammatory mediators by stimulated neutrophils. These effects are probably
      exerted by a specific benzodiazepine binding sites.

PMID- 11951081
TI  - A radical approach to cancer.
AB  - Reactive oxygen species are known to be potentially dangerous, but are also
      needed for signal-transduction pathways. Tumor cells have relatively low amounts
      of superoxide dismutase (SOD), which quenches superoxide anion (O2(-*)), and as a
      result of a higher level of aerobic metabolism, higher concentrations of O2(-*) ,
      compared to normal cells. But this may not be true of all tumor cells. Some tumor
      cells have relatively higher amounts of vitamin E, a potent anti-oxidant, and a
      higher level of anaerobic metabolism, resulting in a balance that is tilted more
      towards higher anti-oxidant capacity. In both instances of higher aerobic and
      anaerobic metabolism methods designed to augment free radical generation in tumor
      cells can cause their death. It is suggested that free radicals and lipid
      peroxides suppress the expression of Bcl-2, activate caspases and shorten
      telomere, and thus inducing apoptosis of tumor cells. Ionizing radiation,
      anthracyclines, bleomycin and cytokines produce free radicals and thus are useful
      as anti-cancer agents. But they also produce many side-effects. 2
      methoxyoestradiol and polyunsaturated fatty acids (PUFAs) inhibit SODs and cause
      an increase of O2(-*) in tumor cells leading to their death. In addition, PUFAs
      (especially gamma-linolenic acid), 2-methoxyoestradiol and thalidomide may
      possess anti-angiogenic activity. This suggests that free radicals can suppress
      angiogenesis. Limited clinical studies done with gamma-linolenic acid showed that
      it can regress human brain gliomas without any significant side-effects. Thus,
      PUFAs, thalidomide and 2-methoxyoestradiol or their derivatives may offer a new
      radical approach to the treatment of cancer.

PMID- 11951082
TI  - Comparison of ultraviolet induced photo-kinetics for lens-derived and recombinant
      beta-crystallins.
AB  - PURPOSE: The photobiology of purified recombinant crystallins has not been
      studied. Here we examine photo-induced aggregation of purified recombinant mouse
      betaA3-crystallin (rbetaA3) and compare it with that of betaL-crystallins
      isolated from bovine lenses. METHODS: rbetaA3-Crystallin was expressed in
      baculovirus-infected Sf9 cells and purified by ion-exchange and gel-filtration
      chromatography. Protein solutions (pH 7.4) were irradiated at room temperature
      using a 308 nm excimer laser and light scattering was registered by attenuation
      of an unabsorbed beam of red light (670 nm). RESULTS: Irradiation of bovine alpha
      crystallin, betaL-crystallin, rbetaA3-crystallin and gammaB-crystallin resulted
      in formation of insoluble aggregates with subsequent light scattering. Different
      slopes and threshold energies were observed for light scattering by each of these
      species. Sensitivity to ultraviolet irradiation induced light scattering as
      determined from threshold energies varied, with gamma-crystallins showing the
      greatest sensitivity, the betaL- and rbetaA3-crystallins showing an intermediate
      sensitivity and alpha-crystallins much less sensitive. Low doses (100 J/cm2)
      resulted in irreversible formation of water soluble oligomers but no insoluble
      aggregates as indicated by changes in light transmission. The photo-behavior of
      rbA3 was similar to mixed betaL-crystallin and different from that of alpha- and
      gamma-crystallins. CONCLUSIONS: Ultraviolet induced sensitivity of purified
      recombinant crystallins reflects that of mixed crystallin populations and should
      provide an indication of the pathogenicity of specific crystallin sequence
      changes associated with lens aging and hereditary cataract.

PMID- 11951083
TI  - Cloning and characterization of the canine photoreceptor specific cone-rod
      homeobox (CRX) gene and evaluation as a candidate for early onset photoreceptor
      diseases in the dog.
AB  - PURPOSE: The cone-rod homeobox protein (CRX) is a member of the homeodomain
      containing protein family expressed in the retinal photoreceptors and
      pinealocytes; it is involved in the regulation of the coordinate expression of
      multiple photoreceptor specific genes during retinal development. Mutations in
      the CRX gene are causally associated with retinal degeneration phenotypes in man.
      To clone the full length cDNA, characterize the genomic organization of canine
      CRX, map the gene in a radiation hybrid (RH) panel, and evaluate it as a
      candidate for canine inherited retinal degenerations. METHODS: cDNA
      representational difference analysis (RDA) was done using normal and cone
      degeneration (cd) affected retinas. Exonic primers designed from consensus
      sequences of mammalian CRX cDNA were used to amplify and sequence dog genomic
      DNA. Canine specific primers were used for RH mapping of CRX on the RH3000 cell
      line. Linkage, sequencing and/or mapping the disease locus was used to evaluate
      CRX as a disease associated candidate gene. RESULTS: The gene comprises three
      exons and two introns and codes for a transcript with a 900 bp open reading frame
      (ORF). In agreement with human map data, RH mapping placed canine CRX on the
      proximal end of CFA1, in a region of synteny with HSA19q13-q13.3. Based on RH
      mapping, meiotic linkage or sequencing data, we excluded CRX as the cause of
      canine early onset photoreceptor degenerations affecting Alaskan malamutes (cd),
      collies (rod-cone dysplasia 2, rcd2), American Staffordshire terriers, and
      Tibetan terriers. CONCLUSIONS: Canine CRX has a high level of nucleotide and
      amino acid sequence identity with orthologous sequences reported for other
      species. The gene is excluded from causal association with 4 early onset
      photoreceptor diseases affecting cones (cd) or rods and cones (rcd2, PRA in
      American Staffordshire terriers, and Tibetan terriers).

PMID- 11951084
TI  - Factors influencing alpha-crystallin association with phospholipid vesicles.
AB  - PURPOSE: Lens lipids undergo a number of changes with age, including an overall
      increase in phospholipid acyl chain saturation and a decrease in length. In
      addition, the amount of membrane bound alpha-crystallin increases dramatically
      with age and with the onset of cataract. The aim of this study was to determine
      if a link exists between age and cataract associated changes in lens lipids and
      the changes in alpha-crystallin membrane association. METHODS: Protein-free lipid
      vesicles composed of a wide variety of synthetic and lens-derived lipid vesicles
      were formed by sonication. These vesicles were used with fluorescent native and
      recombinant alpha-crystallin conjugates in vesicle binding assays. Vesicles were
      collected by centrifugation and bound alpha-crystallin was quantified with
      fluorescence intensity measurements. RESULTS: alpha-Crystallin complexes showed
      remarkably similar binding profiles for all lipid vesicles tested, regardless of
      lipid origin, phospholipid head group, acyl chain length or saturation, and
      inclusion of cholesterol. In addition, recombinant alpha-crystallin complexes
      bind to these vesicles in a manner that is essentially indistinguishable from
      that of native human and bovine alpha-crystallins. Unlike alpha-crystallin
      binding to lens membranes containing intrinsic proteins, binding of alpha
      crystallin to protein-free vesicles was very high capacity and unsaturable.
      CONCLUSIONS: We conclude from these data that the binding of alpha-crystallin to
      lens membranes is not lipid-specific. Furthermore, protein post-translational
      changes, such as phosphorylation, do not appear to alter alpha-crystallin binding
      to these vesicles. Given the linearity of the binding curves, we propose that the
      only limiting factor for normal alpha-crystallin membrane binding is available
      surface area on the bilayer. Finally, the present data suggests that increased in
      vivo membrane association of alpha-crystallin is not a result of lipid changes,
      but more likely a result of non-lipid factors such as the accumulation of high
      molecular weight forms of alpha-crystallin.

PMID- 11951085
TI  - Cis-regulatory elements of the mouse Krt1.12 gene.
AB  - PURPOSE: Keratin 12 is a cornea epithelial cell-specific intermediate filament
      component. To better understand the regulatory mechanism of its expression, the
      cis-regulatory elements located between the transcription start site and 600 bp
      upstream of the Krt1.12 gene were determined. METHODS: The promoter activity of
      reporter gene constructs containing 0.6, 0.4, and 0.2 kb of DNA 5' upstream of
      Krt1.12 coupled to the lac Z gene were determined in rabbit corneas using Gene
      Gun technology. DNA foot printing and EMSA (electrophoresis mobility shift assay)
      were employed to identify putative cis-regulatory elements of the Krt1.12 gene
      using bovine corneal epithelial cell nuclear extracts. RESULTS: Enzyme activity
      assays and histochemical analysis of beta-galactosidase from the 0.6, 0.4, and
      0.2 kb K12 promoter constructs indicated that the DNA elements between -0.2 and 
      0.6 kb 5' of the Krt1.12 gene contain cis-regulatory elements for its corneal
      epithelial cell-specific expression. Foot printing and EMSA showed that the
      sequences between -181 to -111 and -256 to -193 upstream of the Krt1.12 gene
      reacted to nuclear proteins isolated from bovine corneal epithelial cells. A
      Genbank search revealed that these two regions were potential binding sites for
      many transcription factors such as AP1, c/EBP, and KLF6. Immunofluorescent
      staining indicated the presence of c-jun and c/EBP transcription factors in the
      nuclei of corneal epithelial cells. CONCLUSIONS: The data is consistent with the
      notion that the -182 to -111 and -256 to -193 fragments 5' of the Krt1.12 gene
      may serve as corneal epithelial cell-specific cis-regulatory elements, and the
      coordinated interactions of various transcription factors are required for cornea
      specific expression of Krt1.12 gene.

PMID- 11951086
TI  - Optimization of RNA isolation from human ocular tissues and analysis of
      prostanoid receptor mRNA expression using RT-PCR.
AB  - PURPOSE: The isolation and analysis of human ocular RNA is problematic due to
      variables such as rapid degradation, tissue composition, and melanin
      contamination. The purpose of this work was to optimize an extraction protocol
      for the isolation of intact total RNA from a variety of diverse human ocular
      tissues and to employ RT-PCR to assess the expression of mRNA coding for all
      eight prostanoid receptors. METHODS: Total RNA was extracted from human iris,
      ciliary body, choroid, and retina using an RNeasy(R) Midi Kit. Total RNA was
      extracted from human cornea, sclera, and optic nerve using Tri-Pure(R) Isolation
      Reagent. 1.0 microgram of total RNA was reverse transcribed into cDNA and
      subsequently amplified by PCR (35 cycles) using primers designed against each of
      the human prostanoid receptor cDNAs. PCR products were analyzed by gel
      electrophoresis and endonuclease digestion. RESULTS: The total yield and quality
      of RNA derived from each tissue varied according to tissue composition and the
      isolation method employed. RT-PCR analysis revealed that each tissue expressed
      all prostanoid receptor mRNAs, however, 50 cycles of PCR was required to
      visualize FP receptor expression in scleral tissue. In all cases, prostanoid
      receptor mRNA expression was significantly lower than in human nonpregnant
      myometrium, which was used as the positive control. CONCLUSIONS: The different
      cellular composition of each ocular tissue ultimately dictated the methodology to
      be employed for the isolation of total RNA. Thus, two extraction protocols were
      optimized for the isolation of intact high quality RNA from a variety of human
      ocular tissues. The identification of all prostanoid receptor mRNAs in a diverse
      set of human ocular tissues suggests potential mechanisms for prostanoid-based
      therapeutics aimed at IOP reduction and stimulates speculation as to additional
      physiological and or pathophysiological roles mediated by prostanoids.

PMID- 11951087
TI  - Effect of protein kinase Cgamma on gap junction disassembly in lens epithelial
      cells and retinal cells in culture.
AB  - PURPOSE: To determine the effects of protein kinase Cgamma (PKCgamma) on
      phosphorylation of Cx43, the gap junction protein of lens epithelial cells, and
      on cell surface assembly/disassembly of Cx43-gap junction complexes. METHODS:
      Association and phosphorylation of Cx43 by PKCgamma was determined using co
      immunoprecipitation and reaction with phosphoserine antisera. Activation of
      PKCgamma was with 200 nM phorbol ester for 30 to 60 min. Effects of specific PKC
      isoforms was determined after overexpression of either PKCalpha or PKCgamma for
      24 h in N/N 1003A rabbit lens epithelial cells or in two retinal cell lines, WERI
      and Y79. Gap junction plaques were counted on the cell surface by immunolabeling
      of Cx43 using confocal microscopy. RESULTS: Co-immunoprecipitation of Cx43 with
      PKCgamma was observed only in cells over expressing PKCgamma and in cells
      activated with phorbol ester. Both overexpression and phorbol ester produced a
      rapid phosphorylation of Cx43 on serine. Cx43 cell surface gap junction plaques
      decreased in cells over expressing PKCgamma and in cells treated with phorbol
      ester. Similar results were observed using the retinal cell lines, WERI and Y79.
      The effect of PKCgamma overexpression was persistent for 7 days but total cell
      Cx43 was not decreased. Overexpression of PKCa resulted in an increase in cell
      surface gap junction plaques. CONCLUSIONS: PKCgamma can be co-immunoprecipitated
      with Cx43 from lens epithelial cells using phorbol ester activation. PKCgamma
      phosphorylates Cx43 on serine and this causes disassembly and loss of gap
      junction Cx43 from the cell surface. Overexpression of PKCgamma confirmed that
      only this PKC isoform caused the loss of cell surface Cx43. Overexpression of
      PKCalpha, the other major lens PKC isoform, caused an increase in cell surface
      Cx43. The presence of PKCgamma and loss of surface Cx43 from two retinal cell
      lines, WERI and Y79, upon phorbol ester activation further suggests that
      activation of PKCgamma may be a common mechanism for control of cell surface
      Cx43.

PMID- 11951088
TI  - Genomic structure and assessment of the retinally expressed RFamide-related
      peptide gene in dominant cystoid macular dystrophy.
AB  - PURPOSE: Computer-assisted sampling of EST data contained within the UniGene
      human sequences collection is being used to establish a catalog of novel genes
      that are expressed exclusively or predominantly in the human retina. This
      provides a valuable source for candidate genes possibly involved in retinal
      degeneration. In this report we present the characterization of the C7orf9 gene
      locus encoding RFamide-related peptides (RFRPs) and its evaluation in dominant
      cystoid macular dystrophy (CYMD). METHODS: Bioinformatics and cDNA library
      screening were used to isolate the full-length cDNA sequence and to determine the
      genomic organization of C7orf9. Expression profiling was done by RT-PCR and
      Northern blot analysis. C7orf9 was evaluated as a candidate gene for CYMD by DNA
      sequencing and Southern blot analysis in two affected individuals from an
      extended Dutch CYMD family. RESULTS: The C7orf9 cDNA transcript consists of 1190
      bp and is organized into 3 exons on the short arm of chromosome 7 within the
      critical region for CYMD. The transcript is specifically expressed in the retina
      but not in a large range of other human tissues. No disease-causing mutations or
      larger gene rearrangements were found. CONCLUSIONS: We provide the genomic
      organization of the RFamide-related peptide gene, C7orf9, which encodes a
      precursor protein for at least two small neuropeptides, referred to as NPSF
      (alias RFRP-1) and NPVF (alias RFRP-3) and show that it is abundantly expressed
      in the human retina. Results of our comprehensive mutation analysis suggests that
      C7orf9 is not the CYMD gene.

PMID- 11951089
TI  - Acute lymphoblastic leukemia.
AB  - Acute leukemia is the most common childhood malignancy, representing 30% of all
      cancer in American children under the age of 15 years and 12% of cancer cases in
      those ages 15 to 19 years old. In the United States, approximately 2500 new cases
      are diagnosed annually; 80% of these are acute lymphoblastic leukemia, 15% are
      acute myelogenous leukemia, and 5% belong to the chronic leukemia category.(1)
      The survival rates of children with acute leukemia have increased dramatically in
      the last 40 years.(2-5) The most success in outcome has occurred in acute
      lymphoblastic leukemia, although improvement is also being reported in acute
      myelogenous leukemia in the past few years. Progress comes from treatment
      strategy modifications on the basis of observations made in sequential large
      scale therapeutic trials, an approach that serves as a paradigm for research in
      other malignant diseases.

PMID- 11951090
TI  - Acute myelogenous leukemia.

PMID- 11951092
TI  - Par-1 regulates stability of the posterior determinant Oskar by phosphorylation.
AB  - Par-1 kinase is critical for polarization of the Drosophila melanogaster oocyte
      and the one-cell Caenorhabditis elegans embryo. Although Par-1 localizes
      specifically to the posterior pole in both cells, neither its targets nor its
      function at the posterior pole have been elucidated. Here we show that Drosophila
      Par-1 phosphorylates the posterior determinant Oskar (Osk) and demonstrate
      genetically that Par-1 is required for accumulation of Osk protein. We show in
      cell-free extracts that Osk protein is intrinsically unstable and that it is
      stabilized after phosphorylation by Par-1. Our data indicate that posteriorly
      localized Par-1 regulates posterior patterning by stabilizing Osk.

PMID- 11951093
TI  - A distinct class of endosome mediates clathrin-independent endocytosis to the
      Golgi complex.
AB  - Mammalian cells endocytose a variety of proteins and lipids without utilising
      clathrin-coated pits. Detailed molecular mechanisms for clathrin-independent
      endocytosis are unclear. Several markers for this process, including
      glycosphingolipid-binding bacterial toxin subunits such as cholera toxin B
      subunit (CTxB), and glycosyl-phosphatidyl-inositol (GPI)-anchored proteins, are
      found in detergent-resistant membrane fractions (DRMs), or 'lipid rafts'. The
      Golgi complex constitutes one principal intracellular destination for these
      markers. Uptake of both CTxB and GPI-anchored proteins may involve caveolae,
      small invaginations in the plasma membrane (PM). However, the identity of
      intermediate organelles involved in PM to Golgi trafficking, as well as the
      function of caveolins, defining protein components of caveolae, are unclear. This
      paper shows that molecules which partition into DRMs and are endocytosed in a
      clathrin-independent fashion, accumulate in a discrete population of endosomes en
      route to the Golgi complex. These endosomes are devoid of markers for classical
      early and recycling endosomes, but do contain caveolin-1. Caveolin-1-positive
      endosomes are sites for the sorting of caveolin-1 away from Golgi-bound cargoes,
      although caveolin-1 itself is unlikely to have a direct function in PM to Golgi
      transport.

PMID- 11951094
TI  - Effect of cilostazol in patients with intermittent claudication: a randomized,
      double-blind, placebo-controlled study.
AB  - A multicenter, double-blind, randomized, placebo-controlled, parallel study was
      conducted to compare the efficacy and safety of cilostazol 100 mg and 50 mg, both
      administered twice daily, with that of placebo in patients with moderately severe
      intermittent claudication (IC) secondary to peripheral arterial disease.A total
      of 394 subjects 40 years of age or older with chronic, stable, symptomatic IC
      received cilostazol 100 mg twice daily, 50 mg twice daily, or placebo for 24
      weeks. Subjects receiving cilostazol 100 mg twice daily experienced a 21% net
      improvement in maximal walking distance (MWD)compared with placebo subjects (p =
      0.0003) and a 22% net improvement in distance walked to the onset of symptoms
      (PFWD) (p = 0.0015). Subjects who received cilostazol 50 mg twice daily also
      benefited from therapy, but not to a statistically significant degree (7% and 11%
      improvement in MWD and PFWD, respectively). Quality-of-life and functional status
      assessments corroborated these objective results. Cilostazol, in particular 100
      mg twice daily, significantly improves symptoms in patients with IC.

PMID- 11951095
TI  - Intraoperative graft verification in renal transplants.
AB  - The success of an arterial reconstruction is dependent on multiple factors,
      including patient selection, quality of the vessels, type of vascular conduit
      employed, and the surgical technique adopted. Transit time flow measurement is a
      technique that is now the standard of care for immediate graft patency
      verification following coronary artery bypass graft surgery. This study
      demonstrates that transit time flow measurement can be successfully used to
      evaluate renal transplant anastomoses: accurate intraoperative measurements
      provide a rapid objective assessment of renal graft patency.

PMID- 11951096
TI  - Endoluminal graft repair of abdominal aortic aneurysms by vascular surgeons at a
      nonclinical trial center.
AB  - The purpose of this study was to compare the early results and complication rates
      of commercially available endoluminal grafts (ELG) for abdominal aortic aneurysm
      (AAA) by a team of vascular surgeons at a nontrial center with those of published
      results from trial centers. A retrospective chart review of all patients
      undergoing endoluminal graft repair of AAA was made at the medical center. From
      October 1, 1999, to December 31, 2000, a team of vascular surgeons electively
      repaired AAAs in 100 patients at a regional referral center. Of these patients,
      49 underwent repair with a commercially available ELG (35 AneuRx, 14 Ancure)
      whereas the remaining were repaired with an open operation. In the ELG group, the
      primary technical success rate was 100% with a 30-day mortality rate of 2.0%. The
      average hospital length of stay was 3.28 days with ICU stay of 1.20 days. The
      average operative estimated blood loss was 501 mL (100-2,500) with average
      transfusions of 0.49 unit packed red blood cells (prbc) (0-6). Eighty-eight
      percent of ELG patients left the hospital without complication. Seven patients
      (14%) required 11 follow-up procedures for complications including endoleak, limb
      or graft thrombosis, graft stenosis, distal embolization, or wound complications.
      Three of 26 patients (11%) with 6-month computed tomography follow-up had
      evidence of endoleak (2 have subsequently undergone lumbar embolization). Only 1
      6-month follow-up patient had shown increased aneurysm size before endoleak
      treatment. A team of board-certified vascular surgeons at a nonclinical trial
      center can safely perform ELG for AAA with results similar to those of published
      series from trial centers.

PMID- 11951097
TI  - Endovascular repair of thoracic aortic aneurysms: a paradigm shift in standard of
      care.
AB  - The standard open surgical treatment of thoracic aortic aneurysms is associated
      with significant morbidity and mortality. Endovascular repair is less invasive
      and potentially less morbid for patients with multiple risk factors. The authors
      report their results in 9 consecutive high-risk patients treated with
      endovascular grafts from January 1998 through June 2000. There were 7 men and 2
      women patients with an average age of 75 years. Mean aneurysm diameter was 7.1
      cm. All aneurysms were repaired with Gianturco Z-stent polytetrafluoroethylene
      prostheses. There were no perioperative deaths. Mean length of stay was 6.3 days.
      Technical success was achieved in all 9 patients. Two patients had neurologic
      complications following repair (1 patient with transient lower extremity numbness
      related to spinal arthritis and 1 patient with bowel and bladder incontinence).
      Both patients were independent with ambulation. Mean follow-up was 15.8 months.
      There was no evidence of endoleak or stent migration during the follow-up period.
      These findings support endovascular treatment of high-risk patients with thoracic
      aneurysm.

PMID- 11951098
TI  - Routine early postoperative duplex scanning is unnecessary following
      uncomplicated carotid endarterectomy.
AB  - Although early postoperative duplex scanning has become routine after carotid
      endarterectomy (CEA), it is unclear whether the results of these scans alter
      clinical management. The purpose of this study was to critically examine the
      usefulness of early postoperative duplex scans in evaluating the ipsilateral
      carotid artery (for technical perfection) as well as the contralateral carotid
      artery (for potential velocity changes after improvements in ipsilateral flow).
      Consecutive patients undergoing CEA between January 1995 and June 1999 in a
      tertiary hospital setting were studied. Patients underwent early postoperative
      duplex scanning according to the discretion of the operating surgeon and the
      availability of the patient. In 212 patients 236 CEAs were performed with
      selective use of patch closure (49%), intraluminal shunting (19%), and
      intraoperative completion imaging studies (14%). Neurologic complications
      included 3 transient ischemic attacks (TIAs) (1.3%), 3 nondisabling strokes
      (1.3%), and 3 disabling strokes (1.3%). There was 1 30-day death from myocardial
      infarction. Patients were followed up for a median of 18 months (range 0-72
      months). Sixty-five percent of patients undergoing uncomplicated CEA (147/227)
      underwent early duplex surveillance within 6 months of operation. Unsuspected
      sonographic abnormalities were discovered in 8 patients (5%), including 7 cases
      of mild internal carotid artery (ICA) stenosis (>50% by velocity criteria) and 1
      case of common carotid artery (CCA) stenosis (intimal flap). None of the patients
      with ICA stenosis developed symptoms or required operation at any time. The CCA
      intimal flap was electively repaired without complication. Postoperative changes
      in velocity in the contralateral ICA were found in 8/48 (17%) cases. There were 3
      cases of increased velocity, upgrading 1 from 0-49% to 50-79% stenosis and
      upgrading 2 from 50-79% to 80-99% stenosis. The latter patients both underwent
      uneventful contralateral CEA. There were 6 cases of decreased velocity, resulting
      in downgrading of stenoses from 50-79% to 0-49% (n=5) or from 80-99% to 50-79%
      (n=1). Only the latter patient underwent contralateral CEA; the remainder have
      been followed up without intervention. Early scanning appeared to offer no
      clinical benefit; survival and neurologic outcome were the same in the 135
      patients scanned within the first 6 months as in the 68 patients whose first
      postoperative scan occurred later (4-year neurologic event rate 0% in both
      groups; patient survival with early duplex 98 +/- 1.5%, without early duplex 96
      +/- 2.6%; = NS). Early ipsilateral duplex abnormalities following CEA are
      infrequent in asymptomatic patients and, even if found, rarely alter management.
      Patients with bilateral stenosis being considered for contralateral CEA should
      undergo repeat duplex scanning after the first operation, because of the
      significant rate (19%) of contralateral velocity changes induced by ipsilateral
      CEA.

PMID- 11951099
TI  - B-mode ultrasound measurement of carotid bifurcation stenoses: is it reliable?
AB  - In the majority of cases, duplex ultrasonography (DU) is the sole imaging study
      necessary before carotid interventions. Duplex-derived internal carotid artery
      (ICA) peak systolic velocity (PSV), ICA end-diastolic velocity (EDV) and
      ICA/common carotid artery (CCA) PSV ratio are the most commonly utilized
      parameters for predicting critical carotid stenoses. However, the role of direct
      B-mode image measurement of maximal ICA narrowing is ill defined. The images and
      records of 192 patients who underwent both arteriography and duplex
      ultrasonography (DU) of 375 carotid arteries from January 1995 to November 2000
      were reviewed. All DUs were performed by registered vascular technologists (n=6).
      Maximum arteriographic stenosis was determined according to the NASCET study
      design. With arteriography as the "gold standard," B-mode image (BMI) measurement
      of the maximal ICA luminal narrowing relative to the carotid bulb (n=162)as well
      as the peak systolic velocity in the internal carotid artery (PSVICA) (n=330),
      end-diastolic velocity in the internal carotid artery (EDV(ICA)) (n=198), and the
      ratio of the PSVs in both the ICA and the CCA (PSVICA/CCA) ratio (n=319) were
      subjected to receiver operator characteristics (ROC) curves for 3 clinically
      relevant stenoses thresholds: 50-99%, 60-99%, and 70-99%. A strong correlation
      was found between B-mode image (BMI)and the NASCET arteriographic measures of
      carotid stenosis (r =0.80;p<0.001) and was similar among the 6 technologists (r
      =0.74-0.89;p>0.2). The overall accuracy of BMI measurement to diagnose 50%,
      60%,and 70% arteriographic carotid stenosis was 85.3%, 82.2%, and 87%,
      respectively. BMI measurement was similar to the most accurate PSV(ICA),
      EDV(ICA), and PSV(ICA/CCA) ratio at all 3 threshold stenoses levels (p>0.3). When
      combined with the velocity criteria, BMI measurement improved the positive
      predictive value (PPV) for all arteriographic stenoses thresholds by an average
      of 12.6% for PSV(ICA), 21.2% for EDV(ICA), and 14.2% for PSV(ICA/CCA) ratio. BMI
      measurement of carotid bifurcation narrowing is as reliable as duplex-derived
      velocity criteria in evaluating clinically relevant threshold ICA stenoses. The
      routine use of B-mode ultrasound in conjunction with the velocity parameters
      enhances the PPV of carotid DU. Our experience suggests that with current
      refinements in B-mode resolution, BMI stenosis measurements are accurate among
      experienced technologists and are a useful adjunct to duplex-derived velocity
      parameters.

PMID- 11951100
TI  - Angiographic access site complications in the era of arterial closure devices.
AB  - Coronary and peripheral angiography is associated with a low but significant risk
      of access site complications. While percutaneous devices have been shown to
      permit more rapid puncture site closure, previous reports have suggested the
      incidence and severity of complications associated with these devices are greater
      than with manual compression. This study compares access site complications with
      and without closure devices in the current era. The authors conducted a
      retrospective review of patients with access site complications after coronary or
      peripheral angiography between 1998 and 2000. Forty-five complications requiring
      vascular surgical consultation were identified in the 4,800 procedures performed
      during this time period. Fourteen complications occurred in 1,536 procedures
      (0.9%) using suture-mediated or collagen devices and 31 occurred in 3,264
      procedures without devices (0.9%). The types of procedures and catheter sizes
      (mean 7 Fr) used were not different in the 2 groups. Other than complications
      involving a retained device, there was no difference between device and manual
      compression with respect to incidence or types of complication,requirement for
      operation, type of operation, or outcome. Access site complications identified
      included pseudoaneurysm (n = 22; 49%), bleeding or hematoma (n = 8;18%),
      arteriovenous fistula (n=5;11%), arterial thrombosis (n = 4;9%), infection (n =
      4;9%), and retained device (n = 2;4%). Twenty-four patients (71% vs 45%; p = NS)
      required operative intervention including pseudoaneurysm repair, hematoma
      drainage, and thrombectomy. Eleven patients (26%) underwent successful ultra
      sound-guided pseudoaneurysm compression and 9 patients (21%) required no
      intervention. These data demonstrate that closure devices facilitate arterial
      puncture site repair without an increase in access site complications. These
      devices can be safely utilized when rapid hemostasis is desired after coronary or
      peripheral angiography.

PMID- 11951101
TI  - Vascular complications arising from maldeployed stents.
AB  - The authors present 6 unusual vascular complications secondary to maldeployed or
      undeployed vascular stents. They retrospectively reviewed patients referred for
      complications of vascular stent placement from September 1998 to March 1999.
      Information on patient history was obtained from a computerized database and
      clinical document file. Radiographic information was obtained from arteriograms,
      ultrasound, and computed tomography imaging. Case 1 describes an undeployed stent
      in the superior mesenteric artery with subsequent thrombosis in addition to
      celiac occlusion secondary to attempted balloon angioplasty. Case 2 refers to a
      malpositioned stent placed in the aortic arch and proximal left common carotid
      artery. Case 3 involves an undeployed coronary stent that migrated to the right
      distal posterior tibial artery, causing vascular occlusion and chronic pain. In
      Case 4, an attempted stent placement into the left iliac artery resulted in an
      undeployed stent lodged across the aortic bifurcation. Case 5 illustrates a
      partially deployed stent occluding the left renal artery that was unamenable to
      further angioplasty. Case 6 demonstrates arterial dissection with a
      pseudoaneurysm following stent placement for right subclavian stenosis. Five
      patients required operative intervention. Increased use of stents may escalate
      the number of complications requiring operative intervention. Foreign bodies can
      migrate distally and potentiate thrombotic occlusion of vessels. Caution must be
      used not only at the time of deployment but also in the follow-up period.
      Continued surveillance becomes important after vascular stent placement.

PMID- 11951102
TI  - Angioplasty with stenting is effective in treating blue toe syndrome.
AB  - Blue toe syndrome is a manifestation of distal embolization associated with
      significant pain and risk of tissue loss. The recommended treatment options for
      this problem include endarterectomy or bypass with exclusion of the source of
      emboli. Although focal arterial stenosis can be effectively treated with
      angioplasty,it is unclear whether performing angioplasty in a lesion suspected of
      causing distal embolization might actually worsen the condition or what long-term
      effects this would have in preventing future embolization. The purpose of this
      study was to evaluate the treatment and outcome of a series of patients with
      unilateral blue toe syndrome treated with percutaneous angioplasty and stenting.
      During a 5-year period, a total of 8 patients were identified with unilateral
      blue toe syndrome. Ankle/brachial indices (ABIs) were obtained, followed by
      arteriography. The study group included 4 men and 4 women with an age range of 35
      to 83 years. Their atherosclerotic risk factors included smoking (8),
      hypertension (5), diabetes mellitus (3), and hypercholesterolemia (1). One
      patient had a history of illicit drug use. The patients were followed up by
      repeat clinical examinations and vascular laboratory studies. Arteriography
      typically demonstrated a focal preocclusive lesion with thrombus at the distal
      end of the lesion. Angioplasty and stent placement was technically successful in
      all cases. The ABIs increased following angioplasty (before 0.81 +/- 0.05; after
      1.02 +/-.05). The symptoms resolved in all 8 patients over the ensuing month, and
      there were no recurrences with a mean follow-up of 18.5 months (range 4 to 36
      months). There was 1 death at 4 months associated with preexisting colon
      carcinoma. Unilateral arterial to arterial emboli were found in association with
      focal preocclusive lesions. Despite the presence of thrombus in some of the
      lesions, these patients were not acutely worse following angioplasty. There was
      good initial angiographic success in all cases. There was also hemodynamic
      improvement as shown by the increased ankle/brachial indices. Although long-term
      follow-up is not available, these intermediate results suggest that angioplasty
      and stenting should be considered a reasonable alternative to standard operative
      approaches for patients with blue to syndrome associated with embolization from a
      focal stenosis.

PMID- 11951103
TI  - Regarding "Vascular Surgeon Edwin J. Wylie, MD (1918-1982), Pioneer and
      Visionary" (Vascular Surgery 35:213 219, 2001).

PMID- 11951104
TI  - [Regulation of inflammatory responses by MAPK signal transduction pathways].
AB  - Mitogen  activated protein kinase (MAPK), which is one of the important signal
      transduction systems in organisms, is involved in many cellular processes, such
      as cell growth, development, division, differentiation, death and coordination of
      cellular functions, and etc. Four subfamilies of MAP kinases, i  e   ERK,
      JNK/SAPK, p38/RK and ERK5/BMK1, have been identified and cloned in mammalian
      cells   These MAP kinases are activated by many proinflammatory stimuli and play
      an important role in the pathogenesis and development of inflammation. In this
      article recent advances in the study of the mechanisms underlying activation of
      MAPKs in infection and inflammation and the molecular basis of specific
      inhibitors for MAPKs are reviewed, in special reference with the perspective
      prevention and treatment of inflammation by these kinases.

PMID- 11951105
TI  - [Signal transduction pathway for antral smooth muscle cell  contraction induced
      by motilin and gastrin in rats].
AB  - Signal transduction pathway that mediates motilin   and gastrin  induced
      contraction of antral smooth muscle cells was investigated in rats. The results
      are as follows. (1) Motilin and gastrin induced contraction of isolated gastric
      smooth muscle cells in a dose  dependent manner. (2) Motilin   and gastrin 
      induced antral smooth muscle cell contraction was inhibited by antibodies against
      G(  i-3). Motilin and gastrin caused an increase of Guanosine  5  -(3-  (35)S 
      thio)triphosphate(  (35)S  GTPgammaS) binding of G(  i-3). (3) Contraction of
      antral muscle cells induced by motilin and gastrin was inhibited by the
      phospholipase C (PLC) inhibitor U  73122 and the IP(3) receptor antagonist
      heparin. The results suggest that motilin  and gastrin  induced contraction of
      rat antral smooth muscle cells is mediated by stimulating G(I) protein coupled
      with PLC that produces IP(3).

PMID- 11951106
TI  - [Isolation of regulation genes related with liver regeneration by  
      representational difference analysis].
AB  - mRNA isolated from 2/3 partially hepatectomied rats was used as a   tester   for
      representational difference analysis (RDA). The subtracted tester cDNA was cloned
      into a T  vector and a rat regeneration liver  specific EST pool was constructed,
      which contained about 30000 independent clones. A sequence analysis of 52 clones
      randomly picked up from this pool indicated that the liver regeneration specific
      sequences were enriched, and the results of RNA blots revealed some novel genes
      in association with liver regeneration.

PMID- 11951107
TI  - [Adenosine inhibits spontaneous and glutamate  induced   discharges of
      hippocampal CA1 neurons].
AB  - Effects of adenosine (Ado) on spontaneous and glutamate induced discharges of
      neurons in CA1 area of hippocampal slices were examined using extracelluar
      recording technique. The results are as follows. (1) In response to the
      application of Ado (0.01 0.1 micromol/L, n=20) into the superfusate, spontaneous
      discharge rates (SDR) of 20 neurons decreased significantly in a dose dependent
      manner. (2) Both Ado non selective receptor antagonist 8 phenyltheophylline (8
      PT, 0.5 mmol/L) and Ado selective A1 receptor antagonist 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX, 50 nmol/L), completely blocked the inhibitory effects of
      Ado in 22 CA1 units. (3) In 10 units, ATP sensitive K(+) channel blocker
      glibenclamide (Gli, 15 mmol/L) also abolished the effect of Ado. (4) Application
      of glutamate (Glu, 0.2 mmol/L) into the superfusate for 2 min led to a marked
      increase in the discharge rate of 15 neurons in an epileptiform pattern; the
      epileptiform discharges induced by glutamate (Glu, 0.2 mmol/L) in 15 neurons were
      suppressed significantly by application of Ado (10 micromol/L) into the
      superfusate. (5) 8-PT (2 mmol/L), DPCPX (200 nmol/L) and Gli (7 mmol/L) were all
      capable of abolishing the inhibiting effect of Ado on the action of glutamate.
      Taken together, it is suggested that Ado can bind with adenosine A1-receptors on
      CA1 neurons, resulting in an activation of K(ATP) channels and inhibition of
      neuronal activity. The inhibitory effect of Ado on glutamate induced epileptiform
      activities in rat hippocampal neurons is also mediated by adenosine A1-receptor
      with involvement of ATP-sensitive potassium channels.

PMID- 11951108
TI  - [Responses induced by dopamine in   Xenopus laevis  oocytes injected with mRNA
      from heat injured rat striatum].
AB  - Poly(A)(+) mRNA isolated from the striatum of normal rats and heat injured rats
      by RNAgents Total RNA Isolation System and PolyTract mRNA RNAgents Isolation
      Systems was microinjected into   Xenopus laevis   oocytes to express functional
      neurotransmitter receptors. Membrane currents were recorded by the conventional
      patch clamp technique for measuring the relative amounts of mRNA encoding
      dopamine receptor in order to study the change in dopamine receptors in heat
      injured rat striatum. There was no change in resting membrane potentials of the
      oocytes before and after mRNA injection. Dopamine induced membrane currents were
      shown to be mediated through Cl(  ). The oocytes injected with mRNA from heat
      injured rat striatum were less sensitive to dopamine than those injected with
      mRNA from normal rats (  P<0.05). The above result showed that heat injury
      affected gene expression and signal transduction of dopamine receptors in rat
      striatum.

PMID- 11951109
TI  - [Relationships between learning and memory and expression of nov gene of rats].
AB  - During the establishment of learning and memory of adult rats with active
      avoidance reaction expression of nov gene, nov mRNA positive neurons and NOV
      protein immunoreactive neurons were found in hippocampus, cingulate cortex,
      globus pallidus, caudate putamen and hypothalamus. The strongest positive
      reaction of NOV protein was observed in high ability group of learning and memory
      (HALM). Basic expression was found in pseudoconditioning (PC) group. The
      expression of NOV protein was higher in low ability group of learning and memory
      (LALM) than in PC group. No significant difference was detected in nov mRNA
      positive reaction between the three groups. The results indicate that nov gene
      may play an important role in learning and memory of adult rats. This regulation
      occurs at the level of NOV protein translation.

PMID- 11951110
TI  - [Protective effect of exogenous glial cell line  derived neurotrophic factor on
      neurons after sciatic nerve injury in rats].
AB  - The aim of the study was to investigate the effect of exogenous glial cell line 
      derived neurotrophic factor (GDNF) on spinal cord neurons after sciatic nerve
      axotomy. Upon silicone  tubulization of transected sciatic nerve in the adult
      rat, either 0.9% saline or GDNF solution was injected into the silicone chamber.
      It was observed by Nissl and enzyme histochemistry staining that exogenous GDNF
      decreased lesion  induced motor neuron death in lateral nucleus of spinal
      anterior horn and the changes in activity of cholinesterase and acid phosphatase
      in spinal cord and sensory ganglions. These results suggest that exogenous GDNF
      is capable of protecting motor neurons from death induced by peripheral nerve
      injury.

PMID- 11951111
TI  - [Inhibition of ERK1/2 activity and   c-fos   mRNA after coronary   artery balloon
      injury by intracoronary radiation in swine].
AB  - The effect of intracoronary radiation on extracellular signal regulated kinase
      1/2 (ERK1/2) activity and c-fos mRNA after coronary artery balloon injury was
      investigated in swine. Twenty three swines were randomly divided into a radiation
      group and a control group after coronary balloon over stretch. The dilated
      segments in the radiation group were exposed to a dose of 20 Gy by a catheter
      based radiation system. The animals were sacrificed at 3 (6 swines from each
      group) and 30 days (6 swines from radiation group and 5 from control group) after
      the operation. The injured segments were processed to examine c-fos gene
      expression by reverse transcription polymerase chain reaction (RT PCR) and to
      measure the activity of ERK1/2 biochemically. Intracoronary radiation decreased
      significantly the ERK1/2 activity and gene expression of c-fos in the radiation
      treated animals 3 days after coronary balloon injury (20.5%,P<0.01;
      47.7%,P<0.05), but neither ERK1/2 activity nor c-fos gene expression was
      significantly affected by endovascular radiation in animals 30 days after balloon
      injury. Therefore, both ERK1/2 and c-fos may be involved in inhibiting
      restenosis.

PMID- 11951112
TI  - [Role of calcineurin in cardiac fibroblast proliferation   stimulated by
      angiotensin II].
AB  - The present study was undertaken to observe the role of calcineurin (CaN) in the
      angiotensin II (Ang II) stimulated cardiac fibroblast proliferation. In cultured
      cardiac fibroblasts of neonatal rats, Ang II was used to stimulate proliferation
      while CaN was inhibited by CaN CsA inhibitor cyclosporin A (CsA). (3)H-TdR
      incorporation, activity of CaN and intracellular calcium concentration were
      measured. (3)H-TdR incorporation of Ang II stimulated fibroblasts was 72% higher
      than control (P<0.01), which was inhibited by CsA (0.1 10 micromol/L) in a dose
      dependent manner. Intracellular Ca(2+) level and CaN activity of Ang II
      stimulated fibroblasts were respectively 112% (P<0.01) and 17%(P<0.05) higher
      than control. It is concluded that CaN may play an important role in signal
      transduction of the Ang II induced cardiac fibroblast proliferation.

PMID- 11951113
TI  - [An analysis of ionic flow of spontaneous slow action potential of guinea pig
      aortic vestibule].
AB  - Spontaneous slow action potentials of aortic vestibule of isolated guinea pig
      heart were intracellularlly recorded. Electrophysiological parameters examined
      are: maximal diastolic potential (MDP), amplitude of action potential (APA),
      maximal rate of depolarization of phase 0 (V(max)), velocity of diastolic
      depolarization of phase 4 (VDD), duration of 50% and 90% repolarization (APD(50)
      and APD(90)) and rate of pacemaker firing (RPF). It was found that (1) 0.5
      micromol/L nisoldipine (Nis) significantly decreased APA, V(max), VDD and RPF
      (P<0.01); (2) 1.2 mmol/L tetrodotoxin (TTX) significantly decreased APA and
      V(max) (P<0.05), but VDD and RPF were significantly slowed down as compared with
      control (P<0.01); (3) 2 mmol/L 4-aminopyridine (4-AP) elicited a decrease in MDP,
      APA and V(max) (P<0.01), but an increase in VDD and RPF (P<0.01); (4) when 1.5
      mmol/L CsCl was perfused for 5 min, the VDD and RPF were significantly decreased
      (P<0.05); and (5) under the condition of hypoxia and perfusion with deprived
      glucose content for 15 min, the VDD and RPF were decreased (P<0.01). The above
      results suggest that (1) in addition to Ca(2+), Na(+) current contributes to
      generation of 0 phase of depolarization of slow response activity in aortic
      vestibule mainly, and (2) in addition to the inward Ca(2+) and Na(+) current and
      attenuated K(+) current, I(f) current also plays some role in phase 4 of
      depolarization.

PMID- 11951114
TI  - Effects of microinjection of adenosine into area postrema on heart rate, blood
      pressure and renal sympathetic nerve activity in rats.
AB  - The effects of microinjection of adenosine (Ado) into area postrema (AP) on mean
      arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity
      (RSNA) were examined in 53 anesthetized Sprague Dawley rats. The results obtained
      are as follows. (1) Following microinjection of Ado (1 ng/60 nl) into AP, MAP, HR
      and RSNA were decreased from 13.76+/-0.46 kPa, 356.28+/-4.25 bpm and 100+/-0% to
      11.23+/-0.49 kPa (P<0.001), 336.91+/-5.23 bpm (P<0.01) and 70.95+/-5.19%
      (P<0.001), respectively; (2) 8-phenyltheophylline (150 microgram/kg, 0.2 ml,iv),
      a nonselective adenosine receptor antagonist, and 8-cyclopentyl-1,3
      dipropylxanthine (500 microgram/kg, 0.2 ml, iv), a selective A(1) adenosine
      receptor antagonist, blocked the inhibitory effect of Ado completely; and (3)
      glibenclamide (5 mg/kg, 0.2 ml, iv), a blocker of ATP-sensitive potassium
      channel, also abolished the effect of Ado. The above results indicate that
      microinjection of Ado into AP induces inhibitory effects on MAP, HR and RSNA,
      which may be related to activation of ATP-sensitive potassium channels mediated
      by A(1) receptors.

PMID- 11951115
TI  - [Effect of protein kinase C on inhibition of nitric oxide synthesis in   cultured
      neonatal rat cardiomyocytes by angiotensin II].
AB  - The purpose of the present study was to investigate the effect of angiotensin II
      (Ang II) on nitric oxide (NO) concentration and its signal transduction pathway
      in cultured neonatal rat cardioymocytes. NO content was measured in cultured
      neonatal rat cardiomyoctes using a nitrite/nitrate colormetric method kit. NO
      content was represented by measured nitrite (NO(2)) and nitrate (NO(3)) level
      (NO(2)/NO(3)). The results are as follows. NO production was decreased by Ang II
      in a dose  dependent manner but increased by L  Arg. The Saralasin, an antagonist
      of Ang II receptor, inhibited the effect of Ang II on NO production. The effect
      of Ang II on NO production was inhibited by NOS blocker N(G)-nitro-L-arginine
      methyl ester   L-NAME   but not by L-Arg. Pretreatment of Phorbol 12-myristate 13
      acetate   PMA  , a PKC activator, decreased NO concentration significantly. This
      effect was strengthened by L-NAME. Staurosporine, a PKC inhibitor, abolished the
      inhibiting effect of Ang II on production of NO. The above results suggest that
      Ang II could decrease NO content in cultured neonatal rat cardiomyocytes
      significantly. Activity of NOS may be inhibited by Ang II. Ang II receptor was
      involved in the inhibitory effect of Ang II on NO production. Activation of
      protein kinase C (PKC) decreased significantly NO production in cultured neonatal
      rat cardiomyoctes, which appears to be associated with PKC in the signal
      transduction pathway.

PMID- 11951116
TI  - [The changes in the heart and erythrocyte L-arginine transport of spontaneously
      hypertensive rats].
AB  - Changes of L-arginine/nitric oxide pathway in heart and of L  arginine transport
      in erythrocytes and their relationship were investigated in spontaneously
      hypertensive rats (SHR). 12 and 16 weeks old SHR, 16 weeks old SHR with captopril
      treatment for 4 weeks and 16 weeks old Wistar-Kyoto (WKY) rats were used. L 
      arginine transport of myocardial ventricular tissue and erythrocytes, total
      nitric oxide synthase (tNOS) activity, nitrite and nitrate (NO(2) + NO(3)) and
      cyclic GMP (cGMP) content in myocardium were measured. The result showed that in
      myocardial ventricular tissue of SHR L-arginine transport decreased significantly
      with V(max) of the high-affinity transport being decreased by 24.3% (P<0.05, 12W
      group), 36.4% (P<0.01, 16W group) as compared with WKY group. Michaelis constant
      (K(m)) of low  affinity transport was significantly lower than that of WKY group.
      NO(2) + NO(3) and cGMP content were respectively decreased by 24.6%, 19.8%
      (P>0.05, P<0.05, 12W group), 52.5%, 60.4% (P<0.05,  P<0.01, 16W group) and 14.8%,
      23% (P>0.05,  P<0.05, SHR+C group) as compared with WKY group. But the K(m) of L
      arginine high-affinity transport and the V(max) of low  affinity transport and
      tNOS activity were not significantly changed. In erythrocytes, the changes of L
      arginine transport coincided with those of myocardial tissue. The V(max) had
      significant positive correlation with the V(max) of high-affinity transport in
      myocardial tissue, r=0.5606, P=0.01 and had negative correlation with left
      ventricular weight to body weight radio, r=0.6231,P<0.01.  These results indicate
      that the activity of L-arginine/nitric oxide pathway inhibited in myocardial
      tissue of SHR. The correlation between the inhibitory degree of L-arginine/nitric
      oxide pathway and the degree of ventricular hypertrophy is negative. The changes
      of L-arginine transport in erythrocytes coincide with those in myocardium.

PMID- 11951117
TI  - [Modulation of prolactin (PRL) secretion in human uterine decidual cells at early
      pregnancy].
AB  - Decidualization is essential for implantation of embryo and maintenance of
      pregnancy in human. The mechanism of decidualization was investigated in this
      study by regulation of prolactin (PRL) release in cultured human decidual cells
      during first trimester of gestation. Progesterone significantly stimulated PRL
      secretion, but the effect of estrogen depended on its concentration, which was
      ineffective at the physiological level (10(  9) mol/L) but suppressed the
      stimulatory effect of progesterone at higher levels. Thus adequate proportion of
      estrogen and progesterone is important for the decidualization. Furthermore,
      RU486 dramatically inhibited PRL release, suggesting that the effect of
      progesterone was mediated, at least in part, through its receptor. cAMP at
      concentration higher than 10(  5) mol/L significantly increased PRL secretion,
      suggesting that the cAMP signal pathway might be involved in decidualization.

PMID- 11951119
TI  - [Alteration of sensitivity of supraoptic nucleus neurons to cytokine in the
      hypothalamic slices from the rat after lipopolysaccharide injection].
AB  - Using the whole  cell patch  clamp technique, the effects of interleukin  1beta
      (IL-1beta) and IL-2 on the membrane potential and spontaneous discharges in the
      supraoptic nucleus (SON) neurons from the rat hypothalamic slices   in vitro  
      were examined to determine the changes in sensitivity of supraoptic nucleus
      neurons to cytokine. The results obtained are as follows. IL-1beta (100 U/ml)
      hyperpolarized the SON neurons from the control rats (n=15) and the rats 9 d
      after i.p. lipopolysaccharide (LPS) (n=20), and decreased the rate of their
      spontaneous discharges. When 100 U/ml IL-2 was perfused, most SON neurons (n=14)
      from the control rats were hyperpolarized and the spontaneous firing decreased,
      but the rest (n=3) remained unchanged. When IL-2 (100 U/ml) was applied, 19
      neurons out of the 45 SON neurons from the rats 9 days after i.p. LPS were
      depolarized accompanied with an increase of the discharges, 16 did not show
      significant changes in both membrane potential and spontaneous discharges, the
      rest 10 were hyperpolarized and their discharges were suppressed. These results
      show that the sensitivity of part of SON neurons from the immuned rat to cytokine
      IL-2 was altered, suggesting that IL-2 may be involved in modulation of the
      activity of SON neurons and thus play a role in modulation of the immune
      response.

PMID- 11951118
TI  - [Effects of microinjection of amino acids into pre-Botzinger complex on
      respiration in adult rats].
AB  - Experiments were performed on sodium pentobarbital anesthetized and bilaterally
      vagotomized adult SD rats. Microinjection of an excitatory neurotoxin, kainic
      acid, into pre-Botzinger complex initially lengthened the duration of
      inspiration, shortened the duration of expiration and increased the respiratory
      frequency, and subsequently abolished rhythmic respiration. Injection of an
      excitatory amino acid, L-glutamate, shortened the duration of expiration.
      Injection of the inhibitory amino acids (either glycine or gamma-aminobutyric
      acid) shortened the duration of inspiration. These results suggest that the pre
      Botzinger complex in adult rats plays an important role in neurogenesis and
      maintenance of rhythmic respiration.

PMID- 11951120
TI  - [Effects of berberine on intracellular calcium concentration in smooth muscle
      cells of guinea pig colon].
AB  - The purpose of the present investigation is to study how berberine (Ber) affect
      the intracellular free calcium concentration ( Ca(2+) (i)) of the smooth muscle
      cells of guinea pig colon by means of biwavelength spectrophotometry with Fura 2
      AM in a cell suspension specimen. In the resting state, Ca(2+) (i) in HEPES
      Ringer solution (CaCl2 1.5 mmol/L) was 108 9.4 nmol/L (n=7), which was not
      significantly affected by Ber. On the other hand, Ber inhibited the increased
      Ca(2+) (i) induced by 60 mmol/L KCl in a dose dependent manner, with a value of
      IC(50) being 34.09 micromol/L. 30, 100 micromol/L Ber also inhibited 10
      micromol/L ACh evoked Ca(2+) (i) elevation in a dose dependent manner either in
      the presence or absence of extracellular Ca(2+). In addition, Ber inhibited
      cyclopiazonic acid (CPA) stimulated Ca(2+) (i) elevation dose dependently. This
      effect was more potent in HEPES Ringer solution (IC(50)=37.79 micromol/L) than in
      Ca(2+) free medium (IC(50)=49.70 micromol/L). The above results suggest that Ber
      exerts an inhibitory effect on the extracellular Ca(2+) influx and the Ca(2+)
      release from intracellular stores.

PMID- 11951121
TI  - [Effects of intracerebroventricular injection of angiotensin II on blood  
      pressure and discharges of habenula nucleus cardiovascular neurons].
AB  - The effects of icv and iontophoretic application of angiotensin II (A II) and
      Sar(1),Thr(8) -A II (ST-A II) on blood pressure (BP) and electroneurogram (ENG)
      of habenula nucleus (Hb) cardiovascular neurons were studied in stress induced
      hypertensive (SIH) and normotensive rats. Increase and decrease of BP could be
      induced respectively by icv of A II (20 microgram) and ST A II (20 microgram), to
      a greater extent in SIH than in the normotensive group. Icv A II also increased
      the ENG of MHb cardiovascular neurons in both the groups, but the increase was
      significantly greater in SIH group than in the normotensive one. Iontophoretic
      application of A II increased the ENG of Hb cardiovascular neurons in both the
      groups and the increase was also significantly greater in SIH than in the
      normotensive group. On the other hand, iontophoretic application of ST-A II
      inhibited the ENG of Hb cardiovascular neurons in the two groups and the
      inhibition was markedly greater in SIH than in the normotensive rats. It is
      suggested that central A II is involved in SIH and Hb cardiovascular neurons of
      SIH show an enhanced sensitivity to A II.

PMID- 11951122
TI  - Effects of ketamine on neuronal activity of the spinal dorsal horn   in rats with
      unilateral hindpaw inflammation.
AB  - A total of 32 units were extracellularly recorded from the spinal dorsal horn of
      rats. Unitary discharges evoked by stimulation of A and C fiber in ipsilateral
      lateral and medial plantar nerve were increased after carrageenan injection to
      the plantar area. The evoked responses to both A and C fiber were significantly
      decreased or even disappeared after administration of ketamine. The windup
      phenomenon was observed in neurons located deeply in the dorsal horn following
      carrageenan injection and was significantly suppressed or abolished after
      ketamine administration. The results above show NMDA receptor appears to be
      involved in the increase of excitability and the development of windup phenomenon
      in the spinal cord dorsal horn associated with carrageenan induced inflammation.

PMID- 11951124
TI  - Hepatic safety of itraconazole.
AB  - BACKGROUND: As the use of the newer oral antifungal agents for the treatment of
      superficial fungal infections becomes more widespread, the issue of safety
      surrounding their use is becoming an increasingly important consideration.
      Itraconazole is effective and well tolerated, with most side effects being minor
      and reversible. The most common adverse events are gastrointestinal upset,
      headache, and transient skin reaction. There have also been rare reports of
      hepatitis. OBJECTIVE: To assess the hepatic safety of pulse and continuous
      itraconazole in the treatment of onychomycosis. METHODS: An analysis was
      performed on all itraconazole clinical trials sponsored by Janssen Research
      Foundation in the treatment of onychomycosis, where there was an assessment of
      laboratory safety. A review of the published literature was also undertaken to
      assess the hepatic safety of itraconazole in common practice. RESULTS: The data
      indicate that itraconazole pulse treatment is safe, with no significant
      differences in the number of code 4 abnormalities (baseline value is in the
      normal range and at least two values, or the last testing in the observation
      period, exceed twice the upper limit of normal) in the liver function parameters
      studied: alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      alkaline phosphatase, and total bilirubin. The incidence of all the code 4
      abnormalities was below 2%. In the literature there are reports of symptomatic
      hepatitis with itraconazole continuous therapy but no published report of
      symptomatic hepatotoxicity using the pulse regimen. CONCLUSIONS: Itraconazole
      pulse therapy for onychomycosis appears to be safe, especially from the
      perspective of potential liver damage. In the itraconazole package insert liver
      function tests are recommended for patients receiving continuous itraconazole for
      periods of time exceeding 1 month. There is no such monitoring requirement for
      the pulse regimen unless the patient has a history of underlying hepatic disease,
      the liver function tests are abnormal at baseline, or at any time that there is
      the development of signs or symptoms suggestive of liver dysfunction.

PMID- 11951125
TI  - The genes and genetics of malignant melanoma.
AB  - BACKGROUND: Population-based studies have identified several clinical variables
      associated with an increased risk of developing cutaneous melanoma that include
      phenotype, amount of and response to sun exposure, and family history. However,
      these observations are of limited relevance to clinical practice as the risk
      associated with each factor is individually modest and the characteristics of
      these variables lack precision when applied to a particular individual.
      OBJECTIVE: To review the literature regarding recent advances made in the
      understanding of the genes and genetics of clinical variables associated with an
      increased risk of melanoma. CONCLUSION: Variants of the MC1R (melanocortin-1
      receptor) have been identified as major determinants of high-risk phenotypes,
      such as red hair and pale skin, and the ability to tan in response to UV
      exposure. Several studies also suggest that such variants may increase melanoma
      risk independent of their contribution to phenotype. A strong genetic basis for
      both nevus density and size has been demonstrated and the link between nevi and
      the development of MM has become better defined. Finally, germline defects in
      several genes involved in cell cycle regulation, namely, p16 and CDK4, have been
      demonstrated in many familial melanoma kindreds. This progress has introduced the
      prospect of genetic testing as a means of identifying a limited number of high
      risk individuals who can be targeted with regular screening and education
      regarding UV exposure and skin self-examination. Ultimately, through rational
      genetic therapy targeted to correcting the underlying molecular defect, altering
      the natural history of melanoma development may be possible.

PMID- 11951126
TI  - The majority of cutaneous squamous cell carcinomas arise in actinic keratoses.
AB  - BACKGROUND: Retrospective studies have given conflicting results with respect to
      how many cutaneous squamous cell carcinomas (SCCs) arise in actinic keratoses
      (AK). OBJECTIVE: This study was conducted to determine what percentage of SCCs
      arise in AKs and to obtain more information about two histological features of
      SCCs, namely, thickness and ulceration. METHODS: A prospective study was done of
      all SCCs treated by the authors during one calendar year. RESULTS: Two hundred
      eight patients with SCC were entered into the study. An AK was contiguous with an
      SCC in 72% of the cases. This was taken as evidence that the SCC arose in the AK.
      Men presented with thicker and more ulcerated SCCs than women, but these were not
      statistically significant: p = 0.06 for thickness and p = 0.07 for ulceration.
      Ulcerated SCCs were more likely to arise on the head and neck (p = 0.02), on
      patients who had multiple skin cancers (p = 0.005), and on patients who had a
      family history of skin cancer (p = 0.03). CONCLUSION: Actinic keratoses need to
      be removed before they turn into SCCs. The prognostic significance of ulceration
      of cutaneous SCCs needs to be determined.

PMID- 11951127
TI  - Rare presentations of basal cell carcinoma.
AB  - BACKGROUND: Even though basal cell carcinomas (BCC) are the most common skin
      cancers in the world, they rarely appear in the African-American, Hispanic, and
      Asian populations. BCCs most commonly present on the head and neck of elderly,
      light-skinned individuals who have received an excessive amount of sun exposure.
      However, it has been hypothesized that the development of BCCs in unusual
      populations is a result of an alteration in tumor surveillance or an impairment
      in cellular immunity. OBJECTIVE: We present two cases of BCC, one in an Asian
      woman and one in an African-American woman. Neither of these patients had any
      history of genodermatoses or were immunocompromised. CONCLUSION: BCCs can occur
      in Asian and African-American patients. Clinicians should include the diagnosis
      of BCC in their differential for these patients despite their rare presentations.

PMID- 11951128
TI  - The skin in pregnancy.
AB  - BACKGROUND: Physiologic skin changes are common during pregnancy due to a
      temporary shift in hormonal, metabolic, and immunologic factors. Physicians may
      mistake normal skin changes in pregnancy as pathologic change within the skin,
      and so an appreciation of the common and less common skin manifestations will
      assist in appropriate patient care. OBJECTIVE: This review highlights the normal
      physiologic skin changes in pregnancy, which include pigmentary changes, changes
      to the hair and nails, alterations in glandular activity, vascular and
      hematological changes, cutaneous tumors, and mucous membrane changes. CONCLUSION:
      Physiologic changes to the skin in pregnancy can be complex and confusing.
      Pregnancy can be a stressful time for women so it is imperative that physicians
      be aware of the normal skin changes during pregnancy in order to prevent
      unnecessary investigations and treatments.

PMID- 11951130
TI  - Primary localized cutaneous amyloidosis in association with papillary thyroid
      carcinoma.
AB  - BACKGROUND: Lichen amyloidosis, a type of primary localized cutaneous
      amyloidosis, is characterized by pruritic brown or grayish pigmented papules.
      OBJECTIVE: We report a case of lichen amyloidosis in which the skin lesion
      consisted of asymptomatic salmon-pink-colored papules on the back of the neck to
      the upper back. This was different from typical clinical pictures of lichen
      amyloidosis. Our patient proved to have thyroid papillary carcinoma. CONCLUSION:
      Our case may suggest that lichen amyloidosis could be a cutaneous manifestation
      of thyroid cancers.

PMID- 11951129
TI  - The use of diphenylcyclopropenone in the treatment of recalcitrant warts.
AB  - BACKGROUND: The treatment of recalcitrant palmoplantar and periungual warts using
      topical immunotherapy with diphenylcyclopropenone (DPC) was reviewed
      retrospectively over a seven-year period. METHODS: Two hundred eleven patients
      were sensitized during this time. The patients consisted of 90 males and 121
      females and were between 5 and 78 years old. Twenty-three patients were lost to
      followup. Of the remaining, 4 were undergoing treatment at the time of
      evaluation, 1 patient failed sensitization, and 1 patient became pregnant. Four
      discontinued because of side effects, 3 because of financial reasons, and 18
      patients discontinued treatment prior to completing the minimum required
      applications (defined as 6), producing a dropout rate of 12% (25/211). Three
      patients had additional treatment during the course of DPC and were not included
      in the study. The remaining 154 patients were classified as nonresponders or
      responders. RESULTS: The responders consisted of 135 individuals (87.7%) that had
      complete clearance of warts. Reported adverse effects were local and included
      with pruritus (15.6%), with blistering (7.1%), and with eczematous reactions
      (14.2%). The majority of the patients tolerated the treatment very well. One
      patient developed local impetigo. Patients had an average of 5 treatments over a
      6-month period. CONCLUSIONS: Topical immunotherapy using DPC is an effective
      treatment option for recalcitrant warts. It should be considered as first-line
      treatment for warts based on its high response rate, absence of scarring, and
      painless application.

PMID- 11951131
TI  - Cutaneous manifestations of eating disorders.
AB  - BACKGROUND AND OBJECTIVE: No complete review of the cutaneous manifestations of
      eating disorders exists. We therefore, set out to review and systematically
      describe the clinical and histopathologic features of dermatologic conditions
      associated with anorexia nervosa, bulimia nervosa, and obesity. Differential
      diagnosis, pathophysiology, laboratory studies, and treatment are also reviewed.
      METHODS: Index Medicus review (1966 to present) using Ovid-MEDLINE. Search terms
      included eating disorders, anorexia nervosa, bulimia nervosa, eating disorders
      not otherwise specified (ED-NOS), and obesity, as well as the terms dermatology
      skin and cutaneous manifestations, with cross-referencing sources. These were
      combined with our own clinical experience. All relevant publications, including
      case reports, case series, cohort studies, and histopathologic studies giving at
      least Level II-3 evidence (evidence from comparisons between times or places with
      or without the intervention, including dramatic results in uncontrolled
      experiments), were selected. CONCLUSION: Forty dermatological signs have been
      reported in eating disorder patients. Eating disorders have many cutaneous
      manifestations and cutaneous signs may lead to the diagnosis of an occult eating
      disorder. The resolution of skin eruptions in eating disorder patients often
      depends on treatment of the underlying disorder.

PMID- 11951132
TI  - Kasabach-merritt syndrome.
AB  - BACKGROUND: Kasabach-Merritt syndrome (KMS) is a consumptive coagulopathy
      associated with the presence of a large vascular lesion. It is often a
      frustrating condition to treat and it carries a high mortality rate. There are
      currently no known treatment guidelines. Kasabach-Merritt syndrome is associated
      with kaposiform hemangioendothelioma (KHE) and tufted angioma (TA); these
      lesions, when associated with KMS, are locally invasive, aggressive vascular
      tumors. Treatment options include supportive care, local therapies, and drug and
      surgical management. In most recent case reports, a multimodal approach to
      therapy is taken. OBJECTIVE AND CONCLUSION: The objective of this article is to
      provide a comprehensive review of KMS and give an up-to-date summary of treatment
      options. The clinical presentation, laboratory findings, vascular pathology, and
      pathophysiology will also be discussed.

PMID- 11951133
TI  - Vulval disease from the 1800s to the new millennium.
AB  - BACKGROUND: The study of vulval disease has become important over the last few
      decades. Although several inflammatory dermatoses were described at the end of
      the 19th century, vulval involvement in these conditions was only realized some
      time later. Indeed, the vulva may be a site of predilection of some inflammatory
      dermatoses such as lichen sclerosus. OBJECTIVE: There are now groups of
      interested dermatologists, gynecologists, and genitourinary physicians that have
      cooperated to study patients with vulval disease. Hopefully, this will increase
      our knowledge over the next century. CONCLUSION: This review article examines
      vulval disease from an historical viewpoint and highlights important developments
      that have increased our understanding of the disorders that specifically affect
      the vulva.

PMID- 11951134
TI  - [Biliary tract diagnosis using nuclear spin tomography--not always, but always
      more often!].

PMID- 11951135
TI  - [The value of magnetic resonance cholangiography for the expedient diagnosis of
      choledocholithiasis].
AB  - INTRODUCTION: Management of symptomatic cholecystolithiasis is vitally influenced
      by dilated biliary tract and choledocholithiasis. The objectives of this
      prospective pilot study were to evaluate the diagnostic value of preoperative
      magnetic resonance cholangiography (MRC) compared to diagnostic endoscopic
      retrograde cholangiography (ERC) and to establish an efficient algorithm for
      diagnostics and treatment of choledocholithiasis. METHODS: All consecutive
      patients with cholecystolithiasis and dilated biliary tract proven by sonography
      as well as elevated liver function tests were enrolled within 12 months. Patients
      without evidence of bile duct calculi underwent preoperative MRC, whereas
      patients with choledocholithiasis immediate ERC. RESULTS: 58 patients (30 male,
      28 female) with a median age of 59.4 years underwent preoperative MRC. In 18
      patients (10 male, 8 female; median age 63.5 years) with evidence of
      choledocholithiasis we subsequently performed ERC and papillotomy. Bile duct
      stones were detected and removed after papillotomy in 10 patients, whereas
      calculi could not be found anymore in 8 patients. The remaining 40 patients
      without calculi evident on MRC were transferred to magnetic resonance tomography
      and ERC in case of suspected malignancy or to cholecystectomy and intraoperative
      cholangiography (IOC), which could definitely exclude choledocholithiasis. In
      comparison to ERC respectively IOC, MRC was able to detect bile duct stones with
      a sensitivity of 100% and a specificity of 83.3%. CONCLUSIONS: Non-invasive MRC
      seems to replace diagnostic ERC concerning the presence of choledocholithiasis in
      case of cholecystolithiasis and dilated biliary tract with a high sensitivity.
      The preoperative ERC with stone extraction is still the therapy of choice in case
      of radiologically confirmed choledocholithiasis.

PMID- 11951136
TI  - [Recent data for frequency of autopsy in Germany].
AB  - BACKGROUND AND OBJECTIVE: : Today clinico-pathological autopsies serve as a
      measure of quality assurance in clinical medicine. Furthermore reliable
      information on the distribution of different causes of death can only be gained
      by a significant autopsy rate. Medicolegal autopsies are essential for the
      discovery of non-natural or violent deaths. This study provides information on
      changes in clinico-pathological and medicolegal autopsy rates between 1994 and
      1999. METHODS: : A survey of autopsy rates in 1994 and 1999 was undertaken
      covering all German pathological and medicolegal institutes. The autopsy figures
      of the different states were analysed separately. Most autopsies performed in
      pathological institutes were clinico-pathological autopsies and almost all
      autopsies performed in Institutes of Legal Medicine were medicolegal autopsies.
      RESULTS: Between 1994 and 1999 the frequency of clinico-pathological autopsies
      decreased from about 4 % to 3 % of all deaths. The medicolegal autopsy rate
      remained stable on a low level at about 2 %. The differences between various
      states are up to 4-fold for clinico-pathological autopsies and up to 5-fold for
      medicolegal autopsies. CONCLUSIONS: : The autopsy rates in Germany are
      frighteningly low compared to other European countries. Considering the dramatic
      decline of clinico-pathological autopsy rates the role of the post-mortem
      examination as a control of clinical medicine and death statistics cannot be
      fulfilled properly. The low medicolegal autopsy rate is responsible for the high
      number of undetected non-natural or violent deaths.

PMID- 11951137
TI  - [28-year-old patient with hypokalemic paralysis].

PMID- 11951138
TI  - [Celecoxib].

PMID- 11951139
TI  - [Anemia in chronic inflammatory intestinal disease: an often underestimated
      problem].

PMID- 11951140
TI  - [Infections by Bacillus anthracis].

PMID- 11951141
TI  - [Varicella during pregnancy].

PMID- 11951142
TI  - [Is there a classification of degrees of severity for a restrictive respiratory
      disorder?].

PMID- 11951143
TI  - [New indication for thalidomide?].

PMID- 11951144
TI  - A case control study on psychopharmacotherapy before suicide committed by 61
      psychiatric inpatients.
AB  - OBJECTIVE AND METHOD: The pharmacotherapy of 61 suicide victims (0.24 % of 27,078
      admissions from January 1, 1980 to December 31, 1999) was compared to that of a
      control group matched for age, gender and diagnosis at the time of discharge.
      RESULTS: Both groups were also comparable regarding stay in hospital, history of
      psychiatric disease, and frequency of hospitalisations during the year preceding
      the index evaluation. Multiple but not single suicide attempts were significantly
      more frequent in patients who were later to complete the suicide than in
      controls. Schizophrenia (ICD-9, ICD-10) was the most frequent diagnosis among
      suicide victims (44.3 %). Affective psychosis (ICD-9, ICD-10) bore the highest
      relative risk (0.8 %). 50 % of the schizophrenic patients in the suicide group
      had been continuously treated with full-dose tricyclic antidepressants. The CPZ
      equivalents in the patients treated with antipsychotics were not of
      discriminating value. Four of 27 schizophrenic patients in the suicide group had
      been off neuroleptics for ten days or more; this was never observed among the
      controls. Lorazepam applied in 40% of the schizophrenic and in 25 % of the
      affective psychosis suicide victims had more often been withdrawn or reduced
      during the ten days preceding suicide than among controls. No schizophrenic
      suicide victims but five controls had been on mood stabilisers. The use of
      antipsychotics (classical and atypical) and a recent change in tricyclic drug or
      drug dose were more frequent in suicide victims with affective psychosis. Lithium
      had been given to one patient, but it had also been administered to six controls;
      this difference is significant. CONCLUSION: Mood stabilisers, especially lithium,
      should be considered more often in patients with previous suicide attempt(s).
      When changing antidepressants in affective psychosis, benzodiazepines might be
      given more deliberate consideration. Patients in all diagnostic categories should
      be closely guided by means of intensified psychotherapeutic interventions while
      undergoing a benzodiazepine reduction. The treatment of patients suffering from
      schizophrenia with full-dose tricyclic regimens should be considered as possibly
      enhancing the acute suicide risk in some individuals.

PMID- 11951145
TI  - Concretism in biological suicide research -- are we eating the menu instead of
      the meal? Some thoughts on present research strategies.
AB  - Research into serotonergic parameters associated with suicidal behaviour has
      resulted in many inconsistent and ambiguous findings. In this mini-review, we
      have tried to name some examples of methodological and conceptual vagueness and
      pitfalls in biological suicide research. The existing literature indicates
      various critical issues considered when interpreting existing data in this area: 
      - The 'suicidality' construct is not useful in biological suicide research.
      Autodestructive tendencies mostly occur in suicide completers and are probably
      not found in many suicide attempters and individuals with suicidal thoughts. No
      consistent association has been found between suicide intent and injury, suicide
      intent and suicide risk, choice of suicide method (violent vs. non-violent) and
      suicide risk, suicidal thoughts or attempted suicide. No close relationship
      between different degrees and different forms of suicidal behaviour has yet been
      demonstrated with any degree of consistency. According to many studies,
      serotonergic markers do not correlate with the various qualities and intensities
      of suicidal behaviour. -- The association between suicidality and impulsivity or
      aggression is weak. There probably is a disturbance in impulse and aggression
      control, but only in a subgroup of'suicidal' patients. -- It might be misleading
      to use nosological constructs of depression in order to characterize suicidal
      individuals in biological suicide research. Biological variables might be
      associated with specific depressive symptoms, but not with some nosological
      construct or the sum score of a depression rating scale. -- The alleged
      association between peripheral and central serotonergic parameters is based on
      assumptions for which there is insufficient proof. Several studies indicate that
      there is no correlation between changes in central and peripheral serotonergic
      parameters. The mechanism of changes of peripheral serotonergic parameters is not
      sufficiently understood.

PMID- 11951146
TI  - Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a
      randomized crossover trial.
AB  - Anecdotal reports in Tourette's syndrome (TS) have suggested that marijuana
      (cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major
      psychoactive ingredient of marijuana, reduce tics and associated behavioral
      disorders. We performed a randomized double-blind placebo-controlled crossover
      single-dose trial of Delta(9)-THC (5.0, 7.5 or 10.0 mg) in 12 adult TS patients.
      Tic severity was assessed using a self-rating scale (Tourette's syndrome Symptom
      List, TSSL) and examiner ratings (Shapiro Tourette's syndrome Severity Scale,
      Yale Global Tic Severity Scale, Tourette's syndrome Global Scale). Using the
      TSSL, patients also rated the severity of associated behavioral disorders.
      Clinical changes were correlated to maximum plasma levels of THC and its
      metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor
      Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). Using the TSSL, there
      was a significant improvement of tics (p=0.015) and obsessive-compulsive behavior
      (OCB) (p = 0.041) after treatment with Delta(9)-THC compared to placebo. Examiner
      ratings demonstrated a significant difference for the subscore "complex motor
      tics" (p = 0.015) and a trend towards a significant improvement for the subscores
      "motor tics" (p = 0.065), "simple motor tics" (p = 0.093), and "vocal tics" (p =
      0.093). No serious adverse reactions occurred. Five patients experienced mild,
      transient side effects. There was a significant correlation between tic
      improvement and maximum 11-OH-THC plasma concentration. Results obtained from
      this pilot study suggest that a single-dose treatment with Delta(9)-THC is
      effective and safe in treating tics and OCB in TS. It can be speculated that
      clinical effects may be caused by 11-OH-THC. A more long-term study is required
      to confirm these results.

PMID- 11951147
TI  - Spontaneous recurrence of methamphetamine-induced paranoid-hallucinatory states
      in female subjects: susceptibility to psychotic states and implications for
      relapse of schizophrenia.
AB  - In this study, we examined the relationship between increased sensitivity to
      stress associated with noradrenergic hyperactivity and dopaminergic changes, and
      susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP)
      psychosis (i.e., flashbacks). The subjects were 81 physically healthy females.
      Plasma monoamine metabolite levels were assayed in: 19 flashbackers, of whom 11
      experienced a single flashback and 8 exhibited subsequent flashbacks; 20 non
      flashbackers with a history of MAP psychosis; 8 subjects with persistent MAP
      psychosis; and 23 MAP users and 11 non-user controls. All 19 flashbackers had
      undergone frightening and stressful experiences during previous MAP use. Mild
      psychosocial stressors then triggered their flashbacks. During flashbacks, plasma
      norepinephrine levels increased, with a small increase in plasma levels of 3
      methoxytyramine, which is an index of dopamine release. Among the 19
      flashbackers, the 8 with subsequent episodes had increased NE levels and slightly
      increased 3-methoxytyramine levels, while the 11 with a single episode displayed
      small increases in norepinephrine and 3-methoxytyramine levels. Thus,
      noradrenergic hyperactivity and increased dopamine release in response to mild
      psychosocial stressors may be responsible for the development of flashbacks.
      Robust noradrenergic hyperactivity with slightly increased DA release in response
      to mild stress may induce susceptibility to subsequent flashbacks. Flashbacks and
      schizophrenia may share the pathophysiology of susceptibility to recurrence of
      paranoid-hallucinatory states such as stress sensitization, and also
      noradrenergic hyperactivity and enhanced DA release. Thus, flashbacks may provide
      an appropriate model of susceptibility to paranoid-hallucinatory states of
      schizophrenia. The model psychosis is a potential tool for validating basic
      neurobiological concepts thought to be related to the schizophrenia. A better
      understanding of the neurobiological mechanisms of susceptibility to recurrence
      could provide useful information in the development of strategies for preventing
      relapse.

PMID- 11951148
TI  - Development of obsessive-compulsive behaviour following cortisone treatment.
AB  - In this report, we will describe the first case of obsessive-compulsive behaviour
      following oral corticosteroid treatment in a 75-year old adult male patient with
      pulmonary disease, but without previous psychiatric symptoms or organic brain
      disorder. We will also discuss the clinical and pathophysiological
      considerations.

PMID- 11951149
TI  - Successful treatment of recurrent brief depression with reboxetine -- a single
      case analysis.
AB  - Recurrent Brief Depression (RBD) is a prevalent condition among the depressive
      illnesses, and is characterized by depressive episodes of a few days' duration
      occurring almost every month that are unrelated to the menstruation cycle. So
      far, RBD has not been shown to respond to antidepressive treatment in controlled
      clinical trials with citalopram, fluoxetine, flupenthixol, paroxetine, or
      mianserin using a "classical" parallel group design. However, successful RBD
      treatment on about sixty patients has so far been reported in one open trial with
      fluoxetine and in several cases with lithium, mirtazapine, and tranylcypromine.
      Furthermore, successful treatment of RBD has been reported in a few patients with
      carbamazepine, nimodipine, and verapamil in controlled double-blind single-case
      analyses using a flexible cross-over design.

PMID- 11951150
TI  - Sexual dysfunction caused by reboxetine.
AB  - The author reports on self-experienced, reboxetine-induced sexual dysfunction
      (prolonged orgasm of reduced intensity) and seminal emission after defecation.
      Both disorders were accompanied by pain and ceased within two days after
      discontinuation of the drug.

PMID- 11951151
TI  - Rivastigmin and impaired motor function.
AB  - In this case study, we describe the case of an 88-year-old female patient
      diagnosed with Alzheimer's disease who developed a severe motor dysfunction as a
      side effect of rivastigmin treatment. There have been reports on motor
      dysfunctions caused by other choline esterase inhibitors.

PMID- 11951152
TI  - Soyka M, Bottlender R, Moller H-J; Epidemiological evidence for a low abuse
      potential of zolpidem; Pharmacopsychiatry 2000, 33: 138 - 141.

PMID- 11951155
TI  - [Tobacco advertising that endangers children].

PMID- 11951154
TI  - [Cardiac pacing as universal remedy in sleep related breathing disorders?].

PMID- 11951156
TI  - [Validity of nonspecific bronchial provocation tests for the diagnosis of airway
      hyperresponsiveness--a comparison of different methods].
AB  - OBJECTIVE: To compare the validity of different methods for the assessment of
      bronchial hyperresponsiveness used by different centers. METHODS: Case series of
      648 subjects referred to six pulmonary centers, all with a history of shortness
      of breath without airway obstruction, without use of medication that might
      influence the tests and without viral infections during the previous two weeks.
      All subjects answered a questionnaire of recent symptoms and underwent bronchial
      challenge with a chemical stimulus according to each center's protocol. Analysis
      was performed by receiver operating characteristic (ROC) plots using the
      questionnaire's answers as the gold standard. Diagnostic test sensitivities at
      the cut-offs for bronchial hyperresponsiveness indicated by each center were
      compared. RESULTS: ROC plots showed poor validity of all tests, i.e. both
      acceptable sensitivity and specificity were not observed with any test. There was
      no obvious difference of the slope of the ROC plots between the different
      centers. However, maximal sensitivity differed considerably: for "wheeze during
      the previous 12 months", sensitivity at each center's cut-off for the definition
      of bronchial hyperresponsiveness varied between 0.35 and 0.73. The choice of the
      question used as the standard had little influence on test validity. CONCLUSION:
      Although some of the differences between centers may be explained by subject
      characteristics, the large differences of the test sensitivities are unacceptable
      and underscore the need for standardization of these tests, primarily with
      respect to sufficient sensitivity.

PMID- 11951157
TI  - [Acceptance of peak-flow measurement in out-patients].
AB  - There are a lot of indications for PEF-measurement of which the long-time
      observation of asthmatics is the most important one. Unfortunately not all
      patients are measuring regularly. The acceptance of PEF-measurement in patients
      who have got a PEF-monitor should be found out by a questioning in the following
      trial. METHOD: 65 patients who have got a prescription for a PEF-monitor since
      1995 were asked to answer a questionnaire anonymously. RESULTS: 49 patients (24
      female, 24 male, 1 without information) answered the questionnaire. 19 patients
      are still measuring, 30 patients stopped measuring because of lacking complaints.
      Patients measured regularly (n = 14). 4 irregularly, most frequently daily (n =
      9), more rarely only weekly, monthly or casually, Measuring was done mostly in
      the morning (n = 8), 3 times a day (n = 5), 2 times at same time (n = 9). 11
      patients measured before inhalation of a beta-agonist, 8 patients before and
      after inhalation as well. 7 patients recorded the values. Causes for measuring
      mostly were control and complaints. CONCLUSION: PEF-Measuring obviously will be
      accepted if the patient understands the necessity, f.e. for a short period of
      time at a moment of complaints or start or change of therapy. Under those
      circumstances most of our patients will be ready to do PEF-measurement regularly
      and daily and two to three times a day and at the same time and eventually with
      recording the values.

PMID- 11951159
TI  - [Children-orientated tobacco advertising in Germany].
AB  - Since 1990 the percentage of smokers among the 12 to 17-year-olds in Germany has
      risen from 21 % to about 28 %. Most of them start between the age of 11 and 13.
      85 % favour a certain brand by the age of 18. Despite the prohibition of tobacco
      commercials on radio and TV the cigarette industry has continually increased
      their budget for advertising aimed more and more at women and children. According
      to the author's knowledge, this report describes for the first time the
      strategies most frequently applied in Germany to incite children and teenagers to
      smoking. The publicity campaigns are not restricted to billboards and the printed
      press, but use the internet also. Indirect conditioning to a certain brand by
      music videos, movies and merchandising of attractive clothes and trips as well as
      the sponsoring of special music and sports events are also shown.The report
      analyses and evaluates examples of messages in printed advertisements aimed at
      children. With psychological skill interest in smoking is created with teenagers
      and a conditioning for smoking in certain situations is promoted.

PMID- 11951158
TI  - [Effects of a high intensity training program on patients with chronic
      obstructive airways disease (COAD)].
AB  - In a controlled/prospective clinical trial we examined 125 patients with moderate
      COAD, 84 of which performed a high-intensity training program on cycle
      ergometers. METHODS: All participants (controls n = 39, training-group n = 84,
      age 48.7 versus 48.1 years, FEV1 62.3 % vs. 63.1 % of predicted) were examined
      spiroergometrically (ramp protocol, increment 10 W/min), the anaerobic threshold
      (AT) determined and a training intensity calculated (AT + 40 % of the difference
      to peak exercise). Training was carried out on cycle ergometers with 5 training
      units weekly at 40 minutes each. We aimed at a minimum of 22 training units
      during 4 weeks. RESULTS: Both groups improved in the lung function at rest (FEV1
      + 11 % versus + 12 % in the controls). Only for the training group we found a
      statistically significant improvement in maximum exercise capacity (O2 uptake +
      286.4 ml vs. + 72.4 ml, maximum workrate + 20.0 watts vs. + 5.7 W), of the
      anaerobic threshold (AT improved by 8.4 watts vs. 5.1 W) as well as in the
      metabolic load (lactate decreased by 1.3 mmol vs. 0.2 mmol, ventilation decreased
      by 3.8 l/min vs. 2.3 l/min). In most subscales of the SF-36 questionnaire quality
      of living improved more clearly in the training group, whereas the LAQ
      questionnaire showed no group-specific differences and no improvement after
      training. CONCLUSION: We conclude from the result that a high intensity training
      program can be recommended as a useful and low-risk component in pulmonary
      rehabilitation programs.

PMID- 11951160
TI  - [Evaluation of mechanical and neurophysiological effects of wearing bandages for
      the knee joint in functional testing situations].
AB  - The purpose of the study was to estimate the stabilising effects of two
      functional bandages for the knee joint. Two mechanisms typically leading to knee
      injuries were simulated. Three-dimensional recordings of knee joint angles and
      recordings of the tibial displacement in anterior-posterior direction were used
      to determine the destabilisation of the knee joint as a result of the applied
      mechanical stimuli, as well as the stabilising support of wearing the bandages.
      Reflex activations of the knee joint muscles and their modulation by the bandages
      were measured by EMG. To estimate limitations of the sports performance by the
      bandages, the subjects performed an additional test for postural stability. The
      testing performance, the three-dimensional knee joint angles and muscle
      activities were measured. While the FUTURO(R)-knee joint bandage (BDF AG) caused
      both mechanical and neurophysiological effects, the action of the KASSELER
      bandage (Sporlastic(R) GmbH) relied solely on the enhancement of muscular
      activities. The applied methods proved to be a very useful tool for the
      evaluation of stabilising effects of bandages in functional situations.

PMID- 11951161
TI  - [Tibial tunnel enlargement after arthroscopic anterior cruciate ligament
      reconstruction].

PMID- 11951162
TI  - [Physical activity after shoulder arthroplasty].
AB  - A hemi- or total shoulder arthroplasty was performed in 171 patients between 1992
      and 1997. We examined 118 patients under the age of 70 regarding their level of
      physical activity. For a pre- and postoperative comparison we divided the
      patients in two groups. Group one included all patients with osteoarthritis,
      rheumatoid arthritis, instability associated arthritis, avascular necrosis and
      other arthropathies. Group two included acute fractures and fracture sequelae.
      The postoperative outcome was functionally assessed by using the Constant score.
      There was an average Constant score of 60,9 for group one and 67,1 for group two.
      Both groups showed a domination of activities with motion patterns unspecific for
      the shoulder. There were more patients in group two reporting activities which
      depend on a good or very good shoulder function. There is no general estimation
      for the ability to be active in sports after shoulder arthroplasty. An individual
      assessment of the shoulder function is essential. Important criterias beside
      motivation and age are the status of the rotator cuff and the soft tissue
      balancing. The correct indication for shoulder arthroplasty as well as the
      preoperative planning and the postoperative rehabilitation program are essential
      for a good functional outcome and the key for physical activity after shoulder
      arthroplasty.

PMID- 11951163
TI  - [Sports medicine analysis of golf "swing" and lesions occurring during golf
      practice].
AB  - Health problems as seen in golf from the viewpoint of sports medicine and
      orthopedics are described. For better understanding important phases of the swing
      are analysed in correlation with possible lesions. Golfers mostly suffer from
      lumbal spine, elbows, hands and wrists, as well as from shoulder and knee
      disorders. We must differentiate between problems of the acute injuries and
      chronic disorders, whereas degenerative problems may interfere with specific
      golfing movements and are thus aggravated. The most likely causes of muscle joint
      and bone disorders are overuse, inadequately trained muscles and poor technique.

PMID- 11951164
TI  - [Tibial diaphyseal fracture in sports - clinical outcome and sports ability after
      operative treatment].
AB  - Sports-related tibial diaphyseal fractures occur mainly in contact sports and in
      downhill skiing. Due to the demand for rapid healing and the need for an early
      recovery of the mostly young patients, surgery is almost imperative. The clinical
      outcome and sports ability of 38 patients with sports-related tibial diaphyseal
      fractures were investigated 29 months after the initial trauma. Soccer and
      wintersport accounted for the majority of injuries. Operative treatment has been
      mainly unreamed nailing. After an average of 10.3 months 32 patients (84 %)
      returned to sports. Almost one-third, however did change over to a less stressful
      sport. 6 patients discontinued their sports activity. The activity score of
      Tegner and Lysholm declined from 5.4 before the injury to 3.4 six months after
      surgery. At the time of the follow-up examination this rose to 4.6. The long-term
      result scored after Merchant and Dietz showed 87 % excellent and good results.
      For the majority of sports-related tibial diaphyseal fractures, unreamed nailing
      is the treatment of choice.

PMID- 11951169
TI  - The neuroanatomy of attention.
AB  - Attention is a complex neurobehavioral domain that is essential for all higher
      functions. Large areas of the brain are devoted to attention, reflecting its
      importance in the entire range of mental operations. Currently, two major
      distributed neural networks are recognized as mediating complementary aspects of
      attentional function. One is a diffuse system that distributes attention
      globally. This attentional system is subserved by a widespread network of
      thalamic and bihemispheric structures in which the frontal lobes are particularly
      important. The second network, a focal system that distributes attention to
      salient aspects of spatial experience, is lateralized to frontal and parietal
      regions of the right hemisphere. Both attentional networks are comprised of
      cortical and subcortical gray matter structures, as well as connecting white
      matter tracts that integrate these regions into functional ensembles.
      Neurological disorders frequently produce dramatic syndromes reflecting
      dysfunction of these networks. Among these syndromes are the acute confusional
      state, which results from disturbance of the diffuse system, and left neglect,
      which follows disruption of the right hemisphere system. The neuroanatomy of
      attention is crucial for understanding important neurobehavioral syndromes and
      their treatment.

PMID- 11951170
TI  - Forms of attention and attentional disorders.
AB  - Difficulties in attention or concentration are observed in many clinical
      syndromes. Cognitive studies of normal attention and neuropsychological studies
      of brain dysfunction indicate that attention reflects a variety of mechanisms.
      These processes include the startle response, the orienting response, selective
      attention, vigilance, and divided attention. Understanding the specific
      mechanisms involved in attention deficits or lapses may be helpful in planning
      and evaluating remediation programs and in altering patients' environments to
      compensate for specific attention deficits. In this article, forms of attention
      and disorders of attention are discussed, with emphasis on their importance to
      every day activities.

PMID- 11951165
TI  - [Bilateral stress fracture of the medial femoral neck].

PMID- 11951171
TI  - Attention deficits in aphasia: presence, nature, assessment, and treatment.
AB  - Recently, there has been growing interest in understanding how nonlinguistic
      cognitive problems such as impaired attention might negatively affect the
      linguistic abilities of adults with aphasia. This article begins with a summary
      of research focused on the relationship between attention and language
      impairments in aphasia and a discussion of why it might be important for
      clinicians to address the attention abilities of their aphasic patients. Also
      discussed are formal and informal measures for quantifying and qualifying
      attention problems, treatment strategies for directly or indirectly remediating
      attention problems in patients with aphasia, and empirical support for such
      treatment.

PMID- 11951172
TI  - Unilateral neglect: a disorder of attention.
AB  - Unilateral neglect is a complex disorder that occurs most frequently in patients
      with right hemisphere damage. Although it is most severe in the acute phase, it
      may be detectable in some patients many months and even years after onset. Its
      presence is usually obvious in functional activities, including reading and
      writing, and it has consistently been identified as a negative predictor for
      recovery of independence in daily living. The purposes of this article are to
      review common neglect symptoms, summarize current theories of neglect, outline
      appropriate assessment tasks, and describe several treatment approaches for left
      unilateral visual neglect.

PMID- 11951173
TI  - Attention impairment following traumatic brain injury.
AB  - The incidence of traumatic brain injury (TBI) is approximately 2,000,000 cases
      annually, and approximately 5.3 million Americans are currently living with some
      degree of cognitive-linguistic impairment secondary to TBI. One frequent aspect
      of that impairment is disordered attention. Attention is a complex system
      comprised of several component skills, each of which may be compromised by TBI
      and thus must be carefully assessed to design appropriate treatment protocols.
      Attention treatments for patients with TBI frequently involve implementing
      environmental controls and designing individualized therapy tasks that vary in
      terms of information processing demands. This article provides a summary of those
      attention impairments frequently associated with TBI and outlines assessment and
      treatment guidelines for clinicians serving TBI patients with attention problems.

PMID- 11951174
TI  - The effect of attentional dysfunction in Alzheimer's disease: theoretical and
      practical implications.
AB  - Attention may be one of the earliest cognitive abilities to change in Alzheimer's
      disease (AD), although its role has received belated recognition. This article
      discusses different aspects of attention and how these are differentially
      affected in AD. Of the various attention functions, divided and selective
      attention are particularly vulnerable. The etiology of attentional deficits in AD
      arises from damage to areas of frontal and parietal association cortex,
      disconnection between the anterior and posterior attentional networks, and
      decreased cholinergic function. Severity of illness is associated with
      attentional deterioration. Complexity or increased load of a task may further
      disrupt attentional function. Knowledge of attentional changes in AD is important
      to the understanding of disease-related changes in other cognitive domains such
      as memory, visuospatial functions, and language.

PMID- 11951176
TI  - Quantitative trait loci on chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18 control
      variation in levels of T and B lymphocyte subpopulations.
AB  - Lymphocyte subpopulation levels are used for prognosis and monitoring of a
      variety of human diseases, especially those with an infectious etiology. As a
      primary step to defining the major gene variation underlying these phenotypes, we
      conducted the first whole-genome screen for quantitative variation in lymphocyte
      count, CD4 T cell, CD8 T cell, B cell, and natural killer cell numbers, as well
      as CD4:CD8 ratio. The screen was performed in 15 of the CEPH families that form
      the main human genome genetic project mapping resource. Quantitative-trait loci
      (QTLs) that account for significant proportions of the phenotypic variance of
      lymphocyte subpopulations were detected on chromosomes 1, 2, 3, 4, 8, 9, 11, 12,
      and 18. The most significant QTL found was for CD4 levels on chromosome 8
      (empirical P=.00005). Two regions of chromosome 4 showed significant linkage to
      CD4:CD8 ratio (empirical P=.00007 and P=.003). A QTL for the highly correlated
      measures of CD4 and CD19 levels colocalized at 18q21 (both P=.003). Similarly, a
      shared region of chromosome 1 was linked to CD8 and CD19 levels (P=.0001 and
      P=.002, respectively). Several of the identified chromosome regions are likely to
      harbor polymorphic candidate genes responsible for these important human
      phenotypes. Their discovery has important implications for understanding the
      generation of the immune repertoire and understanding immune-system homeostasis.
      More generally, these data show the power of an integrated human gene-mapping
      approach for heritable molecular phenotypes, using large pedigrees that have been
      extensively genotyped.

PMID- 11951177
TI  - High-throughput analysis of subtelomeric chromosome rearrangements by use of
      array-based comparative genomic hybridization.
AB  - Telomeric chromosome rearrangements may cause mental retardation, congenital
      anomalies, and miscarriages. Automated detection of subtle deletions or
      duplications involving telomeres is essential for high-throughput diagnosis, but
      impossible when conventional cytogenetic methods are used. Array-based
      comparative genomic hybridization (CGH) allows high-resolution screening of copy
      number abnormalities by hybridizing differentially labeled test and reference
      genomes to arrays of robotically spotted clones. To assess the applicability of
      this technique in the diagnosis of (sub)telomeric imbalances, we here describe a
      blinded study, in which DNA from 20 patients with known cytogenetic abnormalities
      involving one or more telomeres was hybridized to an array containing a validated
      set of human-chromosome-specific (sub)telomere probes. Single-copy-number gains
      and losses were accurately detected on these arrays, and an excellent concordance
      between the original cytogenetic diagnosis and the array-based CGH diagnosis was
      obtained by use of a single hybridization. In addition to the previously
      identified cytogenetic changes, array-based CGH revealed additional telomere
      rearrangements in 3 of the 20 patients studied. The robustness and simplicity of
      this array-based telomere copy-number screening make it highly suited for
      introduction into the clinic as a rapid and sensitive automated diagnostic
      procedure.

PMID- 11951178
TI  - Early onset of severe familial amyotrophic lateral sclerosis with a SOD-1
      mutation: potential impact of CNTF as a candidate modifier gene.
AB  - Mutations in the copper/zinc superoxide dismutase 1 (SOD-1) gene are found in
      approximately 20% of patients with familial amyotrophic lateral sclerosis (FALS),
      or amyotrophic lateral sclerosis 1. Here we describe a 25-year-old male patient
      who died from FALS after a rapid disease course of 11 mo. Sequencing of the SOD-1
      gene revealed a heterozygous T-->G exchange at position 1513 within exon 5,
      coding for a V-->G substitution at position 148 of the mature protein. Genetic
      analysis of this family revealed the same mutation in both his healthy 35-year
      old sister and his mother, who did not develop the disease before age 54 years.
      Screening for candidate modifier genes that might be responsible for the early
      onset and severe course of the disease in the 25-year-old patient revealed an
      additional homozygous mutation of the CNTF gene not found in his yet unaffected
      sister. hSOD-1G93A mice were crossbred with CNTF(-/-) mice and were investigated
      with respect to disease onset and duration, to test the hypothesis that CNTF acts
      as a candidate modifier gene in FALS with mutations in the SOD-1 gene. Such hSOD
      1G93A/CNTF-deficient mice develop motoneuron disease at a significantly earlier
      stage than hSOD-1G93A/CNTF-wild-type mice. Linkage analysis revealed that the SOD
      1 gene was solely responsible for the disease. However, disease onset as a
      quantitative trait was regulated by the allelic constitution at the CNTF locus.
      In addition, patients with sporadic amyotrophic lateral sclerosis who had a
      homozygous CNTF gene defect showed significantly earlier disease onset but did
      not show a significant difference in disease duration. Thus, we conclude that
      CNTF acts as a modifier gene that leads to early onset of disease in patients
      with FALS who have SOD-1 mutations, in patients with sporadic amyotrophic lateral
      sclerosis, and in the hSOD-1G93A mouse model.

PMID- 11951179
TI  - Evidence for linkage and association with reading disability on 6p21.3-22.
AB  - Reading disability (RD), or dyslexia, is a common heterogeneous syndrome with a
      large genetic component. Several studies have consistently found evidence for a
      quantitative-trait locus (QTL) within the 17 Mb (14.9 cM) that span D6S109 and
      D6S291 on chromosome 6p21.3-22. To characterize further linkage to the QTL, to
      define more accurately the location and the effect size, and to identify a peak
      of association, we performed Haseman-Elston and DeFries-Fulker linkage analyses,
      as well as transmission/disequilibrium, total-association, and variance
      components analyses, on 11 quantitative reading and language phenotypes. One
      hundred four families with RD were genotyped with a new panel of 29 markers that
      spans 9 Mb of this region. Linkage results varied widely in degree of statistical
      significance for the different linkage tests, but multipoint analysis suggested a
      peak near D6S461. The average 6p QTL heritability for the 11 reading and language
      phenotypes was 0.27, with a maximum of 0.66 for orthographic choice. Consistent
      with the region of linkage described by these studies and others, there was a
      peak of transmission disequilibrium with a QTL centered at JA04 (chi2=9.48;
      empirical P=.0033; orthographic choice), and there was strong evidence for total
      association at this same marker (chi2=11.49; P=.0007; orthographic choice).
      Although the boundaries of the peak could not be precisely defined, the most
      likely location of the QTL is within a 4-Mb region surrounding JA04.

PMID- 11951180
TI  - Revised 14.7-cM locus for the hyperparathyroidism-jaw tumor syndrome gene, HRPT2.

PMID- 11951181
TI  - The peopling of the Americas: a second major migration?

PMID- 11951183
TI  - Increased rate of twins among affected sibling pairs with autism.

PMID- 11951184
TI  - Simplified arthroscopic suture passing using a suture loop.
AB  - Arthroscopic procedures for shoulder pathology are becoming more popular. Passing
      braided nonabsorbable suture for repair of intra-articular tissue can be
      technically difficult because advancing this suture through tissue is a 2-step
      process. The use of a suture loop with Spectrum suture hooks (Linvatec, Largo,
      FL) simplifies braided suture passing, and eliminates the use of expensive suture
      shuttles. This technique simplifies the use of nonabsorbable suture in
      arthroscopic shoulder procedures.

PMID- 11951185
TI  - Synovial osteochondromatosis of the suprapatellar bursa with an imperforate
      suprapatellar plica.
AB  - Synovial osteochondromatosis is a rare disease characterized by cartilaginous and
      osseous metaplasia of the joint synovium. While it may affect practically any
      synovial joint, the knee is most often affected. An imperforate suprapatellar
      plica is also a rare finding in the knee. We report an exceptionally rare case of
      synovial osteochondromatosis of the knee characterized by isolated multiple loose
      bodies in the suprapatellar bursa caused by imperforate suprapatellar plica in a
      52-year-old woman. The case was successfully treated by arthroscopic surgery. A
      worse-case scenario and possible diagnostic and therapeutic challenges are
      discussed.

PMID- 11951186
TI  - Overlap arthroscopic Bankart repair: reconstruction to the glenoid rim.
AB  - A new arthroscopic approach for traumatic instability has been developed with
      which avulsed capsulolabral tissue can be effectively attached to the glenoid
      articular rim with sutures, providing anatomic reattachment and effective
      deepening of the glenoid concavity similar to that achieved by open repair. This
      technique does not depend on fixation devices, trans-scapular drilling, or
      implantation of suture anchors. The fixation of the labrum using the punch-chop
      needle overlap technique (Aeratec Inc, Uniondale, NY) for reattaching torn labral
      tissue to bone allows ease of suture placement for Bankart lesion repair, with
      the fixation overlapping the rim of the glenoid. The technique presented here
      includes preparation of the glenoid rim, drilling of the glenoid tunnels, and
      peripheral suturing of the labrum.

PMID- 11951187
TI  - Medial collateral ligament reconstruction with allograft using a double-bundle
      technique.
AB  - Medial collateral ligament (MCL) reconstruction has been a topic of controversy
      in regard to the need for surgical reconstruction as well as the type of surgical
      reconstruction to be performed. Combined anterior cruciate ligament (ACL) and MCL
      reconstruction has been found to be associated with a higher incidence of
      postoperative arthrofibrosis than isolated ACL reconstruction; performing these
      reconstructions in a staged format has been proposed to avoid this devastating
      complication. We present a technique for MCL reconstruction that physiometrically
      re-establishes both anterior and posterior stabilizing components of the MCL and
      is performed with a limited soft-tissue dissection. This technique can easily be
      combined with an ACL allograft or hamstring reconstruction without need for
      staged or significantly delayed procedure. The technical details of this
      technique allow for stable fixation of an allograft reconstruction to allow for
      immediate postoperative knee range of motion with low patient morbidity because
      of the limited surgical approach.

PMID- 11951188
TI  - Arthroscopic treatment of soft-tissue impingement under the patella after total
      knee arthroplasty.
AB  - There has been an increased number of reports of complicated diseases of the
      patellofemoral joints after total knee arthroplasty (TKA). We treated soft-tissue
      impingement under the patella after TKA by arthroscopic surgery and investigated
      the findings and efficacy of the treatment. Six patients and 8 knees that showed
      soft-tissue impingement of patellofemoral joints after TKA were treated by
      arthroscopic surgery. We classified the patients with soft-tissue impingement
      under the patella into 3 groups: (I) patellar clunk syndrome, the isolated
      fibrous nodule located in the suprapatellar lesion without the other fibrous
      tissues causing the impingement (n = 2); (II) impinging hypertrophic synovitis,
      generalized hypertrophic synovitis with no fibrous nodule (n = 4); and (III) the
      combination of types I and II, the suprapatellar fibrous nodule with generalized
      hypertrophic synovitis (n = 2). Therapeutic efficacy was in type I, 2 were good
      to excellent; in type II, 3 were fair and 1 was poor; and in type III, 2 were
      fair. Better results were obtained in type I (a patellar clunk syndrome) than in
      type II (impingement synovitis).

PMID- 11951189
TI  - Hip arthroscopy: a unique inferomedial approach to bullet removal.
AB  - Most arthroscopic approaches allow for inspection of the lateral part of the hip
      joint, but visualization of the medial part is difficult. This article describes
      the removal of a bullet lodged in the right femoral head of a 33-year-old man. By
      using an inferomedial arthroscopic approach, we avoided a formal arthrotomy and
      the disadvantages of other arthroscopic approaches, which include the need for
      alternate portals, the need for traction, and the risk of both articular
      cartilage and acetabular labrum damage. The authors believe that this case
      demonstrates the effective use of the inferomedial arthroscopic approach as an
      alternative method for removing foreign bodies.

PMID- 11951190
TI  - Thermometric determination of cartilage matrix temperatures during thermal
      chondroplasty: comparison of bipolar and monopolar radiofrequency devices.
AB  - PURPOSE: To compare cartilage matrix temperatures between monopolar
      radiofrequency energy (mRFE) and bipolar RFE (bRFE) at 3 depths under the
      articular surface during thermal chondroplasty. We hypothesized that cartilage
      temperatures would be higher at all cartilage depths for the bRFE device than for
      the mRFE device. TYPE OF STUDY: Randomized trial using bovine cartilage. METHODS:
      Sixty osteochondral sections from the femoropatellar joint of 15 adult cattle
      were used for this study. Using a custom jig, fluoroptic thermometry probes were
      placed at one of the following depths under the articular surface: 200 microm,
      500 microm, or 2,000 microm. RF treatment was performed either with fluid flow
      (F) (120 mL/min) or without fluid flow (NF) (n = 5/depth/RFE device/flow; total
      specimens, 60). Irrigation fluid temperature was room temperature (22 degrees C).
      Thermometry data were acquired at 4 Hz for 5 seconds with the RF probe off, for
      20 seconds with the RF probe on, and then for 15 seconds with the RF probe off.
      During RF treatment, a 0.79-cm2 area (1.0-cm diameter) of the articular surface
      centered over the thermometry probe was treated in a paintbrush manner in
      noncontact (bRFE) or light contact (mRFE). RESULTS: Thermal chondroplasty with
      bRFE resulted in higher cartilage matrix temperatures compared with mRFE for all
      depths and regardless of fluid flow. Bipolar RFE resulted in temperatures of 95
      degrees C to 100 degrees C at 200 microm and 500 microm under the surface, with
      temperatures of 75 degrees C to 78 degrees C at 2,000 microm. Fluid flow during
      bRFE application had no effect at 200 microm. Monopolar RFE resulted in
      temperatures of 61 degrees C to 68 degrees C at 200 microm, 54 degrees C to 70
      degrees C at 500 microm under the surface, and 28 degrees C to 30 degrees C at
      2,000 microm below the surface. A significant effect of fluid flow during mRFE
      application occurred at 200 microm (NF, 61 degrees C; F, 63 degrees C) and 500
      microm (NF, 53 degrees C; F, 68 degrees C). CONCLUSIONS: In this study, we found
      significant differences between bRFE and a temperature-controlled mRFE device
      with regard to depth of thermal heating of cartilage in vitro. Bipolar RFE
      resulted in matrix temperatures high enough (>70 degrees C) to kill cells as deep
      as 2,000 microm under the articular surface. Fluid flow during thermal
      chondroplasty had the effect of significantly increasing cartilage matrix
      temperatures at 200 and 500 microm with the mRFE device. During thermal
      chondroplasty, bRFE creates greater matrix temperature elevations at equivalent
      depths and treatment duration than does mRFE. Excessive temperatures generated
      deep within the cartilage matrix could cause full-thickness chondrocyte death, in
      vivo.

PMID- 11951191
TI  - Intraoperative measurements of the subacromial distance.
AB  - PURPOSE: The purpose of this study was 2-fold: to document the accuracy of a new
      measuring device and to intraoperatively compare the subacromial distance between
      controls and patients with impingement syndrome before and after arthroscopic
      subacromial decompression (ASD). TYPE OF STUDY: Clinical study. METHODS: When
      performing an ASD, it is important that bone resection is adequate. Today the
      correct subacromial distance after bone resection is only assessed by eye,
      directly or indirectly. The subacromial distance was measured between the
      anterolateral corner of the acromion and the supraspinatus tendon in the lateral
      decubitus position. The device was inserted 2 to 3 cm below the anterolateral
      acromion. There was no subacromial pathology among the controls (n = 15, mean
      age, 28 years). In 30 patients with impingement syndrome (average age, 53 years)
      an ASD was performed. The subacromial distance was measured after bursectomy and
      then after bone resection. Intraindividual and interindividual assessment was
      performed. RESULTS: The mean value of the subacromial distance in controls was 16
      mm, the 95% confidence limits between 14 and 18 mm. The mean value in the group
      of patients with impingement syndrome was 8 mm before and 16 mm after the
      decompression. Due to the pressure within the subacromial space, the subacromial
      distance increased 1 mm. Intraindividual measurements never varied more than 1 mm
      (n = 5). The correlation coefficient between the measurements by both authors was
      0.99. CONCLUSIONS: In this study, we assessed and described the use of a
      measuring device that enables the surgeon to quantify the subacromial distance
      before and after bone resection. After bone resection, the mean value of the
      subacromial distance was well within the control values. The amount of bone
      resected varied from 5 to 13 mm. This new device enables documentation in
      clinical work as well as in research.

PMID- 11951192
TI  - Arthroscopic anatomy of the posterior ankle ligaments.
AB  - PURPOSE: Our objective was to define the arthroscopic anatomy of the posterior
      ankle ligaments. TYPE OF STUDY: Anatomic study. METHODS: Twenty fresh-frozen feet
      were dissected in order to examine the morphology of the posterior ankle
      ligaments and their variations. In addition, arthroscopic examination was
      performed in 8 feet with standard anteromedial and anterolateral portals.
      Posterior ligamentous structures were identified and marked with suture.
      Following arthroscopy, careful dissection was performed and previously marked
      anatomic structures were identified. RESULTS: At the time of anatomic dissection,
      the posteroinferior tibiofibular ligament, also called the tibial slip, was found
      to be a constant structure with varying size and shape, and well evident during
      arthroscopy due to its oblique course. The deep component of the posteroinferior
      tibiofibular ligament, also called the transverse ligament, is well defined
      during arthroscopy. The 2 ligaments not well visualized during arthroscopy are
      the superficial component of the posteroinferior tibiofibular ligament and the
      posterior talofibular ligament. CONCLUSIONS: These findings should be of interest
      in interpreting findings encountered during arthroscopic examination of ankle,
      and when a posterior soft-tissue impingement syndrome must be ruled out.

PMID- 11951193
TI  - Postoperative pain control following arthroscopic release of adhesive capsulitis:
      a short-term retrospective review study of the use of an intra-articular pain
      catheter.
AB  - PURPOSE: The purpose of this study was to examine the effectiveness of an
      arthroscopically placed intra-articular pain catheter for controlling
      postoperative pain and also review the results following arthroscopic release of
      refractor adhesive capsulitis. TYPE OF STUDY: Retrospective clinical trial.
      METHODS: Twenty-three consecutive cases (20 patients) of arthroscopic adhesive
      capsulitis release in which an intra-articular pain catheter was used were
      reviewed. Follow-up ranged from 12 to 37 months (average, 22.4 months). An intra
      articular catheter was placed under direct arthroscopic visualization from a
      superior approach into the glenohumeral joint. Postoperatively, patients were
      injected with 10 mL of 0.5% bupivacaine every 6 hours as needed. Preoperatively,
      all patients had filled out a questionnaire based on the American Shoulder and
      Elbow Surgeons (ASES) outcome guidelines and examined for range of motion.
      Postoperatively, patients were asked for their precatheter and postcatheter
      injection pain level based on the visual analog scale (1 to 10 points, 1 = no
      pain). Patients were then examined for range of motion and retested with the
      outcome questionnaire. An ASES Shoulder Score Index was calculated for each
      patient before and after the procedure. RESULTS: The average forward elevation
      preoperatively was 102 degrees and external rotation at the side was 4.5 degrees.
      At most recent follow-up, average forward elevation was 169 degrees with external
      rotation at the side 47 degrees. The Shoulder Score Index increased from an
      average of 37.1 out of 100 to 90.9 (P <.001). Before being injected with
      anesthetic through the catheter, patients had an average visual analog scale
      score of 8.1. Postinjection average pain level was 1.2 (P <.001) and all patients
      indicated that the pain catheter significantly reduced postoperative pain.
      Nineteen of 20 patients were satisfied with the procedure. CONCLUSIONS: Placement
      of an intra-articular pain catheter for delivery of bupivacaine was highly
      effective in controlling postoperative pain. In all cases, postoperative pain was
      essentially eliminated and this substantially assisted with range of motion
      exercises. Near complete restoration of range of motion without pain was achieved
      in 95% of the patients.

PMID- 11951194
TI  - Anatomic and radiographic analysis of arthroscopic tack placement into the
      superior glenoid.
AB  - PURPOSE: To anatomically and radiographically describe tack location within the
      anterosuperior (AS) and posterosuperior (PS) aspects of the glenoid when
      performing simulated repairs of type II SLAP lesions. TYPE OF STUDY: Cadaveric
      anatomic and radiographic analysis. METHODS: Arthroscopy was performed on 7 fresh
      frozen cadaveric shoulders and bioabsorbable tacks were placed in the AS and PS
      aspects of the glenoid to simulate repair of a type II SLAP lesion. The PS tack
      was placed through an accessory portal 1 cm lateral and 1 cm anterior to the
      posterolateral corner of the acromion. Dissection was then performed, and the
      incision made in the rotator cuff when creating the posterolateral accessory
      portal (PLAP) was identified and measured. Tack location within the glenoid was
      visually studied after removal of all soft tissues and recorded as being either
      completely within bone or partially within bone. The tacks were recannulated with
      guide pins and 3 radiographs were then taken of each specimen (true
      anteroposterior, axillary, and en face glenoid views) and angles of entry
      determined. In addition, the angle of deviation from the orthogonal at the point
      of entry of each tack was measured on the en face glenoid view. RESULTS: The
      average incision made in the rotator cuff for creation of the PLAP measured 10.3
      mm in maximum diameter. In 6 of 7 specimens, this incision was made through
      muscle and not tendon. Seven of 7 AS tacks were completely within bone, and only
      5 of 7 PS tacks remained completely within bone. On the true anteroposterior
      view, the average angle of entry from the vertical for the AS tack was 64
      degrees. For the PS tack, this angle measured 86 degrees. On the axillary view,
      the angle of placement from the coronal averaged 22 degrees for the AS tack and
      42 degrees for the PS tack. For the en face glenoid view, the angle of entry from
      the vertical was 34 degrees for the AS tack and 93 degrees for the PS tack.
      Lastly, the angle of deviation from the orthogonal on the en face glenoid view
      was 12 degrees and 35 degrees for the AS and PS tacks, respectively. This
      difference was statistically significant at P <.001. CONCLUSIONS: This study
      provides quantitative data on the angle of placement and location of tacks within
      the superior glenoid when performing repairs of type II SLAP lesions. It also
      shows the PLAP to be a safe portal for the placement of devices into the
      posterosuperior aspect of the glenoid. Furthermore, the data show the AS tack to
      be more reliably placed than the PS tack.

PMID- 11951195
TI  - The trans-rotator cuff approach to SLAP lesions: technical aspects for repair and
      a clinical follow-up of 31 patients at a minimum of 2 years.
AB  - PURPOSE: To discuss a new technique for the surgical treatment of type II SLAP
      lesions as well as the evaluation of the technique's effectiveness with a minimum
      2-year follow-up. TYPE OF STUDY: Retrospective clinical follow-up study. METHODS:
      We present a clinical follow-up of 31 patients who were treated arthroscopically
      for type II SLAP lesions using a trans-rotator cuff portal at an average follow
      up time of 3.7 years. Patients were screened for concomitant procedures including
      rotator cuff repairs, shoulder stabilizations, thermal capsullographies, and
      previous surgeries. These patients were subsequently excluded from the study.
      Patients were given a standard physical examination of the upper extremity at our
      institution and they completed both the L'Isalata and American Shoulder and Elbow
      Surgeons questionnaires. RESULTS: All 31 patients identified were available for
      follow-up at an average time of 3.7 years postoperatively (range, 2.0 to 7.4
      years). The average L'Insalata score was 87.0 points (range, 46.1-100 points);
      the average ASES score was 87.2 points (range, 46.7-100 points). The average pain
      score was 1.5 (range, 0-5) and only 4 of the 31 patients complained of moderate
      pain with activity. Sixteen of the 31 patients returned to their preinjury level
      of sports; 11 of the 31 patients returned to limited activity and 2 patients were
      inactive at the time of follow-up. Overall satisfaction with the procedure
      averaged 3.79 points (range, 0-5 points): 22 patients rated overall satisfaction
      as good or excellent, 6 patients reported a fair outcome, and only 3 patients
      were unsatisfied with the results of the surgery. One patient who was unsatisfied
      with the procedure had reinjured his superior labrum and required a second
      operation. None of the 31 patients had symptoms suggestive of rotator cuff
      pathology. Of the 30 patients found to have a positive Active Compression test
      preoperatively, 26 of these patients now had a negative sign. CONCLUSIONS: The
      trans-rotator cuff approach allows for a more optimal placement of a
      biodegradable fixation device and/or suture anchors into the superior labrum.
      Furthermore, we believe that this approach does not compromise the function of
      the rotator cuff. The trans-rotator cuff technique is an effective and safe
      modality to address superior labral pathology.

PMID- 11951196
TI  - Arthroscopic versus conservative treatment of osteochondritis dissecans of the
      knee: value of magnetic resonance imaging in therapy planning and follow-up.
AB  - PURPOSE: Magnetic resonance imaging (MRI) was used to control the short-term
      outcome of osteochondritis dissecans (OCD) of the femoral condyle depending on
      conservative or surgical treatment at the beginning of therapy. TYPE OF STUDY:
      Case series. METHODS: Treatment planning for OCD depended on the stage on MRI
      when analyzing the appearance of the interface between parent bone and fragment
      on T1- and T2-weighted images. Twenty-seven patients received conservative
      treatment and 46 patients underwent arthroscopic surgery. After 20 to 24 months,
      patients were re-evaluated by MRI to assess the condition of bony fragment,
      parent bone, and interface so as to determine partial or complete remission, no
      change, or progression of OCD. RESULTS: After conservative treatment, MRI showed
      partial or complete remission in 30% of patients and no change in 63%.
      Arthroscopic treatment led to remission in 37% and to no change in 57%.
      Progressive disintegration of OCD was found on MRI in 7% of conservatively
      treated patients and in 7% of the surgery patients. In 33.3% of the patients
      initially treated conservatively, it was decided to treat them arthroscopically
      because of ongoing, unacceptable clinical symptoms. CONCLUSIONS: The rates of
      remission and progression were not significantly different between the groups.
      The patients' age was significantly correlated to the rate of consolidation. OCD
      in juveniles under 16 years of age followed a milder course than in adults.

PMID- 11951197
TI  - Arthroscopic all-inside meniscus repair using a new refixation device: a
      prospective study.
AB  - PURPOSE: To evaluate complications and clinical results after meniscus refixation
      using a new all-inside technique. TYPE OF STUDY: Prospective clinical study.
      METHODS: This study reports clinical results of 37 patients after refixation of
      an unstable bucket-handle meniscus tear using a new all-inside technique (Mitek
      Meniscal Repair System; Mitek, Ethicon, Norderstedt, Germany). Twenty tears were
      located in the peripheral third (red zone) and 17 in the middle third (red/white
      zone). The average operating time of meniscus refixation was 29.4 minutes. In 17
      patients, a reconstruction of the anterior cruciate ligament (ACL) was performed
      6 to 8 weeks after the refixation. All patients (aged 15 to 48 years) were re
      examined after a minimum follow-up of 12 months. RESULTS: In the ACL group (n =
      17) we examined the menisci arthroscopically at surgery. All menisci were still
      in the reduced position and they were stable to probing. In 12 cases, the anchors
      were not visible at arthroscopy; in 7 cases, the vertical bar was lying just
      beyond the femoral meniscus surface. In 1 case, we observed superficial damage of
      the femoral cartilage in the corresponding area. One patient developed
      superficial posteromedial knee pain after 4 weeks due migration of a staple into
      the subcutaneous fat tissue. There were 5 reruptures during the first
      postoperative year. Two patients reported an adequate trauma, but all had tears
      in the middle one third of the meniscus (red/white zone). At the 1-year follow
      up, none of the remaining 32 patients had clinical symptoms indicating a
      rerupture such as blocking, medial joint pain, or positive meniscus signs. No
      patient had an effusion or local swelling. The average pretraumatic Lysholm score
      decreased from 95 to 91 points. The Tegner activity score decreased from 4.9
      (pretrauma) to 3.6 (postoperatively). CONCLUSIONS: Short-term clinical results
      using an all-inside meniscus repair system seem to be promising. However, a
      longer follow-up is needed.

PMID- 11951198
TI  - The effect of axial tibial torque on the function of the anterior cruciate
      ligament: a biomechanical study of a simulated pivot shift test.
AB  - PURPOSE: Various techniques are used to produce the pivot shift phenomenon after
      anterior cruciate ligament (ACL) injury. In particular, the amount of applied
      axial tibial torque varies among examiners. Thus, the objective of this study was
      to determine the effect of the magnitude and direction of axial tibial torque in
      combination with valgus torque on the resulting knee kinematics during such a
      simulated pivot shift test. TYPE OF STUDY: This was a biomechanical study that
      used cadaveric knees with the intact knee of the same specimen serving as a
      control. METHODS: On 19 human cadaveric knees (age, 26 to 69 years), a constant
      10-Nm valgus torque was applied at 15 degrees of knee flexion. Then, internal and
      external tibial torque was applied incrementally from 0 to 10 Nm and the
      resulting kinematics of the ACL-intact and ACL-deficient knee, as well as the in
      situ force in the ACL, were measured using a robotic/universal force-moment
      sensor testing system. RESULTS: In response to isolated valgus torque, the
      coupled anterior tibial translation for the ACL-intact and ACL-deficient knee was
      1.6 +/- 2.4 mm and 8.5 +/- 4.7 mm, respectively; therefore the difference between
      the ACL-intact and ACL-deficient knee was 6.9 +/- 3.4 mm. With an external tibial
      torque greater than 5 Nm, the tibia translated up to 4 mm posteriorly for both
      the ACL-intact and ACL-deficient knee. Whereas, internal tibial torque greater
      than 1.6 Nm caused a rapid increase in coupled anterior tibial translation up to
      10.2 mm in the ACL-deficient knee, while causing only a gradual increase for the
      ACL-intact knee. With excessive internal torque of 10 Nm, the difference in
      coupled anterior tibial translation was only 4.4 +/- 2.2 mm, suggesting a
      decrease in the sensitivity of the test. Correspondingly, the in situ force in
      the ACL under 10 Nm valgus tibial torque was 43 +/- 17 N, and increased up to 87
      +/- 32 N as a 10-Nm internal torque was added. By applying a 3.3-Nm external
      tibial torque in addition to the 10-Nm valgus torque, the in situ force decreased
      to 21 +/- 14 N. CONCLUSIONS: This study showed that a minimal amount of internal
      torque in combination with valgus torque may be a suitable way to elicit a pivot
      shift from an ACL-deficient knee.

PMID- 11951199
TI  - Lateral release for patellofemoral arthritis.
AB  - PURPOSE: To determine the outcome of treatment of patients with symptomatic
      patellofemoral osteoarthritis by closed lateral patellar retinacular release.
      TYPE OF STUDY: Retrospective study. METHODS: Fifty patients who underwent 53
      lateral retinacular release procedures between 1995 and 1999 for the treatment of
      symptomatic patellofemoral arthritis were assessed by questionnaire comprising
      the Oxford knee score, a visual analogue scale (VAS, 0-10) for pain, and
      questions relating to level of patient satisfaction. Patients were included in
      this study whether or not tibiofemoral arthritis was present, but lateral release
      was performed only in those for whom the anterior knee pain of patellofemoral
      arthritis appeared to predominate. RESULTS: The average patient age was 53 years
      (range, 27 to 79 years). There were 14 men (28%) and 36 women (72%). Follow-up
      was a mean of 31 months (range, 12 to 65 months). Four patients underwent total
      knee replacement at 7, 14, 16, and 18 months after lateral release for recurrence
      of symptoms. In the remaining 49 knees, mean pain VAS was 3.8 +/- 2.8. In 39
      knees (80%), patients judged that they had experienced a reduction in pain
      compared with their preoperative state (2 were pain free), 8 (16%) were
      unchanged, and 2 (4%) were worse. The average Oxford knee score was 27 (range, 12
      48). At follow-up, 33% of patients were very satisfied, 26% satisfied, and 41%
      dissatisfied with their knee. The presence of tibiofemoral disease did not affect
      any of the outcome measures. Two patients developed superficial infections of the
      arthroscopic port sites. There were no cases of hemarthrosis. CONCLUSIONS:
      Arthroscopic lateral release is effective in reducing the pain of symptomatic
      patellofemoral osteoarthritis and gives reasonable rates of patient satisfaction
      irrespective of the presence of tibiofemoral arthritis.

PMID- 11951200
TI  - Vastus lateralis release for painful bipartite patella.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of vastus
      lateralis release for painful bipartite patella. We have also compared the
      results of open method versus arthroscopic method using a holmium:YAG laser
      system (OmniPulse Holmium Laser System; Trimedyne Inc, Irvine, CA). TYPE OF
      STUDY: This study was a nonrandomized control and cross-over trial. METHODS:
      Fifteen patients with 17 painful bipartite patella who underwent vastus lateralis
      release were included in this study. The average age of patients was 14.3 +/- 2.2
      years. In 7 knees of 6 patients, vastus lateralis release was performed through a
      skin incision over the bipartite fragment, and in 10 knees of 9 patients, we
      performed the procedure arthroscopically with the holmium:YAG laser. We assessed
      clinical and radiographic data of the patients chronologically in both groups.
      RESULTS: In all patients, pain over the fragment disappeared within 4 weeks after
      the operation, and all returned to their previous sports activities at an average
      of 3.1 +/- 0.9 months postoperatively. Clinical assessment was classified as
      excellent in 13 knees and good in 4 knees. Bone union at 6 months after the
      operation was complete in 11 knees (64.7%) and incomplete in 6 knees (35.3%), and
      none of the knees was graded as not healed. Bone union in patients with an age of
      15 or younger was significantly better than that in patients over 15 years of age
      (P <.05). Release under arthroscopy showed statistically better results in
      duration of knee effusion (P <.05), return of circumference of thigh (P <.05),
      and return of muscle strength (P <.05). CONCLUSIONS: Because vastus lateralis
      release is less invasive surgery with good results, we conclude that this
      procedure can be a first choice of operative treatment for painful bipartite
      patella.

PMID- 11951201
TI  - Arthroscopic assessment of occult intra-articular injury in acute ankle
      fractures.
AB  - PURPOSE: To arthroscopically assess the pattern and extent of intra-articular
      damage associated with ankle fractures. TYPE OF STUDY: Prospective case series.
      METHODS: From 1989 to 1998, 48 consecutive patients with acute unstable ankle
      fractures underwent ankle arthroscopy followed by reduction and internal
      fixation. In addition, all injuries were categorized by specific osseous,
      ligamentous, and articular pathology, based on clinical and arthroscopic
      examination. Whenever possible, the fractures were classified according to Lauge
      Hansen and Danis-Weber schemes. RESULTS: Traumatic articular surface lesions
      (TASLs), including chondral defects and osteochondral lesions measuring greater
      than 5 mm in diameter, were identified in 30 of the 48 ankles (63%), with 11
      lesions localized to the tibia and 19 noted on the talus. The tibial lesions were
      at the posterior syndesmotic ligament insertion in 6 cases, at the anterior
      capsule origin in 3 cases, and at the central articular surface in 2 cases. Of
      the 19 talar lesions, 15 involved the medial dome and 4 involved the lateral
      articulation. TASLs of the talus in this series were uniformly unstable or
      displaced and virtually devoid of subchondral bone, precluding satisfactory
      internal fixation. Of the 10 pronation-external rotation fractures, 7 had
      articular surface defects with 5 involving the medial and 2 the lateral dome. Ten
      of the 24 supination-external rotation or Danis-Weber B fractures were found to
      have TASLs of the talus, 9 medial and 1 lateral. Nine of 12 fractures with
      syndesmosis disruptions sustained full-thickness damage to the talar chondral
      surface (P =.01). CONCLUSIONS: Ankle fractures have a high incidence of
      concomitant intra-articular pathology with syndesmosis disruption portending a
      particularly high risk of articular surface injury to the talar dome. Arthroscopy
      is a valuable tool in identifying and treating intra-articular damage that would
      otherwise remain unrecognized and may provide prognostic information regarding
      the functional outcome of these injuries.

PMID- 11951202
TI  - Arthroscopic treatment of capitellum fracture of the humerus.
AB  - This case report presents a type I Hahn-Steinthal capitellum fracture treated by
      screw fixation under arthroscopic control. It is the first published case of the
      use of this technique. The 3 types of capitellum fractures and different methods
      for treatment are described: functional treatment, open surgery, and arthroscopic
      surgery. The arthroscopic approach allows a precise reduction and fixation of the
      articular fragment with a better evaluation of associated lesions compared with
      the open surgery. Arthroscopic fixation minimizes the damage to periarticular
      soft tissues and has a lower morbidity compared with open surgery.

PMID- 11951203
TI  - Arthroscopically assisted reduction and fixation of a juvenile Tillaux fracture.
AB  - This is the first report of arthroscopically assisted reduction and fixation of a
      juvenile Tillaux fracture. Arthroscopic visualization assisted with the anatomic
      reduction of the articular fragment. This adds arthroscopy as a modality
      available to help obtain accurate reduction as well as understand the nature of
      the fracture pattern in juvenile Tillaux fractures along with its adult
      counterpart and other intra-articular fractures.

PMID- 11951204
TI  - Treatment of chondroblastoma of the calcaneus with a secondary aneurysmal bone
      cyst using endoscopic curettage without bone grafting.
AB  - Chondroblastoma is a relatively rare benign bone tumor. Approximately 7% of
      chondroblastomas occur in the calcaneus, and 17% of chondroblastoma associated
      with cystic lesions. We report a case of a chondroblastoma in the calcaneus with
      a secondary aneurysmal bone cyst treated successfully by endoscopic curettage
      without bone grafting. New bone formation is facilitated by minimal damage to the
      bone and soft tissue. The cosmetic results of this procedure are good. Two years
      later, the patient is asymptomatic with no radiographic evidence of recurrence.
      Endoscopic curettage without bone grafting is a promising new treatment for
      chondroblastoma.

PMID- 11951205
TI  - Arthroscopic rotator interval repair and anterior portal closure: an alternative
      technique.
AB  - The rotator interval capsule has been implicated as an important restraint to
      shoulder subluxation, and plays an important role in shoulder stability. Anterior
      portal placement during arthroscopic shoulder instability repair violates the
      interval capsule and compromises the biomechanical integrity of the rotator
      interval. The following is a technique for interval capsule repair. Using an 18
      gauge needle via the anterior portal, a monofilament suture is passed through the
      capsule just above the subscapularis. A Penetrator suture retriever (Arthrex,
      Naples, FL) is passed high into the capsule just anterior to the biceps. The
      intra-articular end of the suture is then removed from the superior aspect of the
      interval capsule. The suture limbs are then tied into the portal onto the
      anterior capsule. The technique is advantageous because it may be repeated as
      needed until appropriate interval plication has been achieved. Furthermore, it
      does not require an interval portal through which to pass the suture. It appears
      to be a safe, effective, and reproducible technique for arthroscopic rotator
      interval closure.

PMID- 11951206
TI  - The joint jack: report of a new technique essential for elbow arthroscopy.
AB  - Visualization and access are of fundamental importance in arthroscopy, including
      arthroscopy of the elbow. A new technique not previously described in the
      literature improves both of these factors for key areas within the elbow that
      would otherwise be inaccessible. This technique employs the application of gentle
      leverage to pry apart the surfaces of the ulnohumeral articulation when viewing
      and working posteriorly to improve visualization and access to the ulnohumeral
      and radiocapitellar articular spaces. We believe this technique is essential for
      full arthroscopic viewing of the intra-articular regions of the ulnohumeral and
      radiocapitellar joints.

PMID- 11951207
TI  - A water-infusion system with two reservoirs at different levels.
AB  - To provide a continuous supply of fluid during arthroscopic surgery, we suggest
      an infusion system with 2 reservoirs placed at different heights. The lower bag
      serves as a water reservoir, which allows more time for the circulating nurse to
      complete the task of exchanging the emptied water bag.

PMID- 11951208
TI  - Surgical treatment of liver metastases.
AB  - Approximately 50% to 60% of patients with colorectal cancer will develop hepatic
      metastases during the course of their illness, with 20% to 30% of patients having
      liver metastases at time of diagnosis. In nearly a quarter of these patients the
      liver is the only site of disease. Surgical resection of isolated hepatic
      metastases has been associated with a 27% to 37% 5-year survival and confers a
      survival advantage compared to patients not undergoing resection. Thorough
      preoperative and intraoperative evaluation is necessary to select appropriate
      surgical candidates who may benefit from resection. This article examines
      criteria useful in patient selection, and also reviews the management of
      recurrent hepatic metastases and the role of repeat hepatic resection.

PMID- 11951209
TI  - Intrahepatic arterial infusion of chemotherapy: pharmacologic principles.
AB  - Hepatic arterial (HA) infusional chemotherapy possesses a number of constraints
      not found with systemic chemotherapy. The drug used should have activity in a
      dose-responsive way without significant hepatic toxicity. The drug must also
      possess suitable pharmacokinetic properties, namely, a high total body clearance
      and hepatic extraction, so as to generate high hepatic and low systemic
      exposures. Of the drugs examined for HA use, 5-fluoro-2'-deoxyuridine (FUDR,
      floxuridine) demonstrates the best properties. In HA infusional therapy, the
      catheter is positioned to deliver drug directly to the liver only and must be
      connected to a reliable pumping mechanism. Surgical implantation of catheters and
      pumps provides a safe and reliable means to infuse HA FUDR. HA FUDR delivery via
      an implanted system in the treatment of colorectal liver metastases represents
      the largest application of HA therapy and provides a basis for future advances
      when combined with other regional and systemic treatments.

PMID- 11951211
TI  - Transarterial perfusion of liver metastases.
AB  - Progressive growth of unresectable metastatic or primary malignancies confined to
      the liver is a significant clinical problem. Approximately 25% of patients with
      colorectal cancer will develop metastatic disease exclusively or largely confined
      to liver, the vast majority of which are not amenable to surgical resection.
      Despite aggressive systemic or regional chemotherapy, survival is only 12 to 18
      months. More than 80% of patients with ocular melanoma develop liver metastases
      as the first site of recurrent disease, and death from hepatic disease
      progression typically occurs 2 to 7 months after diagnosis. In addition, the
      liver is also the preferred site of metastatic disease for gastrointestinal or
      pancreatic neuroendocrine tumors. A number of physiological and anatomic features
      of the liver make it an ideal organ for regionally directed therapy to allow dose
      intensification to the cancer-burdened area while reducing or eliminating
      unnecessary systemic toxicity. To that end, complete vascular isolation and
      perfusion of the liver using a recirculating extracorporeal circuit, also called
      isolated hepatic perfusion (IHP), has been under clinical evaluation at our
      institution and others. In this article, we review the current results with IHP
      and its potential utility in the treatment of patients with unresectable hepatic
      malignancies.

PMID- 11951210
TI  - Intrahepatic arterial infusion of chemotherapy: clinical results.
AB  - Approximately 60% of patients diagnosed with colorectal cancer (CRC) will go on
      to develop hepatic metastases. Although surgical resection is the only curative
      modality, a majority will not be able to undergo surgery. Alternative methods for
      treating this population have focused on the feasibility of hepatic arterial
      infusion (HAI) of chemotherapy. Randomized data in this field have been hampered
      due to small numbers of patients in some trials, or crossover between groups.
      However, most trials have suggested an improvement in both overall and
      progression-free survival with HAI therapy. Dose-limiting toxicity associated
      with HAI is related to hepatobiliary sclerosis, which has been reduced with the
      use of dexamethasone as part of the treatment. Current research is underway to
      improve the rate of extrahepatic metastases in patients undergoing HAI.

PMID- 11951212
TI  - Hepatic artery chemoembolization.
AB  - Chemoembolization is a technique that can deliver high concentrations of
      therapeutic agents directly to the liver for prolonged periods. Considerable
      experience has been gained in the treatment of hepatocellular carcinoma, where it
      appears to be a safe procedure that provides survival advantage over conservative
      therapy. There is much less experience in the treatment of hepatic metastases.
      Patients with carcinoid, pancreatic islet cell tumor, and sarcoma metastatic to
      the liver do appear to benefit from chemoembolization. Efficacy in other groups,
      such as patients with colorectal cancer metastatic to the liver, is less well
      established, but a recently initiated multicenter trial may resolve this issue.

PMID- 11951214
TI  - Locoregional immuno(bio)therapy for liver metastases.
AB  - Despite advances in locoregional chemotherapy, treatment of metastatic liver
      tumors remains a challenge. Since the liver is the largest organ of the
      reticuloendothelial system, locoregional immunotherapy would be a reasonable
      approach for the management of hepatic metastases. Indeed, various immunological
      approaches have been explored. Regional infusion of cytokines such as interleukin
      2 (IL-2) or tumor necrosis factor-alpha (TNF-alpha) through the hepatic artery or
      the portal vein has been combined with chemotherapy and demonstrated to be better
      than chemotherapy alone. Locoregional adaptive immunotherapy (AIT) using
      lymphokine-activated killer (LAK) cells or tumor-infiltrating lymphocytes (TIL)
      has also been tried with rather disappointing responses. Addition of
      immunostimulants such as OK-432 to AIT increased clinical responses. Recently,
      several new approaches have emerged to improve the outcome of locoregional
      immunotherapy. Embolization of melanoma metastatic to the liver with a
      granulocyte-macrophage colony-stimulating factor (GM-CSF)/ethiodized oil emulsion
      resulted in control of liver metastases, as well as development of significant
      immune responses in remote extrahepatic metastases. A gene therapy designed to
      introduce foreign major histocompatibility complex (MHC) molecules in colorectal
      metastases has proven to be a safe and feasible approach. Larger scale clinical
      trials are mandatory to define the role of locoregional immunotherapy for
      metastatic tumors in the liver.

PMID- 11951213
TI  - Radioembolization for hepatic metastases.
AB  - In a phase I/II study, 37 patients with metastatic liver disease, predominantly
      from colorectal cancer (n = 33) were treated between 1986 and 1994 by
      intrahepatic arterial embolization of radioactive yttrium 90 (Y 90) glass
      microspheres. The calculated total liver dose increased in stages from 5,000 cGy
      to 15,000 cGy. Mean follow-up was 8 months (range, 1 to 49). No major procedural,
      hematologic, or pulmonary complications occurred. Late gastroduodenal ulceration
      occurred early in the study at 6 to 8 weeks in three patients with a history of
      chronic alcohol abuse and was treated successfully medically. Of 30 patients with
      either computed tomography (CT) or sonography follow-up for 4 months or longer,
      15 had tumor involvement in the liver that was diffuse, irregular, or
      infiltrating with mixed or poor vascularity and thus definitive imaging changes
      could not be appreciated on follow-up. In 15 patients with identifiable marker
      lesions with developed hypervascularity, post-treatment beneficial effects were
      noted. In seven of these patients followed by CT, decreased tumor attenuation and
      sharper definition of tumor-liver interface were noted. Findings on sonography in
      eight patients were increased tumor sonolucency centrally, consistent with
      liquefaction necrosis, and rim hyperechogenicity, consistent with calcification.
      A 25% to 40% decrease in area of marker lesions occurred in five patients and one
      other patient had small 1.0- to 1.5-cm lesions disappear temporarily on
      sonography. In conclusion, this method provides a feasible single-session
      technique for treatment of hepatic metastases. Complications are low and if the
      tumor pattern is nodular with some hypervascularity, beneficial effects are
      observed clinically and on imaging studies.

PMID- 11951215
TI  - Radiofrequency ablation of hepatic metastases.
AB  - The liver is one of the most common sites for cancer metastases that result in
      significant morbidity and mortality. Although surgical resection is associated
      with improvements in local control and survival, only a minority of patients are
      candidates for this approach. Radiofrequency ablation (RFA) is an important
      alternative/complementary tool in the treatment of metastatic disease to the
      liver and can lead to palliation as well as increased survival in selected
      patients. RFA has been shown to be safer and better tolerated than other ablative
      techniques and has been associated with a low rate of local recurrence when
      performed properly. RFA also has shown some promise in combination with surgical
      resection and other therapies. Patients who undergo RFA still suffer from
      progressive metastatic disease, reinforcing the premise that local therapies have
      little impact on the natural history of aggressive cancers. Trials combining RFA
      with surgical resection and regional and systemic chemotherapy are ongoing and it
      is the hope that RFA combined with multimodality adjuvant therapy will reduce the
      development of both local disease and progressive metastatic disease, leading to
      improved overall survival.

PMID- 11951216
TI  - Cryotherapy in the treatment of liver metastases from colorectal cancer.
AB  - Although hepatic resection remains the treatment of choice for metastatic disease
      to the liver from colorectal cancer, the procedure is only possible for
      approximately 10% of patients. Ninety percent of patients with liver metastases
      ultimately die of liver failure. Thus, attention has turned to other,
      locoregional techniques that may be used alone or in conjunction with resection
      to increase the eligibility for some type of surgical, potentially curative
      treatment. One such option is cryotherapy. This review provides technical,
      physiologic, and outcome information regarding this technique. Semin Oncol 29:183
      191.

PMID- 11951217
TI  - Percutaneous alcohol ablation for liver metastasis.
AB  - Ultrasound-guided percutaneous alcohol injection (PAI) is used in the treatment
      of hepatocellular carcinoma for lesions less than 3 to 5 cm in diameter. However,
      few studies in the literature have evaluated the place of PAI in the treatment of
      liver metastasis. Alcohol acts by causing coagulative necrosis, followed by the
      formation of fibrotic and granulomatous tissue and thrombosis of small vessels.
      The results of the various published studies are similar, with a complete
      necrosis rate lower than that obtained in hepatocellular carcinoma. Nevertheless,
      in more than 50% of cases of liver metastasis less than 4 cm in diameter,
      complete necrosis can be obtained, and PAI would seem to be a reasonable option
      for the treatment of small metastases of colorectal or mammary origin and for
      endocrine tumors when surgery is contraindicated. PAI could be a valuable
      alternative in the treatment of selected small metastases of the liver. However,
      the new techniques of local tumor destruction (interstitial laser
      photocoagulation (ILP), cryoablation, radiofrequency thermal ablation, and
      microwave destruction) will replace PAI for the treatment of liver metastasis in
      the near future.

PMID- 11951218
TI  - External-beam radiotherapy in the management of liver metastases.
AB  - This review discusses the importance of palliation of liver metastases. Although
      colorectal cancer comprises the majority of patients with metastatic liver
      disease, a number of other malignancies can be involved. Palliation of metastatic
      disease to liver has generally not included the use of external-beam radiotherapy
      because of restricted liver tolerance to radiotherapy. However, more recently,
      treatment policies have evolved to more generous use of palliative radiotherapy
      with utilization of tumor boost doses to partial liver volumes. This has resulted
      in improvement in palliation and a suggestion of improved survival with higher
      radiotherapy doses, which have been well tolerated by small volumes of liver.

PMID- 11951219
TI  - Gene therapy for liver metastases.
AB  - Although resection is currently the only curative approach for metastatic liver
      cancer, only a small number of cases are suitable for this procedure. In the past
      few years, gene therapy has emerged as an appealing treatment option for liver
      cancer. Phase I and II clinical trials have been conducted in patients with
      either primary or secondary liver cancer using a variety of genes including tumor
      suppressor gene p53, suicide genes, immune genes, and replication-competent
      oncolytic adenoviruses. The results have shown that, although gene therapy has
      been well tolerated and toxicity has been low, the clinical benefit has so far
      been marginal. Gene therapy as a definitive treatment for liver metastases
      remains limited, at least for the time being, but it may be useful as an adjuvant
      treatment in combination with radiotherapy, chemotherapy, and/or surgery to
      achieve disease-free survival.

PMID- 11951220
TI  - The use of the Naugle orbitometer in maxillofacial trauma.
AB  - BACKGROUND AND OBJECTIVES: Objective measuring of globe position is not a
      universal practice in the management of orbital trauma. Few studies in the
      literature advocate its routine use. METHODS AND MATERIALS: The Hertel
      exophthalmometer is the most widely used instrument; however, in trauma involving
      the lateral orbital rim (e.g., in zygoma fractures), the results are inaccurate
      because the displacement of the zygomatic bone interferes with its reference
      point on the lateral orbital rim. A more recent measuring device, the Naugle
      orbitometer, was introduced in 1992. It uses the superior orbital rim (frontal
      bar) and inferior orbital rim (malar eminence) as reference points. RESULTS
      AND/OR CONCLUSIONS: This article reports experience with this instrument in
      objective measuring the position of the globe in orbital trauma. These
      measurements are used 1) to monitor fractures that may not require repair but
      should be followed and observed for dystopia or enophthalmos, 2) to determine the
      adequacy of fracture repair, and 3) to determine the volume adjustment required
      for correcting enophthalmos. Future studies will be directed to compare the
      accuracy of Naugle and Hertel exophthalmometers.

PMID- 11951221
TI  - Nasoethmoid orbital fractures: diagnosis and management.
AB  - BACKGROUND AND OBJECTIVES: Trauma to the central midface may result in complex
      nasoethmoid orbital fractures. Due to the intricate anatomy of the region, these
      challenging fractures may often be misdiagnosed or inadequately treated. The
      purpose of this article is to aid in determining the appropriate exposure and
      method of fixation. METHODS AND MATERIALS: This article presents an organized
      approach to the management of nasoethmoid orbital fractures that emphasizes early
      diagnosis and identifies the extent and type of fracture pattern. It reviews the
      anatomy and diagnostic procedures and presents a classification system. The
      diagnosis of a nasoethmoid orbital fracture is confirmed by physical examination
      and CT scans. Fractures without any movement on examination or displacement of
      the NOE complex on the CT scan do not require surgical repair. Four clinical
      cases serve to illustrate the surgical management of nasoethmoid fractures.
      RESULTS AND/OR CONCLUSIONS: Early treatment using aggressive techniques of
      craniofacial surgery, including reduction of the soft tissue in the medial
      canthal area and restoration of normal nasal contour, will optimize results and
      minimize the late post-traumatic deformity. A high index of suspicion in all
      patients with midfacial trauma avoids delays in diagnosis.

PMID- 11951222
TI  - Surgical management of the facial nerve in craniofacial trauma and long-standing
      facial paralysis: cadaver study and clinical presentations.
AB  - BACKGROUND AND OBJECTIVES: Examination of the extratemporal branches of the
      facial nerve reveals several branching patterns of the facial nerve, indicating
      the variability in the course of the nerve. Due to such variance, injury to this
      nerve often accompanies facial trauma and surgical dissection for the repair of
      facial bone injuries, and it may result in high morbidity. METHODS AND MATERIALS:
      A study of 12 fresh cadavers was performed to 1) review the variability in
      location of the extratemporal branches of the facial nerve, 2) identify the soft
      tissue injuries in which the facial nerve is at risk, and 3) discuss surgical
      options for repair. The authors identified the zygomatic and buccal and the
      extratemporal branches of the facial nerve. Among the five extratemporal
      branches, there is a significant crossover between all, except the temporal and
      the mandibular branches. This indicates that dissection should proceed with great
      caution, since injury to the temporal and marginal mandibular branches is
      unlikely to resolve spontaneously. The management of injuries within one year and
      those of longer duration is discussed. RESULTS AND/OR CONCLUSIONS: Two of the 5
      major branches of the extratemporal facial nerve have a high morbidity following
      injury. Repair should be performed within the first 72 hours. Graft, if required,
      should be placed in 9 to 12 months.

PMID- 11951224
TI  - Case report: repair of traumatic oronasal fistula using hydroxyapatite cement: a
      preliminary case report.

PMID- 11951223
TI  - Posttraumatic carotid-cavernous sinus fistula.
AB  - BACKGROUND AND OBJECTIVES: Posttraumatic carotid-cavernous sinus fistula is a
      rare complication of maxillofacial trauma and is seldom discussed in the
      literature. Motor vehicle accidents, falls, and other crush injuries contribute
      to the incidence of basilar skull fractures and the formation of fistulae. When
      injuries occur in the vessel wall, the carotid artery has the potential to fill
      the low-pressure cavernous sinus. The symptoms include chemosis, proptosis,
      pulsating exophthalmos, diplopia, ophthalmoplegia, orbital pain, audible bruits,
      and blindness. METHODS AND MATERIALS: The conventional treatments include carotid
      ligation and embolization. These techniques have often proved to be ineffective.
      A new method--the occlusive balloon technique--has been developed and is
      described in this article. A clinical case is used to illustrate the procedure.
      RESULTS AND/OR CONCLUSIONS: Utilization of balloon catheters provides a minimally
      invasive technique to treat patients, without significant morbidity or mortality.
      The procedure is found to be successful and predictable.

PMID- 11951225
TI  - Hydroxyapatite cement in craniofacial trauma surgery: indications and early
      experience.
AB  - BACKGROUND AND OBJECTIVES: Reconstruction of the nonstress-bearing portions of
      the craniofacial skeleton has recently utilized several alloplastic compounds.
      One such recent compound is hydroxyapatite cement (HAC)--a calcium-phosphate
      based product. Its chemical structure consists primarily of calcium phosphate, as
      does human bone, and this similarity in the mineral structure renders it
      biocompatible. METHODS AND MATERIALS: Based on clinical indications for HAC, the
      authors have classified acquired craniofacial defects into four types. This
      article presents 5 clinical cases with craniofacial fractures, sustained in
      various accidents, in which hydroxyapatite cement was used to prevent cranial
      deformities or to reinstate contour. RESULTS AND/OR CONCLUSIONS: Complications
      were encountered in some of these cases, but all patients healed without any
      secondary complications. While the short-term experience using hydroxyapatite
      cement in craniofacial trauma surgery has been favorable, long-term studies in
      humans are required to validate the safety and efficacy of this product.

PMID- 11951226
TI  - Indications for treatment of subcondylar mandibular fractures.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to establish a reliable
      criteria for implementation of either an open surgical or a closed conservative
      treatment of subcondylar fractures, based on clinical data and analytical
      mathematical model. METHODS AND MATERIALS: A total of 512 subcondylar fractures
      were treated during a 3-year period. Of these, 256 were fractures characterized
      by either displacement or dislocation of the proximal (condylar) segment.
      Patients were treated with open reduction and internal fixation (ORIF) or closed
      reduction (CR) techniques. Patients were evaluated pre- and postoperatively by
      clinical examination, 3-dimensional axiography, radiographic imaging, and
      ultrasonography. A mathematical model was developed for estimating the loss of
      vertical ramus height. RESULTS AND/OR CONCLUSIONS: When the displacements were
      less than 37 degrees from the sagittal axis of the ascending ramus, the ensuing
      loss of vertical height was negligible when fractures were treated by
      conservative techniques. When the displacements exceeded 37 degrees, the
      fractures resulted in a significant decrease of vertical ramus height. Based on
      these data, 37 degrees appears to be the point for decision of whether to use
      closed or open treatment.

PMID- 11951227
TI  - Treatment of traumatic mandibular nonunion.
AB  - BACKGROUND AND OBJECTIVES: Nonunion is a complication in mandibular fractures.
      The causative factors include delay in treatment, infection, inadequate
      immobilization, and improper internal fixation; concomitant infection may be
      present. Pain, mobility of the fracture segments, and radiographic evidence of
      radiolucency did in diagnosis. METHODS AND MATERIALS: Three clinical cases are
      used to present the methods of treatment to manage nonunion following a gunshot
      wound, assault with a blunt object, and a fall. Treatment included antimicrobial
      therapy, fracture site debridement, segment immobilization, and bone grafting.
      Maxillomandibular fixation, debridement, and placement of a reconstruction plate
      were used in the first case; reconstruction plate, autogenous bone graft in a
      polyglactin resorbable mesh, and screw buttons in the second; and custom
      reconstruction plate and iliac crest bone graft in the third. RESULTS AND/OR
      CONCLUSIONS: All cases healed uneventfully. Due to rapid revascularization, use
      of autogenous cancellous bone grafts is preferred to cortical bone. Custom-molded
      polyglactin mesh provides control of the loose cancellous bone graft.

PMID- 11951228
TI  - Special report: lengthening the nose: thoughts on correction with a reexamination
      of some basic principles.
AB  - BACKGROUND AND OBJECTIVES: Providing thin, well-vascularized lining flaps is
      still the most elusive achievement in corrective nasal surgery. The purpose of
      this article is to reexamine some of the principles of correction. METHODS AND
      MATERIALS: To demonstrate the importance of releasing or sectioning nasal lining,
      the authors review the principles of lengthening the nose, illustrated with seven
      clinical cases from their surgical experience and a detailed 12-drawing
      presentation of the surgical approach by Tessier--the senior surgeon. RESULTS
      AND/OR CONCLUSIONS: The nose is the center of the face and a major determinant of
      facial appearance. The short nose has been one of the more difficult conditions
      to treat in rhinoplastic surgery. To optimize the result, procedures developed
      from experience in craniofacial surgery should be combined with the existing
      methods, developed primarily by rhinoplastic surgery and confined to the nasal
      tip.

PMID- 11951229
TI  - Electromyography in craniomaxillofacial trauma.
AB  - BACKGROUND AND PURPOSE: Electromyography is used in conjunction with clinical
      diagnosis to determine the presence and extent of craniofacial injuries; it is
      also an aid in prognosis of recovery. This article reviews the neural
      pathophysiology following trauma and the basic principles of electrodiagnostic
      testing; such understanding helps to determine indications for electrodiagnostic
      testing. METHODS AND MATERIALS: Electrodiagnostic techniques can detect and
      differentiate the degree of injury. There are three major categories of nerve
      injury--neurapraxia, axonotmesis, and neurotmesis. In neuropraxic injuries,
      stimulation distal to the lesion will continue to elicit a response indefinitely;
      in more severe injuries, axonal degeneration begins within 3 to 5 days
      postinjury. RESULTS AND/OR CONCLUSIONS: Electromyography may be used as a
      valuable adjunct to traditional forms of diagnosis and prognosis. The accuracy of
      electrodiagnostic data reported in the literature ranges from 50% to 67% in some
      studies and 77% to 90% in others. Studies with larger patient populations and
      longer follow-up periods are required.

PMID- 11951230
TI  - Peer review in a multispecialty journal.

PMID- 11951231
TI  - Orbital deformity after craniofacial fracture repair: avoidance and treatment.
AB  - BACKGROUND AND OBJECTIVES: To achieve the optimal preoperative appearance
      following craniofacial fracture repair, the surgeon must be facile in the most
      sophisticated reconstructive techniques and able to determine their application.
      The purpose of this article is to describe the common deformities following such
      repairs, outline a strategy to avoid them, and review the surgical techniques to
      correct them. METHODS AND MATERIALS: The deformities are categorized by the
      anatomic zones of the orbit, i.e., zygomatic, frontal, and nasoethmoidal,
      affected by low-, middle-, and high-energy impact. The common types of deformity
      and acute and late treatments are discussed for each category. RESULTS AND/OR
      CONCLUSIONS: The optimal time to correct posttraumatic orbital deformities is
      during the acute phase. Extended open reduction and rigid fixation techniques
      have their own morbidity, which must not outweigh the deformity of an untreated
      or partially treated injury. The results of late reconstruction are always
      limited by scarring of the overlaying soft tissue envelope.

PMID- 11951232
TI  - Understanding nocturnal enuresis and its treatments.
AB  - Nocturnal enuresis is a condition that touches the lives of many children around
      the world. Affected children and their parents may experience feelings of guilt,
      frustration, and anxiety because of their lack of control over the situation.
      Nurses can play an important role in providing education to families in regards
      to the causes and treatment of enuresis. It is important for nurses to understand
      the problem of bedwetting thoroughly so they can assist the family in making an
      informed decision about the various options currently available. Nocturnal
      enuresis (bedwetting) is a common disorder that frequently results in frustration
      and stress on not only the children that experience it, but their parents as
      well. Scharf, Pravda, Jennings, Kauffman, and Ringel (1987) note that an
      estimated five to seven million children in America experience enuresis. Enuresis
      has family and psychosocial aspects, along with financial concerns. Therefore, it
      is important for nurses to be aware of the causes of enuresis, how it affects the
      family, and the current treatments that are available.

PMID- 11951233
TI  - "A home care provider's challenge--caring for the hispanic client in the home".
AB  - It is important for home health care providers to keep in mind that clients from
      different cultures should be assessed and may vary according to 1) communication,
      2) space, 3) time, 4) social organization, 5) environmental control, and 6)
      biological variations. Some variations, which have been evident by some Hispanic
      Americans have been discussed in this article. Careful assessment of the client
      and being aware of issues that differ between and within persons of a cultural
      group can enable the provider to provide culturally appropriate care. This will
      increase the likelihood of successful outcomes to health care interventions and
      optimal health for the client.

PMID- 11951234
TI  - Preceptorship--it works!

PMID- 11951235
TI  - Self-talk for the licensed practical/vocational nurse.
AB  - There are varied opinions on the commonness of self-talk. Some feel self-talk is
      engaged in more by persons who feel insecure and question their performance
      (Cauchon, 1994). Others feel self talk is a process people use continually to
      describe and interpret the world, accurate or inadequate as the case may be.
      (Hansen, Rhode, and Wolf-Wilets, 1991; Braiker, 1989). Regardless of how much
      self-talk the Licensed Practical/Vocational Nurse is aware of in interactions
      with clients, staff, and intraphysically, it is important to assess thoughts for
      their logic or illogic. Illogical thoughts should be replaced by positive words
      of encouragement which will in turn raise the client's, staff members or Licensed
      Practical Nurse's feeling of self concept and level of self-confidence. Making
      self-talk positive is always good professional practice.

PMID- 11951236
TI  - Breakthrough in psychiatric care. Pharmacological treatment of obsessive
      compulsive disorders with implications for nursing care.

PMID- 11951237
TI  - Back to health. An LPN's journey.

PMID- 11951238
TI  - Home care--nursing's Rodney Dangerfield!

PMID- 11951239
TI  - Hospice and palliative nursing: the NBCHPN certification examination.

PMID- 11951240
TI  - Steps for effective medication counseling.

PMID- 11951241
TI  - Confidentiality in home and hospice nursing. Protecting vulnerable populations.
AB  - Nurses are taught early in their educational experience the importance of keeping
      confidential information they have learned about the people for whom they provide
      care. This article describes a scenario where confidentiality is breached and how
      the intended "good works" actually resulted in unintended harm.

PMID- 11951242
TI  - A new look at heart failure.
AB  - Heart failure is the number one hospital admission for the elderly and a leading
      client population for home care with numbers expected to rise steadily during the
      next decade. This article discusses systolic and diastolic heart failure,
      compensatory mechanisms, pathophysiology, and the signs and symptoms of right and
      left-sided heart failure. The most current treatment regimen for managing the
      heart failure patient in the home including medication, diet, activity, and
      patient education is presented.

PMID- 11951243
TI  - Telephone support for persons with chronic mental illness.
AB  - These cases offer evidence of the potential utility of telephone support for one
      of the most challenging segments of the population. This group of clients often
      does not have strong support of any kind. Telephone support shows promise of
      offering cost-effective care for persons with psychiatric disabilities. Home
      healthcare nurses are encouraged to use this information as a basis for exploring
      the use of telephone support as a cost-effective system with their patients.

PMID- 11951244
TI  - Elder suicide: a gate keeper strategy for home care.
AB  - Although home care and hospice patients are admitted with many primary and
      secondary diagnoses, the importance of identifying elders with the potential for
      suicide should still be uppermost in the professional's assessment and ongoing
      evaluation. This article has given many specific suggestions for professionals
      and organizations to consider and implement in addressing this important problem.

PMID- 11951245
TI  - Home healthcare and the Arab-American client.

PMID- 11951246
TI  - The leaders' role in planning for organizational improvement in home care.

PMID- 11951247
TI  - The presidential election and healthcare.

PMID- 11951249
TI  - Needlestick injury: what every nurse should know.

PMID- 11951250
TI  - Additional evidence of the unfortunate changes that are occurring in the nursing
      profession.

PMID- 11951251
TI  - Responding to the cultural and spiritual needs of clients.
AB  - Spirituality has been central to nursing practice since the time of Florence
      Nightingale although for many years spiritual care has fallen into disuse. With
      the increasing movement toward holistic nursing care within a multicultural
      community, the need to integrate cultural sensitivity with spirituality has
      become essential. By incorporating spirituality and cultural dimensions into the
      plan of care, nurses can more holistically provide efficient and quality care
      within both the hospital and community environment.

PMID- 11951252
TI  - Nocturnal enuresis.

PMID- 11951253
TI  - Managing care of the patient with schizophrenia--before and after surgery.

PMID- 11951254
TI  - Developing cultural sensitivity. When your client is Filipino American.
AB  - A nurse caring for a Filipino patient must keep in mind what is known about the
      patient's cultural background so that culturally appropriate care can be
      provided. While many persons with Filipino background appear well assimilated
      into the cultural mainstream of the United States when illness occurs it is very
      likely that behavior will have some basis in the individual's cultural heritage.

PMID- 11951255
TI  - Letting your face do your talking.
AB  - Throughout the world, facial expression is generally noted in conversation and is
      used as an integral part of the communication between individuals. Since nursing
      occurs in an interpersonal arena, nurses need to be especially aware of facial
      expression and eye behavior and the meaning that may be associated with different
      expressions. It is important to understand facial expression from a multicultural
      vantage since the meaning of expressions varies in different cultures.

PMID- 11951256
TI  - Soft tissue deformity after craniofacial fracture repair: analysis and treatment.
AB  - BACKGROUND AND OBJECTIVES: The primary repair of facial fractures requires
      sufficient subperiosteal dissection and mobilization of soft tissues to permit
      accurate fracture reduction. Improper repositioning of soft tissues predisposes
      the site to deformities with subsequent adverse effects on the aesthetics of the
      final result. The purpose of this paper is to describe these deformities, the
      modification of surgical approaches to avoid them, and the various techniques for
      secondary soft tissue reconstruction. METHODS AND MATERIALS: The paper reviews
      the assessment of soft tissue deformity and the principles of soft tissue
      reconstruction in addressing temporal contour deformity, cheek ptosis, eyelid
      deformities, and medial and lateral canthal dystopia. RESULTS AND/OR CONCLUSIONS:
      The morbidity of remote incisions and soft tissue degloving used in primary
      facial fracture repair can be minimized by using a meticulous technique and
      precise soft tissue repositioning at closing.

PMID- 11951257
TI  - Invited review: small versus large plate fixation of mandibular fractures.
AB  - BACKGROUND AND OBJECTIVES: Since the introduction of antibiotics in the late
      1940s, open reduction and internal fixation (ORIF) gradually replaced various
      dental splints and devices as a means of providing additional reduction and
      fixation of mandibular fractures. Stainless steel wire has been recently replaced
      by plate-and-screw fixation. When properly utilized, this method provides
      convalescent function without maxillomandibular fixation (MMF). The purpose of
      this article is to review the evolution of small versus large plate fixation of
      mandibular fractures. METHODS AND MATERIALS: In the context of reports in the
      literature and 26 years of clinical experience, the authors review the types of
      mandibular rigid fixation, healing of fractures, morbidity of fracture repair,
      indications for rigid fixation, and evolution of techniques of treatment. RESULTS
      AND/OR CONCLUSIONS: Although numerous devices and techniques--bone clamps, intra-
      and extramedullary K-wires, metallic mesh, and other means--have been used and
      abandoned, modern plate and screw systems, if not the standard of care, have
      become widely accepted and used.

PMID- 11951258
TI  - Concomitant ocular injuries with orbital fractures.
AB  - BACKGROUND AND OBJECTIVES: The orbital floor may fracture alone, and the fracture
      is then defined as "pure"; when there is a rim involvement, the fracture may be
      defined as "impure". Controversy exists as to the pathophysiology of orbital
      floor fractures and the incidence of orbital rim involvement. The purpose of this
      retrospective review was to determine the incidence of purity in orbital floor
      blowout fractures and the rate of ocular injuries in pure and impure floor
      fractures. METHODS AND MATERIALS: The charts of 250 patients with orbital
      fractures, treated at a primary trauma center between 1992 and 1996, were
      reviewed. All fractures had been examined by the Ophthalmology Service and
      confirmed by high-resolution computerized tomography scans. The average age of
      the patients was 45 years; more than 90% were male. Motor vehicle accidents were
      the most commonly documented mechanism of injury, followed by interpersonal
      violence and falls. Almost 50% could not be categorized for mechanism of injury.
      RESULTS AND/OR CONCLUSIONS: The incidence of ocular injuries in pure fractures (n
      = 54; 5.6%) was higher than in impure fractures (n = 26; 2.0%) (p = 0.05).
      Serious visual injuries following orbital fractures occurred in 17.1% of the
      patients; they were more common in patients with pure fractures.

PMID- 11951259
TI  - A plate is not just a plate, and a screw is not just a screw.

PMID- 11951260
TI  - Orbital floor repair with titanium mesh screen.
AB  - BACKGROUND AND OBJECTIVES: Surgical repair of the acutely fractured orbit strives
      to restore appearance, preserve ocular and orbital function, and avoid
      enophthalmos or hypoglobus. Repair is achieved with autologous bone graft,
      synthetic substitutes, or both. The purpose of this article is to present an
      alternative procedure--use of implants, cut from a titanium mesh screen, without
      bone graft. METHOD AND MATERIALS: A total of 51 orbital floor fractures in 43
      patients were repaired with titanium mesh screen implants. In three patients with
      bilateral orbital floor fractures repaired with titanium mesh, intraoperative
      symmetry was improved with bone graft added to the mesh on one side. RESULTS
      AND/OR CONCLUSIONS: Follow-up was available for 42 orbits in 35 patients and
      averaged 9 months. The transconjunctival approach with lateral canthotomy yielded
      better results than the subciliary approach, which often caused transient scleral
      show or ectropion. One patient underwent surgery for ectropion following a
      subciliary approach, and one patient developed a 4-mm enophthalmos. Routine bone
      grafting is unnecessary, even in large floor defects. Titanium mesh implants are
      a simple and reliable option for orbital floor repair.

PMID- 11951262
TI  - Surgical approaches to mandibular condylar fractures: a review.
AB  - BACKGROUND AND OBJECTIVES: The estimates of mandibular condyle fracture incidence
      lack consensus, as these fractures are frequently overlooked or misdiagnosed,
      resulting in adverse effects. The purpose of this article is to review the
      anatomy of the mandibular condyle and the surgical approaches currently
      available. METHODS AND MATERIALS: Surgical treatment of mandibular condyle
      fractures remains controversial, due to the indications and difficulty with the
      associated vital structures. To aid in selecting the appropriate approach, the
      authors present a review of the mandibular anatomy and the approaches utilized,
      as reported in the literature and observed in the clinical practice of the
      authors. RESULTS AND/OR CONCLUSIONS: In selecting the approach, the knowledge of
      the mandibular anatomy is vitally important. A survey found that the
      preauricular, submandibular, and intraoral approaches (in that order) were
      preferred. When treating the fractured mandibular condyle with open reduction and
      internal fixation, a thorough knowledge of the anatomy of vital structures,
      exercise of care, and careful dissection through the soft tissues will reduce the
      risk for morbidity.

PMID- 11951261
TI  - Facial trauma and ocular/orbital injury.
AB  - BACKGROUND AND OBJECTIVES: Ocular injuries occur commonly in patients with facial
      trauma. Patients with significant eye injuries may present with grossly normal
      eyes and good visual acuity; however, subsequent ocular disorders may become
      apparent. The estimates of incidence vary considerably. Trauma is the second
      leading cause of blindness, and a review is, therefore, warranted. METHODS AND
      MATERIALS: Several extensive studies are reviewed. Blunt and penetrating trauma
      are examined by their respective subdivisions. The initial assessment and
      ophthalmologic examination of patients with facial trauma are discussed, and the
      type of injury that may occur secondary to trauma is delineated. Management is
      reviewed and discussed, including a recently developed diagnostic scoring system.
      Three clinical cases illustrate the procedure. RESULTS AND/OR CONCLUSIONS: The
      diagnosis of ocular injuries resulting from trauma is difficult. The recently
      introduced scoring system was found to improve the procedure. Based on this
      system, the authors have devised an algorithm to assist the clinician, with
      emphasis on visual acuity and the importance of visual examination.

PMID- 11951263
TI  - Facial fracture classification: current thoughts and applications.

PMID- 11951264
TI  - Delayed rupture of traumatic intracranial pseudoaneurysm in a child following
      gunshot wound to the head.
AB  - BACKGROUND AND OBJECTIVES: Traumatic intracranial aneurysms (TICAs) are highly
      unstable lesions that may rupture within minutes after formation or remain
      quiescent for several weeks and manifest with delayed hemorrhage and neurologic
      deterioration. Mortality following a rupture may be 30% to 40%. Among all
      cerebral aneurysms, the incidence of TICAs is less than 1%; 20% to 30% of TICAs
      occur in children. METHODS AND MATERIALS: A child with a low-caliber
      craniocerebral gunshot wound deteriorated neurologically 12 days after the
      initial injury and emergency evacuation of an intracranial hematoma. A new
      massive left frontal hematoma was discovered, caused by the rupture of an
      unsuspected left pericallosal artery pseudoaneurysm. The new hematoma was
      evacuated, and the aneurysm was trapped using microsurgical techniques. RESULTS
      AND/OR CONCLUSIONS: A high index of suspicion should be maintained for delayed
      pseudoaneurysm genesis and rupture. A cerebral arteriogram should be obtained
      when significant subarachnoid hemorrhage or intraparenchymal hematomas are
      present, when missiles traverse major arteries, or when the pterional or
      cranioorbitofacial regions are violated. Treatment should be prompt.

PMID- 11951265
TI  - Progress toward an international journal of cranio-maxillofacial trauma.

PMID- 11951266
TI  - Application of endoscope-assisted minimal-access techniques in orbitozygomatic
      complex, orbital floor, and frontal sinus fractures.
AB  - BACKGROUND AND OBJECTIVES: Minimal-access endoscope-assisted techniques have been
      adapted for facial rejuvenation surgery over the past 5 years, allowing smaller
      incisions, limited dissection, and shorter recovery times. Their increasing
      popularity prompted the author to investigate their application in facial trauma
      patients. METHODS AND MATERIALS: Endoscope-assisted minimal-access surgical
      approaches were developed in cadavers and applied in the management of frontal
      sinus, orbital floor, and orbitozygomatic complex fractures over a 3-year period.
      At a Level 1 regional trauma center, these techniques were applied in 33 of 161
      patients with facial fractures. Surgical techniques, applications of endoscope
      technology, and indications/contraindications are presented. A technique, known
      as the pulse test, was developed for assessing the integrity of the orbital
      floor. RESULTS AND/OR CONCLUSIONS: Endoscope-assisted minimal-access surgical
      techniques have a definite but perhaps limited application in the diagnosis, as
      well as in some aspects of the surgical treatment of fractures of the anterior
      table frontal sinus, orbitozygoma, and orbital floor. New indications for these
      techniques will depend upon the development of improved instrumentation.

PMID- 11951267
TI  - Lag screw fixation of mandibular fractures.
AB  - The lag screw is the simplest means of rigid internal fixation. By virtue of its
      ability to compress bone fragments without the use of a bone plate, it has wide
      application and achieves great stability. This article presents techniques to
      apply lag screws to fractures of the mandibular symphysis, the mandibular body,
      and the mandibular angle. Results are reviewed in studies of 315 patients whom
      the author has treated with lag screw fixation. The advantages of the lag screw
      technique over bone-plate fixation, such as a more rapid application, obviation
      of the need to adapt a bone plate, minimal displacement of bone segments, and the
      rapid application of fixation without diminishing the rigidity of the fracture
      reduction, are discussed, as are the technique's contraindications.

PMID- 11951268
TI  - The use of the C-Arm in reduction of isolated zygomatic arch fractures: a
      technical overview.
AB  - Isolated zygomatic arch fractures account for approximately 10% of all zygoma
      fractures. Numerous techniques have been described to reduce these fractures
      using a variety of approaches. Successful reductions are often difficult to
      evaluate clinically because of the great amount of swelling that often
      accompanies these fractures. Postoperative radiographs are often the only way to
      assess the adequacy of the reduction. This article describes a technique that
      uses the C-Arm to quickly and accurately evaluate the reduction intraoperatively
      so that appropriate corrections can be made. A case report of a patient who
      suffered multiple orthopedic injuries and a w-shaped depressed fracture of the
      left zygomatic arch is presented. The C-Arm can obviate the need for
      intraoperative radiographs that, due to technician and film processing delays,
      add significantly to operative time.

PMID- 11951269
TI  - Traumatic auricular hematoma: a case report.
AB  - Traumatic recurrent auricular hematoma can be a challenging medical problem, with
      complications resulting in cauliflower ear. Proper management often depends on an
      understanding of the pathophysiology and pathogenesis of fibroneocartilage--an
      abnormal fibrous cartilage formation in response to injury. Traditional treatment
      by incision and drainage, and compression dressing technique may be inadequate in
      the setting of recurrent or chronic hematoma. Instead, excision of the
      fibroneocartilage is essential in promoting hematoma resolution and wound
      healing. Appropriate treatment of auricular hematoma can reduce needless cosmetic
      deformity and can avoid difficult secondary reconstruction. The authors present a
      case of recurrent auricular hematoma and review its pathophysiology and current
      therapy.

PMID- 11951270
TI  - An algorithm for management of residual posttraumatic calvarial defects in
      adults.
AB  - For the discussion of options in late reconstruction of residual posttraumatic
      calvarial defects in adults, the calvaria is divided into three reconstructive
      zones. Zone 1 comprises the frontal sinus region and the contour of the
      supraorbital brow; Zone 2 comprises the smooth, cosmetically visible prehairline
      forehead; Zone 3 comprises the posthairline area and the calvaria. The particular
      reconstructive requirements (autogenous bone versus alloplastic material) of each
      zone are described and illustrated with clinical cases. The merits of bone from
      various donor sites and those of alloplastic material are discussed. The authors
      present an algorithm of reconstructive choices for residual posttraumatic
      calvarial defects in adults based on the nature of the defect and the aesthetic
      reconstructive zone.

PMID- 11951271
TI  - The need for rigid fixation of combined parasymphyseal and bilateral subcondylar
      fractures.
AB  - Both miniplate and larger fracture plate fixation techniques have been utilized
      successfully in the treatment of mandibular fractures. Parasymphyseal fractures
      which occur in conjunction with bilateral subcondylar fractures, however,
      represent a special fracture pattern that is not well managed with miniplate
      fixation. Miniplates do not have the tensile strength to resist the strong,
      muscular-deforming forces that act on these fractures. This fracture pattern is
      best managed with anatomic symphyseal reduction and internal fixation with a 2.7
      mm mandibular fracture plate and a 2.0 mm tension band plate. The subcondylar
      fractures can then be managed with either intermaxillary fixation or open
      reduction. This approach provides good functional results and can prevent late
      complications.

PMID- 11951272
TI  - The frontonasal flap for increased exposure in posttraumatic nasal deformity: a
      technical overview.
AB  - Nasal reconstruction continues to be a surgical challenge. The prominent location
      of the nose, the unique quality and texture of its skin, and the intricacies of
      its cartilaginous and bony infrastructure demand careful attention to fine
      detail. Attempts to refine reconstructive techniques have resulted in a myriad of
      local flaps. The frontonasal flap is well-described and reliable, but it is
      infrequently used. A brief review of the literature is presented. The authors
      describe a unique case of a 64-year-old woman with posttraumatic nasal tip and
      dorsal deformity. The frontonasal flap provided soft tissue coverage for the
      nasal tip and allowed excellent exposure for reconstruction of the hard nasal
      framework with cartilage and bone grafts. It provides local tissue with excellent
      contour, color, and texture match, and can be performed in one stage.

PMID- 11951274
TI  - Posttraumatic anosmia in craniofacial trauma.
AB  - Although the clinical implications of anosmia can be significant, posttraumatic
      anosmia is generally given relatively little attention in the clinical setting.
      Patients who sustain craniofacial trauma are most at risk. The incidence of
      posttraumatic anosmia varies according to the severity of injury and has an
      overall estimated incidence of 7%. Factors that increase the risk of developing
      anosmia include anterior skull base fractures, bilateral subfrontal lobe injury,
      dural lacerations, and cerebrospinal fluid leakage. Recovery of function has been
      estimated to be approximately 10%. Time of recovery, if it occurs, varies between
      8 weeks and 2 years. Presented herein are the clinical, radiographic,
      pathophysiologic, and anatomic substrata of posttraumatic anosmia.

PMID- 11951275
TI  - Traumatic intracranial aneurysms complicating anterior skull base surgery.
AB  - Traumatic cerebral aneurysm formation following closed head injury is uncommon,
      although well documented in the literature. Aneurysmal development following
      surgical procedures on the anterior skull base is extremely rare. This article
      reports successful neurosurgical management of 3 cases of anterior circulation
      aneurysms that developed following relatively straightforward rhinological
      procedures. These cases illustrate the vulnerability of the vessels of the
      anterior circle of Willis; they also document the sites of penetration of the
      anterior skull base. As reported in the literature, most such aneurysms occur
      following transsphenoidal surgery. The clinical procedures, radiological follow
      up, and the surgical management are outlined; three cases are utilized to
      illustrate this complication. The causes of such iatrogenic injury are discussed,
      with emphasis on strategies for the avoidance of such injuries.

PMID- 11951276
TI  - Hemorrhagic cyst following remote alloplastic implantation for orbital floor
      fracture repair.
AB  - Hemorrhagic cyst formation may occur within months or years following repair of
      orbital fractures with alloplastic materials. Patients present with a sensation
      of pressure in the involved orbit, double vision, and globe displacement.
      Evaluation must rule out infectious, inflammatory, and vascular etiologies.
      Computerized tomography scans reveal a soft tissue density surrounding the
      alloplastic implant. Drainage of the cyst and fibrous capsule, with excision of
      the capsule and removal of the alloplastic implant, is curative. This article
      presents three clinical cases, highlighting the evaluation and management of this
      postsurgical development. Use of the protocol described resulted in complete
      resolution of all clinical symptoms, and the CT scans were normal. As these
      materials will continue to be utilized, surgeons should be aware of this
      potential delayed complication and its management.

PMID- 11951277
TI  - Brown's syndrome diagnosed following repair of an orbital roof fracture: a case
      report.
AB  - The upgaze deficit of Brown's syndrome differs from the upgaze deficit of an
      orbital floor fracture with entrapment. In Brown's syndrome, the upgaze
      limitation is most evident in adduction of the eye. This difference may be
      difficult to establish at times, particularly beneath the periorbital edema of an
      acute traumatic injury. Nevertheless, it is important to recognize this
      differentiation, since the approach to management of these two clinical entities
      is distinctly dissimilar. Brown's syndrome is produced by restriction of the
      superior oblique muscle tendon, usually in the region of the trochlea. In the
      course of describing a case of Brown's syndrome, recognized following the repair
      of an orbital roof fracture, issues related to etiology, diagnosis, and
      management are discussed. In the case presented, surgical repair of the left eye
      was performed.

PMID- 11951278
TI  - Management of avulsive injuries of the nasal bones: review of the literature and
      three case reports.
AB  - Blunt contusions, lacerations, and avulsion-type trauma are the most often
      reported nasal injuries sustained in motor vehicle accidents. The nasal skeleton
      and soft tissues are frequently involved and may require surgical repair of the
      injuries. The primary reconstruction often requires the use of autogenous grafts,
      and secondary revision surgery may be necessary. The treatment may require a
      multidisciplinary surgical team or a single surgeon who knows how to manage the
      injury. Optimally, the reconstruction of nasal bone avulsions is performed
      primarily, using autogenous graft materials. This article presents reconstruction
      of the nasal deformities in 3 patients involved in motor vehicle accidents. The
      authors describe and evaluate the various graft materials and surgical techniques
      utilized. The advantages and disadvantages of autogenous and alloplastic
      materials are discussed. Studies with more patients and long-term follow-up are
      required for a definitive evaluation.

PMID- 11951279
TI  - Pediatric zygomatico-orbital complex fractures: the use of resorbable plating
      systems. A case report.
AB  - Maxillofacial trauma in the pediatric population is infrequent--only 5% of all
      facial fractures occur in children. Operative intervention is indicated when a
      displacement of normal structures is present, resulting in either a functional or
      cosmetic deformity. Some midface fractures in children may be managed with closed
      reduction and maxillomandibular fixation. When open reduction is indicated, plate
      and-screw fixation has been the preferred method of stabilization. This article
      presents a case of an isolated zygomatico-orbital complex fracture in a 6-year
      old boy. Open reduction and internal fixation of the fractures through a
      preexisting facial wound were performed using a resorbable plate-and-screw
      system. A review of the literature and a discussion of the technique precede the
      case presentation. The rapid healing of pediatric facial bones does not obviate
      the need for fracture reduction and fixation with titanium plates and screws. The
      resorbable system offers an alternative with excellent results.

PMID- 11951280
TI  - Managing the emergency airway in Le Fort fractures.
AB  - Le Fort fractures are a part of the facial fracture spectrum, sustained from
      significant forces of impact to the midface. The mechanism of airway obstruction
      in Le Fort fractures is attributed to midface instability with posterior inferior
      displacement into the oropharyngeal airway. Otolaryngologists often participate
      in the evaluation and management of such patients, securing the airway, if
      necessary. It is important, therefore, to understand the mechanisms responsible
      for acute airway obstruction in these types of fractures. A retrospective review
      of 64 cases of Le Fort fractures, representing a 3-year period, was performed to
      determine the factors responsible for acute airway obstruction. The review
      disclosed that airway obstruction is due most often to hemorrhage into the upper
      airway from multiple sources, with inability to handle blood and the oral
      secretions. An emergency airway was required by one third of the patients with Le
      Fort fractures in this review.

PMID- 11951281
TI  - Traumatic chronic TMJ dislocation: report of an unusual case and discussion of
      management.
AB  - Dislocation of the temporomandibular joint (TMJ) is most often spontaneous, but
      it can be associated with direct or indirect head and neck trauma. The disorder
      may be treated in general by simple closed techniques, if managed acutely. If the
      dislocation becomes chronic, however, open reduction is usually required. The
      article discusses various methods for an open surgical approach described in the
      literature. A case of a prolonged TMJ dislocation is presented, involving a
      severe bilateral mandibular dislocation with the condyles displaced into the
      infratemporal fossa and the lateral poles of the condyles articulating on the
      inner aspect of the zygomatic arch. An open approach, involving masseter,
      temporalis, and the medial pterygoid muscles, was utilized, followed by the use
      of scissors mouth props, Erich arch bars, and postoperative elastic traction.

PMID- 11951282
TI  - Congress shows changing face of palliative care.

PMID- 11951283
TI  - Young adults with cancer: the effect of the illness on parents and families.
AB  - This article is based on the findings from a qualitative study involving a
      collection of narratives written by the parents of young adults with cancer. It
      examines the effects of the illness on parents and family and illustrates that
      young people aged 18-25 years face particular difficulties when diagnosed with a
      life-threatening illness. The article focuses on how these difficulties are
      experienced by the parents of young adults who are attempting to maintain
      'normality' and perhaps also manage newly established sexual relationships. The
      article considers the problems for parents, e.g. the ownership of medical
      information when the young adult is of age but dependent on his/her parents, the
      effect on siblings and the financial implications of the illness for the family.
      A gap in the knowledge of professionals and families relating to these effects
      may result in families believing that the acute problems they face are caused by
      their particular family dynamics rather than the life-stage of their young adult
      children.

PMID- 11951284
TI  - The experience of transition to palliative care services: perspectives of
      patients and nurses.
AB  - The care of patients whose illnesses cannot be cured places many stresses on
      health professionals (both generalist and specialist), and more importantly on
      patients and families. The complexities for all concerned in the process of
      referral to palliative care services should not be underestimated, however there
      is evidence that the referral process could be better handled by all health
      professionals. With greater understanding of the dynamics of care, the crisis of
      living with an incurable illness and dying can be lessened for patients. This
      article reports on a qualitative research project undertaken at a large
      metropolitan palliative care service and its referring public hospital. Patients
      and nurses were interviewed to identify issues relating to the care of patients
      and families newly referred to palliative care. The findings of this research
      identify themes in relation to the transition of patients from acute curative to
      palliative care services, e.g. pace and timing of the transition, fear and
      (mis)understanding, accepting palliative care, information and education on
      palliative care, and peer support and supervision for palliative care nurses.

PMID- 11951285
TI  - Silent voices, hidden practices: exploring undiscovered aspects of cancer
      nursing.
AB  - This is an abridged version of the sixth annual Robert Tiffany Lecture presented
      on 14 March 2001 at the Royal Marsden's National Cancer Nursing Conference in
      London. Robert Tiffany was the chief nurse at the Royal Marsden, London from 1976
      until 1993. The lecture is named after him to commemorate his work establishing
      oncology nursing across the world and, more specifically, developing its practice
      at the Royal Marsden. This lecture examined the silences that exist in nursing
      practice--the things that nurses do not talk about or even understand as part of
      their work. Drawing on research that explored nurse-patient relationships in
      cancer and palliative care settings, this lecture highlighted the closeness and
      intimate nature of such relationships and reflected on their impact on nurses,
      patients and nursing practice.

PMID- 11951286
TI  - Views of nurses, patients and patients' families regarding palliative nursing
      care.
AB  - This article presents the findings of a 3-phase project, that used the
      qualitative approach of storytelling to examine the degree of congruency between
      the perceptions of nurses, patients and patients' families respectively, in
      relation to the nature and effects of palliative nursing care. The major
      difference in the stories was the slight emphasis on the personal qualities
      palliative nurses bring to their work and the activities in which they engage.
      Nurses emphasized their work activities, whereas patients and relatives gave
      equal emphasis to the positive and negative aspects of nurses' qualities and
      activities.

PMID- 11951287
TI  - Preparation, information and liaison: conducting successful research in
      palliative care.
AB  - Palliative care professionals are increasingly exposed to, and under pressure to
      participate in, research to promote evidence-based practice. This may pose
      challenges and tensions within normal working practices. This article draws on
      the results of a small qualitative study that explored the experiences of a group
      of specialist nurses at an independent hospice involved in palliative care
      research. By reflecting on their experiences and the difficulties they
      encountered, primarily with regard to obtaining informed consent from patients to
      take part in the research, this article explores issues relevant to practitioners
      and researchers when conducting palliative care research involving patients. It
      concludes by suggesting guidelines for conducting good quality research.

PMID- 11951288
TI  - Specialist palliative care in the UK: its future and the effects of NHS reforms.
AB  - This article examines the impact legislative developments in the UK have had, and
      are likely to have, on health care in general and how specialist palliative care
      providers may need to adapt to these changes. The focus of adaptation is on
      communication and multidisciplinary teamwork. A brief review of the previous
      Conservative government's reforms offers a background to understanding how the
      current Labour government agendas affecting health and social care have been
      developed. Ideas are put forward to ensure that specialist palliative care
      provision is maintained and developed within the current structure of the health
      service.

PMID- 11951289
TI  - Women at high risk for cardiovascular disease.

PMID- 11951291
TI  - Home care is nursing, too!

PMID- 11951290
TI  - Little people need help, too!

PMID- 11951292
TI  - A question about the appropriate nursing approach.

PMID- 11951293
TI  - Improving organizational performance standards: data collection in home care.

PMID- 11951294
TI  - How to determine if PPS will provide adequate resources for your population: one
      agency's experience.
AB  - Extensive research was conducted to develop the proposed Prospective Payment
      System (PPS) and to ensure that it will adequately cover the costs of care for
      Medicare beneficiaries receiving the home health benefit. However, there is
      tremendous variation among the patients served by agencies, meaning that the
      system will impact each agency somewhat differently. Using the methods outlined
      in this article, agencies can determine potential problem areas under PPS,
      enabling them to develop and implement solutions before October 1, 2000.

PMID- 11951295
TI  - MedPAC reports to Congress.

PMID- 11951296
TI  - OSHA revises bloodborn pathogens compliance directive.

PMID- 11951297
TI  - Homebound status.

PMID- 11951298
TI  - Teaching the older patient in the home assessment and adaptation.
AB  - The proportion of older patients in the home care and hospice nurses' caseload is
      increasing. This article focuses on specific assessment and OASIS items to
      consider when implementing teaching interventions for older patients. Teaching
      strategies and adaptations are suggested for each assessment area.

PMID- 11951299
TI  - The meaning of home: how it shapes the practice of home and hospice care.
AB  - Nurses often hear clients and their families express a strong desire to "go home"
      from the hospital or nursing home. The purpose of this article is to explore what
      they mean when they make this request and how this meaning of home can shape the
      practice of home and hospice care. To do this, definitions of home and a health
      at-home model are described and applied through a case study.

PMID- 11951300
TI  - Alternatives to restraints: what patients and caregivers should know.
AB  - Current nursing practice mandates that patients be provided safe care in the
      least restrictive environment possible. This article discusses specific unsafe
      patient behaviors, their possible causes, and alternatives to the use of
      restraints in the home. The role of the home care and hospice professional is
      presented.

PMID- 11951301
TI  - Home care nursing for persons with congestive heart failure: description and
      relationship to hospital readmission.
AB  - Although home care nursing has been associated with a lower rate of repeated
      hospitalization of persons with congestive heart failure, little is known about
      this relation. This study examined variables that reflect information about
      demographic characteristics, clinical status, nursing services, and repeated
      hospitalization for persons admitted with a primary diagnosis of congestive heart
      failure to one home care agency during one fiscal year. Implications related to
      assessment, documentation, patient instruction, and further research are
      discussed.

PMID- 11951302
TI  - Performance improvement: the final phase of an organization's performance.

PMID- 11951303
TI  - Learning home telehealth: new opportunities.
AB  - This article outlines a telehealth training program through East Carolina
      University. As clinicians and managers learn more about this new way to deliver
      services, this course provides a needed primer of this emerging field.

PMID- 11951304
TI  - What nurses and managers expect from point of care technology.

PMID- 11951305
TI  - Using guided imagery to reduce pain and anxiety.
AB  - Guided imagery is a therapeutic technique that allows a person to use his or her
      own imagination to connect their body and mind to achieve desirable outcomes such
      as decreased pain perception and reduced anxiety. This article describes the use
      and application of guided imagery for clients in the home and the benefits to the
      agency. A step-by-step approach to teaching clients how to use guided imagery is
      included.

PMID- 11951306
TI  - The kitchen table discussion: a creative way to discuss end-of-life issues.
AB  - Home care and hospice nurses are uniquely positioned to facilitate early
      discussions about patient's care wishes and goals at the end of life. This
      article presents a definition of advance care planning, why it is important, a
      model for facilitating the discussion, suggestions for overcoming barriers, and
      tools to assist nurses in feeling more comfortable integrating the subject into
      daily practice.

PMID- 11951307
TI  - Using M&E and telephonic case management in PPS.
AB  - With appropriate reimbursement, the prospective payment system (PPS) can provide
      the opportunity to provide care under Medicare the way it was meant to be:
      individualized, quality care, planned and coordinated to achieve optimum cost
      effective outcomes based on individual patient need. This article explores how
      management and evaluation of a care plan and telephonic case management can be
      used in PPS.

PMID- 11951308
TI  - How will surveyors evaluate OASIS compliance?

PMID- 11951309
TI  - Maternity nurse's attitudes towards Mexican-American clients.
AB  - This pilot study in one maternity unit in a hospital in the mid-west indicated
      that nurses were interested in information about the culture and beliefs of their
      Mexican-American clients and that there was a need for assistance in
      communicating with clients who could not speak English. The pilot study, while
      elementary in design, provided information on which to make change in the care
      provided. This study illustrates the importance of use of simple research
      strategies to make appropriate nursing care decisions.

PMID- 11951310
TI  - What do Bo Jackson, Clara Barton, Moses, Bruce Willis and Sir Isaac Newton have
      in common?

PMID- 11951311
TI  - "Nursing is your passport to challenge and success".
AB  - Nursing can be a career that will bring you great joy and rewards. Undoubtedly,
      your journey to attaining your LP/VN license will be filled with many good times
      as well as difficult times. Organization and discipline will help to make this
      time a more positive experience. Once you've become licensed, your possibilities
      are endless. Nursing can be your passport to success.

PMID- 11951312
TI  - Mr. Quarantine, meet miss Liberty.

PMID- 11951313
TI  - Tracking the anthrax attacks.

PMID- 11951314
TI  - Why we blow ourselves up.

PMID- 11951315
TI  - How the trauma takes its toll on us.

PMID- 11951316
TI  - How much is a living wage?

PMID- 11951317
TI  - The doctor is armed.

PMID- 11951318
TI  - The curious case of Kava.

PMID- 11951319
TI  - And in his 82nd year, John Paul II rested.

PMID- 11951320
TI  - When aspirin doesn't work.

PMID- 11951321
TI  - ACLS 2000: overview of changes to the guidelines.
AB  - Emergency treatment measures in the setting of a cardiopulmonary arrest have
      recently been reclassified according to the strength of evidence in support of
      their use. As a result, there are new recommendations that must be incorporated,
      both in the management of patients in cardiac arrest and those with clinical
      findings that have the potential to deteriorate and become life-threatening. This
      article provides an overview of the 2000 ACLS guidelines, with particular
      emphasis on new developments in the management of patients with acute coronary
      syndromes, changes in the tachycardia algorithms, and recommendations pertaining
      to endotracheal intubation.

PMID- 11951322
TI  - Understanding sepsis: from SIRS to septic shock.
AB  - Sepsis remains the leading cause of death in non-coronary ICU patients, despite
      improvements in supportive treatment modalities such as antimicrobial drugs and
      ventilation therapy. Further, the incidence of sepsis is projected to increase in
      years to come, related to factors including a rise in immunosuppressed patient
      populations and more widespread use of invasive lines and procedures. In this
      article, the authors seek to advance nurses' understanding of sepsis by reviewing
      the SIRS to septic shock paradigm and using a case study to illustrate how a
      patient progressed along the continuum. The role of the critical care nurse is an
      important aspect of the care of these patients. Early identification of patients
      at risk for, or who are developing, sepsis is crucial in order to improve patient
      outcomes.

PMID- 11951323
TI  - Re: Oxygenation in prone position.

PMID- 11951324
TI  - Cardiovascular effects of epinephrine in hypertensive dental patients.

PMID- 11951326
TI  - Peeling plaque. Researchers remain optimistic about a vaccine against
      Alzheimer's.

PMID- 11951327
TI  - Ecology. Lion versus lamb.

PMID- 11951328
TI  - Face shift. How sleeping sickness parasites evade human defenses.

PMID- 11951329
TI  - Drams of drugs and dregs. Excreted chemicals pollute U.S. streams.

PMID- 11951330
TI  - IP rights--and wrongs.

PMID- 11951332
TI  - Journey to the farthest planet.

PMID- 11951333
TI  - Wireless data blaster.

PMID- 11951331
TI  - Atherosclerosis: the new view.

PMID- 11951334
TI  - The mammals that conquered the seas.

PMID- 11951335
TI  - Extreme light.

PMID- 11951336
TI  - Rethinking green consumerism.

PMID- 11951337
TI  - Terrorize people, save animals. Animal-rights activists are close to destroying a
      major drug-testing firm.

PMID- 11951338
TI  - Preventable injuries are booming in kids' sports. Dangerous games.

PMID- 11951339
TI  - Smallpox redux. We suddenly find ourselves with plenty of vaccine. Should we go
      ahead and inoculate everyone now?

PMID- 11951340
TI  - Wreckless teens. Kids are impatient to get behind the wheel. But putting on the
      brakes is clearly saving lives.

PMID- 11951341
TI  - A deepening disorder.

PMID- 11951342
TI  - Progress towards tuberculosis control, India, 2001.

PMID- 11951344
TI  - Too many voices. Group sees a need; others wonder what.

PMID- 11951343
TI  - Impact of large-scale rectal artesunate deployment in the emergency management of
      malaria.

PMID- 11951345
TI  - An Ardent overture. System seeks to gain N.M. not-for-profit.

PMID- 11951347
TI  - If you have to ask, you can't afford it. Boutique practices getting a hard look
      from government, doctors' group.

PMID- 11951346
TI  - Getting a foot in the door. Care access returns to agenda with reports' findings.

PMID- 11951348
TI  - Ruts in the rural field. Providers step up efforts to save physician waivers.

PMID- 11951349
TI  - Pros and CONs. Tennessee execs looking for down-home recipe to fix certificate-of
      need law.

PMID- 11951350
TI  - Out in the cold. A letter leaves hospitals to sacrifice for a physician update as
      the AMA backs off.

PMID- 11951351
TI  - Can L.A. mend the safety net? Without a radical overhaul, the county health
      system will fail.

PMID- 11951352
TI  - Steely competition. In the Pittsburgh market, it's behemoth healthcare system vs.
      dominant insurer. And the battles have become fiery indeed.

PMID- 11951353
TI  - Fraud detectors. Payers and health insurers are turning to powerful new software
      to help identify questionable healthcare claims in real time.

PMID- 11951354
TI  - Straight talk: new approaches in healthcare. Physician practice turnaround in an
      integrated delivery system.
AB  - This is the second installment in a series of group discussions by top executives
      on key issues in healthcare today. Straight Talk is present by Modern Healthcare
      and PricewaterhouseCoopers. This session tackles the subject of physician
      practice turnaround in an Integrated Delivery System. The discussion was held on
      March 5, 2002 at Modern Healthcare's Chicago headquarters, moderated by Charles
      S. Lauer.

PMID- 11951355
TI  - Loyal clients. Despite Arthur Andersen's indictment, healthcare companies aren't
      defecting.
AB  - In contrast to about 50 defections by public companies, many healthcare clients
      of Andersen are standing by the troubled auditor--at least for now. Saying that
      it's too soon to judge, clients such as the Catholic Health Association are
      sitting tight to see what the fallout is from the Enron scandal before making any
      decisions. And even if many part ways with Andersen, there's a host of
      consultants to take its place.

PMID- 11951356
TI  - Who is the public health nurse?

PMID- 11951357
TI  - Florence Nightingale, where are you?

PMID- 11951358
TI  - Congestive heart failure.

PMID- 11951360
TI  - It's my bag! Public health nursing across Nebraska.

PMID- 11951359
TI  - Guilty as charged.

PMID- 11951362
TI  - History's healer: the midwife.

PMID- 11951363
TI  - Hospital associations test drive JCAHO core measures effort.

PMID- 11951364
TI  - A primer on JCAHO performance data.

PMID- 11951365
TI  - New quality indicator tools available from AHRQ.

PMID- 11951366
TI  - Detroit Medical Center scores with outsourcing IT strategy.

PMID- 11951367
TI  - Smaller amb surgery facilities perform better, surveys find.

PMID- 11951368
TI  - Price survey. Pacemaker deals abound in 2002.

PMID- 11951369
TI  - Spinal cage contracting: it's a backbreaking chore.

PMID- 11951370
TI  - Hospitals asked to review disaster packs.
AB  - As the nation somberly marked the six-month anniversary of the terrorist attacks
      on New York and Washington, a group of materials managers and vendors finished
      drafting a supply list to be used by hospitals in conjunction with a disaster
      readiness plan.

PMID- 11951371
TI  - At DoD, there's always a war on waste.
AB  - The war on terror may have caused a rethinking of transport logistics and the
      adequacy of emergency stockpiles, but it is the war on waste that has been
      gradually transforming military procurement for the past several years.

PMID- 11951372
TI  - From O2 to H2S: a landscape view of gas biology.
AB  - The majority of molecular oxygen (O2) consumed in the body is used as a substrate
      of cytochrome c oxidase to maintain oxidative phosphorylation for ATP synthesis.
      Rest of the O2 is used for oxidative biosynthesis including synthesis of
      vasoactive substances such as prostaglandins and secondary gaseous mediators such
      as nitric oxide (NO) and carbon monoxide (CO). Thus, O2 is not only used for
      maintenance of energy supply but also for regulating blood supply into tissues.
      Nitrous oxide (N2O), laughing gas for anesthesia, is generated endogenously
      through NO reductase in bacteria and fungi, and has recently been shown to
      modulate N-methyl-D-aspartic acid (NMDA) receptor function. A number of other
      biologically active gases could participate in regulation of cell and tissue
      functions. Carbon dioxide (CO2) is generated mainly through the Krebs cycle as a
      result of glucose oxidation and serves as a potent vasodilator, and hydrogen
      sulfide (H2S) synthesized through degradation of cysteine has recently been
      postulated to be a neuromodulator, although their receptor proteins for signaling
      have not been verified as a discernible molecular entity. Easy penetration allow
      these gases to access the inner space of receptor proteins and to execute their
      biological actions. These gases are generated and consumed in anaerobic bacteria
      through varied reactions distinct from those in mammals. This review summarizes
      recent information on mechanisms for gas generation and reception in biological
      systems.

PMID- 11951373
TI  - Characteristics of elderly patients presenting to the emergency department with
      injury.
AB  - BACKGROUND: In Japan, emergency departments (ED) receive a large proportion of
      elderly patients each year. As such, injuries in the elderly are a common reason
      for presentation to the ED. Knowledge about the characteristics of injuries
      presenting to the ED would be invaluable in devising strategies to prevent injury
      in the elderly. OBJECTIVE: To analyze the characteristics of injuries in the
      elderly presenting to the ED and compare them with those of the younger
      population. SETTING: The ED at Keio University Hospital, a large inner city
      teaching hospital located in Tokyo. METHOD: A retrospective analysis of data
      extracted from the ED database of the Keio University Hospital. Information
      regarding patients aged 65 years or above presenting with injury was analyzed and
      compared with those aged less than 65 years. Prehospital triage by emergency
      personnel was adopted as the severity of patients, namely "life-threatening" or
      "non life-threatening". RESULTS: 20% of all ED presentations of elderly patients
      were injury related compared to 39% of non-elderly. Compared to the non-elderly,
      elderly patients presenting to the ED with injury were more likely to be female,
      sustained injury from trauma unrelated to motor vehicle accidents (MVA) and
      requiring hospital admission as a result of "non life-threatening" injuries. They
      were less likely to have injuries from MVA or burns. The number of "life
      threatening" injury cases and mortality in both groups were similar. There was
      evidence that the number of ED presentations relating to injury is increasing in
      the elderly population. CONCLUSION: Elderly injury patients are a distinct group
      with distinctive demographics, mechanism of injury and outcomes. This information
      would be useful in the planning of injury prevention programs, with particular
      emphasis on elderly females and MVA-unrelated trauma.

PMID- 11951374
TI  - The unusual properties of effective blood substitutes.
AB  - Blood substitutes or oxygen carrying plasma expanders were originally formulated
      to simulate the transport properties of blood, particularly oxygen carrying
      capacity, viscosity, p50, and colloid osmotic pressure, under the hypothesis that
      blood is the most desirable fluid in volume restitution. However, changes
      introduced into the organism during hemorrhage adversely affect microvascular
      function due to reflex vasoconstriction which causes the fall of functional
      capillary density, and lowers tissue oxygenation, conditions that are not
      universally reversed with retransfusion of blood. The restoration of
      microvascular function is seldom complete upon retransfusion of blood. New
      formulations of hemoglobin molecules in solutions whose oncotic pressure is in
      the range of 60-100 mmHg, p50 is about 5 mmHg, viscosity 3-4 cP, and oxygen
      carrying capacity in the range of 4-7 g/dl equivalent hemoglobin deliver better
      microvascular function after resuscitation when compared to whole blood and
      oxygen carrying plasma expanders with transport properties similar to those of
      blood. The improved performance is in part due to the increased plasma viscosity
      which increases capillary transmural pressure which reverses capillary collapse
      induced during low perfusion pressures. High oncotic pressure reinforces this
      effect, since it brings more fluid into the circulation. Microvascular transport
      studies of the effects of resuscitation in shock show that functional capillary
      density is the primary determinant of survival, thus maintenance of an open and
      fully perfused microcirculation is more critical than insuring oxygen supply,
      since closed capillaries lead to the accumulation of slowly diffusing byproducts
      of metabolism which ultimately become toxic. The required combination of
      properties can be achieved by conjugating hemoglobin and polyethylene glycol.
      Resuscitation fluids based on hemoglobin containing vesicles may provide the next
      level of functional improvement in the formulation of volume restitution fluids
      since their biophysical properties can be specifically controlled through the
      inclusion of specialized compounds into the vesicles, and the formulation of the
      suspending medium.

PMID- 11951375
TI  - BP180 as the common autoantigen in blistering diseases with different clinical
      phenotypes.
AB  - Bullous pemphigoid antigen 180 (BP180, type XVII collagen) is a transmembrane
      hemidesmosomal glycoprotein of basal keratinocytes that spans the lamina lucida
      of the dermal-epidermal junction. Five autoimmune subepidermal blistering
      diseases are associated with an immune response to BP180, including bullous
      pemphigoid (BP), pemphigoid gestations (PG), cicatricial pemphigoid (CP), lichen
      planus pemphigoides (LPP), and linear IgA disease (LAD). The BP180 ectodomain
      consists of 15 interrupted collagen domains. The largest non-collagenous (NC) 16A
      domain is located next to the cell membrane. In BP, autoantibodies are directed
      to a tightly clustered set of epitopes located at the N-terminal 45 amino acids
      of the NC16A domain. However, some BP sera also react with other portions of the
      BP180 ectodomain or with the intracellular region of this protein. In PG,
      antibodies appear to exclusively recognize the immunodominant BP180 NC16A region.
      In CP, autoantibodies are directed to both the NC16A domain and the C-terminus of
      BP180 that projects into the lamina lucida/lamina densa interface of the dermal
      epidermal junction. In LPP, autoantibodies react with an epitope located at the C
      terminus of NC16A, that is not targeted by BP or PG sera. Finally, the epidermal
      97 kDa and the keratinoctye-derived 120 kDa autoantigens of LAD (LABD97 and LAD
      1, respectively) have recently been identified as portions of the BP180
      ectodomain. These observations demonstrate that different clinical phenotypes are
      associated with an autoimmune response to the same autoantigen yet the
      immunoglobulin subclass of the autoantibody and the epitope that is recognized
      may be different.

PMID- 11951376
TI  - Luminal acid elicits a protective duodenal mucosal response.
AB  - Measuring duodenal epithelial intracellular pH (pHi), blood flow and mucus gel
      thickness (MGT), we studied duodenal defense mechanisms in vivo so as to more
      fully understand the protective mucosal response to luminal acid. Exposure of the
      mucosa to physiologic acid solutions promptly lowered pHi, followed by recovery
      after acid was removed, indicating that acid at physiologic concentrations
      readily diffuses into, but does not damage duodenal epithelial cells. Cellular
      acid then exits the cell via an amiloride-inhibitable process, presumably sodium
      proton exchange (NHE1). MGT and blood flow increase promptly during acid
      perfusion; both decrease after acid challenge and are inhibited by vanilloid
      receptor antagonists or by sensory afferent denervation. Bicarbonate secretion
      does not increase during acid perfusion but increases following acid challenge.
      Inhibition of cellular alkali uptake by anion transport inhibitors lowers pHi,
      and increases mucosal injury, whereas inhibition of apical alkali secretion
      alkalinizes pHi and diminishes injury. These observations support the following
      hypothesis: luminal acid diffuses into the epithelial cells, lowering pHi. Acidic
      pHi increases the activity of a basolateral NHE, acidifying the submucosal space
      and increasing cellular alkali loading. The acidic submucosal space activates
      capsaicin receptors on afferent nerves, increasing MGT and blood flow. With
      continued acid exposure, a new steady state with thickened mucus gel, increased
      blood flow, and a higher cellular buffering power protects the mucosa from acid
      injury. After acid challenge, mucus secretion, blood flow and pHi return to
      normal, while bicarbonate secretion increases. Through these integrated
      mechanisms, the epithelial cells are protected from damage due to repeated pulses
      of concentrated gastric acid.

PMID- 11951377
TI  - Death from hypovolemic shock caused by perforation of duodenal ulcer in a patient
      with angiosarcoma of the scalp.
AB  - We report a case of an 86-year-old woman with angiosarcoma on the scalp, who died
      from hypovolemic shock caused by perforation of a duodenal ulcer. A purple-red
      macule was first noticed on her left temporal scalp, and over a 1-month period
      this macule rapidly grew to a 6 cm purple-red indurated plaque with hematomas.
      The diagnosis of angiosarcoma was made based on the clinical features and
      histopathological finding of the lesional skin. Perilesional injections of
      recombinant interleukin 2 (rIL-2) were followed by surgical resection of the
      lesion and graft repair. However, 5 months later, new hematomas appeared and
      increased in number and size to cover her cheek, left temporal scalp and around
      the grafted area. Electron-beam radiotherapy showed only a temporary effect and
      the skin lesions with spontaneous severe bleeding extended rapidly again toward a
      wide region of the left half of the scalp and cheek. The patient died of
      hypovolemic shock after acute abdominal pain with intestinal hemorrhage. The
      surgical pathology revealed the presence of a perforated duodenal ulcer which
      might have been the direct cause of hypovolemic shock.

PMID- 11951378
TI  - Use of nursing diagnoses and interventions in public health nursing practice.
AB  - PURPOSE: To determine the frequency of use of NANDA diagnoses and the Nursing
      Interventions Classification in care plans written by public health nurses (PHNs)
      in Orange County, CA. METHODS: Retrospective chart review. FINDINGS: The
      frequency pattern of nursing diagnoses and nursing interventions used in care
      plans is consistent with the scope of practice of the PHN, whose emphasis is on
      health promotion and disease prevention. CONCLUSIONS: The most commonly used
      diagnoses and interventions provide evidence of a core set of interventions
      useful for PHN practice. IMPLICATIONS FOR PRACTICE: Linking diagnoses and
      interventions allow PHNs to build a body of knowledge based on patient care and
      improve clinical decision-making process.

PMID- 11951379
TI  - Joining mind mapping and care planning to enhance student critical thinking and
      achieve holistic nursing care.

PMID- 11951380
TI  - The good news and the bad news.

PMID- 11951381
TI  - Ineffective family participation in professional care: a concept analysis of a
      proposed nursing diagnosis.
AB  - PURPOSE: To discuss the label, definition, defining characteristics, and related
      factors of a proposed nursing diagnosis, "ineffective family participation in
      professional care." DATA SOURCES: Published research articles, clinical
      handbooks, textbooks. DATA SYNTHESIS: Although a number of family-related nursing
      diagnoses exist, none really addresses the problems encountered if family members
      are unwilling or unable to participate in patient care. This is critical because
      the bulk of care occurs outside the hospital setting. CONCLUSIONS: A new nursing
      diagnosis, "Ineffective family participation in professional care" is needed.
      This diagnosis has been submitted to the Nursing Diagnosis Extension and
      Classification for consideration. PRACTICE IMPLICATIONS: With this diagnosis
      nurses could encourage family participation in care more effectively by focusing
      on assessment and interventions.

PMID- 11951382
TI  - Is healthcare security prepared for terrorism?
AB  - Programs for dealing with terrorism prior to the events of September 11, 2001 are
      inadequate for the new terrorist threat that may severely hamper a hospital's
      ability to render services. The article outlines areas of concern that must be
      addressed if hospitals are to fulfill their roles as major community resources in
      case of a terrorist event.

PMID- 11951384
TI  - Including Internet insurance as part of a hospital computer network security
      plan.
AB  - Cyber attacks on a hospital's computer network is a new crime to be reckoned
      with. Should your hospital consider internet insurance? The author explains this
      new phenomenon and presents a risk assessment for determining network
      vulnerabilities.

PMID- 11951385
TI  - Combatting domestic violence one person at a time.
AB  - How one hospital's security department works with other departments to assist
      employees involved in domestic violence.

PMID- 11951386
TI  - A terrorism response plan for hospital security and safety officers.
AB  - Security and Safety managers in today's healthcare facilities need to factor
      terrorism response into their emergency management plans, separate from the
      customary disaster plans and the comparatively recent security plans. Terrorism
      incidents will likely be security occurrences that use a weapon of mass
      destruction to magnify the incidents into disasters. Facility Y2K Plans can
      provide an excellent framework for the detailed contingency planning needed for
      terrorism response by healthcare facilities. Tabbed binder notebooks, with
      bulleted procedures and contact points for each functional section, can provide
      security and safety officers with at-a-glance instructions for quick 24/7
      implementation. Each functional section should focus upon what activities or
      severity levels trigger activation of the backup processes. Network with your
      countywide, regional, and/or state organizations to learn what your peers are
      doing. Comprehensively inventory your state, local, and commercial resources so
      that you have alternate providers readily available 24/7 to assist your facility
      upon disasters.

PMID- 11951388
TI  - Performance improvement in the JCAHO environment of care.
AB  - Using security management to demonstrate performance improvement for JCAHO can be
      a viable option. The article illustrates how a program for reducing theft became
      the basis for demonstrating performance improvement.

PMID- 11951387
TI  - Security management performance improvement 2001.
AB  - The author discusses how a large healthcare facility has improved security
      management practices and increased security presence. He provides the results of
      a survey report, relates how the recommendations were prioritized and
      implemented, and also provides a progress summary.

PMID- 11951389
TI  - Private security and municipal police: an atmosphere of cooperation.
AB  - The author, a former deputy chief of police, discusses the importance of mutual
      cooperation between private and contract security and local police agencies. He
      discusses the steps he took to forge a bond between his hospital security staff
      and the local police department.

PMID- 11951390
TI  - Meeting the major threats to hospital security within a budget.
AB  - Despite the need to meet growing threats within a facility, cutbacks in hospital
      income and the resultant budget restraints continue to challenge hospital
      security departments to do more with less. This article reports on a number of
      approaches being employed to successfully meet the challenges.

PMID- 11951391
TI  - Hospital security investigations.
AB  - The author discusses the importance of investigation in the hospital setting and
      how to conduct a good investigation. A security investigation in the healthcare
      field, he says, may be quite different from one in law enforcement.

PMID- 11951392
TI  - Taking parking protection to the next level.
AB  - Because of neighborhood crime problems, the Johns Hopkins Medical Institutions
      decided to undertake security improvement projects aimed at enhancing
      security/safety at the campus. This article focuses on the security changes and
      improvements to the parking structures and surface parking lots that have helped
      make the campus a safer place for patients, visitors, and staff.

PMID- 11951393
TI  - What hospital security should be doing now to better prepare for future terrorist
      activity.
AB  - This country is a battlefield in a war in which hospital security professionals
      will play a critical role. The author presents the advice and recommendations of
      experts in terrorism and healthcare to assist such professionals in meeting their
      new responsibilities.

PMID- 11951394
TI  - Starting a canine program.
AB  - If it is done properly, a program of canine patrols in a healthcare setting can
      produce a number of benefits, not the least of which is a decline in criminal
      activity. In this article, the author shares his experiences in developing and
      implementing a successful program.

PMID- 11951395
TI  - Occupational assault among community care workers.
AB  - The author presents the findings of a study that attempted to analyze the
      frequency, trend, and pattern of workplace assaults among community care workers
      who provide care for severely emotionally and behaviorally disturbed children in
      a state government agency in Australia between 1997 and 2000. He identifies the
      high risk groups and discusses activities for prevention opportunities.

PMID- 11951396
TI  - Hospital liability for assault on patients.
AB  - The issue of a hospital's duty to adequately protect its patients, goes beyond
      the duty to provide good medical care. Since 1907, courts have been making
      decisions on hospital liability for injuries to patients by other patients and
      third parties. In this article, the authors, attorneys, review a number of these
      cases and present risk management strategies to help healthcare organizations
      address such issues before they occur.

PMID- 11951397
TI  - Curing privacy problems: HIPAA/Healthcare.
AB  - A New Jersey-based health system began its HIPAA compliance project in late 1999,
      several years away from the deadline. The article discusses what the organization
      has done and is doing, including launching an education initiative, assessing
      existing privacy and security policies, upgrading complete security services, and
      designing a HIPAA project management tool.

PMID- 11951398
TI  - More, or more effective, education?

PMID- 11951399
TI  - A practical approach to nutritional support for patients with advanced cancer.
AB  - Palliative care can last from a few days to months and, in some cases, years.
      Consequently the nutritional needs of palliative care patients also vary, as does
      the extent to which nutrition intervention is pursued. Anorexia and cachexia are
      common side-effects of advanced cancer. They are characterized by physical
      depletion of the patients and an emotional drain on them, their families and
      carers. Pulling together the practical aspects of nutrition support and the
      emotional and social significance of food requires a skillful practitioner; an
      experienced dietitian can be a valued member of the palliative care team. This
      article examines the role of nutrition support in the palliative care setting,
      focusing upon practical advice including food modification, the use of oral
      supplements and enteral feeding.

PMID- 11951400
TI  - A study of family carers of people with a life-threatening illness. 2:
      Implications of the needs assessment.
AB  - This is the second of two articles that consider the findings of a Carers'
      Assessment of Difficulties Index (CADI) (Nolan et al, 1998) delivered in a
      palliative care context. It analyses the implications of these findings for
      practitioners concerned with the delivery of palliative care to such carers and
      their families. The development of support strategies and services addressing
      their needs are also presented against a backdrop of transactional stress theory.
      For people new to caring, recommendations for the local service include early
      intervention through informational support and validation of their emotional
      responses to caring; for longer-term carers they include assistance with
      cognitive reappraisal of the stressfulness of caring and regular 'respite' and
      socializing opportunities. These are taking place in a political climate that
      finally recognizes the contribution and value of carers (Department of Health,
      1999). The research behind these carer identity and recognition initiatives aims
      to apply the spirit of public recognition and practical wisdom of palliative care
      expertise by responding sensitively to the specific needs of carers of people
      with a life-threatening illness.

PMID- 11951401
TI  - Support needs of brain tumour patients and their carers: the place of a telephone
      service.
AB  - Although the survival rate for many cancers has improved over the past two
      decades this has not happened for most patients with a primary malignant brain
      tumour. Numbers of patients diagnosed with this condition each year are small,
      and as expertise is often very limited, information, advice, and support can be
      difficult for patients and carers to access. The role of the appropriately
      trained nurse in meeting these needs has been well researched and published
      literature supports the development of such roles. The use of the telephone for
      providing information and support has become more common in recent years. The
      Regional Cancer Centre in the west of Scotland covers a wide geographical area
      and it was considered appropriate to initiate such a service for patients and
      their carers in that area to provide easier access to specialist knowledge and
      advice and subsequently improve continuity of care. This article discusses some
      of the support and informational needs of patients with brain tumours and their
      carers, which highlight reasons for introducing the telephone service in this
      cancer centre. The results of a 2-year audit of the service will be also be
      presented.

PMID- 11951402
TI  - Caring in palliative nursing: competency or complacency?
AB  - Caring is an attribute of palliative nursing that is assumed to be fundamental.
      However, as the sophistication of palliative care increases, the liberal art of
      caring has become submerged under the weight of medical and pharmacological
      sciences. The nursing profession defends caring as the essence of its practice
      yet caring work in the palliative environment receives relatively little
      attention in research or in literature generally. Although it is accepted that
      nurses' caring work sometimes involves intimate and private aspects of patient
      care, the value and positive outcomes of caring should not remain hidden.
      Palliative nurses have special but tentative opportunities to prove the value of
      caring and define the complexity of caring work. This article argues that nurses
      need to reclaim the caring ethic and demonstrate its worth.

PMID- 11951403
TI  - Metaphor: exploring its origins and therapeutic use in death, dying and
      bereavement.
AB  - Metaphor is a commonly used and powerful language device for expressing complex
      thoughts or feelings. This exploratory qualitative study examined the sources and
      function of metaphor in relation to death, dying and bereavement. The study
      involved focus group discussions and follow-up questionnaires with professionals
      from three different contexts (nursing, hospice and bereavement counselling), and
      gave rise to a number of interesting observations. The results have implications
      for professional carers, particularly those working in dying and bereavement
      contexts, in relation to facilitating the use of metaphor to enhance the quality
      of communication. Suggestions are made for further research.

PMID- 11951404
TI  - An overview of chemotherapy-induced peripheral sensory neuropathy, focusing on
      oxaliplatin.
AB  - When treating patients for metastatic cancer, there is always a balance between
      the benefits of treatment and resulting side-effects. Peripheral sensory
      neuropathy (PSN) is a side-effect of many anticancer agents used in routine
      practice. Oxaliplatin is a relatively new agent currently licensed in over 50
      countries including France, Germany and the UK for the treatment of metastatic
      colorectal cancer. Although it is a new agent, it is from the same family of
      drugs as cisplatin, an agent that has been used for many years. PSN is the most
      commonly discussed side-effect associated with oxaliplatin. Oxaliplatin-induced
      PSN is characterized by two distinct syndromes: a transient acute dysaesthesia
      and a cumulative distal neurotoxicity. Importantly, both are generally reversible
      after stopping treatment. Oxaliplatin-induced acute PSN is triggered and
      exacerbated by cold and can be greatly reduced in affected patients simply by
      avoiding cold conditions. Oxaliplatin-induced cumulative PSN may also be managed
      by temporary cessation of treatment.

PMID- 11951412
TI  - Complications of miniplate osteosynthesis in the treatment of mandibular
      fractures.
AB  - Miniplate osteosynthesis with 2.0-mm screws is being increasingly utilized in the
      treatment of mandibular fractures, midface fractures, zygomatic fractures,
      orthognathic surgery, and in craniomaxillofacial surgery. It enables better
      anatomic reduction, better stability of fracture lines, quick recovery and return
      of function. To examine complications related to its use, data were compiled from
      the preoperative, immediately postoperative, and 6-months' postsurgery
      examinations of 143 patients with isolated mandibular fractures. Sixteen of the
      patients (11.2%) presented with postoperative complications that were related to
      the miniplate system. The authors' experience and data support the theory that
      the complication rate is related more to the surgical approach and technique than
      to the time elapsed between injury and operation.

PMID- 11951413
TI  - Incidence and type of cervical spine injuries associated with mandibular
      fractures.
AB  - The incidence of facial fractures accompanied by spinal injuries, while low, is
      of significant concern to the craniomaxillofacial surgeon. There are conflicting
      reports on the association between facial fractures and concomitant spinal
      damage. This retrospective study of 424 patients with mandibular fractures
      examines the relationship of mandibular fractures and concomitant spinal
      injuries. The incidence of concurrent mandibular and cervical fractures was 2.6%,
      predominantly associated with motor vehicle accidents. The purpose of this study
      is to examine the incidence of cervical spine injury associated with mandibular
      fractures, in order to improve the diagnosis and treatment of spinal injury
      associated with mandibular fractures.

PMID- 11951414
TI  - Treatment and prevention of alveolar fractures and related injuries.
AB  - Dentoalveolar trauma does not pose a significant morbid risk for the trauma
      patient. However, the long-term consequences of mismanagement can be devastating.
      Early, correct diagnosis, and appropriate referral of these injuries can affect
      the success of treatment. Failure to recognize or obtain appropriate consultation
      can result in premature tooth or alveolar bone loss, resulting in problematic
      prosthetic rehabilitation. The purpose of this article is to review the concepts
      of recognition, management, and prevention of dentoalveolar trauma. In situations
      where the possibility of trauma is likely, such as in athletics, dentoalveolar
      and related fractures can be prevented through the use of mouthguards fabricated
      by health care professionals.

PMID- 11951416
TI  - Midface reconstruction with titanium mesh and hydroxyapatite cement: a case
      report.
AB  - Reconstruction of the midface following trauma generally involves the simple
      assemblage of the existing bony fragments with the usage of miniplate
      osteosynthesis. Fractures of the maxilla are of significant functional as well as
      aesthetic importance. Occasionally, reestablishment of the bony structure is not
      possible without the concomitant use of bone grafts to replace areas where bone
      loss is present due to extensive comminution. Calvarial bone grafts are often
      used; however, they are not ideal, due to donor site morbidity, resorption, and
      difficulty in contouring the grafts to the curves of the face. This article will
      review a case of severe midfacial trauma in which a significant portion of the
      comminuted midface was successfully reconstructed with titanium mesh and
      hydroxyapatite cement.

PMID- 11951417
TI  - Ultrasonographic versus conventional diagnostic procedures in dislocated
      subcondylar mandibular fractures.
AB  - In patients with severe craniomaxillofacial trauma, immediate attention is
      directed primarily to the early diagnosis of cervical spine injuries,
      intracranial injuries, respiratory difficulties, and vascular compromises.
      Diagnostic studies, such as computed tomography scans, are sometimes not useful
      for the evaluation of mandibular fractures, since cuts are performed too
      superiorly. The plane radiographs obtained in emergency settings are frequently
      of minimal diagnostic value. Fractures of the mandibular symphysis, body, and
      angles are easily identified clinically; subcondylar fractures, however, are not
      directly accessible for clinical examination. The evaluation of suspected
      dislocated subcondylar fractures with the aid of ultrasonography is reliable,
      highly sensitive and specific, and cost-effective.

PMID- 11951415
TI  - Open reduction of subcondylar fractures via an anterior parotid approach.
AB  - Visualization of subcondylar fractures is limited, and rigid fixation technically
      difficult, employing standard open surgical techniques--especially when the
      condyle is displaced out of the glenoid fossa. The majority of condylar neck
      fractures are treated by closed reduction with maxillomandibular fixation, to
      obviate the potential for permanent injury to the facial nerve. The technique
      described employs an anterior parotid, two-layer, sub-SMAS (superficial musculo
      aponeurotic system) approach via a rhytidectomy incision that reliably identifies
      and preserves the neural elements and provides direct access to the pericondylar
      region. The thirteen patients presented here exhibited satisfactory functional
      and aesthetic results. Complications included temporary nerve palsies, plate
      fractures, and a hematoma.

PMID- 11951419
TI  - Rigid internal fixation of fractures of the craniomaxillofacial skeleton has
      become the "standard of care.".

PMID- 11951418
TI  - Transnasal canthoplasty.
AB  - The reconstruction of a traumatic telecanthus, particularly the repositioning and
      securing of the medial canthal tendon, presents a challenge to the reconstructive
      surgeon. The adequate positioning of the medial canthal tendon for proper
      intercanthal distance, and apposition of the lid to the globe, is the cornerstone
      of a successful reconstruction. The authors have developed a technique for
      transnasal canthoplasty that is fast, relatively easy, and safe. Transnasally, a
      16-gauge spinal needle is introduced over a preplaced K-wire using a 4-0 Bunnell
      stainless wire suture (Ethicon, Somerville, NJ). The medial canthal tendon is
      lassoed, secured, and then fixed to the contralateral nasal bone. Six patients
      have undergone this technique to date. The authors believe this procedure offers
      an improvement to existing methods.

PMID- 11951420
TI  - Traumatic cranial defects reconstructed with the HTR-PMI cranioplastic implant.
AB  - Titanium mesh, polymethyl methacrylate application, and autogenous bone grafting
      have been used to reconstruct traumatic cranial defects, with varying success. A
      more recent technique utilizing hard tissue replacement-patient matched implants
      (HTR-PMIs) involves the production of a cranioplastic implant using three
      dimensional computed tomography imaging. It has proven less time-consuming and
      provides an excellent cosmetic result for the patient. The authors present two
      case reports using this technique to correct traumatic cranial defects. Both
      patients exhibited satisfactory results and no postoperative complications. The
      authors believe this relatively new technique represents an advance in the
      management of large cranial defects.

PMID- 11951421
TI  - Association between orbital fracture location and ocular injury: a retrospective
      study.
AB  - BACKGROUND: Orbital fractures are frequently accompanied by ocular injury. Any
      findings that provide information for diagnosing a concurrent ocular injury
      should improve patient care. A greater incidence of severe ocular injury with
      certain fracture types was hypothesized, based on orbital wall thickness.
      METHODS: A retrospective review of 87 consecutive patients (107 fractured orbits)
      was performed by the Ophthalmology Department of an urban Level 1 trauma center.
      RESULTS AND CONCLUSIONS: Severe injuries were associated with orbital apex
      fractures (p = 0.00001), with lateral wall fractures (p < 0.04), and with Le Fort
      Type III fractures (p < 0.02). Moderate injuries were associated with isolated
      orbital floor fractures (p < 0.01). Apex, lateral wall, and Le Fort Type III
      fractures have a greater association with severe ocular injuries than other
      fracture types.

PMID- 11951423
TI  - Management of orbital-sinus foreign bodies.
AB  - Orbital-sinus foreign bodies traverse the orbit and lay, at least partially,
      within the paranasal sinuses. Most of these injuries occur as a result of facial
      trauma. In most cases, history alone is not sufficient to rule out a retained
      foreign body. Early magnetic resonance imaging is necessary to evaluate the full
      extent of injury. Since these foreign bodies may cause a severe orbital infection
      and threaten the patient's vision, surgical removal is recommended. Endoscopic
      sinus surgery provides a safe and effective approach for extraction of these
      foreign bodies that can be used alone or in conjunction with other surgical
      approaches. The case of an orbital-sinus foreign body is presented together with
      a comprehensive approach for diagnosis and management of this type of injury.

PMID- 11951422
TI  - Stereolithography: a historical review and indications for use in the management
      of trauma.
AB  - BACKGROUND: Stereolithography (SL) is a new adjunct for treatment planning in
      complex maxillofacial trauma. It uses an argon/ion laser to polymerize acrylic
      resin models of reformatted computerized tomographic radiographs. SL provides
      superior anatomical detail and translucency, and it can be sterilized and
      transported to the operative field, if necessary. DISCUSSION: A review of the
      historical development of SL technology is presented, along with three clinical
      cases, showing the advantages of SL models in the treatment of patients with
      complex maxillofacial trauma. CONCLUSION: SL technology provides superior
      understanding of anatomic relationships, the ability to perform presurgical
      simulation of the proposed procedure, preoperative adaptation of biomaterials,
      decreased time in the operating room and associated patient morbidity, and
      improved residency training and patient education. The primary disadvantages of
      SL are availability and cost.

PMID- 11951424
TI  - Evolution of the extracranial approach for repair of CSF leaks: review of the
      literature and clinical cases.
AB  - The management of cerebrospinal fluid rhinorrhea changed with the advent of
      endoscopes in the early 1990s. The majority of repairs are now approached
      endoscopically, i.e., extracranially. This article reviews the evolution of the
      extracranial approach, as reported in the literature, concluding with the
      experience of the authors. A total of 15 patients were treated by the primary
      author since 1987; an open external ethmoid approach was utilized in 3 patients,
      and an endoscopic approach was used to treat 12 patients. The success rate with
      the external ethmoid approach was 100%; with the endoscopic approach, the primary
      success rate was 75% (9/12). There were 3 failures: One was due to a graft
      shrinkage; another was secondary to inadequate visibility; and the reason for the
      third was unclear. Eventually, all three were successfully repaired. Based on
      this experience, cerebrospinal fluid rhinorrhea can be successfully managed via
      an extracranial approach 75% of the time.

PMID- 11951425
TI  - Usefulness of endoscopy in craniofacial trauma.
AB  - To determine the extent of endoscopy utilized in craniofacial trauma, a
      questionnaire was mailed to 400 surgeons in the United States. A 40% response was
      obtained; 21.3% of the surgeons stated that they had used endoscopy to treat
      facial fractures; 33% of them had been in practice for 6 to 10 years, and 47% of
      those who had used endoscopy in craniofacial trauma were in full-time private
      practice. In facial fractures, endoscopes were used primarily to treat Le Fort
      fractures (55.9%), followed by zygomatic arch fractures (52.9%). Lack of
      accompanying instrumentation, such as appropriate drills, to use with the
      endoscope via small openings was cited as a significant problem; 46% of the
      respondents were unable to resolve it. Most respondents (55.6%) felt that if
      proper accompanying instrumentation were to be developed, endoscopes would become
      an integral component in the management of craniofacial trauma.

PMID- 11951426
TI  - Treatment of cranial vault fractures: recent trends toward a more conservative
      approach.
AB  - A number of aspects in historical teaching regarding the indications for
      operative treatment of fractures of the cranial vault have been recently
      challenged. Several contemporary studies have reported excellent results by
      employing a more conservative approach regarding the treatment of displaced
      fractures of the skull. Improvements in the diagnosis of injuries by computerized
      tomography (CT) scanning, antibiotic therapy, and the ability to rapidly transfer
      patients to neurosurgical care have allowed neurosurgeons to treat many of these
      injuries outside the operating room with local irrigation, debridement, and
      simple closure of the wound. Cosmetic deformities of the skull are one of the few
      absolute indications for surgical therapy. This article reviews the recent
      literature regarding skull fractures of the cranial vault and discusses the
      indications for surgical therapy in these patients and cases where a more
      conservative approach may be utilized.

PMID- 11951428
TI  - Endoscopic exploration of the orbital floor: a technique for transantral grafting
      of floor blowout fractures.
AB  - A cadaveric study was conducted with a twofold purpose--to perform diagnostic
      transantral endoscopy in pure blowout fractures of the orbital floor and to
      attempt restoration of bony defects in the orbital floor using the endoscope.
      Endoscopic visual access of the orbital floor allows precise determination of the
      fracture size and the presence and extent of entrapped periorbital fasciae. A
      bony defect was created surgically in the orbital floor of 6 fresh cadaver heads,
      and a split-thickness calvarial bone graft and an alloplast were used to repair
      the orbital floor. Grafting of the orbital floor with endoscopic visual access
      was successful, and the potential risks associated with the traditional eyelid
      incisions were minimized. The anatomic course of the infraorbital nerve was
      observed and protected. The study confirmed that endoscopy could be used
      successfully in obtaining visual access to the orbital floor.

PMID- 11951427
TI  - Management of frontal sinus fractures with posterior table involvement: a
      retrospective study.
AB  - Management of frontal sinus fracture has been a matter of debate. Combined
      fractures of the anterior and posterior walls have been managed by various
      techniques, including observation, open reduction and internal fixation,
      ablation, obliteration, and, most recently, cranialization. The earlier
      techniques have met with frequent complications, including sinusitis,
      mucopyocele, cerebrospinal fluid leak, meningitis, and brain abscess, along with
      various chronic pain symptoms. Cranialization of the frontal sinus was first
      introduced for injuries of both walls with intracranial penetration. From 1990 to
      1996, frontal sinus fractures of 11 patients (10 men and 1 woman) were treated
      using the cranialization procedure. Based on patient history, clinical findings,
      radiographic diagnoses, operative techniques, and follow-ups of these patients
      the authors conclude that cranialization of the frontal sinus is a safe and
      effective method of treating posterior table frontal sinus fractures.

PMID- 11951429
TI  - Options for immediate reconstruction of the traumatized temporomandibular joint.
AB  - The management of condylar fractures is one of the most controversial topics in
      the repair of the maxillofacial skeleton. An extensive volume of literature
      exists describing the various indications for a specific treatment of this
      injury. This article outlines the absolute and relative indications for an open
      procedure and describes three different modalities for the immediate
      reconstruction of the temporomandibular joint system. Three different case
      reports are used to illustrate the respective procedures--replacement of the
      temporomandibular joint with autologous rib graft, replacement of the
      temporomandibular joint with an alloplast, and vertical ramus osteotomy for
      repositioning of the condylar stump. The discussion section reviews the findings
      and preferences of various treatment modalities described in the literature,
      along with the advantages and disadvantages.

PMID- 11951430
TI  - Frontobasilar blast injuries: access and treatment.
AB  - Blast injuries involving the frontobasilar region and orbit can present difficult
      evaluation and treatment challenges. This article presents the surgical treatment
      of four patients presenting with blast-type injuries involving the central
      periorbital region and anterior skull base. Three of these were the result of
      close-range gunshot wounds, and one was caused by an avulsive penetrating tree
      branch injury during a motor vehicle accident. All four patients underwent
      frontal craniotomy for exposure to repair significant intracranial injuries.
      Following intracranial repair of dural and brain injuries, anterior cranial fossa
      reconstruction was performed. In two of these patients, elective supraorbital
      osteotomies were performed to allow improved access to the posterior aspect of
      the anterior skull base. The healing period of all four patients has been without
      complications relative to the anterior fossa injuries.

PMID- 11951431
TI  - Facial fractures and related injuries: a ten-year retrospective analysis.
AB  - A retrospective analysis of 828 patients with significant midface or mandibular
      fractures was undertaken to illustrate the multisystem nature of traumatic
      injuries associated with fracture of the facial skeleton, covering the period
      from 1985 to 1994. Special emphasis was placed on determining associated injuries
      sustained as well as epidemiological information. The experience presented
      differs from other large series in the literature in that the predominant
      mechanism of injury is motor vehicle accidents (67%) rather than assaults. Of the
      patients reviewed, 89% sustained significant associated injuries. Closed head
      trauma with documented loss of consciousness was noted most frequently (40%),
      followed by extremity fractures (33%), thoracic trauma (29%), and traumatic brain
      injuries (25%). Only 11% of patients sustained facial fractures without
      concomitant injury.

PMID- 11951432
TI  - Skull-base trauma: neurosurgical perspective.
AB  - Trauma to the cranial base can complicate craniofacial injuries and lead to
      significant neurological morbidity, related to brain and/or cranial nerve injury.
      The optimal management involves a multidisciplinary effort. This article provides
      the neurosurgeon's perspective in management of such trauma using a 5-year
      retrospective analysis of patients sustaining skull-base trauma. The salient
      features of anterior and middle skull-base (temporal bone) trauma are summarized,
      and the importance of frontal basilar trauma as well as brain injury is evident.
      With these injuries, all cranial nerves (except 9 to 12) are at risk; the
      olfactory nerve and the facial nerve are the first and second, respectively, to
      sustain injuries. This retrospective analysis provides a better understanding of
      cranial base trauma and its management. It emphasizes the multifaceted nature of
      such trauma and the need to recognize anterior skull-base complications,
      including cerebrospinal fluid leak and brain injury.

PMID- 11951433
TI  - Optic nerve size in traumatic optic neuropathy.
AB  - The assessment of traumatic optic neuropathy in a neurologically impaired patient
      is difficult, and the size of the optic nerve has been suggested as a potential
      adjunct in differential diagnosis. This controlled retrospective study was
      designed to evaluate the size of the optic nerve involved in traumatic optic
      neuropathy when compared to the optic nerve in the noninjured eye. Maxillofacial
      computerized tomographs of 22 patients were examined; intraorbital optic nerve
      diameter was measured on injured and noninjured sides, with the examiner unaware
      of the side of injury. No statistically significant difference in size was found
      between the traumatized optic nerves and those that remained intact. The authors
      have concluded that the size of the optic nerve is not a reliable predicator of
      the presence or absence of traumatic optic neuropathy when measured with
      computerized tomograph scans.

PMID- 11951434
TI  - Comparison of transconjunctival versus subciliary approaches for orbital
      fractures: a review of 60 cases.
AB  - The increasing emphasis on open reduction in the management of orbital fractures
      has led to an extensive debate as to which approach provides adequate exposure
      for these fractures. This retrospective study compares the exposure provided and
      the rate of complications between transconjunctival and subciliary incisions for
      orbital rim and floor fractures. The charts of 55 patients with orbital
      fractures, treated with open reduction and internal fixation, were reviewed. A
      total of 30 subciliary and 30 transconjunctival incisions had been performed, and
      the adequacy of exposure as well as intraoperative and postoperative complication
      rates were compared. The authors found a higher rate of complications with the
      subciliary approach and, therefore, advocate the use of a transconjunctival
      incision for the management of orbital fractures.

PMID- 11951435
TI  - Endoscopic repair of posttraumatic enophthalmos using medial transconjunctival
      approach: a case report.
AB  - A blowout fracture of the medial orbital wall should be suspected when
      periorbital trauma results in epistaxis, orbital hemorrhage, horizontal
      dysmotility or dystopia of the globe, and/or orbital emphysema. Large medial
      orbital wall blowout fractures are frequently complicated by posttraumatic
      enophthalmos. Clinicians should consider a medial transconjunctival approach for
      repair of these fractures when surgical repair is indicated by a comprehensive
      clinical and radiologic orbital evaluation. Excellent cosmetic and functional
      results can be achieved through the use of an extended transcaruncular incision,
      rigid endoscope, and high-density porous polyethylene implant placement. The
      technique can be used in the early, delayed, and late stages of medial orbital
      wall blowout fracture repair. The technique can be used alone in isolated medial
      orbital wall fractures or combined with other craniofacial approaches.

PMID- 11951436
TI  - The use of osseointegrated implants in craniofacial trauma.
AB  - The objective in treating patients with injuries sustained in craniofacial trauma
      is to reinstate preinjury facial projection and function. The capability of
      providing spatially related facial reconstruction is predicated on basic
      craniofacial surgical principles, generally accepted as the standard of care.
      These principles include early surgical intervention, immediate bone grafting,
      and the use of internal rigid fixation. The introduction of osseointegrated
      dental implants has significantly improved the overall reconstruction of patients
      with cranio-maxillofacial injuries, including soft tissue repair and cosmetic
      surgery. The purpose of this article is to review the utilization of dental
      implants in the context of maxillofacial trauma, using three cases to document
      the clinical procedure.

PMID- 11951437
TI  - Posttraumatic scar revision: a review and case presentation.
AB  - Scar revision is a well-established procedure, but the achievement of satisfying
      long-term results may present a challenge. An appropriate initial management of
      wounds is of importance, since it has a role in determining the degree of
      revision required postoperatively. In addition to the conventional treatment and
      maturation of the scar tissue, a combination of procedures are now available
      which may alter the appearance of the final scar. Scar revision, followed by
      wound care that consists of silastic sheeting, steroid injection, and laser skin
      resurfacing with carbon dioxide laser (CO2), may be used as adjuncts to achieve
      camouflage of facial scars. Two case reports are presented to document the
      procedure, followed by treatment evaluation and protocol.

PMID- 11951438
TI  - The transcaruncular approach in repair of orbital fractures: a retrospective
      study.
AB  - The use of a transcaruncular approach to the medial orbit provides excellent
      exposure of the medial wall and avoids a cutaneous scar. This article presents
      the clinical procedure in a retrospective study of 8 patients. An incision
      through the caruncle, combined with an incision along the inferior conjunctival
      fornix, provides wide exposure of the medial and inferior orbit. Traumatic
      fractures of the orbit typically involve the thin bone of the medial and inferior
      walls. The clinical history and findings in 8 patients with bony orbital
      fractures are presented. In each case, surgical repair was based on the
      transcaruncular approach. Results of postoperative evaluation (range of 24 days
      to 32.5 months) are described, with a mean follow-up period of 8.5 months. The
      authors conclude that the transcaruncular approach is well suited to surgical
      repair of blow-out fractures to the medial orbit, in combination with an inferior
      transconjunctival incision.

PMID- 11951439
TI  - Orbitocraniofacial gunshot wounds: craniofacial reconstruction and preparation of
      the anophthalmic socket.
AB  - This article is a retrospective clinical and radiographic analysis of four
      patients who survived high caliber orbitocraniofacial gunshot injuries. Early
      multidisciplinary craniofacial reconstruction included repair of comminuted
      orbital fractures with multiple autogenous bone grafts and/or porous polyethylene
      implants, enucleation, and insertion of a hollow silicone sphere as an
      anophthalmic socket implant. Migration of the silicone implant occurred in one
      case, requiring replacement with an autogenous dermis fat graft. There were no
      cases of extrusion or infection. Socket motility remained limited in all cases,
      despite reapposition of the extraocular muscles. In two cases with autogenous
      bone grafts along the orbital roof, there was no radiographic evidence of graft
      resorption after three years. Soft tissue volume deficiency and superior sulcus
      deformity developed in the three cases which were followed for more than six
      months. Despite these limitations, all four patients are wearing comfortable
      ocular prostheses. The postoperative results support immediate preparation of the
      anophthalmic socket after craniofacial reconstruction of these injuries.

PMID- 11951440
TI  - Management of frontal sinus fractures.
AB  - Frontal sinus fractures have been reported in 2 to 12 percent of all cranial
      fractures and, according to one study, in 8 percent of all facial fractures.
      Although immediate frontal bone reconstruction is not universally accepted, it is
      rapidly becoming the standard of care in treating cranial facial fractures, even
      in the face of gross contamination. This article presents a historical overview
      of fracture management, a review of the relevant anatomy, and a discussion of
      appropriate management principles. Three case studies are presented to
      demonstrate appropriate techniques for the management of frontal sinus fractures.

PMID- 11951441
TI  - Repair of mandibular fractures using the 2.0 mm system. A review.
AB  - The mandible is a commonly injured facial bone with mandibular fractures
      occurring 3 times more frequently than those in the zygoma. Requirements for
      repair vary with the type of fracture, the location of the fracture, and the
      condition of the teeth and bone. Repair of the mandible is complicated by the
      complex range of function of the mandible. This article presents a brief,
      historical overview of techniques and systems that have been used for fracture
      stabilization. The authors report on the results of a study in which the 2.0 mm
      plate was used to repair 89 fractures. The use of 2.0 mm mandibular plates
      appears to provide adequate stability for patients with healthy bone and minimal
      comminution.

PMID- 11951442
TI  - Comprehensive management of pan-facial fractures.
AB  - In the last 20 years, the management of pan-facial injuries has progressed to the
      point where immediate treatment using open reduction with rigid fixation is now
      the standard of care. After discussing the historical progression of treatments,
      the authors present a plan for treatment of craniofacial injuries based on the
      use of incisions that expose the four areas of the face: the frontal area, upper
      midface, lower midface and occlusion, and the basal mandibular area. According to
      the authors, five incisions permit access to the entire anterior craniofacial
      skeleton: the coronal, lower eyelid, upper and lower gingival-buccal-sulcus, and
      the preauricular-retromandibular. Through these incisions, the facial buttresses
      can be accessed to allow reduction and rigid fixation of facial fractures.

PMID- 11951443
TI  - Craniofacial trauma in children.
AB  - Craniofacial trauma is relatively uncommon in children, but the potential
      involvement of the structures at the base of the skull and the intracranial space
      makes it important for physicians to understand the potential dangers presented
      by such injuries. This report delineates the different types of injury that can
      damage the upper facial skeleton and the brain of a child. The author reviews
      initial management and diagnosis of such injuries and examines the approach to
      definitive reconstructive surgery using three case studies as examples for
      discussion.

PMID- 11951444
TI  - External rhinoplasty approach for repair of posttraumatic nasal deformity.
AB  - Up to 50% of patients who have suffered a nasal fracture may seek reconstructive
      surgery because they are dissatisfied with their appearance and/or ability to
      breathe. Distortion of native anatomy and dissection planes increases with
      severity of the injury. The external rhinoplasty approach is a biologically sound
      technique that offers several advantages over endonasal access for the repair of
      complex nasal deformities. In 30 consecutive posttraumatic rhinoplasty cases over
      a 2-year period, 27 (90%) patients underwent correction of their deformities via
      the external rhinoplasty approach. No technique-specific sequelae were
      encountered, and all patients were satisfied with their respective result and the
      healing of the transcolumellar incision. This article reviews the advantages,
      disadvantages, and contraindications of the external rhinoplasty approach in the
      posttraumatic patient.

PMID- 11951445
TI  - Parotid salivary fistula secondary to external pin fixation: case report.
AB  - Although the use of rigid fixation techniques has become widespread for the
      treatment of mandible fractures, indications still remain for the utilization of
      biphasic external pin fixation in patients who suffer cranio-maxillofacial
      trauma. The treatment of continuity defects of the mandible secondary to avulsive
      injuries or ablative surgery is a primary indication for the utilization of
      biphasic external pin fixation. The placement of biphasic external pins requires
      an understanding of the surgical anatomy surrounding the mandible. In this
      article, the authors discuss the indications for, contraindications for, and
      complications associated with the use of biphasic external pin fixation, describe
      the procedure, and present a case report of a patient with parotid salivary
      fistula secondary to the placement of external pin fixation.

PMID- 11951446
TI  - Facial soft tissue resuspension following upper facial skeletal reconstruction.
AB  - Only recently has the importance of precise soft tissue repositioning to extend
      access to the cranio-maxillofacial skeleton been appreciated. The authors
      examined 39 patients who underwent procedures requiring a combination of coronal,
      lower lid, and buccal sulcus incisions to provide maximal skeletal exposure of
      the periorbital, zygoma, and maxillary regions; the patients were examined both
      prior to and following the use of soft tissue resuspension techniques. In this
      article, the authors demonstrate the need for soft tissue resuspension in
      procedures of the upper facial skeleton when large areas of soft tissue have been
      mobilized for the purpose of exposure. They suggest a difference in soft tissue
      positioning following the degloving approaches to the upper facial skeletal area
      when intentional soft tissue resuspension is undertaken.

PMID- 11951447
TI  - The role of the nasofrontal duct in frontal sinus fracture management.
AB  - The surgical management of frontal sinus fractures is controversial in cranio
      maxillofacial trauma, due to the complexity of the anatomy surrounding the
      frontal sinus and the potential for devastating complications if these fractures
      are improperly treated. The critical factor in the evaluation of the frontal
      sinus is the status of the nasofrontal duct, which must be patent if a decision
      is made to preserve the sinus. Compromise of the nasofrontal duct warrants the
      removal of the frontal sinus as a functional unit by either obliteration or
      cranialization. The authors present a diagnostic and therapeutic algorithm for
      the operative management of frontal sinus fracture and discuss the complications
      that have been encountered in the authors' experience with frontal sinus
      fractures.

PMID- 11951449
TI  - Special considerations in pediatric cranial fixation: a technical overview.
AB  - Advances in plate fixation design have made possible traumatic and elective
      cranial reconstruction in pediatric patients. Plating systems must be selected
      properly, particularly in growing infants and children, in whom long-term
      computerized axial tomography (CAT) scanning and magnetic resonance imaging (MRI)
      may be necessary. Specific concerns include an actively growing skull with
      resulting dynamic bony contour changes. The results of 41 children with
      approximately 5 plates per case, totaling 205 implantable devices, were studied.
      This article addresses safety and image quality of metallic implants on CAT scan
      and MRI scanning, growth restriction induced by rigid plating systems, passive
      internal displacement of plates and screws with possible dural and cortical
      penetration, plate and screw isolation, and recommendations for cranial fixation
      in children.

PMID- 11951450
TI  - Eosinophilic granuloma masquerading as fracture of the orbital roof: case report.
AB  - Orbital involvement of eosinophilic granuloma accounts for less than 1% of all
      orbital tumors. The most common presenting sign of eosinophilic granuloma is
      bilateral or unilateral proptosis; rarely, neural parenchyma involvement is
      observed. This article features a case report of a 16-year-old male patient who
      presented to the authors after minor trauma that simulated a fracture near the
      orbital apex. The authors conclude that the diagnosis of eosinophilic granuloma
      should be considered if there is unusual location of apparent "fracture," a mass
      in the region of the fracture, lysis of bone, and recurrence of inflammation
      after the initial injury has subsided. Timely intervention with appropriate
      excision, histologic confirmation, and reconstruction with proper follow-up are
      the cornerstones of therapy for this rare disorder.

PMID- 11951451
TI  - Endoscopic repair of frontal sinus fracture: case report.
AB  - Although the benefits of endoscopic techniques including direct visualization as
      well as minimization of scars and morbidity have been employed in general,
      gynecological, and thoracic cases, only recently have plastic surgeons begun to
      champion endoscopic procedures in their practices. The authors describe an
      endoscopic procedure that reduces an anterior wall frontal sinus fracture through
      two 1.0 cm paramedian stab incisions located less than 1.0 cm behind the hairline
      of a 13-year-old female patient. The repair, performed in the bloodless
      subperiosteal plane, was executed with a 30 degrees endoscope and endoscopic
      instrumentation. The patient had restoration of her cosmetic deformity and no
      postoperative morbidity. To the authors' knowledge, this represents the first
      description of endoscopic repair of a traumatic frontal bone defect.

PMID- 11951452
TI  - Classification of orbital floor fractures.
AB  - A retrospective series of orbital, axial, and coronal computed tomography scans
      from 24 orbital floor fractures was studied to define the anatomic location of
      the fracture. Floor fractures without rim involvement, which are referred to
      clinically as blowout fractures, were located medial to the infraorbital nerve or
      extended on both sides of the nerve. Floor fractures with rim involvement were
      associated with zygomatico-orbital or Le Fort II or III fractures, and were
      located either lateral to or on both sides of the infraorbital nerve. No blowout
      fractures were confined to the lateral half of the orbital floor and no floor
      fractures with rim involvement were confined to the medial half of the orbital
      floor. The authors propose a classification system for describing orbital floor
      fractures based on their anatomic location relative to the infraorbital nerve.

PMID- 11951453
TI  - Use of hard palate grafts for treatment of postsurgical lower eyelid retraction:
      a technical overview.
AB  - Lower eyelid retraction occasionally occurs following the repair of fractures
      involving the orbital rims, orbital floor, or complex zygomatic maxillary complex
      fractures. The surgical repair of these scarred eyelids has been historically
      difficult. The authors have utilized the principle of releasing the scar tissue
      and attempting to reposition the eyelid in its normal anatomic position by
      employing a hard palate mucosal graft spacer to correct the eyelid malposition.
      In this article, the authors discuss the excellent success they have experienced
      utilizing hard palate autologous grafts as spacers performing revision of scarred
      contracted lower eyelid retractors and tightening of the lateral canthal tendon
      complex. Adherence to the principles delineated in the article can yield
      excellent functional and cosmetic results.

PMID- 11951454
TI  - Intraoperative airway management with pan-facial fractures: alternative
      approaches.
AB  - Nasoendotracheal intubation is contraindicated in patients with pan-facial
      fractures for securing the airway during reconstructive surgery. Oral intubation
      interferes with intermaxillary fixation during fracture reduction. In these
      situations, elective tracheostomy is often the airway of choice. However, with
      the use of rigid internal fixation, postoperative maxillomandibular fixation is
      unnecessary and traditional tracheostomy may be avoided, unless oral intubation
      is impossible or long-term airway control is necessary. This article presents
      Bullard laryngoscopy and submandibular intubation techniques as innovative
      alternative methods of airway management during surgery. These procedures are
      indicated in those patients with severe injuries who do not require long-term
      airway management postoperatively and did not require tracheostomy in the
      emergency room.

PMID- 11951455
TI  - Trauma to the temporal bone: diagnosis and management of complications.
AB  - The temporal bone contains important sensory and neural structures that may be
      damaged in patients who experience craniofacial trauma. The most serious
      complications of temporal bone trauma include facial nerve paralysis,
      cerebrospinal fluid leak, and hearing loss. Injury to the temporal bone often
      presents with subtle signs and symptoms, such as otorrhea, facial palsy, and
      hemotympanum. A high index of suspicion and a thorough knowledge of how to
      diagnose injury to the temporal bone are paramount in treating patients who
      present to the emergency room with craniofacial trauma. This article provides an
      overview of temporal bone trauma, outlines a methodical approach to the patient
      with temporal bone trauma, details four cases, and describes the treatment of
      complications.

PMID- 11951456
TI  - Dog bites of the face with tissue loss.
AB  - Children are most frequently the victims of dog bites; the face is often the
      favored target. Even in apparently extensive injuries, enough skin generally
      remains to allow a reasonably direct closure, which is the preferred treatment.
      Infrequently, when significant soft tissue loss occurs, more complex methods
      require the surgeon's ingenuity in order to restore function and cosmesis without
      risking widespread infection or disfigurement. This article discusses the use of
      local flaps, skin grafts, or regional flaps in the proper circumstances. These
      options must be chosen carefully following an appropriate hierarchy of
      priorities, in order to achieve wound closure, to simultaneously restore anatomic
      landmarks, and to lessen the need for subsequent surgical revisions and
      psychological trauma.

PMID- 11951457
TI  - Health care reform is having a disturbing impact on basic medical research.

PMID- 11951459
TI  - Management of eyelid dog bites.
AB  - Eyelid dog bites are common facial injuries that occur frequently in children and
      often involve the lacrimal canaliculi. Even though the incidence of infection
      following repair of these lacerations is low, prophylactic antibiotics should be
      administered to all patients. Good function and appearance of repaired eyelid dog
      bites is achieved with appropriate surgical management. This article presents 2
      cases and a retrospective review of 7 patients with eyelid dog bite injuries
      evaluated and treated between August 1989 and June 1994; 6 of 9 patients were
      children. The lacrimal drainage system was lacerated in 6 of 9 patients. All
      patients underwent surgical repair of their injuries and received antibiotics
      directed at common canine oral bacterial flora. The patients were followed for a
      minimum of 3 months postoperatively. There was only 1 case of facial wound
      infection. Good functional results were achieved in all patients.

PMID- 11951458
TI  - Avoiding secondary brain injury after severe head trauma: monitoring and
      management.
AB  - Research has demonstrated that much of the mortality and morbidity in severely
      head-injured patients is due to secondary injury. The development of techniques
      to monitor cerebral blood flow, arteriovenous difference of oxygen or saturation
      of jugular venous blood flow with oxygen, and cerebral metabolic rate of oxygen
      has led to recognition, treatment, and prevention of secondary insults. This
      article examines the theoretical basis for the utilization of these techniques to
      guide the treatment of severely injured patients. Special emphasis is given to
      the factors governing both cerebral blood flow and cerebral blood volume, and how
      these factors can be monitored and manipulated to strike an optimal balance
      between the two. This information can aid in determining when it is safe to
      operate on patients with non-life-threatening conditions.

PMID- 11951460
TI  - Zygomatico-orbital fractures: historical perspective and current surgical
      management.
AB  - This article presents a general historical review of zygomatico-orbital (ZO)
      fractures with application of contemporary surgical procedures. Two surgical
      cases are presented, in which the ZO fractures were approached via a
      transconjunctival incision with a lateral canthotomy. A two-point rigid internal
      fixation, combined with a porous high-density polyethylene orbital floor
      reconstruction, produced uniformly excellent cosmetic and functional results in a
      total of 42 patients with ZO fractures who were treated over a 2-year period.

PMID- 11951461
TI  - Rigid fixation of facial fractures in children.
AB  - This article presents a retrospective analysis of a selective use of rigid
      fixation among 62 children with facial fractures, treated at a Level I trauma
      center over a 5-year period (1986-1991). There were 21 mandible fractures, 11
      orbital fractures, 11 zygomaticomalar complex fractures, 7 nasal fractures, 5
      maxillary fractures, 3 pan-facial fractures, 2 nasal-orbital-ethmoidal complex
      fractures, and 2 frontal sinus fractures. Only 18 children had rigid fixation of
      their injuries. Complications of Le Fort upper facial fractures repaired with
      rigid fixation involved perioperative sinusitis; one case required oral
      antibiotics, the other ethmoidectomy and maxillary antrostomy. One child with a
      Le Fort fracture had delayed exposure of a zygomaticomalar buttress plate, which
      required surgical removal. Permanent enophthalmos occurred in two children with
      Le Fort fractures. The authors conclude that traditional conservative management
      is appropriate in most cases. However, in children aged 13 and older with
      mandible fractures and children with complex mid- and upper facial fractures, a
      judicious use of rigid fixation has advantages over the traditional techniques.

PMID- 11951462
TI  - Superior orbital fissure syndrome: current management concepts.
AB  - The superior orbital fissure syndrome is an uncommon complication of craniofacial
      fractures: middle-third facial fractures and lesions of the retrobulbar space.
      This article reviews the anatomy and etiology of the superior orbital fissure as
      it relates to pathophysiology and physical findings. Cases reported in the
      literature are reviewed, emphasizing diagnosis and established treatment options.
      Two cases are presented and their management discussed, including the use of pre-
      and postoperative steroids as an adjunct to standard fracture reduction and
      stabilization therapy.

PMID- 11951463
TI  - Management of traumatic cerebrospinal fluid fistula.
AB  - Cerebrospinal fluid fistulae present a common management problem for the surgeon
      managing craniofacial trauma. Controversies exist concerning various aspects of
      treatment. These controversial management issues include cerebrospinal fluid
      drainage, antibiotic prophylaxis, timing of surgical intervention, and techniques
      of repair. Although most cerebrospinal fluid fistulae cease spontaneously, some
      fistulae persist, resulting in the potential for life-threatening complications.
      A review of these issues is presented, together with a suggested management
      protocol.

PMID- 11951464
TI  - Pseudo-entrapment of extraocular muscles in patients with orbital fractures.
AB  - Diplopia is a prominent finding in patients who have suffered orbital fractures.
      If the patient's double vision or ocular motility restriction was caused by soft
      tissue entrapment into the fracture site, surgery is frequently performed in
      order to release this entrapment and restore normal eye movement. However, the
      presence of diplopia should not necessarily be an indication for surgery. Brief
      case reports are hereby presented to illustrate that the symptoms of diplopia and
      motility restriction are not always attributable to the presence of orbital
      fractures that require surgical repair. The purpose of this article is to
      describe other causes of abnormal ocular motility that are associated with
      orbital trauma but which are not caused by soft tissue entrapment.

PMID- 11951465
TI  - Repair of orbital floor fractures with absorbable gelatin film.
AB  - Many materials have been utilized for the repair of orbital floor fractures.
      Absorbable gelatin film is a bioabsorbable sheeting material that is manufactured
      from denatured collagen. This material is appropriate for the repair of smaller
      orbital floor defects (5 mm or less) and trapdoor-type fractures; it is used with
      larger defects as an interpositional graft material between the periorbital
      tissues and as an orbital floor reconstruction plate or mesh. Sixteen cases
      consisting of both types of defects were retrospectively examined clinically and
      radiographically. Satisfactory results were obtained in all of these cases,
      including no adverse ocular signs or implant rejection, good facial form, good
      function, and acceptable postoperative radiography results.

PMID- 11951466
TI  - Comprehensive management of nasoethmoid-orbital injuries.
AB  - Fractures of the nasoethmoid-orbital region present some of the more formidable
      challenges to the reconstructive surgeon in regard to aesthetic and functional
      restorations. As the severity of injury escalates, the surgical difficulties
      increase, making acceptable results of therapy difficult to achieve. Optimal
      management involves not only repair of the skeleton of the central midface, but
      also restoration of function and aesthetics of the orbits, frontal sinus,
      anterior cranial fossae, and the overlying soft tissue. Detailed physical
      examination and radiographic imaging are necessary to properly diagnose the
      extent of injuries. Various surgical techniques, such as interfragmentary wiring,
      microplate fixation and transnasal wiring, are utilized. This article reviews
      injuries of the nasoethmoid-orbital region, and describes the pertinent anatomy
      and classification of injuries. Currently accepted methods of evaluation and
      repair of specific injuries are outlined.

PMID- 11951467
TI  - Lateral force compared with frontal impact nasal fractures: need for reoperation.
AB  - Patient concern over the outcome of correction of nasal fractures is usually
      extremely high; often, a secondary procedure is necessary. Therefore, thorough
      consultation is mandatory. The clinical data of 50 patients who sustained nasal
      fractures was retrospectively reviewed to determine if there was any predictive
      value to classification of nasal fractures and the likelihood of a secondary
      surgical procedure. Using Stranc and Robertson's nasal fracture classification,
      41 of 50 patients were described as lateral force fractures and 9 of 50 were
      frontal impact fractures. Five of 50 patients underwent a secondary surgical
      procedure, 4 from the frontal impact and 1 from the lateral force fracture group.
      The number of patients reoperated on approximately equaled the number who were
      dissatisfied with the result of the initial procedure (5 versus 6). However,
      objective assessment by the primary surgeon revealed 21 patients with an anatomic
      or functional defect. Of these, 15 were lateral force fractures (15 of 41, or
      37%) and 6 were frontal impact fractures (6 of 9, or 67%). These results
      illustrate the difficulty in restoring preinjury nasal anatomy and function,
      especially in the more severe and complicated frontal impact types of nasal
      fracture. Using this information can aid in obtaining satisfactory informed
      patient consent.

PMID- 11951468
TI  - The subcranial approach to trauma of the anterior cranial base: preliminary
      report.
AB  - The subcranial approach to the cranio-orbito-frontal junction allows direct
      access to the central anterior cranial base for repair of fractures, dural tears,
      and cerebrospinal fluid fistulae. It provides good visualization without brain
      retraction and is suitable in primary or delayed traumatic cases. For extended
      visualization, a portion of the frontal sinus may be removed and repositioned at
      the end of the procedure. Because the brain is not retracted, morbidity is low.
      Potential and active cerebrospinal fluid fistulae can be successfully managed
      with the use of free fascial grafts and often do not require a pericranial flap.
      Contraindications include parenchymal brain injury or bleeding that may require a
      more standard frontal craniotomy for management. The purpose of this report is to
      highlight the use of the subcranial approach to repair cerebrospinal fluid
      fistulae in immediate and delayed traumatic cases.

PMID- 11951470
TI  - Classification of autogenous skull grafts in cranial reconstruction.
AB  - Although the literature provides a general description of various techniques of
      reconstruction of the cranium with autogenous bone grafts, no classification
      exists outlining the options in an orderly fashion. A classification of
      autogenous skull grafts in cranial reconstruction is hereby presented. These
      grafts include bone dust, shave, sliding, transpositional, full-thickness split,
      and vascularized pedicle. The uses of each graft and its advantages and
      disadvantages are discussed. The location of the defect, the size, and the
      thickness of the skull are variables that must be considered in utilizing these
      grafts. Often a combination of grafts is required to provide the best cranial
      contour. Understanding the characteristics of these types of grafts provides the
      surgeon with the versatility necessary in reconstructing cranial defects.

PMID- 11951471
TI  - Management of traumatic optic neuropathy.
AB  - Visual loss caused by trauma to the optic nerve is a well-recognized sequela to
      cranio-maxillofacial trauma. The authors reviewed their experience with 90
      patients with pure traumatic optic neuropathy and optic nerve trauma with
      concomitant maxillofacial injuries. All patients were treated with intravenous
      steroids. Those not improving underwent extracranial optic canal decompression.
      Patients with initial visual acuity of 20/100 or better all responded favorably
      with improvement in visual acuity or visual field to a course of intravenous
      megadose corticosteroids. Patients with initial vision of 20/200 or worse who
      failed to respond to corticosteroids may have improved visual function after
      undergoing extracranial optic canal decompression. Preoperative and postoperative
      computed tomography scans on 6 patients enhanced with intrathecal iopamidol
      indicate the site of optic nerve compression to be at the optic canal. This
      article discusses the diagnosis and the medical and surgical treatment of pure
      and complex optic nerve injuries.

PMID- 11951472
TI  - Treatment methods for fractures of the mandibular angle.
AB  - Fractures of the mandibular angle are plagued with the highest rate of
      complication of all mandibular fractures. Over the past 8 years, the following
      six accepted forms of treatment for these fractures were performed on an indigent
      inner-city population: closed reduction or intra-oral open reduction and nonrigid
      fixation; extraoral open reduction and internal fixation with an AO/ASIF
      reconstruction bone plate; and intraoral open reduction and internal fixation
      using either two 2.0 mm minidynamic compression plates, two 2.4 mm mandibular
      dynamic compression plates, two noncompression miniplates, or a single
      noncompression miniplate. This article reviews the results of those treatment
      modalities when used for the same patient population at one hospital. Results
      show that the use of either an extraoral open reduction and internal fixation
      with the AO/ASIF reconstruction plate or intraoral open reduction and internal
      fixation using a single miniplate was associated with the fewest complications.

PMID- 11951473
TI  - The traumatic saddle nose deformity: etiology and treatment.
AB  - The saddle nose resembles a saddle, i.e., with a concave, often flattened dorsum
      and an apparent cephalic rotation of the nasal tip. The concavity may be present
      in the osseous or cartilaginous dorsum, or both. The saddle nose deformity can be
      divided into congenital, postinfection, postsurgical, and traumatic types.
      Congenital saddle nose deformity is rare, often accompanying midfacial deficiency
      malformation syndromes. The advent of antimicrobial therapy has helped restrict
      the incidence of syphilitic or leprotic saddle nose to the nonindustrialized
      nations. Postsurgical saddle nose deformity occurs most often as a result of the
      overzealous septorhinoplasty. The most common type of saddle nose deformity may
      be traumatic. The authors use Kazanjian and Converse's characterization of the
      true saddle nose as one in which the bony and/or cartilaginous portions are
      depressed and the projection of the nose is generally preserved. This article
      describes the saddle nose deformity and its etiology and proposes a management
      technique with minimal complications.

PMID- 11951474
TI  - Priorities in the management of penetrating maxillofacial trauma in the pediatric
      patient.
AB  - Penetrating facial trauma is uncommon in children; a large series published by
      Cooper et al revealed that only 1% to 2% of the total population of infants and
      children admitted for trauma during their study period had a diagnosis of
      penetrating trauma to the head or neck. Little has been published specifically
      addressing these injuries in the pediatric population. The records of 20 patients
      treated for penetrating facial injuries at Kosair-Children's Hospital in
      Louisville, Kentucky from January 1991 through December 1994 were reviewed. The
      location, mechanism and extent of injury, as well as the diagnostic and
      management practices used in patient treatment, were collected. Categorizing the
      injuries relative to the involvement of one or more facial zones helped guide
      diagnostic studies and therapeutic intervention and predict associated injuries.
      This article evaluates the authors' method of management and any differences in
      management between pediatric and similarly injured adult patients.

PMID- 11951475
TI  - Resorbable bone fixation: its potential role in cranio-maxillofacial trauma.
AB  - The concept of biodegradable bone fixation devices, which provide sufficient
      rigidity to allow fracture healing and resorption thereafter, has significant
      appeal in cranio-maxillofacial trauma treatment; however, biodegradable bone
      fixation devices have not yet become available for clinical use in the
      craniofacial skeleton. This article reviews the obstacles in developing a
      resorbable polymer bone fixation system and describes the initial use of such a
      system in the treatment of cranio-maxillofacial trauma patients. It also
      discusses the potential role of a resorbable polymer bone fixation system in
      conjunction with the use of metal fixation in the management of facial fracture.

PMID- 11951476
TI  - Traumatic avulsion and reconstruction of the midface.
AB  - Traumatic loss of midface soft tissue and supporting structures may result in
      communication between the oral and nasal cavities. Reconstruction requires both
      oral and nasal lining, as well as supporting structures. The need for
      multilaminar tissue, as well as the paucity of local tissue, creates a
      reconstructive challenge. This case report describes the reconstruction of a
      traumatic defect of the alveolus, hard palate, inferior orbits, and local soft
      tissues. An intraoperative alginate mold facilitated a three-dimensional
      understanding of the wound, and allowed translation of an osseomyocutaneous groin
      flap to reconstruct the defect in one stage.

PMID- 11951477
TI  - Postconcussive symptoms in craniofacial trauma.
AB  - In a private/institutional setting the prevalence of Postconcussive Syndrome
      (PCS) symptoms and related etiologic factors was surveyed in 122 concussion and
      other craniofacial trauma patients (mean age 32 years; 68% male) and 122
      uninjured controls (mean age 21 years; 45% males). A Neurobehavioral Symptom
      Checklist was used to measure 44 self-related symptoms, summed to yield Overall
      Frequency; number of symptoms rated as 3 or 4 were also summed separately to
      yield High Frequency scores. The Concussion group had significantly greater
      Overall Frequency and High Frequency scores than the other patients and the
      controls. The Brain Damage group had significantly greater High Frequency (but
      not Overall Frequency) scores than the controls. The presence of litigation,
      unemployment, or middle-age yielded significantly greater Overall Frequency
      scores in the patients; these variables in the control group were not measured.
      The presence of craniofacial fractures had no effect. Results suggest PCS
      symptoms are greatest in concussion patients with the presence of litigation,
      unemployment or middle age, and are less affected by injury severity.

PMID- 11951478
TI  - Endovascular management of aneurysm and carotid-cavernous fistulae from gunshot
      wounds to the skull base and oropharynx.
AB  - The clinician must be aware of the potential for vascular injury that can result
      from gunshot wounds to the skull base and oropharynx. These lesions can be life
      threatening or can result in irreversible neurologic defects. The goal is early
      diagnosis and efficient appropriate treatment. Endovascular therapy has been
      proven to be of great benefit for the treatment of traumatic aneurysms and
      carotid-cavernous fistulae. Utilizing either a reconstructive or a deconstructive
      approach, the traumatic lesions can be treated without the morbidity inherent to
      surgery of the skull base or cavernous sinus. This article discusses the authors'
      experience with endovascular treatment, explaining in detail the reconstructive
      and deconstructive approaches and providing clinical examples of the treatment of
      pseudoaneurysms and carotid-cavernous fistulae.

PMID- 11951479
TI  - Correction of late enophthalmos with polyethylene implant.
AB  - High density porous polyethylene (HDPP) has been used extensively for
      craniofacial reconstructive procedures. The authors recently reviewed the records
      of 21 patients who had undergone correction of late (more than 6 months)
      posttraumatic enophthalmos utilizing HDPP implants to restore orbital integrity
      and volume. Follow-up after implant placement was 6 months to 54 months (mean 20
      months). Twenty of 21 patients demonstrated a clinically significant reduction in
      enophthalmos to within 2 mm of the opposite globe, as demonstrated by Hertel
      and/or Naugle exophthalmometry and by clinical observation. There were no cases
      of worsened visual acuity, lid position or ocular mobility, and no HDPP implant
      became infected or was extruded. The authors' experience supports the safety and
      efficacy of HDPP implants for correction of mild to moderate posttraumatic
      enophthalmos.

PMID- 11951480
TI  - The mandible fracture: a treatment protocol.
AB  - Treatment of the mandible fracture is basic to the treatment of maxillofacial
      trauma. Although there is universal agreement as to treatment goals and
      therapeutic principles, a plethora of currently accepted treatment modalities
      indicates a lack of consensus. This article reviews 435 mandible fractures in 268
      patients treated by the Oral and Maxillofacial Surgery Service of Kings County
      Hospital/State University of New York Health Science Center at Brooklyn during a
      3-year period from July 1, 1992 to June 30, 1995. Fifteen cases required
      reoperation or readmission for a complication rate of 3.4%. There was
      satisfactory bone healing in 99% of the cases. Based on these results, a mandible
      fracture protocol is proposed.

PMID- 11951481
TI  - Complications of rigid internal fixation for mandibular fractures.
AB  - The application of rigid internal fixation to maxillofacial trauma is among the
      truly great advances that have been made in the field. The use of rigid internal
      fixation techniques has resulted in many advantages for the patient.
      Unfortunately, complications have occurred with this technology that are often
      devastating in their consequences for treatment outcomes. This article addresses
      some of the problems that stem from the use/misuse of rigid fixation devices in
      the treatment of mandibular fractures. It presents the most common complications
      and their management, including malunion, fibrous union, infection/osteitis, and
      impalement of the tooth roots and/or inferior alveolar canal.

PMID- 11951483
TI  - Orbital volumetric analysis: clinical application in orbitozygomatic complex
      injuries.
AB  - Fifteen patients with unilateral orbitozygomatic complex fractures and five with
      bilateral injuries were analyzed with respect to the differences in orbital
      volume between the affected and the uninjured, or other, side. The study was
      conducted using the ALLEGRO Workstation and software package from ISG
      Technologies, which was capable of calculating volume partitions from either
      axial or coronal images. Patients without postoperative enophthalmos demonstrated
      a maximum volume difference of 3.8%; those with enophthalmos demonstrated
      differences of 4% or greater. The Critical Volume Difference at which
      enophthalmos becomes clinically apparent (whereby the orbital-corneal distance
      measured by Hertel exophthalmometry is greater than 3 mm on the affected side) is
      in the range of 4% to 5%. Volume analysis of the orbits by manipulation of the
      computed tomography data may allow a better understanding of changes in orbital
      configuration, which can result in better-directed primary and secondary
      reconstructions.

PMID- 11951482
TI  - The bicoronal flap approach in craniofacial trauma.
AB  - The utilization of the bicoronal scalp flap in craniofacial trauma has proved
      indispensable in the management of severe craniofacial injuries. It provides vast
      exposure of such critical structures as the cranium, frontal sinus, orbit and
      upper midface, compared with that for previous techniques of facial fracture
      reduction. Although the flap has great utility, severe complications, such as
      facial nerve injury, diplopia, telecanthus, and scalp necrosis, can occur. This
      article reviews the surgical anatomy, technique, and indications for the safe
      utilization of the bicoronal scalp flap approach in the management of
      craniofacial trauma.

PMID- 11951484
TI  - The health maintenance organization (HMO) system presents a formidable challenge
      to both physicians and patients.

PMID- 11951485
TI  - Clinical case presentation: orbital reconstruction after traumatic optic
      neuropathy.

PMID- 11951486
TI  - Fatal necrotizing fasciitis following a mandibular fracture.
AB  - Necrotizing fasciitis of the head and neck is an uncommon, insidious infection
      that usually occurs secondarily to odontogenic infections, although blunt and
      penetrating trauma can be another cause. Of 65 total reported cases of
      necrotizing fasciitis, 10 (15.4%) have been fatal. This article presents a case
      of a mandibular fracture in a severely immunocompromised elderly patient in whom
      delayed treatment proved fatal. The clinician must remain suspicious of any
      infection refractory to antibiotic therapy alone, since necrotizing fasciitis is
      a rapidly progressing condition with high morbidity and potential for mortality.
      Rapid diagnosis, surgical treatment, antibiotic therapy, medical management,
      nutritional support, and early detection and treatment of complications are
      critical elements in the management of necrotizing fasciitis.

PMID- 11951487
TI  - Traumatic facial nerve injuries: review of diagnosis and treatment.
AB  - Both blunt and penetrating craniofacial trauma may lead to severe facial nerve
      injury and sequelae of facial paralysis. Initial evaluation involves quantitation
      of motor deficits using a clinical grading system, such as the House-Brackmann
      scale. High resolution computed tomography is used for localization of nerve
      injury in suspected cases of temporal bone trauma. In the absence of gross
      radiographic abnormalities, electrophysiologic testing helps predict the
      likelihood of spontaneous recovery. In patients with deteriorating facial nerve
      injuries by electroneuronography, surgical exploration is the preferred
      management. Primary end-to-end neurorrhaphy is the preferred management for
      transection injuries, while facial nerve decompression may benefit other forms of
      high-grade nerve trauma. Secondary facial reanimation procedures, such as cranial
      nerve crossovers, dynamic muscle slings or various static procedures, are useful
      adjuncts when initial facial nerve repair is unsuccessful or impossible. A review
      of facial nerve trauma management and case illustrations are presented.

PMID- 11951488
TI  - Porous polyethylene implant for orbital wall reconstruction.
AB  - Short-term and intermediate-term results from clinical use of high-density porous
      polyethylene implants for reconstructive orbital surgery have been encouraging.
      This article presents an intermediate-term result from one institution with a
      comprehensive comparative analysis of other available alloplastic materials. A
      patient survey of 32 cases of orbital reconstruction using porous polyethylene
      sheet implants was performed, with a mean follow-up period of 32 months (range 15
      to 67). All cases were trauma-related injuries. The result was compared with that
      of published reports of other alloplastic materials with specific emphasis on
      complication rates. Complication rate following the use of porous polyethylene
      sheet implants was 6%. This finding was consistent with those of other reports on
      porous polyethylene sheet implants. A consistent, satisfactory surgical outcome
      and low complication rate were observed. In the authors' review, the porous
      polyethylene implants compared favorably in a comparative analysis of other
      alloplastic materials.

PMID- 11951489
TI  - Self-inflicted gunshot wounds of the lower half of the face: the evolution toward
      early reconstruction.
AB  - The self-inflicted gunshot wound of the lower half of the face traditionally has
      been treated by multistaged and prolonged reconstructive maneuvers that often
      left significant and uncorrectable secondary deformities. Modern cranio
      maxillofacial methods for reduction and rigid fixation of the facial skeleton,
      using immediate autogenous bone grafts when required, also has been efficacious
      for the acute management of these severe gunshot injuries. These methods can
      reduce the previously expected morbidity. Today's improved outcomes also are a
      consequence of the use of more reliable regional flaps and microsurgical
      techniques, which permit the early and simultaneous restoration of bone and soft
      tissue loss once all devitalized tissues have been adequately debrided.

PMID- 11951490
TI  - Carotid-cavernous sinus fistulae in craniofacial trauma: classification and
      treatment.
AB  - Carotid-cavernous sinus fistulae (CCF) represent pathological communications
      between the intracavernous internal carotid artery and the cavernous venous
      sinus. Although trauma is the most common cause of high flow carotid cavernous
      fistulae, they are relatively uncommon in patients sustaining craniofacial
      trauma. Nevertheless, CCF require early diagnosis and rapid and effective
      treatment in order to prevent severe and significant morbidity. Clinical
      presentation may include pulsatile proptosis, ocular and orbital erythema,
      chemosis, diplopia, headaches, and visual loss. Cerebral angiography is currently
      the definitive diagnostic study. Obliteration of the fistula by endovascular
      techniques is the current mainstay treatment, and direct surgery is reserved for
      cases that have failed endovascular therapy. This article reviews clinical
      features, pertinent anatomy, and therapeutic approaches to carotid-cavernous
      sinus fistulae.

PMID- 11951491
TI  - [Inhibition activity of spirulina platensis proteins photo-immobilization
      biomaterial on proliferation of cancer cells].
AB  - The bioactive protein-phycocyanin and all the proteins of Spirulina Platensis
      were isolated and purified. Photo-reactive proteins were synthesized by coupling
      the proteins with (N-(4-azidobenzoyloxy)succinimide) and were spread onto the 24
      well cell culture polystyrene plate. Then the coated surface was exposed to
      ultraviolet irradiation for chemical fixation of proteins via the conversion of
      the phenylazido group to the highly reactive phenyl-nitrene which spontaneously
      formed covalent bonds with neighboring hydrocarbons. On these proteins
      immobilized polystyrene plates, the liver cancer cells 7402 were cultured under
      the serum-free conditions, and the inhibition activity on proliferation of liver
      cancer cells was investigated and analyzed.

PMID- 11951492
TI  - [Experimental studies on procedures and properties of natural derived scaffold
      materials of tissue engineered bone].
AB  - To detect the properties of natural xenogeneic bone derived materials which were
      processed with different physical and chemical treatments, we made fully
      deproteinized bone(FDB), partially deproteinized bone (PDPB), partially
      decalcified bone(PDCB) from pig ribs. Their morphological features, constitute
      components and mechanical properties were examined by scanning electron
      microscopy, x-rays diffraction analysis, mechanical assay and so on. The results
      showed that FDB, PDPB and PDCB maintained natural network pore system. The ratios
      of calcium to phosphorus were 1.81, 1.74 and 1.50, and the protein contents were
      0.01% +/- 0.02%, 22.41% +/- 0.83% and 35.75% +/- 2.12% respectively. The sequence
      of their mechanic strength was PDCB > PDPB > FDB. These data indicate that FDB,
      PDPB and PDCB possess natural network pore system. Their organic and inorganic
      component ratios and contents are different, so their mechanic properties are not
      alike. Additionally, more investigations will be necessary to detect the
      biocompatibility of the three different scaffold materials of natural derived
      bone.

PMID- 11951493
TI  - [Study of XW630 in promoting estrogen receptor expression in ovariectomized
      rats].
AB  - We adopted firstly the dextran-coated charcoal(DCC) and SP methods to detect
      estrogen receptor (ER) expression of bone tissue in ovariectomized(OVX) rats. The
      results demonstrate that in OVX rats, XW630 can significantly promote ER
      expression in bone tissue and increase the ER content. XW630 is superior to
      estrone in effectiveness. The results also reveal that the ER expression in OVX
      rat bone tissue decreases with the lapse of time, indicating that the expression
      of ER depends on the existence of estrogen.

PMID- 11951495
TI  - [Compounding techniques of bioactive ceramic and polymer biomaterials].
AB  - Some techniques of compounding bioactive ceramics and polymer biomaterials with
      mechanical and biological properties and the clinical applications of the
      composites produced are presented.

PMID- 11951494
TI  - [Relation between coronary artery disease and polymorphism of angiotensin
      converting enzyme gene].
AB  - This study was aimed to determine the relationship between coronary artery
      disease(CAD) and insertion/deletion(I/D) polymorphism of the angiotensin
      coverting enzyme(ACE) gene. The ACE genotypes of 105 patients with CAD (50 of
      them were accompanied by essential hypertension (EH)) and 102 healthy people were
      detected by polymerase chain reaction. The results showed that in terms of ACE
      genotypes, no significant difference was noted between CAD group and control
      group, nor was it observed between CAD group and CAD accompanied by EH group, and
      nor was it seen between CAD/CAD accompanied by EH group and control group. These
      findings suggest that there is no relationship between the polymorphism of ACE
      gene and CAD (including those accompanied by EH).

PMID- 11951496
TI  - [Current researches in keratoprosthesis].
AB  - This paper introduced the evolution of keratoprosthesis (KPs) from the earliest
      devices to the newly developed types, pointed out their drawbacks and discussed
      the properties that an ideal keratoprosthesis or a tissue engineering
      keratoprosthesis must possess. Recent researches focused on the use of porous
      polymers as the skirt of core-skirt keratoprosthesis and tried to improve the
      material's biologicial intergration.

PMID- 11951498
TI  - [Novel scaffold materials for tissue engineering].
AB  - In this paper, the resorbable and degradable biomaterials often used in recent
      years are reviewed. These materials include natural and synthetical ones such as
      collagen, protein fiber, chitosan, polylactic acid (PLA), polyglycolic acid(PGA),
      polyanlydrides, etc.

PMID- 11951497
TI  - [The actuality and trend of biomaterial effectiveness and safety evaluation].
AB  - The evaluation of biomaterial effectiveness and safety is a key step before the
      biomaterial approaches to clinics. In recent years, lots of new biomaterials with
      different composition, shape, implant site and use have been coming out and in
      need of more special, sensitive and systematic evaluation methods. With the
      development of immunology, microdetective technique, inbred strain mammal and
      other connective branches, there are many chances for the consummation and
      integration of biomaterial evaluation system. The three-"R" principle (replace,
      refine, reduce), that is, developing in vitro experiments, using sensitive,
      special and advanced evaluation methods, improving and reducing the member of
      experimental animals, as well as the fundamental rule, that is, establishing an
      evaluation system covering three levels (molecule, cell and body) will guide the
      research of biomaterial evaluation to more promising development.

PMID- 11951499
TI  - [Materials and structure design of artificial dermis equivalent based on
      collagen].
AB  - The schematic structure model, materials selection and microstructure modulation
      are introduced for the design of artificial dermis equivalent. The artificial
      skin should also possess a bilayer structure that imitates then natural skin,
      i.e. the top layer functions as a temporary epidermis which is composed of
      polymer elastomer that is permeable for moisture but not for water, the bottom
      layer is the skin regeneration template employing collagen based sponge. In
      addition to collagen, polysaccharides like glycosaminoglycan is also used in the
      artificial dermis equivalent in order to simulate the natural extracellular
      matrix of skin and to modulate the degradation rate. The pore size and morphology
      of collagen porous membranes can be controlled by variation of the pH value,
      concentration and freezing temperature. Hence, the microstructure of the dermis
      equivalent can be optimized. The collagen based artificial dermis equivalent thus
      fabricated may be an option to skin graft in the clinical treatment of full skin
      injuries and ulcers.

PMID- 11951501
TI  - [Progress in studies of tissue-engineered heart valves].
AB  - Valve replacement represents the most common surgical therapy for valvular heart
      diseases. However, the long-term results of the valve protheses in clinical use
      are not satisfying. Recently, with the development of tissue engineering, more
      and more studies are focusing on creating ideal valve substitutes through seeding
      autologous cells on biodegradable scaffold. This article describes the definition
      of valvular tissue engineering, the choice of scaffold biomaterials, the methods
      of cell culture and seeding, and the evaluation of tissue-engineered heart
      valves. Furthermore, the problems which should be resolved in the future are also
      presented in the article.

PMID- 11951500
TI  - [The study of photochemical immobilization of urease on polyether sulfone film
      surface].
AB  - A new method of using photoactivable ester with azido group was described to
      immobilize urease on polyether sulfone(PES) film surface. The effects of
      photoactive enzyme concentration, temperature, pH, irradiation time on the
      activity of immobilized urease were investigated. Reused times and storage
      stability were also studied. The results showed that the surface concentration of
      urease immobilized on PES surface was about 0.33 mg/cm2. When the irradiation
      time was 5 minutes, the relative activity of immobilized urease was the highest
      and the activity increased with the increase of the concentration of photoactive
      urease solution. The optimum pH and temperature of immobilized urease were 7 and
      50 degrees C respectively. The relative activity of immobilized urease was stable
      (50%) after 12 times reused at 50 degrees C.

PMID- 11951502
TI  - [Bone marrow mesenchymal stem cells: progress in bone/cartilage defect repair].
AB  - Mesenchymal stem cells (MSC) are thought to be multi-potent cells that have the
      potential to differentiate into lineages of mesenchymal tissues, including bone,
      cartilage, tendon, fat, muscle, and marrow stroma during embryo morphogenesis. In
      recent years, cells that have the characteristics of mesenchymal stem cells were
      isolated from marrow aspirates of human and a few animals. It was found that
      these cells retain the characteristics of stem cells in vitro and could be
      induced to differentiate exclusively into the osteocytic, chondrocytic,
      myoblastic and adipocytic lineages. It was demonstrated that MSC could heal
      clinically significant bone and cartilage defects in animal models. The role of
      MSC in repairing tendon defect was also testified. In addition, for its multi
      potential to differentiate into lineages of mesenchymal tissues, MSC could be
      used as gene vehicle for gene therapy of trauma care.

PMID- 11951503
TI  - [Formation of porous biodegradable scaffolds for tissue engineering].
AB  - This newly-emerging field uses tissue-specific cells in a three-dimensional
      organization, provided by a scaffolding material, to return functionality of the
      organ. For these applications, the choice of scaffolding material is crucial to
      the success of the technique. In addition to the chemical properties of the
      material, physical properties such as surface area for cell attachment are
      essential. Various methods of creating pores in these materials to increase
      surface area are reviewed here. Scaffolds formed using the different techniques,
      which include fiber bonding, solvent casting/particulate leaching, gas foaming
      and phase separation, are compared on the basis of porosity, pore size, and
      promotion of tissue growth.

PMID- 11951504
TI  - [Application of tissue engineering in bioartificial renal tubule].
AB  - Tissue engineering is a discipline involving both materials science, engineering
      and life science. It has found successful application in Bioartificial renal
      tubule assist device RAD which is still under development. Experiments have
      proved that RAD can serve as renal tubule to perform its transport, metabolic and
      endocrine functions in patients with acute or chronic renal failure.

PMID- 11951505
TI  - [Studies on biomechanics of human foot: a review].
AB  - The plantar pressure and shear force measurement, the function and effect of
      joints, bones and ligaments of foot during running and walking, and the modeling
      and finite element analysis of human foot are three important aspects in
      biomechanical study of foot. They are also the basis of the study of
      rehabilitation. In this paper, studies on the three aspects are reviewed, and
      further promising developments are proposed.

PMID- 11951506
TI  - [Study of functional magnetic stimulation].
AB  - Functional magnetic stimulation (FMS) is a new technique for stimulation on
      excitable neuromuscular cell and provides extensive applications with many
      advantages, such as deep stimulation, less pain, non-invasive approach and easy
      to operate technique. In this paper, the new reports of FMS are introduced
      including the principle, stimulator, coils, results of experiments and our
      research on analgesic effect of FMS.

PMID- 11951507
TI  - [Temporal-spatial analysis of evoked potentials].
AB  - Evoked potentials are widely used in clinical neurophysiology. The conventional
      analysis methods of evoked potentials are based on the waves in time domain.
      Analysis based on time-spatial domain will provide more information than simple
      time domain analysis. The existing temporal-spatial analysis methods, such as
      microstate, frequency domain analysis and event-related coherence, are introduced
      in this paper.

PMID- 11951508
TI  - [The studies and progress of MEMS-based micro surgical tools].
AB  - The MEMS-based micro surgical tools are a kind of new devices applied in the
      minimally-invasive surgery. This paper introduces their application background
      and basic technology first, and then lays emphasis on the typical research
      accomplishments in the world. Finally, the research activities in China and some
      of the difficulties about the work are discussed.

PMID- 11951509
TI  - [An alternative method of strain analysis on arterial walls].
AB  - As is well known, the zero stress state of an artery is brought by cutting a ring
      of the artery radically and then the ring segment springs open into a sector. The
      zero stress state is a foundation of strain analysis of an artery. There are two
      methods to measure the dimensions of a blood vessel in the zero stress state.
      First, it is a way to measure immediately an opening angle. Second, it is a
      method of assuming that a cut-open, stress-free specimen forms a circular sector
      and there are two edge angles. In this paper, we proposed a new method to measure
      the dimensions of an arterial wall in the zero stress state. The new method is to
      measure immediately the curve length of an arterial wall in zero stress state by
      computer image process (CIP). We used the curve lengths to define a standard
      circle for the strain analysis. We compared these three methods on descending
      thoracic aortas, common carotid arteries, and femoral arteries of white rabbits.
      Conclusions are: (1) the new method, that is the strain analysis method from the
      curve length, is the best method among the three methods of strain analysis; (2)
      the lengths of a ring segment (the length between D/2 and 2D) do not affect the
      dimensions of the zero stress state.

PMID- 11951510
TI  - [Study on blood compatibility of polyurethanes for catheters].
AB  - In this article, the blood compatibility of polyurethanes (PUs) made by ourselves
      for catheters is studied by hemolysis test, platelets adhesion test, kinetic
      thrombus time test and dynamic clot formation. The results showed that these PUs
      all have excellent blood compatibility. Among these PUs, H50-100 and H60-100 have
      best blood compatibility. Additionally, the relationship between the structure
      and blood compatibility is discussed.

PMID- 11951511
TI  - [Experimental study on an auditory method for analyzing DNA segments].
AB  - To explore a new method for analyzing biological molecules that have already been
      sequenced, an experimental study on an auditory method was carried out. The
      auditory method for analyzing biological molecules includes audible
      representation of sequence data. Audible representation of sequence data was
      implemented by using a multimedia computer. Each mononucleotide in a DNA sequence
      was matched with a corresponding sound, i.e., a DNA sequence was "dubbed" in a
      sound sequence. When the sound sequence is played, a special cadence can be
      heard. In the audible representation experiment, special cadences of different
      exons can be clearly heard. The results show that audible representation of DNA
      sequence data can be implemented by using a multimedia technique. After a 5-time
      auditory training, subjects both in internal testing and external testing can
      obtain 93%-100% of judgment accuracy rate for the difference between two sound
      sequences of two different exons, thus providing an experimental basis for the
      practicability of this method. Auditory method for analyzing DNA segments might
      be beneficial for the research in comparative genomics and functional genomics.
      This new technology must be robust and be carefully evaluated and improved in a
      high-throughput environment before its implementation in an application setting.

PMID- 11951512
TI  - [Study of a new microwave applicator for hyperthermia treatment of uterocervical
      cancer].
AB  - A new microwave applicator for intracavitary hyperthermia treatment of
      uterocervical cancer has been designed and tested. Compared with the traditional
      microwave applicators, the exposed inner conductor of this applicator is replaced
      by a cone-helical antenna with the reflect shade. We confirm that the heat
      pattern of the applicator is shifted towards the tip in muscle tissue equivalent
      phantom material. The result indicates that this new applicator may play an
      important role in clinical use for treatment.

PMID- 11951513
TI  - [Study of noninvasive measurement of venous pressure].
AB  - A new device that allows noninvasive measurement of venous pressure has been
      invented in our laboratory and tested for its feasibility and validity. The
      device consists of four parts: 1. the air infusion system; 2. the pressure sensor
      gauge; 3. signal transducer and data processing system 4. the fixing apparatus.
      The correlation between noninvasive pressure and invasive pressure has been
      studied in vitro test on a saphenous vein model and in vitro test on dog's portal
      venous system. In vitro and vivo study, an excellent correlation between
      noninvasive pressure and invasive pressure was obtained(r = 0.99, P < 0.0005; r =
      0.97, P < 0.005). These data suggest that the new device allows a noninvasive
      measurement of venous pressure especially for the large veins such as vena cava,
      venae pulmonales and esophageal varices.

PMID- 11951514
TI  - [A tissue-engineered strain scaffold for three-dimensional cell cultures].
AB  - This article introduces a three-dimensional scaffold which is used to perform
      three-dimensional cell culture under mechanical stretch from the point of
      construction of tissue-engineered tissue. The composition, structure, surface
      characteristics, mechanical property, and cell compatibility of the scaffold have
      been studied by using surface chemistry and material mechanics testing methods.
      The results indicate that the polyvinyl alcohol (PVA) sponge, which is water
      tolerant, coated with Poly-DL-lactic-co-glycolic acid (PLGA) possesses a good
      nature in appropriate surface feature, porosity, elastic recoil, and cell
      compatibility. These features provide wide options for using this scaffold to
      study the effects of mechanical stretch on cells maintained in three-dimensional
      culture to provide a three-dimensional matrix.

PMID- 11951515
TI  - [Study on chitosan and PHBHHx used as nerve regeneration conduit material].
AB  - Both Chitosan and PHBHHx are natural, biodegradable biomedical materials. In this
      article, their ability to be made as nerve regeneration conduits are evaluated by
      studying their wettability, changes of the second structure of protein absorbed
      on their surface, growing status of fetal rat cerebral cortex nerve cells
      cultured on them, mechanical properties and ability to be processed later. The
      results indicate that both Chitosan and PHBHHx are promising nerve conduit
      materials.

PMID- 11951516
TI  - [Study of encapsulation of suicide gene in poly(D,L-lactic-co-glycolic acid)
      nanoparticles and its characteristics in vitro].
AB  - We constructed the AFP promotor, suicide gene and EGFP eukaryotic expression
      vector recombinant plasmid, and this plasmid DNA was encapsulated by
      biodegradable, biocompatible polymer PLGA to prepare nanoparticles. The results
      demonstrate that the mean diameter of DNA-PLGA-NP is 68 nm, the encapsulation
      ratio reaches to 80%, and the PLGA nanoparticles can protect plasmid DNA from
      digestion by deoxyribonuclease I (DNaseI) and sonication-induced shearing in
      vitro.

PMID- 11951517
TI  - [Analyses of the results of an animal experiment on graft-heparin conduits].
AB  - We inserted the 0.6 mm caliber graft-heparin (in inner wall) conduits into the
      tailarteries of 14 mice. The results showed that the graft conduit could be used
      repeatedly with no blood oozing out in the wound, no massive internal hemorrhage,
      and no additional coagulative reagent given during the whole experiment. On the
      other hand, the graft-heparin conduits of variant caliber were inserted into the
      femur arteries of 4 rabbits and 4 dogs for blood pressure experiment and femur
      arterio-venous bypass tests. The results showed that the anticoagulative effect
      of these conduits was markedly improved, but there was a strip of thrombus. There
      was no thrombus track in the wall of the conduit. The strip of thrombus was
      formed first in the cone of conduit where caliber changed. The results indicate
      that the blood flow resistance is in inverse proportion to 4 power of the conduit
      radius. So the thinner the conduit is, the more sensitive to conduit radius
      variation the conduit resistance will be. In studying and making the arfificial
      conduit, one must take notice of the conduit caliber, which should be equal to
      the caliber of the blood vessel.

PMID- 11951518
TI  - [Investigation on culture of rat pulmonary microvascular endothelial cells and
      their viscoelasticity].
AB  - It is the infent of this study to establish a simple method for cultivation of
      rat pulmonary microvascular endothelial cells(PMVECs) and investigate the
      viscoelasticity of PMVECs. First, we obtained rat's peripheral pulmonary tissue,
      which then was cut into small pieces and cultured with 3 ml DMEM containing 20%
      bovine calf serum, 90 U/ml heparin, 4 mmol L-glutamine, 100 U/ml penicillin and
      100 micrograms/ml streptomycin. Next, moved away the pulmonary tissue pieces 60 h
      later, and started passage 2-4 days after continued culture. Last, digested and
      separated PMVECs and studied viscoelastic coefficients of PMVECs by using
      micropipette aspiration technique. The results revealed that the cultured PMVECs
      showed regular cobblestone morphology and conformed with endothelial cells
      morphological characterization by phase contrast microscopy. PMVECs elastic
      modulus K1 was 49.3 +/- 9.2 Pa, K2 was 73.2 +/- 24.8 Pa, and it's viscosity
      factor mu was 19.2 +/- 7.2 Pa. s. These data demonstrate that it is feasible to
      cultivate PMVECs with tissue pieces method, and PMVECs is of greater rigidity.

PMID- 11951519
TI  - [Quantitative characterization of adsorbed bovine serum albumin on modified
      surfaces of poly(ether urethane) materials using ATR-FT-IR spectroscopy].
AB  - Attenuated total reflection (ATR) FT-IR spectroscopy was used to quantitatively
      characterize the extent of bovine serum albumin (BSA) adsorbed on the surface
      coating-modified poly(ether urethane) (PEU) matrix. The two surface modifying
      additives (SMA) were respectively a tri-block-coupling-polymer of stearyl poly
      (ethylene oxide)-4,4'-methylene diphenyl diisocyanate-stearyl poly(ethylene
      oxide), for short MSPEO, and another similar block-coupling polymer with the
      Cibacron Blue F3G-A endgroups, for short cibaMPEO. The experiments of static BSA
      adsorption were composed by two parts. One was static isothermal adsorption, and
      the other was static adsorption kinetics. The quantitative characterization was
      based on the optical principles of FT-IR, method of experiment and index of the
      apparatus, by which the enhancement of BSA adsorption on the SMA-modified
      surfaces was confirmed.

PMID- 11951520
TI  - [Time-dependent effects of interleukin-8 gene expression in endothelial cells
      exposed on fluid shear stress].
AB  - Fluid shear stress plays an important role in vascular biology. In vivo,
      endothelial cells are continuously exposed to mechanical shear stress generated
      by the flowing blood. Previous studies have identified the exposure of vascular
      endothelial cells to fluid mechanical forces can modulate the expression of many
      genes involved in vascular physiology and pathophysiology. To investigate the
      role of fluid shear stress on IL-8 expression in human umbilical vein endothelial
      cells (HUVECs), we employed quantitative reversal transcription-polymerase chain
      reaction (qRT-PCR) to assay the expression of IL-8 mRNA. Here we show that IL-8
      mRNA did not express in HUVECs untreated with fluid shear stress. IL-8 mRNA
      expression increased when HUVECs exposed to fluid shear stress for 1 h, and it
      reached the summit when HUVECs exposed to fluid shear stress for 2 h. Then IL-8
      expression gradually decreased at 3 h of stimulation by shear stress and remained
      at a constant level throughout the time course of the study. The increase of IL-8
      expression by shear stress was time-dependent. The biphasic response of IL-8 gene
      expression was found in experiments in which the applied shear stress was 2.23
      dyne/cm2, 4.20 dyne/cm2, or 6.08 dyne/cm2. IL-8 gene expression in response to
      shear stress was very similar to NF-kappa B in response to shear stress. The
      induction of IL-8 gene expression by fluid shear stress is probably due to the
      activation of NF-kappa B. This in vitro study demonstrates the expression of IL-8
      gene can be regulated by shear stress. Fluid shear stress induces a biphasic
      response of human IL-8 gene expression in HUVECs. These considerations suggest
      that IL-8 expression induced by fluid shear stress in HUVECs may play an
      important role in the genesis and development of both inflammation and
      arterioatherosclerosis.

PMID- 11951521
TI  - [Changes in extracellular matrix of endothelial cells co-cultured with VSMC under
      shear stress].
AB  - The construction and amount of fibronectin (Fn), laminin (Ln) and collagen type
      IV (ColIV) in the extracellular matrix of endothelial cells (EC) co-cultured with
      vascular smooth muscle cells (VSMC) under shear stress were studied by immuno
      fluoro-cytochemistry, laser confocal scanning microscopy and image analysis
      methods to detect the effect of shear stress on adhesion of EC for vascular
      tissue engineering. One group of EC was maintained under static conditions as a
      control. In the control, both Fn and Ln exhibited as a granular pattern in
      perinuclear area and a fibrillar pattern localized underneath EC, and Col IV
      exhibited mainly as the granular in the perinuclear area, but the fibrillar was
      fewer. On exposure of EC to shear stress in physiological range, Fn grouped into
      fibril tracts, and there was a tendency for some of these tracts of fibrils to
      align with direction of shear stress. Ln and Col IV also grouped into fibril
      tracts, which, in contrast to Fn, were randomly oriented, Simultaneously, all
      contents of the extracellular matrix had different quantitative alterations.
      These results suggest that the capability of adhesion of EC co-cultured with VSMC
      may be strengthened under shear stress.

PMID- 11951522
TI  - [The changes of cardiovascular response to orthostatic stress caused by
      hypovolemia induced by weightlessness: a simulation study].
AB  - We introduced the method of computer simulation in the studies of gravitational
      physiology. Based on work of Melchior (1994), we developed a mathematical model
      that can be used to stimulate cardiovascular responses to orthostatic stress
      (lower body negative pressure, LBNP). The model includes 7 sub-models: the
      redistribution of blood, the filling of left ventricle, left ventricle working,
      peripheral circulation, control of heart rate (HR), control of peripheral
      resistance and control of venous tone. Then we simulated the changes of blood
      pressure (BP) and heart rate during lower body negative pressure, and the results
      agreed well with the results of our human experiment. By using the developed
      model, we also simulated the effects of hypovolemia on the BP, HR and shock index
      during orthostatic stress. The simulation results indicate that the
      cardiovascular responses to orthostatic stress change significantly when the
      decrease of blood volume is more than 15% of the total blood volume. However, if
      the amount of the decrease of blood volume is less than 5% of the total blood
      volume, HR and BP could be maintained in normal range by the regulation of
      baroreflex during LBNP. Our simulation results suggest that hypovolemia may be
      the main cause of orthostatic intolerance induced by weightlessness.

PMID- 11951523
TI  - [A hemodynamics model describing cardiac deficiency of qi(vital energy)].
AB  - Cardiac deficiency of qi(vital energy) is one of the main syndromes in terms of
      TCM (Traditional Chinese Medicine). Based on our analysis of blood-tissue fluid
      circulation, we set up a hemodynamics model describing cardiac deficiency of qi.
      The model's theoretical results can reflect the manifestations of cardiac
      deficiency of qi, and are identical to those of clinical experimental
      discoveries, therefore it has substantiated our theory-cell's abnormal
      physiological function caused by undernourishment of tissue fluid is the reason
      of qi-deficiency.

PMID- 11951524
TI  - [The convection and diffusion of oxygen and carbon dioxide in the human airway].
AB  - The convective-diffusive problems of oxygen and carbon dioxide in human airway at
      normal respiratory status were studied theoretically in the present paper. The
      human airway was idealized as a bifurcated(two-branch) trachea tree, based on the
      understanding of the physiological structure of the human airway, and on
      Horsfield-Wanner optimization analysis about the trachea system status. It was
      assumed that the gases in the airway were incompressible, viscous fluid, due
      mainly to the characteristics of the low pressure drop and low rate of the gases
      within the human airway. One dimensional, non-steady convective-diffusive
      equations of oxygen and carbon dioxide were solved using Lax-Wendroff finite
      difference method, i.e., the so called three-legged finite difference method. The
      boundary conditions were set up according to the two different situations,
      respectively. The computational results showed the reasonable distributions of
      the concentration of oxygen and carbon dioxide in the human airway, respectively.

PMID- 11951525
TI  - [Three-dimensional finite element analysis on cell culture membrane under
      mechanical load].
AB  - A three-dimensional finite element model of the cell culture membrane was
      developed in the culture device under tension state made by us. The magnitude of
      tension and the displacement distribution in the membrane made of silicon rubber
      under different hydrostatic load were obtained by use of FEM analysis. A
      comparative study was made between the numerical and the experimental results.
      These results can serve as guides to the related cellular mechanical research.

PMID- 11951526
TI  - [A method based on independent component analysis for processing fMRI data].
AB  - Independent component analysis (ICA) is a new technique in statistical signal
      processing to extract independent components from multidimensional measurements
      of mixed signals. In this paper, for the processing of functional magnetic
      resonance imaging(fMRI) data, two signals of near voxels are used as the mixed
      signals and are separated by ICA. The correlation coefficients between the
      reference signal and the separated signals are calculated and those voxels whose
      correlation coefficients are greater than a threshold are considered to be the
      activated voxels by the stimulation, and so the functional localization of the
      stimulation is completed. The validity of the method was primarily proved by
      trial of real brain functional magnetic resonance imaging data.

PMID- 11951527
TI  - [Research on HRV signals for heroin addicts].
AB  - In this paper, the method of power spectral estimation is used to analyze the
      heart rate variability (HRV) signals for 15 heroin addicts and 15 healthy
      persons. The analysis result shows that there is a significant difference of the
      locations of the high-frequency peaks between the power spectra of heroin
      addicts' HRV signals. It means that the locations for heroin addicts lie in 0.437
      +/- 0.064 Hz and the locations for healthy persons lie in 0.325 +/- 0.052 Hz.

PMID- 11951528
TI  - [A methodological study of measuring quantitatively turbulent shear stree
      downstream of mitral stenosis in vivo using Doppler echocardiography].
AB  - In order to establish a method for measuring quantitatively turbulent shear
      stress (TSS) downstream of mitral stenosis in vivo based on Doppler
      echocardiography and computer-aided image analysis, we used doppler
      echocardiography to record the spectrum of flow velocity downstream of mitral
      valve at several locations in normal persons and in patients with mitral
      stenosis. With the computer-aided analysis of spectrum images, the magnitude of
      TSS was measured at the locations. The results demonstrate that no matter how
      severe the mitral stenosis is, the TSS and relative turbulent intensity(Irel) at
      the central locations of jet are lower than those at the marginal ones. A
      significant difference in the quantitative items of TSS, Irel and flow field
      uniformity between normal persons and patients with varying-degree of mitral
      stenosis was noticed (P < 0.05). There was a significant correlation between
      these items and effective orifice area (EOA), and we found that the smaller EOA
      is, the more severe the extent of stenosis is and the greater the magnitude of
      both TSS and Irel are, and that the highest magnitude of TSS is focused on the
      marginal area of jet. These results indicate that there is an obvious correlation
      between TSS(measured by Doppler echocardiography combined with computer-aided
      image analysis) and flow field uniformity. They can coincidently reveal the
      hemodynamic changes resulting from mitral stenosis of varied severeness, implying
      that our method could exactly depict the magnitude of TSS downstream of mitral
      stenosis in vivo and is non-invasive and good for anti-disturbance. The method
      can be used to analyze quantitatively TSS in the flow field of heart valve in
      patients with valvular diseases.

PMID- 11951529
TI  - [Measuring human arm motion parameters based on high-speed camera].
AB  - A sensing method based on high-speed camera is proposed to recognize human arm
      motion in this paper. A sensing system for human arm motion was established. A
      fast image processing algorithm was developed to accurately extract marker
      positions in the image. Angle parameter results were further improved with the
      instantaneous joint center principle. The human motion information results can
      serve as the research references of medical treatment, gym, bionics, and so on.
      The sensing method can also be applied to other fields of the human motion
      recognition.

PMID- 11951530
TI  - [Study on the complete conditions for exact reconstruction in volume CT].
AB  - Computed Tomography(CT) is one of the successful methods, in which mathematical
      theories are combined with engineering technology. Volume CT will replace the
      cross-sectional CT that has been widely used. In this paper two new cone vertex
      orbits, which are circle-and-arc and regular triangular pyramid lines, have been
      proposed and their complete conditions for exact reconstruction have been
      obtained. After having studied circle-and-n-line cone vertex orbit which is one
      of the important orbits in volume CT, we have given a better proof about the
      complete condition in circle-and-line and circle-and-2-line cone vertex orbit and
      have obtained some proper conclusions. Finally, we extend the above results to
      circle-and-n-line vertex orbit. These results will be useful for the design of
      direct volume imaging.

PMID- 11951531
TI  - [Measurement and classification of geometric parameters in Chinese proximal
      femur].
AB  - This study sought to establish a set of hip prostheses for the Chinese population
      and improve the design guidelines for hip prostheses. 480 cadaveric adult femora
      were obtained for X-ray imaging. 21 geometric parameters of femora were sampled
      on the anteroposterior(AP) and mediolateral(ML) views of radiograph in
      conjunction with computer-aided image processing technology. The curves of canal
      of proximal femur were fitted and made statistics. Pattern recognition was used
      to classify these geometric parameters. The results of classification
      corresponded with the 10 groups of data for design. On the basis of the numerous
      set of data, the results and classification would serve as means and guidelines
      for optimizing the design of prosthetic components and so far as custom-built hip
      prosthetics.

PMID- 11951532
TI  - [Simulation study of Kubicek formula for cardiac stroke volume calculation by 3
      dimensional finite element method].
AB  - This paper deals with the clinical application value of Kubicek formula for
      cardiac stroke volume calculation from the angle of Kubicek model simulation by 3
      dimensional finite element method. In the process of computer simulation, we have
      made a comparison between the result of model simulation, the specific value of
      Kubicek formula for cardiac stroke volume calculation, and the theoretical value
      of the prescribed model. The simulation results showed that an approximately
      linear relationship exists between the impedance change and the blood volume
      change of the aorta in the model, which has proved that Kubicek formula for
      cardiac stroke volume calculation has great clinical application value. On the
      other hand, the new method has opened up a path for studying the basic theory of
      impedance cardiography.

PMID- 11951533
TI  - [Basis of art phonetics in biomedical engineering].
AB  - Art phonetics' medicine, a new branch of traditional medicine, has not been
      developed perfectly, especially in the aspects of objective and scientific study.
      In this paper, the acoustical and anatiomical basis of art phonetics in viewpoint
      of biomedical engineering is explored, and then our work of quantitative
      measurement and analysis of art phonetic is introduced. The experiment data show
      further that quantitative measurement and analysis plays an important role in art
      phonetic medicine.

PMID- 11951534
TI  - [Location of the probe dots in gene chip image with the medialness function].
AB  - For acquisition of the gene chip information, how to correctly locate the probe
      dots in the chip's scanning image is the base of the chip information processing.
      Here we present a new approach for locating the probe dots in the gene chip
      image. First, a medialness function, which is good at detection of circle area
      with radius given in advance, is used for calculating the medialness map in which
      the center of circle sample area of the gene chip image is disclosed prominently.
      Then, a method to locate the probe dots center is given based on the medialness
      map and the 2D space configuration of the probe dots. The experiments show that
      the new approach correctly locates the probe dots while against noise affection
      robustly.

PMID- 11951535
TI  - "So you've just been hired into your first supervisory position..." (a temporal
      voice from the trenches).

PMID- 11951536
TI  - Recruitment and retention topics for a changing environment in medical imaging.

PMID- 11951537
TI  - Keeping employees in place: your place.

PMID- 11951538
TI  - As we see it. Who are you going to call?: Laboratorians share struggles,
      solutions when reporting critical values.

PMID- 11951539
TI  - Communications at the 95% confidence level: the impossible dream?

PMID- 11951541
TI  - On mentoring.
AB  - Mentored individuals develop into more broadly skilled employees than do those
      without mentoring. Mentors, proteges, and organizations benefit. As the average
      working laboratorian population ages toward retirement, organizations may wish to
      develop mentoring programs to help retain unwritten operations knowledge in the
      workplace.

PMID- 11951540
TI  - Lowering bad debt in health care: the cure is easier than you think.
AB  - In the year 2000 alone, according to one estimate, the health-care industry wrote
      off more than $20 billion in bad debt. Often, lack of patient payment is because
      the bill never reached the patient. In our mobile society, a current address is
      harder to find. Compound this with the fact that laboratories often receive
      information from clinics and hospitals that is incorrect or incomplete, and one
      begins to see the problem. Through learning about Internet-based search tools,
      health-care workers will recognize that incorrect billing information--the source
      of many unpaid bills--easily is corrected inexpensively, at a fraction of the
      cost of previous solutions.

PMID- 11951542
TI  - Utility scores for dimensions of clinical laboratory testing services from two
      purchaser perspectives.
AB  - Information is critical for making health-care purchasing decisions. Identifying
      the importance of dimensions and criteria used by purchasers of clinical
      laboratory testing services is the second step in the development of a report
      card to evaluate such services. The purpose of this study was to quantify the
      utility--the importance of four dimensions: access, cost, quality, and service-
      for two stakeholders of clinical laboratory testing services. Data were collected
      using a survey of hospital laboratories, as well as independent practice
      associations (IPAs) and preferred provider organizations (PPOs) that purchase
      clinical laboratory testing services. Although valued differently with respect to
      the magnitude of the utility score, both stakeholders rate quality and cost as
      first and second in importance. Managed-care organizations rate access and
      service as third and fourth in importance. Hospital laboratories consider service
      third in importance, yet with a similar utility score as that for managed-care
      organizations. Ten of 19 criteria (52.6%) were rated differently by the
      stakeholders. Using these utility scores for the dimensions and the criteria
      serves as a preliminary scoring system for a report card to evaluate clinical
      laboratory testing services.

PMID- 11951543
TI  - Stand and deliver: the art of speaking in public.
AB  - Anyone who took Latin in high school learned that many English words are derived
      from Latin roots. One such word is auditorium. It comes from the Latin words
      audio, which means "to hear," and taurus, which means "the bull." Therefore, an
      auditorium is a place where people go to hear the bull. This article is written
      to change that. It is written to end the bull. Carmen Mariano has spoken before
      audiences in seven states and five countries. He has a master's degree from
      Harvard University and a doctorate from Boston College. Neither degree has cured
      Carmen of his Boston accent, but both have taught him something about the power
      of the spoken word. Carmen shares that knowledge, and that power, in this
      article. And that is no bull.

PMID- 11951544
TI  - Instilling a soul in your organization without losing yours to it.
AB  - Health-care professionals are accustomed to struggling with ethical
      considerations brought about by advances in the medical sciences. How aware are
      these professionals of the ethical dilemmas created by advances in the management
      sciences? Deeply embedded in organizational and departmental changes are
      theories, paradigms, and philosophies that often are understood poorly even by
      their promoters. Although these system changes can occur at glacial speed, they
      also can be glacial in their effects on an organization's culture. Are
      individuals aware that the latest implemented management fad is changing their
      behaviors? By becoming mindful of the potential ramifications of change,
      individuals increase their ability to behave in a civil manner--that is,
      ethically choosing to embrace or resist the change. By acting within their own
      sphere of influence, civil individuals at all levels of the organization
      collectively instill a soul in their organization rather than losing their own
      souls to it. This article is adapted from a commencement speech presented to
      graduates of an executive health-care administration program. Most of these
      graduates were a mixture of hospital department heads, middle managers, and a few
      medical and hospital executives. Each year, I distribute my current version of
      this teaching note or mini-lecture to students completing my leadership class in
      hope that it will help them put in perspective the appropriate use of the
      management sciences they intensely study.

PMID- 11951545
TI  - Career development strategies. Management of self: Part Two.

PMID- 11951546
TI  - Case studies in ethics. Manager in the middle.

PMID- 11951547
TI  - Dollar$ & $en$e. Common cent$ 5: death and taxes.

PMID- 11951548
TI  - Best practices in customer service. Report cards.

PMID- 11951550
TI  - [Education in two worlds?].

PMID- 11951549
TI  - [From career pathway guide to career pathway counseling].

PMID- 11951551
TI  - [Moments for reflection are important].

PMID- 11951552
TI  - [A problematic case].

PMID- 11951553
TI  - [Ethical decision making in interdisciplinary intensive care].

PMID- 11951554
TI  - [Why fly with the time?].

PMID- 11951555
TI  - [The time that stays...].

PMID- 11951556
TI  - [What manner of care will you choose?].

PMID- 11951557
TI  - [A necessary and welcome patient care team].

PMID- 11951558
TI  - [Learning with motivation instead of frustration].

PMID- 11951559
TI  - [Not a spoken regulation, but an open door].

PMID- 11951560
TI  - [A new practice in anesthesia-resuscitation].

PMID- 11951561
TI  - [The work environment as a learning environment].

PMID- 11951565
TI  - [Osteosynthesis of trochanteric fractures using proximal femoral nails].
AB  - PURPOSE OF THE STUDY: Presentation of the existing experience in the use of
      Proximal Femoral Nail Synthes (PFN) in trochanteric fractures. MATERIAL: A
      prospective study evaluating a group of 41 patients, 12 men and 29 women, average
      age 68 years (range 21-93 years) operated on between September 1997 and March
      2001 by means of PFN. The group comprised 11 unstable peritrochanteric fractures
      (31-A2), 26 high subtrochanteric fractures (31-A3), 3 low subtrochanteric
      fractures and 1 pathological fracture. METHOD: Monitored were first of all
      preoperative and post-operative complications and final results. RESULTS: The
      average duration of surgery was in the whole group of 41 patients 61 minutes (30
      100 minutes), in the group of high subtrochanteris fractures 58 minutes (30-80
      minutes). Average X-ray exposure including the time necessary of the reduction of
      the fracture was 2.9 minutes (1-6 minutes). In the group there occurred 3
      complications. In the first case distal fixation of the mail failed. However, the
      fractures healed with any other complications. The second case was a patient with
      unstable peritrochanteric fracture when a too short lag screw was inserted to the
      head during surgery. In spite of this the fracture healed in 3 months, however,
      the resulting varus deformity caused a 1.5 cm shortening of the limb. In the
      third case, a female patient with a low subtrochanteric fracture, fragments were
      left in distraction and a large fragment of medial cortex bearing also lesser
      trochanter remained significantly displaced. Even after 6 months the fractures
      did not healed and therefore we performed dynamization of the nail and cancellous
      bone grafting in the region of the defect of medial cortex. Final results were
      evaluated in patients with a minimum follow-up of 6 months, i.e. in 22 patients,
      9 patients did not come, 8 patients died. Most patients healed in 3 months (in
      total 20 patients of 28 followed up) but we set the minimum follow-up period of 6
      months when we checked 22 patients of 39. Within six months 8 patients died and
      another 9 patients did not appear for the follow up. There were 17 cases of a
      high subtrochanteric fracture, 3 cases of unstable peritrochanteric fracture, one
      case of per-subtrochanteric fracture and one case of a low subtrochanteric
      fracture. Within 6 months the fracture healed in 21 patients, i.e. in 95% of the
      followed-up patients, of this in 20 cases (91%) in anatomical position.
      DISCUSSION: In literature we have found only one publication (Simmermacher et al.
      -Injury 30, 1999) dealing with PFN which presents very good experience with this
      implant. Our good results were significantly influenced by preceding experience
      in the use of Gamma nail. In comparison with it PFN represents an implant of the
      next generation. However, the basic prerequisite of a good result is a perfect
      mastering of the surgical technique. CONCLUSION: PFN is a method of choice in
      trochanteric fractures, namely in high subtrochanteric fractures (31-A3).

PMID- 11951564
TI  - Osseous integration of hydroxyapatite grafts in metaphyseal bone defects of the
      proximal tibia (CT-study).
AB  - PURPOSE OF THE STUDY: The purpose of the study was the examination of the osseous
      integration of hydroxyapatite grafts used for the filling of metaphyseal bone
      defects in tibia head fractures. MATERIAL: Four patients with lateral tibia
      plateau fractures AO-type B3 (12) were included in the study. Patients were
      treated by arthroscopically assisted reduction and percutaneous screw fixation.
      The metaphyseal bone defects were filled with prepared solid hydroxyapatite graft
      blocks (Endobon Fa. Merk Darmstadt, Germany). In all of the patients a CT study
      for the osseous integration of hydroxyapatite grafts used for the filling of
      metaphyseal bone defects in tibial head fractures was performed. Measurements of
      density were performed of the implant region, the periimplant region, the distant
      periimplant region and the fibula bone. Follow-up CT examinations of these
      specific regions were performed 6 and 12 months postoperative. RESULTS: In all
      cases an increase of density of the hydroxyapatite graft after 6 months and 12
      months follow-up was detected. The periimplant region showed in all cases a
      decrease of density. A progressive decrease of the periimplant and the distant
      cancellous tibial bone region was also detectable after 6 and 12 months post-op.
      A similar decrease of density was visible in the region of the cancellous bone of
      the fibula. In the interface region a direct bone formation between the
      hydroxyapatite graft and the adjected cancellous bone was visible in all cases
      during follow-up. CONCLUSION: The increase of density of the hydroxyapatite
      grafts and the direct bone formation in the interface region between the
      hydroxyapatite graft and the adjacent cancellous bone are clear
      radiomorphological signs for an osteointegration of hydroxyapatite grafts in the
      metaphyseal region.

PMID- 11951566
TI  - [Fractures of the femoral neck in children: complications and their treatment].
AB  - PURPOSE OF THE STUDY: Fractures of femoral neck in children are rare skeletal
      injuries which are, however, associated with a high percentage of complications.
      The aim of the retrospective study is to evaluate a group of patients in relation
      to the incidence of individual complications and demonstrate the methods used for
      the solution of these complications. MATERIAL: Twenty patients with fractures of
      femoral neck (average age 10 years 5 months) were treated at the Department of
      the authors in the period between 1983 and 1997. Of this 18 patients were
      operated on (most frequently used was internal fixation by 2 cancellous screws).
      In the given period 10 complications in total were handled of which 3 patients
      were admitted to the Department due to a complication which occurred after the
      surgical treatment of the fracture at another department. The group included
      neither pathological fractures nor patients with hormone-based slipped capital
      femoral epiphysis. METHODS: Fresh fractures of femoral neck were classified after
      Boitzy or Delbet-Collona. The results of the treatment of both fresh fractures
      and complications were evaluated after the interval of more than three years.
      RESULTS: Of 20 cases treated primarily at our Department 13 patients healed
      completely. Complications occurred in 10 cases (43.5% of all treated cases). The
      most frequent complication was avascular necrosis of femoral head (17.4% of all
      treated cases). This complication was managed twice by proximal femoral
      osteotomy, and once by arthrodesis of the hip joint and once by a triple pelvis
      osteotomy. The evaluation of complications shows that the more medial the neck
      fractured the greater was the risk of the incidence of some complication.
      DISCUSSION: The percentage of individual types of fractures is comparable with
      the results presented in the cited works, only Cheng presents an unusually share
      of fractures of type II to the debridement of type III. The incidence of
      avascular necrosis is relatively lower in the given group as compared to the
      cited works (Mayr states 34.6% in patients operated on). Similarly skeptical is
      the evaluation of fractures of type I also in other authors (Pape). CONCLUSIONS:
      The authors recommend as a method of choice in these fractures an early surgical
      treatment with emphasis on exact anatomical reduction of fragments combined with
      intraarticular decompression by arthrotomy in case of the presence of
      hemarthrosis.

PMID- 11951567
TI  - [Are screws in anterior cervical fusion with bicortical fixation truly inserted
      bicortically? Retrospective study].
AB  - PURPOSE OF THE STUDY: To examine the exact position of screws in anterior
      cervical fusion that were intended to be bicortically anchored at the time of
      surgery. MATERIAL: A randomly selected, representative sample (26) of our patient
      series undergoing anterior cervical fusion with bicortical screw fixation (250)
      during period of 1993-1999 is reviewed in this study with respect to an exact
      position of the tips of the screws to the posterior vertebral cortex. A total of
      109 screws were assessed. METHODS: The position of 109 screws was assessed using
      an axial CT scan. On the basis of the distance of the screw tip from the
      posterior cortex of the vertebra, the screws were divided into several
      categories: mono- and bicortically anchored. Bicortically inserted screws were
      statistically evaluated using the confidence interval. RESULTS: Statistical
      analysis shows that the confidence interval of the screws being bicortically
      anchored lies between 66.7 and 87.5% (alpha value = 0.01). No screw was
      introduced more than 3 mm behind the posterior vertebral cortex. Monocortical
      introduction more than 1.5 mm in front of the cortex was observed in 7 screws
      (6.4%) in lower cervical spine and cervico-thoracic junction. DISCUSSION: All the
      screws that were classified as being too short were introduced in the cervico
      thoracical junction or lower cervical spine known for its reduced X-ray
      transparency. The majority of screws, primarily described as bicortical, indeed
      penetrated both vertebral cortices. Considering the results of confidence
      interval for bicortical screw anchoring we conclude that 1 of 4 screws in
      monosegmental and 2 of 6 screws in bisegmental stabilization could fail to be
      bicortically inserted. CONCLUSION: [corrected] Intraoperative methods used for an
      accurate and safe bicortical screw insertion during anterior cervical fusion,
      i.e. intraoperative fluoroscopy, peak insertion torgue of the screw and the
      length measurement of the taped screw canal, are reliable enough to fulfill these
      goals.

PMID- 11951569
TI  - [Personal experience with the basal wedge closed osteotomy of the first
      metatarsus in hallux valgus].
AB  - PURPOSE OF THE STUDY: The authors present their philosophy of the surgical
      treatment of metatarsus primus varus by oblique basal closed osteotomy of 1st
      metatarsal, evaluate and generalize the results achieved also with regard to the
      age of patients. MATERIAL: The evaluation covers a group of patients operated on
      for the mentioned static defect since 1995 with a minimal interval of 12 months
      after the surgery. From this general group a subgroup has been subsequently
      singled out of children and adolescents up to the age of 18. The general group
      included 24 patients in which 31 surgeries were performed. The subgroup of
      children and adolescents comprised 10 patients in which the surgery was performed
      in 12 feet. METHODS: Monitored in both group was age, sex, osteotomy laterality,
      the presence of distal operation. Post-operative monitoring focussed on the
      following data: the time interval after the operation, subjective satisfaction,
      range of motion of Ist metatarsophalangeal joint, the incidence of complications.
      Evaluation covered post-operative correction of individual angles and the
      shortening of Ist metatarsal by comparison of pre- and post-operative radiograph.
      RESULTS: Evaluated in the whole group were 22 patients, in the group of children
      and adolescents 8 patients, with average time interval of 3 years after the
      operation. On the basis of the surgery average correction of intermetatarsal
      angle by 10.5 degrees was achieved in both groups, average correction of
      valgosity by 18 degrees in the basic group and by 10 degrees in the group of
      adolescents. DISCUSSION: The results are evaluated globally on the basis of
      specialized literature. The authors present their philosophy of the solution of
      the issues of metatarsus primus varus as a static defect by different surgical
      techniques, formulate a clear strategy of the use of distal surgery and discuss
      its efficiency in relation to the patient's age. CONCLUSION: Oblique basal closed
      osteotomy of Ist metatarsal within a comprehensive solution of the static defect
      of hallux valgus is recommended to the broad orthopaedic public as a surgery
      which in view of the authors can bring good results in children and adolescents.
      In adults they recommend to indicate this surgery in the mentioned cases in
      combination with a distal operation.

PMID- 11951568
TI  - [Mortality in patients with proximal femoral fractures during the first year
      after the injury].
AB  - PURPOSE OF THE STUDY: The authors present an overview of mortality of patients
      with proximal femur fractures treated at the authors' Department in 1997 in
      dependence on different factors relating to the preinjury condition and the
      treatment itself. The aim of the work was to determine the impact of these
      factors on the risk of mortality and compare the findings with the data published
      by other authors dealing with the same issue. MATERIAL: In the given year 244
      patients with 248 proximal femur fractures, 58 men (24%), 186 women (76%),
      average age 77 years were treated. There were 115 (47%) fractures of femoral
      neck, 117 (47%) pertrochanteric fractures and 16 (6%) intertrochanteric (high
      subtrochanteric) fractures. Thirty-nine fractures (16%) were treated
      conservatively, internal fixation was performed in 116 fractures (47%), i.e. 6
      times by a plate, 94 times by a DHS, 16 times by the Gamma nail, and 93 fractures
      (37%) were treated by arthroplasty (62 times by hemiarthroplasty and 31 times by
      total hip arthroplasty). METHODS: The following data was recorded in all patients
      of the monitored group: age, sex, social environment and physical activities of
      the patient prior to the injury, mechanism of the injury, type of fracture,
      surgical risk expressed by the respective class of the ASA score, therapeutic
      procedure, type of anesthesia and interval between the injury and operation.
      Recorded was also the number of mortality in the course of primary
      hospitalisation and one year after the injury or operation. At the end of the one
      year monitoring statistical evaluation was made of the relation between mortality
      and the above mentioned monitored factors and the results were compared with
      those published in similar types of study. RESULTS: In the period of one year
      after the injury or operation 85 patients died of the total number of 244 (56
      women and 29 men). The number of decreased patients was increasing in individual
      age decades and the highest number was recorded in case of men in 9th decade
      (80%) and 10th decade (100%). The lowest number of mortality related to patients
      who lived with their families prior to the injury (26.5%) and the highest number
      was in patients from social care institutes (43.8%). Patients with impaired
      mobility already prior to the injury and not leaving their homes accounted for
      46.7% of mortality. In the course of one year after the injury 33.0% died of
      fracture of femoral neck, 30.7% of pertrochanteric and 35.7% of intertrochanteric
      (high subtrochanteric) fracture. Dependence of mortality on ASA score was as
      follows: ASA I-0%, ASA II-4.3%, ASA III-21.3%, ASA IV-42.1%, ASA V-68.9%. The
      highest number of mortality of operated on patients was in the group treated by
      hemiarthroplasty (41.1%). After spinal anesthesia 26.6% of patients died within
      one year and after general anesthesia 26.7% of them. There was an evident
      increase in the number of mortality in patients operated on in the interval
      longer than 3 days after the injury. DISCUSSION: The mortality in the followed up
      group was statistically significantly influenced by the age (p = 0.003), sex (p <
      0.01) and ASA score (p < 0.001). This corresponds to the results of other
      studies. The dependence of mortality on environment and mobility prior to the
      injury, type of the fracture, type of surgical treatment and type of anesthesia
      has not been proved. CONCLUSION: Based on the evaluation of the data monitored in
      the group a conclusion was made that absolute mortality risk in the first year
      after the injury related to patients with pathological fractures due to
      metastasis. A higher risk related to male patients older than 80 years with the
      surgical risk of ASA IV and higher and this risk rate was the highest in the time
      interval within 3 months after the injury or operation.

PMID- 11951570
TI  - [Atlanto-axial rotation dislocation (case report)].
AB  - The authors present a female patient 45 years old, who had a car accident as a
      driver of a passenger car. Her car was hit from the left side by another car and
      the women hurt her head, neck and left shoulder. Due to pain in the region of the
      head and neck she was taken to the respective surgical out-patient department
      where they diagnosed the concussion of the brain of II degree and distortion of
      the cervical spine. The patient was treated conservatively by bed rest with the
      cervical spine fixed in the soft Schanz collar. After ten days she was discharged
      from the hospital and further followed up by a neurologist in the out-patient
      department. She underwent physical therapy focussed on the relaxation of muscles
      in the region of the cervical spine. Due to persisting pain in the region of
      upper cervical spine the patient was sent to the department of the first author
      six weeks after the injury. On clinical examination the head was inclined to the
      right and rotated to the left with pain in the region of the occipitocervical
      passage. Radiographs were made in the lateral and Sandberg projection. In the
      lateral projection the atlantodental distance was normal, the Sandberg projection
      showed an evidently asymmetrical location of the dens between the lateral masses
      of the atlas, asymmetrical size of the lateral masses and inclination of the head
      to the left. These basic projections alone showed an evident rotational
      atlantoaxial dislocation of I degree according to Fielding. The authors further
      added CT examination which showed rotation of C1 against C2 and asymmetrical
      location of the dens without dislocation from the anterior arch of the atlas. A
      conservative physical therapy was not successful and the patient felt worse.
      Twelve months after the injury a pre-operative traction by Glisson sling was
      introduced for five days with a gradual weight bearing up to 5 kg. A reduction
      followed from the dorsal approach and fixation of C1-C2 after Magerl combined
      with Gallie technique. The surgery was without complications and the post
      operative radiographs showed a good position of the C1-C2 complex and a correct
      insertion of screws through atlantoaxial joints. The patient wore for six weeks a
      Philadelphia collar and another six weeks the Schanz collar. Standard and
      functional radiographs in flexion and extension made 12 weeks after the surgery
      showed bone bridging between C1-C2 arches and a stable atlantoaxial fusion. At
      the check one year after the surgery the patient had a limited rotation of the
      head by 25%, however, she was without pain and the inclination and rotation of
      the head was compensated. In the authors' view the use of Magerl technique of C1
      C2 fixation is possible in case of a rotational atlantoaxial dislocation but
      difficult with regard to the changed anatomical conditions.

PMID- 11951571
TI  - [Recommendations for a methodologic approach in the diagnosis and therapeutic
      care of occupational diseases of the locomotor apparatus of the extremities due
      to long-term unilateral stress].

PMID- 11951572
TI  - [Cementless socket fixation based on the "press-fit" concept in total hip joint
      arthroplasty].
AB  - PURPOSE OF THE STUDY: The key problem of implant fixation in THR is stress
      distribution, i.e. load transmission between bone and implant. The closer the
      load transfer is to the original physiological situation, the easier the
      adaptation of the periprosthetic bone to the new biomechanical conditions after
      implantation of the cup and the safer is its longlasting fixation. The aims of
      the studies were 1) to get information about the physiological load transfer in
      the normal hip joint, 2) to get information about the load transfer between
      acetabulum and acetabular sockets and vice versa, 3) to measure the
      periacetabular pelvic bone deformation as the stimulator of the remodelling
      process (third stage of osseointegration) in the normal hip joint and in hip
      joints fitted with different acetabular cups, 4) to study the morphological
      stages of osseointegration of a non-cemented press-fit cup and to compare the
      morphological structure of the periacetabular bone with the biomechanical data
      obtained by the in vitro studies and finally, 5) to compare the clinical and
      radiological outcome of follow-up studies of the senior author's "Press-Fit cup"
      with the theoretical hypotheses according to the experimental observations.
      MATERIAL AND METHODS: Load transfer between the acetabular bone and the femoral
      head on one side and press-fit cups has been determined by strain gauge
      measurements, finite element studies, pressure sensitive Fuji prescale films, CT
      osteoabsorptiometry and telemetric measurements. Periacetabular deformation has
      been measured by Imetric Markers. Osseointegration of the senior author's press
      fit cup and, thus, the remodelling process of the bony structures adjacent to the
      cup have been studied in autopsy specimens of THRs which have been in situ for
      several years. RESULTS: Load transfer measurements have shown that the main load
      in the original acetabulum as well as in the acetabulum fitted with a press-fit
      cup is transmitted to the periphery, especially to the acetabular cortical rim
      whereas the subchondral bone is exposed to lower, predominantly meridional
      (tension) stresses. Direct measurements of the periacetabular deformation under
      load revealed an increase of the peripheral press-fit with increasing stability
      of a (oversized) press-fit cup. Both the normal as well as the acetabulum fitted
      with a non-cemented cup deforms in a postero-medial direction. The histo
      morphology of the periacetabular bone of autopsy specimens showed excellent bony
      in- and ongrowth of a porous titanium coating (SULMESH) and bone formation,
      especially at the periphery in zone 1 and 3 according to DeLee and Charnley.
      CONCLUSION: The studies have shown that the subchondral bone plate of the
      acetabulum has very little supportive function for non-cemented press-fit cups.
      For the preparation of the acetabulum it is, therefore, more important to ream
      the sclerotic subchondral bone until there is a well vascularized, well bleeding
      bone bed to facilitate osseointegration of a non-cemented acetabular socket than
      to preserve the subchondral bone plate as is the case in cement fixation. A non
      cemented press-fit socket must transmit load predominantly to the cortical bone
      of the acetabular rim. Therefore, a too far medial positioning of the cup, and
      therefore loosing contact to the cortical rim, must be avoided under all
      circumstances. The clinical experience with acetabular revisions and with
      conversions of hip arthrodeses into a THR (where there is no subchondral bone at
      all) have shown the superiority of a well vascularized over a sclerotic (even
      mechanically stronger) bone bed. Furthermore, it has been shown that the
      additional use of screws for fixation of an acetabular cup is not only
      unnecessary but can be deleterious and causes complications including osteolysis
      and aseptic loosening.

PMID- 11951573
TI  - Effect of lipase activities of Propionibacterium granulosum and Propionibacterium
      acnes.
AB  - We studied the lipase activities of Propionibacterium granulosum, P. acnes and
      the suppression of these activities by Jumi-haidoku-to (JHT). Lipase activity of
      P. acnes biotype III (BIII) was strongest, while that of P. granulosum was
      faintly expressed. Compared with the control medium, the production of propionic
      and butyric acids was suppressed by all the tested mediums combined with JHT. The
      decrease in these acids produced by JHT was significantly higher in P. granulosum
      than in P. acnes. Although P. acnes BIII may produce a strong effect on acne, the
      presence of P. granulosum should not be ignored. Further research is required on
      the correlation between P. acnes and P. granulosum.

PMID- 11951574
TI  - Mucopolysaccharides from psyllium involved in wound healing.
AB  - Mucopolysaccharides derived from the husk of psyllium (Plantago ovata) have
      properties beneficial for wound cleansing and wound healing. Recent studies
      indicate that these mucopolysaccharides also limit scar formation. Our in vitro
      and in vivo studies aimed to investigate the mechanisms involved, e.g., fluid
      absorption, bacterial adherence and in vitro stimulatory effects on macrophages,
      which are pivotal in wound healing. The mucopolysaccharides contained in a sachet
      (Askina Cavity) or in a hydrocolloid mixture (Askina Hydro) were found to have a
      gradual and sustained absorbency over a period of 7 days, amounting to 4-6 times
      their weight in water. The swelling index was 9 mm after 312 h. Adherence of
      wound bacteria to the mucopolysaccharides started after 2 h and was more
      pronounced after 3 h. Semiquantitative measurements of bacterial adherence used
      centrifugation and subsequent optical density determinations of supernatant.
      These confirmed the strong adherence potential of psyllium particles. Lactic acid
      dehydrogenase staining of pretreated cultured human skin explants did not reveal
      toxicity of the mucopolysaccharides derived from psyllium husk. Langerhans' cell
      migration from the epidermis was negligible and interleukin-1 beta expression in
      the explants was not significant, supporting the very low allergenic potential of
      psyllium. The characteristics of mucopolysaccharide granulate derived from
      psyllium husk in Askina Cavity and Askina Hydro related to fluid absorption,
      bacterial adherence, biocompatibility, stimulation of macrophages, irritancy
      response and allergenicity showed an optimal profile, supporting the good
      clinical performance of wound healing products containing psyllium husk.

PMID- 11951575
TI  - Noninvolvement of hypertriglyceridemia and hyperleptinemia in blood pressure
      increases induced by dietary lard in rats.
AB  - We investigated whether hypertriglyceridemia and hyperleptinemia are involved in
      the development of increases in blood pressure induced by dietary lard. Rats
      received either chow alone or chow in which 50% of the energy content was from
      substituted lard. Each group was divided into two groups according to whether the
      diet included bezafibrate or not. In another series of experiments, rats were fed
      either chow alone or chow in which 50% of the energy content was from substituted
      lard, safflower oil, or sucrose. Systolic blood pressure (SBP) was measured every
      week during each 7-week feeding period. A steady-state plasma glucose method was
      used to determine insulin sensitivity after lard substitution with or without
      bezafibrate. After the 7-week feeding period, the plasma levels of glucose,
      immunoreactive insulin, triglyceride and leptin were measured. In rats fed with a
      high lard diet, SBP, plasma levels of immunoreactive insulin, triglyceride,
      leptin and steady-state plasma glucose concentrations significantly increased,
      compared with levels of these substances in controls. Bezafibrate treatment
      completely reversed these effects. In rats fed with a high safflower oil or a
      high sucrose diet, no significant change was seen in SBP and plasma
      immunoreactive insulin levels. However, the plasma triglyceride levels were
      increased by dietary lard or sucrose. Moreover, the plasma leptin level was also
      increased by dietary lard and safflower oil. Neither dietary hypertriglyceridemia
      nor hyperleptinemia were involved in the development of increases in blood
      pressure induced by dietary lard.

PMID- 11951576
TI  - Rise in plasma leptin levels after stimulation of hypothalamic cholinoceptive
      neurons by neostigmine in rats.
AB  - To investigate the role of hypothalamic cholinergic neurons in the regulation of
      plasma leptin levels, we injected neostigmine, a cholinesterase inhibitor, or
      vehicle alone into the third cerebral ventricle in free moving male Wistar rats
      and then measured plasma leptin levels. The administration of neostigmine (5 x
      10(-9) or 5 x 10(-8) mol) increased plasma leptin levels 3-6 h after stimulation
      in a dose-dependent manner, while intravenous injection of neostigmine (5 x 10(
      8) mol) had no effect. Atropine (5 x 10(-8) mol) concomitantly injected with
      neostigmine (5 x 10(-8) mol) prevented neostigmine-induced increase in plasma
      leptin. The expression of leptin messenger ribonucleic acid (mRNA) in epididymal
      white adipose tissue was significantly increased at 4 and 6 h after neostigmine
      injection compared with that before the injection. Plasma levels of
      corticosterone were significantly increased at 30 min after stimulation with
      neostigmine and this increase was sustained for 6 h after stimulation.
      Furthermore, bilateral adrenalectomized rats showed no increase in plasma leptin
      levels after stimulation. In conclusion, stimulation of hypothalamic
      cholinoceptive neurons increased plasma leptin levels in rats by increasing
      leptin production in adipocytes. This increase may be due to an increase in
      glucocorticoids from the adrenal glands. These results suggest that plasma leptin
      levels can be regulated by hypothalamic cholinoceptive neurons.

PMID- 11951577
TI  - Age-related differences in forced walking stress-induced analgesia in mice.
AB  - We investigated the effects of aging on forced walking stress-induced analgesia
      using a formalin-induced paw licking test in male mice. Exposure to forced
      walking stress for 6 h showed forced walking stress-induced analgesia in all mice
      aged 4, 24 and 48 weeks in the second phase (10-30 min), but not in the first
      phase (0-10 min). In the second phase, the degree of stress-induced analgesia was
      age-dependent (4 > 24 > 48 weeks). LY-235959, a competitive N-methyl-D-aspartate
      (NMDA) receptor antagonist, blocked forced walking stress-induced analgesia in
      mice aged 4 and 24 weeks, but not in those aged 48 weeks. Naloxone did not
      antagonize forced walking stress-induced analgesia in mice in any of the age
      groups. The present study suggests that the degree of forced walking stress
      induced analgesia depends on the age of mice and confirms previous findings that
      forced walking stress-induced analgesia is involved in the nonopioid system via
      NMDA receptors.

PMID- 11951578
TI  - Evaluation of efficacy and tolerance of neuramide in the treatment of herpes
      zoster and postherpetic neuritis.
AB  - Ninety-two patients suffering from herpes zoster were enrolled in a double-blind
      controlled study aimed at evaluating the efficacy and tolerance of the drug
      neuramide. Neuramide (N) and placebo (P) were administered to patients
      intramuscularly twice daily for 28 days as follows: group N + N (patients always
      treated with neuramide); group N + P (patients treated with neuramide for 1 week,
      then with placebo); group P + N (patients treated with placebo for 1 week, then
      with neuramide); group P + P (patients always treated with placebo). During the
      first week, all patients were also treated with standardized doses of acyclovir.
      The presence and extent of clinical symptoms were evaluated during the first 4
      weeks, while the appearance, degree and duration of postherpetic neuralgia were
      evaluated both during treatment and over a 6-month follow-up period. There were
      no significant differences between the four groups of patients when subjective
      parameters (such as pain and paresis at the lesion site) were examined. However,
      clinical examination at the end of treatment showed that treatment with neuramide
      was therapeutic. Indeed, the times for recovery and for regeneration of
      epithelium were significantly shorter when neuramide was administered for 3 weeks
      of the treatment period. Furthermore, the change from vesicles to crusts was
      significantly faster in the neuramide group than in the placebo group.
      Postherpetic neuritis occurred in the first months of follow-up. However, in
      groups N + P and P + P, the symptoms lasted throughout the 6-month observation
      period, while in the other groups this period was shorter. Indeed, there were
      significant differences (p < 0.05) in terms of the above complications between
      the following groups: N + N and N + P; N + N and P + P; N + P and P + N; P + N
      and P + P. No significant differences were observed between the N + N and P + N,
      or N + P and P + P groups. Taken together, these data demonstrate that neuramide
      treatment for at least 3 weeks significantly reduces the risk of postherpetic
      neuritis development.

PMID- 11951579
TI  - Treatment of knee osteoarthritis with a topical non-steroidal antiinflammatory
      drug. Results of a randomized, double-blind, placebo-controlled study on the
      efficacy and safety of a 5% ibuprofen cream.
AB  - The efficacy and safety of a 5% ibuprofen cream (Dolgit cream) in primary knee
      osteoarthritis was assessed in this double-blind, randomized, placebo-controlled,
      parallel-group study with an adaptive sequential design. The background of the
      study was the need to confirm the efficacy of ibuprofen cream. Patients aged 40
      75 years, with a visual analog scale (VAS) score of pain on motion of 40 mm, a
      Lequesne index score of 5-13 points, and a Kellgren and Lawrence radiographic
      score of grade II-III were enrolled between September 1999 and November 2000. The
      study medication was applied in a 10-cm strip t.i.d. for 7 days on the more
      painful knee. In the active group, each strip contained approximately 200 mg
      ibuprofen. The main outcome measure was the response rate to the treatment
      compared between both groups. Response was defined as a reduction of pain on
      motion, self-assessed on a VAS, of > or = 20 mm compared with baseline. The
      planned interim analysis after inclusion of 2 x 50 patients showed a response
      rate of 32 (64.0%) in the ibuprofen group and 15 (30.0%) in the placebo group (p
      = 0.000615). The study could then be terminated. All secondary endpoints, pain at
      rest, pain on pressure, Lequesne index and overall assessment, also confirmed the
      statistically significant differences between the groups. No drug-related adverse
      events were recorded. The study confirmed the efficacy of ibuprofen cream by
      demonstrating its statistically significant and clinically relevant superiority
      over the placebo cream in the treatment of primary knee osteoarthritis.

PMID- 11951580
TI  - Hymecromone in the treatment of motor disorders of the bile ducts: a multicenter,
      double-blind, placebo-controlled clinical study.
AB  - Biliary dyskinesia is frequently encountered in clinical practice and is
      characterized by pain during or after meals. The present study was designed to
      assess the action of hymecromone in patients with motor disorders of the bile
      ducts. One hundred twenty-three patients (36 men and 87 women) were enrolled in
      the multicenter double-blind placebo-controlled study. The mean age was 60.3
      years +/- 14.2 SD. Diagnosis was dyspepsia in 58 patients, dyskinesia in 59,
      cholelithiasis in five and hepatopathy in one. The patients were divided into two
      groups. One group (61 patients) was treated with hymecromone (300 mg tablets at a
      dosage of 1,200 mg/day, 2 tablets midday and evening) and another group (62
      patients) was treated with placebo. Treatment lasted for 14 days. Control of
      dyspepsia and pain symptoms of biliary origin was more marked and constant with
      hymecromone than with placebo. By the end of the treatment, patients in the
      hymecromone group showed a 70.3% reduction in intensity of spontaneous abdominal
      pain, while the placebo group showed a 43.8% reduction. Hymecromone was well
      accepted by the patients and judged to be effective by the investigator in 88.5%
      of patients treated. The possibility of using hymecromone in 300-mg tablets in
      the treatment of motor disorders of the bile ducts is thus confirmed.

PMID- 11951581
TI  - Benefits of resveratrol in women's health.
AB  - Resveratrol and trans-resveratrol are powerful phytoestrogens, present in the
      skins of grapes and other plant foods and wine, which demonstrate a broad
      spectrum of pharmacological and therapeutic health benefits. Phytoestrogens are
      naturally occurring plant-derived nonsteroidal compounds that are functionally
      and structurally similar to steroidal estrogens, such as estradiol, produced by
      the body. Various studies, reviewed herein, have demonstrated the health benefits
      of phytoestrogens in addressing climacteric syndrome including vasomotor symptoms
      and postmenopausal health risks, as well as their anticarcinogenic,
      neuroprotective and cardioprotective activities and prostate health and bone
      formation promoting properties. Conventional HRT drugs have been demonstrated to
      cause serious adverse effects including stroke and gallbladder disease, as well
      as endometrial, uterine and breast cancers. Recent research demonstrates that
      trans-resveratrol binds to human estrogen receptors and increases estrogenic
      activity in the body. We investigated the effects of protykin, a standardized
      extract of trans-resveratrol from Polygonum cuspidatum, on cardioprotective
      function, the incidence of reperfusion-induced arrhythmias and free radical
      production in isolated ischemic/reperfused rat hearts. The rats were orally
      treated with two different daily doses of protykin for 3 weeks. Coronary
      effluents were measured for oxygen free radical production by electron spin
      resonance (ESR) spectroscopy in treated and drug-free control groups. In rats
      treated with 50 and 100 mg/kg of protykin, the incidence of reperfusion-induced
      ventricular fibrillation was reduced from its control value of 83% to 75% (p <
      0.05) and 33% (p < 0.05), respectively. Protykin was seen to possess
      cardioprotective effects against reperfusion-induced arrhythmias through its
      ability to reduce or remove the reactive oxygen species in ischemic/reperfused
      myocardium. Taken together, these data suggest that trans-resveratrol
      supplementation may be a potential alternative to conventional HRT for
      cardioprotection and osteoporosis prevention and may confer other potential
      health benefits in women.

PMID- 11951582
TI  - Determination of the chemical composition of the nutritionally valuable parts of
      male and female common west African fresh water crab Sudananautes africanus
      africanus.
AB  - The proximate and mineral composition of the anatomical parts of adult male and
      female Sudananautes africanus africanus (common West African fresh water crab)
      were determined. The mineral composition of the ambient water was also
      determined. The lifeweights of the males varied between 92.18 and 140.36 g and
      the values ranged between 56.95 and 102.61 g in the females. The cheliped muscle
      recorded the highest value for protein and the lowest value for the total ash in
      both sexes, correlation coefficients (rMF) were positively related and high for
      protein (0.99), crude fat (0.84), total ash (0.99) and fibre (0.99) but
      negatively related in carbohydrate (-0.49) between the two sexes. The following
      minerals were highly concentrated in both sexes: Ca, Mg, Zn, Ni, P, Fe, Cu, Na
      and K with significant differences occurring in Ca, Mg, Zn, Ni, P, Fe, Cu and K
      at alpha < 0.05. Bioconcentration factors were found to be particularly high in
      the trace heavy metals: Co, Ni and Cu. All the various parts studied were found
      to be very good sources of the minerals examined with the exception of Co.

PMID- 11951583
TI  - Vitamin profile of cooked foods: how healthy is the practice of ready-to-eat
      foods?
AB  - During recent years importance of B complex vitamins, beta-carotene and vitamin C
      has been realised in terms of their antioxidative and anticarcinogenic
      properties. Fruits and vegetables are the rich sources of these vitamins.
      However, there are considerable cooking losses of vitamins, and information on
      vitamin contents of cooked foods is essential for assessing the adequacy of
      vitamin intakes. Secondly, there is a growing trend to consume ready-to-eat foods
      such as stuffed pancakes (samosa, patties), pastries, French fries; replacing
      traditional foods for lunch or dinner like roti, vegetable curry, bread, non
      vegetarian items. Ready-to-eat foods are considered to give empty calories rather
      than a balanced diet. A study was undertaken to estimate ascorbic acid, folic
      acid, riboflavin, thiamine and beta-carotene of 263 cooked food samples and 260
      meals representing dietary patterns of Asia, Africa, Europe, USA and Latin
      America by spectrophotometry and photoflurometry. A broad range of beta-carotene
      (84-2038 mcg%), riboflavin (0.01-0.48 mg%), thiamine (0.04-0.36 mg%), vitamin C
      (1-28 mg%) and folate (26-111 mcg%) was observed in individual foods. Bakery
      products and sweets were found to be poor sources and green leafy vegetables and
      fruits were good sources of these five vitamins. The differences between ready-to
      eat foods and meals consumed during lunch or dinner were prominent for beta
      carotene, ascorbic acid, riboflavin and folic acid (P < 0.05). The cooking losses
      were 34.6, 30, 52.2, 45.9 and 32.2% in case of ascorbic acid, thiamine,
      riboflavin, beta-carotene and folic acid respectively. Irrespective of whether it
      is ready-to-eat or a lunch/dinner food item, the contribution of vegetables in
      the preparations was found to make a marked impact on the vitamin profile. While
      results justify the concept of a food pyramid, emphasis needs to be given to
      types of fruits and vegetables rich in vitamins; preferably in their uncooked
      form, rather than considering their total consumption.

PMID- 11951585
TI  - The importance of bee-collected pollen in the diet: a study of its composition.
AB  - In this article the content of macronutrients and the calorific value of 15
      commercial samples of pollen is presented. This bee-collected product can be a
      good complement to our daily diet due to the interesting proportions of proteins,
      fats and carbohydrates, especially these last two.

PMID- 11951584
TI  - Bottle wars: England versus Scotland versus France.
AB  - Four batches of four brands of bottled water from England, Scotland and France
      were tested for their microbiological and physicochemical characteristics during
      a 2-month study. The lowest priced brand of water had the highest nitrate content
      (46.9 mg/L), while the most expensive brand did not necessarily have the best
      values for pH, total dissolved solids, turbidity or plate count. While no sample
      was positive for E. coli, the range of other measured values varied widely
      between brands and batches during the study. The bottled water samples from
      France on average demonstrated better results than the other countries studied.

PMID- 11951586
TI  - Use of non-crop food vascular plants in Montseny biosphere reserve (Catalonia,
      Iberian Peninsula).
AB  - An ethnobotanical survey was carried out in the massif of Montseny (Catalonia,
      Iberian Peninsula), a mountainous UNESCO's biosphere reserve that summarizes the
      main European (from Mediterranean to subalpine) climates and landscapes. This
      article presents the results concerning the use of non-crop vascular food plants,
      numbering 132. Edible plants (75), as well as those involved in drink preparation
      (84) are considered. The study shows the different ways of preparation,
      preservation and consumption of plants. Most food plants also have uses as folk
      medicines in the region considered, and the relationships between foods and
      medicines are discussed. The presence and usage of wild relatives of cultivated
      plants in the territory studied are also commented upon.

PMID- 11951587
TI  - Protein-lipid interactions in food systems: a review.
AB  - Proteins and lipids, both individually or as complexes, play important functional
      roles in foods. Since the 1970s food scientists have devoted attention to the
      nature of these interactions and particularly to their effects on functional
      characteristics of protein-based foods. Previously, most of the published work
      was devoted to the biochemical aspects of protein-lipid interactions in
      biological systems. This article reviews the protein-lipid interactions of both
      naturally occurring protein-lipid complexes and protein-lipid complexes formed by
      induced interactions in foods and food products. The physicochemical
      characteristics of known protein-lipid complexes, the nature of binding which
      results in formation of these complexes and the effect of the interactions on
      food functionality are reviewed.

PMID- 11951588
TI  - Measurement of surface area, gel weight and saliva weight in a gelatin-based gel
      over the course of mastication.
AB  - The aim was to devise a method for the measurement of total surface area and
      weight, as well as saliva weight, for a gelatin-based confectionery gel over the
      course of human mastication for input into separate modelling of flavour release.
      The method is based on an alcohol rinse to remove saliva, followed by immersion
      in amaranth dye to give a thin surface dye layer coating the gel fragments. Total
      surface area is then found by measurement of quantity of absorbed dye. The
      resulting time profiles for the six panellists showed that surface area reached a
      maximum of 3000 mm2 with the 4.28 g gel weight being consumed over 41 to 64 sec
      with differing numbers of swallows (4-6) and chews (52-103). Calculated total
      relative saliva weights, 498-993 g kg-1, and flow rates, 2.8-5.6 g min-1, were
      towards the upper range of those reported in the literature.

PMID- 11951589
TI  - Design and analysis of food frequency questionnaires--review and novel method.
AB  - A novel method is proposed for the design and analysis of a food frequency
      questionnaire facilitated by a computer program. The method relies on a weighed
      inventory undertaken by a sample of the population that is combined into a
      database along with the nutrient analyses of the foods consumed. The program
      provides an interface that enables the researcher to see the total amount of each
      food that was consumed, decide on what questions to ask and allocate the relevant
      foods to these questions. The approach means that all foods consumed can appear
      in the questionnaire. The nutrient analysis for each question is a weighted mean
      depending on the inventory. The portion weight employed for each question is
      derived from the weights of foods consumed in the inventory and any
      misperceptions in the frequency of consumption of all the subjects are corrected
      by calculating a factor to multiply by the frequency from the questionnaire. A
      viability study established the practicability of the method.

PMID- 11951590
TI  - Dear specialist: please don't dump your job on me.

PMID- 11951592
TI  - Set up your home office the right way.

PMID- 11951591
TI  - Dump a health plan? How to decide.

PMID- 11951593
TI  - The ABCs of courage.

PMID- 11951594
TI  - Find a billing boss who fits the bill.

PMID- 11951595
TI  - Malpractice. Don't wait for a lawsuit to strike.

PMID- 11951596
TI  - Will the Good Samaritan Law protect you?

PMID- 11951597
TI  - A weary Shepherd.

PMID- 11951598
TI  - Introduction to telomeres and telomerase.

PMID- 11951599
TI  - Standard TRAP assay.

PMID- 11951600
TI  - Stretch PCR assay.

PMID- 11951601
TI  - Detection of chromosome ends by telomere FISH.

PMID- 11951602
TI  - Fluorescent detection of telomerase activity.

PMID- 11951603
TI  - Nonradioactive detection of telomerase activity using a PCR-ELISA-based telomeric
      repeat amplification protocol.

PMID- 11951604
TI  - In Situ TRAP assay detection of telomerase activity in cytological preparations.

PMID- 11951605
TI  - Biotinylated primer for detecting telomerase activity without amplification.

PMID- 11951606
TI  - Whole-cell and microcell fusion for the identification of natural regulators of
      telomerase.

PMID- 11951607
TI  - Screening with COMPARE analysis for telomerase inhibitors.

PMID- 11951608
TI  - Telomerase as a therapeutic target. Therapeutic potential of telomerase
      inhibitors.

PMID- 11951609
TI  - Telomere length distribution. Digital image processing and statistical analysis.

PMID- 11951610
TI  - Analysis of telomerase RNA gene expression by in situ hybridization.

PMID- 11951611
TI  - Relative gene expression in normal and tumor tissue by quantitative RT-PCR.

PMID- 11951612
TI  - Quantitative detection of telomerase components by real-time, online RT-PCR
      analysis with the LightCycler.

PMID- 11951613
TI  - Analysis of cell generation in the telencephalic neuroepithelium.

PMID- 11951614
TI  - Clonal analyses and cryopreservation of neural stem cell cultures.

PMID- 11951616
TI  - Detection of telomerase activity in neural cells.

PMID- 11951615
TI  - Assessing the involvement of telomerase in stem cell biology.

PMID- 11951617
TI  - In vitro assays for neural stem cell differentiation.

PMID- 11951619
TI  - Electron microscopy and lac-Z labeling.

PMID- 11951620
TI  - Techniques for studying the electrophysiology of neurons derived from neural
      stem/progenitor cells.

PMID- 11951618
TI  - Production and analysis of neurospheres from acutely dissociated and postmortem
      CNS specimens.

PMID- 11951621
TI  - Fluorescence in situ hybridization.

PMID- 11951622
TI  - RT-PCR analyses of differential gene expression in ES-derived neural stem cells.

PMID- 11951623
TI  - Differential display. Isolation of novel genes.

PMID- 11951624
TI  - Cell labeling and gene misexpression by electroporation.

PMID- 11951625
TI  - Gene therapy using neural stem cells.

PMID- 11951626
TI  - Modeling brain pathologies using neural stem cells.

PMID- 11951627
TI  - Activation and differentiation of endogenous neural stem cell progeny in the rat
      Parkinson animal model.

PMID- 11951628
TI  - Identification of Musashi1-positive cells in human normal and neoplastic
      neuroepithelial tissues by immunohistochemical methods.

PMID- 11951629
TI  - Identification of newborn cells by BrdU labeling and immunocytochemistry in vivo.

PMID- 11951630
TI  - Isolation of stem and precursor cells from fetal tissue.

PMID- 11951631
TI  - Immunocytochemical analysis of neuronal differentiation.

PMID- 11951632
TI  - Neuroanatomical tracing of neuronal projections with Fluoro-Gold.

PMID- 11951634
TI  - Labeling stem cells in vitro for identification of their differentiated
      phenotypes after grafting into the CNS.
AB  - Labeling stem cells for CNS grafting is an empirical process. Specific protocols
      cannot be given that will work for all cell types and all applications. We have
      provided the range of conditions under which various labels have been
      successfully used in CNS grafting studies, and delineated the parameters that
      have to be empirically established. Given a clear understanding of the
      limitations of the respective labels, and the expected outcome of the grafting
      experiment, these labeling guidelines should enable any investigator to develop a
      successful labeling approach. Our own personal bias is to use labels that cannot
      be transferred to host cells. We prefer BrdU, or more often, retrovirally
      delivered EGFP or lacZ. However, each investigator will have to decide what is
      optimal for their own cell population and experimental design.

PMID- 11951633
TI  - Neural differentiation of embryonic stem cells.

PMID- 11951635
TI  - Optimizing stem cell grafting into the CNS.

PMID- 11951636
TI  - Vision-guided technique for cell transplantation and injection of active
      molecules into rat and mouse embryos.

PMID- 11951637
TI  - Transplantation into neonatal rat brain as a tool to study properties of stem
      cells.

PMID- 11951638
TI  - Routes of stem cell administration in the adult rodent.

PMID- 11951639
TI  - Olfactory ensheathing cells. Isolation and culture from the rat olfactory bulb.

PMID- 11951640
TI  - Culturing olfactory ensheathing glia from the mouse olfactory epithelium.

PMID- 11951641
TI  - Production of immortalized human neural crest stem cells.

PMID- 11951642
TI  - Adult rodent spinal cord derived neural stem cells. Isolation and
      characterization.

PMID- 11951643
TI  - Preparation of neural progenitors from bone marrow and umbilical cord blood.

PMID- 11951644
TI  - Seeding neural stem cells on scaffolds of PGA, PLA, and their copolymers.

PMID- 11951645
TI  - DNA methylation protocols. Overview.

PMID- 11951647
TI  - Isolation of CpG islands using a methyl-CpG binding column.

PMID- 11951646
TI  - Methylated CpG island amplification for methylation analysis and cloning
      differentially methylated sequences.

PMID- 11951648
TI  - Purification of MeCP2-containing deacetylase from Xenopus laevis.

PMID- 11951649
TI  - DNA-methylation analysis by the bisulfite-assisted genomic sequencing method.

PMID- 11951650
TI  - Measuring DNA demethylase activity in vitro.

PMID- 11951651
TI  - Extracting DNA demethylase activity from mammalian cells.

PMID- 11951652
TI  - Measurement of genome-wide DNA cytosine-5 methylation by reversed-phase high
      pressure liquid chromatography.

PMID- 11951653
TI  - Methylation analysis by chemical DNA sequencing.

PMID- 11951654
TI  - Methylation-sensitive restriction fingerprinting.

PMID- 11951655
TI  - Restriction landmark genome scanning.

PMID- 11951656
TI  - Combined bisulfite restriction analysis (COBRA).

PMID- 11951657
TI  - Differential methylation hybridization using CpG island arrays.

PMID- 11951658
TI  - Nearest-neighbor analysis.

PMID- 11951659
TI  - Inactivation of human cells exposed to fractionated doses of low energy protons:
      relationship between cell sensitivity and recovery efficiency.
AB  - Within the framework of radiation biophysics research in the hadrontherapy field,
      split-dose studies have been performed on four human cell lines with different
      radiation sensitivity (SCC25, HF19, H184B5 F5-1 M10, and SQ20B). Low energy
      protons of about 8 and 20 keV/micron LET and gamma-rays were used to study the
      relationship between the recovery ratio and the radiation quality. Each cell line
      was irradiated with two dose values corresponding to survival levels of about 5%
      and 1%. The same total dose was also delivered in two equal fractions separated
      by 1.5, 3, and 4.5 hours. A higher maximum recovery ratio was observed for
      radiosensitive cell lines as compared to radioresistant cells. The recovery
      potential after split doses was small for slow protons, compared to low-LET
      radiation. These data show that radiosensitivity may not be related to a
      deficient recovery, and suggest a possible involvement of inducible repair
      mechanisms.

PMID- 11951660
TI  - Exposure rate as a determinant of the synergistic interaction of heat combined
      with ionizing or ultraviolet radiation in cell killing.
AB  - A synergistic interaction of hyperthermia with ionizing or UV light (254 nm)
      radiation was analyzed in experiments with yeast cells. For a fixed dose rate of
      radiation, the synergism was shown to be observed only within a definite
      temperature range (40-45 degrees C), inside of which there was an optimal
      temperature to achieve the highest synergism. The effectiveness of the
      synergistic interaction was smaller for haploid cells than for diploid cells.
      Experimental data from diploid yeast cells evidenced the significance of the
      exposure rate in the synergistic interaction of heat combined with ionizing or
      ultraviolet radiation. The data show that the less is the intensity of radiation,
      the lower is the temperature that should be used to provide some definite, or
      highest, synergistic interaction with the radiation. To demonstrate the
      significance of this rule for other cellular systems, the results of other
      authors published for bacterial spores and mammalian cells are discussed.
      Calculations from these results have confirmed the revealed relationship between
      the dose rate and the exposure temperature. On this basis, it is inferred that
      synergism may take place at small intensities of harmful environmental factors
      existing in the biosphere. Hence, any assessment of the health or environmental
      risks should take into account synergistic interactions between harmful agents.

PMID- 11951661
TI  - Differential gene expression in a DNA double-strand-break repair mutant XRS-5
      defective in Ku80: analysis by cDNA microarray.
AB  - The ability of cells to rejoin DNA double-strand breaks (DSBs) usually correlates
      with their radiosensitivity. This correlation has been demonstrated in
      radiosensitive cells, including the Chinese hamster ovary mutant XRS-5. XRS-5 is
      defective in a DNA end-binding protein, Ku80, which is a component of a DNA
      dependent protein kinase complex used for joining strand breaks. However, Ku80
      deficient cells are known to be retarded in cell proliferation and growth as well
      as other yet to be identified defects. Using custom-made 600-gene cDNA microarray
      filters, we found differential gene expressions between the wild-type and XRS-5
      cells. Defective Ku80 apparently affects the expression of several repair genes,
      including topoisomerase-I and -IIA, ERCC5, MLH1, and ATM. In contrast, other DNA
      repair-associated genes, such as GADD45A, EGR1 MDM2 and p53, were not affected.
      In addition, for large numbers of growth-associated genes, such as cyclins and
      clks, the growth factors and cytokines were also affected. Down-regulated
      expression was also found in several categories of seemingly unrelated genes,
      including apoptosis, angiogenesis, kinase and signaling, phosphatase, stress
      protein, proto-oncogenes and tumor suppressors, transcription and translation
      factors. A RT-PCR analysis confirmed that the XRS-5 cells used were defective in
      Ku80 expression. The diversified groups of genes being affected could mean that
      Ku80, a multi-functional DNA-binding protein, not only affects DNA repair, but is
      also involved in transcription regulation. Our data, taken together, indicate
      that there are specific genes being modulated in Ku80- deficient cells, and that
      some of the DNA repair pathways and other biological functions are apparently
      linked, suggesting that a defect in one gene could have global effects on many
      other processes.

PMID- 11951662
TI  - Optimization technique for a Prompt Gamma-ray SPECT collimator system.
AB  - Because background radiation in an irradiation room creates a problem with the PG
      SPECT (Prompt Gamma-ray Single Photon Emission Computed Tomography) system, which
      evaluates the absorbed dose for the Boron Neutron Capture Therapy treatment,
      optimization of a collimator system was performed while taking the shielding of
      background gamma-rays into consideration. Assuming that a parallel-beam
      collimator is used, three parameters--the diameter of a hole, the length of the
      collimator, and the number of detectors (the number of holes of the collimator)-
      were selected for optimization. Because the combinations of these parameters are
      limitless, it is difficult to determine them simultaneously. Therefore, a
      statistically derived Optimization Criterion has been proposed to optimize these
      parameters. When the spatial resolution was 1 cm-FWHM (full width at half
      maximum), the optimal diameter of the collimator was 5.4 mm, the optimal length
      was 321 mm, and the optimal number of detectors was 31 x 31.

PMID- 11951663
TI  - Radioprotective effects of 2-iminothiazolidine derivatives against lethal doses
      of gamma radiation in mice.
AB  - Although thiol-containing compounds have long been known to possess
      radioprotective properties, their therapeutics utility is limited by their side
      effects at radioprotective doses. In this study, a series of 2-iminothiazolidine
      derivatives were prepared and their toxicity and radioprotective effects in NMRI
      mice were determined using the LD50/30 end point. The LD50 values, as determined
      by a Probit analysis, were between 11 and 14 mg/kg. For studying radioprotective
      effects, one-sixth of the toxic LD50 values were used, namely 2 and 2.2 mg/kg. To
      evaluate the radioprotective capabilities, mice were exposed to lethal doses of
      cobalt-60 gamma-radiation alone or in the presence of compounds. The percentage
      survival of mice at 30 days for these compounds compared to control mice were 10
      to 30% when injected 15 and 30 minutes before gamma-irradiation. They were
      significant compared to the control group (P < 0.05). 2-Imino-3
      (benzoylmethyl)thiazolidine derivatives showed different radioprotective effects
      when injected at different times before irradiation, but were not statistically
      significant from each other (P > 0.05).

PMID- 11951665
TI  - Womb to world: a metabolic perspective.

PMID- 11951664
TI  - Increased base change mutations at G:C pairs in Escherichia coli deficient in
      endonuclease III and VIII.
AB  - Various types of mutation induced by oxidative DNA damage, induced by hydrogen
      peroxide and riboflavin photosensitization, were determined in Escherichia coli
      (E. coli) mutants deficient in endonuclease III (endo III) and endonuclease VIII
      (endo VIII). The majority of hydrogen peroxide-induced and spontaneous mutations
      consisted of G:C to A:T and to T:A base changes, shown on the mutation assay
      system by a reversion at a specific site of the lacZ gene. Base changes were also
      localized at G:C pairs in the mutation of the supF gene, induced by riboflavin
      photosensitization, which specifically yields 7,8-dihydro-8-oxoguanine (8-oxoG).
      G:C to T:A and to C:G transversions dominated in both mutants. These results
      suggest that endo III and endo VIII are involved in the repair of oxidative
      lesions of guanine.

PMID- 11951666
TI  - What midwives need to know about postpartum depression.

PMID- 11951667
TI  - Sacred ground.

PMID- 11951668
TI  - How I overcame postpartum depression.

PMID- 11951670
TI  - Postpartum care from ancient India.

PMID- 11951669
TI  - Baby's bedding: is it creating toxic nerve gases?

PMID- 11951671
TI  - Having a healthy, happy postpartum. How midwifery today's newest "baby" can help
      you.

PMID- 11951672
TI  - The fourth trimester.

PMID- 11951673
TI  - Are you a size-friendly midwife?

PMID- 11951674
TI  - Birth of a midwife.

PMID- 11951675
TI  - Challenging births 3.

PMID- 11951676
TI  - Postpartum: rebirth of the woman.

PMID- 11951677
TI  - How to make a portable waterbirth tub.

PMID- 11951678
TI  - Shiatsu: another tool for keeping birth normal.

PMID- 11951679
TI  - Keeping the faith.

PMID- 11951680
TI  - Birth, love and death.

PMID- 11951681
TI  - Loss and the midwifery community.

PMID- 11951682
TI  - How do you feel about giving up your freedom?

PMID- 11951683
TI  - Cuban maternity homes.

PMID- 11951684
TI  - Peru: midwifery on high.

PMID- 11951685
TI  - Birth in India: one chosen perspective.

PMID- 11951686
TI  - The Dutch model: postpartum care in The Netherlands.

PMID- 11951687
TI  - From the United Kingdom.

PMID- 11951688
TI  - What are the essential elements of good postpartum care?

PMID- 11951689
TI  - The first hour following birth: don't wake the mother!

PMID- 11951690
TI  - "World-class service": patient satisfaction in a customer-driven market.

PMID- 11951691
TI  - Len Berry on Mayo's "soul of service".

PMID- 11951692
TI  - 10 strategies for becoming "best-of-breed" service providers.

PMID- 11951693
TI  - Integrated diagnostic approach to suspected deep vein thrombosis and pulmonary
      embolism.
AB  - Diagnosing deep vein thrombosis and pulmonary embolism has become definitely
      easier and more reliable over the past fifteen years, especially thanks the
      development of lower limbs venous compression ultrasonography and fibrin D-Dimer
      measurement. These tests allowed reducing the requirement for venography and
      pulmonary angiography to a small minority of patients. Simultaneously,
      ventilation/perfusion lung scan criteria have been standardized, and the
      performance of spiral computed tomography has been analyzed in an appropriate
      way. New sequential, mainly noninvasive strategies could be developed that proved
      to be safe in large-scale prospective cohort studies with prolonged follow-up.
      They should now be implemented in daily practice according to cost-effectiveness
      analyses as well as local facilities and expertise.

PMID- 11951694
TI  - Indications for and limitations of exercise training in patients with
      intermittent claudication.
AB  - BACKGROUND: The selection of candidates for exercise training among patients with
      intermittent claudication is still a matter of debate. PATIENTS AND METHODS:
      Forty-nine patients with intermittent claudication due to arteriosclerosis
      obliterans were tested. Forty-six patients were men and 3 were women, with an
      average age of 65 years (range, 46 to 76 years). The patients walked on a
      treadmill at 2.4 km/h on a 12% upgrade followed by an appropriate period of rest
      for 30 minutes twice a day during a 3-week hospitalization. Programs were
      individualized for each patient. Four parameters were assessed after exercise
      training: (1) Ankle-brachial index (ABI) at rest, (2) Fall in ABI after 40 m of
      treadmill walking (ABI Fall 40), (3) the recovery time (RT 40) required for the
      ABI to return to resting levels after 40 m of walking, and (4) the maximal
      walking distance (MWD) on the treadmill. RESULTS: The average ABI at rest before
      the 3-week training period was 0.60 +/- 0.02 (mean +/- SE), and after training it
      was 0.62 +/- 0.02. There was a small although not statistically significant
      increase in the ABI after training. This increase in the ABI did not exceed 0.21.
      The average ABI Fall 40 before training was 0.36 +/- 0.01, and after training it
      was 0.30 +/- 0.02. The average RT 40 before training was 9.9 +/- 0.8 min, and
      after training it was 6.2 +/- 0.6 min. There were significant decreases in the
      ABI Fall 40 and RT 40 after training (p < 0.01 and p < 0.001, respectively). The
      MWD increased after training in 48 of the 49 patients. The average MWD increased
      from 134 +/- 13 m to 226 +/- 32 m after training (p < 0.001). The occlusion
      levels did not influence the results as training effects and hemodynamic
      parameters. Fourteen of 49 patients desired arterial reconstruction after
      exercise training. CONCLUSIONS: Patients with shorter RT 40's before training
      achieved greater increases in the MWD after training. In patients with an RT 40
      under 12 min, exercise training is indicated. However, there is some discrepancy
      between the increase in MWD and the degree of satisfaction in individual
      patients.

PMID- 11951695
TI  - Effects of exercise training program on functional capacity and quality of life
      in patients with peripheral arterial occlusive disease. Evaluation of a pilot
      project.
AB  - BACKGROUND: In patients with peripheral arterial occlusive disease (PAOD) stage
      II, exercise training seems to be important to reduce symptoms and improve
      functional capacity. We evaluated the effects of an out-patient treatment program
      on walking distance (standardized treadmill testing), training exercise capacity,
      and disease specific quality of life (PAVK-86 questionnaire). METHODS AND
      RESULTS: Thirty-one patients aged 70 +/- 2 with intermittent claudicatio in stage
      IIa/IIb according to Fontaine (n = 18/13) underwent a supervised 12 week exercise
      training and education outpatient program. During course of intervention,
      patients demonstrated improvements in pain-free training walking distance (p <
      0.001) and repetitions of tiptoe standing (p < 0.05). In standardized treadmill
      testing, pain-free walking distance was improved by 182% (129 +/- 19 m-->364 +/-
      53 m; p < 0.001), and maximum walking distance by 76% (311 +/- 42 m-->546 +/- 63
      m; p < 0.01). Before training, mean subscale scores of the PAVK-86 demonstrated
      distinct impairments concerning pain and functional status. After 12 weeks of
      intervention, with exception of the subscale complaints, all dimensions of
      quality of life assessed have improved significantly. The highest effect size was
      observed for the subscales pain, mood, and functional status. Improvement in the
      subscale anxiety and pain-free walking distance (treadmill test) correlated
      significantly (r = 0.46) as well as improvement in the subscale mood and maximum
      walking distance (r = 0.45). CONCLUSION: In patients with PAOD stage II
      considerable effects on functional capacity and important dimensions of quality
      of life can be achieved by a short exercise and education program.

PMID- 11951696
TI  - [Blind segments of memory].

PMID- 11951697
TI  - Clinical long-term results of percutaneous transluminal angioplasty in patients
      with peripheral arterial occlusive disease.
AB  - BACKGROUND: We investigated the long-term clinical results of percutaneous
      transluminal angioplasty (PTA) in patients with peripheral arterial occlusive
      disease (PAOD) and the influence of different parameters on the primary success
      rate, the rate of complications and the long-term outcome. PATIENTS AND METHODS:
      We reviewed clinical and hemodynamic follow-up data of 166 consecutive patients
      treated with PTA in 1987 in our department. RESULTS: PTA improved the clinical
      situation in 79.4% of patients with iliac lesions and in 88.3% of patients with
      femoro-popliteal lesions. The clinical stage and ankle brachial index (ABI) post
      interventional could be improved significantly (each P < 0.001), the same results
      were observed at the end of follow-up (each P < 0.001). Major complications
      occurred in 11 patients (6.6%). The rate of primary clinical long-term success
      for suprainguinal lesions was 55% and 38% after 5 and 10 years (femoro-popliteal
      44% and 33%), respectively, the corresponding data for secondary clinical long
      term success were 63% and 56% (60% and 55%). Older age (P = 0.017) and lower ABI
      pre-interventional (P = 0.019) significantly deteriorated primary clinical long
      term success for suprainguinal lesions, while no factor could be identified
      influencing the outcome of femoro-popliteal lesions significantly. CONCLUSION:
      Besides an acceptable success rate with a low rate of severe complications, our
      results demonstrate favourable long-term clinical results of PTA in patients with
      PAOD.

PMID- 11951698
TI  - Prospective study of 36 patients with 46 popliteal artery aneurysms with non
      surgical treatment.
AB  - BACKGROUND: There is a lack of prospective studies with popliteal aneurysms (PAA)
      < 2 cm and the very few information about the natural cause of the disease.
      PATIENTS AND METHODS: Between 1995 and 2000 46 patients having 65 popliteal
      artery aneurysms have been examined. The mean diameter was 1.9 cm (0.8-4 cm). In
      41% of the cases PAA were bilateral, additional extrapopliteal aneurysms were
      found in 37%. The PAA was occluded in 8 patients at the initial examination (mean
      diameter 2.4 cm: 1.4-4 cm). One of these patients had to be amputated (long-term
      diabetes, dialysis and severe generalized peripheral arteriosclerosis). Since no
      information could be obtained from two patients, it was possible to prospectively
      monitor 36 patients with 46 PAA (30 m, 6 f) over a period of 2.5 years. 19
      patients were treated with platelet inhibitors, 16 with coumarin and one refused
      any thromboembolic prophylaxis. The patients were examined every year by
      telephone interview and duplexsonography. RESULTS: During the monitoring period
      there occurred two complete occlusions and one distal arterial progression, while
      2 patients died, but no amputation. The total complication rate was 6.5% with a
      higher incidence in PAA > 2 cm of diameter (14.2 vs. 3.1%). All complications
      were found in PAA with mural thromboses. Coumarin seems to be superior platelet
      aggregation inhibitors with a complication rate of 0% vs. 14.3%. The mean
      increase in diameter during follow-up was dependent on PAA size, 1.5 mm/year for
      PAA > 2 cm vs. 0.7 mm/year for PAA < 2 cm. CONCLUSION: This prospective study
      emphasises the necessity of a prophylactical surgery in patients with an aneurysm
      diameter > 2 cm. In view of the low rate of complications of the natural course
      of PAA (6.5% of all PAA or 14.2% for PAA > 2 cm/2.5 years), the bypass surgery
      should be performed by an experienced vascular department. Patients with PAA < 2
      cm or patients with contraindication for peripheral bypass should receive
      anticoagulation.

PMID- 11951699
TI  - Surgical management of prosthetic vascular graft infection: comparative
      retrospective analysis of 30 consecutive cases.
AB  - BACKGROUND: Graft infection after vascular prosthetic reconstruction for the
      treatment of peripheral arterial occlusive disease (PAOD) is a rare but severe
      complication with poor outcome. The options for surgical treatment are not
      uniformly accepted and remain controversial. PATIENTS AND METHODS: We
      retrospectively analyzed the histories of 30 patients treated for prosthetic
      graft infection (Szilagyi grade III) in our hospital between 1994 and 1999 to
      determine which forms of treatment were best suited for which types of patient.
      In the majority of cases the initial treatment was lower-extremity bypass
      surgery. The most frequent location of infection was the groin (73%).
      Staphylococci (13% of which were methicillin resistant) were the most common type
      of bacteria. The overall incidence of prosthetic infection was 2.3%. RESULTS:
      After confirmation of the infection by computed tomography (CT) or white blood
      cell scintigraphy, one of the following 5 forms of surgical treatment was
      performed: 1. Removal of the infected prosthesis and its simultaneous replacement
      by an autologous vein bypass. 2. Bypass removal and secondary replacement by an
      autologous vein. 3. Extra-anatomical replacement. 4. Graft removal and primary
      amputation. 5. Local therapy with debridement and secondary wound healing. In
      some patients primary amputation after graft infection was necessary to prevent
      further deterioration with fulminant sepsis. The overall mortality was 17%, the
      amputation rate was 60%. CONCLUSIONS: The best results were achieved by early
      complete removal of the alloplastic material and one-step replacement by either
      an autologous vein or extra-anatomic bypass. This resulted in a limb salvage rate
      of 54% and 40% and mortality rates of 9% and 0%, respectively.

PMID- 11951700
TI  - [Acute ischemia of the leg in a drug addict].
AB  - A 39 year old male comes to the emergency room because of rapidly increasing pain
      in his left leg one hour after the injection of Flunitrazepam into a groin
      vessel. There is a history of drug abuse for more than 15 years. The left leg is
      cool and shows intense patchy cyanosis. The same skin discoloration is seen at
      the left lower abdomen and parts of the thigh. The leg is paretic but foot-pulses
      are detectable. Color-coded duplex-sonography of the left leg shows normal shaped
      arteries with regular flow. Regarding the veins there are post-thrombotic changes
      but no signs of actual thrombosis. The ECG shows sinus rythme. No source of
      emboli can be found by echocardiography. The laboratory tests reveal normal
      results except of anemia (Hb 9.6 g/dl, normocytic, normochromic). As an
      accidental intraarterial injection with a toxic/allergic insult to the vessel
      walls has to be supposed the patient is treated besides of analgesics with
      systemic anticoagulation, high doses of cortisone and calcium channel-blockers.
      With this therapeutic regimen the leg and the left lower abdomen improve
      gradually except for some toes which remain cyanotic. During the first days the
      patient develops signs of moderate rhabdomyolysis with swelling of the leg and an
      increase of creatininase concentration in blood. After 12 days the left leg has
      normalised but the toes show further demarcation. They have to be amputated six
      weeks later. The accidental injection of drugs into the femoral artery may result
      in the clinical picture of acute limb ischemia without occlusion of the big
      vessels of the leg. This obviously occurs most often with benzodiazepines,
      especially when crushed tablets soluted in water are injected. Color-coded duplex
      sonography is able to show open vessels within minutes and prevents ineffective
      surgical interventions.

PMID- 11951701
TI  - Fulminate intracardiac thrombosis associated with Budd-Chiari-syndrome and
      inferior vena cava thrombosis.
AB  - The most common cause of edema of the legs and dyspnea is congestive heart
      failure. Further differential diagnosis such as renal or hepatic failure have to
      be considered. We report the case of a previous healthy 65-year-old woman who
      developed dyspnea and massive edema of the legs followed by acute hepatic and
      renal failure. Imaging studies showed a thrombosis of the inferior vena cava
      (IVC) caused by a tumor between the right kidney and the IVC. Histological
      examination revealed a leiomyosarcoma of the IVC. Hepatic failure due to venous
      outflow obstruction (Budd-Chiari syndrome, BCS) was diagnosed. Coagulation
      profile showed a complex disorder due to acute hepatic failure. Factor V Leiden
      and prothrombin gene mutation G20210A could be excluded. The thrombosis extended
      from the femoral veins up to the right atrium. After 11 days of anticoagulation
      with heparin platelet counts decreased by more than 50%. Suspecting a heparin
      induced thrombocytopenia the patient was placed on recombinant hirudin
      (lepirudin) for anticoagulation. Hepatic venogram showed a thrombosis of the
      hepatic vein orifices but not of the hepatic veins. The tumor and the thrombi
      were removed surgically. When the cardiopulmonary bypass was terminated new
      intracardiac thrombi occurred. Despite immediate surgical intervention the
      patient finally died due to right ventricular failure caused by the fulminate
      intracardiac thrombosis. In conclusion, thrombosis of the IVC may mimic
      congestive heart failure and may cause BCS. Neoplasms and coagulation disorders
      may cause thrombosis of the IVC.

PMID- 11951702
TI  - Traveller's thrombosis 2001.

PMID- 11951703
TI  - Air travel thrombosis 2001.

PMID- 11951705
TI  - Open letter for ISIAQ readers.

PMID- 11951704
TI  - Color coded duplex sonography of inguinal vessels in i.v. drug addicts.
AB  - BACKGROUND: During recent years increasing numbers of intravenous drug addicts
      with severe damage to the groin vessels were examined in our angiological
      ultrasound laboratory. The value of color duplex sonography for the clinical
      evaluation of these findings is the subject of the present study. PATIENTS AND
      METHODS: Over the course of six years every drug addict admitted to our hospital
      who either complained of pain or discomfort in the inguinal region or showed
      conspicuous clinical findings in this area was examined in our ultrasound
      laboratory. First by B-mode, the diameter, wall structure and compressibility of
      the vessels were evaluated and the surrounding tissue was checked for
      abnormalities. Then the blood flow of the femoral vessels was examined by color
      coded duplex. If an abscess was suspected, a computed tomography of the groin was
      obtained before surgery in most cases. RESULTS: A total number of 77 patients was
      examined with pathologic results in all cases. The most frequent finding was
      venous thrombosis: In 63 patients complete thrombotic occlusion of the femoral
      vein at the injection site was observed. We registered 14 partial thromboses. 30
      patients showed vessel wall alterations to variable extents in which 23 cases
      referred to veins and 10 cases to arteries. 7 patients showed an occlusion of the
      femoral artery. In 4 patients we found a false aneurysm and 3 had an
      arteriovenous fistula. Chronic tissue alterations were present to a certain
      extent in all cases rendering evaluation frequently difficult. Especially
      problematic to evaluation were those 34 patients where one or more surgical
      interventions had been performed previously. The results of an additional
      computed tomography had little effect on the therapeutic decisions. In 11
      patients an abscess incision had to be done during the course of their hospital
      stay. CONCLUSION: Extensive damage of the groin vessels is seen in i.v. drug
      addicts. There is no other patient group with such a diversity of different
      findings. In almost every case these findings involve veins and arteries as well
      as the surrounding tissues.

PMID- 11951706
TI  - Characterization and reduction of formaldehyde emissions from a low-VOC latex
      paint.
AB  - The patterns of formaldehyde emission from a low volatile organic compound (VOC)
      latex paint applied to gypsum board were measured and analyzed by small
      environmental chamber tests. It was found that the formaldehyde emissions
      resulted in a sharp increase of chamber air formaldehyde concentration to a peak
      followed by transition to a long-term slow decay. A semi-empirical first-order
      decay in-series model was developed to interpret the chamber data. The model
      characterized the formaldehyde emissions from the paint in three stages: an
      initial "puff" of instant release, a fast decay, and a final stage of slow decay
      controlled by a solid-phase diffusion process that can last for more than a
      month. The model was also used to estimate the peak concentration and the amount
      of formaldehyde emitted during each stage. The formaldehyde sources were
      investigated by comparing emission patterns and modeling outcomes of different
      paint formulations. The biocide used to preserve the paint was found to be a
      major source of the formaldehyde. Chamber test results demonstrated that
      replacing the preservative with a different biocide for the particular paint
      tested resulted in an approximate reduction of 55% of formaldehyde emissions. But
      the reduction affected only the third-stage long-term emissions.

PMID- 11951707
TI  - Gas/particle partitioning and size distribution of primary and secondary
      carbonaceous aerosols in public buildings.
AB  - The gas and particulate phase of semi-volatile organic compounds (six samples)
      and the composition of organic aerosol as a function of particle size (six
      samples) were studied in two public buildings in Greece. The objectives of this
      study were: i) to chemically characterize the organic content of indoor gas and
      particulate phases; ii) to classify indoor organic aerosol constituents as a
      function of particle size; and iii) to reconcile the sources of organic compounds
      indoors. Non-polar, semi-polar, polar, and acidic compounds were identified in
      both gas and particulate phases by using gas chromatography/mass spectrometry
      (GC/MS). Branched iso- and anteiso-alkanes were used to trace environmental
      tobacco smoke (ETS) concurrently with other compounds. Polycyclic aromatic
      hydrocarbons (PAHs) in the gas phase gave a pattern more characteristic to ETS
      than the corresponding pattern in the particulate phase. The chemical composition
      observed for n-alkanols and n-alkanoic acids in both gas and particulate phases
      indicated ETS as one of their main sources indoors. PAHs and n-alkanols were
      evenly associated between fine and coarse particles and their corresponding total
      mean mass median aerodynamic diameter (MMAD) was 1.27 and 1.38 microns
      respectively, indicating a mixed origin. Conversely, the MMAD of n-alkanes,
      unresolved complex mixture (UCM), iso- and anteiso-alkanes and free fatty acids
      varied from 0.30 to 0.62 micron denoting a stronger association with indoor
      sources.

PMID- 11951708
TI  - Predictors of high endotoxin concentrations in the settled dust of German homes.
AB  - Endotoxin concentrations in settled house dust were measured within the
      collaborative study named INGA (Indoor Exposure and Genetics in Asthma) together
      with other asthma-related indoor factors in 405 randomly selected homes in two
      German cities. Endotoxin was assayed using the quantitative kinetic chromogenic
      Limulus Amebocyte Lysate (LAL) method. The mean concentration of 2,274 ng
      endotoxin/g dust in living rooms is about two orders of magnitude below mean
      occupational exposure (e.g. agriculture). Endotoxin concentrations are higher in
      old buildings (means ratio = (MR) 1.52, 95% C.I.: 1.14; 2.04), and in the lower
      storey of the dwelling (MR = 1.30, 95% C.I.: 1.04; 1.62). Furthermore, higher
      endotoxin concentrations are associated with longer occupancy in the apartment
      (MR = 1.63, 95% C.I.: 1.21; 2.18), high utilisation of the apartment during the
      sampling period (MR = 2.52, 95% C.I.: 1.42; 4.47), infrequent vacuum cleaning of
      the carpets (MR = 1.67; 95% C.I.: 1.10; 2.54), an indifferent attitude to
      ventilation (MR = 1.37; 95% C.I.: 1.03; 1.82), keeping cats (MR = 1.91; 95% C.I.:
      1.43; 2.55) and dogs (1.57; 95% C.I.: 1.08; 2.30), as well as the occurrence of
      mice (MR = 1.39; 95% C.I.: 1.00; 1.93). The season and indoor climate (operative
      temperature and relative humidity) did not effect endotoxin concentration. These
      results indicate that high endotoxin concentration in settled dust is an
      indicator of poor hygienic conditions in homes.

PMID- 11951709
TI  - Psychosocial dimensions of solving an indoor air problem.
AB  - This investigation focuses on the psychological and social dimensions of managing
      and solving indoor air problems. The data were collected in nine workplaces by
      interviews (n = 85) and questionnaires (n = 375). Indoor air problems in office
      environments have traditionally utilized industrial hygiene or technical
      expertise. However, indoor air problems at workplaces are often more complex
      issues to solve. Technical questions are inter-related with the dynamics of the
      work community, and the cooperation and interaction skills of the parties
      involved in the solving process are also put to the test. In the present study,
      the interviewees were very critical of the process of solving the indoor air
      problem. The responsibility for coordinating the problem-managing process was
      generally considered vague, as were the roles and functions of the various
      parties. Communication problems occurred and rumors about the indoor air problem
      circulated widely. Conflicts were common, complicating the process in several
      ways. The research focused on examining different ways of managing and resolving
      an indoor air problem. In addition, reference material on the causal factors of
      the indoor air problem was also acquired. The study supported the hypothesis that
      psychosocial factors play a significant role in indoor air problems.

PMID- 11951710
TI  - The field comparison of three measuring techniques for evaluation of the surface
      dust level in ventilation ducts.
AB  - This paper reports the comparison of three measuring methods for quantifying the
      amount of dust on the inner surface of ventilation ducts: 1) a vacuum test
      method; 2) a gravimetric tape method; and 3) an optical method. Thirteen recently
      constructed buildings were selected for the field test in the Helsinki
      metropolitan area. The dust samples in each method were all taken from the same
      location in the duct. Most of the ducts sampled had no residual oil originating
      from the manufacturing process. The mean amount of dust measured with the vacuum
      test method was 1.3 g/m2 and the range was < 0.1-8.4 g/m2. The mean surface dust
      level measured using the gravimetric tape method was slightly lower, i.e. 1.2
      g/m2 (< 0.1-5.0 g/m2). The mean cleanliness level of the ducts was 15% (2-41%)
      using the optical method. The wide variations and differences in the results of
      the different methods were caused by the unequal distribution of dust on the duct
      surfaces.

PMID- 11951711
TI  - Volatile organic pollutants in new and established buildings in Melbourne,
      Australia.
AB  - Volatile organic compounds (VOCs) within new and established buildings have been
      determined and factors significant to their presence have been identified. In
      established dwellings, total volatile organic compound (TVOC) concentrations were
      low, but were approximately four times higher than in outdoor air, showing a
      dominant effect of indoor sources. The presence of attached garages, site
      contamination and 'faulty' wool carpet were associated with higher indoor
      pollution. In three dwellings, unidentified sources of benzene were indicated.
      Much higher VOC concentrations were observed in new or renovated buildings,
      persisting above "baseline" levels for several weeks, concentration decay rate
      correlating with VOC molecular volume, indicating emissions were limited by
      material diffusion processes. VOC and formaldehyde emission decays in a new
      dwelling occurred by a double-exponential source model. This shows that
      persistent low levels of volatile organic pollutants in established dwellings can
      occur due to long-term emissions from building materials.

PMID- 11951712
TI  - Dispersion of particles from vehicle emissions around high- and low-rise
      buildings.
AB  - Understanding the distribution of outdoor pollutants around a building envelope,
      generated by sources located in its vicinity, is important when choosing the
      location of building ventilation system intakes, as well as for quantifying the
      exposure of people living or working in the building. A systematic experimental
      characterisation of the number concentration of submicrometre particles was
      undertaken around the envelope of six buildings (both low- and high-rise) at
      different distances from a road (the main pollution source). The concentrations
      were measured using two TSI Scanning Mobility Particle Sizers. PM2.5
      concentrations were also monitored around the low-rise buildings using two TSI
      DustTraks. For the three high rise buildings the concentration of fine and ultra
      fine particles decreased in most cases to about 50-60% from the approximate
      ground level readings (between heights of 0 to 6 m), to full building height
      (from 24 to 33 m above the ground). Measurements of submicrometre particle number
      concentrations as well as PM2.5 fraction in the envelope around low-rise isolated
      buildings did not show any significant trends from the front to the rear of the
      building. The sensitivity of PM2.5 measurements to a small number of larger
      particles, possibly from sources other than vehicle emissions, was observed.

PMID- 11951713
TI  - Measuring depression in Korean Americans: development of the Kim Depression Scale
      for Korean Americans.
AB  - This article discusses issues related to measuring depression in linguistic and
      cultural minority groups, using Korean Americans as an example. The article
      details the process of developing and evaluating a depression-screening tool for
      Korean Americans. A series of focus groups was conducted in the development stage
      of the study. In the evaluation phase, 154 first-generation Korean Americans
      participated in the assessment of the psychometric properties of the newly
      developed depression scale, the Kim Depression Scale for Korean Americans
      (KDSKA). The KDSKA showed adequate reliability, validity, and potentially high
      sensitivity as a depression-screening tool for Korean Americans.

PMID- 11951714
TI  - Students' knowledge, attitudes, and beliefs about AIDS: a cross-cultural study.
AB  - This exploratory, comparative study was conducted to assess and compare the
      knowledge, attitudes, and beliefs toward AIDS between a group of Jordanian and a
      group of American students. A convenience sample consisting of 126 senior BSN
      (bachelor's of nursing) students, 63 from a university in Jordan and 63 from a
      university in Michigan, was selected for this study. A self-administered
      structured questionnaire was utilized. The questionnaire consisted of three
      parts: knowledge, attitudes, and beliefs toward AIDS in both cultures.
      Descriptive and inferential statistical analyses were used. The results indicated
      that the American students' responses concerning knowledge of HIV/AIDS were
      significantly greater (M = 73%) in comparison with Jordanian students' (M = 52%).
      The American students also reported more positive attitudes toward AIDS than
      those of their Jordanian counterparts. In terms of prevention of the spread of
      HIV/AIDS, more American students (82.5%) approved of the use of condoms as a
      precautionary measure toward the spread of the disease when compared to Jordanian
      students.

PMID- 11951715
TI  - Hmong health beliefs and experiences in the western health care system.
AB  - This ethnographic study was conducted to determine Hmong perspectives and beliefs
      that influence the Hmong experience in Western medical situations. Hmong
      perspectives regarding the body as well as descriptions of Hmong experiences
      within the American medical system were explored using participant observation
      and interviews over a 2-year time frame. Two focus groups were conducted to
      confirm findings. Data indicates that the Hmong language lacks terms that
      translate biomedical body physiology and anatomy. Medical terms and diagnoses
      lack direct translation and require extensive nondirect terms to approximate
      meaning. Differences between Hmong traditional beliefs and Western biomedical
      beliefs create a lack of understanding. Negative health care experiences result
      in Hmong community members' mistrust and fear of Western medicine.

PMID- 11951716
TI  - Culturally sensitive caring for Saudi patients.
AB  - The Saudi Arabian health system is mainly staffed by non-Saudi health
      professionals recruited from all over the world. At times, inadequate cultural
      awareness by health professionals can render their caring for Saudi patients more
      challenging than joyful. It is possible, however, that this equation can be
      easily reversed should the Saudi culture be introduced to health professionals
      planning to care for Saudis. In this article, a Saudi health professional
      describes some of the pertinent cultural aspects that could help non-Saudi health
      professionals improve their awareness about Saudi culture. The religion of Islam
      is the main, though not the only, factor that shapes the Saudi culture. This
      article, therefore, could also interest those caring for Arab and Muslim patients
      worldwide.

PMID- 11951717
TI  - Assessing cultural competence of policy organizations.
AB  - Assessment of the capabilities of human service providers to care for individuals
      from diverse cultures has been widely discussed in the literature. However, a
      less examined area is the appraisal of the cultural competence of the
      administrative or policy bodies whose actions shape the character of these human
      services. This article demonstrates an approach for evaluating a policy
      organization's cultural competence using a governmental agency as a case study.
      Findings from this assessment prompted this agency to generate plans to further
      enhance its cultural competence.

PMID- 11951718
TI  - Embracing street culture: fitting health care into the lives of street youth.
AB  - The purpose of this article is to describe a unique model for the provision of
      comprehensive primary health care for homeless youth in Seattle, Washington.
      Through the description of our program, we argue for the use of youth-centric
      instead of youth-friendly programs. This means a change from using the friendly
      health program as the central focus to having the young people be the starting
      point and adapting the health service to meet their needs. We describe how our
      model of care optimizes chances for homeless youth to establish positive
      connections with caring adults. We also show how homeless youth have their own
      street culture, which is of primary importance to them and which has a powerful
      impact on how they use and view health care.

PMID- 11951719
TI  - Foreign nurse recruitment and workforce diversity.

PMID- 11951720
TI  - Qualitative health research in Ibero-America: the current state of the science.
AB  - Qualitative health research (QHR) comprises a field that has spread and
      consolidated in Ibero-America (Iberian and Latin American countries) during the
      1990s. Until now, however, no systematic evaluation has been made of the
      qualitative health research published in the region. The aim of this article is
      to discuss four aspects of QHR: the capability and limitations of using
      international databases to identify Ibero-American qualitative health studies;
      the principle health topics studied in Latin America using QHR methodologies; the
      development of QHR in Spain; and the theoretical perspectives that guide studies
      in Latin America. A bibliographic search was conducted to identify QHR studies
      listed in 17 international and/or regional databases. A parallel search was
      conducted by contacting research centers, academic institutes, and key
      researchers in several countries.

PMID- 11951721
TI  - Hospital slashes pneumonia rate with quality project for early intervention.

PMID- 11951722
TI  - What you need to know before hiring a surveyor.

PMID- 11951723
TI  - Discharge process enables faster placement.

PMID- 11951724
TI  - To smooth discharge, check bed 'life cycle'.

PMID- 11951725
TI  - Teleconferences help educate on bioterrorism.

PMID- 11951726
TI  - Patient safety alert. Early results of Leapfrog hospital survey promising.

PMID- 11951727
TI  - Bioterrorism watch. Building a bridge over the abyss: will bioterrorism help
      bring disjointed health system together?

PMID- 11951728
TI  - Patient safety alert. Safety tool stresses education and action.

PMID- 11951729
TI  - Bioterrorism watch. Was anthrax mailer a bioweapons researcher?

PMID- 11951730
TI  - The ongoing growth of defined contribution and individual account plans: issues
      and implications.
AB  - This Issue Brief discusses the implications of the growth of defined contribution
      (DC) retirement plans and individual account plans and the subsequent impact on
      employers, employees, and retirement planning. It also presents a look at data
      regarding contributions to retirement plans, employer trends regarding retirement
      plans, and the potential impact of changes to the federal Social Security
      retirement system. The findings and data in this article are drawn from material
      presented at a policy forum sponsored by the Employee Benefit Research Institute
      Education and Research Fund (EBRI-ERF) Dec. 7, 2001, in Washington, DC. Today,
      prospective retirees need to be able to generate about 75 percent of their
      current income to maintain their standard of living in retirement, up from 63
      percent of their income in 1997, according to the Replacement Ratio Study, by Aon
      Corporation and Georgia State University. However, the most recent data show a
      decline in the percentage of income that average employees are saving. While it
      is too early to quantify, it does not appear that the retirement provisions in
      the Economic Growth and Tax Relief Reconciliation Act of 2001 (EGTRRA) are
      strongly influencing the movement to DC plans. However, employers appear very
      interested in the provisions of the new law with regard to both defined benefit
      (DB) retirement plans and DC plans. The number of large employers offering DB
      plans continues to decline, from 85 percent in 1990 to 73 percent in 2000,
      according to the Hewitt study. Although employers may have little influence over
      some factors that affect participation rates in voluntary retirement plans, they
      have various options to increase participation rates, such as "matching" employee
      contributions, offering loan features, and providing education to employees about
      the plans.

PMID- 11951732
TI  - Eat more onions.

PMID- 11951731
TI  - New drugs for osteoarthritis and infections caused by gram-positive bacteria.

PMID- 11951733
TI  - HIV fights back.

PMID- 11951734
TI  - Diabetes: a Cuban-American perspective.

PMID- 11951735
TI  - Pediatric assessment in the home.
AB  - Caring for children holistically in the home can be challenging and is dependent
      on working closely with families. This article identifies the four roles a nurse
      performs when conducting a home pediatric assessment. The Home Risk Assessment
      Tools presented assist nurses in evaluating a child's physical and psychosocial
      needs.

PMID- 11951736
TI  - What's new in pain management?

PMID- 11951737
TI  - When your patient is enrolled in a research study.
AB  - Framed in a research context, this article gives you some insight into your roles
      and responsibilities as an advocate for patient's rights, a support person, and a
      healthcare monitor. Ethical principles guiding research and implications for
      practice are discussed.

PMID- 11951738
TI  - Computer and Internet use by home care and hospice agencies.
AB  - Nurses in home healthcare and hospice are embracing the advances in computer
      science and technology to provide an edge in administration and clinical
      practice. Of concern to nurse managers is the extent to which personal computers
      and the Internet have been used in home healthcare and hospice, and what
      information, opportunities, and needs related to education are on the horizon.
      This article discusses the results of a national survey conducted exclusively on
      the World Wide Web to answer these questions.

PMID- 11951739
TI  - Chemotherapy-related anemia and fatigue in home care patients. A home care
      nurse's guide to recognition, assessment, and intervention.
AB  - This supplement provides an overview of chemotherapy-related anemia and fatigue
      in oncology patients. It outlines how home care nurses can recognize and assess
      fatigue, understand its causes, and provide the patient with treatment options.
      Strategies and tools that aid nurses in assessment and treatment are also
      provided.

PMID- 11951740
TI  - Needlestick legislation: a sharp idea.

PMID- 11951741
TI  - Is obesity overplayed in the older adult?

PMID- 11951742
TI  - Normative treatment guidelines in home care: building the case.
AB  - To effectively market programs and maximize resources under a prospective payment
      system, home healthcare agencies need to look closely at standardizing treatment
      practices to link patient outcomes to the care provided. This article discusses
      the issues, methods, and processes used to test treatment guidelines and
      strategies to improve existing guidelines through evidence-based research.

PMID- 11951743
TI  - Using behavior modification to promote wound healing.
AB  - Successfully caring for patients with wounds under PPS demands that current
      practice approaches must change. Instead of focusing on dressings and techniques
      alone, this article describes how first addressing patients' psychological
      readiness for change can move them quickly to self-care and enhance wound
      healing, which results in cost savings and better outcomes.

PMID- 11951744
TI  - Is the cost of home care greater than the cost of nonadherence? Catrina's journey
      through the maze of HIV medications and managed care.
AB  - This article describes the case study of Catrina, a 37-year-old African-American
      woman with AIDS. Because of managed care visit limitations, Catrina had four
      admissions to and three discharges from home care services surrounding three
      different regimens of highly active antiretroviral therapy. By highlighting the
      toll that the maze of managed care has had on her life, the authors raise issues
      regarding the inadequacy of home care reimbursement. The Motown and other musical
      headings in this article are dedicated to Catrina.

PMID- 11951745
TI  - It's a shame.

PMID- 11951746
TI  - Violence and home care. A focus group study.
AB  - This study describes home caregivers' and managers' beliefs and experiences
      related to violence in their workplace. Suggested strategies are recommended that
      can help home care organizations recognize, prevent, and manage violence in their
      workplace.

PMID- 11951747
TI  - Your patient may be at risk for isolated systolic hypertension!
AB  - Isolated systolic hypertension is a risk factor for the development of stroke,
      heart attack, and left ventricular hypertrophy, which can result in eventual
      congestive heart failure. Recent studies have validated the benefits of treatment
      of isolated systolic hypertension in the elderly and have shown that treatment
      can reduce the risk for cardiovascular complications. An update on isolated
      systolic hypertension and the importance of detecting and treating are presented.

PMID- 11951748
TI  - Automated external defibrillators used in the community.

PMID- 11951749
TI  - Hospice and palliative research: is it worth the effort?

PMID- 11951750
TI  - What can home healthcare nurses do to contribute to their agency's success under
      PPS?

PMID- 11951751
TI  - PPS advice for clinicians. Follow the IPS road.

PMID- 11951752
TI  - PPS--positive, proactive, sharing--and success.

PMID- 11951753
TI  - Improving organizational performance standards: data aggregation and analysis.

PMID- 11951754
TI  - The future of home and hospice care. Linking interventions to outcomes.
AB  - The pressure on home care and hospice nurses to reach successful outcomes in a
      cost-effective manner mandates that they become well versed in how to analyze
      data. The goal of outcome research is to relate patient outcomes to the
      interventions provided. This article discusses the challenges of outcomes
      research and how it differs from and relates to performance improvement, and it
      explores solutions to common problems.

PMID- 11951755
TI  - A clinical pathway for deep vein thrombosis.
AB  - The use of low molecular weight heparin to treat deep vein thrombosis at home
      represents a relatively new patient population for home care agencies. Use of a
      clinical pathway provides a framework for defining expected outcomes of care and
      direction for patient assessment, care, monitoring, and documentation.
      Implementation and evaluation of a clinical pathway are described.

PMID- 11951756
TI  - The influence of organizational factors on occupational low back injuries.
AB  - The unique home care environment puts nurses at risk of low back injuries.
      Protecting nurses may mean the difference between delivering cost-effective
      quality care and no care at all. This study, conducted in Alberta, Canada,
      disclosed a lack of organizational resources and use of occupational health
      services in home care providers. Involving frontline staff as management partners
      may provide a solution for the development of an effective injury prevention
      program in home care.

PMID- 11951757
TI  - What you should know before embarking on telehome health: lessons learned from a
      pilot study.
AB  - This article provides suggestions for agencies considering telehome health as an
      adjunct to in-home nursing visits. Issues of patient and equipment selection and
      service implementation are discussed. This information represents lessons learned
      from a pilot study of telehome health with chronically ill elderly persons.

PMID- 11951758
TI  - The importance of setting boundaries in home care and hospice nursing.

PMID- 11951759
TI  - Corporate compliance and the hospice nurse.

PMID- 11951760
TI  - Designing home care processes to make organizational improvements: the Joint
      Commission Standards.

PMID- 11951761
TI  - Unresolved Medicare reimbursement issues.

PMID- 11951762
TI  - A review of the basics--understanding the categories of skilled nursing services.

PMID- 11951763
TI  - Coordination of care: the lived experience of the visiting nurse.

PMID- 11951764
TI  - Home care and hospice ethics: using the code for nurses as a guide.
AB  - In today's rapidly changing healthcare environment, home care and hospice nurses
      face complex ethical dilemmas. Many result from situations with two opposing, but
      equally reasonable, solutions. Understanding how and why ethical dilemmas arise
      helps nurses recognize the potential for an ethical dilemma and formulate
      justifiable solutions. This article, the first of a new ethics column in Home
      Healthcare Nurse, sets the foundation for the nurse's understanding of these
      dilemmas by applying the American Nurses Association's Code for Nurses with
      Interpretive Statements to real case studies.

PMID- 11951765
TI  - Mind Map: a new way to teach patients and staff.
AB  - As home care agencies look for new ways to achieve patient outcomes and staff
      competencies in a cost-effective manner, Mind Map is a method that can be used to
      quickly organize patient and staff education while evaluating the learner's
      comprehension of critical information.

PMID- 11951766
TI  - Answers to frequently asked questions about the proposed Home Care Prospective
      Payment System.

PMID- 11951767
TI  - The virtual community: helping patients use Internet support groups.

PMID- 11951768
TI  - KCI's First Step Advantage helps improve healing, saves caregivers time.

PMID- 11951769
TI  - TraxIt offers continuous-reading wearable thermometers.

PMID- 11951770
TI  - OSHA proposes ergonomics rule that will affect home and hospice.

PMID- 11951772
TI  - When should I do an OASIS assessment?
AB  - All Medicare-certified home health agencies are required to integrate the OASIS
      data set in their patient assessment. All will be held accountable for patient
      outcomes. All will soon be paid using a prospective payment methodology.
      Thoughtful implementation of OASIS activities, integrated closely with outcome
      based quality improvement and reimbursement functions, will optimize the agency's
      ability to achieve desired clinical and financial goals.

PMID- 11951771
TI  - Using OASIS for outcome-based quality improvement.
AB  - OASIS was developed for the purpose of measuring and enhancing outcomes of
      patients receiving home health services. OASIS-derived outcome reports provide a
      foundation of Outcome-based Quality Improvement (OBQI). This article describes
      the OBQI process and provides two case studies to illustrate how agencies can use
      OBQI to enhance patient care.

PMID- 11951773
TI  - Integrating OASIS data collection into a comprehensive assessment.
AB  - OASIS should not be used as a survey tool; rather, it should be integrated into a
      comprehensive assessment. It is almost never appropriate to simply read OASIS
      questions verbatim to patients and expect them to name the letter of the
      response. This article provides strategies for collecting OASIS data as part of a
      routine patient comprehensive assessment.

PMID- 11951774
TI  - Unexpected benefits of OASIS and OBQI.
AB  - While implementing OASIS data collection and OBQI, agencies participating in the
      national demonstration project found that unexpected benefits occurred that had
      major impacts on their organizations. This article provides a discussion of the
      clinical, managerial, and administrative benefits the agencies identified.

PMID- 11951775
TI  - We've collected the OASIS data, now what?
AB  - The OASIS data set provides home care agencies with well-tested items for the
      collection of patient health status and outcome data. Illustrative examples of
      some of the OASIS-derived reports that agencies participating in demonstration
      projects received are presented. By understanding these reports, clinicians can
      see how the information they collect is presented in reports and can better
      understand the importance of collecting complete and accurate data.

PMID- 11951776
TI  - A practical look at outcome enhancement for rehospitalization. Spotlight on VNA
      health care.

PMID- 11951778
TI  - OASIS--our agency's experience.

PMID- 11951779
TI  - How best to support bereaved children.

PMID- 11951780
TI  - The use of epidural and intrathecal analgesia in palliative care.
AB  - Oral analgesics and adjunctive medicines will be used to meet the needs of most
      palliative care patients in terms of pain relief. However, for a small number of
      patients, this will not be adequate for satisfactory relief from pain, resulting
      in a lower quality of life. For such patients, using some of the more 'technical
      approaches' to pain relief, e.g. epidural or intrathecal analgesia, can prove
      beneficial. Taking the anatomy of the spinal space into consideration, this
      article will present the indications and contraindications for spinal analgesia,
      as well as drugs used and the most appropriate methods of drug administration.

PMID- 11951781
TI  - Effective palliative care for minority ethnic groups: the role of a liaison
      worker.
AB  - As the issue of equality of access to health-care services becomes more
      important, there is increasing concern that specialist palliative care services
      in the UK are under-used by minority ethnic groups (Haroon-Iqbal et al, 1995;
      Karim et al, 2000). Research into the provision of such services for black and
      minority ethnic communities identified a number of factors that contribute to a
      perceived low take-up of services (Hill and Penso, 1995). A strategy to promote
      ethnic and racial sensitivity in palliative care service delivery, and policies
      to improve access to, and take-up of, services was recommended. This article
      presents the important elements relating to equal access to specialist palliative
      care and the provision of culturally sensitive services, and examines the role of
      the Macmillan Ethnic Minorities Liaison Officer in the Bradford community
      palliative care team.

PMID- 11951782
TI  - Skin changes in lymphoedema: pathophysiology and management options.
AB  - Appropriate skin care and prevention of infection are important cornerstones of
      effective lymphoedema management, which can play a vital role in patient comfort
      and acceptance of swelling. Management of the patient or client with lymphoedema
      requires input from an appropriately qualified and skilled practitioner, however
      skin care is one area of care, which may be addressed by all levels of healthcare
      professionals involved in direct patient care. This article highlights the
      pathophysiology of both the skin and lymphatics in lymphoedema. It also aims to
      give the reader a practical understanding of potential skin problems and
      suggestions for how they may be identified and remedied.

PMID- 11951783
TI  - Bridging the research-practice gap: breaking new ground in health care.
AB  - Many theorists have discussed the existence of a gap between nursing research and
      practice. Consequently much time and effort has been expended in trying to devise
      strategies to bridge this divide. This article explores what the research
      practice gap is and discusses five important reasons for it. The issue is then
      raised as to whether or not there is a gap between evidence and practice, despite
      the existence of the gap between research and practice. This is explored in
      relation to the potential conflict between the 'know how' knowledge important in
      practice and the 'know that' knowledge important in academia. Finally, the
      concept of practitioner-centred research is described as one strategy that would
      effectively obliterate the research-practice gap as it is currently conceived.

PMID- 11951784
TI  - An audit of oral care practice and staff knowledge in hospital palliative care.
AB  - Mouth care is considered one of the most basic of nursing activities, and
      palliative care patients are especially vulnerable to oral problems (Macmillan
      Practice Development Unit, 1995). This article describes a project on developing
      oral care practice and staff knowledge, by nursing staff and Macmillan nurses at
      a hospital in central England. A baseline audit (audit I) was carried out to
      examine all aspects of current oral care practice and nursing knowledge,
      including assessment, implementation, prescribing and evaluation of care. Oral
      care guidelines and a programme of ward-based teaching were then introduced.
      Several months later a follow-up audit (audit II) was conducted. Results showed
      an improvement in all aspects of oral care and staff knowledge. Additional
      benefits of this process included improved professional relationships and the
      promotion of further audits in hospital palliative care. Recommendations include
      the need for further nursing research into oral care to build the evidence base
      further. Additionally, it is suggested that nurses must recognize their important
      and central role in improving this aspect of palliative care. Education and
      training is pivotal to this process.

PMID- 11951785
TI  - Education in palliative care: making a difference to practice?
AB  - This article presents part of a multiphase evaluation project, which aims to
      investigate the effectiveness of a number of palliative care educational
      programmes provided by a hospice education network in the north of England.
      Information is reported from four cohorts of students (n = 46) who undertook
      courses between October 1998 and April 2000. Particular emphasis was placed on
      the views of students and whether education made a difference to their clinical
      practice. An action research approach was used which asked the question 'Does
      education develop competent confident practitioners, who are able to initiate
      changes in their practice?' Early indications suggest that education does make a
      difference to practice. Students reporting feeling more confident, having a
      greater knowledge of palliative care and being more skilled in caring for
      patients and their families. Furthermore, students have made recognizable changes
      to their practice, some of which are detailed here.

PMID- 11951786
TI  - A very perplexing problem.

PMID- 11951787
TI  - Prescription for the future.

PMID- 11951788
TI  - Second national "report card". Arkansas' clinical performance still needs
      improvement.

PMID- 11951789
TI  - Ace inhibitors in cardiovascular diseases.
AB  - Renin-angiotensin blockade is an important component of management of heart
      failure in the 21st century. It can be achieved by angiotensin-converting enzyme
      inhibition (ACEI) and angiotensin receptor blockade (ARB). Neuro-hormonal
      activation was considered a necessary mechanism for survival of patients with
      left ventricular dysfunction in 1960s and 1970s. This has been proven to be
      incorrect, and in fact, there is a large and growing body of evidence showing the
      cardio-protective effects of RAS and other neuro-hormonal blockade.

PMID- 11951790
TI  - Prostate cancer in Arkansas.
AB  - Prostate cancer is the most common cancer affecting men and the second leading
      cause of cancer deaths in U.S. males. Nationally, black men have greater prostate
      cancer incidence/mortality than other men. This study used focus group
      discussions to examine knowledge, beliefs and attitudes about prostate cancer in
      black and white male populations in urban and rural areas of Arkansas. The study
      found a general lack of knowledge about prostate cancer and its symptoms,
      screening and treatment. There were also subtle differences among the groups that
      could impact the development of interventions and policies, thus decreasing
      prostate cancer mortality in Arkansas.

PMID- 11951791
TI  - Histopathologic alterations after endovascular radiation and antiproliferative
      stents: similarities and differences.
AB  - BACKGROUND: Endovascular radiation and drug-eluting antiproliferative stents in
      experimental animals (normal pigs and rabbit arteries) show a decrease in the
      neointimal growth at 1 month vs. controls. However, this is accompanied by
      delayed healing characterized by persistence of neointimal fibrin (with or
      without inflammation), a decrease in smooth muscle cells, and incomplete
      endothelialization. Conversely, stainless steel control stents show complete
      healing with the neointima consisting of smooth muscle cells in a proteoglycan
      collagen matrix and near complete luminal surface endothelialization. RESULTS:
      Long-term (3 and 6 months) animal studies fail to show any benefit with radiation
      or drug-eluting stents. These experimental results are discrepant from those seen
      clinically in man where both therapies have shown benefit at 6 months, suggesting
      that animal data may not be predictive of clinical results. The main differences
      can be explained on the basis of preclinical studies performed in juvenile
      animals without underlying atherosclerosis, which leads to accelerated healing in
      animals vs. man such that 1 month animal data likely correspond to 6 months in
      man. Therefore long-term (24-30 months) angiographic and/or IVUS follow-up
      studies in man will be required to determine if drug-eluting stents will behave
      similarly to animal studies at 3 and 6 months.

PMID- 11951792
TI  - [Radioactive stents: problems and potential solutions].
AB  - BACKGROUND: The implantation of radioactive stents was the first procedure of a
      coronary brachytherapy in Europe examined in multicenter clinical trials.
      PROBLEMS OF RADIOACTIVE STENTS: After more than 400 patients with radioactive
      stents were analyzed, it became clear that overall restenosis rates were not
      reduced. A new phenomenon called the "edge effect" or "candy-wrapper" effect was
      discovered, which later was also described for catheter-based brachytherapy.
      Currently, the implantation of radioactive stents for the prevention of
      restenosis cannot be recommended. DRUG ELUTING STENTS: Although technical
      improvements of radioactive stents are theoretically possible, novel drug coated
      stents may overcome any future research of stent-based radiotherapy. Drug eluting
      stents induce antiproliferative effects beyond the stent margins. Edge effects
      were not observed in preliminary trials. However, long-term results need to be
      awaited.

PMID- 11951793
TI  - The WRIST series--what have we learnt?
AB  - BACKGROUND: The evolution of the WRIST (Washington Radiation for In-Stent
      Restenosis Trial) series has reflected the progress that has been made in
      intracoronary radiation for In-stent restenosis of coronary artery and saphenous
      vein graft disease. We have enrolled over 1,500 patients in eleven WRIST series
      performed at the Washington Hospital Center, providing a unique and powerful data
      set that is pivotal in our understanding of vascular brachytherapy. AIM: This
      review is intended to give an overview of the individual trials, summarize
      pertinent lessons that have been learned and give insight into future of
      intracoronary radiation.

PMID- 11951794
TI  - [Intracoronary radiation therapy in controlled and open clinical trials with
      afterloading systems and "hot" balloon catheters. Analysis of 6,692 patients].
AB  - The prevention and treatment of a restenosis, which occurs in ca. 30% of the
      cases following balloon dilatation of coronary stenoses, using intravascular
      radiation relies on the inhibition of proliferation that is inherent in every
      radiation therapy. The analysis is based on 6,692 patients assigned to either a
      control group (1,717 patients) or to radiation therapy (4,975 patients) in 41
      studies. A total of 14 placebo-controlled, randomized and 27 open trials have
      been completed: 22 regarding in-stent restenosis, ten regarding de-novo stenosis
      (or restenosis without a stent) as strict inclusion criteria, and nine with all
      types of stenoses. For in-stent restenoses, vessel size as defined for inclusion
      was between 2.0 mm and 5.5 mm, stenosis length between 10 mm and 80 mm. In all
      trials with in-stent restenosis, the primary endpoints were reached; the
      restenosis rate in the longest coronary segment analyzed was between 45% and 100%
      in the control groups and between 7.7% and 53.5% in the brachytherapy groups. The
      respective values for the TVR were between 24.1% and 80% in the control groups
      and between 2.0% and 41.7% in the brachytherapy groups. In the control groups,
      MACE was between 25.9% and 80%; it was between 2.0% and 41.7% in the
      brachytherapy groups. Attaining results for de-novo stenoses was problematic due
      to "geographic miss" apparently playing a larger role in these cases; but when
      taking this into consideration, good results were also attained. The known
      limitations due to late stent thromboses (4-15% in older trials) were to the most
      part eliminated by administration of clopidogrel for 1 year and the limitations
      due to the "edge effect" by the application of longer radiation sources. With
      antiproliferative coated stents as treatment for de-novo stenoses, we can count
      on intracoronary brachytherapy losing significance in this area. But for in-stent
      restenoses, intracoronary brachytherapy is the only evidence-based interventional
      form of therapy.

PMID- 11951795
TI  - Present status of endovascular brachytherapy in peripheral arteries.
AB  - BACKGROUND: Peripheral artery disease based on atherosclerosis is one of the
      major problems in angiology. Endovascular brachytherapy has shown to be a
      promising new treatment method for prevention of restenosis after femoropopliteal
      angioplasty. METHOD: Brachytherapy for peripheral arteries is performed by using
      an iridium-192 gamma source delivered with a remote controlled afterloading unit.
      Semiflexible 5F radiation catheter without centering possibility and specially
      designed 7F centering radiation delivery catheter with segmented balloons are
      available. After angioplasty patient is transported to the brachytherapy unit
      equipped with specific shielded walls. For treatment planning the whole length of
      intervention (interventional length = IL) plus safety margins is assumed to be
      the target. Dose should be related to a certain radial depth (2 mm) from the
      vessel lumen into vessel wall as proposed in the EVA GEC ESTRO Recommendations.
      Treatment planning is performed based on the vessel lumen diameter, IL safety
      margins and reference isodose length (RIL). RESULTS: First clinical experience
      with endovascular brachytherapy was obtained in Frankfurt and showed significant
      improvement of arterial patency even after a long follow-up period. The Vienna-2
      study was the first prospective, randomized trial proofing 48% relative reduction
      of restenosis in the brachytherapy arm. The results of ongoing trials using
      centering catheter (Vienna-3, PARIS) are soon expected and will definitely
      determine the role of endovascular brachytherapy for restenosis prevention after
      angioplasty.

PMID- 11951796
TI  - [Indicators of plaque stability].

PMID- 11951797
TI  - [Optimal intravascular brachytherapy: safety and radiation protection,
      reliability and precision guaranteed by guidelines, recommendations and
      regulatory requirements].
AB  - BACKGROUND: The success of intravascular brachytherapy relies entirely on the
      interdisciplinary approach. Interventional cardiologists, radiation oncologists
      and medical physicists must form a team from day 1. All members of the team need
      special knowledge and regular training in the field of vascular radiation
      therapy. Optimization of intravascular brachytherapy requires the use of
      standardized methods of dose specification, recording and reporting. This also
      implies using standardized methods of source calibration in terms of absorbed
      dose to water and having methods for simple internal control of the dosimetric
      quantities of new or replaced sources. Guidance is offered by international
      recommendations (AAPM TG 60, DGMP Report 16, NCS and EVA GEC-ESTRO). LEGAL
      REQUIREMENTS FOR RADIATION PROTECTION--WHAT'S NEW?: In Europe, new legal
      requirements on radiation protection issues have to be fulfilled. For Germany,
      the revised "Strahlenschutzverordnung" has been released recently. Nearly all
      organizational and medical processes are affected. For intravascular
      brachytherapy, several changes of requirements have to be considered. However, to
      follow these requirements does not cause serious problems. DGMP REPORT 16:
      GUIDELINES FOR MEDICAL PHYSICAL ASPECTS OF INTRAVASCULAR BRACHYTHERAPY:
      Evaluation of clinical results by comparison of intravascular brachytherapy
      treatment parameters is possible only if the prescribed dose and the applied dose
      distribution are reported clearly, completely and uniformly. The DGMP guidelines
      thus recommend to prescribe the dose to water at the system related reference
      point PRef at 2 mm radial distance for intracoronary application (and at 5 mm for
      peripheral vessels). The mean dose at 1 mm tissue depth (respectively at 2 mm)
      should be reported in addition. To safely define the planning target volume from
      the injured length, safety margins of at least 5 mm (10 mm) have to be taken into
      account on both ends. Safety margins have also to be considered for
      multisegmental treatment, to omit underdosage. IVUS based localization will
      support precise planning, avoid a geographic miss and edge effects and will allow
      for later evaluation. These DGMP recommendations are also included in the EVA GEC
      ESTRO recommendations and in the draft for an up-date of the AAPM TG 60 report.
      CONCLUSION: Medical physical quality management of intravascular brachytherapy is
      a necessary condition for optimal and safe treatment. Procedures, devices, and
      sources should fulfill the same degree of precision and safety as common in
      radiotherapy.

PMID- 11951798
TI  - Publication of current prosthodontic research.

PMID- 11951799
TI  - A comparison of three-dimensional finite element stress analysis with in vitro
      strain gauge measurements on dental implants.
AB  - PURPOSE: The purpose of this study was to evaluate the compatibility of three
      dimensional finite element stress analysis and in vitro strain gauge analysis in
      the measurement of strains on a dental implant. MATERIALS AND METHODS: Two
      vertically placed implants embedded in a poly(methyl methacrylate) model were
      used. Strain gauges were bonded to the cervical parts of the implants, and seven
      cement-retained fixed partial dentures were fabricated. A three-dimensional model
      of the strain gauge analysis model was constructed, and an additional model in
      which human bone simulation was provided was also constructed. A static vertical
      load of 50 N was applied at certain locations to simulate centrally positioned
      axial and laterally positioned axial loading for strain gauge analysis and three
      dimensional finite element stress analysis. RESULTS: Statistically significant
      increases in strain levels were recorded between loading types in the strain
      gauge analysis (P < .05). Strains obtained from strain gauge analysis were higher
      than for three-dimensional finite element stress analysis. There was a remarkable
      difference between the two finite element models under the conditions of
      laterally positioned axial loading. CONCLUSION: There are differences regarding
      the quantification of strains between strain gauge analysis and three-dimensional
      finite element stress analysis. However, there is a mutual agreement and
      compatibility between three-dimensional finite element stress analysis and in
      vitro strain gauge analysis on the determination of the quality of induced
      strains under applied load.

PMID- 11951800
TI  - Computer-aided direct ceramic restorations: a 10-year prospective clinical study
      of Cerec CAD/CAM inlays and onlays.
AB  - PURPOSE: The objective of this follow-up study was to examine the performance of
      Cerec inlays and onlays in terms of clinical quality over a functional period of
      10 years. MATERIALS AND METHODS: Of 200 Cerec inlays and onlays placed in a
      private practice between 1989 and early 1991, 187 restorations were observed over
      a period of 10 years. The restorations were fabricated chairside using the Cerec
      1 computer-aided design/manufacturing (CAD/CAM) method and Vita MK I feldspathic
      ceramic. An adhesive technique and luting composite resin were used for seating
      the restorations. After 10 years, the clinical performance of the restorations
      was evaluated using modified USPHS criteria. The results were used to classify
      success and failure. RESULTS: According to Kaplan-Meier analysis, the success
      rate of Cerec inlays and onlays dropped to 90.4% after 10 years. A total of 15
      (8%) failures were found in 11 patients. Of these failures, 73% were caused by
      either ceramic fractures (53%) or tooth fractures (20%). The reasons for the
      remaining failures were caries (20%) and endodontic problems (7%). The three
      surface Cerec reconstructions were found to have the most failures. CONCLUSION:
      The failure rate of 8% and the drop of the survival probability rate to 90.4%
      after 10 years of clinical service of Cerec-1 CAD/CAM restorations made of Vita
      MK I feldspathic ceramic appear to be acceptable in private practice. This is
      particularly true in light of the very high patient satisfaction.

PMID- 11951801
TI  - Optical data acquisition for computer-assisted design of facial prostheses.
AB  - PURPOSE: The conventional impression technique for manufacturing facial
      prostheses has the disadvantage of deforming the soft tissues because of the
      tension caused by the impression material, as well as causing discomfort to the
      patient. The purpose of this study was to establish a system that allows contact
      free reproduction of the facial surface combined with computer-assisted design
      and fabrication of facial prostheses. MATERIALS AND METHODS: Three-dimensional
      data of the facial surface were obtained using an optical acquisition system
      based on the method of phase-measuring profilometry. A sensor head with a fringe
      projector and two CCD cameras for photogrammetric triangulation were used in
      connection with a PC for measurement control and data evaluation. Software for
      computer-assisted design of the facial surface to be reconstructed was developed.
      A prototype facial prosthesis was fabricated using stereolithography. The system
      was tested using a modified puppet head. First clinical tests were performed with
      a patient who had undergone maxillofacial surgery including the resection of one
      eye. RESULTS: Three-dimensional data acquisition and imaging allow visualization
      of a whole face without causing tension or neuromuscular reaction. As surface
      brightness is also part of the digital model, it is even more realistic than a
      plaster cast. The stereolithographic object showed good marginal fit and
      satisfactory shape. CONCLUSION: The presented technique allows three-dimensional
      data reproduction of the facial surface, computer-assisted design of a facial
      prosthesis, and transfer to a rapid prototyping unit. The system has obvious
      advantages over conventional impression techniques. Further clinical trials are
      planned to evaluate the clinical success of the technique.

PMID- 11951802
TI  - A prospective 5-year study of two cast framework alloys for fixed implant
      supported mandibular prostheses.
AB  - PURPOSE: A longitudinal 5-year clinical investigation was carried out to compare
      screw-retained frameworks constructed from two alloys with different mechanical
      properties, either gold or silver-palladium, supported in the mandible by the
      Astra Tech implant system. MATERIALS AND METHODS: Twenty-six edentulous patients
      with mandibular implants were divided into two groups: group A was provided with
      Chicago IV gold alloy superstructures, and group B was provided with Palliag M
      silver-palladium alloy superstructures. The surgical procedures for placing the
      mandibular bone implants and the prosthodontic and laboratory techniques for
      constructing the prostheses were carried out according to standard, well
      documented practices. All patients wore conventional maxillary complete dentures.
      The integrity of prostheses and health of supporting tissues were compared over a
      5-year period. RESULTS: Both materials had similar accuracy of fit and resistance
      to functional stress, although silver-palladium was technique sensitive and
      necessitated meticulous laboratory practice to achieve accuracy of casting.
      Clinical performance of both prostheses was similar, and radiographic assessment
      showed no statistically significant differences in periimplant bone changes.
      CONCLUSION: There were no differences in clinical performance and radiographic
      changes between the two materials. Therefore, silver-palladium alloy may be
      considered a suitable low-cost substitute for gold alloy for fixed implant
      supported prostheses.

PMID- 11951803
TI  - Speech outcomes in patients rehabilitated with maxillary obturator prostheses
      after maxillectomy: a prospective study.
AB  - PURPOSE: Speech outcome measurements are valuable in guiding treatment and
      determining the effectiveness of rehabilitation with a maxillary obturator
      prosthesis in individuals with palatal resection. Although speech outcome data
      exist in the literature for such patients, relatively few reports have used
      clinical tools designed to measure the acoustic, physiologic, and perceptual
      bases of speech. This investigation reports these measures for individuals
      rehabilitated with a maxillary obturator. MATERIALS AND METHODS: Speech
      measurements were collected prospectively at three clinical visit times
      (preoperative, postresection without an obturator, and with a definitive
      obturator) for 12 patients assigned to three groups based on the extent of their
      resection (< half the hard palate, > or = half the hard palate, hard and soft
      palates). Acoustic data were obtained with the Nasometer, aeromechanical data
      were collected with the PERCI-SARS, and perceptual ratings of speech
      intelligibility were obtained through listener analysis. RESULTS: Significant
      differences existed among the three treatments for all dependent variables and
      revealed that speech without an obturator is significantly different from the
      preoperative state, while speech with an obturator does not differ significantly
      from preoperative function. Individuals with soft palate involvement exhibited
      significantly poorer nasalance values than individuals with involvement of the
      hard palate only. CONCLUSION: Rehabilitation with a maxillary obturator is
      successful in restoring preoperative speech function. Rehabilitation of
      individuals with involvement of the soft palate may be more challenging.

PMID- 11951804
TI  - Oral prosthetics from a Nordic perspective.
AB  - PURPOSE: The purpose of this study was to describe oral prosthetics in a context
      intended for other, primarily Nordic, health professionals and health
      authorities. MATERIALS AND METHODS: An article describing oral prosthetics for
      the general public was formulated on the basis of recent data and publications in
      prosthodontics from Scandinavian authors. A draft was presented to the
      educational committee of the Scandinavian Society for Prosthetic Dentistry for
      verification and consensus. Following modifications and amendments by
      representatives from the 11 dental schools in the Nordic countries, the
      educational committee has approved the present article. RESULTS: The report
      consists of four sections describing oral prosthetics, prosthetic therapy,
      undergraduate teaching in oral prosthetics, and advanced oral prosthetics, from a
      Nordic perspective. The report appraises the various factors in context with
      demographic, cultural, and professional circumstances and suggests strategies for
      improvement of present conditions. CONCLUSION: The relationship between the
      undergraduate curriculum in oral prosthetics and the public need for advanced
      oral prosthetics must continuously be monitored so that patients can obtain
      optimal care from the profession.

PMID- 11951805
TI  - Investigation of the fracture resistance of three types of zirconia posts in all
      ceramic post-and-core restorations.
AB  - PURPOSE: All-ceramic post-and-core restorations offer a number of advantages
      compared with systems that use metal cores. In certain clinical cases, however,
      fractures at the junction between the post and the core have been reported. The
      objective is therefore to improve the strength between the post and the core.
      MATERIALS AND METHODS: Three different methods were used to fabricate all-ceramic
      post-and-core restorations: pressing IPS Empress cores directly to CosmoPost
      zirconia posts, adhesively luting IPS Empress cores to CosmoPost zirconia posts,
      and Celay milling In-Ceram zirconia blanks to one-piece post-and-core
      restorations. Ten restorations were prepared with each of the three methods. The
      post-and-core complexes were tested to failure with the load applied
      perpendicular to the post axis. The load and deflection at fracture were
      recorded. RESULTS: The highest breaking load and highest deflection were recorded
      for the luting technique, with values of 25.3 N and 394 microns, respectively.
      The corresponding values for the pressed cores and the milled zirconia cores were
      22 N and 301 microns, and 13 N and 160 microns. All differences were
      statistically significant at P < .05. Regarding the load dependence of the
      deflection, the luted cores again demonstrated the highest mean value, with 15.5
      microns/N, while this value was 13.6 microns/N and 13 microns/N for the pressed
      on and milled cores, respectively. These differences were not statistically
      significant. CONCLUSION: Adhesively luted all-ceramic cores on zirconia posts
      offer a viable alternative to the conventional pressed technique.

PMID- 11951806
TI  - Microstructure, composition, and etching topography of dental ceramics.
AB  - PURPOSE: Topographic analysis of etched ceramics provides qualitative surface
      structure information that affects micromechanical retention mechanisms. This
      study tested the hypothesis that the etching mechanism changes according to the
      type of etchant and the ceramic microstructure and composition. MATERIALS AND
      METHODS: Quantitative and qualitative analyses of 15 dental ceramics were
      performed using scanning electron microscopy, back-scattered imaging, X-ray
      diffraction, optical profilometry, and wavelength dispersive spectroscopy based
      on Phi-Rho-Z correction. All ceramic specimens were polished to 1 micron with
      diamond compound, and the following etchants and etching times were used:
      ammonium bifluoride (ABF) for 1 minute, 9.6% hydrofluoric acid (HF) for 2
      minutes, and 4% acidulated phosphate fluoride (APF) for 2 minutes. RESULTS: HF
      produced an irregular etching pattern in which pores were the characteristic
      topographic feature. ABF-etched ceramic surfaces showed mostly grooves, and APF
      etchant caused a buildup of surface precipitate. Core ceramics showed less
      topographic change after etching because of their high alumina content and low
      chemical reactivity. CONCLUSION: The observations suggest that the etching
      mechanism is different for the three etchants, with HF producing the most
      prominent etching pattern on all dental ceramics examined.

PMID- 11951807
TI  - In vitro study on the dimensional accuracy of selected materials for monophase
      elastic impression making.
AB  - PURPOSE: This study evaluated the dimensional accuracy of various impression
      materials for monophase elastic impression making. To isolate this parameter, a
      direct measurement of the impressions was made without taking the model material
      into consideration. MATERIALS AND METHODS: A total of eight materials were
      tested; six impression materials were addition-curing silicones, and two were
      polyether impression materials. All materials were processed according to the
      manufacturers' instructions. A specially developed precision mold made of
      stainless steel served as basis for measuring the elastomeric impression
      materials. Using a stereomicroscope at a temperature of 23.0 +/- 1.0 degrees C
      and with a precision linear adjustment and lathe, sights were set on the marking
      points of customized posts. The measurement was performed after the earliest time
      possible for fabricating the model according to the manufacturer (time 1) and
      after 90 minutes (time 2). In a one-way analysis of variance, multiple average
      comparisons of dimensional accuracy were made (P < or = .05) between the
      impression materials under investigation. RESULTS: Under the conditions of this
      study, the impression materials tested demonstrated a very high dimensional
      accuracy. The arithmetic means of the dimensional changes ranged from -11 to 19
      microns for both measuring times. CONCLUSION: Since as a rule, no significant
      dimensional changes occurred for the different impression materials between time
      1 and time 2, this time interval for fabricating a model can be recommended.

PMID- 11951808
TI  - Effect of core bonding on fatigue failure of compromised teeth.
AB  - PURPOSE: This study determined the effect of bonding a composite core on the
      number of load cycles to cement failure for teeth restored with complete crowns.
      MATERIALS AND METHODS: Ten extracted human maxillary central incisors were
      divided into two groups of five each. The tooth roots were at least 11 mm long,
      allowing an 8-mm post. Under copious irrigation, each tooth was cut to a flat
      plane 1 mm coronal to the buccal cementoenamel junction, perpendicular to the
      long axis of the tooth. The canal space was prepared to a final diameter of 1.25
      mm, 8 mm deep. Each tooth was rebuilt with a 050 Parapost and Corestore. Final
      preparation height was 7 mm, including a 1-mm ferrule. For group 1, the core was
      bonded to the dentin using autocured Scotchbond Multipurpose Plus. For group 2,
      the core was not bonded. Following crown cementation, all teeth were subjected to
      a fatigue load of 4 kg at a rate of 280 cycles per minute. RESULTS: One tooth
      with a bonded core failed at 19,880 cycles, and the other four in this group did
      not fail after 100,000 cycles. All of the teeth without a bonded core failed at a
      cycle count of less than 100. The Mann-Whitney nonparametric test showed a
      significant difference between the two groups (P < .01). CONCLUSION: Bonding of a
      composite core to dentin prior to crown cementation provided a significantly
      stronger crown retention under fatigue loading.

PMID- 11951809
TI  - Probability of failure of highly filled indirect resin-veneered implant-supported
      restorations: an in vitro study.
AB  - PURPOSE: The study compared the probability of failure of three highly filled
      resin-veneered restorations to that of conventional metal-ceramic restorations
      when used as implant-supported prostheses. The effect of the location of load
      application on the fracture resistance of the restorations was also studied.
      MATERIALS AND METHODS: Twenty samples each of the three resins, Artglass, Targis,
      and Estenia, were applied on type IV gold frameworks. Twenty metal-ceramic
      restorations of equal dimensions (VMK 95 and Degudent Universal) were used as
      controls. Compressive load was applied vertically at 1 mm (n = 10) and 2 mm (n =
      10) from the periphery of the occlusal table until the restorations failed.
      Weibull analysis was applied to the data. RESULTS: There was no significant
      difference in the probability of failure among the metal-ceramic restorations and
      three resin-veneered restoration systems. Loading the resin-veneered restorations
      at the 1-mm location significantly increased their probability of failure when
      compared to the 2-mm loading location. The loading location did not significantly
      change the probability of failure of the metal-ceramic restorations. CONCLUSION:
      The probability of failure of resin-veneered restorations tested was not
      significantly different from that of the metal-ceramic restoration under two
      compressive loading conditions. Eccentric loading of resin-veneered restorations
      should be minimized in light of the higher probability of failure associated with
      such a loading condition.

PMID- 11951810
TI  - Flexural strength of In-Ceram alumina and In-Ceram zirconia core materials.
AB  - PURPOSE: The study compared the flexural strength of In-Ceram alumina and In
      Ceram zirconia systems. The probability of failure of the two glass-infiltrated
      ceramic core materials was analyzed with and without lamination with Vitadur
      alpha porcelain. MATERIALS AND METHODS: Ten uniform beams of core materials as
      well as 10 beams of laminated core materials were fabricated for In-Ceram alumina
      and In-Ceram zirconia. The samples were subjected to three-point bending tests.
      Flexural strength for both ceramic core materials was determined with and without
      their porcelain laminations. The strength data were analyzed using the Weibull
      method. Modes of failure for both systems were determined using scanning electron
      micrography. RESULTS: The strength of the In-Ceram zirconia system was
      significantly higher than In-Ceram alumina when comparing their core materials
      with and without porcelain lamination. The failure mode for both systems was
      predominantly transgranular fracture of alumina platelets. CONCLUSION: In-Ceram
      zirconia demonstrated higher flexural strength than In-Ceram alumina.

PMID- 11951811
TI  - Three-dimensional computerized stress analysis of commercially pure titanium and
      yttrium-partially stabilized zirconia implants.
AB  - PURPOSE: The purpose of this study was to use three-dimensional finite element
      analysis to analyze stress distribution patterns in Re-Implant implants made of
      commercially pure titanium (cpTi) and yttrium-partially stabilized zirconia
      (YPSZ). MATERIALS AND METHODS: Two three-dimensional finite element analysis
      models of a maxillary incisor with Re-Implant implants were made, surrounded by
      cortical and cancellous bone. A porcelain-fused-to-metal crown for the cpTi
      implant and a ceramic crown for the YPSZ implant were modeled. Stress levels were
      calculated according to the von Mises criteria. RESULTS: Higher stresses were
      observed at the area where the implant entered the bone. Stresses were higher at
      the facial and lingual surfaces than the proximal ones. In cortical bone and at
      the junction of cortical and cancellous bone, stress distribution presented a
      pattern of alternating higher (4.0 to 5.0 MPa) and lower (1.3 to 2.0 MPa) stress
      areas. Higher stresses were found at the apical third of the implant-to-bone
      junction as well. CONCLUSION: Re-Implant implants presented a pattern of low,
      well-distributed stresses along the entire implant-to-bone interface. YPSZ
      implants had very similar stress distribution to cpTi implants and may be viable
      esthetic alternatives, especially in maxillary anterior regions.

PMID- 11951813
TI  - Congenital hypoparathyroidism, associated in this case with mental retardation,
      seizure disorder, and short stature.

PMID- 11951815
TI  - Bibliography of toxinology.

PMID- 11951814
TI  - A list of animal toxins and some other natural products with biological activity.

PMID- 11951812
TI  - Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel,
      controlled-release formulation of alpha-lipoic acid.
AB  - OBJECTIVE: To determine the pharmacokinetics, safety, and tolerability of a
      novel, controlled-release oral formulation of alpha-lipoic acid (LA) and to
      investigate whether sustaining the concentration of LA in plasma would have a
      beneficial effect on glycemic control in patients with type 2 diabetes. METHODS:
      For the pharmacokinetic study, a single, 600-mg dose of either controlled-release
      LA (CRLA) or quick-release LA (QRLA) was administered orally to 12 normal human
      subjects. The plasma profile of LA was determined for 24 hours after
      administration of the dose,and pharmacokinetic analyses were performed. For the
      safety and tolerability study, 21 patients with type 2 diabetes were given 900 mg
      of CRLA daily for 6 weeks, followed by 1,200 mg of CRLA daily for an additional 6
      weeks. Active treatment was followed by a 3-week washout period. Throughout the
      study, patients continued to take their prestudy antidiabetic medications, which
      included metformin (Glucophage), sulfonylureas (Amaryl, glyburide, and
      Glucotrol), acarbose (Precose), troglitazone (Rezulin), and insulin (either as
      monotherapy or in combination). CRLA was evaluated for safety and tolerability as
      well as for effects on glycemic control. RESULTS: The Tmax (time to maximal
      plasma concentration) of LA administered as CRLA was 1.25 hours and was
      approximately 2.5-fold longer in comparison with the Tmax for QRLA (Tn,5X = 0.5
      hour; P<0.02). No severe side effects or changes in either liver or kidney
      function or hematologic profiles were noted after the administration of CRLA. In
      15 patients, the mean plasma fructosamine concentration was reduced from 313 to
      283 micromol/L(P<0.05) after 12 weeks of treatment with CRLA. CONCLUSION: CRLA
      increased the plasma concentration of LA over time in healthy subjects, and CRLA
      was safe, well tolerated, and effective in reducing plasma fructosamine in
      patients with type 2 diabetes.

PMID- 11951816
TI  - Heard it on the grapevine. Have you been CHI'd?

PMID- 11951818
TI  - Guidelines for everyday foot management.

PMID- 11951817
TI  - [Conditions for health and welfare? A survey on Black women in the State of Rio
      de Janeiro].

PMID- 11951819
TI  - Cough and haemoptysis.

PMID- 11951821
TI  - A full body scan for everyone?

PMID- 11951820
TI  - Cystic breast lesions.

PMID- 11951822
TI  - Sleep and supplements: the great melatonin debate.

PMID- 11951824
TI  - Seeking security for wandering Alzheimer patients.

PMID- 11951823
TI  - Lupus and the heart-joint connection.

PMID- 11951825
TI  - House calls. How can my total cholesterol be high if my HDL, LDL, and
      triglyceride levels are normal? Do I need treatment?

PMID- 11951826
TI  - The pathogenesis of the polycystic ovary syndrome: a hypothesis.

PMID- 11951827
TI  - Evidence-based medicine?

PMID- 11951828
TI  - Carcinoma of thyroglossal duct cyst.

PMID- 11951829
TI  - Method-independent effect in testing for detailed balance in ion channel gating.

PMID- 11951830
TI  - Mesenteric ischemia. Reduced blood flow to the gut.

PMID- 11951831
TI  - Health tips. Treating itchy scalp.

PMID- 11951833
TI  - Understanding your blood pressure measurement.

PMID- 11951832
TI  - Dangers of high-normal blood pressure.

PMID- 11951834
TI  - Eating 'outside the box'. What are the healthiest choices?

PMID- 11951835
TI  - Kidney stones. Often painful, but manageable.

PMID- 11951836
TI  - Fallen arches. When the spring leaves your step.

PMID- 11951837
TI  - Second opinion. My sister has stomach ulcers and is taking antibiotics to kill
      the bug that caused the problem. Is it true that this same bug can cause cancer,
      too?

PMID- 11951838
TI  - Second opinion. My brother was diagnosed with polycystic kidney disease. Am I at
      risk? How do I get tested?

PMID- 11951839
TI  - Tenofovir helps experienced patients.

PMID- 11951840
TI  - Illegal piercings pose risk.

PMID- 11951841
TI  - The need to communicate effectively with patients is critical.

PMID- 11951843
TI  - Time for a change in philosophy.

PMID- 11951844
TI  - Mercury and the central nervous system.

PMID- 11951845
TI  - Livestock issues. Overpowering manure.

PMID- 11951846
TI  - Metal toxicity. Unwell water in South Carolina.

PMID- 11951847
TI  - Auditory steady-state responses to exponential modulation envelopes.
AB  - OBJECTIVE: This study examined the steady-state responses evoked by tones
      modulated with exponential envelopes. The hypothesis was that stimuli with
      envelopes containing more rapid changes would evoke larger responses. DESIGN:
      Multiple auditory steady-state responses were recorded simultaneously to eight
      tonal stimuli, four in each ear. The carrier frequencies of the stimuli ranged
      from 500 to 6000 Hz and the modulation rates were between 75 and 95 Hz. The
      modulation envelopes were based on functions using sin' where N was 1, 2, 3, or
      4. Setting N to 1 produced the traditional sinusoidal modulation. RESULTS:
      Exponential envelopes with N greater than 1 produced larger steady-state
      responses than a sinusoidal envelope. For amplitude-modulation (AM), exponential
      envelopes increased response amplitudes by 21% at 55 dB pSPL, and by 29% at 35 dB
      pSPL. The increases were smaller for carrier frequencies of 1500 to 2000 Hz than
      for lower and higher carrier frequencies. Latencies calculated from phase data
      increased significantly with increasing N. This was likely caused by the point of
      maximal envelope-slope shifting later in time as N increased. For frequency
      modulation (FM), the steady-state responses did not significantly change with
      changes in the power of the exponential envelopes. CONCLUSIONS: When tones are
      amplitude-modulated with exponential envelopes based on sin(N), the amplitude and
      latency of the steady-state response increased significantly with increasing N.
      Using exponential envelopes with N greater than 1 should considerably shorten the
      time needed for responses to become significant when using steady-state responses
      in objective audiometry.

PMID- 11951848
TI  - Maturation of mismatch negativity in typically developing infants and preschool
      children.
AB  - OBJECTIVE: 1) To determine whether an adult-like mismatch negativity (MMN) can be
      reliably elicited in typically developing awake infants and preschool children,
      and if so 2) to examine whether maturational changes exist in MMN latencyand
      amplitude. DESIGN: Two experiments were designed to elicit MMN using an "oddball"
      paradigm. In Experiment 1, a 1000-Hz tone served as the standard stimulus and a
      1200-Hz tone as the deviant. In Experiment 2, a 1000-Hz standard stimulus and a
      2000-Hz deviant were presented. Infants' ages ranged from 2 to 47 and 3 to 44 mo
      in Experiments 1 and 2, respectively. RESULTS: In Experiment 1, a negativity was
      not elicited in the majority of the infants and preschoolers tested. In
      Experiment 2, a negativity was reliably elicited in the infants and preschoolers
      across all ages. A significant negative correlation was observed between age and
      latency, but not for age and amplitude for this negativity. This negativity was
      found to decrease at a rate of 1 msec/mo. Infants younger than 12 mo of age
      showed a significantly larger positivity to the deviant than to the standard
      between 150-300 and 200-300 msec in Experiments 1 and 2, respectively.
      CONCLUSIONS: The discriminative processes indexed by MMN in response to frequency
      changes areimmature in infants and preschool children. Although there is
      convincing evidence that the negativity elicited in Experiment 2 is an immature
      MMN, the possibility that it may be an "obligatory effect" indexing recovery from
      refractoriness cannot be ruled out at this time. The results from these
      experiments suggest that the MMN component haslimited use as a clinical tool at
      this time for infants and young children.

PMID- 11951849
TI  - Sound-direction identification, interaural time delay discrimination, and speech
      intelligibility advantages in noise for a bilateral cochlear implant user.
AB  - OBJECTIVES: To characterize some of the benefits available from using two
      cochlear implants compared with just one, sound-direction identification (ID)
      abilities, sensitivity to interaural time delays (ITDs) and speech
      intelligibility in noise were measured for a bilateral multi-channel cochlear
      implant user. METHODS: Sound-direction ID in the horizontal plane was tested with
      a bilateral cochlear implant user. The subject was tested both unilaterally and
      bilaterally using two independent behind-the-ear ESPRIT (Cochlear Ltd.)
      processors, as well as bilaterally using custom research processors. Pink noise
      bursts were presented using an 11-loudspeaker array spanning the subject's
      frontal 180 degrees arc in an anechoic room. After each burst, the subject was
      asked to identify which loudspeaker had produced the sound. No explicit training,
      and no feedback were given. Presentation levels were nominally at 70 dB SPL,
      except for a repeat experiment using the clinical devices where the presentation
      levels were reduced to 60 dB SPL to avoid activation of the devices' automatic
      gain control (AGC) circuits. Overall presentation levels were randomly varied by
      +/- 3 dB. For the research processor, a "low-update-rate" and a "high-update
      rate" strategy were tested. Direct measurements of ITD just noticeable
      differences (JNDs) were made using a 3 AFC paradigm targeting 70% correct
      performance on the psychometric function. Stimuli included simple, low-rate
      electrical pulse trains as well as high-rate pulse trains modulated at 100 Hz.
      Speech data comparing monaural and binaural performance in noise were also
      collected with both low, and high update-rate strategies on the research
      processors. Open-set sentences were presented from directly in front of the
      subject and competing multi-talker babble noise was presented from the same
      loudspeaker, or from a loudspeaker placed 90 degrees to the left or right of the
      subject. RESULTS: For the sound-direction ID task, monaural performance using the
      clinical devices showed large mean absolute errors of 81 degrees and 73 degrees,
      with standard deviations (averaged across all 11 loud-speakers) of 10 degrees and
      17 degrees, for left and right ears, respectively. Fore bilateral device use at a
      presentation level of 70 dB SPL, the mean error improved to about 16 degrees with
      an average standard deviation of 18 degrees. When the presentation level was
      decreased to 60 dB SPL to avoid activation of the automatic gain control (AGC)
      circuits in the clinical processors, the mean response error improved further to
      8 degrees with a standard deviation of 13 degrees. Further tests with the custom
      research processors, which had a higher stimulation rate and did not include
      AGCs, showed comparable response errors: around 8 or 9 degrees and a standard
      deviation of about 11 degrees for both update rates. The best ITD JNDs measured
      for this subject were between 350 to 400 microsec for simple low-rate pulse
      trains. Speech results showed a substantial headshadow advantage for bilateral
      device use when speech and noise were spatially separated, but little evidence of
      binaural unmasking. For spatially coincident speech and noise, listening with
      both ears showed similar results to listening with either side alone when
      loudness summation was compensated for. No significant differences were observed
      between binaural results for high and low update-rates in any test configuration.
      Only for monaural listening in one test configuration did the high rate show a
      small significant improvement over the low rate. CONCLUSION: Results show that
      even if interaural time delay cues are not well coded or perceived, bilateral
      implants can offer important advantages, both for speech in noise as well as for
      sound-direction identification.

PMID- 11951850
TI  - Middle ear dynamic characteristics in patients with otosclerosis.
AB  - OBJECTIVE: To investigate the middle ear dynamic characteristics in patients with
      otosclerosis using the sweep frequency impedance meter (SFI test) and
      conventional tympanometry, and also to evaluate the diagnostic efficiency of the
      SFI test for otosclerosis. DESIGN: The study was designed to collect a total of
      25 (36 ears) consecutive patients with otosclerosis. All subjects followed a
      clinical protocol, which consisted of a hearing problem questionnaire, otoscopic
      examination, and audiometric measurements. These included pure tone audiometry,
      conventional tympanometry, and SFI test. RESULTS: In the SFI test, the middle ear
      dynamic characteristics were measured in terms of the resonance frequency and
      middle ear mobility. Three distinct categories of middle ear dynamic
      characteristics were found in patients with otosclerosis, i.e., high stiffness,
      normal stiffness, and low stiffness middle ear status. On comparison of the
      results of SFI with conventional tympanometry, a significantly higher percentage
      of abnormal stiffness was found when using the SFI test than that when using
      conventional tympanometry. CONCLUSIONS: The present findings confirm the
      advantage of the SFI test over conventional tympanometry in detecting middle ear
      status and mechanics in patients with otosclerosis. Moreover, different middle
      ear dynamic characteristics in patients with otosclerosis are most likely to be
      related to the different stages of the pathological changes.

PMID- 11951851
TI  - Spondee recognition in a two-talker masker and a speech-shaped noise masker in
      adults and children.
AB  - OBJECTIVE: The objective of the study was to examine developmental effects for
      perceptual masking due a two-talker masker. Both continuous and gated maskers
      were employed in order to determine the importance of masker continuity for
      perceptual masking. DESIGN: A repeated measures design compared the spondee
      recognition performance of adults and children using both a speech-shaped noise
      and a two-talker masker. The masker was either presented continuously, or was
      gated on and off at about the same time as the target spondee. The ages of the
      listeners were 19 to 48 yr (adults) and 5 to 10 yr (children). RESULTS: The
      results for the continuous masker indicated higher thresholds for the two-talker
      masker than for the speech-shaped noise masker. This effect was greater in the
      children than in the adults. In the gated masking condition, the greater masking
      effect associated with the two-talker masker was either diminished (children) or
      eliminated (adults). CONCLUSIONS: These results suggest a masking effect for two
      talker speech competition that is greater in children than in adults. Perceptual
      masking is greater for continuous than for gated masking.

PMID- 11951852
TI  - EAP recordings in ineraid patients--correlations with psychophysical measures and
      possible implications for patient fitting.
AB  - OBJECTIVE: Objective measurements can be helpful for cochlear implant fitting of
      difficult populations, as for example very young children. One method, the
      recording of the electrically evoked compound action potential (EAP), measures
      the nerve recruitment in the cochlea in response to stimulation through the
      implant. For coding strategies implemented at a moderate stimulation rate of 250
      pps per channel, useful correlations between EAP data and psychophysical data
      have been already found. With new systems running at higher rates, it is
      important to check these correlations again. DESIGN: This study investigates the
      correlations between psychophysical data and EAP measures calculated from EAP
      amplitude growth functions. EAP data were recorded in 12 Ineraid subjects.
      Additionally, behavioral thresholds (THR) and maximum acceptable loudness levels
      (MAL) were determined for stimulation rates of 80 pps and 2,020 pps for each
      electrode. RESULTS: Useful correlations between EAP data and psychophysical data
      were found at the low stimulation rate (80 pps). However, at the higher
      stimulation rate (2,020 pps) correlations were not significant. They were
      improved substantially, however, by introducing a factor that corrected for
      disparities due to temporal integration. Incorporation of this factor, which
      controls for the influence of the stimulation rate on the threshold, improved the
      correlations between EAP measures recorded at 80 pps and psychophysical MALs
      measured at 2,020 pps to better than r = 0.70. CONCLUSIONS: EAP data as such can
      only be used to predict behavioral THRs or MCLs at low stimulation rates. To cope
      with temporal integration effects at higher stimulation rates, EAP data must be
      rate corrected. The introduction of a threshold-rate-factor is a promising way to
      achieve that goal. Further investigations need to be performed.

PMID- 11951853
TI  - Relationship between intensity and reaction time in normal-hearing infants and
      adults.
AB  - OBJECTIVE: Reaction time (RT) to sound is known to be related to loudness in
      adult listeners. The purpose of this study was to determine whether infants' RT
      to sound decreases systematically with intensity as it does in adults. DESIGN: RT
      was measured for 24 6- to 9-mo-old infants and 11 19- to 26-yr-old adults. All
      participants were normal hearing, naive listeners. The stimuli consisted of 4000
      and 1000 Hz pure tones presented to the right ear through an insert earphone.
      Stimulus intensities ranged in 10 dB steps from 40 to 80 dB SPL for adults and 50
      to 90 dB SPL for infants. Infant responses consisted of a head turn toward a
      reinforcer whereas adults responded by raising their hand. An additional three
      adults responded with a head turn. RT was defined as the time between the onset
      of the tone and an observer's button press indicating that a response had
      occurred. RT was corrected for the observer's reaction time and averaged over
      three to five repetitions at each level to obtain the mean reaction time (MRT)
      for each subject, frequency, and level. RESULTS: MRT decreased with increasing
      intensity in both infants and adults. An examination of the MRT-intensity
      functions suggests that the infant functions may be steeper than those of adults,
      although considerable variability exists between listeners. CONCLUSIONS: RT holds
      potential as a measure of loudness in infants. Whether differences in the MRT
      intensity slopes exist between infants and adults is unclear. Future
      investigations using methods to reduce the variability of RT measurements are
      needed to examine potential slope differences further.

PMID- 11951854
TI  - Patients utilizing a hearing aid and a cochlear implant: speech perception and
      localization.
AB  - OBJECTIVE: The purpose of this pilot study was to document speech perception and
      localization abilities in patients who use a cochlear implant in one ear and a
      hearing aid in the other ear. DESIGN: We surveyed a group of 111 cochlear implant
      patients and asked them whether they used a hearing aid on their unimplanted ear.
      The first three patients who were available were tested on word and sentence
      recognition and localization tasks. Speech stimuli were presented from the front
      in quiet and in noise. In the latter conditions, noise was either from the front,
      the right, or the left. Localization was tested with noise bursts presented at 45
      degrees from the right or left. In addition we asked the patients about their
      abilities to integrate the information from both devices. RESULTS: Speech
      perception tests in quiet showed a binaural advantage for only one of the three
      patients for words and none for sentences. With speech and noise both in front of
      the patient, two patients performed better with both devices than with either
      device alone. With speech in front and noise on the hearing aid side, no binaural
      advantage was seen, but with noise on the cochlear implant side, one patient
      showed a binaural advantage. Localization ability improved with both devices for
      two patients. The third patient had above-chance localization ability with his
      implant alone. CONCLUSIONS: A cochlear implant in one ear and a hearing aid in
      the other ear can provide binaural advantages. The patient who did not show a
      clear binaural advantage had the poorest hearing aid alone performance. The
      absolute and relative levels of performance at each ear are likely to influence
      the potential for binaural integration.

PMID- 11951855
TI  - Warfarin or aspirin for recurrent ischemic stroke.

PMID- 11951856
TI  - Warfarin or aspirin for recurrent ischemic stroke.

PMID- 11951857
TI  - Warfarin or aspirin for recurrent ischemic stroke.

PMID- 11951858
TI  - Nonsteroidal drugs and Alzheimer's disease.

PMID- 11951859
TI  - Nonsteroidal drugs and Alzheimer's disease.

PMID- 11951860
TI  - Nonsteroidal drugs and Alzheimer's disease.

PMID- 11951861
TI  - Valsartan in chronic heart failure.

PMID- 11951862
TI  - Valsartan in chronic heart failure.

PMID- 11951863
TI  - Valsartan in chronic heart failure.

PMID- 11951864
TI  - Roundtable Discussion: Blood pressure lowering by any means, or do specific
      medications make a difference?

PMID- 11951865
TI  - Inmates of the mid nineteenth-century Valencian asylum 'Hospital dels Ignoscents,
      Folls e Orats'. Is their illness diagnosable?

PMID- 11951866
TI  - Mad farming in the metropolis. Part 2: the administration of the old poor law of
      insanity in the City and East London 1800-1834.

PMID- 11951867
TI  - The history of modern psychiatry in India, 1858-1947.
AB  - This article presents an introduction to the history of Indian psychiatry. It
      suggests that this history can be divided into four main periods, 1795 to 1857,
      1858 to 1914, 1914 to 1947 and 1947 to the present day. The focus of the piece is
      on the periods 1858-1914 and 1914-1947, as it traces the main trends and
      developments of the colonial era and argues that the foundations of modern
      psychiatry in India were laid down in the period of British rule. A brief
      consideration of the post-Independence period suggests that the patterns
      established in the years of British rule have continued to influence the
      psychiatric system of modern India. Research for these conclusions is based on
      extensive archival work in Indian mental health institutions and in Indian
      records offices, as well as work conducted at the National Library of Scotland in
      Edinburgh and at the India Office Library, the Wellcome Institute Library and the
      London School of Hygiene and Tropical Medicine.

PMID- 11951868
TI  - Neuropsychiatric perspectives from nineteenth-century India: the diaries of Dr
      Charles I. Smith.
AB  - The history of disease contributes to a better understanding of the growth of
      ideas in medicine. The colonial period was marked by a rapid increase in the
      variety of diseases that were known to European practitioners. We have studied
      the diary of Dr Charles Smith who worked in Bangalore in the nineteenth century.
      We feel that some of his descriptions tally with later accounts of cysticercosis.
      He also comments on a wide range of behavioural symptoms, and attempts to
      correlate neuropathological observations to these. This neuropsychiatric
      perspective was prominent in the nineteenth century. Infective causes of
      psychiatric disorders are once again considered important; this account
      highlights the fact that similar ideas were prevalent in British India, even 150
      years ago. In addition, Dr Smith's comments describe the social mileu of
      'western' medicine in India in the early colonial period.

PMID- 11951869
TI  - John Wesley on insanity.

PMID- 11951870
TI  - Study of cases of anterograde amnesia in a disease of mental disintegration.
AB  - Pierre Janet, in his famous paper (1892) on anterograde amnesia, is concerned
      with the theme of the disintegration of the human personality. He shows that the
      weakened personality may lose the power to assimilate memories of current events.
      After a severe shock, there may supervene not only a retrograde amnesia (a
      blotting out from memory from some period before the accident), but also a
      continued or anterograde amnesia, that is to say, an inability to remember events
      occurring after the accident. Janet details the circumstances of a very
      interesting case of amnesia resulting from an attack of hysteria, brought on by
      the shock of bad news. The patient, 'Mrs. D.', had wholly lost all memory of
      events that occurred during the month and a half before her attack, and since
      that time she had only been able to remember for a few moments what was going on
      around her. Janet shows that memories which appear not to be formed are in fact
      formed; that they exist somewhere in the patient's mind with the full vividness
      of ordinary recollections, and that they may spontaneously crop up in dreams, or
      may be called out by hypnotic suggestion, or by other methods.

PMID- 11951871
TI  - Health and equality of opportunity.

PMID- 11951872
TI  - Justice, health, and healthcare.
AB  - Healthcare (including public health) is special because it protects normal
      functioning, which in turn protects the range of opportunities open to
      individuals. I extend this account in two ways. First, since the distribution of
      goods other than healthcare affect population health and its distribution, I
      claim that Rawls's principles of justice describe a fair distribution of the
      social determinants of health, giving a partial account of when health
      inequalities are unjust. Second, I supplement a principled account of justice for
      health and healthcare with an account of fair process for setting limits of
      rationing care. This account is provided by three conditions that comprise
      "accountability for reasonableness."

PMID- 11951873
TI  - Healthcare justice and rational democratic deliberation.

PMID- 11951874
TI  - Access to healthcare: going beyond fair equality of opportunity.

PMID- 11951875
TI  - Justice as cardiovascular therapy.

PMID- 11951876
TI  - Why retreat to procedural justice?

PMID- 11951877
TI  - Biopsychosocial foundations.

PMID- 11951878
TI  - Daniels on justice and healthcare: laudable goals--questionable method.

PMID- 11951879
TI  - Justice in healthcare and dimpled chads.

PMID- 11951880
TI  - Rationing problems and the aims of ethical theory.

PMID- 11951881
TI  - Justice, medicine, and medical care.

PMID- 11951882
TI  - Good policy, good process.

PMID- 11951883
TI  - No basis for justice: equal opportunity, normal functioning, and the distribution
      of healthcare.

PMID- 11951884
TI  - The social nexus of healthcare.

PMID- 11951885
TI  - Justice and human nature.

PMID- 11951886
TI  - Money for research participation: does in jeopardize informed consent?
AB  - Some are concerned about the possibility that offering money for research
      participation can constitute coercion or undue influence capable of distorting
      the judgment of potential research subjects and compromising the voluntariness of
      their informed consent. The author recognizes that more often than not there are
      multiple influences leading to decisions, including decisions about research
      participation. The concept of undue influence is explored, as well as the
      question of whether or not there is something uniquely distorting about money as
      opposed to a chance for treatment or medical care. An amount of money that is not
      excessive and is calculated on the basis of time or contribution may, rather than
      constitute an undue inducement, be an indication of respect for the time and
      contribution that research subjects make.

PMID- 11951887
TI  - How much are subjects paid to participate in research?

PMID- 11951888
TI  - It's not about the money.

PMID- 11951889
TI  - Payments to research participants: the importance of context.

PMID- 11951890
TI  - Participation as commodity, participation as gift.

PMID- 11951891
TI  - Is informed consent enough? Monetary incentives for research participation and
      the integrity of biomedicine.

PMID- 11951892
TI  - Justice for the professional guinea pig.

PMID- 11951893
TI  - Treating research subjects as unskilled wage earners: a risky business.

PMID- 11951894
TI  - Research participation and financial inducements.

PMID- 11951895
TI  - Just compensation: paying research subjects relative to the risk they bear.

PMID- 11951896
TI  - Payments to participants: beware of the Trojan horses.

PMID- 11951897
TI  - Research participation and financial inducements.

PMID- 11951898
TI  - Money, consent, and exploitation in research.

PMID- 11951900
TI  - Money and the research subject: a comment on Grady.

PMID- 11951899
TI  - On considering (what I might do for) money.

PMID- 11951901
TI  - Payment of research subjects: a broader perspective.

PMID- 11951905
TI  - What do you think is a non-disease? Defining non-diseases to avoid medicalisation
      is throwing the baby out with the bath water.

PMID- 11951904
TI  - What do you think is a non-disease? Compiling list of non-diseases is medical
      arrogance.

PMID- 11951902
TI  - The research subject as entrepreneur.

PMID- 11951906
TI  - What do you think is a non-disease? Labels create legitimacy and produce
      dependence.

PMID- 11951907
TI  - What do you think is a non-disease? Diet, lifestyle, exercise, spirituality, and
      the search for meaning are ignored at our peril.

PMID- 11951908
TI  - What do you think is a non-disease? Summary of responses.

PMID- 11951909
TI  - Non-cardiac chest pain. Patients need diagnoses.

PMID- 11951910
TI  - Non-cardiac chest pain. Rapid access clinics lead to deskilling of general
      practitioners.

PMID- 11951911
TI  - Antiplatelet therapy and atherosclerotic events.  Risks and patients' values need
      to be included in decision about aspirin for prevention of coronary heart
      disease.

PMID- 11951912
TI  - Fortification of flour with folic acid. Fortification is needed now.

PMID- 11951913
TI  - Mad farming in the metropolis. Part 1: a significant service industry in East
      London.

PMID- 11951914
TI  - Johann Ludwig Wilhelm Thudichum 1829-1901, bane of the Protagonisers.

PMID- 11951915
TI  - Emil Kraepelin's years at Dorpat as professor of psychiatry in nineteenth-century
      Russia.

PMID- 11951916
TI  - Ceramic photocell implants could restore sight.
AB  - Researchers are perfecting the use of ceramic photocells for retinal
      implantation. The work is being done at the Space Vacuum Epitaxy Center in
      Houston, TX. The photocells are the results of experiments with oxide detectors
      conducted in space using the Wake Shield Facility. Artificial retinas are
      constructed of 100,000 microscopic ceramic detectors attached to a polymer film,
      which disintegrates after implantation. Initially, four arrays will be implanted,
      totalling 400,000 detectors per eye. If successful, two additional arrays would
      be implanted. Human trials are expected to begin in 2002.

PMID- 11951917
TI  - Steering the station back on course.
AB  - Rising costs of the International Space Station prompted NASA to convene a panel
      of experts to assess the quality of ISS cost estimates and review program
      assumptions and requirements. The panel concluded that NASA was unable to
      accurately predict ISS costs or to support requests for increased funding for the
      ISS through 2006 and should maintain a U.S. core complete program with three
      person crews with 6-month stays on the ISS. International response to the panel
      report was negative with space agencies from Japan, Russia, Canada, and Europe
      taking issue with the expected impact on ISS construction and use.

PMID- 11951918
TI  - Time to initiation of thrombolysis after myocardial infarction: quality
      indicators.

PMID- 11951919
TI  - Vaccine research and development.

PMID- 11951920
TI  - Prospects for a vaccine against malaria.

PMID- 11951921
TI  - Progress towards developing a vaccine for group A streptococcus based on the M
      protein.

PMID- 11951922
TI  - Hepatitis A vaccine development: a personal perspective.

PMID- 11951924
TI  - Benchmarking ambulance call-to-needle times for thrombolysis after acute
      myocardial infarction in Australia: a pilot study.
AB  - BACKGROUND: Thrombolysis for patients with acute myocardial infarction (AMI) is
      of greatest benefit when treatment is commenced as soon as possible after symptom
      onset. The British Heart Foundation (BHF) recently set a benchmark recommending
      that eligible patients with AMI receive thrombolytic therapy less than 90 min
      after calling for medical assistance. AIMS: The purpose of this study was to
      compare the performance of an urban emergency service to this benchmark. A
      secondary objective was to determine whether patients treated outside this time
      were at a greater risk of mortality. METHODS: This study consisted of an explicit
      retrospective analysis of medical records for all patients who presented by
      ambulance to the Emergency Department (ED) of Western Hospital and received
      thrombolysis for AMI within 12 h of symptom onset. The study was conducted for
      the 18-month period between 1 January 1999 and 30 June 2000. Information
      collected included times of: (i) symptom onset, (ii) call for ambulance, (iii)
      ambulance response, (iv) transport to hospital and (v) thrombolysis, as well as
      final diagnosis and in-hospital mortality. For the purposes of this study, call
      to-needle time (CTN) was defined as the time between calling the ambulance and
      commencement of thrombolytic therapy. RESULTS: One hundred and twenty-seven
      patients met the inclusion criteria. Median CTN was 81 min (range 42-279 min).
      Sixty-four per cent of patients were treated within the 90-min benchmark. The
      relative risk of mortality for patients treated outside the 90-min benchmark was
      2.6 (95% CI 0.98-6.72). CONCLUSION: This study showed that the BHF benchmark for
      CTN was not being met for over one-third of patients in the study region, with
      potential impact on mortality after AMI. Further research is needed to establish:
      (i) whether there is relationship between longer transportation times and
      mortality, (ii) whether the findings of this study may be applied to other
      regions and (iii) what strategies might be employed to reduce CTN.

PMID- 11951923
TI  - Vaccines for HIV in the developing world.

PMID- 11951925
TI  - An audit of the use of granulocyte colony-stimulating factor in septic shock.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) stimulates the
      production of neutrophils and modulates the function and activity of developing
      and mature neutrophils. In septic shock, the immune system can be considered one
      of the failing organ systems. G-CSF improves immune function and may be a useful
      adjunctive therapy in patients with septic shock. AIM: To evaluate the
      introduction of G-CSF as an adjunct to our standard treatment for community
      acquired septic shock. METHODS: We performed a prospective data collection and
      analysis to determine whether the addition of G-CSF to our standard treatment for
      community-acquired septic shock was associated with improved hospital outcome,
      compared with an historical cohort of similar patients. We included all patients
      admitted to the Intensive Care Unit (ICU) with community-acquired septic shock
      between December 1998 and March 2000. Patients received 300 microg G-CSF
      intravenously daily for 10 days in addition to our standard treatment for
      community-acquired septic shock. G-CSF was discontinued early if the patient was
      discharged from ICU before 10 days or if the absolute neutrophil count exceeded
      75 x 10(6)/mL. RESULTS: A total of 36 patients with community-acquired septic
      shock, an average Apache 2 score of 26.7, and a predicted mortality of 0.79, were
      treated with G-CSF from December 1998 to March 2000. Hospital mortality was 31%
      compared with an historical cohort of 11 similar patients with a hospital
      mortality of 73% (P = 0.018). In the subgroup of patients with melioidosis septic
      shock, the hospital survival improved from 5% to 100% (P < 0.0001). No
      significant adverse events occurred as a result of the administration of G-CSF.
      CONCLUSION: G-CSF is a safe adjunctive therapy in community-acquired septic shock
      and may be associated with improved outcome. The use of G-CSF in septic shock
      should undergo further investigation to define subgroups of patients who may
      benefit from G-CSF. The use of G-CSF in patients with septic shock due to
      Burkholderia pseudomallei is recommended.

PMID- 11951926
TI  - Prevalence of snoring and sleep-disordered breathing in a group of commercial bus
      drivers in Hong Kong.
AB  - OBJECTIVES: To assess the prevalence of sleep-disordered breathing (SDB) and its
      associated symptoms in a group of commercial bus drivers in Hong Kong. METHODS:
      Two hundred and sixteen of 410 bus drivers from three different shifts were
      interviewed with the Sleep & Health Questionnaire (SHQ) and the Epworth
      sleepiness scale (ESS) at a Hong Kong bus depot. Seventeen subjects from each
      shift were then randomly selected for at-home sleep study using the Mesam IV
      device (Madaus Medizin-Elektronik, Freiburg, Germany). RESULTS: There were 207
      men and nine women (mean age 42.4 +/- 7.5 years; body mass index (BMI) 25.4 +/-
      4.5 kg/m2; ESS 5.3 +/- 4.2). From the SHQ it was discovered that: (i) daytime
      sleepiness was reported by 87 subjects (40%), (ii) snoring > or = 3 times per
      week was reported by 80 subjects (37%), (iii) witnessed apnoea was reported by 17
      subjects (7.9%) and (iv) 29 subjects (13.4%) reported having fallen asleep during
      driving. Among the 51 subjects who underwent the at-home sleep study: (i) 31
      subjects (61%) had respiratory disturbance index (RDI) > or = 5 per hour of
      sleep, (ii) 21 subjects (41%) had RDI > or = 10 per hour of sleep, (iii) 12
      subjects (24%) had RDI > or = 15 per hour of sleep and (iv) 35 subjects (68.6%)
      snored objectively > or = 10% of the night. Ten subjects (20%) had RDI > or = 5
      and sleepiness at work, while five subjects (9.8%) had RDI > or = 5 and ESS > 10.
      No significant differences were noted in the SHQ responses, ESS, objective
      snoring or RDI among the three groups. Multiple regression analysis showed that
      BMI and witnessed apnoea were the only positive independent predictors of RDI.
      CONCLUSIONS: This study showed a high prevalence of objective snoring and SDB in
      a group of commercial bus drivers. Neither self-reported sleepiness nor the ESS
      could identify subjects with SDB.

PMID- 11951928
TI  - Problems and potentials of complementary and alternative medicine.

PMID- 11951927
TI  - Alpha-interferon 2a and 1 3-cis-retinoic acid for the treatment of metastatic
      renal cell carcinoma.
AB  - BACKGROUND: It is suggested that immunotherapy may have a better role than
      cytotoxic chemotherapy in the treatment of metastatic renal cell carcinoma. AIMS:
      A phase II study of alpha-interferon 2a (IFN2a) and 13-cis-retinoic acid (CRA) in
      the treatment of metastatic renal cell carcinoma. METHODS: Twenty-two patients
      with no previous systemic therapy were treated with IFN2a daily at 3 million
      units (MU) and escalated to 6 and 9 MU if tolerated, together with CRA given
      orally at 1 mg/kg per day in two divided doses. Changes in quality of life were
      also assessed. RESULTS: Twenty patients were available for assessment. Three
      patients (14%) achieved a partial response and five patients (23%) had stable
      disease. No patient achieved a complete response. A durable response was observed
      in partial responders with median length of response of 44 weeks (range 32-59
      weeks). Therapy was stopped in seven (35%) patients due to treatment-related
      toxicities, and quality of life was worsened in the majority of patients.
      CONCLUSION: IFN2a and CRA has a low response rate and significant toxicity, and
      the combination as standard treatment of metastatic renal cell carcinoma is not
      recommended, despite the suggestion that CRA may lengthen the response to IFN2a.

PMID- 11951929
TI  - Meningococcal disease: treatable but still terrifying.

PMID- 11951930
TI  - Surface-active phospholipid: a Pandora's box of clinical applications. Part I.
      The lung and air spaces.
AB  - Almost everywhere in the body there are phospholipids, not only comprising the
      lipid bilayer of membranes, but also in the free state. What is seldom
      appreciated, except in respirology, is that these 'free' phospholipids are
      unusual in that many are highly surface active. Surface activity is a property of
      certain substances (surfactants), conferred by their molecular constitution and
      configuration, which predisposes them to locate at interfaces because, in doing
      so, they reduce interfacial energy. When adsorbed (reversibly bound) to solid
      surfaces, surfactants can impart many highly desirable properties that have been
      widely studied and long accepted in the physical sciences, while their commercial
      applications have withstood the test of time. These desirable properties include
      lubricity (boundary lubrication), release (antistick) and dewatering, while
      providing a barrier to corrosion, abrasion, solute transmission and to biological
      microorganisms. Many of these offer obvious roles for surface-active phospholipid
      (SAPL), ranging from a corrosion inhibitor in the stomach to a load-bearing
      lubricant in the joints. This opens a veritable 'Pandora's box' of potential
      clinical applications. Part I of this review challenges traditional beliefs in
      respirology that 'surfactant' is unique to the lung and, moreover, that its
      actions are confined to the liquid-air interface. Evidence is discussed that, by
      binding to alveolar epithelium, SAPL imparts semi-permeability needed before
      channels pumping ions can also pump water vital for maintaining fluid balance.
      Evidence is also reviewed for a lining to upper airways, sinuses and Eustachian
      tube where it can act like a standard release agent.

PMID- 11951931
TI  - Preoperative localization of parathyroid adenomas: the protagonist's view.

PMID- 11951932
TI  - Preoperative localization of parathyroid adenomas: the antagonist's view.

PMID- 11951933
TI  - Preoperative localization of parathyroid adenomas: cost-effective or just costly?

PMID- 11951934
TI  - Acute renal failure following ingestion of wild mushrooms.
AB  - We describe three cases of acute renal failure in young men who ingested wild
      mushrooms with the intent of producing hallucinations. Two cases remained
      dialysis dependent and, in these cases, renal biopsy revealed tubulointerstitial
      nephritis and fibrosis. Similar cases have been reported in other countries, but
      not in Australia. The most recognized mushroom nephrotoxin is orellanine, however
      the causative mushroom species and the actual toxin involved in these cases are
      unknown.

PMID- 11951936
TI  - A case of rat-bite fever.

PMID- 11951935
TI  - Managing a malignant orocutaneous fistula: stem the tide with octreotide?

PMID- 11951937
TI  - Acute thyroiditis caused by Streptococcus agalactiae.

PMID- 11951938
TI  - Improved psychosocial function following low-intensity, 12-week outpatient
      alcohol rehabilitation programme: preliminary report.

PMID- 11951939
TI  - A comparison of the transport and fate of polychlorinated biphenyl congeners in
      three Great Lakes food webs.
AB  - A food web bioaccumulation model was used to compare transport and fate of
      polychorinated biphenyls (PCB) congeners in three food webs in the Laurentian
      Great Lakes of North America. The model was used to quantify the contribution of
      sediment-derived and freely dissolved PCBs to the body burden of aquatic biota.
      In eastern Lake Erie (OH, USA), almost 100% of the chemical body burden of biota
      originates from sediment. In western Lake Erie, benthic invertebrates accumulated
      slightly more than half of their PCB body burden from sediment while fish
      accumulated less than half of their chemical body burden from sediment. Fish from
      Lake Ontario, Canada, accumulated less than 30% of their body burden of PCB
      congeners with log Kow < 6.4 from sediment and approximately half of their body
      burden of PCB congeners with log Kow > or = 6.4 from sediment. Field data and the
      model were also used to determine the effects of declining concentrations of PCBs
      in water and sediment on concentrations of PCBs in aquatic biota. Results
      indicate that, as concentrations of PCB congeners in the ecosystem decline, the
      role of sediment as the source of contaminant to aquatic biota increases.
      Furthermore, as sediment becomes the predominant source of contaminant to aquatic
      biota. the concentration of PCB congeners in biota tends to equilibrium with
      bottom sediment.

PMID- 11951940
TI  - Synthesis and characterization of metal sulfide clusters for toxicological
      studies.
AB  - Zinc sulfide clusters were synthesized and characterized at low micromolar
      concentrations to assess the effect of metal-sulfide ligands on metal toxicity to
      aquatic organisms in oxic environments. Recommended preparation times are greater
      than 2 h initial reaction of equimolar sodium sulfide and zinc nitrate, followed
      by oxic aeration for 3 d. Ionic strength, pH, and anoxic stabilization time were
      found to be relatively unimportant in controlling the final yield. Adsorptive
      losses of zinc sulfide (ZnS) clusters to surfaces, however, were significant for
      a variety of vessel materials and membrane filters. Ionic strength and pH were
      found to be important factors controlling the extent of adsorptive losses with
      minimal loss for pHs greater than 9 and for soft waters. The Ag(I), Cu(II), and
      Hg(II) as metal sulfides completely suppress the analysis of sulfide, whereas
      Pb(II), Mn(II), and Co(II) partially suppress the analysis of sulfide by the
      methylene blue technique. Ultraviolet and fluorescence spectra are shown for
      synthesized ZnS clusters.

PMID- 11951941
TI  - Evaluating and expressing the propagation of uncertainty in chemical fate and
      bioaccumulation models.
AB  - First-order analytical sensitivity and uncertainty analysis for environmental
      chemical fate models is described and applied to a regional contaminant fate
      model and a food web bioaccumulation model. By assuming linear relationships
      between inputs and outputs, independence, and log-normal distributions of input
      variables, a relationship between uncertainty in input parameters and uncertainty
      in output parameters can be derived, yielding results that are consistent with a
      Monte Carlo analysis with similar input assumptions. A graphical technique is
      devised for interpreting and communicating uncertainty propagation as a function
      of variance in input parameters and model sensitivity. The suggested approach is
      less calculationally intensive than Monte Carlo analysis and is appropriate for
      preliminary assessment of uncertainty when models are applied to generic
      environments or to large geographic areas or when detailed parameterization of
      input uncertainties is unwarranted or impossible. This approach is particularly
      useful as a starting point for identification of sensitive model inputs at the
      early stages of applying a generic contaminant fate model to a specific
      environmental scenario, as a tool to support refinements of the model and the
      uncertainty analysis for site-specific scenarios, or for examining defined end
      points. The analysis identifies those input parameters that contribute
      significantly to uncertainty in outputs, enabling attention to be focused on
      defining median values and more appropriate distributions to describe these
      variables.

PMID- 11951942
TI  - Effect of copper binding by suspended particulate matter on toxicity.
AB  - The kinetics of Cu(II) interactions with Susquehanna River (mid-Atlantic, USA)
      particle suspensions using the copper ion selective electrode (Cu-ISE) method
      indicated that the concentration of Cu2+ in both the suspension and filtrate was
      kinetically controlled; the reaction of Cu(II) in the suspension was faster than
      that in the filtrate. Bioassay tests were performed in continuous flow-through
      bioassay systems to examine the effect of kinetics of Cu(II) interactions with
      suspended solids on the toxicity of Cu to Ceriodaphnia dubia. The toxicity curves
      were displaced to higher total Cu concentration as the reaction time increased,
      indicating that such interaction of Cu with solids was time dependent. Further,
      the toxicity curves overlapped for reaction times of 6 and 24 h, indicating that
      the reaction was relatively rapid and that equilibrium was achieved within 6 h.
      The survival of organisms was related to the free Cu2+ concentration but deviated
      from the result for bioassays in which dissolved organic matter (DOM) rather than
      particles reacted with the added Cu(II) to affect the free Cu2+ concentration. It
      may be interpreted that, besides the toxic effect of Cu2+, particles exert
      adverse influences on the organisms.

PMID- 11951943
TI  - Kinetics of polychlorinated biphenyl dechlorination by Hudson River, New York,
      USA, sediment microorganisms.
AB  - The kinetics of polychlorinated biphenyl (PCB) dechlorination by Hudson River
      (New York, USA) sediment microorganisms were investigated using Aroclor 1242 at
      10 concentrations ranging from 0 to 900 ppm (0-11.2 micromol Cl/g sediment). The
      time course of PCB dechlorination and population growth were determined by
      congener-specific analysis and the most-probable-number technique, respectively,
      over a 44-week incubation period. Dechlorination rate (nmol Cl removed/g
      sediment/d) was a linear function of PCB concentrations similar to the
      dechlorination of Aroclor 1248 by sediment microorganisms from the St. Lawrence
      River (New York, USA). However, the rate was much slower, with the linear slope
      being only 24% that of the St. Lawrence River. The threshold concentration below
      which no dechlorination occurs was (mean +/- standard deviation) 1.06 +/- 0.18
      micromol Cl/g sediment (85 +/- 14 ppm), threefold higher than that for the
      dechlorination of Aroclor 1248. The maximum extent of dechlorination was greater
      at higher Aroclor concentrations. Dechlorinating microorganisms did not show any
      significant growth until late in the lag phase of dechlorination, and their
      maximum was greater at higher initial Aroclor 1242 concentrations. Although
      dechlorination rates were significantly lower with the Hudson River inoculum,
      when normalized to the maximum number of dechlorinating organisms, they were not
      significantly different from those for Aroclor 1248 by St. Lawrence River
      microorganisms. These results further support the idea that PCB dechlorination is
      tightly linked to the growth of dechlorinating microorganisms.

PMID- 11951944
TI  - A tropical sediment toxicity test using the dipteran Chironomus crassiforceps to
      test metal bioavailability with sediment pH change in tropical acid-sulfate
      sediments.
AB  - The wetlands of the Magela floodplain of northern Australia, which is the major
      sink for dissolved metals transported in the Magela Creek system, contain acid
      sulfate sediments. The rewetting of oxidized acid-sulfate soil each wet season
      produces acidic pulses that have the potential to alter the bioavailability of
      sediment-associated metal contaminants. Acute toxicity tests (72-h mean lethal
      concentration [LC50]) using the tropical chironomid Chironomus crassiforceps
      Kieffer showed that copper toxicity decreased from 0.64 mg/L at pH 6 to 2.30 mg/L
      at pH 4. Uranium toxicity showed a similar trend (36 mg/L at pH 6 and 58 mg/L at
      pH 4). Sediment toxicity tests developed using C. crassiforceps also showed that
      both metals were less toxic at the lower sediment pH with pore-water copper
      toxicity having a lowest-observed-effect concentration of 4.73 mg/L at pH 4
      compared to 1.72 mg/L at pH 6. However, a lower pH increased pore-water metal
      concentrations and overlying water concentrations in bioassays. Hydrogen ion
      competition on metal receptor sites in C. crassiforceps was proposed to explain
      the decrease in toxicity in response to increased H+ activity. This study
      highlights the need to consider site-specific physicochemical conditions before
      applying generic risk assessment methods.

PMID- 11951945
TI  - Environmental fate and chemistry of raloxifene hydrochloride.
AB  - Raloxifene hydrochloride is a selective estrogen receptor modulator (SERM) used
      for the prevention and treatment of osteoporosis in women. Excretion of
      raloxifene occurs through the feces of patients. Raloxifene has the potential to
      be discharged into waste treatment systems after therapeutic use. Raloxifene
      hydrochloride was investigated using a battery of studies designed to describe
      its physical/chemical characteristics and define its fate in the environment. The
      mean measured solubility of raloxifene hydrochloride (+/- standard deviation) was
      345.2 +/- 15.6 microg/ml, 13.3 +/- 0.6 microg/ml, 0.9224 +/- 0.015 microg/ml, and
      627.4 +/- 132.0 microg/ml in aqueous buffers at pH 5, 7, and 9 and in unbuffered
      water, respectively. Raloxifene exhibited a mean molar absorptivity of 34,000 and
      a wavelength absorbance maximum at 287 nm for pH 5 and 7 aqueous buffer solutions
      and 297 nm at pH 9. Mean measured Kow values were 516 +/- 17, 1,323 +/- 91, and
      1,556 +/- 135 at pH 5, 7, and 9, respectively. After 5 d at 50 degrees C,
      raloxifene hydrolyzed 8.02, 10.61, and 23.81% in pH 5, 7, and 9 aqueous buffers,
      respectively. In a 28-d hydrolysis study at 25 degrees C, the calculated first
      order hydrolysis rates were 6.92 x 10(-4), 1.70 x 10(-3), and 7.66 x 10(-3)/d,
      and the corresponding half-lives were 1,001, 410, and 90 d in pH 5, 7, and 9
      aqueous buffers, respectively. Raloxifene sorbed significantly to sewage
      treatment solids with Freundlich isotherm adsorption coefficients K between 2,000
      and 3,000. Raloxifene degraded rapidly in the presence of sewage solids. In a
      system containing 0.470 g/L sludge solids, the raloxifene biodegradation rate and
      half-life were 0.0966/h and 7.17 h, respectively. In a 28-d aerobic-aquatic
      biodegradation study containing 30 mg/L sludge solids, the raloxifene
      biodegradation rate and half-life were 0.0188/d and 37 d, respectively. Given the
      fate and behavior of raloxifene in these studies, it is anticipated that
      raloxifene would rapidly dissipate in the environment.

PMID- 11951946
TI  - Metallothionein-like metal-binding protein in the biomonitor Chaoborus:
      occurrence and relationship to ambient metal concentrations in lakes.
AB  - Larvae of the insect Chaoborus are used to monitor cadmium (Cd) in lakes. We set
      out to determine if this animal possesses a metallothionein-like protein to which
      its Cd could be bound and if the concentrations of such a protein are correlated
      with those of Cd in the insect and in lakewater. To achieve our goals, we
      collected water and larvae of several Chaoborus species from 10 lakes situated
      along an environmental Cd gradient. We found that all of the Chaoborus species
      possess a metallothionein-like protein and that concentrations of the protein and
      of Cd differed among species. Concentrations of the metallothionein-like protein
      were directly related to those in Chaoborus and in lakewater. These direct
      relationships support the use of Chaoborus larvae as a Cd biomonitor.

PMID- 11951947
TI  - Effect of initial cell density on the bioavailability and toxicity of copper in
      microalgal bioassays.
AB  - Algal toxicity tests based on growth inhibition over 72 h have been extensively
      used to assess the toxicity of contaminants in natural waters. However, these
      laboratory tests use high cell densities compared to those found in aquatic
      systems in order to obtain a measurable algal response. The high cell densities
      and test duration can result in changes in chemical speciation, bioavailability,
      and toxicity of contaminants throughout the test. With the recent application of
      flow cytometry to ecotoxicology, it is now possible to use lower initial cell
      densities to minimize chemical speciation changes. The speciation and toxicity of
      copper in static bioassays with the tropical freshwater alga Chlorella sp. and
      the temperate species Selenastrum capricornutum (Pseudokirchneriella subcapitata)
      were investigated at a range of initial cell densities (10(2)-10(5) cells/ml).
      Copper toxicity decreased with increasing initial cell density. Copper
      concentrations required to inhibit growth (cell division) rate by 50% (72-h
      median effective concentration [EC50]) increased from 4.6 to 16 microg/L for
      Chlorella sp. and from 6.6 to 17 microg/L for S. capricornutum as the initial
      cell density increased from 10(2) to 10(5) cells/ml. Measurements of anodic
      stripping voltammetry-labile, extracellular, and intracellular copper confirmed
      that at higher initial cell densities, less copper was bound to the cells,
      resulting in less copper uptake and lower toxicity. Chemical measurements
      indicated that reduced copper toxicity was due primarily to depletion of
      dissolved copper in solution, with solution speciation changes due to algal
      exudates and pH playing a minor role. These findings suggest that standard static
      laboratory bioassays using 10(4) to 10(5) algal cells/ml may seriously
      underestimate metal toxicity in natural waters.

PMID- 11951948
TI  - Effects of contact time on the sequestration and bioavailability of different
      classes of hydrophobic organic chemicals to benthic oligochaetes (Tubificidae).
AB  - Differences in bioavailability of hydrophobic organic compounds (HOC) to benthic
      deposit feeders have been related to differences in sediment-HOC contact time and
      sequestration (formation of slowly desorbing fractions) status. As a consequence,
      it was postulated that contact time and/or sequestration should be incorporated
      into risk assessment. In the present study, we investigated the effect of contact
      time on the bioavailability and sequestration of different classes of HOC. For
      this purpose, we simultaneously measured the steady-state accumulation into
      benthic oligochaetes (Tubificidae) and the distribution over rapidly and slowly
      desorbing fractions in laboratory-contaminated sediment at different contact
      times. The decrease in rapidly desorbing fractions (Frap) of polychlorinated
      biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and 2,2-bis (4
      chlorophenyl)-1,1-dichloroethylene (p,p'-DDE) after a contact time of 959 d did
      not exceed a factor of 1.2. Similarly, the reduction in bioavailability was a
      factor of 2.3 at maximum, indicating that long contact times do not necessarily
      result in pronounced bioavailability reduction. For chlorobenzenes, the
      bioavailability was reduced with a factor of 5 to 18. This decrease corresponded
      with a pronounced reduction in Frap, which was attributed to losses of rapidly
      desorbing compounds. Over 75% of the variation in biota-to-sediment accumulation
      factors (BSAFs) of the PAHs and chlorobenzenes at the three contact times could
      be explained by differences in Frap. The present study provides evidence of a
      relationship between sequestration status and bioavailability of HOC to benthic
      deposit feeders.

PMID- 11951949
TI  - Copper toxicity to larval Mercenaria mercenaria (hard clam).
AB  - Preset larval Mercenaria mercenaria were exposed to nominal concentrations of 1
      (control) to 495 microg Cu/L in artificial seawater and monitored for mortality,
      activity, development, and metamorphosis in sealed 30-mm plastic petri plates
      containing 1.5 ml of artificial seawater or toxicant solution. The plastic petri
      plates sorbed only about 2.6 microg/L at any dose and allowed direct observation
      of larval clams under a light microscope for a period of two weeks; control
      survivorship was in excess of 60% at 400 h. The dose-response curve for mortality
      for clams exposed to copper and fed Isochrysis galbana was characterized by
      survival similar to or better than controls at doses of 5 and 14 microg Cu/L,
      while doses of 7 and > or = 29 microg Cu/L exhibited mortality greater than
      controls. Values of lowest concentration at which 50% of the organisms died
      (LC50) were 62.4, 21.2, and 11.7 microg Cu/L, and the lowest observed adverse
      effect concentration values of 57, 29, and 29 microg Cu/L were determined at 48,
      96, and 192 h, respectively. In contrast, activity, as judged by swimming,
      exhibited a typical exponentially decreasing response at these same
      concentrations. Experiments on the uptake of dissolved copper by I. galbana
      confirmed literature reports that these algae concentrate copper. Ingesting
      copper-containing algae was demonstrated to be a source of copper toxicity for
      larval clams.

PMID- 11951950
TI  - Effects of ethynylestradiol on the reproductive physiology in zebrafish (Danio
      rerio): time dependency and reversibility.
AB  - Environmental pollution with natural or synthetic estrogens may pose a serious
      threat to reproduction of wildlife species. This study describes the effects of
      17-alpha-ethynylestradiol (EE2) on fish reproductive organs in a laboratory
      model. Adult zebrafish were semistatically exposed to nominal concentrations of
      0, 10, and 25 ng/L EE2 for 24 d and then transferred to EE2-free medium.
      Gonadosomatic index (GSI), plasma vitellogenin concentration (VTG), and histology
      of the gonads (control and 10 ng/L only) were examined as a function of time. It
      was found that EE2 has an adverse impact on both male and female reproductive
      organs. Notably in females, gonadal changes were observed through histological
      evaluation after 3 d of exposure to 10 ng/L EE2. and this was followed by a
      reduction of GSI at day 6 of exposure. In males, a reduction of GSI and altered
      testis histology was found after 24 d of exposure to 10 ng/L. The observed
      effects on the ovary after EE2 exposure, combined with complete recovery after 24
      d, is considered to be triggered by feedback at the level of the pituitary. In
      both males and females, VTG was induced in response to EE2 and normalized during
      the recovery period. The observed correlation between VTG and ovarian somatic
      index (OSI) demonstrates that excessive VTG induction may be predictive for
      adverse effects of EE2 on ovarian function in female zebrafish. These results
      indicate that long-term stimulation by synthetic estrogens such as EE2 might
      impair reproductive function in zebrafish in a reversible manner.

PMID- 11951951
TI  - Toxicity testing using esterase inhibition as a biomarker in three species of the
      genus Lecane (Rotifera).
AB  - We have developed an esterase inhibition test to investigate the effects of 10
      toxicants, including six metals (cadmium, chromium, copper, lead, mercuric
      chloride, and titanium) and four organics (benzene, ethyl acetate, toluene, and
      vinyl acetate) in three species of the benthic rotifer genus Lecane (L. hamata,
      L. luna, and L. quadridentata). Metals affect esterase inhibition by an average
      value of 4,957-fold greater than the four organics tested for the three rotifer
      species. Most of the EC50 (effect concentration where a 50% reduction in esterase
      activity is observed) values correspond to environmentally realistic
      concentrations. Comparisons of acute-to-chronic ratios among these three species
      showed that in two species, L. luna and L. quadridentata, esterase inhibition is
      an outstanding biomarker for most of the toxicants tested.

PMID- 11951952
TI  - Xenoestrogenic gene expression: structural features of active polycyclic aromatic
      hydrocarbons.
AB  - Estrogenicity was assessed using the Saccharomyces cerevisiae-based Lac-Z
      reporter assay and was reported as the logarithm of the inverse of the 50% molar
      beta-galactosidase activity (log[EC50(-1)]). In an effort to quantify the
      relationship between molecular structure of polycyclic aromatic hydrocarbons
      (PAHs) and estrogenic gene expression, a series of PAHs were evaluated. With
      noted exceptions, the results of these studies indicate that the initial two
      dimensional structural warning for estrogenicity, the superpositioning of a
      hydroxylated aromatic system on the phenolic A-ring of 17-beta-estradiol, can be
      extended to the PAHs. This two-dimensional-alignment criterion correctly
      identified estrogenicity of 22 of the 29 PAHs evaluated. Moreover, the estrogenic
      potency of these compounds was directly related to the size of the hydrophobic
      backbone. The seven compounds classified incorrectly by this structural feature
      were either dihydroxylated naphthalenes or aromatic nitrogen-heterocyclic
      compounds; all such compounds were false positives. Results with dihydroxylated
      naphthalenes reveal derivatives that were nonestrogenic when superimposed on the
      phenolic A-ring of 17-beta-estradiol had the second hydroxyl group in the
      position of the C-ring or were catechol-like in structure. Structural alerts for
      nitrogen-heterocyclic compounds must take into account the position of the
      hydroxyl group and the in-ring nitrogen atom; compounds with the hydroxyl group
      and nitrogen atom involved with the same ring were observed to be nonactive.

PMID- 11951953
TI  - The chemical toxic benzo[a]pyrene perturbs the physical organization of
      phosphatidylcholine membranes.
AB  - The interaction of the chemical carcinogen benzo[a]pyrene (BaP) with
      phosphatidylcholine membranes has been investigated by using various physical
      techniques. Differential scanning calorimetry showed that BaP, at concentrations
      as low as 2 mol% in mixtures with dimyristoylphosphatidylcholine (DMPC),
      dipalmitoylphosphatidylcholine, and distearoylphosphatidylcholine, abolished the
      pretransition and broadened and shifted to lower temperatures the main gel-to
      liquid crystalline phase transition. The effect was stronger as the lipid acyl
      chain length decreased. Infrared spectroscopy indicated that inclusion of BaP had
      a strong influence on the carbonyl (C=O) stretching band. Fitting of this band
      resulted in the presence of three components in the case of samples containing
      BaP, centered at 1,742, 1,727, and 1,704 cm(-1) (only two components, at 1,742
      and 1,727 cm(-1), were observed for pure DMPC). The component at 1,704 cm(-1)
      corresponded to a disolvate and strongly supported the notion that inclusion of
      BaP increases hydration of the bilayer C=O. Small-angle x-ray diffraction showed
      that incorporation of 10 mol% BaP into DMPC increased bilayer thickness from 66.7
      to 71 A in the gel state and from 58.9 to 60.9 A in the fluid phase. It is
      proposed that, when BaP is incorporated into a phospholipid bilayer, it locates
      in the most apolar region of the phospholipid palisade, resulting in expansion
      and swelling of the membrane. These two effects will facilitate water penetration
      into the polar region of the membrane, as observed by the increased hydration of
      the C=O groups, and thus perturb both membrane integrity and functionality.

PMID- 11951954
TI  - Hepatic microsomal cytochrome p450s and chlorinated hydrocarbons in largha and
      ribbon seals from Hokkaido, Japan: differential response of seal species to Ah
      receptor agonist exposure.
AB  - From 16 largha seals (Phoca largha) and 15 ribbon seals (Phoca fasciata) in the
      coastal waters of Hokkaido, Japan, blubber chlorinated hydrocarbon (CHC) levels
      and hepatic cytochrome P450 (CYP) catalytic activities and their immunochemically
      detected protein content levels were measured. Concentrations of DDTs (2,2-bis(4
      chlorophenyl)-1,1-dichloroethylene,p,p'-DDE; 2,2-bis(4-chlorophenyl)-1,1
      dichloroethane, p,p'-DDD; dichlorodiphenyltrichloroethane, p,p'-DDT),
      polychlorinated biphenyl congeners (PCBs), and chlordane compounds (oxychlordane,
      chlordanes, and nonachlors) in both species were in the range of 290 to 5,300,
      420 to 4,000, and 130 to 1,500 ng/g lipid weight, respectively. Aryl hydrocarbon
      receptor (AhR) agonists, non-ortho (IUPAC 77 and 126) and mono-ortho (IUPAC 105,
      118, and 156) coplanar PCB congeners, were also detected, and the 2,3,7,8
      tetrachlordibenzo-p-dioxin (TCDD) toxic equivalents (TEQs) were 4.9 to 120 pg
      TEQ/g lipid weight. Cross-reactive proteins with polyclonal antibodies against
      rat CYP1A1 and CYP3A2 were notably detected in seal liver microsomes.
      Interestingly, a polyclonal antibody against rat CYP2B1 recognized proteins only
      at trace levels. In largha seals, both levels of alkoxyresorufin- (methoxy-,
      ethoxy-, pentoxy-, and benzyloxyresorufin) O-dealkylase (AROD) activities and
      proteins detected by polyclonal antibodies against rat CYP1A1 were significantly
      correlated with the concentrations of individual coplanar PCB congeners, total
      TEQs, and total PCBs. Threshold concentrations for TEQs in blubber of the largha
      seal to induce hepatic CYP1A protein and EROD activity were estimated to be 8.5
      and 19 pg TEQ/g fat weight, respectively. In ribbon seals, similar correlations
      were not detected, although the TEQ levels were not significantly lower than
      those in largha seals. These results suggest that AROD activity and CYP1A1
      protein in the liver of the largha seal could be a biomarker for the exposure to
      AhR agonists such as coplanar PCB congeners. This study also indicates
      differences in AhR-mediated responses to the CHC exposures between largha and
      ribbon seals.

PMID- 11951955
TI  - Effects of larval exposure to triphenyltin on the survival, growth, and behavior
      of larval and juvenile Ambystoma barbouri salamanders.
AB  - We exposed 10 sibships of the streamside salamander, Ambystoma barbouri, to two
      concentrations of triphenyltin (TPT) (1 and 5 microg/L) and an acetone carrier
      control for the entirety of the larval period. We measured effects on larval
      feeding rates, escape behavior, growth rates, and survival to, days to, and size
      at metamorphosis. Postmetamorphosis, we monitored feeding rates, growth rates,
      and survival of juvenile A. barbouri in order to investigate carryover effects.
      The 5-microg/L TPT concentration resulted in 93% mortality of the larvae.
      Exposure to 1 microg/L TPT had no mortality effect and no effect on the escape
      behavior of larvae. However, larvae exposed to this TPT concentration had
      significantly lower feeding rates and growth rates and therefore metamorphosed
      later than the controls but at the same mass. We detected a direct effect of TPT
      on growth rates beyond the effect through depressed feeding rates. We also found
      significant evidence for variation among sibships in their sensitivity to TPT
      toxicity. Once exposure was terminated at metamorphosis. we observed no residual
      effects of TPT on juveniles. Survival, feeding, and growth rates of juveniles
      exposed to TPT as larvae were not significantly different from those exposed only
      to the acetone carrier.

PMID- 11951956
TI  - Sensitivity of an infaunal amphipod, Eohaustorius estuarius, to acute waterborne
      exposures of 4-nonylphenol: evidence of a toxic hangover.
AB  - Three independent trials were conducted using mortality and burial as endpoints.
      Amphipod mean lethal concentration to 50% (LC50) was 227 microg/L. One-hour
      burial as a sublethal endpoint increased the sensitivity of the toxicity test by
      40%; however, most amphipods that survived exposure were able to recover within
      24 to 48 h. This toxic hangover was dose-dependent.

PMID- 11951957
TI  - Methods for toxicity assessment of contaminated soil by oral or dermal uptake in
      land snails: metal bioavailability and bioaccumulation.
AB  - Using two biological characteristics of the land snail (subspecies Helix aspersa
      aspersa and Helix aspersa maxima), i.e., soil eating and crawling on wet
      surfaces, methods were developed to assess the bioavailability of heavy metals
      (Cd, Cr, Pb, and Zn) from soil and aqueous leachates of soil. Measurement of
      heavy-metal concentrations in soil, leachates, and soft tissues of snails showed
      that contamination from ingested soil is the major route for metal uptake.
      Generally, the concentrations of metals were greater in the viscera than in the
      foot and rose with the proportion of spiked soil (Sl) in the diet. After
      ingestion of soil, bioaccumulation factors in the viscera were over two for Cd
      (3.5-27) and Zn (1.7-4.4) for both subspecies but were below one for Cr (0.04
      0.6, except for H. aspersa maxima: 1.21) and Pb (0.02-0.23). Contamination by
      leachate Sl mainly caused accumulation of Cr in the tissues. Determining the
      metal burden per snail enables an estimation to be made of the risk of secondary
      poisoning encountered by predators. The present study provides data on the
      bioavailability of metals in soils and on the relationships between
      bioaccumulation and sublethal effects.

PMID- 11951958
TI  - Effects of dinoseb on the life cycle of Daphnia magna: modeling survival time and
      a proposal for an alternative to the no-observed-effect concentration.
AB  - Risk assessment is in urgent need of more accurate toxic effect endpoints than
      those currently in use, especially for low concentrations. Often such endpoints
      are estimated by analysis of variance, linear interpolation, or smoothing. As
      these statistical methods are not always satisfactory, some authors have proposed
      to describe the entire dose-response curves by fully formalized parametric
      regression models whose parameters have toxicological meaning. These models allow
      a better evaluation of pollutant effects, including inter- and extrapolation to
      any other than the measured effect values. Following this line, a four-parameter
      logistic regression model (standard model) was fitted to survival data of Daphnia
      magna under pesticide (dinoseb) stress. The heterogeneity of the variance was
      taken into account with a both-sides logarithmic transformation. Besides the
      standard model, a hormesis and a threshold model were tested too. These two
      others models have been described in the literature and might better represent
      the dose-response function we are looking for. All three models showed a good fit
      to our data, and the statistics gave no hints as to which model is the most
      appropriate. As no evidence was seen for hormesis or for the existence of a
      threshold concentration, we used the simplest, namely, the standard model, for
      most of our calculations. Model calculations allow the quantification of the
      effects on individuals' longevity as well as on mean survival time of the
      population. We used them to define a no-effect value, the statistical-no-effect
      concentration (SNEC). The SNEC is based on the confidence bands of the modeled
      regression and represents the highest value for which an effect is statistically
      not different from the control. The SNEC is an alternative to classical
      endpoints, like the no-observed-effect concentration (NOEC) or the low-effect
      concentrations (e.g., EC10, EC5, EC1).

PMID- 11951959
TI  - Characteristics of trophic transfer of polychlorinated biphenyls in marine
      organisms in Incheon North Harbor, Korea.
AB  - The trophic transfer of polychlorinated biphenyls (PCBs) was characterized for
      zooplankton (primarily Paracalanus spp. and Acartia spp.), pacific oyster
      (Crassostrea gigas), shore crab (Hemigrapsus penicillatus), and goby
      (Acanthogobius hasta) in the aquatic system of Incheon North Harbor, Korea. The
      congener pattern in the species was clearly divided by the main PCB uptake route.
      Compared with zooplankton and oyster, the fraction of heavier homologues
      increased in crab and goby that take PCBs from food. Linear relationships were
      observed between log (fugacity in lipid/fugacity in seawater) and log Kow for all
      the species. For zooplankton and oyster, such an observation should not be
      regarded as a true absence of superhydrophobicity, because establishment of
      equilibrium with seawater was not evident. For crab and goby, the absence of
      superhydrophobicity was evidenced by the trophic transfer factor that
      continuously increased with Kow up to 10(7.8). These results suggest that
      superhydrophobicity might be species specific. The trophic transfer factors and
      the fugacity levels in the lipid phase indicated that bioaccumulation in crab and
      goby advanced beyond the level in equilibrium with seawater in the harbor basin.

PMID- 11951960
TI  - Accumulation patterns of polychlorinated biphenyl congeners and organochlorine
      pesticides in Steller's sea eagles and white-tailed sea eagles, threatened
      species, in Hokkaido, Japan.
AB  - Polychlorinated biphenyls (PCBs), including coplanar congeners,
      hexachlorocyclohexane isomers, chlordane-related compounds, and
      hexachlorobenzene, were found in the breast muscle of Steller's sea eagles (SSE)
      and white-tailed sea eagles (WSE) threatened species, collected in Hokkaido,
      Japan, during the two years from 1998 to 1999. Both PCBs and DDTs were the most
      notable compounds, with concentrations one to two orders of magnitude higher than
      the other compounds, that is, from 120 to 39,000 and from 68 to 15,000 ng/g wet
      weight, respectively. Non-ortho (International Union of Pure and Applied
      Chemistry [IUPAC] 77, 126, and 169) and mono-ortho (IUPAC 105, 118, and 156)
      substituted coplanar PCB congeners amounted to 9.2 to 740 pg/g of 2,3,7,8
      tetrachlorodibenzo-p-dioxin toxic equivalents derived from the World Health
      Organization, Paris, France (WHO), toxic equivalent factors. The atmospheric PCBs
      and DDTs in eastern Siberian cities, such as Khabarovsk and Magadan, have been
      reported to be much higher than Hokkaido and the North Pacific. Thus, we
      speculated that the eagles might have been contaminated in these areas, where
      they spend most of the year except winter, which they spend in eastern Siberia.
      Adult eagles accumulated more PCBs and DDTs than younger ones. The patterns of
      PCB congeners were also found to change, depending on the age of the eagle
      examined; adult eagles showed relatively higher proportions of highly chlorinated
      PCBs thanjuvenile eagles did. This difference would be related to the efficiency
      of the excretion and the metabolism of each PCB congener in the eagles.

PMID- 11951961
TI  - Changes in the potential quantum yield of photosystem II and the integrity of
      cell membranes relative to the elemental content of the epilithic desert lichen
      Ramalina maciformis.
AB  - The present study used the epilithic fruticose lichen Ramalina maciformis to
      investigate the occurrence of mineral elements, including heavy metals, at a
      distance of up to 50 km from the industrial region in Ramat Hovav in the Negev
      Desert, Israel. The major objective of this study was an analytical comparison of
      elemental content and physiological parameters of lichen vitality, apart from a
      test of the applicability of this specific lichen in investigations of air
      pollution. The Ca, Cr, Cu, K, Mg, Na, Pb, S, Sr, and Zn content of thalli from
      the unpolluted Tellalim site collected in August 1997, transferred to 24
      biomonitoring sites, and retrieved in April 1998 was analyzed in comparison with
      the following parameters: The potential quantum yield of photosystem 11 (PSII),
      and the integrity of cell membranes. Transplanted thalli in several sites at
      Ramat Hovav accumulated large amounts of most of the elements. The K content of
      the transplants located in the polluted sites indicated a leakage of this
      element, because this content was lower than that of thalli in unpolluted sites.
      Calcium, Cu, Mn, and Na showed an inverse correlation with the K content of the
      lichen. Calcium, Cu, and Sr showed an inverse correlation with the Fv/Fm ratio
      expressing the potential quantum yield of PSII. Calcium, Cr, Cu, Mg, Na, S, and
      Sr showed a positive correlation with the electrical conductivity corresponding
      with cell-membrane disintegration. The present study demonstrated a meaningful
      connection between enlarged concentrations of certain elements and physiological
      phenomena. The capability of the lichen to detect air pollution was found to be
      satisfactory. The dispersion of airborne heavy metals was found, however, to be
      local and limited to a few hundred meters from the source of pollution.

PMID- 11951962
TI  - Toxicity of tributyltin and triphenyltin to early life-stages of Paracentrotus
      lividus (Echinodermata: Echinoidea).
AB  - Sperm cell and embryo toxicity tests using the Mediterranean sea urchin
      Paracentrotus lividus were performed to assess the toxicity of tributyltin
      chloride, bis(tributyltin)oxide, triphenyltin acetate, and triphenyltin
      hydroxide. Toxicity values (mean effective concentration [EC50]) ranged from 2.97
      to 18.5 microg/L for sperm cells and from 1.11 to 2.62 microg/L for embryos. For
      sperm cells, the toxicity of the two tributyl compounds was significantly greater
      than that of two triphenyl compounds; for embryos, the triphenyl compounds
      appeared to be more toxic. Study of embryotoxic effects highlighted closely
      concentration-dependent damages, the most sensitive stages corresponding to the
      crucial phases of differentiation (gastrula and prisma). Both EC50 and no
      observed-effect concentration values for the four organotin compounds are similar
      to those reported in the literature for early life stages of other marine
      organisms.

PMID- 11951963
TI  - Evaluating the ecological significance of laboratory response data to predict
      population-level effects for the estruarine amphipod Ampelisca abdita.
AB  - Ten-day acute mortality of the benthic amphipod Ampelisca abdita is used in a
      number of regulatory, research, and monitoring programs to evaluate chemical
      contamination of marine sediments. Although this endpoint has proven to be
      valuable for characterizing the relative toxicities of sediments, the
      significance of acute mortality with respect to population viability has not yet
      been established. In this study, population modeling along with empirical
      extrapolation were used to describe a relationship between acute mortality and
      population-level response of A. abdita. The research involved the performance of
      a standard 10-d sediment toxicity bioassay and a 70-d full life-cycle chronic
      population (including reproduction) bioassay exposing A. abdita to sediments
      spiked with concentrations of the divalent metal cadmium (normalized to acid
      volatile sulfide) expected to produce a range of biological effects. These data
      provided age-specific schedules of survival and fecundity that were used to
      parameterize an age-classified projection matrix model for A. abdita. Measured
      exposure data and population growth rate estimates, obtained using the
      demographic information collected during the 70-d assay, were used to develop
      exposure-response models. These data were also used to develop an empirical
      relationship between population growth rate (lambda) and acute mortality. This
      relationship describes how acute data may be used to predict concentrations that
      produce population-level effects. Model manipulations permit extrapolation of
      early life-stage mortality (the acute endpoint) to changes in population growth
      rate. These relationships were used to evaluate a range of ecologically
      acceptable acute mortality for A. abdita.

PMID- 11951964
TI  - A Levy flight-random walk model for bioturbation.
AB  - Levy flights are employed in a lattice model of contaminant migration by
      bioturbation, the reworking of sediment by benthic organisms. The model couples
      burrowing, foraging, and conveyor-belt feeding with molecular diffusion. The
      model correctly predicts a square-root dependence on bioturbation rates over a
      wide range of biomass densities. The model is used to predict the effect of
      bioturbation on the redistribution of contaminants in laboratory microcosms
      containing pyrene-inoculated sediments and the tubificid oligochaete Limnodrilus
      hoffmeisteri. The model predicts the dynamic flux from the sediment and in-bed
      concentration profiles that are consistent with observations. The sensitivity of
      flux and concentration profiles to the specific mechanisms of bioturbation are
      explored with the model. The flux of pyrene to the overlying water was largely
      controlled by the simulated foraging activities.

PMID- 11951965
TI  - Comparison of deterministic and probabilistic calculation of ecological soil
      screening levels.
AB  - The U.S. Environmental Protection Agency (U.S. EPA) is sponsoring development of
      ecological soil screening levels (Eco-SSLs) for terrestrial wildlife. These are
      intended to be used to identify chemicals of potential ecological concern at
      Superfund sites. Ecological soil screening levels represent concentrations of
      contaminants in soils that are believed to be protective of ecological receptors.
      An exposure model, based on soil- and food-ingestion rates and the relationship
      between the concentrations of contaminants in soil and food, has been developed
      for estimation of wildlife Eco-SSLs. It is important to understand how
      conservative and protective these values are, how parameterization of the model
      influences the resulting Eco-SSL, and how the treatment of uncertainty impacts
      results. The Eco-SSLs were calculated for meadow voles (Microtus pennsylvanicus)
      and northern short-tailed shrews (Blarina brevicauda) for lead and DDT using
      deterministic and probabilistic methods. Conclusions obtained include that use of
      central-tendency point estimates may result in hazard quotients much larger than
      one; that a Monte Carlo approach also leads to hazard quotients that can be
      substantially larger than one; that, if no hazard quotients larger than one are
      allowed, any probabilistic approach is identical to a worst-case approach; and
      that an improvement in the quality and amount of data is necessary to increase
      confidence that Eco-SSLs are protective at their intended levels of conservatism.

PMID- 11951966
TI  - Characterization of the P13 membrane protein of Borrelia burgdorferi by mass
      spectrometry.
AB  - Borrelia burgdorferi sensu lato is a tick-borne pathogen that causes Lyme
      disease. The characterization of membrane proteins from this and other pathogens
      may yield a better understanding of the mechanisms of infection and information
      useful for vaccine design. Characterization of the highly hydrophobic Borrelia
      outer membrane component P13 from a mutant (OspA- OspB- OspC- and OspD-) strain
      was undertaken by use of a combination of mass spectrometric methods. In a
      previous investigation, an electrospray ionization (ESI) mass spectrum of the
      intact protein provided an average molecular weight that was 20 Da lower than the
      predicted molecular weight. The mass deviation could be explained by a
      modification of the N-terminus of the protein such as pyroglutamylation (-17 Da)
      in combination with the experimental error of measurement, however more
      information was required. New structural information for this membrane protein
      was provided by peptide mapping with matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI TOF MS) and sequencing with ESI
      quadrupole-TOF tandem MS.

PMID- 11951967
TI  - Investigation of drift gas selectivity in high resolution ion mobility
      spectrometry with mass spectrometry detection.
AB  - Recent studies in electrospray ionization (ESI)/ion mobility spectrometry (IMS)
      have focussed on employing different drift gases to alter separation efficiency
      for some molecules. This study investigates four structurally similar classes of
      molecules (cocaine and metabolites, amphetamines, benzodiazepines, and small
      peptides) to determine the effect of structure on relative mobility changes in
      four drift gases (helium, nitrogen, argon, carbon dioxide). Collision cross
      sections were plotted against drift gas polarizability and a linear relationship
      was found for the nineteen compounds evaluated in the study. Based on the reduced
      mobility database, all nineteen compounds could be separated in one of the four
      drift gases, however, the drift gas that provided optimal separation was specific
      for the two compounds.

PMID- 11951968
TI  - In-source H/D exchange and ion-molecule reactions using matrix assisted laser
      desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry
      with pulsed collision and reaction gases.
AB  - Controlled in-source ion-molecule reactions are performed for the first time in
      an external matrix assisted laser desorption ionization (MALDI) source of a
      Fourier transform ion cyclotron resonance mass spectrometer. The MALDI source
      with a hexapole ion guide that was originally designed to incorporate pulsed gas
      to collisionally cool ions (Baykut, G.; Jertz, R.; Witt, M. Rapid Commun. Mass
      Spectrom. 2000, 14, 1238-1247) has been modified to allow the study of in-source
      ion-molecule reactions. Upon laser desorption, a reaction gas was introduced
      through a second inlet and allowed to interact with the MALDI-generated ions
      trapped in the hexapole ion guide. Performing ion-molecule reactions in the high
      pressure range of the ion source prior to analysis in the ion cyclotron resonance
      (ICR) cell allows to maintain the ultra high vacuum in the cell which is crucial
      for high mass resolution measurements. In addition, due to the reaction gas
      pressure in the hexapole product ion formation is much faster than would be
      otherwise possible in the ICR cell. H/D exchange reactions with different
      peptides are investigated, as are proton-bound complex formations. A typical
      experimental sequence would be ion accumulation in the hexapole ion guide from
      multiple laser shots, addition of cooling gas during ion formation, addition of
      reaction gas, varied time delays for the ion-molecule reactions, and transmission
      of the product ions into the ICR cell for mass analysis. In this MALDI source H/D
      exchange reactions for different protonated peptides are investigated, as well as
      proton-bound complex formations with the reaction gas triethylamine. Amino acid
      sequence, structural flexibility and folding state of the peptides can be seen to
      play a part in the reactivity of such ions.

PMID- 11951969
TI  - A general method for precalculation of parameters for sustained off resonance
      irradiation/collision-induced dissociation.
AB  - Sustained off resonance irradiation (SORI) collision-induced dissociation (CID)
      is a commonly used method of collisionally activating ions for fragmentation in
      Fourier transform mass spectrometric experiments. To achieve the degree of
      fragmentation desired, both the irradiation frequency and amplitude must be
      optimized. This is a time-consuming procedure, particularly when the m/z values
      of the precursor ions vary over a broad range. We present an approach that
      simplifies this optimization by precalculating the irradiation frequency of the
      ions to be fragmented as a constant percentage of the reduced cyclotron
      frequency. Using this approach, the optimal amplitude was found to be
      significantly less dependent on the m/z value of the precursor ion, and therefore
      required little or no adjustment. This method considerably simplified
      optimization of SORI-CID for analysis of carbohydrates, glycoconjugates, and
      peptides over the mass range m/z 300-3500, requiring optimization of only a
      single experimental parameter, the irradiation amplitude, and only for the first
      MS/MS stage.

PMID- 11951970
TI  - Evidence for long-range glycosyl transfer reactions in the gas phase.
AB  - A long-range glycosyl transfer reaction was observed in the collision-induced
      dissociation Fourier transform (CID FT) mass spectra of benzylamine-labeled and 9
      aminofluorene-labeled lacto-N-fucopentaose I (LNFP I) and lacto-N-difucohexaose I
      (LNDFH I). The transfer reaction was observed for the protonated molecules but
      not for the sodiated molecules. The long-range glycosyl transfer reaction
      involved preferentially one of the two L-fucose units in labeled LNDFH I. CID
      experiments with labeled LNFP I and labeled LNFP II determined the fucose with
      the greatest propensity for migration. Further experiments were performed to
      determine the final destination of the migrating fucose. Molecular modeling
      supported the experiments and reaction mechanisms are proposed.

PMID- 11951971
TI  - Evaluation of sample preparation techniques for mass measurements of PCR products
      using ESI-FT-ICR mass spectrometry.
AB  - Elimination of PCR buffer components and alkali metal cations (i.e., Na+, K+) is
      of critical importance to allow for accurate mass measurements of PCR products
      for genotyping and sequencing applications. Ethanol precipitation followed by
      microdialysis has been repeatedly shown to efficiently desalt PCR products for
      analysis by mass spectrometry and is considered the gold standard. Alternative
      cleanup techniques that are compatible with automation are explored here with the
      intent of expanding the bottleneck that exists between the production of PCR
      products and analysis by electrospray ionization mass spectrometry (ESI-MS).
      Numerous combinations of approaches were evaluated that included PCR purification
      kits and alcohol precipitations. The data shown here support alternative
      approaches to an ethanol precipitation followed by microdialysis that have
      comparable desalting efficiency and can be utilized for cleanup of PCR products
      generated from single reactions.

PMID- 11951972
TI  - In electrospray ionization source hydrogen/deuterium exchange LC-MS and LC-MS/MS
      for characterization of metabolites.
AB  - A new method is described for performing hydrogen/deuterium (H/D) exchange in an
      electrospray ionization (ESI) source. The use of liquid chromatography (LC)-mass
      spectrometer equipped with an ESI source and deuterium oxide (D2O) as the sheath
      liquid allows H/D exchange experiments to be performed on-line. This directly
      provides information for determining the number and position of exchangeable
      hydrogens, aiding in the elucidation of the structures of drug metabolites. To
      demonstrate the utility of this method, LC-mass spectrometry (MS) and LC-MS/MS
      experiments were performed using either H2O or D2O as sheath liquid on a matrix
      metalloprotease (MMP) inhibitor (PD 0200126) and its metabolites. Examination of
      the mass shift of the deuteriated molecule from that of the protonated molecule
      allowed the number of exchangeable protons to be determined. Interpretation of
      the production-spectra helped to determine the location of the exchanged protons
      and assisted in the assignment of the site(s) of modification for each
      metabolite.

PMID- 11951974
TI  - Differentiation of stereoisomeric steroids by reactions with phosphenium ions.
AB  - A chemical ionization method is reported for distinction of diastereomeric
      hydroxysteroids by using Fourier-transform ion cyclotron mass spectrometry (FT
      ICR). Certain phosphenium ions are demonstrated to react with stereoisomeric
      steroids to yield qualitatively different product ions. For example, 1,3,5(10)
      estratriene-3,16beta,17beta-triol (cis-estriol) reacts with the dimethoxy
      phosphenium ion to form a diagnostic product ion (not formed for the trans
      estriol) through addition followed by the loss of two molecules of methanol. In
      an analogous manner, the 1,3-dioxolan-2-phosphenium ion produces a diagnostic
      product ion through the loss of ethylene glycol from the adduct of cis-estriol
      only. The 1,3,5(10)-estratriene-3,16alpha,17beta-triol (trans-estriol), on the
      other hand, reacts with each phosphenium ion only via hydroxide abstraction
      initiated pathways that indicate the presence of at least two hydroxyl groups in
      the molecule. These specific reactions take place for all hydroxysteroids
      examined, independent of their stereochemistry. Another isomer pair, cholestan
      3alpha,5alpha-diol (cis-cholestandiol) and cholestan-3beta,5alpha-diol (trans
      cholestandiol), is differentiated based on selective elimination of water only
      from the adduct of the cis-isomer. However, the method does not allow distinction
      between the stereoisomeric 5beta-pregnane-3alpha,17alpha,20alpha-triol and 5beta
      pregnane-3alpha,17alpha,20beta-triol. The different reactivities of the three
      pairs of steroid isomers and of each diastereomeric compound pair are
      rationalized by reaction enthalpies and steric effects based on straightforward
      and predictable reaction mechanisms.

PMID- 11951973
TI  - Desorption/ionization of biomolecules from aqueous solutions at atmospheric
      pressure using an infrared laser at 3 microm.
AB  - A new atmospheric pressure (AP) infrared (IR) matrix-assisted laser
      desorption/ionization (MALDI) ion source was developed and interfaced with a
      Thermo Finnigan LCQ ion trap mass spectrometer. The source utilized a miniature
      all-solid-state optical parametric oscillator (OPO)-based IR laser system tunable
      in the lambda = 1.5-4 microm spectral range and a nitrogen ultraviolet (UV) laser
      (lambda = 337 nm) for use in comparative studies. The system demonstrated
      comparable performance at 3 microm and 337 nm wavelengths if UV matrices were
      used. However, AP IR-MALDI using a 3 microm wavelength showed good performance
      with a much broader choice of matrices including glycerol and liquid water. AP IR
      MALDI mass spectra of peptides in the mass range up to 2000 Da were obtained
      directly from aqueous solutions at atmospheric conditions for the first time. A
      potential use of the new AP IR-MALDI ion source includes direct MS analysis of
      biological cells and tissues in a normal atmospheric environment as well as on
      line coupling of mass spectrometers with liquid separation techniques.

PMID- 11951975
TI  - Tandem mass spectrum of a growth hormone secretagogue: amide bond cleavage and
      resultant gas-phase rearrangement.
AB  - Compound 1 [N-[1(R)-[(1,2-dihydro-1-methylsulfonylspiro[3H-indole-3,4'-piperidin]
      1'-yl)carbonyl]-2-(phenylmethyloxy)ethyl]-2-amino-2-methylpropanamide](MW 528) is
      an orally-active growth hormone secretagogue (GHS). As part of a continual effort
      to analyze the ESI/MS and MSn data of novel drugs, the ESI/MS and MS/MS data of
      protonated 1 (m/z 529) are analyzed and reported here. The analyses reveal that
      under low-energy collision-induced dissociation (CID) in an ion trap or a
      quadrupole collision cell, protonated 1 undergoes a gas-phase rearrangement to
      form protonated 3 (m/z 357) which competes with the y- and b-type product ions
      during the amide bond cleavages of protonated 1. It is proposed that when the b
      type ion is formed by cleavage of the piperidine amide bond, piperidine (a
      neutral species) and the b-ion (a cation) form an ion-neutral complex. In this
      complex, piperidine functions as a nucleophile to attack the benzylic carbon of
      the b-ion, and the protonated ether group in the b-ion acts as a leaving group,
      which results in the migration of the benzylic group to the piperidine amine to
      form protonated 3. Protonated 2 (an analog of 1) was studied under the same
      experimental conditions. The results show that protonated 2 undergoes a similar
      rearrangement to form protonated 3. While this rearrangement is a relatively
      minor fragmentation process for protonated 1, it is a predominant process for
      protonated 2. This phenomenon is explained in terms of the proposed ion-neutral
      complex mechanism.

PMID- 11951976
TI  - Qscore: an algorithm for evaluating SEQUEST database search results.
AB  - A scoring procedure is described for measuring the quality of the results for
      protein identifications obtained from spectral matching of MS/MS data using the
      Sequest database search program. The scoring system is essentially probabilistic
      and operates by estimating the probability that a protein identification has come
      about by chance. The probability is based on the number of identified peptides
      from the protein, the total number of identified peptides, and the fraction of
      distinct tryptic peptides from the database that are present in the identified
      protein. The score is not strictly a probability, as it also incorporates
      information about the quality of the individual peptide matches. The result of
      using Qscore on a large test set of data was similar to that achieved using
      approaches that validate individual spectral matches, with only a narrow overlap
      in scores between identified proteins and false positive matches. In direct
      comparison with a published method of evaluating Sequest results, Qscore was able
      to identify an equivalent number of proteins without any identifiable false
      positive assignments. Qscore greatly reduces the number of Sequest protein
      identifications that have to be validated manually.

PMID- 11951977
TI  - Frequency shifts due to the interference of resolved peaks in magnitude-mode
      Fourier-transform ion cyclotron resonance mass spectra.
AB  - We have obtained relationships for frequency shifts resulting from the
      interference of spectral components for the magnitude mode Fourier transform. The
      approximation of a weak perturbation of well resolved peaks has been used. Both
      the low- and high-pressure limits for Fourier-transform ion cyclotron resonance
      (FTICR) operation have been considered. We have found that the shifts can be
      either negative or positive, depending on the initial phase and/or the choice of
      the time-domain interval. The magnitude of shifts generally does not exceed the
      peak width. In the approximation of small perturbations the shifts produced by
      multiple peaks are additive. We have compared theoretical results with
      experimental shifts for isotopic clusters of multiply charged insulin. Up to 1
      ppm frequency variations were experimentally observed for the insulin 5+ charge
      state, consistent with theoretical estimates. The peak interference is of
      particular significance in the case of bio-molecular mass spectra having a large
      number of peaks and covering a considerable dynamic range (i.e., relative
      abundance). We conclude that the common mass measurement procedure based on the
      location of the magnitude mode maxima of well resolved peaks can result in
      systematic mass measurement errors. The relationships obtained provide
      corrections for the frequency shifts and thus improve the mass measurement
      accuracy.

PMID- 11951978
TI  - High pressure matrix-assisted laser desorption/ionization Fourier transform mass
      spectrometry for minimization of ganglioside fragmentation.
AB  - Transiently elevating pressure in a matrix-assisted laser desorption/ionization
      Fourier transform mass spectrometry (MALDI-FTMS) source into the 1-10 mbar range
      during ionization decreases the metastable fragmentation of gangliosides. This
      allows detection of the molecular ion species without loss of the highly labile
      sialic acid residues. In these experiments, gangliosides with up to five sialic
      acids were ionized by MALDI and detected with the FTMS. In each case, when the
      high pressure collisional cooling was used, the singly charged molecular ion was
      the base peak in the spectra, both in the positive and negative ion modes, and
      minimal metastable fragmentation was observed. This result is promising, as the
      previously developed TLC separation methods can be coupled to MALDI-FTMS.

PMID- 11951979
TI  - Gas-phase fragmentation of the Ag+-phenylalanine complex: cation-pi interactions
      and radical cation formation.
AB  - Collision-induced dissociation experiments on the Ag+-phenylalanine complex using
      several collision energies were shown to yield ten different fragment ions.
      Unambiguous assignment of these fragment ions were made by careful analysis of
      deuterium labeling experiments. The losses of H2O, CO, CO2, and AgH were commonly
      observed; also encountered were the losses of H2, Ag, and H. Deuterium labeling
      experiments and density functional calculations have been employed to probe
      fragmentation mechanisms that account for all experimental results.

PMID- 11951980
TI  - Phosphorus fractionation in lake sediments--lakes Volvi and Koronia, N. Greece.
AB  - Sediments from two lakes, the meso-to-eutrophic Volvi and the hypertrophic
      Koronia, located in N. Greece were examined on the basis of P-fractionation. In
      both lakes, the rank order of P-fractions was HCl-P > NaOH-P > BD-P > NH4Cl-P.
      The loosely sorbed phosphorus (NH4Cl-P) represented < 1% of the sedimentary
      inorganic phosphorus, while the reductant phosphorus (BD-P) ranged 5-6%. The
      calcium bound phosphorus (HCl-P) showed considerable contribution (59-74%) to the
      sedimentary inorganic P-loads. The metal oxide bound phosphorus (NaOH-P) was
      higher in the hypertrophic (30-35%) than in the meso-to-eutrophic system (19
      28%). Fine-sized sediments exhibited significantly higher concentrations of HCl-P
      in Volvi and NH4Cl-P in Koronia. Sampling month had significant effect in
      variance of most P-fractions and other sediment features in both lakes. Use was
      also made of multivariate statistics to identify the factors which influence the
      sedimentary phosphorus. NaOH-P was the most reactive fraction in Lake Volvi. Iron
      compounds and organic matter seem to play a significant role in regulating this
      labile P-budget. NH4Cl-P was the more reactive fraction in Lake Koronia which was
      influenced by sedimentation of P-absorbed on clay/silt fine particles.

PMID- 11951981
TI  - Spiking of performance reference compounds in low density polyethylene and
      silicone passive water samplers.
AB  - A method for spiking performance reference compounds (PRCs) into low density
      polyethylene (LDPE) and silicone polymers is described. This method is based on
      equilibration of the polymers in aqueous/methanolic solutions of PRCs.
      Equilibration times range from minutes to hours for perdeuterated polyaromatic
      hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) with a hydrophobicity in
      the range 3.9 < logKow < 7.7. Best results were obtained for methanol-water
      ratios of 80/20 (v/v). The method allows for the use of PRCs for in situ
      calibration of the uptake kinetics of these solvent-free sampling phases in a
      similar way as for semipermeable membrane devices (SPMDs).

PMID- 11951982
TI  - Comparison between fractionation and bioavailability of trace elements in
      rhizosphere and bulk soils.
AB  - Rhizosphere is a microbiosphere and has quite different chemical, physical and
      biological properties from bulk soils. A greenhouse experiment was performed to
      compare the difference of fractionation and bioavailability of trace elements Cr,
      Ni, Zn, Cu, Pb and Cd between rhizosphere soil and bulk soil. In the meantime,
      the influence of air-drying on the fractionation and bioavailability was also
      investigated by using wet soil sample as a control. Soils in a homemade rhizobox
      were divided into four zones: rhizosphere, near rhizosphere, near bulk soil and
      bulk soil zones, which was designated as S1, S2, S3 and S4. Elemental speciations
      were fractionated to water soluble, exchangeable and carbonate bound (B1), Fe-Mn
      oxide bound (B2), and organic and sulfide bound (B3) by a sequential extraction
      procedure. Speciation differences were observed for elements Cr, Ni, Zn, Cu, Pb
      and Cd between the rhizosphere and bulk soils, and between the air-dried and wet
      soils as well. The concentrations of all six heavy metals in fraction B1 followed
      the order of S2 > S3 > S1 > S4 and for B2, the order was S2 > S3 S4 > S1. For B3,
      the order was S1 > S3 S4 > S2, while for Cd the order was S2 > S3 approximately/=
      S4 > S1. The air-drying increased elemental concentration in fractions B1 and B2
      by 20-50% and decreased in fraction B3 by about 20-100%. Correlation analysis
      also indicated that the bioavailability correlation coefficient of fraction B1 in
      rhizosphere wet soil to plants was better than that between either air-dried or
      nonrhizosphere soils. Therefore, application of rhizosphere wet soils should be
      recommended in the future study on the speciation analysis of trace elements in
      soils and bioavailability.

PMID- 11951983
TI  - Solar light induced and TiO2 assisted degradation of textile dye reactive blue 4.
AB  - Aqueous solutions of reactive blue 4 textile dye are totally mineralised when
      irradiated with TiO2 photocatalyst. A solution containing 4 x 10(-4) M dye was
      completely degraded in 24 h irradiation time. The intensity of the solar light
      was measured using Lux meter. The results showed that the dye molecules were
      completely degraded to CO2, SO4(2-), NO3-, NH4+ and H2O under solar irradiation.
      The addition of hydrogen peroxide and potassium persulphate influenced the
      photodegradation efficiency. The rapidity of photodegradation of dye
      intermediates were observed in the presence of hydrogen peroxide than in its
      absence. The auxiliary chemicals such as sodium carbonate and sodium chloride
      substantially affected the photodegradation efficiency. High performance liquid
      chromatography and chemical oxygen demand were used to study the mineralisation
      and degradation of the dye respectively. It is concluded that solar light induced
      degradation of textile dye in wastewater is a viable technique for wastewater
      treatment.

PMID- 11951984
TI  - Photodegradation of the herbicide EPTC and the safener dichlormid, alone and in
      combination.
AB  - Photodegradation of the herbicide EPTC (S-ethyl-N, N-dipropylthiocarbamate), and
      the safener dichlormid (2,2-dichloro-N, N-diallylacetamide) has been examined in
      methanol and in water solutions. Irradiation of EPTC and dichlormid with UV light
      at 254 nm caused rapid degradation in both media. Remarkable and gradual changes
      in color of EPTC irradiated solution was observed from clear to yellow then to
      intense orange. EPTC half-life of elimination in water was 14.0, and 18.5 min,
      and in methanol 37.2 and 32.2 min, when irradiated with and without dichlormid,
      respectively. There was significant difference between rate of EPTC degradation
      in water and methanol in the presence or in the absence of dichlormid. Negligible
      degradation of EPTC or dichlormid at > 290 nm was observed. Photoproducts were
      separated and identified using GC or/and thin-layer chromatography then
      identified using mass spectrometry. It appeared that some products have high
      molecular weight that formed as a result of dimerization. This is possibly a
      result of the coupling of radicals that formed through EPTC degradation. The
      cleavage of C-S and C-N bonds accounted for the formation of these radicals.
      Gradual dealkylation of the acid chains of EPTC has also occurred. EPTC
      sulfoxide, EPTC-sulfone, Propylamine and dipropylamine were detected as
      photoproducts of EPTC at 254 nm. Dichlormid pathways of degradation at 254 nm
      were characterized as dechlorination, dealkylation, and hydrolysis both in water
      and methanol. The findings showed that dichlormid did not significantly affect
      EPTC photodegradation either at 254 nm or at > 290 nm. The
      biological/toxicological properties of the photoproducts need further study,
      particularly the dimer compounds.

PMID- 11951985
TI  - Phototransformation of polychlorinated dibenzo-p-dioxins from photolysis of
      pentachlorophenol on soils surface.
AB  - The phototransformation of polychlorinated dibenzo-p-dioxins (PCDDs) by
      photolysis of pentachlorophenol (PCP) on soil surface under irradiation of UV
      light in the laboratory has been investigated. Octachlorodibenzo-p-dioxin (OCDD)
      and heptachlorodibenzo-p-dioxin (H7CDD) were detected from the products of the
      photoreactions. The effects of soil types with different basic soil
      physicochemical properties were varied from silt loam, silt clay and clay soil on
      the formation of PCDDs by irradiation of PCP on soils surface. Fulvic acids can
      prevent phototransformation of PCDDs by photolysis of PCP on soil surface.

PMID- 11951986
TI  - Determination of malic acid and other C4 dicarboxylic acids in atmospheric
      aerosol samples.
AB  - An ion chromatographic method was developed which is able to separate five
      unsubstituted and hydroxy C4 dicarboxylic acids, succinic, malic, tartaric,
      maleic and fumaric acid, besides the other unsubstituted C2-C5 dicarboxylic
      acids, oxalic, malonic and glutaric acids, as well as inorganic ions in samples
      extracted from atmospheric particulate matter. By the application of this method
      it was found for both rural and urban sites and for various types of air masses
      that in the summer-time malic acid is the most prominent C4 diacid (64 ng m(-3)
      by average), exceeding succinic acid concentration (28 ng m(-3) by average)
      considerably. In winter-time considerably less, a factor of 4-15, C4 acids
      occurred and succinic acid was more concentrated than malic acid. Tartaric,
      fumaric and maleic acids were less concentrated (5.1, 5.0 and 4.5 ng m(-3) by
      average, respectively). Tartaric acid was observed for the first time in ambient
      air. The results indicate that in particular anthropogenic sources are important
      for the precursors of succinic, maleic and fumaric acids. Biogenic sources seem
      to influence the occurrence of malic acid significantly.

PMID- 11951987
TI  - Ice (photo)chemistry. Ice as a medium for long-term (photo)chemical
      transformations--environmental implications.
AB  - This review accounts for the current knowledge about the distribution,
      accumulation, and chemical/photochemical transformations of persistent,
      bioaccumulative, and toxic compounds (PBTs) in water ice, especially in the
      connection with polar regions and atmospheric cloud particles. (Photo)reactions
      on/in ice are discussed in terms of photochemistry, photobiology, paleochemistry,
      as well as astrophysics. Authors propose a model, in which a significant amount
      of some PBTs are generated by (photo)chemistry of primary pollutants in ice,
      which may subsequently be released to the environment. It is argued that ice
      photochemistry might play an important role in the chemical transformations in
      cold ecosystems and in the upper atmosphere, particularly now when the ozone
      layer is partially depleted.

PMID- 11951988
TI  - Thermodynamics of binding of cadmium to bovine serum albumin.
AB  - The binding isotherm of Cd2+ ion to bovine serum albumin (BSA) has been
      investigated by microcalorimetry at 310.15 K and pH 7.0. The thermodynamic
      parameters of the binding reaction have been determined, and the stoichiometry of
      the complex is 2:1, indicating that there exist two identical binding sites of
      BSA with Cd2+ ion. The value of deltarHthetam is -28.4+/-1.7 kJ mol(-1), the free
      energy of binding deltarGthetam is -25.2 kJ mol(-1), and the entropy of binding
      deltarSthetam is -10.3 J mol(-1) K(-1). The negative deltarHthetam and
      deltarSthetam values are observed for the binding reaction of Cd2+ ion and BSA,
      suggesting that the binding reaction is mainly enthalpy-driven and the entropy is
      unfavorable for it.

PMID- 11951989
TI  - Chlorination of bisphenol A in aqueous media: formation of chlorinated bisphenol
      A congeners and degradation to chlorinated phenolic compounds.
AB  - The chlorination of bisphenol A (BPA) in aqueous media was investigated in order
      to describe the degradation profile of this compound and the formation of
      chlorinated products. Aqueous solutions of BPA (approx. 1 mg/l) were chlorinated
      by sodium hypochlorite solution at room temperature and under weakly alkaline
      conditions. Chlorinated compounds were extracted with dichloromethane and
      determined by gas chromatography/mass spectrometry (GC/MS). BPA was consumed
      completely within 5 min of chlorination, when the initial chlorine concentration
      was 10.24 mg/l (molar ratio to BPA, 58.7). On the other hand, when the initial
      chlorine concentration was 1.03 mg/l (molar ratio, 6.56), 9.3% of BPA still
      remained after 60 min chlorination. Five chlorinated BPA congeners, 2
      chlorobisphenol A (MCBPA), 2,6-dichlorobisphenol A (2,6-D2CBPA), 2,2'
      dichlorobisphenol A (2,2'-D2CBPA), 2,2',6-trichlorobisphenol A (T3CBPA) and 2,2',
      6,6'-tetrachlorobisphenol A (T4CBPA) were formed in the earlier stages of
      chlorination. Several chlorinated phenolic compounds, 2,4,6-trichlorophenol
      (T3CP), 2,6-dichloro-1,4-benzoquinone (D2CBQ), 2,6-dichloro-1,4-hydroquinone
      (D2CHQ), C9H10Cl2O2, C9H8Cl2O and C10H12Cl2O2, were also formed by further
      chlorination.

PMID- 11951990
TI  - Black carbon in Slovenian alpine lacustrine sediments.
AB  - Black carbon (BC) contents were measured in recent sediments in five high
      altitude remote alpine lakes, i.e. Lake Krisko Sup., Lake Ledvica, Lake Planina,
      Lake Krn and Lovrensko Lake, and the eutrophic subalpine Lake Bled in Slovenia to
      follow the history of atmospheric pollution of fossil fuel and local biomass
      burning in Alps. Organic carbon (OC), its 13C values, total nitrogen and
      sedimentation rates using 210Pb activity data were also measured. The highest BC
      contents, reaching 20 mg/gdw, were noted in remote alpine lakes while in the
      subalpine Lake Bled sediment the concentrations were lower reaching 5 mg/gdw.
      Lower BC/OC ratios, ranging between 4% and 8%, were typical for remote alpine
      lakes and increased to about 10% in subalpine Lake Bled. The latter clearly shows
      the marked importance of local direct pollution sources in comparison to remote
      atmospheric input which decreases in a W-E direction in parallel with decreasing
      amounts of precipitation. Based on 210Pb sedimentation data, the minimal BC
      accumulation rates in sediment cores were detected in the pre-industrialisation
      period. In the last decades of 20th century the BC contents decreased probably
      due to reduced emission of pollutants.

PMID- 11951991
TI  - The estimation of PAH bioavailability in contaminated sediments using
      hydroxypropyl-beta-cyclodextrin and Triton X-100 extraction techniques.
AB  - A study was conducted to investigate whether cyclodextrins and surfactants can be
      used to predict polycyclic aromatic hydrocarbon (PAH) bioavailability in
      contaminated sediments. Two sediment samples were extracted with aqueous
      solutions of hydroxypropyl-beta-cyclodextrin (HPCD) and Triton X-100. PAH removal
      during extraction was compared with PAH removal during biodegradation and solid
      phase extraction. The latter two methods were used as reference methods to
      establish which part of the PAHs could be biodegraded and to what extent
      biodegradation was governed by bioavailability limitations. It was demonstrated
      that HPCD extraction followed solid-phase extraction and removed primarily
      readily bioavailable PAHs, while Triton X-100 extracted both readily and poorly
      bioavailable PAHs. Moreover, HPCD did not affect the degradation of PAHs in
      biodegradation experiments, while Triton X-100 enhanced the degradation of low
      molecular weight PAHs. It was concluded that HPCD extraction may provide a good
      method for the prediction of PAH bioavailability. Triton X-100 extraction is
      unfit for the prediction of PAH bioavailability.

PMID- 11951992
TI  - The effects of natural and synthetic steroid estrogens in relation to their
      environmental occurrence.
AB  - Laboratory-based acute toxicity data and physiological studies relating to
      natural and synthetic steroid estrogens in a range of animals and plants are
      reviewed. Steroid estrogens may induce adverse effects in animals that do or do
      not express the estrogen receptor, and in plants, and they may mimic other
      hormones or induce nonestrogenic effects. Although the findings of such studies
      should be treated with caution when extrapolated to possible environmental
      effects, the available data indicate that a wide range of effects may be
      manifested in a diversity of species. The environmental occurrence of the
      compounds and possible environmental exposure routes are also reviewed and
      discussed in relation to the laboratory-based acute toxicity data. While there
      are likely to be difficulties in relating some of the observed laboratory data to
      possible environmental effects, studies undertaken on fish are directly relevant
      because exposure pathways and concentrations were related to those occurring in
      the environment. Effects that may occur in the environment are discussed in
      relation to their significance to the individual and at the species level.

PMID- 11951993
TI  - In silico approaches to mechanistic and predictive toxicology: an introduction to
      bioinformatics for toxicologists.
AB  - Bioinformatics, or in silico biology, is a rapidly growing field that encompasses
      the theory and application of computational approaches to model, predict, and
      explain biological function at the molecular level. This information rich field
      requires new skills and new understanding of genome-scale studies in order to
      take advantage of the rapidly increasing amount of sequence, expression, and
      structure information in public and private databases. Toxicologists are poised
      to take advantage of the large public databases in an effort to decipher the
      molecular basis of toxicity. With the advent of high-throughput sequencing and
      computational methodologies, expressed sequences can be rapidly detected and
      quantitated in target tissues by database searching. Novel genes can also be
      isolated in silico, while their function can be predicted and characterized by
      virtue of sequence homology to other known proteins. Genomic DNA sequence data
      can be exploited to predict target genes and their modes of regulation, as well
      as identify susceptible genotypes based on single nucleotide polymorphism data.
      In addition, highly parallel gene expression profiling technologies will allow
      toxicologists to mine large databases of gene expression data to discover
      molecular biomarkers and other diagnostic and prognostic genes or expression
      profiles. This review serves to introduce to toxicologists the concepts of in
      silico biology most relevant to mechanistic and predictive toxicology, while
      highlighting the applicability of in silico methods using select examples.

PMID- 11951994
TI  - Antimicrobial susceptibility of Haemophilus influenzae from children in Beijing.

PMID- 11951996
TI  - Cardiovascular responses to submaximal treadmill running in 11 to 13 year olds.
AB  - The influence of age, sex, maturity, body size and body fatness on cardiac output
      (Q) and stroke volume (SV) during treadmill running at 2.22 m x s(-1) was
      examined longitudinally. Mass, stature, triceps and subscapular skinfold
      thickness, and oxygen uptake (VO2) were recorded and Q was estimated using the
      CO2 rebreathing technique on each of three annual measurement occasions. Maturity
      was assessed using the indices for pubic hair described by Tanner. At the onset,
      subjects were 11.3 (0.4) y of age and data were available from a total of 274 Q
      determinations with equal numbers from boys and girls. Age-, sex- and maturity
      associated changes in Q and SV adjusted for differences in body size and fatness
      were examined using multilevel regression modelling within an allometric
      framework. Changes in Q in both sexes were essentially in direct proportion to
      body surface area but, even with anthropometric variables controlled for, girls
      demonstrated a lower SV than boys, which was compensated for by a higher heart
      rate (HR) at each observation. CONCLUSION: At a given level of submaximal
      exercise over the age range 11-13 y Q is directly related to body size in both
      sexes. With body size and fatness controlled for, boys have greater SVs than
      girls when exercising at the same absolute VO2, Q and treadmill running speed.
      Age and maturation do not exert independent effects on either Q or SV.

PMID- 11951995
TI  - Randomized double-blind controlled trial on the effects on iron status in the
      first year between a no added iron and standard infant formula received for three
      months.
AB  - Recent research has not only questioned the necessity of iron supplementation in
      human milk substitutes prior to weaning, but also suggested some potential
      adverse effects. This study investigated the hypothesis that infant formula need
      not contain added iron in the first 3 mo. Healthy term infants were recruited
      into a double-blind controlled trial and randomized to receive either a new no
      added iron formula (New; <0.1 mg Fe 100 ml(-1)) or a standard formula (Standard;
      0.5 mg Fe 100 ml(-1)) for the first 3 mo of life. A breastfed reference group was
      also studied. Iron status was assessed at 3 and 12 mo from heel-prick capillary
      blood samples evaluated by full blood-count analysis, including reticulocytes and
      serum ferritin. In total, 149 infants were entered (51 New, 49 Standard, 49
      breastfed) with no differences between the groups in gender distribution,
      birthweight, gestation or numbers completing the study. There were no significant
      differences between the principal outcome measures: mean values for haemoglobin,
      mean cell volume and ferritin, between the two formula-fed groups, and the
      proportion with a haemoglobin level <11 g dl(-1) or ferritin <10 microg l(-1) did
      not differ. CONCLUSION: The use of a "no added iron" infant formula in place of
      an iron-fortified formula during the first 3 mo of life did not clinically affect
      iron status at 3 and 12 mo of age. The universal supplementation of formulae with
      iron during this initial period needs further consideration.

PMID- 11951997
TI  - Inadequate leptin level negatively affects body fat loss during a weight
      reduction programme for childhood obesity.
AB  - Obesity is a typical example of a complex multifactorial disease arising from
      behavioural, environmental and genetic factors that may affect individual
      responses to dietary intake and physical activity. Observational, longitudinal
      dietary interventional studies in obese patients present contrasting reports on
      the predictive value of baseline leptin levels. We report on the effect of a
      weight reduction programme in three different groups of obese children (82
      patients in all) assembled on the basis of their baseline leptin levels adjusted
      for body mass index (BMI), gender and pubertal development. The effectiveness of
      this programme was decreased in patients with relative hyperleptinaemia or
      hypoleptinaemia compared to children with baseline leptin levels appropriate to
      BMI gender and pubertal development. CONCLUSION: Information gained from leptin
      assays could provide predictive insight into an individual's ability to lose body
      fat and may therefore have important implications for our approach to the
      treatment and prevention of childhood obesity.

PMID- 11951999
TI  - Use of the lactose H2 breath test to monitor mucosal healing in coeliac disease.
AB  - Confirmation of the diagnosis of coeliac disease requires unequivocal evidence of
      recovery on a gluten-free diet. The lactose H2 breath test is a non-invasive
      technique for detecting lactose malabsorption, and this may occur in untreated
      coeliac disease. The utility of this test was investigated in objectively
      confirming a response to gluten exclusion. The study included 44 children from
      0.9 to 14.75 y of age (median 3.2) with coeliac disease. Five children were
      asymptomatic, being identified through coeliac antibody screening. Breath tests
      were performed prior to dietary treatment. If positive, they were repeated at 4
      wk intervals following gluten exclusion. Overall, 21/44 (48%) children had
      positive breath tests at presentation. In 18/21 children on a gluten-free diet,
      this became negative after 4 wk (86%) and in all the children by 8 wk. In two
      children with positive tests at 4 wk, problems with dietary adherence were
      identified. A positive test before treatment was not associated with significant
      differences in individual symptoms, height, weight and body mass index standard
      deviation scores, serum haemoglobin or albumin. However, no positive results were
      found in the asymptomatic patients (p = 0.05). Lactose malabsorption was
      associated with earlier age of presentation (p = 0.008). CONCLUSION: The lactose
      H2 breath test objectively confirms a response to gluten exclusion. In selected
      cases it can help confirm a diagnosis of coeliac disease. However, the test tends
      to be less informative in asymptomatic patients, and in older children.

PMID- 11951998
TI  - Antimicrobial susceptibility of Haemophilus influenzae among children in Beijing,
      China, 1999-2000.
AB  - A study on the nasopharyngeal carriage and antimicrobial susceptibility of
      Haemophilus influenza among children was conducted in Beijing Children's Hospital
      from April to May 2000. The study included 292 children between 1 and 60 mo of
      age with acute upper respiratory tract infection. Nasopharyngeal swabs from these
      patients were cultured, and 105 Haemophilus influenzae strains were isolated, 3
      of which were type b. Antibiotic susceptibility of the strains was determined
      using disk diffusion and E-tests and the results compared with those of isolates
      from children with pneumonia in 1999. The carriage rate of Haemophilus influenzae
      was 36.0% (105/292). It was found that 4.8% and 1.0% of isolates were resistant
      to ampicillin and cefaclor, respectively, and 5.7%, 16.2% and 77.1% were
      resistant to chloramphenicol, tetracycline, and sulphamethoxazole/trimethoprim,
      respectively. Amoxicillin/clavulanic acid, cefuroxime, ceftriaxone, azithromycin,
      and clarithromycin were uniformly active to all strains. Compared with the data
      from 1999, there was a significant increase in resistance to tetracycline (from
      12.7% in 1999 to 16.2%) and sulphamethoxazole/trimethoprim (from 40.5% in 1999 to
      77.1%). CONCLUSION: H. influenzae isolates from outpatients in Beijing Children's
      Hospital had low ampicillin resistance and were sensitive to
      amoxicillin/clavulanic acid. Sulphamethoxazole/ trimethoprim resistance rates
      increased rapidly compared with those in the 1999 data. Further surveillance
      investigations are important for the choice of empiric therapy of acute
      respiratory tract infection.

PMID- 11952000
TI  - Inflammatory bowel disease in mother or father and neonatal outcome.
AB  - Even a minor decrease in birthweight predisposes to adult disease. Inflammatory
      bowel disease (IBD) in the mother is a risk factor for low birthweight and
      preterm infants. This study investigated the effect of IBD in the mother or
      father, adjusting for confounders, on the newborn infant, with the focus on
      birthweight and pregnancy duration. A total of 10399 single-birth mother-infant
      pairs was prospectively enrolled within the ABIS project (All Babies In Southeast
      Sweden). Outcome measures included birth week, preterm birth (<37 wk),
      birthweight, low birthweight (<2500 g), birth length, caesarean section and
      neonatal hospital care. Ulcerative colitis (UC) in the mother was associated with
      lower birthweight in the infant (adjusted difference: -330 g, adjusted 95%
      confidence interval: -509 to -150 g, p < 0.001), and with even lower birthweight
      when the mother was treated with Mesalazine or steroids. No decrease in
      birthweight was seen in infants whose mother suffered from Crohn's disease (CD)
      (adjusted difference: -65 g, adjusted 95% confidence interval: -354 to 224 g, p >
      0.05). Maternal UC or CD did not affect the pregnancy duration. The neonatal
      outcome of infants whose father suffered from UC and CD did not differ from the
      control group. CONCLUSION: UC in the mother affects the birthweight of the
      infant, which may predispose to future disease in the infant. Most women and men
      with UC and CD can, however, expect a healthy child with neither preterm birth
      nor low birthweight.

PMID- 11952001
TI  - Positive experiences and the relationship between stress and asthma in children.
AB  - Ninety children aged 6 to 13 y and suffering from chronic asthma were included in
      a prospective follow-up study lasting 18 mo in order to assess whether life
      events involving substantial positive effects on the child can protect against
      the increased risk associated with stressful life events. The main outcome
      measures included positive life events, positive long-term experiences, severely
      negative life events, chronic psychosocial stress and new asthma exacerbation.
      The results showed that, provided they occurred in close proximity to severely
      negative life events, positive life events, generally related to the child's own
      achievements, afforded protection against the increased risk of a new asthma
      exacerbation precipitated by severe events in children whose lives were marked by
      low to medium levels of chronic stress. No such effect was found in children
      exposed to high chronic stress nor did long-term positive experiences, such as
      when the child has a rewarding hobby, affect the asthma risk. CONCLUSION: Life
      events with a definite positive effect can counteract the increased risk of an
      asthma exacerbation precipitated by a severely negative life event, provided the
      chronic stress is only of low to medium level. Because this protective influence
      does not apply where there is high chronic stress, reducing this condition must
      be seen as a priority in children suffering from asthma, as these children are
      also more vulnerable to negative life events precipitating asthma exacerbation.

PMID- 11952002
TI  - Determinants of correct inhalation technique in children attending a hospital
      based asthma clinic.
AB  - Many children with asthma use their inhaler device incorrectly even after
      comprehensive inhalation instruction. The aim of this study was to identify
      factors associated with correct inhalation technique. Two hundred children with
      asthma demonstrated their inhalation technique. Patient characteristics and the
      components of inhalation instructions they had received were compared for
      children demonstrating a correct or incorrect inhalation technique. In addition,
      the inhalation technique of 47 newly referred patients was followed-up
      prospectively after repeated comprehensive instruction sessions. Seventy-eight
      percent of all patients demonstrated a correct inhalation technique. Patients who
      had received repeated instruction sessions and patients who had previously been
      asked to demonstrate the use of their inhaler during an instruction session were
      more likely than other children to demonstrate a correct inhalation technique (p
      < 0.001 and p = 0.03, respectively). Multiple logistic regression analysis showed
      that repetition of instructions was significantly associated with a correct
      inhalation technique (odds ratio (OR) 8.2, 95% CI 3.2-21.5; p < 0.0001)
      irrespective of type of inhaler used. Demonstration of the inhaler use by the
      patient was significantly associated with a correct inhalation technique for
      patients using a metered dose inhaler plus spacer device (OR 3.5, 95% CI 1.0
      12.6; p = 0.05). but not for patients using a dry powder inhaler (OR 1.6, 95% CI
      0.4-6.4; p = 0.54). The number of newly referred patients demonstrating a correct
      inhalation technique improved from 57.4% to 97.9% after three comprehensive
      instruction sessions. CONCLUSION: Inhalation instruction should be given
      repeatedly to achieve and maintain correct inhalation technique in asthmatic
      children.

PMID- 11952003
TI  - Alteration of biochemical profiles after high-dose intravenous immunoglobulin
      administration in Kawasaki disease.
AB  - Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory treatment
      for several immune-mediated diseases. Early effects of high-dose IVIG treatment
      on biochemical profiles including lipids and proteins were evaluated in patients
      with Kawasaki disease (KD). Twelve children with KD (9 boys) were treated with
      IVIG at 2 g/kg over a period of 12 h. Serial sera samples were collected from the
      patients four times: before IVIG treatment and 2 h, 24 h and 7 d after IVIG
      treatment. The samples were frozen at -20 degrees C before biochemical analysis.
      A significant decrease in albumin concentration was found 2 h and 24 h after IVIG
      treatment, but this recovered to the pretreatment level after 7 d. Total
      cholesterol and triglyceride increased slightly after 7 d. A significant decrease
      in HDL-cholesterol and C-reactive protein was seen 2 h and 24 h after IVIG
      treatment. CONCLUSION: High-dose IVIG affects immediate changes in protein
      profiles and HDL-cholesterol in KD. Changes in HDL-cholesterol induced by IVIG
      may be the result of changes in systemic protein metabolism.

PMID- 11952004
TI  - Factor V 1691 G-A mutation in children with intracardiac thrombosis: a
      prospective study.
AB  - The objective of this study was to determine the association between intracardiac
      thrombosis and hereditary causes of thrombophilia, including factor V 1691 G-A
      (factor V Leiden, FVL) and prothrombin 20210 G-A mutations. Over a period of 3 y,
      genetic risk factors were evaluated in 13 consecutive children (mean age 6.27 +/-
      5.44 y) with intracardiac thrombosis, diagnosed by cross-sectional
      echocardiography. Thrombi were localized in the left heart in four patients and
      the right heart in nine patients. All children had predisposing factors for
      thrombus formation: ventriculoatrial shunt for hydrocephalus (n = 3), indwelling
      catheter for chemotherapy (n = 5), cardiomyopathy (n = 2), sepsis (n = 1),
      homocystinuria (n = 1) and tetralogy of Fallot (n = 1). Six of the 13 children
      with intracardiac thrombosis were heterozygotes for FVL mutation. Three of these
      six children with FVL mutation had ventriculoatrial shunt for hydrocephalus, two
      children had cardiomyopathy and one had sepsis. None of the patients carried the
      prothrombin 20210 G-A mutation. CONCLUSION: It is recommended that FVL mutations
      should be investigated in all cases of intracardiac thrombosis irrespective of
      whether or not a predisposing factor is identified. When a predisposing factor is
      found antithrombotic prophylaxis may be considered in patients carrying the FVL
      mutation.

PMID- 11952005
TI  - Hypothalamo-pituitary hypothyroidism detected by neonatal screening for
      congenital hypothyroidism using measurement of thyroid-stimulating hormone and
      thyroxine.
AB  - The optimal strategy in neonatal screening for congenital hypothyroidism is still
      a subject of controversy. In Kanagawa Prefecture in Japan, simultaneous thyroid
      stimulating hormone (TSH) and T4/fT4 determination has been used, while the
      results of our program may provide valuable information. Cumulative findings were
      analysed to determine the type and frequency of thyroid disorders in infants
      detected by simultaneous TSH and T4/fT4 determination, and the TSH and T4/fT4
      screening strategy was validated. A total of 1284130 neonates were screened
      between October 1979 and September 1997 and infants followed because of low
      T4/fT4 without elevated TSH (T4 < 51.5 nmol/L or fT4 < 9 pmol/L and TSH < 15
      mU/L) were retrospectively analysed. The first survey was carried out within 6 mo
      of birth and the second in 1998; 258 infants were diagnosed with congenital
      hypothyroidism at the first medical evaluation, 15 of them with hypothalamo
      pituitary hypothyroidism. However, in the second survey, only 8 children were
      confirmed as having hypothalamo-pituitary hypothyroidism, therefore the incidence
      detected by the present strategy was 1/160516. Of 8 children with hypothalamo
      pituitary hypothyroidism, mental retardation was prevented in 3 owing to early
      treatment. CONCLUSIONS: Simultaneous measurement of TSH and T4/fT4 is a useful
      strategy for detecting hypothalamo-pituitary hypothyroidism, but more studies are
      needed to show the cost-benefits of using this strategy.

PMID- 11952006
TI  - Working together: neonatal nurse practitioners in practice.
AB  - The aim of this study was to examine the relatively new role of neonatal nurse
      practitioners (NNPs) in the United Kingdom, comparing practice in different types
      of neonatal units and work undertaken by junior medical staff (JMS). Diary
      checklists sent to the total population of qualified NNPs in neonatal units
      (NNUs) and JMS in six regional centres with qualified NNPs were returned from 68
      out of 109 qualified NNPs (62%), working in 50 different NNUs and from 25 out of
      48 JMS (52%). Direct observations (totalling 263.5 h) were made by an experienced
      neonatal nurse researcher on 30 different NNPs. Frequencies of activities and
      specific procedures were compared between groups. Observational measures included
      type and duration of activity and interactions with other members of staff. NNPs
      were found to be undertaking a range of activities: in the NNU, which usually
      involved blood sampling, siting of intravenous cannulae, presenting at ward
      rounds and teaching. Outside the unit, NNPs attended the delivery suite and the
      postnatal ward. Significant differences were found in the nature and organization
      of their work in different types of NNUs. A comparison between NNPs and JMS
      showed similar activities, with greater direct involvement by NNPs in the NNU and
      in teaching. The diary data were supported by observations and together these are
      evidence of current NNP practice. CONCLUSION: To a large extent there is an
      overlap in the work of JMS and NNPs in neonatal units, but although the clinical
      work and areas of activity are similar, there are differences in emphasis and in
      work organization.

PMID- 11952007
TI  - How clinicians in neonatal care see the introduction of neonatal nurse
      practitioners.
AB  - The aim of this study was to investigate the views of UK clinicians in neonatal
      care who were working with nurses trained as neonatal nurse practitioners (NNPs).
      A questionnaire survey was used with a total sample of senior clinicians in the
      66 neonatal units with one or more qualified NNPs. The main outcome measures were
      type and frequency of response, and similar data from NNPs were used to make
      comparisons. Data were returned from 57 of the 66 clinicians contacted (86%). NNP
      clinical practice as perceived by them was largely similar to that recorded by
      NNPs, though the clinicians expected more NNP involvement in some procedures
      (inserting central venous lines, umbilical arterial catheters, chest drains and
      peripheral arterial cannulae) than was actually found. Perceptions of the NNP
      role were similar, though the clinicians were significantly less likely to see
      taking a case-load, conducting a ward round, accepting outside referrals and
      taking charge of emergency transfers as integral elements. Reflections on the
      utilization of NNPs in neonatal care and the impact on junior medical staff
      education referred to NNPs filling gaps, a reduction in the intensity of work,
      improvements in training and in the quality of care. CONCLUSION: The introduction
      of NNPs is seen positively from the perspective of clinicians working alongside
      them in neonatal care. The development of similar models of care in countries
      where the introduction of NNPs is being considered is likely to be similarly
      supported.

PMID- 11952008
TI  - Metabolic effects in neonates receiving intravenous medium-chain triglycerides.
AB  - The effects of two lipid emulsions, one with 50% each of medium-chain and long
      chain triglycerides, and a long-chain triglycerides lipid emulsion as a control,
      were evaluated for lipid and carnitine metabolism and respiratory quotient when
      given to neonates after major surgery during a short period of total parenteral
      nutrition. Each group included 10 neonates, and all tolerated the total
      parenteral nutrition well. The relative contents of linoleic acid and alpha
      linolenic acid increased in all lipid esters in plasma and adipose tissue in both
      groups, indicating that the content of these fatty acids is sufficient even in
      the medium-chain triglycerides emulsion. The serum concentration of ketones was
      within normal limits. Free fatty acids in plasma did not increase in either
      group. The total plasma carnitine concentration decreased in both groups but the
      distribution of free carnitine and acylcarnitine did not change. The total muscle
      carnitine did not change significantly but the ratio of acylcarnitine to free
      carnitine tended to increase in muscle in the treatment group, probably an effect
      of the medium-chain triglyceride supplementation. CONCLUSIONS: The two groups
      displayed the same fatty acid pattern in plasma and adipose tissue and the same
      respiratory quotient during the treatment period. Regarding carnitine status,
      essentially the same changes were seen in the two groups. However, discrete
      changes were seen in muscle tissue in the treatment group.

PMID- 11952009
TI  - Risk factors for invasive fungal infection in neonates.
AB  - Invasive fungal infection is an uncommon, but increasing cause of morbidity and
      mortality in neonates. There are few controlled studies defining risk factors for
      the development of fungal infection in a contemporary neonatal population. This
      retrospective case-control study was undertaken to investigate antenatal,
      demographic and postnatal variables that may be potentially important in the
      development of fungal infection. Two gestation-matched controls were identified
      for each index case. Information about perinatal and demographic variables, as
      well as important neonatal outcomes, was obtained from case notes.
      Microbiological data collected included the presence of fungal colonization, and
      organisms responsible for invasive fungal infection. Over a 5-y period, 24
      infants with invasive fungal infection and 48 controls were identified. Candida
      albicans was the organism identified in 75% of cases of fungal septicaemia, and
      in all cases complicated by fungal meningitis. Preceding fungal colonization,
      pulmonary haemorrhage and intrauterine growth restriction were factors
      significantly and independently associated with invasive fungal infection. Fifty
      four percent of infants with invasive fungal infection died, and 82% of survivors
      developed chronic lung disease. CONCLUSION: Some new and potentially important
      risk factors for the development of invasive fungal infection in a contemporary
      population of infants admitted to a neonatal intensive care were identified.

PMID- 11952010
TI  - A new transcutaneous bilirubinometer, BiliCheck, used in the neonatal intensive
      care unit and the maternity ward.
AB  - Transcutaneous bilirubin (TcB) was measured with a new bilirubinometer,
      BiliCheck, in 261 jaundiced infants in the neonatal intensive care unit (NICU)
      [gestational age (GA) 25-43 wk] (group 1) and in 227 healthy jaundiced term and
      near-term infants (GA 35-43 wk) (group 2). Imprecision of a single determination
      of TcB measured on the forehead [TcB(h)], expressed as 1 standard deviation, was
      15-18 micromol l(-1). No statistically significant difference between
      intraoperator and interoperator imprecision was found. There was a good
      correlation between TcB(h) and total serum bilirubin (TSB) in both groups of
      infants, although TcB(h) was on average lower than TSB. In the NICU infants,
      TcB(h), other things being equal, was lower in males than in females, and
      decreased with increasing postnatal age, for the same TSB level. In the infants
      in both groups who had a GA > or = 35 wk, sick infants had a higher TcB(h) than
      healthy infants for the same TSB level. The differences were statistically
      significant, but small and of minor clinical significance. Blood haemoglobin
      concentration, GA and ethnic origin were not found to influence TcB(h), i.e.
      BiliCheck corrects sufficiently for these factors. In all 488 infants, TcB was
      measured at four different body sites. Measurements on the forehead and sternum
      [TcB(s)] correlated well with TSB, while measurements on the knee and foot
      correlated less well. In the NICU infants TcB(h) predicted TSB statistically
      significantly better than TcB(s), while in the healthy term and near-term infants
      TcB(h) and TcB(s) predicted TSB equally well. Therefore, the preferable body site
      for measurement of TcB under routine conditions is the forehead. By retrospective
      analysis of the data, a screening model is presented whereby TcB(h) can be used
      to screen infants who require phototherapy. We found that using screening limits
      for TcB(h), which are 70% of the currently used phototherapy limits for TSB, 80%
      of blood samples in healthy term and near-term infants, and 42% of NICU infants
      with GA > or = 32 wk, could be avoided. CONCLUSION: BiliCheck is suitable for
      screening both NICU and healthy newborn infants with jaundice, with regard to the
      need for phototherapy. The authors recommend using a TcB(h) limit which is 70% of
      the currently recommended TSB limits for phototherapy, to decide whether TSB
      needs to be measured.

PMID- 11952011
TI  - Early versus late treatment of posthaemorrhagic ventricular dilatation: results
      of a retrospective study from five neonatal intensive care units in The
      Netherlands.
AB  - Posthaemorrhagic ventricular dilatation (PHVD) in very preterm infants carries a
      poor prognosis. As earlier studies have failed to show a benefit of early
      intervention, it is recommended that PHVD be first treated when head
      circumference is rapidly increasing and/or when symptoms of raised intracranial
      pressure develop. Infants with PHVD, admitted to 5 of the 10 Dutch neonatal
      intensive care units were studied retrospectively, to investigate whether there
      was a difference in the time of onset of treatment of PHVD and, if so, whether
      this was associated with a difference in the requirement of a ventriculo
      peritoneal (VP) shunt and/or neurodevelopmental outcome. The surviving infants
      with a gestational age <34 wk, born between 1992 and 1996, diagnosed as having a
      grade III haemorrhage according to Papile on cranial ultrasound and who developed
      PHVD were included in the study. PHVD was defined as a ventricular index (VI)
      exceeding the 97th percentile according to Levene (1981), and severe PHVD as a VI
      crossing the p 97 + 4 mm line. Ninety-five infants met the entry criteria.
      Intervention was not deemed necessary in 22 infants, because of lack of
      progression. In 31 infants lumbar punctures (LP) were done before the p 97 + 4 mm
      line was crossed (early intervention). In 20/31 infants, stabilization occurred.
      In 9 a subcutaneous reservoir was placed, with subsequent stabilization in 6. In
      5/31 infants a VP shunt was eventually inserted. In 42 infants treatment was
      started once the p 97 + 4 mm line was crossed (late intervention). In 30 infants
      LPs were performed and in 17 of these a VP shunt was eventually inserted. In 11
      infants a subcutaneous reservoir was immediately inserted and in 8 of these
      infants a VP shunt was needed. In one infant a VP shunt was immediately inserted,
      without any other form of treatment. Infants with late intervention crossed the p
      97 + 4 mm earlier (p 0.03) and needed a shunt (26/42; 62%) more often than those
      with early intervention (5/31; 16%). Early LP was associated with a strongly
      reduced risk of VP-shunting (odds ratio = 0.22, 95% confidence interval: 0.08
      0.62). The number of infants who developed a moderate or severe handicap was also
      higher (11/42; 26%) in the late intervention group, compared with those not
      requiring any intervention (3/22; 14%) or treated early (5/31; 16%). CONCLUSION:
      In this retrospective study, infants receiving late intervention required shunt
      insertion significantly more often than those treated early. A randomized
      prospective intervention study, comparing early and late drainage, is required to
      further assess the role of earlier intervention.

PMID- 11952012
TI  - Elevated S100B protein as an early indicator of intracranial haemorrhage in
      infants subjected to extracorporeal membrane oxygenation.
AB  - The aim of this investigation was to verify whether plasma S100B could be a
      useful tool in identifying which infants subjected to extracorporeal membrane
      oxygenation (ECMO) might develop intracranial haemorrhage (ICH). A case-control
      study of eight infants who developed ICH during ECMO was conducted. Plasma
      samples collected daily after ECMO insertion were assessed for S100B and compared
      with those obtained from eight infants supported by ECMO who did not develop ICH.
      Cerebral ultrasound and Doppler velocimetry waveform patterns in the middle
      cerebral artery (MCA PI) were also recorded at the same time as blood sampling.
      S100B blood concentrations were significantly higher in the group of infants with
      ICH 72 h before any signs of haemorrhage could be detected by ultrasound (ICH:
      2.91 +/- 0.91 microg/L vs. control: 0.53 +/- 0.15 microg/L), reaching their peak
      at day 6, when cerebral ultrasound scan patterns were suggestive of intracranial
      haemorrhage (ICH: 3.50 +/- 1.03 microg/L vs. control: 0.66 +/- 0.27 microg/L) (p
      < 0.05, for both). The highest S100B levels were observed in the three ICH
      infants who expired during the ECMO procedure (3.43 microg/L, 4.0 microg/L, 4.12
      microg/L, respectively). MCA PI values in the ICH group were also significantly
      higher, but only 24 h before any ultrasound pattern of bleeding was detected
      (ICH: 2.31 +/- 0.22 vs control: 1.81 +/- 0.24) (p < 0.05). CONCLUSION: This study
      suggests that blood S100B measurement could be a promising tool for the
      identification of infants at risk of ICH when imaging assessment and clinical
      symptoms of haemorrhage might still be silent.

PMID- 11952013
TI  - Geographic variations in possible risk factors for severe cardiac malformations.
AB  - The aim of this study was to investigate various putative risk factors in a
      county in Sweden, described as having a 28% increased prevalence of
      cardiovascular malformations, and to compare them with the risk factors in two
      reference counties. Women giving birth in the studied counties differed in age
      and parity distribution, smoking, and educational level but these differences
      could not explain the increased risk of cardiovascular malformations in the
      county, since after stratification for these variables, the risk estimate did not
      change substantially. A number of potential risk factors were studied in a
      case/control design: spontaneous abortions, involuntary childlessness, maternal
      disease, body mass index, medical drug use, alcohol use, parental employment,
      paternal age, and urban/rural residency. No single factor could be attributed to
      the increased rate, with the exception of living in a rural district. Nearly all
      risk factors, however, were stronger in the county studied than those in the
      reference counties (0.02 > p > 0.01). CONCLUSION: The only single putative risk
      factor that could have contributed to the increased risk for cardiac defects
      described in the county studied was maternal residency in a rural district.
      Notably, nearly all potential risk factors studied were stronger in the county
      studied compared with those in the reference area. A conceivable explanation is
      that one or more unidentified factors related to rural residency could potentiate
      prevalent and weak teratogenic risk factors for cardiac defects.

PMID- 11952014
TI  - Language impairment in Swedish bilingual children: a comparison between bilingual
      and monolingual children in Malmo.
AB  - In this study two groups of children were compared, 192 bilingual and 246
      monolingual, referred over a 12-mo period to University Hospital in Malmo for
      suspected language impairment. Compared with monolingual children, bilingual
      children ran a significantly lower risk (RR = 0.76, p < 0.0001) of being referred
      by a child health centre, and a significantly higher risk (RR= 1.54, p < 0.0103)
      of being referred after 5 y of age. In the bilingual group there was also a
      significantly higher risk of parental refusal of assessment (RR = 2.35, p <
      0.0016) and of the children being diagnosed with a severe language impairment (RR
      = 1.87, p < 0.0009). The risk for bilingual children with severe language
      impairment being discharged owing to non-attendance was high (RR = 6.20, p <
      0.0002) compared to monolingual children. The risk increased with severity of
      language impairment. CONCLUSION: Bilingual children displayed a higher risk of a
      diagnosis of severe language impairment and of being discharged for non
      attendance. The problem of low compliance among bilingual parents, despite strong
      indications of parental distress, must be addressed.

PMID- 11952015
TI  - Effect of BCG vaccine on tuberculin skin tests in 1-6-year-old children.
AB  - Bacillus Calmette Guerin (BCG) vaccination used in the prevention of tuberculosis
      may cause problems in interpreting the tuberculin skin test (TST), which is
      commonly used in the diagnosis of infection. A limited number of studies have
      been undertaken to investigate how length of time after BCG vaccination affects
      TST results. TST induration values of unvaccinated children were compared with
      those of children vaccinated once in order to determine the changes in TST
      responses after BCG vaccination. Mantoux TSTs were administered to 1145 children
      aged 1-6 y and induration was measured at 72 h. BCG scar status and average TST
      induration diameters were identified for each age group. CONCLUSION: Average TST
      induration in vaccinated children is significantly higher than that in
      unvaccinated children, and in the vaccinated group there is no statistically
      significant difference between induration values in the different age groups. BCG
      vaccination at the age of 0-2 mo affects TST for a long period and this condition
      does not change until 6 y of age.

PMID- 11952016
TI  - Liver involvement in alpha1-antitrypsin-deficient phenotypes PiSZ and PiMZ.
AB  - The long-term outcome of 3 PiSZ and 57 PiMZ children affected by alpha1
      antitrypsin deficiency-associated liver involvement during infancy was assessed.
      At 5 and 10 y of age all PiSZ and PiMZ children exhibited normal levels of liver
      enzymes. All families, except one, were deterred from smoking following
      counselling. CONCLUSION: Transient liver involvement observed during early
      infancy is likely to be a benign self-limiting process.

PMID- 11952017
TI  - Prospects of vaccination as a means of preventing mother-to-child transmission of
      HIV-I.
AB  - Although short-course antiretroviral therapy is efficient in reducing mother-to
      child transmission (MTCT) of HIV-1, it does not prevent transmission during the
      breastfeeding period. There is therefore an urgent need to test various
      approaches, including HIV-1 vaccination, to try to prevent postnatal transmission
      of HIV-1 in breastfeeding populations in developing countries.

PMID- 11952018
TI  - Cerebral venous sinus thrombosis in a neonate due to factor V Leiden deficiency.
AB  - A case is described of cerebral venous sinus thrombosis due to factor V Leiden
      deficiency that occurred in the neonatal period, presenting with seizures.
      Diagnosis was based on ultrasonography, Doppler ultrasound (US) and magnetic
      resonance imaging (MRI). The aetiology was only recognized after blood-clotting
      tests, antithrombin III, C and S protein levels and factor V Leiden were studied.
      This situation was treated with intravenous heparin controlled by activated
      partial thromboplastin time (APTT). MRI angiography and Doppler US were important
      in the follow-up. It is important to assess periodically the neurological
      development of the baby and to prevent situations such as dehydration or severe
      infection, which can precipitate further thrombotic events. Molecular genetics
      allowed the identification of this trait in other family members. CONCLUSION: In
      every newborn with a thrombotic episode, coagulation studies must be performed,
      including testing for activated protein C (APC) resistance. Doppler US flow
      measurement and the MRI studies provide the best tools for diagnosis and follow
      up. Heparin should be given to double the initial individual APTT. It is
      important to prevent any risk situation such as dehydration or severe infection,
      which could lead to a recurrence of a thrombotic episode. Regular assessment of
      the child's neurodevelopment is an important aspect of further care.

PMID- 11952019
TI  - Visceral leishmaniasis as a cause of unexplained fever and cytopenia in systemic
      lupus erythematosus.

PMID- 11952020
TI  - Therapeutic drug monitoring of immunosuppressant drugs in clinical practice.
AB  - BACKGROUND: Therapeutic drug monitoring (TDM) is essential to maintain the
      efficacy of many immunosuppressant drugs while minimizing their toxicity. TDM has
      become more refined with the development of new monitoring techniques and more
      specific assays. OBJECTIVE: This article summarizes current data on TDM of the
      following immunosuppressant drugs used in organ transplantation: cyclosporine,
      tacrolimus, sirolimus, everolimus, and mycophenolate mofetil. METHODS: Published
      data were identified by a MEDLINE search of the English-language literature
      through March 2001 using the terms therapeutic drug monitoring, cyclosporine,
      tacrolimus, sirolimus, everolimus, and mycophenolate mofetil. Relevant conference
      abstracts were also included. RESULTS: TDM of cyclosporine has been well studied,
      and recent findings indicate that monitoring of drug levels 2 hours after dosing
      is a more sensitive predictor of outcome than trough (C0) monitoring. C0 levels
      are being used more widely in TDM of tacrolimus; however, the relationship
      between C0 and area under the curve has varied widely in clinical trials, with
      correlations ranging from 0.11 to 0.92. The use of TDM of sirolimus, everolimus,
      and mycophenolate mofetil is evolving rapidly. CONCLUSIONS: TDM of
      immunosuppressant drugs that have a narrow therapeutic index is an increasingly
      useful tool for minimizing drug toxicity while maximizing prevention of graft
      loss and organ rejection.

PMID- 11952021
TI  - Caspofungin: an echinocandin antifungal agent.
AB  - BACKGROUND: The mainstays of treatment for nosocomial fungal infections have been
      amphotericin B and azole derivatives. Caspofungin acetate is a new echinocandin
      antifungal agent with a mechanism of action that targets a structural component
      of the fungal cell wall. OBJECTIVE: This article describes the pharmacologic
      properties and potential clinical usefulness of caspofungin. METHODS: Relevant
      information was identified through searches of MEDLINE (1966-September 2001).
      Iowa Drug Information Service (1966-September 2001), and International
      Pharmaceutical Abstracts (1970-September 2001), as well as meeting abstracts of
      the Infectious Diseases Society of America and the Interscience Conference on
      Antimicrobial Agents and Chemotherapy (1996-2001), using the terms caspofungin,
      MK-0991, pneumocandin, echinocandin, candin, and beta-(1,3)-glucan inhibitor.
      RESULTS: In vitro, caspofungin exhibits antifungal activity against an array of
      clinically important yeasts and molds, including Candida and Aspergillus spp. The
      proposed susceptibility breakpoint for caspofungin against Candida spp, the most
      common cause of nosocomial fungal infections, is a minimum inhibitory
      concentration of < or =1 microg/mL. In humans, caspofungin has a volume of
      distribution of 9.67 L, is extensively bound to albumin (97%), has a plasma
      elimination half-life of 9 to 11 hours, and is metabolized to inactive
      metabolites in the liver. Dose adjustment based on age, sex, race, or renal
      function does not appear to be necessary, although patients with moderate hepatic
      insufficiency (Child-Pugh score 7-9) should receive a lower maintenance dose. The
      results of clinical trials, although somewhat preliminary, suggest that
      caspofungin is effective in the treatment of esophageal and oropharyngeal
      candidiasis and invasive aspergillosis. When combined with other antifungal
      agents, caspofungin produces a synergistic or additive effect against a variety
      of clinically important fungi. The most commonly reported adverse events with
      caspofungin have included fever, infusion-related reactions, headache, nausea,
      elevations in liver transaminase levels, and histamine-type reactions. The
      recommended dosage in adults is 70 mg IV on day 1 followed by 50 mg/d, with the
      duration of treatment depending on the severity of the patient's underlying
      condition and the clinical response. CONCLUSION: Although additional studies are
      needed, caspofungin appears to be a promising agent for the treatment of patients
      with difficult-to-treat or life-threatening fungal infections.

PMID- 11952022
TI  - Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic
      control in patients with type 2 diabetes mellitus: a retrospective review of
      randomly selected medical records.
AB  - BACKGROUND: The antihyperglycemic effects of pioglitazone hydrochloride and
      rosiglitazone maleate are well documented. The results of clinical trials and
      observational studies have suggested, however, that there are individual
      differences in the effects of these drugs on blood lipid levels. OBJECTIVE: The
      present study evaluated the effects of pioglitazone and rosiglitazone on blood
      lipid levels and glycemic control in patients with type 2 diabetes mellitus.
      METHODS: This was a retrospective review of randomly selected medical records
      from 605 primary care practices in the United States in which adults with type 2
      diabetes received pioglitazone or rosiglitazone between August 1, 1999, and
      August 31, 2000. The outcome measures were mean changes in serum concentrations
      of triglycerides (TG), total cholesterol (TC), high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and
      glycosylated hemoglobin (HbA1c) values. RESULTS: Treatment with pioglitazone was
      associated with a reduction in mean TG of 55.17 mg/dL, a reduction in TC of 8.45
      mg/dL, an increase in HDL-C of 2.65 mg/dL, and a reduction in LDL-C of 5.05
      mg/dL. Treatment with rosiglitazone was associated with a reduction in mean TG of
      13.34 mg/dL, an increase in TC of 4.81 mg/dL, a reduction in HDL-C of 0.12 mg/dL,
      and an increase in LDL-C of 3.56 mg/dL. With the exception of HDL-C, the
      differences in mean changes in lipid parameters between treatment groups were
      statistically significant (P < 0.001, pioglitazone vs rosiglitazone). Reductions
      in HbA1c were statistically equivalent between treatments (1.04% pioglitazone,
      1.18% rosiglitazone). CONCLUSIONS: Treatment with pioglitazone was associated
      with greater beneficial effects on blood lipid levels than treatment with
      rosiglitazone, whereas glycemic control was equivalent between the 2 treatments.

PMID- 11952023
TI  - Treatment patterns and associated symptom improvement during six months of care
      for overactive bladder: a prospective, observational study.
AB  - BACKGROUND: Several pharmacologic and nonpharmacologic interventions are
      available for the treatment of symptoms of overactive bladder (OAB). The
      relationship between type of initial intervention and subsequent symptom
      improvement and resource utilization has not been explored in detail. OBJECTIVE:
      The purpose of this study was to assess (1) the proportion of patients continuing
      with their initially prescribed treatment for OAB 3 and 6 months after the
      initial evaluation and (2) the relationship between actual treatment patterns,
      symptom improvement. and number of physician office visits. METHODS: A total of
      31 physicians enrolled patients with OAB for this 6-month prospective,
      observational study. Baseline data on OAB symptom severity and OAB management
      strategies were obtained and initial treatment(s) were prescribed by physicians
      during a routine office visit. Follow-up data on symptom changes, treatment
      changes, number of physician office visits, and the frequency of absorbent pad
      use were collected via telephone interviews with patients 3 and 6 months after
      the initial visit. Stepwise logistic regression was used to assess the
      relationship between patient characteristics, prescription of medication, and
      symptom improvement. RESULTS: A total of 213 patients were enrolled; 122 (57.3%)
      and 100 (46.9%) patients provided follow-up data at the 3-month and 6-month
      assessments, respectively. The mean age was 61.2 years; 85.2% of patients were
      female, and 77.7% were white. OAB symptom improvement was significantly related
      to being prescribed medication (odds ratio [OR], 4.3; 95% CI, 1.8-9.9) and the
      mean number of daily leakage incidents at baseline (OR, 3.2; 95% CI, 1.2-8.4).
      Although patients who were prescribed drugs at baseline tended to have fewer
      physician office visits and were less likely to be prescribed nondrug
      interventions than patients who were not treated initially with drugs, these
      differences were not statistically significant. CONCLUSIONS: Pharmacologic
      treatment for symptoms of OAB appears to be associated with greater symptom
      improvement than nonpharmacologic treatment. Larger studies of experimental
      design are needed to determine whether patients treated with medication use fewer
      nondrug interventions and require fewer physician office visits than patients
      treated without medication.

PMID- 11952025
TI  - Weekly luteal-phase dosing with enteric-coated fluoxetine 90 mg in premenstrual
      dysphoric disorder: a randomized, double-blind, placebo-controlled clinical
      trial.
AB  - BACKGROUND: Because the symptoms of premenstrual dysphoric disorder (PMDD) are
      limited to the luteal phase of the menstrual cycle, the potential benefit of
      luteal-phase dosing has been hypothesized. OBJECTIVE: This multicenter,
      randomized, double-blind, placebo-controlled, parallel-group trial evaluated the
      efficacy and tolerability of enteric-coated fluoxetine 90 mg given once or twice
      during the luteal phase for the treatment of PMDD. METHODS: Study drug was given
      14 and 7 days before expected menses during the luteal phase of 3 menstrual
      cycles. After a screening period and single-blind placebo lead-in period,
      eligible women were randomized to I of 3 treatment groups: enteric-coated
      fluoxetine 90 mg on both days (LPWDx2); placebo 14 days before menses and enteric
      coated fluoxetine 90 mg 7 days before menses (LPWDx1); or placebo on both days
      (PLC). The primary efficacy measure was change from baseline in mean luteal-phase
      scores on the Daily Record of Severity of Problems (DRSP). Secondary efficacy
      measures included scores on the Rating Scale for Premenstrual Tension Syndrome,
      Clinician-Rated (PMTS-C); the Clinical Global Impression (CGI)-Severity scale;
      and the Patient Global Impression (PGI)-Improvement scale. Quality of life was
      assessed using the Sheehan Disability Scale. RESULTS: Two hundred fifty-seven
      women were randomized to treatment. At the end of the study, the LPWDx2 group had
      statistically significant improvements in DRSP total, DRSP mood subtotal, DRSP
      social functioning subtotal, PMTS-C, CGI-Severity, PGI-Improvement, and Sheehan
      Disability Scale work and family life scores compared with LPWDx1 and PLC (each
      measure, P < 0.05). There was also a statistically significant improvement in the
      score on the social life section of the Sheehan Disability Scale with LPWDx2
      compared with PLC (P = 0.037). Across all treatment groups, 5 patients
      discontinued due to nonserious adverse events. Rates of discontinuation for any
      reason did not differ between the 3 treatment groups. CONCLUSION: The findings of
      this study support the efficacy and tolerability of enteric-coated fluoxetine 90
      mg given twice during the luteal phase of the menstrual cycle for the treatment
      of PMDD.

PMID- 11952024
TI  - Randomized, double-masked, placebo-controlled comparison of the efficacy of
      emedastine difumarate 0.05% ophthalmic solution and ketotifen fumarate 0.025%
      ophthalmic solution in the human conjunctival allergen challenge model.
AB  - BACKGROUND: Emedastine difumarate 0.05% ophthalmic solution and ketotifen
      fumarate 0.025% ophthalmic solution are 2 topical antiallergic agents available
      in the United States and other countries. Emedastine is indicated for the
      temporary relief of the signs and symptoms of allergic conjunctivitis. Ketotifen
      is indicated for the temporary relief of ocular itching caused by allergic
      conjunctivitis. OBJECTIVE: The purpose of this study was to compare the efficacy
      of these agents in the temporary relief of ocular itching due to allergic
      conjunctivitis. The 2 agents were compared with each other and with placebo
      (artificial tears) using the conjunctival allergen challenge (CAC) model.
      METHODS: This was a single-center, randomized, double-masked, placebo-controlled
      study. At visit 1, CAC was performed on eligible subjects to identify the dose
      required to elicit a positive allergic reaction. Subjects returned after 7 days
      for visit 2 to confirm the allergen dose. On day 14 (+/-3) of the study, enrolled
      subjects were randomized to 1 of 3 treatment groups: emedastine in I eye and
      placebo in the other, ketotifen in 1 eye and placebo in the other, or emedastine
      in 1 eye and ketotifen in the other. In 25 subjects, bilateral CAC was performed
      5 minutes after study medication instillation. In a second group of 20 subjects,
      CAC was performed 15 minutes after medication instillation. Itching was graded
      according to a standardized 5-point scale (0 = none to 4 = severe itching) at 3,
      5, and 10 minutes postchallenge. Differences in efficacy scores between
      treatments and versus placebo were compared using 2-sample t tests of equal
      variance. RESULTS: A total of 45 patients (mean age, 41.2 years) received
      treatment: 16 received emedastine in 1 eye and ketotifen in the other; 14
      received emedastine in 1 eye and placebo in the other; and 15 received ketotifen
      in 1 eye and placebo in the other. Both emedastine and ketotifen significantly
      inhibited itching (P < 0.05) compared with placebo at all time points after the 5
      and 15-minute CAC. Mean raw scores for the active treatments were not
      statistically different. The mean itching efficacy scores were also not
      statistically different between active treatments. No adverse events were
      reported in this study. CONCLUSION: The results of this study suggest that
      emedastine and ketotifen are not significantly different with respect to anti
      itching efficacy in the CAC model of acute allergic conjunctivitis.

PMID- 11952026
TI  - Safety and local tolerability of intramuscularly administered ertapenem diluted
      in lidocaine: a prospective, randomized, double-blind study versus intramuscular
      ceftriaxone.
AB  - BACKGROUND: Ertapenem is a new, structurally unique, parenteral beta-lactam
      antimicrobial agent that can be administered once daily. OBJECTIVE: This study
      compared the local tolerability of ertapenem 1 g once a day administered
      intramuscularly (IM) versus IM ceftriaxone, with both drugs reconstituted in
      lidocaine. METHODS: In this prospective, double-blind, multicenter study, adult
      patients with lower respiratory tract infection, skin infection, or urinary tract
      infection requiring initial parenteral therapy were randomly assigned in a 3:1
      ratio to treatment with IM ertapenem 1 g once daily or IM ceftriaxone 1 g once
      daily. Although study drugs were administered by unmasked personnel, the
      patients, investigators, and the sponsor medical reviewer were blinded. Patients
      who improved clinically could be switched to oral amoxicillin-clavulanate after
      at least 2 days of IM therapy. Tolerability and safety analyses were carried out
      for the treated population, and efficacy analyses were performed for the modified
      intent-to-treat population. RESULTS: A total of 117 patients were randomized. The
      87 patients in the ertapenem group and 30 in the ceftriaxone group received IM
      therapy for a mean duration of 4.1 and 3.8 days, respectively. During treatment,
      35.6% (31/87) of patients treated with ertapenem and 43.3% (13/30) of those
      treated with ceftriaxone experienced > or =1 symptom at the local injection site;
      the most common symptom was tenderness, followed by pain. Symptoms were moderate
      to severe in only 1 patient (1.1%) in the ertapenem group and 3 patients (10.0%)
      in the ceftriaxone group. Clinical drug-related adverse events were reported
      during IM therapy in 14 patients (16.1%) in the ertapenem group and 5 patients
      (16.7%) in the ceftriaxone group. Mean +/- SD creatine kinase concentrations,
      measured in all patients, were 204.8+/-234.8 U/L at the end of IM ertapenem
      therapy and 382.9+/-721.1 U/L at the end of IM ceftriaxone therapy; at follow-up,
      values had returned to normal or had decreased in all cases. CONCLUSIONS:
      Ertapenem 1 g (reconstituted in lidocaine) administered once daily IM was
      generally well tolerated. The tolerability and safety profiles of IM ertapenem
      therapy in this study were comparable to those of IM ceftriaxone therapy.

PMID- 11952027
TI  - A randomized, double-blind, placebo-controlled comparison of emedastine 0.05%
      ophthalmic solution with loratadine 10 mg and their combination in the human
      conjunctival allergen challenge model.
AB  - BACKGROUND: When selecting treatment for allergic conjunctivitis, a primary
      concern is whether to choose local or systemic therapy. OBJECTIVE: This study
      compared the efficacy of topical emedastine 0.05% ophthalmic solution with that
      of oral loratadine 10 mg and their combination in the conjunctival allergen
      challenge model of allergic conjunctivitis. METHODS: This was a single-center,
      randomized, double-masked, placebo-controlled, parallel-group study. At visit 1,
      eligible subjects underwent conjunctival allergen challenge to identify the dose
      required to elicit a positive allergic reaction. After 7 days, subjects returned
      for visit 2, at which the allergen dose was confirmed. At visit 3, which took
      place 2 weeks later, subjects were randomized to receive either emedastine plus
      placebo capsules, loratadine plus placebo eyedrops, or both emedastine and
      loratadine. One hour after receiving study drug, subjects were challenged with
      allergen in both eyes. Allergic signs and symptoms were graded using standardized
      5-point scales. The primary efficacy variables were itching and conjunctival
      hyperemia. Secondary efficacy variables were ciliary and episcleral hyperemia,
      chemosis, lid swelling, and tearing. Itching was graded subjectively at 3, 5, and
      10 minutes after challenge. All other variables were assessed at 5, 10, and 20
      minutes after challenge. RESULTS: Eighty subjects (mean age, 43.68 years) were
      randomized to receive study treatment. Forty subjects (20 men, 20 women) received
      emedastine plus placebo capsules, 20 (7 men, 13 women) received loratadine plus
      placebo eyedrops, and 20 (12 men, 8 women) received both active treatments. In
      the between-group efficacy comparison at visit 3, the difference in itching and
      hyperemia scores between emedastine and loratadine was statistically significant
      at all time points (all, P < 0.05). Efficacy scores for the combination of
      emedastine and loratadine were significantly better than those for loratadine
      alone at 2 of 3 time points for itching and all time points for hyperemia (P <
      0.05). The combination was significantly better than emedastine alone at I of 3
      time points for itching and 6 of 9 time points for hyperemia (P < 0.05).
      CONCLUSION: In this study, emedastine was more efficacious than loratadine for
      reducing the itching and redness associated with allergic conjunctivitis in the
      human conjunctival allergen challenge model.

PMID- 11952028
TI  - "Managing" care: we can't have it all.

PMID- 11952029
TI  - Adherence to oral antidiabetic therapy in a managed care organization: a
      comparison of monotherapy, combination therapy, and fixed-dose combination
      therapy.
AB  - BACKGROUND: Although medication adherence is one of the most important aspects of
      the management of diabetes mellitus, low rates of adherence have been documented.
      OBJECTIVE: This study sought to examine medication adherence among patients with
      diabetes mellitus in a managed care organization who were receiving antidiabetic
      monotherapy (metformin or glyburide), combination therapy (metformin and
      glyburide), or fixed-dose combination therapy (glyburide/metformin). METHODS:
      Medication adherence was evaluated through a retrospective database analysis of
      pharmacy claims. The adherence rate was defined as the sum of the days' supply of
      oral antidiabetic medication obtained by the patient during the follow-up period
      divided by the total number of days in the designated follow-up period (180
      days). Health plan members were included in the analysis if they had an index
      pharmacy claim for an oral antidiabetic medication between August 1 and December
      31, 2000, were continuously enrolled in the health plan, and were aged > or =18
      years. A 6-month pre-index period was used to classify patients as newly treated
      or previously treated. Patients were grouped according to their medication-use
      patterns. RESULTS: After adjustment for potential confounding factors, including
      overall medication burden at index, there were no significant differences in
      adherence rates among 6502 newly treated patients receiving monotherapy,
      combination therapy, or fixed-dose combination therapy. Among the 1815 previously
      treated patients receiving glyburide or metformin monotherapy who required the
      addition of the alternative agent, resulting in combination therapy, adherence
      rates were significantly lower (54.0%; 95% CI, 0.52-0.55) than in the 105
      patients receiving monotherapy who were switched to fixed-dose combination
      therapy (77.0%; 95% CI, 0.72-0.82). The 59 previously treated patients receiving
      combination therapy who were switched to fixed-dose combination therapy had a
      significant improvement in adherence after the switch (71.0% vs 87.0%; P <
      0.001). CONCLUSIONS: In a managed care organization, previously treated patients
      receiving monotherapy with an oral antidiabetic medication who required
      additional therapy exhibited significantly greater adherence when they were
      switched to fixed-dose combination therapy compared with combination therapy.
      Patients receiving combination therapy who were switched to fixed-dose
      combination therapy exhibited significantly greater adherence after the switch.

PMID- 11952030
TI  - A comparison of the renal and cardiovascular safety of celecoxib and rofecoxib.

PMID- 11952031
TI  - Guidelines for laboratory test result reporting of human immunodeficiency virus
      type 1 ribonucleic acid determination. Recommendations from a CDC working group.
      Centers for Disease Control.
AB  - Monitoring human immunodeficiency virus type 1 (HIV-1) ribonucleic acid levels
      (also known as HIV viral load) has become the standard of care for monitoring
      response to therapy in HIV-infected patients. In 1999, CDC published updated
      surveillance case definitions for HIV infection and acquired immunodeficiency
      syndrome (AIDS) reporting, including positive results of HIV-1 viral detection
      tests (CDC. Guidelines for national human immunodeficiency virus case
      surveillance, including monitoring for human immunodeficiency virus infection and
      acquired immunodeficiency syndrome. MMWR 1999;48[No. RR-131:1-28). Since 1996, an
      increased number of public and private laboratories have begun performing viral
      load tests. Results obtained with available test methods are variable, and
      laboratories present these results in different ways, indicating that guidelines
      to promote standard practice in reporting of test results are warranted. This
      report provides guidelines for standardized reporting of viral load test results
      by licensed laboratories to health-care providers and facilities for public
      health case reporting of HIV infection and AIDS. Recommended standards were
      developed through data review, input involving a working group of physicians and
      laboratorians experienced in viral load testing, and an assessment of laboratory
      practices. These guidelines were discussed, refined, and endorsed at the annual
      Human Retrovirus and Hepatitis C Laboratory Testing Conference, held March 6-9,
      2000, in Charlotte, North Carolina, with participation of representatives from
      public health, hospital, independent, and blood-collection-facility laboratories.
      Adoption of these guidelines by all public and private laboratories that perform
      HIV viral load testing will improve the quality and usefulness of viral load test
      results for the physician ordering the test and for reporting to public health
      departments.

PMID- 11952032
TI  - Antiepileptic drug selection in pediatric epilepsy.
AB  - This review article presents information concerning treatment options for various
      pediatric epilepsy syndromes. The decisions made in the selection of
      antiepileptic drugs are deternined by a number of variables that include, but are
      exclusive of, risk of seizure recurrence, patient age, epilepsy syndrome, known
      drug reactions, and prognosis of the epilepsy syndrome. The review discusses
      issues pertinent to antiepileptic drug selection including simple pharmacokinetic
      principles, antiepileptic drug formulations, and information concerning clinical
      studies using some of the antiepileptic drugs. Information is provided concerning
      the issues of seizure recurrence. Suggested paradigms for antiepileptic drug
      selection for partial seizures are provided. A table of antiepileptic drug costs
      is provided for assistance in prescribing and advising families. Psychosocial
      issues pertinent to the treatment of children are discussed.

PMID- 11952034
TI  - Differential cognitive effects of antiepileptic drugs.
AB  - As a group, children and adolescents with epilepsy have a higher prevalence of
      cognitive and behavioral disorders, although many fall within the normal
      distribution. For those affected, several causes have been identified, some of
      which may be interrelated. It has proven to be methodologically sound to isolate
      the role of specific antiepileptic drugs as a cause of cognitive impairment. The
      large body of literature that has accumulated on this topic is characterized by a
      relatively high proportion of inconclusive or contradictory observations. This
      may be due in part to the many methodological pitfalls in this area of research.
      The emerging picture is that cognitive effects caused by antiepileptic drugs are
      neither the rule nor the exception. Although certain drugs appear more likely to
      be involved, no single drug causes problems in every patient, and no drug can be
      assumed never to cause any cognitive impairment. The subgroup of patients that
      are at higher risk cannot be easily defined. Early detection of cognitive effects
      is based on actively eliciting reports of symptoms. This can be complemented by a
      screening battery in case of suspicion.

PMID- 11952033
TI  - Adolescent issues in epilepsy.
AB  - Approximately one third of new cases of epilepsy have their onset before age 20
      years. Many children will enter adolescence with epilepsy or have an onset of
      seizures during adolescence. Adolescence is a time of dramatic change in growth,
      hormonal, psychologic, and social situations. Seizure frequency, teenage
      pregnancy, driving, and alcohol and drug use often become major issues during the
      adolescent years. Furthermore, adolescents often have difficulty accepting the
      chronicity of epilepsy and complying with medications, which can result in
      physical injury and perceived or real obstacles to employment, thereby
      contributing to low morale. Both pediatricians and neurologists should be aware
      of adolescent issues in epilepsy.

PMID- 11952035
TI  - Efficacy and safety of lamotrigine in pediatric patients.
AB  - Accumulating data suggest that lamotrigine, which has been available for adult
      use in epilepsy for more than a decade in clinical practice, also confers
      effective, well-tolerated control of a range of childhood epilepsies. Lamotrigine
      is currently approved for the treatment of epilepsy by regulatory authorities in
      93 countries, more than 70 of which have approved its use in pediatric patients
      on the basis of data from well-controlled clinical trials. The controlled
      clinical trials data have been supplemented over the years by clinical practice
      data, primarily from uncontrolled studies, confirming or demonstrating additional
      efficacy of lamotrigine for a range of seizure types. This article reviews the
      data from well-controlled clinical trials and studies conducted in clinical
      practice to present an updated perspective on the efficacy and safety of
      lamotrigine in pediatric patients.

PMID- 11952036
TI  - Infantile spasms and Lennox-Gastaut syndrome.
AB  - Infantile spasms and Lennox-Gastaut syndrome are rare but are important to child
      neurologists because of the intractable nature of the seizures and the serious
      neurologic comorbidities. New antiepileptic drugs offer more alternatives for
      treating both infantile spasms and Lennox-Gastaut syndrome. Selected children
      with infantile spasms are candidates for epilepsy surgery. Vagus nerve
      stimulation, corpus callosotomy, and the ketogenic diet are all options for
      selected children with Lennox-Gastaut syndrome. The epidemiology, clinical
      manifestations of the seizures, electroencephalographic characteristics,
      prognosis, and treatment options are reviewed for infantile spasms and Lennox
      Gastaut syndrome. Additional therapies are needed for both infantile spasms and
      Lennox-Gastaut syndrome as many children fail to achieve adequate seizure control
      in spite of newer treatments.

PMID- 11952037
TI  - Eye muscle antibodies and subtype of thyroid-associated ophthalmopathy.
AB  - The eye changes associated with Graves' hyperthyroidism can be classified into
      two subtypes, congestive ophthalmopathy (CO), in which inflammatory changes in
      the periorbital tissues predominate, and ocular myopathy (OM), in which eye
      muscle damage is the main feature. Antibodies against the flavoprotein (Fp)
      subunit of succinate dehydrogenase (SDH), the 64-kd protein, and G2s, a thyroid
      and eye muscle shared protein of unknown function, are good markers of eye muscle
      cell damage in patients with OM. Another antigen associated with ophthalmopathy
      is the flavine adenine nucleotide (FAD) cofactor of several mitochondrial
      enzymes, including SDH. We tested for serum antibodies against purified human
      recombinant Fp, FAD, and a G2s fusion protein, in patients with thyroid
      associated ophthalmopathy (TAO) and control patients and subjects, in enzyme
      linked immunosorbent assay. Antibodies against Fp were detected in 32% of
      patients with TAO, 30% with Graves' hyperthyroidism (GH), 16% with Hashimoto's
      thyroiditis (HT), in 14% of patients with multi-nodular goiter (MNG), and in 6%
      of normal subjects. Antibodies against FAD were found in 24%, 30%, 24%, and 14%,
      respectively, of these patients and in 12% of the normals, while antibodies
      against G2s were detected in 50% of patients with TAO, 40% with GH, 40% with HT,
      in 29% of patients with MNG, and in 7% of normals. We also tested for antibodies
      against SDH, FAD, and G2s in 12 patients with GH who developed CO (6 patients) or
      OM (6 patients) after treatment with antithyroid drugs. Of the 6 patients who
      developed OM, antibodies against SDH preceded the onset of eye disease in 4 and
      coincided with it in 2, antibodies against G2s preceded eye muscle disease in 5
      and coincided with it in 1 patient while antibodies against FAD preceded the
      development of OM in 5 patients. Of the 6 patients who developed CO, antibodies
      against SDH were detected in only one patient and borderline levels were
      demonstrated in 1, while anti-FAD and anti-G2s each preceded the onset of eye
      signs in 6 patients. Positive sera from another group of patients with TAO, and a
      second group of normal subjects, were tested at increasing serum dilutions. Sera
      from the two groups showed similar dilution patterns, except for a few patients
      with TAO in whom increasing dilutions was associated with increased, then
      decreased, antibody levels. In this experiment the prevalences of the two
      antibodies were much greater in patients with TAO namely, 67% for anti-Fp and 89%
      for anti-G2s, while the prevalences in the normals were 11% and 22%,
      respectively. The reason for this apparent discrepancy is not clear but may
      reflect subject and assay differences. Because Fp is found within the
      mitochondrial membrane it is likely that the corresponding antibodies are
      produced after eye muscle necrosis, and do not play a role in its pathogenesis.
      The primary reaction in the eye muscle may be T-cell autoimmunity against G2s,
      although this has not been proven. The mechanism for the production of antibodies
      against G2s, FAD, and Fp in subjects who do not have ophthalmopathy is unclear.
      The significance of such antibodies in control subjects is presently being
      addressed in our laboratory.

PMID- 11952038
TI  - Thyrotropin receptor expression in orbital adipose/connective tissues from
      patients with thyroid-associated ophthalmopathy.
AB  - The TSH receptor (TSHR) is the autoantigen responsible for the hyperthyroidism of
      Graves' disease. However, whether this receptor plays a role in the development
      of Graves' ophthalmopathy (GO) is unclear. Expression of TSHr is augmented in
      orbital tissues from patients with GO, and in newly differentiated adipocytes
      derived from precursor cells within the orbit. Our recent studies suggest that
      interleukin-6 (IL-6), a cytokine elevated in the circulation of Graves' patients,
      stimulates TSHr expression in vitro in orbital preadipocyte fibroblasts. This
      cytokine might play a role in the pathogenesis of GO by stimulating TSHr
      expression within the fatty connective tissues of the orbit, allowing the
      receptor to act there as an autoantigen. Whether IL-6 also stimulates
      adipogenesis in the orbit is unclear at present, but such an effect could
      contribute to the increased volume of orbital adipose/connective tissue
      characteristic of this condition. Other cytokines, including IFN-gamma and TGF
      beta, inhibit TSHr expression and adipogenesis by orbital fibroblasts, effects
      that would seem to favor disease remission. The initiation and subsequent
      clinical severity of GO may therefore be influenced by competing inhibitory and
      stimulatory cytokine effects occurring simultaneously within the orbit. Some of
      these may impact the expression of TSHr, the putative orbital autoantigen in this
      condition.

PMID- 11952039
TI  - Orbital fibroblasts exhibit a novel pattern of responses to proinflammatory
      cytokines: potential basis for the pathogenesis of thyroid-associated
      ophthalmopathy.
AB  - Thyroid-associated ophthalmopathy (TAO) represents a process confined to the
      orbit where the connective tissue becomes inflamed and accumulates the
      glycosaminoglycan, hyaluronan. Ultimately, the orbital tissues become extensively
      remodeled. Evidence points to the recruitment and activation of T cells as
      critical elements initiating and driving the pathogenesis of TAO. The phenotype
      of orbital fibroblasts appears to be distinct from that of other types of
      fibroblasts. These cells exhibit particularly robust responses to a number of T
      cell-derived cytokines. Notable among these are the inductions of key
      inflammatory genes and their products. We hypothesize that exaggerated cellular
      responses represent the basis for the involvement of the orbit in Graves'
      disease.

PMID- 11952040
TI  - Animal models of thyroid-associated ophthalmopathy.
AB  - Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition most
      frequently associated with Graves' disease (GD). The thyrotropin receptor (TSHR)
      is an important target of the autoimmune response in both disorders. The last 5
      years have seen some progress in the development of animal models, induced with
      TSHR preparations and reproducing some or all of the features of GD and TAO with
      variable incidence. The most promising approaches have used: (1) treatment of
      AKR/N mice with cells transfected with the homologous major histocompatibility
      complex class II molecule to the recipients and the full-length human or murine
      TSHR. Approximately 20% of mice develop thyroid-stimulating antibodies (TSAB) and
      increased thyroxine levels but no thyroiditis; (2) transfer of TSHR primed T
      cells to naive syngeneic recipients. Approximately 65% of BALBc mice develop
      thyroiditis and orbital changes similar to TAO; (3) genetic immunization of NMRI
      outbred mice with the full-length human TSHR. Approximately 20% of mice develop
      TSAB, hyperthyroidism, and orbital changes.

PMID- 11952041
TI  - T-cell-mediated immunity in thyroid-associated ophthalmopathy.
AB  - Thyroid-associated ophthalmopathy (TAO) is considered to be an autoimmune
      inflammatory disorder of the extraocular muscles and the orbital fat/connective
      tissue. Recent studies analyzing T cells infiltrating retrobulbar tissues
      generated important insights into the immunopathogenesis of TAO. The present
      review focuses on advances in our understanding of mechanisms responsible for the
      autoimmune inflammation in TAO, especially T cell migration to the inflammatory
      site, T cell activation by autoantigens and costimulatory signals and their
      cytokine profile. The elucidation of these processes might lead to the
      development of novel therapeutic strategies directed against autoreactive T
      cells.

PMID- 11952042
TI  - Role of cytokines in the pathogenesis of thyroid-associated ophthalmopathy.
AB  - Thyroid-associated ophthalmopathy (TAO) is generally considered to be an
      autoimmune disorder associated with Graves' disease. However, the nature of
      autoantigen or mechanism of the development of ophthalmopathy remains unclear. In
      the present review we focus the accumulating evidence on roles of cytokines in
      the orbital tissues from patients with TAO and animal models. From the analysis
      of T-cell clones, T helper 1 (T(H)1)-like clones were predominant in cultures
      from patients with recent onset hyperthyroidism and T(H)2-like clones were
      predominant in culture form patients with more remote onset hyperthyroidism.
      T(H)1-like cytokine profiles are predominant in eye muscle tissue and related to
      the eye muscle enlargement, while T(H)2-like cytokine profiles are predominant in
      orbital fat tissue from patients with TAO and negatively related to orbital
      volume. Therefore, T(H)1-like cytokines, proinflammatory cytokines, may play a
      role on the development of eye muscle component of TAO in the acute stage. T(H)2
      like cytokines, anti-inflammatory cytokines, may play protective role in the
      chronic stage of TAO. The studies using animal models suggest the genetic
      background is involved in the pathogenesis of TAO. The studies on polymorphism of
      the cytokine genes support the proinflammatory role of T(H)1-like cytokines and
      protective role of T(H)2-like cytokines.

PMID- 11952043
TI  - Role of magnetic resonance imaging in the assessment of disease activity in
      thyroid-associated ophthalmopathy.
AB  - Two different phases in disease activity are observed during the clinical course
      of thyroid-associated ophthalmopathy (TAO). The assessment of disease activity is
      important for predicting the outcome of medical management because medical
      treatment can be effective in the active stage. The aim of this study was to
      investigate whether magnetic resonance imaging (MRI) could assess the disease
      activity in TAO. To investigate the relation between MRI-T2 signal intensity (SI)
      and extraocular muscle (EOM) size, 11 patients with TAO were evaluated. EOM sizes
      (enlargement, volume) were measured by MRI-T1 image. T2-SI of EOM was expressed
      as a percentage of temporal muscle. The reduction in T2-SI was significantly
      positively correlated with that of EOM enlargement after treatment. Additionally,
      T2-SI in pretreatment showed a significant correlation with reduction in EOM
      volume for therapeutic effect, which indicates T2-SI in pretreatment can be one
      of the reliable parameters for predicting the therapeutic outcome of treatment.
      To investigate whether MRI-T2 pattern could predict the reversibility of
      diplopia, 28 patients with Graves' disease with or without ophthalmopathy were
      evaluated. Patients with TAO with reversible diplopia showed an uniform T2
      pattern in enlarged EOM. However, in patients with irreversible diplopia caused
      by the mechanical limitation of EOM, MRI-T2 image showed no uniformity with a
      partial appearance of low T2-SI. The partial low T2-SI may indicate the progress
      of inactive (fibrotic) change in EOM after active (inflammatory) change. In
      conclusion, MRI is a useful tool for detection not only of EOM enlargement, but
      also disease activity in TAO. MRI-T2 SI and pattern can predict the outcome of
      medical management in TAO.

PMID- 11952044
TI  - Octreoscan in thyroid-associated ophthalmopathy.
AB  - Until recently, there was no imaging technique available that could be considered
      as a reliable measure of inflammation in thyroid-associated opthalmopathy (TAO).
      Pentetreotide (a synthetic derivative of somatostatin) labeled with 111In has
      been used to visualize somatostatin receptors in endocrine-related tumours in
      vivo. It has also been used to measure the orbital uptake in patients with TAO.
      An increased uptake in the orbit was found in patients with active disease. It
      was suggested that it is caused by the expression of somatostatin receptors on
      activated T-lymphocytes. Thus, a positive orbital octreoscan indicates clinically
      active eye disease in which immunosuppressive treatment might be of therapeutic
      benefit, in contrast to the fibrotic end stage. Indeed, successful
      immunosuppression with prednisone, orbital irradiation, or very recently with
      somatostatin analogues, has been demonstrated in patients with TAO and positive
      octreoscan. It is inferred that an orbital octreoscan is mainly indicated to
      select patients with TAO who will benefit from immunosuppression. However,
      limitations such as cost, nonnegligible radiation burden, nonspecific examination
      for TAO, and finally, lack of evaluation of eye muscle swelling restrict the
      widespread use of this technique. It remains to be seen if orbital octreoscan
      will become a widely available tool in the management of patients with TAO.

PMID- 11952045
TI  - Prediction of the progression of thyroid-associated ophthalmopathy at first
      ophthalmologic examination: use of a neural network.
AB  - In the present work we analyzed patients with thyroid-associated ophthalmopathy
      (TAO) at various clinical stages of disease progression and implemented a model
      of neural analysis for disease classification and prediction of progression. We
      studied 246 patients (group 1), seen only once because they had absent, minimal,
      or inactive TAO and 152 patients (group 2), seen two or more times because of
      active and/or progressive TAO. The ophthalmologic assessment included: (1) lid
      fissure measurement; (2) Hertel; (3) color vision; (4) cover test and Hess
      screen; (5) visual acuity; (6) tonometry; (7) fundus examination; (8) visual
      field; (9) orbital computed tomography (CT) scan or ultrasound. A back
      propagation model of neural network was based on the relative variations of 13
      clinical eye signs (input variables) for classification and prediction of disease
      progression (output variable). Approximately 300 eyes (20%) were randomly
      selected as a test group. Correlation between expected and calculated patients'
      classification was highly significant (p < 0.00001). Concordance between clinical
      assessment and the neural network prediction was obtained in 78 of 117 eyes
      (67%). We have developed a neural model that allows classification of TAO and
      preliminary prediction of disease progression at the first clinical examination.
      The results are validating the classification into the two groups on which our
      initial assumption was based.

PMID- 11952046
TI  - Psychosocial factors in subjects with thyroid-associated ophthalmopathy.
AB  - General agreement has emerged that the perceptions of patients of how they are
      feeling and how they are able to function in daily life should be included in the
      evaluation and monitoring of the effects of disease and treatment. Thyroid
      associated orbitopathy (TAO), an inflammatory autoimmune eye disease, affects 50%
      60% of patients with Graves' hyperthyroidism. Having blurred vision and/or
      diplopia has a detectable and significant impact on functional status and well
      being, especially in role limitations caused by physical health problems.
      Therefore, to assess the impact of TAO on quality of life, we performed a
      descriptive study on consecutive ophthalmopathy patients with varying degrees of
      severity of TAO. General quality of life was assessed using a brief,
      internationally accepted, and standardized general questionnaire: the Medical
      Outcomes Study (MOS-36). In comparison to a large German reference group, low
      scores on the MOS-36 were found. Marked and significant differences from the
      control group were especially observed for the following items: vitality, social
      functioning, mental health, health perceptions, and body pain. MOS-36 did not
      correlate with the duration or severity of the ophthalmopathy. These results
      demonstrate the impact of a common visual symptom on health status and well
      being, as measured by the MOS-36. In addition, comparison of the impact of
      various symptoms and conditions provides important and potentially clinically
      relevant information. In conclusion, we have shown that TAO has a large influence
      on the quality of life of these patients. The negative impact on well-being seems
      not to be related to the usual clinical assessment. These findings underscore the
      need for quality of-life measurements in prospective and controlled clinical
      trials.

PMID- 11952047
TI  - Medical treatment for thyroid-associated ophthalmopathy.
AB  - The medical management of thyroid-associated ophthalmopathy has been, and remains
      a clinical challenge. Several drugs have been used. Systemic steroids seem to be
      beneficial in patients with active disease. The evidence for the remaining drugs
      reported to be potentially useful, is unconvincing.

PMID- 11952048
TI  - Orbital radiotherapy for Graves' ophthalmopathy.
AB  - Orbital radiotherapy is a well-established method of treatment for severe Graves'
      ophthalmopathy, because of its anti-inflammatory and locally immunosuppressive
      effects. It has been used for 60 years. Conventional external x-ray and cobalt
      therapy have been abandoned, and most groups now use supervoltage linear
      accelerators (4-6 MeV). Cumulative doses may vary, but in most studies a
      cumulative dose of 20 Gy delivered over 2 weeks was utilized. Successful outcome
      depends on the selection of patients, because recent onset, active ophthalmopathy
      is much more favorably affected than longstanding, inactive disease. Inflammatory
      signs, recent onset eye muscle dysfunction, and optic neuropathy respond well to
      orbital radiotherapy, while proptosis and longstanding eye muscle restriction
      respond poorly. Overall, favorable responses have been reported, with few
      exceptions, in approximately 60% of cases. Combination of irradiation with high
      dose systemic glucocorticoids provides better results than either treatment
      alone. Orbital radiotherapy is well tolerated and safe. Preexisting retinopathy
      (e.g., in patients with diabetes) is a contraindication to this treatment for the
      risk of further retinal damage. No case of radiation-induced tumors has so far
      been described after orbital radiotherapy for Graves' ophthalmopathy.

PMID- 11952049
TI  - Radiotherapy for Graves' ophthalmopathy: results at one year.
AB  - We report on a prospective, randomized, double-masked, internally controlled,
      clinical trial of external beam radiotherapy for patients with mild to moderate
      Graves' ophthalmopathy. Forty two patients entered the study and after giving
      informed consent had radiotherapy to one randomly selected orbit and sham
      radiotherapy to the other side. Six months later the alternate orbit was treated.
      Neither the patient nor those assessing treatment response were aware of which
      orbit had been treated. Measurements made included: lid fissure width, range of
      extraocular muscle motion, area of diplopia fields, volume of extraocular muscle
      and fat, proptosis. Patients were seen at three month intervals on a rigid follow
      up schedule. Six months after study entry no evidence of clinically or
      statistically significant benefit from radiotherapy was apparent in any measured
      parameter in the treated versus the untreated orbit. Patients treated six months
      earlier in the course of their illness fared no better than patients treated
      later. Previous steroid therapy and the value of the clinical activity score did
      not affect outcome. Since orbital radiotherapy is not free of risk and does not
      appear to be effective, it's place in therapy of Graves disease should be
      reassessed.

PMID- 11952050
TI  - Ophthalmic surgery in dysthyroid ophthalmopathy.
AB  - The major focus of this study is to evaluate the ophthalmic surgery performed to
      treat patients with various eye changes of dysthyroid ophthalmopathy (DO) in
      Japan. The medical charts of DO cases that underwent eye surgery at the Olympia
      Eye Hospital in 1999 were reviewed. In 1999, 898 patients underwent
      ophthalmologic examination at the thyroid eye clinic in our hospital, and 51
      cases were excluded out of the first visiting cases because they were
      hyperthyroid only and not associated with ophthalmopathy. This study consists of
      847 cases (151 male, 696 female), mean age of 40.9 +/- 14.7 years, age
      distribution of 10-84 years. Surgical therapy was used on 129 eyes of 93 cases
      (11%) among the 847 patients. Orbital decompression was performed on 26 eyes of
      15 cases. Most Japanese patients are not associated with a strong degree of
      proptosis, showing on average less than 20 mm. Cases with 25 mm of proptosis were
      scarcely observed. Extraocular muscle surgery was performed on 84 eyes of 60
      cases (bilateral 17 cases, unilateral 33 cases). Types of diplopia are as
      follows: upward gaze, 28 cases; outward gaze, 10 cases; downward gaze, 2 cases;
      and complex type, 10 cases. Concerning the pathogenesis of diplopia in DO,
      fibrotic change plays a dominant role, in which cicatrical adhesion to the
      surface of the muscle is always observed in extraocular muscle surgery. After
      removal of cicatrical adhesion, the forced duction is completely recovered. This
      explains the precise mechanism of this involvement. Eyelid surgery was used on 39
      eyes of 30 cases (upper eyelid, 33 eyes; lower eyelid, 6 eyes). Eyelid surgery
      was indicated for treatment of various anterior eye changes including upper
      eyelid retraction, entropion of eyelids. Better results and few complications are
      considered attributable to the stabilization of orbitopathy.

PMID- 11952051
TI  - Total thyroidectomy for the treatment of hyperthyroidism in patients with
      ophthalmopathy.
AB  - Total thyroidectomy was performed in 54 cases of Graves' ophthalmopathy from 1971
      to August 2000. There were no surgical complications except for one case of mild
      hypocalcemia. The patients' postoperative lives were not disturbed. Ocular
      symptoms and signs were much improved after total thyroidectomy in most cases,
      but the ocular protrusion was reduced 0.9 mm on average (from 20.6 to 19.7 mm),
      and this improvement was not statistically significant. However, removal of the
      thyroid tissue was not complete in some cases in this series and the residual
      thyroid tissue may continuously support the progress of ophthalmopathy. Surgical
      influences on Graves' ophthalmopathy were compared between total and subtotal
      thyroidectomy in each of 50 gender- and age-matched cases from the same period.
      Average protrusion was reduced 0.9 mm after total thyroidectomy, but was
      increased 0.5 mm after subtotal thyroidectomy. In conclusion, total thyroidectomy
      can be performed as safely as subtotal thyroidectomy and is more effective for
      Graves' ophthalmopathy than subtotal thyroidectomy. However, this procedure would
      not be expected to completely inactivate aggressive ophthalmopathy, even if all
      thyroid tissue was removed. In severe cases, orbital decompression, corrective
      eye muscle, and lid surgery are necessary.

PMID- 11952052
TI  - The role of the central nervous system in heatstroke: reversible profound
      depression of cerebral activity in a primate model.
AB  - BACKGROUND: The neurological manifestations of heatstroke victims vary. The exact
      sequence of the central nervous system (CNS) changes during lethal hyperthermia
      has only been partially explored, and the data covering the post-resuscitation
      CNS changes, which in most cases lead to secondary cardiac arrest, are
      insufficient. HYPOTHESIS: Following heating of the organism to cardiopulmonary
      arrest, successful resuscitation may be achieved by standard cardiopulmonary
      resuscitation (CPR), plus glucose and surface cooling. There is a characteristic
      sequence of neurological responses to hyperthermia preceding cardiopulmonary
      arrest, and questionable reversibility following successful resuscitation.
      METHODS: We exposed 12 pigtail monkeys under light anesthesia to total body
      hyperthermia (cerebral T = 42 degrees C) until cardiac arrest. We monitored EEG,
      mean arterial pressure (MAP), intracranial pressure (ICP), epidural temperatures,
      PaO2, PaCO2, serum sodium, osmolality, blood glucose, pupillary diameter, light
      response, corneal reflex, extremity movement, and seizures. RESULTS: During
      hyperthermia EEG frequency decreased and amplitude increased, followed by burst
      suppression pattern of the EEG. Then during severe hypoglycemia, EEG seizure
      activity and isoelectric EEG occurred when MAP and cerebral perfusion pressure
      (CPP) decreased while ICP was almost unchanged. Pupils were first responsive to
      light and became gradually unresponsive with maximal dilation, correlating with
      low CPP. After temporarily successful cardiopulmonary resuscitation (restoration
      of spontaneous circulation), normal EEG tracing and reversibility of the
      unresponsive pupils were observed. As shock led to secondary rearrest,
      deterioration with depression of all cerebral functions was documented. Some 147
      min after restoration of spontaneous circulation, brains were macroscopically
      (and microscopically) normal in six of the eight monkeys. CONCLUSIONS: The acute
      cerebral derangements during and after lethal hyperthermia are reversible. The
      cause of death is probably not CNS damage, but systemic hemodynamic
      deterioration.

PMID- 11952053
TI  - Effect of lower body negative pressure against orthostatic intolerance induced by
      21 days head-down tilt bed rest.
AB  - BACKGROUND: Exposure to actual or simulated weightlessness is known to induce
      orthostatic intolerance in humans. Many different methods have been suggested to
      counteract orthostatic hypotension. The repetitive or prolonged application of
      lower body negative pressure (LBNP) has shown beneficial effects to counter
      orthostatic intolerance, but devoting so much time to countermeasures is not
      compatible with space mission objectives or costs. The purpose of the present
      study was to assess the effects of brief LBNP sessions against orthostatic
      intolerance during a 21-d head-down tilt (HDT) bed rest. METHODS: There were 12
      healthy male volunteers who were exposed to -6 degrees HDT bed rest for 21 d. Six
      subjects received -30 mm Hg LBNP sessions for 1 h x d(-1) from day 15 to day 21
      of the HDT, and six others served as control. Orthostatic tolerance was assessed
      by means of standard tilt test. RESULTS: Before HDT, all the subjects in the two
      groups completed the tilt tests. After 21 d of HDT, five subjects of the control
      group and one subject of the LBNP group could not complete the tilt test due to
      presyncopal or syncopal symptoms. The mean upright time in the control group 13.0
      +/- 4.0 min) was significantly shorter (p < 0.05) than that in the LBNP group
      (19.0 +/- 2.2 min). Body weight decreased significantly in the control group
      during HDT, while increasing significantly on day 21 of HDT in the LBNP group.
      Urine volume increased on days 15-21 of HDT in the control group, but remained
      unchanged throughout HDT in the LBNP group. A significant decrease in cardiac
      output and cardiac index, and a significant increase in total peripheral
      resistance, pre-ejection period, plasma renin activity, aldosterone, and
      prostaglandin 12 were observed during HDT in both groups. There were no
      significant differences in these parameters between the two groups. CONCLUSIONS:
      Brief daily LBNP sessions were effective in preventing orthostatic intolerance
      induced by 21 d HDT bed rest. However, it did not improve cardiac pump and
      systolic functions and did not preserve volume regulating hormones.

PMID- 11952054
TI  - Single-dose bright light and/or caffeine effect on nocturnal performance.
AB  - BACKGROUND: The impact of the separate and combined effects of a 1-h exposure to
      bright light (approximately 3000 lx) and a 200-mg dose of caffeine on nocturnal
      performance was studied during a simulated shift-work schedule beginning 1730 in
      the evening and ending 1000 the next morning. HYPOTHESIS: Light and caffeine
      exposure were expected to improve nocturnal fatigue degradation. METHODS: There
      were 11 subjects tested under 4 treatment conditions: 1) 1 h Dim Light-Placebo;
      2) 1 h Bright Light-Placebo; 3) 1 h Dim Light-Caffeine; 4) 1 h Bright Light
      Caffeine. Exposure to the light occurred between 0130 and 0230 hours. Caffeine or
      placebo was administered at 0140 hours. RESULTS: Choice Reaction Time (RT)
      recorded during the four post-treatment sessions were shorter for the Bright
      Light-Caffeine, Bright Light-Placebo, and Dim Light-Caffeine conditions than for
      the Dim Light-Placebo condition. During the sessions beginning 0430 and 0830
      hours, the shortest RT was recorded for the Bright Light-Caffeine treatment. The
      largest number of trials without false alarms per session for the working memory
      task (letter cancellation) was found for the Bright Light-Caffeine condition.
      Exposure for 1 h to 3000 lx reduced melatonin concentration between 42-47% from
      0230 to 0410 hours. A 200-mg dose of caffeine also reduced melatonin levels,
      although to a lesser degree than 1 h exposure to 3000 lx. CONCLUSION: Although 1
      h exposure to bright light at 0130 hours combined with a 200-mg dose of caffeine
      maintains performance throughout the remainder of the night/early morning, a 1-h
      exposure to bright light without the caffeine may actually degrade performance.

PMID- 11952055
TI  - Optokinetic stimuli: motion sickness, visual acuity, and eye movements.
AB  - BACKGROUND: It is commonly assumed that motion sickness caused by moving visual
      scenes arises from the illusion of self-motion (i.e., vection). HYPOTHESES: Both
      studies reported here investigated whether sickness and vection were correlated.
      The first study compared sickness and vection created by real and virtual visual
      displays. The second study investigated whether visual fixation to suppress eye
      movements affected motion sickness or vection. METHOD: In the first experiment
      subjects viewed an optokinetic drum and a virtual simulation of the optokinetic
      drum. The second experiment investigated two conditions on a virtual display: a)
      moving black and white stripes; and b) moving black and white stripes with a
      stationary cross on which subjects fixated to reduce eye movements. RESULTS: In
      the first study, ratings of motion sickness were correlated between the
      conditions (real and the virtual drum), as were ratings of vection. With both
      conditions, subjects with poor visual acuity experienced greater sickness. There
      was no correlation between ratings of vection and ratings of sickness in either
      condition. In the second study, fixation reduced motion sickness but had no
      affect on vection. Motion sickness was correlated with visual acuity without
      fixation, but not with fixation. Again, there was no correlation between vection
      and motion sickness. CONCLUSIONS: Vection is not the primary cause of sickness
      with optokinetic stimuli. Vection appears to be influenced by peripheral vision
      whereas motion sickness is influenced by central vision. When the eyes are free
      to track moving stimuli, there is an association between visual acuity and motion
      sickness. Virtual displays can create vection and may be used to investigate
      visually induced motion sickness.

PMID- 11952056
TI  - Acute mountain sickness in Jade Mountain climbers of Taiwan.
AB  - BACKGROUND: Although there are more than 200 peaks higher than 3000 m in the
      Taiwan Alps, no data on the incidence of acute mountain sickness (AMS) are
      available. This study investigated the incidence of AMS in Jade Mountain
      climbers. METHODS: The study was performed at the entrance of Jade Mountain, the
      highest peak (3952 m) in Taiwan. A standardized form was used to collect
      information. All the recorders had previously been trained in the management of
      high altitude illness. The Lake Louise consensus was used for the diagnosis of
      AMS. RESULTS: There were 93 trekkers (18 females and 71 males) who were surveyed.
      Four records with incomplete data were excluded, leaving 89 records for analysis.
      The ages ranged from 20-68 yr, with an average age of 41.1 +/- 11.2 SD. All
      subjects had a home residence below 1 km. The most common high altitude symptoms
      were headaches. Some 25 trekkers (28%) [corrected] met the diagnoses of AMS. The
      most common site of the AMS cases feeling their worst symptoms was in the midway
      overnight hut, and not on the summit. The lower the O2 saturation recorded at the
      entrance (2659 m) of Jade Mountain, the higher the score of the Lake Louise Acute
      Mountain Sickness Score (LLAMSS). CONCLUSIONS: Acute mountain sickness is a
      common problem in Taiwan summit climbers. In our study, 28% [corrected] of the
      Jade Mountain trekkers met the diagnosis of AMS; however, the incidence of AMS
      was lower than that of other studies at similar altitudes.

PMID- 11952057
TI  - Cross-country VFR crashes: pilot and contextual factors.
AB  - BACKGROUND: General Aviation (GA) cross-country crashes, particularly those
      involving weather, continue to be a major source of fatalities, with a fatality
      rate more than four times greater than for GA crashes in general. There has been
      much speculation and little solid evidence on the causes of these crashes.
      METHODS: We have designed a program of laboratory and database research into the
      causes of cross-country weather-related crashes including an analysis of air
      crashes in New Zealand between 1988 and 2000. There were 1308 reported
      occurrences in this period. We examined in detail 77 crashes where it could be
      determined that the aircraft was on a cross-country flight. RESULTS: In our first
      analysis we compared the characteristics of crashes that occurred in response to
      externally driven failures with crashes where the aircraft continued to be flown
      at the pilot's discretion up until the point of the crash. Clear differences were
      found for visibility, altitude, crash severity, and for several pilot
      characteristics. These differences are highly consistent with those found for
      previous research on pilot characteristics and crash involvement. In the second
      analysis we made comparisons between the weather-related and nonweather-related
      crashes in the discretionary control group and between subcategories of weather
      related crashes. CONCLUSIONS: These data show that weather-related crashes occur
      further into the flight and closer to the planned destination than other kinds of
      cross-country crashes in GA. Pilots involved in these crashes are younger and
      have more recent flight time than pilots involved in other crashes. Their
      increased involvement cannot be explained simply by exposure (flight-time) but
      must be due to other factors.

PMID- 11952058
TI  - Eye-tracking measures and human performance in a vigilance task.
AB  - BACKGROUND: Visual scanning is necessary for aviation safety and similar
      vigilance tasks, but little is known about its characteristics in such tasks,
      including possible changes with alertness and fatigue. We explored concurrent eye
      movements and human performance during a vigilance task designed to require
      frequent visual scanning. Effects of time and auditory stimuli were examined.
      METHOD: A corneal-reflectance, PC-based system (Eyegaze Development System, LC
      Technologies) provided eye movement measures. Stimuli were four digits in a
      rectangular array, changed at an event rate of 4 s for a task duration of 30 min.
      There were 20 subjects who were asked to respond to specific, infrequent signal
      arrays by bar press, under both 50 dBA white noise and 90 dBA intermittent and
      unpredictable sound-burst conditions, counterbalanced for order. RESULTS: With
      time-on-task, subjective fatigue ratings increased, dwell time defined as the
      total duration of fixations on target digits decreased, number of fixations
      decreased, and fixations were further from target digits in both conditions.
      Fixation durations [mean (M) = 258 ms; standard deviation (SD) = 54 ms] did not
      change significantly with time or condition. Off-target visual scan-paths were
      less frequently followed by hits than were on-target scan-paths in both
      conditions. With the sound-burst condition, fixations were closer to target
      digits and hit rates increased. CONCLUSIONS: Dwell time, number, and accuracy of
      fixations on target objects decreased with time on task, and inaccurate scan
      paths were often associated with performance errors. Sound bursts increased
      fixation accuracy and hit rate. The results provide a basis for visual scan
      analyses during vigilance tasks, with applications to alertness monitoring and
      prediction.

PMID- 11952059
TI  - Treatment of pulmonary air embolism with hyperbaric oxygen and isoproterenol in
      rats.
AB  - BACKGROUND: Pulmonary air embolism (PAE) occurs in inappropriate decompressions
      or clinical complications. Sudden lodging of air bubbles in the pulmonary
      circulation results in pulmonary hypertension, pulmonary edema, and deficiency in
      cardiopulmonary functions, which are often fatal without timely intervention. In
      this study, we investigated the effectiveness of hyperbaric oxygen (HBO2) therapy
      on the acute lung injury induced by venous air infusion in rats. METHODS:
      Systemic and pulmonary arterial pressures were monitered through catheters in the
      femoral artery and pulmonary artery, respectively. PAE was induced by venous
      infusion of air at the rate of 25 microL x min(-1). Wet/dry weight ratio of the
      lung and protein concentration and LDH activity in the bronchoalveolar lavage
      (BAL) fluid were measured at the end of the experiment. RESULTS: Air infusion
      raised the mean pulmonary arterial pressure (MPAP) within 10 min to a plateau
      that was 208% above the baseline value. The wet/dry ratio of lungs were 4.83 +/-
      0.28, 4.98 +/- 0.39, and 5.20 +/- 0.38 in the groups receiving 0.13, 0.50, and
      1.0 ml of air infusion, respectively, which were significantly higher than the
      control group that averaged 4.47 +/- 0.24. The protein concentration (mg x L(-1))
      and the LDH activity (mAbs x min(-1)) in BAL fluid increased from 291 +/- 78 and
      21.6 +/- 4.8 in the control group to 1491 +/- 402 and 83.3 +/- 15.4, 1432 +/- 278
      and 75.2 +/- 35.4, and 1809 +/- 493 and 59.6 +/- 23.3 in the lungs receiving air
      infusion for 5, 20, and 40 min, respectively. Treatment with hyperbaric oxygen at
      3 ATA or 6 ATA, or with isoproterenol reduced neither the increased wet/dry
      weight ratio nor the protein concentration and LDH activity in the BAL fluid.
      CONCLUSION: Our results demonstrated that venous air infusion induced acute lung
      injury in rats and suggested that neither HBO2 therapy nor isoproterenol
      treatment could not effectively reverse the PAE-induced lung injury.

PMID- 11952060
TI  - Goals of biomedical support of a mission to Mars and possible approaches to
      achieving them.
AB  - The main medical and biological problems associated with a piloted mission to
      Mars are discussed. Prerequisites for the mission are described, based on our
      experience with biomedical support of prolonged piloted missions. The most
      important factors are developing countermeasures against the prolonged effects of
      microgravity and hypogravity; solving a complex of psychological problems;
      developing methods to protect against cosmic radiation; and creating effective
      and reliable life support systems. Some aspects of the likely risks involved in
      such a mission are also reviewed.

PMID- 11952062
TI  - Conscientiousness and work performance while suffering from acute mountain
      sickness: a case report.
AB  - A 52-yr-old male scientist who participated in a geophysical survey in Antarctica
      from a field camp located at 3538 m (11,600 ft) experienced specific symptoms of
      acute mountain sickness (AMS) by Mission Day 9, and full syndrome AMS by Mission
      Day 12. He was treated at the field camp and evacuated to sea level on the next
      available flight (Mission Day 15). The concerns of this highly conscientious
      individual that initial signs of illness, such as fatigue with exertion, could be
      misinterpreted by others as poor work performance are described. The report
      focuses on individual personality and group processes that could lead to
      nondisclosure of symptoms, and the need, particularly in long-duration missions
      in which evacuation is difficult or impossible, to sensitize personnel to the
      importance of recognizing and reporting potential health problems.

PMID- 11952061
TI  - Central retinal artery occlusion by proxy: a cause for sudden blindness in an
      airline passenger.
AB  - The use of gas media in ophthalmologic procedures is relatively commonplace.
      Scleral buckle and pneumatic retinopexy procedures using air-gas mediums are a
      widely accepted treatment for retinal detachment. We present a patient who had a
      scleral buckle with pneumatic retinopexy performed and subsequently flew in a
      commercial airliner 2 wk later. The patient experienced sudden blindness due to
      central retinal artery occlusion brought about by expansion of the air bubble
      when the aircraft reached cruise altitude and a cabin pressure of 8000 ft. The
      intraocular pressure exceeded the central artery pressure thereby collapsing the
      artery. The patient's symptoms were relieved when an onboard flight surgeon
      identified the problem and the cabin pressure was reset to 2000 ft. Flying after
      an ophthalmic procedure that incorporates intraocular gas may have complications
      due to the bubble expansion in accordance with Boyle's Law. The ophthalmologic
      surgeon must be diligent in forewarning patients of the potential complications
      of flying for weeks to months after a procedure that utilizes intraocular gas.

PMID- 11952063
TI  - Delayed treatment of frostbite injury with hyperbaric oxygen therapy: a case
      report.
AB  - The effects of hyperbaric oxygen therapy on skin microcirculation were evaluated
      by laser-Doppler flowmetry and vital capillary microscopy in a frostbite victim 2
      wk after the injury. Laser-Doppler skin blood flow, measured in intact skin on
      the dorsum of the foot, decreased from 52 to 31 perfusion units during hyperbaric
      oxygen therapy. The number of visible nutritive capillaries in frostbitten areas
      on the toes increased from 2 to 12 per mm2, as measured immediately after the
      hyperbaric oxygen therapy. We conclude that hyperbaric oxygen therapy is capable
      of improving nutritive skin blood flow in frostbitten areas more than 2 wk after
      the injury.

PMID- 11952064
TI  - Physiological incidents during 39 years of hypobaric chamber training in Japan.
AB  - BACKGROUND: Hypobaric chamber training for military aircrew is very important for
      flight safety. Since we began hypobaric training in our laboratory in 1960, some
      trainees have suffered physiological incidents. This study will characterize the
      physiological incidents during hypobaric chamber training at the Japan Air Self
      Defense Force (JASDF). METHODS: All available training records from 1960-1998
      were reviewed and the frequency of physiological incidents counted and analyzed.
      RESULTS: There were 29,677 trainees and 58,454 exposures. Overall frequency of
      physiological incidents was 6.3%. Physiological incidents included ear pain,
      paranasal sinus pain, abdominal pain, hypoxia, hyperventilation, joint pain, and
      toothache. Decompression sickness (DCS-I, simple joint pain only) was rare. In
      cases of DCS-I, joint pain was easily relieved with controlled descent. During
      the last three decades, overall prevalence of physiological incidents has
      gradually increased from 5.3 to approximately 6.1% before 1991, to 6.8-9.9% after
      1991. However, prevalence rate showed no change through out the period when ear
      pain was factored out. The increase in prevalence was entirely due to an
      increased frequency of ear pain: 3.6 to approximately 4.6% before 1991, and 5.4
      to approximately 7.2% after 1991. CONCLUSIONS: DCS has not been a problem in the
      JASDF hypobaric chamber training experience. The majority of physiological
      incidents during hypobaric chamber training in JASDF have been ear pain, a minor
      but frequent obstacle to hypobaric training. The exact cause of the observed
      increase in frequency of Eustachian tube dysfunction currently remains unclear.

PMID- 11952065
TI  - Field experience with the FAA's Web-based medical certification system
      "AMCS/DIWS". Federal Aviation Administration.
AB  - The October 1, 1999, introduction in the U.S. of a Web-based medical
      certification process for civil aircrew opened a new era within civil aviation.
      The Federal Aviation Administration's (FAA) Aeromedical Certification
      System/Document Imaging Workflow System (AMCS/DIWS) has imposed certain new
      requirements on the designated Aviation Medical Examiners (AMEs), including the
      use of Internet systems and procedures. A number of AMEs elected to discontinue
      their work as the classic medical certification processes were replaced. The
      authors document their personal experience with respect to the new system, and
      cite the overall advantages that modernized medical certification procedures
      bring. These advantages include far fewer "mistakes of omission" by AMEs, more
      timely receipt by the FAA of aircrew certification data, and a developing master
      aircrew database for analytic studies.

PMID- 11952066
TI  - Voluntary hyperventilation into a simple mixing chamber relieves high altitude
      hypoxia.
AB  - Involuntary hyperventilation is a critical factor in acclimatization to a high
      altitude. Unacclimatized subjects do poorly when acutely exposed to high
      altitude. This may not be due to hypocapnia itself, but rather an associated
      symptom which inhibits hypoxic respiratory stimulation. In an unacclimatized
      individual, voluntary hyperventilation may greatly relieve hypoxia and may be an
      alternative to involuntary hyperventilation. However, subjects voluntarily
      hyperventilating may overventilate and become disabled from severe hypocapnia. A
      simple mixing chamber is described which makes voluntary hyperventilation easier,
      safer, and possibly more effective. A subject breathing into a mixing chamber was
      able to maintain an SaO2 of 90% at 20,000 ft.

PMID- 11952067
TI  - Cases from the aerospace medicine residents' teaching file: atrial fibrillation.
AB  - An Army aviator in training develops recurrent episodes of tachycardia diagnosed
      as atrial fibrillation. The presentation, diagnosis, treatment, and aeromedical
      issues surrounding atrial fibrillation are discussed.

PMID- 11952068
TI  - Ocular correlates of fatigue.

PMID- 11952069
TI  - Continuous midazolam versus diazepam infusion for refractory convulsive status
      epilepticus.
AB  - The objective of this study was to compare the efficacy of continuous midazolam
      and diazepam infusion for the control of refractory status epilepticus. An open
      label, randomized control study was undertaken at the Pediatric Emergency and
      Intensive Care Service of a multidisciplinary teaching and referral hospital.
      Subjects included 40 children, 2 to 12 years of age, with refractory status
      epilepticus (motor seizures uncontrolled after two doses of diazepam, 0.3 mg/kg
      per dose, and phenytoin infusion, 20 mg/kg). Either continuous midazolam (n = 21)
      or diazepam infusion (n = 19) in incremental doses was administered. The primary
      outcome measure was the proportion of children in each group with successful
      control of refractory status epilepticus. The secondary outcome measure was the
      time to control seizure activity, recurrence of seizure after initial control, if
      any, the frequency of hypotension, and the need for ventilation. The two groups
      were similar in age (mean +/- SD = 4.9 +/- 43.6 months) and etiology. Twenty
      three (57.5%) patients had acute central nervous system infection. Refractory
      status epilepticus was controlled in 18 (86%) and 17 (89%) patients in the
      midazolam and diazepam groups, respectively (P = not significant). The median
      time to seizure control was 16 minutes in both groups, but in the midazolam
      group, seizures recurred in more children (57% versus 16% in diazepam group; P <
      .05). The maximum dose (mean +/- SD) of midazolam and diazepam required was 5.3
      +/- 2.6 microg/kg/min and 0.04 +/- 0.02 mg/kg/min, respectively. About half of
      the patients needed mechanical ventilation and 40% had hypotension in both
      groups, but the mortality was higher in the midazolam group (38%) as compared to
      the diazepam group (10.5%, P < .1 > .05). Continuous midazolam and diazepam
      infusions were equally effective for control of refractory status epilepticus.
      However, midazolam was associated with more seizure recurrence and higher
      mortality in refractory status epilepticus predominantly caused by central
      nervous system infections.

PMID- 11952070
TI  - Kindergarten readiness skills in children with sickle cell disease: evidence of
      early neurocognitive damage?
AB  - Young children with sickle cell disease are at risk of brain damage, including
      stroke. We tested the hypothesis that such patients are also at risk of cognitive
      impairment. We characterized the cognitive ability of kindergarten children to
      minimize the effect of disease-related school absence. The Memphis City Schools
      use the Developing Skills Checklist, a teacher-administered test given in the
      classroom, to assess kindergarten-appropriate skills. Data were obtained for 34
      patients, who were matched to controls by gender, race, date of birth, school,
      and approximate income. Two controls were selected for each patient, and paired t
      tests were used to compare patient's scores to composite control scores. Patients
      scored lower than controls in auditory discrimination (P < .01), and there was a
      trend (P < .10) toward lower patient scores in language. Deficits cannot be
      attributed to school absence and may predict academic problems for patients with
      sickle cell disease.

PMID- 11952071
TI  - Significance of microcephaly among children with developmental disabilities.
AB  - To assess the clinical impact of microcephaly among children with developmental
      disabilities, we reviewed the charts of 1393 consecutive patients from birth to 5
      years of age referred to our child development center. Comparisons were made
      between normal and low IQ microcephalic patients and between children with
      cerebral palsy with and without small head circumference. Microcephaly was
      detected in 15.4% of patients. Although mental retardation was more common among
      microcephalic children (P < .001), almost half had normal intelligence.
      Prematurity (P < .001), perinatal asphyxia (P < .001), small for gestational age
      (P < .001), respiratory distress syndrome (P < .001), and brain hemorrhage (P <
      .001) were associated with microcephaly. Hypotonia (P < .001) and spasticity (P <
      .001) were the most common neurologic findings. Cerebral palsy (P < .001), growth
      retardation (P < .001), epilepsy (P < .001), and strabismus (P < .001) were the
      main associated diagnoses found. Mental retardation was significantly more common
      among microcephalic patients with cerebral palsy than among normocephalic ones (P
      < .0004). Microcephaly is common among children evaluated for developmental
      disabilities. Many of these patients have normal or borderline IQ. Of several
      perinatal conditions associated with later microcephaly, respiratory distress
      syndrome and intraventricular hemorrhage show the strongest correlation. Mental
      retardation is not a risk factor for other neurologic complications in
      microcephalic children. However, in children with cerebral palsy, microcephaly is
      a risk factor for mental retardation.

PMID- 11952072
TI  - Effects of intranasal midazolam and rectal diazepam on acute convulsions in
      children: prospective randomized study.
AB  - In this study, the effects and side effects of rectal diazepam and intranasal
      midazolam were compared in the treatment of acute convulsions in children to
      develop a practical and safe treatment protocol. In the diazepam group, the
      seizures of 13 (60%) patients terminated in 10 minutes; however, 9 (40%) patients
      did not respond. In the midazolam group, 20 (87%) patients responded in 10
      minutes, but 3 (13%) patients did not respond. Regarding the anticonvulsant
      effect, midazolam was found to be more effective than diazepam, and the
      difference was statistically significant (P < .05). The necessity of a second
      drug for the seizures that did not stop with the first drug was higher in the
      diazepam group than the midazolam group, and the difference was statistically
      significant (P < .05). We conclude that as an antiepileptic agent, intranasal
      midazolam is more effective than rectal diazepam. After administration, we did
      not observe any serious complications. Further investigations are necessary;
      however, intranasal administration is easy, so if the nasal drop and spray forms
      used in some European countries and the United States are available worldwide, it
      will be very useful for physicians in the emergency room.

PMID- 11952074
TI  - Pontocerebellar hypoplasia type 2 and Reye-like syndrome.
AB  - Pontocerebellar hypoplasia is an autosomal recessive syndrome with onset during
      the fetal period. Two subtypes of pontocerebellar hypoplasia have been described
      on the basis of clinical and neuropathologic criteria. Pontocerebellar hypoplasia
      type 2 is characterized by progressive microcephaly, early onset of
      extrapyramidal dyskinesia, and near absence of motor and cognitive development,
      without signs of either spinal or peripheral involvement. We report a clinical
      observation of a patient with pontocerebellar hypoplasia type 2, a 3-year-old
      girl with progressive microcephaly, dystonic limb movements, and absence of motor
      and cognitive development. Cranial magnetic resonance imaging revealed
      pontocerebellar hypoplasia. At the age of 2 years, she suffered a Reye-like
      syndrome that worsened her condition. Differential diagnosis was established with
      intrauterine injuries, other malformative syndromes, and neurodegenerative or
      neurometabolic disorders, which can be associated with cerebellar hypoplasia.

PMID- 11952073
TI  - Electroencephalographic dipoles of spikes with and without myoclonic jerks caused
      by epilepsia partialis continua.
AB  - We used electroencephalographic (EEG) dipole analysis to investigate the
      generators of spikes with and without myoclonic jerks in a 12-year-old patient
      with epilepsia partialis continua secondary to left parietal cortical dysplasia.
      We recorded EEG and right wrist extensor electromyography (EMG) and collected 42
      spikes with jerks (jerking spikes) and 42 spikes without jerks (nonjerking
      spikes). We applied a single moving dipole model to the individual and averaged
      spikes. Dipoles at the negative peak of individual jerking and nonjerking spikes
      were localized in the dysplastic area. At the onset of the averaged jerking spike
      that preceded the EMG discharges by 20 ms, the dipole was in the motor cortex,
      whereas for the averaged nonjerking spike, the dipole was in the sensory cortex.
      The dipole moment at averaged jerking spike onset was twice that of the averaged
      nonjerking spike. Electroencephalographic dipole analysis of averaged spikes
      differentiated the generator of jerking and nonjerking spikes in epilepsia
      partialis continua. Individual dipoles demonstrated the area of epileptogenic
      cortical dysplasia.

PMID- 11952075
TI  - Open-label study of botulinum toxin for upper limb spasticity in cerebral palsy.
AB  - The objective of this study was to assess the efficacy of botulinum toxin for
      upper limb spasticity in cerebral palsy. An open-label study was conducted in 11
      children with cerebral palsy. Post-botulinum toxin assessment was conducted in
      weeks 1, 4, and 16, with averaged scores being analyzed. The Clinical Global
      Impression Scale of the mothers showed marked, moderate, and mild improvement in
      five, four, and two cases, respectively. The Modified Ashworth Spasticity Scale
      score showed a statistically significant decrease in the mean spasticity score (P
      < .003). Other tests were performed depending on the cognition of the child.
      Increase in joint motion occurred in all five children assessed using web space
      (P = .043). For the Jebson Hand Function Test, improvement occurred in all five
      cases assessed (P < .03). Four of five (80%) children could perform tasks that
      they failed before they were given botulinum toxin. Botulinum toxin is useful in
      decreasing spasticity and improving the upper limb function of young children
      with cerebral palsy with normal cognition. Motivated families should be selected
      with a specific target of using botulinum toxin as an adjunct in a habilitation
      program.

PMID- 11952076
TI  - Asperger's syndrome and cortical neuropathology.
AB  - Asperger's disorder or syndrome is characterized by impaired social interaction,
      normal intelligence, and adequate language skills in the areas of grammar and
      vocabulary. The symptoms are pervasive in nature and usually manifested in
      childhood. Despite the gravity and chronicity of the condition, the medical
      literature remains sparse and offers no information about possible
      neuropathologic underpinnings. The present study is a case report on two patients
      with Asperger's syndrome. Neuropathologic examination revealed no degenerative
      changes or gliosis. A more detailed assessment with computerized image analysis
      indicated abnormalities in the minicolumnar organization of the three areas
      examined (9, 21, 22) (P = .032). Specifically, minicolumns were smaller, and
      their component cells were more dispersed than normal. A similar neuropathology
      has recently been reported for autism and disputes the uniqueness of these
      findings. The minicolumnar changes provide a possible link to receptive field
      abnormalities and a useful clinicopathologic correlate to Asperger's syndrome.

PMID- 11952077
TI  - Complete biotinidase deficiency presenting as reversible progressive ataxia and
      sensorineural deafness.
AB  - Most symptomatic patients with biotinidase deficiency have both neurologic and
      cutaneous symptoms and typical organic aciduria. We encountered a previously
      healthy girl with complete biotinidase deficiency presenting initially at age 17
      months with episodic ataxia that became severe progressive ataxia in 2 months,
      but without skin rash or typical organic aciduria, which resolved completely with
      biotin treatment. Additionally, moderate sensorineural deafness also improved to
      the normal range. Even without typical cutaneous findings or organic aciduria,
      biotinidase deficiency should be considered among the differential diagnosis in
      any child presenting with either episodic or progressive ataxia or sensorineural
      deafness as prompt diagnosis and treatment with biotin may induce an excellent
      recovery.

PMID- 11952078
TI  - Hyperekplexia in a girl with posterior fossa malformations.
AB  - Hyperekplexia is a rare clinical syndrome of pathologic startle response to
      unexpected stimuli such as sound or touch. The majority of cases are familial.
      Sporadic cases of hyperekplexia have also been reported, mostly in association
      with brainstem pathology. We describe a girl with sporadic hyperekplexia
      secondary to previously unreported cerebellar pathology. Her symptomatology was
      predominantly unilateral, being ipsilateral to the cerebellar involvement. This
      type of presentation, which may be termed hemihyperekplexia, has not been
      described before. Response to clonazepam was good but showed diurnal variations.
      The case is being reported for its unusual features.

PMID- 11952079
TI  - Hurler's syndrome, West's syndrome, and vitamin D-dependent rickets.
AB  - Mucopolysaccharidosis I is a metabolic disease of autosomal recessive inheritance
      caused by deficient activity of alpha-L-iduronidase. The clinical phenotype
      presents a wide spectrum of signs in the first year of life. We report a child
      with clinical features and laboratory data consistent with mucopolysaccharidosis
      I who precociously developed hydrocephalus and flexion spasms with hypsarrythmia
      in the electroencephalographic registration characteristic of West's syndrome.
      His radiologic and biochemical data suggested vitamin D-dependent rickets. To our
      knowledge, this is the first report of a patient demonstrating an association
      among mucopolysaccharidosis 1, West's syndrome, and vitamin D-dependent rickets.

PMID- 11952080
TI  - Gelastic seizure with tectal tumor, lobar holoprosencephaly, and subependymal
      nodules: clinical report.
AB  - Gelastic seizures are characterized by inappropriate, stereotyped laughter and
      are often first recognized when other epileptic manifestations occur. They are
      frequently associated with hypothalamic hamartomas. Central nervous system
      developmental abnormalities are rarely reported with gelastic seizures. There is
      only one case report of gelastic seizure caused by holoprosencephaly. We report a
      2-year-old girl with multiple brain structural abnormalities including tectal
      tumor (possibly hamartoma), multiple subependymal nodules, and holoprosencephaly.
      She developed seizures during the newborn period and presented with gelastic
      seizure and simple partial seizure at 3 months of age.

PMID- 11952081
TI  - Successful treatment of severe infantile hyperekplexia with low-dose clobazam.
AB  - We report two cases of severe infantile hyperekplexia successfully treated with
      low-dose clobazam. The first case presented at 6 weeks of age with multiple
      episodes consisting of difficulty diapering because of stiffness and loud
      inspiratory noises followed by breath-holding in inspiration. She was diagnosed
      with hyperekplexia and started on clonazepam 0.05 mg daily. This was discontinued
      because of excessive sleepiness. The second case presented at 3 weeks of age with
      episodes of crying that would change in pitch and then abruptly stop, followed by
      leg and arm extension and stiffening. On occasion, there was cyanosis, and she
      received mouth-to-mouth resuscitation. She was diagnosed with hyperekplexia at 9
      months of age. Both infants were treated with clobazam (0.25 and 0.3 mg/kg/day
      respectively), resulting in resolution of symptoms with no side effects. During
      treatment, both had minimal startle response to various stimuli and have now been
      successfully weaned from clobazam. Low-dose clobazam is effective in the
      treatment of hyperekplexia and is well tolerated in infants.

PMID- 11952082
TI  - Rickettsia typhi infection presenting as subacute meningitis.
AB  - We report two children with Rickettsia typhi infection presenting with mild
      central nervous system manifestations and pleocytosis in cerebrospinal fluid.
      Murine typhus should be included in the differential diagnosis of
      meningoencephalitis in children who are residents of endemic areas.

PMID- 11952083
TI  - Zonisamide in pediatric epilepsy: review of the Japanese experience.
AB  - Zonisamide is a novel anticonvulsant that is structurally and mechanistically
      unique, compared with other antiepilepsy drugs. Available in Japan and South
      Korea since 1989, it was approved in the United States in the year 2000 as
      adjunctive therapy for partial seizures in adults. There has been extensive
      clinical trial and clinical practice experience with zonisamide therapy in
      Japanese children. Open-label data from pediatric clinical trials conducted in
      Japan suggest that zonisamide is well tolerated and effective against partial-
      and generalized-onset seizures in children. Despite this wealth of open-label
      data, no formal pharmacokinetic studies and only one well-controlled trial of
      zonisamide's efficacy and safety in Japanese children have been completed to
      date. No controlled clinical trials of zonisamide in children have been completed
      in the United States or Europe. Additional controlled trials in children with
      partial- or generalized-onset seizures, infantile spasms, and Lennox-Gastaut
      syndrome are warranted to further delineate zonisamide's broad spectrum of
      efficacy and tolerability in children.

PMID- 11952084
TI  - Statistical analyses of structural magnetic resonance imaging of the head of the
      caudate nucleus in Colombian children with attention-deficit hyperactivity
      disorder.
AB  - Magnetic resonance imaging (MRI) studies of the caudate nucleus have reported
      reversal asymmetry and alterations of its size, suggesting a striate cortical
      disorder related to attention-deficit hyperactivity disorder (ADHD). The
      objective was to evaluate whether alterations of the asymmetry and size of the
      caudate nucleus head exist in a sample of well-controlled 7- to 11-year-old
      Colombian children, with different types of ADHD. Two groups of cases-ADHD of the
      combined type and ADHD of the inattentive type-and one control group, were
      selected. Multiple methods for assessing ADHD (rating scales,
      psychologic.interview, neurologic history and examination, and neuropsychologic
      evaluation) were used to confirm the diagnoses. Participants with a history of
      language disorder, learning disabilities, depression, and other major neurologic
      and psychiatric conditions were excluded. Finally all groups had 15 children,
      matched by sex (7 male, 8 female), age, socioeconomic status, and grade. Height,
      weight, head circumference, and encephalic index were statistically controlled.
      Three T1-weighted volumetric (three-dimensional) MRI slides of the caudate
      nucleus head were obtained with a 1.5-Tesla Gyroscan apparatus. The control group
      had a significantly higher Wechsler Full-Scale IQ than the groups with ADHD of
      the combined type and ADHD of the inattentive type (P < .001). Volumes from the
      left caudate nucleus head were significantly larger than volumes from the right
      in all groups (P < .001). There were no group differences when volumes were
      compared between groups. All of the groups had left caudate nucleus head volumes
      significantly higher than right, although there were no between-group
      differences. The results in relation to previous studies are discussed.

PMID- 11952087
TI  - A novel role of RGS9: inhibition of retinal guanylyl cyclase.
AB  - Cyclic GMP plays a key role in retinal phototransduction and its photoreceptor
      concentration is precisely controlled by the cooperative action of cGMP
      phosphodiesterase (PDE) and retinal guanylyl cyclase (retGC). However, studies of
      the relationship between these two systems have focused only on a Ca2+-mediated,
      indirect connection. This article summarizes our studies strongly suggesting that
      RGS9-1 is directly involved in the cooperative action of PDE and retGC, and that
      this ingenious mechanism plays an important role in tuning of cGMP concentration
      in photoreceptors.

PMID- 11952086
TI  - Calcium-sensitive ROS-GC1 signaling outside of photoreceptors: a common theme.
AB  - Until now, ROS-GC1 signal transduction system was thought to be exclusive to
      photoreceptors in the retina. Two recent reports, however, now show that this is
      not the case. In one, the ROS-GC1 signal transduction system has been identified
      and characterized in pinealocyte neurons. This signaling is modulated by
      norepinephrine. However, the response of the individual pinealocyte neuron to the
      norepinephrine signal depends on whether the GCAP1-linked (results in
      hyperpolarization) or S100beta-linked (results in depolarization) pathway is
      operational in the pinealocyte. The GCAP1-linked pathway results in
      hyperpolarization, while the S100beta-linked pathway, in depolarization. The two
      pathways are mutually exclusive. In the other report, the calcium-modulated ROS
      GC1:GCAP1 signaling system has been discovered in mitral cells of the olfactory
      bulb. These findings raise the possibility that a common theme of calcium
      modulated ROS-GC signaling may be utilized in a wide variety of neurosensory
      cells. This idea is also supported from evolutionary and functional perspectives.

PMID- 11952085
TI  - Calcium-modulated membrane guanylate cyclase in synaptic transmission?
AB  - Rod outer segment guanylate cyclase 1 (ROS-GC1) is a pivotal enzyme for
      vertebrate phototransduction and the systematically growing evidence point to its
      connection with processes other than phototransduction within and outside the
      retina. ROS-GC1 activity is regulated by Ca2+ in two opposite modes. This
      regulation is indirect and occurs through Ca+-binding proteins. At nanomolar Ca2+
      concentrations, ROS-GC1 is activated by GCAPs and at micromolar Ca2+
      concentrations, by S100beta and neurocalcin. The former mode operates in
      phototransduction and the latter was proposed to play a role in synaptic
      activity. The last possibility was supported by findings of ROS-GC1 expression
      not only in various retinal layers other than photoreceptor outer segments but
      also outside the retina, in pineal gland and olfactory bulb. If ROS-GC1 indeed is
      to play a role in neurotransmission its expression must be colocalized with its
      Ca2+-dependent regulators and with possible targets of an increased cyclic GMP
      concentration, cyclic nucleotide-gated channels or cyclic GMP-dependent protein
      kinase, in synaptic regions. In this review these aspects of ROS-GC1 expression
      in retina, pineal gland and olfactory bulb are discussed.

PMID- 11952088
TI  - Retinal diseases linked with photoreceptor guanylate cyclase.
AB  - Inherited retinal dystrophies are the main causes of progressive visual
      impairment often leading to blindness. They represent a clinically and
      genetically heterogenous group of disorders. Continuously increasing body of
      evidence links retinal dystrophies to mutations in numerous genes. These genes
      code for retinal proteins of various function (phototransduction, visual cycle,
      transcription factors, structural and metabolic functions). Mutations in the gene
      coding for photoreceptor specific guanylate cyclase type 1, ROS-GC1, were found
      to be the cause for the type 1 Leber's congenital amaurosis (LCAI) and cone-rod
      dystrophy type 6 (CORD6). The LCA1-linked mutations are distributed over almost
      the entire ROS-GCI coding sequence but the CORD6-linked mutations are restricted
      to three positions, E786, R787 and T788, located within the putative ROS-GC1
      dimerization domain. A linkage between the biochemical effect of the mutation and
      its phenotypic manifestation was provided for only one LCA1 mutation, F514S. This
      was followed by biochemical analyses of the consequences of the CORD6-causing
      mutations. Here, an overview on the existing results and a discussion of the
      possible physiological implications are presented.

PMID- 11952089
TI  - Factors that affect regulation of cGMP synthesis in vertebrate photoreceptors and
      their genetic link to human retinal degeneration.
AB  - Cyclic GMP is essential for the ability of rods and cones to respond to the light
      stimuli. Light triggers hydrolysis of cGMP and stops the influx of sodium and
      calcium through the cGMP-gated ion channels. The consequence of this event is 2
      fold: first, the decrease in the inward sodium current plays the major role in an
      abrupt hyperpolarization of the cellular membrane; secondly, the decrease in the
      Ca2+ influx diminishes the free intracellular Ca2+ concentration. While the
      former constitutes the essence of the phototransduction pathway in rods and
      cones, the latter gives rise to a potent feedback mechanism that accelerates
      photoreceptor recovery and adaptation to background light. One of the most
      important events by which Ca2+ feedback controls recovery and light adaptation is
      synthesis of cGMP by guanylyl cyclase. Two isozymes of membrane photoreceptor
      guanylyl cyclase (retGC) have been identified in rods and cones that are
      regulated by Ca2+-binding proteins, GCAPs. At low intracellular concentrations of
      Ca2+ typical for light-adapted rods and cones GCAPs activate RetGC, but
      concentrations above 500 nM typical for dark-adapted photoreceptors turn them
      into inhibitors of retGC. A variety of mutations found in GCAP and retGC genes
      have been linked to several forms of human congenital retinal diseases, such as
      dominant cone degeneration, cone-rod dystrophy and Leber congenital amaurosis.

PMID- 11952090
TI  - Guanylyl cyclases in unicellular organisms.
AB  - Guanylyl cyclases in eukaryotic unicells were biochemically investigated in the
      ciliates Paramecium and Tetrahymena, in the malaria parasite Plasmodium and in
      the ameboid Dictyostelium. In ciliates guanylyl cyclase activity is calcium
      regulated suggesting a structural kinship to similarly regulated membrane-bound
      guanylyl cyclases in vertebrates. Yet, cloning of ciliate guanylyl cyclases
      revealed a novel combination of known modular building blocks. Two cyclase
      homology domains are inversely arranged in a topology of mammalian adenylyl
      cyclases, containing two cassettes of six transmembrane spans. In addition the
      protozoan guanylyl cyclases contain an N-terminal P-type ATPase-like domain.
      Sequence comparisons indicate a compromised ATPase function. The adopted novel
      function remains enigmatic to date. The topology of the guanylyl cyclase domain
      in all protozoans investigated is identical. A recently identified Dictyostelium
      guanylyl cyclase lacks the N-terminal P-type ATPase domain. The close functional
      relation of Paramecium guanylyl cyclases to mammalian adenylyl cyclases has been
      established by heterologous expression, respective point mutations and a series
      of active mammalian adenylyl cyclase/ Paramecium guanylyl cyclase chimeras. The
      unique structure of protozoan guanylyl cyclases suggests that unexpectedly they
      do not share a common guanylyl cyclase ancestor with their vertebrate congeners
      but probably originated from an ancestral mammalian-type adenylyl cyclase.

PMID- 11952091
TI  - Isoforms of NO-sensitive guanylyl cyclase.
AB  - By the formation of cGMP the NO-sensitive guanylyl cyclase plays a key role
      within the NO/cGMP signaling cascade involved in vascular regulation and
      neurotransmission. The prosthetic heme group of the enzyme acts as the NO sensor,
      and binding of NO induces conformational changes leading to an up to 200-fold
      activation of the enzyme. The unexpected fast dissociation half-life of NO of a
      few seconds is fast enough to account for the deactivation of the enzyme in
      biological systems. YC-1 and its analogues acting as NO sensitizers uncovered a
      new pharmacologically and conceivably physiologically relevant regulatory
      principle of the enzyme. Two existing isoforms of the heterodimeric guanylyl
      cyclase (alpha1beta1, alpha2beta1) are known that are functionally
      indistinguishable. Up to now, the NO-sensitive guanylyl cyclase has been
      considered as a soluble enzyme. However, recent evidence about the alpha2beta1
      isoform interacting with a PDZ domain of the postsynaptic scaffold protein PSD-95
      suggests that the alpha2 subunit directs a membrane association of this isoform.
      The interaction with PSD-95 locates the alpha2beta1 isoform in close proximity to
      the NO-generating NO synthase thereby enabling the NO sensor to respond to
      locally raised NO concentrations.

PMID- 11952092
TI  - The receptor-like properties of nitric oxide-activated soluble guanylyl cyclase
      in intact cells.
AB  - Soluble guanylyl cyclase (sGC) is the main receptor for nitric oxide (NO), and so
      mediates a wide range of effects (e.g. vasodilatation, platelet disaggregation
      and neural signalling) through the accumulation of cGMP and the engagement of
      various downstream targets, such as protein kinases and ion channels. Until
      recently, our understanding of sGC functioning has been derived exclusively from
      studies of the enzyme in tissue homogenates or in its purified form. Here, NO
      binds to the haem prosthetic group of sGC, triggering a conformational change and
      a large increase in catalytic activity. The potency (EC50) of NO appears to be
      about 100-200 nM. The rate of activation of sGC by NO is rapid (milliseconds)
      and, in the presence of excess substrate, cGMP is formed at a constant rate; on
      removal of NO, sGC deactivates slowly (seconds-minutes). Recent investigation of
      the way that sGC behaves in its natural environment, within cells, has revealed
      several key differences. For example, the enzyme exhibits a rapidly desensitizing
      profile of activity; the potency of NO is 45 nM for the minimally-desensitized
      enzyme but becomes higher with time, deactivation of sGC on removal of NO is 25
      fold faster than the fastest estimate for purified sGC. Overall, within cells,
      sGC behaves in a way that is analogous to the way that classical neurotransmitter
      receptors operate. The properties of cellular sGC have important implications for
      the understanding of NO-cGMP signalling. For example, the dynamics of the enzyme
      means that fluctuations in the rate of NO formation, even on subsecond time
      scale, will result in closely synchronized sGC activity in neighbouring cells;
      desensitization of sGC provides an economical way of generating a cellular cGMP
      signal and, in concert with phosphodiesterases, provides the basis for cGMP
      signal diversity, allowing different targets (outputs) to be selected from a
      common input (NO). Thus, despite exhibiting only limited molecular heterogeneity,
      cellular sGC functions in a way that introduces speed, complexity, and
      versatility into NO-cGMP signalling pathways.

PMID- 11952093
TI  - Soluble guanylate cyclases in the retina.
AB  - Soluble guanylate cyclase catalyzes the formation of cyclic GMP using GTP as
      substrate. It is now well established that soluble guanylate cyclase is highly
      activated by nitric oxide, and that many of the effects of nitric oxide on
      various cells and tissues are mediated through increased production of cyclic
      GMP. This review discusses the evidence for the presence of soluble guanylate
      cyclases in different classes of cells in vertebrate retina and the role of these
      enzymes in retinal physiology. It is concluded that the enzyme is present in
      nearly every class of cells in the retina and that it may be involved in signal
      transmission between some cells and in the modulation of signal transmission
      between others.

PMID- 11952096
TI  - Natriuretic peptide receptor: structure and signaling.
AB  - The ANP receptor is a single-transmembrane sequence receptor coupled to guanylate
      cyclase (GCase). It belongs to a family of GCase-coupled receptors that share a
      common overall molecular configuration. Collectively, theses GCase-coupled
      receptors belong to a larger family of single-transmembrane sequence receptors
      that include growth hormone and cytokine receptors. The signal transduction
      mechanism of these receptors has not been thoroughly understood. Receptor
      dimerization (or oligomerization) has been suggested as the mechanism. However,
      at least for the ANP receptor, dimerization has been seen to occur in the absence
      of the ligand, suggesting that an additional, as yet unknown effect of hormone
      binding is responsible for receptor activation. To understand the signaling
      mechanism, some of the functions and subsites of the ANP receptor critical for
      signaling have been identified, including the binding stoichiometry, receptor
      self-association, the juxtamembrane hinge structure containing a signature motif
      critical for GCase signaling, ANP-binding site residues, chloride-dependence of
      ANP binding, disulfide linkages, and glycosylation structures. These structures
      and the functional sites have been identified in the crystal structure of
      dimerized recombinant extracellular domain of the ANP receptor. The intracellular
      domain contains a kinase-homologous domain that regulates the activity of the
      GCase domain responding to ANP binding and also to binding of the allosteric
      effector ATP. Moreover, this regulatory role of the kinase-homologous domain is
      modulated by its own phosphorylated state. Although considerable data have been
      accumulated, the mechanism of ANP receptor signaling has not been well defined.
      Further studies are necessary to understand how ANP binds to the receptor, what
      conformational effect is caused by ANP binding, how this effect is transduced
      across the cell membrane, and how this transmembrane effect leads to stimulation
      of the GCase catalytic activity.

PMID- 11952094
TI  - Evolution of the membrane guanylate cyclase transduction system.
AB  - Almost four decades of research in the field of membrane guanylate cyclases is
      discussed in this review. Primarily, it focuses on the chronological development
      of the field, recognizes major contributions of the original investigators,
      corrects certain misplaced facts, and projects its future trend.

PMID- 11952097
TI  - Intracellular trafficking and metabolic turnover of ligand-bound guanylyl
      cyclase/atrial natriuretic peptide receptor-A into subcellular compartments.
AB  - Atrial natriuretic peptide (ANP) is the first described member of the natriuretic
      peptide hormone family. ANP elicits natriuretic, diuretic, vasorelaxant and
      antiproliferative effects, important factors in the control of blood pressure
      homeostasis. One of the principal loci involved in the regulatory action of ANP
      is the guanylyl cyclase-linked ANP-receptor which has been designated as NPRA,
      also referred to as GC-A, whose ANP-binding efficiency and guanylyl cyclase
      activity vary remarkably in different target tissues. However, the cellular and
      molecular basis of these activities and the functional expression and regulation
      of NPRA are not well understood. The mature form of receptor resides in the
      plasma membrane and consists of an extracellular ligand-binding domain, a single
      transmembrane-spanning region, and intracellular protein kinase-like homology and
      guanylyl cyclase catalytic domains. In this review, emphasis has been placed on
      the interaction ofANP with NPRA, the ligand-mediated endocytosis, trafficking,
      and subcellular distribution of ligand-receptor complexes from cell surface to
      the intracellular compartments. Furthermore, it is implicated that after
      internalization, the ANP/NPRA complexes dissociate into the subcellular
      compartments and a population of receptor recycles back to the plasma membrane.
      This is an interesting area of research in the natriuretic peptide receptor field
      because there is currently debate over whether ANP/NPRA complexes internalize at
      all or whether cell utilizes some other mechanisms to release ANP from the bound
      receptor molecules. Indeed, controversy exist since it has been previously
      reported by default that among the three natriuretic peptide receptors only NPRC
      internalizes with bound ligand. Hence, from a thematic standpoint it is clearly
      evident that there is a current need to review this subject and provide a
      consensus forum that establishes the cellular trafficking, sequestration and
      processing of ANP/NPRA complexes in intact cells. Towards this aim the cellular
      life-cycle of NPRA will be described in the context ofANP-binding,
      internalization, metabolic processing, and/or inactivation, down-regulation, and
      degradation of ligand-receptor complexes in model cell systems.

PMID- 11952095
TI  - Biochemistry and physiology of the natriuretic peptide receptor guanylyl
      cyclases.
AB  - Guanylyl cyclases (GC) exist as soluble and particulate, membrane-associated
      enzymes which catalyse the conversion of GTP to cGMP, an intracellular signalling
      molecule. Several membrane forms of the enzyme have been identified up to now.
      Some of them serve as receptors for the natriuretic peptides, a family of
      peptides which includes atrial natriuretic peptide (ANP), brain natriuretic
      peptide (BNP) and C-type natriuretic peptide (CNP), three peptides known to play
      important roles in renal and cardiovascular physiology. These are transmembrane
      proteins composed of a single transmembrane domain, a variable extracellular
      natriuretic peptide-binding domain, and a more conserved intracellular kinase
      homology domain (KHD) and catalytic domain. GC-A, the receptor for ANP and BNP,
      also named natriuretic peptide receptor-A or -1 (NPR-A or NPR- 1), has been
      studied widely. Its mode of activation by peptide ligands and mechanisms of
      regulation serve as prototypes for understanding the function of other
      particulate GC. Activation of this enzyme by its ligand is a complex process
      requiring oligomerization, ligand binding, KHD phosphorylation and ATP binding.
      Gene knockout and genetic segregation studies have provided strong evidence for
      the importance of GC-A in the regulation of blood pressure and heart and renal
      functions. GC-B is the main receptor for CNP, the latter having a more paracrine
      role at the vascular and venous levels. The structure and regulation of GC-B is
      similar to that of GC-A. This chapter reviews the structure and roles of GC-A and
      GC-B in blood pressure regulation and cardiac and renal pathophysiology.

PMID- 11952098
TI  - Structure and function of the heat-stable enterotoxin receptor/guanylyl cyclase
      C.
AB  - Guanylyl cyclase C (GC-C) was found to function as the principal receptor for
      heat-stable enterotoxins (STa), major causative factors in E. coli-induced
      secretory diarrhea. GC-C is enriched in intestinal epithelium, but was also
      detected in other epithelial tissues. The enzyme belongs to the family of
      receptor guanylyl cyclases, and consists of an extracellular receptor domain, a
      single transmembrane domain, a kinase homology domain, and a catalytic domain. GC
      C is modified by N-linked glycosylation and, at least in the small intestine, by
      proteolysis, resulting in a STa receptor that is coupled non-covalently to the
      intracellular domain. So far two endogenous ligands of mammalian GC-C have been
      identified i.e. the small cysteine-rich peptides guanylin and uroguanylin. The
      guanylins are released in an auto- or paracrine fashion into the intestinal lumen
      but may also function as endocrine hormones in gut-kidney communication and as
      regulators of ion transport in extra-intestinal epithelia. They are thought to
      activate GC-C by inducing a conformational change in the extracellular portion of
      the homotrimeric GC-C complex, which allows two of the three intracellular
      catalytic domains to dimerize and form two active catalytic clefts. In the
      intestine, activation of GC-C results in a dual action: stimulation of Cl and
      HCO3 secretion, through the opening of apical CFTR Cl channels; and inhibition of
      Na absorption, through blockade of an apical Na/H exchanger. The principal
      effector of the GC-C effect on ion transport is cGMP dependent protein kinase
      type II, which together with GC-C and the ion transporters, may form a
      supramolecular complex at the apical border of epithelial cells.

PMID- 11952099
TI  - Ultracytochemistry as a tool for the study of the cellular and subcellular
      localization of membrane-bound guanylate cyclase (GC) activity. Applicability to
      both receptor-activated and receptor-independent GC activity.
AB  - Membrane-bound guanylate cyclase activity was detected by ultracytochemistry at
      the electron microscope level in several mammalian tissues. The technique used in
      these studies allows the detection of active enzyme at the membrane site where it
      is located. In a few cases, such as normal and regenerating peripheral nerves and
      placenta, membrane-bound guanylate cyclase could be detected in the absence of
      stimulators of enzyme activity. However, in the majority of these studies
      membrane-bound guanylate cyclase was investigated following stimulation with
      natriuretic peptides, guanylin, or the Ca2+ sensor proteins, S100B and S100A1. In
      general, membrane-bound guanylate cyclase was localized to plasma membranes, in
      accordance with the functional role of this enzyme. Yet, in secretory cells the
      enzyme activity was localized on intracellular membranes, suggesting a role of
      membrane-bound guanylate cyclase in secretory processes. Finally, S100B and
      S100A1 were found to colocalize with membrane-bound guanylate cyclase on
      photoreceptor disc membranes and to stimulate enzyme activity at these sites in
      dark-adapted retinas in a Ca2+-dependent manner. The results of these analyses
      are discussed in relation to the proposed functional role(s) of this enzyme.

PMID- 11952101
TI  - 'Real' epidemiology of varicose veins and chronic venous diseases: the San
      Valentino Vascular Screening Project.
AB  - The aim of this study was to evaluate the prevalence and incidence of venous
      diseases and the role of concomitant/risk factors for varicose veins (VV) or
      chronic venous insufficiency (CVI). The study was based in San Valentino in
      Central Italy and was a real whole-population study. The study included 30,000
      subjects in eight villages/towns evaluated with clinical assessment and duplex
      scanning. The global prevalence of VV was 7%; for CVI, the prevalence was 0.86%
      with 0.48% of ulcers. Incidence (new cases per year) was 0.22% for VV and 0.18%
      for CVI; 34% of patients with venous disease had never been seen or evaluated.
      The distribution of VV and CVI in comparison with duplex-detected incompetence
      (DI) indicates that 12% of subjects had only VV (no DI), 2% had DI but no VV,
      7.5% had DI associated with VV, 2% apparent CVI without DI, 3% DI only (without
      CVI), and 1.6% both CVI and DI. VV associated with DI are rapidly progressive and
      CVI associated with DI often progresses to ulceration (22% in 6 years). VV
      without significant DI (3%) and venous dilatation without DI tend to remain at
      the same stage without progression for a lengthy time. New cases per year appear
      to have a greater increase in the working population (particularly CVI) possibly
      as a consequence of trauma during the working period. In older age (>80 years),
      the incidence of CVI tends to decrease. Ulcers increase in number with age. Only
      22% of ulcers can be defined as venous (due to venous hypertension, increased
      ambulatory venous pressure, shorter refilling time, obstruction and DI). Medical
      advice for VV or CVI is requested in 164 subjects of 1,000 in the population. In
      39 of 1,000, there is a problem but no medical advice is requested and in only 61
      of 1,000, the venous problem is real. In VV in 78% of limbs, there is only
      reflux, in 8% only obstruction, and in 14% both. In CVI, 58% of limbs have
      reflux, 23% obstruction, and 19% both. In conclusion, VV and CVI are more common
      with increasing age. The increase with age is linear. There was no important
      difference between males and females. These results are the basis for future
      real, whole population studies to evaluate VV and CVI.

PMID- 11952102
TI  - Elastic fibers in saphenous varicose veins.
AB  - The purpose of this study is to describe the elastic fibers of varicose
      collateral saphenous veins. Sections were obtained from venous segments of
      patients with essential varices and stained with resorcin-fuchsin for elastic
      system fibers and analyzed with laser scanning microscopy after Evans blue
      staining. Vein portions (270 microm) were classified as without thickening, with
      a cushion, or with a diffuse thickening. The elastic material density of the
      intima (Dei) and media (Dem) were tested for differences by the Kruskal-Wallis
      test. Diffuse thickening (87.1+/-8.6 microm) represents 54.5% of the segment.
      Cushion occupies 23.5% with 42.4+/-4.66 microm. The elastic network present in
      the cushion is formed by elastic fibers of different diameters that branch into
      delicate oxytalan fibers in association with the smooth muscle cells. The diffuse
      thickening elastic network varies from elastic lamellae and delicate oxytalan
      fibers related to the intima smooth muscle cell bundles to fragmented elastic
      fibers in the collagenous areas. Dei increases as the intima enlarges (10.19,
      14.63, and 16.01, respectively to without thickening, cushion, diffuse
      thickening). In the media, the elastic network encircles the circular muscle
      bundles connecting them to the elastic internal lamina and to elastic fibers in
      the adventitia. Smooth muscle cells were coiled by numerous oxytalan fibers and
      the elastic fibers are irregular and fragmented. In the sclerotic portions, the
      elastic fibers are sparse. No correlation was found between Dei and Dem. The
      important thickening of varicose vein intima shows increasing quantities of
      elastic material formerly associated with smooth muscle cells. In the media, the
      elastic network around smooth muscle cell bundles is disrupted and the Dem
      diminishes as the media becomes sclerotic.

PMID- 11952100
TI  - Photoreceptor specific guanylate cyclases in vertebrate phototransduction.
AB  - Two membrane bound guanylate cyclases are expressed in vertebrate photoreceptor
      cells. They serve a key function in photoreceptor physiology as they synthesize
      the intracellular transmitter of photoexcitation guanosine 3',5'-cyclic
      monophosphate (cGMP). Both cyclases named ROS-GC1 and ROS-GC2 form a subclass of
      membrane bound cyclases and differ in many aspects from hormone peptide receptor
      guanylate cyclases. One unique feature is their regulation by three small Ca2+
      binding proteins called GCAPs. These regulatory proteins sense changes in the
      cytoplasmic Ca2+-concentration [Ca2+] during illumination and activate ROS-GCs
      when the [Ca2+] decreases below the value in a dark adapted cell of 500-600 nM.
      Recent work has identified the target regions of GCAP-1 in ROS-GC1. In addition
      to GCAPs several other proteins including aktin, tubulin, a glutamic-acid-rich
      protein and a GTPase accelerating protein (RGS9) were found to interact with ROS
      GC1 and probably form a multiprotein complex.

PMID- 11952104
TI  - Long-term follow-up after coronary stent implantation in patients with coronary
      artery disease.
AB  - Prospective randomized trials of coronary stenting in patients with coronary
      artery disease have shown a reduced incidence of cardiac events. However, little
      is known of the late outcome of patients treated with coronary stenting. The
      purpose of this study was to evaluate the relatively long-term clinical outcomes
      (3 to 6 years) of patients treated with successful coronary stenting. The long
      term clinical outcome was studied in 101 consecutive patients (78 males and 23
      females) who had undergone successful coronary stent implantation for coronary
      artery disease in our hospital from October 1994 to September 1997. During a
      follow-up period of 48.9+/-9.5 months (range, 6-73 months), cardiac events were
      documented in 37 patients. The rate of survival free of cardiac events was 67% at
      3 years. Multiple logistic regression analysis showed that ACC/AHA lesion type
      and residual percent diameter stenosis greater than 20% after stenting were the
      significant explanatory factors of adverse cardiac events. Long-term clinical
      outcome in patients with coronary artery disease treated with successful coronary
      stenting was influenced by the ACC/AHA lesion type of stented lesion and residual
      percent diameter stenosis after stent implantation.

PMID- 11952103
TI  - Coronary artery disease and periodontal disease: is there a link?
AB  - BACKGROUND: Cardiovascular disease is the number one killer worldwide. The so
      called classic risk factors of coronary heart disease do not account for all of
      its clinical and epidemiological features. Recent evidence suggests that certain
      infections, among them dental infections and in particular periodontal disease,
      are involved in the pathogenesis of coronary artery disease. AIM: To evaluate the
      association between periodontal disease and coronary artery disease. PATIENTS AND
      METHODS: Fifty patients referred for diagnostic coronary angiography were
      assessed for periodontal disease. All patients underwent a thorough physical
      examination, routine laboratory testing, cardiac evaluation and dental
      examination which included pantomography x-ray evaluation. RESULTS: Pantomography
      x-rays and coronary angiograms of the participants were scored blindly by a
      dentist and cardiologists respectively. The association between periodontal
      disease and coronary atheromatosis remained significant after adjustment for age,
      smoking, blood lipids, body mass index, hypertension and the presence of
      diabetes. IMPLICATIONS: Periodontal disease was still significantly associated
      after all the known risk factors were accounted for. The implication here is that
      periodontal disease could be a potential risk factor for heart disease by
      predisposing the individual to chronic low-grade infections. If so, then dental
      health becomes an important parameter for medical health.

PMID- 11952105
TI  - Fibrinolytic parameters and lipoprotein(a) in young women with myocardial
      infarction.
AB  - Impaired fibrinolysis and elevated lipoprotein(a) (Lp[a]) are possible nonclassic
      risk factors for myocardial infarction (MI) at young age. The fibrinolytic system
      in young women with MI has not been evaluated yet and the role of Lp(a) is still
      controversial. The authors determined fibrinolytic parameters and Lp(a) in
      premenopausal women (mean age 42+/-3 years, n = 22) 0.5 to 6 (mean 3.5) years
      after MI, who were all without severe classic risk factors and had an otherwise
      low risk for MI. Elevated levels of tissue type plasminogen activator (t-PA) (p<
      0.05) were measured in comparison to 52 age-matched controls; no difference was
      found in plasminogen activator inhibitor, plasminogen, fibrinogen, euglobulin
      clotting time and D-dimers. Significantly more MI patients had Lp(a) levels
      greater than 300 mg/L compared to controls (36% vs 13.5%, p< 0.05). The
      combination of elevated Lp(a), mild hyperlipidemia, and nonsevere smoking was
      found in 62.5% of MI patients who had elevated levels of Lp(a), in 23% of all
      women with MI, and in none of the controls. Elevated t-PA is probably only a
      marker of increased risk of MI, whereas elevated Lp(a) probably has a causative
      role. A combination of elevated Lp(a), hyperlipidemia, and nonsevere smoking
      seems to be a high-risk profile, relatively common in young women with MI.

PMID- 11952106
TI  - Aortic valve calcification: its significance and limitation as a marker for
      coronary artery disease.
AB  - Aortic valve calcification (AVC) is correlated with atherosclerotic risk factors;
      however, its significance remains largely unknown. The aim of this study was to
      investigate whether AVC detected by transthoracic echocardiography can be a
      useful marker for the identification of significant coronary artery disease
      (CAD), particularly in elderly patients. The study included 432 consecutive
      patients with suspected CAD who were admitted for the first time for coronary
      angiography. Two-dimensional transthoracic echocardiography and selective
      coronary angiography were performed in all patients. Aortic valve calcification
      was defined as bright dense echoes of > 1 mm on one or more cusps and decreased
      mobility of the involved cusp. Aortic valve calcification was detected in 64 of
      the 337 patients with significant CAD, but only in 9 of 95 cases with normal or
      mildly stenotic coronary arteries (19% vs 9%, p < 0.001). The severity of
      coronary artery disease (defined as the number of obstructed vessels) was not
      related to the presence of AVC (p > 0.05). Stepwise multiple logistic regression
      analysis of the study patients revealed only age (p=0.003, odds ratio= 1.56) and
      AVC (p<0.001, odds ratio = 2.03) as independent predictors of CAD. When the study
      population was divided into two groups as those below (n = 338) and above (n =
      94) 75 years old, AVC failed to be a predictor of CAD in those >75 years old (p >
      0.05, odds ratio = 0.8) while it remained the most significant predictor of CAD
      (p<0.001, odds ratio=2.19 in patients aged <75 years. In conclusion, detection of
      AVC by transthoracic echocardiography may be a useful noninvasive marker for
      identification of significant CAD in patients younger than 75 years old. Its
      clinical usefulness is limited in elderly patients.

PMID- 11952107
TI  - Haziness on coronary angiogram after percutaneous transluminal coronary
      angioplasty evaluated with angioscopy.
AB  - Coronary angiograms obtained after percutaneous transluminal coronary angioplasty
      are often hazy due to uneven distribution of contrast medium at the angioplasty
      site, In this study, structural changes resulting in haziness after percutaneous
      transluminal coronary angioplasty were identified angioscopically. The affected
      coronary arteries of 35 patients who underwent successful percutaneous
      transluminal coronary angioplasty were examined with angioscopy. Coronary
      angioscopic examination of the sites subjected to percutaneous transluminal
      coronary angioplasty revealed large surface disruptions in 17 cases, small
      surface disruptions in four cases, and thrombi in 24 cases. Angiographic haziness
      was recognized in 24 of 35 patients after percutaneous transluminal coronary
      angioplasty. Haziness on angiography was more significant in patients who
      exhibited large surface disruption (88% vs 50%, p < 0.05), and was significantly
      greater in patients who exhibited white thrombus (100% vs 56%, p<0.05). Moreover,
      it appears that percutaneous transluminal coronary angioplasty-induced large
      surface disruption and white thrombus likely play an important role in increasing
      haziness.

PMID- 11952108
TI  - Ultrasonic correlates of common carotid atherosclerosis in patients with coronary
      artery disease.
AB  - Increased intima-media thickness and plaque development in the extracranial
      carotid arteries reportedly correlate well with the prevalence of coronary artery
      diseases. The location of these atherosclerotic lesions in the carotid artery
      varies with age in patients with coronary artery atherosclerosis. Intima-media
      thickness, plaque, and calcification in the common carotid artery and bifurcation
      were assessed with high-resolution B-mode ultrasonography. Forty patients with
      severe atherosclerosis of the coronary artery and 56 healthy control subjects
      with no risk factors for coronary atherosclerosis were included in this study.
      The subjects were divided into a middle-age group (40-59 yr) and an old-age group
      (60-79 yr). In both groups, the intimamedia thickness in the patients was
      significantly higher than that in the controls. Intima-media thickness of at
      least 0.7 mm in the middle-age group and at least 1.0 mm in the old-age group was
      specific and positively predictive of coronary artery disease. Plaque (> 1.0 mm)
      and calcification were more significant in patients than in controls. In the
      middle-age group, intimamedia thickness in the common carotid artery was
      correlated with coronary atherosclerotic severity. Conversely, in the old-age
      group, the presence of plaque and calcification at the bifurcation was correlated
      with coronary atherosclerotic severity. The characteristic manifestation of the
      atherosclerotic lesion in the carotid artery varied with age in patients with
      coronary artery disease.

PMID- 11952110
TI  - Clinical, bacteriologic and echocardiographic evaluation of infective
      endocarditis in Ankara, Turkey.
AB  - This study consists of a retrospective evaluation of microbiologic,
      echocardiographic, and clinical characteristics of patients with infective
      endocarditis seen at Turkiye Yuksek Ihtisas and SSK Ihtisas Hospitals during the
      previous 5 years to provide a basis for comparison with other series. The study
      was performed retrospectively. The mean age of the patient population, which
      consisted of 74 cases, was considerably low (24.6+/-12.3 yr). The majority of the
      patients were male (male/female = 1.96). Rheumatic valvular disease was the
      underlying cardiac pathosis in 66% of the cases. Congestive heart failure,
      embolic episodes, and mortality were more frequent among those with
      echocardiographically demonstrable cardiac vegetations. The microbiologic profile
      was considerably different from that of other series. In addition, this
      population showed a higher rate of congestive heart failure compared to other
      series. The patients with infective endocarditis in this series in the previous 5
      years were found to be different from series reported from western countries.

PMID- 11952109
TI  - Association of carotid artery intima-media thickness with complex aortic
      atherosclerosis in patients with recent stroke.
AB  - This study was undertaken to determine whether carotid intima-media thickness can
      predict complex aortic atherosclerosis. A retrospective review was conducted of
      64 consecutive patients who underwent transesophageal echocardiography and
      carotid ultrasonography for evaluation of recent ischemic stroke at MCP Hahnemann
      University, Medical College of Pennsylvania Hospital between January 1, 1999, and
      December 31, 1999. The mean age was 65+/-14 years and 59% of the patients were
      women. Thirty-nine patients (61%) had carotid atherosclerosis (defined as an
      intima-media thickness > or =1 mm) and seven patients (11%) had complex aortic
      atherosclerosis (defined as the presence of protruding atheroma > or =4 mm thick,
      mobile atherosclerotic debris, or plaque ulceration in any aortic segment by
      transesophageal echocardiography). Compared to patients without complex aortic
      atherosclerosis, patients with complex aortic atherosclerosis were more likely to
      have hypercholesterolemia (19% vs 57%, p = 0.05) and a carotid intima-media
      thickness of 2 mm or greater (35% vs 86%, p = 0.02). A carotid intima-media
      thickness of 2 mm or more had 86% sensitivity, 65% specificity, 23% positive
      predictive value, 97% negative predictive value, 2.5 positive likelihood ratio,
      and 0.22 negative likelihood ratio for the diagnosis of complex aortic
      atherosclerosis. Carotid intimamedia thickness measurement can be used to
      noninvasively estimate the probability of complex aortic atherosclerosis. A
      carotid intima-media thickness less than 2 mm makes complex aortic
      atherosclerosis very unlikely.

PMID- 11952111
TI  - The chronic effect of rilmenidine on heart rate variability in patients with mild
      hypertension.
AB  - The purpose of this study was to evaluate the chronic effect of rilmenidine on
      time domain indexes of heart rate variability in patients with mild hypertension.
      Twenty patients (12 males, eight females; mean age, 47 yr; age range, 38-55 yr),
      with untreated and newly diagnosed mild hypertension were studied. There was no
      evidence of diseases other than hypertension. All patients received 1 mg of
      rilmenidine once daily. If the diastolic blood pressure was still greater than 90
      mm Hg after 4 weeks of active treatment, the dose was increased to 2 mg once
      daily. Twenty-four hour ambulatory electrocardiograms were recorded before, and 4
      and 12 weeks after the start of therapy. Time domain parameters of heart rate
      variability were calculated. Rilmenidine therapy determined a marked decrease in
      blood pressure. At 4 weeks, rilmenidine induced a significant reduction in
      systolic and diastolic blood pressure and a further reduction was observed after
      12 weeks. At 4 and 12 weeks, time domain parameters of heart rate variability and
      heart rate were not significantly different in the data obtained before therapy.
      In conclusion, this study demonstrated that the administration of rilmenidine to
      patients with mild essential hypertension induced significant reductions in blood
      pressure, without any significant changes in time domain parameters of heart rate
      variability.

PMID- 11952112
TI  - Spontaneous coronary artery dissection--a case report and review of the
      literature.
AB  - Spontaneous coronary artery dissection remains an extremely rare cause of
      myocardial ischemia and infarction. The clinical picture of spontaneous coronary
      dissection is often sudden cardiac death or fatal myocardial infarction. This
      report describes a previously healthy woman who developed spontaneous coronary
      artery dissection. She presented with sudden onset of chest pain and was found to
      have evidence of acute inferior wall myocardial infarction. She received
      streptokinase immediately after admission to the coronary care unit. Coronary
      angiographic studies revealed a linear dissection involving the proximal and mid
      segments of the right coronary artery.

PMID- 11952113
TI  - Irreversible myocardial damage after coronary air embolism--a case report.
AB  - This case report describes the complication of an air embolism in the right
      coronary artery that developed during coronary angiography in a patient with
      acute anterior myocardial infarction. Follow-up left ventriculography, 4 months
      later, showed irreversible inferior wall damage. Incomplete aspiration of the
      angiographic catheter was the cause of this complication and should be avoided.

PMID- 11952114
TI  - Ipsilateral intracerebral hemorrhage following carotid stent-assisted
      angioplasty: a manifestation of hyperperfusion syndrome--a case report.
AB  - A case of hyperperfusion syndrome manifested as intracerebral hemorrhage
      following carotid stent-assisted angioplasty while using intravenous abciximab is
      described. Review of literature regarding hyperperfusion syndrome in patients
      undergoing carotid artery revascularization is presented. Possible mechanisms of
      hyperperfusion and the role of arterial hypertension, anticoagulation, and
      antiplatelet treatment in the genesis of hyperperfusion syndrome are discussed.
      Widening use of percutaneous carotid revascularization necessitates physicians'
      awareness of early recognition of this complication.

PMID- 11952115
TI  - Successful surgical resection of a muscular bridge in a patient with
      nonobstructive hypertrophic cardiomyopathy--a case report.
AB  - The authors report a case of myocardial bridging associated with nonobstructive
      hypertrophic cardiomyopathy and severe intractable chest pain that was relieved
      by surgical resection of the muscular bridge. Surgical resection of a myocardial
      bridge may be considered in patients with refractory symptoms that can clearly be
      attributed to muscular bridge.

PMID- 11952116
TI  - Traumatic tricuspid insufficiency--a case report.
AB  - Traumatic tricuspid insufficiency following blunt chest trauma, although an
      uncommon entity, has been reported more frequently over the past 2 decades.
      Increased physician awareness of the possibility of myocardial trauma accompanied
      by proper clinical evaluation and follow-up are the keys to a successful outcome
      regardless of whether a medical or surgical approach to treatment is initially
      selected. Early surgical correction has become the preferred treatment in most
      instances and may be influenced by clinical status and other associated comorbid
      conditions. A patient with a combination of myocardial contusion, valve
      laceration, and papillary muscle rupture is presented.

PMID- 11952117
TI  - Diffuse neonatal hemangiomatosis without cutaneous lesions in an adult--a case
      report.
AB  - Diffuse neonatal hemangiomatosis (DNH) is a rare disorder that first presents
      with multiple cutaneous and visceral hemangiomas during the neonatal period and
      has a high mortality rate. The authors report a long-term survivor of DNH who
      presented with multiple visceral hemangiomas without cutaneous lesions. Vascular
      endothelial growth factor (VEGF) may play an important role in tumor progression.

PMID- 11952118
TI  - Primary cardiac lymphoma--a case report.
AB  - Primary cardiac lymphoma, which is very rare, is generally regarded to have a
      poor prognosis. A case of a 69-year-old man with primary cardiac lymphoma
      diagnosed by antemortem examination is reported. A computed tomography scan of
      the chest demonstrated a huge right atrial mass with invasion into the other
      chambers. No mediastinal lymphadenopathy was detected. Cytologic analysis of
      pericardial effusion revealed diffuse large B-cell type non-Hodgkin malignant
      lymphoma. The patient died on the 18th day of chemotherapy (cyclophosphamide,
      hydroxydaunomycin, oncovin, and prednisone) due to low-output syndrome and
      multiple organ failure. At autopsy, massive gray-white tumor almost occupied the
      right atrium and invaded the right inferior lobe of the lung. Although prognosis
      of primary cardiac lymphoma remains poor, early diagnosis may improve the
      prognosis.

PMID- 11952119
TI  - Regarding "Rapid clot formation and abnormal fibrin structure in a symptomatic
      patient taking fenfluramine--a case report".

PMID- 11952120
TI  - MST12 regulates infectious growth but not appressorium formation in the rice
      blast fungus Magnaporthe grisea.
AB  - In the rice blast fungus Magnaporthe grisea, a mitogen-activated protein kinase
      gene, PMK1, is known to regulate appressorium formation and infectious hyphae
      growth. Since PMK1 is homologous to the FUS3 and KSS1 genes that regulate the
      transcription factor STE12 in yeast, we functionally characterized the STE12
      homologue in M. grisea (MST12). A polymerase chain reaction-based approach was
      used to isolate the MST12 gene that is homologous to yeast STE12. Four mst12
      deletion mutants were isolated by gene replacement. No obvious defect in
      vegetative growth, conidiation, or conidia germination was observed in mst12
      mutants. However, mst12 mutants were nonpathogenic on rice and barley leaves. In
      contrast to pmk1 mutants that did not form appressoria, mst12 mutants produced
      typical dome-shaped and melanized appressoria. However, the appressoria formed by
      mst12 mutants failed to penetrate onion epidermal cells. When inoculated through
      wound sites, mst12 mutants failed to cause spreading lesions and appeared to be
      defective in infectious growth. These data indicate that MST12 may function
      downstream of PMK1 to regulate genes involved in infectious hyphae growth. A
      transcription factor or factors other than MST12 must exist in M. grisea and
      function downstream from PMK1 for appressorium formation.

PMID- 11952121
TI  - Efficient infection of Nicotiana benthamiana by Tomato bushy stunt virus is
      facilitated by the coat protein and maintained by p19 through suppression of gene
      silencing.
AB  - Tomato bushy stunt virus (TBSV) is one of few RNA plant viruses capable of moving
      systemically in some hosts in the absence of coat protein (CP). TBSV also encodes
      another protein (p19) that is not required for systemic movement but functions as
      a symptom determinant in Nicotiana benthamiana. Here, the role of both CP and p19
      in the systemic spread has been reevaluated by utilizing transgenic N.
      benthamiana plants expressing the movement protein (MP) of Red clover necrotic
      mosaic virus and chimeric TBSV mutants that express CP of Turnip crinkle virus.
      Through careful examination of the infection phenotype of a series of mutants
      with changes in the CP and p19 genes, we demonstrate that both of these genes are
      required for efficient systemic invasion of TBSV in N. benthamiana. The CP likely
      enables efficient viral unloading from the vascular system in the form of
      assembled virions, whereas p19 enhances systemic infection by suppressing the
      virus-induced gene silencing.

PMID- 11952122
TI  - Mutation of three cysteine residues in Tomato yellow leaf curl virus-China C2
      protein causes dysfunction in pathogenesis and posttranscriptional gene-silencing
      suppression.
AB  - The nuclear localized C2 protein of the monopartite begomovirus Tomato yellow
      leaf curl virus-China (TYLCV-C) contributes to viral pathogenicity. Here, we have
      investigated TYLCV-C C2 protein domains that play a role in the phenotype.
      Alignment of the C2 protein with 67 homologues from monopartite and bipartite
      begomoviruses revealed that a putative zinc-finger motif C36-X1-C38-X7-C46-X6-H53
      X4-H58C59 and four potential phosphorylation sites (T52, S61, Y68, and S74) are
      highly conserved. When expressed from a Potato virus X (PVX) vector, TYLCV-C C2
      protein mutants C2-T52M, C2-H58S, C2-C59S, C2-S61R, and C2-S74D, like the wild
      type C2 protein, induced local necrotic ringspots and systemic necrosis in
      Nicotiana benthamiana plants. Mutants C2-H53P and C2-Y68D produced irregular
      necrotic lesions on inoculated leaves that were distinct from the wild-type
      phenotype. In contrast, mutants C2-C36R, C2-C38N, and C2-C46I induced chlorosis
      and mosaic symptoms rather than necrosis. We demonstrate that TYLCV-C C2, like
      its counterpart in the bipartite begomovirus African cassava mosaic virus,
      mediates suppression of posttranscriptional gene silencing (PTGS). Moreover, the
      individual mutations C36R, C38N, and C46I abolished the ability of C2 protein to
      suppress PTGS. These results suggest that the three cysteine residues within the
      putative zinc-finger motif are essential for C2 protein to induce necrosis and to
      act as a suppressor of PTGS.

PMID- 11952123
TI  - Differential expression patterns of an acidic chitinase and a basic chitinase in
      the root nodule of Elaeagnus umbellata.
AB  - Two cDNA clones encoding chitinase were isolated from a root nodule cDNA library
      of Elaeagnus umbellata by the hybridization-competition method. The two clones,
      EuNOD-CHT1 and EuNOD-CHT2, encode for 335 and 317 amino acid residues with the
      molecular mass of mature proteins being 33.3 and 31.1 kDa, respectively. The two
      chitinases showed similar protein structures consisting of four domains:
      hydrophobic signal peptide domain, cysteine-rich chitin-binding domain, hinge
      domain, and catalytic domain. The EuNOD-CHT1 gene showed similar expression
      levels in root nodules and leaves, with no detection of transcripts in the roots.
      The EuNOD-CHT2 gene was expressed at similarly high levels in the roots and root
      nodules, but at a very low level in the leaves. In situ hybridization showed that
      EuNOD-CHT1 transcripts were strongly detected in the meristem zone, but weakly
      detected in the outer cortex layer of the root nodule and in the uninfected cells
      of the fixation zone. On the other hand, EuNOD-CHT2 transcripts were strongly
      detected in the infected cells of the fixation zone and central vascular system,
      but weakly detected in the senescence zone. Our results suggest that the two
      chitinases may play different biological roles in the root nodule. EuNOD-CHT2 may
      be involved in a defense response against internal symbionts, external pathogens,
      or both, while EuNOD-CHT1 may be involved in normal plant development as well as
      in a defensive role against external pathogens.

PMID- 11952124
TI  - Localization of melanin in conidia of Alternaria alternata using phage display
      antibodies.
AB  - Melanins derived from 1,8-dihydroxynaphthalene (DHN) are important for the
      pathogenicity and survival of fungi causing disease in both plants and animals.
      However, precise information on their location within fungal cell walls is
      lacking. To obtain antibodies for the immunocytochemical localization of melanin,
      83 phage antibodies binding to 1,8-DHN were selected from a naive semisynthetic
      single-chain Fv (scFv) phage display library. Sequence analysis of the heavy
      chain binding domains of 17 antibodies showed a high frequency of positively
      charged amino acids. One antibody, designated M1, was characterized in detail. M1
      bound specifically to 1,8-DHN in competitive inhibition enzyme-linked
      immunosorbent assays, showing no cross-reaction with nine structurally related
      phenolic compounds. Epitope recognition required two hydroxyl groups in a 1,8
      configuration. M1 also bound to naturally occurring melanin isolated from mycelia
      of Alternaria alternata, suggesting that epitopes remain accessible in
      polymerized melanin. Transmission electron microscopy-immunogold labeling, using
      M1 in the form of soluble scFv fragments, showed that melanin was located in the
      septa and outer (primary) walls of wild-type A. alternata conidia, but not those
      of an albino mutant, AKT88-1. The M1 antibody provides a new tool for detecting
      melanized pathogens in plant and animal tissues and for precisely mapping the
      distribution of the polymer within spores, appressoria, and hyphae.

PMID- 11952125
TI  - Rhizobium tropici genes involved in free-living salt tolerance are required for
      the establishment of efficient nitrogen-fixing symbiosis with Phaseolus vulgaris.
AB  - Characterization of nine transposon-induced mutants of Rhizobium tropici with
      decreased salt tolerance (DST) allowed the identification of eight gene loci
      required for adaptation to high external NaCl. Most of the genes also were
      involved in adaptation to hyperosmotic media and were required to overcome the
      toxicity of LiCl. According to their possible functions, genes identified could
      be classified into three groups. The first group included two genes involved in
      regulation of gene expression, such as ntrY, the sensor element of the bacterial
      ntrY/ntrX two-component regulatory system involved in regulation of nitrogen
      metabolism, and greA, which encodes a transcription elongation factor. The second
      group included genes related to synthesis, assembly, or maturation of proteins,
      such as alaS coding for alanine-tRNA synthetase, dnaJ, which encodes a molecular
      chaperone, and a nifS homolog probably encoding a cysteine desulfurase involved
      in the maturation of Fe-S proteins. Genes related with cellular build-up and
      maintenance were in the third group, such as a noeJ-homolog, encoding a mannose-1
      phosphate guanylyltransferase likely involved in lipopolysaccharide biosynthesis,
      and kup, specifying an inner-membrane protein involved in potassium uptake.
      Another gene was identified that had no homology to known genes but that could be
      conserved in other rhizobia. When inoculated on Phaseolus vulgaris growing under
      nonsaline conditions, all DST mutants displayed severe symbiotic defects: ntrY
      and noeJ mutants were impaired in nodulation, and the remaining mutants formed
      symbiosis with very reduced nitrogenase activity. The results suggest that
      bacterial ability to adapt to hyperosmotic and salt stress is important for the
      bacteroid nitrogen-fixing function inside the legume nodule and provide genetic
      evidence supporting the suggestion that rhizobia face severe environmental
      changes after their release into plant cells.

PMID- 11952126
TI  - Azoarcus grass endophytes contribute fixed nitrogen to the plant in an
      unculturable state.
AB  - The extent to which the N2-fixing bacterial endophyte Azoarcus sp. strain BH72 in
      the rhizosphere of Kallar grass can provide fixed nitrogen to the plant was
      assessed by evaluating inoculated plants grown in the greenhouse and uninoculated
      plants taken from the natural environment. The inoculum consisted of either wild
      type bacteria or nifK- mutant strain BHNKD4. In N2-deficient conditions, plants
      inoculated with strain BH72 (N2-fixing test plants) grew better and accumulated
      more nitrogen with a lower delta15N signature after 8 months than did plants
      inoculated with the mutant strain (non-N2-fixing control plants). Polyadenylated
      or polymerase chain reaction-amplified BH72 nifH transcripts were retrieved from
      test but not from control plants. BH72 nifH transcripts were abundant. The
      inocula could not be reisolated. These results indicate that Azoarcus sp. BH72
      can contribute combined N2 to the plant in an unculturable state. Abundant BH72
      nifH transcripts were detected also in uninoculated plants taken from the natural
      environment, from which Azoarcus sp. BH72 also could not be isolated.
      Quantification of nitrogenase gene transcription indicated a high potential of
      strain BH72 for biological N2 fixation in association with roots. Phylogenetic
      analysis of nitrogenase sequences predicted that uncultured grass endophytes
      including Azoarcus spp. are ecologically dominant and play an important role in
      N2-fixation in natural grass ecosystems.

PMID- 11952127
TI  - A tobacco S-like RNase inhibits hyphal elongation of plant pathogens.
AB  - Ribonuclease (RNase) NE gene expression is induced in tobacco leaves in response
      to Phytophthora parasitica. Using antibodies directed against RNase NE, we
      demonstrate that RNase NE is extracellular at the early steps of the interaction,
      while the fungal tip growth is initiated in the apoplastic compartment. After
      production in Pichia pastoris and biochemical purification, we show that the S
      like RNase NE inhibits hyphal growth from P. parasitica zoospores and from
      Fusarium oxysporum conidia in vitro. Conversion into an enzymatically inactive
      form after mutagenesis of the active site-histidine 97 residue to phenylalanine
      leads to the suppression of this activity, suggesting that RNase NE inhibits the
      elongation of germ tubes by degradation of microbial RNAs. Exogenous application
      of RNase NE in the extracellular space of leaves inhibits the development of P.
      parasitica. Based on its induction by inoculation, its localization, and its
      activity against two plant pathogens, we propose that RNase NE participates in
      tobacco defense mechanisms by a direct action on hyphal development in the
      extracellular space. The RNase activity-dependent antimicrobial activity of the S
      like RNase NE shares similarities with the only other biological activity
      demonstrated for plant RNases, the inhibition of elongation of pollen tubes by
      the S-RNase in gametophytic self-incompatibility, suggesting a functional link
      between self and nonself interactions in plants.

PMID- 11952128
TI  - Dm3 is one member of a large constitutively expressed family of nucleotide
      binding site-leucine-rich repeat encoding genes.
AB  - The major cluster of resistance genes in lettuce cv. Diana contains approximately
      32 nucleotide binding site-leucine-rich repeat encoding genes. Previous molecular
      dissection of this complex region had identified a large gene, RGC2B, as a
      candidate for encoding the downy mildew resistance gene, Dm3. This article
      describes genetic and transgenic complementation data that demonstrated RGC2B is
      necessary and sufficient to confer resistance with Dm3 specificity.
      Ethylmethanesulphonate was used to induce mutations to downy mildew
      susceptibility in cv. Diana (Dm1, Dm3, Dm7, and Dm8). Nineteen families were
      identified with a complete loss of resistance in one of the four resistance
      specificities. Sequencing revealed a variety of point mutations in RGC2B in the
      six dm3 mutants. Losses of resistance were due to single changes in amino acid
      sequence or a change in an intron splice site. These mutations did not cluster in
      any particular region of RGC2B. A full-length genomic copy of RGC2B was isolated
      from a lambdaphage library and introduced into two genotypes of lettuce.
      Transgenics expressing RGC2B exhibited resistance to all isolates expressing Avr3
      from a wide range of geographical origins. In a wildtype Dm3-expressing genotype,
      many of the RGC2 family members are expressed at low levels throughout the plant.

PMID- 11952129
TI  - Transformation and transposon mutagenesis of Leifsonia xyli subsp. xyli, causal
      organism of ratoon stunting disease of sugarcane.
AB  - Conditions have been developed for genetic transformation and insertional
      mutagenesis in Leifsonia xyli subsp. xyli (Lxx), the causal organism of ratoon
      stunting disease (RSD), one of the most damaging and intractable diseases of
      sugarcane internationally. Transformation frequencies ranged from 1 to 10 colony
      forming units (CFU)/microg of plasmid DNA using Clavibacter/Escherichia coli
      shuttle vectors pCG188, pDM302, and pDM306 and ranged from 50 to 500 CFU/microg
      using cosmid cloning vectors pLAFR3 and pLAFR5-km. The
      transformation/transposition frequency was 0 to 70 CFU/microg of DNA, using
      suicide vectors pUCD623 and pSUP2021 containing transposable elements Tn4431 and
      Tn5, respectively. It was necessary to grow Lxx in media containing 0.1% glycine
      for electroporation and to amplify large plasmids in a dam-/dcm- E. coli strain
      and purify the DNA by anion exchange. To keep selection pressure at an optimum,
      the transformants were grown on nitrocellulose filters (0.2-microm pore size) on
      media containing the appropriate antibiotics. Transposon Tn4431 containing a
      promoterless lux operon from Vibrio fischeri and a tetracycline-resistance gene
      was introduced on the suicide vector pUCD623. All but 1% of the putative
      transposon mutants produce light, indicating transposition into functional Lxx
      genes. Southern blot analysis of these transformants indicates predominantly
      single transposon insertions at unique sites. The cosmid cloning vector pLAFR5-km
      was stably maintained in Lxx. The development of a transformation and transposon
      mutagenesis system opens the way for molecular analysis of pathogenicity
      determinants in Lxx.

PMID- 11952130
TI  - Tombusvirus P19-mediated suppression of virus-induced gene silencing is
      controlled by genetic and dosage features that influence pathogenicity.
AB  - The p19 protein (P19) of Tomato bushy stunt virus (TBSV) is a pathogenicity
      determinant with host-dependent effects on virus spread and symptom induction. In
      addition, results in this study confirm that Potato virus X-mediated delivery of
      P19 suppresses posttranscriptional gene silencing (PTGS). To study the relevance
      of this activity for TBSV biology, we evaluated whether TBSV activates virus
      induced gene silencing (VIGS) and if this process is suppressed by P19. TBSV
      vectors with the green fluorescent protein (GFP) gene, either active or inactive
      for P19 expression, were inoculated onto GFP-transgenic Nicotiana benthamiana
      plants. In the absence of P19 expression, VIGS was activated, as evidenced by the
      disappearance of GFP mRNA and green fluorescence. Coexpression of GFP and P19
      from the TBSV vector suppressed VIGS, except in the newly emerging leaves. The
      suppressor activity required a central P19 region that is also known to be
      essential for host-dependent virus spread and symptom induction. Defective
      interfering RNAs (DIs) that contained the 3' end of the GFP gene induced
      silencing very effectively. The concomitant DI-instigated reduction in P19
      accumulation failed to suppress this process, analogous to the known P19 dosage
      effects for other biological activities. In conclusion, (i) TBSV and its DIs are
      very effective inducers of VIGS, (ii) P19 is a strong suppressor of PTGS, (iii)
      P19 is a moderate suppressor of VIGS, and (iv) the suppressor activity is
      influenced by genetic and dosage features that are also important for P19
      associated pathogenesis.

PMID- 11952131
TI  - Functional analyses of the Pto resistance gene family in tomato and the
      identification of a minor resistance determinant in a susceptible haplotype.
AB  - Pto is a member of a multigene family and encodes a serine/threonine kinase that
      mediates gene-for-gene resistance to strains of Pseudomonas syringae pv. tomato
      expressing avrPto. The inferred amino acid sequence of the Pto homologs from both
      resistant (LpimPth2 to LpimPth4) and susceptible (LescFen, LescPth2 to LescPth5)
      haplotypes suggested that most could encode functional serine/threonine kinases.
      In addition, the activation segments of the homologs are similar in sequence to
      that of Pto, and some have residues previously identified as required for binding
      of AvrPto by Pto in the yeast two-hybrid system. The Pto homologs were therefore
      characterized for transcription, for the ability of their products to interact
      with AvrPto in the yeast two-hybrid system, for their autophosphorylation
      activity, and for their potential to elicit cell death in the presence of and
      absence of a ligand, as well as their dependence on Prf. LpimPth5, LpimPth4, and
      LescPth4 were not transcribed at levels detectable by reverse transcription
      polymerase chain reaction. The interaction with AvrPto was unique to Pto in the
      yeast two-hybrid system. LescPth2 autophosphorylated in vitro as a fusion
      protein. LpimPth2, LpimPth3, LpimPth4, LescPth3, and LescPth4 did not
      autophosphorylate in vitro. Transient expression of wild-type Fen and wild-type
      LpimPth3, as well as LescFen, LescPth3, and LescPth5 with perturbations in their
      P+1 loop caused cell death in Nicotiana benthamiana. LpimPth3 and LescPth3 with
      amino acid substitutions in the P+1 loop also elicited cell death in tomato; this
      was dependent on the presence of wild-type Prf. Consequently, some homologs could
      potentially encode functional resistance proteins. LescPth5 induced cell death
      specifically in response to expression of AvrPto in tobacco in a Prf-dependent
      manner; this is consistent with a homolog from a 'susceptible' haplotype encoding
      a minor recognition determinant.

PMID- 11952132
TI  - Molecular determinants required for the avirulence function of AvrPphB in bean
      and other plants.
AB  - The avirulence gene avrPphB from Pseudomonas syringae pv. phaseolicola determines
      incompatibility, manifested as a hypersensitive reaction (HR), on bean cultivars
      carrying the R3 resistance gene and also confers avirulence on other plants. The
      AvrPphB protein carries an embedded consensus myristoylation motif and is cleaved
      in bacteria and certain plants to yield fragments of about 6 and 28 kDa. We
      investigated plant recognition and type III translocation determinants in AvrPphB
      by constructing three N-terminally truncated and two site-directed mutants
      carrying substitutions in the conserved G63 residue of the myristoylation motif,
      which lies adjacent to the proteolytic cleavage site. The peptides were either
      delivered to plant cells by pseudomonads or were expressed transiently in planta
      via the Agrobacterium tumefaciens or Potato virus X. The 63 amino terminal
      residues were required for type III-mediated translocation from Pseudomonas
      strains to the plant, but were partially dispensable for effector recognition
      following in planta expression. Substitution of the G63 residue resulted in
      differential HR phenotypes in two different R3 cultivars of bean and abolished
      effector processing in Pseudomonas strains. Agrobacterium-mediated expression of
      the mutant proteins elicited HR in resistant bean hosts and in tomato but
      elicited no reaction in Nicotiana species.

PMID- 11952133
TI  - Type I interferons (IFN) are essential mediators of innate and specific immunity
      against viruses.

PMID- 11952134
TI  - CD8+ T-cell response against hepatitis C virus.
AB  - CD8+ T-cell response is thought to be important for the control of hepatitis C
      virus (HCV) as well as for the liver cell injury caused by HCV infection. Studies
      on antigen-specific CD8+ T cells had long been hampered by lack of suitable
      techniques. Recently developed single-cell based assays, including peptide major
      histocompatibility complex (MHC) tetramer staining and intracellular cytokine
      staining, have greatly enhanced the opportunities for directly studying HCV
      specific CD8+ T cells. Thanks to these novel assays the quantitative and
      qualitative nature of HCV-specific CD8+ T cells, including their number,
      phenotype, and effector functions, are starting to be revealed. However, much
      important information remains missing, including the signals for differentiation
      and migration of HCV-specific CD8+ T cells and the precise functions of antigen
      specific effector cells in the virus-infected liver. The urgent need for
      effective immunotherapy and vaccines can not be met without a better
      understanding of the CD8+ T-cell response in HCV infection, which calls for a
      comprehensive strategy to study such cells directly using sensitive and
      quantitative assays.

PMID- 11952135
TI  - Distinct roles of eicosanoids in the immune response to viral encephalitis: or
      why you should take NSAIDS.
AB  - Prostaglandins (PGs) and leukotrienes (LTs) are important proinflammatory
      mediators. They are both derived from arachidonic acid (AA). Cyclooxygenase
      (COX), the key enzyme in transforming AA into PGs, has two isoforms: COX-1 is
      constitutively expressed, and COX-2, is inducible. Lipoxygenase (5-LO) is the key
      enzyme for LT production. PGs and LTs have been intensively studied. Release of
      these molecules is associated with mucus secretion, redness, pain, fever and
      other inflammatory manifestations. Both PGs and LTs are involved in host defense
      against various pathogens. In addition to mediating inflammatory symptoms, PGs
      might suppress some innate immune factors, including nitric oxide (NO)
      production. PGs also suppress a TH1 response. LTs have pathologic potential,
      especially in asthma. LTs also have been found to have positive roles in host
      defense, either against virus or bacteria. Finally, PGs and LTs might regulate
      the production of each other, possibly at the level of substrate competition by
      their enzymes. Because they are clinically important molecules, a further
      understanding of the roles that PGs and LTs played in host defense will have
      great impact on therapeutic research.

PMID- 11952136
TI  - Human fibroblasts transfected with cytomegalovirus immediate-early genes show
      increased MHC class I expression and are targets for natural killer cell-mediated
      cytotoxicity.
AB  - Natural killer (NK) cells are an important line of defense against viral
      infections, such as those caused by cytomegalovirus (CMV), but in the context of
      solid organ transplantation NK responses to CMV-infected graft cells might be
      deleterious to the graft survival. To gain a better understanding of NK responses
      to CMV-infected human lung fibroblasts (HLF), we transfected HLF with a plasmid
      expressing CMV immediate-early (IE) genes under the control of the CMV major IE
      promoter and compared major histocompatibility complex (MHC) class I expression
      and NK-mediated lysis of transfected cells, CMV-infected cells, and appropriate
      controls. HLF transfected with CMV IE genes showed increased MHC Class I
      expression and triggered NK-mediated cytotoxicity at the same level as CMV
      infected HLF and at significantly higher levels than mock-infected or mock
      transfected controls. Transfection of CMV genes provides an experimental model
      for molecular studies of CMV- and allograft-specific cell-mediated immunity and
      modulation.

PMID- 11952137
TI  - Encephalomyocarditis and Mengo viruses productively infect murine T-lymphocyte
      cell lines but not fresh ex vivo derived T lymphocytes.
AB  - Encephalomyocarditis virus (EMCV) and Mengo virus are highly virulent murine
      cardioviruses that are found in abundant quantities in the spleen and lymph nodes
      after infection. T lymphocytes are pivotal mediators of humoral and cellular
      immunity against cardioviral challenge, and are highly suspect candidates of EMCV
      and Mengo virus infection. We found T lymphocyte-like cell lines CTLL-2, EL-4,
      LY1+2/9, and LBRM33 were susceptible to productive viral infection and exhibited
      cytopathology after infection with virulent EMCV-R or attenuated Mengo virus
      strains vMC0 and vMC24. Flow cytometric analysis demonstrated progressive
      intracellular accumulation of viral proteins, such as the replication-dependent
      3D viral polymerase, in EL-4 cells during infection. Conversely, freshly isolated
      and mitogen-stimulated CD4+ and CD8+ T cells were resistant to productive
      infection with these viruses, exhibiting no viral-induced cytopathic effects or
      intracellular presence of viral proteins. These data indicate that although T
      lymphocyte-like tumor cell lines are highly susceptible to viral infection and
      cytopathic effects, primary/freshly isolated T cells are resistant to infection
      by EMCV-R or Mengo virus.

PMID- 11952138
TI  - Immunization with influenza virus hemagglutinin globular region containing the
      receptor-binding pocket.
AB  - The globular region of hemagglutinin (residues 91-261) membrane glycoprotein of
      influenza virus that encompasses the binding zone to the oligosaccharide receptor
      of target cells has been cloned by reverse transcriptase-polymerase chain
      reaction (RT-PCR). This protein segment (denoted HA91-261 peptide) induced
      significant immune response in mice. The serum antibodies and lung homogenates
      from the immunized mice cross-reacted with native virus particles. The cellular
      immunity was manifested by proliferative splenocyte responses and cytokine
      release indicating T helper type 1 activity. The plasmid DNA containing this
      segment (denoted pHA91-261) provoked, in addition, a significant cytotoxic T
      lymphocyte (CTL) response, whereas the HA91-261 protein fragment led to no such
      response. Both the DNA and the protein fragment of HA91-261 induced significant
      protection against viral challenge, although the immune response they induce
      might be along different pathways. Interestingly, the combined DNA priming
      protein boosting immunization regimen did not induce protection against viral
      challenges even though it led to significant humoral immune responses similar to
      that induced by the peptide vaccine.

PMID- 11952139
TI  - The role of interferon regulatory factors in the cardiac response to viral
      infection.
AB  - Reovirus-induced murine myocarditis provides an excellent model for the human
      disease. Cardiac tissue damage varies between reovirus strains, and is caused by
      a direct viral cytopathogenic effect. One determinant of virus-induced cardiac
      tissue damage is the cardiac interferon-beta (IFN-beta) response to viral
      infection. Nonmyocarditic reoviruses induce more IFN-beta and/or are more
      sensitive to the antiviral effects of IFN-beta in cardiac cells than myocarditis
      reoviruses. The roles of interferon regulatory factors (IRFs) in the cardiac
      response to viral infection are reviewed, and results suggest possible cardiac
      specific variations in IRF-3 and IRF-1 function. In addition, data are presented
      indicating that the role of IRF-2 in regulation of IFN-beta expression is cell
      type-specific and differs between skeletal and cardiac muscle cells. Together,
      results suggest that the heart may provide a unique environment for IRF function,
      critical for protection against virus-induced cardiac damage.

PMID- 11952140
TI  - Mapping of B-cell epitopes in the nucleocapsid protein of Puumala hantavirus.
AB  - Hantavirus nucleocapsid protein (N) has been proven to induce highly protective
      immune responses in animal models. The knowledge on the mechanisms behind N
      induced protection is still limited, although recent data suggest that both
      cellular and humoral immune responses are of importance. For a detailed B-cell
      epitope mapping of Puumala hantavirus (PUUV) N, we used recombinant N derivatives
      of the Russian strain CG18-20 and the Swedish strain Vranica/Hallnas, as well as
      overlapping synthetic peptides corresponding to the Finnish prototype strain
      Sotkamo. The majority of a panel of monoclonal antibodies (mAbs) reacted with
      proteins derived from all included PUUV strains demonstrating the antigenic
      similarity of these proteins. In line with previous results, the epitopes of most
      mAbs were mapped within the 80 N-terminal amino acids of N. The present study
      further revealed that the epitopes of four mAbs raised against native viral N
      were located within amino acids 14-45, whereas one mAb raised against recombinant
      N was mapped to amino acids 14-39. Differences between the reactivity of the PUUV
      strains Vranica/Hallnas and CG18-20 N suggested the importance of amino acid
      position 35 for the integrity of the epitopes. In line with the patterns obtained
      by the truncated recombinant proteins, mapping by overlapping peptides (PEPSCAN)
      confirmed a complex recognition pattern for most analyzed mAbs. Together, the
      results revealed the existence of several, partially overlapping, and
      discontinuous B-cell epitopes. In addition, based on differences within the same
      competition group, novel epitopes were defined.

PMID- 11952141
TI  - Differential processing of HLA A2-restricted HIV type 1 cytotoxic T lymphocyte
      epitopes.
AB  - Cytotoxic T lymphocytes (CTLs) play a key role in the control of persistent viral
      infections. Differences in the quality of this cellular immune response influence
      the long-term outcome of such infections, but the factors that determine which
      virus-derived peptide epitopes are targeted by CTLs remain poorly understood.
      Here, we examine the antigen-processing requirements of three human leukocyte
      antigen (HLA) A*0201-restricted HIV-1 CTL epitopes. Each of these three peptides
      appears to be generated by a distinct proteolytic pathway, despite presentation
      on the cell surface in association with the same HLA class I molecule.
      Presentation of the commonly immunodominant SLYNTVATL (HIV-1 p17 Gag; residues 77
      85) epitope was unaffected by inhibition of the proteasome with lactacystin, but
      was dependent on the presence of the beta-subunit LMP7. These findings are
      consistent with emerging data on the complexity of peptide epitope generation,
      and suggest that differences in antigen processing might contribute to patterns
      of CTL recognition in vivo.

PMID- 11952142
TI  - Enhancement of natural killer cell activation and antibody-dependent cellular
      cytotoxicity by interferon-alpha and interleukin-12 in vaginal mucosae Sivmac251
      infected Macaca fascicularis.
AB  - We studied the innate immune system of Cynomolgus monkeys (Macaca fascicularis)
      experimentally infected via the vaginal mucosae with a virulent simian
      immunodeficiency virus isolate SIVmac251. Animals were evaluated for their
      natural killer (NK) cell activity, and for their antibody-dependent cellular
      cytotoxicity. NK cells from SIVmac251-infected macaques show impaired NK cell
      activity compared to cells from uninfected animals. Subsequent treatment of NK
      cells with interferon-a (IFN-alpha) or interleukin-12 (IL-12) alone partially
      restored the NK activity. However, either treatment of NK cells with both IFN
      alpha and IL-12 completely reversed the impairment of cytotoxicity induced by
      simian immunodeficiency virus (SIV) infection. Incubation of NK cells from
      infected but not from uninfected monkeys with IFN-alpha and IL-12 for 8 days
      increased the percentage of CD16+/CD56+ cells twofold to five-fold and enhanced
      antibody-dependent cellular cytotoxicity (ADCC) activity. Thus IFN-alpha and IL
      12 greatly enhance both the NK cell and ADCC activities of peripheral blood cells
      from SIVmac251-infected animals and increase the number of NK cells in longer
      term culture. The combined effect of IFN-alpha and IL-12 in enhancing NK cell
      activity may provide a novel therapeutic approach for the restoration of
      depressed NK cell activity observed in human immunodeficiency virus (HIV)
      infected patients.

PMID- 11952143
TI  - Interferon--gamma control of EBV-transformed B cells: a role for CD8+ T cells
      that poorly kill EBV-infected cells.
AB  - Control of Epstein-Barr virus (EBV) infection requires CD8+ T cells.
      Surprisingly, many EBV-specific CD8+ T cells kill autologous EBV-transformed B
      lymphoblasts poorly. We investigated the effector functions used by poorly
      cytotoxic EBV-specific CD8+ D7 cloned T cells and by EBV-stimulated peripheral
      blood lymphocytes. D7 T cells did not inhibit B lymphoblast growth in long-term
      coculture, but prevented the outgrowth of newly infected autologous B cells.
      Optimally stimulated D7 T cells and EBV-stimulated peripheral blood lymphocytes
      produced interferon (IFN)-y at levels that inhibited EBV-transformed B cell
      outgrowth. Inhibitory factor activity was neutralized by anti-IFN-gamma
      monoclonal antibodies (mAb), but not by antibodies to several other cytokines.
      These data suggest an in vivo role for IFN-y secreting EBV-specific CD8+ T cells.

PMID- 11952144
TI  - Activation of the interferon-beta promoter during hepatitis C virus RNA
      replication.
AB  - In this study we examined the impact of hepatitis C virus (HCV) RNA replication
      on the innate antiviral response of the host cell. Replication of an HCV
      subgenomic replicon stimulated the activation of the interferon (IFN)-beta
      promoter and the production of IFN in human hepatoma cells. Using a variety of
      functional assays, we found that HCV RNA replication induced the activation and
      DNA-binding activity of NFkappaB and interferon regulatory factor (IRF)-1. In
      addition, microscopy experiments revealed a higher frequency of cells containing
      the nuclear-localized, active form of IRF-3 in HCV replicon cultures versus
      control cultures. Consistent with these observations, cells harboring the HCV
      replicon exhibited high basal level expression of a subset of IFN-stimulated
      antiviral genes. Our results indicate that HCV RNA replication can stimulate
      cellular antiviral programs that contribute to the assembly and activation of the
      IFN-beta enhanceosome complex and initiation of the antiviral state. Stable HCV
      RNA replication in the face of the host antiviral response suggests that HCV may
      encode one or more proteins capable of overcoming specific antiviral processes,
      thereby supporting persistent infection.

PMID- 11952145
TI  - Activation and inhibition of virus and interferon: the herpesvirus story.
AB  - Viral infection of a host leads to induction of an immune system attack against
      the virus along with a counterattack by the virus against the host. Interferons
      are highly upregulated upon viral infection and function as key regulators of the
      host innate defense system. Whereas many RNA viruses are sensitive to the effects
      of interferon, several of the large DNA viruses are relatively resistant, given
      their capacity to encode proteins that disarms the host response. The herpesvirus
      family is a large and diverse family of viruses that infects vertebrates and
      invertebrates and possesses the ability to remain latent in their host for life.
      This paper summarizes the relationship between herpesviruses and interferon,
      including the ability of herpesviruses to induce interferon production,
      mechanisms by which interferon decreases herpesvirus replication, and strategies
      of herpesviruses to counteract these mechanisms.

PMID- 11952146
TI  - PKR protection against intranasal vesicular stomatitis virus infection is mouse
      strain dependent.
AB  - The interferon-induced antiviral state is mediated by interferon-stimulated genes
      that are upregulated in concert after stimulation by type I interferons. Because
      so many viruses encode strategies to inactivate the interferon-inducible double
      stranded RNA (dsRNA)-dependent protein kinase PKR, this protein is likely to be a
      major player in antiviral defense. Here we demonstrate the increased
      susceptibility of PKR-/- animals to vesicular stomatitis virus (VSV) by the
      intranasal route, but also demonstrate that the protective effects of PKR are
      mouse strain dependent. We have found the difference between wild-type-BALB/c and
      129SvEv animals to be on the order of 5 logs, with high levels of virus present
      in the lungs of BALB/c but not 129SvEv animals. To evaluate the sensitivity of
      PKR-/- mice to VSV clearly, the PKR mutation was bred onto the resistant 129SvEv
      background. The increased sensitivity of PKR-/- mice, compared to PKR+/+ strain
      matched controls, is on the order of 10-fold as measured by median lethal dose
      (LD50). PKR-/- 129 mice support VSV replication in the lung unlike controls.
      While this result clearly demonstrates an important role for PKR in protection
      against VSV infection of the lung, it also underlines the importance of other
      host factors in containing a viral infection.

PMID- 11952148
TI  - Skin allograft rejection is suppressed in mice lacking the antiviral enzyme,
      2',5'-oligoadenylate-dependent RNase L.
AB  - The 2-5A/RNase L system is a regulated RNA decay pathway that mediates some of
      the antiviral and tumor suppressor activities of the interferons. Previously, we
      demonstrated that RNase L-null mice have increased susceptibility to viral
      infections and are partially deficient in induced and spontaneous apoptosis. To
      determine if RNase L functions in cellular, as well as innate, immunity, skin
      allograft rejection and contact hypersensitivity (CHS) experiments were performed
      in RNase L+/+ and RNase L-/- mice. Although no consistent alterations in CHS were
      found, we did observe a delay of 5 days in the acute rejection of class II major
      histocompatibility complex (MHC) disparate skin allografts in mice lacking RNase
      L. Accordingly, histologic examinations of the allografts harvested from RNase L
      /- mice revealed a dramatic reduction in inflammatory infiltrates, suggesting a
      delay in T-cell priming or a deficiency in immune cell trafficking. Results
      consistent with a proinflammatory role for RNase L extend the known functions of
      the 2-5A/RNase L system beyond innate immunity into some, but not all, types of
      cellular immunity.

PMID- 11952147
TI  - Effects of PKR/RNase L-dependent and alternative antiviral pathways on alphavirus
      replication and pathogenesis.
AB  - Type I interferons (IFN-alpha/beta) rapidly confer resistance to alphavirus
      infection in macrophages and dendritic cells (DC) as evidenced by the
      dramatically increased susceptibility of these cells in mice with the IFNAR1
      subunit of the IFN-alpha/beta receptor ablated (IFNAR1-/-). Normal adult mice
      develop only a subclinical Sindbis virus infection, whereas infected IFNAR1-/-
      mice rapidly succumb to a fatal disease. Here, we investigated the individual and
      combined contributions of the two best characterized INF-alpha/beta-mediated
      antiviral pathways to the control of Sindbis virus replication: (1) the coupled 2
      5A synthetase/RNase L pathway and (2) the double-stranded RNA-dependent protein
      kinase (PKR) pathway. Surprisingly, mice deficient in PKR, RNase L, and Mx-1
      (triply-deficient [TD]) developed only subclinical infection. Although the
      permissivity of cells in lymph nodes draining the inoculation site was increased
      in the absence of PKR/RNase L, systemic dissemination of the virus infection was
      restricted by an alternative IFN-alpha/beta receptor-dependent mechanism. In
      vitro, suppression of early virus protein synthesis and virion production in
      primary bone marrow-derived dendritic cells (BMDC) was largely dependent on the
      PKR pathway. However, later in infection virion production was reduced even in
      the absence of PKR/RNase L by an IFN-alpha/beta receptor-dependent mechanism.
      Priming of BMDC with IFN-alpha/beta or IFN-gamma resulted in dose-dependent
      restriction of virus replication, largely independent of PKR and/or RNase L
      expression.

PMID- 11952149
TI  - Interferon type I downregulates human parainfluenza virus type 3-induced major
      histocompatibility complex class II expression.
AB  - Human parainfluenza virus type 3 (HPIV3) induces major histocompatibility complex
      (MHC) class II expression in a signal transducer and activator of transcription-1
      (STAT1)- and class II transactivator (CIITA)-independent manner. Interferon (IFN)
      gamma, the potent inducer of MHC class II, on the other hand, requires both STAT1
      and CIITA in the induction process. IFN-alpha/beta has been shown to inhibit the
      IFN-y-induced expression of MHC class II by targeting a step(s) downstream of
      CIITA. Here we report that IFN-alpha/beta also inhibits the CIITA-independent
      expression of HPIV3-induced MHC class II. The inhibitory role of IFN-alpha/beta
      on HPIV3-induced MHC class II was confirmed by using anti-IFN-alpha/beta antibody
      and mutant cell lines defective in the IFN signaling components STAT1 and STAT2.
      IFN-alpha/beta inhibits virus-induced MHC class II expression just as it does IFN
      gamma-induced MHC class II. The inhibition by IFN-alpha/beta of MHC class II
      expression may play a regulatory role in virus induced autoimmune disease
      mediated by MHC class II aberrant expression.

PMID- 11952150
TI  - To interfere and to anti-interfere: the interplay between hepatitis C virus and
      interferon.
AB  - As popular strategies used by numerous viruses, interception of interferon (IFN)
      signaling and inhibition of IFN-induced antiviral functions allow viruses to
      evade the host immune response and set up successful infections. Hepatitis C
      virus (HCV), the leading cause of chronic liver disease worldwide and a major
      public health hazard, causes persistent infection in the majority of infected
      individuals. IFN-based therapies, currently the only ones available for HCV
      infection, have been unable to eliminate viral infection in the majority of
      patients, and many studies suggest that HCV possesses mechanisms to antagonize
      the IFN-induced antiviral response. Multiple viral, host, and IFN-associated
      factors have been implicated in the interplay between HCV and IFN. Two viral
      proteins, NS5A and E2, became the focus of much attention and extensive study
      because of their abilities to inhibit IFN-induced, double-stranded RNA-activated
      protein kinase (PKR), a major mediator of the IFN-induced biologic response, and
      to perturb the IFN signaling pathway. In this review, we discuss the significance
      of the interferon sensitivity determining region (ISDR) within NS5A, which has
      been the subject of intense debates. In addition, we discuss the potential
      mechanisms by which NS5A interferes with IFN signaling and the current working
      models. Further understanding of the molecular mechanisms underlying the
      interaction between HCV and IFN will likely facilitate improvement of current IFN
      based therapies and development of novel treatments for the HCV pandemic. Future
      HCV research will benefit from both the development of efficient, convenient
      model systems for viral propagation, and the utilization of high throughput,
      genomic-scale approaches.

PMID- 11952151
TI  - Proteolytic signals in the primary structure of annexins.
AB  - Annexins are a superfamily of calcium-dependent membrane-associated proteins
      which interact with phospholipids. The primary structure of Annexins I, III, VII,
      VIII and XI contain a region enriched in proline, glutamate, serine and threonine
      (PEST sequences) towards the N-terminal end while annexins II, V and VI possess
      PEST regions somewhat distal to the N-terminus. These PEST sequences are believed
      to be the signals for rapid intracellular degradation. Annexin I is known to be
      cleaved by calpain near its PEST region suggesting that its PEST region might be
      a possible calpain recognition site. Western blot analysis of annexins V and XI
      in rat lung homogenates suggest that these proteins are resistant to proteolysis
      by calpain. Annexin V was found to be stable to intrinsic lung proteases in the
      presence of either Ca2+ or EGTA while annexin XI was found to be partially
      degraded by intrinsic lung proteases in the presence of EGTA. Eight of the 10
      known mammalian annexins also contain a pentapeptide sequence that is
      biochemically related to the KFERQ motif which is a known signal that targets
      protein for lysosomal proteolysis. Our data suggest that the annexins may be
      regulated by limited proteolysis, most likely at their N-terminal end, while
      most, if not all, of them might be degraded by the lysosomal pathway.

PMID- 11952152
TI  - Modulation of cardiac A1-adenosine receptors in rats following treatment with
      agents affecting heart rate.
AB  - Effects of chronic treatment affecting heart rate on A1 adenosine receptor levels
      and their functions were studied. Treatment of rats with isoproterenol for 10
      days accelerated heart rate and increased the level of adenosine receptors, in
      both the atria and ventricles. Negative dromotropic response of isolated heart to
      adenosine was enhanced in isoproterenol-treated rats. Similar results were
      obtained following treatment with atropine sulfate, or swimming training but not
      after treatment with thyroxine. On the other hand, treatment with amiodarone,
      which normally causes a decrease in heart rate, also increased the level of
      adenosine receptors in both atria and ventricles. The sensitivity of the isolated
      heart to the negative dromotropic and chronotropic effects of adenosine was not
      enhanced in the amiodarone treated rats. Similar results were obtained following
      treatment with propranolol, while treatment with PTU (6-n-propyl-2-thiouracil)
      increased adenosine sensitivity in the isolated heart. It was concluded that the
      levels of A1 adenosine receptors in the heart correspond to heart rate, and to
      cardiac efficiency. While an increase in heart rate was followed by up-regulation
      of A1 adenosine receptors, a decrease in heart rate caused a moderate elevation
      of these receptors.

PMID- 11952153
TI  - Purification and characterization of cytosolic glycerol-3-phosphate dehydrogenase
      from skeletal muscle of jerboa (Jaculus orientalis).
AB  - Cytosolic glycerol-3-phosphate dehydrogenase was purified from jerboa (Jaculus
      orientalis) skeletal muscle and its physical and kinetic properties investigated.
      The purification method consisted of a multi-step procedure and this procedure is
      presented. The specific activity of the purified enzyme is 53.6 U/mg of protein,
      representing a 77-fold increase in specific activity. The apparent Michaelis
      constant (Km) for dihydroxyacetone is 137.39 (+/- 25.56) microM whereas the Km
      for glycerol-3-phosphate is 468.66 (+/- 27.59) microM. The kinetic mechanism of
      purified enzyme is 'ordered Bi-Bi' and this result is confirmed by the product
      inhibition pattern. Under the conditions of assay, the pH optimum occurs at pH
      7.7 for the reduction of dihydroxyacetone phosphate and at pH 9.0 for glycerol-3
      phosphate oxidation. In the direction of dihydroxyacetone phosphate, the optimal
      temperature is 35 degrees C. The molecular weight of the purified enzyme
      determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis is 33,000
      (+/- 1000), whereas non-denaturing polyacrylamide gel yields a molecular weight
      of 72,000 (+/- 2000), suggesting that the enzyme may exist as a dimer. A
      polyclonal antiserum raised against the purified enzyme was used to localize the
      enzyme in different jerboa tissues by Western blot method. The purified enzyme is
      sensitive to N-ethylmaleimide, and incubation of the enzyme with 20 mM N
      ethylmaleimide resulted in a complete loss of catalytic activity. The purified
      enzyme is inhibited by several metal ions including Zn2+ and by 2,4
      dichlorophenoxyacetic acid.

PMID- 11952155
TI  - Differential modulation of transforming growth factor-betas and cyclooxygenases
      in the platelet lysates of male F344 rats by dietary lipids and piroxicam.
AB  - Platelets are implicated in the pathogenesis of various chronic diseases
      including cancer. The main objective of the present study was to determine if
      dietary fish oil and piroxicam, known modulators of colon tumorigenesis, effect
      transforming growth factor (TGF)-betas and cyclooxygenase (COX) isozymes in the
      platelets of colon tumor-bearing male F344 rats. TGF-betas and COXs are important
      in the development of chronic illnesses including colon cancer. Animals harboring
      preneoplastic colonic lesions were randomly allocated to a low fat diet (5% by
      weight--low corn oil, LFC) and three high fat diets (23% by weight--high corn
      oil, HFC; high corn oil containing 150-ppm piroxicam, HFC+P; and high fish oil,
      HFF) for 16 weeks. TGF-beta1, TGF-beta2, COX-1 and COX-2 protein levels were
      assessed in the platelets by Western blot analysis. Active TGF-beta1 (12.5 kDa)
      level was significantly lower in the platelets of the HFC+P group (p < 0.001),
      whereas precursor TGF-beta1 (39 kDa) level was significantly lower in the
      platelets of the HFF group (p < 0.001). The anti-rabbit TGF-beta2 polyclonal
      antibody did not detect the 13-kDa active TGF-beta2 protein in the platelets.
      However a 29-kDa protein, potentially a precursor of TGF-beta2, was detected in
      the platelets of all the groups and was significantly lower in the HFC+P and HFF
      groups than in LFC and HFC (p < 0.001). COX-1 level was significantly lower in
      the HFF group than the other three groups (p < 0.001). COX-2 protein was detected
      in the platelets of all diet groups. Piroxicam in the presence of high corn oil
      (HFC+P) significantly lowered the level of COX-2 (p < 0.001), without having any
      effect on COX-1 level. These findings conclusively show that LFC and HFC differ
      from HFF and HFC+P, and piroxicam differs from fish oil, in regulating the levels
      of TGF-betas and COX in the platelets. This supports the conjecture that the
      levels of bioactive constituents of the platelets are profoundly modulated by
      dietary lipids, which in turn could influence the pathogenesis of chronic
      illnesses.

PMID- 11952154
TI  - Exercise conditioning attenuates the hypertensive effects of nitric oxide
      synthase inhibitor in rat.
AB  - Many individuals with cardiovascular diseases undergo periodic exercise
      conditioning with or with out medication. Therefore, this study investigated the
      interaction of exercise training and chronic nitric oxide synthase (NOS)
      inhibitor (Nitro-L-Arginine Methyl Ester, L-NAME) treatment on blood pressure and
      its correlation with aortic nitric oxide (NO), antioxidant defense system and
      oxidative stress parameters in rats. Fisher 344 rats were divided into four
      groups: (1) sedentary control, (2) exercise training (ET) for 8 weeks, (3) L-NAME
      (10 mg/kg, subcutaneous for 8 weeks) and (4) ET + L-NAME. Blood pressure (BP) was
      monitored weekly for 8 weeks with tail-cuff method. The animals were sacrificed
      24 h after last treatments and thoracic aortic rings were isolated and analyzed.
      Exercise conditioning resulted in a significant increase in respiratory exchange
      ratio (RER), aortic NO production, NO synthase activity and inducible iNOS
      protein expression. Training significantly enhanced aortic GSH levels, GSH/GSSG
      ratio and up-regulation of aortic CuZn-SOD, Mn-SOD, catalase (CAT), glutathione
      peroxidase (GSH-Px) activity and protein expression and significantly decreased
      aortic lipid peroxidation. Chronic L-NAME administration resulted in a
      significant depletion of aortic NO, NOS activity, endothelial (eNOS) and iNOS
      protein expression, GSH level, GSH/GSSG ratio, down-regulation of aortic
      antioxidant enzyme activities and protein expressions. Aortic xanthine oxidase
      (XO) activity significantly increased with increased lipid peroxidation and
      protein oxidation after L-NAME administration. The biochemical changes were
      accompanied by increased in BP. Interaction of training and chronic NOS inhibitor
      treatment resulted in normalization of BP and aortic antioxidant enzyme activity
      and protein expression, up-regulation of aortic GSH/GSSG ratio, NO levels, Mn-SOD
      protein expression, depletion of GSSG, protein oxidation and lipid peroxidation.
      The data suggest that training attenuated the oxidative injury caused by chronic
      NOS inhibitor treatment by up-regulating the NO and antioxidant systems and
      lowering the BP in rats.

PMID- 11952157
TI  - The effect of boromycin on the Ca2+ homeostasis.
AB  - A boron-containing antibiotic, boromycin (BM), was found to influence the Ca2+
      homeostasis in both excitable and non-excitable cells. In non-excitable cells
      (human erythrocytes and leucocytes) it inhibited the resting passive 45Ca2+
      transport in 10(-6)-10(-5) mol/L concentrations. In human erythrocytes, the
      passive 15Ca2+ transport induced by the presence of 1 mmol/L NaVO3 was inhibited
      by boromycin (90% inhibition) as well. The inhibitory effect of BM on the NaVO3
      induced passive 45Ca2+ transport was diminished in the presence of inhibitory
      concentrations of nifedipine (10 micromol/L -60% inhibition) or of those of K+o
      (75 mmol/L -20% inhibition). On the other hand, in rat brain synaptosomes, and
      rat cardiomyocytes, BM stimulated the passive 45Ca2+ transport in 'resting' cells
      at similar concentrations. In rat cardiomyocytes the stimulation was transient.
      The stimulatory effect on the passive 45Ca2+ transport in rat brain synaptosomes
      was accompanied with the increase of cytoplasmic Ca2+ concentration measured by
      means of the entrapped fluorescent Ca2+ chelator fura-2. The stimulatory effect
      of BM was diminished when synaptosomes were pre-treated with veratridine (10
      micromol/L) which itself stimulated the passive 45Ca2+ transport. At saturating
      concentrations of veratridine, no stimulatory effect of BM was observed. These
      results could be explained by the indirect interaction of BM with both Ca2+ and
      Na+ transport systems via transmembrane ionic gradients of monovalent cations and
      could be useful in determining whether the cells belong to excitable, or non
      excitable cells.

PMID- 11952156
TI  - Characterization of the calcium-dependent proteolytic system in a mouse muscle
      cell line.
AB  - Many studies have demonstrated that the calcium-dependent proteolytic system
      (calpains and calpastatin) is involved in myoblast differentiation. It is also
      known that myogenic differentiation can be studied in vitro. In the present
      experiments, using a mouse muscle cell line (C2C12) we have analyzed both the
      sequences of appearance and the expression profiles of calpains 1, 2, 3 and
      calpastatin during the course of myoblast differentiation. Our results mainly
      show that the expression of ubiquitous calpains (calpain 1 and 2) and muscle
      specific calpain (calpain 3) at the mRNAs level as well as at the protein level
      do not change significantly all along this biological process. In the same time,
      the specific inhibitor of ubiquitous calpains, calpastatin, presents a stable
      expression at mRNAs level as well as protein level, all along myoblast to myotube
      transition. A comparison with other myogenic cells is presented.

PMID- 11952158
TI  - Activation of the human transforming growth factor alpha (TGF-alpha) gene by the
      hepatitis B viral X protein (HBx) through AP-2 sites.
AB  - The HBx protein is known as a transactivator and potential oncogene, and TGF
      alpha as a potent mitogen in hepatocellular carcinoma. By assays of serial
      deletion of the promoter of TGF-alpha gene and the cotransfection of HBx and AP-2
      expression vectors, we observed that the HBx significantly activated the promoter
      activity through AP-2 sites located in the proximal region of the TGF-alpha
      promoter (-136 to -30). This effect was also observed in the heterologous
      promoter assay system containing AP-2 sites. The mutation analyses of three AP-2
      sites in the promoter revealed that all three AP-2 sites contributed to the
      activation of the TGF-a gene in the presence of HBx. Accordingly, the mRNA level
      of TGF-alpha was significantly elevated in the HBx-expressing cell, HepG2-HBx and
      the HBV-producing cell, HepG2-K8. These results suggest that the HBx protein
      could increase the mitogenic effect of TGF-alpha by the transactivation of the
      gene through AP-2 binding sites and consequently, these interactions may
      accelerate the process of hepatocarcinogenesis.

PMID- 11952159
TI  - Identification of genes enhanced by protein-calorie malnutrition by differential
      display polymerase chain reaction (expression of fibrinogen B beta chain, B cell
      translocation gene 1 and thyroid hormone responsive protein genes).
AB  - Protein-calorie malnutrition (PCM), as one of global health problems, arises
      during protein and/or energy deficit due to disease and nutritional inadequacy.
      Previously, we showed that PCM elicited oxidative stress with activation of the
      phase II detoxifying gene expression, which was reversed by cysteine
      supplementation. As part of the attempts to identify the cellular adaptive
      responses and the associated gene expression during PCM, the current study was
      initiated to analyze the genes differentially expressed in the rat during PCM.
      Among 1,916 bands amplified, 85 putative differentially amplified bands were
      enhanced by PCM in the liver, while the expression of 64 bands was suppressed.
      Northern and/or reverse transcription-polymerase chain reaction (RT-PCR) analyses
      revealed that PCM increased the expression of fibrinogen B beta chain, B cell
      translocation gene I (BTGI) and thyroid hormone responsive protein (THRP) mRNAs.
      The increase in the hepatic fibrinogen B beta chain mRNA was not prevented by
      cysteine supplementation, whereas cysteine decreased the enhancement in the
      rGSTA2 and microsomal epoxide hydrolase mRNA expression. Cysteine was also active
      in reversing the increase in BTG1 mRNA during PCM. This was supported by the
      increase in BTG1 mRNA in H4IIE cells exposed to sulfur amino acid-deprived
      medium. Northern blot analysis revealed that THRP, highly expressed in the brain
      in a tissue-specific manner, was induced by PCM and that cysteine supplementation
      abolished the THRP induction. Conversely, the level of hepatic albumin mRNA was
      markedly decreased by PCM, which was partially restored by cysteine
      supplementation. Differential display RT-PCR analysis allowed us to identify the
      genes that are responsive to oxidative stress during PCM and to characterize the
      differential role of cysteine on the expression of the fibrinogen B beta chain,
      BTG1 and THRP genes as a homeostatic adaptive response during protein deficiency.

PMID- 11952160
TI  - Molecular basis of 2',3'-dideoxycytidine-induced drug resistance in human cells.
AB  - Human monoblastoid cells (U937) grown in the presence of therapeutically relevant
      dideoxycytidine concentrations (0.1 microM) become resistant to the drug thanks
      to an altered deoxycytidine kinase. In this paper we show that deoxycytidine
      kinase mRNA is significantly reduced in drug-resistant U937 cells (U937-R)
      although the deoxycytidine kinase promoter is normal. Anumber of nucleotide
      deletions, insertions and substitutions was found in the coding region of
      deoxycytidine kinase gene. Several identified mutations result in truncated forms
      of the enzyme or in the introduction of stop codons: in one case a complete lack
      of exon 4 was found. Thus, the deoxycytidine kinase gene accumulates mutations at
      a very high rate, as already reported for other cytidine analogues (i.e. Ara C)
      suggesting that the design of new antiviral or anticancer drugs of the cytidine
      family should take into account the potential development of cell resistance as a
      critical factor in drug failure.

PMID- 11952161
TI  - Influence of zinc ions on protein secretion in a heavy metal tolerant strain of
      the ericoid mycorrhizal fungus Oidiodendron maius.
AB  - A heavy metal tolerant strain of the ericoid mycorrhizal species Oidiodendron
      maius, isolated from soil heavily contaminated with zinc, was previously shown to
      tolerate high concentrations of zinc and cadmium ions in the growth medium. We
      have investigated some of the specific molecular responses of this fungal strain
      to the presence of increasing concentrations of zinc ions in the growth medium.
      In particular, we show that zinc ions induce a general change in the array of
      secreted proteins, with a shift towards the production of more basic, low
      molecular weight polypeptides. Some of these proteins were microsequenced and
      identified through homology search in databases. Among them are hydrolytic
      enzymes (nuclease, proteinase, lysozyme) and two superoxide dismutase isoforms.
      The latter are antioxidant enzymes known to play a role in heavy metal response
      in plants, animals and microorganisms.

PMID- 11952162
TI  - Effects of diabetes, vanadium, and insulin on glycogen synthase activation in
      Wistar rats.
AB  - In vivo effects of insulin and vanadium treatment on glycogen synthase (GS),
      glycogen synthase kinase-3 (GSK-3) and protein phosphatase-1 (PP1) activity were
      determined in Wistar rats with streptozotocin (STZ)-induced diabetes. The
      skeletal muscle was freeze-clamped before or following an insulin injection (5
      U/kg i.v.). Diabetes, vanadium, and insulin in vivo treatment did not affect
      muscle GSK-3beta activity as compared to controls. Following insulin stimulation
      in 4-week STZ-diabetic rats muscle GS fractional activity (GSFA) was increased 3
      fold (p < 0.05), while in 7-week diabetic rats it remained unchanged, suggesting
      development of insulin resistance in longer term diabetes. Muscle PP1 activity
      was increased in diabetic rats and returned to normal after vanadium treatment,
      while muscle GSFA remained unchanged. Therefore, it is possible that PP1 is
      involved in the regulation of some other cellular events of vanadium (other than
      regulation of glycogen synthesis). The lack of effect of vanadium treatment in
      stimulating glycogen synthesis in skeletal muscle suggests the involvement of
      other metabolic pathways in the observed glucoregulatory effect of vanadium.

PMID- 11952163
TI  - Mainstream and sidestream cigarette smoke exposure increases Ca2+-dependent
      phospholipid binding proteins in guinea pig alveolar type II cells.
AB  - We have earlier identified the presence of a 36 kDa Ca2+-dependent phospholipid
      binding protein (PLBP) in guinea pig alveolar type II cells. PLBP has been
      suggested to act as a mediator in facilitating and regulating intracellular
      surfactant assembly and delivery to the plasma membrane of type II cells for
      secretion into alveolar space. It has been reported that cigarette smoke exposure
      (CSE) causes a decrease in the surfactant activity in bronchial washings. We have
      also reported earlier that mainstream (MS) and sidestream (SS) CSE causes
      desensitization of beta-adrenoreceptors in guinea pig alveolar type II cells.
      Since both Ca2+ and beta-adrenoreceptors are involved in surfactant secretion and
      PLBP is involved in surfactant delivery, it is important to know whether CSE
      causes any change in the PLBP level in alveolar type II cells. In the present
      study, we have demonstrated that MS and SS CSE causes a significant increase in
      the levels of PLBP in alveolar type II cells (107 and 150%, respectively) and in
      lung lavage (42 and 125%, respectively) in comparison to that in sham control
      (430 ng/mg protein in alveolar type II cells and 780 ng/mg protein in lung
      lavage). The mechanism by which smoke exposure causes an elevation in the levels
      of PLBP in alveolar type II cells and lung lavage remains to be investigated.

PMID- 11952164
TI  - Down-regulation of ERK1 and ERK2 activity during differentiation of the
      intestinal cell line HT-29.
AB  - The role and regulation of signal transduction pathways in proliferation and
      differentiation of intestinal epithelial cells are still poorly understood.
      However, growing evidences have been recently accumulated demonstrating that
      mitogen-activated protein kinases (MAPKs) play a pivotal function in the normal
      development of intestine. We have investigated, in the intestinal cell line HT
      29, the regulation (namely activity and phosphorylation degree) of MAP kinases
      ERK 1 (p44) and ERK 2 (p42) during differentiation. Addition of fetal calf serum
      to HT-29 undifferentiated resting cells caused a rapid phosphorylation of both
      ERKs and an increase of their specific kinase activity. Moreover, nuclear
      translocation of ERK 1 and ERK 2 occurred concurrently to their activation,
      leading to the conclusion that ERK 1 and ERK 2 are classically regulated when
      quiescent HT-29 cells are induced to proliferate. Butyrate addition to the
      intestinal cell line resulted in terminal differentiation and in a selective down
      regulation of ERK 2 activity (and phosphorylation degree) without any effect on
      ERK 1. Conversely, when HT-29 cells were differentiated by repeated passages in a
      glucose-free medium, we observed a progressive dephosphorylation and inactivation
      of p42 and p44 kinases along with the failure of serum to activate both the
      enzymes. Our findings suggest that, during the differentiation of intestinal
      cells, remarkable changes occur in ERK 1 and ERK 2 control mechanisms leading to
      an unresponsiveness of MAP kinase pathway.

PMID- 11952166
TI  - Hydrogen peroxide enhances iron-induced injury in isolated heart and ventricular
      cardiomyocyte in rats.
AB  - To explore the cardiac effects of iron with or without hydrogen peroxide, the
      isolated perfused rat heart and enzymatically isolated ventricular cardiomyocyte
      were used. It was shown that treatment with cell-permeable iron (Fe-HQ) for 10
      min reduced the contractile amplitude and velocity and end diastolic cell length
      in the cardiomyocyte and increased the contents of lactate dehydrogenase (LDH)
      and creatine kinase (CK) in the coronary effluent and malondialdehyde (MDA) in
      the myocardium. The left ventricular developed pressure (LVDP), +/-dP/dtmax, and
      heart rate and coronary flow are showed a biphasic phase, an increase at first
      followed by a decline. Treatment with hydrogen peroxide for 10 min following Fe
      HQ augmented the effect of iron with an increase in coronary LDH and CK release
      and myocardial MDA content, and decrease in LVDP, +/-dP/dtmax and heart rate.
      Perfusion of reduced glutathione with hydrogen peroxide counteracted these
      effects of Fe-HQ and hydrogen peroxide while dimethyl sulfoxide had no effect on
      the injury induced by Fe-HQ and hydrogen peroxide in the isolated rat heart. This
      suggests that augmentation of myocardial injury as a result of an increase in
      intracellular iron by hydrogen peroxide might involve the dysfunction of
      sulfydryl group containing proteins but not the hydroxyl radicals.

PMID- 11952165
TI  - Insulin-like growth factor-induced hypertrophy of cultured adult rat
      cardiomyocytes is L-type calcium-channel-dependent.
AB  - The insulin-like growth factors-I and -II are potent growth stimulators in vivo
      and for many different cultured cells in vitro. Here IGF-I and -II are shown to
      directly induce hypertrophy of adult rat ventricular cardiomyocytes in serum-free
      medium as demonstrated by their increased size, total protein synthesis, and
      transcription of muscle-specific genes. The cells hypertrophied within 1 day when
      exposed to as little as 10(-11) M IGF-I or 10(-10) M IGF-II. With 10(-8) M IGF-I,
      cell size was significantly increased 34% by 1 day of culture and 57% by 2 days.
      With 10(-8) M IGF-II, cell size was similarly increased 32% by day 1 and 57% by 2
      days. During hypertrophy, total protein synthesis was increased 2.3-fold with IGF
      I and 2-fold with IGF-II. Gene expression for myosin light chain 2 and troponin I
      was upregulated with either growth factor. Hypertrophy induced by IGF-I was
      blocked by IGF binding protein-3, which binds IGF-I, while that induced by IGF-II
      was blocked by antibodies against IGF-II. Nicardipine, an inhibitor of L-type
      Ca2+-channels, completely blocked the hypertrophy induced by either IGF showing
      for the first time that such voltage-dependent channels are necessary for the
      hypertrophic effects of the IGFs on adult cardiomyocytes.

PMID- 11952167
TI  - Identification of TH1 as an interaction partner of A-Raf kinase.
AB  - A-Raf is an important intermediate of the growth factor Ras-MAP kinase pathway.
      In a two-hybrid screen of human fetal liver cDNA library, TH1 was detected as a
      new interaction partner of A-Raf. TH1 is a highly conserved and widely expressed
      protein, which was recently cloned by Bonthron DT group. The binding between A
      Raf and TH1 was specific, as no binding between TH1 and B-Raf or c-Raf was
      observed, and the amino-terminal 162 amino acids in the A-Raf regulatory domain
      were found to be sufficient for this interaction. This specific interaction may
      have played a critical role in the activation of A-Raf.

PMID- 11952169
TI  - Accumulation of plasma N-methyl-2-pyridone-5-carboxamide in patients with chronic
      renal failure.
AB  - Intracellular catabolism of NAD in mammalian cells occurs mainly via reaction
      catalyzed by poly(ADP-ribose) polymerase (PARP) with the release of nicotinamide,
      which is then metabolized predominantly to N-methyl-2-pyridone-5-carboxamide
      (2PY). PARP could be activated by binding to broken DNA and is known to be
      involved in DNA repair mechanisms, cell stress response and regulation of
      apoptosis. 2PY may accumulate under disease conditions resulting in accelerated
      DNA damage and retention of catabolic products. Our hypothesis was that chronic
      renal failure would lead to elevation of 2PY and potentially to inhibition of
      PARP and related physiological mechanisms. In the present study we: (a) compared
      plasma 2PY concentration in healthy subjects and in patients with chronic renal
      failure (CRF); (b) evaluated the relationship between plasma 2PY concentration
      and the severity of CRF; (c) evaluated the effect of hemodialysis treatment and
      kidney transplantation on 2PY concentration. We found that the plasma 2PY
      concentration in healthy subjects is 0.83+/-0.18 microM but it could increase up
      to 40 microM in patients with CRF. A significant correlation was found in CRF
      between plasma 2PY and creatinine concentration. A single hemodialysis treatment
      was associated with significant reduction of plasma 2PY concentration after the
      hemodialysis, but it increased rapidly 48 h after the end of treatment.
      Successful kidney transplantation was associated with return of 2PY concentration
      to the normal range. In conclusion, our results indicated significant production
      of 2PY in humans. In healthy subjects 2PY is cleared from the plasma by excretion
      in the urine. Altered excretion by the kidney leads to increase in plasma
      concentration of 2PY. It is possible that 2PY may play a significant role in the
      development of uremic toxemia, especially as an inhibitor of poly(ADP
      ribose)polymerase.

PMID- 11952168
TI  - Action of E. coli endotoxin, IL-1beta and TNF-alpha on antioxidant status of
      cultured hepatocytes.
AB  - We have previously reported that endotoxin induces in vivo oxidative stress in
      liver and a significant increase in hepatic and plasma glutathione concentrations
      during the acute phase of reversible endotoxic shock in rats. In the present
      study we examined the in vitro effects of E. coli 0111:B4 endotoxin
      (lipopolysaccharide, LPS), IL-1beta and TNF-alpha on antioxidant status of
      cultured hepatocytes in order to differentiate between the direct and mediated
      endotoxin action. LPS increased total glutathione (tGSH) levels after 2 h
      treatment but decreased oxidized glutathione (GSSG) content which lead to a
      marked decrease in GSSG/tGSH index. At shorter treatment times a biphasic and
      dose-dependent behaviour was observed. Cytokines (IL-1beta and TNF-alpha)
      produced significant decreases in tGSH and GSSG after 30 min treatment. Despite
      its prooxidant effect, TNF-alpha significantly reduced GSSG/tGSH index. Although
      no significant effects were observed on glutathione reductase activity, both LPS
      and cytokines induced an important inhibition of glutathione peroxidase which can
      justify the lipid peroxidation previously observed both in liver during
      reversible endotoxic shock and in cultured hepatocytes after treatment with
      endotoxin. The inhibition of hepatic glutathione peroxidase, besides the
      stimulation of GSH synthesis by LPS and GSH efflux by cytokines, guarantees the
      export of hepatic glutathione in its reduced form for other organs, contributing
      to the interorgan homeostasis. On the other hand, the results presented here
      support a new role for GSSG/tGSH index different from a mere indicator of
      oxidative stress.

PMID- 11952170
TI  - Infertility in mice induced by the rhesus monkey chorionic gonadotropin beta
      subunit glycoprotein (rmCGbeta) using DNA immunization.
AB  - The recombinant eukaryotic expression vector pCMV4-rmCGbeta, inserted full-length
      cDNA of the beta-subunit of rhesus monkey chorionic gonadotropin (rmCGbeta), as
      DNA immuno-contraceptive against CGbeta glycoprotein, has previously demonstrated
      the biological expression of rmCGbeta in vitro and in vivo. The plasmid DNA of
      pCMV4-rmCGbeta was inoculated into BALB/c mice at different doses and routes as
      DNA immuno-contraceptive to understand its antifertility effect. The results of
      immune responses indicated that the intradermal inoculation is the optimal pCMV4
      rmCGbeta DNA delivery method for BALB/c mice, and the dose of 10 microg should be
      enough to elicit immune response. With different doses from 10-50 microg, marked
      reductions in the fertility of the female mice after two intramuscular
      inoculations of pCMV4-rmCGbeta DNA were seen, while the similar level of humoral
      immune responses were induced. With the dose of 20 microg of pCMV4-rmCGbeta DNA,
      the mice showed reduction in fertility from intraperitoneal, and intradermal to
      intramuscular inoculating method. The antifertility effect of antiserum from
      immunized mice confirmed that the antibodies elicited by pCMV4-rmCGbeta DNA could
      prevent pregnancy in female mice. At the same time, the full-length cDNA of beta
      subunit of mouse chorionic gonadotropin (muCGbeta) was cloned from placenta and
      sequenced for the first time (GenBank Accession No. AF333067). Sequence analysis
      showed that muCGbeta shares 99.6% homology with rmCGbeta and 90.6% with hCGbeta
      respectively. The results indicated that the infertility of BALB/c mice induced
      by pCMV4-rmCGbeta contraceptive should be further studied as a CGbeta DNA
      contraceptive. (Mol Cell Biochem 231: 89-96, 2002)

PMID- 11952171
TI  - Maternal-fetal transport kinetics of copper, selenium, magnesium and iron in
      perfused human placental lobule: in vitro study.
AB  - Transport characteristics of certain inorganic elements such as copper,
      magnesium, selenium and iron have been studied in maternal-fetal direction in
      normal pregnancies, using in vitro perfusion of isolated placental lobules.
      Copper, selenium, magnesium and iron salts corresponding to twice physiological
      concentrations were injected as a 100 microl bolus, into the maternal arterial
      perfusate. Serial perfusate samples were collected from venous outflows for a
      study period of 5 min. Concentrations of various inorganic elements and their
      transport kinetics were determined. Transport fractions of copper, selenium,
      magnesium and iron averaged 0.14, 0.19, 0.06 and 0.23% of maternal load
      respectively. The pharmacokinetic parameters such as area under the curve,
      clearance, elimination constant, and time for maximum response showed some
      significant differences between the various elements. We speculate that copper
      and selenium share the same transport pathway along a concentration gradient in
      maternal-fetal direction, while for iron and magnesium, active transport plays a
      predominant role for element transfer across the human placental membrane.

PMID- 11952173
TI  - Hydraulic properties and leachate level analysis of Kimpo metropolitan landfill,
      Korea.
AB  - Hydraulic properties of waste and cover soil from Kimpo Metropolitan Landfill
      were experimentally measured by laboratory tests. The degree of compaction was
      changed to identify the effect on hydraulic conductivity, field capacity, and
      permanent wilting point. Properties were utilized in developing a reliable
      numerical tool for leachate analysis. HELP, a simulation model for hydrologic
      evaluation of landfill performance, was adopted for that purpose. For
      calibration, results from simulation using the parameter values measured by
      laboratory tests were compared against the field data. The model was applied to
      predict the leachate level change according to the degree of compaction and cover
      soil thickness variation. It was found that the increase in the degree of
      compaction for intermediate cover soil and waste results in the decrease of field
      capacity and hydraulic conductivity, hence, the increase of leachate level. The
      effect of cover layer thickness on the leachate level was minor. Based on the
      findings from laboratory and numerical experiments, a guideline for reclamation
      practice was recommended.

PMID- 11952172
TI  - Protein kinase Calpha is a calpain target in cultured embryonic muscle cells.
AB  - Previously we isolated a micro-calpain/PKCalpha complex from skeletal muscle
      which suggested tight interactions between the Ca2+-dependent protease and the
      kinase in this tissue. Our previous studies also underlined the involvement of
      ubiquitous calpains in muscular fusion and differentiation. In order to precise
      the relationships between PKCalpha and ubiquitous calpains in muscle cells, the
      expression of these two enzymes was first examined during myogenesis of embryonic
      myoblasts in culture. Our results show that calpains and PKCalpha are both
      present in myotubes and essentially localized in the cytosolic compartment.
      Moreover, calpains were mainly present after 40 h of cell differentiation
      concomitantly with a depletion of PKCalpha content in the particulate fraction
      and the appearance of PKMalpha fragment. These results suggest a possible calpain
      dependent down-regulation process of PKCalpha in our model at the time of intense
      fusion. In our experimental conditions phorbol myristate acetate (PMA) induced a
      rapid depletion of PKCalpha in the cytosolic fraction and its translocation
      toward the particulate fraction. Long term exposure of myotubes in the presence
      of PMA induced down-regulation of PKCalpha, this process being partially blocked
      by calpain inhibitors (CS peptide and inhibitor II) and antisense
      oligonucleotides for the two major ubiquitous calpain isoforms (m- and micro
      calpains). Taken together, our findings argue for an involvement of calpains in
      the differentiation of embryonic myoblasts by limited proteolytic cleavage of
      PKCalpha.

PMID- 11952174
TI  - Temporal variation of leachate quality from pre-sorted and baled municipal solid
      waste with high organic and moisture content.
AB  - Landfill leachate characterization is a critical factor in establishing a
      corresponding effective management strategy or treatment process. However, it is
      often difficult to forecast leachate quality because of a variety of influencing
      factors such as waste composition and landfill operations. This paper describes
      leachate formation mechanisms, summarizes leachate quality indicators, and
      investigates the temporal variation of leachate quality from pre-sorted and baled
      municipal solid waste characterized with high organic and moisture content. The
      purpose of the study is to evaluate the potential effects of waste composition
      and site-specific operational procedures on biodegradation processes and leachate
      quality at a field-scale landfill that receives in excess of 1800 tonnes per day
      of refuse. For this purpose, waste disposal and leachate generation rates were
      monitored and leachate samples were collected for a period of 18 months during
      the early stages of refuse deposition. Chemical analysis was performed on the
      samples and the temporal variation of several parameters were monitored including
      pH, COD, TOC, TDS, chlorides, sulfates, orthophosphates, nitrates, ammonia
      nitrogen, hardness, and heavy metals. Chemical concentration levels were related
      to biological activity within the landfill and the results indicated that: (1)
      pre-sorting and baling of the waste did not hinder waste stabilization; and (2)
      the high organic and moisture contents resulted in an extremely strong leachate,
      particularly at the onset of biodegradation processes, which can affect the
      leachate treatment facility.

PMID- 11952175
TI  - Biotransformation of explosive-grade nitrocellulose under denitrifying and
      sulfidogenic conditions.
AB  - Waste nitrocellulose (NC) is regulated as a hazardous material. The objective of
      this study was to determine if NC exposed to denitrifying and sulfidogenic
      conditions would undergo sufficient removal of the nitro groups to yield a
      material that is no longer explosive. Enrichment cultures were established with
      methanol as the electron donor for nitrate-reducing conditions and lactate for
      sulfate-reducing conditions. NC was added to the cultures at 10 g/l. A
      statistically significant decrease in the nitrogen (N) content of NC occurred in
      both enrichment cultures, from approximately 13.1-13.2% in virgin NC to 12.2
      12.4%. This was accompanied by an increase in nitrogen gas formation. The
      presence of a primary substrate (methanol and lactate) was necessary to affect
      this change; NC itself did not serve as an electron donor. In cultures that were
      carrying out denitrification but were then depleted of nitrate, with methanol
      still present, a slightly greater removal of nitro groups from NC occurred along
      with additional formation of nitrogen gas. NC did not have an inhibitory affect
      on the denitrification process but it did significantly slow the rate of lactate
      consumption and sulfate reduction. Fourier Transform Infrared Spectroscopy (FTIR)
      results indicated that NC exposed to denitrifying conditions was enriched in
      hydroxyl groups, consistent with removal of some of the nitro groups by
      hydrolysis of the nitrate esters. NC exposed to nitrate- and sulfate-reducing
      conditions and virgin NC were also compared based on their explosive properties
      using a small-scale burning test. The biologically treated NC exhibited somewhat
      less reactivity, but was still rated as explosive. The decrease in%N, increase in
      N2, and FTIR results demonstrated that NC does undergo biotransformation in the
      presence of nitrate- and sulfate-reducing enrichment cultures, but the extent of
      denitration does not appear to be adequate to yield a nonhazardous product.

PMID- 11952177
TI  - Chemical speciation of carbon in municipal solid waste incinerator residues.
AB  - Incinerators do not achieve a complete mineralization of organic constituents of
      municipal solid waste. The solid residues (bottom ash, boiler ash and air
      pollution control residues) contain carbon which can be determined as total
      organic carbon (TOC). This work focuses on the TOC composition and its
      significance to the genesis and diagenesis of the solid residues. An analytical
      procedure is presented to characterize carbon species by different chemical and
      microscopic analytical methods. The procedure is based on two steps. In the first
      step a quantitative classification of TOC into four different carbon species
      (elemental carbon, water extractable organic carbon, dichloromethane extractable
      organic carbon and non extractable organic carbon) is performed to obtain a first
      survey of the TOC composition. Based on this survey a further characterization of
      individual carbon species is performed. The results of the qualitative and
      quantitative characterization of carbon species allow to postulate hypotheses on
      the influence of organic carbon on the long-term behavior of the solid residues.

PMID- 11952176
TI  - Rapid-extraction oxidation process to recover and reuse copper chromium and
      arsenic from industrial wood preservative sludge.
AB  - Chromated copper arsenate (CCA) wood preservative can form insoluble sludges when
      the hexavalent chromium component is reduced by wood extractives, wood particles
      and preservative additives in the solution. This sludge accumulates in treating
      solution work tanks, sumps and in-line filters and must be disposed of as
      hazardous wastes by waste disposal companies at high costs. A number of
      commercial sludges were investigated and found to contain 18-94% copper, chromium
      and arsenic as oxides combined with sand, oil, wood particles, additives and wood
      extractives. We have developed a multi-stage recycling process whereby
      approximately 97% of the CCA components are recovered from the sludge. It
      involves extraction with sodium hypochlorite to remove and oxidize chromium (more
      than 90%) and extract most of the arsenic (approx. 80%) followed by extraction of
      the copper and remaining arsenic and chromium with phosphoric acid. The
      phosphoric acid extract contains some trivalent chromium, which is subsequently
      oxidized by sodium hypochlorite. The combined oxidized extract containing CrVI,
      CuII and AsV was compatible with CCA treating solutions and could be re-used
      commercially for treating wood without having a significant effect on the
      preservative fixation rate or the leach resistance of the treated wood. A cost
      analysis showed that the economic savings from recovery of CCA chemicals and
      reduced landfill costs exceeded the variable costs for materials and energy for
      the process by as much as Can $966 per tonne of sludge if sodium sulfite can be
      acquired in bulk quantities for the process.

PMID- 11952178
TI  - Effects of limestone addition and sintering on heavy metal leaching from
      hazardous waste incineration slag.
AB  - Hazardous waste incineration (HWI) in rotary kilns and the disposal of the
      residual slag on landfills play an important role in German waste treatment. In
      order to save disposal costs the elution behaviour of HWI-slag should be further
      optimised. Quality-improved slag may be disposed off on cheaper landfill sites
      still applying to landfill regulations. In a new process-integrated approach
      hazardous waste is mixed with limestone, which initiates chemical reactions with
      heavy metals in the rotary kiln yielding new compounds of different solubility.
      In this work HWI-slag/limestone mixtures are thermally treated and then examined
      by elution tests. Experimental data indicate that the heavy metals pertinent to
      landfill class assignment of a HWI-slag share a solubility minimum at a CaO
      content of about 15%. Such improved HWI-slags are allowed to be disposed off on
      cheaper landfill sites. Furthermore, a new combination of thermodynamic
      calculation methods is applied to predict heavy metal solubility for different
      process conditions. Used models hold the opportunity to explain the tendencies of
      heavy metal leaching and propose plausible chemical reactions. With it, a new
      tool to examine the impact of temperature treatment and slag composition on heavy
      metal elution from HWI-slag is presented.

PMID- 11952179
TI  - Sulfur polymer solidification/stabilization of elemental mercury waste.
AB  - Elemental mercury, contaminated with radionuclides, presents a waste disposal
      problem throughout the Department of Energy complex. In this paper we describe a
      new process to immobilize elemental mercury wastes, including those contaminated
      with radionuclides, in a form that is non-dispersible, will meet EPA leaching
      criteria, and has low mercury vapor pressure. In this stabilization and
      solidification process, elemental mercury is combined with an excess of powdered
      sulfur polymer cement (SPC) and sulfide additives in a mixing vessel and heated
      to approximately 40 degrees C for several hours, until all of the mercury is
      converted into mercuric sulfide (HgS). Additional SPC is then added and the
      temperature of the mixture raised to 135 degrees C, resulting in a molten liquid
      which is poured into a mold where it cools and solidifies. The final treated
      waste was characterized by powder X-ray diffraction and found to be a mixture of
      the hexagonal and orthorhombic forms of mercuric sulfide. The Toxicity
      Characteristic Leaching Procedure was used to assess mercury releases, which for
      the optimized process averaged 25.8 microg/l, with some samples being well below
      the new EPA Universal Treatment Standard of 25 microg/l. Longer term leach tests
      were also conducted, indicating that the leaching process was dominated by
      diffusion. Values for the effective diffusion coefficient averaged 7.6x10(-18)
      cm2/s. Concentrations of mercury vapor from treated waste in equilibrium static
      headspace tests averaged 0.6 mg/m3.

PMID- 11952180
TI  - An ecotoxic risk assessment of residue materials produced by the plasma
      pyrolysis/vitrification (PP/V) process.
AB  - Plasma is the fourth state of matter, following the three states of solid, liquid
      and gas. Experience has amply demonstrated that solids exposed to the oxygen
      deficient plasma flame are converted to liquid, and liquid exposed to the same
      flame is converted to gas. A low amount of vitrified solid residue material
      usually remains at the end of this process. Plasma pyrolysis/vitrification (PP/V)
      has been demonstrated as a safe, efficient, cost-effective technology for the
      treatment of wastes, including hazardous wastes. Besides the low amounts of
      gaseous byproducts that PP/V produces, the solid vitrified residue presents a low
      leachability of pollutants. Studies have been performed in many countries in
      order to assess the leachability of chemical substances. But from the results of
      identified studies, none has reported results on the ecotoxicological properties
      of the leachates. The aim of this study was to contribute to the assessment of
      ecotoxic risk of four different vitrified materials. Vitrified samples of
      contaminated soils, municipal solid wastes, and incinerator bottom ashes were
      submitted to the European leaching pre-standard test number prEN 12457-2. The
      leachates were analyzed for 22 chemical parameters. The biological
      characterization comprised the assessment of bioluminescence inhibition of
      Photobacterium phosphoreum bacterium, growth inhibition of Pseudokirchneriella
      subcapitata algae and the germination inhibition of Lactuca sativa vegetable. The
      chemical and ecotoxicological results were analyzed according to the French
      proposal of Criteria on the Evaluation Methods of Waste Toxicity (CEMWT) and a
      Toxicity Classification System (TCS). The chemical and ecotoxicological results
      indicated a low leachability of pollutants and a low toxicity level of leachates.
      All samples studied were as below the TCS class 1 level (no significant toxicity
      observed) and as non-ecotoxic for CEMWT. Therefore, the environmental ecotoxic
      risk of the analyzed vitrified samples was determined to be very low.

PMID- 11952181
TI  - The effect of solvent concentration on the use of palladized-iron for the step
      wise dechlorination of polychlorinated biphenyls in soil extracts.
AB  - This report describes the application of palladized iron (Pd/Fe) to the
      dechlorination of polychlorinted biphenyls (PCBs) at ambient temperature.
      Experiments supported by congener-specific analyses demonstrated that
      dechlorination occurs in a step-wise fashion with the meta-chlorines being more
      reactive than ortho-chlorines. Over the course of the laboratory experiments,
      complete conversion to biphenyl was observed. The process was also tested with
      PCBs dissolved in high (40-60%) concentrations of ethanol and isopropanol as a
      means of simulating solutions generated by commercial soil and solid waste
      extraction processes. The reaction rate was sensitive to the percentage of
      solvent but complete dechlorination was still indicated. Tests with soil extracts
      from a contaminated site demonstrated that there were no apparent interferences
      from asphalt and other miscellaneous debris. Short-duration tests with highly
      contaminated PCB solutions from a hazardous waste site demonstrated efficient
      dechlorination although there was a reduction in reaction rate with time.

PMID- 11952183
TI  - Arsenic adsorption from aqueous solutions by activated red mud.
AB  - Heat treatment and acid treatment methods have been tested on red mud to increase
      its arsenic adsorption capability. The results indicate that the adsorptive
      capacity of red mud can be increased by acid treatment. This treatment causes
      sodalite compounds to leach out. As(III) and As(V) adsorption characteristics of
      activated red mud have similar tendencies with raw red mud. Batch adsorption
      studies have shown that activated red mud in dosages ranging from 20 to 100 g l(
      1) can be used effectively to remove arsenic from aqueous solutions. The process
      is pH dependent, the optimum range being 5.8-7.5 for As(III) and 1.8-3.5 for
      As(V). The maximum removals are 96.52% for As(V) and 87.54% for As(III) for
      solutions with a final pH of 7.25 and 3.50, respectively, for the initial arsenic
      concentration of 133.5 micromol l(-1) (10 mg l(-1)), activated red mud dosage of
      20 g l(-1), contact time of 60 min and temperature of 25 degrees C. The
      adsorption data obtained follow a first-order rate expression and fit the
      Langmuir isotherm well. Isotherms have been used to obtain the thermodynamic
      parameters. It was found that the adsorption of As(III) was exothermic, whereas
      As(V) adsorption was endothermic.

PMID- 11952182
TI  - Sonochemical degradation of aromatic organic pollutants.
AB  - This work examines the use of ultrasound to mineralize 4-chlorophenol, 2,4
      dichlorophenol, [aryl-2H3]2,4-dichlorophenol, 4-chloro-3,5-dimethylphenol, 4
      fluorophenol, 2,4,6-trinitrotoluene, 2-amino-4,6-dinitrotoluene and 4-amino-2,6
      dinitrotoluene in dilute aqueous solution. Mineralization rates were determined
      as a function of substrate structure and concentration, bulk phase temperature,
      pH and the presence of co-solutes such as detergents and humic acids. All
      substrates were found to degrade sonochemically, as evidenced by the release of
      Cl- and NO3- respectively. Product analyses by GC-MS, HPLC, and micellar
      electrokinetic capillary chromatography (MECC) indicated mineralization with
      little formation of organic byproducts, a significant advantage over other
      remediation methods. Chloride release from chlorophenols was approximately
      proportional to substrate total chlorine content, irrespective of structural
      differences, and reached 80% of the theoretical limit. Fluoride release from 4
      fluorophenol was ca. 10-fold lower than that of chloride from 4-chlorophenol.
      Changes in the bulk phase temperature from 9.5 to 34 degrees C, and 12.5 to 30
      degrees C, respectively, were of little consequence to observed mineralization
      rates for nitroaromatics and chlorophenols. A significant mineralization rate
      increase resulted from sonication of 4-chlorophenol in acidified media. Additions
      of amphiphilic co-solutes resulted in modest, but statistically significant,
      sonolysis enhancements.

PMID- 11952184
TI  - The management of solid wastes.

PMID- 11952185
TI  - Cognitive-behavioral therapy for bulimia nervosa: time course and mechanisms of
      change.
AB  - Cognitive-behavioral therapy (CBT) is an effective treatment of bulimia nervosa,
      but its mechanisms of action have not been established. In this study the authors
      analyzed the results of a randomized control trial comparing CBT with
      Interpersonal Psychotherapy (IPT) to identify possible mediators of change of CBT
      for BN and its time course of action. Reduction in dietary restraint as early as
      Week 4 mediated posttreatment improvement in both binge eating and vomiting.
      Measures of self-efficacy concerning eating behavior, negative affect, and body
      shape and weight at midtreatment were also significantly associated with
      posttreatment outcome at 20 weeks. No evidence was found that the therapeutic
      alliance mediated treatment outcome. CBT had a significantly more rapid treatment
      effect than IPT, with 62% of posttreatment improvement evident by Week 6.

PMID- 11952186
TI  - Metacognitive awareness and prevention of relapse in depression: empirical
      evidence.
AB  - Metacognitive awareness is a cognitive set in which negative thoughts/feelings
      are experienced as mental events, rather than as the self. The authors
      hypothesized that (a) reduced metacognitive awareness would be associated with
      vulnerability to depression and (b) cognitive therapy (CT) and mindfulness-based
      CT (MBCT) would reduce depressive relapse by increasing metacognitive awareness.
      They found (a) accessibility of metacognitive sets to depressive cues was less in
      a vulnerable group (residually depressed patients) than in nondepressed controls;
      (b) accessibility of metacognitive sets predicted relapse in residually depressed
      patients; (c) where CT reduced relapse in residually depressed patients, it
      increased accessibility of metacognitive sets; and (d) where MBCT reduced relapse
      in recovered depressed patients, it increased accessibility of metacognitive
      sets. CT and MBCT may reduce relapse by changing relationships to negative
      thoughts rather than by changing belief in thought content.

PMID- 11952187
TI  - A component analysis of cognitive-behavioral therapy for generalized anxiety
      disorder and the role of interpersonal problems.
AB  - Clients with generalized anxiety disorder (GAD) received either (a) applied
      relaxation and self-control desensitization, (b) cognitive therapy, or (c) a
      combination of these methods. Treatment resulted in significant improvement in
      anxiety and depression that was maintained for 2 years. The large majority no
      longer met diagnostic criteria; a minority sought further treatment during follow
      up. No differences in outcome were found between conditions; review of the GAD
      therapy literature suggested that this may have been due to strong effects
      generated by each component condition. Finally, interpersonal difficulties
      remaining at posttherapy, measured by the Inventory of Interpersonal Problems
      Circumplex Scales (L. E. Alden, J. S. Wiggins, & A. L. Pincus, 1990) in a subset
      of clients, were negatively associated with posttherapy and follow-up
      improvement, suggesting the possible utility of adding interpersonal treatment to
      cognitive-behavioral therapy to increase therapeutic effectiveness.

PMID- 11952188
TI  - Community clinic treatment of depressed youth: benchmarking usual care against
      CBT clinical trials.
AB  - This study used a benchmarking strategy to evaluate the effectiveness of
      community psychotherapy for depressed youth relative to evidence-based treatment
      in clinical trials. Symptom trajectories of depressed youth treated in community
      mental health centers (CMHCs) were compared with trajectories of youth treated
      with cognitive-behavioral therapy (CBT) in clinical trials. Overall, outcomes of
      CMHC youth more closely resembled those of control condition youth than youth
      treated with CBT. Within the CMHC sample, ethnic minority status and low therapy
      dose were related to worse outcomes. However, when outcomes for Caucasian youth
      and youth receiving longer term services were examined, the CMHC sample still
      performed more poorly than youth treated with CBT. The findings support the value
      of developing, testing, and exporting effective therapies for depressed youth to
      community clinic settings.

PMID- 11952189
TI  - Risk and protective factors for suicidal behavior in abused African American
      women.
AB  - This study examined risk and protective factors that differentiate low-income,
      abused African American women (N = 200) who attempted suicide from those who had
      never made a suicide attempt. Results from multivariate analyses revealed that
      numerous and/or severe negative life events, a history of child maltreatment,
      high levels of psychological distress and depression, hopelessness about the
      future, and alcohol and drug problems were factors associated with attempter
      status. Protective factors associated with nonattempter status included
      hopefulness, self-efficacy, coping skills, social support, and effectiveness in
      obtaining material resources. Culturally competent intervention approaches for
      abused women should target increasing their protective factors and reducing their
      risk factors to decrease the likelihood that these women engage in suicidal
      behavior.

PMID- 11952190
TI  - Effects of methylphenidate and expectancy on children with ADHD: behavior,
      academic performance, and attributions in a summer treatment program and regular
      classroom settings.
AB  - Pharmacological and expectancy effects of 0.3 mg/kg methylphenidate on the
      behavior and attributions of boys with attention-deficit/hyperactivity disorder
      were evaluated. In a within-subject, balanced-placebo design, 136 boys received 4
      medication-expectancy conditions. Attributions for success and failure on a daily
      report card were gathered. Assessments took place within the setting of a summer
      treatment program and were repeated in boys' regular classrooms. Expectancy did
      not affect the boys' behavior; only active medication improved their behavior.
      Boys attributed their success to their effort and ability and attributed failure
      to task difficulty and the pill, regardless of medication and expectancy. Results
      were generally equivalent across the two settings; where there were differences,
      beneficial effects of medication were more apparent in the school setting. The
      findings were unaffected by individual-difference factors.

PMID- 11952191
TI  - Alcohol dependence and abuse in three groups at varying familial alcoholism risk.
AB  - Three groups of young men varying in familial alcoholism risk were compared for
      lifetime and current Diagnostic and Statistical Manual of Mental Disorders (4th
      ed.; DSM-IV; American Psychiatric Association, 1994) diagnoses. A withdrawal gate
      diagnostic model (WGM) requiring withdrawal for a dependence diagnosis was also
      evaluated. Extremely high lifetime DSM-IV diagnostic rates were found for all
      groups (> or = 78%), with the highest rate in the highest risk group. Similar
      group differences obtained for individual criteria or symptoms. Although lifetime
      diagnostic rates were similar for the WGM and DSM-IV, virtually all cases of
      dependence were preceded by abuse for the WGM, unlike DSM-IV. The findings
      underline the importance of distinguishing degrees of familial alcoholism risk.
      The WGM model temporal onset findings versus DSM-IV and the high lifetime
      diagnostic rates obtained suggest some limitations of the DSM-IV diagnoses.

PMID- 11952192
TI  - Behavioral couples therapy for female substance-abusing patients: effects on
      substance use and relationship adjustment.
AB  - Married or cohabiting female drug-abusing patients (N = 75) were randomly
      assigned to either a behavioral couples therapy condition (BCT; n = 37), which
      consisted of group, individual, and behavioral couples therapy sessions, or to an
      equally intensive individual-based treatment condition (IBT; n = 38), which
      consisted of group and individual counseling. During most of the 1-year follow
      up, compared with participants who received IBT, those who received BCT reported
      (a) fewer days of substance use, (b) longer periods of continuous abstinence, (c)
      lower levels of alcohol, drug, and family problems, and (d) higher relationship
      satisfaction. However, differences in relationship satisfaction and number of
      days of substance use dissipated over the course of the posttreatment follow-up
      period and were not significantly different by the end of 1 year.

PMID- 11952193
TI  - Patterns of change in depressive symptoms during smoking cessation: who's at risk
      for relapse?
AB  - The authors examined patterns of change in depressive symptoms during smoking
      cessation treatment in 163 smokers with past major depressive disorder (MDD).
      Cluster analysis of Beck Depression Inventory (A. T. Beck, C. H. Ward, M.
      Mendelson, J. Mock, & J. Erbaugh, 1961) scores identified 5 patterns of change.
      Although 40% of participants belonged to clusters characterized by increasing
      depressive symptoms during quitting (rapid increasers, n = 31, and delayed
      increasers, n = 35), almost 47% were in clusters characterized by decreasing
      symptoms (delayed decreasers, n = 24, and rapid decreasers, n = 52). Both rapid
      and delayed increasers had especially poor smoking cessation outcomes. Results
      suggest that among smokers with an MDD history there is substantial heterogeneity
      in patterns of depressive symptoms during quitting and that patterns involving
      increased symptoms are associated with low abstinence rates.

PMID- 11952194
TI  - Predictors of participation and attrition in a health promotion study involving
      psychiatric outpatients.
AB  - Participant selection biases can reduce the generalizability of research findings
      and lead to misestimates of intervention effectiveness. The authors examined
      factors associated with study participation and attrition among psychiatric
      outpatients recruited for the initial phase of a health promotion trial. Medical
      records were reviewed to obtain HIV-risk and substance abuse data, as well as
      psychiatric and demographic characteristics of potential participants. Of 895
      eligible outpatients, 67% (n = 601) consented to participate, among whom 69% (n =
      415) completed all baseline appointments. Compared with nonconsenters, consenters
      were more likely to be at risk for drug problems and to receive care from clinics
      serving more impaired patients. Study completion was associated with older age, a
      psychiatric diagnosis other than adjustment disorder, and a recent sexually
      transmitted disease diagnosis. These findings suggest that patients who could
      most benefit from risk reduction interventions are more likely to participate.

PMID- 11952195
TI  - Self-definition as a survivor of childhood sexual abuse among navy recruits.
AB  - This study explored how specific childhood sexual experiences (CSEs) might be
      related to self-identification as a victim of sexual abuse and to gender
      differences in self-defined victimization. Hierarchical logistic regression was
      used to estimate the relationship of demographic and CSE characteristics with
      self-definitions. The characteristics most strongly associated were threats
      force, incest, and younger age at the time of the experience. Men were less
      likely than were women to acknowledge abuse and to report CSE characteristics
      indicative of abuse. Women were more likely to identify themselves as victims the
      more CSEs they reported involving sexual penetration. Finally, in an analysis of
      familial abuse, men were more likely to define themselves as victims if the
      perpetrator was also male.

PMID- 11952196
TI  - Do places matter? Socioeconomic disadvantage and behavioral problems of children
      in Canada.
AB  - This study evaluated the influence of neighborhoods and socioeconomic
      disadvantage on behavioral problems rated by parents and teachers in a nationally
      representative sample of children ages 4 to 11 years living in Canada. Between
      neighborhood variation accounted for 7.6% and 6.6% of parent and teacher ratings,
      respectively. About 25.0% of this neighborhood variation could be explained by
      socioeconomic variables evenly divided between neighborhood and family-level
      measures. Family socioeconomic status, lone-parent family status, and percentage
      of lone parents in neighborhoods were strong, reliable predictors of behavioral
      problems. Ratings were contextualized: Fewer behavioral problems were assessed in
      children from well-off families living in disadvantaged neighborhoods, whereas
      more problems were assessed in children from poor families living in advantaged
      neighborhoods.

PMID- 11952197
TI  - Effects of extinction context and retrieval cues on alcohol cue reactivity among
      nonalcoholic drinkers.
AB  - Pavlovian conditioning models have influenced the development of cue exposure
      treatments for drug abuse. However, poor maintenance of extinction performance
      (renewal) after treatment is a common problem. A treatment-analogue experiment
      tested the role of context in renewal, as well as a potential strategy for
      reducing renewal. Seventy-eight social drinkers completed extinction trials to
      reduce saliva and urge reactivity to alcohol cues and were randomly assigned to a
      renewal test in either the same context as extinction, a different context, or
      the different context containing a cue from the extinction context (E-cue). As
      predicted, the different context produced greater renewal than the same context
      and renewal was attenuated when the E-cue was present. These results offer
      preliminary evidence for the context dependence of extinction to alcohol cues and
      for the use of an extinction cue to improve the generalizability of exposure
      therapies.

PMID- 11952198
TI  - Low-cost contingency management for treating cocaine- and opioid-abusing
      methadone patients.
AB  - This study evaluated the efficacy of a low-cost contingency management (CM)
      procedure in reducing concurrent cocaine and opioid use among methadone patients.
      Forty-two patients were randomly assigned to 12 weeks of standard treatment or
      standard treatment plus CM. CM patients eamed the opportunity to draw from a bowl
      and win prizes ranging from $1 to $ 100 in value for submitting samples negative
      for cocaine and opioids. Patients in the CM condition achieved longer durations
      of continuous abstinence than patients in the standard treatment condition, and
      these effects were maintained throughout a 6-month follow-up period. On average,
      patients in the CM condition earned $137 of prizes. These data suggest that this
      prize reinforcement procedure may be suitable for community-based settings.

PMID- 11952199
TI  - Resolving unfinished business: relating process to outcome.
AB  - This study related the process of the resolution of unfinished business with a
      significant other to therapeutic outcome in a population of 26 clients who
      suffered from various forms of interpersonal problems and childhood maltreatment.
      Clients were treated in emotion-focused, experiential therapy with gestalt empty
      chair dialogues. Those clients who expressed previously unmet interpersonal needs
      to the significant other, and manifested a shift in their view of the other, had
      significantly better treatment outcomes. The presence of the specific process of
      resolution in the clients' empty-chair dialogues was also found to be a better
      predictor of outcome than the working alliance. Degree of emotional arousal was
      found to discriminate between resolvers and nonresolvers.

PMID- 11952200
TI  - Couples- versus individual-based therapy for alcohol and drug abuse: effects on
      children's psychosocial functioning.
AB  - The study compared the effect of couples-based versus individual-based therapy
      for men who entered outpatient substance abuse treatment on the psychosocial
      functioning of children in their homes. Men were randomly assigned to (a)
      behavioral couples therapy (BCT), (b) individual-based treatment (IBT), or (c)
      couples-based psychoeducational attention control treatment (PACT). For both
      children of alcohol--(N = 71) and drug-abusing men (N = 64), parents' ratings of
      children's psychosocial functioning was higher for children whose fathers
      participated in BCT at posttreatment and at 6- and 12-month follow-up than for
      children whose fathers participated in IBT or PACT. BCT resulted in greater
      improvements in parents' dyadic adjustment and fathers' substance use. Thus,
      couples-based intervention that addresses both issues may have greater benefits
      for children in these homes.

PMID- 11952201
TI  - Twelve-month follow-up of virtual reality and standard exposure therapies for the
      fear of flying.
AB  - This study reports the 12-month follow-up from patients with the fear of flying
      who were treated in a controlled study and randomly assigned (n = 49) to virtual
      reality exposure (VRE) therapy, standard exposure (SE) therapy, or to a wait-list
      control (WL). VRE and SE were equally superior to WL. At 12 months posttreatment,
      data were gathered on 24 of the 30 (80%) patients who were assigned to VRE or SE.
      Patients maintained their treatment gains, and 92% of VRE participants and 91% of
      SE participants had flown on a real airplane since the graduation flight. This is
      the 1st year-long follow-up of patients having been treated with VRE and
      indicates that short-term treatment can have lasting effects.

PMID- 11952202
TI  - Adjustment to a dyadic stressor: a longitudinal study of coping and depressive
      symptoms in infertile couples over an insemination attempt.
AB  - In a study designed to examine how intimate partners' coping processes with
      regard to infertility predicted depressive symptoms across the course of a
      treatment cycle, 43 couples completed assessments in the week prior to and the
      week after receiving a negative pregnancy result from an alternate insemination
      attempt by the partner. Depressive symptoms in both partners increased
      significantly after the pregnancy result receipt. As hypothesized, avoidant
      coping predicted increased distress over time. and approach-oriented coping
      (e.g., problem-focused coping, emotional processing, and expression) predicted
      decreased distress. Coping strategies engaged in by both individuals and partners
      predicted depressive symptoms, and for women, interactions also emerged between
      their own and their partners' coping.

PMID- 11952203
TI  - When youth mental health care stops: therapeutic relationship problems and other
      reasons for ending youth outpatient treatment.
AB  - Child and adolescent treatment ends for a variety of reasons, but little is known
      about the underlying factors or about whether any such factors are linked to
      premature dropout. To address these gaps, the authors administered their Reasons
      for Ending Treatment Questionnaire (RETQ) to the parents of 344 referred youth
      (aged 7-18 years), from 10 clinics, who had ended outpatient treatment. A factor
      analysis identified six factors, all showing good test-retest reliability and
      internal consistency. One of these, Therapeutic Relationship Problems, accounted
      for the most variance (16%) and was the only factor, other than Money Issues,
      that distinguished therapy dropouts from completers. The findings highlight major
      themes underlying decisions to end child therapy, and they highlight the
      importance of the therapeutic relationship.

PMID- 11952204
TI  - Sudden gains in recovering from depression: are they also found in
      psychotherapies other than cognitive-behavioral therapy?
AB  - Following T. Z. Tang and R. J. DeRubeis's (1999) report of sudden gains (a sudden
      and substantial improvement in depression symptoms in one between-session
      interval) in cognitive-behavioral therapy (CBT) for depression, this study
      explored sudden gains in supportive-expressive (SE) psychotherapy. Studies
      suggested that CBT sudden gains are caused by cognitive changes, which is a
      factor specific to CBT. Thus, sudden gains might not be expected in SE
      psychotherapy. Contrary to that expectation, sudden gains in SE psychotherapy
      were found, and they showed similar magnitude, affected a similar percentage of
      patients, and occurred at about the same time in treatment as CBT sudden gains.
      However, the symptom gains from the SE psychotherapy sudden gains were much less
      stable than the CBT sudden gains and showed a much higher rate of reversal before
      treatment ended. The long-term benefits of SE psychotherapy sudden gains also
      appear less robust than CBT sudden gains.

PMID- 11952205
TI  - "Comparison of culture media, simplate, and petrifilm for enumeration of yeasts
      and molds in food," a comment on: J. Food Prot. 64(10):1592-1596 (2001).

PMID- 11952206
TI  - Detection of Escherichia coli O157:H7 in 10- and 25-gram ground beef samples with
      an evanescent-wave biosensor with silica and polystyrene waveguides.
AB  - A portable evanescent-wave fiber-optic biosensor was used to detect Escherichia
      coli O157:H7 in seeded 10- and 25-g ground beef samples. The biosensor works by
      launching light from a 635-nm laser diode into specially designed optical fiber
      probes, generating an evanescent field that extends approximately 1,000 nm from
      the fiber surface. Fluorescent molecules within the evanescent field are excited,
      and a portion of their emission recouples into the fiber probe. The return path
      emission is transported by an optical fiber to a photodiode within the biosensor
      that detects and quantifies the fluorescent signal. A sandwich immunoassay was
      performed on the fiber probes with cyanine 5 dye-labeled polyclonal anti-E. coli
      O157:H7 antibodies for generation of the specific fluorescent signal. Biotin
      streptavidin interactions were used to attach polyclonal anti-E. coli O157:H7
      antibodies to the surface of the fiber probe. A centrifugation method was
      developed to obtain samples suitable for biosensor analysis from 10- and 25-g
      ground beef samples. The assay was shown to be sensitive and repeatable. One
      hundred percent correct identification of positive samples was demonstrated at
      9.0 x 10(3) CFU/g for 25-g ground beef samples with silica waveguides and at 5.2
      x 10(2) CFU/g for 10-g ground beef samples with polystyrene waveguides. The
      reaction was highly specific. No false positives were observed for 10-g ground
      beef samples not spiked with the pathogen. In addition, when samples were spiked
      with high concentrations of a variety of non-E. coli O157:H7 organisms, no false
      positives were observed. The method was rapid, with results being obtained within
      25 min of sample processing.

PMID- 11952207
TI  - Antimicrobial resistance of food-related Salmonella isolates, 1999-2000.
AB  - Salmonellosis is a major foodborne infection in the United States, and strains of
      Salmonella that are resistant to a variety of antimicrobial agents have become a
      major public health concern. To estimate the incidence of antimicrobial-resistant
      Salmonella in our food supply, the U.S. Food and Drug Administration (FDA) has
      initiated screening of foodborne isolates for sensitivity to antimicrobial
      agents, including several antibiotics. Salmonella cultures (n = 502) isolated by
      FDA laboratories during fiscal year 2000 (1 October 1999 through 30 September
      2000) from domestic and imported food products and related samples were tested
      for susceptibility to each of 12 antimicrobial agents using a disc diffusion
      assay. Because all isolates were resistant to rifampin (5 or 25 microg), only
      results with the remaining 11 antimicrobial agents are discussed in this paper.
      Of the 502 isolates, 247 (49.2%) were resistant to one or more antimicrobial
      agents, and of these 247 isolates, 170 (68.8%) were resistant to one
      antimicrobial agent, 33 (13.4%) to two antimicrobial agents, 25 (10.1%) to three
      antimicrobial agents, 7 (2.8%) to four antimicrobial agents, 8 (3.2%) to five
      antimicrobial agents, and 2 (0.8%) each to six and seven antimicrobial agents. No
      isolates were resistant to norfloxacin, whereas only seven were resistant to
      sulfamethoxazole/trimethoprim, six to trimethoprim, three to gentamicin, and one
      to ciprofloxacin. These results, for the first time, provide a baseline of data
      on the incidence of antimicrobial-resistant Salmonella in the U.S. food supply,
      which should be useful in determining the evolution of antimicrobial resistance
      in the future.

PMID- 11952208
TI  - Behavior of Escherichia coli O157:H7 during the manufacture and ripening of feta
      and telemes cheeses.
AB  - Pasteurized whole ewe's and cow's milk was used in the manufacture of Feta end
      Telemes cheeses, respectively, according to standard procedures. In both cases,
      the milk had been inoculated with Escherichia coli O157:H7 at a concentration of
      ca. 5.1 log CFU/ml and with thermophilic or mesophilic starter cultures at a
      concentration of ca. 5.3 to 5.6 log CFU/ml. In the first 10 h of cheesemaking,
      the pathogen increased by 1.18 and 0.82 log CFU/g in Feta cheese and by 1.56 and
      1.35 log CFU/ g in Telemes cheese for the trials with thermophilic and mesophilic
      starters, respectively. After 24 h of fermentation, a decrease in E. coli O157:H7
      was observed for all trials. At that time, the pH was reduced to 4.81 to 5.10 for
      all trials. Fresh cheeses were salted and held at 16 degrees C for ripening until
      the pH was reduced to 4.60. Cheeses were then moved into storage at 4 degrees C
      to complete ripening. During ripening, the E. coli O157:H7 population decreased
      significantly (P < or = 0.001) and finally was not detectable in Feta cheese
      after 44 and 36 days and in Telemes cheese after 40 and 30 days for the trials
      with thermophilic and mesophilic starters, respectively. The estimated times
      required for one decimal reduction of the population of E. coli O157:H7 after the
      first day of processing were 9.71 and 9.26 days for Feta cheese and 9.09 and 7.69
      days for Telemes cheese for the trials with thermophilic and mesophilic starters,
      respectively.

PMID- 11952209
TI  - Penetration of surface-inoculated bacteria as a result of hydrodynamic shock wave
      treatment of beef steaks.
AB  - The top surface of the raw eye of round steaks was inoculated with either green
      fluorescent protein (GFP)-labeled Escherichia coli (E. coli-GFP) or rifampin
      resistant E. coli (E. coli-rif). Cryostat sampling in concert with laser scanning
      confocal microscopy (LSCM) or plating onto antibiotic selective agar was used to
      determine if hydrodynamic shock wave (HSW) treatment resulted in the movement of
      the inoculated bacteria from the outer inoculated surface to the interior of
      intact beef steaks. HSW treatment induced the movement of both marker bacteria
      into the steaks to a maximum depth of 300 microm (0.3 mm). Because popular steak
      cooking techniques involve the application of heat from the exterior surface of
      the steak to achieve internal temperatures ranging from 55 to 82 degrees C, the
      extent of bacterial penetration observed in HSW-treated steaks does not appear to
      pose a safety hazard to consumers.

PMID- 11952210
TI  - Comparison of sampling methods for microbiological testing of beef animal
      rectal/colonal feces, hides, and carcasses.
AB  - This study compared sampling methods for detecting Escherichia coli O157:H7 and
      Salmonella in beef cattle feces and on hides and carcasses and for enumerating E.
      coli biotype I counts (ECC) on carcasses. Fecal samples were collected by
      rectal/colonal palpation and colonal sponge swabbing. Hides were sampled by
      sponge swabbing three sites, hair clipping, excision, rinsing, and gauze
      swabbing, whereas carcasses were sampled by three-site thoracic and pattern-mark
      sponge swabbing and tissue excision. Overall, irrespective of sampling method,
      36.7, 13.3, and 0.0% of lots contained at least one E. coli O157:H7-positive
      hide, fecal, and carcass sample, respectively, while the corresponding prevalence
      of Salmonella was 70.0, 16.7, and 6.7%, respectively. For hide sampling, excision
      and gauze swabbing yielded the fewest (13.3%) E. coli O157:H7-positive samples,
      while hair clipping and sponge swabbing yielded the most (23.3%). None of the
      carcass-sampling methods detected E. coli O157:H7 or differed (P > 0.05) in their
      ability to enumerate ECC. Colonal swabbing was the most effective (10.0%) method
      for detecting E. coli O157:H7 in feces. No differences (P > 0.05) in Salmonella
      prevalence were observed between carcass-sampling methods, although three-site
      sponge swabbing and tissue excision detected the most (3.3%). Hide rinsing was
      the most effective (P < 0.05) Salmonella detection method (63.3%), but dangers
      associated with its application may preclude its use by industry; there were no
      differences (P > 0.05) among other hide-sampling methods. No differences (P >
      0.05) in Salmonella detection were observed between fecal-sampling methods.
      Overall, three-site sponge swabbing was the most feasible and effective sampling
      method for the detection of E. coli O157:H7 and Salmonella on hides and
      carcasses.

PMID- 11952211
TI  - Efficacy enhancement of trisodium phosphate against spoilage and pathogenic
      bacteria in model biofilms and on adipose tissue.
AB  - A two-step approach for enhancing the efficacy of trisodium phosphate (TSP) was
      evaluated using meat spoilage and pathogenic bacteria in flow cell biofilms and
      adipose tissue model systems. The process was based on the plasmolysis of
      attached bacteria (biofilms) with a hyperosmotic solution (1.5 M NaCl) and the
      subsequent deplasmolysis of cells with a low-osmotic-strength solution containing
      different concentrations of TSP (0.1, 0.25, 0.5, 0.625, and 1.0 % [wt/vol]).
      Escherichia coli, Salmonella Enteritidis, Pseudomonas sp., Listeria
      monocytogenes, and Brochothrix thermosphacta strains were cultivated for 24 h as
      pure culture biofilms in glass flow cells with complex media and were then
      treated with either 0.1, 0.25, 0.5, 0.625, and 1.0% TSP, or the same TSP
      concentrations delivered in conjunction with plasmolysis-deplasmolysis (PDP).
      Confocal scanning laser microscopy, a commercial fluorescent viability probe, and
      image analysis were then used to quantify the relative abundances of living and
      dead cells remaining after the different treatment regimes. With the exception of
      L. monocytogenes (which was resistant to TSP concentrations of up to 5%), the PDP
      process increased the sensitivity of the test strains to TSP. However, when
      similar experiments were conducted with pork adipose tissue, it became evident
      that higher TSP concentrations were necessary to produce significant decreases in
      the number of viable cells and that the PDP process generally failed to enhance
      TSP efficacy. An exception was L. monocytogenes, which exhibited an increase in
      sensitivity to TSP when inoculated tissue was pretreated with 1.5 M NaCl. It is
      thought that factors contributing to the failure of the PDP process to enhance
      the activity of TSP in meat systems involves the mode of TSP antimicrobial
      activity, alkaline pH stress, and the chemically complex, buffered nature of
      meats. It remains to be determined whether the PDP process is suitable for use
      with other food grade antimicrobial agents or can be used in nonfood biofilm
      control applications.

PMID- 11952212
TI  - Microbiological quality and safety of ready-to-eat cooked foods from a
      centralized school kitchen in Argentina.
AB  - The purpose of this study was to evaluate the microbiological and sensory quality
      as well as the safety of ready-to-eat (RTE) cooked foods prepared in and
      distributed from a centralized kitchen to schools in Argentina. A total of 101
      cooked food samples delivered as hot RTE cooked foods (group A) and as RTE cooked
      foods at room temperature (group B) and 140 surface swab environment samples were
      collected from February to November 1999. Petrifilm plates were used for aerobic
      (PAC), coliform (PCC), and Escherichia coli (PEC) counts. Standard methods were
      used to determine Enterobacteriaceae (EntC) and thermotolerant coliform counts
      (TCC). Samples were also tested for the presence of Salmonella spp.,
      Staphylococcus aureus, Bacillus cereus, and Clostridium perfringens. Food
      temperatures just before samples were put into containers ranged from 80 to 98
      degrees C and from 28 to 32 degrees C for group A and group B, respectively. For
      group A food samples, PAC ranged from 1.04 to 3.50 log CFU/g, and PCC, PEC, TCC,
      and EntC were not detected. For group B food samples, PAC ranged from 3.63 to
      6.48 log CFU/g, PCC ranged from 1.90 to 5.36 log CFU/g, TCC ranged from 1.30 to
      3.95 log CFU/g, and EntC ranged from 3.60 to 5.46 log CFU/g. Of the foodborne
      pathogens, only B. cereus was isolated (63.4% of samples) in both food groups (<4
      log CFU/g). The microbiological and sensory quality and the safety of group A
      foods were satisfactory. Large numbers of PAC and EntC detected in group B foods
      show that better control is needed to avoid potential foodborne diseases.

PMID- 11952213
TI  - Competition of thermally injured listeria monocytogenes with a mesophilic lactic
      acid starter culture in milk for various heat treatments.
AB  - Overnight tryptose broth cultures of three L monocytogenes strains were combined,
      centrifuged, suspended in 200 ml of tryptose phosphate broth, and heated at 56
      degrees C for 20 min and at 64 degrees C for 2 min to obtain low-heat-injured
      (LHI) and high-heat-injured (HHI) cells, respectively, showing >99.6% injury.
      Flasks containing 200 ml of raw, low-heat-treated (56 degrees C for 20 min), high
      heat-treated (64 degrees C for 2 min), pasteurized, and ultrahigh-temperature
      (UHT) milk were tempered to 31.1 degrees C and inoculated to contain 10(4) to
      10(6) CFU/ml of LHI, HHI, or healthy L. monocytogenes cells and a commercial
      Lactococcus lactis subsp. lactis-Lactococcus lactis subsp. cremoris starter
      culture at levels of 0.5, 1.0, and 2.0%. Numbers of healthy and injured L.
      monocytogenes cells and starter organisms were determined using tryptose
      phosphate agar with or without 4.0% NaCl at selected intervals during 24 h of
      incubation at 31.1 degrees C. The presence of L. monocytogenes did not adversely
      affect the growth of the starter culture at any inoculation level. Overall, L.
      monocytogenes survived the 24-h fermentation period and grew to some extent. In
      starter-free controls. 76 to 81% of LHI cells and 59 to 69% of HHI cells were
      repaired after 8 h of incubation, with the lowest repair rates being observed for
      raw rather than heat-treated or pasteurized milk. Increased injury was observed
      for healthy L. monocytogenes cells at the 1.0 and 2.0% starter levels, with less
      injury seen for LHI and HHI cells. Raw and subpasteurized milk allowed less of a
      decrease in the percentage of injury and also showed higher numbers of injured
      cells than did pasteurized and UHT milks. These findings may have important
      implications for the survival of Listeria spp. in certain cheeses that can be
      prepared from raw or heat-treated milk.

PMID- 11952214
TI  - Modeling the growth of Listeria monocytogenes in cured ready-to-eat processed
      meat products by manipulation of sodium chloride, sodium diacetate, potassium
      lactate, and product moisture content.
AB  - A central composite second-order response surface design was employed to
      determine the influences of added sodium chloride (0.8 to 3.6%), sodium diacetate
      (0 to 0.2%), potassium lactate syrup (0.25 to 9.25%), and finished-product
      moisture (45.5 to 83.5%) on the predicted growth rate of Listeria monocytogenes
      in cured ready-to-eat (RTE) meat products. Increased amounts of both sodium
      diacetate (P < 0.11) and potassium lactate (P < 0.001) resulted in significant
      reductions in the growth rate constants of L monocytogenes. Increased finished
      product moisture (P < 0.11) significantly increased growth rate constants. The
      nfluence of sodium chloride was not statistically significant. The second-order
      statistical factor for lactate was significant (P < 0.01), but all two-way
      interactions were not. In general, predicted growth rates exceeded actual growth
      rates obtained from inoculation studies of four cured RTE meat products (wieners,
      smoked-cooked ham, light bologna, and cotto salami). The final model will be
      useful to food technologists in determining formulations that will result in
      finished cured RTE meat products in which L. monocytogenes is not likely to grow.

PMID- 11952215
TI  - Assessment of mathematical models for predicting Staphylococcus aureus growth in
      cooked meat products.
AB  - The growth of Staphylococcus aureus in commercially available vacuum-packaged
      cooked ham, turkey breast meat, and chicken breast meat stored at 2.3, 6.5, 10,
      13.5, and 17.7 degrees C was studied. Growth rates observed in these food
      products were compared with those predicted on the basis of various growth models
      found in the literature and with those generated by the Pathogen Modeling Program
      and the Food MicroModel software using graphical and mathematical analysis for
      performance evaluation. In general, the models studied overestimated the growth
      of S. aureus. The Dengremont and Membre model most closely matched the observed
      behavior of S. aureus in ham and chicken breast meat, with bias factors of 1.56
      and 1.09, respectively. The Eifert et al. model accurately described the growth
      of S. aureus in turkey breast meat, with a bias factor of 1.51. The remaining
      models provided safe predictions of the growth rate of S. aureus, but with poor
      accuracy. Predictive microbiology models have an immediate practical application
      in improving microbial food safety and quality and are very useful decision
      support tools, but they should not be used as the sole determinant of product
      safety.

PMID- 11952216
TI  - Taenia solium metacestode viability in infected pork after preparation with salt
      pickling or cooking methods common in Yucatan, Mexico.
AB  - The cestode parasite Taenia solium is an important cause of foodborne infection
      throughout tropical and subtropical regions. Ingestion of pork meat infected with
      T. solium larvae can lead to taeniasis infection in humans. With tourism and the
      consumption of native food increasing, it is important to investigate potential
      risks of transmission associated with food preparation methods. In this study,
      traditional Mexican salt pickling and two methods of pork preparation (as roast
      pork [cochinita pibil] and in pork and beans [frijol con puerco]) were evaluated
      in order to determine their effects on T. solium cyst viability in infected
      tissue. In the control groups, all metacestodes isolated were 100% viable, and
      only small changes in pH (from 6.0 to 5.9) and temperature (29 to 30 degrees C)
      were recorded. No viable cysts were detected after 12 and 24 h of salt pickling.
      The pH of the meat during salting dropped from 6.0 to 5.3. Osmotic changes and
      dehydration from the salting, rather than a change in pH, could be considered the
      main cause of cyst death. Temperatures of >65 degrees C damaged T. solium
      metacestodes in roast pork and in pork and beans. The results of this study
      indicate that if traditional pork dishes are prepared properly, T. solium cysts
      are destroyed. The criteria used in this study to evaluate the viability of
      tissue cysts are discussed.

PMID- 11952217
TI  - Misidentification of Vibrio cholerae O155 isolated from imported shrimp as O
      serogroup O139 due to cross-agglutination with commercial O139 antisera.
AB  - Fish and shellfish products imported into Denmark are routinely analyzed for
      pathogenic Vibrio spp., particularly Vibrio cholerae, if products originate from
      subtropical or tropical areas. A V. cholerae strain that agglutinated commercial
      O139 antiserum but not the O1, Inaba, or Ogawa antisera was isolated from
      imported raw frozen shrimp. The toxigenicity of the strain was analyzed, and the
      results of a polymerase chain reaction showed that the V. cholerae strain did not
      contain the virulence genes ctx, tcpA, and zot, which are normally found in V.
      cholerae O1 and O139. The strain was resistant to colistin and spectinomycin. The
      high susceptibility of the strain to antimicrobial agents was confirmed by the
      lack of an SXT element, a self-transmissible, chromosomal genetic element that is
      normally present in 0139 strains and encodes resistance to sulfonamides,
      trimethoprim, and streptomycin. The strain contained two plasmids, in contrast to
      other O139 strains, which normally do not contain plasmids. The characteristics
      of the strain led to further agglutination testing with other antisera that are
      not commercially available, and the strain was found to agglutinate O155
      antiserum in repeated testing. Manufacturers of 0139 antiserum should be aware of
      the closely related O antigens of the O139, O22, and O155 serogroups and should
      be aware that their commercial diagnostic O139 antiserum must be absorbed to
      remove cross-reacting agglutinins of O22 and O155 strains.

PMID- 11952218
TI  - Effect of irrigation method on transmission to and persistence of Escherichia
      coli O157:H7 on lettuce.
AB  - In this study, the transmission of Escherichia coli O157:H7 to lettuce plants
      through spray and surface irrigation was demonstrated. For all treatments
      combined, the number of plants testing positive following a single exposure to E.
      coli O157: H7 through spray irrigation (29 of 32 plants) was larger than the
      number testing positive following surface irrigation (6 of 32 plants). E. coli
      O157:H7 persisted on 9 of 11 plants for 20 days following spray irrigation with
      contaminated water. Immersion of harvested lettuce heads for 1 min in a 200 ppm
      chlorine solution did not eliminate all E. coli O157:H7 cells. The results of
      this study suggest that regardless of the irrigation method used, crops can
      become contaminated; therefore, the irrigation of food crops with water of
      unknown microbial quality should be avoided.

PMID- 11952219
TI  - Microbial evaluation of selected fresh produce obtained at retail markets.
AB  - The microbial quality of five types of fresh produce obtained at the retail level
      was determined by standard quantitative techniques. These techniques included
      aerobic plate count (APC), total coliform counts, Escherichia coli counts, and
      yeast and mold counts. Three different methods were used to determine total
      coliform counts, which consisted of MacConkey agar plate counts, Colicomplete
      most probable number counts, and Petrifilm E. coli (EC) plate counts. The mean
      APCs for sprouts, lettuce, celery, cauliflower, and broccoli were 8.7, 8.6, 7.5,
      7.4. and 6.3 log10 CFU/g, respectively. MacConkey agar counts indicated that 89
      to 96% of the APCs consisted of gram-negative bacteria. Yeast and mold counts
      were in a range expected of fresh produce. Fresh produce was also analyzed for
      human pathogens. Samples were analyzed for Staphylococcus spp., Bacillus spp.,
      Salmonella spp., Listeria spp., and Campylobacter spp. One isolate of
      Staphylococcus was found to be enterotoxigenic, and one species of Bacillus was
      also toxigenic. Neither Salmonella spp. nor Campylobacter spp. were detected in
      any of the produce samples. A variety of Listeria spp., including Listeria
      monocytogenes, were found in fresh produce.

PMID- 11952220
TI  - Spice oils for the control of co-occurring mycotoxin-producing fungi.
AB  - The effect of nine different oils was evaluated on the growth of Aspergillus
      parasiticus and Fusarium moniliforme. The experimental design to examine the
      inhibition of mycotoxins involved the incorporation of each of seven oils into
      broth and patty cultures. The fungal mycotoxin was identified by high-pressure
      liquid chromatography. Clove oil (eugenol) was the most inhibitory to the growth
      of A. parasiticus and F. moniliforme, followed by cinnamon (cinnamic aldehyde),
      oregano (thymol and carvacol) and mace oils (myristin). Neem and eucalyptus oil
      (cineole) did not affect fungal growth. The feasibility of implementing the
      results of this study to control mycotoxin toxicity was examined by costoring
      whole and ground cloves with mycotoxin-infected grain. Addition of both whole and
      ground cloves markedly reduced the aflatoxin contamination of the grain. These
      results clearly suggest that commonly occurring mycotoxigenic fungi can be
      controlled with clove oil (eugenol), thus spice oil successfully inhibited the
      growth of A. parasiticus and F. moniliforme, regulated the production of
      fumonisins. and prevented the formation of aflatoxins. The social implication of
      this finding is that rural communities can prevent the formation of fungal toxins
      in contaminated grain by simple measures.

PMID- 11952221
TI  - Development of a method for the determination of pyrimethamine concentrations in
      feeds by ion-pairing high-performance liquid chromatography.
AB  - An ion-pairing reversed-phase high-performance liquid chromatography (HPLC)
      method with diode array detection at 280 nm was developed to determine
      pyrimethamine concentrations in feed for laying hens. Pyrimethamine was extracted
      with a mixture of 5% isobutanol and 95% benzene, and the extract was cleaned up
      on an alumina column. The drug was eluted from an Intersil ODS-3V column (250 by
      4.6 mm) with a mixture of 25% acetonitrile and 75% water (vol/vol) containing
      0.01 M tetramethylammonium chloride as an ion-pairing agent and adjusted with
      acetic acid to pH 3.5. The flow rate was 1.0 ml/min. Mean recovery of
      pyrimethamine from supplemented feeds at concentrations of 2, 4, and 5 microg/g
      of feed were 100.5, 103.5, and 100.8%, respectively. Precision within a day
      ranged from 4.3 to 7.0% for the three concentrations, and day-to-day precision
      was 5.3% for feed supplemented at a concentration of 4 microg/g. No
      chromatographic interference was detected from other 2,4-diaminopyrimidine
      compounds or other major drugs used in poultry.

PMID- 11952222
TI  - Polymerase chain reaction-restriction fragment length polymorphism analysis of a
      16S rRNA gene fragment for authentication of four clam species.
AB  - Specific identification of four clam species, Ruditapes decussatus (grooved
      carpet shell), Venerupis pullastra (pullet carpet shell), Ruditapes philippinarum
      (Japanese carpet shell), and Venerupis rhomboides (yellow carpet shell), was
      achieved by polymerase chain reaction-restriction fragment length polymorphism
      analysis of a fragment of the mitochondrial 16S rRNA gene. Amplification of DNA
      isolated from the foot muscle produced fragments of 511 bp for V. pullastra, 523
      bp for R. decussatus, 545 bp for R. philippinarum, and 502 bp for V. rhomboides.
      The restriction profiles obtained by agarose gel electrophoresis when amplicons
      were digested with endonucleases BsmAI and BsrI allowed unequivocal
      identification of the four clam species. This approach would be less costly,
      simpler, and quicker than conventional sequencing of polymerase chain reaction
      products followed by detailed comparison of individual sequences, especially when
      large numbers of samples need to be analyzed.

PMID- 11952223
TI  - Campylobacter jejuni infection during pregnancy: long-term consequences of
      associated bacteremia, Guillain-Barre syndrome, and reactive arthritist.
AB  - Campylobacter jejuni infections are the main cause of foodborne gastroenteritis
      in the United States and other developed countries. Generally, C. jejuni
      infections are self-limiting and treatment is not necessary; however, infections
      caused by this organism can lead to potentially dangerous long-term consequences
      for some individuals. Bacteremia, Guillain-Barre syndrome (GBS; an acute flaccid
      paralytic disease), and reactive arthritis (ReA) are the most serious of the long
      term consequences of C. jejuni infections. During pregnancy, foodborne infections
      may be hazardous to both the woman and the fetus. C. jejuni-induced bacteremia
      during pregnancy may lead to intrauterine infection of the fetus, abortion,
      stillbirth, or early neonatal death. Infection of a newborn by the mother during
      the birth process or shortly after birth may lead to neonatal enteritis,
      bacteremia, and/or meningitis. C. jejuni enteritis is the inducing antecedent
      infection in approximately 30% of cases of GBS. Thus, pregnant women infected
      with C. jejuni may contract GBS. GBS during pregnancy does not affect fetal or
      infant development and does not increase spontaneous abortion or fetal death;
      however, it may induce spontaneous delivery during the third trimester in severe
      cases. Reactive arthritis occurs in approximately 2% of C. jejuni enteritis cases
      and leads to the impaired movement of various joints. Pregnant women with C.
      jejuni-induced reactive arthritis can be expected to deliver a normal infant. A
      pregnant patient with GBS or ReA may be unable to care for a newborn infant
      because of the physical impairment induced by these diseases. Since C. jejuni
      infections put both fetuses and pregnant women at risk, pregnant women must take
      special care in food handling and preparation to prevent such infections.

PMID- 11952224
TI  - Control of Listeria monocytogenes in the food-processing environment.
AB  - The purpose of this paper is to provide guidance to food processors in
      controlling Listeria monocytogenes in food-processing environments. Of particular
      concern are outbreaks of a few to several hundred scattered cases involving an
      unusually virulent strain that has become established in the food-processing
      environment and contaminates multiple lots of food over days or months of
      production. The risk is highest when growth occurs in a food before it is eaten
      by a susceptible population. The information presented in this paper provides the
      basis for the establishment of an environmental sampling program, the
      organization and interpretation of the data generated by this program, and the
      response to Listeria-positive results. Results from such a program, including
      examples of niches, are provided. Technologies and regulatory policies that can
      further enhance the safety of ready-to-eat foods are discussed.

PMID- 11952225
TI  - Protein-water interactions.
AB  - By recognizing the forces that drive water transport across cell membranes or
      across tissues, we can see how water is driven to and from proteins. We learn
      from examples. When a dissolved protein (bovine serum albumin) accumulates water
      relative to small solutes, it effectively withdraws a number of water molecules
      from the bath; the number of water molecules changes with the identity but not
      with the concentration of small solutes. When a large ionic channel (VDAC or
      alamethicin) opens, it withdraws water from its bathing solution; excluded solute
      stabilizes the closed state in proportion to activity of water, the osmotic
      stress created by the solute, rather than in proportion to the activity of the
      solute itself. Hemoglobin too acts like an osmometer whose loading of oxygen
      shifts with the chemical potential of water. Assemblies of many macromolecules
      (proteins, nucleic acids, polysaccharides, lipids), subjected to the osmotic
      stress of completely excluded solutes, fight dehydration with powerful,
      exponentially varying intermolecular forces. Should we speak of these
      sensitivities and responses as solute effects or water effects? Intuitive but
      rigorous thermodynamics, developed in a set of appendixes, provides a
      surprisingly practical guide to alternatives in language.

PMID- 11952226
TI  - Molecular physiology of aquaporins in plants.
AB  - In plants, membrane channels of the major intrinsic protein (MIP) super-family
      exhibit a high diversity with, for instance, 35 homologues in the model species
      Arabidopsis thaliana. As has been found in other organisms, plant MIPs function
      as membrane channels permeable to water (aquaporins) and in some cases to small
      nonelectrolytes. The aim of the present article is to integrate into plant
      physiology what has been recently learned about the molecular and functional
      properties of aquaporins in plants. Exhaustive compilation of data in the
      literature shows that the numerous aquaporin isoforms of plants have specific
      expression patterns throughout plant development and in response to environmental
      stimuli. The diversity of aquaporin homologues in plants can also be explained in
      part by their presence in multiple subcellular compartments. In recent years,
      there have been numerous reports that describe the activity of water channels in
      purified membrane vesicles, in isolated organelles or protoplasts, and in intact
      plant cells or even tissues. Altogether, these data suggest that the transport of
      water and solutes across plant membranes concerns many facets of plant
      physiology. Because of the high degree of compartmentation of plant cells,
      aquaporins may play a critical role in cell osmoregulation. Water uptake in roots
      represents a typical process in which to investigate the role of aquaporins in
      transcellular water transport, and the mechanisms and regulations involved are
      discussed.

PMID- 11952227
TI  - Osmotic adaptation in yeast--control of the yeast osmolyte system.
AB  - The yeast Saccharomyces cerevisiae (baker's yeast or budding yeast) is an
      excellent eukaryotic model system for cellular biology with a well-explored,
      completely sequenced genome. Yeast cells possess robust systems for osmotic
      adaptation. Central to the response to high osmolarity is the HOG pathway, one of
      the best-explored MAP kinase pathways. This pathway controls via different
      transcription factors the expression of more than 150 genes. In addition, osmotic
      responses are also controlled by protein kinase A via a general stress response
      pathway and by presently unknown signaling systems. The HOG pathway partially
      controls expression of genes encoding enzymes in glycerol production. Glycerol is
      the main yeast osmolyte, and its production is essential for growth in a high
      osmolarity medium. Upon hypo-osmotic shock, yeast cells transiently stimulate
      another MAP kinase pathway, the so-called PKC pathway, which appears to
      orchestrate the assembly of the cell surface and the cell wall. In addition,
      yeast cells show signs of a regulated volume decrease by rapidly exporting
      glycerol through Fps1p. This unusual MIP channel is gated by osmotic changes and
      thereby plays a key role in controlling the intracellular osmolyte content. Yeast
      cells also possess two aquaporins, Aqy1p and Aqy2p. The production of both
      proteins is strictly regulated, suggesting that these water channels play very
      specific roles in yeast physiology. Aqy1p appears to be developmentally
      regulated. Given the strong yeast research community and the excellent tools of
      genetics and functional genomics available, we expect yeast to be the best
      explored cellular organism for several years ahead, and osmotic responses are a
      focus of interest for numerous yeast researchers.

PMID- 11952228
TI  - Adaptation of kidney medulla to hypertonicity: role of the transcription factor
      TonEBP.
AB  - The osmolality of the mammalian kidney medulla is very high. The high osmolality
      provides the driving force for water reabsorption and urinary concentration, key
      functions of the kidney for maintaining proper body fluid volume and blood
      pressure. Salt and urea are the major solutes in the renal medullary
      interstitium. Unfortunately, high salt (hypertonicity) causes DNA damage and cell
      death. In response, the renal medullary cells adapt to the hypertonicity by
      accumulating compatible osmolytes. A regulatory protein, tonicity-responsive
      enhancer binding protein (TonEBP), plays a central role in the accumulation of
      these compatible osmolytes by stimulating genes whose products either actively
      transport or synthesize the appropriate osmolytes. TonEBP is active under
      isotonic conditions. It responds to both an increase and a decrease in ambient
      tonicity, in opposite directions, which involves changes in its abundance and
      nucleocytoplasmic distribution. In the kidney medulla, however, nucleocytoplasmic
      distribution is the major site of control, under normal conditions of diuresis
      and antidiuresis.

PMID- 11952229
TI  - Passive water transport in biological pores.
AB  - Three kinds of membrane proteins have been shown to have water channels
      properties: the aquaporins, the cotransporters, and the uniports. A molecular
      kinetic description of water transport in pores is compared to analytical models
      based on macroscopic parameters such as pore diameter and length. The use and
      limitations of irreversible thermodynamics is discussed. Experimental data on
      water and solute permeability in aquaporins are reviewed. No unifying transport
      model based on macroscopic parameters can be set up; for example, there is no
      correlation between solute diameter and permeability. Instead, the influence of
      hydrogen bonds between solute and pore, and the pH dependence of permeability,
      point toward a model based upon chemical interactions. The atomic model for AQP1
      based on electron crystallographic data defines the dimensions and chemical
      nature of the aqueous pore. These structural data combined with quantum
      mechanical modeling and computer simulation might result in a realistic
      description of water transport. Data on water and solute permeability in
      cotransporters and uniports are reviewed. The function of these proteins as
      substrate transporters involves a series of conformational changes. The role of
      conformational equilibria on the water permeability will be discussed.

PMID- 11952230
TI  - Cell volume homeostasis: ionic and nonionic mechanisms. The sodium pump in the
      emergence of animal cells.
AB  - Plant cells and bacterial cells are surrounded by a massive polysaccharide wall,
      which constrains their high internal osmotic pressure (tens of atmospheres).
      Animal cells, in contrast, are in osmotic equilibrium with their environment,
      have no restraining surround, and can take on a variety of shapes and can change
      these from moment to moment. This osmotic balance is achieved, in the first
      place, by the action of the energy-consuming sodium pump, one of the P-type
      ATPase transport protein family, members of which are found also in bacteria. The
      pump's action brings about a transmembranal electrochemical gradient of sodium
      ions, harnessed in a range of transport systems which couple the dissipation of
      this gradient to establishing a gradient of the coupled substrate. These
      transport systems include many which are responsible for short-term regulation of
      the cell's volume in response to acute changes of their osmotic balance. Thus,
      the primary role of the sodium pump as a regulator of cell volume has been built
      upon to provide the basis for an enormous variety of physiological functions.

PMID- 11952231
TI  - Cotransporters as molecular water pumps.
AB  - Molecular water pumps are membrane proteins of the cotransport type in which a
      flux of water is coupled to substrate fluxes by a mechanism within the protein.
      Free energy can be exchanged between the fluxes. Accordingly, the flux of water
      may be relatively independent of the external water chemical potential and can
      even proceed uphill. In short, water is being cotransported. The evidence for
      water cotransport is reviewed with particular emphasis on electrogenic
      cotransporters expressed in Xenopus oocytes under voltage clamped conditions.
      Phenomena such as uphill water transport, tight coupling between water transport
      and clamp current, cotransport of small hydrophilic molecules, and shifts in
      reversal potentials with osmolarity are discussed with examples from the
      Na+/glutamate and Na+/glucose cotransporters. Unstirred layers and electrode
      artifacts as alternative explanations for such cotransport can be ruled out for
      both experimental and theoretical reasons. Indeed, substrate fluxes mediated by
      channels or ionophores generate much smaller water fluxes than those observed
      with cotransporters. Theoretical models, using reasonable values for the
      intracellular diffusion coefficient, indicate the presence of only small
      unstirred layers in the membranes studied.

PMID- 11952232
TI  - General models for water transport across leaky epithelia.
AB  - The group of leaky epithelia, such as proximal tubule and small intestine, have
      several common properties in regard to salt and water transport. The fluid
      transport is isotonic, the transport rate increases in dilute solutions, and
      water can be transported uphill. Yet, it is difficult to find common features
      that could form the basis for a general transport model. The direction of
      transepithelial water transport does not correlate with the direction of the
      primary active Na+ transport, or with the ultrastucture as defined by the
      location of apical and basolateral membranes, of the junctional complex and the
      lateral intercellular spaces. The presence of specific water channels,
      aquaporins, increases the water permeability of the epithelial cell membranes,
      i.e., the kidney proximal tubule. Yet other leaky epithelia, for example, the
      retinal pigment epithelium, have no known aquaporins. There is, however, a
      general correlation between the direction of transepithelial transport and the
      direction of transport via cotransporters of the symport type. A simple
      epithelial model based on water permeabilities, a hyperosmolar compartment and
      restricted salt diffusion, is unable to explain epithelial transport phenomena,
      in particular the ability for uphill water transport. The inclusion of
      cotransporters as molecular water pumps in these models alleviates this problem.

PMID- 11952233
TI  - Paracellular fluid transport by epithelia.
AB  - The evidence that a major fraction of water crosses the paracellular route during
      isotonic fluid transfer is reviewed together with a description of the theory and
      experimental results derived from extracellular probe studies. Four transporting
      epithelia which have been studied using the method are gallbladder, intestine,
      Malpighian tubule, and salivary gland. It is concluded that paracellular probe
      flows are not due to simple convection generated by osmotic flow through the
      junctions but are generated by active fluid transport within the junction: a
      mechano-osmotic process. The geometry of the pathway involved would indicate that
      some salt accompanies the paracellular fluid, representing a hypo-osmotic flow.
      Transport of salt by the cell route, which may be accompanied by some water,
      represents a hypertonic flow. The problem then becomes one of balancing the two
      to produce an isotonic transportate. We suggest, using recent data from knockout
      mice, that some aquaporins are functioning in different epithelial tissues as
      osmo-comparators within a feedback loop that regulates the paracellular fluid
      flow rate. This results in an overall quasi-isotonic transport by the epithelium.
      The model is applied to forward-facing systems such as proximal tubule and
      backward-facing systems such as exocrine glands.

PMID- 11952234
TI  - The lipid-water interface: revelations by osmotic stress.
AB  - Lipids at the bilayer-water interface are highly disordered and mobile, and large
      areas of the bilayer undergo thermal undulations. Water penetrates significantly
      down to the hydrocarbon chain level. This water, and water out to about 10 A from
      the surface, is perturbed by the lipid surface in a way that produces a strong
      hydration repulsion and precludes molecular contact between bilayers. Its removal
      costs work, but most of this water is neither a permeable barrier nor unavailable
      to solvate other solutes. All hydrophilic surfaces show this "hydration force."
      Most lipids have an excess higher free energy when packed within a bilayer
      membrane since in isolation they pack into high curvature assemblies with polar
      groups on the concave side. Osmotic stress measurements of those curved
      assemblies yield a measure of monolayer elastic parameters and the excess higher
      free energy, which likely controls embedded proteins. Osmotic stress experiments
      can determine whether water is energetically significant, or not, in almost any
      system. The osmotic effect of solutes, independent of specific binding, is to
      compete with lipids and proteins for water. Solute affinity for water can modify
      lipid packing and protein conformation, coupling lipid and protein structure and
      function to osmolality at the molecular level.

PMID- 11952235
TI  - Osmoregulation and contractile vacuoles of protozoa.
AB  - Protozoa living in fresh water are subjected to a hypotonic environment. Water
      flows across their plasma membrane since their cytosol is always hypertonic to
      the environment. Many wall-less protozoa have an organelle, the contractile
      vacuole complex (CVC), that collects and expels excess water. Recent progress
      shows that most, if not all, CVCs are composed of a two-compartment system
      encircled by two differentiated membranes. One membrane, which is often divided
      into numerous vesicles and tubules, contains many proton-translocating V-ATPase
      enzymes that provide an electrochemical gradient of protons and which fuses only
      with the membrane of the second compartment. The membrane of the second
      compartment lacks V-ATPase holoenzymes, expands into a reservoir for fluid
      storage, and is capable of fusing with the plasma membrane. It is this second
      compartment that periodically undergoes rounding ("contraction"), setting the
      stage for fluid expulsion. Rounding is accompanied by increased membrane tension.
      We review the current state of knowledge on osmolarity, ion concentrations,
      membrane permeability, and electrophysiological parameters of cells and their
      contractile vacuoles, where these criteria are helpful to our understanding of
      the function of the CVC. Effects of environmental stresses on the CVC function
      are also summarized. Finally, other functions suggested for CVCs based on
      molecular and physiological studies are reviewed.

PMID- 11952236
TI  - Molecular mechanisms of water transport in the eye.
AB  - The four major sites for ocular water transport, the corneal epithelium and
      endothelium, the ciliary epithelium, and the retinal pigment epithelium, are
      reviewed. The cornea has an inherent tendency to swell, which is counteracted by
      its two surface cell layers, the corneal epithelium and endothelium. The
      bilayered ciliary epithelium secretes the aqueous humor into the posterior
      chamber, and the retinal pigment epithelium transports water from the retinal to
      the choroidal site. For each epithelium, ion transport mechanisms are associated
      with fluid transport, but the exact molecular coupling sites between ion and
      water transport remain undefined. In the retinal pigment epithelium, a H+-lactate
      cotransporter transports water. This protein could be the site of coupling
      between salt and water in this epithelium. The distribution of aquaporins does
      not suggest a role for these proteins in a general model for water transport in
      ocular epithelia. Some water-transporting membranes contain aquaporins, others do
      not. The ultrastructure is also variable among the cell layers and cannot be
      fitted into a general model. On the other hand, the direction of cotransport in
      symporters complies with the direction of fluid transport in both the corneal epi
      and endothelium, as well as the ciliary epithelium and retinal pigment
      epithelium.

PMID- 11952237
TI  - Water as it applies to the function of enzymes.
AB  - Escherichia coli and Saccharomyces cerevisiae can metabolize, grow, and divide
      over osmotic pressures ranging from 0.24 atm to about 100 atm [Record, T. M. et
      al. (1999). Trends Biochem. Sci. 23,143-148,190-194; Wood, J. M. (1999).
      Microbiol. Mol. Bio. Rev. 63, 230-262; Marachal, P. A., and Gervais, P. (1994).
      Appl. Microbiol. Biotechnol. 42, 617-622]. At the higher end of the range, they
      perform their functions with difficulty, but they can survive. Over the full span
      of pressures, the activity of water goes from 0.9998 to 0.93. Neither of the
      authors can survive at anything like these extremes; some of their enzymes and
      enzymatic complexes would "fall apart," would either cease to function or would
      denature. We would very much like to know just how the two microbes manage.

PMID- 11952238
TI  - Aquaglyceroporins: channel proteins with a conserved core, multiple functions,
      and variable surfaces.
AB  - Membrane channels for water and small nonionic solutes are required for
      osmoregulation in bacteria, plants, and animals. Aquaporin-1, the water channel
      of human erythrocytes, is the first channel demonstrated to conduct water, by
      expression in Xenopus oocytes. Phylogenetic analyses reveal the existence of two
      clusters of subfamilies, the aquaporins (AQPs) and glycerol facilitators (GLPs).
      Sequence-based structure prediction provided a model comprising six membrane
      spanning helices, while sequence analyses suggested strategic residues that are
      important for structure and function. The surface topography of several AQPs has
      been mapped by atomic force microscopy, revealing different features that
      correlate with differences in the loops connecting transmembrane helices. The 3D
      structures of AQP1 and GlpF have been determined by electron cryomicroscopy. The
      3.8-A density map allowed the first atomic model of AQP1 to be built, taking into
      account data from sequence analyses. This model provides some insight into the
      permeation of water through a channel that blocks the passage of protons. GIpF
      has been resolved to 6.9 A, revealing helices that are similar to those of AQP1.
      Homology modeling shows the channel region of these distant aquaglyceroporins to
      be similar, as confirmed by the 2.2-A structure of GlpF from X-ray
      crystallography.

PMID- 11952239
TI  - Emergency thoracotomy: appropriate use in the resuscitation of trauma patients.
AB  - The objective of this study was to evaluate the use of emergency thoracotomy in
      our institution in an effort to determine whether this procedure is both
      beneficial and cost effective in blunt and/or penetrating trauma. We conducted a
      retrospective review of charts and coroner's reports. Our setting was a Level I
      trauma center in a tertiary-care facility. We examined the cases of trauma
      patients presenting to the trauma center over a 2-year period. Of 2490 patients
      who presented to the emergency department over the study period 41 underwent
      early thoracotomy. Twelve of these were excluded from the study because their
      cases were not truly emergent. Of the remaining 29 ten were admitted for
      penetrating injuries and 19 for blunt injuries. The average Injury Severity
      Scores for penetrating and blunt injuries were 30 and 40 respectively. There were
      four blunt trauma patients who died in the emergency department, 15 went to the
      operating room, and five who survived to go to the intensive care unit. All blunt
      trauma patients requiring emergency thoracotomy died within 9 days of
      presentation. Of the ten penetrating wound patients two died in the emergency
      department, four died in the operating room, and four went to the intensive care
      unit after surgery. One of the four patients who went to the intensive care unit
      died approximately 6 days after injury. The other three patients survived and are
      now living normal productive lives. All survivors of penetrating trauma who
      required emergency thoracotomy had their procedure performed in the operating
      room. Overall survival rates for penetrating and blunt trauma were 30 and 0 per
      cent respectively. Pericardial tamponade was found in 50 per cent of the
      penetrating trauma patients (two of the three survivors) and four of 19 of the
      blunt trauma patients. This reinforces the importance of a prompt pericardiotomy
      upon opening the chest. At our institution the algorithm for emergency
      thoracotomy is liberal and is not cost effective for blunt trauma. We need to re
      evaluate our decision-making process concerning the use of emergency thoracotomy
      especially in the blunt trauma patient. The review also shows the importance of
      pericardiotomy when performing an emergency thoracotomy.

PMID- 11952240
TI  - Urban trauma centers: not quite dead yet.
AB  - With decreasing violent crime and an increase in the use of nonoperative
      management techniques the viability of urban trauma centers has come into
      question. In addition the workload and productivity for surgeons at such centers
      may be threatened. The current study examines the changing characteristics of
      patients admitted to an urban Level I trauma center over a 5-year period and
      examines factors that may affect trauma surgeon utilization. We reviewed all
      trauma registry admissions from January 1995 through December 1999. Data were
      collected regarding patient demographics, mechanism of injury, diagnostic workup,
      injury character and severity, operative procedures, intensive care unit (ICU)
      length of stay (LOS), hospital LOS, and patient disposition. Admissions declined
      23 per cent over the 5-year period. Fewer patients were admitted to general
      practice units whereas more patients required ICU admission. Over the study
      period both mean patient age and mean Injury Severity Score increased
      significantly. Gunshot wound admissions declined by 45 per cent, but the
      percentage of those admitted who required operation rose 17 per cent. Number of
      operations for trauma performed by general surgeons was unchanged over time.
      Hospital LOS declined over time, and ICU LOS was unchanged. Although trauma
      center admissions--particularly those due to violent crime--are on the decline
      the operative productivity of trauma surgeons has remained unchanged. Patients
      admitted to the hospital are older and more severely injured; they undeniably
      require a higher level of care and service coordination. Urban trauma centers
      remain viable and are in fact more efficient in caring for sicker patients.

PMID- 11952241
TI  - Indicators for tracheostomy in patients with traumatic brain injury.
AB  - Our objective was to develop criteria to identify patients with traumatic brain
      injury (TBI) who require a tracheostomy (TR). From January 1994 to May 2000 all
      TBI patients requiring intubation on presentation and who survived >7 days were
      identified from our trauma registry. Demographics, Glasgow Coma Score (GCS),
      Injury Severity Score (ISS), and ventilator days, ICU days, hospital days, need
      for TR, and development of pneumonia were statistically analyzed. Of 246 patients
      with TBI 211 without TR and 35 with TR were identified (mean time to TR 13.3+/
      7.0 days). Logistic regression analysis identified presenting GCS < or =8, ISS >
      or =25, and ventilator days >7 as significant predictors for TR. Applying these
      three predictors to our population identified 48 patients (21 with TR, 18 without
      TR, and nine who died on the ventilator without TR) with a sensitivity of 60 per
      cent, a specificity of 87 per cent, a positive predictive value of 44 per cent,
      and a negative predictive value of 93 per cent. Patients with TR had lower
      presenting GCS and higher ventilator, ICU, and hospital days (P < 0.05).
      Pneumonia rates were similar. Time to neurologic recovery (GCS > or =9) was
      longer for the TR patients as compared with the patients without TR. We conclude
      that patients with TBI presenting with a GCS < or =8, an ISS > or =25, and
      ventilator days >7 are more likely to require TR. Performing TR late did not
      reduce pneumonia rates or ventilator, ICU, or hospital days. By identifying the
      at-risk population early TR could be performed in an attempt to decrease
      morbidity and length of stay.

PMID- 11952242
TI  - Preoperative chemoradiation in the management of adenocarcinoma of the body of
      the pancreas.
AB  - Adenocarcinoma of the body of the pancreas has been traditionally associated with
      low resectability and poor prognosis. We reviewed 30 consecutive cases of
      pancreatic body adenocarcinoma presenting between 1988 and 2001. Twenty-six (87%)
      patients received preoperative chemotherapy (either 5-fluorouracil with or
      without mitomycin C or gemcitabine) plus radiation therapy (50.4 Gy), and four
      patients received chemoradiation postoperatively. During or shortly after
      chemoradiation 16 (53%) patients developed distant metastasis (n = 12), tumor
      progression (n = 2), or fatal septic complications (n = 2). Fourteen patients
      underwent surgical resection with curative intent. Resections performed included
      distal subtotal pancreatectomies (n = 6), extended pancreaticoduodenectomies (n =
      6), and total pancreatectomies (n = 2). Ten patients (71%) required vascular
      reconstruction as a result of involvement of the portal vein or the superior
      mesenteric, hepatic arterial, or celiac vessels. Median overall survival was 34
      months (range 8-152) for the resected group as compared with 8 months (range 1
      14) in the unresected group (P = 0.005). Five-year actuarial overall survival is
      projected at 45 per cent for the resected group. In this poor-prognostic subset
      of patients with pancreatic cancer preoperative chemoradiation followed by an
      aggressive surgical approach was associated with resectability and long-term
      survival of a significant minority of patients.

PMID- 11952243
TI  - Pancreatic resection for locally advanced primary and metastatic nonpancreatic
      neoplasms.
AB  - We conducted a retrospective review of our single-institution experience with
      pancreas resection for locally advanced primary malignancy or metastases from
      other organs. From January 1989 through April 2001 35 patients underwent
      pancreatic resection for locally advanced primary (17) and recurrent
      nonpancreatic (18) tumors. Patient records were examined for recurrence and
      survival. Seventeen patients with locally advanced primary tumors presented with
      pancreatic extension either into the head/body (six) or tail (11). Pancreatic
      resections were completed as en bloc procedures with the primary disease of
      stomach (five), colon (four), sarcoma (five), adrenal gland (one), or spleen
      (one). Procedures performed included pancreaticoduodenectomy for proximal lesions
      and distal pancreatectomy for disease limited to the pancreatic tail. Median
      overall survival was 56 months. Fourteen of 17 patients remain alive: three with
      disease and 11 without evidence of recurrence. Eighteen patients presented with
      recurrent tumor from a previously resected right upper quadrant tumor (nine) or
      metastases from an intra-abdominal source (nine). The primary source was colon
      (eight), biliary (three), sarcoma (three), melanoma (two), ovary (one), and
      unknown primary (one). Patients underwent pancreaticoduodenectomy, distal
      pancreatectomy, or resection of residual pancreas. Overall median survival was 46
      months. In this group of 18 patients there was no increased survival in those
      patients with a time to recurrence from their primary tumor resection greater
      than 2 years. We conclude that pancreatic resection for locally advanced
      nonpancreatic or recurrent intra-abdominal malignancies is possible in properly
      selected patients. The ability to obtain disease-free margins through en bloc
      resection is a key component of therapy.

PMID- 11952244
TI  - Early and late outcome of bedside percutaneous tracheostomy in the intensive care
      unit.
AB  - To simplify long-term airway management in critically ill patients the
      feasibility of performing percutaneous tracheostomy (PT) in the intensive care
      unit (ICU) was investigated from August of 1997 to March of 2000. Bedside PT was
      considered for patients with positive end-expiratory pressure <10 cm H20, no
      previous tracheostomy, no anatomic distortion of the tracheal region, and no
      other indication to go to the operating room. Indication for tracheostomy,
      duration of endotracheal intubation, Acute Physiology and Chronic Health
      Evaluation II (APACHE II) score, morbidity, and mortality were determined.
      Patients were prospectively followed until decannulation or for a minimum of 3
      months. PT was performed in the ICU in 71 patients. Indications for PT were:
      acute respiratory failure (41), airway protection (26), and maxillofacial trauma
      (four). Mean duration of intubation before PT was 14 days (range 5-35 days).
      Average APACHE II score was 14 (range 3-28). Morbidity from PT included: early
      (two) and late (one) bleeding from the tracheostomy, early cuff leak (one), and
      self-decannulation (one). Sixteen patients died of causes unrelated to PT. Forty
      five patients were decannulated after an average of 57 days (range 9-170 days);
      two noted a minor voice change. PT can be performed in the ICU with minimal
      morbidity eliminating the need for an operating room, the risks of patient
      transport, and the costs associated with each.

PMID- 11952245
TI  - Should esophagectomy be performed in a low-volume center?
AB  - A significant difference has been reported between rates of morbidity and
      mortality for elective esophagectomy performed at low-volume centers versus high
      volume centers. Some authors have suggested that complex surgical procedures such
      as esophagectomy should be performed only in regional centers by surgeons with an
      extensive procedure-specific experience. This study was performed to review
      recent (5 years) experience with esophagectomy in two university-affiliated
      hospitals where a limited number of esophageal resections are performed annually.
      Esophageal resections performed between February 1995 and February 2000 at two
      university-affiliated tertiary-care hospitals were analyzed for operative
      morbidity and mortality. Variables reviewed included demographics, surgeon
      experience, mortality, and complications. Forty-three patients underwent elective
      esophagectomy during the 5-year study period. In-hospital mortality was 7.0 per
      cent and 30-day mortality was 4.7 per cent. The anastomotic leak rate was 11.6
      per cent. No patients developed myocardial infarction or renal failure. Morbidity
      and mortality rates from our low-volume centers compared favorably with high
      volume centers. We conclude that elective esophagectomy can be safely performed
      at low-volume centers with favorable morbidity and mortality rates.
      Recommendations urging regionalization of high-risk procedures should be guided
      by local outcomes and not by the total number of procedures performed at a
      specific center.

PMID- 11952246
TI  - Resectional therapy for cystic neoplasms of the pancreas.
AB  - Currently there is uncertainty in diagnosis between the serous (benign) and
      mucinous (premalignant) forms of cystic neoplasms of the pancreas without
      operation. Our objective is to evaluate resectional therapy as a treatment for
      these lesions. A retrospective review of cases from 1985 to 1999 were performed.
      There were 14 cases of serous cystadenoma (SCA), 11 cases of mucinous cystadenoma
      (MCA), and five cases of mucinous cystadenocarcinoma (MCAC). A female
      predominance was seen in all lesions (100% in SCA, 64% in MCA, and 80% in MCAC)
      with a mean age at presentation of 59 years. Most patients presented with pain
      (SCA = 64%, MCA = 55%, and MCAC = 80%). Weight loss was seen in 35 per cent of
      all patients and was present in all cases of MCAC. Importantly 36 per cent of MCA
      patients were asymptomatic. Lesions were identified as multicystic on CT reports
      of 62 per cent of SCA patients, 50 per cent of MCA patients and 75 per cent of
      MCAC patients. Size was similar between groups. All patients were treated with
      surgical resection; operative morbidity was 27 per cent and mortality was zero.
      Actuarial 5-year survival for SCA, MCA, and MCAC was 100, 100, and 33 per cent,
      respectively. Differentiating serous from mucinous is not possible based on
      presenting symptoms and radiologic findings. Surgical resection is justified on
      the basis of low morbidity and negligible mortality rates.

PMID- 11952247
TI  - Continuing experience with liver resection and vena cava reconstruction using
      cardiopulmonary bypass and hypothermic circulatory arrest.
AB  - When the suprahepatic vena cava or the hepatic vein confluence with the inferior
      vena cava (IVC) is obscured by tumor or a clot in the IVC extends above the
      liver, cross-clamping the IVC during liver or retroperitoneal resection is
      hazardous. This report describes a 10-year experience with ten patients who had
      liver (seven) or retroperitoneal (three) resections with vena cava reconstruction
      using cardiopulmonary bypass and hypothermic circulatory arrest. There were no
      perioperative deaths. Morbidity consisted of prolonged bile leak (one), pulmonary
      embolism (one), and stroke (one). Control of the liver was secured in six of
      seven patients who had a liver resection. There were three significant advantages
      to this technique. First, the median sternotomy provided superior exposure to the
      suprahepatic IVC. Second, the bypass technique avoided the risks of hemodynamic
      instability and prevented air embolism and sudden uncontrolled hemorrhage
      incurred by resection or IVC cross-clamping. Third, hypothermia provided a method
      of protection for residual liver function especially in the face of chronic liver
      disease induced by infection or chemotherapy.

PMID- 11952248
TI  - Extended lymphadenectomy for gastric cancer: results in a teaching hospital.
AB  - Lymphadenectomy including second-echelon lymph nodes (D2 resection) for gastric
      cancer has not been widely adopted partly as a result of a reported increase in
      operative morbidity and mortality. In the present study we examined the operative
      risk of D2 resection in a public teaching hospital. From 1995 to 1998, 57
      patients underwent exploratory laparotomy for gastric neoplasm: nine with
      curative D2 resection (Group I), 17 with curative but less than D2 resection
      (Group II), 16 with palliative resection (Group III), and 15 with no resection
      (Group IV). Among the four groups, patients with curative D2 resection (Group I)
      were older and had increased operative time and estimated blood loss, but their
      need for blood transfusion, the operative morbidity and mortality, and the mean
      hospital stay were not increased. In contrast, those patients with palliative
      resection (Group III) had the highest morbidity among all groups, the only
      fatality, and prolonged hospital stay. Therefore, curative D2 resection can be
      performed safely even with significant resident involvement. The advanced patient
      age or the extensive dissection does not increase its surgical risk. Hence, D2
      dissection should be considered whenever curative resection is feasible because
      it allows accurate staging with the added benefit of possible improvement in
      patient survival.

PMID- 11952249
TI  - An analysis of filtration and volume of radionucleotide in sentinel lymph node
      biopsy in breast cancer patients.
AB  - Controversy has occurred regarding whether to filter or not to filter the
      radionucleotide and what the optimal volume is when performing sentinel lymph
      node biopsies. To try and resolve this question we retrospectively looked at
      sentinel-node biopsies for breast cancer performed at our institution over an 18
      month period. One hundred seven patients underwent sentinel node biopsy. Ninety
      four patients had an axillary-node dissection. Twelve patients did not have a
      nodal dissection based on National Surgical Adjuvant Breast and Bowel Project
      protocol, and one patient refused dissection. Patients fell into three groups:
      Group I, filtered 8 cm3; Group II, unfiltered 8 cm3; and Group III, unfiltered 16
      cm3 (NSABP protocol). Sentinel nodes were identified in 96.3 per cent of Group I,
      84.9 per cent of Group II, and 96.3 per cent of Group III. These groups were not
      statistically different. With the addition of blue dye the ability to identify
      the sentinel lymph node was for Group I 96.3 per cent, for Group II 96.2 per
      cent, and for Group III 100 per cent. The false negative biopsy result was 0 per
      cent for all groups. The patients receiving 16-cm3 volume complained about a
      greater level of discomfort compared with the lower-volume patients. In
      conclusion neither the volume nor the filtration process affected the surgeon's
      ability to find the sentinel lymph node or the false negative rate. The higher
      injection volumes resulted in more pain. The costs and radiation exposure of the
      filtration process are not warranted.

PMID- 11952250
TI  - Ileal intussusception due to intestinal metastases from primary malignant
      melanoma of the lung.
AB  - Primary malignant melanoma of the lung (PMML) is an uncommon tumor with very few
      cases reported in the literature that satisfy the required criteria to establish
      a primary bronchial origin. We report a case of a 44-year-old man with acute
      abdominal distress and a right pulmonary roentgenographic opacity. A cranial
      thoracic-abdominal CT scan confirmed the presence of a pulmonary nodule with
      bilateral cerebral metastases and marked dilatation of intestinal loops. At
      laparotomy an ileal intussusception was noted and an ileal resection was done.
      The resected intestinal segment contained three endoluminal polypoidal
      formations. Histological and immunohistochemical analyses showed the presence of
      multiple sites of melanoma. These lesions as well as the brain lesions clearly
      appeared metastatic. The patient underwent further evaluation to identify a
      primary site of melanoma; bronchoscopy was performed with biopsy of the pulmonary
      nodule. Pathology revealed a neoplastic process of fusiform cells, with focal
      presence of melanic inter- and extracellular pigment. The immunohistochemical
      analysis confirmed the diagnosis of PMML. We discuss the criteria for diagnosis
      and histogenesis of PMML along with this unusual presentation.

PMID- 11952251
TI  - Appendiceal diverticulitis in a youth.
AB  - Appendiceal diverticulitis as the etiology of right lower quadrant pain is an
      uncommon entity in younger populations. The incidence is <1 per cent among
      patients under 30 years of age undergoing appendectomy. Herein, we present a case
      of a 17-year-old male with perforated appendiceal diverticulitis. The history,
      physical findings, diagnosis, and treatment are outlined. Additionally the
      literature concerning appendiceal diverticulitis is reviewed.

PMID- 11952252
TI  - Chronic acalculous biliary disease: cholecystokinin cholescintigraphy is useful
      in formulating treatment strategy and predicting success after cholecystectomy.
AB  - Patients with symptoms consistent with biliary colic who do not demonstrate
      calculi on routine sonography present a diagnostic dilemma for clinicians. For
      those patients in whom other disease entities have been excluded and in whom the
      history and physical examination exemplify classic signs and symptoms of biliary
      disease we show in this study that cholecystokinin cholescintigraphy with
      calculation of gallbladder ejection fraction is a predictor of pathology as well
      as subsequent symptom relief after cholecystectomy. The spectrum of pathology
      that makes up chronic acalculous biliary disease lacks a distinct definition, yet
      this review shows that cholecystokinin cholescintigraphy offers the surgeon the
      means to better counsel his or her patient with regard to surgical indications,
      options, and benefits. We reviewed 26 patients who had no gallstones detectable,
      had gallbladder ejection fraction <35 per cent, and were status postlaparoscopic
      cholecystectomy for suspected chronic acalculous biliary disease. Our results
      show histopathologic evidence of chronic cholecystitis in 100 per cent, and 92
      per cent of the patients had improvement of symptoms and satisfaction with the
      operation to the point that they would undergo the surgery again without
      reservation.

PMID- 11952253
TI  - Outcomes from peptic ulcer surgery have not benefited from advances in medical
      therapy.
AB  - Given the advancements in medical treatment of peptic ulcer disease such as
      Helicobacter pylori eradication and proton-pump inhibitors, we sought to assess
      their impact on the need for surgical intervention. Patients who underwent peptic
      ulcer surgery between 1981 and 1998 were evaluated in a retrospective chart
      review from a tertiary-care hospital (n = 222). The number of operations
      performed for peptic ulcers decreased annually (24 vs 11.3). Seventy-seven per
      cent of all cases were done urgently; most were performed for acute perforated
      ulcers. The overall 30-day mortality rate was 13 per cent, which remained
      unchanged over the past two decades. The highest mortality rate (82%) was in the
      transplanted population (n = 11). Our institutional experience demonstrates that
      despite the lower volume of patients requiring operative management a greater
      percentage of these patients are presenting with urgent need for surgery. Also
      despite the aggressive endoscopic management of acutely bleeding ulcers there was
      no change in the percentage of patients taken to the operating room for
      uncontrollable hemorrhage. Improvements in medical management of peptic ulcer
      disease have decreased the surgical volume; nevertheless we show a rising
      proportion of urgent operations performed annually, and mortality remains high.

PMID- 11952254
TI  - Empyema complicating muscle-sparing thoracotomy: the role of wound management.
AB  - The fascial layers bordering the latissimus dorsi and anchoring the serratus
      muscles often do not lend themselves to impervious closure during muscle-sparing
      thoracotomy. Fluid from the subcutaneous space may therefore drain into the
      pleural cavity after such procedures. If this fluid is contaminated with
      microorganisms the potential for development of empyema is present. Two patients
      are presented in whom this scenario was presumed to have occurred. Early
      intervention in the second patient was felt to have avoided the development of a
      major empyema.

PMID- 11952255
TI  - Giant adrenal myelolipoma.
AB  - Myelolipoma of the adrenal gland is a benign tumor comprising adipose cells and
      mature hematopoietic elements. Most of these lesions are small and asymptomatic.
      Giant myelolipomas weighing greater than 4 kg are quite rare with three other
      cases reported in the literature. A case is presented of a giant myelolipoma that
      was resected surgically. The literature is reviewed regarding this topic with
      emphasis on diagnostic and therapeutic implications.

PMID- 11952256
TI  - Radiofrequency ablation of recurrent cholangiocarcinoma.
AB  - Intrahepatic recurrence of cholangiocarcinoma after primary resection has
      traditionally been considered a contraindication to surgical management.
      Improvements in ablative technologies such as radiofrequency ablation (RFA) offer
      the surgeon additional alternatives in the management of selected intrahepatic
      tumors. We present a case report of a single intrahepatic recurrence of
      cholangiocarcinoma 12 months after primary resection of extrahepatic
      cholangiocarcinoma including right lobectomy for intrahepatic extension. The
      patient received operative treatment and RFA of the intrahepatic lesion. RFA
      successfully ablated the recurrent tumor, and the patient remains free of
      detectable disease 10 months later. A review of literature is presented. This is
      the first known report of the use of RFA for intrahepatic cholangiocarcinoma. In
      selected cases of primary or recurrent cholangiocarcinoma, RFA may increase the
      percentage of patients considered surgically treatable.

PMID- 11952257
TI  - The influence of gender of the surgeon on surgical procedure preference for
      breast cancer.
AB  - There are few data in the literature with regard to the influence of surgeon
      gender and the treatment of breast cancer. In this retrospective review we
      propose to test the hypothesis that male surgeons are just as likely as female
      surgeons to provide breast-conservative treatment. From 1990 through 1997 2271
      women with breast cancer in Cincinnati, Ohio were operated on by surgeons within
      the TriHealth Corporation. We compared the performance rate of breast
      conservation therapy (BCT) with the rate of mastectomy in early-stage breast
      cancer patients between male and female surgeons. Male surgeons were
      significantly more likely to provide their patients with breast-conserving
      treatment than their female colleagues for stages 0 and IIb (P < 0.05). Although
      male surgeons performed more BCT than female surgeons for stages I and IIa the
      difference was not statistically significant. For the three stages combined there
      was a 30 per cent greater chance of a patient receiving breast-conserving
      treatment if she went to a male surgeon (P < 0.05). We conclude that in our
      institution male surgeons are no more likely to select mastectomy than their
      female colleagues and there appears to be an increased use of BCT by male
      surgeons.

PMID- 11952258
TI  - Percutaneous subclavian central venous catheterization in children younger than
      one year of age.
AB  - Children younger than one year of age frequently require central venous lines
      (CVLs) for total parenteral nutrition, intravenous antibiotics, and chemotherapy.
      In many instances surgical cut-down has been favored over percutaneous access.
      The purpose of this study was to demonstrate the safety and success of
      percutaneous central venous access in children less than one year of age.
      Percutaneous access of the subclavian vein was obtained by Seldinger technique.
      Using the medical procedure code index we reviewed the charts of those patients
      less than one year of age from January 1, 1999 through December 31, 1999
      requiring central venous access. Age, diagnosis, number of CVLs required, site
      placed, success rate, and weight were recorded. In 1999 a total of 84 patients
      younger than one year of age received a total of 110 CVLs. In patients less than
      6 months of age the success rate for percutaneous access of the subclavian vein
      was 78.8 per cent and for those children over 6 months the success rate was 96
      per cent. The average weight for those less than 6 months was 3.1 kg and for
      those older than 6 months was 7.63 kg. There were no complications from the
      procedure. Percutaneous CVL placement in children younger than one year of age is
      safe and effective. This paper details our technique and reviews infant venous
      anatomy in the subclavian area.

PMID- 11952259
TI  - Re: Surgical treatment of severe colonic inertia with restorative
      proctocolectomy.

PMID- 11952260
TI  - Center-based care for young children: examining predictors of quality.
AB  - The authors collected information from caregivers, trained observers, and parents
      to investigate quality elements in child-care programs designed for young
      children in center-based settings. Participants were 75 parents of children aged
      15 to 36 months and their caregivers from 13 child-care centers in a southeastern
      state. Observers collected indicators of program quality and process and
      structural quality indicators, including adult-child ratio, group size, use of
      planned activities, use of child-designated space, housekeeping activities, and
      caregiver-child interactions. Participants responded to questions regarding their
      child-rearing beliefs, social support networks, perceived stress levels, and
      demographic characteristics. The best predictors of higher quality care and
      sensitive caregiver-child interaction in centers were specialized caregiver
      training, higher adult-child ratios, use of planned activities, and less
      perceived stress by caregivers. Implications of these findings are discussed.

PMID- 11952261
TI  - Leftward cradling bias, prosodic speech, and deafness: the deaf are not dumb.

PMID- 11952262
TI  - Parents think their sons are brighter than their daughters: sex differences in
      parental self-estimations and estimations of their children's multiple
      intelligences.
AB  - In this study, 156 participants, predominantly White British adults (M age = 44.3
      years) rated themselves on overall IQ and on H. Gardner's (1983) 7 intelligence
      subtypes. Parents (n = 120) also estimated the intelligence of their children.
      Men's self-estimates were significantly higher than women's (110.15 vs. 104.84).
      Participants thought their verbal, mathematical, and spatial intelligence scores
      were the best indicators of their own overall intelligence. Parents estimated
      that their sons had significantly higher IQs than their daughters (115.21 vs.
      107.49). Self-estimates and estimates of children's multiple intelligences were
      higher for men and sons, significantly so for logical-mathematical and spatial
      intelligence. Parents rated 2nd-born daughters as having significantly higher
      verbal and musical intelligence than their male counterparts. Higher parental IQ
      self-estimates corresponded with higher IQ estimates for children. Results for
      1st-born children were clearest and showed the most significant differences. The
      findings are interpreted in terms of sociocultural and familial influences and
      the possibility of actual sex differences in particular abilities.

PMID- 11952263
TI  - Argument structure, argument content, and cognitive change in children's peer
      interaction.
AB  - In this experimental study, the author examined whether children's conversations
      play a role in the processes of influence between peers. Children, aged 8 to 10
      years, who were at different levels of moral development participated. The
      conversations of 120 children were coded and analyzed in terms of argument
      structure and content. Results indicated that the differences in structure
      between boys' and girls' arguments are stylistic and do not influence
      conversation outcomes. The children's use of the structural features of
      conversations suggested that when a more advanced position is adopted, the
      arguments themselves appear to inspire cognitive change. However, when a less
      advanced position is adopted, the children who influence their peers invoke a
      particular and insistent conversational style. Results are discussed in terms of
      transmission and constructivist accounts of the role of social interaction in
      cognitive development.

PMID- 11952265
TI  - Perception of genuine and masking smiles in children and adults: sensitivity to
      traces of anger.
AB  - The authors examined children's and adults' sensitivity to traces of anger in
      masking smiles by presenting participants with short video excerpts of smiles
      that differed by the intensity of an anger component. Fifty-two children, aged 6
      to 12 years, and 26 adults were asked to judge whether a stimulus person was
      really happy or pretending to be happy. Six- and 7-year-old children were found
      to be sensitive to traces of anger, but less so than older children and adults.
      Researchers found evidence of explicit knowledge of the emotion hidden in masking
      smiles only in adult participants.

PMID- 11952264
TI  - Coping in adolescent children of HIV-positive and HIV-negative substance-abusing
      fathers.
AB  - The authors examined coping in the adolescent children of drug-abusing fathers
      who have, or are at risk for contracting, human immunodeficiency virus (HIV). The
      ability to cope is an important factor in the adolescent's own risk behaviors,
      including drug use and associated problems. Each father and his adolescent child
      were separately administered a structured interview regarding personality, drug
      use, relationships, coping, and other behaviors. Adolescent adaptive coping was
      found to be related to greater conventionality, less marijuana use, fewer intra-
      and interpersonal problems, paternal adaptive coping, and a close father-child
      bond. Moreover, analysis using a risk factor index indicated an exponential
      increase in adolescent maladaptive coping with each additional psychosocial risk.
      Implications for policy and intervention are also discussed.

PMID- 11952266
TI  - Behavior problems and peer rejection in preschool boys and girls.
AB  - The authors tested the hypothesis that deviant behaviors within a preschool peer
      group would be linked with peer rejection, irrespective of child gender. Seventy
      six children, aged 3 to 5 years, participated. Teachers rated children's behavior
      on the Child Adaptive Behavior Inventory, and children provided sociometric
      ratings. For a subsample of children (n = 47), observers coded aggressive,
      noncompliant, and withdrawn behavior using a time-sampling system. For both boys
      and girls, noncompliance, hyperactivity, and social withdrawal were associated
      with peer rejection; overt aggression was associated with peer rejection for
      boys, but not for girls. Analysis revealed that approximately half of the
      variance in sociometric and teacher ratings of peer rejection was accounted for
      by aggression and social withdrawal for both boys and girls. The results suggest
      that the association between behavior problems and peer rejection emerges at a
      very early age.

PMID- 11952267
TI  - A study of posttraumatic stress in a student population.
AB  - The authors examined the incidence of posttraumatic stress (PTS), with respect to
      levels of exposure to traumatic events, in a British student population.
      Respondents (N = 700) completed a standard questionnaire booklet that contained a
      posttraumatic stress disorder interview. The questionnaire collected personal
      demographic information and was used by researchers to ascertain whether
      respondents had experienced a traumatic event. Consistent with previous American
      studies, PTS was found to be relatively common; 23.3% of the sample showed either
      current or past PTS. Female participants had a significantly higher incidence of
      PTS than did male participants, although the latter were more likely to report
      having experienced a traumatic event. The experience of trauma was significantly
      associated with the likelihood of PTS. The authors discuss implications of their
      results in terms of long-term consequences of unresolved trauma.

PMID- 11952268
TI  - Children's emotional reactivity to interadult nonverbal conflict expressions.
AB  - The authors investigated children's responses to nonverbal expressions of
      conflict. Reactions of 3 groups of children (ranging in age from 6 to 16 years)
      to multiple forms of nonverbal conflict behaviors expressed in videotaped
      simulations of interadult disputes were examined. Results indicated that children
      make few discriminations between different forms of nonverbal conflict behaviors
      and that their reactions to nonverbal conflict are similar to their reactions to
      verbal conflict. Adults' expressions of fear elicited the most negative emotional
      responses from children, suggesting that children react to the meaning of
      conflict expressions and that expressions of fear may represent the greatest
      emotional security risks to children. Implications of these results for a
      theoretical model of the effects of forms of marital conflict on children are
      discussed (P. T. Davies & E. M. Cummings, 1994).

PMID- 11952270
TI  - Minimally invasive surgery for coronary artery disease with associated lung
      cancer.
AB  - Simultaneous surgical management of patients with co-existing ischemic heart
      disease and lung carcinoma remains controversial. Traditionally, these operations
      have been staged, with coronary artery revascularization first, followed by
      pulmonary resection at a later date. Under this procedure, tumor resection is
      delayed, and these staged procedures may increase morbidity and cost. Our
      experience with minimally invasive surgery in the cardiac and thoracic fields
      suggests that both diseases can be resolved within the same operation. This
      report presents a 65-year-old man with coronary artery disease (CAD), and left
      lung cancer. He received concomitant coronary artery bypass grafting for CAD and
      pulmonary resection for lung cancer via a left parasternal minithoracotomy. No
      complaints or clinical signs were observed during a 6 month follow-up. Therefore,
      major cardiac and thoracic procedures that are performed via a minimally invasive
      approach using conventional instruments, can result in a safer, quicker, and more
      economical procedure. The results of the a minimally invasive approach
      demonstrated the technical feasibility of treating a triple vessel cardiac
      disease with lung cancer.

PMID- 11952269
TI  - Helical computed tomography of the abdomen: evaluation of image quality using
      1.0, 1.3, and 1.5 pitches.
AB  - BACKGROUND: The purpose of this study was to investigate whether trained
      radiologists can distinguish minor differences among computed tomography (CT)
      images of extended helical pitches of 1.0 to 1.5. METHODS: Between September 2000
      and February 2001, 72 patients were randomized into 1 of 3 equal groups: helical
      pitches of 1.0, 1.3, and 1.5. The imaging parameters of all patients were kept
      constant. Twelve of the 72 patients were excluded because of various pathological
      conditions. In a total, 60 examinations were enrolled in the evaluation study.
      Three radiologists blinded to the image parameters were asked to independently
      evaluate 9 normal structures and overall images of 60 studies using a scale from
      1 (worst) to 5 (best). RESULTS: There were no statistically significant
      differences in evaluation of image quality among helical pitches 1.0, 1.3, and
      1.5 of abdominal CT when assessing 9 normal structures and overall images
      independently (p > 0.05). CONCLUSIONS: Abdominal CT performed with helical
      pitches of 1.0, 1.3, and 1.5 were equivalent in this study. With the use of a
      helical pitch greater than 1, clinicians can benefit from increased scan coverage
      in less time and with less radiation than can be achieved with standard helical
      pitch-1.0 protocols.

PMID- 11952271
TI  - Simultaneous occurrence of gastric adenocarcinoma and low-grade gastric lymphoma
      of mucosa-associated lymphoid tissue.
AB  - Gastric adenocarcinoma developing concomitantly with a gastric lymphoma of the
      mucosa-associated lymphoid tissue (MALT) type is rare. Herein, we report a case
      with a synchronous primary gastric MALT lymphoma and an early adenocarcinoma of
      the stomach. A 72-year-old patient with initial presentation of weight loss was
      found with endoscopy to have a large tumor mass in the gastric body. Pathologic
      examination of biopsies revealed a low-grade MALT lymphoma for which chemotherapy
      with cyclophosphamide, vincristine, and prednisolone was administered. A gastric
      adenocarcinoma was found at a different site in the of stomach 3 months after
      cessation of chemotherapy when there was still residual MALT lymphoma in the
      stomach. The presence of double neoplasms was established preoperatively. The
      patient underwent a proximal gastrectomy. Infection with Helicobacter pylori (H.
      pylori) was detected once in the repeated endoscopic gastric biopsies. The
      occurrence of both gastric MALT lymphoma and gastric adenocarcinoma was reviewed
      and the association of H. pylori infection with both malignancies is discussed.

PMID- 11952272
TI  - Percutaneous trigeminal ganglion compression for the treatment of trigeminal
      neuralgia: report of two cases.
AB  - Percutaneous trigeminal ganglion compression for the relief of trigeminal
      neuralgia is a technically simple, non-painful procedure, carried out under brief
      general anesthesia. The patients could tolerate well during the treatment. The
      operation successful rate is high, and the procedure can be repeated at the next
      day if the symptom was not relieved. The procedure, in the present, is the first
      choice for those trigeminal neuralgia patients who are poor medical risks, those
      who are above the age of 65, those with demyelinating disease, and those who are
      unwilling to accept the increased risk of a posterior fossa craniectomy. We have
      successfully performed this procedure for two recurrent trigeminal neuralgia
      patients without any surgical complication. We propose this surgical treatment
      algorithm for trigeminal neuralgia patients who are not able to tolerate the
      medical treatment.

PMID- 11952273
TI  - High-density vitreous substitute in the management of advanced Coats' disease.
AB  - Advanced Coats' disease is a threat to vision. Management of advanced Coats'
      disease has long been a challenge to ophthalmologists. Some people have attempted
      to use pars plana vitrectomy and intraocular diathermy on diseased vessels
      followed by intraocular gas or silicone oil injection. However, internal drainage
      is technically difficult. We present a case of advanced Coats' disease for which,
      after an encircling buckle and pars plana vitrectomy, intravitreal injection of
      perfluorodecaline was used to displace the subretinal fluid to the peripheral
      subretinal space, and transscleral external drainage was achieved. Finally
      panretinal laser photocoagulation, cryotherapy and endodiathermy were performed
      on diseased vessels. Visual improvement and reattachment of the posterior pole
      were achieved. So we think a high-density vitreous substitute can be a useful
      adjunct in the management of advanced Coats' disease. It minimizes the
      disadvantages of the internal or external approaches, while maintaining most of
      the advantages of both.

PMID- 11952274
TI  - Aortic root pseudoaneurysm following surgery for aortic valve endocarditis.
AB  - Prosthetic aortic valve replacement for aortic valve endocarditis remains a
      primary practice of most cardiac surgeons. Usually it cures endocarditis and
      restores cardiac function. However, in advanced aortic valve endocarditis with
      complex annular destruction, complications following prosthetic aortic valve
      replacement do occur and present a formidable challenge for reoperation. Herein,
      we describe a case of an adult man who was operated on initially for advanced
      aortic valve endocarditis with a large periannular abscess cavity and who
      developed congestive heart failure 3 months later. Furthermore, he was diagnosed
      with a giant pseudoaneurysm around the aortic root without evidence of recurrent
      infection or aortic prosthetic incompetence. During his reoperation, a
      cryopreserved aortic homograft as a root replacement that included reimplantation
      of bilateral coronary artery buttons was used to exteriorize this pseudoaneurysm
      and reconstruct a left ventricular outflow tract. The postoperative course was
      unremarkable, and the patient, during a follow-up of 2 years, remained in New
      York Heart Association functional class I. Aortic root pseudoaneurysm following
      prosthetic aortic valve replacement for infective endocarditis is rare in
      clinical practice and can cause rapid hemodynamic deterioration which requires
      imminent reoperation. Homograft aortic root replacement has proven to be a
      versatile treatment option of this complex disease.

PMID- 11952275
TI  - Pulmonary function impairment in pneumoconiotic patients with progressive massive
      fibrosis.
AB  - BACKGROUND: Progressive massive fibrosis (PMF) is the severe form of coal
      workers' pneumoconiosis (CWP). Clinical observations have suggested that the
      components of PMF are inhomogenous. There may be a significant diversity in the
      magnitude of pulmonary impairment for miners with PMF. This study is intended to
      investigate the relationship between radiological categories of PMF and pulmonary
      impairment. METHODS: Eighty-six coal workers with radiological evidence of PMF
      were enrolled. They were subdivided into 3 categories, i.e., A, B, and C
      according to the International Labour Office (ILO) classification. Maximal
      expiratory flow-volume curves and diffusing capacity were measured in each
      subject. RESULTS: Our data reveal that forced vital capacity (FVC) and forced
      expiratory volume in 1 s (FEV1) were abnormally low in all categories. However,
      FVC was only mildly reduced in category A, and then rapidly decreased with the
      progression of radiological category. The major pattern of impairment for miners
      with PMF was obstructive, but there was an increasing trend for restrictive
      impairment for higher radiological categories. A normal spirogram was still
      observed in 6-11% of subjects in category A and even B. For diffusing capacity
      (DLCO), there was also a progression of impairment with transition from category
      A to categories B and C. Smoking miners had even lower FEV1/FVC and DLCO than did
      their non-smoking counterparts. CONCLUSIONS: Pulmonary impairment increased with
      increasing radiological category even in PMF. Assessment of lung function should
      be individualized and carried out with a combination of tests, i.e., spirometry
      and DLCO measurement. The loss of lung function cannot be accounted for by
      different smoking habits.

PMID- 11952276
TI  - Efficacy of topical microfibrillar collagen mixed with steroid hormone and
      morphine for postoperative pain control during lumbar laminectomy: a preliminary
      report.
AB  - BACKGROUND: Current inpatient management of postoperative pain in lumbar surgery
      includes the use of intramuscular opioid analgesics, nonsteroidal anti
      inflammatory drugs, or patient-controlled analgesia; however, all types of
      medications are associated with side effects that can limit their usefulness in
      the inpatient setting. METHODS: In a well-conducted non-randomized prospective
      trial, 80 consecutive patients who underwent elective multilevel lumbar
      laminectomy surgery were identified. Two types of trials with different doses of
      steroids were used. Patients' preoperative medical records, pain scores,
      narcotics consumption, costs for the regimen, hospital stay, unwanted
      complications, and walking ability were evaluated postoperatively. RESULTS: Pain
      in patients after lumbar surgery can be dramatically controlled postoperatively.
      Seventy-eight patients (97.5%) were able to walk without support on the first
      postoperative day. Major side effects were found in 5 patients (6.2%).
      CONCLUSIONS: This experience indicates that pain-control agents with epidural
      sustained-released preparation seem to be beneficial in early mobilization, are
      cost effective, and require lower analgesic consumption by patients. Similar pain
      control can be obtained with lower doses of methylprednisolone. In spite of its
      clinical attractiveness, improvements in the side effects of complications from
      epidural morphine and the combination of steroids and microfibrillar collagen
      have yet to be realized.

PMID- 11952277
TI  - Safety and effectiveness of minimal-access versus conventional coronary artery
      bypass grafting in emergent patients.
AB  - BACKGROUND: Myocardial revascularization with a minimal-access incision is used
      in many patients who undergo an elective coronary artery bypass grafting (CABG)
      operation. To evaluate whether this method could be used for patients who undergo
      an emergent CABG operation, we compared patients in whom emergent minimal-access
      CABG was used as the method of revascularization with patients who underwent
      emergent conventional CABG. METHODS: From June 1996 to April 1998, 63 patients
      underwent emergent CABG operation due to unstable angina, percutaneous
      transluminal coronary angioplasty accident, or critical left main lesion. Ten
      patients received minimal-access CABG via limited left parasternal incision (MI),
      and 53 patients received conventional CABG via median sternotomy (CS). RESULTS:
      There were 2 deaths in the MI group and 13 deaths in the CS group. We used the
      Society of Thoracic Surgery computer program to predict the mortality of both
      groups. The expected hospital mortality of the MI group was significant higher
      than that of the CS group. The 24-hour drainage amount in the MI group was
      significant less than that of the CS group. There were no significant differences
      in cross-clamping time, the duration of extracorporeal circulation, the intensive
      care unit stay, or the average hospital stay. Total costs of the MI group were
      similar to those of the CS group, except that the blood transfusion fee was
      significantly lower (9,406 +/- 1,259 vs. 12,059+ 3,994 New Taiwan dollars, p =
      0.003). CONCLUSION: This technique combines minimally invasive surgical
      conditions with the safety and cost standards of emergent CABG surgery. Even
      emergent and high-risk coronary artery disease can be treated using this
      approach.

PMID- 11952278
TI  - Needling revision with subconjunctival 5-fluorouracil in failing filtering blebs.
AB  - BACKGROUND: 5-Fluorouracil, an antimetabolic agent, improves the success rate of
      trabeculectomies by inhibiting subconjunctival fibrosis. However, complications
      may be associated with early postoperative use. We investigated the outcome of
      needling revision with delayed subconjunctival 5-fluorouracil in failing
      filtering blebs after a trabeculectomy in patients with medically poorly
      controlled glaucoma. METHODS: We performed needling revision with subconjunctival
      5-fluorouracil injection 5.0 +/- 4.0 weeks after trabeculectomy with failing
      filtering blebs in 25 eyes of 24 patients. The diagnoses of these patients were
      primary angle-closure glaucoma (4), primary open-angle glaucoma (4), post-cornea
      graft glaucoma (8), traumatic glaucoma (5), neovascular glaucoma (3) and
      pseudophakic glaucoma (1). RESULTS: Total success was achieved in 21 eyes (84%)
      including complete success in 10 (40%) and qualified success in 11 (44%) after
      3.2 +/- 1.2 needling revisions over an average 8.3 +/- 7.0-month follow-up period
      from the last needling revision. The mean intraocular pressure was 16.0 +/- 8.4
      mmHg in the last visit compared with 26.0 +/- 8.1 mmHg before the procedure.
      Major complications were transient hypotony (1), transient corneal epithelial
      defect (13) and hyphema (3). CONCLUSIONS: This study supports the efficacy and
      safety of the delayed use of 5-fluorouracil with needling revision for managing
      failing filtering blebs following a trabeculectomy.

PMID- 11952279
TI  - Alcohol use among women of childbearing age--United States, 1991-1999.
AB  - Prenatal exposure to alcohol is one of the leading preventable causes of birth
      defects, mental retardation, and neurodevelopmental disorders in the United
      States. One of the national health objectives for 2010 is to increase to 94% the
      percentage of pregnant women abstaining from alcohol use [corrected]. During 1991
      1995, alcohol use by pregnant women increased substantially, and alcohol use by
      nonpregnant women of childbearing age increased slightly. To characterize trends
      in alcohol use among women of childbearing age, CDC analyzed representative
      survey data from the Behavioral Risk Factor Surveillance System (BRFSS) during
      1991-1999. This report summarizes the results of the analysis, which indicate
      that the rate of any alcohol use (i.e., at least one drink) during pregnancy has
      declined since 1995. However, rates of binge drinking (i.e., > or = 5 drinks on
      any one occasion) and frequent drinking (i.e., > or = 7 drinks per week or > or =
      5 drinks on any one occasion) during pregnancy have not declined among
      nonpregnant women of childbearing age. Health-care providers should routinely
      screen women of childbearing age for alcohol use and counsel them about the
      adverse effects of alcohol use during pregnancy.

PMID- 11952280
TI  - Update: Influenza activity--United States, 2001-02 season.
AB  - Although data collected from the four components of the CDC influenza
      surveillance system are preliminary, national influenza activity appears to have
      peaked during the week ending February 23, 2002 (week 8). During the 2000-01 and
      1999-2000 influenza seasons, peak activity occurred during week 4 and week 51,
      respectively. The viruses most commonly isolated during the 2001-02 season have
      been influenza A (H3N2). These viruses were well-matched antigenically by the
      2001-02 influenza A (H3N2) strain in the vaccine. This report summarizes
      influenza activity in the United Statest during September 30, 2001-March 23,
      2002, and updates previous summaries from this season.

PMID- 11952281
TI  - Suspected cutaneous anthrax in a laboratory worker--Texas, 2002.
AB  - On March 6, 2002, CDC's National Institute for Occupational Safety and Health
      (NIOSH) received a request for a health hazard evaluation from the director of
      Laboratory A to assist in the evaluation of a worker who had been diagnosed with
      cutaneous anthrax. Laboratory A, a provisionally approved Laboratory Response
      Network level B laboratory, had been processing environmental samples for
      Bacillus anthracis in support of CDC investigations of the bioterrorist attacks
      in the United States during fall 2001. Since March 7, CDC has interviewed the ill
      laboratory worker and other workers at the laboratory and conducted environmental
      assessments of the workplace. This report summarizes the epidemiologic and
      environmental investigation of this case, which indicates that the likely source
      of exposure was the surface of vials containing B. anthracis isolates that the
      worker placed in a freezer on March 1. Laboratory workers handling specimens of
      B. anthracis should follow recommended procedures to minimize the risk of B.
      anthracis transmission and anthrax.

PMID- 11952282
TI  - Imported dengue--United States, 1999 and 2000.
AB  - Dengue is a mosquito-transmitted acute viral illness caused by any of the four
      dengue virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4). Dengue is endemic in
      most tropical and subtropical areas of the world and has occurred among U.S.
      residents returning from travel to such areas. CDC maintains a laboratory-based
      passive surveillance system for imported dengue among U.S. residents (laboratory
      diagnosed dengue in a U.S. resident living in an area without known
      authochthonous dengue transmission, with travel history outside the United States
      in the 14 days before symptom onset). The system relies on reports by clinicians
      to state health departments, which forward patient specimens to CDC for
      diagnostic testing. This report summarizes information about imported dengue
      cases among U.S. residents during 1999-2000. The findings indicate that dengue
      continues to cause disease in U.S. travelers abroad. Travelers to tropical areas
      should protect themselves from mosquito bites, and health-care providers should
      consider dengue in the differential diagnosis of illness for patients who have
      returned recently from such areas.

PMID- 11952283
TI  - Treatment principles of atopic dermatitis.
AB  - Atopic dermatitis (AD) is today the most common, chronic inflammatory skin
      disease among children in developed countries. Its cumulative prevalence varies
      from 20% in northern Europe and the USA to approximately 5% in Mediterranean
      countries. As a chronic disease it puts a special demand on treatment. There is
      no curative therapy, but competent guidance on treatment principles can control
      the disease in most, if not all children. This article summarizes the evidence
      based knowledge that relates to the treatment of atopic eczema. It also gives
      advice and opinions on prophylactic measures as these are the focus of interest
      from most parents. LEARNING OBJECTIVE: This article should enable you to give
      advice and guidance to parents of children with AD, including what is necessary
      for diagnosis, what is of value and importance considering allergies and
      allergological investigations, allergen exposure, prophylactic measures, diets
      and indoor environment. Finally, you should be able to explain the diversity of
      treatment principles for parents.

PMID- 11952284
TI  - Unusual causes of cutaneous ulcerations.

PMID- 11952285
TI  - Laser treatment of cutaneous vascular lesions: face and leg telangiectases.

PMID- 11952286
TI  - Pityriasis versicolor.
AB  - Pityriasis versicolor is a common superficial fungal infection of the skin. It is
      caused by Malassezia spp., which are normal human saprophytes. Under certain
      conditions, both exogenous and endogenous, the fungus can convert from a yeast to
      a pathogenic mycelial form. This alteration results in mild inflammation of the
      skin, and in characteristic clinical and histological changes. The taxonomy of
      Malassezia spp. has recently been modified to include six obligatorily lipophilic
      species, all of which can be found on human skin, plus one non-obligatorily
      lipophilic species, which only rarely colonizes human hosts. LEARNING OBJECTIVES:
      At the conclusion of this learning activity, participants should be aware of the
      role of Malassezia in the development of pityriasis versicolor, the clinical and
      histological changes arising from this dermatosis, and the diagnosis and
      treatment of this disorder.

PMID- 11952287
TI  - Molecular analyses of sentinel lymph nodes: an open question.
AB  - AIMS: To detect micrometastases in the sentinel lymph nodes (SLN) of melanoma
      patients the authors analysed 52 lymph nodes (47 SLNs and five non-sentinel) and
      17 corresponding primary skin melanomas using reverse transcriptase-polymerase
      chain reaction assays in paraffin-embedded tissues to detect the mRNAs of
      tyrosinase, MAGE1, MAGE3, MIA, MART-1 and mRNA coding for telomerase catalytic
      component. RESULTS: Our data show that the use of molecular markers for melanoma
      micrometastases detection in SLN is still in a very preliminary stage. In
      comparing the molecular analysis results with the pathological staging we did not
      find any evident correlation with the expression of the analysed genes in SLN.
      There are no data for judging the prognostic significance of the detection of
      circulating tumour cells in patients without clinically recognizable metastases.
      Despite progress in the field with simultaneous detection of several markers it
      was assumed that tyrosinase mRNA remains the best target for the detection of
      metastatic melanoma cells.

PMID- 11952288
TI  - Adjuvant botulinum toxin A in dyshidrotic hand eczema: a controlled prospective
      pilot study with left-right comparison.
AB  - OBJECTIVE: Dyshidrotic hand eczema is a therapeutic challenge. A prospective
      pilot study was performed with left-right comparison in order to investigate
      whether chemical de-innervation of sudoriferic nerves would be superior to
      standard therapy with topical corticosteroids. BACKGROUND: Botulinum toxin A
      (BTXA) is a potent inhibitor of acetylcholine release, that induces eccrine sweat
      production and release. Inhibition of sweating by other measures such as tap
      water iontophoresis has been shown to be beneficial in dyshidrotic hand eczema.
      METHODS: Eight adult patients suffering from dyshidrotic hand eczema (atopic
      type) were included in a prospective, side-by-side controlled clinical pilot
      study using topical corticosteroids on both hands in combination with
      intracutaneous injections of 100 units of BTXA (Botox) on the more severely
      affected hand on day 1. The dyshidrotic hand eczema was classified using the DASI
      (Dyshidrotic Eczema Area and Severity Index) before treatment (0), after 1 week,
      4 weeks and 8 weeks. RESULTS: Six patients completed the study, two dropped out
      because of social and personal reasons. The mean DASI score changed from 28 to17
      with topical therapy alone and from 36 to 3 with adjuvant BTXA (P < 0.01).
      Itching and vesiculation were inhibited earlier when using the combination of
      corticosteroids and BTXA. There was one relapse in the corticosteroid group.
      Relapses have not been seen in the BTXA group. CONCLUSIONS: Interruption of
      sweating by BTXA improves the outcome and reduces relapses in patients with
      dyshidrotic hand eczema. BTXA is antipruritic as well suggesting that it does not
      only interact with acetylcholine release but substance P.

PMID- 11952289
TI  - Hepatitis B and hepatitis C virus infections in dermatological patients in west
      Sicily: a seroepidemiological study.
AB  - OBJECTIVES: To evaluate the relative frequencies and molecular epidemiological
      features of viral hepatitis types B and C in dermatological patients in our
      geographical area. METHODS: We determined the hepatitis B virus (HBV) and
      hepatitis C virus (HCV) antibodies and the hepatitis B virus surface antigen
      (HBsAg) in a cohort of 677 dermatological patients admitted to the Department of
      Dermatology of Palermo. An 8-mL blood sample was taken from all subjects. The
      following assays were used: HBsAg, anti-HB core (antigen) (anti-HBc), anti-HB
      surface (antigen) (anti-HBs), anti-HB early (antigen) (anti-Hbe) and anti-HCV
      antibodies using enzyme-linked immunosorbent assay. RESULTS: One hundred and
      eighty-nine (27.91%) of the 677 dermatological patients were positive for anti
      HBc, anti-HBs, anti-HBe and/or anti-HCV antibodies. In particular 22% (149
      patients) were anti-HBc, anti-HBs or anti-HBe positive, reflecting exposure to
      HBV, and six patients (0.88%) were chronic carriers of HBsAg; 2.36% of the
      dermatological patients (16 persons) were anti-HCV positive. Tests showed that 24
      subjects (3.52%) were infected with hepatitis B or C. The peaks in the age bands
      were in the 55-80-year-old age groups. CONCLUSIONS: This study confirms a high
      rate of HBV and HCV exposure with chronic carriers in our dermatological
      patients. We assume that the high prevalence of HCV and HBV in dermatological
      patients is more likely to be age related than to represent a true and direct
      association with dermatological diseases in general. Definite conclusions will
      only be available after large epidemiological studies that can establish or
      refute an aetiological and pathogenetic role of HBV and HCV in certain skin
      diseases associated with liver infection.

PMID- 11952290
TI  - Sun awareness and sun protection practices in Malta.
AB  - BACKGROUND: Concern regarding the rising incidence of melanoma and non-melanoma
      skin cancers in Malta has led to the organization of annual campaigns since the
      early 1990s. These aim to inform the public of the dangers of sun exposure and to
      promote sun protection. OBJECTIVE: To help guide future campaigns, a survey was
      carried out to evaluate current sun protection measures among the Maltese people
      and to assess their level of knowledge regarding harmful effects of the sun on
      the skin. STUDY DESIGN: A total of 559 pedestrians were interviewed in the main
      street of the capital city of Malta in the summer of 1999. RESULTS: Self-reported
      rates of regular sunscreen and hat use in adults exposed to the spring/summer sun
      between 10.00 h and 15.00 h were 51% and 32%, respectively, for leisure
      activities, and 25% and 37%, respectively, for outdoor work. Men reported using
      sunscreen less often than women during both leisure and work. The fairer-skinned
      outdoor workers actually reported making less use of a sunscreen and/or hat than
      their darker counterparts, and rates of sunscreen and/or hat use during leisure
      and work were not found to increase with the amount of time spent in the sun.
      Almost 75% of sunscreen users were using a sun protection factor of at least 15.
      Parents reported much higher rates of regular sunscreen and hat use by their
      young children than by themselves, with 87% of children under 12 years of age
      reported to be using sunscreen and 78% reported to be wearing a hat. The great
      majority knew that injudicious sun exposure is associated with skin cancer and
      skin ageing, but 48% were still regarding a suntan achieved without skin burning
      as 'healthy' The mass media was by far considered to be the main source of
      information for the general public regarding effects of the sun on the skin.
      CONCLUSIONS: The positive impact of past campaigns can be seen in the high
      reported rates of sun protection in children. However, much remains to be done
      with adults in order to change their attitude about a 'healthy suntan' and to
      convince them that it is worthwhile to protect themselves from the sun.

PMID- 11952291
TI  - Early diagnosis of herpes zoster by polymerase chain reaction.
AB  - BACKGROUND: Herpes zoster is a common disease caused by the varicella-zoster
      virus. The use of virostatic agents as early as possible is necessary in
      shortening zoster-associated pain. OBJECTIVES: Rapid diagnosis is necessary for
      the optimal efficacy of antiviral therapy. The diagnosis in the early stage of
      infection is often difficult. METHODS: In the present study skin biopsies of
      patients with herpes zoster and unclear skin changes were analysed by detecting
      viral DNA using the polymerase chain reaction (PCR) in order to amplify open
      reading frames (ORF) 14, 29 and 63. RESULTS: Varicella-zoster virus DNA could be
      detected with PCR of all three ORF not only from blisters but also from
      erythematous skin. CONCLUSIONS: PCR is the method of choice for the viral
      diagnosis in herpes zoster before blister eruption.

PMID- 11952292
TI  - Imiquimod 5% cream is an acceptable treatment option for external anogenital
      warts in uncircumcised males.
AB  - OBJECTIVES: To determine the safety and efficacy of imiquimod (Aldara) 5% cream
      in the treatment of prepuce-associated warts in uncircumcised males. METHODS: An
      open-label study in six UK medical centres with 35 uncircumcised males with
      prepuce-associated warts treated with imiquimod 5% cream three times per week for
      up to 16 weeks. Other anogenital warts were also treated. RESULTS: Three times
      weekly application of imiquimod was found to be safe, with erythema as the most
      commonly reported local skin reaction. Forty per cent of patients had complete
      clearance of anogenital warts within 16 weeks. CONCLUSIONS: Imiquimod cream at a
      dosing regimen of three times per week, is effective and has an acceptable safety
      profile in the treatment of prepuce associated warts and other external
      anogenital warts in uncircumcised males.

PMID- 11952293
TI  - Personality dimensions of sexually transmitted disease repeaters assessed with
      the Millon Clinical Multiaxial Inventory.
AB  - OBJECTIVE: To assess the personality characteristics of patients with repeated
      sexually transmitted diseases (STD). METHOD: A case-control study comparing 101
      STD repeaters (subjects with a lifetime history of three or more STDs) with 182
      controls who had no history of STD. All subjects attended the City Department for
      Skin and Venereal Diseases in Belgrade (Yugoslavia) from June 1997 to April 1998.
      Personality characteristics was assessed by the Millon Clinical Multiaxial
      Inventory (MCMI). RESULTS: The analysis of MCMI test showed that STD repeaters
      had higher scores on narcissistic, antisocial and paranoid scales. The difference
      between STD repeaters and the controls was significant on antisocial, psychotic
      thinking and psychotic delusion scales, although scores on clinical syndromes
      were low for both cases and controls. Discriminant analysis showed that
      antisocial personality was predictive for STD repeaters. CONCLUSIONS: This study
      support the hypothesis that STD repeaters are different from controls in terms of
      their psychological characteristics. The behaviour of STD repeaters is ego
      syntonic, which makes the treatment of their personality difficult and emphasizes
      the importance of work on primary and secondary prevention of STD.

PMID- 11952294
TI  - Serum iron, ferritin, folic acid, and vitamin B12 levels in recurrent aphthous
      stomatitis.
AB  - BACKGROUND: The exact aetiology of recurrent aphthous stomatitis (RAS) is still
      unknown, but different predisposing factors, including iron, vitamin B12 and
      folic acid deficiencies, have been proposed. MATERIAL AND METHODS: Serum iron,
      ferritin, folic acid and vitamin B12 levels were investigated in 35 patients with
      RAS and in 26 healthy controls. RESULTS: Vitamin B12 levels were found
      significantly lower in subjects with RAS than in controls. No significant
      differences were found in other parameters. CONCLUSION: We concluded that vitamin
      B 12 deficiency may be an aetiological factor in recurrent aphthous stomatitis.

PMID- 11952295
TI  - Increased incidence of pemphigus vulgaris in southern Europeans living in Germany
      compared with native Germans.
AB  - BACKGROUND: The two major subtypes of pemphigus include: pemphigus vulgaris (PV)
      and pemphigus foliaceus. Only limited data are available on the epidemiology of
      these diseases. OBJECTIVE: The aim of the present study was to estimate the
      gender- and age-specific incidences of PV in two well-defined regions of Germany
      and to compare the incidences among native Germans with those in citizens from
      other countries living in Germany. METHODS: We performed a retrospective review
      of records from all patients that were diagnosed with PV at the Departments of
      Dermatology in Wurzburg and Mannheim between 1989 and 1997. RESULTS: During the
      observation period, 14 patients were diagnosed with PV coming from an area with
      1.46 million residents. With regard to the patients' age, the highest incidence
      for women was found in the 51-65-year-old-age group with 2.34 [95% confidence
      interval (CI): 0.36; 7.76] new cases per 1 million inhabitants per year. The
      highest incidence for men was observed in the over 65-year-old age group with
      3.72 (95% CI: 0.95; 9.8) cases/million peryear. In the 51-65-year-old age
      group,we found a 25-foldhigher incidence of PV in foreigners living in Germany
      compared with native Germans. The age-adjusted incidence of PV was ninefold
      higher in foreigners compared with native Germans. Interestingly, all non-German
      patients came from two southern European countries (Turkey and Italy).
      CONCLUSIONS: The age-adjusted incidence of PV differs between native Germans and
      foreigners living in Germany. Further studies are necessary to address the risk
      factors (genetic and/or environmental) that contribute to this difference.

PMID- 11952296
TI  - Urethral caruncle in a male: a case report.
AB  - Urethral caruncle in a 60-year-old male labourer is being reported. Its
      occurrence in male urethra has not been reported so far in the literature.

PMID- 11952297
TI  - Rheumatoid neutrophilic dermatitis: an initial dermatological manifestation of
      seronegative rheumatoid arthritis.
AB  - Rheumatoid neutrophilic dermatitis (RND) is an uncommon, but distinctive
      manifestation of rheumatoid arthritis (RA). We describe the case of a 35-year-old
      female who developed RND as an early stage of seronegative RA. Clinically, the
      lesions were presented by erythematous, slightly tender, papules, 5-10 mm in
      diameter, on the extensor surface of the left arm. The histopathological findings
      revealed a dense, dermal, mainly neutrophilic infiltrate, with prominent
      leucocytoclasia, but without any features of vasculitis. There was fibrinoid
      degeneration of collagen, resembling the collagen changes present in rheumatoid
      nodules in a miniaturized form. RND can be a reliable, early clinical sign of RA,
      as seen in our patient. Furthermore, this case demonstrates that RND may be
      associated not only with seropositive RA, as described in the literature, but
      also with seronegative RA, never before reported. The histological findings in
      our case are remarkable because of the fibrinoid collagen degeneration, which is
      described here for the first time in RND. Thus, RND may, in fact, be the initial
      phase of a spectrum that begins with a neutrophilic reaction and mild fibrinoid
      collagen degeneration, and evolves into rheumatoid nodules at the final stage.

PMID- 11952298
TI  - Epidermolysis bullosa acquisita: treatment with intravenous immunoglobulins.
AB  - Epidermolysis bullosa acquisita (EBA) is a rare autoimmune bullous disorder that
      is often difficult to treat. Few cases have been reported and therapy consists
      mainly of combinations of systemic steroids, immunosuppressants and, recently,
      administration of intravenous human immunoglobulin (IVIg). We describe a case of
      EBA in which our therapeutic choices were limited due to the patient's poor
      general condition, including extensive infection of the lesions and a history of
      pulmonary tuberculosis. The patient was treated with IVIg at a dose of 400 mg/kg
      per day for 5 consecutive days every 4 weeks. The treatment was well tolerated
      and the results were satisfactory. It seems that IVIg, due to its possible
      immunomodulatory mode of action, can be an efficacious therapeutic agent in this
      rare autoimmune disease.

PMID- 11952299
TI  - Furosemide-induced bullous pemphigoid.

PMID- 11952300
TI  - Spontaneous regression in primary cutaneous neuroendocrine (Merkel cell)
      carcinoma: a rare immune phenomenon?

PMID- 11952301
TI  - Linear IgA bullous dermatosis in a patient with sclerosing cholangitis.

PMID- 11952302
TI  - Umbilical metastasis from ovarian carcinoma: Sister Mary Joseph's nodule.

PMID- 11952303
TI  - Pityriasis versicolor resembling pityriasis rotunda.

PMID- 11952304
TI  - Efficacy and tolerability of terbinafine 1% emulsion gel in patients with tinea
      pedis.

PMID- 11952305
TI  - Dermatitis herpetiformis and gluten-sensitive enteropathy in a patient with
      nodular prurigo.

PMID- 11952306
TI  - Calcitriol treatment of glucocorticoid-induced osteoporosis in subjects with
      pemphigus vulgaris.

PMID- 11952307
TI  - Toxic epidermal necrolysis in a patient infected with human immunodeficiency
      virus-2.

PMID- 11952308
TI  - Leishmaniasis of the prepuce.

PMID- 11952309
TI  - Advances in ultrasound.
AB  - Ultrasound (US) has undergone dramatic changes since its inception three decades
      ago; the original cumbersome B-mode gantry system has evolved into a high
      resolution real-time imaging system. This review describes both recent advances
      in ultrasound and contrast media and likely future developments. Technological
      advances in electronics and computing have revolutionized ultrasound practice
      with ever expanding applications. Developments in transducer materials and array
      designs have resulted in greater bandwidths with improvements in spatial and
      contrast resolution. Developments in digital signal processing have produced
      innovations in beam forming, image display and archiving. Technological advances
      have resulted in novel imaging modes which exploit the non-linear behaviour of
      tissue and microbubble contrast agents. Microbubble contrast agents have
      dramatically extended the clinical and research applications of ultrasound. Not
      only can Doppler studies be enhanced but also novel non-linear modes allow
      vessels down to the level of the microcirculation to be imaged. Functional and
      quantitative studies allow interrogation of a wide spectrum of tissue beds. The
      advent of tissue-specific agents promises to improve the sensitivity and
      specificity of ultrasound in the detection and characterization of focal liver
      lesions to rival that of computed tomography (CT) and magnetic resonance imaging
      (MRI). Ultrasound has recently moved into therapeutic applications with high
      intensity focused ultrasound (HIFU) and microbubble assisted delivery of drugs
      and genes showing great promise.

PMID- 11952310
TI  - Establishing a contract for a PACS managed service.
AB  - This review considers the process of contracting for a picture archiving and
      communication system (PACS) using the private finance initiative (PFI) managed
      service route. The PFI process is reviewed and the advantages and disadvantages
      of a managed service detailed. During contract negotiations several areas of
      conflict were encountered. These are discussed with an outline of how they were
      resolved. CONCLUSION: A contract for a PACS has been achieved by a large acute
      hospital Trust using a managed service provision through PFI. In detailing the
      specific problems encountered in the course of negotiations, it is intended that
      other Trusts entering on this course will be equipped and strengthened in the
      finalizing of satisfactory and robust contracts.

PMID- 11952311
TI  - Detection of colorectal carcinoma on double contrast barium enema when double
      reporting is routinely performed: an audit of current practice.
AB  - PURPOSE: To determine the sensitivity of double contrast barium enema (DCBE) in
      the detection of colorectal carcinoma (CRC) when double reporting is routinely
      performed. METHOD AND MATERIALS: Over a 1-year period all patients with a
      diagnosis of CRC within a large teaching hospital were identified. Using computer
      records, any patient with CRC who had had a DCBE within 5 years of diagnosis was
      identified. During this time period all DCBE were double reported by the
      radiographer or radiology trainee who performed the enema and by a consultant
      radiologist specializing in gastrointestinal radiology. RESULTS: Over the 1-year
      period 169 patients were identified with a diagnosis of CRC. Seventy patients had
      had a DCBE within the preceding 5 years. Sixty-four patients had had CRC
      diagnosed on the DCBE. One patient had a sessile polyp diagnosed, which was
      removed at colonoscopy and found to be an invasive adenocarcinoma. In five cases
      (7%) the CRC was not diagnosed on DCBE. In three cases the lesions could be seen
      retrospectively, in one case the lesion could not be seen and in one case the
      examination had been incomplete. CONCLUSION: In our series the miss-rate for CRC
      was 7%. Previous studies have shown miss-rates of 15-24%. These studies have not
      routinely employed double reporting. Our results suggest that double reporting of
      DCBE significantly reduces the miss-rate and that this reduction is due to fewer
      perceptive errors.

PMID- 11952312
TI  - CT fluoroscopy-assisted puncture of thoracic and abdominal masses: a randomized
      trial.
AB  - PURPOSE: We investigated the benefit of real-time guidance of interventional
      punctures by means of computed tomography fluoroscopy (CTF) compared with the
      conventional sequential acquisition guidance. MATERIAL AND METHODS: In a
      prospective randomized trial, 75 patients underwent either CTF-guided (group A, n
      = 50) or sequential CT-guided (group B, n = 25) punctures of thoracic (n = 29) or
      abdominal (n = 46) masses. CTF was performed on the CT machine (Somatom Plus 4
      Power, Siemens Corp., Forchheim, Germany) equipped with the C.A.R.E. Vision
      application (tube voltage 120 kV, tube current 50 mA, rotational time 0.75 s,
      slice thickness 10 mm, 8 frames/s). RESULTS: The average procedure time showed a
      statistically significant difference between the two study groups (group A: 564
      s, group B 795 s, P = 0.0032). The mean total mAs was 7089 mAs for the CTF and
      4856 mAs for the sequential image-guided intervention, respectively. The
      sensitivity was 71% specificity 100% positive predictive value 100% and negative
      predictive value 60% for the CTF-guided puncture, and 68, 100, 100 and 50% for
      sequential CT, respectively. CONCLUSION: CTF guidance realizes a time-saving but
      increases the radiation exposure dosage.

PMID- 11952313
TI  - MR evaluation of normal retroperitoneal and pelvic lymph nodes.
AB  - PURPOSE: To establish guidelines for normal retroperitoneal and pelvic lymph node
      size at magnetic resonance imaging (MRI) by correlation with computed tomographic
      (CT) and lymphangiographic (LAG) data. MATERIALS AND METHODS: Twelve patients
      previously studied with pre- and post-LAG CT to determine normal pelvic lymph
      node size [ 1 ] were examined with MRI. All were on surveillance for stage I
      testicular tumour (minimum follow-up 10 years). Three observers recorded blind
      the site, size and number of nodes in the retroperitoneum and pelvis at 11 sites.
      The results were validated with previous CT imaging. RESULTS: Eight hundred and
      fifteen nodes in 12 patients were visible on the MRI initially, and a further 44
      nodes were identified after comparison with post-LAG CT. More nodes were seen on
      MRI than on CT. The 95th centile values for maximum short axis diameter (MSAD) of
      pelvic lymph nodes were common iliac and obturator 4 mm, external and internal
      iliac 5 mm and hypogastric 6 mm. In the retroperitoneum the 95th centile MSAD
      values were retrocrural, high left para-aortic, paracaval and interaortocaval 3
      mm, post-caval 4 mm and low left para-aortic 5 mm. CONCLUSION: MRI criteria for
      normal retroperitoneal and pelvic lymph node size are defined. Adoption of these
      recommendations may improve the sensitivity of MRI for the detection of nodal
      metastases.

PMID- 11952314
TI  - Invited commentary. MR evaluation of normal retroperitoneal and pelvic lymph
      nodes.

PMID- 11952316
TI  - CT and MR features of nasopharyngeal carcinoma in children and young adults.
AB  - AIM: To clarify CT and MR features of nasopharyngeal carcinoma (NPC) in children
      and young adults. METHOD: CT and MR findings of 13 patients (30 years old or
      younger) with a histopathologic diagnosis of NPC were reviewed. RESULTS: Skull
      base invasion (12/13), lymphadenopathy (10/13), and infiltrative growth (8/8)
      were common findings. The signal intensity of tumours was slightly higher than
      that of muscles in six cases and isointense to that of muscles in two cases on T1
      weighted images; it was higher than that of muscle and lower than that of
      cerebellar grey matter on T2-weighted images in all cases. Internal signals were
      homogeneous in both pre- and post-Gd-enhanced MR images in all cases.
      CONCLUSIONS: Despite its rarity in this age group, NPC should be included in a
      differential diagnosis when CT and MR imaging reveal these features.

PMID- 11952317
TI  - MR imaging and computed tomography in patients with rectal tumours clinically
      judged as locally advanced.
AB  - AIM: To compare magnetic resonance (MR) imaging and computed tomography (CT) in
      the local staging of locally advanced rectal tumours. MATERIALS AND METHODS:
      Sixteen consecutive patients who, after pre-operative radio-chemotherapy (RCT),
      had surgery for rectal tumours clinically judged as extending into neighbouring
      tissues in the pelvis, were examined using MR and CT before and after treatment.
      The examinations were reviewed by four radiologists. The relation of the tumours
      to 14 different anatomic structures in the pelvis in a total of 50 examinations
      was studied. The results were compared to surgical and histopathological
      findings. RESULTS: Seven patients had tumour infiltration of adjacent organs in
      the pelvis at surgery, the most common being the urinary bladder, prostate,
      uterus and small bowel. MR predicted involvement of the urinary bladder and the
      uterus better than CT. However, there were more false positive findings on MR
      than on CT compared to surgical and histopathological findings. CONCLUSION: For
      staging of advanced rectal cancers, the overall results were not significantly
      better for MR than CT. If involvement of the urinary bladder and the uterus
      cannot be ruled out using CT, MR is advocated due to its higher soft tissue
      contrast resolution and multi-planar capability.

PMID- 11952318
TI  - Diffusion MR imaging in glioma: does it have any role in the pre-operation
      determination of grading of glioma?
AB  - AIM: To investigate the role of the diffusion MR weighted sequence in the pre
      operative grading of gliomas, and its application in defining the different
      components of these tumours. MATERIALS AND METHODS: Seventeen patients with
      gliomas (eight high grade, nine low grade) had diffusion weighted imaging.
      Apparent diffusion coefficients (ADCs) of different components of tumours were
      measured. RESULTS: ADC of the cystic portion of the tumour was significantly
      higher than ADCs of the enhanced tumour, non-enhanced tumour and perifocal oedema
      (P < 0.01). No significant difference in ADC values between low grade and high
      grade glioma (P > 0.7) was found nor was there any difference between oligoglioma
      and non-oligoglioma (P > 0.29). CONCLUSION: ADC value was useful to differentiate
      the cystic from the solid components of the tumours. However, it was not useful
      in pre-operative grading of glioma.

PMID- 11952319
TI  - Case report: hepatic and retro-peritoneal endometriosis presenting as obstructive
      jaundice with ascites: a case report and review of the literature.

PMID- 11952320
TI  - 'Leafy' pattern in phyllodes tumour of the breast: MRI-pathologic correlation.

PMID- 11952321
TI  - Diagnostic and therapeutic impact of MRI.

PMID- 11952322
TI  - Comparison of Doppler ultrasound, magnetic resonance angiographic techniques and
      catheter angiography in evaluation of carotid stenosis.

PMID- 11952323
TI  - Comparison of Doppler ultrasound, magnetic resonance angiographic techniques and
      catheter angiography in evaluation of carotid stenosis.

PMID- 11952324
TI  - Applying 'technology assessment' and 'evidence-based medicine' theory to
      interventional radiology. Part one: suggestions for the phased evaluation of new
      procedures.

PMID- 11952325
TI  - Internal carotid aneurysm presenting as hypoglossal and glossopharyngeal nerve
      palsy.

PMID- 11952326
TI  - CT in urinary tract trauma.

PMID- 11952327
TI  - Interaction of intra-articular steroids and bupropion.

PMID- 11952328
TI  - Error review: can this improve reporting performance.

PMID- 11952329
TI  - Use of impact factors.

PMID- 11952331
TI  - Microsome-mediated oxidation of N-nitrosodiethanolamine (NDELA), a bident
      carcinogen.
AB  - N-Nitrosodiethanolamine (NDELA), an environmentally prevalent, potent carcinogen,
      undergoes competitive rat liver microsome-mediated oxidation at both the alpha
      (adjacent to N)- and beta-positions of the 2-hydroxyethyl chains. The former
      process, alpha-hydroxylation, is detected by the formation of glycolaldehyde
      (determined as its 2,4-dinitrophenylhydrazone DNP) that is assumed to arise from
      the decomposition of the corresponding alpha-hydroxynitrosamine, which is also
      the progenitor of the 2-hydroxyethyldiazonium ion. This finding refutes prior
      published work that states that the alpha-hydroxylation of NDELA does not occur.
      Competitive microsomal oxidation at the beta-position gives the hemiacetal N
      nitroso-2-hydroxymorpholine (NHMOR) at a rate 1.5 times alpha-hydroxylation.
      Glycolaldehyde is oxidized in this system to glyoxal at a rate 39 times the
      conversion of NDELA to glycolaldehyde. The alpha-hydroxylation of NHMOR at either
      C-3 or C-5 to give glyoxal or glycolaldehyde, respectively, occurs at respective
      rates 3-6 times that of the alpha-hydroxylation of NDELA. Ethylene glycol, a
      hydrolysis product of the 2-hydroxyethyldiazonium ion is shown to undergo
      microsome mediate oxidation to glyoxal. Ethyl-2-hydroxyethylnitrosamine (NEELA)
      undergoes a similar set of microsome-mediated oxidations at alpha-position of the
      ethyl (fastest) and 2-hydroxyethyl groups, as well as beta-oxidation of the 2
      hydroxyethyl group, a process which is slightly more rapid than alpha
      hydroxylation of the same chain. Comparisons of oxidations rates of these
      substrates, as manipulated by preinducers, isoniazid, streptozocin, and
      phenobarbital, and enzyme inhibitors diethyldithiocarbamate and 4-methylpyrazole,
      with that of dimethylnitrosamine, a substrate for cytochrome P450 2E1, strongly
      suggest that this isozyme is also responsible for the oxidations reported here.
      alpha-Deuteration of NDELA practically eliminates its alpha-hydroxylation by
      microsomes from isoniazid induced rats, but doubles beta-oxidation, while beta
      deuteration of this substrate significantly reduces beta-oxidation and enhances
      alpha-hydroxylation. Since both glyoxal-guanine and 2-hydroxyethyl-DNA base
      adducts are known to arise from the in vivo administration of NDELA and because
      this work demonstrates that these two fragments can come from the microsomal
      oxidation of a single nitrosamine molecule containing the 2-hydroxyethyl group,
      NDELA and related nitrosamines are bident (two-toothed) carcinogens, a process
      which is likely to enhance their carcinogenic potency.

PMID- 11952332
TI  - DNA adducts from N-nitrosodiethanolamine and related beta-oxidized nitrosamines
      in vivo: (32)P-postlabeling methods for glyoxal- and O(6)
      hydroxyethyldeoxyguanosine adducts.
AB  - The mechanism by which environmentally prevalent N-nitrosodiethanolamine (NDELA)
      and related 2-hydroxyethyl- or other beta-oxidized nitrosamines initiate the
      carcinogenic process has remained obscure. (32)P-Postlabeling assays for the pH
      sensitive glyoxal-deoxyguanosine (gdG) and the O(6)-2-hydroxyethyldeoxyguanosine
      (OHEdG) DNA adducts have been developed as probes in this mechanistic
      investigation and used in both in vitro and in vivo experiments. The ready
      cleavage of the glyoxal fragment from gdG at pH 7 and greater has required
      methods of optimization in order to achieve a detection limit of 0.05
      micromol/mol of DNA. Nuclease P1 treatment enhances the detection of gdG adducts
      but does not increase the detection limit for OHEdG. For OHEdG, best results were
      achieved using fraction collection from HPLC (0.3 micromol/mol of DNA). Using
      radiochemical methods, both adducts could be detected either by HPLC or 2D TLC.
      NDELA, N-nitrosomorpholine (NMOR), N-nitrosomethyethanolamine (NMELA), and N
      nitrosoethylethanolamine (NEELA) all produce both gdG and OHEdG adducts in rat
      liver DNA in vivo and are called bident carcinogens because fragments from both
      chains of the nitrosamine are incorporated into DNA. N-Nitroso-2
      hydroxymorpholine (NHMOR), a metabolite of NDELA and NMOR, generates gdG in DNA
      in vitro and in vivo. gdG DNA adducts were found in the range 1.1-6.5
      micromol/mol of DNA. OHEdG DNA adducts were produced from equimolar amounts of
      nitrosamines in rat liver in vivo over the range 4-25 micromol/mol of DNA and in
      the order NMELA > NEELA > NDELA > NMOR. Deuterated isotopomers of NDELA showed a
      marked isotope effect on DNA OHEdG adduct formation. alpha-Deuteration markedly
      decreased OHEdG adduct formation while beta-deuteration had the opposite effect.
      These data support the hypothesis that NDELA and related nitrosamines are
      activated by both enzyme mediated alpha-hydroxylation and beta-oxidation. The
      formation of OHEdG adducts from NDELA requires alpha-hydroxylation of the 2
      hydroxyethyl chain, and formation of gdG necessitates a beta-oxidation as well.
      The bident nature of these carcinogens may explain why they are relatively potent
      carcinogens despite the fact that major proportions of doses are excreted
      unchanged.

PMID- 11952333
TI  - Oxidation of proximal protein sulfhydryls by phenanthraquinone, a component of
      diesel exhaust particles.
AB  - Diesel exhaust particles (DEP) contain quinones that are capable of catalyzing
      the generation of reactive oxygen species in biological systems, resulting in
      induction of oxidative stress. In the present study, we explored sulfhydryl
      oxidation by phenanthraquinone, a component of DEP, using thiol compounds and
      protein preparations. Phenanthraquinone reacted readily with dithiol compounds
      such as dithiothreitol (DTT), 2,3-dimercapto-1-propanol (BAL), and 2,3-dimercapto
      1-propanesulfonic acid (DMPS), resulting in modification of the thiol groups,
      whereas minimal reactivities of this quinone with monothiol compounds such as
      GSH, 2-mercaptoethanol, and N-acetyl-L-cysteine were seen. The modification of
      DTT dithiol caused by phenanthraquinone proceeded under anaerobic conditions but
      was accelerated by molecular oxygen. Phenanthraquinone was also capable of
      modifying thiol groups in pulmonary microsomes from rats and total membrane
      preparation isolated from bovine aortic endothelial cells (BAEC), but not bovine
      serum albumin (BSA), which has a Cys34 as a reactive monothiol group. A
      comparison of the thiol alkylating agent N-ethylmaleimide (NEM) with that of
      phenanthraquinone indicates that the two mechanisms of thiol modification are
      distinct. Studies revealed that thiyl radical intermediates and reactive oxygen
      species were generated during interaction of phenanthraquinone with DTT. From
      these findings, it is suggested that phenanthraquinone-mediated destruction of
      protein sulfhydryls appears to involve the oxidation of presumably proximal
      thiols and the reduction of molecular oxygen.

PMID- 11952334
TI  - Effect of liquid depth on the synthesis and oxidation of nitric oxide in
      macrophage cultures.
AB  - The effect of liquid depth on the synthesis of NO and O(2)(-) was studied in
      murine macrophage-like RAW 264.7 cells activated by bacterial lipopolysaccharide
      and interferon-gamma. Rates of NO(2)(-) and NO(3)(-) accumulation were determined
      8-11 h after stimulation. The rate of NO synthesis was computed by using a
      reaction-diffusion model to correct NO(2)(-) and NO(3)(-) accumulation for
      physical loss of NO, whereas O(2)(-) synthesis was equated with NO(3)(-)
      formation. Rates of O(2)(-) synthesis determined by a spectrophotometric
      (cytochrome c) assay were in good agreement with those from NO(3)(-) accumulation
      and showed production of O(2)(-) to be detectable immediately, in contrast to the
      approximately 6 h time lag for NO. The assumption that NO(2)(-) and NO(3)(-) are
      stable end products of the extracellular oxidation of NO by O(2) and O(2)(-),
      respectively, was supported by the fact that NO(2)(-) and NO(3)(-) concentrations
      remained constant in the presence of unstimulated cells or stimulated cells where
      NO synthesis was inhibited. Data were obtained for media depths ranging from 1 to
      4 mm. The physical loss of NO was found to be quite significant, exceeding NO(2)(
      ) and NO(3)(-) accumulation by an order of magnitude at the smallest depth. The
      principal finding was that the rates of NO(2)(-) and NO(3)(-) accumulation each
      remained nearly constant over the 4-fold range of liquid depths. Because greater
      depths should greatly facilitate the trapping of NO as NO(2)(-), this implies
      that NO synthesis decreased markedly with increasing depth. In contrast, O(2)(-)
      synthesis remained approximately constant. Oxygen availability is likely to have
      affected NO synthesis, in that diffusional limitations will yield the lowest
      cellular O(2) concentrations when the liquid depth is greatest and NO synthesis
      is known to decrease when O(2) levels are reduced. Concentrations of NO near the
      cells were calculated to remain at approximately 1 microM for all conditions
      examined, suggesting that regulation of NO synthase activity by NO might also
      have mediated the effect of liquid depth.

PMID- 11952336
TI  - The Mechanism by which 4-hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (tempol)
      diverts peroxynitrite decomposition from nitrating to nitrosating species.
AB  - Tempol is a stable nitroxide radical that has been shown to protect laboratory
      animals from the injury associated with conditions of oxidative and nitrosoactive
      stress. Tempol's protective mechanisms against reactive oxygen species have been
      extensively studied, but its interactions with reactive nitrogen species remain
      little explored. Recently, it has been shown that tempol is a potent inhibitor of
      peroxynitrite-mediated phenol nitration while it increases phenol nitrosation by
      a complex mechanism [Carrol et al. (2000) Chem. Res. Toxicol. 13, 294]. To obtain
      further mechanistic insights, we reexamined the interaction of peroxynitrite with
      tempol in the absence and presence of carbon dioxide. Stopped-flow kinetic
      studies confirmed that tempol does not react directly with peroxynitrite but
      levels off the amount of oxygen (monitored with an oxygen electrode) and nitrite
      (monitored by chemiluminescence) produced from peroxynitrite in the presence and
      absence of carbon dioxide to about 30% and 70% of the initial oxidant
      concentration at pH 5.4, 6.4, and 7.4. Tempol inhibited phenol nitration while
      increasing the amounts of 4-nitrosophenol, that attained yields close to 30% of
      the peroxynitrite in the presence of carbon dioxide at pH 7.4. Fast-flow EPR
      experiments showed detectable changes in the instantaneous tempol concentration
      (maximum of 15%) only in the presence of carbon dioxide. Under these conditions,
      the instantaneous concentration of the carbonate radical anion was reduced by
      tempol in a concentration-dependent manner. The results indicate that tempol is
      oxidized by peroxynitrite-derived radicals (*OH and CO(3)(*-), in the absence and
      presence of carbon dioxide, respectively) to the oxoammonium cation which, in
      turn, is reduced back to tempol while oxidizing peroxynitrite to oxygen and
      nitric oxide. The latter reacts rapidly with peroxynitrite-derived nitrogen
      dioxide to produce the nitrosating species, dinitrogen trioxide. Overall, the
      results support a role for peroxynitrite and its derived radicals in the tissue
      pathology associated with inflammatory conditions.

PMID- 11952335
TI  - Sulfhydryl binding and topoisomerase inhibition by PCB metabolites.
AB  - Polychlorinated biphenyls (PCBs) are highly persistent contaminants in our
      environment. Their persistence is due to a general resistance to metabolic
      attack. Lower halogenated PCBs, however, are metabolized to mono- and dihydroxy
      compounds, and the latter may be further oxidized to quinones with the formation
      of reactive oxygen species (ROS). We have shown that PCB metabolism generates ROS
      in vitro and in cells in culture and this leads to oxidative DNA damage, like DNA
      strand breaks and 8-oxo-dG formation. In the present study, we have evaluated the
      reactivity of PCB metabolites with other nucleophiles, like glutathione (GSH), by
      assessing (1) quantitative GSH binding in vitro, (2) GSH and thiol (sulfhydryl)
      depletion in HL-60 cells, (3) the associated cytotoxicity, and (4) the inhibition
      of topoisomerase II activity in vitro. PCB quinones were found to bind GSH in
      vitro at a ratio of 1:1.5 and to deplete GSH in HL-60 cells as measured by both
      spectrophotometric and spectrofluorometric methods. By flow cytometry analysis,
      we confirmed that there was intracellular GSH depletion in HL-60 cells by PCB
      quinones and this is associated with cytotoxicity. On the other hand, the PCB
      hydroquinone metabolites did not bind GSH or other thiols within 1 h of exposure.
      However, by spectral analyses we found that the PCB hydroquinones could be
      oxidized enzymatically to the quinones, which could then bind GSH. The resulting
      hydroquinone-glutathione addition product(s) could undergo a second and third
      cycle of oxidation and GSH addition with the formation of di- and tri-GSH-PCB
      adducts. The effect of the PCB metabolites was also tested on a sulfhydryl
      containing enzyme, topoisomerase II. PCB quinones inhibited topoisomerase II
      activity while the PCB hydroquinone metabolites did not. Hence, the oxidation of
      PCB hydroquinone metabolites to quinones in cells followed by the binding of
      quinones to GSH and to protein sulfhydryl groups and the resulting oxidative
      stress may be important aspects of the toxicity of these compounds.

PMID- 11952338
TI  - Rabbit serum albumin hydrolyzes the carbamate carbaryl.
AB  - One of the main detoxification processes of the carbamate insecticides is the
      hydrolysis of the carbamic ester bond. Carboxylesterases seem to play important
      roles in the metabolization of carbamates. This study performs a biochemical
      characterization of the capabilities of rabbit serum albumin (RSA) to hydrolyze
      the carbamate carbaryl. Rabbit serum albumin was able to hydrolyze carbaryl with
      a K(cat) of 7.1 x 10(-5) s(-1). The K(m) for this hydrolysis reaction was 240
      microM. Human, chicken, and bovine serum albumins were also able to hydrolyze
      carbaryl. The divalent cation Cu(2+) at 1 mM concentration inhibited around 50%
      of the hydrolysis of carbaryl by RSA. Other mono- and divalent cations at 1 mM
      concentration and 5 mM EDTA exerted no significant effects on the hydrolysis of
      carbaryl by RSA. The inhibition of the carbaryl hydrolysis by sulfydril blocking
      agents suggests that a cysteine residue plays an important role in the active
      center of the catalytic activity. Both caprylic and palmitic acids were
      noncompetitive inhibitors of the carbaryl hydrolysis by RSA. The carboxyl ester p
      nitrophenyl butyrate is a substrate of RSA and competitively inhibited the
      hydrolysis of carbaryl by this protein, suggesting that the hydrolysis of
      carbaryl and the hydrolysis of carboxyl esters occur in the same catalytic site
      and through a similar mechanism. This mechanism might be based on the
      carbamylation of a tyrosine residue of the RSA. Serum albumin is a protein
      universally present in nontarget species of insecticides; therefore, the
      capability of this protein to hydrolyze other carbamates must be studied because
      it might have important toxicological and ecotoxicological implications.

PMID- 11952337
TI  - Oxidative DNA damage induced by equine estrogen metabolites: role of estrogen
      receptor alpha.
AB  - Excessive exposure to synthetic and endogenous estrogens has been associated with
      the development of cancer in several tissues. 4-Hydroxyequilenin (4-OHEN), a
      major metabolite of equine estrogens present in estrogen replacement
      formulations, has been shown to induce cytotoxic/carcinogenic effects. In the
      present study, we have found that 4-OHEN caused DNA damage in breast cancer
      cells, and cells that contain estrogen receptor alpha (S30) are more sensitive to
      4-OHEN-mediated DNA damage as compared to estrogen receptor negative cells (MDA
      MB-231). For example, concentration-dependent increases in 8-oxo-deoxyguanosine
      (8-oxo-dG), as measured by LC-MS-MS or by the Fpg comet assay, were only detected
      in the S30 cells, and the amount of this lesion could be enhanced by agents,
      which catalyze redox cycling (NADH) or deplete GSH (diethyl maleate). The role of
      the estrogen receptor in modulating DNA damage was further established in
      incubations with the ER antagonist tamoxifen, where decreases in 8-oxo
      deoxyguanosine were observed. Another equine estrogen metabolite, 4,17 beta
      hydroxyequilenin (4,17 beta-OHEN), was found to have the same cytotoxicity and a
      similar ability to induce reactive oxygen species (ROS), and caused the same
      oxidative DNA damage in S30 cells as compared to 4-OHEN. However, 4,17 beta-OHEN
      induced twice as much single strand DNA breaks in S30 cells compared to 4-OHEN.
      Also 4,17 beta-OHEN was more estrogenic than 4-OHEN as demonstrated by a higher
      binding affinity for ER alpha and an enhanced induction in activity of estrogen
      dependent alkaline phosphatase in Ishikawa cells. These data suggest that the
      mechanism of DNA damage induced by equine estrogen metabolites could involve
      oxidative stress and that the estrogen receptor may play a role in this process.

PMID- 11952339
TI  - Genotoxicity, mitochondrial damage, and apoptosis in human lymphoblastoid cells
      exposed to peroxynitrite generated from SIN-1.
AB  - SIN-1 (3-morpholinosydnonimine), the active metabolite of the vasodilator drug
      molsidomine, decomposes spontaneously in solution. In the presence of oxygen, NO*
      and O(2)(*-) are released, generating peroxynitrite, a potent oxidizing agent, at
      a constant rate over a 2 h period. We utilized this system to investigate
      mechanisms of peroxynitrite-induced cytotoxicity, genotoxicity, apoptosis, and
      mitochondrial damage in two human lymphoblastoid cell lines carrying either wild
      type (TK6 cells) or mutant p53 (WTK-1 cells) genes. Treatment of TK6 cells with 5
      mM SIN-1 for 1.5 h resulted in 28 +/- 6% survival 24 h later. Exposure in the
      presence of different radical scavengers significantly increased survival, as
      follows: cytochrome c, 96 +/- 3%; Tiron, 69 +/- 0%; SOD plus catalase, 83 +/- 5%;
      carboxy-PTIO, 87 +/- 3%; and uric acid, 87 +/- 2%. D-mannitol was ineffective in
      reducing lethality, as were SOD and catalase when added individually or in heat
      inactivated form. Spontaneous as well as SIN-1-induced mutant fractions (MF) in
      both HPRT and TK genes were significantly higher in WTK-1 cells than in TK6 cells
      (p < 0.05-0.01). Exposure to 2.5 mM SIN-1 induced time-dependent apoptosis in TK6
      cells, but not in WTK-1 cells. Mitochondrial membrane depolarization was also
      observed in both cell lines after SIN-1 treatment. Neutral comet assay
      demonstrated that SIN-1 treatment resulted in higher levels of DNA double-strand
      breaks in TK6 cells than in WTK-1 cells. Collectively, these data show that SIN-1
      can be used as an effective peroxynitrite generator in cell culture experiments
      under these experimental conditions, in which it induced a greater apoptotic
      response but was less potent as a mutagen in TK6 cells compared with WTK-1 cells.
      Thus, p53 status was an important determinant of SIN-1 induced mutagenesis and
      apoptosis in these two human lymphoblastoid cell lines.

PMID- 11952340
TI  - DNA adducts from nitroreduction of 2,7-dinitrofluorene, a mammary gland
      carcinogen, catalyzed by rat liver or mammary gland cytosol.
AB  - Nitrofluorenes are mutagenic and carcinogenic environmental pollutants arising
      chiefly from combustion of fossil fuels. Nitro aromatic compounds undergo
      nitroreduction to N-hydroxy arylamines that bind to DNA directly or after O
      esterification. This study analyzes the DNA binding and adducts from the in vitro
      nitroreduction of 2,7-dinitrofluorene (2,7-diNF), a potent mammary carcinogen in
      the rat. Potential adduct(s) of 2,7-diNF was (were) generated by reduction of 2
      nitroso-7-NF with ascorbate/H(+) in the presence of calf thymus DNA. The major
      adduct was characterized by HPLC/ESI/MS and (1)H NMR spectrometry as N
      (deoxyguanosin-8-yl)-2-amino-7-NF, and a minor one was determined by HPLC/ESI/MS
      to be a deoxyadenosine adduct of 2-amino-7-NF. Products from enzymatic
      nitroreduction were monitored by HPLC and DNA adduct formation by (32)P
      postlabeling. Xanthine oxidase/hypoxanthine-catalyzed nitroreduction of 2,7-diNF,
      2-nitrofluorene (2-NF), and 1-nitropyrene (1-NP) yielded the respective amines to
      similar extents (30-50%). However, the level of the major adducts ( approximately
      0.15/10(6) nucleotides) from 2-NF [N-(deoxyguanosin-8-yl)-2-aminofluorene] and
      2,7-diNF [N-(deoxyguanosin-8-yl)-2-amino-7-NF] was < or = 2% that from 1-NP. In
      the presence of acetyl CoA, nitroreduction of 2-NF catalyzed by rat liver
      cytosol/NADH yielded the same adduct at a level of 2.2/10(6) nucleotides. Liver
      or mammary gland cytosol with acetyl CoA yielded mainly N-(deoxyguanosin-8-yl)-2
      amino-7-NF from 2,7-diNF at >30 adducts/10(6) nucleotides, levels comparable to
      those from 1,6-dinitropyrene and 4- or 49-fold greater than the respective levels
      without acetyl CoA. Recovery of 2-nitroso-7-NF and 2-amino-7-NF from cytosol
      catalyzed reduction of 2,7-diNF indicated nitroreduction and an N-hydroxy
      arylamine intermediate. Likewise, the presence of 2-acetylamino-7-NF indicated
      that reactivity with acyltransferase(s) was not prevented by the nitro group at
      C7. These data are consistent with activation of 2,7-diNF via nitroreduction to
      the N-hydroxy arylamine and acetyl CoA-dependent O-acetylation of the latter to
      bind to DNA. Enzymatic nitroreduction of 2,7-diNF was greatly enhanced by 9
      oxidation. The nitroreduction of either 9-oxo-2,7-diNF or 9-hydroxy-2,7-diNF
      catalyzed by liver cytosol with acetyl CoA yielded two adducts (>2/10(6)
      nucleotides). Differences in the TLC migration of these adducts, compared to
      those from 2,7-diNF, and the lack of 2,7-diNF formation in the incubations
      suggested retention of the C9-oxidized groups. The relative ratios of the amine
      to amide from nitroreductions of 9-oxo-2,7-diNF and 2,7-diNF catalyzed by liver
      cytosol suggested that the 9-oxo group decreased reactivity with acyltransferase
      and, thus, the amount of N-acetoxy arylamine that binds to DNA. The mammary gland
      tumorigenicity of 2,7-diNF and the extent of its activation by the tumor target
      tissue shown herein suggest relevance of this environmental pollutant for breast
      cancer.

PMID- 11952342
TI  - Analysis and quantification of DNA adducts of 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline in liver of rats by liquid chromatography/electrospray tandem mass
      spectrometry.
AB  - Liquid chromatography with electrospray ionization tandem mass spectrometry
      (LC/ESI-MS/MS) was used to measure DNA adducts of the carcinogen 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx) with a microbore C-18 reversed-phase
      column. Quantification of the isomeric adducts N-(deoxyguanosin-8-yl)-2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (dG-C8-MeIQx) and 5-(deoxyguanosin-N(2)-yl)-2
      amino-3,8-dimethylimidazo[4,5-f]quinoxaline (dG-N(2)-MeIQx) was achieved using
      synthetic, isotopically labeled internal standards. The reaction of the N-acetoxy
      ester of 2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline (HONH-MeIQx) with
      calf thymus DNA (ct DNA) resulted in formation of these adducts in a ratio of 5:1
      (dG-C8-MeIQx:dG-N(2)-MeIQx). The detection limit by LC/ESI-MS/MS in the selected
      reaction monitoring (SRM) mode ([MH(+) --> MH - 116](+)) (loss of deoxyribose)
      approached 500 fg (1 fmol) of adduct standard, and 1 adduct per 10(8) DNA bases
      using 100 microg of DNA following solid-phase extraction. The SRM analysis of rat
      liver DNA 24 h after an oral dose of MeIQx (10 and 0.5 mg/kg) revealed the
      presence of isomeric dG-MeIQx adducts at levels of 3.07 +/- 0.84 and 0.45 +/-
      0.27 adducts per 10(7) bases, respectively. LC/ESI-MS/MS product ion spectra were
      acquired on both adducts from the elevated dose of MeIQx for unambiguous adduct
      identification. The contribution of dG-N(2)-MeIQx to the total adducts in vivo
      was significantly more important than that observed in vitro. dG-C8-MeIQx was the
      principal adduct formed at the 10 mg/kg dose, (dG-C8-MeIQx:dG-N(2)-MeIQx (3:2));
      however, dG-N(2)-MeIQx was the major lesion detected at the 0.5 mg/kg dose (dG-C8
      MeIQx:dG-N(2)-MeIQx 1:10). The striking differences between the relative amounts
      of dG-C8-MeIQx and dG-N(2)-MeIQx formed in vivo as a function of dose suggest
      that reactive esters of HONH-MeIQx other than N-acetoxy-MeIQx may be formed in
      vivo and react preferentially with the N(2) atom of guanine, or that dG-C8-MeIQx
      is removed at a significantly more rapid rate than dG-N(2)-MeIQx. The dG-N(2)
      MeIQx adduct, previously thought to be a minor adduct, is likely to be an
      important contributor to the genotoxic damage of MeIQx.

PMID- 11952341
TI  - Analysis of N- and O-glucuronides of 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol (NNAL) in human urine.
AB  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific lung
      carcinogen which may play an important role as a cause of lung cancer in smokers.
      NNK is extensively metabolized to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol
      (NNAL), which like NNK is a potent pulmonary carcinogen. NNAL in turn is
      glucuronidated, and both NNAL and its glucuronides are excreted in human urine.
      Previous studies have clearly demonstrated the presence in human urine of 4
      (methylnitrosamino)-1-(3-pyridyl)-1-(O-beta-D-glucopyranuronosyl)butane (NNAL-O
      Gluc), but did not exclude the presence of 4-(methylnitrosamino)-1-(3-pyridyl-N
      beta-D-glucopyranuronosyl)-1-butanolonium inner salt (NNAL-N-Gluc). In this
      study, we quantified NNAL, NNAL-N-Gluc, and NNAL-O-Gluc in the urine of smokers,
      snuff-dippers, and people who used the oral tobacco product "toombak". The
      presence of NNAL-N-Gluc in the urine of toombak users was confirmed by LC-ESI
      MS/MS. In smokers' urine, NNAL-N-Gluc, NNAL-O-Gluc, and NNAL comprised (mean +/-
      SD) 26.5 +/- 6.2, 32.1 +/- 17.6, and 41.4 +/- 16.6%, respectively, of total NNAL.
      In snuff-dippers' urine, the corresponding figures were 13.6 +/- 5.1, 46.6 +/-
      11.7, and 36.6 +/- 9.3%. NNAL-N-Gluc comprised 50 +/- 25% of total glucuronidated
      NNAL in smokers and 24 +/- 12% in snuff-dippers. This difference was significant
      (P = 0.01), suggesting that smoking induces glucuronidation of NNAL. The results
      of this study demonstrate that NNAL-N-Gluc contributes substantially to NNAL
      glucuronides in human urine. These results are important for a clearer
      understanding of mechanisms of detoxification of NNK in humans.

PMID- 11952343
TI  - Mass spectrometric characterization of human hemoglobin adducts formed in vitro
      by hexahydrophthalic anhydride.
AB  - Primary structural information of anhydride binding to endogenous proteins is of
      interest in order to determine the mechanism causing the type-I allergy seen in
      many anhydride-exposed workers. In addition, studies on specific protein adducts
      may generate new methods for biological monitoring. In this study, the binding of
      hexahydrophthalic anhydride (HHPA) to human hemoglobin (Hb) in vitro was
      investigated. The in vitro synthesized conjugates were analyzed using a hybrid
      quadrupole-time-of-flight mass spectrometer (Q-TOF) with electrospray ionization
      (ESI) to determine the number of HHPA adducts per Hb molecule. Structural
      information on the locations of the adducts was obtained through nanospray Q-TOF,
      liquid chromatography-ESI mass spectrometric analysis, and gas
      chromatography/mass spectrometric analysis of Pronase E and tryptic digests. Up
      to six adducts were found on the alpha-chain and five on the beta-chain. The HHPA
      adducts were localized to the N-terminal valine of the alpha- and beta-chains of
      Hb and to lysine residues at positions 7, 11, 16, and 40 of the alpha-chain and
      8, 17, 59, 66, and 144 of the beta-chain. These results will constitute a basis
      for studies on structure-activity relationships as well as for development of
      methods for biological monitoring of acid anhydrides.

PMID- 11952344
TI  - Applicability of a modified Edman procedure for measurement of protein adducts:
      mechanisms of formation and degradation of phenylthiohydantoins.
AB  - Adducts to N-terminal valine residues in hemoglobin (Hb) are used for monitoring
      in vivo doses of electrophiles and are quantitated by means of a modified Edman
      procedure, the "N-alkyl Edman procedure". In the reaction with pentafluorophenyl
      isothiocyanate, N-alkylated valines cyclize and detach from the protein as
      pentafluorophenylthiohydantoins (PFPTHs) much more efficiently than do
      unsubstituted N-terminal valine residues. The mechanisms of this reaction, and of
      possible degradation reactions, have been studied with model compounds using
      phenyl- and pentafluorophenyl isothiocyanate. The rapid cyclization to N
      alkylvaline-PTHs occurs as a consequence of the influence of substituents on ring
      formation. This facilitated cyclization favors a direct attack by the
      thiocarbamoyl nitrogen atom on valine-C-1, and is also observed to occur slowly
      at unsubstituted N-terminal valines. Such cyclization is favored in protic
      solvents. Under alkaline conditions and in the presence of air, hydrolytic and
      oxidative processes give rise to degradation products. The PTH derivatives of N
      alkylvaline are less apt to undergo such reactions than are the corresponding
      derivatives of unsubstituted valine. We conclude that the presence of an N
      substituent exerts a greater influence on the cyclization process than the
      structure of the amino acid or of the Edman reagent. For adducts of different
      structures, the method has broad applicability, for which the limits, however,
      are not yet explored. The knowledge from the studies is valid not only for the N
      alkyl Edman procedure, but also, to some extent, for the classical Edman
      degradation reaction. The oxidative side reaction gave rise to the invention of a
      novel synthesis route for insertion of nucleophiles at carbon-5 in
      thiohydantoins. The present investigation provides a basis for the N-alkyl Edman
      procedure, facilitating new toxicological applications.

PMID- 11952345
TI  - Retrospective detection of exposure to organophosphorus anti-cholinesterases:
      mass spectrometric analysis of phosphylated human butyrylcholinesterase.
AB  - In this paper a novel and general procedure is presented for detection of
      organophosphate-inhibited human butyrylcholinesterase (HuBuChE), which is based
      on electrospray tandem mass spectrometric analysis of phosphylated nonapeptides
      obtained after pepsin digestion of the enzyme. The utility of this method is
      exemplified by the positive analysis of serum samples from Japanese victims of
      the terrorist attack with sarin in the Tokyo subway in 1995.

PMID- 11952346
TI  - Photochemically catalyzed generation of site-specific 8-nitroguanine adducts in
      DNA by the reaction of long-lived neutral guanine radicals with nitrogen dioxide.
AB  - A novel photochemical approach is described for synthesizing site-specific 8
      nitro-2'-deoxyguanosine (8-nitro-dG) adducts DNA. The method is based on the
      bimolecular reaction of a neutral, deprotonated guanine radical [G(-H)*] in DNA
      and nitrogen dioxide (*NO(2)) radicals. This approach is illustrated using the
      single-stranded oligodeoxyribonucleotide 5'-d(CCATCGCTACC) dissolved in an
      aqueous solution of nitrite and bicarbonate anions at pH 7.5. The photochemical
      synthesis was triggered by the selective photodissociation of persulfate anions
      to yield SO(4)(*-) radical anions by either 308 nm XeCl excimer laser pulses or
      by a continuous irradiation with 290-340 nm light from a 1000 W Xe lamp. The
      sulfate radicals formed generate the CO(3)(*-) and *NO(2) radicals by one
      electron oxidation of the bicarbonate and nitrite anions. In turn, the CO(3)(*-)
      radicals site-selectively generate G(-H)* radicals in DNA that combine with
      *NO(2) to form 8-nitro-dG lesions in the oligonucleotide. The nitrated
      oligonucleotides were purified by reversed-phase HPLC techniques and are stable
      at 4 degrees C for at least 4 days, but depurinate at ambient temperatures of 23
      degrees C at pH 7 with a half-life of approximately 20 h. The nature of the
      reaction and decomposition products were studied by a combination of ESI and
      MALDI-TOF mass spectrometric techniques.

PMID- 11952348
TI  - Reviewing crystallographic data--sifting CIFs.

PMID- 11952347
TI  - Cross-linked thymine-purine base tandem lesions: synthesis, characterization, and
      measurement in gamma-irradiated isolated DNA.
AB  - 5-(Phenylthiomethyl)-2'-deoxyuridine has been recently shown to be a specific
      photolabile precursor of 5-(2'-deoxyuridilyl)methyl radical that is involved in
      the formation of tandem base lesion with vicinal guanine in oxygen-free aqueous
      solution. The thionucleoside was incorporated by either liquid or solid-phase
      phosphoramidite synthesis into dinucleoside monophosphates with a 2'
      deoxyadenosine residue as the vicinal nucleoside located either at the 3' or 5'
      extremity. UV-C irradiation of the modified dinucleoside monophosphate under
      anaerobic conditions gives rise to cross-linked thymine(CH2-C8)adenine tandem
      base lesions which were isolated and characterized by (1)H NMR and mass
      spectrometry analyses. The formation of the latter tandem lesions involved an
      intramolecular addition of the 5-(2'-deoxyuridilyl)methyl radical to the C8 of
      the adenine moiety. A sensitive and specific assay aimed at monitoring the
      formation of the four thymine(CH2-C8)purine adducts, namely d(T Delta G), d(G
      Delta T), d(T Delta A), d(A Delta T), within DNA, was designed. This was based on
      a liquid chromatography analysis coupled to tandem mass spectrometry (HPLC-MS/MS)
      detection of the dinucleoside monophosphates which were quantitatively released
      from gamma-irradiated DNA and oligodeoxyribonucleotides by enzymatic hydrolysis.
      The four lesions were detected in both single-stranded oligodeoxyribonucleotide
      and isolated DNA upon exposure to gamma-radiation in oxygen-free aqueous
      solution. It was found that the tandem guanine-thymine lesions were produced more
      efficiently than the adenine-thymine cross-links. Moreover, a significant
      sequence effect was observed. Thus, the yield of formation of the tandem lesions
      is higher when the purine base is located at the 5' position of the 5-(2'
      deoxyuridilyl)methyl radical.

PMID- 11952349
TI  - Iron pentacarbonyl as a precursor for molecule-based magnets: formation of
      Fe[TCNE](2) (T(c) = 100 K) and Fe[TCNQ](2) (T(c) = 35 K) magnets.
AB  - The reaction of tetracyanoethylene (TCNE) and 7,7,8,8-tetracyano-p-quinodimethane
      (TCNQ) with Fe(CO)(5) leads to formation of magnetically ordered materials of
      Fe[TCNE](2) (T(c) = 100 K) and Fe[TCNQ](2) (T(c) = 35 K) composition,
      respectively. In contrast, the reaction with 1,2-dichloro-5,6-dicyanobenzoquinone
      (DDQ) leads to a paramagnetic material.

PMID- 11952350
TI  - Tuning of electronic structures of quasi-one-dimensional bromo-bridged Ni(III)
      complexes with strong electron-correlation by doping of Co(III) ions, [Ni(1
      x)Co(x)(Chxn)(2)Br]Br(2).
AB  - We have succeeded in synthesizing the Ni(III) complexes doped by Co(III) ions,
      [Ni(1-x)Co(x)(chxn)(2)Br]Br(2) (x = 0, 0.043, 0.093, and 0.118) by using an
      electrochemical oxidation method. The single-crystal reflectance spectrum of x =
      0.118 shows an intense CT band about 0.5 eV, which is lower than that of
      [Ni(chxn)(2)Br]Br(2) (1.3 eV). The single-crystal electrical conductivities at
      room temperature of these compounds increase with increase of the amounts of
      doping of Co(III) ions. In the ESR spectra, peak-to-peak line widths DeltaH(pp)
      at room temperature change about 600 G in [Ni(chxn)(2)Br]Br(2) to 200 G in x =
      0.118. Such a large x dependence of DeltaH(pp) seems to be ascribed to the
      increasing contribution from the increasing Curie spins which have smaller line
      width. Therefore, we have tuned the electronic structures of quasi-one
      dimensional bromo-bridged Ni(III) complexes with strong electron correlations by
      doping of Co(III) ions.

PMID- 11952351
TI  - Heterolytic activation of hydrogen as a trigger for iridium complex promoted
      activation of carbon-fluorine bonds.
AB  - The cationic iridium(III) complex [IrCF(3)(CO)(dppe)(DIB)][BARF](2) where DIB = o
      diiodobenzene, dppe = 1,2-bis(diphenylphosphino)ethane, and BARF = B(3,5
      (CF(3))(2)C(6)H(3))(4)(-) undergoes reaction in the presence of dihydrogen to
      form [IrH(2)(CO)(2)(dppe)](+) as the major product. Through labeling studies and
      (1)H and (31)P[(1)H] NMR spectroscopies including parahydrogen measurements, it
      is shown that the reaction involves conversion of the coordinated CF(3) ligand
      into carbonyl. In this reaction sequence, the initial step is the heterolytic
      activation of dihydrogen, leading to proton generation which promotes alpha-C-F
      bond cleavage. Polarization occurs in the final [IrH(2)(CO)(2)(dppe)](+) product
      by the reaction of H(2) with the Ir(I) species [Ir(CO)(2)(dppe)](+) that is
      generated in the course of the CF(3) --> CO conversion.

PMID- 11952352
TI  - New class of ruthenium sulfide clusters: Ru(4)S(6)(PPh(3))(4),
      Ru(5)S(6)(PPh(3))(5), and Ru(6)S(8)(PPh(3))(6).
AB  - Reaction of RuCl(2)(PPh(3))(3) with S(2)(-) sources yields a family of phosphine
      containing Ru-S clusters which have been characterized crystallographically and
      by MALDI-MS. Ru(4)S(6)(PPh(3))(4) (Ru-Ru(av) = 2.94 A) has idealized T(d)()
      symmetry whereas Ru(6)S(8)(PPh(3))(6) (Ru-Ru(av) = 2.82 A) adopts the idealized
      O(h)() symmetry characteristic of Chevrel clusters. Ru(5)S(6)(PPh(3))(5) is
      formally derived by the addition of Ru(PPh(3)) to one face of
      Ru(4)S(6)(PPh(3))(4). In terms of its M-S connectivity, the Ru(5)S(6) cluster
      resembles a fragment of the FeMo cluster in nitrogenase.

PMID- 11952353
TI  - Novel chiral three-dimensional iron(III) compound exhibiting magnetic ordering at
      T(c) = 40 K.
AB  - The preparation and crystal structure determination of the iron(III) compound of
      formula [(NH(4))(2)[Fe(2)O(ox)(2)Cl(2)].2H(2)O](n) (1) (ox = oxalate dianion) are
      reported here. Complex 1 crystallizes in the orthorhombic system, space group
      Fdd2, with a = 14.956(7) A, b = 23.671(9) A, c = 9.026(4) A, and Z = 8. The
      structure of complex 1 consists of the chiral anionic three-dimensional network
      [Fe(2)O(ox)(2)Cl(2)](2-) where the iron(III) ions are connected by single oxo and
      bisbidentate oxalato groups. The metal-metal separations through these bridging
      ligands are 3.384(2) and 5.496(2) A, respectively. Ammonium cations and
      crystallization water molecules are located in the helical pseudohexagonal
      tunnels defined by iron atoms. The longest iron-iron distance in the
      pseudohexagonal tunnel is 15.778(2) A whereas the shortest one is 8.734(2) A. The
      iron atoms are hexacoordinated: a terminal chloro ligand and five oxygen atoms,
      that of the oxo group and four from two cis coordinated oxalate ligands, build a
      distorted octahedral environment around the metal atom. The Fe-O(oxo) bond
      distance [1.825(2) A] is significantly shorter than the Fe(III)-O(ox) [average
      value 2.103(4) A] and Fe(III)-Cl bond distances [2.314(2) A]. Magnetic
      susceptibility measurements of 1 in the temperature range 2.0-300 K reveal the
      occurrence of a susceptibility maximum at 195 K and a transition toward a
      magnetically ordered state in the lower temperature region with T(c) = 40 K. The
      strong antiferromagnetic coupling through the oxo bridge (J = -46.4 cm(-1), the
      Hamiltonian being H = -JS(A).S(B)) accounts for the susceptibility maximum
      whereas a weak spin canting of approximately 0.3 degrees due to the antisymmetric
      magnetic exchange within the chiral three-dimensional network is responsible for
      the magnetic ordering. The values of coercive field (H(c)) and remnant
      magnetization (M(r)) obtained from the hysteresis loop of 1 at 5 K are 4000 G and
      0.016 micro(B).

PMID- 11952354
TI  - Lithium fluoroarylamidinates: syntheses, structures, and reactions.
AB  - Lithium fluoroarylamidinates [(Ar(F)C(NSiMe(3))(2)Li)(n).xD] (Ar(F) = 4
      CF(3)C(6)H(4), n = 2, D = OEt(2), x = 1 (2a); n = 1, D = TMEDA, x = 1 (4a); Ar(F)
      = 2-FC(6)H(4), n = 2, D = OEt(2), x = 1 (2b); Ar(F) = 4-FC(6)H(4), n = 2, D =
      OEt(2), x = 2 (2c); Ar(F) = 2,6-F(2)C(6)H(3), n = 2, D = OEt(2), x = 1 (2d); n =
      2, D = 2,6-F(2)C(6)H(3)CN, x = 2 (3d); Ar(F) = C(6)F(5), n= 2, D = OEt(2), x = 1
      (2e), n = 1, D = TMEDA, x = 1 (4e); n = 1, x = 2, D = OEt(2) (5e); D = THF (6e))
      were prepared by the well-known method from LiN(SiMe(3))(2) and the corresponding
      nitrile in diethyl ether or by addition of the appropriate donor D to the
      respective diethyl ether complexes. Depending on the substituents at the aryl
      group and on the donors D, three different types of structures were confirmed by
      X-ray crystallography. Hydrolysis of 2e gave C(6)F(5)C(NSiMe(3))N(H)SiMe(3) (7e)
      and C(6)F(5)C(NH)N(H)SiMe(3) (8e). The lithium fluoroarylamidinates 2a-2d react
      with Me(3)SiCl to give the corresponding tris(trimethylsilyl)fluoroarylamidines
      Ar(F)C(NSiMe(3))N(SiMe(3))(2) (9a-9d). Attempts to prepare
      C(6)F(5)C(NSiMe(3))N(SiMe(3))(2) from 2e and Me(3)SiCl failed; however, the
      unprecedented cage [[C(6)F(5)C(NSiMe(3))(2)Li](4)LiF] (10e) in which a fluoride
      center is surrounded by a distorted trigonal bipyramid of five Li atoms was
      obtained from this reaction.

PMID- 11952355
TI  - A density functional study of oxygen activation by unsaturated complexes
      [M(bipy)(2)](2+), M = Cr and Fe.
AB  - Density functional theory is used to probe the reaction of O(2) with the
      unsaturated transition-metal fragments [M(bipy)(2)](2+), M = Cr, Fe. In both
      cases, calculations indicate that the O(2) molecule is initially trapped as an
      eta(2)-bound superoxide ion, where the unpaired electron in the out-of-plane pi
      orbital of O(2) is weakly coupled to those on the trivalent metal ion. In the
      chromium case, a cis-dioxo Cr(VI) complex is found to be significantly more
      stable than the superoxo species. The two minima are, however, separated by a
      large barrier, along with a change in spin state. For the iron analogue, the
      relative energies of the two minima are reversed, the superoxo complex being the
      global minimum. The energetics of the O(2) activation processes are consistent
      with previously reported mass spectrometric experiments, where an adduct,
      [M(bipy)(2)(O(2))](2+), was detected only for chromium.

PMID- 11952356
TI  - Weakly coordinating anions: crystallographic and NQR studies of halogen-metal
      bonding in silver, thallium, sodium, and potassium halomethanesulfonates.
AB  - 35Cl, (79,81)Br, and (127)I NQR (nuclear quadrupole resonance) spectroscopy in
      conjunction with X-ray crystallography is potentially one of the best ways of
      characterizing secondary bonding of metal cations such as Ag(+) to halogen donor
      atoms on the surfaces of very weakly coordinating anions. We have determined the
      X-ray crystal structure of Ag(O(3)SCH(2)Cl) (a = 13.241(3) A; b = 7.544(2) A; c =
      4.925(2) A; orthorhombic; space group Pnma; Z = 4) and compared it with the known
      structure of Ag(O(3)SCH(2)Br) (Charbonnier, F.; Faure, R.; Loiseleur, H. Acta
      Crystallogr., Sect. B 1978, 34, 3598-3601). The halogen atom in each is apical
      (three-coordinate), being weakly coordinated to two silver ions. (127)I NQR
      studies on Ag(O(3)SCH(2)I) show the expected NQR consequences of three
      coordination of iodine: substantially reduced NQR frequencies nu(1) and nu(2) and
      a fairly small NQR asymmetry parameter eta. The reduction of the halogen NQR
      frequency of the coordinating halogen atom in Ag(O(3)SCH(2)X) becomes more
      substantial in the series X = Cl < Br < I, indicating that the coordination to
      Ag(+) strengthens in this series, as expected from hard-soft acid-base
      principles. The numbers of electrons donated by the organic iodine atom to Ag(+)
      have been estimated; these indicate that the bonding to the cation is weak but
      not insignificant. We have not found any evidence for the bonding of these
      organohalogen atoms to another soft-acid metal ion, thallium. A scheme for
      recycling of thallium halide wastes is included.

PMID- 11952357
TI  - Direct addition of alcohols to organonitriles activated by ligation to a
      platinum(IV) center.
AB  - Treatment of trans-[PtCl(4)(RCN)(2)] (R = Me, Et) with R'OH (R' = Me, Et, n-Pr, i
      Pr, n-Bu) at 45 degrees C in all cases allowed the isolation of the trans
      [PtCl(4)[(E)-NH=C(R)OR'](2)] imino ester complexes, while the reaction between
      cis-[PtCl(4)(RCN)(2)] and the least sterically hindered alcohols (methanol and
      ethanol) results in the formation of cis-[PtCl(4)[(E)-NH=C(R)OR'](2)] (R/R' =
      Me/Me) or trans-[PtCl(4)[(E)-NH=C(Et)OR'](2)] (R' = Me, Et), the latter being
      formed via thermal isomerization (ROH, reflux, 3 h) of the initially formed
      corresponding cis isomers. The reaction between alcohols R'OH and cis
      [PtCl(4)(RCN)(2)] (R = Me, R' = Et, n-Pr, i-Pr, n-Bu; R = Et; R' = n-Pr, i-Pr, n
      Bu), exhibiting greater R/R' steric congestion, allowed the isolation of cis
      [PtCl(4)[(E)-NH=C(R)OR'][(Z)-NH=C(R)OR']] as the major products. The alcoholysis
      reactions of poorly soluble [PtCl(4)(RCN)(2)] (R = CH(2)Ph, Ph) performed under
      heterogeneous conditions, directly in the appropriate alcohol and for a prolonged
      time and, for R = Ph, with heating led to trans-[PtCl(4)[(E)-NH=C(R)OR'](2)] (R =
      CH(2)Ph, R' = Me, Et, n-Pr, i-Pr; R = Ph, R' = Me) isolated in moderate yields.
      In all of the cases, in contrast to platinum(II) systems, addition of R'OH to the
      organonitrile platinum(IV) complexes occurs under mild conditions and does not
      require a base as a catalyst. The formed isomerically pure (imino ester)Pt(IV)
      complexes can be reduced selectively, by Ph(3)P=CHCO(2)Me, to the corresponding
      isomers of (imino ester)Pt(II) species, exhibiting antitumor activity, without
      change in configuration of the imino ester ligands. Furthemore, the imino esters
      NH=C(R)OR' can be liberated from both platinum(IV) and platinum(II) complexes
      [PtCl(n)[H=C(R)OR'](2)] (n = 2, 4) by reaction with 1,2
      bis(diphenylphosphino)ethane and pyridine, respectively. All of the prepared
      compounds were characterized by elemental analyses (C, H, N), FAB mass
      spectrometry, IR, and (1)H, (13)C[(1)H], and (195)Pt (metal complexes) NMR
      spectroscopies; the E and Z configurations of the imino ester ligands in solution
      were determined by observation of the nuclear Overhauser effect. X-ray structure
      determinations were performed for trans-[PtCl(4)[(E)-NH=C(Me)OEt](2)] (2), trans
      [PtCl(4)[(E)-NH=C(Et)OEt](2)] (10), trans-[PtCl(4)[(E)-NH=C(Et)OPr-i](2)] (11),
      trans-[PtCl(4)[(E)-NH=C(Et)OPr-n](2)] (12), and cis-[PtCl(4)[(E)-NH=C(Et)OMe](2)]
      (14). Ab initio calculations have shown that the EE isomers are the most stable
      ones for both platinum(II) and platinum(IV) complexes, whereas the most stable
      configurations for the ZZ isomers are less stable than the respective EZ isomers,
      indicating an increase of the stability on moving from the ZZ to the EE
      configurations which is more pronounced for the Pt(IV) complexes than for the
      Pt(II) species.

PMID- 11952358
TI  - Electronic excited states of [Au(2)(dmpm)(3)](ClO(4))(2) (dmpm=
      bis(dimethylphosphine)methane).
AB  - We present studies of the resonance Raman and electronic luminescence spectra of
      the [Au(2)(dmpm)(3)](ClO(4))(2) (dmpm = bis(dimethylphosphine)methane) complex,
      including excitation into an intense band at 256 nm and into a weaker absorption
      system centered about approximately 300 nm. The resonance Raman spectra confirm
      the assignment of the 256 nm absorption band to a (1)(dsigma --> psigma)
      transition, a metal-metal-localized transition, in that nu(Au-Au) and overtones
      of it are strongly enhanced. A resonance Raman intensity analysis of the spectra
      associated with the 256 nm absorption band gives the ground-state and excited
      state nu(Au-Au) stretching frequencies to be 79 and 165 cm(-1), respectively, and
      the excited-state Au-Au distance is calculated to decrease by about 0.1 A from
      the ground-state value of 3.05 A. The approximately 300 nm absorption displays a
      different enhancement pattern, in that resonance-enhanced Raman bands are
      observed at 103 and 183 cm(-1) in addition to nu(Au-Au) at 79 cm(-1) The compound
      exhibits intense, long-lived luminescence (in room-temperature CH(3)CN, for
      example, tau = 0.70 micros, phi(emission) = 0.037) with a maximum at 550-600 nm
      that is not very medium-sensitive. We conclude, in agreement with an earlier
      proposal of Mason (Inorg. Chem. 1989, 28, 4366-4369), that the lowest-energy,
      luminescent excited state is not (3)(dsigma --> psigma) but instead derives from
      (3)(d(x2-y2,xy --> psigma) excitations. We compare the Au(I)-Au(I) interaction
      shown in the various transitions of the [Au(2)(dmpm)(3)](ClO(4))(2) tribridged
      compound with previous results for solvent or counterion exciplexes of
      [Au(2)(dcpm)(2)](2+) salts (J. Am. Chem. Soc. 1999, 121, 4799-4803; Angew. Chem.
      1999, 38, 2783-2785; Chem. Eur. J. 2001, 7, 4656-4664) and for planar,
      mononuclear Au(I) triphosphine complexes. It is proposed that the luminescent
      state in all of these cases is very similar in electronic nature.

PMID- 11952359
TI  - De novo structural prediction of transition metal complexes: application to
      technetium.
AB  - De novo structural prediction of transition metal complexes is investigated.
      Technetium complexes are chosen given their importance in medical imaging and
      nuclear waste remediation and for the chemical diversity they display. A new
      conformational searching algorithm (LIGB) for transition metals is described that
      allows one to search for different conformational and geometric isomers within a
      single simulation. In the preponderance of cases, both conformational searching
      techniques (LIGB and high-temperature molecular dynamics/simulated annealing)
      provide comparable results, while LIGB is superior for macrocyclic complexes. A
      genetic algorithm-optimized PM3(tm) parametrization for Tc is compared with the
      standard implementation and found to yield a significant improvement in
      predictive ability for the most prevalent Tc structural motifs. The utility of a
      coupled molecular mechanics-semiempirical quantum mechanics protocol is
      demonstrated for very rapid, efficient, and effective de novo prediction of
      transition metal complex geometries.

PMID- 11952360
TI  - Arsenic(III) halide complexes with acyclic and macrocyclic thio- and selenoether
      coligands: synthesis and structural properties.
AB  - The preparations of the new complexes [AsBr(3)[MeS(CH(2))(2)SMe]],
      [AsX(3)([9]aneS(3))] (X = Cl, Br or I; [9]aneS(3) = 1,4,7-trithiacyclononane),
      [AsCl(3)([14]aneS(4))] ([14]aneS(4) = 1,4,8,11-tetrathiacyclotetradecane),
      [AsX(3)([8]aneSe(2))] ([8]aneSe(2) = 1,5-diselenacyclooctane),
      [(AsX(3))(2)([16]aneSe(4))] ([16]aneSe(4) = 1,5,9,13-tetraselenacyclohexadecane),
      and [(AsBr(3))(2)([24]aneSe(6))] ([24]aneSe(6) = 1,5,9,13,17,21
      hexaselenacyclotetracosane) are described. These are obtained from direct
      reaction of the appropriate AsX(3) and 1 mol equiv of the thio- or selenoether
      ligand in anhydrous CH(2)Cl(2) (or thf for X = I) solution. The products have
      been characterized by microanalysis and IR and (1)H NMR spectroscopy. In solution
      they are extensively dissociated, reflecting the weak Lewis acidity of AsX(3).
      Reaction of AsX(3) with MeSe(CH(2))(2)SeMe or MeC(CH(2)EMe)(3) (E = S or Se) gave
      only oils. Treatment of PCl(3) or PBr(3) with Me(2)S, MeE(CH(2))(2)EMe, or
      [9]aneS(3) failed to give solid complexes, and there was no evidence from NMR
      spectroscopy for any adduct formation in solution. The crystal structures of the
      first series of thioether and selenoether complexes of As(III) are described:
      [AsBr(3)[MeS(CH(2))(2)SMe]], C(4)H(10)AsBr(3)S(2), a = 10.2818(6) A, b =
      7.8014(5) A, c = 14.503(1) A, beta = 102.9330(2) degrees, monoclinic, P2(1)/c, Z
      = 4; [AsI(3)[MeS(CH(2))(2)SMe]], C(4)H(10)AsI(3)S(2), a = 9.1528(1) A, b =
      11.5622(2) A, c = 12.0939(2) A, beta = 93.863(1) degrees, monoclinic, P2(1)()/n,
      Z = 4; [AsCl(3)([9]aneS(3))], C(6)H(12)AsCl(3)S(3), a = 17.520(4) A, b =
      17.520(4) A, c = 16.790(7) A, tetragonal, I4(1)cd, Z = 16;
      [AsCl(3)([14]aneS(4))], C(10)H(20)AsCl(3)S(4), a = 13.5942(2) A, b = 7.7007(1) A,
      c = 18.1270(3) A, beta = 111.1662(5) degrees, monoclinic, P2(1)()/n, Z = 4;
      [(AsCl(3))(2)([16]aneSe(4))], C(12)H(24)As(2)Cl(6)Se(4), a = 9.764(3) A, b =
      13.164(1) A, c = 10.627(2) A, beta = 114.90(1) degrees, monoclinic, P2(1)()/n, Z
      = 2; [(AsBr(3))(2)([16]aneSe(4))], C(12)H(24)As(2)Br(6)Se(4), a = 10.1220(1) A, b
      = 13.4494(2) A, c = 10.5125(2) A, beta = 113.49(2) degrees, monoclinic,
      P2(1)()/n, Z = 2. [AsBr(3)[MeS(CH(2))(2)SMe]] and [AsI(3)[MeS(CH(2))(2)SMe]]
      reveal discrete mu(2)-halo As(2)X(6) dimeric structures involving distorted
      octahedral As(III), with the dithioether ligand chelating. [AsCl(3)([9]aneS(3))]
      adopts a discrete molecular distorted octahedral geometry with the thioether
      behaving as a weakly coordinated fac-capping ligand. [AsCl(3)([14]aneS(4))] forms
      an infinite sheet involving two mu(2)-chloro ligands on each As but bridging to
      two distinct As centers. Each macrocycle coordinates to two adjacent As centers
      via one S atom, giving a cis-octahedral Cl(4)S(2) donor set at As(III). The
      structures of [(AsCl(3))(2)([16]aneSe(4))] and [(AsBr(3))(2)([16]aneSe(4))] adopt
      2-dimensional sheet structures with mu(2)-dihalo As(2)X(6) dimers cross-linked by
      mu(4)-tetraselenoether macrocycles, giving a disorted cis-X(4)Se(2) donor set at
      each As center. These species are compared with their antimony(III) and
      bismuth(III) analogues where appropriate.

PMID- 11952361
TI  - Metal complexes of tetrapodal ligands: synthesis, spectroscopic and thermal
      studies, and X-ray crystal structure studies of Na(I), Ca(II), Sr(II), and Ba(II)
      complexes of tetrapodal ligands N,N,N',N'-tetrakis(2
      hydroxypropyl)ethylenediamine and N,N,N',N'-tetrakis(2
      hydroxyethyl)ethylenediamine.
AB  - Twelve complexes 1-12 of general category [M(ligand)(anion)(x)(water)(y)], where
      ligand = N,N,N',N'-tetrakis(2-hydroxypropyl/ethyl)ethylenediamine (HPEN/HEEN),
      anion = anions of picric acid (PIC), 3,5-dinitrobenzoic acid (DNB), 2,4
      dinitrophenol (DNP), and o-nitrobenzoic acid (ONB), M = Ca(2+), Sr(2+), Ba(2+),
      or Na(+), x = 1 and 2, and y = 0-4, were synthesized. All of these complexes were
      characterized by elemental analysis, IR, (1)H and (13)C NMR, and thermal studies.
      X-ray crystal studies of these complexes 1-12, [Ca(HPEN)(H(2)O)(2)](PIC)(2).H(2)O
      (1), [Ca(HEEN)(PIC)](PIC) (2), Ba(HPEN)(PIC)(2) (3), [Na(HPEN)(PIC)](2) (4),
      Ca(HPEN)(H(2)O)(2)](DNB)(2).H(2)O (5),Ca(HEEN)(H(2)O)](DNB)(2).H(2)O (6),
      [Sr(HPEN)(H(2)O)(3)](DNB)(2) (7), [Ba(HPEN)(H(2)O)(2)](DNB)(2).H(2)O](2) (8),
      [[Ba(HEEN)(H(2)O)(2)](ONB)(2)](2) (9), [[Sr(HPEN)(H(2)O)(2)](DNP)(2)](2) (10),
      [[Ba(HPEN)(H(2)O)(2)](DNP)(2)](2) (11), and [Ca(HEEN)(DNP)](DNP) (H(2)O) (12),
      have been carried out at room temperature. Factors which influence the stability
      and the type of complex formed have been recognized as H-bonding interactions,
      presence/absence of solvent, nature of the anion, and nature of the cation. Both
      the ligands coordinate the metal ion through all the six available donor atoms.
      The complexes 1 and 5-11 have water molecules in the coordination sphere, and
      their crystal structures show that water is playing a dual character. It
      coordinates to the metal ion on one hand and strongly hydrogen bonds to the anion
      on the other. These strong hydrogen bonds stabilize the anion and decrease the
      cation-anion interactions by many times to an extent that the anions are
      completely excluded out of the coordination sphere and produce totally charge
      separated complexes. In the absence of water molecules as in 2 and 3 the number
      of hydrogen bonds is reduced considerably. In both the complexes the anions case
      interact more strongly with the metal ion to give rise to a partially charge
      separated 2 or tightly ion-paired 3 complex. High charge density Ca(2+) forms
      only monomeric complexes. It has more affinity toward stronger nucleophiles such
      as DNP and PIC with which it gives partially charge-separated eight-coordinated
      complexes. But with relatively weaker nucleophile like DNB, water replaces the
      anion and produces a seven coordinated totally charge-separated complex. Sr(2+)
      with lesser charge/radius ratio forms only charge-separated monomeric as well as
      dimeric complexes. Higher coordination number of Sr(2+) is achieved with
      coordinated water molecules which may be bridging or nonbridging in nature. All
      charge-separated complexes of the largest Ba(2+) are dimeric with bridging water
      molecules. Only one monomeric ion-paired complex was obtained with Ba(PIC)(2).
      Na(+) forms a unique dinuclear cryptand-like complex with HPEN behaving as a
      heptadentate chelating-cum-bridging ligand.

PMID- 11952362
TI  - Syntheses and characterizations of three-dimensional channel-like polymeric
      lanthanide complexes constructed by 1,2,4,5-benzenetetracarboxylic acid.
AB  - The hydrothermal reaction of YbCl(3) small middle dot6H(2)O with 1,2,4,5
      benzenetetracarboxylic dianhydride resulted in
      [[Yb((b)btec)(1/4)((d)btec)(3/6)(H(2)O)(2)](4).6H(2)O](n)() (1) (H(4)btec =
      1,2,4,5-benzenetetracarboxylic acid), and the solvothermal reaction of
      Er(NO(3))(3) small middle dot6H(2)O or TbCl(3).6H(2)O with 1,2,4,5
      benzenetetracarboxylic dianhydride in H(2)O/acetic acid gave rise to
      [[Er(2)((c)btec)(2/4)((e)btec)(2/4)((f)btec)(2/4)(H(2)O)(4)].4H(2)O](n)() (2) and
      [[Tb(H(2)btec)(2/4)((f)btec)(3/6)(H(2)O)].2H(2)O](n)() (3), respectively. Complex
      1 crystallizes in monoclinic space group C2/m with a = 20.8119(5) A, b =
      17.6174(1) A, c = 5.7252(2) A, beta = 92.324(1) degrees, and Z = 1. 1 possesses a
      three-dimensional framework consisting of eight-coordinate ytterbium centers and
      two kinds of channels along the c axis. Complex 2 crystallizes in triclinic space
      group P with a = 9.6739(5) A, b = 11.0039(5) A, c = 11.5523 A, alpha =
      104.8330(10) degrees, beta = 91.0000(10) degrees, gamma = 114.2570(10) degrees,
      and Z = 2. 2 has a three-dimensional framework comprising both eight- and nine
      coordinate erbium centers and channels along the a axis. Complex 3 crystallizes
      in monoclinic space group P2(1)/n with a = 10.7246(12) A, b = 7.1693(9) A, c =
      17.158(2) A, beta = 97.109(2) degrees, and Z = 4. 3 shows a three-dimensional
      framework containing nine-coordinate terbium centers and channels along the b
      axis. Uncoordinated water molecules occupy the channels in the three complexes.
      TGA and XRPD were determined for the three complexes, and the results illustrate
      that the framework of 1 is retained upon removal of uncoordinated and coordinated
      water molecules.

PMID- 11952363
TI  - Cationic complexes of iridium: diiodobenzene chelation, electrophilic behavior
      with olefins, and fluxionality of an Ir(I) ethylene complex.
AB  - The synthesis of a series of dicationic Ir(III) complexes is described. Reaction
      of Ir(CO)(dppe)I (dppe = 1,2-bis(diphenylphosphino)ethane)) with RI (R = CH(3)
      and CF(3)) results in formation of the Ir(III) precursors IrR(CO)(dppe)(I)(2) (R
      = CH(3) (1a) and CF(3) (1b)). Subsequent treatment with AgOTf (OTf = triflate)
      generates the bis(triflate) analogues IrR(CO)(dppe)(OTf)(2) (R = CH(3) (2a) and
      CF(3) (2b)), which undergo clean metathesis with NaBARF (BARF = B(3,5
      (CF(3))(2)C(6)H(3))(4)(-)) in the presence of 1,2-diiodobenzene (DIB) forming the
      dicationic halocarbon adducts [IrR(CO)(dppe)(DIB)][BARF](2) (R = CH(3) (3a) and
      CF(3) (3b)). Complexes 3a and 3b demonstrate facile exchange chemistry with
      acetonitrile and carbon monoxide forming complexes 4 and 5, respectively. NMR
      investigation of the mechanism reveals that the process proceeds through an
      eta(1)-diiodobenzene adduct, where labilization at the coordination site trans to
      the alkyl group occurs first. Complex 3a reacts with ethylene forming the
      cationic iridium(I) product [Ir(C(2)H(4))(2)(CO)(dppe)][BARF] (6), which
      demonstrates fluxional behavior. Variable-temperature NMR studies indicate that
      the five-coordinate complex 6 undergoes three dynamic processes corresponding to
      ethylene rotation, Berry pseudorotation, and intermolecular ethylene exchange in
      order of increasing temperature based on NMR line shape analyses used to
      determine the thermodynamic parameters for the processes. The DIB adducts 3a and
      3b were also found to promote olefin isomerization of 1-pentene, and
      polymerization/oligomerization of styrene, alpha-methylstyrene, norbornene, beta
      pinene, and isobutylene via cationic initiation.

PMID- 11952364
TI  - Organic-inorganic hybrid materials: hydrothermal syntheses and structural
      characterization of bimetallic organophosphonate oxides of the type
      Mo/Cu/O/RPO(3)(2-)/organoimine.
AB  - The hydrothermal reactions of a Cu(II) starting material, a molybdate source,
      2,2'-bipyridine or terpyridine, and the appropriate alkyldiphosphonate ligand
      yield two series of bimetallic organophosphonate hybrid materials of the general
      types [Cu(n)(bpy)(m)Mo(x)O(y)(H(2)O)(p)[O(3)P(CH(2))(n)PO(3)](z)] and
      [Cu(n)(terpy)(m)Mo(x)O(y)(H(2)O)(p)[O(3)P(CH(2))(n)PO(3)](z)]. The bipyridyl
      series includes the one-dimensional materials
      [Cu(bpy)(MoO(2))(H(2)O)(O(3)PCH(2)PO(3))] (1) and
      [[Cu(bpy)(2)][Cu(bpy)(H(2)O)](Mo(5)O(15))(O(3)PCH(2)CH(2)CH(2)CH(2)PO(3))].H(2)O
      (5.H(2)O) and the two-dimensional hybrids
      [Cu(bpy)(Mo(2)O(5))(H(2)O)(O(3)PCH(2)PO(3))].H(2)O (2.H(2)O),
      [[Cu(bpy)](2)(Mo(4)O(12))(H(2)O)(2)(O(3)PCH(2)CH(2)PO(3))].2H(2)O (3.2H(2)O), and
      [Cu(bpy)(Mo(2)O(5))(O(3)PCH(2)CH(2)CH(2)PO(3))](4). The terpyridyl series is
      represented by the one-dimensional
      [[Cu(terpy)(H(2)O)](2)(Mo(5)O(15))(O(3)PCH(2)CH(2)PO(3))].3H(2)O (7.3H(2)O) and
      the two-dimensional composite materials [Cu(terpy)(Mo(2)O(5))(O(3)PCH(2)PO(3))]
      (6) and [[Cu(terpy)](2)(Mo(5)O(15))(O(3)PCH(2)CH(2)CH(2)PO(3))] (8). The
      structures exhibit a variety of molybdate building blocks including isolated
      [MoO(6)] octahedra in 1, binuclear subunits in 2, 4, and 6, tetranuclear embedded
      clusters in 3, and the prototypical [Mo(5)O(15)(O(3)PR)(2)](4-) cluster type in
      5, 7, and 8. These latter materials exemplify the building block approach to the
      preparation of extended structures.

PMID- 11952365
TI  - Ligand influences on copper molybdate networks: the structures and magnetism of
      [Cu(3,4'-bpy)MoO(4)], [Cu(3,3'-bpy)(0.5)MoO(4)], and [Cu(4,4'
      bpy)(0.5)MoO(4)].1.5H(2)O.
AB  - The reactions of a Cu(II) salt, MoO(3), and the appropriate bipyridine ligand
      yield a series of bimetallic oxides, [Cu(3,4'-bpy)MoO(4)] (1), [Cu(3,3'
      bpy)(0.5)MoO(4)] (2), and [Cu(4,4'-bpy)(0.5)MoO(4)].1.5H(2)O (3.1.5H(2)O). The
      structures of 1-3 exhibit three-dimensional covalent frameworks, constructed from
      bimetallic oxide layers tethered by the dipodal organoimine ligands. However, the
      [CuMoO(4)] networks are quite distinct. For structure 1, the layer consists of
      corner-sharing [MoO(4)] tetrehedra and [CuN(2)O(3)] square pyramids, while the
      layer of 2 is constructed from [MoO(4)] tetrehedra and binuclear [Cu(2)O(6)N(2)]
      units of edge-sharing copper square pyramids. The oxide substructure of 3
      consists of [MoO(4)] tetrahedra corner-sharing with tetranuclear clusters of edge
      sharing [CuO(5)N] octahedra. Crystal data: C(10)H(8)N(2)O(4)CuMo (1),
      orthorhombic Pbca, a = 12.4823(6) A, b = 9.1699(4) A, c = 19.5647(9) A, V =
      2239.4(1) A(3), Z = 8; C(5)H(4)NO(4)CuMo (2), triclinic P, a = 5.439(1) A, b =
      6.814(1) A, c = 10.727(2) A, alpha = 73.909(4)(o), beta = 78.839(4)(o); gamma =
      70.389(4)(o); V = 357.6(1) A(3), Z = 2; C(10)H(8)N(2)O(8)Cu(2)Mo(2).3H(2)O
      3.1.5H(2)O, triclinic P, a = 7.4273(7) A, b = 9.2314(8) A, c = 13.880(1) A, alpha
      = 71.411(2)(o), beta = 88.528(2)(o), gamma = 73.650(2)(o), V = 863.4(1) A(3), Z =
      2. The magnetic properties of 1-3 arise solely from the presence of the Cu(II)
      sites, but reflect the structural differences within the bimetallic oxide layers.
      Compound 1 exhibits magnetic behavior consistent with ferromagnetic chains which
      couple antiferromagnetically at low temperature. Compound 2 exhibits strong
      antiferromagnetic dimeric interactions, with the magnetic susceptibility data
      consistent with the Bleaney-Bowers equation. Similarly, the magnetic
      susceptibility of 3 is dominated by antiferromagnetic interactions, which may be
      modeled as a linear S = 1/2 Heisenberg tetramer.

PMID- 11952366
TI  - Intercalated organic-inorganic perovskites stabilized by fluoroaryl-aryl
      interactions.
AB  - Crystals of several new hybrid tin(II) iodide-based perovskites, involving
      2,3,4,5,6- pentafluorophenethylammonium or phenethylammonium cation bilayers and
      intercalated aryl or perfluoroaryl molecules, were grown by slow evaporation of a
      methanol solution containing the hybrid perovskite and the intercalating species.
      The (C(6)F(5)C(2)H(4)NH(3))(2)SnI(4).(C(6)H(6)) structure was solved at -75
      degrees C in a monoclinic C2/c subcell [a = 41.089(12) A, b = 6.134(2) A, c =
      12.245(3) A, beta = 94.021(5) degrees, Z = 4] and consists of sheets of corner
      sharing distorted SnI(6) octahedra separated by bilayers of
      pentafluorophenethylammonium cations. The intercalated benzene molecules form a
      single well-ordered layer interposed between adjacent fluoroaryl cation layers.
      The corresponding hybrid with an unfluorinated organic cation and fluorinated
      intercalating molecule, (C(6)H(5)C(2)H(4)NH(3))(2)SnI(4).(C(6)F(6)), is
      isostructural [a = 40.685(4) A, b = 6.0804(6) A, c = 12.163(1) A, beta =
      93.136(2) degrees, Z = 4]. For each intercalated system, close C...C contacts
      (3.44-3.50 A) between the aromatic cation and the intercalated molecule are
      indicative of a significant face-to-face interaction, similar to that found in
      the complex C(6)H(6).C(6)F(6). Crystal growth runs with the organic cation and
      prospective intercalating molecule either both fluorinated or both unfluorinated
      did not yield stable intercalated compounds, demonstrating the significance of
      fluoroaryl-aryl interactions in the current intercalated structures. Thermal
      analysis of (C(6)F(5)C(2)H(4)NH(3))(2)SnI(4).(C(6)H(6)) and
      (C(6)H(5)C(2)H(4)NH(3))(2)SnI(4).(C(6)F(6)) crystals yields, in addition to the
      characteristic transitions of the parent perovskite, endothermic transitions
      [12.6(5) and 32.1(8) kJ/mol, respectively] with an onset at 145 degrees C and a
      weight loss corresponding to the complete loss of the intercalated molecule. The
      relatively high deintercalation temperature (well above the boiling point of
      benzene and hexafluorobenzene) demonstrates the usefulness of the hybrid
      perovskites in providing a stable framework for the examination of the fluoroaryl
      aryl interaction, as well as the potential importance of this interaction in
      tailoring new hybrid perovskites. UV-vis absorption measurements on
      (C(6)H(5)C(2)H(4)NH(3))(2)SnI(4).(C(6)F(6)) thin films indicate a small
      reversible wavelength shift to higher energy for the tin(II) iodide framework
      exciton peak (with respect to that of the parent perovskite spectrum), from
      608(2) nm [2.04 eV] to 595(2) nm [2.08 eV], and a corresponding shift in the band
      edge position. This spectral shift can most reasonably be attributed to subtle
      structural changes induced in the tin(II) iodide sheets by the intercalated
      hexafluorobenzene molecules.

PMID- 11952367
TI  - Synthesis, structure, and bonding of Sc(6)MTe(2) (M = Ag, Cu, Cd): heterometal
      induced polymerization of metal chains in Sc(2)Te.
AB  - Three new compounds, Sc(6)AgTe(2), Sc(6)Cu(0.80(2))Te(2.20(2)), and Sc(6)CdTe(2),
      were prepared by high-temperature solid state techniques, and the structures were
      determined by single-crystal X-ray diffraction to be orthorhombic, Pnma (No. 62,
      Z = 4) with a = 20.094(9) A, 19.853(5) A, 20.08(1) A, b = 3.913(1) A, 3.914(1) A,
      3.915(2) A, and c = 10.688(2) A, 10.644(2) A, 10.679(5) A, respectively, at 23
      degrees C. The compounds are isotypic with Sc(6)PdTe(2) and represent the first
      ternary metal-rich rare-earth-metal chalcogenides containing group 11 or group 12
      elements. The structure can be viewed as heterometal sheets lying parallel to the
      b-c planes that are separated by isolated tellurium atoms. These sheets can also
      be viewed as a polymerization of two different types of metal chains in Sc(2)Te
      (blades and zigzag chains) by heterometal (M) replacements of some intervening
      tellurium atoms. Extended Huckel band calculations reveal that the interior atoms
      in the metal network achieve negative formal Mulliken charges while Sc atoms on
      the exterior that have tellurium neighbors have positive values. The heterometal
      metal bonding enhances the overlap populations of zigzag chains and blades
      relative to those in Sc(2)Te. The calculation results also indicate that these
      compounds are metallic, as usual.

PMID- 11952368
TI  - A hybrid consisting of coordination polymer and noncovalent organic networks: a
      highly ordered 2-D phenol network assembled by edge-to-face pi-pi interactions.
AB  - A 2-D metal-organic open framework having 1-D channels,
      [Cu(C(10)H(26)N(6))](3)[C(6)H(3)(COO)(3)](2).18H(2)O (1), was constructed by the
      self-assembly of the Cu(II) complex of hexaazamacrocycle A (A = C(10)H(26)N(6))
      with sodium 1,3,5-benzenetricarboxylate (BTC(3)(-)) in DMSO-H(2)O solution. 1
      crystallizes in the trigonal space group P with a = b = 17.705(1) A, c = 6.940(1)
      A, alpha = beta = 90 degrees, gamma = 120 degrees, V = 1884.0(3) A(3), Z = 1, and
      rho(calcd) = 1.428 g cm(-3). The X-ray crystal structure of 1 indicates that each
      Cu(II) macrocyclic unit binds two BTC(3-) ions in a trans position and each BTC(3
      ) ion coordinates three Cu(II) macrocyclic complexes to form 2-D coordination
      polymer layers with honeycomb cavities (effective size 8.1 A), and the layers are
      packed to generate 1-D channels perpendicularly to the 2-D layers. Solid 1 binds
      guest molecules such as MeOH, EtOH, and PhOH with different binding constant and
      capacity. By the treatment of 1 with aqueous solution of phenol, a hybrid solid
      [Cu(C(10)H(26)N(6))](3)[C(6)H(3)(COO)(3)](2).9PhOH.6H(2)O (2) was assembled. 2
      crystallizes in the trigonal R3 space group with a = b = 20.461(1) A, c =
      24.159(1) A, alpha = beta = 90 degrees, gamma = 120 degrees, V = 8759.2(7) A(3),
      Z = 3, and rho(calcd) = 1.280 g cm(-3). In 2, highly ordered 2-D noncovalent
      phenol layers are formed by the edge-to-face pi-pi interactions between the
      phenol molecules and are alternately packed with the coordination polymer layers
      in the crystal lattice.

PMID- 11952369
TI  - Pulse radiolysis studies on galactose oxidase.
AB  - Single-Cu-containing galactose oxidase in the GOase(semi) state (Cu(II), no
      Tyr(*) radical) reacts with pulse radiolysis generated formate radicals CO(2)(*-)
      to give an intermediate UV-vis spectrum assigned as RSSR(*-), peak at 450 nm
      (epsilon = 8100 M(-1) cm(-1)). From a detailed kinetic analysis at 450 nm, pH
      7.0, the following steps have been identified. First the strongly reducing
      CO(2)(*-) (-1.9V) reduces GOase(semi) (k(0) > or = 6.5 x 10(8) M(-1) s(-1)) to a
      species GOase(semi)(*-). This is followed by biphasic reactions (i) GOase(semi)(*
      ) + GOase(semi) (k(1) = 1.6 x 10(7) M(-1) s(-1)) to give GOase(semi) + P(*-) and
      (ii) P(*-) + GOase(semi) (k(2) = 6.7 x 10(6) M(-1) s(-1)) to give
      GOase(semi)RSSR(*-). There are no significant absorbance changes for the
      formation of GOase(semi)(*-) and P(*-), which are Cu(I) (or related) species.
      However, GOase(semi)RSSR(*-) has an absorption spectrum which differs
      significantly from that of GOase(semi). The 450 nm peak is characteristic of an
      RSSR(*-) radical with two cysteines in close sequence proximity and is here
      assigned to Cys515-Cys518, which is at the GOase surface and 10.2 A from the Cu.
      On chemical modification of the RSSR group with HSPO(3)(2-) to give RSSPO(3)H(-)
      and RS(-), absorbance changes are approximately 50% of those previously observed.
      The decay of RSSR(*-) (0.17 s(-1)) results in the formation of GOase(red). No
      RSSR(*-) formation is observed in the reaction of GOase(semi) Tyr495Phe with
      CO(2)(*-), and a single process giving GOase(red)Tyr495Phe occurs. Similarly in
      the reaction of GOase(ox) with CO(2)(*-), a single-stage reaction gives
      GOase(semi).

PMID- 11952370
TI  - Chemical bonding in hypervalent molecules: is the octet rule relevant?
AB  - The bonding in a large number of hypervalent molecules of P, As, S, Se, Te, Cl,
      and Br with the ligands F, Cl, O, CH(3), and CH(2) has been studied using the
      topological analysis of the electron localization function ELF. This function
      partitions the electron density of a molecule into core and valence basins and
      further classifies valence basins according to the number of core basins with
      which they have a contact. The number and geometry of these basins is generally
      in accord with the VSEPR model. The population of each basin can be obtained by
      integration, and so, the total population of the valence shell of an atom can be
      obtained as the sum of the populations of all the valence basins which share a
      boundary with its core basin. It was found that the population of the V(A, X)
      disynaptic basin corresponding to the bond, where A is the central atom and X the
      ligand, varies with the electronegativity of the ligand from approximately 2.0
      for a weakly electronegative ligand such as CH(3) to less than 1.0 for a ligand
      such as F. We find that the total population of the valence shell of a
      hypervalent atom may vary from close to 10 for a period 15 element and close to
      12 for a group 16 element to considerably less than 8 for an electronegative
      ligand such as F. For example, the phosphorus atom in PF(5) has a population of
      5.37 electrons in its valence shell, whereas the arsenic atom in AsMe5 has a
      population of 9.68 electrons in its valence shell. By definition, hypervalent
      atoms do not obey the Lewis octet rule. They may or may not obey a modified octet
      rule that has taken the place of the Lewis octet rule in many recent discussions
      and according to which an atom in a molecule always has fewer than 8 electrons in
      its valence shell. We show that the bonds in hypervalent molecules are very
      similar to those in corresponding nonhypervalent (Lewis octet) molecules. They
      are all polar bonds ranging from weakly to strongly polar depending on the
      electronegativity of the ligands. The term hypervalent therefore has little
      significance except to indicate that an atom in a molecule is forming more than
      four electron pair bonds.

PMID- 11952371
TI  - Structure of the deoxymyoglobin model [Fe(TPP)(2-MeHIm)] reveals unusual
      porphyrin core distortions.
AB  - The preparation and characterization of the deoxymyoglobin model (2
      methylimidazole)(tetraphenylporphinato)iron(II) is described. The preparation and
      crystallization from chlorobenzene leads to a new crystalline phase that has been
      structurally characterized. The complex is the most ordered example of a
      deoxymyoglobin model yet characterized. The X-ray structure determination reveals
      a number of distortions both in the iron coordination group and in the porphyrin
      core that result from the steric bulk of the axial ligand. Some of these
      distortions have been noted previously in related species; however, the
      demonstration of porphyrin core distortions and an asymmetry in the Fe-N(p) bond
      distances are new observations. These may have functional significance for this
      important type of heme protein coordination group. The new structure emphasizes
      that high-spin iron(II) porphyrinate derivatives display substantial structural
      pliability with significant variations in iron atom displacements, porphyrin core
      hole size, and axial and equatorial Fe-N bond lengths. The new complex has also
      been characterized by zero-field and applied field magnetic Mossbauer
      spectroscopy. Mossbauer parameters are characteristic for high-spin iron,
      although they also reveal an extremely rhombic site for iron(II). Crystal data at
      130 K for [Fe(TPP)(2-MeHIm)].1.5C(6)H(5)Cl: a = 12.334(3) A, b = 13.515(6) A, c =
      14.241(7) A, alpha = 70.62(3) degrees, beta = 88.29(2) degrees, gamma = 88.24(3)
      degrees, triclinic, space group, P, V = 2238(2) A(3), Z = 2.

PMID- 11952372
TI  - Peripherally metalated secoporphyrazines: a new generation of photoactive
      pigments.
AB  - Base-catalyzed cross condensation of dipropylmaleonitrile 1 with
      bis(dimethylamino)maleonitrile 2 in an equimolar ratio afforded the porphyrazines
      3a, 4a, 5a, 6a and 7a. Subsequent demetalation of 5a with TFA followed by
      remetalation with Zn(OAc)(2) gave ligand 5c in good yield. Compound 5c was, in
      turn, selectively oxidized and further peripherally functionalized using
      Pt(PhCN)(2)Cl(2) and PdCl(2) to yield the novel seco solitaire porphyrazines 10a
      and 10b. The photophysical profiles of the seco solitaire porphyrazines 10a and
      10b were evaluated by means of absorption, emission, and transient absorption
      spectroscopy. The new pigments 10a and 10b were found to be photochemically more
      stable than the solitaire complexes 3d and 3e and mediated the generation of
      singlet oxygen with quantum yields of 0.59 and 0.45, respectively.

PMID- 11952373
TI  - Synthesis, crystal structure, and magnetic properties of the first nonanuclear
      lanthanide(III)-copper(II) complexes of macrocyclic oxamide [NaLn(2)Cu(6)]
      (macrocyclic oxamide = 1,4,8,11-tetraazacyclotradecanne-2,3-dione, Ln = Pr, Nd).
AB  - Two new nonanuclear lanthanide(III)-copper(II) complexes of macrocyclic oxamide
      [NaPr(2)(CuL)(6)(H(2)O)(6)](ClO(4))(6)Cl small middle dot6H(2)O (1) and
      [NaNd(2)(CuL)(6)(H(2)O)(6)](ClO(4))(6)Cl small middle dot8H(2)O (2) have been
      synthesized and characterized by means of elemental analysis, IR, and electronic
      spectra, where L = 1,4,8,11-tetraazacyclotradecanne-2,3-dione. The crystal
      structures of the two complexes have been determined. The structures of 1 and 2
      consist of nonanuclear cations, perchlorate and chloride anions, and water
      molecules. In the two complexes, each copper(II) ion is connected to
      lanthanide(III) ion via the exo-cis oxygen atoms of the oxamido macrocyclic
      ligands, resulting in a tetranuclear subunit. The sodium ion links two
      tetranuclear subunits via the exo oxygen atoms of the oxamido macrocyclic ligands
      which results in a novel nonanuclear complex. The magnetic properties of the two
      complexes have been investigated. Preliminary treatment of the magnetic data by
      considering Ln(III) as free ion cannot give reasonable results, and accurate
      models involving both the orbital contribution and ligand field effect have to be
      developed.

PMID- 11952374
TI  - Theoretical investigation of the spin exchange interactions and magnetic
      properties of the homometallic ludwigite Fe(3)O(2)BO(3).
AB  - The homometallic ludwigite Fe(3)O(2)BO(3) has a complex structure made up of
      corner- and edge-sharing FeO(6) octahedra and exhibits a number of apparently
      puzzling magnetic properties. The reasons for these properties were probed by
      examining the trends in the spin exchange interactions of Fe(3)O(2)BO(3). To
      analyze the relative strengths of spin exchange interactions in such a complex
      magnetic solid, we first generalized the method of spin dimer analysis and then
      employed the resulting formulation to investigate how the magnetic properties of
      Fe(3)O(2)BO(3) are related to its reported crystal structures. The spin-orbital
      interaction energies calculated for various spin dimers of Fe(3)O(2)BO(3) provide
      estimates for the relative strengths of the associated spin exchange
      interactions, which in turn account for the observed magnetic properties of
      Fe(3)O(2)BO(3).

PMID- 11952375
TI  - Discontinuum between a thiolate and a thiol ligand.
AB  - The effect of H-bond donation to the thiolate ligand of (eta(5)
      C(5)H(5))Fe(CO)(2)SR (1) to give H-bond adducts (1 small middle dotHX) and
      eventually protonation to give [(eta(5)-C(5)H(5))Fe(CO)(2)(HSR)](+) (1H(+)()) has
      been investigated experimentally and computationally. The electronic structures
      of 1(R = Me), several derivatives of 1(R = Me) small middle dotHX, and 1(R =
      Me)H(+)() have been investigated using DFT (density functional theory)
      computational methods. As previously suggested, these calculations indicate the
      HOMO of 1 is Fedpi-Sppi antibonding and largely sulfur in character. The
      calculations indicate the electronic structure of 1 is not altered markedly by H
      bond donation to the S center, but protonation results in a reorganization of the
      electronic structure of 1H(+)() and a HOMO that is largely metal in character.
      The reduction of Fe-S distances upon protonation of 1(R = Ph) to give 1(R =
      Ph)H(+)() small middle dotBF(4)()(-)() (2.282(2) and 2.258(2) A, respectively),
      as determined by single-crystal X-ray crystallography, also indicates diminished
      Fedpi-Sppi antibonding. Using the carbonyl stretching frequencies as a gauge of
      the donor ability of the thiolate ligand, we conclude that H-bonding has a
      continuous effect on the donor properties of the thiolate ligand of 1 (i.e., is a
      function of the pK(a) of the H-bond donor). A discontinuous effect results when
      the pK(b) of 1 is reached and the complex is protonated. For our study of 1, the
      maximal effect of H-bonding is about 30% of protonation. Because the position of
      acid-base equilibrium depends on the relative basicities of the thiolate ligand
      and the conjugate base of the H-bond donor (and the relative heats of solvation
      of the acids and their conjugate bases), a true continuum of effects can be
      anticipated only for systems that are pK-matched in their given environments.
      Thus, when the conjugate base of the H-bond donor is a stronger base than the
      thiolate ligand (as in the present case), H-bond donation has a relatively small
      effect, but protonation triggers a large, discontinuous effect on the electronic
      structure of 1.

PMID- 11952377
TI  - Design and analysis of chain and network structures from organic derivatives of
      polyoxometalate clusters.
AB  - Polyoxometalate (POM) clusters derivatized with aniline groups exhibit distinct
      interactions with counterions and with each other. These interactions lead to the
      assembly of the clusters into chains and networks upon crystallization. Two
      cluster types were examined, [W(6)O(25)H(AsC(6)H(4)-4-NH(2))(2)](5-) and
      [Mo(12)O(46)(AsC(6)H(4)-4-NH(2))(4)](4-). The X-ray crystal structures were
      solved for the mixed salts containing [C(NH(2))(3)](+)/Na(+), Ag(+)/H(+), or
      Cu(2+)/H(+) as counterions. The X-ray crystal structures reveal that the POM
      clusters are linked together by hydrogen bonds or POM-metal ion-POM linkages. The
      roles of the counterions, solvents, and organic groups in the formation of
      specific crystalline architectures are discussed. Strongly interacting
      counterions form bonds to the oxo ligands of the POM and connect them into
      tetrameric units and/or into one-dimensional chains. The hydrogen bonding
      strength of the solvent influences the formation of hydrogen bonds between the
      aniline groups and oxo ligands of the cluster. The aniline groups played
      differing roles in the final structures: they were either nonbonding, bonded to a
      counterion, or involved in hydrogen bonding. Depending on the bonding
      interactions, the architecture of the cluster salts may be significantly altered.

PMID- 11952376
TI  - A bis-acetonitrile two-coordinate copper(I) complex: synthesis and
      characterization of highly soluble B(C(6)F(5))(4)(-) salts of [Cu(MeCN)(2)](+)
      and [Cu(MeCN)(4)](+).
AB  - Copper(I)-acetonitrile complexes are exceedingly useful starting materials for
      the synthesis of copper(I) complexes with polydentate ligands. To extend the
      utility of such chemistry to solution studies in relatively low-dielectric
      solvents (i.e., diethyl ether, toluene) and to aid in obtaining products amenable
      to X-ray diffraction studies, we have recently begun to employ counteranions such
      as B(C(6)F(5))(4)(-) for bioinorganic studies. Thus, the synthesis of
      [Cu(MeCN)(4)]B(C(6)F(5))(4) (1) is presented. Its recrystallization from
      CH(2)Cl(2)/pentane yields the linear, two-coordinate complex
      [Cu(MeCN)(2)]B(C(6)F(5))(4) (2), whose centrosymmetric X-ray structure shows that
      its Cu-N distance is significantly shorter than that in other two-coordinate
      Cu(I) complexes with nitrogen ligands or that in the tetrahedral complex
      [Cu(MeCN)(4)]ClO(4). Infrared spectroscopy indicates interesting and
      diagnostically useful differences between the nu(CN) of 1 and 2.

PMID- 11952378
TI  - Synthesis and structural characterization of trinuclear Cu(II)-pyrazolato
      complexes containing mu(3)-OH, mu(3)-O, and mu(3)-Cl ligands. Magnetic
      susceptibility study of [PPN](2)[(mu(3)-O)Cu(3)(mu-pz)(3)Cl(3)].
AB  - The nine-membered [-Cu(II)-N-N-](3) ring of trimeric copper-pyrazolato complexes
      provides a sturdy framework on which water is twice deprotonated in consecutive
      steps, forming mu(3)-OH and mu(3)-O species. In the presence of excess chlorides
      the mu(3)-O(H) ligand is replaced by two mu(3)-Cl ions. The interconversion of
      mu(3)-OH and mu(3)-O and the exchange of mu(3)-O(H) and mu(3)-Cl are reversible,
      and the three species involved have been structurally characterized:
      [PPN][Cu(3)(mu(3)-OH)(mu-pz)(3)Cl(3)(thf)].CH(2)Cl(2) (1a), monoclinic P2(1)/n, a
      = 10.055(2) A, b = 35.428(5) A, c = 15.153(2) A, beta = 93.802(3) degrees, V =
      5386(1) A(3), Z = 4; [Bu(4)N][Cu(3)(mu(3)-OH)(mu-pz)(3)Cl(3)] (1b), triclinic P
      1, a = 9.135(2) A, b = 13.631(2) A, c = 14.510(2) A, alpha = 67.393(2) degrees,
      beta = 87.979(2) degrees, gamma = 80.268(3) degrees, V = 1643.2(4) A(3), Z = 2;
      [PPN](2)[Cu(3)(mu(3)-O)(mu-pz)(3)Cl(3)] (2), monoclinic P2/c, a = 12.807(2) A, b
      = 13.093(2) A, c = 23.139(4) A, beta = 105.391(3) degrees, V = 3741(1) A(3), Z =
      2; [PPN](2)[Cu(3)(mu(3)-Cl)(2)(mu-pz)(3)Cl(3)].0.75H(2)O.0.5CH(2)Cl(2) (3a),
      triclinic P-1, a = 14.042(2) A, b = 23.978(4) A, c = 25.195(4) A, alpha =
      76.796(3) degrees, beta = 79.506(3) degrees, gamma = 77.629(3) degrees, V =
      7988(2) A(3), Z = 4; [Bu(4)N](2)[Cu(3)(mu(3)-Cl)(2)(mu-pz)(3)Cl(3)] (3b),
      monoclinic C2/c, a = 17.220(2) A, b = 15.606(2) A, c = 20.133(2) A, beta =
      103.057(2) degrees, V = 5270(1) A(3), Z = 4; [Et(3)NH][Cu(3)(mu(3)-OH)(mu
      pz)(3)Cl(3)(pzH)] (4), triclinic P-1, a = 11.498(2) A, b = 11.499(2) A, c =
      12.186(2) A, alpha = 66.475(3) degrees, beta = 64.279(3) degrees, gamma =
      80.183(3) degrees, V = 1331.0(5) A(3), Z = 2. Magnetic susceptibility
      measurements show that the three copper centers of 2 are strongly
      antiferromagnetically coupled with J(Cu-Cu) = -500 cm(-1).

PMID- 11952379
TI  - Synthesis, characterization, and chiral behavior of S-bridged
      Co(III)Pt(II)Co(III) trinuclear complexes composed of bis(thiolato)-type
      octahedral units cis(S)-[Co(aet)(2)(en)](+) and/or trans(N)-[Co(D-pen-
      N,O,S)(2)](-) (aet = 2-aminoethanethiolate, D-pen = D-penicillaminate).
AB  - A series of linear-type Co(III)Pt(II)Co(III) trinuclear complexes composed of
      C(2)-cis(S)-[Co(aet)(2)(en)](+) (aet = 2-aminoethanethiolate) and/or Lambda(D)
      trans(N)-[Co(D-pen-N,O,S)(2)](-) (D-pen = D-penicillaminate) were newly prepared,
      and their chiral behavior, which is markedly different from that of the
      corresponding Co(III)Pd(II)Co(III) complexes, is reported. The 1:1 reaction of an
      S-bridged Co(III)Ni(II)Co(III) trinuclear complex, [Ni[Co(aet)(2)(en)](2)]Cl(4),
      with K(2)[PtCl(4)] in water gave an S-bridged Co(III)Pt(II)Co(III) trinuclear
      complex, [Pt[Co(aet)(2)(en)](2)]Cl(4) ([1]Cl(4)), while the corresponding 1:2
      reaction produced an S-bridged Co(III)Pt(II) dinuclear complex,
      [PtCl(2)[Co(aet)(2)(en)]]Cl ([2]Cl). Complex [1](4+) formed both racemic
      (DeltaDelta/LambdaLambda) and meso (DeltaLambda) forms, which were separated and
      optically resolved by cation-exchange column chromatography. An optically active
      S-bridged Co(III)Pt(II)Co(III) trinuclear complex having the pseudo LambdaLambda
      configuration, Lambda(D)Lambda(D)-[Pt[Co(D-pen-N,O,S)(2)](2)](0)
      (Lambda(D)Lambda(D)-[3]), was also prepared by reacting Lambda(D)-trans(N)-K[Co(D
      pen-N,O,S)(2)] with K(2)[PtCl(4)] in a ratio of 2:1 in water. Treatment of the
      racemic Delta/Lambda-[2]Cl with Lambda(D)-trans(N)-K[Co(D-pen-N,O,S)(2)] in a
      ratio of 1:1 in water led to the formation of LambdaLambda(D)- and DeltaLambda(D)
      [Pt[Co(aet)(2)(en)][Co(D-pen-N,O,S)(2)]](2+) (LambdaLambda(D)- and DeltaLambda(D)
      [4](2+)) and DeltaDelta(D)-[Pt[Co(aet)(2)(en)][Co(D-pen-N,S)(2)(H(2)O)(2)]](2+)
      (DeltaDelta(D)-[4'](2+)), besides trace amounts of Lambda(D)Lambda(D)-[3] and
      DeltaDelta- and DeltaLambda-[1](4+). These Co(III)Pt(II)Co(III) complexes were
      characterized on the basis of electronic absorption, CD, and NMR spectra, along
      with single-crystal X-ray analyses for DeltaDelta/LambdaLambda-[1]Cl(4),
      DeltaLambda-[1]Cl(4), and DeltaLambda(D)-[4]Cl(2). Crystal data:
      DeltaDelta/LambdaLambda-[1]Cl(4).6H(2)O, monoclinic, space group C2/c with a =
      14.983(3) A, b = 19.857(4) A, c = 12.949(3) A, beta = 113.51(2) degrees, V =
      3532(1) A(3), Z = 4; DeltaLambda-[1]Cl(4).3H(2)O, orthorhombic, space group Pbca
      with a = 14.872(3) A, b = 14.533(3) A, c = 14.347(2) A, V = 3100(1) A(3), Z = 4;
      DeltaLambda(D)-[4]Cl(2).6H(2)O, monoclinic, space group P2(1) with a = 7.3836(2)
      A, b = 20.214(1) A, c = 10.622(2) A, beta = 91.45(1) degrees V = 1682.0(4) A(3),
      Z = 2.

PMID- 11952380
TI  - Distribution and dynamics of hydrogen in the low-temperature phase of Mg(2)NiH(4)
      studied by solid-state NMR.
AB  - Distribution and dynamics of hydrogen atoms in the low-temperature phase of
      Mg(2)NiH(4) have been studied by means of (2)H and (1)H NMR for Mg(2)NiD(4) and
      Mg(2)NiH(4), respectively. (2)H NMR spectra have been measured in the temperature
      range between 200 and 340 K, and the line shapes were simulated. The temperature
      dependence of (2)H NMR spectra was quite well simulated assuming a distorted
      tetrahedral configuration and a pseudoisotropic rotation of the NiD(4) unit. The
      estimated jump frequency obeyed Arrhenius relation with a frequency factor of
      (0.8 +/- 0.6) x 10(13) Hz and an activation energy of 50.1 +/- 1.4 kJ/mol. (1)H
      NMR spectra were acquired from 240 to 360 K. The observed (1)H second moments
      were 202 kHz(2) in the rigid lattice (240 K) and 46.6 kHz(2) in a motional state
      (360 K). The value in the rigid lattice supported the tetrahedron model, and the
      value in a motional state indicated the isotropic rotation of the NiH(4) unit.
      Conclusively, the NiH(4) unit has the distorted tetrahedral configuration and
      undergoes the pseudoisotropic rotation.

PMID- 11952381
TI  - Mononuclear and mixed-valence binuclear oxovanadium complexes with benzimidazole
      derived chelating agents.
AB  - Oxovanadium complexes with H(2)bzimpy (2,6-bis[benzimidazol-2'-yl]pyridine) and
      Me(2)bzimpy (2,6-bis[N'-methylbenzimidazol-2'-yl]pyridine), and H(3)ntb
      (tris[benzimidazol-2'-yl-methyl]amine) and Me(3)ntb (tris[N'-methylbenzimidazol
      2'-yl-methyl]amine) have been synthesized. Dioxovanadium(V) and oxovanadium(IV)
      complexes prepared from H(2)bzimpy and Me(2)bzimpy are
      [V(V)O(2)(Hbzimpy)].1.25H(2)O (1), [V(V)O(2)(Me(2)bzimpy)](ClO(4)).H(2)O (3),
      [V(IV)O(H(2)bzimpy)(H(2)O)(2)](CF(3)SO(3))(2).2H(2)O (2), and
      [V(IV)O(Me(2)bzimpy)(H(2)O)(2)](CF(3)SO(3))(2) (4). H(3)ntb and Me(3)ntb afforded
      oxovanadium(IV) complexes, [V(IV)O(Hntb)].2MeOH (5), [V(IV)O(H(3)ntb)Cl]Cl.H(2)O
      (7), [V(IV)O(Me(3)ntb)SO(4)].H(2)O (9), [V(IV)O(Me(3)ntb)Cl]Cl.H(2)O (10), and
      mixed-valence complexes, [(H(3)ntb)V(IV)O(mu
      O)V(V)O(H(3)ntb)](CF(3)SO(3))(3).2H(2)O (8) and [(Me(3)ntb)V(IV)O(mu
      O)V(V)O(Me(3)ntb)](CF(3)SO(3))(3).3H(2)O (11). Crystal structures of 2, 7, and 11
      are reported. The mixed-valence complexes, 8 and 11, show 15-line isotropic ESR
      spectra in fluid solutions at room temperature. These compounds also exhibit an
      intervalence transfer band around 1015 nm which is essentially independent of
      solvent, so these compounds are stable, mixed-valence species where the single
      unpaired electron is delocalized over the two vanadium centers at ambient
      temperature. With respect to one-electron reduction, the dioxovanadium(V)
      complexes are redox-potential equivalent with their monooxovanadium(IV)
      counterparts.

PMID- 11952382
TI  - Ru(II) electron transfer systems containing S-donor ligands.
AB  - The synthesis and properties of 3 new ligand-bridged bimetallic complexes, 1(2+),
      2(2+), and 3(2+), containing [RuCl([9]aneS(3))](+) metal centers are reported.
      Each complex was bridged by a different ditopic ligand. 1(2+) is bridged by 3,6
      bis(2-pyridyl)-1,2,4,5-tetrazine (bptz), while 2(2+) and 3(2+) are bridged by 2,3
      bis(2-pyridyl)pyrazine (dpp) and 2,2'-bipyrimidine (bpym), respectively. The
      Ru([II]) isovalent states of these complexes have been investigated using a
      variety of techniques. In the case of 3(2+), X-ray crystallography studies show
      preferential crystallization of an anti form with respect to coordinated chloride
      ligands (crystal data for [3][Cl(2)].4H(2)O: C(20)H(38)Cl(4)N(4)O(4)Ru(2)S(6),
      monoclinic, space group P2(1)/a, a = 10.929(14), b = 13.514(17), c = 11.299(16)
      A, beta = 90.52(1), V = 1669 A(3), Z = 2). UV/vis spectroscopy shows that spectra
      of these complexes are dominated by intraligand (pi-->pi) and metal-to-ligand
      Ru(d)-->L(pi) charge transfer transitions. Electrochemical studies reveal that
      metal-metal interactions are sufficiently intense to generate the Ru(III)/Ru(II)
      mixed valence [[RuCl([9]aneS(3))(2)](L-L)](3+) state, where L-L = individual
      bridging ligands. Although the 1(3+), 2(3+), and 3(3+) mixed valence states were
      EPR silent at room temperature and 77 K, isotropic solution spectra were observed
      for the electrochemically generated radical cations 1(+), 2(+), and 3(+), with
      1(+) displaying well-resolved hyperfine coupling to bridging ligand nitrogens.
      Using UV/vis/NIR spectroelectrochemistry, we investigated optical properties of
      the mixed valence complexes. All three showed intervalence charge transfer (IVCT)
      bands that are much more intense than electrochemical data indicate. Indeed, a
      comparison of IVCT data for 1(3+) with an analogous structure containing
      [(NH3)(3)Ru](2+) metal centers shows that the IVCT in the new complex is an order
      of magnitude more intense. It is concluded that although the new complexes show
      relatively weak electrostatic interactions, they possess large resonance
      energies.

PMID- 11952383
TI  - Stabilization of the P(CF(3))(2)(-) ion as a reversible CS(2) adduct,
      [P(CF(3))(2)CS(2)](-), and its potential use as a nucleophilic P(CF(3))(2)(-)
      source: synthesis and structure of [18-crown-6-K][P(C(6)F(5))(2)CS(2)].
AB  - The bis(trifluoromethyl)phosphanide ion, P(CF(3))(2)(-), decomposes slowly above 
      30 degrees C in CH(2)Cl(2) and THF solution. An increase of the thermal stability
      of the P(CF(3))(2)(-) moiety is observed if excess CS(2) is added. The
      P(CF(3))(2)(-) moiety is stabilized because of the formation of the
      bis(trifluoromethyl)phosphanodithioformate anion. Solutions of a
      [P(CF(3))(2)CS(2)](-) salt still act as a source of P(CF(3))(2)(-), even in the
      presence of excess of CS(2). The stable compound [18-crown-6-K][P(CF(3))(2)CS(2)]
      was characterized by multinuclear NMR spectroscopy, elemental analysis, and
      vibrational spectroscopy in combination with quantum chemical calculations. The
      thermally unstable P(C(6)F(5))(2)(-) ion decomposes even at -78 degrees C in
      solution giving polymeric material. The intermediate formation of the
      bis(pentafluorophenyl)phosphanide anion in the presence of excess of CS(2) allows
      the isolation of [18-crown-6-K][P(C(6)F(5))(2)CS(2)]. The novel compound
      crystallizes with one solvent molecule CH(2)Cl(2) in the monoclinic space group
      P2(1)/n with a = 1151.8(1) pm, b = 1498.1(2) pm, c = 2018.2(2) pm, beta =
      102.58(1) degrees, and Z = 4. Optimized geometric parameters of the
      [P(C(6)F(5))(2)CS(2)](-) ion at the B3PW91/6-311G(d) level of theory are in
      excellent agreement with the experimental values.

PMID- 11952384
TI  - Kinetics and mechanism of rhenium-catalyzed oxygen atom transfer from pyridine N
      oxides to phosphines.
AB  - The oxygen atom transfer (OAT) reaction cited does not occur on its own in >10 h.
      Oxorhenium(V) compounds having the formula MeReO(dithiolate)PZ(3) catalyze the
      reaction; the catalyst most studied was MeReO(mtp)PPh(3), 1, where mtpH(2) = 2
      (mercaptomethyl)thiophenol. The mechanism was studied by multiple techniques.
      Kinetics (initial-rate and full-time-course methods) established this rate law: v
      = k(c)[1][PyO](2)[PPh(3)](-1). Here and elsewhere PyO symbolizes the general case
      XC(5)H(4)NO and PicO that with X = 4-Me. For 4-picoline, k(c) = (1.50 +/- 0.05) x
      10(4) L mol(-1) s(-1) in benzene at 25.0 degrees C; the inverse phosphine
      dependence signals the need for the removal of phosphine from the coordination
      sphere of rhenium prior to the rate-controlling step (RCS). The actual entry of
      PPh(3) into the cycle occurs in a fast step later in the catalytic cycle, after
      the RCS; its relative rate constants (k(4)) were evaluated with pairwise
      combinations of phosphines. Substituent effects were studied in three ways: for
      (YC(6)H(4))(3)P, a Hammett correlation of k(c) against 3sigma gives the reaction
      constant rho(c)(P) = +1.03, consistent with phosphine predissociation; for PyO
      rho(c)(N) = -3.84. It is so highly negative because PyO enters in three steps,
      each of which is improved by a better Lewis base or nucleophile, and again for
      (YC(6)H(4))(3)P as regards the k(4) step, rho(4) = -0.70, reflecting its role as
      a nucleophile in attacking a postulated dioxorhenium(VII) intermediate. The RCS
      is represented by the breaking of the covalent N-O bond within another
      intermediate inferred from the kinetics, [MeReO(mtp)(OPy)(2)], to yield the
      dioxorhenium(VII) species [MeRe(O)(2)(mtp)(OPy)]. A close analogue,
      [MeRe(O)(2)(mtp)Pic], was identified by (1)H NMR spectroscopy at 240 K in toluene
      d(8). The role of the "second" PyO in the rate law and reaction scheme is
      attributed to its providing nucleophilic assistance to the RCS. Addition of an
      exogenous nucleophile (tetrabutylammonium bromide, Py, or Pic) caused an
      accelerating effect. When Pic was used, the rate law took on the new form v =
      k(NA)[1][PicO][Pic][PPh(3)](-1); k(NA) = 2.6 x 10(2) L mol(-1) s(-1) at 25.0
      degrees C in benzene. The ratio k(c)/k(NA) is 58, consistent with the Lewis
      basicities and nucleophilicities of PicO and Pic.

PMID- 11952385
TI  - Synthesis, structures, and emissive properties of platinum(II) complexes with a
      cyclometallating aryldiamine ligand.
AB  - A new series of square planar Pt(II) complexes with the mer-coordinating
      tridentate ligand, pip(2)NCN(-) (pip(2)NCNH = 1,3-bis(piperdylmethyl)benzene),
      has been prepared: Pt(pip(2)NCN)Cl (2), Pt(pip(2)NCN)Br (3), Pt(pip(2)NCN)I (4),
      and [Pt(pip(2)NCN)(CH(3)N=C(CH(3))(2))][CF(3)SO(3)] (5). The complexes have been
      fully characterized by (1)H NMR spectroscopy, elemental analysis, and UV-vis
      spectroscopy. The X-ray crystal structures of pip(2)NCNBr (1), 2, and 5 are
      reported. Compound 1: triclinic, P, a = 10.081(1) A, b = 10.153(2) A, c =
      10.390(1) A, alpha = 66.05(1) degrees, beta = 79.07(1) degrees, gamma = 64.51(1)
      degrees, V = 877.1(2) A(3), Z = 2. Complex 2: triclinic, P, a = 9.897(2) A, b =
      10.191(2) A, c = 19.174(4) A, alpha = 75.09(3) degrees, beta = 76.14(3) degrees,
      gamma = 71.00(3) degrees, V = 1741.2(6) A(3), Z = 4. Complex 5: triclinic, P, a =
      10.709(2) A, b = 11.2321(10) A, c = 12.447(2) A, alpha = 110.509(8) degrees, beta
      = 112.417(10) degrees, gamma = 91.066(9) degrees, V = 1276.1(3) A(3), Z = 2. In
      77 K 3:1 EtOH/MeOH glassy solution, these colorless complexes exhibit weak red
      orange to red emissions originating from a lowest spin-forbidden ligand field
      excited state.

PMID- 11952387
TI  - KBa(2)InAs(3) with coexisting monomers of [In(2)As(7)](13-) and their one
      dimensional polymers.
AB  - The title compound was made by fusion of a stoichiometric mixture of the pure
      elements. The structure (orthorhombic, Cmc2(1), Z = 16, a = 10.129(2) A, b =
      25.208(4) A, c = 13.884(3) A) is made of isolated units of [In(2)As(7)](13-) and
      a polymer chain of [In(2)As(5)](7-) made of the same units. According to magnetic
      measurement, KBa(2)InAs(3) is a closed-shell compound, a Zintl phase.

PMID- 11952386
TI  - Biomimetic studies of terminal oxidases: trisimidazole picket metalloporphyrins.
AB  - Three biomimetic models for the binuclear Fe/Cu (heme/trisimidazole) active site
      of terminal oxidases, such as cytochrome c oxidase and related enzymes, have been
      prepared. Based upon a tetrakis(aminophenyl)porphyrin core, these models possess
      a single covalently linked imidazole-bearing tail on one side of the porphyrin
      and three imidazole "pickets" on the opposite side of the porphyrin ring. Three
      different imidazole picket motifs are characterized in free base, Fe, Zn, Fe/Cu,
      and Zn/Cu forms. A combination of NMR, EPR, and IR demonstrates that, for the N
      methylimidazole systems studied, the distal Cu is bound within the trisimidazole
      environment in the reduced (Cu(I)) and oxidized (Cu(II)) forms. The imidazole
      picket substitution pattern and state of metalation have significant influence on
      the interaction of these compounds with CO. For imidazole picket systems
      containing NH groups, intramolecular H bonds compete with Cu(I) coordination of
      the N donors.

PMID- 11952388
TI  - Unique 2:1 complex with a trans-chelating bis-pyridine ligand.

PMID- 11952389
TI  - The panacea.

PMID- 11952390
TI  - Optometry, technology, synergy and superiority.

PMID- 11952391
TI  - The present and potential impact of research on animal models for clinical
      treatment of stimulus deprivation amblyopia.
AB  - OBJECTIVE: With the benefit of hindsight based on an additional 20 years of
      research, we review a question posed originally by Marg of whether animal models
      for stimulus deprivation amblyopia in children are valid or useful for clinical
      application. METHOD: Following a review of relevant research on animal models,
      the human clinical literature on treatment of stimulus deprivation amblyopia has
      been reviewed with respect to past and current impact of animal research on
      clinical treatment. In addition, we speculate on the potential future clinical
      impact of animal work on developmental plasticity in the visual cortex that is
      directed towards an understanding of its underlying molecular basis. CONCLUSIONS:
      Animal research that has begun to define the timing, nature and sites of critical
      periods in the central visual pathways with greater precision than was known 20
      years ago has had a demonstrable impact on clinical practice. In turn, these
      changes in clinical practice have produced far better outcomes than prior to
      1980, for both the acuity of the amblyopic eye and for binocular functions such
      as stereopsis.

PMID- 11952392
TI  - Giant cell arteritis.
AB  - Giant cell arteritis has been considered an enigmatic disease. It is
      characterised by chronic granulomatous inflammation of the walls of large and
      medium-sized arteries. The process has a predilection for the extradural cranial
      arteries, which include the ophthalmic and the posterior ciliary arteries. It is
      a multi-symptom disease of older individuals and patients often present with
      challenging issues and diagnostic dilemmas. We review the literature and latest
      protocols for the diagnosis and management of giant cell arteritis.

PMID- 11952393
TI  - Retinal neurochemical changes following application of glutamate as a metablolic
      substrate.
AB  - BACKGROUND: Retinal neural and glial cells share an intricate relationship that
      includes uptake and recycling of the amino acid neurotransmitters, glutamate and
      gamma-amino butyric acid (GABA), as well as metabolic links. The aim of this work
      was to determine the neurochemical and morphological changes induced by the
      removal of glucose but with the provision of exogenous glutamate in the isolated
      retinal preparation incubated under aerobic conditions. The carbon skeleton of
      glutamate can enter the tricarboxylic acid cycle as alpha-ketogluterate,
      providing an alternative metabolic substrate in cases of glucose deprivation.
      METHODS: Isolated rat retinas were incubated in physiological media with and
      without glucose, using a range of glutamate concentrations to provide an
      alternative source of metabolic substrate. We conducted post-embedding
      immunocytochemistry and quantified the change in glutamate and GABA
      immunoreactivity within Muller cells under these different incubation conditions.
      RESULTS: The provision of glutamate with normal (6 mM) glucose levels resulted in
      a gradual accumulation of glutamate and GABA in Muller cells, with Muller loading
      when exogenous glutamate concentrations were above 0.1 mM. However, when these
      varying levels of glutamate were applied in the absence of glucose, glutamate
      accumulation in Muller cells was decreased compared to the 6 mM glucose condition
      and GABA accumulation in Muller cells was at a minimum at moderate (0.5 and 1 mM)
      glutamate levels. Under hypoglycaemic conditions, exogenous glutamate (0.5 to 1
      mM) is rapidly metabolised by Muller cells to the extent that no glial loading is
      evident, despite the high concentrations. CONCLUSIONS: Normal neurochemical
      function appears to be maintained secondary to exogenous glutamate provision of
      0.5 to 1 mM when glucose is not in the incubation medium, implying that glutamate
      can be used as an alternative metabolic substrate. We also show that Muller cells
      possess more rapid glutamate metabolic capabilities compared to the metabolism of
      GABA.

PMID- 11952394
TI  - Non-invasive tear break-up time in normal Malays.
AB  - BACKGROUND: Tear stability in normal Malays with consideration of gender and age
      has not been reported. In this study, we measured tear stability in normal Malays
      using the non-invasive tear break-up time (NIBUT). METHODS: Forty-eight Malay
      subjects aged seven to 60 years were recruited from among the staff, their
      children and students of the faculty. NIBUT was measured by noting the time taken
      for distortions to appear in a reflected image of a grid pattern formed on the
      corneal surface. RESULTS: The mean NIBUT of the sample was 15.8 +/- 9.4 (SD)
      seconds. The median was 14.6 seconds with range of 4.2 seconds to 48.6 seconds.
      The majority (73 per cent) of subjects had NIBUT values between six and 20
      seconds. There was no significant difference in NIBUT values between males and
      females but there was a decrease of NIBUT with age. CONCLUSION: The NIBUT values
      found in this study are comparable to those reported for Asian populations but
      much less than those of Western populations. Our findings point to the need for
      local clinical studies in contact lens and contact lens-related research as tear
      physiology of the local population may not be the same as in Western populations.

PMID- 11952395
TI  - Valsalva maculopathy.
AB  - The Valsalva manoeuvre comprises forcible exhalation against the closed glottis,
      thereby creating a sudden increase in the intrathoracic or intra-abdominal
      pressure. A simultaneous rapid rise in intraocular venous pressure may result in
      the spontaneous rupture of perifoveal capillaries, leading to a characteristic
      clinical picture of a preretinal haemorrhage in an otherwise healthy eye. The
      haemorrhage typically occurs at the macula and in the vast majority of cases
      resolves without compromising visual acuity. Valsalva maculopathy is an isolated
      and self-limited event. A case of Valsalva maculopathy in a young healthy male
      attributable to an incontrovertible Valsalva stress associated with weightlifting
      is presented.

PMID- 11952396
TI  - The case against protan drivers holding professional driving licenses.

PMID- 11952398
TI  - Duffy defends Optometry Council stance.

PMID- 11952397
TI  - New South Wales Board misrepresented.

PMID- 11952399
TI  - The site of amblyopia.

PMID- 11952400
TI  - Foundations of a solution to cataract blindness.

PMID- 11952401
TI  - What causes steroid cataracts? A review of steroid-induced posterior subcapsular
      cataracts.
AB  - Prolonged use of glucocorticoids is a significant risk factor for the development
      of posterior subcapsular cataract. This places restrictions on the use of
      glucocorticoids in the treatment of systemic and/or ocular inflammatory
      conditions as well as in organ transplantation. The mechanisms responsible for
      the opacification are unknown and no effective treatment, other than surgical
      removal of the lens, is available. Difficulties in establishing suitable in vivo
      or in vitro models have limited research in this area. Nevertheless, several
      mechanisms, based on observations with other types of cataracts, have been
      proposed. In this review, these mechanisms are evaluated in light of the evidence
      available. A novel mechanism is also proposed, in which steroids do not directly
      act on the lens but rather affect the balance of ocular cytokines and growth
      factors.

PMID- 11952402
TI  - Apoptosis is a feature of TGF beta-induced cataract.
AB  - BACKGROUND: Studies in our laboratory have shown that transforming growth factor
      beta (TGF beta) induces rodent lens epithelial cells to undergo aberrant growth
      and differentiation that reproduces morphological and molecular features of human
      anterior subcapsular cataract and posterior capsule opacification. In addition,
      features of apoptosis have been described in some forms of human cataract. In the
      present study we investigated apoptotic changes induced by TGF beta in our rodent
      models. METHODS: Lens epithelial explants and whole lenses from rats were
      cultured with TGF beta. Morphological analysis and TUNEL were used to detect
      apoptotic changes. Transgenic mice expressing a self-activating form of human TGF
      beta 1 in the lens were included in the analysis. RESULTS: TGF beta-induced cell
      loss in epithelial explants coincided with increased numbers of pyknotic nuclei.
      Some of these nuclei were TUNEL-positive. Studies on lenses cultured with TGF
      beta and lenses from transgenic mice showed that the subcapsular plaques that
      developed contained pyknotic nuclei and that many of these were TUNEL-positive.
      DISCUSSION: This study shows that cells develop morphological and molecular
      features of apoptosis in TGF beta-induced cataract models. This confirms that
      apoptosis can be included as another TGF beta-induced cellular change that mimics
      events in human cataract.

PMID- 11952403
TI  - Chaperone activity in the lens.
AB  - INTRODUCTION: alpha-crystallin, the major protein of the eye lens, is a molecular
      chaperone that is able to prevent the precipitation of denatured proteins. This
      activity is thought to be important for the maintenance of lens transparency.
      Loss of the activity has been postulated to contribute to the development of
      cataract. The purpose of this study was to determine how chaperone activity was
      affected by growth and ageing of the lens. METHODS: alpha-crystallins were
      purified from nine concentric tissue layers removed from an adult bovine lens.
      The ability to inhibit the precipitation of beta(L)-crystallin, following thermal
      denaturation, was used to assess the chaperone activity of these proteins. The
      molar ratio of alpha-crystallin/beta(L)-crystallin required to inhibit the
      precipitation of beta(L)-crystallin by 50 per cent was used as a measure of the
      affinity of the chaperone for denatured protein. RESULTS: As evidenced by a
      gradual increase in the ratio, from 0.52 to 1.24, the protective ability of alpha
      crystallin decreased from the outside of the lens into the centre. alpha
      crystallin from the cortex of the lens provided greater protection against
      precipitation of proteins than older alpha-crystallin from the nucleus. The
      reasons for this were investigated. Gel electrophoresis of the proteins from each
      concentric layer revealed an increase in degraded polypeptides from approximately
      one per cent in the cortex to more than nine per cent in the centre of the lens.
      This increase appears to be correlated with the decrease in chaperone ability.
      Renaturing alpha-crystallin obtained from the nucleus did not increase its
      chaperone activity, indicating conformational changes were not responsible for
      the decreased activity. Phosphorylation did not appear to have any significant
      effect on the chaperone activity. CONCLUSION: The loss of chaperone activity,
      accompanying fibre cell compression into the centre of the lens, can be
      attributed to degradation of the alpha-crystallin polypeptides.

PMID- 11952404
TI  - Cataract in the 21st Century: lessons from previous epidemiological research.
AB  - BACKGROUND: Cataract surgery is currently the most commonly performed ophthalmic
      procedure in Australia. The purpose of this paper is to review Australian data on
      cataract prevalence and risk factors and to project potential future demand for
      cataract services. METHODS: Age- and gender-specific cataract prevalence data
      from the Melbourne Visual Impairment Project (VIP) and the Blue Mountains Eye
      Study (BMES) were applied to population estimates from the Australian Bureau of
      Statistics. Published cataract risk factor data from the two studies were
      reviewed. RESULTS: Although the projected number of cataracts varies
      substantially based on the definition used, the relative number of cataracts will
      double over the next 50 years due to the aging of the population. Risk factors
      for cortical cataract identified in both the VIP and the BMES included female
      gender, sunlight exposure and myopia. Concordant findings for nuclear cataract
      included female gender, brown irides, cigarette smoking and myopia. The only risk
      factor for posterior subcapsular cataract (PSC) that was identified in both
      studies was myopia. Some of the discrepant findings between the two studies
      included alcohol intake, diabetes and medication use. DISCUSSION: These data
      suggest that supply and demand for cataract surgery must be considered and
      managed to maintain the current level of cataract surgery delivery as the number
      of people with cataract increases at a proportionately greater rate than the
      total population. The supply of cataract surgical services could be increased
      through an increase in the number of ophthalmologists, an increase in the
      efficiency with which cataract surgical services are delivered, or improved
      technology. The demand for cataract surgery could be decreased through the
      implementation of effective primary prevention strategies, although successful
      strategies are currently unknown and/or untested. Given our current state of
      knowledge about cataract, it seems most feasible immediately to alter the health
      service delivery side of the equation to reduce the public health burden of
      cataract.

PMID- 11952405
TI  - Is hypochlorous acid (HOCl) involved in age-related nuclear cataract?
AB  - BACKGROUND: Oxidative damage to lens proteins is associated with human age
      related nuclear cataract and H2O2 has been implicated. As hypochlorous acid
      (HOCl) can be formed from chloride ions and H2O2 and many of the protein
      modifications observed in cataract are also noted following exposure of proteins
      to HOCl, age-related nuclear cataract lenses were examined for evidence of HOCl
      mediated alterations. METHOD: Three techniques were employed using human lens
      samples: 1. staining with a HOP antibody that recognises HOCl-treated proteins,
      2. myeloperoxidase assays and 3. measurement of chlorotyrosine in acid digests of
      the crystallins. RESULTS: HOP staining was inconclusive, although cataract lenses
      appeared to stain more intensely than normals. No myeloperoxidase activity could
      be detected and neither mono- nor di-chlorotyrosine could be found in human lens
      proteins. CONCLUSIONS: On the basis of this study, no evidence was obtained to
      support a role for HOCl in age-related nuclear cataract.

PMID- 11952407
TI  - Robert Augusteyn. Director of the National Vision Research Institute of Australia
      1991 to 2001.

PMID- 11952406
TI  - Giant intracranial meningioma without hemianopic visual field loss.

PMID- 11952408
TI  - Vision and learning to read.

PMID- 11952409
TI  - Vision and learning to read.

PMID- 11952410
TI  - Vision and learning to read.

PMID- 11952411
TI  - Plasma membrane-bound mechanisms of signal transduction in the control of plant
      dormancy and resistance.
AB  - Data on membrane-bound biochemical mechanisms of control of plant dormancy and
      resistance to phytopathogens are discussed. Phytohormones are involved in the
      control of plant dormancy by the modification of activity of membrane-bound
      enzymes and ion channels. Similar constituents of the plasma membrane are
      influenced by fungal extracellular metabolites. Proposed interconnections between
      plasmalemma-bound signaling mechanisms responsible for plant resistance to
      infection and dormancy regulation are illustrated by a scheme.

PMID- 11952412
TI  - Reactive oxygen species as essential components of ambient air.
AB  - In this review evidence for the presence of the anion radical O2(-*) in
      atmospheric air is considered, and the biological activity of superoxide and
      negative air ions is compared. Various aspects of the biological effect of
      superoxide and other reactive oxygen species contained in air at the cell,
      tissue, and organism levels are discussed. The results of the therapeutic use of
      exogenous gaseous superoxide and low doses of H2O2 for the treatment of bronchial
      asthma, pain, and Parkinson's disease are reported. A hypothesis on the mechanism
      of physiological action of exogenous reactive oxygen species is discussed.

PMID- 11952413
TI  - Quality control: proteins and organelles.
AB  - This review summarizes materials on the mechanisms of intracellular degradation
      of proteins whose topogenesis is disturbed at one stage or another. Chaperone and
      proteolytic systems involved in this process in the endoplasmic reticulum,
      mitochondria, and chloroplasts of eucaryotic cells as well as those in distinct
      subcellular compartments of procaryotic cells are considered. The available data
      suggest that living cells contain numerous systems keeping under control both
      folding of newly synthesized and newly imported polypeptide chains and their
      incorporation into heterooligomeric complexes. The point of view is elaborated
      that organelle formation is controlled not only at the level of individual
      protein molecules but also at the supermolecular level when whole organelles
      incapable of carrying out their integral key functions become targets for partial
      or total elimination. This type of control is realized through an autophagic
      mechanism involving lysosomes/vacuoles.

PMID- 11952414
TI  - Phosphonates and their degradation by microorganisms.
AB  - Phosphonates are a class of organophosphorus compounds characterized by a
      chemically stable carbon-to-phosphorus (C-P) bond. Wide occurrence of
      phosphonates among xenobiotics polluting the environment has aroused interest in
      pathways and mechanisms of their biodegradation. Only procaryotic microorganisms
      and the lower eucaryotes are capable of phosphonate biodegradation via several
      pathways. Destruction of the non-activated C-P bond by the C-P lyase pathway is
      of fundamental importance, and understanding of the process is a basic problem of
      biochemistry and physiology of microorganisms. This review offers analysis of
      available data on phosphonate-degrading microorganisms, degradation pathways, and
      genetic and physiological regulation of this process.

PMID- 11952415
TI  - Tungsten-containing enzymes.
AB  - The biological importance of tungsten has been fully proved in the last decade
      due to isolation of a number of tungsten-containing enzymes (W-enzymes) from
      hyperthermophilic archaea. Tungsten was previously considered only as an
      antagonist of molybdenum, because the replacement of molybdenum by tungsten (due
      to their chemical similarity) leads to inactivation of molybdenum-containing
      enzymes (Mo-enzymes). In addition to the "true W-enzymes" in which tungsten
      cannot be replaced by molybdenum, recently some enzymes have been isolated which
      can use either molybdenum or tungsten in the catalytic process. This review
      briefly summarizes data on the participation of tungsten in catalysis by some
      enzymes and the structure of the active sites of W-enzymes.

PMID- 11952416
TI  - New structures of the O-specific polysaccharides of Proteus. 2. Polysaccharides
      containing O-acetyl groups.
AB  - Structures of five new O-specific polysaccharides of Proteus bacteria were
      established. Four of them, Proteus penneri 4 (O72), Proteus vulgaris 63/57 (O37),
      Proteus mirabilis TG 277 (O69), and Proteus penneri 20 (O17), contain O-acetyl
      groups in non-stoichiometric quantities, and the polysaccharide of P. penneri 1
      is structurally related to that of P. penneri 4. The structures were elucidated
      using NMR spectroscopy, including one-dimensional 1H- and 13C-NMR spectroscopy,
      two-dimensional 1H,1H correlation (COSY, TOCSY), H-detected 1H,13C heteronuclear
      multiple-quantum coherence (HMQC), heteronuclear multiple-bond correlation
      (HMBC), and nuclear Overhauser effect spectroscopy (NOESY or ROESY), along with
      chemical methods. The structural data obtained are useful as the chemical basis
      for the creation of the classification scheme for Proteus strains.

PMID- 11952417
TI  - Apoptosis in the initial leaf of etiolated wheat seedlings: influence of the
      antioxidant ionol (BHT) and peroxides.
AB  - Apoptosis was observed in the initial leaf of 5-8-day-old etiolated wheat
      seedlings. A condensation of cytoplasm in apoptotic cells, formation of myelin
      like structures, specific fragmentation of cytoplasm, appearance in vacuoles of
      specific vesicles containing subcellular organelles, condensation and margination
      of chromatin in the nucleus, and internucleosomal fragmentation of nuclear DNA
      are ultrastructural features of apoptosis in the initial wheat leaf. Single
      membrane vesicles detected in vacuoles of the leaf cells resemble in appearance
      the vacuolar vesicles in the coleoptile apoptotic cells described earlier
      (Bakeeva, L. E., et al. (1999) FEBS Lett., 457, 122-125); they contain
      preferentially plastids but not mitochondria as was observed in coleoptile. The
      vacuolar vesicles are specific for the apoptotic plant cells. Thus, apoptosis in
      various tissues is an obligatory element of plant (wheat) growth and development
      even in the early stages of ontogenesis. Contrary to strong geroprotecting action
      in coleoptile, the known antioxidant BHT (ionol, 2.27 x 10(-4) M) does not
      prevent in the leaf cells the apoptotic internucleosomal DNA fragmentation and
      appearance of specific vacuolar vesicles containing subcellular organelles.
      Therefore, the antioxidant action on apoptosis in plants is tissue specific.
      Peroxides (H2O2, cumene hydroperoxide) stimulated apoptosis (internucleosomal DNA
      fragmentation) in coleoptile and induced it in an initial leaf when apoptosis in
      a control seedling leaf was not yet detected. Thus, apoptosis that is programmed
      in plant ontogenesis and controlled by reactive oxygen species (ROS) can be
      modulated by anti- and prooxidants.

PMID- 11952418
TI  - Respiration and mitochondrial membrane potential are not required for apoptosis
      and anti-apoptotic action of Bcl-2 in HeLa cells.
AB  - The release of cytochrome c from intermembrane space of mitochondria into cytosol
      is one of the critical events in apoptotic cell death. The important anti
      apoptotic oncoprotein Bcl-2 inhibits this process. In the present study it was
      shown that apoptosis and release of cytochrome c induced by staurosporine or by
      tumor necrosis factor-alpha in HeLa cells were not affected by inhibitors of
      respiration (rotenone, myxothiazol, antimycin A) or by uncouplers (CCCP, DNP)
      that decrease the membrane potential at the inner mitochondrial membrane. The
      inhibitors of respiration and the uncouplers did not affect also the anti
      apoptotic activity of Bcl-2.

PMID- 11952419
TI  - Biologically active oligosaccharides from pectins of Pisum sativum L. seedlings
      affecting root generation.
AB  - Two physiologically active oligosaccharide fractions were isolated from pectin of
      Pisum sativum L. cell wall after its partial acid hydrolysis. These fractions
      displayed stimulating and inhibiting effects on root formation in thin-layer
      explants. The subsequent separation of these fractions by gel permeation and
      anion-exchange chromatography resulted in fractions with effective concentrations
      two orders of magnitude lower than the concentrations of the initial fractions.
      The resulting oligosaccharides displayed their effect on the earliest stage of
      the rhizogenesis associated with formation of root primordias. The rhizogenesis
      inhibiting fraction suppressed cell division by 30-50%. The stimulating fraction
      mainly contained fragments of xyloglucan and galactan, and the inhibiting
      fraction contained fragments of xyloglucan, galactan, and arabinan. The
      polymerization degrees of the stimulating and of the inhibiting oligosaccharides
      were 10-11 and 5-6, respectively.

PMID- 11952420
TI  - Effect of activators and blockers of ligand-regulated ion channels on the
      activity of the Cl-stimulated Mg2+-ATPase of the plasma membrane fraction from
      bream (Abramis brama L.) brain.
AB  - Effects of GABA, glycine, acetylcholine, and glutamate (agonists of the
      GABAa/benzodiazepine, glycine, choline, and glutamate receptors, respectively) at
      concentrations in the range 10(-8)-10(-4) M on the activity of "basal" Mg(2+)
      ATPase of the plasma membrane fraction from bream brain and on its activation by
      Cl(-) were investigated. GABA and glycine activated "basal" Mg(2+)-ATPase
      activity and suppressed its activation by Cl(-). Acetylcholine and glutamate
      activated "basal" Mg(2+)-ATPase to a lesser extent and did not suppress the
      activation of the enzyme by Cl(-). The activation of "basal" Mg(2+)-ATPase by
      neuromediators was decreased by blockers of the corresponding receptors
      (picrotoxin, strychnine, benztropine mesylate, and D-2-amino-5-phosphonovaleric
      acid). In addition, picrotoxin and strychnine eliminated the inhibiting effect of
      GABA and glycine, respectively, on the Cl(-)-stimulated Mg(2+)-ATPase activity.
      Agonists of the GABAa/benzodiazepine receptor--phenazepam (10(-8)-10(-4) M) and
      pentobarbital (10(-6)-10(-3) M)--activated the "basal" Mg(2+)-ATPase activity and
      decreased the Cl(-)-stimulated Mg(2+)-ATPase activity. The dependence of both
      enzyme activities on ligand concentration is bell-shaped. Moreover, phenazepam
      and pentobarbital increased the "basal" Mg(2+)-ATPase activity in the presence of
      10(-7) M GABA and did not influence it in the presence of 10(-4) M GABA and 10(
      6) M glycine. The data suggest that in the fish brain membranes the Cl(-)
      stimulated Mg(2+)-ATPase interacts with GABAa/benzodiazepine and glycine
      receptors but not with m-choline and glutamate receptors.

PMID- 11952421
TI  - Changes in the balance between membrane-bound and soluble forms of CD95 (Fas)
      during selection of tumor cells in vivo.
AB  - Studies concerning the expression of the receptor CD95 (Fas) by tumor cells and
      the role of this protein in apoptosis induced by the effector host cells that
      bear Fas-ligand are mainly focused on the membrane-bound form of Fas. There are
      only a few data about the production of the soluble form of Fas by the tumor
      cells, its role in the interaction with the effector host cells, and the possible
      changes in the synthesis of this protein during tumor progression. In the present
      work, three in vitro transformed parental cell lines of different origin and 24
      of their variants isolated after a short cycle of natural selection in vivo were
      studied. It was demonstrated for the first time that: 1) production of the
      soluble Fas by all selected in vivo variant tumor cell lines increased
      significantly (2-10-fold) in comparison to the initial (parental) cell lines and
      did not depend on the origin of the parental lines. At the same time, the
      expression of the membrane-bound form of Fas decreased considerably; 2)
      variations of the balance between membrane-bound and soluble forms of Fas in
      selected in vivo variant cells and the expression of the [H(2)O(2)(CA) + PGE(S)]
      phenotype by these cells (this phenotype determines one of the essential
      mechanisms of the protection of a tumor cell in vivo) possibly represent
      independent secondary changes acquired during tumor progression in vivo.

PMID- 11952422
TI  - Induction of apoptosis in rat myocardium under anoxic conditions.
AB  - The effect of anoxic incubation of small slices of isolated rat hearts on
      respiration, internucleosomal DNA fragmentation, and mitochondrial ultrastructure
      was investigated. Anoxic incubation for 72 h induced apoptosis accompanied by
      internucleosomal DNA fragmentation and changes in respiration and mitochondrial
      ultrastructure. The mitochondrial population was characterized by morphological
      heterogeneity. In a significant part of the mitochondrial population there were
      signs of mitochondrial swelling and appearance of electron-dense mitochondria.
      Anoxia also induced the appearance of an atypical (and previously unknown)
      population of small electron-dense mitochondria. They were characterized by
      unusual localization inside electron-light mitochondria. Under anoxic conditions
      the inner mitochondrial membrane formed electron-dense ordered structures. All
      changes described here reflect two opposing processes occurring in mitochondria:
      apoptotic destruction and compensatory processes responsible for maintenance of
      mitochondria.

PMID- 11952423
TI  - Suppression of programmed cell death by intracellular cAMP is not mediated by
      expression of genes encoding an inhibitor of apoptosis.
AB  - The elevation of intracellular cAMP content is accompanied by expression of genes
      whose promoter contains a Ca(2+)-cAMP responsive element. In vascular smooth
      muscle cells (VSMC), activation of cAMP signaling blocks apoptosis triggered by
      serum deprivation. In the present study we investigated the role of gene
      expression in the inhibition of apoptosis by cAMP. In VSMC transfected with E1A
      adenovirus, incubation in the absence of serum for 6 h led to 20-fold elevation
      of chromatin fragmentation and 10-fold activation of caspase-3 activity, these
      being employed as markers of apoptosis. Forskolin-induced activation of cAMP
      signaling was accompanied by 50% elevation of RNA synthesis and completely
      abolished the development of apoptosis during the initial 6 h incubation in
      growth factor-free medium. In 12 h apoptosis in forskolin-treated VSMC was slowly
      developed and after 24 h the content of chromatin fragments was 2-fold less than
      in control cells. Addition of actinomycin D and cycloheximide completely blocked
      RNA synthesis and decreased protein synthesis by 80%, respectively. Neither
      compound affected baseline apoptosis or its inhibition by forskolin. More than 70
      newly phosphorylated proteins were observed by 2D-electrophoresis of VSMC after
      incubation with forskolin for 3 h; in 24 h the number of phosphoproteins
      triggered by forskolin was decreased by 2-3-fold. These results show that
      suppression of VSMC apoptosis under activation of cAMP signaling is mediated via
      posttranslational modification of pre-existing intermediates of the apoptotic
      machinery rather than by de novo synthesis of inhibitors of programmed cell
      death.

PMID- 11952424
TI  - Isolation and characterization of tightly coupled mitochondria from wild type and
      nap mutant Neurospora crassa.
AB  - A fast and reproducible procedure was elaborated for isolation of tightly coupled
      mitochondria from wild type and nap-mutant Neurospora crassa cells harvested at
      different growth stages. The isolated mitochondrial preparations had controlled
      metabolic states and were tightly coupled, i.e., displayed good respiratory
      control and had close to the theoretically expected maximal ADP/O ratios upon
      oxidation of Krebs cycle intermediates and exogenous NADH. They contained the
      fully competent respiratory chain with all three points of energy conservation.
      Oxidation of all examined substrates by mitochondria from both wild type and
      mutant cells was mediated by two alternative terminal oxidative systems, albeit
      to varying extent, with the more pronounced engagement of the alternative oxidase
      in the stationary growth phase and with a minor contribution of this non
      phosphorylating pathway in the substrate oxidation by mutant mitochondria.
      Oxidation of NAD-dependent substrates by mitochondria from the two cell types was
      accommodated via both rotenone-sensitive and rotenone-insensitive pathways, while
      the level of rotenone-insensitive pathway in mutant cells was lower than in wild
      type cells. It is suggested that a more limited contribution of alternative non
      phosphorylating oxidative pathways to the total respiration in mutant cells, as
      compared with wild type cells, could, at least partially, explain an elevated ATP
      level in these cells. However, the absence of principal differences in the
      arrangement of the respiratory chain in mitochondria of wild type and mutant
      cells implies that the elevated ATP level in the nap mutant is largely related to
      reduced ATP expenses for transport processes in these cells.

PMID- 11952425
TI  - New structures of the O-specific polysaccharides of bacteria of the genus
      Proteus. 1. Phosphate-containing polysaccharides.
AB  - The O-specific polysaccharide chains (O-antigens) of the lipopolysaccharides of
      five Proteus strains, P. vulgaris O17, P. mirabilis O16 and O33, and P. penneri
      31and 103, were found to contain phosphate groups that link the non sugar
      components, e.g., ethanolamine and ribitol. The polysaccharides of P. mirabilis
      O16 and P. penneri 103 include ribitol phosphate in the main chain and thus
      resemble ribitol teichoic acids of Gram-positive bacteria. The structures of the
      polysaccharides were elucidated using NMR spectroscopy, including two-dimensional
      1H,1H correlation spectroscopy (COSY and TOCSY), nuclear Overhauser effect
      spectroscopy (NOESY or ROESY), and H-detected 1H,13C and 1H,31P heteronuclear
      multiple-quantum coherence spectroscopy (HMQC), along with chemical methods. The
      structures determined are unique among the bacterial polysaccharides and,
      together with the data obtained earlier, represent the chemical basic for
      classification of Proteus strains. Based on structural similarities of the O
      specific polysaccharides and serological relationships between the O-antigens, we
      propose to extend Proteus serogroups O17 and O19 by including P. penneri strains
      16 and 31,respectively.

PMID- 11952426
TI  - Study of the kinetics of oxidation of monophenols by tyrosinase. The effect of
      reducers.
AB  - Kinetics of oxidation of monophenols by tyrosinase from the fungus Aspergillus
      flavipes 56003 and the effect of Fe2+, serine, and ascorbic acid on this reaction
      were studied. The effectors were shown to accelerate the oxidation of
      monophenols, decreasing the lag-time of the reaction. It is assumed that the
      activation of the tyrosinase in the presence of Fe2+ is due to a direct reduction
      of the active site copper ions. Serine and ascorbic acid are supposed to affect
      the reaction of quinone transformation. The activation of the enzyme in the
      presence of Fe2+ suggests that the oxidation of monophenols is an autocatalytic
      process.

PMID- 11952427
TI  - Assembly of the ribonucleoprotein complex containing the mRNA of the beta-subunit
      of the mitochondrial H+-ATP synthase requires the participation of two distal cis
      acting elements and a complex set of cellular trans-acting proteins.
AB  - The mRNA encoding the beta-subunit of the mitochondrial H(+)-ATP synthase (beta
      F1-ATPase) is localized in an approx. 150 nm structure of the hepatocyte of
      mammals. In the present study, we have investigated the cis- and trans-acting
      factors involved in the generation of the ribonucleoprotein complex containing
      beta-F1-ATPase mRNA. Two cis-acting elements (beta1.2 and 3'beta) have been
      identified. The beta1.2 element is placed in the open reading frame, downstream
      of the region encoding the mitochondrial pre-sequence of the protein. The 3'beta
      element is the 3' non-translated region of the mRNA. Complex sets of proteins
      from the soluble and non-soluble fractions of the liver interact with the beta1.2
      and 3'beta elements. A soluble p88, present also in reticulocyte lysate, displays
      binding specificity for both the cis-acting elements. Sedimentation and high
      resolution in situ hybridization experiments showed that the structure containing
      the rat liver beta-F1-ATPase mRNA is found in fractions of high sucrose
      concentration, where large polysomes sediment. Treatment of liver extracts with
      EDTA promoted the mobilization of beta-F1-ATPase mRNA to fractions of lower
      sucrose concentration, suggesting that the structure containing beta-F1-ATPase
      mRNA is a large polysome. Finally, in vitro reconstitution experiments with
      reticulocyte lysate, using either the full-length, mutant or chimaeric versions
      of beta-F1-ATPase mRNA, reveal that the assembly of the beta-F1-ATPase mRNA
      polysome requires the co-operation of both the cis-acting mRNA determinants. The
      present study illustrates the existence of an intramolecular RNA cross-talking
      required for the association of the mRNA with the translational machinery.

PMID- 11952429
TI  - Relax, be aware, and know what you are doing.

PMID- 11952428
TI  - An open reading frame in intron seven of the sea urchin DNA-methyltransferase
      gene codes for a functional AP1 endonuclease.
AB  - Analysis of the genome structure of the Paracentrotus lividus (sea urchin) DNA
      methyltransferase (DNA MTase) gene showed the presence of an open reading frame,
      named METEX, in intron 7 of the gene. METEX expression is developmentally
      regulated, showing no correlation with DNA MTase expression. In fact, DNA MTase
      transcripts are present at high concentrations in the early developmental stages,
      while METEX is expressed at late stages of development. Two METEX cDNA clones
      (Met1 and Met2) that are different in the 3' end have been isolated in a cDNA
      library screening. The putative translated protein from Met2 cDNA clone showed
      similarity with Escherichia coli endonuclease III on the basis of sequence and
      predictive three-dimensional structure. The protein, overexpressed in E. coli and
      purified, had functional properties similar to the endonuclease specific for
      apurinic/apyrimidinic (AP) sites on the basis of the lyase activity. Therefore
      the open reading frame, present in intron 7 of the P. lividus DNA MTase gene,
      codes for a functional AP endonuclease designated SuAP1.

PMID- 11952430
TI  - Intraoperative awareness: detected by the structured Brice interview?
AB  - BACKGROUND: Awareness is a rare complication in general anesthesia, but its
      consequences are stressful. Efforts must be undertaken to prevent, diagnose, and,
      if occurring, treat it. The incidence of awareness is higher following anesthesia
      involving the use of muscle relaxants. As a part of a quality assurance program
      at our short-stay surgery all patients exposed to general anesthesia are
      routinely subjected to a Brice interview, which aims to evaluate our standard
      anesthetic technique regarding awareness. METHODS: The Brice interview was used
      prospectively in 5216 patients given a propofol/opioid anesthetic for day-case or
      short-stay surgery. Neuromuscular blocks were used only for surgical needs, not
      routinely. All patients were interviewed on discharge from the recovery room. A
      second interview, according to Brice, was undertaken by telephone 3-7 days later
      in the case of a notable intraoperative event, or otherwise after postoperative
      patient complaints. All patients were also interviewed by telephone 1-2 days
      postoperatively. RESULTS: None of the patient interviews indicated awareness.
      This was also the case in five non-relaxed patients who had an incident of light
      anesthesia with eye opening and gross motor response without forewarning.
      Neuromuscular blockade was used in 7% of patients. DISCUSSION: We were unable to
      detect intraoperative awareness. The anesthetic regimen, including minimal use of
      muscle relaxants, might be beneficial for awareness prevention. Alternatively,
      the diagnostic power, the timing of the Brice interview, or the number of
      interviews performed may be questioned.

PMID- 11952431
TI  - Evaluation of remifentanil as single drug for awake fiberoptic intubation.
AB  - BACKGROUND: Awake fiberoptic intubation is the standard of care for difficult
      airway management. Quality and success of this technique depend on the experience
      of the intubating physician and the proper preparation of the patient. The aim of
      this study was to compare remifentanil (R) as single agent to the combination of
      fentanyl (F) and midazolam (M), which have been the drugs for analgesia and
      sedation for this procedure. METHODS: Seventy-four adult patients requiring
      nasotracheal intubation were randomly assigned to one of two groups. In group I,
      (n=37) R was administered in incremental dosages (0.1-0.25-0.5 microg/kg/min) by
      an infusion pump according to comfort, level of sedation and respiratory
      depression. In group II, (n=37) analgesia and sedation was achieved by F 1.5
      microg/kg and doses of between 1 and 10 mg M, titrated to the individual needs.
      Patient reactions like grimacing, movement and coughing during intubation were
      assessed, as well as patient recall of the procedure. Haemodynamic and
      respiratory parameters were continuously recorded. RESULTS: Group I patients
      better tolerated nasal tube passage (P<0.001) and laryngeal tube advancement
      (P<0.001) than group II. Remifentanil better suppressed hemodynamic response to
      nasal intubation (P<0.001). No significant difference in respiratory data was
      recorded. In group I more recall of the procedure was observed (six vs. zero
      patients, P<0.05). CONCLUSION: Remifentanil in high doses, as the single agent
      for patient preparation for awake fiberoptic intubation seems to improve
      intubating conditions, quality and reliability of the procedure. However, a
      higher incidence of recall is to be expected.

PMID- 11952432
TI  - Remifentanil infusion for cardiac catheterization in children with congenital
      heart disease.
AB  - BACKGROUND: Cardiac catheterization of children with congenital heart disease is
      increasingly being performed under general anesthesia. Haemodynamic stability
      during anesthesia and fast and adequate recovery after the procedure is crucial
      in these patients. We performed a pilot study to evaluate hemodynamic stability
      when using remifentanil for anesthesia during cardiac catheterization. We also
      evaluated extubation times and recovery characteristics. METHODS: In a
      randomized, prospective, double-blind study 30 children (aged 1.5-20 months)
      received a continuous infusion of either 0.2 (group 0.2) or 0.3 microg/kg/min
      remifentanil (group 0.3) as part of a balanced anesthesia with 0.6 MAC
      sevoflurane. Heart rate, noninvasive arterial blood pressure, end tidal CO2 and
      pulse oxymetry were monitored throughout the procedure. Extubation times were
      noted, and recovery from anesthesia was evaluated using Aldrete scores. RESULTS:
      : Haemodynamic response to intubation was well blunted in both groups. No
      significant changes in hemodynamic variables were noted from induction of
      anesthesia until 10 min after intubation. From then on there was a decrease in HR
      and systolic arterial pressure, which remained significant throughout the
      procedure in both groups. Extubation times were similar in both groups: 7.3 min
      (2,1) in group 0.2 vs. 6.6 min (2,1) in group 0.3 (NS). The number of patients
      with an Aldrete score of nine or more was 14 (group 0.2) vs. 15 (group 0.3), 10
      min after extubation (NS). CONCLUSION: Both dose regimens of remifentanil
      provided stable hemodynamic conditions during anesthesia for cardiac
      catheterization of children with congenital heart disease and allowed for rapid
      and adequate recovery.

PMID- 11952433
TI  - Propofol infusion rate does not affect local pain on injection.
AB  - BACKGROUND: Local pain at the site of an i.v. injection of propofol is a well
      known problem, particularly in infants. This randomised investigator-blinded
      crossover study was designed to assess the effect of the i.v. bolus infusion rate
      on propofol-induced pain at the site of injection. METHODS: Thirty unpremedicated
      patients scheduled for ear-nose-throat or plastic surgery at Malmo University
      Hospital, Sweden, were given two consecutive 2.0 ml injections of propofol 10
      mg/ml (Diprivan, AstraZeneca, Sweden/UK), at different infusion rates (0.2 or 1.0
      ml/s), immediately before induction of general anesthesia. Half of the patients
      (n=15) received the first bolus of propofol over 2 s and the second bolus over 10
      s, and the other half (n=15) had their injections in reversed order. After each
      injection, the patient was asked by an investigator to indicate pain intensity on
      a visual analog scale (VAS) and to report the times of the appearance, maximum
      point and disappearance of pain. The injections were given approximately 2 min
      apart. The investigators scoring pain intensity, as indicated by the patients on
      a 10-point numerical rate scale, were blinded to the order in which the
      injections were given, as were the patients themselves. RESULTS: There were no
      statistically significant differences in the incidence (both 86%) of intensity
      (median; 25th; 75th percentiles, in VAS units: 3.1; 1.0; 5.3 and 3.3; 1.4; 5.0,
      respectively) or duration (66+/-31 and 73+/-26 s, respectively) of pain between
      the faster (1.0 ml/s) and slower (0.2 ml/s) bolus infusion rates of propofol
      studied. CONCLUSIONS: We conclude that the i.v. bolus infusion rate of propofol
      does not influence drug-induced local pain on injection, at least not within the
      infusion rate interval studied. Therefore, adjusting i.v. injection speed does
      not seem to be a clinically useful tool for reducing the intensity or duration of
      propofol-induced pain at the site of administration.

PMID- 11952434
TI  - Double-blind comparison of the variability in spontaneous recovery of
      cisatracurium- and vecuronium-induced neuromuscular block in adult and elderly
      patients.
AB  - BACKGROUND: This study was designed to compare variability in the offset of two
      neuromuscular blocking agents with different elimination pathways. METHODS: The
      spontaneous recovery profiles of cisatracurium and vecuronium were compared in
      adult (18-64 years) and elderly (> or =65 years) patients receiving
      N2O/O2/fentanyl/propofol anaesthesia. Patients were randomised to receive an
      initial bolus dose and maintenance doses of 3xED95, respectively, 0.6xED95 for
      cisatracurium (0.15 and 0.03 mg.kg-1) or 2xED95, respectively, and 0.4xED95 for
      vecuronium (0.1 and 0.02 mg.kg(-1)), as recommended in their prescribing
      information. Administration of the study drugs was double-blinded, and
      neuromuscular transmission was monitored using mechanomyography of the evoked
      response of the adductor pollicis, following ulnar nerve stimulation. RESULTS:
      The clinically effective duration (minutes) of the initial bolus dose, defined as
      the mean time to 25% T1 recovery (+/-SD), for the adult and elderly patients was
      53.5+/-9.8 and 57.3+/-11.5 for cisatracurium, respectively, and 34.1+/-9.0 and
      47.5+/-14.4 for vecuronium, respectively. The duration of spontaneous sufficient
      recovery (SSR), defined as the mean (+/-SD) time interval in minutes from 25% T1
      recovery to a T4:T1 ratio > or =0.8 after the last bolus dose, for the adult,
      respectively, elderly patients was 28.3+/-8.0 and 31.7+/-10.0 for cisatracurium
      and 38.5+/-13.2 and 60.3+/-26.1 for vecuronium. CONCLUSION: Whereas both the
      clinically effective duration and the duration of SSR are comparable between the
      adult and the elderly patients receiving cisatracurium, they differ substantially
      between these two age groups for vecuronium. Furthermore, the variability in
      offset is significantly lower in patients receiving cisatracurium, especially in
      the elderly, which may be of particular clinical interest.

PMID- 11952435
TI  - Oral clonidine premedication reduces the EC50 of propofol concentration for
      laryngeal mask airway insertion in male patients.
AB  - BACKGROUND: Oral clonidine, an alpha2-adrenergic receptor agonist, reduces the
      dose of propofol required for laryngeal mask airway (LMA) insertion. Target
      controlled infusion (TCI) is becoming increasingly popular for propofol infusion.
      There is no information, however, on the propofol blood concentrations required
      for LMA insertion and the effect of oral clonidine premedication on these values.
      METHODS: Propofol at target effect-site concentrations from 4.0 to 12.0 microg/ml
      were randomly administered using TCI in three groups of healthy male patients
      (n=35 each) who were undergoing elective orthopedic surgery: control, 2.5
      microg/kg clonidine, and 5.0 microg/kg clonidine groups. Nothing was administered
      to the control group. Clonidine(2.5 microg/kg or 5.0 microg/kg) was administered
      orally 90 min before arrival at the operating room in the clonidine groups. After
      equilibration between the blood- and effect-site for 15 min, insertion of the LMA
      was attempted. The EC50 for LMA insertion (measured propofol serum concentration
      in equilibrium with the effect-site at which 50% of patients do not respond to
      the insertion of the LMA) was determined by logistical regression. RESULTS:
      EC50+/-standard error values in the control, 2.5 microg/kg clonidine, and 5.0
      microg/kg clonidine groups were 8.72+/-0.55, 7.76+/-0.60, and 5.84+/-0.58
      microg/ml, respectively. The EC50 in the 5.0 microg/kg clonidine group was
      significantly lower than that in the control group (P < 0.01). CONCLUSIONS: The
      propofol concentration required for LMA insertion in healthy male patients is
      reduced by premedication with 5.0 microg/kg oral clonidine.

PMID- 11952436
TI  - Increased synthesis of nitric oxide in rat brain cortex due to halogenated
      volatile anesthetics confirmed by EPR spectroscopy.
AB  - BACKGROUND: Halogenated volatile anesthetics (HVAs) are considered to be
      inhibitors of nitric oxide synthase (NOS). On other hand, NO mediates the
      vasodilation produced by HVAs. Thus, both increase and decrease of NO
      concentration in brain tissues are possible during anesthesia. Previously, we
      have observed an increase of NO content in rat brain cortex under halothane
      anesthesia. The goal of this study was to determine whether the observed
      phenomenon was general for this anesthetic group, if it was specific for brain
      cortex, and if the NO increase was due changes in NOS activity. METHODS: NO
      scavengers were injected to adult rats 30 min prior to anesthesia. Rats were
      anesthetized by inhalation of an O2 mixture with volatile anesthetics (1.5% for
      halothane; 1% for isoflurane, 2% for sevoflurane). After 30 min of anesthesia,
      rats were decapitated and brain cortex, cerebellum, liver, heart, kidneys and
      testes were dissected, frozen in liquid nitrogen and subjected to EPR
      spectroscopy. Nitric oxide content was determined quantitatively based on the
      intensity of the NO-Fe-DETC complex spectrum and its comparison with the
      calibration curve. RESULTS: In rats anesthetized with HVAs, we observed a greater
      than twofold increase of NO content in brain cortex as compared to the
      nonanesthetized animals. No significant changes were detected in other organs.
      The NOS inhibitor N(omega)-nitro-L-arginine abolished the increase of NO content
      in brain produced by volatile anesthetics. CONCLUSION: The action of volatile
      anesthetics is coupled with an increase of NO content in the cortex dependent on
      NOS activity.

PMID- 11952437
TI  - Serum concentration of S-100 protein in assessment of cognitive dysfunction after
      general anesthesia in different types of surgery.
AB  - BACKGROUND: S-100 protein serum concentration (S-100) serves as a marker of
      cerebral ischemia in cardiac surgery, head injury and stroke. In these
      circumstances S-100 corresponds well with the results of neuropsychological
      tests. The aim of the present study was to investigate the value of S-100 and
      neuron specific enolase (NSE) in reflecting postoperative cognitive deficit
      (POCD) after general surgical procedures. METHODS: One hundred and twenty
      patients undergoing vascular, trauma, urological or abdominal surgery were
      investigated. Serum values of S-100 and NSE were determined preoperatively and
      0.5, 4, 18 and 36 h postoperatively. Neuropsychological tests for detecting POCD
      were performed preoperatively and on day 1, 3, and 6 after the operation. A
      decline of more than 10% in neuropsychological test results was regarded as POCD.
      Furthermore, we retrospectively compared the S-100 in patients with and without
      POCD in different types of surgery. RESULTS: According to our definition, forty
      eight patients had POCD (95% confidence interval: 37.5-58.5). These patients
      showed higher serum concentrations of S-100 (median 024 ng/ml; range 0.01-3.3
      ng/ml) compared with those without POCD (n=69; median 0.14 ng/ml; range 0-1.34
      ng/ml) 30 min postoperatively (P=0.01). Neuron specific enolase was unchanged
      during the course of the study. Differences of S-100 in patients with and without
      POCD were found in abdominal and vascular surgery but not in urological surgery.
      CONCLUSION: When all patients are pooled, S-100 appears to be suitable in the
      assessment of incidence, course and outcome of cognitive deficits. We suspect
      that in some surgical procedures, such as urological surgery, S-100 appears to be
      of limited value in detecting POCD. Neuron specific enolase did not reflect
      neuropsychological dysfunction after noncardiac surgery.

PMID- 11952438
TI  - Ultrasound-guided central venous cannulation in infants and children.
AB  - BACKGROUND: Percutaneous central venous cannulation in infants and children is a
      challenging procedure. Traditionally, an external landmark technique has been
      used to identify puncture site. An ultrasound-guided technique is now available
      and we wanted to evaluate this method in children and infants, looking
      specifically at the ease of use, success rate and complications. METHODS: Forty
      two consecutive infants and children (median 16.5 [0-177] months and 10 [3-45]
      kg) scheduled for central venous catheter placement were registered. An
      ultrasound scanner made for guiding puncture of vessels was used. After locating
      the puncture site, a sterile procedure was performed using an accompanying kit to
      aid puncture of the vessel. RESULTS: Cannulation was successful in all patients
      and we had no complications during insertion of the catheters. The right internal
      jugular vein was preferred in most patients, and in 95% of the patients the vein
      was punctured at the first attempt. The median time from start of puncture to
      aspiration of blood was 12 (3-180) seconds. CONCLUSION: The ultrasound-guided
      technique for placement of central venous catheters was easy to apply in infants
      and children. It is our impression that it increased the precision and safety of
      the procedure in this group of patients.

PMID- 11952439
TI  - Dynamic cerebral autoregulation in healthy adolescents.
AB  - BACKGROUND: : There is little information on the limits of cerebral
      autoregulation and the autoregulatory capacity in children. The aim of this study
      was to compare dynamic cerebral autoregulation between healthy adolescents and
      adults. METHODS: : Seventeen healthy volunteers 12-17 years (n = 8) and 25-45
      years (n = 9) were enrolled in this study. Bilateral mean middle cerebral artery
      flow velocities (Vmca; (cm/s)) were measured using transcranial Doppler
      ultrasonography (TCD). Mean arterial blood pressure (MAP) and end-tidal carbon
      dioxide were measured continuously during dynamic cerebral autoregulation
      studies. Blood pressure cuffs were placed around both thighs and inflated to 30
      mmHg above the systolic blood pressure for 3 min and then rapidly deflated,
      resulting in transient systemic hypotension. The change of Vmca to change in MAP
      constitutes the autoregulatory response, and the speed of this response was
      quantified using computer model parameter estimation. The dynamic autoregulatory
      index (ARI) was averaged between the two sides. RESULTS: : Adolescents had
      significantly lower ARI (3.9 +/- 2.1 vs. 5.3 +/- 0.8; P=0.05), and higher Vmca
      (75.2 +/- 15.2 vs. 57.6 +/- 15.0; P<0.001) than adults. CONCLUSION: : The
      autoregulatory index is physiologically lower in normal adolescents 12-17 years
      of age than in adults.

PMID- 11952440
TI  - Procalcitonin and neopterin as indicators of infection in critically ill
      patients.
AB  - BACKGROUND: : In critically ill patients, severe infection and systemic
      inflammation due to non-infectious causes produce very similar clinical
      presentations, and traditional infection markers do not always differentiate
      these two conditions. Both procalcitonin and neopterin have been suggested to aid
      in the early diagnosis of bacterial infections and in differentiating bacterial
      infections from systemic inflammatory, non-infectious diseases or from viral
      infections. METHODS: : Procalcitonin (PCT) and neopterin were analyzed in 208 ICU
      patients who developed acute fever or septic shock. Blood samples were taken
      every 8th h within 48 h of the onset of fever or septic shock. RESULTS: : A total
      162/208 of patients had infection, the most common location being the respiratory
      tract. Mortality was higher in infected patients (31.4% vs. 10.9%; P < 0.01). The
      optimum cut-off levels in identifying patients with infection of daily peak PCT
      were 0.8 microg/L on day 1 and 0.9 microg/L on day 2, and both sensitivity (67.7%
      and 60.9%, respectively) and specificity (47.8% and 63%) were poor. Accordingly,
      the optimum cut-off values of peak neopterin were 18 and 16 pg/L. The sensitivity
      was 62.7% on day 1 and 69.3% on day 2, while specificity was correspondingly
      78.3% and 67.9%. There were no significant differences between the markers in
      discriminating between patients with infection or inflammation. Both PCT and
      neopterin increased with the severity of infection. They were higher in non
      survivors. CONCLUSION: : PCT and neopterin were equally effective, although not
      very accurate in differentiating between infection and inflammation in critically
      ill patients. Neopterin was more specific than PCT, suggesting that neopterin is
      related to the activity of inflammatory response.

PMID- 11952441
TI  - Influence of surgery and endotoxin-induced sepsis combined on natural killer cell
      activity, oxidative burst of granulocytes and antigen presentation capability of
      monocytes.
AB  - BACKGROUND: Cell mediated immunity is affected in the course of sepsis and
      following surgical stress. The natural killer (NK) cells, the granulocytes and
      the monocytes constitute the immediate unspecific cell mediated immunity. We
      therefore investigated the effect of surgery- and endotoxin-induced sepsis on NK
      cells, granulocytes and monocytes in a two-hit model. METHODS: Three groups of 40
      mice. Each group was divided into four groups of 10 mice. All the animals were
      anesthetized and subjected to either: laparotomy; treatment with Escherichia coli
      endotoxin i.p.; laparotomy followed 20 min later by endotoxin i.p.; or left
      untreated as a control group. In the first 40 mice the NK cell activity in the
      spleen and number of NK cells in the liver were measured, in the second the
      oxidative burst of granulocytes, and in the third the antigen presentation
      capacity of monocytes. RESULTS: Endotoxin stimulated the NK cell activity and up
      regulated the antigen presentation capability on monocytes. In contrast, surgical
      stress reduced the NK cell activity, the number of NK cells and down-regulated
      the antigen presentation capability on monocytes. After surgery, followed by
      administration of endotoxin, the oxidative burst of granulocytes was stimulated
      while antigen presentation capability on monocytes was down-regulated. Endotoxin
      prevented or reverted the postoperative suppression of NK cell activity.
      CONCLUSION: Our two-hit model shows that some cell types of the unspecific immune
      system exhibit an excessive inflammatory response (NK cells, granulocytes) while
      specific functions of other cell types (monocytes) are simultaneously diminished.
      This diversity makes a potential therapeutic immunomodulation very complex as
      some cell types would need to be down-regulated while others need to be
      stimulated.

PMID- 11952442
TI  - Sentinel node mapping affects intraoperative pulse oximetric recordings during
      breast cancer surgery.
AB  - BACKGROUND: In invasive breast cancer lymphatic mapping with patent blue vital
      dye (PBV) is used intraoperatively to identify the sentinel lymph nodes: the
      first axillary node draining the mammary lymphatic basin and first involved by
      the metastatic growth in breast cancer. Patent blue vital dye spreads to tissues
      giving a bluish tinge to patients. We have noted the possibility that
      intraoperative peripheral pulse oximetric (SpO2) values are artificially low when
      intradermal PBV is used. METHODS: Twenty patients with normal pulmonary function
      undergoing breast cancer surgery in standardized anesthesia either did or did not
      receive intradermal PBV sentinel node marking. The radial artery was cannulated
      for blood-gas-analysis; arterial oxygen tension (PaO2); and arterial oxygen
      saturation (SaO2). Peripheral oxygen saturation was measured using the light
      absorption technique. Red and infrared light (660 and 900 nm), used by
      pulseoxymetry, is partially absorbed when passing through the tissue. The amount
      of light absorbed is sensed and saturation calculated. The color of the skin was
      evaluated. RESULTS: Peripheral oxygen saturation decreased only immediately after
      the injection of PBV, and remained at a significantly lower level (P<0.001)
      throughout the operation and up to 90 min postoperatively. Arterial oxygen
      tension and SaO2 values did not decrease after intradermal PBV. Patent blue vital
      dye made patients' skin more bluish (P<0.001). No changes in SpO2, PaO2 and SaO2
      were found in control patients. CONCLUSION: The spectrum of PBV has a peak
      absorption at 640 nm, thus making the SpO2 values incorrect. Peripheral oxygen
      saturation values are falsely low and true arterial oxygenation is not impaired
      when PBV is used during sentinel node mapping.

PMID- 11952443
TI  - Development and evaluation of a video program for presentation prior to elective
      cardiac surgery.
AB  - BACKGROUND: : The objective of the present study was to develop and evaluate the
      effects of a preparatory videotape on endocrine stress responses of patients
      prior to cardiac surgery and to analyze patient acceptance of this video for
      preoperative preparation. METHODS: : 101 male patients prior to elective cardiac
      surgery were enrolled into the study. On the day before surgery, patients were
      assigned to one of the following groups: group 1 (n = 51) saw a video with
      realistic information about the upcoming perioperative procedure, and group 2 (n
      = 50) saw a video of the same length without surgery-related information. Venous
      blood was sampled before and 15 min after the video presentation. On the second
      postoperative day, patients filled in a questionnaire concerning their
      experiences of having preoperatively watched the video. RESULTS: : After viewing
      the video, blood levels of cortisol, adrenocorticotropic hormone (ACTH), beta
      endorphin, prolactin, epinephrine and norepinephrine in patients of group 1 were
      not significantly different compared to values measured before the video
      presentation. In patients of group 2, blood levels of cortisol, ACTH, prolactin
      and norepinephrine were significantly lower after video presentation compared to
      values obtained before the video. Patients of group 1 (compared to group 2) were
      significantly more often of the opinion that the video had helped in the
      preparation for surgery, and that they would like to repeat this adjunct
      preoperative video preparation in another similar situation. CONCLUSION: : We
      conclude from our results that (i); cardiac surgical patients prefer
      preoperatively an adjunct surgery-related video preparation to a non-specific
      video presentation, and that (ii); preoperative preparation with realistic
      information about the upcoming medical procedure in patients undergoing cardiac
      surgery does not lead to an increase in endocrine stress hormone levels.

PMID- 11952444
TI  - Pulse contour analysis versus thermodilution in cardiac surgery patients.
AB  - BACKGROUND: Previous studies have demonstrated that there is a lack of agreement
      between intermittent cold bolus thermodilution (ICO) and a semicontinuous method
      with dilution of heat (CCO) in cardiac surgical patients following hypothermic
      extracorporeal circulation (HCPB). Therefore, the aim of the present study was to
      compare both ICO and CCO with continuous pulse contour analysis (PCCO): a method
      based on a fundamentally different principle of determining cardiac output (CO).
      METHODS: A prospective criterion standard study of 25 cardiac surgery patients
      undergoing HCPB. Cardiac output was determined using the three methods (ICO, CCO,
      and PCCO) before and after HCPB up to 12 h after arrival on the ICU. Bias and
      precision were evaluated. RESULTS: A total of 380 triple determinations of CO
      could be analyzed. During the entire study period bias PCCO-ICO was -0.14 l*/min
      (precision 1.16 l*/min) and bias CCO-ICO was -0.40 l*/min (precision 1.25
      l*/min). Up to 45 min after bypass PCCO agreed with ICO (bias -0.21 l*/min,
      precision 1.37 l*/min), while bias CCO-ICO was -1.30 l*/min (precision 1.45
      l*/min). CONCLUSION: The agreement between PCCO and ICO in contrast to CCO in the
      first 45 min after HCPB indicates that CCO underestimates CO during this period.

PMID- 11952445
TI  - Rectally administered diclofenac (Voltaren) reduces vomiting compared with opioid
      (morphine) after strabismus surgery in children.
AB  - BACKGROUND: Nausea, vomiting and pain are common complications after strabismus
      surgery in children. Diclofenac, a non-steroid anti-inflammatory drug, is widely
      used to treat acute and chronic pain but there are few reports of its use given
      rectally in children undergoing strabismus surgery. This open randomised study
      was designed to investigate the analgesic and anti-emetic properties of rectally
      administered diclofenac compared with opioid (morphine) given i.v. in connection
      with strabismus surgery in children. METHODS: After obtaining approval from the
      local ethics committee and written informed consent from the parents, 50 ASA
      class I-II children, 4-16 years of age, were randomised to receive either
      rectally administered diclofenac (Voltaren) 1 mg/kg or i.v. opioid (morphine)
      0.05 mg/kg perioperatively. The children were consecutively operated upon from
      May 1999 to January 2001. Anaesthesia was induced with fentanyl and propofol and
      maintained with propofol. Nitrous oxide was omitted. The postoperative pain was
      assessed after arrival at the post anaesthesia care unit (PACU) by using the
      validated Wong and Baker scale (FACES) Pain Rating Scale. Postoperative nausea
      and vomiting (PONV) was assessed by measuring the frequency of vomiting and the
      degree of nausea. RESULTS: In the diclofenac group the incidence of PONV during
      the first 24 h was 12% (of which one child had severe vomiting). The incidence of
      PONV was much higher, 72% (P = 0.0000), in the morphine group, where 56% of the
      children also had severe vomiting. There were no difference in pain score between
      the two groups. Recovery time at the PACU was longer (P < 0.002) and the
      postoperative analgesic requirement higher in the morphine group (10 vs. 5
      children). No children needed overnight admission to the hospital. CONCLUSION:
      Diclofenac given rectally is an effective analgesic for this kind of surgery and
      gives less postoperative nausea than i.v. morphine. No serious adverse events
      were observed.

PMID- 11952446
TI  - Comparison between intra-articular bupivacaine with epinephrine and epinephrine
      alone on short-term and long-term pain after knee arthroscopic surgery under
      general anesthesia in day-surgery patients.
AB  - BACKGROUND: : Postarthroscopy analgesia has been provided with intra-articular
      bupivacaine, but reported results are conflicting regarding efficacy and the
      duration of analgesia. The immediate and long-term effects of intra-articular
      bupivacaine with epinephrine after arthroscopic knee surgery were therefore
      studied in a day surgery setting. METHODS: : 120 ASA I-II patients scheduled for
      arthroscopic knee surgery were given general anesthesia with spontaneous
      breathing via a laryngeal mask. In a randomized and blinded fashion half of them
      received, at the end of surgery, intra-articularly 20 mL 0.5% bupivacaine with
      epinephrine (B + E-group) and the other half 20 mL saline with epinephrine (S + E
      group). All patients received ketoprofen 100 mg i.v. during surgery and another
      100 mg 2-3 h postoperatively. The patients were observed for about 4.5 h in the
      day surgery unit before discharge. RESULTS: : The results showed that in
      comparison with the S + E-group, significantly fewer patients in the B + E-group
      needed analgesics (P < 0.0001) and the amount required was also significantly
      less postoperatively, before discharge (about 4.5 h postoperatively) (P <
      0.0001). The latency to the need for the first postoperative analgesic was
      shorter in the S + E-group patients (P < 0.0001). At home, during seven days
      after discharge, the need for analgesic (oral ketoprofen 100 mg) was greater in
      the B + E-group (P < 0.05), especially only during the second postoperative day,
      but the visual analoque pain scale (VAPS) scores were low with no differences
      between the groups. No complication occurred. CONCLUSION: : It is concluded that
      a good postoperative pain control of intra-articular bupivacaine with epinephrine
      was found only in the immediate postoperative period (i.e. before discharge) in a
      day-surgery arthroscopic knee surgery patients.

PMID- 11952447
TI  - Effect of delayed supine positioning after induction of spinal anaesthesia for
      caesarean section.
AB  - BACKGROUND: The study tested the hypothesis that the incidence of hypotension
      during spinal anaesthesia for caesarean section is less in parturients who remain
      in the sitting position for 3 min compared with parturients who are placed in the
      modified supine position immediately after induction of spinal anesthesia.
      METHODS: Spinal anaesthesia was induced with the woman in the sitting position
      using 2.8 ml hyperbaric bupivacaine 0.5% at the L(3-4) or L(2-3) interspace.
      Ninety-eight patients scheduled for elective caesarean section under spinal
      anaesthesia were randomised to assume the supine position on an operating table
      tilted 10 degrees to the left (modified supine position) immediately after spinal
      injection (group 0, n=52) or to remain in the sitting position for 3 min before
      they also assumed the modified supine position (group 3, n=46). Isotonic saline 2
      300 ml was given intravenously over 15 min before spinal injection followed by 15
      ml/kg over 15-20 min after induction of spinal anaesthesia. If the systolic blood
      pressure decreased to less than 70% of baseline or to less than 100 mmHg or if
      there was any complaint of nausea, ephedrine was given in 5 mg boluses
      intravenously every 2 min. RESULTS: The blood pressure decreased significantly in
      both groups following spinal injection (P<0.001). Blood pressure variations over
      time differed significantly between the two groups (P<0.05). However, the
      incidence of maternal hypotension before delivery was similar in the two groups.
      The difference was caused by the time to the blood pressure nadir being
      significantly shorter in group 0 compared with group 3 (9.1+/-4.5 min vs. 11.7+/
      3.7 min, P<0.01). Similar numbers of patients received rescue with ephedrine
      before delivery: 35 (67%) in group 0 vs. 26 (57%) in group 3 (NS). The mean total
      dose of ephedrine before delivery was 10.9 mg in group 0 vs. 9.2 mg in group 3
      (NS). There were no differences in neonatal outcome between the two groups.
      CONCLUSION: At elective caesarean section, a 3-min delay before supine
      positioning does not influence the incidence of maternal hypotension after
      induction of spinal anaesthesia in the sitting position with 2.8 ml of
      bupivacaine 0.5% with 8% dextrose.

PMID- 11952448
TI  - Interrater reliability of diagnosing complex regional pain syndrome type I.
AB  - BACKGROUND: Diagnosis of complex regional pain syndrome type I (CRPS I) is based
      on clinical observation of symptoms. As little information is available on the
      reliability of CRPS I diagnosis, we evaluated the agreement between therapists
      with regard to the presence and severity of CRPS I and its symptoms. METHODS: The
      interrater reliability was evaluated in 37 presumed CRPS I patients by three
      observers; one consultant anesthesiologist and two resident anesthesiologists.
      Patients were assessed on the basis of Veldman's CRPS criteria. RESULTS: The
      interrater reliability for diagnosing CRPS I was good for the majority of
      observer combinations. The percentage of agreement for the absence or presence of
      CRPS I was good (88%-100%). Cohen's Kappa's ranged from 0.60 to 0.86. The
      agreement for the mean symptom score ranged from 70.2% to 88.6%; Kappa's were
      lower and showed more variation. Interrater reliability for assessment of the
      severity of CRPS I and its symptoms was poor. Factors influencing the interrater
      reliability were symptom type, individual observers and sample population.
      CONCLUSION: Diagnosing CRPS I can be performed on the basis of clinical
      observation. Further assessment of severity of CRPS I and its symptoms should be
      performed with reliable and valid measurement instruments.

PMID- 11952449
TI  - The importance of tail temperature monitoring during tail-flick test in
      evaluating the antinociceptive action of volatile anesthetics.
AB  - BACKGROUND: Tail-flick (TF) latency can be influenced by tail-skin temperature
      (TT), and treatments that raise TT can mimic hyperalgesia on a TF test. As
      volatile anesthetics can raise TT via heat redistribution, their antinociceptive
      action can be hidden or obscured in a TF test. We tested the hypothesis that TT
      monitoring improves the efficiency of TF tests in evaluating the antinociceptive
      action of volatile anesthetics. METHODS: The relationship between TT and TF
      latency was first explored under varied TTs in 12 rats. Then, TT and TF latency
      were measured before and during isoflurane exposure (1.2%). In the low
      temperature group (n=6), rats were prewarmed mildly to increase TT during
      isoflurane exposure. In the high temperature group (n=6), rats were prewarmed
      enough to prevent a TT increase during isoflurane exposure. RESULTS: There was a
      highly significant correlation between TT and TF latency, that is, TF latency
      decreased as TT increased. In the low temperature group, there was a significant
      increase in TT during isoflurane exposure, while an increase in TF latency did
      not reach statistical significance. Tail-flick latency corrected by a change in
      TT showed a significant increase. In the high temperature group, TF latency
      increased significantly during isoflurane exposure without an increase in TT.
      CONCLUSIONS: Isoflurane inhalation can induce an increase in TT, which can
      obscure its antinociceptive action as evaluated by a TF test. Monitoring TT
      during a TF test is important to efficiently evaluate the antinociceptive action
      of volatile anesthetics.

PMID- 11952450
TI  - Rapid detection of oesophageal intubation: take care when using colorimetric
      capnometry.
AB  - BACKGROUND: Rapid detection of a misplaced endotracheal tube in the esophagus is
      crucial, especially in emergency situations. Hence, we have compared the ability
      of a colorimetric CO2 indicator (Colibri technology, CO2ntrol 1) and a
      capnography to differentiate oesophageal and tracheal intubation, with and
      without CO2 air in the esophagus. METHODS: Fourteen otherwise healthy patients
      were intubated with an endotracheal tube in the trachea under general anesthesia.
      After a positive verification of this endotracheal tube and established
      mechanical ventilation a second endotracheal tube was placed in the esophagus.
      Both were initially ventilated four times, and expired CO2 was measured with a
      mainstream capnograph and a colorimetric indicator. In the remaining five
      patients CO2 containing air was inserted into the esophagus first and then
      ventilated four times. RESULTS: Both the colorimetric indicator and mainstream
      capnograph verified correct placement of the endotracheal tube from the first
      ventilation. When the tube was placed in the esophagus, both methods correctly
      showed that no CO2 was present. However, in patients (n=5) with CO2 installed in
      their esophagus, the colorimetric indicator, but not the capnograph, had readings
      showing that CO2 was present. This may cause a misinterpretation of correct
      tracheal placement. CONCLUSIONS: We found that in emergency situations where CO2
      containing air may be present in the esophagus, capnography should be the
      preferred method of verifying endotracheal and not oesophageal intubation. The
      tested colorimetric CO2 indicator (Colibri technology, CO2ntrol 1) is very
      sensitive to low CO2 values. It may therefore falsely indicate correct
      endotracheal intubation, even when the tube is in the oesophageus.

PMID- 11952451
TI  - In-hospital cardiopulmonary resuscitation: organization, management and training
      in hospitals of different levels of care.
AB  - BACKGROUND: : During recent years in-hospital cardiopulmonary resuscitation (CPR)
      management has received much attention. This can be attributed to the Utstein
      model for in-hospital CPR developed in 1997. The present status of in-hospital
      resuscitation management in Finnish hospitals is not known. Therefore, a study
      was designed to describe the organization of training and clinical management of
      CPR in Finnish hospitals of different levels of care. METHODS: : In the summer of
      2000, we performed a cross-sectional mail survey throughout Finland, including
      all district, central and university hospitals. The questionnaire outlined in
      detail in-hospital resuscitation management and training. For analysis the
      hospitals were divided into primary, secondary and tertiary groups, depending on
      levels of care. RESULTS: : Most hospitals (72%) reported having a physician or a
      nurse in charge of resuscitation management and training. Training in advanced
      life support was more common among nurses (80%) than among physicians (53%).
      Surprisingly, a majority of respondents (75%) reported that they felt training in
      CPR was insufficient. On the general wards and on wards treating cardiac
      patients, defibrillation was in most cases performed by a physician (91% and 51%,
      respectively), and less often by a nurse (16% and 31%, respectively). In the
      secondary and tertiary hospitals cardiac arrest was managed by a cardiac arrest
      team (53% and 62%, respectively) and in the primary hospitals by the ward
      physician (56%), anesthesiologist or emergency physician on call (44%). Most
      hospitals used do-not-resuscitate orders (83%) but only 33% of the hospitals had
      a unified style of notation. Systematic data collection was practised in 55% of
      hospitals, predominantly by using a model of their own. Only a few hospitals
      (11%) used the in-hospital Utstein model. CONCLUSION: : Our study showed that
      more attention needs to be paid to CPR management in Finnish hospitals. At
      present, 25% of hospitals do not have an appointed physician or nurse in charge
      of organizing CPR management. The study also revealed a lack of regular organized
      training in resuscitation for physicians. Fifty-five per cent of hospitals
      practise systematic data collection, but only 11% according to the Utstein
      template; and without which further quality assurance is difficult.

PMID- 11952453
TI  - Post-operative paraplegia following spinal cord infarction.
AB  - Thoracic epidural analgesia is a frequently utilised technique. Neurological
      complications are uncommon, but of grave consequence with significant morbidity.
      Spinal cord infarction following epidural anaesthesia is rare. We present a case
      where a hypertensive patient underwent an elective sigmoid colectomy under
      combined general/epidural anaesthesia for a suspected malignant abdominal mass.
      An epidural infusion was used for intra-operative and post-operative analgesia.
      During surgery, the blood pressure was labile and she was hypotensive.
      Postoperatively, the patient became confused, pyrexial and tachycardic and
      developed systemic inflammatory response syndrome requiring intensive care
      management. She developed a flaccid paralysis at L3 level with areflexia,
      analgesia and impaired sensation. A spinal cord infarct in the region of the
      conus extending into the thoracic cord was diagnosed. Complications of epidural
      anaesthesia are easily recognised when they develop immediately; their
      relationship to the anaesthesia and the post-operative period may be misjudged or
      underestimated when they appear after a delay, if neurological signs are masked
      by lack of patient cooperation and drowsiness or if the epidural anaesthesia is
      prolonged by long-acting drugs. New neurological deficits should be evaluated
      promptly to document the evolving neurological status and further testing or
      intervention should be arranged if appropriate. The association with epidural
      anaesthesia as a cause of paraplegia is reviewed. The aetiological factors that
      may have contributed to this tragic neurological complication are discussed.

PMID- 11952452
TI  - Appropriateness of leaving emergency medical service treated hypoglycemic
      patients at home: a retrospective study.
AB  - BACKGROUND: Hypoglycemic patients treated by the emergency medical service (EMS)
      system are commonly left home. The criteria for leaving hypoglycemic patients at
      home and the appropriateness of the procedure remains, however, unvalidated. The
      present retrospective article addresses these questions. METHODS: The Copenhagen
      physician-based mobile intensive care unit (MICU) responds to emergency calls in
      a two-tier rendezvous system. Its prehospital data from 1995 to 1998 were
      retrospectively incorporated into a clinical database and cross-referenced with
      clinical information from three Danish national registries, enabling
      identification of criteria for transportation of the patients to the hospital,
      and a detailed 72-h follow up on patients left at home. RESULTS: The MICU treated
      1148 hypoglycemic patients within the period, of which 84% were released at home.
      Treatment or no treatment before arrival of the MICU and level of consciousness
      following MICU treatment, were found to be strong predictors of a need for
      transportation to hospital; although other factors were implicated. Within the 72
      h following MICU treatment less than 8% of the patients left at home needed
      secondary MICU or hospital treatment because of glucose regulatory problems, and
      less than 5% experienced secondary hypoglycemia. Less than 1% was admitted to
      hospital beds with recurrent hypoglycemia within 24 h. Poor compliance with the
      diabetic treatment instructions often appeared to be involved in cases of
      recurrent hypoglycemia. A delay in admission was not to blame for a serious
      secondary patient course in any of the cases. CONCLUSION: The majority of
      patients with prehospital hypoglycemia may safely be treated and released at home
      in a physician-based EMS area.

PMID- 11952454
TI  - Use of remifentanil for awake fiberoptic intubation in a morbidly obese patient
      with severe inflammation of the neck.
AB  - Impending upper airway obstruction due to odontogenic facial and cervical
      spreading infection is a potential fatal situation that requires urgent
      treatment. In particular, securing the threatened airway is a priority and a
      precondition to the pressing need for surgery. The best approach to establish the
      difficult airway is awake fiberoptic intubation or scheduled tracheotomy under
      local anesthesia. We report a critical case of severe swelling of the neck in a
      morbidly obese patient with no alternative to awake fiberoptic intubation. The
      primary goals of optimal safety for the patient and appropriate intubating
      conditions for the anesthesiologist made us to consider a new method of patient
      medication.

PMID- 11952455
TI  - What is quality in maternity care? An international perspective.
AB  - This paper delineates important considerations for having a better understanding
      of quality in maternity care. High quality requires providing a minimum level of
      care to all pregnant women and their new born babies and a higher level of care
      to those who need it; obtaining the best possible medical outcome of mother and
      baby; providing care which satisfies users and providers; and maintaining sound
      managerial and financial performance. While all these aspects are important,
      prioritizing among interventions to improve them will be influenced by cultural
      values, expectations and available resources.

PMID- 11952456
TI  - Diagnostic evaluation of intrauterine fetal deaths in Stockholm 1998-99.
AB  - BACKGROUND: To evaluate the diagnostic methods and to elucidate the etiology of
      intrauterine fetal death. MATERIAL AND METHODS: A prospective study was conducted
      on all intrauterine fetal deaths occurring in Stockholm County in 1998-99. During
      a 24-month period, 188 cases of intrauterine fetal death with gestational ages of
      > or = 22 weeks were investigated in accordance with structured test protocol.
      All information from antenatal and delivery records as well as all test results
      were entered in to an Internet-based database for continuous evaluation. RESULTS:
      A presumptive explanation to the stillbirth was established in 91% of the cases.
      The most common factors associated with intrauterine fetal death could be
      identified as infections (24%), placental insufficiency/intrauterine growth
      restriction (22%), placental abruption (19%), intercurrent maternal conditions
      (12%), congenital malformations (10%), and umbilical cord complications (9%).
      CONCLUSIONS: A relevant test protocol in cases of intrauterine fetal death
      reduces the number of unexplained cases to a minimum. An Internet-based register
      on test results of fetal deaths may enable a continuous evaluation of the
      diagnostic tools and etiologic factors in an ever-changing panorama. The results
      from the present study can serve as a base for a case-control study in Sweden.

PMID- 11952457
TI  - Pregnancy and the Ehlers-Danlos syndrome: a retrospective study in a Dutch
      population.
AB  - BACKGROUND: The study was carried out to assess the course and outcome of
      pregnancies in women with the Ehlers-Danlos syndrome, with the aim of developing
      guidelines for assessment of risk and counseling, and for providing optimum
      medical and obstetric care. METHODS: A retrospective study based on data
      collected from members of the Dutch Association of Ehlers-Danlos patients.
      Pregnancies and neonatal outcomes of the affected mothers were compared with
      those of the nonaffected mothers who delivered an infant with Ehlers-Danlos
      syndrome. RESULTS: In a group of 46 women with Ehlers-Danlos syndrome, 128
      pregnancies beyond 24 weeks gestation were evaluated and compared with 43
      pregnancies of 33 nonaffected women. The main maternal complications consisted of
      pelvic pain and instability (26% vs. 7%). One bowel rupture was reported in a
      woman with Ehlers-Danlos syndrome type IV. Preterm delivery occurred in 21% of
      the affected mothers compared with 40% of the nonaffected women with an affected
      infant; the women with Ehlers-Danlos syndrome experienced postpartum hemorrhage
      (19% vs. 7%) and complicated perineal wounds (8% vs. 0%) more often than the
      unaffected women. The floppy infant syndrome was diagnosed in 13% of the affected
      infants and did not occur in the nonaffected neonates. CONCLUSION: Pregnancy is
      generally well-tolerated in women with Ehlers-Danlos syndrome, with favorable
      maternal and neonatal outcomes. In Ehlers-Danlos syndrome type IV it may be
      associated with severe maternal complications. Preconceptional counseling
      concerning specific possible complications and a multidisciplinary approach are
      recommended.

PMID- 11952458
TI  - Maternal mortality in northern rural Tanzania: assessing the completeness of
      various information sources.
AB  - BACKGROUND: To assess the completeness of various information sources and the
      subsequent estimates on maternal mortality. METHODS: Maternal deaths in the study
      area, rural northern Tanzania, in 1995 were identified from hospital records,
      health centers and dispensaries, registration by village leaders, follow up of an
      antenatal cohort, and a household survey. Data from some of these sources were
      also obtained in 1996. RESULTS: In 1995, 22 of a total of 26 maternal deaths were
      identified at the Haydom hospital. Three of the 15 deaths (20%) reported by the
      village leaders were not identified at any health facility. Four deaths were
      found in the antenatal cohort and one death in the household survey. Only two
      deaths were reported by the official statistics. Of the identified maternal
      deaths, 85% were found from health facility data. Including data from 1996, a
      total of 45 maternal deaths were identified; 13 of which were direct and 32
      indirect obstetric deaths. The 1995 estimated maternal mortality ratio, based on
      reports from the multiple source registrations, was 382 (95% confidence interval
      250-560) per 100 000 live births. The antenatal cohort yielded an estimate of 322
      (95% confidence interval 160-580). The ratio based on official figures for 1995
      and 1996 combined was 123 (95% confidence interval 70-200). CONCLUSIONS: Even a
      high quality routine registration of maternal deaths will miss a small proportion
      of cases. Investing in better registration of direct and indirect obstetric
      deaths will give better insight into this important health problem. Estimates
      based on official reports showed substantial underreporting.

PMID- 11952459
TI  - Urinary heparan sulfate proteoglycan excretion in black African women with pre
      eclampsia.
AB  - BACKGROUND: The heparan sulfate proteoglycan of the glomerular basement membrane
      is considered to be mainly responsible for the charge selectivity of the
      glomerular basement membrane. Decreased heparan sulfate proteoglycan results in a
      decreased anionic charge of the glomerular basement membrane with increased
      heparan sulfate proteoglycan in the urine, and is believed to be responsible for
      the proteinuria in pre-eclampsia. AIM: To determine the urinary heparan and
      chondroitin sulfate proteoglycan levels in women with pre-eclampsia. MATERIALS
      AND METHODS: Eighty-four patients were studied: 28 were normotensive pregnant, 28
      were nonproteinuric hypertensive, and 28 were pre-eclamptic. Urine samples were
      obtained and urinary glycosaminoglycan concentrations were determined using the
      dimethyl-methylene blue assay. Plotting absorbance against the concentrations of
      heparan and chondroitin sulfate proteoglycans drew a standard curve. The
      concentration of heparan and chondroitin sulfate proteoglycans was read-off from
      the linear portion of the standard curve. The standard solutions contained 25,
      50, 100 and 200 mg/l heparan or chondroitin sulfate. The Mann-Whitney U-test was
      used to detect differences between the three groups, and the Pearson's
      correlation coefficient was calculated for clinical data correlation of the pre
      eclamptic group. RESULTS: Urinary excretion of heparan sulfate proteoglycan
      (123.1 +/- 22.1 mg/l) was significantly increased in the pre-eclamptic group
      compared with the normotensive pregnant group (60.5 +/- 5.1 mg/l; p < 0.0001) and
      the hypertensive nonproteinuric group (63. 2 +/- 3.7 mg/l; p < 0.0001). Urinary
      chondroitin sulfate proteoglycan excretion followed a similar pattern, being
      significantly increased in the pre-eclamptic group (88.86 +/- 9.79 mg/l) compared
      with the normotensive pregnant group (49.1 +/- 8.49 mg/l; p < 0.0001) and the
      hypertensive nonproteinuric group (43. 9 +/- 5.7 mg/l; p < 0.0001). A significant
      Pearson's correlation between 24-h urine output vs. 24-h protein excretion (r =
      0.51; p < 0.001), and between loss of HSPG versus 24-h urinary protein excretion
      (r = 0.72; p < 0.0001) was obtained in the pre-eclamptic group. CONCLUSION: This
      study demonstrates a reduction of glomerular charge in pre-eclampsia. The strong
      correlation between the severity of proteinuria and the loss of charge supports
      the hypothesis that the loss of glomerular charge induces structural changes of
      the filtration barrier, and may be the mechanism responsible for the proteinuria
      in pre-eclampsia. Furthermore, the elevated levels of urinary proteoglycan
      (heparan and chondroitin sulfate proteoglycans) in this disorder show a loss into
      the urine rather than a neutralization of these macromolecules.

PMID- 11952460
TI  - Risk factors for cesarean section of primiparous women aged over 35 years.
AB  - BACKGROUND: To determine the perinatal outcome of pregnancy in primiparous women
      over 35 years of age and to evaluate determinants predicting cesarean delivery in
      these women. METHODS: Two hundred and seven mothers aged at least 35 years (1.8%
      of the total deliveries) delivered in the Department of Obstetrics and Gynecology
      between 1995 and 2000. These women were matched with women aged 20-29 years
      according to gravidity. Multiple logistic regression analysis was used to
      evaluate the risk of cesarean delivery, with controls for possible confounding
      factors. RESULTS: Cesarean section was 2.09-fold more prevalent among the older
      than among the younger women; the difference being significant (odds ratio,
      OR=3.36, 95%CI 2.22-5.09; p<0.001). The advanced maternal age was associated with
      a significantly higher rate of assisted reproductive techniques involvement (OR
      6.54; 95%CI 3.54-12.38; p<0.001). The difference between the rates of
      preeclampsia in the two groups did not reach the level of significance (OR 1.85;
      95%CI 1.02-3.34; p=0.056). There were no significant differences in perinatal
      outcome between the two groups. The logistic regression model demonstrated an
      increased risk of cesarean section among the primiparous women aged over 35
      years. CONCLUSIONS: The risk of cesarean section at this advanced age is 6.54
      fold. The determinants are included in the pregnancy, delivery and neonatal
      outcome.

PMID- 11952461
TI  - Perinatal complications among ethnic Somalis in Norway.
AB  - BACKGROUND: The majority of ethnic Somali women in Norway have undergone an
      elaborate form of circumcision (infibulation). The aim of this study was to
      examine the risk of perinatal complications among ethnic Somalis and to discuss
      its relation to circumcision. METHODS: We conducted a cross-sectional population
      based registry study. Data on all births to women born in Somalia (1733) and
      Norway (702 192) from 1986 to 1998 was provided from the Medical Birth Registry
      of Norway. We analyzed the risk of perinatal complications among women of Somali
      origin vs. ethnic Norwegians using univariate and multivariate methods. RESULTS:
      Perinatal complications were more frequent among women of Somali origin than
      among ethnic Norwegians. These included induction of labor, fetal distress,
      secondary arrest, prolonged second stage of labor, operative delivery and
      perinatal death. Particularly elevated odds ratios were found for fetal distress
      (odds ratio=2.6, 95% confidence interval (CI); 2.2-3.0), emergency cesarean
      sections (odds ratio=3.0, 95% confidence interval 2.6-3.4), Apgar scores below
      seven (odds ratio = 3.1, 95% confidence interval 2.4-4.0) and prelabor fetal
      deaths (odds ratio=2.5, 95% confidence interval 1.7-3.7). CONCLUSION: Similar
      findings in infibulated vs. noncircumcised women have been demonstrated
      previously in other studies indicating that circumcision could play a role. The
      current study is the first to be conducted among Somali women in Europe. However,
      the results are not informative on whether the adverse birth outcomes are caused
      by infibulation as such or in combination with suboptimal perinatal care,
      intercurrent diseases and sociocultural factors. Somali women represent a high
      risk group in obstetrics, calling for special attention and care.

PMID- 11952462
TI  - Under-reporting of direct and indirect obstetrical deaths in Austria, 1980-98.
AB  - BACKGROUND: Under-reporting and misclassification of maternal deaths are common,
      even in countries with a high quality of death statistics. The aims of this study
      were to determine to what extent maternal deaths are under-reported in Austria
      and to determine factors that might explain under-reporting. METHODS:
      Confidential enquiries on maternal deaths for the period 1980-98 were linked with
      the official mortality statistics from Statistics Austria. Maternal deaths were
      classified as direct and indirect obstetric deaths. RESULTS: Between 1980 and
      1998 a total of 119 maternal deaths (112 direct and seven indirect obstetric
      deaths) were registered at Statistics Austria. Confidential inquiries into
      maternal deaths accumulated 191 maternal deaths (an additional 43 direct
      obstetric deaths and 29 indirect obstetric deaths). Total under-reporting was 38%
      (95% CI 31-45). Significantly more indirect obstetrical deaths were under
      reported (81%; 95% CI 64-92) than direct obstetrical deaths (28%; 95% CI 21-36).
      CONCLUSIONS: This study demonstrates the shortcomings of official registration of
      maternal deaths. Thus, maternal mortality cannot be seen as a reliable basis for
      health policy decisions.

PMID- 11952463
TI  - Is 24-h sperm motility a useful IVF measure when male infertility is not
      apparent?
AB  - OBJECTIVE: To examine the relationship of 24-h sperm motility between post
      insemination and fertilization in vitro, in a population with no apparent semen
      abnormalities. A retrospective study from July 1998 to June 2000. MATERIAL AND
      METHODS: Four hundred and seventy-one consecutive in-vitro fertilization (IVF)
      cycles for which the primary diagnosis was not male infertility (total motility
      count > 40 x 106) were studied. Linear regression was used to examine the general
      relation between 24-h sperm motility and IVF. The cohort with 0% 24-h motility
      was compared with all other cycles using the t-test and the chi2-test. Test
      quality was assessed using the positive likelihood ratio. RESULTS: Overall
      fertilization was 58 +/- 16%. There were 45/471 cycles (9.5%) with zero
      fertilization. Linear regression of percent fertilization vs. 24-h motility
      showed no relationship (r = 0.01). The cohort with 0% 24-h motility had a lower
      fertilization rate 29 +/- 19% (P = 0.05), and had a higher incidence of no
      fertilization 7/21 (P = 0.01). The positive likelihood ratio was 4.6.
      CONCLUSIONS: Zero 24-h motility indicates occult male infertility, and a positive
      result indicates a fair to good test. Overall there was no relationship between
      sperm survival at 24 h post insemination and fertilization in vitro. However, 0%
      24-h sperm motility was associated with reduced fertilization

PMID- 11952464
TI  - Short-term complications after surgically induced abortions: a register-based
      study of 56 117 abortions.
AB  - BACKGROUND: Performing an induced abortion is a rather simple medical procedure
      which is frequently done and side-effects will have public health implications
      unless they are very rare. We estimated the incidence of side-effects detected
      during the stay at the hospital and 2 weeks after the discharge. We only include
      side-effects reported by clinics or hospitals. METHODS: Altogether 56 117 induced
      abortions performed by public hospitals in Denmark from 1980 to 1994 were
      analyzed in this study. The study combined results from the mandatory reporting
      of side-effects to the National Induced Abortion Registry and all diagnoses
      reported to the Hospital Discharge Registry. RESULTS: Side-effects in the form of
      bleeding, infections or re-evacuation were recorded for about 5%. We found more
      side-effects in teenage women and for abortions performed late in pregnancy. We
      found nothing to indicate that the frequency of side-effects following an
      abortion changed over time. CONCLUSIONS: About 5% have side-effects registered by
      hospitals following an induced abortion. The long-term consequences of this are
      not known.

PMID- 11952465
TI  - A comparison of two dosage regimens of oral misoprostol for labor induction at
      term.
AB  - METHODS: 251 women with indications for labor induction at term were randomised
      to receive either 50 or 100 microgs of oral misoprostol, repeated every 4 h to a
      maximum of 5 doses. Parous women in the higher dose group received 50 microgs as
      their first dose, subsequent doses being 100 microgs. Women who failed to respond
      to the 5 doses of misoprostol had the option of having vaginal PGE2 gel. The
      primary outcome measure was the induction to delivery interval in those who
      delivered vaginally. Patient satisfaction was assessed by postnatal
      questionnaire. RESULTS: The induction to vaginal delivery interval, although
      shorter in the 100 microgs group was not statistically significant (26.8 versus
      33.7 h, mean difference 6.9 h, 95% CI 0.4-13). There were, however, more failed
      inductions with misoprostol in the 50 microgs group (12.7% Vs 4.8%, RR 2.6, 95%
      CI 1.07-6.5). There were no differences in the modes of delivery, number of
      caesarean sections for fetal distress or in the neonatal outcomes in the two
      groups. Most patients, 83% and 92% in the 50 and 100 microgs, respectively, were
      satisfied with their inductions, and 64% of patients would prefer to have the
      inducing agent given orally if they were to have another induction. CONCLUSION:
      Oral misoprostol is effective in inducing labor and seems acceptable to patients.
      Both the 50 and 100 microgs dose regimens have a reasonable safety profile, but
      in view of the higher incidence of failed inductions with the 50 microgs dosage,
      the 100 microgs dose regimen may be the preferred dose regimen.

PMID- 11952466
TI  - Symptomatic venous thromboembolism in Chinese patients after gynecologic surgery:
      incidence and disease pattern.
AB  - BACKGROUND: Venous thromboembolism is a common cause of postoperative morbidity
      and mortality in Caucasian populations, but it is widely believed that this
      complication is rare in Chinese. METHODS: We conducted a retrospective study from
      January 1998 to December 2000. Women with thromboembolic diseases after
      gynecologic surgery were identified and their medical records were reviewed.
      RESULTS: During the study period, thirty-one women were diagnosed as having
      thromboembolic disease after gynecologic surgery. Over the study period, the
      total number of operations was 6077, giving an incidence of 5.10/1000 operations.
      There were two cases of pulmonary embolism and the others had deep vein
      thrombosis of which 90% were limited to calf veins only. The incidences were
      significantly higher in 1999 and 2000 (7.59 and 6.85/1000 operations,
      respectively) than that in 1998 (1.7/1000 operations) (P = 0.015), after a case
      of maternal death due to pulmonary embolism in early 1999. Most cases of
      thromboembolism were diagnosed after major surgery for malignancy (n = 14) or
      benign conditions (n = 12). In the remaining cases, three had evacuation of the
      uterus for retained products of conception and two had laparoscopy for suspected
      ectopic pregnancies. CONCLUSIONS: Thromboembolic disease is not uncommon among
      Chinese women after gynecologic surgery. The incidence is similar to that of the
      Caucasian population, although the sites of vascular occlusion were different.
      The long belief that thromboembolism is rare among Chinese is at least partly due
      to under-diagnosis.

PMID- 11952467
TI  - Does urinary incontinence occurrence depend on the menstrual cycle phase?
AB  - BACKGROUND: The aim was to study an eventual co-variation of menstrual cycle
      progression and urinary incontinence (UI) occurrence in 20-54-year-old-women, who
      have regular menstrual cycles, which are not influenced by exogenous sex
      hormones. METHODS: An age-stratified random sample of of 3900 women, aged 20-59
      years, answered a questionnaire on UI. The present analysis included 821 women,
      who reported regular menstrual cycles un-intervened by sex hormone intake.
      RESULTS: Five percent of the women reported episodes of UI the day before they
      answered the questionnaire. Urinary incontinence was unassociated with menstrual
      cycle characteristics, such as time position from day one in the menstrual cycle,
      presence and amount of bleeding and the number of sanitary towels or tampons
      used. There was however, a borderline significant association (P = 0.08) with day
      11-15 before the expected next menstrual bleeding. CONCLUSIONS: The present data
      allow for limited co-variation, if any, to exist in UI occurrence with the
      natural menstrual cycle phases, including the menstruation itself. A hypothesis
      of a moderate UI increase associated with ovulation however, merits attention.

PMID- 11952468
TI  - Recurrent cervical cancer: detection and prognosis.
AB  - BACKGROUND: Only a small proportion of cervical cancer recurrences is detected
      during routine follow-up. We investigated which percentage of recurrences is
      detected during follow-up, which diagnostic tools are helpful to detect recurrent
      disease and which factors are of prognostic significance once recurrent disease
      has been established in patients treated for cervical cancer stage IB-IVA.
      METHODS: Characteristics of the primary tumor, characteristics of recurrent
      disease and follow-up were collected retrospectively from clinical records of 277
      patients who achieved a complete remission of at least 3 months after primary
      treatment for cervical cancer in 1992, 1993 and 1994 in three university
      hospitals in the Netherlands. RESULTS: Of 277 patients, 47 (17%) developed
      recurrent disease; this was most often detected after self-referral (45%), and in
      32% during routine follow-up. Survival did not differ significantly between these
      two groups. The presence of symptoms (87%) was the most important first abnormal
      test result leading to diagnosis of recurrence. In univariate analysis, disease
      free interval (DFI) and treatment modality were significant prognostic factors
      for crude survival of recurrence. However, treatment modality varied considerably
      and the subgroups were small. Therefore, multivariate analysis was not feasible
      and clinically valid conclusions could not be drawn. CONCLUSIONS: In only 32% of
      all cases, recurrence was detected during a scheduled follow-up visit. In the
      majority of patients, recurrent cervical cancer was detected by symptoms (87%).
      In recurrent disease, DFI was a prognostic factor for survival.

PMID- 11952469
TI  - Gestational trophoblastic disease: one more risk in adolescent pregnancy.
AB  - BACKGROUND: An evaluation of the performance of a Referral Center in the
      diagnosis, treatment and follow up of adolescents with gestational trophoblastic
      disease. METHODS: In a 13-year prospective cohort study, between March 1987 and
      March 2000, 124 adolescents with gestational trophoblastic disease were followed
      up and/or treated by a multidisciplinary team. Adolescents underwent strict
      clinical and laboratory control after mole evacuation to guarantee adhesion to
      follow up, early diagnosis, and prompt treatment of persistent disease. The
      Student-Fischer t-test and the chi-square test were used for the statistic
      analysis of the results. RESULTS: Adolescents represented 21.3% of the 583
      patients with gestational trophoblastic disease: 102 (82.3%) had uncomplicated
      hydatidiform moles, and 22 (17.7%) underwent chemotherapy for persistent
      gestational trophoblastic disease or a gestational trophoblastic tumor.
      Complications were diagnosed earlier (p < 0.001) in patients managed and treated
      at the referral center. Of the adolescents with complications, 81.8% were low
      risk, 54.5% were at the International Federation of Gynecology and Obstetrics
      stage I, and 90.9% were treated with chemotherapy only. Time to remission and
      follow up were shorter for uncomplicated hydatidiform moles (9.8 +/- 3.4 weeks
      and 8.8 +/- 1.8 months, respectively) than for persistent disease (16.2 +/- 5.8
      weeks and 45 +/- 24.5 months, respectively). Adhesion to follow up was similar in
      the two groups (84.2% and 91.8%). To this date, 50% of the adolescents have had
      one or more gestations, and 82% of these pregnancies were normal. CONCLUSIONS:
      Adolescents comprise approximately 20% of all gestational trophoblastic disease
      patients and have high adhesion to follow up. The disease did not affect their
      reproductive capacity, and chances of a normal subsequent gestation were high.

PMID- 11952470
TI  - Severe fetomaternal hemorrhage confirmed and quantified by flow cytometry using
      anti fetal hemoglobin antibodies.

PMID- 11952471
TI  - Laparoscopic management of an unrecognized spontaneous bilateral tubal pregnancy.

PMID- 11952472
TI  - Periodic genital pruritus caused by syringoma of the vulva.

PMID- 11952473
TI  - Undescended fallopian tubes and ovaries: a rare incidental finding during an
      infertility investigation work up.

PMID- 11952474
TI  - Ovarian fibrosarcomas.

PMID- 11952476
TI  - On a mission from God: fighting publication bias.

PMID- 11952477
TI  - An evolutionary analysis of the aetiology and pathogenesis of juvenile-onset
      myopia.
AB  - The available evidence suggests that both genes and environment play a crucial
      role in the development of juvenile-onset myopia. When the human visual system is
      examined from an evolutionary perspective, it becomes apparent that humans,
      living in the original environmental niche for which our species is genetically
      adapted (as hunter-gatherers), are either slightly hypermetropic or emmetropic
      and rarely develop myopia. Myopia occurs when novel environmental conditions
      associated with modern civilization are introduced into the hunter-gatherer
      lifestyle. The excessive near work of reading is most frequently cited as the
      main environmental stressor underlying the development of myopia. In this review
      we point out how a previously unrecognized diet-related malady (chronic
      hyperinsulinaemia) may play a key role in the pathogenesis of juvenile-onset
      myopia because of its interaction with hormonal regulation of vitreal chamber
      growth.

PMID- 11952478
TI  - Age-related maculopathy: pathogenetic features and new treatment modalities.
AB  - A considerable amount of new information on putative pathogenetic mechanisms in
      age-related maculopathy and degeneration has emerged in recent years. This
      comprises experimental studies on retinal pigment epithelium (RPE) and rod
      photoreceptor ageing, lipofuscin accumulation, the roles of oxidative stress and
      free radical formation, as well as antioxidants and other defensive mechanisms
      operating against environmental factors and ageing. The current application of
      photodynamic therapy (PDT) using verteporfin marks a new era in the treatment of
      subfoveal classical choroidal neovascularization. Several new treatment
      modalities, such as transpupillary thermotherapy (TTT) and anti-vascular
      endothelial growth factor (VEGF) agents for inhibition of neovascularization,
      have emerged and are undergoing multicentre clinical trials. A period of dynamic
      development in this field has commenced.

PMID- 11952479
TI  - Cyclodextrins in eye drop formulations: enhanced topical delivery of
      corticosteroids to the eye.
AB  - Cyclodextrins are cylindrical oligosaccharides with a lipophilic central cavity
      and hydrophilic outer surface. They can form water-soluble complexes with
      lipophilic drugs, which 'hide' in the cavity. Cyclodextrins can be used to form
      aqueous eye drop solutions with lipophilic drugs, such as steroids and some
      carbonic anhydrase inhibitors. The cyclodextrins increase the water solubility of
      the drug, enhance drug absorption into the eye, improve aqueous stability and
      reduce local irritation. Cyclodextrins are useful excipients in eye drop
      formulations of various drugs, including steroids of any kind, carbonic anhydrase
      inhibitors, pilocarpine, cyclosporins, etc. Their use in ophthalmology has
      already begun and is likely to expand the selection of drugs available as eye
      drops. In this paper we review the properties of cyclodextrins and their
      application in eye drop formulations, of which their use in the formulation of
      dexamethasone eye drops is an example. Cyclodextrins have been used to formulate
      eye drops containing corticosteroids, such as dexamethasone, with levels of
      concentration and ocular absorption which, according to human and animal studies,
      are many times those seen with presently available formulations. Cyclodextrin
      based dexamethasone eye drops are well tolerated in the eye and seem to provide a
      higher degree of bioavailability and clinical efficiency than the steroid eye
      drop formulations presently available. Such formulations offer the possibility of
      once per day application of corticosteroid eye drops after eye surgery, and more
      intensive topical steroid treatment in severe inflammation. While cyclodextrins
      have been known for more than a century, their use in ophthalmology is just
      starting. Cyclodextrins are useful excipients in eye drop formulations for a
      variety of lipophilic drugs. They will facilitate eye drop formulations for drugs
      that otherwise might not be available for topical use, while improving absorption
      and stability and decreasing local irritation.

PMID- 11952480
TI  - John G. Lindberg and the discovery of exfoliation syndrome.
AB  - John G. Lindberg, a young Finnish ophthalmology resident, started a research
      project in 1914 aiming at an academic dissertation. His plan was to elucidate
      Axenfeld's observations on iris changes in senile eyes. Axenfeld had described
      two types of degeneration of the iris: a hyaline degeneration of the iris
      pupillary zone causing poor pupillary dilatation with mydriatics and an atrophy
      of the iris pigment epithelium at the pupillary border. For his research Lindberg
      had to construct a slit-lamp biomicroscope by studying Gullstrand's monograph on
      the matter; slit-lamp biomicroscopes were not commercially available at that
      time. A Sach's lamp was used for transillumination of the iris. While conducting
      his research Lindberg paid attention to greyish flakes and fringes at the
      pupillary border. He also noted how this strange material formed a membrane on
      the anterior lens surface. Documentation was made by skillful hand drawings. The
      new phenomenon was found to be as common in cataract patients as in non
      cataractous controls older than 55 years. The phenomenon was observed in 50% of
      glaucoma patients. Age was the decisive factor; the phenomenon was more prevalent
      with advancing age. Lindberg published his results as a thesis at the University
      of Helsinki in 1917. When attending a Nordic Congress of Ophthalmology in 1921,
      Lindberg met Norwegian ophthalmologist, Birger Malling, and gave him his thesis
      and explained the new findings. In 1920-21 Lindberg worked at Axenfeld's clinic
      in Freiburg, Germany. During this period he met in Basel, Switzerland, a Swiss
      ophthalmologist, Alfred Vogt. He told Vogt about his research and provided him
      with copies of his thesis. Both Malling and Vogt published papers on exfoliation
      in 1923 without referring to Lindberg's work. Lindberg did not, however,
      interfere with these papers. Thus Lindberg was forgotten by his contemporaries as
      a scientist. However, his main conclusions on exfoliation are still valid today.
      The life of this remarkable ophthalmologist is described in the present paper.

PMID- 11952481
TI  - Colour contrast sensitivity in ocular hypertension. A five-year prospective
      study.
AB  - PURPOSE: To evaluate a peripheral colour contrast sensitivity test as a tool for
      early diagnosis of glaucoma in a five-year prospective study. PATIENTS AND
      METHODS: Peripheral colour contrast sensitivity was measured with a computer
      graphics system developed by Arden et al. The test colours were varied along the
      protan, deutan and tritan colour confusion axes on a scale from 0 to 100
      percentage units. Fifty-five ocular hypertensive (OH) patients examined with the
      colour contrast test, stereoscopic photography of the optic discs, and
      measurements of visual fields (Humphrey 24-2 glaucoma hemifield test (GHT)) in
      1994, were re-examined after five years. RESULTS: Ten patients were 'outside
      normal limits' in the GHT at follow-up. This group of 10 patients did not differ
      in colour contrast thresholds at the test in 1994 from the 45 who were still
      'normal' (or 'borderline') at follow-up. Neither were there proportionally more
      patients with GHT 'outside normal values' for the patients with high colour
      contrast thresholds (> 30% units) in 1994 regarding any of the three colour axes.
      As judged from patient files, 27 patients had developed glaucoma during follow
      up. Although there were differences between these 27 glaucoma patients and the
      remaining OH group at the colour contrast test in 1994, these differences did not
      reach statistical significance for any of the colour axes (largest difference in
      the tritan axis: 6.2% units, P = 0.0745). At follow-up, however, there was a
      significant difference in colour contrast for the protan axis between the
      clinical glaucoma group and the OH group (6.7% units, P = 0.0105). CONCLUSION:
      The method used for colour contrast measurement did not reveal glaucomatous
      changes before conventional perimetry (Humphrey 24-2, GHT). Neither did it
      predict the patients who, in our clinic, subsequently developed glaucoma during a
      five-year period. A change over time in colour contrast in the protan axis for an
      OH patient may, however, indicate glaucoma development.

PMID- 11952482
TI  - Screening for amblyopia and strabismus with the Lang II stereo card.
AB  - PURPOSE: To evaluate the effectiveness of the Lang II stereo card as a screening
      test for amblyopia and/or strabismus. METHODS: A total of 1046 children aged 12
      13 years were examined in a field study in the Goteborg area, Sweden. In addition
      to the Lang II stereo card, the examination included visual acuity, cover
      testing, cycloplegic refraction, and inspection of the optical media and
      posterior pole. RESULTS: If every incorrect subject response was considered a
      reason for referral, the Lang II test would have correctly identified 82% (23
      subjects) of the 28 children with manifest strabismus and 38% (11 subjects) of
      the 29 children with amblyopia. The test failed to refer 45% (21 subjects). Of
      all subjects referred, 44 (63%) were found to be ophthalmologically normal.
      CONCLUSIONS: The Lang II stereo card is neither a reliable nor an efficient
      method of screening for amblyopia and/or strabismus.

PMID- 11952483
TI  - Evaluation of the new Ocuton S tonometer.
AB  - PURPOSE: To evaluate the intra- and interobserver variability of the Ocuton S
      tonometer, its correlation with Goldmann tonometry, the reliability of self
      tonometry and the safety of the instrument. METHODS: Thirty-five healthy subjects
      and 45 patients with primary open-angle glaucoma (POAG), aged from 38 to 80 years
      (mean age: 64.6 +/- 12.2 years), underwent tonometry with the Ocuton S tonometer
      in one eye chosen at random. The intra- and interobserver variability between two
      operators (kappa coefficient), the Ocuton S/Goldmann correlation and the
      reliability of self-tonometry were evaluated by performing two tonometries on
      each patient in subgroups. Each tonometry was considered as the mean of three
      consecutive measurements. Central ultrasonic pachymetry, keratometry and corneal
      biomicroscopy were also evaluated. RESULTS: The intra- and interobserver
      variability ranged from 0.38 to 0.66. The difference between the means of
      intraocular pressure (IOP) with the Ocuton S (24.4 +/- 4.7 mmHg) and the Goldmann
      tonometer (18.1 +/- 4.7 mmHg) was statistically significant (p < 0.0001). Linear
      regression analysis revealed a good Ocuton S/Goldmann correspondence (r = 0.88, p
      = 0.0001). However, IOP values detected with the Ocuton were consistently
      overestimated, compared to those detected with the Goldmann tonometer. The
      correlation between corneal thickness and IOP was statistically significant both
      for the Goldmann (r = 0.510, p = 0.021) and for the Ocuton S tonometer (r =
      0.520, p = 0.019). No correlation was found between keratometry and IOP. The mean
      measurement obtained by self-tonometry (21.9 +/- 3.6 mmHg) showed no
      statistically significant difference when compared to the mean measurement
      obtained by an expert operator (21.3 +/- 3.4 mmHg). CONCLUSION: The Ocuton S
      tonometer is a safe instrument that can be used easily by the patient. However,
      in comparison to the Goldmann tonometer, it overestimates IOP and requires
      further technical and methodological refinements in order to ensure greater
      reliability.

PMID- 11952484
TI  - Outcome of vitrectomy in patients with Terson syndrome.
AB  - PURPOSE: To report findings and evaluate the results of vitrectomy in 22 eyes
      with Terson syndrome. METHODS: We reviewed retrospectively the records of
      patients who underwent pars plana vitrectomy as a result of vitreous haemorrhage.
      Twelve cases concerned unilateral vitrectomy and five concerned bilateral
      vitrectomy. The time interval between intracranial haemorrhage and vitrectomy was
      1-10 months (mean 5.9 months). RESULTS: During a mean follow-up of 23.3 months
      (range 1-69 months) visual acuity (VA) improved in 21 of 22 eyes. Preoperative VA
      was < or = 0.1 in 20 of 22 eyes, while postoperative VA was > or = 0.5 in 16 of
      21 eyes. Poor visual outcomes were mainly caused by retinal detachments (seven
      eyes, in which three were caused by proliferative vitreoretinopathy), epiretinal
      membranes (seven eyes) and optic atrophy (one eye). Our study concurs with recent
      reports suggesting early vitrectomy in bilateral cases and in cases where
      ultrasonography shows epiretinal membrane or proliferative retinopathy formation.

PMID- 11952485
TI  - Dorzolamide and ocular blood flow in previously untreated glaucoma patients: a
      controlled double-masked study.
AB  - PURPOSE: The aim of this study was to investigate the haemodynamic effects of
      topical dorzolamide treatment in eyes with newly detected and previously
      untreated glaucoma. METHODS: Forty-seven patients with open angle glaucoma were
      consecutively randomized to dorzolamide versus placebo TID during a 6-week double
      masked treatment trial. Ocular blood flow was investigated at baseline and on
      therapy using colour Doppler imaging of the retrobulbar vessels and scanning
      laser ophthalmoscope fluorescein angiograms of the retinal circulation. RESULTS:
      None of the flow parameters, retrobulbar or retinal, changed significantly on
      therapy when the results were analysed with the Bonferroni method. Analysis with
      non-simultaneous tests also failed to reveal any significant changes either in
      retrobulbar flow velocities in the central retinal artery, ophthalmic artery or
      in the short posterior ciliary arteries, or in the retinal parameters (arm-retina
      time, arteriovenous passage time, mean dye velocity or macular capillary
      velocity), while capillary velocities at the optic disc decreased significantly
      in the dorzolamide group (P = 0.03). Intraocular pressure reduction was
      significantly more pronounced in the dorzolamide group (P = 0.002), with - 4.8 +/
      2.9 mmHg (P < 0.0001) versus -1.8 +/- 3.0 mmHg in the placebo group (P = 0.006).
      CONCLUSIONS: The present study indicated no measurable vascular effects from
      topical dorzolamide treatment in previously untreated glaucoma eyes.

PMID- 11952486
TI  - Treatment of acute neonatal bacterial conjunctivitis: a comparison of fucidic
      acid to chloramphenicol eye drops.
AB  - PURPOSE: To compare the clinical and bacteriological effects of fucidic acid
      (Fucithalmic: 1.0%) and chloramphenicol (Minims(R): 0.5%) eye drops in neonates
      with a clinical diagnosis of acute conjunctivitis of suspected bacterial origin.
      METHODS: A TOTAL OF 456 N: ewborns with gestational age > 32 weeks with acute
      conjunctivitis of suspected bacterial origin acquired within the first 28 days of
      life were included in the study. They were randomly assigned to a 7-day treatment
      with eye drops using either fucidic acid (1.0%) (Fucithalmic) applied twice per
      day, or chloramphenicol (0.5%) (Minims Chloramphenicol) applied six times per
      day. The subjects were followed up with two visits (on days 1 and 8) and by
      telephone 2 weeks after the end of treatment. RESULTS: Eighty-nine per cent of
      the neonates treated with Fucithalmic were cured, compared to 87.9% of those
      treated with Minims Chloramphenicol (n.s). The drug was used as instructed in
      90.7% of patients treated with Fucithalmic and in 78.0% of those treated with
      Minims Chloramphenicol (P < 0.001). CONCLUSION: Treating neonatal conjunctivitis
      with fucidic acid is easier than with chloramphenicol and is equally effective.

PMID- 11952487
TI  - Refractive change during hyperbaric oxygen therapy. A clinical trial including
      ultrasound oculometry.
AB  - PURPOSE: To record changes in refraction and refractive parameters associated
      with a standard hyperbaric oxygen treatment protocol consisting of a 95 min
      session at > 95% oxygen at 2.5 atmospheres (ATA) given daily Monday to Friday, to
      a total of 30 sessions. PATIENTS AND METHODS: Seventeen of the 26 patients
      included were able to attend for ophthalmic assessment at time zero (to) and
      after 20 treatments (t20). Thirteen patients also had a post-treatment follow-up.
      Most patients were being treated for osteoradionecrosis after radiotherapy of ENT
      cancers, and drop-outs for the eye exam were common. Refraction was determined
      subjectively and by refractometry, before and after tropicamide 1% eyedrops.
      Refractive parameters were assessed by keratometry and by A-scan axial ultrasound
      measurement. RESULTS: Results are given for the 17 patients with to and t20
      assessments. The induced refractive change ranged from 0 to 1.5 D. When observed,
      refractive changes were myopic in nature. The shift averaged 0.58 D according to
      the refractometer and 0.49 D as subjectively assessed, with corresponding median
      change values being 0.62 and 0.39 D. The differences between 0 D and these
      values, although small, were statistically highly significant. CONCLUSIONS: The
      refractive changes associated with hyperbaric oxygen therapy were smaller than
      the literature had led us to expect. No significant change in axial eye length
      measurements was found, and keratometry readings reflected only minimal change,
      although this was statistically significant on a 0.05 level. Therefore it is most
      likely that lens changes, whether in internal refractive indices or curvatures,
      accounted for the transitory shift towards more myopic/less hyperopic values.

PMID- 11952488
TI  - Biochemical markers of the L-arginine-nitric oxide pathway in the aqueous humour
      in glaucoma patients.
AB  - PURPOSE: To study the role of the L-arginine-nitric oxide (NO) pathway in aqueous
      humour dynamics by measuring nitrate, nitrite and cyclic (cGMP) levels in
      guanosine 3',5'-monophosphate the aqueous humour of glaucomatous and
      nonglaucomatous cataract patients. METHODS: The study involved 38 glaucoma
      patients undergoing unilateral cataract surgery in the glaucomatous eye and 38
      cataract control patients matched for sex, age, smoking habits and organic
      nitrate medication. All subjects underwent ophthalmic examination, and blood
      pressure was measured preoperatively. Nitrite, nitrate and cGMP levels were
      measured in aqueous humour and serum. RESULTS: The NOx (nitrite + nitrate),
      nitrite and cGMP concentrations in the aqueous humour were slightly higher in the
      glaucoma patients than in the control patients, but the differences did not reach
      statistical significance. The levels of cGMP in serum were higher in the glaucoma
      patients (P = 0.053). The subgroup of glaucoma patients with pseudoexfoliation
      had lower NOx and nitrite values in the aqueous humour (P = 0.046 and P = 0.345,
      respectively) than the matched controls, while cGMP levels were higher (P =
      0.043). Levels of NOx and nitrite in the aqueous humour were higher in patients
      using oral nitroglycerin (P = 0.062 and P = 0.042, respectively) than in patients
      without this medication. Blood pressure was higher in the glaucoma patients, with
      a mean of 165/89 mmHg as compared to 153/81 mmHg in the controls (P-values
      0.071/0.008). CONCLUSIONS: No differences in NO metabolites were found between
      glaucoma and control patients. However, any real changes may have been disguised
      by optimal medication of glaucoma. Low NOx and high cGMP levels in the aqueous
      humour of pseudoexfoliation patients warrant further evaluation in a larger
      study.

PMID- 11952489
TI  - Usher syndrome clinical types I and II: could ocular symptoms and signs
      differentiate between the two types?
AB  - PURPOSE: Usher syndrome types I and II are clinical syndromes with substantial
      genetic and clinical heterogeneity. We undertook the current study in order to
      identify ocular symptoms and signs that could differentiate between the two
      types. METHODS: Sixty-seven patients with Usher syndrome were evaluated. Based on
      audiologic and vestibular findings, patients were classified as either Usher type
      I or II. The severity of the ocular signs and symptoms present in each type were
      compared. RESULTS: Visual acuity, visual field area, electroretinographic
      amplitude, incidence of cataract and macular lesions were not significantly
      different between Usher types I and II. However, the ages when night blindness
      was perceived and retinitis pigmentosa was diagnosed differed significantly
      between the two types. CONCLUSIONS: There seems to be some overlap between types
      I and II of Usher syndrome in regard to the ophthalmologic findings. However,
      night blindness appears earlier in Usher type I (although the difference in age
      of appearance appears to be less dramatic than previously assumed). Molecular
      elucidation of Usher syndrome may serve as a key to understanding these
      differences and, perhaps, provide a better tool for use in clinical diagnosis,
      prognosis and genetic counseling.

PMID- 11952490
TI  - Uveal effusion and ultrasonic imaging: a clinical series.
AB  - PURPOSE: To establish the diagnostic role of imaging by ultrasound for the
      diagnosis of uveal effusion syndrome. METHODS: Using ultrasonic imaging features
      as the main criteria for evaluation, the recorded data from 16 patients with
      presumed uveal effusion seen between 1994 and 2000 were reviewed and analysed for
      clinical manifestations and current diagnostic suggestions. Eventually, as
      cumulating experience suggested that ultrasound is capable of indicating uveal
      effusion, the study set-up became in part more prospective. RESULTS: The two main
      ultrasonic features found were: (1) extended multi-layered detachment patterns by
      B-scan, often kinetically mobile; (2) a spongy oedematous ciliary body region,
      often with interstitial lacunae, as demonstrated by high-resolution ultrasound
      biomicroscopy (50 Mhz). CONCLUSIONS: In patients with visual loss and ambiguous
      detachment-like fundus pathology, ultrasonic features are often of practical
      guidance for diagnosing uveal effusion syndrome.

PMID- 11952491
TI  - Cataract in children after bone marrow transplantation: relation to conditioning
      regimen.
AB  - PURPOSE: To compare the frequency of cataract development in bone marrow
      transplanted children who have been given either total body irradiation (TBI) or
      busulphan as conditioning treatment before bone marrow transplantation (BMT).
      MATERIAL AND METHODS: Forty-five children who underwent BMT between 1987 and 1994
      were included in the study. Twenty-one children were conditioned with TBI and 24
      with busulphan before BMT. All children underwent an ophthalmic examination
      before BMT in order to exclude lens opacities. Yearly examinations for 2-10 years
      were performed after BMT. RESULTS: Cataracts developed in 20 of the 21 (95%)
      children conditioned with TBI and in five of the 24 (21%) children conditioned
      with busulphan. There was no relationship between cataract development and age at
      BMT, or between cataract development and prednisolone given before or after BMT.
      CONCLUSION: The present study confirms earlier reports of the high risk of
      cataract development after TBI and suggests that busulphan is related to cataract
      development, although less frequently than TBI. The report discusses the possible
      additive effect of the disease itself, of any corticosteroid treatment and of
      other cytostatic drugs. It then stresses the importance of early diagnosis of
      cataracts in children in order to prevent the development of amblyopia.

PMID- 11952492
TI  - Optical coherence tomography in choroidal neovascular membrane associated with
      Best's vitelliform dystrophy.
AB  - A 29-year-old black male with Best's dystrophy presented an elevated choroidal
      neovascular membrane in the right eye that was diagnosed and followed with
      fluorescein-indocyanine green angiography and optical coherence tomography. The
      subretinal neovascularization was successfully treated with argon laser
      photocoagulation. One month later, the visual acuity improved and an optical
      coherence tomography confirmed regression of the serous macular detachment. The
      final clinical picture remained stable for 12 months of follow-up.

PMID- 11952493
TI  - ON-pathway disturbance in two siblings.
AB  - PURPOSE: To present two clinical cases diagnosed with predominant cone dystrophy
      and demonstrating early disturbance in the on-centre bipolar cells (ON-pathway).
      METHODS: Electrophysiological findings are presented in two siblings with
      predominant cone dystrophy. The subjects showed no remarkable ophthalmoscopic or
      fluorescein angiographic retinal changes, but demonstrated progressive visual
      disturbance during their 20s. RESULTS: The electroretinograms (ERGs) showed
      reduced dark-adapted responses but the positive component of the photopic ERG was
      absent. Response to 30 Hz flicker was severely reduced. Electroretinograms
      elicited by long-duration stimuli showed a loss of the b-wave, and the off
      response was slightly reduced. In both patients, multifocal ERGs (m-ERGs) were
      more reduced within the central 10 degrees, where the ON-pathway is normally a
      major contributor. CONCLUSION: We conclude that these patients may be affected by
      an abnormality of the synapses of the cone receptors and that their decrease in
      vision might, at least initially, be due to selective ON-pathway dysfunction.

PMID- 11952498
TI  - Myopia and glaucoma.

PMID- 11952501
TI  - Ensuring patient safety: what lessons can be learned from device-related adverse
      events in hemodialysis?

PMID- 11952502
TI  - Improving the clinical patency of prosthetic vascular and coronary bypass grafts:
      the role of seeding and tissue engineering.
AB  - In patients requiring coronary or peripheral vascular bypass procedures,
      autogenous vein is currently the conduit of choice. If this is unavailable, then
      a prosthetic material is used. Prosthetic graft is liable to fail due to
      occlusion of the graft. To prevent graft occlusion, seeding of the graft lumen
      with endothelial cells is undertaken. Recent advances have also looked at
      developing a completely artificial biological graft engineered from the patient's
      cells with properties similar to autogenous vessels. This review encompasses the
      developments in the two principal technologies used in developing hybrid coronary
      and peripheral vascular bypass grafts, that is, seeding and tissue engineering.

PMID- 11952503
TI  - Ionic dialysance measurement is urea distribution volume dependent: a new
      approach to better results.
AB  - Conductivity (CD)-based dialysance measurements precisely match urea dialysance
      with <5% difference. For measurement, a CD step-profile is applied by increasing
      dialysate inlet CD at time t0 for 10% above baseline and lasting for 2-5 min
      until t1, followed by a decrease to -4% until t2 and a final return to baseline,
      meanwhile recording dialysate CD at filter inlet (cdi) and outlet (cdo),
      dialysate flow (Qd), and ultrafiltration (UF)-rate (Qf). Electrolytic dialysance
      (KeCn) is calculated by KeCnI,J = (1 -[cdoI-cdoJ]/[cdiI-cdiJ])(Qd+Qf) with time
      index I not = J. The combinations in I,J are not equivalent: KeCn0,1 < KeCn1,2 <
      KeCn0,2. Each difference is 2% to 5%, and a difference versus urea clearance
      remains. An in vivo on-line clearance study (10 patients, 100 dialysis sessions,
      265 measurements) with automatic electrolytical dialysance measurements and
      permanent data recording was conducted. Two methods were applied: a CD step
      profile and a significantly smaller, dynamic CD bolus. Both were compared to
      laboratory reference of urea clearance. Reference Kt/V has been calculated using
      equilibrated single-pool methods and direct quantification. Urea generation was
      ignored. The results are as follows. The reference blood-side urea clearance was
      164.0 +/- 11.8 ml/min, n = 265. The mean errors of the ionic dialysance results
      are KeCn0,1: -9.1 +/- 4.8%, n = 250; KeCn1,2: -5.6 +/- 4.4%, n = 250; KeCn0,2:
      6.8 +/- 7.7%, n = 250; KeCnBolus: 0.1 +/- 4.8%, n = 162. The KeCnI,J error is
      urea distribution volume related. Kt/V comparison to equilibrated single pool is
      as follows: KeCn1,2t/V: 0.0 +/- 5.0% (r = 0.96, n = 45); KeCnBolust/V: 5.3 +/-
      3.9% (r = 0.98, n = 44). The comparison to direct quantification is as follows:
      KeCn1,2t/V: -2 +/- 6.4% (r = 0.95, n = 68); KeCnBolust/V: 3.2 +/- 6.3% (r = 0.95,
      n = 66). V could roughly be measured. Dialysance measured by the step-function
      method was dependent on sodium load and distribution volume while the CD-bolus
      dialysance was not. Errors are generated by measurement-induced sodium shift that
      is sufficient even to estimate urea distribution volume. For dialysance
      measurements, small dynamic CD boli are preferable to stable step functions.

PMID- 11952504
TI  - Effect of growth factors on ex vivo bone marrow cell expansion using three
      dimensional matrix support.
AB  - To develop a culture system for bone marrow (BM) cell expansion, we examined the
      effect of growth factors (GFs) on the proliferation and differentiation of BM
      cells cultured in three-dimensional (3D) scaffolds of porous polyvinyl formal
      (PVF) resin. Murine BM cells were cultured for 2 weeks in the PVF resin or in
      culture dishes as a control, in the presence or absence of 4 GFs (erythropoietin,
      stem cell factor, interleukin [IL]-3, and IL-6). These GFs remarkably stimulated
      cell proliferation both in PVF and dish cultures. In addition, the PVF cultures
      showed enhanced cell proliferation in comparison with the corresponding dish
      cultures. Moreover, PVF cultures with GFs revealed the highest number of colony
      forming units and the highest percentage of hematopoietic progenitor cells (HPCs)
      among all the cultures examined. Therefore, this 3D PVF culture system with GFs
      is considered as a potential alternative method for the ex vivo expansion of
      HPCs.

PMID- 11952505
TI  - Modulation of hepatocyte function in an immortalized human hepatocyte cell line
      following exposure to liver-failure plasma.
AB  - For hepatocytes to function effectively in a bioartificial liver device,
      maintained function in the milieu of plasma from patients with liver failure will
      be required. We have investigated the effect of plasma obtained at plasmapheresis
      from patients with acute liver failure on the performance of the human hepatocyte
      cell line HHY41 in liver-failure plasma, normal plasma, and culture medium.
      Cytotoxicity of plasma, DNA synthesis by thymidine incorporation, oxidative
      status, and cytochrome P450 functions were assayed after a 16 h culture with
      normal plasma, liver-failure plasma, or culture medium. Some, but not all,
      samples of liver-failure plasma were deleterious to the performance of the cell
      line, inducing cytotoxicity and oxidative stress, with diminished DNA synthesis,
      protein synthesis, and cytochrome P4501A activity. Strategies to minimize the
      toxic effects of liver-failure plasma may improve the performance of liver cells
      in extracorporeal liver-support devices.

PMID- 11952506
TI  - Interaction of the cardiovascular system with an implanted rotary assist device:
      simulation study with a refined computer model.
AB  - In recent years, implanted rotary pumps have achieved the level of extended
      clinical application including complete mobilization and physical exercise of the
      recipients. A computer model was developed to study the interaction between a
      continuous-flow pump and the recovering cardiovascular system, the effects of
      changing pre- and afterloads, and the possibilities for indirect estimation of
      hemodynamic parameters and pump control. A numerical model of the cardiovascular
      system using Matlab Simulink simulation software was established. Data of
      circulatory system modules were derived from patients, our own in vitro and in
      vivo experiments, and the literature. Special care was taken to simulate properly
      the dynamic pressure-volume characteristics of both left and right ventricle, the
      Frank-Starling behavior, and the impedance of the proximal vessels. Excellent
      correlation with measured data was achieved including pressure and flow patterns
      within the time domain, response to varying loads, and effects of previously
      observed pressure-flow hysteresis in rotary pumps. Potential energy, external
      work, pressure-volume area, and other derived heart work parameters could be
      calculated. The model offers the possibility to perform parameter variations to
      study the effects of changing patient condition and therapy and to display them
      with three-dimensional graphics (demonstrated with the effects on right
      ventricular work and efficiency). The presented model gives an improved
      understanding of the interaction between the pump and both ventricles. It can be
      used for the investigation of various clinical and control questions in normal
      and pathological conditions of the left ventricular assist device recipient.

PMID- 11952507
TI  - Chronic heart failure model in rabbits based on the concept of the
      bifurcation/trifurcation coronary artery branching pattern.
AB  - The aim of this study was to develop a reliable chronic heart failure model by
      coronary artery ligation in the rabbit on the basis of the new concept of the
      bifurcation/trifurcation classification system of the epicardial branching
      pattern of the left coronary artery (LCA). New Zealand White rabbits (n = 37)
      were divided into 3 experimental groups: a posterolateral division of the
      bifurcation pattern of the LCA was ligated at the 75% level from the apex along
      the course of the division (B75 group, n = 15); a lateral division of the
      trifurcation pattern at the 75% level (T75 group, n = 11); and a posterolateral
      division of the bifurcation pattern at the 50% level (B50 group, n = 11). The
      infarct size and the lung and liver water content were determined at 4 weeks
      following ligation. The Q or QS wave on electrocardiogram (ECG) and the left
      ventricular (LV) dimensions (LVIDs and LVIDd), fractional shortening (FS), and
      mitral E-point to septal separation on ultrasonography were assessed at 10 min
      and at preligation and at 1, 2, and 4 weeks following ligation. The B75 group
      showed higher mortality (46.7%) than the T75 and B50 groups. The mean infarct
      size in the B75 group was 22.55 +/- 5.34% which was significantly larger than in
      the B50 (13.84 +/- 5.46%) and T75 (12.90 +/- 2.67%) groups (p < 0.001). All 3
      groups had significantly greater Q or QS wave amplitudes on ECG at 1, 2, and 4
      weeks than at 10 min after ligation. At 1 and 2 weeks after ligation, LVIDd,
      LVIDs, and FS showed significant dfferences in the B75 group as compared with the
      other groups. The level of ligation of the LCA for the development of a reliable
      chronic heart failure model in the rabbit is recommended to be 50% from the apex
      along the course of the posterolateral division in the bifurcation pattern and
      75% from the apex along the course of the lateral division in the trifurcation
      pattern.

PMID- 11952508
TI  - Intravenous ascorbic acid administration for erythropoietin-hyporesponsive anemia
      in iron loaded hemodialysis patients.
AB  - Intravenous ascorbic acid administration (IVAA) could override recombinant human
      erythropoietin (rHuEPO) resistance in hemodialysis patients with iron overload.
      We investigated the hematopoietic response to IVAA in iron-overloaded
      hemodialysis patients. We included 36 patients whose ferritin levels were higher
      than 500 microg/L and who needed more than 100 U/kg/week of rHuEPO. The study
      included an initial phase (500 mg IVAA twice weekly was administered to all of
      the patients for 8 weeks) and a maintenance phase (patient groups were formed;
      Group 1 received IVAA 500 mg/week for 8 weeks and Group 2 received no therapy).
      We observed a significant increase in hematocrit and transferrin saturation and a
      decrease in the percentage of hypochromic red cells and ferritin levels at the
      end of the initial phase. The total weekly-required rHuEpo dose and
      rHuEpo/hemoglobin also fell significantly after the initial phase. The response
      remained stable in patient groups during the maintenance phase. In 6
      nonresponders, the hypochromic red cells were <10%. In conclusion, IVAA
      effectively overrides rHuEPO resistance in iron-overloaded hemodialysis patients.

PMID- 11952509
TI  - Comparison of two filter combinations for low-density lipoprotein apheresis by
      membrane differential filtration: a prospective crossover controlled clinical
      study.
AB  - Membrane differential filtration is an accepted procedure for the extracorporeal
      removal of low-density lipoprotein (LDL). Reduction rates largely depend on the
      nature of the membranes and are ideally evaluated in a crossover study design.
      Four patients who had been treated by LDL apheresis for at least 6 months were
      included. Six consecutive weekly sessions (40 ml plasma/kg body weight) were
      scheduled per system (Plasmacure PS06/Evaflux Eval 5A [Kuraray] versus Plasmaflo
      OP05W/Cascadeflo AC1770 [Asahi]). Laboratory measurements indicated reductions of
      plasma concentrations for fibrinogen (37% [Kuraray] versus 44% [Asahi]), IgG (15%
      versus 20%), IgA (24% versus 28%), IgM (63% versus 53%), and total protein (11%
      versus 16%). Total cholesterol was eliminated by 52% versus 49%, LDL by 67%
      versus 66%, triglycerides by 56% versus 41%, and high-density lipoprotein by 10%
      versus 20%. Three therapies employing the Asahi filter combination were
      terminated prematurely due to saturation of the plasma fractionator. In
      conclusion, despite similar physical properties, the membranes differ
      significantly concerning selectivity and sensitivity to saturation.

PMID- 11952510
TI  - Effect of filtration leukocytapheresis therapy: modulation of white blood cell
      enzyme activities in patients with rheumatoid arthritis.
AB  - We treated 12 patients with rheumatoid arthritis by filtration leukocytapheresis
      (FLCP) and evaluated its effect on leukocyte enzyme activities. We calculated the
      number of leukocytes removed and assessed the clinical response. We also
      evaluated the cellular enzyme activities of elastase and dipeptidylpeptidase IV
      (DPP IV). Out of 12 patients, 7 patients achieved 20% improvement for 4 weeks
      following FLCP. The FLCP treatment resulted in removal of 96% of granulocytes,
      98% of monocytes, and 61% of lymphocytes. Granulocytes and monocytes with high
      elastase activity were effectively removed by FLCP. The elastase activity of
      granulocytes was increased 4 weeks after the last FLCP only in responders. On the
      other hand, the DPP IV activity of lymphocytes was low at 4 weeks after the last
      FLCP in responders. Modulation of leukocyte enzyme activities is one of the main
      effects of FLCP therapy and alteration of granulocytes, monocytes, and
      lymphocytes.

PMID- 11952511
TI  - Relationship between interdialytic weight gain and acid-base status in
      hemodialysis by bicarbonate.
AB  - The aim of this study was to determine the relationship between interdialytic
      weight gain and acid-base balance pre- and posthemodialysis in uremic patients
      undergoing hemodialysis with a high bicarbonate dialysate (39 mmol/L). To this
      end we studied 8 stable uremic patients on regular hemodialysis thrice weekly who
      had stable hematocrit values for at least 3 months, similar clinical
      characteristics including dry weight but widely varying interdialytic weight
      gain. Arterial line blood samples were collected anaerobically in heparinized
      syringes pre- and posthemodialysis in 4 consecutive hemodialysis sessions for the
      determination of pH, Paco2, and HCO3. Prehemodialysis values (mean +/- SD) were
      pH = 7.34 +/- 0.03, Paco2 = 36.43 +/- 1.4, and Hco3 = 20.1 +/- 1.55.
      Posthemodialysis values were pH= 7.47 +/- 0.02, Paco2 = 38.72 +/- 2.0, and HCO3 =
      27.73 +/- 1.72. In other words, patients were moderately acidemic prior to and
      moderately alkalemic after the hemodialysis session. Of note, a significant
      negative correlation was revealed between the interdialytic weight gain and the
      values of prehemodialysis blood pH (r = -0.721, p < 0.001) and HCO3 (r = -0.836,
      p < 0.001) and posthemodialysis pH (r = -0.533, p < 0.001), Paco2 (r = -0.623, p
      < 0.001) and HCO3 (r = -0.815, p < 0.001), suggesting an important role of the
      interdialytic weight gain on acid-base equilibrium of uremic patients undergoing
      hemodialysis. Thus, patients with high interdialytic weight gains may require
      higher bicarbonate concentrations to achieve normal acid-base status whereas
      patients with low interdialyic weight gains may require lower bicarbonate
      concentrations to prevent alkalemia at the end of dialysis.

PMID- 11952512
TI  - Bedside testing with the new CoaguChek Pro activated clotting time assay in
      dialysis.
AB  - The objective of this study was to assess the analytical performance of CoaguChek
      Pro activated clotting time (ACT) assay using 2 lots versus Hemochron Celite and
      glass ACT regarding ACT values and correlations versus heparin levels.
      Determinations were performed using 4 CoaguChek Pro meters and 1 Hemochron 801
      meter. Samples were collected during hemodialysis before, after start of
      heparinization, and 2 h later. Agreement between CoaguChek Pro ACT and Hemochron
      Celite was good (r = 0.82, slope = 1.12) and moderate with Hemochron glass (r =
      0.83, slope = 0.97). Agreement between both CoaguChek Pro lots was r = 0.98.
      Agreement between the activators, Hemochron Celite, and glass was r = 0.73.
      Correlation between CoaguChek Pro ACT and heparin concentration was r = 0.88 and
      0.94; for Hemochron the correlation was r = 0.75 (Celite) and r = 0.73 (glass).
      CoaguChek Pro ACT is therefore suitable for monitoring heparin administration
      during dialysis.

PMID- 11952513
TI  - Flow dynamic comparison of peripheral venous cannulas used with centrifugal pump
      assistance in vitro.
AB  - Because of the risk of vein collapse, the benefits of using a centrifugal pump to
      assist venous drainage for cardiopulmonary bypass are limited when the tips of
      peripheral cannulas are maintained within the vena cava. Using a mock circuit
      including 20 mm diameter latex tubing to mimic a vena cava, we compared the
      performance of 6 commercially available peripheral venous cannulas and attempted
      to determine potential factors influencing maximal flow drainage before vein
      collapse. A close correlation was observed with the total hole area of the
      cannula. Best performance (5.10 +/- 0.08 L/min) was obtained with an 8 mm
      internal diameter (ID) cannula and 343 mm2 total hole area. A larger cannula (ID
      9.2 mm) with only 209 mm2 total hole area drained 5.03 +/- 0.05 L/min whereas a
      smaller cannula (ID 6.7 mm) with a total hole area of 586 mm2 also allowed a
      similar flow of 5.03 +/- 0.12 L/min. Therefore, the total hole area appears to be
      a critical factor in designing peripheral cannulas used in restricted chambers
      such as vena cavae.

PMID- 11952514
TI  - Investigation of the flow performance of a nutating blood pump by computational
      fluid dynamics.
AB  - In centrifugal blood pumps, blood is moved into a circular path with the help of
      an impeller. In a nutating pump, the nutating body takes over the role of the
      impeller. Since the nutating body itself does not rotate, this pump needs no
      seal, no blood contacting, and no magnetic bearings. To examine the suitability
      of the nutating pump principle for mechanical heart assist, the flow performance
      of different nutating pump models was investigated by computational fluid
      dynamics. The geometrical parameters of the pump were varied and flow-pressure
      curves were calculated for 12 models at different rotation frequencies. All
      models showed satisfactory flow-pressure curves. One model was computed minutely
      at 1 flow configuration to examine shear stresses within the fluid. A flow of 5
      L/min and a frequency of 3,300 rotations per min (rpm) resulted in a differential
      pressure of 85 mm Hg. The maximum shear stress in the fluid at this flow was
      estimated to be 193 Pa which is considered to be an acceptable value for a blood
      pump.

PMID- 11952516
TI  - Whither rural health? Reviewing a decade of progress in rural health.
AB  - The problems associated with rural and remote health have been widely recognised
      by health workers, rural communities and health professions for some time. Yet it
      has only been in the past decade that any concerted effort has been made to
      address rural health issues. Today the state of health in rural Australia remains
      less than optimal. The tenth anniversary of the Australian Journal of Rural
      Health provides the opportunity to reflect on what progress has been achieved
      over the past decade, to recognise those factors that have contributed most to
      the implementation of policies designed to address the health needs of rural and
      remote Australians, and to discuss outstanding impediments and barriers to
      resolving rural health issues.

PMID- 11952517
TI  - Developing a cardiac rehabilitation education resource for rural health workers
      in Queensland: reviewing the process and outcomes.
AB  - The provision of cardiac rehabilitation services to people living in rural and
      remote areas is often limited to the nearest large hospital situated in urban
      coastal centres, leaving a gap in the rehabilitation of cardiac patients. This
      paper discusses the development, composition and the results of a process
      evaluation of a cardiac rehabilitation education resource for rural health
      workers. The development of the structure and content of the manual were informed
      by a review of current rehabilitation literature, the results of focus groups
      with 60 rural health workers in five Queensland rural centres, and survey results
      of 135 rural cardiac patients admitted to five Queensland hospitals. The draft
      manual was trialled by health workers in seven rural centres throughout
      Queensland by the National Heart Foundation (Queensland Division). The results of
      the process evaluation provided valuable feedback on the efficacy of the manual
      as an educational resource for rural health workers in the cardiac rehabilitation
      of their patients. Specific content in the educational resource was strengthened
      as a result of this evaluation. The limitations of the evaluation and suggestions
      for its improvement are also discussed. The paper highlights the importance of
      this level of evaluation in the development of health promotion education
      resources.

PMID- 11952518
TI  - Primary mental health-care model in rural Tasmania: outcomes for patients.
AB  - Community and doctor concern over the disproportionately high suicide rate in a
      rural area of Tasmania resulted in a project employing a mental health worker to
      provide counselling, educate patients and the public about mental illness,
      improve the skills of local health workers, liaise with other counselling
      agencies and undertake research into mental health in the area. Figures on mental
      health problems in the area and the positive effects of the project on access to
      treatment and improvement in symptoms and functioning are presented. The results
      from this inexpensive, shared care/attachment model point to its potential
      application in primary care in other areas of Australia.

PMID- 11952519
TI  - Helping hospitalised clients quit smoking: a study of rural nursing practice and
      barriers.
AB  - Brief interventions have been identified as a useful tool for facilitating
      smoking cessation, particularly in the acute care setting and in areas where
      access to specialist staff is limited, such as rural Australia. A self
      administered survey was used to determine current rural nursing staff practices
      in relation to brief intervention for smoking cessation, and to ascertain the
      perceived level of support, skills, needs and barriers amongst these staff to
      conducting brief interventions. The major findings include that while the
      majority of respondents were aware of their patients' smoking status, most were
      not very confident about assisting smoking patients to quit. Casually employed
      nurses were much less likely to be aware of patient smoking status than nurses
      employed full-time or permanent part-time. Only one-quarter to one-third of
      nurses did not believe assisting patients to quit was part of their role, and the
      vast majority of nurses reported that they were non-smokers. Future programs
      incorporating the routine use of brief interventions will need to consider these
      findings.

PMID- 11952520
TI  - Medication compliance problems in general practice: detection and intervention by
      pharmacists and doctors.
AB  - Medication compliance; the role of a portable Medical Summary Card as a
      compliance aid; and the role of a medical practice-based clinical pharmacist in
      identifying medication-related problems in a rural general practice setting is
      evaluated. A clinical pharmacist checked the medications of 50 predominantly aged
      patients against their medical summary and noted inconsistencies and potential
      medication problems. From this information the general practitioner (GP) assessed
      patient compliance with prescribed medications and transcribed the correct
      medication regimen and medical problems onto a Medical Summary Card for the
      patient to carry. Forty per cent of the patients were non-compliant. A Medical
      Summary Card alone was unable to improve compliance. Issues noted by the clinical
      pharmacist warranted a change in therapy for 8% of patients. Eighteen per cent of
      patients provided medical information to the clinical pharmacist of which the GP
      was unaware. Non-compliance with prescribed medications is common. A portable
      Medical Summary Card may not rectify this problem. Patients' withholding medical
      information from their medical practitioner is of particular concern.

PMID- 11952521
TI  - Capacity building in rural mental health in Western Australia.
AB  - A regional success story in capacity building in terms of workforce development
      in rural Western Australia is described. A rural and remote distance education
      program in mental health was delivered in 1999 across 10 rural sites to 31 health
      professionals (26 general nurses, four allied health and one Aboriginal health
      worker) who are in contact with mentally ill patients at the primary level in
      country areas. Evaluation on completion of the program and at 4 months
      postprogram was extremely positive, with participants reporting that they have
      gained knowledge of mental health management regimens, developed mental health
      assessment skills and enhanced their clinical practice. Both participants and
      their line managers identified that the program had greatest impact on improving
      relationships with the mental health team. The program has also been an example
      of capacity building in terms of innovative resourcing to address a statewide
      need in mental health education for those at the forefront of rural practice.

PMID- 11952522
TI  - Rural urgent care models: what are they made of?
AB  - The study aimed to identify the elements that constitute rural urgent care
      systems. Participation in the study was sought from health professionals, welfare
      and emergency services sectors, and community members. Primary data were
      collected from informants through interviews and focus groups in five rural
      communities of different sizes. Twelve common elements to rural urgent care
      systems were identified and divided into two categories: (i) infrastructure; and
      (ii) personnel. Infrastructure included organisational support, community
      support, transport, communication and coordination processes, facilities and
      equipment, and community knowledge and information. Personnel included nurses,
      doctors, community leaders, health and welfare professionals, emergency service
      workers and ambulance officers. The study's major outcome was the recognition
      that rural urgent care systems consist of a balance of interrelated elements.
      These elements are context driven, with geographical, social and economic
      environments having a substantial impact on the ability of rural communities to
      develop and sustain their urgent care systems.

PMID- 11952523
TI  - Amalgamation of health services in south-west Victoria: reinvention or survival?
AB  - In Australia "the hospital" has long been considered the cornerstone of small,
      rural health services. However, this premise has been altered significantly by
      the introduction of casemix loading and diagnostic-related groups that promote a
      rationalised output-based model of management. In the light of these changes,
      many rural health services have struggled to reinvent themselves by establishing
      a range of service models such as Multi-purpose Service (MPS) and Health Streams,
      while maintaining traditional models (i.e. bush nursing centres, nursing homes
      and aged-care facilities). These changes are about survival. This paper analyses
      one such case in south-west Victoria, the Macarthur and District Community
      Outreach Service, and compares the outcomes with other similar Victorian rural
      health research projects. Particular attention is paid to the nature of the
      health services, the management of change and the proposed health outcomes for
      the local rural communities. In conclusion, it is argued that this study adds to
      the body of knowledge surrounding the construction of models of community health
      and development programming, These models impact upon future rural and remote
      area initiatives throughout Australia.

PMID- 11952524
TI  - Faecal occult blood test: current practice in a rural Queensland community.
AB  - The findings of a recent telephone survey of 604 residents (50-74 years of age)
      in a rural community in Queensland are presented. The survey focused on the
      participants' knowledge concerning the faecal occult blood test (FOBT) and their
      previous testing history. Responses were analysed in terms of gender, age and
      education differences. More than half of all participants were aware of the FOBT,
      and 109 (18%) had undergone FOBT in the past. Fewer understood the importance of
      "health checks without symptoms" than the "advantage of early treatment". The
      most common reasons to use FOBT were: "prevention" and "I want to know if I have
      cancer". A person's gender, age and education were shown to be associated with
      their knowledge and beliefs. These results suggest an increase in the use of the
      FOBT with time (in relation to previous surveys), but a poor understanding of its
      place in promoting health.

PMID- 11952530
TI  - Abstracts of the European Society for Paediatric Urology 13th Annual Meeting,
      April 2002.

PMID- 11952525
TI  - Using videoconferencing to deliver a health education program to women health
      consumers in rural and remote Queensland: an early attempt and future plans.
AB  - Women's Health Queensland Wide, a non-government education and information
      organisation funded by Queensland Health, used videoconferencing to present a
      public education seminar on menopausal health to women health consumers across
      south-west Queensland. A panel of speakers addressed a live audience in a
      provincial city, with a further 10 sites participating remotely via
      videoconferencing, each with a local health worker supporting the seminar. Both
      local and remote audience members were given opportunities to ask questions of
      the speakers. Audience members were asked to complete feedback forms and their
      responses are presented. Overall, audience members were very positive about both
      the content of the event and its method of delivery. They also provided comments
      relating to the structure of the program, the difficulties of running a live and
      distant seminar and the needs of remote audiences. Based on this information,
      Women's Health Queensland Wide has adapted future videoconference seminars to
      better meet the needs of rural and remote women.

PMID- 11952532
TI  - Vitamin E for dapsone-induced headache.

PMID- 11952534
TI  - Topical preparations for the treatment of psoriasis: a systematic review.
AB  - BACKGROUND: There is clinical uncertainty about the appropriate use of first-line
      topical treatments for psoriasis. OBJECTIVES: To assess the relative
      effectiveness and tolerability of topical treatments for psoriasis suitable for
      use both in primary and secondary care. METHODS: All major medical databases of
      published literature were searched electronically; references of trial reports
      and recent reviews were searched; authors and companies were contacted for
      missing data from published reports. The study selection comprised: (1)
      randomized placebo-controlled trials of topical treatments for psoriasis; and (2)
      randomized head-to-head studies of the new vitamin D3 derivative treatments for
      psoriasis that reported clinical outcome using a Total Severity Score (TSS),
      Psoriasis Area Severity Index or Investigator Assessment of Global Improvement.
      Eligibility and validity were assessed and data extracted independently by two
      authors. Clinical outcomes were pooled using a random effect standardized
      weighted mean difference (SWMD) metric, including 3380 patients randomized in 41
      placebo (vehicle)-controlled trials and 4898 patients randomized in 28 head-to
      head studies. RESULTS: There was a significant benefit in favour of active
      treatments against vehicle, SWMD: -1.06 (95% confidence interval [CI]: -1.26 to 
      0.86), approximately a 2-point improvement on a 12-point TSS after 6-8 weeks of
      treatment. The only significantly different benefit was for very potent
      corticosteroids: SWMD: -1.51 (95% CI: -1.76 to -1.25), approximately a 3-point
      improvement on a 12-point TSS. Head-to-head studies support these findings,
      except that calcipotriol was estimated to be more effective than dithranol, coal
      tar and other vitamin D3 derivatives. Polytherapy, using a potent steroid and
      calcipotriol, was more effective than calcipotriol alone: SWMD 0.42 (95% CI: 0.12
      0.72 ) approximately a 0.8-point improvement on a 12-point TSS. No important
      differences in withdrawal or reporting of adverse events were identified.
      CONCLUSIONS: Trials of short duration neither adequately inform the management of
      chronic disease nor describe the sequelae of treatment. The evidence base for
      long-term care, reflecting the disease pathway, should be improved. Combination
      therapy with topical vitamin D analogues and steroids, and maintenance therapy
      following treatment response merit further investigation.

PMID- 11952536
TI  - Technical prerequisites for in vivo microdialysis determination of interleukin-6
      in human dermis.
AB  - BACKGROUND: Cutaneous microdialysis in vivo in human skin is demonstrably of use
      in the study of skin metabolism, percutaneous absorption and skin inflammation. A
      promising area for cutaneous microdialysis is the measurement of cytokines. This
      requires catheters equipped with membranes permeable to molecules of high
      molecular weight. OBJECTIVES: To address technical problems of poor sample volume
      retrieval and analysis sensitivity in the simplest model of provocation, namely
      the insertion of the catheter itself in vivo into human dermis. METHODS: Use of a
      polyethylenesulphone membrane, with a cut-off value of 100,000 Da, allowed
      measurement of target molecules of large molecular weight. Using an adaptation of
      a commercially available high sensitivity enzyme-linked immunosorbent assay, the
      ubiquitous proinflammatory cytokine interleukin (IL)-6 was measured in the normal
      skin of six healthy volunteers after insertion of the microdialysis catheter.
      RESULTS: Reliable sample volumes and high analyte recovery were achieved either
      by push-pull pumping or by standard pumping using a perfusate consisting of
      Ringers Dextran 60 Braun. No IL-6 was detected in 25 of 26 samples taken during
      the first 100 min after catheter insertion. The IL-6 concentration then increased
      and remained elevated for the duration of the experiments. CONCLUSIONS: Technical
      and analytical modifications in the microdialysis technique have allowed the
      measurement of IL-6 in vivo in human dermis. It is suggested that the cytokine
      production is the result of the dermal trauma caused by catheter insertion, but
      the cellular source of the IL-6 is at present unknown.

PMID- 11952535
TI  - Slow release iodine preparation and wound healing: in vitro effects consistent
      with lack of in vivo toxicity in human chronic wounds.
AB  - BACKGROUND: Antiseptic agents, particularly slow-release preparations, are
      increasingly being used in the management of chronic wounds. One such agent,
      cadexomer iodine, carries iodine (0.9% weight/weight) immobilized in beads of
      dextrin and epichlorhydrin and has been demonstrated to be highly effective in
      promoting healing of exudative wounds. However, there have been no studies
      directly assessing the potential lack of toxicity of cadexomer iodine on human
      cutaneous tissues. OBJECTIVES: To determine if, within a certain concentration
      range, cadexomer iodine is non-toxic to human cells and cutaneous tissue and to
      assess histologically human chronic exudative wounds that are being treated with
      cadexomer iodine. METHODS: We examined the effects of varying concentrations of
      cadexomer iodine on the viability of human fibroblasts in culture (by trypan blue
      exclusion). The morphology, cellular proliferation capacity (measured by
      [3H]thymidine uptake), ability to produce alpha 1(I) procollagen chain mRNA, and
      cell outgrowth from neonatal foreskin explants were also evaluated in human
      fibroblasts after incubation with various concentrations of cadexomer iodine.
      Moreover, biopsies of chronic exudative wounds concurrently treated with
      cadexomer iodine were stained with haematoxylin and eosin or a Gram stain and
      evaluated microscopically. RESULTS: At concentrations of up to 0.45%, cadexomer
      iodine was found to be non-toxic to fibroblasts in vitro; there were no changes
      in viability, morphology, cellular proliferation, ability to produce collagen,
      and cell outgrowth from explants. In vivo, skin biopsies of chronic exudative
      wounds being treated with cadexomer iodine demonstrated no evidence of cell
      necrosis, displayed re-epithelialization, and revealed bacteria within the
      cadexomer beads. CONCLUSIONS: These studies demonstrate that cadexomer iodine has
      definite non-toxic concentration ranges for fibroblasts in vitro, which are
      consistent with a lack of cellular toxicity in human chronic exudative wounds
      treated with cadexomer iodine. Cadexomer iodine may also have the additional
      property of trapping microorganisms.

PMID- 11952537
TI  - Expression of nicotinic receptors in the skin of patients with palmoplantar
      pustulosis.
AB  - BACKGROUND: A suggested role for nicotine in the pathogenesis of palmoplantar
      pustulosis (PPP) has been discussed. The target for the inflammation in PPP is
      the acrosyringium. Nicotine acts as an agonist on nicotinic acetylcholine
      receptors (nAChRs) and can influence a variety of cellular functions. OBJECTIVES:
      To study the alpha 3- and alpha 7-nAChR expression in palmar skin of patients
      with PPP in comparison with that in healthy smoking and non-smoking controls.
      METHODS: Biopsies from 20 patients with PPP, seven healthy smokers and eight
      healthy non-smokers were studied by immunohistochemistry with a monoclonal anti
      alpha 3 and a polyclonal anti-alpha 7 antibody. RESULTS: In healthy controls both
      nAChR subtypes showed stronger immunoreactivity in the eccrine glands and ducts
      than in the epidermis. The papillary endothelium was positive for both subtypes.
      Epidermal alpha 3 staining was stronger and that of the coil and dermal ducts
      weaker in healthy smokers than in healthy non-smokers. In involved PPP skin,
      granulocytes displayed strong alpha 3 immunoreactivity. The normal epidermal
      alpha 7 staining pattern was abolished in PPP skin and was replaced by strong
      mesh-like surface staining, most markedly adjacent to the acrosyringium, which in
      controls was intensely alpha 7 positive at this level. Endothelial alpha 7
      staining was stronger in PPP skin than in the controls. CONCLUSIONS: Smoking can
      influence nAChR expression. The altered nAChR staining pattern in PPP skin may
      indicate a possible role for nicotine in the pathogenesis of PPP. We hypothesize
      that there is an abnormal response to nicotine in patients with PPP, resulting in
      inflammation.

PMID- 11952538
TI  - Changes in the distribution of laminin alpha1 chain in psoriatic skin:
      immunohistochemical study using confocal laser scanning microscopy.
AB  - BACKGROUND: Recent studies have demonstrated the presence in psoriatic skin of
      ultrastructural and molecular alterations in the basement membrane and an altered
      polarized distribution of the integrins. Previous studies have demonstrated the
      existence of some epithelial cell lines synthesizing only laminin beta and gamma
      chains that, in the absence of the laminin alpha chain, do not form a distinct
      basal lamina. OBJECTIVES: To investigate a possible reduction/absence of the
      laminin alpha 1 chain in keratinocytes in psoriatic skin and to correlate this
      with fibronectin distribution. METHODS: Using monoclonal antibodies against the
      laminin alpha1 chain or human plasma fibronectin and using confocal laser
      scanning microscopy, we evaluated the immunohistochemical expression of these two
      proteins in cutaneous biopsies from involved and uninvolved skin of the sacral
      region of 12 men with extensive chronic plaque psoriasis. Site-matched biopsies
      of normal skin from four men without psoriasis were used as controls. RESULTS: In
      normal skin antilaminin alpha 1 chain antibodies stained the dermal-epidermal
      junction in a regular and continuous manner. In involved and uninvolved psoriatic
      skin large regions of discontinuous immunostaining were observed, mainly at the
      apex of the dermal papillae; in the same regions, clusters of keratinocytes
      appeared markedly reactive and fibronectin was overexpressed in the papillary
      dermis under the interruptions of the basement membrane. CONCLUSIONS: The present
      study defines the location of the laminin alpha1 chain in involved and uninvolved
      psoriatic skin and suggests a possible role of the alteration of this chain,
      together with T-cell lymphokines and fibronectin, in the dysregulation of cell
      morphological processes.

PMID- 11952539
TI  - Quantitative in situ evaluation of telomeres in fluorescence in situ
      hybridization-processed sections of cutaneous melanocytic lesions and correlation
      with telomerase activity.
AB  - BACKGROUND: Telomere length is correlated with cellular ageing and
      immortalization processes. In some human cancers telomere length measurement has
      proved to be of diagnostic and prognostic value. Results comparable with the
      traditional terminal restriction fragment length determination by Southern
      blotting have been obtained in metaphase and interphase cells in some studies by
      fluorescence in situ hybridization (FISH) analysis; FISH additionally allows for
      the quantification of telomeres at the cellular level. OBJECTIVES: In this study,
      32 melanocytic lesions were analysed by FISH, aiming at investigating possible
      telomere differences among various benign and malignant lesions and correlation
      with telomerase activity (TA) level. METHODS: FISH was performed on paraffin
      sections from six common naevi, eight Spitz naevi, 12 melanomas, six melanoma
      metastases and nine control samples of normal skin. Telomere mean maximum
      diameter (Feret max), area and number per nuclear area were calculated by image
      analysis on fluorescent images elaborated through KS400 and in situ imaging
      system (ISIS) for FISH analysis programs. Mean TA level was also calculated in
      all lesions and correlated with telomere parameters. RESULTS: Telomere number per
      nuclear area was significantly lower in melanomas and metastases than in benign
      common and Spitz naevi and in control skin (7 small middle dot24 +/- 3.3; 6.11 +/
      3 vs. 14.46 +/- 5.6; 16.92 +/- 7.8; and 12.59 +/- 3.4, respectively; P < 0
      .001). No significant differences were found for the other telomere parameters.
      In common and Spitz naevi, telomere number was positively correlated with Feret
      max (P = 0.046 and P < 0.0001, respectively). TA was significantly higher in
      melanomas and metastases than in the other groups (70.18 +/- 25.2; 105.07 +/- 30
      vs. 2.16 +/- 2.4; 2 .99 +/- 2.1; 2 +/- 1.2, respectively; P< or = 0. 001) and it
      was inversely correlated with telomere number per nuclear area in melanomas (P =
      0.0041). No other significant correlations were found. CONCLUSIONS: Encouraging
      results have been obtained from quantitative telomere evaluation in the diagnosis
      of melanocytic lesions, although an analysis of a larger number of cases would be
      necessary to provide more reliable data. An extreme shortening of some telomeres
      probably results in the decrease of telomeric signals and the lower mean number
      of detectable telomeres in melanomas and metastases. In melanomas, telomere
      number per nuclear area is also inversely correlated with TA levels. Quantitative
      FISH of melanocytic lesions could give more specific information at the cellular
      level in telomere and telomerase fields of investigation.

PMID- 11952540
TI  - Cytokeratin expression in pilonidal sinus.
AB  - BACKGROUND: Pilonidal sinus (PS) is considered to belong in the category of
      follicular occlusion diseases (acne triad). OBJECTIVES: The aim of our study was
      to elucidate the pathogenesis of PS by evaluating its cytokeratin (CK)
      expression. METHODS: CK expression in nine cases of PS was studied
      immunohistochemically using six antikeratin antibodies. RESULTS: Infundibular
      like epithelium contained CK1, 10 and 14 similar to normal infundibulum, but it
      did not contain CK17. In non-infundibular-like epithelium, CK14, 16 and 17 were
      detected similar to that in normal outer root sheath. CK expression in PS was
      similar to that in hidradenitis suppurativa, suggesting that sinus epithelium may
      be fragile, hyperproliferative and undifferentiated. CONCLUSIONS: PS can be
      classified in the same entity as follicular occlusion diseases based on CK
      expression.

PMID- 11952541
TI  - Long-term efficacy and safety of tacalcitol ointment in patients with chronic
      plaque psoriasis.
AB  - BACKGROUND: As psoriasis patients often require continuous treatment optimal
      therapy has to provide efficacy and a good safety profile over the long term.
      OBJECTIVES: The aim of this multicentre study was to assess the efficacy, safety
      and tolerability of tacalcitol (4 microg g(-1)) ointment (Curatoderm, Hermal,
      Reinbek, Germany) applied once daily over a treatment period of 18 months.
      PATIENTS AND METHODS: Efficacy parameters were Psoriasis Area Severity Index
      (PASI), based on summed scores of erythema, infiltration and scaling and total
      body surface involvement (TBI). Safety assessment included serum levels of
      calcium, parathyroid hormone, calcitonin, 1,25-dihydroxy vitamin D3 (calcitriol);
      urinary calcium, creatinine, calcium/creatinine ratio in spot and 24-h urine and
      urinary alpha(1)-microglobulin. A group of 304 patients with chronic plaque
      psoriasis, covering between 7% and 20% of the body surface area was included for
      the initial treatment phase of 3 months. Of the 257 patients who completed the
      initial 3 months, 197 patients continued in a second treatment phase of 15
      months. RESULTS: Tacalcitol treatment proved to be effective in reducing the
      severity of psoriasis and maintained therapeutic response over the study period.
      The median PASI fell from 9.5 to 4 .6 at month 3 and to 3.25 at month 18 (P <
      0.0001). The median improvement in TBI was 30% at month 3 and 50% at month 18. In
      no patient was there any relevant disturbance of calcium homeostasis. There were
      no significant changes in mean values of serum calcium, parathyroid hormone and
      calcitriol. Additionally no significant changes in 24-h urinary excretion
      evaluation were observed. There was no correlation between levels of serum
      calcium or urinary calcium and amount of tacalcitol ointment used, even in the
      patients requiring the largest amounts of ointment (up to 13 g day(-1) and up to
      20% of body area affected). Treatment was generally well tolerated and there were
      no serious or unexpected adverse events reported. However, discontinuation of
      treatment as a result of skin irritation was seen in 5.9% of patients. The
      greatest frequency of cutaneous side-effects occurred during initial treatment
      and the incidence decreased markedly as the treatment was well-tolerated with
      continued use. CONCLUSIONS: Tacalcitol ointment once daily was demonstrated to be
      efficacious, safe and well tolerated in the long-term control of plaque psoriasis
      in patients with up to 20% body surface involvement.

PMID- 11952542
TI  - Oral zinc sulphate in the treatment of recalcitrant viral warts: randomized
      placebo-controlled clinical trial.
AB  - BACKGROUND: Viral warts are common dermatological diseases; although the rate of
      spontaneous recovery is high, it usually takes a long time, and some patients
      might not show this spontaneous healing. Zinc has an important effect on the
      immune system and it has been used as an immunomodulator to treat a variety of
      skin disorders. OBJECTIVE: To assess whether oral zinc was effective in treating
      viral warts of patients evaluated between May 1999 and April 2000. PATIENTS AND
      METHODS: This was a placebo-controlled clinical trial. Eighty patients with viral
      warts (common, plantar and plane) were all resistant to all forms of treatment.
      Each patient had > 15 warts. Forty patients were treated by oral zinc sulphate at
      a dose of 10 mg kg(-1) daily up to 600 mg day(-1) and followed-up for resolution
      of their warts and for any evidence of recurrence for 2-6 months. Another 40
      patients were given a placebo oral treatment in the form of glucose, and followed
      up for the same period. RESULTS: Only 23 patients of the first group (zinc
      treated) and 20 patients of the second group (placebo treated) completed the
      study. In all patients the serum level of zinc was low. In the zinc-treated
      group, the overall response was complete clearance of warts observed in 20
      patients (86.9%) after 2 months of treatment. Fourteen patients (60.9%) showed
      complete disappearance of their warts after 1 month. Three patients (13.3%)
      failed to respond to the treatment after 2 months of therapy. The response to
      treatment was directly related to the increment in serum zinc level. No patient
      of the placebo-treated group showed any response. CONCLUSIONS: We conclude that
      zinc sulphate at a dose of 10 mg kg(-1) daily seems to be a highly efficacious
      therapeutic option for recalcitrant viral warts and proved to be safe with few
      adverse effects.

PMID- 11952543
TI  - Randomized controlled trial of a single dermatology nurse consultation in primary
      care on the quality of life of children with atopic eczema.
AB  - BACKGROUND: Atopic eczema is mostly managed in primary care but there is often
      insufficient time for patient education; a nurse practitioner could help with
      this. OBJECTIVES: To evaluate the effects of a single consultation with a primary
      care nurse on the quality of life (QOL) of children with atopic eczema aged 0.5
      16 years and the impact of the disease on their families. PATIENTS AND METHODS:
      Children with eczema were invited to join the trial. Volunteers were randomized
      to a control group or an intervention group who attended the nurse for a single
      30-min session. Family impact was determined using the Family Dermatitis Index
      (FDI), and QOL was assessed using the Infant Dermatitis Quality of Life
      questionnaire (IDQOL) or, in children aged 4-16 years, the Children's Dermatology
      Life Quality Index (CDLQI). Baseline scores for family impact and QOL were
      compared with those at 4 weeks and 12 weeks post-intervention. RESULTS: Two
      hundred and thirty-five children were recruited over 12 months; 115 were aged 0.5
      4 years and 120 were aged 4-16 years. Follow-up data were missing for 38 children
      (84% completion rate, n = 197). All measures of QOL or family impact at baseline
      were skewed. The median scores were IDQOL, 5, and CDLQI, 6. About 20% of children
      had zero scores for the FDI (no impact on family life); median FDI scores were 2
      or 3. At baseline the FDI correlated with the IDQOL or CDLQI. In addition, the
      FDI and IDQOL were related to parental assessment of disease severity. Non
      responders had, on average, worse QOL at baseline than those who provided
      complete data. In the children with complete data, the mean differences in CD <
      Q1 and 1DQO< scores between intervention and control children were small at 4 and
      12 weeks (P > 0.05). The improvement in FDI at 4 weeks was slightly better in
      intervention than control children (P < 0.06). CONCLUSIONS: The impact on QOL of
      a single intervention by a dermatology nurse was marginal for family impact at 4
      weeks and was not apparent for other measures, either in the short or longer
      term. The planned sample size was derived from data in hospital patients but in
      our population disease activity was milder and the effects on QOL were less. On
      this account the present study was of low statistical power for some measures.
      Further studies in larger populations using additional outcome measures are
      required before advocating the wider introduction of nurse specialists.

PMID- 11952544
TI  - Willingness to pay and time trade-off: useful utility indicators for the
      assessment of quality of life and patient satisfaction in patients with port wine
      stains.
AB  - BACKGROUND: For cost utility analyses in health economic research it is necessary
      to assess quality of life for content validation. Previously, both quality of
      life questionnaires and utility indicators such as willingness to pay and time
      trade-off have been used successfully in patients with chronic skin diseases,
      such as psoriasis vulgaris or atopic eczema. OBJECTIVE: For the first time to
      assess willingness to pay and time trade-off in patients with port wine stains,
      and to study possible correlations between these indicators, patient income,
      quality of life questionnaires and subjective or objective outcome measures.
      METHODS: The results of a survey on 36 patients with facial lesions who had
      completed laser treatment were used for assessments. The 'Chronic Skin Disease
      Questionnaire' (CSDQ) and the 'Short Form-36 Health Survey' (SF-36) were used as
      quality of life questionnaires. Special questions were used as a basis for
      calculating the utility indicators, willingness to pay and time trade-off.
      RESULTS: Completed questionnaires were sent back by 25 patients (69%).
      Willingness to pay and time trade-off were used as instruments for the assessment
      of quality of life [questions answered by 23 (92% of respondents)]; patients were
      willing to pay 11.8% of their monthly income and would offer a mean value of 1.2
      h per day for an imaginary therapy leading to complete cure of the skin problem.
      Statistical correlation analyses were not performed because this pilot study
      included only a small number of patients. Frequency distributions show no
      apparent correlation between willingness to pay and patients' profession (used as
      a surrogate for income). Possible correlations were seen between willingness to
      pay, time trade-off, the scales 'anxiety/avoidance' and 'helplessness' of the
      CSDQ as well as 'social function' of SF-36 and subjective or objective efficacy.
      Twenty-nine patients (80%) were willing to pay for the treatment, a surrogate
      measure for patients' satisfaction with treatment modality. Overall, patients
      would pay an average of 16.0 euros per single treatment and 192.0 euros for the
      whole course of treatments. In contrast with patients who evaluated treatment
      modality as excellent or very good (willingness to pay for single treatment, euro
      22.0; for whole treatment, 270.0 euros), patients who judged treatment good (8.0
      euros, 145.0 euros), moderate or bad (12.0 euros, 146 .0 euros) were willing to
      pay markedly less. CONCLUSIONS: (i) The questions for willingness to pay and time
      trade-off were understood by most patients and produced meaningful answers. (ii)
      There were apparent correlations between the utility indicators, subjective or
      objective outcome and the scales of the quality of life questionnaires. (iii) The
      results show that these indicators have a high potential for use in this
      dermatological condition, especially as a basis for health economic evaluations.

PMID- 11952545
TI  - Spectrophotometric intracutaneous analysis: a new technique for imaging pigmented
      skin lesions.
AB  - BACKGROUND: Spectrophotometric intracutaneous analysis (SIA) is a new technique
      for imaging pigmented skin lesions and for diagnosing melanoma. The SIAscope
      produces eight narrow-band spectrally filtered images of the skin over an area of
      24 x 24 mm with radiation ranging from 400 to 1000 nm. OBJECTIVES: To present the
      early results of a clinical trial with SIA. METHODS: Spectrophotometric inputs
      from the skin were analysed using complex algorithms to return high-resolution
      information regarding total melanin content of the epidermis and papillary
      dermis, collagen and haemoglobin content as well as the presence of melanin in
      the papillary dermis. RESULTS: Simple, highly reproducible and reliable features
      were identified, e.g. the presence of dermal melanin, collagen holes and
      'erythematous blush' with blood displacement. These simple features were found to
      be highly specific (80.1%) and sensitive (82.7%) for melanoma in a dataset of 348
      pigmented lesions (52 melanomas) and compared very favourably with dermatoscopy
      when analysed using receiver-operator characteristic curves. CONCLUSIONS: This
      first clinical trial with SIAscopy has yielded very promising results and
      delivers new, useful information to the clinician diagnosing pigmented skin
      lesions.

PMID- 11952546
TI  - A cognitive-behavioural symptom management programme as an adjunct in psoriasis
      therapy.
AB  - BACKGROUND: Patients with psoriasis may experience significant psychological and
      social disabilities. Stress or distress are proposed aggravators of the disease
      process in psoriasis. Preliminary studies to date have suggested that adjunctive
      psychological therapies may be effective in the clinical management of psoriasis.
      OBJECTIVES: To examine whether a 6-week multidisciplinary management approach,
      the Psoriasis Symptom Management Programme (PSMP) for patients with psoriasis
      improves clinical severity of psoriasis and its associated psychological distress
      and disability. METHODS: In a case-control study, patients with psoriasis
      attending an out-patient psoriasis specialty clinic chose to receive standard
      psoriasis treatment alone (n = 53) or to enter the PSMP as an adjunct to standard
      therapy (n = 40). They were assessed at baseline, at the end of the 6-week PSMP
      and after 6 months follow-up. RESULTS: As compared with standard treatment alone,
      analysis of covariance indicated that participation in the PSMP resulted in a
      greater reduction in clinical severity of psoriasis (P = 0.001), anxiety (P =
      0.001), depression (P = 0.001), psoriasis-related stress (P = 0.001) and
      disability (P = 0.04) at 6 weeks and 6 months follow-up. CONCLUSIONS: The
      management of the physical aspects of psoriasis and its psychological effects are
      significantly improved for patients who opt for a 6-week integrated
      multidisciplinary approach. Furthermore, the techniques learnt by participation
      in the PSMP facilitate continued control of psoriasis for at least 6 months.

PMID- 11952547
TI  - Food-dependent exercise-induced anaphylaxis: influence of concurrent aspirin
      administration on skin testing and provocation.
AB  - BACKGROUND: Provocation tests in patients with food-dependent exercise-induced
      anaphylaxis (FDEIA) are often negative, even after a sufficient quantity of the
      implicated food and exercise have been taken. OBJECTIVES: To investigate the
      effect of aspirin in provocation tests and in skin prick testing (SPT) of
      patients with FDEIA. Gluten as a major allergen in wheat-dependent FDEIA was also
      investigated. METHODS: Provocation tests and SPT with suspected foods were
      performed in 12 patients with FDEIA. Provocation tests were performed with
      combinations of foods, exercise and aspirin. Detection of gluten-specific IgE was
      also performed by the CAP System FEIA radioallergosorbent test, SPT and a
      histamine release test. RESULTS: The SPT reaction was enhanced by pretreatment
      with oral aspirin in five of eight (62.5) patients. Aspirin facilitated
      provocation in five of seven (71%) patients tested. Ingestion of wheat and
      aspirin without exercise provoked symptoms in two patients. Aspirin provoked
      symptoms even with a small amount of wheat and exercise in one patient. Only the
      combination of aspirin, wheat and exercise provoked anaphylaxis in one patient.
      Specific IgE, SPT and/or the histamine release test with gluten were positive in
      nine of 11 patients with wheat-dependent FDEIA. CONCLUSIONS: Aspirin enhances
      symptoms of FDEIA, and prior ingestion of aspirin under controlled conditions can
      be used to confirm FDEIA. In practice, such patients should avoid aspirin
      ingestion. Gluten appears to be the major allergen in these patients with wheat
      dependent FDEIA.

PMID- 11952548
TI  - One-pass resurfacing with a combined-mode erbium: YAG/CO2 laser system: a study
      in 102 patients.
AB  - BACKGROUND: The CO2 and erbium: YAG (Er: YAG) lasers have been used for skin
      resurfacing. A recently developed system combines pulsed ablative Er: YAG and
      continuous wave subablative CO2 wavelengths in one console. OBJECTIVES: To assess
      the potential benefits of this system. METHODS: The study follows 102 women, skin
      types I-V, with 26 full face, 48 perioral and 28 periocular resurfacing
      procedures. The ablative Er: YAG pulse (350 micros, 29 J cm(-2)) is followed
      immediately by a non-ablative CO2 laser shot (4-6 W, 50 ms) through the same
      collimated handpiece (3-mm diameter spot), 50% overlapping, repetition rate 10
      Hz, giving two-pass equivalence with one single pass. RESULTS: Patients scored
      the results as very good (n = 67), good (n = 25) and fair (n = 10). Mild but
      successfully resolved side-effects occurred in only four patients. The 2-month
      histology showed a good band of new collagen tightening the overlying healthy
      epidermis. Follow-up periods ranged from 1.5 to 2 years (mean +/- SD 1.76 +/-
      0.33). CONCLUSIONS: This device at the above settings offers speedy resurfacing
      without compromising the quality of the procedure for the patient, and may well
      satisfy the basic requirements of laser skin resurfacing.

PMID- 11952549
TI  - The use of the dermatoscope to identify early melanoma using the three-colour
      test.
AB  - BACKGROUND: There is continuing interest in pre-operative evaluation of cutaneous
      pigmented lesions with the aim of differentiating early melanoma, which requires
      excision from non-melanomatous pigmented lesions that may safely be left
      untreated. OBJECTIVES: To establish, in the setting of a specialist pigmented
      lesion clinic, if use of the hand-held dermatoscope can prevent unnecessary
      excision of benign melanocytic pigmented lesions. METHODS: The study was carried
      out by three dermatologists experienced in the use of the dermatoscope. Patients
      had been referred by primary care physicians to the pigmented lesion clinic and
      had melanocytic lesions considered by dermatologists to merit excision on
      clinical grounds. A set of 74 sequentially observed lesions referred for
      excision, 37 melanomas and 37 melanocytic naevi, was used as the initial set and,
      thereafter, a second set of 52 lesions comprising 32 melanomas and 20 melanocytic
      naevi was used to validate conclusions drawn from the original set. Clinical
      features such as appearance and history, and also dermatoscope features were
      included in the assessment. RESULTS: In both sets of lesions, the most powerful
      identifying feature of lesions subsequently shown on pathological examination to
      be melanoma was the presence of three or more colours seen in the lesion on
      dermatoscopy. In the initial set of lesions, the age of the patient, an irregular
      edge and largest diameter of the lesion also contributed to diagnosis; however,
      in the second set of lesions these variables contributed little additional
      discriminatory value. The sensitivity and specificity of the three-colour
      dermatoscopy test for melanoma vs. naevus were 92% and 51%, respectively.
      CONCLUSIONS: The use of the dermatoscope three-colour test could reduce excision
      of benign melanocytic naevi by 50%, and thus prevent both unnecessary minor
      surgical workload and patient morbidity.

PMID- 11952550
TI  - Inhibition of ultraviolet B radiation-induced interleukin 10 expression in murine
      keratinocytes by selenium compounds.
AB  - BACKGROUND: Selenium is an essential trace nutrient necessary for the normal
      function of the immune system. Selenium compounds protect mice against
      ultraviolet (UV) B-induced tumours, probably by preventing oxidative damage to
      the host skin cells and to the host immune system. One possible mechanism of
      protection is that selenium can prevent oxidative stress-induced release of
      cytokines such as interleukin (IL)-10, which could suppress cell-mediated
      immunity. OBJECTIVES: To determine whether selenium compounds can inhibit UVB
      induction of IL-10 protein in murine keratinocytes. METHODS: The murine
      keratinocyte cell line PAM 212 was treated with or without selenomethionine (50
      200 nmol L-1) or sodium selenite (1-50 nmol L(-1)) for 24 h before exposure to
      200 J m(-2) UVB. The cells were stained with an antibody to IL-10, 24 h after
      irradiation. RESULTS: Preincubation with both selenium compounds inhibited UVB
      induction of IL-10 immunostaining, although selenomethionine was more effective.
      Pretreatment with 200 nmol L(-1) selenomethionine decreased IL-10 immunostaining
      to levels seen in the unirradiated controls. CONCLUSIONS: The protective effects
      of selenium against UVB-induced skin cancer in murine models may result, in part,
      from its ability to inhibit release of cytokines that are capable of suppressing
      cell-mediated immunity.

PMID- 11952551
TI  - Hereditary, focal, transgressive palmoplantar keratoderma with associated
      clinical findings: a new entity?
AB  - We report on a 24-year-old male originating from Yugoslavia with a focal,
      transgressive palmoplantar keratoderma presumably inherited as an autosomal
      recessive trait. Associated clinical findings were hyperkeratotic lichenoid
      papules on the knees and elbows, psoriasis-like lesions in the groins and on the
      scalp, a spotty or reticulate hyperpigmentation of the face, trunk and
      extremities and a partial alopecia of the left eyebrow and eyelashes. The
      patient's sister was affected by similar but less pronounced cutaneous changes.
      Although our case shares some similarities with other hereditary palmoplantar
      keratodermas there remain substantial differences. We therefore believe this case
      to represent a new entity.

PMID- 11952553
TI  - Linear and whorled naevoid hypermelanosis: a case with systemic involvement and
      trisomy 18 mosaicism.
AB  - We describe a 20-year-old woman with trisomy 18 mosaicism, who presented with
      skeletal anomalies, epilepsy, mental retardation, and linear and whorled naevoid
      hypermelanosis.

PMID- 11952552
TI  - Genetic analysis of a severe case of Netherton syndrome and application for
      prenatal testing.
AB  - Netherton syndrome (NS) is a rare autosomal recessive disease with variable
      expression. It is defined by a triad of symptoms: congenital ichthyosiform
      erythroderma, trichorrhexis invaginata and atopy. Recently, genetic linkage has
      been established to the SPINK5 gene locus on chromosome 5q32 encoding the serine
      protease inhibitor LEKTI. In this study, we present a recurrent homozygous
      mononucleotide deletion (153delT) resulting in a severe case of NS exhibiting
      exfoliative erythroderma with lethal outcome at the age of 4 months and its
      application in prenatal testing in a subsequent pregnancy of the mother.

PMID- 11952554
TI  - Epidermodysplasia verruciformis associated with neurofibromatosis type 1:
      coincidental association or model for understanding the underlying mechanism of
      the disease?
AB  - We describe a 25-year-old man with epidermodysplasia verruciformis (EV)
      associated with neurofibromatosis type 1 (NF1). The lesions, persisting for more
      than 15 years, consisted of widespread planar warts on the backs of the hands and
      wrists, and reddish-brown macules on the trunk, neck and face. During the last 5
      years, our patient developed several epithelial tumours, namely solar keratoses,
      plaques of Bowen's disease and squamous cell carcinomas (SCCs). He also presented
      with NF1 lesions with neurofibromas, cafe-au-lait macules, axillary freckling and
      Lisch nodules. He had left tibial bowing. Polymerase chain reaction analysis of
      the skin lesions demonstrated the presence of human papillomavirus (HPV) 15 in a
      flat wart, HPV 20 in a plaque of Bowen's disease, and HPV 15 and HPV 20 in an SCC
      lesion. Both EV and NF1 show an inherited predisposition to malignancy but the
      molecular mechanism underlying tumour development is not fully understood. The
      appearance of both diseases in our patient may be a coincidental association but
      may also contribute to the identification of loci for susceptibility to NF1 and
      EV on chromosome 17.

PMID- 11952555
TI  - Elevated serum caeruloplasmin level in a patient with adult Still's disease.
AB  - We report the case of a woman with a characteristic transient skin rash, fever,
      severe polyarthritis, hepatosplenomegaly, lymphadenopathy and myalgia. The
      clinical and laboratory data led to a diagnosis of adult-onset Still's disease.
      The elevated levels of serum ferritin and caeruloplasmin could be important as
      diagnostic indicators.

PMID- 11952556
TI  - Cholesterol embolization syndrome: cutaneous histopathological features and the
      variable onset of symptoms in patients with different risk factors.
AB  - Cholesterol embolization syndrome (CES) may not only be due to direct
      dislodgement of cholesterol crystals from atherosclerotic plaques on the walls of
      arteries by surgery, angiogram or trauma, but may occur after anticoagulant and
      thrombolytic therapy. The latter two therapies both weaken the fibrin clot that
      stabilizes the atheromas in place; however, these two therapies commonly have
      different onsets of CES after their institution. We present three patients with
      different risk factors for CES who all presented with the pathognomonic triad of
      leg and/or foot pain, livedo reticularis and good peripheral pulses. In all three
      patients cholesterol emboli were demonstrated in cutaneous biopsy sections. In
      two patients there was associated renal involvement, which was fatal in one case.
      These cases illustrate that cutaneous biopsy may be diagnostic in patients with
      livedo reticularis, which progresses to necrosis and gangrene. In addition, they
      illustrate the problems and contradictions involved in treating patients with
      CES.

PMID- 11952557
TI  - Local and systemic expression of basic fibroblast growth factor in a patient with
      familial glomangioma.
AB  - Glomangiomas are rare cutaneous tumours composed of glomus cells, which are
      modified smooth muscle cells. The aetiology of this condition is thought to
      involve a mutation in a novel gene acting to regulate angiogenesis. We report a
      patient from a large family with three generations affected by familial multiple
      glomangiomas. We hypothesized that the growth factors basic fibroblast growth
      factor and vascular endothelial growth factor, which stimulate/regulate
      angiogenesis could be involved in the pathogenesis of these lesions. Therefore,
      using enzyme-linked immunosorbent assays and immunohistochemistry, respectively,
      we measured systemic and tissue levels of these growth factors in a patient with
      familial glomangiomas. In addition, we investigated endothelial mitogenicity of
      the patient's serum as a functional assay of systemic growth factor activity.

PMID- 11952558
TI  - Eccrine poroma: another cause of a pigmented scalp nodule.

PMID- 11952559
TI  - Squamous syringometaplasia associated with docetaxel.

PMID- 11952560
TI  - Fixed drug eruption due to loratadine.

PMID- 11952561
TI  - Lupus vulgaris diagnosed after 87 years, presenting as an ulcerated 'birthmark'.

PMID- 11952562
TI  - Subclinical, primary antiphospholipid syndrome unmasked by sclerotherapy.

PMID- 11952563
TI  - Lymphoma molluscatum.

PMID- 11952564
TI  - Stealth triamcinolone acetonide in a phytocosmetic cream.

PMID- 11952565
TI  - A multiparametric approach is essential to define different clinicopathological
      entities within pseudopelade of Brocq.

PMID- 11952566
TI  - The use of intravenous phentolamine mesilate in the treatment of hyperhidrosis.

PMID- 11952567
TI  - Cytokeratin expression in steatocystoma multiplex.

PMID- 11952568
TI  - Applicability of reference values for the determination of serum S100 protein as
      a marker of malignant melanoma in children.

PMID- 11952569
TI  - Extensive erosive bullous pemphigoid: an atypical and serious clinical variant.

PMID- 11952571
TI  - Abstracts of the papers presented at the Annual Scientific Meeting of the British
      Society for Haematology. Brighton, United Kingdom, 15-18 April 2002.

PMID- 11952575
TI  - Quality of life after repair of bile duct injury.

PMID- 11952576
TI  - Ecosurgery.

PMID- 11952577
TI  - Positron emission tomography for staging and management of malignant melanoma.
AB  - BACKGROUND: The incidence of malignant melanoma is rising; it now has an
      incidence of ten per 100 000 per annum in the UK. The development of metastases
      is unpredictable, but prognosis is linked directly to the initial stage at
      diagnosis. Positron emission tomography (PET) can allow the detection of
      malignant cells at a relatively early stage. METHODS: A review of the literature
      was undertaken by searching the Medline database for the period 1980-2000 without
      any language restrictions. RESULTS: The overall sensitivity and specificity of
      PET are 74-100 and 67-100 per cent respectively. PET has a reduced sensitivity
      and specificity for thinner lesions (less than 1 x 5 mm). Comparison with
      computed tomography and magnetic resonance imaging has shown a higher sensitivity
      and specificity for PET in all regions of the body except the thorax. CONCLUSION:
      Currently the accepted indication for PET is recurrent melanoma when surgical
      intervention is being considered. However, other potential indications include
      the detection of occult or distant metastasis at initial presentation and the
      clarification of abnormal radiological findings at follow-up. The routine use of
      PET for American Joint Commission on Cancer stage I or II disease is of uncertain
      benefit and is not indicated at present.

PMID- 11952578
TI  - Acute compartment syndromes.
AB  - BACKGROUND: Acute compartment syndrome is both a limb- and life-threatening
      emergency that requires prompt treatment. To avoid a delay in diagnosis requires
      vigilance and, if necessary, intracompartmental pressure measurement. This review
      encompasses both limb and abdominal compartment syndrome, including aetiology,
      diagnosis, treatment and outcome. METHODS: A Pubmed and Cochrane database search
      was performed. Other articles were cross-referenced. RESULTS AND CONCLUSION:
      Diagnosis of limb compartment syndrome is based on clinical vigilance and
      repeated examination. Many techniques exist for tissue pressure measurement but
      they are indicated only in doubtful cases, the unconscious or obtunded patient,
      and children. However, monitoring of pressure has no harmful effect and may allow
      early fasciotomy, although the intracompartmental pressure threshold for such an
      undertaking is still unclear. Abdominal compartment syndrome requires measurement
      of intra-abdominal pressure because clinical diagnosis is difficult. Treatment is
      by abdominal decompression and secondary closure. Both types of compartment
      syndrome require prompt treatment to avoid significant sequelae.

PMID- 11952579
TI  - Randomized clinical trial assessing the side-effects of glyceryl trinitrate and
      diltiazem hydrochloride in the treatment of chronic anal fissure.
AB  - INTRODUCTION: Glyceryl trinitrate (GTN) ointment (0 small middle dot2 per cent)
      has an efficacy of up to 68 per cent in healing chronic anal fissure, but with
      headache as a major side-effect. Diltiazem hydrochloride (DTZ) cream (2 per cent)
      is expected to have fewer side-effects. METHODS: A prospective double-blind
      randomized two-centre trial requiring at least 26 patients in each group (alpha =
      0.05, beta = 0.9) was instituted after approval of the local ethics committee, to
      compare the incidence of side-effects (primary endpoint) with 0.2 per cent GTN
      ointment and 2 per cent DTZ cream in the treatment of chronic anal fissure.
      Treatments were applied perianally, twice daily for 6-8 weeks. All patients gave
      written informed consent. RESULTS: Both groups were comparable in patient
      demographics and clinical characteristics. Twelve patients violated the protocol,
      withdrew or did not attend follow-up. There were more side-effects with GTN (21
      of 29 patients) than with DTZ (13 of 31) (relative risk (RR) 1.84 (95 per cent
      confidence interval (c.i.) 1.11 to 3.04), P = 0.01). In particular, more
      headaches occurred with GTN (17 of 29 patients) than with DTZ (eight of 31) (RR
      2.06 (95 per cent c.i. 1.18 to 3.59), P = 0.01). There were no significant
      differences in healing and symptomatic improvement rates between patients
      receiving GTN (25 of 29) and DTZ (24 of 31). DISCUSSION: DTZ cream caused
      substantially fewer headaches than GTN ointment. There was no significant
      difference in the healing or improvement of chronic anal fissure between the
      treatments. DTZ may be the preferred first-line treatment for chronic anal
      fissure.

PMID- 11952580
TI  - Randomized clinical trial of long-term outcome after resection of hepatitis C
      virus-related hepatocellular carcinoma by postoperative interferon therapy.
AB  - BACKGROUND: Interferon therapy seems to decrease the incidence of recurrence
      after resection of hepatitis C virus (HCV)-related hepatocellular carcinoma
      (HCC). Effects of postoperative interferon therapy on the survival rate after
      resection of such HCC are still unclear. METHODS: A prospective randomized
      clinical trial of postoperative interferon therapy was performed. Thirty men were
      allocated randomly after liver resection to an interferon-alpha group (15
      patients) or a control group. Patients in the interferon group received
      interferon-alpha 6 MIU intramuscularly every day for 2 weeks, then three times a
      week for 14 weeks and finally twice a week for 88 weeks. RESULTS: The response to
      interferon was complete in two patients, there was a biochemical response in six
      patients and no response in seven patients. Interferon administration was not
      completed in three patients because of adverse events. Liver function did not
      change or worsened after operation in the control group, and did not change or
      improved in the interferon group. The cumulative survival rate was higher in the
      interferon group than in the control group (P = 0.041). CONCLUSION: Postoperative
      interferon therapy seems to improve the outcome after resection of HCV-related
      HCC.

PMID- 11952581
TI  - Randomized clinical trial of the effectiveness of emergency day surgery against
      standard inpatient treatment.
AB  - BACKGROUND: The aim of this study was to assess the feasibility of treating
      patients with minor and intermediate general surgical emergency conditions as day
      cases. METHODS: Emergency referrals for minor and intermediate general surgical
      conditions were assessed by a surgeon. Those fitting day-case criteria and
      requiring operation under general anaesthesia were randomized to receive standard
      inpatient care or day surgery. Patients in the latter group were booked on to day
      case lists or gaps on inpatient elective lists for surgery within 48 h. The
      process was coordinated by an experienced theatre sister. RESULTS: One hundred
      patients were randomized. There was a reduction in the number of nights spent in
      hospital in the day-case group (median 0 versus 2 nights; P < 0.001). The median
      time from diagnosis to treatment was 1 day in both groups, although there was a
      small but significant delay in the day-case group (P = 0.018). There was no
      significant difference in postoperative outcome or patient and general
      practitioner satisfaction. The day-case option had no increased impact on primary
      care services but was associated with a significant saving of about pound
      sterlings 150 per patient (P < 0.001). CONCLUSION: Certain general surgical
      emergencies may be managed as day cases with cost saving but without detriment to
      patient care.

PMID- 11952582
TI  - Randomized clinical trial of Ligasure versus conventional diathermy for day-case
      haemorrhoidectomy.
AB  - BACKGROUND: Haemorrhoidectomy is frequently associated with postoperative pain
      and prolonged hospital stay. A new technique of haemorrhoidectomy using the
      Ligasure device suited to day-case surgery is described. This technique was
      compared with conventional open diathermy haemorrhoidectomy. METHODS: Forty
      patients with grade III or IV haemorrhoids were randomized to Ligasure (group 1)
      or conventional diathermy (group 2) haemorrhoidectomy. Operative details were
      recorded and patients recorded daily pain scores on a linear analogue scale.
      Follow-up was at 1, 3, 6 and 12 weeks to evaluate complications, return to normal
      activity, ongoing symptoms and patient satisfaction. RESULTS: Reduced
      intraoperative blood loss (median (range) 0 (0-5) ml versus 20 (12-22) ml; P <
      0.001) and a shorter operating time (10 (8-11) versus 20 (18-25) min; P < 0.001)
      was observed in group 1 compared with group 2. More patients in group 1 were
      discharged on the day of operation (18 of 20 versus 11 of 20; P < 0.05) and there
      was a trend towards lower postoperative pain scores on day 1 (group 1 median 5
      (95 per cent confidence interval (c.i.) 2.6 to 6.8) versus group 2 7 (95 per cent
      c.i. 4.2 to 7.7); P = 0.36). There was no difference between the two groups in
      the degree of patient satisfaction or number of postoperative complications.
      CONCLUSION: Ligasure diathermy may be used safely in the treatment of patients
      with grade III or IV haemorrhoids. It reduces intraoperative blood loss and
      operating time, and facilitates same-day discharge.

PMID- 11952583
TI  - Comparison of magnetic resonance cholangiography and percutaneous transhepatic
      cholangiography in the evaluation of bile duct strictures after cholecystectomy.
AB  - BACKGROUND: Percutaneous transhepatic cholangiography (PTC) has been the
      preferred investigation to delineate the anatomy of the biliary tract in a
      patient with a bile duct stricture after cholecystectomy. Recently magnetic
      resonance cholangiography (MRC) has been described to evaluate the obstructed
      biliary tract. This paper reports a comparison of MRC with PTC in evaluating
      patients with an iatrogenic bile duct stricture. METHODS: This was a prospective
      study of 26 patients who had surgery for a bile duct stricture after
      cholecystectomy. Before operation all patients underwent both MRC and PTC, the
      results of which were compared with the intraoperative findings. RESULTS: Both
      PTC and MRC were comparable with regard to image quality, detection of
      intrahepatic bile duct dilatation, assessment of the level of injury and
      detection of abnormalities such as intraduct calculi, cholangitic liver abscesses
      and atrophy of liver lobes. MRC provided additional information in four patients,
      including detection of associated fluid collections (n = 3) and portal
      hypertension (n = 1). In eight patients more than one puncture had to be
      performed during PTC to delineate the complete anatomy. CONCLUSION: MRC is an
      accurate and non-invasive imaging procedure for preoperative evaluation of
      patients with a bile duct injury after cholecystectomy, and is capable of
      providing additional information which may not be available with PTC.

PMID- 11952584
TI  - Uptake of Lipiodol--cytotoxic conjugates by hepatoblastoma cells.
AB  - BACKGROUND: Improvements in the management of children with hepatoblastoma have
      followed advances made in cytotoxic agents and treatment regimens. The aim of
      this study was to quantify the effect of Lipiodol, an iodinated poppy-seed oil,
      on the uptake of anthracyclic cytotoxic conjugates by hepatoblastoma cells in
      culture. METHODS: Monolayer cultures of (1) a hepatoblastoma cell line generated
      from freshly explanted tumour tissue, (2) an immortal hepatoblastoma cell line
      (C3a) and (3) a human hepatocyte cell line were exposed to doxorubicin 10
      microg/ml with or without 2 per cent Lipiodol for 1-72 h. The fluorescence
      intensity in the treated cells, which correlates with intracellular doxorubicin
      concentration, was measured by confocal laser scanning microscopy. Cytotoxicity
      was assessed by trypan blue exclusion and electron microscopy. RESULTS:
      Doxorubicin accumulated in the nucleus and cytoplasm of all the cell lines. With
      Lipiodol, the mean fluorescence intensity of intracellular doxorubicin was
      increased for up to 48 h in both hepatoblastoma lines, but not in the hepatocyte
      cell line. Lipiodol increased the uptake and intracellular concentration of
      doxorubicin in the hepatoblastoma cells in culture. Lipiodol also enhanced the
      cytotoxicity of doxorubicin on the cultured hepatoblastoma cells. CONCLUSION:
      Lipiodol significantly enhanced the uptake of doxorubicin by hepatoblastoma cells
      in culture. Lipiodol-doxorubicin targeted treatment of hepatoblastoma may improve
      the intracellular uptake and hence cytotoxicity of doxorubicin in vivo, enabling
      a reduction in the total dose administered and side-effects.

PMID- 11952585
TI  - Surgical repair of ruptured thoracic and thoracoabdominal aortic aneurysms.
AB  - BACKGROUND: Rupture is the single most common cause of death in patients with
      thoracic aortic and thoracoabdominal aneurysm (TAA/TAAA) and is almost uniformly
      fatal. METHODS: This was a retrospective review of patients admitted to a single
      practice with rupture of a TAA/TAAA between 1993 and 2000. RESULTS: Twenty-two
      consecutive patients with a leaking TAA/TAAA were identified. The aetiology of
      rupture was either secondary to a degenerative TAAA or a type B dissection.
      Seventeen patients underwent surgery; one had a Crawford extent I, seven an
      extent II, one an extent III and two an extent IV TAAA. Six patients had an acute
      type B dissection with rupture in the upper descending thoracic aorta. The 30-day
      survival rate was 88 per cent (15 of 17 patients). Actuarial survival at 1 year
      in patients who had surgery was 65 per cent. Survival at 1 year for all
      presenting patients who consented to surgery was 40 per cent. Median survival was
      greater than 36 months. CONCLUSION: As a result of improving medical care, more
      patients with a contained rupture of a TAA/TAAA may present for treatment.
      Surgery is complex and requires specialist teams for optimal care.

PMID- 11952586
TI  - Accelerated postoperative recovery programme after colonic resection improves
      physical performance, pulmonary function and body composition.
AB  - BACKGROUND: Postoperative organ dysfunction contributes to morbidity, hospital
      stay and convalescence. Multimodal rehabilitation with epidural analgesia, early
      oral feeding, mobilization and laxative use after colonic resection has reduced
      ileus and hospital stay. METHODS: Fourteen patients receiving conventional care
      (group 1) and 14 patients who had multimodal rehabilitation (group 2) were
      studied before and 8 days after colonic resection. Outcome measures included
      postoperative mobilization, body composition by whole-body dual X-ray
      absorptiometry, cardiovascular response to treadmill exercise, pulmonary function
      and nocturnal oxygen saturation. RESULTS: Defaecation occurred earlier (median
      day 1 versus day 4) and hospital stay was shorter (median 2 versus 12 days) in
      patients who had multimodal treatment. Lean body and fat mass decreased in group
      1 but not in group 2. Exercise performance decreased by 44 per cent in group 1
      but was unchanged in group 2. A postoperative increase in heart rate (HR)
      response to exercise was avoided in group 2. Pulmonary function decreased in
      group 1 but not in group 2. There was less nocturnal postoperative hypoxaemia in
      group 2. Cardiac demand-supply (HR/oxygen saturation ratio) increased in group 1
      but not in group 2. CONCLUSION: Multimodal rehabilitation prevents reduction in
      lean body mass, pulmonary function, oxygenation and cardiovascular response to
      exercise after colonic surgery.

PMID- 11952587
TI  - Fate of the rectum in patients undergoing total colectomy for Crohn's disease.
AB  - BACKGROUND: This study aimed to analyse disease recurrence and fate of the rectum
      in patients who had a total colectomy for Crohn's disease. METHODS: One hundred
      and forty-four patients who had a total colectomy for Crohn's colitis were
      reviewed retrospectively. Ileorectal anastomosis (IRA) was performed in 118
      patients, while 26 never had an IRA after colectomy because of severe anorectal
      lesions. Factors associated with recurrence and rectal preservation failure were
      studied. RESULTS: The probability of clinical recurrence after IRA was 58 and 83
      per cent at 5 and 10 years respectively. The probability of rectal preservation
      at 5 and 10 years was 70 and 63 per cent after colectomy, and 86 and 86 per cent
      after IRA, respectively. Patients with extraintestinal manifestation had a higher
      risk of recurrence and of rectal preservation failure. Previous ileal involvement
      was associated with a higher rate of ileal recurrence after IRA. After IRA,
      prophylactic treatment with 5-aminosalicylic acid was associated with a lower
      rate of recurrence and of failure to preserve the rectum. CONCLUSION: Overall, 63
      per cent of patients had a functioning IRA 10 years after total colectomy.
      Absence of extraintestinal manifestation and prophylactic treatment with 5
      aminosalicylates after IRA were the main factors associated with long-term rectal
      preservation.

PMID- 11952588
TI  - Treatment of advanced gastric cancer by palliative gastrectomy, cytoreductive
      therapy and postoperative intraperitoneal chemotherapy.
AB  - BACKGROUND: The treatment options for the 10-20 per cent of patients with gastric
      cancer who present with peritoneal dissemination are extremely limited and no
      standard approach exists. METHODS: The feasibility of using intraperitoneal
      chemotherapy to treat gastric cancer with intra-abdominal gross residual lesions
      after palliative gastrectomy with maximal cytoreduction was investigated. Early
      postoperative intraperitoneal chemotherapy started on the day of operation with 5
      fluorouracil 500 mg/m2 and cisplatin 40 mg/m2 (days 1-3) over a 4-week interval.
      RESULTS: Of the 53 patients enrolled between July 1994 and December 1998, 49 were
      eligible. The progression-free survival (PFS) was 7 months and the overall
      survival was 12 months. In multivariate analysis, performance status was the only
      significant defining factor for PFS (P = 0.009). The predominant toxicity was
      neutropenia and nausea/vomiting. The relative dose intensity of 5-fluorouracil
      and cisplatin was 89 and 63 per cent respectively. CONCLUSION: Performance status
      emerged as a major determining factor for prognosis and patient selection for
      early postoperative intraperitoneal chemotherapy in patients with advanced
      gastric cancer after maximally cytoreductive surgery.

PMID- 11952589
TI  - Postoperative body-weight loss and survival after curative resection for gastric
      cancer.
AB  - BACKGROUND: Body-weight loss has been reported as a poor prognostic factor for
      some malignancies. The purpose of this study was to evaluate the prognostic value
      of postoperative body-weight loss in patients with gastric cancer. METHODS: In
      564 patients who underwent curative resection for gastric cancer, usual body
      weight, body-weight at the time of resection and that 6 and 12 months after
      resection were recorded prospectively. RESULTS: The 5-year survival rate of
      patients who lost more than 5 per cent of their 6-month postoperative weight by
      12 months after resection was 63 per cent while that of patients who maintained
      95 per cent or more of their 6-month postoperative weight was 84 per cent (P <
      0.001). Multivariate analysis revealed that serosal invasion, nodal metastasis,
      body-weight loss during the second 6-month interval after resection and extent of
      gastric resection were independent prognostic indicators. CONCLUSION: When a
      patient loses body-weight during the second 6-month interval after curative
      resection for gastric cancer, recurrent disease should be suspected.

PMID- 11952590
TI  - Impact of diagnostic laparoscopy on the management of gastric cancer: prospective
      study of 120 consecutive patients with primary gastric adenocarcinoma.
AB  - BACKGROUND: Peritoneal seeding or liver metastases found at laparotomy usually
      preclude curative treatment in patients with gastric adenocarcinoma. Such
      exploratory laparotomies may be avoided by diagnostic laparoscopy. However,
      routine diagnostic laparoscopy does not benefit those patients who proceed to
      laparotomy after negative laparoscopy. The aim of this study was to evaluate
      prospectively the selective use of laparoscopy in uncertain situations. METHODS:
      One hundred and twenty consecutive patients with primary gastric adenocarcinoma
      were studied prospectively. Diagnostic laparoscopy was performed in patients with
      clinical T4 tumours or suspected metastases, unless laparotomy was required for
      symptomatic disease. RESULTS: Ninety-six of 120 patients were selected for
      immediate laparotomy with curative intent (n = 81) or for palliation (n = 15). In
      two of the 81 patients gastrectomy was abandoned because of unexpected peritoneal
      carcinomatosis. Fifteen patients underwent diagnostic laparoscopy, which
      identified intra-abdominal metastases in six; the other nine patients proceeded
      to laparotomy, which revealed peritoneal metastases not detected at laparoscopy
      in four patients. The remaining nine patients had overt metastases and were
      referred for systemic chemotherapy without abdominal exploration. CONCLUSION:
      Diagnostic laparoscopy in selected patients effectively limits the number of
      unnecessary invasive staging procedures. Routine use of diagnostic laparoscopy in
      all patients with gastric adenocarcinoma is not warranted.

PMID- 11952591
TI  - Results of laparoscopic Nissen fundoplication at 2-8 years after surgery.
AB  - BACKGROUND: Although the long-term results of open fundoplication for gastro
      oesophageal reflux disease are well documented, there have been few reports of
      the long-term results of laparoscopic fundoplication. METHODS: Between January
      1993 and July 1999, 179 consecutive patients underwent laparoscopic floppy Nissen
      fundoplication. Of these, 175 were available for long-term follow-up. Structured
      symptom questionnaires were completed by 140 patients (80 per cent) at 2-5 years
      (n = 92) or 5-8 years (n = 48) after operation. RESULTS: Patient satisfaction
      with surgery was 91 per cent at a median follow-up of 48 (range 24-99) months.
      Visick scores of I or II were recorded by 84 per cent. Ninety per cent of
      patients remained free from significant reflux symptoms. Side-effects were common
      (22 per cent) but rarely affected patient satisfaction. Of the 19 patients (14
      per cent) taking regular antireflux medication, eight used it for non-reflux
      symptoms and 12 had normal postoperative pH tests. CONCLUSION: Laparoscopic
      floppy Nissen fundoplication is an effective and durable treatment for gastro
      oesophageal reflux disease. Longer-term follow-up of patients operated on beyond
      the learning curve can be expected to show further improvements in surgical
      outcome.

PMID- 11952592
TI  - Diethylmaleate, a pro-oxidant, attenuates experimental ischaemia-reperfusion
      induced lung injury.
AB  - BACKGROUND: Systemic ischaemia-reperfusion (IR) injury is in part an oxidant
      injury mediated by neutrophils. Diethylmaleate (DEM), an intracellular pro
      oxidant agent, has been shown to alleviate neutrophil-mediated tissue injury. The
      aim of this study was to evaluate whether DEM could have a protective effect on
      neutrophil-mediated lung injury in an animal model of lower-torso IR. METHODS:
      Sprague-Dawley rats (seven per group) were randomized into three groups. The
      control group underwent midline laparotomy only; the IR group underwent
      laparotomy and clamping of the infrarenal abdominal aorta for 30 min followed by
      2 h of reperfusion; and the third group was pretreated with DEM 6 mmol/kg
      intraperitoneally 1 h before the IR insult. RESULTS: IR resulted in a significant
      increase in both microvascular leakage and pulmonary neutrophil infiltration as
      measured by bronchoalveolar lavage protein concentration and pulmonary
      myeloperoxidase activity respectively. Pretreatment with DEM significantly
      attenuated both microvascular leakage and neutrophil infiltration. CONCLUSION:
      Preconditioning with DEM protected against IR-induced lung injury. This
      protective effect raises the possibility of using pro-oxidants to prevent
      inflammatory injury.

PMID- 11952593
TI  - Risk of femoral hernia after inguinal herniorrhaphy.
AB  - BACKGROUND: Small case series have suggested an increased risk of femoral hernia
      after previous inguinal herniorrhaphy, but no large-scale data with complete
      follow-up are available. METHODS: Data were extracted from the Danish Hernia
      Database covering the interval from 1 January 1998 to 1 July 2001, and included
      34 849 groin hernia repairs. RESULTS: Of 1297 femoral hernia repairs, 71 patients
      had previously had an operation for inguinal hernia within the observation
      period. These 71 femoral hernias represented 7.9 per cent of all reoperations for
      groin hernia recorded in the database. The median time to reoperation for a
      'recurrent' femoral hernia after previous inguinal herniorrhaphy was 7 months,
      compared with 10 months for inguinal recurrences. The risk of developing a
      'recurrent' femoral hernia after previous inguinal herniorrhaphy was 15 times
      higher than the rate of femoral hernia repair in the general population.
      CONCLUSION: This study of 34 849 groin hernia repairs demonstrated a 15-fold
      greater incidence of femoral hernia after inguinal herniorrhaphy compared with
      the spontaneous incidence. These femoral recurrences occurred earlier than
      inguinal recurrences, suggesting that they were possibly femoral hernias
      overlooked at the primary operation.

PMID- 11952595
TI  - Intragastric balloon in the treatment of patients with morbid obesity.

PMID- 11952596
TI  - Gender differences in long-term survival of patients with colorectal cancer.

PMID- 11952597
TI  - Gender differences in long-term survival of patients with colorectal cancer.

PMID- 11952598
TI  - Gender differences in long-term survival of patients with colorectal cancer.

PMID- 11952600
TI  - Randomized double-blind controlled trial of roxithromycin for prevention of
      abdominal aortic aneurysm expansion.

PMID- 11952601
TI  - Late mortality in patients with severe acute pancreatitis.

PMID- 11952603
TI  - Randomized double-blind controlled trial of roxithromycin for prevention of
      abdominal aortic aneurysm expansion.

PMID- 11952604
TI  - Effect of Helicobacter pylori eradication on the ulcer recurrence rate after
      simple closure of perforated duodenal ulcer: retrospective and prospective
      randomized controlled studies.

PMID- 11952605
TI  - Effect of Helicobacter pylori eradication on the ulcer recurrence rate after
      simple closure of perforated duodenal ulcer: retrospective and prospective
      randomized controlled studies.

PMID- 11952608
TI  - Effect of adenosine on ischaemia-reperfusion injury associated with rat pancreas
      transplantation.

PMID- 11952609
TI  - Prospective analysis of quality of life and survival following mesorectal
      excision for rectal cancer.

PMID- 11952610
TI  - Stoma related complications are more frequent after transverse colostomy than
      loop ileostomy: a prospective randomized clinical trial.

PMID- 11952611
TI  - Effect of multimodality therapy on ciculating vascular endothelial growth factor
      levels in patients with oesophagal cancer.

PMID- 11952613
TI  - Estimating the benefits of adjuvant systemic therapy for women with early breast
      cancer.

PMID- 11952614
TI  - Randomized clinical trial of the effect of open versus laproscopically assisted
      colectomy on systemic immunity in patients with colorectal cancer.

PMID- 11952615
TI  - Randomized clinical trial of the effect of open versus laproscopically assisted
      colectomy on systemic immunity in patients with colorectal cancer.

PMID- 11952616
TI  - Readmissions after pancreatoduodenectomy.

PMID- 11952617
TI  - Endovascular treatment of abdominal aortic aneurysm: a failed experiment.

PMID- 11952618
TI  - Endovascular treatment of abdominal aortic aneurysm: a failed experiment.

PMID- 11952620
TI  - Endovascular treatment of abdominal aortic aneurysm: a failed experiment.

PMID- 11952621
TI  - Endovascular treatment of abdominal aortic aneurysm: a failed experiment.

PMID- 11952623
TI  - Endovascular treatment of abdominal aortic aneurysm: a failed experiment.

PMID- 11952636
TI  - Molecular and cellular determinants of non-typeable Haemophilus influenzae
      adherence and invasion.
AB  - Non-typeable Haemophilus influenzae is a common cause of human disease and
      initiates infection by colonizing the upper respiratory tract. Based on
      information from histopathologic specimens and in vitro studies with human cells
      and tissues in culture, non-typeable H. influenzae is capable of efficient
      adherence and appreciable invasion, properties that facilitate the process of
      colonization. A number of adhesive factors exist, each recognizing a distinct
      host cell structure and influencing cellular binding specificity. In addition, at
      least three invasion pathways exist, including one resembling macropinocytosis, a
      second mediated via the PAF receptor and a third involving beta-glucan receptors.
      Organisms are also capable of disrupting cell-cell junctions and passing between
      cells to the subepithelial space.

PMID- 11952637
TI  - Yersinia effectors target mammalian signalling pathways.
AB  - Animals have an immune system to fight off challenges from both viruses and
      bacteria. The first line of defence is innate immunity, which is composed of
      cells that engulf pathogens as well as cells that release potent signalling
      molecules to activate an inflammatory response and the adaptive immune system.
      Pathogenic bacteria have evolved a set of weapons, or effectors, to ensure
      survival in the host. Yersinia spp. use a type III secretion system to
      translocate these effector proteins, called Yops, into the host. This report
      outlines how Yops thwart the signalling machinery of the host immune system.

PMID- 11952638
TI  - The EspB protein of enterohaemorrhagic Escherichia coli interacts directly with
      alpha-catenin.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) belongs to a family of pathogens that
      cause attaching and effacing (A/E) lesion on target cells. The EspB protein of
      EHEC is translocated both to the host cell cytoplasm and to the membrane, and is
      essential for the signalling events leading to A/E lesion. To determine the
      actual role of EspB in this process, we tried to identify the EspB binding
      partner of the host cell protein, using a yeast two-hybrid assay, and obtained a
      cytoskeletal-associated protein, alpha-catenin. The alpha-catenin bound directly
      to the N-terminal region of EspB, both in solid (overlay assay) and solution
      (pull-down assay) phases, and it was recruited to the EHEC adherence site,
      dependent on EspB. Expression of the N-terminal region of EspB, as well as the
      whole EspB in host cells, inhibited F-actin accumulation on the adherence site.
      We conclude that EspB recruits alpha-catenin at the EHEC adherence site by direct
      interaction, and that the recruitment of alpha-catenin is essential for EHEC
      induced A/E lesion formation.

PMID- 11952639
TI  - Neural Wiskott-Aldrich syndrome protein (N-WASP) is the specific ligand for
      Shigella VirG among the WASP family and determines the host cell type allowing
      actin-based spreading.
AB  - Shigella, the causative agent of bacillary dysentery, is capable of directing its
      movement within host cells by forming an actin comet tail. The VirG (IcsA) pro
      tein expressed at one pole of the bacterium recruits neural Wiskott-Aldrich
      syndrome protein (N-WASP), a member of the WASP family, which in turn stimulates
      actin-related protein (Arp) 2/3 complex-mediated actin polymerization. As all the
      WASP family proteins induce actin polymerization by recruiting Arp2/3 complex, we
      investigated their involvement in Shigella motility. Here, we show that VirG
      binds to N-WASP but not to the other WASP family proteins. Using a series of
      chimeras obtained by swapping N-WASP and WASP domains, we demonstrated that the
      specificity of VirG to interact with N-WASP lies in the N-terminal region
      containing the pleckstrin homology (PH) domain and calmodulin-binding IQ motif of
      N-WASP. A conformational change in N-WASP was important for the VirG-N-WASP
      interaction, as elimination of the C-terminal acidic region, which is responsible
      for the intramolecular interaction with the central basic region of N-WASP,
      affected the specific binding to VirG. We observed that, in haematopoietic cells
      such as macrophages, polymorphonuclear leucocytes (PMNs) and platelets, WASP was
      predominantly expressed, whereas the expression of N-WASP was greatly suppressed.
      Indeed, unlike Listeria, Shigella was unable to move in macrophages at all,
      although the movement was restored as N-WASP was expressed ectopically. Thus, our
      findings demonstrate that N-WASP is a specific ligand of VirG, which determines
      the host cell type allowing actin-based spreading of Shigella.

PMID- 11952640
TI  - Enteropathogenic Escherichia coli induces modification of the focal adhesions of
      infected host cells.
AB  - Enteropathogenic Escherichia coli (EPEC) is a human-specific pathogen that causes
      severe diarrhoea in young children. The disease involves intimate interaction
      between the pathogen and the brush border of enterocytes. During infection, EPEC
      uses a type III secretion system (TTSS) to inject several proteins into the
      infected cells, and these effector proteins modify specific processes in the host
      cell. We show that, upon infection, EPEC induces detachment of the infected host
      cells from the substratum, modification of focal adhesions (FA) in the infected
      cells and specific dephosphorylation of focal adhesion kinase (FAK). We also show
      that EPEC-induced cell detachment is dependent on FAK expression by the infected
      cells. Finally, we demonstrate that cell detachment, FA modification and FAK
      dephosphorylation are dependent on functional TTSS in the infecting EPEC. These
      results suggest that EPEC is using its TTSS to inject protein(s) into the
      infected cells, which can induce FAK dephosphorylation, as well as FAK-dependent
      FA modification and cell detachment. These processes are specific and probably
      play an important role in EPEC virulence.

PMID- 11952642
TI  - X-irradiation effects on thymidine kinase (TK): I. TK1 and 2 in normal and
      malignant cells.
AB  - The effect of radiation on TK is more complicated than would be expected from
      earlier results on bone marrow cells (Feinendegen et al. 1984, Int. J. Radiat.
      Biol. 45, 205). TK activity increased at 0.01 Gy and then decreased up to 1 Gy in
      mouse spleen. In contrast to the results for the spleen, an increase in activity
      at 0.1 Gy was seen in mouse thymus. The activity of dephosphorylated TK1 (TK1a)
      in both spleen and thymus was reduced to 50% after irradiation at 0.5-1 Gy. The
      degree of phosphorylation (TK1b/TK1a ratio) changed in spleen, but not in thymus.
      The activity of TK2 in mouse liver increased at 3 h after 5 Gy by about 60%. In
      mouse ascites tumour, a dose-independent (1-5 Gy) oscillating TK1 activity was
      found up to 24 h, especially for TK1a and TK1b. The amount of TK1 was unchanged
      up to 12 h, but decreased at 24 h. This suggests that the differences in the
      changes in the degree of phosphorylation of TK1 after irradiation among spleen,
      thymus and ascites tumour further underline the complexity of the response of TK1
      activity to irradiation. The dramatic change in the activities of TK1a and TK1b
      may illustrate that both of them are more radiosensitive than TK-h, a variant
      with mixed TK1 and TK2 properties.

PMID- 11952641
TI  - Functional studies of the recombinant subunits of a cytolethal distending
      holotoxin.
AB  - Cytolethal distending toxin (CDT) is a multicomponent bacterial holotoxin that
      targets most eukarytotic cells causing distension and cell cycle arrest. A number
      of diverse pathogenic bacterial species associated with diarrhoea, chancroid,
      chronic hepatitis and periodontal disease produce a CDT. Synthesis of the
      holotoxin is directed by the expression of three genes, cdtA, cdtB and cdtC.
      Although the product of the CdtB gene was previously identified as a type I
      deoxyribonuclease, the functions of the cdtA and cdtC products have not been
      characterized. Using the periodontal pathogen, Actinobacillus
      actinomycetemcomitans, we demonstrate that the recombinant product of the CdtA
      gene binds to the surface of Chinese hamster ovary (CHO) cells. This protein did
      not induce distension or cytotoxicity when introduced into the cytosol using a
      lipid-based protein delivery system. Recombinant CdtB and CdtC proteins failed to
      bind to CHO cells. However, the delivery of either CdtB or CdtC into the cytosol
      resulted in the characteristic pattern of distension followed by cell death.
      Based on these results, it appears that the CdtA protein subunit alone is
      responsible for anchoring the holotoxin to the cell surface. The CdtC subunit, in
      concert with CdtB, contributes to the cytotoxic activities of the holotoxin. The
      specific mechanism of CdtC cytotoxicity is currently unknown.

PMID- 11952643
TI  - X-irradiation effects on thymidine kinase (TK): II. The significance of
      deoxythymidine triphosphate for inhibition of TK1 activity.
AB  - The purpose of this study was to investigate the mechanism behind the high
      sensitivity of thymidine kinase 1 (TK1) to X-irradiation. The deoxythymidine
      triphosphate (dTTP) pool was studied in mouse ascites tumour cells 1-24 h after X
      irradiation with 5 Gy. Irradiation changed the Michaelis-Menten kinetics of TK1
      from linear to biphasic, showing a negative co-operativity. These changes were
      closely related to changes in the dTTP pool. Addition of dTTP to the cell extract
      of non-irradiated cells, or thymidine (dTdR) to the culture medium, resulted in
      changes very similar to the kinetics found in the irradiated cells. Addition of 5
      cent-amino-5 cent-deoxythymidine (5 cent-AdTdR), a thymidine analogue that
      eliminated the inhibitory effect of dTTP on TK1 activity, completely abolished
      the irradiation-induced inhibition of TK1 activity. We suggest that the reduced
      TK1 activity is mainly due to an elevated intracellular concentration of dTTP.

PMID- 11952644
TI  - G2-phase radiation response in lymphoblastoid cell lines from Nijmegen breakage
      syndrome.
AB  - The relationship between G2-phase checkpoint activation, cytoplasmic cyclin-B1
      accumulation and nuclear phosphorylation of p34CDC2 was studied in Nijmegen
      breakage syndrome cells treated with DNA damaging agents. Experiments were
      performed on lymphoblastoid cell lines from four Nijmegen breakage syndrome
      patients with different mutations, as well as on cells from an ataxia
      telangiectasia patient. Lymphoblastoid cell lines were irradiated with 0.50-2 Gy
      X-rays and the percentage of G2-phase accumulated cells was evaluated by means of
      flow cytometry in samples that were harvested 24 h later. The G2-checkpoint
      activation was analysed by scoring the mitotic index at 2 and 4 h after treatment
      with 0.5 and 1 Gy X-rays and treatment with the DNA double-strand break inducer
      calicheamicin-gamma1. Cytoplasmic accumulation of cyclin-B1 was evaluated by
      means of fluorescence immunostaining or Western blotting, in cells harvested
      shortly after irradiation with 1 and 2 Gy. The extent of tyrosine 15
      phosphorylated p34CDC2 was assessed in the nuclear fractions. Nijmegen breakage
      syndrome cells showed suboptimal G2-phase checkpoint activation respect to normal
      cells and were greatly different from ataxia telangiectasia cells. Increased
      cytoplasmic cyclin-B1 accumulation was detected by both immunofluorescence and
      immunoblot in normal as well as in Nijmegen breakage syndrome cells. Furthermore,
      nuclear p34CDC2. phosphorylation was detected at a higher level in Nijmegen
      breakage syndrome than in ataxia telangiectasia cells. In conclusion, our data do
      not suggest that failure to activate checkpoints plays a major role in the
      radiosensitivity of Nijmegen breakage syndrome cells.

PMID- 11952645
TI  - Inhibition of human neuroblastoma cell proliferation and EGF receptor
      phosphorylation by gangliosides GM1, GM3, GD1A and GT1B.
AB  - The inhibitory action of gangliosides GT1B, GD1A, GM3 and GM1 on cell
      proliferation and epidermal growth factor receptor (EGFR) phosphorylation was
      determined in the N-myc amplified human neuroblastoma cell line NBL-W. The IC50
      of each ganglioside was estimated from concentration-response regressions
      generated by incubating NBL-W cells with incremental concentrations (5-1000
      microm) of GT1B, GD1A, GM3 or GM1 for 4 days. Cell proliferation was
      quantitatively determined by a colourimetric assay using tetrazolium dye and
      spectrophotometric analysis, and EGFR phosphorylation by densitometry of Western
      blots. All gangliosides assayed, with the exception of GM1, inhibited NBL-W cell
      proliferation in a concentration-dependent manner. The IC50s for gangliosides
      GT1B [molecular weight (MW) 2129], GM3 (MW 1236), and GD1A (MW 1838) were (mean
      +/- SEM) 117 +/- 26, 255 +/- 29, and 425 +/- 44 m, respectively. In contrast, the
      IC50 for GM1 (MW 1547) could not be determined. Incubation of NBL-W cells with
      epidermal growth factor (EGF) concentrations ranging from 0.1 to 1000 ng/ml
      progressively increased cell proliferation rate, but it plateaued at
      concentrations above 10 ng/ml. EGFR tyrosine phosphorylation, however, was
      incrementally stimulated by EGF concentrations from 1 to 100 ng/ml. The
      suppression of EGF-induced EGFR phosphorylation differed for each ganglioside,
      and their respective inhibitory potencies were as follows: EGFR phosphorylation
      [area under curve (+ EGF)/area under curve (- EGF)]: control (no ganglioside
      added) = 8.2; GM1 = 8.3; GD1A = 6.7; GM3 = 4.87, and GT1B = 4.09. The lower the
      ratio, the greater the inhibitory activity of the ganglioside. Gangliosides GD1A
      and GT1B, which have terminal N-acetyl neuraminic acid moieties, as well as one
      and two N-acetyl neuraminic acid residues linked to the internal galactose,
      respectively, both inhibited cell proliferation and EGFR phosphorylation.
      However, GD1A was a more potent suppressor of cell proliferation and GT1B most
      effective against EGFR phosphorylation. GM3, which only has a terminal N-acetyl
      neuraminic acid, inhibited cell proliferation and EGFR phosphorylation almost
      equivalently. These data suggest that gangliosides differ in their potency as
      inhibitors of NBL-W neuroblastoma cell proliferation and EGFR tyrosine
      phosphorylation, and that perturbations in the differential expression of
      membrane glycosphingolipids may play a role in modulating neuroblastoma growth.

PMID- 11952646
TI  - Exogenous cysteine and cystine promote cell proliferation in CaCo-2 cells.
AB  - Previous studies have shown that intracellular glutathione, a ubiquitous
      intracellular thiol, is related to cell proliferation and that cysteine or its
      disulphide form, cystine, also induces cell proliferation. Cysteine is a thiol
      containing amino acid and a rate-limiting precursor of glutathione. Therefore, it
      is still unresolved as to whether the proliferative effect of cysteine or cystine
      is entirely mediated by a change in the intracellular glutathione status. The
      objective of this study was to delineate the relationship among cysteine/cystine
      (thereafter referred to as cyst(e)ine), intracellular glutathione and cell
      proliferation in the human colon cancer CaCo-2 cell line. CaCo-2 cells were
      cultured in cyst(e)ine-free Dulbecco's Modified Eagle Medium without serum, and
      treated with 200 microm cysteine and/or 200-400 microm cystine for 24 h. In the
      presence of DL-buthionine-[S, R]-sulfoximine (BSO), a glutathione synthesis
      inhibitor, exogenously administered cyst(e)ine did not change the intracellular
      glutathione content, but increased the intracellular cysteine as well as cystine
      level. Addition of exogenous cyst(e)ine following 5 mm BSO treatment
      significantly increased cell proliferation as measured by 3H-thymidine
      incorporation and protein content. Cell cycle analyses revealed that cyst(e)ine
      promoted cell progression from the G1 phase to the S phase. Correspondingly,
      cyst(e)ine treatment induced expression of cyclin D1 and phosphorylation of
      retinoblastoma protein (Rb). In conclusion, these data indicate that both
      cysteine and cystine have proliferative effects in CaCo-2 cells independent of an
      increase in intracellular glutathione. Induction of cyclin D1, phosphorylation of
      Rb, and subsequent facilitation of G1-to-S phase transition were involved in the
      proliferative effect of exogenous cyst(e)ine.

PMID- 11952647
TI  - Facilitating factors and barriers to the implementation of intensive home-based
      behavioural intervention for young children with autism.
AB  - BACKGROUND: Although international interest in intensive home-based early
      behavioural intervention for children with autism is increasing, there is little
      or no published research on the experiences of families conducting these
      programmes. METHODS: One hundred and forty-one UK parents conducting Lovaas-style
      interventions with their young child with autism were asked to identify factors
      that acted as facilitative factors and barriers to the implementation of these
      programmes. Parents responded to written questions contained within a
      questionnaire survey, and their responses were subjected to a content analysis
      procedure. RESULTS: Several of the facilitative factors and barriers were found
      to be similar. For example, a supportive therapy team was the most frequently
      cited facilitative factor, and problems recruiting and maintaining a suitable
      team was the most frequently reported barrier. Other factors seemed to be more
      independent constructs. For example, an important barrier was the lack of time
      and personal energy, but plenty of time and energy was not cited as a
      facilitative factor. CONCLUSIONS: The practical implications of these results for
      families and for services supporting families engaged in intensive early
      behavioural intervention are discussed. In addition, more general implications
      for the designers of behavioural intervention programmes are identified.

PMID- 11952648
TI  - Child psychiatric skills in primary healthcare--self-evaluation of Finnish health
      centre doctors.
AB  - OBJECTIVE: To study Finnish general practitioners' (GP's) perceptions of their
      child psychiatric skills. METHODS: The study sample consisted of physicians
      (n=755) working in health centres situated in the special response area of the
      Tampere University Hospital, Finland. They were requested to assess their
      competence in 16 areas on a four-step Likert scale. The response rate was 66.1%
      (n=499). RESULTS: Physicians evaluated their child psychiatric skills as
      inadequate on many issues. The ability to identify depression was poorer the
      younger the child in question. Only a minority (14%) felt they were well able to
      identify a depressed infant. Many physicians considered themselves poorly skilled
      in assessing the relationship between infant and parents (39.8%), in assessing a
      child's need for psychiatric treatment (42.7%) and in identifying a child with
      attention-deficit disorder (40.7%). A majority (75.9%) rated their skills poor in
      co-operating with daycare personnel or school staff in matters concerning a child
      with conduct disturbance. Only 26.8% could assess the necessity of taking a child
      into custody. Women gave higher ratings of their skills in identifying depressed
      infants and in assessing the infant-parent relationship than men, whereas men
      assessed their skills as better in cases in which there were problems in co
      operation with parents. CONCLUSIONS: In order to provide good psychiatric
      services for children, attention should be paid to the GPs' child psychiatric
      skills.

PMID- 11952650
TI  - Parenting behaviour described by mothers in a general population sample.
AB  - OBJECTIVES: To collect mothers' reports of the range of behaviours used by them
      in the management of their children's difficult behaviour. DESIGN: A cross
      sectional study using an interview with both semi-structured and open-ended
      question routes. SAMPLING FRAME: The population of mothers with 10-year-old
      children living in the New Forest region of Hampshire, UK. METHODS: Mothers
      (n=67), selected from the sampling frame, were interviewed about the range of
      parenting behaviours they used in the management of their children's difficult
      behaviour. RESULTS: Mothers reported a wide range of behaviours. Both
      authoritative (e.g. reasoning was mentioned by 42%) and authoritarian (e.g. the
      use of physical punishment was mentioned by 37%) behaviours were mentioned
      frequently. Although the different behaviours within these domains were
      intercorrelated, there was little overlap between the two domains. The use of
      praise for good behaviour seemed to be independent of other behaviours. There was
      no association between mothers' parenting behaviours and the behaviour problems
      of their children. CONCLUSIONS: These data suggest that parenting takes many
      forms, with variations of behaviour across the 'normal' range being unlikely to
      represent a significant risk to children's development. Public funding for
      parenting education should be targeted at those children who are at significant
      risk from extreme forms of parenting.

PMID- 11952649
TI  - Variations in the orthotic management of cerebral palsy.
AB  - OBJECTIVE: Anecdotal reports that children with cerebral palsy were provided
      different orthoses in two adjacent UK health districts were investigated using an
      observational comparative case study. METHOD: The populations were compared using
      an epidemiological register of children with cerebral palsy, which confirmed that
      a comparable health service response could be expected. Merging data from the
      register with the orthotic patient database facilitated comparison of the
      orthoses prescribed in each district. A survey questionnaire was used to gather
      the perceptions of clinicians in both districts to understand how each team
      decides which orthosis to prescribe. RESULTS: There was considerable variation in
      the types of orthoses prescribed between districts, and particularly of ankle
      foot orthoses. Survey respondents from the same profession described having the
      same roles, although clinicians expressed different responsibilities for
      initiating and sanctioning orthotic prescriptions in their district programmes.
      The survey also suggested that most clinicians were uncertain when prescribing
      orthoses, and clinical practice was therefore largely determined by professional
      preference. CONCLUSION: Defining the spectrum of activity limitation in
      geographically defined populations would enhance health services research and
      assist in the development of trials using different interventions to reduce those
      limitations.

PMID- 11952651
TI  - Use of chopsticks in Chinese children.
AB  - OBJECTIVE: There has been no study on the developmental stage of acquiring the
      skill of using chopsticks, which is a common eating tool of the Orientals. We
      aimed to obtain a developmental profile for achieving the skills of chopsticks
      manipulation in Chinese children and to assess the correlation between chopsticks
      manipulation and the level of achieving independence in 'eating' item in the
      Functional Independence Measure of children (WeeFIM). We also studied the
      relationship between demographic and environmental factors and the age of
      achieving chopstick manipulation. METHODS: Direct interview with the mothers of
      445 non-disabled children who were randomly selected from the community. A
      chopsticks score (CS) of 1 was defined as children who could use chopsticks to
      finish more than half the meal, and a CS of 0 as failure to do so. RESULTS: The
      mean age of achieving a CS of 1 was 4.6 years. At 6.7 years, all these children
      achieved this skill. There was a significant relationship between age of
      achieving the skills of chopsticks and the level of attaining independence in
      'WeeFIM eating' score. (P < 0.001) However, there was no correlation of age of
      achieving CS of 1 with sex, social class or the presence of a domestic helper.
      CONCLUSION: Most non-disabled Chinese children can achieve the visual motor skill
      of using chopsticks at 4.6 years. There was also a correlation with the age of
      achieving independence in the WeeFIM eating score. The skill of using chopsticks
      should be added as part of the tools, apart from spoons or forks, for scoring
      WeeFIM in Chinese children.

PMID- 11952652
TI  - A dose-response relationship between short sleeping hours and childhood obesity:
      results of the Toyama Birth Cohort Study.
AB  - BACKGROUND: Short sleeping hours could cause obesity through increased
      sympathetic activity, elevated cortisol secretion and decreased glucose
      tolerance. The aim of this study was to clarify parental and lifestyle factors,
      particularly sleeping habits, associated with obesity in Japanese children.
      METHODS: Between June and July 1996, 8274 children (4194 males and 4080 females)
      aged 6-7 years living in Toyama prefecture, Japan, were investigated by
      questionnaire survey and the collection of anthropometric data. Subjects with a
      body mass index (BMI; weight in kg divided by square of height in m) greater than
      the age- and sex-specific cut-off points linked to adulthood overweight (BMI of
      25 kg/m2 or more) were defined as obese subjects. Parental obesity was defined as
      a BMI of 25 kg/m2 or more. Logistic regression analysis was performed to evaluate
      the strength of the relationships between parental obesity or lifestyle factors
      and childhood obesity, adjusted for possible confounding factors. RESULTS:
      Parental obesity, long hours of TV watching and physical inactivity were
      significantly associated with childhood obesity. Although wake-up time was not
      related to obesity, there was a significant dose-response relationship between
      late bedtime or short sleeping hours and childhood obesity. Compared with
      children with 10 or more hours of sleep, the adjusted odds ratio was 1.49 (95%
      confidence interval 1.08-2.14) for those with 9-10 h sleep, 1.89 (1.34-2.73) for
      those with 8-9 h sleep and 2.87 (1.61-5.05) for those with <8 h sleep, after
      adjustment for age, sex, parental obesity and other lifestyle factors.
      CONCLUSION: A strong inverse association was observed in the relationship between
      sleeping hours and childhood obesity. Longitudinal research will be required to
      confirm this causality.

PMID- 11952653
TI  - Experience of respiratory and allergic illness in children attending childcare.
AB  - OBJECTIVES: To describe previous illness for children attending two types of
      formal childcare (130 family daycare homes and 11 child daycare centres). DESIGN:
      A questionnaire was completed by the parents of 846 children, which provided
      information about previous illness and associated factors. The questionnaire was
      conducted in Perth, Western Australia. RESULTS: Of all children, 39% had
      experienced otitis media, 11% glue ear and 26% allergies; 18% had been diagnosed
      with asthma; 10% had been admitted to hospital with respiratory illness, and 9%
      had experienced more than six respiratory conditions in the previous year.
      Attending centre daycare compared with family daycare was more likely to be
      associated with some of the previous illness outcomes (more than six respiratory
      illnesses in the past year, asthma, otitis media and glue ear) but, for all
      children, the major predisposing factors associated with these illnesses were a
      family history of atopy or bronchitis. CONCLUSIONS: Children with a history of
      respiratory illness or otitis media are more likely to be attending centre than
      family daycare, but family history of respiratory illness is an important risk
      factor for all children in childcare.

PMID- 11952654
TI  - Management of hip dislocation with postural management.
AB  - BACKGROUND: Hip dislocation in children with cerebral palsy has a well-documented
      history and morbidity. OBJECTIVE: This paper presents a retrospective study of
      children with bilateral cerebral palsy who had various postural management and
      its effect on hip deformity. The most widely accepted theoretical model of hip
      subluxation/dislocation is that an imbalance in muscle length and strength around
      the hip leads to acetabular dysplasia and consequent hip subluxation. Maintenance
      of muscle length and strength and loadbearing is therefore a logical prevention.
      Research on normal infants' postures has provided biomechanical data to form the
      theoretical basis of 24 h postural management equipment. METHODS: The notes and X
      rays of 59 children with bilateral cerebral palsy from East and West Sussex and
      Oxfordshire were examined and measured to determine whether a relationship
      existed between postural management and the level of hip subluxation/dislocation.
      X-rays were measured using Reimers' hip migration percentage. Postural management
      support was divided into three groups for analysis. Category 1: use of a 24-h
      postural management approach using Chailey Adjustable Postural Support (CAPS)
      systems in lying, sitting and standing; category 2: two items of CAPS (either
      lying/sitting or sitting/standing supports); category 3: use of the CAPS seat
      only and/or any other postural supports. Hip status was recorded for analysis as
      both hips safe (under 33% migrated), or one/both hips subluxed. RESULTS: Children
      using 'All CAPS' before hip subluxation maintained significantly more hip
      integrity than other groups (chi2 P < 0.05). CONCLUSIONS: Postural management
      interventions have an important role in the prevention of hip dysplasia.

PMID- 11952659
TI  - A review of high-dose intravenous immunoglobulin treatment for atopic dermatitis.
AB  - Atopic dermatitis generally responds to topical therapy; however, small numbers
      of patients have severe resistant disease despite second line therapies. High
      dose intravenous immunoglobulin (HdIVIg) which is being used increasingly for
      dermatological indications has been suggested to be of benefit in a small number
      of uncontrolled trials and case reports. The mode of action is via a number of
      immunomodulatory mechanisms and it is not associated with the many side-effects
      of steroids and other immunosuppressive agents. There are now reports of 32
      atopic dermatitis patients treated with HdIVIg, and this review aims to make a
      critical assessment of the current data. These have been obtained from a Medline
      search of the English literature from 1966 to 2001 for intravenous immunoglobulin
      and atopic dermatitis/eczema. Taken together an improvement was observed in 61%
      of atopic dermatitis patients treated with HdIVIg. Adults appeared less likely to
      respond (48%) than children (90%) and the duration of response was also more
      prolonged in children. Adjunctive therapy in adults was more effective than
      monotherapy (59% vs 0%), whereas monotherapy was effective in 90% of children.
      HdIVIg may offer a safe potential therapeutic avenue for resistant cases of
      atopic dermatitis, particularly in children, but should be further assessed using
      double-blind placebo-controlled trials.

PMID- 11952660
TI  - Mucocutaneous adverse effects of hydroxyurea: a prospective study of 30 psoriasis
      patients.
AB  - Hydroxyurea is an anti-tumour agent most commonly used to treat chronic
      myeloproliferative disorders in doses up to 4 g per day. Dermatological adverse
      effects reported so far have been observed predominantly in these patients. As we
      are treating selected psoriasis patients with low dose hydroxyurea we attempted
      to define the spectrum and chronology of dermatological adverse effects in this
      group of patients prospectively. Of the 29 evaluable patients, 19 (65.5%)
      developed a mucocutaneous adverse reaction after a mean duration of 6.4 weeks of
      treatment. Pigmentation of nails, skin or mucosa was the most common observation
      and was seen in 17 (58.6%) patients. Other less common findings were xerosis,
      diffuse alopecia, oedema of the legs, oral ulcers and actinic psoriasis. Adverse
      effects subsided in 11 (57.9%) patients during a mean follow up of 18 weeks.
      Three hitherto unreported side-effects - scleral pigmentation, acquired
      ichthyosis and pigmentation of lunula of the nails - were noted. This first study
      of dermatological adverse effects of hydroxyurea therapy on Asian psoriatic
      patients reveals several new findings. Pigmentation of skin, nails and mucosa
      appears to be very common and occurs early. Serious dermatological side-effects
      probably do not occur with low dose (up to 1.5 g per day) hydroxyurea in patients
      with psoriasis.

PMID- 11952662
TI  - A previously unreported syndrome of multiple scalp whorls and associated
      anomalies.
AB  - A 13-month-old male infant with 14 hair whorls in the scalp, sparse frontal hair,
      wide forehead, ectropion, abnormal implantation of eyelashes, peculiar face and
      depigmented nipples is reported. Other aspects of his physical and mental
      development were within normal limits. The constellation of clinical features in
      this patient appear to represent a previously undescribed syndrome.

PMID- 11952661
TI  - A comparison of the efficacy and safety of mupirocin cream and cephalexin in the
      treatment of secondarily infected eczema.
AB  - The efficacy and safety of mupirocin calcium cream were compared with those of
      oral cephalexin in the treatment of secondarily infected eczema. In this
      multicentre, double-blind, double-dummy study, 159 patients with secondarily
      infected eczema (suitable for treatment with topical antimicrobials) and a total
      skin infection rating scale score of 8 or more were randomized to receive either
      topical mupirocin cream three times daily or oral cephalexin, 250 mg four times
      daily, for 10 days (intent-to-treat group). Clinical success (per-protocol
      group), defined in part as a patient with a response of improvement in the skin
      infection rating scale, was similar in the two groups: 89% for mupirocin (n = 44)
      and 82% for cephalexin (n = 38) [P = 0.29; 95% confidence interval (-8.4%,
      22.5%)]. Bacteriological success (intent-to-treat group), defined as a patient
      with a response of eradication, improvement or colonization of bacteria at the
      end of therapy, however, was significantly higher for mupirocin [50% and 28% in
      the mupirocin (n = 48) and cephalexin (n = 47) groups, respectively; P=0.005].
      Mupirocin cream was as well tolerated as cephalexin; 9% and 13% of patients
      reported adverse events related or possibly related to study medication in the
      mupirocin and cephalexin groups, respectively. The most common adverse events
      overall were diarrhoea and nausea. Mupirocin cream applied three times daily is
      as effective clinically and superior bacteriologically compared with oral
      cephalexin given four times daily in the treatment of secondarily infected eczema
      of limited depth and severity. Mupirocin cream is as well tolerated as oral
      cephalexin, and more patients prefer the topical regimen, which should improve
      patient compliance.

PMID- 11952663
TI  - Linear IgA disease in a patient with Castleman's disease.
AB  - Linear IgA disease (LAD) is a well recognized subepidermal blistering disorder
      characterized by linear deposits of IgA at the basement membrane zone. The
      aetiology is unknown but there is a recognized association with
      lymphoproliferative malignancies. We report a case of LAD occurring in a patient
      with multicentric Castleman's disease (angiofollicular lymph node hyperplasia),
      an association not previously recorded in the literature.

PMID- 11952664
TI  - Becker's naevus of the thigh with lipoatrophy: report of two cases.
AB  - Although Becker's naevus is most common in males, cases with associated
      lipoatrophy are more frequently reported in women. Two women are described in
      whom Becker's naevus of the thigh was associated with localized lipoatrophy.
      Neither had any bony abnormality or functional deficit.

PMID- 11952665
TI  - Reactivity to autologous serum skin test and clinical features in chronic
      idiopathic urticaria.
AB  - The autologous-serum skin test (ASST) can cause a wheal-and-flare response in
      some cases of chronic idiopathic urticaria. We subjected 102 patients affected by
      chronic idiopathic urticaria to this test and studied some clinical parameters to
      detect any significant differences between ASST-positive and ASST-negative
      patients. The only significant difference we noted between the two groups was the
      incidence of angioedema (P = 0.01). We suggest that the ASST cannot be used alone
      either to predict the severity of urticaria or to define it as 'autoimmune'.

PMID- 11952666
TI  - A boy with cutaneous necrosis occurring during treatment with levamisole.
AB  - We present a child on long-term treatment with levamisole, and heterozygous for
      factor V Leiden, who developed cutaneous necrosis associated with formation of p
      ANCA and lupus anticoagulant. Symptoms resolved when the levamisole treatment was
      stopped.

PMID- 11952667
TI  - Etizolam-induced superficial erythema annulare centrifugum.
AB  - Erythema annulare centrifugum (EAC) is characterized by slowly enlarging annular
      erythematous lesions. Although the origin is not clear in most cases, EAC has
      been associated with infections, medications, and in rare cases, underlying
      malignancy. We describe a patient who developed annular erythematous lesions
      after etizolam administration. The eruptions were typical of the superficial form
      of EAC, both clinically and histopathologically. The lesions disappeared shortly
      after discontinuation of the medication. Patch testing with etizolam gave
      positive results. To our knowledge this is the first reported case of etizolam
      induced superficial EAC.

PMID- 11952668
TI  - Long-term follow-up of a patient with cutaneous vasculitis secondary to mixed
      cryoglobulinaemia and hepatitis C virus.
AB  - We describe the clinical course of a patient with mixed cryoglobulinaemia and
      multisystem disease over a 21-year period. She consistently tested negative for
      hepatitis C virus (HCV) serology, but active HCV infection (genotype Ia) was
      confirmed using reverse transcription-polymerase chain reaction. After initial
      improvement following treatment with interferon-alpha and ribavirin,
      unfortunately she developed severe neutropenia necessitating discontinuation of
      both drugs within 4 weeks. She died 1 month later.

PMID- 11952669
TI  - New laboratory techniques for the assessment of acquired immunobullous disorders.
AB  - This review aims to summarize investigations that are used in the assessment of
      patients with suspected immunobullous disorders. Emphasis is placed upon new
      adaptations of existing techniques and the advent of recombinant technology,
      which has enabled the production of synthetic antigens. The use of recombinant
      antigens has provided the latest generation of diagnostic techniques that are
      likely to make a major impact on routine diagnosis of immunobullous disorders.

PMID- 11952670
TI  - Efficacy of topical corticosteroids in nickel-induced contact allergy.
AB  - In this study we used the nickel contact allergy patch (CAP) test to investigate
      the effect of topical corticosteroids on allergic contact dermatitis (ACD). On
      day 1, three CAP tests were applied for 48 h on the forearms of 20 female
      volunteers with a known nickel ACD. CAP of the right forearm contained 5% nickel,
      and of the left forearm physiological saline. Clinical scoring, transepidermal
      water loss and skin hydration were measured on day 1 before CAP application, on
      day 4 (0, 2 and 6 h) after ACD and from days 5 to 8 (0 h). A topical
      corticosteroid and its vehicle were applied twice daily starting from day 4 on
      two ACD sites. Transepidermal water loss values were significantly decreased on
      the topical-corticosteroid-treated sites in the early phase of ACD (day 4, 6 h
      after the first application) while clinical efficacy showed significant
      improvement on days 7 and 8. The vehicle was found to improve skin hydration only
      on day 8. In conclusion the topical corticosteroid improved the skin barrier
      function in the early inflammatory phase of ACD (day 4, 6 h). The lack of
      improvement in transepidermal water loss in the later phase of ACD might be
      accounted for by the secondary effects of the corticosteroid on proliferation and
      differentiation of keratinocytes.

PMID- 11952671
TI  - The effect of wound ointments on tissue microcirculation and leucocyte behaviour.
AB  - An intact microcirculation is essential for normal healing to occur. Wound repair
      may be impaired by various endogenous and exogenous factors, such as reduced
      microvascular perfusion, infection and debris. In the nonhealing wound, radical
      surgical debridement is critical. To supplement healing, various ointments are
      used in clinical practice. Little is known about their effects on tissue
      perfusion. We have therefore selected two substances widely used, the antiseptic
      Betadine and the enzyme combination Elase and investigated their impact on the
      microcirculation and on leucocyte activity, using the cremaster muscle as a
      model. We found that functional capillary density and arteriolar diameters were
      significantly reduced by Betadine, whereas leucocyte activity was not affected.
      In the Elase group, capillary flow and arteriolar diameters were significantly
      increased, and again leucocyte activity was not changed. The mechanism by which
      Betadine reduces microvascular flow is believed to be the same as in reperfusion
      injury. The positive effect of Elase on the microcirculation might be attributed
      to plasmin, which has been shown to dilate blood vessels.

PMID- 11952672
TI  - A Japanese case of de novo dominant dystrophic epidermolysis bullosa.
AB  - We report a Japanese case of dominant dystrophic epidermolysis bullosa with a de
      novo mutation in the triple-helical domain of the type VII collagen. Mutation
      detection revealed a glycine --> aspartic acid substitution at amino acid
      position 2012 in exon 73 (G2012D). This previously unreported mutation underlies
      a clinical phenotype of moderately severe, localized skin blistering.

PMID- 11952673
TI  - Antineutrophil cytoplasmic antibodies in patients with systemic lupus
      erythematosus.
AB  - We determined the prevalence of antineutrophil cytoplasmic antibodies (ANCAs) in
      patients with systemic lupus erythematosus (SLE) and evaluated the correlation
      between ANCA positivity and clinical features. Forty-one patients with SLE and
      two control groups were examined. One of the control groups consisted of 15
      patients with systemic vasculitis, and the other of 12 healthy blood donors. A
      quantitative enzyme-linked immunosorbent assay technique was used to measure the
      serum cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA) levels. cANCA
      positivity was found in three patient samples, and pANCA positivity in 10 SLE
      patients. The occurrence and titres of both ANCA types in SLE patients were
      similar to those in healthy controls and significantly lower than those in
      patients with systemic vasculitis. The clinical picture and antibody profile were
      similar in ANCA-positive and ANCA-negative SLE patients. We conclude that
      measurement of ANCAs does not provide any additional diagnostic or prognostic
      data in SLE.

PMID- 11952674
TI  - Acrodermatitis enteropathica - lifelong follow-up and zinc monitoring.

PMID- 11952675
TI  - Cutaneous metastasis of prostate carcinoma.

PMID- 11952676
TI  - Mycosis fungoides masquerading as tinea of the axilla.

PMID- 11952677
TI  - The scrotum: an unusual site for basal cell carcinoma.

PMID- 11952678
TI  - Acute perianal streptococcal infection in an adult.

PMID- 11952680
TI  - Meyerson's phenomenon around a seborrhoeic keratosis.

PMID- 11952679
TI  - Trauma-induced bullous pemphigoid around venous access site in a haemodialysis
      patient.

PMID- 11952681
TI  - Widespread bullous eruption due to multiple bed bug bites.

PMID- 11952682
TI  - Traumatic neuroma following a human bite.

PMID- 11952683
TI  - Case 1. Systematic lupus erythematosus (SLE).

PMID- 11952684
TI  - Case 2. Infantile eosinophilic pustular folliculitis (IEPF).

PMID- 11952685
TI  - Case 3. Scarring from previous acne vulgaris. Basal cell carcinoma (BCC).

PMID- 11952686
TI  - Case 4. Chronic urticaria due to strongyloidiasis.

PMID- 11952688
TI  - Atopic dermatitis - a simple entity?

PMID- 11952687
TI  - Mellanby on scabies.

PMID- 11952689
TI  - On dermatological surgery, registrars and residents.
AB  - Training in aspects of skin surgery is now a requirement of general dermatology
      registrars and residents in the UK and USA, respectively. We compare this
      component of the training programmes at St John's Institute of Dermatology in
      London and at New York Medical College in New York City. Because of their
      understanding of cutaneous pathology, dermatologists are often best qualified to
      assess patients for skin procedures and should therefore be involved, directly or
      indirectly, in their surgical management. In our view, the curricula should be
      changed to place more emphasis on the supervised assessment and treatment of
      patients with skin tumours as well as to reflect the growing importance of laser
      treatments and the demand by patients for cosmetic interventions.

PMID- 11952698
TI  - Coal tar: past, present and future.
AB  - Crude coal tar has been used in the treatment of dermatoses for many decades. In
      the last few years its use has been limited to skin diseases such as psoriasis
      and chronic dermatitis. Newer topical modalities for psoriasis are being used
      increasingly for treatment, but have failed to replace crude coal tar as a first
      line treatment of psoriasis. We review the pharmacology, chemistry and use of
      crude coal in order to reappraise its role as a therapeutic agent in dermatology.

PMID- 11952699
TI  - Psoralen photochemotherapy (PUVA) is only moderately effective in widespread
      vitiligo: a 10-year retrospective study.
AB  - A 10-year retrospective analysis of the use of psoralen photochemotherapy (PUVA)
      in the treatment of vitiligo was undertaken at the St John's Institute of
      Dermatology, London, UK. Of 97 patients included in this study, eight had
      complete or almost complete repigmentation, 59 moderate to extensive
      repigmentation, and 30 showed little or no response. However, 24 of those who had
      responded to PUVA with extensive repigmentation did not consider their response
      satisfactory because of persistence of vitiligo at cosmetically sensitive sites,
      and poorly matching, speckled repigmentation. Fifty-seven patients who initially
      improved with PUVA therapy subsequently relapsed, in most cases within a year of
      stopping treatment. Relapses in 22 patients were on the same cutaneous sites as
      previously affected, while vitiligo at new sites developed in 20 patients and
      both new and old sites were affected in a further 15 patients. Patients who
      retained their pigmentation after 2 years appeared to have a better chance of
      permanent remission. The only statistically significant prognostic indicator of
      relapse was patient age at the start of treatment, younger patients tending to
      retain their pigmentation longer than older patients. This study emphasizes the
      need for careful patient counselling before PUVA therapy as this treatment seldom
      achieves extensive repigmentation that is cosmetically acceptable, and treatment
      response is often followed by relapse.

PMID- 11952700
TI  - Adverse effects with long-term cyclosporin for severe psoriasis.
AB  - The use of cyclosporin A (CSA) for the treatment of severe psoriasis is well
      established. However its use is limited by its adverse effects, especially
      nephrotoxicity. We reviewed 28 patients treated with CSA for severe psoriasis
      over an 11-year period. All patients were on long-term CSA treatment (median
      duration 55.5 months). Twenty patients developed renal impairment which required
      discontinuation of treatment in seven. Twelve patients' renal function stabilized
      on dose reduction and one improved. Sixteen patients developed hypertension. For
      this small group of patients with severe psoriasis, recalcitrant to other
      treatments, CSA afforded better quality of life which they otherwise could not
      enjoy. Although this comes at a cost with the development of renal impairment we
      feel that such patients can be continued on CSA provided that they are under the
      combined care of a dermatologist and a nephrologist.

PMID- 11952701
TI  - Generalized lichen nitidus.
AB  - We report a 38-year-old man who presented with a generalized papular eruption
      that was clinically and histologically consistent with lichen nitidus. This
      patient's condition had been persistent for approximately 1 year; however, soon
      after assuming employment that entailed significant, regular sun exposure, the
      patient noted marked clearing of his lesions in sun-exposed areas. This case
      corroborates previous reports that suggest that generalized lichen nitidus can be
      successfully managed with ultraviolet light therapy.

PMID- 11952702
TI  - Periungal hyperpigmentation induced by cisplatin.
AB  - A number of anticancer drugs are known to produce pigmentary changes affecting
      the skin or nails. Among them, cisplatin (cis-diamminedichloroplatinum)-induced
      hyperpigmentation has been described previously in only two cases. We describe an
      unusual case with hyperpigmentation confined to periungal areas of the hands and
      feet after treatment with cisplatin.

PMID- 11952703
TI  - Cutaneous dissemination of nasal NK/T-cell lymphoma with bone marrow, liver and
      lung involvement.
AB  - We describe a 32-year-old Korean man with a primary nasal natural killer (NK)/T
      cell lymphoma (NKTCL). Combination chemotherapy and radiotherapy resulted in
      initial complete remission. However, cutaneous dissemination to the trunk and
      proximal extremities occurred 16 months later and further investigations revealed
      involvement of the liver, lymph nodes, lung and bone marrow. Nasal CD56+ NKTCL is
      mostly localized to the nasal area but also shows a predilection for other sites,
      such as skin. Cutaneous dissemination may be an indicator of widespread
      metastasis to internal organs and is consistently fatal.

PMID- 11952704
TI  - Cutaneous metastases from Ewing's sarcoma: report of two cases.
AB  - Ewing's sarcoma is a malignant osseous neoplasm that affects mostly children and
      young adult males. Clinically, the neoplasm presents with oedema, swelling, and
      pain of the involved area. Histopathologically, Ewing's sarcoma consists of solid
      sheets of small round cells, with vesicular nuclei and scant cytoplasm, arranged
      in irregular masses separated by strands of fibrous tissue, with areas of
      necrosis en masse intermingled with intratumoural haemorrhage. Ewing's sarcoma is
      an extremely aggressive neoplasm and metastases to sites such as lung, pleura,
      other bones, central nervous system, liver, and regional lymph nodes frequently
      develop in early stages of the disease. Surprisingly, despite the highly
      aggressive biological behaviour of this neoplasm, cutaneous metastases from
      Ewing's sarcoma are very uncommon. We report two patients with Ewing's sarcoma of
      the bone who developed cutaneous metastases. As in other internal malignancies,
      the onset of cutaneous metastases in patients with Ewing's sarcoma indicates a
      poor prognosis.

PMID- 11952705
TI  - Lip reduction cheiloplasty for Miescher's granulomatous macrocheilitis (Cheilitis
      granulomatosa) in childhood.
AB  - Miescher's granulomatous macrocheilitis (cheilitis granulomatosa) is a mono-
      symptomatic presentation of Melkersson-Rosenthal Syndrome which is characterized
      by granulomatous swelling of the lips, and can affect both children and adults.
      We report the successful outcome following lip reduction surgery on an 11-year
      old boy. We suggest that surgery may have a role in the management of those
      patients who have failed to respond to medical treatment.

PMID- 11952706
TI  - Drug eruption secondary to aciclovir with recall phenomenon in a dermatome
      previously affected by herpes zoster.
AB  - Classically, recall dermatitis refers to chemotherapy-induced reactivation of
      skin damage caused by radiotherapy months, or even years, earlier. The concept of
      recall dermatitis has now been extended to include radiation recall dermatitis
      induced by other drugs, ultraviolet radiation, extravasation of drugs, and
      allergic contact dermatitis. We now describe recall dermatitis along the residual
      cutaneous lesions of a previous thoracic herpes zoster in a patient who developed
      a drug eruption after oral administration of aciclovir. The most striking feature
      consisted of confluent linear erythema along the dermatomes previously involved
      by the herpes zoster episode. Histopathologic study demonstrated small foci of
      spongiosis, vacuolar changes involving the basal layer of the epidermis and
      single necrotic keratinocytes scattered within the epidermis. The papillary
      dermis appeared oedematous and with dilated blood capillaries surrounded by a
      sparse inflammatory infiltrate composed mainly of lymphocytes. Serial sections
      failed to demonstrate cytologic changes of herpes varicella zoster infection. We
      interpreted this case as an example of recall dermatitis because the widespread
      cutaneous eruption secondary to aciclovir was more intense in skin previously
      compromised by herpes varicella zoster infection. To the best of our knowledge,
      recall dermatitis has not been described before at the site of previous
      involvement by herpes zoster.

PMID- 11952708
TI  - Irritant dermatitis, irritancy and its role in allergic contact dermatitis.
AB  - Irritant contact dermatitis is the clinical result of sufficient inflammation
      arising from release of pro-inflammatory cytokines from skin cells (principally
      keratinocytes) in response to (usually) chemical stimuli. Different clinical
      forms may arise. The three main pathophysiological changes seen are skin barrier
      disruption, epidermal cellular changes and cytokine release. An important role of
      irritancy in allergic contact dermatitis (ACD) comes from earlier animal and
      human studies. Evidence is outlined which is consistent with a "danger model" of
      ACD rather than one based on a traditional "self-nonself" immune model. In such a
      model an antigenic signal will produce sensitization only in the presence of a
      danger signal; in the absence of a danger signal tolerance will occur. We propose
      that the danger signal in ACD is cytokine release from nonimmune skin cells
      (principally keratinocytes) and that both the antigenic and "danger" signals
      arises from the hapten.

PMID- 11952707
TI  - Widespread skin-limited adult Langerhans cell histiocytosis: long-term follow-up
      with good response to interferon alpha.
AB  - Langerhans cell histiocytosis (LCH) most frequently involves bone, but also
      involves the skin in 40% of cases; in 10% of patients it is limited to the skin.
      Cutaneous findings of skin-limited LCH are scaly papules, vesicles, nodules,
      tumours with erosion, ulceration, or crusting and/or purpura. We report a case of
      widespread adult-onset LCH confined to skin in which topical carmustine,
      photochemotherapy, systemic steroids, and 2-chlorodeoxyadenosine were only
      partially effective. However, longer remission was achieved by the use of
      subcutaneous interferon-alpha2b.

PMID- 11952709
TI  - Evaluation of skin surface hydration in Korean psoriasis patients: a possible
      factor influencing psoriasis.
AB  - Psoriasis is recognized as a chronic, relapsing disorder of the skin, and its
      clinical course is influenced by various environmental factors. However, only a
      few articles have addressed the effect of low epidermal hydration status as an
      exacerbating factor of psoriasis. Our study was performed to investigate the
      relationship between subjective assessment and quantified data regarding dryness
      parameters in psoriasis patients. Seventy psoriasis patients were enrolled in our
      study. Subjective assessments were undertaken by evaluating the extent of
      involvement, erythema, scale and infiltration of individual lesions. Functional
      status of stratum corneum was evaluated by measuring electrical capacitance and
      conductance of the lesional and uninvolved skin of psoriatic patients. In
      addition, measurement of trans-epidermal water loss was performed. The results
      showed poor hydration status and barrier function in involved psoriatic epidermis
      compared with the uninvolved skin. Subjective assessment showed fairly good
      correlation with the quantified values. In conclusion, the degree of dryness in
      psoriatic skin lesions--which we presume to be one of the aggravating factors of
      psoriasis--seemed to be related to disease severity.

PMID- 11952710
TI  - Expression of endoglin in human melanocytic lesions.
AB  - Angiogenesis plays an important role in progression of various tumours including
      malignant melanoma. It is possible that the immunostaining of angiogenic markers
      could differentiate benign and malignant melanocytic lesions or that the
      immunostaining pattern with angiogenic markers could vary with tumour thickness
      and thus be a prognostic marker. We were interested to see whether there was any
      correlation between endoglin (CD 105; EDG) expression with tumour thickness in
      primary cutaneous malignant melanomas (MM), any correlation between EDG
      expression and clinical outcome in patients with primary cutaneous MMs and any
      difference in staining pattern between cutaneous MMs and Spitz naevi which could
      be of diagnostic value. Tissue sections from 14 primary cutaneous MM lesions with
      a Breslow thickness of > 2 mm, 10 primary cutaneous MM lesions with a Breslow
      thickness of 1-2 mm, and six Spitz and 10 compound naevi were stained for EDG.
      EDG expression was compared with survival in patients with primary cutaneous MMs.
      Overall, EDG staining was positive in 96% of MMs and 94% of benign melanocytic
      naevi. Very strong (++++) and strong (+++) EDG staining was found in 58% of MMs
      and 56% of benign melanocytic lesions. EDG expression did not vary significantly
      with the thickness of the lesion in primary cutaneous melanoma. Survival of
      melanoma patients did not correlate with the degree of EDG expression. Therefore,
      expression of this marker alone is not sufficient to differentiate benign and
      malignant melanocytic lesions.

PMID- 11952711
TI  - Diagnosis of Werner syndrome by immunoblot analysis.
AB  - Werner syndrome (WS) is caused by mutations in the gene encoding RecQ type DNA
      helicase (WRN). We report a 53-year-old Japanese male with WS who initially
      presented with skin ulcers on the feet and the left elbow. The patient had a high
      pitched voice, hoarseness, a characteristic bird-like facial appearance with a
      beak-shaped nose, canities and juvenile cataracts. Immunoblot analysis using a
      monoclonal antibody directed against the WS gene product DNA helicase revealed
      that the patient's leucocytes lacked this particular molecule, confirming the
      diagnosis of WS. This new immunoblot system therefore enables the diagnosis of WS
      to be made without the need to undertake more complex mutational analysis.

PMID- 11952712
TI  - Treatment of Grover's disease with tacalcitol.

PMID- 11952714
TI  - Spontaneous resolution of chronic actinic dermatitis in a young patient with
      atopic dermatitis.

PMID- 11952713
TI  - Flegel's disease: treatment with topical calcipotriol.

PMID- 11952715
TI  - Two-week skin cancer referrals.

PMID- 11952717
TI  - Viridans group streptococci: a reservoir of resistant bacteria in oral cavities.
AB  - The worldwide spread of erythromycin A-resistant streptococci, including
      Streptococcus pneumoniae, is of concern. Many studies have demonstrated that the
      viridans group streptococci can be a reservoir of erythromycin A resistance.
      Within oral streptoccoci, an important difference in the susceptibility pattern
      has been noted. The purpose of this short editorial is to highlight the
      importance of this group of bacteria as a reservoir of resistance to erythromycin
      A and the possible transfer of resistance to S. pneumoniae and S. pyogenes.

PMID- 11952716
TI  - Repeated PUVA treatment of aquagenic pruritus.

PMID- 11952718
TI  - Procalcitonin and other markers of infection. What should be their role in
      clinical practice?
AB  - Clinicians are always faced with a decision when confronted with a febrile
      patient; they must decide between what is an infectious condition and what is
      not, and between what merits hospital observation, what requires empirical
      antibiotic treatment and what needs outpatient follow-up. In this respect,
      judgement based on medical history and physical examination outweigh the
      predictive value of various laboratory markers of infection, as the latter
      generally reflect a nonspecific reaction of the host to widely different
      infectious and inflammatory stimuli. In the evaluation of specific subgroups of
      patients, e.g. those in the intensive care unit, laboratory tests should also
      preferably form a continuum with medical history and physical examination, aimed
      at clarifying host condition, the setting and the source of a possible infection.

PMID- 11952719
TI  - Present treatment expectations and risks of chronic hepatitis C.
AB  - During recent years, the treatment of chronic hepatitis C has increased in
      efficacy. Initially, the only approved treatment for this disease was interferon
      alpha (IFN-alpha) monotherapy, achieving a 15% rate of sustained response.
      Subsequently, a combination of IFN-alpha plus ribavirin showed a greater
      efficacy: up to 40% success with 3 MU of IFN-alpha three times weekly and 1000
      1200 mg of ribavirin daily in naive patients and in those who had relapsed after
      a course of IFN-alpha therapy. Pegylated interferon (PEG-IFN), due to its better
      efficacy and tolerance, has displaced the use of recombinant IFN. Nevertheless,
      the sustained response rate mainly depends on HCV RNA load and HCV genotype.
      Presumably, in future, new strategies based on gene therapy will play an
      important role in the treatment of chronic hepatitis C.

PMID- 11952720
TI  - Hepatitis C in HIV-infected patients--therapeutic approach.
AB  - The use of highly active antiretroviral therapy (HAART) has extended the lifespan
      of patients infected with human immunodeficiency virus (HIV). As the prognosis of
      HIV infection has improved, liver disease associated with hepatitis C virus (HCV)
      has become clinically significant in patients with HIV, liver failure being a
      frequent cause of death in this population. HIV infection may accelerate the
      course of liver disease in patients co-infected with HCV, so infection with HCV
      should be treated like any other opportunistic disease in these patients.
      Nowadays, combination therapy with interferon-alpha and ribavirin is the standard
      treatment for chronic hepatitis C in HIV-negative patients. Preliminary results
      of combination therapy in HIV/HCV co-infected patients have been promising,
      showing a sustained response rate in 40% of these patients. Patients with higher
      CD4 counts and lower HCV/HIV viral load and those infected with HCV genotype 3a
      have a better response to therapy. Potential drug interactions between HAART
      therapy and interferon and ribavirin treatment emphasize the importance of
      initiating treatment of HCV infection in HIV-positive individuals as soon as
      possible and ideally before the need for anti-HIV therapy. Recent case reports
      have suggested that liver transplantation might be an appropriate procedure in
      HIV patients with undetectable HIV viral load, high CD4 counts and HCV advanced
      liver disease. However, the limited amount of available information and the
      complexities of drug interactions between HAART therapy and immunosuppressive
      drugs oblige us to be prudent within considering such a procedure.

PMID- 11952721
TI  - Erythromycin susceptibility of viridans streptococci from the normal throat flora
      of patients treated with azithromycin or clarithromycin.
AB  - OBJECTIVE: To study the emergence of macrolide resistance in throat flora
      following treatment with clarithromycin or azithromycin. METHODS: Throat samples
      were collected before and after treatment and plated as a lawn on Columbia blood
      agar with an erythromycin E test strip. Minimum inhibitory concentrations (MICs)
      of erythromycin, clarithromycin and azithromycin were determined against isolates
      of distinct morphology with erythromycin E test MIC results equal to or greater
      than 2 mg/L. Polymerase chain reaction techniques were used to determine the
      genetic mechanisms of resistance. RESULTS: There were 749 resistant isolates of
      which 474 (63%) were streptococci. Only a quarter of the patients had no
      resistant streptococci before treatment started. There were increases in the
      numbers of resistant isolates and in the number of patients carrying a resistant
      flora during and after treatment. The most common genes identified were mefA/E in
      isolates with low-level resistance and ermA/M in isolates with high-level
      resistance. CONCLUSIONS: There is a pool of streptococci carrying genes
      associated with macrolide resistance in the normal respiratory flora of generally
      healthy adults. Differences between the patients treated with clarithromycin and
      those treated with azithromycin were difficult to assess because of the large
      number of patients in each group with macrolide-resistant streptococci before
      treatment. Although there were some differences these were not statistically
      significant.

PMID- 11952722
TI  - Procalcitonin, C-reactive protein and APACHE II score for risk evaluation in
      patients with severe pneumonia.
AB  - OBJECTIVE: Procalcitonin (PCT) is a peptide that is found elevated in patients
      with sepsis and severe infections. In healthy persons PCT serum levels are below
      0.1 ng/mL. The aim of this study was to investigate the value of serum PCT
      determination for risk evaluation in patients with pneumonia. METHODS: We focused
      on the correlation of PCT with the clinical status of the patient and prognosis
      of the disease. In a prospective study, in a nonsurgical intensive care unit the
      following parameters were assessed regularly in 93 patients with documented
      pneumonia: C-reactive protein (CRP), white blood cell count (WBC), body
      temperature, PCT and Acute Physiology and Chronic Health Evaluation (APACHE) II
      score. RESULTS: At the onset of infection 50% of the patients had elevated PCT
      levels above 2 ng/mL. The model of multivariate analysis of all tested parameters
      on days 0-5 stratified for clinical outcome (change in clinical classification or
      death) showed local significance for APACHE II score only. None of the other
      parameters in this model serves as an isolated indicator for change of clinical
      status or death. An intra-individual change of body temperature or CRP was never
      significantly associated with a change in the clinical status of the patient.
      CONCLUSION: Change in PCT on admission and at the end of the observation period
      significantly indicated a clinical change.

PMID- 11952723
TI  - Proficiency of Italian clinical laboratories in detecting reduced glycopeptide
      susceptibility in Enterococcus and Staphylococcus spp. using routine laboratory
      methodologies.
AB  - OBJECTIVE: To assess the ability of 59 clinical microbiology laboratories
      distributed throughout Italy to correctly identify and detect reduced
      susceptibility to glycopeptides in staphylococci and VanA-, VanB- or VanC
      mediated glycopeptide resistance in enterococci. METHODS: Eight test strains
      comprising three staphylococci (S. aureus ATCC 29212 and two vancomycin
      intermediate S. haemolyticus [11105301, 10030683Y]) and five enterococci (E.
      faecalis ATCC 29212, E. faecalis ATCC 51299 VanB, E. faecium AIB40 VanA, E.
      faecalis V583 VanB and E. gallinarum AIB39 VanC1) were distributed to 59 Italian
      clinical microbiology laboratories. Each isolate was blind-coded, and
      laboratories were instructed to identify the strains and test isolates for
      susceptibility to teicoplanin and vancomycin using their standard methods.
      Results were assessed against consensus test results obtained by a reference
      laboratory. In addition, to complement data interpretation, laboratories were
      asked to provide retrospective routine test results from their respective
      hospitals. RESULTS: All 59 laboratories participating in the study completed the
      susceptibility testing and provided data for analysis. A total of 53 laboratories
      provided retrospective routine data. Overall, laboratories were able to identify
      isolates to the genus level successfully. E. gallinarum and S. haemolyticus posed
      problems for species identification, with only 40.6 and 71.2%, respectively, of
      results reported correctly; most incorrect results were reported as 'other
      species'. For enterococcal test strains, VanA phenotypes were detected correctly
      by 96.6% of laboratories; VanB by 30.5% (E. faecalis ATCC 51299) and 88.1% (E.
      faecalis V583); and VanC1 by 67.8%. For staphylococcal test strains, 28.8% (S.
      haemolyticus 11105301) and 23.7% (S. haemolyticus 10030683Y) of the laboratories
      were able to detect reduced susceptibility to vancomycin. Errors in detecting
      vancomycin resistance in VanB and VanC1 enterococci were made with all methods,
      most noticeably by disk diffusion users. For staphylococci, most errors in
      reporting vancomycin-intermediate resistance occurred with disk diffusion and
      Vitek (software version 5.04) users. Overall, considerably fewer errors occurred
      with the detection of teicoplanin resistance, especially for staphylococci. For
      1999, routine results show that 41/1749 (2.4%) of E. faecium, 220/11 180 (2.0%)
      of E. faecalis, 29/24 927 (0.12%) of S. aureus and 54/22 102 (0.24%) of coagulase
      negative staphylococci were reported as resistant to vancomycin. CONCLUSION:
      Italian laboratories are able to identify staphylococci and enterococci
      adequately, although all methodologies used have problems in identifying E.
      gallinarum and coagulase-negative staphylococci to the species level. While VanA
      phenotypes were efficiently detected, problems were experienced in detecting VanB
      and VanC phenotypes. The majority of laboratories were unable to detect reduced
      vancomycin susceptibility in staphylococci adequately, especially with disk
      diffusion and older Vitek systems. Teicoplanin appeared useful as a marker for
      detecting vancomycin resistance, particularly with disk diffusion. Should
      enterococcal VanB or staphylococcal glycopeptide-intermediate phenotypes become
      prevalent in Italy, it is likely that they would be under-detected. New systems
      under development, such as Vitek2, should improve this situation.

PMID- 11952725
TI  - Clinically and histologically silent Q fever endocarditis accidentally diagnosed
      by PCR.
AB  - A case of Q fever endocarditis was diagnosed in a patient with no sign of active
      endocarditis by performing PCR targeting eubacterial 16S rDNA on the resected
      mitral valve. The diagnosis was confirmed by detection of high levels of anti
      Coxiella burnetti antibodies, positive immunohistologic analysis of the valve
      tissue with specific antibodies and culture of C. burnetti from the valve tissue.
      As this patient had an unexplained aggravation of valve dysfunction, we
      recommended routine serologic testing for C. burnetti to allow the diagnosis of Q
      fever endocarditis at a very early stage.

PMID- 11952724
TI  - Clinical microbiological case: right lower abdominal pain progressing to acute
      abdomen.

PMID- 11952726
TI  - Systemic lupus erythematosus associated with acute parvovirus B19 infection.
AB  - Acute parvovirus B19 infection has been implicated in the pathogenesis of several
      autoimmune conditions, including systemic lupus erythematosus. Viruses, including
      human parvovirus B19, may trigger bouts of systemic lupus erythematosus in
      genetically susceptible individuals. Herein, we report on two patients who
      developed systemic lupus erythematosus associated with acute parvovirus B19
      infection and discuss the possible pathogenetic mechanisms implicated.

PMID- 11952728
TI  - Mecillinam susceptibility as an indicator of beta-lactamase production in
      Staphylococcus aureus.
AB  - The use of direct susceptibility testing from specimens has led to the fortuitous
      observation that penicillin-susceptible strains have larger inhibition zones for
      mecillinam than do beta-lactamase producers. The current study was, therefore,
      undertaken to test 179 Staphylococcus aureus isolates for mecillinam
      susceptibility by Rosco Neo-Sensitabs and to compare the results with commonly
      used tests for beta-lactamase production, i.e. size and character of penicillin
      inhibition zones, chromogenic cephalosporin (nitrocefin) tests and clover leaf
      assays. Agreement between methods was reached for 175 of 179 strains when
      disregarding the results of the nitrocefin tests, 88 isolates being found
      susceptible and 87 being found to be beta-lactamase producers. All 88 susceptible
      isolates had mecillinam zones of >22 mm, with the great majority being >25 mm;
      double zones did, however, occur. The 87 beta-lactamase producers had zones <14
      mm or no zones. Four isolates presenting problems in had mecillinam zones of
      <or=20 mm and were without tapering growth at the penicillin inhibition zone
      edge. In conclusion, the size of the mecillinam inhibition zone is found to be a
      useful supplementary test in the clinically important distinction between beta
      lactamase-producing and non-producing isolates of S. aureus.

PMID- 11952727
TI  - Feasibility of introducing rejection criteria for stool cultures in a teaching
      hospital in Portugal.
AB  - The possible introduction of rejection criteria for stool cultures (<or= 3 days
      hospitalization and <or= 2 specimens) were investigated in a teaching hospital in
      Portugal. During 12 months, 854 specimens from 537 patients (37% of them adults)
      were observed. Sixteen percent of inpatients had a positive stool culture (adults
      9.7%, pediatric 21.7%). Eighty-five percent had <or= 3 days of hospitalization.
      Application of the '3-day-rule' would have led to 12 missed cases. Only in three
      cases would previously proposed exceptions to the rejection criteria have
      applied. A '5-day-rule' and <or= 2 specimen/patients seem to be more suitable,
      based on the different hospital conditions present here.

PMID- 11952729
TI  - Mycobacterium fortuitum complex endocarditis-case report and literature review.
AB  - Endocarditis due to Mycobacterium fortuitum complex is a rare entity generally
      linked to the hospital environment. Only 18 cases have been published since 1966.
      Here we present a case of a female who developed an endocarditis due to
      Mycobacterium chelonae after valve replacement as well as a review of the
      literature. The course of this kind of endocarditis is generally subacute and the
      outcome is usually fatal. Blood cultures were positive in 75% of cases of
      metallic valve endocarditis, versus 20% in bioprostheses. The treatment must
      include antibiotics that have shown activity against these mycobacteria, such as
      amikacin, imipenem, cefoxitin, fluorinated quinolones and macrolides (especially
      clarithromycin). Surgical removal is recommended. Although the prognosis for the
      patient is poor, we should expect better outcomes with the use of new antibiotic
      regimens.

PMID- 11952731
TI  - Probing around implants and teeth with healthy or inflamed peri-implant
      mucosa/gingiva. A histologic comparison in cynomolgus monkeys (Macaca
      fascicularis).
AB  - The purpose of this study was to obtain a better understanding of probing
      measurements around osseointegrated oral implants. A comparison was made of probe
      tip position around Astra Tech implants and teeth of eight cynomolgus monkeys
      (Macaca fascicularis) in conditions of i) healthy peri-implant mucosa/gingiva,
      ii) mild mucositis/gingivitis, iii) severe mucositis/gingivitis or iv) peri
      implantitis/periodontitis. Histological sections of 128 probes that were attached
      to implants or teeth with surrounding tissues were prepared by the cutting
      grinding technique. No systematic differences were identified in the clinical and
      histological estimates of the distance between the mucosal/gingival margin and
      the probe tip. The differences were mainly smaller than 0.5 mm, and in no case
      were they larger than 0.7 mm. For implants and teeth with healthy peri-implant
      mucosa/gingiva, the distance between the probe tip and the alveolar bone was
      similar and ranged from 0.5 to 1.5 mm (P = 0.97). However, the probe tip was
      closer to bone around implants than around teeth in conditions of mild
      mucositis/gingivitis (P = 0.034), severe mucositis/gingivitis (P < or = 0.0001)
      and peri-implantitis/periodontitis (P < or = 0.0001). Around implants with severe
      mucositis and peri-implantitis, the distance was generally smaller than 0.5 mm,
      whereas teeth with severe gingivitis and periodontitis showed distances that
      mainly ranged from 0.5 to 1.5 mm. In conclusion, the probing measurements around
      osseointegrated oral implants and teeth were different. Even mild marginal
      inflammation was associated with deeper probe penetration around implants in
      comparison to teeth.

PMID- 11952732
TI  - Long-term follow-up of osseointegrated titanium implants using clinical,
      radiographic and microbiological parameters.
AB  - The aim of this study was to longitudinally follow up osseointegrated titanium
      implants in partially dentate patients by clinical, radiographic and
      microbiological parameters in order to evaluate possible changes in the peri
      implant health over time. Fifteen individuals treated with titanium implants, ad
      modum Branemark, and followed for ten years were included in the study. Before
      implant placement ten years previously, the individuals had been treated for
      advanced periodontal disease and thereafter been included in a maintenance care
      program. The survival rate of the implants after ten years was 94.7%. The bone
      loss was 1.7 mm when using the abutment-fixture junction as a reference point. Of
      the individuals, 50% were positive for plaque at the implants. Bleeding on sulcus
      probing was present at 61% of the implant surfaces. Ten years previously, the
      individuals had been carriers of putative periodontal pathogens, such as
      Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus
      actinomycetemcomitans, Capnocytophaga spp. and Campylobacter rectus, and were
      also carriers of these species at the current examination. The results of the
      present study suggest that the presence of these putative periodontal pathogens
      at implants may not be associated with an impaired implant treatment. These
      species are most likely part of the normal resident microbiota of most
      individuals and may therefore be found at random at both stable and progressing
      peri-implant sites.

PMID- 11952733
TI  - Long-term clinical effectiveness of oral implants in the treatment of partial
      edentulism. Seven-year life table analysis of a prospective study with ITI dental
      implants system used for single-tooth restorations.
AB  - One hundred and eight-seven ITI implants were prospectively followed from
      November 1992 to July 2000, in order to evaluate the clinical efficiency and the
      long-term prognosis in 109 partially edentulous patients (69 women and 40 men;
      average age 41.3 years). Of these 187 implants, 69.5% were placed in the mandible
      and 30.5% in the maxilla. After a healing period that ranged from three to six
      months, the osseointegrated implants (n = 184) were restored with single crowns.
      Three implants were extracted prior to loading the fixture and were considered
      early failures. Each implant was reassessed on a yearly basis, both clinically
      and radiographically. The results of the investigation, which were evaluated
      according to predefined success criteria, were reviewed in accordance with a life
      table method. During the follow-up, six cases were deemed to be late failures. In
      each of these cases, a suppurative infection of the peri-implant tissue was
      diagnosed: in one implant, the infection could not be eradicated and the implant
      was removed. When 11 drop-outs were included in the analysis, the cumulative
      survival and success rates for the whole sample group were 96.77% and 93.6%,
      respectively. When only prosthetically loaded implants were considered, the
      results increased to 99.35% for the cumulative survival rate and 96.18% for the
      cumulative success rate. The analysis on disaggregated data showed better results
      for maxillary restorations (survival rate 100%) in comparison to mandible
      restorations (survival rate 95.11%). It was concluded that, under standard
      anatomic conditions (bone site height > 8 mm, thickness > 6 mm), prosthetic
      restoration of partially edentulous patients with the ITI system can be described
      as a reliable and efficient therapy in the long term.

PMID- 11952734
TI  - The use of reduced healing times on ITI implants with a sandblasted and acid
      etched (SLA) surface: early results from clinical trials on ITI SLA implants.
AB  - ITI dental implants are available with two bone-anchoring surfaces, a titanium
      plasma-sprayed (TPS) surface, and a recently introduced sandblasted and acid
      etched (SLA) surface. Cell culture and animal tests demonstrate that the SLA
      surface stimulates bone cell differentiation and protein production, has large
      amounts of bone-to-implant contact, and results in large removal torque values in
      functional testing of the bone contact. As a result of these studies, a
      prospective human clinical trial was initiated to determine whether the 4.1 mm
      diameter SLA ITI solid screw implants could be predictably and safely restored as
      early as six weeks after implant placement surgery. The protocol restricted the
      use of the reduced healing time to a) healthy patients with sufficient bone
      volume to surround the implant, and b) those patients who had good bone quality
      (classes I-III) at the implant recipient site. Patients with poorer bone quality
      (class IV) did not have restorations until 12 weeks after implant placement. The
      clinical trial is an ongoing multicenter trial, with six centers in four
      countries, and with follow-up over five years. The primary outcome variable was
      abutment placement with a 35 Ncm force, with no countertorque and no pain or
      rotation of the implant. A secondary outcome was implant success, as defined by
      no mobility, no persistent pain or infection, and no peri-implant radiolucency.
      To date, 110 patients with 326 implants have completed the one-year post-loading
      recall visit, while 47 patients with 138 implants have completed the two-year
      recall. Three implants were lost prior to abutment connection. Prosthetic
      restoration was commenced after shortened healing times on 307 implants. The
      success rate for these implants, as judged by abutment placement, was 99.3% (with
      an average healing time of 49 days). Life table analyses demonstrated an implant
      success rate of 99.1%, both for 329 implants at one year and for 138 implants at
      two years. In the 24-month period after restoration, no implant losses were
      reported for the 138 implants. These results demonstrate that, under defined
      conditions, solid screw ITI implants with an SLA endosseous surface can be
      restored after approximately six weeks of healing with a high predictability of
      success, defined by abutment placement at 35 Ncm without countertorque, and with
      subsequent implant success rates of greater than 99% two years after restoration.

PMID- 11952735
TI  - A multicenter prospective evaluation of 2-months loaded Osseotite implants placed
      in the posterior jaws: 3-year follow-up results.
AB  - In this prospective study, the clinical outcome of 2-months loaded implants
      placed in the posterior jaws was evaluated after up to 3 years of functional
      loading. 405 Osseotite implants with microtextured acid-etched surface were
      consecutively placed in 11 fully and 164 partially edentulous patients (mean age
      53.5 +/- 15.3 (S.D.) years) using a one-stage technique. 282 implants, supporting
      154 restorations, were placed in the mandible, while 123 implants, supporting 75
      restorations, were placed in the maxilla. A total of 99 single-tooth
      restorations, 119 short-span fixed bridges and 11 full-arch prostheses were
      applied. The mean time interval from surgery to connection of provisional
      restoration was 2.0 +/- 0.7 months. 9 failures were reported up to 3 years of
      follow-up; of these, 4 mandibular and 2 maxillary implants failed during the
      initial healing period (before prosthesis connection), while 3 mandibular
      implants failed after loading. No other complications occurred throughout the
      study. Life table analysis showed a cumulative survival rate of 97.5% for the
      mandible and 98.4% for the maxilla. Post-loading implant survival rate was 98.9%
      for the mandible and 100% for the maxilla. The excellent outcome of this interim
      report suggests that microtextured Osseotite implants in the posterior jaws may
      safely bear a functional load applied 2 months after insertion. The results of
      the present study are particularly encouraging for implants placed in the
      maxilla, since both a significant reduction of the healing period compared to the
      6 months suggested by the classical Branemark protocol, and an excellent post
      loading function may be achieved also in low quality bone.

PMID- 11952736
TI  - Bone level changes proximal to oral implants supporting fixed partial prostheses.
AB  - The success of oral implant treatment relies on the presence and maintenance of
      bone adjacent to implants. The monitoring of radiographic bone level changes
      provides valuable insight into the longevity of oral implants. The purpose of
      this study was to measure radiographic bone level changes proximal (mesial and
      distal) to Branemark System) implants (Nobel Biocare AB, Goteborg, Sweden)
      supporting fixed partial prostheses. Measurements were used to determine mean
      bone loss for the first year of loading by the prosthesis and the mean annual
      bone loss for subsequent years. These results were then compared and contrasted
      with various characteristics of the individuals, treatment, and treatment
      outcomes. Fifty-five subjects with 69 fixed partial prostheses supported by 160
      implants were followed over a 1 to 12-year period. A mean bone loss of 0.33 mm
      (SD 0.59) was measured for the first year of loading and a mean annual bone loss
      of 0.00 mm (SD 0.11) after the first year. The radiographic bone loss calculated
      for implants at the first year of loading was positively correlated with the mean
      annual bone loss thereafter. Males, younger individuals and those implants
      supporting distal extension prostheses lost significantly more bone in the first
      year of loading. Larger numbers of implants followed for longer periods of time
      are needed to further explore the effects of various aspects of treatment on bone
      loss.

PMID- 11952738
TI  - Augmentation of the mandible with GTR and onlay cortical bone grafting. An
      experimental study in the rat.
AB  - The aim of the present study was to evaluate the effect of augmenting the
      mandible with onlay mandibular bone grafts that were covered with e-PTFE
      membranes according to the principle of guided tissue regeneration (GTR). The
      experiment was carried out in 30 rats. The inferior border of the mandible and
      parts of the mandibular body were exposed on both sides. On one side, an
      autogenous bone graft that was harvested from the angle of the mandible was
      placed on the inferior border of the mandible and was fixed with a titanium
      microimplant. Subsequently, the graft was covered with an e-PTFE membrane. The
      contralateral side, serving as control, was treated the same way except for the
      placement of the membrane. Groups of six animals were sacrificed 15, 30, 60, 120
      and 180 days following surgery, and specimens that were prepared from the
      experimental and control sites were analyzed histologically. The bone graft
      underneath the membrane initially presented superficial resorption but,
      subsequently, the space that was created by the membrane gradually became filled
      with bone. After 180 days, the area underneath the membrane was completely filled
      with bone and it was impossible to distinguish between the bone graft and the
      newly formed bone. Generally, the bone grafts at the control sides were
      characterized by a gradual resorption during the entire experimental period. At
      180 days after transplantation, only a few grafts at the control sites had
      retained their height, and there was frequently a lack of continuity between the
      bone graft and the underlying mandibular bone. It can be concluded that onlay
      mandibular bone grafts combined with GTR may improve the predictability of
      mandibular augmentation, in comparison to bone grafting alone.

PMID- 11952737
TI  - The effects of fixed and removable implant-stabilised prostheses on posterior
      mandibular residual ridge resorption.
AB  - This study investigated the change over time in the area of the posterior
      mandibular residual ridge in patients wearing either i) mandibular overdentures
      stabilised by two implants (Branemark System; Nobel Biocare, Goteborg, Sweden)
      connected by a bar, or ii) mandibular fixed cantilever prostheses stabilised on
      five or six implants. Proportional measurements were made in order to compare the
      area of the residual ridge with an area of bone uninfluenced by resorption.
      Measurements were made by digitising tracings of panoramic radiographs that were
      taken shortly after implant insertion and up to seven years later. With the use
      of overdentures, the posterior bone area index reduced by a mean of 1.1% per
      annum, while a mean bone area index increase of 1.6% per annum was demonstrated
      in association with fixed prostheses. A multiple linear regression model was
      fitted to predict the change in posterior area from type of prosthesis, gender,
      age, years of edentulism and initial height of the mandible. The model was only
      significant for initial height of mandible (P = 0.04) and type of prosthesis (P =
      0.0001). In conclusion, patients rehabilitated with implant-stabilised mandibular
      overdentures demonstrated low rates of posterior mandibular residual ridge
      resorption, while patients rehabilitated with implant-stabilised mandibular fixed
      cantilever prostheses demonstrated bone apposition in the same area.

PMID- 11952739
TI  - Alveolar ridge augmentation by combining autogenous mandibular bone grafts and
      non-resorbable membranes.
AB  - The aim of the present study was to evaluate the effect of using mandibular
      cortical bone grafts covered with e-PTFE membranes for maxillary alveolar ridge
      augmentation, in comparison with the use of mandibular cortical grafts alone. The
      experiment was carried out in 20 rats. At one side of the maxillary jaw, the
      edentulous alveolar ridge between the incisor and the first molar was augmented
      by means of an autogenous mandibular bone graft, which was fixed with a titanium
      microimplant and covered with a Teflon membrane. The contralateral side, serving
      as control, was treated the same way, except for the placement of a membrane.
      Histological analysis at 15, 30, 60 and 90 days after surgery demonstrated that,
      in situations where the membrane was not exposed to the oral cavity during
      healing, the mandibular bone grafts presented no resorption and were in
      continuity with the maxillary bone at the recipient site. In situations where the
      membrane had become exposed, however, the bone grafts presented extensive
      resorption and lack of continuity with the bone at the recipient site. These
      latter findings were similar to those made at the non-membrane-treated side. The
      results indicate that the volume of autogenous bone graft used for alveolar ridge
      augmentation can be retained by covering the graft with a membrane, provided that
      the membrane is properly adapted and is kept covered with mucosa during healing.

PMID- 11952740
TI  - Augmentation of the rat jaw with autogeneic cortico-cancellous bone grafts and
      guided tissue regeneration.
AB  - The aim of the present study was to evaluate the effect of augmenting the
      maxillary alveolar ridge and the lateral aspect of the mandible with onlay
      autogeneic cortico-cancellous bone grafts that were covered with e-PTFE
      membranes. The experiment was carried out in 51 rats. In 15 rats, the edentulous
      maxillary jaw between the incisor and the first molar was augmented by means of
      an autogeneic ischiac bone graft that was fixed with a gold-coated microimplant.
      In one side, the graft was covered with an e-PTFE membrane, while the other side,
      which served as control, was treated without a membrane. In the other 36 rats,
      the lateral aspect of the mandible was augmented in both sides by means of an
      autogeneic ischiac bone graft that was fixed with a gold-coated or a titanium
      microimplant. In one side, the augmented area was covered with an e-PTFE
      membrane, while the contralateral side was treated without a membrane.
      Histological analysis at 60, 120 and 180 days after augmentation of the maxilla
      showed that, in the case of the test sites (where most of the membranes were
      either exposed or lost), the bone grafts presented extensive resorption and there
      was a lack of bone continuity between the graft and the recipient site. Similar
      findings were made at the non-membrane-treated control sides. In the case of
      augmentation of the mandible with membranes, the bone grafts were not resorbed,
      but were integrated into newly formed bone at the recipient site. In the control
      sides, the grafts presented varying degrees of resorption and integration into
      the recipient bone. It is concluded that, in comparison to bone grafting alone,
      onlay ischiac bone grafting combined with guided tissue regeneration eliminates
      the risk of bone graft resorption and ensures integration of the graft into newly
      formed bone at the recipient site, provided that closure of the operated area can
      be maintained during healing.

PMID- 11952741
TI  - Alveolar ridge augmentation using a resorbable copolymer membrane and autogenous
      bone grafts. An experimental study in the rat.
AB  - The aim of the present study was to compare the result of maxillary alveolar
      ridge augmentation by the combined use of mandibular bone grafts and resorbable
      membranes (Resolut), with that achieved by the use of the same type of bone graft
      combined with the placement of e-PTFE membranes (Gore-Tex). The experiment was
      carried out in 30 rats. In one side of the maxillary jaw, the edentulous alveolar
      ridge between the incisor and the first molar was augmented by means of an
      autogenous mandibular bone graft that was fixed with a titanium microimplant and
      covered with a resorbable membrane. The contralateral side, serving as control,
      was treated in the same way, with the difference that an e-PTFE membrane was
      placed over the bone graft. Histological analysis at 15, 30, 60, 120 and 180 days
      after surgery demonstrated that, in both test and control sites where the
      membrane was properly adapted and not exposed, the bone grafts presented no
      resorption and were integrated into the maxillary bone at the recipient site. In
      cases where the membrane was exposed, however, the bone grafts presented
      extensive resorption and lack of continuity between the graft and the recipient
      bed. At 60-180 days after surgery, the exposure of both types of membrane had
      frequently led to complete resorption of the grafts, encapsulation of the
      titanium microimplant by fibrous connective tissue, or exfoliation of the
      microimplant. It is concluded that alveolar ridge augmentation can be predictably
      accomplished by combining mandibular bone grafting with the placement of
      resorbable or non-resorbable membranes according to the GTR principle, provided
      that the membrane is properly adapted over the graft and complete closure of the
      treated area is maintained during healing.

PMID- 11952742
TI  - Histomorphological evaluation of loaded plate-form and root-form implants in
      Macaca mulatta monkeys.
AB  - As part of a long-term evaluation of endosteal dental implants in primates, this
      paper describes the histological response to plate-form and root-form implants.
      Thirty-six primates received 48 mandibular distal abutment implants. After
      healing, the implants were restored with fixed partial dentures, which remained
      in function for two years. A subset of the group was ligated at the gingival
      sulcus to biologically stress tissues supporting the implants. Crestal bone
      height around implants was quantified using digital subtraction radiographic
      techniques. The ligated implants lost more crestal bone than non-ligated
      implants, as shown by ANOVA (P < 0.05). After retrieval, implants were embedded
      and sectioned for histomorphometric analysis including measurement of per cent
      osseointegration. Both plate-form and root-form non-ligated implants demonstrated
      about 60% osseointegration. When ligated, plate-form implants dropped to an
      average integration of only 34%, while root-form implants maintained 62%
      integration, a significant difference. These data show that in this primate
      model, plate-form and root-form implants maintained integration while in function
      for two years. When stressed with ligation, root-form implants maintained
      relative amounts of osseointegration, while per cent osseointegration of plate
      form implants decreased.

PMID- 11952743
TI  - Dynamics of bone marrow pressure with tapping of titanium and hydroxyapatite
      implants in rabbits.
AB  - The purpose of the present study was to evaluate the difference in stress
      transfer between titanium (Ti) and hydroxyapatite (HA) by the measurement of bone
      marrow pressure using a catheter pressure transducer. Ti and HA implants were
      inserted in the tibiae of rabbits. A hole of 1 mm in diameter was drilled in the
      bone and a fine catheter pressure transducer was placed in the bone marrow
      through a tube. The top of the abutment was vertically tapped with an impulse
      hammer, and the acceleration signal from the hammer and pressure signal from the
      catheter pressure transducer were examined. The time of contact (impulse
      duration) recorded in the impulse with Ti and HA was 166+/-17 micro sec and 164
      +/- 17 micro sec, respectively. Maximum bone marrow pressure (BMP) with Ti and HA
      was 54.2 +/- 32.6 and 47.5 +/- 10.0 mmHg, respectively. Variation of the BMP with
      Ti was significantly larger than that with HA (P < 0.05). A negative correlation
      coefficient between impulse duration and BMP was found. The results of the
      present study suggest that the stress transfer is different between Ti and HA
      implants using dynamics of the bone marrow pressure.

PMID- 11952744
TI  - Sture Rickard Nymann 1922-2002.

PMID- 11952745
TI  - Liquid-based cytology: is this the way forward for cervical screening?
AB  - Liquid-based cytology (LBC) is currently being marketed as an alternative
      methodology to replace the conventional PAP smear in cervical cytology. A
      substantial body of literature exists in support of LBC, some of which is at
      least partially sponsored by product manufacturers. The majority of published
      literature in support of LBC employs Bethesda reporting terminology. In this
      study we have analysed published raw data and presented this in NHSCSP
      terminology. Claims relating to sensitivity, specificity and smear adequacy have
      then been considered with reference to this data. Our analysis of existing data
      does not support the nationwide implementation of LBC at present. Further studies
      are recommended in order to evaluate the place of this technology within the
      NHSCSP.

PMID- 11952746
TI  - How predictive is a cervical smear suggesting glandular neoplasia?
AB  - The prevalence of endocervical adenocarcinoma and its precursors has increased,
      in part due to increased diagnostic awareness of these lesions. To date, limited
      information has been published regarding the predictive value of glandular
      abnormalities in cervical smears. This study details the histological follow up
      of 418 cervical smears showing glandular abnormality, reported in our department
      over a six year period from 1993 to 1998. Histological follow up was available
      for 395 of the 418 smears (94.50%). The overall positive predictive value (PPV)
      for this group of smears was 72.66% for either significant glandular or squamous
      pathology (at least low grade cervical glandular intraepithelial neoplasia or
      CIN2 on follow up biopsy), and 55.70% for significant glandular pathology alone.
      Examination of subcategories of abnormal glandular smear showed that the PPV
      increased with the degree of abnormality reported within the smears.

PMID- 11952747
TI  - Interlaboratory reproducibility of the immunocytochemical assessment of oestrogen
      and progesterone receptors and proliferative activity in fine needle aspiration
      of breast cancer.
AB  - The purpose of this study was to establish the interlaboratory reproducibility of
      immunocytochemical analysis of oestrogen (ER) and progesterone (PR) expression
      and Mib1 growth fraction on fine needle aspiration (FNA) smears. A set of 44
      immunostained slides for ER, PR and Mib1 were randomly selected from the archives
      of the Center for the Study and Prevention of Cancer (CSPO) of Florence, Italy,
      and submitted for reading to 6 Italian laboratories. The generalized kappa
      statistic was used as an indicator of agreement among the six laboratories. A
      good correlation for ER and PR was evident. For Mib1 the results showed some
      discrepancies. In addition to adequate standardization of procedures, these data
      confirm that the reliability of the immunocytochemistry is strictly linked to
      accurate analysis of the results.

PMID- 11952748
TI  - Fine needle aspiration cytology in the work-up of mammographic and
      ultrasonographic findings in breast cancer screening: an attempt at
      differentiating in situ and invasive carcinoma.
AB  - This study evaluated the results of fine needle aspiration cytology (FNAC) from
      the first four years of organized mammography screening for breast cancer in
      Oslo, particularly our policy in differentiating in situ and invasive carcinoma.
      Lesions were aspirated directly, ultrasound guided, by stereotaxic device or
      biopsy localization plate. All lesions were aspirated by cytopathologists working
      with the radiologists at the breast diagnostic centre. Smears were evaluated
      immediately for assessment of adequacy and a preliminary diagnosis was given to
      the surgeon. When FNAC revealed malignancy, diagnostic terms were as follows: (1)
      invasive carcinoma; (2) ductal carcinoma in situ of comedo type (high nuclear
      grade), cannot evaluate infiltration; (3) ductal carcinoma in situ of low nuclear
      grade and (4) papillary tumour, cannot evaluate infiltration. There were 953
      cases, 70% of which were nonpalpable. Insufficient material was obtained in 5.8%.
      Absolute and complete sensitivity were 81% and 91%, respectively. Specificity was
      85%. There were 448 histologically proven carcinomas. 383 of these were invasive.
      362 carcinomas (in situ and invasive) (80.8%) were diagnosed directly on FNAC.
      Distinction between invasive and in situ carcinoma was possible in 294 of 320
      directly diagnosed invasive carcinomas (91.8%). PPV of a diagnosis of invasive
      carcinoma was 97%. Our data showed that definitive cytological diagnosis of
      invasive carcinoma was possible in more than 90% of fully diagnostic smears and
      allowed definitive primary surgery in these women.

PMID- 11952749
TI  - Aspiration cytodiagnosis of the breast with abundant acellular calcific material
      indicative of soft tissue calcinosis (a study of 3 cases).
AB  - Calcific deposits in soft tissue are rare and may clinically resemble a tumour.
      It seems feasible, therefore, to investigate them by the non-invasive technique
      of fine needle aspiration cytology (FNAC). In this study three cases with
      extensive accumulation of acellular calcific material in the breast are described
      in which FNAC was indicative of soft tissue calcinosis. In all cases routine
      mammogram had shown a partially cystic opacity. All other investigations were
      normal and no significant family or medical history was present. Cytopreparations
      in all cases showed only abundant acellular calcium. The patients had no further
      treatment and on follow up were clinically well with no changes. The cases are
      interesting, since the cytohistological findings in the aspirate sample appeared
      to be strongly indicative of soft tissue calcinosis.

PMID- 11952750
TI  - Cytology of collagenous spherulosis of the breast: a diagnostic dilemma--report
      of three cases.
AB  - Collagenous spherulosis is a rare incidental finding seen in association with
      benign breast lesions. Cytological findings in three cases of collagenous
      spherulosis diagnosed on fine needle aspiration are presented. The presence of
      hyaline pink globules surrounded by benign myoepithelial cells in Giemsa stained
      smears was a diagnostic feature. Associated lesions were atypical papillary
      hyperplasia (2) and fibroadenoma (1). Adenoid cystic carcinoma was the close
      differential diagnosis on cytology. Awareness of this entity is important to
      avoid a false positive diagnosis of malignancy.

PMID- 11952751
TI  - Role of fine needle aspiration cytology in diagnosis of pleomorphic adenomas.
AB  - This retrospective study was carried out to review the cases diagnosed as
      pleomorphic adenoma in major or minor salivary glands and determine the
      difficulties encountered on typing this tumour on fine needle aspiration cytology
      (FNAC). Over a 19-year period (1982-2000) 488 pleomorphic adenomas were diagnosed
      on FNAC from different sites (parotid - 372 cases, submandibular - 95 cases; oral
      cavity - 21 cases). Histology was available in 232 cases. Twenty-nine cases where
      a histological diagnosis of pleomorphic adenoma was made but the cytological
      diagnosis was variable were also reviewed. In 216 of the 232 cases a good
      cytohistological correlation was available. On review only 4 of the 16 cases
      initially diagnosed as pleomorphic adenoma on FNAC where the histology revealed a
      different tumour were categorized as pleomorphic adenoma, while 3 each were
      classified as adenoid cystic carcinoma and benign tumour ?type, and 2 each were
      diagnosed to be muco-epidermoid carcinoma, monomorphic adenoma and acinic cell
      carcinoma. On review of the FNAC smears from 29 cases where a histological
      diagnosis of pleomorphic adenoma was available while the cytological diagnosis
      was variable, only 11 (38%) were categorized as pleomorphic adenoma. In the
      majority of the remaining cases the cytological diagnosis did not alter markedly,
      7 of 10 cases where the tumour could not be typed on cytology initially could not
      be typed even on review. In conclusion, FNAC is an ideal, fairly accurate
      preoperative procedure for the diagnosis of pleomorphic adenomas. Certain
      diagnostic problems occur in differentiating pleomorphic adenomas from adenoid
      cystic carcinoma, monomorphic adenoma and mucoepidermoid carcinoma. Carcinoma ex
      pleomorphic adenoma is difficult to identify on FNAC and in our series all 4 such
      cases on histology were considered benign on cytology.

PMID- 11952752
TI  - Fine needle aspiration in nodular fasciitis of the face.
AB  - Nodular fasciitis (NF) appears typically as a rapidly growing solitary mass which
      is most commonly located on the extremities, followed by the trunk and then the
      head and neck. NF is often suitable for fine needle aspiration (FNA), but few
      reports of NF diagnosed cytologically have been published. The purpose of this
      paper is to describe FNA cytology in three cases of nodular fasciitis. All three
      cases were located on the face.

PMID- 11952753
TI  - Is it reality or an illusion that liquid-based cytology is better than
      conventional cervical smears? Authors' reply.

PMID- 11952754
TI  - Is it reality or an illusion that liquid-based cytology is better than
      conventional cervical smears?

PMID- 11952755
TI  - Is it reality or an illusion that liquid-based cytology is better than
      conventional cervical smears?

PMID- 11952756
TI  - Is it reality or an illusion that liquid-based cytology is better than
      conventional cervical smears?

PMID- 11952758
TI  - Abstracts of the Diabetes UK Annual Professional Meeting. 13-15 March 2002.
      Birmingham, United Kingdom.

PMID- 11952761
TI  - Magnetic resonance imaging in the study of the lithium-pilocarpine model of
      temporal lobe epilepsy in adult rats.
AB  - PURPOSE: In temporal lobe epilepsy, it remains to be clarified whether
      hippocampal sclerosis is the cause or the consequence of epilepsy. We studied the
      temporal evolution of the lesions in the lithium-pilocarpine model of epilepsy in
      the rat with magnetic resonance imaging (MRI) to determine the progressive
      morphologic changes occurring before the appearance of chronic epilepsy. METHODS:
      MRI was performed on an MR scanner operating at 4.7 T. We followed the evolution
      of lesions using T(2)- and T(1)-weighted sequences before and after the injection
      of gadolinium from 2 h to 9 weeks. RESULTS: At 2 h after status epilepticus (SE),
      a blood-brain barrier breakdown could be observed only in the thalamus; it had
      disappeared by 6 h. At 24 h after SE, edema was present in the amygdala and the
      piriform and entorhinal cortices together with extensive neuronal loss; it
      disappeared progressively over a 5-day period. During the chronic phase, a
      cortical signal reappeared in all animals; this signal corresponded to gliosis,
      which appeared on glial fibrillary acidic protein (GFAP) immunohistochemically
      stained sections as hypertrophic astrocytes with thickened processes. In the
      hippocampus, the correlation between histopathology and T(2)-weighted signal
      underscored the progressive constitution of atrophy and sclerosis, starting 2
      days after SE. CONCLUSIONS: These data show the reactivity of the cortex that
      characterizes the initial step leading to the development of epilepsy and the
      late gliosis that could result from the spontaneous seizures. Moreover, it
      appears that hippocampal sclerosis progressively worsened and could be both the
      cause and the consequence of epileptic activity.

PMID- 11952762
TI  - Cardiac dysrhythmia associated with the immediate postictal state after maximal
      electroshock in freely moving rat.
AB  - PURPOSE: Cardiac autonomic changes accompany complex partial seizures and
      generalized tonic-clonic seizures, and participate, at least partially, in the
      sudden and unexpected death in epilepsy (SUDEP). The analysis of the heart rate
      variability (HRV) is one of the simplest ways of providing insight into autonomic
      functions. The entropy quantifies the repetition of complex patterns in a signal
      and refers to systems randomness, regularity, and predictability. Clinical
      investigations have reported that entropy decreases in patients with a high risk
      of sudden cardiac death. The goal of this study was to evaluate the effects of
      the maximal electroshock (MES) on the entropy of HRV, monitored in the immediate
      postictal stage in the model of the freely moving rat. METHODS: Entropy changes
      were correlated with the high and low frequencies of spectral analysis, which
      reflect the participation of the sympathetic and parasympathetic activities.
      RESULTS: MES-induced arrhythmia is characterized by an HRV increase, an imbalance
      in favor of the parasympathetic activity, and a decrease in the entropy. Entropy
      decrease was restricted to the duration of the arrhythmia, suggesting that the
      postictal arrhythmia may be associated with a higher risk of lethal cardiac
      complications. Nevertheless, entropy changes did not correlate with spectral
      changes. CONCLUSIONS: The results suggest that the imbalance demonstrated in the
      spectral domain explains only partially the contribution of each autonomic system
      in the complexity of the heart rate during the postictal state.

PMID- 11952763
TI  - Anticonvulsant actions of lamotrigine on spontaneous thalamocortical rhythms.
AB  - PURPOSE: This study examined the actions of lamotrigine (LTG) on epileptiform
      discharges resembling generalized absence (GA) and primary generalized tonic
      clonic (GTC) seizures in rat thalamocortical (TC) brain slices and attempted to
      characterize further the cellular mechanisms of action of LTG on neuronal ionic
      conductances. METHODS: Rat TC slices generated spontaneous generalized
      epileptiform discharges after perfusion with a medium containing no added Mg(2+).
      Using multiple channel extracellular field-potential recordings in thalamus and
      cortex, the effects of LTG were characterized on two principal variants of
      activity that are similar to spike-wave discharges (SWDs) of GA epilepsy and GTC
      seizure discharges. These were termed simple TC burst complexes (sTBCs) and
      complex TC burst complexes (cTBCs), respectively. With whole-cell patch-clamp
      recording techniques in acutely dissociated TC neurons, the effects of LTG on
      GABA (gamma-aminobutyric acid)(A)-receptor-mediated currents and the low
      threshold calcium current (I(T)) were examined. RESULTS: In field-potential
      recording studies in TC slices, both sTBCs and cTBCs were blocked by clinically
      relevant concentrations of LTG. In patch-clamp recording studies, LTG was found
      to be ineffective in the modulation of both GABA(A) receptors (GABARs) and I(T)
      in TC neurons. CONCLUSIONS: The efficacy of LTG on both variants of epileptiform
      discharges in TC slices clearly parallels its broad human clinical spectrum of
      action. This demonstrates that neurons within the TC system constitute one
      probable therapeutic target of LTG. However, LTG did not block either GABAR
      mediated responses or I(T) in TC neurons. Modulation of these conductances
      represent likely cellular mechanisms of action of other antiepileptic drugs
      effective in the control of GA epilepsy. This suggests that LTG may have as yet
      uncharacterized effects that could combine with its previously defined sodium
      channel-blocking actions to explain its clinical utility in the control GA
      seizures.

PMID- 11952764
TI  - Effects of the novel antiepileptic drug levetiracetam on spontaneous recurrent
      seizures in the rat pilocarpine model of temporal lobe epilepsy.
AB  - PURPOSE: Animal models in which seizures are elicited by chemical or electrical
      means are commonly used for identification and preclinical testing of novel
      antiepileptic drugs (AEDs). Such models have been successful in discovering all
      the new AEDs. However, despite the high efficacy of AEDs against elicited
      seizures in rodent models, a significant proportion of epilepsy patients with
      spontaneous recurrent seizures is resistant to these drugs. It is not known
      whether drug testing in rodent models with spontaneous recurrent seizures would
      yield a more predictive result with respect to AED efficacy in the clinic. This
      led us to test one of the novel AEDs, levetiracetam (LEV), in a rat model of
      temporal lobe epilepsy (TLE) with spontaneous recurrent seizures. METHODS: Wistar
      rats were subjected to pilocarpine-induced status epilepticus and recorded for
      spontaneous recurrent seizures in the months after pilocarpine treatment. A group
      of rats with frequent spontaneous seizures was used for the drug trial with LEV.
      The experimental protocol for drug testing in these rats was as follows. For 2
      weeks, rats received subcutaneous implantation of osmotic minipumps filled with
      saline (predrug control period), followed by a 2-week period with implantation of
      LEV-filled minipumps (drug period), after which pumps were replaced by drug-free
      pumps for 2 weeks (postdrug control period). The LEV concentration in the pumps
      during the drug period was adjusted to give daily doses resulting in the maximal
      plasma concentration range determined previously in patients with TLE during
      prolonged treatment with LEV. During the 6 weeks of the experiment in epileptic
      rats, seizures were recorded by video monitoring. RESULTS: Average seizure
      frequency during the pre- and postdrug control period in a group of eight
      epileptic rats was 21 and 25 seizures. This was reduced to an average seizure
      frequency of 8 seizures during the 2 weeks of treatment with LEV. However, the
      individual response of rats to LEV varied markedly from complete seizure control
      to no effect at all, although plasma drug levels were within the therapeutic
      range in all rats. When seizure frequency was separately calculated for the first
      and second week of treatment, the significant anticonvulsant effect determined in
      the first week was partially diminished in the second week, suggesting that
      tolerance may have developed in some of the rats. CONCLUSIONS: The data
      demonstrate that interesting results can be obtained by drug testing in epileptic
      rats, giving a more realistic prediction of clinical efficacy than results from
      drug testing in animal models with elicited seizures. Thus, although drug trials
      in rats with spontaneous recurrent seizures are laborious and time-consuming,
      such trials should be added to the preclinical characterization of novel AEDs.

PMID- 11952765
TI  - Acetoacetate, acetone, and dibenzylamine (a contaminant in l-(+)-beta
      hydroxybutyrate) exhibit direct anticonvulsant actions in vivo.
AB  - PURPOSE: To investigate whether ketone bodies are directly anticonvulsant.
      METHODS: We tested the effects of acetoacetate (ACA), acetone, and both
      stereoisomers, D-(-)- and L-(+), of beta-hydroxybutyrate (BHB) on sensory-evoked
      seizures in Frings audiogenic seizure-susceptible mice. RESULTS: We found that
      these ketone bodies, with the exception of the D-(-)-isomer of BHB, were
      anticonvulsant in this model. Furthermore, with gas chromatography-mass
      spectrometry, we confirmed that the activity of L-(+)-BHB was due to
      dibenzylamine, a chemical contaminant. CONCLUSIONS: Our data indicate that the
      anticonvulsant efficacy of the ketogenic diet may be due in part to the direct
      actions of ACA and acetone.

PMID- 11952766
TI  - Mutational analysis of nicotinic acetylcholine receptor beta2 subunit gene
      (CHRNB2) in a representative cohort of Italian probands affected by autosomal
      dominant nocturnal frontal lobe epilepsy.
AB  - Twenty-four autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) probands
      were analyzed for the presence of V287L and V287M mutations in the CHRNB2 gene,
      which have been recently associated with the disease. In all patients, the
      involvement of the two additional loci reported as being associated with ADNFLE
      (CHRNA4 gene and chromosome 15q24 region) had been previously excluded.
      Mutational screening was performed by sequencing a polymerase chain reaction
      amplified CHRNB2 DNA fragment, spanning the whole exon 5, which contains the
      V287L and V287M mutations and codes for approximately 65% of the mature protein.
      In none of the patients were mutations in the analyzed region of CHRNB2 found.
      These data, obtained in the largest ADNFLE cohort so far analyzed, demonstrate
      the rarity of the identified CHRNB2 mutations in ADNFLE patients.

PMID- 11952767
TI  - The importance of drug interactions in epilepsy therapy.
AB  - Long-term antiepileptic drug (AED) therapy is the reality for the majority of
      patients diagnosed with epilepsy. One AED will usually be sufficient to control
      seizures effectively, but a significant proportion of patients will need to
      receive a multiple AED regimen. Furthermore, polytherapy may be necessary for the
      treatment of concomitant disease. The fact that over-the-counter drugs and
      nutritional supplements are increasingly being self-administered by patients also
      must be considered. Therefore the probability of patients with epilepsy
      experiencing drug interactions is high, particularly with the traditional AEDs,
      which are highly prone to drug interactions. Physicians prescribing AEDs to
      patients with epilepsy must, therefore, be aware of the potential for drug
      interactions and the effects (pharmacokinetic and pharmacodynamic) that can occur
      both during combination therapy and on drug discontinuation. Although
      pharmacokinetic interactions are numerous and well described, pharmacodynamic
      interactions are few and usually concluded by default. Perhaps the most
      clinically significant pharmacodynamic interaction is that of lamotrigine (LTG)
      and valproic acid (VPA); these drugs exhibit synergistic efficacy when
      coadministered in patients with refractory partial and generalised seizures.
      Hepatic metabolism is often the target for pharmacokinetic drug interactions, and
      enzyme-inducing drugs such as phenytoin (PHT), phenobarbitone (PB), and
      carbamazepine (CBZ) will readily enhance the metabolism of other AEDs [e.g., LTG,
      topiramate (TPM), and tiagabine (TGB)]. The enzyme-inducing AEDs also enhance the
      metabolism of many other drugs (e.g., oral contraceptives, antidepressants, and
      warfarin) so that therapeutic efficacy of coadministered drugs is lost unless the
      dosage is increased. VPA inhibits the metabolism of PB and LTG, resulting in an
      elevation in the plasma concentrations of the inhibited drugs and consequently an
      increased risk of toxicity. The inhibition of the metabolism of CBZ by VPA
      results in an elevation of the metabolite CBZ-epoxide, which also increases the
      risk of toxicity. Other examples include the inhibition of PHT and CBZ metabolism
      by cimetidine and CBZ metabolism by erythromycin. In recent years, a more
      rational approach has been taken with regard to metabolic drug interactions
      because of our enhanced understanding of the cytochrome P450 system that is
      responsible for the metabolism of many drugs, including AEDs. The review briefly
      discusses the mechanisms of drug interactions and then proceeds to highlight some
      of the more clinically relevant drug interactions between AEDs and between AEDs
      and non-AEDs. Understanding the fundamental principles that contribute to a drug
      interaction may help the physician to better anticipate a drug interaction and
      allow a graded and planned therapeutic response and, therefore, help to enhance
      the management of patients with epilepsy who may require treatment with
      polytherapy regimens.

PMID- 11952768
TI  - Influence on ictal seizure semiology of rapid withdrawal of carbamazepine and
      valproate in monotherapy.
AB  - PURPOSE: To quantify changes in ictal seizure semiology during rapid withdrawal
      of carbamazepine (CBZ) and valproate (VPA) from a monoregimen in presurgical
      evaluation. METHODS: Therapeutic intensive seizure analysis (TISA) with video-EEG
      monitoring was used in 33 patients with pharmacoresistant partial epilepsy
      undergoing complete withdrawal of CBZ (20 patients) or VPA (13 patients) from a
      monoregimen. Monitoring phases included a 3-day baseline phase, a 3-day rapid
      antiepileptic drug (AED) withdrawal phase, and another 3-day AED-free phase with
      AEDs in subtherapeutic levels. Seizure variables as complete processes and their
      various elements (ictal signs) were analyzed, including duration (seconds),
      intensity (on a scale of 0 to 3), frequency (number per 3 days), and total
      duration of seizures and ictal signs in 3 days (seconds). The localization of
      seizure patterns on ictal EEG recording (EEG seizure onset) and the first
      appearing clinical ictal phenomena (initial ictal signs) were recorded. RESULTS:
      A total of 188 seizures in the CBZ group and 57 seizures in the VPA group were
      investigated. Compared with the baseline phase, the CBZ group showed increases in
      duration, frequency of seizures, various ictal signs, and secondarily generalized
      tonic and clonic signs during the following two phases. Significantly increased
      values of the VPA group were observed in seizure duration and frequency of
      hypermotoric phenomena during the AED-free phase. More patients in the CBZ group
      had secondarily generalized clonic signs during the AED-free phase. EEG seizure
      onset and initial ictal signs showed no obvious changes between study phases.
      CONCLUSIONS: Withdrawal of CBZ is followed more quickly by an increase of seizure
      frequency and severity than is the case for VPA withdrawal. Both CBZ and VPA
      withdrawal influences seizure propagation rather than the seizure-onset
      characteristics, which speaks in favor of its use in presurgical evaluation.

PMID- 11952769
TI  - Occurrence of psychosis in patients with epilepsy randomized to tiagabine or
      placebo treatment.
AB  - PURPOSE: Patients with drug-resistant epilepsy have a higher incidence of
      psychiatric problems and possibly greater intolerance to antiepileptic drugs
      (AEDs) than do other patients with epilepsy. Concern has been raised that gamma
      aminobutyric acid (GABA)ergic drugs may be associated with treatment-emergent
      psychosis. Tiagabine (TGB; Gabitril), a new AED that blocks synaptic GABA uptake,
      was developed in trials of drug-resistant patients with epilepsy. We conducted ad
      hoc analyses of adverse events, drug intolerance, and treatment response to
      evaluate the association between TGB treatment and psychosis and whether
      psychiatric history might be predictive of tolerance or effectiveness of this
      GABAergic drug. METHODS: Data were analyzed from two multicenter, randomized,
      double-blind, placebo-controlled trials of add-on TGB therapy (32 or 56 mg daily)
      in 554 adolescents and adults with complex partial seizures (CPSs). After an 8-
      or 12-week baseline phase, double-blind treatment consisted of a 4-week titration
      period (with TGB dose gradually increased to 32 or 56 mg daily) and an 8- or 12
      week fixed-dose period. Adverse events commonly associated with psychosis were
      evaluated. Treatment intolerance and effectiveness (> or =50% reduction in CPS
      rate) were compared among patients with and without psychiatric histories.
      RESULTS: Psychotic symptoms (hallucinations) were observed in three (0.8%) of 356
      TGB-treated patients and none of 198 placebo-treated patients (p = 0.556, NS).
      Statistical analysis showed no interaction between psychiatric history and drug
      intolerance or treatment outcome. CONCLUSIONS: TGB administration appears to
      carry no significant increased risk of treatment-emergent psychosis. Psychiatric
      history was not predictive of the tolerance or effectiveness of the drug.

PMID- 11952770
TI  - Topiramate in patients with learning disability and refractory epilepsy.
AB  - PURPOSE: Management of seizures in learning disabled people is challenging. This
      prospective study explored the efficacy and tolerability of adjunctive topiramate
      (TPM) in patients with learning disability and refractory epilepsy attending a
      single centre. METHODS: Sixty-four patients (36 men, 28 women, aged 16-65 years)
      were begun on adjunctive TPM after a 3-month prospective baseline on unchanged
      medication. Efficacy end points were reached when a consistent response was
      achieved over a 6-month period at optimal TPM dosing. These were seizure freedom
      or > or =50% seizure reduction (responder). Appetite, behaviour, alertness, and
      sleep were assessed by caregivers throughout the study. RESULTS: Sixteen (25%)
      patients became seizure free with adjunctive TPM. There were 29 (45%) responders.
      A further 10 (16%) patients experiencing a more modest improvement in seizure
      control continued on treatment at the behest of their family and/or caregivers.
      TPM was discontinued in the remaining nine (14%) patients, mainly because of side
      effects. Final TPM doses and plasma concentrations varied widely among the
      efficacy outcome groups. Many patients responding well to adjunctive TPM did so
      on < or =200 mg daily. Mean carer scores did not worsen with TPM therapy.
      CONCLUSIONS: TPM was effective as add-on therapy in learning-disabled people with
      difficult-to-control epilepsy. Seizure freedom is a realistic goal in this
      population.

PMID- 11952771
TI  - Ictal EEG patterns in band heterotopia.
AB  - Band heterotopia (BH) or "double cortex" syndrome is a neuronal migration
      disorder resulting in a diffuse band of subcortical grey matter and variable
      abnormality of the overlying cortex. Patients with BH have a spectrum of
      psychomotor delay and seizures. Associated epileptic syndromes and interictal EEG
      findings have been described, but ictal EEG patterns are lacking. METHODS: We
      describe the clinical, interictal, and ictal EEG findings in two girls with BH
      and intractable seizures. RESULTS: Ictal EEG patterns correlated well with
      clinical seizure types, and did not have features unique to BH. Similarly,
      seizure behaviors and interictal EEG findings were typical of those seen in
      symptomatic generalized epilepsies. CONCLUSIONS: Despite evidence implicating the
      ectopic grey matter in seizure discharges, we conclude that seizure semiology and
      associated ictal EEG patterns in BH are no different from those seen in other
      causes of symptomatic generalized epilepsies.

PMID- 11952772
TI  - The usefulness of subtraction ictal SPECT coregistered to MRI in single- and dual
      headed SPECT cameras in partial epilepsy.
AB  - PURPOSE: To prove the clinical usefulness of SISCOM and compare SISCOM images
      derived from single- and dual-headed single-photon computed tomography (SPECT)
      cameras for localization of partial epileptic seizures. METHODS: We
      retrospectively studied 38 partial epilepsy patients, using subtraction SPECT
      coregistered to magnetic resonance imaging (MRI; SISCOM). SPECT imaging of the
      first 15 patients was performed by single-headed camera, and the next 23 patients
      by dual-headed camera. Side-by-side ictal-interictal SPECT evaluation and SISCOM
      images were blindly reviewed and classified as either localizing to one of 16
      sites or nonlocalizing. A third reviewer evaluated cases of disagreement between
      primary reviewers. Results were compared with seizure localization by any of the
      following three traditional techniques: surgical outcome, invasive, and
      noninvasive video-EEG monitoring. The results from the single- and dual-headed
      SPECT cameras were compared. RESULTS: Reviewers localized areas of hyperperfusion
      with SISCOM images more often than with side-by-side SPECT evaluation (71.0 vs.
      47.4%; p = 0.01). When we compared results of SPECT evaluation with traditional
      techniques, SISCOM showed greater concordance than side-by-side SPECT evaluation
      (60.53 vs. 36.84%; p = 0.006). There were no differences in localization between
      images derived from single- and dual-headed cameras. Concordance of seizure
      localization, compared with traditional techniques, also was not different
      between these groups [kappa = 0.38, 95% confidence interval (CI), 0.18-0.58] vs.
      kappa = 0.63, 95% CI (0.45-0.81)]. CONCLUSIONS: SISCOM is a worthwhile technique
      for preoperative evaluation in partial epilepsy patients and improves the
      sensitivity and specificity of seizure localization of SPECT images derived from
      both single- and dual-headed SPECT cameras.

PMID- 11952773
TI  - Surgical implications of neuromagnetic spike localization in temporal lobe
      epilepsy.
AB  - PURPOSE: To investigate the clinical usefulness of magnetoencephalography (MEG)
      as a guide to the surgical treatment of temporal lobe epilepsy (TLE). METHODS:
      Preoperative spike localization by MEG was compared with seizure outcome and
      postoperative spike localization at 12 months after resective surgery in 16
      patients with TLE. Spike localization was classified into anterior temporal (AT)
      and non-AT localization in 11 patients without neocortical lesion treated with
      anterior temporal lobectomy (ATL); and lesion and lobar localization in five
      patients with neocortical lesion treated with lesionectomy (n = 3) or
      lesionectomy with medial temporal resection (n = 2). RESULTS: All five patients
      with AT localization became seizure free and spike free after surgery. Among the
      six patients with non-AT localization, two became seizure free and spike free,
      two became seizure free with residual spikes, one had residual seizures but no
      spikes, and one had both residual seizures and spikes. All three patients with
      lesion localization and two with lobar localization had favorable seizure outcome
      and became spike free after surgery. CONCLUSIONS: MEG spike localization can
      identify neocortical sources remote from the presumed epileptogenic area.
      Favorable seizure outcome can be expected in patients with AT localization after
      ATL and patients with lesion localization after lesionectomy. In contrast, non-AT
      localization indicates either nonmedial TLE or spike propagation to the posterior
      and extratemporal neocortex. Similarly, lobar localization indicates spike
      propagation from an epileptogenic lesion or extensive epileptogenicity. Patients
      with non-AT localization or lobar localization should undergo intensive
      evaluations, such as intracranial EEG, for improved seizure outcome.

PMID- 11952774
TI  - Optimizing epilepsy surgery with intraoperative MR imaging.
AB  - PURPOSE: The surgical treatment of medically intractable temporal lobe epilepsy
      includes the resection of temporal lobe structures. Although the reported seizure
      free outcomes are highly variable, there is growing evidence that the extent of
      resection of the mesiotemporal lobe directly correlates with seizure control.
      METHODS: A moveable, high-field intraoperative magnetic resonance (MR) system was
      used to monitor and optimize the resection of the amygdala and hippocampus in 14
      epilepsy patients. Fourteen patients with intractable seizures of temporal lobe
      origin underwent standard preoperative investigations including MR imaging, EEG
      telemetry, single-photon emission computed tomography, and neuropsychologic and
      sodium amytal testing. Anterior temporal lobectomy was performed on 10 patients,
      whereas four were treated with selective amygdalohippocampectomy. Intraoperative
      electrocorticography was applied as required. For all procedures, the objective
      was to resect the amygdala completely, and hippocampus to the posterior margin of
      the brainstem. RESULTS: Interdissection intraoperative MR imaging taken when
      optimal resection was thought to have been achieved revealed residual unresected
      amygdala or hippocampus in seven of 14 patients. An unexpected acute hematoma was
      found in one patient. At 17 months' follow-up, 13 (93%) of 14 patients are
      seizure free or have significantly improved seizure control. CONCLUSIONS: The
      mobile high-field intraoperative MR system provides high-resolution images
      without restriction on surgical instruments or techniques. The ability to
      identify and resect residual mesial temporal lobe targets before craniotomy
      closure is of potentially tremendous value in optimizing seizure control.

PMID- 11952775
TI  - Standardization of amygdalohippocampectomy with intraoperative magnetic resonance
      imaging: preliminary experience.
AB  - PURPOSE: Intraoperative magnetic resonance imaging (IMRI) is an extremely useful
      neurosurgical tool in surgeries in which the extent of resection is known to have
      a significant impact on outcome. Residual hippocampus is the most common cause of
      recurrent seizures after temporal lobectomy for medial temporal lobe epilepsy.
      Although the risk/benefit ratio of a policy of universal radical hippocampal
      resection is not known, we hypothesized that IMRI would aid in the intraoperative
      assessment of the extent of hippocampal resection and assist in accomplishing a
      complete hippocampectomy. METHODS: Five consecutive patients with medically
      intractable medial temporal lobe epilepsy underwent a radical
      amygdalohippocampectomy as part of the their surgery for epilepsy. IMRI was used
      before surgery and after an initial resection. The quality of images was
      assessed. Postoperative MR images were evaluated by a radiologist to determine
      the extent of resection of the amygdala, hippocampus, and parahippocampal gyrus.
      RESULTS: There were no perioperative infections. After a mean follow-up of 10
      months, all patients are seizure free. T(1)-weighted coronal intraoperative
      images were judged adequate at visualizing the medial structures in all patients.
      T(2) and fluid-attenuated inversion recovery (FLAIR) images did not provide
      useful information. Postoperative MR images indicated that a complete
      hippocampectomy had been achieved in all patients. CONCLUSIONS: IMRI is a useful
      adjunct in the surgical treatment of medial temporal lobe epilepsy and perhaps
      the most reliable method of standardizing a complete hippocampectomy. T(1)
      weighted coronal images are the most helpful sequence.

PMID- 11952776
TI  - Is refractory epilepsy preventable?
AB  - About a third of the patients diagnosed with epilepsy will not be fully
      controlled with antiepileptic drugs (AEDs), and many of them will have frequent
      and disabling seizures. These patients will undergo multiple drug trials, most
      often without complete seizure remission. Moreover, refractory epilepsy is
      associated with increased morbidity (from seizures and medications), social
      isolation, unemployment, and overall reduced quality of life. There is evidence
      that refractory epilepsy can be a progressive disorder, which, if controlled
      early, might never develop into a full syndrome with all of its associated
      sequelae. The difficulty lies in identifying at an early stage patients who are
      likely to progress to intractability. No currently known markers enable
      clinicians to make this identification with confidence. Advances in
      pharmacogenomics and our understanding of pharmacologic responsiveness in
      epilepsy may change this situation. Even now, we are able to identify many
      patients with a poor prognosis earlier than before, particularly in the pediatric
      population, in which syndromic classification may provide an approach to predict
      intractability. The early initiation of aggressive therapy may improve outcome
      and overall quality of life.

PMID- 11952777
TI  - Survival of patients with epilepsy: an estimate of the mortality risk.
AB  - PURPOSE: To investigate the extent and causes of the differences in mortality
      found in studies on mortality in epilepsy based on a quantitative review of the
      literature. METHODS: We used MEDLINE database and Cumulative Index Medicus for
      1960-2001, Excerpta Medica for 1948-1965, and relevant journals and
      bibliographies. We selected comparative studies investigating mortality in
      epilepsy patients conducted in the last 100 years. The Standardized Mortality
      Ratio (SMR) was selected as primary outcome. Nineteen studies were included.
      Pooled estimates were precision weighted and tested for homogeneity. Sources of
      variability between risk estimates were explored by using multivariate fixed
      effects models. RESULTS: SMRs ranged from 1.3 to 9.3. Risk estimates proved
      heterogeneous (chi-square test statistic: 1,177; df = 18; p < 0.001). The most
      important determinant was "source population," explaining half of the variance of
      the estimates (R(2), 0.47; p = 0.006). SMRs in community studies ranged from 1.3
      to 3.1, and for institutionalized populations, from 1.9 to 5.1. CONCLUSIONS: Our
      results show that the mortality risk in patients with epilepsy is dependent on
      source population of patients. Within the different source populations,
      considerable unexplained variance remains. Hence no uniform summary estimate for
      the elevated mortality could be determined.

PMID- 11952778
TI  - Topiramate enhances the risk of valproate-associated side effects in three
      children.
AB  - PURPOSE: We present three children with severe therapy-refractory epilepsy who
      tolerated valproate (VPA) well in various combinations with other antiepileptic
      drugs (AEDs) but developed typical VPA side effects in combination with
      topiramate (TPM). METHODS: The clinical symptoms began with apathy in all three
      children; two of them also had hypothermia. Furthermore all children had elevated
      blood ammonia levels, one child in combination with increased liver transaminases
      and one with thrombocytopenia. RESULTS: All children recovered completely after
      discontinuation of VPA or TPM. CONCLUSIONS: TPM seems likely to enhance the risk
      of side effects usually attributed to VPA and not described in TPM monotherapy.
      Our case reports suggest that possible adverse effects of VPA should be given
      particular attention when VPA is combined with TPM.

PMID- 11952779
TI  - Oxcarbazepine and hepatic porphyria.

PMID- 11952781
TI  - Epoxidation of benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1 in reconstituted
      membranes. Effects of charge and nonbilayer phase propensity of the membrane.
AB  - Human cytochrome P4501A1 (CYP1A1) is one of the key enzymes in the bioactivation
      of environmental pollutants such as benzo[a]pyrene (B[a]P) and other polycyclic
      aromatic hydrocarbons. To evaluate the effect of membrane properties and distinct
      phospholipids on the activity of human CYP1A1 purified insect cell-expressed
      human CYP1A1 and of human NADPH-P450 reductase were reconstituted into
      phospholipid vesicle membranes. Conversion rates of up to 36 pmol x min(-1) x
      pmol(-1) CYP1A1 of the enantiomeric promutagens (-)- and (+)-trans-7,8-dihydroxy
      7,8-dihydro-B[a]P (7,8-diol) to the genotoxic diolepoxides were achieved. The
      highest rates were obtained when negatively charged lipids such as
      phosphatidylserine and phosphatidylinositol and/or nonbilayer phospholipids such
      as phosphatidylethanolamine were present in the membrane together with neutral
      lipids. Both Vmax and Km values were changed. This suggests a rather complex
      mechanism of stimulation which might include altered substrate binding as well as
      more effective interaction between CYP1A1 and NADPH-P450 reductase. Furthermore,
      the ratio of r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydro-B[a]P (DE2) to r
      7,t-8-dihydroxy-c-9,10-epoxy-7,8,9,10-tetrahydro-B[a]P (DE1) formed from (-)-7,8
      diol was significantly increased by the introduction of anionic lipids, but not
      by that of nonbilayer lipids. Thus, charged lipids affect the stereoselectivity
      of the epoxidation by leading to the formation of a larger amount of the ultimate
      mutagen DE2 than of DE1, which is far less carcinogenic. These data suggest that
      membrane properties such as negative charge and nonbilayer phase propensity are
      important for the efficiency and selectivity of enzymatic function of human
      CYP1A1.

PMID- 11952782
TI  - Functional similarities between the small heat shock proteins Mycobacterium
      tuberculosis HSP 16.3 and human alphaB-crystallin.
AB  - Mycobacterium tuberculosis heat shock protein 16.3 (MTB HSP 16.3) accumulates as
      the dominant protein in the latent stationary phase of tuberculosis infection.
      MTB HSP 16.3 displays several characteristics of small heat shock proteins
      (sHsps): its expression is increased in response to stress, it protects against
      protein aggregation in vitro, and it contains the core 'alpha-crystallin' domain
      found in all sHsps. In this study we characterized the chaperone activity of
      recombinant MTB HSP 16.3 in several different assays and compared the results to
      those obtained with recombinant human alphaB-crystallin, a well characterized
      member of the sHsp family. Recombinant MTB HSP 16.3 was expressed in Escherichia
      coli and purified to apparent homogeneity. Similar to alphaB-crystallin, MTB
      HSP16.3 suppressed citrate synthase aggregation and in the presence of 3.5 mm ATP
      the chaperone activity was enhanced by twofold. ATP stabilized MTB HSP 16.3
      against proteolysis by chymotrypsin, and no effect was observed with ATPgammaS, a
      nonhydrolyzable analog of ATP. Increased expression of MTB HSP 16.3 resulted in
      protection against thermal killing in E. coli at 48 degrees C. While the sequence
      similarity between human alphaB-crystallin and MTB HSP 16.3 is only 18%, these
      results suggest that the functional similarities between these proteins
      containing the core 'alpha-crystallin' domain are much closer.

PMID- 11952783
TI  - Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and
      functional mutation.
AB  - Aquaporin adipose (AQPap), which we identified from human adipose tissue, is a
      glycerol channel in adipocyte [Kishida et al. (2000) J. Biol. Chem. 275, 20896
      20902]. In the current study, we determined the genomic structure of the human
      AQPap gene, and identified three AQPap-like genes that resembled (approximately
      95%) AQPap, with little expression in human tissues. The AQPap promoter contained
      a putative peroxisome proliferator response element (PPRE) at -46 to -62, and a
      putative insulin response element (IRE) at -542/-536. Deletion of the PPRE
      abolished the pioglitazone-mediated induction of AQPap promoter activity in 3T3
      L1 adipocytes. Deletion and single base pair substitution analysis of the IRE
      abolished the insulin-mediated suppression of the human AQPap gene. Analysis of
      AQPap sequence in human subjects revealed three missense mutations (R12C, V59L
      and G264V), and two silent mutations (A103A and G250G). The cRNA injection of the
      missense mutants into Xenopus oocytes revealed the absence of the activity to
      transport glycerol and water in the AQPap-G264V protein. In the subject
      homozygous for AQPap-G264V, exercise-induced increase in plasma glycerol was not
      observed in spite of the increased plasma noradrenaline. We suggest that AQPap is
      responsible for the increase of plasma glycerol during exercise in humans.

PMID- 11952784
TI  - Binding of hemolin to bacterial lipopolysaccharide and lipoteichoic acid. An
      immunoglobulin superfamily member from insects as a pattern-recognition receptor.
AB  - Hemolin, a plasma protein from lepidopteran insects, is composed of four
      immunoglobulin domains. Its synthesis is induced by microbial challenge. We
      investigated the biological functions of hemolin in Manduca sexta. It was found
      to bind to the surface of bacteria and yeast, and caused these micro-organisms to
      aggregate. Hemolin was demonstrated to bind to lipopolysaccharide (LPS) from Gram
      negative bacteria and to lipoteichoic acid from Gram-positive bacteria. Binding
      of hemolin to smooth-type forms of LPS was competed for efficiently by
      lipoteichoic acid and by rough mutant (Ra and Rc) forms of LPS, which differ in
      polysaccharide length. Binding of hemolin to LPS was partially inhibited by
      calcium and phosphate. Hemolin bound to the lipid A component of LPS, and this
      binding was completely blocked by free phosphate. Our results suggest that
      hemolin has two binding sites for LPS, one that interacts with the phosphate
      groups of lipid A and one that interacts with the O-specific antigen and the
      outer-core carbohydrates of LPS. The binding properties of M. sexta hemolin
      suggest that it functions as a pattern-recognition protein with broad specificity
      in the defense against micro-organisms.

PMID- 11952785
TI  - Residues near the N-terminus of protein B control autocatalytic proteolysis and
      the activity of soluble methane mono-oxygenase.
AB  - Soluble methane mono-oxygenase (sMMO) of Methylococcus capsulatus (Bath)
      catalyses the O2-dependent and NAD(P)H-dependent oxygenation of methane and
      numerous other substrates. During purification, the sMMO enzyme complex, which
      comprises three components and has a molecular mass in excess of 300 kDa, becomes
      inactivated because of cleavage of just 12 amino acids from the N-terminus of
      protein B, which is the smallest component of sMMO and the only one without
      prosthetic groups. Here we have shown that cleavage of protein B, to form the
      inactive truncated protein B', continued to occur when intact protein B was
      repeatedly separated from protein B' and all detectable contaminants, giving
      compelling evidence that the protein was cleaved autocatalytically. The rate of
      autocatalytic cleavage decreased when the residues flanking the cleavage site
      were mutated, but the position of cleavage was unaltered. Analysis of a series of
      incremental truncates showed that residue(s) essential for the activity of sMMO,
      and important in determining the stability of protein B, lay in the region Ser4
      Tyr7. Protein B was shown to possess intrinsic nucleophilic activity, which we
      propose initiates the cleavage reaction via a novel mechanism. Proteins B and B'
      were detected in approximately equal amounts in the cell, showing that truncation
      of protein B is biologically relevant. Increasing the growth-medium copper
      concentration, which inactivates sMMO, did not alter the extent of in vivo
      cleavage, therefore the conditions under which cleavage of protein B may fulfil
      its proposed role as a regulator of sMMO remain to be identified.

PMID- 11952786
TI  - The fate of newly synthesized V-ATPase accessory subunit Ac45 in the secretory
      pathway.
AB  - The vacuolar H+-ATPase (V-ATPase) is a multimeric enzyme complex that acidifies
      organelles of the vacuolar system in eukaryotic cells. Proteins that interact
      with the V-ATPase may play an important role in controlling the intracellular
      localization and activity of the proton pump. The neuroendocrine-enriched V
      ATPase accessory subunit Ac45 may represent such a protein as it has been shown
      to interact with the membrane sector of the V-ATPase in only a subset of
      organelles. Here, we examined the fate of newly synthesized Ac45 in the secretory
      pathway of a neuroendocrine cell. A major portion of intact approximately 46-kDa
      Ac45 was found to be N-linked glycosylated to approximately 62 kDa and a minor
      fraction to approximately 64 kDa. Trimming of the N-linked glycans gave rise to
      glycosylated Ac45-forms of approximately 61 and approximately 63 kDa that are
      cleaved to a C-terminal fragment of 42-44 kDa (the deglycosylated form is
      approximately 23 kDa), and a previously not detected approximately 22-kDa N
      terminal cleavage fragment (the deglycosylated form is approximately 20 kDa).
      Degradation of the N-terminal fragment is rapid, does not occur in lysosomes and
      is inhibited by brefeldin A. Both the N- and C-terminal fragment pass the medial
      Golgi, as they become partially endoglycosidase H resistant. The Ac45 cleavage
      event is a relatively slow process (half-life of intact Ac45 is 4-6 h) and takes
      place in the early secretory pathway, as it is not affected by brefeldin A and
      monensin. Tunicamycin inhibited N-linked glycosylation of Ac45 and interfered
      with the cleavage process, suggesting that Ac45 needs proper folding for the
      cleavage to occur. Together, our results indicate that Ac45 folding and cleavage
      occur slowly and early in the secretory pathway, and that the cleavage event may
      be linked to V-ATPase activation.

PMID- 11952787
TI  - Purification, characterization and biosynthesis of parabutoxin 3, a component of
      Parabuthus transvaalicus venom.
AB  - A novel peptidyl inhibitor of voltage-gated K+ channels, named parabutoxin 3
      (PBTx3), has been purified to homogeneity from the venom of Parabuthus
      transvaalicus. This scorpion toxin contains 37 residues, has a mass of 4274 Da
      and displays 41% identity with charybdotoxin (ChTx, also called 'alpha-KTx1.1').
      PBTx3 is the tenth member (called 'alpha-KTx1.10') of subfamily 1 of K+ channel
      blocking peptides known thus far. Electrophysiological experiments using Xenopus
      laevis oocytes indicate that PBTx3 is an inhibitor of Kv1 channels (Kv1.1, Kv1.2,
      Kv1.3), but has no detectable effects on Kir-type and ERG-type channels. The
      dissociation constants (Kd) for Kv1.1, Kv1.2 and Kv1.3 channels are,
      respectively, 79 microm, 547 nm and 492 nm. A synthetic gene encoding a PBTx3
      homologue was designed and expressed as a fusion protein with the maltose-binding
      protein (MBP) in Escherichia coli. The recombinant protein was purified from the
      bacterial periplasm compartment using an amylose affinity resin column, followed
      by a gel filtration purification step and cleavage by factor Xa (fXa) to release
      the recombinant toxin peptide (rPBTx3). After final purification and refolding,
      rPBTx3 was shown to be identical to the native PBTx3 with respect to HPLC
      retention time, mass spectrometric analysis and functional properties. The three
      dimensional structure of PBTx3 is proposed by homology modelling to contain a
      double-stranded antiparallel beta sheet and a single alpha-helix, connected by
      three disulfide bridges. The scaffold of PBTx3 is homologous to most other alpha
      KTx scorpion toxins.

PMID- 11952788
TI  - Structural requirements for the apical sorting of human multidrug resistance
      protein 2 (ABCC2).
AB  - The human multidrug resistance protein 2 (MRP2, symbol ABCC2) is a polytopic
      membrane glycoprotein of 1545 amino acids which exports anionic conjugates across
      the apical membrane of polarized cells. A chimeric protein composed of C-proximal
      MRP2 and N-proximal MRP1 localized to the apical membrane of polarized Madin
      Darby canine kidney cells (MDCKII) indicating involvement of the carboxy-proximal
      part of human MRP2 in apical sorting. When compared to other MRP family members,
      MRP2 has a seven-amino-acid extension at its C-terminus with the last three amino
      acids (TKF) comprising a PDZ-interacting motif. In order to analyze whether this
      extension is required for apical sorting of MRP2, we generated MRP2 constructs
      mutated and stepwise truncated at their C-termini. These constructs were fused
      via their N-termini to green fluorescent protein (GFP) and were transiently
      transfected into polarized, liver-derived human HepG2 cells. Quantitative
      analysis showed that full-length GFP-MRP2 was localized to the apical membrane in
      73% of transfected, polarized cells, whereas it remained on intracellular
      membranes in 27% of cells. Removal of the C-terminal TKF peptide and stepwise
      deletion of up to 11 amino acids did not change this predominant apical
      distribution. However, apical localization was largely impaired when GFP-MRP2 was
      C-terminally truncated by 15 or more amino acids. Thus, neither the PDZ
      interacting TKF motif nor the full seven-amino-acid extension were necessary for
      apical sorting of MRP2. Instead, our data indicate that a deletion of at least 15
      C-terminal amino acids impairs the localization of MRP2 to the apical membrane of
      polarized cells.

PMID- 11952790
TI  - Structural basis for poor uracil excision from hairpin DNA. An NMR study.
AB  - Two-dimensional NMR and molecular dynamics simulations have been used to
      determine the three-dimensional structures of two hairpin DNA structures: d
      CTAGAG GATCCUTTTGGATCCT (abbreviated as U1-hairpin) and d-CTAGAGGATCCTTUTGGATCCT
      (abbreviated as U3-hairpin). The 1H resonances of both of these hairpin
      structures have been assigned almost completely. NMR restrained molecular
      dynamics and energy minimization procedures have been used to describe the three
      dimensional structures of these hairpins. This study and concurrent NMR
      structural studies on two other d-CTAGAGGA TCCTUTTGGATCCT (abbreviated as U2
      hairpin) and d-CTAGAGGATCCTTTUGGATCCT (abbreviated as U4-hairpin) have shed light
      upon various interactions reported between Echerichia coli uracil DNA glycosylase
      (UDG) and uracil-containing DNA. The backbone torsion angles, which partially
      influence the local conformation of U12 and U14 in U1 and U3-hairpins,
      respectively, are probably locked in the trans conformation as in the case of U13
      in the U2-hairpin. Such a stretched-out backbone conformation in the vicinity of
      U12 and U14 is thought to be the reason why the Km value is poor for U1- and U3
      hairpins as it is for the U2-hairpin. Furthermore, the bases U12 and U14 in both
      U1- and U3-hairpins adopt an anti conformation, in contrast with the base
      conformation of U13 in the U2-hairpin, which adopts a syn conformation. The clear
      discrepancy observed in the U-base orientation with respect to the sugar moieties
      could explain why the Vmax value is 10- to 20-fold higher for the U1- and U3
      hairpins compared with the U2-hairpin. Taken together, these observations support
      our interpretation that the unfavourable backbone results in a poor Km value,
      whereas the unfavourable nucleotide conformation results in a poor Vmax value.
      These two parameters therefore make the U1- and U3-hairpins better substrates for
      UDG compared with the U2-hairpin, as reported earlier [Kumar, N. V. & Varshney,
      U. (1997) Nucleic Acids Res. 25, 2336-2343.].

PMID- 11952789
TI  - Role of the N- and C-terminal regions of the PufX protein in the structural
      organization of the photosynthetic core complex of Rhodobacter sphaeroides.
AB  - The core complex of Rhodobacter sphaeroides is formed by the association of the
      light-harvesting antenna 1 (LH1) and the reaction center (RC). The PufX protein
      is essential for photosynthetic growth; it is located within the core in a 1 : 1
      stoichiometry with the RC. PufX is required for a fast ubiquinol exchange between
      the Q(B) site of the RC and the Qo site of the cytochrome bc1 complex. In vivo
      the LH1-PufX-RC complex is assembled in a dimeric form, where PufX is involved as
      a structural organizer. We have modified the PufX protein at the N and the C
      terminus with progressive deletions. The nine mutants obtained have been
      characterized for their ability for photosynthetic growth, the insertion of PufX
      in the core LH1-RC complex, the stability of the dimers and the kinetics of flash
      induced reduction of cytochrome b561 of the cytochrome bc1 complex. Deletion of
      18 residues at the N-terminus destabilizes the dimer in vitro without preventing
      photosynthetic growth. The dimer (or a stable dimer) does not seem to be a
      necessary requisite for the photosynthetic phenotype. Partial C-terminal
      deletions impede the insertion of PufX, while the complete absence of the C
      terminus leads to the insertion of a PufX protein composed of only its first 53
      residues and does not affect the photosynthetic growth of the bacterium. Overall,
      the results point to a complex role of the N and C domains in the structural
      organization of the core complex; the N-terminus is suggested to be responsible
      mainly for dimerization, while the C-terminus is thought to be involved mainly in
      PufX assembly.

PMID- 11952791
TI  - Purification and characterization of a membrane-bound enzyme complex from the
      sulfate-reducing archaeon Archaeoglobus fulgidus related to heterodisulfide
      reductase from methanogenic archaea.
AB  - Heterodisulfide reductase (Hdr) is a unique disulfide reductase that plays a key
      role in the energy metabolism of methanogenic archaea. The genome of the sulfate
      reducing archaeon Archaeoglobus fulgidus encodes several proteins of unknown
      function with high sequence similarity to the catalytic subunit of Hdr. Here we
      report on the purification of a multisubunit membrane-bound enzyme complex from
      A. fulgidus that contains a subunit related to the catalytic subunit of Hdr. The
      purified enzyme is a heme/iron-sulfur protein, as deduced by UV/Vis spectroscopy,
      EPR spectroscopy, and the primary structure. It is composed of four different
      subunits encoded by a putative transcription unit (AF499, AF501-AF503). A fifth
      protein (AF500) encoded by this transcription unit could not be detected in the
      purified enzyme preparation. Subunit AF502 is closely related to the catalytic
      subunit HdrD of Hdr from Methanosarcina barkeri. AF501 encodes a membrane
      integral cytochrome, and AF500 encodes a second integral membrane protein. AF499
      encodes an extracytoplasmic iron-sulfur protein, and AF503 encodes an
      extracytoplasmic c-type cytochrome with three heme c-binding motifs. All of the
      subunits show high sequence similarity to proteins encoded by the dsr locus of
      Allochromatium vinosum and to subunits of the Hmc complex from Desulfovibrio
      vulgaris. The heme groups of the enzyme are rapidly reduced by reduced 2,3
      dimethyl-1,4-naphthoquinone (DMNH2), which indicates that the enzyme functions as
      a menaquinol-acceptor oxidoreductase. The physiological electron acceptor has not
      yet been identified. Redox titrations monitored by EPR spectroscopy were carried
      out to characterize the iron-sulfur clusters of the enzyme. In addition to EPR
      signals due to [4Fe-4S]+ clusters, signals of an unusual paramagnetic species
      with g values of 2.031, 1.994, and 1.951 were obtained. The paramagnetic species
      could be reduced in a one-electron transfer reaction, but could not be further
      oxidized, and shows EPR properties similar to those of a paramagnetic species
      recently identified in Hdr. In Hdr this paramagnetic species is specifically
      induced by the substrates of the enzyme and is thought to be an intermediate of
      the catalytic cycle. Hence, Hdr and the A. fulgidus enzyme not only share
      sequence similarity, but may also have a similar active site and a similar
      catalytic function.

PMID- 11952792
TI  - The solution structure of reduced dimeric copper zinc superoxide dismutase. The
      structural effects of dimerization.
AB  - The solution structure of homodimeric Cu2Zn2 superoxide dismutase (SOD) of 306
      aminoacids was determined on a 13C, 15N and 70% 2H labeled sample. Two-thousand
      eight-hundred and five meaningful NOEs were used, of which 96 intersubunit, and
      115 dihedral angles provided a family of 30 conformers with an rmsd from the
      average of 0.78 +/- 0.11 and 1.15 +/- 0.09 A for the backbone and heavy atoms,
      respectively. When the rmsd is calculated for each subunit, the values drop to
      0.65 +/- 0.09 and 1.08 +/- 0.11 A for the backbone and heavy atoms, respectively.
      The two subunits are identical on the NMR time scale, at variance with the X-ray
      structures that show structural differences between the two subunits as well as
      between different molecules in the unit cell. The elements of secondary
      structure, i.e. eight beta sheets, are the same as in the X-ray structures and
      are well defined. The odd loops (I, III and V) are well resolved as well as loop
      II located at the subunit interface. On the contrary, loops IV and VI show some
      disorder. The residues of the active cavity are well defined whereas within the
      various subunits of the X-ray structure some are disordered or display different
      orientation in different X-ray structure determinations. The copper(I) ion and
      its ligands are well defined. This structure thus represents a well defined model
      in solution relevant for structure-function analysis of the protein. The
      comparison between the solution structure of monomeric mutants and the present
      structure shows that the subunit-subunit interactions increase the order in loop
      II. This has the consequences of inducing the structural and dynamic properties
      that are optimal for the enzymatic function of the wild-type enzyme. The regions
      37-43 and 89-95, constituting loops III and V and the initial part of the beta
      barrel and showing several mutations in familial amyotrophis lateral sclerosis
      (FALS)-related proteins have a quite extensive network of H-bonds that may
      account for their low mobility. Finally, the conformation of the key Arg143
      residue is compared to that in the other dimeric and monomeric structures as well
      as in the recently reported structure of the CCS-superoxide dismutase (SOD)
      complex.

PMID- 11952794
TI  - Characterization of isocitrate dehydrogenase from the green sulfur bacterium
      Chlorobium limicola. A carbon dioxide-fixing enzyme in the reductive
      tricarboxylic acid cycle.
AB  - Isocitrate dehydrogenase (IDH) catalyzes the reversible conversion between
      isocitrate and 2-oxoglutarate accompanied by decarboxylation/carboxylation and
      oxidoreduction of NAD(P)+ cofactor. While this enzyme has been well studied as a
      catabolic enzyme in the tricarboxylic acid (TCA) cycle, here we have
      characterized NADP-dependent IDH from Chlorobium limicola, a green sulfur
      bacterium that fixes CO2 through the reductive tricarboxylic acid (RTCA) cycle,
      focusing on the CO2-fixation ability of the enzyme. The gene encoding Cl-IDH
      consisted of 2226 bp, corresponding to a polypeptide of 742 amino acid residues.
      The primary structure and the size of the recombinant protein indicated that Cl
      IDH was a monomeric enzyme of 80 kDa distinct from the dimeric NADP-dependent
      IDHs predominantly found in bacteria or eukaryotic mitochondria. Apparent
      Michaelis constants for isocitrate (45 +/- 13 microm) and NADP+ (27 +/- 10
      microm) were much smaller than those for 2-oxoglutarate (1.1 +/- 0.5 mm) and CO2
      (1.3 +/- 0.3 mm). No significant differences in kinetic properties were observed
      between Cl-IDH and the dimeric, NADP-dependent IDH from Saccharomyces cerevisiae
      (Sc-IDH) at the optimum pH of each enzyme. However, in contrast to the 20%
      activity of Sc-IDH toward carboxylation as compared with that toward
      decarboxylation at pH 7.0, the activities of Cl-IDH for both directions were
      almost equivalent at this pH, suggesting a more favorable property of Cl-IDH than
      Sc-IDH as a CO2-fixation enzyme under physiological pH. Furthermore, we found
      that among various intermediates, oxaloacetate was a competitive inhibitor (K(i)
      = 0.35 +/- 0.04 mm) for 2-oxoglutarate in the carboxylation reaction by Cl-IDH, a
      feature not found in Sc-IDH.

PMID- 11952793
TI  - Inhibition of glyceraldehyde-3-phosphate dehydrogenase by peptide and protein
      peroxides generated by singlet oxygen attack.
AB  - Reaction of certain peptides and proteins with singlet oxygen (generated by
      visible light in the presence of rose bengal dye) yields long-lived peptide and
      protein peroxides. Incubation of these peroxides with glyceraldehyde-3-phosphate
      dehydrogenase, in the absence of added metal ions, results in loss of enzymatic
      activity. Comparative studies with a range of peroxides have shown that this
      inhibition is concentration, peroxide, and time dependent, with H2O2 less
      efficient than some peptide peroxides. Enzyme inhibition correlates with loss of
      both the peroxide and enzyme thiol residues, with a stoichiometry of two thiols
      lost per peroxide consumed. Blocking the thiol residues prevents reaction with
      the peroxide. This stoichiometry, the lack of metal-ion dependence, and the
      absence of electron paramagnetic resonance (EPR)-detectable species, is
      consistent with a molecular (nonradical) reaction between the active-site thiol
      of the enzyme and the peroxide. A number of low-molecular-mass compounds
      including thiols and ascorbate, but not Trolox C, can prevent inhibition by
      removing the initial peroxide, or species derived from it. In contrast,
      glutathione reductase and lactate dehydrogenase are poorly inhibited by these
      peroxides in the absence of added Fe2+-EDTA. The presence of this metal-ion
      complex enhanced the inhibition observed with these enzymes consistent with the
      occurrence of radical-mediated reactions. Overall, these studies demonstrate that
      singlet oxygen-mediated damage to an initial target protein can result in
      selective subsequent damage to other proteins, as evidenced by loss of enzymatic
      activity, via the formation and subsequent reactions of protein peroxides. These
      reactions may be important in the development of cellular dysfunction as a result
      of photo-oxidation.

PMID- 11952796
TI  - NMR investigations of subunit c of the ATP synthase from Propionigenium modestum
      in chloroform/methanol/water (4 : 4 : 1).
AB  - The subunit c from the ATP synthase of Propionigenium modestum was studied by NMR
      in chloroform/methanol/water (4 : 4 : 1). In this solvent, subunit c consists of
      two helical segments, comprised of residues L5 to I26 and G29 to N82,
      respectively. On comparing the secondary structure of subunit c from P. modestum
      in the organic solvent mixture with that in dodecylsulfate micelles several
      deviations became apparent: in the organic solvent, the interruption of the alpha
      helical structure within the conserved GXGXGXGX motif was shortened from five to
      two residues, the prominent interruption of the alpha helical structure in the
      cystoplasmic loop region was not apparent, and neither was there a break in the
      alpha helix after the sodium ion-binding Glu65 residue. The folding of subunit c
      of P. modestum in the organic solvent also deviated from that of Escherichia coli
      in the same environment, the most important difference being that subunit c of P.
      modestum did not adopt a stable hairpin structure like subunit c of E. coli.

PMID- 11952795
TI  - Functionally active fusion protein of the novel composite cytokine CLC/soluble
      CNTF receptor.
AB  - The heterodimeric cytokine composed of the soluble ciliary neurotrophic factor
      receptor (sCNTFR) and the IL-6 family member cardiotrophin-like cytokine (CLC)
      was recently identified as a new ligand for gp130-leukemia inhibitory factor
      receptor (LIFR) complex [Plun-Favreau, H., Elson, G., Chabbert, M., Froger, J.,
      deLapeyriere, O., Lelievre, E., Guillet, C., Hermann, J., Gauchat, J. F., Gascan,
      H. & Chevalier, S. (2001) EMBO J. 20, 1692-1703]. This heterodimer shows
      overlapping biological properties with LIF. Although CLC contains a putative
      signal peptide and therefore should enter into the classical secretory pathway,
      the protein has been shown to be retained within transfected mammalian cells,
      unless coexpressed with either sCNTFR or cytokine like factor (CLF) [Elson, G.
      C., Lelievre, E., Guillet, C., Chevalier, S., Plun-Favreau, H., Froger, J.,
      Suard, I., de Coignac, A. B., Delneste, Y., Bonnefoy, J. Y., Gauchat, J. F. &
      Gascan, H. (2000) Nat. Neurosci. 3, 867-872]. In the present study, we
      demonstrate that a fusion protein comprising CLC covalently coupled through a
      glycine/serine linker to sCNTFR (CC-FP) is efficiently secreted from transfected
      mammalian cells. CC-FP shows enhanced activities in respect to the CLC/sCNTFR
      native complex, on a number of cells expressing gp130 and LIFR on their surface.
      In addition, CC-FP is able to compete with CNTF for cell binding, indicating that
      both cytokines share binding epitope(s) expressed by their receptor complex.
      Analysis of the downstream signaling events revealed the recruitment by CC-FP of
      the signal transducer and activator of transcription (STAT)-3, Akt and mitogen
      activated protein (MAP) kinase pathways. The monomeric bioactive CLC/sCNTFR
      fusion protein is therefore a powerful tool to study the biological role of the
      recently described cytokine CLC.

PMID- 11952797
TI  - Molecular cloning of the Matrix Gla Protein gene from Xenopus laevis. Functional
      analysis of the promoter identifies a calcium sensitive region required for basal
      activity.
AB  - To analyze the regulation of Matrix Gla Protein (MGP) gene expression in Xenopus
      laevis, we cloned the xMGP gene and its 5' region, determined their molecular
      organization, and characterized the transcriptional properties of the core
      promoter. The Xenopus MGP (xMGP) gene is organized into five exons, one more as
      its mammalian counterparts. The first two exons in the Xenopus gene encode the
      DNA sequence that corresponds to the first exon in mammals whereas the last three
      exons show homologous organization in the Xenopus MGP gene and in the mammalian
      orthologs. We characterized the transcriptional regulation of the xMGP gene in
      transient transfections using Xenopus A6 cells. In our assay system the
      identified promoter was shown to be transcriptionally active, resulting in a 12
      fold induction of reporter gene expression. Deletional analysis of the 5' end of
      the xMGP promoter revealed a minimal activating element in the sequence from -70
      to -36 bp. Synthetic reporter constructs containing three copies of the defined
      regulatory element delivered 400-fold superactivation, demonstrating its
      potential for the recruitment of transcriptional activators. In gel mobility
      shift assays we demonstrate binding of X. laevis nuclear factors to an extended
      regulatory element from -180 to -36, the specificity of the interaction was
      proven in competition experiments using different fragments of the xMGP promoter.
      By this approach the major site of factor binding was demonstrated to be included
      in the minimal activating promoter fragment from -70 to -36 bp. In addition, in
      transient transfection experiments we could show that this element mediates
      calcium dependent transcription and increasing concentrations of extracellular
      calcium lead to a significant dose dependent activation of reporter gene
      expression.

PMID- 11952799
TI  - Infrared spectroscopy as a tool for discrimination between sensitive and
      multiresistant K562 cells.
AB  - Fourier transform infrared spectroscopy was performed on human leukemic
      daunorubicin-sensitive K562 cells and their multiresistant counterpart derived by
      selection. Statistical analysis, including variable reduction and linear
      discriminant analysis was performed on sensitive and multiresistant cells spectra
      in order to establish a diagnostic tool for multiresistant pattern. For each of
      the two methods of data reduction tested [genetic algorithm or principal
      component analysis (PCA)] discrimination between the two cell lines was found to
      be possible. The best results, obtained with PCA-reduction, showed an accuracy of
      93% on a distinct test set of spectra. These results demonstrate the efficiency
      of Fourier transform infrared spectroscopy for classification. Further analysis
      of the spectral differences indicated that discrimination between resistant and
      sensitive cells was based on variations in all cellular contents. Lipid and
      nucleic acid decreased, relatively, while the protein content increased.

PMID- 11952798
TI  - Molecular characterization of a novel nuclear transglutaminase that is expressed
      during starfish embryogenesis.
AB  - We report the constitution and molecular characterization of a novel
      transglutaminase (EC 2.3.2.13) that starts to accumulate specifically in the
      nucleus in the starfish (Asterina pectinifera) embryo after progression through
      the early blastula stage. The cDNA for the nuclear transglutaminase was cloned
      and the cDNA-deduced sequence defines a single open reading frame encoding a
      protein with 737 amino acids and a predicted molecular mass of 83 kDa. A
      comparison of this transglutaminase with other members of the gene family
      revealed an overall sequence identity of 33-41%. A special sequence feature of
      this transglutaminase, which is not found in other transglutaminases, is the
      presence of nuclear localization signal-like sequences in the N-terminal region.
      Microinjection of hybrid constructs that encode the N-terminal segment fused to
      reporter proteins into the germinal vesicle of an oocyte produced chimeric
      proteins by transcription-coupled translation. It was found that the N-terminal
      segment alone was sufficient to effect nuclear accumulation of an otherwise
      cytoplasmic protein. These results suggest that the nuclear accumulation of the
      transglutaminase may play an important role in nuclear remodeling during early
      starfish embryogenesis.

PMID- 11952800
TI  - Reconstitution of coupled fumarate respiration in liposomes by incorporating the
      electron transport enzymes isolated from Wolinella succinogenes.
AB  - Hydrogenase and fumarate reductase isolated from Wolinella succinogenes were
      incorporated into liposomes containing menaquinone. The two enzymes were found to
      be oriented solely to the outside of the resulting proteoliposomes. The
      proteoliposomes catalyzed fumarate reduction by H2 which generated an electrical
      proton potential (Delta(psi) = 0.19 V, negative inside) in the same direction as
      that generated by fumarate respiration in cells of W. succinogenes. The H+/e
      ratio brought about by fumarate reduction with H2 in proteoliposomes in the
      presence of valinomycin and external K+ was approximately 1. The same Delta(psi)
      and H+/e ratio was associated with the reduction of 2,3-dimethyl-1,4
      naphthoquinone (DMN) by H2 in proteoliposomes containing menaquinone and
      hydrogenase with or without fumarate reductase. Proteoliposomes containing
      menaquinone and fumarate reductase with or without hydrogenase catalyzed fumarate
      reduction by DMNH2 which did not generate a Delta(psi). Incorporation of formate
      dehydrogenase together with fumarate reductase and menaquinone resulted in
      proteoliposomes catalyzing the reduction of fumarate or DMN by formate. Both
      reactions generated a Delta(psi) of 0.13 V (negative inside). The H+/e ratio of
      formate oxidation by menaquinone or DMN was close to 1. The results demonstrate
      for the first time that coupled fumarate respiration can be restored in liposomes
      using the well characterized electron transport enzymes isolated from W.
      succinogenes. The results support the view that Delta(psi) generation is coupled
      to menaquinone reduction by H2 or formate, but not to menaquinol oxidation by
      fumarate. Delta(psi) generation is probably caused by proton uptake from the
      cytoplasmic side of the membrane during menaquinone reduction, and by the coupled
      release of protons from H2 or formate oxidation on the periplasmic side. This
      mechanism is supported by the properties of two hydrogenase mutants of W.
      succinogenes which indicate that the site of quinone reduction is close to the
      cytoplasmic surface of the membrane.

PMID- 11952801
TI  - A point mutation in the ATP synthase of Rhodobacter capsulatus results in
      differential contributions of Delta(pH) and Delta(phi) in driving the ATP
      synthesis reaction.
AB  - The interface between the c-subunit oligomer and the a subunit in the F0 sector
      of the ATP synthase is believed to form the core of the rotating motor powered by
      the protonic flow. Besides the essential cAsp61 and aArg210 residues (Escherichia
      coli numbering), a few other residues at this interface, although nonessential,
      show a high degree of conservation, among these aGlu219. The homologous residue
      aGlu210 in the ATP synthase of the photosynthetic bacterium Rhodobacter
      capsulatus has been substituted by a lysine. Inner membranes prepared from the
      mutant strain showed approximately half of the ATP synthesis activity when driven
      both by light and by acid-base transitions. As estimated with the ACMA assay,
      proton pumping rates in the inner membranes were also reduced to a similar extent
      in the mutant. The most striking impairment of ATP synthesis in the mutant, a
      decrease as low as 12 times as compared to the wild-type, was observed in the
      absence of a transmembrane electrical membrane potential (Delta(phi)) at low
      transmembrane pH difference (Delta(pH)). Therefore, the mutation seems to affect
      both the mechanism responsible for coupling F1 with proton translocation by F0,
      and the mechanism determining the relative contribution of Delta(pH) and
      Delta(phi) in driving ATP synthesis.

PMID- 11952803
TI  - Correlation between heavy alcohol consumption and elevation of matrix
      metalloproteinases.

PMID- 11952804
TI  - Histamine is a multicoloured player in many physiological functions; it has a
      significant role in regulation of white adipose tissue and food intake.

PMID- 11952805
TI  - HDL or not HDL, that is the question.

PMID- 11952806
TI  - Matrix metalloproteinase-9 is elevated in serum of alcohol abusers.
AB  - BACKGROUND: Moderate alcohol consumption has been shown to protect against
      coronary heart disease. However, excessive alcohol use has been suggested to have
      detrimental effects on the cardiovascular system. We examined whether there is an
      association between alcohol abuse and circulating levels of matrix
      metalloproteinase-9 (MMP-9), which has been linked to unstable coronary heart
      disease and arterial inflammation. DESIGN: Serum MMP-9 concentrations were
      compared between 40 male alcoholics (mean age 42 years) with ethanol consumption
      > 1000 g week(-1) and 40 social drinker males with an ethanol consumption of <
      200 g week(-1) (mean age 45 years). RESULTS: The mean serum MMP-9 concentration
      was significantly higher in sera of alcoholics compared to control subjects (70.9
      +/- 47.7 g L(-1) and 43.1 +/- 19.2 g L(-1), respectively; P = 0.001). Within the
      alcoholic group, MMP-9 concentration did not correlate with age, gamma glutamyl
      transferase, carbohydrate-deficient transferrin, aspartate aminotransferase,
      alanine aminotransferase or alkaline phosphatase. CONCLUSION: Our finding of
      elevated MMP-9 concentrations in sera of chronic alcohol abusers helps understand
      the mechanisms of cardiovascular risk among these subjects.

PMID- 11952807
TI  - Endothelin ETA receptor-subtype specific antagonism does not mitigate the acute
      systemic or renal effects of exogenous angiotensin II in humans.
AB  - BACKGROUND: Angiotensin II (Ang II) is assumed to play a pathophysiological role
      in a variety of vascular diseases. Animal studies indicate that these effects are
      partly attributed to stimulation of endothelin-1 (ET-1) release. The aim of the
      present study was to investigate whether the acute effects of Ang II on systemic
      and renal haemodynamics in healthy subjects can be influenced by endothelin ET(A)
      receptor blockade. DESIGN: The study design was balanced, randomized, placebo
      controlled, double blind, two-way cross-over, in 10 healthy male subjects.
      METHODS: Subjects received stepwise increasing intravenous doses of Ang II (0.65,
      1.25, 2.5, 5 ng kg(-1) min(-1) for 15 min per dose level) in the presence or
      absence of BQ-123 (60 microg min(-1)), a specific ETA-receptor antagonist. Renal
      plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by the para
      aminohippurate and inulin plasma clearance method, respectively. Renal vascular
      resistance (RVR) was calculated from mean arterial pressure (MAP) and renal
      plasma flow. RESULTS: Ang II decreased RPF by 34% and GFR by 9% and increased RVR
      by 94% and MAP by 27% (ANOVA, P < 0.001 vs. baseline, for all parameters). BQ-123
      did not alter these renal and systemic haemodynamic responses to a significant
      degree. In addition, BQ-123 had no significant haemodynamic effect under baseline
      conditions. CONCLUSIONS: Short-term increase of circulating Ang II levels causes
      systemic and renal pressor effects, which are not mitigated by endothelin ETA
      receptor blockade. This suggests that the pressor response to Ang II cannot be
      accounted for by the acute release of vasoactive ET-1.

PMID- 11952808
TI  - Histidine induces lipolysis through sympathetic nerve in white adipose tissue.
AB  - BACKGROUND: Hypothalamic neuronal histamine has been shown to increase lipolysis
      in white adipose tissue. The present study aimed to clarify whether peripheral
      loading with L-histidine, a precursor of neuronal histamine, may affect lipid
      metabolism in adipose tissue. MATERIALS AND METHODS: The in vivo microdialysis
      study was used to assess lipolysis in rat epididymal adipose tissue by measuring
      the release of glycerol in response to administration of L-histidine. In
      addition, electrophysiological measurements were performed to record changes in
      activity of sympathetic nerve innervating adipose tissue following histidine
      treatment. RESULTS: Sequential administration of isoproterenol, a beta
      adrenoceptor agonist, through the microdialysis cannula at concentrations of 10(
      )8 to 10(-6) M increased the glycerol concentration in the dialysate dose
      dependently (P < 0.05). Intraperitoneal administration of L-histidine at a dosage
      of 0.35 mmol kg(-1) also increased the glycerol concentration compared to that of
      phosphate buffered saline (P < 0.05). Concomitantly, the administration of
      histidine increased the serum concentration of free fatty acid compared to
      control treatment (P < 0.05). The accelerating effects of histidine on lipolysis
      were mimicked by the infusion of 10(2) nmol rat(-1) L-histamine into the third
      cerebroventricle (P < 0.05). Electrophysiological measurement demonstrated that
      administration of histidine at a dosage of 0.35 mmol kg(-1) increased the
      activity of efferent sympathetic nerve, innervating adipose tissue more than the
      infusion of phosphate buffered saline (P < 0.05). CONCLUSION: The present results
      indicate that histidine accelerates lipolysis in white adipose tissue through
      activation of the sympathetic nerve. The regulation of lipolysis may therefore
      involve histamine neurons in the brain, probably through the conversion of L
      histidine to histamine in the hypothalamus.

PMID- 11952810
TI  - Influence of apolipoprotein E polymorphism on plasma vitamin A and vitamin E
      levels.
AB  - BACKGROUND: Plasma concentrations of vitamins A and E are positively correlated
      with those of concurrent lipids and, on the other hand, lipid levels are
      influenced by apolipoprotein E polymorphism. Therefore, the effect of this
      polymorphism on both vitamins was analysed in an adult population. MATERIALS AND
      METHODS: Subjects were recruited from a working population. Their anthropometric,
      lifestyle and dietary intake variables and menopausal status were recorded. Their
      apolipoprotein E phenotype and their plasma vitamins A and E (by high-performance
      liquid chromatography) and lipid (enzymatically) concentrations were determined
      after an overnight fast. The associations of the phenotype with vitamins and
      lipids were studied in men and women separately and controlling for significant
      covariates. RESULTS: The apolipoprotein E phenotype was associated with the
      concentrations of total, low-density lipoprotein (LDL) and high-density
      lipoprotein (HDL) cholesterol in women, whereas no associations with lipids were
      found in men. Vitamin A and vitamin E levels were higher in men than in women,
      but only the difference in the former persisted after lipid adjustment.
      Apolipoprotein E2 slightly increased vitamin A levels in women, an effect which
      was still evident with lipid adjustment. Actually, both the apolipoprotein E
      phenotype and triglyceride were selected as significant predictors of this
      vitamin by multiple regression. This phenotype did not affect vitamin E levels in
      either sex. CONCLUSIONS: Lipids do not mediate the effect of gender on vitamin A
      levels. Apolipoprotein E polymorphism is an independent determinant of vitamin A
      levels in women. Pending confirmation by others, we propose that enhancement of
      this vitamin may contribute to the beneficial impact of the epsilon2 allele on
      human ageing and health.

PMID- 11952809
TI  - Relationship of genetic variation in genes encoding apolipoprotein A-IV,
      scavenger receptor BI, HMG-CoA reductase, CETP and apolipoprotein E with
      cholesterol metabolism and the response to plant stanol ester consumption.
AB  - BACKGROUND: Differences in genetic constitution may affect cholesterol metabolism
      and responses to diet. Identification of common variations in genes related to
      dietary responsiveness is therefore an attractive goal to be able to prescribe
      individually tailored diets for the treatment of dyslipidaemia. MATERIALS AND
      METHODS: We have examined relationships between serum lipids and lipoproteins,
      cholesterol-standardized campesterol and lathosterol concentrations with genetic
      variation, and the presence of a gene-diet interaction between plant stanol ester
      consumption. Candidate genes were apolipoprotein A-IV (apoA-IV), scavenger
      receptor-BI (SR-BI), cholesterol ester transfer protein (CETP), 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase, and apolipoprotein E (apoE). These
      relations were examined in 112 nonhypercholesterolaemic subjects, of whom 70
      consumed 3.8-4.0 g plant stanol esters a day for 8 weeks. RESULTS: At baseline,
      high-density lipoprotein (HDL) concentrations of 1.56 +/- 0.36 mmol L(-1) in SR
      BI-2 allele carriers tended to be lower compared to the 1.72 +/- 0.42 mmol L(-1)
      in SR-BI-1/1 subjects (P = 0.069). Cholesterol standardized lathosterol
      concentrations were also lower in the SR-BI-2 allele carriers (P = 0.002).
      Furthermore, low-density lipoprotein (LDL) cholesterol concentrations in apoE2
      subjects, were lower compared to the LDL cholesterol concentration in apoE3 group
      (P = 0.002) and apoE4 subjects (P < 0.001). No significant differences between
      the polymorphisms and dietary responsiveness to plant stanol ester consumption
      could be found, which indicates that it is unlikely that one of the single
      polymorphisms analysed in this study is a major factor in explaining the
      variation in serum LDL cholesterol responses. CONCLUSION: These findings suggest
      that all subjects who want to lower their cholesterol concentration, will benefit
      from plant stanol ester consumption, irrespective of their apoA-IV, SR-BI, HMG
      CoA reductase, CETP, or apoE genotype.

PMID- 11952811
TI  - Serum paraoxonase activity in patients with type 1 diabetes compared to healthy
      controls.
AB  - BACKGROUND: The oxidation of low-density lipoprotein (LDL) is central to current
      theories on the initiation and progression of atherosclerosis. Type 1 diabetes is
      associated with an increase in oxidative stress, which may be responsible for the
      increased susceptibility to coronary heart disease seen in type 1 diabetes. High
      density lipoprotein (HDL) associated paraoxonase (PON1) can retard the oxidation
      of LDL. DESIGN: Paraoxonase activity, concentration and genotype were therefore
      investigated in 152 people with type 1 diabetes and 282 healthy controls. These
      parameters were also investigated in the group with type 1 diabetes in relation
      to the presence of diabetic complications. RESULTS: Both PON1 activity and
      concentration were significantly lower by 16.7% and 19.2% (both P < 0.05) in the
      type 1 diabetes group. These differences were independent of the PON1 coding
      region polymorphisms. The distribution of PON1 activity and mass were the same in
      both populations, i.e. for the PON1-192 polymorphism RR > RQ > QQ and for the
      PON1-55 polymorphism LL > LM > MM. There were no differences in either the PON1
      polymorphisms, PON1 activity and concentration in people with type 1 diabetes in
      the presence or absence of micro and macro vascular complications of diabetes.
      CONCLUSIONS: Low PON1 activity may contribute to the increased atherosclerosis
      found in type 1 diabetes by reducing the ability of HDL to retard LDL oxidation
      despite the frequently-found increased HDL in type 1 diabetes when good glycaemic
      control is established.

PMID- 11952812
TI  - Depletion of non specific esterase activity in the colonic mucosa of patients
      with ulcerative colitis.
AB  - BACKGROUND: Non specific esterases (NSE) are a group of cellular
      carboxylesterases, enzyme markers of monocytes/macrophages, whose tissue
      distribution in the human body and changes in various disease states have not
      been adequately studied. We investigate the presence and localization of NSE, in
      the normal and inflamed human colonic mucosa. DESIGN: NSE were studied
      histochemically and biochemically using alpha-naphthyl acetate as the substrate,
      in the colonic mucosa from 67 patients with colitis of various aetiologies and 10
      normal controls. In addition, esterase activity was studied biochemically in
      serum from colitic patients and normal controls. RESULTS: Histochemical study of
      the colonic tissue demonstrated that NSE were localised in the epithelial brush
      border, the goblet cells of the glands and a macrophage population of the lamina
      propria in the colonic mucosa of normal controls and patients with non specific
      colitis. In active ulcerative colitis, esterase depletion and esterase negative
      macrophages were identified in parallel with goblet cell disappearance. Gradual
      reappearance of esterase activity was found after successful treatment.
      Biochemical study of NSE activity showed that serum and colonic tissue esterase
      levels were greatly (P < 0.001) reduced in active ulcerative colitis compared to
      the normal controls or non specific colitis patients and they were increased
      after successful treatment. Despite this increase, the esterase activity in the
      colonic tissue from ulcerative colitis patients after treatment was significantly
      reduced compared to the normal controls. Interestingly, the enzyme levels from
      non-inflamed areas of the bowel of patients with ulcerative colitis were also
      significantly (P < 0.01) decreased compared to the normal controls. CONCLUSIONS:
      These data suggest that esterase reduction in ulcerative colitis is not a simple
      result of the inflammatory process but rather it precedes its development. This
      enzyme depletion might have an important pathogenetic implication in the
      inflammatory process.

PMID- 11952813
TI  - Can a determination of tartrate-resistant acid phosphatase predict postmenopausal
      loss of bone mass?
AB  - BACKGROUND: A study was carried out over a 24-month interval to determine if an
      initial measurement of serum tartrate-resistant acid phosphatase would be
      predictive of bone mass loss quantified by dual-energy X-ray absorptiometry, as
      total bone mineral content and total bone mineral content corrected for weight.
      DESIGN: Sixty-two women were studied (at onset: mean age 59.7 +/- 8.9 years, 10.8
      +/- 8.8 years since menopause; at conclusion: mean age 61.9 +/- 8.8 and 13.0 +/-
      8.7 since menopause). RESULTS: A paired Wilcoxon test showed a small, but
      significant, increase in weight (P < 0.05) and decrease in height (P < 0.05).
      Total bone mineral content and total bone mineral content corrected for weight
      decreased (P < 0.005 and 0.0001, respectively). Serum tartrate-resistant acid
      phosphatase increased (P < 0.005). Single-regression analysis showed that the per
      cent bone mass loss observed between the first and second body bone mineral
      content measurements correlated negatively with the first serum tartrate
      resistant acid phosphatase determination (r = -0.62, P < 0.0001). Changes in
      tartrate-resistant acid phosphatase correlated negatively with changes in total
      bone mineral content (r = -0.79, P < 0.0001). In a multiple regression analysis
      of per cent change in bone mass against initially important variables such as
      age, years since menopause, weight, and tartrate-resistant acid phosphatase, only
      tartrate-resistant acid phosphatase was significant (P < 0.0001). The sensitivity
      and specifity of tartrate-resistant acid phosphatase for evaluating bone loss
      were 86% and 78%, respectively, and the area under the curve was of 0.83 (95% CI
      0.71-0.95). CONCLUSION: These results show that a simple measurement of serum
      tartrate-resistant acid phosphatase can help to predict the potential rate of
      bone mass loss in women.

PMID- 11952814
TI  - Effect of homocysteine on arachidonic acid release in human platelets.
AB  - BACKGROUND: It has been suggested that homocysteine is implicated in the risk of
      atherosclerosis and thrombosis. The pathogenic mechanism has not been clarified,
      but oxygen-free species produced by the homocysteine metabolism and auto
      oxidation could have a role. DESIGN: We have studied the effect of homocysteine
      on arachidonic acid release in human platelets. Two important products of
      arachidonic acid metabolism - thromboxane B2 (TXB2) and reactive oxygen species
      (ROS) - have been assayed. RESULTS: Results indicate that homocysteine induces
      arachidonic acid release that is partially inhibited by 5,8,11,14
      eicosatetraynoic acid (ETYA). Platelet incubation with homocysteine significantly
      increases basal levels of TXB2 and ROS. The effect is time- and dose-dependent.
      The TXB2 formation is strictly correlated with the arachidonic acid release.
      Moreover, ROS accumulation is largely inhibited by ETYA and partially reduced by
      diphenyleneiodonium (DPI), suggesting the involvement both of enzymes
      metabolising arachidonic acid (cyclooxygenase, lipooxygenase, cytochrome P450
      monooxygenase) and of NAD(P)H oxidase. CONCLUSION: Homocysteine induces oxidative
      stress in human platelets in vitro. The unbalance in platelet redox-state and the
      increased TXB2 formation may generate hyperactivation, contributing to a
      thrombogenic state leading to cardiovascular diseases.

PMID- 11952815
TI  - Saturated triglycerides and fatty acids activate neutrophils depending on carbon
      chain-length.
AB  - BACKGROUND: Unsaturated fatty acids are known as neutrophil activators. In the
      present study we investigated whether saturated triglycerides and fatty acids may
      also contribute to the previously observed activation of neutrophils by
      nutritional lipid emulsions. Furthermore we tested the hypothesis that carbon
      chain length is of importance in this respect. MATERIALS AND METHODS: Neutrophils
      (1 x 10(6) mL(-1)) were isolated from the blood of nine volunteers.
      Chemiluminescence was used to evaluate neutrophil activation, characterized by
      the production of oxygen radicals by neutrophils during incubation with 1 mmol L(
      1) saturated fatty acid (6-20 carbon) or triglycerides (6-12 carbon fatty acid),
      dissolved in aqueous medium by preparing micelles with dipalmitoyl
      phosphatidylcholine (DPPC). Results were expressed as means +/- SEMs of the
      overall luminescence signal relative to the signal of cells incubated in medium.
      RESULTS: Similar to a positive control, the polyunsaturated fatty acid
      arachidonic acid (C20 : 4), the triglycerides tricaproin (TC6 : 0), tricaprylin
      (TC8 : 0) and trilaurin (TC12 : 0) as well as the fatty acids lauric acid (C12 :
      0), palmitic acid (C16 : 0), stearic acid (C18 : 0) and arachidic acid (C20 : 0)
      all induced oxygen radical production in neutrophils, while the medium-chain
      triglyceride tricaprin (TC10 : 0) and fatty acids caproic acid (C6 : 0), caprylic
      acid (C8 : 0) and capric acid (C10 : 0) exerted no clear effects, similar to
      negative controls (DPPC and glycerol). CONCLUSIONS: Besides their (poly)
      unsaturated counterparts, saturated triglycerides and fatty acids also activate
      neutrophils. Carbon chain-length is pivotal in the interaction of fatty acids and
      triglycerides and cells of the immune system.

PMID- 11952816
TI  - Cutaneous pleomorphic T-cell lymphoma coexisting with myelodysplastic syndrome
      transforming into acute myeloid leukemia: successful treatment with a fludarabine
      containing regimen.
AB  - The coexistence of a primary myelodysplastic syndrome (MDS) and a T-cell
      cutaneous non-Hodgkin's lymphoma is an extremely rare event, which has so far
      only been reported in a single instance in the literature. We describe herein an
      additional case in which the lymphoid disease was combined with an MDS at the
      time of its evolution into acute myeloid leukemia (AML). Both diseases were
      successfully treated with a regimen containing fludarabine. We discuss possible
      pathogenetic mechanisms and suggest the use of nonalkylating drugs, such as
      fludarabine, for the treatment of this rare association of malignancies usually
      characterized by a very poor response to therapy.

PMID- 11952817
TI  - The splenic form of mantle cell lymphoma.
AB  - OBJECTIVES: To describe the clinical, immunophenotypic and molecular features, as
      well as the clinical course of patients with unusual presentation of mantle cell
      lymphoma (MCL) purely located to the spleen. PATIENTS AND METHODS: We describe
      seven patients presented with splenomegaly and a leukemic picture without
      lymphadenopathy, fulfilling the diagnostic criteria of MCL. In addition to
      clinical and pathologic features, patients were studied with respect to surface
      immunophenotype, including adhesion molecule profile, immunohistochemical
      expression of cyclin-D1 and bcl-1 rearrangement by polymerase chain reaction.
      RESULTS: Four patients were male and three female. The median palpable spleen
      size was 15 cm. A preliminary diagnosis of MCL was made, based on blood cell
      morphology and immunophenotype. All patients underwent splenectomy for
      therapeutic purposes. Studies done in blood and splenic lymphocytes revealed the
      following: 7/7 patients were CD19/CD5, CD20 and CD38 positive; CD10 negative and
      6/7 CD23 negative. The adhesion molecule expression pattern was consistent in all
      patients: L-Selectin and CD11c were negative, CD11alpha and CD18 weakly positive
      and CD54 strongly positive. The median spleen weight was 1775 g. Histology
      disclosed a cytologic and architectural pattern consistent with MCL. Cyclin-D1
      was positive in 6/6 studied patients. Bcl-1 rearrangement was found in 5/7
      patients. Splenectomy was applied as the sole treatment and was beneficial in all
      patients, with median blood values as following: prior to splenectomy, Ht 29.5%,
      platelets 110 x 10(9)/l, lymphoma cells 5.0 x 10(9)/L, and at 6 months post
      splenectomy, Ht 43%, platelets 311 x 10(9)/l and lymphoma cells 3.0 x 10(9)/L. Of
      the seven patients, two developed progressive disease 11 and 26 months post
      splenectomy. The remaining five are in improving clinical and hematological
      condition without chemotherapy at a median follow up of 20 months. CONCLUSIONS:
      We conclude that this presentation represents a separate form of MCL which
      requires splenectomy. It remains to be seen whether it carries a better prognosis
      than classical MCL.

PMID- 11952818
TI  - Hyposialated 185 kDa CD45RA+ molecules attain a high concentration in B lymphoma
      cells and in activated human B cells.
AB  - Alternate splicing of exons of the CD45 molecule generates multiple isoforms
      differing in their molecular weights (MWs). In B-lymphocytes the CD45RA isoform
      was previously shown to be expressed on glycoproteins with MWs of 220 and 205
      kDa, while the CD45RO isoform was expressed on glycoproteins with MW of 180 kDa.
      The present study demonstrated that B cell lymphomas and activated B-cells
      contain CD45 molecules with a MW of 185 kDa that express the CD45RA and CD45RC
      specificities but neither the CD45RB nor the CD45RO specificities. 185 kDa
      CD45RA+ molecules were detected in B cell lymphoma B lines, in Epstein-Barr virus
      (EBV)-transformed lymphoblastoid cell lines, and in tonsillar B cells, but not in
      normal, unstimulated peripheral blood B cells. These molecules were not detected
      in neoplastic and normal T cells. CD45RA+ 185 kDa molecules were present in B
      cells from three non-Hodgkin's patients in leukemic phase were not detected in B
      lymphocytes of seven of nine CLL patients tested. Trypsin treatment eliminated
      only 220 kDa CD45RA+ molecules but not 185 kDa CD45RA+ molecules, indicating that
      the 185 kDa CD45RA+ molecules are not expressed on the cell surface. Pulse-chase
      experiments, and studies on the effects of tunicamycin, neuraminidase and O
      glycosidase, indicated that the 185 kDa molecules are partially glycosylated
      CD45RABC molecules that constitute precursors of the 220 kDa molecules. The high
      concentration of 185 kDa CD45RA+ molecules in B lymphoma cells and in activated B
      cells seems to reflect a high turnover of CD45RA+ molecules characteristic for
      these cells.

PMID- 11952819
TI  - Spectral karyotyping and interphase FISH reveal abnormalities not detected by
      conventional G-banding. Implications for treatment stratification of childhood
      acute lymphoblastic leukaemia: detailed analysis of 70 cases.
AB  - Seventy uniformly treated children with acute lymphoblastic leukemia were
      analysed for chromosomal abnormalities with conventional G-banding, spectral
      karyotyping (SKY) and interphase fluorescent in situ hybridisation (FISH) using
      probes to detect MLL, BCR/ABL, TEL/AML1 rearrangements and INK4 locus deletions.
      Numerical and/or structural changes could be identified in 80% of the patients by
      the use of molecular cytogenetic techniques, whereas abnormalities could be
      detected in 60% of the patients using G-banding alone. Altogether, 106 structural
      aberrations were defined by FISH compared to 34 using G-banding. Seventy-four
      percent of the patients had numerical aberrations, 54% structural aberrations and
      20% had no identified aberrations. Twelve cases had prognostically unfavourable
      chromosomal aberrations that had not been detected in the G-banded analysis. We
      identified three novel TEL partner breakpoints on 1q41, 8q24 and 21p12, and a
      recurrent translocation t(1;12)(p32;p13) was found. In addition, two cases
      displayed amplification (7-15 copies) of AML1. Our results demonstrate the
      usefulness of SKY and interphase FISH for the identification of novel chromosome
      aberrations and cytogenetic abnormalities that provide prognostically important
      information in childhood ALL.

PMID- 11952820
TI  - Cancer-related anemia in a rat model: alpha2-macroglobulin from Yoshida sarcoma
      shortens erythrocyte survival.
AB  - Implantation of Yoshida ascites sarcoma in rats was found to lead to a reduction
      in the hemoglobin content, the erythrocyte count and the packed cell volume of
      blood to 30% of normal in 4 d; however, there was no decrease in the mean cell
      hemoglobin, the mean cell volume and the mean corpuscular hemoglobin
      concentration, or suppression of erythropoiesis. The red cells from the
      circulation of tumor-bearing animals, tagged with (51)Cr and injected
      intravenously in normal rats, showed significantly faster clearance than normal.
      The erythrocytes contaminating the tumor ascites exhibited extremely short
      survival, suggesting that one or more secreted tumor product(s) may be
      responsible for the effect. Incubation of red cells from normal rats in the cell
      free ascites fluid, or with an isoform of alpha2-macroglobulin purified from it,
      also led to reduction in the survival; but the ascites fluid depleted
      specifically of alpha2-macroglobulin was without any effect. The erythrocytes
      exhibiting reduced survival showed a proportionate decrease in their cellular
      deformability. The study identifies a tumor product that is directly responsible
      for the causation of anemia in the host, and the mechanism by which it does so.

PMID- 11952821
TI  - Steroid-refractory chronic idiopathic thrombocytopenic purpura associated with
      hepatitis C virus infection.
AB  - OBJECTIVES: Hepatitis C virus infection has often been suggested as a possible
      cause of various kinds of autoimmune diseases. The aim of this study was to
      determine the relationship between chronic idiopathic thrombocytopenic purpura
      (ITP) and hepatitis C virus infection and to characterize the clinical features
      of anti-HCV antibody (HCVab) positive chronic ITP patients. SUBJECTS AND METHODS:
      We studied HCVab in 79 patients with chronic ITP (25 males, 54 females, mean age
      42.3 yr, range 11-86 yr) using the third-generation ELISA method. RESULTS: HCVab
      was detected in 11 of the 79 patients (13.9%). Quantitative HCV-RNA studies
      showed a high serum concentration of HCV-RNA in these patients. The platelet
      counts in these 11 HCVab-positive patients (Group 1) were lower than in the 68
      HCVab-negative patients (Group 2) [(2.6 +/- 0.9) versus (4.9 +/- 3.0) x 10(10)/L,
      respectively; p<0.02]. Significantly more patients in Group 1 required
      prednisolone therapy (10/11, 90.9%) than in Group 2 (31/68, 45.6%) (P < 0.005).
      The response rate to prednisolone treatment was significantly higher in Group 2
      (19/31, 61.3%) than in Group 1(0/10, 0%) (P < 0.001). There was no difference in
      the response to splenectomy between Groups 1 (4/7, 57.1%) and 2 (3/5, 60%).
      CONCLUSION: Given these findings, we recommend that HCVab is measured upon
      diagnosis of chronic ITP, and that splenectomy is planned in patients with HCVab
      in the event that prednisolone treatment is ineffective.

PMID- 11952822
TI  - Improved outcome in adult acute myeloid leukemia is almost entirely restricted to
      young patients and associated with stem cell transplantation.
AB  - Prognostic factors were studied in a series of 318 patients with acute myeloid
      leukemia (AML), 17-90 yr old, treated at a single centre during 1982-98, and
      representing 79% of the total number of cases registered in the area during this
      period. Risk group stratification based on cytogenetics, occurrence of antecedent
      hematological disorder, and leukocyte count could be performed in 93%. Five
      percent were allocated to the favourable risk group, 40% to standard risk, and
      55% to adverse risk. Complete remission (CR) was attained in 52%. The CR rate was
      higher in the favourable (80%) and standard risk groups (69%) than in the adverse
      risk group (37%). The CR rate increased from 44% in the 1980s to 60% in the
      1990s. The 5-yr survival rate for all patients was only 12%. Low age,
      promyelocytic leukaemia, treatment in the 1990s, high induction treatment
      intensity, and non-adverse risk group were favourably associated with survival.
      The median survival time increased from 115 to 349 d between the 1980s and the
      1990s, but the 5-yr survival rate was only 11% for patients over 55 yr of age
      even in the last decade. For the younger patients, the 5-yr overall survival rate
      increased from 9% to 35% in the last decade. The median time in first remission
      was 365 d. Age below 56 yr, allogeneic and autologous transplants, and non
      adverse risk group were associated with prolonged response duration. The duration
      of response among all patients increased from 250 d in the 1980s to 451 d in the
      1990s, but event-free survival time did not improve significantly in patients
      above 55 yr of age. Among patients below 56 yr of age, overall survival and event
      free survival were significantly better for those who received allogeneic or
      autologous transplants in first remission than for those who were treated with
      chemotherapy only. Overall survival times did not improve from the 1980s to the
      1990s among those patients below 56 yr who were treated with chemotherapy only in
      first remission, in spite of the use of transplants in second remission.

PMID- 11952823
TI  - 'Activation-induced cell death': a special program able to preserve the
      homeostasis of the skin?
AB  - The 'activation-induced cell death' (AICD) is a molecular system leading to death
      of antigen-activated T lymphocytes, in order to avoid accumulation of harmful
      cytokine-releasing cells. This article reviews both the molecular mechanisms
      working in AICD and the role played by such mechanisms in preventing a number of
      skin diseases. Specifically, because AICD removes activated and autoreactive T
      cells through a CD95-/CD95-L-mediated suicide, skin diseases were scrutinized in
      which such valuable machinery could be lacking. Indeed, at least some
      inflammatory skin diseases, including psoriasis and atopic dermatitis, can be
      sustained by an increased survival of activated T lymphocytes associated with
      deficient CD95-/CD95-L-mediated AICD of such strong pro-inflammatory cells. In
      addition, autoreactive skin diseases, including, e.g. alopecia areata, lichen
      planus and other lichenoid tissue reactions, can be related to autoreactive T
      lymphocytes which could be unable to undergo CD95-/CD95-L-mediated AICD. Finally,
      a lack of AICD may be executive even in favoring cutaneous T cell lymphoma. Thus,
      because inflammatory, autoreactive and neoplastic skin diseases can be associated
      with a deficient CD95-/CD95-L-mediated suicide of activated T cells, AICD is
      likely to represent a fundamental program to preserve the homeostasis of the
      skin. Therapeutic approaches able to restore the AICD machinery promise to
      successfully treat such relevant skin diseases.

PMID- 11952824
TI  - Pathophysiology of pruritus in atopic dermatitis: an overview.
AB  - Pruritus is an essential feature of atopic dermatitis (AD) and the diagnosis of
      active AD cannot be made without the history of itching. Because of the high
      impact on life quality, most of the patients measure the severity of eczema by
      the intensity of pruritus rather than appearance of skin lesions. However,
      although pruritus is a cardinal symptom of AD, its mechanism and association with
      the cutaneous nervous system is not completely understood. Recently, a
      considerable progress has been achieved in clarifying the complex pathophysiology
      of pruritus in AD. As a cutaneous sensory perception, itch requires excitation of
      neuropeptide-containing free nerve endings of unmyelinated nociceptor fibers. It
      is well known that histamine and acetylcholine provoke itch by direct binding to
      'itch receptors' and several mediators such as neuropeptides, proteases or
      cytokines indirectly via histamine release. Interestingly, some variations of
      these complex mechanisms could be demonstrated in patients with AD. This review
      highlights the recent knowledge of different mechanisms which may be involved in
      regulating pruritus in patients with AD potentially leading to new therapeutic
      applications for the treatment of itch in AD.

PMID- 11952825
TI  - Effect of protein kinase C on transmembrane calcium fluxes in HaCaT
      keratinocytes.
AB  - Capacitive calcium influx is associated with the release of calcium from internal
      stores and participates in intracellular calcium homeostasis. In keratinocytes,
      its activation is linked to the stimulation of the phospho-inositide (PI) pathway
      and seems to be altered in psoriasis. An overnight treatment of isolated HaCaT
      keratinocytes with phorbol 12-myristate 13-acetate (PMA) selectively
      downregulated the classical, calcium-dependent protein kinase C (PKC) isoenzyme
      PKC alpha in preconfluent cells. This was parallelled by an increased
      capacitative calcium influx with no effects on the PI pathway. These observations
      were strengthened in measurements using cyclopiazonic acid which revealed a 47%
      increase in PMA pretreated as compared with control cells in the calcium influx
      rate through store-operated calcium channels (SOC-s) following the emptying of
      the intracellular calcium stores. In confluent as compared with preconfluent
      cultures PKC epsilon was markedly increased, while other isoenzymes were not
      affected. In parallel, the kinetics of capacitative calcium influx were altered,
      showing clear inactivation. PMA pretreatment in these cells had little effect on
      PKC alpha but downregulated both PKC beta and PKC epsilon, and did not increase
      the influx through SOC-s. These observations support the differential regulation
      of SOC-s by PKC and suggest the involvement of several PKC isoenzymes in human
      keratinocytes.

PMID- 11952826
TI  - Intermediate or chronic cutaneous leishmaniasis: leukocyte immunophenotypes and
      cytokine characterisation of the lesion.
AB  - The American cutaneous forms of leishmaniasis include immune-responder
      individuals with localised cutaneous leishmaniasis (LCL) and non-responder
      individuals with diffuse cutaneous leishmaniasis (DCL). Patients with
      intermediate or chronic cutaneous leishmaniasis (ICL) have increased morbidity
      due to the length of their illness, atypical forms and areas of compromise. In
      the present study, we evaluated the expression of the leukocyte antigens (CD4,
      CD8, CLA: cutaneous lymphocyte antigen, CD69, CD83 and CD1a) and cytokines (IFN
      gamma, IL-4, IL-10 and TGF-beta 1) in the lesions of patients with ICL (n = 18)
      using an immunocytochemical procedure. ICL results were compared with the
      information for LCL (n = 19) and DCL (n = 4). The numbers of CD4+ and CD8+ T
      cells in ICL were similar to those of LCL lesions, but significantly different (P
      < or = 0.05) from DCL lesions. LCL lesions have about half the numbers of early
      activated CD69+ cells as ICL, but most are CLA+ skin homing memory T cells,
      whereas ICL lesions have the highest number of CD69+ T cells, but about one-third
      of these cells expressed CLA. This suggests that the granuloma of ICL patients
      contains many activated T cells that are unprimed to cutaneous-launched antigens,
      thus contributing to an aberrant immune response. In contrast, DCL granulomas
      presented the lowest numbers of activated CD69+ and CLA+ cells, associated with
      the characteristic tolerogenic state of these patients. The immunolocalisation of
      cytokines showed a mixed cytokine pattern in ICL lesions with many positive cells
      for IL-10, TGF-beta 1, IL-4 and IFN-gamma, with a preponderance of the first two,
      and different from the prevalent Th1 and Th2 responses associated with LCL and
      DCL lesions, respectively. CD1a+ Langerhans cells were decreased (P < or = 0.05)
      in both ICL (271 +/- 15 cells/mm2) and DCL (245 +/- 19 cells/mm2) as compared to
      LCL (527 +/- 54 cells/mm2) epidermis. The percentage of IL-10+ epidermal
      Langerhans cells in ICL (33.69), from the total CD1a+ population, was higher than
      in LCL (17.45). In addition, fewer CD83+ primed Langerhans cells were present in
      ICL epidermis. The diminished participation of epidermal Langerhans cells,
      causing a defective signalling by the epidermis, in ICL lesions may account for
      the tissue-damaging state observed in these patients.

PMID- 11952827
TI  - Expression of melanocortin-1 receptor in normal, malformed and neoplastic skin
      glands and hair follicles.
AB  - Melanocortin receptors (MC-Rs) are G-protein coupled receptors that mediate
      pleiotropic actions of melanocyte-stimulating hormones and adrenocorticotropin.
      There is increasing evidence that one of the five so far identified melanocortin
      receptors, i.e. melanocortin-1 receptor (MC-1R), has a more ubiquitous
      distribution in the skin than originally expected. In the present study, the
      expression of MC-1R in normal skin glands and hair follicles, various
      malformations and neoplasms with adnexal differentiation is described. Using an
      anti-MC-1R antibody directed against the amino acids 2-18 of the human MC-1R,
      specimens of normal healthy skin (n = 10) as well as hamartomas, cysts,
      hyperplasias, and benign or malignant neoplasms with eccrine, apocrine, sebaceous
      gland, and hair follicle differentiation (n = 98) were immunostained. MC-1R
      expression was widely preserved in various adnexal malformations and neoplasms as
      compared with normal skin and did not show major differences with regard to
      maturation of the neoplasms. The majority of adnexal epithelia showed an
      intracytoplasmically granular staining and, to a lesser extent, an intercellular
      staining pattern. Immunoelectron microscopical investigations revealed expression
      of MC-1R both along the cell surface and intracytoplasmically within tubular
      endosomes, the latter suggesting internalisation of the receptor. In conclusion,
      preserved MC-1R expression in adnexal epithelia suggests a functional role of
      proopiomelanocortin (POMC) in various malformations and neoplasms of the skin.

PMID- 11952828
TI  - Comparison of gene expression profiles in human keratinocyte mono-layer cultures,
      reconstituted epidermis and normal human skin; transcriptional effects of
      retinoid treatments in reconstituted human epidermis.
AB  - In order to validate a model for predictive screening of dermatological drugs, we
      used a customized cDNA macro-array system containing 475 skin-related genes to
      analyze the gene expression patterns in human keratinocytes from different
      origins: (1) normal human epidermal keratinocyte mono-layer cultures, (2) the
      commercially available SkinEthic reconstituted human epidermis model, and (3)
      biopsies of normal human epidermis. Few markers of those that were detected
      significantly in keratinocyte mono-layers or in reconstituted epidermis were
      undetected or detected at very low level in the normal epidermis biopsies. A
      comparative expression of more than 100 markers could be evidenced in both normal
      epidermis and reconstituted epidermis samples; however, only 90% of these were
      detected in keratinocyte mono-layers: expression of several terminal
      differentiation markers, such as filaggrin, loricrin, and corneodesmosin were
      strongly detected in normal epidermis and reconstituted epidermis, but were not
      significantly expressed in keratinocyte mono-layers. Under the experimental
      conditions described herein, the reconstituted human epidermis model was found to
      significantly reproduce the gene expression profile of normal human epidermis.
      Using the same methodology, we then investigated the effects of all-trans
      retinoic acid, 9-cis retinoic acid, all-trans retinol and a commercialized
      tretinoin-containing cream (Retacnyl) on the gene expression profiles of
      reconstituted human epidermis. According to the nature and the length of the
      treatments, more than 40 genes were found significantly modified. Among the genes
      whose expression was decreased, we found cytokeratins 1, 10, 2E, and 6B, several
      cornified envelope precursors, integrins alpha 3, alpha 6, beta 1, beta 4, some
      components of desmosomes, of hemi-desmosomes and of the epidermal basement
      membrane. Transcriptional upregulation was observed for keratins 18 and 19,
      autocrine and paracrine growth factors such as HB-EGF, IGF 1, PDGF-A,
      calgranulins A and B, interleukin-1 alpha and the other IL-1-related markers,
      type II IL-1 receptor and type I IL-1-receptor antagonist. Our results confirm
      most of the known effects of retinoids on human epidermis, but also give new
      insights into their complex pharmacological activity on skin. The reconstituted
      human epidermis used proves to be a highly predictive model for efficacy
      evaluation of skin-targeted compounds, such as retinoids.

PMID- 11952829
TI  - Comprehensive analysis of gene expression profiles in keratinocytes from patients
      with generalized atrophic benign epidermolysis bullosa.
AB  - Generalized atrophic benign epidermolysis bullosa [GABEB (OMIM no. 226650)] is an
      inherited subepidermal blistering disease typically caused by null mutations in
      COL17A1, the gene encoding type XVII collagen. Studies of GABEB keratinocytes
      homozygous for 4003delTC showed that this 2 bp deletion results in markedly
      reduced COL17A1 transcripts due to nonsense mediated-mRNA decay. To explore
      consequences of this null mutation in COL17A1 on the expression of other genes,
      RNA samples from reference GABEB and normal keratinocytes were profiled in
      comparative screens of microarrays of known cDNAs (n = 6180) and expressed
      sequence tags (ESTs) (n = 15 144). All comparative hybridization experiments were
      performed > or = twice; data were quantitated by densitometry and analyzed using
      peak quantification statistical comparative analysis (P-SCAN) software to
      identify differentially expressed genes. Representative genes found to be
      differentially expressed were verified using real-time reverse transcription
      polymerase chain reaction (RT-PCR). These experiments determined that expression
      of nonsense-mediated mRNA decay trans-acting factor (NMD-F), the regulator of
      nonsense transcripts (i.e. the human homolog of the yeast Upf1 protein), was
      upregulated in GABEB keratinocytes. NMD-F was subsequently found to be
      upregulated in cultured keratinocytes from other GABEB patients homozygous for
      4003delTC. These findings indicate that the gene responsible for nonsense
      mediated mRNA decay is upregulated in keratinocytes known to eliminate mutant
      COL17A1 transcripts via this highly conserved mechanism.

PMID- 11952833
TI  - The gamma-tubulin complex protein Alp4 provides a link between the metaphase
      checkpoint and cytokinesis in fission yeast.
AB  - BACKGROUND: The progression of cytokinesis requires cyclin B destruction by the
      anaphase promoting complex (APC/C) and, in fission yeast, activation of the
      septation initiation network (SIN) is also essential. The gamma-tubulin complex
      (gamma-TuC) localizes to the centrosome throughout the cell cycle and is directly
      involved in the organization of the mitotic spindle. RESULTS: We have previously
      shown that the mutant defective in alp4+ (Spc97/GCP2) displays bipolar spindle
      defects due to a failure in the recruitment of the gamma-TuC on to the spindle
      pole body (SPB, the centrosome equivalent). Here we show that in these mutants
      the Mad2 checkpoint is activated, yet septation proceeds due to the untimely
      activation of the SIN. The Sid1 kinase, the downstream effector of the SIN, is
      recruited prematurely to both, instead of only one, of the SPBs, which triggers
      septation despite the presence of monopolar spindles. Remarkably, cyclin B
      levels, which would normally have declined, remain high at the SPB in septated
      mutant cells. CONCLUSIONS: We propose a novel role of the gamma-TuC in inhibiting
      activation of the SIN until cyclin B is destroyed. Given the ubiquitous existence
      of the gamma-TuC, this mechanism may be conserved throughout evolution and
      function to couple cytokinesis to mitotic exit.

PMID- 11952832
TI  - Gene products encoded in the ninR region of phage lambda participate in Red
      mediated recombination.
AB  - BACKGROUND: The ninR region of phage lambda contains two recombination genes, orf
      (ninB) and rap (ninG), that were previously shown to have roles when the RecF and
      RecBCD recombination pathways of E. coli, respectively, operate on phage lambda.
      RESULTS: When lambda DNA replication is blocked, recombination is focused at the
      termini of the virion chromosome. Deletion of the ninR region of lambda decreases
      the sharpness of the focusing without diminishing the overall rate of
      recombination. The phenotype is accounted for in large part by the deletion of
      rap and of orf. Mutation of the recJ gene of the host partially suppresses the
      Rap- phenotype. CONCLUSION: ninR functions Orf and Rap participate in Red
      recombination, the primary pathway operating when wild-type lambda grows
      lytically in rec+ cells. The ability of recJ mutation to suppress the Rap-
      phenotype indicates that RecJ exonuclease can participate in Red-mediated
      recombination, at least in the absence of Rap function. A model is presented for
      Red-mediated RecA-dependent recombination that includes these newly identified
      participants.

PMID- 11952834
TI  - Tropomyosin is required for the cell fusion process during conjugation in fission
      yeast.
AB  - BACKGROUND: Tropomyosin is an actin-binding protein, which is thought to
      stabilize actin filaments and influence many aspects of F-actin. In fission
      yeast, the cdc8 gene encodes tropomyosin, and the gene product Cdc8p is known to
      be essential for the formation of the F-actin contractile ring and hence for
      cytokinesis in the mitotic cell cycle. RESULTS: We isolated fission yeast mutants
      that were defective in cell fusion during conjugation. One of them turned out to
      carry a point mutation in cdc8. We found that the original temperature-sensitive
      cdc8 mutant frequently failed to undergo cell fusion when mated at a semi
      permissive temperature. Additional cdc8 mutants isolated by targeted mutagenesis
      also showed defects in both cell fusion and cytokinesis. A decrease in the amount
      of intracellular Cdc8p also affected both, but cell growth was more severely
      blocked than cell fusion in this case. Immunostaining revealed that Cdc8p was
      localized as a spot at the cell-to-cell attachment site during conjugation,
      without overlapping with F-actin patches. CONCLUSIONS: Tropomyosin Cdc8p is
      indispensable for cell fusion during conjugation in fission yeast. However, cell
      fusion appears to require fewer tropomyosin molecules than cytokinesis. We
      speculate that tropomyosin may organize a small F-actin-containing organelle at
      the cell-to-cell contact site in each mating cell, which plays a key role in cell
      fusion.

PMID- 11952835
TI  - Hyper-processive and slower DNA chain elongation catalysed by DNA polymerase III
      holoenzyme purified from the dnaE173 mutator mutant of Escherichia coli.
AB  - BACKGROUND: A strong mutator mutation, dnaE173, leads to a Glu612 --> Lys amino
      acid change in the alpha subunit of Escherichia coli DNA polymerase III (PolIII)
      holoenzyme and abolishes the proofreading function of the replicative enzyme
      without affecting the 3' --> 5' exonuclease activity of the epsilon subunit. The
      dnaE173 mutator is unique in its ability to induce sequence-substitution
      mutations, suggesting that an unknown function of the alpha subunit is hampered
      by the dnaE173 mutation. RESULTS: A PolIII holoenzyme reconstituted from dnaE173
      PolIII* (DNA polymerase III holoenzyme lacking the beta clamp subunit) and the
      beta subunit showed a strong resistance to replication-pausing on the template
      DNA and readily promoted strand-displacement DNA synthesis. Unlike wild-type
      PolIII*, dnaE173 PolIII* was able to catalyse highly processive DNA synthesis
      without the aid of the beta-clamp subunit. The rate of chain elongation by the
      dnaE173 holoenzyme was reduced to one-third of that determined for the wild-type
      enzyme. In contrast, an exonuclease-deficient PolIII holoenzyme was vastly prone
      to pausing, but had the same rate of chain elongation as the wild-type.
      CONCLUSIONS: The hyper-processivity and slower DNA chain elongation rate of the
      dnaE173 holoenzyme are distinct effects caused by the dnaE173 mutation and are
      likely to be involved in the sequence-substitution mutagenesis. A link between
      the proofreading and chain elongation processes was suggested.

PMID- 11952836
TI  - Inhibition of Nodal signalling by Lefty mediated through interaction with common
      receptors and efficient diffusion.
AB  - BACKGROUND: Two TGFbeta-related proteins, Nodal and Lefty, are implicated in
      early embryonic patterning of vertebrates. Genetic data suggest that Nodal is a
      signalling molecule, while Lefty is an antagonist of Nodal, but their precise
      function remains unknown. RESULTS: The signalling pathway of Nodal was
      investigated with the use of a Nodal-responsive assay system based on frog animal
      caps. Expression of dominant negative mutants of various receptors indicated that
      ALK4, and either ActRIIA or ActRIIB, function as type I and type II receptors for
      Nodal, respectively. A soluble form of Cripto lacking the COOH-terminal region
      interacted with Nodal but failed to mediate Nodal signalling, indicating that the
      native Cripto protein functions as a membrane-bound co-receptor for Nodal.
      Processed forms of Lefty proteins, both smaller and larger forms, inhibited Nodal
      signalling. Such Lefty-induced inhibition was rescued by excess ActRIIA or
      ActRIIB, suggesting that Lefty antagonizes Nodal signalling through competitive
      binding to the common receptor ActRIIA or ActRIIB. This idea was supported by the
      demonstration of a genetic interaction between lefty2 and ActRIIB in mouse.
      Behaviours of GFP-Nodal and GFP-Lefty2 proteins were also investigated in chick
      embryos. Both proteins could diffuse over a long distance, but the latter
      diffused faster than the former. CONCLUSIONS: Efficient inhibition of Nodal
      signals by Lefty may involve competitive binding of Lefty to the common receptors
      and faster diffusion of Lefty.

PMID- 11952837
TI  - Association of frabin with specific actin and membrane structures.
AB  - BACKGROUND: Frabin is an actin filament (F-actin)-binding protein with GDP/GTP
      exchange activity specific for Cdc42 small G protein. Expression of frabin forms
      filopodia-like microspikes through the direct activation of Cdc42, and
      lamellipodia through indirect activation of Rac small G protein. Frabin consists
      of the F-actin-binding domain (FAB), the Dbl homology domain (DH), the first
      pleckstrin homology domain (PH1), the FYVE-finger domain (FYVE), the second PH
      domain (PH2) from the N-terminus in this order. Although DH and PH1 show exchange
      activity, FAB, in addition to DH and PH1, is required for the formation of
      microspikes, whereas FYVE and PH2, in addition to DH and PH1, are required for
      the formation of lamellipodia. RESULTS: Various truncated mutants of frabin were
      co-expressed with a dominant active mutant (DA) of Cdc42, Rac1DA, or full-length
      frabin in L fibroblasts. FAB was recruited to the Cdc42DA-formed filopodia-like
      microspikes. FAB and a fragment containing DH, PH1, FYVE and PH2 were recruited
      to the Rac1DA-formed membrane ruffles. Furthermore, each of these fragments
      served as a dominant negative mutant of frabin when co-expressed with full-length
      frabin, and inhibited the full-length frabin-formed morphological changes.
      CONCLUSION: These results suggest that frabin recognizes a specific actin
      structure(s) through FAB and a specific membrane structure(s) through FAB and the
      region containing DH, PH1, FYVE and PH2. It is likely that frabin associates with
      the specific actin and membrane structures and activates Cdc42 and Rac in the
      vicinity of these structures, eventually leading to morphological changes.

PMID- 11952838
TI  - Nucleocytoplasmic transport of proteins and poly(A)+ RNA in reconstituted Tpr
      less nuclei in living mammalian cells.
AB  - BACKGROUND: It is known that Tpr is a component of an intranuclear long filament
      which extends from the nuclear pore complex (NPC) into the nucleoplasm. Since the
      over-expression of the full-length of or some fragments of Tpr in living cells
      leads to the accumulation of poly(A)+ RNA within the nuclei, it is generally
      thought that a relationship exists between Tpr and the nuclear export of mRNA in
      mammalian cells. In contrast, the nuclear export of poly(A)+ RNA was not
      inhibited in a double deletion mutant of yeast Tpr homologues (Mlp1p and Mlp2p).
      Therefore, the precise function of Tpr remains unknown. RESULTS: By
      microinjecting two types of polyclonal antibodies which are specific to Tpr into
      the cytoplasm of living mammalian interphase cells, we succeeded in
      reconstituting the Tpr-less nuclei. In the Tpr-less nuclei, the localization of
      the major components of the NPC, the nuclear import of SV40 T-NLS substrates and
      the nuclear export of HIV Rev NES-substrates were not affected. However poly(A)+
      RNA accumulated in the non-snRNP splicing factor SC35-positive clusters, which
      became larger in size and fewer in number, compared with normal nuclei.
      CONCLUSION: These results indicate that Tpr plays a critical role in the
      intranuclear dynamics of RNA pol II transcripts, including the processing,
      intranuclear transport and targeting, as well as their translocation through the
      NPC in mammalian cells.

PMID- 11952840
TI  - Factor VIII and transmissible spongiform encephalopathy: the case for safety.
AB  - Haemophilia A is the most common inherited bleeding disorder, caused by a
      deficiency in coagulation factor VIII (FVIII). Current treatment of haemophilia A
      is based on repeated infusions of plasma-derived FVIII concentrate or of
      recombinant FVIII, which may be exposed to plasma-derived material of human or
      animal origin used in its tissue culture production process. We review
      epidemiological and experimental studies relevant to blood infectivity in the
      transmissible spongiform encephalopathies (TSEs, or 'prion' diseases), and
      evaluate the hypothetical risk of TSE transmission through treatment with plasma
      derived or recombinant FVIII.

PMID- 11952839
TI  - Identification of a novel transcription factor, ELYS, expressed predominantly in
      mouse foetal haematopoietic tissues.
AB  - BACKGROUND: The precise mechanism governing the generation of haematopoietic stem
      cells still remains to be understood, partly because the molecules required for
      early haematopoiesis have not fully been identified. RESULTS: We have identified
      a novel gene expressed in embryonic haematopoietic tissues, designated ELYS (for
      embryonic large molecule derived from yolk sac), which has no significant
      homology with any other known molecules. Based on the cDNA sequence, mouse ELYS
      protein is composed of 2243 amino acid residues and contains an AT-hook DNA
      binding domain, eight nuclear localization signals (NLSs) at the C-terminal
      region, three nuclear export signals (NESs) and two WD repeats at the N-terminal
      region. ELYS has a potential to shuttle between the cytoplasm and nucleus. When
      in the nucleus, ELYS is present in the nuclear matrix. Fusions of the yeast GAL4
      DNA-binding domain and various ELYS mutants reveal the presence of
      transcriptional activation and inhibitory domains. The ELYS gene is predominantly
      expressed in embryonic haematopoietic tissues, i.e. foetal liver, spleen, and
      thymus, whereas the expression is down-regulated in the adult. In the aorta-gonad
      mesonephros (AGM) region of an 11.5 dpc mouse embryo, ELYS is expressed in the
      endothelium lining the dorsal aorta. In the adult bone marrow, ELYS is notably
      expressed in the Lin-/c-kit+/Sca-1+ population. CONCLUSIONS: We have reported the
      isolation and characterization of a novel molecule, ELYS. ELYS seems to be a
      nuclear transcription factor associated with both early and mature haematopoietic
      events.

PMID- 11952841
TI  - Experience of prophylaxis treatment in children with severe haemophilia.
AB  - The practice of prophylactic treatment of boys with severe haemophilia has been
      evaluated in our centre. Prophylaxis was started at the median age of 3.7 years
      (range 0.4-12.7 years) in 38/41 children (93%) under 17 years of age. Median
      follow-up was 4.1 years (range 0.4-12.7 years). The criteria of primary
      prophylaxis according to the definition by the European Paediatric Network of
      Haemophilia Management was fulfilled by 9/38 (24%). Although a majority [76%,
      29/38] of the children started prophylaxis after a median number of joint bleeds
      of 3.5, 70% of the children in this group had clinical joint scores of 0.
      Intravenous catheter insertion was required at a median age of 15.5 months (range
      5-36 months) in 21% of the children, resulting in a catheter infection rate of
      1.74 per 1000 catheter days. None developed an inhibitor on prophylaxis and three
      patients who had low-titre inhibitors (< 5 Bethesda units) prior to prophylaxis
      had undetectable inhibitors after prophylaxis. The home-treatment training
      programme required considerable time and cost. As a result, 87% of the children
      used peripheral venous access and hospital visits declined as prophylaxis became
      established. Parents' incentives for prophylaxis were that the children undertook
      many physical activities and sports previously not recommended, there was less
      parental anxiety and an overall improvement in the quality of life for the whole
      family.

PMID- 11952842
TI  - Safety of factor VIII inhibitor bypass activity (FEIBA): 10-year compilation of
      thrombotic adverse events.
AB  - Published and unpublished spontaneously reported thrombotic adverse events (AEs)
      in factor VIII inhibitor bypass activity (FEIBA(R)) recipients were compiled for
      the most recent 10-year period during which FEIBA(R) units equivalent to 3.95 x
      105 typical infusions were distributed worldwide. A total of 16 thrombotic AEs
      were documented over the 10-year period, corresponding to an incidence of 4.05
      per 105 infusions (95% CI, 2.32-6.58 per 105 infusions). Disseminated
      intravascular coagulation (n=7) and myocardial infarction (n=5) were the most
      frequent thrombotic AEs. One fatality occurred in an 87-year-old metastatic
      cancer patient. In 13/16 (81%) patients known risk factors were present, most
      commonly FEIBA(R) overdose in 8/16 (50%), obesity in 3/16 (19%) and serum lipid
      abnormalities in 2/16 (12%). These findings indicate that thrombotic AEs in
      FEIBA(R) recipients are very rare. Recognition of risk factors and avoidance of
      FEIBA(R) overdosage may avert thrombotic AEs.

PMID- 11952843
TI  - Use of recombinant factor IX in subjects with haemophilia B undergoing surgery.
AB  - Recombinant human FIX (rFIX) was evaluated in 28 subjects, including 26 with
      mild, moderate, or severe haemophilia B and two haemophilia B carriers undergoing
      36 surgical procedures. Preoperative rFIX dose was highly correlated with
      postinfusion FIX activity, r=0.61, P=0.0158. Peri- and post-operative estimated
      blood loss was similar to that expected in non-haemophilic individuals, and
      haemostasis was rated as excellent or good in 34 of 35 (97.1%) of the operative
      procedures. Transfusions were required in five of 36 (13.9%) procedures,
      including one liver transplantation, and three knee and one hip arthroplasties.
      Adverse events occurred in 15 of 28 (53.6%) subjects, but there were no
      perioperative haemorrhages, thromboembolic events, coagulation activation, viral
      transmission, or inhibitor formation. A transient low-responding FIX inhibitor
      developed in one subject preoperatively, but required no change in treatment and
      resolved 15 months later. Thus, rFIX was found to be safe and effective in
      achieving haemostasis in subjects with FIX deficiency undergoing surgery.

PMID- 11952844
TI  - Modified magnetic resonance imaging score compared with orthopaedic and
      radiological scores for the evaluation of haemophilic arthropathy.
AB  - Twenty-four joints (10 knees and 14 ankles), with at least one manifestation of
      bleeding (proven by sonographic assessment), of 15 patients with haemophilia were
      investigated prospectively. For magnetic resonance imaging (MRI) evaluation, the
      MRI scale of Nuss et al. was modified to a MRI score (max. 13 points/joint) to
      allow a comparison with the physical examination score (max. 12 points) and the
      radiological score (Pettersson score; max. 13 points). The number of joint bleeds
      correlated well with the degree of arthropathy P < 0.01). In all 16 joints with a
      maximum of two bleeds, no alterations were found by physical examination, or
      radiological and MRI assessment. Joints with three bleeds had physical
      examination scores between 0 and 2, Pettersson scores from 0 to 3 and MRI scores
      of 2. Joints with four or more bleeds had physical examination scores ranging
      between 3 and 7, radiological scores between 7 and 12 and MRI scores between 3
      and 8. The MRI score describes initial joint alterations more precisely and
      earlier than other assessments, allowing a discerning estimation of the degree of
      arthropathy, as well as a follow-up of haemophilic arthropathy and an improvement
      after change of treatment. In addition, the modified MRI score seems to
      differentiate better between early and advanced signs of arthropathy than the MRI
      scale of Nuss et al.

PMID- 11952845
TI  - Bone fractures in the haemophilic patient.
AB  - The goal of modern fracture treatment is to obtain an optimal outcome, with the
      patient's return to full activity as soon as possible. Nowadays, internal
      stabilization is indicated in most displaced fractures in adults, whereas
      external fixation remains the best choice for initial stabilization with severe
      soft-tissue injuries. If a fracture is correctly treated in a haemophilic
      patient, it will progress to consolidation in a similar time-frame to fractures
      occurring in the general population.

PMID- 11952846
TI  - Health-related quality-of-life treatments for severe haemophilia: utility
      measurements using the Standard Gamble technique.
AB  - Prophylaxis for haemophilia improves outcomes, but at a substantial cost. Cost
      utility analysis balances improvements seen in health-related quality of life
      (HRQoL) against costs, with the purpose of aiding healthcare decision-making.
      This analysis uses a measure of HRQoL known as utility. The objective of this
      study was to measure HRQoL (utility) values for states of health that result from
      on-demand therapy or prophylaxis. The HRQoL for different health states
      (including target joint bleeding, different intensities of prophylaxis, and
      indwelling intravenous catheters [ports]) was measured for healthy adults (n=30),
      parents of haemophilic children (n=30), and adults with haemophilia (n=28).
      Parents and patients rated health states similarly. Healthy adults gave the
      lowest ratings. The following rank, in order of HRQoL, was obtained: prophylaxis
      (low > medium > high) > on-demand therapy > prophylaxis with port> prophylaxis
      with infected port > on-demand therapy with development of a target joint. We
      conclude that: (1) haemophilia and its treatment reduce HRQoL; (2) prophylaxis is
      preferred to on-demand therapy; (3) intravenous ports substantially reduce HRQoL;
      (4) and an intravenous port to provide prophylaxis is preferable to on-demand
      therapy if a target joint develops.

PMID- 11952847
TI  - Haemophilia Utilization Group Study: assessment of functional health status in
      haemophilia.
AB  - The purpose of this study was to assess the relationship between health care and
      utilization of that health care, and to provide a base measurement of health
      status in patients with haemophilia. Provider interview and retrospective chart
      review of 336 patients with haemophilia treated during 1995 at one of five
      comprehensive haemophilia treatment centres was conducted to measure patient
      health status characteristics and utilization of health care. Two health status
      scales were included. The first, the Self-Care Measure, was a four-point single
      item scale measuring the patient's ability for basic self-care, which was scored
      by a chart review and an interview with the health-care provider. The second, the
      Haemophilia Utilization Group Study (HUGS) Functional Status Measure, is a four
      item, 10-point scale developed specifically for patients with haemophilia. Our
      sample represents 27% of actively treated patients in region IX. The mean score
      on the HUGS Functional Status Measure was 8.7 (SD=2.4). The HUGS scale exhibited
      a ceiling effect across all four scales: attitude (n=269, 80.1%), overall
      wellbeing (n=263, 78.3%), working (n=254, 75.6%) and orthopaedic status (n=195,
      58.0%). Both higher total health-care costs and factor VIII annual costs were
      significantly associated with lower scores on the HUGS Functional Status Measure.
      Health status is a critical component in the assessment of the utilization and
      outcomes of care. In the absence of the availability of a patient interview, the
      HUGS Functional Status Measure can be used as one characteristic that explains
      the variation in the utilization of health care by patients with haemophilia.

PMID- 11952848
TI  - A randomized study of alpha-interferon plus ribavirin for 6 months or 12 months
      for the treatment of chronic hepatitis C in patients with bleeding disorders.
AB  - Little is known about the optimal treatment in patients with chronic hepatitis C
      virus (HCV) who were infected by pooled plasma products. The aim of our study was
      to compare the efficacy of 6 and 12 months of combination therapy with interferon
      alpha-2b and ribavirin in patients with bleeding disorders and chronic HCV. In a
      randomized open study, 61 patients with haemophilia or von Willebrand disease
      received treatment with a combination of interferon alpha-2b and ribavirin at
      standard dosage for 6 or 12 months. Follow-up was done with analysis of HCV RNA
      after an additional 6 months. The prevalence of HCV genotype 1 was 67%. Overall,
      sustained viral response was achieved in 41%; 13 of 30 patients (43%) treated for
      6 months vs. 12 of 31 patients (39%) treated for 12 months. The rate of sustained
      response was 22% in those with HCV genotype 1 and 80% in other genotypes (100% in
      genotype 2), with no difference between the treatment durations. The number of
      early discontinuations due to side-effects was 3 and 9, respectively. The study
      was stopped prematurely due to introduction of a more effective regimen, and the
      numbers are not sufficient to state equality. We conclude that the efficacy and
      safety of combination therapy against chronic hepatitis C in patients infected by
      pooled plasma products is similar to that observed in other populations. Six
      months of therapy seems sufficient in the case of HCV genotype 2. For other
      genotypes, the decision regarding duration of therapy has to be based on the
      tolerance of the individual patient together with experiences from other studies.

PMID- 11952849
TI  - Massive retroperitoneal pseudotumour in a patient with type 3 von Willebrand
      disease.
AB  - Formation of destructive haemorrhagic pseudocysts or pseudotumours thought to
      arise from unresolved, encapsulated haematomas is a well-recognized, rare
      complication of severe haemophilia A or B, and has been reported in a single
      patient with von Willebrand disease (vWD). We report a 41-year-old patient with
      type 3 vWD who underwent incomplete resection of a large retroperitoneal
      pseudocyst in 1995 and presented with a recurrent, extensive right abdominal and
      flank mass and signs and symptoms of large bowel obstruction. He required
      emergency partial colectomy for bowel ischaemia and removal of his right kidney,
      which was hydronephrotic due to prolonged ureteral obstruction by the pseudocyst.
      Following repeat partial resection of the pseudotumour, he developed persistent
      bleeding into the operative site despite aggressive administration of von
      Willebrand factor (vWF)-rich factor VIII concentrates, resulting in
      retroperitoneal haematomas and abscesses, which resolved after 13 months of
      percutaneous drainage, extended supplementation of vWF and antibiotic therapy.

PMID- 11952850
TI  - Efficacy of desmopressin as surgical prophylaxis in patients with acquired von
      Willebrand disease undergoing thyroid surgery.
AB  - Coagulation abnormalities may occur in patients with thyroid diseases. We report
      on 14 patients undergoing thyroid surgery for a thyroid disease with an
      alteration of coagulation parameters resembling von Willebrand disease.
      Subcutaneous desmopressin was first tested and then used successfully in these
      patients as surgical prophylaxis, with no side-effects or bleeding complications
      during or after surgery. This study highlights the need for coagulation studies
      in patients with thyroid diseases undergoing thyroid surgery. Subcutaneous
      desmopressin may be used in these patients in order to prevent a surgically
      related bleeding risk.

PMID- 11952851
TI  - Successful use of recombinant factor VIIa in a patient with inhibitor secondary
      to severe factor XI deficiency.
AB  - Factor XI (FXI) inhibitors are a rare complication of inherited FXI deficiency.
      We report the successful use of recombinant factor VIIa (FVIIa) in a patient with
      a high-responding inhibitor undergoing cataract extraction. At the time of
      surgery there were limited available data on the optimal management of patients
      with FXI deficiency. A 62-year-old Ashkenazi Jewish woman had a lifelong history
      of excessive bleeding secondary to severe FXI deficiency (2 U dL-1), and received
      FXI concentrate (FXI:C) when she underwent a colposuspension procedure. She was
      subsequently diagnosed with a FXI inhibitor of 16 Bethesda units (BU) when she
      developed a poor response to FXI:C at the time of total hip replacement. Two
      months later she was admitted for cataract extraction. The FXI level was < 1 U dL
      1 with an inhibitor titre of 48 BU. She received 90 microg kg-1 of FVIIa
      immediately preoperatively followed by continuous infusion at a rate of 20 microg
      kg-1 h-1 for 24 h. The cataract extraction was successful and there was no excess
      bleeding during surgery or in the postoperative period. Mutation analysis of the
      FXI gene showed that the patient was homozygous for the type II genotype [exon 5,
      Glu117-->Ter]. The reason for the low prevalence of inhibitor formation in
      patients with FXI deficiency is unclear but may reflect a number of factors
      including reporting bias, the rarity of absent circulating FXI:C activity, and
      the infrequent use of FXI replacement therapy.

PMID- 11952853
TI  - Observations from Global Survey 2001: an emerging database for progress.

PMID- 11952852
TI  - Long-term follow-up after intertrochanteric varus osteotomy for haemophilic
      arthropathy of the hip.
AB  - In view of an increasing tendency in prosthetic management of haemophilic
      arthropathy, we intended to evaluate the efficacy of corrective osteotomy of the
      hip, specifically taking long-term clinical and radiographic results into
      consideration. Eleven hips affected by haemarthropathy in nine patients suffering
      from severe haemophilia A were treated with an intertrochanteric varus osteotomy.
      The average follow-up period was 15 small middle dot4 years. The preoperative
      clinical score of the Advisory Committee of the World Federation of Haemophilia
      was 5 small middle dot3 points (range 4-7) and the Pettersson score was 6 small
      middle dot4 points (range 2-10). The average WFH score at follow-up had increased
      to 3 small middle dot6 points. Seven hips showed clinical improvement, two hips
      showed a postoperative deterioration while a further two hips remained unchanged.
      The Petterson score increased to an average of 7 small middle dot7 points. Here
      the radiographs of six patients indicated postoperative deterioration, three
      remained unaltered and two showed improvement. Our study cannot conclusively
      answer whether intertrochanteric varus osteotomy for haemophilic arthropathy of
      the hip is always a feasible alternative to joint arthroplasty. The decision for
      or against this procedure must be individually assessed and the patient must be
      thoroughly informed about the advantages and disadvantages of both procedures.

PMID- 11952854
TI  - Genomic interaction in haemophilia: uncharted territory.

PMID- 11952855
TI  - Marginal zone cell lymphoma--an update on recent advances.
AB  - The marginal zone represents one of the distinct compartments of the B-cell area
      in lymphoid tissues. It is especially well developed in the spleen and in Peyer's
      patches of the gut, but not in lymph nodes, with the exception of the ones in the
      mesenterium. However, the pronounced proliferation of so-called 'monocytoid B
      cells' that may be seen in some inflammatory conditions of the lymph node may be
      regarded as a nodal reactive marginal zone cell expansion. The cellular
      compositions of the marginal zone and the monocytoid B-cell proliferation are
      similar and both show a heterogeneous population of B-cells, of which the
      functions are being slowly unravelled. Neoplasms originating in the marginal zone
      have been recognized in the past and are listed in the REAL classification as
      marginal zone B-cell lymphomas including extranodal MALT-type lymphomas, splenic
      marginal zone lymphomas and nodal (monocytoid) marginal zone lymphomas. Marginal
      zone cell lymphomas display a broad morphological spectrum, which is reflected by
      the heterogeneity of the cellular composition and the variation in the growth
      pattern of the lymphoma, but is independent of the anatomical site. All three
      marginal zone cell lymphomas share immunophenotypic, genetic and chromosomal
      similarities which will be discussed. The morphologic features are dealt with
      only briefly as they have been extensively discussed elsewhere.

PMID- 11952856
TI  - Tumour 'budding' as an index to estimate the potential of aggressiveness in
      rectal cancer.
AB  - AIMS: Although the characteristic of invasive pattern which contributes to Jass's
      classification is a sensitive prognostic marker in rectal cancer, reproducibility
      of its assessment has been shown to be problematic. As another histological
      parameter of invasive margin, we examined the prognostic significance of tumour
      'budding' and attempted to establish its appropriate criteria. METHODS AND
      RESULTS: A total of 638 rectal cancer specimens was examined. We defined tumour
      'budding' as an isolated single cancer cell or a cluster composed of fewer than
      five cancer cells. We divided these into two groups by their intensity, i.e. the
      number of 'budding' foci within a microscopic field of x 250. Rectal cancer with
      high-grade 'budding' (>or= 10 foci in a field) was observed in 30.1% of patients,
      and was associated with lower 5-year survival rates (40.7%) than patients with
      low-grade 'budding' (84.0%) (P < 0.0001). Based on multivariate analysis, tumour
      'budding' was selected as the significant independent variable, together with the
      number of nodes involved, extramural spread, lymphocytic infiltration, apical
      nodal involvement and tumour differentiation. Kappa coefficient of two-graded
      tumour 'budding' in the intraobserver study was 0.84. CONCLUSIONS: Because of its
      value as a prognostic indicator and its reproducibility, tumour 'budding' would
      be a good index to estimate the aggressiveness of rectal cancer.

PMID- 11952857
TI  - Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary
      thyroid carcinoma-related neoplastic lesions with Hurthle cell and/or apocrine
      like changes.
AB  - BACKGROUND: We have recently observed that Hurthle cell tumours and papillary
      thyroid carcinoma with tumour cells showing decapitation of luminal portion of
      the cytoplasm (apocrine-like changes) display negative or decreased
      immunoreactivity for HBME. The purpose of this study is to correlate papillary
      thyroid carcinoma with positive and negative immunoreactivity for HBME with the
      histopathological features. METHODS AND RESULTS: Two hundred and five thyroid
      neoplasms including carcinoma and adenomas were grouped into Hurthle cell
      tumours, tumours with or without some features of Hurthle cells, tumours with
      apocrine-like changes and adenomas with or without limited nuclear features of
      papillary thyroid carcinoma but not diagnostic for papillary thyroid carcinoma.
      All neoplasms were submitted for immunostaining with cytokeratin 19 (CK19) and
      HBME. Papillary thyroid carcinoma, follicular carcinoma and follicular adenoma
      that have areas of limited nuclear features but not diagnostic for papillary
      thyroid carcinoma showed stronger immunostaining for HBME than their respective
      counterparts with Hurthle cell changes. All Hurthle cell tumours showed negative
      to focal reactivity. This decrease of reactivity for HBME was proportional to the
      levels of Hurthle cell changes. In addition, focal to extensive apocrine-like
      changes were seen in most Hurthle cell neoplasms and rarely seen in non-Hurthle
      cell neoplasms. Apocrine-like changes abolished or decreased HBME
      immunoreactivity of papillary thyroid carcinoma and tumours with limited nuclear
      features. Immunostaining for cytokeratin AE3 was not affected by Hurthle cell or
      apocrine-like changes. CONCLUSIONS: All papillary thyroid carcinomas without
      Hurthle cell or apocrine-like differentiation are reactive for HBME. Hurthle cell
      tumours and tumours with Hurthle cell or apocrine-like changes show negative or
      focal reactivity for HBME. Except for this limitation, HBME is a sensitive marker
      for papillary thyroid carcinoma and tumours with limited nuclear features.

PMID- 11952858
TI  - Expression of metallothionein in lung carcinoma: correlation with histological
      type and grade.
AB  - AIMS: Over-expression of cellular metallothionein occurs frequently in human
      tumours but the underlying mechanism remains unknown. The aim of this study was
      to assess metallothionein expression in cases of lung carcinoma and to correlate
      it with histopathological parameters. METHODS AND RESULTS: Tumour tissue samples
      from 89 patients with lung carcinoma were immunostained by the streptavidin
      biotin-peroxidase technique, using a monoclonal antibody against both
      metallothionein-1 and -2 isoforms. Positive matallothionein immunostaining was
      prominent in 44 out of 89 (49%) and negative in 45 out of 89 (51%) cases of lung
      carcinoma examined. Metallothionein positivity was prominent in 32 out of 43
      (74%) cases of squamous cell lung carcinoma, and in 12 out of 35 (34%) cases of
      adenocarcinoma, while it was negative in all 11 cases of small-cell lung
      carcinoma examined, presenting a statistically significant difference between the
      different histological types. The intensity of metallothionein staining revealed
      a statistically significant difference between the squamous cell and
      adenocarcinoma cases examined. The pattern and extent of metallothionein staining
      in tumour cells and the expression of metallothionein in stromal cells were not
      correlated with histopathological parameters (type and grade) in metallothionein
      positive cases of lung carcinoma examined. No association was found between
      metallothionein expression and lymph node status in the examined cases of lung
      carcinoma. CONCLUSIONS: Our findings indicate that expression of metallothionein
      was evident in squamous cell lung carcinoma and adenocarcinoma, but absent in
      small-cell lung carcinoma, supporting evidence for participation of this protein
      in the biological mechanisms underlying the carcinogenic evolution in the lung.

PMID- 11952859
TI  - Immunohistochemical markers in the differentiation of thymic and pulmonary
      neoplasms.
AB  - AIMS: The histopathological features of some thymic neoplasms overlap with those
      of pulmonary squamous and large-cell undifferentiated carcinomas, and
      identification of the primary site may be difficult on routine staining. We have
      assessed a panel of antibodies that may help to distinguish between neoplasms
      from these two sites. METHODS AND RESULTS: Antibodies identifying cytokeratin 7
      (CK7), CD5, CD10, CD1a and thyroid transcription factor-1 (TTF-1) were applied to
      a series of 20 thymic neoplasms (thymic carcinomas, atypical thymomas and
      thymomas), 10 primary squamous cell carcinomas of the lung and 10 large-cell
      undifferentiated carcinomas of the lung. Staining for TTF-1 was positive in 3/10
      large-cell undifferentiated carcinomas, but negative in all other tumours. CD5
      showed strong membranous staining in 3/6 thymic carcinomas and 1/14 thymomas, but
      only focal staining in 1/20 pulmonary carcinomas. CD1a was consistently positive
      in thymic lymphocytes in both typical and atypical thymomas, but only focally in
      1/6 thymic carcinomas. CD1a stained dendritic cells in 7/20 pulmonary carcinomas,
      but did not stain lymphocytes. Staining for CK7 and CD10 did not aid in
      differentiating between a pulmonary or thymic origin of the tumour. CONCLUSION:
      Staining for TTF-1, CD5 and CD1a have potential use in distinguishing between
      pulmonary and thymic neoplasms.

PMID- 11952860
TI  - Pigmented spindle cell carcinoid tumour of the thymus with ectopic
      adrenocorticotropic hormone secretion: report of a rare variant and differential
      diagnosis of mediastinal spindle cell neoplasms.
AB  - AIMS: A variety of histological variants of thymic carcinoid tumour have been
      described. A rare case of pigmented spindle cell carcinoid tumour of the thymus
      is documented and compared with the reported cases of thymic pigmented carcinoid
      tumour in the literature, with a discussion of the differential diagnosis of
      spindle cell tumours of the mediastinum. METHODS AND RESULTS: A thymic tumour
      with ectopic adrenocorticotropic hormone (ACTH) secretion was resected from a 24
      year-old man suffering from Cushing's syndrome. Histological,
      immunohistochemical, and ultrastructural studies revealed an ACTH-producing
      spindle cell carcinoid tumour harbouring pigmented melanocytes. Among four thymic
      pigmented carcinoid tumours reported before, only one was similar to the present
      case by being also an ACTH-secreting pigmented spindle cell thymic carcinoid
      tumour. The clinicopathological features of this tumour distinguish it from a
      spindle cell thymoma, spindle cell thymic carcinoma, and other mediastinal
      spindle cell tumours. CONCLUSIONS: This case illustrates an extremely rare
      variant of thymic carcinoid tumour exhibiting a spindle cell morphology and
      harbouring pigmented melanocytes. Awareness of this histological variant is
      important in the differential diagnosis of spindle cell tumours of the
      mediastinum.

PMID- 11952861
TI  - Immunohistochemical detection of CD30 remains negative in nodular lymphocyte
      predominant Hodgkin's disease using enhanced antigen retrieval.
AB  - AIMS: The aims of this study were to confirm that CD30 is reproducibly negative
      in cases of nodular lymphocyte-predominant Hodgkin's disease (nLPHD), and its
      relationship to further antibody targets for the distinction of L&H cells from
      classical Hodgkin's and Reed-Sternberg cells. METHODS AND RESULTS: We examined 16
      cases of nLPHD from two centres in the UK to characterize immunohistochemically
      L&H cells for CD30, EMA, J-chain and Oct2, using different methods of antigen
      retrieval, antigen amplification and antigen detection systems. Two cases could
      not be stained with J-chain and Oct2. All cases were negative for CD30 following
      manual and automated staining. Only one case became positive for EMA after manual
      staining using tyramide amplification. J-chain and Oct2 were negative in all
      cases following manual staining. J-chain showed a positive result of variable
      degree in all but one case using automated Dako ChemMate amplification system
      staining. Oct2 demonstrated a positive, albeit variable, staining pattern in all
      cases following automated staining. CONCLUSIONS: CD30 remains negative in L&H
      cells of nLPHD using enhanced antigen retrieval and can therefore reliably be
      used to distinguish nLPHD from classical Hodgkin's disease. The value of EMA in
      the diagnosis of nLPHD remains uncertain, as it does not reproducibly mark L&H
      cells, even after the use of enhanced antigen retrieval. J-chain and Oct2 appear
      to be useful markers in the diagnosis of nLPHD using enhanced immunostaining and
      should therefore be included in lymphoma panels. Automated enhanced staining,
      using standardized protocols, precoated slides and the full system of prepared
      reagents, further diminishes the occurrence of errors associated with manual
      staining, and thereby improves confidence and reliability in diagnosing nLPHD.

PMID- 11952863
TI  - Mucinous metaplasia of the penis.
AB  - AIMS: To determine the incidence of mucinous metaplasia occurring in the foreskin
      or glans penis and any associated clinical or histopathological features. METHODS
      AND RESULTS: Following the recognition of two index cases, 100 other foreskin
      specimens were retrieved from the histopathology archives at Southampton General
      Hospital. The haematoxylin and eosin-stained slides were examined by a single
      observer to detect the presence of mucin-producing cells in the surface
      epithelium. The absence of mucinous metaplasia in negative cases was confirmed
      with mucin histochemistry. In total, four cases of mucinous metaplasia were
      identified, three involving the foreskin and one involving the glans penis. The
      age range was 51-80 years. Three cases were associated with Zoon's balanitis and
      the fourth showed mild non-specific balanitis. All four cases showed positive
      staining with both diastase periodic acid-Schiff and alcian blue. No mucin
      producing cells were identified in non-inflamed or minimally inflamed specimens.
      CONCLUSIONS: Mucinous metaplasia of the penis is an uncommon but under-recognized
      condition. It is seen in the elderly and appears to be a metaplastic change
      associated with severe chronic inflammation, and possibly more specifically with
      Zoon's balanitis. Our study identified a case affecting the glans penis, a site
      not previously recorded.

PMID- 11952862
TI  - Primary endometrioid adenocarcinoma of the large intestine arising in colorectal
      endometriosis.
AB  - AIMS: Three cases of endometrioid adenocarcinoma arising in colorectal
      endometriosis are described with discussion of their macroscopic and microscopic
      pathology and diagnosis, using immunohistochemistry. METHODS AND RESULTS: Three
      middle-aged women presented with symptoms and signs of colorectal mass effect.
      Two had a preceding history of gynaecological endometriosis and all three had
      either been on hormone replacement therapy or had functioning ovaries prior to
      presentation with colorectal disease. Each underwent resection of tumours of the
      distal large intestine. The definitive diagnosis was dependent on histological
      examination and immunohistochemistry, which was used to demonstrate an origin in
      endometriotic tissue. CONCLUSIONS: Endometrioid adenocarcinoma is a rare
      complication of colorectal endometriosis, this report contributing to a total of
      25 cases in the literature. Definitive diagnosis, aided by immunohistochemical
      studies, is important to enable the identification of the optimal management for
      this uncommon condition.

PMID- 11952864
TI  - Photoreceptor cell differentiation in retinoblastoma demonstrated by a new
      immunohistochemical marker mucin-like glycoprotein associated with photoreceptor
      cells (MLGAPC).
AB  - AIMS: For further understanding of specific differentiation in retinoblastoma, we
      studied the expression of newly detected mucin-like glycoprotein associated with
      photoreceptor cells (MLGAPC), which is specific for photoreceptor cells of retina
      and analogous to interphotoreceptor matrix proteoglycan-1 (IMPG1). METHODS AND
      RESULTS: Surgically enucleated retinoblastomas (n=21; undifferentiated type,
      n=15, differentiated type, n=6) were immunohistochemically studied with a
      polyclonal antibody against MLGAPC, and 17/21 cases (81%) showed positive
      staining of tumour cells. We classified various staining patterns and structures
      into four groups: type 1 showing a granular intracellular scattered staining
      pattern with round small cells; type 2 showing a reticular staining pattern
      between spindle-shaped tumour cells; type 3 showing radiating staining from the
      centre of Homer-Wright rosettes; type 4 showing ring-shaped, radiating and
      granular staining associated with Flexner-Wintersteiner rosettes. Eleven of 15
      undifferentiated retinoblastomas (73%) showed type 1 or 2, and all the six
      differentiated cases showed type 3 or 4. Image analysis of immunostaining
      revealed an increase in MLGAPC-positive area from 0.48% in undifferentiated cases
      to 1.60% in differentiated cases, and a negative correlation was shown between
      mitotic frequency and MLGAPC-positive area. CONCLUSIONS: This study proved MLGAPC
      as a valuable marker of retinoblastoma, and that photoreceptor differentiation
      takes place even in 'undifferentiated' retinoblastoma.

PMID- 11952865
TI  - A study of eleven cutaneous malignant melanomas in adults with small-cell
      morphology: emphasis on diagnostic difficulties and unusual features.
AB  - AIMS: To describe the clinicopathological and immunohistochemical features of
      cutaneous malignant melanomas with a pure or mixed small-cell pattern in 11 adult
      patients, and to discuss the diagnostic difficulties encountered. METHODS AND
      RESULTS: Haematoxylin and eosin-stained sections of each case of cutaneous small
      cell malignant melanoma, together with locally recurrent skin lesions and, where
      available, metastatic deposits, were re-examined. Available immunohistochemical
      sections were evaluated. Clinical follow-up data were obtained in each case. One
      patient presented with metastatic disease, the others presented with cutaneous
      lesions. Suggested initial diagnoses included malignant melanoma, non-Hodgkin's
      lymphoma, Merkel cell carcinoma and sarcoma. All the tumours were in the vertical
      growth phase. Nine had a junctional component, often inconspicuous. The lesions
      showed either a pure small-cell pattern or a mixed pattern with more conventional
      areas. In one case, there was colonization of a basal cell carcinoma by invasive
      malignant melanoma. Variable retention of small-cell morphology in local
      recurrences and metastases was observed, although in some cases more typically
      pleomorphic cells were present. In the cases tested, there was strong
      immunostaining for S100 protein and NKI-C3, and variable immunostaining for HMB45
      and Melan-A. Non-melanocytic markers were negative. CONCLUSIONS: The possibility
      of a small-cell malignant melanoma should be considered in the assessment of
      cutaneous and non-cutaneous small-cell neoplasms. The correct diagnosis requires
      careful evaluation for junctional activity, melanin production and the use of a
      panel of melanocytic markers.

PMID- 11952867
TI  - Necrotizing sialometaplasia: a potential diagnostic pitfall.

PMID- 11952866
TI  - Small cell melanoma.

PMID- 11952868
TI  - Primary squamous cell carcinoma of the lung with pilomatricoma-like features.

PMID- 11952869
TI  - Multiple splenic nodules revealing Gaucher's disease.

PMID- 11952870
TI  - Hyaline bodies in ameloblastic fibro-odontoma.

PMID- 11952871
TI  - A morpholinocatechol compound (UK42620) with clonidine- and tyramine-like
      actions.
AB  - 1. The actions of a morpholinocatechol (UK42620) were studied in rat isolated
      atria preparations consisting of spontaneously beating left and right atrial
      pairs. 2. UK42620 produced positive inotropic and chronotropic responses and, in
      atria that were incubated with [(3)H]-noradrenaline, it also produced a massive
      increase in the release of radioactivity. 3. These actions of UK42620 were
      similar to those of tyramine and were blocked by the beta-adrenoceptor antagonist
      propranolol (0.3 microM) and by the neuronal uptake blocker desipramine (1
      microM). 4. In the presence of desipramine, UK42620 but not tyramine produced a
      decrease in the stimulation-induced efflux of radioactivity that was antagonized
      by idazoxan. 5. Thus, UK42620 had prejunctional alpha(2)-adrenoceptor activity
      like that of clonidine- and tyramine-like activity releasing large amounts of
      noradrenaline.

PMID- 11952872
TI  - Effect of in vivo and in vitro ethanol on adrenergic and purinergic responses of
      the bisected rat vas deferens to low and high frequency pulses.
AB  - 1. This study investigates the effect of acute in vivo and in vitro ethanol
      administration on the contractions evoked electrically and by exogenous
      noradrenaline and alpha,beta-methylene-ATP in the rat bisected vas deferens. 2.
      In vivo ethanol treatment (3 g kg(-1), i.p.) significantly potentiated the early
      purinergic (phase I) and the delayed adrenergic (phase II) phases evoked by
      single-pulse stimulation of the epididymal portion of the rat vas deferens,
      leaving unaffected both phases in the prostatic portion. In vitro 50 mM ethanol
      significantly depressed phase I leaving unaffected phase II in both portions from
      untreated rats. In vitro ethanol significantly depressed phase I in the
      epididymal portion from in vivo ethanol treated animals and potentiated phase II
      in both portions. 3. In vivo ethanol treatment (3.0 g kg(-1), i.p.) selectively
      impaired the response to noradrenaline only in the prostatic portion of rat vas
      deferens while it was devoid of any action on alpha,beta-methylene-ATP
      contractions. Ethanol 50 mM in vitro was devoid of any action on the response to
      exogenous noradrenaline and alpha,beta-methylene-ATP in both tissues. 4. In vivo
      ethanol treatment slightly but significantly increased the phasic response in the
      epididymal portion to trains of stimuli (2-30 Hz). In vitro 50 mM ethanol was
      ineffective against the phasic and tonic contractions elicited by the tetanus in
      both portions. 5. It is concluded that ethanol treatment affects purinergic and
      adrenergic pathways of transmission possibly leading to a disruption of
      physiological contractions necessary to seminal emission.

PMID- 11952873
TI  - P2X(7) receptors in rat parotid acinar cells: formation of large pores.
AB  - 1. Permeabilization of cells mediated by P2X(7) receptors occurs to varied
      degrees in native and heterologous expression systems. Previous studies on P2X(7)
      receptors in parotid acinar cells suggested that ATP does not permeabilize these
      cells. 2. Modification of the assay conditions showed that ATP permeabilizes
      freshly dissociated rat parotid acinar cells to the fluorescent dye YOPRO-1. 3.
      The pharmacological and physiological properties of this effect indicate that
      permeabilization is mediated by the P2X(7) receptor. Adenosine 5'-triphosphate
      (ATP) and 3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate (BzBzATP) were
      effective agonists with EC(50) values of 49.3 and 0.6 microM, respectively. 4.
      Permeabilization was best observed in low divalent cation concentrations and at
      physiological temperatures. Previous studies failed to detect permeabilization
      because of the sensitivity of this effect to temperature and divalent cations. 5.
      An important consideration in understanding the effect of divalent cations is
      that the fluorescence of YOPRO-1/nucleic acid complexes is directly quenched by
      addition of divalent cations. This must be considered if quantitative study of
      the interaction of divalent cations with P2X(7) receptors is carried out using
      fluorescent DNA-binding dyes. 6. In summary, our data show that P2X(7) receptors
      in parotid acinar cells can form large pores in the plasma membrane. This
      property likely contributes to signalling and may be cytotoxic and have
      particular significance in damaged or inflamed salivary glands.

PMID- 11952874
TI  - The effects of adenosine on isolated right atrial preparations from
      streptozotocin-diabetic rats.
AB  - 1. The aim of the present study was to investigate the inhibitory effects of
      adenosine on the contractile force and chronotropic action of isolated right
      atrial preparations from streptozotocin (STZ)-diabetic rats. 2. The rats were
      anaesthetized with diethyl ether and STZ (65 mg kg(-1)) was injected
      intravenously via the tail vein. 3. Adenosine produced concentration-dependent
      decreases in the force of contraction and a negative chronotropic action of atria
      both in control and diabetic groups. The inhibition responses to adenosine were
      significantly higher in diabetic rat atria than control. 4. Dypiridamole
      incubation caused a significant potentiation of the inhibitory effect of
      adenosine on contractile force and chronotropic action of atria in the control
      group, but not in the diabetic group. In the presence of dipyridamole, the
      inhibitory effects of adenosine on measured parameters in diabetic rats were not
      significantly different from those in control rats. 5. These results suggested
      that atria from 6 weeks STZ-diabetic rats exhibited a supersensitivity to the
      negative inotropic and chronotropic effects of adenosine compared with atria from
      control rats because of an impairment in adenosine uptake mechanism. Altered
      sensitivity to effects of adenosine might reflect relatively early changes in the
      course of diabetes.

PMID- 11952875
TI  - The influences of extremely low frequency magnetic fields on clonidine-induced
      sleep in 2-day-old chicks.
AB  - 1. It has been shown that magnetic fields (MFs) affect a variety of biological
      effects in animal brains. There have been few experiments on the effects of MFs
      on sleep. Therefore, we investigated whether extremely low frequency (ELF) MFs
      affect the sleep induced by clonidine, a central alpha(2)-adrenoceptor agonist.
      Clonidine produced dose-related increase of the sleeping time and dose-related
      decrease of the onset time in 2-day-old chicks. 2. Exposure of chicks to MFs (5,
      10, 20 G; for 3, 6, 9, 12 h) significantly increased the clonidine-induced sleep
      time as a direct function of intensity and duration of MF application. Clonidine
      reduced noradrenaline or tyrosine in the brain, an effect which was not further
      changed in animals exposed to MF. 3. To determine whether the gamma amino butyric
      acid A (GABA(A))/benzodiazepine (BZD) receptor system is involved in the decrease
      in clonidine-induced sleep caused by activation of central alpha(2)-adrenergic
      systems, we examined exposure of chicks to the effects of the BZD receptor
      antagonist flumazenil (0.5 mg kg(-1), i.p.) and GABA(A) antagonist bicuculline
      (0.1 mg kg-1, i.p.) on clonidine-induced sleep. Bicuculline and flumazenil
      inhibited the increase of clonidine-induced sleep time by MFs. Clonidine or MFs
      did not change GABA levels in the brain. 4. These results suggest that MFs can
      increase clonidine-induced sleep via a change of GABA(A) and BZD receptor system
      irrespective of the concentration of GABA or noradrenaline in the brain of 2-day
      old chicks.

PMID- 11952876
TI  - Contractile effects of tacrolimus in human and rat isolated renal arteries.
AB  - 1. We tested the vasoactive properties of the immunosuppressive drug FK 506
      (tacrolimus) in preconstricted rat and human isolated renal arteries in vitro. 2.
      In rat renal arteries, tacrolimus (3, 10 microM) showed a direct and dose
      dependent contractile effect by maximally 23 microm (10% of the noradrenaline
      effect), which was only observed in the presence of intact endothelium. Moreover,
      a lower concentration of tacrolimus (1 microM) potentiated pressor responses to
      the sympathetic neurotransmitter noradrenaline but not to ATP in this species.
      ATP- (0.01-10 microM) induced vasodilation was not affected by tacrolimus (1
      microM). 3. In contrast, in human interlobar arteries, tacrolimus failed to
      induce direct vasoconstriction and did not significantly potentiate constrictor
      responses to noradrenaline. Acetylcholine-(1 microM) induced vasodilation was
      much smaller in human than in rat renal arteries suggesting the lack of
      functional endothelium in the human preparation. 4. The findings suggest that
      tacrolimus releases an endothelium-derived constricting factor in rat renal
      arteries to increase vascular tone and to potentiate pressor responses to
      noradrenaline. In human interlobar arteries, this effect of tacrolimus is not
      observed probably because of the absence of functional endothelium or the
      necessary mediator mechanism.

PMID- 11952877
TI  - Racemic salbutamol administration to guinea-pigs selectively augments airway
      smooth muscle responsiveness to cholinoceptor agonists.
AB  - 1. An aim of this study was to investigate whether continuous in vivo
      administration of a low dose of salbutamol to guinea-pigs alters the
      responsiveness of airway smooth muscle in vitro. 2. Osmotic minipumps containing
      a solution of racemic salbutamol were implanted subcutaneously in guinea-pigs.
      The drug was infused at a dose of 0.2 mg kg(-1) day(-1) for 10 days and, at the
      end of that time, the trachea was isolated and concentration-response
      relationships to several contractile agonists were examined. 3. This treatment
      resulted in significant increases in the maximum tension developed by tracheal
      preparations in response to cholinoceptor agonists, carbachol and methacholine.
      4. Cumulative concentration-response curves for histamine, leukotriene D4, and
      KCl were similar in tracheal segments from saline-control and salbutamol-infused
      animals. 5. Time course experiments showed that augmented airway contractile
      responsiveness to cholinoceptor agonists was reversible within 3 days after
      cessation of the 10 day salbutamol infusion. 6. Our findings support the
      hypothesis that beta2-adrenoceptor agonist drugs, administered over time in vivo,
      induce a transient hyperresponsiveness of airway smooth muscle to cholinergic
      bronchoconstrictor stimuli.

PMID- 11952878
TI  - Does insulin preserve beta-cell function in type 2 diabetes?

PMID- 11952879
TI  - Prospects for chemoprevention of cancer.
AB  - The recent progress in molecular biology and pharmacology has increased the
      likelihood that cancer prevention will rely increasingly on interventions
      collectively termed 'chemoprevention'. Cancer chemoprevention is the use of
      agents to inhibit, delay or reverse carcinogenesis. A number of potential targets
      for chemoprevention have recently been identified. Many classes of agents
      including antioestrogens, anti-inflammatories, antioxidants and other diet
      derived agents have shown a great deal of promise. In this review, we will begin
      by describing the general classes of chemopreventive agents and the mechanisms by
      which these agents act. We will then describe the opportunities that presently
      exist for chemoprevention of specific cancers.

PMID- 11952880
TI  - Primary and secondary prevention in cardiovascular disease: an old-fashioned
      concept?
AB  - OBJECTIVE: Is the concept of primary and secondary cardiovascular prevention an
      old-fashioned concept that needs to be re-defined? DESIGN: Discussion paper.
      RESULTS: Cardiovascular prevention means reduction of absolute risk for
      cardiovascular disease (CVD), irrespective of clinical stage. CONCLUSION: For the
      calculation of an individual probability to develop CVD all factors that
      contribute to the risk must be taken into account, including previous CVD events.

PMID- 11952881
TI  - A rapid increase in beta-cell function by multiple insulin injections in type 2
      diabetic patients is not further enhanced by prolonging treatment.
AB  - OBJECTIVE: Intensive insulin treatment in type 2 diabetes can improve beta-cell
      function. It is not known which duration of treatment achieves maximal
      improvement. We addressed this question in type 2 diabetic patients who displayed
      features of 'secondary failure'. RESEARCH DESIGN AND METHOD: Ten patients were
      randomized to multiple insulin injection (MI) therapy for 9 weeks. Another 10
      patients started with bedtime insulin (BTI) and continued their peroral
      medication. Following 9 weeks of treatment, patients on MI switched to BTI and
      glibenclamide. RESULTS: Three days of MI led to a decrease in fasting
      proinsulin/insulin ratio, 0.43 +/- 0.20 vs. 0.29 +/- 0.11, P=0.01 and an increase
      in glucagon-stimulated C-peptide over baseline, 0.77 +/- 0.43 vs. 1.28 +/- 0.44
      nmol L-1, P 0.02. Nine weeks of MI treatment successively decreased fasting and
      nonfasting blood glucose in parallel with increasing insulin dosage. Initial
      improvements in secretion parameters were upheld but not further enhanced, the 9
      week proinsulin/insulin ratio being 99 +/- 23% and that of glucagon-stimulated C
      peptide being 95 +/- 24% of the values obtained after 3 days of treatment. Eight
      weeks after termination of MI there persisted a total weight gain that tended to
      be larger than after continuous peroral medication with BTI. CONCLUSION:
      Improvement of insulin secretion by intensive insulin treatment is rapidly gained
      with no further effect obtained after a longer treatment period. This finding, as
      well as undesirable effects of MI on body weight, argues against prolonged MI
      treatment as a prelude to other therapeutic regimens in type 2 diabetic patients.

PMID- 11952882
TI  - Prevalence of increased QT interval duration and dispersion in type 2 diabetic
      patients and its relationship with coronary heart disease: a population-based
      cohort.
AB  - OBJECTIVE: To evaluate the prevalence of prolonged QT interval and dispersion in
      a population-based cohort of type 2 diabetic patients and their relationship with
      clinical and metabolic variables. DESIGN: Cross-sectional population-based
      cohort. SETTING: Diabetes clinics and general practitioners in Casale Monferrato
      (Northern Italy). SUBJECTS: A total of 1357 patients with known type 2 diabetes
      (70% of the cohort). MAIN OUTCOMES MEASURES: Albumin excretion rate and coronary
      heart disease (CHD); a standard supine 12-lead electrocardiogram (ECG) was
      recorded and coded according to the Minnesota code criteria. QT interval
      corrected for heart rate (QTc) > 0.44 s and QTc dispersion > 0.080 s were
      considered abnormally prolonged. RESULTS: Prevalence of increased QTc duration
      and QTc dispersion were 25.8% (95% CI 23.5-28.3) and 33.1% (95% CI 30.6-35.7),
      with no sex differences. No metabolic differences were found, apart from
      fibrinogen and creatinine levels, which were higher in patients with increased
      QTc dispersion. Patients with CHD had higher mean adjusted values of QTc and QTc
      dispersion, whereas no association was found with albumin excretion rate (AER)
      and diabetes treatment. QTc duration and QTc dispersion were significantly
      correlated (0.17, P < 0.001). In multiple regression analysis, only CHD was
      independently associated with QTc, after adjustment for age and sex (beta=0.010,
      P < 0.001, R2=2.5%); as regards QTc dispersion, a similar association with CHD
      was found (beta=0.20, P < 0.001, R2=4.8%). CONCLUSIONS: This population-based
      study shows a considerably high prevalence of increased QTc and QTc dispersion in
      type 2 diabetic patients and their association with CHD. These findings have both
      epidemiological and clinical relevance, as they might be implicated in the excess
      mortality risk of type 2 diabetic patients.

PMID- 11952883
TI  - Cardiovascular prevention before admission reduces mortality following acute
      myocardial infarction in patients with diabetes.
AB  - OBJECTIVES: Previous studies have shown that patients with diabetes mellitus have
      an increased mortality after suffering from acute myocardial infarction (AMI).
      Patients with diabetes have several risk factors for cardiovascular disease. Our
      objective was to quantify the prevalence of pharmacological cardiovascular
      prevention at admission and relate such treatment to short and long-term
      mortality following AMI in patients with and without diabetes. DESIGN AND
      SUBJECTS: All patients discharged from the Department of Internal Medicine at
      Helsingborg Hospital in 1996 and 1997 with a principal diagnosis of AMI were
      included in the study. Patients were divided into two groups according to the
      presence or absence of diabetes. Cardiovascular risk factors, on-going
      medication, type of ward following admission, peak creatine kinase MB mass (CKMB)
      and immediate treatment were registered. Information about death was obtained
      from the national register. Kaplan-Meier analysis was performed for life
      expectancy. RESULTS: A total of 673 patients with AMI were registered, of which
      117 (17.4%) had diabetes. No differences in 30 days (17.1% vs. 15.3%) or 1-year
      (24.8% vs. 27.4%) mortality were seen between the diabetes and control groups,
      whereas the 2-year mortality was significantly higher in the diabetes group
      (40.2% vs. 29.1%). Cardiovascular risk factors occurred more often in the
      diabetes group and the use of aspirin, ACE-inhibitors, statins and diuretics was
      significantly more frequent. In patients treated with aspirin, in combination
      with either statin or angiotensin converting enzyme (ACE)-inhibitor, or both, no
      differences were seen in 30 days, 1 or 2-year mortality between groups.
      CONCLUSION: In contrast to earlier studies we did not find an increased 30 days
      and 1-year mortality in patients with diabetes suffering from AMI. This
      discrepancy was linked to a higher frequency of pharmacological cardiovascular
      prevention, a finding supporting the hypothesis that survival of a diabetes
      patient after AMI could be affected by factors operating before the infarction.

PMID- 11952884
TI  - Quality of life in patients with familial hypercholesterolaemia.
AB  - OBJECTIVES: The primary aim of this study was to analyse quality of life in adult
      patients with familial hypercholesterolaemia (FH), a genetic disorder with
      increased risk of coronary heart disease (CHD). Secondary aims were to find
      explanatory factors for quality of life and anxiety. DESIGN: A descriptive cross
      sectional design was used. SETTING: Outpatients from lipid clinics at two
      university hospitals in Sweden were included. Patients with heterozygous FH and a
      randomly selected control group participated by filling out questionnaires.
      SUBJECTS: Two hundred and eighty patients with heterozygous FH above 18 years of
      age were asked, and 212 of whom 185 were free of overt CHD, participated. Of a
      control group of 2980 persons 1485 were included for comparison. METHODS: We used
      Likert-type questionnaires: the Quality of Life Index (QLI) consisting of four
      subscales, the Hospital Anxiety and Depression Scale (HAD), the Mastery Scale
      measuring coping and a questionnaire on health and lipids constructed for FH
      patients. RESULTS: Patients with FH were significantly more satisfied with
      overall quality of life 21.8 +/- 0.3 (SEM) vs. controls 21.1 +/- 0.1 and this was
      also the case in three of four subscales, all differences P < 0.05. Anxiety about
      getting CHD was expressed amongst 86% of the patients with FH. CONCLUSIONS:
      Quality of life amongst patients with FH was at least as good as in controls but
      they were worried about getting CHD.

PMID- 11952885
TI  - Effects of simvastatin and atorvastatin on inflammation markers in plasma.
AB  - OBJECTIVES: To study the effect of statins on plasma markers for inflammation.
      DESIGN: Patients with hypercholesterolemia were randomized in one of the
      following treatments: Simvastatin (S) + placebo: S 40 mg for 6 weeks - S 80 mg
      for 6 weeks - S 80 mg for 24 weeks and Atorvastatin (A) + placebo: A 20 mg for 6
      weeks - A 40 mg for 6 weeks - A 80 mg for 24 weeks. SUBJECTS: Forty-seven
      patients with hypercholesterolemia were recruited in four different outpatient
      clinics. MAIN OUTCOME MEASURES: Samples were obtained at randomization after 6,
      12 and 36 weeks. Plasma or serum was analysed for lipids and for inflammation
      markers: C-reactive protein (CRP), serum amyloid A (SAA), soluble phospholipase
      A2 (SPLA2), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6).
      RESULTS: The reduction in LDL was similar for the two statins, except at the
      highest dose of atorvastatin (41 vs. 47%). The increase in HDL tended to be more
      pronounced in the simvastatin group, significantly so on the highest dose of
      atorvastatin (P < 0.05). CRP and SAA was significantly reduced by atorvastatin,
      whilst no reduction was seen for simvastatin. There was a significant difference
      in treatment effects between the two statins. Both statins caused a reduction in
      SPLA2. For IL-6 and ICAM-1 only small and inconsistent reductions were observed
      for both statins. CONCLUSION: Atorvastatin reduced the liver-derived acute-phase
      reactants, CRP and SAA, whilst the effect of simvastatin was small or absent.
      Small and inconsistent effects were seen for both statins on plasma levels of IL
      6 and ICAM-1.

PMID- 11952886
TI  - On the diagnosis of polycythaemia vera as assessed in the health and medical care
      in the Vastra Gotaland region, Sweden.
AB  - OBJECTIVES: The aim was to assess how the diagnosis of polycythaemia vera (PV)
      was established and to study to which extent the classic Polycythemia Vera Study
      Group (PVSG) criteria and the revised criteria for the diagnosis of PV as
      proposed by Pearson and Messinezy in 1996 (PM criteria) were fulfilled when the
      diagnosis of PV was made. DESIGN AND SETTING: A questionnaire was sent to
      physicians in charge of haematological patients at the departments of medicine in
      12 hospitals in the Health and Medical Care in the Vastra Gotaland Region (VGR),
      Sweden, with a population of 1.5 million inhabitants; they were asked to provide
      reports as regards all patients with an unequivocal diagnosis of PV during a 5
      year period from January 1994 to December 1998. SUBJECTS: Full reports were
      obtained from six hospitals, which serve about 1.1 million inhabitants. The
      results from a total of 129 PV patients, 62 from two university hospitals (UHs)
      and 67 from four county hospitals (CHs), were the subject of the present
      analysis. Results. It was shown that measurement of the red cell mass (RCM) had
      been carried out in 61 of 62 (98%) patients in UHs compared with 24 of 67 (36%)
      patients at CHs (P < 0.01). By using ultrasound imaging and/or scintigraphy the
      spleen size had been determined in 55 of 62 (89%) patients at UHs and in 24 of 67
      (36%) patients at CHs (P < 0.01). At the UHs, arterial oxygen saturation had been
      measured in 32 of 62 (52%) patients; the corresponding figure for the CH patients
      was 22 of 67 (33%). Plasma or serum erythropoietin (EPO) concentrations had been
      measured in 44 of 62 (71%) of PV patients at UHs and in 31 of 67 (46%) of
      patients at CHs; in all these cases the EPO concentrations were subnormal or not
      measurable. CONCLUSIONS: At the UHs only 37% of the PV patients fulfilled the
      PVSG criteria for the diagnosis of PV whereas the corresponding figure for CHs
      was 4% (P < 0.01). The adherence to PM criteria was, however, 71% at UHs compared
      with 16% at CHs (P < 0.01).

PMID- 11952887
TI  - Unusual case of a large midoesophageal diverticulum mimicking unstable angina
      pectoris.
AB  - We describe a 77-year-old lady who presented with progressive retrosternal pain
      radiating to the left arm and the back. After exclusion of cardiac causes a large
      midoesophageal diverticulum was found on oesophago-gastro-duodenoscopy.
      Importantly, the retrosternal pain completely disappeared after endoscopic
      removal of impacted food from the diverticulum. After the surgical resection the
      patient became fully asymptomatic. This is the first example of angina-like chest
      pain which definitively resulted from a midoesophageal diverticulum. Therefore,
      midoesophageal diverticula should be considered as a rare differential diagnosis
      of exercise-induced retrosternal pain.

PMID- 11952888
TI  - Can doxycycline cause polyneuropathy?

PMID- 11952889
TI  - Asymptomatic versus symptomatic persistent atrial fibrillation: clinical and
      noninvasive characteristics (Journal of Internal Medicine 2002; 250: 390-7).

PMID- 11952891
TI  - The yield of a diagnostic hospital dyspnoea clinic for the primary care section
      (Journal of Internal Medicine 2002; 250: 422-8).

PMID- 11952892
TI  - Staphylococcus and biofilms.
AB  - The genetic and molecular basis of biofilm formation in staphylococci is
      multifaceted. The ability to form a biofilm affords at least two properties: the
      adherence of cells to a surface and accumulation to form multilayered cell
      clusters. A trademark is the production of the slime substance PIA, a
      polysaccharide composed of beta-1,6-linked N-acetylglucosamines with partly
      deacetylated residues, in which the cells are embedded and protected against the
      host's immune defence and antibiotic treatment. Mutations in the corresponding
      biosynthesis genes (ica operon) lead to a pleiotropic phenotype; the cells are
      biofilm and haemagglutination negative, less virulent and less adhesive on
      hydrophilic surfaces. ica expression is modulated by various environmental
      conditions, appears to be controlled by SigB and can be turned on and off by
      insertion sequence (IS) elements. A number of biofilm-negative mutants have been
      isolated in which polysaccharide intercellular adhesin (PIA) production appears
      to be unaffected. Two of the characterized mutants are affected in the major
      autolysin (atlE) and in D-alanine esterification of teichoic acids (dltA).
      Proteins have been identified that are also involved in biofilm formation, such
      as the accumulation-associated protein (AAP), the clumping factor A (ClfA), the
      staphylococcal surface protein (SSP1) and the biofilm-associated protein (Bap).
      Concepts for the prevention of obstinate polymer-associated infections include
      the search for new anti-infectives active in biofilms and new biocompatible
      materials that complicate biofilm formation and the development of vaccines.

PMID- 11952893
TI  - A genome-wide strategy for the identification of essential genes in
      Staphylococcus aureus.
AB  - To address the need for new approaches to antibiotic drug development, we have
      identified a large number of essential genes for the bacterial pathogen,
      Staphylococcus aureus, using a rapid shotgun antisense RNA method. Staphylococcus
      aureus chromosomal DNA fragments were cloned into a xylose-inducible expression
      plasmid and transformed into S. aureus. Homology comparisons between 658 S.
      aureus genes identified in this particular antisense screen and the Mycoplasma
      genitalium genome, which contains 517 genes in total, yielded 168 conserved
      genes, many of which appear to be essential in M. genitalium and other bacteria.
      Examples are presented in which expression of an antisense RNA specifically
      reduces its cognate mRNA. A cell-based, drug-screening assay is also described,
      wherein expression of an antisense RNA confers specific sensitivity to compounds
      targeting that gene product. This approach enables facile assay development for
      high throughput screening for any essential gene, independent of its biochemical
      function, thereby greatly facilitating the search for new antibiotics.

PMID- 11952895
TI  - afsS is a target of AfsR, a transcriptional factor with ATPase activity that
      globally controls secondary metabolism in Streptomyces coelicolor A3(2).
AB  - AfsR is a pleiotropic, global regulator that controls the production of
      actinorhodin, undecylprodigiosin and calcium-dependent antibiotic in Streptomyces
      coelicolor A3(2). AfsR, with 993 amino acids, is phosphorylated on serine and
      threonine residues by a protein serine/threonine kinase AfsK and contains an OmpR
      like DNA-binding fold at its N-terminal portion and A- and B-type nucleotide
      binding motifs in the middle of the protein. The DNA-binding domain, in
      dependently of the nucleotide-binding domain, contributed the binding of AfsR to
      the upstream region of afsS that locates immediately 3' to afsR and encodes a 63
      amino-acid protein. No transcription of afsS in the DeltaafsR background and
      restoration of afsS transcription by afsR on a plasmid in the same genetic
      background indicated that afsR served as a transcriptional activator for afsS.
      Interestingly, the AfsR binding site overlapped the promoter of afsS, as
      determined by DNase I protection assay and high-resolution S1 nuclease mapping.
      The nucleotide-binding domain contributed distinct ATPase and GTPase activity.
      The phosphorylation of AfsR by AfsK greatly enhanced the DNA-binding activity and
      modulated the ATPase activity. The DNA-binding ability of AfsR was independent of
      the ATPase activity. However, the ATPase activity was essential for
      transcriptional activation of afsS, probably because the energy available from
      ATP hydrolysis is required for the isomerization of the closed complex between
      AfsR and RNA polymerase to a transcriptionally competent open complex. Thus, AfsR
      turns out to be a unique transcriptional factor, in that it is modular, in which
      DNA-binding and ATPase activities are physically separable, and the two functions
      are modulated by phosphorylation on serine and threonine residues.

PMID- 11952894
TI  - Truncation of merozoite surface protein 3 disrupts its trafficking and that of
      acidic-basic repeat protein to the surface of Plasmodium falciparum merozoites.
AB  - Merozoite surface protein 3 (MSP3), an important vaccine candidate, is a soluble
      polymorphic antigen associated with the surface of Plasmodium falciparum
      merozoites. The MSP3 sequence contains three blocks of heptad repeats that are
      consistent with the formation of an intramolecular coiled-coil. MSP3 also
      contains a glutamic acid-rich region and a putative leucine zipper sequence at
      the C-terminus. We have disrupted the msp3 gene by homologous recombination,
      resulting in the expression of a truncated form of MSP3 that lacks the putative
      leucine zipper sequence but retains the glutamic acid-rich region and the heptad
      repeats. Here, we show that truncated MSP3, lacking the putative leucine zipper
      region, does not localize to the parasitophorous vacuole or interact with the
      merozoite surface. Furthermore, the acidic-basic repeat antigen (ABRA), which is
      present on the merozoite surface, also was not localized to the merozoite surface
      in parasites expressing the truncated form of MSP3. The P. falciparum merozoites
      lacking MSP3 and ABRA on the surface show reduced invasion into erythrocytes.
      These results suggest that MSP3 is not absolutely essential for blood stage
      growth and that the putative leucine zipper region is required for the
      trafficking of both MSP3 and ABRA to the parasitophorous vacuole.

PMID- 11952896
TI  - Spc24 interacts with Mps2 and is required for chromosome segregation, but is not
      implicated in spindle pole body duplication.
AB  - Mps2 (monopolar spindle protein) is a coiled-coil protein found at the spindle
      pole body (SPB) and at the nuclear envelope that is required for insertion of the
      SPB into the nuclear envelope. We identified three proteins that interact with
      Mps2 in a two-hybrid screen: Bbp1, Ynl107w and Spc24. All three proteins contain
      coiled-coil motifs that appear to be required for their interaction with Mps2. In
      this work, we verified the Mps2-Spc24 interaction by co-immunoprecipitation in
      vivo and by the in vitro interaction of recombinant proteins. Previous two-hybrid
      screens with Spc24 as bait had identified Spc25 and Ndc80 as putative interacting
      partners, and we verified these interactions in vivo by purification of TAP
      tagged derivatives of Spc24 and Ndc80. Finally, we found that spc24
      thermosensitive mutants had a chromosome segregation defect, but no apparent
      defect in SPB duplication. These results are consistent with recently published
      data showing that Spc24, Spc25 and Ndc80 are peripheral kinetochore com-ponents
      required for chromosome segregation. The Mps2-Spc24 interaction may contribute to
      the localization of Spc24 and other kinetochore components to the inner plaque of
      the SPB.

PMID- 11952897
TI  - RNase G complementation of rne null mutation identifies functional
      interrelationships with RNase E in Escherichia coli.
AB  - The Escherichia coli endoribonucleases RNase E (Rne) and RNase G (Rng) have
      sequence similarity and broadly similar sequence specificity. Whereas the absence
      of Rne normally is lethal, we show here that E. coli bacteria that lack the rne
      gene can be made viable by overexpression of Rng. Rng-complemented cells
      accumulated precursors of 5S ribosomal RNA (rRNA) and the RNA component of RNase
      P (i.e. M1 RNA), indicating that normal processing of these Rne-cleaved RNAs was
      not restored by RNase G; additionally, neither 5S rRNA nor M1 RNA was generated
      from precursors by RNase G cleavage in vitro. Using DNA microarrays containing
      4405 Escherichia coli open reading frames (ORFs), we identified mRNAs whose
      steady-state level was affected by Rne, Rng or the N-terminal catalytic domain of
      RNase E. Most transcript species affected by RNase E deficiency were also
      elevated in an rne deletion mutant complemented by Rng. However, approximately
      100 mRNAs that accumulated in Rne-deficient cells were decreased by rng
      complemention, thus identifying targets whose processing or degradation may be
      the basis for RNase E essentiality. Remarkably prominent in this group were mRNAs
      implicated in energy-generating pathways or in the synthesis or degradation of
      macromolecules.

PMID- 11952898
TI  - Functional complexity of the twin-arginine translocase TatC component revealed by
      site-directed mutagenesis.
AB  - The Escherichia coli Tat apparatus is a membrane-bound protein translocase that
      serves to export folded proteins synthesized with N-terminal twin-arginine signal
      peptides. The essential TatC component of the Tat translocase is an integral
      membrane protein probably containing six transmembrane helices. Sequence analysis
      identified conserved TatC amino acid residues, and the role of these side-chains
      was assessed by single alanine substitution. This approach identified three
      classes of TatC mutants. Class I mutants included F94A, E103A and D211A, which
      were completely devoid of Tat-dependent protein export activity and thus
      represented residues essential for TatC function. Cross-complementation
      experiments with class I mutants showed that co-expression of D211A with either
      F94A or E103A regenerated an active Tat apparatus. These data suggest that
      different class I mutants may be blocked at different steps in protein transport
      and point to the co-existence of at least two TatC molecules within each Tat
      translocon. Class II mutations identified residues important, but not essential,
      for Tat activity, the most severely affected being L99A and Y126A. Class III
      mutants showed no significant defects in protein export. All but three of the
      essential and important residues are predicted to cluster around the cytoplasmic
      N-tail and first cytoplasmic loop regions of the TatC protein.

PMID- 11952899
TI  - Identification of novel factors involved in colonization and acid tolerance of
      Vibrio cholerae.
AB  - Despite over 100 years of study, the intestinal pathogen Vibrio cholerae still
      causes epidemic disease in areas of the world where there is poor sanitation.
      While cholera toxin and the toxin-coregulated pilus (TCP) are known to be
      essential for full virulence, the role that other factors play has remained ill
      defined. Herein, we describe a large-scale signature-tagged mutagenesis (STM)
      screen utilizing 100 pools of 96 mutants each to identify factors involved in
      colonization of the infant mouse small intestine. A total of 164 mutants
      representing transposition events into 95 different open reading frames were
      shown to be recovered at greatly reduced numbers from the infant mouse model.
      Analysis of the sites of insertion revealed multiple independent mutations within
      the rfb gene cluster, needed for synthesis of lipopolysaccharide (LPS), and the
      tcp gene cluster, needed for synthesis of the TCP. More importantly, in addition
      to these previously known colonization factors, we identified many genes whose
      activity in colonization was not previously appreciated. These can be divided
      into a number of functional groups, which include production of factors involved
      in metabolic activities, regulation of cellular processes, transport, adaptation
      to stress and unknown functions. In addition, we describe the reiterative use of
      STM, whereby colonization-defective mutants were assembled into virulence
      attenuated pools (VAPs), which were used to begin to reveal roles that the
      identified virulence factors play in the infection process. Nine new factors were
      shown to be crucial for the V. cholerae acid tolerance response, which has
      previously been hypothesized to be important for epidemic spread of cholera.
      Competition assays of these nine acid tolerance response (ATR)-defective mutants
      revealed that mutations in gshB, hepA and recO result in a 1000-fold reduction in
      colonization.

PMID- 11952900
TI  - OmpR-dependent and OmpR-independent responses of Escherichia coli to sublethal
      attack by the neutrophil bactericidal/permeability increasing protein.
AB  - Bactericidal/permeability-increasing protein (BPI) of neutrophils is a
      lipopolysaccharide (LPS)-binding antibacterial protein with specificity for Gram
      negative bacteria. BPI binding to the bacterial surface rapidly triggers
      potentially reversible bacterial growth inhibition and alterations of the outer
      membrane and, later, disruption of the inner membrane and lethal injury. Initial
      effects include selective OmpR-dependent changes in the synthesis of outer
      membrane porins (OmpF and OmpC). Because OmpR is a global transcriptional
      regulator, we have examined its possible role in responses of E. coli to
      sublethal injury caused by BPI. Early (<15 min) reversible effects of BPI on
      bacterial colony-forming ability and outer membrane permeability were virtually
      identical in isogenic wild-type (wt) and ompR- E. coli. Both strains could repair
      the outer membrane permeability barrier after Mg2+-induced displacement of bound
      BPI. However, OmpR was essential for the ability of E. coli to tolerate low doses
      of BPI and escape the progression of sublethal to lethal damage. Scanning
      electron microscopy revealed that BPI treatment produced greater membrane
      perturbations in the ompR- strain, apparent even before lethal injury. These
      findings suggest that the fate of E. coli exposed to BPI depends on both OmpR
      independent mechanisms engaged in outer membrane repair and OmpR- dependent
      processes that modulate porin synthesis and retard progression of injury from the
      outer to the inner membrane.

PMID- 11952901
TI  - Immediate GTP hydrolysis upon FtsZ polymerization.
AB  - To understand the polymerization dynamics of FtsZ, a bacterial cell division
      protein similar to tubulin, insight is required into the nature of the nucleotide
      bound to the polymerized protein. In a previous study, we showed that the FtsZ
      polymers contain mostly GDP. A recent study challenged this result, suggesting
      that the polymerized FtsZ is in a GTP-bound state. Here, we show that, when
      radiolabelled [gamma-32P]-GTP is used to polymerize FtsZ, GTP is hydrolysed
      instantaneously. The FtsZ polymer contains both GDP and the radiolabelled
      inorganic phosphate.

PMID- 11952902
TI  - Polar location and functional domains of the Agrobacterium tumefaciens DNA
      transfer protein VirD4.
AB  - Agrobacterium tumefaciens VirD4 is essential for DNA transfer to plants. VirD4
      presumably functions as a coupling factor that facilitates communication between
      a substrate and the transport pore. To serve as a coupling protein, VirD4 may be
      required to localize near the transport apparatus. In a previous study, we
      observed that several constituents of the transport apparatus localize to the
      cell membranes. In this study, we demonstrate that VirD4 has a unique cellular
      location. In immunofluorescence microscopy, cells probed with anti-VirD4
      antibodies had foci of fluorescence primarily at the cell poles, indicating that
      VirD4 localizes to the cell pole. Polar location of VirD4 was not dependent on T
      DNA processing, the formation of the transport apparatus and the presence of
      other Vir proteins. VirD4 is an integral membrane protein with one periplasmic
      domain. The large cytoplasmic region contains a nucleotide-binding domain. To
      investigate the role of these domains in DNA transfer, we introduced mutations in
      virD4 and studied the effect of a mutation on substrate transfer. A deletion of
      most of the periplasmic domain as well as the alterations of glycine 151 to
      serine and lysine 152 to alanine led to the complete loss of DNA transfer,
      indicating that both domains are essential for substrate transfer. Subcellular
      localization of the mutant proteins indicated that both the periplasmic and the
      nucleotide-binding domains are required for polar localization of VirD4. The
      periplasmic domain mutant VirD4Delta36-61 was distributed throughout the cell
      membrane, whereas the nucleotide binding site mutant VirD4G151S localized to
      sites other than the cell poles. Polar location of VirD4 suggests a role for the
      cell pole in DNA transfer.

PMID- 11952903
TI  - Spa15 of Shigella flexneri, a third type of chaperone in the type III secretion
      pathway.
AB  - The type III secretion (TTS) pathway is used by numerous Gram-negative pathogens
      to inject virulence factors into eukaryotic cells. In addition to a functional
      TTS apparatus, secretion of effector proteins depends upon specific chaperones.
      Using a two-hybrid screen in yeast and a co-purification assay in Shigella
      flexneri, we demonstrated that Spa15, which is encoded by an operon for
      components of the TTS apparatus, is associated in the cytoplasm with three
      proteins that are secreted by the TTS pathway, IpaA, IpgB1 and OspC3. Spa15 was
      found to be necessary for stability of IpgB1 but not IpaA, and for secretion of
      IpaA molecules that were stored in the cytoplasm but not those that were
      synthesized while the secretion apparatus was active. The ability of Spa15 to
      associate with several non-homologous secreted proteins, the presence of Spa15
      homologues in other TTS systems and the location of the corresponding genes
      within operons for components of the TTS apparatus suggest that Spa15 belongs to
      a new class of TTS chaperones.

PMID- 11952904
TI  - Down-regulation of pili and capsule of Neisseria meningitidis upon contact with
      epithelial cells is mediated by CrgA regulatory protein.
AB  - The initial attachment of Neisseria meningitidis to the target cell surface
      appears to be largely pilus depend-ent in capsulated bacteria. Intimate adhesion
      subsequently occurs to permit colonization. We recently reported that insertional
      inactivation of the crgA gene, which encodes a transcriptional regulator
      belonging to the LysR family, decreased meningococcal adhesion to epithelial
      cells and abolished intimate adhesion. In this report, we analyse expression of
      the pilE and sia genes, which are involved in the biosynthesis of pili and
      capsule respectively, during bacteria-host cell interactions. Western blotting,
      transcriptional fusion and reverse transcriptase polymerase chain reaction (RT
      PCR) analysis showed that the expression of these genes was downregulated during
      intimate adhesion. DNA-binding assays, footprinting and RT-PCR analysis indicated
      that this downregulation was directly mediated by the CrgA protein. The pilE and
      sia promoters were found to have a CrgA binding motif in common. These results
      strongly suggest that N. meningitidis displays an adaptive response upon cell
      contact. CrgA may play a central regulatory role in meningococcal adhesion,
      particularly in switching from initial to intimate adhesion by downregulating the
      bacterial surface structures that hinder this adhesion.

PMID- 11952905
TI  - Identification of genes that are associated with DNA repeats in prokaryotes.
AB  - Using in silico analysis we studied a novel family of repetitive DNA sequences
      that is present among both domains of the prokaryotes (Archaea and Bacteria), but
      absent from eukaryotes or viruses. This family is characterized by direct
      repeats, varying in size from 21 to 37 bp, interspaced by similarly sized non
      repetitive sequences. To appreciate their characteri-stic structure, we will
      refer to this family as the clustered regularly interspaced short palindromic
      repeats (CRISPR). In most species with two or more CRISPR loci, these loci were
      flanked on one side by a common leader sequence of 300-500 b. The direct repeats
      and the leader sequences were conserved within a species, but dissimilar between
      species. The presence of multiple chromosomal CRISPR loci suggests that CRISPRs
      are mobile elements. Four CRISPR-associated (cas) genes were identified in CRISPR
      containing prokaryotes that were absent from CRISPR-negative prokaryotes. The cas
      genes were invariably located adjacent to a CRISPR locus, indicating that the cas
      genes and CRISPR loci have a functional relationship. The cas3 gene showed motifs
      characteristic for helicases of the superfamily 2, and the cas4 gene showed
      motifs of the RecB family of exonucleases, suggesting that these genes are
      involved in DNA metabolism or gene expression. The spatial coherence of CRISPR
      and cas genes may stimulate new research on the genesis and biological role of
      these repeats and genes.

PMID- 11952907
TI  - Two DNA-binding domains of Mga are required for virulence gene activation in the
      group A streptococcus.
AB  - Mga is a DNA-binding protein that activates expression of several important
      virulence genes in the group A streptococcus (GAS), including those encoding M
      protein (emm), C5a peptidase (scpA) and Mga (mga). To determine the functionality
      of four potential helix-turn-helix DNA-binding motifs (HTH1-HTH4) identified
      within the amino-terminus of Mga, alanine substitutions were introduced within
      each domain in a MBP-Mga fusion allele and purified proteins were assayed for
      binding to Mga-specific promoter fragments (Pmga, PscpA and Pemm) in vitro.
      Although HTH-1 and HTH-2 mutations showed wild type DNA-binding activity, an
      altered HTH-3 domain resulted in reduced binding to the three promoters and an
      HTH-4 mutant was devoid of detectable binding activity. Plasmid-encoded
      expression of the HTH-3 and HTH-4 alleles from a constitutive promoter (Pspac) in
      the mga-deleted GAS strain JRS519 demonstrated that Mga-regulated emm expression
      correlated directly to the DNA-binding activity observed for each mutant protein
      in vitro. Single-copy expression of HTH-3 and HTH-4 from their native Pmga
      resulted in a dramatic reduction in autoregulated mga expression in both mutant
      strains. Thus, Mga appears to contain two DNA-binding domains (HTH-3 and HTH-4)
      that are required for direct activation of the Mga virulence regulon in vivo.

PMID- 11952906
TI  - ToxR interferes with CRP-dependent transcriptional activation of ompT in Vibrio
      cholerae.
AB  - In pathogenic Vibrio cholerae, the transmembrane DNA-binding protein ToxR co
      ordinates the expression of over 20 genes, including those encoding important
      virulence factors such as cholera toxin and the toxin-co-regulated pilus. The
      outer membrane protein OmpT is the only member of the ToxR regulon known to be
      repressed by ToxR. In this study, we examined the environmental conditions that
      regulate OmpT expression and demonstrated that ompT transcription is upregulated
      14-fold when the bacteria enter late log phase from early log phase. Deletion of
      the crp gene completely abolishes OmpT expression. Comparison of ompT
      transcription levels in the isogenic crp-, toxR- and crp-toxR- mutants revealed
      that (i) in the absence of ToxR, constitutive high-level ompT transcription is
      dependent on cAMP receptor protein (CRP); (ii) ToxR not only interferes with CRP
      dependent ompT activation, but also abolishes the CRP-independent, basal level
      ompT transcription; thus, the mechanism by which ToxR represses ompT
      transcription involves both antiactivation and direct repression; (iii) both CRP
      and ToxR are required for the regulation of OmpT expression by growth phase. To
      provide further insights into the molecular mecha-nism of CRP-dependent
      activation of ompT transcription, we demonstrated that CRP-dependent activation
      requires a CRP binding site centred at -310 of the ompT promoter, without which
      the interaction of CRP with other CRP binding site(s) more proximal to the
      promoter results in repression. Mutations in two regions on CRP (AR1 and AR2)
      that directly contact RNA polymerase (RNAP) abolish activation, suggesting direct
      interaction of CRP with RNAP from -310 of the ompT promoter via DNA looping.

PMID- 11952908
TI  - Transferrin binding in Staphylococcus aureus: involvement of a cell wall-anchored
      protein.
AB  - The ability to gain access to iron is pivotal for bacterial pathogens during
      infection. Although much is known about iron acquisition systems in Gram-negative
      bacteria, comparatively little is known about how Gram-positive pathogens access
      iron from host iron sources. A previous study showed that, in the Gram-positive
      human pathogen Staphylococcus aureus, a cell surface-associated glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) enzyme (Gap, or Tpn) is capable of binding human
      transferrin, representing a potential means by which this bacterium is able to
      access iron in vivo. We have investigated this property of S. aureus further and
      shown that, in S. aureus RN6390, GAPDH is expressed on the S. aureus cell surface
      independent of exogenous iron concentrations, and that overexpressed and purified
      Gap, although retaining GAPDH activity, has no affinity for human transferrin.
      Moreover, although a S. aureus gap mutant was devoid of surface-associated and
      cytoplasmic GAPDH activity, it retained the ability to bind human transferrin,
      equivalent to wild type. We concluded from these results that the Gap protein is
      not involved in S. aureus binding to human transferrin. We identified the
      transferrin-binding protein as a novel cell wall-anchored protein, designated
      StbA for staphylococcal transferrin-binding protein A, which shared no
      significant similarities with any other bacterial transferrin-binding proteins.
      StbA contained a C-terminal cell wall-anchoring motif (LPKTG), and expression of
      StbA in the cell wall was strictly controlled by exogenous iron concentrations.
      The stbA gene is found within a 7 kb region in the S. aureus chromosome that
      contains a total of six iron-regulated genes. Immediately downstream from stbA is
      an iron-regulated gene whose product was predicted to be another cell wall
      anchored protein with no significant similarity to proteins with characterized
      functions. Transcribed in the opposite direction from stbA is a four-gene operon
      whose expression is also regulated by iron. While the deduced products of the
      first two genes lack similarity to known proteins, the last two genes encode,
      respectively, putative lipoprotein and permease components of an ABC transporter
      that shares significant similarities with several iron(III) ABC transporters in a
      variety of bacteria.

PMID- 11952909
TI  - Developmental switch of S-layer protein synthesis in Bacillus anthracis.
AB  - Adjustment of the synthesis of abundant protein to the requirements of the cell
      involves processes critical to the minimization of energy expenditure. The
      regulation of S-layer genes might be a good model for such processes because
      expression must be controlled, such that the encoded proteins exactly cover the
      surface of the bacterium. Bacillus anthracis has two S-layer genes, sap and eag,
      encoding the S-layer proteins Sap and EA1 respectively. We report that the
      production and surface localization of Sap and EA1 are under developmental
      control, suggesting that an exponential phase 'Sap layer' is subsequently
      replaced by a stationary phase 'EA1 layer'. This switch is controlled at the
      transcriptional level: sap is most certainly transcribed by RNA polymerase
      containing sigmaA, whereas eag expression depends on sigmaH. More importantly,
      Sap is required for the temporal control of eag, and EA1 is involved in strict
      feedback regulation of eag. This control may be direct because both S-layer
      proteins bind, in vitro, the eag promoter, specifically suggesting that they
      might act as transcriptional repressors.

PMID- 11952910
TI  - The proper folding of a long C-terminal segment of the yeast Lys14p regulator is
      required for activation of LYS genes in response to the metabolic effector.
AB  - Transcription of lysine genes in Saccharomyces cerevisiae is dependent on Lys14p
      and on alpha-aminoadipate semialdehyde (alphaAASA), an intermediate of the
      pathway. The two-thirds C-terminal end of Lys14p is sufficient to ensure the
      activation function of the protein and its modulation by alphaAASA. Here, we show
      that no single discrete domain of Lys14p is able to activate transcription and
      that most of the deleted LexA-Lys14p proteins are inactive even in the presence
      of a high alphaAASA concentration. The point mutations abolishing the activation
      capacity of Lys14p are distributed all over the entire C-terminal segment.
      Although the deletion of 20 residues rich in leucine and located downstream of
      the DNA-binding domain converts Lys14p to a constitutive transcriptional
      activator, our analysis provides evidence that the modulation process of Lys14p
      activity does not involve an effector-dependent masking/unmasking mechanism.
      Furthermore, we show that the protein chaperone Hsp82p is required for full
      activation of LYS genes by the alphaAASA-activated Lys14p as well as by the
      constitutive Lys14p. Our results suggest that the proper folding of the two
      thirds C-terminal portion of Lys14p is essential not only to activate
      transcription but also to modulate it according to alphaAASA concentration.

PMID- 11952911
TI  - The mismatch repair system (mutS, mutL and uvrD genes) in Pseudomonas aeruginosa:
      molecular characterization of naturally occurring mutants.
AB  - We have recently described the presence of a high proportion of Pseudomonas
      aeruginosa isolates (20%) with an increased mutation frequency (mutators) in the
      lungs of cystic fibrosis (CF) patients. In four out of 11 independent P.
      aeruginosa strains, the high mutation frequency was found to be complemented with
      the wild-type mutS gene from P. aeruginosa PAO1. Here, we report the cloning and
      sequencing of two additional P. aeruginosa mismatch repair genes and the
      characterization, by complementation of deficient strains, of these two putative
      P. aeruginosa mismatch repair genes (mutL and uvrD). We also describe the
      alterations in the mutS, mutL and uvrD genes responsible for the mutator
      phenotype of hypermutable P. aeruginosa strains isolated from CF patients. Seven
      out of the 11 mutator strains were found to be defective in the MMR system (four
      mutS, two mutL and one uvrD). In four cases (three mutS and one mutL), the genes
      contained frameshift mutations. The fourth mutS strain showed a 3.3 kb insertion
      after the 10th nucleotide of the mutS gene, and a 54 nucleotide deletion between
      two eight nucleotide direct repeats. This deletion, involving domain II of MutS,
      was found to be the main one responsible for mutS inactivation. The second mutL
      strain presented a K310M mutation, equivalent to K307 in Escherichia coli MutL, a
      residue known to be essential for its ATPase activity. Finally, the uvrD strain
      had three amino acid substitutions within the conserved ATP binding site of the
      deduced UvrD polypeptide, showing defective mismatch repair activity.
      Interestingly, cells carrying this mutant allele exhibited a fully active UvrABC
      mediated excision repair. The results shown here indicate that the putative P.
      aeruginosa mutS, mutL and uvrD genes are mutator genes and that their alteration
      results in a mutator phenotype.

PMID- 11952912
TI  - Studies on the role of the metK gene product of Escherichia coli K-12.
AB  - We show here that the metK gene is essential to the growth of Escherichia coli K
      12 and can be deleted only in the presence of a rescue plasmid carrying a
      functional metK gene. When metK expression was limited, genomic DNA methylation
      decreased and cell division was hampered. Through primer extension, the
      transcription start site of metK was located at 140 bp upstream of the
      translation start site. The frequently used metK84 mutant has been shown to carry
      an A(r)G transition in the -10 region of the metK promoter. This accounts for its
      low level of S-adenosylmethionine (SAM) synthetase and SAM deficiency.

PMID- 11952913
TI  - Bacterial resistance evolution by recruitment of super-integron gene cassettes.
AB  - The capture and spread of antibiotic resistance determinants by integrons
      underlies the rapid evolution of multiple antibiotic resistance among diverse
      Gram-negative clinical isolates. The association of multiple resistance integrons
      (MRIs) with mobile DNA elements facilitates their transit across phylogenetic
      boundaries and augments the potential impact of integrons on bacterial evolution.
      Recently, ancestral chromosomal versions, the super-integrons (SIs), were found
      to be genuine components of the genomes of diverse bacterial species. SIs possess
      evolutionary characteristics and stockpiles of adaptive functions, including
      cassettes related to antibiotic resistance determinants previously characterized
      in clinical isolates, which suggest that MRIs and their resistance genes were
      originally recruited from SIs and their pool of amassed genes. However, the
      recombination activity of integrons has never been demonstrated in a bacterium
      other than Escherichia coli. We introduced a naturally occurring MRI (TpR, SulR)
      on a conjugative plasmid into Vibrio cholerae, a species known to harbour a SI.
      We show that MRIs can randomly recruit genes directly from the cache of SI
      cassettes. By applying a selective constraint for the development of antibiotic
      resistance, we demonstrate bacterial resistance evolution through the recruitment
      a novel, but phenotypically silent, chloramphenicol acetyltransferase gene from
      the V. cholerae SI and its precise insertion into the MRI. The resulting
      resistance profile (CmR, TpR, SulR) could then be disseminated by conjugation to
      other clinically relevant pathogens at high frequency. These results demonstrate
      that otherwise phenotypically sensitive strains may still be a genetic source for
      the evolution of resistance to clinically relevant antibiotics through integron
      mediated recombination events.

PMID- 11952914
TI  - Self-esteem and mental health characteristics especially among lean students
      surveyed by University Personality Inventory.
AB  - In recent years, various investigators have indicated an increase in the number
      of eating disorders. A similar tendency has been observed among university
      students. The purpose of the present study is to clarify the self-esteem and
      mental health characteristics of the lean students who suffer from latent eating
      disorders. We examined 2132 responses to the University Personality Inventory
      obtained from students who entered Nagoya University in 1995. We analyzed the
      mental health conditions of the lean students after categorizing the subjects
      into lean, normal and obese group by body mass index. As a result, the following
      results were obtained. Lean male students presented with more subjective symptoms
      than normal and obese students, and extremely lean male students had more
      subjective symptoms. Lean female students had fewer subjective symptoms than lean
      male students and no particular differences from normal female students. It is
      suggested that male and female students had different criteria for self-esteem
      with regard to body shape. The lean female students were medically ill and formed
      a latent or borderline latent group with anorexia nervosa. However, they had a
      similar degree of health awareness as normal students.

PMID- 11952915
TI  - Elbow flexion response as another primitive reflex.
AB  - In daily clinical practice we noticed that patients with intellectual impairment
      spontaneously flex the elbow within a few seconds of the forearm being
      manipulated during routine examination of spasticity of the muscles in the upper
      extremities. We termed this phenomenon elbow flexion response (EFR), and
      prospectively studied it in 229 patients who underwent in-hospital rehabilitation
      following brain damage. Evaluation of each patient included EFR, patient profile,
      ability to communicate, scores on three parameters from various intelligence
      tests, scores on seven parameters testing primitive reflexes, and scores on three
      parameters describing personality. We investigated for relationships among these
      parameters. Consequently, although EFR rarely have a statistical association with
      the varied profiles of patients, patients with bilateral lesion or bilateral
      paresis demonstrated significantly more marked EFR than those with unilateral
      lesion or unilateral paresis. Patients with involvement of the frontal lobe
      showed significantly more marked EFR than those without damage in this area.
      Elbow flexion responses occurred significantly more frequently in relation with
      lower scores on intelligence and occurred with significantly higher frequency in
      conjunction with the more marked appearance of conventional primitive reflexes.
      Therefore, we conclude that EFR have a strong association with intelligence and
      with the existence of frontal lobe lesion, and their mode of clinical
      presentation parallels that of primitive reflexes particularly that of the grasp
      reflex. We propose that EFR could be referred as a variation of the grasp reflex
      occurring in the more proximal or axial part of the body.

PMID- 11952916
TI  - Psychiatric morbidity and pregnancy outcome in a disaster area of Taiwan 921
      earthquake.
AB  - We investigated the prevalence of minor psychiatric morbidity in a group of women
      who were pregnant during or immediately after a major earthquake disaster and we
      investigated the prognostic factors that may have influenced the perinatal
      outcome of the pregnancy. The study was initiated 6 months after the earthquake
      and enrolled 171 women in a town near the epicentre. A Post-Earthquake
      Questionnaire, Chinese Health Questionnaire (CHQ-12) and posttraumatic stress
      disorder (PTSD) symptoms checklist were completed before delivery while the
      perinatal data were retrieved from hospital obstetrical records. The prevalence
      of minor psychiatric morbidity (MPM) was 29.2%. Women with starvation experience,
      higher negative attitude scores about the influence of earthquake on pregnancy
      and more casualties among relatives were significantly correlated with high CHQ.
      A significant positive correlation between the MPM and PTSD scores was noticed.
      Among the 115 pregnancies with known perinatal outcome, there were nine (7.8%)
      low-birth weight neonates, defined as birth weight < or = 2500 g. Maternal
      history of abdominal injury, spouse casualty and instability in living condition
      were significantly correlated with low birth weight. Spouse casualty was the only
      significant factor that predicts neonatal low birth weight.

PMID- 11952917
TI  - Cognitive resource model for the information-processing of task-irrelevant visual
      stimuli.
AB  - In order to elucidate possible factors that effect P3s to task-irrelevant visual
      stimuli (non-target P3s), we made a normative visual event-related potential
      study with button-press tasks in four different conditions in which two factors
      (the number of colors of non-target stimuli, and the shape of the stimuli) were
      manipulated without any change in task nor target/non-target ratio. The peak
      distributions of non-target P3s (centrally peaking) were significantly different
      from those of task-relevant P3s (parietally peaking) in all conditions. The
      amplitude of non-target P3 decreased as the variety of colors of the non-target
      stimuli increased. The amplitude of non-target P3 to colored solid circles was
      larger than that of non-target P3 to colored Stroop stimuli. Between each
      condition, task- relevant P3 and reaction time showed no significant difference.
      Both the variety of non-target stimuli and the shape of the stimuli were shown to
      have effects on the amplitudes of non-target P3s without any alteration in task
      relevant P3s. It is suggested that the amplitude behaviors of non-target P3s
      partly reflect the amount of cognitive resource allocated for each different kind
      of task-irrelevant visual stimuli.

PMID- 11952918
TI  - Relationship of criminality to endogeneity and anxiety in patients with unipolar
      depression.
AB  - The relationship between criminal behavior on the one hand and endogeneity and
      anxiety on the other hand was investigated in a sample of patients with unipolar
      depression to help elucidate factors influencing the criminality rate in this
      population. A lower criminality rate in patients with higher ratings of
      endogeneity and anxiety was predicted. Clinical records of 179 male and 99 female
      psychiatric inpatients were retrospectively evaluated using the Newcastle Scale
      II and Hamilton Anxiety Scale. A full account of conviction records served as a
      measure of criminal behavior. Forty per cent of male patients and 7% of female
      patients were criminally registered. A lower criminality rate was indeed found in
      male and female patients with endogenous type of depression and in male patients
      with higher anxiety ratings. In a multivariate evaluation, however,
      sociodemographic variables in terms of age and social class seem to be more
      important predictors of criminality and all variables we assessed contributed
      only marginally to the explanation of the criminality variance. Thus, in patients
      with unipolar depression, sociodemographic factors seem to be of a greater even
      though still limited importance regarding criminal behavior compared with the
      clinical variables of endogeneity and anxiety.

PMID- 11952919
TI  - Pain threshold and pain recovery after experimental stimulation in patients with
      burning mouth syndrome.
AB  - The aim of the present study was to examine pain threshold and pain recovery in
      patients with burning mouth syndrome (BMS) and matched no-pain controls. Twenty
      female patients diagnosed with BMS without organic gross changes were enrolled in
      the study. Twenty control subjects were chosen from age-matched healthy female
      volunteers. We compared the thermal pain threshold using heat beam dolorimeter on
      the finger and tongue between patients and controls. Warm (at 50 degrees C for 5
      s), cold (at 0 degrees C for 30 s) and mechanical (stimulation by electric tooth
      brush for 15 s) stimulation was applied to the tongue for both groups.
      Participants were asked to rate the subjective pain using a visual analogue scale
      (VAS). Although there was no significant differences between patients and
      controls in terms of the threshold on the finger, the threshold on the tongue was
      significantly higher in patients than in controls. We suggest there were
      peripheral dysfunction at the tongue, and/or central dysfunction in patients with
      BMS. Among the three types of stimulation, the patients perceived significantly
      the highest pain from the mechanical stimulation for the first 5 min after the
      stimulation. Furthermore, when patients with BMS perceived some pain, they
      continued to complain of the pain longer and more intricately than the controls.
      This indicates that the pain of the patients is strongly affected not only at a
      sensory component but also at an affective/motivational component than the
      controls. However, we should be cautious of simply advancing psychogenic theory
      in this etiology.

PMID- 11952920
TI  - Precedents of perceived social support: personality, early life experiences and
      gender.
AB  - The perception of social support may be a trait-like construct stemming from the
      current personality and early environment as well as a summation of the actual
      support perceived. A total of 220 community individuals were examined for the
      effects of Eysenck Personality Questionnaire (EPQ) items and early life
      experience at home and outside on the number of sources of perceived social
      support and satisfaction with that support. High extraversion and low neuroticism
      scores of the EPQ were correlated with the availability of support only in women,
      while high maternal care and low maternal overprotection in childhood were
      correlated with the satisfaction with support only in men. Availability of
      support was also correlated with some types of early life events. The quantity
      and quality of perception of social support differ in their links to personality
      and early environment, and may be, to some extent, explainable in terms of them.

PMID- 11952921
TI  - Report on IL-10 gene polymorphism at position -819 for major depression and
      schizophrenia in Korean population.
AB  - The present study was carried out to examine the relationship of interleukin (IL)
      10 gene polymorphism at position -819 for major depression and schizophrenia in
      the Korean population. DNA was extracted from 92 Korean patients with major
      depression, 141 Korean patients with schizophrenia, and 146 ethnically matched
      controls. DNA was amplified by a polymerase chain reaction-based method and
      digested by MaeIII, and the restriction fragment length polymorphism of two
      alleles, IL-10*C and IL-10*T, were assessed. There were no significant
      differences in genotype frequencies of IL-10*T/T, IL-10*T/C, and IL-10*C/C as
      well as allelic frequencies of IL-10*T and IL-10*C between patients with major
      depression and controls in the Korean population. Comparison of genotype and
      allelic frequencies of IL-10 gene between patients with schizophrenia and
      controls were also not significant. The present study suggests that IL-10 gene
      polymorphism at position -819 does not confer susceptibility to major depression
      and schizophrenia, at least in the Korean population. Further systematic studies
      including various clinical variables would be required.

PMID- 11952922
TI  - Beneficial effects of tandospirone on ataxia of a patient with Machado-Joseph
      disease.
AB  - Tandospirone citrate (tandospirone) is an anti-anxiety drug that acts by
      combining with serotonin receptor (5-hydroxytryptamine-1 A [5-HT1A]). Recently,
      there have been a few reports of its potential role in the treatment of
      cerebellar ataxia. We report the first case of a patient with Machado-Joseph
      disease in which we successfully treated cerebellar ataxia. In addition, his leg
      pain, insomnia, anorexia, and depression, which are thought to be related to 5
      HT1A receptors, were also remarkably alleviated by treatment with tandospirone.

PMID- 11952923
TI  - Effects of group musical therapy on inpatients with chronic psychoses: a
      controlled study.
AB  - The objective of the present study was to examine the efficacy of group musical
      therapy for inpatients with DSM-IV schizophrenia or schizoaffective psychosis.
      Thirty-four therapy group subjects in a ward for long-stay female patients
      received 15 group musical therapy sessions over 4 months, while 32 waiting group
      subjects from another ward with the same function were to wait for the sessions
      until the studied course was completed. The assessment included measures of
      psychotic symptoms, objective quality of life and subjective musical experiences.
      Comparison of the groups indicated that significant advantages in the therapy
      group subjects were detected in some measures concerning personal relations and a
      subjective sense of participation in a chorus activity. However, the follow-up
      evaluation suggested that the improvement might not be durable. These findings
      suggested that the musical therapy had some, but possibly only short-lived,
      effects on personal relations and musical experiences of chronic psychotic
      patients.

PMID- 11952924
TI  - Sleep-related violence and low serum cholesterol: a preliminary study.
AB  - To examine whether there is a relationship between serum cholesterol level and
      sleep-related violence, we evaluated 15 patients with violent behavior during
      sleep (VBS) and 15 normal control subjects. The patient and control groups were
      matched for sex, age, and weight. There were 13 women and two men in each group.
      The patients with VBS had lower serum total cholesterol, triglyceride, and low
      density lipoprotein levels than the healthy subjects. Low cholesterol may effect
      serotonergic neuronal activity and some types of 5-HT receptors, then may be
      related to violent behavior during sleep.

PMID- 11952925
TI  - Monozygotic twin cases of the agenesis of the corpus callosum with schizophrenic
      disorder.
AB  - We report the identical monozygotic twin cases of agenesis of the corpus callosum
      that demonstrated schizophrenic disorder. Patients were 26-year-old twin brothers
      and both cases were diagnosed as having schizophrenia using DSM-III-R diagnostic
      criteria. On magnetic resonance imagings both cases demonstrated the total
      agenesis of the corpus callosum and the anterior commissure was hypertrophic. We
      speculated that the developmental disturbance of the corpus callosum might be
      related to the cause of the psychiatric disorders in the present cases.

PMID- 11952926
TI  - A case of brief psychosis associated with an arachnoid cyst.
AB  - Little is known about the arachnoid cyst and there have been few reports of it
      accompanying psychiatric disturbances. A 57-year-old patient was admitted due to
      sudden headache, auditory hallucination, and delusion of persecution. An
      arachnoid cyst was found in the anteromedial aspect of middle cranial fossa on
      his magnetic resonance image. This was his first psychotic episode and he was
      also negative to other clinical evaluations including endocrine system. His
      psychotic symptoms were suspected to be induced by the arachnoid cyst and it was
      well controlled by low-dose risperidone administration. He left hospital free
      from psychotic symptoms on 14th hospital day.

PMID- 11952928
TI  - Mirtazapine may have the propensity for developing a restless legs syndrome? A
      case report.

PMID- 11952927
TI  - Treatment of features of Obsessive-Compulsive Personality Disorder using
      carbamazepine.

PMID- 11952930
TI  - Epidemiology and demographic aspects of treated end-stage renal disease in the
      elderly.
AB  - Over the last 10 years an increasing number of patients worldwide have started
      dialysis or had transplantation. Many are elderly with complex comorbid
      conditions. Registries across the world all show a rapid and dramatic increase in
      the number of older patients accepted for renal replacement therapy. In addition,
      the number of patients who grow old on dialysis is increasing, leading to a
      marked change in the demographics of the renal population. Changes over time and
      across registries are discussed with reference to patient characteristics,
      survival statistics, and the trends seen with transplantation in the elderly.

PMID- 11952932
TI  - Withholding and withdrawal of dialysis in the elderly.
AB  - The awareness that many patients eligible for dialysis may live lives in which
      the burdens of treatment outweigh the benefits has led the renal community to
      establish guidelines to assist the health care team in advising patients of the
      potential outcomes of living with or without dialysis. The guidelines published
      have been personal, consensual, and evidence based. They share in common the
      principles of shared decision making and informed consent. Only the patient or
      his surrogate should make the decision regarding initiation or cessation of
      dialysis.

PMID- 11952931
TI  - ESRD in the geriatric population: the crisis of managed care and the opportunity
      of disease management.
AB  - The geriatric population with end-stage renal disease (ESRD) is placed at risk
      with regards to the quality and extent of medical coverage because of the rapidly
      changing financial environment. Managed care organizations (MCOs) are generally
      for-profit companies that must focus on the bottom line. While the verbal
      commitment to quality care is voiced, the financial pressures on MCOs have led to
      a decrease in coverage of many services and outright denial for some necessary
      treatments. While denying services, the MCOs have also reduced payments to
      providers for services rendered. The coverage crisis is compounded by health
      maintenance organizations (HMOs) quitting Medicare because the reimbursement from
      the Health Care Financing Administration (HCFA) is less than their costs. Because
      of the above issues which can potentially impact on the quality of care delivered
      to the ESRD geriatric population, a new approach to disease management has
      created the opportunity to improve total patient care to a level not yet achieved
      in the United States. Disease management encompasses integrated care across all
      disciplines. Every component of care can be tracked by a dedicated information
      system. Improvement in outcomes has far exceeded the U.S. Renal Data System
      (USRDS) benchmark performance measurements with a disease management model
      approach. The key to success is the health service coordinator (HSC), a senior
      nurse with many years of ESRD experience. This individual coordinates care across
      all disciplines and expedites necessary referrals. With rapid attention to
      patient needs there has been a significant reduction in hospital admissions,
      hospital length of stay, and emergency room visits. Patient care will steadily
      improve as the disease management system matures as a consequence of
      understanding the patients total physical and psychosocial needs.

PMID- 11952933
TI  - Hemodialysis in the elderly: vascular access and initiation of renal replacement
      therapy.
AB  - Elderly persons with kidney failure are faced with many important considerations.
      Factors contributing to the choice of vascular access are often related to issues
      that also affect the timing of initiation of dialysis. This article provides
      guidance in determining when elderly patients are likely to develop an increased
      risk for complications of chronic kidney failure and comorbid conditions, and
      should therefore assist clinicians in selecting optimal vascular access and in
      deciding when to advise patients to begin dialysis.

PMID- 11952934
TI  - Chronic peritoneal dialysis in the elderly.
AB  - Available data indicate that peritoneal dialysis (PD) offers some advantages for
      the increasing number of elderly patients with ESRD, such as hemodynamic
      stability, steady-state metabolic control, good control of hypertension,
      independence from hospital visits, and avoidance of repeated vascular access.
      Early referral promotes the establishment of peritoneal access and minimizes the
      consequences of uremia and subsequent morbidity and frequent hospitalization.
      Elderly patients have similar modality-related complications such as peritonitis,
      catheter-related complications, exit-site and tunnel infection, and hernias as
      younger patients. Comorbid conditions, malnutrition, and psychosocial status
      influence the survival of elderly patients on PD. Elderly patients are compliant
      and highly motivated to cooperate in treatment. They are more tolerant of changes
      and losses and have a greater sense of well-being, less illness and modality
      related stress, and fewer mood disturbances. Despite comorbid conditions, that
      significantly impair self-performance of dialysis, PD can be performed
      successfully if they have family support or access to a network of medical and
      social support, that is, home nurses, rehabilitation services, and chronic care
      dialysis units, or nursing homes.

PMID- 11952935
TI  - Comparison and survival of hemodialysis and peritoneal dialysis in the elderly.
AB  - Comparisons of clinical outcomes in hemodialysis (HD) and peritoneal dialysis
      (PD) patients have been marked by inconsistent results depending on the
      population studied and the methods used. In order to address this limitation of
      previous U.S. studies and to more specifically evaluate the higher-risk elderly
      population, we undertook a study of Medicare patients > or =67 years of age and
      assessed the comorbidity before they entered end-stage renal disease (ESRD)
      treatment. We then evaluated their survival outcomes at 6 month intervals in the
      follow-up period. In order to adequately assess the comorbidity we employed the
      Charlson comorbidity index and applied it to the comorbidity of the ESRD
      population up to 2 years before ESRD to characterize conditions from the start of
      ESRD treatment. We also counted inpatient hospital days in the 2 years prior to
      initiation of ESRD therapy as a marker of severity of disease. These two
      determinants of comorbidity were used to adjust the analysis along with other
      demographic and laboratory data. In the diabetic population, HD patients are
      shown to have a decreased risk of death, with the decrease ranging from 8%
      [relative risk (RR) (HD:PD) 0.82, 95% confidence interval (CI) 0.75-0.90] at
      month 6 to 54% [RR (HD:PD) 0.46, 95% CI 0.30-0.70] at month 48. In the
      nondiabetic population, HD patients are shown to have a 17% [RR (HD:PD) 1.17, 95%
      CI 1.07-1.28] increased risk of death in the first 6 months, and a decreased risk
      of death from months 6 to 48, a decrease ranging from 17% to 34%. Relative risks
      were significantly different from 1.0 at all intervals. These overall findings
      suggest that in the elderly population in the United States treated with PD had
      outcomes that were significantly worse than their HD patient counterparts, even
      after adjusting basic patient demographics, the comorbidity index, severity of
      disease with hospital days, demographics, and glomerular filtration rate (GFR) at
      the time of start of dialysis.

PMID- 11952936
TI  - Dialysis in nursing homes.
AB  - The number of geriatric end-stage renal disease (ESRD) patients in the United
      States is increasing disproportionately to other age groups on dialysis. Thus
      there will be more dialysis patients that will require the assistance of nursing
      homes or extended care facilities. Nursing homes may be beneficial for the
      geriatric patient in terms of social and physical rehabilitation. Many of these
      facilities, however, may not take care of or may not have the capacity to
      adequately care for dialysis patients. Such patients have a higher rate of
      peritonitis when on peritoneal dialysis (PD) and have higher mortality rates on
      hemodialysis (HD) or PD compared to similar dialysis patients in the community.
      Cooperation and communication between the dialysis center and the nursing home,
      given the complex management issues involved in the care of these patients, are
      essential. One promising approach to the care of elderly dialysis patients is an
      integration of nursing home and dialysis unit. Although another approach could be
      to more fully utilize the services of adult day care centers, this has proven
      logistically difficult and has not been reported to be successful since it was
      first suggested more than a decade ago.

PMID- 11952937
TI  - Quality of life and rehabilitation of elderly dialysis patients.
AB  - Chronologic age per se does not measure the ability of an individual to benefit
      from dialysis. Elderly patients gain added lifetime on dialysis that is
      satisfying, and elderly patients as a group often show better psychosocial
      adjustment to dialysis than do younger patients. However, the limitations in
      physical functioning that characterize chronic dialysis patients increase with
      patient age. The clinical challenge is to identify factors that contribute to
      patients' compromised functioning and to arrange targeted supportive services. An
      integrated comprehensive program can address elderly dialysis patients' multiple
      care needs. Strategies that improve outcomes by reducing the risks of elderly
      persons for increased disability, assisting them to function in their usual
      environment whenever possible, can also have benefits.

PMID- 11952938
TI  - Nutrition in elderly dialysis patients.
AB  - The end-stage renal disease (ESRD) population is aging, and currently
      approximately 50% of patients treated with maintenance dialysis are more than 65
      years old. With advancing age comes challenges to maintaining the nutritional
      status of these patients. As patients get older, purchasing and preparing food
      may become more difficult. In addition, appetite may decrease, the occurrence of
      intercurrent illnesses may become more frequent, and nutrient requirements
      change. Mobility may decline, as well as cognitive function, and the combination
      of several of these factors may result in malnutrition. Since malnutrition has
      been demonstrated to impact survival in dialysis patients of all ages,
      appropriate attention to nutritional status and its management is essential for
      the elderly dialysis patient. This article reviews the issues associated with the
      maintenance of good nutrition in the elderly dialysis patient and describes the
      potential causes of malnutrition in these patients. It also reviews the nutrient
      requirements for older dialysis patients (which differ somewhat from those of
      younger patients), as well as the assessment of their nutritional status.
      Finally, recommendations for management of nutrition in the elderly dialysis
      patient are discussed.

PMID- 11952939
TI  - Special clinical problems in geriatric patients.
AB  - The elderly dialysis patient presents several challenges to the nephrologist.
      Concurrent illnesses may complicate management, disabilities may interfere with
      mobility, hearing, and vision, and depression and mental incompetence may be
      present. For these reasons the physician and health care team should adopt a
      broad treatment plan, using expert help if needed in managing the patient and
      involving family members, clergy, and friends. While lifestyle changes are
      inevitable for the elderly with initiation of dialysis, satisfactory outcomes are
      possible. In the event of overwhelming illness and the patient's perception of
      the futility of continuation of dialysis, cessation of dialysis must be
      approached in a humane, considerate, and compassionate manner.

PMID- 11952940
TI  - Cardiovascular abnormalities and hypertension in the elderly dialysis patient.
AB  - Elderly individuals comprise an ever-increasing proportion of patients on renal
      replacement therapy (RRT). As in younger patients, cardiovascular events are the
      major cause of death in the elderly on RRT, although the relative proportion
      succumbing to cardiovascular events is similar to that in young patients. An
      important observation is that the elderly are particularly likely to experience
      higher mortality if dialysis technique is suboptimal; they also experience
      particular benefit from successful renal transplantation. The latter observation
      has led to an "old for old" program in Europe.

PMID- 11952941
TI  - The dialytic management of acute renal failure in the elderly.
AB  - In this article the different dialysis strategies in the management of acute
      renal failure (ARF) in the elderly are discussed. Although peritoneal dialysis
      (PD) offers some theoretical advantages, there are several medical and technical
      reasons why it is currently less frequently used. The choice between intermittent
      hemodialysis (HD) and continuous renal replacement therapy (CRRT) is determined
      by a number of considerations, the most important ones being hemodynamic
      stability, the need for hyperalimentation and/or ultrafiltration, and the local
      experience with one or both techniques. Some recent studies with CRRT in elderly
      ARF patients describe favorable results. Slow extended daily dialysis (SLEDD)
      modalities may be particularly indicated in elderly, critically ill ARF patients
      because these techniques combine the advantages of both CRRT and HD. Finally, the
      importance of the biocompatibility of dialysis membranes is discussed. Although
      there are a number of theoretical arguments to use biocompatible membranes, this
      opinion is not always supported by the results of recent comparative studies. It
      is the opinion of the authors that all dialysis strategies should be mastered and
      utilized for appropriate indications in elderly ARF patients.

PMID- 11952943
TI  - Screening -- the Trojan horse in preventive medicine?

PMID- 11952944
TI  - Malaria prevention in highland Kenya: indoor residual house-spraying vs.
      insecticide-treated bednets.
AB  - This study compares the effectiveness and cost-effectiveness of indoor residual
      house-spraying (IRS) and insecticide-treated bednets (ITNs) against infection
      with Plasmodium falciparum as part of malaria control in the highlands of western
      Kenya. Homesteads operationally targeted for IRS and ITNs during a district-based
      emergency response undertaken by an international relief agency were selected at
      random for evaluation. Five hundred and ninety homesteads were selected (200 with
      no vector control, 200 with IRS and 190 with ITNs). In July 2000, residents in
      these homesteads were randomly sampled according to three age-groups: 6 months-4
      years, 5-15 years, and > 15 years for the presence of P. falciparum antigen (Pf
      HRP-2) using the rapid whole blood immunochromatographic test (ICT). The
      prevalence of P. falciparum infection amongst household members not protected by
      either IRS or ITN was 13%. Sleeping under a treated bednet reduced the risk of
      infection by 63% (58-68%) and sleeping in a room sprayed with insecticide reduced
      the risk by 75% (73-76%). The economic cost per infection case prevented by IRS
      was US$ 9 compared to US$ 29 for ITNs. This study suggests that IRS may be both
      more effective and cheaper than ITNs in communities subjected to low, seasonal
      risks of infection and as such should be considered as part of the control
      armamentarium for malaria prevention.

PMID- 11952945
TI  - Comparison of three antigen detection methods for diagnosis and therapeutic
      monitoring of malaria: a field study from southern Vietnam.
AB  - OBJECTIVES: To compare the sensitivity, specificity and post-treatment
      persistence of three commonly used rapid antigen detection methods. METHOD: We
      studied 252 Vietnamese patients aged from 4 to 60 years, 157 with falciparum and
      95 with vivax malaria and 160 healthy volunteers. An initial blood sample was
      taken for microscopy, and OptiMAL, immunochromatographic test (ICT) malaria
      P.f./P.v. and Paracheck-Pf tests. Patients with falciparum malaria were treated
      with an artesunate-based combination regimen and those with vivax malaria
      received chloroquine. Eighty-seven patients with falciparum malaria who were
      initially positive for one of the antigen tests and who remained blood smear
      negative underwent follow-up testing over 28 days. RESULTS: Paracheck-Pf was the
      most sensitive test for Plasmodium falciparum (95.8% vs. 82.6% for ICT malaria
      P.f./P.v. and 49.7% for OptiMAL). Specificities were all 100%. For vivax malaria,
      OptiMAL performed better than ICT malaria P.f./P.v. (sensitivities 73.7% and
      20.0%, respectively), with 100% specificity in both cases. All tests had low
      sensitivities (< or = 75.0%) at parasitaemias < 1000/microl regardless of malaria
      species. During follow-up, Paracheck-Pf remained positive in the greatest
      proportion of patients, especially at higher parasitaemias (> 10,000/microl).
      Residual OptiMAL positivity occurred only in a relatively small proportion of
      patients (< 10%) with parasitaemias > 10,000/microl during the first 2 weeks
      after treatment. CONCLUSIONS: Although microscopy remains the gold standard for
      malaria diagnosis, Paracheck-Pf may prove a useful adjunctive test in
      uncomplicated falciparum malaria in southern Vietnam. OptiMAL had the lowest
      sensitivity for P. falciparum but it might have a use in the diagnosis of vivax
      malaria and perhaps to monitor efficacy of treatment for falciparum malaria where
      microscopy is unavailable.

PMID- 11952946
TI  - Appropriate treatment of malaria? Use of antimalarial drugs for children's fevers
      in district medical units, drug shops and homes in eastern Uganda.
AB  - OBJECTIVE: To evaluate the quality of pharmaceutical care of malaria for children
      in eastern Uganda prescribed at government health units and drug shops, and
      administered by caretakers at home; and to assess its appropriateness in relation
      to national treatment guidelines, which recommend chloroquine over 3 days.
      METHODS: We followed 463 children under 5 years whose caretakers attended two
      drug shops and two government health units to seek treatment for fever. The
      children were examined and the caretakers interviewed on the day of enrollment in
      the study (day 0), and in their homes on days 3 and 7. Data was collected on drug
      use prior to attending the shop or health unit, the treatment provided at these
      study sites, and the administration of drugs at home over the following 3 days.
      RESULTS: Before attending the study sites, 72% of children had already been given
      some biomedical drugs, and 40% had received the recommended drug, chloroquine.
      Health workers prescribed chloroquine for 94% of the children, but only 34% of
      the recommended doses followed guidelines. Two-thirds of the children were
      prescribed an injection of chloroquine. By day 3, according to caretaker reports,
      about 38% of the children had received chloroquine in compliance with the
      instructions given by the health workers and drug shop attendants. Only 28% of
      the children had received chloroquine at the optimal dose of 20-30 mg/kg
      recommended by national policy. CONCLUSION: The methods were useful for examining
      adherence of both caretakers and health care providers to national guidelines and
      the extent to which caretakers were compliant with providers' prescriptions.
      Chloroquine and antipyretics were the drugs of choice for fever in these areas of
      rural eastern Uganda. But children did not receive the recommended dosage of
      chloroquine because of lack of compliance on the parts of providers as well as
      users of health care.

PMID- 11952947
TI  - Comparison of nasopharyngeal aspirate and nasal swab specimens for detection of
      respiratory syncytial virus in different settings in a developing country.
AB  - OBJECTIVE: To compare detection of respiratory syncytial virus (RSV) for
      diagnostic purposes using nasopharyngeal aspirate (NPA) and nasal swabs (NS) in
      different clinical settings in a community study in Guinea-Bissau. METHOD: During
      1996-98 paired specimens were obtained from 635 children under 5 years of age
      (median: 274 days; interquartile range: 144-453 days) with symptoms of lower
      respiratory infections (LRI). The specimens were analysed by an enzyme-linked
      immunosorbent assay for RSV antigen in Guinea-Bissau and re-analysed in Denmark
      using the same assay. The gold standard for RSV antigen detection was defined as
      any test being positive. RESULTS: RSV antigen was detected in 84 (13%) children,
      the prevalence being 19% (41/219) among infants aged < 6 months, 12% (22/184) in
      infants aged 6-11 months, and 9% (21/230) in older children. Sensitivity of
      antigen detection was higher in NPA (92% in analyses in Guinea-Bissau and 98% in
      Denmark) than in NS (63% in analyses in Guinea-Bissau, 71% in Denmark).
      Specificity of RSV antigen detection was equally high in NPA and NS (99-100%).
      Time since onset of symptoms was significantly shorter in RSV antigen positive
      than negative samples. Sensitivity did not depend on clinical setting or age of
      the child. CONCLUSION: Using NS samples was associated with a 27-31% reduction in
      sensitivity compared with NPA specimens. As NPAs are costly and considered a
      nuisance by the population, it might be cost-effective in larger epidemiological
      studies to lose 25-30% in sensitivity but be able to collect samples from a much
      larger population.

PMID- 11952948
TI  - Dengue virus infection rate in field populations of female Aedes aegypti and
      Aedes albopictus in Singapore.
AB  - We developed a single-step reverse transcription-polymerase chain reaction (RT
      PCR) followed by a semi-nested PCR using an upstream consensus primer and four
      type-specific primers within the non-structural protein gene (NS3) of dengue
      viruses to type dengue viruses in field populations of female Aedes mosquitoes.
      This yielded diagnostic fragments of 169, 362, 265 and 426 base pairs for dengue
      virus types 1, 2, 3 and 4, respectively. From 1997 to 2000, 54 (6.9%) of 781
      Aedes aegypti and 67 (2.9%) of 2256 Aedes albopictus screened were positive for
      dengue viruses, with a declining trend. The most common dengue virus type
      detected in the Aedes mosquitoes was dengue-1. Details on the change of one
      serotype to another in the mosquito population over three consecutive years are
      discussed.

PMID- 11952949
TI  - Incidence and risk factors of probable dengue virus infection among Dutch
      travellers to Asia.
AB  - We studied the incidence of dengue virus (DEN) infections in a cohort of Dutch
      short-term travellers to endemic areas in Asia during 1991-92. Sera were
      collected before and after travel. All post-travel sera were tested for DEN
      immunoglobulin M (IgM) [IgM capture (MAC)-enzyme-linked immunosorbent assay
      (ELISA)] and IgG (indirect ELISA). Probable DEN infection was defined as IgM
      seroconversion or a fourfold rise in IgG ratio in the absence of cross-reaction
      with antibody to Japanese encephalitis virus (JEV). Infections were considered
      clinically apparent in case of febrile illness (> 24 H) with headache, myalgia,
      arthralgia or rash. Probable DEN infection was found in 13 of 447 travellers
      (incidence rate 30/1000 person-months, 95% CI 17.4-51.6). One infection was
      considered secondary; no haemorrhagic fever occurred. The clinical-to-subclinical
      infection rate was 1 : 3.3. The risk of infection showed marked seasonal
      variation. DEN infections are frequent in travellers to endemic areas in Asia;
      most remain subclinical.

PMID- 11952950
TI  - High fascioliasis infection in children linked to a man-made irrigation zone in
      Peru.
AB  - We detected 10 protozoan and nine helminth species in surveys of 338 5-15 year
      old Quechua schoolchildren in three communities of the Asillo zone of the Puno
      region, located at a very high altitude of 3910 m in the Peruvian Altiplano. The
      area proved to be hyperendemic for human fascioliasis with a 24.3% overall mean
      prevalence of Fasciola hepatica, local prevalences ranging between 18.8 and
      31.3%, and infection intensities of up to 2496 eggs per gram of faeces (epg),
      with 196-350 epg (mean: 279 epg) and 96-152 epg (123 epg) as arithmetic and
      geometric means, respectively. Prevalences did not significantly vary between
      schools and in relation to sex. No statistical differences were found in
      intensities between schools, nor according to sex or age groups between and
      within schools, although the highest overall egg counts were detected in girls
      and in the youngest age group. Asillo zone is a man-made irrigation area built
      only recently to which both liver fluke and lymnaeid snails have quickly adapted.
      The region appears to be isolated from the Northern Bolivian Altiplano natural
      endemic area. Such man-made water resources in high altitude areas of Andean
      countries pose a high fascioliasis risk. Significant positive association of F.
      hepatica with protozooses following a one host life cycle, such as Giardia
      intestinalis, suggests that human infection mainly occurs through drinking water.
      This is supported by additional evidence such as the absence of typical aquatic
      vegetation in the drainage channels inhabited by lymnaeid snails, the absence of
      aquatic vegetables in the traditional nutrition habits of the Quechua
      inhabitants, and the lack of potable water systems inside dwellings, which
      requires inhabitants to obtain water from irrigation canals and drainage
      channels.

PMID- 11952951
TI  - Mortality patterns, 1993-98, in a rural area of Burkina Faso, West Africa, based
      on the Nouna demographic surveillance system.
AB  - The Nouna demographic surveillance system database was analysed for the period
      1993-98. Basic demographic parameters, age-specific and age-standardized
      mortality rates were calculated and a seasonal variation in mortality was
      analysed. Poisson regression was used to model the calculated mortality rates and
      to investigate the seasonal mortality pattern. Both the population distribution
      by age and the mortality rates reflect a typical pattern of population structures
      and total mortality in rural Africa as a whole: high childhood mortality and a
      young population (about 60% are up to age 25; about 10% above age 64). We
      identified a significant seasonal pattern with highest mortality rates in
      February. Demographic surveillance systems in Africa provide a viable method for
      the collection of reliable data on vital events in rural Africa and should
      therefore be established and supported.

PMID- 11952952
TI  - Molecular analysis of Cryptosporidium species isolated from HIV-infected patients
      in Thailand.
AB  - Cryptosporidium isolates from diarrhoeal stools of human immunodeficiency virus
      (HIV)-infected patients in Thailand were genetically analysed by sequencing the
      variable region in the 18S rRNA gene. Twenty-nine isolates from four children and
      25 adults attending King Chulalongkorn Memorial Hospital in Bangkok during 1996
      and 2000 were analysed. All patients suffered from chronic watery diarrhoea and
      had low CD4+ lymphocytes (mean +/- SD=105.5 +/- 133.2 cells/microl). Four
      Cryptosporidium species were identified, i.e. C. parvum (genotype 1), C.
      meleagridis, C. muris and C. felis occurring in 24, 3, 1 and 1 isolates,
      respectively. Oocysts of C. muris were significantly larger than oocysts of other
      species; C. felis was the smallest in these populations (P < 0.01). Sequences of
      the ITS1, 5.8S rRNA and ITS2 regions of C. muris and C. meleagridis identified in
      this study displayed unique sequences from those of other known species. Based on
      a limited number of isolates analysed, only C. meleagridis and C. muris were
      found in HIV-infected children, whereas the genotype 1 of C. parvum predominated
      in HIV-infected adults.

PMID- 11952953
TI  - Diagnosis of amoebic colitis by antigen capture ELISA in patients presenting with
      acute diarrhoea in Cairo, Egypt.
AB  - We studied 84 consecutive patients presenting with acute diarrhoea (less than 1
      week in duration) at an outpatient tropical medicine clinic in Cairo, Egypt. The
      diagnosis of amoebic colitis was established by the presence of Entamoeba
      histolytica galactose-inhibitable lectin antigen and the presence of occult blood
      in stool. Controls were 182 healthy regional people and 64 patients complaining
      of prolonged diarrhoea lasting more than 1 week. Entamoeba histolytica infection
      was found more frequently in patients with acute diarrhoea (57.1%) than in
      healthy controls (21.4%) or patients with prolonged diarrhoea (25%) (P < 0.001).
      There was a higher prevalence of Entamoeba dispar infection in the two control
      groups (24.2 and 20.3%, respectively, P=0.004 and 0.061) compared with those with
      acute diarrhoea (8.3%). Of the 84 patients with acute diarrhoea 32 had amoebic
      colitis (38%), and of these, 31 (97%) had at least one positive assay for serum
      amoebic antibodies (P < 0.001 compared with control groups). In summary, as
      determined by antigen-detection enzyme-linked immunosorbent assay, there is an
      unexpectedly high prevalence of amoebic colitis among patients presenting with
      acute diarrhoea to a tropical disease clinic in Cairo, Egypt.

PMID- 11952954
TI  - Chrysops silacea biting densities and transmission potential in an endemic area
      of human loiasis in south-west Cameroon.
AB  - We studied the biting densities of Chrysops silacea and the transmission of
      loiasis over 1 year in a regenerated forest in the south-west province of
      Cameroon. A total of 3015 flies caught near a wood fire at ground level during
      rainy and dry seasons were identified morphologically and 1975 caught during the
      rainy season were dissected to determine their physiological age and infection
      rate. The prevalence of microfilaraemia in the human population in the study area
      was determined using the thick blood smear method. Chrysops silacea was the only
      species caught. The daily and seasonal biting cycle of C. silacea showed two
      peaks of activities, 9-11 a.m. and 2-4 p.m. The biting cycles of parous and
      nulliparous flies showed the same trends, but the density of nulliparous flies
      biting at all time of the day was 2-3 times higher. Chrysops silacea biting
      density was high during the rainy season (9.06 +/- 6.88 flies/man/h) and lowest
      during the dry season (0.44 +/- 0.75 flies/man/h). An infection rate of 1.72% and
      a monthly morning and afternoon transmission potentials of 120769.11 and
      139016.64 infective head L3/man were observed, respectively, in the rainy season.
      Even though few Chrysops carried Loa loa infective larvae (0.7%), their parasite
      load was high, giving a high level of transmission of L. loa in the area. A total
      of 20.37% of the people examined for blood microfilariae were positive. These
      results suggest that the study area is an active focus of loiasis transmission.

PMID- 11952955
TI  - A controlled study of postpartum depression among Nepalese women: validation of
      the Edinburgh Postpartum Depression Scale in Kathmandu.
AB  - OBJECTIVES: To measure the prevalence of depression amongst postpartum and non
      postpartum Nepalese women in Kathmandu using the Edinburgh Postpartum Depression
      Scale (EPDS) and to assess the ease of use and validity of the scale compared
      with Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for
      major depression. METHODS: We screened 100 women 2-3 months post-delivery and 40
      control women using the EPDS. All those who screened positive for depression and
      20% of the negatives also underwent a structured interview to assess depression
      by DSM-IV criteria. RESULTS: Predictive errors were minimized by using an EPDS
      score > or =13 to define depression. Using this threshold, there was no
      difference in depression prevalence between postpartum women (12%) and the
      control group (12.5%) (Fisher's exact test, P > 0.05). Compared with DSM-IV, the
      sensitivity, specificity and positive predictive values were 100, 92.6 and 41.6%,
      respectively. CONCLUSIONS: The prevalence of postpartum depression (PPD) in
      Nepalese women and the validity and ease of use of the EPDS in the setting of a
      postnatal clinic in Kathmandu are all surprisingly similar to the results of
      numerous studies in developed countries. Despite poor living conditions, PPD is
      no more common than the background depression rate amongst Nepalese women. It can
      be reliably detected by trained clinical nurses using the EPDS screening test.
      These results may have implications for the planning of mental health resources
      for women in other developing countries.

PMID- 11952956
TI  - Supply-level measures to increase uptake of family planning services in Niger:
      the effectiveness of improving responsiveness.
AB  - OBJECTIVE: To show that low-cost attitudinal, structural and procedural changes
      aimed at improving responsiveness to patients have the potential to increase
      uptake of family planning (FP) even among populations considered reluctant to do
      so by health personnel. METHODS: Intervention study with before-after comparison
      of contraceptive acceptance, couple-years of protection (CYP) and an 'index of
      contraceptive uptake' (IUC) in rural health centres in Niger. The intervention
      consists of a package of instructions to actively propose family planning,
      integrated within curative and under-fives consultations, coupled with measures
      to increase the health centres' responsiveness to their clients. RESULTS:
      Implementation of the intervention package was followed by marked increases in
      family planning uptake. CONCLUSION: Health services in Niger present an untapped
      potential for improving family planning through low-cost supply-side measures.

PMID- 11952957
TI  - Growing complexity in the choice of Down's syndrome screening policy.

PMID- 11952958
TI  - Routine ultrasound for the prenatal diagnosis of congenital diaphragmatic hernia:
      the 'isms'.

PMID- 11952959
TI  - Congenital diaphragmatic hernia: evaluation of prenatal diagnosis in 20 European
      regions.
AB  - OBJECTIVE: To evaluate prenatal diagnosis of congenital diaphragmatic hernia by
      ultrasound in well-defined European populations. DESIGN: Data from 20 registries
      of congenital malformations in 12 European countries were included. The prenatal
      ultrasound screening programs in the countries ranged from no routine screening
      to three ultrasound investigations per patient being routinely performed.
      RESULTS: There were 187 cases with congenital diaphragmatic hernia, with an
      overall prenatal detection rate of 59% (110/187). There was considerable
      variation in prenatal detection rate between regions. There was a significant
      difference in the detection rate of isolated congenital diaphragmatic hernia
      (59/116, 51%) compared with congenital diaphragmatic hernia associated with
      multiple malformations, karyotype anomalies or syndromes (51/71, 72%) (P = 0.01).
      Termination of pregnancy was performed in 39 cases (21%) of which 14 cases were
      isolated congenital diaphragmatic hernia. Mean gestational age at discovery was
      24.2 weeks (range, 11-38 weeks). CONCLUSIONS: The overall prenatal detection rate
      of congenital diaphragmatic hernia is high (59%) but varies significantly between
      European regions. The gestational age at discovery was greater than 24 weeks in
      half of the prenatally diagnosed cases.

PMID- 11952960
TI  - Antenatal prediction of intraventricular hemorrhage in fetal growth restriction:
      what is the role of Doppler?
AB  - OBJECTIVE: To evaluate relationships between neonatal intraventricular hemorrhage
      and altered brain blood flow in preterm growth-restricted fetuses. METHODS: One
      hundred and thirteen growth-restricted fetuses (birth weight < 10th centile and
      umbilical artery pulsatility index > two standard deviations above gestational
      age mean) which delivered prematurely (< 34.0 weeks) were studied. Three
      expressions of altered brain blood flow were defined: 'brain sparing'= middle
      cerebral artery pulsatility index > two standard deviations below the gestational
      age mean, 'centralization' = ratio of middle cerebral artery/umbilical artery
      pulsatility indices (cerebroplacental ratio) > two standard deviations below the
      gestational age mean, and 'redistribution' = absent or reversed umbilical artery
      end-diastolic velocity. Intraventricular hemorrhage was graded after Papile (I
      IV) by cranial ultrasound performed within 7 days of delivery. RESULTS: Sixty
      seven (59.3%) fetuses had brain sparing, 84 (74.3%) had centralization and 51
      (45.1%) had redistribution. Fifteen (13.3%) neonates had intraventricular
      hemorrhage and were more likely to have a biophysical profile < 6, earlier
      delivery for fetal indications, lower cord artery pH, HCO3, hemoglobin, and
      platelets, a 10-min Apgar score < 7 and high perinatal mortality (5/15; 33.3%).
      No associations between intraventricular hemorrhage and brain sparing or
      centralization were identified. However, neonates with intraventricular
      hemorrhage had significantly higher umbilical artery pulsatility index deviations
      from the gestational age mean and a relative risk of 4.9-fold for
      intraventricular hemorrhage with redistribution (95% confidence interval, 1.5
      16.3; P < 0.005). Multiple logistic regression revealed significant associations
      between intraventricular hemorrhage and a low 10-min Apgar score (r = 0.30, P <
      0.005) and low hemoglobin (r = 0.28), gestational age at delivery (r = 0.25) and
      birth-weight centiles (r = 0.23) (P < 0.05). No Doppler parameter was identified
      as an independent contributor to intraventricular hemorrhage. CONCLUSION: While
      loss of umbilical artery end-diastolic velocity early in gestation significantly
      increases the risk for neonatal intraventricular hemorrhage, prematurity and
      difficult transition to extrauterine life remain the most important determinants
      of intraventricular hemorrhage.

PMID- 11952961
TI  - Cerebral hemodynamics and fetal behavioral states.
AB  - OBJECTIVE: This study aimed to evaluate the hemodynamic patterns of the proximal
      (M1) and distal (M2) portions of the middle cerebral artery, during different
      fetal behavioral states. DESIGN: The study included 20 normal singleton
      pregnancies at between 36 and 40 weeks of gestation. After identification of the
      fetal behavioral state (FBS), flow velocity evaluation was performed on the
      proximal and distal segments of the middle cerebral artery during 'quiescence'
      (FBS-1F) and 'activity' (FBS-2F). RESULTS: A statistically significant decrease
      of pulsatility index, reflecting a decrease of impedance to flow values, was
      identified in both segments of the middle cerebral artery (MCA) during
      'activity', with a more marked decrease in the MCA-M2 than in MCA-M1 (M1, P =
      0.0028; M2, P = 0.00000085). The mean fetal heart rate during 'quiescence' was
      significantly lower than during 'activity' (P = 0.0047). However, there was no
      significant correlation between the pulsatility index of both segments of the
      middle cerebral artery and the fetal heart rate during different fetal behavioral
      states. CONCLUSIONS: The results of this study provide evidence of the influence
      of different fetal behavioral states on fetal cerebral hemodynamic patterns. We
      believe it is better to sample the proximal segment in clinical practice because
      it is less influenced by fetal behavioral state. This information should be
      considered when evaluating fetal cerebral hemodynamics.

PMID- 11952962
TI  - Umbilical venous volume flow in the normally developing and growth-restricted
      human fetus.
AB  - OBJECTIVE: To determine the reproducibility of measurement of umbilical venous
      volume flow components and to calculate umbilical venous volume flow in normal
      and growth-restricted (small-for-gestational age) fetuses in a cross-sectional
      study. METHOD: Using Labview and Imaq-vision software, the cross-sectional inner
      area of the umbilical vein was traced. Vessel area (mm2) and Doppler-derived time
      averaged flow velocity (mm/s) were multiplied to calculate volume flow (mL/min)
      including flow per kg fetal weight. The coefficient of variation for vessel area
      and flow velocity scans and tracings were determined (n = 13; 26-35 weeks).
      Normal charts for components and volume flow were constructed (n = 100; 20-36
      weeks) and related to data from growth restricted fetuses (birth weight < 5th
      centile) (n = 33; 22-36 weeks). In growth-restricted fetuses the umbilical artery
      pulsatility index was also obtained. RESULTS: Reproducibility: The coefficient of
      variation was 5.4% (vessel area) and 7.3% (time-averaged velocity) for scans and
      6.6% and 10.5% for measurements, resulting in a coefficient of variation of 8.1%
      (scans) and 11.9% (measurements) for volume flow. A gestational age-related
      increase exists for vessel area, time-averaged flow velocity and umbilical venous
      volume flow from 33.2 (SD, 15.2) mL/min at 20 weeks to 221.0 (SD, 32.8) mL/min at
      36 weeks of gestation, but there is a reduction from 117.5 (SD, 33.6) mL/min to
      78.3 (SD, 12.4) mL/min for volume flow per kg fetal weight. In small-for
      gestational age fetuses, the values were below the normal range in 31 of 33 cases
      for volume flow and in 21 of 33 cases for volume flow per kg fetal weight.
      Umbilical artery pulsatility index was significantly different between the
      subsets with normal and those with reduced volume flow per kg fetal weight.
      CONCLUSIONS: Measurements of umbilical venous vessel area and time-averaged
      velocity resulted in acceptable reproducibility of volume flow calculations,
      which show a seven-fold increase at 20-36 weeks of gestation. In growth
      restricted fetuses, volume flow is significantly reduced. When calculated per
      kg/fetus, the values were reduced in 21 (63.6%) out of 33 cases.

PMID- 11952963
TI  - Chorionicity determination in twin pregnancies: how accurate are we?
AB  - OBJECTIVES: To determine the accuracy of antenatal prediction of chorionicity in
      twin pregnancies in our institution. METHODS: Antenatal chorionicity was
      determined using the number of placental masses, the presence or absence of a
      twin peak sign and the fetal sex. The gestational age at assessment was
      documented. Postnatal diagnosis of chorionicity was determined by neonatal sex
      and placental pathology. RESULTS: Chorionicity was correctly determined in 95% of
      cases (n = 131); 91% of the monochorionic and 96% of the dichorionic pregnancies
      were correctly determined. If chorionicity was assessed prior to 14 weeks'
      gestation (n = 96) the correct diagnosis was made in all except one case.
      CONCLUSIONS: Ultrasound assessment of chorionicity has a high sensitivity and
      specificity. This is further improved if the assessment is performed prior to 14
      weeks' gestation.

PMID- 11952964
TI  - First-trimester trisomy screening: nuchal translucency measurement training and
      quality assurance to correct and unify technique.
AB  - OBJECTIVE: To describe the process of training for measuring nuchal translucency
      at five clinical centers in North America and to evaluate methods of quality
      assurance and feedback. DESIGN: Throughout a period of 18 months, the performance
      of sonographers in measuring fetal nuchal translucency was monitored using
      qualitative and quantitative methods of review. After 12 months, different
      approaches (written and personal feedback) were used to inform sonographers of
      technical aspects that needed to or could be improved. RESULTS: On initial
      qualitative review, discrepancies in judgment from different reviewers coincided
      with suboptimal magnification, failure to visualize the amniotic membrane and/or
      use of cross-shaped calipers. At subsequent global review, 13 (29%) images of
      nuchal translucency measurements were considered unacceptable. Quantitative
      assessment revealed that, during the first part of the study, the means from four
      sonographers were significantly smaller and the mean from the fifth sonographer
      was significantly larger than expected on the basis of findings from The Fetal
      Medicine Foundation (P < 0.0001). Following feedback, sonographers who
      underestimated nuchal translucency and who received a written report only did not
      change measurements overall (P = 0.9759). In contrast, those who received
      additional intervention showed a marked difference (P < 0.0001). CONCLUSIONS:
      Global qualitative review of images from one sonographer may be preferable to
      assessment of individual aspects of images. Results from global qualitative
      review correspond well with findings from quantitative analysis, indicating that
      the latter can be applied for ongoing audit. Observation of divergent results
      should prompt extensive personal feedback, rather than a written report, to
      prevent sonographers from settling in their own, inappropriate technique.

PMID- 11952965
TI  - The sonographic approach to the detection of fetal cardiac anomalies in early
      pregnancy.
AB  - BACKGROUND: Transvaginal sonography enables imaging of the fetal heart in various
      planes and directions in early pregnancy. This study summarizes our experience in
      early detection of fetal cardiac anomalies. METHODS: Transvaginal sonographic
      examination was performed in 36 323 consecutive fetuses in both high- and low
      risk pregnancies. More than 99% of cases were evaluated at 14-16 weeks'
      gestation. Examination of the cardiovascular system did not rely on still images
      of the classic views but instead was performed in a dynamic mode visualizing the
      heart and great vessels from different directions and in various scanning planes.
      RESULTS: Cardiac anomalies were detected in 173 fetuses, giving an overall
      incidence of 1 in 210 pregnancies. In 44% of these, the cardiac anomaly was
      isolated. An abnormal karyotype was detected in 27 of the 72 cases that underwent
      chromosomal analysis. An abnormal nuchal translucency finding was observed in 59
      fetuses. The sonographic diagnosis was confirmed after delivery or at postmortem
      in 90 cases. Ten fetuses had a cardiac anomaly which differed from the anomaly
      suggested by sonography. In the remaining cases, a postmortem examination was not
      possible because termination of pregnancy was performed by dilatation and
      curettage. In four cases we did not detect the cardiac anomaly in early
      pregnancy. Two of them were detected at rescanning in mid-pregnancy. CONCLUSION:
      Early detection of fetal cardiac anomalies is now possible. Most anomalies occur
      in low-risk pregnancies. We suggest performing a detailed early multidirectional
      dynamic continuous sweep ultrasound examination of the fetal cardiovascular
      system in all pregnancies.

PMID- 11952966
TI  - Assessment of uterine artery blood flow in normal first-trimester pregnancies and
      in those complicated by uterine bleeding.
AB  - OBJECTIVE: To compare uterine artery blood flow in normal first-trimester
      pregnancies with those complicated by uterine bleeding. METHODS: Uterine artery
      blood flow was investigated by transvaginal color Doppler in 46 pregnant women
      affected by uterine bleeding and in a control group of 35 women with normal
      intrauterine pregnancy. Gestational age ranged from the 6th to the 12th week.
      Three blood flow values were calculated, the pulsatility index, the resistance
      index and the peak systolic velocity. Results were compared between the two
      groups. RESULTS: Of the 46 patients affected by uterine bleeding, 18 had an
      incomplete miscarriage, eight had a blighted ovum, five had a missed miscarriage
      and 15 continued their pregnancy until term and delivered liveborn infants. No
      significant differences were found in any of the three vascular indices between
      the normal and the pathological groups of patients. Uterine artery pulsatility
      and resistance indices decreased with gestational age in both normal and abnormal
      pregnancies but this change was not statistically significant. The peak systolic
      velocity significantly increased with gestational age in the control group but
      not in the pathological group. In patients with a retroplacental hematoma,
      uterine vascular resistance appeared higher than in those without a hematoma,
      while the peak systolic velocity showed no difference between the two groups.
      CONCLUSION: Doppler analysis of the uterine artery blood flow is unlikely to have
      a clinical role in the management of early pregnancies complicated by uterine
      bleeding.

PMID- 11952967
TI  - Accuracy in estimating fetal urinary bladder volume using a modified ultrasound
      technique.
AB  - OBJECTIVE: Fetal urine production at different gestational ages has been
      evaluated using ultrasound in several previous studies. In a recent study, we
      investigated the accuracy when estimating the bladder volume using the
      conventional ultrasound technique and found a total variability of 17.3-10.9% for
      bladder volumes of 5-40 mL. The variability is mainly caused by: (i)
      inappropriate image selection (the 'freezing error') and (ii) limitations when
      measuring on the frozen image (the 'frozen error'). The aim of this study was to
      reduce the total error by reducing the 'freezing' and the 'frozen error'. To this
      end, we used a modified manual ultrasound technique (adding a 'rocking' motion to
      the conventional method) and digitized the selected image. METHODS: Two patients
      for each gestational week from 24 to 40 weeks were selected. The fetal urinary
      bladder was examined with ultrasound three times within 1 min and documented on
      videotape. The volume, as assessed by the longitudinal section of the recorded
      bladder images, stored in digitized form, was evaluated on three occasions with >
      24 h in between. The mean and variability (standard deviation, SD) were
      estimated. RESULTS: For fetal bladder volumes between 5 and 40 mL, the 'freezing
      error' (SD), the 'frozen error' and the 'total error' were 11.7-5.1%, 8.0-3.0%
      and 14.2-5.9%, respectively. Comparing the present with a previous study, when
      selecting images and assessing bladder volumes repeatedly within 1 min, SD was
      12.9-5.5% vs. 17.3-10.9%. CONCLUSIONS: Using a modified ultrasound technique, the
      variability in fetal bladder volume estimation can be reduced.

PMID- 11952968
TI  - Strong impact of estrogen environment on Doppler variables used for
      differentiation between benign and malignant breast lesions.
AB  - OBJECTIVES: To analyze the impact of an estrogen environment on the Doppler
      variables usually used for differentiation between benign and malignant lesions.
      METHODS: A total of 142 malignant and 107 benign breast lesions was demonstrated
      (in 91 premenopausal and 152 postmenopausal patients) by B-mode ultrasound.
      Intratumoral vessels were visualized by color Doppler and blood flow velocity
      waveforms were analyzed by pulsed Doppler. The number of intratumoral vessels and
      the Doppler variables, peak systolic velocity, resistance and pulsatility indices
      and the peak systolic/diastolic ratio were evaluated in different endocrine
      milieus represented by menopausal status, phase of the menstrual cycle, intake of
      oral contraceptives or hormone replacement therapy. RESULTS: In malignant tumors
      the Doppler variables resistance and pulsatility indices and the
      systolic/diastolic ratio were significantly higher in postmenopausal women than
      in premenopausal women. In benign tumors significantly higher values of
      resistance and pulsatility indices were also detected in post- compared to
      premenopausal women (P < or = 0.05). In premenopausal patients with benign tumors
      taking oral contraceptives the number of intratumoral vessels was significantly
      higher, while resistance index and systolic/diastolic ratio values were decreased
      compared to patients with spontaneous menstrual cycles. In postmenopausal
      patients hormone replacement therapy did not influence Doppler variables in the
      benign or the malignant groups. CONCLUSION: Our results demonstrate a robust
      influence of menopausal status and oral contraceptives on Doppler variables of
      breast lesions. We believe it is likely that some of the differences in the
      Doppler variables found in reports comparing benign and malignant breast lesions
      were caused by their association with a pre- or postmenopausal status.

PMID- 11952970
TI  - Fetal pulmonary venous flow pattern is determined by left atrial pressure: report
      of two cases of left heart hypoplasia, one with patent and the other with closed
      interatrial communication.
AB  - We report two cases of fetal left heart hypoplasia with extremes of size of
      interatrial communication, i.e. a closed foramen ovale and an atrial septal
      defect. Doppler examinations of the pulmonary veins showed almost to and fro flow
      in the fetus with the closed foramen ovale and, in contrast, a normal flow
      velocity waveform in the fetus with the atrial septal defect, despite mitral
      atresia. Our observations support the importance of left atrial pressure in the
      creation of a pulmonary venous flow pattern in the fetus.

PMID- 11952969
TI  - Pelvic sonography and uterine artery color Doppler analysis in the diagnosis of
      female precocious puberty.
AB  - OBJECTIVES: To evaluate the role of ultrasound and color Doppler analyses in the
      diagnosis of precocious puberty. METHODS: Gray-scale sonographic uterine and
      ovarian evaluation together with color Doppler analysis of the uterine artery
      were prospectively performed in 29 girls presenting with premature breast
      development and pubic hair growth. The values were compared with results obtained
      from the gonodotrophin releasing hormone stimulation test. Excluded from the
      study were patients with isolated thelarche or isolated pubarche and those
      patients with gonodotrophin releasing hormone-independent puberty and with
      polycystic ovaries. RESULTS: According to the Tanner scale, all the girls
      presented a breast stage of 2-3 and pubic hair stage 2-3. The uterine size was
      greater in those girls who presented a pubertal response to the gonodotrophin
      releasing hormone test (Group II; n = 20) (8.07 +/- 4.47 mL) than in those who
      did not (Group I; n = 9) (3.07 +/- 1.18 mL; P = 0.001). The ovarian volume and
      the number of small follicles was not significantly different between the groups.
      On Doppler analysis, more elevated impedances were observed in Group I
      (pulsatility index = 3.28 +/- 0.37) than in Group II (pulsatility index = 2.29 +/
      0.19; P = 0.001) girls. The presence of a low pulsatility index (< 2.5) at the
      level of the uterine arteries had a high diagnostic value for precocious puberty
      (sensitivity 86%, specificity 100%). CONCLUSIONS: Uterine artery Doppler analysis
      may assist the diagnosis of gonodotrophin releasing hormone-dependent precocious
      puberty, may be useful for the selection of those girls needing treatment, and
      may simplify the follow-up of girls treated for precocities.

PMID- 11952971
TI  - Prenatal diagnosis of de novo mosaic deletion 13q associated with multiple
      abnormalities.
AB  - A case of prenatal diagnosis of de novo mosaic deletion of the long arm of
      chromosome 13 (del(13)(q13.3)) is presented. Routine scanning in a 27-year-old
      primigravida at 25 weeks' gestation showed fetal bilateral hydronephrosis.
      Detailed anomaly scanning in our tertiary referral center further demonstrated
      posterior meningoencephalocele, sloping forehead, microcephaly, syndactyly and
      hypoplastic thumbs. Both genetic amniocentesis and cordocentesis revealed a
      mosaic karyotype, 46,XY/46,XY,del(13)(q13.3). Sonographic findings were confirmed
      by postmortem autopsy and additional abnormalities such as agenesis of corpus
      callosum, hypoplastic cerebellum and macroglossia were diagnosed. Detailed
      sonography in this case thus revealed multiple malformations that prompted fetal
      karyotyping at 25 weeks' gestation.

PMID- 11952973
TI  - Fetal axillary hemangiolymphangioma with secondary intralesional bleeding: serial
      ultrasound findings.
AB  - A case of fetal axillary hemangiolymphangioma coexisting with intralesional
      hemorrhage is presented. At 27 weeks' gestation, the fetus was found to have a 52
      x 43-mm left axillary multilocular cystic mass which showed no signals on color
      Doppler. The mass was composed mostly of sonolucent spaces. At 29 weeks'
      gestation, an arterial flow signal (15 cm/s) was detected within the mass. In
      addition, two low-density echogenic cystic spaces with bidirectional flow
      waveforms were found, which raised the suspicion of intratumoral bleeding. Two
      weeks later, a fine-needle aspiration of the mass revealed both straw-colored and
      chocolate-colored fluid. The tumor size increased from 52 x 43 mm at 27 weeks to
      100 x 79 mm at 37 weeks. Blood clots developed gradually in the hemorrhagic
      spaces. The pregnancy proceeded smoothly to term and at 38 weeks an elective
      Cesarean section was performed. After a surgical excision of the mass at the age
      of 4 days, a mixed cavernous hemangioma and cystic lymphangioma with secondary
      intralesional hemorrhage was confirmed histopathologically.

PMID- 11952972
TI  - Initial experiences of tissue harmonic imaging in the diagnosis of fetal cardiac
      tumors.
AB  - The usefulness of tissue harmonic imaging in prenatal diagnosis is illustrated in
      two fetuses with a cardiac tumor. Tissue harmonic imaging provided more
      informative images than conventional B-mode imaging, enabling the detection of
      the site of attachment of the cardiac tumor and estimation of intracardiac blood
      flow. The advantages of tissue harmonic imaging over conventional B-mode imaging
      in prenatal diagnosis are discussed.

PMID- 11952974
TI  - Prenatal diagnosis of an infratentorial subdural hemorrhage: case report.
AB  - We report a case of a prenatally diagnosed infratentorial subdural hemorrhage.
      The hematoma located in the posterior cerebral fossa was detected by conventional
      ultrasound at 24 weeks of gestation. Intrauterine magnetic resonance imaging
      confirmed the diagnosis. Autopsy of the fetus revealed a well-circumscribed
      subdural hematoma. The prenatal findings of intracranial bleeding located in the
      posterior fossa and the prognosis of such cases are discussed.

PMID- 11952976
TI  - Prenatal three-dimensional sonographic images associated with Treacher Collins
      syndrome.

PMID- 11952975
TI  - Incidental ultrasound diagnosis of pseudomyxoma peritonei in an asymptomatic
      woman.
AB  - An incidental finding of pseudomyxoma peritonei is reported in a woman with a 6
      month history of postmenopausal bleeding. A transvaginal ultrasound scan revealed
      a poorly defined echogenic mass in the right iliac fossa above the right ovary
      and free fluid of mixed echogenicity in the pouch of Douglas. Laparoscopic
      appendicectomy and aspiration of mucinous fluid was performed without adjuvant
      chemotherapy. Regular postoperative follow-up scans, which are needed as the
      disease may have an indolent course, showed no signs of recurrence. The
      differential diagnosis and management of pseudomyxoma peritonei are discussed.

PMID- 11952977
TI  - Antenatal three-dimensional sonographic features of Treacher Collins syndrome.

PMID- 11952978
TI  - Transrectal sonography provides clearer anatomical delineation in a patient with
      partial vaginal agenesis and vesicovaginal fistula.

PMID- 11952979
TI  - Re: outcome of pregnancy in chromosomally normal fetuses with increased nuchal
      translucency in the first trimester.

PMID- 11952980
TI  - Prenatal sonographic diagnosis of median facial cleft should alert
      holoprosencephaly with premaxillary agenesis and prompt genetic investigations.

PMID- 11952981
TI  - First-trimester diagnosis of pleural effusion.

PMID- 11952983
TI  - Concentrates containing factor IX could improve haemostasis under conditions of
      thrombocytopenia: studies in an in vitro model.
AB  - BACKGROUND AND OBJECTIVES: We explored the effect on haemostasis of different
      factor IX (FIX) concentrates under thrombocytopenic conditions using an in vitro
      perfusion technique. MATERIALS AND METHODS: A moderate experimental
      thrombocytopenia (25 000-30 000 platelets/microl) was induced by means of a
      filtration procedure in blood anticoagulated with low-molecular-weight heparin.
      The effects of three different FIX concentrates - a prothrombin complex
      concentrate (PCC), an intermediate-purity concentrate (FIX/X), and a high-purity
      concentrate (HPFIX) - on platelet deposition and fibrin formation on
      subendothelium were assessed at two different shear rates (600/second and
      1200/second). Activation of the coagulation system was monitored through
      assessment of prothrombin activation fragment 1 + 2 (F1 + 2). RESULTS: Fibrin
      deposition increased after addition of FIX concentrates, but only showed a
      significant increase in experiments performed after incubation of PCC at the
      lower shear rate (600/second) (64.25 +/- 9.61% vs. control 31.22 +/- 8.02%; P <
      0.05). Addition of FIX concentrates caused a small increase in the percentage of
      platelet deposition and area of those aggregates. These differences reached
      levels of statistical significance in the presence of FIX/X and HPFIX in
      experiments performed at a shear rate of 600/second. F1 + 2 baseline values in
      anticoagulated thrombocytopenic blood were 1.15 +/- 0.13 nm and reached levels of
      2.49 +/- 0.24 and 3.60 +/- 0.33 nm at shear rates of 600 and 1200/second,
      respectively. Increments in F1 + 2 observed after addition of different FIX
      concentrates always remained in the previous ranges. CONCLUSIONS: Data from the
      present study provide experimental support favouring the concept that FIX
      concentrates containing other activated factors could improve haemostasis under
      conditions of moderate thrombocytopenia.

PMID- 11952984
TI  - Use of recombinant factor VIIa to treat persistent bleeding following dental
      extractions in two cirrhotic patients.
AB  - BACKGROUND AND OBJECTIVES: A single dose of recombinant factor VIIa (rFVIIa) has
      been shown to be effective and safe in correcting the prothrombin time (PT) in
      cirrhotic patients, but no clinical data exists demonstrating its efficacy in
      arresting active bleeding. MATERIALS AND METHODS: rFVIIa was used in two
      cirrhotic patients for persistent bleeding following dental extractions despite
      repeated treatment at the wound site and, in one case, repeated administrations
      of fresh-frozen plasma (FFP). RESULTS: Bleeding stopped promptly in both patients
      after administration of rFVIIa. However, bleeding recurred in the patient who had
      not received concomitant treatment at the extraction sites. No recurrence of
      bleeding was observed in the second patient, who underwent local treatment 15 min
      after rFVIIa. CONCLUSIONS: Recombinant factor VIIa arrested bleeding after dental
      extractions in two cirrhotic patients who had been unsuccessfully treated with
      FFP. However, additional local treatment is needed to limit the risk of
      recurrence as a result of the short half-life of rFVIIa.

PMID- 11952985
TI  - Increased non-transferrin bound iron in plasma-depleted SAG-M red blood cell
      units.
AB  - BACKGROUND AND OBJECTIVES: Non-transferrin bound iron (NTBI) is associated with
      increased morbidity in a number of transfusion-dependent disease states such as
      the severe haemoglobinopathies. We hypothesized that this may be related to
      excess NTBI present in plasma-depleted red blood cell units that are free of
      clear haemolysis. MATERIALS AND METHODS: The level of NTBI was determined using
      the bleomycin assay in samples from 20 stored plasma-depleted red cell units, at
      approximate 5-day intervals up to day 33 after donation. Forty units of fresh
      frozen plasma (FFP) and 40 units of platelet concentrates were used as negative
      controls, and samples from 12 units of FFP were also serially assessed. RESULTS:
      Median [interquartile range (IQR)] NTBI was 0 microm (0-0.35) in samples taken
      from units 3-10 days after donation. Thereafter, the levels of NTBI increased,
      becoming significant (median 3.05; IQR: 0.05-6.7 microm) 17-22 days after
      donation. After 30 days, NTBI was detectable in all red cell units. NTBI was
      undetectable in platelet concentrates and FFP. CONCLUSIONS: Increased levels of
      NTBI become detectable 17-22 days after donation and increase further with
      storage time. This excess NTBI may promote bacterial infection in iron-loaded
      individuals.

PMID- 11952986
TI  - Back-priming of the RCM1 leucocyte-reduction filter: consequences for filtration
      efficacy.
AB  - BACKGROUND AND OBJECTIVES: The RCM1 leucocyte-reduction filter has been
      incorporated into two types of blood-donation sets of which one uses back-priming
      of the leucocyte filter with SAG-M solution. In this study we have compared the
      leucocyte-reduction efficacy of the RCM1 filter with or without back priming with
      SAG-M solution. MATERIALS AND METHODS: This study was a retrospective analysis of
      quality control data of 3529 leucocyte-filtered red cell units. Of these, 1002
      whole-blood units were collected in a donation set that was back-primed by
      letting the SAG-M solution in the final storage bag run backwards through the
      filter into the bag of concentrated red cells. The remaining 2527 units were
      collected in a donation set that required no back-priming. Postfiltration
      leucocyte concentration was assessed using flow cytometry. RESULTS: There was a
      significant trend towards lower leucocyte concentration in the units in which
      back-priming of the filter preceded filtration, as compared to units filtered
      without back-priming [chi2trend= 18.8, degrees of freedom (d.f.) = 1, P <
      0.0005]. CONCLUSIONS: Back-priming of the RCM1 filter for red cells with SAG-M
      solution is superior to no back-priming with regard to leucocyte-reduction
      efficacy.

PMID- 11952987
TI  - Storage of platelets in additive solutions: a pilot in vitro study of the effects
      of potassium and magnesium.
AB  - BACKGROUND AND OBJECTIVES: Platelet additive solutions (PAS) have been shown to
      be suitable for extended platelet storage but have required the carryover of
      substantial (30%) amounts of plasma for success. Improving platelet quality by
      optimizing the composition of PAS may allow a reduction to be made in the amount
      of plasma carried over. Reducing the proportion of plasma carried over would
      facilitate some methods of viral inactivation and make available greater amounts
      of plasma for other needs. MATERIALS AND METHODS: Platelets from six pools of 25
      buffy coat platelet units and five apheresis platelet units were aliquoted for
      storage in plasma, or converted to PAS units in either a specific additive
      solution (PAS-III), with 30% or 20% plasma, or a modification of PAS-III
      containing 5.0 mm potassium and 1.5 mm magnesium (PAS-IIIM), with 30% or 20%
      plasma. Units were stored at room temperature with agitation for 7 days with in
      vitro testing for biochemical, haematological and functional parameters. RESULTS:
      Storage of platelets in PAS-IIIM resulted in a reduced rate of glycolysis and
      better retention of pH, morphology score and ATP levels. Platelets initially
      showed less evidence of activation when stored in PAS-IIIM, with reduced P
      selectin expression. Storage in PAS-IIIM with 20% (rather than the standard 30%)
      plasma appeared to result in the retention of in vitro properties, similarly to
      storage in standard PAS-III with 30% plasma. CONCLUSIONS: Storing platelets in an
      additive solution containing magnesium and potassium improves the functionality
      of the platelets, as measured by in vitro testing, and may allow a reduction of
      the amount of plasma required to be carried over to the final unit.

PMID- 11952988
TI  - DNA profiling: a valuable tool for quality control of sample logistics including
      occurrences of suspected sample confusion in a blood donation centre.
AB  - BACKGROUND AND OBJECTIVES: A molecular method for analysing whole-blood samples
      should be established for quality control of plasma sample logistics. MATERIALS
      AND METHODS: DNA profiles of retention samples (plasma) were compared to profiles
      of recent donations (whole blood). DNA extraction, amplification and detection
      were performed using the Qiagen DNA Blood Mini kit, the AmpFFISTR Profiler Plus
      Kit and capillary electrophoresis, respectively. RESULTS: Matched pairs of full
      profiles were obtained for all samples investigated, therefore no deviation from
      the standardized procedures was detected. CONCLUSIONS: Modified extraction and
      amplification protocols enabled DNA profiling to be used for the quality control
      of plasma samples. Hence, DNA profiling can be used in the blood bank as a safe
      and easy method for quality control of sample logistics.

PMID- 11952989
TI  - Allogeneic blood transfusion and postoperative duration of mechanical
      ventilation: effects of red cell supernatant, platelet supernatant, plasma
      components and total transfused fluid.
AB  - BACKGROUND AND OBJECTIVES: In patients undergoing open-heart surgery, allogeneic
      blood transfusion (ABT) may be related to an enhanced inflammatory response and
      impaired pulmonary function, resulting in a need for prolonged mechanical
      ventilation. Transfused red blood cell (RBC) supernatant, platelet supernatant or
      plasma components, may exercise varying effects on pulmonary function, because
      these fluids differ in their content of soluble biological-response modifiers.
      MATERIALS AND METHODS: The records of 416 patients undergoing coronary artery
      bypass graft operations at the Massachusetts General Hospital were reviewed.
      Possible predictors and the number of days of postoperative ventilation, as well
      as the number of all transfused blood components, were recorded. The association
      between mechanical ventilation past the day of operation and the volume of
      transfused RBC supernatant, platelet supernatant, or plasma components, was
      calculated by logistic regression analyses. RESULTS: The volume of each
      transfused fluid differed (P < 0.0001) among patients ventilated for 0, 1, 2, 3,
      or > or = 4 days after the day of the operation. After adjusting for the effects
      of confounding factors, the volume of administered RBC supernatant was associated
      (P = 0.0312) with the likelihood of postoperative ventilation past the day of
      operation, but the volume of platelet supernatant, plasma components, or total
      transfused fluid was not (P = 0.1528, P = 0.1847, and P = 0.0504, respectively).
      CONCLUSIONS: These results are congruent with the hypotheses that ABT may impair
      postoperative pulmonary function and that any such adverse effect of ABT is
      probably mediated by the supernatant fluid of stored RBCs. Both hypotheses should
      be examined further, in future studies of the outcomes of ABT.

PMID- 11952990
TI  - Supernatants of stored polymorphonuclear neutrophils exhibit growth-promoting
      activity in several cell lines: perforin expression in polymorphonuclear
      neutrophils and its role in down-regulation of growth-promoting activity.
AB  - BACKGROUND AND OBJECTIVES: Polymorphonuclear neutrophils (PMNs) play important
      roles in the host immune defence. This study was performed to identify roles of
      PMNs other than those already known. MATERIALS AND METHODS: PMNs were separated
      from the peripheral blood of healthy individuals and stored in vitro for 24 h in
      the presence or absence of an anti-human Fc receptor (FcR) gamma III antibody,
      namely, anti-CD16 monoclonal antibody (mAb). Stored supernatants were harvested
      and incubated with several leukaemia and transformed cell lines for 48 h. The
      increase in growth rate was assessed by the increase in the amount of 3H
      thymidine incorporated into these cells. Expression of perforin on PMNs, which is
      thought to decrease cell viability, was elucidated by flow cytometry (FCM)
      analysis. The presence of perforin in the stored supernatants was determined
      using an enzyme-linked immunosorbent assay (ELISA). A serine protease inhibitor,
      which is known to block the effect of perforin, was added to the cultures of
      several leukaemia and transformed cell lines to confirm the effect of perforin in
      reducing cell viability. RESULTS: Growth promotion of some cell lines cultured
      with the stored supernatants of PMNs was observed both in the presence and
      absence of anti-CD16 mAb, which was used as a trigger molecule of PMNs. This was
      particularly notable in the case of Raji and Daudi (both Burkitt lymphoma) cell
      lines and Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines (B
      LCLs) derived from healthy individuals. Perforin expression was observed in both
      freshly prepared and stored PMNs, regardless of the presence or absence of anti
      CD16 mAb. ELISA also detected perforin in the stored supernatants in both the
      presence and absence of anti-CD16 mAb. The increase in growth rate was induced in
      the presence of not only a serine protease inhibitor but also an anti-perforin
      mAb. CONCLUSIONS: Stored supernatants of PMNs exhibit up-regulation of cell
      growth in several cell lines; this up-regulation is particularly prominent in B
      lineage cell lines. Furthermore, perforin appeared to be expressed on PMNs
      constitutively and secreted into the extracellular fluid. Results of this study
      strongly suggest that the growth-promoting activity in supernatants of stored
      PMNs is partially inhibited by perforin, which is thought to be produced by PMNs
      themselves.

PMID- 11952991
TI  - Cytokine release in febrile non-haemolytic red cell transfusion reactions.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to elucidate the role and
      identity of cytokines involved in febrile non-haemolytic red cell transfusion
      reactions (FNHTRs). MATERIALS AND METHODS: Eighty-one patients experiencing
      transfusion reactions after receiving packed red blood cells (RBCs) were divided
      into three groups, as follows, based on the reaction experienced: FNHTRs (n =
      60); chills without fever (n = 8); and allergic reaction with urticaria (n = 13).
      The concentrations of interleukin (IL)-1beta, IL-6, IL-8 and tumour necrosis
      factor (TNF)-alpha were measured in the packed transfused unit and patients'
      plasma by using enzyme immunoassays. Wilcoxon's matched-pairs signed test was
      used to compare the difference in cytokine levels in patients' plasma before and
      after transfusion. The Kruskal-Wallis test was used first, followed by the Mann
      Whitney test, to compare the pretransfusion cytokine levels in patients' plasma
      between groups and to compare the cytokine levels in packed RBCs transfused to
      each group of patients. RESULTS: The age of the implicated packed RBC was 11.5 +/
      5.7 days. Significant increases were observed in IL-6 (P < 0.001) and IL-8 (P <
      0.001) patients' plasma levels, but not in IL-1beta or TNF-alpha levels, in those
      patients exhibiting FNHTR. No changes were observed in the patients' plasma
      samples of the other groups. Cytokine levels in the RBC concentrate supernatants
      were not appreciably elevated. CONCLUSIONS: Transfusion of packed RBCs may
      significantly increase intravascular levels of IL-6 and IL-8 in patients with
      FNHTRs.

PMID- 11952992
TI  - Antibodies to hepatitis B core in Danish blood donors: a surrogate marker for
      'high-risk' behaviour?

PMID- 11952994
TI  - TT virus infection in Brazilian Amazon Indians and comparison with non-Indian
      subjects.

PMID- 11952995
TI  - Quality controlling leucodepletion: a case of good practice or an illogical
      absurdity?

PMID- 11952997
TI  - The International Society of Blood Transfusion and A Code of Ethics for Blood
      Donation and Transfusion (2000).

PMID- 11953000
TI  - Self-awareness following traumatic brain injury and implications for
      rehabilitation.
AB  - PRIMARY OBJECTIVE: Many studies investigating self-awareness following traumatic
      brain injury (TBI) have been conducted more than 2 years post-injury, thereby
      providing limited information regarding the implications of insight for
      rehabilitation. The present study aimed to investigate awareness of deficits in a
      group of patients who were less than 2 years post-injury and still involved in
      rehabilitation. RESEARCH DESIGN: Thirty patients with a history of moderate or
      severe TBI and their significant other (SO) were studied in a cross-sectional
      analysis. A sub-group also participated in an interdisciplinary Memory Group at
      the Bethesda Rehabilitation Centre. METHODS AND PROCEDURES: Level of insight was
      measured by the degree of agreement between self and significant other (SO)
      report on the Awareness of Deficit questionnaire (ADQ), assessing various domains
      of daily functioning. RESULTS: There was substantial agreement between patients
      and their SO, although the patients with TBI were less likely to acknowledge
      executive problems. Interestingly, both groups reported only low-to-moderate
      levels of difficulty. CONCLUSIONS: The data indicate that SO's awareness may also
      be limited in the early recovery stages. A sub-group of the patients obtained
      benefit from participation in the Memory Group in a rehabilitation setting.

PMID- 11952999
TI  - Impact of UVA exposure on psychological parameters and circulating serotonin and
      melatonin.
AB  - BACKGROUND: People tend to feel better after exposure to ultraviolet (UV)
      radiation. This study was performed to investigate the impact of UVA exposure on
      psychological and neuroendocrine parameters. METHODS: Fifty-three volunteers were
      separated into 42 individuals who had UVA exposure and 11 individuals who had no
      UVA exposure. The UVA-exposed volunteers had irradiation sessions six times in a
      three-week period. All volunteers completed two questionnaires at baseline (T1)
      and at the end of the study (T3). For the determination of serotonin and
      melatonin serum levels of all volunteers blood samples were collected at baseline
      (T1), after the first UVA exposure (T2), and at the end of the study after the
      sixth exposure (T3). RESULTS: UVA-exposed volunteers felt significantly more
      balanced, less nervous, more strengthened, and more satisfied with their
      appearance at T3. By contrast, the controls did not show significant changes of
      psychological parameters. In comparison to T1 and T3, serum serotonin was
      significantly higher and the serum melatonin was significantly lower for the
      volunteers exposed to UVA at T2. Both, for exposed and non-exposed volunteers
      serotonin and melatonin levels did not significantly differ at T1 and T3.
      CONCLUSIONS: It remains obscure, whether the exposure to UVA or other components
      of the treatment were responsible for the psychological benefits observed. The
      changes of circulating neuroendocrine mediators found after UVA exposure at T2
      may be due to an UVA-induced effect via a cutaneous pathway. Nevertheless, the
      positive psychological effects observed in our study cannot be attributed to
      circulating serotonin or melatonin.

PMID- 11953001
TI  - The investigation of factors underlying deficits in self-awareness and self
      regulation.
AB  - PRIMARY OBJECTIVE: To examine a theoretical model which suggests that a
      contribution of both psychological and neuropsychological factors underlie
      deficits in self-awareness and self-regulation. RESEARCH DESIGN: Multivariate
      design including correlations and analysis of variance (ANOVA). METHODS: Sixty
      one subjects with acquired brain injury (ABI) were administered standardized
      measures of self-awareness and self-regulation. Psychological factors included
      measures of coping-related denial, personality-related denial and personality
      change. Neuropsychological factors included an estimate of IQ and two measures of
      executive functioning that assess capacity for volition and purposive behaviour.
      MAIN OUTCOMES AND RESULTS: The findings indicated that the relative contribution
      of neuropsychological factors to an outcome of deficits in self-awareness and
      self-regulation had a more direct effect than psychological factors. In general,
      measures of executive functioning had a direct relationship, while measures of
      coping-related and personality-related denial had an indirect relationship with
      measures of self-awareness and self-regulation. CONCLUSION: The findings
      highlighted the importance of measuring both neuropsychological and psychological
      factors and demonstrated that the relative contribution of these variables varies
      according to different levels of self-awareness and self-regulation.

PMID- 11953002
TI  - Family system outcome following acquired brain injury: clinical and research
      perspectives.
AB  - OBJECTIVES: To investigate family system outcome following acquired brain injury
      (ABI) using the Family Assessment Measure-III (FAM-III). RESEARCH DESIGN: Clients
      and families referred to the Family Support Service completed the FAM-III, a
      measure of family system functioning. METHODS AND PROCEDURES: Forty-three persons
      and 92 family members completed the FAM-III as part of intake. FAM-III scores
      were calculated and compared within the family, between subscales, and with
      established norms. RESULTS: FAM-III scores of the family member sample were
      significantly elevated compared to individuals with ABI and compared to the norm
      across all seven domains of family functioning. No significant relationship was
      found between family member relationship status or time post-injury and overall
      FAM-III scores. CONCLUSIONS: Family members identified distressed family
      functioning across all domains compared to survivors and compared to population
      norms. The FAM-III provides clinical utility in assessing family system
      functioning and shows promise as a family system outcome measure.

PMID- 11953003
TI  - Early seizures following non-penetrating traumatic brain injury in adults: risk
      factors and clinical significance.
AB  - BACKGROUND: In the literature dissenting data are obtained about risk factors for
      early post-traumatic seizures and their impact on outcome. This study was
      conducted to obtain more information about the clinical significance of early
      seizures and their possible impact on the treatment of traumatic brain injury.
      METHODS AND RESULTS: A consecutive series of 1868 adult patients with head injury
      were analysed retrospectively. Demographic data of the patients, characteristics
      of the injury, and findings on CT scan were recorded. Risk factors for early post
      traumatic seizures were identified using univariate statistics. A multivariate
      logistic regression was performed to look for interaction of different variables.
      The impact of early post-traumatic seizures on outcome was examined in an
      analogous way. Chronic alcohol abuse, subdural haematoma and brain contusion were
      identified as independent risk factors for early post-traumatic seizures. A
      significant association of early post-traumatic seizures with an unfavourable
      outcome was observed, but this effect was small compared to other variables.
      CONCLUSIONS: Early post-traumatic seizures appear to be an acute reaction of the
      brain to cortical damage with little independent impact on the management of head
      injury.

PMID- 11953004
TI  - A light and electron microscopic study of oedematous human cerebral cortex in two
      patients with post-traumatic seizures.
AB  - PRIMARY OBJECTIVE: Brain cortical biopsies of two patients with clinical
      diagnosis of complicated brain trauma who had seizures, were studied by means of
      light and electron microscopes in order to correlate structural alterations with
      seizure activity. METHODS AND PROCEDURES: Biopsy samples of left frontal cortex
      and right parietal cortex were processed by current techniques for light and
      transmission electron microscopy. RESULTS: The tissue showed severe vasogenic
      oedema with perivascular and intraparenchymatous haemorrhages. At the capillary
      wall, increased vesicular and vacuolar transendothelial transport, open
      endothelial junctions, thickened basement membrane and swollen perivascular
      astrocytic end-feet were observed. Some pyramidal and non-pyramidal nerve cells
      appeared dense and shrunken and others exhibited marked intraneuronal enlargement
      of membrane compartment. The myelinated axons displayed signs of degeneration and
      a process of axonal sprouting. Numerous swollen asymmetrical axo-dendritic
      synaptic contacts were observed in the neuropil, which exhibited mostly closely
      aggregated spheroidal synaptic vesicles toward the presynaptic membrane and
      numerous exocytotic vesicles sites. The perisynaptic astrocytic ensheathment
      appeared retracted or absent, whereas the extracellular space appeared notably
      dilated. Synaptic disassembly was also observed. CONCLUSION: The findings
      demonstrate, in two patients with post-traumatic seizure activity, brain barrier
      dysfunction, vasogenic oedema, anoxic-ischaemic neurons, axonal sprouting,
      numerous altered excitatory synapses and synaptic disassembly. Some
      considerations on clinical and research applications are discussed.

PMID- 11953005
TI  - The effects of brain injury on choice and sensitivity to remote consequences:
      deficits in discriminating response-consequence relations.
AB  - PRIMARY OBJECTIVE: One characteristic of some decision-making deficits is a
      failure to respond adaptively to consequences that follow choices. This
      investigation examined the sensitivity of choice to remote consequences with a
      high overall reinforcement rate and proximal consequences with a low overall
      reinforcement rate. METHODS: Three control and three subjects with brain injury
      made repeated choices between two reinforcement schedules: a fixed time schedule
      (FT) that delayed reinforcement by 12 seconds, and a progressive time schedule
      (PT) that progressively increased reinforcement delay by 2 seconds with each
      consecutive choice and reset to 0 seconds with each choice of the fixed schedule.
      Switching to the FT schedule at PT 6 seconds maximized overall reinforcement
      rate. RESULTS: Subjects with brain injury were less sensitive to contingencies
      and earned less reinforcement relative to controls because switching occurred at
      lengthy PT delays (delays far exceeding 6 seconds). CONCLUSIONS: Some deficits in
      decision-making and adaptation following injury may reflect a reduction in
      sensitivity to contingencies.

PMID- 11953006
TI  - Hypomania induced by herbal and pharmaceutical psychotropic medicines following
      mild traumatic brain injury.
AB  - The use of herbal medicines has become a very common practice. While many are
      safe enough to be available over-the-counter, they may pose risks due to
      interactions with pharmaceutical medications and effects in specific clinical
      populations. The case of a female patient with a history of mild traumatic brain
      injury and resulting depression is presented. She experienced hypomania after
      adding St John's wort and Ginkgo biloba to her regimen of fluoxetine and
      buspirone, which remitted after discontinuation of the herbal medicines.
      Implications for interactions between various psychopharmacologic agents,
      including herbal medicines and selective serotonin reuptake inhibitors (SSRIs),
      as well as the need for appropriate patient and health care provider education
      are discussed.

PMID- 11953007
TI  - Cloning of the chicken immunoglobulin joining (J)-chain gene and characterization
      of its promoter region.
AB  - Three overlapping genomic clones of the chicken immunoglobulin joining (J) chain
      were isolated and then characterized using restriction enzyme analysis, Southern
      blot analysis with cDNA probes, and DNA sequencing. The gene consisted of four
      exons separated by a 2.6-kb intron 1, a 0.9-kb intron 2, and a 0.5-kb intron 3. A
      transcriptional initiation site was identified by a primer extension method using
      mRNA and cDNA, indicating that exon 1 was 86 bp encoding 20 amino acid residues.
      A TATA box was positioned at 29 approximately 25 bp upstream of exon 1. Exons, 2,
      and 3 consisted of 133 bp and 81 bp, encoding 43 and 26 amino acid residues of
      the mature protein, respectively. Exon 4 consisted of 202 bp encoding 66 amino
      acid residues and 1.2 kb of untranslated sequence. Deletion mutants of a 4.1-kb
      genomic fragment containing exon 1 showed high levels of promoter activities when
      examined in luciferase reporter assays following transfection into the DT-40
      chicken B-cell line. These results suggest that the chicken J-chain gene consists
      of four exons and three introns and that the transcriptional regulatory elements
      may be present within 3.8 kb upstream of exon 1.

PMID- 11953008
TI  - Role of intracellular cationic liposome-DNA complex dissociation in transfection
      mediated by cationic lipids.
AB  - The cationic lipid-mediated gene transfer process involves sequential steps:
      internalization of the cationic lipid-DNA complexes inside the cells via an
      endocytosis-like mechanism, escape from endosomes, dissociation of the complex,
      and finally entry of free DNA into the nucleus. However, cationic lipid-DNA
      complex dissociation in the cytoplasm and the ability of the subsequently
      released DNA to enter the nucleus have not yet been demonstrated. In this report
      we showed, using confocal laser scanning analysis, that microinjection of a
      double fluorescent-labeled cationic lipid-pCMV-LacZ plasmid complex into the
      cytoplasm of HeLa cells results in efficient complex dissociation. However, the
      released DNA did not enter the nucleus, and no significant transfection could be
      detected. In contrast, nuclear microinjection of the cationic lipid-pCMV-LacZ
      plasmid complex resulted in efficient complex dissociation and transfection of
      all the cells. Taken together, the data suggest that intracellular dissociation
      of the cationic lipid-DNA complex is not a limiting step for transfection as
      previously thought.

PMID- 11953009
TI  - Comparison of responses elicited by immunization with a Legionella species common
      lipoprotein delivered as naked DNA or recombinant protein.
AB  - To evaluate the peptidoglycan-associated lipoprotein (PAL) antigen of Legionella
      pneumophila as a vaccine candidate, mice were immunized intramuscularly with
      pcDNA3-PAL and intraperitoneally with recombinant PAL (t-rPAL), which were
      compared for their ability to induce PAL-specific immune responses. The t-rPAL
      protein induced PAL-specific IgG antibody production significantly more than did
      pcDNA3-PAL. The IgG2a and IgG1 production was predominant after pcDNA3-PAL and t
      rPAL administration, respectively. In particular, pcDNA3-PAL induced much higher
      PAL-specific cytotoxic T-lymphocyte responses than did t-rPAL. Furthermore, in
      vivo, CD19+ B-cell populations were dramatically increased by t-rPAL vaccination,
      suggesting a B-cell immunomodulatory activity of the lipoprotein. The PAL antigen
      was also conserved among Legionella species, as determined by PCR and immunoblot
      analyses. These results support a potential use of the t-rPAL protein and in
      particular DNA vaccines against Legionella infections.

PMID- 11953010
TI  - Transfection of keratinocytes abrogates detectable DNA-binding activity of CCAAT
      displacement protein.
AB  - Transfection of keratinocytes with plasmid DNA leads to the loss of detectable
      DNA-binding activity of CCAAT displacement protein but not of Yin Yang 1, as
      monitored by electrophoretic mobility shift assay. This phenomenon was found to
      be attributable to the presence of plasmid DNA in the nuclear extracts prepared
      from transfected cells. Treatment of these nuclear extracts with DNase I restored
      the ability to monitor DNA-binding activity of CDP. This report documents a new
      pitfall associated with transfection.

PMID- 11953011
TI  - Molecular markers of endometrial epithelial cell mitogenesis mediated by the
      Sp/Kruppel-like factor BTEB1.
AB  - Basic transcription element binding (BTEB1) protein is one of at least 20 Sp/KLF
      family members that function as transcriptional activators or repressors by
      binding to GC/GT-rich sequences within target genes to influence cellular
      homeostasis in mammals. Previously, we demonstrated that increased expression of
      BTEB1 in a human endometrial epithelial cell line Hec-1-A resulted in serum
      dependent-enhanced proliferation, which was accompanied by heightened expression
      of cell cycle- and growth-associated genes. In the present study, we examined the
      mechanism underlying the altered proliferative potential associated with BTEB1 by
      the identification of additional BTEB1 downstream gene targets and by the
      demonstration of BTEB1 transactivation of promoters for a number of growth
      associated genes. Using mRNA differential display in the analysis of RNA
      populations from Hec-1-A sublines with high (4S, 9S) and low (2As, 3As) BTEB1
      cellular content, we identified 10 distinct differentially expressed transcripts,
      nine of which had higher levels in S than in As sublines. The expression levels
      of two of these cDNAs, Axl receptor tyrosine kinase and mitosin, whose encoded
      products are implicated in cellular proliferation, were modestly induced by
      serum, albeit in a BTEB1-independent manner. Moreover, insulin-like growth factor
      I, a mitogen present in serum, had no significant effect on their expression in
      either subline. In transient reporter assays, the basal activities of the Axl
      gene promoter and those for two other growth-regulatory genes, namely p21(WAF1)
      and IGFBP-2, were increased by serum and were significantly higher in 4S than in
      2As lines. However, while BTEB1 and its ubiquitous family member Sp1 increased
      basal p21(WAF1) and IGFBP-2 transcription when added as expression constructs in
      the parental Hec-1-A cell line, only Sp1 activated Axl transcription, despite the
      presence in all three gene promoters of GC-enriched regions that presumably can
      bind BTEB1 and Sp1 with similar affinities. To elucidate intracellular signaling
      pathways that might involve BTEB1, inhibitors of specific kinase-dependent
      transducers were used in transient transfection assays involving the IGFBP-2 gene
      promoter in 4S and 2As sublines. While inhibitors of the MAPK, PI-3K, and PKA
      pathways elicited similar effects on the IGFBP-2 gene promoter activity,
      irrespective of cellular BTEB1 content, that for JNK had a more pronounced effect
      on Hec-1-A sublines exhibiting higher BTEB1 expression levels. Taken together,
      the results suggest that BTEB1 mediates the expression of growth-associated genes
      through direct and indirect transactivation mechanisms, one of which may involve
      the participation of a JNK family member.

PMID- 11953012
TI  - Creation of superagonist epitope sequences in the hepatitis B envelope protein
      using mutagenesis and DNA vaccination.
AB  - DNA vaccination is a simple and efficient method for the induction of cytotoxic T
      lymphocytes (CTLs). In the present study, we have examined the effect of the
      mutations of each of the 12 amino acids of the HBsAg Ld-restricted CTL epitope on
      the ability of the modified proteins to induce CTLs after DNA-based immunization.
      Replacement of glutamine or serine by alanine codons in the whole envelope gene
      created a protein that induced higher CTL activity against cells bearing the
      wildtype peptide-MHC complex than against the wildtype sequence itself. These
      results represent the first example of immunogenic mutant sequences
      (superagonists) that induce higher CTL activity against the wildtype CTL epitope
      than does the wildtype protein. Because the entire mutant protein is being
      expressed from the modified plasmid, any of the various steps in epitope
      processing could be affected by the mutations and lead to increased class I
      immunogenicity of the peptide sequence.

PMID- 11953013
TI  - A great adventure in cell therapy.

PMID- 11953014
TI  - Adrian P. Gee, PhD, Editor Laureate.

PMID- 11953015
TI  - Elevated transforming growth factor beta levels in the plasma of cytokine-treated
      cancer patients and normal allogeneic stem cell donors.
AB  - BACKGROUND: Allogeneic blood stem-cell donors demonstrate more vigorous
      mobilization of CD34(+) cells to the circulation in response to cytokine
      administration than do autologous donors. Transforming growth factor (TGF-beta1)
      has been implicated as a mobilization inhibitor. A study was designed to
      determine whether plasma TGF-beta1 levels are elevated in cytokine-mobilized
      autologous cancer donors compared with cytokine-mobilized normal donors. METHODS:
      Plasma collected from 29 autologous cancer donors and 33 normal allogeneic stem
      cell donors following administration of mobilizing cytokines just prior to the
      first collection was assayed for TGF-beta1 using a sandwich-type ELISA. Plasma
      from three volunteers not treated with cytokine was also analyzed. Comparisons
      were made using the Student's t test on log-transformed data. RESULTS: Average
      TGF-beta1 levels in the plasma of cancer patients were significantly higher than
      in allogeneic stem-cell donors (4.4 ng/mL versus 7.2 ng/mL; p = 0.038). The
      allogeneic donors required fewer collections to harvest greater numbers of
      CD34(+) cells and colony-forming unit granulocyte-macrophage (CFU-GM) than
      autologous donors. Plasma from three untreated volunteers had mean TGF-beta1
      levels of 0.36 ng/mL, with all three levels below the 25th percentile for
      allogeneic donors and the 5th percentile for cancer patients. DISCUSSION:
      Cytokine administration was associated with increased plasma TGF-beta1 levels.
      The levels were higher in cancer patients being mobilized for stem-cell
      collection than in allogeneic blood stem-cell donors. These differences could
      underlie the increased number of apheresis procedures required to harvest
      autologous graft products from cancer patients.

PMID- 11953016
TI  - Comparison of monocyte enrichment by immuno-magnetic depletion or adherence for
      the clinical-scale generation of DC.
AB  - BACKGROUND: DC generated from monocytes have been used for vaccines. We have
      developed a monocyte enrichment procedure by depleting T and B cells with anti
      CD2 and anti-CD19 Abs using the automated Isolex 300i magnetic cell selector for
      clinical-scale DC generation in gas permeable SteriCell culture bags. We have
      also compared DC function, yield and purity of DC generated from adherent
      monocytes using culture bags in a closed system, with DC generated in
      conventional tissue culture flasks. METHODS: Monocytes were enriched from normal
      donor apheresis products using CD2/19 depletion with experimental software on the
      Isolex 300i (ISO), adherence (AD) to SteriCell bags and to T175 flasks and then
      cultured for 7 days in serum-free X-VIVO 15 media with GM-CSF and IL-4. Phenotype
      and dextran uptake were analyzed by flow cytometry and allogeneic MLR was also
      evaluated. RESULTS: ISO-DC and AD-DC from SteriCell bags showed similar
      viability. Higher purity of ISO-DC than AD-DC was measured by forward- and side
      scatter flow cytometry. Similar expression of CD1a, CD80, CD86 and CD83 were
      observed in both ISO-DC and AD-DC. Similar dextran uptake and allo MLR were also
      observed. DISCUSSION: These data indicated that functional DC were generated in
      gas permeable SteriCell culture bags from both ISO- and AD-monocytes in a closed
      system.

PMID- 11953017
TI  - Damage and protection of UC blood cells during cryopreservation.
AB  - BACKGROUND: Current procedures for the cryopreservation of umbilical cord blood
      (UCB) progenitor cells, which are based on techniques used for BM, have had
      varying degrees of success (survival 9-118%). Improving the effectiveness of UCB
      cell therapies demands a more comprehensive understanding of freezing injury
      during cryopreservation. METHODS: Leukocyte concentrates from UCB, with or
      without 10% DMSO were cooled at 1 degrees C/min to different subzero temperatures
      (-5 to -50 degrees C), then either thawed directly (thaw) or plunged into liquid
      nitrogen before thawing (plunge). Single-platform flow cytometry with 7-amino
      actinomycin D was used to directly quantify survival of CD34(+) cells.
      Fluorescent microscopy was used to examine plasma membrane integrity of nucleated
      cells. RESULTS: Without DMSO, recovery of nucleated cells was approximately 80%
      for both thaw and plunge. Survival was 9%, indicating damage to the plasma
      membrane. With 10% DMSO, nucleated cell recovery was also approximately 80%,
      indicating that DMSO does not improve recovery of nucleated cells. Survival,
      however, was much higher with DMSO, > 60% for nucleated cells thawed directly,
      and 30-55% for cells thawed from plunge, demonstrating cryoprotection conferred
      by DMSO. With DMSO, survival of CD34(+) cells was higher than that of nucleated
      cells, indicating that CD34(+) cells with 10% DMSO are more tolerant to
      cryopreservation than the total nucleated cell population. DISCUSSION: This study
      provides the necessary data on the low temperature response of UCB progenitor
      cells that are critical for the development of standards for the cryopreservation
      of UCB.

PMID- 11953019
TI  - Isolation and characterization of rapidly self-renewing stem cells from cultures
      of human marrow stromal cells.
AB  - BACKGROUND: The adult stem cells from BM, known as non-hematopoietic mesenchymal
      stem cells, or marrow stromal cells (MSCs), readily generate single-cell-derived
      colonies, but the cultures are known to contain cells with at least two different
      morphologies and different properties of differentiation. Recently, we tried to
      identify the earliest progenitors in the cultures. METHODS: Human MSCs were
      plated at very low initial densities of about 3 cells/cm(2), and the growth of
      colonies was followed by phase microscopy. RESULTS: The two kinds of
      morphologically distinct cells reported by others were readily discerned: large,
      slowly replicating cells and spindle-shaped, more rapidly replicating cells. In
      addition, we observed very small cells, with diameters of only about 7 microm,
      that very rapidly replicated, both symmetrically and asymmetrically. The small
      rapidly self-renewing (RS) cells had different surface epitopes and profiles of
      expressed proteins than other cells in the same cultures. They also had a greater
      capacity for multilineage differentiation. DISCUSSION: RS cells are apparently
      the earliest progenitors and most rapidly replicating cells in cultures of MSCs.
      They have properties that appear to make them ideal candidates for studying
      differentiation and probably make them well-suited for cell and gene therapy.

PMID- 11953020
TI  - Mesenchymal stem-cell therapy in a regulated environment.

PMID- 11953021
TI  - Marrow mesenchymal cell transplantation for genetic disorders of bone.

PMID- 11953022
TI  - Multilineage differentiation of human MSC after in utero transplantation.
AB  - Prenatal transplantation of stem cells is an exciting frontier for the treatment
      of many congenital diseases. The fetus may be an ideal recipient for stem cells,
      as it is immunologically immature and has rapidly proliferating cellular
      compartments that may support the engraftment of transplanted cells. Mesenchymal
      stem cells (MSC), given their ability to differentiate among multiple lineages,
      could potentially be used to treat diseases such as osteogenesis imperfecta,
      muscular dystrophy, and a variety of others that can be diagnosed in utero. We
      have shown, using a human-sheep in utero xenotransplantation model, that human
      MSC have the ability to engraft, differentiate into many tissue types, and
      survive for over 1 year in fetal lamb recipients. This observation warrants
      further studies of the behavior of MSC following systemic or site-directed
      transplantation.

PMID- 11953023
TI  - Prospective isolation of stromal progenitor cells from mouse BM.

PMID- 11953024
TI  - What is in a name? Defining the molecular phenotype of marrow stromal cells and
      their relationship to other stem/progenitor cells.

PMID- 11953025
TI  - Osteogenic stem-cell characterization and development: potentials for
      cytotherapy.
AB  - BACKGROUND: Primitive progenitors of bone tissue exist postnatally and exhibit
      stem-cell characteristics, as shown by extensive renewal potential, and capacity
      to differentiate into all characteristic connective tissue types, including bone,
      cartilage, fat, fibrous tissue, muscle and hemopoietic stroma. METHODS: A wide
      variety of investigative techniques have been applied to characterize and assess
      differentiation of the normally non-cycling osteogenic stem cells. These include
      methods to assess in vitro and in vivo differentiation potentials, the production
      and use of Abs to identify surface markers, the expression of specific genes and,
      more recently, incorporation of marker genes (beta-galactosidase, green
      fluorescent protein) to study cell fate after implantation at tissue sites.
      RESULTS: Some antigenic cell-surface molecules reactive with MAbs generated by a
      number of laboratories have been identified. For cell-fate studies, retroviral
      insertion of beta-galactosidase or green fluorescent protein genes into human
      marrow stromal progenitors has been accomplished with high efficiency. The
      stromal cell phenotype and cellular functions in vitro are not significantly
      altered by these genetic modifications. In vivo transplantation in
      immunodeficient animals demonstrates migration and persistence of marrow stromal
      cells to skeletal and other tissue sites. DISCUSSION: None of the Abs generated
      against surface markers of early progenitors are absolutely lineage and cell
      stage specific, but the respective Ags appear to participate in cell adhesion and
      cell-signalling mechanisms. These may be important in stem-cell activation and
      subsequent early osteogenic development. Studies of cell fate indicate
      feasibility for future uses in therapy of bone deficiency diseases and the
      potential for development of gene therapy procedures in these and other
      conditions.

PMID- 11953026
TI  - What do you want to be when you grow up?

PMID- 11953027
TI  - A simple and reliable procedure for cord blood banking, processing, and freezing:
      St Louis and Ohio Cord Blood Bank experiences.
AB  - BACKGROUND: In UC blood banking, volume and RBC reduction of the collected UC
      blood allows more efficient long-term storage and decreases infusion-related
      hemolysis and DMSO toxicity. However, high cell yields are imperative. At the St
      Louis Cord Blood Bank, we have systematically addressed processing/freezing and
      have developed a simple processing/freezing procedure. METHOD: The methodology is
      a modification of the hetastarch sedimentation and volume reduction approach of
      Rubinstein at the New York Placental Blood Program. Cord blood is mixed with a
      1:5 v/v ratio of hetastarch. The product is incubated for 45 min in an inverted
      position in a refrigerated centrifuge (4 degrees C), and then is spun for 5 min
      at 50 g. RBC concentrate is drained from the bottom. The volume drained is
      calculated to remove 80% of RBC. The UC blood unit is then resuspended and spun
      for 13 min at 420 g. Plasma is expressed from the top. RESULTS: A final product
      volume of 27 mL (range 16-58 mL) was obtained from an original 50-200 mL of UC
      blood collected. The average yield of total nucleated cells pre- and post
      processing was 90% for the first 4055 UC blood units banked. Pre- and post
      processing CFU and CD34 yields were tested in a cohort and were similarly
      conserved. With a processing time of 3 h for a single cord, this process is time
      efficient and lends itself well to processing several units at the same time. The
      technique has been exported to other laboratories with similar yields.
      DISCUSSION: This simple methodology results in reliable yields and is well suited
      to larger scale banking.

PMID- 11953029
TI  - CD133 (AC133) expression on AML cells and progenitors.
AB  - BACKGROUND: AML blasts differ in their functional capability, creating a
      hierarchy of progenitors. CD133 (AC133) is a newly described transmembrane
      protein expressed on CD34(+) and CD34(-) normal progenitors. We characterized the
      prognostic significance of CD133 expression in AML and expression of CD133 on AML
      progenitors thought to be responsible for maintaining this disease. METHODS: AML
      cells from 102 patients were analyzed for CD133 and CD34 expression, and
      correlated with outcome in 92 treated patients. AML cells were also FACS sorted
      into CD34(+)/CD133(+), CD34(+)/CD133(-), CD34(-)/CD133(+) and CD34(-)/CD133(-)
      subfractions, and assayed in vitro in colony-forming assay (CFU) and in
      suspension culture (SC) assay for up to 8 weeks, and in vivo in non-obese
      diabetic (NOD)/SCID mice to determine the phenotype of progenitors detected in
      these assays. RESULTS: CD133 expression was not correlated with event-free or
      overall survival, FAB subtype, cytogenetic abnormality or WBCC, but was
      correlated with CD34 expression. Primary AML CFU were present in all four sorted
      fractions. After an increasing period of time in SC, a higher proportion of cells
      capable of forming leukemic CFU were found in the CD34(+)/CD133(+) subfraction.
      Cells capable of producing leukemic engraftment in NOD/SCID mice were found in
      all subfractions, including the CD34(-)/CD133(-) subfraction in many patients.
      DISCUSSION: CD133 is not useful as a prognostic marker in AML. CD133 is expressed
      with CD34 on most primitive leukemic progenitors detected in vitro, however, in
      vivo progenitors could not be purified using CD133 in these patients.

PMID- 11953028
TI  - Low oxygen tension and autologous plasma enhance T-cell proliferation and CD49d
      expression density in serum-free media.
AB  - BACKGROUND: As cellular immunotherapy with ex vivo expanded cells becomes more
      widely used to treat a variety of illnesses, optimization of culture parameters,
      to maximize cell production and function, is essential for continued success. The
      effects of reduced oxygen tension and autologous plasma on T-cell expansion,
      receptor expression, apoptosis, and cytolytic activity in serum-free media were
      investigated. METHODS: PBMCs derived from whole blood samples were activated with
      anti-CD3 and anti-CD28 MAb in serum-free (AIM V) medium containing IL-2, and
      maintained at 5% and 20% oxygen tension. In some cases cultures were supplemented
      with 2% autologous plasma. RESULTS: Low oxygen enhanced T-cell expansion 13- and
      4.8-fold in serum-free and plasma-supplemented media, respectively. Autologous
      plasma also had a beneficial effect on T-cell cultures. Plasma-supplemented
      cultures expanded 74-fold more than serum-free cultures at low oxygen tension,
      and 43-fold more at high oxygen tension. Several samples expanded very poorly
      under serum-free conditions, and reasonable cell numbers were obtained only from
      plasma-supplemented cultures. CD49d expression density increased 3-fold to 4-fold
      in cultures supplemented with plasma. In contrast to our previous findings in
      serum-containing media, IL-2 receptor expression kinetics were unaffected by
      oxygen tension. No effects caused by oxygen tension or autologous plasma on
      expression of other surface antigens (CD4, CD8, CD44, CD95) were observed.
      DISCUSSION: Low oxygen tension and autologous plasma greatly increase expansion
      of T cells, thereby decreasing the time needed for production of cells for
      prophylaxis. Increased CD49d expression density may translate into improved
      migration and cytotoxicity.

PMID- 11953030
TI  - Decrease in circulating hematopoietic progenitor cells by trapping in the
      pulmonary circulation.
AB  - BACKGROUND: When stem-cell grafts are infused into the venous circulation and
      stem/progenitor cells egress from BM, pulmonary capillary beds are the first
      microcirculation site that they encounter. This provides the potential for
      circulating progenitor cells to be trapped in the pulmonary circulation. METHODS:
      We compared the number of progenitor cells [CD34(+) cells, colony-forming unit
      granulocyte-macrophage (CFU-GM), CD34(+) CD41(+) cells and CFU-megakaryocyte (CFU
      meg)] and their expression of cell-adhesion molecules (CAM) in samples taken
      simultaneously from radial arteries and central veins of 21 patients following
      PBSC mobilization. RESULTS: The mean (+/- SD) frequency of progenitor cells in
      the radial arteries was reduced to 79% +/- 25% for CD34(+) cells, 73% +/- 27% for
      CFU-GM, 77% +/- 25% for CD34(+) CD41(+) cells and 70% +/- 29% for CFU-meg of the
      number in the central veins. This suggests that some progenitor cells might be
      trapped in the lung. No association between progenitor-cell expression of CAM and
      pulmonary trapping was observed. DISCUSSION: Our data demonstrate pulmonary
      trapping of PBSC during mobilization, suggesting a potential inhibitory effect on
      PBSC harvest and medullary trafficking following graft infusion. However, the
      impact associated with pulmonary PBSC trapping may be negligible in the clinical
      setting if sufficient cells are infused.

PMID- 11953031
TI  - Complement-mediated T-cell depletion of bone marrow: comparison of T10B9.1A-31
      and Muromonab-Orthoclone OKT3.
AB  - BACKGROUND: T10B9.1A-31 (T(10)B(9)) and Muromonab-Orthoclone OKT3 (OKT3) are both
      murine MAb with a narrow specificity for T lymphocytes. Over the past 10 years,
      we have used each for T-cell depletion (TCD) of BM. In this report we describe
      similarities and differences using these antibodies, as well as their effects on
      patient outcome. METHODS: We compared BM mononuclear cells (BMMC) prepared using
      a Cobe Spectra apheresis machine with density gradient (DG) separation to remove
      RBC and enrich for CD34(+) cells prior to TCD. FACS and limiting dilution assays
      (LDA) were used to measure the efficiency of TCD, the subsets of cells removed
      and CD34 content. Univariate statistics were used to assess graft outcome,
      including GvHD, graft failure, post-transplant lymphoproliferative disease
      (PTLD), relapse, DFS, and TRM. RESULTS: BMMC preparation on the Cobe Spectra
      resulted in superior recovery of CD34(+) cells. However, this method could not be
      used with OKT3 due to inhibition of T-cell lysis. Optimal TCD required two rounds
      of complement at room temperature for OKT3, compared with one or two rounds for
      T(10)B(9). TCR(gamma delta)(+) T-cells, but not natural killer cells, were spared
      to a greater degree with T(10)B(9). Further T-cell loss occurred during culture
      with T(10)B(9) but not with OKT3. Overall efficiency of TCD was superior using
      T(10)B(9). The risk of acute GvHD was higher with OKT3-mediated TCD, independent
      of T-cell content, and may have led to a higher incidence of PTLD. A decreased
      risk of relapse for patients with high-risk disease was seen with OKT3-treated
      grafts, but engraftment, TRM and DFS did not significantly differ. DISCUSSION:
      TCD using OKT3 results in higher T-cell content and higher rates of acute GvHD
      and PTLD compared with T(10)B(9). Cobe Spectra cannot be used for BMMC processing
      with OKT3, fewer CD34(+) are therefore infused. Technical, as well as biological,
      differences between narrow specificity MAbs can affect graft outcome.

PMID- 11953032
TI  - CD34 selection using three immunoselection devices: comparison of T-cell depleted
      allografts.
AB  - BACKGROUND: T-cell depletion of allografts markedly reduces the incidence of GvHD
      following BMT. The approach taken at our Center has utilized the physical
      separation method of counterflow centrifugal elutriation (CCE), augmented by
      recovery of stem cells from lymphocyte-rich fractions by immunoaffinity selection
      of CD34(+) stem cells. We wanted to compare the performance characteristics of
      three commercially available selection devices, as well as the clinical outcomes
      of patients who received allografts engineered by the different devices. METHODS:
      BM allografts were prepared for patients undergoing BMT for hematologic
      malignancies. BM cells were separated into lymphocyte-rich and lymphocyte
      depleted fractions using CCE, followed by recovery of CD34(+) cells from the
      lymphocyte-rich fraction using one of three immunoselection devices [CellPro
      CEPRATE, Nexell Isolex 300i (software version 2.5) and AmCell CliniMACS].
      Allografts consisted of the lymphocyte-depleted fraction plus the CD34-selected
      fraction. RESULTS: Yields of CD34(+) cells were comparable for the three devices.
      However, there were significant differences in purity (CEPRATE < Isolex 300i <
      CliniMACS) and time from start of fractionation to infusion (CEPRATE < CliniMACS
      < Isolex 300i). More technical problems were encountered with the Isolex 300i
      device. Allograft compositions were comparable. Transplant outcomes (engraftment
      and incidence of GvHD) also were comparable. DISCUSSION: Qualitatively and
      quantitatively, allografts prepared with the CEPRATE, Isolex 300i (v 2.5) and
      CliniMACS devices should be considered comparable for use in this setting and
      probably also for direct T-cell depletion of BM.

PMID- 11953033
TI  - A negative-selection strategy for depleting myeloma cells from patients' BM
      and/or leukapheresis blood.
AB  - BACKGROUND: Autologous transplantation improves survival in multiple myeloma
      patients, however, most eventually relapse. As an attempt towards improving
      relapse-free survival, we designed a negative-selection purging strategy, to
      remove myeloma cells from leukapheresis harvests using MAbs specific for Ags on
      myeloma cells. METHODS: CD38 is highly expressed on myeloma plasma cells, but
      expressed at lower levels on normal progenitors and absent on in vivo
      repopulating cells. We evaluated depletion of CD38-expressing cells, with or
      without depletion of B-cell Ag-expressing cells. Using myeloma BM or blood cells
      diluted into allogeneic G-CSF primed leukapheresis cells, bispecific tetrameric
      Ab complexes that bind dextran iron particles were used to label and retain cells
      in a magnetic column, StemSep. Depletion efficacy was measured by semi
      quantitative allele-specific oligonucleotide (ASO)-PCR amplification of patients'
      clonotypic IgH gene. RESULTS: Low (0.2 microg/mL) concentrations of anti-CD38
      with CD19 and CD20 complexes depleted approximately 3-5 logs of clonotypic cells,
      with recovery of approximately 19% of colony-forming cells, approximately 50%
      primitive progenitors measured by LTCIC and retention of non-obese diabetic /SCID
      engrafting ability. Scale-up experiments using leukapheresis harvests and 0.5-1 x
      10(10) cell capacity columns demonstrated no loss of log depletion of highly
      positive cells, or recovery of unlabelled cells. DISCUSSION: These results
      compare favorably with other purging techniques and allow the retention of most
      normal BM cells, including T cells, which may be important for immunity. These
      results support the development of a clinical trial using this strategy for
      purging myeloma cells.

PMID- 11953035
TI  - Adoptive T-cell therapy for CMV.

PMID- 11953036
TI  - Adoptive transfer of Ag-specific T cells to prevent CMV disease after allogeneic
      stem-cell transplantation.
AB  - BACKGROUND: Cytomegalovirus is a major cause of infectious morbidity and
      mortality after allogeneic stem-cell transplantation (allo-SCT). Farmacotherapy
      to prevent or treat CMV reaction and infection is only partially effective, and
      has considerable toxicity. Adoptive transfer of ex vivo generated CMV specific T
      cells is a new approach to the management of CMV post-allo-SCT. METHODS: A
      comprehensive review of the published literature describing 1) the recovery of
      CMV immunity post-allo-SCT and 2) new strategies for the production of CMV
      specific T cells for adoptive immunotherapy. RESULTS: CMV specific T cells can be
      generated using a variety of systems comprising different antigen presenting
      cells and antigens. DISCUSSION: The ability to raise CMV specific T cells on a
      clinical scale will have a major impact on the management of CMV post-allo-SCT,
      but will have to be compared to current pharmacological approaches. Further, the
      raising of CMV specific T cells may serve as a model, to generate other antigen
      specific T cells including other anti-viral and anti-tumor T cells.

PMID- 11953038
TI  - Clinical trials with CMV-specific T cells.
AB  - BACKGROUND: Reactivation of latent CMV following allogeneic hematopoietic stem
      cell transplantation remains a major cause of morbidity despite improvements in
      surveillance protocols and antiviral drug therapies. Selective restoration of
      anti-CMV cellular immunity is an attractive alternative approach if it can be
      achieved in a non-toxic manner that can be widely utilized. The application of
      CMV-specific adoptive cellular therapies following the initial proof of principle
      provided almost a decade ago has been limited be a number of factors including
      the practical difficulties of exporting technically demanding and labor-intensive
      methodology to smaller transplant centers. METHODS: We review the lessons learnt
      from studies in the setting of EBV-associated post transplant lymphoproliferative
      disease and the advances in both understanding and technology that have allowed
      the development of a multitude of new approaches for the generation of CMV
      specific T cells suitable for adoptive transfer. These include the use of
      monoclytes, dendritic cells and B-lymphoblastoid cell lines as the presenting
      cells of antigen delivered by pulsing with exogenous proteins or peptides, or of
      antigen processed endogenously following transduction with one of a variety of
      viral vectors. We also discuss some of the issues surrounding the planning and
      implementation of trial protocols incorporating these products, and the
      techniques necessary for monitoring the fate of the infused cells and their
      efficacy. Finally, we review the preliminary data that is available on the newer
      generation of clinical trials that are ongoing in this field. DISCUSSION:
      Extensive characterization of many different systems used to culture CMV-specific
      cells has now been performed. These suggest that it is now possible to generate T
      cells with specificity for a number of different CMV-specific target antigens
      (most commonly the lower matrix protein pp65). Clinical trials using these
      products within the current regulatory guidelines ares till in their infancy.
      However, preliminary results are beginning to suggest that the newer generation
      of CMV-specific T cell products can be administered with a relatively low risk of
      graft-versus-host disease, and that antiviral activity can be demonstrated
      following infusion.

PMID- 11953037
TI  - IE1-pp65 recombinant protein from human CMV combined with a nanoparticulate
      carrier, SMBV, as a potential source for the development of anti-human CMV
      adoptive immunotherapy.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) infection and reactivation following
      allogeneic bone marrow transplantation is a major source of complications in
      grafted patients including pneumonitis, graft rejection and even death. Adoptive
      immunotherapy consisting in transfer of CD4(+) and CD8(+) T cells directed
      against HCMV has proved its worth. Nevertheless, established procedures have to
      be improved in terms of safety and waiting period required to obtain specific T
      cells. METHODS: As an alternative to infectious virus used in current strategies,
      we purified a recombinant protein IE1-pp65 resulting from the fusion of the
      regulatory IE1 and matrix pp65 proteins, both known as the major targets of the
      overall anti-HCMV T cell response. Based on our previous data demonstrating its
      use for in vitro stimulation and expansion of anti-HCMV CD4(+) and CD8(+) T cells
      (Vaz-Santiago et al, 2001, J.Virol, 75:7840-47) from peripheral blood mononuclear
      cells (PBMC) of seropositive donors, we planned to improve its in vitro
      immunogenicity through association with a nanoparticulate carrier, SMBV. RESULTS:
      We demonstrated that using of SMBV/IE1-pp65 formulation allowed to potentiate in
      vitro activation of T cells and to expand more CD8(+) T cells than with soluble
      IE1-pp65, following stimulation of PBMC. DISCUSSION: These data suggest the use
      of SMBV/IE1-pp65 formulation as a potential source of antigen for efficient T
      cells expansion in the development of safe anti-HCMV immunotherapy.

PMID- 11953039
TI  - Flow cytometric quantitation and characterization of the T-lymphocyte memory
      response to CMV in healthy donors.
AB  - BACKGROUND: Levels of circulating CMV Ag-specific lymphocytes determine CMV
      reactivation risk in immunocompromised individuals. METHODS: Frequencies of T
      cells producing cytokines after stimulation by CMV Ag were measured in
      hematopoietic stem-cell donors using flow cytometry. RESULTS: In seropositive
      individuals (n = 75) the mean number of CD8(+) (CD8(bright), CD8(dim)) and CD4(+)
      cells producing IFN-gamma was respectively 3.1% (12.6/microL) and 0.38%
      (3.2/microL), over 10-fold higher than in seronegative subjects (n = 22). CMV
      stimulation induced tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma
      (IFN-gamma) in both CD4(+) and CD8(+) cells (usually together), with a shift from
      memory- to effector-cell phenotype, while only a small proportion of CD4(+) cells
      produced IL-4. Although the normal range was wide, neither age, sex nor HLA type
      affected the frequency. DISCUSSION: These quantitative studies and the
      recognition of CD4(+) cells as potential effectors of CMV immunity are of
      relevance for immunotherapeutic approaches to prevent CMV disease after stem-cell
      transplantation.

PMID- 11953040
TI  - HLA tetramers and anti-CMV immune responses: from epitope to immunotherapy.
AB  - BACKGROUND: Identification of HLA class I-restricted CMV epitopes, and the
      subsequent synthesis of HLA class I-peptide tetrameric complexes, have provided
      investigators with an important tool for visualising and quantifying the precise
      in vivo CTL response to CMV reactivation following stem cell transplantation. In
      conjunction with PCR-monitoring of the viral load, the magnitude and dynamic of
      the host's specific CD8(+) T cell response to viral replication can be studied.
      METHODS: CMV peptide epitopes can be identified be searching the CMV-pp65 antigen
      for HLA class I allele binding motifs, by testing their binding affinity and
      ability to generate CTLs, and by screening for CTL responses in as many
      individuals as possible to assess their general applicability for monitoring
      large number of patients. HLA tetramers are synthesized by refolding recombinant
      class I heavy chains and beta(2)m with CMV-pp65(495-503) peptide. After
      biotinylation and tetramerisation to PE-conjugated streptavidin, they are used to
      stain CD8(+) T cells taken from patients at different time points after SCT.
      RESULTS: The T-cell mediated immune response is mainly directed against epitopes
      derived from the CMV tegument protein pp65. CMV-specific CTL's confer protection
      against CMV reactivation above a threshold level of 10(7) to 2 x 10(7)/L. CMV
      reactivation is required to stimulate CTL responses. Transfer of CMV immunity
      from seropositive donors is associated with better outcome and steroids suppress
      the Ag-specific immune response. DISCUSSION: Initial studies with CMV-specific
      HLA class I tetramers have helped to define the nature of anti-CMV T cell
      response in SCT patients and to determine a threshold CTL level required for
      controlling CMV reactivation. Monitoring patients with HLA-tetramers should
      therefore allow clinicians to predict and assess the risk of reactivation and to
      balance the risks and benefits of early anti-viral treatment, thereby avoiding
      the hazards of anti-viral prophylaxis. HLA-tetramers can also be used to isolate
      antigen-specific cells for further in vitro expansion and transfer to patients
      for antiviral immunotherapy. The threshold level determined from patient
      monitoring can be used as a guide for estimating an effective target cell dose.

PMID- 11953041
TI  - Induction of CMV-specific T-cell lines using Ag-presenting cells pulsed with CMV
      protein or peptide.
AB  - BACKGROUND: CMV disease is still associated with a high morbidity and mortality
      in recipients of a solid organ or stem cell graft, especially in patients
      undergoing allogenic stem cell transplantation. Reconstitution of CMV-specific
      CD4(+) and CD8(+) cytotoxic T cell responses are essential to control CMV
      infection following allogenic stem cell transplantation. The transfer of
      unselected populations of lymphocytes from the peripheral blood of a CMV
      scropositive donor to a transplant recipient can be used to control CMV
      infection. However, such transfer of unselected donor lymphocytes is limited by
      potentially fatal complications that arise from alloreactive T cells, also
      present in the unselected donor lymphocytes. Thus to make infusion of donor T
      cells safe and also more effective in controlling CMV infection in the recipient
      of the T cell infusion, T cells are manipulated in vitro to deplete alloreactive
      T cells and to enrich for CMV-specific T cells. METHODS: Using various antigen
      presenting cells (monocytes/PBMNCs/dendritic cells) and different modes of
      antigen presentation (infected APCs, pulsing of protein or peptide antigen)
      different CMV-specific T cell populations can be generated and expanded. RESULTS:
      Using protein-/or peptide-pulsed DCs CMV-specific CD8(+) cytoxic T cell lines
      (can be generated and expanded) in addition CMV-specific CD4(+) T cell lines can
      be generated when CMV-protein-pulsed DCs are used as antigen-presenting cells.
      When peripheral blood mononuclear cells were stimulated with CMV lysates
      predominantly CMV-specific CD4(+) T cells are generated and expanded ex vivo.
      DISCUSSION: Depending on the APC used (monocytes versus DC) and the mode of
      antigen presentation (protein versus peptide pulsing) different CMV-specific T
      cell populations of varying purity can be generated which show preserved function
      when tested for specific proliferation, cytokine production and cytotoxicity.

PMID- 11953042
TI  - Assessment of G-CSF stimulated BM hematopoietic stem cells in normal donors.
AB  - BACKGROUND: The clinical use of G-CSF has recently been expanded to include
      mobilization of stem cells for both autologous and allogeneic transplantation.
      Most of the published studies have focused on stem cells released into the
      peripheral blood (PB) after G-CSF treatment. However, little is known about the
      effects of G-CSF on BM. This study evaluated the concurrent effects of short-term
      G-CSF on both BM and PB stem and progenitor cells in normal individuals. METHODS:
      Volunteers received 5 or 10 microg/kg of G-CSF for 5 consecutive days (Days 1-5).
      On Days 0, 3, 6, 9 and 15, BM and PB samples were obtained. Flow cytometry and
      functional assay were performed to analyze stem cells, subpopulations, adhesion
      molecules, colony-forming units and LTCIC. RESULTS: The total nucleated cells and
      absolute numbers of CD34(+)/mL showed a similar response pattern in both BM and
      PB, with a peak around Day 6 that returned to baseline levels by Day 15. However,
      there was a reciprocal change in the percentage of CD34(+) cells between BM and
      PB compartments. The expressions of adhesion molecule showed an up- and down
      regulation of alpha4 and alpha5 integrin subunits, respectively, also correlated
      with the CD34(+) mobilization patterns. DISCUSSIONS: The functional
      characterization of integrins, and further clinical examination of G-CSF
      stimulated BM is warranted. G-CSF-stimulated BM maybe considered as an
      alternative source of stem cells in transplantation.

PMID- 11953044
TI  - Report of the Tumor Evaluation Committee workshops at ISHAGE 2001.
AB  - Multiple factors impact polymerase chain reaction (PCR) detection of tumor cells
      ranging from the fundamental, such as selection of targets for amplification, to
      the practical, including the timing of sample processing, granulocyte
      contamination and anticoagulant used. Much more work, including standardization
      studies, remains to be performed. Tumor enrichment can be achieved either by
      positive selection, generally by use of antibodies or by depletion of (CD45(+))
      hematopoietic cells. Both approaches work and each has advantages and
      disadvantages. Enriched tumor cells can be further analyzed for expression of
      prognostic markers. A future area of emphasis should be to establish a dialogue
      between practitioners of tumor detection and developers of new therapies who are
      in search of surrogate markers of outcomes.

PMID- 11953043
TI  - Development of a closed-system process for clinical-scale generation of DCs:
      evaluation of two monocyte-enrichment methods and two culture containers.
AB  - BACKGROUND: Clinical immunotherapy trials using DCs depend on large-scale methods
      for DC generation that fulfil current good manufacturing practice requirements.
      Our goal was to develop data on two variables, monocyte-enrichment method and
      culture container, which could be used to design a closed-system process for ex
      vivo generation of immature DCs. METHODS: Mononuclear cells were collected by
      leukapheresis and enriched for monocytes by either counterflow centrifugal
      elutriation, or immunomagnetic selection using Isolex, an automated closed-system
      device. Monocytes were cultured for 7 days in serum-free medium with GM-CSF and
      IL-4, using either plastic flasks or gas-permeable Stericell bags. Monocytes and
      cultured DCs were evaluated for yield, flow cytometric phenotype, and in vitro
      function in MLR, and autologous recall responses to tetanus toxoid and influenza
      virus. RESULTS: Enriched monocyte products from elutriation and immunomagnetic
      selection were equivalent in yield and purity, and were capable of generating
      immature DCs in either flasks or bags. DCs from all four culture conditions were
      equivalent in yield, phenotype, and in vitro function. Mean DC yield was 67-80%
      per seeding monocyte, and 11-13% per starting mononuclear cell (MNC). A
      leukapheresis product containing 5 x 10(9) MNCs processed by this method could
      therefore yield approximately 5 x 10(8) immature DCs. DISCUSSION: In this
      manufacturing process, the Isolex system was equivalent to elutriation, and
      Stericell bags were equivalent to flasks. Together, the Isolex system and
      Stericell bags can be incorporated into a closed-system process to generate
      immature DCs.

PMID- 11953045
TI  - Legal and Regulatory Affairs workshop summary.

PMID- 11953047
TI  - Basic aspects of high-speed sorting for clinical applications.

PMID- 11953048
TI  - Public Meeting and Workshop on 'Safety issues pertaining to the clinical
      application of flow cytometry to human-derived cells'.

PMID- 11953049
TI  - Cell sorting for therapeutic applications - points to consider.

PMID- 11953050
TI  - Identification and isolation of Ag-specific T cells by flow sorting.

PMID- 11953051
TI  - Quantitative flow cytometry: history, practice, theory, consensus, inter
      laboratory variation and present status.

PMID- 11953052
TI  - Immunophenotypic and functional recovery following stem-cell transplantation.

PMID- 11953054
TI  - [Superselective arterial embolization for hemorrhage from malignant gestational
      trophoblastic tumor].
AB  - OBJECTIVE: To evaluate the efficacy of superselective arterial embolization to
      control hemorrhage from malignant gestational trophoblastic tumor. METHODS: From
      February 1990 to June 2001, 31 patients (choriocarcinoma 24, invasive mole 7)
      with hemorrhage from malignant gestational trophoblastic tumor were treated with
      superselective arterial embolization. The hemorrhage organs included uterus (22
      cases), vagina (3 cases), liver (3 cases), bladder (2 cases), and intestine (1
      case). RESULTS: In 28 cases (90.3%), superselective arterial embolization
      successfully controlled the hemorrhage. Hysterectomy was performed in the 3
      failed and uterine perforation was revealed by laprotomy. Four patients had
      normal term delivery after successful superselective arterial embolization and
      chemotherapy. CONCLUSION: Superselective arterial embolization can effectively
      control the hemorrhage from malignant gestational trophoblastic tumor.

PMID- 11953056
TI  - [Clinical observation of transcatheter uterine artery embolization for uterine
      myoma].
AB  - OBJECTIVE: To investigate the efficiency and safety of transcatheter uterine
      artery embolization (TUAE) for uterine myomas. METHODS: Thirty-eight cases of
      uterine myomas were treated by TUAE using lipiodol-pingyangmycin emulsion. 5 of
      38 cases underwent hysterectomy or myomectomy from 1 to 3 weeks after TUAE. The
      specimens were studied pathologically. Thirty-three of 38 patients were followed
      for 3 to 6 months to observe the changes of myoma size and uterine volume and
      overian function. RESULTS: Symptom released in 90.6% (29/32), that was controlled
      of menorrhagia in 90.3% (28/31), disappeared of lumbago and lower abdominal pain
      in 83.3% (25/30), relieved of freguency and urgency of micturition in 45.5%
      (5/11). The mean reduction of myoma and uterine volume at 6 months was 59.1% and
      49.3%, respectively, and at 12 months was 61.8% and 49.9% respectively. There was
      no significant difference in hormone level pre-embolization and post
      embolization. Pathological studies of specimens showed that lipiodol deposition
      was found in myomas but not in myometrium. Myomas occurred spotty necrosis 2
      weeks after embolization and extensive patchy necrosis 3 weeks after
      embolization. Degeneration or necrosis were not seen in myometrium. CONCLUSIONS:
      TUAE possesses a good effect for uterine myomas and doesn't result in the damage
      of ovarian hormone secretion and the myometrium.

PMID- 11953055
TI  - [Clinical analysis of 42 cases uterine myoma by uterine arterial embolization].
AB  - OBJECTIVE: To assess the clinical effects and side effects of uterine arterial
      embolization (UAE) on uterine myoma. METHODS: UAE was performed in 42 patients
      with uterine myoma. The 4 approximately 5 F cobra catheters were insered into the
      uterine arteries for treatment. Gelfoam particles mixed with antibiotics were
      used to embolize the arteries. All patients were followed upto 18 monthes post
      operation. RESULTS: Arteriography showed that uterine myoma was mainly supplied
      by uterine arteries and partly by ovarian arteries. All clinical symptoms of 42
      patients were relieved. Menorrhagia was reduced 26.3% approximately 75.2%. The
      volume of uterus myoma decreased 77.7% and 83.0% 12 and 18 months after UAE,
      respectively and the volume of uterine decreased 54.9% and 62.7%. CONCLUSIONS:
      UAE was an effective and satisfactory method for the treatment of uterine myoma.
      Further effects of it should be observed continuously and periodically.

PMID- 11953057
TI  - [Study of the role of calcitonin during the embryo implantation].
AB  - OBJECTIVE: To observe the role of calcitonin (CT) during the implantation.
      METHODS: Human endometrial epithelial cells were cultured. After stimulated with
      various concentrations of CT, intracellular calcium (Ca(2+)) in the epithelial
      and stroma cells and pre-embryos were measured by the laser scanning confocal
      microscope. RESULTS: When stimulated with different concentrations of CT, mean
      fluorescence levels in the epithelial cells were similar to that of the control.
      However CT can improve intracellar Ca(2+) of preimplantation embryos and stroma
      cells in a dose-dependent manner and significantly higher than those of controls.
      When 10 nmol/L CT was added to the culture medium, the intracellular Ca(2+)
      concentration in 8-cell embryos rose immediately. Embryo exposure to CT was
      followed by a series of Ca(2+) bursts that persisted for at least 2 hours. No
      change in Ca(2+) was observed when culture medium alone was added to the embryos.
      Pre-loading embryos and stoma cells with the Ca(2+) chelator, prevented the
      increased fluorescence after CT addition. CONCLUSIONS: CT play an important role
      during the procesess of implantation. It maybe improve intracellar of preembryos
      and accerate the development of preembryos.

PMID- 11953058
TI  - [Quantitation of hepatitis C virus RNA in amniotic fluid of gravida infected by
      hepatitis C virus].
AB  - OBJECTIVE: To detect hepatitis C virus (HCV) RNA in amniotic fluid of gravida and
      investigate mother-to-infant transmission of HCV. METHODS: Thirty-four HCV
      seropositive gravida (experimental group) were engaged. Fluorescence quantitative
      polymerase chain reaction (PCR) based on amplisensor assay and reverse
      transcription -PCR (RT-nPCR) was used. Serum HCV RNA positive sera were genotyped
      by RFLP analysis of PCR products from 5'NC region. Sera and amniotic fluid
      samples of 40 normal gravida were set as the control group. RESULTS: In the
      experimental group, HCV RNA was detected in amniotic fluid (5.9%, 2/34) of 2
      cases. HCV RNA titers were 10(5) and 10(6) copy/ml respectively. No HCV RNA was
      detected in the amniotic fluid and sera of the control (n = 40). CONCLUSIONS: HCV
      RNA was rarely detected in amniotic fluid. The amniotic fluid is not the main
      route of HCV mother-to-infant transmission.

PMID- 11953059
TI  - [Expression and role of placental vascular endothelial growth factor in patients
      with pregnancy induced hypertension].
AB  - OBJECTIVE: To investigate the expression of placental vascular endothelial growth
      factor (VEGF) and its relationship with construction of placental vascular
      network, placental weight and the newborns' weight in patients with pregnancy
      induced hypertension (PIH). METHODS: Twenty-five patients with PIH and twenty
      five normal late pregnant (NLP) women in the third trimester were observed in
      this study. The expression of VEGF protein in placental, the placental vascular
      density were determined by Western blot and immunohistochemical F8 staining
      respectively. RESULTS: The VEGF values in patients with PIH and NLP were 24 793
      +/- 6 579 and 41 903 +/- 11 009, and the vascular densities were (61 +/- 11) and
      (78 +/- 11) counts/400 x vision respectively. They were both significantly
      different in both groups and were closely related to the severity of PIH (P <
      0.01). Placental weight and the newborns' weight in patients with PIH [(460 +/-
      59) g, (3 176 +/- 503) g respectively] were also significantly decreased compared
      with NLP [(573 +/- 99) g, (3 468 +/- 493) g respectively], but the new newborns'
      length had no significant difference between the two groups (P > 0.05). In NLP
      group, placental vascular density, placental weight and the newborns' weight all
      had a significantly positive correlation with VEGF (P < 0.01, r = 0.823, 0.671,
      0.888 respectively) and in PIH group, the situation was the same (P < 0.01, r =
      0.905, 0.859, 0.732 respectively), but the new newborns' length had no
      correlation with VEGF (P > 0.05). CONCLUSION: It shows that the reduced
      expression of VEGF in placenta of patients with PIH may be one of the important
      factors responsible for decreased placental vascular density and fetal
      intrauterine growth restriction.

PMID- 11953060
TI  - [Analysis of prophylactic antibiotics for cesarean section].
AB  - OBJECTIVE: To study the appropriate antibiotic for prophylactic use in cesarean
      section. METHODS: The effects and side effects of prophylatic antibiotics in 1
      266 cesarean section were studied retrospectively. Six regiems were engaged: (1)
      Penicillin and Ampicillin; (2) Mezlocillin sodium; (3) Sulbactam and Ampicillin;
      (4) Ciprofloxacin; (5) Clindamycin; (6) Cefacidal. RESULTS: The duration of
      postoperative body temperature return to normal of 1 - 6 group is (54.0 +/- 28.4)
      hours, (48.9 +/- 27.8) hours, (49.9 +/- 23.9) hours, (58.6 +/- 33.7) hours, (52.5
      +/- 25.2) hours, (63.1 +/- 51.1) hours respectively. It was longer in cefazolin
      group than the others. There were less puerperal morbidity and side effects of
      Mezlocillin. CONCLUSIONS: Penicillin and Ampicillin are still the most common
      choices as prophylatic antibiotic in cesarean section. Mezlocillin is appropriate
      as well.

PMID- 11953061
TI  - [Feasibility study of intra-utero surgical repair of fetal lamb].
AB  - OBJECTIVE: To evaluate the feasibility of intra-utero fetal lamb surgical repair.
      METHODS: Six twin lambs underwent surgery intra-utero at 112 days of gestation
      (term 140 approximately 160 days). After maternal laparotomy and Hysterotomy,
      fetal lamb's toe was excised or its cleft lip was repaired in one of twin.
      RESULTS: At 30 to 32 days post operation, five lambs were spontamcously delivered
      and the other was cesarean delivery to full term gestation. Fetal wounds healed
      without inflammation and scar formation. CONCLUSIONS: The methods of fetal lamb
      intro utero surgical repair is feasible.

PMID- 11953062
TI  - [Expression of HOXA10 gene in human endometrium and its relationship with
      unexplained infertility].
AB  - OBJECTIVE: To study the expression of HOXA10 gene in the endometrium of normal
      fertile women and patients with unexplained infertility during different phases
      of menstrual cycle. METHODS: Endometrium samples were obtained by curettage in 52
      normal fertile women and 38 patients with unexplained infertility during
      different phases of menstrual cycle, HOXA10 mRNA expression were detected by in
      situ hybridization and reverse polymerase chain reaction (RT-PCR). RESULTS: (1)
      HOXA10 mRNA were detected in the glandular and stromal cells of endometrium of
      fertile women during the menstrual cycle. By in situ hybridization (positive
      unite, PU), HOXA10 mRNA levels were significantly higher in the mid-secretory
      phase [glandular cells (G) 5.69 +/- 0.57, stromal cells (S) 7.48 +/- 0.67] and
      late-secretory phase(G 5.99 +/- 0.40, S 7.98 +/- 1.08) than those in late
      proliferative phase (G 3.35 +/- 0.20, S 3.20 +/- 0.37) and early secretory phase
      (G 3.07 +/- 0.26, S 3.18 +/- 0.27)(P < 0.01). HOXA10 mRNA levels of endometrial
      stromal cells of mid and late secretory were higher than those of glandular cells
      (P < 0.01). By RT-PCR, HOXA10 mRNA levels were significantly higher in the mid
      secretory phase (57.0 +/- 3.4)% and late secretory phase (56.2 +/- 2.9)% than
      those in early proliferative phase (31.8 +/- 2.6)%, late proliferative phase
      (32.2 +/- 2.3)% and early secretory phase (32.5 +/- 1.6)% (P < 0.01). (2)
      Patients with unexplained infertility did not have an increase of endometrial
      HOXA10 mRNA level in mid and late secretory phase, as compared with the controls
      (P < 0.01). CONCLUSIONS: (1) High expression of HOXA10 gene during mid and late
      secretory phase indicated that HOXA10 gene may involve in implantation. (2)
      Aberrant HOXA10 expression of patients with unexplained infertility suggests that
      altered development of endometrium at the molecular level may contribute to the
      aetiology of infertility. (3) HOXA10 gene may play a role in decidua lization of
      endometrium during early pregnancy.

PMID- 11953063
TI  - [Establishment and biological characteristics of nude mice xenograft tumor models
      of human endometrial carcinoma].
AB  - OBJECTIVE: To establish nude mice xenograft tumor models of human endometrial
      carcinoma for basic and clinical study. METHODS: Fourteen samples of human
      endometrial carcinoma were subcutaneously heterotransplanted to nude mice
      (BALB/C, nu/nu), 3 approximately 4 mice were transplanted for every sample.
      RESULTS: The initial take rate was 42.8%, then it increased to 100.0% after the
      5th passage. Five of 14 samples were transplanted for 48 approximately 63
      passages. The characteristics of histology, ultrastructure and chromosome were
      identical to those of human donor tumors. The DNA ploidy was consistent for SL-1,
      SL-2 and SL-3, but changed for SL-4 and SL-5 by cytometric analysis. The
      expression of estrogen receptor and progesterone receptor for 5 models was all
      negative. The expression of p53 was positive for SL-1, SL-2 and SL-4, but
      negative for SL-3 and SL-5. The expression of c-erbB-2 was positive for SL-1, SL
      2 and SL-4, negative for SL-3 and SL-5. The expression of p16 was positive for SL
      2 and SL-3, negative for SL-1, SL-4 and SL-5. CONCLUSIONS: Five nude mice
      xenograft tumor models of human endometrial carcinoma were established
      successfully. It will be helpful for the basic and clinical study of human
      endometrial carcinoma.

PMID- 11953064
TI  - [A study on the relationship between insulin-like growth factor, insulin-like
      growth factor-binding protein-3 and fetal growth retardation].
AB  - OBJECTIVE: To explore the effect of insulin-like growth factor-I (IGF-I), insulin
      like growth factor-II (IGF-II) and insulin-like growth factor-binding protein-3
      (IGFBP-3) on the fetal growth. METHODS: Samples of maternal blood and matched
      umbilical cord blood were collected at time of delivery from twenty pairs of
      mothers and newborns with normal birth weight (control group) twenty pairs with
      fetal growth restriction (FGR group) and ten pairs with macrosomia (macrosomia
      group). Serum IGF-I, IGF-II and IGFBP-3 were measured by radioimmunoassay (RIA)
      and immunoradiometric analysis (IRMA). RESULTS: (1) Levels of maternal serum IGF
      I, IGF-II and IGFBP-3 in GFR group were (130.5 +/- 26.0) microgram/L, (2.40 +/-
      0.42) microgram/L, (5 579 +/- 848) microgram/L respectively; IGF-I, IGF-II and
      IGFBP-3 levels of fetal serum in this group were (6.6 +/- 1.7) microgram/L, (1.54
      +/- 0.31) microgram/L, (869 +/- 183) microgram/L respectively. (2) In macrosomia
      group the levels of maternal serum IGF-I, IGF-II and IGFBP-3 were (309.7 +/-
      44.6) microgram/L, (2.43 +/- 0.25) microgram/L, (5 562 +/- 742) microgram/L
      respectively. In fetal serum that were (69.6 +/- 23.9) microgram/L, (2.19 +/-
      0.29) microgram/L, (1 682 +/- 130) microgram/L respectively. (3) In control group
      the levels of maternal serum IGF-I, IGF-II and IGFBP-3 were (307.9 +/- 70.7)
      microgram/L, (2.41 +/- 0.36) microgram/L, (5 586 +/- 678) microgram/L
      respectively;That were (68.9 +/- 32.9) microgram/L, (1.95 +/- 0.26) microgram/L,
      (1 624 +/- 296) microgram/L in fetal serum respectively. (4) In three group the
      levels of maternal IGF-I, IGF-II and IGFBP-3 were significantly higher than that
      of fetal levels (P < 0.01). The fetal IGF-I, IGF-II and IGFBP-3 levels in FGR
      group were significantly lower than those in control group (P < 0.01). (5) The
      levels of fetal IGF-I, IGF-II, IGFBP-3 were positively correlated with birth
      weight (r = 0.61, r = 0.51 and 0.63, P < 0.01) and placental weight (r = 0.47, r
      = 0.56 and 0.48, P < 0.01). The levels of fetal IGF-I, IGF-II and IGFBP-3 were no
      different between macrosomia group and control group. CONCLUSIONS: This study
      suggest that (1) IGF-I, IGF-II and IGFBP-3 cannot pass through the placenta. (2)
      The betal IGF-I, IGF-II and IGFBP-3 may have the close relationship with the
      fetal growth. The decrease of IGF-I, IGF-II and IGFBP-3 may be one of the causes
      of FGR.

PMID- 11953065
TI  - [Comparison study on uterine and umbilical artery blood flow during pregnancy at
      high altitude and at low altitude].
AB  - OBJECTIVE: To evaluate the effect of high altitude on uterine and umbilical
      artery blood flow dynamics during normal pregnancy. METHOD: Uterine artery blood
      flow parameters of the pregnant (34) and nonpregnant (37) subjects and umbilical
      artery blood flow parameters of 119 subjects living at high altitude or at low
      altitude were measured with color Doppler flow imaging system. RESULTS: Uterine
      artery diameter, blood flow volume increased during pregnancy at both altitude,
      and uterine artery blood flow volume and diameter were smaller at high altitude
      than at low altitude [(0.35 +/- 0.04) cm vs (0.45 +/- 0.04) cm, (280 +/- 48)
      ml/min vs (425 +/- 55) ml/min, P < 0.01]. Umbilical artery blood flow velocity
      systolic to diastolic (S/D) value, resistant index of different pregnant period
      were greater at high altitude than at low altitude (P < 0.01). CONCLUSION: High
      altitude has effect on placental and infant blood flow that causes the decrease
      of placental blood infusion and the increase of uterine and umbilical artery flow
      velocity S/D and reactive index.

PMID- 11953066
TI  - [Effects of recombinant human leukemia inhibitor on the preimplantation mouse
      embryo development in vitro].
AB  - OBJECTIVE: To assess the effect of recombinant human leukemia inhibitory factor
      (rhLIF) on mouse embryo development in vitro. METHODS: Mice were randomly divided
      to three groups, one in vivo control (group I) and two in vitro (group II and
      III). Mice were sacrificed at 116 - 120 hours (group I) and 44 - 48 hours (group
      II and III) subsequent human chorionic gonadotropin (hCG) injection. Two-cell
      embryos (group II and III) and blastocysts (group I) were obtained. Embryos in
      group II were cocultured with human tubal fluid (HTF) + 10% human serum and in
      group III with HTF + 10% human serum + rhLIF (1 000 U/ml). The number of embryo
      in different stage was recorded and compared. RESULTS: Embryo in four, eight-cell
      and morula was noted in group II and III, 87.7% versus 91.2% and 75.0% versus
      85.4% respectively. There was no significant difference. However, further embryo
      development to the blastocyst, expanded blastocyst, and hatching blastocyst in
      group II (48.1%, 32.1% and 18.4%) was lower than that in group III (82.3%, 59.7%
      and 36.3%). There was no difference between blastocyst in group I and group III
      (86.0% vs 82.3%). CONCLUSION: RhLIF does not provide obvious stimulation in early
      mouse embryo, however, rhLIF can promote the growth, differentiation, and
      hatching of preimplantion blastocyst.

PMID- 11953067
TI  - [Effect of cyclosporin A on the growth of human first trimester cytotrophoblasts
      in vitro].
AB  - OBJECTIVE: To investigate effect of cyclosporin A (CsA) on the growth of first
      trimester human cytotrophoblast in vitro. METHODS: To isolate and purificate
      first trimester human cytotrophoblasts by way of percoll density gradient
      centrifugation; to evaluate the effect of CsA on in vitro proliferation of
      cytotrophoblasts using (3)H-thymidine incorporation assay; to analyze of cell
      cycle of cytotrophoblasts with flow cytometric assay; and to survey morphology of
      the cells by scanning electro-microscope respectively. RESULTS: CsA could
      increase in vitro proliferation of first trimester human cytotrophoblasts when
      concentration of CsA ranged from 1 x 10(-4) micromol/L to 1 micromol/L, but
      decrease in vitro proliferation of the cells if the concentration reached to 10
      micromol/L. G(2)-M phase increased from (2.8 +/- 0.5)% to (6.7 +/- 1.3)% when the
      cytotrophoblasts were incubated with culture medium containing 1 micromol/L CsA
      for 24 hours, while S phase increased from (14 +/- 5)% to (28 +/- 8)% and
      apoptosis decreased from (8.7 +/- 2.2)% to (3.6 +/- 1.0)% when the culture in the
      same incubating condition lasted for 48 hours. Pseudopodia of the trophoblasts
      increased in number and length when they were incubated in culture medium
      containing 1 micromol/L of CsA for 48 hours, but decreased if the concentration
      reached to 10 micromol/L with the same incubating duration. CONCLUSION: CsA is
      able to promote growth of first trimester human cytotrophoblasts and change their
      morphology, which appears to increase in invasive ability.

PMID- 11953068
TI  - [Uterine arterial embolization in the treatment of adenomyosis].
AB  - OBJECTIVE: To assess the clinical efficacy of uterine arterial embolization (UAE)
      in the treatment of adenomyosis. METHODS: UAE procedures were performed in 23
      patients with adenomyosis. Two 3.0 F FASTRACKER-325 tubes were placed into
      bilateral uterine arteries respectively and the fresh gelfoam particles mixed
      with antibiotic drugs were used to embolise the arteries. After treatment the
      symptoms and uterine volume of all patients were investigated. RESULTS: All
      clinical symptoms of 23 patients relieved. Dysmenorrhea completely disappeared in
      19 patients, significantly alleviated in 2 patients. But in other 2 recurred. The
      uterine volume shrunk significantly [(50 +/- 18)%] vs [(100 +/- 0)%]. The blood
      flow within the uterine and lesions detect by color doppler flow imaging
      decreased immediately after UAE. Low-abdominal pain and slight fever were seen
      after treatment and recovered within 1 - 2 weeks. CONCLUSION: UAE is an effective
      and safe method in the treatment of adenomyosis.

PMID- 11953069
TI  - [Clinical analysis of 11 cases with perineal endometriosis].
AB  - OBJECTIVE: To report the diagnosis and treatment of 11 cases with perineal
      endometriosis (PE). METHODS: Eleven patients with PE treated in our department
      from 1983 - 2000 years were analyzed retrospectively and were followed for 0.5 -
      7.0 years. RESULTS: The incidence of PE is 0.37% of total endometriosis cases
      operated in our department or 0.087 per thousand of total episiotomy undergone in
      our delivery room during the 18 year period. Their diagnosis were confirmed
      clinical manifestations and pathological evidences. All except one had history of
      perineal tear and episiotomy. The latent period of patient who was less than 30
      years old is within one year. The latent period of patient who was more than 30
      years old is more than one years (P < 0.05). Complete surgical excision with a
      cure rate of 91% (10/11). CONCLUSIONS: PE is mainly diagnosed by clinical
      manifestations. Surgical excision is the first choice of treatment.

PMID- 11953070
TI  - [One year observation on effects of estrogen, tamoxifen combined with or without
      fluoride on preventing bone loss in ovariectomized rats].
AB  - OBJECTIVE: To compare the effects of one year treatment of estrogen and
      tamoxifen, either alone or combined with fluoride on bone metabolism in
      ovariectomized rats. METHODS: One hundred and forty two virgin female Sprague
      Dawley rats were ovariectomized (OVX) or sham operated at 6 months of age, and
      randomly divided into 7 groups (19 - 21 rats each): (1) sham-operated controls;
      (2) OVX vehicle controls; (3) estrogen group; (4) fluoride group; (5) tamoxifen
      group; (6) fluoride plus estrogen; (7) fluoride plus tamoxifen. The treatments
      lasted for one year. Bone mineral density (BMD) measurement, bone
      histomorphometry analysis (lumbar vertebrae) and biomechanical test (3-point
      bending test on right femur) were performed before and after treatment. The
      histological change of uterus were also determined at the same time. RESULTS: (1)
      Twelve months of ovariectomy, the OVX group had significantly lower total body
      (279 mg/cm(2)), lumbar vertebra (232 mg/cm(2)) than all other groups (total body
      286 - 298 mg/cm(2), lumber 251 - 266 mg/cm(2), P < 0.05). Estrogen group (216
      mg/cm(2)) had higher BMD than tamoxifene group (195 mg/cm(2)) in midshaft of
      femur. (2) After 4 months of ovariectomy, only the two combination groups kept
      the maximum load (145 N) of right femur over the level of OVX group (118 N);
      after 12 months of treatment, the maximum load of OVX group [(108 +/- 13) N] was
      significantly different from all other groups (132 - 155 N); both maximum load
      and elastic load of estrogen group were significantly higher than that of
      tamoxifen group. (3) No evidence of dysmineralization was found by bone
      histomorphometry. CONCLUSIONS: Estrogen has more potent effects on keeping bone
      mass and bone strength as compared with tamoxifene. The combined therapy
      (estrogen + fluoride or tamoxifen + fluoride) resulted in better bone strength
      than the single ones.

PMID- 11953071
TI  - [Effects of metformin on the plasminogen activator system, endocrine, metabolic
      profiles in patients with polycystic ovary syndrome and clomiphene resistant
      cases].
AB  - OBJECTIVE: To assess the therapeutic effects of metformin in patients with
      polycystic ovary syndrome (PCOS) and clomiphene (CC) resistant cases. METHODS:
      Thirty one patients with PCOS, including 8 CC resistant cases were studied. Serum
      tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1
      (PAI-1), menstrual and reproductive hormone patterns, lipid and glucose metabolic
      parameters, bilateral ovarian volume, side effects were determined before and
      after oral administration of metformin 375 mg three times daily for 12 - 16
      weeks. Metformin and CC were co-administered in CC resistant cases who had not
      restored their menstrual cycle after the treatment with metformin alone for
      investigating ovulation rate. In the remaining non-CC resistant metformin failure
      cases the dosage of metformin was incrersed to 500 mg three times daily for
      investigating menstrual cycle. RESULTS: After administration of metformin for 12 
      16 weeks, serum PAI-1, luteinizing hormone (LH)/follicle stimulating hormone
      (FSH) ratio, androstenedione, testosterone, low density liproprotein-cholesterol,
      total cholesterol, fasting insulin concentration and response to oral glucose
      tolerant test (OGTT), diastolic blood pressure decreased significantly, while FSH
      and estradiol levels increased, bilateral ovarian volume shrunk significantly (P
      < 0.05 - 0.01). Body mass index, waist hip ratio, LH, tPA, systolic blood
      pressure, prolactin, fasting glucose concentration and response to OGTT, high
      density liproprotein-cholesterol, apoliprotein A, apoliprotein B, triglycerides
      levels did not change significantly (P > 0.05). Nineteen out of thirty one cases
      (61%) had restoration of menstrual cycle, 2 became pregnant. In 6 CC resistant
      cases who had not restoration of menstrual cycle after the treatment with
      metformin, CC induced ovulation in 12/18 cycles or 5/6 cases and 2 pregnancies
      achieved. In others 6 metformin failure cases the dosage of metformin was
      increased to 500 mg three times daily, one restored menstrual cycle and became
      pregnant. CONCLUSIONS: Metformin may ameliorate the PAI-1, endocrine, metabolic
      profiles and menstrual abnormalities and improve the ovarian response to CC in CC
      resistant cases. Metformin provides a safe and effective approach to the
      treatment of PCOS.

PMID- 11953072
TI  - [Influence of surgical methods on survival and recurrence of stage I endometrial
      carcinoma].
AB  - OBJECTIVE: To determine the influence of different surgical procedure on post
      operative survival rate and recurrence of stage I endometrial carcinoma. METHODS:
      From 1986 to 1996, 110 patients with stage I endometrial carcinoma surgically
      treated in our hospital were studied retrospectively. They were divided into
      three groups, including total hysterectomy plus bilateral salpingo-oophorectomy
      (group A), radical or modified radical hysterectomy (group B) and total
      hysterectomy plus bilateral salpingo-oophorectomy or radical hysterectomy or
      modified radical hysterectomy + pelvic lymphadenectomy (group C). Survival and
      recurrent rates were analysed according to the follow-up data. RESULTS: Five-year
      survival rate of the three groups are 89.5%, 90.5% and 95.1% respectively (P >
      0.05). Of the 71 cases followed up for more than two years, 9 relapsed. The
      recurrent rates were 12.7%. Seven relapsed within three years after operation.
      Eight patients had local recurrence and 5 had distant metastasis. Recurrent rates
      of three groups are 13.9%, 9.1% and 12.5% (P > 0.05), local recurrent rates are
      13.9%, 9.1% and 8.3% (P > 0.05), distant metastasis rates are 2.8%, 9.1% and
      12.5% respectively (P > 0.05) with no statistical significance. CONCLUSIONS:
      Surgical method is not the main factor influenced the survive of stage I
      endometrial carcinoma. Radical operation or lymphadenectomy will not increase the
      survival rate of stage I endometrial carcinoma significantly. The purpose of such
      operation is to find out the exact stage and the possible prognosis. Distant
      metastasis is remarkable, and should be considered in the adjuvant therapy.

PMID- 11953073
TI  - [Outcome with intracavitary high-dose-rate brachytherapy for primary vaginal
      cancer].
AB  - OBJECTIVE: To evaluate the efficacy of radiation therapy on primary vaginal
      cancer with high-dose-rate brachytherapy alone or in combination with external
      radiation. METHODS: Fifty one cases with primary vaginal cancer who were treated
      with high-dose-rate brachytherapy alone or in combination with the external
      radiation in Cancer Hospital, Chinese Academy of Medical Sciences from 1989 to
      1999 were retrospectively studied, including stage I 10 cases, stage II 13 cases,
      stage III 23 cases and stage IV 5 cases. WD-HDR18 after-loading equipment was
      used in the brachytherapy and 6 or 8 MV linear accelerator was used in the
      external radiation. RESULTS: The overall 5-year survival rate with WD-HDR18 was
      58.8%, with 80.0% for stage I, 76.9% for stage II, 65.2% for stage III, and 0.0%
      for stage IV. The comparison of treatments with WD-HDR18 and radium therapy
      showed the 5-year survival rates of the cases of each stage treated with WD-HDR18
      were higher. CONCLUSION: Treatment results obtained with high-dose-rate
      brachytherapy are at least similar to traditional radium therapy for primary
      vaginal cancer.

PMID- 11953075
TI  - [Clinical analysis of 74 cases with ovarian thecoma].
AB  - OBJECTIVE: To study the clinical pathologic characteristics, treatment and
      prognostic factors of ovarian thecoma. METHODS: From 1958 approximately 1998, a
      total of 74 patients with benign and malignant thecoma were retrospectively
      analyzed. RESULTS: The reviewed diagnosis were 8 patients with malignant thecoma,
      66 patients were benign thecoma. Nine of 66 patients with benign thecoma appeared
      cell proliferative activity. The mean age was 52 years. The most frequent
      symptoms were abdominal-pelvic masses (56.8%), metromenorrhagia and abnormal
      vaginal bleeding, other symptoms were abdominal pain, infertility followed.
      Twenty-two of 66 patients had ascites, only 1 patient with ascites and
      hydrothorax simultaneously. Thirty-nine patients with diseases which associate
      with excessive estrogenic stimulation, including 1 endometrial adenocarcinoma and
      1 endometrial dysplasia and other diseases such as: myoma; endometrial
      hyperplasia and polyp. Fifteen patients with benign thecoma were evaluated blood
      serum CA(125), the CA(125) were elevated in 9 of 15 patients. In 2 of 9 patients
      with cell proliferative activity, the tumors invaded adjacent tissues or
      relapsed, after received operation and pelvic radiotherapy, they are alive 11
      years and 27 years respectively. Among 8 patients with malignant thecoma, 4
      patients without postoperation therapy or with non-standard chemotherapy died in
      2 years postoperation, the other 4 patients received operation, postoperational
      radiotherapy or (and) chemotherapy, 1 of 4 patients died of irradiation
      intestinal fistule 4 years later; two patients are alive without disease more
      than 10 years, another one for 2 years. CONCLUSIONS: Theca cell tumor of ovary
      have good prognosis, but we should pay attention to thecomas with proliferative
      activity. The prognosis of malignant thecomas is poor, postoperative systemic
      chemotherapy or radiotherapy to the patients with malignant thecomas can improve
      their survival.

PMID- 11953074
TI  - [Histological classification in 10 288 cases of ovarian malignant tumors in
      China].
AB  - OBJECTIVE: The histological types of ovarian tumors were investigated and
      analyzed in China in order to compare with those in other countries, which will
      benefit to the prevention and treatment of ovarian carcinoma. METHODS: The
      pathological data from 42 197 cases of ovarian tumors in ten years during 1980 to
      1989 were registered according to the WHO classification for ovarian tumors. Some
      unsure cases pathologically in the previous diagnosis should be reconfirmed
      according to the WHO classification. RESULTS: Forty-two thousand one hundred and
      ninety seven cases of ovarian tumors were selected from all tumors in 21
      provinces and 3 major regional cities in China. There were 10 288 (24.4%)
      malignant tumors in all cases. They were composed by 5 650 (54.9%) cases of
      epithelial tumors, 1 871 (18.2%) cases of germ cell tumors, 873 (8.5%) cases of
      sex cord tumors, 1 003 (9.7%) cases of secondary tumors, and 891 (8.7%) cases of
      other tumors. The malignant tumors constituent ratios were 52.8% and 47.2%
      respectively in the north and south of the Yangtze River. The histological types
      of ovarian tumors were about the same ratios, but the malignant tumors were
      different in Chinese 6 major administrative region and also in the region both
      north and south of the Yangtze River. The ratio of borderline epithelial ovarian
      tumors to epithelial carcinoma was 1.0:5.9. Borderline serous cystadenocarcinoma
      appeared to be similar to borderline mucinous cystadenocarcinoma in frequency.
      Serous cystadenocarcinoma was found to be the most frequent one in malignant
      epithelial tumors. CONCLUSIONS: Compared with reports abroad, the different types
      of malignant ovarian tumors in China represent a different distributive pattern.
      The malignant epithelial ovarian tumors were lower than that in other countries,
      while the malignant germ cell tumors and sex cord stromal tumors were 6 and 3
      times higher than those abroad, the main metastasizing tumors come from
      gastroenteric carcinoma.

PMID- 11953076
TI  - [Experimental study on sulindac metabolites -induced apoptosis on human umbilical
      vein endothelial cell line ECV304].
AB  - OBJECTIVE: To investigate the effects of sulindac metabolites on the
      proliferation and apoptosis of human umbilical vein endothelial cell line ECV304
      in vitro. METHODS: The proliferation of ECV304 was determined by methyl thiazolyl
      tetrazolium (MTT) method. The cell cycle, apoptosis and the ultrastructure of
      ECV304 were detected by flow cytometry (FCM) and electron microscopy
      respectively. RESULTS: MTT assay showed that sulfide inhibited the proliferation
      of ECV304, and the effects was dose-dependent, the 50% inhibiting concentration
      (IC(50)) was 200 micromol/L. FCM showed that sulfide changed cell cycle
      distribution, the cell cycle were: Go-G(1) phase [control group (77.7 +/- 1.6)%,
      sulfone group (75.6 +/- 2.1)%, sulfide group (46.1 +/- 1.6)%]. S phase [control
      group (13.6 +/- 1.2)%, sulfone group (16.4 +/- 2.3)%, sulfide group (27.3 +/-
      2.1)%], G(2)-M phase [control group (8.6 +/- 0.7)%, sulfone group (8.0 +/- 0.5)%,
      sulfide group (26.6 +/- 3.5)%]. The apoptosis rates in control group, sulfone
      group and sulfide group were (6.1 +/- 3.4)%, (4.8 +/- 2.1)% and (51.9 +/- 5.7)%,
      respectively. Compared with the control group, sulfide can reduce the proportion
      of G(1) phase, increase the proportion of S phase and G(2)-M phase significantly
      (P < 0.01). Also sulfide induce cell apoptosis significantly (P < 0.01). In the
      sulfide-treated cells, chromatin concentration, cytomembrane shrinkage,
      neighboring cell detachment, and apaptolic body were observed. Sulfone has no
      effect on cell proliferation, cell cycle and cell morphology. CONCLUSIONS:
      Sulfide can reduce the viability of ECV304, change the cell cycle distribution,
      arrest the cell cycle in G(2)-M phase and induce apoptosis. Sulfone didnet.

PMID- 11953077
TI  - [Clinical effect and mechanism of nitroglycerin patch on arresting preterm
      labor].
AB  - OBJECTIVE: To observe the effect of nitroglycerin patch on treatment of preterm
      labour and to identify the mechanism responsible for arrest of preterm labour
      with nitroglycerin patch. METHODS: Sixty women diagnosed as threatened preterm
      labour were divided into two groups: group of nitroglycerin patch therapy (n =
      30), and group of magnesium sulfate and salbutamol sulfate therapy (n = 30).
      Nitroglycerin patch was applied to the abdomen of patients. Measurement of
      cortictrophin-releasing hormone (CRH) levels in maternal plasma was performed by
      radioimmunoassay. RESULTS: The mean time of pregnancy prolongation was 25 days in
      the nitroglycerin patch group, and 8 days in the magnesium sulfate and salbutamol
      sulfate group. The mean level of CRH concentration in nitroglycerin patch group
      before treatment was (257 +/- 61) ng/L, and it was decreased sharply to (38 +/-
      17) ng/L after treatment. Those were (248 +/- 60) ng/L and (56 +/- 22) ng/L
      respectively in the magnesium sulfate and salbutamol sulfate group. CONCLUSION:
      Reduction of CRH secretion may be the mechanism of nitroglycerin patch on preterm
      labour therapy. It may act as an effective, safe, well-tolerated, and non
      invasive method for treatment of preterm labour.

PMID- 11953078
TI  - [Effect of intrauterine hepatitis B virus infection on hepatitis B vaccine
      inoculation in newborns].
AB  - OBJECTIVES: To study the effect and the mechanism of peripheral blood nuclear
      cells (PBMC) invaded by hepatitis B virus (HBV) on the artificial immunization in
      newborns. METHODS: Fifty-two newborns, whose mothers were hepatitis B surface
      antigen (HBsAg) positive, were immunized with hepatitis B immunoglobulin and
      hepatitis B vaccine (HBVac), and then followed for 7 months. The newborns' serum
      and PBMC HBV DNA was detected by nested-PCR, hepatitis B surface antibody (HBsAb)
      was tested with solid phase radioimmunoassay. PBMC from newborn were incubated
      with PHA and HBsAg. The supernatant interleukin 2 (IL-2) level was measured by
      enzyme linked immununosorbent assay (ELISA). RESULTS: The rate of vaccination
      failure was higher in the infants with PBMC HBV DNA positive than those with
      negative (P < 0.05). The supernatant IL-2 level was lower in the former than that
      in the latter and the control (P < 0.05). The level of IL-2 in the immunization
      failure newborns was lower than that in the vaccination success and the control
      (P < 0.05). CONCLUSIONS: The intrauterine PBMC HBV invasion is one of the
      important causes of vaccination failure in the newborns. PBMC IL-2 autocrine down
      regulation is closely related to HBV invasion, that may lead to the failure of
      HBVac inoculation in the newborns.

PMID- 11953079
TI  - [Outcome of pregnancy with systemic lupus erythematosus treated with DNA
      immunoabsorbent].
AB  - OBJECTIVE: To study the outcome of pregnancy with systemic lupus erythematosus
      (SLE) treated by DNA immunoabsorbent therapy. METHODS: Sixty nine SLE women with
      pregnancy were randomly enrolled into DNA immunoabsorbent group (35, group I) and
      common therapeutic group (34, group II) as control. Outcomes of pregnancy and
      complications were analyzed. RESULTS: The incidence of complication and fetus
      loss in group I was 28.6% (10 cases) and 20.0% (7 cases), while 85.3% (29 cases)
      and 58.8% (20 cases) in group II, there was very significant difference
      respectively (P < 0.01). The incidence of premature birth was 8.6% (3 cases) in
      group I, 26.5% (9 cases) in group II, the difference was significant (P < 0.05).
      CONCLUSION: DNA immunoabsorbent was more efficient than common therapy in the
      management of SLE with pregnancy.

PMID- 11953080
TI  - [Study on expression of norepinephrine and dopamine placental tissues of normal
      pregnancy and pregnancy induced hypertension syndrome].
AB  - OBJECTIVE: To study the distribution and levels of norepinephrine (NE) and
      dopamine (DA) in placenta tissues of normal pregnancy and pregnancy induced
      hypertension syndrome (PIH) and discuss the relationship of NE and DA with PIH.
      METHOD: Control group was consisted of thirty-one normal pregnancies divided into
      three stages (early, middle and late). Study group was consisted of thirty-eight
      women with PIH in mild, moderate and severe degrees. The distribution and levels
      of NE and DA in the placental tissues were detected by immunohistochemistry (SP)
      and computer image analysis. RESULTS: (1) In the control group, the levels of NE
      and DA located in the cell membrane and cytoplasm of cytotrophoblast were higher
      in early pregnancy than that located in the cell membrane and cytoplasm of
      syncytiotrophoblast and endothelium of capillary vessel in middle and late
      stages. The results in PIH were same as late stage in control group. (2) The
      expression of NE (1.595 +/- 0.018) and DA (1.552 +/- 0.067) were decreased
      gradually in early pregnancy than that of NE (1.488 +/- 0.019, 1.419 +/- 0.014, P
      < 0.01) and DA (1.305 +/- 0.023, 1.237 +/- 0.024, P < 0.01) in middle and late
      stages in control group; the expression of DA following with the PIH degrees were
      decreased (1.378 +/- 0.029 vs 1.305 +/- 0.023 vs 1.237 +/- 0.024, P < 0.01); the
      expression of NE following the PIH degrees were increased (1.494 +/- 0.018 vs
      1.624 +/- 0.014 vs 1.917 +/- 0.044, P < 0.01). CONCLUSION: These findings
      suggested that NE and DA located in placental cytotrophoblast in early pregnancy
      and syncytiotrophoblast in middle and late stages and continuously distributed
      properly with the gestation. The level of NE increased with degrees PIH.

PMID- 11953081
TI  - [Changes of ATPase in fetal rat's cerebral mitochondria and endoplasmic reticulum
      subsequent intrauterus ischemia and hypoxia].
AB  - OBJECTIVE: To investigate the mechanism of intracellular calcium and other ions
      disturbance by measuring the activity of Ca(2+)-adenosine triphosphatase (Ca(2+)
      ATPase) and Na(+)-K(+) adenosine triphosphatase (Na(+)-K(+) ATPase). METHODS:
      Model of fetal rats ischemia and reperfusion was established. The duration of
      ischemia was 15, 30, 45 and 60mins respectively; after ischemia for 15 mins,
      reperfusion for 1, 4, 8, 15 and 24 hours. There were 7 - 11 fetal rats sacrificed
      at different time points respectively, 12 rats in sham for control. The
      mitochondria and endoplasmic reticulium (microsomia) were estracted and the
      activity of the enzyme was measured. RESULTS: In the ischemia group: with the
      development of ischemia, the activity of Ca(2+)-ATPase in mitochondria decreased
      gradually (P < 0.01), but there was no obvious changes in endoplasmic reticulum.
      The activity of Na(+)-K(+) ATPase in the two organelles decreased progressively
      (P < 0.01). While in the reperfusion group: during the 24 hours of reperfusion,
      the activity of Ca(2+)-ATPase in mitochondria decreased obviously (P < 0.01), but
      no obvious change in endoplasmic reticulum. Meanwhile Na(+)-K(+) ATPase in this
      two organelles increased to normal level after reperfusion, but 8 hours later, it
      decreased for the second time. CONCLUSION: The changes of Ca(2+)-ATPase in
      mitochondria play an important role in the overload of intracellular Ca(2+)
      during ischemia and reperfusion, but in endoplasmic reticulium it needs further
      investigation. Na(+)-K(+) ATPase in the two organelles may be related with their
      edema.

PMID- 11953082
TI  - [A study on ways of intrauterine infection of chlamydia trachomatis].
AB  - OBJECTIVE: To study the route of intrauterine infection of chlamydia trachomatis
      (CT). METHODS: Seven hundred and seventy-two cervical samples from in women and
      105 matched maternal-labom neonatal samples composed of cervical samples, cord
      blood, amniotic fluid, conjunctival and nasopharyngeal samples of neonate were
      detected by PCR-SSCP and DNA sequencing technique. RESULTS: CT were detected in
      87 of 772 (11.3%) cervical samples. In the 81 matched maternal-infant samples
      from pregnant women with cervical CT-positive, CT were not detected in all of the
      cord blood samples. In the 30 CT-positive neonatal samples, 26 were from cases of
      vaginal delivery and 4 from cases of caesarean section. Statistical analysis
      showed a significant difference between the groups of caesarean section and the
      vaginal delivery (P < 0.01). Four of 11 amniotic fluid samples with CT-positive
      were obtained during caesarean section in which 3 were without premature rupture
      of membranes (PROM), SSCP patients were same between maternal samples and matched
      neonatal samples. The sequences of amplified DNA fragments also showed the same
      results between maternal and match neonatal samples. No samples were found CT
      positive in 24 matched maternal-infant samples from cervical CT-negative women.
      CONCLUSIONS: An ascending transmission from cervix to amniotic cavity was the
      major route for CT intrauterine infection. Transplacental passage of chlamydial
      infection was not confirmed. Rates of vertical transmission were significantly
      lower in caesarean section group than that of vaginal delivery group with
      maternal cervical chlamydial positive.

PMID- 11953083
TI  - [Study of effects of leptin on cultured human luteinized granulosa cell
      function].
AB  - OBJECTIVE: To assess the effects of leptin on follicle-stimulating hormone (FSH)
      and insulin-like growth factor-I (IGF-I) induced production of estradiol (E(2))
      17beta and progesterone (P) in cultured human luteinized granulosa cell (GC).
      METHODS: Human luteinized GCs were obtained from pre-ovulatory follicles in an in
      vitro fertilization program, and were cultured for 24 hours in the presence of
      leptin (3.0 ng/ml) or FSH (1.0 ng/ml) or IGF-I (30.0 ng/ml) alone, leptin with
      FSH or IGF-I or both, and FSH with IGF-I. The conditioned media were aspirated
      for measuring E(2) and P content. Luteinized GC were also counted for cell number
      and detected the expression of the leptin receptor by reverse transcription
      polymerase chain reaction analysis. RESULTS: In cultured luteinized GC system,
      leptin or FSH or IGF-I alone did not affect the growth of cultured human
      luteinized GC. Leptin alone or in the presence of FSH had no effect on E(2)
      production. E(2) levels in culture media without leptin or FSH were (0.103 +/-
      0.036) pmol/1 000 cells, (0.323 +/- 0.042) pmol/1 000 cells respectively. When
      cultured with leptin alone or with leptin and FSH, E(2) levels were (0.120 +/-
      0.008) pmol/1 000 cells, (0.343 +/- 0.034) pmol/1 000 cells. Leptin significantly
      inhibited FSH + IGF-I or IGF-I induced E(2) production. E(2) levels decreased
      from (0.318 +/- 0.037) pmol/1 000 cells to (0.193 +/- 0.025) pmol/1 000 cells
      (IGF-I) (P < 0.05) and from (0.493 +/- 0.036) pmol/1 000 cells to (0.251 +/-
      0.033) pmol/1 000 cells (FSH + IGF-I) (P < 0.01). However, the production of P
      did not change. The leptin receptor expression was demonstrated in luteinized GC.
      CONCLUSIONS: Leptin may directly attenuate the IGF-I or IGF-I and FSH-stimulated
      E(2) synthesis in cultured human luteinized GC by the leptin receptor mechanism.

PMID- 11953084
TI  - [Investigation on development potential of blastomeres isolated from 4-cell human
      embryos].
AB  - OBJECTIVE: To investigate the development potential of blastomeres isolated from
      4-cell human embryos. METHODS: Human oocytes were collected after controlled
      ovarian hyperstimulation and fertilized in vitro. The zona pellucida of 4-cell
      stage embryos were removed and the embryos were separated to single blastomeres
      and cultured in vitro. The development and differentiation of the blastomeres
      were observed. RESULTS: 83 blastomeres were isolated from 20 4-cell and 2 3-cell
      human embryos. Of those, 35 developed to expanded blastocyst. CONCLUSION:
      Blastomeres isolated from the 4-cell human embryos have the competence to develop
      to expanded blastocyst.

PMID- 11953085
TI  - [Systematic evaluation of the new screen methods of cervical intraepithelial
      neoplasm].
AB  - OBJECTIVE: To evaluate new cytologic screening methods of papnet cytology
      computer technology (CCT) and thinprep pap test (TPT) on cervical intraepithelial
      neoplasm (CIN). METHODS: Three hundred and seventy four cases with abnormal
      cervical cytologic results received colposcopic examinations and multiple
      biopsies. The results of cytologic screening compared with the results of
      histologic-colposcopic diagnosis were analysed retrospectively. RESULTS: A total
      of 374 cases were diagnosed by cytology, 9.1% with inflammations, 43.3% with low
      grade squamous intraepithelial lesion (LSIL) and 20.3% with high grade squamous
      intraepithelial lesion (HSIL) and 1.9% suspected with squamous cell carcinoma.
      However, after examination by colposcopy and multiple biopsies, the situation was
      different. The percentage of cases with inflammation increased to 53.5%, cervical
      intraepithelial neoplasm I (CIN I) decreased to 17.9%, CIN II and CIN III and
      cervical carcinoma in situ (CIS) elevated to 25.4% and invasive squamous cell
      carcinoma increased to 3.2%. Among cases with atypical squamous cell of
      undetermined significance (ASCUS), 52.6% (50/95) were with inflammations or
      negative results, 47.4% (45/95) with CIN I or even greater. Among 374 cases, 188
      women were screened by CCT and 186 by TPT. When all cytological findings compared
      with the histologic-colposcopic results, respectively, the coincidence of TPT
      with histologic-colposcopic results was significantly higher than that of CCT (P
      < 0.01). The coincidence rate (79.7%) of screening cases with LSIL or
      inflammation was significantly higher than that (20.3%) of cases with HSIL or
      even greater (P < 0.01). But there was no difference between two methods. The
      incidence of human papillomaviral infection (HPV) infection at colposcopies was
      34.0%. The high incidences of HPV and CIN infection were found among women from
      20 to 30 years old and from 30 to 50 years old, respectively. CONCLUSIONS: Cases
      with abnormal cytologic findings should undergo colpscopic examination and
      multiple biopsies for further diagnosis. Only in this way, cases with CIN or HPV
      infection could not be misdiagnosed. Women ranged from 30 - 50 years old should
      receive cytologic screening or colposcopic examination regularly.

PMID- 11953086
TI  - [Clinical characteristics of clear cell carcinoma of the ovary].
AB  - OBJECTIVE: To study the clinical characteristics of clear cell carcinoma of the
      ovary. METHODS: Forty three patients with clear cell carcinoma of the ovary and
      51 patients with serous adenocarcinoma of the ovary who were admitted in Peking
      Union Medical College Hospital between 1984 to 2000 were analyzed
      retrospectively, and their chemosensitivities and the survival rates were
      compared. RESULTS: The percentage of early stage patients in the clear cell
      carcinoma of the ovary and the serous adenocarcinoma of the ovary was 14.4% and
      3.8% respectively, the difference was significant (P < 0.005). In the late stage
      patients who underwent satisfactory cytoreductive surgery, the chemo-resistant
      rate (88.9%) in the clear cell carcinoma of the ovary was significantly higher
      than that (57.1%) of the serous adenocarcinoma of the ovary (P < 0.02), the 1
      year survival rate (79.0%) in the clear cell carcinoma of the ovary was
      significantly lower than that (96.2%) of the serous adenocarcinoma of the ovary
      (P < 0.01). In the late stage patients who underwent unsatisfactory cytoreductive
      surgery, the chemo-resistant rate and the survival rate had no significant
      difference between the clear cell carcinoma of the ovary and the serous
      adenocarcinoma of the ovary (P > 0.05). CONCLUSIONS: There are more early stage
      patients with clear cell carcinoma of the ovary. We should conduct auxiliary
      therapy and close follow up to them after surgery. Clear cell carcinoma of the
      ovary is chemo-resistant to platinum-based chemotherapy and has poor prognosis.

PMID- 11953087
TI  - [Time-dependent and dose-dependent regulation of human progesterone receptor
      isoforms A and B in uterine endometrial carcinoma by human insulin-like growth
      factor-I].
AB  - OBJECTIVE: We study the regulation of human progesterone receptor isoforms A and
      B in uterine endometrial carcinoma cell line by different concentration of human
      insulin-like growth factor-I (IGF-I) for different time, to investigate the roles
      of IGF-I and progesterone receptor isoforms in uterine endometrial carcinoma.
      METHODS: The uterine endometrial adenocarcinoma cell line HEC-IB was cultured in
      vitro and the breast cancer cell line MCF-7 was used as control. Western blot was
      applied to examine the changes of the two isoforms by different concentration IGF
      I for different time. RESULTS: (1) In HEC-IB cell line, 10 ng/ml IGF-I made hPRB
      up-regulated in the first 24 h. But according to lager concentration and longer
      time, human progesterone receptor (hPR) B became down-regulated, which were
      significant at 20 ng/ml IGF-I for 72 h and 40 ng/ml IGF-I for 48 - 72 h. The
      change of hPRA was like hPRB. (2) In MCF-7 cell line, 10 ng/ml and 40 ng/ml IGF-I
      made hPRA and hPRB significantly up-regulated in 24, 48, 72 h. Twenty ng/ml IGF-I
      made hPRB up-regulated also in the first 24 h. But in 48 h and 72 h, down
      regulation of hPRB was detected. Twenty ng/ml IGF-I made hPRA down-regulated in
      24, 48, 72 h. CONCLUSIONS: (1) The regulation of IGF-I to hPR isoforms has cell
      type specific and dose-dependent and time-dependent. (2) In HEC-IB cell line, 10
      ng/ml IGF-I made hPRB significantly up-regulated in 24 h. But following exposure
      to IGF-I at larger concentration and longer time, hPRB became down-regulated. The
      change of hPRA is like hPRB.

PMID- 11953088
TI  - [Study on expression of cell cycle-related genes in subclonal cell lines of human
      cervical carcinoma].
AB  - OBJECTIVE: To explore the role of expression of cell cycle-related genes in
      cervical carcinoma cell lines. METHODS: A series of expression microarray
      analysis of two homologous cervical carcinoma subclonal cell lines were initiated
      by cDNA microarray which represent a set of 234 human cell cycle-related genes.
      RESULTS: In normal medium, the percent of G(1) phase in CS03 cells was higher
      than in CS07 cells dramatically, but the percent of S phase in CS07 cells was
      more than in CS03 cells. After cultured 48 h in serum-free medium, the percent of
      apoptosis cells (sub-G(1) phase) in CS03 cells was higher than in CS07 cells
      significantly and increased with time. By applying this cDNA microarray, we
      identified 3 differentially expressed genes in two homologous cell lines, which
      were BN51, hsp90 and Mcl-1 genes, further identified 3 upregulated genes in CS07
      cell line, the ratio of Cy5/Cy3 was 0.480, 0.479 and 0.490 respectively.
      CONCLUSION: Differential expression of BN51, hsp90 and Mcl-1 genes is associated
      to various growth patterns of human cervical carcinoma cells.

PMID- 11953089
TI  - [Report on fourth national epidemiological sampling survey of tuberculosis].
AB  - OBJECTIVE: To investigate the epidemiological trend of tuberculosis, to evaluate
      the efficacy of control measures and to provide scientific basis for making
      National Tuberculosis Control Programme 2001 approximately 2010. METHODS:
      Tuberculin testing was carried out among 0 approximately 14 years old children;
      fluroscopy was carried out for >/= 15 years old population and children with >/=
      10 mm reaction of tuberculin testing; chest X-ray film, sputum smear and culture
      were done for the patients of fluroscopy abnormal and suspects of tuberculosis
      symptom (persistent cough for 3 weeks or more); drug sensitivity test was done
      for the patients with culture positive; a retrospective study of tuberculosis
      mortality in 1999 was conducted at all investigation points; social economic
      study was done for the active pulmonary tuberculosis cases; the survey of
      tuberculosis infection rate for all population was carried out in 59
      investigation points. RESULTS: The population actually examined in this survey
      numbered 365 097. The examination rate was more than 95%. The prevalence of
      active pulmonary tuberculosis was 367/100 000, the prevalence of smear positive
      pulmonary tuberculosis was 122/100 000 and the prevalence of bacteriological
      positive pulmonary tuberculosis was 160/100 000. In comparison with 1979, the
      annual reduction rates were 4.5% for the standardized prevalence of active
      pulmonary tuberculosis and 3.8% for the standardized prevalence of smear positive
      pulmonary tuberculosis. In comparison with 1990, the annual reduction rates were
      5.4% and 3.2%, respectively. The smear positive prevalence standardized showed a
      44.4% decrease in the regions of implementing project of Health V but only 12.3%
      decrease in the regions without the project. The prevalence in the west region
      was higher than national average prevalence. CONCLUSIONS: The epidemic of
      tuberculosis is still serious and prevalence decrease was slow. The governments
      at different levels must pay more attention to tuberculosis control programme,
      increase budget, implement DOTS strategy.

PMID- 11953090
TI  - [Report on fourth epidemiological survey for tuberculosis in Heilongjiang
      province].
AB  - OBJECTIVE: To investigate the epidemiological trend of tuberculosis, to evaluate
      the efficacy of control measures and to provide scientific evidence for
      provincial 2001 approximately 2010 tuberculosis control programme. METHODS:
      Tuberculin testing was carried out and BCG scar was examined among 0
      approximately 14 years old children; fluroscopy was carried out for >/= 15 years
      old population and children of tuberculin testing positive; chest X-ray film,
      sputum smear and culture, drug sensitivity test were done for the patients of
      fluroscopy abnormal; the survey of tuberculosis infection rate for all population
      was carried out in 2 investigation points; a retrospective study of tuberculosis
      mortality was conducted at all investigation points; social economic study was
      done for the active pulmonary tuberculosis cases. RESULTS: The overall
      examination rate was more than 95%. The prevalence of active pulmonary
      tuberculosis was 512/100 000, the prevalence of smear positive pulmonary
      tuberculosis was 121/100 000 and the prevalence of bacteriological positive
      pulmonary tuberculosis was 146/100 000. In comparison with 1979, the annual
      reduction rates were 3.2% for the prevalence of active pulmonary tuberculosis and
      2.0% for the prevalence of smear positive pulmonary tuberculosis. In comparison
      with 1990, the annual reduction rates were 1.49% and 0, respectively. The
      prevalence increased slightly in city and decreased slowly in countryside.
      CONCLUSIONS: The smear positive prevalence has not decreased since 1990. The
      governments at different levels must pay more attention to tuberculosis control
      programme, increase the budget, strengthen law management, implement DOTS
      strategy.

PMID- 11953091
TI  - [Study on epidemic trend and control policy of tuberculosis in Sichuan province].
AB  - OBJECTIVE: To evaluate efficacy of tuberculosis control policy and provide
      scientific evidence for drawing up tuberculosis control program. METHODS: Data of
      the epidemiological survey for tuberculosis in Sichuan in 2000 were analyzed and
      part of the results were compared with that before. RESULTS: The prevalence of
      active pulmonary tuberculosis, the bacteriological positive prevalence and smear
      positive prevalence of pulmonary tuberculosis in 2000 were 544/100 000, 250/100
      000 and 144/100 000, respectively, decreased by 41.8%, 30.0% and 35.0%
      respectively in comparison with 1990, and the annual reduction rates were 5.3%,
      3.5% and 4.2% respectively during the past 10 years. The mortality of
      tuberculosis and pulmonary tuberculosis was 24/100 000 and 22/100 000,
      respectively, decreased by 20.0% and 12.0% respectively in comparison with 1990.
      The prevalence of tuberculosis in minority area and mountainous area were higher
      than that in city, countryside and hills. 71% of infectious patients were newly
      detected, 33.3% of which were re-treatment cases. The economic status was found
      the key factor affecting the implementation of tuberculosis control. CONCLUSIONS:
      The modern tuberculosis control strategy, which mainly targeted infectious
      patients and advocated DOTS policy, is the guarantee of sustainable development
      of tuberculosis control, though the prevalence of pulmonary tuberculosis
      decreased slowly in Sichuan during the past 10 years.

PMID- 11953092
TI  - [Epidemic trends of pulmonary tuberculosis and case finding in Henan province].
AB  - OBJECTIVE: Based on the data of the 4th national epidemiological survey in 2000
      in Henan province, to obtain the trends of epidemic situation of pulmonary
      tuberculosis, and to analyze the methods of case finding. METHODS: The detection
      methods such as X-ray, sputum examination and PPD were used to diagnose active
      pulmonary tuberculosis from sampling population. RESULTS: The prevalence of
      active pulmonary tuberculosis is 497 per 100 000 population, the prevalence of
      smear positive pulmonary tuberculosis is 132 per 100 000 population. Comparing to
      the third survey in 1990, the reduction rate of prevalence of smear positive
      pulmonary tuberculosis is 6.15%, the annual reduction rate only 0.63%, indicating
      the prevalence declined very slowly in ten years. The rate of case finding
      increased by 6.6% after sputum specimens increased from 2 to 3. CONCLUSIONS: The
      epidemic status of pulmonary tuberculosis in Henan is still serious, and the case
      finding of tuberculosis should be strengthened. Increasing the times of sputum
      examination from 2 to 3 can increase the rate of case finding.

PMID- 11953093
TI  - [IS6110-restriction fragment length polymorphism based DNA fingerprinting in
      molecular epidemiology of tuberculosis].
AB  - OBJECTIVE: To identify the IS6110-restriction fragment length polymorphism (RFLP)
      DNA fingerprinting patterns of some clinical isolates of Mycobacterium
      tuberculosis (MTB) isolated from Ningxia, Beijing and Shanghai in recent years,
      and to observe their epidemiological characteristics. METHODS: Chromosomal DNA of
      MTB was digested with endonuclease PvuII, then electrophoresed on agarose gel
      plate and transferred capillarilly to a nylon filter and hybridized with 245 bp
      fragment of IS6110 which labeled using random primer fluorescein labeling kit.
      The RFLP patterns of Southern hybridization were inspected autofluorographically
      and the chromosomal DNAs of MTB were thereby typed. RESULTS: Most of 103 isolates
      of MTB shared 8 approximately 21 copies. Some of them were clustered. Strains
      isolated from Ningxia and Beijing had similar DNA fingerprinting patterns. One
      zero copy strain and one single copy strain were found among isolates from
      Shanghai. CONCLUSIONS: IS6110-RFLP based typing is feasible for MTB molecular
      epidemiological study in China. Most of isolates of MTB show analyzable patterns.
      Isolates of MTB from Ningxia and Beijing have close genomic relation.

PMID- 11953094
TI  - [Experimental study on prevention of diabetes complicated with tuberculosis by
      Mycobacterium vaccae].
AB  - OBJECTIVE: To study if Mycobacterium vaccae has any effect in prevention of rats
      with diabetes from tuberculosis. METHODS: Wistar rats with diabetes which were
      produced by injection of streptozotocin one week before were divided into four
      groups. Mycobacterium vaccae was injected into Wistar rats with diabetes and one
      month later H(37)R(v) was injected intravenously. The rats were sacrificed six
      weeks later to observe pathomorphologic changes in lung tissues. Indexes for
      evaluation included quantitative culture of Mycobacterium tuberculosis of lung
      tissue, tubercular lesion, count of Mycobacterium tuberculosis in alveolar
      macrophages and histopathological changes. RESULTS: Pathological change index of
      tubercular lesion, quantitative culture of Mycobacterium tuberculosis in lung
      tissue, count of Mycobacterium tuberculosis in alveolar macrophages were 2.5 +/-
      0.7, (4.1 +/- 0.6) x 10(4) cfu, 2.6 +/- 0.9 respectively in group injected with
      Mycobacterium vaccae, while 3.3 +/- 0.5, (9.9 +/- 1.0) x 10(4) cfu, 7.2 +/- 0.7
      respectively in the control group. Statistically significant differences were
      found between the two groups (P < 0.05, < 0.01, < 0.01 respectively). The
      histopathological changes of lung tissue in group of diabetes complicated with
      tuberculosis revealed that the lesions were predominant with necrosis, while in
      group injected with Mycobacterium vaccae, the lesions showed proliferation
      mainly. This indicated that Mycobacterium vaccae could decrease the damage to the
      lung tissue of the rat with diabetes by tubercle bacilli. CONCLUSION:
      Mycobacterium vaccae might play a role in prevention of rat with diabetes from
      tuberculosis.

PMID- 11953095
TI  - [Epidemiological survey on bronchial asthma in Henan province].
AB  - OBJECTIVE: To survey asthma prevalence, correlation factors for prevention,
      treatment, and for policy decision of asthma control. METHODS: Done with TB
      epidemiological survey synchronously, sampling by stratified-cluster-random
      method. 43 points were selected and distributed in all 18 prefectures in Henan
      province. Sampling population was 75 134, and 65 033 (97.0%) were investigated
      actually. RESULTS: In this survey, 682 asthma patients were found. The total
      prevalence rate was 1.05%, the rate for children was 1.71%, and that for adult
      was 0.82%; the rates for male and female were 1.16%, 0.94% respectively. The
      ratio of male to female was 1.23:1. When asthmatic chronic bronchitis cases were
      regarded as asthma cases and included in total asthma cases, the overall
      prevalence rate of asthma would increase up to 1.73%, raised by 65%. The higher
      prevalence were in 0 approximately 3 years old age group (4.48%) and >/= 65 years
      old age group (1.43%), the lowest prevalence was in 15 approximately 24 years old
      age group (0.36%). For 90% of asthmatic children, the initiative age of asthma
      was before 7 years old, and for 1/3 adult patient, it was in childhood. The
      prevalence of asthma in rural area was higher than that of urban area. Cold air,
      common cold, stimulation of smoking and cooking, and room dust were the 4 main
      inducing factors. Seasonal attack of asthma accounted for 67.2%, and that in
      winter and spring was 65.4%. 60.6% of asthma cases showed history of allergic
      diseases including allergic rhinitis, dermatitis, and drug allergy; 34.3% asthma
      family history. CONCLUSIONS: The rate of prevalence and inducing factors of
      asthma in Henan province were gained in this survey. The results may basically
      reflect the present status and be provided for asthma control as reference.
      According to the prevalence, asthma cases would be up to 0.98 approximately 1.6
      million in whole Henan province and more attention should be paid to this
      situation.

PMID- 11953096
TI  - [Eotaxin in induced sputum in patients with asthma and chronic bronchitis:
      relationship with airway inflammation].
AB  - OBJECTIVE: Investigate the roles of eotaxin (chemotactic factor of eosinophils)
      in pathogenesis of eosinophilic airway inflammation and airflow obstruction.
      METHODS: 33 patients in exacerbations with chronic bronchitis (CB group), chronic
      asthmatic bronchitis (CAB group) and bronchial asthma (BA group) (11 cases
      respectively) and 7 healthy volunteers as controls (C group) have participated in
      lung function test and sputum induction. The concentration of eotaxin in
      supernatant was measured by sandwich enzyme linked immunosorbent assay (ELISA).
      RESULTS: The differences of the eosinophil (EOS)/leukocyte (Leu)% in CAB group
      [(23.4 +/- 5.8)%], BA group [(20.7 +/- 3.1)%] and in CB group [(11.6 +/- 2.6)%],
      C group [(1.2 +/- 0.3)%] are significant (P < 0.001), and the differences of the
      level of eotaxin in CAB group [(0.290 +/- 0.170) g/L], BA group [(0.240 +/-
      0.140) g/L] and in CB group [(0.120 +/- 0.020) g/L], C group [(0.030 +/- 0.050)
      g/L] are also significant [CAB group-CB group (P = 0.007); CAB group-C group (P <
      0.001); BA group-CB group (P = 0.018); BA group-C group (P = 0.001)], but the
      differences of those in BA group and in CAB group are not significant (P = 0.196,
      0.490). The EOS/Leu % is significantly inversely correlated with the percentage
      of the first second forced expiratory volume/predicted value (FEV(1)%) in CAB
      group (r = -0.921, P < 0.001). The EOS/Leu % and the level of eotaxin are
      significantly inversely correlated with FEV(1)% respectively in BA group (r = 
      0.663, -0.643, P = 0.026, 0.033). The level of eotaxin in induced sputum is
      significantly positively correlated with the EOS/Leu % in CAB group (r = 0.658, P
      = 0.028) and BA group (r = 0.634, P = 0.036), but it is not correlated with any
      of Neu/Leu %, macrophage (Macro)/Leu % or lymphocyte (Lym)/Leu % in any group (P
      > 0.05). CONCLUSION: Eotaxin possibly particulates in eosinophilic airway
      inflammation in patients with BA and CAB by selective chemotactic activity on
      eosinophil.

PMID- 11953097
TI  - [Changes of antioxidative capacity and endothelial function before and after
      treatment among patients with high altitude pulmonary edema].
AB  - OBJECTIVE: To investigate the changes of antioxidative capacity and endothelial
      function among patients with high altitude pulmonary edema (HAPE). METHODS: The
      serum levels of SOD, MDA, GSH, NO, NOS and ET-1 were measured before and after
      treatment among 34 cases of patients with HAPE, and 20 local healthy volunteers
      served as control. RESULTS: The serum levels of SOD, GSH, NO and NOS were lower
      in patient-group before treatment than after treatment and those in control-group
      significantly (P < 0.01), while the concentration of MDA and ET-1 were higher in
      patient-group before treatment than after treatment and those in the control
      group significantly (P < 0.01). The serum levels of SOD, MDA, GSH, NO, NOS and ET
      1 were not different between patient-group after treatment and the control-group
      (P > 0.05). CONCLUSION: The results indicated that changes of SOD, MDA, GSH, NO,
      NOS and ET-1 may participate in the course of HAPE.

PMID- 11953099
TI  - [The change of alveolar fluid clearance in acute lung injury rat].
AB  - OBJECTIVE: To establish the animal model of lung injury caused by hydrochloric
      acid in rats, measure the alveolar fluid clearance (AFC) in different acidic
      condition. METHODS: 32 rats were randomly divided into 4 groups which were
      control group (pH = 7.4) and HCl groups (pH = 7.0, 4.5, 2.5). The animals were
      anesthetized and ventilated for 1 hour. Blood gas analysis was performed, then
      the permeability of lung epithelial barrier and AFC were measured. RESULTS: The
      permeability of lung epithelial barrier, PaO(2) and AFC of pH 7.0 group were
      similar to control group (P > 0.05), but declined in pH 4.5 and 2.5 groups (P <
      0.05). CONCLUSIONS: The alveolar epithelium and the alveolar epithelial barrier
      are resistant to the injurious effects of acid, but high concentration acid can
      induce damage.

PMID- 11953098
TI  - [The influence of nasal continual positive airway pressure on some vasoactive
      substances in patients with obstructive sleep apnea syndrome].
AB  - OBJECTIVE: To investigate the influence of nasal continual positive airway
      pressure (nCPAP) on the plasma levels of thromboxane B(2) (TXB(2)), renin,
      angiotensin II (AT-II), endothelin 1 (ET-1), cyclic AMP (cAMP) and cyclic GMP
      (cGMP) and evaluate their clinical significance. METHODS: 20 patients with OSAS
      without cardiovascular complications and 20 nromal controls were enrolled in the
      study, who were monitored with PSG, and then treated with nCPAP during the second
      night. All the plasma parameters were measured after PSG monitoring and nCPAP
      management with radio-immunoassay. RESULTS: Before nCPAP, plasma levels of
      TXB(2), renin, and AT-II were higher in patients with OSAS than those in control
      (P < 0.05); Meanwhile, the plasma levels of ET-1, cAMP, and cAMP/cGMP were
      significantly higher in patients group than those in control (P < 0.01).
      CONCLUSIONS: Patients with severe OSAS may have disturbances in neuro-regulation
      and changes in plasma level of TXB(2), renin, AT-II and ET-1, which indicates
      that the vasoactive substance might be related to the hypoxemia and disturbance
      in neuro-regulations, and might play an important role in the development of
      hypertension and other cardiovascular disorders. nCPAP therapy can correct the
      abnormalities of some vasoactive substances.

PMID- 11953100
TI  - [A nationwide questionnaire survey on clinical application of pulmonary function
      testing in China].
AB  - OBJECTIVE: Assessment of the clinical application of pulmonary function testing
      (PFT) in China. METHOD: A questionnaire survey was performed in 212 hospitals
      covering 29 provinces of China. RESULTS: The response rate was 81.6%. PFT had
      been conducted in 91.9% of the responders, of which 69.2% were from large
      (provincial or municipal) hospitals. PFT was introduced to many hospitals in late
      1970's, and has been used widely in early 1990's. Only 12.4% of the instruments
      being used was made domesticly. The frequencies of average PFT per month and per
      bed were low and a large variation existed among hospitals. PFT had been used
      more in the departments of internal medicine and surgery, but less in pediatrics,
      gynecology, and ENT. Spirometric measurement was the most common testing
      (performed 100%), followed by bronchial dilation test (74.2%) and bronchial
      provocation test (65.4%). Lung volume, diffusion capacity and airway resistance
      measurement had been conducted in 60.0%, 58.2%, and 42.7%, of the large
      hospitals, respectively. Exercise test was conducted in only 16.4% of the large
      hospitals. The reference norms were stated in only 21.4% of the hospitals.
      Prediction equations available for children were stated in only 16.9% hospitals
      where PFT were performed in children. Prediction equations derived from mainland
      Chinese were used in only 16.3% lung function laboratories. CONCLUSIONS: The
      clinical application of PFT in China is not popular and varies from hospital to
      hospital. It is imperative to develop domestic lung function instruments as well
      as lung function norms for Chinese.

PMID- 11953101
TI  - [The effect of bradykinin B(2) receptor antagonist on cough reactivity in a
      sensitized guinea pig model].
AB  - OBJECTIVE: To investigate the effect of bradykinin B(2) receptor antagonist
      FR173657 on cough response in guinea pigs sensitized and challenged with
      ovalbumin. METHODS: 40 normal and 40 sensitized guinea pigs were challenged with
      the aerosol of ovalbumin. 24 hours later, 10 animals from the normal group and 10
      from the sensitized group were intraperitoneally injected either with saline or
      with 0.03 mg/kg, 0.3 mg/kg and 3 mg/kg of FR173657 respectively, and then cough
      response to inhaled capsaicin was measured. Specific airway resistance was
      recorded with a noninvasive technique only in normal, sensitized and FR173657
      (0.3 mg/kg)-treated sensitized guinea pigs. RESULTS: FR173657 did not influence
      cough response and airway resistance in normal guinea pigs. Compared with normal
      animals, sensitized guinea pigs presented an increased cough frequency and
      specific airway resistance [(21.7 +/- 3.0) times/3 min vs (8.3 +/- 1.4) times/3
      min, (9.4 +/- 0.5) cm H(2)O/s vs (7.9 +/- 0.9) cm H(2)O/s], (P < 0.05) after
      inhalation of 10(-4) mol/L capsaicin. The cough frequency and specific airway
      resistance were decreased to [(12.2 +/- 1.3) times/1 min and (7.5 +/- 0.9) cm
      H(2)O/s] after administration of 0.3 mg/kg of FR173657 (P < 0.05). CONCLUSIONS:
      Bradykinin B(2) receptor antagonist inhibited increased cough response and airway
      resistance in guinea pigs sensitized and challenged with ovalbumin. Bradykinin
      may be an important mediator in cough associated with eosinophilic airway
      inflammation.

PMID- 11953102
TI  - [Restricted usage of repertoire of T-cell receptor V beta in Chinese asthmatics].
AB  - OBJECTIVE: To investigate the association of restricted usage of repertoire of T
      cell receptor V beta (TCR V beta) with asthma. METHODS: In 36 Chinese asthmatics,
      peripheral blood TCR V beta was studied by means of fluorescein-labeled RT-PCR as
      well as genescan and genotype software analysis. The clonality of the predominant
      usage T cell receptors was analyzed by denaturing gel electrophoresis and single
      strand conformation polymorphism (SSCP) by using genescan analysis (with 377 ABI
      DNA sequencer). RESULTS: The number of cases predominantly using TCRV beta 8 gene
      families in asthmatics and those allergy to house dust mite (HDM) was
      significantly higher than that of normal controls (P = 0.0230, 0.0147), and so
      the TCR V beta 5.1 gene family for asthmatics allergic to HDM (P = 0.0186). It is
      remarkable-that only two cases in 36 asthmatics were allergic to ragweed and both
      of them predominantly used TCR V beta 1 gene families. The TCR V beta gene
      families predominantly used in asthmatics showed polyclonal expression in all
      normal controls and most asthmatics, but 5 asthmatics showed oligoclonal
      expression of TCR V beta 8 gene families. CONCLUSIONS: TCRV beta 8 and TCR V beta
      5.1 gene families may be associated with allergy to HDM in asthmatics. TCR V beta
      gene families in asthmatic peripheral blood showed oligoclonal expression
      tendency.

PMID- 11953103
TI  - [A clinicopathologic study of nonspecific interstitial pneumonia].
AB  - OBJECTIVE: To investigate the clinicopathologic features of nonspecific
      interstitial pneumonia (NSIP). METHODS: The clinical and pathological data of 8
      cases with NSIP confirmed by open or video-assisted thoracoscopic lung biopsy
      were reviewed retrospectively. RESULTS: NSIP occurred more in female (male:female
      1:3, 2/6), and the patients' average age was 48 years. The clinical manifestation
      was progressive dyspnea, cough and sputum, crackles over both lungs and
      restrictive ventilating abnormalities. Reticular changes and patchy ground-glass
      attenuation in lower lung fields were the main findings on high resolution
      computed tomography. The pathological characteristic was uniform interstitial
      inflammation and fibrosis. Three cases showed fibroblast foci, was BOOP like
      changes in 4 and honeycombing in 1 case. of the 8 patients, 6 had cellular and
      fibrosing patterns; 2 had fibrosing patterns only; the former showed better
      response to glucocorticoid therapy than the latter. CONCLUSIONS: The histologic
      patterns of NSIP correlated closely with the therapeutic effect of
      glucocorticoids. It is difficult to differentiate pathologically the fibrosing
      pattern of NSIP from usual interstitial pneumonia, therefore clinical data are
      indispensable in the diagnosis.

PMID- 11953104
TI  - [Safety analysis of CT-guided core needle lung biopsy].
AB  - OBJECTIVE: To study the safety of CT-guided core needle lung biopsy. METHODS: 290
      cases of core-needle lung biopsy dated from April 1996 to April 2001 were
      studied. Complications of core-needle lung biopsy and their incidence and
      relationship with puncture site, diameter of the needle and depth of the target
      lesion were retrospectively analyzed. RESULTS: Of the 290 cases, 69 cases of mild
      pneumothorax (23.8%), 11 (3.8%) medium pneumothorax, 46 (15.9%) pulmonary
      bleeding, 2 (0.7%)hemoptysis, 2 (0.7%) bleeding in the thoracic cavity were
      identified. Drainage was done in 3 cases of pneumothorax and emergency operation
      was needed in 1 case of thoracic cavity bleeding. The rest of the complications
      resolved spontaneously after several days of bed rest. CONCLUSIONS: CT-guided
      biopsy is a reliable and relatively safe aggressive diagnostic method to get
      hologic diagnosis. Pneumothorax and pulmonary bleeding are the most common
      complications, which correlated with the depth of the target lesions in the lung
      and have no correlation with the lesion location.

PMID- 11953105
TI  - [Correlation of angiogenesis with expression of vascular endothelial growth
      factor and its receptors in lung carcinoma].
AB  - OBJECTIVE: In order to search new therapeutic strategies, study the relationship
      between angiogenesis and vascular endothelial growth factor and its two receptors
      in lung carcinoma. METHODS: The study consisted of 49 patients with lung
      carcinoma treated with curative surgery. Immunohistochemistry on paraffin
      sections was performed with anti-human factor VIII antibody to study the
      microvascular density (MVD), and with antibodies to VEGF, Flt1, and KDR to
      investigate the expression of these three proteins in different cellular
      compartments. The survival time was compared between low MVD and high MVD groups
      by the Kaplan-Meier method. RESULTS: (1) Expression of VEGF and its two receptors
      in tumor cells, stromal fibroblasts and endothelial cells was demonstrated. (2)
      There was no significant difference between low MVD and high MVD groups in the
      clinical data, including TNM stage, clinical phase, pathologic type, and tumor
      cell differentiation (P > 0.05). Survival analysis showed that the high MVD group
      was associated with a high risk of death. (3) There was no significant difference
      between low MVD and high MVD groups in VEGF expression in tumor cells, but in
      endothelial cells both Flt1 and KDR were correlated with high microvessel count.
      (4) The high expression of VEGF in tumor cells was correlated with that in
      stromal fibroblasts. The level of expression in both cells was consistent. (5) In
      both tumor cells and endothelial cells, high co-expression of VEGF and KDR was
      consistent, but that of VEGF and Flt1 showed inconsistency. CONCLUSIONS: (1) Not
      or rarely affected by clinical factors, MVD is a good and independent prognostic
      factor for patients with lung carcinoma. (2) The angiogenesis is induced not only
      by VEGF itself, but via VEGF receptors too. VEGF and its receptors thus appear to
      be new therapeutic targets for lung carcinoma. (3) VEGF appears to be produced by
      both tumor cells and stromal fibroblasts. (4) The result suggests that tumor
      expansion and angiogenesis are mainly induced by an autocrine pathway and a
      paracrine loop of VEGF via KDR.

PMID- 11953106
TI  - [Study of the function of leukocyte adhesion molecules in chronic respiratory
      diseases].
AB  - OBJECTIVE: To study the function of leukocyte adhesion molecules in the
      pathogenesis of Chronic Obstructive Pulmonary Diseases (COPD) and cor pulmonale,
      and to evaluate the effect of anti-leukocyte-adhesion therapy for cor pulmonale.
      METHODS: The positive expression rates of CD(11a), CD(11b), CD(18), CD(54) in
      peripheral blood were quantitatively analyzed by flow cytometry using monoclonal
      antibodies in 42 cases of COPD (stable stage), 41 cases of cor pulmonale (stable
      stage), 24 healthy controls as well as 20 cases of cor pulmonale who had taken
      huobahua. RESULTS: The expression rates of CD(11a), CD(11b), CD(18), CD(54) in
      monocytes and CD(11a) in lymphocytes from the COPD group were much higher than
      those in the control group (P < 0.05). CD(11a), CD(11b), CD(18), CD(54) in
      neutrophils and CD(11a), CD(18), CD(54) in monocytes, and CD(18) in lymphocytes
      in the cor pulmonale group were significantly stronger than those in the control
      group (P < 0.05); whereas the positive expression of CDs was greatly reduced in
      the cor pulmonale patients who had taken huobahua (P < 0.05). No differences were
      found in other groups. CONCLUSIONS: Upregulation of CD(11a)/CD(18),
      CD(11b)/CD(18), CD(54) in monocytes, CD(11a)/CD(18), CD(11b)/CD(18), CD(54) in
      neutrophils and CD(11a)/CD(18), CD(54) in monocytes in cor pulmonale may promote
      adhesion of leukocytes with endothelial cells, which may play an important role
      in the pathogenic process. Huobahua may prevent the development of cor pulmonale
      by down regulating the expression of CDs.

PMID- 11953107
TI  - [Immunodeficiency tuberculosis: report on 5 autopsy cases].
AB  - OBJECTIVE: To improve the awareness of immunodeficiency tuberculosis. METHODS: 5
      autopsy cases of immunodeficiency tuberculosis from 1972 to 2000 in two hospitals
      were reviewed. RESULTS: The 5 cases were found to have hypoplasia of or damage in
      the thymus, among them 3 had massive tuberculous lymphadenitis lesions.
      Multiorgan lesions were found more in both lungs than in other organs,
      accompanied by lymphatic spread and blood dissemination. The microscopic feature
      was atypical tuberculosis with great amounts of Mycobacterium tuberculosis.
      CONCLUSIONS: Hypoplasia of or damage in the thymus and peripheral lymphoid tissue
      caused deficiency in the immune response, which resulted in the death of the
      patients with generalised tuberculosis by blood dissemination and lymphatic
      spread. The underlying mechanism of immunodeficiency tuberculosis is largely
      unknown, and further research is needed.

PMID- 11953108
TI  - [Change of immunosuppressive acidic protein in sera of patients with pulmonary
      tuberculosis and its clinical significance].
AB  - OBJECTIVE: To investigate the change of immunosuppressive acidic protein (IAP) in
      sera of patients with pulmonary tuberculosis (TB) and its clinical value. METHOD:
      IAP in sera of 336 patients suffering from pulmonary TB and controls was detected
      by agar diffusion assay. RESULTS: In pulmonary TB, healthy controls and non-TB
      respiratory diseases, the level of IAP was (797 +/- 168) mg/L, (367 +/- 71) mg/L
      and (404 +/- 75) mg/L, respectively. If > 500 mg/L was regarded as positive
      threshold, the positive rates in the above groups were 96.7%, 9.2% and 9.6%,
      respectively. IAP positive rates in cases of primary, disseminated, infiltrative,
      chronic fibro-cavernous pulmonary TB and tuberculous pleuritis were 100, 0%,
      100.0%, 96.0%, 98.6% and 96.9%, respectively. IAP was significantly higher in
      progressive pulmonary TB than in stable pulmonary TB, and was decreased when
      patients' condition improved after treatment. CONCLUSION: Detection of IAP in
      sera of patients with pulmonary TB can reflect patients' immunosuppression status
      and the severity of the disease, and may be useful in assessing treatment effect
      and evaluating prognosis.

PMID- 11953109
TI  - [Anterior vertebrectomy and plating for spinal tuberculosis].
AB  - OBJECTIVE: To study the effect of anterior vertebrectomy, bone grafting and
      plating in the treatment of spinal tuberculosis. METHODS: Between February 1998
      and August 2000, 12 patients with spinal tuberculosis were operated with anterior
      vertebrectomy, bone grafting and plating. Evaluation including bone fusion rate,
      correction of deformity and status of spinal lesion was carried out. RESULTS: In
      an average of ten months, spinal tuberculosis was completely cured and solid bone
      fusion had taken place in all 12 patients. The time for bone fusion averaged 5.8
      months and the average angle of correction of kyphosis was 16 degrees.
      CONCLUSIONS: Anterior plating following vertebrectomy and bone grafting offers a
      complete removal of lesion and decompression of the spinal canal as well as
      reconstruction of spinal stability. Early rehabilitation and an increased
      curative rate can be expected through this procedure.

PMID- 11953110
TI  - [Effect of nutritional state on cardiopulmonary exercise performance in patients
      with chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To explore the effect of nutritional state on cardiopulmonary exercise
      performance of chronic obstructive pulmonary disease (COPD) patients. METHODS: 43
      COPD patients and 20 healthy controls performed incremental cardiopulmonary
      exercise testing with cycle ergometer. Nutritional assessment and routine lung
      function studies were performed in all subjects before testing. RESULTS: (1)
      Compared with the normally nourished COPD group, the malnourished group showed
      greater reduction in Wmax, VO(2)max, O(2)pulsemax, and AT (P < 0.05), whereas
      VO(2)/W/V(E) and DImax were higher in the malnourished group (P < 0.05). (2) IBW%
      was positively correlated with VO(2)max, Wmax, O(2)pulsemax, AT (r = 0.696,
      0.432, 0.717, 0.822, P < 0.01), and negatively correlated with DImax and
      VO(2)/W/V(E) (r = -0.450, -0.640, P < 0.01) in COPD patients. CONCLUSION:
      Malnutrition adversely affected muscle aerobic capacity and exercise tolerance in
      COPD patients.

PMID- 11953111
TI  - [CT pulmonary functional imaging in emphysema: a correlative study of CT
      technique and pulmonary function test].
AB  - OBJECTIVE: To compare the effectiveness of high resolution CT, CT pulmonary
      functional imaging, and pulmonary function test (PFT) in the quantitative
      evaluation of emphysema and obstructive pulmonary disease. METHODS: The study
      included 37 patients with obstructive ventilatory defect and 20 normal controls.
      CT and pulmonary function test were performed in all subjects in one week.
      Correlation between and differences among HRCT visual scoring, parameters of CT
      pulmonary functional imaging and the result of pulmonary function test were
      compared. RESULTS: (1) Emphysema was detected by CT in 23 of the 37 patients with
      obstructive ventilatory defect. (2) HRCT visual scoring was correlated only with
      D(L)CO% (r = -0.731, P < 0.001) among other pulmonary function parameters. (3)
      HRCT visual scoring in patients with enrphysema was correlated with pixel indices
      (PI) at full inspiration and expiration. Visual scoring showed the best
      correlation with PI(-910in) (r = 0.506, P < 0.001) and PI(-910ex) (r = 0.610, P <
      0.001). (4) The grading of pulmonary function based on PI(-910in) and PI(-910ex)
      showed no difference from the grading by pulmonary function tests (chi(2) =
      0.527, P = 0.913; chi(2) = 3.645, P = 0.302). The grading of emphysema based on
      PI(-910in) accorded with the grading by pulmonary function tests (chi(2) = 2.59,
      P = 0.459). CONCLUSIONS: HRCT is more sensitive than conventional CT in
      diagnosing emphysema. However, in terms of slice thickness and radiation dose, it
      cannot be used in the evaluation of both lungs. CT functional imaging is easily
      performed, and the results are objective and correlated with the result of HRCT
      visual scoring and PFTs. It may be, therefore, more useful in diagnosing early
      emphysema and evaluating lung function.

PMID- 11953112
TI  - [The primary diagnostic significance of the epworth sleepiness scale in patients
      with obstructive sleep apnea syndrome].
AB  - OBJECTIVE: To evaluate the diagnostic usefulness of epworth sleepiness scale
      (ESS) in patients with OSAS. METHODS: The questionnaire of the epworth sleepiness
      scale was used to evaluate 189 patients with OSAS and 42 patients with snoring.
      The results were compared to those of polysomnography. RESULTS: Significant
      differences in ESS-SP, AHI and sleep structure were found between patients with
      OSAS and patients with scoring. A significant correlation was found between ESS
      SP score and AHI (r = 0.44, P < 0.01). The patients with OSAS had significantly
      higher scores than those without OSAS. The specificity of this method was 83%
      (snoring), 90% (mild OSAS), 79% (moderate OSAS) and 82% (severe OSAS).
      CONCLUSION: ESS-SP is consistent with clinical diagnosis and could be used as a
      primary diagnostic method in patients with OSAS, especially in primary-care
      hospitals.

PMID- 11953113
TI  - [The observation of local immune response in the lungs from antigen-sensitized
      and challenged mice].
AB  - OBJECTIVE: To evaluate the local immune response after allergic sensitization and
      challenge in the lungs of mice. METHODS: C57BL/6 mice were sensitized with
      keyhole limpet hemocyanin (KLH) by intratracheal instillation and challenged 2
      approximately 4 weeks later. Bronchoalveolar lavage fluid (BALF) and plasma were
      collected and cells from the lung-associated lymph node (LALN), the lungs and the
      spleen were cultured and collected. Anti-KLH IgA, total IgA and albumin levels
      were measured by ELISA. RESULTS: Intratracheal instillation of KLH induced local
      BAL antigen-specific IgA response, and further challenge expanded this response.
      The ratio of anti-KLH IgA/albumin in BALF was significantly higher than that in
      serum after both sensitization and challenge by KLH. In vitro, cells from the
      LALN and the lungs released anti-KLH IgA after sensitization and challenge by
      KLH, but spleen cells released lower levels of anti-KLH IgA compared to the LALN
      and the lungs. CONCLUSIONS: Allergic sensitization by intratracheal instillation
      of KLH into the mouse lungs induced a local pulmonary response of specific IgA,
      and it was amplified by challenge with KLH. The accumulation of anti-KLH IgA in
      the respiratory lumen was the result of local production but not the result of
      simple transudation or leakage from the serum. The LALN and the lung lymphocytes
      were major sources of anti-specific IgA.

PMID- 11953114
TI  - [The immunotherapeuftc effect of DNA vaccine of mite major allergen on mite
      extract triggered allergic pulmonary diseases].
AB  - OBJECTIVE: To assess the effects of DNA vaccine of mite major allergens on murine
      pulmonary allergic inflammation triggered by mite extract. METHODS: Two
      eukarycyte expression plasmids of Derp 1 and Derp 2 (pDerp 2-IRES-Derp 1 and pCMV
      Derp 1) were constructed. BALB/c mice were divided into four groups: normal
      group, control group, mono-plasmid group and mixture immunization group. The
      latter three groups were immunized with blank plasmid, pDerp 2-IRES-Derp 1 and
      mixture of both pDerp 2-IRES-Derp 1 and pCMV-Derp 1, respectively. The mice were
      sensitized and challenged with mite extract 4 weeks later. Pathological scores,
      bronchoalveolar lavage (BAL) total cell count and differentiation were studied.
      IL-4 and IFN-gamma levels in BAL fluid (BALF) were detected by ELISA. RESULTS:
      Total cell count and eosinophil count in the mixture immunization group [(6 +/-
      4) x 10(5)/ml], 0.05 +/- 0.04 were significantly lower than those in the control
      group [(21 +/- 13)10(5)/ml], 1.80 +/- 1.39, (P < 0.05). IL-4 in BALF in the
      mixture immunization [(168 +/- 233) g/L] group was significantly lower than that
      in the control group [(538 +/- 256) g/L], (P < 0.05). IFN-gamma showed no
      significant changes among different groups (P > 0.05). CONCLUSIONS: DNA vaccine
      of mite major allergens showed inhibitory effect on pulmonary allergic
      inflammation induced by mite extract, and this effect was more prominent in the
      DNA vaccine expressing two allergens than that expressing only one allergen.

PMID- 11953115
TI  - [An experimental study of the effect of bacille calmette-guerin vaccine on the
      production of a rat asthmatic model and its relation with gamma delta T cells].
AB  - OBJECTIVE: To explore the preventive effect of BCG vaccine on asthma attack in
      rats and its relation with gamma delta T cells. METHODS: Wistar rats (n = 10, for
      each group) were immunized with BCG vaccine. After 8 weeks, the rats were
      sensitized and challenged with ovalbumin to establish an asthmatic model. After 3
      weeks, the airway responsiveness (PC(50)) was determined. The percentage of gamma
      delta T cells or alpha beta T cells among total T cells or total lymphocytes and
      the ratio of the mean fluorescence density of CD(28)/gamma delta TCR of gamma
      delta T cell subset in peripheral blood and BALF were detected by flow cytometry,
      immunofluorescence and immunohistochemistry. RESULTS: In the rat asthmatic model,
      the number of BALF eosinophils was increased [(2.5 +/- 1.1) x 10(8)/L vs (0.0) x
      10(8)/L], (P < 0.01). while the PC(50) was decreased [(0.28 +/- 0.10) g/L vs
      (1.36 +/- 0.76) g/L], (P < 0.01). However, the results of the group immunized
      with BCG vaccine were same as the controls [EOS (0.0) x 10(8)/L vs (0.0) x
      10(8)/L], (P > 0.05). PC(50) [(1.28 +/- 0.77) g/L vs (1.36 +/- 0.76) g/L, (P >
      0.05)]. In the asthmatic group, gamma delta T cell/T cell was (32.4 +/- 2.6)%,
      and gamma delta T cell/lymphocytes (28.6 +/- 2.4)%. In the group immunized with
      BCG vaccine, gamma delta T cell/T cell was (41.3 +/- 6.0)% and gamma delta T
      cell/lymphocytes (35.2 +/- 3.3)%. In the asthmatic group immunized with BCG
      vaccine, gamma delta T cell/T cell was (47.3 +/- 8.5)% and gamma delta T
      cell/lymphocytes (39.0 +/- 6.8)%. In the control group, gamma delta T cell/T cell
      was (27.3 +/- 0.8)% and gamma delta T cell/lymphocytes (21.8 +/- 1.9)%, (all P <
      0.01). The ratio of the mean fluorescence density of CD(28)/gamma delta TCR of
      gamma delta T cell subset (0.66 +/- 0.08, 0.88 +/- 0.26, 0.71 +/- 0.15 vs 0.53 +/
      0.06, (all P < 0.01) were increased. CONCLUSIONS: BCG vaccine was shown to be
      able to prevent the production of a rat asthmatic model. gamma delta T cells may
      also have a Th1/Th2 profile, and these cells may be important in the
      immunoregulation of BCG vaccine and the pathogenesis of asthma.

PMID- 11953116
TI  - [16S approximately 23S rDNA internal transcribed spacer sequence analysis and its
      application in mycobacterial identification].
AB  - OBJECTIVE: To study the applicability of the 16S approximately 23S rDNA internal
      transcribed spacer (ITS) sequences in mycobacterial identification. METHODS: The
      16S approximately 23S rDNA ITS sequences of 22 mycobacterial species (30
      reference strains and 16 clinical isolates) were determined by PCR-direct
      sequencing. The sequences determined by this study and those reported in Genbank
      were analysed by Clustal program (MegAlign Package [Windows Version 4.01];
      DNASTAR, Madison, Wis). The percentage similarity of sequence pairs was
      calculated and a cluster analysis dendrogram was constructed by PHYLIP package.
      RESULTS: The 16S approximately 23S rDNA ITS sequences among mycobacterial species
      had highly polymorphism except that Mycobacterium tuberculosis complex (MTC)
      sequences were highly consistent. The similarity between sequence pairs was 30.4%
      to 86.5%. Mycobacterial species could be isolated by cluster analysis dendrogram.
      The results showed that sequence analysis of the 16S approximately 23S rDNA ITS
      can differentiate MTC from nontuberculous mycobacteria (NTM) and identify NTM at
      species level. CONCLUSION: 16S approximately 23S rDNA ITS sequences can be used
      as target genes in mycobacterial identification.

PMID- 11953118
TI  - [The effects of endothelin blockade on renal expression of angiotensin II type 1
      receptor in diabetic hypertensive rats].
AB  - OBJECTIVE: To investigate the changes of angiotensin II type 1 (AT1) receptor in
      the kidney of spontaneously hypertensive rats (SHR) with diabetes and the
      influence of endothelin receptor antagonist bosentan. METHODS: Streptozotocin
      induced diabetic SHR were divided into four groups: groups treated by cilazapril,
      bosentan + amlodipine, and amlodipine rsspectively, and untreated group, 6 rats
      in each group. Six SHR rats and six WKY rats were used as hypertensive and
      normotensive controls respectively. By the end of the 4th week, all rats were
      anasthetized and catheteization was conducted to their right common carotis
      arteries to measure the mean arterial blood pressure and collect blood samples to
      determine the blood sugar and creatinine by biochemical analyzer, and plasma
      angiotensin II level by radioimmunoassay. Then the rats were killed and their
      kidneys were taken. The renal angiotensin II (Ang II) receptor and expression of
      AT1 receptor was determined by RT-PCR and Western blotting. One day before the
      rats were killed, 24-hour urine was collected to determine the urinary protein
      and creatinine. RESULTS: In untreated diabetic SHR, enhanced blood pressure and
      urinary protein excretion, reduced creatinine clearance, as well as significantly
      increased plasma and renal Ang II levels were observed compared with those in WKY
      rats. Immunohistochemistry, Western blotting and semi-quantitatively RT-PCR
      methods showed that the protein and mRNA levels of AT1 receptor in kidney were
      significantly reduced in untreated diabetic SHR compared to those in WKY rats.
      All these abnormalities were attenuated by bosentan + amlodipine and cilazapril
      therapies. CONCLUSION: Bosentan prevents the down-regulation of AT1 receptor in
      the kidneys of diabetic hypertensive rats.

PMID- 11953117
TI  - [The effects of endothelin-1 and selective endothelin receptor-type A antagonist
      on human renal interstitial fibroblasts in vitro].
AB  - OBJECTIVE: (1) To investigate the effects of endothelin-1 (ET-1) on cell
      proliferation of cultured human renal interstitial fibroblasts (hRIFs), and the
      mRNA expression of type I Collagen (Col I), transforming growth factor-beta (TGF
      beta), matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of
      metalloproteinase-1, -2 (TIMP-1, TIMP-2) by hRIFs. (2) To investigate the changes
      of above effects after the hRIFs were pretreated with selective endothelin
      receptor-type A antagonist (ETaRA). METHODS: (1) The proliferation of hRIFs was
      determined by MTT method. (2) The mRNA expression of Col I, TGF-beta, MMP-1, TIMP
      1 and TIMP-2 was detected semiquantitatively with reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: (1) The hRIFs proliferation was
      increased by ET-1 stimulation in dose dependent manner (10(-11) approximately 10(
      7) mol/L, 24 h), and the peak growth level was at the concentration of 10(-7)
      mol/L (P < 0.05). (2) The hRIFs proliferation was significantly increased at 8th
      hour after ET-1 stimulation (10(-7) mol/L) (P < 0.01), and the peak growth level
      was attained at 24th hour (P < 0.01). (3) The mRNA expression of Col I, TGF-beta,
      MMP-1, TIMP-1 and TIMP-2 by hRIFs was upregulated with ET-1 in dose dependent
      manner (10(-11) approximately 10(-7) mol/L, 16 h), and the peak expression level
      was at the concentration of 10(-7) mol/L (P < 0.05). (4) When hRIFs were
      stimulated by ET-1 (10(-7) mol/L), the mRNA expression of Col I and TGF-beta was
      significantly increased at 8th hour (P < 0.05), and the peak expression levels
      were at 24th hour and 8th hour respectively; the mRNA expression of TIMP-1 and
      TIMP-2 was significantly increased at 16th hour (P < 0.05) and reached the peak
      level at 24th hour; the mRNA expression of MMP-1 was significantly increased and
      attained the peak level at 16th hour (P < 0.05). (5) The above effects of ET-1
      were significantly inhibited by ETaRA (P < 0.05). CONCLUSION: The stimulating
      effects of ET-1 on hRIFs proliferation and the mRNA expression of Col I, TGF
      beta, MMP-1, TIMP-1 and TIMP-2, and the inhibiting effects of ETaRA on the above
      effects suggest that ET-1 may participate in the process of renal interstitial
      fibrosis under pathological condition.

PMID- 11953119
TI  - [Cultivation and serial propagation of a new rotavirus causing adult diarrhea in
      primary human embryo kidney cells].
AB  - OBJECTIVE: To investigate the methodology of cultivation of the new rotavirus
      that causes adult diarrhea. METHODS: 10% suspension of new rotavirus positive
      stool specimens in DMEM with 100 microgram/ml trypsin was made and centrifuged at
      the speed of 3 000 rpm for 10 minutes. The supernatant was filtered with 0.45
      micrometer-pore-sized membrane filter, and the filtrate was incubated at 37
      degrees C for 60 minutes. Primary human embryo kidney (PHEK) cells were prepared
      and seeded into roller tubes at the concentration of 1 ml odf cell suspension per
      tube. At 1 hour prior to inoculation, the PHEK cells were rinsed and refed with
      serum-free DMEM. Immediately before inoculation, the DMEM was decanted, and 200
      microliter of prepared filtrate was inoculated into each tube. The tubes were
      incubated at 37 degrees C for 1 hour. At the end of 1 hour 800 microliter of DMEM
      containing trypsin (100 microgram per ml) were added to each tube. The tubes were
      placed in a roller tube apparatus at 37 degrees C for 3 days, removed and frozen
      thawed once. 200 microliter of the cell culture fluids (CCF) were used for
      inoculation of each tube for next virus passage. Detection of new rotavirus from
      CCF was carried out by PAGE, IF, EM and IEM. RESULTS: New rotavirus was
      successfully isolated in cultured cells from 1 of 10 specimens. The isolated
      virus, designated J19, was propagated in PHEK cells for 28 passages. RNA patterns
      of J19 strain were identical to that of original new rotavirus inoculum and
      different from that of group A, B, C rotavirus. PHEK cells infected with the J19
      strain were detected by IF. Infected cells reacted with convalescent antisera to
      the new rotavirus, but did not react with convalescent antisera to ADRV and
      hyperimmune antisera against group A, B rotavirus. Rotavirus particles were
      detected by EM, IEM in infected CCF of J19 strain. Other viral particles were not
      observed. The particles were aggregated with convalescent antisera to new
      rotavirus. CONCLUSION: We were successful in adapting a new rotavirus to serial
      propagation in PHEK cells. The J19 strain is a kind of new rotavirus different
      from group A, B, C rotavirus. This is the first report on the cultivation and
      propagation of the new rotavirus in cultured cells.

PMID- 11953120
TI  - [Inhibition of human gastric cancer metastasis by ocreotide in vitro and in
      vivo].
AB  - OBJECTIVE: To study the effect of somatostatin analogue octreotide on the
      invasion and metastasis of gastric cancer in vitro and in vivo. METHODS: A nude
      mouse model of transplanted in situ human gastric cancer was established by
      implanting SGC-7901 human gastric cancer cells under the skin of nude rats.
      Twelve experimental animals were divided into two groups, 6 in each group:
      octreotide group and control group subcutaneously injected with octreotide of the
      dose of 100 microgram /g(-1) / (-1) and normal saline of the same dose
      respectively for 8 weeks. By the end of the 8(th) week, the animals were killed
      and the tumors were taken out to be examined pathologically. Metastasis was
      observed too. Microvascular density and VEGF expression were examined by
      immunohistochemistry with factor VIII and VEGF antibody. The expression of MMP-2
      gene in gastric cancer cell was examined by gelatin zymography and RT-PCR. The
      upper chamber cavity walls of membrane invasion culture system were covered with
      matrigel and SGC-7901 cells and octreotide were added into the chambers. After 12
      hours' culture, the migration and invasion of cancer cells were observed.
      RESULTS: In the membrane invasion culture system, the numbers of invading and
      migrating SGC-7901 cells were significantly lower in octreotide group than in the
      control group. Metastasis was seen in 4 of the 6 control mice and was seen in
      only one of the 6 octreotide treated mice. The microvascular density was lower in
      octreotide treated mice than in the control. The VEGF and MMP-2 expression was
      inhibited by octreotide. CONCLUSION: Octreotide inhibits the migration and
      invasion of SGC-7901 gastric cancer cells in vitro and inhibits the metastasis of
      cancer in vivo. Tha mechanism may be down-regulation of MMP-2 expression and
      decrease of tumor angiogenesis.

PMID- 11953122
TI  - [Measurement of calcium fluorescent intensity in vital brain slice and mechanism
      of brain injury after circulatory arrest].
AB  - OBJECTIVE: To examine the calcium fluorescent intensity of vital brain slice and
      study the mechanism of brain injury after circulatory arrest. METHODS: Eight pigs
      underwent 90 minutes' deep hypothermic circulation arrest (DHCA) and eight pigs
      underwent retrograde cerebral perfusion (RCP) through superior vena cava and then
      rewarmed for 120 minutes. Vital brain slices were obtained and the calcium
      fluorescent intensity was examined with laser confocal scanning microscope
      (LCSM). The morphological change was examined with light microscope and electron
      microscope. RESULTS: The calcium fluorescent intensity of vital brain slice was
      lower in RCP group than in DHCA group. The calcium fluorescent intensity of vital
      brain slice is correlated with the level of moderate and severe eosinophilic
      degeneration of neuron (r = 0.86, P < 0.05). CONCLUSION: Calcium overload
      contributes to the injury of neuron after DHCA. RCP remarkably attenuates calcium
      overload, thus protecting the brain tissue.

PMID- 11953121
TI  - [Long-term effect of nitric oxide synthase inhibitor on repair of articular
      cartilage defects repairing].
AB  - OBJECTIVE: To discuss the long-term effect of inducible nitric oxide synthase
      inhibitor S-methylisothiourea (SMT) on repair of articular cartilage defects.
      METHODS: Twenty-four adult New Zealand White rabbits with full-thickness defects
      of cartilage created in the trochlear groove of their bilateral femurs were
      divided into three groups randomly, 8 in each group: (1) control group in which
      nothing was filled into the defects; (2) BMP group in which the defects were
      filled with collagen fibrin gel impregnated with recombinant human bone
      morphogenic protein (rhBMP); and (3) SMT group in which the defects were filled
      with collagen fibrin gel impregnated with rhBMP and hypodermic injection of SMT
      (5 mg .(-1) 12 h(-1)) was given. The animals were killed one year later. The
      gross appearance of the defects was assessed. The amount of released NO and the
      activity of NOS were examined by chemical colorimetry. The distribution of
      collagen was examined by immunohistochemistry. The proteoglycan synthesis and
      cell activity was assessed by incorporation of radiolabelled sodium sulphate
      Na(2)(35)SO(4) and bromodeoxyuridine. RESULTS: One year after the defects in SMT
      group showed greater improvement in margin integration, cellular morphology, and
      architecture within defect than those in BMP group and control group (P < 0.01).
      Immunohistochemistry showed that there was less type-I collagen and more type-II
      collagen in SMT group than in the other two groups. Radiolabelled sodium sulphate
      (Na(2)(35)SO(4)) incorporation test showed that the proteoglycan synthesis in
      defects was higher in SMT group than in the other two groups (P < 0.01). BrdU
      incorporation test showed cells in repaired tissue with remarkable proliferous
      activity. CONCLUSION: iNOS inhibitor SMT significantly improves the quality of
      repair of defected cartilage and delays its degradation.

PMID- 11953123
TI  - [Novel full-length cDNA cloning from normal adrenal gland and pheochromocytoma
      and functional prediction].
AB  - OBJECTIVE: To investigate methodology of cloning full-length cDNA from tissues of
      normal adrenal gland and pheochromocytoma and predict their function. METHODS:
      104 samples from normal adrenal gland and 22 samples from pheochromocytoma were
      examined by expressed sequence tags (EST) sequencing, bioinformatics analysis, in
      silico cloning, rapid amplification of cDNA ends and RT-PCR. RESULTS: Among the
      126 samples of novel full-length cDNA cloning 104 were from normal adrenal gland,
      and 22 from pheochromocytoma (PC). Among the novel genes 50 were cloned by direct
      sequencing of clones, 74 by in silico cloning, and 2 by rapid amplification of
      cDNA ends, and the localization of chromosomes was made with UniGene searching
      and radiation hybrid (RH) procedure. Comparison of homology and analysis of motif
      or domain showed that some genes may be important functional genes, such as those
      coding signaling proteins, proteins associated with ion channel, enzymes involved
      in hormone production, important transcription factors, translation initiation
      factors, etc. 7 of the novel full-length cDNAs are new isoforms produced by
      alternative splicing. CONCLUSION: 126 novel full-length cDNAs have been cloned
      from adrenal tissues by large-scale EST sequencing and bioinformatic tools in a
      rather short time, some of which may play an important role in regulating adrenal
      functions and tumorigenesis of adrenal gland.

PMID- 11953124
TI  - [Transfer of cDNAs of platelet factor 4 and N-truncated peptide inhibits solid
      tumor growth in vivo].
AB  - OBJECTIVE: Determine the anti-tumor angiogenic effect of PF4 and p17 - 70 using
      virally mediated gene transfer. METHODS: Full-length PF4 cDNA and p17 - 70 cDNA
      were cloned into retroviral vector (pLXSN). KB was incubated with the supernatant
      of transfected PA317. PCR, RT-PCR and Western blotting analysis was used to
      determine the integration and expression of foreign gene. By MTT method the
      effects of the supernatants of PA317-PF4s and KB-PF4s on the proliferation of
      human umbilical vein endothelial cells (HUVEC) were studied. Tumorigenecity of KB
      PF4 and KBp17 - 70 cells was assayed with xenograft tumor growth in isogenous
      nude mice by examining the growth rate of xenograft, survival, and histochemistry
      of xenograft tumor. RESULTS: Recombinant PF4 and p17 - 70 were able to inhibit
      selectively HUVEC proliferation. Animal survival was significantly prolonged.
      Furthermore, p17 - 70 significantly prolonged animal survival compared with PF4
      group (P < 0.05). CONCLUSION: Transduction of p17 - 70 inhibits solid tumor
      growth through an anti-angiogensis mechanism. Targeted anti-angiogenesis, using
      retroviral-mediated PF4 gene transfer, especially p17 - 70 represents a promising
      strategy for cancer gene therapy.

PMID- 11953125
TI  - [Analysis of telomerase activity in esophageal carcinoma using microdissection
      telomeric repeat amplification protocol assay].
AB  - OBJECTIVE: To investigate the changes of telomerase activities in atypical
      hyperplasia of esophageal mucosal epithelium and esophageal squamous cell
      carcinoma (SCC) and to study the association of telomerase activity with
      differentiation, invasiveness, and lymphatic metastasis of cancer. METHODS: The
      telomerase activities of esophageal SCC tissues, adjacent tissue with dysplasia,
      and normal mucosal epithelium from surgical edge of 45 cases were detected by
      microdissection-TRAP (Telomeric Repeat Amplification Protocol)-silver assay.
      RESULTS: The telomerase activity rates were 79.3% (23/29) in atypical displastic
      epithelium, 82.2% (37/45) in SCC tissue, and only 5% (2/40) in normal epithelium.
      The difference of telpmerase activity between dysplastic and normal esophageal
      epithelia was highly significant (P < 0.01). In the same cancer tissue the
      differences of telomerase activity among cancer nests to different degrees of
      defferentiation and to different depths were not significant (P > 0.05). The
      positive rate of telomerase activity was significantly higher in cases with
      lymphatic metastasis than in cases without lymphatic metastasis (P < 0.05).
      CONCLUSION: The telomerase activities is increased in esophageal SCC tissue and
      adjacent atypical dysplastic tissue. The telomerase activity in SCC tissue is
      related to lymphatic metastasis but not related to cancer differentiation.

PMID- 11953126
TI  - [Immediate immunological effect of China-made recombinant hepatitis B vaccine
      expressed by transgenic Chinese hamster ovary cell line].
AB  - OBJECTIVE: To understand the protective efficacy of China-made recombinant
      hepatitis B vaccine expressed by transgenic Chinese hamster ovary cell line among
      newborns. METHODS: 2 969 newborns in seven townships in Zhengding County, Hebei
      Province, were vaccinated with 10 microgram x 3 doses of China-made recombinant
      hepatitis B vaccine expressed by transgenic Chinese hamster ovary cell line
      according to the 0 - 1 - 6 month schedule from 1 January 1997 to 31 August 1999.
      The newborns were to be vaccinated with the first dose within 24 hours after they
      were born. 1906 serum samples were selected in April 2000 to detect the hepatitis
      B infection markers, including HBsAg, HBsAb and HbcAb by RIA kits. RESULTS: 2 783
      of the 2 969 newborns (93.74%) were vaccinated with three doses, 2 833 of them
      (95.42%) were vaccinated with the first dose within 24 hours after they were
      born. The anti-HBs positive rate was 98.25% (S/N >/= 2.1) or 94.26% (S/N >/=
      10.0), and the geometric mean titer (GMT) value of antibody was 77.64 within the
      first year after the whole course vaccination. Then the antibody level decreased
      gradually with the lapse of time. The HBsAb positive rate was 92.31% (S/N >/=
      2.1) or 68.96% (S/N >/= 10.0), and GMT value was 22.86 within the third year
      after vaccination. The HBsAg positive rates remained less than 1%, the HBcAb
      positive rates and HBV infection rates remained 1% approximately 3% within 3
      years after vaccination. CONCLUSION: The protective efficacy of China-made
      recombinant hepatitis B vaccine is satisfactory.

PMID- 11953127
TI  - [Cerebral venous thrombosis and factor V Leiden mutation].
AB  - OBJECTIVE: To investigate the relationship between factor V Leiden mutation and
      cerebral venous thrombosis in China. METHODS: 20 patients and 50 controls of
      Chinese origin were studied by polymerase chain reaction followed by Mnl I
      restriction enzyme analysis. RESULTS: The PCR products of all the people
      supervised were digested to three segments with the length of 37 bp, 67 bp, and
      116 bp. No factor V Leiden mutation was found in any subjects. CONCLUSION: Factor
      V Leiden mutation is not a crucial risk factor of cerebral venous thrombosis.

PMID- 11953128
TI  - [Antigenicity and physicochemical properties of two human NR1a polypeptides
      related to activation of NMDA receptor].
AB  - OBJECTIVE: To investigate the distribution of antigenic sites in two human NR1a
      polypeptides related to activation of N-methyl-D-aspartate receptor (NMDAR) and
      their physicochemical properties. METHODS: The amino acid sequences of two
      polypeptides, P1, a region containing 151 amino acid residues preceding the first
      transmembrane domain of the human NR1a, and P2 with 144 residues following the
      third transmembrane domain, were obtained from protein database by GOLDKEY
      software (4.0 version). Four parameters including Hopp-Woods and Kyte
      hydrophilicity, Janin accessibility, Karplus-Schulz flexibility, and Welling
      antigenicity were used to determine the antigenic sites, and Prosite programme
      and Chou-Fasman method were employed to analyze their related sequence motifs and
      the secondary structures. Finally, comparison of the comprehensive predictions
      with some of the available experimental information was made. RESULTS: There were
      about six and seven antigenic sites containing 8 approximately 15 residues in the
      P1 and P2 polypeptides respectively. The antigenic sites in P1 were mainly
      located in the amino terminal, but the ones in P2 were dispersed rather
      uniformly. Many sites in P2 polypeptide including some residues in its initial
      part, the amino terminal, showed higher hydrophilicity, accessibility, and
      antigenicity than those in P1. In addition, P1 and P1 were also different in the
      primary and secondary structure. P1 contained more cysteine residues and was rich
      in random coils, while P2 contained more aromatic residues and exhibited mainly
      helical structures. CONCLUSION: Both human NR1a polypeptides related to
      activation of NMDA receptor, P1 and P2, have a certain amount of antigenic sites.
      Compared with P1, P2 may be of higher antigenicity, and may be more easily used
      as a molecular target in immunization intervention to control the activation of
      NMDAR.

PMID- 11953129
TI  - [Study on relationship between leukotrienes and exercise-induced asthma].
AB  - OBJECTIVE: To explore the relationship between leukotriene (LT) and exercise
      induced asthma. METHODS: Twenty-two non-smoking asthmatic patients with a
      reproducible fall in FEV(1) after exercise by least 10% and 10 normal patients
      were enrolled. Urinary levels of leukotriene E4 were measured before and 2 hours
      after exercise. Twelve subjects received cysteinyl LT receptor antagonist
      Zafirlukast (Ancolate) 20 mg twice a day for three days. Standardized exercise
      challenge were performed after 72 hours. End points included (1) area under the
      percent fall in FEV(1) versus time curve (AUC 0-60 min), (2) time to recovery to
      within 5% of the pre-exercise baseline FEV(1) value, (3) and maximum percent fall
      in FEV(1) from pre-exercise baseline. RESULTS: To exercise-induced aothma (EIA)
      group, urinary LTE4 in 2 hours after exercise were higher than that of in before
      exercise, P < 0.01. Urinary leukotriene E4 concentration before and 2 hours after
      exercise were higher than normal subjects. Zafirlukast can caused a significant
      reduction in AUC(0 - 60 min) (Aera under the FEV(1)-time curve for 0 to 60
      minutes after exercise); caused a significant reduction in the maximum percent
      fall in FEV(1); and Zafirlukast resulted in a shorter time to recovery of FEV(1)
      to preexercise baseline. CONCLUSIONS: There was an increase in urinary LTE4
      during the 2 hours after exercise challenge; Zafirlukast can attenuate EIA. The
      results indicate that there is an important role of leukotriene in the
      pathogenesis of exercise-induced asthma.

PMID- 11953130
TI  - [Inhibitory action of CPU86035 on L-type calcium current in single ventricular
      myocyte of guinea pig].
AB  - OBJECTIVE: To investigate the effects of CPU86035, a recently synthesized
      tetrahydroberberine derivative, on the L-type calcium currents (I(Ca.L)) in
      single guinea pig ventricular myocytes. METHODS: The effect of CPU86035 of
      different concentrations (50 approximately 250 micromomol/L) on I(Ca.L) in
      enzymatically dispersed single guinea pig ventricular myocytes was investigated
      by using whole-cell patch-clamp technique. RESULTS: (1) CPU86035 concentration
      dependently inhibited I(Ca.L), with the IC50 at 75 micromol/L. (2) The inhibition
      of CPU86035 on I(Ca.L) was dependent on the holding potential (HP). 75 micromol/L
      CPU86035 inhibited I(Ca.L) by 49% +/- 2% at HP = -40 mV, and 64% +/- 4% at HP = 
      80 mV. (3) The homeostatic activation curve of ICa.L shifted to the right toward
      more positive potentials in the presence of CPU86035, with a V(1/2) of 15.4 mV +/
      0.8 mV compared with that of 15.4 +/- 0.8 mV in the control. (4) The homeostatic
      inactivation curve of I(Ca.L) shifted to the right toward more positive
      potentials in the presence of CPU86035, with a V(1/2) of -12.6 mV +/- 2.7 mV
      compared with that of -19.1 mV +/- 2.5 mV in the control. (5) The recovery from
      inactivation became slower in the presence of CPU86035. CONCLUSION: CPU86035
      strongly inhibits the calcium channel, probably by binding to the channel in
      resting stage.

PMID- 11953131
TI  - [Clinical study on malnutrition and low take of protein and energy in peritoneal
      dialysis patients].
AB  - OBJECTIVE: To study the prevalence and clinical related factors of malnutrition
      and low take of protein and energy in peritoneal dialysis patients. METHODS: We
      examined the nutritional status in 90 clinically stable continuous ambulatory
      peritoneal dialysis (CAPD) patients from four dialysis centers in Beijing,
      including subjective global assessment (SGA), dietary diaries, direct
      anthropometry, biochemistry and so on. The social function and psychological
      status (anxiety and depression) were researched too. These patients were placed
      in various nutritional categorizes based on SGA (i.e. normal nutrition, mild-to
      moderate malnutrition, severe malnutrition). The related factors of malnutrition
      and low take of protein and energy were analyzed through the multivariate
      regression methods. RESULTS: SGA showed the prevalence of malnutrition in our
      CAPD patients was 47.8%, severe malnutrition 13.3%. The mean dietary protein
      intake (DPI), dietary energy intake (DEI), arm circumference (AC), triceps
      skinfold (TSF), arm muscle circumference (AMC), serum albumin (Alb), prealbumin
      (PA), transferring (TF), the normalized protein equivalent of total nitrogen
      appearance (nPNA), lean body mass (LBM) and % LBM were significantly different
      among three groups patients (P < 0.001 approximately 0.05). Logistic multivariate
      regression analysis revealed that DPI (P < 0.05), DEI (P < 0.05) and Tccr (P <
      0.01) are negatively correlated with malnutrition, duration of dialysis (P =
      0.12) and diabetes (P < 0.05) positively correlated with malnutrition. The mean
      DPI and DEI were (0.74 +/- 0.26) g . kg(-1) .d(-1), (113 +/- 29) kJ . kg(-1) . d(
      1) respectively. In the linear multivariate regression, anxiety scores (P < 0.01)
      were negatively correlated with DEI, taking exercise (P < 0.05) positively with
      DEI and depression scores (P < 0.01) negatively with DPI. There were 72 (80%)
      patients with anxiety of different grades, 14 (15.6%) patients with depression of
      different grades. CONCLUSION: Malnutrition is prevalence in our CAPD patients.
      Low take of protein and energy, reduced residual renal function and Tccr, long
      duration of dialysis and diabetes may remarkably influence on malnutrition in our
      CAPD patients. Anxiety, depression and less exercise may play an important role
      in low take of protein and energy.

PMID- 11953132
TI  - [Expression and immune response to hepatitis C virus core gene combined hepatitis
      B virus core gene with two multiple cloning sites vector].
AB  - OBJECTIVE: To develop a HCV combined HBV DNA-based therapeutic vaccine. METHODS:
      The HBV core gene and HCV core cDNA were inserted into the eukaryotic expression
      vector with two multiple cloning sites mammalian expression vector, which can be
      used for expression of two foreign genes, under the CMV promoter and RSC promoter
      respectively (named pRSC-HBV/HCV). Cellular expression of pRSC-HBV/HCV was
      assessed following transfection into SP2/0 cells. The Balb/c mice were immunized
      by multiple sites intramuscular injection with pRSC-HBV/HCV and the immune
      responses were detected. RESULTS: The 21-kd and 14-kd core protein was observed.
      Both anti-HBc IgG and anti-HCV core Ab were detected in all immunized mice.
      Strong CTL activity of splenocytes against SP2/0 cells expressing both HBV and
      HCV core proteins were measured in immunized mice both in vitro and in vivo.
      CONCLUSION: The investigation demonstrated that pRSC-HBV/HCV could generated both
      humoral immune response and Strong CTL activity against HBcAg and HCV
      nucleocapsid in mice.

PMID- 11953133
TI  - [The study on heterogeneity of hepatitis B virus DNA].
AB  - OBJECTIVE: To investigate the HBV quasispecies groups in the patients with
      chronic HBV infection. METHODS: Specific primers ware synthesized according to
      HBV strain found in China, the preC/C gene, reverse transcriptase region, whole S
      region, X gene and whole genome ware amplified by PCR method from the serum of 18
      patients with chronic HBV infection, and then the PCR products were subcloned
      into pGEM Teasy vectors. Positive clones with target sequences were selected out
      for sequencing. Sequence comparison of the selected clones ware made to find the
      difference. RESULTS: The homology between clones from one patient of preC/C gene,
      reverse transcriptase of polymerase region, whole S region, X gene and whole
      genome are 98.0% approximately 99.1%, 98.7% approximately 99.3%, 97.5%
      approximately 100%, 93.0% approximately 98.2% and 96.6% approximately 97.5%,
      respectively. There was a high-frequency A83 substitution and core antigen
      internal deletion (CID) in preC/C region. Substitution, deletion and frame-shift
      by insertion or deletion of short sequence were found in 4 open reading frames.
      Deletion in X gene (Core promoter, CP) will not only result in the polymorphism
      of X protein at the carboxyl end, but also regulate the expression of HBeAg.
      Coding sequence of truncated middle surface antigen and defective HBV genome
      could also be detected in this study. CONCLUSION: There are HBV quasispecies
      groups in patients with chronic HBV infection. Hot deletion region in X region
      (CP) will influence the prognosis of the HBV infection. Individually
      characterized substitutions in amino acid sequence of viral protein is worthy of
      further study.

PMID- 11953134
TI  - [A study of the engraftment, expansion and differentiation of human hematopoietic
      stem cells in goats].
AB  - OBJECTIVE: To establish a human/goat hematopoietic stem cell (HSC) xenogeneic
      transplant model and to probe the engraftment, expansion and differentiation of
      human HSC in vivo. METHODS: Human HSCs were isolated from human umbilical cord
      blood and 1 x 10(5) human HSCs were in utero transplanted into 50 fetal goats at
      the 55 - 65 the gestation days. The engraftment, expansion and differentiation of
      human HSCs in goats were determined by FACS analysis, PCR and PCR-Southern blot
      hybridization at various intervals after birth. RESULTS: Hematopoietic chimerism
      occurred certainly in 35 of 39 live-born recipients. On average, The proportion
      of human hematopoietic cells in goat blood was 1% approximately 3% and remained
      phenotypically stable for at least 10 months. The human hematopoietic cells
      circulated in goat blood expressed CD34, CD14, CD20 and glycophorin A (GPA) but
      did not express CD3, CD4, CD7, CD8 and CD56 or expressed them at a very low
      level. CONCLUSION: The number of human HSC can be effectively expanded 1 000 - 10
      000 fold. Human HSCs in goats undergo a limited differentiation. Our human/goat
      HSC xenogeneic model provides a useful way for the investigation of HSC
      transplantation, expansion and differentiation in vivo.

PMID- 11953135
TI  - [Effects of recombinant human bone morphogenic protein-2 and hyaluronic acid on
      invasion of brain glioma in vivo].
AB  - OBJECTIVE: To investigate the effects of recombinant human bone morphogenic
      protein-2 (rhBMP-2) and hyaluronic acid (HA) on the invasion and metastasis of
      rat brain glioma in vivo. METHODS: C6 rat glioma cells were transfected with the
      plasmid vector named pEGFP-N3 which contained an enhanced green fluorescent
      protein (EGFP) gene. The stable cell clones which expressed EGFP protein were
      stereotactically injected into the brain parenchyma of SD rats in order to
      establish a xenotransplanted tumor model. After rhBMP-2 and HA were administered
      in the xenotransplanted tumor model at different dosages, their effects on glioma
      invasion and metastasis were observed by pathology, flow cytometry fluoresclnec,
      and electronmicvoscopy. RESULTS: EGFP-transfected C6 glioma cells gave off green
      fluorescence in vivo and in vitro. Area with tumor and area without tumor could
      be easily distinguished by fluorescence microscopy. Even distant micrometastasis
      and invasion at single-cell level could be detected. 10 microliter rhBMP-2 of the
      concentration of 5 microgram/ml inhibited C6 tumor invasion, while 10 microliter
      hyaluronic acid of the concentration of 100 microgram/ml evidently promoted the
      tumor invasion. CONCLUSION: EGFP-transfected C6 cells can be transplanted into
      rats' brain so as to establish an excellent experimental animal model in the
      research on invasion and metastasis of brain glioma in vivo. RhBMP-2 inhibits
      tumor invasion, while HA evidently promotes its invasion.

PMID- 11953137
TI  - [Autologous skeletal myoblast cardiomyoplasty, an experimental study].
AB  - OBJECTIVE: To investigate the possibility that skeletal muscle satellite cells
      implanted into injured myocardium in different time after myocardial infarction
      differntiate into cardiac-like muscle fibers, thus repairing the damaged heart
      muscle. METHODS: Coronary ligation combined with C-shape cryoinjury was performed
      upon 16 dogs to make a myocardial infarction (MI) area I on left ventricular free
      wall and an area II was made by cryoinjury near MI area I. Then the dogs were
      divided into two groups, 8 in each group. In group A the satellite cells (6 x
      10(7)) labeled with Diamidino-phenyl-indole (DAPI) were collected and resuspended
      in 5 ml of M199 and then were injected into the two. MI areas of the same donor
      dogs through the coronary artery and heart wall. In group B, the collected
      satellite cells (6 x 10(7)) were implanted into the two MI areas in the same way
      under second thoracotomy 10 approximately 14 days after myocardial infarction was
      caused. Four weeks after implantation the dogs were sacrificed under general
      anesthesia. The heart specimens were processed for histological examination.
      RESULTS: Small area of MI was successfully made by combination of coronary
      ligation and C-shape cryoinjury or by pure cryoinjury. Discrete fluorescence
      could be seen in the MI area I of group A under fluorescent microscope, however,
      no fluorescence was seen in the MI area I of group B. Line-shaped fluorescence
      was found in the MI area II of both groups under fluorescent microscope. No
      striated muscle was found by light microscope and transmission electron
      microscope. CONCLUSION: Cellular cardiomyoplasty with satellite cell implantation
      is still immature for clinical use now. Further research must be done in the
      future.

PMID- 11953136
TI  - [Cloning of a novel gene, ANGPTL4 and the functional study in angiogenesis].
AB  - OBJECTIVE: To clone a novel HCC-related gene and study its functions. METHODS:
      Using a combination of cell growth based functional screening of human placental
      cDNA library and RACE, a novel gene, angiopoietin-like 4 (ANGPTL4) was isolated.
      The gene was mapped by RH-PCR; also it was expressed with E. coli. Effects on
      angiogenesis was studied by MTT assay, in vitro wound migration assay, in vitro
      invasion assay, in vitro tube formation assay and in vivo mouse matrigel plug
      assay. RESULTS: ANGPTL4 was cloned and mapped in 19p13.3. ANGPTL4 had no
      significant effect on proliferation of PAEC (P = 0.0504), while it can
      significantly stimulate migration and invasion of PAEC with the dose of 2
      microgram/ml (P < 0.05) and promote in vitro tube formation of PAEC and
      angiogenesis of mouse in vivo. CONCLUSIONS: ANGPTL4 can stimulate angiogenesis.

PMID- 11953138
TI  - [Interleukin-10 inhibits the activation of cultured rat hepatic stellate cells
      induced by Kupffer cells].
AB  - OBJECTIVE: To investigate the effect of interleukin-10 (IL-10) on the activation
      of cultured rat hepatic stellate cells (HSC) induced by Kupffer cells (KC) and
      relevant mechanisms. METHODS: HSC and KC were isolated and purified from rat
      liver by collagenase IV perfusion and density gradient centrifugation with
      Nycodenz. After primary culture for 2 days, HSC and KC were divided randomly into
      three groups: HSC group, KC group and HSC + KC group (coculture group), then were
      stimulated by IL-10 of concentrations of 2 ng/ml or 20 ng/ml respectively. After
      2 days, the proliferation of HSC were determined with (3)H-TdR incorporating
      test, the expression of alpha-smooth muscle actin (alpha-SMA) in HSC was detected
      by Western blotting, and tumor necrosis factor-alpha (TNF-alpha) protein
      concentration in the supernatant was determined by ELISA. RESULTS: IL-10 showed
      no significant effect on HSC proliferation (P > 0.05) and alpha-SMA expression (P
      > 0.05) in HSC group. The levels of proliferation and alpha-SMA expression of HSC
      in coculture group were 2.4 times (P < 0.001) and 6 times (P < 0.001) higher
      respectively than that in HSC groups. In coculture group, HSC proliferation and
      alpha-SMA expression were decreased by 23% (P < 0.001) and 35% (P < 0.05)
      respectively after stimulation of 2 ng/ml IL-10, and were decreased by 33% (P <
      0.001) and 49% (P < 0.05) respectively after stimulation of 20 ng/ml IL-10 in a
      dose dependent way. TNF-alpha was not detected in HSC group. The level of TNF
      alpha in HSC + KC coculture group was 74% higher than that in KC group (P <
      0.01). 2 ng/ml and 20 ng/ml IL-10 reduced the TNF-alpha level by 27% (P < 0.01)
      and 36% (P < 0.01) respectively in coculture group, and reduced the TNF-alpha
      level by 29% (P < 0.05) and 42% (P < 0.01) respectively in KC group in a dose
      dependent way. CONCLUSION: IL-10 reduces the level of TNF-alpha secreted by KC
      dose-dependently. Through reducing cytokine production by KC, IL-10 inhibits the
      activation of cultured rat HSC induced by KC, which may play a protective role
      against liver fibrosis.

PMID- 11953139
TI  - [Effect of brain extract of hypoxic preconditioned mice on activity of ATP
      sensitive potassium channel in hippocampal neurons].
AB  - OBJECTIVE: To observe the effect of brain extract taken from hypoxic
      preconditioned mice on activity of ATP sensitive potassium channel (K(ATP)).
      METHODS: Changes of outward potassium current (Ik) were recorded by whole cell
      patch clamp in acutely dissociated rat hippocampal neurons prior to and after
      application of glibenclamide (GLI). the brain extract of hypoxic preconditioned
      mice. RESULTS: Ik was significantly increased by addition of sodium cyanide
      (NaCN) (1448-->2381 pA) and the increase was significantly inhibited (2381-->1725
      pA) by application of glibenclamide (GLI). Similar increase and decrease were
      shown when adenosine (ADO) and GLI were added (1399-->2584-->1703 pA). The
      current was also significantly increased and inhibited, respectively, when brain
      extract of preconditioned mice who had been exposed to hypoxian 4 times and GLI
      were applied (1298-->2413-->1713 pA). No significant change was seen when brain
      extract taken from mice exposed to hypoxia only once was added. CONCLUSION:
      K(ATP) of hippocampal neurons is activated by ADO-like neuroactive substances in
      the brain extract of hypoxic preconditioned mice.

PMID- 11953140
TI  - [Influence of TGF beta(1) on expression of Smad7 mRNA and protein in rat liver
      cells].
AB  - OBJECTIVE: To investigate the influence of exogenous transforming growth factor
      beta 1 (TGFbeta1) on growth and signal inhibitor Smad7 protein and its mRNA in
      BRL cells (rat liver cell line). METHODS: BRL cells were incubated with TGFbeta1
      and divided into 0 minute group, 90 minute group and 24 hour group according to
      the time of incubation with TGFbeta1. Morphologic changes were observed. The
      expression of Smad7 mRNA and protein was investigated by reverse transcriptase
      polymerase chain reaction (RT-PCR), Western blotting, and immnuohistrochemistry.
      RESULTS: Growth stagnancy and morphologic change of cells was not seen among the
      three groups. The expression levels of Smad7 mRNA was the highest in 90-minute
      group and the lowest in 0-minute group, and the 24-hour group took the second
      place. Most of the Smad7 immune positive granules were observed in cytoplasm.
      CONCLUSION: TGFbeta1 does not induce growth stagnancy in BRL cells during the
      period of 90 minutes to 24 hours. There is a relation of effectiveness for a
      given period of time between the level of Smad7 and TGFbeta1 stimulation.

PMID- 11953141
TI  - [Correlation between polymorphism of IL-4 and IL-10 gene promoter and childhood
      asthma and their impact upon cytokine expression].
AB  - OBJECTIVE: To investigate the correlation between the polymorphism of IL-4 and IL
      10 gene promoters and the susceptibility of Chinese children to asthma and to
      study the impact of such polymorphism upon cytokine production. METHODS: The data
      of medical history, pulmonary function, hypersensitive test, and serum IgE were
      recorded among 168 unrelated Chinese children with asthma aged 5 approximately
      15. Four polymorphism sites of IL-4 and IL-10 gen promoter regions were
      determined by PCR/RFLP. The peripheral blood monocyte (PBMC) was cultured and
      stimulated by lipopolysacchride (LPS). Then the contents of IL-4 and IL-10 gene
      promoter regions were determined by ELISA. 53 age-matched children without asthma
      were used as control. RESULTS: (1) The allele frequencies of-598 (C/T) site of IL
      4 gene promoter was significantly different between Chinese children and children
      of Caucasian and Afro-American origin (P = 0.01). The allele frequency of -1082
      (G/A) site, -819 (C/T) site, and -592 (A/C) site in IL-10 gene promoter was
      significantly different between Chinese children and their British counterparts
      (P = 0.01). (2) The serum total IgE level was significantly different among
      children with different allelic sites in IL-4 and IL-10 gene promoters. A allele
      in IL-10 - 1082 (G/A) site and T allele in IL-10 - 819 (C/T) site -1082 were
      associated with elevated total serum IgE (P < 0.01, OR = 3.16; P < 0.05, OR =
      1.84). (3) The IL-10 level in the supernatant of PBMC culture of children with
      homozygous genotypes of -819 TT and ATA/ATA in IL-10 gene promoter after
      stimulation of LPS was the lowest in comparison with those in the supernatant of
      PBMC culture of children with other genotypes (all P < 0.05). (4) No correlation
      was found between -589 (C/T) site in IL-4 gene promoter and asthma. There was no
      significant difference between the increase of IL-4 level in the supernatant of
      PBMC culture of children with the two different homozygous genotypes of IL-4 gene
      promoter. CONCLUSIONS: (1) There is no significant correlation between the
      polymorphism sites in IL-4 and IL-10 gene promoters and the susceptibility to
      asthma among Chinese. (2) The polymorphism of IL-10 gene promoter may be an
      important candidate gene for severity of asthma. The allele -819T plays an
      important role in increase of the total serum IgE by reducing the upregulation of
      IL-10 gene expression.

PMID- 11953142
TI  - [Hyperhomocysteine, methylenetetrahydrofolate reductase gene, and other risk
      factors in ischemic stroke].
AB  - OBJECTIVE: To investigate the relation between plasma homocysteine (Hcy) and
      cerebral ischemic diseases and that between polymorphism of
      methylenetetrahydrofolate reductase (MTHFR) gene and cerebral ischemic diseases.
      METHODS: The plasma homocysteine (Hcy) and genetic polymorphism of MTHFR among
      forty-nine cases with ischemic cerebral diseases, including 25 with acute
      cerebral infarction (CI) and 25 with transient ischemic attacks (TIA), were
      investigated. Fifty-five age- and sex-matched healthy persons were used as
      controls. All the subjects underwent brain CT, carotid duplex, transcranial
      Doppler examination, plasma Vitamin B(12) and folic acid examination, besides
      examination of plasma Hcy and nucleotide 677 MTHFR genotypes. The effects of age,
      liver function, renal function, smoking, drinking, plasma vitamin B(12), and
      folic acid were analyzed. RESULTS: The mean plasma Hcy was significantly higher
      in the CI group and TIA group (17.4 +/- 7.6 micromol/L and 16.6 +/- 5.2
      micromol/L) compared with that in the control group (12.6 +/- 5.2 micromol/L, P <
      0.01). The odds ratio was 3.26 (95% CI, 1.05 approximately 10.09, P < 0.01). The
      Hcy concentration was significantly higher in persons with T/T genotype than in
      those with C/C or CT. There was no significant difference of frequency of mutant
      alleles (T) in site 677 of MTHFR gene and in frequency of homozygote T/T among
      the patients and controls (52.0% vs. 44.0%, P < 0.05 and 26% vs. 20.0%, P >
      0.05). The difference of Hcy was significant between those being T/T homozygotic
      and those not being T/T homozygotic in different groups. There was no statistical
      correlation between plasma Hcy level and extra- and intracranial stenosis of
      cerebral artery. Increase of BUN and smoking were significantly correlated with
      increase of Hcy (P < 0.05). The concentrations of plasma Vitamin B(12) and folic
      acid were significantly correlated with that of Hcy. CONCLUSION: Homozygote of
      mutant MTHFR gene C677T causes hyperhomocystinemia. There is a significantly
      association between hyperhomocystinemia and ischemic cerebrovascular disease. The
      frequency of mutation in MTHFR genotype is higher in Chinese than in Caucasians.
      In addition to gene mutation, renal function and smoking are related to increase
      of plasma Hcy. No correlation between genotype of MTHFR and stroke is found.

PMID- 11953143
TI  - [An analysis of double autologous hemopoietic stem cell transplantation for
      hematological malignancies].
AB  - OBJECTIVE: To analyse the clinical efficacy of the double autologous hemopoietic
      stem cell transplantation (DAHSCT) for hematological malignancies. METHODS: 19
      hematological malignant disease patients received the first AHSCT within 12
      months after diagnosis. The first conditioning regimen was VP-16 or Ara-C, CTX +,
      TBI, nine of them received BCNU additionally. All patients received the second
      AHSCT in 4 to 10 months after the first AHSCT. The second conditioning regimen
      was VP-16 (or Ara-C), CTX +, Mel. RESULTS: All patients had rapidly hemopoietic
      reconstitution, the first hemopoietic reconstitution is faster than the second.
      There was no AHSCT related death. The median follow up duration was 1078 days. 12
      of the 19 patients were still alive during the analysis. The 3-year disease-free
      suvival (DFS) was 63% +/- 10%. Those patients who had more blasts in bone marrow
      at the second AHSCT than the first AHSCT had greater probability to relapse.
      CONCLUSION: DAHSCT can be safety performed as an important treatment method in
      hematological malignancies.

PMID- 11953144
TI  - [Study of mechanism of vasoplegic syndrome for open heart surgery].
AB  - OBJECTIVE: To study the mechanism of vasoplegic syndrome after cardiac surgery.
      METHODS: Twenty-four rabbits were anesthesized intravenously. Pulmonary artery,
      renal artery, and carotid artery were isolated and arterial rings with the length
      of 3.0 mm, 8 rings for each artery, were resected and incubated in Kreb solution
      at temperature of 37 degrees C for one hour. The intactness of endothelium of
      arterial rings was examined. Those losing intactness were abandoned. The change
      of angiostasis at different temperatures was recorded with vascular tone
      software. The arterial rings of different groups were incubated in Kreb solution
      at the temperatures of 37 degrees C, 30 degrees C and 24 degrees C for 30
      minutes. Noradrenalin of different concentrations was added into the solution at
      different temperatures. And then the angiostasis was recorded. RESULTS: At low
      temperature, the vascular tone of the three arteries (Fpulmonary artery = 69.909,
      Frenal artery = 131.192, Fcarotid artery = 50.663, P < 0.001) and contraction in
      response to noradrenline of pulmonary artery (F = 269.121, P < 0.001), renal
      artery (F = 250.535, P < 0.001) and carotid artery (F = 250.535, P < 0.001) were
      lower than at normal temperature. CONCLUSION: Hypothermia may be one of the
      causes of vasoplegic syndrome after cardiac surgery.

PMID- 11953145
TI  - [Calcitonin gene-related peptide induces chemokine interleukine-8 synthesis in
      human monocytes].
AB  - OBJECTIVE: To study the effect of calcitonin gene-related peptide (CGRP) on the
      function of immune cells. METHODS: Human monocytes were cultured with calcitonin
      gene-related peptide in vitro and activated with lipopolysaccharide (LPS). The IL
      8 level in the supernatant was measured with ELISA and the IL-8 mRNA expression
      in monocytes was observed by reverse transcription polymerase chain reaction (RT
      PCR). The chemotactic activity of monocytes to neutrophils and lymphocytes was
      analyzed with micro-chemotacxis chamber. Chemotactic index (CI) was calculated by
      the formula: number of monocytes migrating to the underside of membrane in the
      LPS + CGRP group/number of monocytes migrating to the underside of membrane in
      the control group. CGRP receptor antagonist CGRP8 - 37 was added into the culture
      to study the effect of CGRP. Blank control and cultures of monocytes with LPS or
      with CGRP only were used as controls. RESULTS: The level of IL-8 protein in the
      supernatant of the LPS + CGRP group was 1 120 pg/ml +/- 14.80 pg/ml,
      significantly higher than those in other groups (670 pg/ml +/- 15.10 pg/ml in LPS
      + CGRP + CGRP8 - 37 group). The expression of IL-8 mRNA in the LPS + CGRP group
      was the highest (IL-8/beta-actin = 1.845 +/- 0.587), IL-8/beta-actin in the LPS +
      CGRP + CGRP8 - 37 group was1.339 +/- 0.434. The chemotactic activities of the
      monocytes to neutrophils and lymphocytes were enhanced in the LPS + CGRP group
      (CI = 3.78 +/- 0.08 to neutrophils and CI = 3.4 +/- 0.27 to lymphocytes). The CI
      values were 1.15 +/- 0.31 and 1.21 +/- 0.06 respectively in the LPS + CGRP + CGRP
      8 - 37 group. CONCLUSION: CGRP in the peripheral nerve ending induces monocytes
      to synthetize and secret chemotactic factor IL-8 and enhance the chemotactic
      activity of monocytes, thus promoting the directional migration and aggregation
      of neutrophils and lymphocytes to foci of inflammation.

PMID- 11953146
TI  - [Surgical treatment of left iliac compression syndrome].
AB  - OBJECTIVE: To explore the remedial indications, operational methods, and
      perioperational treatment of iliac compression syndrome (ICS) in left extremity.
      METHODS: The clinical data of 46 patients with symptoms of chronic swelling or
      varicose vein in left lower extremity and the diagnosis of left ICS were
      analyzed. Interventional treatment, iliac vein loosening by laparotomy and right
      iliac artery anastomosis behind left iliac vein lesion, and vascular graft
      orthotopic transplantation were performed in 32, 8 and 6 cases respectively.
      Surgical management of saphenous vein and femoral valves were performed
      simultaneously or by secondary operation in 41 cases. 36 patients were
      complicated by acute left lower extremity deep venous thrombosis (DVT), of which
      resection of lesion in left iliac vein and vascular graft orthotopic
      transplantation after thrombectomy, and iliocaval bypass were performed in 25 and
      11 cases respectively. After treatment, the patients were followed up for 6 - 66
      months. RESULTS: No operation death and acute pulmonary embolism was found among
      the patients. The treatment showed a good long-term effect. CONCLUSION: Lesions
      of left iliac vein are the important cause of swelling and varicose veins and
      acute DVT in left lower extremity and should be managed as early as possible.
      Interventional treatment and surgery are effective.

PMID- 11953147
TI  - [Phrenic nerve conduction in amyotrophic lateral sclerosis patients].
AB  - OBJECTIVE: To investigate the features and application of phrenic nerve
      conduction in amyotrophic lateral scle-rosis (ALS) patients. METHODS: The latency
      and amplitude of diaphragmatic compound muscle action potential (DCMAP) were
      recorded among 44 ALS patients and 31 control subjects with surface electrodes
      after the cervical part of phrenic nerve was stimulated with electricity. The
      percentage of forced vital capacity (%FVC) was examined in 28 ALS patients
      simultaneously. RESULTS: Right and left phrenic distal motor latencies (PDML) of
      ALS patients were 8.4 ms +/- 2.2 ms and 7.6 ms +/- 1.4 ms respectively, longer
      than those of the controls, and the logarithmic value of amplitudes among ALS
      patients was 2.68 +/- 0.37, lower than that among the controls. Take the right
      side for example, although PDML was correlated with %FVC, it had no correlation
      with clinical respiratory dysfunction. Neither %FVC nor clinical respiratory
      dysfunction was correlated with the amplitude of DCMAP. The rate of abnormal PDML
      (47.7%) was higher than the rate of clinical dyspnea (25%). CONCLUSION: PDML is a
      sensitive index in phrenic conduction parameter reflecting respiratory
      dysfunction in ALS. Only when the PDML is combined with the central motor
      conduction time of the diaphragmatic motor evoked potential the nervous system
      basis of the respiratory disturbance in ALS can be revealed.

PMID- 11953148
TI  - [Association between dystrophin and neuronal nitric oxide synthase in muscles of
      progressive muscular dystrophy].
AB  - OBJECTIVE: To study the association between dystrophin and neuronal nitric oxide
      synthase in muscles of progressive muscular dystrophy patients and the role of
      deficiency of nNOS in pathogenesis of muscular dystrophy. METHODS: NADPH
      diaphorase enzyme histochemistry and anti-nNOS, anti-dystrophin, and anti-alpha,
      beta, gamma, delta-sarcoglycan antibody immunohistochemistry were used to analyze
      the muscle specimens from progressive muscular dystrophiy patients. RESULTS: Both
      nNOS and dystrophin were absent in the sarcolemma region of Duchenne muscular
      dystrophy (DMD) patients. Dystrophin was reduced, and nNOS was absent or reduced
      in the sarcolemma region of Becker muscular dystrophy (BMD) patients. Both nNOS
      and dystrophin were expressed normally in the sarcolemma region of limb girdle
      muscular dystrophy (LGMD) patients. CONCLUSION: Deficiency of nNOS is associated
      with deficiency of dystrophin in the sarcolemma. Dystrophin may have a novel role
      in localizing nNOS to sarcolemma and regulating the expression of nNOS. Aberrant
      regulation of nNOS may contribute to degeneration of muscle fibers in DMD.

PMID- 11953149
TI  - [Mitochondrial myopathy and mitochondrial encephalomyopathy].
AB  - OBJECTIVE: To investigate the symptomatic, biochemical, and pathological
      characteristics of mitochondrial myopathy and mitochondrial encephalomyopathy.
      METHODS: Physical examination, electromyography, electroencephalography, cranial
      CT or MRI, serum enzymological examination, and light microscopy and electron
      microscopy of muscle biopsy specimens were made among twenty-one in-patients with
      the diagnosis of mitochondrial myopathy and mitochondrial encephalopathy. All the
      patients were followed up for more than 5 years. RESULTS: Four patients died of
      lung infection, epilepticism or multiple organ failure 3, 4, 6, and 8 years after
      the onset of disease. One patient had already survived for 12 years. Among the 6
      patients with the original diagnosis of mitochondrial myopathy, the diagnosis of
      two was changed as myoclonus epilepsy with ragged fiber (MERRF) 5 and 6 years
      after the onset. Among the seven patients whose disease was originally diagnosed
      as chronic progressive external ophthalmoplegia the diagnosis was changed as
      mitochondrial encephalomyopathy with lactic acidemia and stroke like episodes
      seven years after the onset. CONCLUSION: It is not difficult to diagnose
      mitochondrial myopathy and mitochondrial encephalomyopathy based on the
      symptomatical, biochemical, and pathological characteristics. However, the
      clinical manifestations of these diseases may change during the progress of the
      disease. Follow-up is highly recommended.

PMID- 11953150
TI  - [Loss of heterozygosity fine mapping of chromosome 17p13 in transitional cell
      carcinoma of human urinary bladder].
AB  - OBJECTIVE: To determine the frequency and common deletion region of allelic
      losses on chromosome 17p13 in transitional cell carcinoma (TCC) of human urinary
      bladder so as to provide clues for isolation of candidate tumor suppressor genes
      associated with TCC of urinary bladder. METHODS: Loss of heterozygosity (LOH)
      analysis was made on 44 samples of surgically resected primary TCC by using 13
      microsatellite markers to map the regions frequently deleted on chromosome 17p13.
      The relationship between the LOH in each locus and pathological grade and stage
      was analyzed. RESULTS: Out of the 44 samples, 35 (79.5%) showed allelic loss in
      at least one of the 17p13 loci. The highest frequency of LOH (41.4%, 12/29) was
      at D17S513 in 17p13.2, the second highest frequency of LOH (40.5%, 17/42) was at
      D17S1308 in 17p13.3, and the lowest (14.3%, 4/28) was at D17S261 in 17p13.1. The
      most frequent LOH loci were mainly located in three regions: D17S695-D17S1308 in
      17p13.3, D17S1533-D17S831 in 17p13.2, and TP53 in 17p13.1. Among them only the
      LOH frequency of TP53 locus was positively correlated to the grade (chi(2) =
      5.104, P < 0.05) and stage (chi(2) = 5.382, P < 0.05) of TCC of unrinary bladder.
      CONCLUSION: In 17p13 region, except for TP53 gene, still exist two candidate
      tumor suppressor genes located in D17S695-D17S1308 and D17S1533-D17S831 involved
      in the carcinogenesis of TCC of urinary bladder. LOH of TP53 locus may be one of
      the later events in TCC, and LOH in 17p13.3 and 17p13.2 may be the early events
      of TCC of uninary bladder.

PMID- 11953151
TI  - [Epidemiology of twin and twin with birth defects in China].
AB  - OBJECTIVE: To investigate the incidence of twin and twin with birth defect (BD)
      and with neural tube defect (NTD) in China. METHODS: A prospective monitoring was
      conducted among the perinatal infants born in 945 hospitals in 20
      provinces/municipalities/autonomous regions in China during the period from 1
      October 1986 to 30 September 1987 to count up the numbers of twins and of twins
      with BD or NTD. RESULTS: 1 243 284 infants were born during this period. Among
      these perinatal infants there were 12 715 pairs of twins with an incidence of
      10.23%. The incidence rates of twin with BD and of twin with NTD were 36.81% and
      5.27% respectively. There was no difference in incidence rate of twin among
      different parts of the country and between urban area and rural area. The
      incidence rate of twin was the highest among the women aged 20 approximately 39,
      among primipara, and in October and November. The incidence rate of twin with BD
      showed no difference among different seasons, parities, and parts of the country
      and between urban area and rural area. Most of twin with BD occurred at the age
      20 approximately 39. Most twins with NTD were born in the northern provinces and
      rural area. The incidence rate of twin with NTD was correlated with season, most
      twins with NTD being born in November, and was no correlated with age and parity
      of the mother. CONCLUSION: The incidence of BD, especially the incidence of NTD,
      among twins is significantly higher than that among total perinatal infants in
      China. Prenatal monitoring is important for twin pregnancy.

PMID- 11953152
TI  - [Expression of growth hormone receptor and its mRNA in cirrhotic livers].
AB  - OBJECTIVE: To investigate the expression of growth hormone receptor in human
      cirrhotic livers. METHODS: Radio-ligand binding assay and reverse transcription
      polymerase chain reaction (RT-PCR) were used to examine the expression of growth
      hormone receptor and its mRNA in cirrhotic liver tissues near cancer in 32 cases
      and cirrhotic liver cells near cancer of 6 patients undergoing radical resection
      of liver cancers. The results were compared with those in 5 specimens of normal
      liver tissue and 3 specimens of normal liver cells. RESULTS: The binding capacity
      of growth hormone receptors in human cirrhotic liver tissues was significant
      lower than that in normal control [RT, (22.4 +/- 5.0) fmol/mg protein, n = 32
      versus (41.3 +/- 5.3) fmol/mg protein, n = 5; P < 0.05] and decreased further
      along with the aggravation of cirrhosis (P < 0.05). The number of binding sites
      of growth hormone receptors in human cirrhotic liver cells were significantly
      lower than that in normal control [Site, (2.40 +/- 0.93) x 10(4)/cell, n = 6
      versus (4.68 +/- 1.14) x 10(4)/cell, n = 3; P < 0.05]. The expression of growth
      hormone receptor mRNA in human cirrhotic liver tissues was significant lower than
      that in normal control [riOD, 30.8% +/- 8.2%, n = 32 versus 44.93% +/- 6.25%, n =
      5; P < 0.05] and decreased further along with the aggregation of cirrhosis (P <
      0.05). CONCLUSION: The expression of growth hormone receptor in human cirrhotic
      liver cells is downregulated. The more severe liver cirrhosis the more the
      downregulation. The decreased expression of growth hormone receptor mRNA may
      account for the downregulated expression of growth hormone receptor in cirrhotic
      liver tissues.

PMID- 11953153
TI  - [Role of the pS(2) in gastric mucosa adaptative cytoprotection from stress].
AB  - OBJECTIVE: To determine the expression of pS(2) (a member of trefoil peptides) in
      gastric mucosal of rats undergone WRS, and to probe the role of pS(2) in adaptive
      cytoprotection. METHODS: Wistar rats were exposed to single or repeated WRS for 4
      h every other day for up to 6 days. Gastric mucosal blood flow (GMBF) was
      measured by LDF-3 Flowmeter. The degree of the gastric mucosal lesions (UI) was
      evaluated grossly and histologically. The expression of pS(2) was determined by
      RT-PCR and immunohistochemistry. RESULTS: (1) WRS applied once produced numerous
      gastric mucosal erosions. UI gradually declined and GMBF restored on 3 d, 5 d
      after stress. UI was reduced to 20.8% and GMBF increased up to 94.5% of normal
      value. The expression of pS(2) was increased during the healing of stress-induced
      ulceration. The same results were observed by immunohistochemistry (0.50 +/- 0.13
      vs 0.70 +/- 0.11, P < 0.01). (2) With repeated WRS, the adaptative cytoprotection
      against stress was developed. UI after four consecutive WRS was 22% of UI after
      one WRS. GMBF after four consecutive was 94.2% of normal value. Cell
      proliferation in the neck regions of gastric glands was activated. The expression
      of pS(2) was increased by using RT-PCR (0.37 +/- 0.02 vs 0.77 +/- 0.01, P < 0.01)
      and immunohistochemistry (0.55 +/- 0.04 vs 2.46 +/- 0.08, P < 0.01). CONCLUSION:
      Increased expression of pS(2) could play an important role in adaptation of
      gastric mucose developed after repeated WRS.

PMID- 11953154
TI  - [Imaging diagnosis and classification of hepatic cystic echinococcosis].
AB  - OBJECTIVE: To investigate the imaging characteristics of hepatic cystic
      echinococcosis in different imaging examinations and to formulate an imaging
      classification. METHODS: The data of pre-operative imaging examination of 2 039
      cases with hepatic cystic echinococcosis, who underwent operation during the
      period January 1984 to December 2000, by B mode ultrasonograohy (all cases), X
      ray computed tomography (909 cases), and magnetic resonance imaging (24 cases)
      were analyzed, being compared with the pathological findings of the resected
      specimens. RESULTS: Imaging examinations succeeded to identify not only the
      location, size, and form of hydatid cyst in liver, but also the typical
      pathomorphology of complications. The hepatic echinococcosis can be divided into
      seven imaging-diagnostic patterns: solitary cyst (1 625 cases, 79.70%), multiple
      cysts (414 cases, 20.30%), primary hydatid cyst with daughter cysts (1 114 cases,
      54.63%), calcified cyst (186 cases, 9.12%), consolidated cyst (28 cases, 1.37%),
      cyst with infection (391 cases, 19.18%), and ruptured cyst (298 cases, 14.62%).
      CONCLUSION: A new diagnostic system of hepatic echinococcosis has been formulated
      based on imaging examination and by reference to clinical manifestation. It helps
      select appropriate operation program.

PMID- 11953155
TI  - [Comparison of curative effect for colon flat lesion between mucosa resection and
      fulguration with high frequency current after mucosa staining under magnifying
      endoscope].
AB  - OBJECTIVE: To observe the relationship between the pit patterns and pathology and
      compare the curative effect for colon flat lesion between endoscopic mucosa
      resection (EMR) and fulguration with high frequency current (FHFC). METHODS: They
      were divided to two groups. There were 37 cases for FHFC in group A, and 34 cases
      for EMR in Group B. The two groups were comparabal. Examining patients suffering
      with colon flat lesions with magnifying endoscope and observing the pit patterns
      of mucosa after staining with indicarmine. RESULTS: The pit patterns of
      inflammatory or hyperplastic lesions were mainly pit II, adenoma pit III and pit
      IV, and carcinomatous lesions pit IV and pit V. The worse the differentiation
      degree of lesions was, the higher the pit patterns were. There were no difference
      (P > 0.05) between group A and B in complication and quantity, classification and
      distribution of lesions. No canceration was detected in 21 cases with adenoma in
      group A, while 4 cases of canceration (all were adenocacinoma) was found in 20
      cases whith adenoma in group B. There was significance in canceration between two
      groups (P < 0.05). CONCLUSIONS: The worse the differentiation degree of lesions
      was, the higher pit patterns were. EMR and FHFC share the same validity and
      security when treating the flat lesions, but by EMR, doctors could judge whether
      the lesions were resected completely, once the remained lesions were found, they
      could be resected immediately again lesion in case of omission of canceration.

PMID- 11953156
TI  - [Pulmonary function in infants with respiratory syncytial virus bronchiolitis].
AB  - OBJECTIVE: To observe the dynamics of pulmonary function in infants with
      respiratory syncytial virus (RSV) bronchiolitis. METHODS: The to test the
      pulmonary function of 31 infants with RSV bronchiolitis during acute phase at
      admission was tested. Pulmonary fuction test was performed for the second time
      among 17 out of the 31 infants during the clinical recovery phase, and performed
      for the third time among 10 out of the 17 infants one week after discharge. In
      the meantime pulmonary function test was performed in 74 healthy infants as
      controls. RESULTS: During the acute phase of RSV bronchiolitis, the respiratory
      rate (RR), peak tidal expiratory flow (PTEF), peak tidal flow/tidal volume
      (PF/Ve), respiratory system resistance (Rrs), and functional residual capacity
      per kilogram (FRC/kg) were significantly increased, while the inspiratory tidal
      volume (Vi), inspiratory volume per kilogram (Vi/kg), expiratory tidal volume
      (Ve), percent of tidal volume to peak tidal expiratory flow (%V-PF), terminal
      flows/peak expiratory flow (25/PF), respiratory system compliance (Crs), and
      respiratory system compliance per kilogram (Crs/kg) were significantly decreased
      as compared with those in healthy infants. Ratio of mid-expiratory to mid
      inspiratory flow (ME/MI) and respiratory system time constant (Trs) showed no
      statistically significant differences. The tidal breathing flow-volume (TBFV)
      loop displayed a concave expiratory curve. During the clinical recovery phase,
      the above abnormal indexes showed significant improvement, except for the %V-PF,
      25/PF and Crs/kg which were still lower as compared with those in healthy
      infants, most indexes had returned to normal. The TBFV loop showed mild
      decelerating expiratory limb. One week after discharge all of the indexes
      returned to normal. CONCLUSION: In the acute phase of RSV bronchiolitis higher
      resistance in small airway and obstructive ventilatory disturbance can be seen.
      Some of the indexes remain abnormal during the clinical recovery phase. However,
      the abnormalities disappear in a short time. Pulmonary function test is a
      valuable way for surveillance of the course and prognosis of RSV bronchiolitis.
      %V-PF, 25/PF, and FRC/kg are sensitive indexes.

PMID- 11953157
TI  - [Idiopathic retroperitoneal fibrosis: a clinical analysis of 7 cases].
AB  - OBJECTIVE: To investigate the clinical characteristics of idiopathic
      retroperitoneal fibrosis. METHODS: The clinical manifestations, laboratory
      examination, and CT and MIR features of seven patients with idiopathic
      retroperitoneal fibrosis were analyzed. RESULTS: (1) The initial symptoms were
      nonspecific and variable and included abdominal pain, low back pain, and weigh
      loss. Later symptoms, depending on the organs affected, included abdominal mass,
      ascites, urinary symptoms, and and intestinal obstruction. (2) Diagnosis of IRF
      could be based on elevated erythrocyte sedimentation rate and gamma globulin and
      positive findings by CT and MIR. For masses in retroperitoneal space and adhesion
      of abdominal organs, CT was more sensitive than B mode ultrasonography. However,
      for hydronephrosis and lesions in ureter, B mode ultrasonography was the first
      choice. (3) Steroid and immunosuppressant were effective during the early stage
      of IRF. In the advanced stage, operation was necessary. CONCLUSION: Imaging
      examination is important for diagnosis of IRF. However, the final diagnosis
      depends on pathological examination. Treatment depends on the stage of disease.
      The prognosis is optimistic.

PMID- 11953158
TI  - [Serum levels of soluble intercellular molecule 1 (sICAM-1) in endometriosis].
AB  - OBJECTIVE: To investigate the serum levels of ICAM-1 and its relationship to the
      extent of the disease. METHODS: Serum sICAM-1 levels of 21 women with
      endometriosis were measured with a specific enzyme-linked immunosorbent assay,
      and 21 women without endometriosis were selected as control. Serum sICAM-1 levels
      were compared between endometriotic and non-endometriotic women, and among
      patients at different stages of endometriosis. RESULTS: Significantly higher
      serum sICAM-1 levels were observed in women with endometriosis [(0.30 +/- 0.07)
      microgram/ml] than in those without endometriosis [(0.18 +/- 0.05) microgram/ml]
      (P < 0.01); in women with stage I approximately II of endometriosis, the serum
      sICAM-1 levels were (0.24 +/- 0.06) microgram/ml, while in those with stage III
      approximately IV of endometriosis, the serum sICAM-1 level was (0.32 +/- 0.06)
      microgram/ml, the difference is of statistically significant.No differences of
      serum sICAM-1 level was found between proliferative and secretary phase in women
      with and without endometriosis. CONCLUSIONS: Significantly elevated serum sICAM-1
      levels in women with endometriosis, especially in those with advanced stages of
      the disease suggests the molecule might be of value in pathogenesis of
      endometriosis.

PMID- 11953159
TI  - [Repair of meniscal defects with autologous tissue-engineered fibrocartilage].
AB  - OBJECTIVE: To repair critical-sized meniscal defects in an immunocompetent mammal
      by tissue engineering approach. METHODS: 15 45-day-old Changfeng crossbred pigs
      were selected as experimental animals. Autologous fibrochondrocytes were obtained
      from left knee menisci by modified Klagsbrun's method and were proliferated in
      vitro to a proper amount. A 1-cm-long full-layer defect of right medial meniscus
      was created anterior to the medial collateral ligament. PGA-fibrochondrocyte
      Pluronic complex, fibrochondrocyte-Pluronic complex or PGA only was respectively
      implanted into the defects. We used intact menisci and untreated meniscal defects
      as controls. Samples respectively obtained in 9 w, 16 w and 25 w were appraised
      by general observation, histology, biochemistry and biomechanics. RESULTS: From
      the sights of general morphology, histological structure and Young's Modulus
      (59.7% of that in normal meniscus at 25 w), the PGA-cell-Pluronic complex can
      form the best quality tissue, which can stabilize the GAG ratio (74.5% of that in
      normal cartilage at 25 w) of femoral entocondyle cartilage. CONCLUSION:
      Autologous tissue-engineered fibrocartilage is a promising feasible method to
      regenerate or reconstruct menisci so as to hold back the degenerative changes of
      the knee.

PMID- 11953160
TI  - [The vasodilation mechanisms of human erythrocyte-derived depressing factor].
AB  - OBJECTIVE: To evaluate the effect of EDDF a new erythrocyte-derived depressing
      factor, on the NO/cGMP pathway in aorta of normal rats and rat, with hypertension
      induced by L-NNA. METHODS: Thirty male Wistar rats aged 10 weeks were divided
      into two groups: L-NNA group and control group, 15 rats for each group. L-N(G)
      nitro-arginine (L-NNA) was injected into the abdominal cavity of the rats in the
      L-NNA group at dose of 15 mg/kg twice a day for four weeks. Normal saline was
      injected the same way in the control group. The levels of cGMP in aorta and
      plasma were measured by radioimmunoassay and (3)H-L-arg incorporation. NOS was
      measured by immunohistochemistry. RESULTS: One day after injection of L-arg, the
      blood pressure of the experimental rats began to rise remarkably (18.8 kPa vs
      16.4 kPa, P < 0.05), and then remained at a high level. The L-arg. transfer rate
      (pmol small middle dotmg(-1) small middle dotpr small middle dotmin(-1)) of aorta
      in L-NNA group was significantly lower than that of control group (13.0 +/- 0.9
      vs 16.8 +/- 1.2 P < 0.05). After incubation with EDDF (10(-4) g/ml), the L-arg
      transfer rate and cGMP level of aorta were remarkably increased in normal rats
      (20.1 +/- 0.9 vs 16.8 +/- 1.2, P < 0.05 and 233 +/- 14 vs 187 +/- 10, P < 0.05).
      The L-arg transfer rate and cGMP level of aorta remained unchanged afeter
      incubation with EDDF in the L-NNA group (13.0 +/- 0.9 vs 13.2 +/- 0.3 and 148 +/-
      16 vs 186 +/- 12). The cGMP level (pmol/g) of aorta in L-NNA group were obviously
      lower than that of control rats (148 +/- 16 vs 186 +/- 12, P < 0.05).
      Immunohistological staining of NOS in aorta was obviously lighter in L-NNA group
      than in control group. The immunohistochemical staining intensity in aorta
      remained the same after incubation with EDDF in L-NNA group. CONCLUSION: The
      NO/cGMP pathway might be in charge of vasodilation mechanism of EDDF.

PMID- 11953161
TI  - [Synthesis and expression of 42 kD C-terminal region of the major merozoite
      surface protein (MSP1 - 42) of P. falciparum 3D7 strain in pichia pastoris].
AB  - OBJECTIVE: Production of 3D7/MSP1 - 42 recombinant protein with correct
      conformation in Pichia pastoris for vaccine efficiency assay. METHODS: Asymmetric
      PCR-based method was utilized to synthesize the 1 202 bp 3D7/msp1 - 42 gene. The
      expressing plasmid containing the synthetic gene was introduced into Pichia
      pastoris by electroporation. The secreted product was detected by Western Blot.
      RESULTS: The redesigned entire 3D7/msp1 - 42 gene was generated with error-free,
      and expressed to produce 42 kD recombinant protein in secreted form.
      Conformational monoclonal antibody specific for MSP1 C-terminal can interact with
      the recombinant protein. CONCLUSION: The redesigned 3D7/msp1 - 42 gene was
      expressed in P. pastoris with full length of recombinant protein which resembled
      most likely to the native protein.

PMID- 11953162
TI  - [Effect of immunomagnetic selection in purging autologous peripheral blood
      progenitor cell of breast cancer patients].
AB  - OBJECTIVE: To evaluate the effect of immunomagnetic technique in purging of
      peripheral blood progenitor cell (PBPC) of breast cancer patients. METHODS: A
      sample of APBSC from non-breast cancer patients mixed with 1% MCF-7 cell lines
      and 10 samples of APBSC from breast cancer patients were subjected to positive
      purging, negative purging, and positive/positive purging. The CD34 + cell purity,
      CD34 + cell recovery rate and the enrichment of colony form units were compared.
      The number of tumor cells before and after immunochemistry (ICC) and flow
      detected purging procedure cytometry (FCM). The influence of refrigeration on the
      effect of purging was analyzed. RESULTS: The TC depletion in 10 samples of PBPC
      of breast cancer patients after positive purging was 2.1 (1.1 approximately 2.7)
      log steps, the CD34 + cell purity was 55.1 (25.9 approximately 99.5)%, and the
      CD34 + cell recovery was 39.4 (34.0 approximately 80.0)%. After the 6 samples of
      ICC positive PBPC from breast cancer patients were subjected to negative
      selection and subsequent positive purging, the mean CD34 cell purity was 64.3
      (34.0 approximately 86.4)%, the mean CD34 + cell recovery was 35.0 (24.0
      approximately 52.5)%, the purging efficiency was 3.0 (1.8 approximately 3.9) log,
      and the enrichment of colony-forming units-granulocyte macrophage (CFU-GM) and
      burst-forming unit-erythrocyte (BFU-E) were 2.2 and 3.1 respectively. TCs were
      detectable in all 6 cases prior to the purging procedure by ICC and FCM. After
      the -/+ purging procedure, only one case was tumor cell positive by ICC and
      residual tumor cells could be detected by FCM, however the number of TCs was
      evidently decreased. Along with the extension of refrigeration time, the CD34
      cell purity, CD34 cell recovery, and tumor cell clearance rate decreased.
      CONCLUSION: Immunomagnetic double negative/positive selections an effective,
      rapid and simple purging method.

PMID- 11953163
TI  - [Promotion of growth of human breast cancer cells MDA231 by human sperm membrane
      bound hyaluronidase: an experimental study].
AB  - OBJECTIVE: To study the mechanism how human sperm membrane-bound hyaluronidase
      (PH20) promotes the gowth of human breast cancer. METHODS: Full-length cDNA of
      human PH20 was transfected into human breast cancer cell line MDA231. The
      transfectant MDA231-PH20 was then implanted into the chorio-allantoic membrane
      (CAM) of chicken embryo to form a tumor. Four days after implantation, the tumors
      were resected to be weighed. The angiogenesis in tumor tissue was examined by
      immunohistochemistry. Trans-well cell culture was used to study the effect of
      MDA231-PH20 on the growth of adult bovine aortic endothelial cells (ABAE). The
      expression of fibroblast growth factor-2 (FGF-2) in the tumor cells was
      investigated by Western blotting. ELISA was used to examine the secretion of FGF
      2 and hyaluronic acid. The same amount of empty vector pcDNA3, instead of PH20,
      was transfected into human breast cancer cell line MDA231 as control group.
      RESULTS: The average weight of tumor four days after implantation was 44.7 mg +/-
      10.2 mg in the MDA231-PH20 group, and was 21.3 mg +/- 2.8 mg in the control group
      (t = 2.418, P = 0.038). Neogenetic vessels increased remarkably in MDA231-PH20
      tumor tissues. The expression of FGF-2 protein was much higher in MDA231-PH20
      cells. The FGF content and HA secretion were higher in the MDA231-PH20 group than
      in the control group (8.10 pg/ml +/- 1.56 pg/ml vs. 3.94 pg/ml +/- 0.82 pg/ml,
      and 1 220 ng/ml +/- 254 ng/ml vs. 462 ng/ml +/- 96 ng/ml, all P < 0.01). The
      growth of ABAE cells was significantly accelerated after co-culture with MDA231
      PH20 transfectant. CONCLUSION: PH20 may promote the growth of human breast cancer
      by accelerating the release of FGF-2 from tumor cells, decomposing HA into small
      fragments, and promoting angiogenesis.

PMID- 11953164
TI  - [Neuronavigator-guided microsurgery for resection of brain tumors].
AB  - OBJECTIVE: To study locating accuracy for the brain tumors and their peri
      structures by the neuronavigator and elucidate the microsurgical effects.
      METHODS: 65 patients with intracranial tumors were microsurgically treated by the
      application of Stealth Station and Vector Vision system. The treatment effects
      were summarized and the neuronavigational accuracy was discussed. RESULTS: After
      mean fiducial error (MFE) and sustained accuracy (SA) were satisfied. Total tumor
      removal was achieved in 63 cases (97.0%), subtotal removal in 2 cases (3.0%). The
      neurological functions were improved in 56 cases (86.2%), unchanged obviously in
      9 cases (13.8%). No case deteriorated and died in the group. CONCLUSIONS:
      Navigation systems are reliable and accurate in making microneurosurgical plans
      for brain tumors. And they can provide tracing of the tumor in the operation and
      guide the operator's manipulation. The techniques, which help total removal of
      the tumors and reduce the postoperative complications, are very useful in
      guarantee operation effects.

PMID- 11953165
TI  - [Image-guided microsurgery in resection of intracranial cavernous hemangioma].
AB  - OBJECTIVE: To study the methods and effectiveness of image-guided microsurgery in
      resection of intracranial cavernous hemangioma. METHODS: Between July 1997 and
      January 2001, 44 patients with intracranial cavernous hemangioma, 27 males and 17
      females with a mean age of 35 years, among which 5 cases had multiple lesions,
      underwent image-guided microsurgery. The locations of lesions included frontal
      lobe (n = 14), temporal lobe (n = 12), parietal lobe (n = 6), cerebellum (n = 6),
      thalamus (n = 5), pons (n = 5), and orbital lobe (n = 1). A small silicon
      catheter, used as a guider, was implanted to the deep-seated lesion (except the
      brain stem lesions) before excision of the lesion in order to prevent brain
      shift. RESULTS: Total removal of the lesions was achieved in all patients without
      operational death. Follow-up revealed marked improvement of symptoms in 26 case
      and no change of symptom(s) in 13 cases. 5 cases suffered from additional
      neurological deficits, mainly exacerbation of hemiparalysis and aphasia, the
      condition of two of which, however, gradually improved within the period of
      follow-up. No residue of lesion and relapse were found during follow up.
      CONCLUSION: With the assistance of the image-guided surgical system, functional
      area can be effectively avoided, and surgical injury can be decreased. It is well
      suited for accurate localization and safe resection of small, deep-seated
      cavernous malformations.

PMID- 11953166
TI  - [Stereotactic biopsy for intracranial deep lesions].
AB  - OBJECTIVE: To investigate the histological diagnostic efficacy and accuracy of
      stereotactic biopsy for intracranial deep lesions under computerized tomography
      (CT) and magnetic resonance imaging (MRI) guidance. METHODS: CT or MRI-guided
      stereotactic biopsy was performed in 605 cases with intracranial deep lesions.
      All the procedures were done under local anesthesia with Leksell stereotactic
      system. CT or MRI film was used to determine the coordinate in 450 cases and the
      computer-assisted planning for neurosurgery (CAPN) in 155 cases. RESULTS: Brain
      tumors, inflammatory lesions, and abnormal but nonspecific lesions were diagnosed
      pathologically in 537 cases (88.75%), 30 cases (4.96%), and 13 cases (2.15%)
      respectively. In 20 cases (3.31%) the biopsy procedure failed to provide useful
      pathological evidence. The total positive rate of biopsy was 96.69%.
      Complications associated with biopsy occurred in 18 patients (2.98%), and 2
      patients (0.33%) died following the procedure. CONCLUSION: Stereotactic biopsy
      using MRI-guided stereotactic approach or CT-guided technique is a safe and
      reliable method for histological diagnosis of intracranial deep lesions.

PMID- 11953167
TI  - [Level of plasma lysophosphatidic acid in patients with cerebral ischemic attack,
      a preliminary study].
AB  - OBJECTIVE: To study the level of plasma lysophosphatidic acid (LPA) in patients
      with TIA, cerebral thrombosis or possible ischemic attack. METHODS: Phospholipid
      was extracted from plasma of patients with TIA, cerebral thrombosis or possible
      ischemic attack by organic solvent. Lysophosphatidic acid was isolated further.
      The quantity of LPA was determined by assaying its phosphorous component.
      RESULTS: LPA level of patients with TIA, cerebral thrombosis or possible ischemic
      attack were 2.14 +/- 1.02, 1.50 +/- 0.85, and 1.73 +/- 1.14 micromol/L blood
      plasma respectively, all significantly higher than that in control group (1.00 +/
      0.70 micromol/L, P < 0.05). The plasma LPA level decreased after anticoagulant
      treatment. CONCLUSION: As a molecular marker released by activated platelets in
      vivo, plasma PLA may be valuable in diagnosis of cerebral ischemic attack.

PMID- 11953168
TI  - [The protective mechanism of fructose-1, 6-diphosphate on ischemic brain injury].
AB  - OBJECTIVE: To explore the protective mechanism of fructose-1, 6-diphosphate (FDP)
      on ischemic brain injury. METHODS: A model of permanent focal cerebral ischemia
      was performed in rats by intraluminal filament occlusion of middle cerebral
      artery. TTC staining, immunohistochemistry, Western blotting, and TUNEL staining
      were used to evaluate the effect of FDP on infarct area, apurinic/apyrimidinic
      endonuclease (APE/Ref-1) expression, and apoptosis in ischemic brain tissue.
      RESULT: The infarct areas of FDP intervening group and ischemia for 24 h group
      were 31.0 +/- 2.9 mm(2) and 47.3 +/- 6.0 mm(2) respectively. The numbers of TUNEL
      positive cells in ischemic penumbra were 69.3 +/- 2.4/mm(2) and 42.8 +/-
      1.7/mm(2) in FDP group and ischemia for 24 h group respectively. FDP upregulated
      the expression of APE/Ref-1 protein in ischemic penumbra. The numbers of APE/Ref
      1 immuno-positive cells in the ischemia for 24 h group and FDP group were 47 +/-
      3.4/mm(2) and 26.3 +/- 2.9/mm(2) respectively. The values of optical density by
      Western blotting in these two groups were 5.3 +/- 3.2 and 13.8 +/- 5.4
      respectively. The differences between these two groups were statistically
      significant. CONCLUSION: Through upregulating the expression of APE/Ref-1
      protein, FDP improves the repair ability of brain tissue in the course of
      ischemic injury and mitigated the quantity of apoptosis in penumbra, thus
      preventing the extension of cerebral infarction.

PMID- 11953169
TI  - [Relationship between apolipoprotein H and lipid in stroke patients].
AB  - OBJECTIVE: To study the correlation of serum apolipoprotein H (ApoH) with blood
      lipids and the relationship between ApoH and stroke. METHODS: The serum levels of
      ApoH of 33 patients with acute cerebral infarction (ACI), 18 patients with acute
      cerebral hemorrhage (ACH), 17 patients with cerebral apoplexy and family history,
      and 33 healthy control were measured by radioimmunoassay. The blood lipids of the
      above mentioned subjects were measured by enzymological methods. RESULTS: The
      serum ApoH levels in acute cerebral infarction (ACI) patients, acute cerebral
      hemorrhage (ACH) patients, and healthy controls were 288 +/- 85 mg/L, 248 +/- 68
      mg/L, and 256 +/- 71 mg/L respectively. There was a significant correlation
      between serum ApoH and total CHO and between ApoH and LDL in ACI patients (r =
      0.394, P < 0.05; r = 0.394, P < 0.05). However, no correlation between ApoH and
      triglyceride was found. In 17 cases of cerebral apoplexy with familial history,
      the serum ApoH was correlated with HDL. CONCLUSION: Serum ApoH is correlated with
      CHO and LDL in ACI patients. No such correlation can be found in healthy persons
      and ACH patients.

PMID- 11953170
TI  - [Effect of selective cyclooxygenase -2 inhibitor on the renal lesion of
      streptozotocin-induced diabetic rats and its possible mechanism].
AB  - OBJECTIVE: To investigate the effect of selective cyclooxygenase (COX)2 inhibitor
      meloxicam on the renal lesion of diabetic rats and its possible mechanism.
      METHODS: Twenty-nine rats were randomly divided into four groups: normal control
      rats (n = 6), streptozotocin (STZ)-induced diabetic rats without treatment (n =
      8), STZ-induced diabetic rats treated with indomethacin (2 mg x kg(-1) x d(-1))
      (n = 6), and STZ-induced diabetic rats treated with meloxicam (2 mg x kg(-1) x d(
      1)) (n = 9). Sixteen weeks later, the blood sugar, blood urea nitrogen (BUN), and
      blood creatinine were examined. Radioimmunoassay was used to examine the
      prostaglandin(2) (PGE(2)) and Thromboxane B(2) (TXB(2)) in the urine. The
      expression of transforming growth factor -beta1 (TGF-beta1) and TGF-beta receptor
      type II (TbetaR2) of the renal cortex were measured by reverse transcription
      polymerase chain reaction (RT-PCR) analysis. Immuno-precipitation analysis was
      carried out to examine the protein level of angiotensin II type 1 (AT1) receptor.
      Periodic acid-Schiff staining was used to examine the morphological changes by
      light microscopy. RESULTS: In the STZ-induced diabetic group, the blood levels of
      sugar, BUN, and creatinine were higher, and the creatinine clearance (Ccr) was
      remarkably higher in comparison with those in the normal control group (P <
      0.05). Ccr was lower in diabetic rats treated with indomethacin and diabetic rats
      treated with meloxicam than in diabetic rats without treatment (P < 0.05). There
      was no difference of blood creatinie among these three groups. The blood sugar
      level in diabetic rats treated with meloxicam was lower than those in the
      diabetic rats treated with indomethacin and untreated group (all P < 0.05). The
      renal weight/body weight ratio was significantly higher in the untreated group
      than that in the control group. The PGE(2), TXB(2) and albumin levels in urine of
      STZ-induced diabetic rats were 1,641 +/- 288 pg/24 h 5,507 +/- 1,359 pg/24 h, and
      46.3 +/- 9.5 microg/24 h respectively, much higher than those in meloxicam group
      (910 +/- 255 pg/24 h, 3,272 pg/24 h +/- 670 pg/24 h and 17.2 +/- 5.4 microg/24h
      respectively, all P < 0.01). The urine PGE(2) and albumin was 1,195 +/- 448 pg/24
      h and 34.1 +/- 10.2 microg/24 h respectively in the indomethacin group. There was
      no difference in renal weight/body weight ratio and TXB(2) excretion between the
      untreated group and indomethacin group. The relative contents of TGF-beta1 and
      TbetaR2 mRNA expression in renal cortex of STZ-induced diabetic rats were 0.185
      +/- 0.037 and 0.194 +/- 0.054, much higher than those in other groups. Glomerular
      hypertrophy, mesengial expansion, extracellular matrix accumulation, and
      sclerosis of partial glomeruli were seen in diabetic rats without treatment and
      those treated with indomethacin. The pathological changes were less in meloxicam
      group (P < 0.05). CONCLUSION: The selective COX-2 inhibitor meloxicam
      significantly suppresses TGF-beta1 and TbetaR2 genes expression, elevates the
      protein level of AT1 receptor and attenuate the renal lesion caused by diabetes.
      TGF-beta1 and AT1 receptor may be involved in the mechanism concerned.

PMID- 11953172
TI  - [Localization diagnosis of chyluria by radionuclide lymphoscintigraphy].
AB  - OBJECTIVE: To study the effect of radionuclide lymphoscintigraphy, a new method
      of localization diagnosis of chyluria. METHODS: Radionuclide lymphoscintigraphy
      was used to examine 34 patients with chyluria and the results of radionuclide
      lymphoscintigraphy was compared with those of cystoscopy and lymphangiography.
      RESULTS: Among the 34 patients 85.3% of unilateral localization diagnosis by
      radionuclide lymphoscintigraphy was coincident with that by cystoscopy. The
      positive rate of bilateral localization diagnosis was higher than that by
      cystoscopy. CONCLUSION: A less invasive technique, radionuclide
      lymphoscintigraphy can be used as a new option for the localization diagnosis of
      chyluria.

PMID- 11953171
TI  - [Treatment of xerophthalmia by transplantation of autologous vascularized
      submandibular gland].
AB  - OBJECTIVE: To investigate the feasibility of treatment of xerophthalmia by
      transplantation of autologous vascularized submandibular gland (SMG). METHODS:
      The SMGs of 19 patients with severe keratoconjunctivitis were transferred to
      their temporal region by microsurgery. The arteries and veins of the SMGs were
      anastomosed to the super-temporal arteries and veins, the SMG ducts were
      implanted into the conjunctival fornix of the eye. The saliva secreted by the SMG
      was used as the substitute of tear. RESULTS: The transplantation succeeded in 14
      patients and failed in 4. Follow up lastred for 3 months to 2 years. The symptom
      of corneal xerosis disappeared, the symptoms of photophobia and anemophobia were
      alleviated, and artificial tear substitutes were not used any more. Epiphora
      appeared in 4 cases and disappeared after partial resection of the transplanted
      gland. Atresia of orifice occurred in one case and was cured by reconstruction of
      the duct. CONCLUSION: Transplantation of autologous vascularized SMG is effective
      in treating severe keratoconjunctivitis sicca.

PMID- 11953173
TI  - [Imaging diagnosis of hepatic alveolar echinococcosis].
AB  - OBJECTIVE: To study the characteristics of hepatic alveolar echinococcosis in B
      mode ultrasonography (BU), computerized tomography (CT), and magnetic resonance
      imaging (MRI) so as to increase the pre-operative diagnostic rate. METHODS: The
      data of forty-six cases with hepatic alveolar echinococcosis who underwent
      operation during the period January 1984 to December 2000 were analyzed and
      compared with the pathological findings of the resected specimens. All of the
      cases were examined by BU and CT, and 12 of them were examined by MIR. RESULTS:
      The imaging characteristics of the 46 cases were divided into three types:
      infiltration (41 cases, 89.1%), calcification (39 cases, 84.8%), and cavity with
      liqueficaction (37 cases, 80.4%). Nine imaging signs were found to be specific to
      hepatic alveolar echinococcosis and of diagnostic significance: halo belt sign,
      calcification sign, annual ring sign, invacuation sign, cavity with
      liqueficaction sign, grotto sign, peninsula sign, alveolar sign. With these
      signs, the diagnostic accuracy rate reached 97.7% in this series. CONCLUSION:
      There are nine imaging diagnostic signs specific to hepatic alveolar
      echinococcosis. They help detect the location, pathology of this disease and
      determine operation program. Identification of only one of them is adequate for
      diagnosis of hepatic alveolar echinococcosis.

PMID- 11953174
TI  - [Feasibility of using hepatitis B virus surface antigen as target antigen in
      immunogen therapy against cancer].
AB  - OBJECTIVE: To investigate the feasibility of using hepatitis B virus surface
      antigen (HbsAg) as a tumor-associated antigen in immunogen therapy against tumor.
      METHODS: (1) Dendritic cells (DCs) were extracted from bone marrow of mice and
      cultured. Mature DCs were transfected with adenovirus vector highly expressing
      HBsAg and enhanced green fluorescence protein (EGFP) (DC-HBsAg). Eight C57BL/6J
      mice were immunized by intravenous injection of 1 x 10(6) DC-HBsAg. Seven days
      after, the immunization procedure was boosted by injection of the DC-HBsAg with
      the same dosage once more. Another eighteen mice were divided into 3 groups, 6 in
      each, to be injected with DC-EGFP (DCs transfected with 1 x 10(6) adenovector
      expressing only EGFP), 1 x 10(6) DCs, and PBS of the same volume as controls. One
      week after the second injection, subcutaneous injection of 7X105 mouse melanoma
      cells B16 or B16-HBsAg (B16 cells expressing HBsAg) was performed to each mouse.
      The size of tumor was measured every 2 - 3 days. When the tumor grew to the size
      of 2cm or caused ulcer the tumor-carrying mice were killed. The mice in the DC
      HBsAg group that showed no tumorigenesis 30 days after inoculation of B16-HBsAg
      were re-inoculated with 7X105 B16-HBsAg. Three normal B6 mice of the same age and
      sex were used as controls. (2) Other patch of mice were divided into 4 groups and
      injected with DC-HBsAg, DC-EGFP, HBsAg (1 ug/mouse), and PBS in the same way as
      mentioned above. One week after the second injection at least 5 mice in each
      group were inoculated with 7X105 B16-HBsAg and 2 mice in each group were killed
      to have their serum anti-HbsAg titers examined. RESULTS: (1) Seven days after
      inoculation of B16-HbsAg tumor began to grow in all mice in the three control
      groups. Tumor was found in 5 of the 8 mice in the DC-HBsA group and the other 3
      mice in this group remained free of tumor. However, the size of tumor in these 5
      mice was significantly smaller than thate in other groups (P < 0.01). B16-HBsAg
      was re-inoculated to the three mice that showed no tumor growth 30 days after the
      first inoculation of B16-HBsAg. However, still no tumor could be found in them.
      After inoculation of wild type melanoma cell B16 tumorigenesis was seen in the
      two immunization groups. (2) The titer of anti-HBsAg antibody induced by DC-HBsAg
      was obviously lower than that induced by recombinant HBsAg vaccine. However, the
      size of tumor in HBsAg group was obviously smaller than that in recombinant HBsAg
      group. CONCLUSION: DC-HBsAg induces HBsAg-specific antitumor effect, stronger
      than that induced by recombinant HBsAg vaccine although the humoral immune
      response elicited by DC vaccine is much weaker that that induced by recombinant
      HBsAg vaccine. HBsAg can be used as a target antigen in immunogen therapy for
      treatment of cancer.

PMID- 11953175
TI  - [Expression of TTF-1 in thyroid tumors originating from follicular epithelium and
      its correlation with expression of RET, galectin-3 and mucin-1 genes].
AB  - OBJECTIVE: To explore the expression of thyroid transcription factor-1 (TTF-1) in
      thyroid tumors and in different parts of follicular epithelium and the
      correlation of expression of TTF-1 with the expression of RET, galectin-3 (Gal-3)
      and mucin-1 (MUC1) genes. METHODS: One hundred thirty-three samples of resected
      thyroid tumors were examined by streptavidin/peroxidase (S-P) immunohistochemical
      technique to detect the expression of TTF-1 and RET, Gal-3, and MUC1 genes.
      RESULTS: (1) TTF-1 was expressed in the nuclei and cytoplasm of different kinds
      of tumor cells and normal cells around the tumors. There was no significant
      difference between the expression of TTF-1 in nuclei of malignant thyroid tumor
      cells and that in nuclei of benign thyroid tumor cells (P > 0.05). The positive
      expression rate of TTF-1 was 27.40% in cytoplasm of benign tumor and was 66.10%
      in cytoplasm of malignant tumor was 66.10% (P < 0.05). (2) The expression rate of
      RET gene was 38.9% in thyroid adenoma, 88.4% in papillary carcinoma, and 87.5% in
      follicular carcinoma. The difference of expression rate of RET gene between
      adenoma and both of papillary and follicular carcinomas was statistically
      significant (P < 0.05). (3) The expression rate of MUC1 was 23.3% in benign tumor
      and 50.9% in malignant tumor. The expression rate of MUC1 was lower in benign
      thyroid diseases (nodular goiter and adenoma) than in thyroid papillary carcinoma
      and follicular carcinoma (P < 0.05). (4) The expression rate of Gal-3 gene was
      38.4% in benign tumor and 88.1% in malignant tumor. (5) The expression rates of
      Gal-3 and MUC1 in benign lesions (nodular goiter and adenoma) were lower than
      those in thyroid papillary and follicular carcinomas (P < 0.05). The expression
      of Gal-3 and that of MUC1 in thyroid carcinomas were fundamentally parallel.
      However, the sensitivity of Gal-3 was higher than that of MUC1. In part of
      adenomas Gal-1 and MUC1 were positive locally simultaneously. The expression of
      TTF-1 in cytoplasm was associated with that of Gal-3 and MUC1. CONCLUSION: The
      expression of TTF-1 in nucleus is a phenomenon common to both normal and
      pathological thyroid follicles. Combined tests of RET, Gal-3 and MUC1 may act as
      the diagnostic markers to distinguish benign follicular tumor from malignant
      ones. Expression of TTF-1 in cytoplasm is probably a characteristic of malignant
      phenotypes of thyroid tumors.

PMID- 11953176
TI  - [Telomerase activity in cervical carcinoma and cervical intraepithelial neoplasia
      and its correlation to classification of koilocytosis].
AB  - OBJECTIVE: To investigate the telomerase activity in cervical tissues and
      exfoliated cells in patients with cervical intraepithelial neoplasia (CIN) and
      cervical carcinoma, and to study the correlation between telomerase activity and
      koilocytosis classification and between telomorase activity and human
      papillomavirus (HPV) infection. METHODS: Telomeric repeat amplification protocol
      (TRAP) was used to determine the telomerase activity in cervical tissues and
      exfoliated cells in 24 women with normal cervix, 34 patients with cervitis, 78
      patients with CIN and 16 patients with cervical carcinoma. The patients with CIN
      were classified into 3 subgroups according to the abnormality of cervical cells
      (31 CIN(1) cases, 25 CIN(2) cases and 22 CIN(3) cases). The presence and
      classification of koilocyte in cervical tissues was examined by microscopy with
      double blind method. The telomerase activity in koilocytes of different types was
      investigated. RESULTS: The telomerase positive rate was 16.7% (4/24) in normal
      cervical tissue, 17.6% (6/34) in cervitis tissue, 51.6% (16/31) in CIN(1) tissue,
      72.0% (18/25) in CIN(2) tissue, 86.4% (19/22) in CIN(3) tissue, and 100% (16/16)
      in cervical carcinoma tissue respectively. The telomerase positive rate in CIN
      cases was significantly higher than those in normal cervix and cervitis cases
      (all P < 0.01) and the telomerase positive rate was significantly higher in
      cervical carcinoma than in CIN (P < 0.01). It was also significantly higher in
      CIN(3) than in CIN(1) (P < 0.05), while no significant difference was found in
      the telomerase positive rate between normal cervix and cervitis, CIN(1) and
      CIN(2), and CIN(2) and CIN(3) (P > 0.05). No significant difference of telomerase
      positive rate was found between the cervical tissue and exfoliated cells in the
      same case too (P > 0.05). Koilocytes were found in sixty-four out of the 154
      samples of cervical lesions. Among them koilocytes were found in 54 out of 94
      samples of cervical cancer and CIN tissues (koilocytes of type I in 18 cases and
      type II in 36 cases). The telomerase positive rate was 100% in tissues of CIN and
      cervical carcinoma with type II koilocytosis, significantly higher than that in
      tissues with type I koilocytosis (66.7%, P < 0.05). CONCLUSION: (1) Activation of
      telomerase is closely associated with progression of CIN and cervical carcinoma,
      and telomerase might be a useful marker for cervical carcinoma and CIN. (2)
      Cervical exfoliated cells may be used as the substitute of cervical tissues in
      determining telomerase activity. (3) Activation of telomerase is correlated with
      type II koilocytosis and HPV 16/18 infection.

PMID- 11953177
TI  - [Impact of shear stress on expression of platelet membrane glycoproteins].
AB  - OBJECTIVE: To investigate the mechanism of activation of platelet by shear
      stress. METHODS: Specimens of whole blood were exposed to shear stress of
      different intensity (100, 150, 1,000, and 3,000 s(-1)) by modified cone-and-plate
      rotational viscometer. Then the platelets were stained with fluorescent antibody
      technique by flow cytometry to examine the levels of four kinds of platelet
      membrane glycoproteins: PAC-1, CD62P, GPIb/IX, and GPIIb/IIIa. RESULTS: The
      expression of PAC-1 and CD62P on the surface of unactivated platelets was very
      low, with the rates of 1.7% +/- 1.1% (n = 5) and 0.9% +/- 0.5% (n = 5)
      respectively. When the platelets were exposed to high shear stress, the
      expression of these two kinds of glycoproteins increased. The level of PAC-1
      increased quickly and obviously in a short time, reached the peak value, 73.6% +/
      7.4%, in half a minute after exposure to the shear stress of 3,000 s(-1) and
      decreased soon. The expression rate of CD62P was low when the platelets were
      exposed to low shear stress, and then increased slowly along with the increase of
      shear stress. After exposure to the shear stress of 3,000 s(-1) for 7 minutes,
      the expression rate of CD62P reached 26.4% +/- 3.5%. GPIb/IX and GPIIb/IIIa were
      found to exist on the surface of more than 96.5% - 99.4% of unactivated
      platelets. No significant change of GPIb/IX expression was found at relatively
      low shear stress. When the shear stress increased, the expression rate of GPIb/IX
      increased to an extent in 1 minute, then decreased continually. The fluorescent
      intensity of GPIb/IX was 72.4 +/- 6.7 while unactivated, and decreased to 44.9 +/
      4.9 (n = 5) after exposure to the shear stress of 3,000 s(-1) for 7 minutes. The
      expression of GPIIb/IIIa on surface of unactivated platelets, with fluorescent
      intensity of 98.5 +/- 12.1, began to increase under low intensity of shear
      stress. When the stress increased, GPIIb/IIIa expression increased quickly in a
      short time, and began to decrease in 7 minutes with the fluorescent intensity of
      159.5 +/- 23.6 (n = 5) by then. CONCLUSION: High shear stress causes change of
      expression of platelet membrane glycoproteins. Platelets are activated by high
      shear stress directly and independently, and the activation may be mediated by
      these glycoproteins.

PMID- 11953178
TI  - [Upregulation of vascular endothelial growth factor by peroxide in human colon
      cancer].
AB  - OBJECTIVE: To clarify the possible effect of reactive oxygen species such as
      hydrogen peroxide on progression of human colorectal cancer. METHOD: Human colon
      carcinoma cell lines, L174T and HCT8, were treated with low concentration of
      hydrogen peroxide (10(-5) mol/L, 10(-7) mol/L and 10(-9) mol/L, possessed no
      effect on cancer cell growth) for 24 hours before being co-cultured with human
      endothelial cell line ECV-304. The migration of ECV-304 induced by cancer cells
      was calculated and the expression of vascular endothelial growth factor (VEGF) in
      cancer cells was determined using RT-PCR and ELISA. Dactinomycin (1.5 microg/ml)
      was applied to block the transcription of cancer cell so as to observe the effect
      site of cell. Finally the activity of NF-KappaB of cancer cells was estimated
      using laser scanning cytometry. RESULTS: Exogenous hydrogen peroxide of low
      concentration promoted the migration of endothelial cell induced by colon cancer
      cell. When the concentration of H(2)O(2) was 10(-5) mol/L, the average number of
      migration of endothelial cell induced by LS174T was 202.6 +/- 70.2, higher than
      the value of 154.6 +/- 37.9 when no H(2)O(2) was given (t = 3.4751, P = 0.0083).
      When the concentration of H(2)O(2) was 10(-5) mol/L, the average number of
      migration of endothelial cell induced by HCT8 was 145.4 +/- 65.3, higher than the
      value of 113 +/- 72.7 when no H(2)O(2) was given (t = 4.4183, P = 0.0084). The
      expression of vascular endothelial growth factor in cancer cells was enhanced to
      a certain degree, which could be blocked by Dactinomycin. And the half-time of
      VEGF mRNA was not prolonged by treatment with hydrogen peroxide. The activity of
      NF-KappaB of both colon carcinoma cell lines was at a higher level after being
      treated with hydrogen peroxide for 24 hours. CONCLUSION: Hydrogen peroxide
      increases vascular endothelial growth factor expression in colon cancer cell, and
      it is possible that such reactive oxygen species as hydrogen peroxide facilitates
      development of colon cancer.

PMID- 11953179
TI  - [Autocrine expression of hepatocyte growth factor and its cytoprotective effect
      on hepatocyte poisoning].
AB  - OBJECTIVES: To construct pEGFP-hepatic growth factor (HGF) expression vector,
      detect its transient expression in transfected human hepatocytes, and to
      investigate the influence of autocrine HGF expression on the proliferative
      potential and cytoprotective effects in human hepatocyte. METHODS: Human HGF cDNA
      was ligated to pEGFP vector. The recombinant plasmid was transfected into human
      hepatocyte line QZG with liposome. The expression of HGF protein was observed by
      fluorescence microscopy and immunohistochemistry. Hepatic cells were collected
      24, 48, and 72 hours after transfection to detect the number of [(3)H]-TdR uptake
      in DNA. DNA synthesis was observed by using PCNA stain immunohistochemistry.
      Acute liver cell damage was induced by carbon tetrachloride. The supernatant of
      culture 10 days after transfection of pEGFP-HGF was collected to put in the
      normal culture of hepatic cells. Another sample of supernatant was added with
      anti-HGF antibody to block the HGF activity as control. Cytoprotective effect was
      observed by examining the survival rate of hepatocytes and leakage of
      intracellular alanine transaminase (ALT) and potassium ions. RESULTS: HGF
      identification of pEGFP-HGF by enzyme digestion showed that HGF fragment had been
      cloned into BamH I and Sal I sites of pEGFP-N3. Expression of GFP in transfected
      hepatocytes was observed with fluorescence microscopy. The [(3)H]-TdR uptake
      became 7 times as much as in the control group 96 hours after transfection. After
      HGF transfection, survival rate of hepatocytes poisoned by CCl4 significantly
      increased (83% vs 61%, P < 0.05), and leakage of intracellular alanine
      transaminase and potassium ions decreased (35.16 U x L-1 vs 65.31 U x L-1, P <
      0.01; and 5.59 mmol/L vs 6.02 mmol/L, P < 0.01 respectively). Culture of
      transfected hepatic cells promoted the proliferation of other non-transfected
      cells. This effect was blocked by anti-HGF antibody. CONCLUSION: Transfected HGF
      is expressed in hepatic cells and has the activity of promoting cell division and
      protecting hepatic cells against poisoning.

PMID- 11953180
TI  - [Molecular characteristics of beta-lactamase from Klebsiella pneumoniae].
AB  - OBJECTIVE: To study the molecular characteristics of beta-lactamase from
      Klebsiella pneumoniae. METHODS: Beta-lactamase was prepared from strains of
      Klebsiella pneumoniae isolated clinically for which the minimal inhibitory
      concentration (MIC) of cefoperazone had been >or= 8 mg/L and then was reduced by
      50% by the addition of sulbatam. The isoelectric points of different beta 
      lactamases were examined by LKB2117 Multiphor II Electrophoresis System. The
      molecular weights were examined by polyacrylamide gel electrophoresis. PCR was
      used to detect the TEM-type genes. The PCR products were sequenced by
      chemiluminescence. RESULTS: All four strains of Klebsiella pneumoniae produced
      more than two kinds of beta-lactamase. TEM-type genes were amplified from all
      strains. 97% - 98% of the DNA sequence and amino acid sequence of the TEM-type
      enzymes from 2 strains of Klebsiella pneumoniae were identical with those of TEM
      1 enzyme. The isoelectric points of the beta-lactamases ranged from 5.4 to 9.30
      and the molecular weights were between 23.0 and 43.0 KD. The beta-lactamases from
      Klebsiella pneumoniae 99592 and K. pneumoniae 99607 hydrolysed ceftazidine,
      cefotaxime, and ceftriaxone. The beta-lactamase from K. pneumoniae 99595 had
      stronger activity against ceftazidime, ceftaxime, and ceftriaxone than that from
      K. pneumoniae 99607. CONCLUSION: Klebsiella pneumoniae produces TEM-type extended
      spectrum beta -lactamase against ceftazidine, ceftaxime, and ceftriaxone.

PMID- 11953181
TI  - [Endovascular treatment for abdominal aortic aneurysm, a primary study].
AB  - OBJECTIVE: To summarize the initial experience of endoluminal stent-grafting in
      the treatment of abdominal aortic aneurysm (AAA). METHODS: Stent-graft of proper
      shape and size was selected according to the morphology of AAA and was inserted
      into the lumen of abdominal aortic aneurysm through femoral artery to reconstruct
      the blood flow under X-ray flouroscopy among 34 cases. Data on complications and
      morphological changes were obtained according to a strict follow-up plan.
      RESULTS: The stent-grafting procedure was technically successful in all 34
      patients. None of them required open repair. Five patients (14.7%) suffered from
      primary endoleaks after stent-graft deployment and 1 patient suffered from
      paraplegia and acute graft thrombosis. No other complications (kidney infarction,
      limbs and colon ischemia, etc) were found. The average follow-up time was 21 +/-
      4.7 months. Perioperative death rate was 0% and total death rate was 3%. Two
      cases with primary endoleak developed into lasting endoleak during the follow-up
      period with a rate of late endoleak (> 30 days) of 11.7%. Secondary endoleak was
      found in 2 cases. One case with limb stent disconnection accepted secondary
      intervention. The mean max aneurysm diameter in cases without endoleak decreased
      significantly 6 months to 2 years after operation (P < 0.01). The aneurysm in two
      cases with secondary type I endoleak increased and one of them underwent
      secondary intraluminal treatment. CONCLUSION: Endovascular technique is a
      reliable method of treating AAA with micro-trauma. Endoleak is the main
      complication of this technique. Follow-up is an important component of the
      treatment plan. The aim of endoluminal repair is to completely neglect the
      aneurysmal lumen and prevent the aneurysm from increasing during follow-up.

PMID- 11953183
TI  - [Surgical treatment of aorta-pulmonary window].
AB  - OBJECTIVE: To summarize the experience of surgical treatment of aorta-pulmonary
      window. METHODS: Between January 1980 and August 2000, 18 patients suffering from
      aorta-pulmonary window, 11 males and 7 females, with a mean age of 6.5 years (2
      approximately 14 years), underwent surgical treatment. Eleven cases were type I,
      3 were type II and 4 were type III. Sixteen patients underwent surgical repair
      under cardiopulmonary bypass at moderate hypothermic temperatures. Deep
      hypothermic circulatory arrest was used in 2 of them. Closed surgical ligation
      under cardiopulmonary bypass at normal thermic temperature was performed on 1
      case. External division and ligation under general anesthesia through left thorax
      was performed on 1 case. Thirteen patients underwent surgical repair through the
      anterior wall of aorta. Surgical repair was performed through the anterior wall
      of pulmonary artery in 3 cases. Other associated malformations were repaired
      simultaneously. RESULTS: Three patients died during the peri-operative period.
      Fifteen patients who survived the operation were followed up for 108 months on
      average. One patient was noted to have residue shunt on aorta pulmonary window.
      The other patients showed alleviation of symptoms and improvement of life
      quality. CONCLUSION: Early diagnosis, suitable surgical procedure and prevention
      and treatment of postoperative complications are the key factors for treatment of
      aorta pulmonary window.

PMID- 11953182
TI  - [Clinical effect of femoral cannulation via artificial vessel in operation for
      aortic dissection].
AB  - OBJECTIVE: To evaluate the effect of femoral cannulation via artificial vessel in
      operation for aortic dissection. METHODS: Operation through femoral cannulation
      via artificial vessel was performed upon 159 patients with aortic dissection, 89
      of Stanford type A and 70 of Stanford type B. An artificial vessel was
      anastomosed end-to-side to the femural artery. Femoral catheter was inserted via
      this artificial vessel. Cardiopulmonary bypass was performed in 90 patients,
      among which 31 had deep hypothermic circulatory arrest. Left heart bypass was
      performed in 69 patients. RESULTS: False lumen perfusion was detected during
      cardiopulmonary bypass in 7 patients (4.4%). Cerebral events occurred in 7
      patients (two patients with diffused cerebral anoxia with one death, and five
      patients with cerebral embolism with three deaths). 12 patients suffered from
      prolonged incision recovery (9.0%), and two from local infection (1.5%). No lower
      extremity ischemia or femoral thrombosis was found in the cannulation side.
      CONCLUSION: Femoral cannulation via artificial vessel effectively reduces the
      incidence of structure of femoral artery, thrombosis, and lower extremity
      ischemia. Operation through femoral cannulation via artificial vessel is very
      effective in treatment of aortal dissection. Only a few cases of cerebral events
      caused by retrograde perfusion through femoral cannulation occurred in this
      group, however, with high mortality.

PMID- 11953184
TI  - [Computer aided intracranial aneurysm embolization with GDC].
AB  - OBJECTIVE: To establish an expert system that automatically generates optimal GDC
      selection program for the embolization of intracranial aneurysm. METHODS: Twenty
      highly cost-effective cases of intracranial aneurysm embolized with GDC dense
      packing were collected. Each of them contains information including aneurysm's
      volume measured by three-dimension digital subtraction angiography (3D DSA),
      aneurysm's location, maximum transverse diameter, maximum length diameter, and
      GDC selection program. An expert system made up of a case base, a mathematical
      model simulating experts' experience (established with the help of data mining
      techniques combining multi-layer perceptron network with polyhedrons in high
      dimensional space), and data envelopment analysis (DEA), was implemented.
      RESULTS: When the user inputted four required parameters (volume, location,
      maximum transverse diameter, and maximum length diameter) into the expert system
      and clicked the "program design" button, candidate GDC selection program(s) would
      be presented in the result box. CONCLUSION: Case base, data mining techniques,
      and DEA can be used to establish the expert system that automatically generates
      optimal GDC selection program for the embolization of intracranial aneurysm. Its
      clinical value needs to be further evaluated.

PMID- 11953186
TI  - [Effect of psychological factors on visceral sensation of patients with irritable
      bowel syndrome].
AB  - OBJECTIVE: To investigate the features of selective attention in patients with
      irritable bowel syndrome (IBS) and the effect of psychological hint on visceral
      sensation in IBS patients. METHODS: A set of 36 modified investigation cards
      originally developed for depression patients and including 12 cards describing
      gastrointestinal (GI) symptoms, 12 cards describing respiratory symptoms, and 12
      cards with neutral terms, was used to investigate selective attention. 36
      patients with diagnosis of IBS based on Rome II criteria, 23 patients with
      asthma, and 26 healthy volunteers, all without hemorrhoid, were asked to select
      one card from the set and put it in an envelop. A rectal balloon was inserted
      into the rectum of the examinees, then the balloon was inflated by pumping air so
      as to distend the rectum and the thresholds of initial filling sensation,
      evacuation sensation, urgent evacuation sensation, and utmost tolerance sensation
      were recorded. The examinees were asked to talk about something so as to divert
      their attention, and then examination of thresholds of rectal sensation and the
      time needed for diverting attention were recorded. After a rest for 5
      approximately 10 minutes, the examinees were asked to fill the contents of
      selective attention they still remembered in a recording card. Then pictures of
      anatomy and pathology of colon were shown and conversation about gastrointestinal
      diseases was made to the examinees (as malignant stimuli) the changes of
      thresholds were recorded again. RESULTS: More terms about GI diseases were
      selectively recalled by the IBS patients than by asthma patients and healthy
      controls (all P < 0.001). During rectal distention, IBS patients had lower
      thresholds of initial sensation (21 +/- 5 mm Hg), evacuation sensation (36 +/- 9
      mm Hg), urgent evacuation sensation (51.3 +/- 14.2 mm Hg), and utmost tolerance
      sensation (67 +/- 17 mm Hg) in comparison with the other two groups (both P <
      0.001). After diverting the examinees' attention by talking and reading, the
      thresholds of the above mentioned different kinds of sensation in different
      groups increased significantly as compared with the basic values (all P < 0.05),
      in particular, the threshold of initial sensation in IBS patients increased
      markedly (P < 0.01). Focusing the examinees' attention on GI stimuli by reading
      pictures of malignant gastrointestinal diseases significantly decreased the
      sensation thresholds in IBS patients (P < 0.05). However, no remarkable change in
      the thresholds was recorded in the nonpatients. CONCLUSION: Selective attention
      of GI symptoms is the cognitive-behavioral characteristic of patients with IBS.
      Diverting the examinees' attention may decrease their response to stimuli.
      Psychological hint exerts significant influence on the rectal pain sensitivity of
      IBS patients. Psychotherapy may be helpful in treatment of IBS.

PMID- 11953185
TI  - [Microsurgical anatomy of the perforating arteries on the third ventricular
      floor].
AB  - OBJECTIVE: To study the microvascular anatomy of the perforating arteries on the
      third ventricular floor. METHODS: The microanatomy of perforating arteries on the
      third ventricular floor in 25 cadaveric heads of adults was observed with 4 to 40
      power surgical microscope. RESULTS: The perforating arteries on the third
      ventricular floor arose from the internal carotid, posterior communicating,
      posterior cerebral and basilar arteries, and could be divided into three
      patterns: no ramification, proximal ramification, and distal ramification,
      according to their vascular origin and course. The perforating arteries of
      proximal ramification pattern had larger diameter and broader distribution These
      perforating arteries terminated at relative distant area, including a) anterior
      part: the optic chiasm and stalk and infundibulum; b) middle part: mamillary body
      and tuber cinereum; c) posterior part: posterior perforated substance and
      posterior fossa; and d) lateral part: paramedian perforated substance and
      anterior portion of optic tract. In middle part overlap and anastosis of
      perforating artery with posterior communicating artery from both sides were
      relatively few. CONCLUSION: The perforating arteries on the third ventricular
      floor can be divided into three patterns. The proximal ramification pattern
      possesses larger diameter of the vessel and broader blood supply area on the
      third ventricular floor. Identification and preservation of these perforating
      arteries are important when surgery is being planed.

PMID- 11953187
TI  - [Abnormal metabolism of glucose as clue for early diagnosing pancreatic cancer].
AB  - OBJECTIVE: To investigate the incidence, features, and course of abnormal
      metabolism of glucose in patients with pancreatic cancer and the possibility of
      using the abnormal metabolism of glucose as early precursory manifestation of
      pancreatic cancer. METHODS: Fasting plasma-sugar (FPG), plasma insulin and C
      peptide were examined in 98 patients with pancreatic cancer diagnosed by B mode
      ultrasonography, CT, endoscopy, and pathological examination. The family history
      of DM was collected. The body mass index (BMI) was calculated. The relation
      between abnormal metabolism of glucose and diagnosis of pancreatic cancer was
      analyzed. One hundred and fifteen patients with advanced gastric cancer (AGC), 87
      patients with colon cancer, and 146 patients with type 2 diabetes mellitus (DM)
      were used as controls. RESULTS: Abnormality of FPG, insulin and C peptide was
      found in 17 out of the 98 patients with pancreatic cancer, with an incidence rate
      of 17.4%, significantly higher than that in patients with AGC (1/115, 1.7%, P <
      0.05), and patients with colon cancer (5/87, 5.8%, P < 0.025). Thirty eight
      patients with type 2 DM (39.0%) had their BMI > 24, while no pancreatic cancer
      patients with abnormality of metabolism of glucose had his BMI > 24 (0/17, 0%, P
      < 0.05). The duration between the discovery of abnormal metabolism of glucose and
      the diagnosis of cancer in the 17 patients was 10.8 +/- 7.4 months, and was < 2
      years in 15 of them (88.2%), significantly longer than the duration between the
      appearance of symptoms and the diagnosis in the 146 type 2 DM patients (21/146,
      14.4%, P < 0.05). The proportion of positive DM family history was 1/17 in
      patients with pancreatic cancer, significantly lower than in patients with type 2
      DM (97/146, 66.4%, P < 0.05). However, the values of FPG, insulin, and C peptide
      between the groups with and without pancreatic cancer were not significantly
      different. CONCLUSION: Clinical manifestations of abnormal metabolism of glucose
      appear prior to the discovery of space occupying lesions in pancreas in about 17%
      patients with pancreatic cancer. Newly appearing abnormalities in metabolism of
      glucose in patients without DM family history and without symptom of obesity
      should be regarded as important clues for early diagnosing pancreatic cancer.

PMID- 11953188
TI  - [Single-stage combined anterior-posterior stabilization and fusion for superior
      and distant cervical spine fractures].
AB  - OBJECTIVE: To evaluate the applicability and safety of single-stage combined
      anterior-posterior stabilization and fusion for superior and distant cervical
      spine fracture. METHODS: Ten patients with superior and distant cervical spine
      fracture and/or dislocation aged 30 approximately 68, 8 males and 2 females,
      underwent single-stage combined anterior-posterior stabilization and fusion. For
      most cases, especially those whose inferior cervical fracture was without
      complete bilateral lock of small joints, anterior procedures were performed,
      including subtotal corpectomy or diskectomy and allograft iliac crest and plates
      placement, prior to the posterior procedures. For those cases with unstable
      superior cervical fracture and inferior cervical fracture with bilateral lock of
      small joints, posterior procedures, including the application of Apofix or Atlas
      instruments to reposition the atlanto-axial joint, were performed prior to
      anterior procedures. A hard cervical collar was used postoperatively in all
      patients. All patients were followed up for 29 months on average. RESULTS:
      Satisfying fusion and reduction was obtained in all 10 patients (100%). There
      were no cases of nerve root injury, strut graft extrusion, or plate or screw
      looseness or fracture. CONCLUSION: The combined single-stage anterior-posterior
      stabilization, reconstruction, and instrumentation procedure represents a viable
      option in the treatment of a group of patients with superior and distant cervical
      spine fracture. The technique provides immediate rigid stabilization of the
      cervical spine, eliminates the need for Halo immobilization or skull distraction
      and helps begin functional exercise dirigation earlier.

PMID- 11953189
TI  - [Identification of the origin of single nucleated red blood cells and free DNA in
      peripheral blood of pregnant women].
AB  - OBJECTIVE: To investigate the feasibility of using single fetal nucleated red
      blood cells (FNRBCs) and free DNA for noninvasive prenatal diagnosis. METHODS:
      116 samples of maternal blood were analyzed. Single FNRBCs were isolated from the
      peripheral blood samples of 51 pregnant women with the gestational period of 14
      to 26 weeks by micromanipulation techniques after density gradient
      centrifugation. Nested polymerase chain reaction method was used to amplify the
      SRY gene. Plasma DNA in blood samples of 65 pregnant women with the gestational
      period of 5 approximately 40 weeks were extracted and primer extension
      preamplification (PEP) and nested polymerase chain reaction were employed to
      amplify the SRY gene. Chorionic tissue/amniotic cells were extracted to compare
      the concordance between the examination result of the meternal blood and that of
      chorionic tissue/amniotic cells. Venous blood of healthy men and unpregnant women
      were used as controls. RESULTS: (1) The detection rate of single nucleated red
      blood cells was 90.20% (46/51). (2) The concordance rate of SRY gene
      amplification results of single cells with real fetal sex was 82.61% (38/46), the
      sensitivity rate was 80.00% (24/30), and the specificity rate was 87.50% (14/16).
      (3) The concordance rate of SRY gene amplification results of free DNA with real
      fetal sex was 90.77% (59/65), the sensitivity rate was 89.13% (41/46), and the
      specificity rate was 94.74% (18/19). CONCLUSION: (1) The single nucleated red
      blood cells and free DNA in maternal blood are of fetal origin and can be one of
      the valuable material sources for prenatal diagnosis. (2) The detection purity of
      FNRBC by using micromanipulation techniques is nearly 100% and it provides a new
      way for noninvasive prenatal diagnosis.

PMID- 11953190
TI  - [Protective effect of tetramethylpyrazine on red blood cells during
      autotransfusion].
AB  - OBJECTIVE: To evaluate the protective effect of tetramethylpyrazine (TMPZ) on red
      blood cells (RBCs) during autotransfusion. METHODS: Sixty patients undergoing
      autotransfusion were randomly divided into 2 groups, 30 in each. In group I TMPZ
      with the dose of 4 mg/kg was injected intravenously to the patients before their
      blood was collected and put into the washing fluid consisting of heparinized
      normal saline with the end concentration of 5%. In group II TMPZ of the same dose
      was given to the patients too but no TMPZ was put into the washing fluid. The
      retrieval rate of RBC was calculated according to formula. The morphology of RBCs
      was observed by microscopy. Fluorescence spectrometry was used to examine the
      free calcium concentration in RBCs ([Ca(2+)]i) in the venous blood before
      anesthesia and the retrieved blood of the same patients. RESULTS: There was no
      difference in the [Ca(2+)]i in RBCs before ther were washed between the two
      groups (P > 0.05). After the RBCs were washed, the [Ca(2+)]i increased in both
      groups (34 nmol/L +/- 10 nmol/L vs 48 nmol/L +/- 17 nmol/L in group I, P < 0.05;
      and 38 nmol/L +/- 9 nmol/L vs 76 nmol/L +/- 23 nmol/L in group II, P < 0.01), and
      the difference between the two groups were statistically significant (P < 0.05
      approximately 0.01). The retrieval rate of RBCs was 69% +/- 8% in group I, higher
      than that in group II (50% +/- 16%, P < 0.05). Abnormal RBCs and fragments of
      RBCs were less in group I than in group II. CONCLUSION: RBCs undergo destruction
      to a certain degree during retrieval and washing. TMPZ protects RBCs from
      destruction through its calcium block, negative charge, and antioxidation
      effects. Pretreatment of the patients with TMPZ and addition of TMPZ into the
      washing fluid improve the quality of retrieved blood, increase the retrieval rate
      of blood, and decrease the destruction of RBCs.

PMID- 11953191
TI  - [Disseminated Penicillium marneffei infection associated with AIDS, report of a
      case].
AB  - OBJECTIVE: To explore the clinical and laboratory features of disseminated
      Penicillium marneffei infection in patients with AIDS. METHODS: The HIV antibody
      in serum was assayed by both enzyme immunoassay (EIA) and Western immunoblot
      (WIB) methods. Morphology of the pathogenic fungus in smear and biopsy specimens
      of bone marrow was observed. The fungus was isolated from the patient's skin
      lesion and inoculated into the abdominal cavities of 2 rats and 2 mice. Twenty
      days later the rats and mice were killed and their viscera were taken out. Blood
      from the organs were cultured in Sabourand glucose agar at 25 degrees C and 37
      degrees C. The colonies were observed. The morphology of the fungus was observed
      by microscopy and scanning electron microscopy. RESULTS: The most common clinical
      manifestations of Penicilium marneffei infection were fever, weight loss, anemia,
      papular skin lesion, hepatosplenomegaly, and lymphadenectasis. Yeast-like cells
      were found in the culture at 37 degrees C or in tissues. The fungi outside the
      host cells were elongated, often curved, sausage-like and with clear central
      septi. When cultured at 25 degrees C, the fungus was mycelia-like and produced a
      characteristic red pigment, diffusing into the medium. CONCLUSION: Disseminated
      Penicilliosis marneffei is one of the most important opportunistic infections in
      patients with AIDS in Southeast Asia and the southern part of China. Since there
      is no specific clinical manifestation for Penicillium marneffei infection, it is
      often misdiagnosed. Definite diagnosis requires culture of the pathogenic fungus
      from clinical specimens. The fungus is thermally dimorphic, produces red pigment,
      and is sausage-form with clear central septum outside the host cell. Amphotericin
      B and itraconazole are effective in treating Penicilliosis marneffei.

PMID- 11953192
TI  - [Growth properties of hematopoietic stem/progenitor cells in the second or third
      trimester and term fetal cord blood].
AB  - OBJECTIVE: To investigate the growth properties of hematopoietic progenitor/stem
      cells in umbilical cord blood (CB) of second trimester, third trimester, and term
      fetuses. METHODS: Blood was collected by umbilical cord puncture in 27 just
      delivered fetuses, including 16 term babies and 11 preterm fetuses. Mononuclear
      cells were isolated. CD34(+) cells were enriched and isolated using the MACS. The
      frequencies of CD34(+), CD34(+) CD38(-) and CD34(+) HLA-DR(+) cells were
      determined by fluorescence-activated cell sorting. The proliferative and self
      renewal capacity and expansion response to varying concentrations of defined
      growth factors were determined by short or long-term liquid culture and
      methylcellulose self-solid culture. RESULTS: The frequency of CD34(+) and CD34(+)
      CD38(-) cells in CB and the frequency of CD34(+) CD38(-), CD34(+) HLA-DR(+) cells
      among CB CD34(+) cells were significantly higher in preterm CB than in term CB
      (3.14% and 0.76% vs 0.78% and 0.18%; and 9.8% and 20.4% vs 3.9% And 14.6%; P <
      0.001). The number of colony forming units (CFUs) in preterm CB was higher and
      was correlated with the content of CD34(+) cells (r = 0.83). The number of long
      term culture initiating cells (LTC-IC) in preterm CB was about 3 times as much as
      in term CB (5.7 +/- 1.2/10(5) cells vs 1.7 +/- 0.8/10(5) cells, P < 0.05),
      Progenitors from preterm CB could be expanded in short-term liquid cultures
      supplemented with hematopoietic growth factors as efficiently as progenitors from
      term CB, the peaks of expansion in terms of CFU, CD34(+) cells and CD34(+) CD38(
      ) cells were all at day 7, in particular under the condition of combining the
      early-acting and late-acting growth factors together (SCF + FL + TPO + IL-3 + IL
      6). CONCLUSION: The frequency of hematoietic stem/progenitor cell in umbilical
      cord blood of preterm fetus (especially of mid-term fetus) is significantly
      higher than in CB of term babies. The hematoietic stem/progenitor cells in
      umbilical cord blood of preterm fetus have greater colony forming capacity, are
      sensitive to growth factors, effectively expand and proliferate in vitro, and are
      preferable target cells for gene therapy.

PMID- 11953193
TI  - [Polymorphism of microsatellite markers D6S296, etc. in patients with
      schizophrenia].
AB  - OBJECTIVE: To investigate the loci associated with susceptibility to
      schizophrenia in the human chromosome 6. METHODS: Genomic DNA was isolated from
      the blood samples of 178 schizophrenia patients in Shanghai, including 82 chronic
      schizophrenics with a course of more than 10 years, and 88 healthy persons as
      controls. Amplified fragment length polymorphism (AFLP) technique was used to
      investigate the polymorphism of the four microsatellite markers: D6S470, D6S274,
      D6S296, and D9S175. RESULTS: The distribution of the allele frequencies in these
      four microsatellite markers conformed to Hardy-Weinberg equilibrum. The gene
      frequency of the allele 264 bp of D6S296 was 0.1688 in chronic schizophrenics,
      and was 0.039 0 in healthy persons (chi(2) = 17.68, P < 0.001). The gene
      frequencies of other alleles did not differ between the schizophrenics and
      controls. There was a very strong association between chronic schozophrenia and
      the allele 264 bp of D6S296 (RR = 8.30, chi(2) = 17.68, upsilon = 1, P < 0.001).
      CONCLUSION: Gene(s) associated with susceptibility to schizophrania may exist in
      the microsatellite marker region D6S296 in the chromosome 6.

PMID- 11953194
TI  - [Anti-apoptosis gene survivin promotes cell growth and transformation].
AB  - OBJECTIVE: To investigate the role and molecular mechanism of surviving, an anti
      apoptosis gene, in cell growth and transformation. METHODS: Coding sequence of
      surviving was amplified from Daudi cell mRNA by RT-PCR and then cloned into
      prokaryotic and eukaryotic vectors. The vectors with surviving were transfected
      into BL21 cells of Escherichia coli and human embryonic kidney 293 cells. The
      cells were cultured. Protein was extracted from the cells and examined by gel
      electrophoresis. Suspension of 293 cells was cultured and the number of cells was
      counted every other day, thus a growth curve was drawn. Another suspension of 293
      cells was cultured in soft agar to observe the number of colonies. Cells
      transfected with plasmids void of surviving were used as controls. RESULTS: The
      anti-apoptosis gene surviving was well expressed in BL21 cells and 293 cells. The
      growth curve showed that the proliferation rate of 293 cells was slightly faster
      than that of control cells, however, without significant difference. Soft agar
      assay showed that the colonies formed by surviving-transfected 293 cells were of
      greater size and with greater number. Western blotting showed overexpression of
      cyclin D1 and c-myc, two important cancer proteins, in cells transfected with
      surviving. CONCLUSION: The anti-apoptosis gene surviving promotes cell
      transformation. These effects may depend on the functions of cyclin D1 and c-myc.

PMID- 11953196
TI  - [Teratosis and damage of viscera induced by microcystin in SD rat fetuses].
AB  - OBJECTIVE: To study the teratogenicity and traumatic effect of microcystin LR
      (MCLR) on pregnant SD rats and their fetuses. METHODS: Sixty pregnant SD rats
      were divided into four groups, 16 in each group: three experimental groups in
      which MCLR was injected into the abdominal cavity at the doses of 4 microgram/kg,
      16 microgram/kg, and 62 microgram/kg respectively for 10 days, and control group
      injected with normal saline. Twenty days after, the pregnant rats were killed.
      The development, teratosis, and histology of viscera of the fetuses were
      examined. RESULTS: Deformities were found in the fetuses of the 62 microgram/kg
      group and 16 microgram/kg group with the teratogenic rate of 11.70 per thousand
      (2/172) and 6.76 per thousand (1/155). Petechial hemorrhage and severe hydropic
      degeneration in liver and maldevelopment of glomeruli and renal medulla were
      found in 62 microgram/kg group. Mild granular degeneration was found in the liver
      of fetuses in 4 microgram/kg group. CONCLUSION: MCLR passes through the placental
      barrier and causes damage in kidney and liver, which may be the basis of high
      incidence of liver cancer microgram in the fetus phase.

PMID- 11953195
TI  - [Nanoparticle as a new gene transferring vector in specific expression gene].
AB  - OBJECTIVE: To evaluate the possibility and efficiency of nanoparticle as a new
      vector in specific gene transference. METHODS: Nanoparticle-DNA complex was
      prepared with PLGA bearing antisense monocyte chemotactic protein-1 (A-MCP-1), a
      specific expression gene, and the package efficiency, release progress in vitro,
      and size of the complex were determined. The nanoparticl-DNA was trasnsfected
      into the cultured smooth muscle cells. PCR was used to evaluate the transfection
      of A-MCP-1. Cationic lipid (lipofectamine) was used to transfect A-MCP-1 as
      control. Forty-eight hours later, DNA in the SMCs was extracted and examined by
      PCR. Twenty New Zealand White rabbits underwent jugular vein-to-artery bypass
      grafting procedure, of which 6 received grafts transfected with nanopaticle-A-MCP
      1 (200 microgram), 6 received grafts with cationic liposome (DOTAP)-A-MCP-1 (200
      microgram), 4 received grafts with LNCX plasmid, and 4 received grafts without
      transfection as control. Fourteen days after surgery grafts were harvested. The
      expression of A-MCP-1 and its effect on MCP-1 in vein grafts were detected by dot
      blotting. The morphology of the grafts was investigated. RESULTS: The package
      efficiency, release progress in vitro, and size of the nanoparticle-DNA complex
      thus prepared were 0.9%, 2 week, and 150 nm approximately 300 nm respectively.
      Genomic DNA PCR showed that A-MCP-1 gene could be successfully transfected into
      smooth muscle cells by nanoparticle. Two weeks later, antisense MCP-1 was
      expressed in the vascular walls of the groups with transfection methods by
      nanaoparticle or by cationic lipid to an almost same degree. The degree of
      vascular hyperplasia in gene transfection groups was lower than that in control
      group. There was no significant difference in inhibition of intimal hyperplasia
      between the two groups of transfection by different vectors. CONCLUSION:
      Nanoparticle acts as a vector to transfect specific gene in vitro and in vivo.

PMID- 11953197
TI  - [RhoA gene expression in colorectal carcinoma].
AB  - OBJECTIVE: To investigate the expression of RhoA mRNA in colorectal neoplasms.
      METHODS: Total RNA was extracted from 42 surgically resected specimens of
      colorectal caricinoma and normal mucosa close to the lesions. Afier the optimal
      reverse transcription polymerase chain reaction (RT-PCR) condition was found, the
      mRNA expression levels of the RhoA gene in the lesions and the normal mucosa were
      examined semi-quantitatively and the relation between these expression levels and
      clinical pathological markers was compared. RESULTS: The expression of RhoA gene
      mRNA in lesion of colorectal carcinoma was significantly higher than that in
      contiguous normal mucosa (1.8 +/- 0.6 vs 0.9 +/- 0.4, P < 0.01). The ratio of
      RhoA expression in neoplasm to that in contiguous mucosa was 2.02 +/- 0.82. Based
      on this ratio the 42 patients were divided into two groups: overexpression group
      (19 cases) and high-expression group (23 cases). In the overexpression group the
      lesions of 14 cases were in Dukes C and Dukes D stages, and lymph node metastasis
      was found in 13 cases. In the high-expression group, only 9 out of the 23 cases
      were in advanced stage and 8 cases showed lymph-node metastasis. Chi-squared test
      analysis demonstrated a significant difference in both aspects between these two
      groups (P < 0.05). The difference in number of metastatic lymph nodes between the
      two groups was statistically significant (P < 0.01). Mutation was not found in
      the RhoA gene sequence examined. CONCLUSION: RhoA gene may play an important role
      in colorectal carcinogenesis and correlate with invasion and metastasis of
      colorectal carcinoma.

PMID- 11953198
TI  - [Effects of higeramine on hemodynamics and its tolerability and safety, an
      experimental study].
AB  - OBJECTIVE: To investigate the effects of higeramine (HG) on hemodynamics and its
      tolerability and safety so as to see if it can be used in cardiac loading test,
      and to compare the hemodynamic effects of HG and dobutamine (DB). METHODS: Six
      dogs were infused intrevenously with HG in escalating doses from l
      microgram/kg/min through 2 microgram/kg/min and to 4 microgram/kg/min, each dose
      being given for 5 minutes. Then the dogs were infused intravenously with DB at
      the escalating doses from 5 microgram/kg/min through 10 microgram/kg/min to 20
      microgram/kg/min, each dose being given for 5 minutes. Heart rate (HR), blood
      pressure (BP), cardiac output (CO), myocardial oxygen consumption (MOC), and
      coronary blood flow (CBF) were measured at the beginning of test and by the end
      of each dose-infusion. Electrocardiography was conducted in the meantime. Left
      ventricular ejection fraction (LVEF) was measured with radionuclide equilibrium
      ventriculography. Another 8 dogs were given HG at the escalating doses from 1
      microgram/kg/min up to 500 microgram/kg/min, each dose being infused for 3
      minutes, to observe the tolerability and safety of HG, HR, BP, and ECG were
      monitored during the test. RESULTS: Intravenous administration of HG results in
      significant inotropic and chronotropic effects on the heart. HR, MOC, CO and CBF
      all increased in a dose-dependent manner in both HG and DB tests. HG did not
      cause significant change in systolic blood pressure (SBP), but a slight decrease
      in diastolic blood pressure (DBP) was found. HR increased steeply to the peak,
      and then remained at a plateau level. No significant ECG abnormality was seen
      except a few occasional premature ventricular beats. No dog died during the
      study. CONCLUSION: HG can be used in pharmacological stress test with remarkable
      tolerability and safety even at the dosage of 500 microgram/kg/min without
      serious adverse effect. It can be used as an alternative agent to DB under
      appropriate circumstances.

PMID- 11953200
TI  - [Regional intra-arterial infusion chemotherapy for pancreatic cancer: an
      experimental study].
AB  - OBJECTIVE: To verify the feasibility of regional intra-arterial infusion
      chemotherapy with gemcitabine for the treatment of locally advanced pancreatic
      cancer. METHODS: 10 Beagle dogs were divided into two groups: the experimental
      group and the control group. In the experimental group, gemcitabine (45 mg/kg)
      were infused via a transfemorally placed catheter into the celiac axis and
      superior mesenteric artery. IAC was given over 30 min with the help of DSA. In
      the control group, chemotherapy was performed via peripheral veins with the same
      dosage as the experimental group. Blood samples, heart, lung, liver, kidney,
      pancreas and parapancreatic tissues were obtained for drug concentration
      determination and pathological examination. RESULTS: The serum concentration of
      experimental group were significantly higher than those of the control group 2
      hr, 4 hr and 8 hr after treatment (P < 0.05). Area under curve after dosage-based
      calibration in experimental group was much higher than that in control group (P <
      0.05). The mean retention time of the drug in the animal body was significantly
      longer in experimental group than in control group. Pancreatic gemcitabine titer
      in experimental group was significantly higher than that in control group 4 hr
      and 8 hr after drug administration. There were a large number of red blood cells
      in the renal glomerulus and tubules, congestion and hemorrahge in the pulmonary
      capillaries and myocardium in the control group according to pathological
      examinations. However, infiltration of neutrophilic white blood cells, hemorrahge
      and fibrinous exudation were present in parapancreatic tissues which were absent
      in the group. CONCLUSION: Regional intra-arterial infusion chemotherapy with
      gemcitabine could increase serum and pancreatic drug concentration, prolongs
      retention time of the drug in the animal body, and is feasible in the treatment
      of pancreatic cancer.

PMID- 11953199
TI  - [Binding pancreaticojejunostomy: clinical report of 150 cases].
AB  - OBJECTIVE: To study the safety and feasibility of a new operative procedure
      called binding pancreaticojejunostomy (BPJ) used to prevent anastomotic leakage
      following pancreatoduodenectomy (PD). METHODS: From 1996 to 2001, a newly
      developed operative procedure, binding pancreaticojejunostomy, was performed upon
      150 cases undergoing PD. The remnant of pancreas was sutured with and invaginated
      into the jejunum, with the suture needle only penetrating the mucosa and not the
      seromuscular layer. The mucosa of jejunum near the pancreatic remnant was
      destroyed by electric coagulation or phenol. The pancreas and jejunum were bound
      together so that they were pressed close to each other. The clinical data were
      reviewed and analysed. RESULTS: The operation of BPJ was performed smoothly on
      all 150 patients. No pancreatic leakage occurred. CONCLUSION: The BPJ procedure
      is effective in avoiding anastomotic leakage following PD.

PMID- 11953201
TI  - [Non-functional islet-cell tumor: analysis of 237 cases].
AB  - OBJECTIVE: To summarize the clinical aspects of nonfunctional islet-cell tumor
      (NIT) reported in Chinese periodicals. METHODS: Articles in Chinese on NIT were
      screened from the Chinese Bio-Medical Database (1981.1 - 1999.10). Data of
      epidemiology, clinical manifestations, diagnosis, defferential diagnosis, and
      treatment of NIT were analyzed. RESULTS: 60 articles and 237 cases of NIT were
      selected. The female to male ratio was 2.9:1. Abdominal mass was the most common
      clinical symptom. It was difficult for the pre-operative diagnosis of NIT and
      differentiation from pancreatic tumor or retroperitoneal mass. The malignant rate
      of NIT was 35%. The five-year survival rate of malignant NIT was 53.1%.
      CONCLUSION: NIT is rare. It occurs more often in female than in male. The
      preoperative diagnostic rate is rather low. The prognosis of malignant NIT is
      favorable. Active treatment is strongly recommended.

PMID- 11953202
TI  - [Relationship between HLA-DQA1, -DQB1 genes polymorphism and susceptilibity to
      bronchial asthma among Northern Hans].
AB  - OBJECTIVE: To investigate the relationship between human leukocyte antigen (HLA)-
      DQA1, -DQB1 genes polymorphism and susceptibility to bronchial asthma among the
      Hans in the northern China. METHOD: Sequence-specific primer polymerase chain
      reaction was used to gene frequencies of HLA-DQA1 and HLA-DQB1 genes among 125
      unrelated asthmatics, 12 of which being probands of asthmatic pedigrees, and 96
      healthy controls, all of Han nationality and living in Beijing or nearby areas
      for a long time. Radioimmunosorbent test was used to examine the serum IgE and
      TigE. The ventilatory function was test among the asthmatics. RESULTS: The
      frequencies of HLA-DQA1 0104 and HLA-DQB1 0201 were 0.204 and 0.284,
      significantly higher than those in the healthy controls (0.089 and 0.096
      respectively, both P < 0.01). Conversely, the frequencies of HLA-DQA10301 and HLA
      DQB101301 in the asthmatics were 0.148 and 0.20, significantly lower than those
      in the controls (0.25 and 0.282 respectively, P < 0.01 and < 0.05). The
      correlation coefficients between HLA-DQA1 * 0104 and atopy, HLA-DQB1 * 0201 and
      atopy, and HLA-DQA1 * 0301 and atopy were 0.813 (P < 0.01), 0.289 (P < 0.01), and
      -0.168 (P < 0.05) respectively. Multi-variate logistic regression asthma.
      CONCLUSIONS: The alleles HLA-DQA1 * 0104 and HLA-DQB1 * 0201 are correlated with
      the susceptibility to asthma among Northern of Han nationality. HLA-DQA1 * 0104
      is an independent risk factor of onset of asthma. The alleles HLA-DQA1 * 0301 and
      HLA-DQB10301 are correlated with resistance against asthma. HLA-DQ genes are
      involved in the regulation of human specific immune responses.

PMID- 11953203
TI  - [Activation of nuclear factor-kappaB and effects of anti-inflammatory treatment
      thereon in intestinal mucosa of patients with ulcerative colitis].
AB  - OBJECTIVE: To investigate the activation and expression of nuclear factor-kappaB
      (NF-kappaB) and effects of anti-inflammatory treatment on NF-kappaB in the
      intestinal mucosa of patients with ulcerative colitis (UC). METHODS: Ten pieces
      of colon mucosal biopsy specimens were obtained from 31 cases with UC, 17 of
      which received sulphasalazine (SASP) or SASP plus glucocorticoid and 14 of which
      received no medication. Samples of normal mucosa around the lesion taken from 11
      patients with colon cancer were used as controls. NF-kappaB DNA binding activity
      was evaluated by electrophoretic mobility shift assay. NF-kappaB p65 expression
      was determined by Western blot analysis and immunohistochemical staining with a
      NF-kappaB p65 antibody. The type of cells containing activated NF-kappaBp65 was
      identified by double immunofluorescence confocal laser scanning microscopy.
      RESULTS: The expression of NF-kappaB p65 and NF-kappaB DNA binding activity were
      significantly higher in patients with UC than in the control (P < 0.05), and were
      correlated with the degree of inflammation. The NF-kappaB expression was
      significantly stronger in the nuclei than in the cytoplasm in patients with UC
      without pharmacotherapy. The NF-kappaB expression in nuclei was significantly
      stronger in the group without pharmacotherapy than in the group with
      pharmacotherapy (P < 0.05). Only a few NF-kappaB p65 positive cells were seen in
      the controls. NF-kappaBp65 expression was found in all major subsets of
      mononuclear cells, including macrophages, B lymphocytes, T lymphocytes, and
      cryptal epithelial cells. CONCLUSION: The increased activation of NF-kappaB and
      increased expression of NF-kappaB may be involved in the pathogenesis of UC.
      Glucocorticoids and SASP strongly inhibited NF-kappaB activation and expression.
      The inhibition of NF-kappaB activation may be a central part of the anti
      inflammatory action of glucocorticoids and SASP, which might represent an
      important pharmacological mechanism in treatment of patients with UC. NF-kappaB
      will be an important target for cytokine-based therapy of UC.

PMID- 11953204
TI  - [Cognitive functions of children with attention deficit/hyperactivity disorder].
AB  - OBJECTIVE: To investigate the features of cognitive function in children with
      attention deficit/hyperactivity disorder (ADHD). METHODS: Wechsler Intelligence
      Scale for Children-RC, Wechsler Memory Scale (WMS), Number Cancellation Test,
      Ravin's Standard Progressive Matrices, and Stroop test were conducted among 60 7
      approximately 12-year-old children diagnosed with ADHD and 60 children matched by
      age, sex, and maternal education level. RESULTS: The verbal intelligence
      quotient, performance IQ, full scale IQ, verbal comprehension IQ, perceptual
      organization IQ, and freedom from distractibility IQ of the ADHD CHILDREN were
      104 +/- 13, 98 +/- 14, 102 +/- 13, 100 +/- 15, and 102 +/- 15, all less than
      those of the controls (112 +/- 11, 108 +/- 13, 112 +/- 12, 111 +/- 12, 107 +/-
      13, and 116 +/- 13, all P < 0.01). The scores of long-term memory, short-term
      memory, immediate memory, memory quotient, and reverse digit span in the children
      with ADHD were 40 +/- 7, 58 +/- 12, 7 +/- 3, 95 +/- 15, and 4.2 +/- 1.7
      respectively, all less than those in the controls (49 +/- 5, 63 +/- 10, 8.4 +/-
      3.0, 109 +/- 12.5, and 5.0 +/- 1.4 respectively, all P < 0.05). Number
      cancellation test showed significantly lower total score and higher error rate in
      ADHD children than in the controls (51.5 and 76.4 VS 77.3 and 38.0, both P =
      0.000). In Stroop test, the ADHD children spent more time for all the four parts,
      had to make more effort to eliminate the interference of word meaning, and made
      more errors in the C and D parts. The average standard score of Raven's Standard
      Progressive Matrices was 4.0 +/- 1.5, significantly higher than that in the
      controls (2.7 +/- 1.2, P = 0.000). CONCLUSION: The levels of intelligence,
      memory, and attention in ADHD children are lower that those in normal children.
      ADHD children have deficiency in executive functions, such as selective
      inhibition, working memory and plan implementation.

PMID- 11953205
TI  - [Influencing factors of local immunocyte infiltration in hepatocellular carcinoma
      tissues pre- and post-percutaneous microwave coagulation therapy].
AB  - OBJECTIVE: To investigate the influencing factors of the local immunity in
      tissues of hepatocellular carcinoma (HCC) before and after percutaneous microwave
      coagulation therapy (PMCT). METHODS: Seventy-eight patients with HCC diagnosed by
      needle biopsy of liver underwent PMCT. Before the treatment and three and 17 days
      after the treatment specimens of carcinoma tissues were obtained by ultrasound
      guided liver biopsy. The extents of infiltration of CD3(+) cell, natural killer
      cells (CD56(+)), and macrophages (CD68(+)), and the expression rate of
      proliferating cell nuclear antigen (PCNA) were evaluated by immunohistochemistry.
      The relation between the extents of immunocyte infiltration and the clinical
      parameters was analyzed with multiple regression. RESULTS: Before PMCT
      infiltration of the three kinds of immunocytes was found in the carcinoma tissues
      to different degrees with a great variation among individuals. A remarkable
      increase in the extent of infiltration of the three kinds of immunocytes was
      found three days after the treatment and continued or remained till the 17th post
      PMCT day (P < 0.01). The post-PMCT extent of immunocyte infiltration was
      positively correlated with the pre-PMCT extent (CD3(+): r = 0.256, P = 0.005;
      CD56(+): r = 0.257, P = 0.002; CD68(+): r = 0.275, P = 0.001). A negative
      correlation was found between the extent of immunocyte infiltration and serum
      alpha-fetal protein (AFP) and between the extent of immunocyte infiltration and
      tumor size (for serum AFP, CD3(+): r = -0.075, P = 0.049; CD56(+): r = -0.062, P
      = 0.041; CD68(+): r = -0.007, P = 0.035; for tumor size, CD3(+): r = -0.074, P =
      0.051; CD56(+): r = -0.100, P = 0.012; CD68(+): r = -0.109, P = 0.038). No
      correlation was found between the extent of immunocyte infiltration and age of
      patient, Child-Pugh class of tumor, grade of tumor differentiation, and number of
      tumor. The extent of immunocyte infiltration was lesser in the carcinoma tissues
      with higher expression rate of PCNA. The extent of immunocyte infiltration was
      greater in the carcinoma tissues where PCNA expression was negative and carcinoma
      cells had necrotized but with their structure recognizable. No immunocyte
      infiltration was found in the necrotic and structureless tumor tissues.
      CONCLUSION: The local immunocyte infiltration in patients with HCC was influenced
      by serum AFP and the grade of tumor cell necrosis pre- and post-PMCT. Destruction
      of tumor tissue in situs by PMCT is the premise of increase of immunocyte
      infiltration. Before PMCT improving the immune status of the patients helps
      enhance the local immune response.

PMID- 11953206
TI  - [Anxiety and depression in patients with viral hepatitis].
AB  - OBJECTIVE: To investigate the anxiety and depression in patients with viral
      hepatitis. METHODS: A retrospective survey was conducted among 118 patients with
      viral hepatitis hospitalized in Renmin Hospital, Wuhan University, from 1999 to
      2000 using self-rating anxiety scale (SAS) and self-rating depression scale
      (SDS). RESULTS: The average SAS score in patients with viral hepatitis was 44 +/-
      10, significantly higher than the norm (34 +/- 6, P < 0.01). The average SDS
      score in patients with viral hepatitis was 44 +/- 10, significantly higher than
      the norm (42 +/- 11, P < 0.025). The average SDS in patients with chronic viral
      hepatitis was 45 +/- 10, significantly higher than that in patients with acute
      viral hepatitis (42 +/- 11, P < 0.05). The average SAS in female patients with
      viral hepatitis was 47 +/- 11, significantly higher than that in male patients
      (43 +/- 7, P < 0.05). CONCLUSION: Patients with hepatitis have symptoms of
      anxiety and depression to a certain degree.

PMID- 11953207
TI  - [A novel stop codon mutation in S gene: the molecular basis of a patient with
      cryptogenic cirrhosis].
AB  - OBJECTIVE: To explore the pathogen and molecular basis of cryptogenic cirrhosis
      in a patient. METHODS: Serum was collected from a patient, male, aged 56, with
      cryptogenic cirrhosis. HBV serologic markers were qualitatively tested, and
      HBsAg, HBeAg, and anti-HBc were quantitatively determined again. HBV DNA in serum
      was qualitatively tested using PCR, and quantified using fluorescence
      quantitative PCR. S gene was amplified, cloned, and sequenced. RESULTS: HbsAg and
      anti-Hbe were negative, and anti-HBs, HBeAg, anti-HBc, and HBV DNA were all
      positive. HBsAg (S/N) was 0.77 (cutoff of S/N: >/= 2.00), HbeAg (S/N) was 56.43
      (cutoff of S/N: >/= 2.10), anti-HBc (S/C(O)) was 0.03 (cutoff of S/C(O): </=
      1.00); HBV DNA was 1.54 x 10(9) copies/ml. An uncommon point mutation at
      nucleotide 336 (C to A) in S gene was found, resulting in the change of the 61st
      codon into a novel stop codon and failure of synthesis of HbsAg. CONCLUSION: HBV
      proves the pathogen of this case. This special mutation well explains the
      patient's unusual serologic pattern. Moreover, this finding possesses important
      clinical and theoretical significance.

PMID- 11953209
TI  - [The clinical features and treatment of cerebral cavernous angiomas in children].
AB  - OBJECTIVE: To discuss the clinical features, diagnosis and treatment of cerebral
      cavernous angiomas in children. METHODS: The clinical data of 30 cases of
      cavernous angioma hospitalized in the past 11 years, 25 boys and 5 girl, with an
      average age of 9.4 years, of which 27 underwent operation, were analyzed
      retrospectively. RESULTS: Epilepsy and focal neurological deficits caused by
      repeated hemorrhage of lesion were the most common symptoms. MRI appearances were
      mainly high or complex abnormal signal. Ring-shaped low signal could be seen
      around the lesions by T1 and T2, especially by T2. The results of operation were
      satisfactory. CONCLUSION: MRI examination is the best method for diagnosis and
      follow-up of cerebral cavernomas. Operation is the first choice for paediatric
      cavernous angioma.

PMID- 11953208
TI  - [EMG activities of the head, neck and upper trunk muscles with mandibular
      movements in healthy adults and mandibular asymmetry patients].
AB  - OBJECTIVE: To study the activities of head, neck and upper trunk muscles during
      mandibular movements in healthy adults and mandibular asymmetry patients.
      METHODS: Electromyographic integrogram was used to record and analyze the
      electromyographic activities of the anterior temporal (Ta), posterior temporal
      (Tp), sternocleidomastoid (SCM), and trapezius (TRAP) muscles in rest position
      and during mandibular movement among 10 normal adults and 10 mandibular asymmetry
      patients. RESULTS: All the four muscles showed constant electromyographic
      activities when the mandible was in the rest position. The activities of Ta, Tp,
      and SCM muscles increased with protrusion of mandible, mouth opening, tapping,
      maximum clenching, and chewing. The activities of Ta and Tp muscles of the
      patients were 1.7 times greater than that of the normal adults during mandibular
      movement without occlusion, and were weaker by 50% during mandibular movement
      with occlusion. The difference between electromyographic activities during
      mandibular movement and in rest position was less among patients than among
      normal adults. The TRAP muscle of the patients showed constant electromyographic
      activities with the activity volume nearly 1.8 times that of the normal adults.
      The difference between the muscle and its namesake at the opposite side was
      greater among the patients (21%) than among the normal adults (8%). CONCLUSION:
      All the four muscles participate in the maintenance of rest position of mandible
      and the realization of mandibular movements. The coordination of muscular
      activities among mandibular asymmetry patients is poorer than that among normal
      adults.

PMID- 11953210
TI  - [Relation between insulin-like growth factor-1 and insulin resistance in patients
      with acute stroke].
AB  - OBJECTIVE: To study the changes of plasma insulin-like growth factor -1 (IGF-1)
      and IGF binding protein 3 (IGFBP3) in patients with acute cerebral infarct (ACI)
      and acute cerebral hemorrhage (ACH) and the correlation of IGF-1 and IGFBP3 with
      plasma fasting insulin (FINS) related to insulin resistance (IR) and with insulin
      sensitive index (ISI). METHODS: The plasma IGF-1, IGFBP3 and FINS of 34 patients
      with ACI and 40 patients with ACH (within 2 days after onset) were measured by
      radioimmunoassay. Meanwhile, the fasting blood glucose (GS) of these patients was
      measured. 30 patients with ACH during convalescence (3 approximately 6 months
      after stroke) and 30 age-matched healthy individuals served as control groups.
      RESULTS: (1) The plasma IGF-1 and IGFBP3 and ISI were 17.3 +/- 7.0 mmol/L, 72.9
      +/- 11.4 mmol/L and -4.2 +/- 0.3 respectively in the ACI group, 14.4 +/- 5.8
      mmol/L, 57.8 +/- 17.2 mmol/L and -4.7 +/- 0.6 in the ACH group; 28.8 +/- 13.6
      mmol/L, 87.4 +/- 18.3 mmol/L and -3.9 +/- 0.4 in the convalescence group; and
      31.5 +/- 18.9 mmol/L, 93.1 +/- 28.0 mmol/L and -3.6 +/- 0.3 in the healthy
      control group. The values in the former two groups were significantly lower than
      those in the two control groups (F = 18.3, 20.2 and 17.2 respectively, P < 0.01).
      The plasma glucose was 6.1 +/- 1.0 mmol/L in ACI group, 6.4 +/- 2.1 mmol/L in ACH
      group, and 4.8 +/- 0.5 mmol/L in healthy control group (F = 8.5, P < 0.01). The
      plasma FINS was 15.7 +/- 3.1 mIU/L in ACI group, 19.7 +/- 9.6 mIU/L in ACH group,
      and 10.6 +/- 3.2 mIU/L in healthy control group (F = 10.6, P < 0.01). (2) In
      patients with ACI and ACH, there was a significant positive correlation between
      plasma IGF-1 and IGFBP3 (P < 0.01), between plasma IGF-1 and ISI (P < 0.01), and
      between IGFBP3 and ISI (P < 0.05); and there was a significant negative
      correlation between plasma IGF-1 and FINS and between IGFBP3 and FINS (P < 0.01).
      CONCLUSION: The plasma IGF-1 and IGFBP3 participates in the pathophysiologic
      course of ACI and ACH in the early stage. Insulin resistance exists in ACI and
      ACH. Plasma IGF-1 may play an important role in IR in ACI and ACH.

PMID- 11953211
TI  - [Expression of fusion proteins in beta(2)GP I gene-transfected HEp-2 cells and
      its clinical application].
AB  - OBJECTIVE: To establish an indirect immunofluorescent test so as to improve the
      sensitivity and specificity of examination of antibodies to beta(2)-glycoprotein.
      METHODS: Full-length beta(2)GP cDNA was obtained from human hepatocellular cancer
      cell line HepG2 by RT-PCR and cloned into the mammalian expression vector pEGFP
      C1. The recombinant plasmid pEGFP-beta(2)GP was transfected into HEp-2 cells. RT
      PCR, immunoblotting (IBT), confocal fluorescence microscopy, and indirect
      immunofluorescent test (IIF) were used to confirm the expression, localization,
      and antigenicity of fusion protein of green fluorescent protein (GFP). Serum
      specimens from 19 patients suspected as with secondary antiphospholipid syndrome
      (APS), 1 patient diagnosed as with primary APS, and 10 normal persons were
      detected with IIF-IgG-beta(2)GP1, ELISA-IgG-ACL, and ELISA-IgG-beta(2)GP I
      simultaneously. RESULTS: (1) The HEp-beta(2)GP I cells thus obtained retained
      their ability of expression of beta(2)GP-I-GFP for more than ten generations.
      This beta(2)GP-I-GFP showed the antigenicity of beta(2)GP-I with a characteristic
      feature. (2) Seven of the 20 serum specimens from APS patients showed
      characteristic immunofluorescent pattern. No serum specimen from normal persons
      showed immunofluorescent staining. The comparison of results of the three methods
      showed that the concordance between IIF-IgG-beta(2)GP I and ELISA-IgG-beta(2)GP I
      was the most perfect (Kappa = 0.886). (3) HEp-beta(2)GP I retained the
      immunofluorescent property of HEp-2 cell. CONCLUSION: As a new kind of substrate
      of IIF, beta(2)GP I transfectant can be used to detect anti-beta(2)GP-I
      antibodies. Transfeted HEp-2 cells keep the immunofluorescent property of HEp-2
      cells in IFANA test and can be used as substrate for routine IFANA detection.

PMID- 11953212
TI  - [Impact of ligation of vertebral artery on function of central nervous system, an
      experimental study].
AB  - OBJECTIVE: To study the impact of ligation of bilateral vertebral arteries on the
      function of central nervous system. METHODS: Twenty dogs underwent ligation of
      bilateral vertebral arteries at the level of C4 approximately C5 and then were
      divided into 4 groups, 5 in each: E1 group (killed in one day after the
      operation), E7 (killed on the 7(th) day postoperatively), E28 (killed on the
      28(th) day postoperatively), and control group. Scoring of the function of
      central nervous system was conducted after awakening from anaesthesia and before
      being killed according ro modified Tarlov method. Cortical somatosense evoked
      potential (CSEP), and motor evoked potential (MEP) were examined by
      electromyograph. CT, MRI, and magnetic resonance angiography (MRA) of the
      cervical vertebrae were conducted before the dogs were killed. Histological
      examination of the spinal cord and brain was made and microangiography was
      performed. RESULTS: The myodynamia, gait, and reflex returned to normal 2
      approximately 3 days after the operation with the Tarlov score of 6 for all dogs.
      Imaging examination and histological examination showed no abnormality, including
      ischemic injury in posterior inferior lobe of cerebellum. CONCLUSION: Internal
      carotid artery compensates for the blood obstruction of the vertebral artery in a
      short time. Cerebral ischemia caused by compression of the vertebral artery is
      not the main pathomechanism of cervical spondylotic arteriopathy.
      Microcirculation of human cervical cord can be mimicked in dog model segmentally.

PMID- 11953213
TI  - [Insulin mitigates the effect of free fatty acid to cause endothelial dysfunction
      in rat aortic rings].
AB  - OBJECTIVE: To investigate whether free fatty acid (FFA) directly and
      independently causes endothelial dysfunction and whether enhancing insulin action
      mitigates FFA-induced endothelial dysfunction. METHODS: Twenty-nine S-D rats were
      divided into 4 groups and infused by jugular catheterization with different
      solutions: 20% intralipid + heparin (0.72 IU/min) for 4 hours (FFA group, n = 9),
      short-acting insulin by hyperinsulinemic euglycemic clamp for 4 hours (Ins group,
      n = 5), intralipid + heparin and insulin by hyperinsulinemic euglycemic clamp for
      4 hours (Ins + FFA group, n = 10), and normal saline (18 microliter/min) for 4
      hours(C group, n = 5). After the infusion, the rats were killed and their aortic
      rings were resected and put into organ bath and connected to a force transducer
      and amplifier. PGF2a was added into the organ bath to constrict the rings until
      the constriction tension reached a balance. Then acethylcholine (Ach) and sodium
      nitroprusside (SNP) of increasing concentrations were added to relax the rings to
      record the endothelial dependent vasodilatation (EDV) and endothelium independent
      vasodilatation (EIV). RESULTS: The EDV value was 85.0% +/- 3.2% in C group and
      54.8% +/- 2.5% in FFA group (C vs FFA, P = 0.002); 80.6% +/- 1.8% in Ins group (C
      vs Ins, P = ns); 72.8% +/- 2.1% in Ins + FFA group (FFA + Ins vs C P = 0.02, FFA
      + Ins vs FFA, P = 0.005). The EIV response in the three experimental groups was
      not different from that in the control group. CONCLUSION: FFA damages the
      endothelisal dependant vasodilatation of aorta, thus causing endothelial
      dysfunction by direct interaction with the endothelium. FFA may be
      proatherogenic. Hyperinsulinemia has salutary effects on endothelial function in
      the context of elevated FFA.

PMID- 11953214
TI  - Community-acquired bacteremia among hospitalized children in rural central
      Africa.
AB  - OBJECTIVE: To describe the epidemiology of community-acquired bacteremia in
      children admitted to a rural hospital in central Africa and to identify useful
      diagnostic signs or symptoms. METHODS: On admission, a blood culture was obtained
      from all children admitted to Children's Hospital of Lwiro between 1989 and 1990.
      Clinical and biologic signs of infection and nutritional status were recorded.
      RESULTS: Among the 779 children included in the study, 15.9% were bacteremic on
      admission. The rate of bacteremia was the highest among children with jaundice
      (20/56; 35.7%) and fever (119/487; 24.4%). In contrast, children with severe
      malnutrition had a lower rate of bacteremia (13.2%) than weight growth retarded
      or well-nourished children (19.5%) (P = 0.046). Fever was the most useful
      diagnostic criteria (sensitivity and negative predictive value of 96.0% and
      97.8%, respectively) even in severely malnourished children (sensitivity and
      negative predictive value of 96.4% and 99.1%, respectively). Enterobacteriacea,
      mostly Salmonella spp, caused 73% of the bacteremia. There was a high rate of
      resistance to ampicillin and chloramphenicol among the responsible organisms.
      Only 31 (47.7%) of 65 bacteremic children responded to the combination of
      ampicillin and gentamicin. The presence of bacteremia on admission did not
      significantly increase the risk of morality during hospitalization (19.4%
      compared with 13.5%; P = 0.088). Age less than 12 months and jaundice were
      independent risk factors for deaths in bacteremic children. CONCLUSIONS:
      Community-acquired bacteremia caused by multiresistant Enterobacteriacea is an
      important problem of hospitalized well-nourished and malnourished children in
      central Africa. Fever on admission is a sensitive diagnostic sign, even in
      malnourished children.

PMID- 11953215
TI  - Ordinary and opportunistic enteropathogens associated with diarrhea in Senegalese
      adults in relation to human immunodeficiency virus serostatus.
AB  - OBJECTIVES: A survey was conducted in Dakar, Senegal, to identify major types and
      prevalences of bacteria, parasites, fungi, and Rotaviruses associated with
      diarrhea in relation to human immunodeficiency virus (HIV) serostatus with the
      goal to provide guidance to physicians for case management. METHODS: Etiologic
      agents were identified in a case control study: cases were HIV-infected patients
      with diarrhea (HIV+ D+) and HIV seronegative patients with diarrhea (HIV D+);
      controls were HIV-infected patients without diarrhea (HIV+ D ) and seronegative
      controls without diarrhea (HID D ). Ordinary enteric pathogens were identified by
      conventional methods. Different Escherichia coli pathotypes were characterized by
      polymerase chain reaction (PCR), identification of HEp-2 cell adherence pattern,
      Sereny test, GM1-ELISA, and the suckling mouse assay. Opportunistic parasites,
      such as Cryptosporidium and Microsporidium, were identified by the Kinyoun method
      and trichromic stain of Weber, respectively. Rotaviruses were identified with a
      commercial latex agglutination kit. Antimicrobial susceptibility testing was
      carried out by the disk diffusion method. RESULTS: Among the 594 patients
      examined, 158 were HIV+ D+, 121 were HIV2 D+, 160 were HIV+ D , and 155 were HIV
      D . The main etiologies of diarrhea were different according to HIV serostatus of
      patients. In immunocompetent adults the main causes of diarrhea were Shigella sp
      (12.4%), Entamoeba histolytica(10.7%), Salmonella enterica (6.6%), and Giardia
      (4.9%). In the immunocompromised host the more frequent pathogens were
      enteroaggregative E. coli (19.6%), Microsporidium (9.4%), Cryptosporidium sp
      (8.2%), Rotavirus (8.2%), Shigella sp (7.6%), Candida albicans (7.6%), E.
      histolytica (5.1%), S. enterica (4.4%), and Isospora belli (4.4%). Also,
      Blastocystis hominis has to be considered as an opportunistic parasite, because
      it was identified only in HIV-infected patients, with higher prevalence in adults
      with diarrhea (2.5% in HIV+ D+ patients; 0.6% in HIV+ D patients). High level of
      asymptomatic carriage of Ascaris lumbricoides and Trichuris trichiura and some
      cases of multiple infections were observed. Fungi, Cryptosporidium sp and
      Microsporidium sp, were often identified in patients with low CD4 counts (range,
      79 250 cells/mL). Independently from HIV-serostatus, CD4 count was lower in
      diarrheic persons, suggesting that diarrhea is a debilitating illness and that
      effective management of diarrhea can prevent immunosuppression. Isolated
      enteropathogenic strains displayed high resistance to most antibiotics used in
      Senegal for treating diarrhea (ampicillin, tetracycline, cotrimoxazole); they
      were susceptible to amikacin, gentamicin, and norfloxacin. CONCLUSION: These
      epidemiologic data suggest that guidelines for the management of diarrhea during
      HIV infection in Dakar should be updated.

PMID- 11953216
TI  - Obstacles to penicillin use in treating pneumococcal infection.
AB  - OBJECTIVES: To determine the pattern of penicillin use in the treatment of
      pneumococcal pneumonia, and factors contributing to the use of alternative
      antibiotics. METHODS: This study included all adult inpatients of St. Vincent's
      Hospital and Medical Center who had documented pneumococcal pneumonia between
      December 1998 and October 1999. St. Vincent's is a 600 bed tertiary teaching
      hospital in New York City. Patients who had Streptococcus pneumoniae isolated
      from a respiratory tract specimen were identified through microbiology laboratory
      records. A retrospective chart review of these patients was conducted, and those
      identified with clinical pneumonia were included in this study. Antibiotic use,
      patient demographics, resistance data, and clinician awareness of the antibiotic
      susceptibility results were noted. RESULTS: Sixty adult patients hospitalized
      with documented pneumococcal pneumonia were identified. Thirteen (21.6%) of the
      60 patients received penicillin or ampicillin. Susceptibility results were not
      noted in the medical record in 21 (35.0%) of the 60 patients, and none received
      penicillin. High rates of reported penicillin allergy in 8 (13.3%) of the 60
      patients, and reluctance to use penicillin when isolates demonstrated
      intermediate susceptibility in 8 (13.3%) of the 60 patients were observed.
      CONCLUSIONS: Several remediable obstacles to penicillin use were identified in
      this study. An increased awareness of susceptibility results by physicians and
      education of practitioners could have increased the use of penicillin as therapy
      to two-thirds of these patients.

PMID- 11953217
TI  - Loss of maternally derived human herpesvirus-6 immunity and natural infection in
      Argentinian infants.
AB  - BACKGROUND: Human herpesvirus-6 (HHV-6) infection is widespread throughout the
      world. No data are available in Argentina about the loss of maternally derived
      HHV-6 immunity and natural infection in infants. METHODS: A population of 100
      pregnant women and 407 children between 1 and 15 months of age were assayed by
      indirect immunofluorescence to detect and quantify specific IgG anti-human
      herpesvirus-6 (anti-HHV-6) antibodies in Cordoba City, Argentina. RESULTS: There
      was no significant difference in the positive rate between infants aged 1 to 9
      months (range, 43.6 35.5%) and pregnant women (37%). Seropositive ratio dropped
      in the 10-month group (23.33% seropositive) and rose sharply in the 11-month
      group (38.89%), 12-month (60.61%), and 13- to 15-month group (63.46%). The
      geometric mean titer (GMT) for infants in the 12 to 15 months age group (23.4
      41.64) was significantly higher than the GMT for infants 10 months of age (11.04)
      (P < 0.05 with the Tukey-HSD test). CONCLUSIONS: This study shows a significant
      association between loss of passive HHV-6 antibody and age among infants. The
      results support evidence that HHV-6 enters the susceptible population at 11
      months, leading to a high prevalence of antibodies in children between 13 and 15
      months of age.

PMID- 11953218
TI  - Cluster analysis on multiple drugs susceptibility supplements genotyping of
      methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: To evaluate the typing power of cluster analysis of antimicrobial
      susceptibility. METHODS: Results of pulsed-field gel electrophoresis in 71
      strains of methicillin-resistant Staphylococcus aureus were compared with cluster
      analysis of the diameter of growth inhibition in 11 drugs. Subjects were a
      consecutive series of patients (n = 71) from the wards and outpatient units of a
      community teaching hospital. RESULTS: The cluster analysis took 2 to 3 seconds
      once the data were entered into a computer. The sensitivity, specificity, and
      accuracy of the cluster analysis were 76.3%, 58.3%, and 73.2%, respectively,
      using genotyping as the reference. CONCLUSIONS: The cluster analysis offered real
      time epidemiologic data at minimal cost and labor, warranting its cost-effective
      role.

PMID- 11953219
TI  - Prevalence of hepatitis virus infections in Kosovar refugees.
AB  - OBJECTIVES: To assess the prevalence of viral hepatitis infections in a sample of
      Kosovar refugees having arrived in southern Italy as a result of the 1999 war in
      the Balkans. METHODS: The 526 subjects who enrolled on voluntary basis from all
      age groups were tested for the prevalence of serologic markers for hepatitis
      virus types A, B, C, D, and E (HAV, HBV, HCV, HDV, HEV). RESULTS: Among the 526
      refugees, the prevalence of total anti-HAV antibodies was 81%. A relevant finding
      was the presence of total anti-HAV antibodies in 61% of the children up to 10
      years of age. The prevalence of anti-HEV antibodies was 2.5% among the subjects.
      Fifteen subjects (2.9%) were positive for hepatitis B surface antigen (HBsAg),
      whereas 17.5% tested positive for anti-hepatitis B core antigen (anti-HBc). In
      children up to 10 years of age, the prevalence of HBsAg and anti-HBc was found to
      be 0.4% and 6%, respectively. In subjects aged 11 to 20 years, 4.2% tested
      positive for HBsAg and 20.2% for anti-HBc. In the age group 21 to 30 years, 7.1%
      of the subjects were found to be HBsAg carriers, whereas 25.9% were found to be
      positive for anti-HBc. Among the refugees over 30 years of age, the prevalence of
      HBsAg was 4.2%, whereas anti-HBc was 43.7%. None of the refugees tested positive
      for anti-HDV. The prevalence of anti-HCV antibodies was 0.7%. CONCLUSIONS: The
      results of this seroepidemiologic study indicate a high circulation of HAV in the
      Kosovar population, whereas the prevalence of HEV antibodies was low and
      comparable to that of other European countries. The HBV infection seems to be at
      an intermediate level of endemicity and an immunization policy against HBV
      infection, through vaccination of all newborns and children before adolescence,
      may be advisable. Results of this study indicate that the level of endemicity of
      HCV infection in the Kosovar population is low.

PMID- 11953220
TI  - Are the environmental niches of Vibrio cholerae O139 different from those of
      Vibrio cholerae O1 El Tor?
AB  - BACKGROUND: Vibrio cholerae are known to be normal inhabitants of surface water.
      However, the environmental niches of the different strains of cholera are not
      well known, and therefore, populations at risk for cholera outbreaks cannot be
      clearly identified. METHODS: This study identifies environmental risk factors for
      cholera caused by V. cholerae O1 El Tor and O139 and environmental niches of the
      two strains present in Matlab, a cholera endemic area of Bangladesh. The study
      year was 1993, the year that the O139 strain first appeared in the study area.
      Patients who had either strain of cholera identified in a laboratory were
      included in the study. A geographic information system was used to map the
      household locations of the patients, to describe the human sanitary environment
      and population density, and to address potential anthropogenic and environmental
      risk factors of the disease. Spatial point pattern and exploratory spatial data
      analysis techniques were used to define the environmental niches of the two
      cholera strains. RESULTS: The study suggests the niches of O1 El Tor and O139
      strains of V. cholerae appear to be similar, based on common environmental risk
      factors. CONCLUSIONS: The results of this study support a theory that O1 El Tor
      could possibly be replaced by the newer O139 strain in the future.

PMID- 11953221
TI  - Anthrax meningitis: case report.

PMID- 11953222
TI  - Pulmonary nocardiosis after bone marrow transplantation successfully treated with
      doxycycline.

PMID- 11953223
TI  - Acute terminal ileitis mimicking Crohn's disease caused by Salmonella veneziana.

PMID- 11953224
TI  - Salmonella westerstede vertebral osteomyelitis and sepsis in an immunocompetent
      patient.

PMID- 11953225
TI  - Antiretroviral therapy in pregnant women of Florence.

PMID- 11953226
TI  - Pulmonary infection due to Brucella melitensis.

PMID- 11953227
TI  - Perceptions of the family mealtime environment and adolescent mealtime behavior:
      do adults and adolescents agree?
AB  - The family mealtime environment has great potential to affect the eating
      behaviors of youth in the family. It is difficult to determine the important
      elements of a healthy mealtime environment because a valid assessment of the
      family environment is so difficult to obtain.The objective of this study is to
      examine the level of agreement between adult and adolescent perceptions of the
      family mealtime environment and adolescent mealtime behavior.A telephone survey
      was used to query adult and adolescent family members about how they perceive the
      family mealtime environment and the adolescent's mealtime behavior. A convenience
      sample of 282 adult/adolescent pairs from four schools in the Minneapolis/St.
      Paul area completed the telephone surveys. Frequencies of responses and the
      associations between the adult and adolescent responses are presented. Pearson
      correlations and regression were used to examine the level of association between
      adult and adolescent responses. Mixed-model regression was used for the
      continuous variables, and mixed-model logistic regression was used for the
      dichotomous variables. This study showed very little concordance between
      adolescent and adult responses. Only one question regarding arguments about
      eating during mealtime showed concordance. Adults and adolescents living in the
      same household seem to have different perceptions of the family mealtime
      environment and adolescent eating patterns. Researchers need to be aware of and
      concerned with the validity of the use of self-report for descriptions of family
      mealtime. They also need to be aware of the difference in adult and adolescent
      perceptions and consider these differences when designing messages for the
      family.

PMID- 11953228
TI  - Factors associated with the intention to use vitamin D supplements: quantitative
      study among a sample of elderly people in a medium-sized town in the Netherlands.
AB  - The objective of this study was to assess which factors are related to the
      intention of elderly people to use vitamin D supplements.A questionnaire that was
      based on several theories, feedback of experts, and personal interviews with
      members of the target group was distributed among a random sample of 497 elderly
      people in a medium-sized town in the Netherlands (response 46%). Variables
      measured included perceived susceptibility, severity and control with respect to
      developing a vitamin D deficiency or getting a bone fracture, and beliefs,
      perceived social norms, modeling, self-efficacy, and intention with respect to
      the use of vitamin D supplements. Univariate analyses of variance, chi-square
      tests, stepwise multiple regression, and stepwise logistic regression analysis
      were performed. Respondents reporting a high intention had more positive
      attitudes and normative beliefs, higher self-efficacy expectations with respect
      to using vitamin D supplements, and more often used other supplements than
      respondents with a low intention. Subjects who already used vitamin D supplements
      were more often female and already familiar with the advice and had more positive
      attitudes and normative beliefs than nonusers. It was concluded that many elderly
      people have high intentions to start using vitamin D supplements as soon as they
      hear about the advice. A health promotion campaign to promote the use of vitamin
      D supplements should aim at making elderly people familiar with the Health
      Council of the Netherlands' advice. Furthermore, the campaign should place
      emphasis on changing attitudes, perceived social norms, and self-efficacy
      expectations toward vitamin D supplement use.

PMID- 11953229
TI  - Mothers' sources of information about feeding their children ages 2 months to 54
      months.
AB  - The purpose of this study was to determine sources and types of information about
      child feeding practices that were received by 62 mothers with children aged 2 to
      54 months. Each mother participated in 10 or 11 in-home interviews. Data analyses
      included chi-square testing for differences in information sources over time and
      content analyses to develop information themes. As sources, citations for
      professionals and magazines decreased, with no significant changes for relatives
      over time. After 24 months, newspapers, television, and friends were reported
      more frequently than earlier. Mothers reported multiple and concurrent
      information sources over time. Thus, nutrition educators have concurrent and
      multiple opportunities to disseminate nutrition information.

PMID- 11953230
TI  - Practices and perceptions of food safety among seniors who prepare meals at home.
AB  - Given senior citizens' vulnerability for food-borne illness, a need exists to
      determine the necessity and focus for education. Focus groups at senior centers
      reveal that the seniors (N=74) who prepare more than five meals a week at home
      use both inappropriate and appropriate practices to cook, cool, and thaw foods.
      Seniors rely of the distant past for knowledge and identify barriers to altering
      practices but state that information from educators about the health effects of
      inappropriate practices will convince them to change. For future food safety
      education, seniors recommend programs, videotapes, television, newspapers, radio,
      church bulletins, and written educational pieces.

PMID- 11953231
TI  - Interpretations of the "balanced meal" household food security indicator.
AB  - The study objective was to quantify interpretations of the term "balanced meals"
      used in food security status assessments. Telephone interviews included 77
      charitable food recipients in Hawaii. After participants first responded to the
      question of whether they could afford to eat balanced meals, they next defined
      what a "balanced meal" meant. Qualitative responses were categorized into common
      themes. Forty-one (53%) indicated that a balanced meal consisted of at least
      three food groups.Thirty-one (40%) indicated something other than three food
      groups; five (6%) had no idea what a "balanced meal" meant. The findings question
      the validity and reliability of responses to "balanced meal" food security
      indicators in Hawaii.

PMID- 11953232
TI  - Evaluation of a preschool nutrition education program based on the theory of
      multiple intelligences.
AB  - This report describes the evaluation of a preschool nutrition education program
      based on the theory of multiple intelligences. Forty-six nutrition educators
      provided a series of 12 lessons to 6102 preschool-age children. The program was
      evaluated using a pretest/post-test design to assess differences in fruit and
      vegetable identification, healthy snack choices, willingness to taste foods, and
      eating behaviors. Subjects showed significant improvement in food identification
      and recognition, healthy snack identification, willingness to taste foods, and
      frequency of fruit, vegetable, meat, and dairy consumption. The evaluation
      indicates that the program was an effective approach for educating preschool
      children about nutrition.

PMID- 11953233
TI  - Response shift bias: a problem in evaluating nutrition training using self-report
      measures.
AB  - The Cooperative Extension Service has been a key partner in the design,
      implementation, and evaluation of school nutrition training. To evaluate the
      effectiveness of their training and the effects of response shift bias on
      outcomes using a self-report measure, 162 foodservice staff from eight rural
      schools participated in this food-handling behavior study. Nutrition staff were
      assigned to one of two treatment groups or to the control group. Two different
      evaluation designs (pretest/ post-test and then/post) were used. The then/post
      design asks participants to first report their behavior or understanding as a
      result of the training (post) and then to retrospectively report this behavior
      before the training. The then/post evaluation design provided more significant
      change data than did the traditional pretest/post-test design, indicating that a
      response shift occurred. Such differences in evaluation findings suggest that the
      educational benefit of such training may be underestimated when using the
      traditional pre/post evaluation design.

PMID- 11953234
TI  - School food service "Computer Exploration Kit".

PMID- 11953235
TI  - Two internet diet analysis programs.

PMID- 11953236
TI  - WHEEL OF NUTRITION Game: nutrition in the round.

PMID- 11953240
TI  - Healthy eating: what does it mean to adolescents?
AB  - OBJECTIVE: The objective of this study was to investigate the meanings of
      "healthy" and "unhealthy" eating and the importance of healthy eating among
      adolescents. DESIGN: Twenty-five structured focus groups were conducted.
      SUBJECTS: These focus groups consisted of 203 adolescent girls and boys enrolled
      in three senior high schools and one junior high school. VARIABLES MEASURED: The
      variables measured were adolescents' self-report of perceptions of healthy and
      unhealthy eating and their descriptions of the importance of healthy eating to
      adolescents. ANALYSIS: Data analysis was done by general content coding and
      specific content coding. RESULTS: Adolescents have a significant amount of
      knowledge regarding healthy foods and believe that healthy eating involves
      moderation, balance, and variety. Despite this knowledge, they find it difficult
      to follow healthy eating recommendations and frequently consume foods that they
      perceive as unhealthy. Barriers to healthy eating include a lack of time, limited
      availability of healthy foods in schools, and a general lack of concern regarding
      following healthy eating recommendations. IMPLICATIONS: These findings suggest
      that healthy eating messages based on the Dietary Guidelines for Americans are
      reaching adolescents, but interventions are needed that assist adolescents with
      the translation of this knowledge into healthy behaviors. Interventions should
      help make healthy eating easy for youth to apply and explain the consequences of
      unhealthy eating in terms that they value, stressing meaningful short-term
      benefits.

PMID- 11953239
TI  - Sample extensiveness in qualitative nutrition education research.
AB  - OBJECTIVE: Extensiveness represents the amount of information gathered in
      qualitative research. This study examined sample extensiveness in qualitative
      nutrition education research. DESIGN: Retrospective analysis was performed on
      articles published in the Journal of Nutrition Education (JNE) from 1969 to 1999
      (Volumes 1 to 31). SUBJECTS: Content analysis was used to code articles and the
      studies they reported as units of analysis. OUTCOME MEASURES: Articles were coded
      to determine whether they included one or more studies using qualitative research
      and, if so, the types of qualitative studies performed, the sample extensiveness
      of each study, and mention of sample extensiveness limitations in the article.
      STATISTICAL ANALYSES: The statistics used were univariate (counts, percentages,
      means, medians, modes, ranges) and bivariate (chi-square, correlations). RESULTS:
      Of the published JNE articles, 71 (8%) used qualitative methods, and most (85%)
      qualitative articles were published in the 1990s. Some (19%) of these articles
      reported using multiple qualitative methods. The 30 studies using individual
      interviews interviewed an average of 45 people (range 15-155). The 38 studies
      using group interviews averaged 15 groups (range 1-180) and 141 people (range 9
      900). Ten studies used observation/fieldwork, and eight used other types of
      qualitative research, with mixed [corrected] patterns of sample extensiveness in
      those studies. Few articles made specific statements about limitations based on
      sample extensiveness. IMPLICATIONS: Sample extensiveness in qualitative research
      in JNE varied considerably. Future qualitative research would benefit from more
      explicit attention to sample extensiveness.

PMID- 11953241
TI  - Qualitative investigation of the meanings of eating fruits and vegetables for
      adult couples.
AB  - OBJECTIVE: The purpose of this study was to develop a substantive theory
      expressing the meanings couples associated with eating fruits and vegetables.
      DESIGN: This inductive qualitative study was based on a grounded theory approach
      and employed the constant comparison method of data analysis. Data were collected
      using semistructured individual interviews and a life history approach. SUBJECTS:
      Ten adult couples, aged 20 to 60 years, with and without children, all of whom
      were born in North America, were recruited using modified snowball sampling.
      RESULTS: Two overarching themes emerged. The "should syndrome" describes a
      morality concerning fruit and vegetable consumption arising from a tension
      between the low status of these foods in participants' childhood homes and their
      contemporary idealized status. The creation of couple gastronomies expresses
      couples'efforts to construct their own food norms and practices within a context
      of changes in social norms and fruit and vegetable availability. The substantive
      theory, making choices that balance their lives, conveys the dynamic processes
      involved in participants' fruit and vegetable choices. IMPLICATIONS: Future
      research will determine the transferability of the "should syndrome" and new
      couples' receptiveness to trying new fruits and vegetables. Understanding the
      changing contexts of food choice may help nutrition professionals better support
      healthful eating.

PMID- 11953242
TI  - Understanding weight stigmatization: a focus group study.
AB  - OBJECTIVES: The purpose of this research was to investigate, in a nonclinical
      sample of adults, thoughts on and experiences with weight stigmatization. DESIGN:
      Focus groups were used to collect information. Participants were recruited
      through a newspaper advertisement and flyers posted in public places in
      Minneapolis and St. Paul. During the focus groups, participants were led in a
      discussion about their thoughts on weight stigmatization and personal experiences
      of being treated differently or poorly because of their weight. SUBJECTS: Six
      gender-specific focus groups consisted of 31 adult volunteers (17 women and 14
      men). VARIABLES MEASURED: Perceptions of weight-based stereotypes and weight
      stigmatization and personal reports of having been treated differently or poorly
      owing to weight were measured. RESULTS: Participants reported a variety of
      experiences of being treated differently or poorly because of their weight. These
      included teasing, harassment, slurs and insults, negative judgments and
      assumptions, and perceived discrimination. Participants reported that such
      experiences occurred at home, among friends and strangers, at work, and in health
      care settings. Women reported a greater number and a greater variety of negative
      experiences than men. IMPLICATIONS: The results indicated that participants
      experienced weight-based stigmatization in many aspects of their lives. Awareness
      of these experiences may assist in the development of treatments for overweight
      individuals.

PMID- 11953244
TI  - Food selection and eating patterns: themes found among people with type 2
      diabetes mellitus.
AB  - OBJECTIVE: The objective of this study was to examine the beliefs and
      perspectives among people with type 2 diabetes mellitus about dietary
      requirements, food selection and eating patterns, and attitudes about self
      management practices. DESIGN: Semistructured, in-depth interviews explored
      participants' experiences with diabetes prior to their diagnosis, participants'
      understanding of the guidelines for the nutritional management of diabetes, how
      participants applied their understanding of dietary guidelines to daily food
      selection and eating patterns, and the social and personal themes influencing
      participants' food selection and eating patterns. SUBJECTS: Interviews were
      conducted with members of a convenience sample of 45 men and women diagnosed with
      type 2 diabetes for at least 1 year. ANALYSES PERFORMED: Interviews were coded
      using a conceptual matrix derived from participants' statements. Common
      characteristics were grouped, and broad themes were identified. RESULTS: Eating
      patterns were influenced by participants' knowledge of diabetes management.
      Challenges that participants encountered when applying nutrition recommendations
      were linked to their prior eating practices. Dietary self-efficacy, social
      support, and time management were identified as mediating variables that can
      influence dietary behaviors. IMPLICATIONS: Diabetes nutrition education programs
      should increase awareness of eating history, spousal support, and time management
      practices. Future research should include the refinement and validation of a
      nutritional management model of diabetes.

PMID- 11953243
TI  - Consistency in women's orientations to food and nutrition in midlife and older
      age: a 10-year qualitative follow-up.
AB  - OBJECTIVE: The objective of this study was to discover and understand women's
      perceptions of stability and change in their orientations to food and nutrition
      during a time of physical, social, and psychological transitions. DESIGN: A 10
      year follow-up to a 1988 study was conducted. PARTICPANTS/SETTINGS: Seventeen
      women from a 1988 study in a semirural county in New York participated. They were
      well-educated, Caucasian mothers, aged 44 to 75 years in 1998. METHODS:
      Semistructured, qualitative interviews in 1988 and 1998 were analyzed using
      grounded theory analysis. The 1998 and 1988 interviews with the same women were
      compared to understand patterns in orientations to food and nutrition. The life
      course perspective was a conceptual guide. RESULTS: Most women in this sample
      described consistent orientations to food and nutrition at interviews 10 years
      apart. Even in the face of expected and unexpected changes in healthy, social
      environment, and roles, 14 of the 17 women perceived that their thoughts,
      beliefs, and strategies related to food and nutrition had been consistent across
      10 years. The few women who perceived that they had changed orientations
      attributed changes to debilitating disease and transitions in work and family
      roles. IMPLICATIONS: Perceptions of consistency in their orientations to food and
      nutrition through midlife and older age among these women may be signs of stable
      trajectories that influence their response to nutrition education and their
      approach to dietary change.

PMID- 11953245
TI  - Food matters: changing dimensions of science and practice in the nutrition
      profession.
AB  - OBJECTIVE: This qualitative research describes some of the social organization of
      the American nutrition profession set in place by an apparent competition between
      two kinds of knowledge-a science-based knowledge and another more experimental
      knowledge drawn from practice. DESIGN: The methodological approach is
      constructivist and uses the theoretical framework of sociologist Dorothy Smith.
      SUBJECTS AND SETTINGS: Multiple data sources include: interviews and
      bibliographic data from 23 purposefully selected subjects who taught or studied
      in a graduate-level Nutrition Program at Teacher College, Columbia University
      from 1937 to 1992; administrative reports of the Program; faculty writings;
      dissertations approved by the program; the author's twenty-five years of
      experience in the nutrition profession; and a series of diagrams drawn to
      interpret and describe the data. Subjects recounted their varied professional
      experience during the 55-year period as a part of a larger study. MAIN OUTCOME
      MEASURES: The research traces changes in the relationship between nutrition
      science and practice as shaped by underlying sciences (food, agriculture,
      nutrition and health), related industries (food and health care), and culturally
      bound gender ideals. DATA ANALYSIS: Data analysis was based on recommended
      strategies for an inductive, interpretive, ethnographic case study. RESULTS:
      Subjects identified three forms of the construct of food-as nutrients, as
      marketable products, and as nurturance. This research suggests that the nurturing
      properties of food, the knowledge this generates, and the practitioners
      associated with nurturance are vulnerable and risk disappearance inside the
      profession, due to a history of resistance to this aspect of our discipline.
      IMPLICATIONS: The author recommends collaborative research between nutritionists
      and historians, sociologists and others to bring forth a more critical history of
      this profession.

PMID- 11953246
TI  - Gem no. 336. Eat better to feel better: capitalizing on self-reported benefits of
      dietary changes.

PMID- 11953247
TI  - Gem no. 337. Team nutrition partners: a volunteer program to enhance the school
      environment.

PMID- 11953258
TI  - Travel agents and the prevention of health problems among travelers in Quebec.
AB  - BACKGROUND: Among the factors influencing travelers to seek preventive health
      advice before departure, the travel agent's recommendation plays an important
      role. The objective of our study was to document the practices and needs of
      travel agents in Quebec (Canada) in relation to the prevention of health problems
      among travelers. METHODS: In June 2000, a cross-sectional descriptive survey was
      carried out among travel agents from all travel agencies in Quebec. One agent per
      agency was asked to answer our questions. Data were collected using a 32-item
      telephone questionnaire. RESULTS: Altogether, 708 travel agents from the 948
      agencies contacted answered our questionnaire (participation rate: 75%). Most
      respondents (81%) believed that the travel agent has a role to play in the
      prevention of health problems among travelers, especially to recommend that
      travelers consult a travel clinic before departure. Although over 80% of the
      agents interviewed mentioned recommending a visit to a travel clinic before an
      organized tour to Thailand or a backpacking trip in Mexico, less than half said
      they make the same recommendation for a stay in a seaside resort in Mexico. The
      majority of respondents were acquainted with the services offered in travel
      health clinics, and these clinics were the source of travel health information
      most often mentioned by travel agents. However, nearly 60% of the agents
      questioned had never personally consulted a travel clinic. When asked about the
      best way to receive information about travelers' health, more than 40% of
      respondents favoured receiving information newsletters from public health
      departments regularly whereas 28% preferred the Internet. CONCLUSION: Despite the
      limits of this study, our results should help the public health network better
      target its interventions aimed to inform travel agents on prevention of health
      problems among travelers.

PMID- 11953259
TI  - Crossover vaccination with quadrivalent meningococcal vaccine (against A/C/Y/W
      135) following recent application of bivalent meningococcal vaccine (against
      A/C): assessment of safety and side effect profile.
AB  - BACKGROUND: Until May 2000, bivalent A/C meningococcal vaccine was the only
      available vaccine in Singapore for hajj travelers to Saudi Arabia. Recent
      worldwide reports of serogroup W-135 meningococcal meningitis associated with
      hajj returnees necessitated switching to quadrivalent A/C/Y/W-135 vaccine and
      crossover vaccination of travelers to Saudi Arabia. No safety data are available
      for quadrivalent vaccine following recent vaccination with bivalent vaccine. We
      assessed the safety and side effect profile of bivalent, quadrivalent, and
      quadrivalent meningococcal vaccine after recent vaccination with bivalent
      vaccine. METHODS: A postvaccination telephone questionnaire survey was performed
      for all travelers who received either bivalent (B), quadrivalent (Q), or
      quadrivalent with recent (as defined by less than 6 months before) bivalent
      meningococcal vaccine (BQ) between 22 May and 8 June 2000 in preparation for the
      umrah (minor pilgrimage). Patients were asked about local reactions (pain,
      erythema, swelling at injection site graded in mild, moderate, and severe) and
      systemic reactions (fever, headache, graded in mild and severe). RESULTS: Of 546
      persons vaccinated, 323 were interviewed. Median time interval between interview
      and vaccination was 10 days. Of those interviewed, 64 patients received bivalent
      (B), 213 quadrivalent (Q), and 46 quadrivalent after recent bivalent vaccine
      (BQ). The median interval time between previous bivalent and quadrivalent vaccine
      was 5 weeks. There was no statistically significant difference in the prevalence
      of side effects between the three groups. Mild pain at injection site was
      recorded in B as 21.8%, Q as 23%, BQ as 21.7%; low grade fever in B as 7.8%, Q as
      9.8%, and BQ as 15.2%. CONCLUSIONS: Bivalent and quadrivalent meningococcal
      vaccine are well tolerated. Crossover vaccination of quadrivalent meningococcal
      vaccine after recent vaccination with bivalent vaccine does not increase the
      prevalence of adverse reactions and is therefore safe.

PMID- 11953260
TI  - Health advice provided to hostelers from Australia: influence of a travelers'
      information evening.
AB  - BACKGROUND: Little is known about the health advice provided to hostelers and the
      role and influence of hosteling organizations' travelers' information evenings in
      giving travel health advice. This study was designed to investigate these in
      relation to the Australian context. METHODS: In 1997, hostelers attending
      travelers' information evenings in two regional centers and one metropolitan
      location in Queensland were asked to complete self-administered questionnaires.
      RESULTS: Of 158 questionnaires, 110 (69.6%) were returned. Missing data have been
      excluded from the analysis. About two-thirds of the hostelers attending the
      travelers' information evening reported being age 35 years or younger (43/65,
      66.2%). Almost two-thirds of attendees were female (42/65, 64.6%). The hostelers
      responding to this study were fairly evenly divided between regional centers
      (54/110, 49.1%) and the metropolitan center (56/110, 50.9%). Hostelers indicated
      that they were traveling to Europe and the United Kingdom (53/62, 85.5%), Canada
      (17/62, 27.4%), Asia (15/62, 24.2%), United States (10/52, 19.2%), and other
      destinations (7/51, 13.7%), mostly Africa. Hostelers were significantly more
      likely to have obtained travel health advice (x = 5.02, df = 1, p <.05) if they
      were traveling within 6 weeks. Hostelers indicated that they obtained advice from
      general practitioners (41/67, 61.2%), travel agents (29/67, 43.3%), books (22/67,
      32.8%), travel clinics (10/67, 14.9%), and other sources (6/67, 9.0%). Most
      hostelers indicated that they learnt something new about healthy travel from the
      travelers' information evening (76/100, 76.0%). Of those hostelers who had not
      sought travel health advice or who had not planned to seek travel health advice
      prior to the travelers' information evening, almost all indicated that they now
      would seek travel health advice (32/33, 97.0%). CONCLUSIONS: This cross-sectional
      study found that most hostelers attending an international hosteling
      organization's travelers' health information session in Australia were in the
      younger age groups and were predominantly female. Most of these hostelers had
      sought travel health advice from general practitioners, travel agents, and books.
      The information provided by the healthy travel session of the travelers'
      information evenings appeared to be of some benefit to hostelers, particularly as
      it appeared to have prompted most hostelers who had not yet sought travel health
      advice to do so.

PMID- 11953261
TI  - Epidemic meningococcal disease and travel.

PMID- 11953262
TI  - What is travel medicine? Content, current position, tools, and tasks.

PMID- 11953263
TI  - Outbreak of histoplasmosis in a school party that visited a cave in Belize: role
      of antigen testing in diagnosis.

PMID- 11953264
TI  - Mal de debarquement syndrome: a case report.

PMID- 11953266
TI  - [Bronchial asthma in rural communities].

PMID- 11953265
TI  - Melioidotic osteomyelitis of the femur occurring in a traveler.

PMID- 11953267
TI  - [Mechanical ventilation in a respiratory ward. Evolution from 1994 to 2000].
AB  - OBJECTIVE: To investigate the absolute and relative frequency of mechanical
      ventilation in the management of patients on a respiratory medicine ward between
      1994 and 2000. To describe reasons for admission, mean hospital stay and
      outcomes. SETTING: A tertiary-care university hospital. METHODS: Observational,
      descriptive study of a case series. RESULTS: During the study period, 257
      admissions involved mechanical ventilation of 132 patients. During that time,
      there was a progressive increase in the total number of ventilated patients as
      well as in the relative frequency, such that ventilated patients eventually
      accounted for 6.1% of all admissions for respiratory care in 2000. Nearly 80% of
      admissions were related to the service's home mechanical ventilation program,
      either to initiate and adapt ventilation for new patients or to treat
      exacerbations or diagnose and treat other medical or surgical problems in already
      ventilated patients. Patients transferred from the intensive care unit (ICU)
      because of weaning difficulties (median ventilation, 31 days) had the highest
      mean stay. Nine of the 132 patients had to be transferred to the ICU and 18 died
      while hospitalized (7% of admissions and 13.6% of patients). The patients who
      died were those who were more acutely and severely ill (acute exacerbation in
      home-ventilated patients, patients with acute respiratory failure treated
      initially with non-invasive ventilation and patients transferred from the ICU due
      to weaning difficulties). CONCLUSIONS: Admissions requiring mechanical
      ventilation have increased and most are related to the home mechanical
      ventilation program. The mean stay and the mortality rate were related to the
      reason for admission.

PMID- 11953268
TI  - [The Will-Rogers phenomenon. Stage migration in bronchogenic carcinoma after
      applying certainty criteria].
AB  - OBJECTIVE: To quantify changes in tumor-node-metastasis (TNM) staging (numerical
      migration) and survival (prognostic migration) that arise when certainty criteria
      are applied to a patient population with non-small cell lung cancer (NSCLC)
      treated surgically. METHODS: The population consisted of 1,844 patients with
      NSCLC who underwent surgery between 1993 and 1996 at hospitals participating in
      the Bronchogenic Carcinoma Co-operative Group of the Spanish Society of
      Pneumology and Thoracic Surgery (GCCB-S). For every patient, surgical
      pathological TNM staging (p) was based on two classifications: initial staging by
      each participating GCCB-S center (pTNM-i) and a second classification bearing
      greater classificatory certainty (pTNM-cc) resulting from the application of
      stricter criteria. Numerical migration was said to have occurred in cases where
      the two classifications did not coincide, and the possible prognostic migration
      under the new staging was then assessed. RESULTS: The results revealed great
      numerical migration in the pN0 classification (from 1,091 cases to 665). The
      changes did not result in prognostic migration either for the group as a whole or
      for pT1-2N0M0 cases. However, for pT3N0M0 cases, median survival increased by 13
      months. The difference in three-year survival (S3) for pT3N0M0-i without
      certainty confirmation [S3 = 0.30 (95%CI 0.18-0.42), n=59] and pT3N0M0-cc
      [S3=0.54 (95%CI = 0.44-0.64), n = 92] was significant (log-rank, p = 0.035). Such
      behavior was not observed for pT1-2N0M0. CONCLUSIONS: The numerical migration
      observed as a result of applying surgical-pathological classificatory certainty
      criteria is relevant but the prognostic repercussion is scarce, except in cases
      classified as pT3N0M0, in which a significant positive prognostic migration is
      observed (the "Will Rogers phenomenon").

PMID- 11953269
TI  - [Systemic inflammation during exacerbations of chronic obstructive pulmonary
      disease].
AB  - OBJECTIVE: The circulating blood levels of several inflammatory cytokines and
      acute phase proteins are higher in patients with stable chronic obstructive
      pulmonary disease (COPD). However, whether or not these inflammatory markers
      increase during COPD exacerbation or are modified by corticosteroid treatment has
      not been investigated. The objective of this study was therefore 1) to describe
      changes in several inflammatory markers in systemic circulation during COPD
      exacerbation, and 2) to assess the potential effects of corticosteroid treatment
      during exacerbation. METHODS: Serum levels of tumor necrosis factor-alpha (TNF
      alpha), interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP)
      were determined for 10 patients (65 2 years old) with severe COPD (FEV1 35 4%
      reference) who were hospitalized for acute respiratory failure (PaO2 57 2 mm Hg;
      PaCO2 48 3 mm Hg). Blood samples were obtained in the emergency room (before
      starting intravenous corticosteroid treatment), during the first 24 hours of
      admission, upon discharge and two months later. Eight healthy non-smokers of a
      similar age (54 3 years) were also studied as control subjects. RESULTS: The COPD
      patients had higher concentrations of IL-6 (5.1 1.6 vs. 1.8 0.5 pg/mL, p < 0.05)
      and CRP (2.2 0.4 vs. 0.6 0.2 mg/dL, p < 0.005) than did controls, but the
      concentrations of IL-8 were similar (29 11.3 vs. 34.7 10.3 pg/mL, p = ns). No
      statistically significant changes were seen either during recovery, in spite of
      intravenous corticosteroid treatment, or two months after discharge.The ELISA
      test used was unable to detect TNF-alpha in any of the samples obtained from
      either patients or controls. CONCLUSION: The results show that 1) there is
      evidence of systemic inflammation during exacerbation of COPD, and 2) such
      systemic inflammation does not appear to be influenced significantly by
      intravenous corticosteroid treatment.

PMID- 11953270
TI  - [Venous compression ultrasonography of the lower limbs: a diagnostic tool in the
      hands of pneumologists].
AB  - Our objective was to study agreement between the compression ultrasound images
      taken in our respiratory medicine department and the duplex ultrasound images
      obtained by radiologists at our hospital for patients admitted to our ward with
      suspected diagnoses of venous thromboembolism.Seventy-eight consecutive patients
      admitted to our respiratory medicine ward suspected of venous thromboembolism
      were enrolled. Both types of images were available for all patients studied.
      Agreement was 90% with a Kappa coefficient of 0.81. Agreement between the two
      techniques was good. Therefore, compression ultrasonography is a technique that
      can be handled by respiratory medicine specialists for the diagnosis of venous
      thromboembolism.

PMID- 11953271
TI  - [Respiratory muscles and pulmonary rehabilitation of asthmatics].

PMID- 11953272
TI  - [What should respiratory medicine specialists learn in the years to come?].

PMID- 11953273
TI  - [Therapeutic efficacy of GM-CSF in pulmonary alveolar proteinosis].
AB  - Pulmonary alveolar proteinosis is a rare disease characterized by the deposit of
      lipid-rich proteinaceous material in alveolar spaces. The only effective
      treatment known to date has been periodic alveolar lavage, a technique that is
      laborious and requires that the patient be under general anesthesia, with
      selective endotracheal-bronchial intubation. Complications are not unknown.
      Progress in our understandint of the pathogenesis of pulmonary alveolar
      proteinosis has shown it to be related to changes it to be related to changes in
      alveolar macrophagocytic capability. We describe a patient in whom 8 weeks of
      subdermal GM-CSF treatment led to significant clinical, radiologic and lung
      function improvement.

PMID- 11953274
TI  - [Solitary pulmonary nodule due to Mycobacterium fortuitum].
AB  - We report the case of an asthmatic man in whom a solitary pulmonary nodule was
      discovered after an episode of self-limited hemoptysis. Infection was suspected
      after initial response to empirical antibiotic therapy, and the pathogen was
      later identified to be a rare mycobacterium. The pulmonary nodule resolved
      without surgery after oral quinolone therapy. Mycobacterium fortuitum should be
      added to the list of possible causes of solitary pulmonary nodule in Spain.

PMID- 11953275
TI  - [Arteriovenous pulmonary malformation: have we really made diagnostic progress?].

PMID- 11953276
TI  - [Pulmonary blastoma: an unexpected finding in a woman with polyarthritis].

PMID- 11953277
TI  - [Chylothorax after thoracic sympathectomy by videothorascopy].

PMID- 11953278
TI  - Serum basic fibroblast growth factor levels in exercise-induced myocardial
      ischemia more likely a marker of endothelial dysfunction than a marker of
      ischemia?
AB  - Increased levels and activity of fibroblast growth factor (FGF) have been
      documented in a variety of diseases, including ischemia. Both acute coronary
      syndromes and exercise are situations that stimulate FGF release. Since
      experimental studies have demonstrated that FGFs are involved in myocardial
      preconditioning, it has been suggested that cardiac and circulating FGFs may play
      a cardioprotective role in ischemic diseases. However, the profile of basic FGF
      (bFGF) release during transient myocardial ischemia remains uncertain. We sought
      to determine whether circulating bFGF might be changed in patients with
      demonstrated coronary artery disease and evidence of ischemia in exercise
      scintigraphy (Isch +; n = 21). Serum from 22 age-matched patients with no
      coronary artery disease and no isotopic ischemia (Isch-) were used as controls.
      Three blood samples were obtained to determine bFGF at different times: baseline
      (bFGF-A); maximal exercise (bFGF-B), and isotopic redistribution (bFGF-C). An
      enzyme-linked immunoassay specific for bFGF was used (limit of detection, 1.0
      pg/ml). Circulating bFGF was increased at maximal exercise in both Isch + and
      control patients. However, serum levels of bFGF were elevated up to more than two
      fold in Isch-patients compared to Isch+ patients (8.67 +/- 2.10 pg/ml in Isch+ vs
      17.83 +/- 2.97 pg/ml in Isch- patients; p<0.01). According to previous data,
      these findings suggest that bFGF serum levels could be considered more likely a
      marker of endothelial dysfunction occurring in patients with coronary artery
      disease, rather than a marker of acute ischemia. This situation could be
      different in the clinical setting of chronic myocardial ischemia.

PMID- 11953279
TI  - Influence of mucolytic therapy on respiratory mechanics in patients with chronic
      obstructive pulmonary disease.
AB  - Mucus hypersecretion is a hallmark of chronic obstructive pulmonary disease
      (COPD) and is regarded as contributing to airflow limitation in these patients.
      The value of mucolytic therapy is still a matter for debate. We investigated the
      short-term influence of an inhalative mucolytic drug mercapto-ethane sulfonate
      (Mesna) on the lung function, respiratory mechanics and viscous respiratory load
      in patients with COPD in a randomized, placebo controlled, double-blind, cross
      over study in 10 patients with moderate, stable COPD. Resistance, static
      compliance and frequency dependent dynamic compliance and viscous respiratory
      work, FVC, FEV(1), PEFR, MEF(75), MEF(50), MEF(25), TLC and RV were measured.
      These lung function parameters did not show any significant differences between
      the treatment groups. In conclusion, an inhalative treatment with an active
      mucolytic drug of patients with mild COPD does not improve respiratory mechanics
      and respiratory load.

PMID- 11953280
TI  - Treatment of HIV-associated wasting with recombinant human growth hormone:
      monitoring of body composition changes by bioelectrical impedance analysis (BIA).
AB  - INTRODUCTION: Recombinant human growth hormone (r-hGH) has demonstrated efficacy
      in treating HIV-associated wasting (HAW), however, HAW has become less prominent
      since the introduction of highly active antiretroviral therapy (HAART). Recent
      studies suggest that patients receiving HAART may still experience HAW. We
      investigated the nature of HAW and the efficacy of r-hGH in these patients.
      METHODS: We treated 27 HIV-positive patients receiving HAART who had either
      recent loss of >5% body weight or weight <90% lower limit of normal with 12 weeks
      of r-hGH (6 mg given either daily or every other day). Body composition changes
      were monitored using bioelectrical impedance analysis (BIA). RESULTS were
      assessed for all patients and for a subgroup meeting more stringent definitions
      of wasting (BIA phase angle a<5.6 degrees, n = 14). - RESULTS: Significant
      increases from baseline in weight and body cell mass (BCM) occurred in the full
      population (medians: 2.0 kg weight, 1.5 kg BCM). Patients with phase angle
      alpha<5.6 degrees also showed increases in weight and BCM (medians: 2.5 kg
      weight, 1.95 kg BCM), and 10 of 14 showed improvements in the ratio of
      extracellular mass (ECM) to BCM. At follow-up there was a trend towards loss of
      the weight and BCM gained on treatment. Treatment was well tolerated. CONCLUSION:
      Patients receiving HAART continue to experience wasting, and respond well to r
      hGH therapy as monitored by BIA.

PMID- 11953281
TI  - The generation of oxygen radicals after drinking of oxygenated water.
AB  - It has been speculated whether ingestion of oxygenated water can lead to an
      enhanced generation of oxygen radicals. The purpose of three prospective
      randomized blinded clinical studies was therefore to measure if, when and at
      which oxygen content in the water,drinking of oxygenated water induces the
      generation of radicals. Moreover in the fourth prospective,randomized, blinded
      study possible longterm effects of drinking oxygenated water were examined.
      METHODS: Altogether 66 volunteers were drinking 300 ml oxygenated or tap water
      within 15 minutes. Before drinking, altogether 15 ml of blood from the
      antecubital vein was collected for determination of ascorbyl radicals with ESR,
      routine laboratory data (hemoglobin, erythrocytes, hematocrit, leukocytes,
      thrombocytes, uric acid) and the vitamins A,C,E by HPLC. After drinking the
      ascorbyl radical measurements were repeated from blood of the antecubital vein.
      In the longterm study ( fourth study) the volunteers had to undergo the same
      procedure, as described above, at day 1 and day 21. In the meantime they were
      drinking per day three times 300 ml either oxygenated water or tap water.
      RESULTS: All subjects exhibited normal vitamin levels in all three studies.
      Concommitantly in the fourth study there was no statistically relevant alteration
      of vitamin concentrations during the observation period of three weeks in the
      verum and placebo-group. 30 minutes after drinking oxygenated water the
      concentration of ascorbyl radicals increased significantly by median 42 % from
      median 48 to 65 nmol/l. This increase of ascorbyl radicals after 30 minutes was
      reproducible in all studies. The levels of ascorbyl radicals remained elevated
      for 60 minutes after drinking and returned to normal after 120 minutes. This
      increase was independent of the oxygen concentration in the water, beginning at
      30 mg oxygen/l. Water containing 15 mg oxygen/l did not lead to an enhanced
      radical formation. Longterm consumption of oxygenated water attenuated the
      ascorbyl radical increase normally observed, thus the initial increase of
      ascorbyl radicals at day 1 could not be observed after day 21, if the subjects
      were drinking oxygenated water regularly during the observation period.
      CONCLUSION: Drinking of oxygenated water possibly leads to a time-limited, yet
      very moderate, systemic generation of radicals. Regular consumption of oxygenated
      water over a longer period of time seems to attenuate this effect. The mechanisms
      leading to this effect and adaptation are unknown.

PMID- 11953282
TI  - Intravital fluorescence microscopy and phototocicity: effects on leukocytes.
AB  - The purpose of this investigation was to clarify whether the light exposure of
      fluorescently marked leukocytes and/or plasma influences the leukocyte behavior
      (rolling and firm adhesion). Anaesthetized Balb/c mice were laparotomized to
      expose the mesentery of the terminal ileum. Animals were randomly assigned to 5
      experimental groups. One group was studied in trans-illumination mode, the other
      four groups received iv-bolus injections of either FITC-dextran (FITC-dx) 150 kD,
      rhodamine 6 G (rh6G), a combination of FITC-dx and rh6G, or acridine orange,
      respectively, and were then studied in epi-illumination mode. In each animal,
      eight vessels (6 venules, 2 arterioles) were exposed five times for 60 sec. to
      continuous light of the appropriate excitation wavelength with a 20-min. interval
      between exposures. The vessel diameters and leukocyte-endothelial cell
      interactions were quantified using intravital fluorescence microscopy. The
      diameters of arterioles and postcapillary venules remained unchanged in all
      groups studied. Rolling and adherent leukocytes were observed in postcapillary
      venules only and there were no significant differences between all groups. Under
      these conditions, the exposure of fluorescently labeled leukocytes and/or plasma
      to standard light levels for up to 300 seconds has no significant impact on
      leukocyte-endothelial cell interactions in mesenteric postcapillary venules.

PMID- 11953283
TI  - Brainstem infarctions with normal MRI.
AB  - Most studies on brainstem infarctions included only patients with lesions
      documented by CT or MRI. The aim of this study was to analyse the clinical
      symptomatology in patients with the classical signs of brainstem infarcts and
      normal MRI results. Frequencies of MR-positive and negative infarctions should be
      analysed according to their location. In a series of 30 consecutive patients with
      acute clinical symptoms of ischemic brainstem lesions and persistence of the
      symptomatology for more than 10 days, 8 patients had normal MRI. In these
      patients the location of the lesion was established by clinical and
      electrophysiological criteria. The lesions in the 8 patients with normal MRI were
      situated in medulla oblongata (n=3), in pons (n = 2), and in midbrain (n = 3). In
      each of these patients the clinical symptoms corresponded to one of the classical
      alternating syndromes, which are pathognomic for brainstem infarctions (1
      Wallenberg, 1 Avellis, 1 Jackson, 2 Millard-Gubler, and 3 Weber). The clinical
      course of the infarctions with normal MRI was favourable, the symptoms
      disappeared within few weeks. Our study proved that the clinical diagnosis of
      brainstem infarction, particularly in lesions of midbrain and caudal tegmentum
      pontis, can not be excluded by normal MRI.

PMID- 11953284
TI  - Ocular involvement in Takayasu's arteritis: response to cyclophosphamide therapy.
AB  - PURPOSE: To report a Takayasu's arteritis (TA) case with an intense ocular
      involvement and the response to monthly bolus of Cyclophosphamide. METHODS: Case
      report and literature review. RESULTS: Cyclophosphamide was useful to improve the
      TA symptoms without any additional treatment and any secondary effects. When this
      therapy was discontinued the ocular symptoms progressed. CONCLUSION: Although no
      definitive therapy has been established, Cyclophosphamide intravenous bolus may
      be useful to improve ocular symptoms of Takayasu's Arteritis, specially in early
      stages. There are not adequate descriptions in the literature concerning the
      effect of this treatment on the ocular manifestations of TA.

PMID- 11953285
TI  - Improved procedure of colonoscopy under accompanying music therapy.
AB  - BACKGROUND: Administration of sedatives and analgetics during colonoscopy
      includes the risk for arterial hypotension and respiratory depression. The aim of
      this study was to assess whether music therapy increases patients tolerance and
      reduces the need of analgo-sedative premedication. METHODS: 146 consecutive
      patients were examined in a randomized, prospective study. Colonoscopy was
      performed under intravenous administration with titrated dosages of midazolam and
      pethidin. Oxygen was given in cases of blood desaturation below values of 90%.
      Patients younger than 18 and older than 80 years, patients with history of
      partial colectomy, gastrectomy or hysterectomy and patients with colonic tumorous
      or inflammatory stenosis were excluded. 60 patients underwent conventional
      procedure (Group A), whereas 59 patients received additional music therapy (Group
      B). Time required to reach the cecum (examination time) was measured and the rate
      of successful colonoscopies was determined. RESULTS: Most of the patients
      required sedation with midazolam in both groups (97 vs. 93%), whereas more group
      A patients required analgesia with pethidin than group B patients (43 vs. 31%,
      p<0.05). Under music therapy the rate of completed colonoscopies was higher
      (group A 93%, group B 98%) and examination time was significantly accelerated
      (group A 22.8 +/- 14.6 min, group B 16.8 +/- 11.8 min, p<0.03). CONCLUSIONS:
      Accompanying music therapy reduces requirement of analgesia during colonoscopy,
      favours completion of the procedure and shortens examination time. Music therapy
      seems to promote safer conditions for endoscopical practice and diminishs
      patients discomfort.

PMID- 11953286
TI  - A sebaceous tumor in a patient with acquired immunodeficiency syndrome.
AB  - The prevalence of cutaneous malignancies is higher in immunosuppressed patients.
      Here, we describe a case with a rapid growing and unusually large sebaceous tumor
      in a patient with acquired immunodeficiency syndrome. Sebaceous adenomas are
      commonly rare, benign tumors of sebaceous glands. An association of AIDS and a
      solitary, large sebaceous adenoma has not been described yet. This emphasizes the
      role of an intact immune system in the suppression of benign and malignant
      tumors. tubular adenoma; tumor; AIDS

PMID- 11953289
TI  - "Face-to-face with It": medical students' narratives about their end-of-life
      education.
AB  - Medical schools have been slow to include meaningful end-of-life (EOL)
      educational experiences in their curricula. As an area of inquiry and focused
      clinical experience, death is "conspicuous" by its absence, reflecting a medical
      culture that defines death as failure. The author asked fourth-year medical
      students at one institution to describe their experiences with dying patients and
      their families, the skills and attitudes they brought to these encounters, the
      support they received from attendings and residents while caring for dying
      patients, and suggestions for the medical curriculum that would help prepare them
      for care of the dying. Using a qualitative method, she analyzed ten students'
      written narratives, which dealt with experiences during their third-year
      clerkships, and compared these reflections with the literature on EOL care in
      medical education. The themes that emerged provided four organizers for this
      essay: (1) students' worry and uncertainty about EOL care, (2) guidance and role
      modeling in EOL care, (3) preparation for EOL care, and (4) conclusions and
      recommendations for the medical curriculum. In general, students did not feel
      well prepared or supported as they cared for their first dying patients,
      including, for example, delivering a terminal prognosis or obtaining a DNR.
      However, while they did wish for more support and role modeling from residents
      and attendings, they generally believed that care of the dying can be learned
      only through direct clinical experience. These beliefs call into question
      curricular issues of placement of EOL inquiry--most often in the preclinical
      curriculum--and the teaching of its content, currently overwhelmingly by
      lectures. The author concludes with recommendations for thoughtful, integrative,
      interdisciplinary curriculum changes in EOL education.

PMID- 11953290
TI  - "I learned that no death is routine": description of a death and bereavement
      seminar for pediatrics residents.
AB  - The American Academy of Pediatrics' statement on palliative care for children
      emphasizes the need to identify and address barriers to effective palliative
      care. The authors describe a seminar for pediatrics residents on death and
      bereavement that addresses these issues. The day-long seminar for second-year
      residents has been offered annually since 1996. The seminar is conducted offsite
      so that residents can concentrate without distraction. The seminar uses an
      intense and comprehensive multidisciplinary approach to accomplish seven goals:
      (1) to have residents gain expertise in talking with parents about the death of
      their child; (2) to have residents practice and experience how it feels to be in
      emotionally charged situations; (3) to train residents to become more
      knowledgeable concerning autopsy and organ donation, and to learn strategies to
      approach these topics with a child's parents; (4) to have residents gain an
      understanding of the role of the ministry for families who are grieving; (5) to
      provide residents with multidisciplinary strategies to support a family after a
      child has died; (6) to help residents gain insight into the impact of death on
      their own emotions and the importance of addressing their own emotions to cope
      with stress and potential burnout; (7) and to help residents better understand
      the parents' perceptions of the medical care providers and their dying child. In
      their evaluation comments, the residents report value from a seminar designed to
      help them address issues of patient death and bereavement. This type of
      educational intervention should be considered for the curriculum by other
      residency programs.

PMID- 11953291
TI  - Enhancing palliative care education in medical school curricula: implementation
      of the palliative education assessment tool.
AB  - The authors report the results of a Robert Wood Johnson Foundation-funded project
      that catalyzed New York State medical schools to develop and implement strategic
      plans for curricular change to enhance palliative care education. The project
      used the Palliative Education Assessment Tool for curricular mapping of
      palliative care education throughout each school's four-year curriculum and used
      site visits to facilitate strategic planning within each institution. Of the 14
      New York State medical schools, 13 participated in the project. Ten provided
      strategic plans for change, with a total of 71 specific goals (median = 5 per
      school). Of these goals, 67 (94.4%) had been implemented or were in the active
      planning process one year after the plans were created. Overall, palliative care
      content was enhanced in four curricular areas: basic science courses, ethics and
      humanities courses, clerkship rotations, and faculty development in palliative
      care. The process of self-assessment, curriculum mapping of a specific thematic
      area, and strategic planning for change appears to have successfully enhanced the
      palliative care content in the medical schools' curricula.

PMID- 11953292
TI  - Care at the end of life: a novel curriculum module implemented by medical
      students.
AB  - End-of-life (EOL) and palliative care education in medical school curricula stand
      at a crossroads. Consensus has emerged that these topics merit systematic
      instruction throughout medical school training, yet curricula all too often
      consist of sporadic lectures focused on bioethics instead of clinical skills. The
      medical student authors identified a deficit in their curriculum, and designed
      and implemented an EOL curriculum module for their colleagues. In early 2000 the
      authors surveyed senior medical students about their experiences with EOL and
      palliative education, identifying deficits in clinical training and
      recommendations for interventions. They then designed a case-based educational
      module to teach EOL communication skills to medical students commencing clinical
      training. Faculty with national and local experience with EOL and palliative care
      reviewed the curriculum. Twelve of these faculty were oriented to the curriculum
      and then taught it in pairs to groups of 12 to 16 medical students in 2000 and
      2001. The curriculum develops skills, attitudes, and knowledge relevant for
      communicating bad news and establishing treatment options in the EOL setting by
      utilizing trigger videos, group discussion, role plays, and case discussions.
      Approximately 75% of the 86 eligible students attended the module in 2000 and
      2001. Feedback has guided the curriculum's refinement by the medical student
      authors. In addition, a standardized patient exercise, introduced in 2001,
      allowed students to reinforce the skills learned during the module.

PMID- 11953294
TI  - ACGME requirements for end-of-life training in selected residency and fellowship
      programs: a status report.
AB  - INTRODUCTION: National recommendations have been developed for physicians' end-of
      life (EOL) education. No comprehensive assessment has been done to examine
      postgraduate (residency and fellowship) EOL training. METHOD: The authors
      reviewed the EOL content for 46 specialties in postgraduate training programs
      that affect the care of seriously ill and dying patients, using data from the
      2000/2001 AMA Graduate Medical Education Directory. RESULTS: Internal medicine,
      geriatrics, and neurology contained the most comprehensive EOL requirements. Most
      surgical specialties contained no EOL requirement except ethics. Ethics (n = 25)
      and psychosocial care (n = 22) were the most common EOL domains mandated,
      although specific EOL content was not specified. Training in EOL communication (n
      = 1), personal awareness (n = 3), and EOL clinical experiences (n = 5) were the
      least often required instructional domains. Instruction in pain assessment and
      management was required in only one surgical specialty. CONCLUSIONS: The lack of
      comprehensive EOL training requirements may help explain the known problems in
      physicians' EOL care. Major reform in EOL requirements is needed at the level of
      residency review committees.

PMID- 11953295
TI  - Physicians' ratings of their knowledge, attitudes, and end-of-life-care
      practices.
AB  - PURPOSE: Health care institutions are examining ways to improve physicians'
      skills in the delivery of end-of-life (EOL) care. Experts have suggested that
      influencing physicians' knowledge and attitudes concerning EOL care can influence
      subsequent EOL practices, including hospice use for appropriate patients; yet few
      studies have examined empirically the influence of physicians' knowledge and
      attitudes on such practices. The authors assessed the influences of self-rated
      knowledge and attitudes on physicians' discussions and referrals for hospice
      care. METHOD: In 1998 and 1999 the authors conducted a cross-sectional study of
      physicians affiliated with six randomly selected community hospitals in
      Connecticut with more than 200 licensed medical and surgical beds. Physicians
      completed a self-administered questionnaire (response rate 52.4%) that assessed
      self-rated knowledge of terminal care and hospice, a set of attitudinal items,
      and practices related to hospice discussion and referrals, as well as standard
      sociodemographic data. Bivariate and multivariate analyses were conducted.
      RESULTS: Self-rated knowledge was significantly associated with referral
      practices in unadjusted analyses (unadjusted odds ratio [OR]: 0.70; 95%
      confidence interval [CI]: 0.52, 0.95), although this association was attenuated
      in adjusted analyses by specialty and other physicians' characteristics (adjusted
      OR: 0.80; 95% CI: 0.55, 1.18). Attitudes representing support for hospice
      practices and philosophy were associated with referral practices in adjusted and
      unadjusted analyses (adjusted OR:0.52; 95% CI: 0.35, 0.77). CONCLUSIONS: This
      study demonstrated that self-rated knowledge and attitudes may influence hospice
      referral. The results support current efforts to develop medical school curricula
      and continuing education programs that better cover the many aspects of caring
      for the dying, including hospice use.

PMID- 11953296
TI  - The more things change: revisiting a comparison of educational costs and incomes
      of physicians and other professionals.
AB  - The authors previously compared the 1990 educational costs and incomes of
      physicians and other professional groups. Since then, there have been dramatic
      changes in the market for the groups examined. This article reports their update
      of the previous analysis, using 1997 data. For this update, the authors applied
      standard financial techniques to expected incomes and educational costs to
      determine the return on educational investment over the working lifetime for five
      professional groups: primary care physicians, procedure-based physicians,
      dentists, attorneys, and graduates of the top 20 business schools. The hours
      adjusted net present values of the educational investments for attorneys ($10.73)
      and procedure-based physicians ($10.40) are considerably higher than those for
      dentists ($8.90) and businessmen ($8.27); the return for primary care physicians
      ($5.97) remains much lower than all others. Primary care physicians have an hours
      adjusted internal rate of return on their educational investment equal to 16%,
      compared with 18% for procedure-based medicine, 22% for dentistry, 23% for law,
      and 26% for business. Although it remains the lowest of all professional groups
      examined, primary care medicine has made the largest percentage gain in net
      present value of all groups. Although anticipated changes in physician incomes
      have occurred, the standing of physicians relative to other professional groups
      has not changed. Students can still anticipate relatively poorer returns on their
      educational investment when they choose a career in primary care medicine as
      compared with careers in procedure-based medicine or surgical specialties,
      business, law, or dentistry.

PMID- 11953297
TI  - The precarious position of the medical humanities in the medical school
      curriculum.
AB  - The author contends that bioethics, as currently conceived and taught in most
      medical schools across the country, should neither be considered as part of nor
      substituted for the humanities within the curriculum. Arguing that bioethics has
      evolved into a discipline dominated by rules--which has tilted it more toward
      scientific methods of reasoning--the author asserts that literature and the fine
      arts maintain a more humanistic approach rather than focusing on abstract
      principles. Consequently, the medical humanities and bioethics represent valuable
      but distinctly different ways of analyzing information, viewing the world,
      confronting dilemmas, and teaching students. The author stresses both the
      affective and the cognitive skills gained from incorporating the humanities
      formally within a medical education environment and shows how including
      literature and the fine arts emphasizes medicine as a profession rather than
      merely a trade. Incorporating these disciplines legitimizes individual
      questioning and collective probing that, in turn, motivate practitioners and
      students to confront fundamental questions about both their chosen field and
      their particular places within it. Thus, within the required educational
      curriculum structured discussions exploring a broad range of medical humanities
      can play a crucial role that can be neither emulated nor replicated by studying
      bioethics. Including the medical humanities as part of health care professional's
      basic training remains pivotal in helping to shape his or her future, both as a
      compassionate practitioner and as a reflective human being.

PMID- 11953298
TI  - How do physicians teach empathy in the primary care setting?
AB  - To explore how primary care clinician-teachers actually attempt to convey empathy
      to medical students and residents, the author carried out a qualitative study in
      1999-2000 in which 12 primary care physicians reflected on their views of
      empathy, how they demonstrated empathy to patients, and how they went about
      teaching empathy to learners. Interview data were triangulated with observations
      of actual teaching sessions and informal questioning of students and residents
      who had been taught by the faculty participants. Grounded theory was used to
      interpret the data. The faculty had clear conceptualizations of what empathy
      meant in clinical practice, but differed as to whether it was primarily a
      measurable, behavioral skill or a global attitude. Respondents stressed the
      centrality of role modeling in teaching, and most used debriefing strategies, as
      well as both learner- and patient-centered approaches, in instructing learners
      about empathy. Findings suggest that limiting the teaching of empathy to a skill
      based approach does not reflect the richness of what actually occurs in the
      clinical setting, and that it is important to teach empathy comprehensively,
      acknowledging both behavioral and attitudinal tools.

PMID- 11953302
TI  - The impacts of supervision, patient mix, and numbers of students on the
      effectiveness of clinical rotations.
AB  - PURPOSE: This study investigated whether supervision, patient mix, and numbers of
      students influence the effectiveness of clinical rotations. METHOD: The authors
      administered a questionnaire to 1,208 medical students in 1999 to evaluate the
      rotations' quality. They computed four variables--overall effectiveness,
      supervision, patient mix, and number of students contemporaneously involved--and
      analyzed the data using analysis of variance. RESULTS: Supervision and patient
      mix positively influenced a rotation's effectiveness. A higher level of
      supervision and a higher level of patient mix led to higher overall effectiveness
      scores. The number of students did not significantly influence the effectiveness
      score, although a low number led to a higher score as compared with a high
      number. Furthermore, the two-way interaction between supervision and patient mix
      was significant. Supervision more strongly influenced the rotation's
      effectiveness when patient mix was limited than when it was high. Also, when the
      patient mix was limited and supervision was high, the average effectiveness score
      was still 7.7 (scale 1-10). CONCLUSIONS: The effectiveness of clinical rotations
      depends on the supervision provided and patient mix, but not the number of
      students. Furthermore, supervision more strongly influences effectiveness when
      patient mix is limited than when it is high. Finally, high-quality supervision
      guarantees at least a sufficient score for the rotation's effectiveness,
      irrespective of the level of patient mix.

PMID- 11953303
TI  - The determinants of attitudinal change among medical students participating in
      home care training: a multi-center study.
AB  - PURPOSE: To report attitudinal changes of medical students from five medical
      schools rotating through a home care program, and to determine which of the
      program characteristics influenced attitudes the most. METHOD: A survey
      instrument covering four home care domains (general attitudes, home-based
      therapies, home care training, and time and reimbursement) was designed and
      validated by the five schools involved. Using pre- and post-rotation scores,
      analyses were done to evaluate for attitudinal changes within and among schools.
      The programs had similar basic characteristics (home visits, attending
      physicians' involvement, didactics), but had differing degrees of these
      components. RESULTS: Significant improvements in attitude scores were found in
      three domains: general attitudes, homebased therapies, and home care training.
      For time and reimbursement, only three schools improved significantly between pre
      and post-rotation scores. Among the five schools, there were significant
      differences in the homebased therapies and home care training domains (p <.05),
      and in the time and reimbursement domain the difference approached significance
      (p =.06). None of the students' characteristics but all of the programs'
      characteristics significantly correlated with changes in total scores. In the
      first multiple regression model, educational level (third year instead of fourth)
      was the only independent predictor of change in score, (adjusted r(2) =.14). In
      Model 2, the strongest predictor was "contact with physician-program director,"
      followed by "number of visits" and "physician-precepted visits" (r(2) =.23).
      CONCLUSION: Educational home care programs of varying intensities can positively
      affect medical students' attitudes towards home care. At least three program
      characteristics, (the physician-program director, number of visits, and physician
      precepted home visits), are important parts of a successful program.

PMID- 11953304
TI  - Can medical school admission committee members predict which applicants will
      choose primary care careers?
AB  - PURPOSE: To determine the accuracy of admission committee members' predictions
      regarding which applicants are likely to become generalists, and to determine
      which applicant characteristics are used and should be used in making these
      predictions. METHOD: Thirteen characteristics of each applicant who entered
      medical school in 1990-1993 and graduated in 1994-1997 were obtained from their
      applications. Committee members reviewed these characteristics and assigned a
      probability of each applicant's choosing a generalist career. Just before their
      graduation, the students were surveyed to ascertain their career plans. The
      relationships between the characteristics and career predictions were analyzed
      using regression models. A secondary analysis examined the relationship between
      the students' stated career preferences at matriculation and career plans at
      graduation. RESULTS: The accuracy of the committee members' predictions was low.
      Predictions of generalist careers were significantly related to seven applicant
      characteristics: rural legal residence, gender (women), lower science grades,
      lower MCAT science scores, lower levels of parents' education, no reported
      research activity, and higher levels of community service. In contrast, the
      students' actual generalist career plans at graduation were significantly related
      only to gender (women) and higher levels of community service. In the secondary
      analysis, applicants' stated career preferences at matriculation were the
      strongest predictor of their having generalist career plans at graduation.
      CONCLUSIONS: Admission committee members often made inaccurate predictions about
      applicants' career plans. This may be because they based their judgments on
      applicants' characteristics that were not significantly related to the students'
      career plans at graduation.

PMID- 11953305
TI  - Natural history of knowledge deficiencies following clerkships.
AB  - PURPOSE: To determine the prognosis of failing a clerkship final examination.
      METHOD: From 1994-99, 48 students at the Uniformed Services University of the
      Health Sciences (6%) failed the end-of-clerkship National Board of Medical
      Examiners' (NBME) subject exam, but otherwise had acceptable medicine clerkship
      performances. All of these students were retested after self-directed study;
      those who failed the retest were prescribed fourth-year medicine before a second
      retest. The authors compared median NBME subject exam scores and number of weeks
      of self-directed study time from the initial exam to the retest for those who
      passed and those who failed the retest. RESULTS: 40 students (83%) passed and
      eight students (17%) failed the first retest. There was no difference between the
      initial median NBME score (303 versus 295, p = ns) or length of self-directed
      study time (25 weeks versus 18 weeks, p = ns) between those who passed and failed
      the retest, respectively. After fourth-year medicine, all eight students passed
      the second retest of the subject exam. Four of the 48 students failed USMLE Step
      2. Compared with those who passed Step 2, these four students had a similar
      median initial NBME subject exam score (293 versus 291, p = ns), but had a lower
      median retest exam score (354 versus 405, p = ns). CONCLUSIONS: It appears
      reasonable to allow students with isolated knowledge deficiencies one attempt to
      retake a failed clerkship exam following a period of self-directed study.
      Confirmatory studies are needed.

PMID- 11953306
TI  - Health professions students' perceptions of interprofessional relationships.
AB  - PURPOSE: To make a preliminary assessment of the perceptions of health
      professions students about interprofessional cooperation. METHOD: Health
      professions students (588 students from eight professions) at the Iowa Geriatric
      Education Center's partner institutions received a questionnaire of demographics
      questions and the Interdisciplinary Education Perception Scale (IEPS). The IEPS
      is an 18-item questionnaire that uses a six-point Likert-type scale to measure
      attitudes toward interprofessional cooperation on four factors: competence and
      autonomy, perceived need for cooperation, perception of actual cooperation, and
      understanding others' value. RESULTS: Total mean IEPS scores differed
      significantly among professional groups (p =.001), with physician assistant
      students scoring highest (most positive attitudes) and chiropractic students
      scoring lowest. The medical students' mean total score was significantly lower
      than was that of physician assistant students (p =.003) and higher than was that
      of chiropractic students (p =.000), but medical students' scores did not differ
      significantly at the alpha =.05 level from those of osteopathy, physical therapy,
      nursing, podiatry, or social work students. CONCLUSION: This study provides the
      first normative data for the IEPS for students from these eight health
      professions. This instrument may be valuable when designing an evaluation scheme
      for training programs that have interdisciplinary components, which may be
      increasingly prevalent in the future.

PMID- 11953307
TI  - Life without transcriptional control? From fly to man and back again.

PMID- 11953308
TI  - 14-3-3 amplifies and prolongs adrenergic stimulation of HERG K+ channel activity.
AB  - Acute stress provokes lethal cardiac arrhythmias in the hereditary long QT
      syndrome. Here we provide a novel molecular mechanism linking beta-adrenergic
      signaling and altered human ether-a-go-go related gene (HERG) channel activity.
      Stress stimulates beta-adrenergic receptors, leading to cAMP elevations that can
      regulate HERG K+ channels both directly and via phosphorylation by cAMP-dependent
      protein kinase (PKA). We show that HERG associates with 14-3-3epsilon to
      potentiate cAMP/PKA effects upon HERG. The binding of 14-3-3 occurs
      simultaneously at the N- and C-termini of the HERG channel. 14-3-3 accelerates
      and enhances HERG activation, an effect that requires PKA phosphorylation of HERG
      and dimerization of 14-3-3. The interaction also stabilizes the lifetime of the
      PKA-phosphorylated state of the channel by shielding the phosphates from cellular
      phosphatases. The net result is a prolongation of the effect of adrenergic
      stimulation upon HERG activity. Thus, 14-3-3 interactions with HERG may provide a
      unique mechanism for plasticity in the control of membrane excitability and
      cardiac rhythm.

PMID- 11953309
TI  - TCR signal initiation machinery is pre-assembled and activated in a subset of
      membrane rafts.
AB  - Recent studies suggest that rafts are involved in numerous cell functions,
      including membrane traffic and signaling. Here we demonstrate, using a
      polyoxyethylene ether Brij 98, that detergent-insoluble microdomains possessing
      the expected biochemical characteristics of rafts are present in the cell
      membrane at 37 degrees C. After extraction, these microdomains are visualized as
      membrane vesicles with a mean diameter of approximately 70 nm. These findings
      provide further evidence for the existence of rafts under physiological
      conditions and are the basis of a new isolation method allowing more accurate
      analyses of raft structure. We found that main components of T cell receptor
      (TCR) signal initiation machinery, i.e. TCR-CD3 complex, Lck and ZAP-70 kinases,
      and CD4 co-receptor are constitutively partitioned into a subset of rafts.
      Functional studies in both intact cells and isolated rafts showed that upon
      ligation, TCR initiates the signaling in this specialized raft subset. Our data
      thus strongly indicate an important role of rafts in organizing TCR early
      signaling pathways within small membrane microdomains, both prior to and
      following receptor engagement, for efficient TCR signal initiation upon
      stimulation.

PMID- 11953310
TI  - The Hrp pilus of Pseudomonas syringae elongates from its tip and acts as a
      conduit for translocation of the effector protein HrpZ.
AB  - The type III secretion system (TTSS) is an essential requirement for the
      virulence of many Gram-negative bacteria infecting plants, animals and man.
      Pathogens use the TTSS to deliver effector proteins from the bacterial cytoplasm
      to the eukaryotic host cell, where the effectors subvert host defences. Plant
      pathogens have to translocate their effector proteins through the plant cell wall
      barrier. The best candidates for directing effector protein traffic are bacterial
      appendages attached to the membrane-bound components of the TTSS. We have
      investigated the protein secretion route in relation to the TTSS appendage,
      termed the Hrp pilus, of the plant pathogen Pseudomonas syringae pv. tomato. By
      pulse expression of proteins combined with immunoelectron microscopy, we show
      that the Hrp pilus elongates by the addition of HrpA pilin subunits at the distal
      end, and that the effector protein HrpZ is secreted only from the pilus tip. Our
      results indicate that both HrpA and HrpZ travel through the Hrp pilus, which
      functions as a conduit for the long-distance translocation of effector proteins.

PMID- 11953311
TI  - VDAC and the bacterial porin PorB of Neisseria gonorrhoeae share mitochondrial
      import pathways.
AB  - The human pathogen Neisseria gonorrhoeae induces host cell apoptosis during
      infection by delivering the outer membrane protein PorB to the host cell's
      mitochondria. PorB is a pore-forming beta-barrel protein sharing several features
      with the mitochondrial voltage-dependent anion channel (VDAC), which is involved
      in the regulation of apoptosis. Here we show that PorB of pathogenic Neisseria
      species produced by host cells is efficiently targeted to mitochondria. Imported
      PorB resides in the mitochondrial outer membrane and forms multimers with similar
      sizes as in the outer bacterial membrane. The mitochondria completely lose their
      membrane potential, a characteristic previously observed in cells infected with
      gonococci or treated with purified PorB. Closely related bacterial porins of non
      pathogenic Neisseria mucosa or Escherichia coli remain in the cytosol. Import of
      PorB into mitochondria in vivo is independent of a linear signal sequence.
      Insertion of PorB into the mitochondrial outer membrane in vitro depends on the
      activity of Tom5, Tom20 and Tom40, but is independent of Tom70. Our data show
      that human VDAC and bacterial PorB are imported into mitochondria by a similar
      mechanism.

PMID- 11953312
TI  - A photosystem II-associated carbonic anhydrase regulates the efficiency of
      photosynthetic oxygen evolution.
AB  - We show for the first time that Cah3, a carbonic anhydrase associated with the
      photosystem II (PSII) donor side in Chlamydomonas reinhardtii, regulates the
      water oxidation reaction. The mutant cia3, lacking Cah3 activity, has an impaired
      water splitting capacity, as shown for intact cells, thylakoids and PSII
      particles. To compensate this impairment, the mutant overproduces PSII reaction
      centres (1.6 times more than wild type). We present compelling evidence that the
      mutant has an average of two manganese atoms per PSII reaction centre. When
      bicarbonate is added to mutant thylakoids or PSII particles, the O2 evolution
      rates exceed those of the wild type by up to 50%. The donor side of PSII in the
      mutant also exhibits a much higher sensitivity to overexcitation than that of the
      wild type. We therefore conclude that Cah3 activity is necessary to stabilize the
      manganese cluster and maintain the water-oxidizing complex in a functionally
      active state. The possibility that two manganese atoms are enough for water
      oxidation if bicarbonate ions are available is discussed.

PMID- 11953313
TI  - Conditional switching of VEGF provides new insights into adult neovascularization
      and pro-angiogenic therapy.
AB  - To gain insight into neovascularization of adult organs and to uncover inherent
      obstacles in vascular endothelial growth factor (VEGF)-based therapeutic
      angiogenesis, a transgenic system for conditional switching of VEGF expression
      was devised. The system allows for a reversible induction of VEGF specifically in
      the heart muscle or liver at any selected schedule, thereby circumventing
      embryonic lethality due to developmental misexpression of VEGF. Using this
      system, we demonstrate a progressive, unlimited ramification of the existing
      vasculature. In the absence of spatial cues, however, abnormal vascular trees
      were produced, a consequence of chaotic connections with the existing network and
      formation of irregularly shaped sac-like vessels. VEGF also caused a massive and
      highly disruptive edema. Importantly, premature cessation of the VEGF stimulus
      led to regression of most acquired vessels, thus challenging the utility of
      therapeutic approaches relying on short stimulus duration. A critical transition
      point was defined beyond which remodeled new vessels persisted for months after
      withdrawing VEGF, conferring a long-term improvement in organ perfusion. This
      novel genetic system thus highlights remaining problems in the implementation of
      pro-angiogenic therapy.

PMID- 11953314
TI  - A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular
      domain and regulates disassembly of adherens junctions.
AB  - E-cadherin controls a wide array of cellular behaviors including cell-cell
      adhesion, differentiation and tissue development. Here we show that presenilin-1
      (PS1), a protein involved in Alzheimer's disease, controls a gamma-secretase-like
      cleavage of E-cadherin. This cleavage is stimulated by apoptosis or calcium
      influx and occurs between human E-cadherin residues Leu731 and Arg732 at the
      membrane-cytoplasm interface. The PS1/gamma-secretase system cleaves both the
      full-length E-cadherin and a transmembrane C-terminal fragment, derived from a
      metalloproteinase cleavage after the E-cadherin ectodomain residue Pro700. The
      PS1/gamma-secretase cleavage dissociates E-cadherins, beta-catenin and alpha
      catenin from the cytoskeleton, thus promoting disassembly of the E-cadherin
      catenin adhesion complex. Furthermore, this cleavage releases the cytoplasmic E
      cadherin to the cytosol and increases the levels of soluble beta- and alpha
      catenins. Thus, the PS1/gamma-secretase system stimulates disassembly of the E
      cadherin- catenin complex and increases the cytosolic pool of beta-catenin, a key
      regulator of the Wnt signaling pathway.

PMID- 11953315
TI  - The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation
      of alpha(v)beta3 integrins.
AB  - Central nervous system development requires precise and localized regulation of
      neural precursor behaviour. Here we show how the interaction between growth
      factor and integrin signalling pathways provides a mechanism for such precision
      in oligodendrocyte progenitor (OP) proliferation. While physiological
      concentrations of platelet-derived growth factor (PDGF) were not in themselves
      sufficient to promote OP proliferation, they did so on extracellular matrix (ECM)
      substrates that bind alpha(v)beta3 integrin. Upon PDGF-AA exposure and
      alpha(v)beta3 engagement, a physical co-association between both receptors was
      demonstrated, confirming the interaction between these signalling pathways.
      Furthermore, we found that PDGFalphaR stimulated a protein kinase C-dependent
      activation of integrin alpha(v)beta3, which in turn induced OP proliferation via
      a phosphatidylinositol 3-kinase-dependent signalling pathway. These studies
      establish a mechanism by which OP proliferation is dependent on the availability
      of both an ECM ligand and a mitogenic growth factor. Growth factor- mediated
      integrin activation is the critical integrative step in proliferation signalling,
      and ensures that the response of neural precursor cells to long-range cues can be
      regulated by their cellular neighbours, allowing precise control of cell
      behaviour during development.

PMID- 11953317
TI  - Interferon-gamma-induced chromatin remodeling at the CIITA locus is BRG1
      dependent.
AB  - SWI/SNF regulates growth control, differentiation and tumor suppression, yet few
      direct targets of this chromatin-remodeling complex have been identified in
      mammalian cells. We report that SWI/SNF is required for interferon (IFN)-gamma
      induction of CIITA, the master regulator of major histocompatibility complex
      class II expression. Despite the presence of functional STAT1, IRF-1 and USF-1,
      activators implicated in CIITA expression, IFN-gamma did not induce CIITA in
      cells lacking BRG1 and hBRM, the ATPase subunits of SWI/SNF. Reconstitution with
      BRG1, but not an ATPase-deficient version of this protein (K798R), rescued CIITA
      induction, and enhanced the rate of induction of the IFN-gamma-responsive GBP-1
      gene. Not ably, BRG1 inhibited the CIITA promoter in transient transfection
      assays, underscoring the importance of an appropriate chromosomal environment.
      Chromatin immunoprecipitation revealed that BRG1 interacts directly with the
      endogenous CIITA promoter in an IFN-gamma-inducible fashion, while in vivo DNase
      I footprinting and restriction enzyme accessibility assays showed that chromatin
      remodeling at this locus requires functional BRG1. These data provide the first
      link between a cytokine pathway and SWI/SNF, and suggest a novel role for this
      chromatin-remodeling complex in immune surveillance.

PMID- 11953316
TI  - Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic
      chromatin condensation.
AB  - To study the role of caspase-6 during nuclear disassembly, we generated a chicken
      DT40 cell line in which both alleles of the caspase-6 gene were disrupted. No
      obvious morphological differences were observed in the apoptotic process in
      caspase-6- deficient cells compared with the wild type. However, examination of
      apoptosis in a cell-free system revealed a block in chromatin condensation and
      apoptotic body formation when nuclei from HeLa cells expressing lamin A or lamin
      A-transfected Jurkat cells were incubated in caspase-6-deficient apoptotic
      extracts. Transfection of exogenous caspase-6 into the clone reversed this
      phenotype. Lamins A and C, which are caspase-6-only substrates, were cleaved by
      the wild-type and heterozygous apoptotic extracts but not by the extracts lacking
      caspase-6. Furthermore, the caspase-6 inhibitor z-VEID-fmk mimicked the effects
      of caspase-6 deficiency and prevented the cleavage of lamin A. Taken together,
      these observations indicate that caspase-6 activity is essential for lamin A
      cleavage and that when lamin A is present it must be cleaved in order for the
      chromosomal DNA to undergo complete condensation during apoptotic execution.

PMID- 11953318
TI  - Solution structure of the LicT-RNA antitermination complex: CAT clamping RAT.
AB  - LicT is a bacterial regulatory protein able to prevent the premature arrest of
      transcription. When activated, LicT binds to a 29 base RNA hairpin overlapping a
      terminator located in the 5' mRNA leader region of the target genes. We have
      determined the solution structure of the LicT RNA-binding domain (CAT) in complex
      with its ribonucleic antiterminator (RAT) target by NMR spectroscopy (PDB 1L1C).
      CAT is a beta-stranded homodimer that undergoes no important conformational
      changes upon complex formation. It interacts, through mostly hydrophobic and
      stacking interactions, with the distorted minor groove of the hairpin stem that
      is interrupted by two asymmetric internal loops. Although different in sequence,
      these loops share sufficient structural analogy to be recognized similarly by
      symmetry-related elements of the protein dimer, leading to a quasi- symmetric
      structure reminiscent of that observed with dimeric transcription regulators
      bound to palindromic DNA. Sequence analysis suggests that this RNA- binding mode,
      where the RAT strands are clamped by the CAT dimer, is conserved in homologous
      systems.

PMID- 11953319
TI  - Exploring intracellular space: function of the Min system in round-shaped
      Escherichia coli.
AB  - The MinCDE proteins help to select cell division sites in normal cylindrical
      Escherichia coli by oscillating along the long axis, preventing unwanted polar
      divisions. To determine how the Min system might function in cells with multiple
      potential division planes, we investigated its role in a round-cell rodA mutant.
      Round cells lacking MinCDE were viable, but growth, morphology and positioning of
      cell division sites were abnormal relative to Min+ cells. In round cells with a
      long axis, such as those undergoing cell division, green fluorescent protein
      (GFP) fusions to MinD almost always oscillated parallel to the long axis.
      However, perfect spheres or irregularly shaped cells exhibited MinD movement to
      and from multiple sites on the cell surface. A MinE-GFP fusion exhibited similar
      behavior. These results indicate that the Min proteins can potentially localize
      anywhere in the cell but tend to move a certain maximum distance from their
      previous assembly site, thus favoring movement along the cell's long axis. A new
      model for the spatial control of division planes by the Min system in round cells
      is proposed.

PMID- 11953320
TI  - Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-mediated
      phosphorylation.
AB  - Cell cycle progression in eukaryotes is mediated by phosphorylation of protein
      substrates by the cyclin-dependent kinases (CDKs). We screened a cDNA library by
      solid-phase phosphorylation and isolated hHR6A as a CDK2 substrate. hHR6A is the
      human homologue of the product of the Saccharomyces cerevisiae RAD6/UBC2 gene, a
      member of the family of ubiquitin-conjugating enzymes. hHR6A is phosphorylated in
      vitro by CDK-1 and -2 on Ser120, a residue conserved in all hHR6A homologues,
      resulting in a 4-fold increase in its ubiquitin-conjugating activity. In vivo,
      hHR6A phosphorylation peaks during the G2/M phase of cell cycle transition, with
      a concomitant increase in histone H2B ubiquitylation. Mutation of Ser120 to
      threonine or alanine abolished hHR6A activity, while mutation to aspartate to
      mimic phosphorylated serine increased hHR6A activity 3-fold. Genetic
      complementation studies in S.cerevisiae demonstrated that hHR6A Ser120 is
      critical for cellular proliferation. This is the first study to demonstrate
      regulation of UBC function by phosphorylation on a conserved residue and suggests
      that CDK-mediated phosphorylation of hHR6A is an important regulatory event in
      the control of cell cycle progression.

PMID- 11953321
TI  - Saccharomyces cerevisiae MGS1 is essential in strains deficient in the RAD6
      dependent DNA damage tolerance pathway.
AB  - Saccharomyces cerevisiae Mgs1 protein, which possesses DNA-dependent ATPase and
      single strand DNA annealing activities, plays a role in maintaining genomic
      stability. We found that mgs1 is synthetic lethal with rad6 and exhibits a
      synergistic growth defect with rad18 and rad5, which are members of the RAD6
      epistasis group important for tolerance of DNA damage during DNA replication. The
      mgs1 mutant is not sensitive to DNA-damaging agents, but the mgs1 rad5 double
      mutant has increased sensitivity to hydroxyurea and a greatly increased
      spontaneous mutation rate. Growth defects of mgs1 rad18 double mutants are
      suppressed by a mutation in SRS2, encoding a DNA helicase, or by overexpression
      of Rad52. More over, mgs1 mutation suppresses the temperature sensitivity of
      mutants in POL3, encoding DNA polymerase delta. mgs1 also suppresses the growth
      defect of a pol3 mutant caused by expression of Escherichia coli RuvC, a
      bacterial Holliday junction resolvase. These findings suggest that Mgs1 is
      essential for preventing genome instability caused by replication fork arrest in
      cells deficient in the RAD6 pathway and may modulate replication fork movement
      catalyzed by yeast polymerase delta.

PMID- 11953322
TI  - Nuclear dynamics of RAD52 group homologous recombination proteins in response to
      DNA damage.
AB  - Recombination between homologous DNA molecules is essential for the proper
      maintenance and duplication of the genome, and for the repair of exogenously
      induced DNA damage such as double-strand breaks. Homologous recombination
      requires the RAD52 group proteins, including Rad51, Rad52 and Rad54. Upon
      treatment of mammalian cells with ionizing radiation, these proteins accumulate
      into foci at sites of DNA damage induction. We show that these foci are dynamic
      structures of which Rad51 is a stably associated core component, whereas Rad52
      and Rad54 rapidly and reversibly interact with the structure. Furthermore, we
      show that the majority of the proteins are not part of the same multi-protein
      complex in the absence of DNA damage. Executing DNA transactions through dynamic
      multi-protein complexes, rather than stable holo-complexes, allows flexibility.
      In the case of DNA repair, for example, it will facilitate cross-talk between
      different DNA repair pathways and coupling to other DNA transactions, such as
      replication.

PMID- 11953323
TI  - Specific interaction of IP6 with human Ku70/80, the DNA-binding subunit of DNA
      PK.
AB  - In eukaryotic cells, DNA double-strand breaks can be repaired by non-homologous
      end-joining, a process dependent upon Ku70/80, XRCC4 and DNA ligase IV. In
      mammals, this process also requires DNA-PK(cs), the catalytic subunit of the DNA
      dependent protein kinase DNA-PK. Previously, inositol hexakisphosphate (IP6) was
      shown to be bound by DNA-PK and to stimulate DNA-PK-dependent end-joining in
      vitro. Here, we localize IP6 binding to the Ku70/80 subunits of DNA- PK, and show
      that DNA-PK(cs) alone exhibits no detectable affinity for IP6. Moreover,
      proteolysis mapping of Ku70/80 in the presence and absence of IP6 indicates that
      binding alters the conformation of the Ku70/80 heterodimer. The yeast homologue
      of Ku70/80, yKu70/80, fails to bind IP6, indicating that the function of IP6 in
      non-homologous end-joining, like that of DNA-PK(cs), is unique to the mammalian
      end-joining process.

PMID- 11953324
TI  - The active site of the DNA repair endonuclease XPF-ERCC1 forms a highly conserved
      nuclease motif.
AB  - XPF-ERCC1 is a structure-specific endonuclease involved in nucleotide excision
      repair, interstrand crosslink repair and homologous recombination. So far, it has
      not been shown experimentally which subunit of the heterodimer harbors the
      nuclease activity and which amino acids contribute to catalysis. We used an
      affinity cleavage assay and located the active site to amino acids 670-740 of
      XPF. Point mutations generated in this region were analyzed for their role in
      nuclease activity, metal coordination and DNA binding. Several acidic and basic
      residues turned out to be required for nuclease activity, but not DNA binding.
      The separation of substrate binding and catalysis by XPF-ERCC1 will be invaluable
      in studying the role of this protein in various DNA repair processes. Alignment
      of the active site region of XPF with proteins belonging to the Mus81 family and
      a putative archaeal RNA helicase family reveals that seven of the residues of XPF
      involved in nuclease activity are absolutely conserved in the three protein
      families, indicating that they share a common nuclease motif.

PMID- 11953325
TI  - Host-pathogen interactions: the seduction of molecular cross talk.
AB  - Bacterial pathogens have evolved two major strategies to colonise the intestinal
      epithelium. Adherent microorganisms bind to the apical pole of the intestinal
      epithelium, whereas invasive microorganisms disrupt and invade the epithelium.
      Recognition of the genetic bases of bacterial pathogenicity and analysis of the
      molecular cross talks established between pathogens and their mammalian target
      cells have illuminated this diversity of interactions. We have compared the
      strategies of enteroinvasive pathogens, with emphasis on bacterial species such
      as Shigella, Yersinia, and Salmonella, that represent paradigms of interaction.
      Cross talks leading to alteration of the epithelial cell actin cytoskeleton
      appear as a recurrent theme during entry and dissemination into epithelial cells.
      Other cross talks alter the trafficking of cellular vesicles and induce changes
      in the intracellular compartment in which they reside, thus creating niches
      favourable to bacterial survival and growth. Finally, a variety of strategies
      also exist to deal with other components of the epithelial barrier, such as
      macrophages. Pro-phagocytic, anti-phagocytic, and pro-apoptotic processes appear
      to be of particular importance.

PMID- 11953326
TI  - Toxins and the gut: role in human disease.
AB  - Bacterial enteric infections exact a heavy toll on the human population,
      particularly among children. Despite the explosion of knowledge on the
      pathogenesis of enteric diseases experienced during the past decade, the number
      of diarrhoeal episodes and human deaths reported worldwide remains of apocalyptic
      dimensions. However, our better understanding of the pathogenic mechanisms
      involved in the onset of diarrhoea is finally leading to preventive
      interventions, such as the development of enteric vaccines, that may have a
      significant impact on the magnitude of this human plague. The application of a
      multidisciplinary approach to study bacterial pathogenesis, along with the recent
      sequencing of entire microbial genomes, have made possible discoveries that are
      changing the way scientists view the bacterium-host interaction. Today, research
      on the molecular basis of the pathogenesis of infective diarrhoeal diseases of
      necessity transcends established boundaries between microbiology, cell biology,
      intestinal pathophysiology, and immunology. This review focuses on the most
      recent outcomes of this multidisciplinary effort.

PMID- 11953327
TI  - Novel targets for the control of secretory diarrhoea.
AB  - Secretory diarrhoea continues to be a major clinical problem worldwide. It is now
      recognised that the enteric nervous system plays an important role in the
      pathogenesis of enterotoxin mediated intestinal secretion, which has resulted in
      the identification of novel therapeutic targets for the treatment of acute watery
      diarrhoea.

PMID- 11953328
TI  - Helicobacter and gastric MALT lymphoma.
AB  - Helicobacter pylori infection is a pre-MALT lymphoma condition. H pylori
      eradication leads to complete remission in 80% of low grade stage E1 lymphomas,
      with a yearly recurrence rate of approximately 5%. The possibility for complete
      remission in high grade lymphomas needs to be investigated in prospective
      studies. In addition, the significance of persistent B cell monoclonality (stable
      disease? danger of relapse? regression of monoclonality?) needs to be
      investigated in follow up studies.

PMID- 11953329
TI  - Cyclooxygenase inhibition: between the devil and the deep blue sea.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) account for more reports of drug
      related toxicity than any other class of drugs. Their most widely recognised
      adverse effects are on the gastrointestinal tract. They cause acute erosions and
      chronic ulcers that result in hospitalisation and death because of ulcer bleeding
      and perforation. Between them, aspirin and non-aspirin NSAIDs may account for
      more than half of all episodes of ulcer bleeding and perforation.

PMID- 11953330
TI  - The genetic jigsaw of inflammatory bowel disease.
AB  - Following a prolonged period of relative inertia, real progress has been made in
      the past few years in understanding the pathogenesis of the chronic inflammatory
      bowel diseases, Crohn's disease and ulcerative colitis. Clinical experience,
      epidemiological studies, and molecular genetics have provided strong evidence
      that both genetic and environmental factors are important in disease
      pathogenesis, and gene-environmental interaction determines disease
      susceptibility and behaviour.

PMID- 11953331
TI  - Influence of treatment on morphological features of mucosal inflammation.
AB  - Microscopic analysis of endoscopically obtained tissue samples is important for
      the diagnosis of several gastrointestinal disorders such as gastritis and chronic
      inflammatory bowel disease (IBD). Histologically disease activity is based on the
      presence of neutrophilic polymorphonuclear leucocytes in conjunction with
      epithelial damage. Effective eradication treatment for Helicobacter pylori
      related gastritis reduces active inflammation rapidly whereas chronic
      inflammation decreases only slowly. Similar findings have been obtained for IBD.
      A literature review of clinical drug trials in IBD and the effect of various
      drugs on the microscopic features of Crohn's disease and immunohistochemistry for
      different markers was performed. Diagnostic microscopic features and the features
      characteristic for disease activity vary with time and treatment. The more
      recently developed drugs used for Crohn's disease can induce mucosal healing.

PMID- 11953332
TI  - New steroids and new salicylates in inflammatory bowel disease: a critical
      appraisal.
AB  - Although new salicylates are now available for the treatment of ulcerative
      colitis, sulphasazaline still has an important therapeutic role. The role of
      salicylates in Crohn's disease is limited to the mild activity phase; further
      data are required to clarify its role in maintenance on remission. New steroids
      are a real alternative to traditional steroids in active ulcerative colitis and
      Crohn's disease.

PMID- 11953334
TI  - Probiotics: a role in the treatment of intestinal infection and inflammation?
AB  - Probiotic therapy is based on the concept of normal healthy microflora. The
      development of novel means of characterising the gut microflora, in particular
      those based on the different levels of conservation in the ribosomal RNA
      sequences of different genera, have opened up new angles on the role of the gut
      microflora in health and disease. Components of the human intestinal microflora
      or organisms entering the intestine may have harmful or beneficial effects on
      human health. Abundant evidence implies that specific strains selected from the
      healthy gut microflora exhibit powerful antipathogenic and anti-inflammatory
      capabilities, and are consequently involved with enhanced colonisation resistance
      in the intestine. Realisation of this has led to the introduction of novel modes
      of therapeutic and prophylactic intervention based on the consumption of mono and
      mixed cultures of beneficial live microorganisms as probiotics.

PMID- 11953333
TI  - Small therapeutic molecules for the treatment of inflammatory bowel disease.
AB  - New therapies for inflammatory bowel disease are needed, because standard
      therapies fail to induce remission in about 30% of patients, and because of the
      relative inefficacy of current maintenance therapies. This review summarises the
      current status of the development of small therapeutic molecules for inflammatory
      bowel disease.

PMID- 11953336
TI  - pH-Hp: implications for dyspepsia management.

PMID- 11953335
TI  - Immunoregulation in the gut: success and failures in human disease.
AB  - In normal conditions, human gut mucosa is infiltrated with a large number of
      mononuclear cells. This is a reflection of the fact that human intestine is
      continuously subjected to a massive stimulation by luminal antigens. This state
      of "physiological" inflammation is a tightly controlled phenomenon, as several
      mucosal cells interact to generate and maintain an appropriate local immune
      response. Changes in cell type number and/or function, including the release of
      soluble mediators, have been associated with the development of chronic
      inflammatory diseases, such as Crohn's disease (CD) and ulcerative colitis (UC),
      the two major forms of inflammatory bowel disease. Evidence also indicates that
      the type of inflammatory response occurring in the intestine of patients with CD
      differs from that in UC, and this probably reflects distinct pathways of immune
      activation. In CD mucosa, a Th1 response with high IL-12 and IFNgamma production
      prevails, while in UC a humoral immunity appears to be predominant. Despite this,
      CD and UC share downstream inflammatory events, characterised by high levels of
      inflammatory cytokines, free radicals, matrix-degrading enzymes and growth
      factors.

PMID- 11953337
TI  - Natural history of dyspepsia.
AB  - Many individuals in the Western world suffer from heartburn, acid regurgitation,
      abdominal pain, or bowel habit disturbances. The reported prevalence of dyspepsia
      is approximately 25% with similar values for gastro-oesophageal reflux disease.
      While prevalence rates are stable over time, substantial changes occur in the
      main symptom profiles of sufferers. The economic costs of dyspepsia are
      considerable.

PMID- 11953338
TI  - Clinical and economic consequences of dyspepsia in the community.
AB  - Dyspepsia is a common problem where many sufferers do not seek healthcare. The
      clinical impact of the condition in the community and the economic costs were
      assessed using data from a large cross sectional survey. Dyspepsia may be costing
      society 1 billion pounds each year in the UK. Thus dyspepsia is a huge clinical
      and economic burden and cost effective management strategies and treatments are
      urgently required.

PMID- 11953339
TI  - Role of endoscopy and biopsy in the work up of dyspepsia.
AB  - Endoscopy is recommended as the first investigation in the work up of a patient
      with dyspeptic symptoms and is essential in the classification of the patient's
      condition as organic or functional dyspepsia. Although the correlation between
      mucosal alterations and symptom pattern is difficult, endoscopy will remain the
      initial investigation of choice for clinically relevant abnormalities that need
      proper detection and biopsy.

PMID- 11953340
TI  - Definitions of reflux disease and its separation from dyspepsia.
AB  - Management strategies for reflux disease are very different from those for
      dyspepsia and so differentiating between patients with "true" dyspepsia and those
      whose primary symptom is heartburn is a key step in their management. This
      separation has become more clear during the last decade as insights into reflux
      disease and dyspepsia have improved. It is likely that the use of short self
      administered questionnaires in routine clinical care will improve the reliability
      of separation of reflux induced symptoms from true dyspepsia.

PMID- 11953342
TI  - Assessment of outcome in dyspepsia: has progress been made?
AB  - There is a lack of consensus among researchers on how to best measure outcome in
      functional dyspepsia trials and more importantly a lack of validated outcome
      measures. If symptoms resolve completely, treatment has been successful but with
      partial improvement interpretation is less straightforward. It is most likely
      that these issues will only be resolved if unequivocally efficacious treatments
      emerge to which the different outcome measures can be compared. Recently, a few
      validated outcome measures have been developed which look promising.

PMID- 11953343
TI  - Combined analysis of the ORCHID and OCAY studies: does eradication of
      Helicobacter pylori lead to sustained improvement in functional dyspepsia
      symptoms?
AB  - Currently, one of the most important unresolved questions concerning Helicobacter
      pylori is whether eradication of the organism leads to a sustained improvement in
      symptoms in patients diagnosed with functional (non-ulcer) dyspepsia. Recently,
      two very similar studies, the ORCHID and OCAY studies, have been completed and
      the combined results of these two multicentre, multinational, randomised, double
      blind, controlled clinical trials are reviewed.

PMID- 11953346
TI  - The potential role of acid suppression in functional dyspepsia: the BOND, OPERA,
      PILOT, and ENCORE studies.
AB  - Dyspepsia is a common condition in the general population but data are lacking on
      the benefits of effective acid inhibition with proton pump inhibitors in
      functional dyspepsia. The results of the large, randomised, double blind clinical
      trials, BOND and OPERA, the Scandinavian PILOT study, and a follow up study,
      ENCORE, are reviewed. BOND, OPERA, and PILOT aimed to address the question of
      whether effective acid inhibition with the proton pump inhibitor omeprazole
      relieves symptoms in patients with functional dyspepsia. ENCORE followed on from
      this, addressing the consequences of relieving symptoms in patients with
      functional dyspepsia once they are off therapy.

PMID- 11953345
TI  - Helicobacter pylori and functional dyspepsia: review of previous studies and
      commentary on new data.
AB  - Many studies have attempted to prove a link between Helicobacter pylori infection
      and functional dyspepsia but the results have been conflicting. Several
      mechanisms have been postulated for how H pylori associated inflammation disturbs
      antral and duodenal function but no pathophysiological explanation of how H
      pylori may cause dyspeptic symptoms is presently available.

PMID- 11953347
TI  - Approaches to uninvestigated dyspepsia.
AB  - Uninvestigated dyspepsia refers to patients with new or recurrent dyspeptic
      symptoms in whom no investigations have previously been undertaken. These
      patients are much more likely to present in primary than in secondary care. It is
      particularly important to be able to offer effective symptom relief to support
      the explanation, reassurance, and advice provided to patients, and low dose or
      standard dose proton pump inhibitor therapy appears to offer the most effective
      approach to empirical therapy of this kind.

PMID- 11953348
TI  - Helicobacter pylori test and treat strategy for young dyspeptic patients: new
      data.
AB  - Decision analysis models have given different conclusions on the value of the
      Helicobacter pylori "test and treat" strategy for the management of dyspepsia.
      This uncertainty relates to the lack of primary data on this strategy. Four
      randomised controlled trials have compared the H pylori "test and treat" strategy
      with prompt endoscopy and have allowed a more accurate decision analysis model to
      be constructed. The model indicates that the H pylori test and treat strategy is
      more cost effective than prompt endoscopy, and should be the new "gold standard"
      against which other strategies are compared.

PMID- 11953349
TI  - Management of uninvestigated dyspepsia: review and commentary.
AB  - Up to 40% of individuals complain of dyspepsia but only 25% of these present to
      their general practitioner. If symptoms have been present for a relatively short
      period the majority can be managed by reassurance and symptomatic treatment.
      Those with a longer history require empirical treatment with more powerful
      medication, endoscopy, testing for Helicobacter pylori, or a combination of these
      approaches. There is some debate about whether the treatment of Helicobacter
      pylori infection is an appropriate strategy for patients with dyspepsia. It is
      the general practitioner who determines how the uninvestigated patient with
      dyspepsia will be managed because those referred to hospital usually undergo
      endoscopy at an early stage.

PMID- 11953351
TI  - H(2) receptor antagonists and prokinetics in dyspepsia: a critical review.
AB  - Drug treatment of patients with functional dyspepsia is controversial but H(2)
      receptor antagonists have been the mainstay of treatment. For patients with
      symptoms suggestive of dysmotility, prokinetics such as cisapride have been used.
      A large number of clinical trials have been unable to produce definite answers as
      to whether any of these treatment modalities are truly efficacious. This is
      partly due to the fact that the methodology and reporting of the majority of
      trials evaluating the symptomatic effects of H(2) receptor antagonists and
      cisapride are severely flawed. Based on the current literature, H(2) receptor
      antagonists may possibly have a therapeutic gain of approximately 20% over
      placebo. Evaluating the therapeutic gain of cisapride is more difficult but meta
      analyses indicate a somewhat larger effect.

PMID- 11953352
TI  - Use of antisecretory agents as a trial of therapy.
AB  - Dyspepsia is a common clinical condition, and its diagnostic evaluation and
      treatment result in the expenditure of enormous healthcare resources each year.
      Studies indicate that the omeprazole test is the most sensitive and cost
      effective test for diagnosing gastro-oesophageal reflux disease (GORD) in
      patients with extra-oesophageal or more "classic" symptoms suggestive of GORD.
      Studies also indicate that a therapeutic trial of omeprazole in patients with
      dyspepsia results in greater symptom improvement and lower costs than treatment
      with less potent acid suppression.

PMID- 11953353
TI  - Management of reflux disease.
AB  - The management of reflux disease can be divided into three major phases, the
      first being diagnosis and severity assessment, the second, prompt initial control
      of symptoms, and the third, selection of a long term management approach that is
      tailored to meet individual patient needs and preferences. Throughout these
      phases of management, the major priorities should include achieving patient
      satisfaction and minimising management costs.

PMID- 11953354
TI  - Dyspepsia: management guidelines for the millennium.
AB  - The annual prevalence of dyspepsia in Western countries is approximately 25%, and
      the condition accounts for 2-5% of all primary care consultations, yet optimal
      management remains a subject of considerable debate. Some of the outstanding
      issues and considerations in the management of dyspepsia are discussed, providing
      an overview of current thinking and recommendations on patient management by
      primary care physicians and specialists.

PMID- 11953356
TI  - Salmonella enterica serotype Typhimurium and its host-adapted variants.

PMID- 11953357
TI  - Transient requirement of the PrrA-PrrB two-component system for early
      intracellular multiplication of Mycobacterium tuberculosis.
AB  - Adaptive regulation of gene expression in response to environmental changes is a
      general property of bacterial pathogens. By screening an ordered transposon
      mutagenesis library of Mycobacterium tuberculosis, we have identified three
      mutants containing a transposon in the coding sequence or in the 5' regions of
      genes coding for two-component signal transduction systems (trcS, regX3, prrA).
      The intracellular multiplication capacity of the three mutants was investigated
      in mouse bone marrow-derived macrophages. Only the prrA mutant showed a defect in
      intracellular growth during the early phase of infection, and this defect was
      fully reverted when the mutant was complemented with prrA-prrB wild-type copies.
      The mutant phenotype was transient, as after 1 week this strain recovered full
      growth capacity to reach levels similar to that of the wild type at day 9.
      Moreover, a transient induction of prrA promoter activity was observed during the
      initial phase of macrophage infection, as shown by a prrA promoter-gfp fusion in
      M. bovis BCG infecting the mouse macrophages. The concordant transience of the
      prrA mutant phenotype and prrA promoter activity indicates that the PrrA-PrrB two
      component system is involved in the environmental adaptation of M. tuberculosis,
      specifically in an early phase of the intracellular growth, and that, similar to
      other facultative intracellular parasites, M. tuberculosis can use genes
      temporarily required at different stages in the course of macrophage infection.

PMID- 11953358
TI  - Functional substitution of the TibC protein of enterotoxigenic Escherichia coli
      strains for the autotransporter adhesin heptosyltransferase of the AIDA system.
AB  - The plasmid-encoded AIDA (adhesin involved in diffuse adherence) autotransporter
      protein derived from diffuse-adhering clinical Escherichia coli isolate 2787 and
      the TibA (enterotoxigenic invasion locus B) protein encoded by the chromosomal
      tib locus of enterotoxigenic E. coli (ETEC) strain H10407 are posttranslationally
      modified by carbohydrate substituents. Analysis of the AIDA-I adhesin showed that
      the modification involved heptose residues. AIDA-I is modified by the
      heptosyltransferase activity of the product of the aah gene, which is located
      directly upstream of adhesin-encoding gene aidA. The carbohydrate modification of
      the TibA adhesin/invasin is mediated by the TibC protein but has not been
      elucidated. Based on the sequence similarities between TibC and AAH
      (autotransporter adhesin heptosyltransferase) and between the TibA and the AIDA
      proteins we hypothesized that the AIDA system and the Tib system encoded by the
      tib locus are structurally and functionally related. Here we show that (i) TibC
      proteins derived from different ETEC strains appear to be highly conserved, (ii)
      recombinant TibC proteins can substitute for the AAH heptosyltransferase in
      introducing the heptosyl modification to AIDA-I, (iii) this modification is
      functional in restoring the adhesive function of AIDA-I, (iv) a single amino acid
      substitution at position 358 completely abolishes this activity, and (v)
      antibodies directed at the functionally active AIDA-I recognize a protein
      resembling modified TibA in ETEC strains. In summary, we conclude that, like AAH,
      TibC represents an example of a novel class of heptosyltransferases specifically
      transferring heptose residues onto multiple sites of a protein backbone. A
      potential consensus sequence for the modification site is suggested.

PMID- 11953359
TI  - A gene from the locus of enterocyte effacement that is required for
      enteropathogenic Escherichia coli to increase tight-junction permeability encodes
      a chaperone for EspF.
AB  - Disruption of the barrier properties of the enterocyte tight junction is believed
      to be important in the pathogenesis of diarrhea caused by enteropathogenic
      Escherichia coli (EPEC). This phenotype can be measured in vitro as the ability
      of EPEC to reduce transepithelial resistance (TER) across enterocyte monolayers
      and requires the products of the locus of enterocyte effacement (LEE) and, in
      particular, the type III secreted effector protein EspF. We report a second LEE
      encoded gene that is also necessary for EPEC to fully reduce TER. rorf10 is not
      necessary for EPEC adherence, EspADB secretion, or formation of attaching and
      effacing lesions. However, rorf10 mutants have a diminished TER phenotype,
      reduced intracellular levels of EspF, and a reduced ability to translocate EspF
      into epithelial cells. The product of rorf10 is a 14-kDa intracellular protein
      rich in alpha-helices that specifically interacts with EspF but not with Tir or
      other EPEC secreted proteins. These properties are consistent with the hypothesis
      that rorf10 encodes a type III secretion chaperone for EspF, and we rename this
      protein CesF, the chaperone for EPEC secreted protein F.

PMID- 11953360
TI  - Protection against bacterial superantigen staphylococcal enterotoxin B by passive
      vaccination.
AB  - We investigated the ability of two overlapping fragments of staphylococcal
      enterotoxin B (SEB), which encompass the whole toxin, to induce protection and
      also examined if passive transfer of chicken anti-SEB antibodies raised against
      the holotoxin could protect rhesus monkeys against aerosolized SEB. Although both
      fragments of SEB were highly immunogenic, the fragments failed to protect mice
      whether they were injected separately or injected together. Passive transfer of
      antibody generated in chickens (immunoglobulin Y [IgY]) against the whole toxin
      suppressed cytokine responses and was protective in mice. All rhesus monkeys
      treated with the IgY specific for SEB up to 4 h after challenge survived lethal
      SEB aerosol exposure. These findings suggest that large fragments of SEB may not
      be ideal for productive vaccination, but passive transfer of SEB-specific
      antibodies protects nonhuman primates against lethal aerosol challenge. Thus,
      antibodies raised in chickens against the holotoxin may have potential
      therapeutic value within a therapeutic window of opportunity after SEB encounter.

PMID- 11953361
TI  - Mucosal tolerance to a bacterial superantigen indicates a novel pathway to
      prevent toxic shock.
AB  - Enterotoxins with superantigenic properties secreted during systemic
      Staphylococcus aureus infection are responsible for toxic shock. We show that
      intranasal administration of staphylococcal enterotoxin A (SEA), but not a
      recombinant SEA lacking superantigenic activity, protected mice against lethal
      systemic SEA challenge. Protection was superantigen specific since intranasal
      exposure to SEA would not protect against death caused by subsequent toxic shock
      syndrome toxin 1 systemic challenge. Protection was neither due to selective
      depletion of SEA-specific T-cell receptor Vbeta families nor due to production of
      neutralizing anti-SEA antibodies. Importantly, the production of interleukin 10
      (IL-10) induced by "tolerization" (that is, by the induction of immunological
      tolerance) contributed to the observed protection against lethal superantigen
      triggered disease. In support of this notion we found that (i) significantly
      increased levels of IL-10 in sera of "tolerized" animals (that is, animals
      rendered tolerant) and (ii) IL-10(-/-) mice could not be tolerized by mucosal SEA
      administration. Altogether, this is the first study to show that mucosal
      tolerance to a superantigen is readily triggered by means of immunodeviation.

PMID- 11953362
TI  - Gender is a major determinant of the clinical evolution and immune response in
      hamsters infected with Leishmania spp.
AB  - In regions where leishmaniasis is endemic, clinical disease is usually reported
      more frequently among males than females. This difference could be due to
      disparate risks of exposure of males and females, but gender-related differences
      in the host response to infection may also play a role. Experimental studies of
      the influence of gender on Leishmania infection have not included parasites of
      the subgenus Viannia, which is the most common cause of cutaneous leishmaniasis
      in the Americas. Mice are not readily susceptible to infection by Leishmania
      (Viannia) spp., but cutaneous infection of hamsters with L. (V.) panamensis or L.
      (V.) guyanensis resulted in chronic lesions typical of the human disease caused
      by these parasites. Strikingly, infection of male hamsters resulted in
      significantly greater lesion size and severity, an increased rate of
      dissemination to distant cutaneous sites, and a greater parasite burden in the
      draining lymph node than infection in female animals. Two lines of evidence
      indicated this gender-related difference in disease evolution was determined at
      least in part by the sex hormone status of the animal. First, prepubertal male
      animals had smaller and/or less severe cutaneous lesions than adult male animals.
      Second, infection of testosterone-treated female animals resulted in
      significantly larger lesions than in untreated female animals. The increased
      severity of disease in male compared to female animals was associated with
      significantly greater intralesional expression of interleukin-4 (IL-4) (P =
      0.04), IL-10 (P = 0.04), and transforming growth factor beta (TGF-beta) (P <
      0.001), cytokines known to promote disease in experimental leishmaniasis. There
      was a direct correlation between the expression of TGF-beta mRNA and lesion size
      (Spearman's correlation coefficient = 0.873; P < 0.001). These findings
      demonstrate an inherent risk of increased disease severity in male animals, which
      is associated with a more permissive immune response.

PMID- 11953363
TI  - DsbA and DsbC are required for secretion of pertussis toxin by Bordetella
      pertussis.
AB  - The Dsb family of enzymes catalyzes disulfide bond formation in the gram-negative
      periplasm, which is required for folding and assembly of many secreted proteins.
      Pertussis toxin is arguably the most complex toxin known: it is assembled from
      six subunits encoded by five genes (for subunits S1 to S5), with 11
      intramolecular disulfide bonds. To examine the role of the Dsb enzymes in
      assembly and secretion of pertussis toxin, we identified and mutated the
      Bordetella pertussis dsbA, dsbB, and dsbC homologues. Mutations in dsbA or dsbB
      resulted in decreased levels of S1 (the A subunit) and S2 (a B-subunit protein),
      demonstrating that DsbA and DsbB are required for toxin assembly. Mutations in
      dsbC did not impair assembly of periplasmic toxin but resulted in decreased toxin
      secretion, suggesting a defect in the formation of the Ptl secretion complex.

PMID- 11953364
TI  - Enterohemorrhagic Escherichia coli infection induces interleukin-8 production via
      activation of mitogen-activated protein kinases and the transcription factors NF
      kappaB and AP-1 in T84 cells.
AB  - Enterohemorrhagic Escherichia coli (EHEC) infections are associated with
      hemorrhagic colitis and the hemolytic-uremic syndrome (HUS). In vivo, elevated
      plasma levels of the proinflammatory cytokine interleukin-8 (IL-8) in EHEC
      infected children are correlated with a high risk of developing HUS. As IL-8 gene
      transcription is regulated by the transcription factors NF-kappaB and AP-1, we
      analyzed the role of these factors in the regulation of IL-8 production after
      infection of the epithelial intestinal T84 cell line by EHEC. By 6 h of
      infection, EHEC had induced significant secretion of IL-8 (35.84 +/- 6.76 ng/ml
      versus 0.44 +/- 0.04 ng/ml in control cells). EHEC induced AP-1 and NF-kappaB
      activation by 3 h of infection. Moreover, the three mitogen-activated protein
      kinases (MAPK) (ERK1/2, p38, and JNK) were phosphorylated in EHEC-infected T84
      cells concomitant with induction of AP-1 DNA binding activity, and IkappaB-alpha
      was phosphorylated and then degraded concomitant with induction of NF-kappaB DNA
      binding activity. Pretreatment of cells with the highly specific MEK1/2 inhibitor
      U0126, the p38 inhibitor SB203580, and/or the proteasome inhibitor ALLN led to
      inhibition of the IL-8 secretion induced in EHEC-infected T84 cells. These
      findings demonstrate that (i) EHEC can induce in vitro a potent proinflammatory
      response by secretion of IL-8 and (ii) the secretion of IL-8 is due to the
      involvement of MAPK, AP-1, and NF-kappaB signaling pathways.

PMID- 11953365
TI  - Global analysis of outer membrane proteins from Leptospira interrogans serovar
      Lai.
AB  - Recombinant leptospiral outer membrane proteins (OMPs) can elicit immunity to
      leptospirosis in a hamster infection model. Previously characterized OMPs appear
      highly conserved, and thus their potential to stimulate heterologous immunity is
      of critical importance. In this study we undertook a global analysis of
      leptospiral OMPs, which were obtained by Triton X-114 extraction and phase
      partitioning. Outer membrane fractions were isolated from Leptospira interrogans
      serovar Lai grown at 20, 30, and 37 degrees C with or without 10% fetal calf
      serum and, finally, in iron-depleted medium. The OMPs were separated by two
      dimensional gel electrophoresis. Gel patterns from each of the five conditions
      were compared via image analysis, and 37 gel-purified proteins were tryptically
      digested and characterized by mass spectrometry (MS). Matrix-assisted laser
      desorption ionization-time-of-flight MS was used to rapidly identify leptospiral
      OMPs present in sequence databases. Proteins identified by this approach included
      the outer membrane lipoproteins LipL32, LipL36, LipL41, and LipL48. No known
      proteins from any cellular location other than the outer membrane were
      identified. Tandem electrospray MS was used to obtain peptide sequence
      information from eight novel proteins designated pL18, pL21, pL22, pL24, pL45,
      pL47/49, pL50, and pL55. The expression of LipL36 and pL50 was not apparent at
      temperatures above 30 degrees C or under iron-depleted conditions. The expression
      of pL24 was also downregulated after iron depletion. The leptospiral major OMP
      LipL32 was observed to undergo substantial cleavage under all conditions except
      iron depletion. Additionally, significant downregulation of these mass forms was
      observed under iron limitation at 30 degrees C, but not at 30 degrees C alone,
      suggesting that LipL32 processing is dependent on iron-regulated extracellular
      proteases. However, separate cleavage products responded differently to changes
      in growth temperature and medium constituents, indicating that more than one
      process may be involved in LipL32 processing. Furthermore, under iron-depleted
      conditions there was no concomitant increase in the levels of the intact form of
      LipL32. The temperature- and iron-regulated expression of LipL36 and the iron
      dependent cleavage of LipL32 were confirmed by immunoblotting with specific
      antisera. Global analysis of the cellular location and expression of leptospiral
      proteins will be useful in the annotation of genomic sequence data and in
      providing insight into the biology of Leptospira.

PMID- 11953366
TI  - Nonviable Burkholderia mallei induces a mixed Th1- and Th2-like cytokine response
      in BALB/c mice.
AB  - Nonviable cell preparations of Burkholderia mallei, the causative agent of
      glanders, were evaluated as potential vaccine candidates in a BALB/c murine
      model. Three different B. mallei cell preparations plus Alhydrogel were
      evaluated: a heat-killed preparation, an irradiation-inactivated preparation, and
      a preparation of a capsule-negative mutant strain which had been irradiation
      inactivated. BALB/c mice were vaccinated twice with the different B. mallei
      preparations, and spleens and sera were collected to determine their cellular and
      humoral immune responses. All three bacterial cell preparations had essentially
      the same results in two cellular immune response assays. In a splenocyte
      proliferation assay, the amount of cell proliferation in response to the
      homologous immunogen, concanavalin A, or lipopolysaccharide was similar for all
      the cell preparations. Also, splenocytes from the inoculated mice expressed
      interleukin 2 (IL-2), gamma interferon, and small amounts of IL-4 and IL-5, and
      more IL-10 cytokine in the presence of the homologous antigen. When the
      immunoglobulin subclasses from these mice were examined, they all produced higher
      levels of IgG1 than IgG2a subclasses. The higher ratio of IgG1 to IgG2a was not
      due to the amount of the immunogen or the adjuvant (Alhydrogel) used in the
      BALB/c mice. The cell preparations did not protect the vaccinated mice from a
      live challenge (>300 50% lethal doses). Our results suggest that in BALB/c mice,
      a mixed T-helper-cell-like response to nonviable B. mallei is obtained, as
      demonstrated by a Th1- and Th2-like cytokine response and a Th2-like subclass
      immunoglobulin response. This may be the reason for the inability of the B.
      mallei cells that were examined as candidate vaccines to protect the mice from a
      live challenge.

PMID- 11953367
TI  - Novel Aeromonas hydrophila PPD134/91 genes involved in O-antigen and capsule
      biosynthesis.
AB  - The sequences of the O-antigen and capsule gene clusters of the virulent
      Aeromonas hydrophila strain PPD134/91 were determined. The O-antigen gene cluster
      is 17,296 bp long and comprises 17 genes. Seven pathway genes for the synthesis
      of rhamnose and mannose, six transferase genes, one O unit flippase gene, and one
      O-antigen chain length determinant gene were identified by amino acid sequence
      similarity. PCR and Southern blot analysis were performed to survey the
      distribution of these 17 genes among 11 A. hydrophila strains of different
      serotypes. A. hydrophila PPD134/91 might belong to serotype O:18, as represented
      by JCM3980; it contained all the same O-antigen genes as JCM3980 (97 to 100%
      similarity at the DNA and amino acid levels). The capsule gene cluster of A.
      hydrophila PPD134/91 is 17,562 bp long and includes 13 genes, which were
      assembled into three distinct regions similar to those of the group II capsule
      gene cluster of Escherichia coli and other bacteria. Regions I and III contained
      four and two capsule transport genes, respectively. Region II had five genes
      which were highly similar to capsule synthesis pathway genes found in other
      bacteria. Both the purified O-antigen and capsular polysaccharides increased the
      ability of the avirulent A. hydrophila strain PPD35/85 to survive in naive
      tilapia serum. However, the purified surface polysaccharides had no inhibitory
      effect on the adhesion of A. hydrophila PPD134/91 to carp epithelial cells.

PMID- 11953368
TI  - Evaluation of receptor binding specificity of Escherichia coli K88 (F4) fimbrial
      adhesin variants using porcine serum transferrin and glycosphingolipids as model
      receptors.
AB  - Diarrheal disease caused by enterotoxigenic Escherichia coli expressing the K88
      (F4) fimbrial adhesin (K88 ETEC) is a significant source of mortality and
      morbidity among newborn and weaned piglets. K88 fimbrial adhesins are filamentous
      surface appendages whose lectin (carbohydrate-binding) activity allows K88 ETEC
      to attach to specific glycoconjugates (receptors) on porcine intestinal
      epithelial cells. There are three variants of K88 adhesin (K88ab, K88ac, and
      K88ad), which possess different, yet related, carbohydrate-binding specificities.
      We used porcine serum transferrin (pSTf) and purified glycosphingolipids (GSL) to
      begin to define the minimal recognition sequence for K88 adhesin variants. We
      found that K88ab adhesin binds with high affinity to pSTf (dissociation constant,
      75 microM), while neither K88ac nor K88ad adhesin recognizes pSTf. Degradation of
      the N-glycan on pSTf by extensive metaperiodate treatment abolished its
      interaction with the K88ab adhesin, indicating that the K88ab adhesin binds to
      the single N-glycan found on pSTf. Using exoglycosidase digestion of the pSTf
      glycan, we demonstrated that K88ab adhesin recognizes N-acetylglucosamine
      (GlcNAc) residues in the core of the N-glycan on pSTf. All three K88 variants
      were found to bind preferentially to GSL containing a beta-linked N
      acetylhexosamine (HexNAc), either GlcNAc or N-acetylgalactosamine, in the
      terminal position or, alternatively, in the penultimate position with galactose
      in the terminal position. Considering the results from pSTf and GSL binding
      studies together, we propose that the minimal recognition sequence for the K88
      adhesin variants contains a beta-linked HexNAc. In addition, the presence of a
      terminal galactose beta-linked to this HexNAc residue enhances K88 adhesin
      binding.

PMID- 11953369
TI  - Receptor-based antidote for diphtheria.
AB  - Although equine diphtheria antitoxin may be an effective therapy for human
      diphtheria, its use often induces serum sickness. We describe here a strategy for
      developing an alternative treatment based on the human diphtheria toxin (DT)
      receptor/heparin-binding epidermal growth factor-like growth factor (HB-EGF)
      precursor. Recombinant mature human HB-EGF acts as a soluble receptor analog,
      binding radioiodinated DT and preventing its binding to the cellular DT
      receptor/HB-EGF precursor. However, the possibility existed that radioiodinated
      DT-HB-EGF complexes associate with cells due to the binding of the heparin
      binding domain of recombinant HB-EGF to cell surface heparan sulfate
      proteoglycans. This possibility was confirmed by performing DT binding studies in
      the presence of heparin. A recombinant truncated HB-EGF (residues 106 to 149),
      which lacks most of the heparin-binding domain, showed an essentially heparin
      independent binding of radioiodinated DT to cells. Furthermore, it was a more
      effective inhibitor of DT binding than was recombinant mature HB-EGF. Since
      mature HB-EGF is a known ligand for the EGF receptor and is thus highly mitogenic
      (tumorigenic), we then changed amino acid residues in the EGF-like domain of the
      recombinant truncated HB-EGF and demonstrated that this DT receptor analog
      (I117A/L148A) displayed a low mitogenic effect. The truncated (I117A/L148A) HB
      EGF protein retained high DT binding affinity, as confirmed by using surface
      plasmon resonance. Our results suggest that the truncated (I117A/L148A) HB-EGF
      protein could be an effective, safe antidote for human diphtheria.

PMID- 11953370
TI  - Genome-based identification of chromosomal regions specific for Salmonella spp.
AB  - Acquisition of genomic elements by horizontal gene transfer represents an
      important mechanism in the evolution of bacterial species. Pathogenicity islands
      are a subset of horizontally acquired elements present in various pathogens.
      These elements are frequently located adjacent to tRNA genes. We performed a
      comparative genome analysis of Salmonella enterica serovars Typhi and Typhimurium
      and Escherichia coli and scanned tRNA loci for the presence of species-specific,
      horizontally acquired genomic elements. A large number of species-specific
      elements were identified. Here, we describe the characteristics of four large
      chromosomal insertions at tRNA genes of Salmonella spp. The tRNA-associated
      elements harbor various genes previously identified as single virulence genes,
      indicating that these genes have been acquired with large chromosomal insertions.
      Southern blot analyses confirmed that the tRNA-associated elements are specific
      to Salmonella and also indicated a heterogeneous distribution within the
      salmonellae. Systematic scanning for insertions at tRNA genes thus represents a
      tool for the identification of novel pathogenicity islands.

PMID- 11953371
TI  - Human gingival fibroblasts rescue butyric acid-induced T-cell apoptosis.
AB  - We previously demonstrated that butyric acid, an extracellular metabolite from
      periodontopathic bacteria, induces cytotoxicity and apoptosis in murine
      thymocytes, splenic T cells, and human Jurkat T cells. In this study, we used a
      cell-to-cell interaction system to examine the contribution of gingival
      fibroblasts to the regulation of T-cell death induced by butyric acid. Butyric
      acid slightly suppressed fibroblast viability in a concentration-dependent
      fashion. However, DNA fragmentation assays indicated that butyric acid did not
      induce apoptosis for up to 21 h in human gingival fibroblasts (Gin 1, F41-G, and
      H. pulp cells). The culture supernatants were assayed for interleukin 1alpha (IL
      1alpha), IL-1beta, IL-6, IL-8, IL-11, tumor necrosis factor alpha, and
      transforming growth factor beta, but only the IL-6, IL-8, and IL-11 levels were
      significantly increased by addition of butyric acid. Butyric acid- or Fas-induced
      Jurkat-cell apoptosis was attenuated when Jurkat cells were cocultured with
      either F41-G or Gin 1 cells that had been preincubated for 6 h with butyric acid.
      IL-8 slightly stimulated butyric acid- or Fas-induced Jurkat-cell apoptosis in a
      dose-dependent manner, although a low dose of IL-8 had a mildly inhibitory effect
      on apoptosis. In contrast, IL-6 and IL-11 significantly suppressed butyric acid-
      or Fas-induced apoptosis in a dose-dependent fashion. Furthermore, the addition
      of monoclonal antibodies against human IL-6 and IL-11 to cocultures of gingival
      fibroblasts and Jurkat cells partially eliminated T-cell recovery. These results
      suggest that the proinflammatory cytokines such as IL-6 and IL-11, produced in
      fibroblasts stimulated with butyric acid, are involved in the attenuation of T
      cell apoptosis by gingival fibroblasts.

PMID- 11953372
TI  - Dendritic cells as effector cells: gamma interferon activation of murine
      dendritic cells triggers oxygen-dependent inhibition of Toxoplasma gondii
      replication.
AB  - Toxoplasma gondii is an obligate intracellular parasite that infects a wide
      variety of nucleated cells in its numerous intermediate hosts, including humans.
      Much interest has focused on the ability of gamma interferon (IFN-gamma)
      activated macrophages to prevent intracellular replication, but some other cells
      (e.g., fibroblasts, endothelial cells, microglial cells, astrocytes, enterocytes
      and retinal pigment cells) can also be activated to induce this inhibition of
      proliferation. Dendritic cells are generally known to be involved in the
      induction of immune responses, but no previous study had investigated the
      possibility that dendritic cells may act as effector cells of this system. Our
      results show that IFN-gamma-activation inhibits the replication of T. gondii in
      dendritic cells, with the inhibition being dose dependent. Neither nitrogen
      derivatives nor tryptophan starvation appears to be involved in the inhibition of
      parasite replication by IFN-gamma. Experiments with oxygen scavengers indicate
      that intracellular T. gondii replication is oxygen dependent. Our findings
      suggest that, in addition to their essential role in stimulating the immune
      system, dendritic cells probably act as effector cells in the first line of
      defense against pathogen invasion.

PMID- 11953373
TI  - Protection of killer antiidiotypic antibodies against early invasive
      aspergillosis in a murine model of allogeneic T-cell-depleted bone marrow
      transplantation.
AB  - Antiidiotypic monoclonal antibodies (MAbs) representing the internal image of a
      yeast killer toxin (KT) have therapeutic potential against several fungal
      infections. The efficacy of KT MAbs against Aspergillus fumigatus was
      investigated in a mouse model of T-cell-depleted allogeneic bone marrow
      transplantation (BMT) with invasive pulmonary aspergillosis. Mice were highly
      susceptible to infection at 3 days post-BMT, when profound neutropenia was
      observed both in the periphery and in the lungs. Treatment with KT MAbs protected
      the mice from infection, as judged by the long-term survival and decreased
      pathology associated with inhibition of fungal growth and hyphal development in
      the lungs. In vitro, similar to polymorphonuclear neutrophils, KT MAbs
      significantly inhibited the hyphal development and metabolic activity of
      germinated Aspergillus conidia. These results indicate that mimicking the action
      of neutrophils could be a strategy through which KT MAbs exert therapeutic
      efficacy in A. fumigatus infections.

PMID- 11953375
TI  - Chlamydia pneumoniae infection induces differentiation of monocytes into
      macrophages.
AB  - Migration and differentiation of monocytes to the intima of blood vessels may be
      a crucial first step in the development of atherosclerosis associated with
      Chlamydia (Chlamydophila) pneumoniae. However, the involvement of C. pneumoniae
      infection in such steps is not clear. In the present study, therefore, the
      differentiation-inducing activity of C. pneumoniae to monocytes was examined.
      Human THP-1 monocytic cell line cells were infected with C. pneumoniae, and the
      differentiation of monocytes to macrophages was assessed by cell morphology,
      phagocytic activity, and expression of a cell surface adhesion molecule. The
      monocytic cells infected with viable bacteria markedly differentiated into
      macrophages associated with diffused cell morphology, increased uptake of
      polystyrene beads and increased ICAM-1 (intercellular adhesion molecule 1)
      expression on the cell surfaces. Heat-killed bacteria did not induce any
      morphological changes or increase of phagocytosis, but they did induce an
      increase of cell surface ICAM-1 expressions in THP-1 monocytic cells. The
      antibiotic minocycline treatment of infected cells resulted in marked inhibition
      of the cell differentiation as well as C. pneumoniae growth in the cells, but not
      ICAM-1 expression. In addition, the experiments with human peripheral blood
      monocytes infected with C. pneumoniae also showed the differentiation of
      macrophages assessed by morphological change and phagocytic activity. These
      results indicate that C. pneumoniae infection may directly induce the
      differentiation of monocytes to macrophages. However, antigenic stimulation of
      monocytes with bacteria may not be sufficient for a full macrophage
      differentiation.

PMID- 11953374
TI  - Identification and cloning of a cryptococcal deacetylase that produces protective
      immune responses.
AB  - Cell-mediated immunity plays a crucial role in host defenses against Cryptococcus
      (Filobasidiella) neoformans. Therefore, the identification of cryptococcal
      antigens capable of producing T-cell-mediated responses, such as delayed-type
      hypersensitivity (DTH) reactions, may be useful in the development of immune
      based strategies to control cryptococcosis. In order to characterize DTH
      producing antigens, culture supernatants from the unencapsulated Cap-67 strain
      were separated by anion-exchange chromatography. After further fractionation by
      preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a purified
      protein with an apparent molecular mass of 25 kDa was found to produce DTH, as
      evidenced by increased footpad swelling in mice immunized with culture
      supernatants, relative to unimmunized mice. The 20-amino-acid N-terminal sequence
      of the 25-kDa protein was used to search data of the C. neoformans Genome
      Project. Based on the genomic DNA sequence, a DNA probe was used to screen a
      lambda cDNA library prepared from strain B3501. Clones were isolated containing
      the full-length gene (d25), which showed homology with a number of polysaccharide
      deacetylases from fungi and bacteria. The recombinant d25 protein expressed in
      Escherichia coli was similar to the natural one in DTH-producing activity.
      Moreover, immunization with either the natural or the recombinant protein
      prolonged survival and decreased fungal burden in mice challenged with the highly
      virulent C. neoformans strain H99. In conclusion, we have described the first
      cryptococcal gene whose product, a 25-kDa extracellular polysaccharide
      deacetylase, has been shown to induce protective immunity responses.

PMID- 11953376
TI  - Conservation, surface exposure, and in vivo expression of the Frp family of iron
      regulated cell wall proteins in Staphylococcus aureus.
AB  - Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis identified two
      conserved, immunogenic Staphylococcus aureus cell wall proteins, of 40 and 87
      kDa, expressed under iron-restricted growth conditions in vitro and in vivo. N
      terminal sequencing and subsequent genome analysis showed that these proteins are
      encoded by adjacent monocistronic open reading frames designated frpA and frpB,
      respectively. Studies with an S. aureus fur mutant confirmed that expression of
      FrpA and FrpB is regulated by Fur but that there also appears to be differential
      expression of these proteins in different iron-restricted media in vitro. FrpA
      and FrpB share some amino acid sequence homology with each other and with a
      putative S. aureus membrane protein, FrpC. frpC is the first gene of a Fur
      regulated operon encoding four proteins of unknown function (FrpC, -D, -G, and 
      H) and the binding protein (FrpE) and permease (FrpF) of a putative iron
      transporter. Antisense mutagenesis and bioassays showed that FrpA and FrpB are
      not required for growth of S. aureus under iron-restricted conditions in vitro
      and do not appear to be involved in the transport of iron from siderophores or in
      binding of hemin. Further phenotypic analysis suggested that FrpA may be involved
      in adhesion of S. aureus to plastic in vitro. Binding of S. aureus to microtiter
      wells was found to be iron regulated, and iron-restricted S. aureus containing
      antisense frpA or frpAB but not frpB constructs showed reduced binding compared
      to vector construct controls.

PMID- 11953377
TI  - The group B streptococcal C5a peptidase is both a specific protease and an
      invasin.
AB  - The group B streptococcus (GBS) is a major cause of pneumonia, sepsis, and
      meningitis in neonates and a serious cause of mortality or morbidity in
      immunocompromised adults. Although these streptococci adhere efficiently and
      invade a variety of tissue-specific epithelial and endothelial cells, adhesins
      and invasins are still unknown. All serotypes of GBS studied to date express C5a
      peptidase (SCPB) on their surface. This investigation addresses the possibility
      that this relatively large surface protein has additional activities. Rabbit anti
      SCPB serum inhibited invasion of lung epithelial A549 cells by the serotype Ia
      strain O90R, suggesting that SCPB is an invasin. This was confirmed by inserting
      an in-frame 25-amino-acid deletion into the scpB gene. Invasion of HEp2 and A549
      human cell lines was significantly reduced by the mutation. Enzyme-linked
      immunosorbent assays were used to demonstrate that purified SCPB protein binds
      directly to HEp2 and A549 cells and also binds the extracellular matrix protein
      fibronectin. Binding was dose dependent and saturable. These results suggested
      that SCPB is one of several potential invasins essential for GBS colonization of
      damaged epithelium.

PMID- 11953378
TI  - Vaccination of pregnant dams with intimin(O157) protects suckling piglets from
      Escherichia coli O157:H7 infection.
AB  - Cattle are important reservoirs of enterohemorrhagic Escherichia coli (EHEC)
      O157:H7 that cause disease in humans. Both dairy and beef cattle are
      asymptomatically and sporadically infected with EHEC. Our long-term goal is to
      develop an effective vaccine to prevent cattle from becoming infected and
      transmitting EHEC O157:H7 to humans. We used passive immunization of neonatal
      piglets (as a surrogate model) to determine if antibodies against EHEC O157
      adhesin (intimin(O157)) inhibit EHEC colonization. Pregnant swine (dams) with
      serum anti-intimin titers of < or =100 were vaccinated twice with purified
      intimin(O157) or sham-vaccinated with sterile buffer. Intimin(O157)-specific
      antibody titers in colostrum and serum of dams were increased after parenteral
      vaccination with intimin(O157). Neonatal piglets were allowed to suckle
      vaccinated or sham-vaccinated dams for up to 8 h before they were inoculated with
      10(6) CFU of a Shiga toxin-negative (for humane reasons) strain of EHEC O157:H7.
      Piglets were necropsied at 2 to 10 days after inoculation, and intestinal samples
      were collected for determination of bacteriological counts and histopathological
      analysis. Piglets that ingested colostrum containing intimin(O157)-specific
      antibodies from vaccinated dams, but not those nursing sham-vaccinated dams, were
      protected from EHEC O157:H7 colonization and intestinal damage. These results
      establish intimin(O157) as a viable candidate for an EHEC O157:H7
      antitransmission vaccine.

PMID- 11953379
TI  - Comparative and genetic analyses of the putative Vibrio cholerae
      lipopolysaccharide core oligosaccharide biosynthesis (wav) gene cluster.
AB  - We identified five different putative wav gene cluster types, which are
      responsible for the synthesis of the core oligosaccharide (OS) region of Vibrio
      cholerae lipopolysaccharide. Preliminary evidence that the genes encoded by this
      cluster are involved in core OS biosynthesis came from analysis of the recently
      released O1 El Tor V. cholerae genome sequence and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis of O1 El Tor mutant strains defective
      in three genes (waaF, waaL, and wavB). Investigations of 38 different V. cholerae
      strains by Southern blotting, PCR, and sequencing analyses showed that the O1 El
      Tor wav gene cluster type is prevalent among clinical isolates of different
      serogroups associated with cholera and environmental O1 strains. In contrast, we
      found differences in the wav gene contents of 19 unrelated non-O1, non-O139
      environmental and human isolates not associated with cholera. These strains
      contained four new wav gene cluster types that differ from each other in distinct
      gene loci, providing evidence for horizontal transfer of wav genes and for
      limited structural diversity of the core OS among V. cholerae isolates. Our
      results show genetic diversity in the core OS biosynthesis gene cluster and
      predominance of the type 1 wav gene locus in strains associated with clinical
      cholera, suggesting that a specific core OS structure could contribute to V.
      cholerae virulence.

PMID- 11953380
TI  - rgf encodes a novel two-component signal transduction system of Streptococcus
      agalactiae.
AB  - The adhesion of gram-positive bacteria to extracellular matrix (ECM) proteins is
      regarded as an important determinant of pathogenicity. A comparison of the
      adhesion of Streptococcus agalactiae strain O90R to different ECM proteins showed
      that the most pronounced binding could be observed for immobilized fibrinogen. To
      investigate the genetic determinants of S. agalactiae fibrinogen binding, a
      pGhost9:ISS1 mutant library was screened for mutants displaying reduced
      agglutination of fibrinogen-coated latex beads. A putative two-component signal
      transduction system was identified and designated rgfBDAC. It comprises genes
      encoding a putative response regulator of 218 amino acids and a putative
      histidine kinase of 426 amino acids. Comparison of the deduced proteins with the
      GenBank database revealed a significant similarity to quorum-sensing systems of
      gram-positive pathogens. Transcription analysis of the rgf locus showed that the
      encoding genes are located on one transcript. To further characterize the
      influence of the putative histidine kinase encoded in the rgf locus on the
      adhesion of S. agalactiae to immobilized fibrinogen, a targeted mutant of rgfC
      was generated. In comparison to the wild-type strain this mutant demonstrated
      altered fibrinogen binding capacities depending on bacterial cell density.
      Transcription analysis of secreted and surface-localized S. agalactiae proteins
      in the wild type and the rgfC mutant strain revealed that mRNA levels of the C5a
      peptidase gene scpB were increased in the mutant strain while the transcription
      of the secreted CAMP factor gene cfb was unaffected by this mutation. Based on
      these results, we hypothesize that rgf regulates the expression of bacterial cell
      surface components.

PMID- 11953381
TI  - Evidence for the emergence of non-O1 and non-O139 Vibrio cholerae strains with
      pathogenic potential by exchange of O-antigen biosynthesis regions.
AB  - The novel epidemic strain Vibrio cholerae O139 Bengal originated from a seventh
      pandemic O1 El Tor strain by antigenic shift resulting from homologous
      recombination-mediated exchange of O-antigen biosynthesis (wb*) clusters.
      Conservation of the genetic organization of wb* regions seen in other serogroups
      raised the possibility of the existence of pathogenic non-O1 and non-O139 V.
      cholerae strains that emerged by similar events. To test this hypothesis, 300 V.
      cholerae isolates of non-O1 and non-O139 serogroups were screened for the
      presence of virulence genes and an epidemic genetic background by DNA dot
      blotting, IS1004 fingerprinting, and restriction fragment length polymorphism
      (RFLP) analysis. We found four non-O1 strains (serogroups O27, O37, O53, and O65)
      with an O1 genetic backbone suggesting exchange of wb* clusters. DNA sequence
      analysis of the O37 wb* region revealed that a novel approximately 23.4-kb gene
      cluster had replaced all but the approximately 4.2-kb right junction of the 22-kb
      O1 wbe region. In sharp contrast to the backbones, the virulence regions of the
      four strains were quite heterogeneous; the O53 and O65 strains had the El Tor
      vibrio pathogenicity island (VPI) cluster, the O37 strain had the classical VPI
      cluster, and the O27 strain had a novel VPI cluster. Two of the four strains
      carried CTXphi; the O27 strain possessed a CTXphi with a recently reported immune
      specificity (rstR-4** allele) and a novel ctxB allele, and the O37 strain had an
      El Tor CTXphi (rstR(ET) allele) and novel ctxAB alleles. Although the O53 and O65
      strains lacked the ctxAB genes, they carried a pre-CTXphi (i.e., rstR(cla)).
      Identification of non-O1 and non-O139 serogroups with pathogenic potential in
      epidemic genetic backgrounds means that attention should be paid to possible
      future epidemics caused by these serogroups and to the need for new, rapid
      vaccine development strategies.

PMID- 11953382
TI  - Lipooligosaccharide and polysaccharide capsule: virulence factors of Neisseria
      meningitidis that determine meningococcal interaction with human dendritic cells.
AB  - In this work we analyzed the roles of meningococcal lipooligosaccharide (LOS) and
      capsule expression in the interaction of Neisseria meningitidis with human
      dendritic cells (DC). Infection of DC with serogroup B wild-type meningococci
      induced a strong burst of the proinflammatory cytokines and chemokines tumor
      necrosis factor alpha, interleukin-6 (IL-6), and IL-8. In contrast, a serogroup B
      mutant strain lacking LOS expression barely led to cytokine induction,
      demonstrating that meningococcal LOS is the main mediator of the proinflammatory
      response in human DC. Sialylation of meningococcal LOS did not influence cytokine
      secretion by DC. However, we found the phagocytosis of N. meningitidis by human
      DC to be inhibited by LOS sialylation. In addition, the expression of the
      meningococcal serogroup A, B, and C capsules dramatically reduced DC adherence of
      N. meningitidis and phagocytosis to some extent. Hence, LOS sialylation and
      capsule expression are independent mechanisms protecting N. meningitidis from the
      phagocytic activity of human DC.

PMID- 11953383
TI  - Diversity of the metalloprotease toxin produced by enterotoxigenic Bacteroides
      fragilis.
AB  - Enterotoxigenic Bacteroides fragilis (ETBF) strains produce a 20-kDa zinc
      metalloprotease toxin (BFT) associated with diarrheal disease of animals, young
      children, and adults. BFT stimulates secretion in intestinal loops in vivo and
      modifies epithelial cell morphology in vitro. The B. fragilis toxin (bft) gene
      from ETBF strain 86-5443-2-2 (piglet; bft-2) revealed significant nucleotide and
      predicted amino acid differences when compared to the bft gene from ETBF strain
      VPI 13784 (lamb; bft-1). This study compares BFT-1 and BFT-2, respectively,
      produced by ETBF strains VPI 13784 and 86-5443-2-2 purified using the Van Tassell
      method (38) and a modified purification scheme described herein. Multiple
      differences in the protein toxins produced by these ETBF strains were identified.
      First, purified BFT-1 eluted from a high-resolution anion-exchange column (Mono
      Q) at 0.22 +/- 0.005 M NaC1 versus 0.18 +/- 0.001 M NaC1 for BFT-2 (P < 0.001).
      Second, BFT-1 and BFT-2 exhibited different electrophoretic mobilities on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and reverse-phase fast protein
      liquid chromatography. Third, each BFT reacted with greater specificity to
      homologous rather than heterologous antisera. Fourth, BFT-2 had modest, but
      consistently, greater biological activity than BFT-1 when tested on HT29/C1 cells
      (P < or = 0.01). Together, these data indicate that these ETBF strains produce
      two distinct isotypes of BFT, termed BFT-1 (VPI 13784 BFT) and BFT-2 (86-5443-2-2
      BFT) to recognize the order in which the proteins were purified and genetic
      sequences identified. The modified purification scheme described in this report
      yields about two to three times more purified BFT protein than previous protocols
      and is less time consuming.

PMID- 11953384
TI  - Antigenic diversity in Eimeria maxima and the influence of host genetics and
      immunization schedule on cross-protective immunity.
AB  - Eimeria spp. are a group of highly successful intracellular protozoan parasites
      that develop within enterocytes. Eimeria maxima from the chicken is characterized
      by high immunogenicity (a small priming infection gives complete immunity to
      subsequent homologous challenge) and naturally occurring antigenically variant
      populations that do not completely cross-protect. In this study we examined the
      expression of antigenic diversity in E. maxima, as manifested by cross-strain
      protection in a series of inbred chicken lines. The IAH line of Light Sussex
      chickens and all lines of inbred White Leghorns were susceptible to primary
      infections with either of two strains (H and W) of E. maxima and were protected
      completely against challenge with the homologous strain of parasite. The extent
      of cross-protection against the heterologous parasite strain varied from 0 to
      almost 100% depending on host genetics. Interestingly, in one inbred line of
      chickens (line 15I) the cross-protective phenotype was directional and intensely
      influenced by the infection history of the host. The basis for the observed
      variation in cross-protection is not known, but our results suggest that the
      major histocompatibility complex is not a major genetic component of the
      phenotype. These results are discussed in relation to the number of protective
      antigens presented by complex pathogens and the development of immunoprotective
      responses in hosts of different genetic backgrounds.

PMID- 11953386
TI  - Analysis of factors affecting surface expression and immunogenicity of
      recombinant proteins expressed by gram-positive commensal vectors.
AB  - Several key protein structural attributes were altered in an effort to optimize
      expression and immunogenicity of a foreign protein (M protein from Streptococcus
      pyogenes) exposed on the surface of Streptococcus gordonii commensal bacterial
      vectors: (i) a shorter N-terminal region, (ii) the addition of a 94-amino-acid
      spacer, and (iii) the addition of extra C-repeat regions (CRR) from the M6
      protein. A decrease in the amount of cell surface M6 was observed upon deletion
      of 10 or more amino acid residues at the N terminus. On the other hand,
      reactivity of monoclonal antibody to surface M6 increased with the addition of
      the spacer adjacent to the proline- and glycine-rich region, and an increase in
      epitope dosage was obtained by adding another CRR immediately downstream of the
      original CRR. The results obtained should facilitate the design of improved
      vaccine candidates using this antigen delivery technology.

PMID- 11953385
TI  - Immunization with the RgpA-Kgp proteinase-adhesin complexes of Porphyromonas
      gingivalis protects against periodontal bone loss in the rat periodontitis model.
AB  - A major virulence factor of Porphyromonas gingivalis is the extracellular
      noncovalently associated complexes of Arg-X- and Lys-X-specific cysteine
      proteinases and adhesins designated the RgpA-Kgp complexes. In this study we
      investigated the ability of RgpA-Kgp as an immunogen to protect against P.
      gingivalis-induced periodontal bone loss in the rat. Specific-pathogen-free
      Sprague-Dawley rats were immunized with either formalin-killed whole P.
      gingivalis ATCC 33277 cells with incomplete Freund's adjuvant, RgpA-Kgp with
      incomplete Freund's adjuvant, or incomplete Freund's adjuvant alone. The animals
      were then challenged by oral inoculation with live P. gingivalis ATCC 33277
      cells. Marked periodontal bone loss was observed in animals immunized with
      incomplete Freund's adjuvant alone; this bone loss was significantly (P < 0.05)
      greater than that detected in animals immunized with formalin-killed whole cells
      or RgpA-Kgp or in unchallenged animals. There was no significant difference in
      periodontal bone loss between animals immunized with formalin-killed whole cells
      and those immunized with RgpA-Kgp. The bone loss in these animals was also not
      significantly different from that in unchallenged animals. DNA probe analysis of
      subgingival plaque samples showed that 100% of the animals immunized with
      incomplete Freund's adjuvant alone and challenged with P. gingivalis ATCC 33277
      were positive for the bacterium. However, P. gingivalis ATCC 33277 could not be
      detected in subgingival plaque samples from animals immunized with formalin
      killed whole cells or with RgpA-Kgp. Immunization with formalin-killed whole
      cells or RgpA-Kgp induced a high-titer serum immunoglobulin G2a response. Western
      blot analysis of RgpA-Kgp using pooled protective antisera taken from rats
      immunized with RgpA-Kgp revealed immunodominant bands at 44, 39, and 27 kDa. In
      conclusion, immunization with RgpA-Kgp restricted colonization by P. gingivalis
      and periodontal bone loss in the rat.

PMID- 11953387
TI  - Accumulation of human heat shock protein 60-reactive T cells in the gingival
      tissues of periodontitis patients.
AB  - Heat shock protein 60s (hsp60) are remarkably immunogenic, and both T-cell and
      antibody responses to hsp60 have been reported in various inflammatory
      conditions. To clarify the role of hsp60 in T-cell responses in periodontitis, we
      examined the proliferative response of peripheral blood mononuclear cells (PBMC),
      as well as the cytokine profile and T-cell clonality, for periodontitis patients
      and controls following stimulation with recombinant human hsp60 and Porphyromonas
      gingivalis GroEL. To confirm the infiltration of hsp60-reactive T-cell clones
      into periodontitis lesions, nucleotide sequences within complementarity
      determining region 3 of the T-cell receptor (TCR) beta-chain were compared
      between hsp60-reactive peripheral blood T cells and periodontitis lesion
      infiltrating T cells. Periodontitis patients demonstrated significantly higher
      proliferative responses of PBMC to human hsp60, but not to P. gingivalis GroEL,
      than control subjects. The response was inhibited by anti-major
      histocompatibility complex class II antibodies. Analysis of the nucleotide
      sequences of the TCR demonstrated that human hsp60-reactive T-cell clones and
      periodontitis lesion-infiltrating T cells have the same receptors, suggesting
      that hsp60-reactive T cells accumulate in periodontitis lesions. Analysis of the
      cytokine profile demonstrated that hsp60-reactive PBMC produced significant
      levels of gamma interferon (IFN-gamma) in periodontitis patients, whereas P.
      gingivalis GroEL did not induce any skewing toward a type1 or type2 cytokine
      profile. In control subjects no significant expression of IFN-gamma or
      interleukin 4 was induced. These results suggest that periodontitis patients have
      human hsp60-reactive T cells with a type 1 cytokine profile in their peripheral
      blood T-cell pools.

PMID- 11953388
TI  - Mycoplasma hyopneumoniae increases intracellular calcium release in porcine
      ciliated tracheal cells.
AB  - We investigated the effects of intact pathogenic Mycoplasma hyopneumoniae,
      nonpathogenic M. hyopneumoniae, and Mycoplasma flocculare on intracellular free
      Ca2+ concentrations ([Ca2+]i) in porcine ciliated tracheal epithelial cells. The
      ciliated epithelial cells had basal [Ca2+]i of 103 +/- 3 nM (n = 217 cells). The
      [Ca2+]i increased by 250 +/- 19 nM (n = 47 cells) from the basal level within 100
      s of the addition of pathogenic M. hyopneumoniae strain 91-3 (300 microg/ml), and
      this increase lasted approximately 60 s. In contrast, nonpathogenic M.
      hyopneumoniae and M. flocculare at concentrations of 300 microg/ml failed to
      increase [Ca2+]i. In Ca2+-free medium, pathogenic M. hyopneumoniae still
      increased [Ca2+]i in tracheal cells. Pretreatment with thapsigargin (1 microM for
      30 min), which depleted the Ca2+ store in the endoplasmic reticulum, abolished
      the effect of M. hyoneumoniae. Pretreatment with pertussis toxin (100 ng/ml for 3
      h) or U-73122 (2 microM for 100 s), an inhibitor of phospholipase C, also
      abolished the effect of M. hyopneumoniae. The administration of mastoparan 7, an
      activator of pertussis toxin-sensitive proteins G(i) and G(o), increased [Ca2+]i
      in ciliated tracheal cells. These results suggest that pathogenic M.
      hyopneumoniae activates receptors that are coupled to G(i) or G(o), which in turn
      activates a phospholipase C pathway, thereby releasing Ca2+ from the endoplasmic
      reticulum. Thus, an increase in Ca2+ may serve as a signal for the pathogenesis
      of M. hyopneumoniae.

PMID- 11953389
TI  - A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective
      immunity in BALB/c mice.
AB  - This study was conducted to evaluate the immunogenicity of the Brucella abortus
      lumazine synthase (BLS) gene cloned into the pcDNA3 plasmid, which is driven by
      the cytomegalovirus promoter. Injection of plasmid DNA carrying the BLS gene
      (pcDNA-BLS) into BALB/c mice elicited both humoral and cellular immune responses.
      Antibodies to the encoded BLS included immunoglobulin G1 (IgG1) IgG2a, IgG2b,
      IgG3, and IgM isotypes. Animals injected with pcDNA-BLS exhibited a dominance of
      IgG2a over IgG1. In addition, spleen cells from vaccinated animals produced
      interleukin-2 and gamma interferon but not IL-10 or IL-4 after in vitro
      stimulation with recombinant BLS (rBLS), suggesting the induction of a Th1
      response. Protection was evaluated by comparing the levels of infection in the
      spleens of vaccinated mice challenged with B. abortus 544. Immunization with
      pcDNA-BLS- reduced the bacterial burden relative to those in the control groups.
      Mice immunized with rBLS produced a significant humoral response but did not show
      a specific cellular response or any protection from challenge. Altogether, these
      data suggest that pcDNA-BLS is a good immunogen for the production of humoral and
      cell-mediated responses in mice and is a candidate for use in future studies of
      vaccination against brucellosis.

PMID- 11953390
TI  - Hydrolysis of epithelial junctional proteins by Porphyromonas gingivalis
      gingipains.
AB  - Porphyromonas gingivalis has been implicated as an etiologic agent of adult
      periodontitis. We have previously shown that P. gingivalis can degrade the
      epithelial cell-cell junction complexes, thus suggesting that this bacterium can
      invade the underlying connective tissues via a paracellular pathway. However, the
      precise mechanism(s) involved in this process has not been elucidated. The
      purpose of this study was to determine if the arginine- and lysine-specific
      gingipains of P. gingivalis (i.e., HRgpA and RgpB, and Kgp, respectively) were
      responsible for the degradation of E-cadherin, the cell-cell adhesion protein in
      the adherens junctions. In addition, we compared the degradative abilities of the
      whole gingipains HRgpA and Kgp to those of their catalytic domains alone. In
      these studies, immunoprecipitated E-cadherin as well as monolayers of polarized
      Madin-Darby canine kidney (MDCK) epithelial cell cultures were incubated with the
      gingipains and hydrolysis of E-cadherin was assessed by Western blot analysis.
      Incubation of P. gingivalis cells with immunoprecipitated E-cadherin resulted in
      degradation, whereas prior exposure of P. gingivalis cells to leupeptin and
      especially acetyl-Leu-Val-Lys-aldehyde (which are arginine- and lysine-specific
      inhibitors, respectively) reduced this activity. Furthermore, incubation of E
      cadherin immunoprecipitates with the different gingipains resulted in an
      effective and similar hydrolysis of the protein. However, when monolayers of MDCK
      cells were exposed to the gingipains, Kgp was most effective in hydrolyzing the E
      cadherin molecules in the adherens junction. Kgp was more effective than its
      catalytic domain in degrading E-cadherin at 500 nM but not at a lower
      concentration (250 nM). These results suggest that the hemagglutinin domain of
      Kgp plays a role in degradation and that there is a critical threshold
      concentration for this activity. Taken together, these results provide evidence
      that the gingipains, especially Kgp, are involved in the degradation of the
      adherens junction of epithelial cells, which may be important in the invasion of
      periodontal connective tissue by P. gingivalis.

PMID- 11953391
TI  - Modulation of mouse endotoxic fever by complement.
AB  - It was recently reported that the complement system may be critically involved in
      the febrile response of guinea pigs to systemic, particularly intraperitoneally
      (i.p.) injected, lipopolysaccharides (LPS). The present study was designed to
      identify which component(s) of the complement cascade may be specifically
      critical. To this end, we used mice with C3, C5, and CR2 gene deletions. To
      assess preliminarily the suitability of mice for such a study, we replicated our
      earlier studies with guinea pigs. Thus, to verify initially whether complement is
      similarly involved in the febrile response of wild-type (C57BL/6J) mice to i.p.
      LPS (Escherichia coli, 1 microg/mouse), we depleted complement with cobra venom
      factor (CVF; 7 U/mouse, intravenously [i.v.]). These animals did not develop
      fever, whereas the core temperature (T(c)) of CVF vehicle-treated controls rose
      approximately 1 degrees C by 80 min postinjection and then gradually abated over
      the following 2.5 h, confirming the involvement of complement in fever production
      after i.p. LPS injection and the suitability of this species for these studies.
      C3- and C5-sufficient (C3(+/+) and C5(+/+)) mice also developed 1 degrees C
      fevers within 80 min after i.p. LPS (1 or 2 microg/mouse) injection. These fevers
      were totally prevented by CVF (10 U/mouse, i.v.) pretreatment. C3- and C5
      deficient (C3(-/-) and C5(-/-)) mice were also unable to develop T(c) rises after
      i.p. LPS. Both CR2(+/+) and CR2(-/-) mice responded normally to i.p. LPS (1
      microg/mouse). These data indicate that C5, but not C3d acting through CR2, may
      play a critical role in the febrile response of mice to i.p. LPS.

PMID- 11953392
TI  - Role of pneumococcal surface protein C in nasopharyngeal carriage and pneumonia
      and its ability to elicit protection against carriage of Streptococcus
      pneumoniae.
AB  - Previous studies suggested that PspC is important in adherence and colonization
      within the nasopharynx. In this study, we conducted mutational studies to further
      identify the role PspC plays in the pathogenesis of pneumococci. pspC and/or pspA
      was insertionally inactivated in a serotype 2 Streptococcus pneumoniae strain and
      in a serotype 19 S. pneumoniae strain. In the mouse colonization model,
      pneumococcal strains with mutations in pspC were significantly attenuated in
      their abilities to colonize. In a mouse pneumonia model, strains with mutations
      in pspC were unable to infect or multiply within the lung. Using reverse
      transcriptase PCR we were able to demonstrate that pspC is actively transcribed
      in vivo, when the bacteria are growing in the nasal cavity and in the lungs. In
      the bacteremia model, a strain mutated for pspC alone behaved like the wild type,
      but the absence of both pspC and pspA caused accelerated clearance of the
      bacteria. Intranasal immunization with PspC with cholera toxin subunit B as an
      adjuvant protected against intranasal challenge. Evidence was also obtained that
      revertants that spontaneously acquired PspC expression could multiply and
      colonize the nasal tissue. This latter finding strongly indicates that
      pneumococci are actively metabolizing and growing while in the nasopharynx.

PMID- 11953393
TI  - Recombinant Ochrobactrum anthropi expressing Brucella abortus Cu,Zn superoxide
      dismutase protects mice against B. abortus infection only after switching of
      immune responses to Th1 type.
AB  - The members of the genus Brucella are gram-negative, facultatively intracellular
      bacterial pathogens that cause brucellosis in many animal species and humans.
      Although live, attenuated vaccines are available to protect several animal
      species from the disease, there is no safe and effective vaccine for human use.
      Here we report that a bacterium that is closely related to Brucella species,
      Ochrobactrum anthropi, can be used as a vaccine vector for the delivery of
      Brucella antigens to mice, leading to the elicitation of protective immunity
      against brucellosis. Brucella abortus Cu,Zn superoxide dismutase (SOD), a
      protective Brucella antigen, was expressed in large amounts in O. anthropi strain
      49237 by use of the broad-host-range plasmid pBBR1MCS. Neither O. anthropi strain
      49237 nor the recombinant O. anthropi strain 49237SOD, expressing B. abortus
      Cu,Zn SOD, provided protection against virulent Brucella infection in mice.
      Analysis of immune responses indicated that strains 49237 and 49237SOD stimulated
      a mix of Th1 and Th2 type responses in the mice. After the immune response was
      switched to a Th1-biased response by addition of oligonucleotides containing
      unmethylated CpG motifs, both O. anthropi strain 49237 and the recombinant O.
      anthropi strain 49237SOD induced protection in mice. However, the protection
      conferred by strain 49237SOD was significantly better than that induced by the
      parental strain, 49237.

PMID- 11953394
TI  - Identification and characterization of the ESAT-6 homologue of Mycobacterium
      leprae and T-cell cross-reactivity with Mycobacterium tuberculosis.
AB  - In this paper we describe identification and characterization of Mycobacterium
      leprae ESAT-6 (L-ESAT-6), the homologue of M. tuberculosis ESAT-6 (T-ESAT-6). T
      ESAT-6 is expressed by all pathogenic strains belonging to the M. tuberculosis
      complex but is absent from virtually all other mycobacterial species, and it is a
      promising antigen for immunodiagnosis of tuberculosis (TB). Therefore, we
      analyzed whether L-ESAT-6 is a similarly powerful tool for the study of leprosy
      by examining T-cell responses against L-ESAT-6 in leprosy patients, TB patients,
      and exposed or nonexposed healthy controls from areas where leprosy and TB are
      endemic and areas where they are not endemic. L-ESAT-6 was recognized by T cells
      from leprosy patients, TB patients, individuals who had contact with TB patients,
      and healthy individuals from an area where TB and leprosy are endemic but not by
      T cells from individuals who were not exposed to M. tuberculosis and M. leprae.
      Moreover, leprosy patients who were not responsive to M. leprae failed to respond
      to L-ESAT-6. A very similar pattern was obtained with T-ESAT-6. These results
      show that L-ESAT-6 is a potent M. leprae antigen that stimulates T-cell-dependent
      gamma interferon production in a large proportion of individuals exposed to M.
      leprae. Moreover, our results suggest that there is significant cross-reactivity
      between T-ESAT-6 and L-ESAT-6, which has implications for the use of ESAT-6 as
      tool for diagnosis of leprosy and TB in areas where both diseases are endemic.

PMID- 11953395
TI  - Growth of Neisseria gonorrhoeae in the female mouse genital tract does not
      require the gonococcal transferrin or hemoglobin receptors and may be enhanced by
      commensal lactobacilli.
AB  - Neisseria gonorrhoeae is capable of utilizing a variety of iron sources in vitro,
      including human transferrin, human lactoferrin, hemoglobin, hemoglobin
      haptoglobin complexes, heme, and heterologous siderophores. Transferrin has been
      implicated as a critical iron store for N. gonorrhoeae in the human male urethra.
      The demonstration that gonococci can infect the lower genital tracts of estradiol
      treated BALB/c mice in the absence of human transferrin, however, suggests that
      other usable iron sources are present in the murine genital tract. Here we
      demonstrate that gonococcal transferrin and hemoglobin receptor mutants are not
      attenuated in mice, thereby ruling out transferrin and hemoglobin as essential
      for murine infection. An increased frequency of phase variants with the
      hemoglobin receptor "on" (Hg(+)) occurred in ca. 50% of infected mice; this
      increase was temporally associated with an influx of neutrophils and detectable
      levels of hemoglobin in the vagina, suggesting that the presence of hemoglobin in
      inflammatory exudates selects for Hg(+) phase variants during infection. We also
      demonstrate that commensal lactobacilli support the growth of N. gonorrhoeae in
      vitro unless an iron chelator is added to the medium. We hypothesize that
      commensal lactobacilli may enhance growth of gonococci in vivo by promoting the
      solubilization of iron on mucosal surfaces through the production of metabolic
      intermediates. Finally, transferrin-binding lipoprotein (TbpB) was detected on
      gonococci in vaginal smears, suggesting that although gonococci replicate within
      the genital tracts of mice, they may be sufficiently iron-stressed to express
      iron-repressible proteins. In summary, these studies support the potential role
      of nontransferrin, nonhemoglobin iron sources during gonococcal infection of the
      female genital tract.

PMID- 11953396
TI  - Inhibition of apoptosis by gamma interferon in cells and mice infected with
      Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis).
AB  - The effect of gamma interferon (IFN-gamma) on apoptosis due to infection by
      Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis) was
      studied in epithelial cells in culture and in the genital tracts of mice. IFN
      gamma concentrations that induce the formation of aberrant, persistent chlamydiae
      inhibit apoptosis due to C. muridarum infection. In cells treated with an IFN
      gamma concentration that leads to the development of a heterogenous population of
      normal and aberrant Chlamydia vacuoles, apoptosis was inhibited preferentially in
      cells that contained the aberrant vacuoles. The inhibitory effect of IFN-gamma
      appears to be due in part to expression of host cell indoleamine 2,3-dioxygenase
      activity, since inhibition of apoptosis could be partially reversed through
      coincubation with exogenous tryptophan. Apoptotic cells were observed in the
      genital tracts of wild-type mice infected with C. muridarum, and a significantly
      larger number of apoptotic cells was detected in infected IFN-gamma-deficient
      mice. These results suggest that IFN-gamma may contribute to pathogenesis of
      persistent Chlamydia infections in vivo by preventing apoptosis of infected
      cells.

PMID- 11953397
TI  - Glucan is a component of the Mycobacterium tuberculosis surface that is expressed
      in vitro and in vivo.
AB  - The outermost layer of Mycobacterium tuberculosis is composed primarily of two
      polysaccharides, glucan (GC) and arabinomannan. To analyze the surface
      polysaccharide composition of M. tuberculosis, we generated a monoclonal antibody
      (MAb) that binds M. tuberculosis GC and is known as MAb 24c5. Immunofluorescence
      and whole-mount immunoelectron microscopy indicated that GC is on the outermost
      portion of the bacteria. M. tuberculosis strains Erdman and CDC 1551 were
      analyzed for their ability to bind MAb 24c5 after in vitro growth in media with
      and without the detergent Tween 80. MAb 24c5 bound to Erdman and CDC 1551 at all
      culture times with only slightly greater apparent affinity after extended culture
      in the absence of Tween 80, indicating that a stable amount of GC polysaccharide
      antigen is associated with the cell surface of M. tuberculosis. An enzyme-linked
      immunosorbent assay indicated that GC is antigenically similar to glycogen, and
      the amount of GC antigen increased in the media of M. tuberculosis cultures grown
      either with or without the detergent Tween 80. Other nontuberculosis mycobacteria
      have antigenically similar GCs on their surfaces after in vitro growth.
      Inoculation of mice with live bacilli but not inoculation with dead bacilli
      elicited a strong antibody response to GC consistent with production of this
      antigen in vivo. Our results provide a more comprehensive picture of the M.
      tuberculosis cell envelope and the conditions that allow expression of M.
      tuberculosis GC.

PMID- 11953398
TI  - Rickettsia-macrophage interactions: host cell responses to Rickettsia akari and
      Rickettsia typhi.
AB  - The existence of intracellular rickettsiae requires entry, survival, and
      replication in the eukaryotic host cells and exit to initiate new infection.
      While endothelial cells are the preferred target cells for most pathogenic
      rickettsiae, infection of monocytes/macrophages may also contribute to the
      establishment of rickettsial infection and resulting pathogenesis. We initiated
      studies to characterize macrophage-Rickettsia akari and -Rickettsia typhi
      interactions and to determine how rickettsiae survive within phagocytic cells.
      Flow cytometry, microscopic analysis, and LDH release demonstrated that R. akari
      and R. typhi caused negligible cytotoxicity in mouse peritoneal macrophages as
      well as in macrophage-like cell line, P388D1. Host cells responded to rickettsial
      infection with increased secretion of proinflammatory cytokines such as
      interleukin-1beta (IL-1beta) and IL-6. Furthermore, macrophage infection with R.
      akari and R. typhi resulted in differential synthesis and expression of IL-beta
      and IL-6, which may correlate with the existence of biological differences among
      these two closely related bacteria. In contrast, levels of gamma interferon (IFN
      gamma), IL-10, and IL-12 in supernatants of infected P388D1 cells and mouse
      peritoneal macrophages did not change significantly during the course of
      infection and remained below the enzyme-linked immunosorbent assay cytokine
      detection limits. In addition, differential expression of cytokines was observed
      between R. akari- and R. typhi-infected macrophages, which may correlate with the
      biological differences among these closely related bacteria.

PMID- 11953399
TI  - Molecular analysis of the contribution of the capsular polysaccharide and the
      lipopolysaccharide O side chain to the virulence of Klebsiella pneumoniae in a
      murine model of pneumonia.
AB  - Klebsiella pneumoniae is a common cause of gram-negative bacterial nosocomial
      pneumonia. Two surface polysaccharides, lipopolysaccharide (LPS) O side chain and
      capsular polysaccharide (CPS), are critical for the microorganism in causing
      sepsis, but little is known about their role in pneumonia. To investigate their
      contribution in the pathogenesis of K. pneumoniae pneumonia, we characterized the
      host response to bacterial challenge with a highly virulent clinical isolate or
      with isogenic insertion-duplication mutants deficient in CPS or LPS O side chain
      in a murine model of pneumonia. Animals challenged intratracheally with the wild
      type or LPS O side chain-deficient strain developed pneumonia and became
      bacteremic before death. Extensive lung lesions as well as pleuritis, vasculitis,
      and edema were observed by histopathological examination, and polymorphonuclear
      infiltration was also demonstrated. In contrast, none of the animals challenged
      with the unencapsulated strain developed pneumonia or bacteremia. Examination of
      tissue from this group did not identify lung lesions, and none of the infected
      animals died. Analysis of the early host defense mechanisms that contributed to
      the clearance of the unencapsulated mutant showed that the levels of C3 deposited
      on the unencapsulated mutant surface were threefold higher than those for the
      wild-type and LPS O side chain-deficient strains. Furthermore, phagocytosis of
      the unencapsulated mutant by human alveolar macrophages (AM) was more efficient
      than that of the wild-type and LPS O side chain-deficient strains. We conclude
      that CPS, but not LPS O side chain, is essential for Klebsiella pneumonia because
      it modulates the deposition of C3 and protects the microorganisms against human
      AM phagocytosis.

PMID- 11953400
TI  - Enhanced disease severity in Helicobacter pylori-infected mice deficient in Fas
      signaling.
AB  - Recent evidence suggests that immune-mediated gastric epithelial cell apoptosis
      through Fas-Fas ligand interactions participates in Helicobacter pylori disease
      pathogenesis. To define the role of Fas signaling in vivo, H. pylori strain SS1
      infection in C57BL/6 mice was compared to that in mice deficient in the Fas
      ligand (gld). gld mice had a degree of gastritis similar to that of C57BL/6 mice
      after 6 weeks (gastritis score, 5.2 +/- 0.6 [mean +/- standard error] versus 3.5
      +/- 0.8) and 12 weeks (4.0 +/- 0.7 versus 3.4 +/- 0.5) of infection. Bacterial
      colonization was comparable in each group of mice at 12 weeks of infection (2.1
      +/- 0.3 versus 1.6 +/- 0.3 for gld and C57BL/6, respectively; the difference is
      not significant). Sixty-seven percent of H. pylori-infected gld mice displayed
      atrophic changes in the gastric mucosa, compared with 37% of infected C57BL/6
      mice, at 12 weeks. In addition, atrophic changes were more severe in H. pylori
      infected gld mice (P < 0.05). Splenocytes isolated from H. pylori-infected
      C57BL/6 mice had a twofold increase in production of the Th1 cytokine gamma
      interferon (IFN-gamma) in response to H. pylori antigens at both 6 and 12 weeks
      compared to controls (143 +/- 65 versus 69 +/-26 pg/ml and 336 +/- 73 versus 172
      +/- 60, respectively). In contrast, there was a lack of detectable IFN-gamma in
      gld mice infected with the bacterium. H. pylori-infected C57BL/6 mice had
      increased epithelial cell apoptosis compared with sham-infected C57BL/6 mice
      (35.0 +/- 8.9 versus 12.3 +/- 6.9; P < 0.05). Epithelial cell apoptosis did not
      differ between H. pylori-infected and control gld mice (5.2 +/- 1.6 versus 6.5 +/
      2.9 [not significant]). These data demonstrate that mice with mutations in the
      Fas ligand develop more severe premalignant mucosal changes in response to
      infection with H. pylori in association with both an impaired gastric epithelial
      cell apoptotic response and IFN-gamma production. The Fas death pathway modulates
      disease pathophysiology following murine infection with H. pylori. Deregulation
      of the Fas pathway could be involved in the transition from gastritis to gastric
      cancers during H. pylori infection.

PMID- 11953401
TI  - Immunoglobulin G monoclonal antibodies to Cryptococcus neoformans protect mice
      deficient in complement component C3.
AB  - Passive administration of monoclonal antibodies (MAbs) to the capsular
      polysaccharide of Cryptococcus neoformans can alter the course of infection in
      mice. In a murine model of cryptococcal infection, immunoglobulin G1 (IgG1),
      IgG2a, and IgG2b switch variants of the anti-capsular 3E5 MAb prolong the
      survival of lethally infected mice, whereas the 3E5 IgG3 MAb does not protect and
      in some cases enhances infection, shortening the life spans of infected mice. We
      examined the role of complement component C3 in Ab-mediated protection by
      determining the efficacy of the four mouse IgG subclasses against C. neoformans
      in mice genetically deficient in factor C3 as well as mice acutely depleted of
      C3. Similar to other complement-deficient animal models, C3(-/-) mice and mice
      depleted of C3 by cobra venom factor were more susceptible to C. neoformans
      infection than control mice, providing further evidence that complement is
      important in the host defense against the fungus. In the absence of C3, all IgG
      isotypes prolonged the lives of mice infected with C. neoformans, indicating that
      protection by IgG does not require the complement pathways. Furthermore, we
      observed protection with IgG3 in the complement-deficient mice, suggesting that
      complement is involved in the lack of protection observed with IgG3 in other
      mouse models.

PMID- 11953402
TI  - Chlamydia trachomatis disrupts N-cadherin-dependent cell-cell junctions and
      sequesters beta-catenin in human cervical epithelial cells.
AB  - The cadherin/catenin complex serves as an important structural component of
      adherens junctions in epithelial cells. Under certain conditions, beta-catenin
      can be released from this complex and interact with transcription factors in the
      nucleus to stimulate the expression of genes that regulate apoptosis and cell
      cycle control. While studying the effects of the bacterial pathogen Chlamydia
      trachomatis on human cervical epithelial cells in culture, we observed that C.
      trachomatis caused the epithelial cells to separate from each other without
      detaching from their growing surface. The objective of the present study was to
      determine if this effect might involve the disruption of the cadherin/catenin
      complex. Primary cultures of human cervical epithelial cells or HeLa cells were
      infected with C. trachomatis serovar E. Cadherin-like immunoreactive materials
      and beta-catenin were visualized by immunofluorescence. Preliminary studies
      showed that N-cadherin was the primary cadherin expressed in both the primary
      cultures and the HeLa cells. In noninfected cells, N-cadherin and beta-catenin
      were colocalized at the intercellular junctional complexes. By contrast, the
      infected cells showed a marked loss of both N-cadherin and beta-catenin labeling
      from the junctional complexes and the concomitant appearance of intense beta
      catenin labeling associated with the chlamydial inclusion. The results of Western
      blot analyses of extracts of C. trachomatis showed no evidence of cross
      reactivity with the beta-catenin antibody. These results indicate that C.
      trachomatis causes the breakdown of the N-cadherin/beta-catenin complex and that
      the organism can sequester beta-catenin within the chlamydial inclusion. This
      could represent an important mechanism by which C. trachomatis alters epithelial
      cell function.

PMID- 11953403
TI  - A superoxide-hypersusceptible Salmonella enterica serovar Typhimurium mutant is
      attenuated but regains virulence in p47(phox-/-) mice.
AB  - Salmonella enterica serovar Typhimurium is a gram-negative, facultative
      intracellular pathogen that predominantly invades mononuclear phagocytes and is
      able to establish persistent infections. One of the innate defense mechanisms of
      phagocytic cells is the production of reactive oxygen species, including
      superoxide. S. enterica serovar Typhimurium has evolved mechanisms to resist such
      radicals, and these mechanisms could be decisive in its ability to survive and
      replicate within macrophages. Recently, we described a superoxide
      hypersusceptible S. enterica serovar Typhimurium mutant strain, DLG294, that
      carries a transposon in sspJ, resulting in the lack of expression of SspJ, which
      is necessary for resistance against superoxide and replication within
      macrophages. Here we show that DLG294, which is a 14028s derivative, hardly
      induced any granulomatous lesions in the livers upon subcutaneous infection of
      C3H/HeN (Ity(r)) mice with 3 x 10(4) bacteria and that its bacterial counts were
      reduced by 3 log units compared to those of wild-type S. enterica serovar
      Typhimurium 14028s on day 5 after infection. In contrast, DLG294 replicated like
      wild-type S. enterica serovar Typhimurium 14028s and induced a phenotypically
      similar liver pathology in p47(phox-/-) mice, which are deficient in the
      p47(phox) subunit of the NADPH oxidase complex and which do not produce
      superoxide. Consistent with these results, DLG294 reached bacterial counts
      identical to those of wild-type S. enterica serovar Typhimurium 14028s in bone
      marrow-derived macrophages from p47(phox-/-) mice and in X-CGD PLB-985 cells at
      24 h after challenge. These results indicate that SspJ plays a role in the
      bacterium's resistance to oxidative stress and in the survival and replication of
      S. enterica serovar Typhimurium both in vitro and in vivo.

PMID- 11953404
TI  - Construction and characterization of an acapsular mutant of Mannheimia
      haemolytica A1.
AB  - The nmaA and nmaB genes, which code for UDP-GlcNAc-2-epimerase and UDP-ManNAc
      dehydrogenase, respectively, are involved in capsular polysaccharide biosynthesis
      in Mannheimia haemolytica A1. A chloramphenicol resistance (Cm(r)) cassette
      cloned behind an M. haemolytica A1 promoter, plpcat, was created and used to
      interrupt nmaA and nmaB. A 1.3-kbp DNA fragment that encompasses part of nmaA and
      nmaB was replaced by the 1.0-kbp plpcat, resulting in a knockout mutant which is
      Cm(r) and unable to synthesize N-acetylmannosamine (ManNAc) and N
      acetylmannosaminuronic acid (ManNAcA). The DNA replacement was confirmed by
      Southern hybridization and PCR analyses of the nmaA and nmaB loci. Electron
      microscopy examination of the mutant showed the absence of capsular materials
      compared to the parent strain. The loss of NmaA and NmaB activity was confirmed
      by analysis of carbohydrate moieties using capillary electrophoresis. Serum
      sensitivity assays indicated that the acapsular mutant is as resistant as the
      encapsulated parent to complement-mediated killing by colostrum-deprived calf
      serum but is more sensitive to killing by immune bovine serum. Analysis of
      lipopolysaccharide prepared from the acapsular mutant and encapsulated parent
      confirmed that these strains have long O-polysaccharide chains, possibly
      conferring resistance to serum-mediated killing.

PMID- 11953405
TI  - Gastritis and hypergastrinemia due to Acinetobacter lwoffii in mice.
AB  - In mouse models and humans, Helicobacter pylori is associated with an increase in
      serum gastrin and gastrin-expressing (G) cells with a concomitant decrease in
      somatostatin-expressing D cells. Inflammation of the gastric mucosa can progress
      to metaplastic changes in the stomach and to decreased colonization by H. pylori
      and increased colonization by non-H. pylori organisms. In addition, about 20% of
      individuals with chronic gastritis are H. pylori negative, suggesting that other
      organisms may induce gastritis. Consistent with this hypothesis, we report here
      that Acinetobacter lwoffii causes the same histologic changes as does H. pylori.
      Gastric epithelial cells were isolated from the entire stomach by an enzymatic
      method for quantitation by both flow cytometry and morphometric analysis. Two
      months after mice were inoculated with H. pylori or A. lwoffii, the mucosal T-
      and B-cell numbers significantly increased. After 4 months of infection, there
      was a threefold increase in the number of G cells and a doubling in the number of
      parietal cells. A threefold decrease in the number of D cells occurred in H.
      pylori- and A. lwoffii-infected mice. Plasma gastrin levels increased after both
      H. pylori and A. lwoffii infection. Histology revealed the presence of
      inflammation in the gastric mucosa with both A. lwoffii and H. pylori infection.
      A periodic acid-Schiff stain-alcian blue stain revealed mucous gland metaplasia
      of the corpus. Collectively, the results demonstrate that gastritis and
      hypergastrinemia are not specific for H. pylori but can be induced by other gram
      negative bacteria capable of infecting the mouse stomach.

PMID- 11953406
TI  - Biofilm formation and interaction with the surfaces of gallstones by Salmonella
      spp.
AB  - Salmonellae can exist in an asymptomatic carrier state in the human gallbladder.
      Individuals with gallstones are more likely to become typhoid carriers, and
      antibiotic treatments are often ineffectual against Salmonella enterica serovar
      Typhi in carriers with gallstones. Therefore, we hypothesized that Salmonella
      spp. form biofilms on the surfaces of gallstones, where the bacteria are
      protected from high concentrations of bile and antibiotics. A number of methods
      were utilized to examine biofilm formation on human gallstones and glass
      coverslips in vitro, including confocal, light, and scanning electron microscopy.
      In our assays, salmonellae formed full biofilms on the surfaces of gallstones
      within 14 days and appeared to excrete an exopolysaccharide layer that bound them
      to the surfaces and to other bacteria. Efficient biofilm formation on gallstones
      was dependent upon the presence of bile, as a biofilm did not form on gallstones
      within 14 days in Luria-Bertani broth alone. The biofilms formed by a Salmonella
      enterica serovar Typhi Vi antigen mutant, as well as strains with mutations in
      genes that eliminate production of four different fimbriae, were
      indistinguishable from the biofilms formed by the parents. Mutants with an
      incomplete O-antigen, mutants that were nonmotile, and mutants deficient in
      quorum sensing were unable to develop complete biofilms. In addition, there
      appeared to be selectivity in salmonella binding to the gallstone surface that
      did not depend on the topology or surface architecture. These studies should aid
      in the understanding of the Salmonella carrier state, an important but
      underresearched area of typhoid fever pathogenesis. If the basis of carrier
      development can be understood, it may be possible to identify effective
      strategies to prevent or treat this chronic infection.

PMID- 11953407
TI  - Polarized expression of Tamm-Horsfall protein by renal tubular epithelial cells
      activates human granulocytes.
AB  - In renal bacterial infections granulocytes are of major importance in the primary
      immune defense against invading pathogens. However, the mechanisms of
      granulocytic activation in renal interstitial invasion have not been clarified.
      Renal tubular epithelial cell mechanisms inducing granulocytic activation and
      bacterial killing may include tubular cell expression of Tamm-Horsfall protein
      (THP), a urinary protein that is known to enhance cytokine expression in
      monocytes. We studied the role of THP in granulocytic activation. A strong
      binding of THP to human granulocytes was demonstrated by fluorescence-activated
      cell sorter analysis. Urinary THP and supernatants of THP-expressing cultured
      tubular epithelial cells (MDCK) enhanced interleukin-8 (IL-8) expression by human
      granulocytes. Renal tubular cells growing polarized on polycarbonate membranes
      were used to study apical versus basal THP expression. By electron microscopy THP
      immunoreactivity was exclusively found on the apical surfaces of tubular cells
      and was absent on the basolateral cell membrane. In the apical cell culture
      compartment we found significantly more stimulatory activity for granulocytic IL
      8 expression. CD62L, a selectin less expressed in activated granulocytes, was
      decreased in granulocytes incubated with urinary THP and in supernatants of THP
      producing renal tubular cells but not in supernatants from THP-negative cells.
      Again, the effect on CD62L expression was found only in apical culture media and
      was absent in the basal compartment. In summary our data give evidence that renal
      tubular cell THP expression may be relevant in kidney diseases since THP is a
      potent activator of human granulocytes. The regulation of apical versus basal THP
      expression and release in vivo may be crucial in the induction of the
      inflammatory response, e.g., in bacterial renal diseases.

PMID- 11953409
TI  - The cytolethal distending toxin of Haemophilus ducreyi inhibits endothelial cell
      proliferation.
AB  - Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease
      chancroid, produces a cytolethal distending toxin (HdCDT) that inhibits mammalian
      cell proliferation. We investigated the effects of HdCDT on normal human
      endothelial cells and on tubule formation in an in vitro model of angiogenesis.
      Endothelial cells were arrested in the G2 phase of the cell cycle, and tubule
      formation was inhibited in a dose-dependent manner. The antiproliferative
      activities of HdCDT on endothelial cells might contribute to the characteristic
      slow healing and persistence of chancroid ulcers.

PMID- 11953408
TI  - Listeria monocytogenes infection in caspase-11-deficient mice.
AB  - Caspase-11 (Cas11) is a cysteine protease involved in programmed cell death and
      cytokine maturation. Through activation of Cas1 (interleukin-1beta [IL-1beta]
      converting enzyme), Cas11 is directly involved in the maturation of IL-1beta and
      IL-18. Apoptosis is mediated through Cas3. Given the role of apoptosis and
      cytokine signaling during the innate immune response in intracellular infection,
      we examined Cas11-deficient (Cas11(-/-)) mice during infection with Listeria
      monocytogenes. Cas11(-/-) and wild-type C57BL/6 mice were equally susceptible to
      intravenous infection with L. monocytogenes, resulting in similar bacterial
      burdens in tissue and similar survival rates. By contrast, enhanced
      susceptibility was observed in control mice on a mixed genetic 129/C57BL/DBA2
      background. Cas11(-/-) and wild-type mice infected with Listeria had similar
      hepatic microabscess formation in terms of histologic appearance, size, and
      number. Apoptosis of L. monocytogenes-infected hepatocytes in vivo and in vitro
      in primary culture was not altered by the absence of Cas11. Serum IL-18 and IL
      1beta levels were similar in Cas11(-/-) mice and controls. Endotoxin
      (lipopolysaccharide [LPS])-challenged Cas11(-/-) mice were deficient in the
      production of gamma interferon. IL-1beta responses in Cas11(-/-) were normal with
      intravenous administration of LPS but decreased with intraperitoneal
      administration. Our findings suggest that Cas11 deficiency does not impair the
      immune response to infection with L. monocytogenes. Apoptosis and maturation of
      IL-18 and IL-1beta were normal despite Cas11 deficiency. LPS-induced
      proinflammatory pathways are altered by the absence of Cas11. While Cas11
      mediated Cas1 and Cas3 activation is crucial for cytokine maturation and
      apoptosis during inflammation, alternative pathways allow normal inflammatory and
      apoptotic responses during infection with L. monocytogenes.

PMID- 11953410
TI  - Fibronectin attachment protein is necessary for efficient attachment and invasion
      of epithelial cells by Mycobacterium avium subsp. paratuberculosis.
AB  - Attachment and ingestion of Mycobacterium avium subsp. paratuberculosis by two
      epithelial cell lines were enhanced by soluble fibronectin (FN). Peptide blocking
      of the FN attachment protein (FAP-P) inhibited the internalization of M. avium
      subsp. paratuberculosis. Disruption of FAP-P expression significantly reduced
      attachment and ingestion of M. avium subsp. paratuberculosis by T-24 and Caco-2
      cells. The results indicate that the interaction between FN and FAP-P facilitates
      attachment and internalization of M. avium subsp. paratuberculosis by epithelial
      cells.

PMID- 11953411
TI  - Induction of protective immunity to Listeria monocytogenes by immunization with
      plasmid DNA expressing a helper T-cell epitope that replaces the class II
      associated invariant chain peptide of the invariant chain.
AB  - Listeria epitope-specific helper T (Th) cells were able to be primed and induced
      in vivo by immunization with a plasmid carrying an invariant chain (Ii) gene
      whose class II-associated invariant chain peptide (CLIP) region was replaced by a
      Listeria Th epitope. Immunization of C3H/He mice with an Ii-LLO 215-226 plasmid
      induced specific interferon-gamma- and interleukin 2-producing Th cells and
      conferred significant protective immunity against listerial infection.

PMID- 11953412
TI  - Afa, a diffuse adherence fibrillar adhesin associated with enteropathogenic
      Escherichia coli.
AB  - O55 is one of the most frequent enteropathogenic Escherichia coli (EPEC) O
      serogroups implicated in infantile diarrhea in developing countries. Multilocus
      enzyme electrophoresis analysis showed that this serogroup includes two major
      electrophoretic types (ET), designated ET1 and ET5. ET1 corresponds to typical
      EPEC, whilst ET5 comprises strains with different combinations of virulence
      genes, including those for localized adherence (LA) and diffuse adherence (DA).
      Here we report that ET5 DA strains possess a DA adhesin, designated EPEC Afa. An
      11.6-kb chromosomal region including the DA adhesin operon from one O55:H(-) ET5
      EPEC strain was sequenced and found to encode a protein with 98% identity to AfaE
      1, an adhesin associated with uropathogenic E. coli. Although described as an
      afimbrial adhesin, we show that both AfaE-1 and EPEC Afa possess fine fibrillar
      structures. This is the first characterization and demonstration of an Afa
      adhesin associated with EPEC.

PMID- 11953413
TI  - Gamma interferon fails to induce expression of indoleamine 2,3-dioxygenase and
      does not control the growth of Chlamydophila abortus in BeWo trophoblast cells.
AB  - The BeWo trophoblast cell line does not constitutively express the tryptophan
      degrading enzyme indolamine 2,3-dioxygenase (IDO), nor can IDO expression be
      induced by gamma interferon. This correlates with the inability of BeWo cells to
      control the growth of Chlamydophila abortus, in contrast to effects observed in
      HeLa cells treated with gamma interferon.

PMID- 11953414
TI  - Genomic analysis of the F3031 Brazilian purpuric fever clone of Haemophilus
      influenzae biogroup aegyptius by PCR-based subtractive hybridization.
AB  - PCR-based subtractive genome hybridization produced clones harboring inserts
      present in Brazilian purpuric fever (BPF) prototype strain F3031 but absent in
      noninvasive Haemophilus influenzae biogroup aegyptius isolate F1947. Some of
      these inserts have no matches in the GenBank database, while others are similar
      to genes encoding either known or hypothetical proteins. One insert represents a
      2.3-kb locus with similarity to a Thermotoga maritima hypothetical protein, while
      another is part of a 7.6-kb locus that contains predicted genes encoding
      hypothetical, phage-related, and carotovoricin Er-like proteins. The presence of
      DNA related to these loci is variable among BPF isolates and nontypeable H.
      influenzae strains, while neither of them was detected in strains of types a to
      f. The data indicate that BPF-causing strain F3031 harbors unique chromosomal
      regions, most of which appear to be acquired from unrelated microbial sources.

PMID- 11953415
TI  - Identification and functional analysis of an immunoreactive DsbA-like thio
      disulfide oxidoreductase of Ehrlichia spp.
AB  - Novel homologous DsbA-like disulfide bond formation (Dsb) proteins of Ehrlichia
      chaffeensis and Ehrlichia canis were identified which restored DsbA activity in
      complemented Escherichia coli dsbA mutants. Recombinant Ehrlichia Dsb (eDsb)
      proteins were recognized by sera from E. canis-infected dogs but not from E.
      chaffeensis-infected patients. The eDsb proteins were observed primarily in the
      periplasm of E. chaffeensis and E. canis.

PMID- 11953416
TI  - Intimin facilitates colonization by Escherichia coli O157:H7 in adult ruminants.
AB  - We compared the magnitude and duration of fecal shedding of wild-type Escherichia
      coli O157:H7 to that of an isogenic intimin mutant in young adult cattle and
      sheep. In both ruminant species, wild-type E. coli O157:H7 was shed in greater
      numbers and for a longer duration than was the intimin mutant.

PMID- 11953417
TI  - Yersinia pseudotuberculosis produces a cytotoxic necrotizing factor.
AB  - Cell extracts from Yersinia pseudotuberculosis induced multinucleation in HEp-2
      cells in a manner similar to the effect caused by Escherichia coli cytotoxic
      necrotizing factor (CNF). The activity was not dependent on the Yersinia 70-kb
      virulence plasmid, and the activity was not inhibited by antibodies capable of
      neutralizing E. coli CNF type 1. The nucleotide sequence of the Yersinia cnf gene
      was 65.1% identical to the E. coli cnf gene.

PMID- 11953418
TI  - Differential persistence among genomovars of the Burkholderia cepacia complex in
      a murine model of pulmonary infection.
AB  - Cystic fibrosis patients infected with strains from different genomovars of the
      Burkholderia cepacia complex can experience diverse clinical outcomes. To
      identify genomovar-specific determinants that might be responsible for these
      differences, we developed a pulmonary model of infection in BALB/c mice. Mice
      were rendered leukopenic by administration of cyclophosphamide prior to
      intranasal challenge with 1.6 x 10(4) bacteria. Five of six genomovar II strains
      persisted at stable numbers in the lungs until day 16 with minimal toxicity,
      whereas zero of seven genomovar III strains persisted but resulted in variable
      toxicity. We have developed a chronic pulmonary model of B. cepacia infection
      which reveals differences among genomovars in terms of clinical infection
      outcome.

PMID- 11953419
TI  - Passive immunization with bovine milk containing antibodies to a cell surface
      protein antigen-glucosyltransferase fusion protein protects rats against dental
      caries.
AB  - Cell surface protein antigen (PAc) and glucosyltransferases (GTF) of
      Streptococcus mutans are major colonization factors of the organism. We prepared
      bovine milk containing antibodies against a fusion of the saliva-binding alanine
      rich region of PAc with the glucan-binding domain of GTF-I. This study examined
      the effect of the immune milk on the cariogenicity of S. mutans in a rat model.
      Concentrated immune milk was fed to rats once a day for 55 days. The group that
      received immune milk had significantly less caries development than controls.

PMID- 11953420
TI  - Intravaginal and intranasal immunizations are equally effective in inducing
      vaginal antibodies and conferring protection against vaginal candidiasis.
AB  - Oophorectomized, estrogen-treated rats were immunized by the intravaginal or
      intranasal route with a mannoprotein extract (MP) or secreted aspartyl
      proteinases (Sap) of Candida albicans, with or without cholera toxin as a mucosal
      adjuvant. Both routes of immunization were equally effective in (i) inducing anti
      MP and anti-Sap vaginal antibodies and (ii) conferring a high degree of
      protection against the vaginal infection by the fungus. These data suggest that
      appropriate fungal antigens and adjuvant can be used to protect against candidal
      vaginitis, by either route.

PMID- 11953421
TI  - Autonomous expression of the slo gene of the bicistronic nga-slo operon of
      Streptococcus pyogenes.
AB  - A recent model for cytolysin-mediated translocation in Streptococcus pyogenes
      proposes that NAD-glycohydrolase is translocated through streptolysin O-generated
      pores into a host cell (J. Madden, N. Ruiz, and M. Caparon, Cell 104:143-152,
      2001). This model also assumes that the NAD-glycohydrolase (nga) and streptolysin
      O (slo) genes that code for these products are organized in an operon-like
      structure expressed from a single promoter only (nga). We expand this model by
      showing that slo possesses its own autonomous promoter, which is located 155 bp
      upstream of the slo gene. Under experimental conditions in which S. pyogenes is
      grown in THY medium, the strength of the slo promoter, as measured by the
      activity of a lacZ reporter gene, resulted in low but highly reproducible values.
      Finally, we demonstrated that sloR, a S. pyogenes gene that closely resembles the
      Clostridium perfringens pfoR gene, exerts a negative effect on the expression of
      the slo gene.

PMID- 11953422
TI  - A lipid core peptide construct containing a conserved region determinant of the
      group A streptococcal M protein elicits heterologous opsonic antibodies.
AB  - The study reported here investigated the immunogenicity and protective potential
      of a lipid core peptide (LCP) construct containing a conserved region determinant
      of M protein, defined as peptide J8. Parenteral immunization of mice with LCP-J8
      led to the induction of high-titer serum immunoglobulin G J8-specific antibodies
      when the construct was coadministered with complete Freund's adjuvant (CFA) or
      administered alone. LCP-J8 in CFA had significantly enhanced immunogenicity
      compared with the monomeric peptide J8 given in CFA. Moreover, LCP-J8/CFA and LCP
      J8 antisera opsonized four different group A streptococcal (GAS) strains, and the
      antisera did not cross-react with human heart tissue proteins. These data
      indicate the potential of an LCP-based M protein conserved region GAS vaccine in
      the induction of broadly protective immune responses in the absence of a
      conventional adjuvant.

PMID- 11953423
TI  - Mutual dependence of MDM2 and MDMX in their functional inactivation of p53.
AB  - MDMX, an MDM2-related protein, has emerged as yet another essential negative
      regulator of p53 tumor suppressor, since loss of MDMX expression results in p53
      dependent embryonic lethality in mice. However, it remains unknown why neither
      homologue can compensate for the loss of the other. In addition, results of
      biochemical studies have suggested that MDMX inhibits MDM2-mediated p53
      degradation, thus contradicting its role as defined in gene knockout experiments.
      Using cells deficient in either MDM2 or MDMX, we demonstrated that these two p53
      inhibitors are in fact functionally dependent on each other. In the absence of
      MDMX, MDM2 is largely ineffective in down-regulating p53 because of its extremely
      short half-life. MDMX renders MDM2 protein sufficiently stable to function at its
      full potential for p53 degradation. On the other hand, MDMX, which is a
      cytoplasmic protein, depends on MDM2 to redistribute into the nucleus and be able
      to inactivate p53. We also showed that MDMX, when exceedingly overexpressed,
      inhibits MDM2-mediated p53 degradation by competing with MDM2 for p53 binding.
      Our findings therefore provide a molecular basis for the nonoverlapping
      activities of these two p53 inhibitors previously revealed in genetic studies.

PMID- 11953425
TI  - Modulation of the catalytic activity of neutrophil collagenase MMP-8 on bovine
      collagen I. Role of the activation cleavage and of the hemopexin-like domain.
AB  - The cleavage of bovine collagen I by neutrophil collagenase MMP-8 has been
      followed at pH 7.4, 37 degrees C. The behavior of the whole enzyme molecule
      (whMMP-8), displaying both the catalytic domain and the hemopexin-like domain,
      has been compared under the same experimental conditions with that of the
      catalytic domain only. The main observation is that whMMP-8 cleaves bovine
      collagen I only at a single specific site, as already reported by many others
      (Mallya, S. K., Mookhtiar, K. A., Gao, Y., Brew, K., Dioszegi, M., Birkedal
      Hansen, H., and van Wart, H. E. (1990) Biochemistry 29, 10628-10634; Knauper, V.,
      Osthues, A., DeClerk, Y. A., Langley, K. A., Blaser, J., and Tschesche, H. (1993)
      Biochem. J. 291, 847-854; Marini, S., Fasciglione, G. F., De Sanctis, G.,
      D'Alessio, S., Politi, V., and Coletta, M. (2000) J. Biol. Chem. 275, 18657
      18663), whereas the catalytic domain lacks this specificity and cleaves the
      collagen molecule at multiple sites. Furthermore, a meaningful difference is
      observed for the cleavage features displayed by two forms of the catalytic
      domain, which differ for the N terminus resulting from the activation process
      (i.e. the former Met(80) of the proenzyme (MetMMP-8) and the former Phe(79) of
      the proenzyme (PheMMP-8)). Thus, the PheMMP-8 species is characterized by a much
      faster k(cat)/K(m), fully attributable to a lower K(m), suggesting that the
      conformation of the catalytic domain, induced by the insertion of this N-terminal
      residue in a specific pocket (Reinemer, P., Grams, F., Huber, R., Kleine, T.,
      Schnierer, S., Piper, M., Tschesche, H., and Bode, W. (1994) FEBS Lett. 338, 227
      233), brings about a better, although less discriminatory, recognition process of
      cleavage site(s) on bovine collagen I.

PMID- 11953424
TI  - Human mitochondrial ferritin expressed in HeLa cells incorporates iron and
      affects cellular iron metabolism.
AB  - Mitochondrial ferritin (MtF) is a newly identified ferritin encoded by an
      intronless gene on chromosome 5q23.1. The mature recombinant MtF has a
      ferroxidase center and binds iron in vitro similarly to H-ferritin. To explore
      the structural and functional aspects of MtF, we expressed the following forms in
      HeLa cells: the MtF precursor (approximately 28 kDa), a mutant MtF precursor with
      a mutated ferroxidase center, a truncated MtF lacking the approximately 6-kDa
      mitochondrial leader sequence, and a chimeric H-ferritin with this leader
      sequence. The experiments show that all constructs with the leader sequence were
      processed into approximately 22-kDa subunits that assembled into multimeric
      shells electrophoretically distinct from the cytosolic ferritins. Mature MtF was
      found in the matrix of mitochondria, where it is a homopolymer. The wild type MtF
      and the mitochondrially targeted H-ferritin both incorporated the (55)Fe label in
      vivo. The mutant MtF with an inactivated ferroxidase center did not take up iron,
      nor did the truncated MtF expressed transiently in cytoplasm. Increased levels of
      MtF both in transient and in stable transfectants resulted in a greater retention
      of iron as MtF in mitochondria, a decrease in the levels of cytosolic ferritins,
      and up-regulation of transferrin receptor. Neither effect occurred with the
      mutant MtF with the inactivated ferroxidase center. Our results indicate that
      exogenous iron is as available to mitochondrial ferritin as it is to cytosolic
      ferritins and that the level of MtF expression may have profound consequences for
      cellular iron homeostasis.

PMID- 11953426
TI  - Associations of B- and C-Raf with cholesterol, phosphatidylserine, and lipid
      second messengers: preferential binding of Raf to artificial lipid rafts.
AB  - The serine/threonine kinase C-Raf is a key mediator in cellular signaling.
      Translocation of Raf to membranes has been proposed to be facilitated by Ras
      proteins in their GTP-bound state. In this study we provide evidence that both
      purified B- and C-Raf kinases possess lipophilic properties and associate with
      phospholipid membranes. In the presence of phosphatidylserine and lipid second
      messengers such as phosphatidic acid and ceramides these associations were very
      specific with affinity constants (K(D)) in the range of 0.5-50 nm. Raf
      association with liposomes was accompanied by displacement of 14-3-3 proteins and
      inhibition of Raf kinase activities. Interactions of Raf with cholesterol are of
      particular interest, since cholesterol has been shown to be involved, together
      with sphingomyelin and glycerophospholipids in the formation of specialized lipid
      microdomains called rafts. We demonstrate here that purified Raf proteins have
      moderate binding affinity for cholesterol. However, under conditions of lipid
      raft formation, Raf association with cholesterol (or rafts) increased
      dramatically. Since ceramides also support formation of rafts and interact with
      Raf we propose that Raf may be present at the plasma membrane in two distinct
      microdomains: in raft regions via association with cholesterol and ceramides and
      in non-raft regions due to interaction with phosphatidylserine and phosphatidic
      acid. At either location Raf kinase activity was inhibited by lipid binding in
      the absence or presence of Ras. Ras-Raf interactions with full-length C-Raf were
      studied both in solution and in phospholipid environment. Ras association with
      Raf was GTP dependent as previously demonstrated for C-Raf-RBD fragments. In the
      presence of liposomes the recruitment of C-Raf by reconstituted Ras-farnesyl was
      only marginal, since almost 70% of added C-Raf was bound by the lipids alone.
      Thus Ras-Raf binding in response to activation of Ras-coupled receptors may
      utilize Raf protein that is already present at the membrane.

PMID- 11953427
TI  - Regulation of peroxisome proliferator-activated receptor-gamma-mediated gene
      expression. A new mechanism of action for high density lipoprotein.
AB  - Cellular cholesterol content reflects a balance of lipid influx by lipoprotein
      receptors and endogenous synthesis and efflux to cholesterol acceptor particles.
      The beneficial effect of high density lipoprotein (HDL) in protecting against the
      development of cardiovascular disease is thought to be mediated predominately
      through its induction of cellular cholesterol efflux and "reverse cholesterol
      transport" from peripheral tissues to the liver. We tested the hypothesis that
      HDL could inhibit cellular lipid accumulation by modulating expression of
      peroxisome proliferator-activated receptor-gamma (PPARgamma)-responsive genes. To
      this end, we evaluated expression of two PPARgamma-responsive genes, CD36, a
      receptor for oxidized low density lipoprotein, and aP2, a fatty acid-binding
      protein. HDL decreased expression of macrophage CD36 and aP2 in a dose-dependent
      manner. HDL also decreased aP2 expression in fibroblasts, reduced accumulation of
      lipid, and slowed differentiation of fibroblasts into adipocytes. HDL stimulated
      mitogen-activated protein (MAP) kinase activity, and inhibition of CD36
      expression was blocked by co-incubation with a MAP kinase inhibitor. HDL
      increased expression of PPARgamma mRNA and protein, induced translocation of
      PPARgamma from the cytoplasm to the nucleus, and increased PPARgamma
      phosphorylation. Our data demonstrate that despite induction and translocation of
      PPARgamma in response to HDL, MAP kinase-mediated phosphorylation of PPARgamma
      inhibited expression of PPARgamma-responsive genes and suggest mechanisms by
      which HDL may inhibit cellular lipid accumulation.

PMID- 11953428
TI  - The NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and
      processing of the NF-kappa B precursor p105.
AB  - The p50 subunit of NF-kappaB is generated by limited processing of the precursor
      p105. IkappaB kinase-mediated phosphorylation of the C-terminal domain of p105
      recruits the SCF(beta-TrCP) ubiquitin ligase, resulting in rapid ubiquitination
      and subsequent processing/degradation of p105. NEDD8 is known to activate SCF
      ligases following modification of their cullin component. Here we show that
      NEDDylation is required for conjugation and processing of p105 by SCF(beta-TrCP)
      following phosphorylation of the molecule. In a crude extract, a dominant
      negative E2 enzyme, UBC12, inhibits both conjugation and processing of p105, and
      inhibition is alleviated by an excess of WT- UBC12. In a reconstituted cell-free
      system, ubiquitination of p105 was stimulated only in the presence of all three
      components of the NEDD8 pathway, E1, E2, and NEDD8. A Cul-1 mutant that cannot be
      NEDDylated could not stimulate ubiquitination and processing of p105. Similar
      findings were observed also in cells. It should be noted that NEDDylation is
      required only for the stimulated but not for basal processing of p105. Although
      the mechanisms that underlie processing of p105 are largely obscure, it is clear
      that NEDDylation and the coordinated activity of SCF(beta-TrCP) on both p105 and
      IkappaBalpha serve as an important regulatory mechanism controlling NF-kappaB
      activity.

PMID- 11953429
TI  - The Golgi localization of phosphatidylinositol transfer protein beta requires the
      protein kinase C-dependent phosphorylation of serine 262 and is essential for
      maintaining plasma membrane sphingomyelin levels.
AB  - Recombinant mouse phosphatidylinositol transfer protein (PI-TP)beta is a
      substrate for protein kinase C (PKC)-dependent phosphorylation in vitro. Based on
      site-directed mutagenesis and two-dimensional tryptic peptide mapping, Ser(262)
      was identified as the major site of phosphorylation and Ser(165) as a minor
      phosphorylation site. The phospholipid transfer activities of wild-type PI-TP
      beta and PI-TP beta(S262A) were identical, whereas PI-TP beta(S165A) was
      completely inactive. PKC-dependent phosphorylation of Ser(262) also had no effect
      on the transfer activity of PI-TP beta. To investigate the role of Ser(262) in
      the functioning of PI-TP beta, wtPI-TP beta and PI-TP beta(S262A) were
      overexpressed in NIH3T3 fibroblast cells. Two-dimensional PAGE analysis of cell
      lysates was used to separate PI-TP beta from its phosphorylated form. After
      Western blotting, wtPI-TP beta was found to be 85% phosphorylated, whereas PI-TP
      beta(S262A) was not phosphorylated. In the presence of the PKC inhibitor GF
      109203X, the phosphorylated form of wtPI-TP beta was strongly reduced.
      Immunolocalization showed that wtPI-TP beta was predominantly associated with the
      Golgi membranes. In the presence of the PKC inhibitor, wtPI-TP beta was
      distributed throughout the cell similar to what was observed for PI-TP
      beta(S262A). In contrast to wtPI-TP beta overexpressors, cells overexpressing PI
      TP beta(S262A) were unable to rapidly replenish sphingomyelin in the plasma
      membrane upon degradation by sphingomyelinase. This implies that PKC-dependent
      association with the Golgi complex is a prerequisite for PI-TP beta to express
      its effect on sphingomyelin metabolism.

PMID- 11953431
TI  - Three-dimensional structure of human gamma -glutamyl hydrolase. A class I
      glatamine amidotransferase adapted for a complex substate.
AB  - gamma-Glutamyl hydrolase catalyzes the cleavage of the gamma-glutamyl chain of
      folylpoly-gamma-glutamyl substrates and is a central enzyme in folyl and
      antifolyl poly-gamma-glutamate metabolism. The crystal structure of human gamma
      glutamyl hydrolase, determined at 1.6-A resolution, reveals that the protein is a
      homodimer. The overall structure of human gamma-glutamyl hydrolase contains 11
      alpha-helices and 14 beta-strands, with a fold in which a central eight-stranded
      beta-sheet is sandwiched by three and five alpha-helices on each side. The
      topology is very similar to that of the class I glutamine amidotransferase
      domains, with the only major differences consisting of extensions in four loops
      and at the C terminus. These insertions are important for defining the substrate
      binding cleft and/or the dimer interface. Two sequence motifs are found in common
      between human gamma-glutamyl hydrolase and the class I glutamine amidotransferase
      family and include the catalytically essential residues, Cys-110 and His-220.
      These residues are located in the center of a large l-shaped cleft that is closed
      at one end and open at the other. Several conserved residues, including Glu-114,
      His-171, Gln-218, and Lys-223, may be important for substrate binding. Modeling
      of a methotrexate thioester intermediate, based on the corresponding complex of
      the glutamate thioester intermediate of Escherichia coli carbamoyl-phosphate
      synthetase, indicates that the substrate binds in an orientation with the pteroyl
      group toward the open end of the cleft.

PMID- 11953430
TI  - Gram-negative flagellin-induced self-tolerance is associated with a block in
      interleukin-1 receptor-associated kinase release from toll-like receptor 5.
AB  - Flagellin from a number of Gram-negative bacteria induces cytokine and nitric
      oxide production by inflammatory cell types. In view of the evidence that
      flagellin responsiveness is subject to modulation, we explored the possibilities
      that a prior exposure to flagellin might result in a state of reduced flagellin
      responsiveness or tolerance and that lipopolysaccharide (LPS) and flagellin may
      induce a state of cross-tolerance to each other. Our results demonstrate that a
      prior exposure to flagellin results in a subsequent state of flagellin tolerance
      in human monocytes, THP1 cells, Jurkat cells, and COS-1 cells. Tolerance occurs
      within 2 h after addition of flagellin and does not require protein synthesis.
      Flagellin did not induce tolerance to LPS in monocytes and THP1 cells; however,
      LPS treatment of monocytes and THP1 cells resulted in a state of flagellin cross
      tolerance. Flagellin-induced self-tolerance is not the result of a decrease in
      the steady-state level of toll-like receptor 5 (TLR5) or interleukin-1 receptor
      associated kinase (IRAK), but it is associated with a block in the release of
      IRAK from the TLR5 complex in flagellin-tolerant cells. Release is essential for
      IRAK activity because the TLR5-associated IRAK lacks kinase activity. LPS-induced
      cross-tolerance to flagellin is also associated with a block in IRAK release from
      TLR5. These results provide evidence for a novel mechanism of TLR signaling
      control.

PMID- 11953432
TI  - Abrogation of the S phase DNA damage checkpoint results in S phase progression or
      premature mitosis depending on the concentration of 7-hydroxystaurosporine and
      the kinetics of Cdc25C activation.
AB  - DNA damage causes cell cycle arrest in G(1), S, or G(2) to prevent replication on
      damaged DNA or to prevent aberrant mitosis. The G(1) arrest requires the p53
      tumor suppressor, yet the topoisomerase I inhibitor SN38 induces p53 after the
      G(1) checkpoint such that the cells only arrest in S or G(2). Hence, SN38
      facilitates comparison of p53 wild-type and mutant cells with regard to the
      efficacy of drugs such as 7-hydroxystaurosporine (UCN-01) that abrogate S and
      G(2) arrest. UCN-01 abrogated S and G(2) arrest in the p53 mutant breast tumor
      cell line MDA-MB-231 but not in the p53 wild-type breast line, MCF10a. This
      resistance to UCN-01 in the p53 wild-type cells correlated with suppression of
      cyclins A and B. In the p53 mutant cells, low concentrations of UCN-01 caused S
      phase cells to progress to G(2) before undergoing mitosis and death, whereas high
      concentrations caused rapid premature mitosis and death of S phase cells. UCN-01
      inhibits Chk1/2, which should activate the mitosis-inducing phosphatase Cdc25C,
      yet this phosphatase remained inactive during S phase progression induced by low
      concentrations of UCN-01, probably because Cdc25C is also inhibited by the
      constitutive kinase, C-TAK1. High concentrations of UCN-01 caused rapid
      activation of Cdc25C, which is attributed to inhibition of C-TAK1, as well as
      Chk1/2. Hence, UCN-01 has multiple effects depending on concentration and cell
      phenotype that must be considered when investigating mechanisms of checkpoint
      regulation.

PMID- 11953433
TI  - The major birch allergen, Bet v 1, shows affinity for a broad spectrum of
      physiological ligands.
AB  - Bet v 1 is a 17-kDa protein abundantly present in the pollen of the White birch
      tree and is the primary cause of birch pollen allergy in humans. Its three
      dimensional structure is remarkable in that a solvent-accessible cavity traverses
      the core of the molecule. The biological function of Bet v 1 is unknown, although
      it is homologous to a family of pathogenesis-related proteins in plants. In this
      study we first show that Bet v 1 in the native state is able to bind the
      fluorescent probe 8-anilino-1-naphthalenesulfonic acid (ANS). ANS binds to Bet v
      1 with 1:1 stoichiometry, and NMR data indicate that binding takes place in the
      cavity. Using an ANS displacement assay, we then identify a range of
      physiologically relevant ligands, including fatty acids, flavonoids, and
      cytokinins, which generally bind with low micromolar affinity. The ability of
      these ligands to displace ANS suggests that they also bind in the cavity,
      although the exact binding sites seem to vary among different ligands. The
      cytokinins, for example, seem to bind at a separate site close to ANS, because
      they increase the fluorescence of the ANS. Bet v 1 complex. Also, the fluorescent
      sterol dehydroergosterol binds to Bet v 1 as demonstrated by direct titrations.
      This study provides the first qualitative and quantitative data on the ligand
      binding properties of this important pollen allergen. Our findings indicate that
      ligand binding is important for the biological function of Bet v 1.

PMID- 11953434
TI  - Modular structure of a docking surface on MAPK phosphatases.
AB  - Mitogen-activated protein kinases (MAPKs) must be precisely inactivated to
      achieve proper functions in the cells. Ten members of dual specificity
      phosphatases specifically acting on MAPKs, termed MAPK phosphatases (MKPs), have
      been reported. Each member has its own substrate specificity that should be
      tightly regulated. However, the molecular mechanism underlying the regulation of
      the specificity is largely unknown. In the MAPK signaling pathways, docking
      interactions, which are different from transient enzyme-substrate interaction,
      are known to regulate the enzymatic specificity. Here we have identified and
      characterized a docking surface of MKPs. Our results show that a docking surface
      is composed of a tandem alignment of three subregions (modules): a cluster of
      positively charged amino acids, a cluster of hydrophobic amino acids, and a
      cluster of positively charged amino acids (positive-hydrophobic-positive). This
      modular structure well fits the docking groove on MAPKs that we have previously
      identified and may contribute to regulating the docking specificity of the MKP
      family. The position, number, and species of charged amino acids in each module
      including the central hydrophobic subregion are important factors in regulation
      of docking to specific MAPKs. This modular structure in the docking interaction
      may define a novel model of protein-protein interaction that would also regulate
      other systems.

PMID- 11953435
TI  - PurT-encoded glycinamide ribonucleotide transformylase. Accommodation of
      adenosine nucleotide analogs within the active site.
AB  - PurT-encoded glycinamide ribonucleotide transformylase, or PurT transformylase,
      functions in purine biosynthesis by catalyzing the formylation of glycinamide
      ribonucleotide through a catalytic mechanism requiring Mg(2+)ATP and formate.
      From previous x-ray diffraction analyses, it has been demonstrated that PurT
      transformylase from Escherichia coli belongs to the ATP-grasp superfamily of
      enzymes, which are characterized by three structural motifs referred to as the A
      , B-, and C-domains. In all of the ATP-grasp enzymes studied to date, the
      adenosine nucleotide ligands are invariably wedged between the B- and C-domains,
      and in some cases, such as biotin carboxylase and carbamoyl phosphate synthetase,
      the B-domains move significantly upon nucleotide binding. Here we present a
      systematic and high-resolution structural investigation of PurT transformylase
      complexed with various adenosine nucleotides or nucleotide analogs including
      Mg(2+)ATP, Mg(2+)-5'-adenylylimidodiphosphate, Mg(2+)-beta,gamma
      methyleneadenosine 5'-triphosphate, Mg(2+)ATPgammaS, or Mg(2+)ADP. Taken
      together, these studies indicate that the conformation of the so-called "T-loop,"
      delineated by Lys-155 to Gln-165, is highly sensitive to the chemical identity of
      the nucleotide situated in the binding pocket. This sensitivity to nucleotide
      identity is in sharp contrast to that observed for the "P-loop"-containing
      enzymes, in which the conformation of the binding motif is virtually unchanged in
      the presence or absence of nucleotides.

PMID- 11953436
TI  - Mutational analysis of human thioredoxin reductase 1. Effects on p53-mediated
      gene expression and interferon and retinoic acid-induced cell death.
AB  - The interferon (IFN)-beta and all-trans-retinoic acid combination suppresses
      tumor growth by inducing apoptosis in several tumor cell lines. A genetic
      technique permitted the isolation of human thioredoxin reductase (TR) as a
      critical regulator of IFN/all-trans-retinoic acid-induced cell death. Our recent
      studies have shown that TR1:thioredoxin 1-regulated cell death is effected in
      part through the activation of p53-dependent responses. To understand its death
      regulatory function, we have performed a mutational analysis of TR. Human TR1 has
      three major structural domains, the FAD binding domain, the NADPH binding domain,
      and an interface domain (ID). Here, we show that the deletion of the C-terminal
      interface domain results in a constitutive activation of TR-dependent death
      responses and promotes p53-dependent gene expression. TR mutant without the ID
      still retains its dependence on thioredoxin for promoting these responses. Thus,
      our data suggest that TR-ID acts as a regulatory domain.

PMID- 11953437
TI  - Posttranscriptional regulation of the RAD5 DNA repair gene by the Dun1 kinase and
      the Pan2-Pan3 poly(A)-nuclease complex contributes to survival of replication
      blocks.
AB  - The yeast Dun1 kinase has complex checkpoint functions including DNA damage
      dependent cell cycle arrest in G(2)/M, transcriptional induction of repair genes,
      and regulation of postreplicative DNA repair pathways. Here we report that the
      Dun1 forkhead-associated domain interacts with the Pan3 subunit of the poly(A)
      nuclease complex and that dun1pan2 and dun1pan3 double mutants are dramatically
      hypersensitive to replicational stress. This phenotype was independent of the
      function of Dun1 in regulating deoxyribonucleotide levels as it was also observed
      in strains lacking the ribonucleotide reductase inhibitor Sml1. dun1pan2 mutants
      initially arrested normally in response to replication blocks but died in the
      presence of persistent replication blocks with considerably delayed kinetics
      compared with mutants lacking the Rad53 kinase, indicating that the double
      mutation does not compromise the intra-S phase checkpoint. Interestingly, the
      RAD5 gene involved in error-free postreplication repair pathways was specifically
      up-regulated in dun1pan2 double mutants. Moreover, inducible overexpression of
      RAD5 mimicked the double mutant phenotype by hypersensitizing dun1 mutants to
      replication blocks. The data indicate that Dun1 and Pan2-Pan3 cooperate to
      regulate the stoichiometry and thereby the activity of postreplication repair
      complexes, suggesting that posttranscriptional mechanisms complement the
      transcriptional response in the regulation of gene expression by checkpoint
      signaling pathways in Saccharomyces cerevisiae.

PMID- 11953438
TI  - Isocitrate binding at two functionally distinct sites in yeast NAD+-specific
      isocitrate dehydrogenase.
AB  - Yeast NAD(+)-specific isocitrate dehydrogenase (IDH) is an octamer containing two
      types of homologous subunits. Ligand-binding analyses were conducted to examine
      effects of residue changes in putative catalytic and regulatory isocitrate
      binding sites respectively contained in IDH2 and IDH1 subunits. Replacement of
      homologous serine residues in either subunit site, S98A in IDH2 or S92A in IDH1,
      was found to reduce by half the total number of holoenzyme isocitrate-binding
      sites, confirming a correlation between detrimental effects on isocitrate binding
      and respective kinetic defects in catalysis and allosteric activation by AMP.
      Replacement of both serine residues eliminates isocitrate binding and measurable
      catalytic activity. The putative isocitrate-binding sites of IDH1 and IDH2
      contain five identical and four nonidentical residues. Reciprocal replacement of
      the four nonidentical residues in either or both subunits (A108R, F136Y, T241D,
      and N245D in IDH1 and/or R114A, Y142F, D248T, and D252N in IDH2) was found to be
      permissive for isocitrate binding. This provides further evidence for two types
      of binding sites in IDH, although the authentic residues have been shown to be
      necessary for normal kinetic contributions. Finally, the mutant enzymes with
      residue replacements in the IDH1 site were found to be unable to bind AMP,
      suggesting that allosteric activation is dependent both upon binding of
      isocitrate at the IDH1 site and upon the changes in the enzyme normally elicited
      by this binding.

PMID- 11953439
TI  - YEAF1/RYBP and YAF-2 are functionally distinct members of a cofactor family for
      the YY1 and E4TF1/hGABP transcription factors.
AB  - The transcription factor hGABP/E4TF1 is a heterotetrameric complex composed of
      two DNA-binding subunits (hGABP alpha/E4TF1-60) and two transactivating subunits
      (hGABP beta/E4TF1-53). In order to understand the molecular mechanism of
      transcriptional regulation by hGABP, we searched for proteins that interact with
      the non-DNA-binding subunit, hGABP beta, using yeast two-hybrid screening. We
      identified a human cDNA encoding a protein related to YAF-2 (YY1-associated
      factor 2), which was previously isolated as an interacting partner of the Ying
      Yang-1 (YY1) transcription factor. Reflecting this similarity, both YAF-2 and
      this novel protein (named YEAF1 for YY1- and E4TF1/hGABP-associated factor-1)
      interacted with hGABP beta and YY1 in vitro and in vivo, indicating that YEAF1
      and YAF-2 constitute a cofactor family for these two structurally distinct
      transcription factors. By using yeast three-hybrid assay, we demonstrated that
      hGABP beta and YY1 formed a complex only in the presence of YEAF1, indicating
      that YEAF1 is a bridging factor of these two transcription factors. These
      cofactors are functionally different in that YAF-2 positively regulates the
      transcriptional activity of hGABP but YEAF1 negatively regulates this activity.
      Also, YAF-2 mRNA is highly expressed in skeletal muscle, whereas YEAF1 mRNA is
      highly expressed in placenta. We speculate that the transcriptional activity of
      hGABP is in part regulated by the expression levels of these tissue-specific
      cofactors. These results provide a novel mechanism of transcriptional regulation
      by functionally distinct cofactor family members.

PMID- 11953440
TI  - The human organic cation transporter (hOCT2) recognizes the degree of substrate
      ionization.
AB  - The organic cation transporter, OCT2, plays a role in renal secretion of a broad
      array of weak bases. To determine whether the degree of ionization of these
      compounds plays a role in their interaction with OCT2, we examined the influence
      of external pH values on the activity of the human ortholog of OCT2, as expressed
      in Chinese hamster ovary-K1 cells. Importantly, changing the pH value from 7.0 to
      8.0 had no effect on the rate of transport of the fixed cations,
      tetraethylammonium and 1-methyl-4-phenylpyridinium, i.e. the pH value did not
      have an effect upon the transporter itself. Cimetidine (pK(a) 6.92), a
      competitive inhibitor of hOCT2, displayed a 3.5-fold increase in IC(50) as pH
      values increased from 7 to 8. hOCT2-mediated cimetidine transport decreased over
      this pH range, the consequence of an increase in K(t) and decrease in J(max) at
      the higher pH value. The weak bases trimethoprim and 4-phenylpyridine showed a
      similar pattern of pH-sensitive interaction with hOCT2. The non-ionizable sterol,
      corticosterone, also inhibited hOCT2 activity, although it was neither
      competitive in nature nor was it sensitive to pH in the manner observed with weak
      bases. We conclude that the degree of ionization plays a critical role in binding
      of substrate to organic cation transporters.

PMID- 11953441
TI  - Transcriptional regulation of a contractile gene by mechanical forces applied
      through integrins in osteoblasts.
AB  - We examined mechanotranscriptional regulation of the contractile gene, alpha
      smooth muscle actin (SMA), in osteoblastic cells. Tensile forces were applied
      through collagen-coated magnetite beads to ROS17/2.8 cells. These cells were
      desmin-, vimentin+ and expressed low levels of SMA. After force application (480
      piconewton/cell), SMA protein and mRNA were increased but beta-actin was
      unchanged. Beads coated with bovine serum albumin or poly-L-lysine produced no
      change of SMA. In cells transiently transfected with plasmids containing the SMA
      promoter fused to beta-galactosidase or green fluorescent protein coding
      sequences, SMA promoter activity was increased by approximately 60% after 4 h of
      force, whereas control (Rous sarcoma virus) promoter activity was unaffected.
      Transfections with beta-galactosidase or green fluorescent protein reporter
      constructs showed that force-loaded cells exhibited higher beta-galactosidase
      activity than cells without force. Cytochalasin D and latrunculin B inhibited
      force-induced increases of SMA promoter activity. Deletion analyses showed that
      SMA promoter activity was increased approximately 70% after force with a minimal
      construct containing 155 bp upstream of the translation start site. The force
      effect on the SMA promoter was abrogated in cells transfected with CArG-B box
      mutants. Gel mobility shift analyses of nuclear extracts showed strong binding to
      the CArG-B motif after force. We conclude that the CArG-B box is a force
      responsive element in the SMA promoter.

PMID- 11953442
TI  - Genome-wide profiling of promoter recognition by the two-component response
      regulator CpxR-P in Escherichia coli.
AB  - In Escherichia coli, the two-component Cpx system comprising the CpxA sensor
      kinase and the CpxR response regulator modulates gene expression in response to a
      variety of stresses including membrane-protein damage, starvation, and high
      osmolarity. To date, the few known CpxR-P target operons were mostly identified
      by genetic screens. To facilitate the discovery of all target operons, we derived
      a 15-bp weighted matrix for CpxR-P recognition that takes into account the
      relative base frequency at each nucleotide position. This matrix essentially
      consists of two tandem 5'-GTAAA-3' motifs separated by a 5-bp linker. All of the
      15-bp stretches on both strands of the E. coli MG1655 genome were then scored for
      their degree of matching with the matrix and classified in statistical deviation
      groups. The effectiveness of this screening is indicated by the identification of
      eight new target operons (ung, ompC, psd, mviA, aroK, rpoErseABC, secA, and aer)
      among eleven candidates tested. Moreover, the matrix score correlates with the
      likelihood that a site is a true target and with the relative site affinity for
      CpxR-P in vitro. Our data indicate that some 100 operons are under direct CpxR-P
      control and that the signal transduction pathway interacts with several other
      control circuits in manners hitherto unanticipated.

PMID- 11953443
TI  - A reagent for the detection of reducing sugars. 1908.

PMID- 11953444
TI  - Promotion of neuronal cell adhesion by members of the IgLON family occurs in the
      absence of either support or modification of neurite outgrowth.
AB  - The IgLONs are a family of glycosyl phosphatidyl inositol-linked cell adhesion
      molecules which are thought to modify neurite outgrowth and may play a role in
      cell-cell recognition. The family consists of LAMP, OBCAM, neurotrimin/CEPU-1 and
      neurotractin/kilon. In this paper we report the effect of recombinant LAMP, CEPU
      1 and OBCAM, and transfected cell lines expressing these molecules, on the
      adhesion and outgrowth of dorsal root ganglion (DRG) and sympathetic neurones.
      CHO cells transfected with cDNA for CEPU-1 adhered to a recombinant CEPU-1-Fc
      substrate. However, DRG or sympathetic neurones only adhered to CEPU-1-Fc when
      presented on protein A. Although DRG and sympathetic neurones express IgLONs on
      their surface, both types of neurones exhibited differential adhesion to CEPU-1
      Fc, LAMP-Fc and OBCAM-Fc. Neither DRG nor sympathetic neurones extended neurites
      on a protein A/IgLON-Fc substrate and overexpression of CEPU-1-GFP in DRG
      neurones also failed to stimulate neurite outgrowth on an IgLON-Fc substrate. DRG
      neurones adhered to and extended neurites equally on transfected and non
      transfected cell lines and the recombinant proteins did not modulate the
      outgrowth of neurones on laminin. In contrast to previous reports we suggest that
      IgLONs may not have a primary role in axon guidance but may be more important for
      cell-cell adhesion and recognition.

PMID- 11953446
TI  - Effect of depleting vesicular and cytoplasmic dopamine on
      methylenedioxymethamphetamine neurotoxicity.
AB  - The mechanism by which 3,4-methylenedioxymethamphetamine (MDMA) produces
      serotonin (5-HT) neurotoxicity is unknown but considerable evidence suggests that
      endogenous brain dopamine (DA) is involved. However, it has recently become
      apparent that some of the data implicating brain DA in MDMA neurotoxicity may be
      confounded by drug effects on thermoregulation. The purpose of the present
      studies was to examine the role of DA in MDMA neurotoxicity, while controlling
      for possible confounding effects of drug- induced changes in core temperature.
      Rats were treated with reserpine, alone and in combination with alpha-methyl-p 
      tyrosine (AMPT), to deplete vesicular and cytoplasmic stores of DA. When drug
      induced hypothermia was averted (by raising ambient temperature), the 5-HT
      neuroprotective effects of reserpine and AMPT were no longer apparent. The lack
      of neuroprotection by AMPT and reserpine, alone and in combination, in studies
      that control for the effects of these drugs on core temperature, suggests that DA
      per se is not essential for the expression of MDMA-induced 5-HT neurotoxicity.

PMID- 11953445
TI  - Non-homologous DNA end joining in the mature rat brain.
AB  - Recent evidence suggests that DNA double strand breaks (DSBs) are introduced in
      neurons during the course of normal development, and that repair of such DSBs is
      essential for neuronal survival. Here we describe a non-homologous DNA end
      joining (NHEJ) system in the adult rat brain that may be used to repair DNA DSBs.
      In the brain NHEJ system, blunt DNA ends are joined with lower efficiency than
      cohesive or non-matching protruding ends. Moreover, brain NHEJ is blocked by DNA
      ligase inhibitors or by dATP and can occur in the presence or absence of
      exogenously added ATP. Comparison of NHEJ activities in several tissues showed
      that brain and testis share similar mechanisms for DNA end joining, whereas the
      activity in thymus seems to utilize different mechanisms than in the nervous
      system. The developmental profile of brain NHEJ showed increasing levels of
      activity after birth, peaking at postnatal day 12 and then gradually decreasing
      along with age. Brain distribution analysis in adult animals showed that NHEJ
      activity is differentially distributed among different regions. We suggest that
      the DNA NHEJ system may be utilized in the postnatal brain for the repair of DNA
      double strand breaks introduced within the genome in the postnatal brain.

PMID- 11953447
TI  - Differential expression and localization of calmodulin-dependent
      phosphodiesterase genes during ontogenesis of chick dorsal root ganglion.
AB  - The level and characteristics of 3'-5'-cyclic nucleotide phosphodiesterase (PDE)
      activity in chick dorsal root ganglion (DRG) extracts of 5-day posthatching
      chicken (P5) and E10 and E18 embryos were studied. At all stages, PDE activity is
      stimulated by calcium and calmodulin. A 5-fold increase in basal cAMP and cGMP
      PDE activity is evident from E10 to E18, while from E18 to P5 basal PDE activity
      remains constant. Ion exchange chromatography elution profile indicates that PDE1
      isoforms represent the bulk of the PDE activity present. Inhibition studies were
      performed in order to distinguish the activity due to PDE1A, B and C. Western
      blot analysis using anti-mammalian PDE1A, B and C specific antibodies was also
      performed. Densitometric analysis of the stained bands reveals that PDE1B and
      PDE1C display a prominent increase between day 10 and day 18 of development
      (eight- and 3.6 fold, respectively) while a more limited increase (1.6- and 1.5
      fold) is observed between E18 and P5; on the other hand PDE1A shows continuously
      increasing levels throughout development. Immunohistochemical analysis was
      performed with isoform specific antibodies used for western blot analysis. PDE1A
      immunoreactivity is found in the cytoplasm and fibers of several neurons
      differing in size and distributed throughout the ganglion. PDE1B staining is
      evident on all neurons, however, fibers appear very faintly labelled. All neurons
      appear stained by PDE1C antibody, although the intensity of immunostaining is
      always heterogeneous in different neuronal populations: no staining was evident
      on fibers or in non-neural cells. The distinct spatial and temporal expression
      patterns of PDE1 isoforms may indicate their different physiological roles in
      developing and mature chick DRG.

PMID- 11953448
TI  - Interaction between metabotropic glutamate receptor 7 and alpha tubulin.
AB  - Metabotropic glutamate receptors (mGluRs) mediate a variety of responses to
      glutamate in the central nervous system. A primary role for group-III mGluRs is
      to inhibit neurotransmitter release from presynaptic terminals, but the molecular
      mechanisms that regulate presynaptic trafficking and activity of group-III mGluRs
      are not well understood. Here, we describe the interaction of mGluR7, a group-III
      mGluR and presynaptic autoreceptor, with the cytoskeletal protein, alpha tubulin.
      The mGluR7 carboxy terminal (CT) region was expressed as a GST fusion protein and
      incubated with rat brain extract to purify potential mGluR7-interacting proteins.
      These studies yielded a single prominent mGluR7 CT-associated protein of 55 kDa,
      which subsequent microsequencing analysis revealed to be alpha tubulin.
      Coimmunoprecipitation assays confirmed that full-length mGluR7 and alpha tubulin
      interact in rat brain as well as in BHK cells stably expressing mGluR7a, a splice
      variant of mGluR7. In addition, protein overlay experiments showed that the CT
      domain of mGluR7a binds specifically to purified tubulin and calmodulin, but not
      to bovine serum albumin. Further pull-down studies revealed that another splice
      variant mGluR7b also interacts with alpha tubulin, indicating that the binding
      region is not localized to the splice-variant regions of either mGluR7a (900-915)
      or mGluR7b (900-923). Indeed, deletion mutagenesis experiments revealed that the
      alpha tubulin-binding site is located within amino acids 873-892 of the mGluR7 CT
      domain, a region known to be important for regulation of mGluR7 trafficking.
      Interestingly, activation of mGluR7a in cells results in an immediate and
      significant decrease in alpha tubulin binding. These data suggest that the
      mGluR7/alpha tubulin interaction may provide a mechanism to control access of the
      CT domain to regulatory molecules, or alternatively, that this interaction may
      lead to morphological changes in the presynaptic membrane in response to receptor
      activation.

PMID- 11953449
TI  - Interleukin-1beta-induced substance P release from rat cultured primary afferent
      neurons driven by two phospholipase A2 enzymes: secretory type IIA and cytosolic
      type IV.
AB  - We previously described that recombinant interleukin-1beta (IL-1beta) induced the
      significant release of substance P (SP) via a cyclooxygenase (COX) pathway in
      primary cultured rat dorsal root ganglion (DRG) cells. In the present study, we
      examined the involvement of two types of phospholipase A2 (PLA2) enzymes, which
      lie upstream of COX in the prostanoid-generating pathway, in the IL-1beta-induced
      release of SP from DRG cells. The expression of type IIA secretory PLA2 (sPLA2 
      IIA) mRNA was undetectable by ribonuclease protection assay in non-treated DRG
      cells, while in DRG cells incubated with 1 ng/mL of IL-1beta, the expression was
      induced in a time-dependent manner. On the other hand, type IV cytosolic PLA2
      (cPLA2 ) mRNA was constitutively expressed in the non-treated DRG cells, and
      treatment with 1 ng/mL of IL-1beta for 3 h significantly increased the levels of
      cPLA2 mRNA. The IL-1beta-induced SP release was significantly inhibited by the
      sPLA2 inhibitor, thioetheramide phosphorylcholine (TEA-PC), and the cPLA2
      inhibitor, arachidonyl trifluoromethyl ketone (AACOCF3 ). Furthermore AACOCF3
      suppressed the induction of sPLA2 -IIA mRNA expression induced by IL-1beta. These
      observations suggested that two types of PLA2, sPLA2 -IIA and cPLA2, were
      involved in the IL-1beta-induced release of SP from DRG cells, and that the
      functional cross-talk between the two enzymes might help to control their
      activity in the prostanoid-generating system in DRG cells. These events might be
      key steps in the inflammation-induced hyperactivity in primary afferent neurons
      of spinal cord.

PMID- 11953451
TI  - Dbeta3, an atypical nicotinic acetylcholine receptor subunit from Drosophila :
      molecular cloning, heterologous expression and coassembly.
AB  - Insect nicotinic acetylcholine receptors (nAChRs) play a central role in
      mediating neuronal synaptic transmission and are the target sites for the
      increasingly important group of neonicotinoid insecticides. Six nicotinic
      acetylcholine receptor (nAChR) subunits (four alpha-type and two beta-type) have
      been cloned previously from the model insect species Drosophila melanogaster.
      Despite extensive efforts, it has not been possible to generate functional
      recombinant nAChRs by heterologous expression of any combination of these six
      subunits. It has, however, been possible to express functional hybrid receptors
      when Drosophila alpha subunits are co-expressed with vertebrate beta subunits.
      This has led to the assumption that successful heterologous expression might
      require an, as yet, uncloned beta-type insect subunit. Examination of the
      recently completed Drosophila genomic sequence data has identified a novel
      putative nAChR beta-type subunit. Here we report the molecular cloning,
      heterologous expression and characterization of this putative Drosophila nAChR
      subunit (Dbeta3). Phylogenetic comparisons with other ligand-gated ion channel
      subunit sequences support its classification as a nAChR subunit but show it to be
      a distantly related member of this neurotransmitter receptor subunit family.
      Evidence that the Dbeta3 subunit is able to coassemble with other Drosophila
      nAChR subunits and contribute to recombinant nAChRs has been obtained by both
      radioligand binding and coimmunoprecipitation studies in transfected Drosophila
      S2 cells.

PMID- 11953450
TI  - N -Glycans on the receptor for advanced glycation end products influence
      amphoterin binding and neurite outgrowth.
AB  - In this study we show that embryonic neurite growth-promoting protein amphoterin
      binds to carboxylated N -glycans previously identified on mammalian endothelial
      cells. Since amphoterin is a ligand for the receptor for advanced glycation end
      products (RAGE), and the ligand-binding V-domain of the receptor contains two
      potential N -glycosylation sites, we hypothesized that N -glycans on RAGE may
      mediate its interactions with amphoterin. In support of this, anti-carboxylate
      antibody mAbGB3.1 immunoprecipitates bovine RAGE, and PNGase F treatment reduces
      its molecular mass by 4.5 kDa, suggesting that the native receptor is a
      glycoprotein. The binding potential of amphoterin to RAGE decreases significantly
      in presence of soluble carboxylated glycans or when the receptor is
      deglycosylated. Oligosaccharide analysis shows that RAGE contains complex type
      anionic N -glycans with non-sialic acid carboxylate groups, but not the HNK-1 (3
      sulfoglucuronyl beta1-3 galactoside) epitope. Consistent with the functional
      localization of RAGE and amphoterin at the leading edges of developing neurons,
      mAbGB3.1 stains axons and growth cones of mouse embryonic cortical neurons, and
      inhibits neurite outgrowth on amphoterin matrix. The carboxylated glycans
      themselves promote neurite outgrowth in embryonic neurons and RAGE-transfected
      neuroblastoma cells. This outgrowth requires full-length, signalling-competent
      RAGE, as cells expressing cytoplasmic domain-deleted RAGE are unresponsive. These
      results indicate that carboxylated N -glycans on RAGE play an important
      functional role in amphoterin-RAGE-mediated signalling.

PMID- 11953452
TI  - ELISA analysis of beta-secretase cleavage of the Swedish amyloid precursor
      protein in the secretory and endocytic pathways.
AB  - Limiting beta amyloid (Abeta) production could become an important therapeutic
      target in Alzheimer's disease (AD). Abeta is derived by the sequential cleavage
      of amyloid precursor protein (APP) by beta- and gamma-secretases. A double
      missense mutation in APP found in a Swedish pedigree (APPsw) elevates Abeta40 and
      Abeta42 production. Abeta production and, therefore, beta-secretase cleavage of
      APPsw reportedly occur in the endoplasmic reticulum (ER), Golgi and endocytic
      compartments. However, the relative contribution of beta-secretase cleavage
      occurring in each compartment has not been determined. Experiments described here
      use a novel ELISA to measure the beta-cleaved product, APPswbeta. Using this
      ELISA, we provide new information regarding the relative amount of beta-secretase
      cleavage of APPsw that occurs in secretory and endocytic pathways. Using a
      dilysine retrieval motif to retain APPsw in the ER, we discovered that less than
      15% of the beta-secretase cleavage was still detected. Experiments utilizing
      endocytosis-impaired mutants of APPsw revealed that little or no beta-secretase
      cleavage of APPsw appears to take place through endocytosis. Surprisingly,
      deletion of the entire cytoplasmic tail increased both APPswbeta and Abeta
      secretion, suggesting that protein interactions with this region normally impede
      beta-secretase cleavage. These results suggest that APPsw is cleaved by beta
      secretase late in the secretory pathway.

PMID- 11953453
TI  - Decreased expression of glutamate transporters in genetic absence epilepsy rats
      before seizure occurrence.
AB  - In absence epilepsy, epileptogenic processes are suspected of involving an
      imbalance between GABAergic inhibition and glutamatergic excitation. Here, we
      describe alteration of the expression of glutamate transporters in rats with
      genetic absence (the Genetic Absence Epilepsy Rats from Strasbourg: GAERS). In
      these rats, epileptic discharges, recorded in the thalamo-cortical network,
      appear around 40 days after birth. In adult rats no alteration of the protein
      expression of the glutamate transporters was observed. In 30-day-old GAERS
      protein levels (quantified by western blot) were lower in the cortex by 21% and
      35% for the glial transporters GLT1 and GLAST, respectively, and by 32% for the
      neuronal transporter EAAC1 in the thalamus compared to control rats. In addition,
      the expression and activity of GLAST were decreased by 50% in newborn GAERS
      cortical astrocytes grown in primary culture. The lack of modification of the
      protein levels of glutamatergic transporters in adult epileptic GAERS, in spite
      of mRNA variations (quantified by RT-PCR), suggests that they are not involved in
      the pathogeny of spike-and-wave discharges. In contrast, the alteration of
      glutamate transporter expression, observed before the establishment of epileptic
      discharges, could reflect an abnormal maturation of the glutamatergic neurone
      glia circuitry.

PMID- 11953454
TI  - Activation of caspase-3 alone is insufficient for apoptotic morphological changes
      in human neuroblastoma cells.
AB  - Activated caspase-3 is considered an important enzyme in the cell death pathway.
      To study the specific role of caspase-3 activation in neuronal cells, we
      generated a stable tetracycline-regulated SK-N-MC neuroblastoma cell line, which
      expressed a highly efficient self-activating chimeric caspase-3, consisting of
      the caspase-1 prodomain fused to the caspase-3 catalytic domain. Under expression
      inducing conditions, we observed a time-dependent increase of processed caspase-3
      by immunostaining for the active form of the enzyme, intracellular caspase-3
      enzyme activity, as well as poly(ADP-ribose) polymerase (PARP) cleavage. Induced
      expression of the caspase fusion protein showed predominantly caspase-3 activity
      without any apoptotic morphological changes. In contrast, staurosporine treatment
      of the same cells resulted in activation of multiple caspases and profound
      apoptotic morphology. Our work provides evidence that auto-activation of caspase
      3 can be efficiently achieved with a longer prodomain and that neuronal cell
      apoptosis may require another caspase or activation of multiple caspase enzymes.

PMID- 11953455
TI  - FKHRL1 and its homologs are new targets of nerve growth factor Trk receptor
      signaling.
AB  - We report that the Forkhead family of transcription factors, FKHRL1, FKHR and AFX
      are novel components of neurotrophin receptor signaling. NGF rapidly induced the
      phosphorylation of FKHRL1 in PC12 cells. This effect is mediated by high-affinity
      TrkA receptor as nerve growth factor (NGF) induced the phosphorylation of FKHRL1
      only in TrkA expressing cells and not p75-expressing cells. Additional
      experiments with various kinase inhibitors, the transient expression of
      constitutively active and dominant-negative Akt, and in vitro kinase assay
      revealed that phosphatidylinositol-3 (PtdIns3)/Akt kinase mediated the actions of
      NGF. Similar data were obtained for brain-derived neurotrophic factor (BDNF),
      neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) in primary cortical cultured
      neurons. These findings demonstrate for the first time that the phosphorylation
      of the Forkhead family of transcription factors can be modulated by neurotrophins
      via Trk receptors and PtdIns3K/Akt kinase (but not MAP or S6p70 kinases) in
      neuronal and non-neuronal cells. Moreover, survival assays with the PtdIns3
      kinase inhibitor LY294002, active and dominant-negative forms of Akt indicate
      that the phosphorylation of FKHRL1 plays a role in neurotrophins-mediated cell
      survival.

PMID- 11953456
TI  - Contribution of Ca2+ calmodulin-dependent protein kinase II and mitogen-activated
      protein kinase kinase to neural activity-induced neurite outgrowth and survival
      of cerebellar granule cells.
AB  - In this report we describe our studies on intracellular signals that mediate
      neurite outgrowth and long-term survival of cerebellar granule cells. The effect
      of voltage-gated calcium channel activation on neurite complexity was evaluated
      in cultured cerebellar granule cells grown for 48 h at low density; the parameter
      measured was the fractal dimension of the cell. We explored the contribution of
      two intracellular pathways, Ca2+ calmodulin-dependent protein kinase II and
      mitogen-activated protein kinase kinase (MEK1), to the effects of high [K+ ]e
      under serum-free conditions. We found that 25 mm KCl (25K) induced an increase in
      calcium influx through L subtype channels. In neurones grown for 24-48 h under
      low-density conditions, the activation of these channels induced neurite
      outgrowth through the activation of Ca2+ calmodulin-dependent protein kinase II.
      This also produced an increase in long-term neuronal survival with a partial
      contribution from the MEK1 pathway. We also found that the addition of 25K
      increased the levels of the phosphorylated forms of Ca2+ calmodulin-dependent
      protein kinase II and of the extracellular signal-regulated kinases 1 and 2.
      Neuronal survival under resting conditions is supported by the MEK1 pathway. We
      conclude that intracellular calcium oscillations can triggered different
      biological effects depending on the stage of maturation of the neuronal
      phenotype. Ca2+ calmodulin-dependent protein kinase II activation determines the
      growth of neurites and the development of neuronal complexity.

PMID- 11953457
TI  - Direct evidence that release-stimulating alpha7* nicotinic cholinergic receptors
      are localized on human and rat brain glutamatergic axon terminals.
AB  - The existence on glutamatergic nerve endings of nicotinic acetylcholine receptors
      (nAChRs) mediating enhancement of glutamate release has often been suggested but
      not demonstrated directly. Here, we study the effects of nAChR agonists on [3 H]
      d-aspartate ([3 H]-d-ASP) release from synaptosomes superfused in conditions
      known to prevent indirect effects. Nicotinic receptor agonists, while unable to
      modify the basal [3 H]-d-ASP release from human neocortex or rat striatal
      synaptosomes, enhanced the Ca2+ -dependent exocytotic release evoked by K+ (12
      mm) depolarization. Their rank order of potency were anatoxin-a > epibatidine >
      nicotine > ACh (+ atropine). The anatoxin-a effect, both in human and rat
      synaptosomes, was antagonized by mecamylamine, alpha-bungarotoxin or
      methyllycaconitine. The basal release of [3 H]ACh from human cortical
      synaptosomes was increased by (-)-nicotine (EC50 = 1.16 +/- 0.33 microm) or by
      ACh plus atropine (EC50 = 2.0 +/- 0.04 microm). The effect of ACh plus atropine
      was insensitive to alpha-bungarotoxin, methyllycaconitine or alpha-conotoxin MII,
      whereas it was totally antagonized by mecamylamine or dihydro-beta-erythroidine.
      To conclude, glutamatergic axon terminals in human neocortex and in rat striatum
      possess alpha7* nicotinic heteroreceptors mediating enhancement of glutamate
      release. Release-enhancing cholinergic autoreceptors in human neocortex are
      nAChRs with a pharmacological profile compatible with the alpha4beta2 subunit
      combination.

PMID- 11953458
TI  - The disulphide bonds in the catalytic domain of BACE are critical but not
      essential for amyloid precursor protein processing activity.
AB  - beta-Site APP-cleaving enzyme (BACE) initiates the processing of the amyloid
      precursor protein (APP) leading to the generation of beta-amyloid, the main
      component of Alzheimer's disease senile plaques. BACE (Asp2, memapsin 2) is a
      type I transmembrane aspartic protease responsible for the beta-secretase
      cleavage of APP producing a soluble form of the ectodomain (sAPPbeta) and the
      membrane-bound, carboxy-terminal intermediates C99 and C89. BACE maturation
      involves cysteine bridge formation, N -glycosylation and propeptide removal. We
      investigated variants of BACE in which the disulphide bonds of the catalytic
      domain spanning between Cys216/Cys420, Cys278/Cys443 and Cys330/Cys380 were
      removed by mutagenesis. When transfected in cultured cells, these mutants showed
      impaired maturation. Nevertheless, a fraction of mutated protein retained both
      the competence to mature as well as the activity to process APP. For the
      generation of a functional enzyme the conserved Cys330/Cys380 bond was the most
      critical, whereas the two bonds between Cys216/Cys420 and Cys278/Cys443, which
      are typical for the membrane-bound BACE, appeared to be less important.

PMID- 11953459
TI  - Fra-1 substitutes for c-Fos in AP-1-mediated signal transduction in retinal
      apoptosis.
AB  - Lack of the AP-1 member c-Fos protects photoreceptors against light-induced
      apoptosis, a model for retinal degeneration. In mice, light damage increases the
      activity of the transcription factor AP-1, while pharmacological suppression of
      AP-1 prevents apoptosis, suggesting the involvement of pro-apoptotic AP-1 target
      genes. Recently, however, it was shown that photoreceptors expressing Fra-1 in
      place of c-Fos (Fos (Fosl1/Fosl1) ) are apoptosis competent despite the lack of
      transactivation domains in Fra-1. Here, we show that morphological features of
      light-induced apoptosis were indistinguishable in Fos (Fosl1/Fosl1) and wild-type
      mice. Furthermore, light exposure comparably increased AP-1 activity in both
      genotypes. Opposite to wild-type mice, Fra-1, but not c-Fos, was detectable in AP
      1 complexes of Fos (Fosl1/Fosl1) mice. Importantly, AP-1 responsiveness for
      glucocorticoid receptor-mediated inhibition was preserved in Fos (Fosl1/Fosl1)
      mice. Thus, Fra-1 takes over for c-Fos in pro- and anti-apoptotic signal
      transduction. As Fra-1 lacks transactivation domains, AP-1 may not induce, but
      rather suppress genes in retinal light damage.

PMID- 11953460
TI  - Modulation of cannabinoid agonist binding by 5-HT in the rat cerebellum.
AB  - Cross-talk between cannabinoid CB1 and serotonin 5-HT receptors in rat cerebellar
      membranes was investigated using radioligand binding. In competition against the
      CB1 antagonist, [3 H]SR141716A, the agonist, WIN 55,212-2 yielded a biphasic
      isotherm. The majority of binding was to a high-affinity state that was
      significantly reduced by the GTP analogue, Gpp(NH)p. Interestingly, 5-HT enhanced
      the high-affinity binding constant of WIN 55,212-2 while attenuating the
      proportion of high-affinity binding. 5-HT also significantly reduced the
      proportion of high-affinity binding of the cannabinoid agonist, HU 210, but had
      no effect on the agonist, CP 55,940. The effect of 5-HT on WIN 55,212-2 binding
      was inhibited by the 5-HT2 receptor antagonist ritanserin as well as Gpp(NH)p,
      suggesting a dependence on the 5-HT2 receptor and on G protein-receptor
      interactions, respectively. Subsequent [3 H]WIN 55,212-2 dissociation kinetic
      experiments revealed that 5-HT promoted a slower-dissociating species of
      radiolabelled agonist-receptor complex. Our findings support a membrane-delimited
      cross-talk between two G protein-coupled receptors that are co-localized in
      certain cells of the central nervous system. Intriguingly, the cannabinoid
      agonist dependence of the 5-HT modulatory effect suggests that agonist-specific
      conformations of the CB1 receptor may also be important in determining the extent
      of this cross-talk.

PMID- 11953461
TI  - National program for preventing mother-child HIV transmission in Thailand:
      successful implementation and lessons learned.
AB  - OBJECTIVE: To describe the development, components, and initial uptake of
      Thailand's national program for preventing mother-child HIV transmission. DESIGN:
      Historical review, interpretation of experience, national program monitoring.
      SETTING: Public health system, Thailand. PARTICIPANTS: Policymakers, clinicians,
      HIV-infected pregnant women. INTERVENTION: Voluntary counseling and HIV testing
      of pregnant women; short-course zidovudine for HIV-infected women and their
      infants and formula feeding for infants. MAIN OUTCOME MEASURES: Program
      components implemented and program uptake. RESULTS: Research, monitoring and
      evaluation of pilot projects, training, and policy-making provided the
      information, experience, infrastructure, and guidance to develop a program for
      preventing mother-child HIV transmission that was implemented in all Ministry of
      Public Health hospitals in Thailand in 2000. A national system was established to
      monitor program implementation. Monitoring reports were received from 669
      hospitals in 65 provinces for the period October 2000 through July 2001. During
      this period, 93% of 318 721 women who gave birth were tested for HIV; 69% of 3958
      HIV-infected women giving birth received zidovudine; and 86% and 80% of the 3865
      children born to HIV-infected women received zidovudine and infant formula,
      respectively, through the program. CONCLUSIONS: A national program for preventing
      mother-child HIV transmission was successfully implemented in Thailand. Early
      monitoring indicates good program uptake. Lessons learned from implementing this
      program include the importance of paying attention to counseling, communication,
      and training in the program, and using pilot projects and focused monitoring and
      evaluation data to guide the program development, expansion, and improvement.

PMID- 11953462
TI  - Cross-reactive cytotoxic T lymphocytes against a HIV-1 p24 epitope in slow
      progressors with B*57.
AB  - OBJECTIVES: To determine whether CD8 T lymphocytes from HIV-1-infected patients
      expressing B*5701 and B*5703 show broad cross-reactivity against different
      variants of a conserved p24 epitope, which might account for the good prognosis
      of HIV-1-infected individuals with HLA-B*57. DESIGN: B*5701+ and B*5703+ were
      recruited from Nairobi, Kenya and from Oxford, UK. All patients had been HIV
      positive for at least 8 years and could be categorized as slow progressors.
      METHODS: CD8 cytotoxic T cell clones were generated from B*5701+ and B*5703+
      donors and tested for their ability to recognize clade variants of an index p24
      epitope in standard cytolytic assays. Cross-reactive responses in freshly
      isolated peripheral blood mononuclear cells (PBMC) were assessed by interferon
      gamma (IFNgamma) production and tetramer binding. RESULTS: Broad cross-clade
      reactivity for both cytolysis and tetramer binding was observed in CD8 T cell
      clones from patients harbouring the index epitope sequence. Patterns of cross
      reactivity were similar in freshly isolated PBMC but varied between individuals
      in terms of strength and breath of responses generated. One common variant
      induced an unusual response with tetramer binding but often failed to induce
      IFNgamma production, and another was a weak stimulator of both IFNgamma and
      cytolytic activity. CONCLUSION: B*5701+ and B5703+ donors demonstrate broad
      functional cross-reactivity to both common and rare variants of a dominant p24
      epitope, which could be relevant to the association of B*57 alleles with slow
      progression to AIDS.

PMID- 11953463
TI  - Skeletal muscle mitochondrial function and exercise capacity in HIV-infected
      patients with lipodystrophy and elevated p-lactate levels.
AB  - OBJECTIVE: To investigate the skeletal muscle mitochondrial function in HIV
      infected patients with lipodystrophy or elevated p-lactate levels. DESIGN: Eight
      HIV patients treated with highly active antiretroviral therapy, with
      lipodystrophy or elevated p-lactate, and eight healthy controls were exposed to
      incremental exercise until exhaustion. METHODS: Blood samples and gas analysis
      were performed at rest, during exercise and in recovery. Oxygen consumption,
      workload and blood lactate were assessed. Before and immediately after exercise
      muscle biopsies were obtained, in which citrate synthase (CS), hydroxyacyl
      coenzyme A dehydrogenase (HD), glycogen and nucleotides were measured. RESULTS:
      Maximal workload was significantly lower in patients compared with controls [171
      Watt (88-206) versus 235 Watt (118-294) P = 0.05]. A trend towards lower maximal
      oxygen consumption (VO(2max)) was detected in patients [2136 ml/min (1221-2598)
      versus 2985 ml/min (1506-3959) P = 0.11]. Patients had significantly elevated
      levels of blood lactate at rest [1.55 mmol/l (1-2.5) versus 0.8 mmo/l (0.37-1.1)
      P < 0.01), but no significant difference in maximal blood-lactate values was
      found. The decline in blood lactate in the recovery period was similar between
      groups. There was no significant difference in CS, HD, glycogen or nucleotides.
      CONCLUSION: The significantly lower working capacity and the trend towards
      reduced VO(2max) in patients could be caused by mitochondrial dysfunction, but
      may also be caused by impaired physical fitness. The similar levels of
      nucleotides, CS, HD, and glycogen and the normal increase in blood lactate during
      exercise indicates a normal oxidative phosphorylation. No evidence of serious
      damage to skeletal muscle mitochondrial function was found.

PMID- 11953465
TI  - High Epstein-Barr virus (EBV) DNA loads in HIV-infected patients: correlation
      with antiretroviral therapy and quantitative EBV serology.
AB  - OBJECTIVE: To study Epstein-Barr virus (EBV) DNA loads in peripheral blood of HIV
      carriers to determine base-line values and diagnostic relevance of viral load in
      relation to quantitative serology; to compare EBV presence in parallel plasma and
      unfractionated whole blood samples; and to correlate EBV DNA load to HIV, CD4 T
      cell counts and HAART. DESIGN: One-hundred and nine random patients receiving
      highly active antiretroviral therapy (HAART) during 1999 and 99 patients on anti
      HIV monotherapy during 1993-1996 were included. METHODS: EBV DNA load was
      determined by quantitative competitive PCR. EBV serology was determined by
      immunoblot profile and quantitative enzyme-linked immunosorbent assay for
      responses against VCA-p18 and EBNA-1. RESULTS: Twenty-two out of 109 patients
      receiving HAART and 28 out of 99 of patients on anti-HIV monotherapy showed
      elevated EBV DNA loads in whole blood (> 2000 copies/ml), without elevated loads
      in parallel plasma. EBV DNA load distribution did not differ between the two
      groups (P = 0.78) and did not correlate with HIV or CD4 T-cell count. In three
      patients with high EBV DNA loads EBV RNA was virtually absent. Patients with high
      EBV DNA loads (3610-89 400 copies/ml) had higher anti-VCA-p18 IgG levels than
      patients with undetectable EBV DNA (P < 0.0001) but lower anti-EBNA-1 IgG levels
      (P = 0.005). CONCLUSION: Absolute values of EBV DNA load may have poor diagnostic
      value for defining HIV patients at risk for developing EBV-associated disease.
      Elevated EBV DNA loads are cell-associated and are not influenced by HAART.
      Increased anti-p18-VCA and decreased anti-EBNA-1 IgG levels in patients with high
      EBV loads indicate impaired latency control and increased lytic replication
      suggesting disturbed overall immunosurveillance against EBV.

PMID- 11953464
TI  - Supernatants of HIV-infected immune cells affect the barrier function of human HT
      29/B6 intestinal epithelial cells.
AB  - OBJECTIVES: Characterization of the diarrhoea-inducing effect of altered cytokine
      production in HIV infection. METHODS: Monocyte-derived macrophages (MDM) were
      infected with macrophagetropic (SF162) and lymphocytotropic (IIIB) HIV-1 strains
      and cocultured with autologous peripheral blood mononuclear cells (PBMC). After
      24 h the supernatants were collected and tested for their immunoreactive levels
      of cytokines by enzyme-linked immunosorbent assay. The effects of the
      supernatants and the respective recombinant human cytokines on barrier function
      of HT-29/B6 cells were determined. RESULTS: Infection of MDM with HIV-1 SF162 or
      IIIB led to increased production of tumour necrosis factor-alpha (TNFalpha),
      interleukin-1-beta, interferon-alpha and interferon-gamma after cell-cell contact
      with PBMC. Supernatants of infected cells decreased transepithelial resistance
      (R(t)), with higher effects on R(t) in HIV IIIB infection, which was due to
      higher cytokine concentrations. The effect was not due to cytotoxicity (negative
      LDH assay) or epithelial monolayer disruption [zonula occludens protein-1 (ZO-1)
      immunofluorescence staining]. The effect of HIV-1 IIIB coculture supernatants
      could be mimicked by the respective recombinant human cytokines. TNFalpha is an
      effector cytokine, because inhibition of TNFalpha by its soluble receptor
      decreased the effect of the supernatants on transepithelial resistance.
      Conductance scanning indicated the cytokine-induced barrier defect to be due to
      both, induction of epithelial apoptoses and tight junction alterations.
      CONCLUSIONS: Cell-cell interaction of HIV-infected macrophages with PBMC leads to
      a release of cytokines sufficient to alter intestinal epithelial barrier
      function. The main effect was mediated by TNFalpha inducing a leak-flux which may
      contribute to the diarrhoea by HIV per se (HIV-enteropathy).

PMID- 11953466
TI  - Non-cytotoxic inhibition of HIV-1 infection by unstimulated CD8+ T lymphocytes
      from HIV-exposed-uninfected individuals.
AB  - OBJECTIVES: Some individuals remain uninfected despite repeated exposure to HIV-1
      [exposed-uninfected (EU)]. In addition to genetic factors, acquired immune
      responses elicited by repeated exposure to HIV antigens may contribute to
      protection. We investigated the ability of unstimulated CD8+ T lymphocytes from
      EU individuals to inhibit HIV-1 infection. METHODS: Peripheral blood CD8+ T
      lymphocytes from a well-characterized cohort of 16 HIV-1-discordant monogamous
      heterosexual couples were tested for their suppressive activity against HIV-1
      strains displaying different coreceptor usage (R5, X4, X4R5). To evaluate the in
      vivo functional competence of CD8+ T cells, no ex vivo activatory stimuli were
      used prior to cocultivation with infected CD4+ T cells. In some experiments, a
      semi-permeable membrane was used to separate CD4+ and CD8+ T cells. RESULTS:
      Unstimulated CD8+ T cells from all but one of the EU individuals analysed
      effectively inhibited the growth of all HIV-1 strains, regardless of their
      coreceptor usage, with a mean potency similar to that of asymptomatic HIV
      infected patients. The HIV-inhibitory activity persisted for a long time after
      ceasing high-risk sexual behaviour, although a moderate decline was observed
      starting 4 years after the last risk episode. Transwell culture experiments
      showed that soluble factors are involved in CD8-mediated viral suppression,
      although the activity was higher when cell-to-cell contact was allowed.
      CONCLUSIONS: These data demonstrate that CD8+ T cells from EU individuals exert a
      strong, broad-spectrum HIV-suppressive activity, suggesting a role of non
      cytotoxic antiviral mechanisms in resistance to HIV-1 infection.

PMID- 11953467
TI  - Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced
      replication capacity.
AB  - OBJECTIVES: To evaluate protease inhibitor (PI) cross-resistance and reductions
      in replication capacity conferred by amprenavir-selected mutations. METHODS: HIV
      1IIIB variants derived from passage in increasing concentrations of amprenavir
      were studied, as well as 3'Gag/protease recombinants derived from them. These
      strains progressively accumulated mutations at codons 10, 46, 47, 50 and 84 in
      the protease as well as a p1/p6 cleavage site mutation at codon 449 in Gag. Their
      susceptibility (IC50) to various PI and their corresponding replication
      capacities were evaluated by a single-cycle growth assay and compared with
      measures using competitive cultures and p24 antigen production. RESULTS:
      Amprenavir susceptibility decreased with increasing numbers of protease
      mutations. Changes in lopinavir susceptibility paralleled changes in amprenavir
      susceptibility. Certain amprenavir-selected mutants conferred greater than 10
      fold cross-resistance to lopinavir, including PrL10F/M46I/I50V-GagL449F (19-fold)
      and PrL10F/M46I/I47V/I50V-GagL449F (31-fold). Moreover, one isolate with only two
      mutations in the protease (L10F/84V) and GagL449F displayed a 7.7-fold increase
      in lopinavir IC50. Low-level cross-resistance to ritonavir and nelfinavir was
      also observed. The replication capacity of viruses containing either I84V or I50V
      was at least 90% lower than the reference virus in the single-cycle assay. The
      order of relative replication capacity was wild-type > L10F > L10F/I84V >
      L10F/M46I/I50V > L10F/M46I/I47V/I50V. CONCLUSION: These results indicate that
      until more comprehensive genotype-phenotype correlations between amprenavir and
      lopinavir susceptibility are established, phenotypic testing may be preferable to
      genotyping to detect cross-resistance, and should be considered when switching
      patients from a failing amprenavir-containing regimen. This study also provides
      data on the concordance of replication capacity measurements generated using
      rapid single-cycle growth and competition assays.

PMID- 11953469
TI  - Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults.
AB  - OBJECTIVE: Despite the recognition of Cryptococcus neoformans as a major cause of
      meningitis in HIV-infected adults in sub-Saharan Africa, little is known about
      the relative importance of this potentially preventable infection as a cause of
      mortality and suffering in HIV-infected adults in this region. DESIGN: A cohort
      study of 1372 HIV-1-infected adults, enrolled and followed up between October
      1995 and January 1999 at two community clinics in Entebbe, Uganda. METHODS:
      Systematic and standardized assessment of illness episodes to describe
      cryptococcal disease and death rates. RESULTS: Cryptococcal disease was diagnosed
      in 77 individuals (rate 40.4/1000 person-years) and was associated with 17% of
      all deaths (77 out of 444) in the cohort. Risk of infection was strongly
      associated with CD4 T cell counts < 200 x 10(6) cells/l(75 patients) and World
      Health Organization (WHO) clinical stage 3 and 4 (68 patients). Meningism was
      present infrequently on presentation (18%). Clinical findings had limited
      discriminatory diagnostic value. Serum cryptococcal antigen testing was the most
      sensitive and robust diagnostic test. Cryptococcal antigenaemia preceded symptoms
      by a median of 22 days (> 100 days in 11% of patients). Survival following
      diagnosis was poor (median survival 26 days; range 0-138). CONCLUSIONS:
      Cryptococcal infection is an important contributor to mortality and suffering in
      HIV-infected Ugandans. Improvements in access to effective therapy of established
      disease are necessary. In addition, prevention strategies, in particular
      chemoprophylaxis, should be evaluated while awaiting the outcome of initiatives
      to make antiretroviral therapy more widely available.

PMID- 11953470
TI  - Drug resistance at low viraemia in HIV-1-infected patients with antiretroviral
      combination therapy.
AB  - OBJECTIVE: To study the appearance of drug-induced mutations at low viraemia in
      treated HIV-1-infected patients. DESIGN AND METHODS: Fourteen patients, who
      received their first (n = 5), second (n = 7) or third (n = 2) line antiretroviral
      combination therapy, developed a persistent low-grade viraemia after an initial
      decrease of the viral load (VL) to less than 500 copies/ml. The amount of HIV-1
      RNA (n = 71) and reverse transcriptase (RT)/protease sequences (n = 56) were
      determined in longitudinally obtained plasma samples during a mean period of 16.6
      months. RESULTS: In the vast majority (93%) of patients, new primary resistance
      mutations were found in the RT and/or protease genes at virological failure at a
      median VL of 500 and 200 copies/ml, respectively. Drug-experienced patients
      developed mutations at a lower VL than naive patients. In one previously protease
      inhibitor-naive patient, primary RT and protease mutations were detected,
      although the VL was less than 50 copies/ml. A serial accumulation of drug
      resistance mutations was seen despite the VL increase being mostly modest,
      reaching a median of 1450 copies/ml at the end of the study, and the CD4 T cell
      counts continued to increase. One patient still had a VL of 300 copies/ml after
      28 months, despite the presence of the multidrug-resistance Q151M mutation.
      CONCLUSION: Low viraemia after virological treatment failure can select for virus
      with several new drug resistance mutations, despite a concomitant increase in CD4
      T cell counts. This serial accumulation of mutations is likely to exhaust future
      drug options

PMID- 11953468
TI  - Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral
      therapy.
AB  - OBJECTIVES: To describe a severe form of demyelinating HIV-associated
      leukoencephalopathy in AIDS patients failing highly active antiretroviral therapy
      (HAART), its relationship to clinical and neuroimaging findings, and suggest
      hypotheses regarding pathogenesis. DESIGN AND METHODS: AIDS patients who failed
      HAART and displayed severe leukoencephalopathy were included. All cases had
      detailed neuromedical, neuropsychological, neuroimaging and postmortem
      neuropathological examination. Immunocytochemical and PCR analyses were performed
      to determine brain HIV levels and to exclude other viruses. RESULTS: Seven recent
      autopsy cases of leukoencephalopathy in antiretroviral-experienced patients with
      AIDS were identified. Clinically, all were severely immunosuppressed, six (86%)
      had poorly controlled HIV replication despite combination antiretroviral therapy,
      and five (71%) had HIV-associated dementia. Neuropathologically, all seven had
      intense perivascular infiltration by HIV-gp41 immunoreactive
      monocytes/macrophages and lymphocytes, widespread myelin loss, axonal injury,
      microgliosis and astrogliosis. The extent of damage exceeds that described prior
      to the use of HAART. Brain tissue demonstrated high levels of HIV RNA but
      evidence of other pathogens, such as JC virus, Epstein-Barr virus,
      cytomegalovirus, human herpes virus type-8, and herpes simplex virus types 1 and
      2, was absent. Comparison of the stages of pathology suggests a temporal sequence
      of events. In this model, white matter damage begins with perivascular
      infiltration by HIV-infected monocytes, which may occur as a consequence of
      antiretroviral-associated immune restoration. Intense infiltration by immune
      cells injures brain endothelial cells and is followed by myelin loss, axonal
      damage, and finally, astrogliosis. CONCLUSIONS: Taken together, our findings
      provide evidence for the emergence of a severe form of HIV-associated
      leukoencephalopathy. This condition warrants further study and increased
      vigilance among those who provide care for HIV-infected individuals.

PMID- 11953472
TI  - Intermittent use of triple-combination therapy is predictive of mortality at
      baseline and after 1 year of follow-up.
AB  - OBJECTIVE: To characterize the impact of intermittent use of triple drug
      antiretroviral therapy on survival. DESIGN, SETTING AND PARTICIPANTS: Population
      based analysis of 1282 antiretroviral therapy naive HIV-positive individuals aged
      18 years and older in British Columbia who started triple-combination therapy
      between August 1996 and December 1999. Therapy use was estimated by dividing the
      number of months of medications dispensed by the number of months of follow-up.
      Intermittent therapy was defined as the participant having obtained less than 75%
      of their medication in the first 12 months. MAIN OUTCOME MEASURE: Cumulative all
      cause mortality rates from the start of triple drug antiretroviral therapy to 30
      September 2000. RESULTS: As of 30 September 2000, 106 subjects had died.
      Cumulative mortality was 3.9% (+/- 0.5%) at 12 months. In a multivariate model,
      after controlling for other variables that were significant in the univariate
      analyses each 100 cell decrement in baseline CD4 cell count and the intermittent
      use of antiretroviral drugs were associated with increased mortality with risk
      ratios of 1.31 [95% confidence interval (CI), 1.16-1.49; P < 0.001] and 2.90 (95%
      CI, 1.93-4.36; P < 0.001), respectively. In order to control for downward drift,
      intermittent use of therapy was measured over the first year whereas other
      factors were measured at the end of year 1. After adjusting for all other
      factors, those participants who used antiretroviral drugs intermittently were
      2.97 times (95% CI, 1.33-6.62; P = 0.008) more likely to die. CONCLUSION: Our
      study demonstrates that even after adjusting for other prognostic factors
      intermittent use of antiretroviral therapy was associated with increased
      mortality.

PMID- 11953471
TI  - Aseptic meningitis and optic neuritis preceding varicella-zoster progressive
      outer retinal necrosis in a patient with AIDS.
AB  - Varicella-Zoster Virus (VZV) is the second most common ocular pathogen in
      patients with HIV infection. VZV retinitis is estimated to occur in 0.6% of
      patients with HIV infection and may occur in one of two clinical syndromes. The
      first is the acute retinal necrosis syndrome, which also may be seen in
      immunocompetent hosts. The second clinical syndrome occurs in patients with CD4
      cell counts typically < 50 x 10(6)/l and is termed progressive outer retinal
      necrosis. VZV retinitis has been reported to occur simultaneously with other VZV
      central nervous system manifestations such as encephalitis and myelitis in HIV
      infected patients. In addition, VZV retrobulbar optic neuritis heralding VZV
      retinitis has recently been described in HIV-infected patients who had suffered a
      recent episode of dermatomal herpes zoster. Herein we report the case of an HIV
      infected individual who presented with VZV meningitis and retrobulbar optic
      neuritis that preceded the onset of progressive outer retinal necrosis. We also
      review of the literature of seven additional reported cases of retrobulbar optic
      neuritis preceding the onset of VZV retinitis.

PMID- 11953473
TI  - Community study of the relative impact of HIV-1 and HIV-2 on intrathoracic
      tuberculosis.
AB  - BACKGROUND: HIV-1 infection is associated with an increased incidence of and
      mortality from tuberculosis. Few community studies have examined the effect of
      HIV-2 on tuberculosis. METHODS: We investigated the association between HIV-1,
      HIV-2 and active tuberculosis in four districts (population 42 709) in Bissau,
      capital of Guinea-Bissau, with the highest known seroprevalence of HIV-2
      infection in the world. From May 1996 to June 1998, tuberculosis surveillance and
      active case finding among contacts was conducted. Patients were HIV-tested, given
      specific tuberculosis treatment for 8 months and followed regarding mortality.
      Simultaneously, an HIV sero-survey was performed in a random sample of 1748
      permanent residents. RESULTS: During a 25-month period, 366 tuberculosis cases
      were identified. After excluding cases among visitors to the area, and adjusting
      for age, the incidence of tuberculosis was 18.3 times higher (95% CI 12.9-26.0)
      among HIV-1-positive individuals, 13.7 times higher (9.0-20.7) among dually
      infected (HIV-1 and HIV-2), and 3.0 times higher (2.1-4.3) among HIV-2-infected
      compared with HIV-negative individuals. HIV-1 and dually infected tuberculosis
      patients had a higher mortality rate than HIV-negative tuberculosis patients
      [mortality ratio (MR) 2.68; CI 1.11-6.48 and 2.89; CI 1.13-7.39, respectively].
      The survival of HIV-2-positive tuberculosis patients was similar to that of HIV
      negative tuberculosis patients (MR 1.19; CI 0.46-3.06). CONCLUSION: The presence
      of HIV-2 infection increases the incidence of tuberculosis compared with that in
      non-HIV-infected individuals, but does not affect tuberculosis-related mortality
      in the short term. In contrast, the presence of HIV-1 infection, alone or with
      HIV-2, has a several-fold greater impact on both the incidence of and mortality
      from tuberculosis.

PMID- 11953475
TI  - HIV-1 Vpu represents a minor target for cytotoxic T lymphocytes in HIV-1
      infection.
AB  - We have previously shown that Vpu is rarely targeted by HIV-1-specific cytotoxic
      T lymphocytes (CTL). The present report extends these findings and describes the
      characterization of the first CTL epitope within HIV-1 Vpu, identified in an
      individual with long-term non-progressive HIV-1 infection. The epitope was shown
      to be highly conserved among HIV clade B sequences and is restricted by HLA
      A*3303, an HLA allele commonly seen in Asian and west-African populations.

PMID- 11953474
TI  - Prescribing practices in a population-based HIV postexposure prophylaxis program.
AB  - OBJECTIVES: To characterize factors associated with being prescribed triple or
      double postexposure prophylaxis (PEP) against HIV in a population-based program.
      METHODS: Individuals potentially exposed to HIV received a 5 day starter kit of
      either double or triple antiretroviral PEP between April 1999 and November 2000
      and did/did not receive the remaining 23 days PEP. Data were collected through
      dispensation of kits. Logistic regression identified characteristics
      independently associated with being prescribed triple therapy starter kits and
      with any 23 day follow-up. RESULTS: Of 2064 people receiving 5 day PEP [403 (20%)
      triple and 1661 (80%) double], 590 (29%) received 23 day follow-up. Independently
      associated with being prescribed triple therapy starter kits were being male
      [adjusted odds ratio (AOR) 1.38; 95% confidence interval (CI) 1.10-1.74; P =
      0.006), occupational mucocutaneous injuries (AOR 1.70; 95% CI, 1.14-2.55; P =
      0.010), and community needlesticks (AOR 2.04; 95% CI, 1.54-2.69; P < 0.001).
      Independently associated with being prescribed the 23 day follow-up were being
      male (AOR 1.24; 95% CI, 1.00-1.53; P = 0.04), community mucocutaneous incidents
      (AOR 2.83; 95% CI, 1.41-5.70; P = 0.004), community needlesticks (AOR 1.75; 95%
      CI, 1.33-2.29; P < 0.001), and having received triple therapy as the starter kit
      (AOR 2.61; 95% CI, 2.07-3.29; P < 0.001). CONCLUSIONS: Being prescribed triple
      therapy starter PEP was associated with being male and with experiencing an
      occupational mucocutaneous or community needlestick injury. Receiving the
      remaining 23 days PEP was associated with being male, experiencing a community
      mucocutaneous or needlestick injury, and triple therapy as the initial 5 day
      starter PEP.

PMID- 11953476
TI  - CD4 cell count changes in individuals with counts above 500 cells/mm and viral
      loads below 50 copies/ml on antiretroviral therapy.

PMID- 11953477
TI  - Normalization of cytomegalovirus-specific CD4 T cells in HIV-1-infected
      individuals receiving antiretroviral therapy.

PMID- 11953479
TI  - The effect of AIDS on maternal mortality in Malawi and Zimbabwe.

PMID- 11953478
TI  - Efficacy and safety of abacavir plus efavirenz as a salvage regimen in HIV
      infected individuals after 48 weeks.

PMID- 11953480
TI  - Warning: antiretroviral treatment interruption could lead to an increased risk of
      HIV transmission.

PMID- 11953481
TI  - High rate of discontinuations of highly active antiretroviral therapy as a result
      of antiretroviral intolerance in clinical practice: missed opportunities for
      adherence support?

PMID- 11953482
TI  - Switching to zidovudine plus lamivudine plus abacavir maintains viral suppression
      in patients with high viral load before antiretroviral therapy: a retrospective
      clinical cohort analysis.

PMID- 11953483
TI  - Lipodystrophy body-shape changes in a patient undergoing zidovudine monotherapy.

PMID- 11953484
TI  - Human herpesvirus 8 cytoviraemia rebound in a patient with Kaposi's sarcoma after
      a short interruption of efficient antiretroviral therapy.

PMID- 11953485
TI  - Homicide by decubitus ulcers.
AB  - Traditionally, the only penalties for poor treatment of nursing home patients
      have been civil lawsuits against nursing homes and their employees by families,
      or fines and license suspension by government organizations. Recently, government
      agencies have become much more aggressive in citing institutions for the
      development of decubitus ulcers (pressure sores) in their patients. A few
      government institutions have concluded that in some cases, the development of
      ulcers with resultant death is so grievous that there should be criminal
      prosecution of the individuals and/or institutions providing care. A leader in
      this concept has been the State of Hawaii. In November 2000, the State of Hawaii
      convicted an individual of manslaughter in the death of a patient at an adult
      residential care home (a form of nursing home) for permitting the progression of
      decubitus ulcers without seeking medical help, and for not bringing the patient
      back to a physician for treatment of the ulcers.

PMID- 11953486
TI  - Death resulting from ruptured cerebral artery aneurysm: 219 cases.
AB  - To characterize the demographics of ruptured cerebral artery aneurysm as a cause
      of death and to examine the effect of improved diagnostic and therapeutic
      techniques on the incidence of sudden death associated with the condition, the
      authors reviewed 219 autopsies performed at the Dallas County Medical Examiner's
      Office between 1977 and 1997 in which the cause of death was ruptured cerebral
      artery aneurysm. Ruptured cerebral artery aneurysms accounted for 1.5% of 15,033
      natural deaths and 0.4% of all deaths (45,492) followed by autopsy during this
      period. The majority (56%) of cases occurred in females, with Caucasian females
      composing the largest group (38%). Seventy-seven percent of cases occurred in
      individuals between the ages of 31 and 70 years, with the highest concentration
      in the 41- to 50-year decade (29%). The most common location for ruptured
      aneurysms was the middle cerebral artery distribution (39%). Multiple aneurysms
      occurred in 22 (9.1%) cases. Other factors, such as medical history, coexisting
      disease, symptoms, activity at onset of symptoms, survival time, and toxicology
      results are also presented. Compared with literature reports before 1980, when
      ruptured cerebral artery aneurysms were reported as the cause of death in
      approximately 4% to 5% of sudden natural deaths, the results of this study
      suggest that despite improved diagnostic and therapeutic techniques during the
      past two decades, morbidity and mortality from ruptured aneurysms remain a
      significant health problem.

PMID- 11953487
TI  - Clinicopathologic features of fatal self-inflicted incised and stab wounds: a 20
      year study.
AB  - The files of the Forensic Science Center in Adelaide, South Australia, were
      examined for all cases listed as suicide in which death had been caused by the
      use of a sharp instrument during the 20-year period from January 1981 to December
      2000. Fifty-one cases were identified, consisting of 35 men and 16 women. The age
      range was 23 to 83 years (mean 49 years) representing 1.6% of total suicides
      (513182). Fatal injuries included incised wounds to the arms in 51.4% of men (n =
      1835) compared with 87.5% of women (n = 1416), incised and stab wounds to the
      neck in 40% of men (n = 1435) and 25% of women (n = 416), and stab wounds to the
      chest or abdomen in 28.6% of men (n = 1035) and 12.5% of women (n = 216). In 8
      cases, multiple sites were involved. The use of sharp instruments in suicide was
      favored by older, rather than younger, individuals, with a tendency for women to
      incise their wrists. Hesitation marks were present in 23 cases (54%) and scarring
      of the wrists from previous suicide attempts in 5 cases. Although this study
      demonstrated a higher number of men than women committing suicide by using sharp
      objects, this method of suicide remains uncommon.

PMID- 11953488
TI  - Forensic pathology on the threshold of the 21st century and the need for
      harmonization of current practice and training: the Greek concept.
AB  - Our era is characterized by the globalization of crime. This poses to all
      democratic countries the urgent need to reform their systems to fight crime more
      effectively. Forensic sciences remain an integral part of the system against
      crime. This scientific field can also offer valuable knowledge regarding the
      causes of death. From an epidemiologic point of view, this can result in better
      organization of prevention measures for the best interests of the community.
      Harmonization and collaboration in the operation of the various forensic systems
      that presently exist around the world is of paramount importance if effective
      prevention of crime and other causes of death in contemporary reality is to be
      achieved. In addition, revision of training in forensic pathology and forensic
      sciences is essential if harmonizing the forensic systems is to succeed. This
      report provides an overview of the wide variation in the operation of forensic
      systems and training. Emphasis is given to the importance of their harmonization,
      and an attempt is made to explore principles that may contribute along these
      lines. Finally, the authors provide proposals for revision of the training system
      in forensic pathology in Greece.

PMID- 11953489
TI  - Environmental gas displacement: three accidental deaths in the workplace.
AB  - The authors describe three accidental deaths resulting from occupational hazards
      involving environmental gas alterations. One involved the displacement of oxygen
      caused by leakage of liquid nitrogen during the installation of a magnetic
      resonance imaging system. Two involved elevated environmental carbon dioxide
      concentrations: dry ice sublimation in a walk-in refrigerator in a research
      laboratory, and activation of a carbon dioxide fire alarm-extinguisher system by
      a woman locked in a bank vault. The autopsy findings, scene investigations, and
      certifications of these deaths, as related to the mechanisms of death, are
      discussed.

PMID- 11953490
TI  - Neurocysticercosis.
AB  - Neurocysticercosis results when the ingested eggs of the pork tapeworm, Taenia
      solium, hatch into larval forms that penetrate the gut wall, disseminate
      hematogenously, and then encyst in the brain. The subsequent symptoms and
      associated morbidity are variable. Worldwide, cysticercosis is the most common
      parasitic disease affecting the central nervous system, but it is not a common
      autopsy finding in the United States. Neurocysticercosis may be an incidental
      finding, a contributing cause of death, or the underlying cause of death. It is
      also important for the forensic pathologist to be aware of the possibility of
      neurocysticercosis in the autopsy population for purposes of epidemiology studies
      and infection control. The authors use cases of neurocysticercosis found at
      autopsy at their institution to give examples of each scenario and to review the
      clinical and pathologic features of this parasitic disease.

PMID- 11953491
TI  - Personal identification based on radiographic vertebral features.
AB  - Personal identification of human remains constitutes about 10% of the normal
      caseload of any forensic medicine practice. Identification can be achieved by a
      variety of methods, one of which is the comparison of antemortem and postmortem
      radiographs. There are numerous accounts of cranial and dental radiographic
      features useful for identification, whereas the availability of postcranial
      radiographs and especially plates that depict the vertebral column is less
      widespread among the forensic community. The authors here review the various
      vertebral features instrumental in positive identification that can be identified
      on radiographs of the spine.

PMID- 11953492
TI  - Gasoline exposure in motor vehicle accident fatalities.
AB  - Three cases are described in which deaths after motor vehicle accidents occurred
      as a result of positional asphyxia associated with exposure to gasoline. The
      deceased individuals were aged 16, 34, and 35 years, respectively (M:F = 1:2) and
      had all been in the back seat of motor vehicles involved in rollover accidents
      that had resulted in spilling of gasoline with contamination of the cabins. Major
      components of gasoline were detected in blood and tissues by headspace gas
      chromatography. Postmortem toxicologic investigations of such cases, which
      include analyses for volatile hydrocarbons, may therefore produce additional
      significant information.

PMID- 11953493
TI  - Fatal childhood vascular injuries associated with seat belt use.
AB  - The deaths of two children who were passengers in motor vehicles involved in
      accidents were directly attributable to vascular injuries derived from seat
      belts. In the first case, a 10-year-old boy died as a result of abdominal aortic
      transection by a lap seat belt, and in the second case a 15-year-old boy died as
      a result of transection of his common carotid artery by a lap-shoulder seat belt.
      Although these cases demonstrate rare fatalities associated with seat belt use,
      there is no doubt that seat belts have significantly reduced mortality and
      morbidity from traffic accidents. Although it is possible that a fatal outcome
      might have occurred in each of these cases from other injuries that might have
      been sustained had seat belts not been worn, appropriate positioning and size of
      seat belt harnesses might have avoided the lethal injuries.

PMID- 11953494
TI  - Sudden unexpected death resulting from hypothalamic sarcoidosis.
AB  - The authors report a case of sudden death in a 23-year-old woman in whom autopsy
      by the medical examiner revealed hypothalamic sarcoidosis. The decedent had
      experienced 6 months of amenorrhea and a 50-pound weight gain. She sought medical
      attention when she experienced headache, and after imaging and laboratory
      studies, she was suspected of having neurosarcoidosis. She appeared to respond
      well to corticosteroid therapy. However, 6 weeks after the beginning of therapy,
      she was found dead on the floor of her residence. Autopsy showed extensive
      granulomatous inflammation of the hypothalamus and adjacent structures.
      Previously reported cases of hypothalamic sarcoidosis are reviewed. A hypothesis
      for the mechanism of sudden death is presented.

PMID- 11953495
TI  - The body buried twice.
AB  - The authors report the case of an unusual reason for an "exhumation." A young
      person "exhumed" a child's body involved in a road accident because he wanted to
      test methods for preventing or slowing down the process of postmortem decay.

PMID- 11953496
TI  - Suicidal decapitation by guillotine: case report.
AB  - A recently widowed man constructed a guillotine in the entrance to his cellar,
      having previously announced his intention to decapitate himself. A neighbor who
      saw the device from her house alerted the police. The deceased was found
      completely decapitated, still holding a pair of pliers that he had used to
      activate the mechanism. The findings of the resulting investigation are
      described, and the mechanism of suicidal decapitation is reviewed.

PMID- 11953497
TI  - Combination of DNA-based and conventional methods to detect human leukocyte
      antigen polymorphism and its use for paternity testing.
AB  - In cases of disputed paternity, the scientific goal is to promote either the
      exclusion of a falsely accused man or the affiliation of the alleged father.
      Until now, in addition to anthropologic characteristics, the determination of
      genetic markers included human leukocyte antigen gene variants; erythrocyte
      antigens and serum proteins were used for that reason. Recombinant DNA techniques
      provided a new set of highly variable genetic markers based on DNA nucleotide
      sequence polymorphism. From the practical standpoint, the application of these
      techniques to paternity testing provides greater versatility than do conventional
      genetic marker systems. The use of methods to detect the polymorphism of human
      leukocyte antigen loci significantly increases the chance of validation of
      ambiguous results in paternity testing. The outcome of 2384 paternity cases
      investigated by serologic and/or DNA-based human leukocyte antigen typing was
      statistically analyzed. Different cases solved by DNA typing are presented
      involving cases with one or two accused men, exclusions and nonexclusions, and
      tests of the paternity of a deceased man. The results provide evidence for the
      advantage of the combined application of various techniques in forensic
      diagnostics and emphasizes the outstanding possibilities of DNA-based assays.
      Representative examples demonstrate the strength of combined techniques in
      paternity testing.

PMID- 11953498
TI  - Sudden unexpected death resulting from previously nonsymptomatic subependymoma.
AB  - A 34-year-old, previously healthy man died suddenly and unexpectedly. The autopsy
      showed brain and pulmonary edema, numerous small meningeal meningiomas, bilateral
      and symmetrical juxtaventricular meningiomas, and a well-demarcated gray tan
      tumor in the medulla oblongata and upper cervical spinal cord. The latter tumor
      was a subependymoma with features of ependymoma in places. The authors describe
      and discuss the characteristics of this rare central nervous system tumor, its
      histogenesis, and its coexistence with other intracranial tumors. The possible
      mechanisms of death in the present case include compression of vital centers and
      acute obstruction of the cerebrospinal fluid flow.

PMID- 11953499
TI  - Unusual neck lesion in a pedestrian caused by a road accident.
AB  - The authors describe a road accident that occurred in the Trieste region of Italy
      in 1998, wherein a pedestrian experienced a mortal injury. During the on-site
      examination, the forensic officer in charge noticed, in addition to dispersed
      abrasions, bruises, and fractures, an unusual position of the head with a highly
      unusual motility of the cervical rachis and, above all, an apparent whitish
      fibrous elastic cord, 7-8 cm long, which came out of the mouth. The cord was
      found to be a segment of the spinal cord, expelled and driven into the mouth
      cavity by the impact. This represents an interesting case because of the specific
      dynamics of the accident and the type of lesion involved. This kind of spinal
      cord injury, in particular, is infrequent among pedestrians involved in road
      accidents in comparison with other road casualties.

PMID- 11953500
TI  - Is immunohistochemistry a useful tool in the postmortem recognition of myocardial
      hypoxia in human tissue with no morphological evidence of necrosis?
AB  - Myocytes in the border zone of myocardial infarction are under severe hypoxia
      without characteristic morphology of necrosis, and show ultrastructural features
      similar to those seen within the first hours after coronary occlusion. This study
      was carried out to evaluate the possibility that immunohistochemical methods
      could be used for the early diagnosis of myocardial infarction by detecting areas
      of hypoxia. Nineteen human sections of formalin-fixed paraffin-embedded
      myocardial samples showing a necrotic area and its border were submitted to
      immunohistochemical staining with the markers antimuscle actin, antimyoglobin,
      antitroponin T, antifibronectin, and anticomplement component C9. Sections were
      also subjected to azan trichrome and hematoxylin-basic fuchsin-picric (HBFP)
      staining techniques. Immunohistochemistry and azan trichrome showed that in the
      border zone there was a pattern of reaction intermediate between the infarcted
      area and the normal myocardium. The HBFP failed to distinguish these two areas.
      In conclusion, immunohistochemistry and azan trichrome can recognize myocardial
      hypoxia. Because hypoxia is an invariable condition in infarction, these
      techniques can be used to confirm suspected cases of myocardial infarction in
      which necrosis is not yet evident. However, considering that agonal states may be
      associated with generalized hypoxia, further studies are needed to confirm the
      reliability of this procedure in the earlier phases of myocardial infarction.

PMID- 11953501
TI  - Cardiac rupture in acute myocardial infarction: a reassessment.
AB  - Cardiac rupture as a complication of acute myocardial infarction (AMI) has been
      described as occurring infrequently. Because of the recent dramatic decrease in
      autopsy rates, the authors believe that current studies do not accurately
      represent the frequency of this catastrophic complication. Autopsy protocols and
      archived histologic slides of patients with AMI were retrospectively reviewed to
      determine whether the frequency of cardiac rupture, as a complication of AMI, is
      altered when a non-hospital-based patient cohort after autopsy is evaluated. This
      review yielded 153 cases of 41 women and 112 men, whose postmortem examinations
      revealed gross and histologic evidence of AMI. Cardiac rupture was present in
      30.7% of these cases. Of the 47 patients with rupture, 35 had no relevant medical
      history. The remaining 12 patients had various medical conditions. None of the
      patients in the rupture group had previously treated symptoms related to coronary
      artery conditions. Whereas women constituted 26.8% of the total AMI group, they
      had a cardiac rupture rate of 61%. By contrast, men with AMI had a cardiac
      rupture rate of 19.6%. All patients in the cardiac rupture group had heart
      weights over the predicted expected weight as a function of body weight. Age,
      gender, and heart weight were significant factors associated with cardiac
      rupture, whereas body mass index was not significantly related. When these
      factors were evaluated jointly, age was a significant explanatory factor for
      rupture among both men and women, whereas body mass index and heart weight were
      significant for men but not for women. When the rupture sites occurred on the
      left ventricular myocardium, the anterior wall was affected in 21 cases (45%),
      the posterior wall in 18 (38%), the lateral wall in 4 (9%), and the apex in 3
      (6%). The right ventricular myocardium ruptured in 1 case (2%). Most of the
      patients had severe multivessel coronary artery disease. Histologic study of the
      specimens showed that the majority of ruptures occurred between 24 and 72 hours
      after myocardial infarction. This study showed a frequency of cardiac rupture of
      30.7% in patients with AMI and sudden death according to medical examiner's
      records. These findings confirm and reinforce the importance of postmortem
      examination and autopsy as an adjunct to clinical medical practice.

PMID- 11953502
TI  - Sudden death resulting from lesions of the cardiac conduction system.
AB  - Sudden unexpected deaths in young persons with noncontributory histories, autopsy
      results, and drug screen results are a common problem in forensic pathology. As
      part of the evaluation of such cases, the cardiac conduction system (CCS) should
      be studied. To determine the type and incidence of lethal CCS lesions, the
      authors reviewed their files of sudden unexpected cardiac deaths with particular
      attention to cases with causes of death in the conduction system. Cases of sudden
      cardiac death in patients aged < or=40 years during a 10-year period (Michigan)
      and a 4 year-period (Spain) were selected from the files. From this group, cases
      were identified in which the cause of death was a lethal change in the CCS. The
      portions of the heart containing the CCS were excised, and at least one
      hematoxylin and eosin slide and at least one trichrome or elastic trichrome slide
      per block were studied. In the two centers, 381 cases of sudden cardiac death
      were identified. The most common causes of sudden cardiac death were
      arteriosclerotic narrowing of the coronary arteries, cardiomyopathy, and
      myocarditis. In 82 cases, there was no identifiable cause of death even after
      complete gross and microscopic autopsy was performed, a medical history was
      obtained, and a drug screen was performed. In 11 cases, the CCS contained lesions
      that were considered lethal: narrowing of the atrioventricular node artery by
      fibromuscular hyperplasia (7 cases) and atrioventricular node tumors (4 cases).
      The 11 cases accounted for 2.9% of the 381 cases of sudden cardiac death and
      11.8% of the indeterminable cases. It was concluded that examination of the CCS
      in deaths in which the gross and microscopic autopsy, history, and drug screen
      fail to provide a cause of death can yield a cause of death in a significant
      percentage of cases. If heart block was not documented during life and no
      explanatory lesions were found during routine cardiac examination, examination of
      the CCS can yield valuable information.

PMID- 11953503
TI  - NAME and its history: implications for the future.

PMID- 11953504
TI  - An inherited metabolic disorder presenting as ethylene glycol intoxication in a
      young adult.
AB  - Despite the abundance of reports emerging in the literature on metabolic
      disorders, some disorders remain undiagnosed or misdiagnosed, not only in
      clinical pathology but also in forensic pathology. The authors report a patient
      who had recurrent episodes characterized by nausea, vomiting, and signs of
      dehydration necessitating admission to the hospital. At each admission, he was
      found to have lactic acidosis. On the first admission, glycolic acid was detected
      in his blood and he was diagnosed as having ethylene glycol intoxication. Only at
      the third admission, 2 years after the first, was the possibility of an
      underlying metabolic disorder considered. Laboratory investigations showed a
      deficiency of complex I in the mitochondrial oxidative phosphorylation. Possible
      medicolegal implications are discussed.

PMID- 11953505
TI  - Chronic lead poisoning: induced psychosis in an adult?

PMID- 11953506
TI  - Fatal pediatric head injuries caused by short distance falls.

PMID- 11953507
TI  - Symptoms following head injury.

PMID- 11953508
TI  - Living with illness. Is nursing care adequately addressing the needs of the
      chronically ill?

PMID- 11953509
TI  - Nursing school a la carte. There's more than one way to become a nurse.

PMID- 11953512
TI  - When it's time to clean out the medicine cabinet.

PMID- 11953511
TI  - Elderly patients with diabetes. What you should ask your patient on the next
      visit.

PMID- 11953513
TI  - The Nationwide State Legislative Agenda.

PMID- 11953515
TI  - Morphine. Now.

PMID- 11953516
TI  - Making diabetes management routine.

PMID- 11953518
TI  - An Afghan hospital in wartime. Nurses, physicians, and wounded fighters--a photo
      essay.

PMID- 11953517
TI  - Hypoglycemia unawareness.

PMID- 11953519
TI  - ICD therapy: the patient's perspective.

PMID- 11953520
TI  - Smallpox.

PMID- 11953521
TI  - Nursing smallpox and its consequences. February 1921.

PMID- 11953522
TI  - A small-pox experience in California. February 1912.

PMID- 11953523
TI  - Monitoring sedation.

PMID- 11953524
TI  - Negotiating a salary.

PMID- 11953525
TI  - Rhabdomyolysis: an overview.

PMID- 11953527
TI  - Our worst disaster's first nurse. Interview by Maureen Shawn Kennedy.

PMID- 11953526
TI  - Nursing magnets: attracting talent and making it stick.

PMID- 11953528
TI  - Make sure you're an OSHA statistic.

PMID- 11953530
TI  - Acute renal failure: early detection and prompt intervention can improve
      outcomes.

PMID- 11953531
TI  - Sex and the oncology patient: discussing sexual dysfunction helps the patient
      optimize quality of life.

PMID- 11953532
TI  - Chemotherapy-induced neurotoxicity: assessment and interventions for patients at
      risk.

PMID- 11953533
TI  - Stomatitis: an overview: protecting the oral cavity during cancer treatment.

PMID- 11953534
TI  - Managing pain in outpatients: there are particular challenges to pain control in
      outpatient settings.

PMID- 11953535
TI  - Living with fatigue: managing cancer-related fatigue at home and in the
      workplace.

PMID- 11953537
TI  - Multidisciplinary patient care: one institution's approach offers personal
      treatment.

PMID- 11953536
TI  - Symptom management in radiation oncology: acute and long-term side effects.

PMID- 11953538
TI  - Improving the quality of life through education: a pilot program of symptom
      management classes for oncology patients.

PMID- 11953539
TI  - Speaking the unspeakable for end-of-life patients: Lisa's story illustrates how
      nurses facilitate communication.

PMID- 11953540
TI  - Reducing the risk of falls through proprioceptive dynamic posture training in
      osteoporotic women with kyphotic posturing: a randomized pilot study.
AB  - OBJECTIVE: To assess the effect of a proprioceptive dynamic posture training
      program on balance in osteoporotic women with kyphotic posture. DESIGN: Subjects
      were randomly assigned to either a proprioceptive dynamic posture training
      program or exercise only group. Anthropometric measurements, muscle strength,
      level of physical activity, computerized dynamic posturography, and spine
      radiography were performed at baseline and 1 mo. RESULTS: At the 1-mo follow-up,
      three groups were formed on the basis of the baseline computerized dynamic
      posturography results. In general, groups 1 and 2 had no significant change at 1
      mo, whereas group 3 improved balance significantly at 1 mo. CONCLUSION: The
      subjects who had abnormal balance and used the proprioceptive dynamic posture
      training program had the most significant improvement in balance. Improved
      balance could reduce the risk of falls.

PMID- 11953542
TI  - Chronaxie and accommodation index in the diagnosis of muscle denervation.
AB  - OBJECTIVE: To determine the sensitivity of the combined measurement of chronaxie
      and the accommodation index in the qualitative diagnosis of muscle denervation
      with needle electromyography and to compare quantitative diagnoses. DESIGN:
      Ninety-three neurogenic muscles diagnosed by needle electromyography were
      consecutively included for measurement of chronaxie and the accommodation index
      in this prospective study. The sensitivity of qualitative diagnosis was assessed
      for all muscles, separately for the acute and subacute-chronic denervation phase
      and for the complete and partial denervation. RESULTS: The combined measurement
      of chronaxie and the accommodation index showed a 90% sensitivity to needle
      electromyography for qualitative diagnosis of muscle denervation for all muscles.
      A 100% sensitivity was found for the acute denervation phase and for complete
      denervation. The subacute-chronic denervation phase revealed a 86% sensitivity,
      and partial denervation had a 88% sensitivity. The kappa coefficients did not
      show satisfactory agreement in quantitative diagnosis, and Bowker's test revealed
      a statistically significant underestimation of muscle denervation for measurement
      of chronaxie. CONCLUSION: The combined measurement of chronaxie and the
      accommodation index can be recommended for the screening of neurogenic lesions in
      the acute denervation phase.

PMID- 11953541
TI  - Benefits of home visits for falls and autonomy in the elderly: a randomized trial
      study.
AB  - OBJECTIVE: To investigate whether home visits by a occupational therapist reduces
      the risk of falling and improves the autonomy of older patients hospitalized for
      falling. DESIGN: In this randomized, controlled trial set in a geriatric
      hospital, 60 patients (mean age, 83.5 yr) who were hospitalized for falling were
      recruited from the acute medicine department. A home visit from an occupational
      therapist and an ergotherapist assessed patients' homes for environmental hazards
      and recommended modifications. The outcomes measured were falls, autonomy,
      hospitalization for falling, institutionalization, and death. RESULTS: During the
      follow-up period, the rate of falls, hospitalization for falls,
      institutionalization, and death were not significantly different between the two
      groups. Both groups had a loss of dependence at 12 mo. This loss of dependence
      was significant in the control group but not in the intervention group.
      CONCLUSIONS: Home visits from occupational therapists during hospitalization of
      older patients at risk for falling can help to preserve the patient's autonomy.

PMID- 11953543
TI  - Aerobic work capacity in elite wheelchair athletes: a cross-sectional analysis.
AB  - OBJECTIVE: To give a descriptive analysis of aerobic capacity among elite
      wheelchair athletes in association with various personal characteristics and
      sprint or anaerobic capacity. DESIGN: Sixty-eight wheelchair athletes who
      participated in the World Games and Championships for the Disabled were included.
      Parameters for aerobic capacity were evaluated in a standardized wheelchair
      exercise test on a computer-controlled wheelchair ergometer at the games. The
      ergometer setting was individually tuned according to standardized procedures.
      RESULTS: Mean maximum power output was 72.2 +/- 36.7 W. Peak oxygen uptake showed
      similar strong variations among different subject groups. High values were seen
      in a group of six subjects with amputations. Results stressed that, apart from
      sex, functionality and training status had a strong influence on aerobic
      capacity. Anaerobic and aerobic capacity were strongly associated. CONCLUSIONS:
      Functionality, training status, and sex are important determinants of aerobic
      capacity. The functional classification used at international sports events is
      represented in the data, and further study into the possible contribution of
      standardized exercise tests within the issue of classification must be
      considered. The use of standardized exercise tests for the evaluation of training
      and for rehabilitation progress must be advocated, with power output being an
      important outcome measure at the level of ability, whereas oxygen uptake
      represents outcome at the level of organ systems.

PMID- 11953544
TI  - Effect of intramuscular botulinum toxin injection on upper limb spasticity in
      stroke patients.
AB  - OBJECTIVE: To evaluate the therapeutic effect of intramuscular injection of
      botulinum toxin on spasticity of the upper limb, with emphasis on its influence
      over limb function. DESIGN: An open-label, noncontrolled trial with a duration of
      12 wk was designed to determine the safety and efficacy of intramuscular
      botulinum toxin A injection in the treatment of 16 patients with stroke with
      spastic hemiparesis. Electromyographically guided intramuscular botulinum toxin A
      injections were applied to the spastic limbs. A detailed scale system was used
      for the evaluation of muscle tone and functional changes induced by botulinum
      toxin A treatment. RESULTS: No major side effect secondary to botulinum toxin A
      injection was reported. Statistically significant (P < 0.05) improvements of
      muscle tone, joint range of motion, hand muscle strength, and muscular pain were
      seen after the injection. The improvements lasted up to 8-12 wk after the
      treatment. However, there was no significant functional improvement except in two
      of the patients. CONCLUSIONS: Botulinum toxin A injection may help relieve upper
      limb spasticity and pain in patients with stroke. Its effect on function is
      probably determined by case selection.

PMID- 11953545
TI  - Stroke rehabilitation outcome study: a comparison of Japan with the United
      States.
AB  - OBJECTIVE: To compare demographics and functional outcomes in stroke
      rehabilitation in Japan and the United States. DESIGN: In Japan, 464 consecutive
      patients with first stroke were enrolled. The United States data were collected
      from the ninth annual report on patients discharged from medical rehabilitation
      hospital programs in the United States that subscribe to the Uniform Data System
      for Medical Rehabilitation. RESULTS: There are many differences between the two
      countries. Japanese survivors were 10 yr younger, were admitted to the
      rehabilitation hospital after a markedly longer period of time after the onset of
      the stroke, had comparably severe impairment on admission, had markedly longer
      lengths of stay, and had relatively severe disability at discharge. The mean or
      median admission FIM total score was comparable between Japan and the United
      States. The mean or median discharge FIM total score of Japanese patients was
      similar to that of the United States. CONCLUSIONS: This may account for the lower
      rehabilitation efficiency for the Japanese patients. Mean admission FIM total
      scores in Japan were approximately the same as the discharge FIM scores in the
      United States data. Rate of discharge to the community was higher in Japan than
      in the United States.

PMID- 11953546
TI  - Effects of functional electric stimulation on upper limb motor function and
      shoulder range of motion in hemiplegic patients.
AB  - OBJECTIVES: The present study examines functional electric stimulation (FES)
      applied on patients with hemiplegia of short and long duration for the purpose of
      upper limb motor recovery and increasing shoulder range of motion. DESIGN:
      Patients with hemiplegia with subluxation participating in the study were placed
      into a short-duration group or a long-duration group. Subjects in each group were
      then randomly assigned to either the control or the experimental subgroup. The
      experimental groups of both short- and long-duration groups received FES therapy
      in which the supraspinatus and posterior deltoid muscles were induced to contract
      repetitively up to 6 hr a day for 6 wk. Duration of FES session and muscle
      contraction/relaxation ratio were progressively increased as performance
      improved. The experimental groups also received a second 6-wk FES therapy 6 wk
      after completing the first FES therapy. RESULTS: After the first 6-wk FES
      therapy, the experimental group of short-duration hemiplegia showed significant
      improvements in motor recovery as indicated by Fugl-Meyer scores compared with
      the control group. Such significant improvement did not occur for the
      experimental group of long-duration hemiplegia. The changes in the second FES
      treatment program were insignificant. CONCLUSIONS: This study suggests that
      patients with hemiplegia of short duration are effectively trained by FES for
      motor recovery.

PMID- 11953547
TI  - Pain treatment in persons with cerebral palsy: frequency and helpfulness.
AB  - OBJECTIVES: To identify the interventions currently being used by adults with
      cerebral palsy (CP) for pain management, examine the perceived helpfulness of
      these interventions, and determine the extent to which these individuals with
      cerebral palsy-related pain were accessing the services of healthcare providers
      for the explicit purpose of addressing pain. DESIGN: Retrospective, descriptive
      study of 64 adults with cerebral palsy-related chronic pain. Subjects ranged in
      age from 18 to 76 yr and included 35 women and 29 men. Subjects were evaluated by
      using a protocol-based interview. RESULTS: The study sample sought and used a
      variety of pain treatments and healthcare providers and rated many of the
      interventions as being at least moderately helpful. Despite the reported
      helpfulness of the pain interventions, however, most are only being used by a
      small subset of the sample. CONCLUSION: The majority of the sample with chronic
      pain did not access healthcare providers for help in managing their pain.
      Cerebral palsy-related pain is undertreated in the adult population with cerebral
      palsy.

PMID- 11953548
TI  - Risk factors of cerebral palsy in preterm infants.
AB  - OBJECTIVE: To investigate the outcome of preterm infants and to determine the
      most important risk factors in the development of cerebral palsy. DESIGN: The
      outcomes of 437 survivors of preterm infancy (gestational age at birth, <36 wk)
      born in one center in Korea were reviewed in relation to the clinical risk
      factors in the perinatal period and neonatal cerebral ultrasound lesions that
      occurred over a 3-yr period. The odds ratios of risk factors for the development
      of cerebral palsy were calculated. RESULTS: A total of 4.8% of all survivors
      subsequently developed cerebral palsy. The prevalence of cerebral palsy was 12%
      in infants that weighed <2000 g at birth, but it was only 0.4% in those that
      weighed >2000 g. Preterm labor, preterm rupture of membrane, severe birth
      asphyxia, neonatal sepsis, and respiratory distress syndrome had stronger
      correlations with the development of cerebral palsy. A total of 56% of infants
      having periventricular leukomalacia and 53% of those having grade 3
      intraventricular hemorrhage developed cerebral palsy. The infants with cystic
      lesions had higher rates of the quadriplegic type and were more severely
      disabled. CONCLUSION: The existence of periventricular leukomalacia was the
      strongest and most independent risk factor for the subsequent development of
      cerebral palsy. The grade of periventricular leukomalacia was significantly
      correlated with the clinical type and severity of cerebral palsy.

PMID- 11953549
TI  - Motor function improvement following intrathecal baclofen pump placement in a
      patient with locked-in syndrome.
AB  - We describe a patient with locked-in syndrome who had minimal volitional motor
      function and severe spasticity in all four extremities. The patient showed a
      significant improvement in volitional motor function following intrathecal
      baclofen pump therapy to control spasticity. This case study suggests that
      intrathecal baclofen pump therapy might improve motor function in select patients
      with locked-in syndrome.

PMID- 11953550
TI  - Influence of rotators on the kinematic adaptations in stubby prosthetic gait.
AB  - We report on the results of gait analysis in a patient with bilateral knee
      disarticulation amputations who used short nonarticulated prosthetic limbs
      (stubbies) to meet his ambulation needs over an extended period. To compensate
      for the loss of knee and ankle articulations, exaggerated pelvic obliquity (hip
      hiking), transverse pelvic rotation, and hip abduction were needed to ensure limb
      clearance and a functional step length. The addition of rotators to the
      prostheses improved gait velocity and reduced the perceived exertion of walking
      by favorably altering center of mass energetics.

PMID- 11953551
TI  - Exertional compartment syndrome and the role of magnetic resonance imaging.
AB  - A 47-yr-old woman presented with a 1-yr history of progressive bilateral anterior
      lower leg pain and swelling with walking, which resolved 10 min after activity.
      Postexercise (forced dorsiflexion) magnetic resonance imaging revealed increased
      T2 signal intensity in the entire anterior muscle compartment, and anterior
      compartment pressures were elevated at rest and postexercise. Chronic exertional
      compartment syndrome can occur in some patients after even minimal physical
      activities, and magnetic resonance imaging without the use of radioisotopes was a
      useful adjunct for diagnosis.

PMID- 11953552
TI  - Functional performance deficits in athletes with previous lower extremity injury.
AB  - OBJECTIVE: To evaluate the influence of previously treated, though clinically
      resolved, lower extremity injury on performance in a timed 20-meter shuttle run.
      DESIGN: Case control study. SETTING: National Collegiate Athletic Association
      (NCAA) Division I college during the 2000/2001 preparticipation physicals.
      PARTICIPANTS: NCAA Division I athletes (n = 213) participated in this research
      study. Athletes were excluded if they presently had an unresolved lower extremity
      injury or low back pain. MAIN OUTCOME MEASURES: Time to complete a 20-meter
      shuttle run was recorded. Previous lower extremity injury and college year were
      recorded via a short questionnaire. RESULTS: A significantly slower response time
      on the 20-meter shuttle run was observed in freshman athletes with a history of a
      lower extremity injury, as compared with freshmen without a previous injury (p =
      0.01). No significant difference was noted in non-freshman collegiate athletes
      regardless of injury history (p = 0.98). CONCLUSION: Kinetic chain deficits may
      exist long after symptomatic recovery from injury resulting in functional
      deficits, which may be missed on a standard physical assessment. The slower
      shuttle run times observed in freshmen with previous lower extremity injury may
      be a manifestation of insufficient treatment received at the high school level or
      the benefit of a mandatory core strengthening program in returning athletes.
      Further study is necessary to identify and validate the cause-and-effect
      relationship. CLINICAL RELEVANCE: This study may support residual functional
      deficits in incoming college athletes, which may be related to inadequate care in
      the high school setting.

PMID- 11953553
TI  - Comparison of scintigraphy and magnetic resonance imaging for stress injuries of
      bone.
AB  - OBJECTIVE: To compare findings of radiography, scintigraphy, and magnetic
      resonance imaging (MRI) in stress injuries of bone and evaluate changes of these
      findings with time correlated with clinical symptoms. DESIGN: Prospective study.
      SETTING: A primary care hospital outpatient orthopedic clinic. PATIENTS: All 31
      patients with stress injuries of bone who visited our clinic from July 1996 to
      June 2000. INTERVENTION: Radiography, scintigraphy, MRI, and clinical
      examinations were performed on the same day or at least within 1 week of each
      other, and the findings were compared. If symptoms of stress injury of bone
      continued, these examinations were repeated at intervals of 2 months until
      symptoms disappeared. These radiologic findings were assessed by an independent
      radiologist who was blinded to the clinical symptoms of the patients. MAIN
      OUTCOME MEASURES: Correlation accuracy of MRI and scintigraphy findings with
      clinical symptoms. RESULTS: Even with negative initial radiographic findings, all
      initial scintigraphy and MRI indicated stress injury of bone. There were no
      patients with positive/negative examinations. Grade of scintigraphy and MRI were
      closely correlated, and these findings also correlated with the degree of
      clinical symptoms. Compared with scintigraphy, MRI showed more diagnostic
      information, such as fracture line and periosteal edema. Areas of increased
      activity in scintigraphy were consistent with the grades of MRI, especially high
      signal intensity areas of STIR (short tau inversion recovery) image. CONCLUSIONS:
      From these observations, MRI is less invasive, provides more information than
      scintigraphy, and is recommended for initial diagnosis and assessment stages of
      stress injury of bone.

PMID- 11953554
TI  - Efficacy of stairclimber versus cycle ergometry in postoperative anterior
      cruciate ligament rehabilitation.
AB  - OBJECTIVE: To examine the effective use of stair climbing as an alternative to
      cycling for knee rehabilitation in an actual injured sport population. DESIGN:
      Repeated-measures multivariate analyses with data collected during anterior
      cruciate ligament (ACL) rehabilitation. SETTING: Clinical rehabilitation setting
      following ACL reconstruction. PARTICIPANTS: 46 athletes with ACL reconstruction
      (32 males, 14 females; age 25.5 +/- 8.9 yrs) were randomly assigned to either
      cycle or stairclimber programs previously matched by metabolic equivalents (METs)
      and heart rate. MAIN OUTCOME MEASURES: Isokinetic testing was performed at 4 and
      12 weeks postoperatively on the uninjured knee to safely determine mean and peak
      concentric quadriceps, eccentric quadriceps, concentric hamstring, and eccentric
      hamstring peak torques. Pre/post leg girths were also measured bilaterally (+7.6,
      +15.2, +22.9, -7.6, -15.2, -22.9 cm) proximal/distal to the patella. RESULTS:
      Multivariate analysis of variance indicated no differences (Wilks' Lambda F(8,37)
      = 1.461; p = 0.21; eta(2) = 0.240; Power = 0.556) in strength gains (NM) between
      cycle and stair climbing groups, respectively, in mean concentric quadriceps
      (58.4 +/- 12.0 vs. 37.1 +/- 13.2), peak concentric quadriceps (77.0 +/- 14.7 vs.
      36.8 +/- 16.2), mean eccentric quadriceps (57.2 +/- 12.7 vs. 79.2 +/- 14.0), peak
      eccentric quadriceps (78.6 +/- 19.3 vs. 105.5 +/- 21.3), mean concentric
      hamstring (14.3 +/- 3.9 vs. 6.5 +/- 4.3), peak concentric hamstring (24.0 +/- 6.7
      vs. 22.2 +/- 7.4), mean eccentric hamstring (22.6 +/- 8.6 vs. 23.8 +/- 9.5), or
      peak eccentric hamstring (23.5 +/- 11.2 vs. 36.7 +/- 12.3) response. A
      significant stair climbing effect (Wilks' Lambda F(6,37) = 2.95; p = 0.02; eta(2)
      = 0.324; Power = 0.843) was observed in gastrocnemius girth (-15.2 cm) in both
      injured (0.5 +/- 0.1 cm vs. 0.3 +/- 0.1 cm, p < 0.04) and non-injured (0.3 +/-
      0.1 cm vs. 0.0 +/- 0.1 cm, p < 0.008) legs. CONCLUSIONS: In conclusion, the
      results of the data suggest no deleterious effect of stair climbing on knee
      isokinetic performance or limb girth measurements, and confirms the use of stair
      climbing as a viable adjunct/alternative to cycle ergometry in ACL-injured
      athletes.

PMID- 11953555
TI  - Sports activity of patients with idiopathic scoliosis at long-term follow-up.
AB  - OBJECTIVE: The aim of the study was to assess long-term the sports activities of
      operatively and nonoperatively treated patients with idiopathic scoliosis and
      compare these activities with those of controls. STUDY DESIGN: Cross-sectional
      case-control study, performed at The Orthopaedic University Hospital Heidelberg.
      PATIENTS AND METHODS: The study enrolled 59 patients (53 female, 6 male; mean age
      43 years) with idiopathic scoliosis and a minimum follow-up of 5 years (mean 22
      years) since treatment (28 nonoperative, 31 operative). Mean Cobb angle at the
      time of the study was 54 degrees. An age-adjusted control group (n = 33) with no
      history of spinal disorder was evaluated at the same time. All participants in
      the study (n = 92) completed a questionnaire assessing spinal function (Spine
      Score) and sporting activity (Sport Score). In addition, the scoliosis patients
      underwent radiographic evaluation of their spine. The groups were compared by
      analysis of variance. In order to assess the relationship between two variables,
      Spearman's correlation coefficient was calculated. RESULTS: Both groups of
      scoliosis patients attained a lower Sport Score than the controls (p < 0.015 and
      p < 0.006, respectively). There was no difference between the two scoliosis
      groups. Reduced spinal function correlated with reduced sports activity (p <
      0.001). In both scoliosis groups, the subscales "back pain" and "physical
      activity" correlated with sporting activity (p < 0.03 and p < 0.02,
      respectively). In the surgically treated patients, Cobb angle correlated with
      reduced sports activity (p < 0.03). The extent of the spinal arthrodesis (number
      of segments) in surgically treated patients had no effect on their sports
      activity. CONCLUSIONS: Over the long term, patients with idiopathic scoliosis
      suffer impairment of their sports activities compared with age-matched controls.
      The main reasons for this are functional impairment and the frequency of back
      pain. Sports activity is not more restricted after extended spinal fusion than it
      is after nonoperative treatment.

PMID- 11953556
TI  - Predictors of lower extremity injury among recreationally active adults.
AB  - OBJECTIVE: To identify gender-specific predictors of lower extremity injury among
      a sample of adults engaging in running, walking, or jogging (RWJ) for exercise.
      DESIGN: Prospective cohort study. SETTING: Cooper Clinic Preventive Medicine
      Center, Dallas, Texas. PARTICIPANTS: Participants were 2,481 men and 609 women
      who underwent a physical examination between 1970 and 1981 and returned a follow
      up survey in 1986. Predictor variables measured at baseline included height,
      weight, and cardiorespiratory fitness. At follow-up, participants recalled
      information about musculoskeletal injuries, physical activity levels, and other
      predictors for lower extremity injury over two time periods, 5 years and 12
      months. MAIN OUTCOME MEASURES: An injury was defined as any self-reported lower
      extremity injury that required a consultation with a physician. Cox proportional
      hazards regression (HR) was used to predict the probability of lower extremity
      injury for the 5-year recall period, and unconditional logistic regression was
      used for the 12-month recall period. RESULTS: Among men, previous lower extremity
      injury was the strongest predictor of lower extremity injury (HR = 1.93-2.09),
      regardless of recall period. Among women, RWJ mileage >20 miles/wk was the
      strongest predictor for the 5-year period (HR = 2.08), and previous lower
      extremity injury was the strongest predictor for the 12-month period (HR = 2.81).
      CONCLUSIONS: For healthy adults, walking at a brisk pace for 10-20 miles per week
      accumulates adequate moderate-intensity physical activity to meet national
      recommendations while minimizing the risk for musculoskeletal lower extremity
      injury. Clinicians may use this information to provide appropriate injury
      prevention counseling to their active patients.

PMID- 11953557
TI  - Comparing injuries of spin bowling with fast bowling in young cricketers.
AB  - OBJECTIVE: To compare the incidence and anatomic distribution of injuries
      sustained in spin and fast bowling in young cricketers. DESIGN: A prospective
      cohort study. Physical characteristics and retrospective data (sporting
      involvement and previous injuries) from young cricketers were recorded. The
      cohort of young cricketers was divided according to style of bowling into a group
      of spin bowlers and a group of fast bowlers. Data from the spin bowler group was
      compared with the data from the fast bowler group to assess whether these groups
      were matched. A prospective study of injuries sustained by the bowlers was then
      undertaken. Data regarding cricket played and injuries sustained were collected
      by telephone questionnaire every 6 weeks for 6 months from each bowler. SETTING:
      Bowlers were recruited from young cricketers training at Centers of Excellence of
      3 "First Class" Counties in England in January 1998. PARTICIPANTS: There were 42
      spin bowlers and 70 fast bowlers. The mean age was 14.9 years (range 9 to 21
      years). MAIN OUTCOME MEASURES: Injuries caused by bowling and interfering with
      bowling are included in incidence data. The number of deliveries bowled in
      matches and practice is used as the denominator for the reported incidence.
      RESULTS: Telephone follow-up was achieved when planned on 98.2% of occasions.
      There were 29 injuries meeting the criteria above. The incidence of injury in
      spin bowlers was 0.066 per 1,000 balls and 0.165 per 1,000 balls in fast bowlers
      (p = 0.097 Wilcoxon rank sum test). The incidence of injury (per 1,000 balls) at
      various anatomic sites in fast bowling was knee 0.057, ankle 0.043, low back
      0.029, and shoulder 0.007. In spin bowlers, the site incidence was shoulder 0.055
      and low back 0.011. The percentage with injuries at ankle, knee, and shoulder was
      significantly different (95% confidence intervals) for fast and spin bowlers. A
      significant difference was not found for lower back injuries. CONCLUSIONS:
      Incidence of injuries in fast bowling is greater than in spin bowling (but this
      was not a significant difference within the limits of this study). Low back
      injuries in fast bowlers have been the subject of published research. However,
      injuries in spin bowling have not previously been described, and this study
      indicates that shoulder injuries in wrist spinners merit further study.

PMID- 11953558
TI  - Significant enhancements in glucose tolerance and insulin action in centrally
      obese subjects following ten days of training.
AB  - OBJECTIVE: The objective of the study was to determine the effects of short-term
      exercise on glucose tolerance and insulin response to a glucose load in centrally
      obese individuals. DESIGN: 75 g oral glucose tolerance tests (OGTT) were
      performed prior to participation and 24 hours after the last exercise session.
      Exercise bouts were 40 minutes in duration and consisted of treadmill walking and
      cycle ergometry at 70-80% of age-predicted maximum heart rate (APHR(max)).
      PARTICIPANTS: Eleven sedentary, centrally obese men [mean (SE): Mass, 119.1 (5.4)
      kg; BMI, 37.7 (1.8) kg/m(-2); waist-to-hip ratio (WHR), 0.97 (0.01); age 31.7
      (2.4) years] were studied before and after 10 days of aerobic exercise training.
      RESULTS: No significant change (p >.05) in body mass was noted following 10 days
      of exercise as compared with preparticipation [119.1 (5.4) kg versus 118.9 (5.4)
      kg]. Fasting plasma glucose concentration was significantly lower (p < 0.05)
      following 10 days of exercise as compared with preexercise [5.58 (0.15) mmol/L
      versus 5.27 (0.12) mmol/L]. No significant change (p > 0.05) in fasting plasma
      insulin concentration, however, was observed following 10 days of exercise
      training as compared with preexercise [276.2 (33.7) pmol/L versus 225.3 (35.9)
      pmol/L]. Plasma insulin concentrations at 60 minutes and 120 minutes were
      significantly decreased (p < 0.05) when comparing the preexercise to the
      postexercise OGTT [60: 1264.2 (88.3) pmol/L versus 1103.5 (81.1) pmol/L; 120:
      1066.9 (110.5) pmol/L versus 764.1 (106.2) pmol/L]. Plasma glucose concentration
      at 120 minutes. was also significantly reduced (p < 0.05) after 10 days of
      exercise as compared with preexercise [6.09 (0.24) mmol/L versus 5.39 (0.22)
      mmol/L]. Area under the glucose curve was significantly (p < 0.05) reduced after
      10 days of exercise as compared with preparticipation [944.6 (44.4) mmol/L/120
      min versus 884.4 (43.2) mmol/L/120 min]. Area under the insulin curve was also
      significantly decreased (p < 0.05) following 10 days of exercise training as
      compared with preexercise [126,890 (9014.0) pmol/L/120 min versus 109,445
      (7,888.9) pmol/L/120 min]. CONCLUSIONS: These data suggest that short-term
      exercise may improve glucose tolerance and insulin response to a glucose load in
      centrally obese men.

PMID- 11953559
TI  - Spondylolysis in the adolescent athlete.

PMID- 11953560
TI  - The initial lateral cervical spine film for the athlete with a suspected neck
      injury: helmet and shoulder pads on or off?

PMID- 11953561
TI  - Two unusual cases of acetabular fractures sustained during sports.

PMID- 11953562
TI  - Quadratus femoris strain.

PMID- 11953563
TI  - Unilateral pulmonary edema demonstrated with Tl-201 imaging.
AB  - Clinical and scintigraphic findings are described in a patient in whom acute
      right-sided pulmonary edema developed during a treadmill exercise test. The
      patient's SPECT Tl-201 stress images are reviewed along with the pertinent
      clinical history. The development of unilateral pulmonary edema during an
      exercise treadmill test was demonstrated with Tl-201 imaging.

PMID- 11953564
TI  - A new method to measure thyroid uptake with a gamma camera without routine use of
      a standard source.
AB  - PURPOSE: This study was designed to validate a reliable gamma camera-based method
      for measuring thyroid uptake. The method is based on a stable calibration
      procedure and does not require daily use of a standard source. In addition, the
      method is designed to overcome deadtime losses inherent in uptake probe
      measurements with iodine-123. METHODS: A calibration procedure was designed using
      I-123 capsules in a neck phantom and tested using two gamma cameras. Patient
      thyroid uptake measurements made with the proposed gamma camera method were
      correlated with measurements obtained using the traditional uptake probe
      technique. Image quality was compared between the low-energy, parallel-hole
      collimator used in this study and the pinhole collimator usually used for thyroid
      imaging. RESULTS: Capsule count rates measured using the gamma camera are linear
      with activity, and the calibration procedure is reproducible when tests are
      performed several months apart. Thyroid uptake measured with the gamma camera
      correlated closely (R2 > 0.9) with measurements made using the probe technique.
      Image quality with the low-energy parallel-hole collimator was comparable to that
      obtained with the pinhole collimator. CONCLUSIONS: The proposed camera-based
      method for measuring thyroid uptake is accurate and reproducible. It can be
      performed readily in conjunction with the routine scan procedure. Adoption of
      this technique reduces equipment requirements in the nuclear medicine department.

PMID- 11953565
TI  - Detection of small bowel involvement by mantle cell lymphoma on F-18 FDG positron
      emission tomography.
AB  - F-18 fluorodeoxyglucose positron emission tomography (FDG PET) is highly
      sensitive and specific for the detection of nodal and extranodal disease in
      patients with malignant lymphoma. However, no previous reports have shown
      lymphomatous involvement of the small bowel that was recognized on the basis of
      FDG-PET imaging findings. The authors present two cases of clinically unsuspected
      small bowel involvement by mantle cell lymphoma that were initially detected on
      FDG PET.

PMID- 11953566
TI  - New method for calculating right ventricular ejection fraction using gated
      myocardial perfusion studies.
AB  - BACKGROUND: Quantification of right ventricular ejection fraction (RVEF) is
      important in patients who have right heart failure or cor pulmonale. When Tl-201
      was the primary radiotracer used to evaluate myocardial perfusion, the outline of
      the right ventricle could vary and was not visualized in most patients. However,
      visualization of the right ventricle has become easier with the use of Tc-99m
      labeled myocardial perfusion agents. PURPOSE: This study describes a new method
      for quantifying RVEF using gated stress myocardial perfusion (GMP) slices. The
      results are compared with those of first-pass radionuclide ventriculography
      (FPRNA) in the same patients. METHODS: Fifty-two consecutive patients referred
      for routine GMP imaging were included. After administration of Tc-99m
      tetrofosmin, all patients underwent FPRNA using a single crystal gamma camera and
      a GMP study. Regions of interest (ROI) were drawn to outline the right
      ventricular cavity at end diastole and end systole from three pairs of GMP
      slices. The RVEF was calculated from the number of pixels within the ROIs. The
      mean RVEF obtained using FPRNA and GMP imaging was 51.8 +/- 10.8% and 51.9 +/-
      12.3%, respectively. The two methods showed good correlation with r = 0.81. In
      addition, there was no significant difference in the RVEFs calculated using these
      methods (P = 0.85). Bland-Altman analysis also showed good agreement between the
      two methods (limits of agreement +14.4% to -14.0%, slope = 0.19). Intraobserver
      and interobserver correlation were evaluated by reanalyzing 12 patients using the
      new RVEF quantification method and were good at r = 0.87 and 0.82, respectively.
      Therefore, this is a new convenient method for evaluating RVEF as part of a
      routine tomographic gated myocardial perfusion study.

PMID- 11953567
TI  - The value of radionuclide studies in children with autosomal recessive polycystic
      kidney disease.
AB  - PURPOSE: To describe and analyze the appearances of autosomal recessive
      polycystic kidney disease (ARPKD) on Tc-99m DMSA and Tc-99m HIDA scintigraphy.
      MATERIALS AND METHODS: The authors evaluated scintigraphic findings for 13 boys
      and 9 girls (age range, 2 months to 22.75 years; mean, 7.5 years) with ARPKD.
      Fourteen children underwent Tc-99m DMSA and 20 underwent Tc-99m HIDA scintigraphy
      according to European guidelines. Kidney outline, internal structure, tracer
      uptake, and differential function were analyzed on Tc-99m DMSA images, whereas
      relative liver lobe sizes, hepatocyte tracer uptake, time to peak, and excretion
      into the biliary tree and gut were evaluated on Tc-99m HIDA scans. RESULTS: On Tc
      99m DMSA images, loss of kidney outline and internal structure was seen in 75% of
      the scans, and patchy tracer uptake with focal defects throughout the kidneys,
      particularly at the poles, was evident in 93%. In 85% of the cases, the Tc-99m
      DMSA changes did not correlate with the ultrasonographic findings where the
      kidneys are uniformly affected. Characteristic findings on Tc-99m HIDA scans were
      enlarged left liver lobe in 80%, a delay in maximal hepatocyte uptake in 68%,
      delayed tracer excretion into the biliary tree in 32% (with stasis in the
      prominent intrahepatic biliary ducts in 50% or pooling into the segmentally
      dilated biliary ducts in 25%), and delayed excretion into the gut in 40% of
      patients. CONCLUSIONS: In a child with clinically enlarged kidneys that appear
      diffusely hyperechoic on ultrasound, the appearances on Tc-99m DMSA imaging
      strongly support the diagnosis of ARPKD. The Tc-99m HIDA findings, especially of
      an enlarged left lobe of the liver with bile stasis or dilatation, further
      support the diagnosis.

PMID- 11953568
TI  - Genital uptake in renal transplant scintigraphy: is it normal blood pooling?
AB  - Although visualization of the genitalia on Tc-99m DTPA transplant renography has
      been reported previously, its frequency and clinical significance have not been
      fully evaluated. The authors conducted a retrospective evaluation of 153 renal
      transplant scintigrams obtained in 129 patients during a 2-year period. The
      results showed that significant genital blood pooling occurred in nearly 50% of
      studies. Because the finding was commonly associated with little or no
      radioactive urine in the bladder, as in acute tubular necrosis or poor graft
      function, exaggeration of the normal blood pool was thought to be the possible
      cause for its occurrence. It is, however, important to distinguish genital blood
      pool activity from the bladder with radioactive urine to avoid making an
      incorrect diagnosis.

PMID- 11953569
TI  - Scintigraphy of cubital bursitis.
AB  - A 50-year-old man with psoriatic arthropathy was examined for a painful mass in
      the left cubital fossa. The clinical findings indicated a tumor or infection.
      Computed tomographic scanning and bone scintigraphy also raised the possibility
      of a malignant lesion. Surgical exploration revealed that the mass was a
      chronically inflamed bicipitoradial bursa adherent to the biceps tendon. This is
      a rare condition, with only a handful of cases described in the literature. This
      is the first scintigraphic case reported. The imaging features of the bursa are
      discussed in terms of the anatomy.

PMID- 11953570
TI  - Tc-99m MIBI scintigraphy in a patient with primary and metastatic malignant
      melanoma.
AB  - Malignant melanoma is a rare malignant tumor arising within the melanocytes of
      the skin. The authors report a case of primary and metastatic malignant melanoma
      revealed with Tc-99m MIBI in one patient. Tc-99m MIBI images showed uptake in
      possible malignant melanoma skin lesions of the left calf and great toe of a 73
      year-old man. Malignant melanomas (primary and metastatic) were diagnosed on
      excisional biopsies. Tc-99m MIBI scintigraphy might be useful not only in the
      diagnosis of possible primary malignant melanoma lesions but also in the
      diagnosis of metastatic or recurrent disease.

PMID- 11953571
TI  - Localization of extramedullary hematopoiesis with Tc-99m-labeled monoclonal
      antibodies (BW 250/183).
AB  - Extramedullary hematopoiesis is of special interest to physicians because of its
      relation to hematologic disease. Because it normally remains asymptomatic, sites
      are typically found by chance. Effective diagnosis involves a specific, reliable,
      whole-body and low-cost method of screening. Although radiologic methods such as
      computed tomography and magnetic resonance imaging can only suggest the presence
      of extramedullary hematopoiesis, apart from invasive and therefore risky biopsy
      procedures, only scintigraphy can detect and confirm the nature of hematopoietic
      tissue. Although radioactive tracers commonly in use partly lack the demands for
      specific diagnosis, Tc-99m-labeled antibodies (NCA-95) seem to combine the
      advantages of different scintigraphic approaches. Two patients with
      dyserythropoetic anemia and paravertebrally situated pelvic and thoracic tumor
      masses were studied for extramedullary hematopoiesis. Planar and SPECT images
      were obtained 6 and 24 hours after injection of 800 to 850 MBq (22 to 23 mCi) Tc
      99m-labeled monoclonal antibodies (BW 250/183). In both patients, tracer
      accumulated in the masses, thereby revealing hematopoietic tissue. Biopsy
      confirmed these findings. By using Tc-99m-labeled monoclonal antibodies to detect
      extramedullary hematopoiesis, the demands of diagnosis were met. As an
      alternative to invasive diagnostic procedures, this tracer combines the
      advantages of other radioactive substances previously used, such as radioiron, In
      111 chloride, and Tc-99m colloids. This low-cost agent is readily available and
      when applied, reliable, and delivers whole-body images free of additional uptake
      in the liver or spleen.

PMID- 11953572
TI  - Aortojejunal fistula in non-Hodgkin's lymphoma.

PMID- 11953573
TI  - An unusual case of chloroma without marrow involvement demonstrated on Ga-67
      scintigraphy.

PMID- 11953575
TI  - Positive F-18 FDG positron emission tomography in the perineum after anorectal
      reconstruction.

PMID- 11953574
TI  - Scintigraphy of an avulsion injury of the sartorius insertion in the pelvis.

PMID- 11953576
TI  - Bone densitometry study in a patient with prior kyphoplasty variant of
      vertebroplasty.

PMID- 11953577
TI  - False-negative interpretation of FDG positron emission tomography in a patient
      with Hodgkin's lymphoma.

PMID- 11953578
TI  - Hibernoma: intense uptake seen on Tc-99m tetrofosmin and FDG positron emission
      tomographic scanning.

PMID- 11953579
TI  - A case of malignant lymphoma with breast and ovary involvement as a cause of
      fever of unknown origin detected by Ga-67 scintigraphy.

PMID- 11953580
TI  - Discordant Tc-99m depreotide and F-18 FDG imaging in a patient with poorly
      differentiated small-cell neuroendocrine carcinoma.

PMID- 11953581
TI  - Intense F-18 FDG accumulation in the stomach in a patient with Menetrier's
      disease.

PMID- 11953582
TI  - Bilateral adrenal metastases revealed by F-18 FDG coincidence detection positron
      emission tomography in a patient with lung cancer.

PMID- 11953583
TI  - Cutaneous metastasis revealing a widely disseminated follicular thyroid
      carcinoma.

PMID- 11953584
TI  - Tc-99m MIBI filling pattern in a photopenic area of a Tc-99m MDP scan in a
      patient with metastatic bone involvement of breast carcinoma.

PMID- 11953585
TI  - Lymphoscintigraphic evaluation of congenital lymphedema of the newborn.

PMID- 11953586
TI  - Tl-201 imaging in the diagnostic work-up of squamous cell carcinoma metastasis of
      unknown primary origin.

PMID- 11953587
TI  - Current readings in nuclear medicine.

PMID- 11953589
TI  - Local resection of malignant lesions of the hip and pelvis. 1966.

PMID- 11953590
TI  - Combined posterior pelvis and lumbar spine resection for sarcoma.
AB  - The oncologic outcome in the treatment of pelvic sarcomas is not comparable with
      that in the extremity. Particular problems arise when the tumor involves the
      posterior pelvis and the sacrum or even the lower lumbar spine. Because of the
      difficulty in achieving local control and the major functional deficits after
      extensive surgery, some authors suggest conservative, nonsurgical treatment for
      these patients. The purpose of the current study was to analyze the oncologic
      outcome of patients who were treated for a pelvic sarcoma necessitating resection
      of the ilium, part of the sacrum and part of the lower spine, which is defined as
      extended hemipelvectomy. Between 1979 and 1999, 11 males and seven females with a
      mean age of 34.5 years (range, 14-67 years) had an extended hemipelvectomy for a
      sarcoma of the posterior pelvis. The tumors included seven osteogenic sarcomas,
      six chondrosarcomas, and five fibrosarcomas: 13 were classified as high-grade
      lesions. The mean size of the tumor was 11 x 9 x 6 cm. In 11 patients, a
      hemivertebrectomy of L5 and in seven patients of L4 combined with L5 was done to
      achieve an adequate margin. In four patients, the resection was followed by
      reconstruction with a vascularized fibula or autograft. At a mean followup of 56
      months (range, 3-220 months), 12 of 18 patients were alive and without disease.
      Six patients died; four of these patients had metastasis to the lung at
      presentation. The two remaining patients died of complications of adjuvant
      treatment. The authors conclude from this small series of patients that an
      aggressive surgical resection for localized, nonmetastatic, high-grade sarcomas
      of the posterior pelvis may be justified to provide local control and improve
      survival.

PMID- 11953591
TI  - Treatment and outcome of recurrent pelvic chondrosarcoma.
AB  - Little has been published about the outcome of patients with recurrent
      chondrosarcoma of the pelvis. The current study is a review of patients with
      surgically treated locally recurrent pelvic chondrosarcoma at one institution.
      Twenty-one patients had surgical resection of recurrent pelvic chondrosarcoma
      between July 1974 and July 1996. There were nine women and 12 men with a mean age
      of 46 years (range, 24-67 years) at first recurrence. Patients were followed up
      for a minimum of 3.3 years and median of 12 years from first (index) recurrence
      or until death. The mean time to index recurrence was 27 months (range, 5-87
      months). In three cases (14%), the tumor at index recurrence was a higher grade
      than the initial lesion. There were six additional tumors that became a higher
      grade during subsequent recurrences. Fifteen of the 21 patients (71%) had a
      second local recurrence. Five patients (24%) had distant metastasis. At death or
      final followup, 11 patients (52%) had no evidence of disease, two patients (10%)
      are alive with disease, and eight patients (38%) died of their disease. The three
      patients with high-grade tumors at index recurrence all died of disease. The
      treatment of recurrent pelvic chondrosarcoma is a challenging problem. Tumor-free
      margins may require radical surgery, and the best chance of cure is at the time
      of initial resection. With aggressive surgical intervention, approximately 50% of
      patients with recurrent pelvic chondrosarcoma can achieve long-term survival.

PMID- 11953592
TI  - Iliofemoral arthrodesis and pseudarthrosis: a long-term functional outcome
      evaluation.
AB  - Reconstruction after the resection of pelvic tumors is a major challenge. It
      depends on many factors such as age, activity level, type of tumor, its adjuvant
      treatment, and the extent of the disease. The purpose of the current study was to
      analyze the functional and oncologic outcomes of patients who had an iliofemoral
      arthrodesis after resection of a pelvic sarcoma. Between 1981 and 1999, 20 males
      and 12 females with a mean age of 39.9 years (range, 10-71 years) had an
      iliofemoral arthrodesis, either as a solid fusion or primary pseudarthrosis, at
      one institution. The functional outcome was evaluated using the Musculoskeletal
      Tumor Society and the Toronto Extremity Salvage scores. At a mean followup of 97
      months (range, 14-226 months), 15 of 32 patients were alive, all without disease.
      The radiographic union rate was 86%. The mean overall Musculoskeletal Tumor
      Society and Toronto Extremity Salvage scores were 64% and 48%, respectively.
      Patients with a primary solid fusion did functionally better compared with
      patients who had pseudarthrosis (Toronto Extremity Salvage Score, 76%;
      Musculoskeletal Tumor Society Score, 71% versus Toronto Extremity Salvage Score,
      52%; Musculoskeletal Tumor Society Score, 25%). Biomechanical analysis showed
      that the loss of motion in the hip is well-compensated. The authors conclude from
      this series that iliofemoral reconstruction after resection of a pelvic sarcoma
      provides acceptable and durable long-term results, not only from the oncologic,
      but also from the functional perspective.

PMID- 11953593
TI  - Bowel and bladder function after major sacral resection.
AB  - Major sacral resection generally is reserved for patients with malignant lesions.
      Because of the uncommon nature of these diseases, little is known about outcomes
      of surgical treatment. The current authors describe the retrospective analysis of
      bowel and bladder function in patients having major sacral resection at their
      institution during a 10-year period. Fifty-three patients were identified. In
      patients who had unilateral sacrectomy, in whom the contralateral sacral nerves
      were preserved, normal bowel and bladder function was retained in 87% and 89%,
      respectively. In patients who had bilateral S2-S5 nerve roots sacrificed, all had
      abnormal bowel and bladder function. In patients who had bilateral S3-S5
      resection, normal bowel and bladder function was retained in 40% and 25%,
      respectively. In patients who had bilateral S4-S5 resection, with preservation of
      the S3 nerves bilaterally, normal bowel and bladder function was retained in 100%
      and 69%, respectively. In patients who had asymmetric sacral resections, with
      preservation of at least one S3 nerve root, normal bowel and bladder function was
      retained in 67% and 60%, respectively. These results show that unilateral
      resection of sacral roots or preservation of at least one S3 root in bilateral
      resection preserves bowel and bladder function in the majority of patients.

PMID- 11953594
TI  - Etiology of osteosarcoma.
AB  - Although the prognosis and quality of life of patients with osteosarcoma were
      improved significantly during the past decades, the pathogenesis and etiology of
      this disease remain obscure. Significant interest and effort in this cancer led
      to the identification of numerous etiologic agents. Several chemical agents such
      as beryllium, viruses such as FBJ, subsequently found to contain the src
      oncogene, and radiation were shown to be potent inducers of osteosarcoma. Paget's
      disease, electrical burn, or trauma all are thought to be other factors that may
      contribute to the pathogenesis. More recently, patients with hereditary diseases
      such as Rothmund-Thomson syndrome, Bloom syndrome, and Li-Fraumeni syndrome were
      found to have an increased risk of having osteosarcoma develop. During the past
      few years, the molecular analysis brought a wealth of new information with
      numerous genes that were associated with osteosarcoma and its clinical disease
      progression. They can be categorized into self-sufficiency in growth signals,
      insensitivity to growth inhibitory signals, evasion of apoptosis, limitless
      replicative potential, sustained angiogenesis, and tissue evasion and metastasis.
      Although the understanding of these processes in osteosarcoma still is
      incomplete, it may have the potential to significantly affect the patient care in
      the future.

PMID- 11953595
TI  - Primary osteosarcoma in adults older than 40 years.
AB  - The aim of the current study was to determine the prognostic factors of primary
      osteosarcoma in adults. This is a review of 47 patients older than 40 years (27
      men and 20 women) who were treated between 1977 and 1998 at the authors'
      institution. Tumors involved the lower limbs in 26 patients and the axial
      skeleton in 18 patients (38.3%). Eight patients (17%) had synchronous pulmonary
      metastasis and seven had a pathologic fracture before the definitive surgery. At
      review, 33 patients had died and 13 were alive. Twenty-one patients (44.7%) did
      not receive any form of systemic treatment. Tumors were treated surgically in 42
      patients (89%). Local recurrence was documented in seven patients (17%).
      Metastasis after diagnosis appeared in 29 patients (61.7%). The 5-year disease
      free survival and overall survival rates were 32.54% and 41.64%, respectively.
      Adult patients (> 19 years) with primary osteosarcoma had a poor clinical
      outcome. Metastatic disease at presentation or later, a pathologic fracture,
      large tumor volumes, and inadequate margins at the time of surgery were
      associated with significantly lower survival. The high number of adults
      presenting with advanced stage lesions and more tumors in the axial location
      might explain the high rate of recurrences. Aggressive multiagent regimens are
      needed to improve survival.

PMID- 11953596
TI  - Angiogenic cytokines in cartilage tumors.
AB  - Pathologic neovascularization has been described in numerous types of cancers.
      The angiogenic cytokines vascular endothelial growth factor and basic fibroblast
      growth factor are thought to be the primary inducers of angiogenesis in these
      tumors. Hypoxia-inducible transcription factor is a nuclear transcription factor
      that promotes vascular endothelial growth factor expression. Prior studies have
      shown pathologic neovascularization in chondrosarcoma, which correlates with
      pathologic grade of the tumor. Angiogenic and nonangiogenic cartilage tumors were
      studied for expression of vascular endothelial growth factor, basic fibroblast
      growth factor and hypoxia-inducible transcription factors by immunohistochemistry
      and Northern blot analysis. Expression of vascular endothelial growth factor and
      hypoxia-inducible transcription factor were increased significantly in angiogenic
      tumors. Fibroblast growth factor expression was similar in angiogenic and
      nonangiogenic specimens. This may have implications for tumor grading and
      surgical decision-making, and potential treatment with antiangiogenesis
      chemotherapeutic agents.

PMID- 11953597
TI  - Galectin-3: a biologic marker and diagnostic aid for chordoma.
AB  - Galectin-3 is a beta-galactoside binding protein. Its expression is
      quantitatively and qualitatively altered during self-proliferation, malignant
      transformation, and tumor progression. Galectin-3 is a lectin-related molecule.
      Lectins are proteins that bind specific carbohydrate structures. Although their
      precise biologic function is unclear, the general idea is that these molecules
      operate in modulating cell-to-cell and cell-to-matrix interactions. Galectins
      have been implicated in cell growth and differentiation and seem to play a role
      in malignant transformation and metastasis. Galectin-3 is expressed in primitive
      notochord. The purpose of the current investigation was to identify an
      immunohistochemical marker to help distinguish the pathologically overlapping
      entities of chordoma from myxoid low-grade chondrosarcoma. Twelve of 16 (75%)
      chordomas stained positive for Galectin-3 whereas only one of 12 low-grade myxoid
      chondrosarcomas stained positive. Galectin-3 chordoma staining is 75% sensitive
      and 92% specific.

PMID- 11953598
TI  - Pathologic neovascularization in cartilage tumors.
AB  - Tumor-induced angiogenesis is necessary to sustain radial growth of tumors.
      Increased microvascularity has been correlated with increased metastatic
      potential in breast, gastrointestinal, and gynecologic tumors, but has not been
      well studied in cartilaginous tumors. Grade II and Grade III chondrosarcomas have
      increased metastatic potential compared with Grade I tumors. One reason for this
      may be pathologic neovascularization. The purpose of the current study was to
      quantify the microvessel density of cartilage tumors. Seven Grade III, 17 Grade
      II, and eight Grade I chondrosarcomas, and 22 benign cartilage tumors were
      examined. Specimens were stained with antiCD34 antibody. Microvessel densities
      then were determined by direct counting and estimated using the Chalkley
      technique. Microvessel densities for Grade III and Grade II chondrosarcomas were
      45.9 and 46.2 per high-power field and for Grade I and benign tumors the
      microvessel densities were 9.3 and 10.3. Microvessel densities of the aggressive
      tumors (Grades III and II) were greater than the microvessel densities of the
      nonaggressive tumors (Grade I and benign). Chalkley estimates confirmed the
      results. Microvascularity in cartilage tumors correlates with their biologic
      aggressiveness and seems promising as a variable to help with histopathologic
      grading and as a target for new treatment modalities.

PMID- 11953599
TI  - Prereferral evaluation of patients with suspected bone and soft tissue tumors.
AB  - One hundred consecutive patients referred to an orthopaedic oncology practice for
      evaluation of suspected bone or soft tissue tumors were studied prospectively.
      There were 76 patients with bone lesions and 24 patients with soft tissue
      lesions. At the time of initial consultation, information regarding the referring
      diagnosis, number of prior physician office visits, and prereferral imaging
      studies obtained was collected. There were 50 patients with benign tumors, 17
      patients with primary malignant tumors, 11 patients with metastatic tumors, and
      22 patients with nonneoplastic conditions. The average number of physician visits
      before referral for the entire group was 4.8 visits and was highest for patients
      with malignant bone tumors (6.2 visits). Imaging studies obtained before referral
      included plain radiographs, magnetic resonance imaging, bone scans, computed
      tomography scans, and ultrasound. None of the plain radiographs were thought to
      be unnecessary; however, 26 of 76 (34.2%) magnetic resonance imaging scans, 17 of
      40 (42.5%) bone scans, and 13 of 36 (36.1%) computed tomography scans were
      excessive and did not contribute to the evaluation of the lesion. Although only
      58% of the study group included patients with benign bone tumors and
      nonneoplastic bone lesions, they accounted for the majority (79%) of unnecessary
      imaging studies. Primary care physicians and general orthopaedic physicians were
      equally likely to order unnecessary imaging studies (48% and 52%, respectively).

PMID- 11953600
TI  - The effect of contaminated surgical margins revisited.
AB  - The current study was done to assess the oncologic outcomes after inadvertent
      intraoperative contamination in the treatment of musculoskeletal sarcomas, to
      determine the prognostic significance of these events. Forty-three patients with
      malignant lesions and either positive margins or intraoperative tumor penetration
      are included in the study. There were 12 bone lesions and 31 soft tissue lesions.
      The final margin was intracapsular in 11 patients, contaminated marginal in 13
      patients, and contaminated wide in 19 patients. Thirty-two patients received
      radiation therapy with doses from 4560 to 7000 cGy. The mean followup was 69
      months (range, 24-179 months). In patients in whom the surgical margin was
      contaminated, additional tissue was removed with the goal being to obtain tumor
      free surgical margins. Local recurrence occurred in four of 32 patients (12.5%)
      with no gross residual tumor. There was a significant difference in the
      recurrence rate between a wide (0 of 19) versus a marginal or intracapsular
      margin (nine of 24) based on the final surgical margin. High-grade lesions were
      more likely to recur than low-grade lesions, and soft tissue lesions were more
      likely to recur than bone lesions. Similar to previous reports, treatment of
      inadvertent contamination with reexcision and irrigation of the wound results in
      a similar recurrence rate to cases without contamination. Efforts should be made
      to achieve a wide final margin. Adjuvant therapies should be used whenever
      feasible.

PMID- 11953601
TI  - The use of flow cytometry in assessing malignancy in bone and soft tissue tumors.
AB  - Since 1982, the orthopaedic research laboratories at the authors' hospital has
      done flow cytometric and more recently cytofluorometric deoxyribonucleic ploidic
      analyses of samples of bone and soft tissue tumors. The current authors attempt
      to define the value of such studies in distinguishing benign from malignant
      tumors, in conforming to stage of the tumors, and in helping to predict
      metastasis and death. The series consists of 1134 patients in whom the disease
      was verified and the survival data were available as a result of a questionnaire
      study. Statistically, the ploidic analyses were of remarkable value in defining
      malignancy and in correlating with the stage of the lesion. They were of less
      value in predicting survival, particularly for patients with osteosarcoma and
      chondrosarcoma, but seemed to predict survival effectively for patients with soft
      tissue sarcomas.

PMID- 11953602
TI  - Long-term followup of proximal femoral allografts.
AB  - Between 1972 and 1999, the orthopaedic service at the authors' institution
      treated 137 patients with proximal femoral bone lesions by resection and
      reconstruction with frozen allografts from cadavers. The data were entered into a
      computer program allowing a comprehensive analysis. Thirty-eight patients had
      proximal femoral osteoarticular allografts, 69 had allograft-endoprosthesis
      composites, 22 had intercalary allografts, and eight had an allograft
      arthrodesis. There were 74 complications in 54 of the 137 patients with
      allografts, which included 26 allograft fractures (19%), 15 infections (11%), and
      20 nonunions (15%). The overall success rate for the patients with these
      procedures was 103 of 137 (75%) at a mean followup of 7.9 years +/- 5.6 years. If
      the eight patients with tumor recurrences (surgical failures rather than
      allograft failures) are not included, the success rate is 103 of 129 (80%).
      Eighty-three of these patients (55%) without any allograft complications who have
      been treated and followed up for at least 2 years had a 92% success rate. It is
      concluded that although allograft reconstruction after resection of the proximal
      femur for patients with aggressive or malignant tumors has a high complication
      rate, approximately 80% of the patients have a successful outcome.

PMID- 11953603
TI  - Revision of the failed distal femoral replacement to allograft prosthetic
      composite.
AB  - Orthopaedic oncologists often prefer a modular prosthetic cemented prosthesis for
      reconstruction after tumor excision in the distal femur. However, these
      frequently young patients face the prospect of either mechanical failure or
      loosening during their lifetime. Between 1993 and 2000, 41 patients (18 males, 23
      females) with a malignancy of the distal femur had distal femoral replacement.
      Eight revisions and one amputation were required. Of these, four patients had
      revision to an allograft-prosthetic composite because of prosthetic fracture or
      loosening. These patients comprise the study population. Revisions were required
      at an average of 4 years after distal femoral replacement and the average age of
      the patients at revision was 17 years. The average time to achieve healing at the
      allograft-host junction was approximately 3 months and patients were fully
      weightbearing by that time. Followup from revision surgery to the last visit
      averaged 59 months, with average Musculoskeletal Tumor Society and Hospital for
      Special Surgery scores of 62% and 72%, respectively. There have been no
      mechanical problems, fractures, or osteolysis to signify loosening in the
      allograft or host bone. It is anticipated that this type of revision will survive
      longer than a conventional cemented revision and obviate the need for multiple
      reoperations in young patients who have difficulty with the biologic features of
      a cemented prosthesis construct.

PMID- 11953604
TI  - Repair of bone allograft fracture using bone morphogenetic protein-2.
AB  - Long-term clinical data have shown that reconstruction using bone allografts
      provide adequate function after extensive tumor surgery. Complications such as
      nonunion of allograft-host interface, infection, and allograft fracture often
      require major revision surgeries. Allograft fractures usually do not induce the
      same repair process that is seen in normal fracture healing. The authors did an
      experimental study to test whether bone morphogenetic protein-2 can induce and
      achieve osseous repair in an allograft osteotomy model. Recombinant human bone
      morphogenetic protein-2 was applied at femoral intercalary allograft osteotomy
      sites in 20 rats. Forty additional rats served as controls (carrier alone and
      sham). Specimens in all groups were examined histologically and radiographically
      at 4 and 8 weeks. Specimens in the control groups showed only fibrosis by 8
      weeks. In contrast, none of 10 specimens in the experimental group showed
      radiographic union at 8 weeks. New bone formation and integration with underlying
      allografts were seen in the experimental group as early as 4 weeks. These data
      suggest that fracture repair in the allograft bone can be triggered by a biologic
      regulator that is expressed during normal fracture healing.

PMID- 11953605
TI  - Relationship between surgical margins and local recurrence in sarcomas of the
      spine.
AB  - The combination of improved resection, stabilization, and fusion techniques
      allows for more aggressive removal of malignant spinal tumors with acceptable
      mortality and morbidity. Thirty consecutive patients with primary sarcomas of the
      mobile spine, who were operated on at the authors' institution from January 1970
      to December 2000, were included in the current study. Demographic information,
      tumor location, type of resection, resection margins, local recurrence, and
      overall survival data were retrieved and analyzed. Treatment consisted of en bloc
      resection in 12 patients (40%) and piecemeal resections in 18 patients (60%). The
      resection was classified as wide in seven patients (23.3%), marginal in three
      patients (10%), and intralesional in 20 patients (66.7%). Pathology reports
      showed tumor-free resection margins in 12 patients (40%). In the remaining 18
      patients (60%), resection margins were positive and resulted in a fivefold
      increase in the risk of a local recurrence. Ninety-two percent of the patients
      with local recurrence died of sequelae associated with the local recurrence.
      Primary sarcomas of the mobile spine in certain cases, can be removed completely
      with tumor-free resection margins. En bloc resection with tumor-free margins
      provides substantial improvement in overall survival.

PMID- 11953606
TI  - Shoulder reconstruction after tumor resection by pedicled scapular crest graft.
AB  - The current authors present and evaluate a technique for reconstructing proximal
      humeral defects that result after resection of malignant bone tumors. Sixteen
      patients were included in this study with an average followup of 3 years (range,
      12-76 months). Twelve patients had intraarticular resections, two had
      extraarticular resections, and two had intercalary resections. Reconstruction was
      done at the lateral border of the scapula (based on the circumflex scapular
      vessels) that was osteotomized and mobilized to bridge the resultant defect.
      Shoulder arthrodesis was done in 14 patients and the shoulder was spared in the
      two patients who had intercalary resections. Function was evaluated according to
      the Musculoskeletal Tumor Society scoring system. The average time for union of
      the graft proximally and distally was 6 months after which the graft started to
      hypertrophy. The average functional score was 22.5 points (75%) with a minimum
      score of 18 points (60%) and a maximum score of 27 points (90%). Nonunion of the
      distal host-graft junction occurred in two patients; both patients required iliac
      crest bone grafting and both achieved clinical and radiographic union without
      additional intervention. In three patients, the proximal fixation became loose
      but had no effect on function. The authors conclude that this technique is
      inexpensive, effective, and a durable reconstructive option for proximal humeral
      defects that are less than 15 cm. It has a predictable functional outcome (60%
      90%) that is comparable with other reconstructive options.

PMID- 11953607
TI  - Constrained total scapula reconstruction after resection of a high-grade sarcoma.
AB  - Patients with high-grade sarcomas arising from the scapula or periscapular soft
      tissues traditionally have been treated with either a total scapulectomy or a
      wide, en bloc, extraarticular scapular resection, termed the Tikhoff-Linberg
      resection. The major challenge after such resections is to restore shoulder
      girdle stability while preserving a functional hand and elbow. The current
      authors describe three patients who had an extraarticular, total scapula
      resection (modified Tikhoff-Linberg) for a high-grade sarcoma. Each patient had
      reconstruction with a constrained (rotator cuff-substituting) total scapula
      prosthesis in an effort to optimally restore the normal muscle force couples of
      both glenohumeral and scapulothoracic mechanisms. At latest followup, the
      Musculoskeletal Tumor Society functional score was 24 to 27 of 30 (80%-90%). All
      patients had a stable, painless shoulder and functional hand and elbow. Forward
      flexion and abduction ranged from 25 degrees to 40 degrees. Glenohumeral rotation
      (internal rotation, T6; external rotation -10 degrees) below shoulder level,
      shoulder extension, and adduction were preserved. Protraction, retraction,
      elevation, and abduction of the scapula were restored and contributed to shoulder
      motion and upper extremity stabilization. There were no complications. Total
      scapula reconstruction with a constrained total scapula prosthesis is a safe and
      reliable method for reconstructing the shoulder girdle after resection of select
      high-grade sarcomas. The authors emphasize the clinical indications, prosthetic
      design, surgical technique, and early functional results.

PMID- 11953608
TI  - Osteosarcoma of the proximal humerus: long-term results with limb-sparing
      surgery.
AB  - The purpose of the current study was to analyze the long-term oncologic and
      functional results and complications associated with limb-sparing surgery and
      endoprosthetic reconstruction for 23 patients with osteosarcoma of the proximal
      humerus. There was one Stage IIA lesion, 18 Stage IIB lesions, and four Stage III
      lesions in this study group. Twenty-two patients were treated with an
      extraarticular resection that included the deltoid and rotator cuff and one
      patient was treated with an intraarticular resection that spared the shoulder
      abductors. In all these patients, the proximal humerus was reconstructed with a
      cemented endoprosthetic replacement that was stabilized via a technique of static
      suspension (Dacron tapes) and dynamic suspension (muscle transfers). At latest
      followup (median, 10 years), 15 patients (65%) were alive without evidence of
      disease. There were no local recurrences. Prosthetic survival was 100% for the 15
      survivors. The Musculoskeletal Tumor Society upper extremity functional score
      ranged from 24 to 27 (80%-90%). All shoulders were stable and pain-free. Elbow
      and hand function were preserved in all patients. The most common complication
      was a transient neurapraxia (n = 8). En bloc extraarticular resection and
      endoprosthetic reconstruction is a safe and reliable method of limb-sparing
      surgery for patients with high-grade extracompartmental osteosarcoma of the
      proximal humerus.

PMID- 11953609
TI  - Preoperative radiotherapy in the treatment of soft tissue sarcomas.
AB  - The goal of the current study was to analyze the oncologic results and wound
      complications in patients with soft tissue sarcomas treated with preoperative
      radiation therapy and en bloc resection. A standard protocol of preoperative
      radiotherapy was administered followed by en bloc resection in 209 patients. The
      protocol included needle or incisional biopsy, prospective staging, a consistent
      dose of radiotherapy, standardized prospective evaluation of surgical margins,
      and long-term followup. The target radiotherapy dose was 50.4 cGy. Twenty-nine
      patients had low-grade lesions, and 180 had high-grade lesions. The mean followup
      was 55 months. The significant wound complication rate was 22% (moderate 14%,
      major 7%, and amputation 1%). Wound complications were significantly higher in
      patients with lower extremity lesions when compared with patients with upper
      extremity or axial lesions, and in patients with lesions larger than 5 cm. The
      local recurrence rate was 11% in patients who did not have prior surgery, and 37%
      in patients who had prior surgery at an outside institution (17% overall). Local
      recurrence was increased significantly in patients who had prior surgery. At
      latest followup, 78 patients (47%) were continuously disease-free, six (4%) were
      alive with no evidence of disease, nine (5%) were alive with disease, 63 (38%)
      died of disease, and 11 (7%) died of another cause. The 2- and 5-year disease
      specific survival rates were 77% and 67%, respectively. Overall survival was 56%.
      A significant decrease in survival was seen in patients who had a local
      recurrence, and in patients with high-grade lesions. Preoperative radiotherapy
      can be given safely with a wound complication rate not significantly higher than
      that reported for other forms of radiotherapy delivery. Local recurrence tends to
      be higher if surgical intervention is done before tertiary center referral.
      Distant disease continues to be the cause of the high mortality in these
      patients.

PMID- 11953610
TI  - Radiation therapy for low-grade soft tissue sarcoma.
AB  - One hundred eight patients with low-grade soft tissue sarcoma treated at the
      authors' institution from 1984 to 1999 were reviewed retrospectively. Low-grade
      sarcomas were defined as those designated as Grade I of III or Grade I or II of
      IV. Patients who presented with recurrent tumors or who had multiple procedures
      at outside institutions were excluded. The patient's gender, age at diagnosis,
      histologic diagnosis, site and depth of primary involvement, and specimen size at
      resection were noted. Involvement of periosteum, bone, and neurovascular
      structures also was recorded. The decision to use radiation therapy was made case
      by-case. Indications for preoperative radiation therapy included tumor adjacent
      to the neurovascular bundle or bone where a marginal surgical margin was
      anticipated. Indications for postoperative radiation therapy included followup
      resection of an unsuspected malignancy. Patients were evaluated according to
      treatment rendered. Sixty-six patients were treated with surgery alone, whereas
      42 patients had excision of the tumor in conjunction with radiation therapy. The
      overall local control rate was 97.2% (105 of 108). There were no statistically
      significant differences in local recurrence, wound complication, fibrosis, or
      survival between the two groups. Patients treated with radiation therapy had an
      increased incidence of postoperative lymphedema. Kaplan-Meier 10-year survival
      rates were approximately 90% for both groups.

PMID- 11953611
TI  - Karnofsky performance score as a predictor of survival in soft tissue sarcoma.
AB  - Forty-six consecutive patients with nonmetastatic, large, high-grade soft tissue
      sarcomas were treated with surgical resection and radiation therapy but no
      adjuvant chemotherapy. Clinical and radiographic followup ranged from 36 to 90
      months (mean, 50 months). One patient died of unrelated causes 10 months after
      the completion of radiation and surgery, leaving the oncologic outcome of 45
      patients to be evaluated. Twenty-seven of 45 patients (60%) survived with an
      average followup of 50 months. The limb salvage rate was 91% and local control
      was obtained in 43 of 45 patients (96%). During the time of the study, 73% of
      patients could have been offered chemotherapy. However, only 53% of patients who
      died of their disease would have been candidates for chemotherapy trials because
      of medical comorbidities. More importantly, patients with a Karnofsky performance
      score of 80 or more had a significantly better survival rate than patients with a
      Karnofsky performance score less than 80 without the use of chemotherapy. Current
      chemotherapy trials that exclude patients because of medical comorbidities are
      introducing bias toward improved survival that may not be attributable to the
      chemotherapy. If a real survival benefit of adjuvant chemotherapy exists, it
      would be most evident in the largest (> 15 cm) high-grade tumors. Aggressive
      metastasectomy seems to be most beneficial for patients with isolated nodules.

PMID- 11953612
TI  - Magnetic resonance imaging after incomplete resection of soft tissue sarcoma.
AB  - Review of magnetic resonance imaging was compared with the pathologic review of
      reexcision specimens from 24 pediatric patients who had initial incomplete
      resection for soft tissue sarcoma to determine the accuracy of magnetic resonance
      imaging in detecting residual tumor. The median age of patients was 12.8 years.
      The most common diagnosis was synovial sarcoma (eight of 24 patients; 30%).
      Magnetic resonance imaging detected residual tumor in eight patients and no tumor
      in eight patients; the images of eight patients were indeterminate. Pathologic
      examination showed residual tumor in 14 of 24 (58%) specimens obtained in
      reexcision. For two of the eight patients (25%) for whom imaging had detected no
      tumor, microscopic examination detected residual tumor; for one of the eight
      patients for whom imaging had detected tumor, microscopic examination detected no
      tumor. Five of the eight patients (63%) for whom the results of imaging studies
      were indeterminate had residual tumor on microscopic evaluation. The sensitivity
      of magnetic resonance imaging for detecting residual tumor was 78%, the
      specificity was 86%, the positive predictive value was 0.78, and the negative
      predictive value was 0.86. Decisions regarding the need for additional resection
      should not be based on magnetic resonance imaging alone.

PMID- 11953613
TI  - Fast magnetic resonance imaging with contrast for soft tissue sarcoma viability.
AB  - Because dynamic (fast) contrast-enhanced magnetic resonance imaging with its
      temporal resolution allows evaluation of contrast kinetics of soft tissue
      sarcomas, its efficacy for defining viable tumor in these neoplasms was studied
      for three applications: biopsy localization, chemotherapeutic response, and
      differentiation between recurrence and inflammation after treatment. After
      conventional T1-weighted and T2-weighted magnetic resonance sequences to localize
      the lesion, patients had dynamic contrast-enhanced magnetic resonance imaging
      with fast and ultrafast sequences and postprocessing techniques (subtraction,
      time-intensity curves, and parametric color-encoding). In 10 of 40 patients,
      dynamic imaging more precisely defined the most malignant foci of tumor for
      biopsy than conventional magnetic resonance imaging. After chemotherapy, dynamic
      imaging distinguished 11 good responders from 21 poor responders. In followup of
      196 patients, dynamic imaging detected 42 early enhancing recurrences and
      excluded recurrent tumor in six late enhancing pseudotumors. Dynamic imaging can
      differentiate viable tumor from nonviable tumor and inflammation by showing two
      temporally different phases of contrast enhancement: an early phase correlative
      with viable tumor at histologic examination, and a late phase when all tissues
      enhance simultaneously and may be indistinguishable. By showing tumor viability,
      dynamic contrast-enhanced magnetic resonance imaging can help define biopsy
      sites, chemotherapeutic response, and presence or absence of recurrences and
      therefore affect the initial evaluation, treatment, and followup of patients with
      soft tissue sarcomas.

PMID- 11953614
TI  - Synergism of aminobisphosphonates and farnesyl transferase inhibitors on tumor
      metastasis.
AB  - Aminobisphosphonates have shown significant antitumor activity in vitro and in
      vivo with selective pharmacodistribution to bone, and an established role in the
      treatment of malignant bone disease. Given that the mode of action of
      aminobisphosphonates involves decreasing the prenylation of the Rho family of
      proteins, through decreasing the availability of prenyl groups (farnesyl and
      geranylgeranyl isoprenoids), the authors sought the inhibition of Rho protein
      prenylation at two points, by using an aminobiphosphonate (alendronate) in
      conjunction with a prenyl transferase inhibitor (R115777, a specific farnesyl
      transferase inhibitor with limited effects in geranylgeranyl transferase). The
      authors show synergistic inhibition of the prenylation dependent membrane
      association and migratory function of Rho proteins, translating into a
      suppressive effect on in vitro tumor cell invasiveness and in vivo metastasis.
      The findings support the use of aminobisphosphonates in conjunction with farnesyl
      transferase inhibitors in the prevention of metastatic progression and suggest
      that metastatic progression is a valid end point in assessing the antitumor
      activity of farnesyl transferase inhibitors.

PMID- 11953615
TI  - Results of treatment for metastatic osteosarcoma with neoadjuvant chemotherapy
      and surgery.
AB  - The purpose of the current study was to define the survival outcome variables for
      the 85 patients with Stage IIB osteosarcoma treated with neoadjuvant chemotherapy
      at the authors' institution from 1982 to 1997. A minimum 4-year followup or death
      was a requisite for inclusion. Forty-three patients were relapse-free survivors
      and 14 had no evidence of disease at followup for an overall survival of 67%.
      Twenty-nine patients had thoracotomy and nine have no evidence of disease with a
      minimum 4-year followup from last thoracotomy. The mean time to metastasis after
      diagnosis for patients presenting with Stage IIB disease was 12.8 months. There
      was no difference in the survival for any of the three chemotherapy protocols,
      used during the 15 years included in this analysis. There was a significant
      relation between length of time to relapse and survival. For each additional year
      without relapse, there is an 18% increase in chance of survival. In patients who
      were treated with thoracotomy, the number of metastatic nodules was a significant
      predictor of survival; specifically, each nodule increased the risk of death by
      43%. A favorable outcome in this cohort of patients is related to the length of
      time between initiation of therapy and diagnosis of metastasis, and the number of
      metastatic foci.

PMID- 11953616
TI  - Giant cell tumor of long bone: a Canadian Sarcoma Group study.
AB  - A multicentric retrospective study of giant cell tumor of bone was conducted
      among Canadian surgeons. The hypothesis was that no differences would be found in
      health status, function, or recurrence rate irrespective to the nature of filling
      material or adjuvant used in patients treated with curettage. One hundred eighty
      six cases were collected. There were 96 females and 90 males. The mean age of the
      patients was 36 years (range, 14-72 years), the minimum followup was 24 months,
      and the median followup was 60 months. Sixty-two percent of the tumors involved
      the knee region. One hundred fifty-eight were primary tumors and 28 were
      recurrences. Campanacci grading was as follows: Grade 1, seven patients; Grade 2,
      100 patients; Grade 3, 76 patients; and unknown in three patients. Fifty-six
      patients had a pathologic fracture. Resection was done in 38 patients and 148
      patients had curettage. The latter was supplemented with high speed burring in
      135 patients, cement in 64 patients, various combinations of autograft or
      allograft bone in 61 patients, phenol in 37 patients, and liquid nitrogen in 10
      patients. Structural allografts were used in 25 patients. The overall recurrence
      rate was 17%, 18% after curettage, and 16% after resection. Patients with primary
      tumors treated with curettage had a 10% recurrence rate. For recurrent lesions
      treated by curettage, the recurrence rate was 35%. The nature of the filling
      material used or the type of adjuvant method used or any combination of both
      failed to show any statistical impact on the recurrence risk. The results from
      the Musculoskeletal Tumor Society rating from 1987 were significantly lower in
      patients who sustained a displaced fracture. Results from the bodily pain section
      of the Short Form-36 also were found to be lower when a pathologic fracture was
      present. Results from the Musculoskeletal Tumor Society Rating 1987, the Short
      Form-36, and the Toronto Extremity Salvage Score did not show differences when
      either cement or bone graft were used after curettage.

PMID- 11953617
TI  - Customized treatment algorithm for giant cell tumor of bone: report of a series.
AB  - Between 1991 and 2000, 30 patients with 31 resections of giant cell tumors of
      bone were treated (average followup, 4.9 years; range, 1-9.6 years).
      Intralesional resection with curettes and a high-speed burr and reconstruction
      with polymethylmethacrylate cementation or bone grafting was used for
      salvageable, nonexpendable bones. Wide resection and allograft reconstruction was
      done in nonexpendable bones that were too destroyed for salvage. Adjuvant
      treatments were used for all intralesional procedures and when wide resection
      with a close margin was obtained. Adjuvant treatments included hydrogen peroxide
      instillation in 30 patients, electrocautery in 27 patients, phenol irrigation in
      26 patients, sterile water irrigation in 15 patients, and polymethylmethacrylate
      cementation in 15 patients. There have been only two (6.4%) local recurrences,
      one in bone and one in soft tissue. Both patients had intralesional resections
      initially and both had salvage procedures with wide resections of the recurrent
      tumors. The 5-year recurrence-free survivorship was 93%. A delayed ray amputation
      for failed bone graft of the little finger was the only amputation. In all other
      patients, a functional limb was preserved. Wide resection only is required when
      bone salvageability is impractical. Intralesional curettage and high-speed burr
      resection, when supplemented with the adjuvant therapies as described, is
      adequate for the majority of patients with giant cell tumor of bone. A proposed
      treatment algorithm is presented.

PMID- 11953618
TI  - Primary bone lymphoma in 24 patients treated between 1955 and 1999.
AB  - The authors present their experience in the treatment of 24 patients with primary
      bone lymphoma. Eighty-one patients treated between 1955 and 1999 were evaluated,
      and 57 were excluded because of misdiagnosis. The male to female ratio was 7:5
      and the median age was 38.5 years (range, 18-69 years). Two patients had human
      immunodeficiency virus. Seventeen patients had intermediate-grade lymphomas
      (Working Formulation), nine patients had centroblastic subtype (Kiel), and 22
      patients had B immunophenotype. Nine patients had combined treatment with
      chemotherapy and radiation therapy, and nine patients had chemotherapy alone. The
      mean followup was 13.2 years (range, 1.5-37.3 years). Three patients had surgery,
      two because of subtrochanteric fractures (one patient had closed reduction and
      internal fixation and the other patient had resection and endoprosthesis
      reconstruction). The third patient presented with myelocompression at the
      thoracic level, and he had decompression surgery. Only one patient had radiation
      therapy and two patients had no treatment. There have been no local recurrences
      in 17 patients (70.8%). Seven patients (29.2%) died with evidence of disease
      within a followup of 11 months. The results of the current study showed that
      patients with primary bone lymphoma have a good prognosis when they are treated
      with chemotherapy, regardless of whether radiation therapy was given. Surgery
      usually is appropriate for patients with fractures.

PMID- 11953619
TI  - Nerve sheath catheter analgesia after amputation.
AB  - Although continuous infusion of local anesthetic through nerve sheath catheters
      provides excellent pain control after amputation, the influence of this technique
      on the incidence of phantom limb pain is controversial. The current retrospective
      study examined the influence of continuous nerve sheath catheter analgesia and
      primary anesthetic technique (general or regional anesthesia) on the incidence of
      phantom limb pain. After institutional review board approval, data were gathered
      on patients who had amputation from 1990 to 1999. Medical records were reviewed
      to determine the level of and indication for amputation, age at time of
      amputation, current disease status, date of diagnosis and surgery, and primary
      anesthetic technique. Six months after amputation, preoperative pain, phantom
      limb sensations, and phantom limb pain were assessed using a verbal scale ranging
      from 0 (no pain) to 10 (worst pain) and methods of pain control also were
      evaluated. Thirty-nine patients completed the study. The incidence of phantom
      limb pain (visual analog scale score > or = 3) was 67% and was lower than the
      historic incidence (80%) before the use of this analgesia technique. Incidence of
      phantom limb pain was higher for patients requiring proximal versus distal
      amputations. The primary anesthetic technique (general versus regional) did not
      affect the incidence of phantom limb pain. Long-term followup showed that the
      incidence of phantom limb pain in patients receiving continuous nerve sheath
      catheter infusion is lower than previously reported for patients who had
      amputation for oncologic indications.

PMID- 11953620
TI  - The treatment of Ewing's sarcoma of bone at the University of Florida: 1969 to
      1998.
AB  - Since 1969, 144 patients with previously untreated Ewing's sarcoma of bone were
      entered in prospective protocols at the University of Florida. From 1969 through
      1981, three institutional protocols were used, and some patients were entered
      into the First Intergroup Ewing's Sarcoma Study. Starting in 1982, an attempt was
      made to intensify treatment, with patients divided according to their primary
      tumor size into standard-risk (< or = 8 cm in maximum diameter) and high-risk
      groups. Patients with metastases at diagnosis also were considered high risk. The
      standard-risk protocols (Number 1 and Number 2 specified treatment with
      chemotherapy considered to be standard for the era; the patients who were high
      risk had standard chemotherapy followed by end-intensification. Treatment for
      patients with metastases at diagnosis was intensified additionally in 1993 with a
      protocol (high-risk protocol Number 5) specifically designed just for these
      patients. The absolute survival rate of all patients treated before 1982 was 50%
      at 5 years for patients without metastases at diagnosis and 18% for patients with
      metastases. Patients with small primary lesions had a better survival rate than
      patients with large primary lesions. After 1982, the 5-year survival rate for
      patients treated on the standard-risk protocols was 53% (1985-1998), whereas for
      high-risk protocols the 5-year survival rate was 63%. Survival rates were better
      for younger patients at diagnosis and for patients who responded well to
      induction chemotherapy, indicating that future trials may need to tailor therapy
      based on the response to induction chemotherapy.

PMID- 11953621
TI  - Comparison of quality of life after amputation or limb salvage.
AB  - In the past, amputation was the standard method of treatment for patients with
      sarcomas in the extremity but limb-sparing procedures now are much more frequent.
      A computerized questionnaire automatically adjusted for gender, age, diagnosis,
      site, and treatment was sent to 2200 patients with high-grade sarcomas who had
      been treated during the past 25 years. Using the data, it was possible to study
      and compare the response from 66 patients who had an amputation and 342 patients
      with a limb-sparing procedure for a lower extremity neoplasm. More males had an
      amputation, but no differences were observed in the ages of the two groups. The
      outcomes for the two groups were similar. Patients who had limb-sparing
      procedures did not have a significant improvement in the ability to ambulate,
      climb stairs, drive a car, or be employed. More of the patients with amputations
      required walking aids and participated in sports activities at almost the same
      rate as the patients who had limb-sparing procedures. Patients who had
      amputations had no more anxiety, drug-dependence, depression, sleep problems, or
      limitation of sexual performance than patients who retained their limbs. The
      patients with amputations had more children and fewer menstrual problems;
      however, they were far less satisfied with their status at early ages than at
      later periods in their lives.

PMID- 11953622
TI  - Durability and strength of Steinmann pin augmentation in cemented tibial defects.
AB  - It has been argued that Steinmann pin augmentation does not improve the
      biomechanics of polymethylmethacrylate reconstruction for massive defects of
      bone. The current authors investigated whether pin augmentation of
      polymethylmethacrylate in the reconstruction of noncontained defects of bone
      improved the biomechanical properties of the reconstruction as compared with
      polymethylmethacrylate alone when minimal or large bone porosity is present.
      Large noncontained defects were created in 10 pairs of human tibias. In Group 1,
      five left tibias had reconstruction with polymethylmethacrylate augmented with
      three, 5-mm diameter by 10-mm deep holes into lateral condyle cancellous bone.
      Right tibias had identical reconstruction with three, 3/16-inch threaded pins
      placed into the medullary canal. In Group 2, three, 10-mm diameter by 10-mm deep
      holes were created in both pairs. The left tibia had polymethylmethacrylate
      reconstruction and the right tibia had polymethylmethacrylate and pin
      augmentation. Specimens were subjected to 2000 compressive cycles then loaded to
      failure. In Group 1, cycles and load to failure were significantly lower in
      reconstructions without pins compared with reconstructions with pins. No
      significant difference was observed between reconstruction techniques in Group 2.
      In reconstructions without pins, large diameter holes had significantly better
      cyclical durability. Pins improved survival compared with no pins.

PMID- 11953623
TI  - Animal model for evaluation of soft tissue ingrowth into various types of porous
      coating.
AB  - Results from several studies have suggested that soft tissue ingrowth into porous
      coating can serve as a biologic containment mechanism to prevent particulate
      debris migration by sealing off the effective joint space. Therefore, a rabbit
      animal model was developed to investigate soft tissue ingrowth into various types
      of metallic rods. After implantation of several types of coated and smooth rods
      within the thigh musculature of rabbits, a thick encapsulation of soft tissue was
      observed around porous-coated rods whereas a nonadherent pseudosynovial-lined
      cavity was observed around smooth rods. Within 3 weeks, soft tissue had grown
      into the three different types of porous coating on the rods. Histologic
      evaluation verified that maturation of this ingrowth tissue occurred by 12 weeks.
      Incomplete soft tissue ingrowth occurred into the depths of large-bead (590-840
      mm) porous-coated surfaces. Soft tissue separation from the bead surfaces was
      observed at 12 weeks in the porous-coated implants that also had been coated with
      a thin layer of tricalcium phosphate. These findings suggest that soft tissue
      ingrowth can be expected to occur into the porous coatings tested, but that
      tricalcium phosphate should not be used as an additional surface coating to
      obtain long-term adherence of circumferential soft tissue ingrowth.

PMID- 11953624
TI  - Exact focusing of extracorporeal shock wave therapy for calcifying tendinopathy.
AB  - A controlled prospective randomized study was designed to analyze the effect of
      extracorporeal shock wave therapy on calcifying tendinopathy of the shoulder
      focused on the calcified area or the origin of the supraspinatus tendon. Fifty
      patients were included in the study and were treated with a Storz Minilith Sl-1
      shock wave generator. The first group of patients received 4000 impulses
      (positive energy flux density, 0.78 mJ/mm2) in two treatment sessions after
      receiving local anesthesia at the origin of the supraspinatus tendon. Patients in
      the second group received extracorporeal shock wave therapy at the calcified
      area. Follow-ups were done 12 weeks and 1 year after treatment by an independent
      observer. An increase of function and a reduction of pain occurred in both
      groups. Statistical analyses showed a significant superiority of extracorporeal
      shock wave application at the calcified area in the primary end point (Constant
      and Murley score). Therefore, exact fluoroscopic focusing of extracorporeal shock
      wave therapy at the calcific deposit for treatment of calcifying tendinopathy of
      the supraspinatus muscle is recommended. Based on these results, extracorporeal
      shock wave application should be focused fluoroscopically with appropriate shock
      wave generators.

PMID- 11953625
TI  - Results of surgery after failed attempt at repair of irreparable rotator cuff
      tear.
AB  - Twelve patients who had surgery to repair a rotator cuff tear, which could not be
      repaired because the residual tendon tissue was of poor quality, insufficient, or
      both, were followed up for a mean of 33 months. At surgery, the deltoid was
      detached from the acromion for 4 to 6 cm and an acromioplasty was done.
      Preoperatively, all patients except one had mild to severe pain. The mean active
      forward flexion, abduction, and external rotation were 75 degrees, 61 degrees,
      and 22 degrees, respectively. After surgery, of the 11 patients who had shoulder
      pain preoperatively, 10 reported partial relief of pain and one was pain-free.
      However, shoulder function deteriorated in 11 patients and remained unchanged in
      one patient who had a pseudoparalytic shoulder before and after surgery. The mean
      postoperative values of forward flexion, abduction, and external rotation were 49
      degrees, 43 degrees, and 16 degrees, respectively. Only one patient was satisfied
      with the result of surgery because of pain relief. Two patients had repeat
      surgery (total shoulder replacement or latissimus dorsi transfer) 6 and 4 months
      after the index surgery because of unsatisfactory functional results. Attempts at
      open repair of an irreparable cuff tear should be avoided because functional
      results generally are poor. When there is a risk that an irreparable tear will be
      found, open surgery should not be done or alternative procedures should be
      planned before surgery.

PMID- 11953626
TI  - Hypofibrinolysis, lipoprotein(a), and plasminogen activator inhibitor.
AB  - Parameters of hypofibrinolysis and thrombophilia were assessed in 20 consecutive
      patients with bone marrow edema sydrome of the hip who lacked typical risk
      factors for osteonecrosis. Twenty healthy subjects, matched for age and gender,
      served as the control subjects. In patients with bone marrow edema syndrome,
      elevated levels of lipoprotein(a) and plasminogen activator inhibitor were found
      in nine (45%) and two patients (10%), respectively. Elevation of lipoprotein(a)
      was present in two patients in the control group; however, plasminogen activator
      inhibitor levels were normal in this group. Mean levels of lipoprotein(a) were
      34.8 mg/dL in the patients with bone marrow edema versus 13.8 mg/dL in the
      control subjects. Mean concentrations of plasminogen activator inhibitor,
      apolipoproteins, lipid metabolism parameters, and indicators of thrombophilia did
      not differ in both groups. Pulsed field gel electrophoresis and Southern blots
      confirmed the presence of pathologic allelotypes in three patients with elevated
      levels of lipoprotein(a) who had a familial occurrence of bone marrow edema
      syndrome. These findings also underline a fundamental role of hypofibrinolysis,
      mediated by elevated levels of lipoprotein(a) or plasminogen activator inhibitor,
      or both, in the former idiopathically considered etiology of the bone marrow
      edema syndrome of the hip.

PMID- 11953627
TI  - Complications of joint arthroplasty in patients with end-stage renal disease on
      hemodialysis.
AB  - The mortality and morbidity after hip and knee arthroplasty were reviewed
      retrospectively during a 3-year period in 14 patients who had chronic renal
      failure and who were receiving hemodialysis. The patients had a primary total hip
      or knee replacement, or a revision arthroplasty or resection arthroplasty. Four
      of the patients (29%) died in the hospital during the postoperative period. One
      of the seven patients (14%) having a primary joint replacement died, whereas
      three of the seven patients (86%) having a revision or resection died. Every
      patient had multiple medical comorbidities, and every patient had a complication.
      The results indicate that arthroplasty procedures, especially revisions and
      resections, in this patient population are associated with a high rate of
      complications and death, and that in-depth informed consent should be provided
      for all patients contemplating these procedures. Meticulous treatment of medical
      comorbidities is mandatory. Finally, data in the literature and in the current
      report question whether joint arthroplasty procedures should be done in patients
      with end-stage renal disease who are receiving hemodialysis.

PMID- 11953628
TI  - Patellar component resection arthroplasty for the severely compromised patella.
AB  - When severe bone loss precludes reimplantation of a new patellar component during
      revision knee arthroplasty, the treatment options include patellar bone grafting,
      patellar component resection arthroplasty, and patellectomy. The purpose of this
      study was to evaluate the clinical and functional results of patellar component
      resection arthroplasty for the severely compromised patella for which insertion
      of another patellar component was not possible. Thirty-five knees (31 patients)
      were treated with patellar component resection arthroplasty for aseptic patellar
      component failure associated with severely compromised patellar bone stock.
      Followup averaged 7.9 years (range, 2-18 years). There was a significant
      improvement in Knee Society pain and function scores. Pain relief was more
      dramatic than functional improvement. The range of motion also improved
      significantly and in particular preoperative extensor lag was resolved in the
      majority of patients. Patients treated with isolated patellar resection
      arthroplasty were more likely to have continuing pain and require reoperation
      compared with patients who had concomitant revision of the tibial and femoral
      components. Correct positioning and the stability of tibial and femoral
      components should be tested carefully at the time of patellar resection
      arthroplasty and considered for revision if malpositioned either axially or
      rotationally.

PMID- 11953629
TI  - Lateral patellar retinaculum tension in patellar instability.
AB  - The patellar retinaculum is important in patellar tracking. However, little
      attention has been paid to the biomechanics of the retinaculum. This study
      assessed the change in tension of the lateral patellofemoral ligament before and
      after anteromedial tibial tubercle transfer for patellar instability. Twenty
      seven knees in 21 patients were studied and the mean age of the patients at
      surgery was 19 years. A buckle transducer was clamped on the lateral
      patellofemoral ligament and the transducer was calibrated to zero with the knee
      at full extension. The knee then was flexed 30 degrees, 60 degrees, 90 degrees,
      and 120 degrees, and the transducer recorded changes in tension within the
      lateral patellofemoral ligament. After anteromedial tibial tubercle transfer,
      lateral patellofemoral ligament tension was measured in the same manner. Although
      average lateral patellofemoral ligament tension increased with knee flexion with
      the maximum at 120 degrees flexion, these changes showed four different patterns
      measuring variability of patellar instability. An increase of lateral
      patellofemoral ligament tension after anteromedial tibial tubercle transfer meant
      that lateral retinacular release should be done concurrently to balance patellar
      tracking. This information may be useful in deciding the appropriate surgical
      procedure for each patient.

PMID- 11953630
TI  - Rehabilitation after hamstring anterior cruciate ligament reconstruction.
AB  - A prospective comparative study was conducted involving 62 patients to determine
      the effects and limits of accelerated rehabilitation on clinical outcome. The
      study focused on whether aggressive rehabilitation after anterior cruciate
      ligament reconstruction with the doubled semitendinosus and gracilis tendon
      autograft results in stretching the graft. Thirty patients had postoperative
      rehabilitation according to the current conservative protocol, and 32 patients
      had rehabilitation using an accelerated regime. Each patient was evaluated
      subjectively and objectively 36 months or more after surgery. Concerning the side
      to-side difference in the anterior laxity, 87% of the patients in the
      conservative rehabilitation group had 3 mm or less and 80% of the patients in the
      accelerated rehabilitation group had the same acceptable laxity. There was no
      significant difference between the two groups. Muscle torque was restored
      significantly earlier in the patients in the accelerated rehabilitation group
      than in the patients in the conservative rehabilitation group. Nine months after
      surgery, however, there were no significant differences in the torque between the
      two groups. Accelerated rehabilitation significantly increased the incidence of
      knee effusion during rehabilitation. This study showed that acceleration of
      postoperative rehabilitation could rapidly restore muscle strength without
      significantly compromising graft stability in anterior cruciate ligament
      reconstruction with the doubled hamstring tendon autograft. However, this study
      also showed that acceleration significantly increases the incidence of synovitis.
      Acceleration of postoperative rehabilitation has advantages and disadvantages for
      clinical outcome after anterior cruciate ligament reconstruction.

PMID- 11953631
TI  - Bilateral congenital subtalar dislocation: a case report.
AB  - Fixed bilateral congenital subtalar dislocations were identified in a 2.5-year
      old boy. The patient had been treated previously with a short-leg cast on each
      foot for 2 months. On presentation the patient ambulated on the medial malleoli
      and medial aspects of his feet. The patient's activity was limited by pain. At
      2.5 years of age, open reduction and pinning of bilateral subtalar joints with
      soft tissue release and lengthening of the achilles, peroneal, and extensor
      tendons was done. A thick fibrous band connected the talus and calcaneus
      laterally. Postoperative treatment included casting for 12 weeks and wearing
      rigid ankle-foot orthoses which he used for 8 years. There was no recurrence at
      10-year followup. The patient has been brace-free for 2 years and is able to
      ambulate and play school sports without pain. The patient's subtalar range of
      motion is normal. Radiographic alignment is near normal without degenerative
      changes. To the authors' knowledge, there has been no previous report of this
      condition in the literature.

PMID- 11953632
TI  - Limb salvage using original low heat-treated tumor-bearing bone.
AB  - Limb salvage, using original low heat-treated tumor-bearing bone and a
      conventional joint prosthesis, was done in six patients with malignant tumors of
      the proximal humerus (one patient with chondrosarcoma and five patients with
      osteosarcoma) and in six patients with tumor of the proximal femur (two patients
      with malignant spindle cell sarcoma and four patients with osteosarcoma). Wide
      excision of the lesion was done and the tumor and surrounding soft tissues were
      removed. The excised bone was treated with heat and the prosthesis was inserted
      into the treated bone and fixed with cement. This construct was reinserted into
      the original site and anchored to the host bone with a plate. The overall union
      rate of the low heat-treated bone with normal host bone was 91.7%, and the mean
      union time was 4.6 months (range, 3-7 months) after surgery. The functional
      result of the proximal femur and proximal humerus were 76.7% and 56.8%,
      respectively, using the Musculoskeletal Tumor Society functional evaluation
      system. Complications included hip dislocation in one patient, fracture of the
      low heat-treated bone in two patients, and absorption of the low heat-treated
      bone of the humerus in four of six patients. The 5-year survival rate of the low
      heat-treated tumor-bearing bone was 83.3% using Kaplan-Meier survival analysis.
      Based on the results of this study, limb salvage using original low heat-treated
      tumor-bearing bone seems to be effective in treating primary bone sarcoma with
      high survival and acceptable complication rates, circumventing the complications
      of allograft bone.

PMID- 11953633
TI  - Osteoid osteoma and osteoblastoma of the spine: experiences with 22 patients.
AB  - Osteoblastomas and osteoid osteomas of the spine are relatively rare bone-forming
      tumors. Between 1980 and 1999, nine patients with osteoid osteoma and 13 patients
      with osteoblastoma had surgery for their tumors. Four tumors were in the cervical
      spine, six tumors were in thoracic spine, 10 tumors were in the lumbar spine, and
      two tumors were in the sacrum. The average duration between onset of pain and
      surgery was 16.6 months in 12 patients treated in the 1980s and 8.6 months in 10
      patients treated in the 1990s. Seventeen patients had scoliosis. In nine of 10
      patients with magnetic resonance imaging scans, high signal intensity areas in
      the muscles and bone around the lesion were seen. Two of nine patients with
      osteoid osteoma and nine of 13 patients with osteoblastoma had neurologic
      disorders before treatment. All patients had open resection of the lesions. Two
      patients with osteoid osteoma had relapse because of incomplete resection,
      necessitating a second excision. In 16 of 17 patients with preoperative spinal
      deformity, the deformity improved during followup. With development of modern
      imaging techniques, exact surgical planning may become possible; however, in some
      cases, intraoperative complete resection of the lesion still is difficult.

PMID- 11953634
TI  - Palmar plating for dorsally displaced fractures of the distal radius.
AB  - Extensor tendon rupture and irritation caused by implants or surgical
      intervention are serious complications in the treatment of fracture of the distal
      radius when a dorsal approach is used. To prevent complications, the dorsally
      displaced fracture of the distal radius was treated using a palmar approach. The
      subjects were 18 men and 15 women with a mean age of 54 years at the time of the
      injury (range, 23-75 years). All the patients had internal fixation with a plate
      and screws using the palmar approach. Union was achieved in all patients.
      Radiographic parameters, including the palmar tilt, radial inclination, radial
      length, and ulnar variance have been maintained since the operation. According to
      the rating scale of Gartland and Werley, there were 12 excellent, 20 good, and
      one fair result. There were no extensor tendon injuries that occurred during use
      of the palmar approach in this small series of patients. Palmar plating can be
      safe and effective for treatment of a dorsally displaced fracture of the distal
      radius.

PMID- 11953635
TI  - Digital radiographs in the assessment of distal radius fracture parameters.
AB  - The purpose of the current study was to assess the reliability of measurement of
      distal radius fracture parameters using digital radiographs. Digital radiographs
      and corresponding plain radiographs of the wrists of 20 patients with
      intraarticular distal radius fractures were used to measure radial inclination,
      palmar tilt, radial height, and articular step-off. The plain radiographs and
      digital images were evaluated independently by three examiners in two sessions.
      The plain radiographs were assessed using a standard goniometer (manual
      measurements) whereas the digitized radiographs were evaluated using imaging
      software to do the computer-assisted measurements. The interobserver and
      intraobserver reliability were measured using repeated measures analysis of
      variance and weighted kappa statistics. Measurement of the digital images
      improved the interobserver reliability of measurement of palmar tilt from
      substantial to excellent, radial height from moderate to substantial, and
      articular step-off from fair to moderate. Similarly, intraobserver reliability
      increased from moderate to substantial when measuring radial height. In no
      instance (between or within observers) did the level of reliability decrease when
      using digital images for fracture evaluation. The current data suggest that the
      reliability of measurements of angular and linear fracture parameters of distal
      radius fractures is similar between plain and digital radiographs.

PMID- 11953636
TI  - Biologic behavior of an in vitro hydrated collagen gel-human tenocyte tendon
      model.
AB  - An in vitro human tenocyte-collagen gel model was developed to study tenocyte
      mediated Type I collagen fibril reorganization, proliferation, and Type I
      collagen gene expression. Human tenocytes, obtained from extrasynovial forearm
      flexor tendons from children 5 to 10 years of age were cultured on plastic or in
      a cylinder of hydrated Type I collagen gel. Collagen solution was seeded with
      human tenocytes at 5 x 10(5) cells/mL and gelled in cylinder molds; gel cylinders
      without human tenocytes served as controls. Gel cylinders were pinned to troughs
      to create noncompliance. The gel cylinders were analyzed for collagen
      birefringence and cell shape at 7 and 21 days and for proliferation and gene
      expression for Type I collagen at 7 days. Under conditions of noncompliance,
      human tenocytes reoriented Type I collagen into longitudinal bundles resembling
      the parallel organization of collagen in native tendons. Tenocyte shape became
      fusiform between the collagen bundles which mimics the morphologic features of a
      tenocyte in vivo. The structural changes in the tenocytes and matrix are
      accompanied by downregulation of human tenocyte proliferation and Type I collagen
      gene expression. When released from the gel cylinder and grown again on plastic,
      human tenocytes resume proliferation and Type I collagen gene expression. The
      human tenocytes in this in vitro gel cylinder model system control fibril
      reorganization and proliferation, resembling their behavior during the
      development and repair of native tendons.

PMID- 11953637
TI  - How correctly does an intramedullary rod represent the longitudinal tibial axes?
AB  - In a robot-assisted procedure for preparing the tibia in total knee arthroplasty,
      developed in the authors' laboratory, an intramedullary rod is used to register
      the tibia. In 18 formalin-fixed tibias, the difference in orientation was
      calculated between the intramedullary rod and several longitudinal tibial axes
      used in clinical practice. This was done using roentgenstereophotogrammetric
      analysis. Three tibial axes and two insertion techniques were considered. In
      three-dimensional space, small differences between the axes are observed. The
      results showed a high standard deviation, indicating the importance of anatomic
      differences. In the frontal plane, the difference in orientation between rod and
      tibial axes never exceeded +/- 2 degrees. In the sagittal plane, the observed
      differences were larger. Significant differences between the considered axes
      appeared. The results of the two insertion techniques were not significantly
      different. Because an intramedullary rod frequently is used for alignment of the
      tibia in conventional surgery, these results also are valuable for conventional
      surgery. In the current study, the accuracy of the intramedullary alignment is
      examined, without influences of the sawing procedure. Moreover, the study is not
      limited to the frontal plane; the total accuracy in three-dimensional space, and
      the accuracy in the frontal and the sagittal planes were studied.

PMID- 11953638
TI  - A 10-year-old boy with hip pain.

PMID- 11953641
TI  - Energy attenuator for pediatric application of an automated external
      defibrillator.
AB  - Although automatic external defibrillators (AEDs) are extensively deployed to
      rapidly treat sudden cardiac arrest in adults, their applicability for children
      is presently limited. It is desirable to extend the indications for this
      lifesaving equipment to all ages, even though AED application to children will be
      rare compared with adults. It is imperative that the inherent simplicity of
      present adult AED operation not be compromised to extend its use to include
      children. We propose a method that does not affect the normal operation of an AED
      on adults. For adults, unmodified AEDs would be used normally with adult
      electrodes. However, special pediatric electrodes would be available as a
      disposable accessory. When used with the AED, the delivered energy would be
      reduced within the electrodes, and only a portion of the energy output by the AED
      would be delivered to the pediatric patient. These electrodes could be used in
      conjunction with currently deployed AEDs with electrocardiographic analysis
      algorithms appropriate for children. This eliminates the need for a separate AED
      specifically for children or the purchase of a new AED with pediatric capability
      to replace previously deployed models.

PMID- 11953642
TI  - Determination of the noise source in the electrocardiogram during cardiopulmonary
      resuscitation.
AB  - During cardiopulmonary resuscitation (CPR), the electrocardiogram (ECG) is often
      obscured by noise. This noise is in the form of baseline variations in the ECG,
      which often necessitate stopping chest compressions to adequately assess the ECG.
      Because survival from cardiac arrest has been shown to be related to blood flow
      generated during CPR, and because interruption of chest compressions will reduce
      blood flow, survival may be compromised by these interruptions. Three possible
      sources for the noise were considered: the heart, which is deformed during CPR,
      which may introduce a mechanical-electrical interaction and alter the normal
      electrical pattern of the heart; the thoracic cavity, which may have large
      impedance variations because of CPR and thereby modulate the ECG; and the skin
      electrode interface, which may be mechanically disturbed during CPR and thus
      produce polarization potentials that cause additional noise. CPR studies were
      performed on five dogs by using four different test conditions and six different
      types of electrodes. The test conditions were: electrode motion, which allowed
      mechanical disturbances of the skin-electrode interface without altering the
      thoracic impedance or deforming the heart; vest CPR; manual CPR; and respiration.
      The myocardial ECG, the bipolar and unipolar surface ECGs, and the thoracic
      impedance were monitored. Different types of surface ECG electrodes were used to
      determine whether the noise was dependent on electrode type or size. There were
      no baseline variations in the myocardial ECG during any of the test conditions.
      The thoracic impedance did vary during CPR, but the variations were temporally
      uncorrelated to the baseline variations in the ECG, and the variations were of
      similar magnitude as the variations caused by respiration, which produced no
      baseline changes in the ECG. Finally, the magnitude of the baseline variations in
      the ECG was substantially different for electrodes of different sizes and shapes,
      and electrode motion produced baseline variations that were identical to those
      produced during CPR. Therefore, it was concluded that the source of the noise in
      the ECG during CPR is the skin-electrode interface and, specifically, that the
      noise is related to the electrical properties of the electrode.

PMID- 11953643
TI  - Pharmacologic defibrillation.
AB  - Ventricular fibrillation (VF) is generally sustained. The mechanism is, at least
      in part, caused by progressive accumulation of intracellular sodium and calcium
      ions during untreated ventricular fibrillation, which subsequently increases
      defibrillation threshold. Cariporide, a potent and specific inhibitor of the
      sodium-hydrogen exchanger, has been shown to reduce intracellular sodium and
      calcium concentration in the setting of myocardial ischemia and reperfusion. We
      hypothesized that cariporide would facilitate defibrillation from prolonged
      ventricular fibrillation in a rodent model of cardiac arrest and resuscitation.
      Fifteen Sprague-Dawley rats were randomized to receive bolus injections of
      cariporide or placebo in a dose of 3 mg/kg into the right atrium either 5 mins
      before or at 8 mins after onset of ventricular fibrillation. Ventricular
      fibrillation was electrically induced and untreated for 8 mins. Precordial
      compression together with mechanical ventilation was then started and continued
      for an interval of 8 mins before attempted electrical defibrillation. All but one
      placebo-treated animal were successfully resuscitated. Spontaneous defibrillation
      with restoration of circulation was observed in both cariporide pretreatment and
      treatment groups but in none of the placebo-treated animals. The duration of
      postresuscitation survival was significantly increased in animals pretreated with
      cariporide. Therefore, sodium-hydrogen exchanger inhibitors may provide new
      options in settings of cardiopulmonary resuscitation to facilitate
      defibrillation.

PMID- 11953644
TI  - Arginine vasopressin during cardiopulmonary resuscitation: laboratory evidence,
      clinical experience and recommendations, and a view to the future.
AB  - When stimulating adult pigs with ventricular fibrillation or postcountershock
      pulseless electrical activity for cardiopulmonary resuscitation, vasopressin
      improved vital organ blood flow, cerebral oxygen delivery, ability to be
      resuscitated, and neurologic recovery better than epinephrine. In pediatric
      preparations with asphyxia, epinephrine was superior to vasopressin, whereas in
      both pediatric pigs with ventricular fibrillation and adult porcine models with
      asphyxia, combinations of vasopressin and epinephrine proved to be highly
      effective. This may suggest that a different efficiency of vasopressors in
      pediatric vs. adult preparations and different effects of dysrhythmic vs.
      asphyxial cardiac arrest on vasopressor efficiency may be of significant
      importance. Whether these theories can be extrapolated to humans is unknown at
      this time. In patients who experienced out-of-hospital ventricular fibrillation,
      a larger proportion of patients treated with vasopressin survived 24 hrs compared
      with patients treated with epinephrine; during in-hospital cardiopulmonary
      resuscitation, comparable short-term survival was found in groups treated with
      either vasopressin or epinephrine. Currently, a large trial comprising patients
      who experience out-of-hospital cardiac arrest and who are treated with
      vasopressin vs. epinephrine is ongoing in Germany, Austria, and Switzerland. The
      new cardiopulmonary resuscitation guidelines of both the American Heart
      Association and the European Resuscitation Council consider 40 units of
      vasopressin intravenously and 1 mg of epinephrine intravenously equally effective
      for the treatment of adult patients with ventricular fibrillation; however,
      because of a lack of clinical data, no recommendation for vasopressin has been
      made for adult patients with asystole and pulseless electrical activity or for
      pediatric patients.

PMID- 11953646
TI  - Expanding automatic external defibrillators to include automated detection of
      cardiac, respiratory, and cardiorespiratory arrest.
AB  - The new Guidelines of the American Heart Association state that lay rescuers can
      no longer rely on the manual pulse check to confirm cardiac arrest in an
      unresponsive patient. We were therefore prompted to develop a method for
      automated determination of the presence or absence of cardiac contraction and
      breathing. The technique was designed to be incorporated into conventional
      automated external defibrillators and to work in conjunction with the information
      derived from rhythm analyses by the automated defibrillator. Using conventional
      electrocardiographic sensing and defibrillation electrodes, the transthoracic
      impedance was measured by passing a constant amplitude alternating current of 5
      mA through the thorax at a frequency of 35 kHz. In five anesthetized male
      domestic swine, we observed pulses that were coincident with cardiac contraction
      documented by esophageal echocardiography. In addition, we observed larger
      signals of lower frequency that were time related to ventilation and documented
      by capnography. Both signals disappeared after inducing ventricular fibrillation.
      The impedance measurement identified respiratory arrest in anesthetized animals
      and primary cardiac arrest after ventricular fibrillation was induced. The
      cardiac arrest detector is therefore likely to augment the current information
      provided by automated defibrillators and to allow for more precise verbal
      prompting of lay rescuers.

PMID- 11953647
TI  - Hypercatabolism and hypermetabolism in wasting states.
AB  - The year 2001/2002 has been marked by a number of exciting new results for our
      understanding of anabolic and catabolic mediators and their participation in
      wasting states, as reflected by the contents of this section. It becomes ever
      more apparent that a clear understanding of how to shut off hypercatabolic and
      hypermetabolic processes is needed to underpin effective strategies for wasting
      syndromes. A particularly interesting development in the control of degradative
      processes in skeletal muscle is the discovery of several muscle-specific
      ubiquitin ligases. These enzymes, which confer specificity to the degradation of
      myofibrillar proteins and are situated in a pathway of proteolysis common to a
      variety of wasting states, may prove to be a valuable point of intervention in
      muscle atrophy. In the clinical arena, studies on non-small cell lung cancer
      patients as well as broader patient populations with solid tumours provide more
      evidence for a high incidence of hypermetabolism as well as low energy intake.
      The best therapies currently available for the cancer cachexia/anorexia syndrome
      have numerous limitations and tend mainly to attenuate losses rather than to
      promote a net gain of weight or lean body mass. Sustained hypermetabolism over
      the long course of disease progression constitutes an important contributor to
      negative energy balance, and its presence is likely to be a limiting factor to
      the success of current treatment approaches.

PMID- 11953648
TI  - Eicosanoid-dependent cancer cachexia and wasting.
AB  - The reversal of catabolic processes remains a significant challenge related, in
      part, to their complexity and our incomplete understanding of the mechanisms
      involved. The eicosanoids are key players in the inflammatory process and have
      been implicated in the process of cancer cachexia. They are unsaturated C20 fatty
      acids which can be separated into two main groups: the lipoxygenase products
      including leukotrienes and lipoxins, and the prostanoids including
      prostaglandins, prostacyclin and thromboxane. This review examines the biology of
      the eicosanoids and the evidence of a role for the eicosanoids in cancer cachexia
      and wasting.

PMID- 11953649
TI  - Apoptotic signaling in skeletal muscle fibers during atrophy.
AB  - This brief review discusses an exciting area in skeletal muscle research, namely
      the role of apoptosis in relation to muscle activity. Apoptotic cell death
      appears to occur during atrophy as a mechanism for removing part of the myofiber
      without affecting its viability. Recent developments in our understanding of the
      signaling of muscle catabolism and new insights into the therapeutic outlets are
      highlighted. The roles of mitochondria, Ca2+, and tumor necrosis factor alpha in
      activating the caspase cascade are discussed. We speculate that atrophy-induced
      apoptosis is a normal regulatory process that the cell can use to reduce the
      number of organelles, thus ensuring optimal cell function.

PMID- 11953650
TI  - Nuclear factor kappa B signaling in catabolic disorders.
AB  - The nuclear factor kappa B family of inducible transcription factors regulates
      the expression of many genes. Nuclear factor kappa B has been implicated in
      autoimmune and inflammatory diseases, infection, cell survival, and cell
      transformation with subsequent promotion of cancer. In this review, we summarize
      features of nuclear factor kappa B regulation in several catabolic disorders, and
      describe its role in normal cellular function as well as provide an important
      link to the role of scaffold proteins, cellular receptors, and other cell
      signaling pathway kinases that converge on the nuclear factor kappa B signaling
      cascade. Subsequently, we focus on the role of nuclear factor kappa B in cell
      survival and oxidative stress. Finally, potential therapeutic strategies are
      discussed that may modify nuclear factor kappa B activity including endogenous
      antioxidant systems and the Fas/FasL system. However, challenges still remain in
      developing new therapeutic strategies that not only include identifying novel
      agents, but also by improving clinical endpoint definitions and by defining
      biological efficacy.

PMID- 11953651
TI  - Skeletal muscle uncoupling protein 3 (UCP3): mitochondrial uncoupling protein in
      search of a function.
AB  - The uncoupling protein 1 homologue, uncoupling protein 3, is able to uncouple
      adenosine triphosphate production from mitochondrial respiration, thereby
      dissipating energy as heat and affecting the efficiency of energy metabolism.
      Uncoupling protein 3 is expressed predominantly in skeletal muscle, and has been
      associated with whole-body energy metabolism. However, on the basis of present
      evidence it has been concluded that the primary function of uncoupling protein 3
      is not in the regulation of energy expenditure. For example, fasting, an energy
      expenditure attenuating condition, upregulates uncoupling protein 3 expression,
      and uncoupling protein 3 knockout mice have a normal metabolic rate. The exact
      function of uncoupling protein 3 remains to be elucidated, but at present
      putative roles for uncoupling protein 3 include involvement in the regulation of
      the production of reactive oxygen species, mitochondrial fatty acid transport and
      the regulation of glucose metabolism in skeletal muscle. Because all these
      putative functions assume that uncoupling protein 3 affects mitochondrial
      coupling, a secondary effect of the function of uncoupling protein 3 might still
      be that it influences (but not regulates) energy metabolism, consistent with
      observations in linkage and association studies. Therefore, uncoupling protein 3
      remains an interesting target for pharmacological upregulation in the treatment
      of obesity and diabetes.

PMID- 11953652
TI  - Role of growth hormone, insulin-like growth factor-I, and insulin-like growth
      factor binding proteins in the catabolic response to injury and infection.
AB  - The erosion of lean body mass resulting from protracted critical illness remains
      a significant risk factor for increased morbidity and mortality in this patient
      population. Previous studies have documented the well known impairment in
      nitrogen balance results from both an increase in muscle protein degradation as
      well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis.
      This protein imbalance may be caused by an increased presence or activity of
      various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1
      beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased
      concentration or responsiveness to various anabolic hormones, such as growth
      hormone or insulin-like growth factor-I. This review focuses on recent
      developments pertaining to the importance of alterations in the growth hormone
      insulin-like growth factor-I axis as a mechanism for the observed defects in
      muscle protein balance.

PMID- 11953653
TI  - Adrenergic control of protein metabolism in skeletal muscle.
AB  - This review summarizes evidence indicating that the sympathetic nervous system,
      through hormonal and neurotransmitter actions, produces anabolic, protein-sparing
      effects on skeletal muscle protein metabolism. Studies are reviewed which
      indicate that catecholamines secreted by the adrenal medulla have an inhibitory
      effect on muscle Ca(2+)-dependent protein degradation independently of other
      hormones. In addition, norepinephrine released from adrenergic terminals may
      increase the rate of protein synthesis in oxidative muscles, leading to increased
      protein accretion. Evidence is also presented that these effects seem to be
      mediated by beta(2)-adrenoceptors and cyclic adenosine monophosphate-dependent
      pathways. The understanding of the precise mechanisms by which endogenous
      catecholamines promote muscle anabolic effects may bring new perspectives for
      efficient treatment of muscle-wasting conditions and enhancement of growth
      efficacy in farm species.

PMID- 11953654
TI  - Practical nutrition support for chronic diseases in the young and the old.

PMID- 11953655
TI  - Practical aspects of intradialytic nutritional support.
AB  - A critical review of recent international literature related to the use of
      intradialytic parenteral nutrition is given. The role of intradialytic parenteral
      nutrition as a therapy in malnourished hemodialysis patients is established and
      the need for systematic monitoring of this population at high risk of
      malnutrition is emphasized.

PMID- 11953656
TI  - Nutritional aspects of liver transplantation.
AB  - Most adult and pediatric liver transplantation candidates present several
      metabolic disturbances that lead to malnutrition. Because malnutrition may
      adversely affect morbidity and mortality of orthotopic liver transplantation, it
      is very important to carefully assess the nutritional status of the waiting list
      patients. Pretransplant nutritional therapy -- enteral or parenteral -- may
      positively influence liver metabolism, muscle function, and immune status.
      Nutrition therapy should continue in the short- and also in the long-term post
      transplant periods. For malnourished patients, early post-transplant enteral or
      parenteral nutrition have been useful in improving nutritional status. Finally,
      the metabolic and nutritional care of the liver transplant donor must be
      considered to reduce allograft dysfunction indices.

PMID- 11953657
TI  - Outcome and quality of life in paediatric home parenteral nutrition.
AB  - In this review the current status of home parenteral nutrition is analysed, with
      respect to the predictability of weaning from nutritional support and the risk of
      developing major complications associated with the technique, the loss of
      vascular access and liver disease. These two complications were evaluated because
      they represent the more important indication for intestinal transplantation, the
      availability of which has changed the perspectives of patients and of physicians.
      Analysis of outcomes from the largest series allows the identification of
      patients who could be weaned from parenteral nutrition. Important prognostic
      factors in patients affected by short bowel syndrome are the length and type of
      the remnant and the time to tolerate enteral feeding. The main complications of
      therapy are sepsis, thrombosis, nutrient imbalances and liver disease. Sepsis and
      thrombosis could lead to line replacement and the loss of vascular access. Sepsis
      no longer represents a major cause of death, but it is a frequent complication.
      In some patients, it is difficult to assess the risk factors for sepsis, which is
      possibly related to a poorer outcome. The care of gut failure appears to be the
      best preventative measure for the occurrence of cholestatic liver disease, but
      further studies are needed to define the eventual role of lipid emulsion and of
      specific nutrient deficiency. The quality of life still remains to be studied:
      because home parenteral nutrition in children has a longer duration, its analysis
      is mandatory.

PMID- 11953658
TI  - Facilitated feeding in disabled elderly.
AB  - Nutrition and health are major concerns to older individuals. Whereas illness
      associated with overnutrition has been well characterized, poor health associated
      with undernutrition has received less attention. Malnutrition continues to plague
      the elderly in developed and underdeveloped countries alike, and is becoming of
      more concern as global demographic changes predict increasing proportions of
      elderly in all societies. Nutrition influences many chronic disease processes
      affecting older individuals. In addition, changes in physiology, metabolism, and
      function accompanying aging result in altered nutritional requirements. The
      enhancement and maintenance of health and function are now more possible with the
      new knowledge of nutritional needs in old age. Designing nutritional therapy to
      treat malnutrition associated with illness in older patients requires an
      understanding of the aging processes, a careful setting of treatment goals, and
      multidisciplinary collaboration.

PMID- 11953659
TI  - Practicalities of glutathione supplementation in nutritional support.
AB  - New nutraceutical products for nutritional support and antioxidant therapy such
      as glutathione require practical advice and information on the indications,
      methods and routes of administration, dosing (therapeutic drug monitoring),
      stability and physicochemical compatibility. This review is based on recent
      clinical and experimental publications in which glutathione has been used as a
      drug.

PMID- 11953660
TI  - Drug-nutrient interaction in clinical nutrition.
AB  - Drug-nutrient interactions have been recognized for decades. It is known that
      improper management of some of these interactions may lead to therapeutic failure
      or cause serious adverse effects to the patients. While most of the known drug
      nutrient interactions involve changes in oral bioavailabilities and absorption of
      the offending compounds, recent investigations suggest that different mechanisms
      also exist. A mechanism-derived classification system for drug-nutrient
      interactions has only recently been developed. This system should facilitate the
      future research and development of practice guidelines in the identification and
      management of important interactions.

PMID- 11953663
TI  - Comparison between granulocyte colony-stimulating factor and granulocyte
      macrophage colony-stimulating factor in the mobilization of peripheral blood stem
      cells.
AB  - Peripheral blood stem cells (PBSC) have become the preferred source of stem cells
      for autologous transplantation because of the technical advantage and the shorter
      time to engraftment. Mobilization of CD34+ into the peripheral blood can be
      achieved by the administration of granulocyte colony-stimulating factor (G-CSF),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), or both, either alone
      or in combination with chemotherapy. G-CSF and GM-CSF differ somewhat in the
      number and composition of PBSCs and effector cells mobilized to the peripheral
      blood. The purpose of this review is to give a recent update on the type and
      immunologic properties of CD34+ cells and CD34+ cell subsets mobilized by G-CSF
      or GM-CSF with emphasis on (1) relative efficacy of CD34+ cell mobilization; (2)
      relative toxicities of G-CSF and GM-CSF as mobilizing agents; (3) mobilization of
      dendritic cells and their subsets; (4) delineation of the role of adhesion
      molecules, CXC receptor 4, and stromal cell-derived factor-1 signaling pathway in
      the release of CD34+ cell to the peripheral blood after treatment with G-CSF or
      GM-CSF.

PMID- 11953662
TI  - Mechanisms of mobilization of hematopoietic progenitors with granulocyte colony
      stimulating factor.
AB  - Hematopoietic progenitor cells can be mobilized from the bone marrow to the blood
      by a wide variety of stimuli, including hematopoietic growth factors,
      chemotherapy, and chemokines. Increasingly, mobilized peripheral blood
      hematopoietic progenitor cells instead of bone marrow hematopoietic progenitor
      cells have been used to reconstitute hematopoiesis after myeloablative therapy
      because of their reduced engraftment times and relative ease of collection. A
      striking feature of hematopoietic progenitor cell mobilization is the ability of
      hematopoietic growth factors with distinct cellular targets and biologic
      activities to mobilize a similar spectrum of pluripotent and lineage-committed
      hematopoietic progenitor cells into the blood. Recent studies have identified
      some of the key adhesive interactions that regulate hematopoietic progenitor cell
      trafficking in the bone marrow. In addition, pathways linking mobilizing agents
      to hematopoietic progenitor cell mobilization have begun to be elucidated. This
      review summarizes these advances, emphasizing the mechanisms regulating
      granulocyte colony-stimulating factor-induced mobilization.

PMID- 11953664
TI  - Physiologic and pathologic consequences of granulocyte colony-stimulating factor
      deficiency.
AB  - Published studies have extended our understanding of granulocyte colony
      stimulating factor deficiency. In granulocyte colony-stimulating factor
      withdrawal in humans, apoptosis seems to account for the dramatic loss of
      neutrophils, but whether the apoptosis results from normal cellular aging
      processes or accelerated cell loss upon granulocyte colony-stimulating factor
      withdrawal is unclear. In granulocyte colony-stimulating factor(-/-) mice, the
      introduction of bcl-2, an antiapoptotic gene product, did not affect the number
      of neutrophils in the circulation. This finding suggests that apoptosis does not
      account for the lack of neutrophils in this setting and that the reduction in
      neutrophil numbers in these mice results from processes other than the loss of
      large numbers of granulocyte colony-stimulating factor-dependent cells after
      commitment to the neutrophil lineage. In an experimental model of the induction
      of antigranulocyte colony-stimulating factor antibodies, the animals appeared
      remarkably similar to granulocyte colony-stimulating factor(-/-) mice. This
      finding confirms that at least some neutrophils are produced by granulocyte
      colony-stimulating factor-independent mechanisms and suggests that the
      antigranulocyte colony-stimulating factor antibodies reported in clinical studies
      before and after granulocyte colony-stimulating factor administration do not lead
      to similar consequences. A gross loss of neutrophils as seen in these granulocyte
      colony-stimulating factor-immune mice has never been reported in patients,
      suggesting that such an occurrence is unlikely to have occurred.

PMID- 11953665
TI  - Hematopoietic growth factors, dendritic cell biology, and vaccine therapy of
      cancer.
AB  - Hematopoietic growth factors have made it possible to collect, manufacture, and
      engineer dendritic cells ex vivo for clinical use and expand dendritic cell
      subsets in vivo when administered to patients. Dendritic cells are important
      vectors in the induction of an effective immune response against infection and
      neoplastic disease. Antigens alone, even those preprocessed to bind to antigen
      presenting major histocompatibility complex class I and II molecules, are
      insufficient to regulate effective T-cell-mediated immunity. Activated dendritic
      cells are essential to this task. Studies of dendritic cell biology in the
      laboratory and preclinical studies have facilitated the implementation of
      clinical trials using dendritic cells in the treatment of melanoma and other
      cancers. Dendritic cell subset functional differences, effective tumor target
      antigen loading of dendritic cells for presentation to immune effector cells,
      dendritic cell maturation, the route of dendritic cell administration to humans,
      and immunologic monitoring are parameters that require vigorous study in the
      context of dendritic cell immunotherapy of cancer.

PMID- 11953666
TI  - Cost-benefit analysis of granulocyte colony-stimulating factor in the management
      of elderly cancer patients.
AB  - Health care costs continue to rise, and hospitalization represents the single
      largest component of direct medical costs associated with cancer care.
      Neutropenia and its complications including febrile neutropenia (FN) remain the
      major dose-limiting toxicity of systemic cancer chemotherapy. The risk of FN
      varies considerably across treatment regimens but appears to be significantly
      higher among elderly patients. The colony-stimulating factors (CSFs) have been
      used effectively in a variety of clinical settings to prevent or treat FN and to
      assist patients receiving dose-intensive chemotherapy with or without stem cell
      support. Several randomized controlled trials (RCTs) have demonstrated the
      clinical efficacy of the prophylactic use of CSFs. A recently presented meta
      analysis of the available RCTs has confirmed the efficacy of prophylactic CSFs.
      The cost of these agents, along with their large-scale clinical use, has prompted
      a number of economic investigations. Economic models based on measures of
      resource utilization derived from RCTs have provided FN risk threshold estimates
      for the cost-saving use of prophylactic CSF. A number of important studies
      concerning the clinical and economic impact of these agents in elderly cancer
      patients have been reported during the past year. Continuing clinical and
      economic evaluation along with an updating of clinical practice guidelines
      especially related to elderly patients is recommended because of rapid
      technologic and clinical advances.

PMID- 11953667
TI  - Antibiotics and growth factors in the management of fever and neutropenia in
      cancer patients.
AB  - The association of neutropenia and infection continues to be a major cause of
      morbidity and mortality in cancer patients receiving myelosuppressive
      chemotherapy. Prompt hospitalization and initiation of empirical intravenous
      broad-spectrum antibiotics has been the standard of care during the past three
      decades. Recently, risk-assessment models have been developed that allow the
      identification of febrile neutropenic patients that are at low risk for medical
      complications and mortality. New treatment strategies are being evaluated in this
      low-risk patient population to safely reduce toxicity, decrease costs, and
      improve quality of life. These include early shift from intravenous therapy to
      oral antibiotics, immediate initiation of oral empiric treatment, early hospital
      discharge, or outpatient care. A risk-based approach should also be applied to
      the use of colony-stimulating factors in this setting. Growth factors should not
      be routinely administered to neutropenic patients with uncomplicated febrile
      episodes. However, recent data support their use in populations with high-risk
      neutropenic fever.

PMID- 11953668
TI  - Clinical applications of hematopoietic growth factors in pediatric oncology.
AB  - Myeloid growth factors are widely used in both pediatric and adult oncology.
      Although the literature supporting the use of growth factors in pediatric
      oncology is less extensive than the adult literature, some uses are clearly
      established. Both granulocyte colony-stimulating factor and granulocyte
      macrophage colony-stimulating factor shorten the duration of febrile neutropenia
      after myelosuppressive chemotherapy, effectively mobilize hematopoietic stem
      cells for transplantation, and enhance neutrophil engraftment after hematopoietic
      stem cell transplantation. Although some open-label, uncontrolled trials and
      retrospective analyses support growth factor use to ameliorate the number of
      infections, duration of hospitalizations, and duration of intravenous antibiotic
      use after myelosuppressive chemotherapy or to enhance dose intensity, randomized
      controlled trials supporting these practices are lacking.

PMID- 11953669
TI  - Applications of darbepoietin-alpha, a novel erythropoiesis-stimulating protein,
      in oncology.
AB  - Darbepoietin-alpha is a novel erythropoiesis-stimulating protein that may help
      address some of the unmet needs of anemia treatment in patients with cancer.
      Compared with recombinant human erythropoietin, darbepoietin-alpha has increased
      sialylated carbohydrate content, associated with a prolonged serum half-life and
      increased in vivo biologic activity. Data from trials in patients with cancer
      with a range of tumor types, whether receiving chemotherapy or not, indicate that
      darbepoietin-alpha is effective in alleviating anemia when dosed at intervals of
      once every 1, 2, or 3 weeks and may effect greater and more rapid responses than
      recombinant human erythropoietin. Health-related quality of life benefits have
      been observed with darbepoietin-alpha treatment, and in a study of patients with
      small-cell lung cancer, darbepoietin-alpha was associated with increased
      progression-free survival. Administration of darbepoietin-alpha at extended
      dosing intervals offers the possibility of enhanced patient convenience and
      compliance and a reduced burden on healthcare resources. Confirmation of improved
      response and response times with this novel therapy may enable patients with
      cancer to benefit more rapidly.

PMID- 11953672
TI  - Penile surgery and reconstruction.
AB  - This review will highlight recent advances in the field of penile reconstructive
      surgery in the paediatric and adult population. It is based on the work published
      during the year 2001. Besides the anatomical and histological studies of the
      penis, major contributions have been described in congenital and acquired penile
      anomalies. Also, a few new techniques and modifications of old procedures are
      described in order to improve the final functional and aesthetic outcome. The
      techniques for penile enlargement present a trend in the new millennium, but are
      still at the stage of investigation.

PMID- 11953670
TI  - Methods and progress in assessing the quality of life effects of supportive care
      with erythropoietin therapy.
AB  - Anemia is a common disorder in patients with cancer and can be caused by the
      disease itself or by cancer-related therapy. The cardinal symptom of anemia,
      fatigue, is the most commonly reported symptom in patients with cancer and has
      profound effects on patient well-being and quality of life. Until recently, blood
      transfusions were the mainstay of management of cancer-related anemia, despite
      attendant risks of transfusion-related reactions and transmission of infection.
      Recombinant human erythropoietin (epoetin-alpha), an effective alternative to
      blood transfusion, has been shown to improve hematologic parameters, including
      hemoglobin levels, Hematocrit, and transfusion requirements. Clinical trials have
      also suggested that this intervention has a positive impact on the quality of
      life of patients with cancer. The literature published between November 2000 and
      October 2001 continues to support a positive effect of epoetin-alpha therapy on
      the quality of life of patients with cancer and includes investigations of dosing
      schedules more convenient for patients and trials of longer-acting versions of
      epoetin-alpha, such as the novel erythropoiesis-stimulating protein. Future
      studies that incorporate measures of patient-reported outcomes and rigorous
      methodologic designs are needed to strengthen and elucidate this association
      between these pharmacologic therapies for cancer-related anemia and quality of
      life.

PMID- 11953673
TI  - Hypospadias and bladder exstrophy.
AB  - Reconstructive surgery for patients with hypospadias, bladder exstrophy and
      cloacal exstrophy is challenging. Over the last few years, more and more data
      have become available concerning incidence and epidemiology, as well as short-
      and long-term results of surgical techniques. The tubularized incised plate
      urethroplasty for hypospadias repair continues to gain in popularity. However,
      the results of long-term studies of larger series supporting this enthusiasm are
      still missing. Buccal mucosa is more frequently used in complex hypospadias cases
      with good short- and long-term results. The one-stage approach of exstrophy
      repair seems to be promising. However, failures, which require very complex
      reconstructions, are also reported. Urodynamic studies demonstrated severe
      abnormalities of bladder function even in continent patients. Therefore, one must
      question the normality of voiding patterns, and the price to be paid in achieving
      continence for patients with exstrophy. Achievement of continence for urine and
      stool is possible for patients with cloacal exstrophy. The colon should be
      preserved and should not be used for bladder or vaginal reconstruction. The
      incidence of neoplasia in patients with bladder exstrophy seems to be higher than
      expected. However, only one cohort study is presently available.

PMID- 11953674
TI  - Bladder reconstruction: urothelial augmentation, trauma, fistula.
AB  - Urothelial augmentation in the form of augmentation enterocystoplasty continues
      to be the mainstay of surgical treatment for neuropathic bladder dysfunction and
      detrusor instability. The outcome of the procedure is satisfactory, but a number
      of complications are becoming more clearly defined. Computed tomography
      cystography is now the investigation of choice for diagnosing bladder rupture.
      The indications for computed tomography cystography are discussed. The current
      management of enterovesical fistula is reviewed.

PMID- 11953675
TI  - Functional reconstruction and minimally invasive techniques.
AB  - Recent years have seen notable advances in imaging technologies. Three
      dimensional computer-rendered techniques with rapid image acquisition have led to
      the development of virtual reality imaging. Virtual reality imaging allows
      interactive intraluminal navigation through any hollow viscus, simulating
      conventional endoscopy. This technique of virtual endoscopy has been applied to
      many organs, including the urinary tract. Virtual reality endoscopy is beginning
      to challenge the gold standard of conventional endoscopic evaluation. Recent
      advances in laparoscopic surgery are largely attributable to technological
      improvements in imaging equipment. Laparoscopic ultrasound has become a common
      adjunct in laparoscopic surgery. In particular, advances in video cameras and
      digital imaging technology have decreased the steep learning curve associated
      with laparoscopic procedures. Telerobotic systems offer several advantages to
      laparoscopic surgery, such as all six degrees of freedom, dexterity enhancement,
      tremor filtering, and stereovision. In addition, technological breakthroughs
      allow many procedures to evolve from open operations involving lengthy hospital
      stays to imaging-guided minimally invasive procedures performed on an outpatient
      basis. Finally, Internet-based imaging is changing the way in which urology
      services are delivered, by allowing rapid communication between remote locations.

PMID- 11953676
TI  - Simulators and endourological training.
AB  - Acquisition of skills laboratory training seems to be of importance in the
      training of surgeons, and is intended to cover the gap between theoretical
      learning and real practice. Economic and ethical reasons limit the use of animals
      during the learning process, while trends in medical change have severely
      restricted the available time to teach and to learn. With the incorporation of
      laparoscopy and the blossoming of minimally invasive techniques, mainly
      endoscopy, simulators have gained wide acceptance as an important tool in the
      surgeon's learning process. Two types of simulators are currently available:
      inanimates or mannequins and virtual reality simulators. A review of the recent
      literature shows that there is generally a significant improvement in dexterity
      after using simulators, whichever type is used. It is still unknown whether
      training simulation influences the patient's outcome positively.

PMID- 11953677
TI  - Ureteral stents and their use in endourology.
AB  - Ureteral stents have assisted urologists in the performance of surgery of the
      urinary tract for many years. They can have both diagnostic and therapeutic
      value, but are used most frequently as adjuncts to endoscopic or minimally
      invasive procedures. This review provides an update of the current uses for
      ureteral stents, technology of biomaterials, complications associated with
      indwelling ureteral stents and the future of stents in urology.

PMID- 11953678
TI  - Which urethroplasty for which results?
AB  - PURPOSE OF REVIEW: Urethral surgery is rapidly changing because of developments
      in techniques. The aim of this paper is to provide an update and a review of the
      most significant surgical options and their outcomes in the treatment of urethral
      strictures. RECENT FINDINGS: Indications and results of anastomotic repair,
      pedicled flap, free graft and complex urethral reconstruction are reported. New
      trends such as dorsal urethroplasty and the use of buccal mucosa are reviewed.
      SUMMARY: Most urethral strictures can be managed successfully by urethral
      surgery. A wide spectrum of effective procedures is available. To obtain optimal
      results, adequate knowledge and experience of the most common techniques are
      required.

PMID- 11953679
TI  - Hand-assisted laparoscopic nephrectomy.
AB  - Hand-assisted surgery enjoys the benefits of open surgery while maintaining the
      post-operative advantages of laparoscopy. Logical indications for its application
      largely include those cases that require removal of a large amount of tissue
      intact. Hand-assisted laparoscopic surgery may find application in complex
      procedures such as radical, partial and difficult nephrectomies.

PMID- 11953680
TI  - Hand-assisted urological laparoscopy.
AB  - Hand-assisted laparoscopy has been successfully applied to various applications
      within the field of urology. Many authors have proved the safety and efficacy of
      this technique, as well as demonstrating improved patient recovery for such
      procedures as radical nephrectomy, radical nephroureterectomy and donor
      nephrectomy. The recent literature regarding this topic is reviewed and evaluated
      here.

PMID- 11953681
TI  - New diagnostic and prognostic tools in bladder cancer.
AB  - Many efforts have been made to increase the detection rates and to predict the
      outcome of bladder cancer. Although to date cystoscopy remains the gold standard
      method for the detection of new or recurrent bladder cancer, its limitations were
      emphasized by the results of studies using fluorescence endoscopy that showed an
      increased detection rate and decreased recurrence after tumor resection. Urine
      cytology has high specificity and is used routinely as an adjunct to cystoscopy
      to detect invisible tumors. However, to improve on the low sensitivity of urine
      cytology, a number of marker tests have been developed. Optimal diagnostic
      accuracy appears to result from the synergistic combination of cytological
      markers with urine cytology. The evaluation of new and previously reported
      markers remains a very active field, but is still limited to inconclusive
      studies. Tissue and DNA microarrays represent a technological step forward for
      the analysis of a large number of markers and cohorts of patients that will be
      required definitively to establish the clinical utility of prognostic tests.

PMID- 11953682
TI  - Impact factors: uses and abuses.
AB  - Quantitative assessment of the scientific merit of journals and articles is being
      used increasingly to assess and compare researchers and institutions. The most
      commonly used measure is the 2 year Impact Factor, which broadly reflects the
      number of times each article in the journal has been cited over the previous 2
      years. There are clear limitations to the use of such measures - not least,
      Impact Factors reflect the journal not the article, vary with time and correlate
      only poorly with perceived excellence. Simple comparison of impact factors in
      different specialties may be misleading. Review journals often have higher Impact
      Factors than those with original data. Both authors and editors can try to
      manipulate journal Impact Factors. However, despite valid concerns, Impact
      Factors are widely used and offer, at present, the best simple tool for
      comparison of output. Like all measures, the use of Impact Factors has to be
      tempered with knowledge of their limitations and common sense used in
      interpreting any data based on any analysis.

PMID- 11953683
TI  - The UDCA dosage deficit: a fate shared with CDCA.
AB  - Ursodeoxycholic acid (UDCA) is used both as the treatment of choice in many
      cholestatic syndromes and as complementary therapy in many liver diseases.
      However, few dose-finding studies exist, and none has evaluated the efficacy and
      long-term safety of UDCA therapy in primary biliary cirrhosis (PBC). There is an
      open debate about UDCA's impact on the natural history of PBC, and no universal
      evidence of benefits on the major endpoint exists. This is perhaps due to a UDCA
      dosage deficit. Most clinical trials on PBC therapy have used conservative
      dosages of UDCA similar to those of chenodeoxycholic acid (CDCA) used for
      dissolution of gallstones. It may be necessary to re-evaluate the dosage of UDCA
      that provides the most effective treatment.

PMID- 11953684
TI  - Strategies for early diagnosis of haemochromatosis.
AB  - Genetic haemochromatosis is one of the most frequent inborn errors of metabolism.
      Only patients with early non-cirrhotic haemochromatosis treated by phlebotomies
      have a normal life expectancy. The present review analyses strategies for early
      diagnosis of haemochromatosis by using the Medline database and own data from a
      large cohort of patients with haemochromatosis. The still widely used approach to
      look for haemochromatosis in the presence of clinical complications such as liver
      disease will detect haemochromatosis in a considerable percentage of patients
      with Celtic origin. However, up to one half of these patients will already have
      an irreversible complication such as liver cirrhosis, diabetes mellitus or
      cardiomyopathy. In contrast, screening approaches of non-selected asymptomatic
      subjects using either determination of transferrin saturation and serum ferritin
      (phenotypic screening) or using genetic testing will detect haemochromatosis in
      most subjects in a precirrhotic stage without irreversible complications. Both
      phenotypic and genetic screening are highly cost-effective for detection of iron
      loaded individuals in the general population. The current clinical approach to
      look for haemochromatosis in the presence of clinical disease is unacceptable.
      Only a more general type of screening in asymptomatic subjects including genetic
      testing will increase the rate of early diagnosis and will further improve the
      clinical outcome.

PMID- 11953685
TI  - Testing for haemochromatosis in a liver clinic population: relationship between
      ethnic origin, HFE gene mutations, liver histology and serum iron markers.
AB  - OBJECTIVE: To identify the most appropriate testing strategy for genetic
      haemochromatosis in a liver clinic population by determining the ethnic
      distribution of the HFE mutations and the relationship between serum iron
      markers, hepatic siderosis and HFE genotype. DESIGN AND SETTING: Observational
      study of 427 patients being investigated for abnormal liver function tests
      between 1997 and 2000 attending a liver clinic at a teaching district general
      hospital in south London, UK. METHODS: All patients were tested for H63D and
      C282Y gene mutations, and the ethnic origin was determined. Data were available
      for most patients for non-fasting serum iron, ferritin and transferrin saturation
      on presentation and fibrosis and siderosis scores from liver biopsy. RESULTS: The
      C282Y mutation was not detected in any patients of Asian or Afro-Caribbean origin
      but was found almost exclusively in northern Europeans, especially those
      classified as Celtic, one in seven of whom were heterozygous for this mutation.
      Three per cent of all the patients tested were C282Y homozygotes. The H63D
      mutation was distributed more widely. An elevated serum transferrin saturation
      was both a more sensitive and a more specific test for genetic haemochromatosis
      than either serum ferritin or iron. Significantly raised mean siderosis scores
      were found on liver biopsy in C282Y homozygote and C282Y/H63D compound
      heterozygote groups but not in wild-type, simple heterozygote, or H63D homozygote
      groups. Forty-five per cent of the C282Y homozygotes detected already had
      cirrhosis. CONCLUSIONS: In a multiracial liver clinic population, previously
      undiagnosed C282Y homozygosity was found to be common (3% in our study) but
      restricted to those of northern European heritage, particularly those with Celtic
      ancestry. A serum transferrin saturation proved a better initial test to select
      patients for genotyping than serum iron or ferritin. Laboratory costs can be
      minimized with no loss of diagnostic sensitivity by selecting patients for
      genotyping based on northern European ethnic origin and raised serum transferrin
      saturation.

PMID- 11953686
TI  - Colorectal disease in liver allograft recipients -- a clinicopathological study
      with follow-up.
AB  - OBJECTIVE: To determine the spectrum and outcome of colorectal diseases occurring
      in adult liver allograft recipients. DESIGN: A retrospective cohort analysis of
      clinical, microbiological and histopathological data regarding colorectal
      disease. PATIENTS: Forty three out of 302 adult primary liver allograft
      recipients were transplanted and followed up (at median 42 months) at a tertiary
      referral centre/teaching hospital. RESULTS: Out of 302 patients, 43 (14%) were
      investigated (by endoscopy and/or laparotomy) for symptoms of colorectal disease
      after orthotopic liver transplantation. The symptoms were: diarrhoea (n = 31);
      per-rectal bleeding (n = 5); and symptoms relating to pre-transplant ulcerative
      colitis (n = 7). Among the patients without known ulcerative colitis, per-rectal
      bleeding occurring early after orthotopic liver transplantation was most commonly
      caused by cytomegalovirus colitis and carried a poor prognosis. Excluding
      ulcerative colitis, the commonest causes of diarrhoea were Clostridium difficile,
      cytomegalovirus infection and medications, particularly during the first 2 months
      after orthotopic liver transplantation. No cases of colorectal graft-versus-host
      disease, cryptosporidiosis, amoebiasis, atypical mycobacterial infection or post
      transplant lymphoproliferative disease were demonstrated. The activity of pre
      transplant ulcerative colitis was unchanged or increased after orthotopic liver
      transplantation. Two further patients developed new-onset ulcerative colitis
      after orthotopic liver transplantation. CONCLUSIONS: Ulcerative colitis, C.
      difficile, cytomegalovirus infection and medications are the commonest colorectal
      causes of morbidity after orthotopic liver transplantation. Adult liver allograft
      recipients are, however, unlikely to show certain large bowel diseases
      encountered in other immunosuppressed groups. Amongst non-ulcerative colitis
      patients, those presenting with diarrhoea show a good outcome with appropriate
      management, whereas those with per-rectal bleeding have a more guarded prognosis.

PMID- 11953687
TI  - The role of CD40 in ulcerative colitis: histochemical analysis and clinical
      correlation.
AB  - OBJECTIVES: CD40 co-stimulator seems to be implicated in the loss of tolerance
      against self-antigens in many autoimmune diseases. The evidence suggests that in
      the pathogenesis of ulcerative colitis there is an activity state against self
      antigens of the gut wall and flora. The aim of this study was to analyse the
      expression of CD40 in ulcerative colitis, comparing it with Crohn's disease and
      nonspecific inflammation of the colon and to determine whether there is a
      relationship between its expression and the activity stage of the disease.
      METHODS: The expression of CD40 in the colonic samples of 51 patients (30
      ulcerative colitis, 9 Crohn's disease and 12 nonspecific inflammation) was
      analysed by immunohistochemistry. Twenty-four patients with ulcerative colitis
      were scored according to clinical, endoscopic and histological classification.
      RESULTS: The mean percentage of CD40+ cells per field in the colonic mucosa was:
      ulcerative colitis 21 +/- 11%, Crohn's disease 24 +/- 9%, nonspecific
      inflammation 7 +/- 7%. The ulcerative colitis patients were statistically
      significantly different compared to the patients with nonspecific inflammation (P
      < 0.005), even when comparing the patients in remission (P < 0.05). The
      expression in Crohn's disease was similar to that in ulcerative colitis. The
      expression of CD40 in ulcerative colitis was directly proportional to the state
      of activity of the disease according to the clinical (P < 0.02), endoscopic (P <
      0.01) and histological (P < 0.02) criteria. CONCLUSIONS: The expression of CD40
      in the colonic mucosae of patients with ulcerative colitis is significantly
      increased and is proportional to the state of activity. The results seem to
      confirm the hypothesis that a loss of tolerance could be involved in the
      pathogenesis of this disease.

PMID- 11953689
TI  - Coagulation factor XIII and markers of thrombin generation and fibrinolysis in
      patients with inflammatory bowel disease.
AB  - OBJECTIVE: To relate factor XIII levels and other prothrombotic markers to
      inflammatory bowel disease and investigate the frequency of valine34leucine and
      its effect on factor XIII cross-linking activity in patients with inflammatory
      bowel disease. DESIGN: Fifty patients with active inflammatory bowel disease but
      no venous thromboembolism (32 with ulcerative colitis, 18 with Crohn's disease),
      50 patients with inactive inflammatory bowel disease but no venous
      thromboembolism (32 with ulcerative colitis, 18 with Crohn's disease), two age-
      and gender-matched healthy control groups of 100 subjects each were recruited. To
      further explore the relationship between valine34leucine and inflammatory bowel
      disease, 21 patients with the disease (13 with ulcerative colitis and eight with
      Crohn's disease) and venous thromoembolism (male to female ratio = 7 : 14, median
      age 59.5 years (range, 19-80 years)) were recruited. Two hundred and fifteen
      control subjects (M : F = 121 : 94, median age 62 years (28-74 years)), with
      venous thromboembolism (119 with deep venous thrombosis, and 96 with pulmonary
      embolism) were drawn from the same geographical area as the patients. METHODS:
      Factor XIII A, B-subunit antigen and A2B2 tetramer levels were measured using an
      in-house sandwich enzyme-linked immunoassay method. RESULTS: Factor XIII A2B2
      tetramer and the A-subunit were significantly decreased in patients with active
      inflammatory bowel disease compared with controls (59% vs 95%, P < 0.0001 and 75%
      vs 102%, P < 0.0001, respectively), but not between the inactive inflammatory
      bowel disease group and controls. The D-dimer and prothrombin 1+2 fragment levels
      in patients with active inflammatory bowel disease were raised compared with
      controls (178 (152) vs 109 (84), P = 0.0007 and 82 (43) vs 55 (28), P = 0.0001,
      respectively). The factor XIII B-subunit and factor XIII cross-linking activity
      were not significantly different between patients with active or inactive
      inflammatory bowel disease and controls. There was no significant difference in
      genotype distribution in inflammatory bowel disease patients with or without
      venous thromboembolism and respective control subjects. Levels of tissue
      plasminogen activator antigen were significantly increased in patients with
      active inflammatory bowel disease when compared to inactive inflammatory bowel
      disease and controls (8.9 (3.7) vs 6.7 (3.4) vs 6.9 (3.4), P < 0.001).
      CONCLUSIONS: Active inflammatory bowel disease is associated with activation of
      coagulation. Factor XIII A and A2B2 tetramer levels were markedly decreased in
      active inflammatory bowel disease. Variations in the level of factor XIII in
      patients with inflammatory bowel disease could be multifactorial and in part may
      result from the increased formation of microthrombi and accelerated turnover of
      the factor XIII. We found no evidence of association of factor XIII
      valine34leucine polymorphism and inflammatory bowel disease.

PMID- 11953688
TI  - Octreotide in patients with active ulcerative colitis treated with high dose
      corticosteroids (OPUS 1).
AB  - BACKGROUND: In ulcerative colitis the intestinal somatostatin content is reduced.
      Somatostatin has several immune-inhibitory effects. In vitro it diminishes
      activity of intestinal lymphocytes and peripheral blood monocytes. Its long
      acting analogue octreotide has beneficial effects on mucosal damage in acute
      experimental acetic acid colitis in rats. AIMS: To determine the potential
      benefits of octreotide as a treatment for patients with severe ulcerative colitis
      treated with high dose corticosteroids. PATIENTS: Forty-two patients with severe
      ulcerative colitis (more than 10 points on the Powell-Tuck scoring system and
      mucosal disease Heatly grade III or IV). METHODS: In a multi-centre, double
      blind, placebo-controlled trial all patients were treated with oral 5-ASA (1.6
      2.4 g daily) and high dose corticosteroids (tapering off from 60 to 80 mg daily).
      They were randomly assigned to receive subcutaneous placebo (n = 22) or
      octreotide 500 microg (n = 20) thrice daily during 21 days. Clinical and
      endoscopic disease activity, histology and laboratory parameters were obtained
      during the study period. RESULTS: Clinical disease activity for both octreotide
      and placebo were not significantly different at baseline and after 21 days of
      treatment. Endoscopic disease activities (mean +/- SD) changed from 12.5 +/- 4.7
      to 7.2 +/- 5.3 for octreotide, and from 11.5 +/- 5.0 to 5.0 +/- 3.4 for placebo
      (NS). Seven patients from both groups received additional treatment (colectomy (n
      = 6), cyclosporin (n = 1)). Adverse events occurred equally in both groups.
      CONCLUSIONS: Subcutaneous administration of octreotide 500 microg thrice daily is
      not of additional benefit as adjuvant therapy to high dose corticosteroids in
      severe ulcerative colitis.

PMID- 11953690
TI  - A test-and-treat policy does not save endoscopy workload in a non-referral
      hospital.
AB  - AIM: To assess the impact that a test-and-treat policy with open-access urea
      breath testing (UBT) has had on the referral rates for endoscopy in a district
      hospital. Additionally, we examined for any change in the proportion of serious
      pathology detected endoscopically after adopting the policy. METHODS: Analysis of
      data on all open-access endoscopy referrals in a 12-month period before (October
      1994 to September 1995) and 2 years after (October 1997 to September 1998) the
      introduction of the UBT service. This was compared with the same service in our
      sister hospital, which had not provided a UBT service. Results of patients
      attending the UBT service during the period of study were also examined. RESULTS:
      A total of 798 patients attended for endoscopy (18% aged < 40 years, 82% aged >
      40 years) in the pre-UBT year compared with 1905 patients (16% aged < 40 years,
      84% aged > 40 years) in the post-UBT year. The standardized referral ratios were
      significantly higher for both age groups in the post-UBT year: 210 in the < 40
      years group (95% CI 187 to 235) and 244 in the > 40 years group (95% CI 233 to
      257). Six per cent of the < 40 years group in the post-UBT year had serious
      pathology compared with 7% pre-UBT (P < 0.1). However, the proportion of serious
      pathology decreased from 37 to 27% in the > 40 years group (P < 0.01). The total
      number of open-access endoscopies had increased steadily over the 3 years,
      despite the introduction of the UBT service. This trend was mirrored in our
      sister hospital. A total of 457 patients attended the UBT service during the 12
      months. Of these, 24.5% were Helicobacter pylori positive, with a 66.3%
      eradication rate. CONCLUSIONS: A test-and-treat policy has not saved endoscopy
      workload in this non-referral hospital. We feel that results from centres with an
      H. pylori interest cannot be generalized for the vast majority.

PMID- 11953691
TI  - Effects of endoscopic variceal treatment on oesophageal function: a prospective,
      randomized study.
AB  - AIM: Endoscopic methods are currently the most widely used techniques for the
      treatment of bleeding oesophageal varices (BOV). However, a number of
      complications may limit their usefulness. We conducted a prospective, randomized
      comparison of variceal ligation versus sclerotherapy in cirrhotics after the
      control of variceal haemorrhage to study the relative short-term risks of these
      two procedures with respect to oesophageal motility and gastro-oesophageal
      reflux. METHODS: Seventy-three patients with established cirrhosis and an episode
      of variceal bleeding controlled by one session of endoscopic therapy were
      randomized to treatment with sclerotherapy or ligation until variceal
      eradication. In 60 of these patients, oesophageal manometry and 24-h intra
      oesophageal pH monitoring were performed at inclusion and 1 month after variceal
      eradication. RESULTS: After variceal eradication with sclerotherapy, peristaltic
      wave amplitude decreased from 76.2 +/- 14.7 mmHg to 61.6 +/- 17.7 mmHg (P =
      0.0001), simultaneous contractions increased from 0% to 37.9% (P = 0.0008), and
      the percentage of time with pH < 4 increased from 1.60 +/- 0.25 to 4.91 +/- 1.16%
      in channel 1 (P = 0.0002) and from 1.82 +/- 0.27 to 5.69 +/- 1.37% in channel 2
      (P = 0.0006). In contrast, the above parameters were not disturbed with ligation.
      CONCLUSION: Our data define the advantages of ligation over sclerotherapy with
      respect to post-treatment oesophageal dysmotility and associated gastro
      oesophageal reflux.

PMID- 11953692
TI  - Oesophageal motor and sensitivity abnormalities in non-obstructive dysphagia.
AB  - OBJECTIVES: To evaluate oesophageal sensitivity to balloon distension in patients
      with non-obstructive dysphagia (NOD), and to determine its relationship with the
      motility pattern in response to food ingestion. PATIENTS AND METHODS: Twenty-one
      healthy volunteers and 19 consecutive patients complaining of NOD with normal
      standard manometry were included. An oesophageal sensitivity test was carried out
      before the manometry study with liquid and solid swallows. RESULTS: The median
      threshold to distension was 9 ml in control subjects and 5 ml in patients (P <
      0.002). Dysphagia or odynophagia were reproduced in 15/19 (78.9%) patients during
      manometry with solid swallows only. The percentage of swallows with abnormal
      motility patterns was higher in patients than control subjects (P < 0.001).
      Compared with control values, sensitivity abnormality was defined by a distension
      threshold of < 6 ml. Motor abnormality was defined by > 19% of swallows occurring
      with one or more abnormal motor profiles. A total of 8/19 (42%) patients
      presented with the association of an abnormal sensitivity threshold and an
      abnormal motor pattern; 5/19 (26%) presented with isolated motor abnormalities;
      4/19 (21%) patients presented with isolated abnormal sensitivity thresholds; and
      2/19 (11%) patients presented without any abnormality. CONCLUSION: Manometry with
      solid swallows and oesophageal balloon distension are useful in characterizing
      NOD.

PMID- 11953693
TI  - Heartburn in Belgium: prevalence, impact on daily life, and utilization of
      medical resources.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a frequently occurring
      disease that may be considered a public health issue, particularly in developed
      countries. The specificity of heartburn for the diagnosis of GORD is good. Our
      aim was to define the prevalence of heartburn in Belgium, characterizing both its
      impact on everyday life and the ensuing use of medical resources. METHODS: Two
      thousand people living in Belgium, selected randomly after stratification, were
      interviewed face to face. The main question in the questionnaire used in this
      interview concerned the presence over the previous 12 months of a burning
      sensation in the epigastric and/or retrosternal region. This was followed by 21
      secondary questions on the characteristics of the population studied, the impact
      of heartburn on everyday life, and the medical resources used. RESULTS: Twenty
      eight per cent of the population interviewed reported heartburn. This symptom was
      present at least once a week in 42% of sufferers. Heartburn was more frequent in
      women than men (P < 0.05) and was not distributed uniformly throughout the
      various regions of the country (P < 0.05). Seventy-seven per cent of the people
      with heartburn found that it had a significantly negative impact on their daily
      lives (in 27%, this effect was strong). Heartburn associated with a substantial
      negative impact on daily life was characterized by a higher frequency of symptoms
      (P < 0.0001), a longer duration of the problem (P = 0.006), and the presence of
      pain (P < 0.0001) and anxiety (P < 0.0001). Fifty-six per cent of individuals
      with heartburn had already sought medical advice, 45% had undergone an upper
      gastrointestinal tract endoscopy, and 59% were taking medications. Among patients
      complaining that heartburn had a substantial negative effect on their everyday
      lives, 21.6% had not sought medical advice and 22.2% did not take any medication.
      CONCLUSION: Heartburn is very frequent in Belgium and is associated with a
      considerable negative impact on everyday life. It also generates a significant
      use of medical resources. However, among the patients complaining of a
      substantial negative effect on their daily lives, one-fifth (which would
      represent 1.5% of the Belgian population) seemed to lack appropriate care.

PMID- 11953694
TI  - Achalasia treatment in the elderly: is botulinum toxin injection the best option?
AB  - BACKGROUND: Achalasia treatment in elderly patients is a matter of controversy.
      Botulinum toxin injection has been proposed as the best option in this group of
      patients as it is a safe procedure. However, concern persists regarding its short
      term effect. AIMS: To analyse the clinical and economic effectiveness of
      botulinum toxin injection in the treatment of achalasia patients who are elderly.
      METHODS: Seventeen consecutive achalasia patients older than 65 years were
      treated with 80 units of botulinum toxin. Clinical follow-up at 1, 6 and 12
      months was performed. Control manometry when symptoms recurred was carried out.
      Results were compared with those of an historical control group of 16 achalasia
      patients also older than 65 years and who had been treated with endoscopic
      dilation. The costs of both procedures were compared. RESULTS: Twenty-nine
      botulinum toxin injections were performed in the 17 patients of the botulinum
      toxin group (follow-up, 12-36 months). In the dilation group only two patients
      had to be retreated (follow-up, 12-108 months). No major complications were
      observed in either group. The average duration of symptom alleviation was 48 +/-
      33 months for endoscopic dilation and 13.8 +/- 9.5 months for botulinum toxin
      injection. Maintaining a patient free of symptoms cost E348.31 per year for
      botulinum toxin injection, whilst if endoscopic dilation was chosen the cost was
      only E117.47 per year. CONCLUSIONS: The effect of botulinum toxin injections
      wanes with time in elderly patients, necessitating repeated injections to keep
      the patients symptom-free. Due to the required repeated injections this procedure
      is more expensive than endoscopic dilation.

PMID- 11953695
TI  - Relation between alcohol consumption and the success of Helicobacter pylori
      eradication therapy using omeprazole, clarithromycin and amoxicillin for 1 week.
AB  - OBJECTIVE: To study the relationship between daily alcohol consumption and the
      result of eradication therapy for Helicobacter pylori using omeprazole,
      clarithromycin and amoxicillin for 1 week. DESIGN: Clinical trial. SETTING: Urban
      health centre, general medicine section. PARTICIPANTS: One hundred and fifty-six
      patients with a diagnosis of peptic ulcus or chronic gastritis. Helicobacter
      pylori infection was confirmed by the urease test, the 14C-urea breath test, IgG
      serology or biopsy. INTERVENTIONS: A combination of omeprazole, 20 mg twice
      daily, clarithromycin, 500 mg twice daily, and amoxicillin, 1000 mg twice daily
      was administered for 1 week. No other drugs were given. Four to 8 weeks later a
      14C-urea breath test was carried out to confirm eradication. MAIN OUTCOME
      MEASURES: Logistic regression was used to assess the relationship between
      eradication and daily alcohol consumption (main covariable), age, sex, smoking,
      length of illness, pathology studied (ulcus or gastritis) and therapeutic
      compliance. RESULTS: Eradication (intention to treat analysis) was successful in
      118 patients (75.6%; 95% CI, 68.9-82.4). The only variable significantly
      associated with the result of the therapy was daily alcohol consumption, with a
      higher probability of failure in non-consumers (29.9%) than in consumers (12.2%),
      adjusted OR 3.24 (95% CI, 1.12-9.20; P = 0.03). Eradication was dose dependent:
      70.1% in abstemious patients (n = 107), rising to 79.3% in users of 4-16 g of
      pure ethanol a day (n = 29) and to 100% in users of 18-60 g daily (n = 20) with a
      P value of 0.005 for the trend. CONCLUSIONS: Daily alcohol consumption appears to
      have an additive effect in this eradication therapy.

PMID- 11953697
TI  - Push enteroscopy in a UK district general hospital: experience of 51 cases over 2
      years.
AB  - OBJECTIVES: To determine the number of patients referred for enteroscopy in a
      district general hospital (DGH), the indication, enteroscopic +/- histological
      diagnosis, and to compare findings with other series from tertiary referral
      centres or outside the UK. DESIGN: Retrospective case series over a 2-year
      period. RESULTS: In the 2-year period, 52 patients were referred for enteroscopy.
      All except one underwent enteroscopy. The mean age of the patients was 60 years
      (range 31-84 years). The main indications for enteroscopy were obscure
      gastrointestinal haemorrhage in 31 (61%) patients (19 with acute and 12 with
      chronic bleeding) and 7 (14%) patients with arteriovenous malformations (AVMs) on
      initial oesophagogastroduodenoscopy (OGD). Other indications included clinical
      deterioration in known coeliac disease in four (8%) patients and abnormal small
      bowel follow-through in five (10%) patients. More than half (51%) of the
      enteroscopies were reported as abnormal, but 10 (38%) had pathology in the
      stomach or first part of the duodenum (D1) not diagnosed on initial OGD.
      Diagnoses of two T-cell lymphomas and one of pre-lymphomatous monoclonal T-cell
      proliferation were made in the refractory coeliac disease group. CONCLUSIONS:
      Indications (obscure gastrointestinal bleeding), most frequent findings (small
      bowel AVMs), and 'missed' lesions within reach of a gastroscope (20%) were in
      keeping with other series. Enteroscopy is a useful tool in investigating patients
      with refractory coeliac disease. Its value in investigating patients with
      abnormal small-bowel radiology was not confirmed. The current need for push
      enteroscopy in a DGH is small (approximately 1 per 8000 population per year), but
      it would take only small changes in referral practice to escalate. Criteria for
      enteroscopy should be developed and refined with improving knowledge of the
      diagnostic yield for each indication and clinical outcome.

PMID- 11953696
TI  - Reduced PTEN expression in gastric cancer and in the gastric mucosa of gastric
      cancer relatives.
AB  - OBJECTIVES: Gastric cancer is a leading cause of cancer-related deaths worldwide,
      and the genetic and molecular alterations underlying its pathogenesis are largely
      unknown. PTEN, a tyrosine phosphatase, is frequently mutated in brain and breast
      cancers but not in gastric cancers. In order to assess the role of PTEN in
      gastric carcinogenesis, we analysed the expression of PTEN in human gastric
      cancer and in the gastric mucosa of cancer relatives. METHODS: Gastric cancer
      tissues were obtained from 26 patients with gastric cancer undergoing upper
      gastrointestinal endoscopy or resection for gastric cancer. Furthermore, 21 first
      degree relatives of gastric cancer patients and 12 healthy individuals agreed to
      undergo upper-gastrointestinal endoscopy. In all cases, biopsies were taken from
      the antrum and corpus. PTEN expression was assessed by semiquantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) analysis and
      immunohistochemistry. RESULTS: PTEN expression was reduced or absent in 21/26
      gastric cancers compared with the matched non-malignant gastric biopsy (P <
      0.001). Furthermore, PTEN expression was reduced significantly in the antrum
      biopsy of first-degree relatives compared with healthy controls (P < 0.05).
      CONCLUSIONS: Reduced expression of PTEN in gastric cancer points to another
      mechanism apart from PTEN mutation that may be involved in the pathogenesis of
      gastric cancer. The reduction of PTEN expression was also observed in first
      degree relatives.

PMID- 11953698
TI  - IgA-class transglutaminase antibodies in evaluating the efficacy of gluten-free
      diet in coeliac disease.
AB  - OBJECTIVE: Serum IgA-class tissue transglutaminase antibody has proved effective
      in screening for coeliac disease. The response to a gluten-free diet has been
      assessed on the basis of small-intestinal morphology. We investigated whether the
      tissue transglutaminase antibody test could substitute biopsy in this respect,
      and whether the test is better than the endomysial antibody test in follow-up.
      DESIGN: Controlled cross sectional, and follow-up study. METHODS: Serum IgA-class
      tissue transglutaminase antibodies and endomysial antibodies were determined in
      87 coeliac adults on a gluten-free diet. All underwent small bowel biopsy, and
      the mucosal morphology was interpreted along with Marsh's grading 0-3. In 30
      patients histological and serological data could be analysed before and after
      adopting the diet; Marsh 3 was considered inadequate mucosal recovery during the
      diet. RESULTS: Of the 87 coeliac patients 27 showed Marsh 3 villous atrophy on
      gluten-free diet; of these 27, tissue transglutaminase antibody was within normal
      limits in 16 (59%) and endomysial antibody in 20 (74%). Two (7%) out of 29 with
      normal mucosa (Marsh 0) had positive tissue transglutaminase antibodies. Six
      (55%) out of 11 admitting regular dietary lapses remained tissue transglutaminase
      antibody negative. In the follow-up, serum IgA-class tissue transglutaminase
      antibody was initially positive in 28 (93%) out of 30 untreated patients; even a
      significant decrease in tissue transglutaminase antibody did not guarantee
      mucosal recovery. CONCLUSIONS: A substantial number of coeliac patients with
      negative tissue transglutaminase or endomysial antibodies may still have manifest
      mucosal villous atrophy. Small bowel biopsy is therefore still necessary to
      ensure that the gluten-free diet is adequate.

PMID- 11953699
TI  - Translating vague complaints into precise symptoms: the implications of a poor
      medical history.
AB  - A medical history serves to record the patient's complaints and translate them
      into clear-cut, medically defined symptoms. A poorly defined symptom loses most
      of its discriminative power as a diagnostic test for a medical work-up. If
      physicians are uncertain about the exact meaning of a symptom, they have to
      account for the possibility of multiple competing interpretations for the
      identical set of complaints. Multiple possible interpretations of a single
      symptom diminish its value as a diagnostic test and result in test degeneracy. A
      modified Bayes' formula is used to quantify the influence of test degeneracy on
      post-test probability. The physician needs to help his patients to phrase their
      complaints in a fashion that limits the number of possible interpretations. A
      poor medical history diminishes the opportunity to establish a diagnostic
      suspicion with a high probability early on. The subsequent medical work-up has to
      rely on many more tests to confirm the presence of a diagnosis. The poor medical
      history exposes the patient, therefore, to more test-related risks, and prolongs
      the diagnostic process. All these downsides of a poor history ultimately increase
      medical resource utilization and healthcare expenditures.

PMID- 11953700
TI  - Hodgkin's disease presenting as cholestatic hepatitis with prominent ductal
      injury.
AB  - In advanced stages of Hodgkin's disease, liver involvement is common. However,
      Hodgkin's disease mimicking cholestatic hepatitis at presentation is rare. We
      describe a patient with Hodgkin's disease who was initially considered to have
      acute cholestatic hepatitis. Liver biopsy demonstrated prominent bile duct injury
      associated with a florid inflammatory reaction. These changes may represent an
      early stage of ductal injury, subsequently leading to vanishing bile duct
      syndrome, a recently documented mechanism of cholestasis in Hodgkin's disease.

PMID- 11953701
TI  - Focal nodular hyperplasia occurring after blunt abdominal trauma.
AB  - Focal nodular hyperplasia of the liver is a benign neoplasm. The pathogenesis is
      unknown, but it was hypothesized that focal nodular hyperplasia may be a response
      to a vascular abnormality. We report on a case of focal nodular hyperplasia that
      developed in a young patient 1 year after a blunt hepatic injury.

PMID- 11953702
TI  - Management of ischaemic stricture at a gastro-jejunostomy by self-expanding
      metallic stent insertion.
AB  - This report details the use of a self-expanding metallic stent (SEMS) in the
      relief of an ischaemic stricture at a gastro-jejunostomy in a patient who was
      unfit for surgical intervention. Good initial results are reported, along with
      satisfactory long-term follow-up. A brief discussion of the current relevant
      literature is also included.

PMID- 11953703
TI  - Twenty-two years' survival of metastatic gastrinoma evidenced recently by
      somatostatin-receptor-specific scintigraphy.
AB  - An 18-year-old male presented in 1979 with a gastrinoma of unknown primary
      origin. Massive upper-digestive haemorrhage led to total gastrectomy, at which
      histology evidenced liver metastases, confirmed 9 months later at reoperation for
      an intestinal occlusion. Postoperative morphological evidence of liver metastases
      was repeatedly negative using abdominal ultrasound and computerized tomography
      (CT) scans and magnetic resonance imaging (MRI), but a recent somatostatin
      receptor-specific scintigraphy (Octreoscan) was positive only in the liver area.
      Twenty-two years after diagnosis, the primary tumour has not been identified, the
      patient leads a normal life, and his circulating gastrin levels, although still
      elevated at 317-550 pg/ml (normal < 127 pg/ml), have fallen over recent years
      from > 1000 pg/ml. We discuss the relevance of the described prognostic factors.

PMID- 11953706
TI  - Leading the Way.

PMID- 11953705
TI  - It Came to Pass.

PMID- 11953707
TI  - Research Review.

PMID- 11953708
TI  - Legislation.

PMID- 11953709
TI  - Parents' reasons for enrolment of their motor-disabled child in a Dutch
      therapeutic toddler class.
AB  - This article describes and categorizes the reasons why parents enrol their motor
      disabled children in the therapeutic toddler class, a special centre-based
      service in early intervention. The results among a representative Dutch sample of
      84 mothers showed that child-related reasons were considered more important than
      family- and parent-related reasons. Family- and parent-related reasons were
      influenced by the presence and severity of the child's behaviour problems. The
      results of this study are discussed within the context of parental expectations
      in early intervention, and the concept of family centredness.

PMID- 11953710
TI  - Pleasure or utility? Different conditions for boys and girls with disabilities in
      information and communication technology.
AB  - This study focuses on differences between the ways in which we look at girls' and
      boys' computer activities. It is evident that the gender varieties per se
      generate different conditions for boys and girls. Generally, children with
      disabilities have great difficulty defining their needs and wishes. Pedagogues,
      habilitation staff and parents are needed as support for both boys' and girls'
      development. If technology is to be part of this development, we must pay
      attention to it. Research within this area highlights the differences and
      patterns that occur. The study stresses the expectations and experiences that
      parents of children with disabilities have of computer-based activities for their
      children, with a focus on gender-related issues.

PMID- 11953711
TI  - Coping with the consequences of a stroke.
AB  - BACKGROUND AND PURPOSE: Having a stroke constitutes a major life event which
      engenders some types of adaptation in order to try to resume to a "normal" life.
      The objectives of this study were (1) to explore the type of coping strategies
      used following a stroke; (2) to verify if coping strategies change over time, and
      (3) to verify if the coping strategies used are related to age, gender,
      actualization of potential, handicap level and depression. METHODS: A convenience
      sample of 76 participants who had had a stroke was recruited upon discharge from
      a functional intensive rehabilitation unit. Data were collected 2 weeks later and
      6 months later in their own home. Coping strategies were measured using a
      modified version of the Ways of Coping Questionnaire. Actualization of potential
      was measured using the Measure of the Actualization of Potential and handicap
      level was quantified with the LIFE-H. Finally, the Beck Depression Inventory was
      used to evaluate the presence of depressive symptoms. CONCLUSION: The results
      suggest that long after the end of an intensive rehabilitation programme, some
      coping strategies might be more effective in dealing with the consequences of a
      stroke whereas others might be related to some form of inadaptation. However, the
      results should be treated with caution. More research on coping following a
      stroke using mixed methodologies is needed.

PMID- 11953712
TI  - Family needs and burdens of mentally ill offenders.
AB  - A growing number of research projects have been devoted to the study of needs,
      burdens and intervention programmes of families of psychiatric patients due to
      the emphasis on deinstitutionalization and community integration. Although it is
      noted that burdens for families when looking after a patient with a criminal
      history are even heavier and more complicated, studies on identifying family
      needs and burdens for mentally ill offenders have been very limited. This paper
      reviews literature on family burdens and studies on family needs for psychiatric
      patients with a forensic history. Methodological problems of available studies
      are discussed. In addition, a theoretical model that can be used as a conceptual
      guide for the study of burdens of families of mentally ill offenders is
      postulated. Directions for further research are discussed.

PMID- 11953714
TI  - Social and professional reintegration of the long-term unemployed disabled.
      Intervention on the body through adapted physical activities, conative teaching
      skills and social re-energization.

PMID- 11953713
TI  - Taking a new course in research on the effectiveness of interventions. A study of
      physiotherapy interventions for people with musculoskeletal complaints.
AB  - Physiotherapy is a commonly employed intervention for people with musculoskeletal
      complaints. However, due to (methodological) limitations in previous research,
      the effectiveness of physiotherapy interventions has not yet been proven. The aim
      of the present study is twofold. First we try to solve some of the methodological
      problems, of which the most important are selection and endogeneity biases and
      state dependence. Secondly, the effect of a physiotherapy intervention on
      recovery from musculoskeletal complaints is investigated. The probability of
      receiving a physiotherapy intervention is estimated, as well as the probability
      of recovery as a result of this intervention. A longitudinal design is used.
      Analyses are performed using secondary data on a populational level. The
      analytical framework is provided by a Markov model. We use a logit model to
      estimate transition probabilities of this Markov model. Results show that
      experience with physiotherapy in the past is an important predictor for receiving
      physiotherapy in the future. Other predictors of the chance of receiving an
      intervention are also identified. Furthermore, results indicate that the effect
      of a physiotherapy intervention on recovery is negative. It is concluded that
      both the latter effect and the effect of intervention experience can partly be
      explained by medicalization, in spite of a presence of "severe" cases in the
      intervention group.

PMID- 11953715
TI  - Effects of an intensive-period inpatient rehabilitation programme on the
      perceived physical self in moderate chronic obstructive pulmonary disease
      patients.

PMID- 11953716
TI  - Pulmonary function in hemiplegia.

PMID- 11953717
TI  - Electrical stimulation of quadriceps during rehabilitation following proximal
      femoral fracture.

PMID- 11953719
TI  - Energy cost of manual wheelchair propulsion at different speeds.

PMID- 11953718
TI  - Quantitative gait analysis in unconstrained total knee arthroplasty patients.

PMID- 11953720
TI  - WWAMI: a regional approach to pediatric education.

PMID- 11953721
TI  - Emergence of new pathogens in CF: the devil we know or the devil we don't know?

PMID- 11953722
TI  - Outcome in term infants treated with inhaled nitric oxide.

PMID- 11953723
TI  - Thyroid function in the very low birth weight newborn: rescreen or reevaluate?

PMID- 11953724
TI  - Nucleic acid amplification assays for microbial diagnosis: challenges and
      opportunities.

PMID- 11953725
TI  - Clinical research and training: an overview.

PMID- 11953726
TI  - Antibiotic prophylaxis in infants and young children with cystic fibrosis: a
      randomized controlled trial.
AB  - OBJECTIVES: To evaluate whether antistaphylococcal prophylaxis in infants and
      young children with cystic fibrosis (CF) would suppress the acquisition of
      Staphylococcus aureus and delay the onset of the manifestations of
      bronchopulmonary disease. STUDY DESIGN: A 7-year, multicenter, double-blind,
      placebo-controlled study of continuous antistaphylococcal therapy. Otherwise
      healthy children <2 years of age with CF were randomly assigned to be treated
      with daily cephalexin (80-100 mg/kg/day) or placebo. Clinical, microbiologic,
      laboratory, radiographic, and anthropometric outcomes were evaluated. RESULTS: Of
      209 children enrolled, 119 completed a 5- to 7-year course of therapy. Mean age
      at enrollment was 15.6 and 14.1 months in the cephalexin and placebo groups,
      respectively. Respiratory cultures from children treated with cephalexin were
      significantly less likely to be positive for S aureus (6.0% vs 30.4%; P <.001).
      They were, however, much more likely to be positive for Pseudomonas aeruginosa
      (25.6% vs 13.5%; P <.009). These differences became apparent in the first year
      after enrollment and persisted over the duration of the study. In contrast to
      these microbiologic differences, there were no differences in clinical outcome
      measures, including radiographic (Brasfield score, 23.4 vs 23.2) or
      anthropometric scores or pulmonary function. CONCLUSIONS: Although long-term
      prophylaxis with cephalexin successfully delayed the acquisition of S aureus, it
      enhanced colonization with P aeruginosa and did not lead to clinically
      significant improvement in major health outcomes. These data do not support
      routine antistaphylococcal prophylaxisin otherwise healthy infants and young
      children with CF.

PMID- 11953727
TI  - Neurodevelopmental and medical outcomes of persistent pulmonary hypertension in
      term newborns treated with nitric oxide.
AB  - OBJECTIVE: To determine the medical and neurodevelopmental outcome of children
      with moderately severe persistent pulmonary hypertension of the newborn (PPHN)
      treated with or without inhaled nitric oxide (I-NO). STUDY DESIGN: Term infants
      with PPHN and a baseline oxygenation index of 24 +/- 9 at study entry were
      randomly assigned to early treatment with placebo or initial doses of I-NO (5,
      20, and 80 ppm). Outcome was measured at approximately 1 year by frequency of
      hospitalization, growth, and neurodevelopmental and audiologic evaluation.
      RESULTS: Of 155 children enrolled, 144 survived, and there was follow-up for 133.
      No significant differences between the placebo and the I-NO groups were seen in
      any long-term outcome. Rehospitalization occurred in 22%, and growth did not
      differ. The composite neurodevelopment and audiologic outcome showed impairment
      in 46% of the infants. There were major neurologic abnormalities in 13%,
      cognitive delays in 30%, and hearing loss in 19% of the infants. CONCLUSIONS:
      Moderately severe PPHN at 24 hours after birth is associated with high rates of
      rehospitalization and disability at 1 year. Adverse outcomes were the same in I
      NO and control groups.

PMID- 11953728
TI  - Very low birth weight newborns do not need repeat screening for congenital
      hypothyroidism.
AB  - OBJECTIVE: To determine whether repeat screening for congenital hypothyroidism is
      necessary in newborns weighing <1500 g (very low birth weight [VLBW]). STUDY
      DESIGN: All VLBW infants born in the province of Quebec between October 15, 1993,
      and October 15, 1994, had a second filter paper sample requested at 6 weeks of
      age to measure thyrotropin and thyroxine, in addition to these measurements for
      the routine screening sample. We then conducted a survey of all 4 academic
      pediatric endocrinology clinics in the province, inquiring about cases of
      permanent primary congenital hypothyroidism (PPCH) in children born weighing
      <1500 g or who may have been missed by neonatal screening. RESULTS: Two specimens
      were obtained in 465 VLBW newborns. One case of mild transient
      hyperthyrotropinemia was identified. The survey identified 4 VLBW newborns with
      PPCH: 1 girl and 1 boy with dyshormonogenesis, 1 athyreotic girl, and 1 girl with
      thyroid ectopy. All 4 were detected by their initial filter paper specimens. The
      survey also identified 1 case of PPCH in a girl who had a normal neonatal screen
      and normal birth weight. CONCLUSIONS: VLBW newborns with PPCH can mount an
      appropriate thyrotropin response and do not need repeat screening for congenital
      hypothyroidism.

PMID- 11953729
TI  - Indwelling catheters used from the onset of diabetes decrease injection pain and
      pre-injection anxiety.
AB  - OBJECTIVES: To investigate the use of indwelling catheters as injection aids at
      diabetes onset to reduce injection pain and pre-injection anxiety. STUDY DESIGN:
      Forty-one patients aged 8.1 +/- 3.7 years (range, 1-15) participated in this
      open, controlled randomized study. A 10-cm VAS with faces was used for scoring. A
      local anesthetic cream was used before all insertions. The control group used
      insulin pens with standard needles. After one week, the indwelling catheter group
      could choose regular injections but were included in the "intention to treat"
      analysis. RESULTS: Injection pain and anxiety decreased from day 1 to 15 in both
      groups (average, 4.1 injections/day). Pain was significantly lower for indwelling
      catheter injections when scored by parents (median, 1.2 cm vs 2.7 cm; P =.002),
      children/teenagers (0.8 cm vs 1.5 cm; P =.006), and nurses (1.4 cm vs 3.0 cm; P
      =.002). Parental pre-injection anxiety was also lower (1.2 cm vs 2.9 cm; P
      =.016). Taking injections, including inserting catheters, was found to be less
      problematic with an indwelling catheter (1.6 cm vs 3.3 cm;P =.009). During the 6
      month follow-up, injection pain and injection problems were significantly lower
      in the catheter group. Mean catheter indwelling time was 3.7 days. Median pain
      for catheter insertion was 2.1 cm and for glucose testing was 0.9 cm. Sixteen of
      20 patients continued to use indwelling catheters after 2 weeks, and 9 of 20
      after 6 months. CONCLUSIONS: We found an evident relief of pre-injection anxiety
      and injection pain when using indwelling catheters for introducing insulin
      injections at the onset of diabetes.

PMID- 11953730
TI  - Inborn errors of metabolism in the Italian pediatric population: a national
      retrospective survey.
AB  - OBJECTIVE: To estimate at the national level the overall and disease-specific
      incidence of inborn errors of metabolism not mass screened at birth. STUDY
      DESIGN: Prospective nonconcurrent study (1985-1997) on patients 0 to 17 years of
      age, diagnosed in 23 Italian pediatric reference centers. RESULTS: Cases (n =
      1935) were recruited representing an incidence of 1:3707 live births for
      approximately 200 diseases. In the last 5 years the incidence was 1:2758,
      reflecting improved diagnostic facilities, better coverage, increased medical
      awareness, and newly discovered diseases. In this period, the most frequent
      classes of diseases were lysosomal storage disease, 1:8275; disorders of
      carbohydrate metabolism, 1:19,532; organic acidopathies, 1:21,422; and primary
      lactic acidemias, 1:27,106. The most frequent individual diseases were Gaucher
      type I, 1:40,247; glycogenosis type 1a, 1:57,746; methylmalonic acidurias,
      1:61,775; and ornithine transcarbamylase deficiency, 1:69,904. The incidence of
      diseases potentially identifiable with the use of a new neonatal mass screening
      technique is 1:6200. Of surviving patients, 11% reached adulthood by the end of
      the study. CONCLUSIONS: Inborn errors of metabolism constitute a highly
      heterogeneous category of rare diseases, representing a relevant cause of
      morbidity and mortality in childhood. This study quantifies the minimum size of
      the disease burden, providing useful tools for public health and health policy
      planning.

PMID- 11953732
TI  - Effects of manipulating sedentary behavior on physical activity and food intake.
AB  - OBJECTIVES: Sedentary behaviors have been correlated with obesity. We
      investigated whether changes in sedentary behaviors relate to changes in energy
      intake and/or physical activity. STUDY DESIGN: Experimental within-subject
      crossover design in which children participated in three 3-week phases: baseline
      and increased and decreased targeted sedentary behaviors. PARTICIPANTS: Thirteen
      8- to 12-year-old, nonobese children. MEASUREMENTS: Sedentary behaviors were
      measured through the use of daily activity logs, physical activity measured with
      accelerometers, and energy intake measured by means of repeated 24-hour recalls
      collected during each phase. Energy intake, energy expenditure, and energy
      balance per day were calculated. RESULTS: Children showed significant (P <.001)
      increases of 50% and decreases of 53% in targeted sedentary behaviors from
      baseline during the increase and decrease phases, respectively. There was a
      significant (P =.05) increase in energy balance per day (+350.7 kcal) when
      sedentary behaviors were increased, as the result of an increase in energy intake
      per day (+250.9 kcal) and a decrease in energy expenditure (-99.8 kcal). No
      significant changes in energy balance were observed when sedentary behaviors were
      decreased. CONCLUSIONS: Increasing sedentary behaviors had a greater influence on
      physical activity and energy intake than reducing sedentary behavior in nonobese
      youth. In some children, changes in sedentary behaviors may be important to
      modify energy balance and prevent obesity.

PMID- 11953731
TI  - Effects of diet on the neurologic development of children at 5 years of age: the
      STRIP project.
AB  - OBJECTIVES: To evaluate the effects of diet, serum cholesterol concentrations,
      and apolipoprotein E phenotype on neurodevelopment of 5-year-old children. STUDY
      DESIGN: Prospective, 4.4-year cohort study in 496 children. Fat-modified diet was
      introduced to intervention families of 7-month-old infants. Control children
      consumed an unrestricted diet. Nutrient intakes, serum cholesterol, and
      neurodevelopment were studied. The groups were combined in univariate and
      stepwise multivariate logistic regression analyses. RESULTS: In 13-month-old boys
      (girls), energy intake was 996 (938) kcal, fat intake 26.6 (26.4) percent of
      energy (E%), and protein intake 17.2 (17.4) E%. In 5-year-old boys (girls), the
      intakes were 1484 (1364) kcal, 32.1 (31.9) E%, and 15.5 (15.9) E%, respectively.
      The intakes of total fat and saturated fat and serum cholesterol were not
      associated with neurodevelopment. In boys, high intake of protein at 5 years,
      high intakes of protein at 4 years and cholesterol at 2 years, and high intake of
      polyunsaturated fatty acids at 3 years predicted favorable outcomes in the tests
      of speech and language skills, gross motor function and perception, and visual
      motor skills, respectively. Apolipoprotein E phenotype did not influence the test
      performance. CONCLUSIONS: Moderate restriction of dietary fat has no unfavorable
      effects on neurodevelopment in early childhood. However, the quality of fat and
      the relative intake of protein may influence neurodevelopment of the boys.

PMID- 11953733
TI  - Food portions are positively related to energy intake and body weight in early
      childhood.
AB  - OBJECTIVE: To identify portion sizes (quantity ingested at a meal/snack) of foods
      commonly consumed in early childhood, temporal stability, and relations to energy
      intake, weight status, and sociodemographic characteristics. STUDY DESIGN: Three
      samples were evaluated: the Continuing Survey of Food Intakes by Individuals,
      1994 to 1996, 1998 (CSFII 94-96, 98) (n = 1039), the Nationwide Food Consumption
      Survey, 1977 to 1978 (NFCS 77-78) (n = 1045), and a longitudinal sample (n = 55)
      studied from 12 to 18 months. The CSFII 94-96, 98, and NFCS 77-78 samples were
      compared to evaluate secular trends. Change from 12 to 18 months was assessed in
      the longitudinal sample. Relations of portion size to other relevant variables
      were evaluated in the CSFII 94-96, 98 sample. RESULTS: In recent decades,
      portions remained remarkably similar for most foods. An exception was for meat
      portions, which were smaller in recent samples. Portions were longitudinally
      stable for most foods but increased for milk, bread, cereal, juice, and peanut
      butter. Body weight was positively related to energy intake and portion size but
      not number of eating occasions and/or foods. Sociodemographically, portion size
      was inversely related to number of eating occasions and/or foods. CONCLUSIONS:
      Children regulate energy intake largely through portion size. Sociodemographic
      patterns may have implications for later weight status.

PMID- 11953734
TI  - Risk of recurrent stroke in children with sickle cell disease receiving blood
      transfusion therapy for at least five years after initial stroke.
AB  - OBJECTIVE: To test the hypothesis that children with sickle cell disease (SCD)
      who have an initial stroke temporally unrelated to another medical event are at
      higher risk for recurrent stroke than are children who had strokes temporally
      related to medical events. METHODS: A retrospective cohort study of children with
      SCD and stroke who received regularly scheduled blood transfusions for a minimum
      of 5 years was conducted. Medical records were examined for the documentation of
      antecedent or concurrent medical events (hypertension, acute chest syndrome,
      aplastic crisis, fever associated with infection, exchange transfusion)
      associated with physician contact within 14 days before the initial stroke.
      RESULTS: A total of 137 pediatric patients from 14 centers were studied. Mean age
      at first stroke was 6.3 years (1.4 to 14.0 years) with mean follow-up of 10.1
      years (5 to 24 years). Thirty-one (22%) patients had a second stroke (2.2 per 100
      patient years); 26 patients had an identified medical or concurrent event
      associated with their initial stroke. None of these patients had recurrent stroke
      2 or more years after the initial event. The remaining 111 patients had an
      ongoing risk of recurrent stroke (1.9 per 100 patient-years) despite long-term
      transfusions (P =.038). CONCLUSIONS: The absence of an antecedent or concurrent
      medical event associated with an initial stroke is a major risk factor for
      subsequent stroke while receiving regular transfusions.

PMID- 11953735
TI  - Nijmegen breakage syndrome: clinical characteristics and mutation analysis in
      eight unrelated Russian families.
AB  - OBJECTIVE: The purpose of the study was to ascertain patients with Nijmegen
      breakage syndrome (NBS) in the Russian population and characterize the clinical
      phenotype and molecular genotype of these patients. STUDY DESIGN: Eight unrelated
      Russian patients with possible diagnoses of NBS were identified. Family histories
      were collected and clinical and laboratory analyses were carried out. Mutation
      screening of the NBS1 gene was carried out to confirm the diagnosis in 7 cases.
      RESULTS: All patients had the key diagnostic features of NBS. One patient had
      acute myeloblastic leukemia (AML). Two patients had bone marrow aplasia, not
      previously described as a feature of NBS. Mutation screening of the NBS1 gene
      revealed that 6 patients were homozygous for the 657del5 mutation, whereas a
      seventh patient was a compound heterozygote, having the 657del5 mutation and an
      additional novel mutation, 681delT. CONCLUSIONS: Molecular analyses confirmed the
      diagnosis of NBS in 7 of the patients. The surprising finding of bone marrow
      aplasia or AML in 3 of 7 patients raises the possibility of a connection between
      NBS and another DNA damage disorder, Fanconi anemia.

PMID- 11953736
TI  - Transient hyperthyroidism in an adolescent with hydatidiform mole.

PMID- 11953737
TI  - Identification of Pneumocystis carinii DNA by polymerase chain reaction in
      necropsy lung samples from children dying of respiratory tract illnesses.
AB  - Polymerase chain reaction for Pneumocystis carinii DNA was performed on necropsy
      lung samples from children by means of P carinii -specific primers.P carinii DNA
      was identified in 22 of 22 (100%) samples with histologically proven P carinii
      pneumonia and 13 of 75 (17%) with non-P carinii pneumonia respiratory illness
      (sensitivity, 100%; specificity, 83%). The low specificity precludes the use of
      polymerase chain reaction as an alternative to histopathologic diagnosis.

PMID- 11953738
TI  - Efficacy of latex avoidance for primary prevention of latex sensitization in
      children with spina bifida.
AB  - Over 6 years, the prevalence of latex sensitization fell from 4/15 (26.7%) to
      1/22 (4.5%) in children with spina bifida treated in a latex-free environment
      from birth compared with historic controls. These precautions appear to be
      efficacious for the primary prevention of latex sensitization.

PMID- 11953739
TI  - Dopamine effects on pulmonary artery pressure in hypotensive preterm infants with
      patent ductus arteriosus.
AB  - We investigated the effects of dopamine on pulmonary artery pressure in 18
      ventilated hypotensive preterm neonates by using the flow characteristics of the
      ductal shunt. Dopamine has variable effects on pulmonary/systemic mean arterial
      pressure ratio with half the neonates showing an increase in pulmonary pressure
      relative to systemic pressure.

PMID- 11953740
TI  - PR-segment changes in childhood pericarditis.

PMID- 11953741
TI  - Celiac disease case finding in children in primary care.

PMID- 11953742
TI  - Jaw-thrust and continuous positive airway pressure in infants.

PMID- 11953743
TI  - Conscious sedation.

PMID- 11953744
TI  - Measles prevention-- just vaccinate.

PMID- 11953745
TI  - Segregation at three loci explains familial and population risk in Hirschsprung
      disease.
AB  - Hirschsprung disease (HSCR), the most common hereditary cause of intestinal
      obstruction, shows considerable variation and complex inheritance. Coding
      sequence mutations in RET, GDNF, EDNRB, EDN3 and SOX10 lead to long-segment (L
      HSCR) and syndromic HSCR but fail to explain the transmission of the much more
      common short-segment form (S-HSCR). We conducted a genome scan in families with S
      HSCR and identified susceptibility loci at 3p21, 10q11 and 19q12 that seem to be
      necessary and sufficient to explain recurrence risk and population incidence. The
      gene at 10q11 is probably RET, supporting its crucial role in all forms of HSCR;
      however, coding sequence mutations are present in only 40% of linked families,
      suggesting the importance of noncoding variation. Here we show oligogenic
      inheritance of S-HSCR, the 3p21 and 19q12 loci as RET-dependent modifiers, and a
      parent-of-origin effect at RET. This study demonstrates by a complete genetic
      dissection why the inheritance pattern of S-HSCR is nonmendelian.

PMID- 11953746
TI  - Genetic evidence that oxidative derivatives of retinoic acid are not involved in
      retinoid signaling during mouse development.
AB  - Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal
      signaling molecule that acts in developing and adult tissues. The Cyp26a1
      (cytochrome p450, 26) protein metabolizes retinoic acid into more polar
      hydroxylated and oxidized derivatives. Whether some of these derivatives are
      biologically active metabolites has been debated. Cyp26a1(-/-) mouse fetuses have
      lethal morphogenetic phenotypes mimicking those generated by excess retinoic acid
      administration, indicating that human CYP26A1 may be essential in controlling
      retinoic acid levels during development. This hypothesis suggests that the
      Cyp26a1(-/-) phenotype could be rescued under conditions in which embryonic
      retinoic acid levels are decreased. We show that Cyp26a1(-/-) mice are
      phenotypically rescued by heterozygous disruption of Aldh1a2 (also known as
      Raldh2), which encodes a retinaldehyde dehydrogenase responsible for the
      synthesis of retinoic acid during early embryonic development. Aldh1a2
      haploinsufficiency prevents the appearance of spina bifida and rescues the
      development of posterior structures (sacral/caudal vertebrae, hindgut, urogenital
      tract), while partly preventing cervical vertebral transformations and hindbrain
      pattern alterations in Cyp26a1(-/-) mice. Thus, some of these double-mutant mice
      can reach adulthood. This study is the first report of a mutation acting as a
      dominant suppressor of a lethal morphogenetic mutation in mammals. We provide
      genetic evidence that ALDH1A2 and CYP26A1 activities concurrently establish local
      embryonic retinoic acid levels that must be finely tuned to allow posterior organ
      development and to prevent spina bifida.

PMID- 11953747
TI  - Retinoid metabolism: a balancing act.

PMID- 11953748
TI  - Dissecting Hirschsprung disease.

PMID- 11953749
TI  - A neuronal receptor, neuropilin-1, is essential for the initiation of the primary
      immune response.
AB  - The initiation of a primary immune response requires contact between dendritic
      cells (DCs) and resting T cells. However, little is known about the proteins that
      mediate this initial contact. We show here that neuropilin-1, a receptor involved
      in axon guidance, was expressed by human DCs and resting T cells both in vitro
      and in vivo. The initial contact between DCs and resting T cells led to
      neuropilin-1 polarization on T cells. DCs and resting T cells specifically bound
      soluble neuropilin-1, and resting T cells formed clusters with neuropilin-1
      transfected COS-7 cells in a neuropilin-1-dependent manner. Functionally,
      preincubation of DCs or resting T cells with blocking neuropilin-1 antibodies
      inhibited DC-induced proliferation of resting T cells. These data suggest that
      neuropilin-1 mediates interactions between DCs and T cells that are essential for
      initiation of the primary immune response and show parallels between the nervous
      and immune systems.

PMID- 11953750
TI  - Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell
      death pathways.
AB  - Here we report that synaptic and extrasynaptic NMDA (N-methyl-D-aspartate)
      receptors have opposite effects on CREB (cAMP response element binding protein)
      function, gene regulation and neuron survival. Calcium entry through synaptic
      NMDA receptors induced CREB activity and brain-derived neurotrophic factor (BDNF)
      gene expression as strongly as did stimulation of L-type calcium channels. In
      contrast, calcium entry through extrasynaptic NMDA receptors, triggered by bath
      glutamate exposure or hypoxic/ischemic conditions, activated a general and
      dominant CREB shut-off pathway that blocked induction of BDNF expression.
      Synaptic NMDA receptors have anti-apoptotic activity, whereas stimulation of
      extrasynaptic NMDA receptors caused loss of mitochondrial membrane potential (an
      early marker for glutamate-induced neuronal damage) and cell death. Specific
      blockade of extrasynaptic NMDA receptors may effectively prevent neuron loss
      following stroke and other neuropathological conditions associated with glutamate
      toxicity.

PMID- 11953751
TI  - Clock mutation lengthens the circadian period without damping rhythms in
      individual SCN neurons.
AB  - Spontaneous discharges of individual neurons in the suprachiasmatic nucleus (SCN)
      of Clock mutant mice were recorded for over 5 days in organotypic slice cultures
      and dispersed cell cultures using a multi-electrode dish. Circadian rhythms with
      periods of about 27 hours were detected in 77% of slice cultures and 15% of
      dispersed cell cultures derived from Clock/Clock homozygotes. These findings
      indicate that the Clock mutation lengthens the circadian period but does not
      abolish the circadian oscillation, and suggest an important role of intercellular
      communication in the expression of circadian rhythm in the SCN.

PMID- 11953752
TI  - Neural stem cells from adult hippocampus develop essential properties of
      functional CNS neurons.
AB  - Neural stem cells are present both in the developing nervous system and in the
      adult nervous system of all mammals, including humans. Little is known, however,
      about the extent to which stem cells in adults can give rise to new neurons. We
      used immunocytochemistry, electron microscopy, fluorescence microscopy (FM
      imaging) and electrophysiology to demonstrate that progeny of adult rat neural
      stem cells, when co-cultured with primary neurons and astrocytes from neonatal
      hippocampus, develop into electrically active neurons and integrate into neuronal
      networks with functional synaptic transmission. We also found that functional
      neurogenesis from adult stem cells is possible in co-culture with astrocytes from
      neonatal and adult hippocampus. These studies show that neural stem cells derived
      from adult tissues, like those derived from embryonic tissues, retain the
      potential to differentiate into functional neurons with essential properties of
      mature CNS neurons.

PMID- 11953753
TI  - Ca(2+)-independent but voltage-dependent secretion in mammalian dorsal root
      ganglion neurons.
AB  - We have investigated the Ca(2+) dependence of vesicular secretion from the soma
      of dorsal root ganglion (DRG) neurons, which secrete neuropeptides by exocytosis
      of dense-core vesicles. In patch-clamped somata of rat DRG neurons, we found a
      depolarization-induced membrane capacitance increase (DeltaC(m)) in the absence
      of extracellular Ca(2+) and in the presence of a Ca(2+) chelator (BAPTA) in the
      intracellular solution. Depletion of internal Ca(2+) stores by thapsigargin in
      the Ca(2+)-free bath also did not block the DeltaC(m), indicating that Ca(2+)
      release from internal Ca(2+) stores may not have been involved. Furthermore, the
      Ca(2+)-independent DeltaC(m) was blocked by whole-cell dialysis with tetanus
      toxin and was accompanied by pulsatile secretion of false transmitters, as
      detected by amperometric measurements. These results indicate the existence of
      Ca(2+)-independent but voltage-dependent vesicular secretion (CIVDS) in a
      mammalian sensory neuron.

PMID- 11953754
TI  - Active maintenance in prefrontal area 46 creates distractor-resistant memory.
AB  - How does the brain maintain information in working memory while challenged by
      incoming distractions? Using functional magnetic resonance imaging (fMRI), we
      measured human brain activity during the memory delay of a spatial working memory
      task with distraction. We found that, in the prefrontal cortex (PFC), the
      magnitude of activity sustained throughout the memory delay was significantly
      higher on correct trials than it was on error trials. By contrast, the magnitude
      of sustained activity in posterior areas did not differ between correct and error
      trials. The correlation of activity between posterior areas was, however,
      associated with correct memory performance after distraction. On the basis of
      these findings, we propose that memory representations gain resistance against
      distraction during a period of active maintenance within working memory. This may
      be mediated by interactions between prefrontal and posterior areas.

PMID- 11953755
TI  - Structural characterization of a subtype-selective ligand reveals a novel mode of
      estrogen receptor antagonism.
AB  - The R,R enantiomer of 5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol
      (THC) exerts opposite effects on the transcriptional activity of the two estrogen
      receptor (ER) subtypes, ER alpha and ER beta. THC acts as an ER alpha agonist and
      as an ER beta antagonist. We have determined the crystal structures of the ER
      alpha ligand binding domain (LBD) bound to both THC and a fragment of the
      transcriptional coactivator GRIP1, and the ER beta LBD bound to THC. THC
      stabilizes a conformation of the ER alpha LBD that permits coactivator
      association and a conformation of the ER beta LBD that prevents coactivator
      association. A comparison of the two structures, taken together with functional
      data, reveals that THC does not act on ER beta through the same mechanisms used
      by other known ER antagonists. Instead, THC antagonizes ER beta through a novel
      mechanism we term 'passive antagonism'.

PMID- 11953756
TI  - Structure of the 16S rRNA pseudouridine synthase RsuA bound to uracil and UMP.
AB  - In Escherichia coli, the pseudouridine synthase RsuA catalyzes formation of
      pseudouridine (psi) at position 516 in 16S rRNA during assembly of the 30S
      ribosomal subunit. We have determined the crystal structure of RsuA bound to
      uracil at 2.0 A resolution and to uridine 5'-monophosphate (UMP) at 2.65 A
      resolution. RsuA consists of an N-terminal domain connected by an extended linker
      to the central and C-terminal domains. Uracil and UMP bind in a cleft between the
      central and C-terminal domains near the catalytic residue Asp 102. The N-terminal
      domain shows structural similarity to the ribosomal protein S4. Despite only 15%
      amino acid identity, the other two domains are structurally similar to those of
      the tRNA-specific psi-synthase TruA, including the position of the catalytic Asp.
      Our results suggest that all four families of pseudouridine synthases share the
      same fold of their catalytic domain(s) and uracil-binding site.

PMID- 11953757
TI  - Structural basis of translational control by Escherichia coli threonyl tRNA
      synthetase.
AB  - Escherichia coli threonyl-tRNA synthetase (ThrRS) represses the translation of
      its own messenger RNA by binding to an operator located upstream of the
      initiation codon. The crystal structure of the complex between the core of ThrRS
      and the essential domain of the operator shows that the mRNA uses the recognition
      mode of the tRNA anticodon loop to initiate binding. The final positioning of the
      operator, upon which the control mechanism is based, relies on a characteristic
      RNA motif adapted to the enzyme surface. The finding of other thrS operators that
      have this conserved motif leads to a generalization of this regulatory mechanism
      to a subset of Gram-negative bacteria.

PMID- 11953758
TI  - History of diabetes mellitus.
AB  - Clinical features similar to diabetes mellitus were described 3000 years ago by
      the ancient Egyptians. The term "diabetes" was first coined by Araetus of
      Cappodocia (81-133AD). Later, the word mellitus (honey sweet) was added by Thomas
      Willis (Britain) in 1675 after rediscovering the sweetness of urine and blood of
      patients (first noticed by the ancient Indians). It was only in 1776 that Dobson
      (Britain) firstly confirmed the presence of excess sugar in urine and blood as a
      cause of their sweetness. In modern time, the history of diabetes coincided with
      the emergence of experimental medicine. An important milestone in the history of
      diabetes is the establishment of the role of the liver in glycogenesis, and the
      concept that diabetes is due to excess glucose production Claude Bernard (France)
      in 1857. The role of the pancreas in pathogenesis of diabetes was discovered by
      Mering and Minkowski (Austria) 1889. Later, this discovery constituted the basis
      of insulin isolation and clinical use by Banting and Best (Canada) in 1921.
      Trials to prepare an orally administrated hypoglycemic agent ended successfully
      by first marketing of tolbutamide and carbutamide in 1955. This report will also
      discuss the history of dietary management and acute and chronic complications of
      diabetes.

PMID- 11953759
TI  - The current status of Helicobacter pylori.
AB  - We present a review of the current status of Helicobacter pylori infection, and
      focus on the clinical issues facing physicians with regards to its pathogenicity,
      diagnosis and treatment. We have attempted to address the important clinical
      issues relevant to the subject, and summarize the currently accepted concepts
      concerning Helicobacter pylori. Our knowledge regarding Helicobacter pylori
      biology is enormous, but detailed knowledge on its transmission is still far from
      clear. Helicobacter pylori is mainly involved in gastrointestinal and possibly in
      other extra-intestinal disorders. There are differences in the clinical
      presentation in various geographical regions resulting from variations in the
      genetic make-up of Helicobacter pylori. There is still need for more simple, cost
      effective, accurate and less invasive diagnostic techniques. The gold standard
      treatment is the one-week proton pump inhibitor-based triple regimen as first
      line, with quadruple therapy as a 2nd line. Helicobacter pylori resistance to the
      main antimicrobials needs to be defined in particular geographical areas.

PMID- 11953760
TI  - Difficulties faced when conducting primary health care programs in rural areas.
AB  - OBJECTIVE: The aim of this study is to explore the difficulties that face primary
      health care teams who work in rural areas in Aseer region, Kingdom of Saudi
      Arabia. METHODS: This study was carried out in 1999 by distributing a multi
      purposes questionnaire to all members of health teams who work in the primary
      health care centers located in the rural areas of Aseer region, Kingdom of Saudi
      Arabia. This questionnaire consisted of 3 parts that were concerned with the
      characteristics of primary health care centers teams and difficulties faced by
      them while conducting primary health care programs during their daily activities
      at primary health care centers. Data was entered and analyzed by personal
      computer which was provided with statistical package for social sciences.
      RESULTS: A total of 68 primary health care centers were located in the rural
      areas of Aseer region, Kingdom of Saudi Arabia. Those primary health care centers
      serve 127,880 individuals who live in 657 villages. Three hundred and four
      members of the primary health care centers teams answered our questionnaire, 23%
      were physicians, 45% were nurses and 17% were Saudis. Thirty percent reported
      that they face some difficulties during conducting primary health care programs
      and 24% reported difficulties during dealing with clients. Most of the
      difficulties were the lack of medical facilities, rough roads and languages
      barriers. CONCLUSION: This study revealed that approximately one 3rd of primary
      health care teams who work in the rural areas of Aseer region, Kingdom of Saudi
      Arabia face significant difficulties that will affect the introducing of
      essential primary health care programs. A multi-sectoral integrated approach is
      mandatory to overcome these difficulties and introduce good quality care.

PMID- 11953761
TI  - Missed appointments at public hospitals in Riyadh, Saudi Arabia.
AB  - OBJECTIVE: Failure to keep appointments poses many problems for patients,
      physicians and health personnel. The objective of the study is to identify
      factors influencing appointment failure in Riyadh Central Hospital, Riyadh,
      Kingdom of Saudi Arabia. METHODS: The study sample consisted of 500 Saudi
      patients selected randomly from Riyadh Central Hospital's records. Two hundred
      and fifty were selected from patients who broke at least one appointment and
      another 250 were selected from patients who have a history of keeping records.
      Interviews were carried out by telephone using a structured questionnaire, only
      426 patients consented to participate in the study. RESULTS: The study showed
      that appointment failure rate is 30%. The data revealed no associations between
      missed appointment, behavior and age, income, travel time and method of
      transportation. None of the health related variables investigated were associated
      with missed appointments. The breakers stated waiting time before seeing a
      doctor, time from scheduling to appointments, transportation (particularly for
      women) and forgetfulness as the main reasons for missing appointments.
      CONCLUSION: Broken appointments can be reduced by continuous health education for
      patients, improving efficiency of health administrators, telephone reminders and
      by physicians negotiating a follow-up schedule for their patients.

PMID- 11953762
TI  - Prevalence of hepatitis C virus antibodies among intravenous drug abusers and
      prostitutes in Damascus, Syria.
AB  - OBJECTIVE: In studies of risk factors among patients presenting with acute and
      chronic hepatitis C, a history of intravenous drug use is the most common
      finding, accounting for 40% or more of subjects. The prevalence of anti-hepatitis
      C virus antibodies among intravenous drug users is considered one of the highest
      numbers among high risk groups. Whether hepatitis C virus is transmitted
      efficiently or at all via sexual contact remains controversial. Therefore, the
      prevalence of hepatitis C virus antibodies among a group of Syrian intravenous
      drug users, prostitutes, and blood donors was studied. METHODS: The prevalence of
      anti-hepatitis C virus in a population of 38 Syrian intravenous drug abusers, 102
      Syrian prostitutes, and 2100 blood donors, was carried out in the laboratory of
      Al-Assad University Hospital, Damascus, Syria. Antibodies of hepatitis C virus
      were studied by 3rd generation enzyme immunoassay. Hepatitis B surface antigen
      and antibodies to hepatitis B core were carried out using enzyme immunoassays.
      Liver enzymes (alanine aminotransferase, aspartate aminotransferase) and total
      bilirubin were measured using reagents on chemistry autoanalyzer (Hitachi 911).
      Intravenous drug users group (38) was aged 31 5.6 years, 33 males and 5 females.
      Prostitutes group (102) were aged 25.1 7 years. Blood donors group (2100) aged
      were 26.3 10.3 years, 1960 males and 140 females. RESULTS: The prevalence of
      hepatitis C virus antibodies was 60.5% among intravenous drug abusers, 1.96%
      among the prostitutes group, and 0.95% among blood donors group. Whereas, the
      positivity of hepatitis B surface antigen was 5.3% among the intravenous drug
      abusers, 10.8% among the prostitutes group, and 3.8% among blood donors group.
      Biochemical parameter results were compared to the results of these parameters
      that were determined in a group of healthy members (blood donors) during our
      study. CONCLUSION: The prevalence of hepatitis C virus antibodies among
      intravenous drug abusers is considered the highest number among high risk groups,
      however, it is comparable to that reported in other countries. The impact of
      hepatitis C among drug users is profound, amplifying the spread of hepatits C
      virus infection and sustaining it in the general population. The prevalence of
      anti-hepatitis C virus among the prostitutes group was a little higher than that
      determined among the general population. The transmission of hepatitis C virus
      via a sexual route is still common and important. The control of the sexual
      behavior may have a role in minimizing the spread of this pathogen among the
      general population.

PMID- 11953763
TI  - An in-vitro study of the effects of various disinfectants on prosthetic and
      surface materials.
AB  - OBJECTIVE: This study assessed the effect of various disinfectants on several
      contaminated prosthetic and surface-covering materials. METHODS: The efficacy of
      6 disinfectants used at King Abdulaziz University, Jeddah, Kingdom of Saudi
      Arabia, on prosthetic and surface-covering materials, irreversible hydrocolloid
      and elastomer impression materials, wax, acrylic resin, metal, bench-covering
      material, and floor carpet. These materials were contaminated with Pseudomonas
      aeruginosa, Escherichia coli, and Staphylococcus aureus. Counts of viable
      bacteria on the materials was determined by incubated replica plating on blood
      agar plates at 5 minute intervals. A 3 way non parametric analysis of variance
      was used to evaluate the main effects and interactions of the disinfectants,
      bacteria, and materials. RESULTS: Statistical analysis showed that material, type
      of disinfectant, and interactions between material and bacteria were significant.
      Carpet has a significantly higher bacterial count than many other items (P <
      0.0001) such as acrylic resin, irreversible hydrocolloid, chrome-cobalt casting,
      and laminated bench surfaces. CONCLUSION: Quaternary ammonia compound and the
      tertiary ammonia phenol were the most effective disinfectants. Efficacy of the
      disinfectant depends partly on the bacteria used for contamination. Carpets in
      dental clinics showed high potential to retain microorganisms.

PMID- 11953764
TI  - Streptococcus pneumoniae resistance to penicillin and ceftriaxone in a tertiary
      care center in Saudi Arabia.
AB  - OBJECTIVE: The proportion of penicillin and ceftriaxone resistant Streptococcus
      pneumoniae isolates and associated risk factors varies by geographic areas in the
      world. We conducted a retrospective study to determine the extent of penicillin
      and ceftriaxone non-susceptible Streptococcus pneumoniae bacteremia in a tertiary
      care medical center in the city of Riyadh, Kingdom of Saudi Arabia. METHODS: We
      reviewed 172 episodes of Streptrococcus pneumoniae bacteremic diseases involving
      160 hospitalized patients at King Faisal Specialist Hospital and Research Centre,
      Riyadh, Kingdom of Saudi Arabia, over a 5 year period between January 1995
      through to December 1999. Patients' characteristics and underlying illnesses of
      those patients with bacteremias and meningitis caused by Streptococccus
      pneumoniae as well as antimicrobial susceptibility were examined. RESULTS: The
      majority of patients affected with Streptococcus pneumoniae bacteremia were
      children <5 years of age (number=91, 53%). Malignant diseases were the main
      underlying diagnosis in our patient population affected with pneumoncoccal
      bacteremia (number=46, 27%). Overall (51%) of the isolates were penicillin non
      susceptible; of these (7%) were highly resistant. The overall resistance rate to
      ceftriaxone was 7%. CONCLUSION: With the high prevalence in Streptococcus
      pneumoniae antimicrobial resistance to penicillin and ceftriaxone, it is
      important to continue surveillance of infections caused by Streptococcus
      pneumoniae, and also we recommend that guidelines for treatment and prevention of
      pneumococcal infection must be addressed by health care and public health
      agencies.

PMID- 11953765
TI  - Kikuchi[corrected]-Fujimoto [corrected] disease.
AB  - OBJECTIVE: Kukuchi-Fujimito disease is a rare, benign and self limiting
      condition, which usually presents with lymphadenopathy or fever of an unknown
      etiology, or both. Its rarity, as well as the similarity of its clinical features
      to other more common conditions, contribute to overlooking it in the differential
      diagnosis of patients presenting with lymphadenopathy or fever of an unknown
      etiology. METHODS: The study was carried out at Qatif Central Hospital, Qatif,
      Kingdom of Saudi Arabia. All lymph node excisional biopsies received in the
      histopathology laboratory between 1989 and 1999 were evaluated and those
      diagnosed as Kukuchi-Fujimito disease were reviewed for clinical data and
      histological findings. RESULTS: A total of 6 cases were diagnosed as Kukuchi
      Fujimito disease out of 390 lymph node biopsies. All patients were young with an
      average age of 21.5 years and equal sex distribution. Enlarged cervical lymph
      nodes with or without fever were the most familiar presenting symptoms. Anemia
      and leukopenia were observed in 3 patients. There was no recurrence of the
      lymphadenopathy over a period of 1-12 years follow up. CONCLUSION: Kukuchi
      Fujimito disease although rare should be included in the differential diagnosis
      of patients presenting with lymphadenopathy as well as fever of an unknown
      origin. To obviate unnecessary investigations and therapeutic trials, these
      patients should undergo early lymph node biopsy which must be interpreted by an
      experienced pathologist.

PMID- 11953766
TI  - Pattern of clinical features of Kawasaki disease.
AB  - OBJECTIVE: To study the pattern of clinical features, complications, and outcome
      of Kawasaki disease among Saudi children. METHODS: Medical records and referral
      letters of all children (1997 through to 2001) diagnosed with Kawasaki disease
      were reviewed. This study was carried out at King Faisal Specialist Hospital and
      Research Center, Riyadh, Kingdom of Saudi Arabia. Collected data included
      clinical features, laboratory results, echocardiogram findings, therapy,
      complications and outcome. RESULTS: Thirteen children (10 boys, 3 girls) were
      reviewed, age range from 0.3 to 7 years (mean 3.4 years). Nine patients met 5 out
      of 6 criteria for the diagnoses of Kawasaki disease and 4 met 4 out of 6 criteria
      and coronary aneurysm. Thirteen patients had fever and skin rash for more than 5
      days, 12 had extremity and oral mucus changes, 9 had bilateral conjunctivitis,
      and 7 had cervical lymph node enlargement. Other associated clinical features
      include diarrhea, and aseptic meningitis in 3 patients, ischemia of the fingers
      and toes in 2, arthritis in 2, arthralgia in one, seizure and pneumonia in one.
      Hepatosplenomegaly, pancytopenia and elevated liver enzymes in one, hepatomegaly
      and normal liver enzymes in 2 patients. Cardiac complication seen in 4 patients
      (30%), all of them were boys, 3 had coronary artery aneurysm (4-7 mm) and one had
      giant aneurysm (9mm), one of the 3 patients had axillary and subclavian artery
      aneurysm as well. Two out 4 patients were treated with intravenous immunoglobulin
      and aspirin within 10 days of illness and one was treated on day 21 and one was
      treated with aspirin alone. Aneurysmal changes persisted in 3 patients and
      resolved in one patient who was treated early. Extra-cardiac complications
      include reaction to intravenous immunoglobulin, coagulopathy, thrombocytopenia,
      hemophagocytic syndrome and ischemia of peripheral extremities. CONCLUSION: Our
      observation showed a high percentage (30%) of coronary aneurysm and unusual
      complications, this is most likely due to delay in the diagnosis and initiation
      of treatment.

PMID- 11953767
TI  - Urinary iodine excretion and maternal thyroid function. During pregnancy and
      postpartum.
AB  - OBJECTIVE: To evaluate urinary iodine excretion during the course of pregnancy
      and postpartum in relation to maternal and neonatal thyroid function parameters
      in Saudi women living in Jeddah, Kingdom of Saudi Arabia. METHODS: A prospective
      longitudinal study was conducted on Saudi normal pregnant women during the course
      of pregnancy (N=80), at term and 6-10 weeks postpartum (N=65), during the period
      January 1997 through to December 2000. Maternal urinary iodine excretion was
      determined together with serum levels of total thyroxine, total tri
      iodothyronine, free thyroxine, free tri-iodothyronine, thyrotropin, reverse tri
      iodothyronine, thyroxine-binding globulin and thyroglobulin. A group of non
      pregnant woman (N=200) were included for comparative purposes. Data were also
      analyzed for significant trends using ANOVA. Neonatal serum levels of total
      thyroxine, total tri-iodothyronine, free thyroxine, thyrotropin, thyroxine
      binding globulin, and thyroglobulin were also measured. RESULTS: Changes in
      urinary iodine excretion and in serum thyroid function parameters during the
      course of pregnancy, at term and postpartum have been demonstrated. Subclinical
      iodine deficiency was evident in 28.8% of pregnant women at term and 11.5% of
      women at 6-10 weeks postpartum. Serum total thyroxine and total tri-iodothyronine
      levels increased in the first trimester (P<0.001) and remained elevated at term
      (P<0.001). Serum free thyroxine levels showed a significant decrease by the 2nd
      trimester (P<0.001) and continued to decrease in the 3rd trimester (P<0.001).
      Serum free tri-iodothyronine showed continuous decrease throughout gestation.
      Thyrotropin levels were decreased during the first and 2nd trimesters (P<0.001)
      but then increased to be comparable to non-pregnant values. Serum reverse tri
      iodothyronine increased during the first and 2nd trimesters (P<0.001). There was
      a significant increase in serum thyroxine-binding globulin and thyroglobulin
      levels during the course of pregnancy. A significant negative correlation between
      thyrotropin and human chorionic gonadotropin levels was observed throughout
      pregnancy (r=-0.31, P<0.001). The observed correlation was stronger (r=-0.37;
      P<0.001) in the first trimester as compared to that in the second (r=-0.164;
      P<0.001) or the third (r=-0.125; P<0.269) trimester. There was a negative
      correlation between maternal free thyroxine and neonatal thyrotropin (r=-0.70;
      P<0.001). Positive correlation was found between neonatal total thyroxine and
      birth weight (r=0.61; P<0.001) and maternal urinary iodine concentration
      (P<0.001). CONCLUSION: The changes in urinary iodine excretion during the course
      of pregnancy were documented. The decrease in free thyroxine and free tri
      iodothyronine and the increase in reverse tri-iodothyronine concentrations during
      pregnancy resemble the changes in thyroid hormones seen in non-thyroidal illness.
      Moreover, the changes in thyrotropin in relation to that of human chorionic
      gonadotropin support the view that the thyroid gland is not primarily thyrotropin
      driven in early pregnancy. The results suggest that a more complex control may
      finally regulate maternal thyroid activity; the pituitary and the chorionic
      systems both function in an independent way in response to possible different
      feedback stimuli. This could be a physiological adaptation enabling energy
      conservation during the high metabolic demands of pregnancy. Finally, the results
      of the present study point to the need of an increased iodine supply in Saudi
      pregnant women living in Jeddah, Kingdom of Saudi Arabia to decrease the
      potential consequences of low iodine intake on maternal thyroid economy.

PMID- 11953768
TI  - Assisted breech delivery, is the art fading?
AB  - OBJECTIVE: To review the modes of breech delivery over a 5 year period in Khamis
      Civil Hospital, Khamis Mushayt, Kingdom of Saudi Arabia, and to evaluate the
      trend and associated complications. METHODS: Relevant data was extracted from the
      delivery room records of all women delivered in Khamis Civil Hospital, Khamis
      Mushayt, Kingdom of Saudi Arabia, from 1st January 1996 through 31st December
      2000. Available data was analyzed. RESULTS: There were 375 breech deliveries,
      constituting 2.8% of the entire deliveries in the hospital. Eighty-two percent of
      the breeches were delivered by cesarean section while 18% had assisted vaginal
      delivery (p=0.0193). Amongst 72 primigravidae breeches, 68 (94.4%) were delivered
      by cesarean section while 238 (78.5%) out of 303 multigravidae were delivered by
      cesarean section. There were 2 unexplained neonatal deaths among the vaginal
      delivery group in multigravidae. Cesarean delivery was associated with less
      morbidity compared to vaginal delivery. CONCLUSION: This study has demonstrated a
      significant increase in delivery of breeches by cesarean section and the
      resultant drop, in the number available for assisted breech delivery. Less
      obstetricians will therefore be exposed practically to the art of assisted breech
      delivery. Most practicing obstetricians seem to be more inclined towards
      delivering breeches by cesarean section. If this trend continues, the art of
      assisted breech delivery may fade.

PMID- 11953769
TI  - High frequency of satellite association in metaphases of infertile male patients.
AB  - OBJECTIVE: The present study is designed to evaluate the contribution of
      satellite association phenomenon on spermatogenic impairment. METHODS: During a
      one year period, January 1999 through to January 2000, the frequency of satellite
      association has been investigated in 57 patients, with the clinical diagnosis of
      male infertility. This study was carried out at the Middle Euphrates Center for
      Cancer Researches, College of Medicine, Kufa University, Kufa, Iraq. Of those 57
      patients, 33 patients were diagnosed with azoospermia and 24 patients with
      oligospermia, the efficacy evaluation was based on the measurement of 8 satellite
      association parameters. Blood culture and chromosome harvesting was carried out
      according to our standard methods. RESULTS: Our experience of association
      behavior of acrocentric chromosome in the 57 infertile males showed statistically
      significant difference in infertile male classes compared to control groups.
      Eight studied parameters were included in the evaluation (P<0.005). CONCLUSION:
      The significant increase in the satellite association is proposed to have another
      indirect causal factor, which influenced spermatogenesis. Furthermore, the
      satellite association technique may be used as a laboratory method for the
      evaluation of male infertility.

PMID- 11953770
TI  - Causes of infant mortality in Jordan.
AB  - OBJECTIVE: Jordan lacks accurate information on mortality and related indicators.
      Reporting of infant deaths is defective. Infant mortality rate based on
      registered deaths was 6/1000 live births, while estimates of this rate based on
      indirect methods varied between 29-70/1000 live births. Causes of death in
      general are grossly misrepresented in death certificates. The objective of this
      paper is to explore, in-depth, causes of infant mortality and related indicators.
      METHODS: An assessment of causes of death by verbal autopsy was carried out at
      the Department of Family and Community Medicine, University of Jordan, Amman,
      Jordan. This was applied between November 1995 through to October 1996, to a
      random sample of 200,000 persons living in 100 clusters representing the
      population and all geographic areas of Jordan. The verbal autopsy instrument was
      based on algorithms and filter questions to determine the underlying cause of
      death. In this sample there were 6028 infants among them 129 deaths were
      identified. Infant deaths were analyzed according to rates and causes of death
      were classified according to International Classification of Diseases (10th
      revision). RESULTS: Age-specific death rate was 21.4/1000 infants and gender
      specific death rates were 22.6/1000 male infants for males and 20.1/1000 female
      infants for females. The 3 leading causes of infant death were conditions
      originating in the perinatal period, congenital malformations and diseases of the
      respiratory system. The leading cause of death in the neonatal period was
      conditions originating in the perinatal period, while in the post-neonatal
      period, it was congenital malformations. Prematurity was the leading contributory
      cause of infant death. CONCLUSION: This study showed that causes of infant
      mortality in Jordan tend to be similar to those prevailing in developed
      countries.

PMID- 11953771
TI  - Proinflammatory cytokines in open versus laparoscopic cholecystectomy.
AB  - OBJECTIVE: Laparoscopic cholecystectomy, a minimal access surgery, is fast
      replacing open cholecystectomy and is being associated with less trauma. The
      objective of this study was to compare the proinflammatory cytokine levels in
      both laparoscopic cholecystectomy and open cholecystectomy. METHODS: This study
      was carried out at Aseer Central Hospital, Aseer region, Abha Private Hospital
      and the College of Medicine and Medical Sciences, King Khalid University, Abha,
      Kingdom of Saudi Arabia, during the time period October 1998 through to November
      2000. Sixty-one patients were included in the study, 27 of them had laparoscopic
      cholecystectomy and 34 had open cholecystectomy. Cytokines [Interleukin-6
      Interleukin-1b, Tumor necrosis factor -a and Interleukin- 8] were measured in
      blood samples collected from the patients before, at and 24 hours post surgery,
      using commercially available kits. RESULTS: Interleukin-6 levels were
      significantly increased at 24 hours post surgery in the open cholecystectomy
      group of patients compared to the laparoscopic cholecystectomy group (P<0.04). No
      differences were found in the other cytokines levels (Interleukin-1b, tumor
      necrosis factor -a and Interleukin-8) between the open cholecystectomy and
      laparoscopic cholecystectomy groups. CONCLUSION: Laparoscopic cholecystectomy, a
      minimal access surgery, is associated with lower levels of the proinflammatory
      interleukin-6 cytokine compared to open cholecystectomy.

PMID- 11953772
TI  - Cochlear implants in deaf children.
AB  - OBJECTIVE: This investigation was aimed to determine the current status of
      sensorineural hearing loss in children from the provinces of the Kingdom Saudi
      Arabia and to report on those with severe to profound hearing loss who are in
      need of cochlear implant. METHODS: A comprehensive survey of 9540 Saudi children
      was carried out from September 1997 through to May 2000. The subjects were
      randomly selected from the 4 main provinces of the country. The main objective
      was to screen these children for hearing impairment. A survey team included an
      ear, nose and throat specialist, a nurse, a social worker and an audiologist. A
      questionnaire was completed; clinical examination and audiological assessment was
      performed. Those confirmed and in doubt cases were referred for further
      audiological and clinical assessment including computerized tomography scan and
      auditory brain stem response. RESULTS: The over all prevalence of hearing
      impairment was 13% (1241 out of 9540). Those with sensorineural hearing loss was
      142 (1.5%) and those with severe to profound (76-100 decibels loss) was 68 (0.7%)
      7 of them suffered from unilateral while 135 suffered from bilateral
      sensorineural hearing loss. CONCLUSION: The prevalence rate of severe to profound
      sensorineural hearing loss is high in our country compared to developed
      countries. Cochlear implant is a useful procedure for those with severe and
      profound sensorineural hearing loss but hearing aids must be tried first. There
      is definitely a requirement for additional hearing and speech centers to be
      available, which, are at least accessible in the big cities in each province.

PMID- 11953773
TI  - Vision screening of preschool children in Jeddah, Saudi Arabia.
AB  - OBJECTIVE: To determine the prevalence of Amblyopia and other refractive errors
      and to identify the factors associated with these disorders. METHODS: The study
      was carried out in Jeddah, Kingdom of Saudi Arabia, in 1999, on children enrolled
      in governmental kindergartens during the academic year 1419-1420H. Children were
      screened for Amblyopia, any child who failed to pass the screening examination,
      was referred to the ophthalmologist for complete examination. A 95% confidence
      interval was used to describe the prevalence of eye disorders. RESULTS: The
      number of children referred to the ophthalmologists was 102. Out of this figure,
      70% of children kept their appointment. Seventy-two children had decreased visual
      acuity of 20/30 or worse. The final diagnoses were as follows: Amblyopia in 8
      cases, which, give a prevalence rate of 1.3% (95% confidence intervals: 0.4-2.3);
      refractive errors in 50 cases (69%); strabismus in 4 cases (6%), duane syndrome
      in 2 cases (3%); and 8 children (11%) were completely normal. The positive
      predictive value of visual screening examination was 89%. We found no significant
      correlation between Amblyopia and the risk factors mentioned in the literature.
      CONCLUSION: Vision screening is very important and recommended to be carried out
      as part of periodic health examination for pre school children. It is cost
      effective, highly sensitive, acceptable and easy to be administered.

PMID- 11953774
TI  - A profile of childhood neuropathies at a university hospital in Oman.
AB  - OBJECTIVE: To analyze all cases of childhood neuropathies (under 14 years of age)
      and report on their profile, pattern, clinical features and management. METHODS:
      Children with acute flaccid paralysis, longstanding weakness of extremities,
      neuroregression and children receiving anti cancer drugs with symptoms suggestive
      of neuropathy were evaluated for evidence of peripheral neuropathy. The
      evaluation of children with acute flaccid paralysis was a prospective study from
      January 1992 through to December 2000. The rest of the patients were studied
      retrospectively from the hospital medical records, pediatric neurology outpatient
      clinic and the neurophysiology laboratory, Sultan Qaboos University Hospital, Al
      Khod, Oman RESULTS: Eighty-two (39 Male: 43 Female) children were found to have
      peripheral neuropathy. Acute Guillain-Barre [corrected] syndrome was the most
      common with 37 children (45.1%), followed by genetic neuropathies [hereditary
      motor and sensory neuropathy with 17 (20.7%), hereditary sensory and autonomic
      neuropathy with 2 (2.4%), hereditary spastic paraplegia associated neuropathy
      with 9 (11%) and metachromatic leucodystrophy with 9 (11%)]. Chronic inflammatory
      demyelinating neuropathy was seen in 5 (6.1%) and vincristine induced neuropathy
      in 3 (3.5%) children. CONCLUSION: Acute Guillain-Barre [corrected] syndrome is
      the most common neuropathy amongst the acquired neuropathies. The treatable
      neuropathies constituted 54.7% (45 children) and the preventable genetic
      neuropathies accounted for the remaining 45.3% (37 children)

PMID- 11953776
TI  - Hyperimmunoglobulin-E syndrome.
AB  - Two Saudi girls aged 8 years and 5 years were seen over a period of 6 years and 5
      years. Their clinical presentations consisted of recurrent bilateral otitis
      media, repeated episodes of tonsillitis and chest infection. Cultures from the
      ears grew on numerous occasions Staphylococcus aureus, Streptococcus pneumoniae,
      Pseudomonas aeroginosa, Proteus species and Providencia species. The 8-year-old
      had a serum IgE level of 1431 iu/L, with normal levels of other immunoglobulin
      classes. The 5-year-old had an immunoglobulin E value of 1119 iu/L with normal
      values of other immunoglobulin classes. Both were human immuno-deficiency virus
      negative and no other causes for elevated immunoglobulin E were found. The
      mothers of both cases had elevated immunoglobulin E levels of 1216 iu/L and 1992
      iu/L. Both fathers had normal IgE levels. A 13-year-old sibling of case one had a
      grossly elevated immunoglobulin E level of 2259 iu/L. She had diffuse lamellar
      icthyosis and recurrent episodes of chest infection and conjunctivitis. There was
      a good clinical response of patient one to monthly intravenous human
      immunoglobulin.

PMID- 11953775
TI  - Low aspirin use in diabetics.
AB  - OBJECTIVE: To determine the percentage of adult diabetics with cardiovascular
      disease, or risk factors for cardiovascular disease who are using aspirin, and to
      report on any differences between males and females, or Saudis and non-Saudis.
      METHODS: Medical records of diabetics seen at King Abdulaziz University Hospital
      during the period January 1998 through to December 2000 were analyzed. The
      following data were collected: patients age, sex, nationality, body mass index,
      duration of diabetes, history of cardiovascular disease, risk factors for
      cardiovascular disease (hypertension, hyperlipidemia, obesity, smoking, family
      history of ischemic heart disease) and aspirin use. RESULTS: A total of 550
      patients were studied with a mean age of 53 years and male: female ratio 1.1:1.
      Saudis constitute 260/550 (47%) of the study group. In patients with
      cardiovascular disease 110/174 (63%) were using aspirin versus 64/174 (37%) (p
      0.001). In patients with one or more risk factors for cardiovascular disease but
      no cardiovascular disease, aspirin was used in 27/223 (12%) versus 195/223 (88%)
      (p 0.0001). Aspirin was used by 85/291 (29%) male versus 56/259 (22%) females (p
      0.2). Sixty-three of 260 (24%) Saudis used aspirin versus 77/290 (27%) non-Saudis
      (p 0.7). CONCLUSION: Aspirin use is low in diabetics with cardiovascular disease
      and one or more risk factor of cardiovascular disease, with no significant
      difference between males and females, or Saudis and non-Saudis. Physicians should
      be encouraged to use aspirin more in diabetics for both primary and secondary
      prevention of cardiovascular disease.

PMID- 11953777
TI  - Clinicopathological aspects of Chediak-Higashi syndrome in the accelerated phase.
AB  - This report describes clinical and laboratory features of a case of Chediak
      Higashi syndrome that presented in the accelerated phase of the disorder. This
      female infant presented with a fever, marked neutropenia, large cytoplasmic
      granules in leukocytes and a constellation of features that suggested a virus
      associated hemophagocytic syndrome. The clinical course was marked by limited
      response to the therapeutic agents that included ascorbate, cytotoxic agents and
      granulocyte colony-stimulating factor.

PMID- 11953779
TI  - Lumbar azygos vein producing an azygos lobe in the right lung.
AB  - The continuation of the azygos vein with the inferior vena cava and a well
      demarcated azygos lobe of the right lung were detected during routine dissection
      of a 65-years-old white male cadaver. The azygos arch was found dilated and
      malpositioned to create an aberrant azygos fissure in the right superior lobe
      which, was occupied by a fold of parietal pleura. The developmental and clinical
      significance of the azygos lobe is discussed.

PMID- 11953778
TI  - Diabetes and infarcted papillary thyroid cancer.
AB  - A young black Jordanian lady who has type one diabetes, chronic diabetic
      complication and ischemic heart disease, presented with a picture of diabetic
      keto-acidosis, precipitated by an acute neck swelling. This was suggestive of
      acute suppurative thyroiditis with abscess formation causing compressive
      symptoms. This unfortunate patient had an eventful course despite aggressive
      treatment by antibiotics and surgery and then succumbed of an acute cardiac
      event. The operative tissue biopsy revealed an abscess in an infarcted papillary
      thyroid cancer. We believe this is a rare presentation of such an association
      with a fatal outcome.

PMID- 11953780
TI  - Ectopic pregnancy.

PMID- 11953781
TI  - Drug resistant Mycobacterium tuberculosis in Saudi Arabia.

PMID- 11953782
TI  - Allergic bronchopulmonary aspergillosis mimicking pulmonary tuberculosis.

PMID- 11953783
TI  - Serum sodium changes during and after transurethral prostatectomy.

PMID- 11953784
TI  - Commission on Macroeconomics and Health.

PMID- 11953785
TI  - Health and the economy: empowerment through evidence.

PMID- 11953787
TI  - Poverty and health sector inequalities.
AB  - Poverty and ill-health are intertwined. Poor countries tend to have worse health
      outcomes than better-off countries. Within countries, poor people have worse
      health outcomes than better-off people. This association reflects causality
      running in both directions: poverty breeds ill-health, and ill-health keeps poor
      people poor. The evidence on inequalities in health between the poor and non-poor
      and on the consequences for impoverishment and income inequality associated with
      health care expenses is discussed in this article. An outline is given of what is
      known about the causes of inequalities and about the effectiveness of policies
      intended to combat them. It is argued that too little is known about the impacts
      of such policies, notwithstanding a wealth of measurement techniques and
      considerable evidence on the extent and causes of inequalities.

PMID- 11953786
TI  - Modelling HIV/AIDS epidemics in Botswana and India: impact of interventions to
      prevent transmission.
AB  - OBJECTIVE: To describe a dynamic compartmental simulation model for Botswana and
      India, developed to identify the best strategies for preventing spread of
      HIV/AIDS. METHODS: The following interventions were considered: a behavioural
      intervention focused on female sex workers; a conventional programme for the
      treatment of sexually transmitted infections; a programme for the prevention of
      mother-to-child transmission; an antiretroviral treatment programme for the
      entire population, based on a single regimen; and an antiretroviral treatment
      programme for sex workers only, also based on a single regimen. FINDINGS: The
      interventions directed at sex workers as well as those dealing with sexually
      transmitted infections showed promise for long-term prevention of human
      immunodeficiency virus (HIV) infection, although their relative ranking was
      uncertain. In India, a sex worker intervention would drive the epidemic to
      extinction. In Botswana none of the interventions alone would achieve this,
      although the prevalence of HIV would be reduced by almost 50%. Mother-to-child
      transmission programmes could reduce HIV transmission to infants, but would have
      no impact on the epidemic itself. In the long run, interventions targeting sexual
      transmission would be even more effective in reducing the number of HIV-infected
      children than mother-to-child transmission programmes. Antiretroviral therapy
      would prevent transmission in the short term, but eventually its effects would
      wane because of the development of drug resistance. CONCLUSION: Depending on the
      country and how the antiretroviral therapy was targeted, 25-100% of HIV cases
      would be drug- resistant after 30 years of use.

PMID- 11953788
TI  - Health, nutrition and prosperity: a microeconomic perspective.
AB  - A positive correlation between health and economic prosperity has been widely
      documented, but the extent to which this reflects a causal effect of health on
      economic outcomes is very controversial. Two classes of evidence are examined.
      First, carefully designed random assignment studies in the laboratory and field
      provide compelling evidence that nutritional deficiency - particularly iron
      deficiency - reduces work capacity and, in some cases, work output. Confidence in
      these results is bolstered by a good understanding of the underlying biological
      mechanisms. Some random assignment studies indicate an improved yield from health
      services in the labour market. Second, observational studies suggest that general
      markers of nutritional status, such as height and body mass index (BMI), are
      significant predictors of economic success although their interpretation is
      confounded by the fact that they reflect influences from early childhood and
      family background. Energy intake and possibly the quality of the diet have also
      been found to be predictive of economic success in observational studies.
      However, the identification of causal pathways in these studies is difficult and
      involves statistical assumptions about unobserved heterogeneity that are
      difficult to test. Illustrations using survey data demonstrate the practical
      importance of this concern. Furthermore, failure to take into account the dynamic
      interplay between changes in health and economic status has led to limited
      progress being reported in the literature. A broadening of random assignment
      studies to measure the effects of an intervention on economic prosperity,
      investment in population-based longitudinal socioeconomic surveys, and
      application of emerging technologies for a better measure of health in these
      surveys will yield very high returns in improving our understanding of how health
      influences economic prosperity.

PMID- 11953789
TI  - Ethics in international health research: a perspective from the developing world.
AB  - Health research plays a pivotal role in addressing inequities in health and human
      development, but to achieve these objectives the research must be based on sound
      scientific and ethical principles. Although it is accepted that ethics play a
      central role in health research in developing countries, much of the recent
      debate has focused on controversies surrounding internationally sponsored
      research and has taken place largely without adequate participation of the
      developing countries. The relationship between ethical guidelines and
      regulations, and indigenously sponsored and public health research has not been
      adequately explored. For example, while the fundamental principles of ethical
      health research, such as community participation, informed consent, and shared
      benefits and burdens, remain sacrosanct other issues, such as standards of care
      and prior agreements, merit greater public debate within developing countries. In
      particular, the relationship of existing ethical guidelines to epidemiological
      and public health research merits further exploration. In order to support health
      research in developing countries that is both relevant and meaningful, the focus
      must be on developing health research that promotes equity and on developing
      local capacity in bioethics. Only through such proactive measures can we address
      the emerging ethical dilemmas and challenges that globalization and the genomics
      revolution will bring in their wake.

PMID- 11953790
TI  - Research-tool patents: issues for health in the developing world.
AB  - The patent system is now reaching into the tools of medical research, including
      gene sequences themselves. Many of the new patents can potentially preempt large
      areas of medical research and lay down legal barriers to the development of a
      broad category of products. Researchers must therefore consider redesigning their
      research to avoid use of patented techniques, or expending the effort to obtain
      licences from those who hold the patents. Even if total licence fees can be kept
      low, there are enormous negotiation costs, and one "hold-out" may be enough to
      lead to project cancellation. This is making it more difficult to conduct
      research within the developed world, and poses important questions for the future
      of medical research for the benefit of the developing world. Probably the most
      important implication for health in the developing world is the possible general
      slowing down and complication of medical research. To the extent that these
      patents do slow down research, they weaken the contribution of the global
      research community to the creation and application of medical technology for the
      benefit of developing nations. The patents may also complicate the granting of
      concessional prices to developing nations - for pharmaceutical firms that seek to
      offer a concessional price may have to negotiate arrangements with research-tool
      firms, which may lose royalties as a result. Three kinds of response are
      plausible. One is to develop a broad or global licence to permit the patented
      technologies to be used for important applications in the developing world. The
      second is to change technical patent law doctrines. Such changes could be
      implemented in developed and developing nations and could be quite helpful while
      remaining consistent with TRIPS. The third is to negotiate specific licence
      arrangements, under which specific research tools are used on an agreed basis for
      specific applications. These negotiations are difficult and expensive, requiring
      both scientific and legal skills. But they will be an unavoidable part of
      international medical research.

PMID- 11953791
TI  - Antimicrobial resistance: a global response.
AB  - Resistance to antimicrobial therapies reduces the effectiveness of these drugs,
      leading to increased morbidity, mortality, and health care expenditure. Because
      globalization increases the vulnerability of any country to diseases occurring in
      other countries, resistance presents a major threat to global public health, and
      no country acting on its own can adequately protect the health of its population
      against it. International collective action is therefore essential. Nevertheless,
      responsibility for health remains predominantly national. Consequently, there is
      a potentially significant disparity between the problems and solutions related to
      antimicrobial resistance and the institutions and mechanisms that are available
      to deal with them. This paper considers the capacity of national and
      international institutions and mechanisms to generate a collective response to
      antimicrobial resistance. Strategies for containing resistance are outlined, with
      particular reference to globally coordinated activities of countries. The
      adequacy of national and international responses to resistance is assessed, and
      the actions that international bodies could take to solve difficulties associated
      with present responses are highlighted. Approaches are suggested for securing
      international collective action for the containment of antimicrobial resistance.

PMID- 11953792
TI  - Basic patterns in national health expenditure.
AB  - Analysed in this paper are national health accounts estimates for 191 WHO Member
      States for 1997, using simple comparisons and linear regressions to describe
      spending on health and how it is financed. The data cover all sources - out-of
      pocket spending, social insurance contributions, financing from government
      general revenues and voluntary and employment-related private insurance -
      classified according to their completeness and reliability. Total health spending
      rises from around 2-3% of gross domestic product (GDP) at low incomes (< 1000 US
      dollars per capita) to typically 8-9% at high incomes (> 7000 US dollars).
      Surprisingly, there is as much relative variation in the share for poor countries
      as for rich ones, and even more relative variation in amounts in US dollars. Poor
      countries and poor people that most need protection from financial catastrophe
      are the least protected by any form of prepayment or risk-sharing. At low
      incomes, out-of-pocket spending is high on average and varies from 20-80% of the
      total; at high incomes that share drops sharply and the variation narrows.
      Absolute out-of-pocket expenditure nonetheless increases with income. Public
      financing increases faster, and as a share of GDP, and converges at high incomes.
      Health takes an increasing share of total public expenditure as income rises,
      from 5-6% to around 10%. This is arguably the opposite of the relation between
      total health needs and need for public spending, for any given combination of
      services. Within public spending, there is no convergence in the type of finance 
      general revenue versus social insurance. Private insurance is usually
      insignificant except in some rich countries.

PMID- 11953793
TI  - Effectiveness of community health financing in meeting the cost of illness.
AB  - How to finance and provide health care for the more than 1.3 billion rural poor
      and informal sector workers in low- and middle-income countries is one of the
      greatest challenges facing the international development community. This article
      presents the main findings from an extensive survey of the literature of
      community financing arrangements, and selected experiences from the Asia and
      Africa regions. Most community financing schemes have evolved in the context of
      severe economic constraints, political instability, and lack of good governance.
      Micro-level household data analysis indicates that community financing improves
      access by rural and informal sector workers to needed heath care and provides
      them with some financial protection against the cost of illness. Macro-level
      cross-country analysis gives empirical support to the hypothesis that risk
      sharing in health financing matters in terms of its impact on both the level and
      distribution of health, financial fairness and responsiveness indicators. The
      background research done for this article points to five key policies available
      to governments to improve the effectiveness and sustainability of existing
      community financing schemes. This includes: (a) increased and well-targeted
      subsidies to pay for the premiums of low-income populations; (b) insurance to
      protect against expenditure fluctuations and re-insurance to enlarge the
      effective size of small risk pools; (c) effective prevention and case management
      techniques to limit expenditure fluctuations; (d) technical support to strengthen
      the management capacity of local schemes; and (e) establishment and strengthening
      of links with the formal financing and provider networks.

PMID- 11953794
TI  - Debt relief and public health spending in heavily indebted poor countries.
AB  - The Heavily Indebted Poor Countries (HIPC) Initiative, which was launched in
      1996, is the first comprehensive effort by the international community to reduce
      the external debt of the world's poorest countries. The Initiative will generate
      substantial savings relative to current and past public spending on health and
      education in these countries. Although there is ample scope for raising public
      health spending in heavily indebted poor countries, it may not be advisable to
      spend all the savings resulting from HIPC resources for this purpose. Any
      comprehensive strategy for tackling poverty should also focus on improving the
      efficiency of public health outlays and on reallocating funds to programmes that
      are most beneficial to the poor. In order to ensure that debt relief increases
      poverty-reducing spending and benefits the poor, all such spending, not just that
      financed by HIPC resources, should be tracked. This requires that countries
      improve all aspects of their public expenditure management. In the short run,
      heavily indebted poor countries can take some pragmatic tracking measures based
      on existing public expenditure management systems, but in the longer run they
      should adopt a more comprehensive approach so as to strengthen their budget
      formulation, execution, and reporting systems.

PMID- 11953795
TI  - Trade in health services.
AB  - In light of the increasing globalization of the health sector, this article
      examines ways in which health services can be traded, using the mode-wise
      characterization of trade defined in the General Agreement on Trade in Services.
      The trade modes include cross- border delivery of health services via physical
      and electronic means, and cross-border movement of consumers, professionals, and
      capital. An examination of the positive and negative implications of trade in
      health services for equity, efficiency, quality, and access to health care
      indicates that health services trade has brought mixed benefits and that there is
      a clear role for policy measures to mitigate the adverse consequences and
      facilitate the gains. Some policy measures and priority areas for action are
      outlined, including steps to address the "brain drain"; increasing investment in
      the health sector and prioritizing this investment better; and promoting linkages
      between private and public health care services to ensure equity. Data
      collection, measures, and studies on health services trade all need to be
      improved, to assess better the magnitude and potential implications of this
      trade. In this context, the potential costs and benefits of trade in health
      services are shaped by the underlying structural conditions and existing
      regulatory, policy, and infrastructure in the health sector. Thus, appropriate
      policies and safeguard measures are required to take advantage of globalization
      in health services.

PMID- 11953796
TI  - Round table. The work of the Commission on Macroeconomics and Health.

PMID- 11953797
TI  - An economist's view of health. Interview by John Maurice.

PMID- 11953798
TI  - Renaming the NCDs.

PMID- 11953799
TI  - Arsenic and hypertension in Bangladesh.

PMID- 11953801
TI  - Indian women impose unofficial drinking fines.

PMID- 11953800
TI  - African children talk faster with iron.

PMID- 11953804
TI  - Minimum standard of care defined for HIV patients with cancer.

PMID- 11953808
TI  - Microbial diversity and activity along the forefields of two receding glaciers.
AB  - Forefields of two receding glaciers were sampled along either a 150 or 200 m long
      transect at identical spatial intervals for assessment of soil microbial activity
      and community diversity trends. The forefields belonged to the Dammaglacier
      (forefield area is 157 ha, 2000 m above sea level) and Rotfirnglacier (100 ha,
      2200 m) and at the time of sampling were receding at an estimated rate of 8 and
      10 m yr(-1) over the past 5 years, respectively. Direct counting of bacteria
      (DAPI staining), assessment of dehydrogenase activity (DH), and fluorescein
      diacetate hydrolysis activity (FDA) were performed to estimate bacteria number
      and soil microbial activity. Along the Dammaglacier forefield (from youngest to
      oldest soil), bacteria number (8.21 x 10(7) to 1.49 x 10(9) cells g(-1) soil), DH
      activity (0 to 61 mg TTC reduced g(-1) soil h(-1)), and FDA activity (0 to 100 mg
      fluorescein produced g-1 soil h-1) increased, suggesting the development of
      microbial populations increasing in number and activity. The Rotfirn forefield
      exhibited similar trends per gram of soil in bacteria number (1.13 x 10(8) to
      5.93 x 10(9) cells), DH activity (0 to 36 mg TTC reduced), and FDA activity (2 to
      70 mg fluorescein produced), but with more variability among samples than the
      Damma forefield samples. Molecular assessment of bacterial diversity included
      denaturing gradient gel electrophoresis (DGGE) and ribosomal intergenic spacer
      analysis (RISA) of soil DNA. DGGE and RISA revealed that the composition and
      succession of bacterial populations were different in both forefields. Comparison
      of Shannon diversity index values indicated that all populations sampled from the
      Damma forefield were significantly different (p < 0.05). Conversely, similar
      populations existed in the Rotfirn forefield succession. Overall, the results
      indicate that diverse bacterial assemblages increasing in number and activity
      characterize these glacier forefield soils with both forefield successions
      exhibiting differing modes of bacterial community establishment.

PMID- 11953809
TI  - Effect of nitrogen and phosphorus on growth of toxic and nontoxic Microcystis
      strains and on intracellular microcystin concentrations.
AB  - The growth and intracellular microcystin concentration of two hepatotoxic and two
      nontoxic axenic Microcystis strains were measured in batch cultures with variable
      nitrogen (0.84-84 mg L(-1)) and phosphorus (0.05-5.5 mg L(-1)) concentrations.
      Growth was estimated by measuring dry weight, optical density, chlorophyll a, and
      cellular protein concentration. Microcystin concentrations in cells and in
      culture medium were measured by HPLC analysis. Both nontoxic strains needed less
      nutrients for their growth at low nutrient concentrations. With high nutrient
      concentrations the toxic strains grew better than the nontoxic strains. Growth
      and intracellular microcystin concentration did not correlate in the hepatotoxic
      strains. Multivariate regression analysis together with mathematical modeling
      revealed a significant interactive effect of nitrogen and phosphorus, which
      partly explains the controversial results obtained in previous studies. In this
      study we have shown that variation of nitrogen and phosphorus concentrations
      influence the growth and the microcystin production of Microcystis strains and
      that the strains differ in their response to nutrients. High levels of nitrogen
      and phosphorus in freshwaters may favor the growth of toxic Microcystis strains
      over nontoxic ones.

PMID- 11953811
TI  - Disruptive visions:  surgeon responsibility during the era of change.

PMID- 11953810
TI  - Abundance and biomass of heterotrophic flagellates, and factors controlling their
      abundance and distribution in sediments of Botany Bay.
AB  - The abundance and biomass of heterotrophic flagellates were estimated monthly in
      sediments of Botany Bay during March 1999-February 2000. The annual abundance and
      biomass were in the ranges of 0.46-4.70 x 10(5) cells/cm(3) and of 0.30-8.61
      micro g C/cm(3), respectively. The majority of heterotrophic flagellates (93
      100%) were less than 10 mm in length and few flagellates were larger than 10 mm.
      Of the total microbial carbon biomass, heterotrophic flagellates made up about 5%
      (but at times up to 35%). The contribution of heterotrophic flagellates varied
      from month to month, and among the sites. The abundance of heterotrophic
      flagellates was negatively correlated with sediment grain size and positively
      correlated with the abundance of bacteria, algae (autotrophic flagellates and
      diatoms), and their probable grazers. A best subsets regression analysis showed
      that bacterial and algal abundance are the most important factors controlling the
      abundance of heterotrophic flagellates. When the previously reported grazing
      rates on bacteria were applied, heterotrophic flagellates would consume a maximum
      of 64% of bacterial standing stock daily in Botany Bay, suggesting that
      heterotrophic flagellates are important as bacterivores. However, the importance
      of heterotrophic flagellate grazing probably varies significantly among the sites
      and from month to month.

PMID- 11953812
TI  - Anaerobic biooxidation of Fe(II) by Dechlorosoma suillum.
AB  - Anaerobic microbial oxidation of Fe(II) was only recently discovered and very
      little is known about this metabolism. We recently demonstrated that several
      dissimilatory perchlorate-reducing bacteria could utilize Fe(II) as an electron
      donor under anaerobic conditions. Here we report on a more in-depth analysis of
      Fe(II) oxidation by one of these organisms, Dechlorosoma suillum. Similarly to
      most known nitrate-dependent Fe(II) oxidizers, D. suillum did not grow
      heterotrophically or lithoautotrophically by anaerobic Fe(II) oxidation. In the
      absence of a suitable organic carbon source, cells rapidly lysed even though
      nitrate-dependent Fe(II) oxidation was still occurring. The coupling of Fe(II)
      oxidation to a particular electron acceptor was dependent on the growth
      conditions of cells of D. suillum. As such, anaerobically grown cultures of D.
      suillum did not mediate Fe(II) oxidation with oxygen as the electron acceptor,
      while conversely, aerobically grown cultures did not mediate Fe(II) oxidation
      with nitrate as the electron acceptor. Anaerobic washed cell suspensions of D.
      suillum rapidly produced an orange/brown precipitate which X-ray diffraction
      analysis identified as amorphous ferric oxyhydroxide or ferrihydrite. This is
      similar to all other identified nitrate-dependent Fe(II) oxidizers but is in
      contrast to what is observed for growth cultures of D. suillum, which produced a
      mixed-valence Fe(II)-Fe(III) precipitate known as green rust. D. suillum rapidly
      oxidized the Fe(II) content of natural sediments. Although the form of ferrous
      iron in these sediments is unknown, it is probably a component of an insoluble
      mineral, as previous studies indicated that soluble Fe(II) is a relatively minor
      form of the total Fe(II) content of anoxic environments. The results of this
      study further enhance our knowledge of a poorly understood form of microbial
      metabolism and indicate that anaerobic Fe(II) oxidation by D. suillum is
      significantly different from previously described forms of nitrate-dependent
      microbial Fe(II) oxidation.

PMID- 11953813
TI  - A Bayesian re-assessment of two Phase II trials of gemcitabine in metastatic
      nasopharyngeal cancer.
AB  - The Simon two-stage minimax design is a popular statistical design used in Phase
      II clinical trials. The analysis of the data arising from the design typically
      involves the use of frequentist statistics. This paper presents an alternative,
      Bayesian, approach to the design and analysis of Phase II clinical trials. In
      particular, we consider how a Bayesian approach could have affected the design,
      analysis and interpretation of two parallel Phase II trials of the National
      Cancer Centre Singapore, on the activity of gemcitabine in chemotherapy-naive and
      in previously treated patients with metastatic nasopharyngeal carcinoma. We begin
      by explaining the Bayesian methodology and contrasting it with the frequentist
      approach. We then carry out a Bayesian analysis of the trial results. The
      conclusions drawn using the Bayesian approach were in general agreement with
      those obtained from the frequentist analysis. However they had the advantage of
      allowing for different and potentially more useful interpretations to be made
      regarding the trial results, as well as for the incorporation of external sources
      of information. In particular, using a Bayesian trial design, we were able to
      take into account the results of the parallel trial results when deciding whether
      to continue each trial beyond the interim stage.

PMID- 11953814
TI  - Transhiatal vs extended transthoracic resection in oesophageal carcinoma:
      patients' utilities and treatment preferences.
AB  - To assess patients' utilities for health state outcomes after transhiatal or
      transthoracic oesophagectomy for oesophageal cancer and to investigate the
      patients' treatment preferences for either procedure. The study group consisted
      of 48 patients who had undergone either transhiatal or transthoracic
      oesophagectomy. In an interview they were presented with eight possible health
      states following oesophagectomy. Visual Analogue Scale and standard gamble
      techniques were used to measure utilities. Treatment preference for either
      transhiatal or transthoracic oesophagectomy was assessed. Highest scores were
      found for the patients' own current health state (Visual Analogue Scale: 0.77;
      standard gamble: 0.97). Lowest scores were elicited for the health state
      "irresectable tumour" (Visual Analogue Scale: 0.13; standard gamble: 0.34). The
      Visual Analogue Scale method produced lower estimates (P<0.001) than the standard
      gamble method for all health states. Most patient characteristics and clinical
      factors did not correlate with the utilities. Ninety-five per cent of patients
      who underwent a transthoracic procedure and 52% of patients who underwent a
      transhiatal resection would prefer the transthoracic treatment. No significant
      associations between any patient characteristics or clinical characteristics and
      treatment preference were found. Utilities after transhiatal or transthoracic
      oesophagectomy were robust because they generally did not vary by patient or
      clinical characteristics. Overall, most patients preferred the transthoracic
      procedure.

PMID- 11953815
TI  - Serum levels of the angiogenic factor pleiotrophin in relation to disease stage
      in lung cancer patients.
AB  - Pleiotrophin is a heparin-binding growth factor involved in the differentiation
      and proliferation of neuronal tissue during embryogenesis, and also secreted by
      melanoma and breast carcinoma cells. Pleiotrophin exhibits mitogenic and
      angiogenic properties and has been shown to influence the vascular supply,
      expansion and metastasis of tumour cells. Our aim was to study the serum and
      plasma concentrations of pleiotrophin and the classical angiogenic growth factor
      vascular endothelial growth factor. Using a specific ELISA-test we studied
      patients with small cell lung cancer (n=63), and patients with non-small cell
      lung cancer (n=22) in comparison to healthy control subjects (n=41). In most of
      the lung cancer patients (81%), we found serum levels of pleiotrophin above those
      of control subjects (P<0.001). Of the 63 small cell lung cancer patients in the
      study pleiotrophin serum levels were elevated in 55 cases (87%) and in 14 cases
      (63%) of the 22 non-small cell lung cancer patients. Pleiotrophin mean serum
      concentrations were 10.8-fold higher in the tumour patient group as compared to
      the control group (P<0.001). Furthermore, pleiotrophin serum levels correlated
      positively with the stage of disease and inversely with the response to therapy.
      Plasma vascular endothelial growth factor concentrations were elevated in only in
      28.6% of small cell lung cancer and 45.5% of non-small cell lung cancer patients
      by an average of 2.3-fold. Quite strikingly, there was no apparent correlation
      between the plasma vascular endothelial growth factor concentration and the stage
      of disease. Our study suggests that pleiotrophin may be an early indicator of
      lung cancer and might be of use in monitoring the efficacy of therapy, which
      needs to be confirmed by larger studies.

PMID- 11953816
TI  - Increased pre-therapeutic serum vascular endothelial growth factor in patients
      with early clinical relapse of osteosarcoma.
AB  - To investigate the clinical significance of circulating angiogenic factors,
      especially in association with early relapse of osteosarcoma, we quantified pre
      therapeutic levels of vascular endothelial growth factor, basic fibroblast growth
      factor and placenta growth factor in the sera of 16 patients with osteosarcoma
      using an enzyme-linked immunosorbent assay. After a 1-year follow-up, the serum
      level of angiogenic factors was analysed with respect to microvessel density of
      the biopsy specimen and clinical disease relapse. The serum vascular endothelial
      growth factor levels were positively correlated with the microvessel density with
      statistical significance (P=0.004; Spearman rank correlation) and also
      significantly higher in seven patients who developed pulmonary metastasis than
      the remaining nine patients without detectable disease relapse (P=0.0009; The
      Mann-Whitney U-test). In contrast, the serum levels of basic fibroblast growth
      factor or placenta growth factor failed to show significant correlation with the
      microvessel density or relapse of the disease. Although there was no significant
      correlation between serum vascular endothelial growth factor levels and the
      tumour volume, the serum vascular endothelial growth factor levels were
      significantly higher in patients with a vascular endothelial growth factor
      positive tumour than those with a vascular endothelial growth factor-negative
      tumour. These findings suggest that the pre-therapeutic serum vascular
      endothelial growth factor level reflects the angiogenic property of primary
      tumour and may have a predictive value on early disease relapse of osteosarcoma.

PMID- 11953817
TI  - Axillary node status in breast cancer patients prior to surgery by imaging with
      Tc-99m humanised anti-PEM monoclonal antibody, hHMFG1.
AB  - In early breast cancer axillary nodes are usually impalpable and over 50% of such
      patients may have an axillary clearance when no nodes are involved. This work
      identifies axillary node status by imaging with a Tc-99m radiolabelled anti
      Polymorphic Epithelial Mucin, humanised monoclonal antibody (human milk fat
      globule 1), prior to surgery in 30 patients. Change detection analysis of image
      data with probability mapping is undertaken. A specificity of 93% and positive
      predictive value of 92% (both 100% if a second cancer in the axilla with negative
      nodes is considered) were found. A strategy for combining negative imaging with
      the sentinel node procedure is presented.

PMID- 11953818
TI  - The human ovarian surface epithelium is an androgen responsive tissue.
AB  - The pathogenesis of epithelial ovarian cancer remains unclear. From
      epidemiological studies raised levels of androgens have been implicated to
      increase the risk of developing the disease. The purpose of this study was to
      determine the responses of normal human ovarian surface epithelium to androgens.
      We have established primary cultures of human ovarian surface epithelium from
      patients undergoing oophorectomy for benign disease. Total RNA was isolated from
      these cultures and expression of mRNA encoding for the androgen receptor was
      demonstrated using reverse transcriptase polymerase chain reaction. The presence
      of androgen receptor in sections of normal ovary was also investigated using an
      antibody against androgen receptor. The effects of androgens on DNA synthesis and
      cell death were determined. Eight out of eight (100%) cultures expressed mRNA
      encoding the androgen receptor. The presence of androgen receptor in ovarian
      surface epithelium of sections of normal ovaries was demonstrated in all
      sections. Mibolerone, a synthetic androgen, caused a significant stimulation of
      DNA synthesis in 5 out of 9 (55%) cultures when used at a concentration of 1 nM.
      Mibolerone also caused a significant decrease in cell death in 2 out of 5 (40%)
      cultures tested. We have demonstrated that the ovarian surface epithelium is an
      androgen responsive tissue and that androgens can cause an increase in
      proliferation and a decrease in cell death. These findings have important
      implications for the pathophysiology of ovarian carcinogenesis.

PMID- 11953819
TI  - Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory
      protein, in pancreatic adenocarcinoma.
AB  - Survivin is unique for its expression in human malignancies but not in normal
      adult cells. It has been implicated in sensitisation to chemotherapy and as a
      prognostic marker in several common cancers. Immunohistochemistry for Survivin,
      P53 and BCL-2 expression as well as cell proliferative index (Ki-67) and
      apoptosis index (TUNEL) was conducted on 52 pancreatic and 12 ampullary
      adenocarcinomas. Survivin was detected in the cytoplasm of carcinoma cells in 46
      (88%) of pancreatic tumours. P53 and BCL-2 were detected in 54% and 12% of
      pancreatic tumours, respectively. Proliferative index was 26.2+/-10.5% and
      apoptosis index was 1.38+/-0.69%. Prevalence of Survivin expression was
      significantly higher in P53-positive than in P53-negative cases (P=0.05) but was
      not associated with BCL-2 expression. Incrementally higher weighted scores of
      Survivin expression were associated with increased proliferative index (P=0.001).
      Furthermore, there was linear correlation between increased proliferative index
      and higher apoptosis index (P<0.001). Surprisingly, higher scores of Survivin
      expression were associated with increased apoptosis index (P=0.007). Survival
      characteristics were not influenced by Survivin, P53 or BCL-2 expression,
      apoptosis index or proliferative index. Ampullary carcinoma showed Survivin
      expression in 83% of cases. However, unlike pancreatic carcinoma, there was no
      correlation between Survivin and P53 expression or proliferative index. In
      conclusion, Survivin is expressed in the majority of pancreatic adenocarcinomas
      and correlates with both cellular proliferation and apoptosis. Molecular
      manipulation of Survivin expression may enhance chemotherapy and radiation
      therapy for pancreatic cancer.

PMID- 11953820
TI  - Analysis of the cytochrome c-dependent apoptosis apparatus in cells from human
      pancreatic carcinoma.
AB  - Defects in the apoptotic system are likely to play a role in tumorigenesis.
      Pancreatic carcinoma cells are extremely resistant to apoptosis induction by
      chemotherapy suggesting that the apoptosis machinery is faulty. We investigated
      the integrity of the cytochrome c-dependent apoptotic apparatus in 10 human
      pancreatic carcinoma cell lines. Expression of Apaf-1, caspase-3, -6, -7, -8 and 
      9, Hsp-70 and XIAP was detected in all cell lines. The expression levels of Apaf
      1 and caspase-8 were homogenous in all cell lines whereas differences in
      expression of other caspases were seen. In cytosolic fractions, all investigated
      caspases were processed in response to cytochrome c but the extent of processing
      varied between the cell lines. No stringent correlation between the amount of
      processing of caspase-9 and effector caspases was seen. Cytochrome c-induced
      effector caspase activity was quantitated by enzyme assay. Especially at low
      concentrations of added cytochrome c, this response varied greatly between the
      cell lines. These data demonstrate that the apoptotic system downstream of the
      mitochondria is qualitatively intact in pancreatic carcinoma. They further show
      that the response to cytochrome c can be quantitated in a cell-free system and
      that determinants other than mere expression of apoptotic molecules can regulate
      cytochrome c-induced apoptosis.

PMID- 11953821
TI  - Prostate-Specific Ets (PSE) factor: a novel marker for detection of metastatic
      breast cancer in axillary lymph nodes.
AB  - Prostate Specific Ets factor is a recently identified transcriptional activator
      that is overexpressed in prostate cancer. To determine whether this gene is
      overexpressed in breast cancer, we performed a virtual Northern blot using data
      available online at the Cancer Genome Anatomy Project website. Ninety-five SAGE
      libraries were probed with a unique sequence tag to the Prostate Specific Ets
      gene. The results indicate that Prostate Specific Ets is expressed in 14 out of
      15 breast cancer libraries (93%), nine out of 10 prostate cancer libraries (90%),
      three out of 40 libraries from other cancers (7.5%), and four out of 30 normal
      tissue libraries (13%). To determine the possibility that the Prostate Specific
      Ets gene is a novel marker for detection of metastatic breast cancer in axillary
      lymph nodes, quantitative real-time RT-PCR analyses were performed. The mean
      level of Prostate Specific Ets expression in lymph nodes containing metastatic
      breast cancer (n=22) was 410-fold higher than in normal lymph node (n=51). A
      receiver operator characteristic curve analysis indicated that Prostate Specific
      Ets was overexpressed in 18 out of 22 lymph nodes containing metastatic breast
      cancer (82%). The receiver operator characteristic curve analysis also indicated
      that the diagnostic accuracy of the Prostate Specific Ets gene for detection of
      metastatic breast cancer in axillary lymph nodes was 0.949. These results provide
      evidence that Prostate Specific Ets is a potentially informative novel marker for
      detection of metastatic breast cancer in axillary lymph nodes, and should be
      included in any study that involves molecular profiling of breast cancer.

PMID- 11953822
TI  - Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the
      breast.
AB  - Up to 50% of recurrences of ductal carcinoma in situ of the breast are associated
      with invasive carcinoma but no pathological or molecular features have yet been
      found to predict for the development of invasive disease. For a tumour to invade,
      it requires the formation of new blood vessels. Previous studies have described a
      vascular rim around ducts involved by ductal carcinoma in situ, raising the
      possibility that the characteristics of periductal vascularisation may be
      important in determining transformation from in situ to invasive disease.
      Periductal vascular density and phenotype were determined using morphometry and a
      panel of anti-endothelial antibodies (von Willebrand factor, CD31, CD141 and
      CD34) and related to the presence of invasive carcinoma and other histological
      features. Compared to normal lobules, pure ductal carcinoma in situ exhibited a
      greater density of CD34+ and CD31+ vessels but a decrease in those that were
      immunopositive for vWF, indicating a difference in phenotype and in density.
      Ductal carcinoma in situ associated with invasive carcinoma showed a profile of
      vascular immunostaining similar to that of pure ductal carcinoma in situ but
      there were significantly greater numbers of CD34+ and CD141+ vessels and fewer
      staining for vWF. There was a significant negative correlation between vascular
      density and both the cross-sectional areas of the ducts involved and the extent
      of the necrosis of the tumour they contained. A correlation between vascular
      density and nuclear grade was also noted, being highest in the intermediate
      grade. The greater density of CD34+ and CD141+ vessels around ductal carcinoma in
      situ associated with invasive carcinoma could reflect a greater predisposition to
      invade but a direct effect of co-existent invasive carcinoma cannot entirely be
      ruled out in the present study. The relationship between vascular density, grade,
      duct size and nuclear grade suggests that periductal angiogenesis increases with
      tumour growth rate but is unable to keep pace with the most rapidly growing
      lesions.

PMID- 11953823
TI  - Caveolin-1 overexpression is an early event in the progression of papillary
      carcinoma of the thyroid.
AB  - Caveolin-1 is a major structural component of caveolae, which are plasma membrane
      microdomains implicated in the regulation of intracellular signalling pathways.
      Previous in vitro and in vivo studies on the function of caveolin-1 in carcinoma
      showed controversial results, indicating that the physiological role of caveolin
      1 varies according to the origin of carcinoma. In this study, we investigated
      caveolin-1 expression in thyroid neoplasms by means of immunohistochemistry using
      a rabbit polyclonal antibody against caveolin-1. Normal follicular cells did not
      express caveolin-1. In papillary carcinoma, caveolin-1 expression was observed in
      high incidence, and especially in microcancer (less than 1.0 cm in diameter),
      caveolin-1 was positive in all cases except one. In undifferentiated (anaplastic)
      carcinoma, its incidence was significantly reduced. On the other hand, all cases
      of follicular carcinoma and adenoma were classified as negative for caveolin-1.
      These results suggest that caveolin-1 may play a role predominantly in the early
      phase of papillary carcinoma, whereas it has little influence on follicular
      tumours.

PMID- 11953825
TI  - Genetic aberrations detected by comparative genomic hybridisation in vulvar
      cancers.
AB  - Squamous cell carcinoma of the vulva is a disease of significant clinical
      importance, which arises in the presence or absence of human papillomavirus. We
      used comparative genomic hybridisation to document non-random chromosomal gains
      and losses within human papillomavirus positive and negative vulvar cancers. Gain
      of 3q was significantly more common in human papillomavirus-positive cancers
      compared to human papillomavirus-negative cancers. The smallest area of gain was
      3q22-25, a chromosome region which is frequently gained in other human
      papillomavirus-related cancers. Chromosome 8q was more commonly gained in human
      papillomavirus-negative compared to human papillomavirus-positive cancers. 8q21
      was the smallest region of gain, which has been identified in other, non-human
      papillomavirus-related cancers. Chromosome arms 3p and 11q were lost in both
      categories of vulvar cancer. This study has demonstrated chromosome locations
      important in the development of vulvar squamous cell carcinoma. Additionally,
      taken together with previous studies of human papillomavirus-positive cancers of
      other anogenital sites, the data indicate that one or more oncogenes important in
      the development and progression of human papillomavirus-induced carcinomas are
      located on 3q. The different genetic changes seen in human papillomavirus
      positive and negative vulvar squamous cell carcinomas support the
      clinicopathological data indicating that these are different cancer types.

PMID- 11953824
TI  - Isolation of a SIR-like gene, SIR-T8, that is overexpressed in thyroid carcinoma
      cell lines and tissues.
AB  - We used subtractive library screening to identify the changes that occur in gene
      expression during thyroid cell neoplastic transformation. Complementary DNA from
      normal thyroid cells (HTC 2) was subtracted from a complementary DNA library
      constructed from a human thyroid papillary carcinoma cell line. The library was
      screened for genes upregulated in human thyroid papillary carcinoma cell line
      cells, and several cDNA clones were isolated. One of these clones has a sirtuin
      core and high homology with the human silent information regulator protein
      family. This clone, designated "SIR-T8", was overexpressed in human thyroid
      carcinoma cell lines and tissues, but not in adenomas. The human SIR-T8 protein
      has a molecular weight of 39 kDa and is primarily located in the cytoplasm under
      the nuclear membrane. The SIR-T8 gene is located on chromosome 17q25-1.

PMID- 11953826
TI  - Genetic abnormalities detected in ependymomas by comparative genomic
      hybridisation.
AB  - Using comparative genomic hybridisation, we have analysed genetic imbalance in a
      series of 86 ependymomas from children and adults. Tumours were derived from
      intracranial and spinal sites, and classified histologically as classic,
      anaplastic or myxopapillary. Ependymomas showing a balanced profile were
      significantly (P<0.0005) more frequent in children than adults. Profiles
      suggesting intermediate ploidy were common (44% of all tumours), and found more
      often (P<0.0005) in tumours from adults and the spinal region. Loss of 22q was
      the most common specific abnormality, occurring in 50% of spinal (medullary)
      ependymomas and 26% of tumours overall. Genetic profiles combining loss of 22q
      with other specific abnormalities--gain of 1q, loss of 6q, loss of 10q/10, loss
      of 13, loss of 14q/14--varied according to site and histology. In particular, we
      showed that classic ependymomas from within the cranium and spine have distinct
      genetic profiles. Classic and anaplastic ependymomas with gain of 1q tended to
      occur in the posterior fossa of children and to behave aggressively. Our
      extensive data on ependymomas demonstrate significant associations between
      genetic aberrations and clinicopathological variables, and represent a starting
      point for further biological and clinical studies.

PMID- 11953827
TI  - Down-regulation of Lsm1 is involved in human prostate cancer progression.
AB  - Elucidation of genetic alterations is an approach to understanding the underlying
      molecular mechanisms of progression of human prostate cancers. We have searched
      for genes differentially expressed in advanced prostate cancers using cDNA
      representational difference analysis, and thereby isolated the Lsm1 as one of
      down-regulated gene. An Lsm1 expression vector was transfected into PC3 cells,
      normally featuring down-regulated Lsm1, and four transfectants were established.
      No differences in morphology or cell proliferation were evident in comparison
      with parent PC3 or PC3/mock-transfectants. In contrast, significant suppression
      of invasive potential or metastatic ability of Lsm1 transfectants was observed in
      the Matrigel chemoinvasion assay and in nude mice, respectively. With human
      prostate cancers, almost all of informative prostatectomised cases without
      neoadjuvant therapy showed allelic retention in the Lsm1 region, whereas
      refractory cancers frequently showed allelic loss in this region. No critical
      gene mutations were found in open reading frame of Lsm1 in prostate cancers
      examined by PCR-SSCP analysis, including localised and refractory cancers. These
      results suggest that Lsm1 is deeply involved in prostate cancer progression
      through its down-regulation, independent of any gene mutation.

PMID- 11953828
TI  - Solid stress facilitates spheroid formation: potential involvement of hyaluronan.
AB  - When neoplastic cells grow in confined spaces in vivo, they exert a finite force
      on the surrounding tissue resulting in the generation of solid stress. By growing
      multicellular spheroids in agarose gels of defined mechanical properties, we have
      recently shown that solid stress inhibits the growth of spheroids and that this
      growth-inhibiting stress ranges from 45 to 120 mmHg. Here we show that solid
      stress facilitates the formation of spheroids in the highly metastatic Dunning
      R3327 rat prostate carcinoma AT3.1 cells, which predominantly do not grow as
      spheroids in free suspension. The maximum size and the growth rate of the
      resulting spheroids decreased with increasing stress. Relieving solid stress by
      enzymatic digestion of gels resulted in gradual loss of spheroidal morphology in
      8 days. In contrast, the low metastatic variant AT2.1 cells, which grow as
      spheroids in free suspension as well as in the gels, maintained their spheroidal
      morphology even after stress removal. Histological examination revealed that most
      cells in AT2.1 spheroids are in close apposition whereas a regular matrix
      separates the cells in the AT3.1 gel spheroids. Staining with the hyaluronan
      binding protein revealed that the matrix between AT3.1 cells in agarose contained
      hyaluronan, while AT3.1 cells had negligible or no hyaluronan when grown in free
      suspension. Hyaluronan was found to be present in both free suspensions and
      agarose gel spheroids of AT2.1. We suggest that cell-cell adhesion may be
      adequate for spheroid formation, whereas solid stress may be required to form
      spheroids when cell-matrix adhesion is predominant. These findings have
      significant implications for tumour growth, invasion and metastasis.

PMID- 11953829
TI  - Selection and characterisation of a phage-displayed human antibody (Fab) reactive
      to the lung resistance-related major vault protein.
AB  - The major vault protein is the main component on multimeric vault particles, that
      are likely to play an essential role in normal cell physiology and to be
      associated with multidrug resistance of tumour cells. In order to unravel the
      function of vaults and their putative contribution to multidrug resistance,
      specific antibodies are invaluable tools. Until now, only conventional major
      vault protein-reactive murine monoclonal antibodies have been generated, that are
      most suitable for immunohistochemical analyses. The phage display method allows
      for selection of human antibody fragments with potential use in clinical
      applications. Furthermore, cDNA sequences encoding selected antibody fragments
      are readily identified, facilitating various molecular targeting approaches. In
      order to obtain such human Fab fragments recognising major vault protein we used
      a large non-immunized human Fab fragment phage library. Phages displaying major
      vault protein-reactive Fabs were obtained through several rounds of selection on
      major vault protein-coated immunotubes and subsequent amplification in TG1 E coli
      bacteria. Eventually, one major vault protein-reactive clone was selected and
      further examined. The anti-major vault protein Fab was found suitable for
      immunohistochemical and Western blot analysis of tumour cell lines and human
      tissues. BIAcore analysis showed that the binding affinity of the major vault
      protein-reactive clone almost equalled that of the murine anti-major vault
      protein Mabs. The cDNA sequence of this human Fab may be exploited to generate an
      intrabody for major vault protein-knock out studies. Thus, this human Fab
      fragment should provide a valuable tool in elucidating the contribution(s) of
      major vault protein/vaults to normal physiology and cellular drug resistance
      mechanisms.

PMID- 11953830
TI  - Apoptosis is associated with triacylglycerol accumulation in Jurkat T-cells.
AB  - Magnetic resonance spectroscopy is increasingly used as a non-invasive method to
      investigate apoptosis. Apoptosis was induced in Jurkat T-cells by Fas mAb. (1)H
      magnetic resonance spectra of live cells showed an increase in methylene signal
      as well as methylene/methyl ratio of fatty acid side chains at 5 and 24 h
      following induction of apoptosis. To explain this observation, (1)H magnetic
      resonance spectra of cell extracts were investigated. These demonstrated a 70.0+/
      7.0%, 114.0+/-8.0% and 90.0+/-5.0% increase in the concentration of
      triacylglycerols following 3, 5 and 7 h of Fas mAb treatment (P<0.05). Confocal
      microscopy images of cells stained with the lipophilic dye Nile Red demonstrated
      the presence of lipid droplets in the cell cytoplasm. Quantification of the
      stained lipids by flow cytometry showed a good correlation with the magnetic
      resonance results (P > or =0.05 at 3, 5 and 7 h). (31)P magnetic resonance
      spectra showed a drop in phosphatidylcholine content of apoptosing cells,
      indicating that alteration in phosphatidylcholine metabolism could be the source
      of triacylglycerol accumulation during apoptosis. In summary, apoptosis is
      associated with an early accumulation of mobile triacylglycerols mostly in the
      form of cytoplasmic lipid droplets. This is reflected in an increase in the
      methylene/methyl ratio which could be detected by magnetic resonance
      spectroscopy.

PMID- 11953831
TI  - Mechanism of action for N-substituted benzamide-induced apoptosis.
AB  - We have analysed the mechanism of action for induction of apoptosis by N
      substituted benzamides using declopramide as a lead compound. We show here that
      declopramide at doses above 250 microM in the mouse 70Z/3 pre-B cell line or in
      the human promyeolocytic cancer cell line HL60 induced cytochrome c release into
      the cytosol and caspase-9 activation. The broad spectrum caspase inhibitor
      zVADfmk and caspase-9 inhibitor zLEDHfmk inhibited apoptosis and improved cell
      viability when administrated to cells 1 h before exposure to declopramide,
      whereas the caspase-8 inhibitor zIEDHfmk had less effect. Also, the over
      expression of Bcl-2 by transfection in 70Z/3 cells inhibited declopramide-induced
      apoptosis. Prior to the induction of apoptosis, a G(2)/M cell cycle block was
      induced by declopramide. The cell cycle block was also observed in the presence
      of broad spectrum caspase inhibitor zVADfmk and in a transfectant expressing high
      levels of Bcl-2. Furthermore, while p53 was induced in 70Z/3 cells by
      declopramide, neither the apoptotic mechanism nor the G(2)/M cell cycle block
      were dependent on p53 activation since both effects were also seen in p53
      deficient HL60 cells after addition of declopramide.

PMID- 11953832
TI  - Cancer testis antigens expression in mesothelioma: role of DNA methylation and
      bioimmunotherapeutic implications.
AB  - Recent evidences suggest that malignant mesothelioma may be sensitive to
      immunotherapy; however, little is known about malignant mesothelioma-associated
      tumour antigens. Focusing on cancer/testis antigens, the expression of well
      characterised immunogenic tumour-associated antigens was investigated in
      malignant mesothelioma cells. At variance with MAGE-4 and NY-ESO-1, malignant
      mesothelioma cells frequently expressed MAGE-1, -2 and -3, GAGE 1-2, GAGE 1-6,
      SSX-2 and SSX 1-5, and distinct malignant mesothelioma cells concomitantly
      expressed at least four cancer/testis antigens. Additionally, the tumour
      associated antigens RAGE-1 was expressed at high levels in both benign and
      malignant mesothelial cells. Lastly, treatment with the DNA hypomethylating agent
      5-aza-2'-deoxycytidine induced and up-regulated the expression of the
      cancer/testis antigen examined in malignant mesothelioma cells. Overall, these
      findings strongly suggest that cancer/testis antigens-based immunotherapy may
      represent a suitable therapeutic approach to malignant mesothelioma, and foresee
      the clinical use of 5-aza-2'-deoxycytidine to design new chemo-immunotherapeutic
      strategies in malignant mesothelioma patients.

PMID- 11953833
TI  - Consumption of an omega-3 fatty acids product, INCELL AAFA, reduced side-effects
      of CPT-11 (irinotecan) in mice.
AB  - INCELL AAFA, an omega-3 polyunsaturated fatty acid product containing a high
      concentration of long chain fatty acids, was tested for its ability to ameliorate
      the harmful side effects of CPT-11 chemotherapy including: leukopenia, anaemia,
      asthenia, weight loss and liver involvement. Four groups of mice were fed an AIN
      76 diet modified to contain: 10% w/w corn oil (CO), 0% AAFA; 9% CO, 1% AAFA; 8%
      CO, 2% AAFA; or 7% CO, 3% AAFA. After 2 weeks on the diets, half of the mice
      received CPT-11 chemotherapy (60 mg kg(-1) q 4 days, i.v.) the rest of the mice
      received vehicle for 2 weeks. It was found that 2% AAFA in the diet of the CPT-11
      treated mice: decreased apoptotic figures in the duodenal crypts; markedly
      suppressed the inflammatory eicosanoid, prostaglandin E(2) in the liver;
      prevented liver hypertrophy; improved white blood cell counts; significantly
      increased red blood cell counts; decreased numbers of CPT-11 induced immature red
      blood cell and micronuclei in red blood cells of the peripheral blood; increased
      eicosapentaenoic acid and docosahexaenoic acid in liver cell membranes and
      maintained normal grooming behaviour. Thus 2% AAFA in the diet reduced the side
      effects of CPT-11 treatment in mice.

PMID- 11953834
TI  - The role of reperfusion injury in photodynamic therapy with 5-aminolaevulinic
      acid--a study on normal rat colon.
AB  - Reperfusion injury can occur when blood flow is restored after a transient period
      of ischaemia. The resulting cascade of reactive oxygen species damages tissue.
      This mechanism may contribute to the tissue damage produced by 5-aminolaevulinic
      acid-induced photodynamic therapy, if this treatment temporarily depletes oxygen
      in an area that is subsequently reoxygenated. This was investigated in the normal
      colon of female Wistar rats. All animals received 200 mg kg(-1) 5-aminolaevulinic
      acid intravenously 2 h prior to 25 J (100 mW) of 628 nm light, which was
      delivered continuously or fractionated (5 J/150 second dark interval/20 J).
      Animals were recovered following surgery, killed 3 days later and the
      photodynamic therapy lesion measured macroscopically. The effects of reperfusion
      injury were removed from the experiments either through the administration of
      free radical scavengers (superoxide dismutase (10 mg kg(-1)) and catalase (7.5 mg
      kg(-1)) in combination) or allopurinol (an inhibitor of xanthine oxidase (50 mg
      kg(-1))). Prior administration of the free radical scavengers and allopurinol
      abolished the macroscopic damage produced by 5-aminolaevulinic acid photodynamic
      therapy in this model, regardless of the light regime employed. As the specific
      inhibitor of xanthine oxidase (allopurinol) protected against photodynamic
      therapy damage, it is concluded that reperfusion injury is involved in the
      mechanism of photodynamic therapy in the rat colon.

PMID- 11953835
TI  - Inhibition of endothelial cell functions and of angiogenesis by the metastasis
      inhibitor NAMI-A.
AB  - NAMI-A is a ruthenium-based compound with selective anti-metastasis activity in
      experimental models of solid tumours. We studied whether this activity was
      dependent on anti-angiogenic ability of NAMI-A. We thus investigated its in vitro
      effects on endothelial cell functions necessary for angiogenesis to develop, as
      well as its in vivo effects in the chick embryo chorioallantoic membrane model.
      Endothelial cell proliferation, chemotaxis, and secretion of the matrix-degrading
      enzyme metalloproteinase-2 were inhibited by NAMI-A in a dose-dependent manner,
      and without morphologic signs of cell apoptosis or necrosis. Lastly, NAMI-A
      displayed a dose-dependent in vivo anti-angiogenic activity in the
      chorioallantoic membrane model. These data suggest that the anti-angiogenic
      activity of NAMI-A can contribute to its anti-metastatic efficacy in mice bearing
      malignant solid tumours.

PMID- 11953837
TI  - Nuclear distribution of porphobilinogen deaminase (PBGD) in glioma cells: a
      regulatory role in cancer transformation?
AB  - Recently, considerable interest has been directed to red-fluorescence
      photodiagnosis of brain and other tumours during surgery using the protoporphyrin
      IX natural precursor, 5-aminolaevulinic acid. In the present study we focused on
      the role of the rate-limiting enzyme porphobilinogen deaminase in glioma C6 cell
      activity, differentiation and sub-cellular distribution. Over-expression of the
      human housekeeping porphobilinogen deaminase in the glioma cells, using the
      housekeeping-porphobilinogen deaminase plasmid, induced a G1 cell cycle
      attenuation accompanied by increases in enzyme activity and c6 differentiation
      toward astrocytes. Visualisation of subcellular localisation of the
      porphobilinogen deaminase using the independent techniques of fluorescence immuno
      staining with specific anti-human porphobilinogen deaminase antibodies and
      cellular expression of porphobilinogen deaminase fused to green fluorescent
      protein, revealed (unexpectedly) a major fraction of porphobilinogen deaminase in
      the nucleus and only a minor fraction in the cytoplasm. Both C and N terminals of
      porphobilinogen deaminase fused to green fluorescent protein revealed a major
      fraction of the newly synthesized fused porphobilinogen deaminase in the nucleus.
      Furthermore, newborn rat brain cells grown in a primary culture showed the same
      localisation pattern of porphobilinogen deaminase in the nuclei. Stimulation of
      C6 glioma cell differentiation by butyrate induced a marked decrease in
      porphobilinogen deaminase both in the nucleus and in the cytoplasm as determined
      by Western blotting and fluorescence immuno-localisation. These findings suggest
      a possible dual role for housekeeping porphobilinogen deaminase in fast dividing
      glioma cells, one related to the porphyrin synthesis pathway and another coupled
      to nuclear function, which might be linked to tumorigenesis.

PMID- 11953836
TI  - Circadian optimisation of irinotecan and oxaliplatin efficacy in mice with
      Glasgow osteosarcoma.
AB  - The relevance of circadian rhythms in irinotecan and oxaliplatin tolerability was
      investigated with regard to antitumour activity. Mice bearing Glasgow
      osteosarcoma (GOS) received single agent irinotecan (50 or 60 mg kg(-1) per day)
      or oxaliplatin (4 or 5.25 mg kg(-1) per day) at one of six dosing times expressed
      in hours after light onset (3, 7, 11, 15, 19 or 23 hours after light onset).
      Irinotecan (50 mg kg(-1) per day) and oxaliplatin (4 or 5.25 mg kg(-1) per day)
      were given 1 min apart at 7 or 15 hours after light onset, or at their respective
      times of best tolerability (7 hours after light onset for irinotecan and 15 hours
      after light onset for oxaliplatin) or worst tolerability (15 hours after light
      onset for irinotecan and 7 hours after light onset for oxaliplatin). Tumour
      growth rate was nearly halved and per cent increase in estimated life span (%
      ILS) was - doubled in the mice receiving irinotecan at 7 hours after light onset
      as compared to 15 hours after light onset (P<0.05). Results of similar magnitude
      were obtained with oxaliplatin for both endpoints, yet with 7 hours after light
      onset corresponding to least efficacy and 15 hours after light onset to best
      efficacy (P<0.05). Irinotecan addition to oxaliplatin proved therapeutic benefit
      only if the schedule consisted of irinotecan administration at 7 hours after
      light onset and oxaliplatin delivery at 15 hours after light onset, i.e. when
      both drugs were given near their respective "best" circadian times. These would
      correspond to the middle of the night for irinotecan and the middle of the day
      for oxaliplatin in humans.

PMID- 11953839
TI  - Responses to docetaxel plus vinorelbine in metastatic breast cancer patients
      failing high-dose chemotherapy.

PMID- 11953841
TI  - Clues from hypercalcaemia.

PMID- 11953838
TI  - TNF-alpha is involved in activating DNA fragmentation in skeletal muscle.
AB  - Intraperitoneal administration of 100 microg kg(-1) (body weight) of tumour
      necrosis factor-alpha to rats for 8 consecutive days resulted in a significant
      decrease in protein content, which was concomitant with a reduction in DNA
      content. Interestingly, the protein/DNA ratio was unchanged in the skeletal
      muscle of the tumour necrosis factor-alpha-treated animals as compared with the
      non-treated controls. Analysis of muscle DNA fragmentation clearly showed
      enhanced laddering in the skeletal muscle of tumour necrosis factor-alpha-treated
      animals, suggesting an apoptotic phenomenon. In a different set of experiments,
      mice bearing a cachexia-inducing tumour (the Lewis lung carcinoma) showed an
      increase in muscle DNA fragmentation (9.8-fold) as compared with their non-tumour
      bearing control counterparts as previously described. When gene-deficient mice
      for tumour necrosis factor-alpha receptor protein I were inoculated with Lewis
      lung carcinoma, they were also affected by DNA fragmentation; however the
      increase was only 2.1-fold. These results suggest that tumour necrosis factor
      alpha partly mediates DNA fragmentation during experimental cancer-associated
      cachexia.

PMID- 11953842
TI  - Translation initiation and its deregulation during tumorigenesis.
AB  - Regulation of protein synthesis at the level of translation initiation is
      fundamentally important for the control of cell proliferation under normal
      physiological conditions. Conversely, misregulation of protein synthesis is
      emerging as a major contributory factor in cancer development. Most bulk protein
      synthesis is initiated via recognition of the mRNA 5' cap and subsequent
      recognition of the initiator AUG codon by a directional scanning mechanism.
      However, several key regulators of tumour development are translated by a cap
      independent pathway. Here we review eukaryotic translation initiation, its
      regulation and the ways in which this regulation can break down during
      tumorigenesis.

PMID- 11953843
TI  - Reduced 5-FU clearance in a patient with low DPD activity due to heterozygosity
      for a mutant allele of the DPYD gene.
AB  - 5-fluorouracil pharmacokinetics, dihydropyrimidine dehydrogenase-activity and DNA
      sequence analysis were compared between a patient with extreme 5-fluorouracil
      induced toxicity and six control patients with normal 5-fluorouracil related
      symptoms. Patients were treated for colorectal cancer and received chemotherapy
      consisting of leucovorin 20 mg m(-2) plus 5-fluorouracil 425 mg m(-2). Blood
      sampling was carried out on day 1 of the first cycle. The 5-fluorouracil area
      under the curve(0-->3h) in the index patient was 24.1 mg h l(-1) compared to
      9.8+/-3.6 (range 5.4-15.3) mg h l(-1) in control patients. The 5-fluorouracil
      clearance was 520 ml min(-1) vs 1293+/-302 (range 980-1780) ml min(-1) in
      controls. The activity of dihydropyrimidine dehydrogenase in mononuclear cells
      was lower in the index patient (5.5 nmol mg h(-1)) compared to the six controls
      (10.3+/-1.6, range 8.0-11.7 nmol mg h(-1)). Sequence analysis of the
      dihydropyrimidine dehydrogenase gene revealed that the index patient was
      heterozygous for a IVS14+1G>A point mutation. Our results indicate that the
      inactivation of one dihydropyrimidine dehydrogenase allele can result in a strong
      reduction in 5-fluorouracil clearance, causing severe 5-fluorouracil induced
      toxicity.

PMID- 11953844
TI  - Patient delay and stage of diagnosis among breast cancer patients in Germany -- a
      population based study.
AB  - Early diagnosis is a tenet in oncology and should enable early treatment with the
      expectation of improved outcome. Extent and determinants of patient delay of
      diagnosis in breast cancer patients and its impact on stage of disease were
      examined in a population based study among female breast cancer patients in
      Germany. Two hundred and eighty-seven women, aged 18 to 80 years with newly
      diagnosed invasive symptomatic breast cancer, were interviewed with respect to
      the diagnostic process. Patient delay was defined as time from onset of first
      symptoms to first consultation of a doctor. Median patient delay was 16 days
      among symptomatic patients. Eighteen per cent of all breast cancer patients
      waited longer than 3 months before consulting a physician. Long patient delay was
      associated with old age, history of a benign mastopathy, obesity, and indices of
      health behaviour such as not knowing a gynaecologist for out-patient care and non
      participation in general health screening examinations. A strong association
      between patient delay and stage at diagnosis was observed for poorly
      differentiated tumours. These results suggest that at risk groups for delaying
      consultation can be identified and that a substantial proportion of late stage
      diagnoses of poorly differentiated breast cancer cases could be avoided if all
      patients with breast cancer symptoms would present to a doctor within 1 month.

PMID- 11953845
TI  - Prognostic significance of a complete pathological response after induction
      chemotherapy in operable breast cancer.
AB  - Only a few papers have been published concerning the incidence and outcome of
      patients with a pathological complete response after cytotoxic treatment in
      breast cancer. The purpose of this retrospective study was to assess the outcome
      of patients found to have a pathological complete response in both the breast and
      axillary lymph nodes after neoadjuvant chemotherapy for operable breast cancer.
      Our goal was also to determine whether the residual pathological size of the
      tumour in breast could be correlated with pathological node status. Between 1982
      and 2000, 451 consecutive patients were registered into five prospective phase II
      trials. After six cycles, 396 patients underwent surgery with axillary dissection
      for 277 patients (69.9%). Pathological response was evaluated according to the
      Chevallier's classification. At a median follow-up of 8 years, survival was
      analysed as a function of pathological response. A pathological complete response
      rate was obtained in 60 patients (15.2%) after induction chemotherapy. Breast
      tumour persistence was significantly related to positive axillary nodes (P=5.10(
      6)). At 15 years, overall survival and disease-free survival rates were
      significantly higher in the group who had a pathological complete response than
      in the group who had less than a pathological complete response (P=0.047 and
      P=0.024, respectively). In the absence of pathological complete response and
      furthermore when there is a notable remaining pathological disease, axillary
      dissection is still important to determine a major prognostic factor and
      subsequently, a second non cross resistant adjuvant regimen or high dose
      chemotherapy could lead to a survival benefit.

PMID- 11953846
TI  - The presence of bone marrow cytokeratin-immunoreactive cells does not predict
      outcome in gastric cancer patients.
AB  - The independent prognostic significance of isolated tumour cells in bone marrow
      is still a matter of debate. This study evaluated the possible association of
      bone marrow micrometastases with tumour progression and prognosis in patients
      affected by gastric cancer. Bone marrow aspirates from both iliac crests were
      obtained from 114 consecutive patients operated on for gastric cancer. The
      specimens were stained with monoclonal antibody CAM 5.2 which reacts
      predominantly with cytokeratin filaments 8 and 19. Among 114 cases analysed, 33
      cases (29%) had cytokeratine-positive cells in the bone marrow. There was no
      significant relationship between the presence of bone marrow micrometastases and
      site, depth of tumour invasion, lymph node metastases, presence of metastases.
      Patients with cytokeratine-positive cells had a trend towards a diffuse type
      histology (P=0.06). Among the 88 curatively resected patients, median survivals
      were 40 months and 36 months for cytokeratine-negative and cytokeratine-positive
      subsets respectively (P=0.9). Recurrence of the disease was observed in 39 cases
      (44.3%); 11 of 24 (45.8%) in the cytokeratine-positive subset and 28 of 64
      (43.7%) in the cytokeratine-negative subset. In conclusion in our experience the
      presence of cytokeratine-positive cells in the bone marrow of curatively resected
      gastric cancer patients did not affect outcome and its independent prognostic
      significance remains to be proven before its official acceptance in the TNM
      classification.

PMID- 11953847
TI  - Cancer Research UK procedures in manufacture and toxicology of radiotracers
      intended for pre-phase I positron emission tomography studies in cancer patients.
AB  - Radiolabelled compounds formulated for injection (radiopharmaceuticals), are
      increasingly being employed in drug development studies. These can be used in
      tracer amounts for either pharmacokinetic or pharmacodynamic studies. Such
      radiotracer studies can also be carried out early in man, even prior to
      conventional Phase I clinical testing. The aim of this document is to describe
      procedures for production and safety testing of oncology radiotracers developed
      for imaging by positron emission tomography in cancer patients. We propose
      strategies for overcoming the inability to produce compounds in sufficient
      quantities via the radiosynthetic routes for full chemical characterisation and
      toxicology testing including (i) independent confirmation as far as possible that
      the stable compound associated with the radiopharmaceutical is identical to the
      non-labelled compound, (ii) animal toxicity studies with > or = 10 times
      (typically 100 times) the intended tracer dose in humans scaled by body surface
      area, and (iii) patient monitoring during the radiotracer positron emission
      tomography clinical trial.

PMID- 11953848
TI  - Do not attempt resuscitation decisions in a cancer centre: addressing difficult
      ethical and communication issues.
AB  - Talking to patients about 'Do Not Attempt Resuscitation' decisions is difficult
      for many doctors. Communication about 'Do Not Attempt Resuscitation' decisions
      should occur as part of a wider discussion of treatment goals at an earlier stage
      in the patient's illness. A doctor should not initiate any treatment, including
      cardio-pulmonary resuscitation if he/she does not believe it will benefit the
      patient. An ethical framework is offered which may be of practical help in
      clarifying decision-making.

PMID- 11953849
TI  - Age-specific incidence rates for cytogenetically-defined subtypes of acute
      myeloid leukaemia.
AB  - It is generally considered that most cancers arise following the accumulation of
      several genetic events and that as a consequence its incidence increases with
      age. We report a cytogenetic subgroup of acute myeloid leukaemia whose incidence
      is independent of age. This observation indicates that acute myeloid leukaemia
      can develop via multiple pathways, and underlines the importance of cytogenetics
      in understanding this disease.

PMID- 11953850
TI  - Day-care, early common infections and childhood acute leukaemia: a multicentre
      French case-control study.
AB  - We conducted a case-control study to investigate the role of early infections in
      the aetiology of childhood acute leukaemias. The study included 280 incident
      cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic
      leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital,
      catchment area of the hospital and ethnic origin. Data were obtained from
      standardised face-to-face interviews of the mothers. The interviews included
      questions on early common infections, day-care attendance, breast-feeding, birth
      order and infantile diseases. Odds ratios were estimated using an unconditional
      regression model including the stratification variables, parental socio-economic
      status and perinatal characteristics. Birth order was not associated with
      childhood leukaemia (acute lymphoblastic or acute non-lymphoblastic). A
      statistically-significant inverse association was observed between childhood
      leukaemia and day-care attendance (odds ratio=0.6, 95% Confidence Interval=(0.4
      1.0)), repeated early common infections (> or = 4 per year before age two, odds
      ratio=0.6 (0.4-1.0)), surgical procedures for ear-nose-throat infections before
      age two (odds ratio=0.5 (0.2-1.0)) and prolonged breast-feeding (> or = 6 months,
      odds ratio=0.5 (0.2-1.0)). In the multivariate model including day-care
      attendance, early common infections and breast-feeding, results concerning breast
      feeding remained unchanged. A statistically significant interaction between day
      care attendance and repeated early common infections was observed. When the
      interaction was taken into account, the simple effects of day-care and early
      common infections disappeared (odds ratio=1.1 (0.5-2.3) and odds ratio=0.8 (0.5
      1.3), respectively) while the joint effect of day-care attendance and early
      common infections was negatively associated with childhood leukaemia (odds
      ratio=0.3 (0.1-0.8)). All the above associations were observed both for acute
      lymphoblastic leukaemia and acute non-lymphoblastic leukaemia. Our results
      support Greaves' hypothesis, even though they are not specific of common
      leukaemia.

PMID- 11953851
TI  - An infectious aetiology for childhood brain tumours? Evidence from space-time
      clustering and seasonality analyses.
AB  - To investigate whether infections or other environmental exposures may be
      involved in the aetiology of childhood central nervous system tumours, we have
      analysed for space-time clustering and seasonality using population-based data
      from the North West of England for the period 1954 to 1998. Knox tests for space
      time interactions between cases were applied with fixed thresholds of close in
      space, <5 km, and close in time, <1 year apart. Addresses at birth and diagnosis
      were used. Tests were repeated replacing geographical distance with distance to
      the Nth nearest neighbour. N was chosen such that the mean distance was 5 km.
      Data were also examined by a second order procedure based on K-functions. Tests
      for heterogeneity and Edwards' test for sinusoidal variation were applied to
      examine changes of incidence with month of birth or diagnosis. There was strong
      evidence of space-time clustering, particularly involving cases of astrocytoma
      and ependymoma. Analyses of seasonal variation showed excesses of cases born in
      the late Autumn or Winter. Results are consistent with a role for infections in a
      proportion of cases from these diagnostic groups. Further studies are needed to
      identify putative infectious agents.

PMID- 11953852
TI  - Childhood malignancy and maternal diabetes or other auto-immune disease during
      pregnancy.
AB  - Among 4380 children born in 1987-1997 of women with a diagnosis of diabetes and
      alive at the age of one, 10 were registered in the Swedish Cancer Registry before
      the end of 1998. The odds ratio for having a childhood cancer after maternal
      diabetes, stratified for year of birth, maternal age, parity, multiple birth, and
      500 g birth weight class was 2.25 (95%CI 1.22-4.15). Among 5842 children born
      during the period 1973-1997 whose mothers had other auto-immune diseases (SLE,
      rheumatoid arthritis, Crohn, ulcerous colitis, multiple sclerosis or
      thyroiditis), the number of observed childhood cancers (9) was close to that
      expected (8.5). Maternal diabetes but not other auto-immune diseases may be a
      risk factor for childhood cancer.

PMID- 11953853
TI  - Gallstones, cholecystectomy, and the risk for developing pancreatic cancer.
AB  - We examined the relation between gallstones, cholecystectomy, and the development
      of pancreatic cancer in the Nurses' Health Study and the Health Professionals
      Follow-up Study. Among 104,856 women and 48,928 men without cancer at baseline,
      we documented 349 cases of pancreatic cancer during up to 16 years of follow-up.
      Participants were classified according to a history of gallstones or
      cholecystectomy. The age-adjusted relative risk of pancreatic cancer following
      cholecystectomy or diagnosis of gallstones was 1.31 (95% CI, 0.93-1.83). However,
      adjustment for other pancreatic cancer risk factors attenuated the association
      (RR=1.11, 95% CI, 0.78-1.56); this risk did not increase with increasing time
      following cholecystectomy or gallstones. Gallstones or cholecystectomy do not
      appear to be significant risk factors for pancreatic cancer.

PMID- 11953855
TI  - Identifying pre-post chemotherapy differences in gene expression in breast
      tumours: a statistical method appropriate for this aim.
AB  - Although widely used for the analysis of gene expression microarray data, cluster
      analysis may not be the most appropriate statistical technique for some study
      aims. We demonstrate this by considering a previous analysis of microarray data
      obtained on breast tumour specimens, many of which were paired specimens from the
      same patient before and after chemotherapy. Reanalysing the data using
      statistical methods that appropriately utilise the paired differences for
      identification of differentially expressed genes, we find 17 genes that we can
      confidently identify as more expressed after chemotherapy than before. These
      findings were not reported by the original investigators who analysed the data
      using cluster analysis techniques.

PMID- 11953854
TI  - A pooled analysis of 10 case-control studies of melanoma and oral contraceptive
      use.
AB  - Data regarding the effects of oral contraceptive use on women's risk of melanoma
      have been difficult to resolve. We undertook a pooled analysis of all case
      control studies of melanoma in women completed as of July 1994 for which
      electronic data were available on oral contraceptive use along with other
      melanoma risk factors such as hair colour, sun sensitivity, family history of
      melanoma and sun exposure. Using the original data from each investigation (a
      total of 2391 cases and 3199 controls), we combined the study-specific odds
      ratios and standard errors to obtain a pooled estimate that incorporates inter
      study heterogeneity. Overall, we observed no excess risk associated with oral
      contraceptive use for 1 year or longer compared to never use or use for less than
      1 year (pooled odds ratio (pOR)=0.86; 95% CI=0.74-1.01), and there was no
      evidence of heterogeneity between studies. We found no relation between melanoma
      incidence and duration of oral contraceptive use, age began, year of use, years
      since first use or last use, or specifically current oral contraceptive use. In
      aggregate, our findings do not suggest a major role of oral contraceptive use on
      women's risk of melanoma.

PMID- 11953856
TI  - Fibroblast growth factor 8 is expressed at higher levels in lactating human
      breast and in breast cancer.
AB  - Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been
      found to be associated with breast and prostate cancer. Following our finding
      that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we
      have undertaken an immunohistochemistry study of fibroblast growth factor 8
      expression in a series of human breast tissues and other normal tissues. Our
      findings confirm increased expression of fibroblast growth factor 8 in malignant
      breast tissue but also show significant fibroblast growth factor 8 expression in
      non-malignant breast epithelial cells. No significant difference in fibroblast
      growth factor 8 expression was found between different grades of ductal
      carcinoma, lobular carcinoma and ductal carcinoma in-situ or cancer of different
      oestrogen receptor, progesterone receptor or nodal status. The highest levels of
      fibroblast growth factor 8 expression were found in lactating breast tissues and
      fibroblast growth factor 8 was also detected in human milk. A survey of other
      normal tissues showed that fibroblast growth factor 8 is expressed in the
      proliferative cells of the dermis and epithelial cells in colon, ovary fallopian
      tube and uterus. Fibroblast growth factor 8 appears to be expressed in several
      organs in man and appears to have an importance in lactation.

PMID- 11953857
TI  - Dominant negative knockout of p53 abolishes ErbB2-dependent apoptosis and permits
      growth acceleration in human breast cancer cells.
AB  - We previously reported that the ErbB2 oncoprotein prolongs and amplifies growth
      factor signalling by impairing ligand-dependent downregulation of hetero
      oligomerised epidermal growth factor receptors. Here we show that treatment of
      A431 cells with different epidermal growth factor receptor ligands can cause
      growth inhibition to an extent paralleling ErbB2 tyrosine phosphorylation. To
      determine whether such growth inhibition signifies an interaction between the
      cell cycle machinery and ErbB2-dependent alterations of cell signalling kinetics,
      we used MCF7 breast cancer cells (which express wild-type p53) to create
      transient and stable ErbB2 transfectants (MCF7-B2). Compared with parental cells,
      MCF7-B2 cells are characterised by upregulation of p53, p21(WAF) and Myc,
      downregulation of Bcl2, and apoptosis. In contrast, MCF7-B2 cells co-transfected
      with dominant negative p53 (MCF7-B2/Delta p53) exhibit reduced apoptosis and
      enhanced growth relative to both parental MCF7-B2 and control cells. These data
      imply that wild-type p53 limits survival of ErbB2-overexpressing breast cancer
      cells, and suggest that signals of varying length and/or intensity may evoke
      different cell outcomes depending upon the integrity of cell cycle control genes.
      We submit that acquisition of cell cycle control defects may play a permissive
      role in ErbB2 upregulation, and that the ErbB2 overexpression phenotype may in
      turn select for the survival of cells with p53 mutations or other tumour
      suppressor gene defects.

PMID- 11953858
TI  - Experience with International Neuroblastoma Staging System and Pathology
      Classification.
AB  - The International Neuroblastoma Staging System and Pathology Classification were
      proposed in 1988 and in 1999, respectively, but their clinical value has not yet
      been fully studied in new patients. Six hundred and forty-four patients with
      neuroblastoma treated between January 1995 and December 1999 were analysed by
      these classifications. The 4-year overall survival rate of patients <12 months of
      age with INSS stages 1, 2A, 2B, 3 and 4S disease was 98.5%, which was
      significantly higher than the 73.1% rate in stage 4 patients <12 months
      (P<0.0001). When patients were > or = 12 months, the 4-year overall survival rate
      of patients with neuroblastoma at 1, 2A, 2B and 3 stages was 100% and that of
      patients at stage 4 was 48.5% (P<0.0001). As to the International Neuroblastoma
      Pathology Classification histology, the 4-year overall survival rate was 98.8% in
      patients with favourable histology and 60.7% in those with unfavourable histology
      in the <12 months group (P<0.0001). In the > or = 12 months group, the 4-year
      oral survival of patients with favourable histology was 95.3% and that of
      patients with unfavourable histology was 50.6% (P<0.0001). Among biological
      factors, MYCN amplification, DNA diploidy and 1p deletions were significantly
      associated with poor prognosis in patients <12 months, as were MYCN amplification
      and DNA diploidy in patients > or = 12 months of age. Multivariate analysis
      showed that the INSS stage (stage 4 vs other stages) and International
      Neuroblastoma Pathology Classification histology (unfavourable vs favourable)
      were significantly and independently associated with the survival of patients
      undergoing treatment, stratified by age, stage and MYCN amplification (P=0.0002
      and P=0.0051, respectively).

PMID- 11953859
TI  - The molecular pathology of p53 in primitive neuroectodermal tumours of the
      central nervous system.
AB  - One hundred and one pre-treatment primary central primitive neuroectodermal
      tumours were analysed for the expression of p53 protein by immunohistochemistry
      using the monoclonal antibody DO-7. The staining intensity was classified into
      four groups: strong, medium, weak and negative and strong staining intensity was
      associated with the poorest survival. DNA sequencing of the p53 gene was
      performed in 28 cases representing all four staining groups. Mutations were found
      in only three of the strong staining tumours suggesting that DNA mutations were
      not common events and that in the majority of the tumours with over-expressed
      p53, the protein was likely to be wild-type. Results of immunohistochemistry
      showed a significantly positive relationship between the expression of p53 and
      Bax and Bcl-2 proteins, but not Waf-1. Multivariate analyses supported the
      prognostic value of p53 immunostaining in central primitive neuroectodermal
      tumours and also of age and gender of patients.

PMID- 11953860
TI  - Nuclear beta-catenin expression is closely related to ulcerative growth of
      colorectal carcinoma.
AB  - Although most colorectal cancer develops based on the adenoma-adenocarcinoma
      sequence, morphologically, colorectal cancer is not a homogeneous disease entity.
      Generally, there are two distinct morphological types: polypoid and ulcerative
      colorectal tumours. Previous studies have demonstrated that K-ras codon 12
      mutations are preferentially associated with polypoid growth of colorectal
      cancer; however, little is known about the molecular mechanism that determines
      ulcerative growth of colorectal cancer. beta-catenin complex plays a critical
      role both in tumorigenesis and morphogenesis. We examined the differential
      expression of beta-catenin and its related factors among different types of
      colorectal cancer in order to determine any relationship with gross tumour
      morphology. Immunohistochemical staining of beta-catenin, E-cadherin and MMP-7
      was performed on 51 tumours, including 26 polypoid tumours and 25 ulcerative
      tumours. Protein truncation tests and single-strand conformational polymorphism
      for mutation of the adenomatous polyposis coli tumour suppressor gene, as well as
      single-strand conformational polymorphism for the mutation of beta-catenin exon 3
      were also done. Nuclear expression of beta-catenin was observed in 18 out of 25
      (72%) cases of ulcerative colorectal cancer and seven out of 26 (26.9%) cases of
      polypoid colorectal cancer. A significant relationship of nuclear beta-catenin
      expression with ulcerative colorectal cancer was found (P<0.001). However, this
      finding was independent of adenomatous polyposis coli tumour suppressor gene
      mutation and E-cadherin expression. Together with previous data, we propose that
      different combinations of genetic alterations may underlie different
      morphological types of colorectal cancer. These findings should be taken into
      consideration whenever developing a new genetic diagnosis or therapy for
      colorectal cancer.

PMID- 11953861
TI  - Photodynamic therapy of DNA mismatch repair-deficient and -proficient tumour
      cells.
AB  - Loss of DNA mismatch repair is a common finding in hereditary nonpolyposis colon
      cancer as well as in many types of sporadic human tumours. DNA mismatch repair
      deficient cells have been reported to be resistant to many chemotherapeutic
      agents and to radiotherapy, and to have the potential of rapidly acquiring
      additional mutations leading to tumour progression. Photodynamic therapy is a new
      treatment modality using light to activate a photosensitiser that preferentially
      localises in tumour cells. An oxygen dependent photochemical reaction ensues,
      resulting in selective tumour necrosis. The effect of loss of DNA mismatch repair
      activity on the sensitivity to photodynamic therapy was tested using pairs of
      cell lines proficient or deficient in mismatch repair due to loss of either MLH1
      or MSH2 protein function. Cells were incubated with the photosensitiser
      5,10,15,20-meta-tetra(hydroxyphenyl)chlorin and exposed to laser light at 652 nm
      with various optical doses ranging from 0-1 J cm(-2). Cell survival was assessed
      using the clonogenic assay. Loss of MLH1 or MSH2 function was not associated with
      resistance to photodynamic therapy. MCF-7 cells repeatedly treated with
      photodynamic therapy expressed parental levels of MLH1, MSH2, MSH6, and PMS2. DNA
      mismatch repair-deficient and -proficient cells showed similar subcellular
      distributions of meta-tetra(hydroxyphenyl)chlorin as analysed by laser scanning
      and fluorescence microscopy. Therefore, repeated exposure of tumour cells to
      photodynamic therapy does not seem to result in loss of DNA mismatch repair, and
      loss of mismatch repair, in turn, does not seem to contribute to resistance to
      photodynamic therapy. Our results suggest recommending photodynamic therapy as a
      strategy for circumventing resistance due to loss of DNA mismatch repair.

PMID- 11953862
TI  - Role of proteolytic enzymes in human prostate bone metastasis formation: in vivo
      and in vitro studies.
AB  - Prostate cancers ability to invade and grow in bone marrow stroma is thought to
      be due in part to degradative enzymes. The formation of prostate skeletal
      metastases have been reproduced in vitro by growing co-cultures of prostatic
      epithelial cells in bone marrow stroma. Expression of urokinase plasminogen
      activator, matrix metalloproteinase 1 and 7 by prostatic epithelial cells were
      identified using immunocytochemistry. Also, in vivo tissue sections from human
      prostatic bone marrow metastases were stained. To establish the role of these
      enzymes on colony formation, inhibitory antibodies directed against urokinase
      plasminogen activator, matrix metalloproteinase 1 and matrix metalloproteinase 7
      were added into primary prostatic epithelial cells and bone marrow stroma co
      cultures. All prostatic epithelial cell cultures stained positively for matrix
      metalloproteinase 1, matrix metalloproteinase 7 and urokinase plasminogen
      activator. Generally prostatic epithelial cells derived from malignant tissues
      showed increased staining in comparison to epithelia derived from non-malignant
      tissue. In agreement with in vitro co-cultures, the in vivo tissue sections of
      prostate bone marrow metastases showed positive staining for all three enzymes.
      Inhibition studies demonstrated that blocking matrix metalloproteinase 1, matrix
      metalloproteinase 7 and urokinase plasminogen activator function reduced the
      median epithelial colony area significantly in bone marrow stroma co-cultures in
      vitro. Using a human ex-vivo model we have shown that matrix metalloproteinase 1,
      matrix metalloproteinase 7 and urokinase plasminogen activator play an important
      role in the establishment of prostatic epithelial cells within bone marrow.

PMID- 11953863
TI  - Phosphorothioate oligonucleotides, suramin and heparin inhibit DNA-dependent
      protein kinase activity.
AB  - Phosphorothioate oligonucleotides and suramin bind to heparin binding proteins
      including DNA polymerases, and inhibit their functions. In the present study, we
      report inhibition of DNA-dependent protein kinase activity by phosphorothioate
      oligonucleotides, suramin and heparin. Inhibitory effect of phosphorothioate
      oligonucleotides on DNA-dependent protein kinase activity was increased with
      length and reached a plateau at 36-mer. The base composition of phosphorothioate
      oligonucleotides did not affect the inhibitory effect. The inhibitory effect by
      phosphorothioate oligodeoxycytidine 36-mer can be about 200-fold greater than
      that by the phosphodiester oligodeoxycytidine 36-mer. The inhibitory effect was
      also observed with purified DNA-dependent protein kinase, which suggests direct
      interaction between DNA-dependent protein kinase and phosphorothioate
      oligonucleotides. DNA-dependent protein kinase will have different binding
      positions for double-stranded DNA and phosphorothioate oligodeoxycytidine 36-mer
      because they were not competitive in DNA-dependent protein kinase activation.
      Suramin and heparin inhibited DNA-dependent protein kinase activity with IC(50)
      of 1.7 microM and 0.27 microg ml(-1) respectively. DNA-dependent protein kinase
      activities and DNA double-stranded breaks repair in cultured cells were
      significantly suppressed by the treatment with suramin in vivo. Our present
      observations suggest that suramin may possibly result in sensitisation of cells
      to ionising radiation by inactivation of DNA-dependent protein kinase and the
      impairment of double-stranded breaks repair.

PMID- 11953865
TI  - ZD1839 ('Iressa'), a specific oral epidermal growth factor receptor-tyrosine
      kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft
      model.
AB  - The effect of ZD1839 ('Iressa'), a specific inhibitor of the tyrosine kinase
      activity of the epidermal growth factor receptor, on the radiation response of
      human tumour cells (LoVo colorectal carcinoma) was evaluated in vitro and in
      vivo. ZD1839 (0.5 microM, incubated days 1-5) significantly increased the anti
      proliferative effect of fractionated radiation treatment (2 Gy day(-1), days 1-3)
      on LoVo cells grown in vitro (P=0.002). ZD1839 combined with either single or
      fractionated radiotherapy in mice bearing LoVo tumour xenografts, also produced a
      highly significant increase in tumour growth inhibition (P< or = 0.001) when
      compared to treatment with either modality alone. The radio-potentiating effect
      of ZD1839 was more apparent when radiation was administered in a fractionated
      protocol. This phenomenon may be attributed to an anti proliferative effect of
      ZD1839 on tumour cell re-population between radiotherapy fractions. These data
      suggest radiotherapy with adjuvant ZD1839 could enhance treatment response.
      Clinical investigation of ZD1839 in combination with radiotherapy is therefore
      warranted.

PMID- 11953864
TI  - Inhibitor of cyclooxygenase-2 induces cell-cycle arrest in the epithelial cancer
      cell line via up-regulation of cyclin dependent kinase inhibitor p21.
AB  - Cyclooxygenase-2 is the rate-limiting enzyme in synthesis of prostaglandins and
      other eicosanoids. Prior reports have shown that inhibition of cyclooxygenase-2
      activity, either by selective inhibitors or by antisense oligonucleotide, results
      in suppression of growth of squamous cell carcinoma cell lines which express high
      cyclooxygenase-2 levels, such as NA, a cell line established from a squamous cell
      carcinoma of the tongue. To investigate the mechanisms by which cyclooxygenase-2
      inhibitors suppressed growth of these cells, the effects of NS-398, the selective
      cyclooxygenase-2 inhibitor, on cell-cycle distribution were examined. NS-398
      induced G0/G1 cell-cycle arrest in NA cells which expressed cyclooxygenase-2.
      G0/G1 arrest induced by NS-398 was accompanied by up-regulation of cyclin
      dependent kinase inhibitor p21, but not by up-regulation of the other cyclin
      dependent kinase inhibitors. Transfection with p21 antisense oligonucleotide
      inhibited cell-cycle arrest induced by NS-398. Accumulation in G0/G1 was also
      observed in NA cells transfected with cyclooxygenase-2 antisense oligonucleotide.
      On the other hand, NS-398-treated NA cells showed a loss of plasma membrane
      asymmetry, a marker of early events in apoptosis. However, NS-398 did not induce
      other morphological and biochemical changes related to apoptotic cell death.
      These results suggest that cyclooxygenase-2 inhibitor induces G0/G1 cell-cycle
      arrest in NA cells by up-regulation of p21. Our results also suggest that NS-398
      is not sufficient to complete the whole process of apoptosis in NA cells,
      although it induces an early event in apoptosis.

PMID- 11953866
TI  - Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective
      intracellular determinants of drug activity.
AB  - The combination of 5-fluorouracil-folinic acid and oxaliplatin has led to a
      significant improvement of chemotherapy efficacy in advanced pretreated
      colorectal cancer. The objective of the present study was, considering the
      oxaplatin-5-fluorouracil-folinic acid combination, to examine the impact of one
      given drug on the cellular determinants of cytotoxic activity of the other drug.
      These cellular factors were analysed on the human colon cancer cell line WiDr in
      clinically relevant conditions of drug exposure ('De Gramont' schedule) with
      oxaliplatin-folinic acid during 2 h followed by 5-fluorouracil 48 h. The DNA
      binding of oxaliplatin was significantly reduced by the presence of 5
      fluorouracil but this effect was time-dependent and after 50 h the platinum
      incorporated into DNA was identical in controls and in the drug combination. In
      the presence of oxaliplatin, there was less formation of FUH(2) which is the
      first catabolite produced in the cascade of 5-fluorouracil metabolic degradation.
      The effects of drugs on cell cycle were quite different from one drug to the
      other with oxaliplatin inducing a shift towards G(2) accumulation and 5
      fluorouracil-folinic acid to a greater proportion of cells in G(1)-S. When
      oxaliplatin and 5-fluorouracil-folinic acid were combined the cell cycle effects
      were very similar to that of the 5-fluorouracil-folinic acid sequence alone.
      Oxaliplatin was able to reduce thymidylate synthase activity with a marked impact
      28 h after the beginning of cell exposure to the drug. The 5-fluorouracil-folinic
      acid drug sequence led to a profound reduction in thymidylate synthase activity
      and this decrease was not markedly enhanced by the presence of oxaliplatin.
      Regarding apoptosis, changes in mitochondrial membrane permeability were observed
      in the presence of the tested drugs and the impact of 5-fluorouracil-folinic acid
      was greater than that of oxaliplatin. The addition of oxaliplatin did not amplify
      the action of 5-fluorouracil-folinic acid upon mitochondrial membrane
      permeability change. The presence of oxaliplatin itself did not modify the
      intracellular concentration of total reduced folates. The fact that oxaliplatin
      may reduce 5-fluorouracil catabolism could be central in explaining the supra
      additive interaction between these drugs.

PMID- 11953867
TI  - Laminin gamma 1 chain peptide, C-16 (KAFDITYVRLKF), promotes migration, MMP-9
      secretion, and pulmonary metastasis of B16-F10 mouse melanoma cells.
AB  - Laminin-1, a heterotrimer of alpha 1, beta 1, and gamma 1 chains specific to
      basement membrane, promotes cell adhesion and migration, proteinase secretion and
      metastases of tumour cells. Several active sites on the alpha 1 chain have been
      found to promote B16-F10 melanoma lung colonisation and here we have determined
      whether additional tumour promoting sites exist on the beta 1 and gamma 1 chains.
      Recently, we have identified novel cell adhesive peptides derived from laminin
      beta 1 and gamma 1 chains by systematic screening of synthetic peptides. Nine
      beta 1 peptides and seven gamma 1 peptides active for cell adhesion were tested
      for their effects on experimental pulmonary metastases of B16-F10 mouse melanoma
      cells in vivo. The most active adhesive peptide derived from the gamma 1 chain
      globular domain, C-16 (KAFDITYVRLKF), significantly enhanced pulmonary metastases
      of B16-F10 cells, whereas no other peptides showed enhancement. C-16 also
      stimulated migration of B16-F10 cells in the Boyden chamber assay in vitro.
      Furthermore, C-16 significantly induced the production of MMP-9 from B16-F10
      cells. These results suggest that this specific laminin gamma 1 chain peptide has
      a metastasis-promoting activity and might be a new molecular target of anti
      cancer treatment.

PMID- 11953868
TI  - Isolated limb perfusion with actinomycin D and TNF-alpha results in improved
      tumour response in soft-tissue sarcoma-bearing rats but is accompanied by severe
      local toxicity.
AB  - Previously we demonstrated that addition of Tumour Necrosis Factor-alpha to
      melphalan or doxorubicin in a so-called isolated limb perfusion results in
      synergistic antitumour responses of sarcomas in both animal models and patients.
      Yet, 20 to 30% of the treated tumours do not respond. Therefore agents that
      synergise with tumour necrosis factor alpha must be investigated. Actinomycin D
      is used in combination with melphalan in isolated limb perfusion in the treatment
      of patients with melanoma in-transit metastases and is well known to augment
      tumour cell sensitivity towards tumour necrosis factor alpha in vitro. Both
      agents are very toxic, which limits their systemic use. Their applicability may
      therefore be tested in the isolated limb perfusion setting, by which the tumours
      can be exposed to high concentrations in the absence of systemic exposure. To
      study the beneficial effect of the combination in vivo, BN-175 soft tissue
      sarcoma-bearing rats were perfused with various concentrations of actinomycin D
      and tumour necrosis factor alpha. When used alone the drugs had only little
      effect on the tumour. Only when actinomycin D and tumour necrosis factor alpha
      were combined a tumour response was achieved. However, these responses were
      accompanied by severe, dose limiting, local toxicity such as destruction of the
      muscle tissue and massive oedema. Our results show that isolated limb perfusion
      with actinomycin D in combination with tumour necrosis factor alpha leads to a
      synergistic anti-tumour response but also to idiosyncratic locoregional toxicity
      to the normal tissues. Actinomycin D, in combination with tumour necrosis factor
      alpha, should not be explored in the clinical setting because of this. The
      standard approach in the clinic remains isolated limb perfusion with tumour
      necrosis factor alpha in combination with melphalan.

PMID- 11953869
TI  - Detection of polyol accumulation in a new ovarian carcinoma cell line, CABA I:
      a(1)H NMR study.
AB  - Ovarian carcinomas represent a major form of gynaecological malignancies, whose
      treatment consists mainly of surgery and chemotherapy. Besides the difficulty of
      prognosis, therapy of ovarian carcinomas has reached scarce improvement, as a
      consequence of lack of efficacy and development of drug-resistance. The need of
      different biochemical and functional parameters has grown, in order to obtain a
      larger view on processes of biological and clinical significance. In this paper
      we report novel metabolic features detected in a series of different human ovary
      carcinoma lines, by (1)H NMR spectroscopy of intact cells and their extracts.
      Most importantly, a new ovarian adenocarcinoma line CABA I, showed strong signals
      in the spectral region between 3.5 and 4.0 p.p.m., assigned for the first time to
      the polyol sorbitol (39+/-11 nmol/10(6) cells). (13)C NMR analyses of these cells
      incubated with [1-(13)C]-D-glucose demonstrated labelled-sorbitol formation. The
      other ovarian carcinoma cell lines (OVCAR-3, IGROV 1, SK-OV-3 and OVCA432),
      showed, in the same spectral region, intense resonances from other metabolites:
      glutathione (up to 30 nmol/10(6) cells) and myo-inositol (up to 50 nmol/10(6)
      cells). Biochemical and biological functions are suggested for these compounds in
      human ovarian carcinoma cells, especially in relation to their possible role in
      cell detoxification mechanisms during tumour progression.

PMID- 11953870
TI  - Mechanisms of nordihydroguaiaretic acid-induced growth inhibition and apoptosis
      in human cancer cells.
AB  - Lipoxygenase metabolites of arachidonic acid can act as growth promoting factors
      for various cancer cell lines. Here we demonstrate that the 5-lipoxygenase
      inhibitor nordihydroguaiaretic acid potently inhibits anchorage-independent
      growth of human pancreatic and cervical cancer cells in soft agar and delays
      growth of pancreatic and cervical tumours established in athymic mice.
      Furthermore, nordihydroguaiaretic acid induces apoptosis of these cancer cells in
      vitro and in vivo. Potential mechanisms mediating these effects of
      nordihydroguaiaretic acid were examined. Nordihydroguaiaretic acid had no
      inhibitory effect on growth and survival signals such as tyrosine phosphorylation
      of the epidermal growth factor receptor or basal and growth factor-stimulated
      activities of extracellular signal-regulated kinase 1/2, p70(s6k) and AKT but
      selectively inhibited expression of cyclin D1 in the cancer cells. In addition,
      treatment with nordihydroguaiaretic acid lead to a disruption of the filamentous
      actin cytoskeleton in human pancreatic and cervical cancer cells which was
      accompanied by the activation of Jun-NH(2)-terminal kinase and p38(mapk). Similar
      effects were obtained by treatment of the cancer cells with cytochalasin D. These
      results suggest that nordihydroguaiaretic acid induces anoikis-like apoptosis as
      a result of disruption of the actin cytoskeleton in association with the
      activation of stress activated protein kinases. In conclusion,
      nordihydroguaiaretic acid could constitute a lead compound in the development of
      novel therapeutic agents for various types of cancer.

PMID- 11953873
TI  - Getting the right dose in cancer chemotherapy--time to stop using surface area?

PMID- 11953871
TI  - 213Bi-PAI2 conjugate selectively induces apoptosis in PC3 metastatic prostate
      cancer cell line and shows anti-cancer activity in a xenograft animal model.
AB  - A novel alpha-particle emitting ((213)Bi) plasminogen activator inhibitor type 2
      construct, which targets the membrane-bound urokinase plasminogen activator on
      prostate cancer cells, was prepared and evaluated in vitro and in a xenograft
      animal model. The PC3 prostate cancer cell line expresses urokinase plasminogen
      activator which binds to its receptor on the cell membrane; plasminogen activator
      inhibitor type 2 is bound to urokinase plasminogen activator/urokinase
      plasminogen activator receptor to form stable complexes. In vitro, the
      cytotoxicity of (213)Bi-plasminogen activator inhibitor type 2 against prostate
      cancer cells was tested using the MTS assay and apoptosis was documented using
      terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end
      labelling (TUNEL) assay. In vivo, antiproliferative effects for tumours and
      prostate cancer lymph node metastasis were carried out in an athymic nude mouse
      model with a subcutaneous xenograft of PC3 cells. (213)Bi-plasminogen activator
      inhibitor type 2 was specifically cytotoxic to PC3 cells in a concentration
      dependent fashion, causing the cells to undergo apoptosis. A single local or i.p.
      injection of (213)Bi-plasminogen activator inhibitor type 2 was able to
      completely regress the growth of tumours and lymph node metastases 2 days post
      subcutaneous inoculation, and obvious tumour regression was achieved in the
      therapy groups compared with control groups with (213)Bi-plasminogen activator
      inhibitor type 2 when the tumours measured 30-40 mm(3) and 85-100 mm(3). All
      control animals and one of five (20%) mice treated with 3 mCi kg(-1) (213)Bi
      plasminogen activator inhibitor type 2 developed metastases in the lymph nodes
      while no lymphatic spread of cancer was found in the 6 mCi kg(-1) treated groups
      at 2 days and 2 weeks post-cell inoculation. These results demonstrate that this
      novel (213)Bi-plasminogen activator inhibitor type 2 conjugate selectively
      targets prostate cancer in vitro and in vivo, and could be considered for further
      development for the therapy of prostate cancer, especially for the control of
      micro-metastases or in minimal residual disease.

PMID- 11953875
TI  - Serum CEA and CA 15-3 as prognostic factors in primary breast cancer.
AB  - In the present study, we investigated the association of the serum levels of the
      tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free
      survival and death from disease in 1046 women with breast cancer without
      metastases at the time of primary diagnosis in relation to age and the
      established prognostic factors tumour size, lymph node status, histological
      grading and hormone receptor status. We found that elevated pre-operative serum
      marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003)
      and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001
      both) in univariate analyses. By comparing pre- and post-operative values we
      found a decline in values post-surgery. In those patients where marker levels of
      carcinoembryonic antigen decreased more than 33%, a significantly higher risk for
      relapse and death from disease (both P=0.0001) in univariate analyses was
      observed. In multivariate analysis this decrease of carcinoembryonic antigen
      proved to be an independent prognostic factor. The results for cancer antigen 15
      3 were comparable to carcinoembryonic antigen in univariate analyses but showed
      no significance in multivariate analysis. In this study the post-operative
      decrease of the serum tumour marker carcinoembryonic antigen was a strong
      independent prognostic factor for disease free survival and death from disease in
      breast cancer patients.

PMID- 11953874
TI  - Predictive testing for BRCA1/2: attributes, risk perception and management in a
      multi-centre clinical cohort.
AB  - The aim of this multi-centre UK study is to examine the attributes of a cohort
      offered predictive genetic testing for breast/ovarian cancer predisposition.
      Participants are adults unaffected with cancer from families with a known BRCA1/2
      mutation. This is the first large multi-centre study of this population in the
      UK. The study evaluates mental health, perceived risk of developing cancer,
      preferred risk management options, and motivation for genetic testing.
      Participants were assessed when coming forward for genetic counselling prior to
      proceeding to genetic testing. Three hundred and twelve individuals, 76% of whom
      are female, from nine UK centres participated in the study. There are no gender
      differences in rates of psychiatric morbidity. Younger women (<50 years) are more
      worried about developing cancer than older women. Few women provide accurate
      figures for the population risk of breast (37%) or ovarian (6%) cancer but most
      think that they are at higher risk of developing breast (88%) and ovarian (69%)
      cancer than the average woman. Cancer related worry is not associated with
      perceived risk or uptake of risk management options except breast self
      examination. The findings indicate that younger women may be particularly
      vulnerable at the time of the offer of a predictive genetic test.

PMID- 11953877
TI  - A phase II study of active specific immunotherapy and 5-FU/Leucovorin as adjuvant
      therapy for stage III colon carcinoma.
AB  - Active specific immunotherapy, using vaccines with autologous tumour cells and
      BCG, significantly reduces the rate of tumour recurrence in stage II colon cancer
      patients, while no clinical benefit has yet been observed in stage III patients.
      Adjuvant treatment with 5-Fluorouracil/Leucovorin is now considered standard
      therapy for stage III colon carcinoma and results in an absolute survival benefit
      of approximately 10%. Yet, the 5-year overall survival rate of stage III colon
      cancer patients is only 40-50%. Combining chemotherapy and immunotherapy might
      improve prognosis for stage III patients, especially when considering that active
      specific immunotherapy and chemotherapy have shown synergistic effects in pre
      clinical tumour models. We performed a phase II study with 56 patients, using the
      combination of active specific immunotherapy and chemotherapy as an adjuvant
      therapy in stage III colon cancer patients to assess the influence of 5
      Fluorouracil/Leucovorin on anti-tumour immunity induced by autologous tumour cell
      vaccinations. Anti-tumour immunity was measured before and after chemotherapy by
      means of delayed type hypersensitivity reactions, taken 48 h after the third and
      the fourth vaccination. We also investigated the toxicity of this combined immuno
      chemotherapy treatment. Delayed type hypersensitivity reactions before
      chemotherapy had a median size of 20.3 mm, while after chemotherapy delayed type
      hypersensitivity size was 18.4 mm (P=0.01), indicating that chemotherapy hardly
      affected anti-tumour immunity. The severity of ulcers at the BCG vaccination
      sites was comparable to previous studies. In 30% of the patients grade III or
      grade IV chemotherapy related toxicity was seen; this is comparable to what is
      normally observed after adjuvant chemotherapy alone. This study shows that the
      active specific immunotherapy-induced anti-tumour immune response is only
      minimally impaired by consecutive chemotherapy and that the combined treatment of
      stage III colon cancer patients with active specific immunotherapy and 5
      Fluorouracil/Leucovorin does not cause unexpected toxicity.

PMID- 11953876
TI  - The pattern of recurrence of adenocarcinoma of the oesophago-gastric junction.
AB  - Knowledge of the pattern of recurrence of surgically treated cases of
      adenocarcinoma of the oesophago-gastric junction is important both for better
      understanding of their biological nature and for future strategic planning of
      therapy. The aim of this study is to demonstrate and compare the pattern of
      dissemination and recurrence in patients with Type I and Type II adenocarcinoma
      of oesophago-gastric junction. A prospective audit of the clinico-pathological
      features of patients who had undergone surgery with curative intent for
      adenocarcinoma of oesophago-gastric junction between 1991 and 1996 was
      undertaken. Patients were followed up by regular clinical examination. Clinical
      evaluation was supported by ultrasound, computerised tomography, radio-isotope
      bone scan, endoscopy and laparotomy each with biopsy and histology where
      appropriate. One hundred and sixty-nine patients with oesophago-gastric junction
      tumours (94 Type I and 75 Type II) have been followed up for a median of 75.3 (57
      133) months. One hundred and three patients developed proven recurrent disease.
      The median time to recurrence was 23.3 (14.2-32.4) months for Type I and 20.5
      (11.6-29.4) for Type II cancers. The most frequent type of recurrence was
      haematogenous (56% of Type I recurrences and 54% of Type II) of which 56% were
      detected within 1 year of surgery. The most frequent sites were to liver (27%),
      bone (18%) brain (11%) and lung (11%). Local recurrence occurred in 33% of Type I
      cancer and 29% of Type II recurrences. Nodal recurrence occurred in 18 and 25% of
      Type I and Type II cancer recurrences, most frequently to coeliac or porta
      hepatis nodes (64%). Only 7% of Type I and 15% of Type II cancer recurrences were
      by peritoneal dissemination. Type I and Type II adenocarcinoma of the oesophago
      gastric junction have a predominantly early, haematogenous pattern of recurrence.
      There is a need to better identify the group of patients with small metastases at
      the time of diagnosis who are destined to develop recurrent disease in order that
      they may be spared surgery and those with micro metastases in order that they can
      be offered multi-modality therapy including early post operative or neo-adjuvant
      chemotherapy.

PMID- 11953878
TI  - Is there a dose response relationship for clodronate in the treatment of tumour
      induced hypercalcaemia?
AB  - Eighty-six patients with tumour induced hypercalcaemia were randomised to 600,
      900, 1200 or 1500 mg of intravenous clodronate, according to post hydration serum
      calcium levels. Sixty-seven were evaluable for response. The overall response
      rate was 49.3% (95% CI: 36.8-61.8) with no significant difference in response
      rates, i.e. achievement of normocalcaemia at days 6-9 (corrected serum calcium <
      or =2.6 mmol l(-1)) across all groups.

PMID- 11953879
TI  - A phase II study of mitomycin C, cisplatin and continuous infusion 5-fluorouracil
      (MCF) in the treatment of patients with carcinoma of unknown primary site.
AB  - Carcinoma of unknown primary site remains a common clinical diagnosis, accounting
      for between 5 and 10% of all cancer patients. Numerous combination chemotherapy
      regimens have been used in the management of carcinoma of unknown primary site,
      resulting in response rates of 0-48%. We present the results of a single centre
      phase II study of the use of the combination of mitomycin C (7 mg m(-2) on day 1
      of cycles 1, 3 and 5) cisplatin (60 mg m(-2) on day 1) and continuous infusion 5
      fluorouracil (300 mg m(-2) daily), MCF, delivered as a 21-day cycle, in patients
      with carcinoma of unknown primary site. Thirty-one patients with a diagnosis of
      carcinoma of unknown primary site were treated in Aberdeen Royal Infirmary
      between 1997 and 2001 with MCF. In total, 136 cycles of MCF were delivered
      (median of 5 cycles per patient). Toxicity was acceptable, with 19% grade 3 or 4
      neutropenia, 16% grade 3 or 4 thrombocytopenia and 13% grade 3 or 4 nausea and
      vomiting. No cases of neutropenic sepsis were seen and there were no treatment
      related deaths, however, six patients developed thrombotic complications. The
      overall response rate was 27% (CR 3%; PR 23%). Median time to progression was 3.4
      months (95% CI 1.1-5.6 months) and median overall survival was 7.7 months (95% CI
      5.7-9.8 months). Survival at 1 year was 28%, and at 2 years, 10%. MCF is a
      tolerable regimen with comparable toxicity, response rates and survival data to
      most platinum-based combination chemotherapy regimens in use for this devastating
      disease.

PMID- 11953880
TI  - The level of haemoglobin in anaemic cancer patients correlates positively with
      quality of life.
AB  - The aim of this study was to assess the relationship between haemoglobin level
      and quality-of-life in anaemic cancer patients. Patients, diagnosed with one of
      four cancers, were recruited if their haemoglobin level was <12 g dl(-1) (female)
      or <13 g dl(-1) (male). The condition-specific Functional Assessment of Cancer
      Therapy-Anaemia and the generic SF-36 were used to assess quality-of-life. Thirty
      six per cent of the 179 recruited patients had breast cancer, 28% ovarian cancer,
      25% lung cancer, and 11% multiple myeloma. Their mean (s.d.) haemoglobin level
      was 10.66 (1.04) g dl(-1). Partial correlations controlling for the potentially
      confounding effects of age, gender, and time since diagnosis found significant
      positive relationships between haemoglobin and all domains of the Functional
      Assessment of Cancer Therapy-Anaemia, and with all but two of the SF-36 domains.
      On linear regression controlling for the same factors, each unit haemoglobin rise
      equalled an average 8.19 Functional Assessment of Cancer Therapy-Anaemia, and an
      average 6.88 Functional Assessment of Cancer Therapy-Fatigue, increase.
      Haemoglobin accounted for a similar amount of variability (8%) in SF-36 scores.
      In conclusion, quality-of-life has been found to be significantly positively
      related to haemoglobin level in anaemic cancer patients. This suggests that
      normalisation of haemoglobin in cancer patients is likely to increase their
      quality-of-life. The greater sensitivity of the condition-specific Functional
      Assessment of Cancer Therapy-Anaemia compared with the generic SF-36 suggests
      that the Functional Assessment of Cancer Therapy-Anaemia can be used alone to
      assess quality-of life in this patient group.

PMID- 11953882
TI  - Cimetidine modulates the antigen presenting capacity of dendritic cells from
      colorectal cancer patients.
AB  - Cimetidine, a H(2) receptor antagonist, has been reported to improve survival in
      gastrointestinal cancer patients. These effects have largely been attributed to
      the enhancing effects of cimetidine on the host's antitumour cell-mediated immune
      response, such as inhibition of suppressor T lymphocyte activity, stimulation of
      natural killer cell activity and increase of interleukin-2 production from helper
      T lymphocytes. We conducted an in vitro study on the effects of cimetidine on
      differentiation and antigen presenting capacity of monocyte-derived dendritic
      cells from advanced colorectal cancer patients and normal controls. As a result,
      an investigation of expression of surface molecules associated with dendritic
      cells by flow cytometric analyses showed that cimetidine had no enhancing effect
      on differentiation of dendritic cells from cancer patients and normal controls.
      An investigation of [(3)H]thymidine incorporation by allogeneic mixed lymphocyte
      reactions revealed that cimetidine increased the antigen presenting capacity of
      dendritic cells from both materials. Moreover, a higher antigen presenting
      capacity was observed in advanced cancer patients compared to normal controls.
      These effects might be mediated via specific action of cimetidine and not via
      H(2) receptors because famotidine did not show similar effects. Our results
      suggest that cimetidine may enhance the host's antitumour cell-mediated immunity
      by improving the suppressed dendritic cells function of advanced cancer patients.

PMID- 11953881
TI  - CXCR4/CXCL12 expression and signalling in kidney cancer.
AB  - CXCL12 (SDF-1), a CXC-chemokine, and its specific receptor, CXCR4, have recently
      been shown to be involved in tumourgenesis, proliferation and angiogenesis.
      Therefore, we analysed CXCL12alpha/CXCR4 expression and function in four human
      kidney cancer cell lines (A-498, CAKI-1, CAKI-2, HA-7), 10 freshly harvested
      human tumour samples and corresponding normal kidney tissue. While none of the
      analysed tumour cell lines expressed CXCL12alpha, A-498 cells were found to
      express CXCR4. More importantly, real-time RT-PCR analysis of 10 tumour samples
      and respective adjacent normal kidney tissue disclosed a distinct and divergent
      downregulation of CXCL12alpha and upregulation of CXCR4 in primary tumour tissue.
      To prove that the CXCR4 protein is functionally active, rhCXCL12alpha was
      investigated for its ability to induce changes of intracellular calcium levels in
      A-498 cells. Moreover, we used cDNA expression arrays to evaluate the biological
      influence of CXCL12alpha. Comparing gene expression profiles in rhCXCL12alpha
      stimulated vs unstimulated A-498 kidney cancer cells revealed specific regulation
      of 31 out of 1176 genes tested on a selected human cancer array, with a prominent
      stimulation of genes involved in cell-cycle regulation and apoptosis. The genetic
      changes reported here should provide new insights into the developmental paths
      leading to tumour progression and may also aid the design of new approaches to
      therapeutic intervention.

PMID- 11953884
TI  - Heparanase expression is a prognostic indicator for postoperative survival in
      pancreatic adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma has a median survival of less than 6 months from
      diagnosis. This is due to the difficulty in early diagnosis, the aggressive
      biological behaviour of the tumour and a lack of effective therapies for advanced
      disease. Mammalian heparanase is a heparan-sulphate proteoglycan cleaving enzyme.
      It helps to degrade the extracellular matrix and basement membranes and is
      involved in angiogenesis. Degradation of extracellular matrix and basement
      membranes as well as angiogenesis are key conditions for tumour cell spreading.
      Therefore, we have analysed the expression of heparanase in human pancreatic
      cancer tissue and cell lines. Heparanase is expressed in cell lines derived from
      primary tumours as well as from metastatic sites. By immunohistochemical
      analysis, it is preferentially expressed at the invading edge of a tumour at both
      metastatic and primary tumour sites. There is a trend towards heparanase
      expression in metastasising tumours as compared to locally growing tumours.
      Postoperative survival correlates inversely with heparanase expression of the
      tumour reflected by a median survival of 34 and 17 month for heparanase negative
      and positive tumours, respectively. Our results suggest, that heparanase promotes
      cancer cell invasion in pancreatic carcinoma and could be used as a prognostic
      indicator for postoperative survival of patients.

PMID- 11953883
TI  - Molecular changes in the expression of human colonic nutrient transporters during
      the transition from normality to malignancy.
AB  - Healthy colonocytes derive 60-70% of their energy supply from short-chain fatty
      acids, particularly butyrate. Butyrate has profound effects on differentiation,
      proliferation and apoptosis of colonic epithelial cells by regulating expression
      of various genes associated with these processes. We have previously shown that
      butyrate is transported across the luminal membrane of the colonic epithelium via
      a monocarboxylate transporter, MCT1. In this paper, using immunohistochemistry
      and in situ hybridisation histochemistry, we have determined the profile of MCT1
      protein and mRNA expression along the crypt to surface axis of healthy human
      colonic tissue. There is a gradient of MCT1 protein expression in the apical
      membrane of the cells along the crypt-surface axis rising to a peak in the
      surface epithelial cells. MCT1 mRNA is expressed along the crypt-surface axis and
      is most abundant in cells lining the crypt. Analysis of healthy colonic tissues
      and carcinomas using immunohistochemistry and Western blotting revealed a
      significant decline in the expression of MCT1 protein during transition from
      normality to malignancy. This was reflected in a corresponding reduction in MCT1
      mRNA expression, as measured by Northern analysis. Carcinoma samples displaying
      reduced levels of MCT1 were found to express the high affinity glucose
      transporter, GLUT1, suggesting that there is a switch from butyrate to glucose as
      an energy source in colonic epithelia during transition to malignancy. The
      expression levels of MCT1 in association with GLUT1 could potentially be used as
      determinants of the malignant state of colonic tissue.

PMID- 11953885
TI  - The hypoxia-inducible genes VEGF and CA9 are differentially regulated in
      superficial vs invasive bladder cancer.
AB  - Regulation by hypoxia may underlie the expression of vascular endothelial growth
      factor in bladder cancer. We have compared the distribution of vascular
      endothelial growth factor mRNA with a hypoxia marker, carbonic anhydrase 9 (CA
      IX). vascular endothelial growth factor mRNA was analysed by in situ
      hybridisation and CA IX by immunochemistry in 22 cases of bladder cancer. The
      relationship of microvessels to the distribution of CA IX was determined. In a
      separate series of 49 superficial tumours, CA IX immunostaining was compared with
      clinico-pathological outcome. In superficial and invasive disease there was
      overlap in the expression of vascular endothelial growth factor and CA IX, CA IX
      being more widespread. Both were expressed predominantly on the luminal surface,
      and surrounding areas of necrosis (invasive tumours). Expression of both factors
      was greater in superficial disease. Expression was absent within approximately 80
      microm of microvessels. Unlike vascular endothelial growth factor, CA IX did not
      predict outcome in superficial disease. Differential responses to reoxygenation
      provide one explanation: vascular endothelial growth factor mRNA declined
      rapidly, while CA IX expression was sustained for >72 h. Expression of vascular
      endothelial growth factor mRNA in bladder tumours is consistent with hypoxic
      regulation and suggests differential regulation in superficial vs invasive
      disease. The expression of CA IX on the luminal surface justifies investigation
      of its utility as a therapeutic target/prognostic indicator.

PMID- 11953886
TI  - Gene expression profiles of bladder cancers: evidence for a striking effect of in
      vitro cell models on gene patterns.
AB  - In order to assess the effect of in vitro models on the expression of key genes
      known to be implicated in the development or progression of cancer, we quantified
      by real-time quantitative PCR the expression of 28 key genes in three bladder
      cancer tissue specimens and in their derived cell lines, studied either as one
      dimensional single cell suspensions, two-dimensional monolayers or three
      dimensional spheroids. Global analysis of gene expression profiles showed that in
      vitro models had a dramatic impact upon gene expression. Remarkably, quantitative
      differences in gene expression of 2-63-fold were observed in 24 out of 28 genes
      among the cell models. In addition, we observed that the in vitro model which
      most closely mimicked in vivo mRNA phenotype varied with both the gene and the
      patient. These results provide evidence that mRNA expression databases based on
      cancer cell lines, which are studied to provide a rationale for selection of
      therapy on the basis of molecular characteristics of a patient's tumour, must be
      carefully interpreted.

PMID- 11953887
TI  - Cirrhotic livers reveal genetic changes in the MDM2-P14ARF system of cell cycle
      regulators.
AB  - The genesis of hepatocellular carcinoma is promoted by changes in the regulatory
      MDM2-P14ARF system. The incidence of such changes has to date not been analysed
      in non-tumourous livers showing regenerative proliferation. In the present study,
      24 cirrhotic livers of alcohol-, autoimmue disorder- or HCV-caused genesis were
      screened for MDM2-P14ARF alterations at the level of protein, DNA and mRNA. Using
      confocal laser scanning microscopy, the absence of MDM2 and P14ARF expression was
      detected in all samples except three HCV-infected livers (four livers) which
      contained hepatocytes overexpressing MDM2 (P14ARF) protein. In two of the samples
      lacking P14ARF expression, laser microdissection and PCR demonstrated deletion of
      the P14ARF gene. The P14ARF gene amplified from other specimens did not carry
      mutations. MDM2 splicing variants were present in tissues from alcohol- and
      autoimmune disorder-induced cirrhoses. Sequencing of full-size mRNA revealed a
      MDM2 mis-sense mutation in an alcohol-induced cirrhosis. One sample contained
      regenerative nodules with genetic instability occurring at MDM2 locus D12S83
      according to the data of automatic PCR fragment analysis. In summary, this study
      gives first evidence for different types of MDM2 and P14ARF alterations in
      cirrhotic livers. We suggest that the changes impair the regulatory MDM2-P14ARF
      system, thus possibly favouring regenerative proliferation and transformation.

PMID- 11953888
TI  - How to calculate the dose of chemotherapy.
AB  - Body surface area-dosing does not account for the complex processes of cytotoxic
      drug elimination. This leads to an unpredictable variation in effect. Overdosing
      is easily recognised but it is possible that unrecognised underdosing is more
      common and may occur in 30% or more of patients receiving standard regimen. Those
      patients who are inadvertently underdosed are at risk of a significantly reduced
      anticancer effect. Using published data, it can be calculated that there is an
      almost 20% relative reduction in survival for women receiving adjuvant
      chemotherapy for breast cancer as a result of unrecognised underdosing.
      Similarly, the cure rate of cisplatin-based chemotherapy for advanced testicular
      cancer may be reduced by as much as 10%. The inaccuracy of body surface area
      dosing is more than an inconvenience and it is important that methods for more
      accurate dose calculation are determined, based on the known drug elimination
      processes for cytotoxic chemotherapy. Twelve rules for dose calculation of
      chemotherapy are given that can be used as a guideline until better dose
      calculation methods become available. Consideration should be given to using
      fixed dose guidelines independent of body surface area and based on drug
      elimination capability, both as a starting dose and for dose adjustment, which
      may have accuracy, safety and financial advantages.

PMID- 11953889
TI  - Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome
      proliferator-activated receptor-gamma.
AB  - A rare immunohistochemical study using 28 surgical sections of human
      chondrosarcoma revealed that 67.9% of tumour cells had weak (10-40%) or strong
      (>40%) positive immunoreaction for peroxisome proliferator-activated receptor
      gamma. The expression of peroxisome proliferator-activated receptor-gamma mRNA
      and protein in human chondrosarcoma cell line OUMS-27 was also determined by
      reverse transcription-polymerase chain reaction and immunocytochemistry,
      respectively. Furthermore, the effects of peroxisome proliferator-activated
      receptor-gamma ligands on cell proliferation and survival were investigated in
      OUMS-27 cells. Pioglitazone, a selective ligand for peroxisome proliferator
      activated receptor-gamma, and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d
      PGJ(2)), a putative endogenous ligand for peroxisome proliferator-activated
      receptor-gamma, inhibited the proliferation of OUMS-27 cells in a dose-dependent
      manner. The mechanism of cytotoxic effects of 15d-PGJ(2) was via apoptosis as
      shown by DNA fragmentation using TUNEL stain and DNA ladder formation, and by
      ultrastructural analysis using transmission electron microscopy. Flow-cytometric
      analysis using annexin-V-fluorescein and propidium iodide detected the early
      change of apoptosis, as well as necrosis of OUMS-27 cells at 4 h after co
      incubation with 15d-PGJ(2). These results suggest that peroxisome proliferator
      activated receptor-gamma may play a significant role in the pathogenesis of
      chondrosarcoma, and peroxisome proliferator-activated receptor-gamma ligands,
      especially 15d-PGJ(2), may be of therapeutic value in the treatment of human
      chondrosarcoma.

PMID- 11953891
TI  - Modulation of colony stimulating factor release and apoptosis in human colon
      cancer cells by anticancer drugs.
AB  - Modulation of the immune response against tumour cells is emerging as a valuable
      approach for cancer treatment. Some experimental studies have shown that
      secretion of colony stimulating factors by cancer cells reduces their
      tumorigenicity and increases their immunogenicity probably by promoting the
      cytolitic and antigen presenting activities of leukocytes. We have observed that
      human colon cancer cells (HT-29) are able to secrete granulocyte-macrophage
      colony stimulating factor, granulocyte-colony stimulating factor and macrophage
      colony stimulating factor when stimulated with cytokines (IL-1beta and TNF
      alpha). In this study we assessed, for the first time, the effects of several
      anticancer drugs on colony stimulating factor release or apoptosis in HT-29
      cells. Cytokine-induced release of granulocyte-macrophage-colony stimulating
      factor, granulocyte-colony stimulating factor and macrophage-colony stimulating
      factor was significantly increased by cisplatin and 6-mercaptopurine. Taxol only
      increased macrophage-colony stimulating factor release while reduced that of
      granulocyte-colony stimulating factor. No changes in colony stimulating factor
      secretion were observed after treatment with methotrexate. Only cisplatin and
      taxol induced apoptosis in these cells. Secretion of colony stimulating factors
      by colon cancer cells may contribute to the immune host response against them.
      Anticancer drugs such as cisplatin and 6-mercaptopurine increase colony
      stimulating factor secretion by cytokine stimulated cancer cells probably through
      mechanisms different to those leading to cell apoptosis, an effect that may
      contribute to their anti-neoplasic action.

PMID- 11953890
TI  - Nitric oxide of human colorectal adenocarcinoma cell lines promotes tumour cell
      invasion.
AB  - The present study investigates the role of nitric oxide and the involvement of
      nitric oxide synthase II isoform on the invasion of human colorectal
      adenocarcinoma cell lines HRT-18 and HT-29. HRT-18 cells, which constitutively
      express nitric oxide synthase II mRNA were three-fold more invasive in a Matrigel
      invasion assay than nitric oxide synthase II mRNA negative HT-29 cells. Treatment
      of HT-29 cells with the nitric oxide donor Deta NONOate (50 nM) as well as
      induction of nitric oxide synthase II mRNA and production of endogenous nitric
      oxide by inflammatory cytokines (IFN-gamma and IL-1alpha) increased the
      invasiveness of HT-29 cells by approximately 40% and 75%, respectively. In HT-29
      cells nitric oxide synthase II mRNA was also induced in co-culture with human
      monocytes. The invasiveness of HRT-18 cells and stimulated HT-29 cells was partly
      inhibited by the nitric oxide synthase II inhibitor 1400 W. These results show
      that nitric oxide increases the invasion of human colorectal adenocarcinoma cell
      lines HRT-18 and HT-29, and the involvement of nitric oxide synthase II isoform
      in tumour cell invasion. Therefore, the production of nitric oxide and secretion
      of pro-inflammatory cytokines by tumour-associated macrophages, which in turn
      induce nitric oxide synthase II isoform in tumour cells, promotes tumour cell
      invasiveness.

PMID- 11953892
TI  - Effective treatment of experimental U-87MG human glioblastoma in nude mice with a
      targeted cytotoxic bombesin analogue, AN-215.
AB  - Some brain tumours, such as glioblastomas express high levels of receptors for
      bombesin/gastrin releasing peptide. We investigated whether bombesin/gastrin
      releasing peptide receptors found in glioblastoma cell lines can be utilised for
      targeting of a cytotoxic bombesin analogue, AN-215 consisting of a potent
      derivative of doxorubicin, 2-pyrrolino-doxorubicin (AN-201) linked to a bombesin
      like peptide carrier. This study reports the effect of AN-215 on the growth of U
      87MG human glioblastomas xenografted into nude mice. High affinity binding of AN
      215 to U-87MG tumours was characterised by an IC(50) value of 4.0+/-0.1 nM, as
      determined by radioreceptor assays. mRNA analyses revealed the presence of mRNA
      for BN receptor subtypes 1 and 2. Treatment with AN-215 significantly (P<0.05)
      extended tumour doubling time from 4.54+/-0.2 days to 8.18+/-1.8 days and
      inhibited tumour growth as demonstrated by a 69.6% reduction in final tumour
      volume (P<0.001) and a 64.6% decrease in tumour weight as compared to controls.
      Cytotoxic radical AN-201 at the same dose was ineffective. The antitumour effect
      of AN-215 could be blocked by pretreatment with an excess of a bombesin
      antagonist, indicating that the action of this cytotoxic analogue is receptor
      mediated. Our results suggest that patients with inoperable brain tumours such as
      malignant gliomas may benefit from targeted chemotherapy based on cytotoxic
      bombesin analogue AN-215.

PMID- 11953893
TI  - Antisense epidermal growth factor receptor RNA transfection in human glioblastoma
      cells down-regulates telomerase activity and telomere length.
AB  - Epidermal growth factor receptor is overexpressed and/or amplified in up to 50%
      of glioblastomas, suggesting an important role of this gene in glial
      tumorigenesis and progression. In the present study we demonstrated that
      epidermal growth factor receptor is involved in regulation of telomerase activity
      in glioblastoma. Antisense-epidermal growth factor receptor approach was used to
      inhibit epidermal growth factor receptor expression of glioblastoma U87MG cells.
      Telomerase activity in antisense-epidermal growth factor receptor cells decreased
      by up to 54 folds compared with control cells. Moreover, the telomere lengths of
      antisense-epidermal growth factor receptor cells were shortened. In addition, the
      tumorigenicity of antisense-epidermal growth factor receptor cells was
      significantly inhibited. Taken together, there were strong correlations between
      tumorigenicity and epidermal growth factor receptor expression levels, and
      between tumorigenicity and telomerase activity. These results provide evidence
      that epidermal growth factor receptor plays an important role in the regulation
      of telomerase activity of glioma cells. Our findings provide new insights into
      both the biological functions of epidermal growth factor receptor and the
      regulation of telomerase activity. The inhibition of telomerase activity
      triggered by antisense-epidermal growth factor receptor treatment may reflect yet
      another mechanism of antisense-epidermal growth factor receptor approach in
      tumour suppression.

PMID- 11953894
TI  - Preclinical evaluation of the antiproliferative potential of STI571 in Hodgkin's
      disease.
AB  - STI571 is a selective tyrosine kinase inhibitor with proven therapeutic potential
      in malignancies expressing c-kit. A strong c-kit and stem cell factor expression
      was detected in the Hodgkin and Reed Sternberg cell line L1236, but not in 20
      primary cases of classical Hodgkin's disease. Proliferation of L1236 cells was
      neither affected by addition of stem cell factor nor by neutralising anti-stem
      cell factor antibodies or STI571. Results suggest that patients with Hodgkin's
      disease may not benefit from therapy with STI571.

PMID- 11953895
TI  - Induction of viral and tumour specific CTL responses using antibody targeted HLA
      class I peptide complexes.
AB  - The production of cytotoxic T cells with specificity for cancer cells is a
      rapidly evolving branch of cancer therapeutics. A variety of approaches aim to
      amplify anti-tumour cytotoxic T cell responses using purified peptides, tumour
      cell lysates or recombinant HLA/peptide complexes in differing antigen presenting
      systems. Using a two-step biotin-streptavidin antibody targeting system,
      recombinant HLA-class I/peptide complexes were attached to the surface of B cells
      via the anti-CD20 B9E9-scFvSA antibody-streptavidin fusion protein. Flow
      cytometry with a conformation dependant monoclonal antibody to HLA class I
      indicated that targeted HLA-class I/peptide complexes remain on the surface of B
      cells in culture for periods in excess of 72 h. PBMCs were stimulated in vitro
      for 8-14 days using the autologous B cells as antigen presenting cells. Following
      a single cycle of stimulation specific cytotoxic T cell responses to targeted HLA
      A2 complexes containing the M1, BMLF1 and Melan A peptides could be demonstrated
      by tetramer staining and Cr release assays. With the HLA-A2/BMLF1 complex up to
      2.99% of CD8+ve cells were tetramer positive producing 20% lysis (E : T 10 : 1)
      of CIR-A2 target cells in an in vitro cytotoxicity assay compared to baseline
      levels of 0.09% tetramer +ve and 2% lysis in the unstimulated population. PBMCs
      from a healthy donor treated with two cycles of stimulations with targeted HLA
      A2/Melan A complexes, demonstrated expansion of the melanA tetramer +ve
      population from 0.03% to 1.4% producing 15% lysis of Melan A pulsed target cells.
      With further consideration to the key variables of HLA/peptide complex density,
      the ratio of stimulator to effector cells and optimum cytokine support, this
      system should offer an easy and effective method for the in vitro amplification
      of specific cytotoxic T cell responses and warrants development for the in vivo
      induction of cytotoxic T cell responses in cancer therapy.

PMID- 11953896
TI  - Aminolaevulinic acid-induced photodynamic therapy: cellular responses to glucose
      starvation.
AB  - Photodynamic therapy is a cancer treatment based on the interaction of light,
      oxygen and a photosensitiser. Protoporphyrin. IX is an endogenous photosensitiser
      derived from the pro-drug aminolaevulinic acid. Tumours contain areas of hypoxia
      and hypoglycaemia. Tumour cells adapt to these conditions by stress protein
      induction which may induce resistance to cancer therapies. The effect of chronic
      hypoglycaemia on sensitivity to aminolaevulinic acid-induced photodynamic therapy
      in vitro was studied in MCF-7, human breast cancer cells. Following chronic
      exposure to 0, 1 or 25 mM, glucose, cells were treated with aminolaevulinic acid
      and the generation of intracellular protoporphyrin. IX measured by
      spectrofluorimetry. Aminolaevulinic acid-induced photodynamic therapy sensitivity
      was compared between cells following chronic exposure to 0, 1 or 25 mM glucose.
      Percentage cell survival was determined by clonogenic assay. Cells cultured in
      low glucose generated higher levels of protoporphyrin IX compared to standard
      glucose medium (0 mM glucose: 0.88 x 10(-5) ng cell(-1), 1 mM: 0.86 x 10(-5) ng
      cell(-1), 25 mM: 0.60 5x 10(-5) ng cell(-1), P<0.05). However, photodynamic
      therapy sensitivity was reduced in glucose deprived cells (0 mM glucose: 61%
      survival, 1 mM: 80.5% and 25 mM: 39.6%, P<0.05). Chronic exposure to low glucose
      induces photodynamic therapy resistance despite increased intracellular
      concentrations of protoporphyrin IX and may reflect cellular adaptation to
      chronic glucose deprivation.

PMID- 11953897
TI  - In vitro evaluation of amino acid prodrugs of novel antitumour 2-(4-amino-3
      methylphenyl)benzothiazoles.
AB  - Novel 2-(4-aminophenyl)benzothiazoles possess highly selective, potent antitumour
      properties in vitro and in vivo. They induce and are biotransformed by cytochrome
      P450 (CYP) 1A1 to putative active as well as inactive metabolites. Metabolic
      inactivation of the molecule has been thwarted by isosteric replacement of
      hydrogen with fluorine atoms at positions around the benzothiazole nucleus. The
      lipophilicity of these compounds presents limitations for drug formulation and
      bioavailability. To overcome this problem, water soluble prodrugs have been
      synthesised by conjugation of alanyl- and lysyl-amide hydrochloride salts to the
      exocyclic primary amine function of 2-(4-aminophenyl)benzothiazoles. The prodrugs
      retain selectivity with significant in vitro growth inhibitory potency against
      the same sensitive cell lines as their parent amine, but are inactive against
      cell lines inherently resistant to 2-(4-aminophenyl)benzothiazoles. Alanyl and
      lysyl prodrugs rapidly and quantitatively revert to their parent amine in
      sensitive and insensitive cell lines in vitro. Liberated parent compounds are
      sequestered and metabolised by sensitive cells only; similarly, CYP1A1 activity
      and protein expression are selectively induced in sensitive carcinoma cells.
      Amino acid prodrugs meet the criteria of aqueous solubility, chemical stability
      and quantitative reversion to parent molecule, and thus are suitable for in vivo
      preclinical evaluation.

PMID- 11953898
TI  - Expression pattern of the urokinase-plasminogen activator system in rat DS
      sarcoma: role of oxygenation status and tumour size.
AB  - The urokinase plasminogen activator system plays a central role in malignant
      tumour progression. Both tumour hypoxia and enhancement of urokinase plasminogen
      activator, urokinase plasminogen activator-receptor and plasminogen activator
      inhibitor type 1 have been identified as adverse prognostic factors. Upregulation
      of urokinase plasminogen activator or plasminogen activator inhibitor type 1
      could present means by which hypoxia influences malignant progression. Therefore,
      the impact of hypoxia on the expression pattern of the urokinase plasminogen
      activator system in rat DS-sarcoma in vivo and in vitro was examined. In the in
      vivo setting, tumour cells were implanted subcutaneously into rats, which were
      housed under either hypoxia, atmospheric air or hyperoxia. For in vitro studies,
      DS-sarcoma cells were incubated for 24 h under hypoxia. Urokinase plasminogen
      activator and urokinase plasminogen activator-receptor expression were analysed
      by flow cytometry. Urokinase plasminogen activator activity was measured using
      zymography. Plasminogen activator inhibitor type 1 protein levels in vitro and in
      vivo were examined with ELISA. PAI-1 mRNA levels were determined by RT-PCR. DS
      sarcoma cells express urokinase plasminogen activator, urokinase plasminogen
      activator-receptor, and plasminogen activator inhibitor type 1 in vitro and in
      vivo. The urokinase plasminogen activator activity is enhanced in DS-sarcomas
      compared to normal tissues and rises with increasing tumour volume. The
      oxygenation level has no impact on the urokinase plasminogen activator activity
      in cultured DS-sarcoma cells or in solid tumours, although in vitro an increase
      in plasminogen activator inhibitor type 1 protein and mRNA expression after
      hypoxic challenge is detectable. The latter plasminogen activator inhibitor type
      1 changes were not detectable in vivo. Hypoxia has been demonstrated to
      contribute to the upregulation of some components of the system in vitro,
      although this effect was not reproducible in vivo. This may indicate that the
      serum level of plasminogen activator inhibitor type 1 is not a reliable surrogate
      marker of tumour hypoxia.

PMID- 11953899
TI  - Gamma-heregulin has no biological significance in primary breast cancer.

PMID- 11953901
TI  - Thymidylate synthase polymorphism and survival of colorectal cancer patients
      treated with 5-fluorouracil.

PMID- 11953900
TI  - Early life exposure to oestrogen and testicular cancer risk: evidence against an
      aetiological hypothesis.

PMID- 11953903
TI  - Genetic risk factors of chronic obstructive pulmonary disease.
AB  - Cigarette smoking is the major risk factor for chronic obstructive pulmonary
      disease (COPD). However, only a minority of cigarette smokers develop symptomatic
      disease. Family and twin studies suggest that genetic factors also contribute to
      the development of COPD. We present a detailed literature review of the genes
      which have been investigated as potential risk factors for this disease.

PMID- 11953904
TI  - Influence of stapler haemorrhoidectomy on anorectal function and on patients'
      acceptance.
AB  - PRINCIPLES: Symptomatic haemorrhoids surgery has been shown to be the most
      successful and definite therapy. Recently a new method using a transanally
      inserted circular stapler has been presented for treatment of symptomatic
      prolapsing haemorrhoids. This prospective study investigated the influence of the
      stapling procedure on the anorectal function and patients' acceptance. METHODS:
      Eighteen consecutive patients (10 males, 8 females) mean age 44.7 years (range 18
      66) with symptomatic second (n = 3), third (n = 14), and fourth degree (n = 1)
      haemorrhoids were included. All patients underwent the day before and 8 weeks
      after the operation a standardised anal manometry using a water perfused system.
      Mean resting (MRAP) and mean maximal squeeze anal pressures (MSAP) were recorded.
      Volumes of initial rectal sensation (VIRS), constant rectal sensation (VCRS), and
      maximal tolerable volume (MTV) of a rectal balloon were assessed. Anorectal
      symptoms (bleeding, pain, faecal incontinence) were assessed in a standardised
      fashion preoperatively and 1, 8, and 12 weeks postoperatively. RESULTS: The
      stapling procedure led to no manometric or symptomatic change in anal sphincter
      function. Pre- and postoperative MRAP (91.7 mm Hg, SD 23.59 / 83.8 mm Hg, SD
      14.53, p = 0.053), MSAP (162.6 mm Hg SD 78.68 / 173.9 mm Hg, SD 69.93, p =
      0.162), VIRS (55.8 ml, SD 26.12 / 51.7 ml, SD 28.90, p = 0.410), VCRS (109.4 ml
      SD 41.67/ 96.4 ml, SD 38.44, p = 0.181), and MTV (204.7 ml SD 47.65/ 173.3 ml, SD
      43.22, p = 0.053) were similar. No symptoms of rectal pain or faecal incontinence
      were registered during follow up. Patients' acceptance and satisfaction for the
      operation were high. CONCLUSIONS: Stapling haemorrhoidectomy is a safe procedure
      which does not alter anorectal functions. Patients' acceptance and satisfaction
      are high.

PMID- 11953905
TI  - Prevalence of asymptomatic celiac disease in adolescents of eastern Switzerland.
AB  - BACKGROUND: The prevalence of symptomatic CD in Switzerland is thought to be 1 in
      1,000 inhabitants. As in other countries, oligo- and asymptomatic CD is being
      diagnosed with increasing frequency in all age groups. AIM: To assess the
      prevalence of asymptomatic CD in adolescents in eastern Switzerland. METHOD:
      Between September 1999 and July 2000 total serum IgA titres, anti-endomysium IgA
      (EMA) titres and anti-human tissue transglutaminase IgA (hTTG) titres were
      measured in the serum of healthy 11- to 18-year-old Swiss lower and upper
      secondary school students. RESULTS: Of the 1,450 students (871 f = 60.1%, CI 95%)
      tested, 11 (10 f) had elevated levels of both EMA and TTG. The diagnosis of CD
      was confirmed in eight of these students by mucosal jejunal morphology (Marsh
      III); one exhibited normal histology. Two of the 11 students refused to undergo
      mucosal biopsy. None of the students, however, had symptoms suggestive of CD, nor
      were they stunted or underweight, and none of them had family members with known
      CD. All of the eight students with enteropathy went on a glutenfree diet and felt
      subjectively better than on a normal diet. Of the remaining students, 38 (2.6%)
      had family members with known CD. None of those with the relevant family history
      had elevated EMA or TTG levels. CONCLUSION: Asymptomatic CD is common. It occurs
      in 1 in 132 (0.75%) Swiss adolescents. The absence of subjectively recognisable
      symptoms suggestive of family history or other risk factors makes it difficult to
      diagnose this type of CD.

PMID- 11953906
TI  - Graves' ophthalmopathy.

PMID- 11953907
TI  - ST-segment re-elevation unrelated to left ventricular ejection fraction or volume
      after anterior wall acute myocardial infarction treated with successful
      reperfusion.
AB  - Ventricular remodeling is a major determinant of the long-term prognosis of
      patients with acute myocardial infarction (AMI). No previous study examined the
      relation of ST-segment re-elevation to left ventricular (LV) volume and function
      in patients with successful reperfusion. We examined the relation of ST-segment
      re-elevation to LV function and volume indices in 51 patients with anterior wall
      AMI who underwent successful reperfusion by direct coronary angioplasty. A 12
      lead electrocardiogram was recorded once a day until 7 days after the onset of
      AMI. ST-segment shift was measured and Sigma ST was defined as the sum of ST
      segment elevation obtained from leads V2, V3, and V4. ST-segment re-elevation was
      defined as present when the difference between maximal and minimal Sigma ST
      (Delta ST) was >0.3mV. LV indices were obtained from left ventriculography
      performed approximately 1 month after the onset of AMI. ST-segment re-elevation
      was observed in 15 patients (29%). No significant differences were observed
      between the ST- re-elevation group and non-ST-re-elevation group in LV ejection
      fraction (49.4+/-14.0 vs. 51.2+/-11.5%), LV end-systolic volume index (35.8+/
      13.1 vs. 33.8+/-12.5 mL/m(2)) or LV end-diastolic volume index (69.7+/-12.8 vs.
      68.3+/-14.4 mL/m(2)). The difference between maximal and minimal Sigma ST (Delta
      ST) was not significantly correlated with any LV index examined. In conclusion,
      the present study revealed that ST-segment re-elevation after successful
      reperfusion in anterior wall AMI patients was not related to LV volume or
      function, indicating that ST-re-elevation is not a clinically meaningful
      indicator of LV remodeling.

PMID- 11953908
TI  - Assessment of the RR versus QT relation by a new symbolic dynamics method. Gender
      differences in repolarization dynamics.
AB  - A new method based on symbolic dynamics was applied to assess RR-QT dynamics and
      to compare gender differences. Segments of 10,000 RR and QT from the night were
      selected. The values of RR and QT were coded as follows. Each RR and QT interval
      was compared with their means in the last 50 beats [xRR, xQT]; when the interval
      was larger than x + delta then it was coded as a "2", where delta is the
      tolerance parameter; when it was less than x - delta-the code was a "0"; when it
      was larger than x-delta and and the less than x+delta-then it was coded as a "1."
      The tolerance parameter "delta" was equal to 10 ms for RR and 4 ms for QT. We
      obtained pairs of symbols representing the values of RR and QT-symbolic words.
      The results were presented in form of the probability density of the symbolic
      words. Mean RR, mean QT, SDRR, SDQT, QTc (Bazett formula) were also calculated.
      Electrocardiogram data of healthy individuals: 20 women and 20 men (mean age 39
      +/- 12) were analyzed. There were significant gender differences in RR-QT
      dynamics. During heart rate acceleration the probability of QT shortening (the
      probability of the word "00") was higher in men than in women (P =.003). During
      heart rate deceleration QT lengthening (the word "22") was more frequently
      observed in men than in women (P =.003) as well. The QT reaction to RR interval
      changes is less complex in women than in men. In discriminant analysis, when QTc
      was ignored in the model, the RR-QT dynamics separated genders with 67% accuracy
      (chi(2) = 9.1, P <.003). RR-QT dynamics can be analyzed with symbolic dynamics
      methods. The gender differences in repolarization are not only due to QTc
      duration alone but also result from the dependence of the duration of QT on the
      RR duration.

PMID- 11953909
TI  - Moving dipole analysis of normal and abnormal ventricular activation by
      magnetocardiography.
AB  - The current source during ventricular excitation of the in situ heart has not
      been well characterized. We analyzed current dipoles of ventricular excitation by
      magnetocardiography (MCG) in 16 healthy subjects and 10 patients with the Wolff
      Parkinson-White syndrome or premature ventricular contraction. Single current
      dipoles were estimated by MCG with the spatial position, direction, and strength
      in the initial 40 ms of QRS (moving dipole analysis). In 12 of the 16 healthy
      subjects, the origin of current dipoles moved consecutively from the initial
      position with the increase in the peak strength at 30 ms of QRS. In the other 4
      healthy subjects, dipoles moved discontinuously jumping to the right-anterior
      thorax at 17.8 ms (mean). In abnormal ventricular excitation, the dipoles
      remained in the initial position with little movement, smaller strength of dipole
      than that of normal with a delayed peak time. The moving dipole analysis can be
      applied to determine spatial distribution of normal and abnormal excitation
      sources at the initial phase of ventricular depolarization in the in situ heart.

PMID- 11953910
TI  - Effect of electrolyte and pH changes on the sinus node pacemaking in humans.
AB  - The importance of plasma electrolytes and pH levels in determining heart rate is
      not yet well grounded. Hemodynamic and biochemical data were collected during 8
      purely diffusive hemodialysis, which allowed changes in extracellular fluid to be
      achieved without eliciting notable changes in the autonomic control of heart
      rate. A significant heart rate increase was obtained after potassium decrease and
      calcium and pH increase, with no significant variations in indices of autonomic
      activity. Model-based computer simulations were then used to separate the effects
      of each ionic species and pH on sinus node cell pacemaker activity. This analysis
      revealed that changes in physiological range of potassium, calcium, and pH could
      cause large heart rate variations from 60 to 90 bpm. Nonlinear heart rate
      dependence on potassium was also recognized. It was concluded that electrolyte
      and pH changes in physiological range have an important, complex, impact on the
      pacemaking rhythm independently of autonomic outflow.

PMID- 11953911
TI  - Digitized electrocardiograms recorded with bipolar right-infraclavicular leads
      compared to electrocardiograms recorded with unipolar chest V leads and bipolar
      lead II.
AB  - This article presents a method for the evaluation of cardiac depolarizations in a
      relatively short time with a minimum number of electrodes. With the negative
      electrode attached to the right infraclavicular region, voltage variations on the
      chest surface exhibit larger excursions than do the usual unipolar leads. Peak
      voltages of the PQRST waveforms measured on 12 normal patients by both methods
      were similar in polarity but were statistically significantly higher in the right
      infraclavicular leads. Data are presented on 21 normal patients, which show that
      digitized signals allow for an expanded time-scale leading to higher resolution
      of rate of change and onset and offset times. The digitized signals also more
      clearly define notches that distort the QRS complex. In 55 cardiac patients, the
      12-lead unipolar electrocardiograms were visually compared to digitized
      electrocardiograms recorded by using the bipolar right infraclavicular leads. The
      authors suggest that RIC leads would be most useful in the design of a pocket
      sized digitizing bipolar-lead electrocardiograph.

PMID- 11953912
TI  - Circadian variation of short-lasting asymptomatic paroxysmal supraventricular
      tachycardia.
AB  - This study determines the circadian variation of transient asymptomatic
      paroxysmal supraventricular tachycardia (PSVT). A total of 416 asymptomatic PSVT
      episodes (> or = 10 consecutive supraventricular beats) recorded in 62 patients
      were obtained from Holter monitoring. The incidence of the onset of PSVT was
      counted at the 1-hour interval. The duration (beats) and rate (beats/min) of PSVT
      and the preceding heart rate were also evaluated. The circadian variations of the
      onset, duration, and rate of PSVT were analyzed by the single cosinor method. The
      incidence of the onset of PSVT showed a significant circadian variation (P =
      .001); with high incidence in the daytime and low at nighttime. The rate and
      duration of PSVT also showed significant circadian variation (P = .02), faster
      and longer in daytime and slower and shorter at night, respectively. The rate (r
      = .45, P < .001) and duration (r = .22, P < .001) of PSVT correlated
      significantly with the preceding heart rate. Our findings suggest that the onset
      and persistence of short-lasting asymptomatic PSVT exhibit a circadian pattern
      and that autonomic tone might play an important role in the genesis of this form
      of PSVT.

PMID- 11953913
TI  - Abrupt and sustained shortening of the AV delay of a DDDR pacemaker during stable
      sinus rhythm.
AB  - This article describes the abrupt and sustained shortening of the sensed AV delay
      in a patient with an Intermedics Marathon DDDR pacemaker programmed to the
      SmarTracking function, which prevents tracking of inappropriate atrial rates. The
      AV delay remained extended and stable when the sinus cycle became equal to the
      prevailing upper rate interval determined by sensor input. When the sinus rate
      remained stable, the AV delay returned abruptly to its shorter programmed
      duration at the end of the tachycardia terminating algorithm and remained
      constant afterwards. This behavior is caused by a pacemaker Wenckebach upper rate
      response related to the slow prevailing upper rate at rest provided by sensor
      input to the SmarTracking function of the pulse generator.

PMID- 11953914
TI  - Electrocardiographic demonstration of intermittent left bundle branch block
      because of the "linking" phenomenon.
AB  - The authors describe a patient who showed intermittent left bundle branch block
      at a slow heart rate. The perpetuation of left bundle branch block is suggested
      because of rate dependent bundle branch block and trans-septal retrograde
      concealed penetration by the contralateral bundle as it is resolved by a
      premature ventricular extrasystole. This phenomenon is called "linking." This
      case report aims to present and emphasize this interesting phenomenon.

PMID- 11953915
TI  - Bundle branch block on alternate beats: by what mechanism?
AB  - In a patient with right bundle branch block occurring on alternate beats during
      regular sinus rhythm, the conduction disturbance disappeared during
      hyperventilation induced increase in heart rate, and reappeared with slight
      slowing of the sinus rate due to carotid sinus massage. The following mechanisms
      are potentially involved in the electrogenesis of bundle branch block alternans
      with regular RR intervals: a) phase-3 2:1 bidirectional block; b) phase-3
      antegrade block with retrograde concealed activation of the involved bundle
      branch and subsequent "supernormal" conduction; and c) phase-4 antegrade block
      with transseptal retrograde concealed invasion of the affected bundle branch by
      impulses traversing the unimpaired bundle branch. Analysis of the tracing
      excluded both mechanisms a and b and favored bradycardia-dependent right bundle
      branch block as a key to explain the alternate pattern of intraventricular
      conduction.

PMID- 11953916
TI  - Apparent bradycardia-dependent advanced second-degree atrioventricular block.
AB  - A 65-year-old man with repeated chest discomfort and dizzy spells was transferred
      by an emergency car. On the way to hospital, his pulse was palpable as regular 4
      to 5 beats followed by an unpalpable period of about 4 s. His
      electrocardiographic monitor showed that 4 to 5 sinus QRS complexes were followed
      by consecutive 3 to 4 blocked sinus P waves, which occurred repeatedly. When PP
      intervals gradually shortened during inspiration, sinus impulses were conducted
      to the ventricles, whereas when PP intervals lengthened during expiration, 3 to 4
      sinus impulses were blocked in succession. An attempt was made to explain the
      mechanism for such apparent bradycardia-dependent atrioventricular block by using
      the concepts of periodic increases in vagal tone due to respiration and concealed
      electrotonic conduction of blocked impulses. Such a peculiar form of advanced
      second-degree atrioventricular block has never been reported before.

PMID- 11953917
TI  - Global and local dispersion of ventricular repolarization: endocardial monophasic
      action potential mapping in swine and humans by using an electro-anatomical
      mapping system.
AB  - This article evaluates whether the global dispersion of ventricular
      repolarization (DVR) can be estimated from measurements between a few adjacent or
      remote sites. Monophasic action potentials (MAP) were recorded from 61 +/- 18
      left (LV) or right ventricular (RV) sites in 10 pigs and 44 +/- 16 LV, or RV
      sites in 8 patients by using the CARTO mapping system. MAP duration (MAPd) and
      end-of-repolarization time were calculated at each site and 13 repolarization
      maps from pigs and 10 from patients were reconstructed. Global dispersions in
      MAPd and EOR over the LV or RV were compared with the adjacent DVR among 3 - 7
      MAPs in areas > or = 0.7 and < or = 1 cm(2) and with the remote DVRs between 2
      MAPs with the greatest activation time difference (remote DVR1) and between the
      apical and laterobasal LV or RV (remote DVR2). The adjacent dispersions in end-of
      repolarization and MAPd were significantly smaller than the global ones, 13 +/- 3
      and 12 +/- 3 ms vs. 44 +/- 9 and 42 +/- 12 ms in pigs and 13 +/- 7 and 14 +/- 8
      ms vs. 72 +/- 24 and 66 +/- 22 ms in patients. The remote DVR1 (30 +/- 8 and 17
      +/- 10 ms in pigs and 40 +/- 28 and 28 +/- 17 ms in patients) and remote DVR2 (16
      +/- 7 and 11 +/- 10 ms in pigs and 35 +/- 24 and 21 +/- 21 ms in patients) were
      also significantly smaller than the global DVRs. In conclusion, global DVR is
      poorly estimated from MAP recordings from a few adjacent or remote sites,
      suggesting the importance of obtaining global information in evaluating DVR.

PMID- 11953918
TI  - Electrocardiographic patterns of the Brugada syndrome in 2 young patients with
      pectus excavatum.
AB  - I hypothesized that thoracic deformity of pectus excavatum may induce the Brugada
      type electrocardiogram (ECG) pattern because of the presumed chronic injury to
      the right ventricle. Thus, I examined the 5 outpatients with pectus excavatum to
      determine the presence or absence of the ECG pattern of Brugada syndrome. Four of
      5 study patients accompanied incomplete right bundle branch block pattern. Among
      these 4, 2 patients presented with Brugada-type ECG pattern, ie, right bundle
      branch block pattern and ST-segment elevation in the right precordial ECG leads.
      Both of them with Brugada-type ECG had no past history of syncope, family history
      of sudden death, or malignant arrhythmias on the 24-h Holter ECG recording. These
      observations suggest that clinically benign Brugada-type ECG pattern may appear
      in some patients with pectus excavatum.

PMID- 11953920
TI  - Probiotics and prebiotics: A brief overview.
AB  - Probiotics and prebiotics are 2 food ingredients that confer physiologic effects
      through the gastrointestinal tract. Probiotics have been defined as viable
      microorganisms that (when ingested) have a beneficial effect in the prevention
      and treatment of specific pathologic conditions. These microorganisms are
      believed to exert biological effects through a phenomenon known as colonization
      resistance, whereby the indigenous anaerobic flora limits the concentration of
      potentially pathogenic (mostly aerobic) flora in the digestive tract. Other modes
      of action, such as supplying enzymes or influencing enzyme activity in the
      gastrointestinal tract, may also account for some of the other physiologic
      effects that have been attributed to probiotics. Conversely, prebiotics are
      nondigestible food ingredients that beneficially affect host health by
      selectively stimulating the growth and/or activity of 1 or a limited number of
      bacteria in the colon. The prebiotic, fructooligosaccharide (FOS), is found
      naturally in many foods, such as wheat, onions, bananas, honey, garlic, or leeks.
      They can also be isolated from chicory root or synthesized enzymatically from
      sucrose. Fermentation of FOS in the colon results in a large number of
      physiologic effects including increasing the numbers of bifidobacteria in the
      colon, increasing calcium absorption, increasing fecal weight, shortening of
      gastrointestinal transit time, and possibly lowering blood lipid levels. Other
      effects that have been observed in animal models include an increase in cecal
      weight and an increase in fecal nitrogen excretion. The increase in
      bifidobacteria has been assumed to benefit human health by producing compounds to
      inhibit potential pathogens, by reducing blood ammonia levels, and by producing
      vitamins and digestive enzymes.

PMID- 11953921
TI  - Cross-sectional relationship between dietary protein and energy intake,
      nutritional status, functional status, and comorbidity in older versus younger
      hemodialysis patients.
AB  - OBJECTIVE: To evaluate the dietary energy intakes (DEI) and dietary protein
      intakes (DPI) of older (> or = 65 years), middle-aged (50 to 64 years), and
      younger (< 50 years) maintenance hemodialysis patients enrolled in the
      Hemodialysis (HEMO) Study, and to describe the relationship between age,
      nutritional status, functional status, and comorbidity. DESIGN: A cross-sectional
      analysis of the first 1,397 participants in baseline (before randomization) was
      performed. MAIN OUTCOME MEASURES: DEI and DPI, serum albumin, creatinine, total
      cholesterol, normalized protein catabolic rate (nPCR), equilibrated nPCR (enPCR),
      functional status, and comorbidities. RESULTS: Mean DEI, DPI, serum albumin,
      creatinine, nPCR, and enPCR were significantly lower in the older compared with
      the younger patients, despite similar doses of dialysis as measured by
      equilibrated Kt/V. Mean DEI, DPI, nPCR, and enPCR were not significantly
      different between the middle-aged and older patients, whereas albumin and
      creatinine were significantly lower in the older patients. Mean dry weight and
      percent of standard body weight in the younger and older patients were similar.
      In all groups, mean DEI was lower than both the HEMO study's standard of care
      (SOC) and the Kidney Disease Outcomes Quality Initiative (K/DOQI) nutrition
      recommendations, whereas mean DPI was lower than the SOC and K/DOQI
      recommendations only in the middle-aged and older patients. Middle-aged and older
      patients had higher cholesterol, lower functional status, and more comorbidities
      than the younger patients. CONCLUSION: Middle-aged and older maintenance dialysis
      patients may be at greater risk for developing protein-energy malnutrition than
      their younger counterparts. Inadequate DEI and DPI reported in middle-aged and
      older patients were associated with lower levels of biomarkers of nutritional
      status, lower functional status, and higher comorbidities than in the younger
      patients.

PMID- 11953922
TI  - Severe dietary protein restriction in overt diabetic nephropathy: benefits or
      risks?
AB  - OBJECTIVE: To evaluate whether restricting protein intake may delay the
      progression of chronic renal failure caused by overt diabetic nephropathy and
      also whether this increases the risk of malnutrition. DESIGN: Prospective
      clinical trial. SETTING: Nephrology outpatients. PATIENTS: Sixty-nine patients
      (32 affected by type 1 and 37 by type 2 diabetes, all treated with insulin)
      affected by both overt diabetic nephropathy and hypertension. INTERVENTION: The
      study was started once hypertension and glycemia had been under control for at
      least 3 months. Two groups of patients, matched for similar mean glomerular
      filtration rate value and nutritional status, were studied: a low-protein diet
      (0.6 g/kg/d) was randomly prescribed to 35 patients, whereas in the other 34
      patients a free diet intake was maintained for 12 months. MAIN OUTCOME MEASURE:
      Renal function and nutritional status. RESULTS: The protein intake was
      significantly different in the 2 groups of patients, whereas the average decline
      of glomerular filtration rate during the follow-up was comparable. In the low
      protein diet group, serum prealbumin concentration significantly decreased after
      9 months, whereas serum albumin decreased at the end of the study. CONCLUSION:
      Severe dietary protein restriction does not seem to delay the progression of
      renal disease in patients with overt diabetic nephropathy, whereas it may induce
      malnutrition.

PMID- 11953923
TI  - Nutrition project in a remote Australian aboriginal community.
AB  - Much of the ill health of Australian indigenous populations can be attributed to
      diet-related diseases. This community nutrition project is part of a wider renal
      screening and prevention program based in the Umoona aboriginal community in
      Coober Pedy in South Australia's far north. The nutrition project facilitates the
      capacity of the Umoona aboriginal community to identify and redress nutrition
      related issues considered important in improving their overall health status.
      Project nutritionists developed and implemented a specialized nutrition training
      program with the Umoona aboriginal health workers. The nutritionists were
      responsive to requests from community groups to provide nutrition expertise and
      support in program development. Individual nutrition counseling for adults and
      children taking part in renal health screening was also provided. The aboriginal
      health workers reported increased nutritional knowledge and confidence in
      addressing nutrition-related issues within the community after nutrition
      training. Individual consultations and partnerships formed with community groups
      have increased awareness and prompted action to address the importance of
      nutrition in renal disease and overall health in the Umoona community.

PMID- 11953924
TI  - Computers in clinical practice: screening renal patients for abnormal
      biochemistry and malnutrition.
AB  - OBJECTIVE: Develop and compare a computer program (CP) and a screening tool (ST)
      to determine the best method of identifying patients undergoing hemodialysis (HD)
      who are at risk of malnutrition. Investigate the benefits of using the CP to
      screen biochemical test results of patients undergoing HD, continuous ambulatory
      peritoneal dialysis (CAPD), nephrology patients, and transplant recipients for
      abnormal levels, such as hyperkalemia. DESIGN: The CP was designed by using the
      program Proton (Clinical Computing Clinical Information Systems, Middlesex,
      England). Proton can automatically download biochemical results from pathology,
      making it possible to generate a list of patients with results outside a desired
      biochemical range in accordance with national renal standards for adult patients.
      Biochemical measures of nutritional status were used to define malnutrition as 2
      or more results outside of these parameters: 10% weight loss; Kt/V < 1.1;
      predialysis urea, <20 mmol/L; phosphate, <0.75 mmol/L; and potassium, <3.3
      mmol/L. One hundred eighty-four HD patients were incidentally screened for their
      risk of malnutrition by using both the CP and the ST. SETTING: Richard Bright
      Renal Unit, Bristol, England, and 4 satellite HD units in Southwest England.
      PATIENTS: Three thousand five renal outpatients, including 468 patients with
      diabetes, had blood test results screened by the CP for abnormal levels. This
      included 235 HD patients (unit A, n = 32; unit B, n = 58; unit C, n = 70; Unit D,
      n = 24; home HD unit, n = 51), 88 CAPD patients, 416 transplant recipients, and
      2,266 nephrology patients. MAIN OUTCOME MEASURE: The CP and the ST were compared
      with standardized dietetic assessments (SDAs) for validity. In the clinic
      setting, the length of time taken to review biochemical test results was measured
      before and after implementation of the CP. RESULTS: The CP identified 36% of HD
      patients at risk of malnutrition, compared with 20% by the ST and 42% by SDA.
      However, only 57% of the STs were completed. The CP found 42% of transplant
      recipients and 92% of nephrology patients have glycosylatid hemoglobin levels >7,
      and 16% of HD patients have fluid weight gains >3 kg on 4 or more occasions in a
      month. CONCLUSION: Using the present parameters, the CP is not sensitive enough
      to correctly identify all HD patients at risk of malnutrition. Screening for
      serum cholesterol, prealbumin, protein equivalent of total nitrogen appearance,
      and C-reactive protein levels should be incorporated into the CP to compare it
      with a simple, inexpensive, and reproducible screening tool, such as subjective
      global assessment, to identify malnutrition in patients undergoing dialysis. The
      CP improves time management and rationalization of dietetic activity by screening
      abnormal biochemistry levels. Renal dietitians are urged to investigate the
      practicalities and the benefits of computers in clinical practice because early
      identification of malnutrition in patients allows dietitians to work in a more
      proactive manner.

PMID- 11953925
TI  - Anthropometric and growth assessment of children receiving renal replacement
      therapy in Malaysia.
AB  - OBJECTIVE: To report on the anthropometric and growth status of children
      receiving renal replacement therapy (RRT) in Malaysia. DESIGN: Cross-sectional
      study with some retrospective elements. SETTING: Outpatients' clinics in a major
      referral hospital in Malaysia. PATIENTS: Fifteen renal transplants (mean age,
      13.3 +/- 2.8 years) and 35 continuous ambulatory peritoneal dialysis (CAPD)
      patients (mean age, 12.6 +/- 3.0 years) participated. The RRT period ranged
      between 3 months to 6 years for both groups. INTERVENTION: None. MAIN OUTCOME
      MEASURES: Body mass index (BMI), percent body fat (% BF), triceps skinfold (TSF),
      mid upper-arm circumference (MUAC), arm muscle area (AMA), and z scores for
      height and weight. RESULTS: BMI for age indicated 7% of transplant subjects (TS)
      versus 40% of CAPD subjects were below the 5th percentile, whereas only 7% of TS
      were above the 95th percentile. % BF was higher for TS compared with the CAPD
      group for both sexes (boys, 19.5% and girls, 29.8% v boys, 12.4% and girls,
      21.5%). Despite higher percentiles for TSF, transplant subjects still showed
      depleted muscle mass based on MUAC and AMA. z scores for height showed 93% of
      transplant subjects and 62% of CAPD subjects below -2 standard deviation (SD),
      whereas for weight these were 27% and 54%, respectively. Sixty-four percent of TS
      experienced catch-up growth for height and 86% for weight. These percentages were
      approximately halved for the CAPD group (32% and 43%, respectively). CONCLUSION:
      Patterns of growth and body composition appear distinctly different with the
      different RRT modalities. Serial anthropometric evaluation appears vital in pre-
      and post-RRT monitoring in pediatric renal populations.

PMID- 11953926
TI  - Short-term effects of angiotensin II receptor blockade in patients with primary
      glomerulonephritis: pilot study.
AB  - OBJECTIVE: There is evidence that angiotensin II, the main effector of renin
      angiotensin system, plays a crucial role in the pathogenesis of chronic renal
      injury. Angiotensin II type 1 (AT-1) receptor blockers reduce renin-angiotensin
      system activity by blocking the receptor, the activation of which is responsible
      for the majority of deleterious angiotensin II effects. The aim of the present
      study was to investigate renal and metabolic effects of specific AT-1 receptor
      blocker-losartan in patients with primary glomerulonephritis. DESIGN: Pilot
      clinical study. SETTING: Department of Nephrology, Transplantology and Internal
      Medicine, Medical University of Gdansk, Poland. PARTICIPANTS: Fifteen patients
      aged 43.3 +/- 11.3 years with primary glomerulonephritis confirmed by renal
      biopsy were studied. INTERVENTION: Creatinine clearance, urinary excretion of
      protein and uric acid, urinary activity of N-acetyl-beta-D-glucosaminidase, and
      serum concentrations of lipids, protein, and uric acid were evaluated before and
      after 3 months of losartan (Cozaar; Merck Sharp & Dohme, Harlow, Essex, United
      Kingdom) treatment at a dose of 25 mg daily. RESULTS: We found a significant
      reduction of urinary excretion of protein (P <.008; average, 32%). Results also
      revealed a decrease of serum uric acid level (P <.01), probably as a consequence
      of elevated uric acid urinary excretion (P <.09). No significant changes in
      creatinine clearance, N-acetyl-beta-D-glucosaminidase activity, protein, or lipid
      levels were observed. CONCLUSION: We concluded that losartan treatment at a small
      dose of 25 mg daily produces antiproteinuric effect without adverse effects,
      notably with no decrease of glomerular filtration, and simultaneously induces
      beneficial changes in purine metabolism.

PMID- 11953927
TI  - Impact of a high-dependency care area on the nutritional management of patients
      with acute uremia.
AB  - At this institution, all non-intensive care unit (ICU)-based patients with acute
      uremia were previously managed on the general nephrology ward, and there were
      concerns that these patients may not have been benefiting from optimal
      management, particularly with regard to nutrition. In 1998, a renal high
      dependency care (RHDC) unit was established within the ward, providing
      opportunity to compare the clinical management and outcomes of acutely uremic
      patients in 2 annual cohorts that were admitted both before and after
      implementation of the RHDC unit. Retrospective case reviews complemented data
      collected prospectively on the unit since 1995. There were 108 patients included
      from 1995 to 1996 and 86 patients included from 1998 to 1999; no patients were
      excluded, but a few case records were unobtainable. Both patient groups were
      demographically similar (median age, 68 years pre-RHDC, 62.5 years with the RHDC
      unit), and initial illness severity/comorbidity showed no significant
      differences. Nutritional support increased significantly (P <.05) from 22.4% in
      1995 to 1996 to 38.4% of patients in 1998 to 1999, reflecting increased oral
      supplementation. Dialysis requirements were similar (60.2% v 63.5%). The
      proportion of patients requiring admission to the ICU (17.6% v 8.1%) and the
      total number of ICU bed days used (195 v 86) was reduced in 1998 to 1999. Cost
      analysis showed little overall difference between the 2 cohorts; the actual cost
      of improved nutritional management was negligible. The RHDC area and its nurse
      based protocols have increased nutritional support for acutely uremic patients,
      allowing a reduction in ICU usage without any worsening in outcomes.

PMID- 11953928
TI  - Patient page. Ways to increase protein intake.

PMID- 11953929
TI  - Message from the chairperson.

PMID- 11953930
TI  - Measurement and the epidemiology of childhood trauma.
AB  - A review dealing with the epidemiology of traumatic experiences in childhood and
      adolescence will be of limited use without some attention being devoted to
      various demanding issues of measurement that are involved. The relevant
      literature on such experience is now large, with most research based on the use
      of standardized questionnaires. Although this has by and large been good enough
      to open up the field as a research enterprise, the task of establishing causal
      mechanisms in areas such as psychopathology is unlikely to flourish without a
      much greater investment in interview-based instruments using investigator-based
      ratings. Here research on the causative role of life events in general in the
      onset and course of psychiatric and physical disorder in both childhood and
      adulthood has a good deal to offer. Within the context of this emphasis on the
      importance of measurement various issues are discussed, such as the need to take
      account of nonabusive experience, particularly of correlated experiences such as
      parental neglect, the importance of obtaining time-based data and the need to
      take a population perspective where issues of prevalence are concerned.

PMID- 11953931
TI  - Psychiatric morbidity in adult survivors of childhood trauma.
AB  - This review focuses on child sexual abuse (CSA) as a prototype of childhood
      trauma and evaluates the evidence on psychiatric morbidity in adult survivors. An
      association between CSA and a wide range of psychiatric morbidity has been
      consistently documented in general population studies. The interpretation of this
      observed association is fraught with uncertainty that stems primarily from: (1)
      the retrospective nature of the data on CSA from adults' reports on their early
      experiences; (2) the adverse family context in which it occurs, which presents a
      major challenge for evaluating the effect of CSA per se; (3) the well documented
      lifetime comorbidity among psychiatric disorders, which leaves open questions
      about the specificity of CSA outcomes in adulthood. Twin study methods offer a
      solution to the problem of the familial context of CSA. Ascertainment of age of
      onset of adult disorders in future studies would increase the utility of findings
      for formulating psychological and biological causal models on the CSA-adult
      disorders connection. However, the retrospective nature of data on child abuse,
      because of legal and ethical restraints on research on children, is a formidable
      obstacle to advancing knowledge in this field.

PMID- 11953932
TI  - Neurobiology of early life stress: rodent studies.
AB  - It is now clear that early experience influences the long-term development of
      behavioral, neuroendocrine, and cognitive systems in a number of animal species.
      This article examines the effects of early life stress on the development of the
      rodent. Postnatal maternal separation is often used as a potent early life
      stressor, and some of the major findings from these studies are discussed. A
      majority of these studies have shown that early life stress can lead to a
      heightened stress response when maternally deprived rodents are tested as adults.
      The effects of early life stress on the development of brain structures involved
      in regulating the stress response as adults are also discussed. Finally the
      influence of both genetics and maternal style are mentioned in relation to their
      ability to alter the effects of early life stress.

PMID- 11953933
TI  - Neurobiology of early life stress: nonhuman primate models.
AB  - Numerous studies have shown that early life stress in nonhuman primates produces
      profound and long-lasting changes in behavior and biological function. We review
      several aspects of the neurobiology of early life stress, focusing on nonhuman
      primate experimental paradigms. There is experimental evidence that even prenatal
      stress can produce profound alterations in biological factors such as regulation
      of the hypothalamic-pituitary-adrenal (HPA) axis, biogenic amines, and immune
      function, as well as in behavioral measures of attention and sociability. An
      ongoing struggle in research studies is defining the relative contributions of
      nature and nurture in mediating the long-term effects of stress. Studies of
      social support contend that this has the capacity to buffer the deleterious
      effects of stressful early rearing environments, whereas social deprivations
      appear to have negative behavioral and medical outcomes, most notably deficits in
      immune function. From studies involving variable foraging demand (VFD)-reared
      nonhuman primates and other models, we suggest that many of the behavioral and
      biochemical changes produced resemble those seen in humans who suffer from
      depressive and anxiety conditions. Finally, there appears to be remarkable
      consistency of key neurobiological findings across species.

PMID- 11953934
TI  - Neuroimaging of childhood trauma.
AB  - Childhood abuse is a major public health problem affecting as many as a third of
      children in this country today at some point before their 18(th) birthday. The
      effects of childhood trauma on the brain are increasingly an area of interest. In
      trying to understand the effects of early stressors on the brain we use animal
      models of early stress to guide the development of hypotheses. An important
      potential tool in understanding the effects of abuse on the brain is
      neuroimaging. Neuroimaging studies in traumatized children are in a relative
      state of infancy. A number of methodological and ethical issues make this a
      difficult area for research, including problems ranging from patient motion
      during scanning to the ethical issues of the duty to report abuse and working
      with child protective services. Some studies have shown that adults abused as
      children have smaller volume of the hippocampus, a brain area involved in
      learning and memory, as measured with magnetic resonance imaging (MRI). One study
      in children with posttraumatic stress disorder (PTSD) did not find smaller
      hippocampal volume, but did find smaller brain volume and corpus callosum.
      Functional neuroimaging studies are consistent with alteration in function and
      structure of medial prefrontal cortex and hippocampus in patients with childhood
      sexual trauma and PTSD. These initial results suggest that childhood abuse in the
      setting of PTSD is associated with long-term changes in brain structure and
      function.

PMID- 11953935
TI  - Maternal depression: a child's first adverse life event.
AB  - Can the effects of maternal depression upon offspring development be extrapolated
      to the prebirth environment, making it the earliest of adverse life events?
      Increasing clinical and laboratory data indicate that maternal stress and
      depression during critical developmental windows carry a diverse array of harmful
      sequelae for the offspring. The effects witnessed in animal research include
      neurobiological and behavioral alterations that persist into adulthood.
      Paralleling the preclinical literature are human studies indicating similar acute
      effects. The clinical implications for the psychiatric treatment of depressed
      women who have children will be discussed.

PMID- 11953936
TI  - Psychotherapeutic approaches with survivors of childhood trauma.
AB  - The development and evaluation of psychotherapeutic approaches for survivors of
      childhood trauma has been complicated by numerous conceptual and methodological
      challenges. Randomized controlled clinical trials are rare, and most of these
      test cognitive behavioral therapy with sexually abused children. This article
      reviews psychosocial (nonpharmacological) treatment approaches with child and
      adult survivors of childhood trauma, highlighting methodologically sound studies
      of treatment efficacy. Implications of efficacy data for clinical practice and
      future research are discussed.

PMID- 11953937
TI  - Pharmacotherapy for survivors of childhood trauma.
AB  - Research over the past decade and a half has established the efficacy of
      pharmacotherapy as an important adjunctive treatment for trauma in conjunction
      with either cognitive behavior therapy or psychoanalytic psychotherapy.
      Medication is often effective in reducing post-traumatic stress symptoms as well
      as treating a number of commonly comorbid conditions such as depressive and
      anxiety disorders. The current medications of choice are the selective serotonin
      reuptake inhibitors (SSRI), which are beneficial for posttraumatic
      reexperiencing, hyperarousal, and avoidant symptoms. Other medication classes
      including non-SSRI antidepressants, mood stabilizers, anticonvulsants, and anti
      adrenergic agents have shown efficacy for some trauma symptoms. Because
      beneficial responses may be slow to appear, pharmacotherapy of trauma requires a
      medication trial of adequate length and dose to determine effectiveness. Partial
      responders may require the addition of a second class of medication. Positive
      responders should be maintained on medication for at least 6 months after
      remission of acute PTSD and at least 12 months after remission of chronic PTSD.
      The initial successes of pharmacotherapy for trauma are spurring further research
      and more effective medications can be anticipated in the foreseeable future.

PMID- 11953938
TI  - A developmental and neurobiological approach to early trauma research.
AB  - Basic and clinical research documents associations between stress and a set of
      related psychobiologic perturbations, including dysfunction of the hypothalamic
      pituitary-adrenal axis, alterations in the structure and function of the medial
      temporal lobe, and impairments in explicit memory. Although these associations
      are thought to emerge developmentally, insufficient clinical research elucidates
      the manner in which early trauma relates to these abnormalities. To gain a better
      understanding of relevant processes, we propose the use of a developmental and
      neurobiological approach, where data in animal models are used to inform studies
      in traumatized children who will be followed longitudinally. This approach will
      help clarify how early traumatic events have the capacity to lead to
      psychopathology or a healthy outcome.

PMID- 11953939
TI  - Neurobiology of early life stress: clinical studies.
AB  - A burgeoning number of clinical studies have evaluated the immediate and long
      term neurobiological effects of early developmental stress, eg, child abuse and
      neglect or parental loss, in the past years. This review summarizes and discusses
      the available findings from neuroendocrine (hypothalamic-pituitary-adrenal axis,
      other neuroendocrine axes), neurochemical (catecholamines, serotonin, other
      neurotransmitters), psychophysiological (autonomic function, startle reactivity,
      brain electrical activity) and neuroimaging studies (brain structure, function)
      conducted in children or adults with a history of early life stress, with or
      without psychiatric disorders. Early developmental stress in humans appears to be
      associated with neurobiological alterations that are similar to many findings in
      animal models of early life stress, and likely represent the biological basis of
      an enhanced risk for psychopathology. Clinical studies are now beginning to
      explore potentially differential neurobiological effects of different types of
      early life stress and the existence of critical developmental periods, which may
      be sensitive to the neurobiological effects of specific stressors. In addition,
      the role of a multitude of moderating and mediating factors in the determination
      of individual vulnerability or resilience to the neurobiological effects of early
      life stress should be addressed. Findings from such studies may ultimately help
      to prevent the deleterious neurobiological and psychopathological consequences in
      the unacceptably high number of children exposed to early life stress in modern
      society.

PMID- 11953940
TI  - Assessing the accuracy of high-resolution X-ray computed tomography of primate
      trabecular bone by comparisons with histological sections.
AB  - Different lines of evidence suggest that trabecular bone architecture contains a
      functional signal related to an organism's locomotor behavior. An understanding
      of the interspecific and intraspecific variation in extant nonhuman primate
      trabecular structure is needed to evaluate its usefulness as a tool to
      reconstruct the locomotor habits of extinct primates. High-resolution X-ray
      computed tomography (HRXCT) is a new imaging approach with a resolution in the
      tens of microns that allows nondestructive access to the internal structure of
      bony elements. Previous studies indicate that such resolution is necessary to
      accurately quantify structural parameters of trabecular bone. The primary goal of
      this study was to test the accuracy of HRXCT by comparing stereological
      measurements from HRXCT images and histological thin sections of cancellous bone
      taken from the proximal femur and humerus of baboons. To this end, 11 bone
      samples were scanned on an HRXCT scanner and then thin-sectioned to reveal the
      scanned plane. HRXCT images were thresholded using a modified half-maximum height
      protocol. The stereological measurements included bone volume fraction (BV/TV),
      trabecular number (Tb.N), bone surface to volume ratio (BS/BV), trabecular
      thickness (Tb.Th), and trabecular spacing (Tb.Sp). The measurement errors on the
      HRXCT images were 10.90% for BV/TV, 6.06% for Tb.N, 14.19% for BS/BV, 14.33% for
      Tb.Th, and 7.09% for Tb.Sp, but none of these measurements were significantly
      different from the histological standards (alpha = 0.05). A second goal of this
      study was to examine the influence of thresholding, a necessary step in any
      morphometric study using computed tomography, on the accuracy of the quantitative
      morphometry. Threshold values derived from a modified half-maximum height
      protocol showed that parameters derived from the region of interest (area in
      which stereological measurements were later taken) produced better
      reconstructions of the actual bone structure than threshold values derived from
      more inclusive areas of bone. We conclude that HRXCT can accurately reconstruct
      the complex architecture of trabecular bone, and that thresholding is a
      nontrivial step in trabecular bone studies, with even slight changes in the
      protocol greatly affecting the morphometric data. HRXCT represents a valuable
      analytical tool that should be of interest to a great many researchers in
      physical anthropology because it allows nondestructive access to internal
      morphology, thereby preserving valuable and limited skeletal collections.

PMID- 11953941
TI  - Analysis of tufted capuchin (Cebus apella) courtship and sexual behavior
      repertoire: changes throughout the female cycle and female interindividual
      differences.
AB  - Sexual solicitations and initiative (proceptivity, sensu Beach [1976] Horm Behav
      7:105-138) are important components of the sexuality of females of many primate
      species. In the tufted capuchin (Cebus apella), female proceptivity characterizes
      the species' mating system. In study 1, we defined and discussed 20 behavioral
      patterns based on the observation of 6 females and 5 males living in two social
      groups. In study 2, each behavior, including mounting activity, was
      quantitatively assessed during the periovulatory and nonperiovulatory cycle
      phases of 4 females, detected on the basis of urinary progestin levels (N = 20
      ovulatory cycles, 5 for each female); moreover, we monitored changes in females'
      social interactions (agonism, grooming activity, and play). Nine of the behaviors
      typically used by the female during courtship and in sexual interactions showed a
      dramatic increase during the periovulatory phase. Though males mounted females at
      an apparently higher rate during the periovulatory than the nonperiovulatory
      phase, the difference was not significant. However, when adult male mounting is
      separated into those which occur within play and nonplay contexts, there is a
      significant periovulatory phase effect for mounts not associated with play.
      Females groomed adult males at the same rate throughout the cycle. Agonism and
      play did not show any phase effect; however, females' avoidance of adult males
      significantly increased during the periovulatory phase. Finally, each female made
      a statistically different use of the behavioral repertoire by performing some
      behaviors more than others. This variability among females during courtship calls
      for further research into whether it affects mating success.

PMID- 11953942
TI  - Male orangutan subadulthood: a new twist on the relationship between chronic
      stress and developmental arrest.
AB  - Both in the wild and in captivity, a marked and enduring arrest of secondary
      sexual developmental occurs in some male orangutans (Pongo pygmaeus) (Kingsley
      [1982] The Orang-Utan: Its Biology and Conservation, The Hague: Junk; Utami
      [2000]). Researchers have hypothesized that chronic stress, perhaps related to
      aggression from mature males, causes endocrine changes altering growth and
      maturation rates in these males (Maple [1980] Orangutan Behavior, New York: Van
      Nostrand Reinhold; Graham [1988] Orangutan Biology, Oxford: Oxford University
      Press). In this study, urine samples were collected over a 3-year period from 23
      captive male orangutans to test the hypothesis that developmentally arrested male
      orangutans have an endocrine profile consistent with chronic stress. Three study
      males were juveniles, seven were arrested adolescents, six were developing
      adolescents, and seven were mature adults. Morning samples were analyzed by
      radioimmunoassay for levels of the stress hormones cortisol and prolactin, and
      group hormone profiles were compared by analysis of variance. Results indicate
      that developing adolescent male orangutans have a significantly higher stress
      hormone profile than juvenile, developmentally arrested adolescent, or adult
      males. These results imply that the arrest of secondary sexual development in
      some male orangutans is not stress-induced, but instead perhaps an adaptation for
      stress avoidance during the adolescent or "subadult" period. These data, together
      with previously reported data on levels of gonadotropins, testicular steroids,
      and growth-related hormones, define endocrine profiles associated with
      alternative reproductive strategies for males with and males without secondary
      sexual features (Maggioncalda et al. [1999], [2000].

PMID- 11953944
TI  - Morphological variation within a macaque hybrid zone.
AB  - A hybrid zone exists between Macaca tonkeana and Macaca hecki (Primates:
      Cercopithecidae), centered along the Tawaeli-Toboli road in the narrow isthmus
      that connects North and Central Sulawesi, Indonesia. The current study
      demonstrates morphological substructure from north to south across the hybrid
      zone. Macaques to the northwest of the Tawaeli-Toboli road more closely resemble
      M. hecki, and macaques to the southeast of the road resemble M. tonkeana. While
      morphology shifted for both males and females over a distance of 1,500-2,000 m,
      adult males were significantly more M. tonkeana-like across the morphological
      gradient. This suggests that in the study area, males of M. tonkeana-like
      morphology are dispersing into hybrid groups at the expense of M. hecki-like
      males. A permutation analysis of diagnostic character states indicated that
      associations existed among several morphological traits. This could be due to the
      operation of one or several nonexclusive evolutionary processes, including recent
      secondary contact, pleiotropic effects, physical linkage of loci, natural
      selection against hybrids, the influx of parental types, or assortative mating.
      Continued environmental perturbation associated with the Tawaeli-Toboli road is
      likely to be a significant factor in the future of the M. tonkeana/M. hecki
      hybrid interaction.

PMID- 11953943
TI  - Unequal contributions of male and female gene pools from parental populations in
      the African descendants of the city of Melo, Uruguay.
AB  - In admixed populations, genetic contributions from males and females of specific
      parental populations can be of different proportions due to past directional
      mating during the process of genetic admixture. In this research paper, we
      provide evidence of such male- and female-specific differential admixture
      components of African, European, and American Indian origin in an admixed
      population from the city of Melo, in the northeastern region of Uruguay. From
      data on 11 autosomal markers from a sample of 41 individuals of mixed African
      descent, we estimated 47% African, 38% European, and 15% Amerindian
      contributions. In contrast, 6 mtDNA site-specific polymorphic markers showed that
      the mtDNA genome of these individuals was 52% African, 19% European, and 29%
      Amerindian, while from 3 Y-specific polymorphic sites, we estimated 30% African,
      64% European, and 6% Amerindian contributions. We argue that this heterogeneity
      of admixture estimates results from disproportionate unions of European males
      with African and American Indian females from which this mixed African population
      was formed. Also, we argue that the asymmetry of the admixture estimates from the
      three sets of markers (autosomal, mtDNA, and Y-linked) is a result of the changes
      in the direction of mating during the history of the population. Implications of
      such evidence of directional mating are discussed, indicating the need of further
      demographic data for a quantitative assessment of the impact of directional
      mating on genetic structure of admixed populations.

PMID- 11953945
TI  - Ontogenetic study of the skull in modern humans and the common chimpanzees:
      neotenic hypothesis reconsidered with a tridimensional Procrustes analysis.
AB  - Heterochronic studies compare ontogenetic trajectories of an organ in different
      species: here, the skulls of common chimpanzees and modern humans. A growth
      trajectory requires three parameters: size, shape, and ontogenetic age. One of
      the great advantages of the Procrustes method is the precise definition of size
      and shape for whole organs such as the skull. The estimated ontogenetic age
      (dental stages) is added to the plot to give a graphical representation to
      compare growth trajectories. We used the skulls of 41 Homo sapiens and 50 Pan
      troglodytes at various stages of growth. The Procrustes superimposition of all
      specimens was completed by statistical procedures (principal component analysis,
      multivariate regression, and discriminant function) to calculate separately size
      related shape changes (allometry common to chimpanzees and humans), and
      interspecific shape differences (discriminant function). The results confirm the
      neotenic theory of the human skull (sensu Gould [1977] Ontogeny and Phylogeny,
      Cambridge: Harvard University Press; Alberch et al. [1979] Paleobiology 5:296
      317), but modify it slightly. Human growth is clearly retarded in terms of both
      the magnitude of changes (size-shape covariation) and shape alone (size-shape
      dissociation) with respect to the chimpanzees. At the end of growth, the adult
      skull in humans reaches an allometric shape (size-related shape) which is
      equivalent to that of juvenile chimpanzees with no permanent teeth, and a size
      which is equivalent to that of adult chimpanzees. Our results show that human
      neoteny involves not only shape retardation (paedomorphosis), but also changes in
      relative growth velocity. Before the eruption of the first molar, human growth is
      accelerated, and then strongly decelerated, relative to the growth of the
      chimpanzee as a reference. This entails a complex process, which explains why
      these species reach the same overall (i.e., brain + face) size in adult stage.
      The neotenic traits seem to concern primarily the function of encephalization,
      but less so other parts of the skull. Our results, based on the discriminant
      function, reveal that additional structural traits (corresponding to the
      nonallometric part of the shape which is specific to humans) are rather situated
      in the other part of the skull. They mainly concern the equilibrium of the head
      related to bipedalism, and the respiratory and masticatory functions. Thus, the
      reduced prognathism, the flexed cranial base (forward position of the foramen
      magnum which is brought closer to the palate), the reduced anterior portion of
      the face, the reduced glabella, and the prominent nose mainly correspond to
      functional innovations which have nothing to do with a neotenic process in human
      evolution. The statistical analysis used here gives us the possibility to point
      out that some traits, which have been classically described as paedomorphic
      because they superficially resemble juvenile traits, are in reality independent
      of growth.

PMID- 11953947
TI  - Serum insulin-like growth factor-I, insulin-like growth factor binding protein-3,
      and the pubertal growth spurt in the female rhesus monkey.
AB  - While there is good evidence suggesting IGF-I links to pubertal development and
      crown-rump length growth among rhesus monkeys, linkages between IGF-I and other
      measures of morphological growth have not been established. In this study, the
      pubertal growth spurt in a number of morphological characteristics of female
      rhesus monkeys is related to serum endocrine status of insulin-like growth factor
      I (IGF-I) and its binding protein, insulin-like growth factor binding protein-3
      (IGFBP-3), to test the hypothesis that elevations in IGF-I and IGFBP-3 coincide
      with the time of greatest growth rate of different morphological characteristics.
      A longitudinal study of pubertal growth among four female rhesus monkeys was
      carried out across a 3-year period. Morphometric measurements included weight,
      crown-rump length, foot-length, and skinfolds at five sites (biceps, triceps,
      abdominal, subscapular, and suprailiac). These measures were taken as being
      representative of total mass, skeletal growth of the trunk and head, limb length,
      and body fatness, respectively. Measurements were carried out as closely as
      possible to 3-monthly, with interpolations being performed to standardise the
      data to exactly 3-monthly intervals for all individuals. Blood samples were taken
      at time of morphometry. Elevations in serum IGF-I and IGFBP-3 took place in a
      manner similar to that of humans, and across the period associated with onset of
      puberty. Mean 3-monthly gain in crown-rump length and foot length showed
      significant peaks across the measurement period, while mean 3-monthly gains in
      weight and sum of five skinfolds did not. Greatest foot length gain occurred on
      average between 3-3.5 years of age, while crown-rump length gain was greatest
      between 3.75-4 years of age. Periods of greatest gain in crown-rump length and
      foot length took place across the period of elevated serum IGF-I levels, which
      was between 3-4.5 years of age. Significant elevations in IGF-I and IGFBP-3 were
      not coincident with greatest gains in foot length or crown-rump length. Thus the
      hypothesis does not hold true for the two measures showing significant peaks in 3
      monthly gain across the measurement period. The nature of the endocrine impact on
      macaque morphology remains unclear, although this may be fundamental to the
      understanding of the variation in the pubertal growth spurt and its influence on
      morphology at maturity both within and across primate species.

PMID- 11953948
TI  - Identifying metameric variation in extant hominoid and fossil hominid mandibular
      molars.
AB  - Landmark data were collected from cross sections and occlusal images of
      mandibular molar crowns, and Euclidean distance matrix analysis (EDMA) was used
      to identify metameric morphological variation between the first and second
      mandibular molars of living taxa: Gorilla gorilla (n = 30), Pan troglodytes (n =
      34), and Homo sapiens (n = 26). Two patterns of metameric variation were
      identified, one unique to humans and the other shared by chimpanzees and
      gorillas. In order to assess the utility of this type of analysis for the
      interpretation of the hominid fossil record, 19 mandibular molars from
      Sterkfontein Member 4, South Africa, were examined. The pattern of metameric
      variation of the Sterkfontein molars resembled that of the African great apes,
      and differed from the modern human pattern. These results demonstrate that data
      on metameric variation may provide information regarding function or
      developmental processes previously indiscernible from fossil material.

PMID- 11953946
TI  - Genetic relationship of Chinese ethnic populations revealed by mtDNA sequence
      diversity.
AB  - The origin and demographic history of the ethnic populations of China have not
      been clearly resolved. In this study, we examined the hypervariable segment I
      sequences (HVSI) of the mitochondrial DNA control region in 372 individuals from
      nine Chinese populations and one northern Thai population. A relatively high
      percentage of individuals was found to share sequences with those from other
      populations of the same ethnogenesis. In general, the populations of southern or
      Pai-Yuei tribal origin showed high haplotype diversity and nucleotide diversity
      compared with the populations of northern or Di-Qiang tribal origin. Mismatch
      distributions from these populations showed concordant features. All except the
      northern groups Nu, Lisu, Tibetan, and Mongolian showed typical signatures of
      ancient population expansions in the mismatch distributions and neutrality tests.
      Episodes of extreme size reduction in the past are one of the likely explanations
      for the absence of evidence of expansion in northern populations. Small sample
      sizes as well as samples from isolated subpopulations contributed to the bumpy
      mismatch distributions observed. Phylogenetic analysis and haplotype sharing
      among populations suggest that current mtDNA variation in these ethnic
      populations could reveal their ethnohistory to some extent, but in general,
      linguistic and geographic classifications of the populations did not agree well
      with classification by mtDNA variation.

PMID- 11953958
TI  - Urgent care and tight control of rheumatoid arthritis as in diabetes and
      hypertension: better treatments but a shortage of rheumatologists.

PMID- 11953959
TI  - Plasticity of hematopoietic stem cells: enough to induce tolerance and repair
      tissue?

PMID- 11953960
TI  - DNA microarrays: boundless technology or bound by technology? Guidelines for
      studies using microarray technology.

PMID- 11953961
TI  - Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis?

PMID- 11953962
TI  - Gene expression profiles: creating new perspectives in arthritis research.

PMID- 11953963
TI  - Proteomics technologies for the study of autoimmune disease.

PMID- 11953964
TI  - Delay to institution of therapy and induction of remission using single-drug or
      combination-disease-modifying antirheumatic drug therapy in early rheumatoid
      arthritis.
AB  - OBJECTIVE: To study the impacts of 1) the delay from the onset of symptoms to the
      institution of disease-modifying antirheumatic drug (DMARD) therapy, 2) two
      treatment strategies (treatment with a combination of DMARDs or with a single
      drug), and 3) the presence of HLA-DRB1 alleles (shared epitope) on the prediction
      of disease remission after 2 years in patients with early rheumatoid arthritis
      (RA). METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy)
      trial, 195 patients with recent-onset RA (median duration 6 months) were randomly
      assigned to receive either 1) a combination of DMARDs (sulfasalazine,
      methotrexate, hydroxychloroquine, and prednisolone) or 2) a single DMARD with or
      without prednisolone. The presence of a shared epitope was tested for in 165 of
      the 178 patients completing the study. The additional variables of age, sex,
      presence of rheumatoid factor, number of fulfilled American College of
      Rheumatology criteria for the classification of RA, and length of delay from
      onset of symptoms to institution of therapy were entered into a logistic
      regression model to determine the significant predictors for remission at 2
      years. RESULTS: The delay to therapy (cut point of 4 months) was the only
      significant predictor for remission in patients treated using the single-DMARD
      strategy, while no variable was a significant predictor for remission in those
      treated using the combination-DMARD strategy. The frequency of achieving
      remission in the combination-DMARD group after 2 years was similar in patients
      with short (0-4 months) and long (>4 months) delay periods (11 of 26 patients and
      22 of 53 patients, respectively [approximately 42% in each group]), while the
      corresponding frequencies in the single-DMARD group were 8 of 23 patients (35%)
      and 7 of 63 patients (11%) (P = 0.021). The presence of a shared epitope was not
      related to the induction of remission. CONCLUSION: The delay of a few months from
      the onset of symptoms to institution of therapy decreases the ability of the
      traditional single-drug strategy to induce remission in early RA.

PMID- 11953965
TI  - Early and aggressive treatment of rheumatoid arthritis patients affects the
      association of HLA class II antigens with progression of joint damage.
AB  - OBJECTIVE: The presence of certain HLA class II antigens is strongly associated
      with the progression of joint destruction in rheumatoid arthritis (RA). Such
      antigens may be more effective than other class II antigens in inducing the
      formation of autoreactive T cells after presentation of (auto)antigens. We
      investigated whether early and aggressive treatment with disease-modifying
      antirheumatic drugs could modify this relationship. METHODS: We analyzed data
      from 2 studies of patients with early RA treated according to different
      strategies. The first study consisted of 2 cohorts, one (n = 109; median disease
      duration before treatment 4 months) was treated according to the pyramid strategy
      (initial nonsteroidal antiinflammatory drugs, followed by chloroquine [CQ] or
      sulfasalazine [SSZ] when necessary), and the other (n = 97; median disease
      duration before treatment 2 weeks) was immediately treated with CQ or SSZ. The
      second study comprised 155 patients (median disease duration 4 months) from the
      Combinatietherapie Bij Reumatoide Artritis (COBRA) trial, in which patients were
      randomly assigned to combination treatment with step-down prednisolone,
      methotrexate (MTX), and SSZ (n = 76) or with SSZ alone (n = 79). Prednisolone and
      MTX dosages were tapered and stopped after 28 and 40 weeks, respectively. The
      extent of joint damage was measured by the modified Sharp method. RESULTS: In the
      pyramid treatment cohort, the median increase in Sharp score after 2 years was 12
      in patients positive for the shared epitope (SE) and 1 in SE- patients. In the
      immediate treatment cohort, the median increase was 3 in SE+ patients and 2 in SE
      patients. In the SSZ group of the COBRA study, the median increase in Sharp
      score after 1 year was 11 in DR4+ patients and 3 in DR4- patients. In the
      combination treatment group, the median increase was 4 in DR4+ patients and 2 in
      DR4- patients. Significance was confirmed by multiple regression using log
      transformed scores. CONCLUSION: Early and aggressive antirheumatic drug treatment
      affects the association of HLA class II alleles with progression of joint damage
      in RA.

PMID- 11953966
TI  - Rheumatoid factor is the major predictor of increasing severity of radiographic
      erosions in rheumatoid arthritis: results from the Norfolk Arthritis Register
      Study, a large inception cohort.
AB  - OBJECTIVE: To identify the relative contributions of clinical and laboratory
      variables, determined at baseline, in predicting the deterioration of
      radiographic damage 5 years after presentation in patients with inflammatory
      polyarthritis. METHODS: Data from 439 subjects who sought primary care for
      inflammatory polyarthritis were analyzed. All subjects had paired radiographs, of
      which the first was obtained within 24 months of presentation and the second at 5
      years after presentation. The contribution of baseline clinical and laboratory
      variables in predicting the degree of radiologic severity as judged by the Larsen
      score was assessed at both time points. Additionally, the role of these factors
      in predicting change after adjustment for baseline severity was also measured.
      RESULTS: By 5 years, 49% of subjects had evidence of erosions. The median Larsen
      score on the first film was 2 (interquartile range [IQR] 0-10) and the median
      score on the followup film was 7 (IQR 1-25). These corresponded to a median
      deterioration of 3 (IQR 0-14) in all subjects, whereas those subjects with
      evidence of erosions at first film showed a median deterioration of 15 (IQR 6-29)
      on followup. The rheumatoid factor (RF) status, C-reactive protein levels, the
      presence of nodules, and number of swollen joints at baseline were all predictive
      of radiographic severity at first film. Not surprisingly, the baseline
      radiographic score was a predictor of severity of deterioration. However, after
      adjusting for baseline severity, a high titer of RF (>1:160) was also an
      independent predictor of deterioration over 5 years: individuals with an initial
      RF at that level had a progression in their Larsen score that was 2.3 times (95%
      confidence interval 1.7-3.2) higher than that in the RF-negative individuals.
      Apart from this, only age had an independent effect, after adjusting for baseline
      severity, in predicting increasing radiographic joint damage. CONCLUSION: High
      titer RF is an important variable in predicting continuing severity of
      radiographic damage during the first 5 years after presentation with inflammatory
      polyarthritis.

PMID- 11953968
TI  - Reshaping the shared epitope hypothesis: HLA-associated risk for rheumatoid
      arthritis is encoded by amino acid substitutions at positions 67-74 of the HLA
      DRB1 molecule.
AB  - OBJECTIVE: To further analyze the association of HLA-DRB1 alleles with disease
      susceptibility in recent-onset rheumatoid arthritis (RA). METHODS: One hundred
      sixty-seven Caucasian RA patients and 166 healthy controls were typed for HLA
      DRB1. RESULTS: The association of susceptibility to RA with the group of alleles
      encoding the shared epitope susceptibility sequences (SESSs) was confirmed in
      recent-onset RA. Among non-SESS alleles, DRB1*07, *1201, *1301, and *1501 showed
      significant protective effects. Even after correction for the influence of SESS
      alleles, significant independent protective effects of DRB1 alleles were
      observed. Protective alleles shared a third hypervariable region motif.
      Independent homozygosity effects were observed both for susceptibility and for
      protective alleles. CONCLUSION: Nonsusceptibility alleles differ significantly
      with regard to RA risk. Protective alleles show clear homology at positions 67
      74, often encoding isoleucine at position 67 or aspartic acid at position 70.
      Susceptibility and protective alleles both show homozygosity effects. Based on
      these results and on data reported in the literature, in order to incorporate the
      finding of differential risks among nonsusceptibility alleles, we propose to
      reshape the shared epitope hypothesis as follows: HLA-associated risk for RA is
      encoded by amino acid substitutions at positions 67-74 of the HLA-DRB1 molecule.

PMID- 11953967
TI  - Determination of the minimal clinically important difference in rheumatoid
      arthritis joint damage of the Sharp/van der Heijde and Larsen/Scott scoring
      methods by clinical experts and comparison with the smallest detectable
      difference.
AB  - OBJECTIVE: To assess the minimal clinically important difference (MCID) in joint
      damage on hand and foot radiographs of patients with early rheumatoid arthritis
      (RA) as assessed with the Sharp/van der Heijde and Larsen/Scott methods, and to
      study how the smallest detectable difference (SDD) relates to the MCID for each
      method. METHODS: The judgments of an international panel of experts on the
      clinical relevance of progression of joint damage as seen on sets of radiographs
      obtained at 1-year intervals in 4 clinical settings (early versus late RA and
      mild versus high disease activity) were used as the external criterion, which was
      compared with the progression scores as determined by the 2 scoring methods.
      Progression scores with the highest combined sensitivity and specificity for
      detecting clinically relevant progression represented the MCID. Subsequently, the
      sensitivity and specificity of the scoring methods were determined when using the
      SDD as the threshold for relevant progression, and these were compared with the
      sensitivity and specificity of the MCID. RESULTS: The panel judged changes in
      joint damage around the level of the SDD (5.0) of the Sharp/van der Heijde method
      as minimal clinically important, resulting in satisfactory sensitivity (mean 79%)
      and specificity (mean 84%) for detecting clinically important progression in the
      4 clinical settings when using the SDD as the threshold value. The MCID (mean
      2.3) of the Larsen/Scott method was much smaller than its SDD (5.8), and the
      sensitivity for detecting clinically important progression by applying the SDD as
      threshold was consequently low (mean 51%), accompanied by high specificity (mean
      99%). CONCLUSION: This study suggests that the SDD of the Sharp/van der Heijde
      method can be used as the MCID, i.e., as the threshold level for individual
      response criteria. The SDD of the Larsen/Scott method, however, turned out to be
      too insensitive to use as the threshold for individual clinically relevant
      change.

PMID- 11953969
TI  - Interaction between heat-shock protein 73 and HLA-DRB1 alleles associated or not
      with rheumatoid arthritis.
AB  - OBJECTIVE: HLA-DRB1 alleles whose third hypervariable region contains a
      QKRAA/QRRAA/RRRAA motif are associated with rheumatoid arthritis (RA) through
      unknown mechanisms. We previously demonstrated that the QKRAA motif was also
      expressed on the Escherichia coli 40-kd heat-shock protein (HSP) DnaJ. The QKRAA
      motif helps DnaJ bind its partner chaperone, the E coli 70-kd HSP DnaK.
      Furthermore, we observed that in lymphoblastoid cells, Hsp73, the constitutive 70
      kd HSP, associates with HLA-DRB1*0401 (an allele with a QKRAA motif) and targets
      it to lysosomes. In this study, we sought to classify different HLA-DRB1 alleles
      according to their ability to bind Hsp73. METHODS: To evaluate how well different
      HLA-DRB1 alleles could bind Hsp73, we developed a quantitative precipitation
      assay and a direct binding assay. RESULTS: Quantitative precipitation assay from
      total cellular proteins and from lysosomal extracts demonstrated that RA
      associated HLA-DRB1 alleles bound Hsp73 better than did HLA-DRB1 alleles that
      were not associated with RA. HLA-DRB1*0401 was the best Hsp73 binder. These
      findings were confirmed by direct binding assay between purified proteins.
      CONCLUSION: HLA-DRB1*0401 was the best Hsp73 binder among the 8 different HLA
      DRB1 alleles that were tested.

PMID- 11953970
TI  - Local production of complement proteins in rheumatoid arthritis synovium.
AB  - OBJECTIVE: Complement has been repeatedly implicated in the pathogenesis of
      rheumatoid arthritis (RA) based on studies showing reduced levels of native
      complement components and increased levels of complement metabolites in plasma,
      synovial fluid (SF), and synovial tissue (ST) of RA patients. However, there is
      limited information on local production and activation of key factors of the
      complement cascade in RA synovium and their potential modulation by novel
      anticytokine therapies. This study was undertaken to characterize the expression
      of complement proteins and receptors in RA SF and ST. METHODS: Using in situ
      hybridization, immunohistochemistry, and Western blot techniques, we assessed the
      presence of complement proteins C3, factor B (FB), and C5b-9, as well as the
      expression of complement receptors C3aR and C5aR in rheumatoid synovium. C3 and
      FB levels in SF were determined by enzyme-linked immunosorbent assay. Functional
      assessment was performed by examining the effects of soluble tumor necrosis
      factor receptor (sTNFR) p55 gene transfer in the SCID mouse model of RA. RESULTS:
      Complement proteins and receptors could be localized in all RA synovial
      specimens, whereas in osteoarthritis (OA) synovium, only a few, single cells
      expressed complement proteins and receptors. No differences were noted in the
      concentration of C3 between RA and OA in SF; however, FB levels were markedly
      reduced in RA versus OA SF. In RA synovium, in contrast to OA synovium, local
      expression of complement factor and complement receptor messenger RNA was found
      throughout the various ST compartments, suggesting that activation of the
      complement cascade occurs in all parts of the rheumatoid synovium. Moreover, C5aR
      expression was up-regulated following overexpression of sTNFR p55 by adenovirus
      based gene transfer. CONCLUSION: In summary, local complement production and
      activation may play an important role in RA, and specific modulation and
      inhibition of local complement production could be an attractive therapeutic
      target for RA.

PMID- 11953971
TI  - Genome scan for quantity of hand osteoarthritis: the Framingham Study.
AB  - OBJECTIVE: To search for markers linked to quantity of radiographic hand
      osteoarthritis (OA) in the Framingham Heart Study. METHODS: The sample included
      684 original cohort members and 793 offspring in 296 pedigrees. Radiographic OA
      features evaluated included the Kellgren/Lawrence (K/L) score, osteophytes, and
      joint space narrowing (0-3 scale). Four quantitative phenotypes were computed
      from these measurements: sum of K/L scores across hand joints, sum of osteophyte
      scores, sum of joint space narrowing scores, and proportion of affected joints.
      Prior to linkage analysis, these phenotypes were adjusted for age using a linear
      regression analysis from which standardized residuals were computed. The
      regression analysis was performed separately for each sex and each generation.
      The variance component model (SOLAR) was then applied to the normalized scores of
      the residuals. RESULTS: The average age was 62 years for the original cohort and
      54 years for the offspring. Fifty percent of the original cohort and 30% of their
      offspring had at least 1 affected joint (K/L score >or=2). Heritability ranged
      from 28% (proportion of joints affected with OA) to 34% (sum of K/L scores).
      Eight chromosomal regions indicated suggestive linkage (multipoint logarithm of
      odds [LOD] score >1.5) for at least 1 phenotype; LOD scores were highest for
      joint space narrowing, with a multipoint LOD score = 2.96 on chromosome 1p at
      D1S1665. Chromosomes 7, 9, 13, and 19 indicated consistent LOD score elevation
      for multiple OA phenotypes. CONCLUSION: There are several chromosomes that may
      harbor OA susceptibility genes. Further investigation of these regions using
      larger studies and finer maps will be important to confirm linkage.

PMID- 11953972
TI  - Acidic cysteine endoproteinase cathepsin K in the degeneration of the superficial
      articular hyaline cartilage in osteoarthritis.
AB  - OBJECTIVE: To measure cartilage pH in patients with osteoarthritis (OA) and to
      analyze the presence of cathepsin K, the recently discovered acidic
      endoproteinase, in phenotypically altered chondrocytes. METHODS: Intraoperative
      measurements of the pH of clinically normal, fibrillated, superficially fissured,
      and deeply fissured cartilage surfaces (grades 0-3, respectively) in OA patients
      undergoing primary hip replacement surgery were performed with the use of a sting
      electrode sterilized with microbicidic plasma. Fluorescent pH probes were used
      for in situ assessment of cartilage matrix pH. Cathepsin K was assessed using
      quantitative reverse transcriptase-polymerase chain reaction and
      immunohistochemistry methods. RESULTS: The pH of grade 0 cartilage surfaces was
      7.1 +/- 0.4 (mean +/- SD), compared with 6.2 +/- 0.9 (P < 0.05), 5.7 +/- 1.0 (P <
      0.001), and 5.5 +/- 1.0 (P < 0.001) for grades 1-3 cartilage surfaces,
      respectively. Fluorescent pH probes and acid-dependent autocatalytic conversion
      of cathepsin K into its active, low molecular weight form in cartilage confirmed
      these findings. Cathepsin K messenger RNA levels increased in relation to the
      severity of OA, and the number of cathepsin K-containing chondrocytes increased
      from a mean +/- SD of 12 +/- 3 in grade 0 cartilage surfaces to 47 +/- 7, 50 +/-
      6, and 100 +/- 12 in grades 1-3 cartilage surfaces, respectively (P < 0.001 for
      all comparisons). CONCLUSION: Acid-activated, but pharmacologically inhibitable,
      cathepsin K is induced in phenotypically altered chondrocytes in OA. The findings
      suggest that cathepsin K, rather than neutral matrix metalloproteinases, degrades
      the superficial gliding surfaces of the articular hyaline cartilage in OA.

PMID- 11953973
TI  - The modulation of matrix metalloproteinase and ADAM gene expression in human
      chondrocytes by interleukin-1 and oncostatin M: a time-course study using real
      time quantitative reverse transcription-polymerase chain reaction.
AB  - OBJECTIVE: Previous studies have reported elevated levels of interleukin-1 (IL-1)
      and oncostatin M (OSM) in rheumatoid joints, as well as the synergistic
      degradation of human articular cartilage by this cytokine combination. The
      present study was undertaken to investigate the ability of IL-1 and OSM to
      modulate gene expression of matrix metalloproteinase (MMP), ADAM, and ADAM-TS
      (ADAM with thrombospondin motifs) family members in human chondrocytes. METHODS:
      T/C28a4 human chondrocytes were stimulated for 2-48 hours with IL-1 and/or OSM.
      Total RNA was harvested, reverse transcribed, and assessed by real-time
      polymerase chain reaction for the expression of various MMP, ADAM, and ADAM-TS
      messenger RNAs (mRNA). Results were normalized to 18S ribosomal RNA. RESULTS: IL
      1 and OSM synergized to markedly induce the expression of the collagenases MMP-1,
      MMP-8, and MMP-13 as well as MMP-3, an activator of proMMPs. Expression of mRNA
      for MMPs 1, 3, and 13 was induced early, whereas that of MMP-8 mRNA occurred
      late. Gene expression of MMP-14, an MMP that degrades collagen and activates
      proMMP-13, was elevated by this combination. IL-1 and OSM also synergized to
      induce gene expression of the aggrecanase ADAM-TS4, but not ADAM-TS5. CONCLUSION:
      These data indicate that the potent cartilage-degrading properties of the
      combination of IL-1 and OSM are potentially mediated by a synergistic induction
      of the aggrecan-degrading enzyme ADAM-TS4 and the collagen-degrading enzymes MMP
      1, MMP-8, MMP-13, and MMP-14, although differences in the magnitude of response
      and in the time course of induction were observed. A role for MMPs 3 and 14 in
      the activation of proMMPs may also be implicated.

PMID- 11953974
TI  - Influence of hypoxia and reoxygenation on cytokine-induced production of
      proinflammatory mediators in articular cartilage.
AB  - OBJECTIVE: Articular cartilage is an avascular tissue that functions at a lower
      oxygen tension than do most tissues. With mobilization, arthritic joints may
      undergo cycles of hypoxia and reoxygenation. The goal of this study was to
      determine the effects of hypoxia and reoxygenation on cytokine-induced nitric
      oxide (NO) and prostaglandin E(2) (PGE(2)) production in articular cartilage.
      METHODS: Porcine cartilage explants were incubated at 37 degrees C for 72 hours
      in either 1% O(2) (hypoxia) or 20% O(2) (normoxia) in media supplemented with
      interleukin-1alpha (IL-1alpha) or tumor necrosis factor alpha (TNFalpha), with or
      without the NO synthase 2 (NOS2) selective inhibitor 1400W. Culture media were
      then removed and replaced with freshly prepared media and incubated for a further
      24 hours in normoxia. RESULTS: NO levels were significantly higher in explants
      supplemented with IL-1alpha and TNFalpha compared with controls, in both hypoxia
      and normoxia. Compared with normoxia, hypoxia decreased IL-1alpha- and TNFalpha
      induced NO production significantly. Reoxygenation of hypoxic explants resulted
      in sustained significant NO production in response to either cytokine. However,
      comparably high levels of NO production were not sustained in explants cultured
      continuously in normoxia. Although IL-1alpha alone did not significantly increase
      PGE(2) production, significant PGE(2) superinduction occurred in cartilage
      stimulated with IL-1alpha and the NOS2 inhibitor 1400W compared with stimulation
      with IL-1alpha alone in hypoxia, but not in normoxia. CONCLUSION: Oxygen tension
      significantly affects cytokine-induced proinflammatory mediator production in
      articular cartilage. Furthermore, hypoxia alters NO mediation of PGE(2)
      production. Hypoxia and reoxygenation can affect cytokine-induced proinflammatory
      mediator production, suggesting that oxygen tension may influence inflammation
      associated with cartilage injury and disease.

PMID- 11953975
TI  - Specific enzymatic treatment of bovine and human articular cartilage:
      implications for integrative cartilage repair.
AB  - OBJECTIVE: Chondrocyte death in articular cartilage wound edges and the
      subsequent lack of matrix-producing cells in the interface area are considered to
      be a major cause of impaired cartilage wound healing and poor integrative
      cartilage repair. This study was undertaken to investigate whether enzymatic
      matrix digestion can be used to stimulate integrative cartilage repair via a
      mechanism of local increase in the amount of vital chondrocytes in cartilage
      wound edges. METHODS: Full-thickness bovine articular cartilage samples were
      cultured in vitro for 14 days in standard medium. Samples were either left
      untreated or treated for 48 hours with 0.3% hyaluronidase or 30 units/ml highly
      purified collagenase VII. Nuclear and cytoplasmic changes were analyzed to
      determine cell viability, and the number of vital chondrocytes in wound edges was
      determined. Subsequently, we investigated whether increased chondrocyte density
      in the lesion edges resulted in better wound healing. Finally, full-thickness
      human tibial plateau cartilage explants were tested with similar enzyme treatment
      protocols to determine the clinical value of our results. RESULTS: In bovine
      explants a rapid onset of chondrocyte death was observed in wound edges in all
      treatment groups. This led to low chondrocyte density in a band of 0-150 microm
      from the lesion edges in untreated and hyaluronidase-treated explants. Treatment
      with 30 units/ml collagenase resulted in a significant increase in chondrocyte
      density in this area. The integration experiments demonstrated improved
      integration of the lesion edges after treatment with collagenase. In human
      articular cartilage an increase in chondrocyte density at the lesion edges could
      also be achieved, but only when proteoglycans were depleted from the wound edges
      prior to collagenase treatment. CONCLUSION: Treatment with highly purified
      collagenase improves integrative cartilage repair, possibly by increasing the
      cell density at cartilage wound edges.

PMID- 11953976
TI  - The influence of patient characteristics, disease variables, and HLA alleles on
      the development of radiographically evident sacroiliitis in juvenile idiopathic
      arthritis.
AB  - OBJECTIVE: To assess the frequency of sacroiliitis and the radiographic and
      clinical outcome in juvenile idiopathic arthritis (JIA) and determine patient
      characteristics, early disease variables, and genetic markers that predict
      development of sacroiliitis. METHODS: We performed a retrospective cohort study
      of 314 (79%) of the 400 JIA patients first admitted to the hospital between 1980
      and 1985. The participants were examined after a median disease duration of 14.9
      years (range 11.7-25.1). Radiographs of the sacroiliac joints, hips, ankles, and
      tarsi were obtained and studied in a blinded manner by 2 radiologists. The
      presence of HLA-DRB1 and DPB1 alleles was determined by genotyping and that of
      HLA-B27 by serologic testing. Variables relating to the onset and course of the
      disease were obtained by chart reviews. RESULTS: Twenty (6%) of the JIA patients
      developed radiographic sacroiliitis according to the New York criteria. In 9
      patients (45%), sacroiliitis had not been demonstrated before the followup
      examination. At followup, spinal flexion (lateral and anterior) was reduced in 70
      75% of patients with sacroiliitis and in 30-35% of those without sacroiliitis.
      Compared with the JIA patients without sacroiliitis, those with sacroiliitis more
      frequently had inflammatory back pain, enthesitis, radiographic changes in the
      hips and calcanei, erosions of any peripheral joint, and uveitis. Predictors of
      sacroiliitis were HLA-B27, absence of DPB1*02, hip joint involvement within the
      first 6 months, and disease onset after age 8 years. The following factors were
      more common among patients in whom sacroiliitis developed than in other JIA
      patients: DRB1*04, male sex, family history of ankylosing spondylitis, psoriasis,
      inflammatory back pain, and enthesitis within the first 6 months. CONCLUSION: In
      the current study, radiographically evident sacroiliitis had developed in 6% of
      JIA patients after a median disease duration of 14.9 years. HLA-B27, absence of
      DPB1*02, late onset of disease, and early hip involvement were predictors of
      sacroiliitis.

PMID- 11953978
TI  - Outcome and prognostic indicators of diffuse proliferative lupus
      glomerulonephritis treated with sequential oral cyclophosphamide and
      azathioprine.
AB  - OBJECTIVE: To study the outcome and prognostic indicators of diffuse
      proliferative glomerulonephritis (DPGN) in patients with systemic lupus
      erythematosus (SLE) treated with sequential oral cyclophosphamide (CYC) and
      azathioprine (AZA). METHODS: SLE patients with biopsy-proven DPGN treated with
      sequential oral CYC and AZA were studied. Those who achieved renal remission at
      12 months were identified, and the clinical predictors of complete remission were
      evaluated by regression analysis. All patients were followed up until a relapse
      of the nephritis or a doubling of the serum creatinine level occurred. The timing
      and risk factors for flares and creatinine doubling were evaluated by Kaplan
      Meier analysis and with the Cox proportional hazards model. RESULTS: We studied
      55 patients (47 women, 8 men; mean +/- SD age at renal biopsy 31.1 +/- 10.4
      years); 25 (46%) had a serum creatinine level >106 micromoles/liter, and 29 (53%)
      had nephrotic syndrome. At 12 months posttreatment, 37 (67%) had complete
      remission and 12 (22%) had partial remission. The initial serum creatinine level
      was an independent predictor of complete remission. Excluding the 4 patients who
      were treatment- resistant or died, 21 patients (41%) had renal flares during a
      median followup of 4 years. The cumulative risk of renal flare was 6% at 1 year,
      21% at 3 years, and 32% at 5 years. The median time to relapse was 43 months. The
      histologic activity score and the mean daily dose of CYC were multivariate
      predictors of renal flare, by Cox regression. At the last followup visit, 9 of 54
      patients (17%) had a doubling of the creatinine level, 6 of whom (11%) underwent
      dialysis. The cumulative risk of creatinine doubling was 8.4% at 5 years and
      18.2% at 10 years. An increasing chronicity index at the time of initial renal
      biopsy was an independent predictor of deterioration in renal function.
      CONCLUSION: Sequential therapy with oral CYC followed by AZA appears to be an
      effective treatment regimen for DPGN in patients with SLE, with 89% of patients
      achieving complete or partial remission at 12 months, 62.8% remaining in
      remission after 5 years, and 81.8% having stable renal function after 10 years.
      Predictors of treatment resistance and relapse include increasing serum
      creatinine level, higher histologic activity scores, and a lower dose of CYC.
      Increasing chronicity indices predict a deterioration of renal function.

PMID- 11953977
TI  - Renal flares are common in patients with severe proliferative lupus nephritis
      treated with pulse immunosuppressive therapy: long-term followup of a cohort of
      145 patients participating in randomized controlled studies.
AB  - OBJECTIVE: Immunosuppressive agents have become the standard of therapy for
      proliferative lupus nephritis, but some patients may relapse after discontinuing
      treatment. We reviewed the cases of renal flares in a cohort of patients who
      participated in 2 randomized controlled clinical trials at the National
      Institutes of Health and explored the prevalence, outcome, and predictive factors
      of renal flares. METHODS: Data were obtained on 145 patients treated with pulse
      cyclophosphamide, pulse methylprednisolone, or the combination of both. Patients
      had not received immunosuppressive therapy for at least 6 months and had
      experienced complete or partial response according to defined criteria. Renal
      flares were classified as either proteinuric or nephritic based on changes in
      urinary protein and sediment. Most patients who experienced a flare received
      additional immunosuppressive therapy. RESULTS: Seventy-three patients had a
      complete response, and 19 had partial response/stabilization. Forty-one of these
      patients (45%) experienced renal flares (nephritic in 33, proteinuric in 8) after
      a mean followup of 117 months; 31 of them received additional immunosuppressive
      therapy. The median time to renal flare was 36 months in the complete responders
      and 18 months in the partial responders. Eleven of the 41 patients (27%)
      progressed to end-stage renal disease (ESRD); 9 had nephritic flares (all severe
      except for 1) and 2 had proteinuric flares (1 in each responder group). Compared
      with patients who had a complete response, those with a partial response were
      more likely to experience a flare, to have a severe nephritic flare, or to
      progress to ESRD. Low C4 at the time of response and African American ethnicity
      were significant independent risk factors for renal flare, by multivariate Cox
      proportional hazards analysis. CONCLUSION: Nephritic flares are common in
      patients with proliferative lupus nephritis, even in those with a complete
      response to therapy, but they do not necessarily result in loss of renal function
      if treated with additional immunosuppressive agents. Renal flares are an
      important feature of the natural history of lupus nephritis and provide an
      opportunity for additional preventive strategies, as well as measures of efficacy
      in future therapeutic trials.

PMID- 11953979
TI  - Long-term followup of patients treated with total lymphoid irradiation for lupus
      nephritis.
AB  - OBJECTIVE: To describe the long-term survival, renal condition, and morbidity
      outcomes in patients who received total lymphoid irradiation (TLI) for the
      treatment of lupus nephritis. METHODS: Twenty-one patients with biopsy-proven,
      diffuse membranoproliferative glomerulonephritis and significant proteinuria of
      >2.5 grams/day received TLI from 1980 to 1987 at Stanford University Medical
      Center. All patients had previously failed to respond to treatment with high-dose
      corticosteroids or therapy with corticosteroids plus immunosuppressive agents
      (azathioprine, cyclophosphamide, or chlorambucil). RESULTS: The mean duration of
      followup since TLI was 10.7 years. Fifteen of 21 patients (71%) remained alive at
      the time of this assessment. Nine of the 21 patients (43%) survived without
      developing end-stage renal disease (ESRD). The probability of long-term survival
      without ESRD and without need for additional immunosuppressive agents after TLI
      was 19% (4 of 21). Factors predicting renal failure at the time of TLI included
      elevated creatinine levels, increased interstitial fibrosis on renal biopsy, and
      increased fractional excretion of immunoglobulin and albumin. Malignancies were
      found in 4 patients, and opportunistic infections occurred in 7 patients.
      CONCLUSION: Overall, patients with lupus nephritis treated with TLI do not appear
      to have better 10-year survival with lower incidence of ESRD compared with
      patients in published series treated with conventional immunosuppressive
      therapies. However, in this series of patients, treatment with conventional
      immunosuppressive therapies had been unsuccessful and given the limited number of
      adverse events and the efficacy seen in some patients, TLI appears to be a
      reasonable therapeutic option for the treatment of severe lupus nephritis among
      patients who fail to respond under standard cytotoxic regimens.

PMID- 11953981
TI  - Defective Fc-dependent processing of immune complexes in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To explore the Fc receptor-dependent handling of immune complexes
      (ICs) by the fixed mononuclear phagocytic systems (MPS) in patients with systemic
      lupus erythematosus (SLE). METHODS: The processing in vivo of soluble model
      (123)I-hepatitis B/ anti-hepatitis B ICs was studied in 12 healthy subjects and
      10 patients with active SLE. ICs that fixed complement poorly were prepared
      specifically in order to explore Fc receptor-dependent clearance mechanisms.
      Clearance kinetics and organ uptake were assessed by computer-aided gamma
      scintigraphy and serial blood sampling. RESULTS: In both patients and controls,
      the main site of IC clearance was the liver; only 2-6% of injected ICs were taken
      up in the spleen. The kinetics of initial IC clearance were similar in both
      groups, but defective hepatic retention of ICs was demonstrated in patients with
      SLE. At 1 hour, hepatic activity in patients had fallen to 56% of maximum,
      compared with 74% in controls (P = 0.0002). Precipitation studies performed on
      serum samples using staphylococcal protein A-Sepharose indicated that antibody
      complexed tracer was released from the liver 20-50 minutes after injection.
      CONCLUSION: These results indicate that Fc-mediated clearance of ICs is defective
      in patients with SLE and suggest that ligation of ICs by Fc receptors is critical
      for their efficient binding and retention by the fixed MPS in the liver.

PMID- 11953982
TI  - Presence of microchimerism in labial salivary glands in systemic sclerosis but
      not in Sjogren's syndrome.
AB  - OBJECTIVE: To determine whether microchimerism can be implicated in Sjogren's
      syndrome (SS) by studying minor salivary glands, one of the targets of the
      disease. METHODS: Labial salivary gland (LSG) biopsy specimens from 16 female
      patients with primary SS and 11 with systemic sclerosis (SSc) (a disease in which
      microchimerism is frequently detected) were analyzed. All 27 women had a history
      of pregnancy with a male baby. Specimens were microdissected, and polymerase
      chain reaction (PCR) was performed using the unique sex-determining region Y gene
      probe. RESULTS: The sensitivity of PCR for detecting male cells in LSG was high;
      the presence of 3 male cells was consistently detected in DNA extracted from a
      normal female LSG specimen to which male DNA had been added, and 1 male cell was
      detected in 50% of specimens analyzed. Male DNA was not found in any of the
      specimens from the 16 SS patients but was detected in 5 (45%) of 11 SSc specimens
      (P = 0.006). No differences in the rate of detection were found between patients
      with diffuse and limited SSc (male DNA detected in 2 of 3 and 3 of 8,
      respectively; P = 0.55) or between patients with and those without secondary SS
      (1 of 6 and 4 of 5, respectively; P = 0.08). CONCLUSION: The results of our study
      strengthen the possibility that microchimerism is implicated in SSc. This is the
      first study to demonstrate the presence of chimeric cells in LSG from 45% of SSc
      patients, independent of the presence of secondary SS. However, microchimerism
      was not detected in LSG from patients with primary SS, suggesting that the
      pathogenesis of the 2 diseases is different.

PMID- 11953980
TI  - Antiphospholipid syndrome: clinical and immunologic manifestations and patterns
      of disease expression in a cohort of 1,000 patients.
AB  - OBJECTIVE: To analyze the clinical and immunologic manifestations of
      antiphospholipid syndrome (APS) in a large cohort of patients and to define
      patterns of disease expression. METHODS: The clinical and serologic features of
      APS (Sapporo preliminary criteria) in 1,000 patients from 13 European countries
      were analyzed using a computerized database. RESULTS: The cohort consisted of 820
      female patients (82.0%) and 180 male patients (18.0%) with a mean +/- SD age of
      42 +/- 14 years at study entry. "Primary" APS was present in 53.1% of the
      patients; APS was associated with systemic lupus erythematosus (SLE) in 36.2%,
      with lupus-like syndrome in 5.0%, and with other diseases in 5.9%. A variety of
      thrombotic manifestations affecting the majority of organs were recorded. A
      catastrophic APS occurred in 0.8% of the patients. Patients with APS associated
      with SLE had more episodes of arthritis and livedo reticularis, and more
      frequently exhibited thrombocytopenia and leukopenia. Female patients had a
      higher frequency of arthritis, livedo reticularis, and migraine. Male patients
      had a higher frequency of myocardial infarction, epilepsy, and arterial
      thrombosis in the lower legs and feet. In 28 patients (2.8%), disease onset
      occurred before age 15; these patients had more episodes of chorea and jugular
      vein thrombosis than the remaining patients. In 127 patients (12.7%), disease
      onset occurred after age 50; most of these patients were men. These patients had
      a higher frequency of stroke and angina pectoris, but a lower frequency of livedo
      reticularis, than the remaining patients. CONCLUSION: APS may affect any organ of
      the body and display a broad spectrum of manifestations. An association with SLE,
      the patient's sex, and the patient's age at disease onset can modify the disease
      expression and define specific subsets of APS.

PMID- 11953983
TI  - Interleukin-1alpha expression in capillaries and major histocompatibility complex
      class I expression in type II muscle fibers from polymyositis and dermatomyositis
      patients: important pathogenic features independent of inflammatory cell clusters
      in muscle tissue.
AB  - OBJECTIVE: To address the hypothesis that endothelial cells and/or muscle fibers
      are primary targets in the disease process by analysis of muscle tissue from
      patients with polymyositis (PM) and dermatomyositis (DM). METHODS: We included
      patients with laboratory signs and clinical symptoms typical of myositis, but
      without detectable infiltration of clusters of inflammatory cells in their muscle
      biopsy samples. An immunohistochemical technique was applied to identify CD3,
      CD68, lymphocyte function-associated antigen 1alpha, CD11b, very late activation
      antigen 4, endothelium 4, interleukin-1alpha (IL-1alpha), intercellular adhesion
      molecule 1, vascular cell adhesion molecule 1, IgG, IgM, IgA, and HLA-A/B/C in
      muscle tissue. Fiber type was defined by ATPase staining. RESULTS: IL-1alpha
      expression was detected in endothelial cells of capillaries to a greater extent
      in patients than in controls, and class I major histocompatibility complex (MHC)
      expression was significantly increased in muscle fibers. We also observed that
      class I MHC expression was mainly confined to type II muscle fibers. CONCLUSION:
      Our findings imply that defined molecular changes of blood vessels and muscle
      fibers are both independent of adjacent inflammatory infiltrates and could thus
      be primary events in the development of myositis. Moreover, both IL-1alpha and
      class I MHC molecules might be important for the development of clinical symptoms
      in PM and DM patients.

PMID- 11953984
TI  - Temporal arteritis and Chlamydia pneumoniae: failure to detect the organism by
      polymerase chain reaction in ninety cases and ninety controls.
AB  - OBJECTIVE: To examine the reported correlation between the presence of Chlamydia
      pneumoniae in temporal artery biopsy specimens and the diagnosis of temporal
      arteritis (TA). METHODS: Among 90 possible cases of TA identified at our
      institution between 1968 and 2000, 79 of the positive biopsy specimens (88%)
      demonstrated giant cells and the other 11 cases (12%) had other histopathologic
      features compatible with TA; by chart review, all 90 patients were confirmed to
      have met the American College of Rheumatology classification criteria for TA.
      Controls had negative temporal artery biopsy specimens during the same 32-year
      time period and their postbiopsy disease courses were not compatible with TA.
      Controls were matched with each case by sex, year of biopsy, and age within 10
      years. The biopsy specimens from all cases and controls were reevaluated and
      readings were confirmed in a masked manner by an experienced eye pathologist.
      Polymerase chain reaction (PCR) analyses for C pneumoniae were performed on the
      180 samples using 2 different sets of PCR primers (which target 2 different
      genes). A primer set targeting the ompA gene (CP1-CP2/CPC-CPD) was used to
      perform a nested PCR, followed by confirmation of the findings with primers
      targeting the 16S ribosomal RNA (rRNA) gene (Cpn90/Cpn91) in a touchdown-enzyme
      time-release PCR. We used positive and negative controls, as well as controls
      made from infected and noninfected HEp-2 cells, suspended in a formalin-fixed,
      paraffin-embedded matrix. RESULTS: Seventy-six percent of the 180 cases and
      controls were women. The mean age of the cases was 72.0 years (range 53-90), and
      that of the controls was 70.4 years (range 51-86). Eighty percent of the control
      samples were obtained by temporal artery biopsy performed within 1 year of the
      biopsies performed on the matched cases. Using the CP1-CP2/CPC-CPD primer set,
      only 1 TA case sample (1% of all case samples) was positive for the ompA gene.
      One control sample was also positive using these primers. With the Cpn90/Cpn91
      primers, none of the cases and none of the controls were positive for the 16S
      rRNA gene. CONCLUSION: The results of this study using sensitive and specific PCR
      analyses do not support a role for C pneumoniae in the pathogenesis of TA.

PMID- 11953985
TI  - A novel mutation in the third extracellular domain of the tumor necrosis factor
      receptor 1 in a Finnish family with autosomal-dominant recurrent fever.
AB  - OBJECTIVE: To investigate the presence of TRAPS (tumor necrosis factor receptor
      associated periodic syndrome), which is a recently defined, dominantly inherited
      autoinflammatory syndrome caused by mutations in the tumor necrosis factor
      receptor superfamily 1A gene (TNFRSF1A, CD120a), in a Finnish family with
      recurrent fever. METHODS: The TNFRSF1A gene was sequenced in both affected and
      unaffected family members. Flow cytometry and enzyme-linked immunosorbent assay
      analyses were used to assess membrane expression and serum levels of the TNFRSF1A
      protein, respectively. RESULTS: A missense mutation in exon 4, located in the
      third extracellular domain of TNFRSF1A and resulting in an amino acid
      substitution (F112I) close to a conserved cysteine, was found in all 4 affected
      family members and in 1 asymptomatic individual. The mutation was clearly
      associated with low levels of soluble TNFRSF1A as well as with the clinical
      symptoms of recurrent fever and abdominal pain. Impaired shedding of TNFRSF1A
      after phorbol myristate acetate stimulation was detected in blood granulocytes
      and monocytes from the 3 adult family members with the mutation, but in the child
      bearing the mutation and showing clinical symptoms of recent onset, the shedding
      defect was less marked. CONCLUSION: TRAPS should be suspected in any patient who
      presents with a history of intermittent fever accompanied by unexplained
      abdominal pain, arthritis, or skin rash, particularly in the presence of a family
      history of such symptoms. Screening for low serum levels of soluble TNFRSF1A
      identifies individuals who are likely to have TNFRSF1A mutations.

PMID- 11953986
TI  - Arthritis in MRL/lpr mice is under the control of multiple gene loci with an
      allelic combination derived from the original inbred strains.
AB  - OBJECTIVE: To clarify the mode of inheritance and the genome origins of arthritis
      in a lupus-prone strain of mice, MRL/MpJ, bearing a Fas deletion mutant gene, lpr
      (MRL/lpr). METHODS: Using non-lupus-prone strains of mice, C3H/HeJ-lpr/lpr
      (C3H/lpr), (MRL/lpr x C3H/lpr)F(1) intercross and MRL/lpr x (MRL/lpr x
      C3H/lpr)F(1) backcross mice were prepared. Arthritis in individual mice was
      analyzed by histopathologic grading, and the genomic DNA of the backcross mice
      was examined by simple sequence-length polymorphism analysis to determine the
      polymorphic microsatellite markers highly associated with arthritis. RESULTS:
      Arthritis-susceptibility loci with significant linkage were mapped between
      D15Mit111 and D15Mit18 (map position 17.8-18.7 cM) on chromosome 15 and between
      D19Mit112 and D19Mit72 (map position 43.0-55.0) on chromosome 19 (logarithm of
      odds scores 3.5 and 4.3, respectively). Three other loci, one mapped to each of
      chromosomes 1, 2, and 7, showed suggestive linkage. Loci homozygous for MRL
      alleles on chromosomes 1 and 19 enhanced arthritis in both sexes, whereas other
      loci on chromosomes 2 and 15 selectively affected males. A locus homozygous for
      MRL alleles on chromosome 7 inhibited arthritis in both sexes. Three of these
      loci were found to originate from an LG/J strain and 1 from an AKR/J strain. Some
      combinations of these loci showed an additive effect in a hierarchical manner on
      the development of arthritis. CONCLUSION: Arthritis in MRL/lpr mice is a complex
      pathologic manifestation resulting from the cumulative effect of multiple gene
      loci with an allelic combination derived from the original inbred strains.

PMID- 11953987
TI  - Evaluation of quantitative trait loci regulating severity of mycobacterial
      adjuvant-induced arthritis in monocongenic and polycongenic rats: identification
      of a new regulatory locus on rat chromosome 10 and evidence of overlap with
      rheumatoid arthritis susceptibility loci.
AB  - OBJECTIVE: To evaluate the regulatory potential of genetic loci controlling
      Mycobacterium butyricum adjuvant-induced arthritis (Mbt-AIA) using mono- and
      polycongenic rats. METHODS: Of 4 quantitative trait loci (QTLs) that regulate Mbt
      AIA, F344 alleles at 3 of these loci, Aia1, Aia2, and Aia3, are associated with
      lower arthritis severity, whereas F344 alleles at Aia4 are associated with
      greater arthritis severity. In this study, we constructed congenic lines by
      transferring 1 or more of the F344 genomic segments containing Aia1, Aia2, and
      Aia3 onto the DA genome. We comparatively evaluated their responses to Mbt-AIA
      with the responses of parental DA and F344 rats. RESULTS: Aia1, encompassing the
      rat major histocompatibility complex, reduced arthritis severity in monocongenic
      rats of both sexes. The arthritis-lowering effects of Aia2 and Aia3 were sex
      influenced and were therefore observed in only males and only females,
      respectively. Polycongenic rats containing F344 genomic regions at Aia1, Aia2,
      and Aia3 developed Mbt-AIA of relatively greater severity than did F344 rats,
      implying that in DA and F344 rats, there could be other Mbt-AIA loci in addition
      to Aia1, Aia2, Aia3, and Aia4. To test the possibility that some of these Mbt-AIA
      regulatory loci may colocalize with other arthritis QTLs, we evaluated Mbt-AIA in
      DA.F344 monocongenic rats containing collagen-induced arthritis QTLs. Cia5 (the
      QTL region on chromosome 10), but not Cia5a, Cia4, or Cia6, also regulated Mbt
      AIA, and was named Aia5. CONCLUSION: F344 genomic regions at Aia1, Aia2, and Aia3
      and the newly identified Aia5 contain genes that reduce Mbt-AIA severity in DA
      rats. These Mbt-AIA-regulatory loci overlap rheumatoid arthritis-susceptibility
      loci in humans.

PMID- 11953988
TI  - Immunogenicity of recombinant type IX collagen in murine collagen-induced
      arthritis.
AB  - OBJECTIVE: Past attempts to isolate type IX collagen (CIX) from cartilage using
      limited proteolysis yielded partially degraded material. Recent application of
      recombinant technology, however, has allowed the preparation of intact native
      CIX. We used the murine collagen-induced arthritis model to characterize the
      immunologic properties of recombinant human CIX (rCIX) produced using a
      baculovirus expression system. METHODS: A panel of B10 congenic mice was
      immunized with rCIX emulsified with Freund's complete adjuvant (CFA). The ability
      of the rCIX to induce tolerance and suppress arthritis was determined by
      administration intravenously or orally before challenge with CII/CFA. RESULTS:
      None of the mice immunized with rCIX developed overt arthritis, although 2 of 5
      HLA-DR1 transgenic mice developed limited digital erythema and swelling.
      Recombinant CIX administered by either route effectively induced suppression of
      arthritis, although the suppression was less pronounced than that induced with
      CII. Immune responses to CIX and CII were specific, suggesting that bystander
      suppression, rather than cross-reactivity with CII, was instrumental in
      suppressing arthritis. CONCLUSION: These data show that CIX down-regulates
      arthritis in mice while having no associated risk of inducing arthritis.

PMID- 11953989
TI  - Expression of osteopontin at sites of bone erosion in a murine experimental
      arthritis model of collagen-induced arthritis: possible involvement of
      osteopontin in bone destruction in arthritis.
AB  - OBJECTIVE: To investigate the involvement of osteopontin (OPN) in bone
      destruction in a murine experimental arthritis model of collagen-induced
      arthritis (CIA). METHODS: The expression of OPN was examined at both the
      messenger RNA (mRNA) and protein levels in various arthritic lesions in mice with
      CIA by in situ hybridization and immunohistochemistry, respectively. In addition,
      the expression of alpha(v)beta3 integrin, a receptor for OPN, the ligation of
      which is thought to be essential for bone resorption by osteoclasts, was examined
      by immunohistochemistry. Plasma concentrations of OPN were measured at different
      time points in the course of CIA by enzyme-linked immunosorbent assay. RESULTS:
      OPN mRNA was detected mainly at sites of bone erosion in arthritic lesions, where
      activated osteoclasts were present; OPN protein was also detected at sites of
      bone erosion. In the arthritic synovium, OPN was predominantly expressed in the
      synovial lining layer, but not in lymphoid aggregates. In addition, alpha(v)beta3
      integrin was detected coincident with OPN at sites of bone erosion (bone-pannus
      junction). Plasma OPN levels were markedly elevated at the time points that
      corresponded to arthritis flares, and higher levels were maintained during the
      progression of arthritis. CONCLUSION: OPN may mediate bone resorption by
      osteoclasts in arthritis through ligation with its receptor, alpha(v)beta3
      integrin. OPN may be a useful therapeutic target molecule in the prevention of
      bone destruction in arthritis.

PMID- 11953990
TI  - Gene transfer of a fibronectin peptide inhibits leukocyte recruitment and
      suppresses inflammation in mouse collagen-induced arthritis.
AB  - OBJECTIVE: Cell adhesion plays an essential role in arthritis by recruiting and
      retaining leukocytes in the joint. Fibronectin, a major extracellular matrix
      component in synovium, plays a central role in cell-cell and cell-matrix
      interactions through ligation of cell surface integrins. The present study was
      designed to determine the effects of gene transfer of a 15-amino acid peptide
      derived from the 33-kd carboxy-terminal cell and heparin-binding domain of
      fibronectin (FN-C/H-II) on established arthritis in mice. METHODS: Plasmid DNA
      encoding a FN-C/H-II minigene under control of the cytomegalovirus promoter was
      injected intravenously into mice with established collagen-induced arthritis, and
      the effects on leukocyte adhesion and recruitment to the joints was determined.
      RESULTS: Following injection, circulating FN-C/H-II could be detected for at
      least 5 days. Treated mice demonstrated a marked reduction in progression of
      arthritis. Not only was disease progression halted, but a significant improvement
      in joint swelling was observed within 2 days of treatment. Leukocyte adhesion and
      recruitment were inhibited by FN-C/H-II, both in vitro and in vivo. Histologic
      evaluation revealed a marked reduction in infiltration of both neutrophils and
      lymphocytes into synovium, persisting for at least 10 days. CONCLUSION: These
      results suggest that antagonism of cell adhesion by soluble fibronectin peptides
      may provide an approach to attenuating chronic arthritis.

PMID- 11953991
TI  - Suppression of collagen-induced arthritis by single administration of poly(lactic
      co-glycolic acid) nanoparticles entrapping type II collagen: a novel treatment
      strategy for induction of oral tolerance.
AB  - OBJECTIVE: Poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer, is a
      carrier for drug delivery systems. This study was undertaken to investigate the
      tolerogenic effect of single administration of PLGA entrapping type II collagen
      (CII) on the development of collagen-induced arthritis (CIA). METHODS: The
      biophysical properties of PLGA nanoparticles entrapping CII (PLGA-CII) were
      investigated by in vitro release testing of CII, immunohistochemistry analysis,
      and electron microscopy. PLGA-CII was fed singly to animals 14 days before
      immunization, and the effect on joint inflammation was assessed. Circulating IgG
      anti-CII antibodies and T cell responses to CII in draining lymph nodes were
      assayed by enzyme-linked immunosorbent assay and (3)H-thymidine incorporation
      assay, respectively. The expression of messenger RNA (mRNA) for transforming
      growth factor beta (TGFbeta) and tumor necrosis factor alpha (TNFalpha) was
      determined by reverse transcriptase-polymerase chain reaction. RESULTS: The in
      vitro release test showed that CII was slowly discharged from PLGA-CII over a
      period of a month. After single administration of PLGA-CII, numerous particles
      approximately 300 nm in size were detectable in Peyer's patches, by electron
      microscopy and immunohistochemical staining for CII, 14 days after the original
      feeding. Mice fed a single dose of PLGA containing 40 microg of CII had
      significantly reduced values for incidence and severity of arthritis, serum IgG
      anti-CII antibodies, and CII-specific T cell proliferation as compared with mice
      fed solvent alone, those fed 6 doses of 20 microg CII alone, and those fed a
      single dose of PLGA alone. PLGA-CII was also able to suppress CIA after disease
      onset. Moreover, PLGA-CII-fed mice showed a higher level of TGFbeta mRNA
      expression in Peyer's patches, but a lower level of TNFalpha mRNA expression in
      draining lymph nodes, compared with the other groups of mice. CONCLUSION: Our
      data show that PLGA may serve as a powerful vehicle to promote the tolerance
      effect of oral CII and that single administration of PLGA-CII may hold promise as
      a new treatment strategy in rheumatoid arthritis.

PMID- 11953992
TI  - Decrease in synovial cellularity and cytokine expression after autologous stem
      cell transplantation in patients with juvenile idiopathic arthritis.

PMID- 11953993
TI  - Evidence of transplacental passage of hydroxychloroquine in humans.

PMID- 11953994
TI  - The R-H polymorphism of FCgamma receptor IIa as a risk factor for systemic lupus
      erythematosus is independent of single-nucleotide polymorphisms in the
      interleukin-10 gene promoter.

PMID- 11953995
TI  - Thromboembolic events after fetal loss in patients with antiphospholipid
      syndrome: comment on the article by Erkan et al.

PMID- 11953997
TI  - Pro-myeloperoxidase, a target antigen for antineutrophil cytoplasm
      autoantibodies: comment on the article by Russell et al.

PMID- 11953998
TI  - Somatization and development of chronic widespread pain: comment on the article
      by McBeth et al and the editorial by Winfield.

PMID- 11954001
TI  - A celebration of rheumatology health professionals: we make a difference.

PMID- 11954000
TI  - Polymerase chain reaction testing for Tropheryma whippelii in unexplained
      isolated cases of arthritis.

PMID- 11954002
TI  - How should we interpret the lower lip biopsy finding in patients investigated for
      Sjogren's syndrome?

PMID- 11954003
TI  - Steroid hormones in lupus pregnancy: in control?

PMID- 11954004
TI  - Decreased aerobic capacity in children with juvenile dermatomyositis.
AB  - OBJECTIVE: To determine whether patients with juvenile dermatomyositis (DM) have
      limited aerobic capacity compared with healthy controls. METHODS: Fourteen
      juvenile DM patients with inactive to moderately active, stable disease (age
      range 7-17 years) and 14 age- and sex-matched controls performed a maximal
      exercise test using a cycle ergometer. Oxygen uptake and power were measured at
      peak exercise (VO(2peak) and W(peak), respectively) and at anaerobic threshold
      (AT and W(AT)). Juvenile DM disease activity and damage were also assessed.
      RESULTS: Patients with juvenile DM had significantly reduced VO(2peak) (19.6 ml
      O(2)/kg/minute in juvenile DM versus 31.1 ml O(2)/kg/minute in controls), peak
      heart rate (166 versus 184 beats per minute), W(peak) (1.6 versus 2.7 watts/kg),
      AT (11.1 versus 18.0 ml O(2)/kg/minute) and W(AT) (0.6 versus 1.4 watts/kg),
      compared to controls (P <or= 0.05 for each). Aerobic exercise parameters
      correlated with physician global disease activity and damage, T1-weighted
      magnetic resonance imaging, and Childhood Myositis Assessment Scale scores (r(s)
      = 0.58 - 0.82, P <or= 0.05). CONCLUSION: Patients with juvenile DM with a range
      of disease activity have a decreased aerobic and work capacity compared to
      healthy children. Aerobic exercise limitation in juvenile DM correlates best with
      measures of disease damage (global damage assessment, T1-weighted magnetic
      resonance imaging, and disease duration). Aerobic exercise testing may be
      valuable in the assessment of physical endurance, and aerobic training may be
      indicated as part of the therapeutic regimen in myositis patients with inactive
      to moderately active, stable disease.

PMID- 11954005
TI  - Health outcomes assessment in community pharmacy practices: a feasibility
      project.
AB  - OBJECTIVES: To evaluate the feasibility and benefit of capturing outcomes data in
      community pharmacy settings, and to characterize the health status, resource use,
      and medication use of patients with musculoskeletal disorders. METHODS: Patients
      (n = 460) with musculoskeletal disorders including osteoarthritis (OA),
      rheumatoid arthritis (RA), and low back pain from 12 community pharmacy sites
      responded to disease-specific questions, the Medical Outcomes Study Short Form-36
      (SF-36) health survey, demographics, and resource use using touch screen computer
      technology. Patients provided information and met with a community pharmacist for
      scheduled visits at baseline, 3, 6, 9, and 12 months. Pharmacists, with the aid
      of the patient-reported information, documented medication use and identified and
      addressed drug therapy problems of the patients at each visit. Baseline results,
      based on descriptive statistics are reported. RESULTS: OA was reported by 71% of
      the patients, 55% reported low back pain, and 19% reported RA. Despite receiving
      a variety of analgesic medications, a majority of the patients reported
      experiencing moderate to severe pain. SF-36 scores of the study population were
      significantly lower than age-adjusted population norms, with arthritis patients
      reporting worse physical health than patients with low back pain. Drug therapy
      problems were identified in 58% of the population, with need for additional drug
      therapy (31%) and adverse drug reactions (18%) being the most common problems
      identified. CONCLUSIONS: Results indicate that routine capture of patient
      reported health outcomes data is feasible in community pharmacy settings using
      touch screen technology.

PMID- 11954006
TI  - The iatrogenic costs of NSAID therapy: a population study.
AB  - OBJECTIVE: To estimate the iatrogenic costs of nonsteroidal antiinflammatory drug
      (NSAID) treatment from the perspective of the Italian National Health Service.
      METHODS: We conducted a retrospective cohort study using the primary and
      secondary care claims data registered in the regional health service database in
      the Friuli-Venezia Giulia (Italy). The study cohort comprised all
      persons(265,114) who received at least one prescription for any NSAID between
      August 1996 and July 1998. The outcomes of interest were the costs of medical
      interventions for upper gastrointestinal disorders following NSAID treatment
      (i.e., prescriptions for gastroprotective drugs, hospitalizations, and outpatient
      diagnostic procedures). RESULTS: The study population received a total of 660,311
      NSAID prescriptions for a cost of 6,587,533 Euros (0.53 euro per treatment day).
      The cost of medical interventions for gastrointestinal events added 58% to the
      cost of NSAID therapy (0.31 euro per NSAID treatment day, up to 64% directly
      attributable to NSAID use). The iatrogenic costs were generated by 12.4% of the
      patients, 77% of whom had a positive history of gastrointestinal disorders and
      82% of whom were older than 50 years. Co-prescriptions for gastroprotective drugs
      accounted for 78.6% of the overall iatrogenic costs. The iatrogenic costs did not
      differ between cyclooxygenase (COX) nonselective and COX-2 preferential drugs
      within strata of age and prior history of gastrointestinal disorders, but were
      significantly higher for the parenteral NSAIDs than the oral or rectal
      formulations. CONCLUSIONS: In Italy, the iatrogenic costs of NSAID therapy add
      58% to the cost of NSAID treatment; most of the cost is generated by co
      prescriptions of gastroprotective drugs to elderly NSAID users or patients with a
      history of gastrointestinal disorders.

PMID- 11954007
TI  - Declines in strength and balance in older adults with chronic knee pain: a 30
      month longitudinal, observational study.
AB  - OBJECTIVES: To document changes in lower extremity strength and balance over a 30
      month period in older adults with chronic knee pain, and to identify
      relationships among these variables that may prove useful in designing a
      subsequent clinical intervention trial. METHODS: This longitudinal, 30-month,
      observational study was designed to examine the association of physical,
      psychological, social, and environmental factors with severity and progression of
      physical disability caused by chronic knee pain. This article will focus on 2
      physical measures: strength and dynamic balance. The participants were a cohort
      of 480 adults 65 years of age or older with chronic knee pain. Measurements
      included: 1) force platform dynamic balance measure of the center of pressure
      excursion during a forward and subsequent backward lean, 2) isokinetic strength
      measures of concentric and eccentric knee flexion and extension, and concentric
      ankle plantar flexion and dorsiflexion, and 3) body mass index and a knee pain
      scale to measure obesity and knee pain, respectively. RESULTS: A maximum
      likelihood analysis revealed an overall significant decline in knee (P < 0.001)
      and ankle (P = 0.012) strength, and balance (P < 0.001) after a 30-month followup
      period. Participants with greater knee strength at baseline had less expected
      decline in balance at followup than their weaker counterparts (4.2% versus 7.7%
      for the 75th versus 25th percentiles of strength; P = 0.023). However, the
      absolute decline in balance over 30 months was similar regardless of baseline
      ankle strength. CONCLUSIONS: Adults age >or=65 years with chronic knee pain
      experience significant declines in balance and lower extremity strength over a 30
      month period. Moreover, greater knee and ankle muscular strength is associated
      with better balance. Previous studies have shown that weight training is
      effective in improving balance in older adults with knee osteoarthritis. Taken
      together, these studies present a strong rationale for incorporating weight
      training into an exercise prescription for older adults with chronic knee pain.

PMID- 11954008
TI  - Descriptions of joint pain by American Indians: comparison of inflammatory and
      noninflammatory arthritis.
AB  - OBJECTIVE: To improve assessment of arthritis joint pain in American Indians by
      describing how symptoms are communicated. METHOD: In-depth interviews were
      conducted with American Indians who experience chronic joint pain (n = 56), to
      elicit descriptions and self-reported ratings of pain, disability, and beliefs
      associated with the pain for affected joints (n = 326). RESULTS: Discrete sets of
      specific verbal descriptions distinguished inflammatory arthritis (n = 20 terms)
      from noninflammatory arthritis (n = 22 terms), and indicated levels of pain
      intensity. An additional set of 14 vague but commonly used verbal descriptors did
      not distinguish the type of joint disease or pain intensity. CONCLUSIONS: Subtle
      pain complaints and vague verbal descriptions, such as "ache," "hurt," and
      "discomfort," may reflect severe pain symptoms, disability, and more serious
      joint disease in American Indian patients. In addition, certain specific sensory
      descriptions used by American Indians suggest inflammatory arthritis and may
      warrant further evaluation.

PMID- 11954009
TI  - Value of laboratory tests in early prediction of rheumatoid arthritis.
AB  - OBJECTIVE: To determine which laboratory test or tests at presentation best
      predicted a diagnosis of rheumatoid arthritis (RA) 2 years later. METHODS: Two
      hundred seventy patients with early arthritis seen in 7 hospitals underwent
      comprehensive evaluations at 6-month intervals for 2 years, when the diagnosis of
      RA was assessed by 5 rheumatologists. The sensitivity and specificity of each
      test at the first visit for discriminating between RA (38%, n = 98) and non-RA
      patients were determined. Optimal cutoffs for continuous tests were derived from
      receiver operating characteristic curves. Sensitivity and specificity of test
      combinations selected by multiple logistic regression were determined. RESULTS:
      IgM rheumatoid factor (RF) by enzyme-linked immunosorbent assay, IgG-antikeratin
      antibody (AKA), and latex test had the strongest associations with RA. These 3
      tests formed the most powerful combination for distinguishing RA from non-RA.
      CONCLUSION: IgM-RF, IgG-AKA, and the latex test are the best laboratory tests for
      discriminating between patients with and without RA. Combining these tests
      slightly improves diagnostic value.

PMID- 11954010
TI  - Erythroblast iron metabolism and serum soluble transferrin receptor values in the
      anemia of rheumatoid arthritis.
AB  - OBJECTIVES: We have investigated in vitro erythroblast iron metabolism in the
      anemia of rheumatoid arthritis (RA). We also have examined the results in
      relation to bone marrow iron status in an attempt to explain the reported
      difference between serum soluble transferrin receptor (sTfR) values in anemia of
      chronic disease (ACD) and iron deficiency anemia (IDA) in patients with RA.
      METHODS: Bone marrow was examined in 29 anemic patients with RA, 9 healthy
      volunteers, and 6 patients with simple IDA. High purity erythroblast fractions
      were prepared from these bone marrow samples. Erythroblast surface TfR expression
      and iron uptake was assessed in vitro using (125)I-transferrin (Tf) and (59)Fe
      Tf, respectively. The efficiency of erythroblast surface TfR function for Tf-iron
      uptake was determined by relating total iron uptake at 4 hours to surface TfR
      number. Serum sTfR values were measured for the RA anemia group, which was
      subdivided as RA-ACD (marrow iron present) or RA-IDA (marrow iron absent) on the
      basis of visible reticuloendothelial (RE) marrow iron stores. RESULTS: High
      purity (87 +/- 5%) erythroblast fractions were obtained from 35 of the 44 marrow
      samples. Erythroblasts obtained from patients with simple IDA showed a
      significant increase in surface TfR expression (P = 0.0003) and Tf-iron uptake (P
      = 0.001). RA anemia also led to a significant increase in erythroblast Tf-iron
      uptake (P = 0.016). This increase was not associated with an increase in surface
      TfR expression (P = 0.5), but was seen to occur as a result of a significant
      increase in the efficiency of surface TfR for Tf-iron uptake (P = 0.027). Within
      the RA anemia group, the increase in erythroblast Tf- iron uptake at 4 hours was
      more evident for RA-IDA (3.96 +/- 1.73 versus 1.66 +/- 0.66; P = 0.03) than for
      RA-ACD (2.69 +/- 1.18 versus 1.66 +/- 0.66; P = 0.057). This additional
      erythroblast response to absent RE iron stores led to a highly significant
      difference in serum sTfR values between RA-IDA and RA-ACD (40.2 +/- 14.0 versus
      23.9 +/- 5.3 nmoles/liter; P = 0.001) CONCLUSIONS: An increase in erythroblast
      surface TfR efficiency for Tf-iron uptake compensates for the low plasma iron
      levels associated with anemia in RA and helps to maintain RA erythroblast iron
      uptake. With adequate RE iron stores, this increased efficiency limits
      intracellular iron deprivation and consequently reduces the need to increase
      surface TfR expression. As a result, serum sTfR levels in RA-ACD remain within
      the normal range. RA erythroblasts, however, are still able to respond to any
      additional worsening of the iron supply caused by absent RE iron stores. This
      additional response causes the highly significant increase in serum sTfR values
      seen between RA-IDA and RA-ACD.

PMID- 11954011
TI  - The prevalence and impact of managed care for persons with rheumatoid arthritis
      in 1994 and 1999.
AB  - OBJECTIVES: To estimate the proportion of persons with rheumatoid arthritis (RA)
      in managed care and fee-for-service settings in 1994 and 1999, to ascertain
      whether there are differences in utilization between persons in the 2 systems of
      care in the 2 years, and to determine whether 1994 managed care status or change
      between 1994 and 1999 in managed care status affects outcomes. METHODS: The
      present study uses data from the University of California, San Francisco RA Panel
      Study, in which 310 patients with RA from a random sample of Northern California
      rheumatologists were interviewed annually between 1994 and 1999 using a
      structured survey instrument. We use linear and logistic regression to compare
      the health care utilization and outcomes of persons in managed care and fee-for
      service after adjusting for differences in demographic and health
      characteristics. RESULTS: The proportion of respondents in managed care increased
      from 60% to 79% between 1994 and 1999, including an increase from 37% to 68%
      among persons eligible for Medicare and an increase from 74% to 92% among persons
      ineligible for Medicare. With the exception of physical therapy visits in 1999,
      patients with RA in managed care did not report significantly different
      utilization of any service for RA than those in fee-for-service in either 1994
      and 1999, including hospital admissions and joint replacement surgery. Managed
      care status in 1994, and change in managed care status between 1994 and 1999,
      were not associated with significantly different outcomes in 1999. CONCLUSION:
      Despite the growth in the proportion of patients with RA in managed care, those
      in managed care did not differ from those in fee-for-service settings in
      utilization or outcomes.

PMID- 11954012
TI  - Laboratory testing in rheumatoid arthritis patients taking disease-modifying
      antirheumatic drugs: clinical evaluation and cost analysis.
AB  - OBJECTIVE: To develop and validate evidence-based recommendations for routine
      laboratory tests in patients with rheumatoid arthritis (RA) receiving traditional
      disease-modifying antirheumatic drugs (DMARDs), and to calculate the monitoring
      costs. METHODS: Outpatient charts of 362 RA patients taking DMARDs were reviewed,
      and all laboratory abnormalities recorded. Recommendations on monitoring DMARD
      therapy were derived and then tested in an independent validation cohort of 231
      patients. Cost analysis was performed using a cost catalog. RESULTS: Laboratory
      abnormalities were seen in 10% of treatment courses; relevant abnormalities were
      seen only during the first 4 months of therapy. Laboratory tests should be
      performed in week 2 and 4, then monthly for the first 4 months of therapy, then 2
      to 4 times per year. These were capable of detecting 98.3% of laboratory
      abnormalities in a timely manner in another RA cohort. Up to 78% of costs can be
      saved when the presented recommendations are compared with those of international
      rheumatology societies. CONCLUSION: Laboratory tests can be reduced substantially
      in patients receiving DMARD therapy. In consequence, costs can decrease
      significantly without oversight of adverse events.

PMID- 11954013
TI  - Risk factors for positive minor salivary gland biopsy findings in Sjogren's
      syndrome and dry mouth patients.
AB  - OBJECTIVE: To investigate risk factors for positive minor salivary gland biopsy
      results in Sjogren's syndrome (SS) and dry mouth patients. METHODS: A total of
      289 patients with dry mouth symptoms were evaluated. Potential risk factors for
      positive minor salivary gland biopsy results (>1 focus of lymphocytes) were
      studied in 2 phases. In phase 1, predictor variable candidates were identified
      for the test study (phase 2). Odds ratios were calculated for predictor
      variables. RESULTS: IgG, IgA, keratoconjunctivitis sicca, and sex, identified as
      the best predictor variables from phase 1 data, were included in a logistic
      regression model using phase 2 data. Only IgG demonstrated association with
      biopsy results (chi(2) = 20.4, P = 0.0001). An elevated IgG level (>1,482 mg/dl)
      had a high specificity (97% and 97%), high positive predictive value (PPV) (97%
      and 97%), but poor sensitivity (40% and 45%) in predicting positive biopsy
      results and SS, respectively. CONCLUSION: Elevated serum IgG levels best
      predicted a positive biopsy result and SS with high PPV and specificities.

PMID- 11954014
TI  - Patients' perceptions of the effects of systemic lupus erythematosus on health,
      function, income, and interpersonal relationships: a comparison with Wegener's
      granulomatosis.
AB  - OBJECTIVE: To describe the patients' perceptions of the effects of systemic lupus
      erythematosus (SLE) and Wegener's granulomatosis (WG) on health, function,
      income, and interpersonal relationships. METHODS: 114 patients with SLE, and 79
      patients with WG completed a self-administered questionnaire. Patients had been
      diagnosed with SLE or WG for a median period of 10 and 5 years, respectively.
      RESULTS: All patients experienced substantial functional morbidity. Two-thirds of
      the patients with SLE or WG reported either a periodic or permanent inability to
      perform daily activities at home and/or at work. Furthermore, SLE as well as WG
      had a considerable impact upon the psychological and social life, affecting their
      happiness and altering relationships. CONCLUSION: Our study demonstrates that SLE
      and WG are associated with substantial medical morbidity resulting in physical
      and occupational disability. SLE has a profound impact on patients' lives,
      similar to that experienced in patients with WG.

PMID- 11954015
TI  - Steroid hormones and disease activity during pregnancy in systemic lupus
      erythematosus.
AB  - OBJECTIVES: To analyze the variation of steroid hormone levels during pregnancy
      in patients with systemic lupus erythematosus (SLE). Moreover, to investigate
      whether, during gestation, there is any relationship between steroid
      concentration and SLE activity. METHODS: Seventeen consecutive pregnant SLE
      patients and 8 matched healthy pregnant controls were studied prospectively.
      Disease activity was evaluated by European Consensus Lupus Activity Measure
      (ECLAM) score modified for pregnancy. The following hormones were evaluated:
      testosterone, 17beta-estradiol (estradiol), cortisol, dehydroepiandrosterone
      sulfate (DHEAS), and progesterone. RESULTS: Disease activity score significantly
      varied during pregnancy and postpartum (P< 0.05), being decreased in the third
      trimester and increased in the second trimester and postpartum. Serum levels of
      all steroids varied significantly during pregnancy and the postpartum period both
      in patients and in healthy subjects. In SLE patients, estradiol, progesterone,
      and DHEAS concentrations were found to be significantly reduced compared with
      controls. Serum level profiles of estradiol and progesterone were different from
      those observed in controls. No differences in the steroid levels were observed
      between patients taking prednisone <or=5 mg/day or >5 mg/day, apart from
      cortisol, which was, as expected, lower in the latter group. CONCLUSIONS: The
      major hormonal alteration observed during pregnancy in SLE patients was an
      unexpected lack of estrogen serum level increase, and, to a lesser extent,
      progesterone serum level increase, during the second and-even more-the third
      trimester of gestation. This lack of increase probably was due to placental
      compromise. Therefore, these steroid hormone variations may result in a lower
      humoral immune response activation, probably related to a change in the
      estrogen/androgen balance, that in turn could account for the decrease in disease
      activity observed during the third trimester in pregnant SLE patients.

PMID- 11954016
TI  - Retroperitoneal fibrosis: an extraarticular manifestation of ankylosing
      spondylitis.

PMID- 11954017
TI  - How to report radiographic data in randomized clinical trials in rheumatoid
      arthritis: guidelines from a roundtable discussion.

PMID- 11954019
TI  - Acquired C1 esterase inhibitor deficiency in two patients presenting with a lupus
      like syndrome and anticardiolipin antibodies.

PMID- 11954020
TI  - Evaluation of fine-needle aspiration cytology of breast masses in males.
AB  - BACKGROUND: The reliability of fine-needle aspiration cytology (FNAC) of breast
      masses in males could be compromised by lack of experience because breast
      carcinoma is rare in males and FNAC is not often used. In addition, FNAC of the
      more often encountered gynecomastia may lead to overdiagnosis. Therefore, in the
      current study the authors evaluated their experience with FNAC of breast masses
      occurring in males. METHODS: A total of 153 FNACs of the male breast obtained
      between 1985 until the end of 2000 were retrieved from the electronic files of
      the study institution. A total of 141 FNACs were taken from unilateral lesions in
      men age > 24 years, the group of men believed to be most at risk for breast
      carcinoma. Histologic follow-up was retrieved from the same files and was
      available for 72 FNACs. For specimens without histologic follow-up the nationwide
      pathology database was consulted and no cases of breast carcinoma were found.
      RESULTS: The inadequate rate was 13%. When inadequate FNACs were included in the
      calculations, the sensitivity was found to be 87% and the specificity 78%. When
      the inadequate FNACs were excluded from the calculations the sensitivity was
      reported to be 100% and the specificity 89%. The positive predictive value of a
      diagnosis of malignancy was 100%. During the study period the authors'
      institution examined approximately 10,000 FNAC specimens from male and female
      breasts and 399 resection specimens from the breasts of men age > 24 years with
      unilateral lesions. In this last group, preoperative FNAC reduced the benign-to
      malignant ratio from 19.8:1 to 3.5:1. CONCLUSIONS: FNAC of the male breast is a
      reliable procedure in a setting in which sufficient numbers of FNACs of the
      breast are examined. The authors believe FNAC should be used more often in the
      preoperative evaluation of breast lesions occurring in males.

PMID- 11954022
TI  - Classification of benign endometrial glandular cells in cervical smears from
      postmenopausal women.
AB  - BACKGROUND: The Bethesda System recommends reporting benign endometrial cells in
      cervical smears from postmenopausal (PMP) women as a glandular cell abnormality.
      However, PMP women on hormone replacement therapy (HRT) sometimes may experience
      endometrial shedding. The significance of such a finding has not been
      investigated in detail. METHODS: The authors evaluated 85 PMP women with cervical
      smears that contained benign endometrial glandular cells. Clinical information,
      including vaginal bleeding and the use of HRT or tamoxifen, was recorded, and
      follow-up was obtained. RESULTS: Thirty-three PMP women were not on HRT, and 11
      women were symptomatic. Twenty women underwent endometrial biopsy: Two
      symptomatic patients had endometrial adenocarcinoma, and 3 symptomatic patients
      and 1 asymptomatic patient had endometrial polyps. The frequency of abnormal
      findings was 18%. Forty-seven PMP women received HRT; 15 were symptomatic. Twenty
      two patients underwent endometrial biopsy: 1 symptomatic patient had cystic
      hyperplasia, and 2 symptomatic patients and 1 asymptomatic patient had an
      endometrial polyp. The frequency of abnormal findings was 8.5%. No one type of
      HRT was correlated with specific findings. Five PMP women were on tamoxifen, and
      two of them were symptomatic. Four patients underwent endometrial sampling: Two
      of them had an endometrial polyp, which was symptomatic in one patient.
      CONCLUSIONS: These data confirm that benign endometrial glandular cells in
      cervical smears from PMP women may indicate endometrial pathology, especially if
      vaginal bleeding is present. Although atypical endometrial hyperplasia or
      carcinoma was not identified in the group of PMP women on HRT, endometrial
      abnormalities of a lesser degree were present in 8.5% of patients. Thus, the
      authors favor continued classification of benign endometrial glandular cells in
      cervical smears of PMP women, whether or not they are on HRT, as a glandular cell
      abnormality.

PMID- 11954023
TI  - Interobserver variability: comparison between liquid-based and conventional
      preparations in gynecologic cytology.
AB  - BACKGROUND: Studies have shown that the ThinPrep Papanicolaou test (TP) increases
      the detection of epithelial cell abnormalities compared with the conventional
      preparation. Little is known about the interobserver variability of reporting
      gynecologic cytology results using the TP preparation and its comparison with
      results obtained using the conventional method. METHODS: To compare the
      interobserver variability between the TP method and the conventional method for
      reporting the diagnoses of gynecologic cytology, 20 pairs of conventional and TP
      slides (total, 40 slides) that were prepared from split samples were evaluated
      blindly by 19 cytotechnologists from three different laboratories. Each reviewer
      was asked to categorize each slide into the following five categories: within
      normal limits, benign cellular changes, atypical squamous cells of undetermined
      significance, low-grade squamous intraepithelial lesion (LSIL), and high-grade
      squamous intraepithelial lesion (HSIL). For both conventional and TP
      preparations, interobserver variability was analyzed using Spearman rank
      correlation coefficients. The mean correlation coefficients (weak, 0.0-0.4; fair,
      0.4-0.7; and strong, 0.7-1.0) between the TP method and the conventional method
      were then compared. RESULTS: The overall interobserver agreement as well as
      interobserver agreement within each laboratory was good for both TP and
      conventional preparations. Based on the set of conventional cervical smears, only
      one slide that was diagnosed as HSIL had unanimous agreement; whereas, based on
      the set of TP slides, three slides, including two diagnosed as HSIL and one
      diagnosed as LSIL, had a unanimous diagnosis. The difference in the interobserver
      agreement between TP and conventional methods, based on comparing their mean +/-
      standard deviation correlation coefficients (TP method, 0.84 +/- 0.081;
      conventional method, 0.82 +/- 0.105; P < 0.001), was statistically significant.
      CONCLUSIONS: Interobserver agreement in reporting gynecologic cytology using the
      TP method is good, particularly for squamous intraepithelial lesions, and appears
      to be superior to the conventional method.

PMID- 11954024
TI  - Hormonal effects of Depo-Provera in cervical smears: a comparison with Triphasil
      and postmenopausal effects.
AB  - BACKGROUND: Long-acting injectable contraceptive agents may cause changes in
      cervical smears that could impair the detection of epithelial abnormalities. The
      objectives of the current study were to 1) compare the hormonal effects of depot
      medroxyprogesterone acetate (Depo-Provera) (DP) in cervical smears with those of
      levonorgestrel and ethinyl estradiol (Triphasil) (TP) and postmenopausal (PM)
      changes; and 2) determine whether the duration of DP use affects squamous
      maturation. METHODS: Satisfactory cervical smears from 50 DP users, 55 TP users,
      and 51 PM patients were evaluated blindly for: 1) squamous cell curling,
      crowding, cytolysis, and navicular cell formation; 2) pseudoparakeratosis, blue
      blobs, and histiocytes; 3) endometrial cells and blood; 4) single or enlarged
      endocervical nuclei and mucin-depleted endocervical cells; 5) lactobacilli and
      coccobacilli amounts; and 6) squamous maturation (ratio of
      parabasal:intermediate:superficial cells). RESULTS: No statistically significant
      differences were observed for blue blobs, histiocytes, blood, endometrial cells,
      or single or enlarged endocervical nuclei among smears from the three groups.
      More smears from DP and TP users demonstrated squamous cell curling, crowding,
      and cytolysis as well as navicular cells and abundant lactobacilli compared with
      smears from PM patients. There were more PM smears with pseudoparakeratosis and
      mucin-depleted endocervical cells compared with the other groups. The majority of
      PM smears (98%) demonstrated predominantly parabasal cells with some intermediate
      cells. The majority of DP (86%) and TP (93%) smears demonstrated mostly
      intermediate and some superficial cells, regardless of the duration of DP use.
      CONCLUSIONS: Certain progestational-dependent effects (i.e., curling, crowding,
      navicular cells, and abundant lactobacilli) were identified more often in TP
      users compared with DP users and less often in PM patients. The mostly parabasal
      pattern observed in smears from PM patients contrasted with the predominantly
      intermediate pattern found in smears from DP and TP users. The duration of DP use
      did not appear to have any effect on squamous maturation.

PMID- 11954025
TI  - Concordance of histopathologic and cytologic grading in musculoskeletal sarcomas:
      can grades obtained from analysis of the fine-needle aspirates serve as the basis
      for therapeutic decisions?
AB  - BACKGROUND: Utilization of fine-needle aspiration (FNA) for the diagnosis of
      musculoskeletal lesions has been de-emphasized by many clinicians because of
      concerns regarding the technique's ability to supply all information necessary
      for prognostication and appropriate selection of therapy. Paramount among the
      concerns is the belief that FNA is incapable of supplying precise subtyping and
      grading in many cases. Secondary concerns regarding the use of FNA involve its
      perceived inability to supply adequate tissue for ancillary studies including
      immunohistochemistry and molecular diagnostic analysis. The authors investigated
      the ability of FNA to accurately subtype and grade a series of 107 primary
      sarcomas of the musculoskeletal system. METHODS: The files of the Departments of
      Pathology at Duke University Medical Center and the University of California at
      Los Angeles and the private consultation files of one of the authors were
      searched for all fine-needle aspirates of sarcomas arising within the
      musculoskeletal system. A total of 107 cases were obtained and reviewed by three
      board-certified cytopathologists. Each cytopathologist independently assigned
      subtype when possible and generated a grade for each of the sarcomas.
      Corresponding surgical material was available for 77 cases. The surgical material
      was re-reviewed for accuracy of diagnosis and assignment of grade independently
      of the cytologic examination. Correlation of cytologic grade with histopathologic
      grade was made and analyzed by the kappa test. In addition, agreement on grade
      between cytopathologists was analyzed, and accuracy of histologic subtype
      prediction by cytologic analysis was studied. RESULTS: Most of the sarcomas were
      cytologically graded as Grade 1 or 2 but were assigned a histologic grade of 2 or
      3. Cytopathologist A graded 93% of the sarcomas as either Grade 1 or 2,
      cytopathologist B graded 89% of cases as Grade 1 or 2, and cytopathologist C
      graded 94% of cases as Grade 1 or 2. Histologic evaluation demonstrated 82% of
      cases to be Grade 2 or 3. Correlation of cytologic and surgical grade varied
      among the observers. Cytopathologist A showed the highest degree of correlation
      between cytologic and surgical grade with an r value of 0.5. The corresponding r
      values for cytopathologists B and C were 0.46 and 0.41, respectively. Correlation
      between cytologic and surgical grade was significant for all three observers (P <
      0.001). Only nuclear grade showed a consistent correlation in predicting final
      surgical pathology grade. Cellularity, mitotic rate, and the presence of necrosis
      were not statistically significant for predicting histopathologic grade. Accurate
      exact subtyping by cytologic examination was achieved in approximately 55% of
      cases. Prediction of histopathologic subtype by cytologic analysis was most
      successful when a distinctive stroma was present or high-grade features
      indicative of malignant fibrous histiocytoma were observed. There was little
      agreement as to histopathologic type as predicated by cytology for low-grade
      spindle cell sarcomas. CONCLUSIONS: Although there was a statistically
      significant correlation between cytologically assigned grade and final
      histopathologic grade, statistical analysis revealed only a moderate correlation
      between the two with an overall r value of approximately 0.57. Cytologic analysis
      tended to undergrade in comparison to final histopathologic grading. Only
      analysis of nuclear atypia showed good correlation with final surgical grade.
      Fine-needle aspiration was only moderately successful at predicting
      histopathologic subtype for musculoskeletal sarcomas in this series.

PMID- 11954026
TI  - Can true papillary neoplasms of breast and their mimickers be accurately
      classified by cytology?
AB  - BACKGROUND: The cytologic accuracy in assessing malignancy in papillary breast
      neoplasms (PBNs) is controversial. This is further complicated by overlapping
      features observed in other breast lesions that produce papillary-like tissue
      fragments. METHODS: The authors reviewed 22 fine-needle aspirates (FNAs) from
      histologically proven papillary neoplasms: papillary carcinoma (PCA; 10
      aspirates) and intraductal papilloma (IDP; 12 aspirates). They also reviewed 8
      FNAs in which a papillary neoplasm was suggested by cytology but not confirmed by
      follow-up biopsy: fibroadenoma (6), mucinous carcinoma (1), and cribriform ductal
      carcinoma in situ (1). RESULTS: Papillary carcinoma can be distinguished from IDP
      by the higher cellularity, more complex papillae with thin disorganized fronds,
      mild to moderate nuclear atypia, and prominent dissociation with many single
      papillae. Fibrovascular cores (FVCs) were more common in PCA than IDP in which
      detached fibrous tissue fragments were frequently seen. Atypical IDP exhibited
      features intermediate between PCA and IDP. Apocrine metaplasia was variably
      present in IDP, atypical IDP, and fibroadenoma but absent in all carcinomas.
      Intraductal papilloma can be distinguished from fibroadenoma by their broad
      ruffled branches, scalloped borders, and tiny tongue-like projections. True
      papillae were commonly covered by tall columnar cells. Myoepithelial cells were
      few in IDP but were numerous in fibroadenoma. The epithelial fragments in
      nonpapillary lesions presented as cellular spheres and/or complex sheets with
      finger-like projections but lacked FVCs and columnar cells. CONCLUSIONS:
      Papillary breast neoplasms can be accurately classified by cytology. Closer
      evaluation of the tissue fragments architecture and the background can help in
      separating PBN from their mimics.

PMID- 11954027
TI  - The value of Wilms tumor susceptibility gene 1 in cytologic preparations as a
      marker for malignant mesothelioma.
AB  - BACKGROUND: It has been shown that detection of the Wilms tumor susceptibility
      gene 1 protein (WT1) has diagnostic utility in the distinction of mesothelioma
      from adenocarcinoma in tissue sections of pleural tumors. This
      immunohistochemical study evaluates the effectiveness of WT1 as a marker for
      malignant mesothelioma in paraffin sections of cell block preparations derived
      from effusion specimens. METHODS: The authors evaluated 111 cell blocks for WT1
      immunoreactivity, including 14 mesotheliomas and 97 metastatic adenocarcinomas
      from various sites. RESULTS: Nuclear reactivity for WT1 was observed in all
      samples of mesothelioma. However, only 22 of 97 samples (23%) of metastatic
      adenocarcinoma, nearly all of which were of ovarian origin (91%), exhibited
      nuclear reactivity for WT1. In 14 other samples (most of pulmonary derivation),
      WT1 staining restricted to the cytoplasm was observed for some tumor cells and
      was regarded as nonspecific. CONCLUSIONS: Based on this staining profile, WT1
      represents an effective marker for mesotheliomas in cell block preparations and
      can aid in its distinction from pulmonary adenocarcinoma. In assessment of
      effusion specimens with metastatic carcinoma, nuclear reactivity for WT1 is
      highly suggestive of an ovary primary tumor

PMID- 11954028
TI  - Adult T-cell leukemia/lymphoma: a cytopathologic, immunocytochemical, and flow
      cytometric study.
AB  - BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a postthymic
      lymphoproliferative neoplasm of T cells caused by human T-cell lymphotropic virus
      (HTLV-1). Most cases are found in Japan, the Caribbean basin, and West Africa.
      DESIGN: To identify diagnostic parameters for cytology in this neoplasm, the
      authors undertook a retrospective review of all ATLL samples from 1990 to 2000.
      RESULTS: One hundred fourteen samples from 34 patients with the diagnosis of ATLL
      were reviewed: 80 cerebrospinal fluids, 7 pleural effusions, 4 bronchoalveolar
      lavages, 2 peritoneal effusions as well as fine-needle aspirations of 15 lymph
      nodes, 4 subcutaneous lesions, and 2 breast nodules. Twenty-one patients were
      women and 13 were men, with an age range of 30 to 71 years. Morphologically, all
      specimens were characterized by the presence of a polymorphous population of
      lymphocytes ranging from small bland-appearing lymphocytes to large atypical ones
      with bizarre, multilobulated nuclei (flower-like or clover leaf cells) with
      coarse chromatin and prominent nucleoli. The cytoplasm was deeply basophilic with
      occasional vacuoles. Immunocytochemistry was performed on 17 specimens from 14
      patients. In all cases tested, tumor cells were immunoreactive for CD3, CD4, CD5,
      and CD25 and were nonimmunoreactive for CD7 and CD8. Flow cytometry was performed
      on 12 specimens from 9 patients. The tumor cells in all cases tested were
      positive for CD2, CD3, CD4, CD5, and CD25 and were negative for CD7. CONCLUSIONS:
      Despite the polymorphous nature of ATLL, diagnosis can be established by close
      attention to nuclear cytologic features in conjunction with ancillary studies
      such as immunocytochemistry and/or flow cytometry.

PMID- 11954029
TI  - DNA profiles and numeric histogram classifiers in nephrogenic adenoma.
AB  - BACKGROUND: The malignant potential of nephrogenic adenoma is still a matter of
      controversy and therapeutic regimens of this morphologic entity range from
      partial, even total cystectomy to watchful waiting. The objective of the current
      study was to evaluate several robust image cytometry-DNA histogram classifiers
      and to search among those for factors that separate a biologically nonaggressive
      metaplastic lesion from lesions with increased malignant potential. METHODS: The
      study included bladder irrigation specimens, 23 preceding transurethral resection
      of nephrogenic adenoma and 24 preceding resection of papillary bladder carcinoma.
      Feulgen-stained nuclei were imported to a static image analysis system, and
      densitometric data were interpreted by two different software programs.
      Histograms were described numerically by DNA index, 2c deviation index, and by
      5c/9c-exceeding and euploid polyploidy rates. In addition, an interpretation
      algorithm based on a dual parameter analysis with an integrated automatic
      threshold was used. RESULTS: The numeric classification of DNA histograms of
      patients suffering from nephrogenic adenoma resulted in DNA indices between 0.91
      and 1.15. The 2c deviation indices ranged from 0.03 to 0.43, and the 5c exceeding
      rates ranged from 0.0 to 1.58. None of the measurements showed nuclei exceeding
      9c. The p25-75 ranges of 2c deviation indices in nephrogenic adenoma and
      papillary urothelial carcinoma did not overlap. These findings might be explained
      by minor proliferative activity in nephrogenic adenoma. Euploid polyploidy rates
      less than 5% confirm this explanation. Risk analysis documented high risk only
      for those patients with nephrogenic adenomas who had proven transitional cell
      carcinoma in their history. CONCLUSIONS: DNA estimation by image cytometry of
      urinary bladder irrigation specimens appears able to separate papillary bladder
      lesions. The method detects those lesions with higher malignant potential but is
      limited in separating entities with low malignant potential. Comparison of the
      discriminative power of robust numeric DNA classifiers reveals the 2c deviation
      index superior to the widely used DNA index and the 5c exceeding rate in this
      material.

PMID- 11954030
TI  - Association between initial diagnostic procedure and hysteroscopy and abnormal
      peritoneal washing in patients with endometrial carcinoma.

PMID- 11954031
TI  - Organization of human hypothalamus in fetal development.
AB  - The organization of the human hypothalamus was studied in 33 brains aged from 9
      weeks of gestation (w.g.) to newborn, using immunohistochemistry for parvalbumin,
      calbindin, calretinin, neuropeptide Y, neurophysin, growth-associated protein
      (GAP)-43, synaptophysin, and the glycoconjugate 3-fucosyl- N-acetyl-lactosamine.
      Developmental stages are described in relation to obstetric trimesters. The first
      trimester (morphogenetic periods 9-10 w.g. and 11-14 w.g.) is characterized by
      differentiating structures of the lateral hypothalamic zone, which give rise to
      the lateral hypothalamus (LH) and posterior hypothalamus. The PeF differentiates
      at 18 w.g. from LH neurons, which remain anchored in the perifornical position,
      whereas most of the LH cells are displaced laterally. A transient supramamillary
      nucleus was apparent at 14 w.g. but not after 16 w.g. As the ventromedial nucleus
      differentiated at 13-16 w.g., three principal parts, the ventrolateral part, the
      dorsomedial part, and the shell, were revealed by distribution of calbindin,
      calretinin, and GAP43 immunoreactivity. The second trimester (morphogenetic
      periods 15-17 w.g., 18-23 w.g., and 24-33 w.g.) is characterized by
      differentiation of the hypothalamic core, in which calbindin- positive neurons
      revealed the medial preoptic nucleus at 16 w.g. abutted laterally by the
      intermediate nucleus. The dorsomedial nucleus was clearly defined at 10 w.g. and
      consisted of compact and diffuse parts, an organization that was lost after 15
      w.g. Differentiation of the medial mamillary body into lateral and medial was
      seen at 13-16 w.g. Late second trimester was marked by differentiation of
      periventricular zone structures, including suprachiasmatic, arcuate, and
      paraventricular nuclei. The subnuclear differentiation of these nuclei extends
      into the third trimester. The use of chemoarchitecture in the human fetus
      permitted the identification of interspecies nuclei homologies, which otherwise
      remain concealed in the cytoarchitecture.

PMID- 11954032
TI  - Two N-methyl-D-aspartate receptors in rat dorsal root ganglia with different
      subunit composition and localization.
AB  - N-methyl-D-aspartate (NMDA) receptors in sensory afferents participate in chronic
      pain by mediating peripheral and central sensitization. We studied the presence
      of NMDA receptor subunits in different types of primary afferents. Western blots
      indicated that rat dorsal root ganglia (DRG) contain NR1, NR2B, NR2C, and NR2D
      but not NR2A. Real-time RT-PCR showed that NR2B and NR2D were expressed at higher
      levels than NR2A and NR2C in DRG. Immunofluorescence with an antibody that
      recognized NR1 and another that recognized NR2A and NR2B showed that NR1 and NR2B
      colocalized in 90% of DRG neurons, including most A-fibers (identified by the
      presence of neurofilament 200 kDa). In contrast, an antibody recognizing NR2C and
      NR2D labeled only neurofilament-negative DRG profiles. This antibody stained
      practically all DRG cells that contained calcitonin gene-related peptide and
      neurokinins and those that bound isolectin B4. The percentage of cells
      immunoreactive for NR1, NR2A/NR2B, and NR2C/NR2D were the same in the T9, T12,
      L4, and L6 DRG. The intracellular distribution of the NR2 subunits was strikingly
      different: Whereas NR2A/NR2B immunoreactivity was found in the Golgi apparatus
      and occasionally at the plasma membrane, NR2C/NR2D immunoreactivity was found in
      the cytoplasm but not in the Golgi. The NR1 subunit was present throughout the
      cytoplasm and was more intense in the Golgi. These findings indicate that DRG
      neurons have two different NMDA receptors, one containing the NR1, NR2D, and
      possibly the NR2C subunits, found only in C-fibers, and the diheteromer NR1/NR2B,
      present in the Golgi apparatus of both A- and C-fibers.

PMID- 11954033
TI  - Postnatal development of nicotinamide adenine dinucleotide phosphate-diaphorase
      positive neurons in the retina of the golden hamster.
AB  - The histochemical method was used to investigate the postnatal development of
      nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) -positive
      neurons in retinas of the golden hamster. NADPH-d-positive neurons were
      discernible in the retina at postnatal day (P)1. From P4 onward to adulthood,
      when the retina acquired its laminated characteristics, NADPH-d- positive neurons
      were observed in the inner nuclear layer (INL) and the ganglion cell layer (GCL).
      Results showed that NADPH-d-positive neurons in INL and GCL followed different
      time courses and patterns in their development. NADPH-d-positive neurons in INL
      underwent a sharp increase from P4 to P8 (3.6-fold), followed by a decrease to
      46% of the maximum at P12. This value was maintained relatively constant to the
      adult level. The mean diameters of NADPH-d-positive neurons in INL, which were
      smaller than those in the GCL for all ages, increased from P8 to P12 and from P20
      to adulthood. As for neurons in the GCL, the increase in cell number was not so
      apparent for the earlier postnatal days until P20; thereafter, an obvious
      increase to the adult level was observed. The mean diameters of the NADPH-d
      positive cell bodies in the GCL increased with age, except for P16-P20, during
      which time there was a slight and insignificant decrease. The tendency of changes
      in cell density was basically similar to that of the total number for both the
      INL and the GCL. Between P12 and P20, the density distribution map of the NADPH-d
      positive neurons underwent dramatic changes: The highest density shifted from the
      upper central retina at the earlier postnatal days to the lower central retina in
      the adult. The two waves of increase in NADPH-d-positive neurons coincide with
      the process of axonal elongation and synaptogenesis and the acquisition of visual
      function and experience. It is suggested that these NADPH-d-positive neurons are
      related to these two developmental events.

PMID- 11954035
TI  - Ontogeny of gamma-aminobutyric acid-immunoreactive neuronal populations in the
      forebrain and midbrain of the sea lamprey.
AB  - Although brain organization in lampreys is of great interest for understanding
      evolution in vertebrates, knowledge of early development is very scarce. Here,
      the development of the forebrain and midbrain gamma-aminobutyric acid (GABA)
      ergic systems was studied in embryos, prolarvae, and small larvae of the sea
      lamprey using an anti-GABA antibody. Ancillary immunochemical markers, such as
      proliferating cell nuclear antigen (PCNA), calretinin, and serotonin, as well as
      general staining methods and semithin sections were used to characterize the
      territories containing GABA-immunoreactive (GABAir) neurons. Differentiation of
      GABAir neurons in the diencephalon begins in late embryos, whereas
      differentiation in the telencephalon and midbrain was delayed to posthatching
      stages. In lamprey prolarvae, the GABAir populations appear either as compact
      GABAir cell groups or as neurons interspersed among GABA-negative cells. In the
      telencephalon of prolarvae, a band of cerebrospinal fluid-contacting (CSF-c)
      GABAir neurons (septum) was separated from the major GABAir telencephalic band,
      the striatum (ganglionic eminence) primordium. The striatal primordium appears to
      give rise to most GABAir neurons observed in the olfactory bulb and striatum of
      early larval stages. GABAir populations in the dorsal telencephalon appear later,
      in 15-30-mm-long larvae. In the diencephalon, GABAir neurons appear in embryos,
      and the larval pattern of GABAir populations is recognizable in prolarvae. A
      small GABAir cluster consisting mainly of CSF-c neurons was observed in the
      caudal preoptic area, and a wide band of scattered CSF-c GABAir neurons extended
      from the preoptic region to the caudal infundibular recess. A mammillary GABAir
      population was also distinguished. Two compact GABAir clusters, one consisting of
      CSF-c neurons, were observed in the rostral (ventral) thalamus. In the caudal
      (dorsal) thalamus, a long band extended throughout the ventral tier. The nucleus
      of the medial longitudinal fascicle contained an early-appearing GABAir
      population. The paracommissural pretectum of prolarvae and larvae contained a
      large group of non-CSF-c GABAir neurons, although it was less compact than those
      of the thalamus, and a further group was found in the dorsal pretectum. In the
      midbrain of larvae, several groups of GABAir neurons were observed in the dorsal
      and ventral tegmentum and in the torus semicircularis. The development of
      GABAergic populations in the lamprey forebrain was similar to that observed in
      teleosts and in mouse, suggesting that GABA is a very useful marker for
      understanding evolution of forebrain regions. The possible relation between early
      GABAergic cell groups and the regions of the prosomeric map of the lamprey
      forebrain (Pombal and Puelles [ 1999] J. Comp. Neurol. 414:391-422) is discussed
      in view of these results and information obtained with ancillary markers.

PMID- 11954034
TI  - Projection patterns of commissural interneurons in the lumbar spinal cord of the
      neonatal rat.
AB  - We have studied the axonal projection patterns of commissural interneurons (CINs)
      in the neonatal rat spinal cord. Some CINs are integral components of the
      neuronal networks in the vertebrate spinal cord that generate locomotor activity.
      By using differential retrograde labeling protocols with fluorescent dextran
      amines, we show that CINs with ascending axons (ascending CINs, or aCINs) and
      CINs with descending axons (descending CINs, or dCINs) constitute largely
      different populations. We show that aCINs and dCINs occupy partially overlapping
      domains in the transverse plane. The aCINs are located at the dorsal margin,
      within the dorsal horn, centrally within the intermediate zone, and in the medial
      region of the ventral horn, whereas the dCINs are located predominantly among the
      ventral and central aCINs and in smaller numbers within the dorsal horn. The
      labeled aCINs and dCINs project for at least one and a half segment rostrally or
      caudally and are present in roughly equal numbers. We also demonstrate the
      presence of a third, smaller population of CINs whose axons bifurcate to project
      for at least one and a half segment both rostrally and caudally (adCINs). The
      adCINs are located predominantly among the central and ventral groups of aCINs
      and dCINs. Finally, we demonstrate the presence of CINs with axons projecting for
      fewer than one and a half segment in either direction. These "short-range CINs"
      are intermingled with the aCINs, dCINs, and adCINs. Our results provide an
      anatomical framework for further electrophysiological studies aimed at
      identifying the CINs that participate in the mammalian locomotor central pattern
      generator.

PMID- 11954037
TI  - Three truth-spots.

PMID- 11954036
TI  - Molecular characterization and cell-specific expression of a Manduca sexta
      FLRFamide gene.
AB  - FMRFamide-related peptides (FaRPs) are a large group of neuropeptides containing
      a common RFamide C-terminus; they have been identified in vertebrates and
      invertebrates. We have isolated the cDNA that encodes three FaRPs in the tobacco
      hornworm, Manduca sexta, including the amidated decapeptide F10. The larger FaRPs
      are the partially processed precursors of F10, a neuropeptide belonging to the
      myosuppressin family of peptides. The presence of all three FaRPs in different
      tissues suggests differential utilization of typical dibasic processing sites and
      atypical processing sites C-terminal to leucine residues. F10 mRNA was detected
      in the brain, nerve cord, and midgut, and the mRNA levels in the nervous system
      are dynamically regulated during development. In situ hybridization analysis
      localized the F10 mRNA to a variety of cell types within the central nervous
      system (CNS), a peripheral neurosecretory cell (L1), and midgut endocrine cells,
      which suggests diverse functions. Distribution of the F10-containing neurons
      within the central nervous system is segment-specific, and the developmental
      profile suggests that the F10 gene products may have stage-specific functions.
      Molecular characterization of the F10 gene has provided insights into its
      regulation and cell-specific distribution that will enhance our understanding of
      how these FaRPs modulate different physiological systems and ultimately behavior.

PMID- 11954038
TI  - Brave new worlds: trophallaxis and the origin of society in the early twentieth
      century.
AB  - Trophallaxis, the process of feeding by mutual regurgitation amongst insects, was
      named by the North American entomologist William Morton Wheeler in 1918. I argue
      that entomologists, both before and after 1918, saw mutual feeding as an integral
      part of the behavioral whole of the nest, and moreover related its explanatory
      power to theories about human society. In particular, feeding behavior was seen
      as the key to the riddle of the origin of sociality. I show how entomologists'
      precise interpretations of trophallaxis varied and explore the increasingly
      functional, sociological, and economic constructions of the phenomenon that they
      developed-without breaking with earlier tradition-into the early 1930s. The
      article ends by demonstrating how Aldous Huxley's bleak vision of humanity in the
      novel Brave New World, and its ambiguous prescription for meaningful life amidst
      the trappings of modernity, has much in common with metaphors generated by those
      studying ants.

PMID- 11954039
TI  - Utopianism in psychology: the case of Wilhelm Reich.
AB  - This article examines utopian elements in Wilhelm Reich's writings in his
      American phase (1939-1957) in order to illustrate utopian sources of dynamic
      psychology. Although there are scholars who have used the term "psychological
      utopia" and applied it to individual thinkers (Reich, Marcuse, Fromm) and to
      specific psychological disciplines (psychoanalysis, behaviorism, cognitive
      psychology), the term itself has remained elusive and vague. Furthermore, there
      have been few attempts to systematically examine utopian elements in twentieth
      century psychology in general and the basic assumptions of psychological
      utopianism in particular. While pointing out that Reich's orgonomic theories have
      no scientific merit, this article argues for the relevancy of his ideas for
      understanding the nature of utopianism in dynamic psychology.

PMID- 11954042
TI  - In vitro and in vivo characterization of [125I]iodomethyllycaconitine in the rat.
AB  - The in vitro and in vivo binding characteristics of [125I]iodomethyllycaconitine
      ([125I]iodoMLA) were determined in the rat. [125I]iodoMLA binding to rat cerebral
      cortex membranes was saturable and reversible and its specific binding
      represented approximately 70-80% of the total binding. [125I]iodoMLA labeled a
      single site with Kd = 1.8 +/- 0.4 nM and Bmax = 68 +/- 3 fmol/mg protein. Kinetic
      analysis revealed a t1/2 for association and dissociation of 10.5 +/- 3.1 and
      10.3 +/- 1.6 min, respectively. Pharmacological characterization of [125I]iodoMLA
      binding indicated that it was specific for the alpha7 nAChR. In vitro brain
      region binding studies revealed greater binding in regions known to contain high
      numbers of alpha7 nAChRs. The analysis of the biodistribution of intravenously
      administered [125I]iodoMLA indicated that it was rapidly cleared and exhibited
      poor brain penetration; nevertheless, the levels of [125I]iodoMLA in alpha7 nAChR
      rich target regions were significantly increased compared to the nontarget region
      (cerebellum) 60-120 min after administration. No metabolism of MLA by human liver
      S9 fraction was detected. Our results suggest that [125I]iodoMLA will be a useful
      radioligand to study the alpha7 nAChR in vitro and in vivo.

PMID- 11954044
TI  - The cholinergic system modulates kindling and kindling-induced mossy fiber
      sprouting.
AB  - In a previous study, our laboratory demonstrated that the intraventricular
      infusion of nerve growth factor (NGF) accelerated kindling rates and enhanced
      mossy fiber sprouting in the absence of noticeable kindling-associated neuronal
      loss. The purpose of the present study was to investigate whether these NGF
      effects were mediated via the cholinergic system. This study evaluated the
      effects of the cholinergic agonist pilocarpine and the cholinergic antagonist
      scopolamine on kindling rates and kindling-induced mossy fiber sprouting in adult
      rats. The results showed that pilocarpine accelerated kindling rates and enhanced
      kindling-induced mossy fiber sprouting in the CA3 region of the hippocampus,
      whereas scopolamine retarded kindling rates and blocked kindling-induced mossy
      fiber sprouting in the CA3 and IML regions. These findings suggest that the
      cholinergic system may contribute to the long-term structural and functional
      alterations that are characteristic of the kindled state. Moreover, these data
      provide support for the hypothesis that NGF infusions may mediate kindling and
      kindling-induced mossy fiber sprouting via regulation of the cholinergic system.

PMID- 11954043
TI  - Protection of dopaminergic nigrostriatal afferents by GDNF delivered by
      microspheres in a rodent model of Parkinson's disease.
AB  - The use of glial cell line-derived neurotrophic factor (GDNF) appears to be a
      promising strategy to promote survival and function of the nigrostriatal
      dopaminergic pathway damaged in Parkinson's disease (PD). However, effective
      intracerebral administration is required for optimal therapeutic benefit and
      tools to evaluate such therapies must be developed. A rodent model of PD was
      therefore developed using striatal injection of 6-hydroxydopamine (6-OHDA) with
      simultaneous implantation of GDNF-delivering microspheres. The effects of GDNF
      released from microspheres were assessed by classical methods such as amphetamine
      induced rotating behavior and tyrosine hydroxylase (TH) immunoreactivity, as well
      as by quantitative autoradiography using PE2I, a dopamine transporter (DAT)
      radiotracer, which is also suitable for SPET imaging in humans. 6-OHDA-lesioned
      animals that received microspheres without GDNF were used as controls. During the
      first 3 weeks after simultaneous lesion and implantation, the amphetamine-induced
      rotating behavior of GDNF-treated rats was improved compared to controls and an
      increase in TH expression (+26%) was measured in the striatum 6 weeks after
      lesion. In accordance with these results, an increase in striatal PE2I-labeled
      DAT density was obtained (+17%) after 3 and 6 weeks of treatment. In conclusion,
      this study demonstrates the neuroprotective action of GDNF delivered by
      microspheres and suggests that PE2I may be an appropriate radiotracer for use in
      SPET scintigraphy to follow up treatment of PD in humans.

PMID- 11954046
TI  - Activation of metabotropic glutamate receptors by repetitive stimulation in
      auditory cortex.
AB  - To determine whether metabotropic glutamate receptors (mGluRs) contribute to the
      responses of neurons to repetitive stimulation in the rat auditory cortex in
      vitro, five stimulus pulses were delivered at 2-100 Hz which elicited five
      depolarizing synaptic responses, f-EPSPs: f-EPSPs(1-5). Stimulus pulses 2-5
      delivered at low frequencies (2-10 Hz) elicited f-EPSPs(2-5) that were about 15%
      smaller than the response elicited by the first pulse (f-EPSP(1)). In the
      presence of the nonspecific mGluR agonist, ACPD, the amplitude of all f-EPSPs was
      40% smaller than predrug responses. APV, CNQX, or bicuculline (antagonists of
      NMDA-, AMPA/kainate-, and GABA(A)-receptors, respectively) did not change this
      effect of ACPD. The mGluR antagonist, MCPG, had no effect on f-EPSPs but did
      reduce the effect of ACPD. High-frequency stimulation (50-100 Hz) elicited f
      EPSPs that were smaller with each successive stimulus. In ACPD, f-EPSP(1) was 40%
      smaller than predrug, but f-EPSPs(3-5) were not changed compared to pre-ACPD f
      EPSPs(3-5), indicating that ACPD occludes the effect of repetitive stimulation.
      MCPG increased f-EPSP(5) by 15%, indicating that a portion of the reduction of f
      EPSPs during high-frequency stimulation is mediated by mGluRs. MCPG also
      partially blocked the effect of ACPD. In CNQX, ACPD only decreased EPSPs, but APV
      or bicuculline did not change the effect of ACPD. These results suggest that the
      successive reduction of f-EPSPs during a high-frequency train is partially a
      result of mGluR activation.

PMID- 11954045
TI  - Age differences in phosphodiesterase type-IV and its functional response to
      dopamine D1 receptor modulation in the living brain: a PET study in conscious
      monkeys.
AB  - The present study demonstrated the age-related changes in the striatal dopamine
      D1 receptor binding and its related cAMP second-messenger system in the living
      brains of conscious young (6.4 +/- 1.8 years old) and aged (19.5 +/- 3.3 years
      old) monkeys (Macaca mulatta) using positron emission tomography (PET). For
      quantitative analysis of D1 receptors, [11C]SCH23390 was used and
      phosphodiesterase type-IV (PDE-IV) activity, as an index of cAMP system, was
      estimated by two scans with R- and S-[11C]rolipram. Significant age-related
      decreases in D1 receptor binding were observed in the striatum and frontal
      cortex. Analysis of uptake of R- and S-[11C]rolipram indicated age-related
      decreases in PDE-IV activity showing 22.0 and 25.2% decreases in the striatum and
      frontal cortex, respectively, while no significant changes were observed in the
      cerebellum. With systemic preadministration of the dopamine D1 receptor
      antagonist SCH23390 (0.2, 0.6, and 2 mg/kg), the PDE-IV activities in the
      striatum and frontal cortex were dose-dependently suppressed in both age groups.
      However, the degree of suppression by SCH23390 was more marked in young than in
      aged monkeys. These results demonstrate that the striatal cAMP second-messenger
      system activity as well as its functional response to dopamine D1 antagonist
      showed age-related impairment in the brain.

PMID- 11954047
TI  - Acute methamphetamine administration upregulates NGFI-B mRNA expression in the
      striatum: co-localization with c-Fos immunoreactivity.
AB  - In this study, the effects of acute methamphetamine administration on expression
      of the nuclear transcription factor NGFI-B mRNA and its co-localization with c
      Fos immunoreactivity in the striatum were evaluated in animals receiving a single
      dose of methamphetamine (4 mg/kg) given at 2 or 6 h prior to perfusion. All
      animals received a daily saline injection for 6 days prior to methamphetamine
      treatment. We have found that, similar to c-fos activation, NGFI-B mRNA levels
      were significantly increased 2 h after methamphetamine treatment and returned to
      basal levels 6 h later. Induction of NGFI-B mRNA levels by methamphetamine was
      highest in central striatum as compared to the dorsomedial distribution pattern
      observed in control animals. After acute methamphetamine treatment, the
      distribution pattern of NGFI-B mRNA upregulation was very similar to that of
      methamphetamine induced c-Fos immunoreactivity. However, co-localization studies
      with c-Fos immunoreactivity showed that not all NGFI-B-positive cells contained c
      Fos after methamphetamine treatment. Forty-five percent of all NGFI-B mRNA
      expressing neurons contained c-Fos immunoreactivity in the dorsomedial striatum
      as compared to 60% in central and 35% in ventrolateral striatum. This study
      provides a detailed description of the differential spatial and temporal
      modulation of NGFI-B and c-Fos expression in the striatum by acute
      methamphetamine treatment over time.

PMID- 11954048
TI  - Differential regulation of GAD67, enkephalin and dynorphin mRNAs by chronic
      intermittent L-dopa and A2A receptor blockade plus L-dopa in dopamine-denervated
      rats.
AB  - Adenosine A2A receptor antagonists have been proposed as an effective therapy in
      the treatment of Parkinson's disease. In the present study, we compared the
      modifications on striatal glutamate decarboxylase (GAD67), enkephalin, and
      dynorphin mRNA levels produced by a chronic-intermittent administration of L-3,4
      dihydroxyphenyl-alanine (L-dopa) (6 mg/kg) with those produced by the adenosine
      A2A receptor antagonist SCH 58261 (5 mg/kg) plus L-dopa (3 mg/kg) in unilaterally
      6-hydroxydopamine (6-OHDA)-lesioned rats. As previously reported, L-dopa (6
      mg/kg) and SCH 58261 (5 mg/kg) plus L-dopa (3 mg/kg) produced the same degree of
      turning behavior after the first administration. However, while L-dopa (6 mg/kg)
      induced a sensitized turning behavior response during the course of the
      treatment, which indicated a dyskinetic potential, SCH 58261 (5 mg/kg) plus L
      dopa (3 mg/kg) produced a stable turning behavior response, which was predictive
      of absence of dyskinetic side effects. Unilateral 6-OHDA lesion produced an
      elevation in striatal GAD67 and enkephalin mRNA levels and to a decrease in
      dynorphin mRNA levels. Chronic-intermittent L-dopa (6 mg/kg) treatment increased
      the striatal levels of GAD67, dynorphin, and enkephalin mRNA in the lesioned side
      as compared to the vehicle treatment. Chronic-intermittent SCH 58261 (5 mg/kg)
      plus L-dopa (3 mg/kg) as well as L-dopa (3 mg/kg) or SCH 58261 (5 mg/kg) alone
      did not produce any significant modification in GAD67, dynorphin, or enkephalin
      mRNA levels in the lesioned striatum as compared to the striatum of vehicle
      treated rats. The results show that combined SCH 58261 plus L-dopa did not
      produce long-term changes in markers of striatal efferent neurons activity and
      suggest that the lack of modifications in GAD67 and dynorphin mRNA after SCH
      58261 plus L-dopa might correlate with the lack of turning behavior sensitization
      which predicts drug dyskinetic potential.

PMID- 11954049
TI  - "Nonhedonic" food motivation in humans involves dopamine in the dorsal striatum
      and methylphenidate amplifies this effect.
AB  - The drive for food is one of the most powerful of human and animal behaviors.
      Dopamine, a neurotransmitter involved with motivation and reward, its believed to
      regulate food intake in laboratory animals by modulating its rewarding effects
      through the nucleus accumbens (NA). Here we assess the involvement of dopamine in
      "nonhedonic" food motivation in humans. Changes in extracellular dopamine in
      striatum in response to nonhedonic food stimulation (display of food without
      consumption) were evaluated in 10 food-deprived subjects (16-20 h) using positron
      emission tomography (PET) and [11C]raclopride (a D2 receptor radioligand that
      competes with endogenous dopamine for binding to the receptor). To amplify the
      dopamine changes we pretreated subjects with methylphenidate (20 mg p.o.), a drug
      that blocks dopamine transporters (mechanism for removal of extracellular
      dopamine). Although the food stimulation when preceded by placebo did not
      increase dopamine or the desire for food, the food stimulation when preceded by
      methylphenidate (20 mg p.o.) did. The increases in extracellular dopamine were
      significant in dorsal (P < 0.005) but not in ventral striatum (area that included
      NA) and were significantly correlated with the increases in self-reports of
      hunger and desire for food (P < 0.01). These results provide the first evidence
      that dopamine in the dorsal striatum is involved in food motivation in humans
      that is distinct from its role in regulating reward through the NA. In addition
      it demonstrates the ability of methylphenidate to amplify weak dopamine signals.

PMID- 11954050
TI  - Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of
      rats behaviorally sensitized to methamphetamine.
AB  - We investigated changes in signal transduction via calcineurin (CaN) in the
      striatum of rats behaviorally sensitized to methamphetamine (Meth). The rats were
      injected with Meth (4 mg/kg, s.c.) five times a week for 3 weeks and then were
      given a challenge dose of Meth (2 mg/kg, s.c.). Seven days after the challenge
      test, we determined the levels of CaN Aalpha and Abeta by Western blotting. We
      further immunoquantified DARPP-32 (dopamine- and cAMP-regulated phosphoprotein,
      mw 32,000) and phosphothreonine-DARPP-32, which can be dephosphorylated at
      threonine sites by CaN. We found that both CaN Aalpha and Abeta were
      significantly decreased in the particulate fractions but were not changed in the
      soluble fractions from the striatum of Meth-sensitized rats as compared with
      control rats. The same findings were observed in the striatum of rats 6 h after
      the injection of PCP (10 mg/kg, s.c.). In the striatum of Meth-sensitized rats,
      phosphothreonine-DARPP-32 immunoreactivities significantly increased, but DARPP
      32 immunoreactivities were not significantly different from those of the control
      rats. These results indicate that the activity of signal transduction via CaN is
      functionally decreased in the striatum of Meth-sensitized rats.

PMID- 11954051
TI  - Release and uptake of catecholamines in the bed nucleus of the stria terminalis
      measured in the mouse brain slice.
AB  - The release and clearance of electrically evoked catecholamine (CA) in the
      ventral portion of the bed nucleus of the stria terminalis (BSTV) in mouse brain
      slices was evaluated with fast-scan cyclic voltammetry at carbon-fiber
      microelectrodes (CFME). Uptake in this region was observed to be markedly slower
      than in the caudate putamen (CPu). Clearance rates were reduced in the BSTV in
      both norepinephrine transporter knockout (NET KO) and dopamine transporter
      knockout (DAT KO) mice when compared to results in wild-type (WT) mice. However,
      uptake was faster in the BSTV in both the DAT and NET KO mice than in the CPu of
      DAT KO mice. This indicates that both transporters play a role in CA clearance in
      the BSTV. The transporters restrict extracellular CA to the general area of the
      BSTV, as revealed by the diminished signal as the CFME is moved sequentially
      further and further from the site where CA release is evoked. However, in slices
      from the DAT KOs and NET KOs, CA release could be observed outside of the BSTV
      region during such experiments. These results show that the low rate uptake in
      the BSTV facilitates extrasynaptic diffusion of catecholamine, but that uptake
      still regulates and limits the range of the transmitter to the region. Slower
      clearance from the extracellular fluid allows the released CA to act as a volume
      transmitter and diffuse to distant sites within the region to exert its
      neurochemical action.

PMID- 11954052
TI  - Density and affinity of the dopamine D2 receptors in aged symptomatic and
      asymptomatic MPTP-treated monkeys: PET studies with [11C]raclopride.

PMID- 11954053
TI  - Thermodynamic analysis of the interaction between proteins and solid surfaces:
      application to liquid chromatography.

PMID- 11954054
TI  - Functional mapping of conserved, surface-exposed charges of antibody variable
      domains.
AB  - Surface-exposed charges can affect protein structure, stability and solubility as
      well as the kinetics of both the folding process and interaction with binding
      partners. We have investigated the influence on kinetic interaction parameters of
      14 conserved, surface-exposed charges located away from the paratope in the
      variable domains of two antibodies of different specificity. We found that
      conserved, surface-exposed, charged framework residues are asymmetrically
      distributed on opposite faces of both VH and VL domains. Some of the charges play
      a critical role in protein folding and stability. While electrostatic forces
      within or close to the binding interface can be used to optimize the association
      rate, we confirmed the predicted minor effects of charge modifications remote
      from the binding site. They had no effect on the dissociation rate parameter. Our
      study demonstrates the role of residues remote from the interaction site in the
      recognition function as well as the limited effect of surface charge
      modifications in antibody fragments on kinetic interaction parameters.

PMID- 11954056
TI  - Changes in cerebellar activation pattern during two successive sequences of
      saccades.
AB  - The changes in the cerebellar activation pattern of two successive fMRI scanning
      runs were determined for visually guided to-and-fro saccades in 12 healthy
      volunteers familiar with the study paradigm. Group and single subject-analyses
      revealed a constant activation of the paramedian cerebellar vermis (uvula,
      tonsils, tuber, folium/declive), which reflects constant ocular motor activity in
      both runs. A significant decrease in activation of the cerebellar hemispheres
      found in the second run is best explained by either a decrease in attention or
      the effects of motor optimization and learning. The significant, systematic
      changes of the cerebellar activation pattern in two successive runs were not
      expected, because the ocular motor task was simple, familiar, and highly
      automated. These findings indicate that similar effects may bias other cerebellar
      activation studies, in which sensorimotor tasks are repeated in a single session.

PMID- 11954055
TI  - A computational analysis of substrate binding strength by phosphorylase kinase
      and protein kinase A.
AB  - Protein kinases exhibit various degrees of substrate specificity. The large
      number of different protein kinases in the eukaryotic proteomes makes it
      impractical to determine the specificity of each enzyme experimentally. To test
      if it were possible to discriminate potential substrates from non-substrates by
      simple computational techniques, we analysed the binding enthalpies of modelled
      enzyme-substrate complexes and attempted to correlate it with experimental enzyme
      kinetics measurements. The crystal structures of phosphorylase kinase and cAMP
      dependent protein kinase were used to generate models of the enzyme with a series
      of known peptide substrates and non-substrates, and the approximate enthalpy of
      binding assessed following energy minimization. We show that the computed
      enthalpies do not correlate closely with kinetic measurements, but the method can
      distinguish good substrates from weak substrates and non-substrates.

PMID- 11954057
TI  - Characterizing instantaneous phase relationships in whole-brain fMRI activation
      data.
AB  - Typically, fMRI data is processed in the time domain with linear methods such as
      regression and correlation analysis. We propose that the theory of phase
      synchronization may be used to more completely understand the dynamics of
      interacting systems, and can be applied to fMRI data as a novel method of
      detecting activation. Generalized synchronization is a phenomenon that occurs
      when there is a nonlinear functional relationship present between two or more
      coupled, oscillatory systems, whereas phase synchronization is defined as the
      locking of the phases while the amplitudes may vary. In this study, we developed
      an application of phase synchronization analysis that is appropriate for fMRI
      data, in which the phase locking condition is investigated between a voxel time
      series and the reference function of the task performed. A synchronization index
      is calculated to quantify the level of phase locking, and a nonparametric
      permutation test is used to determine the statistical significance of the
      results. We performed the phase synchronization analysis on the data from five
      volunteers for an event-related finger-tapping task. Functional maps were created
      that provide information on the interrelations between the instantaneous phases
      of the reference function and the voxel time series in a whole-brain fMRI
      activation data set. We conclude that this method of analysis is useful for
      revealing additional information on the complex nature of the fMRI time series.

PMID- 11954058
TI  - Motor cortex involvement during verbal versus non-verbal lip and tongue
      movements.
AB  - We evaluated left and right motor cortex involvement during verbal and non-verbal
      lip and tongue movements in seven healthy subjects using whole-head
      magnetoencephalography. The movements were paced by tone pips. The non-verbal
      tasks included a kissing movement and touching the teeth with the tongue. The
      verbal tasks comprised silent articulation of the Finnish vowel /o/, which
      requires mouth movement similar to that in the kissing task, pronouncing the same
      self-selected word repeatedly, and producing a new word for every tone pip. Motor
      cortex involvement was quantified by task-related suppression and subsequent
      rebound of the 20-Hz activity. The modulation concentrated to two sites along the
      central sulcus, identified as the motor face and hand representations. The 20-Hz
      suppression in the face area was relatively similar during all tasks. The post
      movement rebound, however, was significantly left-lateralized during word
      production. In the non-verbal tasks, hand areas showed pronounced suppression of
      20-Hz activity that was significantly diminished for the verbal tasks. The
      latencies of the 20-Hz suppression in the left and right face representations
      were correlated across subjects during verbal mouth movements. Increasing
      linguistic content of lip and tongue movements was thus manifested in spatially
      more focal motor cortex involvement, left-hemisphere lateralization of face area
      activation, and correlated timing across hemispheres.

PMID- 11954060
TI  - Visual detection of motion speed in humans: spatiotemporal analysis by fMRI and
      MEG.
AB  - Humans take a long time to respond to the slow visual motion of an object. It is
      not known what neural mechanism causes this delay. We measured
      magnetoencephalographic neural responses to light spot motion onset within a wide
      speed range (0.4-500 degrees /sec) and compared these with human reaction times
      (RTs). The mean response latency was inversely related to the speed of motion up
      to 100 degrees /sec, whereas the amplitude increased with the speed. The response
      property at the speed of 500 degrees /sec was different from that at the other
      speeds. The speed-related latency change was observed when the motion duration
      was 10 msec or longer in the speed range between 5 and 500 degrees /sec,
      indicating that the response is directly related to the speed itself. The source
      of the response was estimated to be around the human MT+ and was validated by
      functional magnetic imaging study using the same stimuli. The results indicate
      that the speed of motion is encoded in the neural activity of MT+ and that it can
      be detected within 10 msec of motion observation. RT to the same motion onset was
      also inversely related to the speed of motion but the delay could not be
      explained by the magnetic response latency change. Instead, the reciprocal of RT
      was linearly related to the reciprocal of the magnetic response latency,
      suggesting that the visual process interacts with other neural processes for
      decision and motor preparation.

PMID- 11954059
TI  - Sensory system interactions during simultaneous vestibular and visual stimulation
      in PET.
AB  - The patterns of regional cerebral blood flow (rCBF) increases and decreases in
      PET were compared for unimodal vestibular, unimodal visual, and for simultaneous
      vestibular and visual stimulation. Thirteen healthy volunteers were exposed to a)
      caloric vestibular stimulation, b) small-field visual motion stimulation in roll,
      c) simultaneous caloric vestibular and visual pattern stimulation. Unimodal
      vestibular stimulation led to activations of vestibular cortex areas, in
      particular the parieto-insular vestibular cortex (PIVC), and concurrent
      deactivations of visual cortical areas [Brodmann area (BA) 17-19]. Unimodal
      visual motion stimulation led to activations of the striate visual cortex and the
      motion-sensitive area in the middle temporal/middle occipital gyri (BA 19/37)
      with concurrent deactivations in the PIVC. Simultaneous bimodal stimulation
      resulted in activations of the cortical representation of both sensory
      modalities. In the latter condition activations and deactivations were
      significantly smaller compared to unimodal stimulation. The findings are
      consistent with the concept of an inhibitory reciprocal vestibulo-visual
      interaction in all three stimulus conditions.

PMID- 11954061
TI  - Prefrontal cortex involvement in processing incorrect arithmetic equations:
      evidence from event-related fMRI.
AB  - The main aim of this study was to investigate the differential processing of
      correct and incorrect equations to gain further insight into the neural processes
      involved in arithmetic reasoning. Electrophysiological studies in humans have
      demonstrated that processing incorrect arithmetic equations (e.g., 2 + 2 = 5)
      elicits a prominent event-related potential (ERP) compared to processing correct
      equations (e.g., 2 + 2 = 4). In the present study, we investigated the neural
      substrates of this process using event-related functional magnetic resonance
      imaging (fMRI). Subjects were presented with arithmetic equations and asked to
      indicate whether the solution displayed was correct or incorrect. We found
      greater activation to incorrect, compared to correct equations, in the left
      dorsolateral prefrontal cortex (DLPFC, BA 46) and the left ventrolateral
      prefrontal cortex (VLPFC, BA 47). Our results provide the first brain imaging
      evidence for differential processing of incorrect vs. correct equations. The
      prefrontal cortex activation observed in processing incorrect equations overlaps
      with brain areas known to be involved in working memory and interference
      processing. The DLPFC region differentially activated by incorrect equations was
      also involved in overall arithmetic processing, whereas the VLPFC was activated
      only during the differential processing of incorrect equations. Differential
      response to correct and incorrect arithmetic equations was not observed in
      parietal cortex regions such as the angular gyrus and intra-parietal sulcus,
      which are known to play a specific role in performing arithmetic computations.
      The pattern of brain response observed is consistent with the hypothesis that
      processing incorrect equations involves detection of an incorrect answer and
      resolution of the interference between the internally computed and externally
      presented incorrect answer. More specifically, greater activation during
      processing of incorrect equations appears to reflect additional operations
      involved in maintaining the results in working memory, while subjects attempt to
      resolve the conflict and select a response. These findings allow us to further
      delineate and dissociate the contributions of prefrontal and parietal cortices to
      arithmetic reasoning.

PMID- 11954064
TI  - The first clinical application of a "hands-on" robotic knee surgery system.
AB  - The performance of a novel "hands-on" robotic system for total knee replacement
      (TKR) surgery is evaluated. An integrated robotic system for accurately machining
      the bone surfaces in TKR surgery is described. Details of the system, comprising
      an "active constraint" robot, called Acrobot, a "gross positioning" robot, and
      patient clamps, are provided. The intraoperative protocol and the preoperative,
      CT-based, planning system are also described. A number of anatomical registration
      and cutting trials, using plastic bones, are described, followed by results from
      two preliminary clinical trials, which demonstrate the accuracy achieved in the
      anatomical registration. Finally, the first clinical trial is described, in which
      the results of the anatomical registration and bone cutting are seen to be of
      high quality. The Acrobot system has been successfully used to accurately
      register and cut the knee bones in TKR surgery. This demonstrates the great
      potential of a "hands-on" robot for improving accuracy and increasing safety in
      surgery.

PMID- 11954063
TI  - State of the art in surgical robotics: clinical applications and technology
      challenges.
AB  - Although it has been over 15 years since the first recorded use of a robot for a
      surgical procedure, the field of medical robotics is still an emerging one that
      has not yet reached a critical mass. Although robots have the potential to
      improve the precision and capabilities of physicians, the number of robots in
      clinical use is still very small. In this review article, we begin with a short
      historical review of medical robotics, followed by an overview of clinical
      applications where robots have been applied. The clinical applications are then
      discussed; they include neurosurgery, orthopedics, urology, maxillofacial
      surgery, radiosurgery, ophthalmology, and cardiac surgery. We conclude with a
      listing of technology challenges and research areas, including system
      architecture, software design, mechanical design, imaging compatible systems,
      user interface, and safety issues.

PMID- 11954065
TI  - A six-degree-of-freedom passive arm with dynamic constraints (PADyC) for cardiac
      surgery application: preliminary experiments.
AB  - The purpose of Computer-Assisted Surgery (CAS) is to help physicians and surgeons
      plan and execute optimal strategies from multimodal image data. The execution of
      such planned strategies may be assisted by guidance systems. Some of these
      systems, called synergistic systems, are based on the cooperation of a robotic
      device with a human operator. We have developed such a synergistic device: PADyC
      (Passive Arm with Dynamic Constraints). The basic principle of PADyC is to have a
      manually actuated arm that dynamically constrains the authorized motions of the
      surgical tool held by the human operator during a planned task. Dynamic
      constraints are computed from the task definition, and are implemented by a
      patented mechanical system. In this paper, we first introduce synergistic systems
      and then focus on modeling and algorithmic issues related to the dynamic
      constraints. Finally, we describe a 6-degree-of-freedom prototype robot designed
      for a clinical application (cardiac surgery) and report on preliminary
      experiments to date. The experimental results are then discussed, and future work
      is proposed.

PMID- 11954066
TI  - CT-integrated robot for interventional procedures: preliminary experiment and
      computer-human interfaces.
AB  - Pre-operative planning and intra-operative computer interfaces for minimally
      invasive interventions were investigated with an active robot integrated with a
      CT scanner. To test the robotic system, a biopsy study was performed using a pig.
      For pre-operative planning, a virtual needle was superimposed on axial slices and
      multiplanar reformatted views in correlation with the interventional field. The
      path of the virtual needle was sent to the robot's controller, and the robot's
      needle gripper moved into a position congruent with the planned path. Intra
      operative controls were then used to drive the needle while keeping the
      interventionalist's hands out of the direct X-ray beam during CT fluoroscopy.
      After needle insertion, the imaged and virtual needles were shown to be
      sufficiently congruent.

PMID- 11954067
TI  - URobotics--Urology Robotics at Johns Hopkins.
AB  - URobotics (Urology Robotics) is a program of the Urology Department at the Johns
      Hopkins Medical Institutions dedicated to the development of new technology for
      urologic surgery (http://urology.jhu.edu/ urobotics). The program is unique in
      that it is the only academic engineering program exclusively applied to urology.
      The program combines efforts and expertise from the medical and engineering
      fields through a close partnership of clinical and technical personnel. Since its
      creation in 1996, the URobotics lab has created several devices, instruments, and
      robotic systems, several of which have been successfully used in the operating
      room. This article reviews the technology developed in our laboratory and its
      surgical applications, and highlights our future directions.

PMID- 11954068
TI  - System for robotically assisted percutaneous procedures with computed tomography
      guidance.
AB  - We present the prototype of an image-guided robotic system for accurate and
      consistent placement of percutaneous needles in soft-tissue targets under CT
      guidance inside the gantry of a CT scanner. The couch-mounted system consists of
      a seven-degrees-of-freedom passive mounting arm, a remote center-of-motion robot,
      and a motorized needle-insertion device. Single-image-based coregistration of the
      robot and image space is achieved by stereotactic localization using a miniature
      version of the BRW head frame built into the radiolucent needle driver. The
      surgeon plans and controls the intervention in the scanner room on a desktop
      computer that receives DICOM images from the scanner. The system does not need
      calibration, employs pure image-based registration, and does not utilize any
      vendor-specific hardware or software features. In the open air, where there is no
      needle-tissue interaction, we systematically achieved an accuracy better than 1
      mm in hitting targets at 5-8 cm from the fulcrum point. In the phantom, the
      orientation accuracy was 0.6 degrees, and the distance between the needle tip and
      the target was 1.04 mm. Experiments indicated that this robotic system is
      suitable for a variety of percutaneous clinical applications.

PMID- 11954069
TI  - It's a perfect combination. The Philippines, a country that trains more nurses
      than it actually needs, supplying the UK, an island with a severe nursing
      shortage.

PMID- 11954070
TI  - Together we're stronger.

PMID- 11954071
TI  - Fleeced in the Philippines.

PMID- 11954072
TI  - Hands across the water.

PMID- 11954073
TI  - 9 hints on how to get to grips with the UK.

PMID- 11954074
TI  - Different from the average student.

PMID- 11954075
TI  - Bedford nurses are dedicated and skilled under pressure.

PMID- 11954077
TI  - Nurse not at fault in needlestick injury case.

PMID- 11954076
TI  - Stop these deadly diseases.

PMID- 11954078
TI  - A warmer reception in frozen foods than the NHS.

PMID- 11954079
TI  - Bully for you ... or is it?

PMID- 11954080
TI  - Should we be recruiting volunteers to work in hospitals?

PMID- 11954081
TI  - Relative values. 'More demanding than the patients'.

PMID- 11954082
TI  - Keeping nurses nursing: a quantitative analysis.

PMID- 11954083
TI  - Support for student training: a new role as demonstrators.

PMID- 11954084
TI  - Making sense of probiotics.

PMID- 11954085
TI  - Managing type 2 diabetes: a dynamic approach.

PMID- 11954086
TI  - Hypothermia--1. Assessment.

PMID- 11954087
TI  - Fit for practice. Part 2.3: The code in practice.

PMID- 11954088
TI  - Careers Focus. Specialist pathways.

PMID- 11954090
TI  - Retention. Nurses stay while teachers walk.

PMID- 11954091
TI  - RCN election manifesto. Nurses urged to get political.

PMID- 11954089
TI  - Working conditions. Nurses to take action over stress.

PMID- 11954092
TI  - Mental health. Risk from mentally ill is exaggerated.

PMID- 11954093
TI  - Decontamination of nebulisers.

PMID- 11954094
TI  - Theory to practice. Aseptic non-touch technique.

PMID- 11954095
TI  - Opportunity knocks in anaesthetics.

PMID- 11954097
TI  - Heads in the sand on racism.

PMID- 11954096
TI  - Screening. Get men's bellies on telly.

PMID- 11954098
TI  - Good porridge is satisfying, but mind the lumps.

PMID- 11954099
TI  - Community treatment orders will make mental health nurses' jobs easier.

PMID- 11954100
TI  - Sharp practice.

PMID- 11954101
TI  - Advocacy: a role too far for nurses.

PMID- 11954102
TI  - Mental health. Dollar values.

PMID- 11954103
TI  - Using action research: an introduction.

PMID- 11954104
TI  - Acromegaly management in the community.

PMID- 11954105
TI  - Listening to the experts.

PMID- 11954106
TI  - Inspiring confidence in new nurses.

PMID- 11954107
TI  - Managing malignant fungating lesions.

PMID- 11954108
TI  - Systems and diseases. Exploring normal anatomy and physiology. Nervous system. 5.

PMID- 11954109
TI  - Infection control. CJD fears prompt cash for tonsil ops.

PMID- 11954110
TI  - Meningitis C. Huge workload led to neglect of basic care.

PMID- 11954112
TI  - Psychosexual therapy. Television spotlight on sexual healing.

PMID- 11954111
TI  - Infection control. Private cleaners lose their sparkle.

PMID- 11954113
TI  - Environment. Socket to them.

PMID- 11954115
TI  - Nursing history. Waging war on the causes of ill health.

PMID- 11954114
TI  - Information technology. E-normous effort to reap net gains.

PMID- 11954116
TI  - Do government health promotion campaigns really work?

PMID- 11954117
TI  - Low risk = good practice + safer needles.

PMID- 11954118
TI  - Give ODAs a chance.

PMID- 11954119
TI  - Time to scale down nursing research.

PMID- 11954120
TI  - A little bit of knowledge....

PMID- 11954121
TI  - Learn from your mistakes.

PMID- 11954122
TI  - Military nursing. Action stations.

PMID- 11954124
TI  - Nurses need a clear line from their employers on covert medication.

PMID- 11954125
TI  - Blood pressure measurement.

PMID- 11954123
TI  - Clean, modern, inhuman.

PMID- 11954126
TI  - Care of patients on the move.

PMID- 11954127
TI  - Improving rehabilitation care.

PMID- 11954128
TI  - Dialectical behavioural therapy: a working perspective.

PMID- 11954129
TI  - Covert Administration. Row over UKCC's advice on drugs.

PMID- 11954131
TI  - Fit for practice.

PMID- 11954130
TI  - Government campaign. Bid to convince public MMR is safe.

PMID- 11954132
TI  - Trial removal of a catheter.

PMID- 11954133
TI  - Internet adoption. Confusion over twins' health care.

PMID- 11954134
TI  - Acute mental health nursing.

PMID- 11954135
TI  - Health and safety. Watchdogs wake up to NHS stress.

PMID- 11954136
TI  - National Institute for Clinical Excellence. Alzheimer's drugs given go-ahead.

PMID- 11954138
TI  - Nurse prescribing. Doctors divided on nurses' role.

PMID- 11954137
TI  - Psychiatric care. 'Patients don't know who does what, or why'.

PMID- 11954139
TI  - Breast augmentation. More than a storm in a D cup.

PMID- 11954140
TI  - Emergency contraception. Perils of popping into boots for a Levonelle.

PMID- 11954141
TI  - Licensed to kill superbugs. Will a new class of antibiotic cut the incidence of
      hospital-acquired infections?

PMID- 11954142
TI  - Should school nurses be dispensing emergency contraception?

PMID- 11954143
TI  - A painful experience.

PMID- 11954144
TI  - The case for sleeping on the job.

PMID- 11954145
TI  - The devil you know.

PMID- 11954146
TI  - You can't manage without us. Managers and nurses need to join forces to raise
      standards of care.

PMID- 11954147
TI  - No more Mr Bad Guy, please. Prejudices often get in the way of managers and
      nurses working effectively as a team.

PMID- 11954148
TI  - Trading places.

PMID- 11954149
TI  - Meeting the needs of older people in rehabilitation care.

PMID- 11954150
TI  - Evidence-based psychological interventions in mental health nursing.

PMID- 11954151
TI  - A framework for nursing the dying patient in ICU.

PMID- 11954152
TI  - Postural hypotension: symptoms and management.

PMID- 11954153
TI  - Recruitment. HIV tests for overseas staff.

PMID- 11954154
TI  - Measuring lying and standing BP--2.

PMID- 11954155
TI  - Infection control guidelines. Hand-washing cuts HAI rate.

PMID- 11954156
TI  - Needlestick injury. Anti-HIV drug branded 'lethal'.

PMID- 11954157
TI  - Nurse prescribing. Unions push DoH on controlled drugs.

PMID- 11954158
TI  - Anna Climbie. Trusts failed to spot hideous abuse.

PMID- 11954160
TI  - Crackdown on organ consent.

PMID- 11954159
TI  - Depleted uranium contamination. Testing for Gulf nurses.

PMID- 11954161
TI  - Conflict over organs' value to research.

PMID- 11954162
TI  - Recognising wound infection.

PMID- 11954163
TI  - Using the internet to update practice.

PMID- 11954164
TI  - An integrated care pathway for leg ulcer management.

PMID- 11954165
TI  - Aversion therapy. Ghost of gay 'sickness' haunts nursing.

PMID- 11954167
TI  - Elderly care. Diabetes time bomb ticking under services.

PMID- 11954166
TI  - Drug administration. A fatal error of judgement.

PMID- 11954168
TI  - Asylum seekers. The nurses on our doorstep.

PMID- 11954169
TI  - Why the tragedy of suicide diminishes us all.

PMID- 11954170
TI  - Ebola crisis.

PMID- 11954171
TI  - Is the word 'patient' outmoded?

PMID- 11954172
TI  - Indignity of 'dumped' bodies must never happen again.

PMID- 11954173
TI  - Embrace the vital role of immunisation.

PMID- 11954174
TI  - Nurses should not collude with spying on parents.

PMID- 11954175
TI  - Sugar-coated killer.

PMID- 11954176
TI  - Recruitment. Can the NHS make their dream come true?

PMID- 11954177
TI  - Type 2 diabetes and cardiovascular disease.

PMID- 11954178
TI  - Flu in the community: nursing management.

PMID- 11954179
TI  - Action research in rehabilitation care for older people.

PMID- 11954180
TI  - Detaining patients: a study of nurses' holding powers.

PMID- 11954181
TI  - Emergency contraception and teenage sexuality.

PMID- 11954182
TI  - Fit for practice. Part 2: Nurses' roles and skills.

PMID- 11954183
TI  - Bladder retraining.

PMID- 11954184
TI  - Alder Hey. Full extent of organ horror revealed.

PMID- 11954185
TI  - HIV/AIDS. Cuts endangering lives.

PMID- 11954186
TI  - Mental health. Inquiry clears nurse suspended after patient killed girlfriend.

PMID- 11954187
TI  - Hospital arrest. Camera hidden in nurses' shower.

PMID- 11954188
TI  - Safety at work. Violence on the increase.

PMID- 11954189
TI  - Long-term care. Scots to fund all elderly care.

PMID- 11954190
TI  - Diabetes. Treatment could end daily jabs.

PMID- 11954191
TI  - Denervation techniques.
AB  - The bladder can be denervated at several levels: centrally, at the level of the
      sacral nerves; peripherally, on the pelvic nerves; or in the bladder, by cutting
      the relevant structures, by injecting substances toxic to nerves, or by
      hyperbaric bladder distension. These procedures target the sensory or motor
      nerves to weaken or to interrupt the detrusor reflex arc. Most of the procedures
      introduced previously, e.g. bladder trans-section by open operation, endoscopic
      or transvesical phenolization, hyperbaric bladder distension, and peripheral
      denervation of the bladder, have now been abandoned. Although some of these
      techniques had a high initial success rate in abolishing detrusor overactivity
      and in controlling incontinence, the relapse rate within 18 months approached
      100%. In the early 1950s, much of the denervation surgery was performed on sacral
      roots and nerves. Nowadays, sacral de-afferentiation of the bladder by dorsal
      sacral root rhizotomy of S2-S5, using specialized techniques, either intradurally
      or at the conal level, has proved to be a very effective procedure for patients
      with spinal cord injuries and detrusor hyper-reflexia, functional low compliance
      and reflex incontinence, which cannot be managed by any other means. In
      conclusion, although in approximately 90% of patients the symptoms of an
      overactive bladder will be eliminated or improved by conservative methods of
      treatment, bladder denervation procedures still have a place in the management of
      these patients. In particular, with these procedures a low-pressure bladder
      system can be obtained and urinary continence restored in patients with complete
      suprasacral spinal cord lesions.

PMID- 11954192
TI  - Sacral neuromodulation for treatment of lower urinary tract dysfunction.
AB  - Despite initial reservations, sacral neuromodulation has begun to develop as a
      new therapeutic tool for the treatment of lower urinary tract dysfunction. It
      bridges the gap between conservative treatment options and highly invasive
      procedures, such as urinary diversion. At present, there are no clinical
      variables that can reliably predict the efficacy of neuromodulation in an
      individual patient. All patients, regardless of indication, must therefore
      undergo a test stimulation before they can be offered chronic sacral
      neuromodulation with an implanted system. Evaluations in various clinical trials
      have confirmed that sacral neuromodulation, based on unilateral sacral foramen
      electrode implantation, has statistically significant therapeutic effects
      compared to controls, in patients with urge syndromes and failure to empty. The
      patients most likely to benefit from this treatment are those with detrusor
      hyperactivity or detrusor hypo-activity. Those with pain syndromes are less
      likely to respond and to benefit from treatment. Acute and subchronic sacral
      neuromodulation are associated with very low rates of complications.
      Complications of chronic sacral neuromodulation are caused either by surgery
      related morbidity or hardware problems. Conservative treatment options should be
      exhausted before neuromodulation is considered. This rule has two purposes:
      First, it postpones surgery, with its potential morbidity, for as long as
      possible; second, the long-term efficacy of neuromodulation is still unclear and
      may be limited in some patients. A fully exploited conservative therapy, in
      combination with subsequent sacral neuromodulation, may therefore be the optimum
      way to pursue therapeutic options of relatively low invasiveness.

PMID- 11954193
TI  - Sacral neuromodulation: treatment success is not just a matter of optimal
      electrode position.

PMID- 11954194
TI  - New methods of bladder augmentation.
AB  - Gastrointestinal segments are commonly used for bladder replacement or repair.
      However, when gastrointestinal tissue is in contact with the urinary tract,
      several complications may ensue. Recent surgical approaches have relied on native
      urological tissue for reconstruction. These are based on sound surgical
      principles, allowing for the exclusion of tissue that is not urological. De
      epithelialized bowel segments, either alone or over native urothelium, have also
      been used. An experimental system of progressive dilatation for ureters and
      bladders has been proposed. This appears promising, although it has yet to be
      attempted clinically. There has been a resurgence of interest in the use of
      acellular collagen-based matrices as scaffolds for bladder regeneration;
      experimental work is currently underway. Recently, functional bladder tissue has
      been engineered using selective cell transplantation. This technique uses
      autologous cells, so avoiding rejection. Tissue is obtained from the host, the
      cells then dissociated and expanded in vitro, re-attached to a matrix and
      implanted into the same host. Clinical trials are currently being arranged. Even
      though the use of bowel for bladder tissue replacement was first proposed over
      100 years ago, it remains the gold standard, despite its associated problems. It
      is evident that urothelial-urothelial anastomoses are preferable functionally.
      Experience is currently being gained with the recent clinical and experimental
      approaches to augmentation cystoplasty. It is hoped that this will result in more
      technologies and methods for bladder augmentation.

PMID- 11954195
TI  - The changing landscape of bladder augmentation.

PMID- 11954196
TI  - Classification and treatment of functional incontinence in children.
AB  - Functional urinary incontinence in children may be caused by disturbances of the
      filling phase, the voiding phase or a combination of both. Detrusor overactivity
      may cause frequency and urgency, with or without urge incontinence. Girls present
      with symptoms of detrusor overactivity more often than boys, but sometimes other
      symptoms, e.g. urinary tract infections or constipation, prevail. Frequent
      contractions of the detrusor may cause the pelvic floor muscles to become
      overactive, resulting in staccato or fractionated voiding. When incontinence is
      the result of a voiding disorder the term 'dysfunctional voiding' is used.
      Bladder function in these children may be normal, but instability may be present.
      In children with a 'lazy' bladder, voiding occurs with no detrusor contractions,
      and postvoid residual volumes and overflow incontinence are the main
      characteristics. Diagnosis is based on the medical and voiding history, a
      physical examination, bladder diaries and uroflowmetry. The upper urinary tract
      should be evaluated in children with recurrent infections and dysfunctional
      voiding (reflux). Uroflowmetry can be combined with pelvic floor electromyography
      to detect overactivity of the pelvic floor muscles. Urodynamic studies are
      usually reserved for patients with dysfunctional voiding and those not responding
      to anticholinergic drugs. Treatment is usually a combination of 'standard
      therapy', behavioural therapy, bladder training, physiotherapy and medical
      treatment. The role of alpha-blockers needs to be evaluated further. Also,
      neuromodulation may have a place in treatment but the exact indications need to
      be defined. Clean intermittent self-catheterization is sometimes necessary in
      children with a lazy bladder and large residual volumes who do not respond to a
      more conservative approach. Future research needs to be directed towards
      improving understanding of the pathophysiology, epidemiology, classification and
      treatment modalities of functional incontinence in children.

PMID- 11954197
TI  - Overactive bladder: paediatric aspects.

PMID- 11954198
TI  - Mixed symptomatology.
AB  - Mixed symptomatology, i.e. both stress and urge incontinence, is reported by
      patients, either of their own accord or in response to a questionnaire. Our
      understanding of motor urge incontinence, detrusor instability, stress
      incontinence and sensory urge incontinence is changing. Detrusor instability is
      now known to be a urodynamic observation of uncertain clinical significance.
      Symptoms reported by patients are not equivalent to a urodynamic diagnosis but
      the problem seems to be more in the urodynamics than in the symptoms. Evidence
      shows that sensory urge incontinence and motor urge incontinence are probably
      gradations of the same condition. The relationship between stress incontinence
      and an overactive bladder is complex. For example, neither detrusor instability
      nor urge incontinence appear to adversely influence the outcome of surgical
      treatment for stress incontinence; however, this treatment does not have a good
      success rate. At present, it is not clear whether this poor outcome reflects a
      lack of efficacy of the operations used, or their application to inappropriate
      patients.

PMID- 11954199
TI  - Difficult to manage patient populations--mixed symptomatology.

PMID- 11954200
TI  - Lower urinary tract symptoms, benign prostatic obstruction and the overactive
      bladder.
AB  - Lower urinary tract symptoms (LUTS), benign prostatic obstruction (BPO), and the
      overactive bladder have increasing prevalence with age in both men and women
      (with the obvious exception). The question is, are they interrelated or
      independently related to age? The specific issue is whether BPO causes the
      overactive bladder. There are two pieces of evidence that might appear to suggest
      such a cause and effect. First, the overactive bladder is more common in men than
      in women of the same age, although physiologically, men are 5-10 years older at
      the same biological age. Second, the overactive bladder resolves in two-thirds of
      individuals after surgical interventions such as transurethral prostatectomy. The
      symptoms suggestive of an overactive bladder are the most troublesome, even
      though they may not be the most prevalent. Long-term follow-up studies with
      repeated urodynamic investigations have shown that the incidence of the
      overactive bladder and its attendant symptoms increases despite there being no
      deterioration in outlet obstruction over follow-up periods of 10 and 20 years.
      These data, and others, indicate that the situation is not as straightforward as
      some believe. The statement that 'the overactive bladder is secondary to BPO'
      cannot be made, as there are too many unanswered questions and pieces of the
      puzzle that do not fit. The overactive bladder is undoubtedly associated with
      BPO, and it leads to the most troublesome LUTS in older men. Epidemiological
      research, coupled with urodynamic evaluation, may provide further evidence. We
      also need better and more relevant models (e.g. ageing animals), together with
      further histological and other biological data before the waters become crystal
      clear.

PMID- 11954201
TI  - Pathogenesis of the overactive bladder and its attendant risk factors.

PMID- 11954202
TI  - Intractable incontinence in the elderly.
AB  - The number of people living into extreme old age is rising exponentially in the
      USA, Europe and other developed countries. Urinary incontinence is prevalent in
      this population. While many very old (age > 75 years) incontinent individuals are
      relatively healthy and respond well to various treatments, a substantial
      proportion has impaired cognitive function and impaired mobility. These
      impairments make urinary incontinence much more difficult to assess, manage and
      cure than in younger populations. Irrespective of age and disability, a basic
      assessment of incontinence should be carried out to identify potentially
      reversible causes and indications for further evaluation. The outcome of such an
      assessment may not be cure or improvement of incontinence, but better quality of
      life and the prevention of morbid and expensive medical conditions that may
      result from poorly managed incontinence. Incontinence in this population should
      generally not be considered 'intractable' until a trial of noninvasive therapy
      (i.e. behavioural and/or pharmacological) has been undertaken. Some very frail
      elderly respond well to a toileting programme such as prompted voiding, and a
      small but significant proportion benefit from the careful addition of a bladder
      relaxant drug to the toileting programme. Others, depending on their ability and
      willingness to toilet and their preferences for further treatment, may be
      candidates for surgical intervention. Pads and garments should not be used so
      that they foster dependency, or as a primary treatment until other specific
      interventions have been tried. Indwelling catheters should be used only for
      specific and well-documented indications, because of the risks of urinary tract
      infection and sepsis associated with their long-term use. The dictionary defines
      'intractable' as 'not easily relieved or cured'. In the elderly, cure for
      incontinence, and most other chronic conditions, is the exception rather than
      rule. Relief (or amelioration), improvement in function and quality of life, and
      the exclusion of treatable medical conditions that cause morbidity and expense
      when undiagnosed, are generally achievable and more important goals than complete
      cure.

PMID- 11954203
TI  - Incontinence in the elderly.

PMID- 11954204
TI  - Denervation techniques have limited applicability.

PMID- 11954205
TI  - Drug firms 'waging war' on the developing world.

PMID- 11954206
TI  - Fostering the mental health of youngsters leaving care.

PMID- 11954207
TI  - Recruiting for the future.

PMID- 11954209
TI  - Should the RCN have appointed an American as general secretary?

PMID- 11954208
TI  - Hospital design. Firm foundations.

PMID- 11954210
TI  - Running before the avalanche.

PMID- 11954211
TI  - Immunisation: productive but disruptive.

PMID- 11954212
TI  - Trying to keep body and soul together.

PMID- 11954213
TI  - AIDS hasn't gone away.

PMID- 11954214
TI  - Why nurses end up in court.

PMID- 11954216
TI  - 'The doctors saved Alex but the nurses saved me'.

PMID- 11954215
TI  - Neonatal nursing. A small beginning.

PMID- 11954217
TI  - A right to choose.

PMID- 11954218
TI  - Educational input to improve documentation skills.

PMID- 11954219
TI  - Diabetes: blood glucose monitoring.

PMID- 11954220
TI  - Better health care and learning disability.

PMID- 11954221
TI  - In-hospital resuscitation for ward nurses.

PMID- 11954222
TI  - Hypothermia--2. Rewarming patients.

PMID- 11954223
TI  - Fit for practice. Part 2.4: Scope of professional practice.

PMID- 11954224
TI  - Health visiting. Black HVs harassed by clients.

PMID- 11954225
TI  - Practice nursing. Nurses struggling to tackle obesity.

PMID- 11954226
TI  - HIV/AIDS. Man 'deliberately infected' girlfriend.

PMID- 11954227
TI  - Drug error. Child given the wrong treatment.

PMID- 11954228
TI  - Staffing levels. Call for review after deaths.

PMID- 11954229
TI  - Sexual health. Unsafe sex is on the increase.

PMID- 11954230
TI  - Long-term care nurses ignored.

PMID- 11954231
TI  - 'Paternalism' at the root of body parts nightmare.

PMID- 11954233
TI  - Financial health check. You owe us.

PMID- 11954232
TI  - Organ retention. 'I feel like I'm grieving for a second child'.

PMID- 11954234
TI  - 'People compare me to Beverly Allitt'.

PMID- 11954235
TI  - Winter of discontent.

PMID- 11954237
TI  - Covert drugs can be right for clients.

PMID- 11954236
TI  - Should nurses encourage parents to take up the MMR vaccine?

PMID- 11954238
TI  - There for the asking.

PMID- 11954239
TI  - Drug errors could be so easy to avoid.

PMID- 11954240
TI  - Where to go for help after a sharps injury.

PMID- 11954242
TI  - Don't be a slack Alice.

PMID- 11954241
TI  - The place of ART in the gallery of HIV care.

PMID- 11954243
TI  - Love, life and nursing.

PMID- 11954244
TI  - Mental health. Focus on the positive.

PMID- 11954245
TI  - Interpreting. Language matters.

PMID- 11954246
TI  - Body parts and the law.

PMID- 11954247
TI  - New therapies for the management of type 2 diabetes.

PMID- 11954249
TI  - Fit for practice. Part 2: Professionalism.

PMID- 11954248
TI  - The treatment of anogenital warts at home.

PMID- 11954250
TI  - Systems and diseases. Exploring normal anatomy and physiology. Nervous system. 6.

PMID- 11954251
TI  - Nurses wrong-footed by girl's broken leg.

PMID- 11954252
TI  - Coroner 'implores' hospitals to change cancer drug syringe.

PMID- 11954253
TI  - New family health nurses for Scotland.

PMID- 11954254
TI  - Asthma patients can be 'in control'.

PMID- 11954255
TI  - Female devices: are your patients missing out?

PMID- 11954256
TI  - A guide to female urinals.

PMID- 11954258
TI  - The camera never lies.

PMID- 11954257
TI  - Assessing fluid balance.

PMID- 11954259
TI  - Calm after the storm.

PMID- 11954260
TI  - Primary care. What price nurses' loyalty to labour?

PMID- 11954261
TI  - Heart disease. Not just a short, sharp shock.

PMID- 11954262
TI  - Learning disabilities. 'Really good news' for neglected nurses.

PMID- 11954263
TI  - Home is where the harm is.

PMID- 11954264
TI  - Time for a radical rethink.

PMID- 11954265
TI  - Is it ok to lie about your mental health when applying for a job?

PMID- 11954266
TI  - Go west for a 'can do' attitude that's a tonic.

PMID- 11954267
TI  - Myth misgiving rationale.

PMID- 11954268
TI  - Don't make it hard on yourself.

PMID- 11954269
TI  - In praise of model nurses.

PMID- 11954270
TI  - Dave, death and me.

PMID- 11954271
TI  - Targets mean nothing unless the government kicks violence into touch.

PMID- 11954272
TI  - Guidelines for preventing hospital-acquired infection.

PMID- 11954273
TI  - Standard principles for preventing HAIs.

PMID- 11954274
TI  - The nurse's role in screening for diabetic retinopathy.

PMID- 11954275
TI  - Stoma care--1(b). Cutting a template.

PMID- 11954276
TI  - Fit for practice. Part 3.4: The complexity of human interactions.

PMID- 11954277
TI  - Intensive care. Critical coverage of ICU discharge deaths.

PMID- 11954278
TI  - Men's health. The phantom menace.

PMID- 11954279
TI  - Is it time to end the mental health nurse role?

PMID- 11954287
TI  - 10 ways to improve your practice.

PMID- 11954288
TI  - Walk-in Centers. Walkin' the walk, talkin' the talk.

PMID- 11954289
TI  - Learning disabilities. Making history.

PMID- 11954290
TI  - Naming and shaming.

PMID- 11954291
TI  - Putting research into practice.

PMID- 11954292
TI  - Now you are a nurse prescriber--what should you do next?

PMID- 11954293
TI  - Maintaining an accurate fluid and electrolyte balance.

PMID- 11954294
TI  - Stoma care--6(b). Complications.

PMID- 11954295
TI  - Fit for practice. 6.2: The process of developing evidence-based practice.

PMID- 11954296
TI  - Preventing readmission in mental health.

PMID- 11954297
TI  - Here IT comes. Ready?

PMID- 11954298
TI  - Public health. No ad plan despite HIV rise.

PMID- 11954300
TI  - Clearing the smoke.

PMID- 11954301
TI  - No more secrets and lies. Interview by Helene Mulholland.

PMID- 11954302
TI  - Revival of the fittest.

PMID- 11954303
TI  - Do mental health services do more harm than good?

PMID- 11954306
TI  - At last, a patient voice with teeth.

PMID- 11954307
TI  - Is nursing a job for the boys?

PMID- 11954308
TI  - Nurses butt in.

PMID- 11954309
TI  - With this job I thee wed.

PMID- 11954310
TI  - Measuring quality in a paediatric day care unit.

PMID- 11954311
TI  - Surgical therapy for inflammatory bowel disease.

PMID- 11954312
TI  - Inappropriate placements in registered nursing homes.

PMID- 11954313
TI  - Psychiatric caring.

PMID- 11954314
TI  - Systems and diseases. Exploring normal anatomy and physiology. Nervous system. 7.

PMID- 11954315
TI  - Fit for practice. Part 3.1: Managing professional relationships.

PMID- 11954317
TI  - Anger over double HIV test.

PMID- 11954319
TI  - Your career development still decided by a postcode lottery.

PMID- 11954320
TI  - Drug errors. A brother's legacy.

PMID- 11954321
TI  - Fingers crossed and keep on puffing.

PMID- 11954322
TI  - Should the retirement age for nurses stay at 55?

PMID- 11954323
TI  - Mind is trivialising mental health.

PMID- 11954324
TI  - Nursing blueprint for elderly care.

PMID- 11954325
TI  - Dementia care. All in the mind.

PMID- 11954326
TI  - Pet therapy. Paws for thought.

PMID- 11954327
TI  - Managers must ensure that money for training is spent on grassroots nurses.

PMID- 11954328
TI  - Inflammatory bowel disease.

PMID- 11954329
TI  - Hypothermia management.

PMID- 11954330
TI  - Clinical nurse specialists: towards a definition.

PMID- 11954331
TI  - Dementia: early diagnosis is vital for best care.

PMID- 11954332
TI  - Using a tympanic thermometer.

PMID- 11954333
TI  - Fit for practice. Part 2.5: Reflection and learning.

PMID- 11954337
TI  - Clinical guidelines: can they be effective?

PMID- 11954338
TI  - Managing exudate.

PMID- 11954339
TI  - Breast -feeding. No skimming on milk in the workplace.

PMID- 11954340
TI  - Want to know how to behead yourself? Just go online.

PMID- 11954341
TI  - After the crash, the impact.

PMID- 11954342
TI  - From fossils to family planning.

PMID- 11954343
TI  - The nurses who have to iron and wash cars.

PMID- 11954344
TI  - Should free personal care be available for all older people?

PMID- 11954346
TI  - Just say no to faulty, outdated equipment.

PMID- 11954345
TI  - We're not the bad guys.

PMID- 11954347
TI  - Listen up, because it's going to be you one day.

PMID- 11954348
TI  - Fighting to be heard. Interview by Helene Mulholland.

PMID- 11954349
TI  - Hear today, gone tomorrow.

PMID- 11954350
TI  - Caring for Peggy.

PMID- 11954351
TI  - Is anybody listening?

PMID- 11954352
TI  - Hepatitis C. Why all the fuss?

PMID- 11954353
TI  - A fair share.

PMID- 11954354
TI  - Colorectal cancer.

PMID- 11954355
TI  - Facial shaving.

PMID- 11954356
TI  - Fit for practice. Part 3.2: Issues in professional relationships.

PMID- 11954357
TI  - Senior nurses. Thoroughly modern matron.

PMID- 11954358
TI  - A change for the better?

PMID- 11954359
TI  - Ode to a Nightingale.

PMID- 11954360
TI  - You're in the NHS now.

PMID- 11954361
TI  - Should HCAs be allowed to call themselves nurses?

PMID- 11954362
TI  - A failing operation.

PMID- 11954363
TI  - Oil on troubled waters?

PMID- 11954364
TI  - Getting the massage across.

PMID- 11954365
TI  - They think it's all over.

PMID- 11954366
TI  - A hot issue.

PMID- 11954367
TI  - Specialist nurses are essential to keep TB where it belongs--in the past.

PMID- 11954368
TI  - Preventing infections associated with central venous catheters.
AB  - CR-BSI is one of the most serious complications in an already seriously ill
      patient. Incorporation of these recommendations into local protocols and routine
      clinical practice will help to bring about a significant reduction in the
      incidence of CR-BSI in all NHS acute care trusts. The evidence base will be
      reviewed in 2002.

PMID- 11954369
TI  - TB-hit area has 50% specialist nurse shortfall.

PMID- 11954370
TI  - Nurse-initiated coronary thrombolysis.

PMID- 11954371
TI  - Crossing the professional boundaries.

PMID- 11954372
TI  - Stoma care--2. Emptying a drainable pouch.

PMID- 11954373
TI  - Fit for practice. Part 4.1: Changes in health care policy.

PMID- 11954374
TI  - Children's mental health nursing.

PMID- 11954375
TI  - Is nursing the dying a lost art?

PMID- 11954376
TI  - Keep modern medicine out of the death penalty.

PMID- 11954377
TI  - The end results.

PMID- 11954378
TI  - Dealing with death.

PMID- 11954379
TI  - The Feelsafe factor.

PMID- 11954380
TI  - Alternative remedies. Natural healing. Interview by David Potterton.

PMID- 11954381
TI  - Managing occlusion in central venous catheters.

PMID- 11954382
TI  - Expanding the remit of palliative care.

PMID- 11954383
TI  - NVQ training unlocks the potential of nursing auxiliaries.

PMID- 11954384
TI  - Stoma care--6(a). Complications.

PMID- 11954385
TI  - Fit for practice. 5.4: Ethics and nursing practice.

PMID- 11954389
TI  - As tough as old boots?

PMID- 11954390
TI  - Resuscitation. For nurses and patients, it's a matter of life and death.

PMID- 11954391
TI  - Is Scots 'champion' the wonder nurse?

PMID- 11954392
TI  - General election. Just what the doctors ordered.

PMID- 11954393
TI  - Quality assurance. Opportunity knocks.

PMID- 11954394
TI  - Mental health. Bringing patients back from the brink.

PMID- 11954395
TI  - Will the human genome project have any impact on nursing?

PMID- 11954396
TI  - Better by design.

PMID- 11954397
TI  - It's a fact: hospitals make you sick.

PMID- 11954398
TI  - Behind every great nurse....

PMID- 11954399
TI  - Best of both worlds.

PMID- 11954400
TI  - Wake-up call from Kate.

PMID- 11954401
TI  - Nursing is a tough enough job, without the threat of violence to contend with.

PMID- 11954402
TI  - Judgement on the road to advocacy.

PMID- 11954403
TI  - Better quality of care for UGI cancer patients.

PMID- 11954404
TI  - Community palliative care: the evolving role of Macmillan nurses.

PMID- 11954405
TI  - Practical aspects of stoma care.

PMID- 11954406
TI  - Stoma care--1(a). Cutting a template.

PMID- 11954407
TI  - Coaching for health care assistants.

PMID- 11954408
TI  - Fit for practice. Part 3.3: Health care interactions.

PMID- 11954409
TI  - Medical error. Liver transplant nurse in a coma after insulin overdose.

PMID- 11954410
TI  - Diffuse parenchymal lung disease (DPLD).

PMID- 11954411
TI  - Managing chronic obstructive pulmonary disease at home.

PMID- 11954412
TI  - The use of management plans in patients' control of asthma.

PMID- 11954413
TI  - Sexual health and the respiratory patient.

PMID- 11954417
TI  - Nurses are caught in the crossfire.

PMID- 11954418
TI  - Would tougher sentences deter violence against health staff?

PMID- 11954427
TI  - How to make yourself just the job.

PMID- 11954426
TI  - Minorities need role models, not quotas.

PMID- 11954428
TI  - How to shine at the interview.

PMID- 11954429
TI  - Demystifying practice development.

PMID- 11954430
TI  - Making the best use of overseas recruits' skills.

PMID- 11954431
TI  - Empowerment in policy and practice.

PMID- 11954433
TI  - Systems and diseases. Nervous system 10. The pathophysiology of intracranial
      hemorrhage and its management.

PMID- 11954432
TI  - A 40-year-old man was recently admitted with progressive supranuclear palsy for
      two weeks respite care.

PMID- 11954434
TI  - Fit for practice. 6.1: What is evidence-based practice?

PMID- 11954435
TI  - Hand-washing key to food safety.

PMID- 11954436
TI  - Campylobacter: diagnosis, treatment and prevention.

PMID- 11954437
TI  - Scabies.

PMID- 11954438
TI  - A flexible approach to methicillin-resistant Staphylococcus aureus (MRSA).

PMID- 11954439
TI  - What health care assistants know about clean hands.

PMID- 11954443
TI  - Is there a nurse in the house?

PMID- 11954442
TI  - Same old story about elderly care.

PMID- 11954444
TI  - Foot-and-mouth disease. 'We're crying with them'.

PMID- 11954445
TI  - Time to swing the mood.

PMID- 11954446
TI  - This year's slogan? I can't believe it's not better.

PMID- 11954447
TI  - Is rationing the only way forward for the NHS?

PMID- 11954448
TI  - Don't panic.

PMID- 11954449
TI  - A short history of PREParation.

PMID- 11954450
TI  - Cured but still in need of care.

PMID- 11954451
TI  - Kettles strictly forbidden.

PMID- 11954452
TI  - We've got the service framework, now nurses need proper training in elderly care.

PMID- 11954453
TI  - Preventing infections from short-term indwelling catheters.

PMID- 11954454
TI  - A development programme for newly qualified staff nurses.

PMID- 11954455
TI  - Life after stroke: Sam's story.

PMID- 11954456
TI  - Teaching opportunities in nursing homes.

PMID- 11954457
TI  - Systems and diseases. Exploring normal anatomy and physiology. Nervous system. 8.

PMID- 11954458
TI  - Fit for practice. Part 3.5: The wider context of health care relationships.

PMID- 11954459
TI  - Promoting healing in static wounds.

PMID- 11954460
TI  - Clinical governance and tissue viability.

PMID- 11954461
TI  - Treating children's wound pain in the community.

PMID- 11954462
TI  - Managing exudate.

PMID- 11954464
TI  - Sharps safety. Solving the needlestick nightmare.

PMID- 11954465
TI  - Sexual health. Is nurse's sex education growing and changing?

PMID- 11954466
TI  - International nursing. Wish you were here?

PMID- 11954467
TI  - Are nurses ready to prescribe without a doctor's endorsement?

PMID- 11954468
TI  - In the jaws of privatisation.

PMID- 11954477
TI  - Doctors on the cheap?

PMID- 11954478
TI  - Finding the right words.

PMID- 11954479
TI  - Relocation. Where the grass is always greener.

PMID- 11954480
TI  - Dramatic improvement in COPD patient care in nurse-led clinic.

PMID- 11954481
TI  - First-rate care for women with problems in pregnancy.

PMID- 11954484
TI  - Now you are a nurse prescriber--what next?

PMID- 11954485
TI  - How patients can contribute to nurses' education.

PMID- 11954486
TI  - Practical procedures for nurses. Blood transfusion--1.

PMID- 11954487
TI  - Fit for practice. 6.3: Care pathways.

PMID- 11954488
TI  - Welcome to a valuable code.

PMID- 11954489
TI  - Traumatic wounds: nursing assessment and management.

PMID- 11954490
TI  - Ultrasound therapy.

PMID- 11954493
TI  - Leg ulceration in rheumatoid arthritis.

PMID- 11954494
TI  - A protocol for care of skeletal pin sites.

PMID- 11954495
TI  - Implementing best practice in pressure ulcer prevention.

PMID- 11954497
TI  - Out of Africa.

PMID- 11954498
TI  - New streamlined look for Scottish services.

PMID- 11954499
TI  - Is being a student nurse harder now than ever before?

PMID- 11954501
TI  - And how to survive your students.

PMID- 11954500
TI  - How to survive as a student.

PMID- 11954502
TI  - Mental health. Enough respect.

PMID- 11954503
TI  - Backs against the wall.

PMID- 11954504
TI  - A telephone link line for thoracic surgery patients.

PMID- 11954505
TI  - Health promotion priorities of people with HIV.

PMID- 11954506
TI  - Clinical governance and you.

PMID- 11954508
TI  - Raising the profile of stroke care.

PMID- 11954507
TI  - Blocked urinary catheters: nurses' preventive role.

PMID- 11954509
TI  - Care orders are 'unenforceable'.

PMID- 11954510
TI  - Measuring lying and standing BP--1.

PMID- 11954511
TI  - Smoking. Few quitters in elderly care.

PMID- 11954512
TI  - Winter pressures. Tis the season to be ready.

PMID- 11954513
TI  - Research. From ivory towers to brass tacks.

PMID- 11954514
TI  - Mental health. This time next year....

PMID- 11954516
TI  - Ignorance is not bliss.

PMID- 11954515
TI  - Is the notion of free health care out of date?

PMID- 11954517
TI  - Talking about the same old care?

PMID- 11954518
TI  - Forced out of NHS by stress of assignments.

PMID- 11954519
TI  - Patient dignity equals privacy.

PMID- 11954520
TI  - GPs' poor relations.

PMID- 11954521
TI  - Life support for television.

PMID- 11954522
TI  - Fed up with poor food.

PMID- 11954523
TI  - A load of junk.

PMID- 11954524
TI  - Nine months of dribbling.

PMID- 11954525
TI  - On call should not mean nurses working a double shift on paltry pay.

PMID- 11954526
TI  - Nurses must help to build the future.

PMID- 11954527
TI  - Nurse-friendly integrated care pathways.

PMID- 11954528
TI  - The gift of life.

PMID- 11954529
TI  - Communicating with unconscious patients.

PMID- 11954530
TI  - Reality orientation for dementia.

PMID- 11954531
TI  - Don't hold back on restraint.

PMID- 11954532
TI  - The hepatitis viruses. 2. Testing for hepatitis, treatment and prevention.

PMID- 11954533
TI  - Psychosocial rehabilitation after burn injuries.

PMID- 11954534
TI  - Intermittent sequential compression therapy.

PMID- 11954535
TI  - Traumatic wounds: the management of superficial and partial thickness burns.

PMID- 11954536
TI  - Psychological aspects of wound healing.

PMID- 11954537
TI  - Demystifying systematic reviews.

PMID- 11954538
TI  - Wound care practice in nursing homes.
AB  - The majority of nursing homes were using wound assessment charts, pressure ulcer
      risk calculators and pressure ulcer grading systems, but it was not possible to
      assess whether they were being used properly; From the information collected,
      staff appeared to be using wound care products in appropriate situations; All
      respondents were eager to learn and suggested a variety of areas for future
      education; Pressure-relieving equipment available in the homes was inadequate and
      where available staff were not always certain of its correct use; There appeared
      to be confusion regarding cleansing and managing infected wounds. Subsequent
      developments to the service include formulation of a wound care course, the
      development of a link nurse system to promote dissemination of information,
      pressure ulcer prevalence monitoring and the use of a wound management product
      formulary.

PMID- 11954539
TI  - No good deed will go unpunished.

PMID- 11954541
TI  - [Stasis dermatitis].

PMID- 11954542
TI  - [Posterior reversible encephalopathy syndrome].

PMID- 11954543
TI  - Low serum cholesterol is correlated to suicidality in a Korean sample.
AB  - OBJECTIVE: The aim of this study was to examine further the association between
      low total serum cholesterol and suicidal behaviour. METHOD: We measured the serum
      cholesterol levels in 231 patients admitted to an emergency room following a
      suicide attempt, in 231 age-,sex- and diagnosis-matched non-suicidal psychiatric
      controls, and in 231 age- and sex-matched normal controls. The suicide attempt
      patients were divided into five grades according to the degree of injury.
      RESULTS: The mean total cholesterol level of the suicide attempt patients was
      significantly lower than that of the psychiatric and normal controls. When the
      suicide attempt patients and non-suicidal psychiatric controls were divided by
      diagnosis, this significant relationship held true for major depressive disorders
      and personality disorders, but not for schizophrenia and bipolar disorders.
      Cholesterol level and the severity of suicide attempt were inversely correlated.
      CONCLUSION: The results suggest that cholesterol level may serve as a marker for
      suicide risk. Possible explanations are discussed.

PMID- 11954544
TI  - Longitudinal course of salivary cortisol in post-traumatic stress disorder.
AB  - OBJECTIVE: In chronic post-traumatic stress disorder (PTSD) lowered cortisol
      secretion and hypersuppression to dexamethasone has been described repeatedly.
      However, so far no longitudinal data on the natural course or on the effect of
      therapy are available. METHOD: We measured basal and post-dexamethasone morning
      salivary cortisol in a drug-free patient with chronic PTSD (DSM-IV) monthly for
      nearly 2 years and assessed PTSD and depressive symptoms. RESULTS: Salivary
      cortisol decreased dramatically 3 months after the traumatic event and in the
      further course showed an inverse relation to fluctuating but gradually improving
      PTSD symptoms. Post-dexa-methasone cortisol was suppressed below the detection
      limit early after trauma and rose again more than 1 year post-trauma. CONCLUSION:
      Both the potential renormalization of low cortisol levels in improving chronic
      PTSD and the putative vulnerability to develop PTSD in subjects with increased
      dexamethasone suppression need further research.

PMID- 11954545
TI  - Eukaryotic glycosyltransferases: cysteines and disulfides.
AB  - Significant progress has been made in discovering and cloning a host of
      eukaryotic glycosyltransferases, demonstrating the intricacy and complexity of
      protein and lipid glycosylation. The availability of their predicted amino acid
      sequences extended our insights into the structure/function aspects of this
      family of proteins. However, our knowledge of their three-dimensional structures
      and how structure gives rise to substrate binding and specificity is still
      limited. Glycosyltransferase X-ray crystal structures have begun to provide
      significant information on a limited number of enzymes. To date, only three
      eukaryotic glycosyltransferase crystal structures have been solved, and all of
      them are for enzymes that utilize a UDP-sugar. One of the important structural
      elements of a protein is its disulfide bonds. These covalent interactions place
      conformational constraints on the overall protein structure,providing some
      important structural information. In this letter, we outline our current
      understanding of the free Cys residues and disulfide bonds in eukaryotic
      glycosyltransferases and discuss some of the important outcomes of these
      findings.

PMID- 11954547
TI  - Noble purpose gone awry. 1986 patient antidumping law under review.

PMID- 11954546
TI  - Mother-bingo bonding: screening for gambling addiction in the neonatal intensive
      care unit.
AB  - As the prevalence of gambling increases in society, problem or pathologic
      gambling in new mothers may interfere with the bonding process as well as with
      infant and child care. Although neonatal nurses routinely screen for maternal
      addictions to substances such as alcohol, cocaine, and heroin, they are less
      likely to be alerted to signs of gambling addiction in new parents. This article
      presents a case study of a mother with a bingo preoccupation, provides neonatal
      nurses with an overview of problem and pathologic gambling, presents brief
      interview questions and a standardized screening tool for assessing gambling
      problems in parents, and suggests areas for intervention.

PMID- 11954548
TI  - A case presentation. Metastatic pheochromocytoma.

PMID- 11954550
TI  - A novel gene is disrupted at a 14q13 breakpoint of t(2;14) in a patient with
      mirror-image polydactyly of hands and feet.
AB  - Mirror-image polydactyly of hands and feet (MIP) is a very rare congenital
      anomaly characterized by mirror-image duplication of digits. To isolate the gene
      responsible for MIP, we performed translocation breakpoint cloning from an MIP
      patient with t(2;14)(p23.3;q13). We isolated a good candidate gene for MIP that
      was disrupted by the translocation of the patient. We had previously con structed
      a 1.2-megabase bacterial artificial chromosome (BAC)/P1-derived artificial
      chromosome (PAC) contig covering the 14q13 breakpoint of t(2;14)(p23.3;q13). From
      a 500-kb segment consisting of seven BAC/PAC clones in the contig, we isolated a
      novel gene (the mirror-image polydactyly 1 gene, designated as MIPOL1, GenBank
      Accession No. AY059470), in addition to the hepatocyte nuclear factor 3 alpha
      gene (HNF3A, GenBank Accession No. XM 007360). MIPOL1 spans about 350kb,
      comprises 15 exons, and encodes 442 amino acids. Northern blot analysis revealed
      that MIPOL1 expression is definite but very weak in adult heart, liver, skeletal
      muscle, kidney, and pancreas, and in fetal kidney. In view of the genome sequence
      and the contig map constructed, the 14q13 breakpoint of the patient was
      identified as located in intron 11 of MIPOL1, indicating that the gene was
      disrupted by the translocation, and that the breakage resulted in MIPOL1 protein
      truncation. Whole-mount in situ hybridization in mouse resulted in mouse Mipol1
      signals all over E10.5-E13.5 mouse embryos. Two other unrelated patients with
      limb anomalies similar to MIP were subjected to mutation analysis of MIPOL1, but
      none had any mutations. We then isolated BAC clones from the other breakpoint,
      2p23.3. A search for genes and expressed sequence tags in a more than 300-kb
      region around the 2p23.3 breakpoint found only the neuroblastoma-amplified
      protein gene (NAG, GenBank Accession No. NM 015909), which is located at least
      50kb centromeric to the breakpoint and is not likely to be related to MIP. MIPOL1
      is a good candidate gene for the MIP type of anomaly.

PMID- 11954549
TI  - Effects of exogenous glucose on survival and infectivity of Schistosoma mansoni
      cercariae.
AB  - The effects of exogenous glucose in artificial spring water (ASW) were studied on
      the survival and infectivity of Schistosoma mansoni cercariae. The mean percent
      survival of cercariae maintained in 1% glucose in ASW for 36 and 48 hr was
      significantly greater than that of cercariae maintained identically in ASW.
      Cercariae maintained in ASW with or without glucose for 24 hr, fixed in neutral
      buffered formalin, and stained in Oil Red O, showed an accumulation of neutral
      lipid in the tail. Cercariae maintained as described above and stained in
      periodic acid-Schiff exhibited depleted glycogen, mainly from the tail. Cercariae
      maintained in ASW with glucose for 24 hr did not resynthesize glycogen. Cercariae
      maintained in ASW with glucose for 24 hr were as capable of infecting male
      FVBN202 mice as were freshly emerged cercariae, and increased the percent of worm
      recovery. Exogeneous glucose added to ASW prolonged the survival of S. mansoni
      cercariae and increased infectivity in terms of worm recovery.

PMID- 11954554
TI  - [A new in vitro test to simulate gastric absorption of copper, lead, tin and zinc
      from polluted soils].
AB  - Metals in polluted soils can be ingested by young children and cause toxicity
      through gastro-intestinal absorption. Very few tests are used to evaluate the
      gastric absorption of metals from polluted soils. The Toxicity Characteristics
      Leaching Procedure (TCLP) of the Environmental Protection Agency of the United
      States is indirectly used as usually no action is taken on a polluted soil if
      lead is less than 5 mg l(-1) in the test. This paper presents a new In vitro
      simple screening test to detect soils polluted by metals which can cause gastric
      absorption. The gastric juice simulation test (GJST) is based on the chemistry of
      the stomach. The TCLP and the GJST has been applied to six different size
      fractions of 5 soils. Lead carbonate was the main form of lead pollution. Lead
      oxide, lead silicate, lead phosphate and PbaSnbOc(CO3)d, PbaTibOc(CO3)d and
      PbaCrbOc were also present. Copper is mainly found as elemental copper partly
      carbonated while zinc is as zinc oxide or carbonate. Tin is usually associated
      with iron alloy or oxide or in PbaSnbOc(CO3)d. The percentage of the surface
      occupied by a polluting phase is higher in small particles. The proportion of
      particles for which pollution is located near the surface of the particle is more
      important for small particles. The GJST leaches more copper, lead and zinc than
      the TCLP, particularly on small size fractions. Inorganic tin is not solubilised
      by the TCLP or the GJST. The percentage of metal leached from small particles is
      very important with the GJST, but not with the TCLP. The pH 5 of the TCLP is too
      high to solubilise much metals and is not a good test to evaluate polluted soils
      if gastric absorption is to be considered. For two soils out of five, the TCLP
      didn't detect problematic soils as detected with the Integrated Exposure Uptake
      Biokinetic model of the USEPA. The GJST detected all the problematic soils and is
      better to evaluate the chemical solubility of metals in the gastric environment.
      The GJST better represents the stomach environment (Cl-, pH 2, T = 37 degrees C).
      The GJST appears to be a good test to detect metal contaminated soils.

PMID- 11954555
TI  - Impact of a simple intervention to increase primary care provider recognition of
      patient referral concerns.
AB  - OBJECTIVE: To determine whether a brief previsit questionnaire about referral
      concerns can improve primary care provider (PCP) recognition of patient concerns
      and satisfaction with care. DESIGN: Sequential prospective study in the internal
      medicine clinic of an academic medical center providing primary care to patients
      enrolled in a gatekeeper-model managed care plan. PARTICIPANTS AND METHODS:
      Twelve faculty internists serving as PCPs for 1495 consecutive patient visits.
      Patients were given a previsit questionnaire asking about referral need and
      rationale and a postvisit questionnaire asking about discussion of referral
      concern and visit satisfaction. Providers were given a postvisit questionnaire
      asking whether a referral was discussed and made and about visit satisfaction. In
      the control phase, patient previsit questionnaires remained confidential, whereas
      in the intervention phase PCPs were shown the previsit questionnaires at the time
      of encounter. RESULTS: The intervention significantly increased PCP referral
      recognition from 61% to 81% (P < .001) and was associated with increased visit
      satisfaction (P = .05). Satisfaction of PCPs with the referral discussion,
      overall rate of referral, and visit duration were not affected by the
      intervention. CONCLUSIONS: Using a brief previsit questionnaire about patient
      referral concerns increases PCP recognition of such concerns. The intervention
      does not adversely affect PCP satisfaction with the referral discussion or the
      overall referral rate and may enhance patient visit satisfaction.

PMID- 11954556
TI  - Neural coding and the basic law of psychophysics.
AB  - There have been three main ideas about the basic law of psychophysics. In 1860,
      Fechner used Weber's law to infer that the subjective sense of intensity is
      related to the physical intensity of a stimulus by a logarithmic function (the
      Weber-Fechner law). A hundred years later, Stevens refuted Fechner's law by
      showing that direct reports of subjective intensity are related to the physical
      intensity of stimuli by a power law. MacKay soon showed, however, that the
      logarithmic and power laws are indistinguishable without examining the underlying
      neural mechanisms. Mountcastle and his colleagues did so, and, on the basis of
      transducer functions obeying power laws, inferred that subjective intensity must
      be related linearly to the neural coding measure on which it is based. In this
      review, we discuss these issues and we review a series of studies aimed at the
      neural mechanisms of a very complex form of subjective experience-the experience
      of roughness produced by a textured surface. The results, which are independent
      of any assumptions about the form of the psychophysical law, support the idea
      that the basic law of psychophysics is linearity between subjective experience
      and the neural activity on which it is based.

PMID- 11954557
TI  - Protein kinase signal transduction cascades in mammalian associative
      conditioning.
AB  - One of the most intriguing and intensely studied questions facing contemporary
      neuroscientists involves the elucidation of the physiological mechanisms that
      underlie learning and memory. Recent advances have given us a much more detailed
      understanding of the signal transduction mechanisms subserving learning in the
      intact animal. One fact that has become clear is that activation of protein
      kinases and phosphorylation of their downstream effectors play a critical role.
      Four protein kinase cascades have garnered considerable attention in the study of
      information storage at both the synaptic and behavioral levels: Ca++/phospholipid
      dependent protein kinase (PKC), Ca++/calmodulin-dependent protein kinase II
      (CaMKII), cAMP-dependent protein kinase (PKA), and extracellular signal-regulated
      kinase (ERK). This review will concentrate on studies of two behavioral tasks,
      conditioned fear and conditioned taste aversion, that provide evidence for the
      involvement of these kinase systems in associative learning. The authors will
      also examine a number of potential kinase substrates and how each could
      participate in the formation of long-term memories.

PMID- 11954558
TI  - Electrodermal responses: what happens in the brain.
AB  - Electrodermal activity (EDA) is now the preferred term for changes in electrical
      conductance of the skin, including phasic changes that have been referred to as
      galvanic skin responses (GSR), that result from sympathetic neuronal activity.
      EDA is a sensitive psychophysiological index of changes in autonomic sympathetic
      arousal that are integrated with emotional and cognitive states. Until recently
      there was little direct knowledge of brain mechanisms governing generation and
      control of EDA in humans. However, studies of patients with discrete brain
      lesions and, more recently, functional imaging techniques have clarified the
      contribution of brain regions implicated in emotion, attention, and cognition to
      peripheral EDA responses. Moreover, such studies enable an understanding of
      mechanisms by which states of bodily arousal, indexed by EDA, influence cognition
      and bias motivational behavior.

PMID- 11954559
TI  - Developmental changes in ionotropic glutamate receptors: lessons from hippocampal
      synapses.
AB  - Glutamatergic synapses are the primary source of excitatory transmission in the
      central nervous system (CNS), and their formation is critical in the
      establishment of neuronal connections. The refinement of these connections occurs
      during development and also it is postulated during learning and memory. Recent
      progress in understanding the molecular components of synaptic junctions,
      together with advances in imaging techniques, has started to offer new insights
      into the development of excitatory synapses. Studies performed on low-density
      primary neuronal cultures have enabled dissection of the temporal sequence of
      events, which have lead to the differentiation of pre- and postsynaptic
      components. A central feature of the development of excitatory synapses is the
      accumulation of glutamatergic receptors (GluRs) at the postsynaptic site. These
      receptors need to be localized and fixed opposite nerve terminals that release
      glutamate. But for this to occur, neurons require intracellular anchoring
      molecules, as well as mechanisms that ensure the efficient turnover and transport
      of receptor proteins. This review focuses on some of the developmental changes
      observed in the subcellular distribution and molecular organization of AMPA and
      NMDA type ionotropic GluRs (iGluRs), which mediate the majority of fast
      excitatory neurotransmission in the CNS.

PMID- 11954561
TI  - Plasticity of the visual cortex after injury: what's different about the young
      brain?
AB  - The repercussions of localized injury of the cerebral cortex in young brains
      differ from the repercussions triggered by equivalent damage of the mature brain.
      In the young brain, some distant neurons are more vulnerable to the lesion,
      whereas others survive and expand their projections to bypass damaged and
      degenerated structures. The net result is sparing of neural processing and
      behaviors. This article summarizes both the modifications in visual pathways
      resulting from visual cortex lesions sustained early in life and the neural and
      behavioral processes that are spared or permanently impaired. Experiments using
      reversible deactivation show that at least two highly localizable functions of
      normal cerebral cortex are remapped across the cortical surface as a result of an
      early lesion of the primary visual cortex. Moreover, the redistributions have
      spread the essential neural operations underlying orienting behavior from the
      visual parietal cortex to a normally functionally distinct type of cortex in the
      visual temporal system, and in the opposite direction for complex-pattern
      recognition. Similar functional reorganizations may underlie sparing of neural
      processes and behavior following early lesions in other cerebral systems, and
      these other systems may respond well to emerging therapeutic strategies designed
      to enhance the sparing of functions.

PMID- 11954563
TI  - Regulation of the cell cycle in normal and pathological glia.
AB  - Precise regulation of the glial cell cycle is essential during nervous system
      development and in response to injury, whereas disruption of cell cycle control
      is associated with malignant glial tumors and other nervous system diseases. The
      Ras signaling pathway plays a central role in regulating the mammalian cell
      cycle, and uncontrolled Ras signaling has been implicated in a wide range of
      human cancers, including malignant gliomas. Recent studies in glia have
      demonstrated that activation of Ras can either induce or inhibit proliferation
      through complex interactions among downstream signaling pathways impinging on
      cell cycle regulatory proteins. Studies in Schwann cells have begun to delineate
      the pathways by which Ras regulates the cell cycle in normal and pathological
      glia, and have identified promising targets for therapeutic intervention in the
      treatment of PNS and CNS malignant glial tumors.

PMID- 11954562
TI  - Glutamate and the presynaptic control of spinal sensory transmission.
AB  - Sensory neurons, in particular the small- and medium-diameter cells that sense
      painful stimuli, express both ionotropic and metabotropic glutamate receptors,
      which may regulate transmission between sensory neurons and their targets in the
      spinal cord dorsal horn. Although the roles that these receptors play in normal
      physiology are not completely understood, recent work has provided strong
      evidence for their ability to modulate transmitter release from primary afferent
      terminals.

PMID- 11954560
TI  - Epilepsy as an example of neural plasticity.
AB  - Epilepsy is a devastating disease affecting more than 1% of the population. Yet,
      if one considers the neurobiological substrates of this disease, what is revealed
      is an array of phenomenon that exemplify the remarkable capacity for the brain to
      change its basic structure and function, that is, neural plasticity. Some of
      these alterations are transient and merely impressive for their extent, or for
      their robust nature across animal models and human epilepsy. Others are notable
      for their persistence, often enduring for months or years. As an example, the
      dentate gyrus, and specifically the principal cell of the dentate gyrus, the
      granule cell, is highlighted. This area of the brain and this particular cell
      type, for reasons that are currently unclear, hold an uncanny capacity to change
      after seizures. For those interested in plasticity, it is suggested that perhaps
      the best examples for studying plasticity lie in the field of epilepsy.

PMID- 11954564
TI  - Do you know your brain? A survey on public neuroscience literacy at the closing
      of the decade of the brain.
AB  - What does the public know about the developments offered by brain research? What
      factors influence public neuroscience literacy? What issues need to be emphasized
      to the public? To address these questions, a survey was conducted using a
      questionnaire with 95 assertions, answered by indicating yes, no, or I don't
      know. The opinions of 35 senior neuroscientists and 2158 members of the public of
      Rio de Janeiro were heard on issues such as the mind-brain relationship, the
      senses, learning, and memory. The incidence of "correct" answers among the public
      improved the most with schooling, followed by reading of popular science
      magazines and of newspapers. An analysis of the responses to each assertion
      revealed which themes are well- or poorly known to the public. The results attest
      for the importance of popular scientific communication and indicate issues on
      which communication efforts should be concentrated in order to increase public
      awareness about the brain.

PMID- 11954565
TI  - A human genome diversity cell line panel.

PMID- 11954566
TI  - Trees, homologs, and poisons.

PMID- 11954567
TI  - Stocking the stacks.

PMID- 11954568
TI  - Italy's annual AIDS budget appropriation.

PMID- 11954569
TI  - A "water" model for nuclei still holds water.

PMID- 11954570
TI  - Biotech poetry.

PMID- 11954571
TI  - The mythologizing of psychoanalytic history: deception and self-deception in
      Freud's accounts of the seduction theory episode.

PMID- 11954572
TI  - The factors of insanities: J. Hughlings Jackson. Classic Text No. 47.

PMID- 11954573
TI  - Due process in Medicare appeals: a primer.
AB  - This brief is the first of a two-part series on Medicare appeals. The first
      article discusses appeal rights generally--the importance of notice, grounded in
      the right to be heard, when someone's statutory rights are denied, reduced or
      terminated. Next month we will focus on the specifics of beneficiary appeal
      rights.

PMID- 11954574
TI  - Family problems.

PMID- 11954575
TI  - A good idea whose time will come.

PMID- 11954576
TI  - No consensus worldwide.

PMID- 11954577
TI  - Family covenants and confidentiality within families.

PMID- 11954578
TI  - The family covenant: a flawed response to the dilemmas of genetic testing.

PMID- 11954580
TI  - Family covenant: considerations of trust.

PMID- 11954579
TI  - To tell or not to tell: mandating disclosure of genetic testing results.

PMID- 11954581
TI  - Confidentiality in genetic testing.

PMID- 11954582
TI  - The family: organic and mechanistic solidarity.

PMID- 11954583
TI  - The myth of the nuclear family.

PMID- 11954584
TI  - Feasibility of the family-centered model for genetic testing.

PMID- 11954585
TI  - Confidentiality, genetic information, and the physician-patient relationship.

PMID- 11954586
TI  - Family physicians and the family covenant model's usefulness in solving genetic
      testing conflicts.

PMID- 11954588
TI  - Duties vs. decency.

PMID- 11954587
TI  - The family covenant and genetic testing.
AB  - The physician-patient relationship has changed over the last several decades,
      requiring a systematic reevaluation of the competing demands of patients,
      physicians, and families. In the era of genetic testing, using a model of patient
      care known as the family covenant may prove effective in accounting for these
      demands. The family covenant articulates the roles of the physician, patient, and
      the family prior to genetic testing, as the participants consensually define
      them. The initial argument defines the boundaries of autonomy and benefit for all
      participating family members. The physician may then serve as a facilitator in
      the relationship, working with all parties in resolving potential conflicts
      regarding genetic information. The family covenant promotes a fuller discussion
      of the competing ethical claims that may come to bear after genetic test results
      are received.

PMID- 11954589
TI  - Clinical ethics and family morality.

PMID- 11954590
TI  - Why not grant primacy to the family?

PMID- 11954591
TI  - Genetics and confidentiality.

PMID- 11954592
TI  - Disability: an agenda for bioethics.
AB  - Contemporary bioethics has been somewhat skewed by its focus on high-tech
      medicine and the resulting development of ethical frameworks based on an acute
      care model of healthcare. Research and scholarship in bioethics have payed only
      cursory attention to ethical issues related to disability. I argue that bioethics
      should concern itself with the full range of theoretical and practical issues
      related to disability. This encounter with the disability community will enrich
      bioethics and, potentially, society as well. I suggest a number of items that the
      bioethics agenda should include, such as the development of a casuistry of the
      right to healthcare and to community integration and an advocacy role in
      fostering an understanding among the public and policy makers of the need to
      reform research and treatment related to disability.

PMID- 11954593
TI  - Disability? Long on the agenda for some bioethicists.

PMID- 11954594
TI  - The concept of disability in bioethics: theoretical and clinical issues.

PMID- 11954595
TI  - Help wanted: entrepreneurs needed to serve bioethics' outsiders.

PMID- 11954596
TI  - Disability studies and bioethics: a comment on Kuczewski.

PMID- 11954597
TI  - Beyond disability: bioethics and patient advocacy.

PMID- 11954598
TI  - Some reflections on disability and bioethics.

PMID- 11954599
TI  - Disability matters: differences and rights.

PMID- 11954600
TI  - How long has this been going on? Disability issues, disability studies, and
      bioethics.

PMID- 11954601
TI  - Response to Mark Kuczewski.

PMID- 11954602
TI  - A neutral ethical framework for understanding the role of disability in the life
      cycle.

PMID- 11954603
TI  - Bioethics and disability: what's health got to do with it?

PMID- 11954604
TI  - Rethinking anger and advocacy in bioethics.

PMID- 11954605
TI  - Disability: societal responses to difference and interdisciplinary interventions
      by bioethicists.

PMID- 11954606
TI  - Disability and bioethics: removing barriers to understanding and setting the
      agenda for a new conversation.

PMID- 11954607
TI  - History precedes ethics.

PMID- 11954608
TI  - The making of a Calvinist chemist: Herman Boerhaave, God, fire, and truth.

PMID- 11954609
TI  - William Arthur Smeaton: an appreciation.

PMID- 11954610
TI  - Alchemical reproduction and the career of Anna Maria Zieglerin.

PMID- 11954611
TI  - Marie Meurdrac: Paracelsian chemist and feminist.

PMID- 11954612
TI  - Jesuits and alchemy in the early seventeenth century: Father Johannes Roberti and
      the weapon-slave controversy.

PMID- 11954613
TI  - The variance of rural small-town hospitals' financial performance.
AB  - The profitability of rural small-town hospitals varies widely. Some are
      consistently profitable; others generate significant losses. This Policy Brief
      provides insights into why some rural small-town hospitals are financially
      successful and others struggle with persistent financial difficulties. Our
      analysis of Medicare cost report data reveals that financial difficulties are
      most likely in hospitals with fewer than 1000 admissions. Interviews with
      hospital administrators at selected hospitals indicate that bad debts, poor
      physician relations, and broad missions also may contribute to some hospitals'
      financial difficulties.

PMID- 11954614
TI  - [Quebec's physicians, infant mortality and nationalist politics, 1910-1940].
AB  - This article analyzes the discourse of a Quebecois medical elite, comprising
      primarily public health physicians and pediatricians, concerning infant mortality
      between 1910 and 1940. It emphasizes its similarities with nationalist discourse,
      and the fact that nationalist ideology provided doctors with arguments to justify
      the staggeringly high infant mortality rate experienced by their compatriots and
      encouraged them to glorify the high birthrate of French Canadians. According to
      the medico-nationalist discourse, the high birthrate (or "Revanche des berceaux")
      would even have been an obstacle to their struggle against infant mortality (or
      their "Veillee"). The legendary fecundity of French-Canadian women, a myth that
      is historically questionable, could thus explain, at least partially, the fact
      that public health measures adopted in Quebec during this period were less
      stringent than in Ontario, the "sister province" that Quebec's hygienists took
      nonetheless as their point of reference.

PMID- 11954615
TI  - No more surprising than a broken pitcher? Maternal and child health in the early
      years of the Pan American Sanitary Bureau.
AB  - The priorities and activities of international health organizations have
      historically been determined at the metropolitan level or through a confluence of
      central and local interests. The case of maternal and child health and the Pan
      American Sanitary Bureau during the first half of the 20th century demonstrates a
      different phenomenon. Rather than sparking interest and actions in maternal and
      child health in Latin America, the PASB ignored this area even though the agency
      was repeatedly urged by numerous countries in the region over several decades to
      provide support. This article begins with an examination of the emergence of
      maternal and child health circa 1900 in Europe, North America, and Latin America,
      identifying political, demographic, ideological, economic, and cultural
      commonalities and differences in these regions. We then turn to the PASB's early
      history and modus operandi, the pressure exerted by Latin American countries upon
      the PASB to pay attention to maternal and child health, and the Bureau's
      unwillingness to work in this area. Next we explore concomitant developments in
      maternal and child health and eugenics within Latin America in the 1920s and
      1930s and the PASB's first steps in this area. Finally we discuss the conflict
      over the PASB's role in maternal and child health on several dimensions: as a
      manifestation of differing cultural priorities in the U.S. and Latin America; as
      a question of struggle for organizational power within the PASB; and as part of a
      richer understanding of the diffusion of early 20th-century public health and
      medical practices.

PMID- 11954617
TI  - The spotlight on children.

PMID- 11954618
TI  - Race, class, and health: school medical inspection and "healthy" children in
      British Columbia, 1890-1930.
AB  - School medical inspection provides a window on the construction of "healthy"
      children in British Columbia over the turn of the 20th century. Public health
      reformers, doctors, teachers, and school nurses encouraged children and their
      parents to conform to a particular model of healthy living. This paper argues
      that this model, reflecting Anglo-Celtic, middle-class, and urban sensibilities,
      pathologized children and families unable or unwilling to conform to this
      powerful social ideal. Far form simply signaling the triumph of sanitary science,
      school medical inspection was a powerful means of legitimizing existing relations
      of power and confirming social boundaries.

PMID- 11954616
TI  - [The medicalizing of mothers and children in Colonial Vietnam, 1860-1939].
AB  - Almost nothing has been written about the history of maternal and child care in
      South East Asia. The issue however has a great amount of interest. For instance,
      French Indochina under colonial rule (1860-1954) experienced significant
      advancements in both areas. Writing their history helps to better understand the
      international dissemination of medical intervention towards pregnant women and
      their children and some of the movement's national characteristics. Maternal and
      child care rapidly became the only area within the health policy Indochina
      received before and after the establishment of an official health program (1905).
      Its rise also occurred during a period of great scientific change which
      necessarily had influence on its trends and applications. Certainly, the French
      Republic wanted to exploit its new territory. Consequently, the colonial
      government in Hanoi would concentrate on infant morbidity and mortality.
      Nevertheless, within a few years and especially between the two world wars, the
      administrators would even provide social welfare, particularly to babies and
      grown children. Maternal and child care were priorities for the Vietnamese
      territories. However the colonial health system took local pathological,
      sociocultural, and economic contexts and peninsular medical traditions into
      account. The system was based everywhere on maternity wards and indigenous
      midwives to achieve colonial goals about fighting mortality and educating
      populations in hygiene. The data indicates that France's moves towards offering
      health care to Indochinese people improved morbidity and rates and accelerated
      medical acculturation.

PMID- 11954619
TI  - TRICARE; Civilian Health and Medical Program of the Uniformed Services (CHAMPUS);
      bonus payments in medically underserved areas. Final rule.
AB  - This final rule implements a bonus payment, in addition to the amount normally
      paid under the allowable charge methodology, to physicians in medically
      underserved areas. For purposes of this rule, medically underserved areas are the
      same as those determined by the Secretary of Health and Human Services for the
      Medicare program. Such bonus payments shall be equal to the bonus payments
      authorized by Medicare, except as necessary to recognize any unique or distinct
      characteristics or requirements of the TRICARE program, and as described in
      instructions issued by the Executive Director, TRICARE Management Activity. This
      rule promotes a reimbursement enhancement to a limited number of physicians
      designed to increase TRICARE beneficiary access to care.

PMID- 11954620
TI  - Egg donor solicitation: problems exist, but do abuses?

PMID- 11954621
TI  - Can we broker eggs without making omelets?

PMID- 11954622
TI  - Donation, disclosure, and deception.

PMID- 11954623
TI  - Exploring ovum donors' motivations and needs.

PMID- 11954624
TI  - Risky business: evaluating oocyte donation.

PMID- 11954625
TI  - Regulating the fiction of informed consent in ART medicine.

PMID- 11954626
TI  - The interests of egg donors: who is deceiving whom?

PMID- 11954627
TI  - Physician obligation in oocyte procurement.

PMID- 11954628
TI  - How should IVF programs handle initial disclosure of information to prospective
      ovum donors?

PMID- 11954629
TI  - Putting risk in perspective.

PMID- 11954630
TI  - Eggs for sale: how much is too much?

PMID- 11954631
TI  - Risk evaluation and informed consent for ovum donation: a clinical perspective.

PMID- 11954632
TI  - No news here.

PMID- 11954633
TI  - Risk information provided to prospective oocyte donors in a preliminary phone
      call.
AB  - In order to accommodate for the present shortage of oocyte donors, oocyte
      donation programs place ads in college newspapers and provide large monetary
      compensation to encourage participation. Large compensation acts as a strong
      incentive for young women to undergo the potentially risky procedure of donation.
      In this enticing situation, it is particularly important for programs to fully
      inform prospective donors of the risks of the procedure so that they can
      accurately weigh the costs and benefits of donating. However, because oocyte
      donor programs must alleviate the shortage of donors if they wish to maintain a
      financially viable business, there is reason to fear that they may minimize or
      misrepresent risks when recruiting egg donors. In this pilot study, the risk
      information provided by programs (n=19) to prospective oocyte donors in a
      preliminary phone call inquiry was investigated. The majority of the programs
      provided incomplete and/or inaccurate risk information. Policy changes are
      recommended to reduce the potential for undue influence and to standardize and
      regulate the risk information provided to prospective egg donors.

PMID- 11954635
TI  - The question of method in ethics consultation: transforming a career into a
      profession?

PMID- 11954634
TI  - The question of method in ethics consultation.
AB  - This paper offers an exposition of what the question of method in ethics
      consultation involves under two conditions: when ethics consultation is regarded
      as a practice and when the question of method is treated systematically. It
      discusses the concept of the practice and the importance of rules in constituting
      the actions, cognition, and perceptions of practitioners. The main body of the
      paper focuses on three elements of the question of method: canon, discipline, and
      history, which are treated heuristically to outline what the question of method
      in ethics consultation fully involves.

PMID- 11954636
TI  - Ethics consultation: permission from patients and other problems of method.

PMID- 11954637
TI  - Methods of conflict resolution at the bedside.

PMID- 11954638
TI  - Ethics consultation rules: a comment on George J. Agich.

PMID- 11954639
TI  - Questions of method: one ethics consultant's approach.

PMID- 11954640
TI  - Uncovering cultural bias in ethics consultation.

PMID- 11954641
TI  - The question of method in ethics consultation: the IRB frontier.

PMID- 11954642
TI  - Activities, not rules: the need for responsive practice (on the way toward
      responsibility).

PMID- 11954643
TI  - Doing ethics consultation.

PMID- 11954644
TI  - The history of medical ethics is crucial for a critical perspective in the
      continuing development of ethics consultation.

PMID- 11954645
TI  - The anatomy of bioethical consultations.

PMID- 11954646
TI  - Thinking about clinical ethics.

PMID- 11954647
TI  - A national study of ethics committees.
AB  - Conceived as a solution to clinical dilemmas, and now required by organizations
      for hospital accreditation, ethics committees have been subject only to small
      scale studies. The wide use of ethics committees and the diverse roles they have
      played compel study. In 1999 the University of Pennsylvania Ethics Committee
      Research Group (ECRG) completed the first national survey of the presence,
      composition, and activities of U.S. healthcare ethics committees (HECs). Ethics
      committees are relatively young, on average seven years in operation. Eighty-six
      percent of ethics committees report that they played a role in ongoing clinical
      decision making through clinical ethics consultation. All are engaged in
      developing institutional clinical policy. Although 4.5% of HECs write policy on
      managed care, 50% of HEC chairs feel inadequately prepared to address managed
      care. The power and activity of ethics committees parallels the composition of
      those committees and the relationship of members to their institutions. The role
      of ethics committees across the nation in making policies about clinical care is
      greater than was known, and ethics committees will likely continue to play an
      important role in the debate and resolution of clinical cases and clinical
      policies.

PMID- 11954648
TI  - Evaluation of indoor exposition to benzene, toluene, ethylbenzene, xylene, and
      styrene by passive sampling with a solid-phase microextraction device.
AB  - A solid-phase microextraction (SPME) sampling method is developed to evaluate
      indoor exposure to benzene, toluene, ethylbenzene, xylene, and styrene with gas
      chromatography and flame ionization detection for quantitative analysis. An SPME
      holder with a 100-pm polydimethylsiloxane (PDMS) and 65-pm PDMS-divinylbenzene
      fiber coating is tested in different air relative humidity conditions. The method
      gives good resolution, shows a linear response, is repeatable, and presents high
      sensitivity. This method is compared with National Institute of Occupational
      Safety and Health (NIOSH) active sampling.

PMID- 11954649
TI  - Semiquantitative determination of short-chain fatty acids in cane and beet
      sugars.
AB  - Some sugars, specifically white beet sugar and raw cane sugars, possess off
      flavors and off-odors. Although not necessarily the source, the presence of short
      chain fatty acids serves as an indicator of an off-odor problem in sugar. Solid
      phase microextraction (SPME) is used to collect the volatile compounds from the
      headspace of sugar. The temperature, moisture, and type of SPME fiber are varied
      to optimize recovery. Sugars analyzed in the absence of water using an incubation
      temperature of 70 degrees C with a divinylbenzene-carboxen-polydimethylsiloxane
      fiber yield the most reproducible results. Data from depletion analyses report a
      recovery level of 38% for the first injection. The semiquantitative analysis of
      butyric acid is accomplished using injected standards to develop a calibration
      curve.

PMID- 11954650
TI  - Semiquantitative determination of off-notes in mint oils by solid-phase
      microextraction.
AB  - Mint essential oils are produced by the steam distillation of dried or partially
      dried harvested plant material. In the United States, harvesting is done
      mechanically so that any weeds found in the field are concomitantly harvested.
      Steam distillation of contaminated plant material leads to off-notes in the oil,
      which are currently determined by a sensory panel. Furthermore, nonoptimized
      distillation conditions can lead to the thermal degradation of carbohydrates and
      proteins resulting also in the formation of very volatile off top-notes. As a
      result, the use of a nonequilibrated solid-phase microextraction (SPME) procedure
      to determine the off-notes is evaluated. The results of this evaluation include a
      combination of semiquantitative data, odor threshold data, and mathematical data
      manipulation to ascertain the capabilities of a SPME approach. The results are
      correlated with sensory panel data to yield a relatively rapid analytical
      methodology that can be used either in place of or in support of sensory
      analyses. The main advantage of the technique described is to provide some
      semiquantitative data in support of the odor-panel screening of mint oils for off
      notes. Based on the data presented in this report, it is believed that this has
      been successfully demonstrated.

PMID- 11954651
TI  - Automation of solid-phase microextraction-gas chromatography-mass spectrometry
      extraction of eucalyptus volatiles.
AB  - Solid-phase microextraction (SPME) coupled with gas chromatography (GC)-ion-trap
      mass spectrometry (ITMS) is employed to analyze fragrance compounds from
      different species of eucalyptus trees: Eucalyptus dunnii, Eucalyptus saligna,
      Eucalyptus grandis, and hybrids of other species. The analyses are performed
      using an automated system for preincubation, extraction, injection, and analysis
      of samples. The autosampler used is a CombiPAL and has much flexibility for the
      development of SPME methods and accommodates a variety of vial sizes. For
      automated fragrance analysis the 10- and 20-mL vials are the most appropriate.
      The chromatographic separation and identification of the analytes are performed
      with a Varian Saturn 4D GC-ITMS using an HP-5MS capillary column. Several
      compounds of eucalyptus volatiles are identified, with good reproducibility for
      both the peak areas and retention times. Equilibrium extraction provides maximal
      sensitivity but requires additional consideration for the effect of carryover.
      Preequilibrium extraction allows good sensitivity with minimal carryover.

PMID- 11954652
TI  - Identification of odor signature chemicals in cocaine using solid-phase
      microextraction-gas chromatography and detector-dog response to isolated
      compounds spiked on U.S. paper currency.
AB  - Solid-phase microextraction (SPME) combined with gas chromatography (GC) is
      optimized and applied to the analysis of street-cocaine samples followed by the
      field-testing of isolated chemicals using certified detector dogs. SPME proves to
      be a very sensitive and rapid method for isolating odor chemicals from street
      cocaine samples. SPME-GC and activated charcoal strip (ACS)-SPME-GC signature
      profile methods are developed for the detection and quantitation of cocaine-odor
      chemicals, including the optimization of controllable variables such as fiber
      chemistry, extraction time, and desorption time. The volatile odor chemicals in
      representative illicit cocaine samples are identified and quantitated by the ACS
      SPME-GC signature profile method and direct injection. Field tests with drug
      detector dogs show methyl benzoate to be the dominant signature odor chemical
      along with cocaine on U.S. currency at a threshold level of approximately 1-10
      microg when spiked or when 10 ng/s methyl benzoate is diffused from polymer
      bottles, which is required in order to initiate an alert. No other substance
      studied initiated consistent responses by the drug dogs. The results indicate
      that the microgram levels of cocaine that have been reported on circulated U.S.
      currency are insufficient to signal an alert from law-enforcement trained drug
      detector dogs.

PMID- 11954653
TI  - Separation and identification of the phthalic anhydride derivatives of Liqusticum
      Chuanxiong Hort by GC-MS, TLC, HPLC-DAD, and HPLC-MS.
AB  - A simple, sensitive, and rapid method using gas chromatography (GC)-mass
      spectrometry (MS) is developed for the simultaneous separation and identification
      of the active ingredients of Liqusticum Chuanxiong Hort (Chuanxiong). Ten
      phthalic anhydride derivatives (PADs) are identified in Chuanxiong as 3
      butylphthalide, 3-butylidenephthalide, 3-butylidene-4-hydroxyphthalide,
      senkyunolide A, neocnidilide, Z-ligustilide, E-ligustilide, senkyunolide F,
      senkyunolide-H, and senkyunolide-I. The existence of ferulic acid and vanillin in
      Chuanxiong extract is also demonstrated. Further identification of these
      compounds is performed by thin-layer chromatography, high-performance liquid
      chromatography (HPLC), and HPLC-MS analysis. This is the first report of the
      separation and determination of the PADs in Chuanxiong by GC-MS.

PMID- 11954654
TI  - Use of nonionic poly(ethylene glycol) p-isooctyl-phenyl ether (Triton X-1 00)
      surfactant mobile phases in the thin-layer chromatography of heavy-metal cations.
AB  - The analytical potential of poly(ethylene glycol) p-isooctyl-phenyl ether (Triton
      X-100), a nonionic surfactant, is used as a mobile phase in the thin-layer
      chromatographic separation of heavy-metal cations. The surfactant concentration
      below its critical micellar concentration (CMC) as well as above the CMC value is
      used to investigate the migrational behavior of some heavy-metal ions on silica
      gel layers. The mobility of the metal ions is found to change marginally with the
      increase of surfactant concentration from 0.001M (below CMC) to 0.1M (above CMC).
      The influence of the pH of the medium, nonelectrolyte organic (urea and
      alkanols), and inorganic electrolyte (NaCI) additives in the surfactant
      containing mobile phase on the mobility of heavy metals on the silica gel layer
      is examined. For separating metal ions, surfactant must be used in the presence
      of buffers. Triton X-100 (0.02M) at pH 2.3 is found to be the best mobile phase
      for the separation of heavy-metal cations. In general, the presence of alcohol in
      aqueous surfactant solutions results in a decrease in the mobility of metal ions.
      Besides Cu2+ and Fe3+, all of the metal ions show a trend of increasing the
      retardation factor beyond a minima at 0.1 or 0.3M of added urea or NaCl. The
      proposed method is successfully applied for the simultaneous detection of Zn2+
      and Cd2+ from a spiked human blood sample.

PMID- 11954655
TI  - HPLC and LC-MS studies of the transesterification reaction of methylparaben with
      twelve 3- to 6-carbon sugar alcohols and propylene glycol and the isomerization
      of the reaction products by acyl migration.
AB  - Sugar alcohols and parabens are commonly used ingredients in oral suspension
      formulations. However, their possible incompatibility because of
      transesterification reaction is a concern during formulation development. In
      order to gain more knowledge about the reaction, a high-performance liquid
      chromatographic (HPLC) method is developed to separate the transesterification
      reaction products of methylparaben preservative with twelve 3- to 6-carbon sugar
      alcohols and propylene glycol. It is found that the number of peaks separated or
      partially separated correlate well with the number of distinct hydroxyl groups
      present in the sugar alcohol molecules. This means that all the hydroxyl groups
      in a sugar alcohol molecule can react with methylparaben to form
      transesterification reaction products. These products are positional isomers that
      have identical UV spectra with a maximum at 255 nm and the same m/z ratio for
      molecular ions by liquid chromatography-mass spectrometry. When isolated
      individually, they can isomerize (interconvert) under suitable conditions to form
      other positional isomers by intramolecular acyl migration. The acyl migration
      pathway for each of the isolated positional isomers from the transesterification
      reaction of methylparaben with sorbitol, ribitol, and xylitol is followed by
      HPLC. Based on the information, a tentative assignment of the six isomer peaks
      generated from the transesterification reaction between methylparaben and
      sorbitol is proposed.

PMID- 11954656
TI  - Rules for changing flow rates in HPLC silica-based columns.

PMID- 11954657
TI  - Why are there retention time drifts in my GC oven?

PMID- 11954659
TI  - Detection of glycated gastric inhibitory polypeptide within the intestines of
      diabetic obese (ob/ob) mice.
AB  - Gastric inhibitory polypeptide (GIP) is produced within endocrine cells of the
      small intestine and released into the circulation upon nutrient ingestion. This
      study has quantified the levels of this insulinotropic peptide in the intestines
      of lean and diabetic obese ob/ob mice and estimated the proportion that is
      glycated. The total intestinal GIP concentration and content of the diabetic mice
      were significantly greater (p < 0.01) than that of control animals. Affinity
      chromatographic separation and side-viewing GIP radioimmunoassay demonstrated
      that approx 20% of the GIP extracted from intestines of ob/ob mice was present in
      glycated form. Less than 2% of intestinal GIP was glycated in lean mice. In
      conclusion substantial quantities of glycated GIP exist within the intestines of
      diabetic ob/ob mice, suggesting that this may be a contributing factor to the
      physiological disarray of this syndrome.

PMID- 11954658
TI  - Recent discoveries in physiology of insulin-like growth factor-1 and its
      interaction with gonadotropins in folliculogenesis.
AB  - Ovarian follicular development is under the influence of gonadotrophins. The
      manner by which gonadotrophins achieve their role in cell replication and hormone
      production is through other specialized molecules. Insulin-like growth factor-1
      (IGF-1) is considered to be one of the most important of these molecules. IGF-1
      is present in relatively large amounts in the ovary and the IGF-1 gene is
      expressed in the graafian follicle. IGF-1 binding proteins modulate the action of
      IGF-1 and are influenced by gonadotrophins. Null mutations of genes encoding IGF
      1 and type-1 IGF receptor have demonstrated the obligatory role of IGF-1 in
      folliculogenesis. It was proposed that IGF-1 may be an obligatory mediator of
      gonadotrophin-induced folliculogenesis and that the interaction is synergistic.
      From this point, one group embarked on a series of physiological studies to
      further elucidate the interaction of these molecules. We discovered that,
      according to circumstances, follicle stimulating hormone (FSH) may act with IGF-1
      synergistically (as was postulated before), additively, independently, or even
      antagonistically. We discovered that granulosa cells must first be exposed to FSH
      and then they respond well to IGF-1. All previous studies of granulosa cells were
      done on mural granulosa cells. We subsequently showed that cumulus type of
      granulosa cells (adjacent to the oocyte) behave differently in their responses to
      gonadotrophins and IGF-1.

PMID- 11954660
TI  - Biochemical evidence of the functional recovery and regeneration of adrenal
      autotransplants in the rat spleen.
AB  - Adrenal transplantation may restore adrenal function after bilateral
      adrenalectomy or when adrenal function is lost. Thus, animal experiments could
      provide useful information before clinical application of adrenal
      transplantation. Using an experimental model of autotransplantion of a complete
      adrenal gland in the spleen of adrenalectomized rats, several biochemical and
      hormonal parameters were studied to evaluate the function of transplanted adrenal
      tissue compared to control and adrenalectomized animals. Three weeks after
      surgery, the animals were sacrificed and plasma and tissue samples were obtained
      for biochemical studies. In the autotransplanted rats, plasma glucose, hepatic
      glycogen, plasma, and hepatic proteins, which were decreased in adrenalectomized
      rats, increased to values close to those of the control group; whereas muscle and
      thymus proteins, which were increased in adrenalectomized animals, decreased and
      reached normal levels. Corticosterone plasma levels in autotransplanted rats
      showed a 50% recovery compared to control animals, whereas plasma aldosterone
      concentrations were low, with similar values to those of the adrenalectomized
      group. These results provide evidence that the adrenal grafts secrete
      corticosterone in quantities enough to overcome hepatic inactivation. On the
      other hand, aldosterone plasma concentrations remain very low, plasma potassium
      levels are increased, and plasma sodium levels are decreased in animals with
      intrasplenic adrenal grafts, indicating that aldosterone production is
      insufficient to avoid hypoaldosteronism.

PMID- 11954661
TI  - Decreased expression of fos-related antigens (FRAs) in the hypothalamic
      dopaminergic neurons after immunoneutralization of endogenous prolactin.
AB  - In our previous studies we found that administration of exogenous prolactin
      increased dopamine turnover in the terminal areas of the hypothalamic
      dopaminergic neurons controlling prolactin secretion from pituitary lactotrophs.
      In this study we investigated the effect of immunoneutralization of endogenous
      prolactin on the expression of FRAs in the tuberoinfundibular dopaminergic
      (TIDA), tuberohypophysial dopaminergic (THDA), and periventricular hypothalamic
      dopaminergic (PHDA) subpopulations of the hypothalamic dopaminergic neurons.
      Female rats were ovariectomized on d 0 of the experiment. At 1000 h of d 10, all
      animals were injected with 20 microg of 17-beta-estradiol sc to induce a
      proestrous-like surge of prolactin at 1700 h the next day. At 1000 h on d 11,
      half of the animals were injected with 200 microL of rabbit anti-rat prolactin
      antiserum ip, while the controls received normal rabbit serum. Groups of animals
      were sacrificed for immunocytochemistry in 2 h intervals between 1300 and 2100 h.
      Double-label immunocytochemistry for FRAs and tyrosine hydroxylase (TH) was
      performed and the results are presented as percentage of TH-immunoreactive
      neurons expressing FRAs. In the control animals, expression of FRAs decreased at
      1500 h, gradually increased by 1900 h, but was lower than the basal levels by
      2100 h. Expression of FRAs was significantly lower at 1900 h in the PHDA, THDA
      and TIDA neurons of prolactin antiserum treated rats than in the controls. These
      results indicate that elimination of endogenous prolactin from the circulation
      lowers the activity and/or prevents the reactivation of neuroendocrine
      dopaminergic neurons at the beginning of the dark phase.

PMID- 11954662
TI  - Selective suppression of renal Na+/H+ exchanger isoform-3 by prolonged
      stimulation of rats with adrenocorticotropic hormone.
AB  - Prolonged stimulation with adrenocorticotropic hormone (ACTH) causes hypertension
      and increases Na+ intake and urine output in humans and animals. However, its
      biochemical basis remains to be established. Since renal Na+/H+ exchanger
      isoforms (NHE) and the sodium pump play an important role in this condition,
      their levels were examined in rats stimulated with ACTH. Male Wistar rats
      received daily sc injection of ACTH (30 microg/100 g of body wt) for 4 d. Half of
      the ACTH-stressed rats were kept for four additional days without injection of
      ACTH (poststimulation). In a third group, the animals were treated with
      dexamethasone (50 microg/100 g of body wt) daily for 4 d. A fourth group
      consisted of unstressed control animals. Levels of NHE proteins were measured by
      Western blot analysis. Sodium pump activity was assessed by the level of ouabain
      sensitive K-stimulated p-nitrophenylphosphatase activity (PNP) in the renal
      cortex. ACTH caused a selective decrease in NHE-3, but not of NHE-1 or alpha
      actin levels. Interestingly, this ACTH-induced change was not duplicated in the
      animals treated with dexamethasone. Immunofluorescence data demonstrated that NHE
      3 is located in the renal proximal tubules. PNP activity, on the contrary, was
      increased in both the ACTH-stimulated and dexamethasone-treated animals. More
      important, these changes in NHE-3 and PNP activity returned to the control level
      poststimulation. In conclusion, while PNP upregulation may be mediated by
      adrenocortical glucocorticoid, a role for glucocorticoids in the suppression of
      NHE-3 is less clear. These changes might impair renal tubular Na+ reabsorption
      and hence increase Na+ and water excretion in ACTH stimulation, thus acting as a
      counterbalance to normalize blood pressure in ACTH-stimulated animals.

PMID- 11954663
TI  - Daily low-dose administration of growth hormone secretagogue stimulates pulsatile
      growth hormone secretion and elevates plasma insulin-like growth factor-1 levels
      in pigs.
AB  - Repeated administration of growth hormone secretagogues (GHSs) has proven to be a
      delicate matter owing to development of tolerance. The aim of the present study
      was to define conditions during which the responsiveness to the orally active
      NN703 was maintained over several days. Growing pigs were fitted with stomach and
      vascular catheters, permitting unstressed intragastric administrations and blood
      sampling. NN703 or vehicle was administered once daily. When NN703 was given at a
      dose of 18 mg/kg, there was a massive acute increase in plasma growth hormone
      (GH) levels, but this was only seen on the first day of administration. A dose of
      1.8 mg/kg did not cause a significant acute increase in plasma GH concentrations,
      whereas stimulation of pulsatile GH release was sustained over a 4-d period.
      During the first 7 h following injection of vehicle, the area under the curve of
      plasma GH was 1211+/-144 (microg/[L x 7 h]), but increased to 1770+/-269 and
      1824+/-198 (microg/[L x 7 h]) on the first and fourth day of NN703
      administration, respectively. Deconvolution analysis of the 7-h profiles revealed
      that the GH mass per burst as well as the GH burst amplitude were significantly
      (p < 0.001) increased during treatment with NN703, which led to an increase in
      pulsatile GH secretion rate (p < 0.001). Insulin-like growth factor-1 plasma
      concentrations increased steadily during NN703 administration (p < 0.01) and
      decreased after termination of treatment. The sustained increase in GH
      pulsatility observed with low-dose NN703 treatment suggests that development of
      tolerance to this GHS may be obviated by minimization of dose.

PMID- 11954664
TI  - Central administration of neuromedin U activates neurons in ventrobasal
      hypothalamus and brainstem.
AB  - Neuromedin U (NMU) is a peptide isolated from the porcine spinal cord. Recently,
      two receptors for NMU have been identified and characterized. A recent study
      indicated that NMU is an anorectic chemical in the brain. The present study shows
      that NMU has an action in the brain to inhibit food intake in rats.
      Intracerebroventricular injection of NMU inhibited dark-phase feeding. Animals
      injected with NMU showed a strong increase in Fos-immunoreactive nuclei in the
      paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus,
      and in the parabrachial nucleus of the brain stem. Double immunohistochemistry
      revealed that a high number of oxytocin-immunoreactive neurons in the PVN and SON
      contained Fos after intracerebroventricular injection of NMU. In addition, a
      small proportion of vasopressinergic cells within the PVN and SON were found to
      contain Fos. The effect of NMU on the hypothalamus and brain stem contributes to
      the inhibitory effects of NMU on feeding behavior.

PMID- 11954665
TI  - Tissue kallikrein and bradykinin B2 receptor in human uterus in luteal phase and
      in early and late gestation.
AB  - This study was addressed to evaluate the temporospatial pattern of key components
      of the kallikreinkinin system in human uterus in luteal phase (n = 7), early
      pregnancy (isolated spontaneous abortions, n = 11; ectopic pregnancies, n = 9),
      idiopathic preterm deliveries (n = 5), and term gestations (n = 12). Tissue
      kallikrein mRNA and protein and the type 2 bradykinin receptor (B2R) protein were
      expressed in luminal and glandular epithelium and in endothelial cells of stromal
      and myometrial blood vessels, while tissue kallikrein mRNA and B2R, but not
      tissue kallikrein protein, were observed in decidual cells and in arteriolar and
      myometrial muscle. A greater signal intensity for tissue kallikrein mRNA and
      protein and of B2R protein was observed in the early pregnancy samples. The sites
      and variations of the tissue kallikrein mRNA and protein and of the B2R protein
      in the human uterus and in fallopian tubes during the luteal phase and in
      pregnancy coincide with those described for other vasoactive effectors such as
      nitric oxide, prostacyclins, growth factors, and renin. The uterine localization
      of the main enzyme and receptor of the tissue kallikrein-kinin system in key
      sites for embryo attachment, implantation, placentation, maintenance of placental
      blood flow, and parturition supports the notion that the kallikreinkinin system
      participates in these processes, probably through vasodilation, increased
      vasopermeability, enhanced matrix degradation, stimulation of cell proliferation,
      and myometrial contractility.

PMID- 11954666
TI  - Transactivation of progestin- and estrogen-responsive promoters by 19-nor
      progestins in African Green Monkey Kidney CV1 cells.
AB  - New and more potent progestins and antiprogestins suitable for reproductive
      therapy and contraception are currently the target of intensive research. The
      design of such drugs has been hampered by the complex technology required for
      screening these compounds at the molecular level. To solve this problem, we
      developed an in vitro cell system that allows detection of the progestagenic
      effects of a given compound using a PRE2-TATA-CAT reporter vector transiently
      introduced in a cell line stably transfected with the rabbit progesterone
      receptor (PR). The African Green Monkey Kidney CV1 (AGMK-CV1) cell line was
      chosen because these cells do not express endogenous steroid receptors; the
      selected clone stably expressing the rabbit PR has been maintained in our
      laboratory for more than 2 yr without detectable losses in PR content and
      progestagenic response. The presence and function of the PR were assessed by
      immunohistochemical and saturation analyses as well as by monitoring
      transactivation of the PRE2-TATA-CAT reporter gene. In this cell line, the PR is
      expressed at a concentration of 0.170 fmol/mg of protein, and the receptor is
      localized within the cell nucleus in either the presence or absence of the potent
      synthetic progestin R5020. This PR-expressing cell system allowed study of the in
      vitro progestational activity of several 19-nor progestins. The antiprogestin
      RU486 inhibited CAT activity induced by R5020; norethisterone (NET),
      levonorgestrel (LNG), and gestodene (GSD) induced PRE2-TATA-CAT activity at
      concentrations similar to those of R5020, whereas NET A-ring-reduced metabolites
      induced CAT activity at an extent lower than (5alpha-NET) or similar
      (3beta,5alpha-NET) to that of the precursor compound. The PRE2-TATA-CAT induction
      by 17beta-estradiol was also analyzed and no crossreactivity was detected.
      However, when the ERE-VitA2-TK-CAT (estrogen-responsive element-vitellogenin A2
      thymidine kinase promoter-CAT) reporter vector and the estradiol receptor alpha
      or beta were cotransfected, CAT activity was induced in the presence of 17beta
      estradiol, and NET tetrahydro-reduced derivatives. The results indicate that this
      AGMK-CV1-PR cell assay system appears to be suitable for measuring the effects of
      different synthetic progestins at the transcriptional level. In this assay
      system, NET, LNG, and GSD exhibit potent progestational effects at the
      transcriptional level. In the particular case of NET, the assay system allowed us
      to determine that the single or multiple hormonal transcriptional effects of this
      compound are partially mediated by its A-ring-reduced derivatives.

PMID- 11954668
TI  - Awareness of ageism, motivation, and countertransference in the care of elders
      with Alzheimer's disease.
AB  - This article focuses on the importance of a practitioner's awareness of ageism,
      motivation, and countertransference in working with elders with dementia. These
      factors have the capacity to significantly affect a professional's performance.
      Additionally, they may also affect the type and quality of services a memory
      impaired client receives. Ageism is discussed at the micro, mezzo, and macro
      level, and practitioners are urged to develop an increased awareness of the
      effects of ageism on client/service options and as well as practitioner's
      beliefs. Monitoring professional motivation and being aware of
      countertransference are important considerations in practitioner-client
      relationships. Professionals are encouraged to incorporate personal introspection
      and consultation or supervision to ensure that clients receive the most
      appropriate service available. Case examples are provided to illustrate concepts.

PMID- 11954669
TI  - Caregiving appraisal and interventions based on the progressively lowered stress
      threshold model.
AB  - The purpose of this article is to describe the impact of a theoretically driven,
      psychoeducational intervention based on the Progressively Lowered Stress
      Threshold (PLST) model on caregiving appraisal among community-based caregivers
      of persons with Alzheimer's disease and related disorders. A total of 241
      subjects completed the year-long study in four sites in Iowa, Minnesota, Indiana,
      and Arizona. Caregiving appraisal was measured using the four factors of the
      Philadelphia Geriatric Center Caregiving Appraisal Scale: mastery, burden,
      satisfaction, and impact. Analysis of trends over time showed that the
      intervention positively affected impact, burden, and satisfaction but had no
      effect on mastery when measured against the comparison group. The PLST model was
      influential in increasing positive appraisal and decreasing negative appraisal of
      the caregiving situation.

PMID- 11954667
TI  - Effects of age on elements of insulin-signaling pathway in central nervous system
      of rats.
AB  - Insulin resistance is known to play a pivotal role in type 2 diabetes. Senile
      individuals, besides being prone to insulin resistance and, consequently, to type
      2 diabetes, manifest diseases of the central nervous system (CNS) that may be
      influenced by disturbances of insulin signaling in the brain, such as memory
      impairment, Parkinson disease, and Alzheimer disease. We investigated the
      expression and response to insulin of elements involved in the insulin-signaling
      pathway in the forebrain cortex and cerebellum of rats ages 1 d to 60 wk. The
      protein content of insulin receptors and SRC homology adaptor protein (SHC) did
      not change significantly along the time frame analyzed. However, insulin-induced
      tyrosine phosphorylation of the insulin receptor and SHC, and the association of
      SHC/growth factor receptor binding protein-2 (GRB2) decreased significantly from
      d 1 to wk 60 of life in both types of tissues. Moreover, the expression of SH
      protein tyrosine phosphatase-2 (SHP2), a tyrosine phosphatase involved in insulin
      signal transduction and regulation of the insulin signal, decreased significantly
      with age progression, in both the forebrain cortex and the cerebellum of rats.
      Thus, elements involved in the insulin-signaling pathway are regulated at the
      expression and/or functional level in the CNS, and this regulation may play a
      role in insulin resistance in the brain.

PMID- 11954670
TI  - AD-venture program: therapeutic biking for the treatment of depression in long
      term care residents with dementia.
AB  - This project tested an innovative intervention in a controlled clinical
      investigation of a nonpharmacological treatment of depression in long-term care
      residents with dementia. This treatment utilized a wheelchair bicycle in a
      recreation therapy protocol, which combined small group activity therapy and one
      to-one bike rides with a staff member. Depression levels were significantly
      reduced in the two-week portion of the study with levels maintained in the 10
      week maintenance period. Improvements were also found in sleep and levels of
      activity engagement.

PMID- 11954671
TI  - Caregiving is an age-normative event.

PMID- 11954672
TI  - Co-morbidity associated with dementia.
AB  - PURPOSE: The purpose of this study was to identify common co-morbid conditions
      associated with dementia subtypes and to evaluate the association of
      hypertension, diabetes mellitus, atrial fibrillation, congestive heart failure,
      and anemia with dementia subtypes relative to controls. METHODS: Hospital
      discharge data were used to identify 15,013 subjects from South Carolina with a
      diagnosis of dementia between 1998 and 1999. A control group of 15,013 persons
      without dementia was randomly sampled from hospital discharge records and matched
      to persons with dementia on the basis of age, race, and gender. Multiple
      hospitalizations for each patient were merged, and repeated diagnoses during
      separate hospitalizations were counted once. RESULTS: After adjusting for age,
      race, and gender, persons with Alzheimer's disease and dementia associated with
      medical conditions were less likely to be diagnosed with hypertension, diabetes,
      congestive heart failure, and atrial fibrillation than were controls. Patients
      with multi-infarct dementia were also less likely to have congestive heart
      failure, but were more likely to have diabetes. Anemia was not associated with
      any dementia subtype. CONCLUSIONS: There are distinct differences in comorbid
      conditions among dementia subtypes. Our research does not support previous
      studies that suggest a circulatory component to the development of Alzheimer's
      disease.

PMID- 11954673
TI  - The JNK/c-Jun cascade and Alzheimer's disease.
AB  - Emerging evidence indicates that the JNK/c-Jun cascade is activated in neurons of
      the Alzheimer's disease brain and suggests its involvement in abnormal processes,
      ranging from tau phosphorylation to neuronal death. Substantial new data have
      accumulated on the functional relevance of causative genes in familial
      Alzheimer's disease and the pathological processes that occur within neurons. In
      this review, we summarize reported findings of the JNK/c-Jun cascade in
      Alzheimer's disease and discuss the relationship between the cascade and other
      pathological processes. We suggest that the effort to connect amyloid deposition
      with intracellular activation of the JNK/c-Jun cascade may modify the amyloid
      theory of Alzheimer's disease. Therapeutic approaches targeting the JNK/c-Jun
      cascade and other signaling may complement therapeutic strategies directed at
      reducing amyloid deposition.

PMID- 11954674
TI  - Multimodal behavior management for people with dementia.
AB  - Various psychological approaches are effective in maintaining and maximizing
      functioning in Alzheimer's disease. The most efficacious approaches have been
      based on a combination of individualized, interdisciplinary, and holistic
      treatment. Such a treatment approach is comparable to Lazarus's multimodal model,
      which has also been referred to as "systematic eclecticism." The multimodal model
      is especially well suited for people experiencing dementia, a progressive
      disorder

PMID- 11954675
TI  - Use of a false recognition paradigm in an Alzheimer's disease clinical trial: a
      pilot study.
AB  - We report the first use of a false recognition memory test in a clinical trial of
      patients with Alzheimer's disease (AD). Tests of false recognition allow
      measurement of two components of memory: the specific details of a prior
      encounter with a particular item (item-specific recollection) and the general
      meaning, idea, or gist conveyed by a collection of items (gist memory). We used a
      false recognition paradigm with categorized pictures to study the effects of an
      experimental medication in patients with AD. Because medications to treat AD may
      preferentially improve gist memory or item-specific recollection, use of this
      type of paradigm may improve sensitivity for detection of drug effects more than
      standard memory tests.

PMID- 11954676
TI  - Pathogenomic mechanisms for particulate matter induction of acute lung injury and
      inflammation in mice.
AB  - To begin identifying genes controlling individual susceptibility to particulate
      matter, responses of inbred mouse strains exposed to nickel sulfate (NiSO4*) were
      compared with those of mice exposed to ozone (O3) or polytetrafluoroethylene
      (PTFE). The A strain was sensitive to NiSO4-induced lung injury (quantified by
      survival time), the C3H/He (C3) strain and several other strains were
      intermediate in their responses, and the C57BL/6 (B6) strain was resistant. The
      strains showed a pattern of response similar to the patterns of response to O3
      and PTFE. The phenotype of A x B6 offspring (B6AF1) resembled that of the
      resistant B6 parental strain, with strains exhibiting sensitivity in the order A
      > C3 > B6 = B6AF1. Pathology was comparable for the A and B6 mice, and exposure
      to NiSO4 at 15 microg/m3 produced 20% mortality in A mice. Strain sensitivity for
      the presence of protein or neutrophils in lavage fluid differed from strain
      sensitivity for survival time, suggesting that they are not causally linked but
      are controlled by an independent gene or genes. In the B6 strain, exposure to
      nickel oxide (NiO) by instillation (40 to 1000 nm) or inhalation (50 nm) produced
      no changes, whereas inhalation of NiSO4 (60 or 250 nm) increased lavage proteins
      and neutrophils. Complementary DNA (cDNA) microarray analysis with 8,734 sequence
      verified clones revealed a temporal pattern of increased oxidative stress,
      extracellular matrix repair, cell proliferation, and hypoxia, followed by a
      decrease in surfactant-associated proteins (SPs). Certain expressed sequence tags
      (ESTs), clustered with known genes, suggest possible coregulation and novel roles
      in pulmonary injury. Finally, locus number estimation (Wright equation) and a
      genomewide analysis suggested 5 genes could explain the survival time and
      identified significant linkage for a quantitative trait locus (QTL) on chromosome
      6, Aliq4 (acute lung injury QTL4). Haplotype analysis identified an allelic
      combination of 5 QTLs that could explain the difference in sensitivity to acute
      lung injury between parental strains. Positional candidate genes for Aliq4
      include aquaporin-1 (Aqp1), SP-B, and transforming growth factor-alpha (TGF
      alpha). Transgenic mice expressing TGF-alpha were rescued from NiSO4 injury (that
      is, they had diminished SP-B loss and increased survival time). These findings
      suggest that NiSO4-induced acute lung injury is a complex trait controlled by at
      least 5 genes (all possibly involved in cell proliferation and surfactant
      function). Future assessment of these susceptibility genes (including evaluations
      of human synteny and function) could provide valuable insights into individual
      susceptibility to the adverse effects of particulate matter.

PMID- 11954677
TI  - Real-world particulate matter and gaseous emissions from motor vehicles in a
      highway tunnel.
AB  - Recent studies have linked atmospheric particulate matter with human health
      problems. In many urban areas, mobile sources are a major source of particulate
      matter (PM) and the dominant source of fine particles or PM2.5 (PM smaller than
      2.5 pm in aerodynamic diameter). Dynamometer studies have implicated diesel
      engines as being a significant source of ultrafine particles (< 0.1 microm),
      which may also exhibit deleterious health impacts. In addition to direct tailpipe
      emissions, mobile sources contribute to ambient particulate levels by brake and
      tire wear and by resuspension of particles from pavement. Information about
      particle emission rates, size distributions, and chemical composition from in-use
      light-duty (LD) and heavy-duty (HD) vehicles is scarce, especially under real
      world operating conditions. To characterize particulate emissions from a limited
      set of in-use vehicles, we studied on-road emissions from vehicles operating
      under hot-stabilized conditions, at relatively constant speed, in the Tuscarora
      Mountain Tunnel along the Pennsylvania Turnpike from May 18 through 23, 1999.
      There were five specific aims of the study. (1) obtain chemically speciated
      diesel profiles for the source apportionment of diesel versus other ambient
      constituents in the air and to determine the chemical species present in real
      world diesel emissions; (2) measure particle number and size distribution of
      chemically speciated particles in the atmosphere; (3) identify, by reference to
      data in years past, how much change has occurred in diesel exhaust particulate
      mass; (4) measure particulate emissions from LD gasoline vehicles to determine
      their contribution to the observed particle levels compared to diesels; and (5)
      determine changes over time in gas phase emissions by comparing our results with
      those of previous studies. Comparing the results of this study with our 1992
      results, we found that emissions of C8 to C20 hydrocarbons, carbon monoxide (CO),
      and carbon dioxide (CO2) from HD diesel emissions substantially decreased over
      the seven-year period. Particulate mass emissions showed a similar trend.
      Considering a 25-year period, we observed a continued downward trend in HD
      particulate emissions from approximately 1,100 mg/km in 1974 to 132 mg/km
      (reported as PM2.5) in this study. The LD particle emission factor was
      considerably less than the HD value, but given the large fraction of LD vehicles,
      emissions from this source cannot be ignored. Results of the current study also
      indicate that both HD and LD vehicles emit ultrafine particles and that these
      particles are preserved under real-world dilution conditions. Particle number
      distributions were dominated by ultrafine particles with count mean diameters of
      17 to 13 nm depending on fleet composition. These particles appear to be
      primarily composed of sulfur, indicative of sulfuric acid emission and
      nucleation. Comparing the 1992 and 1999 HD emission rates, we observed a 48%
      increase in the NOx/CO2 emissions ratio. This finding supports the assumption
      that many new-technology diesel engines conserve fuel but increase NOx emissions.

PMID- 11954678
TI  - Airborne carbonyls from motor vehicle emissions in two highway tunnels.
AB  - Carbonyls (aldehydes and ketones) continue to receive scientific and regulatory
      attention as toxic air contaminants, mutagens, and carcinogens. Vehicle emissions
      are a major source of carbonyls in outdoor air, but information about the nature
      and magnitude of carbonyl emissions by motor vehicles is limited. The objective
      of this study was to identify speciated carbonyls emitted by motor vehicles under
      real-world, on-road conditions and to calculate on-road carbonyl emission
      factors. We collected air samples at the inlet and outlet of two highway tunnels,
      the Caldecott Tunnel near San Francisco and the Tuscarora Mountain Tunnel in
      Pennsylvania. At the Caldecott Tunnel, the fleet consisted almost entirely of
      light-duty (LD) vehicles that used California phase 2 reformulated gasoline.
      Vehicle count, speed and other parameters relevant to carbonyl emissions were
      nearly the same from one assessment to the next. At the Tuscarora Mountain
      Tunnel, the fleet included LD vehicles and heavy-duty (HD) diesel trucks. This
      part of the study was designed to capture differences in percentage of LD and HD
      vehicles from one assessment to the next. Air downstream of KI oxidant scrubbers
      was sampled on silica gel cartridges coated with 2,4-dinitrophenylhydrazine
      (DNPH). Carbonyls were identified as their DNPH derivatives by liquid
      chromatography (LC) with detection by diode-array, UV-visible spectroscopy and by
      atmospheric pressure negative-ion chemical ionization mass spectrometry (MS).
      About 100 carbonyls were identified. For about 30 of these carbonyls,
      concentrations were measured at the inlet and outlet of both tunnels. This
      information was used to calculate on-road carbonyl emission factors for LD
      vehicles (Caldecott Tunnel) and for the overall fleet (Tuscarora Mountain
      Tunnel). At the Tuscarora Mountain Tunnel, data for the fleet were used to
      calculate carbonyl emission factors for LD vehicles and for HD diesel trucks, the
      majority of which were weight class 7-8 trucks. Carbonyl emission factors at the
      Caldecott Tunnel were calculated as milligrams of emissions per liter of fuel
      consumed. Those at the Tuscarora Mountain Tunnel were calculated as milligrams of
      emissions per distance traveled and then converted to milligrams per liter using
      the fuel economy reported by Gertler et al (2000) for this tunnel (14.75 km/L for
      LD vehicles and 3.15 km/L for HD vehicles). At the Caldecott Tunnel, the LD
      vehicles emission factor was 68.4 mg/L for total measured carbonyls; the ten most
      abundant carbonyls were, in decreasing order, formaldehyde, acetaldehyde,
      benzaldehyde, acetone, m-tolualdehyde, p-tolualdehyde, methacrolein, o
      tolualdehyde, 2,5-dimethylbenzaldehyde, and crotonaldehyde. At the Tuscarora
      Mountain Tunnel, the LD emission factor was 94.9 mg/L for total measured
      carbonyls; the ten most abundant carbonyls were formaldehyde, acetone,
      acetaldehyde, heptanal, crotonaldehyde, 2-butanone, propanal, acrolein,
      methacrolein, and benzaldehyde. The weight class HD 7-8 vehicle emission factor
      at the Tuscarora Mountain Tunnel was 82.1 mg/L for total measured carbonyls; the
      ten most abundant carbonyls were formaldehyde, acetaldehyde, acetone,
      crotonaldehyde, m-tolualdehyde, 2-pentanone, a C5 saturated aliphatic carbonyl, 2
      butanone, benzaldehyde, and methacrolein. The most abundant carbonyl was
      formaldehyde, which accounted for 45.4% (Caldecott, LD vehicles), 40.1%
      (Tuscarora Mountain, LD vehicles), and 25.8% (Tuscarora Mountain, HD vehicles) of
      total measured carbonyl emissions. The three most abundant carbonyls,
      formaldehyde, acetaldehyde, and acetone, together accounted for 63.0% (Caldecott,
      LD vehicles), 76.5% (Tuscarora Mountain, LD vehicles), and 50.5% (Tuscarora
      Mountain, HD vehicles) of total carbonyl emissions. At the Tuscarora Mountain
      Tunnel, HD vehicles emitted more unsaturated carbonyls, aromatic carbonyls, and
      dicarbonyls (as a percentage of total carbonyl emissions) than did LD vehicles.
      For LD vehicles, less acetone and more aromatic carbonyls (as a percentage of
      total carbonyl emissions) were emitted at the Caldecott Tunnel than at the
      Tuscarora Mountain Tunnel. The highway tunnel studies described in the main body
      of the report also offered an opportunity to examine the role of the sampling
      substrate, a critical aspect of the carbonyl sampling protocol. The results are
      described in Appendix A. Co-located samples, one collected using a DNPH-coated
      silica gel cartridge and the other using a DNPH-coated C18 cartridge, were
      collected downstream of KI oxidant scrubbers at the inlet and outlet of the
      Caldecott Tunnel. Statistical comparisons of the concentrations measured for
      about 30 carbonyls indicated good agreement between silica gel cartridges and C18
      cartridges for about 25 carbonyls, including formaldehyde and acetaldehyde.
      Concentrations of acetone and 2-butanone measured using C18 cartridges were lower
      than those measured using silica gel cartridges.

PMID- 11954679
TI  - Appropriateness of coronary revascularization for patients with chronic stable
      angina or following an acute myocardial infarction: multinational versus Dutch
      criteria.
AB  - OBJECTIVE: We convened a multinational panel to develop appropriateness criteria
      for percutaneous transluminal coronary angioplasty (PTCA) and coronary artery
      bypass graft (CABG). To assess the applicability of these criteria, we applied
      them to patients referred for coronary revascularization. Finally, to understand
      how multinational criteria may differ from criteria developed by a panel of
      physicians from one country, we compared the appropriateness ratings using the
      multinational panel's criteria and those made using similar criteria previously
      developed by a panel of Dutch physicians. METHODS: We conducted a prospective
      survey and review of the medical records of 2363 consecutive patients presenting
      with chronic stable angina or following a myocardial infarction who were referred
      for PTCA (n=1137) or CABG (n= 1226) at ten Dutch hospitals performing coronary
      revascularization. Appropriateness was measured using two sets of criteria
      developed by: (1) a Dutch panel of cardiologists and cardiothoracic surgeons in
      1991; and (2) a similarly composed European panel in 1998. RESULTS: More PTCA
      referrals were rated inappropriate by Dutch criteria compared with multinational
      criteria among both patients with chronic stable angina (34.8 versus 6.1%; P<
      0.001) and those with a recent myocardial infarction (28.1 versus 0.9%; P<
      0.001). Among those patients referred for bypass surgery, the Dutch criteria
      judged a greater proportion of cases inappropriate than multinational criteria
      did for patients with chronic stable angina (3.7 versus 1.5%, P< 0.001). The
      proportion of cases rated inappropriate for bypass surgery among patients
      following a myocardial infarction was similar between the two panels (3.9 versus
      2.4%, respectively; P=0.40). After reclassifying the data for two of the clinical
      factors used in the appropriateness criteria (lesion morphology and intensity of
      medical therapy) based on evidence that appeared in the literature after the
      Dutch panel met, we found no significant differences between the Dutch and
      multinational panels' appropriateness ratings. CONCLUSIONS: While fewer cases
      were judged inappropriate using the multinational criteria compared with the
      Dutch criteria, the differences in ratings were related primarily to the clinical
      factors used by each panel. These findings support the review of appropriateness
      criteria, and other forms of clinical guidelines, to ensure that they are current
      with the clinical evidence before using them to assess clinical care. Developing
      such criteria using a multinational panel, in contrast to multiple single country
      panels, would be a more efficient use of resources.

PMID- 11954680
TI  - Patient satisfaction with availability of general practice: an international
      comparison.
AB  - OBJECTIVE: To identify associations between the characteristics of general
      practitioners and practices, and patients' evaluations of the availability of
      general practice. DESIGN: Written surveys completed by patients. SETTING: General
      practice care in nine European countries: Denmark, Germany, The Netherlands,
      Norway, UK, Belgium (Flanders and Wallonia), Switzerland, Slovenia and Spain.
      STUDY PARTICIPANTS: 15996 adult patients consecutively visiting the general
      practitioner (response rates per country varied between 47 and 89%). MAIN
      MEASURES: The Europep instrument to assess patients' evaluations of five aspects
      of the availability of general practice care: (1) getting an appointment, (2)
      getting through on the phone, (3) being able to speak to the practitioner on the
      telephone, (4) waiting time in the waiting room, and (5) providing quick services
      for urgent health problems. Each general practitioner recorded age, sex, number
      of years in the practice, number of practitioners and other care providers in the
      practice, and urbanization level of the practice. RESULTS: Patients' more
      positive evaluations were associated with fewer general practitioners in the
      practice, except for quick services for urgent health problems (range of
      conditional overall odds ratios, 1.69-2.02). In addition, a number of significant
      unconditional overall odds ratios were found, particularly those related to the
      number of general practitioners' working hours and the number of care providers
      in the practice. None of the associations was found consistently in all
      countries. CONCLUSION: Patients favour small practices and full-time general
      practitioners, which contradicts developments in general practice in many
      countries. Policy makers should consider how the tensions between patients' views
      and organizational developments can be solved.

PMID- 11954681
TI  - In-patient interventions supported by results of randomized controlled trials in
      Japan.
AB  - OBJECTIVE: To determine to what extent the results of randomized controlled
      trials (RCTs) support medical interventions for in-patients at the department of
      general medicine of a university hospital in Japan. DESIGN: Retrospective
      analysis. By reviewing discharge summaries, two physicians first independently
      decided on patients' respective primary problems at admission and up to two
      secondary problems. Next, up to five interventions for the primary problem and
      one intervention for each of the secondary problems were selected. Differences of
      opinion (if any) between the two physicians regarding these selected
      interventions were resolved by discussion. MEDLINE and/or the Cochrane Library
      were used as data sources for literature regarding the selected interventions.
      SETTING: A ward of the department of general medicine of a Japanese university
      hospital, 1995-1997. MAIN MEASURES: The proportion of therapeutic interventions
      supported by RCT results and associated meta-analyses. RESULTS: For the primary
      problems, 103 (48.8%) of the 211 most important interventions were supported by
      the results of RCTs, as were 47.8% of all the interventions including the most
      important and the adjunctive ones. Furthermore, 56.2% of the most important
      interventions for the secondary problems were also supported by the RCT results.
      CONCLUSIONS: Approximately half of the therapeutic interventions performed at an
      academic medical in-patient unit in Japan were RCT-supported. This was true not
      only for the most important interventions for primary problems but also for the
      adjunct interventions for the primary problems and the interventions for
      secondary problems.

PMID- 11954682
TI  - Availability and usability of data for medical practice assessment.
AB  - OBJECTIVE: We analyzed availability and usability of the electronic patient data
      required for assessment of medical practice for a specific patient group. DESIGN:
      Case study in which physicians defined performance indicators and additional
      exploratory information. Data availability in the hospital information system was
      determined. Data usability was evaluated based on reason for recording,
      administrative procedures, and comparison with paper data. SETTING: A 155 bed
      pediatric department in a public academic medical center. STUDY PARTICIPANTS:
      Pediatricians and children with suspected meningitis. MAIN OUTCOME MEASURES:
      Availability and usability of electronic patient data. Usability criteria were
      standardization, completeness, and accuracy. RESULTS: A total of 14 performance
      indicators were defined. Of 39 data items required for indicator quantification,
      29 were available, and 19 were usable without manual handling. Completeness and
      accuracy of the registration of reason for admission and discharge diagnoses were
      insufficient, leading to problematic patient selection and complication
      detection. Time-points of patient events were inaccurate or not available. Data
      regarding outpatient diagnosis, signs and symptoms, indications for test
      ordering, and medication administration were missing. Test result reports were
      not adequately standardized. Based on electronic patient data, five out of 14
      performance indicators could be quantified reliably, but only after patient
      selection problems were overcome. For exploratory information, 16 out of 25
      required data items were available and 13 were usable. CONCLUSIONS: Availability
      and usability of electronic patient data are insufficient for physician-led and
      detailed assessment of medical practice for specific patient groups. Extended
      registration of the reason for admission will improve patient selection and
      assessment of diagnostic process.

PMID- 11954683
TI  - Developing standards of care: a tale of two panels.
AB  - OBJECTIVE: How will a group of experts convened to develop standards of care
      communicate in meaningfully different ways when interacting online in contrast to
      traditional face-to-face meetings. Furthermore, does online interaction
      facilitate discussion among participants from diverse cultural backgrounds and at
      what cost? DESIGN: A project to develop standards of care for deaf and hard of
      hearing adults used two panels of experts operating in two different formats:
      online and face-to-face. One panel interacted via an online system while the
      other met in a day-long face-to-face conference. As one component of the project,
      we tracked the interactions of these two groups in order to describe and contrast
      their group processes. STUDY PARTICIPANTS: The subjects were volunteer experts in
      hearing impairment and health care, from organizations across the United States.
      They were a geographically diverse group with widely varying communication needs.
      We applied two different systems for facilitating communication among culturally
      diverse participants, and assessed interaction and satisfaction. MAIN OUTCOME
      MEASURES: Data were collected on the two groups on the pattern of interactions,
      satisfaction with the process, and satisfaction with outcomes. RESULTS: The
      results showed a high level of user satisfaction with both process and outcomes,
      and provide data for a description of the source of user satisfaction and the
      management of the groups. CONCLUSION: Online interaction offers unique advantages
      but poses unique management requirements for success.

PMID- 11954684
TI  - Patient compliance with managed care emergency department referral: an
      orthopaedic view.
AB  - OBJECTIVE: Patient compliance with emergency department (ED)-generated referral
      is an important part of the delivery of quality health care. Although many
      studies from non-managed care health centers have reported on ED patient
      compliance, no studies have reported on this in a managed care setting. The
      objective of this study is to examine patient compliance with ED-generated
      referral and to produce a benchmark of follow-up rates possible in a capitated
      managed care system. That is to say, in a health care system whose members pay a
      uniform per capita payment or fee, one that has salaried physicians, owns its own
      hospitals, and has a mechanism of transition from ED to outpatient clinic that
      ensures referral accessibility. DESIGN: Retrospective review of consecutive ED
      patient compliance with ED-generated referral. PATIENTS/METHODS: All consecutive
      patients who presented to a managed care hospital's ED with an acute fracture and
      who were given an outpatient referral during the period from 23rd December 1998
      to 23rd January, 1999. Of 8000 consecutive ED patients, 234 were included in the
      study. Compliance with ED-generated referral was determined from outpatient
      clinic records. RESULTS: Of the 234 patients treated in the ED and referred, 222
      (94.9%) complied with follow-up appointments. CONCLUSIONS: We have demonstrated
      that an ED patient follow-up compliance rate of 94.9% can be obtained. It is
      probable that the high compliance rate is due to the features of the system
      studied. The high rate may also be related to the specific diagnosis studied,
      although previous literature reports poor ED patient compliance for the same
      diagnosis in a different ED setting. Additional research is needed to determine
      whether the high compliance rate reported in this study can be obtained in ED
      settings that are not part of a similar managed care system and to determine the
      role of referral accessibility (or inaccessibility) in current ED settings.

PMID- 11954685
TI  - Hospital quality information for patients in Taiwan: can they understand it?
AB  - OBJECTIVES: To investigate Taiwanese patients' ability to judge hospital quality
      and to examine their knowledge of commonly used quality indicators. DESIGN:
      Survey of patients during their stay in hospital. SETTING: Internal medicine,
      surgery, and gynecology wards in seven hospitals in northern Taiwan.
      PARTICIPANTS: Sample of 661 patients who voluntarily completed a questionnaire.
      MAIN OUTCOME MEASURES: (1) Patients' ability to judge hospital quality in
      relation to medical equipment, technical competence, and medication; (2)
      patients' knowledge of seven quality indicators: patient satisfaction, hospital
      acquired infection, accreditation level, percent specialists, malpractice claims,
      unscheduled readmission, and mortality rate 48 hours after surgery. RESULTS: A
      total of 31-50% of the participants claimed that they could judge a hospital's
      quality on the basis of medical equipment, technical competence, or medication.
      The most frequently mentioned reasons on which their judgments were based were
      related to their own experiences and to the hospital's reputation. The percentage
      of participants reporting that they understood the quality indicators was 6.7
      42.1%. CONCLUSION: In general, patients lack the ability to judge hospital
      quality and are unfamiliar with the commonly used quality indicators. Public
      education should be enhanced, or more understandable indicators should be
      developed in the future.

PMID- 11954686
TI  - The future of quality leadership.

PMID- 11954687
TI  - A review of the 'welfare state' and alternative ways of delivering health care.
AB  - There was no such thing as a public policy for quality health care in the
      inception of what we now address as the 'welfare state'. The main objectives of
      those supporting the idea, epitomized by the 'freedom from want' that Beveridge
      postulated in his now famous November 1942 Report on Social Insurance and Allied
      Services, was to extend the benefits of social insurance, that is access to
      services such as health care, to every individual. In the same fashion, post
      World War II initiatives in Latin America somewhat disregarded the intrinsic
      quality of health care services, provided they were distributed equally, at least
      among the urban people. Therefore, it is licit to ascertain that the main, albeit
      implicit, quality feature of health care was access, that is the ability to reach
      the entire population with the available services. The health care reform
      movement following the welfare state crisis, from the Jackson Hole group and
      Einthoven's managed competition in the United States to the internal markets
      proposals in different European countries, started when universal coverage had
      been achieved where it had been pursued, and disregarded elsewhere. In other
      words, access as a measure of health care quality was not the point. Instead, the
      subject of both academic research and administrative initiatives was the quality
      of the health services effectively provided to the population. Furthermore, the
      World Health Organization in its World Health Report 2000 explicitly excluded
      access as an item to be assessed in the process of evaluating health systems,
      although many countries had not achieved, nor were even near, universal coverage.
      Therefore, notwithstanding the relevance of the continuous quality improvement of
      the health services actually delivered to the people, access should always be the
      first quality concern to those health systems lacking universal coverage of the
      population they are supposed to serve.

PMID- 11954688
TI  - Community-based integrated care: myth or must?
AB  - ISSUE: In spite of the many efforts that have been made to rationalize and
      improve the functioning and the quality of health care delivery in industrialized
      countries, too limited a degree of success has been achieved so far. This paper
      argues that this limited success originates from a lack of coherence among the
      various strategies and instruments developed to rationalize and improve the
      delivery of health care. ADDRESSING THE ISSUE: This fact can be shown by reducing
      the complexity of today's health care into three levels of decision making: the
      primary process of patient care, the organizational context, and the financing
      and policy context of health care systems. Distinct rationales exist on each of
      these three levels of decision making as actors have their own perspectives,
      cultures, disciplines, and traditions concerning the delivery of health care.
      These differences can often result in ambiguity of goals, conflicting interests
      between decision makers, bureaucracy, poor information transfer, and limited use
      of the available scientific knowledge on all three levels. In such a context,
      rationalization and quality-improvement efforts are frustrated and will have
      limited effectiveness. Therefore, the various rationalization strategies and
      instruments on all three levels of decision making should be embedded in our
      health care systems in a synergistic way. DEMONSTRATING THE PROPOSED SOLUTION:
      Community-based integrated care is a promising approach to addressing this issue
      successfully. How this concept might function as a unifying concept for quality
      improvement will be illustrated by relevant developments in the Academic Medical
      Center, University of Amsterdam in The Netherlands.

PMID- 11954689
TI  - Charles Wheatstone (1802-1875).

PMID- 11954690
TI  - Visual feature binding in early infancy.
AB  - How does the developing brain of the human infant solve the feature-binding
      problem when visual stimuli consisting of multiple colored objects are presented?
      A habituation--dishabituation procedure revealed that 1-month-old infants have
      the ability to discriminate changes in the conjunction of a familiar shape and
      color in two objects. However, this good earlier performance was followed by
      poorer performance at 2 months of age. The performance improved again at 3 months
      of age. Detailed analysis of the oculomotor behaviors revealed that the age of 2
      months was a period of drastic transition when the tendency to stay with the
      fixated objects disappeared and repetitive saccades between the two objects
      emerged. Our findings suggest that the ability to perceive conjunctions of
      features is available to infants very early, that the perceptual/neural basis at
      1 and at 3 months of age may be fundamentally different, and that feature
      integration by vigorous eye movements or selective attention may be the key
      functional difference between the age groups.

PMID- 11954691
TI  - Is there a linear or a nonlinear relationship between rotation and configural
      processing of faces?
AB  - Research suggests that inverted faces are harder to recognise than upright faces
      because of a disruption in processing their configural properties. Reasons for
      this difficulty were explored by investigating people's ability to identify faces
      at intermediate angles of rotation. Participants were asked to discriminate
      blurred famous and unfamiliar faces presented at nine angles. Blurred faces were
      used to minimise featural processing strategies, and to assess the effects of
      rotation that are specific to configural processing. The results indicate a
      linear relationship between angle of rotation and recognition accuracy. It
      appears that configural processing becomes gradually more disrupted the further a
      face is oriented away from the upright. The implications of these findings for
      competing explanations of the face-inversion effect are discussed.

PMID- 11954692
TI  - The priming of face recognition after metric transformations.
AB  - Four experiments were performed to test whether the perceptual priming of face
      recognition would show invariance to changes in size, position, reflectional
      orientation (mirror reversal), and picture-plane rotation. In all experiments,
      subjects recognized faces in two blocks of trials; in the second block, some of
      the faces were identical to those in the first, and others had undergone metric
      transformations. The results show that subjects were equally fast to recognize
      faces whether or not the faces had changed in size, position, or reflectional
      orientation between the first and second presentations of the faces. In contrast,
      subjects were slower to recognize both faces and objects when they were planar
      rotated between the first and second presentations. The results suggest that the
      same metric invariances are shown by both face recognition and basic-level object
      recognition.

PMID- 11954693
TI  - Are average and symmetric faces attractive to infants? Discrimination and looking
      preferences.
AB  - Young infants prefer to look at faces that adults find attractive, suggesting a
      biological basis for some face preferences. However, the basis for infant
      preferences is not known. Adults find average and symmetric faces attractive. We
      examined whether 5-8-month-old infants discriminate between different levels of
      averageness and symmetry in faces, and whether they prefer to look at faces with
      higher levels of these traits. Each infant saw 24 pairs of female faces. Each
      pair consisted of two versions of the same face differing either in averageness
      (12 pairs) or symmetry (12 pairs). Data from the mothers confirmed that adults
      preferred the more average and more symmetric versions in each pair. The infants
      were sensitive to differences in both averageness and symmetry, but showed no
      looking preference for the more average or more symmetric versions. On the
      contrary, longest looks were significantly longer for the less average versions,
      and both longest looks and first looks were marginally longer for the less
      symmetric versions. Mean looking times were also longer for the less average and
      less symmetric versions, but those differences were not significant. We suggest
      that the infant looking behaviour may reflect a novelty preference rather than an
      aesthetic preference.

PMID- 11954694
TI  - Separating perception time from response time: the slope transition paradigm.
AB  - This paper describes the slope transition paradigm (STP), a variant of rapid
      serial visual presentation (RSVP) that separates early (perceptual) processing
      time from total response time. The paradigm is based on a very simple idea:
      provide varying amounts of time for perceptual processing and find the moment
      when the subject begins to waste time waiting for more data. That moment is a
      measure of how much time was actually needed. The method was used in two
      experiments. Results are discussed in relation to set-size effects, perceptual
      capacity limits, attentional dwell times, and some related neurophysiological
      findings. The method appears to tap aspects of information processing that differ
      from those tapped in studies of the psychological refractory period, the
      attentional blink, and repetition blindness.

PMID- 11954695
TI  - Global interference: the effect of exposure duration that is substituted for
      spatial frequency.
AB  - In this study, participants were required to identify hierarchically structured
      patterns that appeared at either global or local level. Paquet and Merikle (1984
      Canadian Journal of Psychology 381 45-53) showed that global interference is
      affected by exposure duration in the processing of a hierarchical structure. They
      showed that only global-to-local interference occurred at short exposure
      durations. In contrast, global-to-local as well as local-to-global interference
      was observed at long exposure durations. They suggested that the effect of
      exposure duration with global interference depends on the high-spatial-frequency
      versus low-spatial-frequency channel. In the present study, exposure duration
      (short or long) was varied randomly from trial to trial (experiment 1), or held
      constant (experiment 2). In experiment 1, global-to-local interference occurred
      at both short and long exposure durations, even though the same physical
      properties existed as in experiment 2. In experiment 2, both global-to-local and
      local-to-global interference occurred at only long exposure durations, in line
      with the results reported by Paquet and Merikle. This suggests that the effect of
      exposure duration on global interference is explained not only by spatial
      frequency channels, but also by attentional shift.

PMID- 11954696
TI  - Path integration from optic flow and body senses in a homing task.
AB  - We examined the roles of information from optic flow and body senses (eg
      vestibular and proprioceptive information) for path integration, using a triangle
      completion task in a virtual environment. In two experiments, the contribution of
      optic flow was isolated by using a joystick control. Five circular arenas were
      used for testing: (B) both floor and wall texture; (F) floor texture only,
      reducing information for rotation; (W) wall texture only, reducing information
      for translation; (N) a no texture control condition, and (P) an array of posts.
      The results indicate that humans can use optic flow for path integration and are
      differentially influenced by rotational and translational flow. In a third
      experiment, participants actively walked in arenas B, F, and N, so body senses
      were also available. Performance shifted from a pattern of underturning to
      overturning and exhibited decreased variability, similar responses with and
      without optic flow, and no attrition. The results indicate that path integration
      can be performed by integrating optic flow, but when information from body senses
      is available it appears to dominate.

PMID- 11954697
TI  - Polysomnographic pattern recognition for automated classification of sleep-waking
      states in infants.
AB  - A robust, automated pattern recognition system for polysomnography data targeted
      to the sleep-waking state and stage identification is presented. Five patterns
      were searched for: slow-delta and theta wave predominance in the background
      electro-encephalogram (EEG) activity; presence of sleep spindles in the EEG;
      presence of rapid eye movements in an electro-oculogram; and presence of muscle
      tone in an electromyogram. The performance of the automated system was measured
      indirectly by evaluating sleep staging, based on the experts' accepted
      methodology, to relate the detected patterns in infants over four months of post
      term age. The set of sleep-waking classes included wakefulness, REM sleep and non
      REM sleep stages I, II, and III-IV. Several noise and artifact rejection methods
      were implemented, including filters, fuzzy quality indices, windows of variable
      sizes and detectors of limb movements and wakefulness. Eleven polysomnographic
      recordings of healthy infants were studied. The ages of the subjects ranged from
      6 to 13 months old. Six recordings counting 2665 epochs were included in the
      training set. Results on a test set (2,369 epochs from five recordings) show an
      overall agreement of 87.7% (kappa 0.840) between the automated system and the
      human expert. These results show significant improvements compared with previous
      work.

PMID- 11954698
TI  - Experimental and numerical studies on convective heat transfer in a neonatal
      incubator.
AB  - Thermo-neutrality is one of the major environmental factors affecting a premature
      or low-birth-weight neonate inside an incubator. Severe temperature differences
      inside an incubator lead to neonate heat loss, hypothermia and apnoea, which are
      closely related to air flow and air velocity. In the study, flow visualisations,
      hot-wire velocity measurements and computational fluid dynamics simulate the
      airflow inside a neonatal incubator. An anatomically correct neonate model is
      designed using a three-dimensional laser scanner system and a rapid prototyping
      machine. Flow visualisations demonstrate that large-scale rotating airflow is
      produced inside the chamber, and a number of small, stationary eddies are found
      in regions between the air inlet and the neonate. Hot-wire measurements show that
      air velocities along the long inlets are not uniform. Computational fluid
      dynamics show relatively uniform temperatures of about 34 degrees C on the
      neonate's anterior aspect and the highest temperature of 36.1 degrees C at the
      right armpit and the crotch. Flow fields from airflow visualisations, hot-wire
      measurements and computational fluid dynamics are very similar, both
      qualitatively and quantitatively. The small eddies produced between the neonate
      and the mattress could interfere with convective and evaporative heat transfers
      from the neonate. Therefore it is important to eliminate eddies around the
      neonate in future designs of neonatal incubators.

PMID- 11954699
TI  - Two-electrode biopotential amplifier with current-driven inputs.
AB  - A circuit was developed for a differential two-electrode biopotential amplifier.
      Current sources at the amplifier inputs were controlled by the common-mode
      voltage. This principle is well known in telephony for interfacing the telephone
      line with analogue-type phones. A low impedance of about 1 k(ohm) was obtained
      between each input and the common point of the circuit. The differential input
      impedance of 60 M(ohm) was obtained with the use of precision resistors.
      Considerable reduction in the common-mode voltages of more than 200 times
      resulted. The circuit can be useful for biosignal acquisition from subjects in
      areas of very high electromagnetic fields, where high common-mode voltages could
      saturate the input amplifier stages.

PMID- 11954700
TI  - Pain model and fuzzy logic patient-controlled analgesia in shock-wave
      lithotripsy.
AB  - Pain control in conscious patients was investigated using a push-button, demand
      driven supply of drugs. A fuzzy logic patient-controlled analgesia (PCA)
      algorithm was compared with a conventional algorithm, for alfentanil
      administration in extracorporeal shock-wave lithotripsy. The conventional PCA
      algorithm used an initial dose of 0.25mg, a fixed infusion rate of 60 mg h(-1)
      and a fixed bolus size of 0.2 mg with a 1 min lockout. The fuzzy logic PCA
      algorithm used an initial dose of 0.25 mg, a changeable infusion rate and a bolus
      size of 0.1 or 0.05 mg. The infusion rate was adjusted according to a look-up
      table that accepted the button-pressing history over the last three lockout
      intervals. The look-up table was designed using fuzzy logic. The bolus size was
      adjusted according to the button-pressing history over the past two lockout
      intervals. Twelve patients were treated using conventional PCA, and thirteen were
      treated with PCA + fuzzy logic control (FLC). PCA + FLC patients consumed 45%
      less drug. Also, PCA + FLC patients had a mean delivery/demand ratio of 82%,
      compared with 60% in conventional PCA. When the pain intensity scale was
      analysed, PCA + FLC patients had acceptable pain intensity at 62%, compared with
      44% in conventional PCA.

PMID- 11954702
TI  - Biomechanical model to simulate tissue differentiation and bone regeneration:
      application to fracture healing.
AB  - Bone regeneration is a common biological process occurring, for example, during
      fracture healing or osseo-integration of prostheses. Computer simulation of bone
      regeneration is difficult to carry out because it is a complex sequence of cell
      mediated processes regulated by mechanobiological stimuli. An algorithm to
      predict the time-course of intramembranous and endochondral ossification has been
      developed. The algorithm assumes that there are precursor cells in the
      undifferentiated tissue and that these cells differentiate into either
      fibroblasts (to form fibrous connective tissue), chondrocytes (to form
      cartilaginous tissue) or osteoblasts (to form bone), based on a combination of
      biophysical stimuli derived from strain in the collagenous matrix and flow of the
      interstitial fluid. Both these stimuli are known to deform the precursor cells,
      and the authors hypothesise that this causes activation of cell differentiation
      pathways. The observation that precursor cells take time to spread throughout the
      fracture callus has been included in the algorithm. The algorithm was tested in
      an investigation of the fracture healing of a long bone using an axi-symmetric
      finite element model. The spatio-temporal sequence of tissue phenotypes that
      appear in the course of fracture healing was successfully simulated. Furthermore,
      the origin of the precursor cells (either surrounding muscle, bone marrow or
      periosteum) was predicted to have a fundamental effect on the healing pattern and
      on the rate of reduction of the interfragmentary strain (IFS). The initial IFS =
      0.15 drops to 0.01 within seven iterations if cells originated from the
      surrounding soft tissue, but took more than 50% longer if cells originated in the
      inner cambium layer of the periosteum, and four times longer if precursor cells
      originated from the bone marrow only.

PMID- 11954701
TI  - Gradual potentiation of isometric muscle force during constant electrical
      stimulation.
AB  - An investigation was carried out into how stimulation frequency and stimulation
      history affect the potentiation of muscle force during 20s of constant
      stimulation of the two knee extensors in isometric conditions. Stimulation
      frequency significantly affected the potentiation pattern: low-frequency (2.5-10
      Hz) stimulation showed a reduction and subsequent enhancement of force, and high
      frequency (14.3-25 Hz) stimulation showed only enhancement of force. The degree
      of enhancement in force and time-to-peak decreased with the stimulation
      frequency. Whereas 40 Hz conditioning stimulation enhanced the muscle force, 14
      Hz stimulation after 10s of rest induced little force enhancement (8% in both
      muscles). When the frequency of the conditioning stimulation was 14 Hz and the
      main 14 Hz stimulation was applied after 50s of rest, the initial force at the
      main stimulation was similar to the final force value of the conditioning
      stimulation (above 90% similarity). The potentiated twitch force slowly decayed
      during rest, with an average time constant of 2.4 min. These observations
      indicate that muscle potentiation depends on the stimulation frequency and
      stimulation history, and therefore a computer model of potentiation can play an
      important role in predicting muscle force and body movement induced by electrical
      stimulation.

PMID- 11954703
TI  - Progress towards automated diabetic ocular screening: a review of image analysis
      and intelligent systems for diabetic retinopathy.
AB  - Patients with diabetes require annual screening for effective timing of sight
      saving treatment. However, the lack of screening and the shortage of
      ophthalmologists limit the ocular health care available. This is stimulating
      research into automated analysis of the reflectance images of the ocular fundus.
      Publications applicable to the automated screening of diabetic retinopathy are
      summarised. The review has been structured to mimic some of the processes that an
      ophthalmologist performs when examining the retina. Thus image processing tasks,
      such as vessel and lesion location, are reviewed before any intelligent or
      automated systems. Most research has been undertaken in identification of the
      retinal vasculature and analysis of early pathological changes. Progress has been
      made in the identification of the retinal vasculature and the more common
      pathological features, such as small aneurysms and exudates. Ancillary research
      into image preprocessing has also been identified. In summary, the advent of
      digital data sets has made image analysis more accessible, although questions
      regarding the assessment of individual algorithms and whole systems are only just
      being addressed.

PMID- 11954704
TI  - Kinematic analysis of mobile-bearing and fixed-bearing knee prostheses by
      simulation.
AB  - The object of the study was to model fixed-bearing knee prostheses (FBKs) and
      mobile-bearing knee prostheses (MBKs) during weight-bearing deep knee bends and
      to analyse and compare the kinematics of the two prosthesis types. To obtain
      quantitative data, an overall model of a leg was constructed, and this included a
      three-dimensional model of the tibiofemoral joint and simplified two-dimensional
      models of the ankle and patellofemoral joint. The simulated movement pattern of
      the tibiofemoral contact point in the FBK was analysed to show the posterior
      contact position on the tibia at full extension and anterior translation as the
      knee was flexed from 30 degrees to 90 degrees. The simulated maximum
      displacements of the medial and lateral contact positions of the FBK were 5.6 and
      6.2 mm, respectively. These results were almost in agreement with experimental
      studies. Compared with the FBK, the movement pattern of the tibiofemoral contact
      point in the MBK for the anterior contact position on the tibia at full extension
      and posterior translation, with respect to the tibia as the knee was flexed, gave
      results closer to those of the normal knee. The simulated displacements of the
      medial and lateral contact positions of the MBK with respect to the tibia were
      9.0 and 13.0 mm from full extension to 90 degrees flexion, respectively. The
      difference in the kinematic results between the FBK and the MBK could be
      accounted for by movement of the insert and the larger force of the posterior
      cruciate ligament on the MBK.

PMID- 11954705
TI  - Changes in electrical resistivity of swine liver after occlusion and postmortem.
AB  - The resistivity of swine liver tissue was measured in vivo, during induced
      ischaemia and post-mortem, so that associated changes in resistivity could be
      quantified. Plunge electrodes, the four-terminal method and a computer-automated
      measurement system were used to acquire resistivities between 10Hz and 1 MHz.
      Liver resistivity was measured in vivo in three animals at 11 locations. At 10
      Hz, resistivity was 758 +/- 170 ohm x cm. At 1 MHz, the resistivity was 250 +/-
      40 ohm x cm. The resistivity time course was measured during the first 10 min
      after the liver blood supply in one animal had been occluded. Resistivity
      increased steadily during occlusion. The change in resistivity of an excised
      tissue sample was measured during the first 12h after excision in one animal.
      Resistivity increased during the first 2h by 53% at 10 Hz and by 32% at 1 MHz.
      After 2h, resistivity decreased, probably owing to membrane breakdown. The
      resistivity data were fitted to a Cole-Cole circle, from which extracellular
      resistance Re, intracellular resistance Ri and cell membrane capacitance Cm were
      estimated. Re increased during the first 2h by 95% and then decreased, suggesting
      an increase in extracellular volume. Cm increased during the first 4 h by 40%,
      possibly owing to closure of membrane channels, and then decreased, suggesting
      membrane breakdown. Ri stayed constant during the initial 6h and then increased.

PMID- 11954706
TI  - Modification of the wavelet method used in transiently evoked otoacoustic
      emission pass/fail criterion to increase its accuracy.
AB  - Transiently evoked otoacoustic emissions (TEOAEs) are widely used in newborn
      hearing screening programmes for early detection of hearing losses. To increase
      the accuracy of a TEOAE pass/fail criterion that uses the wavelet method, it was
      demonstrated that the large estimation variance is a possible reason for the
      inaccuracy, and a modified wavelet method is proposed to solve the inaccuracy
      problem. In the modified wavelet method, N paired buffers, instead of only one,
      were used to store the total 512 subaveraged responses, and then the average of
      the calculated N cross-correlation coefficients between N pairs of TEOAE signals
      was taken in the pass/fail criterion. Four sets of 256 synthesised noise and
      eight sets of 256 synthesised noisy TEOAE signals were tested, and each set was
      tested 1,000 times. The results showed that the standard deviation of the
      correlation estimation was greatly reduced by using this average value with N
      selected as 4. As a result, the total number of single-scale cross-correlation
      coefficients below 50% decreased from 1281 to 195 for noisy TEOAE signals, and
      the total number of single-scale cross-correlation coefficients above 50%
      decreased from 90 to 0 for synthesised noise.

PMID- 11954707
TI  - Conversion of left ventricular endocardial positions from patient-independent co
      ordinates into biplane fluoroscopic projections.
AB  - Electrocardiographic body surface mapping is used clinically to guide catheter
      ablation of cardiac arrhythmias by providing an estimate of the site of origin of
      an arrhythmia. The localisation methods used in our group produce results in left
      ventricular cylinder co-ordinates (LVCCs), which are patient-independent but hard
      to interpret during catheterisation in the electrophysiology laboratory. It is
      preferable to provide these results as three-dimensional (3D) co-ordinates which
      can be presented as projections in the biplane fluoroscopic views that are used
      routinely to monitor the catheter position. Investigations were carried out into
      how well LVCCs can be converted into fluoroscopic projections with the limited
      anatomical data available in contemporary clinical practice. Endocardial surfaces
      from magnetic resonance imaging (MRI) scans of 24 healthy volunteers were used to
      create an appropriate model of the left-ventricular endocardial wall. Methods for
      estimation of model parameters from biplane fluoroscopic images were evaluated
      using simulated biplane data created from these surfaces. In addition, the
      conversion method was evaluated, using 107 catheter positions obtained from eight
      patients, by computing LVCCs from biplane fluoroscopic images and reconstructing
      the 3D positions using the model. The median 3D distance between reconstructed
      positions and measured positions was 4.3mm.

PMID- 11954709
TI  - Measure of synchronisation of right atrial depolarisation wavefronts during
      atrial fibrillation.
AB  - A new index of synchronisation (IS) between the electrical activity of pairs of
      close atrial sites during atrial fibrillation (AF) is introduced. The index
      assesses the probability of finding synchronous activations in intra-atrial
      bipolar electrograms and is based on the assumption that two activations closely
      spaced in time are likely to belong to the same depolarisation wavefront. A
      dedicated statistical treatment to test this hypothesis is also illustrated.
      Experimental data were obtained using a multipolar basket catheter in the right
      atrium in 20 patients during normal sinus rhythm (NSR), atrial flutter (AFL, one
      patient), high-frequency pacing (HFP, two patients) and chronic AF (17 patients),
      and 30 segments were obtained from each. From the 24 pairs of bipoles, a single
      averaged IS and its standard deviation were extracted. The IS was 1 in NSR and
      HFP and 0.95 +/- 0.02 during AFL. During AF, the IS provided a quantitative
      measure of the degree of coupling of various atrial sites. The IS varied
      significantly among the recording sites (range 0.38-0.96), showing a patient
      dependent pattern, and decreased as the arrhythmia complexity increases. No
      temporal trends were observed for the IS values in any chronic AF patient. On
      average, in each site, the dispersion of the IS over time was lower than 32% of
      the mean, for all patients. Additional relevant features of the proposed index
      are its high temporal resolution (2s) and robustness to activation time
      estimation error, to missing or false detections and to the ever-changing pattern
      of propagation. The index of synchronisation is a descriptor of the
      electrophysiological properties of atrial tissues.

PMID- 11954708
TI  - Modelling induction of a rotor in cardiac muscle by perpendicular electric
      shocks.
AB  - A strong, properly timed shock applied perpendicularly to a propagating wavefront
      causes a rotor in the canine myocardium. Experimental data indicate that the
      induction of this rotor relies on the shock exciting tissue away from the
      electrodes. The computational study reproduced such direct excitation in a two
      dimensional model of a 2.7 x 3 cm sheet of cardiac muscle. The model used
      experimentally measured extracellular potentials to represent 100 and 150 V
      shocks delivered through extracellular electrodes. The shock-induced
      transmembrane potential was computed according to two mechanisms, the activating
      function and the unit-bundle sawtooth potential. The overall process leading to
      initiation of a rotor was the same in model and experiment. For the 100 V shock,
      the directly excited region extended 2.26 cm away from the electrode; the centre
      of the rotor ('critical point') was 1.28 cm away, where the electric field Ecr
      was 4.54 Vcm(-1). Increasing the shock strength to 150 V moved the critical point
      1.02 cm further and decreased Ecr by 0.39 Vcm(-1). The results are comparable
      with experimental data. The model suggests that the unit-bundle sawtooth is
      responsible for the creation of the directly excited region, and the activating
      function is behind the dependence of Ecr on shock strength.

PMID- 11954710
TI  - Automatic P-wave analysis of patients prone to atrial fibrillation.
AB  - A method is presented for automatic analysis of the P-wave, based on lead II of a
      12-lead standard ECG, in resting conditions during a routine examination for the
      detection of patients prone to atrial fibrillation (AF), one of the most
      prevalent arrhythmias. First, the P-wave was delineated, and this was achieved in
      two steps: the detection of the QRS complexes for ECG segmentation, using a
      wavelet analysis method, and a hidden Markov model to represent one beat of the
      signal for P-wave isolation. Then, a set of parameters to detect patients prone
      to AF was calculated from the P-wave. The detection efficiency was validated on
      an ECG database of 145 patients, including a control group of 63 people and a
      study group of 82 patients with documented AF. A discriminant analysis was
      applied, and the results obtained showed a specificity and a sensitivity between
      65% and 70%.

PMID- 11954711
TI  - Wavelet transform analysis of heart rate variability during myocardial ischaemia.
AB  - Analysis of heart rate variability (HRV) is a valuable, non-invasive method for
      quantifying autonomic cardiac control in humans. Frequency-domain analysis of HRV
      involving myocardial ischaemic episodes should take into account its non
      stationary behaviour. The wavelet transform is an alternative tool for the
      analysis of non-stationary signals. Fourteen patients have been analysed, ranging
      from 40 to 64 years old and selected from the European Electrocardiographic ST-T
      Database (ESDB). These records contain 33 ST episodes, according to the notation
      of the ESDB, with durations of between 40s and 12 min. A method for analysing HRV
      signals using the wavelet transform was applied to obtain a time-scale
      representation for very low-frequency (VLF), low-frequency (LF) and high
      frequency (HF) bands using the orthogonal multiresolution pyramidal algorithm.
      The design and implementation using fast algorithms included a specially adapted
      decomposition quadrature mirror filter bank for the frequency bands of interest.
      Comparing a normality zone against the ischaemic episode in the same record,
      increases in LF (0.0112 +/- 0.0101 against 0.0175 +/- 0.0208 s2 Hz(-1); p<0.1)
      and HF (0.0011 +/- 0.0008 against 0.00 17 +/- 0.0020 s2 Hz(-1); p<0.05) were
      obtained. The possibility of using these indexes to develop an ischaemic-episode
      classifier was also tested. Results suggest that wavelet analysis provides useful
      information for the assessment of dynamic changes and patterns of HRV during
      myocardial ischaemia.

PMID- 11954712
TI  - New criteria for estimating baroreflex sensitivity using the transfer function
      method.
AB  - Computer simulations were carried out to appraise three new criteria for the
      estimation of baroreflex sensitivity (BRS) using the transfer function method.
      The major goal was to identify a computation procedure able to overcome the
      intrinsic limitations of the classical coherence criterion. Four representative
      shapes of the gain function and three different average gains (2, 5 and 8
      ms(mmHg)(-1) in the low-frequency (LF) band (0.04-0.15Hz) were considered. The
      signal-to-noise ratio was made to vary so that the peak coherence in the LF band
      changed from 0.15 to 0.9. All simulation parameters were derived from previous
      observations in healthy subjects and heart disease patients. The error of the
      estimated gain function was obtained from its confidence interval. BRS was
      computed as average gain in the LF band: (a) including in the average only those
      points having error < or = threshold (criterion 1, C1); (b) calculating the mean
      error in the band and accepting BRS measurements only when this error was < or =
      threshold (criterion 2, C2); (c) including in the average all points, regardless
      of the error (criterion 3, C3). The three criteria were compared in terms of
      measurability (percentage of measured BRS) and accuracy (bias and SD of BRS).
      Using C1 and C2, measurability dropped to 10% when the peak coherence in the LF
      band decreased, respectively, to 0.18-0.41 and to 0.26-0.53, depending on the
      shape and strength of the gain. In this condition (lower bound of measurability),
      worst bias and SD (average gain: 8 ms(mmHg)(-1)) were, respectively, 0.8
      ms(mmHg)(-1) and 3.3ms(mmHg)(-1) (C1), and 0.1 ms(mmHg)(-1) and 1.0 ms(mmHg)(-1)
      (C2). C3, by definition, always ensured 100% measurability and showed bias and SD
      comparable with, or even lower than, C1 and C2, within the common range of
      measurable BRS. In the extreme condition of 0.15 coherence, bias and SD were,
      respectively, 1.7 ms(mmHg)(-1) and 2.3ms(mmHg)(-1) (average gain: 8ms(mmHg)(-1)).
      Hence, error checking (C1 and C2) dramatically reduced measurability and did not
      improve accuracy of BRS measurements compared with performing no error check
      (C3). In conditions of low signal-to-noise ratio and/or impaired baroreflex gain,
      leading to markedly reduced coherence, the simple average of the gain function in
      the LF band allows BRS to be estimated with accuracy adequate for clinical
      purposes.

PMID- 11954713
TI  - Spectral signature and heterodyne efficiency for different wavelengths in laser
      Doppler flowmetry.
AB  - Laser Doppler perfusion monitoring and imaging technologies generate time traces
      and two-dimensional flow maps of the microcirculation. With the goal of reaching
      different tissue depths, these technologies are equipped with lasers operating at
      different wavelengths lambda. The fact that the average scattering angle, at a
      single scattering event, between a photon and a red blood cell increases with
      lambda is compensated for by a 1/lambda effect in the scattering vector,
      rendering the average frequency shift virtually independent of the choice of
      wavelength. Monte Carlo simulations showed that the corresponding spectral
      signature of the Doppler signals for lambda = 632.8 nm and 780 nm were close to
      identical. The theoretical predictions were verified by calculating the centre-of
      gravity (COG) frequency of the laser Doppler power spectral density for the two
      wavelengths from forearm and finger skin, representing a low and high perfusion
      area, respectively (forearm COG= 123 against 121 Hz, finger COG = 220 against 212
      Hz). When the wavelength changes from 632.8 nm to 780 nm, the heterodyne
      efficiency of the detector and, thereby, the inherent system amplification
      increase. For tissues with identical microvascular flow conditions, the output
      signal therefore tends to increase in magnitude when shifting to longer
      wavelengths.

PMID- 11954714
TI  - Influence of estimators of spectral density on the analysis of electromyographic
      and vibromyographic signals.
AB  - Electromyographic (EMG) and vibromyographic (VMG) signals are related to
      electrical and mechanical muscle activity, respectively. It is known that
      variations in their frequency components are related to changes in muscle
      activity and fatigue. The aims of this study were: (1) to analyse the resolution,
      variance and bias of different estimations of power spectral density function
      (PSD); and (2) to evaluate the influence of the spectral estimation method on
      three indices calculated from the PSD of EMG and VMG signals: mean (f(m)) and
      median (f(c)) frequencies and the ratio of high and low frequency components (H/L
      ratio) to select the most suitable estimator. Myographic signals were recorded
      from the sternomastoid muscle, an accessory respiratory muscle, during breathing.
      For non-parametric methods, Welch periodograms and correlograms were analysed
      with different windows. Autoregressive (AR) moving average (MA) and ARMA models
      with different orders were evaluated in the parametric methods. The
      reproducibility of the results was also studied. Frequency indices, particularly
      the H/L ratio and f(c), changed considerably when varying the following
      parameters of the estimators: periodogram with segment durations longer than 150
      ms in EMG and with any duration in VMG signals; correlogram with window length
      shorter than 10% of the total number of samples; and AR models with an order
      lower than 10, 20 and 40 in f(c), fm and H/L ratio, respectively, in both
      myographic signals.

PMID- 11954715
TI  - Coherence between one random and one periodic signal for measuring the strength
      of responses in the electro-encephalogram during sensory stimulation.
AB  - Coherence between a pulse train representing periodic stimuli and the EEG has
      been used in the objective detection of steady-state evoked potentials. This work
      aimed to quantify the strength of the stimulus responses based on the statistics
      of coherence estimate between one random and one periodic signal, focusing on the
      confidence limits and power of significance tests in detecting responses. To
      detect the responses in 95% of cases, a signal-to-noise ratio of about -7.9 dB
      was required when using 48 windows (M) in the coherence estimation. The ratio,
      however, increased to -1.2 dB when M was 12. The results were tested in Monte
      Carlo simulations and applied to EEGs obtained from 14 subjects during visual
      stimulation. The method showed differences in the strength of responses at the
      stimulus frequency and its harmonics, as well as variations between individuals
      and over cortical regions. In contrast to those from the parietal and temporal
      regions, results for the occipital region gave confidence limits (with M = 12)
      that were above zero for all subjects, indicating statistically significant
      responses. The proposed technique extends the usefulness of coherence as a
      measure of stimulus responses and allows statistical analysis that could also be
      applied usefully in a range of other biological signals.

PMID- 11954716
TI  - Plant uptake of 134Cs in relation to soil properties and time.
AB  - 134Cs uptake by sunflower and soybean plants grown on seven different soils and
      its relation to soil properties were studied in a greenhouse pot experiment. Soil
      in each pot was contaminated by dripping the 134Cs in layers, and sunflower and
      soybean plants were grown for three and two successive periods, respectively.
      134Cs plant uptake was expressed as the transfer factor (TF) (Bq kg(-1) plant/Bq
      kg(-1) soil) and as the daily plant uptake (flux) (Bq pot(-1) day(-1)) taking
      into account biomass production and growth time. For the studied soils and for
      both plants, no consistent trend of TFs with time was observed. The use of
      fluxes, in general, provided less variable results than TFs and stronger
      functional relationships. A negative power functional relationship between
      exchangeable potassium plus ammonium cations expressed as a percentage of cation
      exchange capacity of each soil and 134Cs fluxes was found for the sunflower
      plants. A similar but weaker relationship was observed for soybean plants. The
      significant correlation between sunflower and soybean TFs and fluxes, as well as
      the almost identical highest/lowest 134Cs flux ratios, in the studied soils,
      indicated a similar effect of soil characteristics on 134Cs uptake by both
      plants. In all the studied soils, sunflower 134Cs TFs and fluxes were
      significantly higher than the respective soybean values, while no significant
      difference was observed in potassium content and daily potassium plant uptake
      (flux) of the two plants.

PMID- 11954717
TI  - Suspended particle adhesion on aquatic plant surfaces: implications for 137Cs and
      133Cs uptake rates and water-to-plant concentration ratios.
AB  - Suspended particle adhesion on aquatic biota can significantly increase the
      apparent concentration of radionuclides above their endogenous value, leading to
      an overestimation of the uptake rate and concentration ratios. This study is an
      attempt to assess quantitatively the importance of suspended particle adhesion on
      periphyton samples (biological material coating submerged surfaces). The
      concentrations of 137Cs and stable Cs (133Cs) in periphyton, suspended particles
      and filtered water were measured to determine the net water-to-periphyton
      concentration ratios for 137Cs and stable Cs. The net amount of 133Cs (or 137Cs)
      taken up by periphyton was calculated by subtracting from the total amount of
      133Cs (or 137Cs) on the collected material (periphyton + inorganic particles),
      the 133Cs (or 137Cs) due to the inorganic particles adhering to periphyton. The
      mass of suspended particles adhering to the periphyton surface was calculated
      using scandium as an indicator of the mineral fraction of the suspended
      particles. The relationship between the concentration ratios for 137Cs and stable
      Cs and suspended particle adhesion on periphyton external surfaces is discussed.

PMID- 11954718
TI  - Assessment of prospective foodchain doses from radioactive discharges from BNFL
      Sellafield.
AB  - This paper presents the method used by the UK Food Standards Agency (FSA) to
      assess the potential impact of proposed radioactive discharges from the
      Sellafield nuclear site on food and determine their acceptability. It explains
      aspects of a cautious method that has been adopted to reflect the UK government
      policy and uncertainties related to people's habits with regard to food
      production and consumption. Two types of ingestion doses are considered in this
      method: 'possible' and 'probable' doses. The method is specifically applied to
      Sellafield discharge limits and calculated possible and probable ingestion doses
      are presented and discussed. Estimated critical group ingestion doses are below
      the dose limit and constraint set for members of the public. The method may be
      subject to future amendments to take account of changes in government policy and
      the outcome of a recent Consultative Exercise on Dose Assessments carried out by
      FSA. Uncertainties inherent in dose assessments are discussed and quantified
      wherever possible.

PMID- 11954719
TI  - Use of 129I and 137Cs in soils for the estimation of 131I deposition in Belarus
      as a result of the Chernobyl accident.
AB  - Using radioactivity measurements for 131I and 137Cs and nuclear activation
      analysis (NAA) or accelerator mass spectrometry (AMS) for 129I, ratios of
      131I/137Cs and 129I/137Cs have been determined in soils from Belarus. We find
      that the pre-Chernobyl ratio of 129I/137Cs in Belarus is significantly larger
      than expected from nuclear weapons fallout. For the Chernobyl accident, our
      results support the hypothesis that there was relatively little fractionation of
      iodine and caesium during migration and deposition of the radioactive cloud. For
      sites having 137Cs > 300 Bq/kg, 129I can potentially give more reliable
      retroactive estimates of Chernobyl 131I deposition. However, our results suggest
      that 137Cs can also give reasonably good (+/-50%) estimates for 131I in Belarus.

PMID- 11954720
TI  - Artificial radionuclides in sediments of the Don River Estuary and Azov Sea.
AB  - The Don River Estuary-Azov Sea system is an extension of the shallow continental
      shelf area of the Black Sea. A large data set of artificial radionuclides in
      bottom sediments of the Azov Sea has been compiled in order to examine the
      storage and migration of radionuclides within this highly restricted inland sea
      and to estimate the annual dose received by individuals in the local population
      who regularly consume fish. In recent years (1997-1999), the radionuclide content
      of surface sediments has been: 137Cs < or = 0.5-100 Bq/kg d.w. (mean = 33.8 +/-
      25.9 Bq/kg d.w., n = 57), 90Sr = 0.2-5.7 Bq/kg d.w. (mean = 2.1 +/- 1.4 Bq/kg
      d.w., n = 34) and 239,240Pu = 0.31-0.51 Bq/kg d.w. (n = 2). In general, 137Cs
      activities increase with distance from the mouth of the Don River and correlate
      negatively with sediment grain size (r2 = 0.77, n = 21). The annual 137Cs-derived
      dose received by an individual through the trophic chain water-fish-humans
      (approximately 10(-6) Sv/yr) is well below regulatory recommended limits,
      indicating that current levels of radioactivity in the environment pose no threat
      to commercial fisheries operations for the bordering nations of Russia and
      Ukraine.

PMID- 11954721
TI  - Incorporating soil structure and root distribution into plant uptake models for
      radionuclides: toward a more physically based transfer model.
AB  - Most biosphere and contamination assessment models are based on uniform soil
      conditions, since single coefficients are used to describe the transfer of
      contaminants to the plant. Indeed, physical and chemical characteristics and root
      distribution are highly variable in the soil profile. These parameters have to be
      considered in the formulation of a more realistic soil-plant transfer model for
      naturally structured soils. The impact of monolith soil structure (repacked and
      structured) on Zn and Mn uptake by wheat was studied in a controlled tracer
      application (dye and radioactive) experiment. We used Brilliant Blue and
      Sulforhodamine B to dye flow lines and 65Zn and 54Mn to trace soil distribution
      and plant uptake of surface-applied particle-reactive contaminants. Spatial
      variation of the soil water content during irrigation and plant growth informs
      indirectly about tracer and root location in the soil profile. In the structured
      monolith, a till pan at a depth of 30 cm limited vertical water flow and root
      penetration into deeper soil layers and restricted tracers to the upper third of
      the monolith. In the repacked monolith, roots were observed at all depths and
      fingering flow allowed for the fast appearance of all tracers in the outflow.
      These differences between the two monoliths are reflected by significantly higher
      54Mn and 65Zn uptake in wheat grown on the structured monolith. The higher uptake
      of Mn can be modelled on the basis of radionuclide and root distribution as a
      function of depth and using a combination of preferential flow and rooting. The
      considerably higher uptake of Zn requires transfer factors which account for
      variable biochemical uptake as a function of location.

PMID- 11954722
TI  - Transfer of 137Cs and stable Cs from paddy soil to polished rice in Aomori,
      Japan.
AB  - Rice is a staple food in Japan and other Asian countries, and the soil-to-plant
      transfer factor of 137Cs released into the environment is an important parameter
      for estimating the internal radiation dose from food ingestion. Soil and rice
      grain samples were collected from 20 paddy fields throughout Aomori Prefecture,
      Japan in 1996 and 1997, and soil-to-polished rice transfer factors were
      determined. The concentrations of 137Cs, derived from fallout depositions, stable
      Cs and K in paddy soils were 2.5-21 Bq kg(-1), 1.2-5.3 and 5000-13000 mg kg(-1),
      respectively. The ranges of 137Cs, stable Cs and K concentration in polished rice
      were 2.5-85 mBq kg(-1) dry wt., 0.0005-0.0065 and 580-910 mg kg(-1) dry wt.,
      respectively. The geometric mean of soil-to-polished rice transfer factor of
      137Cs was 0.0016, and its 95% confidence interval was 0.00021-0.012. The transfer
      factor of 137Cs was approximately 3 times higher than that of stable Cs at
      0.00056, and they were well correlated. This implied that fallout 137Cs, mostly
      deposited up to the 1980s, is more mobile and more easily absorbed by plants than
      stable Cs in the soil, although the soil-to-plant transfer of stable Cs can be
      used for predicting the long-term transfer of 137Cs. The transfer factors of both
      137Cs and stable Cs decreased with increasing K concentration in the soil. This
      suggests that K in the soil was a competitive factor for the transfers of both
      137Cs and stable Cs from soil-to-polished rice. However, the transfer factors of
      137Cs and stable Cs were independent of the amount of organic materials in soils.

PMID- 11954723
TI  - An integrated programme for municipal solid waste management.
AB  - A mathematical model is used in planning an integrated programme for the
      management of municipal solid waste to solve an economical optimisation problem
      and allow preliminary decisions to be made at the operational planning phase. The
      model, based on networks depicting the municipal solid waste management cycle, is
      simple to apply and furnishes easily assimilated results that facilitate
      management choices. Its application in an optimised area within the Regione
      Campania in Italy demonstrates how it may be used to evaluate the economic
      advantages pertaining to different municipal solid waste collection and treatment
      options.

PMID- 11954724
TI  - Integrated analysis for pre-sorting and waste collection schemes implemented in
      Spanish cities.
AB  - Over recent years, European cities have been questioning their traditional pre
      sorting and waste collection practices and looking for new schemes to improve
      environmental problems generated by waste disposal. This paper presents an
      integral methodology for four pre-sorting practices that are beginning to be
      implemented in Spanish cities. A great effort has been made to compile
      information to be able to estimate a large number of valuation indexes. Based on
      this information, the methodology is supported by the forecasting of waste
      generation, the use of GIS techniques, the definition of objectives and their
      evaluation taking into account legal, social, performance, environmental and
      economic issues. Special attention is given to environmental impact, for which
      life cycle assessment methodology is used.

PMID- 11954725
TI  - Evaluation of multifarious solid waste management systems--a goal programming
      approach.
AB  - Globally the waste management systems are becoming resource generative by
      incorporating energy and material recovery components in the systems. These
      systems are expected to meet several objectives and thus cannot be analysed
      effectively by optimising models using single objective like cost minimisation.
      To study the system's performance under varying priority structures of the
      conflicting objectives an interactive goal programming model of multi-objective
      planning of the system is proposed. The model is applied to visualise the system
      performance for a typical county region and accordingly its utility has been
      demonstrated. The application highlights the effect of change in priority
      structure on the extent of meeting the objectives. The proposed analytical tool
      facilitates the use of the model for tactical and strategical planning not only
      in developed countries like the UK but would provide better insight in developing
      energy and material recovery units in developing countries like India.

PMID- 11954726
TI  - The numerical modelling and process simulation for the fault diagnosis of rotary
      kiln incinerator.
AB  - The numerical modelling and process simulation for the fault diagnosis of rotary
      kiln incinerator were accomplished. In the numerical modelling, two models
      applied to the modelling within the kiln are the combustion chamber model
      including the mass and energy balance equations for two combustion chambers and
      3D thermal model. The combustion chamber model predicts temperature within the
      kiln, flue gas composition, flux and heat of combustion. Using the combustion
      chamber model and 3D thermal model, the production-rules for the process
      simulation can be obtained through interrelation analysis between control and
      operation variables. The process simulation of the kiln is operated with the
      production-rules for automatic operation. The process simulation aims to provide
      fundamental solutions to the problems in incineration process by introducing an
      online expert control system to provide an integrity in process control and
      management. Knowledge-based expert control systems use symbolic logic and
      heuristic rules to find solutions for various types of problems. It was
      implemented to be a hybrid intelligent expert control system by mutually
      connecting with the process control systems which has the capability of process
      diagnosis, analysis and control.

PMID- 11954727
TI  - Solid waste characterisation study in the Guadalajara Metropolitan Zone, Mexico.
AB  - The key findings of a solid waste characterisation study conducted at the
      Guadalajara Metropolitan Zone, Mexico, are reported. Objectives of the study were
      to estimate the daily generation rate of household (HSW) and municipal solid
      waste (MSW), characterise and compare their composition by type of material,
      determine the proportion that HSW contributes to MSW, explore changes in MSW
      composition through time after final disposal, and estimate the types and amount
      of MSW that are sorted out for recycling at final disposal sites. HSW generated
      during seven days by a sample of 300 households chosen through a two-stage
      stratified sampling design was collected, weighed and classified. MSW entering
      the four local disposal sites was recorded for 12 weeks, and materials' sorting
      was quantified. MSW samples taken by excavating trenches in two final disposal
      sites were also characterised. The average per capita daily HSW generation rate
      was 508 g. HSW mainly consisted of putrescible waste (53%), paper (10%) and
      plastic (9%). The average daily generation rate of MSW was 3119.2 metric tonnes.
      HSW represented 55.9% of MSW, and the main difference between HSW and MSW was a
      lower proportion of organic materials (53% vs. 16.5%, respectively). The major
      changes in MSW composition through time after final disposal, were the result of
      the quick decomposition of putrescible materials. Only 2.2% of total MSW
      generated in Guadalajara (mainly package waste) was sorted for recycling.

PMID- 11954728
TI  - Mathematical modelling of landfill gas migration in MSW sanitary landfills.
AB  - The laws that govern the displacement of landfill gas in a sanitary landfill are
      analysed. Subsequently, a 2-D finite difference flow model of a fluid in a steady
      state in a porous medium with infinite sources of landfill gas is proposed. The
      fact that landfill gas is continuously generated throughout the entire mass of
      the landfill differentiates this model from others extensively described in the
      literature and used in a variety of different applications, such as oil recovery,
      groundwater flow, etc. Preliminary results are then presented of the application
      of the model. Finally, the results obtained employing data from the literature
      and experimental assays carried out at the La Zoreda sanitary landfill (Asturias,
      Spain) are discussed and future lines of research are proposed.

PMID- 11954729
TI  - The influence of hydraulic residence time on the treatment of cattle manure in
      UASB reactors.
AB  - Cattle manure from farms in the autonomous community of Asturias, Spain, was
      characterised and subsequently treated, after filtration through a 1 mm sieve, in
      upflow anaerobic sludge blanket laboratory reactors. The volume generated per cow
      and day varied between 50-55 litres (obtained through a survey of 400 farms), the
      manure being used on Asturian farms up until now as a fertiliser. After
      screening, the COD of the manure employed varied between 33,000 and 56,000 mgO2
      l(-1). The highest percentage of COD removal obtained was 75.5% for a hydraulic
      residence time of 22.5 days. Gas production varied between values of 0.20-0.39
      m3gas kg(-1) COD removed, with a methane content of up to 64%. There was a
      fraction refractory to biodegradation of 11%.

PMID- 11954730
TI  - Toxicity and hazardous properties of solvent base adhesive wastes.
AB  - In this work, the hazardous properties of solvent base adhesive wastes generated
      in the footwear manufacturing process have been studied. The characterisation
      procedures and criteria used are those contained in the legal documents European
      Union Council Decision 94/904/CE and October 13th Spanish Ministerial Order. The
      properties studied were the following: flash point, reactivity (gas generation),
      ecotoxicity, main contaminants extracted by the leaching process and main harmful
      substances contained in wastes. An additional study of the relationship between
      flash point and solvent concentration in waste was carried out for polyurethane
      acetone and neoprene-toluene systems. The wastes considered were metal containers
      with remains of dry or semi-dry adhesive. The results obtained show that the
      presence of solvent in wastes confers on them hazardous characteristics (flash
      point and harmful composition) depending on the solvent type and its
      concentration.

PMID- 11954731
TI  - Economic considerations of chromium recovery from tanning wastewater.
AB  - The chrome recovery from tanning wastewater was investigated in field conditions
      using a real-sized pilot plant. The tested wastewaters were from the tanning
      process both without and with tanning additives, whereas the precipitating
      chemicals of interest were magnesium oxide (MgO) and sodium carbonate (Na2CO3).
      The precipitation with MgO followed by 1 hour sedimentation was the best
      solution. The optimal dosages were 2 and 4 times that of stoichiometric
      requirements for conditions without and with the additives, respectively. By
      redissolving the obtained sludge with 1:1 diluted sulfuric acid and maintaining
      the pH between 2.5 and 2.8, the chromium recovery were 97.6 and 88.6%,
      respectively. Another alternative of using Na2CO3 as the precipitant was not
      promising because of its high chemical cost and excessive sludge-settling period
      (15-20 hours). The MgO precipitation scenario proved to be able to pay back
      economically within 3 years for the "without-additive" waste stream whereas that
      of "with-additive" wastewater was not worth the investment. This is because the
      "with-additive" discharge contains low chromium content whereas it requires high
      chemical doses.

PMID- 11954732
TI  - Compressive strength and heavy metal leaching behaviour of mortars containing
      spent catalyst.
AB  - This investigation was set and aimed to study the possibility of using spent
      catalyst as a concrete constituent which the spent catalyst was used as sand.
      Besides the spent catalyst was used as sand, it was also ground to very small
      particle size as small as that of cement and used as 20% replacement of cement by
      weight. Compressive strengths and leaching characteristics of lead, chromium,
      cadmium, and nickel in mortars containing spent catalyst and ground spent
      catalyst were tested. The results presented revealed that the compressive
      strength of mortar containing spent catalyst increased with ages. The results
      also indicated that the compressive strength of mortar containing spent catalyst
      at the proportion of 1.25 times of cement by weight was strong enough to make a
      concrete brick. In case of the ground spent catalyst being used to replace
      cement, it made the compressive strength lower than that of the standard mortar
      approximately 20%. The leachate results of lead and chromium from spent catalyst
      were lower than the allowance, but cadmium and nickel exceeded the limits. After
      the spent catalyst was fixed with cement, the leaching of the heavy metals did
      not exceed the industrial effluent standard. Therefore, the heavy metals
      mentioned earlier were not a problem in using spent catalyst as a concrete
      constituent.

PMID- 11954733
TI  - Red mud of aluminium production waste as basic component of new construction
      materials.
AB  - The work presented here shows the possibility of using the red mud waste from the
      Bayer process used for aluminium production as the main component of new
      construction materials. It describes some recent experiments lasting 180 days as
      well as some 1 year old samples. The best part of materials used are industrial
      wastes, but some of them contain small (no more the 2%) additions of CaO or
      Portland Cement (PC) to increase the strengthening rate of the samples. The high
      strength values of these materials allow their use as new materials for road and
      airfields bases, levee core, dumps, foundations, etc. They can also be used to
      make bricks, tiles, and similar items. In addition to the economic factors, these
      materials are very easy to use and no new residues are generated. The results of
      the heavy metal leaching tests, not included in this paper, show very low levels
      of their leachability in acid solutions, far below the demands of the Spanish
      environmental standards. This can be explained by the strong chemical binding of
      heavy metals in practically insoluble chemical compositions.

PMID- 11954734
TI  - Key(s) to marine ecology and understanding pollution impacts--a tribute to Dr.
      Howard Sanders, marine benthic biologist extra-ordinaire.

PMID- 11954735
TI  - The acute and chronic effects of wastes associated with offshore oil and gas
      production on temperate and tropical marine ecological processes.
AB  - A review of the acute and chronic effects of produced formation water (PFW),
      drilling fluids (muds) including oil-based cutting muds, water-based cutting
      muds, ester-based cutting muds and chemical additives, and crude oils associated
      with offshore oil and gas production was undertaken in relation to both temperate
      and tropical marine ecological processes. The main environmental effects are
      summarized, often in tabular form. Generally, the temporal and spatial scales of
      these studies, along with the large levels of inherent variation in natural
      environments, have precluded our ability to predict the potential long-term
      environmental impacts of the offshore oil and gas production industry. A series
      of critical questions regarding the environmental effects of the offshore oil and
      gas production industry that still remain unanswered are provided for future
      consideration.

PMID- 11954736
TI  - Using genetic techniques to investigate the sources of the invasive alga Caulerpa
      taxifolia in three new locations in Australia.
AB  - The invasive green alga Caulerpa taxifolia has gained a high profile due to
      'outbreaks' in the Mediterranean and California. During the year 2000 three new
      discrete locations colonised by abundant C. taxifolia were discovered in New
      South Wales (NSW), Australia. Sequencing of the internal transcribed spacer (ITS)
      region of the ribosomal DNA was used to explore the source(s) of these new
      records, which is an important prerequisite for subsequent environmental
      management responses. Our results indicate that the NSW C. taxifolia originated
      from several sources and, hence, through different invasion events. For two of
      the new records (Port Hacking, Careel Bay) it can be excluded that they are
      derived from the so-called "aquarium strain" of C. taxifolia, closely related to
      the invasive Mediterranean populations. Port Hacking is likely to have originated
      from tropical native populations. However, samples from Lake Conjola cannot be
      sufficiently distinguished with the applied technique from native C. taxifolia in
      Moreton Bay and the Mediterranean/"aquarium strain".

PMID- 11954737
TI  - Marine debris ingestion in loggerhead sea turtles, Caretta caretta, from the
      Western Mediterranean.
AB  - Marine debris represents an important threat for sea turtles, but information on
      this topic is scarce in some areas, such as the Mediterranean sea. This paper
      quantifies marine debris ingestion in 54 juvenile loggerhead sea turtles (Caretta
      caretta) illegally captured by fishermen in Spanish Mediterranean waters. Curved
      carapace length was measured, necropsies were performed and debris abundance and
      type was recorded. Different types of debris appeared in the gastrointestinal
      tract of 43 turtles (79.6%), being plastics the most frequent (75.9%). Tar,
      paper, Styrofoam, wood, reed, feathers, hooks, lines, and net fragments were also
      present. A regression analysis showed that the volume of debris increased
      proportionally to the size of the turtles. The high variety of debris found and
      the large differences in ingestion among turtles indicated low feeding
      discrimination of this species that makes it specially prone to debris ingestion.
      Our data suggest that more severe control of litter spills and greater promotion
      of environmental educational programmes are needed in the Western Mediterranean.

PMID- 11954738
TI  - Trace metals in tissues of gray whale (Eschrichtius robustus) carcasses from the
      Northern Pacific Mexican Coast.
AB  - Samples of liver, lung, heart, muscle, and blubber tissue from the carcasses of
      juvenile gray whales (Eschrichtius robustus) found stranded on the coast off the
      Sea of Cortez, Mexico were analyzed for a range of trace metals (Cu, Fe, Zn, Mn,
      Ni, Pb, and Cd). The highest concentrations of copper, iron, zinc, and manganese
      were found in liver; nickel and lead in heart, and cadmium in kidney. In all
      tissues analyzed, iron, zinc and copper were present in the highest
      concentrations; however, some whales also showed high levels of cadmium in the
      kidney which could be related to their diet. Elevated concentrations of copper
      were found only in the liver of one whale. In general, where low levels of iron
      were found in the liver, they were associated with poor nutrition. Lead, nickel,
      manganese and zinc levels in liver were within the normal range, indicating that
      these whales had not been exposed to high levels of these metals.

PMID- 11954739
TI  - Measurement of environmental trace-metal levels with transplanted mussels and
      diffusive gradients in thin films (DGT): a comparison of techniques.
AB  - Transplanted mussels and diffusive gradients in thin films (DGT) were used to
      assess levels of cadmium, copper, lead and zinc at four sites situated inside and
      outside of two enclosed marinas, near Melbourne, Australia. Mussels accumulated
      all metals except cadmium. Over one year, there were large temporal differences
      in tissue metal levels in mussels, but differences between sites were only
      apparent for copper and lead. DGT showed temporal differences of the same kind as
      those seen in the mussels, but appeared to have more power to discriminate
      between sites. DGT found higher copper levels inside marinas than outside, and
      high levels of zinc were found inside one marina. Levels of copper and zinc were
      high enough to be of environmental concern for one site. The effect of fouling on
      DGT measurements will have to be quantified, or avoided by the use of multiple
      short-term exposures, if the technique is to become a widespread in situ
      monitoring tool.

PMID- 11954740
TI  - EROD activity, serum SDH and PAH biliary metabolites in sand flathead
      (Platycephalus bassensis) collected in Port Phillip Bay, Australia.
AB  - In order to evaluate the health status of fish inhabiting Port Phillip Bay,
      Australia, southern sand flathead (Platycephalus hassensis, N = 133) were
      collected at six stations throughout the Bay. Fish had a similar serum sorbitol
      dehydrogenase (SDH) activity level (p = 0.12), indicating that they were not
      experiencing hepatocellular injuries. Ethoxyresorufin-O-deethylase (EROD)
      activity was generally lower in the non-urbanized and non-industrialized southern
      part of the Bay. The highest EROD activity was observed in Hobson Bay, the
      closest station from Melbourne city. Naphthalene-type biliary metabolites were
      also highest in Hobson Bay with intermediate levels found in Corio Bay where
      refineries are present. An opposite trend was observed with the pyrene-type bile
      metabolites, the highest levels being observed in Corio Bay while intermediate
      levels were found in Hobson Bay. The ratio of naphthalene-type to benzo(a)pyrene
      (B(a)P)-type metabolites indicate that relatively to other sites sampled in Port
      Phillip Bay, Corio Bay is subjected to enriched petroleum hydrocarbons of
      pyrolytic origin. Temporal trends indicate that the availability of xenobiotics
      to fish remained unchanged over the 1990s.

PMID- 11954741
TI  - Evaluating the genotoxic damage and hepatic tissue alterations in demersal fish
      species: a case study in the Ligurian Sea (NW-Mediterranean).
AB  - A protocol for detecting hepatic micronuclei in fish was performed to check
      genotoxic damage, as an indicator of environmental hydrocarbons exposure, in
      relation to the "Haven" oil spill. As target fish, we have chosen three demersal
      species with different habitats and feeding behaviour (i.e., Lepidorhombus
      boscii, Merluccius merluccius and Mullus barbatus) collected from two differently
      impacted areas and a control site. Additional analysis was performed by
      histological detection of hepatic tissue damages such as the presence of necrotic
      and tumour-like aspects. The three studied species showed different sensitivity
      to environmental pollutants exposure, L. boscii resulting the more sensitive in
      terms of both micronuclei incidence and tissue damage. The results of this study
      show that: (1) the micronucleus test could be an effective and fast method to
      detect oil pollution; (2) a clear response of L. boscii only to oil contamination
      for both micronucleus test and liver tissue alterations.

PMID- 11954742
TI  - Leaf biochemical parameters in Avicennia marina (Forsk.) Vierh as potential
      biomarkers of heavy metal stress in estuarine ecosystems.
AB  - Sediment loadings and leaf accumulation of the heavy metals copper (Cu), lead
      (Pb) and zinc (Zn) with accompanying changes in leaf chlorophylls' (a + b),
      carotenoids and the antioxidant enzyme peroxidase were examined in the grey
      mangrove Avicennia marina (Forsk.) Vierh, in order to determine the applicability
      of these parameters as biomarkers of heavy metal stress under field conditions.
      Copper was found to show limited accumulation to leaf tissue, following a linear
      relationship at lower sediment concentrations, with saturation at higher sediment
      Cu concentrations. Copper accumulation relationships to leaf tissue were
      maintained temporally, and increases in sediment Cu, salinity, and decreases in
      sediment pH and Zn contributed to the accumulation of Cu to leaf tissue. Lead
      showed a significant relationship between sediment and leaf Pb levels, but
      accumulation was minimal. Accumulation relationships for Pb were not maintained
      temporally, and high sediment Pb, low pH and organic content increased
      bioavailability and accumulation of Pb. Zinc was the most mobile of all metals
      and was accumulated to the greatest quantities in leaf tissue in a dose-dependant
      relationship. Some temporal variation in Zn accumulation occurred, and higher
      sediment pH, organic content Zn and Pb promoted leaf Zn accumulation. Leaf Cu and
      Zn showed the strongest relationship with peroxidase activity and to a lesser
      degree Pb. Zinc was the only accumulated metal to show relationship maintenance
      with peroxidase activity over time. It was found that peroxidase activity best
      reflects the total phytotoxic effect from the combined metal stress of all three
      accumulated leaf metals. The only significant photopigment relationship evidenced
      was that of leaf Zn with the chlorophyll a/b ratio, but was not maintained
      temporally. Peroxidase activity may be an appropriate biomarker for Zn or total
      metal accumulation in leaf tissue, and the chlorophyll a/b ratio a suitable
      biomarker of Zn accumulation though requires temporal monitoring under field
      conditions.

PMID- 11954743
TI  - Further recovery of northeast Pacific neogastropods from imposex related to
      tributyltin contamination.

PMID- 11954744
TI  - Serum hepatocyte growth factor combined with vascular endothelial growth factor
      as a predictive indicator for the occurrence of coronary artery lesions in
      Kawasaki disease.
AB  - We investigated the possible use of serum hepatocyte growth factor (HGF) and
      vascular endothelial growth factor (VEGF) levels as a predictive indicator for
      the occurrence of coronary artery lesions (CAL) in Kawasaki disease (KD). Serum
      HGF and VEGF levels were measured by enzyme-linked immunosorbent assay in 41
      patients with KD and 25 afebrile controls. Serum HGF levels of patients in the
      acute phase of KD were significantly higher than those of afebrile controls (Pc <
      0.05) and decreased to lower levels during recovery (P < 0.0001). Univariate
      analysis showed significant correlations between occurrence of CAL and five
      variables: duration of fever (P=0.018), serum C-reactive protein concentration (P
      = 0.024), albumin concentration (P=0.009). serum VEGF level (P=0.009) and serum
      HGF level (P=0.035). Furthermore, multivariate analysis revealed that serum HGF
      and VEGF levels and presence of oedema were major risk factors for the occurrence
      of CAL. For prediction of the development of CAL, we established a new risk
      classification system with these three variables, which showed a sensitivity of
      100% and a specificity of 94.4%. CONCLUSION: these data show that hepatocyte
      growth factor, together with vascular endothelial growth factor, might play an
      important role in the pathophysiology of Kawasaki disease and their serum levels
      could be a powerful predictor for the development of coronary artery lesions.

PMID- 11954745
TI  - The first case of the FRAXE form of inherited mental retardation in Croatia.

PMID- 11954746
TI  - Pepper syndrome, truncus arteriosus communis and abnormal pulmonary venous
      return: an unusual association.

PMID- 11954747
TI  - Ventricular septal defect and deletion of chromosome 22q11: anatomical types and
      aortic arch anomalies.

PMID- 11954749
TI  - Recurrent herpetic whitlow in an immune competent girl without vesicular lesions.

PMID- 11954748
TI  - Eosinophilic fasciitis successfully treated with oral hydroxyzine: a new
      therapeutic use of an old drug?

PMID- 11954750
TI  - Impact of pneumococcal vaccination in Senegalese HIV-1-infected children.

PMID- 11954751
TI  - Presymptomatic diagnosis of Wilson disease associated with a novel mutation of
      the ATP7B gene.

PMID- 11954752
TI  - A child presenting with disordered consciousness, hallucinations, screaming
      episodes and abdominal pain.

PMID- 11954753
TI  - Umbilical artery catheters: more dangerous than useful?

PMID- 11954754
TI  - Low molecular weight heparin in children.
AB  - Low molecular weight heparins potentially have significant advantages over
      unfractionated heparin and oral anticoagulants for both the prevention and
      treatment of thromboembolic events in children. Compared to standard heparin, low
      molecular weight heparins have superior bioavailability, a longer half-life, and
      a dose-independent clearance, which results in a more predictable anticoagulant
      response. Low molecular weight heparins are administered subcutaneously and
      require minimal laboratory monitoring and dose adjustment, offering important
      benefits to children with poor venous access. In addition, complications
      including osteoporosis and heparin-induced thrombocytopenia are relatively rare
      with low molecular weight heparins compared to unfractionated heparin.
      CONCLUSION: based on the available data, low molecular weight heparins seem to be
      an efficient and safe alternative to standard anticoagulation therapy with
      unfractionated heparin and oral anticoagulants for both treatment and prevention
      of thromboembolic events in children of varying ages and underlying disorders.

PMID- 11954755
TI  - Unilateral CHARGE association.
AB  - A case with a predominantly unilateral CHARGE association is reported. The CHARGE
      association refers to a combination of congenital malformations. This boy had
      left-sided anomalies consisting of choanal atresia, coloboma and peripheral
      facial palsy. The infant had a frontal encephalocele, an anomaly not included in
      the definitions of CHARGE association. CONCLUSION: even when anomalies are
      predominantly unilateral, the CHARGE association should be considered in the
      differential diagnosis.

PMID- 11954756
TI  - A girl with bilateral ovarian tumours: Frasier syndrome.
AB  - Frasier syndrome (FS) is characterised by male pseudohermaphroditism, slowly
      progressing nephropathy and frequent development of gonadoblastoma. The Wilms'
      tumour suppressor gene (WT1 gene) plays an important role in the development of
      the urogenital system and the gonads. A splice mutation in intron 9 of the WT1
      gene was recently described in patients with FS. We analysed the WT1 gene of a
      Japanese patient with male pseudohermaphroditism, steroid resistant-nephr-opathy
      and gonadoblastoma by the polymerase chain reaction and direct sequencing and
      detected a heterozygous point mutation in intron 9. CONCLUSION: analysis of the
      Wilms' tumour suppressor gene in a patient with Frasier syndrome by the
      polymerase chain reaction and direct sequencing detected a + 5G -->A transition
      at a position of the second alternative splice region of exon 9, important for
      predicting the risk of the occurrence of Wilms' tumour.

PMID- 11954757
TI  - Severe hypoalbuminaemia in a systemic lupus erythematosus-like patient.
AB  - Diffuse oedema due to hypoalbuminaemia is a common manifestation in patients
      affected with systemic lupus erythematosus. Hypoalbuminaemia is usually secondary
      to an ongoing glomerulonephritis leading to proteinuria or, more rarely, to
      decreased protein synthesis or deficient protein intake. Here, we report the case
      of a 6-year-old girl with a previous history of Evans' syndrome and mesangial
      glomerulonephritis who subsequently developed severe anasarca without apparent
      proteinuria. Faecal oal-antitrypsin showed a persistent severe intestinal protein
      loss (ranging from 1500 to 6.500 yl/g humid faeces, normal value < 200),
      consistent with the diagnosis of protein-losing enteropathy. An echographic
      examination of the abdomen revealed a diffuse thickening of the intestinal wall,
      particularly at the level of the small bowel, with an almost exclusive
      involvement of the submucosal layer. Colonoscopy revealed the presence of diffuse
      purpuric lesions at the level of the submucosa. Aggressive immunosuppressive
      treatment completely resolved the clinical picture. CONCLUSION: protein-losing
      enteropathy is an uncommon cause of hypoalbuminaemia during the course of
      systemic lupus erythrematosus. It may be considered as a clinical syndrome
      related to many pathological conditions leading to an excessive intestinal
      protein loss. Some conditions are related with an altered mucosal permeability,
      others with primary or secondary intestinal lymphangiectasia. A review of the
      possible causes of systemic lupus erythrematosus-associated protein-losing
      enteropathy reported in the paediatric literature is given.

PMID- 11954758
TI  - Neutrophil adherence receptor deficiency regressing with granulocyte-colony
      stimulating factor therapy in a case of glycogen storage disease type Ib.
AB  - Neutrophils from patients suffering from glycogen storage disease type Ib (GSD
      Ib) show marked functional deficiencies (chemotaxis, respiratory burst, and
      phagocytosis). Here we describe neutrophil adherence receptor (L-selectin CD62L
      and beta2 integrins CD11b/CD18) deficiency in a patient with genotype of GSD-Ib,
      who presented with recurrent infections, diminished neutrophil count and impaired
      functions. Treatment with granulocyte-colony stimulating factor (G-CSF) had a
      beneficial effect on the infectious status, the enhancement of phagocytosis and
      the regression of the adherence receptor defect. CONCLUSION: this is the first
      observation of a patient with glycogen storage disease type Ib with a deficiency
      in leucocyte adherence receptor expression, which regressed with growth factor
      therapy. It underlines the potential role of these receptors in the genesis of
      recurrent infections which occur in patients with this disease.

PMID- 11954759
TI  - High density lipoprotein-cholesterol changes in children with high cholesterol
      levels at birth.
AB  - The predictive value of serum lipoprotein concentrations at birth for the same
      parameters later in life is under debate. A group of 20 children displaying high
      total cholesterol (TC) levels at birth (group 2) were compared at age 4 years
      with 18 control children who had presented a normal lipoprotein profile at birth
      (group 1). There was a significant correlation between TC, low density
      lipoprotein-cholesterol, high density lipoprotein (HDL)-cholesterol, and
      apolipoprotein (Apo) A-I levels at age 4 years and at birth. The increases in TC
      and HDL-cholesterol levels from birth to age 4 years were significantly lower (P
      < 0.05, P < 0.01, respectively) in group 2 than in the control group and
      inversely correlated with the concentrations of these parameters at birth. The
      increases in HDL-cholesterol and Apo A-I levels were higher in males while those
      of triacylglycerol and Apo B were higher in females (P < 0.05). However, the
      increases in TC and HDL-cholesterol were higher in controls (P< 0.05). Diets of
      children of both groups were similar regarding the energy contribution of
      saturated, monounsaturated and polyunsaturated fatty acids, although children
      from group 2 ate less fish and omega-3 fatty acids (P < 0.05). CONCLUSION: the
      present data suggest for the first time that when high density lipoprotein
      cholesterol levels are high at birth, those levels increase less during the first
      four years of life. Moreover, low density lipoprotein-cholesterol increased about
      five times as much as high density lipoprotein-cholesterol did in controls and
      about 15 times as much as in the children with high cholesterol at birth.

PMID- 11954760
TI  - Unilateral decompressive craniectomy for children with severe brain injury.
      Report of seven cases and review of the relevant literature.
AB  - Severe head injuries in children (under 15 years of age) have many features that
      differentiate them from head injuries in adults. In such cases, non-surgical
      treatment cannot always prevent fatal herniation. We report on seven cases of
      children with severe head injury, presenting with decorticate posturing and
      treated by unilateral decompressive craniectomy. The aim of the unilateral
      decompressive craniectomy was to decompress the midbrain and the brainstem. Post
      operatively, all patients showed good recovery within 5 weeks (Glasgow Coma Scale
      score 15). The alternative treatment modalities are discussed critically in an
      attempt to determine the value of the unilateral decompressive craniectomy
      procedure and to define the clinical parameters that might identify those
      children most likely to benefit from this technique. CONCLUSION: the unilateral
      decompressive craniectomy has an advantage over non-surgical treatment of
      children with severe brain injury and should be considered in their management.

PMID- 11954761
TI  - Cerebral cavernomas in the adult. Review of the literature and analysis of 72
      surgically treated patients.
AB  - The authors review the pertinent literature dealing with all aspects of cerebral
      cavernous malformations in the adult. Clinical, neuroradiological, pathological,
      and epidemiological aspects are presented. The clinical significance of bleeding
      from cavernous malformations and various hemorrhage patterns are discussed in
      relation to the factors that influence hemorrhage rates. Recent reports
      describing the genetic mechanisms of inheritance, de novo formation, and
      angiogenesis of cavernomas are reviewed as well. Brainstem cavernomas have
      received special attention, since their clinical management is controversial in
      the literature. Presently, microsurgical removal is favored by the majority of
      authors and stereotactic radiosurgery appears to be inappropriate for prevention
      of bleeding from a cavernoma. Our own case material consists of data of 72
      patients operated upon during the past 5 years. Twenty-four patients harbored the
      lesion within the brainstem, 18 within the deep white matter of the hemispheres,
      12 in the basal ganglia or thalamus, 11 in superficial areas of the hemisphere,
      and seven within the cerebellum. The perioperative morbidity rate was 29.2%
      (21/72) while the rate of long-term morbidity was 5.5% (4/72), with no mortality
      in this series. It is concluded that cerebral cavernous malformations, including
      lesions in critical regions of the brain, can be treated microsurgically with
      excellent results and an acceptable morbidity.

PMID- 11954762
TI  - Cyst of the medullary conus: malformative persistence of terminal ventricle or
      compressive dilatation?
AB  - The ventriculus terminalis is a cavity situated at the level of the conus
      medullaris, enclosed by ependymal tissue and normally present as a virtual cavity
      or as a mere ependymal residue. In rare cases, and almost exclusively in
      pediatric age, the ventriculus terminalis may be visualized by radiological
      investigations, either by sonography or MRI, and represents a transient finding
      in children under 5 years of age. In pathological conditions, a cyst of the conus
      medullaris is probably the result of a persistent ventriculus terminalis and is
      usually described in children in association with a tethered cord; in a very
      limited number of cases, it has been described in adults whose clinical symptoms
      consist of neurological and/or sphincter disturbances not associated with other
      pathologies. The authors describe the case of a 42-year-old female with a cyst of
      the conus whose only symptom was imperious minction; she had been suffering from
      these urinary disorders for many years. The patient was not operated on because
      the clinical situation remained stable, without modifications of the MRI in
      follow-up over a 6-year period. The authors therefore suggest that in adult
      patients, a cyst of the conus medullaris is probably an expression of
      malformative persistence of the fifth ventricle and does not necessarily have a
      progressive evolution.

PMID- 11954763
TI  - Cerebellar hemangioblastoma simulating arachnoid cyst on imaging and surgery.
AB  - A case of posterior fossa hemangioblastoma simulating arachnoid cyst on imaging
      and peroperatively is presented. In vivo proton MR spectroscopy showed evidence
      of large lactate and resonance at 2.37 ppm not observed earlier in the cystic
      lesions, including arachnoid cyst. The demonstration of this resonance may help
      in characterization of these lesions that may be confused with arachnoid cysts on
      imaging and during surgery.

PMID- 11954764
TI  - Intraspinal migration of a Kirschner wire 3 months after clavicular fracture
      fixation.
AB  - The authors describe a patient who had Kirschner (K-) wire osteosynthesis of a
      right lateral clavicular fracture and developed a tetraparesis after 3 months.
      Plain X-ray and CT scan showed an intraspinal migration of one K-wire through the
      intervertebral foramen of C5/6. The K-wire was pulled out through an opening of
      the wound over the right clavicle. No CSF fistula was seen. The patient recovered
      without any postoperative neurological deficit. Patients with K-wire
      osteosynthesis should be informed about the risk of dislocation and wandering and
      should regularly be seen in the outpatient clinic. Regular X-rays should be
      performed. The K-wires must be sufficiently bent at the distal end to prevent
      wandering into the proximal direction. The K-wires should be removed soon after 6
      weeks and, in cases of dislocation and migration, as early as possible.

PMID- 11954765
TI  - Brain metastasis of Merkel cell carcinoma.

PMID- 11954766
TI  - Cavernomas of the skull: review of the literature 1975-2000.
AB  - We describe four patients with intraosseous cavernous hemangiomas of the skull
      which were localized supraorbitally, parietally (two cases), and occipitally. The
      diameter ranged from 15 mm to 25 mm. They presented with slowly growing mass,
      tender to pressure, with spontaneous pain, and with freely mobile skin above the
      cavernoma sites. Magnetic resonance imaging (hyperintensity on T2 and
      isointensity with brain on T1) and CT (osteolytic lesion with erosion of the
      tabula externa) confirmed the plain skull films showing the honeycomb or sunburst
      appearance pattern. Resections and postoperative course were uneventful. In three
      of these cases there was coexistence with tumors (meningeoma, malignant lymphoma,
      and malignant melanoma); none of these constellations has been described before.
      Generally, cavernous hemangiomas of the skull are rare. There is one extensive
      review published by Barnes in 1984 regarding a period of 136 years with 123
      intraosseous hemangiomas of the skull and 74 of the jaws. Unfortunately, the
      histological confirmation is not completely clear and some capillary hemangiomas
      are included. In a review of the literature since 1975, we found 103
      histologically proven intraosseous cavernous hemangiomas of the skull (with our
      four cases included) and 22 of the jaws, which are shown in an overview with
      respect to their localization. The most frequent site was frontal, followed by
      temporal.

PMID- 11954767
TI  - Cavernous hemangioma of the temporal muscle.
AB  - Intramuscular cavernous hemangiomas are often found in the brain, but they are
      uncommon in the muscles of the head and neck region, with the masseter being the
      most frequent, followed by the trapezius and sternocleidomastoideus. Such a
      lesion in the temporal muscle is an extremely unusual situation. A 55-year-old
      man presented with intermittent headaches and painless swelling of the right
      temple region brought on by stress and bending forward. On MRI, T1-weighted
      imaging with enhancement after contrast medium showed a low signal-intense, fat
      free lesion restricted to the temporal muscle. T2 weighting showed a
      hyperintense, high fluid content, low-flow lesion. There was no progression
      within 2 years. No resection was performed. In planning a treatment approach, one
      must bear in mind that cavernous hemangiomas in the temporal muscle or other
      muscles of the head and neck can be clinically distinguished from the more
      aggressive capillary ones. Complications are extremely rare (hemorrhage or
      functional deficits). These cavernomas should simply be followed up and only
      resected in case of any problems (cosmetic, neurological deficits).

PMID- 11954768
TI  - Anatomical landmarks for image registration in frameless stereotactic
      neuronavigation.
AB  - OBJECTIVE: Frameless stereotactic navigation devices require preoperative
      application of skin markers (SM) and planning radiography, which limits their
      even wider use. Therefore, we prospectively studied the applicability and
      accuracy of anatomic "natural" markers (NM) for image registration. METHODS: The
      accuracy of NM was evaluated in 26 patients operated on in the supine (n=24) or
      sitting (n=2) position, either by comparison to our standard navigation protocol
      using SM and planning radiography or by the deviation of anatomic landmarks using
      a routine diagnostic radiograph. In 21 cases, NM were compared to SM with
      planning radiography (computed tomography, or CT, in nine cases and magnetic
      resonance imaging, or MRI, in 12). The root mean square error (RMSE) of the
      registered volume was calculated by the Philips EasyGuide Neuro frameless
      stereotactic navigation system and compared between the two registration
      modalities. RESULTS: The mean RMSE was 3.2 mm+/-1.0 mm standard deviation using
      NM vs 2.9+/-1.0 mm using self-adhesive SM (P=0.13, Student's t-test). Computed
      tomography was slightly more accurate than MRI planning (mean RMSE 3.2 mm vs 3.3
      mm). In three cases, diagnostic radiography (MRI) was used with a mean RMSE of
      5.3 mm but acceptable intraoperative landmark correlation. CONCLUSION: Our pilot
      study demonstrates insignificant loss of registration accuracy using NM compared
      to SM. Additionally, the radiologic planning investigation and accuracy loss due
      to SM movement may be avoided.

PMID- 11954769
TI  - Practicability of magnetoencephalography-guided neuronavigation.
AB  - Magnetoencephalography (MEG) is a noninvasive option for localizing
      electroneurophysiological activity on the human cortex. The purpose of this study
      was to evaluate the practicability and reliability of MEG imaging integrated into
      a neuronavigation system to identify the sensorimotor cortex intraoperatively in
      patients with brain tumors in or near the central motor strip. It was performed
      prior to surgery in 30 patients with space-occupying lesions in or around the
      central region to localize the primary somatosensory cortex. These functional
      brain maps were superimposed on MR images obtained prior to surgery and
      transferred in the operating room for intraoperative functional neuronavigation.
      During surgery, the phase reversal technique identified a generator which
      coincided with the somatosensory cortex as displayed by the MEG-based functional
      neuronavigation system. Following surgery, the motor deficit improved in seven
      patients, was unchanged in five, and showed a slight transient deterioration in
      five. One patient suffered a deterioration of motor function with incomplete
      recovery. The MEG-based functional neuronavigation was found to be practicable
      and useful in finding a safe approach to tumors in or adjacent to the central
      region. The accuracy of MEG was concluded to be reliable as verified by the phase
      reversal technique.

PMID- 11954770
TI  - Postmortem inspection for neurosurgery: a training model for endoscopic
      dissection technique.
AB  - In 63 specimens, 74 aneurysms, and five other lesions, postmortem microsurgical
      and endoscopic inspection (PMI) was done. This work not only allowed for safe
      pathoanatomic findings, but moreover showed characteristics of a training method
      developed according to a model with clear standards. PMI gives training in: 1.
      Understanding of pathoanatomic topography and syntopy. 2. Analysis of imaging
      findings. 3. Analysis of approaches (approach planning). 4. Paraendoscopic
      methods (video surgery). 5. Clipping training. 6. Analyzing the ergonomy of the
      setting and instrumentation. In the series presented, aneurysms were the focus of
      attention. Postmortem inspection trains nearly all manipulative and cognitive
      abilities necessary for operative management of this difficult lesion. The
      acceptance and applicability of this method for resident training must be
      evaluated in the future.

PMID- 11954771
TI  - Complications of burr-hole craniostomy and closed-system drainage for chronic
      subdural hematomas: a retrospective analysis of 376 patients.
AB  - OBJECTIVE: Burr-hole craniostomy with closed-system drainage (BCD) is the most
      frequently used neurosurgical treatment of chronic subdural hematomas (cSDH). The
      surgical and medical complications of BCD have seldom been investigated
      systematically. The objective of this study was to define the frequency of
      surgical and medical complications following BCD for cSDH. METHODS: The medical
      records of 376 patients managed by BCD were reviewed with respect to
      complications during the hospital stay. RESULTS: Seventy-seven surgical
      complications (20.5%) were encountered. The most frequent minor complication
      after surgery was seizures (n 51, 13.6%). The most frequent major surgical
      complications were intracerebral hemorrhage and subdural empyema (n 8, 2.1%
      each). Four patients with intracerebral hemorrhage died, accounting for a
      surgical mortality rate of 1.1%. Fifty-nine medical complications (15.7%)
      occurred during the hospital stay. Pneumonia was the most frequent medical
      complication (n 29, 7.7%). Medical complications were fatal in 24 patients,
      accounting for a mortality rate of 6.4%. In 22 patients (5.8%), death was not
      related to a complication, but to the initial brain damage. The overall mortality
      rate was 13.3%. CONCLUSION: The rate of complications in patients with cSDH who
      underwent the BCD is high. The clinical relevance of medical complications has to
      be emphasized because of their substantial contribution to overall mortality.

PMID- 11954772
TI  - Neuroprotective effects of propofol following global cerebral ischemia in rats.
AB  - Propofol has cerebral vascular and metabolic effects similar to those of
      barbiturates, and it is used to maintain neurosurgical anesthesia because it
      reduces cerebral metabolic rate, cerebral blood flow, and intracranial pressure.
      Although the use of propofol as a cerebral protectant during certain
      neurosurgical procedures has been advocated, consensus has not been reached as to
      a protective effect of propofol on cerebral ischemia. In this study we observed
      the neuroprotective effects of propofol during global cerebral ischemia
      reperfusion injury by the use of four-vessel occlusion method in a rat model. We
      measured the levels of malondialdehyde as a marker of lipid peroxidation in
      ischemic tissue, and the results indicate that propofol plays a role in the
      inhibition of neuronal death induced by brain ischemia.

PMID- 11954773
TI  - Chiari type I presenting as left glossopharyngeal neuralgia with cardiac syncope.
AB  - Glossopharyngeal neuralgia is an uncommon craniofacial pain syndrome that is
      occasionally associated with cardiac syncope. However, we relate Chiari I
      syndrome as a cause of this clinical picture for the first time in the
      literature. The authors analyze the relevant literature and discuss the
      pathogenesis and treatment of associated syndromes. We describe the case of a 45
      year-old female patient who presented with a 3-year history of left
      glossopharyngeal neuralgia with occasional dysphagia and episodes of syncope when
      eating or swallowing. The pain was not disseminated to the right side and was
      fairly well controlled by carbamazepine. The syncopal attacks had a duration of
      about 10 sec. Neurological examination elicited a faint dysphonia associated with
      paradoxical dysphagia. The cranial magnetic resonance imaging scan showed a
      bilateral herniation of the cerebellar tonsils through the foramen magnum, more
      evidently on the left side. The patient received a suboccipital craniectomy and
      resection of the posterior arch of C1. The dura mater was opened, and we found
      both tonsils displaced into the foramen magnum extending caudally toward the C1
      level. Both tonsils were compressing the brainstem and especially the low cranial
      nerves bilaterally. The lower cranial nerves were compressed between the
      posterior inferior cerebellar artery (PICA) and the herniated cerebellar tonsil
      on both sides. Both PICAs were dissected by microsurgical technique and all the
      arachnoid adherences were cut. The left tonsil was resected by means of
      ultrasonic aspirator. Duraplasty was performed with the occipital pericranium.
      The paroxysmal pain attacks and the syncopal picture disappeared immediately
      after the operation. The patient was discharged on the 7th postoperative day. One
      year later, she was free of symptoms. This case provides clinical evidence of
      close connections between the glossopharyngeal and vagus nerves, which control
      visceral sensation; and compression of the IX and X nerves between the herniated
      tonsil and PICA or vertebral artery may cause an irritative sensory phenomenon,
      which is the origin of the algic sensation and the cardiac syncope by means of
      cross talk between the fibers of the same nerve.

PMID- 11954774
TI  - Changes in fluorescein angiogram early after surgical removal of choroidal
      neovascularization in age-related macular degeneration.
AB  - BACKGROUND: Retinal pigment epithelial (RPE) defects inevitably occur in surgical
      removal of choroidal neovascularization (CNV) in age-related macular degeneration
      (AMD). RPE can proliferate and cover the denuded area, but the healing process
      has not been investigated in humans. To understand the RPE wound-healing process,
      we estimated the changes in fluorescein angiograms early after CNV removal.
      METHODS: Ten consecutive patients with exudative AMD underwent CNV removal
      without gas tamponade. Fluorescein angiography was performed within 4 days of
      surgery and again 1 or 2 weeks postoperatively. Areas of leakage were measured
      using a computer-assisted image analyser. The decreasing rate of leakage was
      calculated as the change in disc areas of leakage per day (DA/day). RESULTS: The
      rates of decreasing leakage ranged from 0 to 0.42 DA/day (mean, 0.24 +/- 0.15
      DA/day; median, 0.26 DA/day). The rate of decreasing leakage correlated with
      changes in visual acuity (r = 0.642, P = 0.0456). CONCLUSION: The retinal pigment
      epithelial wound after surgical removal of choroidal neovascularization may heal
      at the rate of 0.24 disc areas/day based on the blood retinal barrier function in
      patients with age-related macular degeneration. A faster rate of decreasing
      leakage may be associated with better visual prognosis.

PMID- 11954775
TI  - Perioperative cataract OP management by means of teleconsultation.
AB  - BACKGROUND: Teleconsultation services have the potential to improve the
      communication among different medical care providers and between them and the
      patient. Increasing effectiveness in the shape of a savings in time or cost is
      often the result of better communication. METHODS: A study was performed in order
      to demonstrate the feasibility of teleconsultation services, using the
      perioperative management of cataract patients as an example, and to provide data
      on the quality, acceptance and effectiveness of these services in comparison with
      a control group experiencing normal treatment. RESULTS: Over a period of 3 months
      42 patients of the teleconsultation group and 20 controls were studied. There
      were two referring ophthalmologists and three surgeons. The teleconsultation
      group had one consultation fewer with the ophthalmic surgeon because of the
      teleconsultation service. Patient satisfaction was slightly higher using the new
      technology. Patients would like to see this technique used again should surgery
      on the second eye become necessary. CONCLUSIONS: Teleconsultation services are
      ready to support and improve perioperative cataract management. Patients'
      confidence in their medical treatment was increased by using teleconsultation
      services. Physicians will expand the use of teleconsultation.

PMID- 11954776
TI  - Long-term results of cataract surgery combined with trabeculotomy.
AB  - BACKGROUND: There are different surgical approaches for cataract and concomitant
      primary open-angle glaucoma (POAG). In a retrospective study we examined the long
      term results of cataract extraction combined with trabeculotomy. PATIENTS AND
      METHODS: Between 1990 and 1997, 194 eyes with cataract and POAG were operated on
      in a combined manner. Eighty-eight eyes received a trabeculotomy (TT), in 82 eyes
      a trabeculectomy was added to the trabeculotomy (TT+TE) and in 24 eyes, in which
      probing of Schlemm's canal was impossible, standard trabeculectomy (TE) was
      performed. Pre- and postoperative intraocular pressure (IOP), glaucoma
      medication, and the intra- and postoperative complications of all patients were
      analyzed. RESULTS: Hyphema was the most common complication in the TT group
      (20.5%). Fibrin reaction occurred in 27.8% of all cases. There was no
      statistically significant difference in postoperative IOP between the TT group
      and the TT+TE group. A statistically significant decrease in IOP compared to
      preoperatively lasted 60 months in the TT group. In eyes with a preoperative IOP
      < or = 20 mmHg, none of the three procedures reduced IOP significantly (<20% of
      the preoperative IOP). In the first 2 years after operation 50% of the patients
      had no need for antiglaucomatous medication. CONCLUSIONS: Cataract surgery
      combined with TT resulted in few complications. In low-tension glaucoma the
      combination with TT is not sufficient to decrease the IOP. In patients with
      higher preoperative IOP, however, cataract surgery combined with TT could be--on
      the basis of a postoperative observation time of 72 months--a suitable method for
      lowering the IOP sufficiently. Furthermore, the use of antiglaucomatous
      substances was reduced by this combined procedure.

PMID- 11954777
TI  - Effect of simultaneous oblique muscle surgery in foveal translocation by 360
      degrees retinotomy.
AB  - PURPOSE: To assess the effect of simultaneous oblique muscle surgery during
      foveal translocation surgery with 360 degrees retinotomy in patients with
      neovascular maculopathy. METHODS: Foveal translocation with 360 degrees
      retinotomy was performed on 31 eyes of 31 patients with neovascular maculopathy
      (21 with age-related macular degeneration 9 with myopic neovascular maculopathy,
      and 1 with idiopathic neovascular maculopathy). All eyes had simultaneous
      torsional muscle surgery with recession of the superior oblique muscle and
      tucking of the inferior oblique muscle. Visual acuity, binocular vision, and
      degree of cyclotorsion were assessed pre- and postoperatively. The angles of
      retinal and global rotation, distance of foveal shift, and surgical complications
      were also investigated. RESULTS: With a mean postoperative follow-up of 10.0
      months, vision improved (>0.2 log MAR units) in 13 eyes, was unchanged in 9 eyes,
      and worsened (>0.2 log MAR units) in 9 eyes. Ten of 31 eyes (32%) had a final
      visual acuity of 20/50 or better. Eleven patients had binocular fusion, 13
      patients showed suppression, and 7 patients developed diplopia that was managed
      by spectacles with prisms or by secondary muscle surgery. The mean retinal and
      global rotations were 30.3 degrees and 23.7 degrees, respectively. The average
      size of the choroidal neovascular membrane was 1.3 disc diameters (DD), while the
      average shift of the fovea was 1.5 DD. After the primary surgery, six eyes
      developed retinal detachment, two eyes macular hole, and three eyes proliferative
      vitreoretinopathy. These complications were successfully managed by additional
      surgery. CONCLUSION: Foveal translocation with 360 degrees retinotomy is
      effective in restoring vision in 40% of patients with neovascular maculopathy.
      Simultaneous oblique muscle surgery was effective in rotating the globe by about
      20 degrees, corresponding to to a foveal shift of 1.5 DD. While the development
      of torsional diplopia is generally prevented by simultaneous oblique muscle
      surgery, the relatively high incidence of surgical complications with this
      procedure should be taken into account.

PMID- 11954778
TI  - Presentation delay in patients affected with exudative age-related macular
      degeneration.
AB  - BACKGROUND: Presentation delay (i.e. duration of visual symptoms before initial
      presentation) is an established critical parameter for visual prognosis in
      patients with exudative age-related macular degeneration (ARMD) considering the
      natural history of the disease and the limitations of current treatments. The
      purpose of this study was to determine the duration of presentation delay and its
      evolution in two periods 4 years apart. METHODS: Presentation delay in 1598
      patients affected with exudative ARMD was retrospectively reviewed during two
      similar 8-month periods in 1994 and 1998 in a tertiary referral center. RESULTS:
      The proportions of patients examined either within 1 month, between 1 and 3
      months, and between 3 and 6 months after onset of symptoms, respectively,
      increased between 1994 and 1998 from 23% to 33%, from 27% to 32.5%, and from 14%
      to 18.5%. The proportions of patients examined between 6 and 12 months and after
      12 months decreased from 16% to 12% and from 20% to 4%, respectively.
      Furthermore, the proportion of patients presenting with a first eye involvement
      during the first month following the onset of symptoms rose from 42% in 1994 to
      52% in 1998. All these differences were statistically significant. CONCLUSION:
      This first specific review of presentation delay in exudative ARMD showed a
      significant decrease in this parameter between 1994 and 1998 that should be taken
      into account when assessing the overall evolution of visual outcome. Further
      studies are warranted to ascertain that these findings reflect a global
      improvement in the management of macular diseases.

PMID- 11954779
TI  - Effects of autologous platelet concentrate and serum on retinal wound healing in
      an animal model.
AB  - BACKGROUND: The beneficial effects of adjuvant treatment with agents such as
      autologous platelet concentrate (APC) or autologous serum (AS) in the surgical
      management of macular holes remain uncertain. The purpose of this study was to
      determine the histological changes induced by these agents compared with control
      on retinal wound healing in an animal model. METHODS: The right eyes of 51
      pigmented rabbits were used. Under anaesthesia, full-thickness sensory retinal
      incisions 2 mm in length were made into avascular retina down to the level of the
      retinal pigment epithelium using a 23-gauge needle via a superotemporal
      sclerotomy. APC, AS or sterilised balanced salt solution was placed directly over
      the wound site. Animals were killed at 3, 7 or 14 days and the wounds examined
      immunohistologically. Proliferating cell nuclear antigen (PCNA) was used to
      detect proliferating cells. RESULTS: No difference was observed between serum
      treated eyes and control eyes. A greater displacement or migration of cells
      toward the retinal surface was consistently found in the APC-treated wounds than
      in control wounds. These cells were of mixed origin but appeared to arise
      predominantly from the outer nuclear layer. A significantly greater number of
      PCNA-staining cells was found in the platelet-treated group than in controls at 3
      days (P=0.038), 7 days (P=0.039) and 14 days (P=0.038). CONCLUSION: We have
      demonstrated a significantly greater proliferative cellular response in the
      healing of retinal wounds with the use of platelet concentrate than in control
      wounds. We consider that this model may be used in further studies on the effects
      of other agents on retinal wound healing.

PMID- 11954780
TI  - Inhibitory effects of triamcinolone acetonide on bFGF-induced migration and tube
      formation in choroidal microvascular endothelial cells.
AB  - BACKGROUND: Angiostatic drugs might provide desirable modulation of choroidal
      angiogenesis-related diseases, including histoplasmosis and the exudative form of
      age-related macular degeneration. However, the precise effects of this class of
      compounds in the choroidal neovascularization are still unclear. In the present
      study, we investigated the effects of triamcinolone acetonide (TA), an
      angiostatic steroid, on choroidal angiogenesis in vitro. METHODS: Bovine
      choroidal endothelial cells (CEC), which are the critical cellular component of
      choroidal angiogenesis in vivo, were isolated with Lycopersicon esculentum
      agglutinin-coated Dynabeads and cultured in EGM medium. CEC were treated with
      basic fibroblast growth factor (bFGF) and TA at various concentrations ranging
      from 50 to 300 mg/l. The capacities for CEC migration and tube formation were
      evaluated with the modified Boyden chamber and the Vitrogen collagen assay,
      respectively. The activities of matrix metalloproteinases (MMP)-2 and -9 were
      examined using gelatin zymography. RESULTS: The stimulation of CEC with 50 ng/ml
      bFGF resulted in an increase of about 100% in migration activity (P<0.01).
      Preincubation of CEC with TA at the indicated concentrations for 20 min inhibited
      the bFGF-stimulated migration in a dose-dependent manner (P<0.01). After 5 days,
      the bFGF-stimulated tube formation in CEC was inhibited by TA at the
      concentrations 100, 150 and 300 mg/l (P<0.01). Gelatin zymography of the culture
      media of CEC showed that the bFGF-induced activation of MMP-2 was attenuated by
      300 mg/l TA (P<0.05). CONCLUSION: Downregulation of the activation of MMPs in CEC
      could be one of the mechanisms by which angiostatic steroids inhibit choroidal
      angiogenesis.

PMID- 11954781
TI  - Analysis of immediate changes of water-soluble metabolites in alkali-burned
      rabbit cornea, aqueous humor and lens by high-resolution 1H-NMR spectroscopy.
AB  - PURPOSE: To investigate immediate changes in water-soluble metabolites of ocular
      tissue in alkali-burned eyes by using high-resolution 1H-NMR spectroscopy.
      METHODS: Adult New Zealand rabbit eyes were burned with 1 M NaOH for 1 min.
      Normal eyes were used as control. Samples from aqueous humor and perchloric acid
      extracts of the cornea and lens were analyzed on a NMR spectrometer operating at
      500 MHz for protons. Metabolites were quantified by comparing peak area with an
      added internal standard, TSP (3'-trimethylsilylpropinate-2,2,3,3-d4). RESULTS:
      Alkali burn of corneal surface causes immediate changes in concentration of many
      water-soluble metabolites in the anterior segment. Even as far away as the lens a
      significant increase in lactate was found. Cornea showed a significant increase
      in glucose and a significant decrease in hypo-taurine concentration. Most changes
      were observed in aqueous humor, with significant increases in succinate,
      creatine, scyllo- and myo-inositol and a significant decrease in citrate
      concentration. Furthermore, a small decrease in ascorbate concentration in
      aqueous humor was observed. CONCLUSIONS: The present study provides a valuable
      contribution to the knowledge of metabolic alterations in alkali-burned eyes. It
      shows that 1H-NMR spectroscopy is well suited for simultaneous qualitative and
      quantitative analysis of changes of metabolite concentrations in damaged tissues.
      This can help us to better evaluate and understand the biological alterations due
      to alkali burn.

PMID- 11954782
TI  - Posterior vitreous detachment with plasmin in the isolated human eye.
AB  - PURPOSE: To investigate the efficacy and safety of intravitreal injection of
      plasmin in producing posterior vitreous detachment (PVD), and the possible role
      of plasmin in degrading adhesion glycoproteins of the internal limiting membrane
      (ILM). METHODS: A total of 20 young human cadaver eyes were randomized into four
      groups. Groups 1, 2, and 3 were injected with 1, 2, and 3 U of human plasmin,
      respectively, and group 1 was injected with 0.1 ml balanced salt solution as
      control. Optical and transmission electron microscopy were used to examine the
      ultrastructure of the vitreoretinal interface. The amounts of fibronectin (FN)
      and laminin (LN) in the ILM were determined using electron-immunocytochemical
      techniques. The survival of retinal cells was evaluated using flow cytometry.
      Analysis of variance (ANOVA) and the Tukey test were used for statistical
      analysis. RESULTS: Microscopy showed that plasmin, especially in group 4, cleaved
      the attachment of the vitreous collagen fibrils to the ILM. There was no evidence
      of damage to the inner retina except some post-mortem lytic changes. The amounts
      of LN and FN in the ILM were decreased following injection of plasmin. There were
      statistically significant differences in the amounts of FN in groups 3 and 4
      compared to the control group (P<0.05), and in the amount of LN in group 4
      (P<0.05). Retinal cell viability was similar in both treated and control eyes.
      CONCLUSION: Human plasmin can disrupt the attachment of the posterior hyaloid to
      the ILM without producing morphological changes or acute toxicity of the inner
      retina of the human eye. PVD can be induced completely by injection of 3 U
      plasmin. The enzyme may be useful for removing the cortical vitreous during
      vitreous surgery.

PMID- 11954783
TI  - Vitreous phenotype: genotype correlation in Stickler syndrome.

PMID- 11954784
TI  - Hyperfluorescence at arteriovenous crossing before branch retinal vein occlusion.

PMID- 11954785
TI  - Transpupillary thermotherapy (TTT) in circumscribed choroidal hemangioma.
AB  - BACKGROUND: Choroidal hemangioma presents a therapeutic dilemma. Although it is a
      benign tumor, it may lead to massive exudation of subretinal fluid and a loss of
      visual function. Argon laser photo-coagulation in a grid pattern may be followed
      by initial absorption of subretinal fluid, but recurrence is common. Trans
      scleral cryotherapy is difficult to apply at the posterior pole of the eye.
      External beam irradiation may bear a risk of maculopathy and papillopathy.
      Brachytherapy does not allow placement of radiation to the hemangioma sparing
      other retinal or choroidal structures. We sought to determine whether
      transpupillary thermotherapy (TTT) is suitable for treatment of choroidal
      hemangioma at the posterior pole. METHODS: We present ten patients with choroidal
      hemangioma. All of these received TTT. The mean follow-up period was 13.3 months
      (3-21 months). TTT was delivered via a slitlamp microscope with a diode laser at
      810 nm. RESULTS: After TTT, reduction in tumor prominence was observed in eight
      patients at 3 months after treatment by A scan sonography. Visual acuity improved
      by more than three lines in four patients, and remained unchanged in all other
      patients. Two patients were retreated to achieve complete absorption of fluid.
      Serous retinal detachment persisted in three patients because the hemangioma
      could not be treated completely because of proximity to the fovea. CONCLUSION:
      Our preliminary results suggest that TTT may be used effectively to treat some
      choroidal hemangiomas in the first instance and prevent fluid leakage provided
      the lesion does not involve the fovea. However, long-term follow-up and more
      cases are needed to evaluate the long-term visual outcome and potential risks.

PMID- 11954786
TI  - Myco-protein from Fusarium venenatum: a well-established product for human
      consumption.
AB  - Fusarium venenatum A3/5 was first chosen for development as a myco-protein in the
      late 1960s. It was intended as a protein source for humans and after 12 years of
      intensive testing, F. venenatum A3/5 was approved for sale as food by the
      Ministry of Agriculture, Fisheries and Food in the United Kingdom in 1984. Today,
      myco-protein is produced in two 150,000 l pressure-cycle fermenters in a
      continuous process which outputs around 300 kg biomass/h. The continuous process
      is typically operated for around 1,000 h. One factor which has limited the length
      of production runs was the appearance of highly branched mutants in the
      population. Several factors affect the time of appearance of such mutants and a
      number of strategies for delaying their appearance have been investigated. After
      reduction of the RNA content, the fungal biomass is mixed with egg albumin and
      made into a variety of products. Consumption of these can lead to reduced blood
      cholesterol and to lower energy intake in a subsequent meal. E venenatum myco
      protein is now used in products available in six European countries and there are
      plans for it to be sold in France, the United States and Germany.

PMID- 11954787
TI  - An update on the use of unconventional substrates for biosurfactant production
      and their new applications.
AB  - Biosurfactants are valuable microbial amphiphilic molecules with effective
      surface-active and biological properties applicable to several industries and
      processes. Microbes synthesize them, especially during growth on water-immiscible
      substrates, providing an alternative to chemically prepared conventional
      surfactants. Because of their structural diversity (i.e., glycolipids,
      lipopeptides, fatty acids, etc.), low toxicity, and biodegradability, these
      molecules could be widely used in cosmetic, pharmaceutical, and food processes as
      emulsifiers, humectants, preservatives, and detergents. Moreover, they are
      ecologically safe and can be applied in bioremediation and waste treatments. They
      can be produced from various substrates, mainly renewable resources such as
      vegetable oils, distillery and dairy wastes, which are economical but have not
      been reported in detail. In this review, we report advances made in using
      renewable substrates for biosurfactant production and their newer applications.

PMID- 11954788
TI  - Draw-fill batch culture mode for production of xylanases by Cellulomonas
      flavigena on sugar cane bagasse.
AB  - Draw-fill culture was evaluated as a method for xylanase production by
      Cellulomonas flavigena on sugar cane bagasse. Specific xylanase activity and
      volumetric xylanase activities were measured by harvesting 50%, 55%, 60% and 70%
      of fermented broth at the end of each subculture. Maximum specific (64 IU mg(-1)
      protein) and volumetric (166 IU ml(-1)) xylanase activities were obtained by
      harvesting 50-55% of broth. Values were 3.4 and 3.8 times greater than those
      obtained in batch cultures carried out under the same conditions. Enzyme
      productivity of 4.2 IU ml(-1) h(-1) was significantly greater than that obtained
      in continuous cultures (2.4 IU ml(-1) h(-1)) (P<0.05).

PMID- 11954789
TI  - Purification and characterization of a recombinant beta-galactosidase with
      transgalactosylation activity from Bifidobacterium infantis HL96.
AB  - A beta-galactosidase isoenzyme, beta-Gall, from Bifidobacterium infantis HL96,
      was expressed in Escherichia coli and purified to homogeneity. The molecular mass
      of the beta-Gall subunit was estimated to be 115 kDa by SDS-PAGE. The enzyme
      appeared to be a tetramer, with a molecular weight of about 470 kDa by native
      PAGE. The optimum temperature and pH for o-nitrophenyl-beta-D-galactopyranoside
      (ONPG) and lactose were 60 degrees C, pH 7.5, and 50 degrees C, pH 7.5,
      respectively. The enzyme was stable over a pH range of 5.0-8.5, and remained
      active for more than 80 min at pH 7.0, 50 degrees C. The enzyme activity was
      significantly increased by reducing agents. Maximum activity required the
      presence of both Na+ and K+, at a concentration of 10 mM. The enzyme was strongly
      inhibited by p-chloromercuribenzoic acid, divalent metal cations, and Cr3+, and
      to a lesser extent by EDTA and urea. The hydrolytic activity using lactose as a
      substrate was significantly inhibited by galactose. The Km, and Vmax values for
      ONPG and lactose were 2.6 mM, 262 U/mg, and 73.8 mM, 1.28 U/mg, respectively.
      beta-Gall possesses strong transgalactosylation activity. The production rate of
      galactooligosaccharides from 20% lactose at 30 and 60 degrees C was 120 mg/ml,
      and this rate increased to 190 mg/ml when 30% lactose was used.

PMID- 11954790
TI  - High production of heterologous proteins in Escherichia coli using the thermo
      regulated T7 expression system.
AB  - The exclusive use of isopropyl beta-D-thiogalactopyranoside to activate the T7
      promoter for protein production has limited the general use of the expression
      system. We have sought an alternative by constructing a recombinant Escherichia
      coli strain, BL21 (G2), to carry a chromosomal copy of T7 gene 1 fused to the
      lambdaPL and lambdaP(R) tandem promoter. As a result, the recombinant strain
      harboring the carbamoylase gene from Agrobacterium radiobacter NRRL B11291 was
      shown to display various levels of.protein production in response to different
      degrees of heat shock. In particular, the system remained inactive at 30 degrees
      C and exhibited high sensitivity to heat such that a detectable carbamoylase
      activity could be measured after exposure to 33 degrees C. Moreover, heating in
      two steps - elevating the temperature from 30 degrees C to 39 degrees C and
      holding for a brief period, followed by reducing to 37 degrees C--was found to be
      the most potent method for protein production in this case. Using this approach,
      the recombinant protein accounted for 20% of total protein content of the cell.
      These results reveal the advantages of this expression system: responsiveness to
      thermal modulation and high-level production capability. In an attempt to enhance
      the total protein yield, a fed-batch fermentation process was carried out to
      control the cell growth rate by adjusting the substrate inflow. By applying the
      two-step temperature change. a carbamoylase yield with enzyme activity
      corresponding to 14,256 units was obtained. This production yield is a 10-fold
      increase in comparison with that at the batch-fermentation scale and 2,000-fold
      higher than that achieved at the shake-flask scale. Overall, it illustrates the
      promise of the newly constructed T7 system based on heat inducibility for
      industrial scale production of recombinant proteins.

PMID- 11954791
TI  - Transformation of the Pseudonocardiaceae amycolatopsis sp. strain HR167 is highly
      dependent on the physiological state of the cells.
AB  - The Pseudonocardiaceae Amycolatopsis sp. strain HR167 is used in a
      biotransformation process to produce vanillin from ferulic acid. To make this
      strain accessible for genetic engineering, a direct mycelium transformation
      system developed for Amycolatopsis mediterranei [Madon and Hotter (1991) J
      Bacteriol 173: 6325-6331] was applied and optimized for Amycolatopsis sp. strain
      HR167. The physiological state of the cells had a major influence on the
      transformation rate. The highest transformation rate of about 7x10(5)
      transformants per microgram of DNA was obtained with mycelium harvested 6.5-7.5 h
      after the culture has reached the stationary growth phase. When cells were
      harvested outside of this time slot, the transformation rate drastically
      decreased. The density of the mycelium suspensions used in the transformation
      mixture and the methylation state of the plasmid DNA used for the transformation
      were also crucial parameters. With plasmid DNA isolated from Escherichia coli
      ET12567, transformation rates were 3,500-fold higher than those obtained with DNA
      isolated from E. coli XL1-Blue.

PMID- 11954792
TI  - Constitutive expression of the Trichoderma reesei beta-1,4-xylanase gene (xyn2)
      and the beta-1,4-endoglucanase gene (egl) in Aspergillus niger in molasses and
      defined glucose media.
AB  - The xylanase II (xyn2)- and endoglucanase I (egl)-encoding regions of Trichoderma
      reesei QM6a were successfully expressed in Aspergillus niger D15 under the
      transcriptional control of the glyceraldehyde-6-phosphate dehydrogenase (gpd)
      promoter from A. niger and the glaA terminator of Aspergillus awamori. A stable
      xyn2 transformant produced beta-xylanase activity of 8,000 nkat/ml and 5,000
      nkat/ml in shake-flask cultures containing defined or 20% (v/v) molasses medium,
      respectively. The recombinant Xyn2 enzyme expressed highest activity at pH 5-6
      and 50-60 degrees C and retained more than 75% of its activity after 3 h of
      incubation at 50 degrees C. A stable egl transformant produced endo-P-1,4
      glucanase activity of 2,300 nkat/ml in shake-flask cultures containing defined
      media and about half the activity in 20% molasses medium. Maximum endoglucanase
      activity was obtained at pH 5 and 60 degrees C. Both Xyn2 and EgI retained >80%
      activity after incubation at 50 degrees C for 3 h. The heterologous Xyn2 and EgI
      represent a significant portion of the total extracellular proteins produced.

PMID- 11954793
TI  - Identification and characterization of the AgmR regulator of Pseudomonas putida:
      role in alcohol utilization.
AB  - Two-phase partitioning bioreactors (TPPBs) comprise an aqueous phase containing
      all non-carbon nutrients necessary for microbial growth and a solvent phase
      containing high concentrations of inhibitory or toxic substrates that partition
      at sub-inhibitory levels to the aqueous phase in response to cellular demand.
      This work aimed at eliminating the growth of Pseudomonas putida ATCC 11172 on
      medium-chain-length (C8-C12) aliphatic alcohols, hence enabling their use as
      xenobiotic delivery solvents within two-phase partitioning bioreactors.
      Experiments resulted in the isolation of a mini-Tn5 mutant unable to utilize
      these alcohols. The mutation, which also eliminated growth on glycerol and
      ethanol, was identified to be within a homologue of the P aeruginosa agmR gene,
      which encodes a response regulator. Enzyme analysis of the agmR::Tn5Km mutant
      cell extracts revealed a 10-fold decrease in pyrroloquinoline quinone (PQQ)
      dependent alcohol dehydrogenase activity. A knockout in a gene (exaA) encoding a
      PQQ-linked alcohol dehydrogenase slowed but did not eliminate growth on medium
      chain-length alcohols or ethanol, suggesting metabolic redundancy within P.
      putida ATCC 11172. Analysis of P. putida KT2440 genome sequence data indicated
      the presence of two PQQ-linked alcohol dehydrogenase-encoding genes. The
      successful elimination of alcohol utilization in the agmR mutant indicates
      control by AgmR on multiple pathways and presents a useful strain for
      biotechnological applications requiring alcohol non-utilizing microbial
      catalysts.

PMID- 11954794
TI  - Electrically enhanced ethanol fermentation by Clostridium thermocellum and
      Saccharomyces cerevisiae.
AB  - Ethanol production by Clostridium thermocellum ATCC 35609 and Saccharomyces
      cerevisiae ATCC 26603 was improved in an electrochemical bioreactor system. It
      was increased by 61% with Cl. thermocellum and 12% with S. cerevisiae in the
      presence of -1.5 V of electric potential. These increases were attributed to high
      production rates due to regeneration and availability of increased reduced
      equivalents in the presence of electric potential. The electric current caused
      considerable shift in the metabolite concentrations on a molar basis in Cl.
      thermocellum fermentation but less in S. cerevisiae fermentation. Increasing
      electric potential in Cl. thermocellum fermentation resulted in less acetate and
      more lactate production. Acetate production was also reduced with increased
      electric potential in S. cerevisiae fermentation. The high electric potential of 
      5 V adversely affected the Cl. thermocellum fermentation, but not the S.
      cerevisiae fermentation even at a high electric potential of -10 V.

PMID- 11954795
TI  - Growth of sulfate-reducing bacteria with solid-phase electron acceptors.
AB  - Hannebachite (CaSO3 x 0.5H2O), gypsum (CaSO4 x 2H2O), anglesite (PbSO4), and
      barite (BaSO4) were tested as electron acceptors for sulfate-reducing bacteria
      with lactate as the electron donor. Hannebachite and gypsum are commonly
      associated with flue gas desulfurization products, and anglesite is a weathering
      product found in lead mines. Barite was included as the most insoluble sulfate.
      Growth of sulfate-reducing bacteria was monitored by protein and sulfide
      (dissolved H2S and HS-) measurements. Biogenic sulfide formation occurred with
      all four solid phases, and protein data confirmed that bacteria grew under these
      electron acceptor conditions. Sulfide formation from gypsum was almost comparable
      in rate and quantity to that produced from soluble sulfate salt (Na2SO4);
      hannebachite reduction to sulfide was not as fast. Anglesite as the electron
      acceptor was also reduced to sulfide in the solution phase and galena (PbS) was
      detected in solids retrieved from spent cultures. Barite as the electron acceptor
      supported the least amount of growth and H2S formation. The results demonstrate
      that low-solubility crystalline phases can be biologically reactive under
      reducing conditions. Furthermore, the results demonstrate that galena
      precipitation through sulfide production by sulfate-reducing bacteria serves as a
      lead enrichment mechanism, thereby also alleviating the potential toxicity of
      lead. In view of the role of acidophilic thiobacilli in the oxidation of
      sulfides, the present work accentuates the role of anaerobic and aerobic microbes
      in the biogeochemical cycling of solid-phase sulfates and sulfides.

PMID- 11954796
TI  - Overproduction of BiP negatively affects the secretion of Aspergillus niger
      glucose oxidase by the yeast Hansenula polymorpha.
AB  - We have cloned the Hansenula polymorpha BIP gene from genomic DNA using a PCR
      based strategy. H. polymorpha BIP encodes a protein of 665 amino acids, which
      shows very high homology to Saccharomvces cerevisiae KAR2p. KAR2p belongs to the
      Hsp70 family of molecular chaperones and resides in the endoplasmic reticulum
      (ER)-lumen. H. polymorpha BiP contains a putative N-terminal signal sequence of
      30 amino acids together with the conserved -HDEL sequence, the typical ER
      retention signal, at the extreme C-terminus. We have analysed the effect of BIP
      overexpression, placing the gene under control of the strong alcohol oxidase
      promoter (P(MOX)) on the secretion of artificially produced Aspergillus niger
      glucose oxidase (GOX) by H. polymorpha. BiP overproduction did not lead to any
      growth defects of the cells; at the subcellular level, proliferation of ER-like
      vesicles was observed. However, artificially enhanced BiP levels strongly
      affected GOX secretion and led to accumulation of this protein in the ER-like
      vesicles. This was not simply due to the high BiP overproduction, because it was
      also observed under conditions of low P(MOX) induction during growth of cells on
      glycerol. Vacuolar carboxypeptidase Y was properly sorted to its target organelle
      in the BiP overproducing strains.

PMID- 11954797
TI  - Growth physiology and dimorphism of Mucor circinelloides (syn. racemosus) during
      submerged batch cultivation.
AB  - Mucor circinelloides is being investigated as a possible host for the production
      of heterologous proteins. Thus, the environmental conditions defining the
      physiology and morphology of this dimorphic fungus have been investigated in
      submerged batch cultivation. The optimal conditions for growth of each form have
      been defined. Pure cultures of the multi-polar budding yeast form could be
      obtained under anaerobic conditions (with 70% N2/30% CO2 or 100% N2 as the sparge
      gas and without aeration). The highest maximum specific growth rate (0.30 h(-1))
      was obtained in anaerobic cultivation, the yield of biomass on glucose (Y(SX))
      was 0.12 (c-mole basis). A high maximum specific growth rate was obtained when
      the organism grew as the filamentous form under aerobic conditions (0.25 h(-1)),
      with a Y(SX) of 0.24 (c-mole basis). The maximum specific growth rates achieved
      are comparable to most industrial filamentous fungi under similar growth
      conditions. High levels of ethanol were observed with all growth conditions. The
      overriding effector of morphological development was found to be oxygen. In batch
      cultures it was therefore possible to induce the dimorphic shift by controlling
      the influent gas atmosphere. A specific growth rate of 0.19 h(-1) was maintained
      during the shift from the yeast to the filamentous form.

PMID- 11954798
TI  - Production of volatile compounds by cheese-ripening yeasts: requirement for a
      methanethiol donor for S-methyl thioacetate synthesis by Kluyveromyces lactis.
AB  - Five cheese-ripening yeasts (Geotrichum candidum, Saccharomyces cerevisiae,
      Kluyveromyces lactis, Yarrowia lipolytica and Debaryomyces hansenii) were
      compared with respect to their ability to generate volatile aroma compounds. K.
      lactis produced a variety of esters - ethylacetate (EA) being the major one - and
      relatively limited amounts of volatile sulphur compounds (VSCs). Conversely, G.
      candidum produced significant amounts of VSCs [with the thioester S-methyl
      thioacetate (MTA) being the most prevalent] and lower quantities of non-sulphur
      volatile compounds than K. lactis. We suspect that K. lactis is able to produce
      and/or accumulate acetyl CoA - a common precursor of MTA and EA - but that it
      produces limited amounts of methanethiol (MTL); both acetyl CoA and MTL are
      precursors for MTA synthesis. When supplemented with exogenous MTL, MTA
      production greatly increased in K. lactis cultures whereas it was unchanged in G.
      candidum cultures, suggesting that MTL is a limiting factor for MTA synthesis in
      K. lactis but not in G. candidum. Our results are discussed with respect to L
      methionine catabolism.

PMID- 11954799
TI  - Controlled transient changes reveal differences in metabolite production in two
      Candida yeasts.
AB  - Physiological responses during growth on xylose and the xylose-degrading pathway
      of Candida tropicalis and Candida guilliermondii yeasts were investigated. The
      responses to a linearly decreasing oxygen transfer rate and a simultaneously
      increasing dilution rate were compared. C. guilliermondii produced acetate but no
      ethanol, and C. tropicalis ethanol but no acetate under oxygen limitation. Both
      strains produced glycerol. The D-xylose reductase of C. guilliermondii is
      exclusively NADPH-dependent. and acetate production regenerated NADPH. The
      xylose'reductase of C. tropicalis has a dual dependency for both NADH and NADPH.
      It regenerated NAD by producing ethanol. Both strains regenerated NAD by
      producing glycerol. The effect of intracellular NADH accumulation to xylose
      uptake and metabolite production was studied by using formate as a cosubstrate.
      Formate feeding in C. tropicalis triggered the accumulation of glycerol, ethanol
      and xylitol. Consequently, the specific xylose consumption increased 28% during
      formate feeding, from 477 to 609 C-mmol/C-mol cell dry-weight (CDW)/h. In C.
      guilliermondii cultures. formate feeding resulted only in glycerol accumulation.
      The specific xylose consumption increased 6%, from 301 to 319 C-mmol/C-mol CDW/h,
      until glycerol started to accumulate.

PMID- 11954800
TI  - Metabolic response against sulfur-containing heterocyclic compounds by the lignin
      degrading basidiomycete Coriolus versicolor.
AB  - The fungal conversions of sulfur-containing heterocyclic compounds were
      investigated using the lignin-degrading basidiomycete Coriolus versicolor. The
      fungus metabolized a series of sulfur compounds--25 structurally related
      thiophene derivatives--via several different pathways. Under primary metabolic
      conditions, C. versicolor utilized thiophenes, such as 2-hydroxymethyl-, 2-formyl
      , and 2-carboxyl-thiophenes, as a nutrient sulfur source for growth; thus, the
      fungus degraded these compounds more effectively in a non-sulfur-containing
      medium than in conventional medium. The product analysis revealed that several
      redox reactions, decarboxylation reactions, and C-S cleavage reactions were
      involved in the fungal conversion of non-aromatic thiophenes. On the other hand,
      benzothiophene (BT) and dibenzothiophene (DBT) skeletons were converted to water
      soluble products. All the products and metabolic intermediates were more
      hydrophilic than the starting substrates. These metabolic actions seemed to be a
      chemical stress response against exogenously added xenobiotics. These metabolic
      reactions were optimized under ligninolytic conditions, also suggesting the
      occurrence of a fungal xenobiotic response. Furthermore, the fungus converted a
      series of BTs and DBTs via several different pathways, which seemed to be
      controlled by the chemical structure of the substrates. DBT, 4-methylDBT, 4, 6
      dimethylDBT, 2-methylBT, and 7-methylBT were immediately oxidized to their S
      oxides. BTs and DBTs with the hydroxymethyl substituent were converted to their
      xylosides without S-oxidation. Those with carboxyl and formyl substituents were
      reduced to form a hydroxymethyl group, then xylosidated. These observations
      strongly suggested the involvement of a fungal substrate-recognition and
      metabolic response mechanism in the metabolism of sulfur-containing heterocyclic
      compounds by C. versicolor.

PMID- 11954801
TI  - Influence of spawn rate and commercial delayed release nutrient levels on
      Pleurotus cornucopiae (oyster mushroom) yield, size, and time to production.
AB  - Pleurotus cornucopiae 608 was grown on a mixture of pasteurized cottonseed hulls
      (75% dry wt). 24% chopped wheat straw, and 1% ground limestone. The substrate was
      spawned at various levels (1.25%, 2.5%, 3.75%, or 5% wet wt) and not supplemented
      or supplemented with commercial delayed release nutrient (Campbell's S-41) at
      various levels (0%, 3%, 6%, 9%, or 12%). Maximum yield (weight of fresh mushrooms
      harvested at maturity) was obtained at 3.75-5% spawn level and 6% S-41
      supplement. As supplement levels exceeded 6%, yields declined significantly.
      There was a negative correlation (r=-0.81) between spawn rate and days to
      production. As the spawn rate increased, the number of days to production
      decreased. By using a spawn rate of 3.75% of the wet substrate wt, it was
      possible to reduce the time to production by a mean of 9.2 days compared with a
      spawn rate of 1.25%.

PMID- 11954802
TI  - Interactions between photoautotrophic and heterotrophic metabolism in
      photoheterotrophic cultures of Euglena gracilis.
AB  - Interactions between photoautotrophic and heterotrophic metabolism in
      photoheterotrophic culture of Euglena gracilis were studied. Under a low light
      supply coefficient, these two metabolic activities seem to proceed independently.
      The cell growth rate in photoheterotrophic culture was about the sum of the
      growth rates in pure photoautotrophic and heterotrophic cultures. However under a
      high light supply coefficient, both photoautotrophic and heterotrophic (glucose
      assimilation) metabolic activities were inhibited, resulting in a low
      photoheterotrophic growth rate. The photoheterotrophic culture was more sensitive
      to photoinhibition compared to the pure photoautotrophic culture. Inhibition of
      glucose assimilation in the photoheterotrophic culture was due to both direct and
      indirect (through photosynthesis) effects of high light intensity. Cell growth,
      glucose assimilation and alpha-tocopherol content of the cells were higher when
      ambient air was used for aeration than when a mixture of carbon dioxide and air
      was used. Even when photosynthesis was inhibited by addition of 3-(3,4
      dichlorophenyl)- 1,1-dimethylurea to photoheterotrophic culture, light stimulated
      alpha-tocopherol synthesis by E. gracilis.

PMID- 11954803
TI  - A lipoxygenase inhibitor from Aspergillus niger.
AB  - A lipoxygenase-1 (LOX-1) inhibitor was isolated from the fermented broth of
      Aspergillus niger CFTRI 1105. It was purified, using column and preparative thin
      layer chromatography. 1H NMR and GC-MS examination revealed the structure of the
      inhibitor to be 2-(2'-methyl, 4'-hydroxyphenyl), 2-(4"hydroxyphenyl)-propane with
      a molecular weight of 242 and the molecular formula C,6H18O2. This bisphenol
      derivative inhibitor shows 50% inhibition of soybean LOX-I at 0.98 mM
      concentration. The activity of this inhibitor was compared with commercial
      bisphenol A and its structural analogues, butylhydroxyanisole and
      butylhydroxytoluene in an attempt to understand the role of functional groups
      affecting lipoxygenase activity.

PMID- 11954804
TI  - Isolation of an Acinetobacter sp. ST-550 which produces a high level of indigo in
      a water-organic solvent two-phase system containing high levels of indole.
AB  - Acinetobacter sp. strain ST-550 was isolated from fumus soil as an efficient
      indigo producer in the presence of organic solvent. The minimum inhibitory
      concentration of indole was 0.4 mg/ml for ST-550. ST-550 produced only a small
      amount of indigo (less than 0.01 microg/ml) when grown in the presence of indole
      at concentrations of 0.05 to 0.3 mg/ml without any organic solvent. However. ST
      550 produced indigo effectively when grown in the presence of a large volume of
      diphenylmethane and a high level of indole: optimized conditions were 3 ml of a
      medium containing 0.3 ml diphenylmethane and 2.7 mg indole. Under these
      conditions, ST-550 produced 0.88 mg indigo (292 microg/mI medium).

PMID- 11954805
TI  - Bacillus naphthovorans sp. nov. from oil-contaminated tropical marine sediments
      and its role in naphthalene biodegradation.
AB  - A Bacillus sp., designated as strain MN-003, was isolated as the dominant
      cultivatable naphthalene-degrading organism from oil-contaminated tropical marine
      sediments. Strain MN-003 is strictly aerobic, rod-shaped, Gram-positive, catalase
      positive, oxidase negative, and forms endospores. Strain MN-003 grew at
      salinities ranging from 0.28 to 7.00% and temperatures ranging from 15 to 41
      degrees C. Phylogenetic analyses reveal that strain MN-003 is most similar to
      Bacillus sp. VAN14, with a 16S rRNA sequence identity of 97.9%. Based on
      taxonomic and 16S rRNA data, strain MN-003 was named Bacillus naphthovorans sp.
      nov. When grown with naphthalene as sole carbon source, strain MN-003 had a
      maximal specific growth rate (mu(max)) of 0.32 +/- 0.03 h(-1), and a half
      saturation constant (K(S)) of 22.3 +/-4.2 microM. A batch study of the tropical
      marine sediments enriched with naphthalene showed that cells of the Bacillus
      genus grew to become dominant members of the microbial community. The bacilli
      comprised 39.5 +/- 6.5% of the microbial fraction after 20 days of enrichment.

PMID- 11954806
TI  - Comparison of single-phase and high-frequency generators for x-ray units.
AB  - The purpose of this study was to compare characteristics and performances between
      single-phase (SP) and high-frequency (HF) generators for x-ray units dedicated to
      veterinary radiology practice. A 30-kW SP and a 30-kW high HF generator connected
      to a rotating anode x-ray tube were used for the study. Source-film distance,
      screen/film combination, and film processing were kept the same during the
      experiment. The mAs value yielding a similar film optical density of a stair step
      phantom, as assessed by a densitometer and a similar dose, as assessed by a solid
      state detector, was estimated for different kVp values. The ratio of the mAs used
      with the SP generator to the equivalent mAs used with the HF generator to produce
      similar film density or radiation dose was calculated. Subject contrast was
      measured for different kVp values as the relative difference in film optical
      density between two steps of the phantom. The waveform of the tube current was
      recorded for the two generators using an oscilloscope. Motion artifact was
      produced on a lateral radiograph of a canine tarsus using the two generators.
      Reproducibility was assessed by comparing the variances of film density
      measurements made on the central step of the phantom on 10 consecutive images
      produced with the two generators. mAs ratios (SP/HF) to obtain similar film
      optical density ranged from 2 (for 90kVp) to 2.5 (for 70 kVp), and mAs ratios to
      obtain similar radiation dose ranged from 1.2 (for 100 kVp) to 1.4 (for 70 kVp).
      Image contrast was slightly higher for the SP than for the HF generator. Current
      waveform for the SP generator was half-sinusoidal and it was almost continuous
      for the HF generator. Motion artifact appeared as blur for the HF generator and
      as several regularly placed images of the subject for the SP generator.
      Reproducibility was significantly better for the HF than for the SP generator (P
      = 0.047). It was concluded that the HF generator was approximately two times more
      efficient, had a better reproducibility, and produced images with a lower
      contrast than the SP generator. Motion artifact appears differently due to
      different current waveform.

PMID- 11954807
TI  - Mensuration of cervical vertebral ratios in Doberman pinschers and Great Danes.
AB  - Canine cervical vertebral instability is a complex syndrome involving cervical
      spinal cord compressive lesions. Doberman pinschers and Great Danes are the most
      commonly affected breeds. Measurements of vertebral canal diameter (VCD),
      vertebral body height (H), and vertebral body length (L) were made from C3-C7 in
      24 Doberman pinschers and 8 Great Danes by using digital and analog techniques.
      Significant differences between affected and unaffected sites were noted for
      Doberman pinschers at C6 (P = 0.039) and C7 (P = 0.027) using analog measurements
      of VCD/H, and Great Danes at C6 using analog (P = 0.041) and digital (P = 0.004)
      measurements of VCD/L. Cervical vertebral ratios have potential as a breed
      specific screening tool for cervical vertebral instability and warrant
      longitudinal studies.

PMID- 11954808
TI  - A newly recognized pattern of canine osteochondromatosis.
AB  - Clinicopathological findings are described for a unique skeletal pattern of
      osteochondromatosis (syn. multiple osteochondromas) in three crossbred littermate
      dogs. Multiple nonpainful bilaterally symmetric skeletal lesions arose from focal
      semiannular and annular areas of periosteal thickening on the cortical surface of
      the metaphyses and diaphyses of long bones. Flat bones of the skull were spared.
      In radiographs osteochondromas in different stages of evolution were apparent.
      Grossly there were smoothly contoured, nodular subperiosteal masses of dense
      fibrocartilaginous and osseous tissue that were continuous with and overlying
      apparently normal but thin trabeculae of cancellous bone. Cortical compacta was
      attenuated or absent beneath exostoses. In histologic sections of the cartilage
      capped exostoses a hyperplastic periosteum formed a focal semiannular or annular
      cap of proliferative hyaline cartilage tissue that underwent endochondral
      ossification and replacement by cancellous bone at its base. Intertrabecular
      spaces in the cancellous bone of exostoses were filled with fibro-osseous and
      hematopoietic tissue. A hereditary origin was suspected for the osteochondromas.
      Origin of some osteochondromas as semiannular or annular perturbations of the
      perichondrial ring of metaphyseal physes of long bones likely contributed to limb
      shortening and a pattern of billaterally symmetric angular limb deformities of
      all limbs as occurs in some children affected by osteochondromatosis.

PMID- 11954809
TI  - Multicentric lymphoma with intestinal involvement in a dog.
AB  - A 5-year-old, male German shepherd dog was evaluated for a 5-week history of
      vomiting, diarrhea, lethargy, and weight loss. In abdominal radiographs, there
      was an unusual corrugated appearance within a loop of intestine. Sonographically,
      this loop also had a similar corrugated appearance with alternating hyperechoic
      and hypoechoic bands. Lymph nodes within the abdomen and thorax were enlarged,
      and a thoracic mass was also detected. Ultrasound-guided fine-needle aspirates of
      the mesenteric lymph nodes were highly suggestive of lymphoma. After postmortem
      examination, a diagnosis of multicentric lymphoma with involvement of the
      gastrointestinal tract was made.

PMID- 11954810
TI  - Doppler echocardiography in the dog: measurement variability and reproducibility.
AB  - Serial Doppler echocardiographic examinations were carried out in random order on
      six boxer dogs, on 3 separate days, by two experienced Doppler
      echocardiographers, to assess measurement variability and reproducibility of 65
      parameters. Large numbers of parameters exhibited significant differences for
      each of the categories of intraobserver, interobserver, interday and
      interoperator. The coefficients of variation for all parameters measured ranged
      from 5.03 to 46.43%, but most were less than 20%. In general, least variation was
      found for the intraobserver category, and the best reproducibility for M-mode and
      left ventricular volumetric data. The worst reproducibility was found for
      tricuspid inflow and pulmonary venous flow measurements. The results of this
      study suggest differences greater than 20% for serial scans must be achieved to
      document genuine change, although the specific data should be consulted.
      Furthermore, variability and reproducibility are improved if a single experienced
      operator/observer acquires and measures serial scans.

PMID- 11954811
TI  - Evaluation of a novel doppler index of combined systolic and diastolic myocardial
      performance in Newfoundland dogs with familial prevalence of dilated
      cardiomyopathy.
AB  - A Doppler index of myocardial performance (IMP) has been recently proposed in
      human cardiology, which is calculated from the isovolumic contraction time (ICT),
      isovolumic relaxation time (IRT), and the ejection time (ET) using the following
      formula: (ICT+IRT)/ET. In this study, IMP was measured and evaluated in
      Newfoundland dogs categorized in four groups: Normal dogs (n = 31), dilated
      cardiomyopathy (DCM) (n = 34), depressed fractional shortening (dFS) (n = 27),
      and left ventricular enlargement (LVE) (n = 7). IMP was found to be independent
      of age, sex, body surface area, and the R-R interval in the Normal group. There
      were significant differences in IMP between the DCM group and the Normal and dFS
      groups (P < 0.05) and between Newfoundlands with overt vs. occult DCM. IMP is a
      Doppler index which appears to correlate with severity of disease and may be of
      use in the early diagnosis of affected dogs during screening for the presence of
      DCM.

PMID- 11954812
TI  - Ultrasonographic features of canine abdominal malignant histiocytosis.
AB  - Ultrasonographic features of canine abdominal malignant histiocytosis (MH) of 16
      dogs are reported. The most common finding was the presence of hypoechoic nodules
      in the spleen, some of which caused distortion of the splenic margin. The liver
      was the second-most commonly affected organ. Hepatic ultrasonographic features
      were highly variable, including hypoechoic, hyperechoic, or mixed echogenic
      lesions. Other common ultrasonographic abnormalities included hypoechoic nodules
      in the kidneys and mesenteric and medial iliac lymphadenopathy. The results of
      this study suggest that the ultrasonographic appearance of canine abdominal MH is
      nonspecific, and definitive diagnosis requires cytologic or histologic
      examination.

PMID- 11954813
TI  - Ultrasonographic assessment of metallic clip carotid anastomosis in sheep.
AB  - The aim of this study was to use ultrasonography to assess an experimental
      carotid arteriotomy followed by end-to-end anastomosis in the lamb. Animals were
      subjected to an experimental surgical procedure consisting of a right carotid
      artery arteriotomy and subsequent end-to-end anastomosis with nonpenetrating
      metallic clips. Left side arteries were used as control. Duplex ultrasonography
      was performed postoperatively to assess the evolution of the experimental
      anastomosis. Measurements were made on the right carotid to assess blood flow,
      peak systolic velocity, and end diastolic velocity, as well as arterial diameter.
      Animals were periodically checked during the six-month postoperative period.
      Operated vessels appeared normal during follow up, with pulsatile movements and
      size similar to non operated carotid arteries. A hyperechoic band, perpendicular
      to the vessel main axis, was seen on the longitudinal image in operated arteries,
      but not in the control group. This band corresponded to the anastomosis area,
      where the clips were positioned. No image suggestive of thrombosis was observed
      in any operated artery, and blood flow was maintained through the experiment.
      Finally, a decrease of vessel lumen diameter was evidenced at the level of the
      anastomosis during the first 30 postoperative days, but it was not present after
      the 90th postsurgical day. Duplex ultrasonography is a useful imaging technique
      for the assessment of anatomical details, acoustical properties of the vascular
      lumen, and study of the intimal surface and vessel wall in growing arteries
      subjected to surgery. Metallic clips as suturing technique in arterial
      anastomosis allow for normal vascular growth, as shown by the evolution of flow
      velocity and vessel diameter.

PMID- 11954815
TI  - Imaging of pheochromocytoma in 2 dogs using p-[18F] fluorobenzylguanidine.
AB  - p-[18F]Fluorobenzylguanidine ([18F]PFBG) is a norepinephrine analog that has been
      developed as a positron emission tomography (PET) imaging radiopharmaceutical.
      Myocardial sympathetic innervation, neuroendocrine structures, and tumors can be
      noninvasively imaged with [18F]PFBG. In this study, the uptake characteristics of
      [18F]PFBG were investigated in 2 dogs with a spontaneous pheochromocytoma. The
      extent of the pheochromocytoma was well documented in both dogs on the PET study.
      The standardized uptake values within the pheochromocytomas were greater than 25
      by 10 min, and were 37 and 50 by 45 min in each dog. A third dog that was
      suspected to have an adrenal mass was also studied. In this dog, the [18F]PFBG
      study was normal. Surgical exploration and adrenal biopsy confirmed the [15F]PFBG
      imaging findings in both dogs. In each dog, there was rapid blood-pool clearance
      (within 10 min after intravenous administration of the [18F]PFBG), with high
      uptake specific within the myocardium and adrenal medulla. The results indicate
      that [18F]PFBG may be useful for imaging canine pheochromocytomas and aid in
      differentiating adrenal masses.

PMID- 11954814
TI  - An infected hip prosthesis in a dog diagnosed with a 99mTc-ciprofloxacin
      (infecton) scan.
AB  - This case report describes the use of the 99mTc-labeled radiopharmaceutical
      ciprofloxacin (Infecton) in a case of hip prosthesis loosening in a dog. Serial
      planar radiographs were not conclusive, and culture of the synovial fluid was
      negative. Antibiotic treatment did not result in improvement of the lameness.
      Scintigraphy was performed with 99-Tc-Infecton, a tracer claimed to be specific
      for infection. Antibiotic treatment was interrupted 6 weeks prior to the
      examination. Planar and tomographic images at 3 h and at 24 h postinjection
      showed increased activity along the acetabulum and the proximal femoral bone
      surrounding the femoral prosthesis, indicating focal infection. Bacteriology
      performed after removal of the implant revealed Pseudomonas aeruginosa.

PMID- 11954816
TI  - Late complications of pelvic irradiation in 16 dogs.
AB  - When external beam radiation therapy is administered to the pelvis, normal
      tissues irradiated may include the colon, small intestine, urethra, bladder,
      bone, and spinal cord. The objectives of this retrospective study were to
      determine the incidence and severity of late radiation effects following pelvic
      irradiation in dogs and to identify factors that increase the risk of these
      effects. Medical records of all dogs treated with curative intent external beam
      radiation therapy to the pelvic region between 1993 and 1999 were reviewed.
      Patients with follow-up longer than 9 months or any patient that developed late
      complications earlier than 9 months were evaluated. Sixteen dogs met criteria for
      inclusion in this study. All dogs were treated with a 6-MV linear accelerator
      with bilaterally opposed beams. Diseases treated included transitional cell
      carcinoma of the bladder, transitional cell carcinoma of the prostate, and anal
      sac apocrine gland adenocarcinoma. Four dose/fractionation schemes were used:
      49.5 Gy in 3.3 Gy fractions, 54 Gy in 3.0 Gy fractions, 54 Gy in 2.7 Gy
      fractions, and 18 Gy intraoperative radiation therapy followed by 43 Gy external
      beam radiation therapy in 2.9 Gy fractions. Implantable chemotherapy in the form
      of an OPLA-Pt sponge was used in six dogs as a radiation potentiator. Colitis was
      the major late effect following pelvic irradiation, occurring in nine dogs (56%).
      Colitis was characterized as mild in three dogs, moderate in one dog, and severe
      in five dogs. Three of the dogs with severe effects suffered gastrointestinal
      perforation. All dogs with severe late effects received 3 or 3.3 Gy per fraction,
      and 80% received radiation potentiators. In the seven dogs that received 2.7 Gy
      or 2.9 Gy per fraction, late effects were classified as none (n = 5), mild
      colitis (n = 1), and moderate colitis (n = 1). Radiation therapy can be
      administered to the pelvic region with a minimal risk of late effects to the
      colon by giving smaller doses per fraction and avoiding systemic radiation
      potentiators.

PMID- 11954817
TI  - Images from the 2001 ACVR oral exam 2001: small animal diagnostics.

PMID- 11954818
TI  - Images from the 2001 ACVR certifying examination: large animal elective.

PMID- 11954819
TI  - Imaging of the canine and feline temporomandibular joint: a review.
AB  - The radiographic anatomy of the temporomandibular joint in the dog and cat is
      described in dorsoventral and oblique projections. The positioning for different
      oblique views in conventional radiography and technical details of computed
      tomography are reviewed. Typical radiographic features of craniomandibular
      osteopathy, dysplasia, luxation, subluxation, fractures, ankylosis, degenerative
      joint disease, infection, and neoplasia involving the temporomandibular joint are
      discussed.

PMID- 11954820
TI  - Anatomic reference for computed tomography of the head of the foal.
AB  - The purpose of this study was to produce an anatomic reference for computed
      tomography (CT) of the head of the foal for use by radiologists, clinicians, and
      veterinary students. The head from each of 2 foals, euthanized for reasons
      unrelated to head pathology, was removed and prepared for CT scanning. Using a
      third-generation CT scanner, 5-mm contiguous transverse images were acquired. The
      heads were then frozen and sectioned using a band saw, with the cuts matched as
      closely as possible to the CT slices. The anatomic sections were photographed and
      radiographed. The radiographs and anatomic photographs were digitized and matched
      with the corresponding CT image. Each CT image was compared with its
      corresponding radiographic and anatomic section to assist in the accurate
      identification of specific structures. Clinically relevant structures were
      identified and labeled in corresponding images (CT, anatomic slice, and
      radiograph of slice). Only structures identified in the CT image were labeled in
      1 of the other 2 images. Sagittal (reference) images of the horse's head were
      reconstructed from the transverse CT scans, and were used to indicate the level
      from which each of the transverse images was obtained. Corresponding labeled
      images were then formatted together with a legend for identification of specific
      anatomic structures.

PMID- 11954821
TI  - Surfactant therapy in infants and children: three years experience in a pediatric
      intensive care unit.
AB  - Despite the established success of surfactant application in neonates, the use of
      surfactant in older children is still a matter of discussion. We hypothesized
      that surfactant application in children with acute respiratory distress syndrome
      (ARDS) secondary to a pulmonary or systemic disease or after cardiac surgery
      improves pulmonary function. We also asked whether repeated treatment could
      further improve pulmonary function. To answer these questions, we measured
      oxygenation index (OI) and hypoxemia score after the first and after a second
      application of surfactant (50-100 mg/kg body wt) at least 24 h later. We enrolled
      19 children (older than 4 weeks) for a retrospective chart review study, and six
      of them underwent cardiac surgery. Demographic data were extracted. OI and
      hypoxemia score were estimated before and 2 and 24 h after surfactant
      application. Lung injury score was calculated before and 24 h after surfactant
      application. Outcome measures included survival, duration of mechanical
      ventilation, and pediatric ICU and hospital stay. The median patient age was 9.0
      (quarter percentile 3.7/25) months. The median weight was 8.4 (4.1/11.5) kg. The
      median lung injury score before the first surfactant application was 2.3
      (2.3/2.6). Hospital duration and pediatric ICU stay for all patients was 31.0
      (20.0/49.5) days and 27.0 (15.5/32.5) days, respectively. The duration of
      mechanical ventilation was 24.0 (18.5/31.0) days. The overall mortality was 53%.
      Twenty-four hours after the first surfactant application, pulmonary function
      significantly improved. The median OI was 14 (5.5/26) before and 7 (4.5/14.5) 24
      h after surfactant application (P= 0.027). The hypoxemia score was 91.7
      (69.9/154.2) before and 148.4 (99.2/167.6) 24 h after surfactant application (P =
      0.0026). Seven children received a second application, which did not further
      improve pulmonary function. The lung injury score was not influenced by either
      surfactant application. We conclude that a single surfactant application improves
      pulmonary function in children with ARDS. A second application of surfactant
      showed no further benefit. Outcome was not affected in our study population.

PMID- 11954822
TI  - A prospective study of inflammation markers in patients at risk of indirect acute
      lung injury.
AB  - Systemic inflammation triggered by insults like sepsis and acute pancreatitis may
      play a role in development of indirect acute lung injury (ALI) and acute
      respiratory distress syndrome (ARDS). Because little is known about the course of
      systemic inflammation on the days preceding diagnosis of ARDS, we prospectively
      monitored immune inflammatory status in 52 patients at risk and we assessed the
      presence of ALI and ARDS on day 7 after admission to the intensive care unit. On
      admission, serum interleukin (IL) 8, IL-6, and soluble IL-2 receptor
      concentrations were significantly higher in patients with subsequent ALI (n = 18)
      than in patients without ALI (n = 30). During a 4-day follow-up, IL-8 and IL-6
      levels of ALI patients remained high and those of non-ALI patients decreased.
      None of the markers discriminated ARDS patients (n = 9) from non-ARDS ALI
      patients (n = 9). Among 11 patients with acute pancreatitis, ALI patients had
      significantly higher IL-8, IL-6, and phagocyte CD11b expression levels than did
      non-ALI patients, whereas among 14 patients with massive transfusion, respective
      findings in ALI and non-ALI patients were comparable. Results give credence to
      the view that systemic inflammation plays a role in development of ALI triggered
      by pancreatitis, but not in that by massive transfusion. This finding, if
      confirmed in studies with sufficient statistical power, suggests that the
      patients with massive transfusion do not necessarily benefit from novel
      biotherapies aimed at altering the course of systemic inflammation.

PMID- 11954823
TI  - Effect of changes in surgical practice on the rate and detection of nosocomial
      infections: a prospective analysis.
AB  - The practice of surgery is being performed increasingly on an outpatient basis.
      How these changes have influenced the nosocomial infection rate and the ability
      of standard, Center for Disease Control (CDC)-designed surveillance techniques to
      detect these infections is unknown. The goal of this study was to determine
      whether recent changes in surgical care have led to an increased nosocomial
      infection rate based on number of discharges and whether current surveillance
      techniques are adequate to detect these complications. Data were collected
      prospectively on all nosocomial infections over a 1-year period on the general
      surgery, trauma, and transplant units at a university hospital, as independently
      observed by both the study team [surgical auditors (SA)] and CDC-trained
      infection control practitioners (ICP). The patient study group had a high acuity
      of illness (for 516 episodes of infection, mean APACHE II score of 15.4, 45%
      intensive care unit-bound, mortality of 16%). The overall infection rate per 100
      discharges was 23.8 for SA and 12.2 for ICP (P < 0.001 by chi2), higher than
      historical reports. SA detected significantly more surgical site infections,
      pneumonias, and non-Clostridium difficile-related gastrointestinal infections.
      These relative rates of detection, however, were similar to those described
      previously in prior studies using similar methodologies. The nosocomial infection
      rate in surgical patients, based on number of discharges, appears to be
      increasing, perhaps due to increased inpatient acuity of illness. Current
      epidemiological methods provide estimates of infection rates with effectiveness
      similar to that reported in previous epidemiological studies but fail to
      recognize many infections otherwise identified by surgeons dedicated to infection
      control.

PMID- 11954824
TI  - Platelet and leukocyte activation correlate with the severity of septic organ
      dysfunction.
AB  - This study was conducted to investigate the extent of platelet-leukocyte adhesion
      and platelet, monocyte, and neutrophil activation in septic patients and to
      analyze whether these variables correlate with the severity of sepsis. Forty
      seven patients consecutively admitted to the operative ICU of a University
      Medical Centre and 12 control patients prior to elective surgery were included in
      this prospective cohort study. Patients were evaluated daily for sepsis criteria
      and sepsis-associated organ failure assessment (SOFA) score was used to describe
      the extent of sepsis-associated organ failure. Indicators for cell activation
      (CD62P on platelets and CD11b on neutrophils and monocytes) and binding of
      platelets to neutrophils and monocytes were analyzed by flow cytometry. CD62P was
      increased on platelets from patients with sepsis compared with patients who did
      not have sepsis. Patients with sepsis also had higher CD11b expression on
      neutrophils and monocytes. Statistical analyses revealed a positive correlation
      between platelet CD62P expression and severity of sepsis, as well as a positive
      correlation between the SOFA score and CD11b on monocytes. No correlation was
      found between the SOFA score and CD11b on neutrophils. Higher values for platelet
      neutrophil adhesion were observed in patients with uncomplicated sepsis compared
      either with controls or to patients with septic shock. An inverse relation
      between severity of sepsis and extent of platelet-neutrophil adhesion was also
      obvious from correlation analysis. The results indicate that flow cytometry can
      be used to measure these parameters of cell activation in sepsis and that
      activation of platelets and monocytes as well as adhesion of platelets to
      neutrophils does play a role in the development of organ dysfunction.

PMID- 11954825
TI  - Acute hypoxemia in humans enhances the neutrophil inflammatory response.
AB  - The neutrophil (PMN) is regarded as a key component in the hyperinflammatory
      response known as the systemic inflammatory response syndrome. Acute respiratory
      distress syndrome (ARDS) and subsequent multiple organ failure (MOF) are related
      to the severity of this hyperinflammation. ICU patients who are at highest risk
      of developing MOF may have acute hypoxic events that complicate their hospital
      course. This study was undertaken to evaluate the effects of acute hypoxia and
      subsequent hypoxemia on circulating PMNs in human volunteers. Healthy subjects
      were exposed to a changing O2/N2 mixture until their O2 saturation (SaO2) reached
      a level of 68% saturation. These subjects were then exposed to room air and then
      returned to their baseline SaO2. PMNs were isolated from pre- and post-hypoxemic
      arterial blood samples and were then either stimulated with N-formyl-methionyl
      leucyl-phenylalanine (fMLP) or PMA alone, or they were primed with L-alpha
      phosphatidylcholine, beta-acetyl-gamma-O-alkyl (PAF) followed by fMLP activation.
      Reactive oxygen species generation as measured by superoxide anion production was
      enhanced in primed PMNs after hypoxemia. Protease degranulation as measured by
      elastase release was enhanced in both quiescent PMNs and primed PMNs after fMLP
      activation following the hypoxemic event. Adhesion molecule upregulation as
      measured by CD11b/CD18, however, was not significantly changed after hypoxemia.
      Apoptosis of quiescent PMNs was delayed after the hypoxemic event. TNFalpha, IL
      1, IL-6, and IL-8 cytokine levels were unchanged following hypoxemia. These
      results indicate that relevant acute hypoxemic events observed in the clinical
      setting enhance several PMN cytotoxic functions and suggest that a transient
      hypoxemic insult may promote hyperinflammation.

PMID- 11954826
TI  - Hyperoxia prolongs tumor necrosis factor-alpha-mediated activation of NF-kappaB:
      role of IkappaB kinase.
AB  - Hyperoxia and tumor necrosis factor-alpha (TNFalpha) are two canonical signals
      centrally involved in the pathophysiology of acute lung injury. We have attempted
      to elucidate the effects of these two stimuli on the signal transduction pathways
      of lung parenchymal cells. In cultured human lung epithelial cells, exposure to
      hyperoxia alone (95% oxygen) did not affect NF-kappaB activation or degradation
      of the NF-kappaB inhibitory protein, IkappaB alpha. Stimulation with TNFalpha
      alone increased NF-kappaB activation within 1 h and induced IkappaB alpha
      degradation within 0.5 h. After TNFalpha alone, NF-kappaB activation returned to
      baseline within 2 h and this corresponded with near complete IkappaB alpha
      resynthesis within 1 h of stimulation. In contrast, simultaneous exposure to
      hyperoxia and TNFalpha prolonged NF-kappaB activation up to 4 h, and IkappaB
      alpha degradation up to 2 h after stimulation. Hyperoxia did not affect TNFalpha
      mediated resynthesis of IkappaB alpha mRNA. Hyperoxia alone did not induce
      IkappaB kinase (IKK) activity, but significantly prolonged TNFalpha-mediated
      activation of IKK activity. Hyperoxia alone did not activate the intercellular
      adhesion molecule-1 (ICAM-1) promoter, but augmented TNFalpha-mediated activation
      of the ICAM-1 promoter. These data demonstrate that while hyperoxia alone does
      not affect activation of NF-kappaB, hyperoxia prolongs TNFalpha-mediated
      activation of NF-kappaB. The mechanism of this effect involves, in part,
      prolonged degradation of IkappaB alpha resulting from prolonged activation of
      IKK.

PMID- 11954827
TI  - Kupffer cells protect liver from ischemia-reperfusion injury by an inducible
      nitric oxide synthase-dependent mechanism.
AB  - The aim of this study was to investigate the role of nitric oxide (NO) in rat
      hepatic ischemia-reperfusion (I/R) injury. Animals were divided into four groups:
      Group I, control; Group II, gadolinium chloride (GdCl3), a Kupffer cell depleting
      agent, pretreated; Group III, S-methylisothiourea (SMT), a potent inducible NO
      synthase (iNOS) inhibitor, pretreated; Group IV, pretreated with SMT, then
      treated with S-Nitroso-N-acetylpenicillamine (SNAP), a NO donor, after ischemia.
      Sprague-Dawley rats underwent left lateral and median lobe ischemia for 60 min
      and reperfusion for 120 min. The left lateral and median lobes were used as
      ischemic lobes, and the right lateral lobe in the same rat was used as a control
      lobe. The total NOS (tNOS), iNOS, constitutive NOS (cNOS) activity, and liver
      protein were determined. The liver tissue malonaldehyde (MDA) level was measured
      as an index of lipid peroxidation. Liver histology was also examined. The liver
      tNOS activity in ischemic lobes of Group I, II, III, and IV was increased by
      214%, 86%, 61%, and 45%, respectively. The increase in tNOS activity is mainly
      due to the induction of iNOS activity in the ischemic lobes of rat liver. GdCl3
      significantly decreased the tNOS by 66% in the ischemic lobes. GdCl3
      significantly increased MDA by 39% in the ischemic lobes. SMT significantly
      decreased tNOS and iNOS activity by 66% and 85% in ischemic lobes. SMT increased
      MDA by 67% in the ischemic lobes. SMT + SNAP treatment increased iNOS activity by
      117% in the ischemic lobes in comparison with the ischemic lobes of the SMT
      group. SMT + SNAP treatment decreased MDA by 39% in the ischemic lobes. SMT +
      SNAP treatment also decreased the sinusoidal congestion and spotty necrosis of
      hepatocytes in the ischemic lobes. iNOS immunostaining showed an obvious increase
      in sinusodial area of the ischemic lobes where most Kupffer cells were
      interspersed. In conclusion, in this model of liver I/R injury, I/R increased the
      activity of tNOS and iNOS, but not the cNOS activity. Kupffer cells might be the
      major source of the induction of iNOS activity. The iNOS specific inhibitor SMT
      increased the lipid peroxidation and the tissue damage in hepatic I/R injury. On
      the contrary, the NO donor SNAP increased the activity of iNOS and decreased the
      hepatic injury in this study. Kupffer cells could protect liver from I/R injury
      by an iNOS-dependent mechanism, thus NO production has a beneficial role in
      hepatic IR injury.

PMID- 11954828
TI  - Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient
      mice.
AB  - Sepsis is associated with a widespread production of proinflammatory cytokines
      and various oxidant species. Activation of the enzyme poly(ADP-ribose) polymerase
      (PARP) has been shown to contribute to cell necrosis and organ failure in various
      diseases associated with inflammation and reperfusion injury. The aim of the
      current study was to elucidate the role of PARP activation in the multiple organ
      dysfunction complicating sepsis in a murine model of polymicrobial sepsis induced
      by cecal ligation and puncture (CLP). Mice genetically deficient in PARP (PARP-/
      ) and their wild-type littermates (PARP+/+) were subjected to CLP. After 12 and
      24 h, the proinflammatory cytokines TNF-alpha and IL-6, as well as the anti
      inflammatory cytokine IL-10, and nitrite/nitrate were measured in plasma samples.
      Organs were harvested for the measurement of myeloperoxidase (MPO) and
      malondialdehyde (MDA) levels, and immunohistochemical staining for nitrotyrosine
      and poly(ADP ribose) was performed in gut sections. PARP-/- mice, and their wild
      type littermate showed a similar time-dependent increase in plasma
      nitrite/nitrate and in gut and lung MDA content, as well as the presence of
      nitrotyrosine in the gut. In contrast to wild-type mice showing a PARP activation
      in the gut, PARP-/- mice had no staining for poly(ADP ribose). PARP-/- mice had
      significantly lower plasma levels of TNF-alpha, IL-6, and IL-10, and they
      exhibited a reduced degree of organ inflammation, indicated by decreased MPO
      activity in the gut and lung. These effects were associated with a significant
      improvement in the survival of CLP in PARP-/- mice. Thus, PARP activation has an
      important role in systemic inflammation and organ damage in the present model of
      polymicrobial septic shock.

PMID- 11954829
TI  - The time course of cardiac NF-kappaB activation and TNF-alpha secretion by
      cardiac myocytes after burn injury: contribution to burn-related cardiac
      contractile dysfunction.
AB  - Previous studies have suggested that cardiac synthesis of TNF-alpha contributes
      to myocardial dysfunction in several models of trauma, sepsis and ischemia.
      Therefore, it is likely that myocyte secretion of TNF-alpha occurs early after
      major burn trauma, contributing to progressive cardiac contractile dysfunction
      that is characteristic of thermal injury. This study examined the time course of
      nuclear translocation of the transcription factor NF-kappaB, the time course of
      TNF-alpha secretion by cardiomyocytes after burn trauma, and the development of
      cardiac contractile defects. Rats were given burn injury over 40% TBSA (sham
      burns included for controls), and fluid resuscitation included lactated Ringer's
      solution, 4 mL/kg/%burn. Subsets of rats were sacrificed at several times
      postburn (1, 2, 4, 8, 12, 18 and 24 h), hearts were harvested to prepare
      cardiomyocytes (N = 4 rats/group/time period), to prepare nuclear fractions to
      measure burn-induced NF-kappaB activation (N = 3-4 rats/group/time period), or to
      examine the time course of postburn cardiac contractile dysfunction (N = 6-7
      rats/group/time period). Despite aggressive fluid resuscitation, burn trauma
      activated NF-kappaB 4 h postburn, and this activation persisted over the 24 h
      study period. In addition, burn trauma produced a time-related increase in TNF
      alpha secretion by cardiac myocytes with cytokine secretion evident 1 h postburn.
      Cardiac dysfunction occurred 8 h postburn and persisted over the 24 h study
      period. Administration of a strategy designed to inhibit NF-kappaB activation (N
      acetyl-leucinyl-leucinyl-norleucinal, ALLN, 50 mg/kg, in additional groups of
      burn rats) inhibited TNF-alpha secretion by cardiac myocytes and improved
      myocardial function. This study confirms that burn trauma activates myocardial NF
      kappaB and promotes cardiomyocyte secretion of TNF-alpha. This inflammatory
      cascade preceded the appearance of cardiac dysfunction, suggesting that cardiac
      myocyte derived TNF-alpha contributes, in part, to postburn cardiac contractile
      deficits.

PMID- 11954830
TI  - Characterization of a murine model of endotoxin-induced acute lung injury.
AB  - Endotoxin-induced microvascular lung injury in mice is a commonly used
      experimental model of the acute respiratory distress syndrome (ARDS). The present
      paper aimed to characterize this popular model in a comprehensive and systematic
      fashion. Male C57bl/6 mice (n = 5) were administered an LD55 dose of E. coli
      endotoxin (15 mg/kg, i.p.), and lungs were harvested at several time points and
      evaluated for injury as well as for expression of a variety of inflammatory
      mediators. Endotoxin induced many features characteristic of acute microvascular
      lung injury. These included early (1-2 h) expression of inflammatory mediators
      (IL-1alpha, IL-1beta, IL-4, IL-6, IL-10, TNF-alpha, interferon-alpha, interferon
      gamma, and MCP-1) and leukocyte accumulation in lung tissue (lung myeloperoxidase
      activity 18.5 +/- 7.8 U/g tissue, P < 0.05), followed by pulmonary edema (lung
      water content index 17.4% +/- 2.5%, P < 0.05) and mortality. Histopathological
      evaluation of lung tissue was compatible with these findings. The
      characterization of this murine model of endotoxin-induced microvascular injury
      will facilitate its utilization in ARDS research.

PMID- 11954831
TI  - PDTC and Mg132, inhibitors of NF-kappaB, block endotoxin induced vasodilation of
      isolated rat skeletal muscle arterioles.
AB  - NF-kappaB is a ubiquitous transcription factor that mediates the inflammatory
      response. Inhibition of NF-kappaB may be of potential therapeutic benefit in the
      treatment of septic shock. The antioxidant pyrrolidine dithiocarbamate (PDTC) has
      been shown in previous work to selectively inhibit NF-kappaB activation.
      Likewise, the proteasome inhibitor MG132 inhibits NF-kappaB formation and
      degradation of its inhibitor I-kappaB. The goal of this study was to determine if
      PDTC and MG-132 could inhibit resistance arteriole vasodilation in response to
      endotoxin and to determine PDTC's site of action in our isolated vessel
      preparation. Male Sprague-Dawley rats were given an intraperitoneal injection of
      PDTC, an intravenous injection of MG132, or a sham injection. First-order
      cremasteric arterioles were isolated, cannulated, and pressurized. A segment of
      thoracic aorta was then placed in series with the microvascular preparation.
      Vessels were allowed to achieve spontaneous myogenic tone in a bath of buffer
      over 1 h (t = 0). Internal vessel diameters were measured and the response to
      endotoxin (ET) or continued infusion of buffer was measured over 1 h (t = 60).
      Group 1 (n = 7) was a time-control group. Group 2 (n = 7) was exposed to ET only,
      Group 3 (n = 5) received PDTC and was exposed to ET, Group 4 (n = 5) received
      PDTC only, Group 5 (n = 4) received MG132 only, and Group 6 (n = 5) received
      MG132 and was exposed to ET. To determine the site of action of PDTC, a segment
      of aorta from an animal treated with PDTC was placed in series with a cremasteric
      arteriole from an animal receiving a sham injection. The preparation was then
      exposed to ET, and this is Group 7 (n = 4). Group 8 (n = 4) received ET and was
      composed of thoracic aorta from an animal receiving a sham injection and a
      cremasteric arteriole from a PDTC-treated animal. Spontaneous tone was similar in
      the eight groups at the end of the equilibration period (t = 0). After 1 h (t =
      60), Group 2 (vessels exposed to ET only) had significantly less tone (26.1%+/
      2.6%; P < 0.01) than Group 1 (39.0%+/-2.4%), Group 3 (39.3%+/-3.1%), Group 4
      (41.2%+/-1.6%), Group 5 (39.2%+/-2.9%), Group 6 (41.0%+/-2.7%), Group 7 (45.1%+/
      6.5%), and Group 8 (41.1%+/-4.5%). We conclude that PDTC and MG132, inhibitors of
      NF-kappaB, block ET-induced vasodilation in isolated rat skeletal muscle
      arterioles. PDTC has effects at both the level of the aortic segment as well as
      the resistance arteriole. Inhibitors of NF-kappaB may potentially be of
      therapeutic benefit in the treatment of septic shock.

PMID- 11954832
TI  - Taurolidine attenuates the hemodynamic and respiratory changes associated with
      endotoxemia.
AB  - The purpose of this study was to determine if prereatment with taurolidine, a
      known anti-endotoxin agent, would attenuate the hemodynamic and respiratory
      responses associated with endotoxin induced lung injury in a large animal model
      in a randomized controlled study under license from the Department of Health. All
      animals underwent a general anesthetic. Vascular catheters were placed in the
      femoral artery and in the femoral vein. A Swan-Ganz Catheter was inserted for
      measurement of pulmonary artery pressure. Animals were randomized into three
      groups: Control, with measurements taken at baseline and half hourly up to 90
      min; Endotoxin, receiving 5microg/Kg E. coli endotoxin intravenously after
      baseline measurements; and Endotoxin + Taurolidine, receiving 5g of taurolidine
      via intraperitoneal infusion 1 h before endotoxin administration. Main outcome
      measures were mean systemic arterial pressure (MAP), mean pulmonary arterial
      pressure (MPAP), arterial oxygen tension (pO2), serum endotoxin concentration,
      and pulmonary myeloperoxidase. Endotoxin induced a significant lung injury
      characterized by an increase in pulmonary artery pressure, hypoxia, and systemic
      hypotension. Pretreatment with intraperitoneal taurolidine significantly
      attenuated these hemodynamic and respiratory changes. Serum endotoxin
      concentration was also significantly reduced as was lung myeloperoxidase. The
      data suggest that taurolidine may have a therapeutic role in preventing the lung
      injury seen in endotoxemia.

PMID- 11954833
TI  - Splenectomy ablates endotoxin-induced IFNgamma response in rats.
AB  - The mechanism of liver injury in endotoxemia is unclear. Previous studies have
      shown that splenectomy protects the liver from endotoxin-induced injury. The
      purpose of this study was to determine the relationship of TNFalpha and IFNgamma
      release and endotoxin-induced liver injury in splenectomized and
      nonsplenectomized rats. Splenectomized and nonsplenectomized (Sham) rats with
      chronic catheters in the aorta and inferior vena cava (IVC) were parenterally
      infused with 10 to 5000 microg/kg endotoxin. TNFalpha, IFNgamma, and alanine
      aminotransferase (ALT), a marker of hepatocellular damage, were measured in
      aortic blood. Compared to sham controls, splenectomized animals demonstrated
      significantly reduced endotoxin-induced ALT concentrations at endotoxin doses >10
      microg/kg. Peak endotoxin-induced TNFalpha concentrations were not significantly
      different between the splenectomized and sham groups. In contrast, peak endotoxin
      induced IFNgamma concentrations were significantly decreased in the
      splenectomized group. These data suggest a relationship between endotoxin-induced
      IFNgamma and liver injury. We speculate that the spleen contributes to the
      endotoxin-induced liver injury by modulating release of IFNgamma.

PMID- 11954834
TI  - LPS-induced imbalanced expression of hepatic vascular stress genes in cirrhosis:
      possible mechanism of increased susceptibility to endotoxemia.
AB  - Cirrhosis predisposes the liver to secondary stresses such as endotoxemia
      possibly via dysregulation of the hepatic portal circulation secondary to
      imbalanced upregulation of vascular stress genes. In this study we determined the
      effect of cirrhosis on hepatic vasoregulatory gene expression in response to
      endotoxin (LPS, i.p., 1 mg/kg). Cirrhosis was induced by bile duct ligation (BDL)
      for 21 days in male Sprague-Dawley rats. Plasma and liver samples were taken 6 h
      following an injection of LPS for alanine aminotransferase (ALT) assays and RT
      PCR analysis of mRNA levels for genes of interest: endothelin (ET-1), its
      receptors ET(A) and ET(B), endothelial nitric oxide synthase (eNOS), inducible
      NOS (iNOS), and heme oxygenase-1 (HO-1). ALT release increased by 5.5-fold in the
      BDL animals and 9.9-fold in BDL + LPS compared to sham. ET-1 mRNA was increased
      by either LPS or BDL treatment alone and increased significantly more in BDL +
      LPS compared to sham + LPS. mRNA levels for ET(B) receptors showed no change,
      whereas ETA transcripts decreased in BDL animals compared to sham, with no
      significant difference between the saline and LPS treatment groups. The resultant
      increased ratio of ET(B) over ET(A) in BDL animals was reflected functionally in
      the portal pressure responses to ET(A) and ET(B) agonists ET-1 and IRL-1620 (a
      specific ETB receptor agonist). The pressor response to ET-1 was attenuated,
      while the response to IRL-1620 was similar in BDL and sham. eNOS mRNA levels did
      not increase in response to either BDL or LPS or a combination of both compared
      to sham. The increase in iNOS mRNA was attenuated in BDL + LPS compared to sham +
      LPS. HO-1 expression increased significantly in sham + LPS, but failed to
      increase in BDL + LPS. Taken collectively, significantly greater induction of the
      constrictor ET-1 over the dilation forces (i.e., eNOS, iNOS, and HO-1) was
      observed in BDL + LPS. This suggests a compromised ability of the cirrhotic liver
      to upregulate sufficient dilatory forces to counterbalance the constrictive
      effect of ET-1 upon a secondary insult of endotoxemia. These results may partly
      explain the increased susceptibility of cirrhotic livers to injury as a result of
      endotoxemia.

PMID- 11954835
TI  - Induction of early inflammatory gene expression in a murine model of
      nonresuscitated, fixed-volume hemorrhage.
AB  - The etiology of many end-organ problems associated with hemorrhage has been
      attributed to the inflammatory response to hemorrhage. In a murine model of
      nonresuscitated, fixed-volume hemorrhage, we sought to elucidate the role that
      hemorrhagic insult alone plays in the generation of the early inflammatory
      cascade. Differences could be appreciated as early as 1 h post-hemorrhage, with
      consistent differences detected by 3 h in all of the major cytokine genes
      studied. Significant upregulation of IL-1beta , IL-6, TNF-alpha, and IL-10 mRNA
      expression was observed in both the liver and lung samples of mice subjected to
      fixed-volume hemorrhage when compared with sham-hemorrhaged mice. The
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthetase (iNOS) genes also
      were upregulated in the livers and lungs of hemorrhaged mice. Finally, expression
      of the genes that encode the Toll-like receptors (TLR)-2 and -4 was increased by
      hemorrhage. Taken collectively, these data demonstrate that the initial
      inflammatory cascade associated with hemorrhage occurs within hours after the
      initial hemorrhagic event, and can be associated with significant modulation of
      expression of key pro- and anti-inflammatory cytokine, enzyme, and TLR genes,
      suggesting that these may be possible new therapeutic targets.

PMID- 11954836
TI  - The significance of changes in high mobility group-1 protein mRNA expression in
      rats after thermal injury.
AB  - There has been a widespread impression that tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1beta (IL-1beta) mediate the toxicity of high doses of
      lipopolysaccharide (LPS, endotoxin) and are key factors in septic shock. However,
      the clinical efficacy of treatment with antagonists of TNF-alpha and IL-1beta is
      still controversial, suggesting that mediators other than TNF-alpha and IL-1beta
      might contribute causally to endotoxin-induced death. Recent studies implicated
      high mobility group-1 (HMG-1) protein as a late mediator of endotoxin lethality
      in mice. However, the role of HMG-1 in mediating multiple organ damage
      associating trauma has not been studied. This study was designed to investigate
      changes in HMG-1 gene expression in vital organs, and its potential role in
      mediating multiple organ damage following major burns. Wistar rats were subjected
      to a 35 percent full-thickness thermal injury, and randomly divided into three
      groups as follows: normal controls (n = 7), thermal injury (n = 24), and
      recombinant bactericidal/permeability-increasing protein (rBPI21) treatment (n =
      12). Tissue samples from liver and lungs were collected to measure tissue
      endotoxin levels and HMG-1 mRNA expression. In addition, blood samples were
      obtained for measurement of organ function parameters. Our data demonstrated a
      significant increase in HMG-1 gene expression in tissues at 24 h postburn, which
      remained markedly elevated up to 72 h after thermal injury (P< 0.05-0.01).
      Treatment with rBPI21 could significantly decrease tissue HMG-1 mRNA expression
      in the liver and lung (P < 0.01). In addition, there were high positive
      correlations between hepatic HMG-1 mRNA and serum aminoleucine transferase (ALT)
      and aspartate aminotransferase (AST) levels, and also between pulmonary HMG-1
      mRNA and myeloperoxidase activities (P < 0.05-0.01). Taken together, these
      findings indicate that thermal injury per se can markedly enhance HMG-1 gene
      expression in various organs. Up-regulation of HMG-1 expression may be involved
      in the pathogenesis of endogenous endotoxin-mediated multiple organ damage
      secondary to major burns.

PMID- 11954837
TI  - Role of prostacyclin on microcirculation in endotoxin-induced gastroprotection in
      rats: a microdialysis study.
AB  - Numerous mechanisms relating to lipopolysaccharide- (LPS) induced
      gastroprotection have been proposed. The prostaglandin (PG) system is a promising
      candidate that has received considerable attention. However, the role of
      prostacyclin (PGI2) remains unclear. Adult, male Sprague-Dawley rats were divided
      into four groups: (1) control, n = 6; (2) LPS (LPS, 10 mg/kg, i.v.), n = 7; (3)
      LPS + indomethacin (Indo) (LPS, 10 mg/kg and indomethacin 5 mg/kg, i.v.), n = 7;
      and (4) Indo (indomethacin 5 mg/kg, i.v.), n = 7. Additionally, gastric
      microcirculation was investigated using in vivo microscopy. Tissue
      malondialdehyde (MDA) and glutathione levels were measured at the conclusion of
      the experiment. Specifically, microdialysis was used to measure the 6-keto
      PGF1alpha, a stable metabolite of PGI2, while flow cytometry was used to measure
      the CD11b/CD18 expression of circulating neutrophils. Compared with LPS alone,
      LPS with Indo significantly impaired gastric microcirculation and systemic
      hemodynamics. LPS-induced gastroprotection was lost, as evidenced by the
      increased adherent leukocyte count, decreased flow velocity in the post-capillary
      venules, and increased tissue MDA production. Meanwhile, the luminal glucose and
      protein contents that comprised the gastric mucosa injury index were
      significantly increased. These effects of Indo are directly associated with the
      levels of PGI2 in gastric tissue, which increased with LPS alone and
      significantly decreased with a combination of LPS and Indo. This work
      demonstrates that PGI2 contributes to LPS-induced gastroprotection.

PMID- 11954839
TI  - Modified and classic acromioplasty for impingement of the shoulder.
AB  - We compared the results of modified and classic anterior acromioplasty in order
      to identify the significance of the resected acromion. Fifty patients with
      shoulder impingement syndrome resistant to conservative therapy underwent
      surgical treatment. We treated 30 patients with classic Neer acromioplasty (group
      1), and 20 patients with modified Neer acromioplasty (group 2). The patients were
      assessed according to pain and shoulder movement. Excellent or good results were
      achieved in 28/30 patients in group I and 19/20 patients in group 2. The results
      indicate that both surgical techniques are effective procedures in the treatment
      of shoulder impingement syndrome, and the type of bone resection does not
      influence the clinical outcome.

PMID- 11954838
TI  - Deferoxamine and hespan complex as a resuscitative adjuvant in hemorrhagic shock
      rat model.
AB  - The optimal type and amount of fluid for resuscitation of injured patients in
      hemorrhagic hypovolemic shock remains controversial. Use of deferoxamine, an iron
      chelator and oxygen-free radical scavenger, and hespan (hydroxyethyl starch), a
      colloid plasma expander, was evaluated in a rat hemorrhagic shock model. Eighty
      Sprague-Dawley male rats were utilized in four experiments. In these rats, bi
      femoral cutdowns were performed for blood withdrawal, resuscitation, blood
      sampling, and continuous blood pressure monitoring. All rats, except control
      (with bilateral cutdown only), were bled and maintained at 40 mmHg for 90 min.
      The shed blood was returned and animals were resuscitated. One hour later, 2
      mg/kg lidocaine was injected and blood samples were taken at 10, 15, 30, and 60
      min for evaluation of lidocaine derivative monoethylglycinexylidide (MEGX) by
      fluorescent polarization immunoassay. In experiment 1 (n = 31), resuscitation
      with different volumes of Ringer's lactate (7.5 mL, 15.0 mL, and 30.0 mL/kg) was
      compared and 7.5 mL/kg LR was most beneficial. In experiment 2 (n = 22),
      resuscitation with three doses of Hespan (3.75 mL, 7.5 mL, and 15 mL/kg) was
      compared. A dose of 15 mL/kg significantly improved the liver function. In
      experiment 3 (n = 15), resuscitations with two doses of deferoxamine (30 mg and
      100 mg/kg) were compared. A dose of 100 mg/kg significantly improved the liver
      function. In experiment 4 (n = 12), a combination of deferoxamine (100 mg/kg) and
      Hespan (3.75 and 7.5 mL) was used. Deferoxamine (100 mg/kg) complexed with 7.5 mL
      of Hespan was found the most beneficial resuscitation. This conjugate could be a
      choice as a resuscitative adjuvant in hypovolemic shock without any side effects.

PMID- 11954840
TI  - Internal fixation of valgus-impacted humeral head fractures using the screw
      wiring technique.
AB  - Between February 1996 and July 2000 eight patients (ages 35-74 years) with nine
      severely impacted humeral head fractures were operated on with the aim of
      preserving the humeral heads. Patients were treated surgically with open
      reduction, autologous bone grafting, and internal fixation with a screw-wiring
      technique. There were no complications and all patients were satisfied with the
      results. After 10-63 months there was no evidence of nonunion, arthritis,
      avascular necrosis, or loosening of implants. The mean Constant score was 83 (66
      97) points. Results of this study support the observation that four-part valgus
      impacted humeral head fractures without significant lateral displacement have a
      low incidence of avascular necrosis.

PMID- 11954841
TI  - Closed retrograde nailing of pathological humeral fractures.
AB  - We treated 19 patients with 21 pathological humeral fractures secondary to
      metastatic disease. All patients were stabilized using retrograde Ender's nails.
      Open reduction was required in one patient and mean operative time was 40 min
      (range 30-65 min). All patients retained satisfactory elbow and shoulder function
      while 16 patients reported good pain relief. Functional recovery was rated as
      good in 15 patients, fair in three, and poor in one. In our experience the
      retrograde technique using Ender's nails provides secure stabilization with
      minimal morbidity, minimal blood loss, and short operative time, and is well
      suited for this category of patients.

PMID- 11954842
TI  - Primary bone grafting does not improve the results in severely displaced distal
      radius fractures.
AB  - We prospectively randomised 45 patients ages 20-70 years with distal radius
      fractures of Older type III and IV to one of two treatment groups. One group was
      treated with closed reduction, primary bone grafting, and external fixation for 3
      weeks, followed by a plaster cast that allowed volar flexion, for an additional 3
      weeks. The other group was treated with closed reduction and external fixation
      for 6 weeks. The functional and radiographic results were evaluated. There was no
      difference between the two groups in either clinical or radiographic outcome. We
      do not recommend external fixation and primary bone grafting as a routine method
      in these fractures.

PMID- 11954843
TI  - Surgical release of de Quervain's stenosing tenosynovitis postpartum: can it
      wait?
AB  - We compared the efficacy of conservative management of de Quervain's disease in
      30 women postpartum (group 1) and 30 nonpregnant women (group 2). All patients
      underwent conservative management consisting of 2 weeks of splinting of the
      affected wrist, followed by physiotherapy and antiinflammatory drugs (NSAIDs).
      Clinical evaluation was performed using a functional score and the visual
      analogue scale (VAS) of Scott-Huskinson at entry to the study, 1 month later, and
      at a follow-up of 6 months. Conservative management gave good results in patients
      in group 1. At the 6-month follow-up a significant difference between the two
      groups on pain and function was evident. Only one patient in group 1 versus 25
      patients in group 2 underwent surgery because of failure of conservative
      management.

PMID- 11954844
TI  - Treatment of bone and soft tissue sarcomas of the hand and wrist.
AB  - We studied 13 consecutive patients with bone and soft tissue sarcomas of the hand
      and wrist. Chondrosarcoma, Ewing's sarcoma, synovial sarcoma and epithelioid
      sarcoma were the most frequent histological diagnoses. Limb-sparing surgery was
      performed in ten patients but eventually three patients required an amputation.
      Surgical margins were wide in nine patients and marginal in four. Adjuvant
      therapy for nine patients consisted of chemotherapy in five and chemotherapy with
      radiation in four. Local recurrence occurred in two patients with epithelioid
      sarcoma. There was no significant relationship between surgical margin and local
      recurrence. Distant metastasis occurred in four patients. The 5-year survival
      rate was 66%. The mean functional score was 87%. Our study indicates that
      treatment consisting of resection of these tumours with either a wide margin or a
      marginal margin followed by adjuvant radiation appeared to be safe and resulted
      in an acceptable degree of limb function except in the patients with epithelioid
      sarcoma.

PMID- 11954845
TI  - Quality of life in osteogenesis imperfecta.
AB  - The purpose of this study was to quantify the physical and mental health of a
      diverse adult cohort of patients with osteogenesis imperfecta (OI) utilizing a
      validated health self-assessment questionnaire (SF-36). In addition, a specific
      demographic questionnaire and a functional questionnaire were utilized to assess
      more specifically the physical limitations imposed by osteogenesis imperfecta in
      adulthood. The results of the SF-36 revealed significantly lower physical
      function scores compared to the U.S. adult norms. However, the SF-36 mental
      component scores were equal to the U.S. adult norms. The demographic
      questionnaire revealed high levels of educational achievement, as well as
      employment, despite significant physical impairments. The functional
      questionnaire clearly demonstrated limitations mostly related to ambulation.

PMID- 11954846
TI  - Core decompression in early stages of femoral head osteonecrosis--an MRI
      controlled study.
AB  - We treated 45 hips with idiopathic necrosis of the femoral head stages I-III with
      core decompression. Average age of patients was 41 (27-68) years and average
      follow-up 68.9 (31-120) months. In 30 hip joints in stage I, 29 showed no
      radiographic progression and a complete remission of the changes consistent with
      necrosis on MRI at the last follow-up. In 27 patients the clinical result based
      on the Harris Hip Score (HHS) assessment--was excellent (average HHS 91.9
      points). Of nine hips in stage II, four had received a total hip arthroplasty,
      one had deteriorated to stage IV, and four were still classified as stage II
      (average HHS 95 points). Of six hips in stage III, three had received a total hip
      arthroplasty and three had deteriorated to stage IV (average HHS 73 points).

PMID- 11954847
TI  - Femoral revision using the Wagner stem: results at 2-9 years.
AB  - We followed 39 patients with 40 revision hip arthroplasties using the Wagner
      stem. Mean follow-up was 65 (29-108) months. There were 12 intraoperative
      proximal femoral fractures, which all united, five postoperative dislocations not
      related to subsidence, and two loose stems that were revised. Clinical
      improvement was best for pain. Once the stem was osteointegrated the clinical and
      radiological result remained stable for up to 9 years.

PMID- 11954848
TI  - The outcome of perioperative wound infection after total hip and knee
      arthroplasty.
AB  - Forty-one consecutive patients with primary knee arthroplasty and 37 with primary
      hip arthroplasty, all with perioperative wound infections, were followed for 50
      (12-130) months. Staphylococci (coagulase negative and positive) accounted for
      74% of wound infections. Mixed organisms accounted for 10%. Prosthetic infections
      developed in eight patients and aseptic loosening in three patients. All the
      prosthetic infections developed within 6 months of the primary surgery. Organisms
      responsible for superficial infections were responsible for prosthetic infection
      in five patients; no organisms were isolated in the remaining three patients. The
      presence or absence of wound dehiscence, wound haematoma, and postoperative
      pyrexia did not predict the development of deep sepsis; however, the presence of
      wound discharge was a significant risk factor.

PMID- 11954850
TI  - Comparison of two total knee prostheses on the incidence of patella clunk
      syndrome.
AB  - The patella clunk syndrome is not an uncommon complication, particularly after
      posterior-stabilized (PS) total knee arthroplasty. The present study was a
      consecutive unselected series comparing the incidence of the patella clunk
      syndrome amongst two comparable groups of elderly patients with knee arthritis
      implanted with the Insall-Burstein (IB II) total knee system and the newer NexGen
      Legacy total knee prosthesis. While 7.5% of patients in the PS IB II group
      developed patella clunk syndrome, none occurred in the NexGen group (P=0.05). We
      believe the difference is due mainly to a change in the design of the prosthesis,
      especially the more posterior intercondylar box and femoral cam of the NexGen
      femoral component.

PMID- 11954849
TI  - Thromboembolic complications after total hip replacement.
AB  - We conducted a retrospective analysis of 1,640 consecutive patients undergoing
      total hip replacement between 1990 and 1997 under general anesthesia and
      receiving three different prophylactic regimens. The thromboembolic prophylaxis
      consisted of low-dose unfractioned heparin (UFH), low-molecular-weight heparin
      (LMWH), or indobufen (INDO). Postoperatively, occurrence of symptomatic deep vein
      thrombosis (DVT) or pulmonary embolism (PE) was recorded during the first 30 days
      after surgery and at a routine follow-up visit. Symptomatic DVT was diagnosed in
      16 patients (0.9%), while PE occurred in eight patients (0.5%). Patients
      receiving UFH showed a higher incidence of symptomatic DVT (3.6%) than those
      patients receiving either LMWH (1.3%) or INDO (0.3%), with an odds ratio for
      developing symptomatic DVT when receiving UFH versus other treatments of 6.05
      (95% confidence intervals [CI95%]: 3.63-10.07) (P=0.001). On the other hand, the
      diagnosis of PE was more frequently seen in patients receiving cemented hip
      arthroplasty (2.4%) than in patients receiving uncemented hip arthroplasty
      (0.34%), with an odds ratio of 3.185 (CI95%: 2.01-5.02)(P=0.05).

PMID- 11954851
TI  - Retrograde flexible intramedullary nailing in children's femoral fractures.
AB  - We treated 31 femoral shaft fractures in 28 children with a mean age of 6.7 (5
      10) years with retrograde flexible intramedullary nailing. There were 16 isolated
      fractures, while 12 children had associated injuries. The average time for union
      was 10.5 weeks and there were no delayed unions. There was one broken nail
      requiring change of treatment, but no infection or refractures. At follow-up
      after a mean time lapse of 27 months there was no limb-length inequality
      exceeding 1 cm and no malunion. We feel that femoral fractures in patients aged 5
      10 years can be safely treated with retrograde flexible intramedullary nailing
      with minimal risk of surgical complications.

PMID- 11954852
TI  - Conservative treatment of subtalar dislocations.
AB  - Forty-five patients who presented between 1983 and 1998 with acute closed
      dislocation of the subtalar joint were selected for this study. There were 37
      medial and eight lateral dislocations. The mean follow-up was 7.5 years (range: 2
      17 years). The mean American Orthopaedic Foot and Ankle Society Hindfoot Score
      (AOFAS) at follow-up was 84. Subtalar fusion was required in one patient with
      persistent severe hind-foot instability. There was no significant difference in
      the AOFAS score between medial and lateral subtalar dislocations. We conclude
      that pure subtalar dislocation produced by low energy trauma, promptly reduced
      and immobilised for 4 weeks has a favourable long-term outcome.

PMID- 11954853
TI  - Octreotide scanning in the detection of a mesenchymal tumour in the pubic
      symphysis causing hypophosphataemic osteomalacia.
AB  - Oncogenic hypophosphataemic osteomalacia is a rare condition. The causative
      tumour is often difficult to locate. Primary tumours have been reported in the
      head and neck, skeleton, and soft tissue. Octreotide scanning was used in this
      case and detected a mesenchymal tumour in the pubic symphysis.

PMID- 11954854
TI  - Modified Boytchev procedure for the treatment of recurrent anterior dislocation
      of the shoulder.
AB  - From January 1990 to December 1998, 48 patients with 50 recurrent anterior
      dislocations of the shoulder were treated using a modified Boytchev procedure.
      The age of the patients varied from 18 to 35 years (average 24.7 years). The
      follow-up period was in average 88 (26-132) months. Six patients were lost in
      follow-up. Forty-two shoulders showed excellent results. There was one traction
      injury of the musculocutaneous nerve and one patient with immediate recurrence of
      the dislocation. Superficial wound infection occurred in five cases, all of which
      were controlled by antibiotics.

PMID- 11954855
TI  - Mechanisms and current treatments of urogenital dysfunction in multiple
      sclerosis.
AB  - The majority of patients with multiple sclerosis (MS) suffer from lower urinary
      tract symptoms and sexual dysfunction at some stage of the disease. This has a
      negative impact on the quality of life of patients as well as causing concern to
      caregivers and family. Neurologists can now treat most of these symptoms by a
      number of pharmacological and nonpharmacological methods. This review presents
      the neuroanatomy, neurophysiology, neuropharmacology and pathophysiology of the
      urinary bladder and sexual organs, and the biological mechanisms underlying
      urogenital dysfunction in MS patients. Current treatment options for urinary and
      sexual dysfunction are reviewed. As most urogenital symptoms of MS can now be
      treated by conservative means, expert urological or gynaecological consultation
      should be requested only if more aggressive diagnostic or therapeutic measures
      are needed.

PMID- 11954856
TI  - Effectiveness of intravenous immunoglobulin treatment in adult patients with
      steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis.
AB  - Randomized Controlled Trials have not let established the best pharmacological
      management of Acute Disseminated Encephalomyelitis (ADEM). High dose steroids are
      usually employed with good results, but in a few cases the clinical outcome is
      poor. In other patients, particularly those affected by the site restricted ADEM
      variants (myelitis), the disease shows a recurrent course resembling that of
      Multiple Sclerosis. We present here five patients, 3 of them affected by classic
      disseminated encephalomyelitis and 2 by a post infectious myelitis, which showed
      a good response to intravenous immunoglobulin (IVIg) after steroid treatment
      failure. In our report high dose steroids administration was substantially
      uneffective in all but one case, who showed a good response only during the first
      episode. On the contrary IVIg injection (0,4 gr/kg/day) produced a marked
      functional improvement in all patients starting within the first five days of
      drug administration and reaching a maximum within three weeks. One patient
      experienced a good effect nothwithstanding a steady dysability. In all cases,
      clinical evidence was supported by MRI controls showing improving posttreatment
      changes.

PMID- 11954857
TI  - Pure alexia in a Japanese-English bilingual: dissociation between the two
      languages.

PMID- 11954858
TI  - Effect of sympathetic blockade on cerebral perfusion demonstrated on Tc-99m HMPAO
      SPECT.

PMID- 11954859
TI  - Lack of association between NOS3 poly morphism and Italian sporadic and familial
      Alzheimer's disease.

PMID- 11954860
TI  - Penile erections and hypersexuality induced by pergolide treatment in advanced,
      fluctuating Parkinson's disease.

PMID- 11954861
TI  - Constantin von Monakow (1853-1930).

PMID- 11954862
TI  - Perverted head-shaking nystagmus: two possible mechanisms.

PMID- 11954864
TI  - Disability and lesion load in MS: a reassessment with MS functional composite
      score and 3D fast FLAIR.
AB  - The correlation between T2 lesion load (LL) detected on conventional MR sequences
      and disability assessed by the Expanded Disability Status Scale (EDSS) in
      multiple sclerosis (MS) is, at best, moderate. The present study was performed to
      determine whether the correlation between disability and LL is improved by (i)
      use of the more sensitive three-dimensional fast fluid-attenuated inversion
      recovery (3D-fast FLAIR) sequence; (ii) application of the newly devised MS
      functional composite (MSFC) score. Forty-one patients with clinically definite or
      probable MS were studied. All had been followed prospectively for 14 years since
      their first symptom. EDSS and MSFC score were assessed. Imaging was performed
      with 3D-fFLAIR, fast spin-echo (FSE), and T1 weighted SE sequences. 3D-fFLAIR
      detected a 34% higher LL than FSE, but did not improve the correlation between T2
      LL and EDSS (r = 0.51 and r = 0.53); the correlation was stronger with T1 LL (r =
      0.57). The MSFC score did not significantly correlate with T2 LL or T1 LL. The
      robust correlation in this cohort between T2 LL and EDSS may reflect the
      homogeneous disease duration and the wide spread of disability. This correlation
      was not improved by the increased detection of T2 lesions with the 3D-fFLAIR
      sequence. The stronger correlation between T1 LL with EDSS is consistent with the
      finding that this subgroup of lesions represent areas of more severe tissue
      damage. The MSFC score did not improve the clinico-radiological paradox that is
      found in MS, despite including information on cognitive function.

PMID- 11954865
TI  - Distinct pattern of age-specific incidence of Guillain-Barre syndrome in Harbin,
      China.
AB  - We describe the age-and sex-specific incidence of Guillain-Barre syndrome (GBS)
      in Harbin, China, based on the information from a prospective survey among a well
      defined large population during one year. A network of physicians reported
      incident patients with a GBS diagnosis from a general population of 5.4 million
      inhabitants in Harbin, China, during the period from 1 October 1997 to 30
      September 1998. Each reported patient was examined by senior neurologists and the
      GBS diagnosis was validated according to standard diagnostic criteria. All GBS
      patients were followed-up for six months after onset. Admission registers at all
      hospitals in Harbin were also checked afterwards for screening patients with a
      GBS diagnosis who might have been missed. During the study period, 79 patients
      with a GBS diagnosis were reported. After validation, the GBS diagnosis was
      confirmed in 70 patients. Another GBS patient was found through the screening of
      admission registers at hospitals. Among them, 36 GBS patients were residents in
      Harbin and the other 35 patients were from geographical areas out of Harbin. The
      GBS incidence, age-adjusted to the European standard population, was 0.66 (95% CI
      0.46-0.91) per 100,000 person-years, with a male to female ratio of 1.4. The
      highest GBS incidence was found in the youngest age-group and the incidence among
      the elderly was remarkably lower than those reported from other populations in
      Western countries. Possible explanations for the distinct pattern of age-specific
      incidence of GBS are discussed. Further studies are needed.

PMID- 11954866
TI  - MRI characteristics of acute and subacute brainstem and thalamic infarctions:
      value of T2- and diffusion-weighted sequences.
AB  - MRI including diffusion-weighted sequences (DW-MRI) has demonstrated its high
      sensitivity for acute supratentorial ischemic lesions. In this study we examined
      the sensitivity of different MRI sequences for the detection of acute brainstem
      and isolated thalamic infarctions. Diffusion- and T2-weighted MRI of 45
      consecutive patients with signs and symptoms of infratentorial and thalamic
      infarction between 6/1997 and 1/2000 were analysed. The time between the onset of
      symptoms and the first MRI varied between 2 hours to 7 days with a median of 2
      days. MRI repeats were performed in 4 patients in whom the clinical brainstem
      infarction had not been detected initially. Lesion detectability and size were
      evaluated for different brainstem and thalamic localizations. An acute brainstem
      or thalamic infarction as defined by the clinical condition could be identified
      in all patients by comparison of DW-MRI and T2-weighted images. Pons in farctions
      were the largest, followed by midbrain and thalamic lesions. Medulla oblongata
      infarctions were small in comparison. Pons, mid-brain and thalamic infarctions
      were reliably identified beginning 12 hours after the onset of symptoms. In
      contrast, detectability of medulla oblongata infarctions varied within the first
      24 hours and their overall visibility was worse than that of other brainstem
      infarctions corresponding to their small size. However, regardless of loca tion,
      none of the 3 infarctions examined within the first 5 hours after the onset of
      symptoms could be identified. These lesions were demonstrated in follow-up
      examinations. In conclusion, pontine, midbrain and thalamic infarctions can
      reliably be visualized by a combination of DW-MRI and T2-weighted images
      beginning 12 hours after the ischemic attack. However, sensitivity seems to be
      lower earlier than 12 hours after ischemia and for medulla oblongata lesions.

PMID- 11954867
TI  - Multi-slice CT angiography in the evaluation of patients with acute
      cerebrovascular disease--a promising new diagnostic tool.
AB  - Single-slice computed tomographic angiography (CTA) is an established imaging
      method for the cerebrovascular system (CVS), but it suffers from technical
      limitations with respect to the coherent high resolution visualization of longer
      vascular segments, such as the extra- and intracranial CVS. The recently
      introduced multi-slice (MS) technology has been attributed with a superior
      imaging quality for angiographic procedures due to increased scan speed and
      improved spatial resolution. The purpose of this study was to evaluate the
      suitability of multi-slice CTA (MS-CTA) for the assessment of the arteriovenous
      CVS in patients with acute symptoms of either arterial or venous occlusive
      diseases. 41 patients with clinically suspected acute cerebral ischaemia
      (hemispheric in 29 and vertebrobasilar in 12 patients) and 4 patients with
      suspected cerebral venous thrombosis (CVT) underwent CTA in a MS-CT scanner. In
      addition, doppler ultrasonography (DUS) was erformed in 34, magnetic resonance
      angiography (MRA) in 5 and digital subtraction angiography (DSA) in 6 patients.
      All findings were reviewed for stenoses or occlusion of the extra-and
      intracranial CVS and correlated with the clinical outcome. In 43 (96%) of 45
      patients, MS-CTA yielded images of diagnostic quality with comprehensive
      visualization of the arterial and venous CVS including the cervical carotid
      bifurcation, the third segment of the major cerebral arteries and the dural sinus
      as well as internal cerebral veins. In 2 patients, assessment of the carotid
      bifurcation was limited because of tooth artefacts. In all patients, in whom
      imaging and clinical follow-up proved a non-lacunar infarction (n = 22), MS-CTA
      detected the underlying vascular pathology. Suspected CVT could be confirmed in 2
      and ruled out in another 2 patients through MS-CTA. In conclusion, multi-slice CT
      an giography may be a promising new diagnostic tool for the rapid and
      comprehensive assessment of the arteriovenous CVS in patients with clinical signs
      of acute cerebrovascular diseases.

PMID- 11954868
TI  - Monthly corticosteroids decrease neutralizing antibodies to IFNbeta1 b: a
      randomized trial in multiple sclerosis.
AB  - Neutralizing antibodies (NAB) to interferon beta (IFNbeta) occur in some multiple
      sclerosis (MS) patients, particularly during the first year of treatment. The
      presence of NAB may be associated with an attenuation of the therapeutic effect.
      The aim of this study was to compare the frequency of NAB occurrence in patients
      treated with IFNbeta-1 b with that in patients treated with IFNbeta-1 b combined
      with monthly pulses of intravenous methylprednisolone (MP). One hundred and sixty
      one patients with relapsing-remitting MS were randomized in two treatment arms: 8
      MIU of IFNbeta- 1 b subcutaneously injected every other day either alone or in
      combination with 1000 mg of monthly intravenous MP. NAB were evaluated at
      baseline and at months 3,6,9,12 and 15 by the MxA assay in a specialized
      laboratory. Positivity was defined as a titer of > or = 20 neutralizing units
      according to two different definitions: I) one or more non-consecutive positive
      samples, II) at least two consecutive positive samples. NAB (definition I) were
      observed in 26.8% of patients in the IFNbeta-1 b alone arm and in 12.1% of
      patients in the combination therapy arm (p = 0.05 by the chi-square test), which
      corresponds to a relative reduction of 54.9%, whereas according to definition II,
      these figures dropped to 22.5 % for the IFNbeta-1 b alone arm, and 10.6% for the
      combination therapy arm (relative reduction 52.9%, p = 0.10, NS). A higher
      probability of remaining in the NAB-free status was observed in patients treated
      with the combination therapy (p = 0.031 for definition I and p = 0.o49 for
      definition II, by the Wilcoxon-Gehan test). Methylprednisilone combined with
      IFNbeta-1 b reduces the incidence of neutralizing bodies to in terferon-beta
      during the first year of treatment in MS patients.

PMID- 11954869
TI  - A randomized, double-masked, crossover comparison of the efficacy and safety of
      botulinum toxin type A produced from the original bulk toxin source and current
      bulk toxin source for the treatment of cervical dystonia.
AB  - In 1997, the US FDA approved a new bulk toxin source (now referred to as current)
      for the manufacture of botulinum toxin type A (BTX-A). The current BTX-A
      preparation has a lower neurotoxin complex protein load than the original BTX-A
      preparation, which may reduce antigenic potential. The present double-masked,
      multicenter study compared the efficacy and safety of BTX-A (BOTOX) produced from
      both original and current bulk toxin sources for the treatment of cervical
      dystonia. Patients (N = 133) were injected with BTX-A produced from original and
      current bulk toxin sources using a crossover design. Adverse events were assessed
      at each visit. Efficacy was assessed at 2 and 6 weeks post-injection using the
      severity and pain-disability subscales of the Toronto Western Spasmodic
      Torticollis Rating Scale (TWSTRS). Mean BTX-A doses were comparable (original:
      155 U, current: 156 U). Both BTX-A preparations produced similar, statistically
      significant reductions in TWSTRS severity and pain-disability scores at weeks 2
      and 6 post-injection. The original and current BTX-A preparations showed no
      significant differences in adverse events, including both treatment-related (34%,
      31%) and treatment-unrelated (27%, 32%), respectively. BTX-A produced from the
      original and current bulk toxin sources showed comparable efficacy and safety in
      the treatment of cervical dystonia; both significantly reduced dystonia severity
      and pain.

PMID- 11954870
TI  - Comparison of preseptal and pretarsal injections of botulinum toxin in the
      treatment of blepharospasm and hemifacial spasm.
AB  - Although the beneficial effect of subcutaneous injections of botulinum toxin type
      A (BTX-A) is well known in both blepharospasm and hemifacial spasm, the position
      of the injection sites around the orbicularis oculi may influence the
      effectiveness and side effects. Here we report results of preseptal and pretarsal
      BTX-A injections in 53 patients (25 blepharospasm and 28 hemifacial spasm) in
      whom we used both injection techniques successively. Pretarsal injections were
      used in 102 out of 186 treatments in blepharospasm group and in 84 out of 202
      treatments in hemifacial spasm group. Pretarsal BTX-A treatment produced
      significantly higher response rate and longer duration of maximum response in
      both patient groups. This technique was also associated with a lower frequency of
      major side effects such asptosis. We concluded that injections of BTX-A into the
      pretarsal, rather than the preseptal portion of the orbicularis oculiis more
      effective for treatment of involuntary eyelid closure due to contractions of this
      muscle.

PMID- 11954871
TI  - Clinical and serological characteristics of 125 Dutch myositis patients. Myositis
      specific autoantibodies aid in the differential diagnosis of the idiopathic
      inflammatory myopathies.
AB  - The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of
      systemic diseases that include the familiar disease entities of dermatomyositis
      (DM), polymyositis (PM), and inclusion body myositis (IBM). A subset of patients
      has unique autoantibodies which are specific for IIM (myositis specific
      autoantibodies; MSAs). We studied the clinical and serological characteristics of
      IIM in 125 Dutch patients. Sera were analysed by immunoblotting, enzyme-linked
      immunosorbent assay, and immunoprecipitation. The most frequently encountered MSA
      was the anti-Jo-1 autoantibody (20%), followed by anti-tRNAHis (6%), anti-Mi-2
      (6%), and anti-SRP (4%). The presence of certain MSAs was clearly associated with
      specific clinical characteristics. Anti-Jo-1 and anti-tRNAHis were associated
      with the anti-synthetase syndrome, anti-SRP with PM with severe myalgia and
      arthralgia and a moderate response to immunosuppressive treatment. A novel
      finding was the presence of anti-Mi-2, not only in DM, but also in PM. MSAs were
      frequently present in DM/PM sera, but were hardly ever detected in the sera of
      IBM patients. The few IBM patients with MSAs demonstrated a significant response
      to immunosuppressive treatment. It can be concluded that MSAs define specific
      clinical syndromes within the spectrum of IIM and that they can assist in the
      differential diagnosis and treatment plan of these enigmatic disorders by
      virtually excluding IBM by their presence, and by potentially identifying a
      subgroup of steroid-responsive IBM patients.

PMID- 11954872
TI  - Efficacy of botulinum toxin A in upper limb function of hemiplegic patients.
AB  - Botulinum toxin A has been reported to reduce spasticity and increase the comfort
      of hemiplegic patients. The aim of this study was to assess the efficacy of the
      treatment on disability, especially in manual activities, and to attempt to
      identify predictive factors of improvement. Twenty patients (mean age: 54.4
      years; M: 14; right hemiplegia: 12) were included, with a delay of at least three
      months after unilateral hemispheric stroke. Botulinum toxin A (BOTOX) was
      injected into the arm adductors (8 cases), forearm flexors (17 cases), pronators,
      wrist and finger flexors (20 cases),with a total dose of 200 to 300 U.
      Examination (day 1 and 15, month 2 and 5) consisted of spasticity assessment
      (modified Ashworth scale), muscle strength, passive range of motion (goniometry),
      and pain, followed by functional tests, especially the Rivermead Motor Assessment
      (RMA) and Nine-hole Peg Test (NHPT). Performance in daily living was assessed
      with the Functional Independence Measure (FIM), and an original analysis of hand
      grasp, grip and pinches used in domestic activities (9 items), and of comfort of
      patients and caregivers. Significant reduction in spasticity was observed on the
      elbow flexors, pronators, wrist and fingers flexors, especially at day 15 (mean
      0.90 to 1 point), with wide variations in effect. Muscle strength was increased
      in wrist and fingers extensors, with concomitant increase in the opening of the
      thumb to index finger space. There was no effect on the NHPT requiring distal
      manipulation, but the RMA, which especially concerned picking up and releasing a
      tennis ball, showed significant improvement. Furthermore, use of the upper limb
      in daily living increased, particularly for internal grasping of objects, and for
      grasping by the top, transporting and releasing of objects. Patients and
      caregivers re ported facilitation in dressing, and in proximal and distal care of
      the upper limb. The global flexor position of the limb improved. Ad verse
      reactions were rare and mostly consisted of transitory pain during injection. The
      improvement in the RMA was better explained by the quality of the initial motor
      command on distal prehension (positive correlation with motor strength), and that
      in hand using in domestic activities by a lower level of spasticity on pronators
      and wrist flexors (negative correlations with spasticity). Conversely, the
      severity of the motor deficit (negative correlations with motor strength) and a
      high level of spasticity before injection (positive correlations with spasticity)
      mostly explained the improvement in comfort. In conclusion, botulinum toxin A is
      efficient in improving hand use in patients with relatively preserved distal
      motricity, and in increasing comfort in patients with severe global disorders.

PMID- 11954873
TI  - Spectrum of medial medullary infarction: clinical and magnetic resonance imaging
      findings.
AB  - Among 4200 consecutive patients admitted to three hospitals with acute ischemic
      stroke, we found only 11 patients in whom magnetic resonance imaging (MRI) had
      proved that they had medial medullary infarction (MMI). In our centers, patients
      with MMI were less than 1% of those with vertebrobasilar stroke. The infarcts
      documented by MRI were unilateral in 10 patients and bilateral in one. On clinico
      topographical analysis there were four clinical patterns: (1) Classical
      Dejerine's syndrome was the most frequent, consisting of contralateral
      hemiparesis, lemniscal sensory loss and ipsilateral lingual palsy in 7 of the
      eleven patients. (2) Pure hemiparesis was present in 2 patients; (3) Sensorimotor
      stroke was present in 1 patient with contralateral hemiparesis, hypesthesia and
      mild decrease in pain sensation without lingual palsy; (4) Bilateral MMI syndrome
      in 1 patient, accompanied by tetraparesis, bilateral loss of deep sensation,
      dysphagia, dysphonia and anarthria. Presumed causes of MMI were intrinsic branch
      penetrator artery disease with concomitant vertebral artery stenosis in 6 of the
      11 patients, vertebral artery occlusion in 2, dolichoectatic vertebrobasilar
      arteries in 2, a source of cardiac embolism in 1. Prognosis at 3 months was
      favorable in 8 patients, but the patient with bilateral MMI syndrome had
      persisting motor deficit causing limitation of daily activities, and 2 died from
      systemic causes. The classical triad of acute MMI facilitates the diagnosis,
      although the recognition of this syndrome in patients with incomplete
      manifestations can be difficult and occurs more frequently than commonly thought.
      Moreover, vertebral artery atherosclerosis and branch atheromatous disease of the
      penetrating arteries are the main causes of medullary infarction.

PMID- 11954874
TI  - Chemotherapy-induced peripheral neuropathy.
AB  - The induction of peripheral neuropathy is a common factor in limiting therapy
      with chemotherapeutic drugs. Little is known about the mechanisms responsible for
      the development of neuropathy. Depending on the substance used, a pure sensory
      and painful neuropathy (with cisplatin, oxaliplatin, carboplatin) or a mixed
      sensorimotor neuropathy with or without involvement of the autonomic nervous
      system (with vincristine, taxol, suramin) can ensue. Neurotoxicity depends on the
      total cumulative dose and the type of drug used. In individual cases neuropathy
      can evolve even after a single drug application. A general predisposition for
      developing a chemotherapy-induced neuropathy has been observed in nerves
      previously damaged by diabetes mellitus, alcohol or inherited neuropathy. The
      recovery from symptoms is often incomplete and a long period of regeneration is
      required to restore function. Up to now, no drug is available to reliably prevent
      or cure chemotherapy-induced neuropathy.

PMID- 11954875
TI  - Treatment of acute cluster headache with 20 mg sumatriptan nasal spray--an open
      pilot study.
AB  - We investigated the efficacy and tolerability of 20 mg sumatriptan nasal spray in
      the acute treatment of cluster headache attacks in an open-label study. 10
      patients met the criteria of the International Headache Society (IHS) for
      episodic or chronic cluster headache and were enrolled in our study. The primary
      efficacy measure was "pain free" 30 minutes after treatment. Secondary end-points
      included "headache response" (defined as headache improvement from "very severe",
      "severe" or moderate" pain to "mild" or "no" pain) 15, 30, 45 and 60 minutes
      after treatment. We also assessed the participant's overall treatment
      satisfaction at the end of the study. Sumatriptan nasal spray was applied in 154
      "moderate" to "very severe" cluster headache attacks. 30 minutes after nasal
      spray application, 50% of attacks were completely aborted and 58% of attacks
      responded to treatment. The overall efficacy of sumatriptan nasal spray was
      considered "excellent" in two, "good" in four, "reasonable" in two and "poor" in
      two patients. Eight patients indicated their intention to treat further attacks
      with intranasal sumatriptan. Seven patients were interviewed after a follow-up
      period of six months. Four patients continued to treat all cluster headache
      attacks with the intranasal sumatriptan formula, two patients had switched to
      subcutaneous sumatriptan and one patient was in remission since the end of the
      study. We conclude that 20 mg sumatriptan nasal spray might be an alternative
      therapy for the treatment of cluster headache attacks, but double-blind studies
      are needed to further evaluate its efficacy.

PMID- 11954876
TI  - Clinically asymptomatic axial disease in psoriatic spondyloarthropathy. A
      retrospective study.
AB  - The aim of this study was to analyse retrospectively the prevalence and the
      clinical features of clinically asymptomatic axial involvement in patients with
      psoriasis and axial radiological features of spondyloarthropathy (PsSpA). We
      performed a cross-sectional study based on the clinical records of 70 patients,
      44 men and 26 women, with a mean age of 48.7+/-14.2 years. PsSpA was defined by
      the presence of radiographic sacroiliitis (SI) greater than or equal to grade 2,
      and/or any other typical radiological sign of spondylitis in patients with
      psoriasis. When the radiological signs were present in the absence of
      inflammatory back pain and/or buttock pain, patients were grouped as having
      asymptomatic axial disease. HLA-B27 was determined by serological methods in the
      70 patients and in 82 healthy controls from our general population. Fourteen
      patients (20%), 11 with radiological SI, two with facet joint erosion-fusion and
      one with aseptic discitis, showed no evidence of symptomatic spinal disease.
      Twenty-nine patients (41%) showed cervical spine disease (CSD), but only 17 of
      them (58.6%) had pain and rigidity at this level, whereas 12 (41.4%) did not show
      clinical symptoms. CSD was associated with duration of arthritis (P = 0.043) and
      peripheral erosions (P = 0.037). HLA-B27 correlated well with bilateral SI (P =
      0.002) and PsSpA (P<0.0004, RR 6.4), but showed no association with unilateral SI
      nor with syndesmophytes or asymptomatic disease. Univariate analysis demonstrated
      associations between symptomatic disease and longer duration of arthritis (P =
      0.041) and higher IgM values (P = 0.05). There is a high prevalence of
      asymptomatic involvement in patients with PsSpA The significance of these
      asymptomatic changes is not known, but they probably represent a common
      characteristic of spondyloarthropathies rather than a specific feature associated
      with psoriasis.

PMID- 11954877
TI  - Glomerulonephritis in Behcet's disease: report of seven cases and review of the
      literature.
AB  - Despite being recognised much more frequently than in the past, renal involvement
      has not previously been regarded as a feature of Behcet's disease (BD). In this
      study we aimed to assess the frequency of renal involvement in BD by performing
      urinalyses of 674 consecutive BD patients; we also retrospectively evaluated the
      charts of 4212 BD patients for the incidence of glomerulonephritis (GN). Urinary
      abnormalities (proteinuria and/or haematuria) were present in 10.8%; and during a
      period of 23 years GN was detected by renal biopsy in seven (0.16%) BD patients.
      Two patients with GN were lost to follow-up; end-stage renal failure developed in
      only one patient, and she underwent renal transplantation. We were unable to
      determine any pathognomonic feature that was predictive of renal involvement.
      Although males tend to have a more serious clinical course of BD the incidences
      of urinary abnormalities and GN were similar in both sexes in our series.
      According to our results, we can conclude that urinary abnormalities are more
      frequent in BD; however, serious renal lesions develop in only very few of these
      patients.

PMID- 11954878
TI  - Relationship between chest expansion and respiratory muscle strength in patients
      with primary fibromyalgia.
AB  - In this paper the assessment of the relationship between chest expansion with
      maximal inspiratory (MIP) and expiratory pressures (MEP) in primary fibromyalgia
      (FM) syndrome is discussed. Chest expansion (CE) measurements, spirometric
      values, and MIP and MEP values in 30 female patients with primary FM are compared
      with 29 healthy age-matched female controls. Patients with FM had lower CE, MEP
      and MIP values than controls. CE correlated significantly with MIP and MEP
      values. There was no significant difference between groups in spirometric values.
      Our results indicate that patients with FM have impaired respiratory muscle
      strength, and measurement of CE may be a useful clinical parameter. Despite its
      limitations CE may reflect respiratory muscle strength. It is worth following up
      these data in a wider and controlled series, with ancillary tests in addition to
      the MIP and MEP.

PMID- 11954879
TI  - Interleukin-2 levels are elevated in the bone marrow serum of patients with
      mutilans-type rheumatoid arthritis.
AB  - In order to investigate the pathogenesis of mutilans-type rheumatoid arthritis
      (RA), we measured cytokine levels in the bone marrow serum of patients with RA.
      We studied 35 patients with non-mutilans RA, 19 with mutilans RA, and 20 patients
      with osteoarthritis (OA) undergoing joint surgery. At the time of surgery, iliac
      bone marrow and peripheral blood were sampled from all 74 patients and cytokine
      levels measured. The serum levels of five cytokines (IL-1beta, IL-2, IL-3, IL-6
      and GM-CSF) were measured by ELISA. Haematologic and inflammatory factors were
      also measured. Levels of IL-2, IL-6 and GM-CSF in bone marrow serum were
      significantly higher in all RA patients than in those with OA. Mean (+/-SD) IL-2
      levels were significantly higher in patients with mutilans-type RA (309.8+/-686.3
      pg/ml) than in patients with other types of RA (66.5+/-173.1 pg/ml; P<0.01). IL-2
      was detected significantly more often in patients with mutilans-type RA than in
      patients with other types of RA (P < 0.01). Inflammatory factors were higher in
      all RA groups than in OA patients. However, the haematologic and immunologic
      variables were no different between mutilans RA and other types of RA. No
      correlations were observed between IL-1beta, IL-2, IL-3, IL-6 and GM-CSF levels
      and these laboratory variables. In patients with mutilans-type RA, IL-2 levels in
      the bone marrow serum were significantly higher than in patients with other types
      of RA or with OA. This elevation does not appear to be related to systemic
      inflammation, as there was no correlation with other inflammatory factors.

PMID- 11954880
TI  - Comparative tolerability of paracetamol, aspirin and ibuprofen for short-term
      analgesia in patients with musculoskeletal conditions: results in 4291 patients.
AB  - The aim of this blinded, randomised, multicentre study was to compare the
      tolerability of aspirin, paracetamol and ibuprofen in common pain resulting from
      musculoskeletal conditions (MSC) in general practice with patients with other non
      MSC pain conditions. Patients took aspirin, paracetamol (both up to 3g daily) or
      ibuprofen (up to 1.2g daily) for up to 7 days. The main outcome was the rate of
      significant adverse events (SGAE). Four thousand two hundred and ninety one
      patients with MSC were evaluable (1436 aspirin, 1423 paracetamol, 1432 ibuprofen)
      and 4101 (95.5%) were per-protocol. A group of 4342 patients included for other
      (non-MSC) mild to moderate pain conditions was used for comparison. In the MSC
      group, SGAE were reported by 20.5% of patients with aspirin, 17.0% with
      paracetamol and 15.0% with ibuprofen. Ibuprofen was statistically equivalent to
      paracetamol and better tolerated than aspirin (p <0.0001). Ibuprofen was
      associated with fewer digestive system AE (4.4%) than aspirin (8.6%, p<0.0001)
      and paracetamol (6.5%, p <0.02). The non-MSC group showed similar intertreatment
      differences, but experienced fewer SGAE. No serious digestive events were
      observed with any of the three treatments in either group. These results show
      that in patients with mild to moderate pain resulting from MSC, ibuprofen given
      in OTC doses for 6 days is as well tolerated as paracetamol and better tolerated
      than aspirin.

PMID- 11954881
TI  - Global functional status in rheumatoid arthritis: disease duration and patient
      age.
AB  - With the aim of clarifying whether patient age could be an additional explanation
      for the differences in the clinical expression of rheumatoid arthritis (RA) found
      in different populations, we evaluated the possibility of patient age being a
      significant factor associated with global functional status, independent from
      disease duration. Our present results suggest that both disease duration and
      patient age are major factors in the global functional status of patients with
      RA, and that patient age is particularly important when a subgroup of patients
      with more than 60 years of age and more than 20 years of disease duration is
      considered. These data are relevant when comparing two different RA groups: not
      only should we have a similar mean age and mean disease duration, but also the
      subgroups of patients more than 60 years of age and with more than 20 years of
      disease duration should correspond to equivalent proportions in the populations
      studied.

PMID- 11954882
TI  - Self-reported symptoms among Danish women following cosmetic breast implant
      surgery.
AB  - The aim of this study was to examine self-reported symptomatology and to identify
      distinctive characteristics among women with silicone breast implants (SBI).
      Using the Danish hospital and population registers we identified three groups of
      women with a hospital diagnosis of muscular rheumatism (a nonspecific soft-tissue
      diagnostic code) who had previously undergone SBI surgery (n = 28), breast
      reduction surgery (n = 29) or no breast surgery (n = 27); and three groups of
      women without a diagnosis of muscular rheumatism who had undergone SBI surgery (n
      = 21), breast reduction surgery (n = 27) or no breast surgery (n = 56). All study
      subjects completed a self-administered questionnaire focusing on sociodemographic
      factors, lifestyle habits, somatic symptoms and psychological symptoms. Women
      with SBI and women with breast reduction with no previous diagnosis of muscular
      rheumatism had similar patterns of reporting for most symptoms and
      characteristics. They reported significantly more somatic symptoms and
      psychological distress, including somatisation, obsessive-compulsiveness and
      depression, than women with no breast surgery. No significant differences in self
      reported symptomatology and characteristics were observed among the three groups
      of women with a previous diagnosis of muscular rheumatism. Overall, women with
      prior muscular rheumatism reported more symptoms than those without. We concluded
      that self-reported somatic symptoms among women with SBI were similar to those of
      controls. Women with cosmetic breast surgery appear to have distinctive
      psychological characteristics. Our study emphasises the importance of taking the
      psychological profile and previous history of rheumatic diseases into account
      when examining women with SBI.

PMID- 11954883
TI  - Effects of needle-arthroscopic lavage with different volumes of fluid on knee
      synovitis in rheumatoid arthritis.
AB  - To determine the appropriate volume of physiological fluid needed to effectively
      reduce synovitis and to determine the indications for intra-articular lavage of
      knee joints with rheumatoid arthritis (RA), intraarticular lavage with different
      volumes of physiological fluid via needle arthroscopy were performed on 102
      rheumatoid knees in 98 patients (25 males, 77 females) with an average age of 46
      years at the time of operation. Intra-articular lavage of a knee joint with 5 or
      10 l of physiological fluid gave better clinical results than did intra-articular
      lavage with 0.5-1.5 l. There was no difference between the beneficial effects of
      intraarticular lavage using 5 1 or 10 l of fluid. The preoperative conditions
      (CRP, frequency of the susceptible factors of HLA-DRB1 alleles, radiological
      change in the knee joint) and the intraoperative chondroscopic assessments were
      correlated with clinical improvement. Our study demonstrated that intra-articular
      lavage with 5 l of physiological fluid performed using needle arthroscopy was
      beneficial. The following points at least should be checked before performing
      intra-articular lavage: (1) CRP is not elevated to a high level (> or =5 mg/dl),
      (2) the patient does not have susceptible factors in both HLA-DRB1 alleles, (3)
      the grade of rheumatoid knee is below Larsen II in preoperative X-ray findings,
      and (4) the degree of cartilage damage is not more than grade 3 in arthroscopic
      findings.

PMID- 11954884
TI  - Effects of cisapride on oesophageal transit of solids in patients with
      progressive systemic sclerosis.
AB  - In most patients with progressive systemic sclerosis (PSS) the oesophagus is
      affected. Reflux symptoms are most frequent, whilst dysphagia also occurs.
      Cisapride, a prokinetic agent, may enhance motility along the gastrointestinal
      tract. The effects of cisapride on oesophageal transit were evaluated in 12 PSS
      patient using a solid-phase radionuclide oesophageal transit study. Each PSS
      patient was given cisapride 10 mg or placebo orally three times a day in a
      random, double-blind, crossover fashion. The results show that cisapride does not
      seem to have any impact on oesophageal transit in patients with PSS.

PMID- 11954885
TI  - Immunohistological indication for arthroscopic synovectomy in rheumatoid knees:
      analysis of synovial samples obtained by needle arthroscopy.
AB  - To determine the histological indication for arthroscopic synovectomy in
      rheumatoid knees, 23 patients underwent lavage and biopsy by needle arthroscopy.
      Eighty-one patients were treated with arthroscopic knee synovectomy after needle
      arthroscopy, and 51 of these patients underwent only arthroscopic synovectomy.
      Thirty patients who showed no improvement following arthroscopic synovectomy
      underwent open surgical synovectomy. Intra-articular lavage of knee joints by
      needle arthroscopy did not result in any clinical improvements. In the patients
      who underwent only arthroscopic synovectomy, two groups (only macrophages, no
      macrophages or B cells) showed clinical improvement (symptoms of the knee, ESR,
      RF). Patients in whom open surgical synovectomy was performed because of the
      failure of arthroscopic synovectomy showed clinical improvement. However, there
      was a significant loss of movement in the knee joint and more severe radiological
      deterioration in patients who underwent open surgical synovectomy than in those
      who underwent only arthroscopic synovectomy. Arthroscopic synovectomy should be
      used for rheumatoid patients with synovial tissue containing only macrophages or
      none of these two cells.

PMID- 11954886
TI  - Association between serum inflammatory cytokines and disease activity in juvenile
      idiopathic arthritis.
AB  - Circulating interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF
      alpha), osteocalcin, and conventional parameters of inflammation were examined
      serially in 14 children with juvenile idiopathic arthritis (JIA) to determine any
      correlation with the disease activity. Serum IL-1beta was undetectable in all JIA
      patients. Serum IL-6, white blood cell counts, platelet counts, erythrocyte
      sedimentation rate and C-reactive protein levels were significantly elevated in
      the active phase of JIA, whereas hemoglobin levels were significantly lower.
      Osteocalcin levels were decreased and TNF-alpha increased in active JIA status,
      but these differences showed no statistical significance. We concluded that
      inflammatory cytokines play an important role in JIA. Monitoring IL-6 in children
      with JIA is useful in determining disease activity and response to therapy. These
      findings confirm earlier reports.

PMID- 11954887
TI  - Thrombotic thrombocytopenic purpura as an initial presentation of primary
      Sjogren's syndrome.
AB  - A healthy woman presented with ecchymoses due to thrombocytopenia, with numerous
      bone marrow megakaryocytes, microangiopathic haemolytic anaemia, disorientation,
      irritability, and normal renal function. Thrombotic thrombocytopenic purpura
      (TTP) was diagnosed and treated successfully by plasma exchange therapy, both on
      presentation and during a further three relapses. The TTP was considered
      idiopathic until, 4 months later, definite primary Sjogren's syndrome (1 degree
      SS) was diagnosed following the appearance of sicca symptoms. Only four similar
      cases have been cited in the literature. TTP should be added to the varied
      haematological manifestations that may occur in patients with 1 degree SS. The
      possible presentation of 1 degree SS not with classic sicca symptoms but rather
      with haematological abnormalities, including TTP, should be recognised.

PMID- 11954888
TI  - Pseudothrombophlebitis in a patient with Behcet's syndrome: Doppler ultrasound
      and magnetic resonance imaging findings.
AB  - A 33-year-old man with a known diagnosis of Behcet's syndrome (BS), presented
      with pseudothrombophlebitis resulting from acute rupture of a popliteal cyst.
      Doppler ultrasound and magnetic resonance imaging findings are explained.
      Differentiation of rupture of a Baker's cyst from true thrombophlebitis,
      especially in patients with BS, who are potentially susceptible to thrombotic
      events, is extremely important.

PMID- 11954889
TI  - Palmar fasciitis and arthritis: association with endometrial adenocarcinoma.
AB  - A 74-year-old woman was referred because of rheumatic symptoms consisting of
      pain, swelling of the hands, contracture and flexion of the fingers and severe
      palmar erythrosis. One year earlier she had undergone a total abdominal
      hysterectomy (TAH) for uterine adenocarcinoma. A paraneoplastic syndrome with
      palmar fasciitis and arthritis was then suspected and an evolutive peritoneal
      carcinomatosis was confirmed by abdominal CT scan. The patient was first treated
      with hormonal therapy (progestagen) and then with chemotherapy. This, associated
      with calcitonin, corticosteroids and physiotherapy, allowed a temporary recovery,
      but the patient died 10 months later from progressive peritoneal carcinomatosis.

PMID- 11954890
TI  - Calciphylaxis in a patient with rheumatoid arthritis without renal failure and
      hyperparathyroidism: the possible role of long-term steroid use and protein S
      deficiency.
AB  - Calciphylaxis is a rare and life-threatening condition of progressive cutaneous
      necrosis secondary to small and medium-sized vessel calcification that is seen
      almost exclusively in patients with end-stage renal disease and
      hyperparathyroidism. We report a case of calciphylaxis that may very well be due
      to a long-term steroid use in a rheumatoid arthritis patient who had neither end
      stage renal disease nor hyperparathyroidism. We also discuss the possible role of
      protein S deficiency as a contributing factor.

PMID- 11954891
TI  - Combined autoimmune disease in a patient with AIDS.
AB  - Immune dysregulation in HIV-infected patients, along with the new medications for
      treatment of AIDS that possess immunomodulating potential, may lead to an
      increased incidence of autoimmune diseases in this patient population. However,
      the presence of combined autoimmune diseases in an AIDS patient is rare.
      Relapsing polychondritis (RP) is an uncommon inflammatory disease manifested by
      recurrent attacks of auricular chondritis. The presence of type II and IX
      collagen antibodies, and their association with HLA-DR4 and other autoimmune
      diseases, suggests that antiself reactions may be present. Sarcoidosis is a
      granulomatous disease manifested by inflammation of the lungs, eyes and joints.
      In the peripheral blood there is depressed cellular immunity and enhanced humoral
      immunity. We here describe a case of coexisting RP and sarcoidosis in an AIDS
      patient.

PMID- 11954892
TI  - Mercury poisoning: an unusual cause of polyarthritis.
AB  - Mercury is a toxic metal that is widely used in everyday life. It has organic and
      inorganic forms that are both toxic. As acute mercury poisoning is uncommon,
      diagnosis is difficult if the exposure is not manifest. It has usually a slow
      onset and non-specific symptoms. In this paper we report a patient who developed
      polyarthritis after mercury exposure.

PMID- 11954893
TI  - Rheumatoid syndrome associated with lung interstitial disorder in a dental
      technician exposed to ceramic silica dust. A case report and critical literature
      review.
AB  - Exposure to silica minerals is associated with silicosis and autoimmune
      disorders, especially systemic scleroderma. Evidence of this association has been
      increasingly reported in the last decade. The aim of this paper is to discuss, on
      the basis of a literature review, the case of a 28-year-old female dental
      technician who suffered from episodes of weakness, arthralgia, pain, swelling and
      stiffness of the fingers, dyspnoea with cough, a positive Waaler-Rose reaction,
      increased rheumatoid factor and normal ESR. She was a non-smoker. A rheumatoid
      syndrome with lung interstitial disorder, associated with silica exposure from
      dental ceramic products, was diagnosed. The patient had the HLA-A2-A31, HLA-B51
      B18 and HLA-DR3-DR11 haplotypes, some of which are associated with autoimmune
      disease susceptibility. A 6-month follow-up, with adequate protection and without
      treatment, showed disappearance of the symptomatology and negative tests for
      Waaler-Rose reaction and rheumatoid factor. Exposure to silica should, therefore,
      be sought in the history of any patient with autoimmune or lupus-like syndrome
      and pulmonary changes. Symptoms associated with silica dust exposure from dental
      ceramic products should be recognised as being due potentially to an occupational
      disease, and dental technicians should be protected as workers at risk.

PMID- 11954894
TI  - Hyperviscosity syndrome in rheumatoid arthritis with Felty's syndrome: case
      report and review of the literature.
AB  - Hyperviscosity syndrome (HVS) is characterised by high serum viscosity and the
      involvement of multiple organs, commonly causing retinal haemorrhage, bleeding
      diathesis, pulmonary hypertension, congestive heart failure (CHF), neurologic
      deficits and death. It has been reported that HVS is mostly encountered in
      Waldenstrom's macroglobulinaemia (80%-90% of all HVS cases) and occasionally in
      multiple myeloma. HVS in patients with connective tissue diseases (CTD) has
      rarely been reported. Of 28 cases of HVS reported in patients with CTD, 19 were
      with seropositive rheumatoid arthritis (RA). However, only six of these 19 cases
      had Felty's syndrome. Here we report another case of HVS in a patient with RA as
      well as Felty's syndrome.

PMID- 11954895
TI  - Emergence of rheumatoid arthritis (RA) in the black peoples of Africa.

PMID- 11954896
TI  - Autoimmune-associated haemophagocytic syndrome in a patient with rheumatoid
      arthritis.

PMID- 11954898
TI  - Buprenorphine treatment of patients with non-malignant musculoskeletal diseases.
AB  - Adequate pain control is vital in the treatment of patients with musculoskeletal
      disease. These diseases are characterised by a number of pain-induced vicious
      circles, and satisfactory control of pain acts to disrupt these self-perpetuating
      processes. Consequently, early mobilisation can be achieved in patients with
      painful osteoporotic vertebral fractures, low back pain and sciatica, for
      example. In other cases analgesics may act simply to maintain the mobility of
      patients and in this way preserve their quality of life. When simple analgesics
      are not sufficient, the use of opioid-type analgesics is justified. Buprenorphine
      transdermal therapeutic system (TDS) is a novel formulation of a well-tolerated
      and highly effective drug for satisfactory pain control that can also be used in
      patients with chronic non-malignant pain (CNMP) due to musculoskeletal diseases.
      Three case reports are presented to illustrate the effectiveness of buprenorphine
      TDS in such patients.

PMID- 11954897
TI  - Buprenorphine in a transdermal therapeutic system--a new option.
AB  - Advanced patch technology has yielded a novel transdermal therapeutic system
      (TDS) for the rate-controlled systemic delivery of buprenorphine. Buprenorphine
      TDS is available in three strengths with release rates of 35, 52.5 and 70
      microg/h over 72 h, corresponding to daily doses of 0.8, 1.2 and 1.6 mg,
      respectively. In total, 445 patients with chronic pain of malignant or non
      malignant origin requiring long-term treatment with potent opioid analgesics were
      enrolled in the clinical trial programme. The patients were treated with
      buprenorphine TDS in one of three dosage strengths or with placebo TDS in a
      randomised double-blind setting. Greater pain relief was documented in patients
      treated with buprenorphine TDS than in those treated with placebo. The benefit of
      buprenorphine TDS was further reflected in the larger number of patients who
      slept for longer than 6 h per night. Patients switching from Step 2 or Step 3
      opioids to buprenorphine TDS encountered no problems with the conversion. Typical
      opioid-related adverse events were reported with a low incidence and mild
      intensity. In an open follow-up study 239 patients elected to continue treatment
      with buprenorphine TDS. The confirmation of clinical benefit, coupled with a high
      level of patient compliance and improved quality of life, substantiate the
      usefulness of buprenorphine TDS in a practical setting.

PMID- 11954899
TI  - Musculoskeletal pain and its socioeconomic implications.
AB  - Pain is the most common reason for patients seeking advice from their physician.
      One adult in five suffers from chronic pain. In general, musculoskeletal pain,
      often in the form of arthritis, non-articular rheumatism, peripheral neuropathies
      and low back disorders, represents the most common cause of chronic non-malignant
      pain (CNMP). Exposure to low social support, low social anchorage or low social
      participation significantly increases the odds of a high level of pain. Most
      patients do not attribute chronic musculoskeletal pain to injury, but those who
      do report significantly higher levels of emotional distress. Pain is the third
      leading reason for absence from work in the United States, where the problem of
      chronic pain translates into an annual expenditure of at least $50 billion. The
      effectiveness of opioids for chronic pain goes unchallenged, but issues of
      potential dependence, abuse, and social and legal concerns have rendered their
      use in CNMP controversial. Numerous consensus statements, guidelines and policies
      have been issued by a variety of advocate organisations for the treatment of CNMP
      with opioids. Undertreatment of chronic pain persists despite the availability of
      drugs and other therapies for effective pain management.

PMID- 11954900
TI  - Individual choice of opioids and formulations: strategies to achieve the optimum
      for the patient.
AB  - The role of opioid therapy in chronic musculoskeletal disease continues to be
      controversial. However, recent years have seen a gradual shift towards the use of
      opioid therapy in chronic non-malignant pain (CNMP) following recognition that at
      least a subpopulation of such patients appears to benefit from long-term opioid
      treatment. Misconceptions about opioids and the associated risk of dependence
      stemmed from older research that was fundamentally flawed. More recent, rigorous
      research has yielded clearer statistics on opioid dependence and has highlighted
      the need for screening to identify individuals who may require closer monitoring
      during long-term opioid therapy. Controlled-release formulations (oral and
      transdermal) for the management of steady pain, in conjunction with fast-acting,
      immediate-release formulations for the management of breakthrough pain, may be
      available for a wide range of opioid analgesics, providing comprehensive therapy
      systems for use in CNMP. However, there are no universal criteria that can be
      confidently used to select CNMP patients who might profit from or be responsive
      to opioid therapy. Opioid treatment must therefore be individualised for each
      patient, based on a clear understanding of drug absorption, metabolism, toxicity
      and binding characteristics, using opioid switching strategies where appropriate.
      Practical guidelines for opioid therapy in CNMP include regular and systematic
      checks of treatment results to adjust therapy for each individual patient and to
      ensure optimum benefit.

PMID- 11954901
TI  - Tramadol in musculoskeletal pain--a survey.
AB  - The three-step analgesic ladder, originally proposed for cancer pain relief by
      the World Health Organization (WHO), is now widely employed for all types of
      pain, including the chronic pain of musculoskeletal disease. Tramadol, an
      analgesic with weak opioid receptor affinity and possessing monoaminergic
      activity, has proved suitable for use at Step 2 of the WHO ladder. Owing to its
      pharmacological properties, tramadol is more appropriate than NSAIDs for patients
      suffering from gastrointestinal and renal problems. Importantly, the analgesic
      potency of tramadol is greater than that of NSAIDs and of other weak opioids
      (codeine, dextropropoxyphene). It also causes fewer opioid-type adverse effects,
      e.g. nausea, drowsiness, vomiting, dry mouth and constipation. In chronic
      musculoskeletal pain it is recommended that tramadol should be given by mouth and
      by the clock; the initial dose should be titrated upward gradually to reach the
      individual level required for suitable pain control. This dosage strategy will
      also minimise the usual opioid-type adverse effects encountered with tramadol.
      Four recent publications are reviewed to illustrate the efficacy of tramadol,
      alone or in conjunction with an NSAID, in the management of low back pain,
      osteoarthritis pain and breakthrough pain.

PMID- 11954902
TI  - Dirofilaria immitis: further characterization of the transglutaminase enzyme and
      its role in larval molting.
AB  - We recently reported the cDNA cloning and functional characterization of a novel
      transglutaminase (TGase) from the dog filarial parasite Dirofilaria immitis. D.
      immitis TGase (DiTG) has no sequence similarity with any other known TGase, but
      has significant similarity to protein disulfide isomerase (PDI)-related
      endoplasmic reticulum protein ERp60. In the present study. we further
      characterized the recombinant DiTG (rDiTG) and studied its role in the molting
      process of third-stage larvae. The enzymatic activity of rDiTG requires Ca2+, and
      the maximum activity was observed at a calcium concentration of 4 mM.
      Interestingly, the rDiTG was highly thermostable, with optimal activity observed
      at 55 degrees C, similar to that seen with the native enzyme. Dithiothreitol
      (DTT) was not essential for enzyme activity. In fact, rDiTG was more active in
      the absence of DTT. The known inhibitors of TGase, such as monodansylcadaverine
      (MDC), cystamine and iodoacetamide, inhibited the TGase activity, but not the PDI
      activity, of rDiTG, demonstrating the dual activity of rDiTG. The TGase-specific
      pseudosubstrate, MDC, completely inhibited the molting of D. immitis L3 to L4 if
      present during the first 24-48 h of the molting process. Electron microscopic
      studies revealed that MDC-treated infective larvae failed to show separation
      between the L3 and L4 cuticles. The L4 cuticle and accompanying hypodermis were
      much thinner in MDC-treated worms than in controls. Using anti-rDiTG antiserum,
      the native DiTG antigen was localized in the hypodermis, afibrillar muscle cells
      and gut epithelium in adult male and female worms as well as developing embryos
      in the females.

PMID- 11954903
TI  - Immunosuppressive effects of ixodes ricinus tick saliva or salivary gland
      extracts on innate and acquired immune response of BALB/c mice.
AB  - Saliva and salivary gland extract (SGE) of Ixodes ricinus ticks have suppressive
      effects on the innate immune response of BALB/c mice. Tick saliva prevents
      hemolysis of sheep red blood cells (SRBC) by the human alternative pathway of
      complement. The adaptive immune response is also modulated by tick antigens
      (saliva or SGE). When stimulated in vitro with increasing doses of tick antigens,
      the proliferation and IL-4 production of draining lymph node T cells of mice
      infested with nymphal ticks increase, peak and then decrease. These results
      indicate that immunostimulative and immunosuppressive molecules have competing
      effects in tick saliva or in SGE. I. ricinus saliva inhibits, in a dose-dependent
      manner, splenic T cell proliferation in response to concanavalin A (ConA). Tick
      SGE or saliva injected intraperitoneally to BALB/c mice simultaneously with SRBC
      systemically immunosuppress the anti-SRBC response as shown in vitro by the
      reduced responsiveness of sensitized splenic T cells to restimulation with SRBC.
      In brief some components of SGE or tick saliva reduce the responsiveness of
      draining lymph node T cells and of sensitized splenic T cells in vitro. The
      responsiveness of naive splenic T cells to ConA stimulation in vitro is also
      decreased by tick saliva. Modulation of host responses by tick antigens may
      facilitate tick feeding, transmission and the propagation of pathogens.

PMID- 11954904
TI  - Comparative ultrastructure of the actinosporean stages of Myxobolus bramae and M.
      pseudodispar (Myxozoa).
AB  - The ultrastructrure of triactinospores and other developmental stages obtained
      after the experimental infection of the oligochaete Tubifex tubifex with
      myxospores of Myxobolus bramae and Myxobolus pseudodispar was studied. In both
      cases, pansporocysts harbouring spores and the remnants of polar bodies were
      found in the gut epithelium of the tubificids. Other stages were also seen in M.
      pseudodispar. Capsulogenic cells surrounded the apical part of the sporoplasm in
      M. bramae whereas they were located separately in M. pseudodispar. The sporoplasm
      of M. bramae was elongated and was filled with numerous infective cells, whereas
      secondary cells rarely appeared in the sporoplasm of M. pseudodispar, which
      contained large groups of beta-glycogen granules. Other M. pseudodispar stages
      included pansporocysts harbouring pregametic or gametic stages, zygotes, or the
      initial steps of sporogenesis. The presence of first- and second-order polar
      bodies indicates the existence of meiosis. In the spores of M. pseudodispar, the
      presence of desmosome-like junctions between the capsulogenic cells, and
      hemidesmosome-like junctions between the capsulogenic cells and the inner
      membrane of the valvogenic cells, is remarkable.

PMID- 11954905
TI  - Involvement of secretory and cytosolic phospholipases A2 during infection of THP1
      human monocytic cells with Toxoplasma gondii. Effect of interferon gamma.
AB  - Toxoplasma gondii is an intracellular, obligate protozoan parasite that actively
      invades host cells. Phospholipases A2 (PLA2) are widely distributed enzymes that
      exist in many isoforms [secretory (sPLA2), cytosolic (cPLA2)] in monocytic and
      other human cells (pancreatic, kidney, etc) and also in parasites. We examined
      the effects of inhibitors of sPLA2 type II and cPLA2 on the invasion of human
      monocytic cells (THP1) by T. gondii (RH strain). We also measured sPLA2 type II
      and cPLA2 enzyme activities and their modulation by interferon gamma (IFN gamma)
      in extracts of host cells and parasite. Inhibition of both parasite and THP1
      sPLA2 type II, and of parasite cPLA2 reduced the number of infected cells. Enzyme
      assays and immunoblot analyses demonstrated T. gondii sPLA2 type II and cPLA2
      activities and indicated that T. gondii increased the activity of THP1 sPLA2 type
      II. Incubation with IFN gamma (1,000 units/ml) for 20 h reduced the activities of
      sPLA2 and cPLA2 in infected and non-infected cells. Thus, IFN gamma blocks the
      activities of both THP1 and parasite sPLA2 and cPLA2 in membrane fractions,
      resulting in protection against active invasion by T. gondii.

PMID- 11954906
TI  - Monoclonal antibodies specific for the two types of wall-forming bodies of
      Eimeria tenella macrogametes (Coccidia, Apicomplexa).
AB  - Two monoclonal antibodies (mAbs) raised against the macrogamonts of Eimeria
      tenella identified antigens located in the wall-forming bodies of type I (WF I)
      and type II (WF II) by indirect immunofluorescence and by immunoelectron
      microscopy. With these mAbs, the involvement of both types of wall-forming body
      at the protein level in the formation of the inner and outer oocyst walls of E.
      tenella was shown by indirect immunofluorescence assay. On Western blots of pure
      macrogamont, mAb E1D8 against WF I reacted with a series of bands between 42 kDa
      and 105 kDa. In pure, unsporulated extract, this mAb recognized a complex of
      bands between 26 kDa and 153 kDa. mAb E2E5 against WF II, on Western blots of
      pure extract of macrogamonts, recognized an antigen of 51 kDa. Later in the
      development, after the formation of the inner oocyst wall, mAb E2E5 reacted with
      three polypeptide of 23, 25 and 30 kDa. Proteolytic processing may be forwarded
      as the mechanism regulating the distinct regulation protein involved in the
      oocyst wall.

PMID- 11954907
TI  - Effects of mercury and chromium upon longevity of Diplostomum sp. (Trematoda:
      Diplostomidae) cercariae.
AB  - Laboratory experiments were carried out to examine the impact of mercury and
      chromium upon survival of Diplostomum sp. cercariae. Freshly emerged cercariae
      were exposed to solutions of either mercury, at concentrations ranging between
      0.1 and 100 microg/l, or chromium at concentrations from 2 microg/l to 2 mg/l.
      The mortality patterns and mean survival times (MSTs) of the exposed parasites
      were determined by the Kaplan-Meier estimator and were compared (log-rank test)
      with corresponding patterns and estimators of the unexposed controls. Mercury
      concentrations > or = 10 microg/l caused statistically significant changes in the
      mortality pattern of Diplostomum sp. cercariae and reduced MST by at least 9 h
      compared with the control group, in which MST was 42 h. Cercariae exposed to
      chromium solutions had statistically significant changes in mortality pattern
      only at a concentration of 2 mg/l and exhibited a reduction in MST of 8 h
      compared with the control (MST = 41 h). The results show for the first time that
      longevity of Diplostomum sp. cercariae can be reduced by direct exposure to heavy
      metals. Ecotoxicological effects of mercury are manifested at lower
      concentrations than those of chromium, and thus potentially have a higher impact
      on parasite populations and communities.

PMID- 11954908
TI  - Species diversity among the genus Monorchis (Digenea: Monorchiidae) parasitic in
      marine teleosts: molecular, morphological and morphometrical studies with a
      description of Monorchis blennii n. sp.
AB  - Molecular, morphological and morphometrical studies were conducted on two species
      of the genus Monorchis (Monorchiidae), Monorchis parvus and Monorchis monorchis,
      collected in different fish hosts from the Mediterranean Sea. The analysis of
      internal transcribed spacer 1 sequences of ribosomal DNA showed that M. monorchis
      specimens from Parablennius gattorugine were strongly divergent (12.9%) from
      specimens of this species collected in Spondyliosoma cantharus and Diplodus
      puntazzo. This high genetic variation was confirmed by the analysis of
      morphological structures and morphometrics, which showed that M. monorchis
      specimens from P. gattorugine can be distinguished from those of S. cantharus and
      D. puntazzo by several morphological characteristics, including body size, number
      and distribution of vitelline follicles, testis shape, structure of the cirrus
      pouch, and number of eggs. Our results show that M. monorchis specimens isolated
      from P. gattorugine represent a clearly distinct entity from M. monorchis found
      in the other hosts, which has enabled us to describe a new species, Monorchis
      blennii n. sp.

PMID- 11954909
TI  - Scratching the sporocyst surface: characterisation of European Aggregata species
      by atomic force microscopy.
AB  - The application of atomic force microscopy to the understanding of surface
      structure and atomic-scale measurements on the sporocyst of European Aggregata
      species, intracellular coccidia of the cephalopods Octopus vulgaris and Sepia
      officinalis, is presented here. Using the roughness mean surface (RMS) as an
      index, we reveal texture to be a key parameter for characterisation of the
      sporocyst surface properties, which resolve the historical synonymy within the
      European Aggregatidae. Roughness measurements from RMS algorithms may also be an
      important diagnostic taxonomic character for the differentiation of Aggregata
      species in the future.

PMID- 11954910
TI  - Low intraspecific variation in the rRNA internal transcribed spacer 2 (ITS2) of
      the Australian paralysis tick, Ixodes holocyclus.
AB  - Ixodes holocyclus has a narrow, discontinuous distribution along the east coast
      of Australia. We studied ticks from 17 localities throughout the geographic range
      of this tick. The ITS2 of I. holocyclus is 793 bp long. We found nucleotide
      variation at eight of the 588 nucleotide positions (1.4%) that were compared for
      all ticks. There were eight different nucleotide sequences. Most sequences were
      not restricted to a particular geographic region. However, sequences F, G and H,
      which had an adenine at position 197, were found only in the far north of
      Queensland--all other ticks had a guanine at this position. The low level of
      intraspecific variation in this tick (0.7%) contrasts with the sequence
      divergence between I. holocyclus and its close relative, I. cornuatus (13.1%).
      These data indicate that I. holocyclus does not contain cryptic species despite
      possible geographic isolation of some populations. We conclude that variation in
      the ITS2 is likely to be informative about the phylogeny of the group.

PMID- 11954911
TI  - Traffic pathways of Plasmodium vivax antigens during intraerythrocytic parasite
      development.
AB  - We investigated the secretory traffic of a Plasmodium vivax antigen (Pv-148)
      synthesised by the parasite during the blood cycle, exported into the host cell
      cytosol and then transported to the surface membrane of the infected erythrocyte.
      Studies of the ultrastructure of erythrocytes infected with P. vivax showed that
      intracellular schizogony is accompanied by the generation of parasite-induced
      membrane profiles in the erythrocyte cytoplasm. These structures are detectable
      soon after the parasite invades the erythrocyte and develop an elaborate
      organisation, leading to a tubovesicular membrane (TVM) network, in erythrocytes
      infected with mature trophozoites. Interestingly, the clefts formed stacked,
      flattened cisternae resembling a classical Golgi apparatus. The TVM network
      stained with the fluorescent Golgi marker Bodipy-ceramide. Specific
      immunolabelling showed that Pv-148 was transferred from the parasite to the
      erythrocyte surface membrane via the clefts and the TVM network. These findings
      suggest that the TVM network is part of the secretory pathways involved in
      parasite protein transport across the Plasmodium-infected erythrocyte and that Pv
      148 may represent a marker that links the parasite with the host cell cytoplasm
      and, in turn, with the extracellular milieu.

PMID- 11954912
TI  - Helminth fauna of the European polecat (Mustela putorius Linnaeus, 1758) in
      Belorussian polesie.

PMID- 11954913
TI  - Individual cases of autochthonous malaria in Evros Province, northern Greece:
      serological aspects.
AB  - From 1994 to 1995 four presumably autochthonous malaria cases were diagnosed by
      blood smear microscopy in Evros Province, northern Greece. Alarmed by these
      unexpected infections a serological survey was performed from 1997 to 1999 in ten
      rural villages, including those where the malaria cases had occurred. Among the
      1,102 blood samples examined, nine turned out to contain specific antibodies
      against plasmodial parasites as detected by indirect fluorescent antibody test,
      including two of the former patients. The remaining seven samples were taken from
      healthy individuals with no history of recent infection or of having travelled to
      endemic areas. A further 21 sera showed borderline reactivity with Plasmodium
      falciparum antigen. Although no retrospective examination of the blood specimens
      could be performed to confirm the serological results by direct parasite
      detection, we can conclude that at least the seropositive persons have actually
      undergone infection with malaria parasites but developed no or only mild clinical
      symptoms which went unnoticed. It is becoming obvious that even in European
      countries where climatic and vector conditions are favourable for the development
      of the parasite there is a potential risk of incidental malaria transmission by
      indigenous Anopheles mosquitoes.

PMID- 11954914
TI  - Expression of housekeeping genes during the asexual cell cycle of Plasmodium
      falciparum.
AB  - In an earlier study, we found that calmodulin displayed an atypical expression
      for a housekeeping gene during the erythrocytic cycle of Plasmodium falciparum.
      The expression pattern was that of an inducible gene linked to the cell cycle,
      with a peak prior to replication, and not one of a gene that expresses itself in
      a constitutive way. In this work, we examined the expression pattern of other
      housekeeping genes, selecting genes from two functionally very different groups:
      those for three enzymes involved in carbohydrate metabolism--glucose-phosphate
      isomerase (GPI), aldolase and glucose-6-phosphate-dehydrogenase (G6PD)--and for
      three proteins with structural and motor functions--actin-I, beta-tubulin and
      myosin. The mRNA of each gene was measured by reverse transcription-polymerase
      chain reaction in synchronic parasite samples that were 14, 28, 40 and 48 h old.
      GPI and G6PD achieved their maximum expression at 28 h, then declined, while
      aldolase increased its expression up to 40 h and remained high, but less so at 48
      h. Actin and myosin showed the same pattern, increasing up to 48 h, while beta
      tubulin expression peaked at 40 h. These findings confirm unconventional behavior
      in the expression of certain Plasmodium housekeeping genes and suggest the
      existence of different expression patterns for distinct functional groups.

PMID- 11954915
TI  - Chemotherapeutic approaches to nematodes: current knowledge and outlook.
AB  - The situation in the chemotherapy of nematode infections. in both human and
      veterinary medicine, is currently satisfactory. There are different drugs
      available: the benzimidazoles, levamisole, pyrantel, and the different
      macrocyclic lactones (Tables 1. 2, 3, 4). In human medicine, mebendazole and
      albendazole are mainly used against the intestinal nematodes. while ivermectin
      and diethylcarbamazine are microfilaricidal drugs used in prophylaxis against
      onchocercosis and filarial infections. The situation in veterinary medicine is,
      however, governed by the great resistance problem in some animal hosts against
      all important anthelmintics. There are various reports of resistance against
      benzimidazoles, levamisole, pyrantel, and macrocyclic lactones in
      trichostrongylides in small ruminants (sheep, goats) and also Strongylides in
      horses. Resistance against ivermectin is now arising in cattle (Coles 2001;
      Sangster 2001). There are no reports of resistance problems in dogs and cats.
      Thus, there is always an urgent need in veterinary medicine for new anthelmintics
      with a new mode of action, which can easily break resistance against the existing
      anthelmintics. The situation in the chemotherapy of filarial infections in human
      medicine is not satisfactory. There is an urgent need for a new macrofilaricidal
      drug with only slight side-effects. Today, the only way is the prophylactic
      control of Onchocerca vovulus infections and treating lymphatic filariosis with
      ivermectin, diethylcarbamacine, ivermectin/diethylcarbamazine. or
      ivermectin/albendazole combinations.

PMID- 11954916
TI  - Field observations on the phlebotomine sand fly Australophlebotomus mackerrasi
      Lewis and Dyce feeding on the Gidgee skink Egernia stokesii Gray.

PMID- 11954917
TI  - The taenia solium glucose transporters TGTP1 and TGTP2 are not immunologically
      recognized by cysticercotic humans and swine.
AB  - Cysticercosis caused by the metacestode of the tapeworm Taenia solium causes
      economic losses in pork meat production, as well as being a human health hazard
      in some parts of the world. In order to determine if the glucose transporters
      TGTPI and TGTP2 are recognized by antibodies in the sera from cysticercotic
      humans and pigs, western blot assays were carried out using membrane fractions of
      insect cells expressing the two T. solium glucose transporters. Results
      demonstrated a complete lack of recognition of both TGTPs. These results are
      unexpected, because at least one transporter is present on the apical surface of
      the cysticercus tegument.

PMID- 11954918
TI  - Botulinum toxin for dysphagia due to cricopharyngeal dysfunction.
AB  - Botulinum injection in the cricopharyngeal muscle has not yet been described
      thoroughly. In reviewing the literature, only 24 cases were found in which
      botulinum injection was used to treat cricopharyngeal dysfunction. We want to add
      another four cases and discuss specific indications and necessary pre-treatment
      examinations. Depending on the patient's history and the clinical findings,
      botulinum injection may be performed. Manometry and videofluoroscopy are not
      mandatory. The type of functional pathology defines whether botulinum toxin will
      be a definite treatment or a temporary relief.

PMID- 11954919
TI  - Quality of life after conservative laryngeal surgery: a multidimensional method
      of evaluation.
AB  - Assessment of quality of life (QoL) and satisfaction with care are particularly
      important in the field of oncology. The definition of QoL and the requirements
      for its measurement are still a matter of debate, but it is generally accepted
      that QoL is a multidimensional concept involving three different domains:
      physical, psychological and social. The aim of this study was to test a simple,
      inexpensive, multidimensional method of QoL measurement, based both on patients'
      perception of clinical outcome and the quantitatively evaluated clinical outcome,
      equally weighted, in patients who underwent three different types of conservative
      laryngeal surgery: horizontal laryngectomy (HG), supraglottic laryngectomy (SL)
      and subtotal reconstructive laryngectomy (SRL). The following were carried out
      for each patient: subjective-objective evaluation of speech [computerized
      spectrographic analysis of fundamental frequency (FO), percentage of noise and
      intensity and logopedic evaluation of speech], evaluation of deglutition
      (videofluoroscopic parameters, and qualitative assessment) and evaluation of
      physical, social, emotional and functional well-being (Functional Assessment of
      Cancer Therapy, FACT-G, and modified University of Washington Quality of life
      Scale, UWQoL). Each assessment was given a score rating from one to three points.
      The overall evaluation of the qualitative and quantitative score for each field
      and for each type of laryngeal surgery shows that SL results in the best post
      operative QoL. Although HG is less damaging and involves swifter functional
      recovery times, its slightly lower score is due to the poorer quality of speech.
      The analysis of the results obtained confirm the need to set up an evaluation
      protocol combining both the subjective perceptions of the patient, as well as the
      more objective evaluation of the functions that are impaired following surgery.
      The protocol described above, although limited by the low number of cases, was
      easy to carry out, inexpensive and applicable in relation to the various types of
      surgery that may compromise phonation and deglutition.

PMID- 11954920
TI  - Cochlear ultrastructure in two-phase endolymphatic hydrops in the guinea-pig.
AB  - Endolymphatic hydrops continues to be considered as a pathological factor in the
      etiology of Meniere's disease. We have developed the two-phase endolymphatic
      hydrops model, which seems to represent a functional model combining multiple
      etiologies, and which may resemble the fluctuating characteristics of Meniere's
      disease. A transmission electron microscopic study was performed on the
      endolymphatic sacs of four groups of guinea-pig cochleas: (1) controls, (2) non
      operated, aldosterone-treated cochleas, (3) operated (dissection of the
      endolymphatic sac) cochleas, (4) operated and aldosterone-treated cochleas. Light
      and electron microscopy showed a normal morphology in the controls. Aldosterone
      as a single treatment resulted in an increased activity of the marginal cells in
      the stria vascularis. Dissection induced a gradient of degenerative effects and
      cell loss in the intracellular and extracellular structures of the sensory cells,
      the stria vascularis and Reissner's membrane, which may be reversible. Subsequent
      administration of aldosterone induced severe damage and increased cell loss,
      which may be irreversible. Our findings demonstrate changes that may be
      reversible due to the compromising effect of a single treatment, and irreversible
      changes due to interaction of both compromising factors. These findings support
      our two-phase concept.

PMID- 11954921
TI  - Vestibular evoked myogenic potentials in patients with contralateral delayed
      endolymphatic hydrops.
AB  - We studied vestibular evoked myogenic potentials (VEMPs) in nine patients with
      unilateral profound hearing loss followed by contralateral delayed hearing
      fluctuation and episodic vertigo. This condition has been called contralateral
      delayed endolymphatic hydrops. Five of nine ears with profound hearing loss (56%)
      showed an absence of VEMPs. One ear (11%) showed decreased responses, and three
      ears (33%) had normal responses. Of the ears with fluctuation of hearing, six
      (67%) showed an absence of responses, and three ears (33%) showed normal
      responses. In four patients we recorded VEMPs before and after oral
      administration of glycerol. Three hours after glycerol administration, two of
      four ears with fluctuating hearing loss showed the appearance of VEMPs although
      there was an absence of VEMPs before glycerol administration. These results
      suggested that saccular dysfunction could exist not only in the ears with
      profound hearing loss but also in ears with fluctuating hearing loss and that
      saccular endolymphatic hydrops could exist in the ears with fluctuating hearing
      loss. "Contralateral delayed endolymphatic hydrops" might be an appropriate term.

PMID- 11954922
TI  - Tumor oxygenation under combined whole-body-hyperthermia and polychemotherapy in
      a case of recurrent carcinoma of the oral cavity.
AB  - BACKGROUND: Previous studies have reported synergistic effects of combined
      hyperthermia and chemotherapy and/or irradiation. The discussed underlying
      mechanism for this effect is an synergistic cytotoxic and radiosensitizing effect
      of hyperthermia. In addition, tumor blood-flow and, consequently, tumor
      oxygenation are increased during hyperthermia. Tumor response to irradiation and
      chemotherapy of well-oxygenated and vascularized tumors, in general, is superior
      to that of hypoxic tumors. Therefore, tumor oxygenation is recognized as an
      important predictive factor in the therapy of malignant tumors. Technically, the
      head-neck area remains outside the hyperthermia chamber during whole-body
      hyperthermia (WBH) as currently applied in a number of cancer treatment regimens.
      The aim of this therapeutic approach was to evaluate whether the blood flow
      during WBH also increased in the head-neck region and, if so, whether tumor
      oxygenation increase accordingly. METHODS: A 60-year-old male Caucasian patient,
      with the original diagnosis of pT3 pN2b M0 squamous cell carcinoma of the oral
      cavity, who had undergone primary surgery and irradiation (total dose 60 Gy),
      developed three local recurrences with consecutive surgical resection, presenting
      now with another recurrent local tumor (histologically confirmed) without
      surgical or radiotherapeutical options due to lymphangiosis carcinomatosa. WBH
      was applied under full anaesthesia, using a humidified radiant heat device
      (Enthermics Medical Systems RHS-7500) in combination with synchronous application
      of chemotherapy (ifosfamide and carboplatin). Four cycles of this combined
      treatment (one cycle per month) were given. Tumor oxygenation and temperature
      were continuously monitored by Licox catheters by means of one point measurement
      during each treatment (3.5 h). RESULTS: With a latency of 10 min, the increase of
      intratumoral temperature in the oral cavity was comparable to reference values in
      the esophagous. Maximum intratumoral temperature (oral cavity) was 41.8 degrees C
      (F). The average increase of tumor oxygenation was more than 100% in each
      individual cycle. Clinically, a partial tumor response was observed. CONCLUSIONS:
      During combined WBH and polychemotherapy, oxygenation is also significantly
      improved in a tumor in the head and neck area despite the fact that head and neck
      area remains outside the hyperthermia chamber during WBH. Intratumoral
      temperatures achieved are comparable to esophageal and rectal temperatures
      obtained during WBH.

PMID- 11954923
TI  - Results of an organ preservation protocol with induction chemotherapy and
      radiotherapy in patients with locally advanced pyriform sinus carcinoma.
AB  - An alternative to the classical treatment for locally advanced (T3-T4 stage)
      pyriform sinus carcinoma with surgery and postoperative radiotherapy is to begin
      treatment with induction chemotherapy in an organ preservation approach. In
      patients with complete clinical response, this treatment is followed by
      radiotherapy; in noncomplete responders, it is followed by surgery and
      postoperative radiotherapy. We conducted a retrospective study to evaluate such
      treatment in a cohort of 78 patients with locally advanced pyriform sinus
      carcinoma treated at a single institution between 1985 and 1997. In all patients,
      induction chemotherapy with cisplatin and 5-fluoruracil was carried out. Two
      patients died as a consequence of complications associated with chemotherapy
      treatment. Of the 76 patients who completed treatment, 23 (30%) achieved a
      complete response at the primary site, 38 (50%) attained a partial response, and
      15 patients (20%) had a stabilization-progression. The 5-year adjusted survival
      of patients treated with radiotherapy alone was 57% and, in patients treated with
      surgery, 51%. There were no significant differences in survival related to the
      subsequent treatment used (P > 0.05). The larynx was preserved in 14 of the 23
      patients (61%) who completed treatment with induction chemotherapy and
      radiotherapy. The frequency of organ preservation for the group of 78 patients
      who began treatment with induction chemotherapy was 18%.

PMID- 11954924
TI  - Delayed carotid artery rupture in advanced cervical cancer--a dilemma in
      emergency management.
AB  - Carotid artery rupture in the setting of advanced carcinoma of the head and neck
      constitutes a surgical emergency. This report details three such patients, two of
      whom presented with profuse bleeding, the other with imminent rupture. Notably,
      our first patient ruptured 27 years after having had radiotherapy for carcinoma
      of the larynx. This patient had had no previous surgery and at operation no
      recurrent tumor was evident. In the other two patients, previous surgery had
      demonstrated tumor invasion of the carotid artery. The choice of therapy in this
      calamitous condition is controversial, the question being whether to resect and
      reconstruct or ligate the ruptured artery. Our three patients underwent ligation
      with no recurrence of bleeding and no neurological sequelae for a follow-up
      period of 5-36 months. Of paramount importance is the hemodynamic stabilization
      of the patient prior to being submitted to surgery. Our results favor ligation
      rather than resection and reconstruction as the procedure of choice in this
      difficult predicament.

PMID- 11954925
TI  - How often is total laryngectomy necessary for the treatment of T1 failures after
      radiotherapy or cordectomy?
AB  - Between 1992 and 1998, 547 patients (pts) with laryngeal SCC were diagnosed and
      treated in our department, 145 (27%) of whom presented with glottic tumors T1N0M0
      (125 T1a and 20 T1b). Seventy-eight (54%) were treated surgically with cordectomy
      and 67 (46%) with radiotherapy. After a median follow-up time of 43 months, 22
      (15.2%) of the 145 pts presented with recurrent disease. In more detail, 16 (13%)
      of the 125 T1a pts and 6 (30%) of the 20 T1b pts had recurrences. Among the 78
      surgically treated patients only 4 (5%) had recurrence, while 18 (27%) of the
      radiotherapy group relapsed. The difference is statistically significant (log
      rank test, P = 0.0001 < 0.05). After salvage treatment, of the 67 pts of the
      radiotherapy group 57 (85%) remain disease-free, 49 (73%) retaining their larynx
      intact and 1 only having undergone cordectomy. Among the cordectomy group 75
      (96%) pts remain disease-free with only 1 having had a total laryngectomy. Using
      the Kaplan-Meier method and calculating the disease-free survival regardless of
      salvage treatment, there is no doubt that surgical treatment statistically is
      more successful than radiotherapy (log rank test, P = 0.01 < 0.05). Analysis of
      parameters such as tumor differentiation and T1a or T1b staging, which indeed
      influence the overall recurrence rate, did not alter the favorable outcome after
      surgical treatment.

PMID- 11954926
TI  - Decompression for Bell's palsy: why I don't do it.
AB  - All decompression surgery is based on the lack of understanding that Bell's palsy
      is a viral demyelinating disease that is longitudinal--not perpendicular--to the
      facial canal and that surgery cannot possibly help a viral disease. These
      findings exclude the etiologic possibility of an "ischemic paralysis" and are in
      accord with our logically derived belief that treatment directed to relieve
      neural entrapment is a wasted effort.

PMID- 11954927
TI  - The influence of early speech rehabilitation with voice prostheses on the
      psychological state of laryngectomized patients.
AB  - This survey assessed how early speech rehabilitation influences the emotional
      state and psychological adjustment of 43 male laryngectomy patients, at three
      different chronological stages. The first assessment occurred 2-3 days before the
      operation. The patients filled out a stress questionnaire (SVF) which assessed
      coping strategies. Exactly 2 weeks after the operation the patients were given a
      list of adjectives (EWL) which measured their actual emotional state. One day
      before leaving the hospital the patients were given the Post-laryngectomy
      Telephone Test (PLTT) which ascertained the quality of speech intelligibility. In
      addition, patients filled out a questionnaire on postoperative stress and
      anticipated stigmatisation with regard to their changed voice. Results
      demonstrated that patients who had early speech rehabilitation felt significantly
      more active and, in general, felt considerably better than patients who had not
      received speech rehabilitation training. Patients assessed voice loss as
      extremely distressing. The postoperative stress and the anticipated
      stigmatisation on the basis of the changed voice was significantly higher in
      those patients with good speech intelligibility than in patients with poor speech
      articulation at hospital discharge. The coping strategies "Giving up and
      resignation" and "Need for social support" correlated positively with
      postoperative stress and anticipated stigmatisation. Results show that early
      speech rehabilitation with voice prostheses had a positive effect on the
      emotional state of laryngectomy patients. However, the early speech
      rehabilitation leads to distress in the initial phase in laryngectomy patients.
      Moreover, patients who habitually tend towards resignation, or need lots of
      social support should receive psychological support during the early phase of
      speech rehabilitation training.

PMID- 11954928
TI  - Effect of atmospheric factors on the incidence of Bell's palsy.
AB  - To assess the possible influence of atmospheric factors on the incidence of
      Bell's palsy, a retrospective case review of patients seen between 1 January 1992
      and 30 June 1996, was designed. The population included all Bell's palsy patients
      in whom the exact date of onset of paralysis (day, month, year) was known. The
      following parameters were registered daily by the Spanish National Service of
      Meteorology throughout the period of survey: temperature, atmospheric pressure
      and air pollutants (total number of particles and levels of SO2, CO, O3, NO2, NO,
      CH4 and total organic carbon). The only factor significantly related to Bell's
      palsy was temperature (P = 0.0164). Lower temperatures were associated with a
      higher incidence of Bell's palsy. A relationship between atmospheric pressure
      and/or air pollutants and Bell's palsy was not found.

PMID- 11954929
TI  - Craniofacial characteristics and velopharyngeal function in cleft lip/palate
      children with and without adenoidectomy.
AB  - The association between velopharyngeal function, craniofacial morphology and
      adenoidectomy was investigated using 27 craniofacial and nasopharyngeal variables
      taken from lateral cephalograms. The sample consisted of 96 boys with cleft
      palates with or without cleft lips. They were examined at 6 years of age when
      cephalograms were obtained and perceptual speech assessments were performed. The
      subjects were divided into three groups: (1) velopharyngeal competence (VPC, n =
      45); (2) mild incompetence not requiring velopharyngoplasty (VPI, n = 36); and
      (3) previous incompetence operated on with velopharyngoplasty ad modum Hoenig
      (VPP, n = 15) before the 6-year examination. The groups were further divided into
      two subgroups according to previous adenoidectomy (Ad+, Ad-). The cranial base,
      size and interrelationship of the maxilla and mandible and their relationship to
      the cranial base or the bony nasopharynx did not differ among the VPC, VPI and
      VPP groups. The sagittal depth of the nasopharyngeal airway (Pm-ad1, Pm-ad2, Pm
      ad3) was significantly wider in the VPP group than in the the VPC and VPI groups.
      The previous adenoidectomy decreased the thickness of the posterior pharyngeal
      wall (ad1-Ba, ad2-so) and thus increased airway size. The length of the velum did
      not differ between the three groups or their subgroups with and without
      adenoidectomy. The results showed that adenoidectomy is a risk to velopharyngeal
      function by widening the nasal airway, but velopharyngeal incompetence cannot
      definitely be attributed to adenoidectomy.

PMID- 11954930
TI  - Dual ectopic thyroid.
AB  - Ectopic thyroid is an uncommon embryological aberration characterized by the
      presence of thyroid tissue in a site other than in its usual pre-tracheal region.
      It occurs along the path of descent of the developing thyroid primodium from the
      foramen cecum. It most commonly presents itself as a lingual thyroid and is the
      only thyroid in 70% of all cases. It is extremely rare for two ectopic foci of
      thyroid tissue to be present simultaneously. The authors report a recent case of
      dual ectopic thyroid present in the lingual and infrahyoid areas with no thyroid
      tissue in the pre-tracheal area in a 15-year-old girl. The patient had originally
      been scheduled for surgery under the impression of thyroglossal duct cyst;
      however, a pre-operative computed tomography scan of neck and thyroid scans
      revealed the presence of dual ectopic thyroid, thus preventing unnecessary
      surgery. Therefore, thyroid scan, along with either neck CT or neck
      ultrasonogram, should be performed routinely to avoid unnecessary surgery if the
      clinical picture is at all compatible with thyroid ectopia.

PMID- 11954931
TI  - Myotonometry demonstrates changes of lingual musculature in obstructive sleep
      apnoea.
AB  - Upper airway dilator muscles are important in the pathogenesis of obstructive
      sleep apnoea (OSA). Previously, soft palate and tongue muscles of patients with
      OSA have been studied from a histological point of view. Electromyographic
      studies revealed increased activity of upper airway dilator muscles. We used
      computerized endopharyngeal myotonometry (CEM) to measure the biomechanical
      properties of lingual musculature, mainly the genioglossal muscle, to
      characterize changes of tongue muscles in patients with OSAS. The method records
      and analyzes the response of the tongue sublingually after a brief mechanical
      impact. It enabled us to evaluate the most important parameters of tissue tone-
      stiffness, which is expressed as a frequency, and elasticity, as a logarithmic
      decrement of the damped oscillation. The results of CEM indicated that patients
      with OSAS show an increased stiffness (14.1 +/- 0.7 Hz) of the tongue in
      comparison with non-snoring subjects (11.5 +/- 0.2 Hz). The elasticity of the
      tongue is decreased, which is numerically expressed as an increased decrement
      (4.0 +/- 0.2) in patients with OSA in comparison with non-snorers (2.2 +/- 0.2).
      Changes in the biomechanical characteristics of lingual musculature during
      wakefulness could result from pathophysiological processes caused by obstructive
      sleep apnoea.

PMID- 11954932
TI  - Assessment of the results of glottis-dilating operations using lung function
      tests.
AB  - Our aim was to obtain an objective evaluation of the airway before and after
      glottis-dilating operations utilizing lung function tests. The charts of 109
      patients who underwent either reversible or irreversible glottis-dilating
      operations by Lichtenberger were reviewed. 64 nonselected cases of these
      patients, all with irreversible glottis-dilating operations, were studied. Lung
      function tests that were performed were body-pletysmography, forced inspiratory
      volume (FIV1), forced expiratory volume (FEV1), peak inspiratory flow rate (PIF),
      peak expiratory flow rate (PEF) and resistance of the airways (RAW). The FEV1,
      FIV1, PEF and PIF all improved following irreversible glottis-dilating
      operations. The RAW was remarkably decreased post-operatively as compared to pre
      operatively. In conclusion, the airways of patients undergoing irreversible
      glottis-dilation operations improved moderately to well following such surgeries.
      Lung function tests are an objective means of evaluating the airway before and
      after surgery.

PMID- 11954933
TI  - Dermoid cyst of the floor of the mouth--a case report.
AB  - We report a case of a 30-year-old, previously healthy man who presented at our
      clinic with complaints of increasing dysphagia and globus sensation for about 2
      years. In addition, he noticed an increasing submental swelling. On examination,
      the patient revealed a massive swelling of the floor of the mouth, which had
      displaced the tongue cranially. MRI imaging showed the lesion to be a
      homogeneous, cystic lesion, clearly at a distance from the surrounding mucous
      tissue. Surgery was performed, and the tumor was resected completely. Histologic
      examination of the resected tissue was consistent with a dermoid cyst located in
      the floor of the mouth. Although dermoid cysts are rarely located in the oral
      cavity, it should be included in differential diagnosis. Surgery is the treatment
      of choice.

PMID- 11954934
TI  - The effect on arterial blood gases and heart rate of bilateral nasal packing.
AB  - In order to elucidate the blood gas and heart rate changes caused by bilateral
      nasal packing, 21 healthy subjects who had had septoplasty or septorhinoplasty
      were investigated with pre- and post-operative blood gas measurements and 24-h
      Holter monitoring. Nasal packing caused a significant decrease in O2 saturation
      (P < 0.05), a borderline decrease in PO2 (P = 0.09), insignificant changes in
      PCO2, pH and HCO3 (P > 0.05), a significant increase in minimum and mean heart
      rates (P < 0.05) and insignificant changes in maximum heart rates; however,
      further research is necessary to elucidate the direct cause-and-effect
      relationship. No serious arrhythmias were observed. Although these changes may be
      within normal levels for healthy subjects, they may have serious consequences for
      patients with cardiopulmonary diseases.

PMID- 11954935
TI  - Purulent otitis media in children and adults.
AB  - This study was designed to compare tympanic membrane (TM) and middle ear (ME)
      pathologies of temporal bones from children and adults with purulent otitis media
      (POM). Thirty-four temporal bones were used from 22 subjects ages 2 days to 76
      years with histopathologic evidence of POM. There were 55 age-matched controls.
      Histopathologic findings of the TM and ME in children and adults with POM were
      compared. Clinical histories and the presence of complications were recorded. The
      incidence of POM was more common in male children than in females. There was a
      significant increase in the thickness of the posterosuperior and posteroinferior
      quadrants in children with POM compared to non-OM children. In adults with POM,
      there was a significant decrease in the thickness of the posteroinferior and
      anteroinferior quadrants compared to non-OM adults. Children with POM showed a
      significant increase in the anterioinferior and posteroinferior quadrants and the
      umbo compared to adults with POM. Pathology of the TM and ME occurred in adults
      and children, but severity was greater in children. Residual mesenchyme was
      frequently observed in temporal bones of children. Serious complications such as
      labyrinthtis and meningitis were observed more frequently in children. All cases
      with meningitis had labyrinthitis, previous histories of otitis media and had
      been treated with antibiotics. Although POM occurs in both children and adults,
      pathologic changes of the middle ear are more severe, and complications
      (labyrinthitis and meningitis) occur more often in children. Our findings suggest
      the need to monitor children carefully under the age of 2 years who have POM.

PMID- 11954936
TI  - The diagnostic significance of the 3D-reconstructed MRI in vestibular schwannoma
      surgery: prediction of tumor origin.
AB  - In hearing preservation surgery for the treatment of vestibular schwannoma (VS),
      one of the important factors is the determination of the origin of VS. In this
      study, we investigated the diagnostic significance of using an MRI obtained by
      the three-dimensional Fourier transform fast spin-echo technique (3D
      reconstructed MRI) in order to determine the origin of VS. The subjects consisted
      of 20 patients with mainly intra-canalicular sized VS who underwent tumor removal
      at our hospital. The origin of VS was determined from the 3D-reconstructed MRI
      findings and the results of the caloric test. These findings were then compared
      with the surgical findings. In 15 out of 20 patients, the MRI findings closely
      corresponded to the surgical ones, while the origin of VS hardly could be
      detected when a tumor filled up to the fundus acoustics on the MRI findings of
      the axial sections. On the other hand, 6 out of 15 patients (40%) whose tumor
      originated from the inferior vestibular nerve showed canal paresis. In
      conclusion, 3D-reconstructed MRI is considered to be helpful in obtaining more
      precise information regarding the origin of VS compared to the caloric test.

PMID- 11954937
TI  - Virtual endoscopy imaging of the middle ear cavity and ossicles.
AB  - Ten cadaver temporal bone blocks were studied with high-resolution computed
      tomography (HRCT) in order to produce topographic images, which are more
      informative than ordinary CT slices. Virtual endoscopic images were produced with
      separate, commercially available software, paying attention to the middle ear
      cavity and ossicles. Four major viewing locations for virtual endoscopy (the ear
      canal, hypotympanum, attic and eustachian tube) developed images acceptably. The
      malleus and incus were visualized properly. Small structures such as the
      lenticular process and the stapes sometimes failed to have good imaging. The
      eustachian tube and attic virtual views, which are usually not receptive to
      ordinary endoscopy, gave proper visualization of middle ear structures. Even the
      smallest structure, the stapes, can produce a virtual image.Virtual endoscopic
      images, or topographic images, of the middle ear and ossicles contribute to the
      understanding of the anatomy of the middle ear, thus enhancing the chances for
      successful surgery.

PMID- 11954938
TI  - An indolent course of multiple myeloma mimicking a solitary thyroid cartilage
      plasmacytoma.
AB  - Multiple myeloma, solitary plasmacytoma, and extramedullary plasmacytoma
      constitute a continuum of a disease spectrum, which is called plasma cell
      neoplasms. These three entities can not be differentiated from each other on a
      histological basis and, for this reason, clinical evaluation is important in
      their differential diagnoses. Differential diagnosis guides the proper planning
      of treatment and helps in estimation of survival. Multiple myeloma located within
      the larynx is very rare. Because of its rarity, any established diagnostic and
      treatment criteria do not exist. In this report, a case of laryngeal multiple
      myeloma is presented for its extraordinary presentation and also for educational
      purposes.

PMID- 11954939
TI  - T2 laryngeal carcinoma with impaired mobility: subtypes with therapeutic
      implications.
AB  - The aim of this study was to evaluate the outcome in the treatment of T2
      laryngeal carcinoma with impaired laryngeal mobility, comparing surgical
      management to radiotherapy in terms of local control and survival. The files of
      66 patients treated between 1988 and 1994 were retrospectively studied for tumor
      location, treatment and outcome. Forty-two patients were treated surgically and
      24 by radiotherapy. Follow-up averaged 8.5 years. Local recurrence occurred in
      12.5% of the cases treated by conservation laryngeal surgery and in 21% of the
      cases by radiotherapy. Ultimate laryngeal preservation was achieved in 90.9% of
      the cases initially treated by partial laryngectomy and in 87.5% of the cases
      treated by radiotherapy. Five-year actuarial survival rates were 90% and 28%,
      respectively. A higher rate of metastases and second primaries occurred in the
      group treated by radiotherapy. T2 laryngeal carcinoma amenable to partial
      laryngectomy had a higher local control rate than the cases not amenable to
      conservation surgery and treated by radiotherapy. Tumors differed in the two
      treatment groups in location and extensions, despite the fact that all were T2
      tumors. We emphasize the limits of retrospective studies. Only prospective
      randomized studies will determine the true results of surgery versus radiotherapy
      for a homogeneous subset of T2 laryngeal tumors.

PMID- 11954940
TI  - Number and location of radiolabeled, intraoperatively identified sentinel nodes
      in 48 head and neck cancer patients with clinically staged N0 and N1 neck.
AB  - The value of sentinel node (SN) biopsy for squamous cell carcinoma of the head
      and neck (HNSCC) has not been determined yet. A critical evaluation of this
      concept seems to be mandatory with regard to the increasing acceptance of SN
      biopsy in other tumor entities. Against the background of the results of 48
      previously untreated patients, a reproducible technique for SN biopsy in the head
      and neck level, which has been adjusted to the special topographic conditions of
      this anatomic region, is presented. Methods included intraoperative SN biopsy,
      which was performed in 48 previously untreated patients suffering from squamous
      cell carcinoma (2x lower lip, 8x oral cavity, 20x oropharynx, 15x larynx, 3x
      hypopharynx). Using ultrasound imaging, 43 patients were staged as N0 necks, and
      5 patients were staged as N1 necks. Fine-needle aspiration cytology (FNAC) was
      performed in cases of doubt. Surgery on the neck was carried out according to the
      suspected stage of lymphogenic spread once the SN1 as well as one or two further
      hot nodes (SN2, SN3) had been identified. Numbers and distribution of the
      intraoperatively excised nodes SN1-3 were documented according to their relation
      to the tumor location. Post-operatively, the histologic results of the
      intraoperatively excised nodes SN1-3 were compared to the histologies of the neck
      dissection specimen. Results showed that in all 48 patients, a SN1 could be
      identified intraoperatively. In 20 cases an additional SN2 and in 6 cases a SN3
      was diagnosed. In carcinomas of the lower lip and oral cavity, the SN1 was found
      in 4 cases in level I (2x lower lip, 2x floor of the mouth) and in 6 cases in
      level II (6x lateral tongue). In carcinomas of the oropharynx, the respective
      nodes were found in 17 of 20 cases in level II (carcinomas of the tonsil) and in
      3 cases in level III (carcinomas of the base of the tongue). In supraglottic
      carcinomas the SN1 was identified in 8 of 10 cases in level II and in 2/5
      patients with glottic carcinomas, while in 3/5 glottic carcinomas as well as in
      all hypopharyngeal carcinomas, the SN1 was found in level III. In relation to the
      predictiveness of the detected SN, it has to be remarked that in 38 patients a
      SN1 free of tumor was representative for the regional lymph node status (pN0). An
      isolated metastasis (pN1) was diagnosed in the SN (9x SN1, 1x SN2) in 10
      patients. In conclusion, the results of a SN biopsy modified to a strictly
      intraoperative method of detection are encouraging. Critical indications showed
      that a thorough and standardized technical performance of the injection as well
      as a mandatory, so far unchanged, neck dissection form the basis for the
      development of a SN concept for SCCs of the upper aerodigestive tract. The value
      of the SN concept, however, currently remains unclear for patients suffering from
      HNSCC.

PMID- 11954941
TI  - Correlation between voice handicap index and voice laboratory measurements in
      dysphonic patients.
AB  - Factors underlying voice disorders can be categorized into three distinct
      domains: emotional, physical, and functional. The Voice Handicap Index (VHI)
      subjectively evaluates voice disorders in terms of these three factors. On the
      other hand, Voice Laboratory Measurements (VLM) use objective criteria to
      evaluate the severity of voice disorders. Use of these two different tests (VHI
      and VLM) on dysphonic patients has, however, tended to yield results that vary
      widely in their conclusions. This report reviewed 135 testing sessions on
      dysphonia patients. Seventy-nine of the tests were VHI, and 56 were VLM. All VHI
      and VLM parameters were entered into a statistical program and analyzed using a
      Pearson correlation. The results show that each VHI parameter provides a
      significant level of reliability (P < 0.01) when compared with other VHI
      parameters. Four VLM parameters also demonstrated significant reliability (P <
      0.01) in comparison with other VLM parameters. However, when comparing across
      testing methods, VHI and VLM parameter reliability is shown to be poor (P >
      0.05). With such a large discrepancy between the results of VHI and VLM testing,
      no objective parameter can yet be regarded as a definitive prognostic factor in a
      subjective evaluation of dysphonic patients.

PMID- 11954943
TI  - Nicorandil enhances myocardial tolerance to ischemia without progressive
      collateral recruitment during coronary angioplasty.
AB  - Nicorandil, a hybrid nitrate and ATP-sensitive potassium channel opener, has had
      a preconditioning effect in some coronary angioplasty studies. The present study
      investigated whether the cardioprotective effects of nicorandil involve coronary
      collateral function. Thirty-two patients with stable angina pectoris were
      randomized to receive a 1-min intravenous infusion of nicorandil (100 microg/kg)
      or normal saline. Five minutes later they underwent three 2-min balloon
      inflations 5-min apart. The maximum ST-segment elevation (deltaSTmax), the sum of
      ST-segment elevations in all leads (sigmaST), and the chest pain score were
      determined at the end of each balloon inflation. The collateral flow index (CFI)
      was derived from simultaneous measurement of the mean aortic pressure and the
      coronary wedge pressure obtained from a pressure guidewire during balloon
      inflation. The deltaSTmax, sigmaST, and chest pain score decreased progressively
      during the 3 sequential balloon inflations in both groups, and the deltaSTmax and
      sigmaST were less in the nicorandil group than in the control group during each
      inflation. The CFI did not change during the 3 inflations in either group and was
      similar in the 2 groups during each inflation. In conclusion, pretreatment with
      intravenous nicorandil enhances myocardial tolerance to ischemia without
      progressive collateral recruitment during coronary angioplasty.

PMID- 11954942
TI  - Quinapril prevents restenosis after coronary stenting in patients with
      angiotensin-converting enzyme D allele.
AB  - Restenosis after coronary artery stent implantation is attributed chiefly to
      intimal hyperplasia, which is prevented experimentally by angiotensin-converting
      enzyme (ACE) inhibitors. Therefore, the present study investigated whether the
      effect of quinapril, a tissue-specific ACE inhibitor, on the prevention of
      coronary restenosis differs according to ACE polymorphism. One hundred
      consecutive patients with successful stent implantation were randomly assigned to
      quinapril and control groups. Both follow-up angiography and ACE polymorphism
      analysis were obtained from 92 patients (control, 46; quinapril treatment, 46).
      The prevalence of risk factors did not differ statistically according to
      quinapril treatment or ACE genotypes. There was no statistically significant
      difference in the occurrence of restenosis 6 months after stenting between the
      groups. Quantitative coronary angiography revealed that quinapril treatment
      resulted in significantly higher minimal lumen diameter and significantly lower
      percent diameter stenosis (22.9 +/- 22.6 vs 37.1 +/- 19.7% in the control group,
      p < 0.05) in patients with the D allele although there was no difference in those
      with the II genotype. In addition, intravascular ultrasound revealed that
      quinapril treatment significantly prevented the loss of minimal lumen cross
      sectional area and the increase in percent area stenosis (34.5 +/- 14.0 vs 53.3
      +/- 16.4% in the control group, p < 0.05) in patients with the D allele compared
      to those with the II genotype. These results suggest that the administration of
      ACE inhibitors for the attenuation of lumen loss after coronary stent
      implantation is best for subjects with the D allele of the ACE genotype.

PMID- 11954944
TI  - Epidemiologic and clinical characteristics of cardiomyopathies in Japan: results
      from nationwide surveys.
AB  - Nationwide clinico-epidemiological surveys of cardiomyopathies in Japan were
      carried out. Disorders surveyed included idiopathic dilated cardiomyopathy (DCM),
      hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM),
      arrhythmogenic right ventricular dysplasia (ARVD), mitochondrial disease, Fabry's
      disease of the heart and prolonged Q-T interval syndrome. The total number of
      patients was estimated at 17,700 for DCM, 21,900 for HCM, 300 for RCM, 520 for
      ARVD, 640 for mitochondrial disease, 150 for Fabry's disease of the heart, and
      1,000 for prolonged Q-T interval syndrome. The prevalence of both DCM and HCM was
      higher in men than women: the male-to-female ratios were 2.6 and 2.3 for DCM and
      HCM, respectively. Detailed data on patients with DCM or HCM were collected by a
      follow-up survey. In 1 year more patients with DCM (5.6%) died than with HCM
      (2.8%): congestive heart failure (CHF) and arrhythmias were the leading causes of
      death for DCM and HCM, respectively. Angiotensin converting enzyme inhibitors
      (64.6%) and beta-adrenergic blockers (40.9%) are commonly used to treat the CHF
      complicating DCM and may be associated with the clinical improvement in a
      significant number of DCM patients. Thus, the nationwide surveys of Japanese
      patients have yielded important current epidemiological and clinical information
      on the characteristics of cardiomyopathies in Japan.

PMID- 11954945
TI  - Indications for partial left ventriculectomy in pediatric dilated cardiomyopathy.
AB  - The purpose of this study was to define the role and indications of partial left
      ventriculectomy (PLV) in children with end-stage dilated cardiomyopathy (DCM).
      Clinical data were collected by retrospective chart review of children with DCM
      who were treated from 1997 to 2000. Four patients underwent PLV (PLV group) and 5
      patients were managed without PLV (non-PLV group). In the PLV group, 2 patients
      are well 18 and 35 months postoperatively. One infant survived 6 months and then
      successfully underwent heart transplantation, and the other child died of
      hemoptysis 2 weeks postoperatively. Factors affecting outcome were preoperative
      status, in particular whether surgery was performed urgently or electively. In
      the non-PLV group, 4 patients were well controlled by medical treatment and 1
      infant underwent mitral valve replacement for severe mitral regurgitation. The
      cardiothoracic ratio ranged from 72% to 76% in the PLV group and from 45% to 60%
      in the non-PLV group. The percentage of the expected left ventricular diastolic
      dimension ranged from 184% to 218% in the PLV group and from 109% to 163% in the
      non-PLV group. Ejection fractions in the PLV group were from 10% to 22% and from
      36% to 56% in the non-PLV group. The serum brain natriuretic peptide
      concentration was above 1,200 pg/ml in the PLV group and below 168 pg/ml in the
      non-PLV group. In conclusion, PLV is indicated for selected children with end
      stage DCM, and is most appropriate when medical therapy is not effective and
      heart transplantation is unavailable.

PMID- 11954946
TI  - Perfusable tissue index obtained by positron emission tomography as a marker of
      myocardial viability in patients with ischemic ventricular dysfunction.
AB  - In areas of severe asynergy, the clinically important task is to identify
      functionally recoverable myocardium. Fourteen patients with asynergy were
      investigated by H2(15O) dynamic positron emission tomography imaging before
      revascularization. Regional myocardial blood flow (MBF) was determined and the
      water-perfusable tissue fraction (PTF) for each region of interest and the total
      anatomical tissue fraction (ATF) were estimated. The PTF/ATF was analyzed as the
      water perfusable tissue index (PTI). Asynergy was defined as segments with wall
      motion more than 2SD below than that of a normal population. An increase of
      >0.8SD in anterior wall segments with asynergy and an increase of >0.6 SD in
      inferior wall asynergy were defined as significant improvements of wall motion
      indicative of viable myocardium. Fifteen segments with wall motion abnormalities
      less than -2SD and 10 control segments were identified; 7 segments recovered and
      8 segments did not. MBF was similar in both groups of segments before
      revascularization (0.78 +/- 0.27 vs 0.73 +/- 0.18 ml min-(-1) x g(-1), NS). The
      PTI in the recovered segments was significantly higher than that in the
      unimproved segments (0.734 +/- 0.058 vs 0.592 +/- 0.038, p<0.0001) and was
      similar to that of the control segments. After revascularization, the PTI
      correlated with the SD of wall motion (p<0.05, r=0.58). PTI may be a good
      predictor of contractile recovery after revascularization.

PMID- 11954947
TI  - Factors determining peripheral pulmonary artery stenosis remodeling in children
      after percutaneous transluminal balloon angioplasty.
AB  - The peripheral pulmonary artery stenosis (PPS) that complicates congenital heart
      anomalies can improve after percutaneous transluminal balloon angioplasty (PTA),
      despite an initial poor response, but there is little information concerning the
      factors that determine such remodeling. The present study reviewed the
      hemodynamic and angiographic data before, immediately after, and at late follow
      up after PTA for 17 lesions in 14 patients. Lesions were classified into either
      the (+) group (with pulmonary artery remodeling) or the (-) group (without
      remodeling). Remodeling was defined as an increase of more than 30% in the
      predictive percent of normal (%N) of the peripheral pulmonary artery diameter at
      late follow-up compared with the diameter immediately after PTA. Remodeling
      occurred in 6 of 17 lesions (35%), and the pressure gradient immediately after
      PTA was significantly smaller (<10 mmHg) in the (+) group than in the (-) group.
      Late expansion of the lesion (remodeling) occurs after PTA in some children with
      PPS and an adequate initial reduction in the pressure gradient favors subsequent
      remodeling.

PMID- 11954948
TI  - Early and late clinical outcomes following coronary perforation in patients
      undergoing percutaneous coronary intervention.
AB  - Coronary perforation is a rare but serious complication that occurs during
      percutaneous coronary intervention (PCI). This study examines the frequency of
      coronary perforation during PCI, evaluates the management strategies used to
      treat perforations, and describes the long-term prognosis of patients who have
      developed coronary perforation during PCI. Coronary perforations were found in 69
      (0.93%) of 7,443 consecutive PCI procedures, occurring more often after use of a
      new device (0.86%) than after use of balloon angioplasty (0.41%) (p<0.05).
      Coronary perforation was attributable solely to the coronary guidewire in 27
      (0.36%) cases. Coronary perforations were divided into 2 types: (1) Those with
      epicardial staining without ajet of contrast extravasation (type I, n=51), and
      (2) those with a jet of contrast extravasation (type II, n= 18). Patients with
      type I and type II perforations were managed by observation only (35% and 0%,
      respectively), reversal of anticoagulation (57% and 94%), pericardiocentesis and
      drainage (27% and 61%), and prolonged perfusion balloon angioplasty (16% and
      100%). Two patients with type II perforations required emergency coronary artery
      bypass surgery. There were no in-hospital deaths. Late pseudoaneurysms developed
      in 18 (28.6%) patients during the 13.4 +/- 11.3 months' follow-up period, and
      were more common in patients with type II perforations (72.2% vs 11.1% with type
      I perforations; p<0.001). During the follow-up period, no patient had evidence of
      coronary rupture. The results suggest that coronary perforation is uncommon after
      PCI, and can be managed without cardiac surgery in the majority of cases. Late
      pseudoaneurysms developed in some patients, particularly in patients with type II
      perforations, but there were no late consequences of coronary perforation after
      PCI.

PMID- 11954949
TI  - Effects of endoscopic transthoracic sympathicotomy on hemodynamic and
      neurohumoral responses to exercise in humans.
AB  - Endoscopic transthoracic sympathicotomy (ETS) is a minimal invasive procedure of
      thoracic sympathetic block and has been used successfully in the treatment of
      primary palmar hyperhidrosis. To examine the effect of Th 2-3 ETS on hemodynamic
      responses to submaximal upright treadmill exercise in humans, cardiac output,
      plasma noradrenaline and adrenaline at rest and during the last 40s of stage 2 in
      a modified Bruce protocol were measured before and after ETS in 21 patients with
      primary palmar hyperhidrosis. Heart rate, mean arterial pressure, rate-pressure
      product, and noradrenaline decreased at rest and at submaximal exercise after
      ETS. Cardiac index at rest did not change either before or after ETS, but
      decreased (8.9 +/- 0.6 vs 6.8 +/- 0.4L x min(-1) m-2; p<0.01, mean +/- SEM) at
      submaximal exercise after ETS. Stroke index and systemic vascular resistance were
      similar both at rest and at submaximal exercise before and after ETS. Thus, ETS
      reduces myocardial oxygen demand and plasma noradrenaline levels both at rest and
      during exercise without significantly depressing cardiac function in terms of
      stroke volume.

PMID- 11954950
TI  - Role of plaque proliferation in late lumen loss after directional coronary
      atherectomy.
AB  - Previous reports suggest that vessel remodeling is the most important factor in
      late lumen loss in non-stented lesions, but because results of directional
      coronary atherectomy (DCA) show that increased plaque area (PA) is also
      important, the aim of this study was to redefine the mechanism of late lumen loss
      after DCA. One hundred and twenty lesions that underwent DCA with intravascular
      ultrasound (IVUS) guidance and serial IVUS analysis were studied, and vessel area
      (VA), lumen area (LA), PA (VA-LA) and corrected values (each value divided by the
      value of VA pre procedure to correct the vessel size) were analyzed. During
      follow-up, corrected VA (cVA) decreased by 0.058 +/- 0.191, whereas corrected PA
      (cPA) increased by 0.087 +/- 0.159. Though the %PA (PA/VA) after the procedure
      showed significant negative correlation with the subsequent change in cPA, it did
      not correlate with the subsequent change in cVA. In conclusions, the mechanism of
      late lumen loss after DCA consists of both arterial remodeling and plaque
      proliferation, and the residual %PA after the procedure determines the subsequent
      lumen loss. With a lower %PA, a change in the PA contributes more to late lumen
      loss than do changes in VA. With a high %PA, a change in the VA contributes more
      to late lumen loss.

PMID- 11954951
TI  - Long-term efficacy of empirical chronic amiodarone therapy in patients with
      sustained ventricular tachyarrhythmia and structural heart disease.
AB  - The efficacy of empirical chronic oral amiodarone therapy in 129 patients with
      sustained ventricular tachyarrhythmia (VTNVF) and structural heart disease is
      evaluated. Twenty-nine patients were treated with class I drugs and monitored by
      electrophysiological study (EPS) and Holter electrocardiogram (ECG) (class I).
      The remaining 100 non-responders to the class I drugs were treated with oral
      amiodarone, of whom 70 were tolerant (AMD+) and 30 were intolerant (AMD-).
      Patients were followed up to 36 months. The primary and secondary end-points were
      recurrence of VT/VF and hypothetical death, respectively; whereby, hypothetical
      death was defined as actual death and the event of rapid VT.VF (heart rate
      >240beats/min) in patients with an implantable cardioverter defibrillator. Class
      I and AMD+ patients showed a better prognosis than AMD- patients. The VT/VF event
      free at 36 months in class I (64.8%) and AMD+ (56.1%) patients were significantly
      higher than that in AMD- (27.2%) (p<0.01) patients. Hypothetical survival rates
      in class I (92.0%) and AMD+ (83.6%) patients were significantly higher than that
      in AMD- (57.0%) (p<0.001) patients, but there were no significant differences in
      the actual survival rate among the 3 patient groups. The independent clinical
      factors suppressing the recurrence of VT/VF (Cox hazard) were treatment with
      amiodarone (p=0.02, 95% confidence interval (CI) =0.19-0.86) and EPS/Holter ECG
      guided Class I drugs (p=0.04, 95% CI=0.14-0.94). The results demonstrate that
      empirical amiodarone has a substantial long-term benefit that is comparable to
      EPS/Holter ECG-guided class I drugs in the treatment of high-risk patients with
      VT/VF and structural heart disease.

PMID- 11954952
TI  - Influence of colforsin daropate hydrochloride on internal mammary artery grafts.
AB  - The effect of colforsin daropate hydrochloride (colforsin), a water-soluble
      forskolin derivative, on blood flow in internal mammary artery (IMA) grafts was
      evaluated in a prospective randomized study of 26 patients undergoing coronary
      artery bypass grafting. Patients were randomized to receive either colforsin
      treatment (colforsin; n=14) or no colforsin treatment (control; n=14).
      Administration of colforsin (0.5mg x kg(-1) min(-1)) was started after induction
      of anesthesia and was continued for 6 h. IMA blood flow and hemodynamic
      measurements were assessed perioperatively. During cardiopoulmonary bypass (CPB),
      perfusion flow was adjusted to 2.5 L/m2 and IMA free blood flow was measured. IMA
      blood flow was also measured 1 h after CPB by an ultrasonic flow meter. Systemic
      vascular resistance was significantly lower in the colforsin group during and
      after CPB. IMA blood flow was significantly greater in the colforsin group than
      in the control group during (44 +/- 2 vs 33 +/- 3 ml min-1 x m(-2), p=0.02) and
      after CPB (38 +/- 6 vs 20 +/- 3ml x min(-1) m(-2), p=0.01). IMA blood flow 1 h
      after CPB correlated inversely with concurrent systemic vascular resistance (r=
      0.61, p=0.001). Intraoperative administration of colforsin daropate hydrochloride
      caused potent vasodilation, resulting in an increase in IMA blood flow. The
      results indicate that the regimen can be used perioperatively in patients
      undergoing coronary artery bypass grafting.

PMID- 11954953
TI  - Flecainide augments muscle sympathetic nerve activity in humans.
AB  - The Cardiac Arrhythmia Suppression Trial has shown that treatment with flecainide
      is associated with an increased incidence of cardiac death in patients following
      myocardial infarction. It is believed that there is a complex mechanism involving
      an interaction between flecainide, sympathetic activation, and acute ischemia
      that is responsible for the increased risk of sudden death. The purpose of this
      study was to determine the effects of flecainide on muscle sympathetic nerve
      activity (MSNA) in humans. We measured MSNA using microneurography and cardiac
      output using the dye dilution method in 30 healthy individuals. Measurements were
      made at rest and after the oral administration of flecainide (200mg, n=12) or
      placebo (n=9), or intravenous administration of propranolol (0.2 mg/kg, n=9).
      Flecainide significantly increased heart rate and decreased the cardiac index
      (both p<0.01). Flecainide increased the burst rate from 16.7 +/- 3.5 to 23.3 +/-
      4.1 bursts/min and the burst incidence from 26.6 +/- 5.1 to 34.7 +/ 
      5.6bursts/100 heartbeats (both p<0.01). For all of the hemodynamic parameters
      except heart rate, the effects of propranolol were similar to those of
      flecainide. Propranolol also increased the burst rate by 52 +/- 34% and the burst
      incidence by 106 +/- 39%. These results suggest that flecainide suppresses
      myocardial contractility and produces reflex-mediated increases in sympathetic
      nerve firing in humans.

PMID- 11954954
TI  - Evaluation of arteriolar hyalinosis of the skin of patients with chronic
      congestive heart failure.
AB  - To investigate whether microvascular lesions are present in the skin of patients
      with chronic congestive heart failure (CHF), skin biopsies were performed at the
      time of cardiac catheterization, and the results were compared with control
      subjects. The diagnosis of CHF was done by cardiac catheterization with reference
      to the elevation of plasma levels of brain natriuretic peptide (BNP). Although
      the severity of arteriolar hyalinosis did not correlate with the New York Heart
      Association functional class, increased hyalinosis was found in skin biopsies
      from 17 of 20 patients with CHF, but in none of the 6 control subjects. These
      results indicate that microangiopathic alterations in arterioles may exist in
      patients with CHF and therapy for peripheral vascular remodeling might be
      considered for such patients.

PMID- 11954955
TI  - Suppression of myocardial inflammation using suramin, a growth factor blocker.
AB  - Autoimmune myocardial injuries are involved in the pathogenesis of myocarditis
      and dilated cardiomyopathy, but effective strategies for treating myocardial
      inflammation have not yet been established. The present study investigated the
      effects of suramin, a growth factor blocker, on experimental autoimmune
      myocarditis (EAM) in rats. Lewis rats were immunized with cardiac myosin and
      placed into one of 4 groups: every 72 h for 1 month the control group (C) was
      subcutaneously injected with saline; group L received 4mg/kg of suramin; group M,
      10 mg/kg: group H, 40 mg/kg. The heart weight/body weight ratios of the M and H
      groups were significantly lower than that of the C group. Macroscopic and
      microscopic scores for myocarditis were reduced in the M and H groups. The
      expression of transforming growth factor (TGF)-beta mRNA in the heart was
      significantly decreased in the M and H groups compared with the C. In the next
      experiment, we investigated the effects of suramin on the cytokine milieu in EAM.
      The serum level of interleukin-10 on day 15 was significantly increased by
      suramin treatment. Furthermore, suramin increased the number of T cells with Th2
      function in the popliteal lymph nodes. Suramin suppressed myocardial inflammation
      in EAM and was associated with modulation of the Th1/Th2 cytokine milieu and
      reduced TGF-beta1 expression in the heart.

PMID- 11954956
TI  - Inhibition by KB-r7943 of the reverse mode of the Na+/Ca2+ exchanger reduces Ca2+
      overload in ischemic-reperfused rat hearts.
AB  - Ca2+ influx via the Na+/Ca2+ exchanger (NCX) may lead to Ca2+ overload and
      myocardial injury in ischemia-reperfusion. Direct evidence that increased
      cytoplasmic Ca2+ concentration ([Ca2+]i) is mediated by the reverse mode of the
      NCX is limited, so in the present study the [Ca2+]i dynamics and left ventricular
      pressure were monitored in perfused beating hearts. The effects of KB-R7943
      (KBR), a selective inhibitor of the NCX in the reverse mode, were analyzed during
      low-Na+ exposure and ischemia-reperfusion. Hearts from Sprague-Dawley rats were
      retrogradely perfused and loaded with 4 micromol/L fura-2 to measure the
      fluorescence ratio as an index of [Ca2+]i. To evaluate KBR effects on the reverse
      mode exchanger, the increase in [Ca2+]i induced by low-Na+ exposure (Na+: 30
      mmol/L, 10 mmol/L caffeine pre-treatment) was measured with and without 10
      micromol/L KBR (n=5). In another series, the hearts were subjected to 10 min of
      low-flow ischemia with pacing, followed by reperfusion in the absence (n=6) or in
      the presence of 10 micromol/L KBR (n=6). Background autofluorescence was
      subtracted to estimate the ratio in the ischemia-reperfusion protocol. KBR
      significantly suppressed the increase in [Ca2+]i induced by low-Na+ (40.2 +/-
      11.2% of control condition, p=0.014), as well as on increase in diastolic [Ca2+]i
      during ischemia (% increase from pre-ischemia in [Ca2+]i at 10 min: KBR, 17.9 +/-
      6.4%; no KBR, 44.4 +/- 7.7%; p=0.024). After reperfusion, diastolic [Ca2+]i
      normalized more rapidly in KBR-treated hearts (% increase at 1 min: KBR, 4.5 +/-
      7.0%; no KBR, 39.8 +/- 12.2%; p=0.03). Treatment with KBR also accelerated
      recovery of the rate-pressure product on reperfusion (1 min: KBR, 8,944 +/- 1,554
      min(-1) mmHg; no KBR, 4,970 +/- 1,325; p<0.05). Thus, inhibition of the reverse
      mode exchanger by KBR reduced ischemic Ca2+ overload and possibly improved
      functional myocardial recovery during reperfusion in a whole heart model.

PMID- 11954957
TI  - Rapid increase in cardiac adrenomedullin gene expression caused by acute pressure
      overload: effect of the renin-angiotensin system on gene expression.
AB  - To determine whether acute pressure overload (POL) can stimulate adrenomedullin
      (AM) production, the response of ventricular AM gene expression and plasma AM
      concentration to aortic banding was investigated in the rat. Furthermore, any
      link between AM expression and the renin-angiotensin system (RAS) enhanced by
      acute POL was examined using: a Ca channel blocker (manidipine), an angiotensin
      II type 1 receptor antagonist (candesartan), and an angiotensin-converting enzyme
      inhibitor (quinapril). Rats with acute POL produced by suprarenal aortic banding
      were studied 1, 5 and 14 days after surgery. Plasma AM concentrations in banded
      rats at day 1 increased 1.49-fold (p<0.01), then gradually declined to near the
      control level at day 14. Plasma AM concentrations correlated with plasma renin
      activity (PRA) (p<0.001). Adrenomedullin mRNA expression in the left ventricle
      (LV) increased 1.35-fold (p<0.05) at day 1. This increase was not significant at
      either 5 or 14 days after surgery. Adrenomedullin mRNA expression in the right
      ventricle on days 1 and 5 increased by 1.46-fold (p<0.05) and 1.52-fold (p<0.05),
      respectively. Candesartan, quinapril and manidipine reduced systolic blood
      pressure equally and activated PRA at day 1. However, augmented LV AM gene
      expression was suppressed completely by candesartan and quinapril, but remained
      unaffected by manidipine. In conclusion, POL induces a rapid increase in cardiac
      AM gene expression and in plasma AM concentrations. Cardiac AM transcription
      could therefore be partly regulated by RAS in suprarenal aortic banding rats.

PMID- 11954958
TI  - Cardioprotective effect of mexiletine in acute myocardial ischemia tudies in the
      rabbit closed chest ischemia mode.
AB  - ATP-sensitive K+ (KATP) channel openers have a cardioprotective effect and so
      mexiletine (Mex), a class Ib anti-arrhythmic drug, may also be cardioprotective
      because of its KATP channel-opening effect. The present study examined the effect
      of Mex on acute myocardial ischemia in a closed-chest acute ischemia and
      reperfusion model in rabbits. The rabbits were divided into 3 groups: (1) control
      (n=8); (2) Mex (n=8), continuous infusion of mexiletine (24 mg x kg(-1) h(-1));
      and (3) Mex+Gli (n=8), pre-administration of glibenclamide (Gli; 0.5mg/kg)
      followed by mexiletine infusion. The incidence of arrhythmia, the hemodynamics
      and left ventricular ejection fraction (LVEF), and the infarct size were
      evaluated and compared among the 3 groups. The incidence of fatal ventricular
      fibrillation (VF) was least in the Mex group. The LVEF at 30 min after
      reperfusion was least in the Mex group, but at 360 min after reperfusion, it was
      least in the Mex+Gli group. The area of myocardial infarction determined by 2,3
      triphenyltetrazolium chloride (TTC) staining was smallest in the Mex group. In
      this model, Mex reduced infarct size and improved left ventricular function
      during the late phase after reperfusion, although the effect was totally negated
      by the addition of glibenclamide.

PMID- 11954959
TI  - Effect of ischemic preconditioning and mitochondrial KATP channel openers on
      chronic left ventricular remodeling in the ischemic-reperfused rat heart.
AB  - The influence of ischemic preconditioning (IP) and mitochondrial ATP-sensitive
      potassium (mito-KATP) channel openers on chronic left ventricular (LV) remodeling
      remains unknown, so the effect of IP and mito-KATP channel openers on the LV
      pressure-volume curve was assessed in rats subjected to 30 min ischemia followed
      by a 3-week reperfusion. Infarct size was histologically determined at 3 weeks
      after reperfusion. The LV pressure-volume curve was significantly shifted left by
      IP, diazoxide and nicorandil compared with the controls. These effects were
      blocked by the selective mito-KATP channel blocker 5-hydroxydecanoate. The LV
      remodeling and the infarct size at 3 weeks after reperfusion correlated well,
      indicating that the reduction of LV remodeling in the ischemic-reperfused model
      was strongly influenced by attenuation of the ischemic injury. LV remodeling in
      the chronic phase is attenuated by IP and mito-KATP channel openers with
      concomitant reduction of infarct size.

PMID- 11954960
TI  - Ultrasonic tissue characterization in acute myocarditis: a case report.
AB  - A 25-year-old woman was admitted because of acute myocarditis. Echocardiogram
      revealed hypokinesis of the left ventricle with increased wall thickness, but on
      day 7, the wall motion normalized. Cyclic variation of myocardial integrated
      backscatter on day I was reduced to 1.8 dB (normal range, 2.9-5.3 dB) and
      normalized to 3.2 dB on day 3. The normalization of the cyclic variation of
      integrated backscatter in the myocardium preceded the recovery of the left
      ventricular wall contractility, suggesting the ability of tissue characterization
      to predict recovery of cardiac function.

PMID- 11954961
TI  - Surgical removal of intra-aortic balloon catheter with fractured nitinol central
      lumen: a case report.
AB  - A 73-year-old woman suffering from septic shock was given circulatory assistance
      by intra-aortic balloon pumping (IABP). Eleven hours later, pumping stopped
      abruptly and blood reflux was observed in the intra-aortic balloon catheter
      (IABC). We removed it and inserted another IABC; 3.5 h later, pumping stopped
      again and blood reflux was seen. Removal of the IABC was attempted, as the
      systolic aortic pressure remained above 100 mmHg, but there was resistance during
      the removal and as a result 7.5cm of the catheter from the tip remained inside
      the vessel. Fluoroscopy indicated that the metal tube that formed the central
      lumen in the balloon was fractured, and that its edge had perforated the femoral
      artery. The balloon was then removed surgically. Fracture of the metal tube and
      balloon perforation were confirmed in both the damaged IABCs. Postoperative
      computed tomography and magnetic resonance imaging indicated a highly severe
      posterior-anterior bend in the patient's aorta. A vessel model similar to the
      aorta in this case was made and a reproducibility test was conducted; the central
      lumen fractured within 3 h and under a microscope the profile of the fractured
      test lumen was similar to the one in the clinical case. These findings suggest
      that placing a pumping IABC in a bending aorta causes fracture of the central
      lumen from fatigue failure because the central lumen is under excessive stress.

PMID- 11954962
TI  - Perforation of the descending aorta by the tip of an intra-aortic balloon pump
      catheter.
AB  - Perforation of the proximal descending aorta occurred in a patient on intra
      aortic balloon pump (IABP) support after emergency coronary intervention for
      acute myocardial infarction. The IABP catheter was inserted under fluoroscopic
      guidance into the right femoral artery without difficulty, but after 8 h on IABP
      support the patient went into shock with a left hemothorax. Emergency surgery was
      performed with cardiopulmonary bypass and a perforation of the proximal
      descending aorta with active bleeding was found and successfully repaired. A
      distorted descending aorta in which the IABP catheter was kinked, as in the
      aortic arch, was discovered during surgery and confirmed postoperatively with 3
      dimensional computed tomography scans, particularly in the lateral view. Not only
      the antero-posterior but also the lateral fluoroscopic view is recommended to
      prevent aortic perforation by a kinked IABP catheter.

PMID- 11954963
TI  - Thrombus on the tricuspid valve in a patient with primary antiphospholipid
      syndrome after implantation of an inferior vena cave filter.
AB  - A 62-year-old woman with a history of pulmonary embolism and primary
      antiphospholipid syndrome (PAPS) with positivity for lupus anticoagulant was
      admitted to hospital with shortness of breath. A filter had been implanted in her
      inferior vena cava (IVC) 5 years previously. Emergency echocardiography revealed
      a lobulated, mobile echogenic mass on the tricuspid valve, and on pulmonary
      perfusion scintigraphy several apparently new defects were noted. Fibrinolytic
      therapy improved her symptoms and the pulmonary perfusion, then intravenous
      heparinization was continued for a further week. Repeat echocardiography
      performed on the 7th day of the admission showed complete disappearance of the
      mass, which was retrospectively diagnosed as a thrombus based on its resolution
      with fibrinolytic and anticoagulant therapies.

PMID- 11954964
TI  - Definition of angina in remote follow-up.

PMID- 11954965
TI  - Critical thinking and environmental health: challenging the status quo.

PMID- 11954966
TI  - Thinking processes used by nurses in clinical decision making.
AB  - Clinical decision making forms the basis of expert clinical practice. The purpose
      of this study was to investigate and document the thinking processes used by
      nurses in clinical decision making situations so the processes could guide
      educational practice. Clinical data was analyzed to reveal that clinical decision
      making is complex and requires a variety of thinking processes. Medical and
      surgical nurses used different thinking processes, showing the importance of
      context in clinical decision making. The nursing exemplars and working vocabulary
      developed in this study to describe the thinking processes used in clinical
      decision making can be used in nursing education.

PMID- 11954967
TI  - Preceptorship and critical thinking in nursing education.
AB  - Although preceptorship is being used increasingly by nursing faculty in the
      practice setting, little is known about how preceptors teach and even less is
      known about how critical thinking is being fostered in that relationship. The
      purpose of this study was to examine the process used in preceptorship to develop
      and promote the critical thinking ability of baccalaureate nursing students.
      Using the grounded theory method, this study was conducted in a large tertiary
      care hospital. Participants included fourth-year baccalaureate nursing students
      (preceptees) and their staff nurse preceptors. Data collection was composed of
      semistructured interviews and observations of the preceptors and preceptees as
      they worked together in the practice setting. Secondary data sources included
      documents considered appropriate to the study (e.g., nurse notes, student
      journals). By constant comparative analysis of the data, the findings of this
      study revealed a process that reflects the enabling of students by preceptors to
      develop and promote their critical thinking ability in the practice setting.

PMID- 11954968
TI  - Nursing students' experiences with and strategic approaches to case-based
      instruction: a replication and comparison study between two disciplines.
AB  - In the classroom and in clinical areas, knowing how to learn, reason, reflect,
      think creatively, generate and evaluate ideas, make decisions, and solve problems
      have been identified as key elements of critical thinking. However, to be
      successful in the current health care arena, caregivers cannot be satisfied with
      possessing the ability to solve problems and simply meet preestablished
      "outcomes" (Alfaro-LeFevre, 1998). It is necessary to improve knowledge and
      practice applications and to explore the best ways to do things within a work
      group. This qualitative study evaluated the experiences of senior-level nursing
      students using case-based instruction in a course titled, Leading and Managing in
      Nursing. It is a replication and extension (Phase II) of an original case-based
      instruction study, completed with senior physical therapy students (Phase I).
      Phase III of this study trajectory is the creation of an interdisciplinary case
      based course that addresses either or both clinical collaborative care issues or
      leadership and management issues for health care profession students. From this
      Phase II study, six thematic groupings emerged as distinct student experiences in
      case-based instruction-motivation, real world, learning, knowledge development,
      emerging from within, and group dynamic issues.

PMID- 11954969
TI  - Evaluation of a process-focused learning strategy to promote critical thinking.

PMID- 11954970
TI  - Senior nursing students' participation in a community research project: effect on
      student self-efficacy and knowledge concerning drug interactions arising from
      self-medication in older adults.

PMID- 11954971
TI  - Using structured clinical preparation to stimulate reflection and foster critical
      thinking.

PMID- 11954972
TI  - Stimulating enthusiasm for research in undergraduate nursing students.

PMID- 11954980
TI  - Psychometric properties of the French version of the Karasek Job Content
      Questionnaire: a study of the scales of decision latitude, psychological demands,
      social support, and physical demands in the GAZEL cohort.
AB  - OBJECTIVES: The objective of this study was to explore the psychometric
      properties of the French version of the Karasek Job Content Questionnaire (JCQ)
      for the recommended scales of psychological demands, decision latitude, social
      support, and physical demands. Internal consistency, factorial validity, and
      convergent validity were examined in a large occupational cohort of men and
      women. METHODS: This study was based on the GAZEL cohort composed of workers aged
      40-50 years for men and 35-50 years for women employed by the French national
      electric and gas company Electricite De France-Gaz De France (EDF-GDF) in 1989.
      This cohort has been followed up since 1989 by means of yearly self-administered
      questionnaires and by the collection of data provided by the company. RESULTS:
      The study population included the 11,447 GAZEL subjects, 8,277 men and 3,170
      women, who were working and who answered the French version of the JCQ in 1997.
      Cronbach's alpha coefficients higher than 0.65 supported the internal consistency
      of the JCQ scales and subscales. The results of exploratory factor analysis were
      consistent with the expected dimensions. Physical demands, supervisor support,
      and co-worker support were clearly found. However, for decision latitude,
      'repetitive work' and 'learn new things' displayed low factor loadings. For
      psychological demands, low factor loadings were observed for 'conflicting
      demands', 'wait on others', and 'no excessive work'. Confirmatory factor analysis
      supported the instrument construct in six latent factors: psychological demands,
      skill discretion, decision authority, supervisor support, co-worker support, and
      physical demands, although the items mentioned earlier displayed low standardized
      factor loadings. The associations between the JCQ scales and gender, age,
      educational level, occupational grade, and job satisfaction were explored using
      analysis of variance and chi-square test, and supported the convergent validity.
      CONCLUSION: Although our results of factor analysis could invite the revision of
      the two scales of decision latitude and psychological demands, this study
      provided evidence of the validity of the French version of the four JCQ scales of
      psychological demands, decision latitude, social support, and physical demands
      among a large population consisting of French working men and women.

PMID- 11954981
TI  - The psychometric properties of Karasek's demand and control scales within a
      single sector: data from a large teaching hospital.
AB  - OBJECTIVE: This paper reviews the psychometric properties of the core components
      from Karasek's job content questionnaire, the decision latitude and psychological
      job demands scales. METHODS: A self-reported survey was administered in 1995
      (time 1), 1996 (time 2), and 1997 (time 3) to employees of a large teaching
      hospital. Analyses for this paper are based on data from the 484 employees who
      responded at times 1 and 2. RESULTS: Both scales demonstrated acceptable internal
      consistency as assessed by item-total correlations and Cronbach's alpha. In
      confirmatory factor analysis, the two-factor decision latitude model adequately
      fit the data. However, our findings suggest that a two-factor model may provide
      an improved fit over the original one-factor demands model, suggesting that this
      scale may be two distinct subscales. Lastly, the scales demonstrated acceptable
      discriminant validity. CONCLUSION: Apart from some guarded uncertainty over what
      the demands scale may be measuring, overall, the two scales appeared to perform
      reasonably well in this sample of health care workers.

PMID- 11954983
TI  - Heat waves in Madrid 1986-1997: effects on the health of the elderly.
AB  - OBJECTIVE: The objective of this paper is to analyse and quantify the effects
      exerted on summer mortality by extremes of heat, particularly among persons aged
      65-74 and 75 years and over, groups in which mortality is higher. METHODS: The
      study included the period from 1 January 1986 to 31 December 1997, for all people
      aged over 65 years resident in Madrid, based on mortality due to all causes
      except accidents (ICD-9 codes 1-799), and circulatory (390-459) and respiratory
      (460-487) causes. Meteorological variables analysed were: daily maximum
      temperature, daily minimum temperature and relative humidity. To control the
      effect of air pollution on mortality we considered the daily mean values of
      sulphur dioxide (SO2), total suspended particulate (TSP), nitric oxides (NOx),
      nitrogen dioxide (NO2) and tropospheric ozone (O3). Univariate and multivariate
      ARIMA models were used. Box-Jenkins pre-whitening was performed. RESULTS: The
      results yielded by this study indicate a mortality increase up to 28.4% for every
      degree the temperature rises above 36.5 degrees C, with particular effect in
      women over the age of 75 years and circulatory-cause mortality. The first heat
      wave that leads to the greatest effects on mortality, due to the higher number of
      susceptible people and the duration of the heat wave, show an exponential growth
      in mortality. Furthermore, low relative humidity enhances the effects of high
      temperature, linking dryness to air pollutants, ozone in particular. CONCLUSIONS:
      Since a warmer climate is predicted in the future, the incidence of heat wave
      should increase, and more comprehensive measures, both medical and social, should
      be adopted to prevent the effects of extreme heat on the population, particularly
      the elderly.

PMID- 11954982
TI  - Assessment of the risk of heat disorders encountered during work in hot
      conditions.
AB  - OBJECTIVE: To co-ordinate the work of the main European research teams in the
      field of thermal factors in order to develop and improve significantly the
      methods presently available for assessing the risks of heat disorders encountered
      during work in hot conditions. METHOD: Each item from the required sweat rate
      model was reviewed on the basis of the most recent literature. A database with
      1,113 laboratory and field experiments, covering the whole range of hot working
      conditions, was assembled and used for the validation. RESULTS: Influence of
      clothing ensemble on heat exchange: methods and formulas were developed that take
      into account the dynamic effects associated with forced convection and the
      pumping effect associated with body movements and exercise. Prediction of the
      average skin temperature: the model used in the required sweat rate standard ISO
      7933 was extended to cover more severe conditions with high radiation and high
      humidity and different clothing and take into account the rectal temperature for
      the prediction of the skin temperature. Criteria for estimating acceptable
      exposure times in hot work environments: criteria were reviewed and updated
      concerning the maximum increase in core temperature and the acceptable water
      loss, for acclimatised and nonacclimatised subjects. These limits are intended to
      protect 95% of the population. Measuring strategy: a strategy was developed to
      assess the risks in any working situation with varying conditions of climate,
      metabolic rate or clothing. A detailed methodology was developed in three stages:
      an "observation" method for the recognition of the conditions that might lead to
      thermal stress; an "analysis" method for evaluating the problem and optimising
      the solutions; and an "expert" method for in-depth analysis of the working
      situation when needed. VALIDATION: the different results were used to prepare a
      revision of the interpretation procedure proposed in the ISO standard 7933. We
      validated the modified approaches using the database. This involved the whole
      range of conditions for which the model was extended, namely conditions with high
      and low radiation, humidity and air velocity as well as fluctuating conditions.
      Based on these results, the predicted heat strain model was developed: it is
      presently proposed as an ISO and CEN standard.

PMID- 11954984
TI  - Experiments on effects of an intermittent 16.7-Hz magnetic field on salivary
      melatonin concentrations, rectal temperature, and heart rate in humans.
AB  - OBJECTIVES: The present experiments concerned the hypothesis that an
      intermittent, strong and extremely low frequency magnetic field reduces salivary
      melatonin levels and delays consecutively the nadirs of rectal temperature and
      heart rate. METHODS: Twelve healthy young men (18-25 years) participated in three
      randomly permuted sessions, which were performed as constant routines. The
      participants kept a strict bed rest over 26 h, air temperature was 20 degrees C,
      illumination < 30 lx, and sound level < 50 dBA. Salivary melatonin levels were
      determined hourly, rectal temperature and heart rate were registered continuously
      throughout. An intermittent magnetic field was administered in one session from 6
      p.m. to 2 a.m. at 16.7 Hz, 0.2 mT and alternating on/off-periods of 15 s. This
      situation was compared with a control session without any additional stress.
      Another session was performed to determine the participants' ability to respond
      to a well-known melatonin-suppressing stress, namely bright light (1,500 lx, 10
      p.m.-2 a.m.). RESULTS: Bright light inhibited melatonin synthesis in all 12
      participants and delayed the nadirs of rectal temperature and heart rate. The
      only significant alteration that was associated with exposure to the magnetic
      field was a delay in the heart rate nadir, which was not mediated by an
      accordingly altered melatonin profile. CONCLUSION: The fact that the circadian
      rhythm of only the heart rate was altered indicates an internal dissociation
      which might constitute a health risk in the long run and needs to be investigated
      more extensively.

PMID- 11954985
TI  - The relationship between hand-arm vibration and lower extremity clinical
      manifestations: a review of the literature.
AB  - OBJECTIVE: To assess the current literature supporting a relationship between
      hand-arm vibration (HAV) and lower extremity clinical effects. METHODS: An
      initial review of the literature identified lower extremity vascular and
      neurological effects reported in association with HAV. A second literature review
      was performed with explicit search and evaluation strategies. It focused on
      analytical studies and looked for epidemiological evidence supporting the
      relationship between HAV and lower extremity effects. RESULTS: Eight analytical
      studies which met all of the initial inclusion/exclusion criteria were
      identified. All of these had serious validity deficiencies with respect to
      selection bias, response rates and lack of examination of confounders.
      CONCLUSIONS: There was consistency with respect to an association between those
      exposed who were diagnosed with hand-arm vibration syndrome (HAVS) and vascular
      symptoms in the lower extremities. There was no evidence that hand-held vibration
      exposure independent of the diagnosis of HAVS was associated with lower extremity
      vascular symptoms. There was no evidence to suggest that HAV was associated with
      clinically significant lower extremity neurological symptoms.

PMID- 11954986
TI  - Effects of chromic acid exposure on immunological parameters among electroplating
      workers.
AB  - OBJECTIVE: To investigate the immunological parameters of chromic acid exposure
      among electroplating workers. METHODS: Forty-six subjects were selected from five
      electroplating plants in central Taiwan. Each subject was interviewed by
      questionnaire, and urine chromium (urine-Cr) concentration was assessed.
      Immunological parameters were evaluated by interleukin (IL-2, IL-4, IL-6, IL-8,
      IL-10, TNF-alpha, IFN-gamma) and levels of lymphocyte subsets (T-cell, B-cell,
      T4, T8 and T4/T8). RESULTS: Levels of IL-6 and IL-8 significantly increased in
      subjects with high urine Cr concentration, but TNF-alpha levels decreased. IL-2,
      IL-4, IL-10 and IFN-gamma were undetected. Flow cytometry was used to determine
      levels of lymphocyte subsets: only B-cells percentage had a negative correlation
      with urine-Cr. Smoking was an important factor that influenced levels of
      lymphocyte subsets. CONCLUSION: Exposure to Cr has a detrimental effect on the
      immune system, so it is evident that worker exposure to chromic acid in the
      electroplating workplace must be reduced to a minimum.

PMID- 11954987
TI  - Isolation and characterization of Bacillus cereus-like bacteria from faecal
      samples from greenhouse workers who are using Bacillus thuringiensis-based
      insecticides.
AB  - OBJECTIVES: Since the discovery of the insecticidal activity of Bacillus
      thuringiensis at the beginning of the twentieth century, this bacterium has been
      used increasingly against various insect pests. In spite of the extensive use of
      B. thuringiensis, only sporadic clinical case reports have been published. In
      recent years, the close relationship between B. thuringiensis and the human
      pathogen Bacillus cereus has been confirmed. In practice, only the insecticidal
      activity of B. thuringiensis distinguishes the two species. However, both species
      are composed of thousands of isolates with varying potential for causing adverse
      effects in humans. The aim of this study was to employ molecular biology methods
      for assessment of occupational exposure to B. thuringiensis-based biopesticides
      by determination of specific genetic information including plasmid profiles and
      random amplified polymorphic DNA (RAPD). METHODS: Faecal samples from 12 persons,
      working in Danish greenhouses, were collected for microbial analysis. Seven
      persons were using B. thuringiensis-based insecticides, whereas five persons were
      employed at greenhouses that did not use B. thuringiensis. The bacteria were
      isolated on B. cereus-specific solid substrate, and colonies were further
      identified using the polymerase chain reaction (PCR). The PCR method was used for
      the identification of the enterotoxin genes HblA and BceT. The expression of
      enterotoxins was detected with two commercial serological kits. Primers specific
      for 16S-23S spacer region were used to identify the bacteria as members of the B.
      cereus group. Several primers towards insecticidal genes have been used in order
      to further characterize the isolates as subspecies of B. thuringiensis. RESULTS:
      Two faecal samples from the B. thuringiensis-exposed greenhouse workers were
      positive for B. cereus-like bacteria. One isolate displayed intracellular
      crystalline inclusions characteristic of B. thuringiensis, production of and
      genes for B. cereus enterotoxins and it was PCR-positive for an insecticidal
      toxin primer set. RAPD profiles of the faecal isolate were identical to that of
      strains isolated from a commercial product. CONCLUSIONS: The methods applied have
      verified that the faecal isolate was identical to the B. thuringiensis isolate
      found in the biopesticide used. This is the first reported case of isolation of a
      bacterial biopesticide from human faeces. The biopesticide was shown to harbour
      and express enterotoxin genes. However, there is no evidence that this caused any
      adverse effects to the person from whom these bacteria were isolated.

PMID- 11954988
TI  - Effects of an external exposure to 200 ppm methyl ethyl ketone on nasal mucosa in
      healthy volunteers.
AB  - OBJECTIVES: To investigate the effects of an acute exposure to 200 ppm methyl
      ethyl ketone on the nasal mucosa of healthy volunteers. METHODS: Nineteen healthy
      non-smoking men were exposed to 200 ppm methyl ethyl ketone and to a sham
      exposure in an exposure chamber, using a cross-over design. Mucociliary transport
      time was determined with the saccharine test. Interleukin (IL)-1beta, IL-6, IL-8,
      and tumor necrosis factor-alpha (TNFalpha) were measured in nasal secretions.
      Subjective symptoms were assessed by questionnaire. RESULTS: Mucociliary
      transport time was significantly higher (660 vs. 600 s (medians), P = 0.01) after
      solvent exposure. Concentrations of IL-1beta and IL-8 were insignificantly
      elevated after exposure (IL-1beta: 83.8 pg/ml vs. 48.1 pg/ml, medians, P = 0.11;
      IL-8: 14471 pg/ml vs. 11080 pg/ml, P = 0.12), whereas those of IL-6 and TNFalpha
      remained unchanged. Subjects did not feel any irritation of nasal mucosa.
      CONCLUSION: Concentrations of organic solvents not exceeding their MAK values can
      cause subclinical rhinitis. The secretion of proinflammatory cytokines and
      impairment of mucociliary transport can explain the development of clinical
      rhinitis in highly exposed subjects.

PMID- 11954990
TI  - Physical beauty: only skin deep?
AB  - Personal appearance and physical beauty are becoming increasingly important in
      our societies and, as a consequence, enter into the realm of medicine and health
      care. Adequate and just health care policies call for an understanding of this
      trend. The core question to be addressed concerns the very idea of beauty. In the
      following, a conceptual clarification is given in terms of beauty's meaning,
      value and function (i.e. beauty that is used instrumentally, and beauty that is
      attained). Furthermore, some relevant distinctions are drawn between physical and
      artistic beauty, and physical beauty in a human sense. The core idea for this is
      formed by a Kantian notion of the beauty concept. It is argued that beauty
      judgements should be understood as relative to persons and their contexts.
      Physical beauty should be taken seriously when it is understood in this deeper
      sense of being related to the shaping of a person's identity.

PMID- 11954989
TI  - Miracles and the limits of medical knowledge.
AB  - In considering whether medical miracles occur, the limits of epistemology bring
      us to confront our metaphysical worldview of medicine and nature in general. This
      raises epistemological questions of a higher order. David Hume's understanding of
      miracles as violations of the laws of nature assumes that nature is completely
      regular, whereas doctrines such as C. S. Peirce's "tychism" hold that there is an
      element of absolute chance in the workings of the universe. Process philosophy
      gives yet another view of the working of nature. Physicians have no
      epistemological grounds for declaring any cure to be miraculous. Miracles are
      theological (or philosophical) entities, and not medical entities. All physicians
      can do is to determine whether or not a cure is scientifically inexplicable
      according to the current epistemological standards of medical science. As these
      standards change, what is currently unexplainable may become explainable.
      However, we can also come to realize that our current explanations are in fact
      unsatisfactory. Our justifications of knowledge claims about miracles will depend
      on our views about determinism and indeterminism. If the universe is not a
      deterministic one, we should be open to the possibility of encountering what
      appear to us as sui generis events. These would not be violations of immutable
      laws of nature, but manifestations of the true workings of nature, and certainly
      causes for wonder.

PMID- 11954991
TI  - Animal experimentation: pro and con arguments using the theory of evolution.
AB  - The theory of evolution has been used in arguments regarding animal
      experimentation. Two such arguments are analyzed, one against and one in favor.
      Each argument stresses the relevance of the theory of evolution to normative
      ethics but attempts explicitly to avoid the so-called naturalistic fallacy.
      According to the argument against animal experimentation, the theory of evolution
      'undermines' the idea of a special human dignity and supports 'moral
      individualism'. The latter view implies that if it is wrong to use humans in
      experiments, then it is also wrong to use animals, unless there are relevant
      differences between them that justify a difference in treatment. No such
      differences can be found with regard to animals which lead 'biographical lives'.
      The argument in favor of animal experimentation is based on evolutionary
      psychology. It states that humans, as all social animals, are speciesist by
      nature and stresses that this should be taken seriously in normative ethics. This
      does not mean that animal interests should not be considered, only that vital
      human interests may outweigh them. In order to assess the arguments, one has to
      take a stand on certain more basic issues: 'is' versus 'ought', impartiality
      versus special obligations, and feelings/intuitions versus reason. Given the
      author's own position with regard to these more basic considerations, the
      evolutionary argument in favor of animal experimentation is judged to be more
      convincing than the one against but not decisive. It is also maintained that not
      all animal experiments are acceptable. Which animal experiments are acceptable
      and which are not has to be decided on a case-by-case basis.

PMID- 11954992
TI  - Imaginative ethics--bringing ethical praxis into sharper relief.
AB  - The empirical basis for this article is three years of experience with ethical
      rounds at Uppsala University Hospital. Three standard approaches of ethical
      reasoning are examined as potential explanations of what actually occurs during
      the ethical rounds. For reasons given, these are not found to be satisfying
      explanations. An approach called "imaginative ethics", is suggested as a more
      satisfactory account of this kind of ethical reasoning. The participants in the
      ethical rounds seem to draw on a kind of moral competence based on personal life
      experience and professional competence and experience. By listening to other
      perspectives and other experiences related to one particular patient story, the
      participants imagine alternative horizons of moral experience and explore a
      multitude of values related to clinical practice that might be at stake. In his
      systematic treatment of aesthetics in the Critique of Judgement, Kant made use of
      an operation of thought that, if applied to ethics, will enable us to be more
      sensitive to the particulars of each moral situation. Based on this reading of
      Kant, an account of imaginative ethics is developed in order to bring the ethical
      praxis of doctors and nurses into sharper relief. The Hebraic and the Hellenic
      traditions of imagination are used in order to illuminate some of the experiences
      of ethical rounds. In conclusion, it is argued that imaginative ethics and
      principle-based ethics should be seen as complementary in order to endow a moral
      discourse with ethical authority. Kantian ethics will do the job if it is
      remembered that Kant suggested only a modest, negative role of principle-based
      deliberation.

PMID- 11954993
TI  - The importance of genetic services for the theory of health: a basis for an
      integrating view of health.
AB  - The first part of this article shows that our effective means to know and modify
      directly the human genetic make-up generates singular and difficult situations
      for the application of fundamental medical categories. Specifically, we
      demonstrate that in dealing with these situations, some predominant views on
      health, such as descriptivism or that which reduces the state of health to not
      having present disabilities, cannot provide adequate answers either from the
      point of view of medical science or in terms of our ordinary intuitions. The
      second part of the article examines the reasons for the failure of these views to
      tackle the mentioned situations, proposes solutions to urgent problems and,
      finally, offers some foundations for an alternative theoretical development, id
      est, for a theory of health able to satisfactorily integrate our genetic
      dimension.

PMID- 11954994
TI  - The role of non-directiveness in genetic counseling.
AB  - When the complete human genome has been sequenced, everyone of us will become a
      potential candidate for genetic counseling and testing. Within a short period of
      time everyone will obtain his personal genetic passport identifying deleterious
      and susceptibility genes. With the availability of presymptomatic tests for late
      onset disorders and the possibilities of prevention and treatment, the conflict
      between directiveness and nondirectiveness will dominate the counseling setting.
      Despite general consent on providing genetic information in a nondirective
      fashion to preserve value neutrality and enhance client's autonomy, there is no
      accepted common definition of what non-directiveness really is or ought to be.
      The article tries to elaborate some aspects which might be fruitful and
      clarifying in the complex issues involved in the black box of genetic counseling.

PMID- 11954995
TI  - Autonomy and freedom of choice in prenatal genetic diagnosis.
AB  - An increase in autonomy and freedom is often considered one of the main arguments
      in favour of a broad use of genetic testing. Starting from Gerald Dworkin's
      reflections on autonomy and choice this article examines some of the implications
      which accompany the increase in choices offered by prenatal genetic diagnosis.
      Although personal autonomy and individual choice are important aspects in the
      legitimation of prenatal genetic diagnosis, it seems clear that an increase in
      choice offered by prenatal genetic diagnosis also leads to various implications
      that may negatively influence the freedom of the persons involved.

PMID- 11954996
TI  - Genetics' dreams in the post genomics era.
AB  - In this paper I explore the heuristic limits of human genetics, in particular the
      claim that it is possible to manipulate human germ cells in a pre-ordinate way
      (Gordon, 1999). I argue that this claim is unrealistic based on genetic
      reductionism and a wrong concept of genetic diseases.

PMID- 11954997
TI  - Ethical guidance on human embryonic and fetal tissue transplantation: a European
      overview.
AB  - This article presents an overview of regulations, guidelines and societal debates
      in eight member states of the EC about a) embryonic and fetal tissue
      transplantation (EFTT), and b) the use of human embryonic stem cells (hES cells)
      for research into cell therapy, including 'therapeutic' cloning. There appears to
      be a broad acceptance of EFTT in these countries. In most countries guidance has
      been developed. There is a 'strong' consensus about some of the central
      conditions for 'good clinical practice' regarding EFTT. International differences
      concern, amongst others, some of the informed consent issues involved, and the
      questions whether an intermediary organisation is necessary, whether the methods
      of abortion may be influenced by the possible use of EFT, and whether EFTT should
      only be used for the experimental treatment of rare disorders. The potential use
      of hES cells for research into cell therapy has given a new impetus to the debate
      about (human) embryo research. The therapeutic prospects with regard to the
      retrieval and research use of hES cells appear to function as a catalyst for the
      introduction of less restrictive regulations concerning research with spare
      embryos, at least in some European countries. It remains to be seen whether the
      prospect of treating patients suffering from serious disorders with transplants
      produced by therapeutic cloning will decrease the societal and moral resistance
      to allowing the generation of embryos for 'instrumental' use.

PMID- 11954999
TI  - Symmetry of O-H-O and N-H-N hydrogen bonds in 6-hydroxy-2-formylfulvene and 6
      aminofulvene-2-aldimines.
AB  - The symmetry of the hydrogen bonds in 6-hydroxy-2-formylfulvene and two N,N'
      diaryl-6-aminofulvene-2-aldimines is probed by the NMR technique of isotopic
      perturbation. Observed deuterium-induced 13C NMR isotope shifts at several
      positions can be attributed to a combination of an intrinsic shift and the
      perturbation of a tautomeric equilibrium. The most dramatic are at the aldehydic
      or aldiminic carbon signals, where the observed isotope shift for the unlabeled
      carbon is +376 or +223 ppb. This large downfield shift is contrary to the small
      upfield shift expected for a four-bond intrinsic shift and can be attributed only
      to a perturbation shift. Therefore these intramolecular hydrogen bonds are
      asymmetric, the proton resides in a double-minimum potential surface, and each
      molecule exists as a pair of rapidly interconverting tautomers, regardless of
      solvent. The symmetry of the hydrogen bond is not governed only by the O-O or N-N
      distance. It is proposed that symmetric hydrogen bonds can be observed in
      crystalline phases but not as yet in solution because the disorder of the
      solvation environment induces an asymmetry of the hydrogen bond, whereas a
      crystal can guarantee a symmetric environment. These results provide no insight
      into the source of the stabilization attributed to low-barrier hydrogen bonds if
      they lack the special feature of symmetry.

PMID- 11955001
TI  - Uncatalyzed and amine catalyzed decarboxylation of acetoacetic acid: an
      examination in terms of No Barrier Theory.
AB  - Rate constants for decarboxylation of acetoacetic acid, its anion, and its imine
      with aminoacetonitrile have been calculated from equilibrium constants and
      distortion energies using No Barrier Theory. The mechanisms of decarboxylation of
      both acetoacetic acid and its imine involve preequilibrium formation of the
      zwitterion.

PMID- 11955000
TI  - A new nonhydrolyzable reactive cAMP analog, (Sp)-adenosine-3',5'-cyclic-S-(4
      bromo-2,3-dioxobutyl)monophosphorothioate irreversibly inactivates human platelet
      cGMP-inhibited cAMP phosphodiesterase.
AB  - Levels of cAMP that control critical platelet functions are regulated by cGMP
      inhibited cAMP phosphodiesterase (PDE3A). We previously showed that millimolar
      concentrations of the hydrolyzable 8-[(4-bromo-2,3-dioxobutyl)thioadenosine 3',5'
      cyclic monophosphate (8-BDB-TcAMP) inactivate PDE3A. We have now synthesized a
      nonhydrolyzable affinity label to probe the active site of PDE3A. The
      nonhydrolyzable adenosine 3',5'-cyclic monophosphorothioates, Sp-cAMPS and Rp
      cAMPS, function as competitive inhibitors of PDE3A with K(i) = 47.6 and 4400
      microM, respectively. We therefore coupled Sp-cAMPS with 1,4-dibromobutanedione
      to yield (Sp)-adenosine-3',5'-cyclic-S-(4-bromo-2,3
      dioxobutyl)monophosphorothioate, [Sp-cAMPS-(BDB)]. Sp-cAMPS-(BDB) inactivates
      PDE3A in a time-dependent, irreversible reaction with k(max) = 0.0116 min(-1) and
      K(I) = 10.1 microM. The order of effectiveness of protectants in decreasing the
      rate of inactivation (with K(d) in microM) is: Sp-cAMPS (24) > Rp-cGMPS (1360),
      Sp-cGMPS (1460) > GMP (4250), AMP (10600), Rp-cAMPS (22170). These results
      suggest that the inactivation of PDE3A by Sp-cAMPS-(BDB) is a consequence of
      reaction at the overlap of the cAMP and cGMP binding regions in the active site.

PMID- 11955002
TI  - Facile hydrogen-deuterium exchange at the 5'-position of an analogue of S
      adenosyl-l-methionine.
AB  - S-3',4'-anhydroadenosyl-l-methionine is an analogue of the S-adenosyl-l
      methionine coenzyme. Here we report on a rapid solvent exchange of the methylene
      protons at the 5'-position of this analogue. The rate of H/D exchange was
      measured by nuclear magnetic resonance spectroscopy under buffered conditions in
      deuterium oxide. The reaction is specific base catalyzed and displays a second
      order rate constant of 2 x 10(4) M(-1) s(-1), which corresponds to a rate
      enhancement of 10(12) compared to solvent exchange of alpha-methylene protons in
      acyclic, aliphatic sulfonium ions. No other carbon bonded hydrogens in the
      molecule exchange with solvent under the experimental conditions. Allylic
      stabilization of a carbanionic-like transition state for the solvent exchange
      process can account for these results. Solvent exchange under these mild
      conditions provides a simple way to prepare a 5'-2H-labeled form of the coenzyme
      analogue.

PMID- 11955003
TI  - Phosphates, DNA, and the search for nonterrean life: a second generation model
      for genetic molecules.
AB  - Phosphate groups are found and used widely in biological chemistry. We have asked
      whether phosphate groups are likely to be important to the functioning of genetic
      molecules, including DNA and RNA. From observations made on synthetic analogs of
      DNA and RNA where the phosphates are replaced by nonanionic linking groups, we
      infer a set of rules that highlight the importance of the phosphodiester backbone
      for the proper functioning of DNA as a genetic molecule. The polyanionic backbone
      appears to give DNA the capability of replication following simple rules, and
      evolving. The polyanionic nature of the backbone appears to be critical to
      prevent the single strands from folding, permitting them to act as templates,
      guiding the interaction between two strands to form a duplex in a way that
      permits simple rules to guide the molecular recognition event, and buffering the
      sensitivity of its physicochemical properties to changes in sequence. We argue
      that the feature of a polyelectrolyte (polyanion or polycation) may be required
      for a "self-sustaining chemical system capable of Darwinian evolution." The
      polyelectrolyte structure therefore may be a universal signature of life,
      regardless of its genesis, and unique to living forms as well.

PMID- 11955004
TI  - A cytosolic tRNA with an unmodified adenosine in the wobble position reads a
      codon ending with the non-complementary nucleoside cytidine.
AB  - Out of more than 500 sequenced cytosolic tRNAs, there is only one with an
      unmodified adenosine in the wobble position (position 34). The reason for this
      rare occurrence of A34 is that it is mostly deaminated to inosine-34 (I34). I34
      is a common constituent in the wobble position of tRNAs and has a decoding
      capacity different from that of A34. We have isolated a mutant (proL207) of
      Salmonella typhimurium, in which the wobble nucleoside G34 has been replaced by
      an unmodified A in tRNA(Pro)(GGG), which is the only tRNA that normally reads the
      CCC codon. Thus, this mutant apparently has no tRNA that is considered cognate
      for the codon CCC. Despite this, the mutant grows normally. As expected, Pro-tRNA
      selection at the CCC codon in the A-site in a mutant deleted for the proL gene,
      which encodes the tRNA(Pro)(GGG), was severely reduced. However, in comparison
      this rate of selection was only slightly reduced in the proL207 mutant with its
      A34 containing tRNA(Pro)(AGG) suggesting that this tRNA reads CCC. Moreover,
      measurements of the interference by a tRNA residing in the P-site on the apparent
      termination efficiency at the A-site indicated that indeed the A34 containing
      tRNA reads the CCC codon. We conclude that A34 in a cytosolic tRNA is not
      detrimental to the cell and that the mutant tRNA(Pro)(AGG) is able to read the
      CCC codon like its wild-type counterpart tRNA(Pro)(GGG). We suggest that the
      decoding of the CCC codon by a 5'-AGG-3' anticodon occurs by a wobble base-pair
      between a protonated A34 and a C in the mRNA.

PMID- 11955005
TI  - RNA simulations: probing hairpin unfolding and the dynamics of a GNRA tetraloop.
AB  - Simulations of an RNA hairpin containing a GNRA tetraloop were conducted to allow
      the characterization of its secondary structure formation and dynamics. Ten 10 ns
      trajectories of the folded hairpin 5'-GGGC[GCAA]GCCU-3' were generated using
      stochastic dynamics and the GB/SA implicit solvent model at 300 K. Overall, we
      find the stem to be a very stable subunit of this molecule, whereas multiple loop
      conformations and transitions between them were observed. These trajectories
      strongly suggest that extension of the C6 base away from the loop occurs
      cooperatively with an N-type-->S-type sugar pucker conversion in that residue and
      that similar pucker transitions are necessary to stabilize other looped-out
      bases. In addition, a short-lived conformer with an extended fourth loop residue
      (A8) lacking this stabilizing 2'-endo pucker mode was observed. Results of
      thermal perturbation at 400 K support this model of loop dynamics. Unfolding
      trajectories were produced using this same methodology at temperatures of 500 to
      700 K. The observed unfolding events display three-state behavior kinetically
      (including native, globular, and unfolded populations) and, based on these
      observations, we propose a folding mechanism that consists of three distinct
      events: (i) collapse of the random unfolded structure and sampling of the
      globular state; (ii) passage into the folded region of configurational space as
      stem base-pairs form and gain helicity; and (iii) attainment of proper loop
      geometry and organization of loop pairing and stacking interactions. These
      results are considered in the context of current experimental knowledge of this
      and similar nucleic acid hairpins.

PMID- 11955006
TI  - The linkage between magnesium binding and RNA folding.
AB  - Understanding the linkage between Mg(2+) binding and RNA folding requires a
      proper theoretical model describing the energetics of Mg(2+) binding to the
      folded and unfolded states of RNA. Our current understanding of Mg(2+) binding to
      these different RNA states derives from empirical thermodynamic models that
      depend on a number of unjustified assumptions. We present a rigorous theoretical
      model describing the linkage between RNA folding and magnesium ion binding. In
      this model, based on the non-linear Poisson-Boltzmann (NLPB) equation, the
      stabilization of RNA by Mg(2+) arises from two distinct binding modes, diffuse
      binding and site binding. Diffusely bound Mg(2+) are described as an ensemble of
      hydrated ions that are attracted to the negative charge of the RNA. Site-bound
      Mg(2+) are partially desolvated ions that are attracted to electronegative
      pockets on the RNA surface. We explore two systems, yeast tRNA(Phe) and a 58
      nucleotide rRNA fragment, with different Mg(2+) binding properties. The NLPB
      equation accurately describes both the stoichiometric and energetic linkage
      between Mg(2+) binding and RNA folding for both of these systems without
      requiring any fitted parameters in the calculation. Moreover, the NLPB model
      presents a well-defined physical description of how Mg(2+) binding helps fold an
      RNA. For both of the molecules studied here, the relevant unfolded state is a
      disordered intermediate state (I) that contains stable helical secondary
      structure without any tertiary contacts. Diffusely bound Mg(2+) interact with
      these secondary structure elements to stabilize the I state. The secondary
      structural elements of the I state fold into a compact, native tertiary structure
      (the N state). Diffuse binding plays a dominant role in stabilizing the N state
      for both RNAs studied. However, for the rRNA fragment, site-binding to a location
      with extraordinarily high electrostatic potential is also coupled to folding. Our
      results suggest that much experimental data measuring the linkage between Mg(2+)
      binding and RNA folding must be reinterpreted.

PMID- 11955007
TI  - N-terminal N-myristoylation of proteins: refinement of the sequence motif and its
      taxon-specific differences.
AB  - N-terminal N-myristoylation is a lipid anchor modification of eukaryotic and
      viral proteins targeting them to membrane locations, thus changing the cellular
      function of modified proteins. Protein myristoylation is critical in many
      pathways; e.g. in signal transduction, apoptosis, or alternative extracellular
      protein export. The myristoyl-CoA:protein N-myristoyltransferase (NMT) recognizes
      the sequence motif of appropriate substrate proteins at the N terminus and
      attaches the lipid moiety to the absolutely required N-terminal glycine residue.
      Reliable recognition of capacity for N-terminal myristoylation from the substrate
      protein sequence alone is desirable for proteome-wide function annotation
      projects but the existing PROSITE motif is not practical, since it produces huge
      numbers of false positive and even some false negative predictions. As a first
      step towards a new prediction method, it is necessary to refine the sequence
      motif coding for N-terminal N-myristoylation. Relying on the in-depth study of
      the amino acid sequence variability of substrate proteins, on binding site
      analyses in X-ray structures or 3D homology models for NMTs from various taxa,
      and on consideration of biochemical data extracted from the scientific
      literature, we found indications that, at least within a complete substrate
      protein, the N-terminal 17 protein residues experience different types of
      variability restrictions. We identified three motif regions: region 1 (positions
      1-6) fitting the binding pocket; region 2 (positions 7-10) interacting with the
      NMT's surface at the mouth of the catalytic cavity; and region 3 (positions 11
      17) comprising a hydrophilic linker. Each region was characterized by physical
      requirements to single sequence positions or groups of positions regarding
      volume, polarity, backbone flexibility and other typical properties of amino
      acids (http://mendel.imp.univie.ac.at/myristate/). These specificity differences
      are confined partly to taxonomic ranges and are proposed for the design of NMT
      inhibitors in pathogenic fungal and protozoan systems including Aspergillus
      fumigatus, Leishmania major, Trypanosoma cruzi, Trypanosoma brucei, Giardia
      intestinalis, Entamoeba histolytica, Pneumocystis carinii, Strongyloides
      stercoralis and Schistosoma mansoni. An exhaustive search for NMT-homologues led
      to the discovery of two putative entomopoxviral NMTs.

PMID- 11955008
TI  - N-terminal N-myristoylation of proteins: prediction of substrate proteins from
      amino acid sequence.
AB  - Myristoylation by the myristoyl-CoA:protein N-myristoyltransferase (NMT) is an
      important lipid anchor modification of eukaryotic and viral proteins. Automated
      prediction of N-terminal N-myristoylation from the substrate protein sequence
      alone is necessary for large-scale sequence annotation projects but it requires a
      low rate of false positive hits in addition to a sufficient sensitivity. Our
      previous analysis of substrate protein sequence variability, NMT sequences and 3D
      structures has revealed motif properties in addition to the known PROSITE motif
      that are utilized in a new predictor described here. The composite prediction
      function (with separate ad hoc parameterization (a) for queries from non-fungal
      eukaryotes and their viruses and (b) for sequences from fungal species) consists
      of terms evaluating amino acid type preferences at sequences positions close to
      the N terminus as well as terms penalizing deviations from the physical property
      pattern of amino acid side-chains encoded in multi-residue correlation within the
      motif sequence. The algorithm has been validated with a self-consistency and two
      jack-knife tests for the learning set as well as with kinetic data for model
      substrates. The sensitivity in recognizing documented NMT substrates is above 95
      % for both taxon-specific versions. The corresponding rate of false positive
      prediction (for sequences with an N-terminal glycine residue) is close to 0.5 %;
      thus, the technique is applicable for large-scale automated sequence database
      annotation. The predictor is available as public WWW-server with the URL
      http://mendel.imp.univie.ac.at/myristate/. Additionally, we propose a version of
      the predictor that identifies a number of proteolytic protein processing sites at
      internal glycine residues and that evaluates possible N-terminal myristoylation
      of the protein fragments.A scan of public protein databases revealed new
      potential NMT targets for which the myristoyl modification may be of critical
      importance for biological function. Among others, the list includes kinases,
      phosphatases, proteasomal regulatory subunit 4, kinase interacting proteins
      KIP1/KIP2, protozoan flagellar proteins, homologues of mitochondrial translocase
      TOM40, of the neuronal calcium sensor NCS-1 and of the cytochrome c-type heme
      lyase CCHL. Analyses of complete eukaryote genomes indicate that about 0.5 % of
      all encoded proteins are apparent NMT substrates except for a higher fraction in
      Arabidopsis thaliana ( approximately 0.8 %).

PMID- 11955009
TI  - The folding pathway of the genomic hepatitis delta virus ribozyme is dominated by
      slow folding of the pseudoknots.
AB  - Hepatitis delta virus (HDV) replicates by a double rolling-circle mechanism that
      requires self-cleavage by closely related genomic and antigenomic versions of a
      ribozyme. We have previously shown that the uncleaved genomic ribozyme is subject
      to a variety of alternative (Alt) pairings. Sequence upstream of the ribozyme can
      regulate self-cleavage activity by formation of an Alt 1 ribozyme-containing
      structure that severely inhibits self-cleavage, or a P(-1) self-structure that
      permits rapid self-cleavage. Here, we test three other alternative pairings: Alt
      P1, Alt 2, and Alt 3. Alt P1 and Alt 3 contain primarily ribozyme-ribozyme
      interactions, while Alt 2 involves ribozyme-flanking sequence interaction. A
      number of single and double mutant ribozymes were prepared to increase or
      decrease the stability of the alternative pairings, and rates of self-cleavage
      were determined. Results of these experiments were consistent with the existence
      of the proposed alternative pairings and their ability to inhibit the overall
      rate of native ribozyme folding. Local misfolds are treated as internal
      equilibrium constants in a binding polynomial that modulates the intrinsic rate
      of cleavage. This model of equilibrium effects of misfolds should be general and
      apply to other ribozymes. All of the alternative pairings sequester a pseudoknot
      forming strand. Folding of ribozymes containing Alt P1 and Alt 2 was accelerated
      by urea as long as the native ribozyme fold was sufficiently stable, while
      folding of mutants in which both of these alternative pairings had been removed
      were not stimulated by urea. This behavior suggests that the pseudoknots form by
      capture of an unfolded or appropriately rearranged alternative pairing by its
      complementary native strand. Fast-folding mutants were prepared by either
      weakening alternative pairings or by strengthening native pairings. A kinetic
      model was developed that accommodates these features and explains the position of
      the rate-limiting step for the G11C mutant. Implications of these results for
      structural and dynamic studies of the uncleaved HDV ribozyme are discussed.

PMID- 11955010
TI  - The role of MeH73 in actin polymerization and ATP hydrolysis.
AB  - In actin from many species H73 is methylated, but the function of this rare post
      translational modification is unknown. Although not within bonding distance, it
      is located close to the gamma-phosphate of the actin-bound ATP. In most crystal
      structures of actin, the delta1-nitrogen of the methylated H73 forms a hydrogen
      bond with the carbonyl of G158. This hydrogen bond spans the gap separating
      subdomains 2 and 4, thereby contributing to the forces that close the interdomain
      cleft around the ATP polyphosphate tail. A second hydrogen bond stabilizing
      interdomain closure exists between R183 and Y69. In the closed-to-open transition
      in beta-actin, both of these hydrogen bonds are broken as the phosphate tail is
      exposed to solvent. Here we describe the isolation and characterization of a
      mutant beta-actin (H73A) expressed in the yeast Saccharomyces cerevisiae. The
      properties of the mutant are compared to those of wild-type beta-actin, also
      expressed in yeast. Yeast does not have the methyl transferase necessary to
      methylate recombinant beta-actin. Thus, the polymerization properties of yeast
      expressed wild-type beta-actin can be compared with normally methylated beta
      actin isolated from calf thymus. Since earlier studies of the actin ATPase almost
      invariably employed rabbit skeletal alpha-actin, this isoform was included in
      these comparative studies on the polymerization, ATP hydrolysis, and phosphate
      release of actin. It was found that H73A-actin exchanged ATP at an increased
      rate, and was less stable than yeast-expressed wild-type actin, indicating that
      the mutation affects the spatial relationship between the two domains of actin
      which embrace the nucleotide. At physiological concentrations of Mg(2+), the
      kinetics of ATP hydrolysis of the mutant actin were unaffected, but polymer
      formation was delayed. The comparison of methylated and unmethylated beta-actin
      revealed that in the absence of a methyl group on H73, ATP hydrolysis and
      phosphate release occurred prior to, and seemingly independently of, filament
      formation. The comparison of beta and alpha-actin revealed differences in the
      timing and relative rates of ATP hydrolysis and P(i)-release.

PMID- 11955011
TI  - Oligomeric state of membrane transport proteins analyzed with blue native
      electrophoresis and analytical ultracentrifugation.
AB  - Blue native electrophoresis is used widely for the analysis of non-dissociated
      protein complexes with respect to composition, oligomeric state and molecular
      mass. However, the effects of detergent or dye binding on the mass and stability
      of the integral membrane proteins have not been studied. By comparison with
      analytical ultracentrifugation, we have evaluated whether the oligomeric state of
      membrane transport proteins is reflected reliably with blue native
      electrophoresis. For the analysis we have used two well-characterized
      transporters, that is, the major facilitator superfamily protein LacS and the
      phosphotransferase system EII(Mtl). For another member of the major facilitator
      superfamily, the xyloside transporter XylP from Lactobacillus pentosus, the
      complete analysis of the quaternary structure determined by analytical
      ultracentrifugation and freeze-fracture electron microscopy is presented. Our
      experiments show that during blue native electrophoresis the detergent bound to
      the proteins is replaced by the amphipathic Coomassie brilliant blue (CBB) dye.
      The mass of the bound CBB dye was quantified. Provided this additional mass of
      bound CBB dye is accounted for and care is taken in the choice and concentration
      of the detergent used, the mass of LacS, XylP and EII(Mtl) and four other
      membrane (transport) proteins could be deduced within 10 % error. Our data
      underscore the fact that the oligomeric state of many membrane transport proteins
      is dimeric.

PMID- 11955012
TI  - Exploring the role of alanine in the structure of the Lac repressor
      tetramerization domain, a ferritin-like Alacoil.
AB  - We are interested in the determinants that specify the structure of antiparallel
      coiled coils. Antiparallel coiled coils often contain alanine as an important
      interfacial packing residue; structures containing alanine at certain well
      defined positions in the heptad-repeating unit are referred to as Alacoils. Two
      types have been identified, containing alanine at either the g position of the
      heptad repeating unit (defined as the d position in the Richardson nomenclature),
      referred to as a rop-like Alacoil, or the e position (a position in the
      Richardson nomenclature), referred to as a ferritin-like Alacoil. The Lac
      repressor tetramerization domain forms an antiparallel four-chain coiled coil,
      which falls into the second class of Alacoils based on recent crystal structures.
      The role of alanine in such structures has not yet been explored experimentally.
      We test the importance of alanine at the e positions on the oligomeric state and
      stability of the isolated coiled-coil domain of Lac repressor by testing the
      effect of mutations at this position. We find that mutation to leucine is
      tolerated and its moderately stabilizing effect is most likely a consequence of
      plasticity of this motif. The effects on stability of the mutations to either
      serine or glutamine can be largely accounted for by helix propensity differences
      between these residues and alanine. The ability of the helices to adjust to such
      mutations, while maintaining the basic fold of this coiled coil, was further
      tested by making the same changes at the more highly exposed g position. Leucine
      at the g positions also causes an increase in stability, presumably by subtle
      rearrangement of the helices to allow partial desolvation of this side-chain.

PMID- 11955013
TI  - Conformational plasticity in folding of the split beta-alpha-beta protein S6:
      evidence for burst-phase disruption of the native state.
AB  - An increasing number of folding studies of two-state proteins shows that point
      mutations sometimes change the kinetic m-values, leading to kinks and curves in
      the chevron plots. The molecular origin of these changes is yet unclear although
      it is speculated that they are linked to structural rearrangement of the
      transition state or to accumulation of meta-stable intermediates. To shed more
      light on this issue, we present here a combined m and phi-value analysis of the
      split beta-alpha-beta protein S6. Wild-type S6 displays classical two-state
      kinetics with v-shaped chevron plot, but a majority of its mutants display
      distinct m-value changes or curved chevrons. We observe that this kinetic
      aberration of S6 is linked to mutations that are clustered in distinct regions of
      the native structure. The most pronounced changes, i.e. decrease in the m-value
      for the unfolding rate constant, are seen upon truncation of interactions between
      the N and C termini, whereas mutations in the centre of the hydrophobic core show
      smaller or even opposed effects. As a consequence, the calculated phi-values
      display a systematic increase upon addition of denaturant. In the case of S6, the
      phenomenon seems to arise from a general plasticity of the different species on
      the folding pathway. That is, the structure of the denatured ensemble, the
      transition state, and the native ground-state for unfolding seem to change upon
      mutation. From these changes, it is concluded that interactions spanning the
      centre of the hydrophobic core form early in folding, whereas the entropically
      disfavoured interactions linking the N and C termini consolidate very late,
      mainly on the down-hill-side of the folding barrier.

PMID- 11955014
TI  - Direct probing of RNA structure and RNA-protein interactions in purified HeLa
      cell's and yeast spliceosomal U4/U6.U5 tri-snRNP particles.
AB  - The U4/U6.U5 tri-snRNP is a key component of spliceosomes. By using chemical
      reagents and RNases, we performed the first extensive experimental analysis of
      the structure and accessibility of U4 and U6 snRNAs in tri-snRNPs. These were
      purified from HeLa cell nuclear extract and Saccharomyces cerevisiae cellular
      extract. U5 accessibility was also investigated. For both species, data
      demonstrate the formation of the U4/U6 Y-shaped structure. In the human tri-snRNP
      and U4/U6 snRNP, U6 forms the long range interaction, that was previously
      proposed to be responsible for dissociation of the deproteinized U4/U6 duplex. In
      both yeast and human tri-snRNPs, U5 is more protected than U4 and U6, suggesting
      that the U5 snRNP-specific protein complex and other components of the tri-snRNP
      wrapped the 5' stem-loop of U5. Loop I of U5 is partially accessible, and
      chemical modifications of loop I were identical in yeast and human tri-snRNPs.
      This reflects a strong conservation of the interactions of proteins with the
      functional loop I. Only some parts of the U4/U6 Y-shaped motif (the 5' stem-loop
      of U4 and helix II) are protected. Due to difference of protein composition of
      yeast and human tri-snRNP, the U6 segment linking the 5' stem-loop to the Y
      shaped structure and the U4 central single-stranded segment are more accessible
      in the yeast than in the human tri-snRNP, especially, the phylogenetically
      conserved ACAGAG sequence of U6. Data are discussed taking into account knowledge
      on RNA and protein components of yeast and human snRNPs and their involvement in
      splicesome assembly.

PMID- 11955015
TI  - Polymerase beta simulations suggest that Arg258 rotation is a slow step rather
      than large subdomain motions per se.
AB  - The large-scale opening motion of mammalian DNA polymerase beta is followed at
      atomic resolution by dynamic simulations that link crystal "closed" and "open"
      conformations. The closing/opening conformational change is thought to be key to
      the ability of polymerases to choose a correct nucleotide (through "induced fit")
      and hence maintain DNA repair synthesis fidelity. Corroborating available
      structural and kinetic measurements, our studies bridge static microscopic
      crystal structures with macroscopic kinetic data by delineating a specific
      sequence, Phe272 ring flip, large thumb movement, Arg258 rotation with release of
      catalytic Mg2+, together with estimated time-scales, that suggest the Arg258
      rearrangement as a limiting factor of large subdomain motions. If similarly slow
      in the closing motion, this conformational change might be restricted further
      when an incorrect nucleotide binds and thus play a role in pol beta's selectivity
      for the correct nucleotide. These results suggest new lines of experimentation in
      the study of polymerase mechanisms (e.g. enzyme mutants), which should provide
      further insights into mechanisms of error discrimination and DNA synthesis
      fidelity.

PMID- 11955016
TI  - Electron cryo-microscopy of VAT, the archaeal p97/CDC48 homologue from
      Thermoplasma acidophilum.
AB  - VAT (valosine containing protein-like ATPase from Thermoplasma acidophilum), an
      archaeal member of the AAA-family (ATPases associated with a variety of cellular
      activities) that possesses foldase as well as unfoldase-activity, forms homo
      hexameric rings like its eukaryotic homologues p97 and CDC48. The VAT-monomer
      exhibits the tripartite domain architecture typical for type II AAA-ATPases: N-D1
      D2, whereby N is the substrate binding N-terminal domain preceding domains D1 and
      D2, both containing AAA-modules. Recent 3-D reconstructions of VAT and p97 as
      obtained by electron microscopy suffer from weakly represented N-domains,
      probably a consequence of their flexible linkage to the hexameric core. Here we
      used electron cryo-microscopy and 3-D reconstruction of single particles in order
      to generate a 3-D model of VAT at 2.3 nm resolution. The hexameric core of the
      VAT-complex (diameter 13.2 nm, height 8.4 nm) encloses a central cavity and the
      substrate-binding N-domains are clearly arranged in the upper periphery.
      Comparison with the p97 3-D reconstruction and the recently determined crystal
      structure of p97-N-D1 suggests a tail-to-tail arrangement of D1 and D2 in VAT.

PMID- 11955017
TI  - Transthyretin fibrillogenesis entails the assembly of monomers: a molecular model
      for in vitro assembled transthyretin amyloid-like fibrils.
AB  - Extracellular accumulation of transthyretin (TTR) variants in the form of
      fibrillar amyloid deposits is the pathological hallmark of familial amyloidotic
      polyneuropathy (FAP). The TTR Leu55Pro variant occurs in the most aggressive
      forms of this disease. Inhibition of TTR wild-type (WT) and particularly TTR
      Leu55Pro fibril formation is of interest as a potential therapeutic strategy and
      requires a thorough understanding of the fibril assembly mechanism. To this end,
      we report on the in vitro assembly properties as observed by transmission
      electron microscopy (TEM), atomic force microscopy (AFM) and quantitative
      scanning transmission electron microscopy (STEM) for both TTR WT fibrils produced
      by acidification, and TTR Leu55Pro fibrils assembled at physiological pH. The
      morphological features and dimensions of TTR WT and TTR Leu55Pro fibrils were
      similar, with up to 300 nm long, 8 nm wide fibrils being the most prominent
      species in both cases. Other species were evident; 4-5 nm wide fibrils, 9-10 nm
      wide fibrils and oligomers of various sizes. STEM mass-per-length (MPL)
      measurements revealed discrete fibril types with masses of 9.5 and 14.0(+/-1.4)
      KDa/nm for TTR WT fibrils and 13.7, 18.5 and 23.2(+/-1.5) kDa/nm for TTR Leu55Pro
      fibrils. These MPL values are consistent with a model in which fibrillar TTR
      structures are composed of two, three, four or five elementary protofilaments,
      with each protofilament being a vertical stack of structurally modified TTR
      monomers assembled with the 2.9 nm axial monomer-monomer spacing indicated by X
      ray fibre diffraction data. Ex vivo TTR amyloid fibrils were examined. From their
      morphological appearance compared to these, the in vitro assembled TTR WT and
      Leu55Pro fibrils examined may represent immature fibrillar species. The in vitro
      system operating at physiological pH for TTR Leu55Pro and the model presented for
      the molecular arrangement of TTR monomers within fibrils may, therefore, describe
      early fibril assembly events in vivo.

PMID- 11955018
TI  - Localization of uroplakin Ia, the urothelial receptor for bacterial adhesin FimH,
      on the six inner domains of the 16 nm urothelial plaque particle.
AB  - The binding of uropathogenic Escherichia coli to the urothelial surface is a
      critical initial event for establishing urinary tract infection, because it
      prevents the bacteria from being removed by micturition and it triggers bacterial
      invasion as well as host cell defense. This binding is mediated by the FimH
      adhesin located at the tip of the bacterial type 1-fimbrium and its urothelial
      receptor, uroplakin Ia (UPIa). To localize the UPIa receptor on the 16 nm
      particles that form two-dimensional crystals of asymmetric unit membrane (AUM)
      covering >90 % of the apical urothelial surface, we constructed a 15 A resolution
      3-D model of the mouse 16 nm AUM particle by negative staining and electron
      crystallography. Similar to previous lower-resolution models of bovine and pig
      AUM particles, the mouse 16 nm AUM particle consists of six inner and six outer
      domains that are interconnected to form a twisted ribbon-like structure.
      Treatment of urothelial plaques with 0.02-0.1 % (v/v) Triton X-100 allowed the
      stain to penetrate into the membrane, revealing parts of the uroplakin
      transmembrane moiety with an overall diameter of 14 nm, which was much bigger
      than the 11 nm value determined earlier by quick-freeze deep-etch. Atomic force
      microscopy of native, unfixed mouse and bovine urothelial plaques confirmed the
      overall structure of the luminal 16 nm AUM particle that was raised by 6.5 nm
      above the luminal membrane surface and, in addition, revealed a circular, 0.5 nm
      high, cytoplasmic protrusion of approximately 14 nm diameter. Finally, a
      difference map calculated from the mouse urothelial plaque images collected in
      the presence and absence of recombinant bacterial FimH/FimC complex revealed the
      selective binding of FimH to the six inner domains of the 16 nm AUM particle.
      These results indicate that the 16 nm AUM particle is anchored by a approximately
      14 nm diameter transmembrane stalk, and suggest that bacterial binding to UPIa
      that resides within the six inner domains of the 16 nm AUM particle may
      preferentially trigger transmembrane signaling involved in bacterial invasion and
      host cell defense.

PMID- 11955019
TI  - States of thin filament regulatory proteins as revealed by combined cross
      linking/X-ray diffraction techniques.
AB  - The regulatory protein system in the skeletal muscle thin filaments is known to
      exhibit three discrete states, called "off" or "blocked" (no Ca2+), "on" or
      "closed" (with Ca2+ alone) and "potentiated" or "open" (with strongly bound
      myosin head) states. Biochemical studies have shown that only weak interactions
      with myosin are allowed in the second state. Characterization of each state is
      often difficult, because the equilibria among these states are readily shifted by
      experimental conditions. To overcome this problem, we chemically cross-linked the
      skeletal muscle thin filament in the three states with the zero-length cross
      linker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), in overstretched
      muscle fibers. The state of the regulatory proteins was monitored by measuring
      the intensity of the second actin layer-line (2nd LL) reflection in X-ray
      diffraction patterns. Structurally, the thin filaments cross-linked in the three
      states exhibited three corresponding discrete levels of 2nd LL intensities, which
      were not Ca2+-sensitive any more. Functionally, the thin filament cross-linked in
      the "off-blocked" state inhibited strong interaction with myosin head
      (subgfragment-1 or S1). The thin filament cross-linked in the "potentiated-open"
      state allowed strong interaction and full ATPase activity of S1 as described
      previously. The thin filament cross-linked in the "on-closed" state allowed
      strong interactions with S1 and actin-activated ATPase without enhancing the 2nd
      LL to the level of "potentiated-open" state, contrary to the expectations from
      the biochemical studies. The results demonstrate the potential of EDC as a tool
      for studying the states of calcium regulation, and the apparent uncoupling
      between the 2nd LL intensity and the function provides a new insight into the
      mechanism of thin filament regulation.

PMID- 11955020
TI  - Stiffness of the distal loop restricts the structural heterogeneity of the
      transition state ensemble in SH3 domains.
AB  - Protein engineering experiments and Phi(F)-value analysis of SH3 domains reveal
      that their transition state ensemble (TSE) is conformationally restricted, i.e.
      the fluctuations in the transition state (TS) structures are small. In the TS of
      src SH3 and alpha-spectrin SH3 the distal loop and the associated hairpin are
      fully structured, while the rest of the protein is relatively disordered. If
      native structure predominantly determines the folding mechanism, the findings for
      SH3 folds raise the question: What are the features of the native topology that
      determine the nature of the TSE? We propose that the presence of stiff loops in
      the native state that connect local structural elements (such as the distal
      hairpin in SH3 domains) conformationally restricts TSE. We validate this
      hypothesis using the simulations of a "control" system (16 residue beta-hairpin
      forming C-terminal fragment of the GBl protein) and its variants. In these
      fragments the role of bending rigidity in determining the nature of the TSE can
      be directly examined without complications arising from interactions with the
      rest of the protein. The TSE structures in the beta-hairpins are determined
      computationally using cluster analysis and limited Phi(F)-value analysis. Both
      techniques prove that the conformational heterogeneity decreases as the bending
      rigidity of the loop increases. To extend this finding to SH3 domains a measure
      of bending rigidity based on loop curvature, which utilizes native structures in
      the Protein Data Bank (PDB), is introduced. Using this measure we show that, with
      few exceptions, the ordering of stiffness of the distal, n-src, and RT loops in
      the 29 PDB structures of SH3 domains is conserved. Combining the simulation
      results for beta-hairpins and the analysis of PDB structures for SH3 domains, we
      propose that the stiff distal loop restricts the conformational fluctuations in
      the TSE. We also predict that constraining the distal loop to be preformed in the
      denatured ensemble should not alter the nature of TSE. On the other hand, if the
      amino and carboxy terminals are cross-linked to form a circular polypeptide
      chain, the pathways and TSs are altered. These contrasting scenarios are
      illustrated using simulations of cross-linked WT beta-hairpin fragments.
      Computations of bending rigidities for immunoglobulin-like domain proteins reveal
      no clear separation in the stiffness of their loops. In the beta-sandwich
      proteins, which have large fractions of non-local native contacts, the nature of
      the TSE cannot be apparently determined using purely local structural
      characteristics. Nevertheless, the measure of loop stiffness still provides
      qualitative predictions of the ordered regions in the TSE of Ig27 and TenFn3.

PMID- 11955021
TI  - Temperature-dependence of protein hydrogen bond properties as studied by high
      resolution NMR.
AB  - The temperature-dependence of a large number of NMR parameters describing
      hydrogen bond properties in the protein ubiquitin was followed over a range from
      5 to 65 degrees C. The parameters comprise hydrogen bond (H-bond) scalar
      couplings, h3JNC', chemical shifts, amide proton exchange rates, 15N relaxation
      parameters as well as covalent 1JNC' and 1JNH couplings. A global weakening of
      the h3JNC' coupling with increasing temperature is accompanied by a global
      upfield shift of the amide protons and a decrease of the sequential 1JNC'
      couplings. If interpreted as a linear increase of the N...O distance, the change
      in h3JNC' corresponds to an average linear thermal expansion coefficient for the
      NH-->O hydrogen bonds of 1.7 x 10(-4)/K, which is in good agreement with overall
      volume expansion coefficients observed for proteins. A residue-specific analysis
      reveals that not all hydrogen bonds are affected to the same extent by the
      thermal expansion. The end of beta-sheet beta1/beta5 at hydrogen bond E64-->Q2
      appears as the most thermolabile, whereas the adjacent hydrogen bond I3-->L15
      connecting beta-strands beta1 and beta2 is even stabilized slightly at higher
      temperatures. Additional evidence for the stabilization of the beta1/beta2 beta
      hairpin at higher temperatures is found in reduced hydrogen exchange rates for
      strand end residue V17. This reduction corresponds to a stabilizing change in
      free energy of 9.7 kJ/mol for the beta1/beta2 hairpin. The result can be linked
      to the finding that the beta1/beta2 hairpin behaves as an autonomously folding
      unit in the A-state of ubiquitin under changed solvent conditions. For several
      amide groups the temperature-dependencies of the amide exchange rates and H-bond
      scalar couplings are uncorrelated. Therefore, amide exchange rates are not a sole
      function of the hydrogen bond "strength" as given by the electronic overlap of
      donors and acceptors, but are clearly dependent on other blocking mechanisms.

PMID- 11955022
TI  - An expectation maximization algorithm for training hidden substitution models.
AB  - We derive an expectation maximization algorithm for maximum-likelihood training
      of substitution rate matrices from multiple sequence alignments. The algorithm
      can be used to train hidden substitution models, where the structural context of
      a residue is treated as a hidden variable that can evolve over time. We used the
      algorithm to train hidden substitution matrices on protein alignments in the Pfam
      database. Measuring the accuracy of multiple alignment algorithms with reference
      to BAliBASE (a database of structural reference alignments) our substitution
      matrices consistently outperform the PAM series, with the improvement steadily
      increasing as up to four hidden site classes are added. We discuss several
      applications of this algorithm in bioinformatics.

PMID- 11955023
TI  - Mutagenic mapping of helical structures in the transmembrane segments of the
      yeast alpha-factor receptor.
AB  - The alpha-mating pheromone receptor encoded by the yeast STE2 gene is a G protein
      coupled receptor that initiates signaling via a MAP kinase pathway that prepares
      haploid cells for mating. To establish the range of allowed amino acid
      substitutions within transmembrane segments of this receptor, we conducted
      extensive random mutagenesis of receptors followed by screening for receptor
      function. A total of 157 amino acid positions in seven different mutagenic
      libraries corresponding to the seven predicted transmembrane segments were
      analyzed, yielding 390 alleles that retain at least 60 % of normal signaling
      function. These alleles contained a total of 576 unique amino acid substitutions,
      including 61 % of all the possible amino acid changes that can arise from single
      base substitutions. The receptor exhibits a surprising tolerance for amino acid
      substitutions. Every amino acid in the mutagenized regions of the transmembrane
      regions could be substituted by at least one other residue. Polar amino acids
      were tolerated in functional receptors at 115 different positions (73 % of the
      total). Hydrophobic amino acids were tolerated in functional receptors at all
      mutagenized positions. Substitutions introducing proline residues were recovered
      at 53 % of all positions where they could be brought about by single base
      changes. Residues with charged side-chains could also be tolerated at 53 % of all
      positions where they were accessible through single base changes. The spectrum of
      allowed amino acid substitutions was characterized in terms of the
      hydrophobicity, radius of gyration, and charge of the allowed substitutions and
      mapped onto alpha-helical structures. By comparing the patterns of allowed
      substitutions with the recently determined structure of rhodopsin, structural
      features indicative of helix-helix interactions can be discerned in spite of the
      extreme sequence divergence between these two proteins.

PMID- 11955024
TI  - A diabetes report card for the United States: quality of care in the 1990s.
AB  - BACKGROUND: Improving diabetes care in the United States is a topic of concern.
      OBJECTIVE: To document the quality of diabetes care during 1988-1995. DESIGN:
      National population-based cross-sectional surveys. SETTING: Third U.S. National
      Health and Nutrition Examination Survey (NHANES III) (1988-1994) and the
      Behavioral Risk Factors Surveillance System (BRFSS) (1995). PARTICIPANTS:
      Participants in NHANES III (n = 1026) or BRFSS (n = 3059) who were 18 to 75 years
      of age and reported a physician diagnosis of diabetes. Women with gestational
      diabetes were excluded. MEASUREMENTS: Glycemic control, blood pressure, low
      density lipoprotein (LDL) cholesterol level, biannual cholesterol monitoring, and
      annual foot and dilated eye examination, as defined by the Diabetes Quality
      Improvement Project. RESULTS: 18.0% of participants (95% CI, 15.7% to 22.3%) had
      poor glycemic control (hemoglobin A(1c) level > 9.5%), and 65.7% (CI, 62.0% to
      69.4%) had blood pressure less than 140/90 mm Hg. Cholesterol was monitored
      biannually in 85.3% (CI, 83.1% to 88.6%) of participants, but only 42.0% (CI,
      34.9% to 49.1%) had LDL cholesterol levels less than 3.4 mmol/L (<130 mg/dL).
      During the previous year, 63.3% (CI, 59.6% to 67.0%) had a dilated eye
      examination and 54.8% (CI, 51.3% to 58.3%) had a foot examination. When
      researchers controlled for age, sex, ethnicity, education, health insurance,
      insulin use, and duration of diabetes, insured persons were more likely than
      uninsured persons to have a dilated eye examination (66.5% [CI, 62.6% to 70.4%])
      vs. 43.2% [CI, 29.5% to 56.9%]) and were less likely to have a hemoglobin
      A(1c)level greater than or equal to 9.5%. Persons taking insulin were more likely
      than those who were not to have annual dilated eye examination (72.2% [CI, 66.3%
      to 78.1%] vs. 57.6% [CI, 53.7% to 61.5%]) and foot examination (67.3% [CI, 61.4%
      to 73.2%] vs. 47.1% [CI, 43.2% to 51.0%]) but were also more likely to have poor
      glycemic control (24.2% [CI, 18.3% to 30.1%] vs. 15.5% [CI, 11.6% to 19.4%]).
      CONCLUSIONS: According to U.S. data collected during 1988-1995, a gap exists
      between recommended diabetes care and the care patients actually receive. These
      data offer a benchmark for monitoring changes in diabetes care.

PMID- 11955025
TI  - Identification of persons at high risk for type 2 diabetes mellitus: do we need
      the oral glucose tolerance test?
AB  - BACKGROUND: The standard method of identifying persons at high risk for type 2
      diabetes mellitus involves detection of impaired glucose tolerance, which
      requires a costly and inconvenient 2-hour oral glucose tolerance test. Because
      clinical trials have indicated that diabetes is preventable by using behavioral
      or pharmacologic interventions, less expensive methods of identifying high-risk
      persons are needed. OBJECTIVE: To determine whether multivariable models are
      superior to glucose tolerance tests for identifying persons at high risk for
      diabetes mellitus. DESIGN: Prospective cohort study. SETTING: San Antonio, Texas.
      PARTICIPANTS: 1791 Mexican Americans and 1112 non-Hispanic whites without
      diabetes at baseline who were randomly selected from census tracts. MEASUREMENTS:
      Medical history; body mass index; blood pressure; fasting and 2-hour plasma
      glucose levels; fasting serum total, low-density lipoprotein, and high-density
      lipoprotein cholesterol levels; and triglyceride level. RESULTS: For prediction
      of 7.5-year incidence of type 2 diabetes, the area under the receiver-operating
      characteristic (ROC) curve for a multivariable model involving readily available
      clinical variables was significantly (P < 0.001) greater than the area under the
      ROC curve for the 2-hour glucose value alone (84.3% vs. 77.5%). Impaired glucose
      tolerance represents a single point on the latter curve. Adding the 2-hour
      glucose measurement to the multivariable model increased the area under its ROC
      curve, but only from 84.3% to 85.7%. CONCLUSION: Persons at high risk for
      diabetes mellitus are better identified by using a simple prediction model than
      by relying exclusively on the results of a 2-hour oral glucose tolerance test.
      Although adding the 2-hour glucose variable to the model enhanced prediction, the
      resulting slight improvement entails greater cost and inconvenience.

PMID- 11955026
TI  - High risk for hyperlipidemia and the metabolic syndrome after an episode of
      hypertriglyceridemia during 13-cis retinoic acid therapy for acne: a
      pharmacogenetic study.
AB  - BACKGROUND: Administration of 13-cis retinoic acid (isotretinoin) for acne is
      occasionally accompanied by hyperlipidemia. It is not known why some persons
      develop this side effect. OBJECTIVE: To determine whether isotretinoin triggers a
      familial susceptibility to hyperlipidemia and the metabolic syndrome. DESIGN:
      Cross-sectional comparison. SETTING: University hospital in Lausanne,
      Switzerland. PARTICIPANTS: 102 persons in whom triglyceride levels increased at
      least 1.0 mmol/L (> or =89 mg/dL) (hyperresponders) and 100 persons in whom
      triglyceride levels changed 0.1 mmol/L (< or =9 mg/dL) or less (nonresponders)
      during isotretinoin therapy for acne. Parents of 71 hyperresponders and 60
      nonresponders were also evaluated. MEASUREMENTS: Waist-to-hip ratio; fasting
      glucose, insulin, and lipid levels; and apoE genotype. RESULTS: Hyperresponders
      and nonresponders had similar pretreatment body weight and plasma lipid levels.
      When reevaluated approximately 4 years after completion of isotretinoin therapy,
      hyperresponders were more likely to have hypertriglyceridemia (triglyceride level
      > 2.0 mmol/L [>177 mg/dL]; odds ratio [OR], 4.8 [95% CI, 1.6 to 13.8]),
      hypercholesterolemia (cholesterol level > 6.5 mmol/L [>252 mg/dL]; OR, 9.1 [CI,
      1.9 to 43]), truncal obesity (waist-to-hip ratio > 0.90 [OR, 11.0 (CI, 2.0 to
      59]), and hyperinsulinemia (insulin-glucose ratio > 7.2; OR, 3.0 [CI, 1.6 to
      5.7]). In addition, more hyperresponders had at least one parent with
      hypertriglyceridemia (OR, 2.6 [CI, 1.2 to 5.7]) or a ratio of total to high
      density lipoprotein cholesterol that exceeded 4.0 (OR, 3.5 [CI, 1.5 to 8.0]).
      Lipid response to isotretinoin was closely associated with the apoE gene.
      CONCLUSION: Persons who develop hypertriglyceridemia during isotretinoin therapy
      for acne, as well as their parents, are at increased risk for future
      hyperlipidemia and the metabolic syndrome.

PMID- 11955027
TI  - Severe hepatotoxicity associated with the dietary supplement LipoKinetix.
AB  - BACKGROUND: LipoKinetix (Syntrax, Cape Girardeau, Missouri) is a dietary
      supplement marketed for weight loss. OBJECTIVE: To describe a possible causal
      association between LipoKinetix and hepatotoxicity. DESIGN: Case series. SETTING:
      Outpatient clinic, tertiary care hospital, and U.S. Food and Drug Administration
      databases. INTERVENTION: Routine medical and supportive care. MEASUREMENTS:
      Clinical and laboratory evaluation. RESULTS: All patients developed acute
      hepatotoxicity within 3 months of starting LipoKinetix. At presentation, symptoms
      and results of laboratory tests were characteristic of acute hepatitis. All
      patients recovered spontaneously after LipoKinetix use was discontinued. Three of
      the seven patients, including one who developed fulminant hepatic failure
      complicated by cerebral edema, were taking LipoKinetix alone at the time of
      presentation. Of the four patients who were taking multiple supplements, two
      resumed taking supplements other than LipoKinetix without incident. CONCLUSIONS:
      The use of LipoKinetix may be associated with hepatotoxicity. Despite extensive
      evaluations, no other cause for hepatotoxicity could be identified in the seven
      patients studied.

PMID- 11955028
TI  - Potential physician malpractice liability associated with complementary and
      integrative medical therapies.
AB  - Physicians are increasingly grappling with medical liability issues as
      complementary and integrative health care practices are made available in
      conventional medical settings. This article proposes a framework in which
      physicians can assess potential malpractice liability issues in counseling
      patients about complementary and integrative therapies. The framework classifies
      complementary and integrative therapies according to whether the evidence
      reported in the medical and scientific literature supports both safety and
      efficacy; supports safety, but evidence regarding efficacy is inconclusive;
      supports efficacy, but evidence regarding safety is inconclusive; or indicates
      either serious risk or inefficacy. Clinical examples in each category help guide
      the clinician on how to counsel patients regarding use of complementary and
      alternative medical therapies in a given clinical situation. Specific strategies
      to reduce the risk for potential malpractice liability include the following: 1)
      determine the clinical risk level; 2) document the literature supporting the
      therapeutic choice; 3) provide adequate informed consent; 4) continue to monitor
      the patient conventionally; and 5) for referrals, inquire about the competence of
      the complementary and alternative medicine provider. This framework provides a
      basis for clinical decisions involving complementary and integrative care.

PMID- 11955029
TI  - Chronic renal diseases: renoprotective benefits of renin-angiotensin system
      inhibition.
AB  - Progression to renal parenchymal damage and end-stage renal disease, which seems
      to be largely independent of the initial insult, is the final common pathway for
      chronic, proteinuric nephropathies in animals and humans. The key event is
      enhanced glomerular capillary pressure; this impairs glomerular permeability to
      proteins and permits excessive amounts of proteins to reach the lumen of the
      proximal tubule. The secondary process of reabsorption of filtered proteins can
      contribute to renal interstitial injury by activating intracellular events,
      including upregulation of the genes encoding vasoactive and inflammatory
      mediators. Both interstitial inflammation and progression of disease can be
      controlled by such drugs as angiotensin-converting enzyme inhibitors, which
      strengthen the glomerular permeability barrier to proteins and thereby limit
      proteinuria and filtered protein-dependent inflammatory signals. Clinical data
      strongly suggest that remission can now be achieved in some patients with chronic
      renal disease. Because of the current lag time between starting treatment and
      remission, however, a substantial proportion of patients still progress to end
      stage renal disease before renal function begins to stabilize. A multimodal
      approach that centers on reducing or removing all risk factors associated with
      the progression of renal disease may decrease the time to remission of the
      disease for most patients with proteinuric nephropathies.

PMID- 11955030
TI  - Balancing safety of dietary supplements with the free market.

PMID- 11955031
TI  - The role of high-dose chemotherapy and stem-cell transplantation in patients with
      multiple myeloma: a practice guideline of the Cancer Care Ontario Practice
      Guidelines Initiative.
AB  - The Hematology Disease Site Group of the Cancer Care Ontario Practice Guidelines
      Initiative has systematically reviewed the published literature and, through a
      consensus process, developed an evidence-based practice guideline assessing the
      role of stem-cell transplantation in patients with multiple myeloma. The
      conclusions were validated by solicited feedback from 221 practitioners across
      Ontario, Canada. The guideline comprises six recommendations: 1) Autologous
      transplantation is recommended for patients with stage II or III myeloma and good
      performance status. Evidence of benefit is strongest for patients who are younger
      than 55 years of age and have a serum creatinine level less than 150 micromol/L
      (<1.7 mg/dL). Physicians must use clinical judgment in recommending
      transplantation to other patients. 2) Allogeneic transplantation is not
      recommended as routine therapy. 3) Patients potentially eligible for
      transplantation should be referred for assessment early after diagnosis and
      should not be extensively exposed to alkylating agents before collection of stem
      cells. 4) Autologous peripheral blood stem cells should be harvested early in the
      patient's treatment course. The best available data suggest that transplantation
      is most advantageous when performed as part of initial therapy. 5) The
      comparative data addressing the specifics of the transplantation process are
      insufficient to allow definitive recommendations. In the absence of such data, a
      single transplant with high-dose melphalan, with or without total-body
      irradiation, is suggested for patients undergoing transplantation outside a
      clinical trial. 6) At this time, no conclusions can be reached about the role of
      interferon therapy after transplantation.

PMID- 11955032
TI  - Osteoarthritis and knee pain.

PMID- 11955034
TI  - Pseudoaccountability.

PMID- 11955035
TI  - Long-term prediction of coronary heart disease in young men.

PMID- 11955037
TI  - Appropriate antibiotic use for acute pharyngitis.

PMID- 11955038
TI  - Cardiovascular outcomes and renal disease.

PMID- 11955041
TI  - William of Occam and Occam's razor.

PMID- 11955042
TI  - Correction: cost-effectiveness of statins in older patients with myocardial
      infarction.

PMID- 11955043
TI  - Intimate-partner violence: the need for primary prevention in the community.

PMID- 11955044
TI  - Summary for patients. A diabetes report card for the United States, 1988-1995.

PMID- 11955045
TI  - Summary for patients. Identifying people at high risk for type 2 diabetes.

PMID- 11955046
TI  - Summary for patients. An unusual "side effect" of an acne drug.

PMID- 11955047
TI  - Summary for patients. Liver failure associated with the dietary supplement
      LipoKinetix.

PMID- 11955048
TI  - Role of cofactors in protein folding.
AB  - Although cofactors are essential components of many proteins to attain biological
      activity, the role of cofactors in protein folding is not well understood.
      Biophysical characterization of four types of cofactor-binding proteins (with
      copper, flavin moiety, iron-sulfur cluster, and heme cofactors, respectively)
      provides the following insights. (1) The presence of the cofactor often
      stabilizes the native protein. (2) The cofactor has the ability to interact
      specifically with the unfolded polypeptide. (3) The presence of the cofactor is
      sometimes essential for the polypeptide to fold. (4) Coordination of the cofactor
      prior to polypeptide folding can dramatically accelerate formation of the
      functional protein.

PMID- 11955049
TI  - Development of novel Lewis acid catalysts for selective organic reactions in
      aqueous media.
AB  - New types of Lewis acids as water-compatible catalysts have been developed.
      Various metal salts were found to work as Lewis acid catalysts in aqueous media,
      and catalytic asymmetric aldol reactions in such media have been attained.
      Furthermore, Lewis acid-surfactant combined catalysts, which can be used for
      reactions in water without using any organic cosolvents, have been also
      developed. These investigations will contribute to reducing the use of harmful
      organic solvents and to develop efficient catalytic systems which cannot be
      realized in conventional organic solvents.

PMID- 11955050
TI  - Carbon-carbon bond formation involving reactions of alkynes with group 9 metals
      (Ir, Rh, Co): preparation of conjugated olefins.
AB  - Stable alkynyl complexes of iridium(III) (L(n)Ir-triple bond-R) that are prepared
      from the reactions of terminal alkynes readily undergo the intramolecular C-C
      bond-forming reactions between the alkynyl and adjacent hydrocarbyl ligands to
      yield conjugated olefins. These reactions are initiated by electrophiles (H(+),
      Me(+)) that attack the beta carbon of the alkynyl ligand to increase the
      electrophilicity of the alpha carbon of the alkynyl ligand. The C-C bond is then
      formed between the alpha carbons of the alkynyl and adjacent hydrocarbyl ligands.

PMID- 11955051
TI  - Heteroatom-directed aromatic lithiation: a versatile route to the synthesis of
      organochalcogen (Se, Te) compounds.
AB  - Chiral and achiral organochalcogen compounds bearing a heteroatom in close
      proximity are easily accessible via the directed aromatic lithiation route. The
      lithium chalcogenolates prepared by the insertion of selenium or tellurium into
      the C-Li bond are used to synthesize various chalcogen compounds such as Se/Te, N
      donor ligands, dichalcogenides, monomeric metal chalcogenolates, and macrocycles.
      The differences in the stability and reactivity of the organochalcogen compounds
      derived from various substrates are described in terms of electronic and
      stereochemical properties of donor atoms.

PMID- 11955053
TI  - Intermolecular electron transfer reactivity determined from cross-rate studies.
AB  - Electron-transfer cross-reactions between neutral molecules and their radical
      cations spanning a wide range of structural type and intrinsic reactivity have
      been analyzed using classical Marcus theory. The principal factor found to govern
      intrinsic reactivity is the inner-shell bond reorganization energy. The HOMO-LUMO
      overlap of alkyl groups on reacting molecules is generally sufficient to provide
      facile electron transfer; however, a significant steric effect on this overlap is
      observed for hydrazines with alkyl groups larger than methyl.

PMID- 11955052
TI  - Understanding nature's strategies for enzyme-catalyzed racemization and
      epimerization.
AB  - Epimerases and racemases are enzymes that catalyze the inversion of
      stereochemistry in biological molecules. In this article, three distinct examples
      are used to illustrate the wide range of chemical strategies employed during
      catalysis, and the diverse set of ancestors from which these enzymes have
      evolved. Glutamate racemase is an example of an enzyme that operates at an
      "activated" stereocenter (bearing a relatively acidic proton) and employs a
      nonstereospecific deprotonation/reprotonation mechanism. UDP-N-Acetylglucosamine
      2-epimerase acts at an "unactivated" stereocenter and uses a mechanism involving
      a nonstereospecific elimination/addition of UDP. L-Ribulose phosphate 4-epimerase
      also acts at an unactivated stereocenter and uses a nonstereospecific
      retroaldol/aldol mechanism.

PMID- 11955054
TI  - Direct identification of a G protein ubiquitination site by mass spectrometry.
AB  - Covalent attachment of ubiquitin is well-known to target proteins for
      degradation. Here, mass spectrometry was used to identify the site of
      ubiquitination in Gpa1, the G protein alpha subunit in yeast Saccharomyces
      cerevisiae. The modified residue is located at Lys165 within the alpha-helical
      domain of Galpha, a region of unknown function. Substitution of Lys165 with Arg
      (Gpa1(K165R)) results in a substantial decrease in ubiquitination. In addition,
      yeast expressing the Gpa1(K165R) mutant are moderately resistant to pheromone in
      growth inhibition assays-a phenotype consistent with enhanced Galpha signaling
      activity. These findings indicate that the alpha-helical domain may serve to
      regulate the turnover of Gpa1.

PMID- 11955055
TI  - Mechanistic studies of a retaining alpha-galactosyltransferase from Neisseria
      meningitidis.
AB  - Lipopolysaccharyl alpha-galactosyltransferase from Neisseria meningitidis
      catalyzes the transfer of a galactosyl moiety from the activated donor UDP-Gal to
      glycoconjugates to yield an elongated saccharide product with net retention of
      anomeric configuration relative to the donor substrate. Through kinetic analyses
      in which the concentrations of both substrates are independently varied and
      through inhibition studies with dead-end analogues of both substrates and with
      the oligosaccharide product, we have demonstrated that this enzyme follows an
      ordered bi-bi kinetic mechanism. Various aspects of the chemical mechanism
      including the possible formation of a covalent glycosyl-enzyme intermediate were
      also probed using an assortment of strategies. While the results of these
      investigations were unable to clearly delineate the chemical mechanism of this
      enzyme, they provide important insights into the catalytic machinery surrounding
      the events involved in catalysis.

PMID- 11955056
TI  - Agonist-specific, high-affinity binding epitopes are contributed by an arginine
      in the N-terminus of the human oxytocin receptor.
AB  - The effects of the peptide hormone oxytocin (OT) are mediated by the oxytocin
      receptor, which is a member of the G-protein-coupled receptor family. Defining
      differences between the binding of agonists and antagonists to the OTR, at the
      molecular level, is of fundamental importance to understanding OTR activation and
      to rational drug design. Previous reports have indicated that the N-terminus of
      the OTR is required for OT binding. The aim of this study was to identify which
      individual residues within the N-terminal domain of the human OTR provided these
      OT binding epitopes. A series of truncated OTRs and mutant receptor constructs
      with systematic alanine substitution were characterized with respect to their
      pharmacological profile and intracellular signaling capability. Although a number
      of residues within the OTR will be required for optimal OT-OTR interaction, our
      data establish that Arg(34) within the N-terminal domain contributes to high
      affinity OT binding. Removal of Arg(34) by truncation or substitution resulted in
      a 2000-fold decrease in OT affinity. In addition, we show that the arginyl at
      this locus is required for high-affinity binding of agonists in general. However,
      the importance of Arg(34) is restricted to agonist interaction with the OTR, as
      it was not required for binding peptide antagonist or non-peptide antagonist. It
      is noteworthy that the corresponding Arg in the related rat V(1a) vasopressin
      receptor is also required for high-affinity agonist binding. This study defines,
      at the molecular level, the role of the N-terminus of the OTR in high-affinity
      agonist binding and identifies a key residue for this function.

PMID- 11955057
TI  - Characterization of the protrimer intermediate in the folding pathway of the
      interdigitated beta-helix tailspike protein.
AB  - P22 tailspike is a homotrimeric, thermostable adhesin that recognizes the O
      antigen lipopolysaccharide of Salmonella typhimurium. The 70 kDa subunits include
      long beta-helix domains. After residue 540, the polypeptide chains change their
      path and wrap around one another, with extensive interchain contacts. Formation
      of this interdigitated domain intimately couples the chain folding and assembly
      mechanisms. The earliest detectable trimeric intermediate in the tailspike
      folding and assembly pathway is the protrimer, suspected to be a precursor of the
      native trimer structure. We have directly analyzed the kinetics of in vitro
      protrimer formation and disappearance for wild type and mutant tailspike
      proteins. The results confirm that the protrimer intermediate is an on-pathway
      intermediate for tailspike folding. Protrimer was originally resolved during
      tailspike folding because its migration through nondenaturing polyacrylamide gels
      was significantly retarded with respect to the migration of the native tailspike
      trimer. By comparing protein mobility versus acrylamide concentration, we find
      that the retarded mobility of the protrimer is due exclusively to a larger
      overall size than the native trimer, rather than an altered net surface charge.
      Experiments with mutant tailspike proteins indicate that the conformation
      difference between protrimer and native tailspike trimer is localized toward the
      C-termini of the tailspike polypeptide chains. These results suggest that the
      transformation of the protrimer to the native tailspike trimer represents the C
      terminal interdigitation of the three polypeptide chains. This late step may
      confer the detergent-resistance, protease-resistance, and thermostability of the
      native trimer.

PMID- 11955058
TI  - A 15N NMR mobility study on the dicalcium P43M calbindin D9k and its mono-La3+
      substituted form.
AB  - Calbindin D(9k) is a dicalcium binding protein consisting of two helix-loop-helix
      EF-hand motifs joined together by a flexible linker region where one metal ion
      can bind to each of the two loops. A proline residue at position 43 in the linker
      region displays cis-trans isomerism in the wild-type (WT) protein. Such isomerism
      appeared to be removed by substituting the proline with a glycine or a methionine
      in the P43G or P43M mutant. We have extended the available mobility studies on
      the P43M mutant through amide (15)N R(1), R(2), and R(1)(rho)() measurements.
      This has revealed unexpected conformational equilibria on the millisecond time
      scale involving residues 38, 42-44, and 46 in the linker region and residues 18
      and 19 in calcium binding site I with similar energy barriers. These data are
      discussed in comparison with those available for the WT, as well as the apo-,
      mono-, and disubstituted P43G mutant. Quantification of water-amide proton
      exchange rates using saturation transfer and qualitative application of (15)N
      (CLEANEX-PM)-FHSQC shows the values are in agreement with high mobility for the
      above-mentioned residues. Cross correlation between N-H dipole-dipole relaxation
      and (15)N CSA relaxation indicates that some of these mobility differences may
      extend to the sub-nanosecond time scale. Similar data were also obtained for the
      derivative where the calcium ion in the C-terminal loop was replaced with
      lanthanum. The results presented here show that, contrary to expectations, there
      are significant differences in dynamics between the dicalcium state of P43G and
      P43M and that these differences are not confined to the flexible linker region
      containing the point mutation. They also demonstrate that substitution of a
      lanthanide ion for calcium, which is a common procedure, does not significantly
      alter the mobility of the native protein.

PMID- 11955059
TI  - Solution structure of a monoheme ferrocytochrome c from Shewanella putrefaciens
      and structural analysis of sequence-similar proteins: functional implications.
AB  - Within the frame of the characterization of the structure and function of
      cytochromes c, an 81-amino acid cytochrome c was identified in the genome of
      Shewanella putrefaciens. Because of the scarce information about bacterial
      cytochromes of this type and the large variability in sequences and possibly
      function, we decided to proceed to its structural characterization. This protein
      was expressed in Escherichia coli and purified. The oxidized species is largely
      high spin, with a detached methionine, whereas the reduced species has the
      classical His/Met axial ligation to iron. The NMR solution structure of the
      reduced form was determined on a (15)N-labeled sample, for which 99% of all non
      proline backbone (1)H and (15)N resonances have been assigned. One thousand three
      hundred two meaningful NOEs, out of 1775 NOEs, together with 66 dihedral angles
      provide a structure with rmsd values from the mean of 0.50 and 0.96 A for
      backbone and all heavy atoms, respectively. A search of gene banks allowed us to
      locate 10 different cytochromes c, the sequences of which are more than 30%
      identical to that of the S. putrefacienscytochrome. For two of them, the
      structures are known. The structures of the others have been modeled by using the
      available templates and internally validated. Structural similarities in terms of
      surface properties account for their biophysical features and provide hints about
      the function.

PMID- 11955060
TI  - Structural investigation of the binding of a herpesviral protein to the SH3
      domain of tyrosine kinase Lck.
AB  - Herpesvirus saimiri codes for a tyrosine kinase interacting protein (Tip) that
      interacts with both the SH3 domain and the kinase domain of the T-cell-specific
      tyrosine kinase Lck via two separate motifs. The activation of Lck by Tip is
      considered as a key event in the transformation of human T-lymphocytes during
      herpesviral infection. We investigated the interaction of proline-rich Tip
      peptides with the LckSH3 domain starting with the structural characterization of
      the unbound interaction partners. The solution structure of the LckSH3 was
      determined by heteronuclear multidimensional nuclear magnetic resonance (NMR)
      spectroscopy using 44 residual dipolar couplings in addition to the conventional
      experimental restraints. Circular dichroism spectroscopy proved that the
      polyproline helix of Tip is already formed prior to SH3 binding and is
      conformationally stable. NMR titration experiments point out three major regions
      of the Tip-Lck interaction comprising the RT loop, the n-src loop, and a helical
      turn preceding the last strand of the beta-sheet. Further changes of the chemical
      shifts were observed for the N- and C-terminal beta-strands of the SH3 domain,
      indicating additional contacts outside the proline-rich segment or subtle
      structural rearrangements transmitted from the binding site of the proline helix.
      Fluorescence spectroscopy shows that Tip binds to the SH3 domains of several Src
      kinases (Lck, Hck, Lyn, Src, Fyn, Yes), exhibiting the highest affinities for
      Lyn, Hck, and Lck.

PMID- 11955061
TI  - Induced formation of a DNA bulge structure by a molecular wedge ligand
      postactivated neocarzinostatin chromophore.
AB  - Our previous structure elucidation of the complexes of DNA and postactivated
      neocarzinostatin chromophore (NCS-chrom) compounds revealed two distinctly
      different binding modes of this antitumor molecule. A thorough understanding of
      these results will provide the molecular basis for the binding and DNA chain
      cleavage properties of NCS-chrom. NCSi-gb is one of the postactivated mimics of
      NCS-chrom which is formed under thiol-free conditions and is able to bind to DNA.
      This report describes the structure refinement of the NCSi-gb-bulge-DNA complex
      [Stassinopoulos, A., Jie, J., Gao, X., and Goldberg, I. H. (1996) Science 272,
      1943-1946] and the NMR characterization of the free bulge-DNA and free NCSi-gb.
      These results reveal that the formation of the complex involves conformational
      changes in both the DNA and the ligand molecule. Of mechanistic importance for
      the NCS-chrom-DNA interaction, the two ring systems of the drug are brought
      closer to each other in the complex. This conformation correlates well with the
      previously observed marked enhancement of the formation of a DNA bulge cleaving
      species in the presence of bulge-DNA sequences, due to the promotion of the
      intramolecular radical quenching of the activated NCS-chrom. Interestingly, the
      binding of NCSi-gb promotes the formation of a bulge binding pocket; this was not
      found in the unbound DNA. NCS-chrom is unique among the enediyne antibiotics in
      its ability to undergo two different mechanisms of activation to form two
      different DNA binding and cleaving species. The two corresponding DNA complexes
      are compared. One, the bulge-DNA binder NCSi-gb, involves the major groove, and
      the second, the duplex binder NCSi-glu which is generated by glutathione-induced
      activation, involves the minor groove. Since the two NCS-chrom-related ligand
      molecules contain some common chemical structural elements, such as the
      carbohydrate ring, the striking differences in their DNA recognition and chain
      cleavage specificity provide insights into the fundamental principles of DNA
      recognition and ligand design.

PMID- 11955062
TI  - Role of T7 RNA polymerase His784 in start site selection and initial
      transcription.
AB  - The role of steric constraints vs sequence preference in start site selection by
      T7 RNA polymerase was investigated by using a series of synthetic promoters in
      which the preferred template strand 'CC' initiation sequence was moved away from
      its normal position relative to the -17 to -6 element of the T7 promoter. It was
      found that the CC sequence directs efficient initiation if placed 1 or 2 nt
      downstream of its normal position, but not if placed upstream, or more than 2 nt
      downstream, of +1. Mutagenesis revealed that part of the bias to initiate with
      GTP is due to an interaction between histidine 784 and the 2-amino group of a
      guanosine bound in the initiating triphosphate position. This interaction is also
      important for holding short transcripts within the transcription complex during
      initial transcription.

PMID- 11955063
TI  - Insights into the molecular mechanism of inhibition and drug resistance for HIV-1
      RT with carbovir triphosphate.
AB  - Abacavir (1592U89, or Ziagen) is a powerful and selective inhibitor of HIV-1
      viral replication that has been approved by the FDA for treatment of acquired
      immunodeficiency syndrome. Abacavir is metabolized to the active compound
      carbovir triphosphate (CBVTP). This compound is a guanosine analogue containing a
      2',3'-unsaturation in its planar carbocyclic deoxyribose ring that acts on HIV-1
      reverse transcriptase (RT(WT)) as a molecular target, resulting in chain
      termination of DNA synthesis. A single amino acid change from methionine 184 to
      valine in HIV-1 RT (RT(M184V)) has been observed clinically in response to
      abacavir treatment. The ability of the natural substrate, dGTP, or CBVTP to be
      utilized during DNA- and RNA-directed polymerization by RT(WT) and RT(M184V) was
      defined by pre-steady-state kinetic parameters. In the case of RT(WT), CBVTP was
      found to be a surprisingly poor substrate relative to dGTP. In both DNA- and RNA
      directed polymerization, a decrease in the efficiency of CBVTP utilization with
      respect to dGTP was found with RT(M184V), suggesting that this mutation confers
      resistance at the level of CBVMP incorporation. The relatively low incorporation
      efficiency for RT(WT) was unanticipated considering earlier studies showing that
      the triphosphate form of a thymidine nucleoside analogue containing a planar
      2',3'-unsaturated ribose ring, D4TTP, was incorporated with high efficiency
      relative to the natural substrate, dTTP. The difference may be related to the
      isosteric replacement of oxygen in the deoxyribose ring with carbon. This
      hypothesis was tested by synthesizing and evaluating D4GTP (the planar 2',3'
      unsaturated deoxyribose guanosine analogue that is complementary to D4TTP). In
      contrast to CBVTP, D4GTP was found to be an excellent substrate for RT(WT) and no
      resistance was conferred by the M184V mutation, thus providing novel insight into
      structure-activity relationships for nucleoside-based inhibitors. In this work,
      we illustrate how an understanding of the molecular mechanism of inhibition and
      drug resistance led to the discovery of a novel prodrug of D4G. This compound
      shows promise as a potent antiviral especially with the drug resistant M184V HIV
      1 RT that is so often encountered in a clinical setting.

PMID- 11955064
TI  - Electron crystallographic study of photosystem II of the cyanobacterium
      Synechococcus elongatus.
AB  - The determination of the structure of PSII at high resolution is required in
      order to fully understand its reaction mechanisms. Two-dimensional crystals of
      purified highly active Synechococcus elongatus PSII dimers were obtained by in
      vitro reconstitution. Images of these crystals were recorded by electron cryo
      microscopy, and their analysis revealed they belong to the two-sided plane group
      p22(1)2(1), with unit cell parameters a = 121 A, b = 333 A, and alpha = 90
      degrees. From these crystals, a projection map was calculated to a resolution of
      approximately 16 A. The reliability of this projection map is confirmed by its
      close agreement with the recently presented three-dimensional model of the same
      complex obtained by X-ray crystallography. Comparison of the projection map of
      the Synechococcus elongatus PSII complex with data obtained by electron
      crystallography of the spinach PSII core dimer reveals a similar organization of
      the main transmembrane subunits. However, some differences in density
      distribution between the cyanobacterial and higher plant PSII complexes exist,
      especially in the outer region of the complex between CP43 and cytochrome b(559)
      and adjacent to the B-helix of the D1 protein. These differences are discussed in
      terms of the number and organization of some of the PSII low molecular weight
      subunits.

PMID- 11955065
TI  - Role of hydrogen bonds in the reaction mechanism of chalcone isomerase.
AB  - In flavonoid, isoflavonoid, and anthocyanin biosynthesis, chalcone isomerase
      (CHI) catalyzes the intramolecular cyclization of chalcones into (S)-flavanones
      with a second-order rate constant that approaches the diffusion-controlled limit.
      The three-dimensional structures of alfalfa CHI complexed with different
      flavanones indicate that two sets of hydrogen bonds may possess critical roles in
      catalysis. The first set of interactions includes two conserved amino acids
      (Thr48 and Tyr106) that mediate a hydrogen bond network with two active site
      water molecules. The second set of hydrogen bonds occurs between the flavanone 7
      hydroxyl group and two active site residues (Asn113 and Thr190). Comparison of
      the steady-state kinetic parameters of wild-type and mutant CHIs demonstrates
      that efficient cyclization of various chalcones into their respective flavanones
      requires both sets of contacts. For example, the T48A, T48S, Y106F, N113A, and
      T190A mutants exhibit 1550-, 3-, 30-, 7-, and 6-fold reductions in k(cat) and 2-3
      fold changes in K(m) with 4,2',4'-trihydroxychalcone as a substrate. Kinetic
      comparisons of the pH-dependence of the reactions catalyzed by wild-type and
      mutant enzymes indicate that the active site hydrogen bonds contributed by these
      four residues do not significantly alter the pK(a) of the intramolecular
      cyclization reaction. Determinations of solvent kinetic isotope and solvent
      viscosity effects for wild-type and mutant enzymes reveal a change from a
      diffusion-controlled reaction to one limited by chemistry in the T48A and Y106F
      mutants. The X-ray crystal structures of the T48A and Y106F mutants support the
      assertion that the observed kinetic effects result from the loss of key hydrogen
      bonds at the CHI active site. Our results are consistent with a reaction
      mechanism for CHI in which Thr48 polarizes the ketone of the substrate and Tyr106
      stabilizes a key catalytic water molecule. Hydrogen bonds contributed by Asn113
      and Thr190 provide additional stabilization in the transition state. Conservation
      of these residues in CHIs from other plant species implies a common reaction
      mechanism for enzyme-catalyzed flavanone formation in all plants.

PMID- 11955066
TI  - Quantifying the energetics of cooperativity in a ternary protein complex.
AB  - The formation of complexes involving more than two proteins is critical for many
      cellular processes, including signal transduction, transcriptional control, and
      cytoskeleton remodeling. Energetically, these interactions cannot always be
      described simply by the additive effects of the individual binary reactions that
      make up the overall complex. This is due, in large part, to cooperative
      interactions between separate protein domains. Thus, a full understanding of
      multiprotein complexes requires the quantitative analysis of cooperativity. We
      have used surface plasmon resonance techniques and mathematical modeling to
      describe the energetics of cooperativity in a trimolecular protein complex. As a
      model system for quantifying cooperativity, we studied the ternary complex formed
      by the simultaneous interaction of a superantigen with major histocompatibility
      complex and T cell receptor, for which a structural model is available. This
      system exhibits positive and negative cooperativity, as well as augmentation of
      the temperature dependence of binding kinetics upon the cooperative interaction
      of individual protein components in the complex. Our experimental and theoretical
      analysis may be applicable to other systems involving cooperativity.

PMID- 11955067
TI  - X-ray crystal structure of Escherichia coli taurine/alpha-ketoglutarate
      dioxygenase complexed to ferrous iron and substrates.
AB  - Taurine/alpha-ketoglutarate dioxygenase (TauD), a non-heme Fe(II) oxygenase,
      catalyses the conversion of taurine (2-aminoethanesulfonate) to sulfite and
      aminoacetaldehyde concurrent with the conversion of alpha-ketoglutarate (alphaKG)
      to succinate and CO(2). The enzyme allows Escherichia coli to use taurine, widely
      available in the environment, as an alternative sulfur source. Here we describe
      the X-ray crystal structure of TauD complexed to Fe(II) and both substrates,
      alphaKG and taurine. The tertiary structure and fold of TauD are similar to those
      observed in other enzymes from the broad family of Fe(II)/alphaKG-dependent
      oxygenases, with closest structural similarity to clavaminate synthase. Using the
      TauD coordinates, a model was determined for the closely related enzyme 2,4
      dichlorophenoxyacetate/alphaKG dioxygenase (TfdA), supporting predictions derived
      from site-directed mutagenesis and other studies of that biodegradative protein.
      The TauD structure and TfdA model define the metal ligands and the positions of
      nearby aromatic residues that undergo post-translational modifications involving
      self-hydroxylation reactions. The substrate binding residues of TauD were
      identified and those of TfdA predicted. These results, along with sequence
      alignment information, reveal how TauD selects a tetrahedral substrate anion in
      preference to the planar carboxylate selected by TfdA, providing insight into the
      mechanism of enzyme catalysis.

PMID- 11955068
TI  - Metabolic engineering of a methylmalonyl-CoA mutase-epimerase pathway for complex
      polyketide biosynthesis in Escherichia coli.
AB  - A barrier to heterologous production of complex polyketides in Escherichia coli
      is the lack of (2S)-methylmalonyl-CoA, a common extender substrate for the
      biosynthesis of complex polyketides by modular polyketide synthases. One
      biosynthetic route to (2S)-methylmalonyl-CoA involves the sequential actions of
      two enzymes, methylmalonyl-CoA mutase and methylmalonyl-CoA epimerase, which
      convert succinyl-CoA to (2R)- and then to (2S)-methylmalonyl-CoA. As reported
      [McKie, N., et al. (1990) Biochem. J. 269, 293-298; Haller, T., et al. (2000)
      Biochemistry 39, 4622-4629], when genes encoding coenzyme B(12)-dependent
      methylmalonyl-CoA mutases were expressed in E. coli, the inactive apo-enzyme was
      produced. However, when cells harboring the mutase genes from Propionibacterium
      shermanii or E. coli were treated with the B12 precursor hydroxocobalamin, active
      holo-enzyme was isolated, and (2R)-methylmalonyl-CoA represented approximately
      10% of the intracellular CoA pool. When the E. coli BAP1 cell line [Pfeifer, B.
      A., et al. (2001) Science 291, 1790-1792] harboring plasmids that expressed P.
      shermanii methylmalonyl-CoA mutase, Streptomyces coelicolor methylmalonyl-CoA
      epimerase, and the polyketide synthase DEBS (6-deoxyerythronolide B synthase) was
      fed propionate and hydroxocobalamin, the polyketide 6-deoxyerythronolide B (6
      dEB) was produced. Isotopic labeling studies using [(13)C]propionate showed that
      the starter unit for polyketide synthesis was derived exclusively from exogenous
      propionate, while the extender units stemmed from methylmalonyl-CoA via the
      mutase-epimerase pathway. Thus, the introduction of an engineered mutase
      epimerase pathway in E. coli enabled the uncoupling of carbon sources used to
      produce starter and extender units of polyketides.

PMID- 11955069
TI  - Hemin-stimulated docking of cytochrome c to a hemin-DNA aptamer complex.
AB  - DNA aptamers were selected for their ability to bind simultaneously to the
      protein cytochrome c and to the metalloporphyrin hemin. Such aptamers each
      contained a conserved guanine-rich core, analogous to sequences shown previously
      to form a hemin-binding site when folded. The detailed study of CH6A, a deletion
      mutant of one clone, indicated that in the presence of hemin the guanine-rich
      core of the aptamer folded to form a guanine quadruplex. Both hemin and potassium
      ions were required for this folding. The binding of fully oxidized cytochrome c
      to this DNA-hemin complex resulted in an absorbance difference spectrum in the
      Soret region, which could be used as an indicator of binding behavior. It was
      found that cytochrome c bound more tightly to the folded CH6A DNA-hemin complex
      than to the folded CH6A DNA alone. A single hemin molecule and a single
      cytochrome c bound to each molecule of folded CH6A. Footprinting experiments
      showed the binding site of the cytochrome c to be a partial duplex element of the
      aptamer, immediately flanking its guanine-rich hemin-binding site. The order of
      addition of hemin and cytochrome c appeared not to affect either the formation
      rate or the structure of the final ternary complex. The ternary complex
      represents the docking of a nucleic acid-heme complex to cytochrome c (a protein
      heme complex). Future experiments will focus on investigating the optimal
      electron-transfer path between the two iron centers through intervening protein
      and DNA.

PMID- 11955070
TI  - Structure of the pyruvate dehydrogenase multienzyme complex E1 component from
      Escherichia coli at 1.85 A resolution.
AB  - The crystal structure of the recombinant thiamin diphosphate-dependent E1
      component from the Escherichia coli pyruvate dehydrogenase multienzyme complex
      (PDHc) has been determined at a resolution of 1.85 A. The E. coli PDHc E1
      component E1p is a homodimeric enzyme and crystallizes with an intact dimer in an
      asymmetric unit. Each E1p subunit consists of three domains: N-terminal, middle,
      and C-terminal, with all having alpha/beta folds. The functional dimer contains
      two catalytic centers located at the interface between subunits. The ThDP
      cofactors are bound in the "V" conformation in clefts between the two subunits
      (binding involves the N-terminal and middle domains), and there is a common ThDP
      binding fold. The cofactors are completely buried, as only the C2 atoms are
      accessible from solution through the active site clefts. Significant structural
      differences are observed between individual domains of E1p relative to
      heterotetrameric multienzyme complex E1 components operating on branched chain
      substrates. These differences may be responsible for reported alternative E1p
      binding modes to E2 components within the respective complexes. This paper
      represents the first structural example of a functional pyruvate dehydrogenase
      E1p component from any species. It also provides the first representative example
      for the entire family of homodimeric (alpha2) E1 multienzyme complex components,
      and should serve as a model for this class of enzymes.

PMID- 11955071
TI  - Receptor type I and type II binding regions and the peptidyl-prolyl isomerase
      site of cyclophilin B are required for enhancement of T-lymphocyte adhesion to
      fibronectin.
AB  - Cyclophilin B (CyPB), a cyclosporin A (CsA) binding protein, interacts with two
      types of binding sites at the surface of T-lymphocytes. The type I sites
      correspond to functional receptors involved in endocytosis and the type II sites
      to sulfated glycosaminoglycans (GAGs). Mutational analysis of CyPB has revealed
      that W128, which is part of the CsA-binding pocket, is implicated in the binding
      to the functional type I receptors and that two amino acid clusters located in
      the N-terminus ensure the binding to GAGs. The peptidyl-prolyl isomerase activity
      of CyPB is not required for receptor binding. We have recently demonstrated that
      CyPB enhances adhesion of peripheral blood T-lymphocytes to fibronectin, a
      component of the extracellular matrix. We intended to identify additional amino
      acids involved in the binding of CyPB to its functional type I receptor and to
      determine regions responsible for the stimulation of peripheral blood T
      lymphocyte adhesion. We determined that residues R76, G77, K132, D155, and D158
      of the calcineurin (CN) interacting region were implicated in the recognition of
      type I receptor but not of GAGs. We also found that two different changes in the
      N-terminal extension that abated binding to GAGs prevented adhesion of peripheral
      blood T-lymphocytes to coated CyPB, whereas abbrogation of the PPIase activity
      had no effect. On the other hand, the adhesion of peripheral blood T-lymphocytes
      to coated fibronectin was not stimulated by CyPB mutants devoid of either type I
      receptor or GAGs binding activity or by mutants of the PPIase site. Altogether,
      the results demonstrate that different regions of CyPB are involved in peripheral
      blood T-lymphocyte activation and imply a novel important physiological function
      for peptidyl-prolyl isomerase activity.

PMID- 11955072
TI  - Analysis of NSF mutants reveals residues involved in SNAP binding and ATPase
      stimulation.
AB  - N-Ethylmaleimide-sensitive fusion protein (NSF) and its yeast orthologue, Sec18,
      are cytoplasmic AAA(+) ATPases required for most intracellular membrane fusion
      events. The primary function of NSF is thought to be the disassembly of cis-SNARE
      complexes, thus allowing trans-SNARE complex formation and subsequent membrane
      fusion. The importance of NSF/Sec18 in intracellular membrane traffic in vivo is
      highlighted by the inhibition of neurotransmission in Drosophila comatose (NSF)
      mutants and of constitutive secretion in yeast sec18 mutants. However, the
      underlying biochemical defects in these mutant proteins are largely unknown.
      Here, we identify the sec18-1 mutation as a G89D substitution in the N domain of
      Sec18p. This mutation results in an inhibition of the mutant protein's ability to
      bind to Sec17p (yeast alpha-SNAP). In contrast, engineering the comatose(st53)()
      mutation (S483L) into mammalian NSF (S491L) has no effect on alpha-SNAP binding.
      Instead, the stimulation of ATPase activity by alpha-SNAP required for wild-type
      NSF to disassemble SNARE complexes does not occur in the mutant NSF(st53)
      protein. This biochemical phenotype predicts a dominant negative effect, which
      was confirmed by engineering the st53 mutation into Sec18 (A505L), resulting in a
      dominant lethal phenotype in vivo. These findings suggest a biochemical basis for
      the block in membrane fusion observed in the mutant organisms. Furthermore, the
      mutants characterized here define key residues involved in two essential, but
      mechanistically distinct, biochemical functions of NSF: SNAP binding and SNAP
      dependent ATPase stimulation.

PMID- 11955073
TI  - A mutational analysis of the PD...D/EXK motif suggests that McrC harbors the
      catalytic center for DNA cleavage by the GTP-dependent restriction enzyme McrBC
      from Escherichia coli.
AB  - McrBC is a unique restriction enzyme which binds specifically to the bipartite
      recognition sequence R(m)CN( approximately )(30)(-)( approximately )(2000)R(m)C
      and in the presence of GTP translocates the DNA and cleaves both strands at
      multiple positions within the two R(m)C "half-sites". It is known that McrBC is
      composed of two subunits: McrB which binds and hydrolyzes GTP and specifically
      interacts with DNA and McrC whose function is not clear but which has been
      suspected to harbor the catalytic center for DNA cleavage. A multiple-sequence
      alignment of the amino acid sequence of Escherichia coli McrC and of six
      presumably homologous open reading frames from various bacterial species shows
      that a sequence motif found in many restriction enzymes, but also in other
      nucleases, the PD.D/EXK motif, is conserved among these sequences. A mutational
      analysis, in which the carboxylates (aspartic acid in McrC) of this motif were
      substituted with alanine or asparagine and lysine was substituted with alanine or
      arginine, strongly suggests that Asp244, Asp257, and Lys259 represent the
      catalytic center of E. coli McrC. Whereas the variants D244A (or -N), D257A (or 
      N), and K259A are inactive in DNA cleavage (K259R has residual DNA cleavage
      activity), they interact with McrB like wild-type McrC, as can be deduced from
      the finding that they stimulate the McrB-catalyzed GTP hydrolysis to the same
      extent as wild-type McrC. Thus, whereas McrC variants defective in DNA cleavage
      can stimulate the GTPase activity of McrB, the DNase activity of McrC is not
      supported by McrB variants defective in GTP hydrolysis.

PMID- 11955074
TI  - The GTP-dependent restriction enzyme McrBC from Escherichia coli forms high
      molecular mass complexes with DNA and produces a cleavage pattern with a
      characteristic 10-base pair repeat.
AB  - The GTP-dependent restriction enzyme McrBC consists of two polypeptides: one
      (McrB) that is responsible for GTP binding and hydrolysis as well as DNA binding
      and another (McrC) that is responsible for DNA cleavage. It recognizes two
      methylated or hemimethylated RC sites (R(m)C) at a distance of approximately 30
      to more than 2000 base pairs and cleaves the DNA close to one of the two R(m)C
      sites. This process is strictly coupled to GTP hydrolysis and involves the
      formation of high-molecular mass complexes. We show here using footprinting
      techniques, surface plasmon resonance, and scanning force microscopy experiments
      that in the absence of McrC, McrB binds to a single R(m)C site. If a second R(m)C
      site is present on the DNA, it is occupied independently by McrB. Whereas the DNA
      binding domain of McrB forms 1:1 complexes with each R(m)C site and shows a clear
      footprint on both R(m)C sites, full-length McrB forms complexes with a
      stoichiometry of at least 4:1 at each R(m)C site, resulting in a slightly more
      extended footprint. In the presence of McrC, McrB forms high-molecular mass
      complexes of unknown stoichiometry, which are considerably larger than the
      complexes formed with McrB alone. In these complexes and when GTP is present, the
      DNA is cleaved next to one of the R(m)C sites at distances differing by one to
      five helical turns, suggesting that in the McrBC-DNA complex only a few
      topologically well-defined phosphodiester bonds of the DNA are accessible for the
      nucleolytic center of McrC.

PMID- 11955075
TI  - Cell cycle specific plasmid DNA replication in the nuclear extract of
      Saccharomyces cerevisiae: modulation by replication protein A and proliferating
      cell nuclear antigen.
AB  - Plasmid DNA replication in nuclear extracts of Saccharomyces cerevisiae in vitro
      has been shown to be S-phase specific, similar to that observed in vivo. We
      report here a reconstituted in vitro system with partially purified replication
      proteins, purified replication protein A (RPA), and recombinant proliferating
      cell nuclear antigen (PCNA). Nuclear extracts from S-phase, G(1)-phase, and
      unsynchronized yeast cells were fractionated by phosphocellulose chromatography.
      Protein fraction (polymerase fraction) enriched with replication proteins,
      including DNA polymerases (alpha, delta, etc.), was isolated, which was not
      capable of in vitro replication of supercoiled plasmid DNA. However, when
      purified yeast RPA and recombinant PCNA together were added to the polymerase
      fraction obtained from S-phase synchronized cells, in vitro plasmid DNA
      replication was restored. In vitro plasmid DNA replication with polymerase
      fractions from unsynchronized and G(1)-phase cells could not be reconstituted
      upon addition of purified RPA and PCNA. RPA and PCNA isolated from various phases
      of the cell cycle complemented the S-phase polymerase pool to the same extent.
      Reconstituted systems with the S-phase polymerase pool, complemented with either
      the RPA- and PCNA-containing fraction or purified RPA and recombinant PCNA
      together, were able to produce replication intermediates (ranging in size from 50
      to 1500 bp) similar to that observed with the S-phase nuclear extract. Results
      presented here demonstrate that both RPA and PCNA are cell cycle-independent in
      their ability to stimulate in vitro plasmid DNA replication, whereas replication
      factors in the polymerase fractions are strictly S-phase dependent.

PMID- 11955076
TI  - Hydrolysis of the 5'-p-nitrophenyl ester of TMP by the proofreading exonuclease
      (epsilon) subunit of Escherichia coli DNA polymerase III.
AB  - The core of DNA polymerase III, the replicative polymerase in Escherichia coli,
      consists of three subunits (alpha, epsilon, and theta). The epsilon subunit is
      the 3'-5' proofreading exonuclease that associates with the polymerase (alpha)
      through its C-terminal region and theta through a 185-residue N-terminal domain
      (epsilon 186). A spectrophotometric assay for measurement of epsilon activity is
      described. Proteins epsilon and epsilon 186 and the epsilon 186.theta complex
      catalyzed the hydrolysis of the 5'-p-nitrophenyl ester of TMP (pNP-TMP) with
      similar values of k(cat) and K(M), confirming that the N-terminal domain of
      epsilon bears the exonuclease active site, and showing that association with
      theta has little direct effect on the chemistry occurring at the active site of
      epsilon. On the other hand, formation of the complex with theta stabilized
      epsilon 186 by approximately 14 degrees C against thermal inactivation. For
      epsilon 186, k(cat) = 293 min(-)(1) and K(M) = 1.08 mM at pH 8.00 and 25 degrees
      C, with a Mn(2+) concentration of 1 mM. Hydrolysis of pNP-TMP by epsilon 186
      depended absolutely on divalent metal ions, and was inhibited by the product TMP.
      Dependencies on Mn(2+) and Mg(2+) concentrations were examined, giving a K(Mn) of
      0.31 mM and a k(cat) of 334 min(-1) for Mn(2+) and a K(Mg) of 6.9 mM and a k(cat)
      of 19.9 min(-1) for Mg(2+). Inhibition by TMP was formally competitive [K(i) =
      4.3 microM (with a Mn(2+) concentration of 1 mM)]. The pH dependence of pNP-TMP
      hydrolysis by epsilon 186, in the pH range of 6.5-9.0, was found to be simple.
      K(M) was essentially invariant between pH 6.5 and 8.5, while k(cat) depended on
      titration of a single group with a pK(a) of 7.7, approaching limiting values of
      50 min(-1) at pH <6.5 and 400 min(-1) at pH >9.0. These data are used in
      conjunction with crystal structures of the complex of epsilon 186 with TMP and
      two Mn(II) ions bound at the active site to develop insights into the mechanisms
      of pNP-TMP hydrolysis by epsilon at high and low pH values.

PMID- 11955077
TI  - Affinities of packaging domain loops in HIV-1 RNA for the nucleocapsid protein.
AB  - To design anti-nucleocapsid drugs, it is useful to know the affinities the
      protein has for its natural substrates under physiological conditions.
      Dissociation equilibrium constants are reported for seven RNA stem-loops bound to
      the mature HIV-1 nucleocapsid protein, NCp7. The loops include SL1, SL2, SL3, and
      SL4 from the major packaging domain of genomic RNA. The binding assay is based on
      quenching the fluorescence of tryptophan-37 in the protein by G residues in the
      single-stranded loops. Tightly bound RNA molecules quench nearly all the
      fluorescence of freshly purified NCp7 in 0.2 M NaCl. In contrast, when the GGAG
      tetraloop of tight-binding SL3 is replaced with UUCG or GAUA, quenching is almost
      nil, indicating very low affinity. Interpreting fluorescence titrations in terms
      of a rapidly equilibrating 1:1 complex explains nearly all of the experimental
      variance for the loops. Analyzed in this way, the highest affinities are for
      20mer SL3 and 19mer SL2 hairpin constructs (K(d) = 28 +/- 3 and 23 +/- 2 nM,
      respectively). The 20mer stem-UUCG-loop and GAUA-loop constructs have <0.5% of
      the affinity for NCp7 relative to SL3. Affinities relative to SL3 for the other
      stem-loops are the following: 10% for a 16mer construct to model SL4, 30% for a
      27mer model of the 9-residue apical loop of SL1, and 20% for a 23mer model of a 1
      x 3 asymmetric internal loop in SL1. A 154mer construct that includes all four
      stem-loops binds tightly to NCp7, with the equivalent of three NCp7 molecules
      bound with high affinity per RNA; it is also possible that two strong sites and
      several weaker ones combine to give the appearance of three strong sites.

PMID- 11955078
TI  - DNA modification by 4-aza-3-ene-1,6-diynes: DNA cleavage, pH-dependent cytosine
      specific interactions, and cancer cell cytotoxicity.
AB  - The (Z)-hex-1,5-diyne-3-ene reactive core common to the enediyne antitumor
      antibiotics undergoes a Bergman cyclization after proper activation to afford
      reactive diradical intermediates that are responsible for initiating DNA
      cleavage. Direct modification of the enediyne core has been proposed as a method
      to permit cancer cell-specific triggering of the diradical-generating
      cyclization. For example, 3-aza-3-ene-1,5-diynes undergo an aza-Bergman
      cyclization to afford the fleeting 2,5-didehydropyridine diradicals. While
      protonation of these aza-enediynes can afford products of diradical trapping, the
      hydrolytic instability of the 3-aza-3-ene-1,5-diyne moiety prevents its use in pH
      triggered DNA cleaving anticancer agents. Recently, more hydrolytically stable
      systems incorporating the 4-aza-3-ene-1,6-diyne moiety were developed. We report
      here studies of the 4-aza-3-ene-1,6-diyne-containing benzimidazolium salt AZB002
      [1-methyl-2-(phenylethynyl)-3-(3-phenylprop-2-ynyl)-3H-benzimidazolium
      tetrafluoroborate] and two structurally related heterocycles that lack the aza
      enediyne functionality, AZB016 [1,3-dimethyl-2-(phenylethynyl)-3H-benzimidazolium
      triflate] and AZB004 [3-methyl-2-(phenylethynyl)benzothiazolium triflate]. The
      interaction of these compounds with supercoiled DNA, a double-stranded DNA
      fragment, and a short DNA duplex oligonucleotide was investigated. There are
      three distinct DNA interactions exhibited by AZB002: a frank strand scission
      leading to the relaxation of supercoiled DNA and formation of at least two
      different DNA adducts, one of which leads to cytosine-specific cleavage after
      piperidine/heat treatment. In contrast, analogues lacking the aza-enediyne
      functionality either fail to interact with DNA (AZB016) or cleave DNA at guanine
      residues, presumably through alkylation of the N-7 position (AZB004). We also
      investigated the cytotoxicity of AZB002 and the related heterocyclic compounds
      AZB004 and AZB016 and find that only the DNA interactive compounds AZB002 and
      AZB004 display significant cytotoxicity. In particular, AZB002 is cytotoxic
      against a wide range of cancer cell lines.

PMID- 11955080
TI  - Catalytic mechanism of enzymes: preorganization, short strong hydrogen bond, and
      charge buffering.
AB  - During the past decade, there has been much debate about the enormous catalytic
      rate enhancement observed in enzymatic reactions involving carbanion
      intermediates. Our recent theoretical study has demonstrated the importance of
      the short strong hydrogen bond (SSHB) in the enzymatic reactions. Nevertheless,
      other recent theoretical studies espouse the role of preorganization over that of
      the SSHB. To achieve a consensus on this issue and to find the truth, a more
      clarified explanation must be given. To this end, we have carried out an
      elaborate analysis of these enzymatic reactions. We here clarify that the
      catalytic mechanism needs to be explained with three important factors, viz.,
      SSHB, preorganization, and charge buffering/dissipation. Since the charge
      buffering role is different from the commonly used concepts of the SSHB and
      preorganization (unless these definitions are expanded), we stress that the
      charge buffering role of the catalytic residues is an important ingredient of the
      enzymatic reaction in reducing the level of accumulation of the negative charge
      on the substrate during the reaction process. This charge reduction is critical
      to the lowering of activation barriers and the stabilization of intermediates.

PMID- 11955079
TI  - Analysis of engineered fibrinogen variants suggests that an additional site
      mediates platelet aggregation and that "B-b" interactions have a role in
      protofibril formation.
AB  - The C-terminal domain of the fibrinogen gamma-chain includes multiple functional
      sites that have been defined in high-resolution structures and biochemical
      assays. Calcium binds to this domain through the side chains of gammaD318 and
      gammaD320 and the backbone carbonyls of gammaF322 and gammaG324. We have examined
      variant fibrinogens with alanine at position gamma318 and/or gamma320 and found
      that calcium binding, fibrin polymerization, and fibrinogen-mediated platelet
      aggregation, but not FXIIIa-catalyzed cross-linking, were abnormal. When measured
      by turbidity, thrombin-catalyzed polymerization was severely reduced, and
      batroxobin-catalyzed polymerization was completely obliterated. Moreover,
      thrombin-catalyzed polymerization was abolished by the peptide GHRP, which binds
      to the polymerization site in the beta-chain but does not inhibit polymerization
      of normal fibrinogen. ADP-induced platelet aggregation was also severely
      impaired. In contrast, as measured by SDS-PAGE, FXIIIa introduced cross-links
      between gamma-chains for all three variants, as expected if the gamma-chain C
      terminal sites were normal. In addition, binding of the monoclonal antibody 4A5,
      which recognizes the C-terminal residues, was not different from normal. These
      data suggest two specific conclusions: (1) a site in the gamma-module other than
      the C-terminus is critical for platelet aggregation and (2) "B-b" interactions
      have a role in protofibril formation.

PMID- 11955081
TI  - Differential effects of temperature on E. coli and synthetic
      polyhydroxybutyrate/polyphosphate channels.
AB  - Complexes of poly-(R)-3-hydroxybutyrate and inorganic polyphosphate (PHB/polyP),
      isolated from the plasma membranes of Escherichia coli or prepared synthetically
      (HB(128)/polyP(65)), form Ca(2+)-selective ion channels in planar lipid bilayers
      that exhibit indistinguishable gating and conductance characteristics at 22
      degrees C. Here we examine the gating and conductance of E. coli and synthetic
      PHB/polyP complexes in planar lipid bilayers as a function of temperature from 15
      to 45 degrees C. E. coli PHB/polyP channels remained effectively open throughout
      this range, with brief closures that became more rare at higher temperatures.
      Conversely, as temperatures were gradually increased, the open probability of
      HB(128)/polyP(65) channels progressively decreased. The effect was fully
      reversible. Channel conductance exhibited three distinct phases. Below 25 degrees
      C, as PHB approached its glass temperature (ca. 10 degrees C), the conductance of
      both E. coli and synthetic channels remained at about the same level (95-105 pS).
      Between 25 degrees C and ca. 40 degrees C, the conductance of E. coli and
      synthetic channels increased gradually with temperature coefficients (Q(10)) of
      1.45 and 1.42, respectively. Above 40 degrees C, E. coli channel conductance
      increased sharply, whereas the conductance of HB(128)/polyP(65) channels leveled
      off. The discontinuities in the temperature curves for E. coli channels coincide
      with discontinuities in thermotropic fluorescence spectra and specific growth
      rates of E. coli cells. It is postulated that E. coli PHB/polyP complexes are
      associated with membrane components that inhibit their closure at elevated
      temperatures.

PMID- 11955082
TI  - The loading and initial elongation modules of rifamycin synthetase collaborate to
      produce mixed aryl ketide products.
AB  - Rifamycin synthetase assembles the chemical backbone that members of the
      rifamycin family of antibiotics have in common. The synthetase contains a mixed
      biosynthetic interface between its loading module, which uses a nonribosomal
      peptide synthetase mechanism, and its initial elongation module, which uses a
      polyketide synthase mechanism. Biochemical studies of the loading and initial
      elongation modules of rifamycin synthetase reveal that this bimodular protein (LM
      M1) catalyzes the formation of the phenyl ketide 3-hydroxy-2-methyl-3
      phenylpropionate via a series of reactions that require benzoate, Mg.ATP,
      methylmalonyl-CoA, and NADPH. The overall rate of phenyl ketide production
      appears to be determined by the covalent loading of benzoate onto LM-M1, rather
      than by subsequent steps such as intermodular transfer of benzoate or
      condensation of benzoate and methylmalonate. Substituted benzoates that have
      previously been shown to be substrates for the loading module alone can also be
      incorporated into the corresponding aryl ketides by LM-M1, suggesting that the
      bimodular protein has a broad substrate tolerance. Discrimination between the
      substituted benzoates appears to reside in the benzoate loading reaction, and
      preincubation of LM-M1 with substituted benzoates and Mg.ATP allows faster
      downstream reactions to be unmasked. LM-M1 may be a useful biochemical system for
      exploring interactions between nonribosomal peptide synthetase and polyketide
      synthase modules.

PMID- 11955084
TI  - Invariant information and quantum state estimation.
AB  - The invariant information, introduced by C. Brukner and A. Zeilinger [Phys. Rev.
      Lett. 83, 3354 (1999)], is reconsidered from the point of view of quantum state
      estimation. We show that this quantity is directly related to the mean error of
      the standard reconstruction from the measurement of a complete set of mutually
      complementary observables. We give its generalization in terms of the Fisher
      information. Provided that the optimum reconstruction is adopted, the information
      loses its invariant character.

PMID- 11955083
TI  - SecB modulates the nucleotide-bound state of SecA and stimulates ATPase activity.
AB  - In Escherichia coli, the formation of SecA-SecB complexes has a direct effect on
      SecA ATPase activity. The mechanism of this interaction was evaluated and defined
      using controlled trypsinolysis, equilibrium dialysis at low temperature, and
      kinetic analyses of the SecA ATPase reaction. The proteolysis data indicate that
      SecB and the nonhydrolyzable ATP analogue AMP-P-C-P induce similar conformational
      changes in SecA which result in a more open or extended structure that is
      suggestive of the ATP-bound form. The effect is synergistic and concentration
      dependent, and requires the occupation of both the high- and low-affinity
      nucleotide binding sites for maximum effect. The equilibrium dialysis experiments
      and kinetic data support the observation that the SecB-enhanced SecA ATPase
      activity is the result of an increased rate of ATP hydrolysis rather than an
      increase in the affinity of ATP for SecA and that the high-affinity nucleotide
      binding site is conformationally regulated by SecB. It appears that SecB may
      function as an intermolecular regulator of ATP hydrolysis by promoting the ATP
      bound state of SecA. The inhibition of SecA ATPase activity by sodium azide in
      the presence of IMVs and a functional signal peptide further indicates that SecB
      promotes the ATP-bound form of SecA.

PMID- 11955085
TI  - Density modulations of Bose-Einstein condensates via laser-induced interactions.
AB  - We show that the dipole-dipole interatomic forces induced by an off-resonant
      running laser beam can lead to a self-bound pencil-shaped Bose condensate, even
      if the laser beam is a plane wave. For an appropriate laser intensity the ground
      state has a quasi-one-dimensional density modulation-a Bose-Einstein
      "supersolid."

PMID- 11955086
TI  - Monte Carlo tests of stochastic Loewner evolution predictions for the 2D self
      avoiding walk.
AB  - The conjecture that the scaling limit of the two-dimensional self-avoiding walk
      (SAW) in a half plane is given by the stochastic Loewner evolution (SLE) with
      kappa = 8/3 leads to explicit predictions about the SAW. A remarkable feature of
      these predictions is that they yield not just critical exponents but also
      probability distributions for certain random variables associated with the self
      avoiding walk. We test two of these predictions with Monte Carlo simulations and
      find excellent agreement, thus providing numerical support to the conjecture that
      the scaling limit of the SAW is SLE(8/3).

PMID- 11955087
TI  - Time-varying alpha and particle physics.
AB  - We argue that models in which an observable variation of the fine structure
      constant is explained by motion of a cosmic scalar field are not stable under
      renormalization and require massive fine-tuning that cannot be explained by any
      known mechanism.

PMID- 11955088
TI  - Semileptonic b-->u decays: lepton invariant mass spectrum.
AB  - We compute O(alpha(2)(s)) QCD corrections to the lepton invariant mass spectrum
      in the decay b-->ulnu(l), relevant for the determination of the Cabibbo-Kobayashi
      Maskawa matrix element /V(ub)/. Our method can also be used to evaluate moments
      of the lepton energy distribution with an O(alpha(2)(s)) accuracy. The Abelian
      part of our result gives the neutrino invariant mass spectrum in the muon decay
      and, upon integration, the O(alpha(2)) correction to the muon lifetime.

PMID- 11955089
TI  - Omega, J/psi, and psi(') production in nuclear collisions and quark-gluon-plasma
      hadronization.
AB  - The transverse mass spectra of Omega, J/psi, and psi' in Pb+Pb collisions at 158A
      GeV are studied within a hydrodynamical model of the quark-gluon-plasma expansion
      and hadronization. The model reproduces the existing data with the common
      hadronization parameters: temperature T = T(H) congruent with 170 MeV and average
      collective transverse velocity v(T) congruent with 0.2.

PMID- 11955090
TI  - Charged and superconducting vortices in dense quark matter.
AB  - Quark matter at astrophysical densities may contain stable vortices due to the
      spontaneous breaking of hypercharge symmetry by kaon condensation. We argue that
      these vortices could be both charged and electrically superconducting. Current
      carrying loops (vortons) could be long-lived and play a role in the magnetic and
      transport properties of this matter. We provide a scenario for vorton formation
      in protoneutron stars.

PMID- 11955091
TI  - Kinetic equation for gluons in the background gauge of QCD.
AB  - We derive the quantum kinetic equation for a pure gluon plasma, applying the
      background field and closed-time-path method. The derivation is more general and
      transparent than earlier works. A term in the equation is found which, as in the
      classical case, corresponds to the color charge precession for partons moving in
      the gauge field.

PMID- 11955092
TI  - Photoionization microscopy.
AB  - We present the first experimental results of a technique called photoionization
      microscopy. Photoelectrons ejected in threshold photoionization of Xe are
      detected in a velocity map imaging apparatus, and interferences between various
      trajectories by which the electron moves from the atom to the detector are
      observed. The structure of the interference pattern, which contains the
      transverse component of the electronic wave function, evolves smoothly with the
      excess energy above the saddle point. The main observed features are interpreted
      within the framework of the semiclassical approximation.

PMID- 11955093
TI  - Direct probe of the bent and linear geometries of the core-excited Renner-Teller
      pair states by means of the triple-ion-coincidence momentum imaging technique.
AB  - The doubly degenerate core-excited Pi state of CO2 splits into two due to static
      Renner-Teller effect. Using the triple-ion-coincidence momentum imaging technique
      and focusing on the dependence of the measured quantities on the polarization of
      the incident light, we have probed, directly and separately, the linear and bent
      geometries for the B1 and A1 Renner-Teller pair states, as a direct proof of the
      static Renner-Teller effect.

PMID- 11955094
TI  - Alternate gradient focusing and deceleration of a molecular beam.
AB  - Neutral dipolar molecules can be decelerated and trapped using time-varying
      inhomogeneous electric fields. This has been demonstrated only for molecules in
      low-field seeking states, but can, in principle, be performed on molecules in
      high-field seeking states as well. Transverse stability is then much more
      difficult to obtain, however, since molecules in high-field seeking states always
      experience a force towards the electrodes. Here we demonstrate that an array of
      dipole lenses in alternate gradient configuration can be used to maintain
      transverse stability. A pulsed beam of metastable CO in high-field seeking states
      is accelerated from 275 to 289 m/s as well as decelerated from 275 to 260 m/s.

PMID- 11955095
TI  - Macrodimers: ultralong range Rydberg molecules.
AB  - We study long range interactions between two Rydberg atoms and predict the
      existence of ultralong range Rydberg dimers with equilibrium distances of many
      thousands of Bohr radii. We calculate the dispersion coefficients C5, C6, and C8
      for two rubidium atoms in the same excited level np and find that they scale like
      n(8), n(11), and n(15), respectively. We show that for certain molecular
      symmetries these coefficients lead to long range potential wells that can support
      molecular bound levels. Such macrodimers would be very sensitive to their
      environment and could probe weak interactions. We suggest experiments to detect
      these macrodimers.

PMID- 11955096
TI  - Transmission of 3 keV Ne7+ ions through nanocapillaries etched in polymer foils:
      evidence for capillary guiding.
AB  - We report unprecedented transmission experiments of 3 keV Ne7+ ions through
      capillaries of 100 nm diameter and 10 microm length produced by etching ion
      tracks in a polymer foil. We studied foils tilted up to +/-20 degrees for which
      the incident ions are forced to interact with the capillary surface.
      Surprisingly, the majority of Ne7+ ions were found to survive the surface
      scattering events in their initial charge state. The angular distributions of the
      transmitted particles indicate propagation of the Ne7+ ions along the capillary
      axis. This capillary guiding of the Ne7+ ion provides evidence that the inner
      walls of the capillaries become charged and electron capture from the surface is
      suppressed in a self-organizing process.

PMID- 11955097
TI  - Controlling the carrier-envelope phase of ultrashort light pulses with optical
      parametric amplifiers.
AB  - The phase link between signal, idler, and pump waves in a parametric interaction
      allows generation of an idler pulse with a phase independent of that of the input
      pulse. We suggest the use of a white-light seeded optical parametric amplifier as
      a self-stabilized source of few-cycle pulses, in which the phase of the electric
      field is exactly reproduced in each laser shot.

PMID- 11955098
TI  - Spatiotemporal optical modulation instability of coherent light in
      noninstantaneous nonlinear media.
AB  - We report on the theoretical derivation and experimental observation of
      spatiotemporal modulation instability (MI) of a coherent light beam in
      noninstantaneous nonlinear media. We obtain analytically the MI growth rate as a
      function of the spatial and temporal frequencies of the perturbation and the
      material response time. In the experiment, we observe that the varying speed of
      the MI patterns increases with the decreased material response time. We also
      observe that increasing the material response time can arrest the MI, agreeing
      with our theoretical derivation.

PMID- 11955099
TI  - Brillouin propagation modes in optical lattices: interpretation in terms of
      nonconventional stochastic resonance.
AB  - We report the first direct observation of Brillouin-like propagation modes in a
      dissipative periodic optical lattice. This has been done by observing a resonant
      behavior of the spatial diffusion coefficient in the direction corresponding to
      the propagation mode with the phase velocity of the moving intensity modulation
      used to excite these propagation modes. Furthermore, we show theoretically that
      the amplitude of the Brillouin mode is a nonmonotonic function of the strength of
      the noise corresponding to the optical pumping, and discuss this behavior in
      terms of nonconventional stochastic resonance.

PMID- 11955101
TI  - Analytical model of nonlinear, single-mode, classical Rayleigh-Taylor instability
      at arbitrary Atwood numbers.
AB  - An analytical model of the nonlinear bubble evolution of single-mode, classical
      Rayleigh-Taylor instability at arbitrary Atwood numbers (A(T)) is presented. The
      model is based on an extension of Layzer's theory [Astrophys. J. 122, 1 (1955)]
      previously applied only to the fluid-vacuum interfaces (A(T) = 1). The model
      provides a continuous bubble evolution from the earlier exponential growth to the
      nonlinear regime when the bubble velocity saturates at U(b) = square root of
      [2A(T)/(1+A(T)) (g/C(g)k)], where k is the perturbation wave number, g is the
      interface acceleration, and C(g) = 3 and C(g) = 1 for the two-dimensional and
      three-dimensional geometries, respectively.

PMID- 11955100
TI  - Convective and absolute Eckhaus instability leading to modulated waves in a
      finite box.
AB  - We report an experimental study of the secondary modulational instability of a
      one-dimensional nonlinear traveling wave in a long bounded channel. Two
      qualitatively different instability regimes involving fronts of spatiotemporal
      defects are linked to the convective and absolute nature of the instability. Both
      transitions appear to be subcritical. The spatiotemporal defects control the
      global mode structure.

PMID- 11955102
TI  - Universal behavior of entrainment due to coherent structures in turbulent shear
      flow.
AB  - A solution is suggested for a persistent mystery in the physics of turbulent
      flows: cumulus clouds rise to towering heights, practically without entraining
      the ambient medium, while apparently similar turbulent jets quickly lose their
      identity through entrainment and mixing. Dynamical system computations on a model
      vortical flow show that entrainment due to coherent structures depends
      sensitively on relative speeds of fluid parcels. Local heating, for example, can
      alter drastically the sizes of Kolmogorov-Arnol'd-Moser tori and chaotic mixing
      regions. The entrainment rate and, hence, the lifetime of a turbulent shear flow
      show a universal, nonmonotone dependence on the heating.

PMID- 11955103
TI  - Observation of shear-wave Mach cones in a 2D dusty-plasma crystal.
AB  - Mach cones composed of shear waves were observed experimentally in a two
      dimensional screened-Coulomb crystal. Highly charged microspheres suspended in a
      plasma and interacting with a repulsive Yukawa potential arranged themselves in a
      triangular lattice with hexagonal symmetry. Mach cones were excited by applying a
      force from the radiation pressure of a moving laser beam. They had a single-cone
      structure, which is explained by the almost dispersionless character of shear
      waves. The cone's opening angle obeyed the Mach-cone-angle relation. Results are
      compared to a molecular-dynamics simulation.

PMID- 11955104
TI  - Macroscopic evidence of soliton formation in multiterawatt laser-plasma
      interaction.
AB  - A novel physical phenomenon has been observed following the interaction of an
      intense (10(19) W/cm(2)) laser pulse with an underdense plasma. Long-lived,
      macroscopic bubblelike structures have been detected through the deflection that
      the associated electric charge separation causes in a proton probe beam. These
      structures are interpreted as the remnants of a cloud of relativistic solitons
      generated in the plasma by the ultraintense laser pulse. This interpretation is
      supported by an analytical study of the soliton cloud evolution, by particle-in
      cell simulations, and by a reconstruction of the proton-beam deflection.

PMID- 11955105
TI  - Light filaments in air for ultraviolet and infrared wavelengths.
AB  - The propagation of femtosecond UV laser pulses in air is numerically shown to
      form intense light filaments over several tenths of Rayleigh lengths. We compare
      UV filamentation with IR filamentation and show that the balance of the physical
      processes supporting the filaments is identical in both cases. For IR and UV
      wavelengths, it is shown that the intensity in the filament and the density of
      the electron plasma created by ionization of air molecules reach similar values
      as high as 10(14) W/cm(2) and 10(17) cm(-3). Spectral data exhibit a large
      broadening in the IR filament and a limited one for UV, which justifies the white
      light generation associated with IR filamentation only.

PMID- 11955107
TI  - Structure-dependent vibrational lifetimes of hydrogen in silicon.
AB  - The lifetimes of the Si-H vibrational stretch modes of the H(*)(2) ( 2062 cm(-1))
      and HV.VH((110)) ( 2072.5 cm(-1)) defects in crystalline Si are measured directly
      by transient bleaching spectroscopy from 10 K to room temperature. The
      interstitial-type defect H(*)(2) has a lifetime of 4.2 ps at 10 K, whereas the
      lifetime of the vacancy-type complex HV.VH((110)) is 2 orders of magnitude
      longer, 295 ps. The temperature dependence of the lifetime of H(*)(2) is governed
      by TA phonons, while HV.VH((110)) is governed by LA phonons. This behavior is
      attributed to the distinctly different local structure of these defects and the
      accompanying local vibrational modes.

PMID- 11955106
TI  - X-ray emission from betatron motion in a plasma wiggler.
AB  - The successful utilization of an ion channel in a plasma to wiggle a 28.5-GeV
      electron beam to obtain broadband x-ray radiation is reported. The ion channel is
      induced by the electron bunch as it propagates through an underdense 1.4-meter
      long lithium plasma. The quadratic density dependence of the spontaneously
      emitted betatron x-ray radiation and the divergence angle of approximately (1
      3)x10(-4) radian of the forward-emitted x-rays as a consequence of betatron
      motion in the ion channel are in good agreement with theory. The absolute photon
      yield and the peak spectral brightness at 14.2-keV photon energy are estimated.

PMID- 11955108
TI  - Osmium has the lowest experimentally determined compressibility.
AB  - On the basis of high pressure diamond-anvil compression studies for the precious
      metals Ru, Ir, and Os we report the surprising discovery that metallic osmium has
      a lower compressibility than covalently bonded diamond. We also find that Ir and
      Ru are as incompressible as Re. In addition, we have performed first principles
      calculations that confirm the trend in the measured transition metal
      compressibilities.

PMID- 11955109
TI  - Energetics and vibrational states for hydrogen on Pt(111).
AB  - We present a combination of theoretical calculations and experiments for the low
      lying vibrational excitations of H and D atoms adsorbed on the Pt(111) surface.
      The vibrational band states are calculated based on the full three-dimensional
      adiabatic potential energy surface obtained from first-principles calculations.
      For coverages less than three quarters of a monolayer, the observed experimental
      high-resolution electron peaks at 31 and 68 meV are in excellent agreement with
      the theoretical transitions between selected bands. Our results convincingly
      demonstrate the need to go beyond the local harmonic oscillator picture to
      understand the dynamics of this system.

PMID- 11955110
TI  - Geometry of the valence transition induced surface reconstruction of Sm(0001).
AB  - We present a structural determination of the surface reconstruction of the
      Sm(0001) surface using surface x-ray diffraction, scanning tunneling microscopy,
      and ab initio calculations. The reconstruction is associated with a large (22%)
      expansion of the atomic radius for the top monolayer surface Sm atoms. The
      mechanism driving the surface reconstruction in Sm is unique among all elements
      and is connected to the strong correlations of the 4f electrons in Sm and the
      intermediate valence observed in certain Sm compounds. The atoms constituting the
      top monolayer of Sm(0001) have vastly different chemical properties compared to
      the layer underneath and behave as if they were an adsorbate of a different
      chemical species.

PMID- 11955111
TI  - Lattice-spin mechanism in colossal magnetoresistive manganites.
AB  - We present a single-orbital double-exchange model, coupled with cooperative
      phonons (the so called breathing modes of the oxygen octahedra in manganites).
      The model is studied with Monte Carlo simulations. For a finite range of doping
      and coupling constants, a first-order metal-insulator phase transition is found,
      which coincides with the paramagnetic-ferromagnetic phase transition. The
      insulating state is due to the self-trapping of every carrier within an oxygen
      octahedron distortion.

PMID- 11955112
TI  - Effects of a parallel magnetic field on the metal-insulator transition in a
      dilute two-dimensional electron system.
AB  - The temperature dependence of conductivity sigma(T) of a two-dimensional electron
      system in silicon has been studied in parallel magnetic fields B. At B = 0, the
      system displays a metal-insulator transition at a critical electron density
      n(c)(0), and dsigma/dT>0 in the metallic phase. At low fields ( B < or
      approximately equal to 2 T), n(c) increases as n(c)(B)-n(c)(0) proportional,
      variant Bbeta ( beta approximately 1), and the zero-temperature conductivity
      scales as sigma(n(s),B,T = 0)/sigma(n(s),0,0) = f(B(beta)/delta(n)), where
      delta(n) = [n(s)-n(c)(0)]/n(c)(0) and n(s) is electron density, as expected for a
      quantum phase transition. The metallic phase persists in fields of up to 18 T,
      consistent with the saturation of n(c) at high fields.

PMID- 11955113
TI  - Thermopower of an Aharonov-Bohm interferometer: theoretical studies of quantum
      dots in the Kondo regime.
AB  - We report on the thermopower of an Aharonov-Bohm (AB) interferometer with a
      quantum dot in the Kondo regime. The thermopower is anomalously enhanced due to
      the Kondo effect as in heavy fermion systems. In contrast to bulk systems, the
      sign of the thermopower can be changed by adjusting the energy level scheme or
      the particle-hole asymmetry of a dot with the gate voltage. Further the magnitude
      and even the sign of the thermopower in the AB ring can be changed at will with
      varying either magnetic fields or the gate voltages.

PMID- 11955114
TI  - Dephasing times in closed quantum dots.
AB  - Dephasing of one-particle states in closed quantum dots is analyzed within the
      framework of random matrix theory and the master equation. The combination of
      this analysis with recent experiments on the magnetoconductance allows, for the
      first time, the evaluation of the dephasing times of closed quantum dots. These
      dephasing times turn out to be dependent on the mean level spacing and
      significantly enhanced as compared with the case of open dots. Moreover, the
      experimental data available are consistent with the prediction that the dephasing
      of one-particle states in finite closed systems disappears at low enough energies
      and temperatures.

PMID- 11955115
TI  - Photoinduced changes of reflectivity in single crystals of YBa2Cu3O6.5 (ortho
      II).
AB  - We report measurements of the photoinduced change in reflectivity of an untwinned
      single crystal of YBa2Cu3O6.5 in the ortho II structure. The decay rate of the
      transient change in reflectivity is found to decrease rapidly with decreasing
      temperature and, below T(c), with decreasing laser intensity. We interpret the
      decay as a process of thermalization of antinodal quasiparticles, with a rate
      determined by inelastic scattering of quasiparticle pairs.

PMID- 11955116
TI  - Evidence for static magnetism in the vortex cores of ortho-II YBa2Cu3O6.50.
AB  - Evidence for static alternating magnetic fields in the vortex cores of underdoped
      YBa2Cu3O6+x is reported. Muon spin rotation measurements of the internal magnetic
      field distribution of the vortex state of YBa2Cu3O6.50 in applied fields of H = 1
      T and H = 4 T reveal a feature in the high-field tail of the field distribution
      which is not present in optimally doped YBa2Cu3O6.95 and which fits well to a
      model with static magnetic fields in the vortex cores. The magnitude of the
      fields is estimated to be 18(2) G and decreases above T = 10 K. We discuss
      possible origins of the additional vortex core magnetism within the context of
      existing theories.

PMID- 11955117
TI  - Common energy scale for magnetism and superconductivity in underdoped cuprates: a
      muon spin resonance investigation of (Ca(x)La(1-x)) (Ba(1.75
      x)La(0.25+x))Cu3O(y).
AB  - We characterize the spontaneous magnetic field, and determine the associated
      temperature T(g), in the superconducting state of (Ca(x)La(1-x)) (Ba(1.75
      x)La(0.25+x)) Cu(3)O(y) using zero and longitudinal field muon spin resonance
      measurements for various values of x and y. Our major findings are (i) T(g) and
      T(c) are controlled by the same energy scale, (ii) the phase separation between
      hole poor and hole rich regions is a microscopic one, and (iii) spontaneous
      magnetic fields appear gradually with no moment size evolution.

PMID- 11955118
TI  - Critical dynamics of gauge systems: spontaneous vortex formation in 2D
      superconductors.
AB  - We examine the formation of vortices during the nonequilibrium relaxation of a
      high-temperature initial state of an Abelian-Higgs system. We equilibrate the
      scalar and gauge fields using gauge-invariant Langevin equations and relax the
      system by instantaneously removing thermal fluctuations. For couplings near
      critical, kappa(c) = square root[lambda]/e = 1, we observe the formation of large
      clusters of like-sign magnetic vortices. Their appearance has implications for
      the dynamics of the phase transition, for the distribution of topological
      defects, and for late-time phase ordering kinetics. We offer explanations for
      both the observed vortex densities and vortex configurations.

PMID- 11955119
TI  - Electrical resistivity anisotropy from self-organized one dimensionality in high
      temperature superconductors.
AB  - We investigate the manifestation of stripes in the in-plane resistivity
      anisotropy in untwinned single crystals of La2-xSrxCuO4 ( x = 0.02-0.04) and
      YBa(2)Cu(3)O(y) ( y = 6.35-7.0). It is found that both systems show strongly
      temperature-dependent in-plane anisotropy in the lightly hole-doped region and
      that the anisotropy in YBa(2)Cu(3)O(y) grows with decreasing y below
      approximately 6.60 despite the decreasing orthorhombicity, which gives most
      direct evidence that electrons self-organize into a macroscopically anisotropic
      state. The transport is found to be easier along the direction of the spin
      stripes already reported, demonstrating that the stripes are intrinsically
      conducting in cuprates.

PMID- 11955120
TI  - Noncollinear ferromagnetism in (III,Mn)V semiconductors.
AB  - We investigate the stability of the collinear ferromagnetic state in kinetic
      exchange models for (III,Mn)V semiconductors with randomly distributed Mn ions.
      Our results suggest that noncollinear ferromagnetism is common to these
      semiconductor systems. The instability of the collinear state is due to long
      range fluctuations involving a large fraction of the localized magnetic moments.
      We address conditions that favor the occurrence of noncollinear ground states and
      discuss unusual behavior that we predict for the temperature and field dependence
      of its saturation magnetization.

PMID- 11955121
TI  - Effect of optical spin injection on ferromagnetically coupled Mn spins in the III
      V magnetic alloy semiconductor (Ga,Mn)As.
AB  - We report on the new type of photoinduced magnetization in ferromagnetic
      (Ga,Mn)As thin films. Optically generated spin-polarized holes change the
      orientation of ferromagnetically coupled Mn spins and cause a large change in
      magnetization, being 15% of the saturation magnetization, without the application
      of a magnetic field. The memorization effect has also been found as a trace after
      the photoinduced magnetization. The observed results suggest that a small amount
      of nonequilibrium carrier spins can cause collective rotation of Mn spins
      presumably through the p-d exchange interaction.

PMID- 11955122
TI  - Direct measurement of the spin Hamiltonian and observation of condensation of
      magnons in the 2D frustrated quantum magnet Cs2CuCl4.
AB  - We propose a method for measuring spin Hamiltonians and apply it to the spin- 1/2
      Heisenberg antiferromagnet Cs2CuCl4, which shows a 2D fractionalized resonating
      valence bond state at low fields. By applying strong fields we fully align the
      spin moment of Cs2CuCl4, transforming it into an effective ferromagnet. In this
      phase the excitations are conventional magnons and their dispersion relation
      measured using neutron scattering give the exchange couplings directly, which are
      found to form an anisotropic triangular lattice with small Dzyaloshinskii-Moriya
      terms. Using the field to control the excitations we observe Bose condensation of
      magnons into an ordered ground state.

PMID- 11955123
TI  - Collapse of valence transition in Yb0.8Y0.2InCu4: pressure-induced weak
      ferromagnetism.
AB  - We investigated the magnetization of Yb0.8Y0.2InCu4 as a function of temperature
      down to 0.6 K, pressure up to 1.2 GPa, and magnetic field up to 9 T. The valence
      transition temperature of Yb0.8Y0.2InCu4 is lowered with applying pressure. At
      0.8 GPa, collapse of the valence transition and ferromagnetic ordering occur
      almost simultaneously. The ferromagnetic phase at 1.2 GPa is characterized by a
      low Curie temperature of 1.7 K and an extremely small ordered moment of 0.05
      micro(B) per Yb. Some effect of screening the ordered moment may play a key role
      in the ferromagnetism and the valence transition.

PMID- 11955124
TI  - Fluorescence decay time of single semiconductor nanocrystals.
AB  - We present fluorescence decay measurements of single ZnS covered CdSe
      nanocrystals. It is shown that the fluorescence decay time is fluctuating during
      the investigation leading to a multiexponential decay even for a single
      nanocrystal. In combination with measurements of the fluorescence blinking
      behavior we find that a high fluorescence intensity is correlated with a long
      fluorescence decay time. This is consistent with a model of fluctuating
      nonradiative decay channels leading to variable dynamic quenching processes of
      the excited state.

PMID- 11955125
TI  - Implementation of quantum search algorithm using classical Fourier optics.
AB  - We report on an experiment on Grover's quantum search algorithm showing that
      classical waves can search a N-item database as efficiently as quantum mechanics
      can. The transverse beam profile of a short laser pulse is processed iteratively
      as the pulse bounces back and forth between two mirrors. We directly observe the
      sought item being found in approximately square root[N] iterations, in the form
      of a growing intensity peak on this profile. Although the lack of quantum
      entanglement limits the size of our database, our results show that entanglement
      is neither necessary for the algorithm itself, nor for its efficiency.

PMID- 11955126
TI  - Experimental realization of quantum games on a quantum computer.
AB  - We generalize the quantum prisoner's dilemma to the case where the players share
      a nonmaximally entangled states. We show that the game exhibits an intriguing
      structure as a function of the amount of entanglement with two thresholds which
      separate a classical region, an intermediate region, and a fully quantum region.
      Furthermore this quantum game is experimentally realized on our nuclear magnetic
      resonance quantum computer.

PMID- 11955127
TI  - Role of protein-water hydrogen bond dynamics in the protein dynamical transition.
AB  - The role of water in protein dynamics has been investigated using molecular
      dynamics simulations of crystals and a dehydrated powder. On the 100 ps time
      scale, the anharmonic and diffusive motions involved in the protein structural
      relaxation are correlated with the protein-water hydrogen bond dynamics. The
      complete structural relaxation of the protein requires relaxation of the hydrogen
      bond network via solvent translational displacement. Inhibiting the solvent
      translational mobility, and therefore the protein-water hydrogen bond dynamics,
      has an effect on the protein relaxation similar to dehydration.

PMID- 11955128
TI  - Helfrich repulsion and dynamical phase separation of multicomponent lipid
      bilayers.
AB  - Thermal fluctuations of surfactant bilayers in an aqueous solution produce an
      effective, long-range repulsion that can lead to a continuous unbinding
      transition. We report on an optical interferometry study of the thermal
      fluctuations of multicomponent bilayers close to the unbinding transition. We
      find that, in contrast to the case of single-component bilayers, the thermal
      fluctuation spectrum of multicomponent bilayers does not agree with a continuous
      unbinding transition but instead indicates the proximity of an unbinding
      tricritical point.

PMID- 11955129
TI  - Synchronization of noise-induced bursts in noncoupled sensory neurons.
AB  - We report experimental observation of phase synchronization in an array of
      nonidentical noncoupled noisy neuronal oscillators, due to stimulation with
      external noise. The synchronization derives from a noise-induced qualitative
      change in the firing pattern of single neurons, which changes from a
      quasiperiodic to a bursting mode. We show that at a certain noise intensity the
      onsets of bursts in different neurons become synchronized, even though the number
      of spikes inside the bursts may vary for different neurons. We demonstrate this
      effect both experimentally for the electroreceptor afferents of paddlefish, and
      numerically for a canonical phase model, and characterize it in terms of
      stochastic synchronization.

PMID- 11955130
TI  - Experimental and numerical studies of noise-induced coherent patterns in a
      subexcitable system.
AB  - A subexcitable medium of Belousov-Zhabotinsky (BZ) reaction subjected to external
      Gaussian white noise is studied in experiments and numerical simulations. We
      observe that at an optimal level of noise the wave sources of excited traveling
      waves become synchronous, as though there exists a long distance spatial
      correlation. The synchronous behavior fades if the noise level becomes larger or
      smaller. Numerical simulations confirm the experimental findings, and point out
      that the best synchronous behavior takes place when the signal-to-noise ratio of
      waves becomes largest.

PMID- 11955131
TI  - Universal topological properties of two-dimensional trivalent cellular patterns.
AB  - Universal topological properties of two-dimensional trivalent cellular patterns
      are found from shell analysis of soap froth and computer-generated Voronoi
      diagrams. We introduce a cluster analysis based on the shell model and find the
      universal relation ln(a/mu(2)) = A+Bln(mu(2)), with the generalized Aboav
      parameter a and second moment of the number of cell edge distribution mu(2). For
      the second, third, and fourth shells of the cluster, A and B are the same for all
      samples. Furthermore, A is increasing with shell number while B is a universal
      number, -0.90. For the first shell, the slope B is the same for soap froths, but
      slightly different from Voronoi graphs.

PMID- 11955132
TI  - Truncation of power law behavior in "scale-free" network models due to
      information filtering.
AB  - We formulate a general model for the growth of scale-free networks under
      filtering information conditions-that is, when the nodes can process information
      about only a subset of the existing nodes in the network. We find that the
      distribution of the number of incoming links to a node follows a universal
      scaling form, i.e., that it decays as a power law with an exponential truncation
      controlled not only by the system size but also by a feature not previously
      considered, the subset of the network "accessible" to the node. We test our model
      with empirical data for the World Wide Web and find agreement.

PMID- 11955133
TI  - Comment on "Kondo resonance in a mesoscopic ring coupled to a quantum dot: exact
      results for the Aharonov-Bohm-Casher effects".

PMID- 11955135
TI  - Comment on "Strong vortex liquid correlation from multiterminal measurements on
      untwinned YBa(2)Cu(3)O(7-delta) single crystals".

PMID- 11955137
TI  - Simple method to make asymptotic series of Feynman diagrams converge.
AB  - We show that, for two nontrivial lambda phi(4) problems (the anharmonic
      oscillator and the Landau-Ginzburg hierarchical model), improved perturbative
      series can be obtained by cutting off the large field contributions. The modified
      series converge to values exponentially close to the exact ones. For lambda
      larger than some critical value, the method outperforms Pade's approximants and
      Borel summations. The method can also be used for series which are not Borel
      summable such as the double-well potential series. We show that semiclassical
      methods can be used to calculate the modified Feynman rules, estimate the error,
      and optimize the field cutoff.

PMID- 11955138
TI  - Critical phenomena of thick branes in warped spacetimes.
AB  - We have investigated the effects of a generic bulk first-order phase transition
      on thick Minkowski branes in warped geometries. As occurs in Euclidean space,
      when the system is brought near the phase transition an interface separating two
      ordered phases splits into two interfaces with a disordered phase in between. A
      remarkable and distinctive feature is that the critical temperature of the phase
      transition is lowered due to pure geometrical effects. We have studied a variety
      of critical exponents and the evolution of the transverse-traceless sector of the
      metric fluctuations.

PMID- 11955139
TI  - Sneutrino-antisneutrino mixing and neutrino mass in anomaly-mediated
      supersymmetry breaking scenario.
AB  - In supersymmetric models with nonzero Majorana neutrino mass, the sneutrino and
      antisneutrino mix, which may lead to same-sign dilepton signals in future
      collider experiments. We point out that the anomaly-mediated supersymmetry
      breaking scenario has a good potential to provide an observable rate of such
      signals for the neutrino masses suggested by the atmospheric and solar neutrino
      oscillations. It is noted also that the sneutrino-antisneutrino mixing can
      provide much stronger information on some combinations of the neutrino masses and
      mixing angles than the neutrino experiments.

PMID- 11955140
TI  - Measurement of the beam-helicity asymmetry in the p((-->)e,e'p)pi(0) reaction at
      the energy of the Delta(1232) resonance.
AB  - In a p((-->)e,e'p)pi(0) out-of-plane coincidence experiment at the three
      spectrometer setup of the Mainz Microtron MAMI, the beam-helicity asymmetry has
      been precisely measured around the energy of the Delta(1232) resonance and Q(2) =
      0.2(GeV/c)(2). The results are in disagreement with three up-to-date model
      calculations. This is interpreted as a lack of understanding of the nonresonant
      background, which in dynamical models is related to the pion cloud.

PMID- 11955141
TI  - Rotational damping in ytterbium nuclei.
AB  - We have made the first clear measurements of rotational damping widths in nuclei.
      In a mixture of three Yb nuclei, these widths are 300 +/- 60 keV between 1.2 and
      1.5 MeV gamma-ray energy [approximately (37-57)Planck's constant]. Compound
      damping and motional narrowing are discussed in connection with these results.

PMID- 11955142
TI  - Experimental evidence of core modification in the near drip-line nucleus 23O.
AB  - The longitudinal momentum (P(axially)) distributions of one- and two-neutron
      removal fragments ((21,22)O) of 23O from the reaction with a C target at 72 A MeV
      have been measured for the first time using a new direct time-of-flight method
      with nearly full acceptance for the breakup fragments. The unexpectedly narrow
      width of 21O ( 115 +/- 34 MeV/c in FWHM) is consistent with two neutrons
      occupying the 2s(1/2) orbital in 23O. This indicates modification of core (22O)
      structure for neutron halo-like sd shell nuclei near the drip line. This also
      suggests the lowering of the s orbital providing a justification for the N = 16
      magic number.

PMID- 11955143
TI  - Exact stochastic mean-field approach to the fermionic many-body problem.
AB  - We investigate a reformulation of the dynamics of interacting fermion systems in
      terms of a stochastic extension of time-dependent Hartree-Fock equations. From a
      path-integral representation of the evolution operator, we show that the exact N
      body state can be interpreted as a coherent average over Slater determinants
      evolving in a random mean-field. The imaginary time propagation is also presented
      and gives a similar scheme which converges to the exact ground state. In
      addition, the growth of statistical errors is examined to show the stability of
      this stochastic formulation.

PMID- 11955144
TI  - Solvated electrons in very small clusters of polar molecules: (HF)(3)(-).
AB  - Photoelectron spectra of (HF)(3)(-) reveal coexistence of two anionic isomers
      with vertical electron detachment energies (VDE) of 0.24 and 0.43 eV. The results
      of electronic-structure calculations, performed at the coupled cluster level of
      theory with single, double, and noniterative triple excitations, suggest that the
      two isomers observed experimentally are an open, zigzag, dipole-bound anion and
      an asymmetric solvated electron, in which the dipole-bound anion of (HF)(2) is
      solvated by one HF monomer at the side of the excess electron. The theoretical
      VDE of 0.21 and 0.44 eV, respectively, are in excellent agreement with the
      experimental data.

PMID- 11955145
TI  - rf Spectroscopy with a single Ba+ ion.
AB  - We have employed the method of shelving to measure Zeeman resonances of a single
      trapped Ba+ ion. We use optical pumping to place the ion in a selected magnetic
      sublevel of either the 6S(1/2) ground state or the 5D(3/2) metastable state. The
      ion is exposed to an rf field, and a probing/shelving mechanism detects whether
      spin-flip transitions have taken place. We have observed rf transitions with
      linewidths of 15 Hz, limited by magnetic-field noise. We have also observed the
      shift in the Zeeman frequency when the ion is illuminated by off-resonant light.
      A simultaneous measurement of such light shifts in two atomic states of Ba+ will
      permit a precise determination of the ratio of transition matrix elements.

PMID- 11955146
TI  - Charge localization in collision-induced multiple ionization of van der Waals
      clusters with highly charged ions.
AB  - Charge localization in multiple ionization and fragmentation of small argon
      clusters is reported. The processes are initiated by interaction of the neutral
      cluster with highly charged Xe(q+) (5< or =q< or =25). Products are detected by
      means of multicoincidence time-of-flight methods. A strong dependence of the
      fragmentation pattern on the Xe charge state q is observed. In particular, we
      find evidence for formation of multiply charged atomic Ar(r+) fragment ions up to
      r = 7. Such high charge states have neither been observed in fission of multiply
      charged van der Waals clusters nor in ion-induced fragmentation of fullerenes or
      metal clusters. This hints at fundamentally different excitation and
      fragmentation dynamics.

PMID- 11955147
TI  - Generating and probing a two-photon fock state with a single atom in a cavity.
AB  - A two-photon Fock state is prepared in a cavity sustaining a "source mode" and a
      "target mode," with a single circular Rydberg atom. In a third-order Raman
      process, the atom emits a photon in the target while scattering one photon from
      the source into the target. The final two-photon state is probed by measuring by
      Ramsey interferometry the cavity light shifts induced by the target field on the
      same atom. Extensions to other multiphoton processes and to a new type of
      micromaser are briefly discussed.

PMID- 11955148
TI  - Finite-size effects on intensity correlations in random media.
AB  - The correlations between waves transmitted through random media are analyzed by
      use of a random-matrix approach and numerical simulations of rough waveguides.
      Although the intensity and conductance fluctuations are practically independent
      of the sample length, the correlations present a strong dependence on the length
      of the disordered region. In waveguide geometries the long-range correlations
      C((2)) and C((3)), usually associated to intensity and conductance fluctuations,
      respectively, become negative as the length of the system decreases. Our results
      provide a new interpretation of recent optical experiments on disordered slab
      geometries.

PMID- 11955149
TI  - Opening optical four-wave mixing channels with giant enhancement using ultraslow
      pump waves.
AB  - We show that by strongly modifying the dispersion properties of a four-level
      system, non-existing wave mixing channels can be opened and significantly
      enhanced. Specifically, we show that coherent optical four-wave mixing with a
      pump wave mediated by electromagnetically induced transparency (thereby
      propagating with an extremely slow group velocity) will lead to many orders of
      magnitude enhancement in the amplitude of the generated wave. Contrary to common
      belief, a large transparency window, which causes a large propagation velocity,
      actually diminishes efficient mixing wave production.

PMID- 11955150
TI  - Broadband fivefold reduction of vacuum fluctuations probed by dyes in photonic
      crystals.
AB  - We observed for the first time a strong angle-independent modification of
      spontaneous emission spectra from laser dyes in photonic crystals, made of
      inverse opals in titania. Comparison with spectra from such crystals with much
      smaller lattice spacing, for which emission is in the long wavelength limit,
      reveals inhibition of emission up to a factor approximately 5 over a large
      bandwidth of 13% of the first order Bragg resonance frequency. The center
      frequency and bandwidth of the inhibition agree with calculated total density of
      states, while the measured inhibition of vacuum fluctuations is much larger.
      Because of the specific location of the dye molecules, we likely probe the
      strongly modulated local photonic density of states.

PMID- 11955151
TI  - Autonomous bursting in a homoclinic system.
AB  - The output of a dynamical system in a regime of homoclinic chaos transforms from
      a continuous train of irregularly spaced spikes to clusters of regularly spaced
      spikes with quiescent periods in between (bursting), provided a low frequency
      portion of the output is fed back. We provide experimental evidence of such an
      autonomous bursting by a CO2 laser with feedback. The phenomena here presented
      are extremely robust against noise and display qualitative analogies with
      bursting phenomena in neurons.

PMID- 11955152
TI  - Superbunch hadron colliders.
AB  - A novel concept of a high luminosity hadron collider is proposed. This would be a
      typical application of an induction synchrotron being newly developed. Extremely
      long bunches, referred to as superbunches, are generated by a multibunch stacking
      method employing barrier buckets at the injection into the collider and are
      accelerated with a step voltage induced in the induction gaps. Superbunches
      intersect with each other, yielding a luminosity of more than 10(35) cm(-2) sec(
      1). A combination of vertical crossing and horizontal crossing must be employed
      in order to avoid any significant beam-beam tune shift.

PMID- 11955154
TI  - Evidence for Trivelpiece-Gould modes in a helicon discharge.
AB  - The high ionization efficiency of helicon discharges has been attributed to
      Landau damping and mode coupling to Trivelpiece-Gould (TG) modes. Though theory
      predicts the importance of TG modes, they have rarely been seen. Here they were
      detected directly by measuring their radiofrequency current with a J-dot probe,
      thus supporting the contention that TG modes play a role in these enigmatic
      plasma sources.

PMID- 11955153
TI  - Discharges in the JET tokamak where the safety factor profile is identified as
      the critical factor for triggering internal transport barriers.
AB  - Joint European Torus discharges which demonstrate the critical role the safety
      factor profile, q, can play in the formation of internal transport barriers (ITB)
      are examined. In these discharges, the target parameters, including the E x B
      flows, were kept virtually the same, except for the q profile. In a discharge
      with a nonmonotonic q, an ITB was triggered whereas a discharge with monotone q
      made no such transition. Thus, there is strong evidence that the q profile was
      the critical factor for the triggering of an ITB. Possible interpretations of
      this finding are discussed.

PMID- 11955155
TI  - Ablative Rayleigh-Taylor instability at short wavelengths observed with moire
      interferometry.
AB  - One of the most important quantities to be measured for better understanding of
      the ablative Rayleigh-Taylor (RT) instability is the growth rate in the short
      wavelength region at which the RT instability is significantly reduced. The short
      wavelength ( 4.7-12 microm) RT growth rates for direct-drive targets were
      measured for the first time by utilizing the innovated moire interferometry [M.
      Matsuoka et al., Rev. Sci. Instrum. 70, 637 (1999)]. These growth rates were
      reasonably well reproduced by the simulation that solves the Fokker-Planck
      equation for nonlocal heat transport.

PMID- 11955157
TI  - Calculation of hydrodynamic mass for atomic impurities in helium.
AB  - We present a simple numerical procedure for calculating the irrotational
      hydrodynamic flow around a spherical solute in superfluid helium. The results for
      alkali cations are compared to recent many-body variational Monte Carlo (VMC)
      calculations. The helium contribution to the effective masses calculated by the
      VMC and hydrodynamic methods are 12.9(4.6) versus 9.4 u for Li+, 48.2(5.6) versus
      52.1 u for Na+, 69.6(4.8) versus 70.1 u for K+, and 6.4(8.8) versus 6.8 for Cs+.
      In all cases, the agreement of the two results are in within the error estimate
      of the VMC calculation, demonstrating the accuracy of hydrodynamic treatment of
      helium motion even on the atomic length scale.

PMID- 11955156
TI  - JET quasistationary internal-transport-barrier operation with active control of
      the pressure profile.
AB  - Quasistationary operation has been achieved on the Joint European Torus tokamak
      in internal-transport-barrier (ITB) scenarios, with the discharge time limited
      only by plant constraints. Full current drive was obtained over all the high
      performance phase by using lower hybrid current drive. For the first time
      feedback control on the total pressure and on the electron temperature profile
      was implemented by using, respectively, the neutral beams and the ion-cyclotron
      waves. Although impurity accumulation could be a problem in steady state ITBs,
      these experiments bring some elements to answer to it.

PMID- 11955158
TI  - Supercurrent through hybrid junctions with anisotropic Cooper-pair condensates.
AB  - A general formula for the supercurrent between different internal structures in a
      wide class of hybrid junctions is derived on the basis of the Andreev-reflection
      picture. The formula extends existing formulas and also enables us to analyze
      novel B-phase/A-phase/B-phase junctions in superfluid 3He systems. We propose a
      mechanism for pi states due to the (circumflex)l texture in the A phase of the
      junction, which could elucidate major features of the pi states with higher
      critical current ( H states) discovered in superfluid 3He weak links. The
      bistability of the pi states is also discussed.

PMID- 11955159
TI  - Melting at alkyl side chain comb polymer interfaces.
AB  - Infrared visible sum frequency generation (SFG) spectroscopy has been used to
      study structure and melting transition temperatures of alkyl-side chain-acrylate
      comb polymers at air and solid interfaces. At the air interface, the SFG spectra
      show methyl bands and two transitions are observed: the first, near the bulk
      melting temperature, T(m), and the second 10-20 degrees C higher than T(m). The
      shorter the alkyl side chain, the larger the difference between the two
      transition temperatures. In contrast, methylene bands are observed at sapphire
      interface with a single transition near T(m) (C18).

PMID- 11955160
TI  - Dynamic behavior of anisotropic nonequilibrium driving lattice gases.
AB  - It is shown that intrinsically anisotropic nonequilibrium systems relaxing by a
      dynamic process exhibit universal critical behavior during their evolution toward
      nonequilibrium stationary states. An anisotropic scaling ansatz for the dynamics
      is proposed and tested numerically. Relevant critical exponents can be evaluated
      self-consistently using both the short- and long-time dynamics frameworks. The
      obtained results allow us to clarify a long-standing controversy about the
      theoretical description, the universality, and the origin of the anisotropy of
      driven diffusive systems, showing that the standard field theory does not hold
      and supporting a recently proposed alternative theory.

PMID- 11955161
TI  - Pressure dependence of diffusion in simple glasses and supercooled liquids.
AB  - Using molecular dynamics simulation, we have calculated the pressure dependence
      of the diffusion coefficient in a binary Lennard-Jones glass. We observe four
      temperature regimes. The apparent activation volume drops from high values in the
      hot liquid to a plateau value. Near the critical temperature of the mode coupling
      theory it rises steeply, but in the glassy state we find again small values,
      similar to the ones in the liquid. The peak of the activation volume at the
      critical temperature is in agreement with the prediction of mode coupling theory.

PMID- 11955162
TI  - Absolute TiN(111) step energies from analysis of anisotropic island shape
      fluctuations.
AB  - In situ high-temperature (1165-1248 K) scanning tunneling microscopy was used to
      measure fluctuations around the equilibrium shape of two-dimensional vacancy
      islands on TiN(111) terraces. From the equilibrium shape, the ratio of the two
      <110> step energies was found to be 0.72 +/- 0.02. Combining this with the
      results of an exact approach for analysis of shape fluctuations, applicable to
      highly anisotropic islands, we obtain absolute values for step energies and step
      stiffnesses as a function of orientation.

PMID- 11955163
TI  - Landau's quasiparticle mapping: Fermi liquid approach and Luttinger liquid
      behavior.
AB  - A continuous unitary transformation is introduced which realizes Landau's mapping
      of the elementary excitations (quasiparticles) of an interacting Fermi liquid
      system to those of the system without interaction. The conservation of the number
      of quasiparticles is important. The transformation is performed numerically for a
      one-dimensional system, i.e., the worst case for a Fermi liquid approach. Yet
      evidence for Luttinger liquid behavior is found. Such an approach may open a
      route to a unified description of Fermi and Luttinger liquids on all energy
      scales.

PMID- 11955164
TI  - Anomalous conductance distribution in quasi-one-dimensional gold wires: possible
      violation of the one-parameter scaling hypothesis.
AB  - We report measurements of conductance distribution in a set of quasi-one
      dimensional gold wires. The distribution includes the second cumulant or the
      variance which describes the universal conductance fluctuations, and the third
      cumulant which denotes the leading deviation. We have observed an asymmetric
      contribution--or, a nonvanishing third cumulant--contrary to the expectation for
      quasi-one-dimensional systems in the noninteracting theories in the one-parameter
      scaling framework, which include the perturbative diagrammatic calculations and
      the random matrix theory.

PMID- 11955165
TI  - Aharonov-Bohm oscillations with spin: evidence for Berry's phase.
AB  - We report a study of the Aharonov-Bohm effect, the oscillations of the resistance
      of a mesoscopic ring as a function of a perpendicular magnetic field, in a GaAs
      two-dimensional hole system with a strong spin-orbit interaction. The Fourier
      spectra of the oscillations reveal extra structure near the main peak whose
      frequency corresponds to the magnetic flux enclosed by the ring. A comparison of
      the experimental data with results of simulations demonstrates that the origin of
      the extra structure is the geometric (Berry) phase acquired by the carrier spin
      as it travels around the ring.

PMID- 11955166
TI  - Rectifying behavior in Coulomb blockades: charging rectifiers.
AB  - We introduce examples of tunneling and diffusive, Coulomb-regulated rectifiers
      based on the Coulomb blockade formalism in discrete and continuum systems,
      respectively. Nonlinearity of the interacting dynamics profoundly enhances the
      inherent asymmetry of the devices by reducing the Hilbert space of accessible
      states. The discrete charging rectifier is structurally similar to hybrid
      molecular electronic rectifiers, while the continuum-charging rectifier is based
      on a model of ionic flow through a pore (ion channel) with an artificial branch.
      The devices are formally related to ratchet systems with spatial periodicity
      replaced by a winding number: the current.

PMID- 11955167
TI  - Excitonic polarons in semiconductor quantum dots.
AB  - The discretization of the electronic spectrum in semiconductor quantum dots
      implies a strong coupling behavior between the optical phonons and the electron
      hole pairs, despite the fact that a pair is electrically neutral. The excitonic
      polarons strongly modify the optical spectra. In particular, the ground excitonic
      polaron contains one or two phonon components, which leads to the existence of
      phonon replicas in the luminescence. The population and coherence decay times of
      the optical transition associated with the ground excitonic polaron are
      calculated.

PMID- 11955168
TI  - Anomalous optical absorption in the normal state of overdoped cuprates near the
      charge-ordering instability.
AB  - We argue that the hump observed in the optical conductivity at or below a few
      hundreds of cm(-1), in overdoped cuprates such as the electron-doped Nd(2
      x)Ce(x)CuO(4-y) at x > or approximately equal to 0.15 and the hole-doped
      Bi2Sr2CuO6 and La2-xSrxCuO4, cannot be accounted for within a single-fluid
      description. We propose instead an interpretation based on the direct excitation
      of charge collective modes, which become nearly critical in the proximity to a
      charge-ordering instability. Their critical character entails a peculiar
      temperature dependence and a pseudoscaling form of the optical spectra, which
      agree with the experimental data.

PMID- 11955169
TI  - Attraction between pancake vortices in the crossing lattices of layered
      superconductors.
AB  - The intervortex interaction is investigated in very anisotropic layered
      superconductors in tilted magnetic field. In such a case, the crossing lattice of
      Abrikosov vortices (AVs) and Josephson vortices (JVs) appears. The interaction
      between pancake vortices, forming the AVs and JVs, produces the deformation of
      the AV line. It is demonstrated that, as a result of this deformation, a long
      range attraction between AVs is induced. This phenomenon is responsible for the
      dense vortex chain formation. The vortex structure in the weak perpendicular
      magnetic field is the vortex chain phase, where only a small part of JVs is
      occupied by AVs.

PMID- 11955170
TI  - Electromagnetic response of static and fluctuating stripes in cuprate
      superconductors.
AB  - Using infrared spectroscopy, we found that changes in the in-plane charge
      dynamics attributable to static stripe order in La(1.275)Nd(0.6)Sr(0.125)CuO(4)
      or superconductivity in La(1.875)Sr(0.125)CuO(4) are confined to energies smaller
      than 100 cm(-1). An absorption peak in the low- omega conductivity of the Nd
      doped compound is suggestive of localization effects due to the reduced
      dimensionality of static charge stripes. Neither superconductivity nor static
      stripe ordering has a noticeable effect on the depression of the scattering rate
      at omega<1000 cm(-1) characteristic of the pseudogap state in other classes of
      moderately doped cuprates.

PMID- 11955171
TI  - Novel anisotropy in the superconducting gap structure of Bi2Sr2CaCu2O(8+delta)
      probed by quasiparticle heat transport.
AB  - Since the nature of pairing interactions is manifested in the superconducting gap
      symmetry, the exact gap structure, particularly any deviation from the simple
      d(x(2)-y(2)) symmetry, would help in elucidating the pairing mechanism in high-
      T(c) cuprates. Anisotropic heat transport measurement in
      Bi(2)Sr(2)CaCu(2)O(8+delta) reveals that the quasiparticle populations are
      different for the two nodal directions and thus the gap structure must be
      uniquely anisotropic, suggesting that pairing is governed by interactions with a
      rather complicated anisotropy. Intriguingly, it is found that the "plateau" in
      the magnetic-field dependence of the thermal conductivity is observed only in the
      b-axis transport.

PMID- 11955172
TI  - Onset of magnetic order in fcc-Fe films on Cu(100).
AB  - On the basis of an ab initio theory of metallic magnetism in layered materials,
      we investigate the onset of magnetic order in thin (2-8 layers) fcc-Fe films on
      and embedded in Cu(100) substrates. In particular, we find an oscillatory
      dependence of the Curie temperatures on embedding depth, in excellent agreement
      with experimental data. The thermally induced spin fluctuations are treated
      within a mean-field disordered local moment picture and give rise to layer
      dependent "local exchange splittings" in the electronic structure even in the
      paramagnetic phase. These features determine the magnetic intralayer and
      interlayer interactions which are strongly influenced by the presence and extent
      of the Cu cap.

PMID- 11955173
TI  - Precursor states for charge carrier generation in conjugated polymers probed by
      ultrafast spectroscopy.
AB  - Photocurrent experiments using two femtosecond laser pulses are performed on a
      photodiode using a ladder-type conjugated polymer as the active layer. With a
      photon energy of 3.1 eV the first pulse excites singlet excitons. A time-delayed
      second pulse with a photon energy of 2.49 eV leads to a decrease of the
      photocurrent by exciton depletion due to stimulated emission. S1 excitons being
      dissociated during their entire lifetime are identified as the only relevant
      channel for charge carrier generation. Intrachain polaron pairs are also formed
      on an ultrafast time scale with a yield of approximately 10%. They can be
      efficiently dissociated by reexcitation with photons of an energy of 1.9 eV.

PMID- 11955174
TI  - Size dependent ultrafast cooling of water droplets in microemulsions by
      picosecond infrared spectroscopy.
AB  - The ultrafast thermal relaxation of reversed micelles in n-octane/AOT/water
      (where AOT denotes sodium di-2-ethylhexyl sulfosuccinate) microemulsions was
      investigated by time-resolved infrared pump-probe spectroscopy. This picosecond
      cooling process can be described in terms of heat diffusion, demonstrating a new
      method to determine the nanometer radii of the water droplets. The reverse
      micelles are stable against transient temperatures far above the equilibrium
      stability range. The amphiphilic interface layer (AOT) seems to provide an
      efficient heat contact between the water and the nonpolar solvent.

PMID- 11955175
TI  - Monitoring the transitions of the charge-induced reconstruction of Aau(110) by
      reflectance anisotropy spectroscopy.
AB  - Missing-row reconstructions on Au(110) immersed in electrolytes have been studied
      by in situ reflectance anisotropy spectroscopy. Transitions between the 1 x 3, 1
      x 2, and 1 x 1 surface structures were monitored as a function of the applied
      potential. A kinetic model allowed us to reproduce the data satisfactorily. These
      results confirm the theoretical predictions showing that the surface charge
      determines the surface reconstruction. The transition potentials and the
      activation barriers were determined.

PMID- 11955176
TI  - Superinelastic electron transfer: electron trapping in H2O ice via the N
      2((2)Pi(g)) resonance.
AB  - We present measurements on the trapping of 0-3 eV electrons in H2O ice films
      covered with a submonolayer of N2 molecules. At the energy of the N-2((2)Pi(g))
      shape resonance, the absolute cross section for electron trapping in ice is
      approximately 5.5 x 10(-16) cm(2), similar to that for vibrational excitations of
      gaseous N2 via the resonance. This result, indicating that nearly all electrons
      from autoionization of N-2((2)Pi(g)) are transferred to electron traps in ice, is
      explained by superinelastic electron transfer from N-2((2)Pi(g)) into preexisting
      traps in polar ice, leaving N2 in high vibrational excited states.

PMID- 11955177
TI  - Fast nuclear spin relaxation in hyperpolarized solid 129Xe.
AB  - We report extensive new measurements of the longitudinal relaxation time T1 of
      129Xe nuclear spins in solid xenon. For temperatures T<120 K and magnetic fields
      B>0.05 T, we found T1 on the order of hours, in good agreement with previous
      measurements and with the predicted phonon-scattering limit for the spin-rotation
      interaction. For T>120 K, our new data show that T1 can be much shorter than the
      phonon scattering limit. For B = 0.06 T, a field often used to accumulate
      hyperpolarized xenon, T1 is approximately 6 s near the Xe melting point T(m) =
      161.4 K. From T = 50 K to T(m), the new data are in excellent agreement with the
      theoretical prediction that the relaxation is due to (i) modulation of the spin
      rotation interaction by phonons, and (ii) modulation of the dipole-dipole
      interaction by vacancy diffusion.

PMID- 11955178
TI  - Quantum filter for nonlocal polarization properties of photonic qubits.
AB  - We present an optical filter that transmits photon pairs only if they share the
      same horizontal or vertical polarization, without decreasing the quantum
      coherence between these two possibilities. Various applications for entanglement
      manipulations and multiphoton qubits are discussed.

PMID- 11955179
TI  - Synthetic gene network for entraining and amplifying cellular oscillations.
AB  - We present a model for a synthetic gene oscillator and consider the coupling of
      the oscillator to a periodic process that is intrinsic to the cell. We
      investigate the synchronization properties of the coupled system, and show how
      the oscillator can be constructed to yield a significant amplification of
      cellular oscillations. We reduce the driven oscillator equations to a normal
      form, and analytically determine the amplification as a function of the strength
      of the cellular oscillations. The ability to couple naturally occurring genetic
      oscillations to a synthetically designed network could lead to possible
      strategies for entraining and/or amplifying oscillations in cellular protein
      levels.

PMID- 11955180
TI  - Entanglement and decoherence of a micromechanical resonator via coupling to a
      Cooper-pair box.
AB  - We analyze the quantum dynamics of a micromechanical resonator capacitively
      coupled to a Cooper-pair box. With appropriate quantum state control of the
      Cooper box, the resonator can be driven into a superposition of spatially
      separated states. The Cooper box can also be used to probe the decay of the
      resonator superposition state due to environmental decoherence.

PMID- 11955181
TI  - Comment on "Solidification of a supercooled liquid in a narrow channel".

PMID- 11955182
TI  - Comment on "Missing 2k(F) response for composite fermions in phonon drag".

PMID- 11955184
TI  - Conformal field theory interpretation of black hole quasinormal modes.
AB  - We obtain exact expressions for the quasinormal modes of various spin for the
      Banados-Teitelboim-Zanelli black hole. These modes determine the relaxation time
      of black hole perturbations. Exact agreement is found between the quasinormal
      frequencies and the location of the poles of the retarded correlation function of
      the corresponding perturbations in the dual conformal field theory. This then
      provides a new quantitative test of the anti-de Sitter/conformal field theory
      correspondence.

PMID- 11955185
TI  - Cosmological constant from degenerate vacua.
AB  - Under the hypothesis that the cosmological constant vanishes in the true ground
      state with lowest possible energy density, we argue that the observed small but
      finite vacuumlike energy density can be explained if we consider a theory with
      two or more degenerate perturbative vacua, which are unstable due to quantum
      tunneling, and if we still live in one of such states. An example is given making
      use of the topological vacua in non-Abelian gauge theories.

PMID- 11955186
TI  - Solar neutrinos: probing the quasi-isothermal solar core produced by
      supersymmetric dark matter particles.
AB  - SNO measurements strongly constrain the central temperature of the Sun, to within
      a precision of much less than 1%. This result can be used to probe the parameter
      space of supersymmetric dark matter. In this first analysis we find a lower limit
      for the weakly interacting massive particle (WIMP) mass of 60 GeV. Furthermore,
      in the event that WIMPs create a quasi-isothermal core, they will produce a
      peculiar distribution of the solar neutrino fluxes measured on Earth. Typically,
      a WIMP with a mass of 100 GeV and annihilation cross section of 10(-34) cm(3)/sec
      will decrease the neutrino predictions, by up to 4% for the Cl, by 3% for the
      heavy water, and by 1% for the Ga detectors.

PMID- 11955187
TI  - Nonlocal anomaly of the axial-vector current for bound states.
AB  - We argue that the amplitude <rho(gamma)/delta(nu)(q(gamma)(nu)gamma(5)q)/0> does
      not vanish in the limit of zero quark masses. This represents a new kind of
      violation of the classical equation of motion for the axial current and should be
      interpreted as the axial anomaly for bound states. The anomaly emerges in spite
      of the fact that the one loop integrals are ultraviolet finite as guaranteed by
      the finite size of bound-state wave functions. As a result, the amplitude behaves
      like approximately 1/p(2) in the limit of a large momentum p of the current. The
      observed effect requires the modification of the classical equation of motion of
      the axial-vector current by nonlocal operators.

PMID- 11955188
TI  - Noncommutative quantum mechanics from noncommutative quantum field theory.
AB  - We derive noncommutative multiparticle quantum mechanics from noncommutative
      quantum field theory in the nonrelativistic limit. Particles of opposite charges
      are found to have opposite noncommutativity. As a result, there is no
      noncommutative correction to the hydrogen atom spectrum at the tree level. We
      also comment on the obstacles to take noncommutative phenomenology seriously and
      propose a way to construct noncommutative SU(5) grand unified theory.

PMID- 11955189
TI  - Improved direct measurement of A(b) and A(c) at the Z(0) pole using a lepton tag.
AB  - The parity violation parameters A(b) and A(c) of the Zb(b) and Zc(c) couplings
      have been measured directly, using the polar angle dependence of the polarized
      cross sections at the Z(0) pole. Bottom and charmed hadrons were tagged via their
      semileptonic decays. Both the electron and muon analyses take advantage of new
      multivariate techniques to increase the analyzing power. Based on the 1993-1998
      SLD sample of 550,000 Z(0) decays produced with highly polarized electron beams,
      we measure A(b) = 0.919+/-0.030(stat)+/-0.024(syst), and A(c) = 0.583+/
      0.055(stat)+/-0.055(syst).

PMID- 11955193
TI  - Ab initio shell model calculations with three-body effective interactions for p
      shell nuclei.
AB  - We present a qualitative improvement of the ab initio no-core shell model (NCSM)
      approach by implementing three-body interaction capability for p-shell nuclei. We
      report the first calculations using three-body effective interactions derived
      from realistic nucleon-nucleon potentials for 6Li, 8Be, and 10B and demonstrate
      that the use of three-body effective interactions speeds up the convergence of
      the NCSM approach. For 10B, we predict JpiT = 1(+)0 ground state, contrary to the
      experimental observation of 3(+)0, when the AV8(') potential is used, indicating
      the need for true three-body forces.

PMID- 11955192
TI  - Quadrupole moments of highly deformed structures in the A approximately 135
      region: probing the single-particle motion in a rotating potential.
AB  - The latest generation gamma-ray detection system, GAMMASPHERE, coupled with the
      Microball charged-particle detector, has made possible a new class of nuclear
      lifetime measurement. For the first time differential lifetime measurements free
      from common systematic errors for over 15 different nuclei ( >30 rotational bands
      in various isotopes of Ce, Pr, Nd, Pm, and Sm) have been extracted at high spin
      within a single experiment. This comprehensive study establishes the effective
      single-particle transition quadrupole moments in the A approximately 135 light
      rare-earth region. Detailed comparisons are made with theoretical calculations
      using the self-consistent cranked mean-field theory which convincingly
      demonstrates the validity of the additivity of single-particle quadrupole moments
      in this mass region.

PMID- 11955194
TI  - Lyman- alpha(1) decay in hydrogenlike ions: interference between the E1 and M2
      transition amplitudes.
AB  - For the Lyman- alpha(1) transition (2p(3/2)-->1s(1/2)) in hydrogenlike ions an
      interference between the leading E1 decay channel and the much weaker M2
      multipole transition gives rise to a remarkable modified angular distribution of
      the emitted photons from aligned ions. This effect is most pronounced for the
      heaviest elements but results in a still sizable correction for medium- Z ions.
      For the particular case of hydrogenlike uranium where the angular distribution of
      the Lyman- alpha(1) x rays following radiative electron capture has been
      measured, the former variance with theoretical findings is removed when this E1
      M2 interference is taken into account.

PMID- 11955196
TI  - Conical harmonic generation in isotropic materials.
AB  - A novel class of nonlinear optical processes is described in which radiation at
      the nth harmonic is generated through the use of a (2n+1)-order nonlinearity.
      Utilizing an odd-order nonlinearity, this process allows for the generation and
      amplification of both odd- and even-order harmonics in isotropic materials.
      Additionally, this process can always be phase matched in normal-dispersion
      materials without the use of birefringence. Experimental results are presented in
      which conical third-harmonic emission is generated from a sapphire sample.

PMID- 11955195
TI  - Quantifying nonclassicality of one-mode Gaussian states of the radiation field.
AB  - We define the degree of nonclassicality of a one-mode Gaussian state of the
      quantum electromagnetic field in terms of the Bures distance between the state
      and the set of all classical one-mode Gaussian states. We find the closest
      classical Gaussian state and the degree of nonclassicality using a recently
      established expression for the Uhlmann fidelity of two single-mode Gaussian
      states. The decrease of nonclassicality under thermal mapping is carefully
      analyzed. Along the same lines, we finally present the evolution of
      nonclassicality during linear amplification.

PMID- 11955197
TI  - Manifestation of Arnol'd diffusion in quantum systems.
AB  - We study an analog of the classical Arnol'd diffusion in a quantum system of two
      coupled nonlinear oscillators one of which is governed by an external periodic
      force with two frequencies. In a classical model this very weak diffusion happens
      in a narrow stochastic layer along the coupling resonance and leads to an
      increase of the total energy of the system. We show that quantum dynamics of wave
      packets mimics, up to some extent, global properties of the classical Arnol'd
      diffusion. This specific diffusion represents a new type of quantum dynamics and
      may be observed, for example, in 2D semiconductor structures (quantum billiards)
      perturbed by time-periodic external fields.

PMID- 11955198
TI  - Heat conduction in one-dimensional systems with hard-point interparticle
      interactions.
AB  - Results of extensive and accurate numerical studies on heat transfer in a system
      of particles with unequal masses, interacting through hard-point potentials with
      two types of symmetry, are reported. The particles are confined in a one
      dimensional box with fixed ends coupled to heat reservoirs at different
      temperatures. The study aims to throw light upon recent controversial results on
      thermal conductivity in one-dimensional systems. When the particles interact
      through elastic hard-point collisions (a standard asymmetric case), the system is
      shown to have always infinite (anomalous) thermal conductivity as follows from
      the Prosen-Campbell theorem.

PMID- 11955199
TI  - Effect of interfacial liquid structuring on the coherence length in
      nanolubrication.
AB  - The degree of interfacial structuring of n-hexadecane and
      octamethylcyclotetrasiloxane (OMCTS) was measured within a nanometer boundary
      regime to silicon surfaces. Boundary-layer effects on lubricating sliding (in
      terms of a thermodynamic stress activation parameter) and the layer thickness
      were determined by scanning force microscopy. A 2.0+/-0.3 nm thick, entropically
      cooled layer was found for n-hexadecane. Measurements on spherically shaped OMCTS
      molecules exhibited only an interfacial "monolayer," and identified the molecular
      shape of n-hexadecane responsible for augmented interfacial structuring.
      Interfacial liquid structuring was found to reduce friction.

PMID- 11955200
TI  - Anisotropic velocity correlation spectrum at small scales in a homogeneous
      turbulent shear flow.
AB  - A simple theoretical analysis and direct numerical simulations on 512(3) grid
      points suggest that the velocity correlation spectrum tensor in the inertial
      subrange of homogeneous turbulent shear flow at high Reynolds number is given by
      a simple form that is an anisotropic function of the wave vector. The tensor is
      determined by the rate of the strain tensor of the mean flow, the rate of energy
      dissipation per unit mass, the wave vector, and two nondimensional constants.

PMID- 11955201
TI  - Transverse envelope dynamics of a 28.5-GeV electron beam in a long plasma.
AB  - The transverse dynamics of a 28.5-GeV electron beam propagating in a 1.4 m long,
      (0-2)x10(14) cm(-3) plasma are studied experimentally in the underdense or
      blowout regime. The transverse component of the wake field excited by the short
      electron bunch focuses the bunch, which experiences multiple betatron
      oscillations as the plasma density is increased. The spot-size variations are
      observed using optical transition radiation and Cherenkov radiation. In this
      regime, the behavior of the spot size as a function of the plasma density is well
      described by a simple beam-envelope model. Dynamic changes of the beam envelope
      are observed by time resolving the Cherenkov light.

PMID- 11955202
TI  - Dynamics of the critical surface in high-intensity laser-solid interactions:
      modulation of the XUV harmonic spectra.
AB  - The generation of harmonics from the interaction of an intense (I>or=10(18) W cm(
      2)) laser with a solid surface is investigated. Modulation of the harmonic
      emission spectrum with a periodicity of 2 to 4 harmonics is observed at higher
      laser intensities. A similar modulation is predicted by a particle-in-cell
      simulation. The modulation is shown to be caused by the higher modes of
      oscillation of the critical surface during the interaction. As a result, the
      dynamics of the critical surface can be inferred from the shape of the harmonic
      spectrum.

PMID- 11955203
TI  - Elastic property maps of austenitic stainless steels.
AB  - The most recent advances in theory and methodology are directed towards obtaining
      a quantitative description of the electronic structure and physical properties of
      alloy steels. Specifically, we employ ab initio alloy theories to map the elastic
      properties of austenitic stainless steels as a function of chemical composition.
      The so generated data can be used in the search for new steel grades, and, as an
      example, we predict two basic compositions with outstanding properties among the
      austenitic stainless steels.

PMID- 11955204
TI  - Thermodynamic discontinuity between low-density amorphous ice and supercooled
      water.
AB  - A combination of reverse Monte Carlo, molecular dynamics, and lattice dynamics
      simulations were used to obtain structural and thermodynamic data for low-density
      amorphous ice. A thermodynamically discontinuous transformation to a phase with
      properties and a structure consistent with supercooled liquid water is found to
      occur at approximately 130 K. Quantum corrections have a profound effect on
      thermodynamic properties and the location of important thermodynamic points in
      the water phase diagram.

PMID- 11955191
TI  - Direct search for charged higgs bosons in decays of top quarks.
AB  - We present a search for charged Higgs bosons in decays of pair-produced top
      quarks in pp collisions at sqrt[s] = 1.8 TeV recorded by the D0 detector at the
      Fermilab Tevatron collider. With no evidence for signal, we exclude most regions
      of the ( M(H+/-),tan(beta)) parameter space where the decay t--> H(+)b has a
      branching fraction >0.36 and B(H+/--->tau(nu)(tau)) is large.

PMID- 11955205
TI  - Structure of Rb-III: novel modulated stacking structures in alkali metals.
AB  - The crystal structure of Rb-III, stable between 13 and 17 GPa, has been
      determined from quasi-single-crystal x-ray diffraction data. It is orthorhombic,
      space group C222(1), with 52 atoms in the unit cell, and has an 8-10-8-8-10-8
      stacking of 8- and 10-atom layers. The recently reported 84-atom structure of Cs
      III can be understood as an 8-8-10-8-8-8-8-10-8-8 stacking of the same layers.
      These represent a new class of modulated elemental structures.

PMID- 11955206
TI  - Mobility transition of solid rare gases in confined environments.
AB  - We report the results of x-ray diffraction and small angle scattering studies of
      Ar and Kr confined in sol-gel and Vycor glasses. The confined liquid crystallizes
      in a disordered hcp structure on freezing. Upon further cooling a sharp
      transition occurs at a reduced temperature of T/T(m) approximately 0.65, where
      the crystalline structure disappears and the total scattering decreases. This
      behavior marks the onset of a well-defined mobility transition, where the
      confined sample migrates out of the pore space.

PMID- 11955207
TI  - Observation of columnar microstructure in step-graded Si1-xGex/Si films using
      high-resolution X-ray microdiffraction.
AB  - Columnar microstructure in step-graded Si(1-x)Ge(x)/Si(001) structures with low
      threading dislocation densities has been determined using high angular resolution
      (approximately 0.005 degrees ) x-ray microdiffraction. X-ray rocking curves of a
      3-microm-thick strain-relaxed Si(0.83)Ge(0.17) film show many sharp peaks and can
      be simulated with a model having a set of Gaussians having narrow angular widths
      (0.013 degrees -0.02 degrees ) and local ranges of tilt angles varying from 0.05
      degrees to 0.2 degrees. These peaks correspond to individual tilted rectangular
      columnar micrograins having similar (001) lattice spacings and average areas of
      0.8 to 2.0 microm(2).

PMID- 11955208
TI  - Long jumps in the surface diffusion of large molecules.
AB  - We have studied the diffusion of the two organic molecules DC and HtBDC on the
      Cu(110) surface by scanning tunneling microscopy. Surprisingly, we find that long
      jumps, spanning multiple lattice spacings, play a dominating role in the
      diffusion of these molecules--the root-mean-square jump lengths are as large as
      3.9 and 6.8 lattice spacings, respectively. The presence of long jumps is
      revealed by a new and simple method of analysis, which is tested by kinetic Monte
      Carlo simulations.

PMID- 11955190
TI  - Diffractive dijet production at sqrt[s] = 630 and 1800 GeV at the Fermilab
      Tevatron.
AB  - We report a measurement of the diffractive structure function F(D)(jj) of the
      antiproton obtained from a study of dijet events produced in association with a
      leading antiproton in pp collisions at sqrt[s] = 630 GeV at the Fermilab
      Tevatron. The ratio of F(D)(jj) at sqrt[s] = 630 GeV to F(D)(jj) obtained from a
      similar measurement at sqrt[s] = 1800 GeV is compared with expectations from QCD
      factorization and other theoretical predictions. We also report a measurement of
      the xi ( x-Pomeron) and beta ( x of parton in Pomeron) dependence of F(D)(jj) at
      sqrt[s] = 1800 GeV. In the region 0.035<xi<0.095, /t/<1 GeV2, and beta<0.5,
      F(D)(jj)(beta,xi) is found to be of the form beta(-1.0+/-0.1)xi(-0.9+/-0.1),
      which obeys beta-xi factorization.

PMID- 11955209
TI  - Origin of compressive residual stress in polycrystalline thin films.
AB  - We present a model for compressive stress generation during thin film growth in
      which the driving force is an increase in the surface chemical potential caused
      by the deposition of atoms from the vapor. The increase in surface chemical
      potential induces atoms to flow into the grain boundary, creating a compressive
      stress in the film. We develop kinetic equations to describe the stress evolution
      and dependence on growth parameters. The model is used to explain measurements of
      relaxation when growth is terminated and the dependence of the steady-state
      stress on growth rate.

PMID- 11955210
TI  - Thiol diffusion and the role of humidity in "Dip Pen Nanolithography".
AB  - The radii of octadecanethiol spots deposited by an atomic force microscope tip
      onto a gold surface were studied as a function of contact time and humidity. The
      deposition is well described by two-dimensional diffusion from an annular source
      of constant concentration, with a surface diffusion coefficient of 8400 nm(2) s(
      1), independent of humidity. Facile transfer is observed even after near
      continuous deposition for more than 24 h in a dry N2 environment, indicating that
      a water meniscus is not required.

PMID- 11955211
TI  - Multiwall carbon nanotubes as quantum dots.
AB  - We have measured the differential conductance of individual multiwall carbon
      nanotubes. Coulomb blockade and energy level quantization are observed. The
      electron levels are nearly fourfold degenerate (including spin) and their
      evolution in magnetic field (Zeeman splitting) agrees with a g factor of 2. In
      zero magnetic field the sequential filling of states evolves with spin S
      according to S = 0-->1/2-->0.... A Kondo enhancement of the conductance is
      observed when the number of electrons on the tube is odd.

PMID- 11955212
TI  - Work functions at facet edges.
AB  - We perform ab initio pseudopotential calculations for metal crystals with finite
      facets of different crystallographic orientation to investigate the work function
      profile near crystal edges. We examine local edge effects, and address the
      problem of the coexistence of different face-dependent local work functions at
      crystal edges. By modeling the electronic dipoles at the metal surface, we show
      how nonvanishing surface charges spontaneously appear on metals with inequivalent
      facets. Our studies of Al crystal nanowires with (100) and (111) facets are
      extended to derive the dependence of the work function on the crystal morphology
      in the macroscopic limit.

PMID- 11955213
TI  - Subharmonic shapiro steps and assisted tunneling in superconducting point
      contacts.
AB  - We analyze the current in a superconducting point contact of arbitrary
      transmission in the presence of a microwave radiation. The interplay between the
      ac Josephson current and the microwave signal gives rise to Shapiro steps at
      voltages V = (m/n)h(omega)(r)/2e, where n,m are integer numbers and omega(r) is
      the radiation frequency. The subharmonic steps (n not equal 1) are a consequence
      of multiple Andreev reflections (MAR) and provide a signature of the peculiar ac
      Josephson effect at high transmission. Moreover, the dc current exhibits a rich
      subgap structure due to photon-assisted MARs.

PMID- 11955214
TI  - Electronic structure of MgB2 from angle-resolved photoemission spectroscopy.
AB  - The first angle-resolved photoemission spectroscopy results from MgB2 single
      crystals are reported. Along the GammaK and GammaM directions, we observed three
      distinct dispersive features approaching the Fermi energy. These can be assigned
      to the theoretically predicted sigma (B 2p(x,y)) and pi (B 2p(z)) bands. In
      addition, a small parabolic-like band is detected around the Gamma point, which
      can be attributed to a surface-derived state. The overall agreement between our
      results and the band calculations suggests that the electronic structure of MgB2
      is of a conventional nature, thus implying that electron correlations are weak
      and may be of little importance to superconductivity in this system.

PMID- 11955215
TI  - Individual domain wall resistance in submicron ferromagnetic structures.
AB  - The resistance generated by individual domain walls is measured in a FePd
      nanostructure. Combining transport and magnetic imaging measurements, the
      intrinsic domain wall resistance is quantified. It is found positive and of a
      magnitude consistent with that predicted by models based on spin scattering
      effects within the walls. This magnetoresistance at a nanometer scale allows a
      direct counting of the number of walls inside the nanostructure. The effect is
      then used to measure changes in the magnetic configuration of submicron stripes
      under application of a magnetic field.

PMID- 11955216
TI  - Coarsening of antiferromagnetic domains in multilayers: the key role of
      magnetocrystalline anisotropy.
AB  - The domain structure of an antiferromagnetic superlattice is studied. Synchrotron
      Mossbauer and polarized neutron reflectometric maps show micrometer-size primary
      domain formation as the external field decreases from saturation to remanence. A
      secondary domain state consisting mainly of at least 1 order of magnitude larger
      domains is created when a small field along the layer magnetizations induces a
      bulk-spin-flop transition. The domain-size distribution is reproducibly dependent
      on the magnetic prehistory. The condition for domain coarsening is shown to be
      the equilibrium of the external field energy with the anisotropy energy.

PMID- 11955217
TI  - Correlated magnetic vortex chains in mesoscopic cobalt dot arrays.
AB  - Nucleation and annihilation of vortex states have been studied in two-dimensional
      arrays of densely packed cobalt dots. A clear signature of dipolar interactions
      both between single-domain state dots and vortex state dots has been observed
      from the dependence of vortex nucleation and annihilation fields on interdot
      separation. A direct consequence of these interactions is the formation of vortex
      chains as well as dipole chains aligned along the direction of the external
      field. In addition, short range correlation of chiralities within vortex chains
      has been observed using magnetic force microscopy imaging and has been attributed
      to cross-talking between adjacent elements.

PMID- 11955219
TI  - Two-species mixture of quantum degenerate Bose and Fermi gases.
AB  - We have produced a macroscopic quantum system in which a 6Li Fermi sea coexists
      with a large and stable 23Na Bose-Einstein condensate. This was accomplished
      using interspecies sympathetic cooling of fermionic 6Li in a thermal bath of
      bosonic 23Na. The system features rapid thermalization and long lifetimes.

PMID- 11955218
TI  - Complex local dynamics in DNA on the picosecond and nanosecond time scales.
AB  - Time-resolved Stokes shift measurements of the local structural relaxation of
      three DNA oligonucleotides are presented. Logarithmic relaxation is seen for over
      three decades in time (40 ps-40 ns), indicating a complex relaxation among a
      large number of conformational substates. The observed relaxation is the same in
      all the sequences. Sequence dependence of the localized dynamics of DNA does not
      appear within this time range. We infer that 30%-50% of the relaxation is faster
      than 40 ps, has a nonlogarithmic decay and has a sequence dependent amplitude.

PMID- 11955220
TI  - Bose-enhanced chemistry: amplification of selectivity in the dissociation of
      molecular Bose-Einstein condensates.
AB  - We study the photodissociation chemistry of a quantum degenerate gas of bosonic
      triatomic ABC molecules, assuming two open rearrangement channels ( AB+C or
      A+BC). The equations of motion are equivalent to those of a parametric multimode
      laser, resulting in an exponential buildup of macroscopic mode populations. By
      exponentially amplifying a small differential in the single-particle rate
      coefficients, Bose stimulation leads to a nearly complete selectivity of the
      collective N-body process, indicating a novel type of ultraselective quantum
      degenerate chemistry.

PMID- 11955221
TI  - Kinetics and scaling in ballistic annihilation.
AB  - We study the simplest irreversible ballistically controlled reaction, whereby
      particles having an initial continuous velocity distribution annihilate upon
      colliding. In the framework of the Boltzmann equation, expressions for the
      exponents characterizing the density and typical velocity decay are explicitly
      worked out in arbitrary dimension. These predictions are in excellent agreement
      with the complementary results of extensive Monte Carlo and molecular dynamics
      simulations. We finally discuss the definition of universality classes indexed by
      a continuous parameter for this far from equilibrium dynamics with no
      conservation laws.

PMID- 11955222
TI  - Neutrino cross sections and future observations of ultrahigh-energy cosmic rays.
AB  - We show that future detectors of ultrahigh-energy cosmic-ray neutrinos will be
      able to measure neutrino-nucleon cross section, sigma(nu N), at energies as high
      as 10(11) GeV or higher. We find that the flux of upgoing charged leptons per
      unit surface area produced by neutrino interactions below the surface is
      inversely proportional to sigma(nu N). This contrasts with the rate of horizontal
      air showers (HAS) due to neutrino interactions in the atmosphere, which is
      proportional to sigma(nu N). Thus, by comparing the HAS and upgoing air shower
      rates, the neutrino-nucleon cross section can be inferred. Taken together,
      upgoing and horizontal rates ensure a healthy total event rate, regardless of the
      value of sigma(nu N).

PMID- 11955223
TI  - Observability of earth-skimming ultrahigh energy neutrinos.
AB  - Neutrinos with energies above 10(8) GeV are expected from cosmic ray interactions
      with the microwave background and are predicted in many speculative models. Such
      energetic neutrinos are difficult to detect, as they are shadowed by Earth, but
      rarely interact in the atmosphere. Here we propose a novel detection strategy:
      Earth-skimming neutrinos convert to charged leptons that escape Earth, and these
      leptons are detected in ground level fluorescence detectors. With the existing
      HiRes detector, neutrinos from some proposed sources are marginally detectable,
      and improvements of 2 orders of magnitude are possible at the proposed Telescope
      Array.

PMID- 11955224
TI  - Noncommutative quantum cosmology.
AB  - We propose a model for noncommutative quantum cosmology by means of a deformation
      of minisuperspace. For the Kantowski-Sachs metric we are able to find the exact
      wave function. We construct wave packets and show that new quantum states that
      "compete" to be the most probable state appear, in clear contrast with the
      commutative case. A tunneling process could be possible among these states.

PMID- 11955225
TI  - Dimming supernovae without cosmic acceleration.
AB  - We present a simple model where photons propagating in extragalactic magnetic
      fields can oscillate into very light axions. The oscillations may convert some of
      the photons, departing a distant supernova, into axions, making the supernova
      appear dimmer and hence more distant than it really is. Averaging over different
      configurations of the magnetic field we find that the dimming saturates at about
      one-third of the light from the supernovae at very large redshifts. This results
      in a luminosity distance versus redshift curve almost indistinguishable from that
      produced by the accelerating Universe, if the axion mass and coupling scale are m
      approximately 10(-16) eV, M approximately 4 x 10(11) GeV. This phenomenon may be
      an alternative to the accelerating Universe for explaining supernova
      observations.

PMID- 11955226
TI  - A high statistics measurement of the Lambda(+)(c) lifetime.
AB  - A high statistics measurement of the Lambda(+)(c) lifetime from the Fermilab
      fixed-target FOCUS photoproduction experiment is presented. We describe the
      analysis technique with particular attention to the determination of the
      systematic uncertainty. The measured value of 204.6 +/- 3.4 (stat) +/- 2.5 (syst)
      fs from 8034 +/- 122 Lambda(+)(c)-->pK(-)pi(+) decays represents a significant
      improvement over the present world average.

PMID- 11955229
TI  - Neutron polarizabilities investigated by quasifree Compton scattering from the
      deuteron.
AB  - Measuring Compton scattered photons and recoil neutrons in coincidence, quasifree
      Compton scattering by the neutron has been investigated at MAMI (Mainz) at
      theta(lab)(gamma) = 136 degrees in an energy range from 200 to 400 MeV. From the
      data a polarizability difference of alpha(n)-beta(n) = 9.8+/-3.6(stat)+2.1
      1.1(syst)+/-2.2(model) in units of 10(-4) fm(3) has been determined. In
      combination with the polarizability sum alpha(n)+beta(n) = 15.2+/-0.5 deduced
      from photoabsorption data, the first precise results for the neutron electric and
      magnetic polarizabilities, alpha(n) = 12.5+/-1.8(stat)+1.1-0.6(syst)+/-1.1(model)
      and beta(n) = 2.7-/+1.8(stat)+0.6-1.1(syst)-/+1.1(model), are obtained.

PMID- 11955230
TI  - Spinor bosonic atoms in optical lattices: symmetry breaking and
      fractionalization.
AB  - We study superfluid and Mott insulator phases of cold spin-1 Bose atoms with
      antiferromagnetic interactions in an optical lattice, including a usual polar
      condensate phase, a condensate of singlet pairs, a crystal spin nematic phase,
      and a spin singlet crystal phase. We suggest a possibility of exotic
      fractionalized phases of spinor Bose-Einstein condensates and discuss them in the
      language of Z2 lattice gauge theory.

PMID- 11955231
TI  - Feedback on the motion of a single atom in an optical cavity.
AB  - We demonstrate feedback on the motion of a single neutral atom trapped in the
      light field of a high-finesse cavity. Information on the atomic motion is
      obtained from the transmittance of the cavity. This is used to implement a
      feedback loop in analog electronics that influences the atom's motion by
      controlling the optical dipole force exerted by the same light that is used to
      observe the atom. In spite of intrinsic limitations, the time the atom stays
      within the cavity could be extended by almost 30% beyond that of a comparable
      constant-intensity dipole trap.

PMID- 11955232
TI  - Helium-antihydrogen interaction: the Born-Oppenheimer potential energy curve.
AB  - The interaction of atomic antihydrogen with helium has been studied within the
      Born-Oppenheimer approximation. The linear combination of explicitly correlated
      Gaussian functions was used as the ansatz for the wave function of light
      particles. The potential energy curve with the minimum at 3.63 bohr and the
      barrier at 2.42 bohr has been obtained.

PMID- 11955233
TI  - Enhancement of positron-atom annihilation near the positronium formation
      threshold.
AB  - The behavior of the positron- 2 gamma annihilation rate on an atomic target near
      the positronium (Ps) formation threshold is determined. When the positron energy
      epsilon approaches the threshold epsilon(thr) from below, the effective number of
      electrons contributing to the annihilation, Z(eff), grows as Z(eff) approximately
      A/square root of [epsilon(thr)-epsilon], where A is related to the size of the Ps
      formation cross section, sigma(Ps) approximately B square root of [epsilon
      epsilon(thr)], by A = B square root of [2 epsilon(thr)]/32 pi (in atomic units).
      Taking account of the finite Ps lifetime eliminates the singularity in Z(eff) and
      shows that close to threshold the positron annihilation cross section is
      identical to the para-Ps formation cross section.

PMID- 11955234
TI  - Focal spots of size lambda/23 open up far-field fluorescence microscopy at 33 nm
      axial resolution.
AB  - We report spots of excited molecules of 33 nm width created with focused light of
      lambda = 760 nm wavelength and conventional optics along the optic axis. This is
      accomplished by exciting the molecules with a femtosecond pulse and subsequent
      depletion of their excited state with red-shifted, picosecond-pulsed,
      counterpropagating, coherent light fields. The lambda/23 ratio constitutes what
      is to our knowledge the sharpest spatial definition attained with freely
      propagating electromagnetic radiation. The sub-diffraction spots enable for the
      first time far-field fluorescence microscopy with resolution at the tens of
      nanometer scale, as demonstrated in images of membranes of bacillus megaterium.

PMID- 11955228
TI  - Measurement of the lifetime difference in D0 meson decays.
AB  - We report a measurement of the D0-D macro(0) mixing parameter y(CP) using 23.4
      fb(-1) of data collected near the Upsilon(4S) resonance with the Belle detector
      at KEKB. y(CP) is measured from the lifetime difference of D0 mesons decaying
      into the K(-)pi(+) state and the CP-even eigenstate K(-)K(+). We find y(CP) = (
      0.5+/-1.0(+0.7)(-0.8))x10(-2), where the first error is statistical and the
      second is systematic, corresponding to a 95% confidence interval 
      0.030<y(CP)<0.020.

PMID- 11955235
TI  - Patterning of small particles by a surfactant-enhanced Marangoni-Benard
      instability.
AB  - Evaporating drops provide a means of organizing particles suspended within them.
      Here, the manner in which surfactants alter these patterns is studied as a
      function of the surface state of an insoluble monolayer at the drop interface.
      The surface state is visualized throughout the drop evolution using fluorescence
      microscopy. A regime of surfactant coverage is identified that creates conditions
      that enhance the Marangoni-Benard instability. This result was not anticipated in
      prior studies, in which surfactants are predicted to prevent this instability.
      These data demonstrate that, by tuning the liquid-gas boundary condition, the
      patterns formed from an evaporating drop can be controlled.

PMID- 11955236
TI  - Storing, retrieving, and processing optical information by Raman backscattering
      in plasmas.
AB  - By employing stimulated Raman backscattering in a plasma, information carried by
      a laser pulse can be captured in the form of a very slowly propagating plasma
      wave that persists for a time long compared with the pulse duration. If the
      plasma is then probed with a short laser pulse, the information stored in the
      plasma wave can be retrieved in a second scattered electromagnetic wave. The
      recording and retrieving processes can conserve robustly the pulse shape, thus
      enabling the recording and retrieving with fidelity of information stored in
      optical signals.

PMID- 11955237
TI  - Coulomb explosion and thermal spikes.
AB  - A fast ion can electronically excite a solid producing a track of damage, a
      process initially used to detect energetic particles but now used to alter
      materials. From the seminal paper by Fleischer et al. [Phys. Rev. 156, 353
      (1967)] to the present, "Coulomb explosion" and thermal spike models have been
      often treated as competing models for describing ion track effects. Here
      molecular dynamics simulations of electronic sputtering, a surface manifestation
      of track formation, show that in the absence of significant quenching Coulomb
      explosion in fact produces a spike at high excitation density, but the standard
      spike models are incorrect.

PMID- 11955238
TI  - Raman spectroscopic investigation of H2, HD, and D2 physisorption on ropes of
      single-walled, carbon nanotubes.
AB  - We have observed the S- and Q-branch Raman spectra of H2, HD, and D2 adsorbed at
      85 K and pressures up to 8 atm on single-walled, carbon nanotubes (SWNT).
      Comparative data for H2 on graphite and C60 were also collected. Frequency
      downshifted and upshifted features were observed in the Q-branch spectra of H2 on
      C60 and SWNT. These shifts are small and are therefore inconsistent with charge
      transfer. An H2-surface potential with van der Waals and electrostatic terms was
      developed and used to estimate the shifts in the frequency of the Q(0) transition
      of H2 adsorbed in two types of sites. These calculations corroborate the
      experimental findings and indicate physisorption in multiple sites of the SWNT
      ropes.

PMID- 11955239
TI  - Diffusion mechanism of hydrogen in amorphous silicon: ab initio molecular
      dynamics simulation.
AB  - The mechanism of H migration in amorphous Si has remained an unresolved problem.
      The main issue is the small activation energy (1.5 eV) relative to the known
      strength of Si-H bonds (2-3.5 eV). We report first-principles finite-temperature
      simulations which demonstrate vividly that H is not released spontaneously, as
      proposed by most models, but awaits the arrival of a floating bond (FB). The
      "migrating species" is an FB-H complex, with H jumping from Si to Si and the FB
      literally floating around it. Migration stops when the FB veers away.

PMID- 11955240
TI  - Surface segregation of Ge at SiGe(001) by concerted exchange pathways.
AB  - The segregation of Ge during growth on SiGe(001) surfaces was investigated by ab
      initio calculations. Four processes involving adatoms rather than ad-dimers were
      considered. The two most efficient channels proceed by the concerted exchange
      mechanism and involve a swap between an incorporated Ge and a Si adatom, or
      between Si and Ge in the first and the second surface layers, respectively. The
      calculated activation energies of approximately 1.5 eV explain well the high
      temperature experimental data. Segregation mechanisms involving step edges are
      much less efficient.

PMID- 11955241
TI  - Total energy method from many-body formulation.
AB  - The fruitfulness of traditional many-body Green's function theory for calculating
      the total energy of real systems is demonstrated using the random phase
      approximation in the Luttinger-Ward formulation. As the first application to a
      real system, the total energy of H2 is calculated as a function of nuclear
      separation and compared with the configuration interaction and the local density
      approximation results. While the local density result is in large error for large
      separations, the present approach gives satisfactory agreement with the
      configuration interaction results. The method is promising as an alternative to
      the quantum Monte Carlo technique.

PMID- 11955227
TI  - Upsilon production and polarization in p p macro collisions at square root of s =
      1.8 TeV.
AB  - We report on measurements of the Upsilon(1S), Upsilon(2S), and Upsilon(3S)
      differential cross sections (d(2)sigma/dp(T)dy)(/y/<0.4), as well as on the
      Upsilon(1S) polarization in p p macro collisions at square root of s = 1.8 TeV
      using a sample of 77+/-3 pb(-1) collected by the collider detector at Fermilab.
      The three resonances were reconstructed through the decay Upsilon-->mu(+)mu(-).
      The measured angular distribution of the muons in the Upsilon(1S) rest frame is
      consistent with unpolarized meson production.

PMID- 11955242
TI  - Nonadiabatic Car-Parrinello molecular dynamics.
AB  - An extension of Car-Parrinello (CP) molecular dynamics for efficient treatment of
      electronically nonadiabatic processes is presented. The current approach couples
      the S1 restricted open-shell Kohn-Sham excited state to the S0 ground state using
      a surface hopping scheme. Efficient evaluation of the nonadiabatic couplings is
      achieved by exploiting the available wave function time derivatives. Since the
      computational cost scales linearly with the number of excited states, the
      technique makes possible nonadiabatic ab initio simulations of systems of similar
      complexity to those typically studied by standard CP methods. It is thus ideally
      suited to study the photochemistry of large molecules, particularly in condensed
      phases.

PMID- 11955243
TI  - Spin-resolved unoccupied electronic band structure from quantum size oscillations
      in the reflectivity of slow electrons from ultrathin ferromagnetic crystals.
AB  - The spin-dependent reflectivity of electrons with energies between 0 and 20 eV
      from Fe single crystals 2-8 monolayers thick on a W(110) surface is studied by
      spin-polarized low energy electron microscopy. The quantum size oscillations in
      the reflectivity are analyzed in a similar manner as in photoemission of ground
      state electrons, yielding the spin-resolved unoccupied state band structure of Fe
      in the Gamma N direction in the energy range studied.

PMID- 11955245
TI  - Broken unitarity and phase measurements in Aharonov-Bohm interferometers.
AB  - Aharonov-Bohm mesoscopic solid-state interferometers yield a conductance which
      contains a term cos(phi+beta), where phi relates to the magnetic flux.
      Experiments with a quantum dot on one of the interfering paths aim to relate beta
      to the dot's intrinsic Friedel transmission phase alpha(1). For closed systems,
      which conserve the electron current (unitarity), the Onsager relation requires
      that beta = 0 or pi. For open systems, we show that in general beta depends on
      the details of the broken unitarity. Although it gives information on the
      resonances of the dot, beta is generally not equal to alpha(1). A direct relation
      between beta and alpha(1) requires specific ways of opening the system, which are
      discussed.

PMID- 11955244
TI  - Mediation of long range charge transfer by Kondo bound States.
AB  - We present a theory of nonequilibrium long range charge transfer between donor
      and acceptor centers in a model polymer mediated by magnetic exciton (Kondo)
      bound states. Our model produces electron tunneling lengths easily exceeding 10
      A, as observed recently in DNA and organic charge transfer systems. This long
      ranged tunneling is effective for weak to intermediate donor-bridge coupling, and
      is enhanced both by weak to intermediate strength Coulomb hole-electron
      attraction (through the orthogonality catastrophe) and by coupling to local
      vibrational modes.

PMID- 11955246
TI  - Energy loss of atoms at metal surfaces due to electron-hole pair excitations:
      first-principles theory of "chemicurrents".
AB  - A method is presented for calculating electron-hole pair excitation due to an
      incident atom or molecule interacting with a metal surface. Energy loss is
      described using an ab initio approach that obtains a position-dependent friction
      coefficient for an adsorbate moving near a metal surface from a total energy
      pseudopotential calculation. A semiclassical forced oscillator model is
      constructed to describe excitation of the electron gas due to the incident
      molecule. This approach is applied to H and D atoms incident on a Cu(111)
      surface, and we obtain theoretical estimates of the "chemicurrents" measured by
      Nienhaus et al. [Phys. Rev. Lett. 82, 446 (1999)] for these atoms incident on the
      surface of a Schottky diode.

PMID- 11955247
TI  - Two-dimensional metal in a parallel magnetic field.
AB  - We have investigated the effect of an in-plane parallel magnetic field
      (B(axially) on two high mobility metallic-like dilute two-dimensional hole gas
      systems in GaAs quantum wells. The experiments reveal that, while suppressing the
      magnitude of the low temperature resistance drop, B(axially) does not affect
      E(a), the characteristic energy scale of the metallic resistance drop. The field
      B(c) at which the metallic-like resistance drop vanishes is dependent on both the
      width of the quantum well and the orientation of B(axially). It is unexpected
      that E(a) is unaffected by B(axially) up to B(c) despite the fact that the Zeeman
      energy at B(c) is roughly equal to E(a).

PMID- 11955248
TI  - Dynamics of quantum phase transition in an array of Josephson junctions.
AB  - We study the dynamics of the Mott insulator-superfluid quantum phase transition
      in a periodic 1D array of Josephson junctions. We show that crossing the critical
      point at a finite rate with a quench time tau(Q) induces finite quantum
      fluctuations of the current around the loop proportional to tau(-1/6)(Q). This
      scaling could be experimentally verified with an array of weakly coupled Bose
      Einstein condensates or superconducting grains.

PMID- 11955249
TI  - Anomalous dispersion of longitudinal optical phonons in
      Nd(1.86)Ce(0.14)CuO(4+delta) determined by inelastic x-ray scattering.
AB  - The phonon dispersions of Nd(1.86)Ce(0.14)CuO(4+delta) along the [xi,0,0]
      direction have been determined by inelastic x-ray scattering. Compared to the
      undoped parent compound, the two highest longitudinal phonon branches, associated
      with the Cu-O bond stretching and out-of-plane oxygen vibration, are shifted to
      lower energies. Moreover, an anomalous softening of the bond-stretching band is
      observed at about q = (0.2,0,0). These signatures provide evidence for strong
      electron-phonon coupling in this electron-doped high-temperature superconductor.

PMID- 11955250
TI  - Intrinsic behavior of flux lines in pure niobium near the upper critical field.
AB  - We report small-angle neutron-scattering (SANS) measurements of flux line
      properties near H(c2) in an ultrapure sample of niobium with weak pinning of flux
      in the bulk. These confirm in detail the Abrikosov picture of the flux line
      lattice to within 20 mK of the upper critical field line. However, it has
      recently been claimed [X. S. Ling et al., Phys. Rev. Lett. 86, 712 (2001)], on
      the basis of SANS observations of a disordering of flux lines in niobium, that
      the flux lattice melts at temperatures clearly separated from the upper critical
      field line. This discrepancy may possibly arise from differences in sample purity
      and pinning.

PMID- 11955251
TI  - Temperature and field dependence of the anisotropy of MgB2.
AB  - The anisotropy gamma of the superconducting state of high quality single crystals
      of MgB2 was determined, using torque magnetometry with two different methods. The
      anisotropy of the upper critical field was found to be temperature dependent,
      decreasing from gamma approximately 6 at 15 K to 2.8 at 35 K. Reversible torque
      data near T(c) reveal a field dependent anisotropy, increasing nearly linearly
      from gamma approximately equal to 2 in zero field to 3.7 in 10 kOe. The unusual
      temperature dependence is a true bulk property and can be explained by nonlocal
      effects of anisotropic pairing and/or the k--> dependence of the effective mass
      tensor.

PMID- 11955252
TI  - Magnetoresistance of untwinned YBa(2)Cu(3)O(y) single crystals in a wide range of
      doping: anomalous hole-doping dependence of the coherence length.
AB  - Magnetoresistance (MR) in the a-axis resistivity of untwinned YBa(2)Cu(3)O(y)
      single crystals is measured for a wide range of doping ( y = 6.45-7.0). The y
      dependence of the in-plane coherence length xi(ab) estimated from the fluctuation
      magnetoconductance indicates that the superconductivity is anomalously weakened
      in the 60-K phase; this observation, together with the Hall coefficient and the a
      axis thermopower data which suggest the hole doping to be 12% for y approximately
      equal to 6.65, gives evidence that the origin of the 60-K plateau is the 1/8
      anomaly. At high temperatures, the normal-state MR data show signatures of the
      Zeeman effect on the pseudogap in underdoped samples.

PMID- 11955253
TI  - Quasiparticle liquid in the highly overdoped Bi(2)Sr(2)CaCu(2)O(8+delta).
AB  - Results from the study of a highly overdoped (OD) Bi(2)Sr(2)CaCu(2)O(8+delta)
      with a T(c) = 51 K using angle-resolved photoemission spectroscopy are presented.
      We observe a sharp peak in the spectra near ( pi,0) that persists well above
      T(c), a nodal self-energy which approaches that seen for the Mo(110) surface
      state, and a more k-independent line shape at the Fermi surface than the lower
      doped cuprates. This allows for a realistic comparison of the lifetime values to
      the experimental resistivity measurements. These observations point to the
      validity of the quasiparticle picture for the OD even in the normal state.

PMID- 11955254
TI  - Kink pairs unbinding on domain walls and the sequence of phase transitions in
      fully frustrated XY models.
AB  - The unbinding of kink pairs on domain walls in the fully frustrated XY model (on
      square or triangular lattices) is shown to induce the vanishing of phase coupling
      across the walls. This forces the phase transition, associated with unbinding of
      vortex pairs, to take place at a lower temperature than the other phase
      transition, associated with proliferation of the Ising-type domain walls. The
      results are applicable for a description of superconducting junction arrays and
      wire networks in a perpendicular magnetic field, as well as of planar
      antiferromagnets with a triangular lattice.

PMID- 11955255
TI  - Competition between charge- and spin-density-wave order and superconductivity in
      La(1.875)Ba(0.125-x)Sr(x)CuO(4).
AB  - We have performed a series of elastic neutron scattering measurements on 1/8-hole
      doped La(1.875)-Ba(0.125-x)Sr(x)CuO(4) single crystals with x = 0.05, 0.06,
      0.075, and 0.085. Both charge-density-wave (CDW) and spin-density-wave orders are
      found to develop simultaneously below the structural transition temperature
      between the low-temperature orthorhombic (LTO) and low-temperature tetragonal
      (LTT) or low-temperature less-orthorhombic (LTLO) phases. In the ground state the
      CDW order is observed only in the LTT/LTLO phase and drastically degrades towards
      the LTO boundary. The x dependence of T(c) strongly suggests a direct effect of
      the CDW order on the suppression of superconductivity.

PMID- 11955256
TI  - Observation of magnetic level repulsion in Fe6:Li molecular antiferromagnetic
      rings.
AB  - Heat capacity (C), magnetic torque, and proton NMR relaxation rate (1/T(1))
      measurements were performed on Fe6:Li single crystals in order to study the
      crossings between S = 0 and S = 1 and between S = 1 and S = 2 magnetic states of
      the molecular rings, at magnetic fields B(c1) = 11.7 T and B(c2) = 22.4 T,
      respectively. C vs B data at 0.78 K show that the energy gap between two states
      remains finite at B(c)'s (Delta(1)/k(B) = 0.86 K and Delta(2)/k(B) = 2.36 K) thus
      proving that levels repel each other. The large Delta(1) value may also explain
      the anomalously large width of the peak in 1/T(1) vs B, around B(c1). This
      anticrossing, unexpected in a centrosymmetric system, requires a revision of the
      Hamiltonian.

PMID- 11955257
TI  - Strongly enhanced magnetic moments of vanadium impurities in thin films of sodium
      and potassium.
AB  - Thin quench-condensed films of Na and K are covered with 1/100 of a monolayer of
      V. Then the impurities are covered with several atomic layers of the host. The
      magnetization of the films is measured by means of the anomalous Hall effect. For
      V impurities on the surface of Na and K, a magnetic moment of 7 Bohr magnetons is
      observed. After coverage with the host, the V moment became 6.5 mu(B) for the Na
      host. These results contradict the favored atomic model (predicting 3/5 mu(B))
      and the resonance model. A polarization of the alkali host appears to be the only
      resolution.

PMID- 11955258
TI  - Spinons in a crossed-chains model of a 2D spin liquid.
AB  - Using the random phase approximation, we show that a crossed-chains model of spin
      1/2 Heisenberg chains with frustrated interchain couplings has a nondimerized
      spin-liquid ground state in 2D, with deconfined spinons as the elementary
      excitations. The results are confirmed by a bosonization study, which shows that
      the system is an example of a "sliding Luttinger liquid." In an external field,
      the system develops an incommensurate field-induced long-range order with a
      finite transition temperature.

PMID- 11955259
TI  - Charge ordering fluctuation and optical pseudogap in La(1-x)Ca(x)MnO(3).
AB  - Optical spectroscopy was used to investigate the optical gap ( 2 Delta) due to
      charge ordering (CO) and related pseudogap developments with x and temperature (
      T) in La(1-x)Ca(x)MnO(3) ( 0.48< or =x< or =0.67). Surprisingly, we found 2
      Delta/k(B)T(CO) is as large as 30 for x approximately 0.5, and decreases rapidly
      with increasing x. Simultaneously, the optical pseudogap, possibly starting from
      T* far above T(CO) becomes drastically enhanced near x = 0.5, producing non-BCS T
      dependence of 2 Delta with the large magnitude far above T(CO), and systematic
      increase of T* for x approximately 0.5. These results unequivocally indicate
      systematically enhanced CO correlation when x approaches 0.5 even though T(CO)
      decreases.

PMID- 11955260
TI  - Finite temperature magnetism in Gd: evidence against a Stoner behavior.
AB  - The temperature dependence of the rare-earth valence bands has been regarded as a
      realization of the Stoner behavior. The exchange splitting of the electronic
      states appears to scale as the magnetic order parameter for T<T(C) and to vanish
      at T = T(C). We report here a spin-resolved photoemission study on the evolution
      of Gd bulk bands for 0.5< or =T/T(C)< or=1. The spin-polarized spectral line
      shapes display a complex temperature dependence, which clearly contrasts with the
      interpretation of previous experimental results. The spin-resolved photoemission
      data demonstrate the inadequacy of the Stoner model to the description of
      magnetism in rare earths.

PMID- 11955261
TI  - T(3/2) dependence of the interlayer exchange coupling in ferromagnetic
      multilayers.
AB  - The temperature dependence of the interlayer exchange coupling in ferromagnetic
      films coupled across nonmagnetic spacers is determined via in situ ferromagnetic
      resonance experiments for various systems. Clear evidence for a T(3/2) law is
      found over a wide temperature regime.

PMID- 11955262
TI  - Macroscopic magnetization jumps due to independent magnons in frustrated quantum
      spin lattices.
AB  - For a class of frustrated spin lattices including the Kagome lattice we construct
      exact eigenstates consisting of several independent, localized one-magnon states
      and argue that they are ground states for high magnetic fields. If the maximal
      number of local magnons scales with the number of spins in the system, which is
      the case for the Kagome lattice, the effect persists in the thermodynamic limit
      and gives rise to a macroscopic jump in the zero-temperature magnetization curve
      just below the saturation field. The effect decreases with increasing spin
      quantum number and vanishes in the classical limit. Thus it is a true macroscopic
      quantum effect.

PMID- 11955263
TI  - Finite-temperature phase diagram of hard-core bosons in two dimensions.
AB  - We determine the finite-temperature phase diagram of the square lattice hard-core
      boson Hubbard model with nearest neighbor repulsion using quantum Monte Carlo
      simulations. This model is equivalent to an anisotropic spin-1/2 XXZ model in a
      magnetic field. We present the rich phase diagram with a first order transition
      between a solid and superfluid phase, instead of a previously conjectured
      supersolid and a tricritical end point to phase separation. Unusual reentrant
      behavior with ordering upon increasing the temperature is found, similar to the
      Pomeranchuk effect in 3He.

PMID- 11955264
TI  - Anomalous quantum-confined Stark effects in stacked InAs/GaAs self-assembled
      quantum dots.
AB  - Vertically stacked and coupled InAs/GaAs self-assembled quantum dots (SADs) are
      predicted to exhibit strong hole localization even with vanishing separation
      between the dots, and a nonparabolic dependence of the interband transition
      energy on the electric field, which is not encountered in single SAD structures.
      Our study based on an eight-band strain-dependent k x p Hamiltonian indicates
      that this anomalous quantum confined Stark effect is caused by the three
      dimensional strain field distribution which influences drastically the hole
      states in the stacked SAD structures.

PMID- 11955265
TI  - Local realistic model for the dynamics of bulk-ensemble NMR information
      processing.
AB  - We construct a local realistic hidden-variable model that describes the states
      and dynamics of bulk-ensemble NMR information processing up to about 12 nuclear
      spins. The existence of such a model rules out violation of any Bell inequality,
      temporal or otherwise, in present high-temperature, liquid-state NMR experiments.
      The model does not provide an efficient description in that the number of hidden
      variables grows exponentially with the number of nuclear spins.

PMID- 11955266
TI  - Quantum key distribution with bright entangled beams.
AB  - We suggest a quantum cryptographic scheme using continuous EPR-like correlations
      of bright optical beams. For binary key encoding, the continuous information is
      discretized in a novel way by associating a respective measurement, amplitude, or
      phase, with a bit value "1" or "0." The secure key distribution is guaranteed by
      the quantum correlations. No predetermined information is sent through the
      quantum channel contributing to the security of the system.

PMID- 11955267
TI  - Catalysis in nonlocal quantum operations.
AB  - We show how entanglement can be used, without being consumed, to accomplish
      unitary operations that could not be performed without it. When applied to
      infinitesimal transformations, our method makes equivalent, in the sense of
      Hamiltonian simulation, a whole class of otherwise inequivalent two-qubit
      interactions. The new catalysis effect also implies the asymptotic equivalence of
      all such interactions.

PMID- 11955268
TI  - Specific and nonspecific collapse in protein folding funnels.
AB  - Experiments with fast folding proteins are beginning to address the relationship
      between collapse and folding. We investigate how different scenarios for folding
      can arise depending on whether the folding and collapse transitions are
      concurrent or whether a nonspecific collapse precedes folding. Many earlier
      studies have focused on the limit in which collapse is fast compared to the
      folding time; in this work we focus on the opposite limit where, at the folding
      temperature, collapse and folding occur simultaneously. Real proteins exist in
      both of these limits. The folding mechanism varies substantially in these two
      regimes. In the regime of concurrent folding and collapse, nonspecific collapse
      now occurs at a temperature below the folding temperature (but slightly above the
      glass transition temperature).

PMID- 11955269
TI  - Viscosity of two-dimensional suspensions.
AB  - Over a range of conditions, lipid and surfactant monolayers exhibit coexistence
      of discrete solid domains in a continuous liquid. The surface shear viscosity,
      mu(s), of such monolayers collapses onto a single curve: mu(s)/mu(so) = [1
      (A/A(c))](-1), in which mu(so) is the viscosity of the liquid phase, A is the
      area fraction of the solid phase measured by fluorescence microscopy, and A(c) is
      a critical solid phase fraction. This scaling relationship is directly analogous
      to that of three-dimensional dispersion of spheres in a solvent with long-range
      repulsive interactions, with area fraction replacing volume fraction.

PMID- 11955270
TI  - Rectified motion of colloids in asymmetrically structured channels.
AB  - We set micron size particles into macroscopic motion by submitting them to a low
      frequency electric field (of zero mean value) in a microfabricated channel
      exhibiting a topological ratchet-like local polarity. Rectification is induced by
      the coupling between electrophoresis, electroosmosis, and dielectrophoresis. The
      macroscopic velocities of the particles are functions of the electric field and
      of the geometry of the channel; they strongly depend on their size which opens
      the way to potential separations.

PMID- 11955271
TI  - Comment on "Nonclassical smoothening of nanoscale surface corrugations".

PMID- 11955273
TI  - Immune monitoring of cancer biotherapy: need for harmonising biotechnical
      prowess, practicality, and quality control.

PMID- 11955274
TI  - Redirecting cytotoxic T lymphocyte responses with T-cell receptor transgenes.
AB  - In cancer and viral diseases, a great deal of research has focused on generating
      T-cell responses that might prove therapeutic. These efforts stem from our
      understanding of the immune system. It is known that the natural immune response
      can protect or suppress some viral infections and it is hoped that a potent T
      cell mediated immune response might also be harnessed to fight cancer.
      Immunotherapy is a particularly attractive candidate therapy for the treatment of
      metastatic cancer because of the immune systems capacity for body wide
      surveillance. Since the generation of T cell clones is a laborious task and it is
      often impossible to derive T cell clones of the desired specificity and function
      from many individuals, especially in a timely fashion required for therapeutic
      interventions, T-cell receptor (TCR) gene transfer has a lot of appeal. TCR gene
      transfer seeks to transfer the antigen specificity of a T cell clone to other T
      cells. This article will review the last 15 years of research in TCR gene
      transfer since the first successful TCR gene transfer experiment, and seeks to
      give an insight into the areas of investigation currently being pursued to
      improve on current results and move TCR gene transfer into the clinic.

PMID- 11955275
TI  - The potential of ovarian tissue transplant to preserve fertility.
AB  - Laboratory research on ovarian cryopreservation and transplantation began in the
      1950s leading to clinical studies in the 2000s. The research that was performed
      during this half a century indicated that cryopreserved ovarian tissue has the
      potential to restore fertility in women who face premature ovarian failure due to
      chemotherapy, radiotherapy or surgery. Until today, ovarian function has been
      restored in at least four women. Even though no pregnancies have been reported to
      date from these clinical studies, animal studies indicate that this is a valid
      prospect for humans. Future clinical trials will determine in a larger number of
      patients the longevity of ovarian grafts, normalcy of hormone production and
      ovarian follicle development, possibility and safety of pregnancy and the safety
      of auto-transplantation in cancer patients. In addition, further basic research
      may be needed to develop better cryoprotectants and cryopreservation techniques.
      However, the major improvement in the efficiency of ovarian transplantation is
      anticipated to come from research exploring the revascularisation process.

PMID- 11955276
TI  - The significance of immunohistochemistry in the diagnosis and therapy of
      neoplasms.
AB  - This review article details the diagnostical significance of
      immunohistochemistry, which has developed during the last quarter of the century.
      Certainly, the advancement of monoclonal antibody technology has been of great
      significance in assuring the place of immunohistochemistry in the modern accurate
      microscopic diagnosis of human neoplasms, as a method of choice in
      histopathology. The fact still remains that in order to properly assess any
      immunohistochemical reactivity used for differential diagnostic purposes, the
      target cells have to be identified as neoplastically transformed cells by routine
      histopathological techniques. Selected groups of target molecules of great
      significance in cancer biology are discussed. The discovery of neoplasm
      associated antigens has not only made the more accurate diagnosis of human cancer
      feasible but has also shed light on the extensive immunophenotypical
      heterogeneity of even the most closely linked human malignancies. The
      identification of disseminated neoplastically transformed cells by
      immunohistochemistry has allowed for a clearer picture of cancer invasion and
      metastasis, as well as the evolution of the tumour cell associated
      immunophenotype towards increased malignancy. Some possibilities of neoplasm
      associated antigen targeted, receptor-directed immunotherapy are discussed and
      reviewed in this manuscript. Future antineoplastic therapeutical approaches
      should see the inclusion of a variety of immunotherapies, in the form of an
      individualised 'cocktail' specific for the particular immunophenotypical pattern
      associated with each individual patient's neoplastic disease.

PMID- 11955277
TI  - Prostate-specific antigen vaccines for prostate cancer.
AB  - Prostate cancer is the most common malignant tumour in men and there are few
      treatment options available once the tumour becomes refractory to hormonal
      manipulation. Prostate-specific antigen (PSA) is a secretory glycoprotein that is
      commonly expressed by prostatic epithelial cells and is found in elevated levels
      in the serum of men with prostate cancer. The identification of T cell specific
      epitopes within the coding sequence of PSA has led to the development of various
      vaccine strategies that target PSA in an attempt to treat established prostate
      cancer. These strategies have included human leukocyte antigen-restricted PSA
      peptides, dendritic cells pulsed with PSA, recombinant viruses expressing PSA and
      combinations of different vectors. In addition to PSA, several other antigens
      have been described that may be useful for targeting prostate tumours by
      vaccines. Animal studies have established the feasibility and safety for many of
      these agents and clinical trials are now in progress to evaluate the
      immunological and clinical responses of PSA vaccines. Further research in
      manipulating anti-PSA immunity with cytokines, costimulatory molecules and other
      immune modulating agents will likely improve the therapeutic effectiveness of PSA
      vaccines. Clinical trials designed to evaluate the effects of vaccination in
      different stages of disease and through different routes of administration need
      to be performed to define the optimal schedule for PSA vaccines in patients with
      prostate cancer, or for those at high risk of developing the disease.

PMID- 11955278
TI  - Immunotherapy of ovarian cancer.
AB  - Epithelial ovarian cancer remains the leading cause of death due to
      gynaecological malignancy. Although patients with advanced ovarian cancer have a
      good response to surgery and platinum-based chemotherapy, long-term survival
      remains poor. Immunotherapy techniques currently under investigation for
      treatment of recurrence include antitumour monoclonal and bispecific antibodies.
      Antibodies to ovarian cancer antigens have also been combined with radioisotopes,
      immunotoxins and chemotherapeutic drug conjugates to provide improved targeting
      of these agents. Anti-idiotypic antibodies and vaccines have also been developed
      to initiate humoral and cellular immune responses against ovarian cancer.
      Cytokines have been administered alone as well as in combination with other
      immunotherapy agents in patients with ovarian cancer. Finally, antigen-presenting
      cells are being modified by a variety of methods to stimulate an antitumour
      immune response. This review summarises the latest published clinical data and
      highlights promising areas of research in this exciting field.

PMID- 11955279
TI  - Immunotherapeutic approaches to paraneoplastic neurological disorders.
AB  - The review presents an overview on the pathogenesis of paraneoplastic
      neurological disorders (PNDs) and the current therapeutic immunosuppressive or
      immunomodulatory strategies used in these patients. PNDs are disturbances in the
      functioning of the nervous system in cancer patients, where the disturbances are
      not due to a local effect of the tumour or its metastases. Most of these
      clinically, well-defined syndromes in adults are associated with lung cancer
      (especially small cell lung cancer), lymphomas and gynaecological tumours. Since
      autoantibodies directed against proteins expressed in neurons and tumour cells
      have been found, PNDs are suspected to be autoimmune. In neuromuscular PND,
      immunosuppressive therapies, plasmapheresis and intravenous immunoglobulins are
      effective treatments. In contrast, central nervous system PNDs seen in adults are
      by far the most problematic group to treat. With exception of the stiff-man
      syndrome, immunosuppression appears to have little effect on these neurological
      disorders. Tumour therapy stabilises PNDs but does not cause improvement.
      Plasmapheresis reduces the autoantibody titre in the sera of these patients but,
      like tumour therapy, does not lead to a clinical improvement. In children with
      paraneoplastic opsoclonus-myoclonus syndrome, steroids and intravenous
      immunoglobulins may lead to a complete or partial remission of PNDs.

PMID- 11955280
TI  - Selective targeting of T cell subsets: focus on alefacept - a remittive therapy
      for psoriasis.
AB  - Psoriasis is an immune-mediated disease in which memory-effector (CD45RO+), skin
      homing T cells play a key role in driving the disease process. Available
      therapies are often poorly tolerated, none are curative and most only suppress
      disease symptoms without attacking the underlying cause of the illness. Alefacept
      (Ameviv, Biogen, Inc.) is a fully human lymphocyte function associated antigen
      3/immunoglobulin G1 fusion protein that targets memory-effector T cells by
      binding CD2 on the T cell and Fc phi receptor III IgG receptors on accessory
      cells, thereby preventing T cell activation and proliferation and causing
      selective T cell apoptosis. To date, alefacept has been studied in moderate-to
      severe chronic plaque psoriasis and in a pilot study of psoriatic arthritis. In
      chronic plaque psoriasis, alefacept produced significant and sustained
      improvements in psoriasis symptoms. There was no evidence of disease rebound or
      worsening of psoriasis following treatment cessation. Multiple courses provided
      consistent efficacy, with a trend for more rapid and greater clinical improvement
      in subsequent courses. Alefacept reduced circulating CD4+ and CD8+ memory
      effector T cells, with relatively no change in naive (CD45RA+) T cells or B
      cells. Alefacept also reduced IFN-phi-secreting Tcells in lesional biopsies of
      psoriatic skin. These reductions all correlated with the observed clinical
      effect. Alefacept was well-tolerated throughout these studies, with a side effect
      profile similar to placebo. There was no evidence of generalised
      immunosuppression or increased risk of infection or malignancy. Alefacept did not
      alter the primary or acquired immune response in psoriatic patients. Clinical
      data obtained to date support the use of alefacept as a safe and remittive
      therapy for psoriasis.

PMID- 11955281
TI  - 10th International Conference on gene therapy of cancer: 13 - 15 December 2001,
      San Diego, CA, USA.
AB  - This annual meeting was organised by R Sobol and A Deisseroth (Sidney Kimmel
      Cancer Center, San Diego, CA, USA) and K Scanlon (Keck Graduate Institute,
      Claremont, CA, USA). The meeting covered a wide range of topics in cancer gene
      therapy and included five sessions. The topics were: (1) Tumour
      suppressors/apoptosis/antisense-ribozymes/angiogenesis; (2) Vector systems; (3)
      Therapy sensitisation/'suicide' gene therapy; (4) Haematopoietic gene transfer;
      and (5) Poster/discussion sessions. The following meeting highlights have focused
      mainly on the recent progress in antisense/ribozyme-based approaches useful for
      cancer gene target validation and drug development.

PMID- 11955282
TI  - Support for a three-dimensional structure predicting a Cys-Glu-Lys catalytic
      triad for Pseudomonas aeruginosa amidase comes from site-directed mutagenesis and
      mutations altering substrate specificity.
AB  - The aliphatic amidase from Pseudomonas aeruginosa belongs to the nitrilase
      superfamily, and Cys(166) is the nucleophile of the catalytic mechanism. A model
      of amidase was built by comparative modelling using the crystal structure of the
      worm nitrilase-fragile histidine triad fusion protein (NitFhit; Protein Data Bank
      accession number 1EMS) as a template. The amidase model predicted a catalytic
      triad (Cys-Glu-Lys) situated at the bottom of a pocket and identical with the
      presumptive catalytic triad of NitFhit. Three-dimensional models for other
      amidases belonging to the nitrilase superfamily also predicted Cys-Glu-Lys
      catalytic triads. Support for the structure for the P. aeruginosa amidase came
      from site-direct mutagenesis and from the locations of amino acid residues that
      altered substrate specificity or binding when mutated.

PMID- 11955283
TI  - Aerobic sn-glycerol-3-phosphate dehydrogenase from Escherichia coli binds to the
      cytoplasmic membrane through an amphipathic alpha-helix.
AB  - sn-Glycerol-3-phosphate dehydrogenase (GlpD) from Escherichia coli is a
      peripheral membrane enzyme involved in respiratory electron transfer. For it to
      display its enzymic activity, binding to the inner membrane is required. The way
      the enzyme interacts with the membrane and how this controls activity has not
      been elucidated. In the present study we provide evidence for direct protein
      lipid interaction. Using the monolayer technique, we observed insertion of GlpD
      into lipid monolayers with a clear preference for anionic phospholipids. GlpD
      variants with point mutations in their predicted amphipathic helices showed a
      decreased ability to penetrate anionic phospholipid monolayers. From these data
      we propose that membrane binding of GlpD occurs by insertion of an amphipathic
      helix into the acyl-chain region of lipids mediated by negatively charged
      phospholipids.

PMID- 11955284
TI  - D-Lactate transport and metabolism in rat liver mitochondria.
AB  - In the present study we investigated whether isolated rat liver mitochondria can
      take up and metabolize D-lactate. We found the following: (1) externally added D
      lactate causes oxygen uptake by mitochondria [P/O ratio (the ratio of mol of ATP
      synthesized to mol of oxygen atoms reduced to water during oxidative
      phosphorylation)=2] and membrane potential (Delta(psi)) generation in processes
      that are rotenone-insensitive, but inhibited by antimycin A and cyanide, and
      proton release from coupled mitochondria inhibited by alpha-cyanocinnamate, but
      not by phenylsuccinate; (2) the activity of the putative flavoprotein (D-lactate
      dehydrogenase) was detected in inside-out submitochondrial particles, but not in
      mitochondria and mitoplasts, as it is localized in the matrix phase of the
      mitochondrial inner membrane; (3) three novel separate translocators exist to
      mediate D-lactate traffic across the mitochondrial inner membrane: the D
      lactate/H(+) symporter, which was investigated by measuring fluorimetrically the
      rate of endogenous flavin reduction, the D-lactate/oxoacid antiporter (which
      mediates both the D-lactate/pyruvate and D-lactate/oxaloacetate exchanges) and D
      lactate/malate antiporter studied by monitoring photometrically the appearance of
      the D-lactate counteranions outside mitochondria. The D-lactate translocators, in
      the light of their different inhibition profiles separate from the
      monocarboxylate carrier, were found to differ from each other in the V(max)
      values and in the inhibition and pH profiles and were shown to regulate
      mitochondrial D-lactate metabolism in vitro. The D-lactate translocators and the
      D-lactate dehydrogenase could account for the removal of the toxic methylglyoxal
      from cytosol, as well as for D-lactate-dependent gluconeogenesis.

PMID- 11955285
TI  - Localization and function of a calmodulin-apocalmodulin-binding domain in the N
      terminal part of the type 1 inositol 1,4,5-trisphosphate receptor.
AB  - Calmodulin (CaM) is a ubiquitous protein that plays a critical role in regulating
      cellular functions by altering the activity of a large number of proteins,
      including the d-myo-inositol 1,4,5-trisphosphate (IP3) receptor (IP3R). CaM
      inhibits IP3 binding in both the presence and absence of Ca2+ and IP3-induced
      Ca2+ release in the presence of Ca2+. We have now mapped and characterized a Ca2+
      independent CaM-binding site in the N-terminal part of the type 1 IP3R (IP3R1).
      This site could be responsible for the inhibitory effects of CaM on IP3 binding.
      We therefore expressed the N-terminal 581 amino acids of IP3R1 as a His-tagged
      recombinant protein, containing the functional IP3-binding pocket. We showed that
      CaM, both in the presence and absence of Ca2+, inhibited IP3 binding to this
      recombinant protein with an IC50 of approx. 2 microM. Deletion of the N-terminal
      225 amino acids completely abolished the effects of both Ca2+ and CaM on IP3
      binding. We mapped the Ca2+-independent CaM-binding site to a recombinant
      glutathione S-transferase fusion protein containing the first 159 amino acids of
      IP3R1 and then made different synthetic peptides overlapping this region. We
      demonstrated that two synthetic peptides matching amino acids 49-81 and 106-128
      bound CaM independently of Ca2+ and could reverse the inhibition of IP3 binding
      caused by CaM. This suggests that these sequences are components of a
      discontinuous Ca2+-independent CaM-binding domain, which is probably involved in
      the inhibition of IP3 binding by CaM.

PMID- 11955288
TI  - Analysis of a human brain transcriptome map.
AB  - BACKGROUND: Genome wide transcriptome maps can provide tools to identify
      candidate genes that are over-expressed or silenced in certain disease tissue and
      increase our understanding of the structure and organization of the genome.
      Expressed Sequence Tags (ESTs) from the public dbEST and proprietary Incyte
      LifeSeq databases were used to derive a transcript map in conjunction with the
      working draft assembly of the human genome sequence. RESULTS: Examination of ESTs
      derived from brain tissues (excluding brain tumor tissues) suggests that these
      genes are distributed on chromosomes in a non-random fashion. Some regions on the
      genome are dense with brain-enriched genes while some regions lack brain-enriched
      genes, suggesting a significant correlation between distribution of genes along
      the chromosome and tissue type. ESTs from brain tumor tissues have also been
      mapped to the human genome working draft. We reveal that some regions enriched in
      brain genes show a significant decrease in gene expression in brain tumors, and,
      conversely that some regions lacking in brain genes show an increased level of
      gene expression in brain tumors. CONCLUSIONS: This report demonstrates a novel
      approach for tissue specific transcriptome mapping using EST-based quantitative
      assessment.

PMID- 11955286
TI  - Interactions defining the specificity between fungal xylanases and the xylanase
      inhibiting protein XIP-I from wheat.
AB  - We previously reported on the xylanase-inhibiting protein I (XIP-I) from wheat
      [McLauchlan, Garcia-Conesa, Williamson, Roza, Ravestein and Maat (1999), Biochem.
      J. 338, 441-446]. In the present study, we show that XIP-I inhibits family-10 and
      -11 fungal xylanases. The K(i) values for fungal xylanases ranged from 3.4 to 610
      nM, but bacterial family-10 and -11 xylanases were not inhibited. Unlike many
      glycosidase inhibitors, XIP-I was not a slow-binding inhibitor of the Aspergillus
      niger xylanase. Isothermal titration calorimetry of the XIP-I-A. niger xylanase
      complex showed the formation of a stoichiometric (1:1) complex with a heat
      capacity change of -1.38 kJ x mol(-1) x K(-1), leading to a predicted buried
      surface area of approx. 2200+/-500 A(2) at the complex interface. For this
      complex with A. niger xylanase (K(i)=320 nM at pH 5.5), titration curves
      indicated that an observable interaction occurred at pH 4-7, and this was
      consistent with the pH profile of inhibition of activity. In contrast, the
      stronger complex between A. nidulans xylanase and XIP-I (K(i)=9 nM) led to an
      observable interaction across the entire pH range tested (3-9). Using surface
      plasmon resonance, we show that the differences in the binding affinity of XIP-I
      for A. niger and A. nidulans xylanase are due to a 200-fold lower dissociation
      rate k(off) for the latter, with only a small difference in association rate
      k(on).

PMID- 11955289
TI  - Is primary care ready to take on Attention Deficit Hyperactivity Disorder?
AB  - BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood
      psychiatric disorder. The management of ADHD has recently been highlighted. The
      National Institute of Clinical Excellence (NICE) and Scottish Intercollegiate
      Guidelines network (SIGN) have both produced management guidelines. Doctors
      working within Primary Care in countries such as the United States play an
      important role in the management of ADHD. In the United Kingdom however the role
      of doctors in primary care in the management of ADHD, both individually and
      within shared care protocols, is only now being identified and defined. Is this
      role for Primary Care likely to be acceptable and effective? DISCUSSION: There is
      some evidence that doctors working within Primary Care in the United Kingdom are
      willing to follow up children on medication for ADHD and carry out monitoring of
      physical status. However many feel unconfident in the management of ADHD and most
      have received little or no training in child psychiatry. There are also concerns
      that adverse media reports will have an undue influence on the attitudes of
      doctors within primary care to families with children suffering from ADHD.
      SUMMARY: There are important barriers to be tackled before shared care protocols
      for ADHD can be successfully implemented in the United Kingdom. Tailored
      information about ADHD needs to be provided to doctors in primary care. Clear
      dialogue between planners and healthcare professionals from both primary and
      secondary care is essential to ensure that service delivery is acceptable to
      healthcare providers, tailored to their skills and is adequately resourced.

PMID- 11955291
TI  - Cross-sectional study of morbidity, morbidity-associated factors and cost of
      treatment in Ngaoundere, Cameroon, with implications for health policy in
      developing countries and development assistance policy.
AB  - BACKGROUND: In a population-based epidemiological study in Ngaoundere, Cameroon,
      we studied cross-sectional child morbidity and the cost of necessary
      investigation and treatment. METHODS: Three teams of two to three health workers
      visited haphazardly selected households in all major housing quarters. We asked
      permission to enter for a health survey. Children with cough, fever or weight
      loss as well as sick adults were offered free-of-charge local hospital
      examination and treatment. RESULTS: From 177 households with 1777 persons, 51
      (2.9%) persons were referred. Thirty-five of them had an undiagnosed disease
      threatening individual health and in many cases also public health. Seven were
      hospitalised, including three adults with tuberculosis. Malnutrition was
      diagnosed in nine small children. Four patients had AIDS, seven had malaria.
      Average total cost for ambulant patients was 15 USD, for hospitalised patients
      110 USD.In the households, almost half of the women 16-50 years of age had no
      schooling. Two per cent of women and nine per cent of men were daily smokers.
      Coughing children were more likely than non-coughing children to live in a
      household with at least one smoker (OR = 3.58, 95% CI 1.72 to 7.46), and they
      generally lived in more poor households (P = 0.018). Twelve of 16 children with
      weight loss were referred from households with a high poverty score. CONCLUSIONS:
      Adult smoking and poverty affect children's health. The cost of hospitalisation
      or long-lasting therapy is beyond the means of most ordinary families. Diseases
      with severe consequences for public health, like tuberculosis, AIDS and malaria
      should have national programs with free, decentralised examination and treatment.
      Access to generic drugs is important. A major educational effort is needed to
      improve public health.

PMID- 11955290
TI  - Effects of leucine supplemented diet on intestinal absorption in tumor bearing
      pregnant rats.
AB  - BACKGROUND: It is known that amino acid oxidation is increased in tumor-bearing
      rat muscles and that leucine is an important ketogenic amino acid that provides
      energy to the skeletal muscle. METHODS: To evaluate the effects of a leucine
      supplemented diet on the intestinal absorption alterations produced by Walker
      256, growing pregnant rats were distributed into six groups. Three pregnant
      groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing
      (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet
      supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor
      bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which
      received a normal protein diet, were used as a control group. After 20 days, the
      animals were submitted to intestinal perfusion to measure leucine, methionine and
      glucose absorption. RESULTS: Tumor-bearing pregnant rats showed impairment in
      food intake, body weight gain and muscle protein content, which were less
      accentuated in WL than in WN rats. These metabolic changes led to reduction in
      both fetal and tumor development. Leucine absorption slightly increased in WN
      group. In spite of having a significant decrease in leucine and methionine
      absorption compared to L, the WL group has shown a higher absorption rate of
      methionine than WN group, probably due to the ingestion of the leucine
      supplemented diet inducing this amino acid uptake. Glucose absorption was reduced
      in both tumor-bearing groups. CONCLUSIONS: Leucine supplementation during
      pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the
      availability of the amino acid for neoplasic cells and, mainly, for fetus and
      host utilization. This may have contributed to the better preservation of body
      weight gain, food intake and muscle protein observed in the supplemented rats in
      relation to the non-supplemented ones.

PMID- 11955292
TI  - [The variance of pathogenic organisms of purulent ulcerative keratitis].
AB  - OBJECTIVE: To identify the variance of pathogens of purulent keratitis and their
      resistance patterns to antibiotics. METHODS: From January 1995 to October 2000,
      all patients with suspected infectious corneal ulcer were examined by bacterial,
      fungal and Acanthameoba culture. The results of microorganism-culture were
      compared with those in literature. RESULTS: Of the specimens in 1 430 cases,
      there were 790 cases (55.2%) with positive culture including bacterial isolates
      in 258 cases (18.0%), fungal isolates in 498 cases (34.8%) and parasites in 34
      cases (2.4%). The Staphylococcus aureous and Pseudomonas aeruginosa that had
      markedly declined since 1980s represented 6.2% and 21.7% of bacterial isolates
      respectively. However, the opportunity organism such as Staphylococcus
      epidermidis represented 27.5%, a tendency of gradual increase. The most common
      fungal pathogen was fusarium spp that represented 64.5% of all positive fungal
      cultures, and Aspergillus spp (13.6%) occupied the second place. The resistance
      of the ocular bacteria to fluoroquinolones gradually increased. Although the
      Pseudomonas aeruginosa was resistant to gentamycin in 36.2%, it was almost no
      resistance to tobramycin (3.4%). The fusarium spp was shown to be resistant to a
      number of the anti-fungal agents, but it is sensitive to natamycin. CONCLUSION:
      The survey of pathogens in purulent ulcerative keratitis and their resistance
      patterns to antibiotics helps in clinical treatment.

PMID- 11955293
TI  - [Effect of FK506 eye-drop combined with keratoplasty on recurrent Mooren's
      ulcer].
AB  - OBJECTIVE: To observe the effect of FK506 eye-drop combined with keratoplasty on
      recurrent Mooren's ulcer. METHODS: 9 cases (15 eyes) of recurrent Mooren's ulcer
      were treated with topical FK506 eye-drop combined with keratoplasty. Of the 15
      eyes, two of Mooren's ulcer smaller than half circle of the limbus were treated
      with 0.1% FK506 eye-drop. Among the other 13 eyes of the ulcer larger than half
      the circle of the limbus, 12 eyes were treated with excision of conjunctiva
      combined with lamellar keratoplasty. One eye with a central corneal perforation
      was treated with penetrating keratoplasty. FK506 eye-drop 0.1% was given to the
      13 operated eyes after the re-epithelialization of the cornea. The effect of
      FK506 on recurrent Mooren's ulcer was observed. Measurements of FK506 in
      surgically resected cornea and conjunctiva, and aqueous humor of the operated
      eyes were performed using enzyme immunoassay procedure. Twelve cases of recurrent
      Mooren's ulcer treated with lamellar keratoplasty combined with topical 0.1%
      dexamethasone eye-drop were taken as control. RESULTS: After application of 0.1%
      FK506 eye-drop, concentrations of 30 - 350 ng/g of FK506 were found in the cornea
      and conjunctiva, and no FK506 was measured in the aqueous humor. Nine cases (15
      eyes) of recurrent Mooren's ulcer were all cured and no recurrence was observed
      during the follow-up time of 12 - 17 months. The vision of 5 eyes was improved
      more than 2 lines after the treatment. Seven eyes of Mooren's ulcer in the
      control group recurred. CONCLUSION: 0.1% FK506 eye-drop combined with
      keratoplasty is an effective treatment for recurrent Mooren's ulcer.

PMID- 11955294
TI  - [The contralateral eye in patients with unilateral iridocorneal endothelial
      syndrome].
AB  - OBJECTIVE: To study the clinical characteristics of the contralateral eyes in
      patients with unilateral iridocorneal endothelial syndrome (ICE). METHODS: The
      clinical characteristics were analyzed retrospectively on the contralateral eyes
      in 42 cases of unilateral ICE. Among them, 19 patients (19 eyes) received
      examinations of refraction, intraocular pressure (IOP), slit lamp, gonioscopy and
      ultrasound biomicroscopy. In the 35 cases (35 eyes), the endothelial cell counts
      of the contralateral eyes were compared with age-matched normal controls using t
      test. RESULTS: In the 19 cases of unilateral ICE syndrome, emmetropia or
      hypermetropia were found in 88.9%, IOP higher than 21 mm Hg was present in one
      case, and anterior chamber depth lower than 2.2 mm was in 50.0%. Atrophy or
      dysplasia of iris existed in 3 cases, there were narrowness and/or adhesion of
      anterior chamber angle in 3 cases and pyramidal adhesion under gonioscopy and/or
      ultrasound biomicroscopy examination in 2 cases. One case represented relative
      paracentral scotoma in the visual field examination. Systematic disorders,
      including hepatitis B, diabetes, hyperthyroidism, duodenum ulceration,
      hypertension were found in 31.6%. In the 35 patients who received endothelial
      cell count, the average endothelial cell density of the contralateral eyes was (2
      593.4 +/- 432.7)/mm(2), which was significantly lower than that of the normal
      controls (2 784.9 +/- 280.6)/mm(2) (t = -2.43, P = 0.019). The hexagonality and
      coefficient variation of cell size of ICE patients did not differ from that of
      the normal controls. CONCLUSIONS: The contralateral eye in cases diagnosed as
      unilateral ICE syndrome may be subclinically involved, so it is necessary to pay
      attention to the contralateral eye, and follow up all the patients suffered from
      ICE syndrome.

PMID- 11955295
TI  - [Retrospective analysis of misdiagnosed amoebic keratitis].
AB  - OBJECTIVE: To analyze the clinical characteristic of amoebic keratitis and the
      cause of misdiagnosis retrospectively. METHODS: Corneal pathological sections of
      269 cases having been diagnosed as herpes simplex keratitis (HSK), bacterial
      keratitis and other microbial keratitis and then undergone penetrating
      keratoplasty (PKP) were reexamined to find the misdiagnosed cases of amoebic
      keratitis. The clinical characteristic efficacy of treatment and cause of
      misdiagnosis were retrospectively analyzed according to case history and
      photographs. RESULTS: Based on the pathological examination, 5 cases of amoebic
      keratitis were recognized which had been misdiagnosed, including HSK in 3 cases,
      fungal keratitis in 1 case and suppurative keratitis in 1 case previously. The
      main clinical characteristics were severe radiating neuralgia and ring-shaped
      stromal infiltrates. After PKP, infection of 3 cases were controlled, 2 cases
      were recurrent and underwent eyeball enucleation eventually. CONCLUSION: The
      incidence of amoebic keratitis is not very low in China. It is necessary to pay
      high attention to this kind of disease, and its early and definite diagnosis is
      very important for the prevention of serious results.

PMID- 11955296
TI  - [Experimental and clinical studies on photo-therapeutic keratectomy for
      superficial corneal diseases].
AB  - OBJECTIVE: To study the histologic changes in rabbit corneas after photo
      therapeutic keratectomy (PTK), define the indications and treatment parameters
      and evaluate efficacy of PTK. METHODS: (1) The model of superficial corneal scar
      in rabbit was made by burn with 8.17% sulfuric acid, and then treated with PTK in
      two weeks. The corneas were examined with confocal microscope in vivo, nerve
      staining, light and transmission electron microscope during period after PTK to
      study the histopathologic changes. (2) Thirty eyes with superficial corneal
      diseases including 12 eyes with corneal dystrophy, 2 eyes with band degeneration,
      10 eyes with scar after infection and trauma and 6 eyes with Dimmer nummular
      keratitis were treated with PTK. The method of treatment was varied with
      different diseases. Follow-up was more than six months. To investigate the change
      of haze, visual acuity, refraction and keratometric power during period after
      PTK, chi-square tests were used. RESULTS: (1) Experimental group: in the ablative
      zone at early time after PTK, there were infiltration of polymorphonuclear
      leukocytes accompanied by macrophages, proliferation of fibroblast and loose
      nascent collagen in disorder in the anterior stroma. The wound healing process
      was stable at six months after PTK. (2) Clinical group: compared with the
      preoperative visual acuity, the best corrected visual acuity was improved in 21
      eyes (70.0%), unchanged in 5 eyes (16.7%) and decreased in 4 eyes (13.3%) at six
      months after PTK, and the results were better for corneal dystrophy and band
      degeneration. Haze grade 0.5 was in five eyes, grade I in two eyes and grade 0
      the rest. The mean hyperopic shift was + 1.52 D. CONCLUSIONS: The wound healing
      process in rabbit cornea stabilizes at six months after PTK. PTK is a simple,
      safe, effective treatment for superficial corneal diseases. The indications for
      PTK are corneal pathology in the anterior one-third of the cornea, especially
      corneal dystrophy and band degeneration.

PMID- 11955297
TI  - [Nd: YAG laser clearance of the anterior surface of intraocular lenses].
AB  - OBJECTIVE: To assess the efficacy and safety of Nd: YAG laser in clearing the
      anterior fibrinous membrane of posterior chamber intraocular lens (IOL). METHODS:
      Twenty-four eyes with the anterior fibrinous membrane of posterior chamber IOL
      were treated by Nd: YAG laser with the principle of "Low energy and de-focus"
      from 1997 to 1999 in Peking Union Medical College Hospital. Visual acuity,
      intraocular pressure (IOP) and anterior segment of the eye were followed after
      the laser treatment. RESULTS: Nd: YAG laser successfully cleared the anterior
      fibrinous membrane of IOL and IOLs were not damaged in all 24 eyes. The visual
      acuity was improved in 83.3% of the eyes. The IOP temporarily raised to above 21
      mm Hg in 37.5% of the eyes. Topical steroids were used for the control of the
      intraocular inflammation in anterior segment after laser treatment. CONCLUSION:
      The anterior membrane of IOL can successfully and safely be cleared by Nd: YAG
      laser with the principle of "low energy and de focus".

PMID- 11955298
TI  - [Short-wavelength perimetry in diagnosis of early glaucoma: comparison with
      standard automated perimetry].
AB  - OBJECTIVE: To assess the value of short-wavelength automated perimetry in the
      diagnosis of early glaucoma. METHODS: Fourty-six eyes of 36 patients with early
      open angle glaucoma and a group of 38 normal persons (46 eyes) were examined both
      by the standard automated (white-on-white, W/W) perimeter and short-wavelength
      (blue-on-yellow, B/Y) perimeter. The age and sex in two groups were matched. The
      program 24 - 2 was performed on both B/Y and W/W fields in two groups. The mean
      light sensitivity (MS) of the central 25 degrees and in each quadrant from two
      perimetries was calculated and analyzed statistically by Student t-test and
      ASNOV. RESULTS: The difference of MS in central 25 degrees between two
      perimetries in normal group was 1.63 dB which showed a statistical significance
      of difference (t = 3.57, P < 0.001). MS was significantly higher in W/W than that
      in B/Y either in central 25 degrees or in each corresponding quadrant (t = 3.45,
      P < 0.001). The MS difference between them was more than 2.87 dB and the MS
      average difference of the corresponding quadrant was more than 2.5 dB (t = 4.57,
      3.42, P < 0.001). MS from four quadrants were different from one other. The
      lowest MS was in the superior temporal, the highest MS was in inferior nasal
      quadrant; the superior nasal and inferior temporal were in between them. The
      defects in B/Y perimetry were larger and deeper than that in W/W perimetry. The
      result of corrected deviation points (u = 3.22, P < 0.05) was used to account the
      defected testing points, which showed the defected points were significantly more
      in B/Y perimetry than that in W/W perimetry (chi(2) = 226.72, P < 0.001). The
      data revealed that the defected testing points from B/Y perimetry were 2.6 times
      of that from W/W perimetry. In the early glaucoma group, the positive rate in the
      abnormal visual field from B/Y perimetry was 87% (40/46) and that from W/W
      perimetry, 67% (31/46). CONCLUSIONS: A good coincidence is demonstrated between
      B/Y and W/W perimetries both in normal and in early open angle glaucoma groups.
      B/Y perimetry is more sensitive than W/W perimetry in detecting early
      glaucomatous visual field defects. The positive rate is higher and the defects
      are larger and deeper in B/Y perimetry than that in W/W perimetry. Therefore, B/Y
      perimetry can detect glaucoma defects earlier. It is suggested that B/Y perimetry
      be applied in diagnosing early glaucoma.

PMID- 11955299
TI  - [A comparison of master eye operation with slave eye operation on patients with
      large-angle exotropia].
AB  - OBJECTIVE: To search for an excellent therapy for patients with large-angle
      exotropia. METHODS: Strabotomy was performed on the master eyes in the 41 cases
      (master eye group) and slave eyes in the other 41 cases (slave eye group) with
      large-angle exotropia (>/= 60(Delta)). The post-operative visual acuity, ocular
      position, visual function and fixation, the average surgical amount and the
      frequency of strabotomy were statistically compared between the two groups.
      RESULTS: Post-operatively, orthophoria occurred in 39 cases and mild exotropia
      remained in 2 cases in each group. The statistic analyses showed that the
      surgical results were better in the master eye group in the visual acuity (P <
      0.05), visual function (P < 0.05), average surgical amount and frequency (P <
      0.01). CONCLUSIONS: The surgical results of strabotomy performed on the master
      eye in cases with large-angle exotropia are better than that on the slave eye,
      and the surgical damage in the master eye is less. Thus, the master eye
      strabotomy is especially suitable for children with large-angle exotropia under
      general anesthesia.

PMID- 11955300
TI  - [Orbital volume measurement of enophthalmos of orbital blowout fractures].
AB  - OBJECTIVE: To measure the volumetric changes of enophthalmos of orbital blowout
      fractures, and to study the relation between the change of the orbital volume and
      the degree of enophthalmos. METHODS: In 16 patients with enophthalmos of orbital
      blowout fractures, the measurement of orbital volume was carried out during 3
      months to 2 years after injury by using the computed tomography (CT), computer
      image processing and computer orbital three-dimensional measuring method. The
      relation between the orbital volume discrepancy and enophthalmos was assessed by
      using Pearson correlation coefficients. RESULTS: There were significant linear
      correlation between the increment of the orbital volume and the degree of
      enophthalmos (r = 0.95, P < 0.001), with each 1.0 cm(3) increment in bony volume
      causing approximately 0.9 mm of enophthalmos. CONCLUSIONS: Orbital blowout
      fractures can expand the orbital volume. The measurement of orbital volume may
      predict the risk and the final degree of the enophthalmos at the late stage, thus
      it may provide useful information in surgical intervention to estimate the size
      and volume of the orbital implant for an individual case.

PMID- 11955301
TI  - [Effect of RU38486 on fibronectin expression in cultured human trabecular cells].
AB  - OBJECTIVE: To study the effect of RU38486 on fibronectin expression in human
      trabecular cells (HTCs) in vitro. METHODS: The trabecular specimens from human
      donors were primarily cultured and subcultured. Cultured cells were observed by
      light and electron microscopes. Fibronectin (FN), laminin (LN) and neuron
      specific enolase (NSE) in extracellular matrix (ECM) of the cells were
      immunohistochemically stained with LSAB method. The quantities of FN [optical
      density (A) means] affected by different concentrations of dexamethasone (Dex)
      and RU38486 were measured through indirect immunochemical method associated with
      computer image analysis. RESULTS: According to the growing characteristics and
      morphological features, the cultured cells were identified as HTCs. Comparison of
      A means of FN induced by Dex and RU38486 was 10(-6) mol/L dex (12 days) > 10(-7)
      mol/L Dex (12 d) > 10(-7) mol/L Dex (5 d) > Control group = 10(-7) mol/L Dex (5
      d) + 10(-8) mol/L RU38486 (7 d). CONCLUSION: Dex can stimulate HTCs in vitro to
      secrete more FN. Bit RU38486 can reverse this high level of FN expression induced
      by Dex on receptor level. The efficacy of RU 38486 [glucocorticoid receptor (GR)
      antagonist] in reducing intraocular pressure in vivo should be confirmed by
      further studies.

PMID- 11955302
TI  - [The epithelial-flap abnormality of laser epithelial keratomileusis].
AB  - OBJECTIVE: To investigate the technique of epithelial-flap performance and
      reposition and the factors related to the complication to improve the quality of
      laser epithelial keratomileusis (LASEK). METHODS: Fourteen eyes (9 cases) of
      epithelial-flap abnormality occurring in and after the operation in 309 eyes were
      observed and analyzed. The factors related to the abnormal flap were listed and
      discussed. RESULTS: The abnormal epithelial flaps of LASEK during and after the
      operation were free epithelial-flap, dissolution, fragments, fold, slip, and the
      late epithelial-flap abnormalities including epithelial defect and sub-epithelial
      foreign body 48 - 72 hours postoperatively. The related factors of complication
      included the shallow cut of micro-trephine, improper (too small) cut ring,
      improper concentration of alcohol, the invasion of alcohol solution, dry center
      of epithelial-flap, corneal epithelial injury by irrigation, and too early
      removal of contact lens. CONCLUSION: The epithelial-flap of LASEK is frailer than
      that of LASIK. The key point in the performance of a fine epithelial-flap is to
      manage every procedure carefully.

PMID- 11955303
TI  - [Excimer retreatment for undercorrection or regression after laser in situ
      keratomileusis].
AB  - OBJECTIVE: To evaluate the results of excimer retreatment for undercorrection or
      regression after laser in situ keratomileusis (LASIK). METHODS: Eight-eight eyes
      received retreatment for undercorrection or regression after first LASIK (FLASIK)
      in 2 149 eyes in our photorefractive keratotectomy (PRK)/LASIK center from March,
      1996 to July, 1999. They were divided into 2 groups according to their degrees of
      pre-FLASIK myopia spherical equivalents. Group I was </= 10.00 diopters (D) (41
      eyes); group II was > 10.00 D (47 eyes). We analyzed the factors of FLASIK which
      led to the re-LASIK (RLASIK), and observed the mean spherical equivalents (MSE),
      the ratio within +/- 1.00 D of emmetropia, the uncorrected visual acuity (UCVA),
      the best corrected visual acuity (BCVA) and the complication after RLASIK for at
      least 1 year follow-up study. RESULTS: The retreatment ratio was 4.1% among the 2
      149 eyes. In group II, the ratio was 2.3 times that of the group I. In the
      comparison with other eyes, the eyes received RLAISK had no difference in sex,
      laterality and age (P > 0.05). Over 50.0% had pre-FLASIK diopters >/= 10.00 D,
      and 73.9% had astigmatism correction in FLASIK. After RLASIK, no undercorrection
      or regression occurred in group I, but there was undercorrection in group II. The
      ratio within +/- 1.00 D of emmetropia after 1 year was 68.3% in group I and 51.1%
      in group II. The UCVA above 0.5 was over 90.0% in all eyes. Eight eyes (9.0%)
      lost two or more lines of BCVA. The serious complication after RLASIK was
      keratoconus of 3 eyes in group II. CONCLUSIONS: The risk factors which lead to
      retreatment after FLASIK are high myopia with astigmatism before FLKSIK and the
      reaction to the operation. In this study, RLKSIK is safe, effective, predictable
      and accurate for </= -10.00 D correction in FLASIK. But, to prevent the
      occurrence of serious complication such as keratoconus, it is better not to
      perform RLASIK for > -10.00 D in FLASIK.

PMID- 11955304
TI  - [The early changes of tear film after laser in situ keratomileusis].
AB  - OBJECTIVE: To investigate the early changes of tear film after laser in situ
      keratomileusis (LASIK). METHODS: One hundred and forty-eight myopic eyes that
      underwent LASIK were randomly chosen. The eyes were observed for subjective
      complaints of dry eye, fluorescein staining (Fl), rose bengal staining (Rb), tear
      break-up time (BUT), Schirmer's I test preoperatively and 1 day, 1 week, 1 month,
      3 months postoperatively. RESULTS: The subjective complaints of dry eye were more
      severe after the operation. There were obvious decreases in BUT at 1 day, 1 week,
      1 month and 3 months postoperatively relative to the preoperative level (P <
      0.05). The Schirmer's I test result was higher at 1 day but without statistical
      significance (P > 0.05), but lower at 1 week, 3 months (P < 0.05) after LASIK. No
      changes were observed in Schirmer's I test between preoperative and 1 month
      postoperative value (P > 0.05). Rb and Fl staining dots were more concentrated at
      1 day and 1 week postoperatively (P < 0.0127). No significant changes were found
      in Rb staining at 1 month and 3 months postoperatively. CONCLUSION: LASIK does
      have some effects on tear film.

PMID- 11955305
TI  - [Research on the forecast of intraocular lens power after excimer laser
      keratorefractive operation].
AB  - OBJECTIVE: To study the accuracy of different formulas forecasting intracellular
      lens (IOL) power after excimer laser keratorefractive operation. METHODS: One
      hundred and twenty eyes (60 cases) underwent LASIK surgery. Before and after the
      surgery, the IOL powers were calculated to correct the myopia to emmetropia by
      experiential SRK II formula, theoretical SRK/T formula and Binkhoist II formula
      respectively. Then we calculated the IOL power equal to original lens power by F,
      and analyzed the results before and after surgery by SPSS statistical software.
      RESULTS: 1. The IOL powers were not obviously different by different formulas
      between pre-operative and post-operative results in low myopia (P > 0.05). In
      middle and high myopia there were obvious differences (P < 0.01), the
      postoperative results were smaller than the preoperative ones. 2. The differences
      of equal IOL power by different formulas were highly related to the practical
      corrective refractive values of the surgery. Regression formula: The difference
      of equal IOL power = a + b x the practical corrective refractive value of the
      surgery. (SRK II: a = -l.23, b = 0.72; SRK/T: a = -l.03, b = 0.52; Binkhoist II:
      a = -1.44, b = 0.5). CONCLUSION: The IOL powers forecasted by different formulas
      are smaller in middle and high myopia after excimer laser keratorefractive
      operation than that before the operation, and can be corrected by regression
      formula.

PMID- 11955306
TI  - [Photorefractive keratectomy for treatment of ametropia after vitrectomy for
      retinal reattachment].
AB  - OBJECTIVE: To evaluate the efficacy of photorefractive keratectomy (PRK) for the
      treatment of ametropia after vitrectomy for retinal reattachment. METHODS: PRK
      was used to treat 11 eyes of ametropia after victrectomy for more than seven
      months. The visual acuity, retina and corneal endothelial cell densities were
      investigated in a l2-month follow-up study. RESULT: The postoperative visual
      acuity of all the 11 eyes was equal to or above the best corrected visual acuity
      before the operation. Postoperatively, there was no significant change of the
      corneal endothelial cell densities compared with that before the operation.
      CONCLUSION: PRK for ametropia after vitrectomy is an effective and safe surgery.
      But the indication must be selected appropriately.

PMID- 11955307
TI  - [Vitrectomy for severe Coats' disease].
AB  - OBJECTIVE: To investigate the outcome of vitreoretinal surgery for severe Coats'
      disease. METHODS: From December 1995 to December 1999, trans pars plana
      vitrectomy was performed in 11 patients (11 eyes) diagnosed as Coats' disease.
      Ten of them were complicated with total retinal detachment, and the other one had
      tractional retinal detachment caused by epiretinal proliferation. All these
      patients were followed up from 3 months to 4.5 years. RESULTS: All of the
      patients obtained useful vision except 1 patient whose operation was given up
      because of severe shortening of the retina. Three patients had the visual acuity
      higher than 0.02, and the best vision was 0.2. Obliteration of all abnormal
      vessels and resorption of all exudate was found postoperatively from 1 month to 3
      months. Although the retina had been reattached in 10 patients during the
      operation, re-detachment was found in 4 patients postoperatively. After therapy
      all re-detached retina was reattached. The success rate was 90.9%. CONCLUSIONS:
      Vitrectomy with endolaser or scleral cryotherapy is an ideal therapy for severe
      Coats' disease, although the visual prognosis is still limited. It can preserve
      the limited vision, and prevent the severe complications such as rubeosis iridis,
      glaucoma, and phthisis bulbi.

PMID- 11955308
TI  - [Glaucoma valve devices for refractory glaucoma following vitrectomy].
AB  - OBJECTIVE: To evaluate the surgical effectiveness of glaucoma valve devices for
      refractory glaucoma following vitrectomy surgery. METHODS: Sixteen eyes of 15
      patients suffering from secondary glaucoma following vitrectomy were treated with
      glaucoma valve implantation, all of the eyes were in critical condition, and the
      intraocular pressure failed to control after the silicone oil removal and/or with
      glaucoma medication. Among them, 13 eyes underwent Ahmed valve implantation and 3
      eyes underwent Krupin disk implantation. RESULTS: The mean follow-up was 18.5
      months. The total success rate was 76.9% at 3 months, 70.0% at 6 months and 66.7%
      at one year or longer. The postoperative complications included transient
      hyphema, early postoperative hypotony, choroidal detachment, shallow anterior
      chamber and obstruction of the tube tip. CONCLUSION: The glaucoma valve device is
      a safe and effective method for refractory glaucoma following vitrectomy,
      especially for the patients who have a certain level of visual acuity.

PMID- 11955309
TI  - [Treatment of choroidal melanoma with X-ray knife].
AB  - OBJECTIVE: To detect and analyze the therapeutic effects of X-ray knife for
      treatment of choroidal melanoma with the fixation of the eyeball. METHODS: The
      average size of the tumors in 16 eyes of 16 cases was 11.8 mm x 10.0 mm x 4.5 mm.
      The eyeballs were fixed with four rectus retractable sutures under local
      anesthesia (no use of retrobulbar injection). The superior and inferior rectus
      sutures penetrated the upper and lower lids at the middle part of fornixes, and
      the four sutures were anchored at the positions: above the eyebrow, inferior
      orbital rim, root of nose and lateral orbital rim respectively and deep to the
      fascia. A stereotactic linear accelerator, Vrianc 2100 C, was used for the
      radiosurgery, with an average marginal dose 23.4 Gy. The mean follow-up time was
      18.5 months. RESULTS: The tumors in 7 cases (43.8%) shrinked notably during 6 -
      12 months after therapy. In the postoperative 1 - 2 years, the tumors in 11 eyes
      (68.8%) were decreased in size, among them, in 4 eyes only a flat scar remained
      and in 3 eyes the shrinkage was not significant. Enucleation was performed in 3
      patients because of a little increase in size. The total local control rate was
      81.3%. There were no marked side effects except small hemorrhages in or under the
      retina. Fixations of all eyeballs were very stable, and the orientation of
      radiotherapy was accurate. CONCLUSIONS: The therapeutic effects of choroidal
      melanoma with X-ray knife are quite good, and no significant complications are
      found. There is a higher rate of local control. The fixation of eyeball with four
      rectus sutures penetrating eyelids is very stable and reliable.

PMID- 11955310
TI  - [Analysis of visual prognosis and correlative factors in retinal vein occlusion].
AB  - OBJECTIVE: To investigate the visual prognosis, risk factors, complications and
      the causes of visual deterioration in patients with various types of retinal vein
      occlusion (RVO). METHODS: Nine hundred and forty-four eyes of 913 patients with
      various types of RVO were analyzed. The age range of patients was 15 - 89 years
      (average 52.8 +/- 11.9), and the average follow-up was 20.7 months. The data of
      the patients were studied by SPSS software. RESULTS: (1) RVO was classified into
      central RVO (CRVO) in 406 eyes of 391 cases (43.0%), hemi-RVO (HRVO) in 60 eyes
      of 60 cases (6.4%) and branch RVO (BRVO) in 478 eyes of 462 cases (50.6%). (2)
      They were subdivided into ischemic type in 633 eyes (67.1%) and non-ischemic type
      in 311 eyes (32.9%). (3) The visual prognosis: the average initial visual acuity
      (VA) in CRVO, HRVO and BRVO was 0.36, 0.38 and 0.40 respectively. The average
      final VA was 0.40 in CRVO (P > 0.05), 0.50 in HRVO (P > 0.05) and 0.58 in BRVO (P
      < 0.05). (4) The initial VA and prognosis: there was close relationship between
      initial VA and visual prognosis. If the initial VA >/= 0.5, the final acuity
      maintained >/= 0.5 in 70.6% in CRVO, 75.0% in HRVO and 84.9% in BRVO. The
      patients with initial VA </= 0.l had final VA worse than 0.1 in 66.2% of CRVO,
      35.7% of HRVO and 25.3% of BRVO (P < 0.01). (5) Low vision and the rate of
      blindness in RVO: Among the 205 eyes with low vision (21.7%), there were 27.6%
      with CRVO, 31.7% with HRVO and 17.2% with BRVO (P < 0.01). Among the 160 eyes
      with blindness (16.9%), There were 27.6% with CRVO, 11.7% with HRVO and 8.6% with
      BRVO (P < 0.01). (6) The visual prognostic comparison between ischemic type and
      non-ischemic type: there were 189 of 633 eyes with ischemic type (29.9%) and only
      l6 of 311 eyes with non-ischemic type (5.1%) had low vision. In the ischemic
      type, 157 eyes had blindness (25.1%) and 3 eyes with non-ischemic type (1.0%) had
      blindness (P < 0.01). (7) Risk factors of RVO were hypertension (57.8%),
      arteriosclerosis (67.4%), high blood viscosity (24.6%), diabetes (6.2%) and
      primary glaucoma (1.5%). (8) Complications of RVO: cystoid macular edema (CME)
      46.7%, retinal neovascularization (RNV) 21.5%, vitreous hemorrhage 11.4% and
      neovascular glaucoma (NVG) 9.6% (39/406) in CRVO and 1.7% (1/60) in HRVO. (9) Low
      vision caused by CME was 37.9%, and RNV 29.9%; blindness in CME 19.5% and RNV
      23.0%. In 40 eyes with NVG, the final VA was worse than 0.05 in 38 eyes (95.0%).
      CONCLUSION: The rate of blindness of RVO is high, and the visual prognosis of
      ischemic type is worse. There is close relationship between the level of initial
      VA and visual prognosis. CME, RNV and NVG are important causes of blindness.

PMID- 11955311
TI  - [Influence on human keratocyte proliferation by cationic liposome mediated
      transfer of p21WAF1].
AB  - OBJECTIVE: The aim of this study is to investigate the safety and efficiency of
      transducing human keratocytes with beta-galactosidase gene through cationic
      liposome and evaluate the influence of p21WAF1 gene transduction mediated by
      cationic liposome on proliferation of keratocyte. METHODS: (1) Cationic liposome
      mediated plasmid DNA bearing beta-galactosidase gene was transferred into
      cultured human keratocyte, and transduction efficiency was evaluated by enzymatic
      color reaction using X-gal as a substrate. (2) By immunohistochemistry and MTT,
      the effect of p21WAF1 gene transduction mediated by cationic liposome on cultured
      keratocyte proliferation was evaluated. (3) Cellular viability was detected by
      0.5% trypan blue dye. RESULTS: (1) Lipofectaminetrade mark reagent could mediate
      a foreign gene into a cultured human keratocyte, and the highest transduction
      efficiency was 40.5% when DNA/lipofectamine ratio was 1:8 and the transduction
      time was 24 hr. (2) p21WAF1 gene transduction mediated by lipofectaminetrade mark
      reagent could increase the p21 protein expression in the keratocyte, and inhibit
      the keratocyte proliferation during 2 - 10 days after transduction. And rates of
      cellular viability in all groups were greater than 90% by trypan blue dye
      examination. CONCLUSION: Cationic liposome can mediate foreign gene into cultured
      human keratocytes safely and effectively; p21WAF1 gene transduction mediated by
      cationic liposome can inhibit the proliferation of human keratocyte.

PMID- 11955312
TI  - [Pharmacokinetics of topically applied fluconazole in the rabbit eye].
AB  - OBJECTIVE: To observe the penetration of 0.5% fluconazole (FCZ) into the corneas
      and aqueous humors of New Zealand white rabbits following its topical
      application. METHODS: The rabbit corneas and aqueous humors were obtained and
      quantified at different times after topically applying 0.5% FCZ to the rabbit
      eyes. The drug levels were assayed by high performance liquid chromatography
      (HPLC). The pharmacokinetic parameters were calculated with nonlinear least
      square method by the computer. RESULTS: FCZ can rapidly penetrate into rabbit
      corneas. Peak corneal levels occurred essentially immediately at 2 min in the
      corneas (15.20 +/- 1.95) microgram/g and at 15 min after application in the
      aqueous (2.39 +/- 0.92 mg/L). The permeability of the corneal epithelial barrier
      (Kep) was 1.06 x 10(-5). The half-life (t(l/2)) of the cornea was 63.96 min, and
      that of the aqueous humor was 42.14 min. CONCLUSION: Topical fluconazole can be
      used as a topical antifungal agent to treat keratitis and needs further
      evaluation for treating fungal endophthalmitis.

PMID- 11955313
TI  - [Experimental studies of effects of retinoic acid on the proliferation of retinal
      cells].
AB  - OBJECTIVE: To determine whether the application of exogenous retinoic acid (RA)
      may induce the proliferation of retinal cells in adult rat. METHODS: Thirty-two
      healthy adult Sprague-Dawley (SD) rats were randomly divided into 4 groups. In
      Group 1 and Group 2, all-trans RA (5 microliter, 0.001 mol/L) was injected into
      the subretinal space. In Group 3 and Group 4, all-trans RA (10 microliter, 0.001
      mol/L) was injected into epiretinal vitreous space. In the Group 1 and Group 3,
      transient ischemic-reperfusion injuries of the experimental eyes were induced by
      ligating ophthalmic artery prior to RA treatment. In the control group, 5 SD rats
      were treated by ischemia-reperfusion injuries but no exogenous RA application.
      The treated eyes were enucleated for light microscopic analysis and
      immunohistochemical assays after 2 - 4 weeks of RA application. RESULTS: In group
      1, the number of the retinal cells expressing rod-specific opsin marker in the
      subretinal space was significantly increased and the thickness of inner nuclear
      layer was also increased after the RA treatment for 16 days. However, no cell
      proliferation was detected in group 2. There were also no changes within
      population of retinal cells in Group 3 and Group 4 in which RA was injected into
      epiretinal vitreous space no matter under the ischemia-reperfusion or non
      ischemia-reperfusion. In the control group, there were no significant
      morphological changes within the neural retinal layers as well as photoreceptor
      proliferation. CONCLUSIONS: The application of RA in the subretinal space can
      induce photoreceptor proliferation in adult rat under an ischemic-reperfusion
      injury condition. It will provide a new idea for the regeneration of neural
      retinal cells.

PMID- 11955314
TI  - [Analysis of articles on ocular fundus diseases in Chinese medical journals].
AB  - OBJECTIVE: To find out evidence for the improvement of research resources of
      ocular fundus diseases in China. DATA SOURCES RESEARCH: articles about fundus
      oculi in 418 Chinese medical journals published in the mainland of China from
      January 1, 1999 to June 30, 2001. DATA SELECTION: A total of 2 352 articles about
      ocular fundus diseases included 1 651 original articles, 324 case reports, and
      171 reviews. The original articles covered basic research (402 articles),
      clinical research (530), treatment with combined traditional Chinese and Western
      medicine (270), clinical application of testing technology (295), epidemiology
      (142), and others (12). RESULTS: Data showed that retinal detachment, trauma,
      retinal vein occlusion, and diabetic retinopathy were the major areas of clinical
      research. Ophthalmology periodicals published most of the achievements in the
      research of ocular fundus diseases, while less in general medical journals. Yet,
      reports on critical evaluation of these treatments were not available. The
      resources of research and utilization in ocular fundus diseases in China had not
      been documented. CONCLUSIONS: The research into ocular fundus diseases is an
      active area in China. Critical evaluation and application of the research
      resources of ocular fundus diseases should be improved.

PMID- 11955315
TI  - [Surgical therapeutic results of rhegmatogenous retinal detachment associated
      with choroidal detachment].
AB  - OBJECTIVE: To evaluate the effect of different factors on the prognosis of
      rhegmatogenous retinal detachment (RRD) associated with choroidal detachment
      (ChD). METHODS: One hundred and eighty-eight eyes of 188 patients were studied
      retrospectively from Jan, 1996 to Aug, 1998. The clinical data, surgical
      management and follow-up records were analyzed. RESULTS: The total successful
      rate of the surgery was 83.0%, lower than that of general RRD. In the eyes with
      proliferative vitreoretinopathy (PVR) A-B, the rate was 89.6%, in the eyes with
      C(1)-C(3) PVR, the rate was 84.1%, in D(1)-D(3), 69.0%. In eyes with severe PVR
      the successful rate of vitrectomy was higher than that of scleral buckling alone.
      Administration of steroids before surgery resulted in high successful rate, but
      the length of time of the steroid treatment had no effect on the successful rate.
      In the eyes using scleral buckling alone, the drainage or without the drainage of
      subretinal fluid had no effect on the successful rate. CONCLUSIONS: RRD
      associated with ChD has worse prognosis than general RRD. The administration of
      steroids before surgery is necessary, and the timing of surgery is also
      important. In eyes with light PVR and ChD, scleral buckling without drainage of
      subretinal fluid is the first choice, but in eyes with severe PVR and ChD,
      vitrectomy is a better choice.

PMID- 11955316
TI  - [Application of confocal scanning laser Doppler retinal flowmetry in the
      measurement of fundus blood flow parameters after retinal detachment surgery].
AB  - OBJECTIVE: To discuss the influence of retinal detachment (RD) surgery on the
      blood flow of retina and optic nerve head. METHODS: Heidelberg Retina Flowmeter
      (HRF) was used to measure the blood flow of retina and optic nerve head in 62
      eyes of 62 patients with postoperative rhegmatogenous RD surgery, including 34
      eyes having undertaken vitreoretinal (VR) surgery and 28 eyes, scleral buckling
      (SB) surgery. Operative methods included scleral encircling procedure,
      cryotherapy, lensectomy, vitrectomy, perfluorodeclin liquid application,
      endolaser and C(2)F(6) gas or silicone oil tamponade. RESULTS: The blood flow
      volume (VOL), blood flow velocity (FLW) and the erythrocyte flow velocity (VEL)
      of fundus in the postoperative RD eyes were reduced in the comparison with those
      of the fellow control eyes. The VEL of temporal and nasal papillary disk rim had
      significant differences (P < 0.05). The VOL, FLW and VEL of the papillary vessel,
      VOL and FLW of temporal and nasal papillary disk rim, VOL of temporal and nasal
      juxtapapillary retina in the operative eyes were lower than those of the fellow
      eyes (P < 0.01). In the comparison between the eyes having undertaken VR surgery
      and the eyes undertaken SB surgery, the VOL, FLW and VEL of VR surgery were
      reduced more than those of SB surgery. The VEL of temporal and nasal papillary
      disk rim and nasal juxtapapillary retina and FLW of temporal juxtapapillary
      retina had significant differences (P < 0.05). VOL, FLW and VEL of silicone oil
      tamponade eyes were reduced more than those in the operative eyes without
      silicone oil tamponade. VOL of nasal papillary disk rim and juxtapapillary retina
      had significant differences (P < 0.05). VOL and VEL of temporal papillary disk
      rim, VOL of temporal juxtapapillary retina had very significant differences (P <
      0.01). CONCLUSIONS: VR surgery and SB surgery of RD influence papillary and
      retinal VOL, FLW, VEL. The influence of VR surgery on the fundus blood flow is
      more significant than that of SB surgery. The silicone oil tamponade also
      influences the VOL and VEL of the fundus.

PMID- 11955317
TI  - [The effect of platelet-derived growth factor on the formation of proliferative
      vitreoretinopathy].
AB  - OBJECTIVE: To study the actions of platelet-derived growth factor (PDGF) in
      proliferative membrane formation of proliferative vitreoretinopathy (PVR) and
      whether there is the existence of PDGF secreting cells and target cells. METHODS:
      Seven epiretinal membranes (ERM) and 7 subretinal membranes (SRM) obtained from
      eyes undergoing pars plana vitrectomy for retinal detachment complicated by PVR
      were studied. A panel of polyclonal antibodies against PDGF-A and -B ligands,
      PDGF-alpha and -beta receptors, cytokeratin [the marker of retinal pigment
      epithelial (RPE) cell] and glial fibrillary acidic protein (the marker of glial
      cell) was used in immune electron microscopy to examine the expression of PDGF
      and PDGF receptors (PDGFR) in the membranes. The relationship of PDGF protein and
      the main cellular composition of ERM and SRM, retinal pigment epithelial and
      glial cells, was detected by using the double-labeling techniques of immune
      electron microscopy. RESULTS: Positive protein expression of PDGF-A located in
      the cytoplasm of some cells was detected in 7 ERMs and 5 of 7 SRMs. Positive
      protein expression of PDGF-B was detected in 7 ERMs and 5 of 6 SRMs, and it was
      located in the cytoplasm of some cells, especially in the secreting granules. RPE
      cells and glial cells were identified in ERMs and SRMs. PDGF receptors were not
      detected in the ERM and SRM in this research. Double-labeling of PDGF and
      cytokeratin showed that RPE cells were the secreting cells of PDGF. Similarly,
      double-labeling of PDGF and glial fibrillary acidic protein showed that glial
      cells were the secreting cells of PDGF. CONCLUSIONS: PDGF can be secreted by the
      cells of ERM and SRM. PDGF plays an important role in the pathogenesis of PVR.
      RPE and glial cells are the secreting cells of PDGF. The results indicate that
      PDGF affects cellular behavior by autocrine or paracrine mode in the formation of
      PVR.

PMID- 11955318
TI  - [The influencing actions of NMDA, MK801 and Ca(2+) on cultured retinal neuron
      cells].
AB  - OBJECTIVE: To investigate the effects of N-methyl-D-aspartate (NMDA), MK801 (non
      competitive blocking agent of NMDA receptor) and Ca(2+) on cultured retinal
      neurons and the interaction of these reagents. METHODS: NMDA, MK801 and Ca(2+)
      were singly and jointly added to the retinal neurons after primary culture for 7
      days which obtained from 1 - 3 day-old postnatal Sprague-Dawley rat. The cells
      were identified with anti-neurofilament protein (NF), Thy1.1 and anti-glial
      fibrillary acidic protein (GFAP) monoclonal anti-body. The effects were assessed
      quantitatively using the trypan blue exclusion methods. RESULTS: Neuronal death
      which induced by 200 micromol/L NMDA and 10 mmol/L Ca(2+) was significantly
      different from that of the control, 20 micromol/L MK801 had no significant effect
      on cultured retinal neurons, and did not protect the cell from neurotoxicity of
      Ca(2+), but could block the neurotoxicty of NMDA. CONCLUSIONS: NMDA and certain
      concentration of Ca(2+) are neurotoxic to retinal neurons in the primary
      cultured. MK801 can block the neurotoxicity of NMDA, but not the neurotoxicity of
      Ca(2+). Neuronal death induced by Ca(2+) may get through another mechanism.

PMID- 11955319
TI  - [A long-term observation of laser in situ keratomileusis for myopia].
AB  - OBJECTIVE: To evaluate the long-term results of laser in situ keratomileusis
      (LASIK) for the correction of myopia. METHODS: A total of 1 285 eyes with
      preoperative refraction of -1.50 - -25.00 diopters were treated with LASIK. Based
      on the preoperative refraction, the patients were divided into 3 groups (-1.50 - 
      6.00 D, -6.12 - -12.00 D, -12.12 - -25.00 D). The mean follow-up was 26.7 months
      and the results were concluded and analyzed. RESULTS: At two years, respectively
      93.4%, 86.7% and 65.5% in the above three groups were within +/- 1.00 D, 84.4%,
      79.7%, 42.1% were within +/- 0.50 D; the uncorrected visual acuity was >/= 0.5 in
      99.6%, 93.8% and 62.6% of the patients, and 90.4%, 68.6%, and 27.2% had vision of
      >/= 1.0. Thirty-nine eyes with regression or under correction, and 2 eyes with
      epithelial ingrowth had been retreated with LASIK. CONCLUSIONS: LASIK is
      effective and safe for the correction of mild, moderate, high and super-high
      myopia. The results of follow-up for two years are stable.

PMID- 11955320
TI  - [An analysis of adhered cells on the surface of F-heparin surface modified
      intraocular lenses implanted into rhesus monkeys' eyes].
AB  - OBJECTIVE: To study the biocompatibility of F-heparin surface modified
      intraocular lenses (IOLs) by observing cellular reaction on the surface of IOLs
      implanted into the rhesus monkeys' eyes. METHODS: Ten monkeys (20 eyes) were
      classified into two groups. PMMA IOLs and F-heparin modified IOLs were
      respectively implanted into 10 monkeys' eyes. The IOLs were examined with
      computer image analysis, light microscope (LM) and scanning electron microscope
      (SEM) at postoperative 180 and 360 days. RESULTS: A few of adhered cells were on
      the surface of the central part of the IOL and more on the border of the IOL
      optics. The giant cells deposited on the surface occupied the largest area and
      the number of the macrophages was the greatest. The cells deposited on the
      surface of the IOLs in the F-heparin modified group were less than that in the
      non-modified group. In the modified group, there was fine granular proteinaceous
      membrane on the surface of the IOLs, but in the non-modified group there was
      fibrinous reticular proteinaceous membrane. CONCLUSION: The biocompatibility of
      the F-heparin surface modified IOLs is better than that of non-modified PMMA
      IOLs.

PMID- 11955321
TI  - [The role of taurine as hydroxyl radical inhibitor and its effect on lipid
      peroxidation in selenite cataract].
AB  - OBJECTIVE: To study the role of taurine as hydroxyl radical and superoxide anion
      radical inhibitor in vitro and evaluate the effect of intraperitoneal injection
      of taurine on peroxidation in rat selenite cateractous lenses. METHODS: Electron
      spin resonance (ESR) was used to detect hydroxyl radical and superoxide anion
      radical. The concentrations of malondialdehyde (MDA) in normal lenses, selenite
      injected lenses and taurine-treated lenses were measured on the 2 nd, 5 th, 9 th
      and 14 th days after the first injection of selenite. RESULTS: Taurine was an
      inhibitor of hydroxyl radical and superoxide anion radical. Its effect was very
      obvious. The concentration of MDA in selenite-injected lenses increased
      significantly after injection of selenite and became higher with the development
      of cataract. The concentration of MDA in taurine-treated lenses was lower than
      that in selenite-injected lenses. CONCLUSION: Taurine is an inhibitor of hydroxyl
      radical and superoxide radical. It can prevent lipid peroxidation in selenite
      cataractous lenses.

PMID- 11955322
TI  - [Cell cycle block and apoptosis in rabbit lens epithelial cells induced by
      hydroxycamptothecine].
AB  - OBJECTIVE: To study the cell cycle block and apoptosis induced by
      hydroxycamptothecine (HCPT) in cultured rabbit lens epithelial cells (RLECs) and
      its affect on the gene expression of fas/fas-L in RLECs. METHODS: Flow cytometry
      was used to examine HCPT-induced cell cycle block in cultured RLECs. We observed
      cell morphological changes with light microscope and electron microscope.
      Apoptosis was detected by terminal deoxyribose transferase-mediated deoxy-uridine
      triphosphate nick end labeling (TUNEL) assay. The TUNEL assay was performed
      following the manufacturer's instruction of in situ cell death detection.
      Expression of Fas and Fas-L was estimated by immunohistochemical staining.
      RESULTS: The flow cytometric analysis showed that the HCPT induced cell cycle
      block was at S phase. The ratio of nucleus and cytoplasm was increased. The
      electron microscopic examinations demonstrated that the HCPT initiated apoptosis
      with typical morphological features. The apoptosis of RLECs treated with HCPT was
      observed by TUNEL assay, and the number of the cells with apoptosis was increased
      with the increase of the HCPT concentration. The HCPT did not affect the gene
      expression of Fas/FasL. CONCLUSIONS: HCPT not only induces mitotic block but also
      induces apoptosis of RLECs which is not mediated by the Fas/FasL signaling
      pathway.

PMID- 11955323
TI  - [A study of cytokine expression in peripheral blood of patients with Graves'
      ophthalmopathy].
AB  - OBJECTIVE: To investigate the expression of interleukin-2 (IL-2), IL-6, soluble
      interleukin-2 receptors (sIL-2R), sIL-6R and tumor necrosis factors (TNF) in the
      peripheral blood in patients with Graves' ophthalmopathy and determine the
      relationship between the serum cytokine levels and the development of the
      disease. METHODS: The level of serum IL-2, IL-6, sIL-2R, sIL-6R and TNF were
      measured in the following 3 groups: acute phase (35 patients), chronic phase (15
      patients) and control (30 patients). Thirty-two of the acute patients were
      received the same examination after a course of glucocorticoid therapy. RESULTS:
      The level of sIL-2R, IL-6, sIL-2R, sIL-6R and TNF in acute patients are (13.86 +/
      2.06) U/ml, (642.86 +/- 123.90) U/ml, (105.11 +/- 15.77) U/ml, (2 438.06 +/-
      218.88) pg/ml, (49.91 +/- 9.081) U/ml respectively, significantly higher than
      that of the normal persons (P < 0.01). After a course of glucocorticoid
      treatment, sIL-2R, sIL-6R, TNF were decreased to (437.75 +/- 90.54) U/ml, (2
      142.31 +/- 301.08) pg/ml, (37.63 +/- 6.12) U/ml, close to the chronic patients,
      but still higher than normal. After treatment, there was no significant
      difference of IL-6 level among the 3 groups (P > 0.05). There was positive
      correlation among IL-6, sIL-2R and TNF level (P < 0.05). CONCLUSION: A serial
      cytokines participate in the occurrence and development of Graves'
      ophthalmopathy. Most of them are related to the course and therapy of the
      disease.

PMID- 11955324
TI  - [Urea soluble fraction of bovine melanin associated antigen and experimental
      study on its uveitogenic activity].
AB  - OBJECTIVE: The purpose of this study was to investigate the uveitogenic activity
      of autoantigen in the bovine iris-ciliary body. METHODS: Urea soluble fraction of
      boveine melanin associated antigen (USF-BMAA) was isolated from the bovine iris
      ciliary body biochemically and determined by SDS-PAGE as well as amino acid
      analysis. Lewis rats and F344 rats were immunized with USF-BMAA emulsified with
      equal volume complete Freud's adjuvant and Bordetella pertussis. RESULTS: A
      strongly stained protein band was observed in the USF-BMAA by SDS-PAGE whose
      molecular weight is approximate 64 000. Amino acid analysis of USF-BMAA showed
      that it contains 17 kinds of amino acids with high content of Glu, Leu and Asp.
      The experimental melanin associated antigen-induced uveitis (EMIU) was
      successfully incited in both eyes of the Lewis and F344 rats. The inflammation
      was mainly located in the anterior uvea, and spontaneously recovered. Mild focal
      choroiditis was present in the rats with severe lesion. However, the inflammation
      was not observed in the retina and pineal gland. CONCLUSIONS: USF-BMAA may be the
      major part of autoantigen of the uveal tract with uveitogenic activity. Unlike
      experimental autoimmune uveoretinitis (EAU) which is incited by the retinal
      soluble antigen (S-Ag) in the rats, no involvement of the retina and pineal gland
      is found in EMIU.

PMID- 11955325
TI  - [A study of experimental carbomer glaucoma and other experimental glaucoma in
      rabbits].
AB  - OBJECTIVE: To establish models of experimental glaucoma in rabbits to investigate
      the treatment of glaucoma. METHODS: Twenty-one normal albino rabbits weighing 2.5
      - 3.0 kg were studied. The rabbits were divided randomly into 4 groups: I, II,
      III and IV. Anterior chamber injection of 0.1 ml of 0.3% carbomer (I), 0.2 ml of
      methylcellulose (II), 0.2 ml of compound methylcellulose (III) and
      subconjunctival injection of 5 mg of dexamethasone (IV) were performed
      respectively on them to induce glaucoma. The intraocular pressure (IOP) was
      monitored with a Tono-pen XL tonometer several times prior to injection and 2
      times per week after injection. The basic IOP in every group served as control.
      RESULTS: Experimental glaucoma occurred in eleven of twelve eyes in group I and
      IOP lasted from 20 to 50 days. The mean IOP levels were 29 - 35 mmHg (1 mm Hg =
      0.133 kPa) and the peak IOP levels were 37 - 45 mm Hg. The IOP in 2 out of 10
      eyes in group II increased to 22 - 50 mm Hg and lasted for 3 days. The IOP of 1
      out of 10 eyes in group III increased to 25 - 40 mm Hg and lasted for 4 days. The
      IOP in eyes of group IV increased only 3 mmHg in the mean and lasted for one
      week. According to the standard, IOP above 22 mmHg for one week as the successful
      experimental glaucoma, group II and III were not the ideal ones and group IV was
      a failure. CONCLUSION: Experimental glaucoma model induced by carbomer has the
      advantages of producing moderate and sustained IOP elevation. The model is easy
      to be carried out. It is simple, reliable, and useful for investigating optic
      nerve and retinal damage in glaucoma and testing the toxicity and efficacy of
      various therapies.

PMID- 11955326
TI  - [A study of the expression of PCNA and the proliferation of bovine lens
      epithelial cell induced by bFGF].
AB  - OBJECTIVE: To observe the effect of the expression of proliferating cell nuclear
      antigen (PCNA) induced by basic fibroblast growth factor (bFGF) on the
      proliferation of bovine lens epithelial cells (BLECs). METHODS: The second
      passage BLECs were cultured with different concentrations of bFGF (0.01 - 100.00
      microgram/L) for 24 - 96 hours, the DNA synthesis of BLEC was measured by (3)H
      TdR incorporation, and the expression of PCNA and the cell cycle were counted by
      the flow cytometer. RESULTS: bFGF promoted the proliferation of BLEC with
      concentration and time dependent manner. The (3)H-TdR incorporation of BLEC was
      increased to 11 772.5 and 10 988.2 respectively much higher than the control
      group (6 550.5). The addition of bFGF 10.00 microgram/L for 24 - 48 hours up
      regulated the expression of PCNA (77.40%), and caused the BLEC population to
      increase in S phase (23.41%) and G(2)/M phase (20.76%). Comparing with the
      control group, there was significant difference (P < 0.05). CONCLUSION: bFGF
      stimulateds the proliferation of BLEC by up-regulating the expression of PCNA and
      changing the cell cycle.

PMID- 11955327
TI  - [Pathological and immunohistochemical study of pineal parenchymal tumors].
AB  - OBJECTIVE: To investigate the histological typing and differentiation as well as
      clinical manifestation and prognosis in pineal parenchymal tumors (PPTs).
      METHODS: The histological typing of 21 PPTs were made by using HE staining.
      Synaptophysin (Syn), neuron special enolase (NSE), neurofilament (NF),
      neuroblastoma (NB), glial fibrillary acid protein (GFAP), cytokeratin (CK),
      desmin (Des) were detected in 20 cases with SP immunohistochemical staining
      methods. Analysis of the clinical data and follow-up were performed. RESULTS: 9
      pineocytomas, 4 pineoblastomas, 8 pineal parenchymal tumors of intermediate
      differentiation were found in 21 PPTs. Immunoreactivity to Syn, NSE, NF, GFAP, NB
      were in 20, 20, 14, 15, 2, while Des and CK were negative in all cases.
      CONCLUSIONS: Pineal parenchymal tumors of intermediate differentiation were
      characterized by a distinctly biphasic pattern, including areas of pineocytoma
      and pineoblastoma, or with intermediate differentiation and transitional feature.
      PPTs expressed neuronic differentiation. Death rate of PPTs were higher inside 1
      year after the operation.

PMID- 11955328
TI  - [A clinicopathological and prognostic study of 22 cases central neurocytoma].
AB  - OBJECTIVE: To investigate the clinicopathological features and prognosis of 22
      cases of central neurocytoma (CNC), representing 0.48% of a series of 4 528
      patients undergoing biopsy for central nervous system tumors. METHODS: The
      histopathological, ultrastructral, immunohistochemical and clinical features of
      CNC were studied by electron microscopic examination and immunohistochemical
      stain for Synaptophysin (Syn), neuron special enolase (NSE), Leu-7, glial
      fibrillary acid protein (GFAP), MBP and proliferating cell nuclear antigen
      (PCNA). RESULTS: The age of the cases ranged from 4 to 44 (average 27.9 years)
      with all tumors localized in the ventricles. In the 18 patients followed up, 14
      were alive for 8 months to 14 years and 11 months after the operation, and 4
      died. The average survival period was 70.7 months. Histologically, the tumor in
      all 22 cases had the oligodendroglioma-like pattern with honeycomb appearance and
      cell-free islands of eosinophilic matrix. Cellular anaplasia, mitosis and
      necrotic areas were rarely seen in the tumors. Immunohistochemical study
      demonstrated strong positivity for Syn, NSE and Leu-7, and negative for GFAP and
      MBP. Ultrastructural features showed presence of round tumor cells with abundant
      cell processes containing microtubules, neurosecretory granules, clear vesicles
      and lysosome-like structures. CONCLUSIONS: The differential diagnosis between CNC
      and oligodendroglioma could not be established by routine light microscopy. The
      importance of immunohistochemical and electron microscopic studies for making a
      correct diagnosis is emphasized. The prognosis of patients is usually favorable,
      even if the tumor was resected subtotally. The relationship between the presence
      of anaplastic histological features in CNC and patient outcome remains unclear.

PMID- 11955329
TI  - [A clinicopathological study of demyelination pseudotumors of the brain].
AB  - OBJECTIVE: To study the clinicopathological characteristics diagnosis,
      differential diagnosis and etiology of demyelination pseudotumors of the brain.
      METHODS: The clinical features, CT, MRI scan findings, corticosteroid therapeutic
      effects and follow-up data of 3 cases of demyelination pseudotumors of the brain
      were analysed, and pathological changes were observed by histologic (HE, Luxol
      fast blue and Bodian) and immunohistochemical (S-P method) techniques. RESULTS:
      The acute onset of demyelination pseudotumors appeared to be more predominant in
      our data. Clinical manifestations included headache, vomiting, a depressed
      conscious level, dysphasia, and paresis. CT, MRI scans showed solitary or
      multiple lesions in cerebral hemisphere. All the patients presented excellent
      response to steroid treatment. Follow-up for a period of 6 to 31 months, revealed
      the absence of progression or recurrence. The pathological changes were mainly
      located in both cerebral hemispheres, in which there were relative axonal
      preservation in foci loss of myelin, reactive gliosis, profuse perivascular
      lymphocytic infiltration and mixtures of foamy macrophages. CONCLUSION:
      Demyelination pseudotumor is a distinct clinicopathologic encephalitic entity.
      The findings of this study suggest that the cause of tumefactive demyelination
      may be related to an allergic reaction triggered by viral infection.

PMID- 11955331
TI  - [Study on diagnostic standards for fine needle aspiration cytological diagnosis
      of breast masses: a comparative analysis of cytology and histology of 951 cases].
AB  - OBJECTIVE: To study the basic morphological factors and the reliability and
      limitations of the diagnostic standards of fine needle aspiration cytology (FNAC)
      of breast masses which drafted. METHODS: A total of 4 309 fine needle aspiration
      biopsy cases of breast were performed and 951 cases of which were checked with
      their histological diagnosis. RESULTS: Of the 413 aspiration smear studies,
      relatively identical morphological features were found on the smears of lesions
      of the same nature. The sensitivity of diagnosis of malignant tumor in 732 cases,
      the specificity of diagnosis of benign lesion in 219 cases and the overall
      accuracy of diagnosis were 97.3%, 97.7%, and 97.4% respectively. The false
      negative rate, potential false positive rate and the overall misdiagnosis rate
      were 2.7%, 2.3% and 2.6% respectively, no false positive diagnosis case was
      found. CONCLUSIONS: (1) The differentiation and the arrangement pattern of the
      tubular epithelial cells and the amount of benign naked nuclear cells are the
      three essential factors in the analysis of morphological changes of FNAC of
      breast mass. (2) The examination of our diagnostic standards of FNAC of breast
      masses shows that the standards are very reliable but have certain limitations
      which need to be resolved by histopathological diagnosis.

PMID- 11955330
TI  - [A clinicopathologic and immunohistochemical study on 76 cases of
      gastrointestinal stromal tumors].
AB  - OBJECTIVE: To study the morphologic and immunohistochemical features of
      gastrointestinal stromal tumors (GISTs) and to explore the reference parameters
      for malignancy. METHODS: Seventy six (76) cases of primary GISTs were
      distinguished from a group of gastrointestinal mesenchymal tumors by use of a
      panel of antibodies such as CD117, CD34 by immunohistochemical EnVision method,
      their biologic behaviors were analyzed by including their follow-up data.
      RESULTS: All patients were adults, age range 32 to 81 years (mean 54 year), male
      39 cases and female 37 cases; the tumors were situated in stomach (36 cases), in
      small intestine (23 cases), colon (2 cases) and rectum (15 cases). The most
      common symptoms were abdomen mass, vague pain and GI bleeding. Forty eight (48)
      cases were mainly located within the muscularis propria, 25 cases outside the
      serosa, and 3 cases below the mucosa. Grossly, they were of soft consistency
      often with hemorrhage, cystification or necrosis. Microscopically, the tumors
      were composed of spindle cells (46 cases) or epithelioid cells (9 cases) and of
      both cells (21 cases), arranged in interlacing fasicles, diffusing sheets,
      pallisading, whirling, alveolar and giant pseudo-rosette shapes. Tumor cells
      often had abundant cytoplasm with light to moderate eosinophilic or slight
      basophilic in staining, the nuclei generally showed spindle, blunted ends, round
      or signet in shape with nucleoli. Immunohistochemically, CD117 and CD34 showed
      diffuse strong expression, the positive rates were 98.7% and 68.4% respectively,
      alpha-SMA, MSA, S-100, PGP9.5 showed focal expression, the positive rates were
      25.0%, 19.7%, 23.7% and 17.1% respectively, vimentin were all positive and
      desmin, GFAP, NF were all negative. Nine cases were benign, 19 cases borderline
      and 48 cases malignant. Follow-up of 20 cases with benign and borderline tumors
      found patients alive without tumor. In the malignant group of 34 cases, 10 cases
      were alive without tumor, 10 cases developed recurrence or metastasis, and 14
      cases died of tumor. Coagulative necrosis, mitotic activity over 10/50HPF, high
      cellularity and obvious pleomorphism were all in the malignant group. In this
      group, tumor necrosis, adhesion in operation, tumor, over 5 cm in diameter,
      mitotic activity over 5/50HPF had significant differences among three groups and
      the 3 years survival rate had a significant difference in tumors with or without
      coagulative necrosis and also in tumors with or without mitotic activity over
      5/50HPF. CONCLUSIONS: GISTs predominantly occurred in middle aged or old
      patients, the tumors had varied cell types and different arrangements, the
      immunohistochemical characters were positive for CD117 and CD34, negative for
      desmin, occasional positive for alpha-SMA, MSA, S-100 and PGP9.5, which were
      helpful to differentiate GIST from leiomyomas and Schwannomas. Coagulative
      necrosis, mitotic activity over 10/50HPF, high cellularity with obvious
      pleomorphism were also helpful parameters for diagnosis of malignancy aside from
      metastasis and invasion. Adhesion, over 5 cm in diameter and mitotic activity
      over 5/50HPF but less than 10/50HPF might be the potential malignant parameters.

PMID- 11955332
TI  - [Expression of telomerase genes in mamary atypical ductal hyperplasia].
AB  - OBJECTIVE: To investigate the relationship of telomerase genes and the malignant
      transformation of atypical mammary ductal hyperplasia. METHODS: Telomerase genes
      hTR and hTRT in 50 cases of mammary hyperplasia (the cases included 6 benign
      hyperplasia, 9 mild atypical hyperplasia, 12 medium atypical hyperplasia, 23
      severe atypical hyperplasia) and 26 cases of breast carcinoma were detected by in
      situ hybridization. RESULTS: The expression of hTR and hTRT mRNA were weak or
      negative in benign hyperplasia (1/6, 0), weaker in mild-moderate atypical
      hyperplasia (2/9, 1/9, 4/12, and 3/12), strong in severe atypical hyperplasia
      (14/23, 60.9% and 12/23, 52.1%), while very strong expression (23/26, 88.5% and
      21/25, 80.8%) in carcinoma of the breast. The difference between mild-moderate
      atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia
      was significant (P < 0.05) and the difference between severe atypital hyperplasia
      and intraductal carcinoma was not significant (P > 0.05). CONCLUSIONS: Telmerase
      genes (hTR, hTRT) expression is closely related to the malignant transformation
      of atypical hyperplasia. The reactivated telomerase may play a crucial role in
      the development of breast cancer.

PMID- 11955334
TI  - [Giant cell fibroblastoma: a clinicopathologic analysis of seven cases].
AB  - OBJECTIVE: To study the clinical, pathological and immunohistochemical features
      of giant cell fibroblastoma (GCF), with emphasis on its differential diagnosis
      and histogenesis. METHODS: Seven cases of GCF were investigated by light
      microscopy and immunohistochemistry. RESULTS: Six cases occurred in children, and
      one occurred in a 35 year-old adult (mean 9.4 years). Five were male and two were
      female. Clinically, all cases appeared as slowly growing painless nodules located
      in the dermis or subcutis of the trunk and extremities. Microscopically, the
      poorly circumscribed tumor was composed of a proliferation of slightly to
      moderately atypical spindle cells which were arranged in parallel or wavy
      fascicles, and embedded in a fibromyxoid to collagenous background. The
      pathognomonic feature consisted of irregular distributed cleft-like or sinusoid
      like pseudovascular spaces lined with a discontinuous layer of pleomorphic
      spindle cells and multinucleate giant cells. There was transition in shape
      between these two cells. Immunohistochemially, both cells expressed vimentin and
      CD34. Follow-up information in five cases showed local recurrences in two cases.
      CONCLUSIONS: (1) GCF is a distinctive fibroblastic tumor of intermediate
      malignancy that occurs predominantly in children. Recognizing its clinical and
      pathological characteristics is important to avoid misdiagnosis with other
      lesions with similar features. (2) GCF shared clinical, immunohistochemical and
      cytogenetic features with its adult counterpart-dermatofibrosarcoma protuberans
      (DFSP). The additional coexistence of GCF and DFSP areas in some primary cases
      and the reciprocal transformation in recurrent tumors all suggest that they are
      two closely related entities, possibly representing two members of the CD34
      positive dendritic neoplasms.

PMID- 11955333
TI  - [Clinicopathological observaton on nodular regenerative hyperplasia of the
      liver].
AB  - OBJECTIVE: To discuss the clinicopathological characteristics and differential
      diagnosis of nodular regenerative hyperplasia of the liver (NRH). METHODS: 9
      cases of NRH were collected and their clinical and pathological features were
      reviewed. RESULTS: NRH is an important cause of non-cirrhotic portal hypertension
      which is frequently associated with autoimmune disease, malignant tumors and
      administration of certain drugs. Clinically NRH presents portal hypertension, but
      with almost normal liver function. Pathological examinations found diffuse
      nodules of hyperplastic hepatocytes in liver without fibrous septa in between.
      The obliteration of portal veins are frequently seen. This suggests that ischemia
      caused by alteration of portal veins may play an important role in the
      development of nodular regenerative hyperplasia of the liver. CONCLUSION:
      Histopathology of NRH is characteristic and it should be differentiated from
      cirrhosis, focal nodular hyperplasia and hepatocellular adenoma.

PMID- 11955335
TI  - [The expression of thyroid transcription factor-1 in pulmonary sclerosing
      hemangioma and a further investigation on histogenesis of the tumor].
AB  - OBJECTIVE: To investigate the histogenesis and pathologic features of pulmonary
      sclerosing hemangioma (SH) and its expression of thyroid transcription factor-1
      (TTF-1). METHODS: Seventeen cases of pulmonary sclerosing hemangioma were
      reevaluated and 12 cases were immunostained with a panel of antibodies including
      TTF-1, EMA, cytokeratin, etc. Six cases were studied by electron microscopy.
      RESULTS: All cases exhibited the classic histologic features with variable
      proportions of solid, papillary, hemorrhagic or hemangiomatic, and sclerotic
      pattern. The tumours consisted of solid sheets or aggregates of pale polygonal
      cells and papillae and clefts lined by cuboidal or columnar cells. Both TTF-1 and
      EMA expressions were observed in the surface lining cuboidal cells and the pale
      polygonal cells. In only one case both chromogranin and synaptophysin showed
      weakly positive in few polygonal cells and a small number of granules with high
      electron density was found in the polygonal cells by electronic microscopy.
      CONCLUSIONS: It is suggested that pulmonary sclerosing hemangioma is an
      epithelial neoplasm derived from primitive respiratory epithelium capable of
      differentiating toward pneumocytes or Clara cells. The immunohistochemical
      markers such as TTF-1, EMA and CK play an important part in diagnosis of SH.

PMID- 11955336
TI  - [The effects of wild-type PTEN transfection on gene expressions of
      glioblastomas].
AB  - OBJECTIVE: To study the effects of wild-type PTEN on gene expressions of
      glioblastomas. METHODS: Glioblastoma U87MG cells, which express inactivated PTEN,
      were transfected with wild-type PTEN constructs and stable transfected clones
      were selected. Then, cDNA microarray analyses were used to identify
      differentially expressed genes in wild-type PTEN transfected cells and control
      cells. RESULTS: Transfected wild-type PTEN inhibited the proliferation of U87MG.
      By cDNA microarray analyses, 89 cDNA clones were identified, which were
      differentially expressed in wild-type PTEN transfected cells and control cells.
      Among these genes, 13 genes were unknown and 76 genes were known genes, including
      glial fibrillary acidic protein, p21/WAF1, human TGF-beta inducible early
      protein, human DNA fragmentation factor 45 etc. CONCLUSION: Wild-type PTEN can
      affect the expressions of multiple genes, by which it regulates the
      proliferation, differentiation and apoptosis of glioblastomas.

PMID- 11955337
TI  - [Monoclonal antibodies against human telomerase reverse transcriptase:
      preparation, characterization, and application].
AB  - OBJECTIVE: To develop monoclonal antibodies against the catalytic subunit of
      human telomerase hTERT for its expression detection of human tumors. METHODS: A
      dominant epitope in hTERT (peptide hTERT(9))was automatically synthesized based
      on Fmoc method, and was used to immunize BALB/c mice. Hybridomas were generated
      and screened by ELISA for specific monoclonal antibodies, and the
      characterization of which were performed by Western blotting and
      immunohistochemical staining. RESULTS: Antigenic peptide hTERT(9) was synthesized
      and confirmed by MALDI-TOF-MS and HPLC analysis. Three hybridoma cell lines
      secreting anti-hTERT(9) antibodies designated as H4, G8 and A11 were established
      after primary screening and consequent three rounds of limited dilution. Both of
      H4 and G8 were IgM, while A11 was IgG1 in isotyping. The competitive assay showed
      that the antibodies were hTERT(9) specific, and the affinity of G8 was stronger
      than that of H4 and A11 assayed by affinity ranking. However, in Western
      blotting, both of H4 and G8 stained an about 123 000 protein band with HeLa and
      293 cell extracts but not with normal 2BS cells. Besides, positive staining
      presented in the nucleus of HeLa, while 2BS was non-reactive
      immunohistochemically. The sections from paraffin-embedded blocks of 127 cases of
      human cancer, 40 of precancerous and 19 of benign tumors were in situ stained by
      G8 antibody, the results showed that the human cancer tissues were 80.31%
      (102/127) positive in specific nuclear reaction, on the contrary, only a minority
      of precancerous lesions present weak positive (17.5%, 7/40), and negative in
      benign tumors (0/19). CONCLUSIONS: The monoclonal antibodies developed against
      synthetic peptide were hTERT-specific and could recognize both the native and the
      denatured form. Thus their use in immunoblotting or immunohistochemistry for
      detecting the telomerase hTERT expression of cancer cell and tissues was
      promising.

PMID- 11955338
TI  - [A study on DNA damage of mouse livers induced by methylmercury].
AB  - OBJECTIVE: To study the DNA damage induced by methylmercury (MeHg) in mouse
      hepatocytes. METHODS: The single cell gel electrophoresis (SCGE) was used to
      study the DNA damage of mouse hepatocytes when treated with different doses in
      vivo and in vitro. RESULTS: After treated with high, middle and low doses of MeHg
      for 12 h in vivo (i.p.), the proportion of DNA damage was increased and the ratio
      of living cells was decreased; and both effects showed significantly dose-effect
      relationships. Similar effects were found when different MeHg doses were
      administered to hepatocytes in vitro for 1 h. CONCLUSION: MeHg induces DNA damage
      in mouse hepatocytes.

PMID- 11955339
TI  - [Effects of health promotion for eight years on knowledge, attitude and behavior
      of cardiovascular diseases in rural Fangshan District, Beijing].
AB  - OBJECTIVE: To evaluate the effects of health promotion for eight years on
      cardiovascular diseases based on the changes in knowledge (K), attitude (A) and
      behavior (B) (KAB) before and after intervention in rural population of Fangshan,
      Beijing. METHODS: Five townships in Fangshan District, Beijing were divided into
      intervention and control communities with cluster sampling. Totally 772 farmers
      were selected randomly for interviews with a questionnaire of KAB, including 424
      in the intervention communities (IC) and 348 in the control communities (CC) in
      1992. After community-based health promotion and education on cardiovascular
      prevention for eight years, 895 farmers, including 431 in IC and 464 in CC, were
      selected randomly again in 1999 to be interviewed with the same questionnaire of
      KAB used in 1992. RESULTS: From 1992 to 1999, knowledge of cardiovascular
      diseases was significantly improved in residents of IC (P < 0.01) and CC.
      Compared to the residents in CC, there was a net increase in knowledge in
      residents of IC. Significant improvement was found in 10 and 11 of the 18 items
      of knowledge in males and females (P < 0.01), respectively. Level of knowledge in
      cardiovascular diseases was significantly higher in the residents of IC than
      those of CC in 1999. Proportions of those with positive attitudes and appropriate
      behaviors were significantly elevated in the residents of IC (P < 0.01), as well
      as prevalence of smoking and alcohol drinking decreased. However, as compared to
      CC, attitude and behavior in most aspects in the residents of IC changed
      positively, but in few aspects changed negatively. It suggested knowledge
      improved better than attitude and behavior changed. CONCLUSIONS: Community-based
      health promotion and education for a longer term had obvious effects on
      improvement of knowledge in cardiovascular disease for rural population, but
      slower effects on changes in attitude and behavior, which suggested there still
      existed certain barriers to transform knowledge into healthy behavior.

PMID- 11955340
TI  - [Application of SCGE-FPG in the study of arsenic-induced oxidative DNA damage in
      PHA-stimulated and unstimulated human lymphocytes].
AB  - OBJECTIVE: To confirm that arsenic (As) induces oxidative DNA damage in
      phytohemagglutinin (PHA)-stimulated and unstimulated human lymphocytes. METHODS:
      The alkaline comet assay combined with specific enzyme (Formamidopyrimidine-DNA
      glycosylase, FPG) digestion was used to measure As-induced base damage. RESULTS:
      The enzyme-sensitive sites were readily detected with the alkaline comet assay
      after the cells were treated with 10 micromol As for 2 hours. The repair patterns
      observed for FPG-created DNA single strand breaks (SSBs) in As-treated cells were
      comparable to those in hydrogen peroxide (H(2)O(2))-treated cells. The enzyme
      created SSBs, As-induced base damage, were more significantly revealed in PHA
      stimulated lymphocytes. About 63% and 68% of SSBs induced by As and H(2)O(2),
      respectively, were repaired in PHA-stimulated lymphocytes by 2-hour repair
      incubation, but about 34% and 43%, respectively, were repaired in unstimulated
      cells. About 40% and 49% of base damage induced by As and H(2)O(2), respectively,
      were repaired in PHA-stimulated lymphocytes, but about 19% and 21 %,
      respectively, were repaired in unstimulated cells. CONCLUSIONS: As induces
      oxidative DNA damage in human lymphocytes within micromolar concentrations. Like
      the damage induced by H(2)O(2), As-induced DNA damage was more slowly repaired in
      unstimulated lymphocytes.

PMID- 11955342
TI  - [A 1:2 matched case-control study on congenital external malformation during
      perinatal period].
AB  - OBJECTIVE: To investigate the risk factors for congenital external malformation.
      METHODS: A 1:2 matched case-control study was conducted with 52 cases of
      congenital external malformation during perinantal period collected from
      surveillance in Baoan District of Shenzhen City from January to June in 2000.
      RESULTS: Simple and multiple conditional logistic regression analysis showed that
      the major risk factors for congenital external malformations during perinatal
      period were preterm labor (beta(k) = 1.4171, s(theta, beta(kappa)) = 0.4601, OR =
      4.115), adverse mental stimulus (beta(kappa) = 2.1870, s(theta beta(kappa)) =
      0.7873, OR = 8.909), taking medicine (beta(k) = 1.9178, s(theta beta(kappa)) =
      0.8072, OR = 6.808) and exposure to hazardous chemicals during early pregnancy
      (beta(k) = 0.9602, s(theta beta(kappa)) = 0.4262, OR = 2.612). CONCLUSIONS:
      Congenital external malformation during perinatal period was caused by multiple
      risk factors and results of the study showed that environmental and mental
      factors were in obvious connection with its occurrence.

PMID- 11955341
TI  - [Neonatal screening for congenital adrenal hyperplasia in Shanghai areas].
AB  - OBJECTIVE: To investigate the incidence of congenital adrenal hyperplasia (CAH)
      in Shanghai areas by a neonatal screening program. METHODS: Heel prick blood
      samples were collected from 50 600 newborns in 50 maternal and child health care
      hospitals and maternity hospitals 72 hours after their birth and adsorbed onto
      standard filter paper for determining 17-hydroxyprogesterone (17-OHP) by enzyme
      linked-immunosorbent assay (ELISA). RESULTS: Level of 17-OHP was significantly
      increased in eight cases of the 50 600 newborns, three cases of whom with
      established CAH with hyponatremia, hyperkalemia and hypertestosteronemia duo to
      21-hydroxylase deficiency, and other five cases with high level 17-OHP due to
      preterm delivery. CONCLUSIONS: Determining 17-OHP level on dried blood spotted
      filter paper is a reliable and practical approach for CAH mass screening in
      neonates. The incidence of CAH in Shanghai areas was 5.93 per 100 000 newborns
      (3/50 600).

PMID- 11955343
TI  - [The cytotoxicity of maitotoxin to LLC-PK(1) and its antagonism to calcium
      channel blocking agents].
AB  - OBJECTIVE: To study the cytotoxicity of maitotoxin (MTX) and its protective
      effects on calcium-channel blocking agents, so as to provide the data for control
      and treatment of MTX poisoning. METHODS: Cytotoxicity was measured by MTT
      detecting system, and cytoplasmic free [Ca(2+)]i was measured by F-4500
      fluorometry. RESULTS: Incubation with 8 ng/ml MTX for 3 h reduced the survival
      ratio of LLC-PK(1) cells. The response was found in a time- and concentration
      dependent manner, with significant differences as compared with the control
      group. The MTX-induced increase in [Ca(2+)]i was inhibited by Verapamil and
      Nifedipine at 5 x 10(-5) mol/L and 1 x 10(-4) mol/L respectively. Both of them
      significantly reduced the death of the LLC-PK(1) cells. CONCLUSIONS: Cytotoxicity
      of MTX may be caused by the elevated intracellular [Ca(2+)]i. Calcium-channel
      blocking agents could protect LLC-PK(1) cells from injury by MTX.

PMID- 11955344
TI  - [The effect of vitamin C in oxidative modification of low-density lipoprotein
      induced by macrophage and copperion].
AB  - OBJECTIVE: To study the effect of vitamin C on preventing oxidative modification
      of low density lipoprotein cholesterol (LDL) in vitro. METHODS: Different levels
      of vitamin C were added to two different systems of lipid peroxidation of LDL
      induced by either Cu(2+) or macrophage. The level of VC in systems induced by
      Cu(2+) were 10, 50, 100 and 200 micromol/L respectively and by macrophage were
      50, 100, 200 micromol/L respectively. Vitamin E (200 micromol/L) and VC(0) (0
      micromol/L) were served as positive and negative control respectively. The
      content of TBARS, Ox-LDL, fluorescent compounds, electrophoretic mobility of LDL
      and the lag-phage of oxidation of LDL were measured. RESULTS: In the oxidative
      systems induced by Cu(2+), the groups with higher levels of VC (100, 200
      micromol/L) reduced the levels of TBARS, Ox-LDL at 3, 6, and 9 hour after adding
      Cu(2+), but low dose groups (10, 50 micromol/L) had no the effects. In the
      macrophage systems, higher levels of VC (100, 200 micromol/L) significantly
      reduced levels of fluorescent compounds and TBARS, and also lowered
      electrophoretic mobility of LDL and increased the lag-phage of oxidation of LDL.
      CONCLUSION: Vitamin C has dual effect on oxidation of LDL. Low dose treatment
      enhanced oxidation of LDL, but high doses has anti-oxidative effects on LDL.

PMID- 11955345
TI  - [Effect of lead acetate on the apoptosis and the expression of bcl-2 and bax
      genes in rat brain cells].
AB  - OBJECTIVES: To explore the effect of lead acetate on the apoptosis of rat brain
      neural cells and the relationship between the apoptosis and the bcl-2 as well as
      bax gene expression. METHODS: Lead acetate was given to SD rats by
      intraperitoneal injection for 5 days at the dosage of 25, 50 and l00 mg/kg body
      weight respectively. The rates of apoptosis and the expression of bcl-2 (Bcl-2)
      and bax (Bax) in neural cells from cerebral cortex, hippocampus and carebellum
      were measured respectively by flow cytometry (FCM). RESULTS: The rates of
      apoptosis in neural cells from cerebral cortex, hippocampus and cerebellum in
      every treatment group were significantly higher than that of control (P < 0.01),
      and there was a significant dose-response relationship (r = 0.998, 0.989 and
      0.997 respectively). The expression of bcl-2 was significantly decreased, whereas
      bax was significantly increased, in neural cells from cerebral cortex,
      hippocampus and cerebellum in every lead acetate treatment group (FI) compared
      with the control group, and there was a significant dose-response relationship (r
      = -0.886, -0.787 and -0.832 respectively for bcl-2, r = 0.971, 0.988 and 0.991
      respectively for bax). The value of Bcl-2/Bax in every treatment group decreased
      significantly compared with control, and there was a nice dose-response
      relationship (r = -0.863, -0.829 and -0.999, respectively). Correlation analysis
      showed that rates of apoptosis were inversely correlated with the expression of
      bcl-2 (r = -0.750, -0.509, and -0.667, respectively), whereas positively
      correlated with the expression of bax (r = 0.748, 0.56l, and 0.668,
      respectively). And there were inverse correlations between the rates of apoptosis
      and Bcl-2/Bax expression. CONCLUSION: Lead may induce apoptosis in rat brain
      neural cells through the down regulation of bcl-2 and the up regulation of bax
      gene expression.

PMID- 11955346
TI  - [Correlationship between body mass index and mortality in the middle-aged and
      elderly population of Beijing City].
AB  - OBJECTIVE: To explore the association between body mass index (BMI) and mortality
      in the middle-aged and elderly population of Beijing. METHODS: A prospective
      cohort study was carried out in a natural population (aged 40 and over) in
      September 1991, totaling 6 209 subjects. After a baseline survey for risk
      factors, all the subjects were followed-up throughout December 1999. All deaths
      occurred during the follow-up period were registered and encoded according to ICD
      9. Proportional hazard regression was used to examine the relationship between
      BMI (body weight in kilograms/height in square meters) and overall and cause
      specific mortality. RESULTS: During the past ten years, five leading causes of
      death in the middle-aged and elderly population of Beijing were cardiovascular
      disease (CVD), cor pulmonale, digestive malignant tumor, sudden death without
      definite cause and lung cancer, which accounting for 33.3%, 13.8%, 11.2%, 7.4%
      and 5.6% of the total deaths, respectively. The minimum overall mortality in all
      population and in non-smokers were seen in those with BMI of 23.6 - 26.2.
      Compared with those with BMI of 23.6 - 26.2, the relative risks (RR) for all
      cause mortality in all population and non-smokers with BMI less than 21.2 and
      equal to or greater than 26.2 were 1.7, 1.3, 1.9 and 1.5, respectively after
      adjusted for age, gender, smoking and alcohol drinking. BMI correlated positively
      with death risk due to CVD in non-smokers, with an RR of 1.2 for those with BMI >
      26.2 to non-smokers with BMI < 21.2 after adjusted for age, gender and alcohol
      drinking. A U-shaped correlationship between BMI and deaths due to other specific
      causes, including cor pulmonale, digestive malignant tumor, lung cancer,
      pneumonia and sudden death without definite causes. With the minimum cause
      specific death rates all at BMI of 23.6 - 26.2. In comparison with those with BMI
      of 23.6 - 26.2, RRs for these five cause-specific mortality were 14.8, 1.1, 5.6,
      2.4 and 2.6, respectively for non-smokers with BMI < 21.2 and 3.0, 1.9, 3.7, 2.2
      and 1.5, respectively for non-smokers with BMI >/= 26.2 after adjusted for age,
      gender, and alcohol drinking. The proportion of deaths due to CVD was the highest
      in each BMI group, with a range of 28.0% - 54.8%. CONCLUSIONS: There exists a U
      shaped correlationship between BMI and overall mortality in the middle-aged and
      elderly population in Beijing. CVD remains the top leading cause of death in
      natural population, and its death risk increased with BMI.

PMID- 11955347
TI  - [The dose-response relationship study between the quantitative morphological
      stereology on thyroid and different iodine doses in mice].
AB  - OBJECTIVE: To study the dose-response relationship between the quantitative
      morphological stereology on thyroid and different iodine doses in mice. METHODS:
      Weaning Kunming mice were randomly divided into seven groups. The mice were fed
      for 100 days with distilled water containing different KIO3 concentrations, i.e.
      50, 250, 500, 1 000, 1 500, 2 000, and 3 000 microgram/L respectively. The 50
      microgram/L (proper iodine concentration) group was control group, and the groups
      of 250 approximately 3 000 microgram/L were high iodine groups. The stereology
      parameters of thyroid follicle and follicular cavities were measured with HPIAS
      1000 (High Resolution Pathological Image & word Analysis System). The stereology
      parameters included mean surface, volume on area, volume on circumference,
      specific surface, numerical density on area, spherical factor, the percentage of
      mean surface and mean volume of the follicular epithelial cell in thyroid
      follicle was further calculated. RESULTS: Positive correlations was observed
      between the thyroid absolute and relative weight, goiter rate and different
      iodine doses. And the thyroid absolute and relative weight of mice in the 250
      microgram/L group was significantly different from that in 50 microgram/L group.
      The goiter rate of mice in different high iodine groups was in conformity with
      that of epidemiological investigation. The goiter rate of mice in 500 microgram/L
      group was different from that in 50 microgram/L group. Positive correlations were
      observed between mean surface, volume on area, volume on circumference, spherical
      factor and iodine doses, but the negative correlations were observed between
      numerical density on area, specific surface, the percentage of mean surface and
      mean volume of the follicular epithelial cell in thyroid follicle and iodine
      doses. CONCLUSIONS: When Iodine doses are between 250 approximately 3 000
      microgram/L, the dose-response relationship was observed between the
      morphological stereology parameters of thyroid follicle and follicular cavities
      and iodine doses, and when the dose of iodine is 250 microgram/L, it is possible
      to induce colloid goiter of mice. The goiter rates of mice resulted by different
      high iodine doses were in conformity with that of the epidemiological
      investigation of people.

PMID- 11955348
TI  - [Analysis of risk factors for cervical cancer in Xiangyuan County, Shanxi
      Province].
AB  - OBJECTIVES: To investigate the risk factors for cervical cancer in the areas of
      high incidence, and provide evidence for current intervention of cervical cancer.
      METHODS: In the areas of Xiangyuan County, Shanxi Provicne with high incidence of
      cervical cancer, 1 997 women were interviewed using a questionnaire, including
      baseline information, menstrual, marital and pregnancy histories, sexual
      behavior, health habits, contraception, medical history and family history of
      cancer, etc., after its screening with six kinds of methods. All subjects,
      including 84 cases with pathological diagnosis of greater than cINI, and 1 784
      cases with pathological diagnosis of normal, were tested for high-risk HPV.
      RESULTS: The overall rates of HPV infection were 20.8% (415/1 997) in high-risk
      subjects, 97.7% and 14.2% in the cases and control groups, respectively.
      Univariate analysis showed that risk factors with statistical significance
      included high-risk HPV infection, age at first sexual intercourse, history of
      pregnancy and abortion, the number of sexual partners and family history of
      cancer. Analysis with non-conditional logistic regression model revealed high
      risk HPV infection, multiple sexual partners and family history of cancer
      associated obviously with occurrence of cervical cancer. In addition, there was
      significantly positive relationship between HPV infection, which increased with
      the number of sexual partners, and extramarital sexual activity both in males or
      females. CONCLUSIONS: The main risk factor for cervical cancer in this region was
      high-risk HPV infection, which related to sexual behavior, hygienic habits during
      menstruation and puerperium. It was particularly important to detect and treat
      precancerous lesions and to implement behavior modification. In addition, further
      research on genetic susceptibility was suggested.

PMID- 11955350
TI  - [Distraction osteogenesis for repair of cleft palate: an experimental study].
AB  - OBJECTIVE: To observe the repair of cleft palate (CP) bone defect under the
      application of distraction osteogenesis (DO); to investigate the correction
      mechanism in thin bone of palatal shelf and to search a possible new treatment
      approach for repair of CP. METHODS: 14 cats were assigned randomly to 3 groups:
      (1) Empty control, 2 cats unoperated with euthanasia at the end of 2 weeks; (2)
      Experimental control, 2 cats underwent 8 mm x 18 mm palatal osteoectomy in
      saggital direction as the experimental model of CP with euthanasia in 6 weeks;
      (3) Experimental group, 10 cats were performed the same palatal osteoectomy as
      group (2), the newly designed and individual manufactured intraoral distractors
      were fixed to teeth by brackets and to bilateral palate bone across the defect
      with titanium miniscrews. 4 weeks later the transport disc (TD) osteotomy were
      performed and gradual distraction was started after 6 days latency period at the
      rate of 0.4 mm x 2/day till the TD reached the opposite edge of the CP.
      Roentgenographic, gross meterage and ultrastructural observation were performed
      2, 4, 6, 8, 12 weeks after completion of distraction. RESULTS: All the
      examinations revealed the TD recombination to the opposite bone edge of the CP,
      simultaneously, the proportional expansion of overlay mucoperiosteal flap was
      achieved. The bone defect were filled with de move osteogenesis.
      Roentgenographically, the new bone mineralization was along the DO vector,
      developed from the bone cut edges bilaterally to the central translucent zone
      until turned to thin fissure. Comparison of the plaster casts showed no change in
      the occlusion or dentomaxillofacial framework. CONCLUSIONS: The intraoral
      distractor is able to get both effective distraction and steady fixation. The
      examination results suggest that the CP bone and soft tissue defect could be
      repaired and acheived functional reconstruction under DO, which could be a new
      treatment approach for repair of CP.

PMID- 11955349
TI  - [DNA vaccine encoding Streptococcus mutans surface protein protected gnotobiotic
      rats from caries].
AB  - OBJECTIVE: Protein of Streptococcus mutans is considered as one of the virulence
      factors due to its ability to mediate the initial attachment of Streptococcus
      mutans to tooth surface. In this study, an anticaries DNA vaccine pCIA-P was used
      to immunize rats. The expression of PAc in different tissues in vivo, specific
      immune response and protection effects against dental caries were observed.
      METHODS: Plasmid pCIA-P was injected into rats by two different routs:
      intramuscular injection (i.m.) and targeted salivary gland immunization (TSG).
      Immunohistochemistry technique was used to detect the expression of PAc.
      Gnotobiotic rats were vaccinated with pCIA-P by three different approaches: TSG,
      intramuscular injection and buccal mucosal injection (i.o.). The specific immune
      responses were evaluated by ELISA and their anticaries effects were evaluated by
      Keyes caries scores. RESULTS: PAc was expressed in the sarcoplasm and sarcolemma
      of muscle fibers and submandibular glands, especially strongly positive in duct
      regions. The levels of serum specific anti-PAc IgG and salivary specific anti-PAc
      IgA in TSG immunization and buccal mucosal immunization group were significantly
      higher than those of other groups. The Keyes caries scores of those two groups
      were significantly lower than those of other groups. CONCLUSION: The plasmid pCIA
      P could provoke specific immune responses as a novel immunogen. Mucosal
      immunization with pCIA-P appears to be an effective genetic immunization method
      against dental caries.

PMID- 11955351
TI  - [Establishment of human immortalized oral epithelial cell line HIO615 induced by
      HPV16 E6 and E7].
AB  - OBJECTIVE: To establish an immortalized oral epithelial cell line. METHODS:
      Normal human oral epithelial cells were transfected with HPV16E6/E7 open reading
      frames using recombinant retroviral system pLXSN. Expression of HPV16E6 and E7
      protein were tested by Western blot in three kinds of cells. To define cellular
      biological characterization of HPV16E6/E7 transfected cells, a series analysis
      were performed, including protraction of growth curve, HE staining,
      immunocytochemical staining and scanning electron microscope observation. The
      tumorigenicity was assessed by colony formation and transplanting the cells into
      nude mice. RESULTS: Human oral epithelial cells transfected with HPVE6/E7 has
      been in culture for over 18 months. The cell line was named HIO615. Western blot
      analysis showed HIO615 expressed HPV16 E6 and E7 protein. HIOC were positive for
      cytokeratin, tonofibril and desmosome as observed by scanning electron
      microscope. The number of large colonies of dense multilayer cells was low
      (0.77%). No tumor developed in nude mice injected subcutaneously with HIOEC.
      CONCLUSION: A human immortalized oral epithelial cell line induced by HPV16E6 and
      E7 has been successfully established.

PMID- 11955352
TI  - [The value of preoperative routine donor leg angiography in free fibula flaps].
AB  - OBJECTIVE: To analyze the value of preoperative routine donor leg angiography in
      free fibula flaps. METHODS: Eighty-nine consecutive potential candidates for free
      fibula reconstruction were reviewed. They were further divided into two groups,
      group one received preoperative routine donor leg angiography, group two received
      only preoperative evaluation of dorsalis pedis and tibial posterior artery and
      without angiography. RESULTS: There were 49 patients in group one and 40 patients
      in group two. In group one, the results of preoperative angiography resulted in a
      change of the surgical plan in two patients. In group two, all the patients
      showed normal dorsilis pedis and tibial posterior artery, and fibula flap was
      harvested without preoperative angiography. One patient in each group showed
      venous deformity during the operation, and flap harvesting was abandoned.
      CONCLUSIONS: Routine preoperative angiography in free fibula flap is unnecessary.
      The following three conditions that require an angiography are: abnormal pedal
      pulses, significant previous lower leg trauma, and suspected vascular diseases.

PMID- 11955354
TI  - [Preliminary analysis about influence of porcelain thickness on interfacial crack
      of PFM].
AB  - OBJECTIVE: This study was about the influence of porcelain thickness on crack at
      interface. METHODS: The effect of porcelain thickness on the flaw at the
      interface between porcelain and metal was studied in three groups with porcelain
      thickness of 0.5 mm, 1.5 mm and 2.5 mm (metal thickness of 0.5 mm) by means of
      moire interferometre and interfacial fracture mechanics. The parameter Jc was
      compared among the three groups and the growing of the flaw was observed.
      RESULTS: Jc and the extreme strength of group with porcelain thickness of 0.5 mm
      (2.813 N/m and 9.979 N) were lower than those of the groups with porcelain
      thickness of 1.5 mm and 2.5 mm (5.395 N/m, 19.134 N and 5.429 N/m, 19.256 N).
      Flaws extend along the interface in the groups with porcelain thickness of 1.5 mm
      and 0.5 mm. CONCLUSIONS: (1) Fracture resistance of the interface in the groups
      with porcelain thickness of 1.5 mm and 2.5 mm is similar and it decreases in the
      group with 0.5 mm thick porcelain. (2) When porcelain is 1.5 mm or 0.5 mm thick,
      flaws will extend along the interface. When porcelain is 2.5 mm thick, flaws will
      extend into the porcelain layer.

PMID- 11955353
TI  - [Experimental study on subcutaneous bone formation by marrow stromal osteoblast
      cancellous bone matrix compound artificial bone].
AB  - OBJECTIVE: To investigate the feasibility of using marrow stromal osteoblast
      (MSO) as bone derived cell and using cancellous bone matrix (CBM) as scaffold for
      bone tissue engineering, the subcutaneous osteogenesis of MSO-CBM compound
      artificial bone (MCCAB) was observed in the experiment. METHODS: The marrow
      stromal cells of adult New Zealand rabbits cultivated and induced in vitro were
      used to form MCCAB by mixing, seeding and solidifying methods assisted by
      alginate. The MCCABs were auto-transplanted subcutaneously into the rabbits for 4
      to 8 weeks. The alginate-cancellous bone matrix composites or the cancellous bone
      matrix alone were implanted as control. The effectiveness of bone formation was
      assessed by means of roentgenography, histology and computerized
      histomorphometry. RESULTS: The osteogenesis of MCCABs was better than that of the
      alginate-cancellous bone matrix composites and of the cancellous bone matrixes.
      In the MCCABs, both intramembranous and cartilaginous osteogeneses were seen but
      the former was obvious. In the control, only slight cartilaginous osteogeneses
      were seen. CONCLUSIONS: The osteogeneses of the MCCABs constructed by using
      tissue engineering method were obvious when transplanted subcutaneously. The MSO
      and CBM can be used as good bone-derived cell and scaffold material respectively
      for tissue-engineered bone construction.

PMID- 11955355
TI  - [Angiographic study of dangerous anastomasis of the external carotid artery].
AB  - OBJECTIVE: To investigate the dangerous anastomasis between the external carotid
      artery and the intracranial arteries. METHODS: Angiograms of the external carotid
      artery in 250 cases were analyzed, including 35 cases of moyamoya and 215 cases
      of head and neck lesions. RESULTS: The 35 cases of moyamoya, 14 middle meningeal
      arteries (MMA) were found to participate in the blood supply of the brain. In
      addition, 11 superficial temporal arteries and 7 occipital arteries supplied the
      brain. All the cases with ligated external carotid artery (ECA) had the pharyngo
      occipital anastomasis. Moreover, the ophthalmic arteries in three cases were
      found to originate from the MMA. CONCLUSIONS: The external carotid artery has a
      variety of anastomasis with the internal carotid artery (ICA) and the vertebral
      artery. Under such circumstances, special measures must be taken to circumvent
      inadvertent intracranial embolization.

PMID- 11955356
TI  - [The angiographic classification and sclerotherapy of cavernous hemangiomas of
      maxilloface].
AB  - OBJECTIVE: To explore the factors that affect the curative effect and the best
      method of treatment for the patients with maxillofacial cavernous hemangiomas.
      METHODS: 102 cases of maxillofacial cavernous hemangiomas were performed DSA
      examination and taken serial photography. According to the diameter, number and
      draining speed of efferent veins of the tumor, the cavernous hemangiomas were
      classified into two types-the high efferent speed and low efferent speed type.
      For all of them, were randomly performed embolization of efferent veins with
      absolute ethanol plus bleomycin-A5 intratumor injection (group I) and bleomycin
      A5 intratumor injection alone (group II). RESULTS: The cure rate and general
      effective rate has significant difference (P < 0.01) between two groups in 70
      patients with high efferent speed veins, while no significant difference (P >
      0.05) in 32 patients with low efferent speed veins. CONCLUSIONS: This new
      classification is beneficial for seeking method of treatment. The embolization of
      efferent veins is an effective method for cavernous hemangioma with high efferent
      speed veins; but for the type with low efferent speed veins, bleomycin-A5
      intratumor injection alone could acquire a good results.

PMID- 11955357
TI  - [Effect of sodium chloride treatment on remineralization of human root dentine
      caries in vitro].
AB  - OBJECTIVE: To investigate the influence of soluble phosphoprotein removal from
      artificial dentin caries lesions by pretreatment of NaCl on subsequent
      remineralization. METHODS: Human root dentin samples were demineralized in an
      acidic gel (pH = 4.4) at 37 degrees C for 48 hours. Samples were pretreated with
      0.5 mol/L NaCl solution and 0.5 mol/L disodium EDTA solution respectively. The
      histomorphologic changes of root caries surface were examined by scannings
      electronic microscope. Mineral profiles were assessed by means of
      microradiography. RESULTS: No histomorphologic changes were present on root
      caries surface after treated with 0.5 mol/L NaCl solution, while many opened
      dentin tubules were seen after treated with 0.5 mol/L disodium EDTA solution. The
      remineralization results showed that pretreatment with 0.5 mol/L NaCl solution
      increased more remineralization than pretreated with 0.5 mol/L disodium EDTA
      solution. CONCLUSION: 0.5 mol/L NaCl solution has no damage on the root caries
      surface. The in vitro results suggested that removal of soluble phosphoprotein
      from dentin lesions is an interesting approach to enhance remineralization.

PMID- 11955358
TI  - [Oral venous lakes: a clinicopathologic analysis of 20 cases].
AB  - OBJECTIVE: To improve the recognization and treatment for oral venous lakes
      (OVL). METHODS: Clinicopathologically analysis of 20 cases of oral venous lakes
      was performed. All the samples were removed by surgically. RESULTS: All the
      lesions occurred in senile persons and located under the mucosa. Among the 20
      cases, 11 were male patients and 9 were female; 18 of 20 occurred in the lower
      lip, another two in the upper lip and buccal mucosa. The lesions were 0.3
      approximately 1.2 cm in size. Pathologically, the oral venous lake was composed
      of single or a few large, dilated and irregular veins. Thrombosis and
      organization were found within the lesions sometimes. CONCLUSIONS: Oral venous
      lakes are a kind of focal anomalies of venous structure. All the 20 cases (with a
      follow-up time from 8 months to 4 years) has no recurrence after surgical
      treatment.

PMID- 11955359
TI  - [Manipulation aided by joint cavity extension followed by occlusal splint for
      treatment of acute anterior disk displacement without reduction].
AB  - OBJECTIVE: To evaluate a new treatment method for temporomandibular joint acute
      disk displacement without reduction. METHODS: Twenty-one patients diagnosed as
      acute anterior disk displacement without reduction were treated by manipulation
      with the aid of joint cavity extension followed by anterior repositioning splint.
      All and eleven of twenty-one patients were re-examined two weeks after insertion
      of splint and at the end of treatment (3 approximately 6 months later). RESULTS:
      (1) Degree of maximum mouth opening was increased from 25.8 mm before treatment
      to 46.6 mm 2 weeks after, 48.1 mm at the end of treatment; (2) Mean pain level
      (VAS) dropped from 2.62 before treatment to 0.43 2 weeks after, 0.18 at the end
      of treatment; (3) Fricton's TMJ dysfunction index and craniomandibular index
      decreased from 0.337 and 0.185 respectively before treatment to 0.021 and 0.011
      respectively 2 weeks after, 0.031 and 0.018 respectively at the end of treatment.
      CONCLUSIONS: The treatment method should be considered for acute anterior disk
      displacement without reduction if medication and physical therapy failed to have
      disk successfully reduced.

PMID- 11955360
TI  - [Proteins in saliva and dental plaque fluid in relation to caries
      susceptibility].
AB  - OBJECTIVE: To investigate the relationship of the levels of proteins in parotid
      saliva, whole saliva and dental plaque fluid with caries susceptibility. METHODS:
      Sixty-six of university students were selected as subjects, 39 in caries-free
      group (CF, DMFS = 0) and 27 in caries-susceptible group (CS, DMFS >/= 8 and DT
      >/= 3). Total protein concentration was detected with Lowry method. Protein
      compositions were separated with SDS-PAGE and alkaline electrophoresis. The gels
      were analyzed using an image evaluation system. RESULTS: Total protein level in
      dental plaque fluid was about 10-fold higher than that in saliva. Whole saliva
      was closely related to dental plaque fluid in terms of proteins only in CF group
      (r = 0.804), but there was little relation in CS group. The proteins that
      occurred in all three fluids were 14 000, 66 000 and 76 000 proteins. The 14 000,
      15 000 and 38 000 proteins level in dental plaque fluid and 14 000 protein level
      in whole saliva were significantly lower in CS group than in CF group.
      CONCLUSIONS: The proteins of dental plaque fluid are influenced significantly by
      whole saliva in CF group. The results suggest some kinds of proteins in dental
      plaque fluid and in whole saliva might play important roles against caries.

PMID- 11955361
TI  - [Influence of post-core on the strength of endodontically treated and crowned
      teeth].
AB  - OBJECTIVE: To investigate the influence of post-core structure on the strength of
      endodontically treated and crowned teeth with or without a 2.0 mm dentine
      ferrule. METHODS: A total of 60 recently extracted human maxillary central
      incisors were endodontically treated and randomly divided into five groups of 12.
      They were given following treatments: Group A, endodontically treated; Group B,
      endodontically treated and crowned (PFM); Group C, cast metal post-core with 2.0
      mm dentine ferrule and crowned (PFM); Group D, cast metal post-core with no
      dentine ferrule and crowned (PFM); Group E, prefabricated post and composite core
      with 2.0 mm dentine ferrule and crowned (PFM). All specimens were stored at 100%
      humidity at room temperature for 30 days before testing. Each specimen was in a
      special jig on the MTS 810 universal material testing machine and subjected to a
      load at a 135-degree angle to the long axis until failure, with crosshead speed
      of 0.02 cm/minute. Analysis of variance followed by the Newman-Keuls pairwise
      multiple comparison tests was used to compare the results. RESULTS: There was a
      statistically significant difference between different restorative methods. The
      cast metal post-core with 2.0 mm dentine ferrule and crowned teeth had the
      highest fracture strength (1793.59 +/- 387.93N), followed by endodontically
      treated intact teeth (1466.68 +/- 240.11N). No significant difference in the
      fracture strength was found among the other three groups (958.49 +/- 286.02N;
      992.98 +/- 291.00N; 994.94 +/- 285.04 N). There was a statistically significant
      difference in the fracture resistance between crowned teeth with and without 2.0
      mm dentine ferrule (P < 0.01). CONCLUSIONS: Not all post-core structure could
      improve the strength of endodontically treated teeth. The dentine ferrule can
      effectively improve the fracture resistance of endodontically treated and crowned
      teeth.

PMID- 11955362
TI  - [Expression of bone sialoprotein and osteopontin in developing dental tissues of
      rats].
AB  - OBJECTIVE: To investigate the timing and location of the expression of bone
      sialoprotein (BSP) and osteopontin (OPN) in developing dental tissues of rats.
      METHODS: Every three neonatal rats were sacrificed at day 1, weeks 1, 2, 3, 5 and
      8. The mandibles were dissected and the first molar and the surrounding tissue
      were fixed, then demineralized with 15% EDTA. Immunohistochemical technique was
      used to determine the expression of BSP and OPN in dental tissues and the
      surrounding bone at different time points. RESULTS: Immunoreactivitis of BSP and
      OPN were present in matured ameloblasts, dentinoblasts, cementoblasts,
      osteoblasts, and the matrix. The expression of BSP and OPN in cementum and
      alveolar bone was stronger than that in enamel and dentine. In cementum and
      alveolar bone, BSP appeared to be concentrated in unmineralized and mineralized
      tissues, but OPN was concentrated in the mineralizing frontier and reversal line.
      CONCLUSIONS: BSP and OPN play an important role in the development and
      mineralization of rat mineralized tissues. The expression of BSP was different
      from OPN, indicating their different functions.

PMID- 11955363
TI  - [Experimental study of the influence of mandibular distraction osteogenesis on
      inferior alveolar nerve function].
AB  - OBJECTIVE: To evaluate the influence of mandibular distraction osteogenesis on
      inferior alveolar nerve function. METHODS: 16 young Macaca rhesus monkeys were
      used as experiment animals. 5 days after mandibular osteotomy under general
      anesthesia, 10 male monkeys were distracted at right side and 6 females were
      bilaterally distracted at a rate of 0.5 mm x 2/day, for 15 days. The mandible was
      lengthened to an average of 13.5 mm. The Sensory Nerve Action Potential (SNAP)
      test was successfully applied in 16 monkeys before operation and at 0, 2, 4, 6, 9
      and 12 weeks after distraction finished. Eight-channel EMG equipment was used for
      SNAP wave recording. The recordings were made with needle electrodes at foramen
      ovale and the stimulation was done at the mental foramen with two surface
      electrodes. The metal ground electrode was fixed on the right forearm. The
      stimulation intensities were five times of thresholds of each animal. The latency
      was measured at the first wave peak and the amplitude was measured between two
      wave peaks. RESULTS: Just after distraction finished, the latency period was
      22.18% longer than before operation and gradually shortened as time lapsed. When
      distraction finished, the amplitude of SNAP wave was only 28.54% of that before
      operation, and after 12 weeks, it increased to the level of 99.84% of that before
      operation. CONCLUSIONS: The mandibular distraction osteogenesis has temporary
      influence on the function of inferior alveolar nerve, but it is little and
      reversible, along with the regeneration of nerve sheath and axon, the nerve
      function can gradually return to normal level.

PMID- 11955364
TI  - [Expression of IL-6 and it's mRNA transcription in the process of rat
      periodontium remodeling influenced by various bite forces].
AB  - OBJECTIVE: To study the expression of IL-6 in periodontal ligament fibroblasts
      (PLF) and osteoblasts in order to explain the molecular mechanism of the bite
      forte on periodontium remodeling. METHODS: A rat model of different bite forces
      was established to study the expression of IL-6 and IL-6 mRNA in the PLF and
      osteoblasts with immunohistochemical (IHC) and in situ hybridization (ISH)
      techniques. RESULTS: In the group of disuse bite force, the expression of IL-6
      and IL-6 mRNA in the PLF and osteoblasts enhanced apparently compared with that
      in the group of normal bite force. The gray level values enhanced respectively
      from 6.5886 +/- 1.6 to 38.8381 +/- 9.5 and from 11.8337 +/- 2.8 to 57.2623 +/-
      13.6. The loosely arrangement of periodontal fibers and the resorption of
      alveolar bone were observed in histological study. In the group of compensation
      bite force, the same result was observed with IHC and ISH, the gray level values
      enhanced respectively from 6.3119 +/- 1.5 to 45.5456 +/- 11.1 and from 11.7714 +/
      2.8 to 81.9391 +/- 19.5, but the increase of periodontal fibers, the resorption
      and formation of alveolar bone were observed simultaneity in histological study.
      CONCLUSIONS: With the change of bite force, the expression of IL-6 and IL-6 mRNA
      in PLF and osteoblasts presents a certain regulation. IL-6 may play important
      roles in the effect of bite force on periodontium remodeling.

PMID- 11955365
TI  - [The effects of insulin-like growth factor-II on the proliferation of osteoblast
      like cells in vitro].
AB  - OBJECTIVE: To seek for the appropriate concentration, at which IGF-II can exerts
      its strong effects on postirradiation proliferation, physiological function and
      differentiation of the rat's osteoblast-like cells (ROB). METHODS: The osteoblast
      like cells used were isolated from the calvariae of neonatal (one-day-old) SD
      rats by sequential enzymatic digestion. The third passages of the cells were
      irradiated with gamma-ray from a (60)Co source at the doses of 100, 400, 600, and
      900 cGy. The medium was changed immediately after irradiation and 5
      concentrations of IGF-II, i.e., 0, 0.1, 1.0, 10.0, and 100.0 microgram/L were
      added. 6 days after radiation (9 days in culture), the examination, or the
      measurement of relative cell number, was carried out. RESULTS: Radiation
      inhibited the ROB, even lethally. IGF-II completely counteracted the inhibitory
      effects when the cells were exposed to the radiation at lower dose (100 cGy), and
      partially when at higher dose (400 cGy). But after the radiation at much higher
      dose as 900 cGy, the damages were irreversible, even with the existence of this
      growth factor. CONCLUSIONS: At least a portion of effective recovery of
      postirradiation damages may be due to IGF-II-induced radioresistance. Incubation
      with IGF-II can increase radioresistance or repair of radiation-induced cells
      damages. However, this effect depends on the dose of radiation.

PMID- 11955366
TI  - [Proliferating activity and differentiation between peripheral cells and central
      cells in ameloblastoma].
AB  - OBJECTIVE: To investigate the proliferating activities and differentiation
      between peripheral cells and central cells in ameloblastoma. METHODS: Expressions
      of proliferating cell nuclear antigen (PCNA), Ki-67, CK10&13 and CK19 were
      detected in 43 ameloblastoma (15 follicular, 20 plexiform and 8 acanthomatous) by
      SP immunohistochemical methods. RESULTS: The PCNA labelling indices were
      significantly higher in peripheral cells (5.12% +/- 2.76%) of tumour nests or
      strands than in central cells (1.36% +/- 1.02%, P < 0.001). The peripheral cells
      of tumour nests or strands exhibited a significantly higher Ki-67 labelling index
      (3.63% +/- 1.80%) than central cells (1.26% +/- 0.96%, P < 0.001). The labelling
      indices between PCNA and Ki-67 showed a significant correlation (P < 0.01). The
      positive expressions of CK10&13 and CK19 were significantly higher in central
      cells than in peripheral cells (P < 0.01). CONCLUSIONS: The peripheral zones of
      tumour nests or strands are regarded as proliferating areas; there exists a
      significantly different differentiation between central cells and peripheral
      cells.

PMID- 11955367
TI  - [Expression of apoptosis-related protein in epithelial dysplasia and squamous
      cell carcinoma].
AB  - OBJECTIVE: To study the expression and significance of apoptosis-related protein
      p53, Bcl-2, and Bax during the development of oral squamous cell carcinoma (SCC).
      METHODS: The expression was observed in 10 normal oral epithelia, 48 dysplasia
      epithelia and 42 SCC by immunohistochemical evaluation. RESULTS: In normal
      mucosa, the positive rate of p53, Bcl-2 and Bax were 0%, 20% and 60%. In
      dysplasia epithelia, the positive rate of p53 is increased (P < 0.05), the
      positive rate of Bcl-2 and Bax remained no significant change (P > 0.05), but the
      positive intensity in severe dysplasia was higher than in mild group. In SCC, the
      positive rate of Bcl-2 increased significantly (compared with dysplasia, P <
      0.05), while the expression of Bax was decreased with the increase of SCC
      histological grade. Further analysis showed the correlation was evident in p53
      and Bax in dysplasia, and in p53 and Bcl-2 in SCC. CONCLUSIONS: In dysplasia, p53
      gene mutation results in accumulation of dysplasia cells. In SCC, the cooperation
      of p53, Bcl-2 and Bax results in the progression of SCC. Apoptosis genes could
      work either independently or cooperatively.

PMID- 11955368
TI  - [Interface bond and compatibility between GI-II glass/alumina composite and
      Vitadur alpha veneering porcelain].
AB  - OBJECTIVE: Multiple layer techniques were commonly employed in fabricating all
      ceramic restorations. Bond and compatibility between layers were vitally
      important for the clinical success of the restorations. The purposes of this
      study were to investigate the bond of the interface between the GI-II
      glass/alumina composite and Vitadur alpha veneering porcelain, and to study the
      thermal compatibility between them. METHODS: Prepared a bar shaped specimen of GI
      II glass/alumina composite 25 mm x 5 mm x 1 mm in size, with bottom surface pre
      notched. The upper surface was veneered with Vitadur alpha veneering porcelain
      (0.2 mm opaque dentin and 0.6 mm dentin porcelain), then fractured and the
      fracture surface were examined under scanning electron microscope (SEM) and
      electron microprobe analyzer (EMPA) with electron beam of 10 micrometer in
      diameter; ten all-ceramic single crowns for an upper right central incisor were
      fabricated and the temperatures of thermal shock resistance were tested. RESULTS:
      SEM observation showed tight bond between the composite and the porcelain; The
      results of EMPA showed that penetration of Na, Al elements from glass/alumina
      into veneering porcelain and Si, K, Ca elements from veneering porcelain into
      glass/alumina occurred after sintering baking; The temperature of thermal shock
      resistance for anterior crowns in this study was 158 +/- 10.3 degrees C, cracks
      were mainly distributed in veneering porcelain with thicker layer. CONCLUSIONS:
      Chemical bond exists between the GI-II glass/alumina composite and Vitadur alpha
      veneering porcelain, and there is good thermal compatibility between them.

PMID- 11955369
TI  - [Expression of mitogen-activated protein kinase and its upstream regulated signal
      in human hepatocellular carcinoma].
AB  - OBJECTIVE: To detect protein expression of ERK(1), ERK(2), JNK(1), p38 and
      MEK(1), MEK(2) in human hepatocellular carcinoma and adjacent non-neoplastic
      liver. METHODS: In 16 surgically resected hepatocellular carcinoma and para
      carcinoma tissues, Western blotting was used to detect expression of ERK(1),
      ERK(2), JNK(1), p38 and MEK(1), MEK(2). RESULTS: In all cases, ERK(1), ERK(2),
      p38 expression in hepatocellular carcinoma was significantly higher than that in
      para-carcinoma: integral optic density (IOD) of ERK(1) was 300 +/- 98 in
      carcinoma and 98 +/- 48 in para-carcinoma tissues (t = 2.519, P < 0.01); IOD of
      ERK(2) was 587 +/- 83 in carcinoma and 232 +/- 96 in para-carcinoma tissues (t =
      2.745, P < 0.01); IOD of p38 was 270 +/- 85 in carcinoma and 107 +/- 88 in para
      carcinoma tissues (t = 2.491, P < 0.01). JNK(1) expression in hepatocellular
      carcinoma was significantly lower than that in para-carcinoma; IOD of JNK(1) was
      111 +/- 93 in carcinoma and 292 +/- 109 in para-carcinoma tissues (t = 2.473, P <
      0.01). Protein levels of MEK(1) and MEK(2) in carcinoma were significantly higher
      than in para-carcinoma. IOD of MEK(1) was 1 418 +/- 244 in carcinoma and 806 +/-
      90 in para-carcinoma tissues (t = 2.546, P < 0.01). IOD of MEK(2) was 1 041 +/-
      122 in carcinoma and 468 +/- 40 in para-carcinoma tissues (t = 2.861, P < 0.01).
      CONCLUSIONS: ERK(1), ERK(2), MEK(1) and MEK(2) in the signal transduction pathway
      for cell proliferation are significantly overexpressed and the expression of
      JNK(1) is lower in hepatocellular carcinoma. Their unbalance is one of the
      important reasons for the over growth and infinite proliferation of the
      hepatocellular carcinoma cell. The p38 and JNK(1) may be activated by different
      pathway.

PMID- 11955370
TI  - [Change of gene expression of transforming growth factor-beta1, Smad 2 and Smad 3
      in hypertrophic scars skins].
AB  - OBJECTIVE: To explore the regulatory mechanisms of transforming growth factor
      beta1 (TGF-beta1) and two transcriptional factors Smad 2, 3 on hypertrophic scar
      formation and fetal scarless healing. METHODS: Thirty-two cases were detected to
      compare the gene expression of TGF-beta1, Smad 2 and Smad 3 with RT-PCR. Among
      those cases, there were 8 cases of hypertrophic scars, 8 cases of control skins,
      8 cases of fetal skins and 8 cases of adult skins. RESULTS: TGF-beta1, Smad 2 and
      Smad 3 gene expression could all be detected in hypertrophic scars, fetal and
      adult skins. Among 8 groups examinated in this experiment (each group comprised a
      hypertrophic scar and its corresponding normal skin), there were 5, 8 and 5
      groups in which TGF-beta1, Smad 2 and Smad 3 gene expression were higher in
      hypertrophic scars than in normal skins respectively. The fetal skins showed
      significantly lower level of TGF-beta1 and Smad 3 gene expression compared with
      adult skins (t = 2.204, P < 0.05 and t = 4.269, P < 0.01 respectively), while
      mRNA contents of Smad 2 were obviously higher in fetal skins than in adult skins
      (t = 6.685, P < 0.01). CONCLUSION: TGF-beta1 and its downstream signal molecules
      Smad 2, Smad 3 might be involved in hypertrophic scar formation. Higher gene
      expression of TGF-beta1, Smad 2 and Smad 3 in hypertrophic scars might lead to
      stimulating extracellular matrix deposition, inducing fibroblast proliferation
      and accelerating fibrogenesis. Lower mRNA contents of TGF-beta1 and Smad 3 in
      fetal skins compared with adult skins might be associated with fetal scarless
      healing.

PMID- 11955371
TI  - [The study for the hemodynamics of expansive skin and the transplant time of skin
      flap designed by expansive skin].
AB  - OBJECTIVE: To study the change rule of the hemodynamics of expanded skins and
      research the transplant time of random-pattern flaps that are made of the
      expanded skin. METHODS: 72 ears of 64 rabbits were used as a subject of
      experiment. Four items of the contrasted skin (n = 8) and expanded skin (n = 8 x
      8), Which include the microvessel diameter, the microvessel density, the blood
      velocity and the blood volume, were observed and measured by the microcirculatory
      imaging computer analysis system, the enzyme histochemical dyeing and the more
      functions colored pathological imaging computer analysis system. The length 
      width proportion and the largest area of the flaps that had made of the expansive
      skin and survived were measured. RESULTS: (1) The four items of expanded skin,
      that the microvessel diameter, the microvessel density, the blood velocity and
      the blood volume are 13.43 +/- 0.98 micrometer, 0.0472 +/- 0.0022, 1012.70 +/-
      65.51 micrometer/s, 14.71 +/- 0.74 micrometer(3)/s respectively, are much bigger
      or quicker than those of contrasted skin [(7.22 +/- 0.71) micrometer, 0.0108 +/-
      0.0002, (327.01 +/- 65.51) micrometer/s, (1.46 +/- 0.41) micrometer(3)/s] and
      there is the significant difference between both (6.49 < t < 49.49, P < 0.01).
      (2) The blood velocity increases in the expanding phases and always keeps on
      higher level. The other items all change periodically. Span of the period is four
      weeks. The microvessel diameter and the blood volume have a peak value at third
      weekend of every period and in the later period enhance more on the basis of the
      former period. The microvessel density changes in definite range in every period.
      (3) The surviving area of the random skin flaps is the largest which were made of
      the expanded skin in third weekend of every period, it changes more than those of
      other weekends in same period and later period is superior to the former period.
      There is a significant difference compared with contrasted random skin flaps (q =
      3.7215, P < 0.05; q = 5.5026, P < 0.01). CONCLUSION: The hemodynamics of the
      expanded skin changes periodically in expansive course. The time of peak value of
      the blood volume is the best opportunity that random-pattern skin flaps are made
      of the expanded skin in every period.

PMID- 11955372
TI  - [Repair of porcine full-thickness skin defects with autologous tissue engineered
      skin].
AB  - OBJECTIVE: To explore a feasible method to repair full-thickness skin defects
      with tissue engineered techniques. METHODS: The skin specimens were cut from the
      Changfeng hybrid swines' abdomen, then keratinocytes and fibroblasts were
      isolated and harvested by trypsin, EDTA and type II collagenase. The cells were
      seeded in petri dishes for primary culture. When the cells were in logarithmic
      growth phase, they were treated with dispase II (keratinocytes) or trypsin
      (fibroblasts) to separate them from the floor of the tissue culture dishes. A
      biodegradable material-pluronic F-127 was prefabricated and mixed with these
      cells, and then the cells-pluronic compounds were seeded evenly into polyglycolic
      acid (PGA). Tinally the constructs were replanted to autologous animals to repair
      full-thickness skin defects. Histological changes were observed in 1, 2, 4 and 8
      weeks postsurgery. RESULTS: The cells-pluronic F-127-PGA compounds could repair
      autologous full-thickness skin defects. Histologically, the tissue engineered
      skin was similar to normal skin with stratified epidermis overlying a moderately
      thick collageneous dermis. CONCLUSION: Tissue engineered skin can repair
      autologous full-thickness skin defects with primary-cultured keratinocytes and
      fibroblasts as seed cells and PGA as a cell carrier.

PMID- 11955373
TI  - [Effect of triton X-100 on preparing porcine thoracic aortas acellular matrix].
AB  - OBJECTIVES: To investigate the method of preparing porcine thoracic aortas
      acellular tissue matrix (ACTM) by trypsin, EDTA and Triton X-100 and to find the
      best concentration of X-100. METHODS: A total of 56 roots of fresh thoracic
      aortas (without adventitial tissue) from 80 kg-100 kg tame pigs were divided
      randomly into > groups, each containing 8 roots. Every vessel was put into a 50
      ml centrifugal tube with a solution of 0.1% trypsin + 0.02EDTA in PBS for 24 h.
      After that, each group was separately immerged into a solution of 0.1%, 0.2%,
      0.5%, 1.0%, 2.0%, 5.0%, 10.0% Triton X-100 for 144 h-240 h. Specimens were taken
      every 6 h. Specimens were stained with haematoxylin-eosin and observed grossly
      under the light and transmission electron microscopy. RESULTS: Light and
      transmission electron microscopy revealed that ACTM was composed of insoluble
      collagen, elastin, and some insoluble metamorphic organelles. The best
      concentration of Triton X-100 was 1% at the time of 176.25 h +/- 5.5 h.
      CONCLUSIONS: Porcine thoracic aortas ACTM can be obtained successfully through
      this procedure. Triton X-100 is a good reagent for preparing vessel ACTM.

PMID- 11955375
TI  - [Color Doppler ultrasonographic assessment of the risk of injury to major branch
      of the middle hepatic vein during laparoscopic cholecystectomy].
AB  - OBJECTIVE: To investigate the cause of hemorrhage from the gallbladder bed during
      laparoscopic cholecystectomy. METHODS: Color Doppler ultrasound was used to
      examine the cause of venous hemorrhage from the gallbladder bed during
      laparoscopic cholecystectomy in 1 patient postoperatively and to examine the
      anatomic relationship between the gallbladder bed and branches of the middle
      hepatic vein in 91 patients preoperatively. RESULTS: There is a major branch of
      middle hepatic vein extended close to the gallbladder bed. The branch of the
      middle hepatic vein was completely adherent to the gallbladder bed in 14 of 91
      patients (15.4%). The mean distance between the closest point of the middle
      hepatic vein and the gallbladder bed is 5.0 +/- 4.6 mm, the mean diameter of this
      point is 3.2 +/- 1.1 mm. CONCLUSIONS: Patients with large branches of the middle
      hepatic vein close to the gallbladder bed are at risk of hemorrhage during
      laparoscopic cholecystectomy and should be identified preoperatively with
      ultrasound.

PMID- 11955374
TI  - [The autotransplanted tracheas wrapped in united muscle flap of the neck: an
      experiment].
AB  - OBJECTIVE: To investigate the way of revascularization of donator's trachea
      wrapped in united muscle flap. METHODS: Using fiberoptic bronchoscopy,
      histopathology and microangiography, we evaluated the tracheal mucosal blood
      flow, the survival rate, the percentage of patency, and the graft viability of
      autograft tracheas with varying lengths wrapped in one-sided sternocephalic
      muscle flap and two-sided sternohyoid-sternothyroid muscle flap and autograft
      tracheas with the length of 5 rings without wrapped in muscle flap in 32 dogs.
      RESULTS: In the tracheal autograft wrapped in the united muscle flap group with a
      length less than 4 centimeters, the submucosal blood flow of graft could be
      detected by laser blood flowmetry one week after transplantation, and it reached
      60% of the normal, which had no significant difference between the place near the
      site of anastomosis and the middle part of the graft. Dense vessels could be
      found to grow from the wrapped muscles into the autografted trachea by
      microangiography. Histopathological examination demonstrated that the structure
      of the autograft was the same as what it originally was. the inner surface of the
      autograft was covered with pseudostratified columnar ciliary epithelia, and no
      necrotic tracheal cartilages were found. Every autograft could survive over long
      time. However, at 1 week, most mucous membrane in the middle part of the graft
      with length over 4 cm was in gray or in pale; hyperemia, edema, and haemorrhage
      were found near the site of anastomosis. Mucosal blood flow measured by laser
      blood flowmetry in the middle part of the graft was significantly less than that
      near the site of anastomosis. Malacia, dissolution or granulation hyperplasia
      occurred in midportion of the major grafts shortly after transplanatation. As for
      those autografted trachea without wrapping in muscles flap, mucous membranes
      turned black one week after the transplantation and all dogs died of graft
      necrosis later. CONCLUSION: One-sided sternocephalic muscle flap and two-sided
      sternohyoid-sternothyroid muscle flap can provide blood for the graft and the
      grafted trachea can survive for a long time.

PMID- 11955376
TI  - [Super-selective pump-insertion into the target artery and regional intraarterial
      infusion chemotherapeutant and immunizator in treatment of the latter
      gastrointestinal cancer].
AB  - OBJECTIVE: To evaluate the effect of operative selective pump-insertion into the
      tumorous target artery, postoperative regional infusion chemotherapeutant and
      immunizator for treatment the latter gastrointestinal cancer. METHODS: The effect
      of operative super-selective pump-insertion into the tumorous nutritious artery,
      postoperative regional infusion chemotherapeutant and immunizator for treatment
      88 cases patients suffering from irremovable gastrointestinal cancer was
      observed. Of them, 45 cases were gastric cancer, 31 cases were rectal cancer,
      11cases were colic cancer. RESULTS: Complete response 2 case; Part response 77
      cases, 11 cases patients had received secondary resection after intraarterial
      chemotherapy. Non chang 9 cases; effective rates reach to 89.8%. One, two and
      three years survival rates were 86.4%, 30.7% and 10.2%. Average survival period
      were 21.5 mouths. CONCLUSION: Super-selective pump-insertion into the artery and
      regional intraarterial chemotherapy is an efficient way in treatment of the
      latter gastrointestinal cancer, which can delay the survival period of patients
      with tumor, and increase the resectable rate.

PMID- 11955377
TI  - [Colonoscopy in preoperative staging and treatment of colorectal cancer].
AB  - OBJECTIVES: To investigate the value of colonoscopy for the diagnosis and
      preoperative staging of colorectal cancer, and evaluate the significance of
      correct preoperative staging in guiding treatment. METHODS: 28 patients with
      colorectal cancer were examined by general colonoscopy, magnifying endoscopy and
      endoscopic ultrasonography before operation. Preoperative staging, and proper
      treatment protocols were made. RESULTS: Endoscopy revealed that 15 of the 28
      patients had early colorectal cancer and 13 advanced colorectal cancer. The
      correct diagnosis rate for preoperative staging was 100%; the accuracy of
      penetrating depth was 89% (25/28). In the early cases, tumour invasion was
      confined to mucosal layer in 11 patients and submucosal layer in 4. Six patients
      with early cancers 6 cm from the anus were treated by endoscopic mucosa resection
      (EMR) or EMR combined with open surgery. No postoperative recurrence was found by
      endoscopy during the period of follow-up for 12 - 40 months. CONCLUSION: Correct
      preoperative staging for colorectal cancer is of important significance in
      guiding treatment, especially in early staging cases. In order to improve the
      quality of life for colorectal cancer patients, we should treat them with
      individualized operation based on curative resection.

PMID- 11955378
TI  - [Surgical treatment of benign ulcer of the gastric cardia: an experience from 21
      cases].
AB  - OBJECTIVE: To study the result of surgical treatment of benign ulcer of the
      gastric cardia. METHODS: Clinical symptom, number, position and size of ulcer,
      preoperative X-ray gastroscopic examine, type and complication of operation were
      retrospective analyzed in 21 patients with benign ulcer of the gastric cardia.
      RESULTS: Average age in 21 patients was 60. Ulcer complicated bleeding in 7 cases
      (33.3%) and perforation in 5 cases (23.8%). Diagnostic rate of preoperative X-ray
      and gastroscopic examine was 57.1% and 100%, respectively. Of 21 patients 18
      (85.7%) were treated by upper partial gastrectomy, and 3 (14.3%) by total
      gastrectomy. All were not operative death and anastomotic leak. CONCLUSIONS:
      upper partial gastrectomy can resect focus of ulcer and decrease secretion of
      stomach acid. It is a simple and ideal pattern of operation for patients with
      benign ulcer of the gastric cardia.

PMID- 11955379
TI  - [Mediastinoscopy in 165 patients].
AB  - OBJECTIVE: To investigate the value of mediastinoscopy in diagnosis of the
      thoracic diseases and the determination of the operative indication. METHODS:
      From 1979 to 2000, 165 patients were given mediastinoscopy by local infiltration
      anesthesia (rare cases with additional vein bacic anesthesia). The exploration
      and biopsy were given to the neoplasms and lymph nodes around the trachea through
      the pretracheal interstice. RESULTS: The diagnosis of 125 patients by
      mediastinoscopy accorded with the pathological diagnosis and that of 21 patients
      was not accorded with the pathology. The rate of definitive diagnosis was 85.6%
      (125/146). The other 19 cases were not included into the ground because 11 cases
      were not given definitive diagnosis and 8 cases with lung cancer were not be
      performed operation although the results of mediastinoscopy were negative. Twenty
      patients with lung cancer which had metastasis in the mediastium and 7 patients
      with malignant lymphadenoma avoided exploratory thoracotomy. CONCLUSION: The
      mediastinoscopy is a effective examinative method to the disease involving the
      lymph nodes in the mediastinum and the thoracic disease closing on the
      mediastinum. The mediastinoscopy in appropriate especially to the simple
      enlargement of lymph node in the mediastinum that is not given definitive
      diagnosis. The cases with lung cancer accompanied enlargement of lymph node in
      the mediastinum and that with tumors in the mediastinum may choose the
      mediastinoscopy.

PMID- 11955380
TI  - [Giant left atrium combined with mitral valvular disease: morphologic
      classification and its clinical significance].
AB  - OBJECTIVE: To study the morphologic classification and its clinical significance
      of giant left atrium (GLA) combined with mitral valvular disease. METHODS:
      Between January 1993 and December 1999, a total of 62 consecutive patients with
      mitral valvular disease, whose preoperative left atrial endodiastolic volume
      index >/= 300 ml/m(2) or endosystolic diameter >/= 6.0 cm, were enrolled as
      research candidates. Morphologically, GLA was classified by Q Hierarchical
      cluster analysis according to the right or left side cardiothoracic ratio of the
      left atrium (r- or l-LATR) on an anteroposterior chest roentgenogram and the
      ratio of the distant diameter of the left main bronchus to the approximate
      diameter of the left main bronchus (LBDd/Dp) or to the trachea (LB/TR) on an left
      anterior oblique chest roentgenogram. RESULTS: According to r-LATR and l-LATR,
      the morphology of GLA was classified clinically into three types: type L (l-LATR
      >/= 0.6 and r-LATR < 0.58), type R (r-LATR >/= 0.58 and l-LATR < 0.6) and type B
      (r-LATR >/= 0.58 and l-LATR >/= 0.6). According to LBDd/Dp and LB/TR, GLA in type
      L and B was further classified into two subtypes, respectively: left posterior
      downward type (L(I) and B(I)), in which LBDd/Dp is equal or exceeds 0.38 or LB/TR
      is equal or exceeds 0.33, and left posterior upward type (L(II) and B(II)), in
      which LBDd/Dp is less than 0.38 or LB/TR less than 0.33. CONCLUSION: The
      morphologic classification of GLA may represent the main pathophysiological
      changes of GLA and might be a guideline for the selection of the optimal
      plication procedures of GLA in patients with valve diseases.

PMID- 11955381
TI  - [Upper thoracic short angular kyphosis: a clinical analysis of 15 cases].
AB  - OBJECTIVE: To provide reference for correct clinical treatment by summarizing the
      characteristics and surgical experience in spinal deformity of the upper thoracic
      (T(1)-T(4)) short angular kyphosis. METHODS: Medical history was taken in 15
      cases are reviewed. The results of X-ray and MRI examinations were analyzed. The
      kyphotic angles were measured using the Cobb technique. All cases underwent the
      anterior spinal cord decompression, by posterolateral approach in 4 cases and
      posterior in 11 cases. RESULTS: Kyphosis was congenital in 7 cases and due to
      tuberculosis approach in 8 was. The average age at deformity was first noted was
      3.6 years in 7 congenital cases and 9.0 years in 8 tuberculosis cases. All cases
      had neurologic deficits. The mean kyphosis was 86.5 degrees (range, 45 - 100
      degrees). The delay between first observation of the deformity and subsequent
      neurologic loss was 16.5 years and 18.1 years respectively. The operation failed
      in 1 case. 13 cases were followed up, with an average 42 months. Seven cases
      showed improvement, 2 no change and 4 deterioration in neurologic deficit.
      CONCLUSIONS: In cases of or tuberculosis kyphosis, the usual time for kyphosis to
      occur is during the preadolescent growth spurt. Neurologic deficits may occur
      without treatment and will be always progressive. The result of operation is not
      satisfactory. Early diagnosis and adequate management of kyphosis will prevent
      progression and thus any possible spinal cord compression. Early fusion is
      usually necessary to control the kyphosis.

PMID- 11955382
TI  - [Measurement of fracture malrotation after interlocking intramedullary nailing of
      femoral shaft fracture].
AB  - OBJECTIVE: To study the quantitative measurement of the extent of malrotation
      after interlocking intramedullary nailing of femoral shaft fracture. METHOD: CT
      scan ("routine method") applied in 36 femoral shaft fractures that had been
      treated with close reduction and interlocking intramedullary nailing. For the
      judgement of the extent of malrotation, the anteversion of both fracture side and
      contralateral side were measured and the difference between the 2 sides was
      evaluated. The increase of anteversion represented internal rotation of the
      distal fragment, whereas the decrease of anteversion represented external
      rotation. RESULTS: The maximum anteversion of the fracture sides, whereas 48
      degrees, the minimum anteversion -10 degrees, the mean value, 15.04 degrees, and
      the standard error is 11.34 degrees. The maximum anteversion of the contralateral
      side, whereas 31.3 degrees, minimum -4.8 degrees, the mean value was 13.96
      degrees and the standard error was 10.20 degrees (P < 0.001). Compared with the
      contralateral side, half of the 36 cases showed increased anteversion and the
      other half decreased anteversion. The mean value of internal rotation is 11.56
      degrees, and external rotation 9.39 degrees. The maximum internal rotation was 37
      degrees, the minimum 0.9 degrees. Eight cases had internal rotation less than 8
      degrees, 6 between 10 degrees - 15 degrees, and 4 over 15 degrees. The maximum
      external rotation was 24.3 degrees, and the minimum 1.8 degrees. Eleven cases had
      external rotation less than 10 degrees, 4 between 10 degrees - 15 degrees and 3
      over 15 degrees. The incidence of malrotation more than 10 degrees was 47%
      (17/36), and more than 15 degrees 19.4% (7/36). CONCLUSION: The incidence of
      malrotation after femoral shaft fracture treated with close reduction and
      interlocking intramedullary nailing is high. Attention should be paid to clinical
      management and strict control for rotational reduction intra-operatively.

PMID- 11955383
TI  - [Inhibition of growth and metastasis of human gastric cancer implanted in nude
      mice by the angiogenesis inhibitor endostatin].
AB  - OBJECTIVE: To study the effects of angiogenesis inhibitor endostatin on the
      growth and metastasis of gastric cancer in vivo. METHODS: Metastatic model
      simulating human gastric cancer was established by orthotopic implantation of
      histologically intact human tumor tissue into gastric wall of nude mice.
      Endostatin was administered sc at dose of 0 mg/kg, 2.5 mg/kg, 10.0 mg/kg and 20.0
      mg/kg every other day for seven weeks. Eight weeks after implantation, the tumor
      size and inhibition rates and intratumoral microvessel density (MVD) and
      apoptotic index (AI) and the presence of metastasis are evaluated respectively
      after the mice were sacrificed. RESULTS: Compared with the untreated controls,
      growth of the orthotopically implanted tumor was significantly reduced in size in
      mice treated with endostatin with an inhibition rate 0, 62.7%, 95.8% and 99.9% at
      the dosage of 0 mg/kg, 2.5 mg/kg, 10.0 mg/kg, and 20.0 mg/kg, respectively. The
      MVD was also decreased significantly in the treated mice [(13.7 +/- 3.90) versus
      (5.73 +/- 2.36), (2.17 +/- 1.28) and (0.66 +/- 0.25)]. The AI was increased
      significantly in the treated mice [(3.91 +/- 2.58)%, versus (6.76 +/- 5.03)%,
      (18.92 +/- 6.75)% and (28.57 +/- 10.34)%]. The incidences of peritoneal
      metastases was also significantly inhibited in the treated mice (87.1% versus
      54.5%, 16.7% and 0). The incidences of liver metastases was also significantly
      inhibited in the treated mice (83.9% versus 27.3%, 8.3% and 0). The growth and
      metastasis of human gastric cancer implanted in nude mice were significantly
      inhibited in a dose-dependent manner (P < 0.05). CONCLUSIONS: Angiogenesis
      inhibitor endostatin can induce apoptosis in gastric cancer by inhibiting tumor
      angiogenesis and has strong inhibitory effect both on tumor growth and metastasis
      of human gastric cancer implanted in nude mice.

PMID- 11955384
TI  - [Surgical management of dumbbell-shaped trigeminal neurinomas].
AB  - OBJECTIVE: To investigate the best surgical approach for the removal of dumbbell
      shaped trigeminal neurinomas (DSTNs). METHODS: The clinical materials of 46
      patients with DSTNs surgically treated were analysed retrospectively. The
      patients were divided into two groups. In the early group (1978 - 1984), a series
      of conventional intradural approaches were used, and in the late group (1985 -
      2000), an epidural approach via the skull-base craniotomy was used. RESULTS:
      Total tumor removal was achieved in 42% (5/12) of the early group and 85% (29/34)
      of the late group (chi(2) = 8.8, P < 0.01). Temporary and permanent cranial nerve
      morbidities were 63% and 47% (chi(2) = 3.4, P > 0.05) in the early group and 48%
      and 15% in the late group (chi(2) = 6.1, P < 0.05). CONCLUSION: The best
      microsurgical approach for the removal of DSTNs is epiduro-transduro
      transtentorial approach via skull-base craniotomy. It is not necessary to resect
      the petrous apex.

PMID- 11955385
TI  - [Direct transsphenoidal pituitary adenoma resection under endoscope].
AB  - OBJECTIVE: To discuss the primary experience and possibility of direct
      transsphenoidal pituitary adenoma resection under endoscopic assistance. METHODS:
      From March 2000 to March 2001, 22 patients with pituitary adenoma were treated by
      direct transsphenoidal pituitary adenoma surgery under endoscope. During direct
      transsphenoidal approach, no incision of the nasal mucosa was made without the
      dissection of the nasal septum and median nasal conchae. Under endoscopic
      assistance, the anterior wall of the sphnoidal sinus and sellae base was opened
      directly and adenoma resection was performed. RESULTS: All the patients were
      followed up for 1 approximately 12 months. The increased hormone level in 17
      patients were decreased to normal postoperatively. By postoperative MRI
      detection, adenomas in 15 patients were removed completely, but part of the
      adenomas were left in the carvernous sinuses in 7 patients. Temporary diabetes
      insipidus was observed in 4 patients. CONCLUSIONS: The direct transsphenoidal
      approach in pituitary adenoma resection under endoscopic assistance is time
      saving, and safe, with good exposure of operative field. The injury to the
      patient and postoperative reaction are less. The effects were satisfactory
      without severe complications.

PMID- 11955386
TI  - [Transmaxillary approach for surgical removal of the invasive skull base tumors].
AB  - OBJECTIVE: To investigate the capable use of transmaxillary approach for surgical
      removal of invasive skull base tumors, the indications and the key points of this
      approach. METHODS: From November 1998 to July 2001, 27 consecutive patients with
      skull base tumor were operated through transmaxillary approach, including 6
      patients with nasopharyngeal carcinoma, 5 with nasopharyngeal angiofibroma, 5
      with nasopharyngeal cystadenocarcinoma, 2 with olfactory neuroblastoma, 2 with
      poorly differentiated carcinoma, 2 with sarcoma, 1 with maxillary carcinoma, 2
      with schwannoma, and 2 with chordoma. Most of them (18/27) were recurrent tumor
      and 17/27 tumors involved important intracranial structures. All patients were
      followed up 2 - 33 months (average 16 months) and the clinical data was reviewed.
      RESULTS: The tumors could be totally removed in all patients. There were no
      operative mortality and morbidity. After operation, 2 patients died of cancer
      recurrence in 5 and 8 months separately. One patient had metastasis to the lungs
      11 months after operation. Two patients had local recurrence in 7 and 12 months
      postoperation seperately and live with the tumor now. The rest patients are back
      to their routine life. CONCLUSIONS: Transmaxillary approach facilitates the
      surgical removal of invasive skull base tumors. The exposure is wide. The lesion
      as well as the important anatomy structures can be viewed directly and clearly.
      The tumor removal could be done more thoroughly and safely. This approach is
      suitable for the patients in whom tumor involves the skull base extensively and
      may be difficult to deal with by other approaches.

PMID- 11955388
TI  - [Levels and clinical significance of CD44 (intron 9) and CD44v6 in malignant
      cerebroma].
AB  - OBJECTIVE: To investigate the expression of CD44 (intron 9) and CD44v6 in brain
      neoplasm. METHODS: CD44 (intron 9) and CD44v6 were detected in malignant
      meningoma, encephalic glioma, and normal encephalic tissues around the brain
      noeplasm respectively by using RT-PCR. RESULTS: The positive expression rate of
      CD44v6 was 92.86% (26/28) in malignant meningoma and 88.0% (22/25) in encephalic
      glioma. They were significantly higher than 5.0% (1/20) in normal encephalic
      tissues (P < 0.01). Mass values of malignant meningoma and encephalic glioma were
      higher than that of normal encephalic tissues (P < 0.01). The expression of CD44
      (intron 9) was higher in malignant meningoma and encephalic glioma than in normal
      encephalic tissues (P < 0.01). CONCLUSIONS: Detection of CD44 (intron 9) and
      CD44v6 might be helpful to the diagnosis of malignant cerebroma.

PMID- 11955387
TI  - [Telomerase activity and regulation in human neuroepithelial tumors].
AB  - OBJECTIVE: To investigate telomerase activity and expression of hTR and hTERT in
      human neuroepithelial tumors for exploring new strategy for clinical diagnosis
      and treatment. METHODS: Telomerase activity was detected by modified TRAP method
      and the expression of hTR and hTERT was measured by RT-PCR method in 65 human
      neuroepithelial tumors, respectively. RESULTS: The positive rates of telomerase
      and hTERT were 61.54% and 70.77% respectively in human neuroepithelial tumors,
      and the positive rate and their level of expression were correlated with the
      degree of malignancy of tumors positively. CONCLUSIONS: Telomerase activity and
      hTERT are significantly correlated with the degree of malignancyin human
      neuroepithelial tumors. hTERT may play a key role in the regulation of telomerase
      activity.

PMID- 11955389
TI  - [Changes of immune function in liver cirrhosis patients after splenectomy
      combined with resection of hepatocellular carcinoma].
AB  - OBJECTIVE: To study the changes of immune function in liver cirrhosis patients
      after splenectomy combined with resection of hepatocellular carcinoma (HCC).
      METHODS: Sixteen patients with HCC associated with liver cirrhosis were divided
      into two groups: splenectomy combined with hepatectomy (n = 7) and hepatectomy (n
      = 9). T-lymphocyte subsets such as CD4, CD8, CD4/CD8 and Th-lymphocyte cytokines
      such as IFN-gamma, IL2, IL10 in 7 ml peripheral venous blood before operation and
      two months after operation were examined and compared between the two groups.
      RESULTS: There was no significant difference in pre-operative CD4, CD4/CD8, IL2,
      IFN-gamma, IL10 levels in the two group. Two months after operation, the levels
      of CD4 (38.2% +/- 3.7%), CD4/CD8 (1.7 +/- 0.3), IFN-gamma [(104.4 +/- 14.9)
      pg/ml], IL2 [(98.6 +/- 18.6) pg/ml] were increased and those of CD8 (23.7 +/-
      13.7) pg/ml and IL10 [(55.5 +/- 11.2) pn/ml] were decreased in the two groups,
      but the changes in the group of splenectomy combined with hepatectomy were more
      obvious than those in the hepatectomy group. The levels of CD4 (32.5% +/- 4.0%),
      CD4/CD8 (1.1 +/- 0.1), IFN-gamma [(70.5 +/- 12.6) pg/ml], IL2 [(80.9 +/- 13.5)
      pg/ml] in the group of splenectomy combined with hepatectomy, were much higher
      than those in the hepatectomy group; those of CD8 (29.4% +/- 4.0%), IL10 [(89.4
      +/- 10.0) pg/ml] level were significantly lower than those in the hepatectomy (P
      < 0.05). CONCLUSION: Splenectomy combined with hepatectomy for HCC associated
      with liver cirrhosis donor decrease but promote the recover T-lymphocyte subsets
      and Th1/Th2 cytokines from imbalance and improve the patient's antitumor immune
      function.

PMID- 11955390
TI  - [Management of enteric fistula].
AB  - OBJECTIVES: To evaluate the essentials for successful management of entero
      cutaneous fistulas and their. METHODS: We analyzed. The therapeutic results of 1
      168 cases treated in a single center from January. 1971 to December. 2000.
      RESULTS: In these patients, the cure rate of fistulas was 93% and 37.1% after non
      operative treatment. Most cases died of sepsis (60/65 cases, 93.2%) with a total
      mortality of 5.5%. In 659 cases who had undergone operation for enteric fistula,
      647 (98.2%) recovered. The cure rate, mortality rate and successful rate of
      operation (94.2%, 4.4%, 99.7%) in the period of January. 1985 - December. 2000
      were better than those (90.4%, 8.2%, 95, 5%) in the early period of January 1971
      December 1984 (P < 0.05). CONCLUSIONS: The change of therapeutic strategy,
      improved technique in control of sepsis, rational nutritional support and careful
      monitoring of vital organs are essential to the management of enteric fistulas.
      How to increase the spontaneous closure of fistula, the therapeutic rate of
      specific enteric fistula (e.g. IBD, radiation enteritis) and the operative rate
      of enteric fistula in the early period requires further study.

PMID- 11955391
TI  - [Gene expression significance of beta-catenin, p53 and PCNA in PJS polyposis].
AB  - OBJECTIVE: To study the significance of beta -catenin, p53 and PCNA in PJS
      harmatoma. METHOD: Paraffin sections of 29 hamartomas of 18 patient with Peutz
      Jeghers syndrome, 19 patients with colorectal mucosa and 10 persons with normal
      mucosa were examined using LSAB. Positive cells were detected under light
      microscope. RESULTS: All 10 persons with normal mucosa showed p53 negative and
      beta - catenin positive. The beta - catenin protein was predominantly localized
      to the plasma membrane. PCNA index (PI) in normal mucosa was 10.56 +/- 7.51. The
      PI of hamartoma and cancer was 44.57 +/- 21.15 and 32.96 +/- 18.88. The PI of the
      two groups was significantly higher than that of the normal group. In hamartoma,
      the positive cells were mainly located in the low 1/3 part of the mucous glands.
      The positive rate of p53 was 24.1% (7/29) in hamartomatouspolyps and 57.9%
      (11/19) in colorectal carcinoma (chi(2) = 5.581, P < 0.05). Abnormal expression
      rate of beta- catenin in colorectal carcinoma was 73.7% (14/19) and 41.3% (12/29)
      in hamartomatous polyps. Some epithelial cells showed nuclear localization of
      beta- catenin and concentration of cytoplasm. (chi(2) = 4.825, P < 0.05).
      CONCLUSIONS: The proliferation activity of hamartomatous polyps increased
      significantly by multifactory interaction. p53 and beta- catenin play a role in
      the early stage of hamartoma- adenoma-carcinoma sequence but have a different
      mechanism in inducing colorectal cancer.

PMID- 11955393
TI  - [Single instillation of epirubicin for the prophylaxis of recurrent primary
      superficial bladder carcinoma].
AB  - OBJECTIVE: To determine the feasibility of single dose intravesical epirubicin in
      the prevention of recurrent superficial bladder carcinoma. METHODS: We compared
      the effect of intravesical epirubicin or mitomycin C on tumor recurrence and
      disease free interval and their side effects after treatment of superficial
      bladder tumor. 47 postoperative patients with stages Ta to T1 primary superficial
      bladder carcinoma of grades 1 or 2 were randomized into groups A: single 80 mg
      epirubicin; B: 40 mg consecutive epirubicin; C: 40 mg consecutive mitomycin C.
      Patients were followed up for clinical, analytical, and cystoscopic evaluations
      every 3 months. RESULTS: The disease free intervals of the three groups were
      found no significant differences (F = 3.25, P > 0.05). The recurrence rate was
      6.25% (1/16), 13.3% (2/15), 12.5% (2/16) (chi(2) = 0.496, P > 0.05) in groups A,
      B, and C at 1 year, and 33.3% (5/15), 26.7% (4/15), 25% (4/16) (chi(2) = 0.290, P
      > 0.05) at 3 years after operation, respectively. Side effects of group A (13.3%)
      were lower than those of group B (46.7%) or C (43.8%) (chi(2) = 14.56, P < 0.01).
      CONCLUSIONS: Single dose of epirubicin given intravesically immediately after
      tumor resection is effective in preventing tumor recurrence.

PMID- 11955392
TI  - [Severely burned patients after surgery: recombinant human growth hormone therapy
      its metabolic effects].
AB  - OBJECTIVES: To observe the effect of recombinant human growth hormone on
      metabolism in severely burned patients. METHODS: From January 1999 to January
      2001, 50 patients, aged 12 to 50 years, with over 30% total body surface area
      (TBSA) and 10% full-thickness burns, were randomized in a double-blind study. In
      the control group normal saline was used as a placebo (control group), while 0.3
      IU/kg(-1) /d(-1) recombinant human growth hormone was given from postoperative
      day 1 to day 10 in the rhGH group. The excised burn wounds were closed with
      microautograft and allograft skin. Blood samples were collected at 6:00 am for
      assaying of growth hormone, blood glucose, blood insulin, anti-insulin antibody,
      glucagon, cortisol, serum amino acid profile, transferring, proalbumin, total
      protein, dielectric, and resting energy expenditure (REE) was also measured.
      RESULTS: The concentration of blood GH in both groups was lower (t = 2.806, P <
      0.05) than that of physiological values before surgery. However, the
      concentration of GH on POD 3 in the rhGH group was significantly higher than that
      of normal values, but a higher level was observed on POD 7 in the rhGH group than
      that of the control group (t = 3.142, P < 0.05). Although the concentration of
      anti-insulin antibody was slightly increased, there was no significant difference
      between the two groups. The concentration of glucagons tended to decrease with an
      increase in the concentration of blood glucose, and it was marked in the rhGH
      group. There was no significant difference between the two groups. The
      concentration of cortisol was higher than normal values, but no significant
      difference was observed between the two groups. With the administration of rhGH,
      the plasma concentration of amino acids was lower than that of the control group
      (t = 2.714, P < 0.05), and the urinary output of 3-MH in the rhGH group was lower
      than that of the control group (t = 2.207, P < 0.05). CONCLUSIONS: Administration
      of rhGH in patients with major burn after surgery could improve their metabolic
      status, namely, increased lipolysis energy, accelerated protein synthesis,
      accelerated gluconeogenesis, reduced muscle proteolytic rate, and reduced REE
      expenditure. There is no effect on stress hormone. rhGH exerts a beneficial
      effect on metabolism in severely burned patients, but hyperglycemia is apt to
      occur, and water, Na(+), Cl(-) retention are suggested.

PMID- 11955394
TI  - [Recent outcome of bladder augmentation using deepithelialiezed segment of small
      intestine lined with urothelium].
AB  - OBJECTIVE: To evaluate urodynamically and clinically bladder augmentation using
      double-deepithelialized segment of the small intestine lined with urothelium to
      analyse the recent outcome to treatment of hyperreflexia neurogenical bladder.
      METHODS: 25 patients with neurogenical bladder underwent bladder augmentation
      using deepithelialized segment of the small intestine lined with urothelium (4 -
      14 years old, 16 males and 9 females) from October 1998 to October 2000. 21
      patients were followed up. Voiding cystoureterography and urodynamic and clinical
      evaluation were performed, and serum electrolyte, urea nitrogen and creatinine
      were tested before and 6 months to 2 years after operation. RESULTS: After
      operation, bladder volume, maximum urine flow rate and compliance were increased,
      but residual urine/bladder volume and detrusor pressure decreased. Uninhibitory
      contraction decreased in 15 patients. In 12 patients associated vesicoureteral
      reflux, clinical evaluation revealed poor outcomes before operation, but
      excellent (4 patients), good (9), effective (4), poor outcomes (4) after
      operation. Seven patients had urinary sensation recovered. Vesicoureteral reflux
      decreased in 9 patients. There were no electrolyte unbalance and abnormal renal
      function in all patients. CONCLUSIONS: Bladder augmentation using double
      deepithelialized segment of the small intestine lined with urothelium shows a
      better result currently.

PMID- 11955395
TI  - [Using unstable fractures of the distal end of the radius: open reduction and
      internal fixation with T - type plate].
AB  - OBJECTIVE: To treat unstable fractures of the distal end of the radius with open
      reduction and internal fixation with T-type plate. METHODS: 45 patients were
      treated with T-type plate. Bone graft was used in fifteen patients with severe
      bone defect. Clinical findings of 45 patients with fractures of the distal end of
      the radius (one is bilateral fractures) showed fairly good results. RESULTS: The
      patients were followed up for an average period of 25.36 months. 41 patients
      showed excellent or good results with a rate of 91.11%. CONCLUSION: It is
      difficult to reduce unstable fracture of the distal end of the radius in the way
      of close reduction. Re-displacement is frequent for external fixation and is not
      reliable in maintaining reduction. These fractures should be treated with early
      open reduction and internal fixation, and reasonable exercise should be taken
      after the operation. Good results can be predicted. The most important factors
      affecting final outcome include radial shortening and reduction of articular
      surface.

PMID- 11955396
TI  - [Diagnosis and treatment of cervical disc calcification in children].
AB  - OBJECTIVES: To investigate the diagnosis and treatment cervical disc
      calcification in children. METHODS: 13 children with cervical disc calcification
      were analysed retrospectively. Cervical pain was observed after influenza in 5
      children, suddenly cervical pain in 3, sudden wryneck in 3 cases. Two children
      with this disease were accidentally found after injury. RESULTS: 14
      calcifications of cervical disks were found in 13 children. Clinical symptoms
      disappeared after symptomatic management. Calcification disappeared in 5 months.
      CONCLUSIONS: Cervical disc calcification in children is a kind of benign self
      limited disease. Correst understanding of pathophysiologic course of this disease
      helps to avoid unnecessary surgery.

PMID- 11955397
TI  - [Circulation assist in the radical operation of retro-peritoneal malignancy with
      the inferior vena cava thrombotic involvement].
AB  - OBJECTIVE: To discuss the key role of various mode of circulation assist in the
      radical operation of retro-peritoneal malignancy with the inferior vena cava
      thrombotic involvement. METHODS: >From the June 1999 to the March 2001, 6
      patients with retro-peritoneal malignancy with thrombosis involving the inferior
      vena cava, were completely resected with various mode of circulation assist.
      RESULTS: All the patients operated have good outcomes and follow-up (1 - 20
      months) except one death 1 month after operation. CONCLUSION: According to the
      various types of tumor thrombi, individualized and technically feasible
      circulation assist mode should be utilized to achieve the satisfactory outcomes.

PMID- 11955398
TI  - [Microanatomy study on sinus triangle region].
AB  - OBJECTIVES: To explore shape and position relationship of the structures with in
      sinus triangle region, and provide the anatomic foundation for extended
      presigmoid operative approach. METHODS: Ten cadaveric heads and 15 skull-base
      specimens fixed with 10% formalin, with aid of operative microscope, the shape
      and relations of structures with in the sinus triangle region were observed and
      microphotographed. Four cadaveric heads were sectioned in different plane using
      collodion embedding process. RESULTS: Jugular blub (JB) had high -placed jugular
      blub (HJB), normal jugular blub (NJB) and low-placed jugular blub (LJB). The
      incidence of HJB was 8% and 18% for the left and right sides (P < 0.01). The JB
      dome can extend upward the hypotympanic cavity and the posterior wall of the
      internal acoustic meatus. The incidence of NJB and LJB was 36% and 30%, and 6%
      and 2% respectively. The level distance between the posterior semicircular canal
      and petrosal posterior surface was (4.1 +/- 1.1) mm. The distance between the JB
      and vertical part of the facial nerve was (3.2 +/- 0.5) mm and (2.0 +/- 0.4) mm.
      The distance between the JB and posterior margin of the internal acoustic port
      was (7.5 +/- 1.7) mm and (4.0 +/- 1.0) mm. CONCLUSIONS: Knowing the shape and
      position relationship of structures in the sinus triangle region is favorable for
      preserving the important structures in extended presigmoid operative approach.

PMID- 11955399
TI  - [The role of beta irradiation on neointimal formation and apoptosis in vein
      grafts model].
AB  - OBJECTIVE: To evaluate the effect of beta irradiation on intimal proliferation
      and apoptosis in vein grafts. METHODS: Autogenous vein graft model was
      established in 80 rats by transplanting the internal branch of the jugular vein
      to the carotid artery by end to end anastomosis. The veins were irradiated by
      (32)P solution before anastomosis. Two dose schedules were studied: control group
      (graft, nonirradiated) and radiation group (20 Gy). The grafted veins were
      harvested at 3, 1, 2 and 4 week respectively after the operation. intimal
      hyperplasia (IH), smooth muscle cell (SMC), proliferation, p53, bcl-2 and bax
      were observed pathologically and immunohistochemically. They were analyzed by a
      computerized system. The presence of apoptotic VSMC was demonstrated by TUNEL
      method. RESULT: There was a significant decrease in the average intimal thickness
      at 7, 14 and 28 days (t = 15.694, P < 0.05) in the radiation group.
      Immunohistochemical analysis of PCNA indicated decreased positive cells in the
      radiation group compared with the controls at 1 and 2 weeks (t = 60.157, P <
      0.01). Apoptosis of VSMC was higher in the radiation group than in the control
      group at 2 weeks (t = 56.176, P < 0.01). There was no significant difference in
      expression of P(53) between the two groups, and there was a significant increase
      in bax/bcl-2 in the radiation group at 2 weeks (t = 9.783, P < 0.05). CONCLUSION:
      These preliminary results demonstrated that low dose of beta irradiation in the
      vein graft inhibits SMC proliferation and induces the apoptosis of VSMC in rats.

PMID- 11955400
TI  - [X-ray combined with cytosine deaminase suicide gene therapy enhances killing of
      colorectal carcinoma cells in vitro].
AB  - OBJECTIVE: To study the effect of X-ray on gene transfer and the antitumoral
      effect of X-ray combined with suicide gene therapy on colorectal carcinoma cells.
      METHODS: Green fluorescent protein (GFP) was seen under fluorescent microscope.
      GFP gene was used for reporting gene to learn gene transfer efficiency and gene
      expressing time under the influence of radiation. G418 was used to select
      cytosine deaminase (CD) positive neoplasm cells and CD gene transfer efficiency
      was tested by cloning efficiency. Antitumoral effect of X-ray combined with CD
      and 5-FC on colorectal carcinoma cells was tested by MTT. RESULTS: 4 Gy radiation
      could improve supercoiled plasmid DNA transfer efficiency for about 2 - 4 times
      and 30 times for linearized plasmid DNA. The mean durations of GFP gene
      expression treated with 4 Gy radiation were 14 d for supercoiled plasmid and 21
      and for linearized plasmid, while in control group, the time was 12 d. Middle
      dose radiation combined with CD and 5-FC could kill 99 percent of colorectal
      carcinoma cells, while in the control group, 5-FC only killed 15 percent of
      colorectal carcinoma cells which were transduced with CD gene. CONCLUSIONS: X-Ray
      combined with suicide gene therapy may be used as a promising method for treating
      colorectal neoplasm.

PMID- 11955401
TI  - [SYTO/EB dyes for detection of skin viability].
AB  - OBJECTIVE: the main purpose of this study is to develop an assay for detection of
      skin viability in situ. METHODS: Two nucleic acid dyes, SYTO 13 and ethidium
      bromide (EB), are used to assess the viability of skin tissue. The viability of
      cells can be determined by different colors under fluorescence microscope. In
      this study, the recovery of skin restored at 4 degrees C for different periods is
      measured by SYTO/EB dyes and a type of indirect assessment, WST-1. Then both
      results are compared. RESULTS: The results measured by two methods showed that
      the viability of skin tissue was nearly 30% after two weeks storage. At any point
      of experiment, the data from two methods have not obvious variance. CONCLUSION:
      The assessment of skin viability by SYTO/EB is also quick, sensitive and
      convenient. At the same time the viability of any type of cells can be observed
      in situ. So it can be considered as an available method for detection of skin
      viability.

PMID- 11955403
TI  - [Role of interferon alpha in the management of severe acute pancreatitis].
AB  - OBJECTIVE: To investigate the efficacy of IFN-alpha on severe acute pancreatitis
      (SAP) of IFN-alpha. METHODS: A SAP model was developed in adult male rats by
      retrograde injection of 5% sodium taurocholate in the pancreatic duct. Serum
      amylase was measured by the blue-starch method and serum cytokines were
      determined by ELISA. RESULTS: Compared with to the control group, less pancreatic
      injury and lower amylase level were observed treat in the rats with IFN-alpha. In
      contrast, the concentration of IL-10 was higher. CONCLUSION: IFN-alpha has
      significant curative effect on SAP.

PMID- 11955402
TI  - [Expression of ET-1 mRNA in the lung of hepatopulmonary syndrome rats].
AB  - OBJECTIVE: To investigate the expression of ET-1 mRNA in the lung of rats with
      hepatopulmonary syndrome. METHODS: Male Sprague-Dawley rats were divided into
      four groups: SO, IHPH, PHPH and PCS. Two weeks after production of rat models,
      all measurements were performed. Arterial blood gas was analyzed. The
      concentrations of NO and ET-1 in lungs were measured by using radioimmunoassay.
      In situ hybridization, ET-1 mRNA expressions were detected in lung tissue
      sections with digoxin-labeled ET-1 oligonucleotide probes. Liver and lung tissues
      and all the results of in situ hybridization were analyzed by one pathologist. At
      a magnification of 10 x 40, percent areas of positive stains were detected to
      indicate the expressions of ET-1 mRNA in the arteries, capillaries and branches.
      RESULTS: Arterial blood gas analysis showed that PaO(2) (mmHg) decreased more
      significantly in IHPH (73.85 +/- 6.51) rats than in PHPH (97.39 +/- 1.33), PCS
      (95.23 +/- 2.22) and SO rats (99.05 +/- 0.75). Alveolar-arterial oxygen gradient
      (A-aG) (mmHg) increased more significantly in IHPH rats (32.99 +/- 6.57) than in
      PHPH (4.98 +/- 1.69), PCS (6.51 +/- 2.04) and SO rats (3.23 +/- 0.81). Changes of
      vascular active substance in plasma and lung indicated that the level of lung NO
      of IHPH (19.78 +/- 5.33) was increased significantly more than that of PHPH
      (13.21 +/- 3.99) and PCS (13.89 +/- 3.16). These levels in lung homogenate
      increased more significantly than those SO (8.71 +/- 1.68). The levels of ET-1 in
      IHPH rats (195.1 +/- 36.2) was significantly lower than in PHPH (234.8 +/- 71.0),
      PCS (240.4 +/- 66.5) and SO rats (271.8 +/- 40.6). ET-1 mRNA in situ
      hybridization showed that there was no significant difference in positive
      expression of ET-1 mRNA in alveolar arteries and small bronchi. The expression of
      ET-1 mRNA was significantly lower in alveolar capillary endothelia (5.12 +/-
      1.27) than in PHPH (7.43 +/- 0.83), PCS (7.07 +/- 0.86) and SO (7.81 +/- 1.98)
      rats. CONCLUSION: The low expressions of ET-1 mRNA in HPS rat alveolar capillary
      endothelia accompanied by decreased ET-1 levels in lung may play an important
      role in the mechanism of HPS.

PMID- 11955405
TI  - [Detection of sentinel lymph node in patients with breast cancer].
AB  - OBJECTIVE: To evaluate the technique and significance of the sentinel lymph node
      (SLN) biopsy using different methods in patients with breast cancer. METHODS:
      Seventy-one female patients with node-negative breast cancer diagnosed by fine
      needle biopsy or frozen section underwent lymphatic mapping. They were divided
      into 4 groups: methylene blue, isosulfan blue, (99m)technetium-labelled sulfur
      colloid, combined vital blue dye and radiocolloid. The number of each group was
      24, 29, 8 and 10 respectively. The SLN was identified and removed, followed by a
      definitive cancer operation, including a complete axillary node dissection.
      Pathological examination of the SLN was made with HE and immunohistochemical
      staining. Pathologic characteristics of SLN and other axillary nodes were
      analyzed. RESULTS: Among the 71 patients, 60 were (84.5%) confirmed by SLN
      biopsy. The positive rates were 75.0% (18/24) for methylene blue group and 86.2%
      (25/29) for isosulfan blue group, respectively. Seven positive cases were
      detected by (99m)technetium-labelled sulfur colloid and all the positive cases by
      combined vital blue dye and radiocolloid. The total sensitivity was 83.3% and the
      sensitivity for each group was 70.0%, 90.0%, 100% and 100%, respectively. The
      total false negative rate was 16.7% and the false negative rate for each group
      was 30.0%, 10.0%, 0 and 0, respectively. The total accuracy rate was 93.3% and
      the accuracy rate for each group was 83.3%, 96.0%, 100% and 100%, respectively.
      The time of finding the SLN was 29, 22, 7, 6 min respectively. CONCLUSIONS: SLN
      biopsy is technically possible in patients with breast cancer. Most of SLNs can
      probably reflect the histological characteristics of the axillary lymph nodes.
      Combination of vital blue dye and isotope makes mapping exact and satisfactory
      and it may be the best choice among the four methods.

PMID- 11955404
TI  - [Treatment of organ transplant rejection with low doses of CsA and CTLA4-Ig].
AB  - OBJECTIVE: To study on treating organ transplant rejection with low doses of CsA
      and CTLA4-Ig. METHODS: We set up a rat's cardiac transplant rejection model by
      Ono's way. The experimental rats were divided into four groups: group A: without
      any treatment; group B: intraperitoneal injection of CsA at 10 mg / (-1) / (-1) 1
      - 7 days; after operation group C: intraperitoneal injection of 100 microgram
      CTLA4-Ig after 2nd operative day; group D: intraperitoneal injection of CsA 2 mg
      / (-1) / (-1) 1- 7 days after operation. 50 microgram CTLA4-Ig was given
      intraperitoneally on the 2nd day postoperation. The survival days of allograft,
      serum concentration of IL-2, and histological changes were tested. RESULTS: The
      allograft survival time of the four groups was 7.2 +/- 0.7 (group A), 19.4 +/-
      2.07 (group B), 31.6 +/- 1.8 (group C) and 24.6 +/- 2.07 (group D) respectively.
      There were significantly differences among the groups (P < 0.05). The survival
      time in group D was more prolonged than that in group B (P < 0.05). The
      concentration of IL-2 was significantly decreased after operation. Significant
      difference was observed between the control group and each treated group (P <
      0.01). In group A, B, C and D allograft rejection was graded IV, II, I and I
      respectively. CONCLUSION: CTLA4-Ig had a stronger immunosuppression than did CsA.
      The low doses of CsA and CTLA4-Ig had show a synergistic immunosuppression in
      allograft transplantation.

PMID- 11955406
TI  - [Expression of human mammaglobin mRNA in peripheral blood of breast cancer and
      their implication].
AB  - OBJECTIVE: To study the expression of human mammaglobin (hMAM) mRNA in the
      peripheral blood of breast cancer patients and its implication. METHODS: The
      expression of human mammaglobin mRNA was determined by using RT-PCR method in 56
      patients with peripheral blood breast cancer, 8 patients with breast hyperplasia
      and 8 women with normal breast. The expression of hMAM mRNA was compared with
      biological significance and change of hMAM mRNA in chemotherapy after operation.
      RESULTS: The expression of hMAM mRNA was negative in 8 patients with breast
      hyperplasia, 8 women with normal breast and 56 patients with breast cancer, The
      positive rate was 30.4% (17/56) (chi(2) = 19.766, P < 0.01). The expression of
      hMAM mRNA in peripheral blood was not correlated with clinical stage, primary
      tumor size and patients age (chi(2) = 1.256, P > 0.05). After short-term large
      dose of chemotherapy, 41.2% (7/17) patients turned positive before operation to
      negative hMAM mRNA expression and negetive expression before operation positive
      expression after chemotherapy. CONCLUSIONS: This study suggests that hMAM is
      sensitive and specific for breast cancer. Detection of the expression of hMAM
      mRNA in peripheral blood of breast cancer is of value in the diagnosis and
      judgement of prognosis of breast cancer.

PMID- 11955408
TI  - [Effect of different estrogen receptor subtypes on vascular endothelial growth
      factor protein expression in human breast cancer samples].
AB  - OBJECTIVES: To evaluate the relationship of vascular endothelial growth factor
      expression with estrogen receptor (ER) subtypes in fresh human breast cancer
      samples, and study the potential effect of ER subtypes on tumor angiogenesis.
      METHODS: Western blot was used to detect the VEGF and ERbeta protein expression
      in 86 fresh samples of human breast cancer. ERalpha was analyzed by
      immunohistochemistry routinely. RESULTS: Among 86 samples, 42 (48.8%) showed low
      expressed VEGF and 44 (51.2%) high expressed VEGF. The level of VEGF protein was
      correlated with ERbeta. In high expressed VEGF group, ERbeta was also highly
      expressed (chi(2) = 7.36, P < 0.01). But there was no significant difference
      between VEGF protein level and ERalpha (P > 0.05). CONCLUSION: In human breast
      cancer samples, VEGF may be related to ERbeta protein expression.

PMID- 11955407
TI  - [Significance of MEK-ERK cascade in the development of human breast carcinoma].
AB  - OBJECTIVE: To investigate the MEK and ERK expression and their relationship with
      clinicopathological parameters in human breast carcinoma, and the effect of
      preoperative chemotherapy on MEK and ERK protein expression. METHODS: Samples
      were obtained from 56 patients with breast carcinoma and 8 patients with benign
      tumors. Sixteen of the 56 patients received preoperative chemotherapy. Western
      blot and immunohistochemistry were used to measure the expression of MEK1, MEK2
      and ERK1, ERK2 protein. RESULTS: MEK2 and ERK1, ERK2 protein levels were
      increased in breast carcinoma tissue compared with those in adjacent normal
      tissues (t = 7.244, 5.959, 3.735, P < 0.01) and benign tumors (t = 2.206, P <
      0.05). The levels of MEK1 were decreased. The expression of MEK2 protein in ER
      negative patients was higher than that in ER positive ones. MEK2 protein levels
      were lower in patients who received preoperative chemotherapy than in those who
      did not. CONCLUSION: Overexpression of MEK-ERK may play an important role in the
      development of human breast carcinoma. MEK and ERK protein expressions are
      inhibited by preoperative chemotherapy.

PMID- 11955409
TI  - [Angiogenesis and the expression of nm23-H(1) tumor metastatic suppressor gene in
      primary breast carcinoma and their relations to lymph node metastasis].
AB  - OBJECTIVE: To study angiogenesis and the expression of nm23-H(1) tumor metastatic
      suppressor gene in primary breast carcinoma and their relationship with axillary
      lymph node metastasis. METHODS: Intratumoral vascularization in 80 cases of
      breast cancer was observed preoperatively by power doppler imaging (PDI) and
      analysed with computer-assisted quantative assessment, and the expression of
      microvessel density (MVD) and nm23 protein was determined by immunohistochemical
      technique. RESULTS: Blood flow signals and blood vessels postitive area within
      masses were more in axillary node positive (LN+) group than in axillary node
      negative (LN-) group (t = 7.07, P < 0.01), MVD expression were higher in the LN+
      group than in the LN- group (t = 6.34, P < 0.01). Meanwhile the expression of
      nm23-H(1) protein was lower in the LN+ group than in the LN- group, and
      significant correlation was found between angiogenesis and the expression of nm23
      H(1) protein. CONCLUSIONS: Angiogenesis and the expression of nm23-H(1) protein
      may play an important role in the lymphatic metastasis process of breast cancer.
      Furthermore, angiogenesis may correlates with the expression of nm23-H(1) protein
      in that progress.

PMID- 11955410
TI  - [Clinical and histological factors associated with sentinel node identification
      in breast cancer].
AB  - OBJECTIVE: To study the predictive factors that are associated with
      intraoperative identification of the sentinel lymph node (SLN). METHODS:
      Lymphatic mapping using blue dye was performed in 108 patients with stage I and
      II operable primary breast cancer. Subsequently the patients received operations
      of breast cancer including axillary dissection. Clinical and histological factors
      were assessed to determine those that were associated with intraoperative
      identification of the SLN. RESULTS: The sentinel node was identified at the time
      of surgery in 84 patients (77.78%). Of the clinical factors assessed, age(y) < 50
      (chi(2) = 7.447, P < 0.01), tumour in the upper quadrant (chi(2) = 6.330, P <
      0.05), diagnosis by preoperative biopsy (chi(2) = 5.509, P < 0.05), successful
      mapping of the lymphatic duct (chi(2) = 13.125, P < 0.01) were significant in
      identifying the sentinel node at operation. No histological factor was associated
      with intraoperative identification of the sentinel node. CONCLUSION: There are
      the possibility of failure of SLN identification at sentinel lymph node biopsy.
      Our results suggest that the best predictor of intraoperative sentinel node
      identification is the visualization of the lymphatic duct on mapping by blue dye.
      Other factors such as age, tumour site as well as diagnostic method are also
      important in determining the success of the procedure.

PMID- 11955411
TI  - [Microsurgical management of tethered cord syndrome].
AB  - OBJECTIVE: To assess the results of 26 patients with tethered cord syndrome (TCS)
      after microsurgical operation. METHODS: Twenty-six patients with TCS were treated
      microsurgically and their clinical data were analyzed retrospectively. RESULTS:
      72% of the patients with TCS showed significant improvement. Surgical outcome was
      excellent in relieving pain and sensorimotor deficits, but bladder dysfunction.
      CONCLUSION: Early diagnosis and adequate surgical release are the keys to a
      successful outcome.

PMID- 11955412
TI  - [Application of neuroendoscopy in brain surgery].
AB  - OBJECTIVE: To investigate the effect of neuroendoscope on surgery. METHODS: 315
      patients were treated with neuroendoscope. Endoscopic neurosurgery (EN) was used
      in 219 patients, endoscope-assisted microneurosurgery (EAM) in 72, and endoscope
      controlled microneurosurgery (ECM) in 24. RESULTS: 201 (91.8%) of the 219
      patients underwent EN effectively. In 72 patients who underwent EAM there was
      less retraction during tumor removal and visual control was improved. 21 (87.5%)
      of the 24 patients underwent ECM effectively. No severe complications were
      observed. CONCLUSION: Neuroendoscopy can reduce tissue trauma, improve
      visualization during tumor removal, and reduce complications.

PMID- 11955413
TI  - [Spinal dural arteriovenous fistulae associated with perimedullary arteriovenous
      fistulae: imaging characteristics and surgical treatment].
AB  - OBJECTIVE: To enhance the clinical doctors' cognizance of atypical spinal dural
      arteriovenous fistulae (SDAVFs) associated with perimedullary anteriovenous
      fistulae (PMAVFs). METHODS: The clinical imaging and surgical therapy of 3
      patients with PMAVFs were analyzed retrospectively. RESULTS: The clinical
      presentations of the 3 patients were not significantly different from those of
      typical SDAVFs. They were verified by repeated spinal angiography that the
      anterior spinal artery (ASA) is supplied to the drainage-vein. The 3 patients
      were treated surgically. First two operations were performed to eliminate the
      supply of ASA and dural branch, then the supply of the dural branch was
      amputated, and finally both the ASA and dural branch supplies were excised
      successfully. Clinical symptoms of the 3 patients were improved after treatment.
      CONCLUSIONS: It is necessary to perform thorough spinal angiography in patients
      with SDAVFs to exclude another fistula. The key point in the treatment of such
      patients is successfully to terminate both the spinal feeder and dural branch
      feeder.

PMID- 11955414
TI  - [Late-stage emphysema treated with lung volume reduction: report of 22 cases].
AB  - OBJECTIVE: To Summarize the clinical experience in the treatment of late-stage
      emphysema by lung volume reduction (LVR) in 5 years. METHODS: We retrospectively
      studied the indications, contraindications, operation procedures and
      complications of LVR in 22 patients. RESULTS: Before operation, the average
      FEV(1) was 24.5%, RV 196.8%, and TLC 130.5%; after operation they were 27.8%,
      148.8% and 112.5%, respectively. 16 patients needed inhaling oxygen before
      operation, and 5 after operation. 16 patients finished 6-minute walking test with
      an average of 198 m, all patients walked much longer with an average of 256 m
      after operation. 3-degree lung function was observed in 14 patients, and 4-degree
      before operation in 8 patients; but 2-degree lung function in 5 patients, 3
      degree in 13, and 4-degree in 4 after operation. CONCLUSIONS: Heterogeneous type
      emphysema with clear target area, especially bullous emphysema is the best
      indication for LVR. Lung function and life quality could be much improved
      postoperatively. Homogeneous type could also be treated with LVR in highly
      selected cases. TLCO < 20% is not an absolute contraindication, others standards
      need further investigation. Video-assistant thoracoscopic surgery (VATS) with
      subaxillary small incision for LVR is safe, reliable and effective. Application
      of stapler buttressing with bovine pericardia could decrease air leakage
      postoperatively.

PMID- 11955415
TI  - [Clinical analysis of the children with multiple ventricular septal defects].
AB  - OBJECTIVE: To review the experiences in surgical management and diagnosis for the
      children with multiple ventricular septal defects (VSDs). METHODS: The clinical
      data of 21 children with multiple VSDs (8 males, 13 females) were analysed
      retrospectively. Multiple muscle defects in all patients were repaired by left
      ventricle incision and their near future clinical outcome was investigated.
      RESULTS: The accuracy of diagnosis was 95.2% and the mortality was 9.5%. No
      residual shunts were found. Complete atrioventricular block was found early in 2
      patients postoperation. CONCLUSIONS: The operative outcome of children with
      multiple VSDs is satisfied. For these patients detailed preoperative color flow
      mapping and careful observation during operation are essential to increase the
      accuracy of diagnosis and prevention of residual shunts.

PMID- 11955416
TI  - [Influences of portal pressure change on intestinal permeability in patients with
      portal hypertension].
AB  - OBJECTIVES: To investigate intestinal permeability in patients with portal
      hypertension and to search for a relationship with portal pressure. METHODS:
      Twenty patients with portal hypertension were divided two groups (A, B), 10
      patients per group. In group A patients were treated with combined TIPS and
      modified Sugiura. In group B, patients were treated with modified Sugiura only.
      Intestinal permeability was assessed before operation, two weeks after TIPS, and
      two weeks after modified Sugiura, and 20 healthy control subjects were also
      assessed. RESULTS: Intestinal permeability was significantly higher in patients
      with portal hypertension than in healthy controls (0.132 +/- 0.110 vs. 0.032 +/-
      0.018, P < 0.01). In group A, portal pressure and intestinal permeability
      decreased two weeks after TIPS (P < 0.05) and no obvious change was noted two
      weeks after modified Sugiura; but they were significantly lower than those before
      TIPS (P < 0.05). In group B intestinal permeability was not different before and
      after operation. Intestinal permeability in group A was not different from that
      in group B before treatment, but significantly lower after modified Sugiura (P <
      0.05). Portal pressure was significantly correlated with intestinal permeability
      (r = 0.627, P < 0.01). CONCLUSIONS: This study shows that combined TIPS and
      modified Sugiura can lower portal pressure and intestinal permeability, and
      enhance the therapeutic efficacy on portal hypertension.

PMID- 11955417
TI  - [Application of microsurgical technique to hepatic artery reconstruction in liver
      transplantation].
AB  - OBJECTIVE: To explore the value of the microsurgical technique in the
      reconstruction of hepatic artery. METHODS: From September 2000 to June 2001, we
      performed liver transplantation for 11 patients including living related liver
      transplantation (4) and 7 orthotopic liver transplantation (7). Arterial
      reconstruction was performed under an operating microscope. RESULTS: No patients
      developed hepatic arterial thrombosis and serious complication, nor death for
      multiple organ failure. CONCLUSION: Microsurgical technique in reconstruction of
      the hepatic artery can improve surgical outcome, not only in orthotopic liver
      transplantation but also in living related liver transplantation.

PMID- 11955419
TI  - [Ulnar-side wrist pain unduced by the compression of the dorsal branch of the
      ulnar nerve: anatomical and clinical study].
AB  - OBJECTIVES: To investigate anatomical mechanism of the ulnar wrist pain caused by
      the compression of the dorsal branch of the ulnar nerve, and discuss the
      diagnosis and treatment of the compression. METHODS: 40 sides of the upper
      extremities of adult cadavers were studied anatomically. The dorsal branch of the
      ulnar nerve and its relationship to the surroundings was dissected and observed
      grossly and microscopically. 13 cases of the compression of the dorsal branch of
      the ulnar nerve were treated and followed up. RESULTS: The dorsal branch of the
      ulnar nerve was penetrated from the deep of the flexor carpi ulnaris muscle 5.6
      approximately 6.8 cm proximally from the styloid process of the ulna, then ran
      along the ulna and divided into 2 approximately 3 big branches at the medial side
      of the head of the ulna. The transverse branch was apt to injury during wrist
      movement as it crossed or rounded the head of the ulna where it was close to the
      peristeam. Seven of 13 cases of the compression of the dorsal branch of the ulnar
      nerve were treated by local block, and 6 by surgical neurolysis. Nine cases of
      this group got showed good effect without recurrence after 4 months to 1 year
      follow-up. CONCLUSION: The anatomical basis of the compression of the dorsal
      branch of the ulnar nerve is repetitive traction to this nerve during wrist
      movement, and the compression of the transverse branch is the main cause of ulnar
      wrist pain. The compression of the dorsal branch of the ulnar nerve should be
      considered to the patients with ulnar wrist pain and abnormal sensation along the
      dorsal ulnar side of hand.

PMID- 11955418
TI  - [Primary lymphoma of the spleen: clinical analysis of 23 cases].
AB  - OBJECTIVE: To investigate the best diagnostic and therapeutic method for primary
      lymphoma of the spleen. METHODS: Clinicopathologic features of 23 patients
      treated from January 1956 to August 1999 were analyzed retrospectively. RESULTS:
      All patients but one for exploration only (96%) underwent resection of the tumor.
      They accepted chemotherapy after operation. 23 patients were confirmed
      pathologically. B-cell type non-Hodgkin's lymphoma was noted in 21 patients and T
      cell letion in 2. According to Ahman's staging, 9 patients belonged to stage I, 8
      stage II, and 6 stage III. The 5-year survival rates were 50%, 40% and 16%
      respectively. CONCLUSIONS: The diagnosis of splenic lymphoma is dependent mainly
      on B-ultrasound examination and CT scanning. Splenectomy combined with
      chemotherapy may provide optimum therapy for patients with splenic lymphoma.

PMID- 11955420
TI  - [Desmoplastic small round cell tumor: report of 2 cases].
AB  - OBJECTIVE: To recognize the characteristics of desmoplastic small round cell
      tumor (DSRCT) and improve the standard of diagnosis. METHODS: We retrospectively
      reviewed the clinical data on the treatment of 2 patients with DSRCT in terms of
      their conditions, tissue sources, pathologic characteristics, immunohistochemical
      methods, clinical manifestation, diagnosis, treatment and prognosis. RESULTS:
      Clinical manifestations were complicated. The 2 patients were mis diagnosed
      before operation. Their tumors consisted of irregular nests of small and round
      cells, with nuclear hyperchromatism and scant cytoplasm embedded in a plenty of
      fibrous connective tissues. The edge of the nest was clear, with different sizes
      and shapes. Immunohistochemically, the 2 patients were positive for CK or EMA,
      NSE, des and vim of the epithelium, nerve, muscle and interstitial. They died 9
      months after operation. CONCLUSIONS: The tumor may occur in the abdomen, pelvic
      cavity and other sites, with different clinical manifestations. Routine
      examination should be replaced by immunohistochemical test for correct diagnosis
      of the tumor. Prognosis of most patients is not good.

PMID- 11955421
TI  - [Spontaneous inflammatory diseases in ankylosing spondylitis transgenic mice].
AB  - OBJECTIVE: To confirm the role of HLA-B2704 and hbeta(2)m gene in the
      pathogenesis of spontaneous inflammatory diseases by establishing HLA-B2704 and
      hbeta(2)m double transgenic mice model of ankylosing spondylitis. It will provide
      a powerful animal model for exploring the etiology, prevention and treatment of
      B27-relevant diseases. METHODS: The screening, identification and expression of
      HLA-B2704 and hbeta(2)m gene were determined by PCR, dot blot, Southern blot
      hybridization, RT-PCR, flow cytometry and immunohistochemistry. HE staining was
      performed for the diseased mice. RESULTS: Eight double transgenic mice bearing
      high copy developed spontaneous dermatosis, arthritis and nail changes in the
      rear paw. The results of flow cytometry in normal mice, B27 single transgenic
      mice, and HLA-B27/hbeta(2)m double transgenic mice were 0.63%, 7.87% and 35.87%
      respectively. HLA-B2704 antigen was high expressed on the cell surface, but not
      evident on those of B27 single transgenic mice. CONCLUSIONS: HLA-B2704 heavy
      chain can induce spontaneous inflammatory diseases in the transgenic mice.
      Hbeta(2)m can form a stable complex with HLA-B27 and may stabilize and enhance
      the expression of HLA-B2704 on the cell surface.

PMID- 11955422
TI  - [The influence of escharectomy during shock stage on skeletal muscle proteolytic
      rate in severely scalded rats].
AB  - OBJECTIVES: To observe the changes in proteolytic rate and the influence of
      escharectomy and skin-grafting during shock stage on the proteolytic rate of
      skeletal muscle in severely scalded rats, and to investigate necessity of
      escharectomy during shock stage. METHODS: Wistar rats afflicted with 30%TBSA
      (total body surface area) full-thickness burn on the back were randomly divided
      into 3 groups: burn injury group (group B), escharectomy during shock stage group
      (group S), and escharectomy after shock stage group (group N). Escharectomy and
      skin-grafting was performed on the postburn day 1 (PBD1) and PBD4 in group S and
      N. The extensor digitorium longus (EDL) muscle was collected using a technique
      without injury to the muscle, and the proteolytic rate of the EDL was determined
      by the in-vitro muscle incubation system with sufficient oxygen supply and amino
      acid automatic analyzer. RESULTS: The total proteolytic rate (TPR) in rat EDL
      muscles increased significantly (t > 2.988, P < 0.01) on PBD1, but no prominent
      changes were observed at other time points. There were no statistically
      significant changes in TPR between group S and group N, but the myofibrillar
      proteolytic rate (MPR) in rat EDL muscles increased markedly at each time point
      after scald (t > 2.988, P < 0.01). The MPR in group S decreased significantly as
      compared with that in group N on PBD2, 4, 5 (t = 2.311, P < 0.05; t = 3.054,
      3.319, P < 0.01), and the mean values were 3.17, 2.33, 1.75 nmol/wet weight in
      g/3 h, respectively. No significant changes were observed between group N and S.
      CONCLUSION: The high protein catabolism of skeletal muscle can be alleviated by
      escharectomy and skin-grafting during shock stage, and it is beneficial to
      organics.

PMID- 11955423
TI  - [Protective effects of Zn-metallothionein on erythrocyte membrane of rats with
      severe scalding after delayed resuscitation].
AB  - OBJECTIVE: To study the antagonism of Zn-metallothionein (Zn-MT) to oxidative
      stress of rats with severe scalding after delayed resuscitation. METHODS: 27
      Wistar rats were randomly divided into three groups: normal control; burn with
      delayed fluid resuscitation group; and Zn-MT protected group. The rats were
      scalded with 30% total body surface area (TBSA) third degree burn. Four hours
      after injury, they were resuscitated, but Zn-MT (1 x 10(-5) mol/L) was given in
      the third group rats. 24 hours after they were scalded, blood was taken, RBCs
      were separated and labeled with electron spin resonance (ESR) spin label 3
      maleimido-proxy l to detect membrane protein conformation. The serum was
      collected and added into the reaction system of xanthine, xanthine oxidase and
      ESR spin trap 5, 5-dimethylpyroline-N-oxide to assay the levels of superoxide
      dismutase (SOD) by ESR. RESULTS: The ratios of strong solidity and weak solidity
      of RBC membrane proteins in the three groups were 0.352 +/- 0.043, 0.409 +/-
      0.027, and 0.386 +/- 0.062 respectively, and the revolved times of membrane
      proteins were 1.300 +/- 0.210, 1.576 +/- 0.190 and 1.381 +/- 0.210 seconds
      respectively. Compared to the first group, the membrane protein conformation in
      the second group was changed remarkably, and the speed of membrane protein
      movement decreased significantly. However, those changes were alleviated
      obviously by Zn-MT. The SOD levels in serum of the three groups rats were 73.2%
      +/- 1.4%, 48.8% +/- 3.8% and 66.8% +/- 3.2% respectively. Compared to the normal
      control group, the SOD levels in serum of the second group decreased obviously.
      However, an excess of oxygen free radicals produced after injury could be
      scavenged by Zn-MT. CONCLUSION: RBC membrane proteins of rats with severe
      scalding after delayed resuscitation were injured by oxygen free radicals
      produced after injury, and Zn-MT could alleviate this injury.

PMID- 11955424
TI  - [Experimental study of therapy effects of anti -VEGF antibody on osteosarcoma].
AB  - OBJECTIVE: To investigate the effect of anti-VEGF antibody on angiogenesis
      induced by osteosarcoma OS-732 cell line and tumor growth. METHODS: With a tumor
      model on the chick embryo chorioallantoic membrane (CAM), the inhibition of
      angiogenesis and tumor growth by anti-VEGF antibody were observed under a stero
      microscope and a light microscope. Furthermore, the proliferation and apoptosis
      in tumor cells and endothelial cells (EC) were studied by TdT-mediated duTP nick
      and labeling (TUNEL) and immunohistochemical staining using proliferating cell
      nuclear antigen (PCNA) monoclonal antibody. RESULTS: VEGF polyclonal antibody
      administration in tumor-bearing chick embryo resulted in growth arrest of
      xenografts and a markedly reduction in the new capillaries which converged upon
      the tumor. The tumor cell apoptotic index was higher in the anti-VEGF antibody
      treated group than the negative control group, but the proliferation index was
      not significantly different between them. At the same time, increased apoptosis
      and decreased proliferation in EC were also noted. CONCLUSION: VEGF polyclonal
      antibody is able to inhibit the angiogenesis induced by OS-732 obviously,
      probably by the mechanism of inhibition of EC proliferation and promotion of
      their apoptosis, furtherly, which may contribute to the apoptosis of tumor cells
      and result in suppression of tumor growth.

PMID- 11955425
TI  - Fusion and fission: membrane trafficking in animal cytokinesis.
AB  - Cytokinesis is the physical act of separating daughter cells, allowing them to
      become separate entities. Recent studies have revealed that membrane insertion
      for furrowing and scission of the residual bridge is a key aspect of animal
      cytokinesis.

PMID- 11955426
TI  - Walking the walk: migration and other common themes in blood and vascular
      development.
AB  - In this issue of Cell, a study by N. Cho and coworkers provides insight into the
      role of vascular endothelial growth factor (VEGF) signaling in Drosophila
      hematopoiesis. Their work suggests that an ancestral function of VEGF was to
      guide blood cell migration and highlights the conservation of at least one aspect
      of VEGF signaling during evolution.

PMID- 11955427
TI  - Pheromones, vomeronasal function, and gender-specific behavior.
AB  - The striking behavioral phenotypes of mice lacking the TRP2 ion channel have
      highlighted the importance of the vomeronasal organ in gender-specific sexual
      behavior.

PMID- 11955428
TI  - Calmodulin in action: diversity in target recognition and activation mechanisms.
AB  - Recent structural studies on calmodulin complexes with anthrax adenylyl cyclase
      and rat Ca2+-activated K+ channel have uncovered unexpected ways by which
      calmodulin interacts with target proteins.

PMID- 11955429
TI  - RIN4 interacts with Pseudomonas syringae type III effector molecules and is
      required for RPM1-mediated resistance in Arabidopsis.
AB  - In Arabidopsis, RPM1 confers resistance against Pseudomonas syringae expressing
      either of two sequence unrelated type III effectors, AvrRpm1 or AvrB. An RPM1
      interacting protein (RIN4) coimmunoprecipitates from plant cell extracts with
      AvrB, AvrRpm1, or RPM1. Reduction of RIN4 protein levels inhibits both the
      hypersensitive response and the restriction of pathogen growth controlled by
      RPM1. RIN4 reduction causes diminution of RPM1. RIN4 reduction results in
      heightened resistance to virulent Peronospora parasitica and P. syringae, and
      ectopic defense gene expression. Thus, RIN4 positively regulates RPM1-mediated
      resistance yet is, formally, a negative regulator of basal defense responses.
      AvrRpm1 and AvrB induce RIN4 phosphorylation. This may enhance RIN4 activity as a
      negative regulator of plant defense, facilitating pathogen growth. RPM1 may
      "guard" against pathogens that use AvrRpm1 and AvrB to manipulate RIN4 activity.

PMID- 11955430
TI  - CD83 expression influences CD4+ T cell development in the thymus.
AB  - T lymphocyte selection and lineage commitment in the thymus requires multiple
      signals. Herein, CD4+ T cell generation required engagement of CD83, a surface
      molecule expressed by thymic epithelial and dendritic cells. CD83-deficient (CD83
      /-) mice had a specific block in CD4+ single-positive thymocyte development
      without increased CD4+CD8+ double- or CD8+ single-positive thymocytes. This
      resulted in a selective 75%-90% reduction in peripheral CD4+ T cells,
      predominantly within the naive subset. Wild-type thymocytes and bone marrow stem
      cells failed to differentiate into mature CD4+ T cells when transferred into CD83
      /- mice, while CD83-/- thymocytes and stem cells developed normally in wild-type
      mice. Thereby, CD83 expression represents an additional regulatory component for
      CD4+ T cell development in the thymus.

PMID- 11955431
TI  - Structure of the C3b binding site of CR1 (CD35), the immune adherence receptor.
AB  - Complement receptor type 1 (CR1 or CD35) is a multiple modular protein that
      mediates the immune adherence phenomenon, a fundamental event for destroying
      microbes and initiating an immunological response. It fulfills this role through
      binding C3b/C4b-opsonized foreign antigens. The structure of the principal
      C3b/C4b binding site (residues 901-1095) of CR1 is reported, revealing three
      complement control protein modules (modules 15-17) in an extended head-to-tail
      arrangement with flexibility at the 16-17 junction. Structure-guided mutagenesis
      identified a positively charged surface region on module 15 that is critical for
      C4b binding. This patch, together with basic side chains of module 16 exposed on
      the same face of CR1, is required for C3b binding. These studies reveal the
      initial structural details of one of the first receptor-ligand interactions to be
      identified in immunobiology.

PMID- 11955432
TI  - Hairpin opening and overhang processing by an Artemis/DNA-dependent protein
      kinase complex in nonhomologous end joining and V(D)J recombination.
AB  - Mutations in the Artemis protein in humans result in hypersensitivity to DNA
      double-strand break-inducing agents and absence of B and T lymphocytes
      (radiosensitive severe combined immune deficiency [RS-SCID]). Here, we report
      that Artemis forms a complex with the 469 kDa DNA-dependent protein kinase (DNA
      PKcs) in the absence of DNA. The purified Artemis protein alone possesses single
      strand-specific 5' to 3' exonuclease activity. Upon complex formation, DNA-PKcs
      phosphorylates Artemis, and Artemis acquires endonucleolytic activity on 5' and
      3' overhangs, as well as hairpins. Finally, the Artemis:DNA-PKcs complex can open
      hairpins generated by the RAG complex. Thus, DNA-PKcs regulates Artemis by both
      phosphorylation and complex formation to permit enzymatic activities that are
      critical for the hairpin-opening step of V(D)J recombination and for the 5' and
      3' overhang processing in nonhomologous DNA end joining.

PMID- 11955433
TI  - Crystal structure of the Bacillus stearothermophilus anti-sigma factor SpoIIAB
      with the sporulation sigma factor sigmaF.
AB  - Cell type-specific transcription during Bacillus sporulation is established by
      sigmaF. SpoIIAB is an anti-sigma that binds and negatively regulates sigmaF, as
      well as a serine kinase that phosphorylates and inactivates the anti-anti-sigma
      SpoIIAA. The crystal structure of sigmaF bound to the SpoIIAB dimer in the low
      affinity, ADP form has been determined at 2.9 A resolution. SpoIIAB adopts the
      GHKL superfamily fold of ATPases and histidine kinases. A domain of sigmaF
      contacts both SpoIIAB monomers, while 80% of the sigma factor is disordered. The
      interaction occludes an RNA polymerase binding surface of sigmaF, explaining the
      SpoIIAB anti-sigma activity. The structure also explains the specificity of
      SpoIIAB for its target sigma factors and, in combination with genetic and
      biochemical data, provides insight into the mechanism of SpoIIAA anti-anti-sigma
      activity.

PMID- 11955434
TI  - P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange
      factor for Rac.
AB  - Rac, a member of the Rho family of monomeric GTPases, is an integrator of
      intracellular signaling in a wide range of cellular processes. We have purified a
      PtdIns(3,4,5)P3-sensitive activator of Rac from neutrophil cytosol. It is an
      abundant, 185 kDa guanine-nucleotide exchange factor (GEF), which we cloned and
      named P-Rex1. The recombinant enzyme has Rac-GEF activity that is directly,
      substantially, and synergistically activated by PtdIns(3,4,5)P3 and Gbetagammas
      both in vitro and in vivo. P-Rex1 antisense oligonucleotides reduced endogenous P
      Rex1 expression and C5a-stimulated reactive oxygen species formation in a
      neutrophil-like cell line. P-Rex1 appears to be a coincidence detector in
      PtdIns(3,4,5)P3 and Gbetagamma signaling pathways that is particularly adapted to
      function downstream of heterotrimeric G proteins in neutrophils.

PMID- 11955435
TI  - Proteolysis of the Hedgehog signaling effector Cubitus interruptus requires
      phosphorylation by Glycogen Synthase Kinase 3 and Casein Kinase 1.
AB  - The secreted signaling molecule Hedgehog regulates gene expression in target
      cells in part by preventing proteolysis of the full-length Cubitus interruptus
      (Ci-155) transcriptional activator to the Ci-75 repressor form. Ci-155
      proteolysis depends on phosphorylation at three sites by Protein Kinase A (PKA).
      We show that these phosphoserines prime further phosphorylation at adjacent
      Glycogen Synthase Kinase 3 (GSK3) and Casein Kinase I (CK1) sites. Alteration of
      the GSK3 or CK1 sites prevents Ci-155 proteolysis and activates Ci in the absence
      of Hedgehog. Ci-155 proteolysis is also inhibited if cells lack activity of the
      Drosophila GSK3, Shaggy, previously implicated in Wingless signaling. Conversely,
      Ci-155 levels are reduced in Hedgehog-responding cells by overexpression of PKA
      and the Drosophila CK1, Double-time, a regulator of circadian rhythms.

PMID- 11955436
TI  - Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism.
AB  - Wnt regulation of beta-catenin degradation is essential for development and
      carcinogenesis. beta-catenin degradation is initiated upon amino-terminal
      serine/threonine phosphorylation, which is believed to be performed by glycogen
      synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and
      adnomatous polyposis coli (APC). Here we describe another Axin-associated kinase,
      whose phosphorylation of beta-catenin precedes and is required for subsequent GSK
      3 phosphorylation of beta-catenin. This "priming" kinase is casein kinase Ialpha
      (CKIalpha). Depletion of CKIalpha inhibits beta-catenin phosphorylation and
      degradation and causes abnormal embryogenesis associated with excessive Wnt/beta
      catenin signaling. Our study uncovers distinct roles and steps of beta-catenin
      phosphorylation, identifies CKIalpha as a component in Wnt/beta-catenin
      signaling, and has implications to pathogenesis/therapeutics of human cancers and
      diabetes.

PMID- 11955437
TI  - Synaptic strength regulated by palmitate cycling on PSD-95.
AB  - Dynamic regulation of AMPA-type glutamate receptors represents a primary
      mechanism for controlling synaptic strength, though mechanisms for this process
      are poorly understood. The palmitoylated postsynaptic density protein, PSD-95,
      regulates synaptic plasticity and associates with the AMPA receptor trafficking
      protein, stargazin. Here, we identify palmitate cycling on PSD-95 at the synapse
      and find that palmitate turnover on PSD-95 is regulated by glutamate receptor
      activity. Acutely blocking palmitoylation disperses synaptic clusters of PSD-95
      and causes a selective loss of synaptic AMPA receptors. We also find that rapid
      glutamate-mediated AMPA receptor internalization requires depalmitoylation of PSD
      95. In a nonneuronal model system, clustering of PSD-95, stargazin, and AMPA
      receptors is also regulated by ongoing palmitoylation of PSD-95 at the plasma
      membrane. These studies suggest that palmitate cycling on PSD-95 can regulate
      synaptic strength and regulates aspects of activity-dependent plasticity.

PMID- 11955439
TI  - Does artemis end the hunt for the hairpin-opening activity in V(D)J
      recombination?
AB  - When complexed with the catalytic subunit of DNA-dependent protein kinase (DNA
      PK(cs)), the recently discovered dsDNA break repair protein named Artemis
      acquires the ability to open hairpin DNA molecules in vitro. Both genetic and
      biochemical data point toward a physiological role for this complex as the
      elusive hairpin-opening activity in V(D)J recombination.

PMID- 11955438
TI  - Developmental control of blood cell migration by the Drosophila VEGF pathway.
AB  - We show that a vascular endothelial growth factor (VEGF) pathway controls
      embryonic migrations of blood cells (hemocytes) in Drosophila. The VEGF receptor
      homolog is expressed in hemocytes, and three VEGF homologs are expressed along
      hemocyte migration routes. A receptor mutation arrests progression of blood cell
      movement. Mutations in Vegf17E or Vegf27Cb have no effect, but simultaneous
      inactivation of all three Vegf genes phenocopied the receptor mutant, and ectopic
      expression of Vegf27Cb redirected migration. Genetic experiments indicate that
      the VEGF pathway functions independently of pathways governing hemocyte homing on
      apoptotic cells. The results suggest that the Drosophila VEGF pathway guides
      developmental migrations of blood cells, and we speculate that the ancestral
      function of VEGF pathways was to guide blood cell movement.

PMID- 11955440
TI  - Antigenic variation and allelic exclusion.
AB  - Cells often express only one gene from a set of two or more. African trypanosomes
      appear to accomplish this monoallelic expression by segregating the selected gene
      into a specific nuclear body. The possibility that such a structure might explain
      monoallelic expression in other multigene systems is discussed here.

PMID- 11955441
TI  - Integrating functions at the kinetochore.
AB  - Kinetochore components have catalytic as well as structural activities. New
      evidence illustrates how these proteins integrate spindle morphogenesis with
      regulation of the timing and accuracy of chromosome segregation.

PMID- 11955443
TI  - Correction of a genetic defect by nuclear transplantation and combined cell and
      gene therapy.
AB  - Immune-deficient Rag2(-/-) mice were used as nuclear donors for transfer into
      enucleated oocytes, and the resulting blastocysts were cultured to isolate an
      isogenic embryonic stem cell line. One of the mutated alleles in the Rag2(-/-) ES
      cells was repaired by homologous recombination, thereby restoring normal Rag2
      gene structure. Mutant mice were treated with the repaired ES cells in two ways.
      (1) Immune-competent mice were generated from the repaired ES cells by tetraploid
      embryo complementation and were used as bone marrow donors for transplantation.
      (2) Hematopoietic precursors were derived by in vitro differentiation from the
      repaired ES cells and engrafted into mutant mice. Mature myeloid and lymphoid
      cells as well as immunoglobulins became detectable 3-4 weeks after
      transplantation. Our results establish a paradigm for the treatment of a genetic
      disorder by combining therapeutic cloning with gene therapy.

PMID- 11955444
TI  - HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem
      cell and yolk sac hematopoietic progenitors.
AB  - The extent to which primitive embryonic blood progenitors contribute to
      definitive lymphoid-myeloid hematopoiesis in the adult remains uncertain. In an
      effort to characterize factors that distinguish the definitive adult
      hematopoietic stem cell (HSC) and primitive progenitors derived from yolk sac or
      embryonic stem (ES) cells, we examined the effect of ectopic expression of HoxB4,
      a homeotic selector gene implicated in self-renewal of definitive HSCs.
      Expression of HoxB4 in primitive progenitors combined with culture on
      hematopoietic stroma induces a switch to the definitive HSC phenotype. These
      progenitors engraft lethally irradiated adults and contribute to long-term,
      multilineage hematopoiesis in primary and secondary recipients. Our results
      suggest that primitive HSCs are poised to become definitive HSCs and that this
      transition can be promoted by HoxB4 expression. This strategy for blood
      engraftment enables modeling of hematopoietic transplantation from ES cells.

PMID- 11955445
TI  - HOXB4-induced expansion of adult hematopoietic stem cells ex vivo.
AB  - Hox transcription factors have emerged as important regulators of primitive
      hematopoietic cell proliferation and differentiation. In particular, HOXB4
      appears to be a strong positive regulator of hematopoietic stem cell (HSC) self
      renewal. Here we demonstrate the potency of HOXB4 to enable high-level ex vivo
      HSC expansion. Cultures of nontransduced or GFP-transduced murine bone marrow
      cells experienced large HSC losses over 10-14 days. In sharp contrast, cultures
      of HOXB4-transduced cells achieved rapid, extensive, and highly polyclonal HSC
      expansions, resulting in over 1000-fold higher levels relative to controls and a
      40-fold net HSC increase. Importantly, these HSCs retained full lympho-myeloid
      repopulating potential and enhanced in vivo regenerative potential, demonstrating
      the feasibility of achieving significant ex vivo expansion of HSCs without
      functional impairment.

PMID- 11955446
TI  - Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to
      the nuclear beta-catenin-TCF complex.
AB  - Wnt/Wingless signaling controls many fundamental processes during animal
      development. Wnt transduction is mediated by the association of beta-catenin with
      nuclear TCF DNA binding factors. Here we report the identification of two segment
      polarity genes in Drosophila, legless (lgs), and pygopus (pygo), and we show that
      their products are required for Wnt signal transduction at the level of nuclear
      beta-catenin. Lgs encodes the homolog of human BCL9, and we provide genetic and
      molecular evidence that these proteins exert their function by physically linking
      Pygo to beta-catenin. Our results suggest that the recruitment of Pygo permits
      beta-catenin to transcriptionally activate Wnt target genes and raise the
      possibility that a deregulation of these events may play a causal role in the
      development of B cell malignancies.

PMID- 11955447
TI  - The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype
      specification.
AB  - OLIG1 and OLIG2 are basic-helix-loop-helix (bHLH) transcription factors expressed
      in the pMN domain of the spinal cord, which sequentially generates motoneurons
      and oligodendrocytes. In Olig1/2 double-mutant mice, motoneurons are largely
      eliminated, and oligodendrocyte differentiation is abolished. Lineage tracing
      data suggest that Olig1(-/-)2(-/-) pMN progenitors instead generate V2
      interneurons and then astrocytes. This apparent conversion likely reflects
      independent roles for OLIG1/2 in specifying motoneuron and oligodendrocyte fates.
      Olig genes therefore couple neuronal and glial subtype specification, unlike
      proneural bHLH factors that control the neuron versus glia decision. Our results
      suggest that in the spinal cord, Olig and proneural genes comprise a
      combinatorial code for the specification of neurons, astrocytes, and
      oligodendrocytes, the three fundamental cell types of the central nervous system.

PMID- 11955448
TI  - Common developmental requirement for Olig function indicates a motor
      neuron/oligodendrocyte connection.
AB  - The oligodendrocyte lineage genes Olig1 and Olig2 encode related bHLH proteins
      that are coexpressed in neural progenitors. Targeted disruption of these two
      genes sheds light on the ontogeny of oligodendroglia and genetic requirements for
      their development from multipotent CNS progenitors. Olig2 is required for
      oligodendrocyte and motor neuron specification in the spinal cord. Olig1 has
      roles in development and maturation of oligodendrocytes, evident especially
      within the brain. Both Olig genes contribute to neural pattern formation. Neither
      Olig gene is required for astrocytes. These findings, together with fate mapping
      analysis of Olig-expressing cells, indicate that oligodendrocytes are derived
      from Olig-specified progenitors that give rise also to neurons.

PMID- 11955449
TI  - Expansion of the cell plate in plant cytokinesis requires a kinesin-like
      protein/MAPKKK complex.
AB  - The tobacco mitogen-activated protein kinase kinase kinase NPK1 regulates lateral
      expansion of the cell plate at cytokinesis. Here, we show that the kinesin-like
      proteins NACK1 and NACK2 act as activators of NPK1. Biochemical analysis suggests
      that direct binding of NACK1 to NPK1 stimulates kinase activity. NACK1 is
      accumulated specifically in M phase and colocalized with NPK1 at the phragmoplast
      equator. Overexpression of a truncated NACK1 protein that lacks the motor domain
      disrupts NPK1 concentration at the phragmoplast equator and cell plate formation.
      Incomplete cytokinesis is also observed when expression of NACK1 and NACK2 is
      repressed by virus-induced gene silencing and in embryonic cells from Arabidopsis
      mutants in which a NACK1 ortholog is disrupted. Thus, we conclude that expansion
      of the cell plate requires NACK1/2 to regulate the activity and localization of
      NPK1.

PMID- 11955450
TI  - Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter
      release.
AB  - We have identified mutations in Drosophila endophilin to study its function in
      vivo. Endophilin is required presynaptically at the neuromuscular junction, and
      absence of Endophilin dramatically impairs endocytosis in vivo. Mutant larvae
      that lack Endophilin fail to take up FM1-43 dye in synaptic boutons, indicating
      an inability to retrieve synaptic membrane. This defect is accompanied by an
      expansion of the presynaptic membrane, and a depletion of vesicles from the
      bouton lumen. Interestingly, mutant larvae are still able to sustain release at
      15%-20% of the normal rate during high-frequency stimulation. We propose that
      kiss-and-run maintains neurotransmission at active zones of the larval NMJ in
      endophilin animals.

PMID- 11955451
TI  - Causal relationship between the loss of RUNX3 expression and gastric cancer.
AB  - Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to
      stimulated proliferation and suppressed apoptosis in epithelial cells, and the
      cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF
      beta, indicating that Runx3 is a major growth regulator of gastric epithelial
      cells. Between 45% and 60% of human gastric cancer cells do not significantly
      express RUNX3 due to hemizygous deletion and hypermethylation of the RUNX3
      promoter region. Tumorigenicity of human gastric cancer cell lines in nude mice
      was inversely related to their level of RUNX3 expression, and a mutation (R122C)
      occurring within the conserved Runt domain abolished the tumor-suppressive effect
      of RUNX3, suggesting that a lack of RUNX3 function is causally related to the
      genesis and progression of human gastric cancer.

PMID- 11955454
TI  - Epidemiology of viral respiratory infections.
AB  - Acute respiratory tract infections are the most common illnesses in all
      individuals, regardless of age or gender. Epidemiologic surveys and community
      based studies conducted since the beginning of the 20th century have determined
      the rates of illness and the pathogens involved in such infections. These studies
      have shown that rhinoviruses cause the great majority of these respiratory
      illnesses, and their findings have examined the means of transmission of
      respiratory illness. More recently, advances in diagnostic techniques have
      enabled more complete identification of the viruses involved in respiratory
      infections, which has aided in the ability to direct specific therapeutic agents
      at the causative pathogens.

PMID- 11955452
TI  - XPD mutations prevent TFIIH-dependent transactivation by nuclear receptors and
      phosphorylation of RARalpha.
AB  - Inherited mutations in the XPD subunit of the general transcription/repair factor
      TFIIH yield the rare genetic disorder Xeroderma pigmentosum (XP), the phenotypes
      of which cannot be explained solely on the basis of a DNA repair defect. In cells
      derived from XP-D patients, we observed a reduction of the ligand-dependent
      transactivation mediated by several nuclear receptors (RARalpha, ERalpha, and
      AR). We demonstrate that the XPD mutation alters cdk7 function in RARalpha
      phosphorylation. Transactivation is restored upon overexpression of either the
      wild-type XPD or the RARalphaS77E (a mutation which mimics phosphorylated
      RARalpha). Thus, we demonstrate that the cdk7 kinase of TFIIH phosphorylates the
      nuclear receptor, then allowing ligand-dependent control of the activation of the
      hormone-responsive genes.

PMID- 11955455
TI  - Clinical significance and pathogenesis of viral respiratory infections.
AB  - Viral respiratory tract infections, also known as colds, are the most common
      infection in humans. The majority of these infections are caused by rhinoviruses.
      Rhinovirus deposition in the nose or the eye initiates infection. The virus
      attaches to the host cell intercellular adhesion molecule-1 (ICAM-1) receptors in
      the back of the throat. Subsequent viral replication triggers the release of
      inflammatory mediators and activation of neurogenic pathways, which lead to
      symptoms. Symptoms occur within 10 to 16 hours after virus entry into the nose
      and peak on days 2 to 3 of infection. Symptom duration is typically 1 week,
      although 25% of cases last longer. Understanding the chronology of these events
      is important in the timing of treatment. Because of the rapidity of symptom
      onset, early treatment is the key to reducing viral replication and illness.
      Also, early treatment may reduce the risk of transmission.

PMID- 11955456
TI  - Rhinovirus respiratory infections and asthma.
AB  - Viral infections, particularly respiratory illnesses caused by rhinovirus, are
      the most common cause of asthma exacerbations in children and contribute in large
      part to asthma morbidity in adults. Epidemiologic studies and increasingly
      sophisticated viral detection methodologies have helped to define the role of
      rhinovirus as a potential causative agent in asthma exacerbations. Rhinovirus
      induced lung disease is multifaceted and can be characterized in terms of a
      variety of physiologic, immunologic, and viral processes. The precise direct and
      indirect mechanisms of viral contribution to exacerbations must still be
      elucidated. Understanding them will have an impact on the design of future
      treatment modalities.

PMID- 11955457
TI  - Viral respiratory infections in elderly patients and patients with chronic
      obstructive pulmonary disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) and elderly
      individuals are prone to the development of significant lower respiratory tract
      symptoms from colds caused by viral respiratory pathogens. Longitudinal
      surveillance studies conducted to assess the impact of viral respiratory tract
      pathogens on morbidity and mortality in each of these at-risk populations
      demonstrate that there is a substantial burden of disease from viral respiratory
      infection (VRI), including rhinovirus infections, with respect to utilization of
      health-care resources. Despite a similar rate of occurrence of VRI among subjects
      with COPD and the control group, a cohort with moderate to severe COPD had a 2
      fold increase in medical resource utilization, including clinician visits,
      emergency center visits, and hospitalizations. In surveillance studies of
      respiratory viruses in the elderly, regular seasonal infections with rhinoviruses
      cause substantial morbidity, which has been largely underappreciated and
      underreported.

PMID- 11955458
TI  - Viral respiratory infection therapy: historical perspectives and current trials.
AB  - Attempts to relieve the misery of the common cold have been made since long
      before current understanding of its viral origin. Although current symptomatic
      therapies provide some relief, any effective treatment must incorporate an
      antiviral to address the infection. Symptom production is related not only to
      viral cytopathic effect but also to the early activation of several inflammatory
      pathways. Antiviral treatment alone may not be able to prevent these events.
      Combining an antiviral with selected therapeutic agents that block these
      inflammatory pathways has been shown to improve the effectiveness of cold
      treatment. Early diagnosis and initiation of treatment combined with regular
      dosing until symptoms subside appears to be the most effective treatment strategy
      to maximize therapeutic outcomes. This strategy reduces viral shedding in nasal
      fluid, provides treatment for the period of maximum symptom burden, and may
      reduce the frequency and severity of the sinus disease that accompanies colds.

PMID- 11955459
TI  - Cost burden of viral respiratory infections: issues for formulary decision
      makers.
AB  - Viral respiratory infections (VRIs) are a common malady associated with
      considerable costs in terms of decreased productivity and time lost from work or
      school, visits to health-care providers, and the amount of drugs prescribed. Both
      total respiratory illness and rhinovirus infection peak during the fall and
      spring seasons, although the average percentage of office visits by patients with
      a rhinovirus infection is moderately high throughout the year. Most common cold
      remedies are relatively ineffective and may produce side effects that contribute
      to increased health-care costs. Antibiotic therapy is widely overused and misused
      despite evidence that antibiotics fail to treat the cause of VRI or prevent
      secondary bacterial infections. Increasing use of antibiotics has a significant
      impact on health-care costs and the emergence of antimicrobial resistance.
      Reasons for overprescribing antibiotics are varied, but they often involve
      physician and patient attitudes and expectations. Although treatment of VRIs
      poses challenges for effective formulary management, several steps can be taken
      to facilitate the introduction of antiviral agents, including patient and
      provider education, the development of rapid diagnostic tests, and medical
      economics studies to determine the true cost of antiviral therapy.

PMID- 11955460
TI  - Brain maturation may be arrested in chronic cocaine addicts.
AB  - BACKGROUND: Animal and human newborn studies suggest that exposure to cocaine in
      utero delays glial maturation and white matter myelination. Postmortem data show
      that in the frontal and temporal lobes, white matter myelination continues into
      middle age. Recent magnetic resonance imaging (MRI) data have confirmed continued
      white matter volume increase in these regions, reaching a maximum at age 47.
      METHODS: Thirty-seven male cocaine dependent (CD) and 52 normal control subjects
      between ages 19 and 47 were evaluated with MRI. Coronal images focused on the
      frontal and temporal lobes were acquired using pulse sequences that maximized
      gray/white matter contrast. RESULTS: Highly significant positive correlations
      between white matter volume and age were observed in both the frontal and
      temporal lobes of the control group (r =.52, p =.0001 and r =.54, p =.0001,
      respectively); however, CD subjects did not demonstrate any age-related increase
      in white matter volume of the frontal (r = -.001; p =.99) and temporal (r = -.07;
      p =.67) lobes in this age range. CONCLUSIONS: The age-related expansion in white
      matter volume occurring in normal control subjects was absent in CD subjects. The
      findings suggest that in adults, cocaine dependence may arrest normal white
      matter maturation in the frontal and temporal lobes of addicts who continue using
      cocaine.

PMID- 11955461
TI  - Reduction of cocaine place preference in mice lacking the protein phosphatase 1
      inhibitors DARPP 32 or Inhibitor 1.
AB  - BACKGROUND: Modulation of protein phosphorylation by dopamine is thought to play
      an important role in drug reward. Protein phosphatase-1 (PP-1) is known to
      mediate some of the changes in neuronal signaling that occur following activation
      of the dopaminergic system. METHODS: Two endogenous inhibitors of PP-1 are
      dopamine and cyclic 3', 5' adenosine monophosphate-regulated phosphoprotein
      (DARPP-32) and Inhibitor-1 (I-1). Knockout mice lacking one or both of these PP-1
      inhibitors were tested for responses to cocaine using in vivo amperometry and
      conditioned place preference. RESULTS: Presynaptic dopaminergic function appears
      to be unaffected by these mutations because stimulation-evoked changes in
      extracellular dopamine levels were unchanged between wild type mice and mice
      lacking one or both of these PP-1 inhibitors. In contrast, conditioned place
      preference to cocaine is reduced in mice lacking DARPP-32, I-1, or both
      phosphoproteins. This does not appear to be due to a learning deficit because
      mice lacking both DARPP-32 and I-1 show normal passive avoidance learning.
      CONCLUSIONS: These data imply that increased PP-1 function as a result of
      deficits in DARPP-32 or I-1 is sufficient to decrease the rewarding properties of
      cocaine. Furthermore, the mechanism for this altered cocaine place preference
      does not involve alteration of dopamine release or reuptake.

PMID- 11955463
TI  - Sleep deprivation as a probe of homeostatic sleep regulation in primary
      alcoholics.
AB  - BACKGROUND: Alcoholic patients show prominent disturbances of sleep
      electroencephalograms (EEGs) with a marked loss of slow wave sleep that is even
      more profound in African American alcoholics as compared to European Americans.
      Using partial sleep deprivation, this study examined the extent to which abnormal
      sleep is reversible in alcoholic subjects. METHODS: In a sample stratified on
      ethnicity, polysomnographic and spectral sleep EEG measures were compared in male
      primary alcoholic in patients (n=46) and age-matched comparison controls (n=32)
      at baseline-and recovery sleep following a night of partial sleep deprivation.
      RESULTS: As compared to controls, alcoholic patients showed a loss of slow wave
      sleep and more spectral power in beta frequencies. Following sleep deprivation,
      slow wave sleep and delta power differentially changed between the groups.
      European American controls showed increases of slow wave sleep that were more
      robust than responses found in African American controls, whereas both alcoholic
      groups failed to show increases of slow wave sleep from baseline to recovery.
      Spectral EEG analyses revealed similar results; sleep deprivation induced
      significant increases of delta power during NREM-1 in the controls, but not in
      the alcoholics. CONCLUSIONS: Alcohol dependence compromises the augmentation of
      slow wave sleep and delta power seen in healthy adults following sleep
      deprivation. The differential effect of alcoholism on sleep stage physiology
      suggests a defect in the regulation or plasticity of slow wave sleep with
      implications for theories linking sleep depth to morbidity and outcome in
      alcoholics.

PMID- 11955462
TI  - Neurodevelopmental patterns of visual P3b in association with familial risk for
      alcohol dependence and childhood diagnosis.
AB  - BACKGROUND: The P3b component of the event-related potential (ERP) has frequently
      been reported to be reduced in children and adolescents at high risk for
      developing alcoholism relative to control children and adolescents without
      familial loading for alcohol dependence. P300 amplitude changes during
      development for all children. Previously it has been shown that high-risk
      offspring display a pattern in which the amplitude is lower at age 8 with a
      smaller rate of change during adolescence. METHODS: Admixture analysis was
      applied to data obtained for those children and adolescents having five or more
      annual assessments of ERPs to determine if multiple P3b growth patterns exist.
      The P3b amplitude patterns obtained were related to risk status, concurrent
      presence of childhood psychopathology (internalizing or externalizing), and age
      of onset to develop a diagnosis. RESULTS: A pattern characterized by lower P3b
      amplitude at study entry and a slower rate of change during child and adolescent
      development (pattern 3) was most often associated with high-risk status in boys
      and high-risk status in combination with the presence of a childhood diagnosis in
      girls. Pattern 3 was significantly related to the overall presence of childhood
      psychopathology (internalizing or externalizing) and to the presence of an Axis I
      diagnosis at young adult follow-up. CONCLUSIONS: The developmental pattern
      previously described for offspring at high risk for developing alcoholism because
      of their familial/genetic background was confirmed. Admixture analysis has
      refined this observation and suggests that among all children and adolescents
      tested, three developmental patterns can be identified, one of which is most
      often seen in association with male high-risk children and adolescents.

PMID- 11955464
TI  - Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients.
AB  - BACKGROUND: Alteration in noradrenergic regulation as well as alteration in the
      hypothalamic-pituitary-adrenal (HPA) axis have been associated with opioid
      dependence and acute abstinence symptoms. METHODS: This double-blind, placebo
      controlled study evaluated subjective, physiologic, and biochemical responses to
      yohimbine (.4 mg/kg, IV) in eight patients receiving methadone and compared
      results to those from a pool of nine healthy volunteers. All subjects were
      compared for panic anxiety symptom scale (PASS) scores, systolic and diastolic
      blood pressure, heart rate, plasma 3-methoxy-4 hydroxyphenethyleneglycol (MHPG),
      and cortisol. RESULTS: Yohimbine elicited objective and subjective opioid
      withdrawal and elevated craving for opioid drugs in methadone patients.
      Significant yohimbine effects were seen across the combined subject group for
      PASS, physiologic measures, MHPG, and cortisol. Methadone patients had lower
      baseline MHPG levels. Methadone group interactions with yohimbine were seen for
      systolic blood pressure and cortisol levels. CONCLUSIONS: Methadone-maintained
      patients are sensitive to the postsynaptic effects of noradrenergic-facilitating
      medications, experiencing greater physiologic and psychological symptoms,
      including an increase in craving. The effect on cortisol supports the above
      conclusion and is consistent with HPA axis perturbation in opioid dependence as
      reported in other studies and extends these observations to stable methadone
      maintained patients. Medications that increase synaptic noradrenaline should be
      used with care in opioid-dependent patients.

PMID- 11955465
TI  - Adrenocorticotropin and cortisol responses to a naloxone challenge and risk of
      alcoholism.
AB  - BACKGROUND: Because abnormalities in opioid neurotransmission appear to underlie
      some of the inherited risk for alcoholism, we examined the effects of naloxone,
      an opioid antagonist, on corticotropin and cortisol responses in nonalcoholic
      subjects differentiated by paternal history of alcoholism. METHODS: Placebo
      controlled, balanced, within-subject design involving 2 test days over a period
      of 3 to 7 days. Thirty-six subjects (67% male; 53% paternal-history-positive;
      mean age = 25.0 years) were screened to exclude substance abuse or dependence.
      Subjects received intravenous naloxone 125 microg/kg or placebo, with sessions in
      random order. Plasma corticotropin and cortisol were measured for up to 120 min
      post infusion. RESULTS: Corticotropin responses at baseline and following
      naloxone did not differ by paternal history of alcoholism; however, paternal
      history-positive subjects exhibited greater cortisol concentrations at baseline,
      and at 15 and 30 min after naloxone administration. Paternal-history-positive
      subjects also had an earlier and greater peak cortisol response to naloxone and a
      nonsignificant trend for a greater area under the cortisol time curve than
      paternal-history-negative subjects. CONCLUSIONS: These findings suggest that
      individuals with greater vulnerability to alcoholism may have altered
      Hypothalamic-pituitary axis (HPA) dynamics, a finding that is consistent with a
      growing body of data on the role of opioidergic neurotransmission in the
      inherited risk of alcoholism.

PMID- 11955466
TI  - Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for
      major depression: preliminary results of a randomized trial.
AB  - BACKGROUND: Many severely depressed patients do not benefit from or tolerate
      existing treatments. Repetitive transcranial magnetic stimulation (rTMS) has been
      reported to benefit depression. We compared rTMS to electroconvulsive therapy
      (ECT) in severely ill, depressed patients. METHODS: Twenty-five patients with a
      major depression (unipolar or bipolar) deemed clinically appropriate for ECT were
      randomly assigned to rTMS (10-20 treatments, 10 Hz, 110% motor threshold applied
      to the left dorsolateral prefrontal cortex for a total of 10,000-20,000
      stimulations) or a course of bitemporal ECT (4-12 treatments). The primary
      outcome measure was the 24-item Hamilton Depression Rating Scale (HDRS). The
      Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMS), and
      Clinical Global Impression scale (CGI) were secondary measures. Minimal rescue
      medications were utilized. RESULTS: Mean percent improvement on the baseline HDRS
      score did not significantly differ between the two treatments (i.e., 55% for the
      rTMS group vs. 64% for the ECT group [p = ns]). With response defined as a 50%
      reduction from baseline and a final score < or = 8 on the HDRS, there was also no
      significant difference between the two groups. We did not observe any differences
      between groups on the secondary measures. CONCLUSIONS: A 2-4 week randomized,
      prospective trial comparing rTMS to ECT produced comparable therapeutic effects
      in severely depressed patients.

PMID- 11955467
TI  - Inhibition in children with attention-deficit/hyperactivity disorder: a
      psychophysiological study of the stop task.
AB  - BACKGROUND: The purpose of the study was to investigate and identify abnormal
      brain activity, as revealed by event-related potentials (ERPs) concurring with
      deficient inhibitory control in children with attention-deficit/hyperactivity
      disorder (ADHD). METHODS: Performance and ERPs from 16 children with ADHD and 16
      control subjects were compared in the stop-signal paradigm. RESULTS: The ADHD
      children showed a lower inhibition percentage and their (estimated) response time
      to the stop signal was disproportionally longer compared to the slowing of
      reaction times to primary-task stimuli. In normal control subjects, fronto
      central positivity (100-400 msec) after the onset of the stop-signal was larger
      in case of successful inhibition, relative to failed inhibition; this was less so
      in ADHD children. A late positive wave (500-700 msec), maximal at Oz on failed
      inhibition trials, and possibly related to error-detection, was smaller in ADHD
      children. CONCLUSIONS: These results point to abnormalities in brain processes
      involved in motor inhibition and error-detection in ADHD children.

PMID- 11955468
TI  - Estrogen receptor 1 polymorphisms and risk of cognitive impairment in older
      women.
AB  - BACKGROUND: Several genes associated with sporadic Alzheimer's disease have been
      identified; however, approximately 50% of genetic factors remain unidentified. We
      investigated whether estrogen receptor 1 (ESR1) polymorphisms are associated with
      risk of developing cognitive impairment in older women. METHODS: A total of 2625
      women > or = 65 years of age completed a modified Mini-Mental Status Exam (mMMSE)
      at baseline and at 6-8 years of follow-up. We defined cognitive impairment as a
      mMMSE decline of > or = 3 points, follow-up score < or = 20, or a history of
      physician-diagnosed dementia. The ESR1 polymorphisms, PvuII (P or p) and XbaI (X
      or x), were coded so that the capital letter signifies the absence of the
      restriction site. RESULTS: Women with a p allele had a greater age, education,
      and baseline-score adjusted decline in mMMSE (for PP, Pp, and pp, respectively:.6
      +/-.1,.8 +/-.1, and.9 +/-.1 points, p for trend =.01); women with at least one x
      allele also had greater score decline (XX, Xx, and xx:.7 +/-.1,.7 +/-.1, and.9 +/
      .1 points, p for trend =.02). Six percent (n = 166) of the women developed
      cognitive impairment. Compared to those who did not develop impairment, more
      women who developed cognitive impairment had a p allele (62% vs. 56%, p =.03;
      adjusted odds ration (OR) = 1.33; 95% confidence interval [CI], 1.03-1.72) or an
      x allele (70% vs. 64%, p =.03; adjusted OR = 1.38; 95% CI, 1.06-1.81). There was
      no interaction with current estrogen use, or with serum estradiol level and ESR1
      polymorphisms (p >.10). CONCLUSIONS: Estrogen receptor 1 polymorphisms are
      associated with risk of developing cognitive impairment. More research is needed
      to determine the mechanism whereby ESR1 polymorphisms or linked genes influence
      cognitive function in older women.

PMID- 11955469
TI  - Sensory gating and psychosis vulnerability in cocaine-dependent individuals:
      preliminary data.
AB  - BACKGROUND: Factors increasing vulnerability of a cocaine user to develop
      psychotic symptoms are unknown. Deficits in sensory gating and attention, such as
      those occurring in idiopathic psychosis, might represent experimentally tractable
      factors contributing to vulnerability to cocaine-induced paranoia. METHODS:
      Severity of cocaine-induced paranoid symptoms was assessed with the Cocaine
      Experience Questionnaire (CEQ) in 30 abstinent cocaine-dependent individuals.
      Sensory gating was assessed in a paired-click auditory evoked potential paradigm
      (S1 and S2) using the S2/S1 attenuation ratio of the P50 evoked response as the
      primary outcome measure. The Wender-Utah Rating Scale (WURS) for attention
      deficit was also administered. RESULTS: Subjects were divided into those with
      high CEQ scores (n = 10) and those with low CEQ scores (n = 20). The mean P50
      ratios were significantly higher for the high CEQ subjects compared with the low
      CEQ group (F = 4.6, p <.04). The WURS did not correlate with the total CEQ but
      correlated with the CEQ Severity subscale, r =.432, p <.02. CONCLUSIONS: The data
      suggest that deficient P50 sensory gating and attention deficits may be
      associated with increased proneness to developing psychotic symptoms in the
      context of cocaine use. Further exploration of these factors seems warranted.

PMID- 11955470
TI  - Three and six-month outcome following courses of either ECT or rTMS in a
      population of severely depressed individuals--preliminary report.
AB  - BACKGROUND: Recent studies have strengthened the claim that repetitive
      transcranial magnetic stimulation (rTMS) is an effective treatment for major
      depression. The longitudinal outcome of TMS-treated patients, however, has not
      been described. We report on the 3- and 6-month outcomes of a group of patients
      treated with either electroconvulsive therapy (ECT) (n = 20) or (rTMS) (n = 21).
      METHODS: Patients diagnosed with major depressive disorder with or without
      psychotic features referred for ECT were randomly assigned to receive either ECT
      or rTMS. Forty-one patients who responded to either treatment constituted the
      sample. Patients were followed on a monthly basis and outcomes were determined
      with the Hamilton Rating Scale for Depression-17 items (HRSD) and the Global
      Assessment of Functioning (GAF) scales. Medications were routinely prescribed.
      RESULTS: There were no differences in the 6-month relapse rate between the
      groups. Overall, 20% of the patients relapsed (four from the ECT group and four
      from the rTMS group). Patients reported equally low and not significantly
      different scores in the HRSD (ECT group 8.4 +/- 5.6 and TMS group 7.9 +/- 7.1)
      and the GAF (ECT group 72.8 +/- 12 and TMS group 77.8 +/- 17.1) at the 6-month
      follow up. CONCLUSIONS: Patients treated with rTMS do as well as those treated
      with ECT at the 3- and 6-month follow-up points. These data suggest that the
      clinical gains obtained with rTMS last at least as long as those obtained with
      ECT.

PMID- 11955472
TI  - Laryngeal effects of stimulation of rostral and ventral pons in the anaesthetized
      rat.
AB  - In order to study the importance of two pontine regions modulating laryngeal
      resistance, electrical current or microinjections of glutamate (10-30 nl, 1-3
      nmol) were made into the pontine parabrachial complex and the A5 region in
      spontaneously breathing anaesthetized rats. Two distinct patterns of laryngeal
      and respiratory responses were elicited. An increase of subglottal pressure was
      accompanied with an expiratory facilitatory response consisted of a decrease in
      both respiratory rate and phrenic nerve activity. A decrease of subglottal
      pressure was accompanied with an inspiratory facilitatory response consisted of
      an increase in both respiratory rate and phrenic nerve activity. The modification
      of laryngeal calibre occurred during both respiratory phases in most cases. The
      concomitant cardiovascular changes of these responses were also analyzed.
      Controls using guanethidine to block autonomic responses which might interact
      with respiratory control were also made. Histological analysis of stimulation
      sites showed a topographical organization of these responses: laryngeal
      constriction was evoked from Kolliker-Fuse, medial parabrachial nuclei and A5
      region, whilst the laryngeal dilation was evoked from the lateral parabrachial
      nucleus.

PMID- 11955473
TI  - Release of cytochrome c into the extracellular space contributes to neuronal
      apoptosis induced by staurosporine.
AB  - The mitochondrial protein cytochrome c has been identified as one of the key
      signalling molecules of apoptosis. In the present study, we used primary neuronal
      cultures to investigate whether cytochrome c was released from the mitochondria
      into the cytosol and subsequently into the culture medium during staurosporine
      induced apoptosis and whether extracellular cytochrome c modulates the degree of
      damage caused by staurosporine. We found the cytochrome c content in the
      mitochondria decreased 24 h after and increased in the cytosol 8 h after
      staurosporine was added to the culture medium. The cytochrome c content of the
      culture medium increased from 8 h up to 24 h after starting the staurosporine
      treatment. In parallel with the release of cytochrome c into the culture medium,
      membrane leakage occurred as determined by the release of LDH. Addition of
      cytochrome c accelerated, whereas the addition of anti-cytochrome c antibodies
      reduced staurosporine-induced neuronal death suggesting a pro-apoptotic role of
      cytochrome c released into the culture medium. Under control conditions,
      extracellularly added cytochrome c (25 ng/ml), which was in the range of the
      amount of cytochrome c released from staurosporine-treated neurons into the
      culture medium, increased the percentage of apoptotic neurons to 30% compared
      with 18% in vehicle-treated controls. Our results suggest that the release of
      cytochrome c into the extracellular space contributes to neuronal apoptosis
      induced by staurosporine.

PMID- 11955471
TI  - Volumetric structural magnetic resonance imaging (MRI) of the rat hippocampus
      following kainic acid (KA) treatment.
AB  - An in vivo MRI study employing a high field (7T) magnet and a T1- and T2-weighted
      imaging sequence with subsequent histopathological evaluations was undertaken to
      develop and evaluate MRI-based volumetric measurements in the rat. The brain
      structures considered were the hippocampus, the cingulate cortex, the
      retrosplenial granular cortex and the ventricles. Control (n=3) and kainic acid
      (KA; n=4) treated rats were scanned 10 days following the manifestation of stage
      four seizures. The MRI images exhibited anatomical details (125 microm in-plane
      resolution) that enabled volumetric analysis with high intra-rater reliability.
      Volumetric analysis revealed that KA-treated rats had significantly smaller
      hippocampi, and a significant increase in ventricular size. The cingulate cortex
      and the retrosplenial granular cortex did not differ in volume between the two
      groups. The histological observations supported the MRI data showing neuronal
      loss and neuronal degeneration in CA1 and CA3 of the hippocampus, which was
      accompanied by strong microglia activation. These data demonstrate a reliable and
      valid method for the measurement of the rat hippocampus in vivo using MRI with a
      high field magnet, thereby providing a useful tool for future studies of rodent
      models of neuro-degenerative diseases.

PMID- 11955474
TI  - Effects of antioxidant, OPC-14117, on secondary cellular damage and behavioral
      deficits following cortical contusion in the rat.
AB  - In the present study, we examined the effects of OPC-14117, a superoxide radical
      scavenger, on the secondary cellular damage and cognitive dysfunction occurring
      in a rat model of cerebral contusion induced by a controlled cortical impact
      (CCI). Histological examinations revealed that the contusion necrosis volume
      reached 13.6+/-5.3 mm(3) in non-treated animals and declined to 1.9+/-0.6 mm(3)
      in OPC-14117-treated animals (P<0.01). The cell number of the CA3 region was
      120.0+/-12.4 cells/mm in the normal controls, 73.6+/-9.9 cells/mm in the non
      treated animals, and 111.2+/-10.2 cells/mm in the OPC-14117-treated animals,
      indicating that CCI-induced selective neuronal cell death in the CA3 region was
      attenuated by the OPC-14117 administration (P<0.01). The tissue osmolality, as
      determined with a vapor pressure osmometer, was 314.5+/-15.4 mmol/kg in the
      normal brain and increased to 426.0+/-20.1 mmol/kg at 12 h following CCI. The
      increase in tissue osmolality was significantly attenuated by OPC-14117
      administration (P<0.01). The OPC-14117 administration also attenuated the CCI
      induced cognitive deficits. The OPC-14117-treated animals showed a tendency to
      improve on the Morris water maze performance test. The impairment of the
      habituation of exploratory activity elicited by CCI was significantly attenuated
      by OPC-14117 administration (P<0.05). In conclusion, OPC-14117 may have a
      potential for decreasing secondary cellular damage due to traumatic brain injury
      since it is as efficacious as any other compound tested in this model.

PMID- 11955475
TI  - Allopregnanolone inhibits learning in the Morris water maze.
AB  - The progesterone metabolite allopregnanolone (3alpha-OH-5alpha-pregnane-20-one)
      inhibits neural functions, enhancing the GABA induced GABA(A) receptor
      activation. This effect is benzodiazepine like and benzodiazepines are known to
      impair memory. Acute effects of allopregnanolone on the hippocampus dependent
      spatial learning in the Morris water maze have not been studied. Adult male
      Wistar rats where injected (i.v.) with allopregnanolone (2 mg/kg), or vehicle,
      daily for 11 days. At 8 or 20 min after each injection, studies of place
      navigation were performed in the Morris water maze. Allopregnanolone
      concentrations in plasma and in nine different brain areas where analyzed by
      radioimmunoassay. The latency to find the platform was increased 8 min after the
      allopregnanolone injection, while normal learning was seen after 20 min. Swim
      speed did not differ between groups. A higher number of rats were swimming close
      to the pool wall (thigmotaxis) in the 8 min allopregnanolone group compared to
      the other groups. Allopregnanolone concentrations in the brain tissue at 8 min
      were 1.5 to 2.5 times higher then at 20 min after the allopregnanolone
      injections. After vehicle injections the brain concentrations of allopregnanolone
      were at control levels. Plasma concentrations of allopregnanolone followed the
      same pattern as in the brain, with the exception of an increase 8 min after
      vehicle injections. The natural progesterone metabolite allopregnanolone can
      inhibit learning in the Morris water maze, an effect not caused by motor
      impairment. The learning impairment might be due to a combination of changed
      swimming behavior and difficulties in navigation.

PMID- 11955476
TI  - Clinorotation-induced weightlessness influences the cytoskeleton of glial cells
      in culture.
AB  - During and after spaceflight astronauts experience neurophysiological
      alterations. To investigate if the impairment observed might be traced back to
      cytomorphology, we undertook a ground based research using a random positioning
      machine (clinostat) as a simulation method for microgravity. The outcome of the
      study was represented by cytoskeletal changes occurring in cultured glial cells
      (C(6) line) after 15 min, 30 min, 1 h, 20 h and 32 h under simulated
      microgravity. Glia is fundamental for brain function and it is essential for the
      normal health of the entire nervous system. Our data showed that after 30 min
      under simulated microgravity the cytoskeleton was damaged: microfilaments (F
      actin) and intermediate filaments (Vimentin, Glial Fibrillary Acidic Proteins
      GFAP) were highly disorganised, microtubules (alpha-tubulin) lost their radial
      array, the overall cellular shape was deteriorated, and the nuclei showed altered
      chromatin condensations and DNA fragmentation. This feature got less dramatic
      after 20 h of simulated microgravity when glial cells appeared to reorganise
      their cytoskeleton and mitotic figures were present. The research was carried out
      by immunohistochemistry using antibodies to alpha-tubulin, vimentin and GFAP, and
      cytochemical labelling of F-actin (Phalloidin-TRIC). The nuclei were stained with
      propidium iodide or 4,6-diamidino-2-phenylindole dihydrochloride (DAPI). The
      cells were observed at the conventional and/or the confocal laser scanning
      microscope. Samples were also observed at the scanning electron microscope (SEM).
      Our data showed that in weightlessness alterations occur already visible at the
      scale of the single cell; if this may lead to the neurophysiological problems
      observed in flight is yet to be established.

PMID- 11955477
TI  - Electron microscope study of blood-brain barrier opening induced by immunological
      targeting of the endothelial barrier antigen.
AB  - Barrier vessels in the central nervous system are lined with endothelial cells
      which constitute the blood-brain barrier (BBB) and show selective expression of
      certain biochemical markers. One of these, the endothelial barrier antigen (EBA),
      is specific to the rat. The exact role of EBA in the BBB is not known, although
      several studies have shown a correlation between the reduction in EBA expression
      in endothelial cells and the opening of the BBB. However, in these studies it was
      not possible to determine if EBA reduction was a primary event or was secondary
      to opening of the BBB. A recent light microscope study demonstrated that
      immunological targeting of EBA in vivo, by intravenous injection of a monoclonal
      antibody (anti-EBA), leads to acute and widespread opening of the BBB. In the
      current study we have employed this model together with tracer application and
      immunoperoxidase electron microscopy to determine the site of binding of the
      injected antibody and the route of opening of the BBB. The results showed that
      (a) the anti-EBA injected in vivo became bound to brain endothelial cells,
      principally to luminal membranes. (b) Endothelial cells showed widened
      intercellular junctions and increased cytoplasmic vesicles and vacuoles. (c) Many
      perivascular astrocytic processes were swollen. (d) The macromolecular tracer HRP
      was present in vesicles, vacuoles, widened paracellular clefts, the perivascular
      space and brain parenchyma. In conclusion, the in vivo targeting of EBA leads to
      opening of the BBB apparently via paracellular and transcellular routes. This
      model is useful for the study of vascular permeability in the CNS and
      experimental manipulation of the BBB. It may have a potential application in
      experimental studies on drug delivery throughout the CNS.

PMID- 11955478
TI  - Identification and functional characterization of the novel isoforms of bovine
      norepinephrine transporter produced by alternative splicing.
AB  - Analyzing variation of bovine norepinephrine transporter (NET) at the 3'-region
      by RT-PCR in the adrenal glands and the brain revealed four isoforms of NET
      produced by alternative splicing of four cassettes (C0, C1, C2 and C3) encoded by
      exons 12-15, designated bNET1a (C0-C1-C2, formerly designated bNET1), bNET1b (C0
      C2), bNET2a (C0-C1-C3) and bNET2b (C0-C3, formerly designated bNET2),
      respectively. Expression of these isoforms in COS-7 cells revealed that the
      isoforms that contain the C1 cassette encoded by exon 13 (bNET1a and bNET2a)
      showed a significant increase in [(3)H]norepinephrine uptake and [(3)H]nisoxetine
      binding, whereas the isoforms which lack the C1 cassette (bNET1b and bNET2b)
      failed to display those activities despite the selection of either exon 14 or
      exon 15. These results suggest that the region encoded by exon 13 is
      indispensable for NET functional expression.

PMID- 11955479
TI  - Intrathecal administration of 5-HT(3) receptor agonist modulates jaw muscle
      activity evoked by injection of mustard oil into the temporomandibular joint in
      the rat.
AB  - The effect of intrathecal administration of the 5-HT(3) receptor agonist 2-methyl
      5-hydroxytryptamine (2m-5HT) on jaw muscle activity evoked by mustard oil (MO)
      injection into the temporomandibular joint of anesthetized rats was examined. One
      microgram or 100 microg of 2m-5HT significantly enhanced or suppressed jaw muscle
      responses, respectively. Pre-administration of tropisetron, a 5-HT(3) receptor
      antagonist, attenuated the effect of 2m-5HT. These results indicate that
      activation of 5-HT(3) receptors can modulate trigeminal nociceptive responses.

PMID- 11955480
TI  - EMG discharge patterns during human grip movement are task-dependent and not
      modulated by muscle contraction modes: a transcranial magnetic stimulation (TMS)
      study.
AB  - Our previous study revealed that, during tonic muscle contraction, remarkable
      functional differences among intrinsic and extrinsic muscles were observed during
      two different grip movements, i.e., precision and power grips. To verify whether
      this evidence is true even under the phasic muscle contraction, magnetic
      stimulation was delivered over the left scalp while a normal human subject
      performed phasic precision or power grip responses of the right-hand fingers in a
      simple reaction time (SRT) paradigm. Magnetic stimulation delivered during the
      latent period revealed different cortico-motoneuronal excitations between the two
      grip responses. In particular, the contributions of extensor carpi radialis (ECR)
      muscle were definitely different between the two grip responses, although motor
      evoked potentials (MEPs) of first dorsal interosseous (FDI) prior to, and after
      EMG onset of movement initiation, were not different. These results were similar
      to previous results obtained during tonic muscle contraction. Thus, we have
      concluded that the task-dependent EMG discharge pattern in finger manipulation
      could not be modulated by muscle contraction modes.

PMID- 11955484
TI  - Charting the course of medical laboratories in a changing environment.
AB  - BACKGROUND: In recent decades, dramatic changes have occurred in the
      organization, number and type of tests, and role of medical laboratories in
      healthcare. The role of laboratory professionals has undergone a radical change,
      which calls for greater analytical accuracy, and more stringent test selection,
      and interpretation of results. METHODS: The ancillary role of clinical
      laboratories in the past was analyzed in order to understand why the change has
      taken place, and to identify old and new areas in which laboratory information is
      largely used for improving upon decision making for treatment, and patient
      management. RESULTS: The availability of real-time laboratory results and more
      effective tests, the enhanced clinical consulting role, the involvement in
      therapeutic decisions, the efforts to prevent rather than cure disease, the shift
      from anecdotal care to evidence-based medicine, and the assessment of outcome for
      laboratory tests have all contributed to the changing role and duties of medical
      laboratories. CONCLUSIONS: Crucial elements in sustaining the changes in the role
      and contribution of medical laboratories to a high-quality healthcare are the
      ability of laboratory professionals to: guarantee the quality of laboratory tests
      irrespective of where they are performed; improve the quality of services;
      improve clinical outcomes; and perform joint clinical/laboratory research
      projects. A key factor in effecting the change has been the awareness of the
      importance of the knowledge and skills required for the new role of laboratory
      professionals.

PMID- 11955485
TI  - The national health system: future possibilities for the clinical laboratory.
AB  - BACKGROUND: The heavy burden of the costs of medical care has brought changes in
      the public health policy. The changes are partly related to the health management
      factors, but several cultural, social and environmental factors have also had a
      significant impact on healthcare. The role of the laboratory is now considered
      amidst changes that have occurred in the American health model (free-trader) and
      in the European-Canadian model (universalistic). Moreover, costs and clinical
      decision-making in laboratories in Italy have also changed in response to the new
      focus on the pre- and post-analytical phases of the testing process. METHODS: In
      the present study, we used the Laboratory Information System (LIS) to evaluate
      whether the time involved in stages in the turnaround time (TAT) (admission,
      performance of tests, validation and decision-making for treatment) were reduced
      following improvements made to the laboratory organization and management of the
      pre-analytical and post-analytical phases. In particular, an analysis was made of
      laboratory testing for myocardial markers in patients with acute coronary
      syndrome. RESULTS: TAT for myocardial markers in an emergency setting was reduced
      by 30% following changes made in the laboratory organization and in the
      management of the pre-analytical and post-analytical phases of the testing
      process. CONCLUSIONS: Thanks to changes in healthcare service/system in Italy,
      laboratory services will now play a crucial role in cultural and socioeconomic
      changes, particularly where testing processes and techniques are concerned.

PMID- 11955486
TI  - Is there a future for clinical laboratories? Experience in the Marche Region,
      Italy.
AB  - The government of the Marche Region has approved an Act called the "Regional
      Health Plan" establishing rules for the organization and development of
      healthcare. The main aim of the general plan is to rationalize the activities of
      medical laboratories first by making up an inventory of existing facilities and
      tests performed, and by classifying laboratories on the basis of their
      specialization and the complexity of tests that they perform.Moreover, the
      possible role of point-of-care testing and the need for clinical advice by
      laboratory professionals has also been debated.

PMID- 11955487
TI  - Duties and responsibilities of laboratory scientists.
AB  - The duties and responsibilities of laboratory scientists are still evolving. In
      this paper, I briefly summarize some of the classical duties and responsibilities
      of Clinical Chemists in the areas of research, education and service.
      Furthermore, I developed some general rules of success for younger laboratorians.
      It is clear that we are living in exciting times and Clinical Chemists must learn
      to adapt very quickly to the continuing changes in our discipline. The new
      developments in science and technology suggest that we are yet to realize the
      best times of this exciting profession.

PMID- 11955488
TI  - Enhanced clinical consulting--moving toward the core competencies of laboratory
      professionals.
AB  - The large menu of laboratory assays available today makes it increasingly
      difficult for the non-specialist to order all necessary tests, avoid medical
      errors, and still contain cost. Curbside consultations, "intelligent" laboratory
      information systems, and medical information from the Internet cannot fully fill
      the need for expert advice on test selection and interpretation of laboratory
      results. In this communication, we show the need for a more active role for
      laboratory physicians to select and interpret tests, demonstrate that existing
      attempts to deal with this issue are insufficient, and describe the model system
      which we have instituted at our institution. We combine reflexive testing
      algorithms with narrative interpretations provided by medical laboratory
      professionals and thereby enable physicians to obtain relevant laboratory results
      and to arrive at a definitive diagnosis without having to order individual tests.
      In our experience, such an arrangement can significantly improve the quality of
      care and reduce the cost per case by decreasing the time to diagnosis, the number
      of tests ordered, and the number of patient visits. In addition, interpretations
      provide a new source of professional revenue for the expert laboratory physician.
      This leads to a new role for laboratory professionals, in which their expertise
      in the selection and interpretation of laboratory tests is fully utilized.

PMID- 11955489
TI  - The role, duties and responsibilities of technologists in the clinical
      laboratory.
AB  - Within the United Kingdom, the job functions of the technologist are carried out
      by Biomedical Scientists who account for the greater proportion of staff employed
      within clinical laboratories. Their traditional responsibilities have involved
      providing a quality service through their scientific, technical and clinical
      skills. During the 1990s, a number of factors combined, leading to a change in
      the way which quality was viewed within the National Health Service (NHS). This
      has changed the role of the technologist, encouraging them to broaden their
      knowledge and take on new skills and responsibility.

PMID- 11955490
TI  - Clinical governance--bridging management and clinical approaches to quality in
      the UK.
AB  - Clinical governance has, for the first time, placed the quality of healthcare as
      a direct responsibility of the Chief Executive and therefore the board of all NHS
      Trusts (Hospital), community providers and primary care trusts (general
      practitioners). The foundation for clinical governance was set out in the
      Department of Health Publication 'A first class service-quality in the new NHS'
      [Department Of Health, A First Class Service: Quality in the New NHS, London,
      HMSO, 1998]. Much of this had been precipitated by the Bristol cardiac surgery
      case and other series of medical disasters in the UK relating to cervical
      screening, breast screening, psychiatric care and pathological misdiagnoses. This
      new responsibility of clinical governance involves guaranteeing quality through a
      number of processes, many of which are currently in use and should be familiar to
      any clinician or manager. They include clinical effectiveness and optimisation of
      clinical care, clinical risk management, learning from complaints, professional
      development, good quality clinical data systems and involvement of patients and
      carers. This duty is equal to the other statutory responsibilities of NHS
      organisations, which are of financial probity, accountability and ensuring value
      for public money on behalf of the taxpayer.

PMID- 11955491
TI  - The EC4 register of European clinical chemists and EC4 activities.
AB  - The freedom of movement of people and goods within the European Union (EU) has a
      large impact for the member states. Particularly within health care it is
      important to recognize, or if necessary obtain, an adequate level of the quality
      of profession and practice, so that citizens know that health care is offered in
      their country at a level comparable to other countries. The importance of
      recognition also applies to laboratory medicine. European Communities
      Confederation of Clinical Chemistry (EC4) is the organization of societies for
      clinical chemistry and laboratory medicine in the EU. In Europe, health care
      develops in the direction where patients are treated in a health care chain
      environment. In this chain, patients move quickly from primary health institutes
      to secondary and tertiary institutes, and vice versa. This situation involves
      many health care workers including several laboratories. Diagnosis and therapy
      are now 'core business' of health care. Medical laboratories play an essential
      role in this. The broad spectrum of medical laboratory investigations make
      consultancy of medical laboratory specialists ever more important. The quality of
      both professionals and laboratories, as well as continuity of laboratory data
      within and between laboratories, are of utmost importance.EC4 is active in giving
      support to attain such quality. In most countries, this is the case at present.
      EC4 plays a central role in the Coordination of Automatic Recognition of
      Equivalence of Standards (CARE), if such a level exists or is achieved. Such CARE
      is focussed at three levels, the profession, quality of laboratories and
      calibration of laboratory data. The EC4 Register of European Clinical Chemists is
      open for colleagues educated in (bio)chemistry, pharmacy, biology as well as
      medicine, and trained according to the EC4 Syllabus. Equivalence of standards has
      been granted to national training schemes of 13 European Union countries. Since
      its opening in 1998, the number of applicants is growing steadily and quickly,
      reaching 1225 in May 2001.EC4 has published essential criteria for quality
      systems of medical laboratories, which formed the basis for a ISO draft
      international standard regarding quality and competence of medical
      laboratories.EC4 stimulates projects like the Calibration 2000 project in the
      Netherlands which focus on continuity of laboratory data, within-as well as
      between-laboratories.

PMID- 11955492
TI  - Educating a new generation of clinical laboratory scientists.
AB  - In many countries the new generation of laboratory scientists comes from the
      graduates of the biological sciences. Their training in the sciences is usually
      of high quality, but is almost totally lacking in the clinical application of
      their scientific knowledge. They obtain this clinical knowledge most often by on
      the-job training and experience. This paper describes a new undergraduate
      academic program in Laboratory Medicine developed at the Faculty of Medicine of
      the Technion, the Israel Institute of Technology. The program is carried out with
      the collaboration of the Faculty of Biology and the Faculty of Medicine, and upon
      completion of the classroom studies there is a period of internship for practical
      experience. The first students of the program are now in their internship period
      and will graduate this year.

PMID- 11955493
TI  - The Italian way to Continuing Education in Medicine.
AB  - BACKGROUND: Continuing education is a right and a duty for all professionals
      working in the healthcare system, and the Ministry of Health, has recently
      developed and introduced an experimental program for Continuing Education in
      Medicine (ECM) throughout Italy. METHODS: The guiding principles and values of
      ECM are to assure the quality of educational events and to ensure that
      professionals can choose from among several opportunities for gaining credits.
      Although promoted by regional healthcare authorities, the educational program
      must be homogeneous throughout the national territory. RESULTS: Over the last few
      months, the National Commission for ECM has defined the role and responsibilities
      of different organisms and authorities involved in the ECM program. Each
      professional is expected to gain a total score of at least 150 credits over a 5
      year timespan. Moreover, the Commission has established criteria for the
      accreditation of educational initiatives, the verification of their quality, and
      the evaluation of the educational benefit participants have from them.
      CONCLUSIONS: The ECM program in Italy is here to stay. It provides professionals
      with the opportunity to improve the quality of their knowledge, competence, and
      skills. Medical associations can now reevaluate their role and commitment to
      improving the quality of healthcare by providing all professionals with a better
      education and qualifications.

PMID- 11955494
TI  - Continuing medical education: a challenge to the Italian Scientific Societies of
      Laboratory Medicine.
AB  - BACKGROUND: In the modern health service, it is no longer acceptable for any
      clinician or other professional to abstain from continuing education after
      qualification. This is particularly true in the field of laboratory medicine
      because of the dramatic changes that have occurred in the organization, number
      and types of tests, and role of medical laboratories. In Italy, a program for
      continuing education in medicine (Educazione Continua in Medicina (ECM)) has
      recently been promoted by the National Government. METHODS: Continuing education
      (CE) in laboratory medicine should include all educational activities that are
      pertinent to a person's professional skills, activities, interests, and growth.
      Continuing education can take many forms. In particular, a variety of programs
      are available that enable employees to improve their knowledge and skills while
      reducing their travel and absence from the laboratory. RESULTS: The present paper
      describes the recent redefinition of the mission, aims and structure of the
      Scientific Division of the Italian Society of Clinical Biochemistry and Clinical
      Molecular Biology (SIBioC) and the role it plays in making available to all
      associates a program for continuing education in the field of Laboratory
      Medicine. CONCLUSIONS: The activation of a national program for continuing
      education in medicine (ECM) in Italy provides a great opportunity for all
      professionals of the healthcare sector and for laboratorians, in particular. This
      educational project offers an unrivalled opportunity for the Italian Scientific
      Societies of Laboratory Medicine to weave quality improvement into their
      relationships with associates, thus reappraising their missions and goals.

PMID- 11955495
TI  - Fetlock joint kinematics differ with age in Thoroughbred [was thoroughbred]
      racehorses.
AB  - Fetlock joint kinematics during galloping in 2-, 3-, 4-, and 5-year-old
      Thoroughbreds in race training were quantified to determine if differences due to
      age could account for the observation that 2-year old Thoroughbred racehorses
      incur a high number of injuries to the bones and soft tissues in the distal
      forelimbs during training and at the outset of racing. Twelve Thoroughbred
      racehorses were videotaped in the sagittal plane at 250 frames/s during their
      daily galloping workout on a 7/8 mile sand-surface training track. Four galloping
      strides were recorded for each horse and subsequently digitized to determine
      fetlock joint angles of the leading forelimb during the limb support period of a
      stride. Four kinematic variables were measured from each stride's angular
      profile: angle of fetlock joint dorsi-flexion at mid-stance, negative angular
      velocity, positive angular velocity and time from hoof impact to mid-stance phase
      of limb support. The 2-year old Thoroughbreds had significantly quicker rates of
      dorsi-flexion of their fetlock joints than 3- (p=0.01), 4- (p=0.01), and 5-year
      old (p<0.01) Thoroughbreds following impact of the leading forelimb during
      moderate galloping (avg. 14 m/s). Higher rates of dorsi-flexion in young
      Thoroughbreds may reflect immaturity (lack of stiffness) of the suspensory
      apparatus tissues.

PMID- 11955496
TI  - A simple and inexpensive system for monitoring jaw movements in ambulatory
      humans.
AB  - A simple and inexpensive method for recording vertical movements of the human
      mandible relative to the maxilla is presented. Measurements are made from
      accelerometers and a Hall-effect device temporarily glued to the upper and lower
      anterior teeth. The accelerometer signals are integrated once to give velocity
      and a second time to give position. Movements of the mandible relative to the
      maxilla are obtained by integrating the difference between the two accelerometer
      signals. The (relative) velocity and position records derived in this way are
      linear, but subject to drift when the jaw is stationary. Steady mandibular
      position is obtained from the Hall-effect system, but this signal must be
      corrected for its inherent non-linearity. This device can record rapid movements
      of the mandible even when the head is unrestrained, and interferes minimally with
      normal jaw movements.

PMID- 11955497
TI  - A cell-culture system for long-term maintenance of elevated hydrostatic pressure
      with the option of additional tension.
AB  - In cell stress research, there is still a need to apply long-term hydrostatic
      pressure without changing any other environmental condition. We present here a
      new, open, pressurized chamber system allowing long-term sustained and dynamic
      application of hydrostatic pressure with the option of additional tension. Based
      on the computer-controlled Flexcell Strain Unit, we designed a pressurized
      chamber with a dynamic airflow and a defined membrane extension, which can be
      regulated by spacers. During operation up to 26.6kPa, O(2) partial pressures and
      pH in the cell-culture medium do not change compared to control cultures kept at
      normal atmosphere.

PMID- 11955498
TI  - Postural control during lifting.
AB  - Any voluntary motion of the body causes an internal perturbation of balance. Load
      transfer during manual material handling may increase these perturbations. This
      study investigates effects of stance condition on postural control during
      lifting. Nineteen healthy subjects repeatedly lifted and lowered a load between a
      desk and a shelf. The base of support was varied between parallel and step
      stance. Ground reaction force and segmental kinematics were measured. Load
      transfer during lifting perturbed balance. In parallel stance postural response
      consisted of axial movements in the sagittal plane. Such strategy was accompanied
      by increased posterior shear forces after lift-off. Lifting in step stance
      provided extended support in anterior/posterior direction. The postural control
      mechanisms in the sagittal plane are less complex as compared to parallel stance.
      However, lifting in step stance was asymmetrical and thus accompanied by distinct
      lateral transfer of the body. Lateral shear forces were larger as compared to
      parallel stance. Both lifting techniques exhibit positive and negative aspects.
      We cannot recommend either one as being better in terms of postural control.

PMID- 11955499
TI  - Flow on the symmetry plane of a total cavo-pulmonary connection.
AB  - The flow inside a total cavo-pulmonary connection, a bypass operation of the
      right heart adopted in the presence of congenital malformation, is here studied
      for a specific geometry which has been recently introduced in clinics. The
      analysis has been performed by preliminary experimental observation and a novel
      Navier-Stokes formulation on the symmetry plane. This method, once some basic
      hypotheses are verified, allows to reproduce the flow on the symmetry plane of a
      three-dimensional field by using an extension of the two-dimensional approach.
      The analysis has confirmed the existence of a central vortex showing that it is
      not a real vortex (i.e. a place with accumulation of vorticity) but, rather, a
      weakly dissipative recirculating zone. It is surrounded by a shear layer that
      becomes spontaneously unsteady at moderately high Reynolds number. The
      topological changes and energy dissipation have been analysed in both cases of
      unbalanced and of balanced pulmonary artery and caval flows.

PMID- 11955500
TI  - An EMG-based, muscle driven forward simulation of single support phase of gait.
AB  - This paper describes the process used to generate lower limb kinematics during
      single limb stance phase of gait, using musculoskeletal modelling, muscle driven
      forward simulation and gradient based optimisation techniques (including design
      of experiment techniques). Initial inputs to the forward simulation process were
      the normalised quantified muscle activation patterns of 22 muscles, and the
      initial segmental configuration (both angles and angular velocity) derived from
      Winter (The biomechanics and motor control of human gait, 1987, University of
      Waterloo Press, pp. 1-72). Two distinct musculoskeletal models (one including 6
      DOF, the other 7 DOF) were defined and a muscle driven forward simulation was
      implemented.A series of optimisation sequences then were executed to modify the
      muscle activation patterns and initial segmental configuration, until the system
      output of the forward simulation approximated the angle data reported by. The
      accuracy and effectiveness of the analysis sequence proposed and the model
      response obtained using two distinct musculoskeletal models were verified and
      analysed with respect to the kinesiology of normal walking.

PMID- 11955502
TI  - Stress analysis of the standing foot following surgical plantar fascia release.
AB  - Plantar fascia release is a surgical alternative for patients who suffer chronic
      heel pain due to plantar fasciitis and are unaffected by conservative treatment.
      A computational (finite element) model for analysis of the structural behavior of
      the human foot during standing was utilized to investigate the biomechanical
      effects of releasing the plantar fascia. The model integrates a system of five
      planar structures in the directions of the foot rays. It was built according to
      accurate geometric data of MRI, and includes linear and non-linear elements that
      represent bony, cartilaginous, ligamentous and fatty tissues. The model was
      successfully validated by comparing its resultant ground reactions with foot
      ground pressure measurements and its predicted displacements with those observed
      in radiological tests. Simulation of plantar fascia release (partial or total)
      was accomplished by gradually removing parts of the fascia in the model. The
      results showed that total fascia release causes extensive arch deformation during
      standing, which is greater than normal deformation by more than 2.5mm. Tension
      stresses carried by the long plantar ligaments increased significantly, and may
      exceed the normal average stress by more than 200%. Since the contribution of the
      plantar fascia to the foot's load-bearing ability is of major importance, its
      release must be very carefully considered, and the present model may be used to
      help surgeons decide upon the desired degree of release.

PMID- 11955501
TI  - Effects of fatigue and load variation on metatarsal deformation measured in vivo
      during barefoot walking.
AB  - This in vivo study presents information to assist in the understanding of
      metatarsal stress fracture etiology. The aims were (a) to provide a fundamental
      description of loading patterns of the second metatarsal (MTII) during barefoot
      walking, and (b) to investigate the hypothesis that MTII dorsal strain increases
      with fatigue and external carrying load. Dorsal MTII strain was measured in vivo
      under local anaesthetic with an instrumented staple in eight subjects.
      Experimental conditions were external loading with a 20 kg backpack and pre- and
      post-fatigue. M. flexor digitorum longus electromyography tentatively indicated
      fatigue after an extended walking treatment. A reproducible, cyclic temporal
      pattern of dorsal MTII surface deformation was described. Mean peak compression
      and tension strains in unloaded barefoot walking were -1534 +/- 636 and 363 +/-
      359 muepsilon, respectively. Mean peak compression strain rate (SR) was -4165 +/-
      1233 muepsilon/s. Compression strain increased significantly (alpha=0.05) both
      with the addition of the backpack and post-fatigue while maximum tension
      decreased significantly post-fatigue. SR increased significantly with the
      addition of the backpack. The highest plantar force time integrals were recorded
      underneath the heads of metatarsals II-V for all conditions (1561Ns pre-fatigue,
      without backpack; 2123Ns post, with). EMG and plantar pressure data presented a
      comprehensive description of biomechanical parameters influencing dorsal MTII
      deformation and alterations in strain following two experimental conditions were
      suggested as contributing factors in the pathogenesis of metatarsal stress
      fractures.

PMID- 11955503
TI  - A model analysis of internal loads, energetics, and effects of wobbling mass
      during the whole-body vibration.
AB  - The internal loads, energetics, and the effects of wobbling mass during the whole
      body vibration are studied in terms of analysis and comparison of two models: one
      is a system of four degrees-of-freedom with rigid and wobbling masses in both
      lower body and upper body (Model A), while the other one (Model B) is a system of
      three degrees-of-freedom with a rigid upper body and is otherwise identical to
      Model A. The main findings are the following: (1) The wobbling mass in the upper
      body is able to reduce the total internal load on the rigid mass of the upper
      body considerably. (2) "Partial" internal loads on a certain part of the body may
      be even larger than the total load on the same part of the body because of the
      phase differences among the partial loads. Therefore, a full consideration of
      safety during the whole-body vibration has to take not only the total, but also
      all the partial internal loads into account. (3) The fluctuation of power input
      and the fluctuation of mechanical energy could be much larger than the
      fluctuation of dissipation rate. (4) For frequencies higher than the resonance
      frequency range, the amplitude of the oscillation of the centre of mass of the
      body is so reduced that only the change of elastic potential energy dominates in
      the change of mechanical energy. Thus, a simple picture of energy flow is
      obtained as follows: for approximately one half of the oscillation period, the
      energy flows from the vibrator into the human body and is mainly stored in the
      muscle-tendon system, while for the remaining approximate half of the period, the
      energy flows from the muscle-tendon system back to the vibrator with a slightly
      smaller amount because a small part of the flown-in energy has been dissipated.

PMID- 11955504
TI  - A movement criterion for running.
AB  - The adjustment of the leg during running was addressed using a spring-mass model
      with a fixed landing angle of attack. The objective was to obtain periodic
      movement patterns. Spring-like running was monitored by a one-dimensional stride
      to-stride mapping of the apex height to identify mechanically stable fixed
      points. We found that for certain angles of attack, the system becomes self
      stabilized if the leg stiffness was properly adjusted and a minimum running speed
      was exceeded. At a given speed, running techniques fulfilling a stable movement
      pattern are characterized by an almost constant maximum leg force. With
      increasing speed, the leg adjustment becomes less critical. The techniques
      predicted for stable running are in agreement with experimental studies.
      Mechanically self-stabilized running requires a spring-like leg operation, a
      minimum running speed and a proper adjustment of leg stiffness and angle of
      attack. These conditions can be considered as a movement criterion for running.

PMID- 11955505
TI  - Skeletal muscle is sensitive to the tension-time integral but not to the rate of
      change of tension, as assessed by mechanically induced signaling.
AB  - Mechanical forces regulate many cellular processes. Mechanotransduction, however,
      is poorly understood. In skeletal muscle, mechanical forces have a major impact
      on the regulation of cellular volume, yet the nature of the mechanical
      stimulation to which muscle is most sensitive is unknown. It was recently
      demonstrated that activation of the mechanically-sensitive kinase p54 jun-N
      terminal-kinase (JNK), is a quantitative marker of mechanical stimulation in
      skeletal muscle. This marker was shown to be more sensitive to peak tension than
      to other tension-related parameters such as the tension-time integral (TTI) and
      the rate of change of tension (dT/dt). The purpose of the present study was to
      parcel out the contribution of TTI and dT/dt to mechanical stimulation of muscle
      under conditions of constant peak tension. The rat medial gastrocnemius in situ
      was subjected to one of four 5-min passive stretch protocols consisting of equal
      length excursions, but differing in displacement-time integral (4%, 40%, or 100%)
      and/or rate of stretch (0, 3, or 30 mm/s), and the resulting p54-JNK
      phosphorylation was assessed. A linear relationship between TTI and p54-JNK
      signaling was observed. However, no effect of dT/dt was observed. It is concluded
      that peak tension and TTI are necessary parameters for modeling the mechanical
      stimulus-response of muscle. Additionally, the mechanism of mechanotransduction
      is sensitive to peak tension and TTI, but not to dT/dt, and thus exhibits spring
      like behavior. These findings may contribute to the refinement of disuse atrophy
      countermeasures.

PMID- 11955506
TI  - Fluid dynamics of the left ventricular filling in dilated cardiomyopathy.
AB  - Modifications in diastolic function occur in a broad range of cardiovascular
      diseases and there is an increasing evidence that abnormalities in left
      ventricular function may contribute significantly to the symptomatology. The flow
      inside the left ventricle during the diastole is here investigated by numerical
      solution of the Navier-Stokes equations under the axisymmetric assumption. The
      equation are written in a body-fitted, moving prolate spheroid, system of
      coordinates and solved using a fractional step method. The system is forced by a
      given volume time-law derived from clinical data, and varying the two-degrees-of
      freedom ventricle geometry on the basis of a simple model. The solution under
      healthy conditions is analysed in terms of vorticity dynamics, showing that the
      flow field is characterised by the presence of a vortex wake; it is attached to
      the mitral valve during the accelerating phase of the E-wave, and it detaches and
      translate towards the ventricle apex afterwards. The flow evolution is discussed,
      results are also reported as an M-mode representation of colour-coded Doppler
      velocity maps. In the presence of ventricle dilatation the mitral jet extends
      farther inside the ventricle, propagation velocity decreases, and the fluid
      stagnates longer at the apex.

PMID- 11955507
TI  - Computer simulations of mitosis and interdependencies between mitosis
      orientation, cell shape and epithelia reshaping.
AB  - Finite element-based computer simulations are used to investigate mitosis and how
      mitosis, cell shape, and epithelium reshaping depend on each other. Frame- and
      cell-oriented patterns of mitosis with growing and non-growing daughter cells are
      considered. Previous simulations have shown that applied stresses or strains can
      reshape cells so that their long axes are aligned in the principal stretch
      direction. The simulations reported here show that this can produce global
      alignment of the mitosis cleavage planes. Other simulations reported here show
      that mitoses with suitably aligned cleavage planes can drive epithelium
      reshaping. Formulas that quantify these and other dependencies are derived. These
      formulas provide quantitative relationships against which current hypotheses
      regarding epithelia reshaping in real biological systems can be evaluated.

PMID- 11955508
TI  - Theoretical and experimental aspects of erythrocyte filterability testing; flow
      acceleration and systemic resistance.
AB  - Blood cell filterability is an established method in blood rheology. The dynamics
      at flow onset and its relevance to the data interpretation is, however, not fully
      known. This paper aims to investigate what controls the length and slope of flow
      acceleration as the medium accelerates to reach the steady state, and how this
      phenomenon may interfere with the data output. The acceleration time was not
      constant. With buffer the steady-state flow showed a logarithmic correlation
      (p<0.05) versus acceleration time and a linear correlation (p<0.001) versus
      acceleration slope. With 5% erythrocyte resuspension the steady-state flow
      instead demonstrated a linear relationship versus acceleration time (p<0.001) and
      no correlation versus acceleration slope. A cut-off timing of 0.6s is suggested
      to avoid artifacts associated with flow acceleration. The possible influence on
      data interpretation from the flow channel systemic resistance was also addressed,
      and found to significantly underestimate measurable changes in erythrocyte
      properties from unprocessed flow curves. This was despite the traditional
      correction for blank filtration flow. Both acceleration and effects from systemic
      resistance do probably have minor influence on the historic data interpretation
      but could perhaps be considered in the methodology to sharpen the data output.

PMID- 11955509
TI  - Spatio-temporal parameters of gait measured by an ambulatory system using
      miniature gyroscopes.
AB  - In this study we describe an ambulatory system for estimation of spatio-temporal
      parameters during long periods of walking. This original method based on wavelet
      analysis is proposed to compute the values of temporal gait parameters from the
      angular velocity of lower limbs. Based on a mechanical model, the medio-lateral
      rotation of the lower limbs during stance and swing, the stride length and
      velocity are estimated by integration of the angular velocity. Measurement's
      accuracy was assessed using as a criterion standard the information provided by
      foot pressure sensors. To assess the accuracy of the method on a broad range of
      performance for each gait parameter, we gathered data from young and elderly
      subjects. No significant error was observed for toe-off detection, while a slight
      systematic delay (10 ms on average) existed between heelstrike obtained from
      gyroscopes and footswitch. There was no significant difference between actual
      spatial parameters (stride length and velocity) and their estimated values.
      Errors for velocity and stride length estimations were 0.06 m/s and 0.07 m,
      respectively. This system is light, portable, inexpensive and does not provoke
      any discomfort to subjects. It can be carried for long periods of time, thus
      providing new longitudinal information such as stride-to-stride variability of
      gait. Several clinical applications can be proposed such as outcome evaluation
      after total knee or hip replacement, external prosthesis adjustment for amputees,
      monitoring of rehabilitation progress, gait analysis in neurological diseases,
      and fall risk estimation in elderly.

PMID- 11955510
TI  - Compliance calibration for fracture testing of equine cortical bone.
AB  - An experimental compliance calibration method for measuring crack length in
      fracture toughness tests of cortical bone was developed. Calibration tests were
      conducted on twenty compact type fracture specimens machined from the mid
      diaphysis of five pairs of equine third metacarpal bones. Specimens were oriented
      for crack propagation in a direction transverse to the longitudinal axis of the
      bone. Specimen compliance was determined from the load vs. crack opening
      displacement record over a range of crack lengths from 0.48 to 0.75 times the
      specimen width. The results demonstrate that the compliance calibration method
      developed for isotropic materials can be used to determine crack length in bone,
      which is transversely isotropic. However, specimens from lateral and dorsal
      regions exhibited significantly different compliance calibrations even after
      differences in elastic modulus were taken into account in the normalized
      compliance.

PMID- 11955511
TI  - Body segment inertial parameter estimation for the general population of older
      adults.
AB  - The practical determination of accurate body segment inertial parameters for the
      general older adult population remains a problem, especially in estimating these
      parameters for women and accounting for variations in body type. A method is
      presented for determining the mass and center of mass location of the body
      segments of individuals within the general population of older adults. Effects of
      sex and body type on older adult mass distribution are accounted for using 32
      easily obtainable body measurements. The method is based on existing results from
      different data sources and employs a combination of validated estimation
      approaches, including: body mass and segment length proportions, linear and
      nonlinear regression equations, and a mathematical model of the trunk. The method
      was applied to a validation sample of healthy, community-dwelling older adults
      (29 men, 50 women). Predicted body mass was 96.7+/-4.8% and 95.7+/-3.7% of
      measured body mass in the men and women, respectively. The estimates of body
      segment mass and trunk center of mass location for the sample population
      approximate those reported in the literature, supporting the validity of the
      described method. By producing practical, subject-specific estimates of body
      segment inertial parameters, the method should allow more accurate biomechanical
      analyses of the older adult population.

PMID- 11955512
TI  - Analysis of a swimmer's hand and arm in steady flow conditions using
      computational fluid dynamics.
AB  - Propulsive forces generated by swimmers' hands and arms have, to date, been
      determined strictly through experimental testing. As an alternative to these
      complex and costly experiments, the present research has applied the numerical
      technique of computational fluid dynamics (CFD) to calculate the steady flow
      around a swimmer's hand and arm at various angles of attack. Force coefficients
      computed for the hand and arm compared well with steady-state coefficients
      determined experimentally. The simulations showed significant boundary layer
      separation from the arm and hand, suggesting that Bernoulli's equation should not
      be used to mathematically describe the lift generated by a swimmer. Additionally,
      "2D" lift was shown to be inaccurate for the arm at all angles of attack and for
      the hand near angles of attack of 90 degrees. Such simulations serve to validate
      the chosen CFD techniques, and are an important first step towards the use of CFD
      methods for determining swimming hydrodynamic forces in more complex unsteady
      flow conditions.

PMID- 11955513
TI  - Comment on: Hip contact forces and gait patterns from routine activities.

PMID- 11955515
TI  - Identification of a new site in the S1 ligand binding region of the NMDA receptor
      NR2A subunit involved in receptor activation by glutamate.
AB  - Activation of N-methyl-d-aspartate (NMDA) receptors requires the binding of both
      glutamate and glycine to independent sites on the receptor. These ligands bind to
      NR2 and NR1 subunits respectively. Ligand binding residues are located in two non
      contiguous domains, S1 and S2, which have been implicated in glutamate binding in
      other ionotropic glutamate receptor subunits. To further define the amino acids
      through which glutamate activates the receptor, we generated single-site
      mutations to the NR2A subunit, and expressed them with wild type NR1 in HEK 293
      cells. Using calcium imaging and whole cell patch clamp we determined glutamate
      and glycine potencies. Of the eight residues mutated we identified five (E413,
      K484, A508, G685 and G688), whose mutation leads to a large reduction (from 4- to
      1000-fold) in glutamate potency, consistent with a role for these residues in
      receptor activation by glutamate. The potency of glycine was largely unchanged by
      these mutations. Thus our results extend the knowledge base of residues involved
      in NMDA receptor function and identifies a new site in S1, in the region of A508,
      that has a role in receptor activation by glutamate.

PMID- 11955516
TI  - Decrease in calbindin content significantly alters LTP but not NMDA receptor and
      calcium channel properties.
AB  - The contribution of the cytosolic calcium binding protein calbindin D(28K) (CaBP)
      to the synaptic plasticity was investigated in hippocampal CA1 area of wild-type
      and antisense transgenic CaBP-deficient mice. We showed that long-term
      potentiation (LTP) induced by tetanic stimulation in CaBP-deficient mice was
      impaired. The fundamental biophysical properties of NMDA receptors and their
      number were not modified in CaBP-deficient mice. We also demonstrated that the
      physiological properties of calcium channels were identical between genotypes. An
      insufficient Ca(2+) entry through NMDA receptors or calcium channels, or a
      decrease in NMDA receptor density are unlikely to explain this impairment of LTP.
      Interestingly, we showed that the loss of LTP was not prevented by glycine but
      was restored in the presence of a low concentration of the NMDA receptor
      antagonist D-APV (5 microM) and of the calcium chelator BAPTA-AM (5 microM).
      Moreover, we observed a loss of LTP in the wild-type mice when the postsynaptic
      tetanic-induced [Ca(2+)](i) rise is excessively increased. Conversely, a weaker
      tetanus stimulation allowed LTP induction and maintenance in CaBP-deficient mice.
      These results suggest that a higher cytosol [Ca(2+)](i), due to the decrease of
      CaBP expression may impair LTP induction and maintenance mechanisms without
      affecting the mechanisms of calcium entry. Thus, CaBP plays a critical role in
      long term synaptic plasticity by limiting the elevation of calcium rise in the
      cytosol to some appropriate spatio-temporal pattern.

PMID- 11955517
TI  - Neuronal hyperexcitability induced by repeated brief episodes of hypoxia in rat
      hippocampal slices: involvement of ionotropic glutamate receptors and L-type
      Ca(2+) channels.
AB  - Repeated exposures of rat hippocampal slices to short episodes of hypoxia induce
      a sustained decrease in the threshold of the development of stimulus-evoked
      epileptiform discharges in CA1 pyramidal neurons. We have previously demonstrated
      that the K(+)(o)-induced hyperexcitability required functional L-type voltage
      dependent Ca(2+) channels and NMDA-receptors, but was independent of AMPA/kainate
      receptor activation. As hypoxia/ischaemia can lead to increased K(+)(o), the
      epileptiform activity observed after exposure to these challenges could also
      result from high K(+)(o). The purpose of this study was: (i) to determine whether
      ionotropic glutamate receptors and L-type Ca(2+) channels are involved in the
      development of epileptiform activity induced by repeated exposures of hippocampal
      slices to hypoxia; and (ii) to compare the properties of hypoxia- and high
      K(+)(o)-induced hyperexcitability. Population spike of presynaptic fibres with
      field excitatory postsynaptic potential from the stratum radiatum, and population
      spike of CA1 pyramidal neurons from the stratum pyramidale, were recorded
      simultaneously in the CA1 area of rat hippocampal slices in response to
      electrical stimulation of the Schaffer collateral/commissural fibres. Repeated,
      brief hypoxic episodes induced a sustained decrease in the threshold for
      development of evoked epileptiform discharges that was associated with long-term
      potentiation of the CA3-CA1 synapses, but without EPSP-spike potentiation (i.e.
      in contrast to high K(+)(o)-induced hyperexcitability). The selective antagonist
      of NMDA receptors, D-APV (25 microM), and the selective blocker of L-type Ca(2+)
      channels, nifedipine (10 microM) depressed the development of hypoxia-induced
      hyperexcitability. However, in contrast to high K(+)(o)-induced
      hyperexcitability, hypoxia-induced hyperexcitability was also blocked by the
      AMPA/kainite-receptor antagonist, CNQX (5 microM). The present findings confirm
      that repeated, brief episodes of hypoxia, like exposure to high extracellular
      K(+), can induce a pro-epileptic state in the CA1 neuronal network, but that the
      mechanisms leading to hyperexcitability are different for the two stimuli.

PMID- 11955518
TI  - L-type Ca2+ channel modulation by dihydropyridines potentiates kappa-opioid
      receptor agonist induced acute analgesia and inhibits development of tolerance in
      rats.
AB  - The effect of 1,4-dihydropyridine (DHP) calcium channel blockers (CCBs),
      nimodipine (NIM) and lercanidipine (LDP) on the analgesic response of selective
      kappa-opioid receptor agonists, U50,488H, PD117,302 and U69,593 was determined in
      male Sprague-Dawley rats using the tail-flick test. The effect of NIM on
      development of tolerance to U50,488H-induced analgesia and the status of brain
      DHP-sensitive Ca(2+) channel (L-type) binding sites in both U50,488H-naive and
      tolerant rats was determined using the highly selective DHP radioligand,
      [(3)H]PN200-110. Tolerance was induced by injecting U50,488H (25 mg/kg, i.p.)
      twice daily for 4 days. Intraperitoneal (i.p.) injection of kappa-opioid receptor
      agonists produced a dose-dependent acute analgesic response. NIM (1 mg/kg; i.p.)
      and LDP (0.3 mg/kg; i.p.) used in the study produced no tail-flick analgesia.
      Administration of NIM and LDP (15 min prior) significantly potentiated the
      analgesia produced by three kappa-opioid receptor agonists. Tolerance developed
      completely to the analgesic effect induced by U50,488H (25 mg/kg, i.p.)
      administered on the 5th day. NIM (1 mg/kg, i.p.) twice daily for 4 days not only
      completely inhibited the development of tolerance to analgesic response but also
      significantly potentiated it (supersensitivity). There was a significant up
      regulation of DHP binding sites (B(max): +41%) in whole brain membranes of
      tolerant rats when compared to vehicle treated naive rats, implicating increased
      influx of Ca(2+) through L-type channels in kappa-opioid tolerance. U50,488H (25
      mg/kg, i.p.) and NIM (1 mg/kg, i.p.) twice daily for 4 days also resulted in an
      equivalent up-regulation of DHP binding sites (+36%) as that of U50,488H alone.
      These results strongly suggest a functional role of L-type Ca(2+) channels in the
      regulation of pain sensitivity, mechanism of kappa-opioid analgesia and
      expression of tolerance.

PMID- 11955519
TI  - Interaction between P2Y and NMDA receptors in layer V pyramidal neurons of the
      rat prefrontal cortex.
AB  - In the first part of this study, monosynaptic excitatory postsynaptic potentials
      (EPSPs) in layer V of the rat prefrontal cortex were evoked by electrical
      stimulation of layer I. Recordings by intracellular sharp microelectrodes showed
      that EPSPs were concentration-dependently facilitated by the P2 receptor
      antagonistic ATP analogue 2-methylthio ATP (2-MeSATP), while ATP itself depressed
      the synaptic potentials. The inhibitory effect of ATP turned into facilitation in
      the presence of the adenosine A(1) receptor antagonist DPCPX. The 2-MeSATP
      induced potentiation of EPSP amplitudes were prevented by the P2 receptor
      antagonists PPADS and Suramin. The EPSP was almost abolished by coapplication of
      the NMDA receptor antagonist AP-5 and the AMPA/kainate receptor antagonist CNQX.
      After blockade of the NMDA receptor-mediated part of the EPSP by AP-5, the
      stimulatory effect of 2-MeSATP disappeared. When NMDA or AMPA were pressure
      applied onto pyramidal cells, only the NMDA-induced depolarization was
      potentiated by 2-MeSATP. In the second part of the study, NMDA-induced currents
      were measured by whole-cell patch-clamp pipettes. ATP, 2-MeSATP, UDP and UTP
      potentiated the response to NMDA, while ADP-beta-S was inactive. PPADS
      antagonized the effect of ATP. Synaptic isolation of pyramidal neurons by a
      Ca(2+)-free medium or tetrodotoxin did not alter the effect of ATP which,
      however, was markedly depressed when GTP in the micropipette was replaced by GDP
      beta-S. These observations suggest that in layer V pyramidal neurons of the
      prefrontal cortex postsynaptically localized P2Y receptors interact with NMDA
      receptor-channels.

PMID- 11955520
TI  - P2 receptor modulation and cytotoxic function in cultured CNS neurons.
AB  - In this study we investigate the presence, modulation and biological function of
      P2 receptors and extracellular ATP in cultured cerebellar granule neurons. As we
      demonstrate by RT-PCR and western blotting, both P2X and P2Y receptor subtypes
      are expressed and furthermore regulated as a function of neuronal maturation. In
      early primary cultures, mRNA for most of the P2 receptor subtypes, except P2X(6),
      are found, while in older cultures only P2X(3), P2Y(1) and P2Y(6) mRNA persist.
      In contrast, P2 receptor proteins are more prominent in mature neurons, with the
      exception of P2Y(1). We also report that extracellular ATP acts as a cell death
      mediator for fully differentiated and mature granule neurons, for dissociated
      striatal primary cells and hippocampal organotypic cultures, inducing both
      apoptotic and necrotic features of degeneration. ATP causes cell death with
      EC(50) in the 20-50 microM range within few minutes of exposure and with a time
      lapse of at most two hours. Additional agonists for P2 receptors induce toxic
      effects, whereas selected antagonists are protective. Cellular swelling, lactic
      dehydrogenase release and nuclei fragmentation are among the features of ATP
      evoked cell death, which also include direct P2 receptor modulation. Comparably
      to P2 receptor antagonists previously shown preventing glutamate-toxicity, here
      we report that competitive and non-competitive NMDA receptor antagonists inhibit
      the detrimental consequences of extracellular ATP. Due to the massive
      extracellular release of purine nucleotides and nucleosides often occurring
      during a toxic insult, our data indicate that extracellular ATP can now be
      included among the potential causes of CNS neurodegenerative events.

PMID- 11955521
TI  - Mutation of the GABAA receptor M1 transmembrane proline increases GABA affinity
      and reduces barbiturate enhancement.
AB  - All GABA(A) receptor (GABAR) subunits include an invariant proline in a consensus
      motif in the first transmembrane segment (M1). In receptors containing bovine
      alpha1, beta1 and gamma2 subunits, we analyzed the effect of mutating this M1
      proline to alanine in the alpha1 or beta1 subunit using 3 different expression
      systems. The beta1 subunit mutant, beta1(P228A), reduced the EC(50) for GABA
      about 10-fold in whole cell recordings in HEK293 cells and L929 fibroblasts. The
      corresponding alpha1 subunit mutant (alpha1(P233A)) also reduced the GABA EC(50)
      when expressed in Xenopus oocytes; alpha1(P233A)beta1gamma2S receptors failed to
      assemble in HEK293 cells. Binding of [(3)H]flumazenil and [(3)H]muscimol to
      transfected HEK293 cell membranes showed similar levels of receptor expression
      with GABARs containing beta1 or beta1(P228A) subunits and no change in the
      affinity for [(3)H]flumazenil; however, the affinity for [(3)H]muscimol was
      increased 6-fold in GABARs containing beta1(P228A) subunits. In L929 cells,
      presence of the beta1(P228A) subunit reduced enhancement by barbiturates without
      affecting enhancement by diazepam or alfaxalone. Single channel recordings from
      alpha1beta1gamma2S and alpha1beta1(P228A)gamma2L GABARs showed similar channel
      kinetics, but beta-mutant containing receptors opened at lower GABA
      concentrations. We conclude that the beta1 subunit M1 segment proline affects the
      linkage between GABA binding and channel gating and is critical for barbiturate
      enhancement. Mutation of the M1 proline in the alpha1 subunit also inhibited
      receptor assembly.

PMID- 11955522
TI  - Lamotrigine reduces spontaneous and evoked GABAA receptor-mediated synaptic
      transmission in the basolateral amygdala: implications for its effects in seizure
      and affective disorders.
AB  - Lamotrigine (LTG) is an antiepileptic drug that is also effective in the
      treatment of certain psychiatric disorders. Its anticonvulsant action has been
      attributed to its ability to block voltage-gated Na(+) channels and reduce
      glutamate release. LTG also affects GABA-mediated synaptic transmission, but
      there are conflicting reports as to whether inhibitory transmission is enhanced
      or suppressed by LTG. We examined the effects of LTG on GABA(A) receptor-mediated
      synaptic transmission in slices from rat amygdala, a brain area that is
      particularly important in epileptogenesis and affective disorders. In
      intracellular recordings, LTG (100 microM) reduced GABA(A) receptor-mediated
      IPSPs evoked by electrical stimulation in neurons of the basolateral nucleus. In
      whole-cell recordings, LTG (10, 50 and 100 microM) decreased the frequency and
      amplitude of spontaneous IPSCs, as well as the amplitude of evoked IPSCs, but had
      no effect on the kinetics of these currents. LTG also had no effects on the
      frequency, amplitude or kinetics of miniature IPSCs recorded in the presence of
      TTX. These results suggest that in the basolateral amygdala, LTG suppresses
      GABA(A) receptor-mediated synaptic transmission by a direct and/or indirect
      effect on presynaptic Ca(++) influx. The modulation of inhibitory synaptic
      transmission may be an important mechanism underlying the psychotropic effects of
      LTG.

PMID- 11955523
TI  - The role of nicotinic receptor beta-2 subunits in nicotine discrimination and
      conditioned taste aversion.
AB  - The subtypes of nicotinic receptors at which the behavioural effects of nicotine
      originate are not fully understood. These experiments use mice lacking the beta2
      subunit of nicotinic receptors to investigate its role in nicotine discrimination
      and conditioned taste aversion (CTA). Wild-type and mutant mice were trained
      either in a two-lever nicotine discrimination procedure using a tandem schedule
      of food reinforcement, or in a counterbalanced two-flavour CTA procedure. Rates
      of lever-pressing of wild-type and mutant mice did not differ. Wild-type mice
      acquired discrimination of nicotine (0.4 or 0.8 mg/kg) rapidly and exhibited
      steep dose-response curves. Mutant mice failed to acquire these nicotine
      discriminations and exhibited flat dose-response curves. Both wild-type and
      mutant mice acquired discrimination of nicotine (1.6 mg/kg) although
      discrimination performance was weak in the mutants. Nicotine initially reduced
      response rates in wild-type and mutant mice, and tolerance developed to this
      effect in each genotype. Both genotypes acquired discrimination of morphine (3
      mg/kg) with similar degrees of accuracy, and dose-response curves for morphine
      discrimination in the two genotypes were indistinguishable. Nicotine produced
      dose-related CTA in both genotypes, but the magnitude of the effect was less in
      the mutants than in the wild-type controls. It is concluded that nicotinic
      receptors containing the beta2 subunit play a major role in the discriminative
      stimulus and taste aversion effects of nicotine that may reflect psychological
      aspects of tobacco dependence. Such receptors appear to have a less crucial role
      in the response-rate, reducing effects of nicotine and in nicotine tolerance.

PMID- 11955524
TI  - Impairing the amphetamine conditioning in rats through the inhibition of
      hippocampal calcium/calmodulin-dependent protein kinase II activity.
AB  - Amphetamine is an addictive drug, possessing reinforcing properties that are
      believed to be associated with an environmental cue, which resembles a behavioral
      learning process. This study investigates the role of calcium/calmodulin
      dependent protein kinase II (CaM-kinase II) in the acquisition of the amphetamine
      produced conditioned place preference (CPP). In Experiment I, rats were trained
      in an amphetamine-produced (2 mg/kg, i.p.) CPP task. The amphetamine-saline
      pairing rats spent significantly more time in the box that was associated with
      the amphetamine injection. Moreover, these rats' hippocampal CaM-kinase II showed
      significantly higher Ca(2+)-independent activity than that of the controls. In
      experiment II, the rats received an intra-hippocampal or intra-accumbens
      injection of specific CaM-kinase II inhibitor (KN-93) or a controlled agent (KN
      92) before training in the amphetamine-produced CPP task. The rats receiving the
      preconditioning intra-hippocampal KN-93 injection showed no amphetamine-produced
      CPP effect. These results, taken together, indicate that the biological basis of
      amphetamine-produced place preference behavior might be regulated by the
      hippocampal CaM-kinase II activity.

PMID- 11955525
TI  - Central leptin gene delivery evokes persistent leptin signal transduction in
      young and aged-obese rats but physiological responses become attenuated over time
      in aged-obese rats.
AB  - The purpose of this study was to determine if long-term leptin treatment
      desensitizes leptin signal transduction and the subsequent downstream anorexic
      and thermogenic responses in normal and leptin-resistant age-related obese rats.
      To this end, we administered, i.c.v., recombinant adeno-associated virus encoding
      rat leptin cDNA (rAAV-leptin) or control virus into young and aged-obese rats and
      after 9 or 46 days, examined food intake, oxygen consumption, body weight, serum
      leptin, STAT3 phosphorylation, hypothalamic NPY and POMC mRNAs, and UCP1
      expression and protein level in brown adipose tissue (BAT). In young rats, rAAV
      leptin depleted body fat and both anorexic and thermogenic mechanisms contributed
      to this effect. Moreover, leptin signal transduction was not desensitized, and
      there were persistent physiological responses. Similarly, in the aged-obese rats,
      there was unabated leptin signal transduction, however, both the anorexic and
      thermogenic responses completely attenuated sometime after day 9. This
      attenuation, downstream of the leptin receptor, may be contributing to the leptin
      resistance and age-related weight gain in these aged-obese rats. Finally, in
      young rats, although the initial responses to rAAV-leptin were dominated by
      anorexic responses, by 46 days, the predominant response was thermogenic rather
      than anorexic, suggesting that energy expenditure may be an important component
      of long-term weight maintenance.

PMID- 11955526
TI  - Influence of sildenafil on copulatory behaviour in sluggish or normal ejaculator
      male rats: a central dopamine mediated effect?
AB  - The present study investigates the effects induced by sildenafil (1 mg/kg, p.o.)
      and the dopamine agonist, SND 919 (0.1 mg/kg, i.p.) on copulatory behaviour of
      male rats, categorized, on the basis of seven consecutive mating pre-tests, as
      sluggish and normal ejaculators (SE and NE, respectively). The data obtained show
      that sildenafil modifies both sexual arousal and ejaculatory mechanisms of
      copulation. It appears that, although it induced a facilitatory effect on
      ejaculation of all rats, similarly to SND 919, the lowering of ejaculatory
      threshold was achieved by means of a reduction of mount frequency and
      intromission frequency in SE and NE groups, respectively. Differently from SND
      919, sildenafil increased sexual arousal, diminishing post ejaculatory interval
      in SE animals and inter-intromission interval in both SE and NE rats. As the
      dopamine antagonist, (-)eticlopride (0.02 mg/kg, s.c.), significantly inhibited
      sildenafil-induced enhancement of sexual arousal in SE rats, it is suggested that
      the drug acts both peripherally and centrally.

PMID- 11955527
TI  - Efficacy of the non-peptide CGRP receptor antagonist BIBN4096BS in blocking CGRP
      induced dilations in human and bovine cerebral arteries: potential implications
      in acute migraine treatment.
AB  - Calcitonin gene-related peptide (CGRP) is a potent vasodilator in brain vessels
      and it has been implicated in the pathogenesis of migraine headache. Blocking
      post-junctional CGRP receptors, mediators of trigeminal-induced vasodilation, has
      been suggested as a potential antimigraine strategy. In this study, we tested the
      ability of a new non-peptide CGRP receptor antagonist, BIBN4096BS, to inhibit the
      CGRP-induced dilation in human and/or bovine brain vessels and compared it to
      that of the antagonist alpha-CGRP(8-37). BIBN4096BS and alpha-CGRP(8-37) both
      blocked the alpha-CGRP-induced dilation in bovine middle artery segments with
      respective potency (pK(B) values) of 6.3 and 7.8. In human pial vessels,
      BIBN4096BS was particularly potent. When tested at 10(-14)-10(-9) M
      concentrations, it induced a rightward shift in the alpha-CGRP concentration
      response curve and yielded a biphasic Schild plot suggesting interaction with
      more than one receptor population, as was also indicated by the significant best
      fit of the alpha-CGRP-induced dilation in human brain vessels with a two receptor
      site interaction. Schild plot analysis in the linear portion of the BIBN4096BS
      inhibition curve revealed interaction with one high affinity site (pA(2) value
      approximately 14). In bovine vessels, both alpha-CGRP(8-37) and BIBN4096BS
      concentration-dependently reversed a pre-established CGRP-induced dilation (
      approximately 59 and 85%, respectively), BIBN4096BS being approximately tenfold
      more potent than alpha-CGRP(8-37) (respective pIC(50) values of 7.5 and 6.75). In
      human middle cerebral and middle meningeal arteries, BIBN4096BS reversed the
      alpha-CGRP-induced dilation (> or =70%) by interaction with two different
      receptor populations: it exhibited a high affinity for one population (pIC(50)
      value approximately 13) and a lower affinity for the other (pIC(50) value
      approximately 8). The present data demonstrate that BIBN4096BS is a very potent
      antagonist that could, depending on its bioavailability and in vivo affinity, be
      of potential benefit in the acute treatment of migraine headache by blocking
      and/or reversing the CGRP-mediated dilation of intracranial vessels induced by
      activation of trigeminovascular afferents.

PMID- 11955528
TI  - Nimodipine prevents the effects of ethanol in tests of memory.
AB  - The effects of acute administration of the dihydropyridine calcium channel
      antagonist, nimodipine, were studied on the actions of ethanol in the radial arm
      maze and the object recognition test. In the former test, the effects of the
      drugs were examined on the performance in finding the four baited arms, after
      previous training in this task. Ethanol, at 1 g/kg, increased both the number of
      re-entries into baited arms (counted as errors of working memory) and the total
      number of arm choices required to complete the task. Administration of
      nimodipine, 10 mg/kg, with the ethanol, completely prevented the deleterious
      effects on memory in this task, but had no effects on the performance when given
      in the absence of ethanol. In the object recognition task, ethanol, 1 g/kg,
      significantly decreased the differences in the time spent exploring novel and
      familiar objects. Nimodipine, 10 mg/kg, given with the ethanol, completely
      prevented this effect, but nimodipine alone had no effects. The lack of changes
      in total exploration times indicated that the effects of ethanol in these tests
      were not due to loss of motor co-ordination or of alertness. The results are
      discussed in the light of the known actions of the drugs on brain function.

PMID- 11955529
TI  - Just how tainted has medicine become?

PMID- 11955530
TI  - Mothers, orphans, and prevention of paediatric AIDS.

PMID- 11955531
TI  - Hirschsprung's disease: dissecting complexity in a pathogenetic network.

PMID- 11955532
TI  - Severe pneumonia and a second antibiotic.

PMID- 11955533
TI  - Violence against women: a global burden.

PMID- 11955534
TI  - Methotrexate and mortality in patients with rheumatoid arthritis: a prospective
      study.
AB  - BACKGROUND: Methotrexate is the most frequent choice of disease-modifying
      antirheumatic therapy for rheumatoid arthritis. Although results of studies have
      shown the efficacy of such drugs, including methotrexate, on rheumatoid arthritis
      morbidity measures, their effect on mortality in patients with the disease
      remains unknown. Our aim was to prospectively assess the effect on mortality of
      methotrexate in a cohort of patients with rheumatoid arthritis. METHODS: Our
      cohort included 1240 patients with rheumatoid arthritis seen at the Wichita
      Arthritis Center, an outpatient rheumatology facility. Patients' details were
      entered into a computerised database at the time of their first clinic visit. We
      also obtained and recorded demographic, clinical, laboratory, and self-reported
      data at each follow-up visit (average interval 3.5 months). We estimated the
      mortality hazard ratio of methotrexate with a marginal structural Cox
      proportional hazards model. FINDINGS: 191 individuals died during follow-up.
      Patients who began treatment with methotrexate (n=588) had worse prognostic
      factors for mortality. After adjustment for this confounding by indication, the
      mortality hazard ratio for methotrexate use compared with no methotrexate use was
      0.4 (95% CI 0.2-0.8). Other conventional disease-modifying antirheumatic drugs
      did not have a significant effect on mortality. The hazard ratio of methotrexate
      use for cardiovascular death was 0.3 (0.2-0.7), whereas that for non
      cardiovascular deaths was 0.6 (0.2-1.2). INTERPRETATION: Our data indicate that
      methotrexate may provide a substantial survival benefit, largely by reducing
      cardiovascular mortality. This survival benefit of methotrexate would set a
      standard against which new disease-modifying antirheumatic drugs could be
      compared.

PMID- 11955535
TI  - Efficacy of three short-course regimens of zidovudine and lamivudine in
      preventing early and late transmission of HIV-1 from mother to child in Tanzania,
      South Africa, and Uganda (Petra study): a randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Large reductions in transmission of HIV-1 from mother to child have
      been achieved in more-developed countries due to the use of antiretrovirals.
      Short-course regimens, suitable for resource-poor countries, have also been shown
      to significantly reduce peripartum HIV-1 transmission. We assessed the efficacy
      of short-course regimens with zidovudine and lamivudine in a predominantly
      breastfeeding population. METHODS: We did a randomised, double-blind, placebo
      controlled trial in South Africa, Uganda, and Tanzania. Between June, 1996, and
      January, 2000, HIV-1-infected mothers were randomised to one of four regimens: A,
      zidovudine plus lamivudine starting at 36 weeks' gestation, followed by oral
      intrapartum dosing and by 7 days' postpartum dosing of mothers and infants; B, as
      regimen A, but without the prepartum component; C, intrapartum zidovudine and
      lamivudine only; or placebo. From Feb 18, 1998, onward, women were only
      randomised to one of the active treatment groups. Primary outcomes were HIV-1
      infection and child mortality at week 6 and month 18 after birth. Analysis was by
      intention to treat of those randomised before Feb 18, 1998. FINDINGS: 1797 HIV-1
      infected women were identified. Week 6 HIV-1 transmission rates were 5.7% for
      group A, 8.9% for group B, 14.2% for group C, and 15.3% for the placebo group.
      Respective relative risks for HIV-1 transmission in the treatment groups compared
      with placebo were 0.37 (95% CI 0.21-0.65), 0.58 (0.36-0.94), and 0.93 (0.62
      1.40). For the combined endpoint of HIV-1 infection and infant mortality at week
      6 rates were 7.0%, 11.6%, 17.5%, and 18.1%, respectively, with relative risks of
      0.39 (0.24-0.64), 0.64 (0.42-0.97), and 0.97 (0.68-1.38). 1081 (74%) of the women
      analysed initiated breastfeeding. Based on an interval-censored survival
      analysis, HIV-1 infection rates at month 18 were 15% (95% CI 9-23), 18% (12-26),
      20% (13-30) and 22% (16-30), respectively. INTERPRETATION: Although at week 6
      after birth, regimens A and B were effective in reducing HIV-1 transmission,
      benefits have diminished considerably after 18 months of follow-up. Introduction
      of short-course regimens to prevent mother-to-child transmission of HIV-1 in less
      developed countries should be accompanied by interventions to minimise the risk
      of subsequent transmission via breastfeeding.

PMID- 11955536
TI  - Treatment of active ankylosing spondylitis with infliximab: a randomised
      controlled multicentre trial.
AB  - BACKGROUND Treatment options for patients with ankylosing spondylitis are few. We
      aimed to assess the effectiveness of infliximab, an antibody to tumour necrosis
      factor (TNF)-alpha, in treatment of such patients. METHODS: In this 12-week
      placebo-controlled multicentre study, we randomly assigned 35 patients with
      active ankylosing spondylitis to intravenous infliximab (5 mg/kg) and 35 to
      placebo at weeks 0, 2, and 6. One patient in the infliximab group was withdrawn
      from the study. Our primary outcome was regression of disease activity of at
      least 50%. To assess response, we used validated clinical criteria from the
      ankylosing spondylitis assessment working group, including disease activity
      (BASDAI), functional indices (BASFI), metrology (BASMI), and quality of life
      (short form 36). Analyses were done by intention to treat. FINDINGS: 18 (53%) of
      34 patients on infliximab had a regression of disease activity at week 12 of at
      least 50% compared with three (9%) of 35 on placebo (difference 44% [95% CI 23
      61], p<0.0001). Function and quality of life also improved significantly on
      infliximab but not on placebo (p<0.0001 and p<0.0001, respectively). Treatment
      with infliximab was generally well tolerated, but three patients had to stop
      treatment because of systemic tuberculosis, allergic granulomatosis of the lung,
      or mild leucopenia. INTERPRETATION: Our results show that treatment with
      infliximab is effective in patients with active ankylosing spondylitis. Since
      there are some potentially serious adverse effects, we recommend that this
      treatment mainly be used in co-operation with rheumatological centres.

PMID- 11955537
TI  - Early and midterm outcome after off-pump and on-pump surgery in Beating Heart
      Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two
      randomised controlled trials.
AB  - BACKGROUND: Although no randomised controlled trial has assessed the midterm
      effects of coronary-artery bypass surgery on the beating heart, this technique is
      being used in more and more patients. We did two randomised trials to compare the
      short-term morbidity associated with off-pump and on-pump myocardial
      revascularisation. Our aim was to pool the results to assess midterm outcomes.
      METHODS: From March, 1997, to November, 1999, we randomly allocated 200 patients
      to off-pump and 201 to on-pump coronary surgery. In Beating Heart Against
      Cardioplegic Arrest Study (BHACAS) 1, we excluded patients who had had myocardial
      infarction in the past month or who required grafting of the circumflex artery
      distal to the first obtuse marginal branch. In BHACAS 2, we included such
      patients. Primary outcomes were all-cause mortality and cardiac-related events at
      midterm follow-up (1-3 years). Analysis was by intention to treat. FINDINGS:
      Analyses of combined data from both trials showed the following risk differences
      with off-pump compared with on-pump surgery: atrial fibrillation -25% (95% CI 
      33% to -16%); chest infection -12% (-19% to -5%); inotropic requirement -18% (
      25% to -10%); transfusion of red blood cells -31% (-41 to -21); and hospital stay
      longer than 7 days -13% (-21 to -5). Mean follow-up was 25 0 months (SD 9.1) for
      BHACAS 1 and 13.7 months (5 5) for BHACAS 2. Four (2%) of 200 patients in the off
      pump groups died from any cause, compared with seven (3%) of 201 in the on-pump
      group (hazard ratio 0.57, 95% CI 0.17-1.96). 33 (17%) of 200 patients in the off
      pump group died or had a cardiac-related event, compared with 42 (21%) of 201 in
      the on-pump group (0.78, 0 49-1.22). INTERPRETATION: Off-pump coronary surgery
      significantly lowers in-hospital morbidity without compromising outcome in the
      first 1-3 years after surgery compared with conventional on-pump coronary
      surgery.

PMID- 11955538
TI  - Aching alopecia.

PMID- 11955539
TI  - Association between c135G/A genotype and RET proto-oncogene germline mutations
      and phenotype of Hirschsprung's disease.
AB  - BACKGROUND: Several genes, including the major susceptibility gene RET, have
      roles in development of Hirschsprung's disease. Results of genetic-linkage
      analysis of patients with familial disease with both long-segment and short
      segment phenotypes have shown close linkage with the RET locus. We aimed to
      investigate whether both RET mutations and polymorphisms contribute to phenotype
      of Hirschsprung's disease. METHODS: We looked at the coding region of all 21
      exons of the RET proto-oncogene, including the flanking intronic sequences, by
      direct DNA sequencing in 76 caucasians from Germany with Hirschsprung's disease.
      FINDINGS: 20 different mutations were detected in 18 patients. Mutations were
      under-represented in patients with a homozygous RET c135A/A genotype in
      association with short-segment phenotype. Short-segment phenotype also arose if
      the RET mutation was on the c135A allele; conversely, a RET germline mutation on
      the c135G allele resulted in long-segment phenotype, particularly in heterozygous
      c135G/A patients. INTERPRETATION: These observations lend support to the idea
      that both RET alleles have a role in pathogenesis of Hirschsprung's disease, in a
      dose-dependent fashion. We also showed that the c135G/A polymorphism modifies the
      phenotype by a within-gene interaction between the c135A variant and a mutation.

PMID- 11955540
TI  - A pain in the neck.

PMID- 11955541
TI  - Comparison of upper airway collapse during general anaesthesia and sleep.
AB  - Measurement of the collapsibility of the upper airway while a patient is awake is
      not a good guide to such collapsibility during sleep, presumably because of
      differences in respiratory drive, muscle tone, and sensitivity of reflexes. To
      assess whether a relation existed between general anaesthesia and sleep, we
      measured collapsibility of the upper airway during general anaesthesia and
      severity of sleep-disordered breathing in 25 people who were having minor surgery
      on their limbs. Anaesthetised patients who needed positive pressure to maintain
      airway patency had more severe sleep-disordered breathing than did those whose
      airways remained patent at or below atmospheric pressure. Such an association was
      strongest during rapid-eye-movement (REM) sleep. Our findings suggest that sleep
      disordered breathing should be considered in all patients with a pronounced
      tendency for upper airway obstruction during anaesthesia or during recovery from
      it.

PMID- 11955542
TI  - Terlipressin for norepinephrine-resistant septic shock.
AB  - Norepinephrine-resistant hypotension when associated with septic shock has a high
      rate of mortality, which might possibly be reduced by infusion of low-dose
      vasopressin. However, rebound hypotension often arises after treatment is
      stopped, and the drug usually has to be administered for several days. We report
      use of terlipressin, a long-acting vasopressin analogue, in eight patients with
      septic shock who did not respond to corticosteroids and methylene blue. A
      significant rise in blood pressure that lasted for at least 5 h was seen in all
      patients after a single bolus, allowing reduction or cessation of norepinephrine
      administration in seven patients. We were able to discharge four patients from
      intensive care subsequently. Terlipressin seems to be an effective rescue
      therapy, which is able to restore blood pressure in patients with catecholamine
      resistant septic shock, without obvious complication.

PMID- 11955544
TI  - US panel calls for more support of alternative medicine.

PMID- 11955543
TI  - Vitamin A deficiency and genital viral burden in women infected with HIV-1.
AB  - The relation between vitamin A (retinol) deficiency and perinatal transmission of
      HIV-1, if it exists, might be mediated through an increased viral load in the
      mother's genital tract. To ascertain whether or not such an association is
      present, we measured the serum concentration of retinol with high performance
      liquid chromatography, and correlated the results with concurrent quantified HIV
      1 RNA concentrations in cervicovaginal lavage fluid in 301 women infected with
      the virus. We noted no association between retinol status and genital HIV-1 load.
      Our findings lend support to those of studies that reported no association
      between retinol deficiency and perinatal HIV-1 transmission.

PMID- 11955546
TI  - Researchers uncover a shared mechanism for protein aggregation disorders.

PMID- 11955549
TI  - Adeno-associated virus vectors under scrutiny.

PMID- 11955550
TI  - Bush's choices for NIH chief and Surgeon General.

PMID- 11955551
TI  - Hopes for the restoration of Argentine health services.

PMID- 11955553
TI  - World Bank allocates funds to help war-torn Sierra Leone fight HIV/AIDS.

PMID- 11955555
TI  - Medical students learn to cater for healthy appetites.

PMID- 11955556
TI  - Multiple sclerosis.
AB  - Multiple sclerosis is the prototype inflammatory autoimmune disorder of the
      central nervous system and, with a lifetime risk of one in 400, potentially the
      most common cause of neurological disability in young adults. As with all complex
      traits, the disorder results from an interplay between as yet unidentified
      environmental factors and susceptibility genes. Together, these factors trigger a
      cascade of events, involving engagement of the immune system, acute inflammatory
      injury of axons and glia, recovery of function and structural repair, post
      inflammatory gliosis, and neurodegeneration. The sequential involvement of these
      processes underlies the clinical course characterised by episodes with recovery,
      episodes leaving persistent deficits, and secondary progression. The aim of
      treatment is to reduce the frequency, and limit the lasting effects, of relapses,
      relieve symptoms, prevent disability arising from disease progression, and
      promote tissue repair. Despite limited success in each of these categories,
      everyone touched by multiple sclerosis looks for a better dividend from applying
      an improved understanding of the pathogenesis to clinical management.

PMID- 11955558
TI  - From ugly fish to conquer death: J J R Macleod's fish insulin research, 1922-24.
AB  - Fish insulin research had a very short heyday. Throughout most of 1922,
      production of insulin from livestock was difficult, erratic, and expensive.
      Although fish insulin was easy to extract and seemed to be a brilliant and
      logical solution to the shortage of insulin, collection of fish islets was a
      logistical nightmare. By the end of 1922, a scientist at the pharmaceutical
      company Eli Lilly in Indianapolis, IN, USA had developed a way to concentrate and
      purify insulin by isoelectric precipitation. As a result of this breakthrough,
      the scales began to tip heavily in favour of livestock insulin. Nevertheless,
      research on commercial production of fish insulin continued for another 18 months
      but was finally abandoned.

PMID- 11955557
TI  - Violence against women: global scope and magnitude.
AB  - An increasing amount of research is beginning to offer a global overview of the
      extent of violence against women. In this paper we discuss the magnitude of some
      of the most common and most severe forms of violence against women: intimate
      partner violence; sexual abuse by non-intimate partners; trafficking, forced
      prostitution, exploitation of labour, and debt bondage of women and girls;
      physical and sexual violence against prostitutes; sex selective abortion, female
      infanticide, and the deliberate neglect of girls; and rape in war. There are many
      potential perpetrators, including spouses and partners, parents, other family
      members, neighbours, and men in positions of power or influence. Most forms of
      violence are not unique incidents but are ongoing, and can even continue for
      decades. Because of the sensitivity of the subject, violence is almost
      universally under-reported. Nevertheless, the prevalence of such violence
      suggests that globally, millions of women are experiencing violence or living
      with its consequences.

PMID- 11955559
TI  - Research in complex diseases.
AB  - Many diseases that have a substantial effect on health have a complex
      pathogenesis. Examples are atherosclerosis, diabetes mellitus, and rheumatoid
      arthritis. Here, we discuss a hierarchy of goals of research in complex diseases,
      and introduce a stepwise approach for the development of disease models, paying
      specific attention to the position of genetic factors and stochastic variables in
      these models.

PMID- 11955560
TI  - Communication.

PMID- 11955561
TI  - Seasonality of birth in patients with type 1 diabetes.

PMID- 11955562
TI  - Seasonality of birth in patients with type 1 diabetes.

PMID- 11955563
TI  - Seasonality of birth in patients with type 1 diabetes.

PMID- 11955565
TI  - Seasonality of birth in patients with type 1 diabetes.

PMID- 11955566
TI  - Insulinotropic meglitinide analogues.

PMID- 11955567
TI  - Risk reduction for stroke and coronary events.

PMID- 11955568
TI  - Risk reduction for stroke and coronary events.

PMID- 11955569
TI  - Risk reduction for stroke and coronary events.

PMID- 11955571
TI  - Transient aspergillus antigenaemia: think of milk.

PMID- 11955572
TI  - Ruptured intracerebral abscess.

PMID- 11955573
TI  - Infliximab-induced aseptic meningitis.

PMID- 11955574
TI  - Risk factors for mortality in acute myocardial infarction.

PMID- 11955576
TI  - Suture of second-degree perineal tears after childbirth.

PMID- 11955577
TI  - Dickens: an alternative diagnosis.

PMID- 11955578
TI  - Bringing global issues to medical teaching.

PMID- 11955579
TI  - Avoiding the point.

PMID- 11955581
TI  - Avoiding unnecessary risks to our children.

PMID- 11955583
TI  - Discarded diagnoses.

PMID- 11955590
TI  - The war of eye and ear.

PMID- 11955593
TI  - A structural perspective on MHC class I recognition by killer cell immunoglobulin
      like receptors.
AB  - Killer cell immunoglobulin-like receptors (KIR) play a critical role in the
      regulation of natural killer (NK) cell activity through their recognition of
      class I MHC molecules expressed on target cells. KIR recognition provides vital
      information to NK cells about whether a target cell should be lysed or spared.
      Understanding the molecular mechanism of this recognition has remained a strong
      focus of investigation. This has resulted in the crystal structures of several
      members of the KIR family and more recently the determinations of the three
      dimensional structures of KIR2DL2 and KIR2DL1 complexed with their respective
      ligands, HLA-Cw3 and HLA-Cw4. A strong structural conservation has been revealed
      both in the receptor design and in the overall mode of KIR binding to class I
      molecules. Nevertheless, distinct differences in the receptor binding sites allow
      for high specificity between ligands. Furthermore, unexpected similarities with T
      cell receptor (TCR) recognition of MHC molecules are also observed. The detailed
      interactions between KIR and HLA-C molecules and their functional implications
      will be reviewed here.

PMID- 11955594
TI  - MHC class I recognition by Ly49 natural killer cell receptors.
AB  - Natural killer (NK) cell function is regulated by NK receptors that bind either
      classical MHC class I (MHC-I) molecules or their structural relatives (MICA, RAE
      1 and H-60). Two distinct families of NK receptors have been identified: the C
      type lectin-like family (Ly49, NKG2D and CD94/NKG2) and the immunoglobulin-like
      family (KIRs and LIRs). Here, we describe the crystal structure of the C-type
      lectin-like NK receptor (Ly49A), bound to its MHC-I ligand (H-2D(d)). We also
      discuss results from recent mutagenesis studies of the Ly49A/H-2D(d) interaction
      in the context of the complex structure.

PMID- 11955595
TI  - Asymmetric ligand recognition by the activating natural killer cell receptor
      NKG2D, a symmetric homodimer.
AB  - Natural killer (NK) cells function through a diverse array of cell-surface
      natural killer receptors (NCRs). NCRs specific for classical and non-classical
      MHC class I proteins, expressed in complex patterns of inhibitory and activating
      isoforms on overlapping, but distinct, subsets of NK cells, play an important
      role in immunosurveillance against cells that have reduced MHC class I expression
      as a result of infection or transformation. Another NCR, NKG2D, is an activating
      NCR first identified on NK cells, but subsequently found on macrophages and a
      variety of T cell types. NKG2D ligands in rodents include the MHC class I-like
      proteins RAE-1 and H60 and, in humans, ULBPs and the cell stress-inducible
      proteins MICA and MICB. NKG2D-MIC and -RAE-1 recognition events have been
      implicated in anti-viral and -tumor immune responses. Crystallographic analyses
      of NKG2D-MICA and -RAE-1 complexes reveal an unusual mode of recognition that
      apparently tolerates a surprising degree of ligand plasticity while generating
      affinities that are among the strongest TCR- or NCR-ligand affinities, thus, far
      described.

PMID- 11955596
TI  - Structural basis of T cell recognition of peptides bound to MHC molecules.
AB  - Helper T lymphocytes play a critical role in immune system activation following
      recognition of MHC class II-bound peptide ligands (pMHCII). These CD4 T cells
      stimulate B cell antibody production and cytolytic T cell generation. Until
      recently, the structural basis of coordinate T cell receptor (TCR) and CD4 co
      receptor interaction with a given pMHCII was unknown. Here we review current
      structural data on specific pMHCII recognition by T cells and compare TCR and co
      receptor docking to pMHCI versus pMHCII ligands. The implications of these
      findings for thymic selection, helper versus cytolytic T cell recognition and
      alloreactivity are discussed.

PMID- 11955597
TI  - Structure of gammadelta T cell receptors and their recognition of non-peptide
      antigens.
AB  - The gammadelta T cell receptors (TCRs) and alphabeta TCRs are similar in both
      sequence and structure; however, gammadelta+ and alphabeta+ T cells are not
      merely similar lymphocytes with subtly different receptors. These cell types
      differ in several ways, including the types of antigens recognized, the mechanism
      of antigen presentation and recognition and the mechanism and kinetics of
      downstream signaling events. gammadelta TCRs can directly recognize antigens in
      the form of intact proteins or non-peptidic compounds, unlike alphabeta TCRs
      which recognize peptide antigens bound to major histocompatibility complex
      molecules (MHC). One of the major classes of human gammadelta+ T cells expresses
      Vgamma9Vdelta2 TCRs which recognize pyrophosphomonoester, alkylamine and
      aminobisphosphonate antigens. This review focuses on the recently determined
      structure of a Vgamma9Vdelta2 TCR, with emphasis on antigen recognition and
      receptor signaling.

PMID- 11955598
TI  - Structural insights into the interactions between human IgE and its high affinity
      receptor FcepsilonRI.
AB  - The interaction of IgE antibodies with the high affinity IgE receptor,
      FcepsilonRI, is a key step in the initiation of anti-parasitic immunity and
      allergic reactions. Recent structural studies of the receptor, the IgE-Fc and the
      IgE-Fc:FcepsilonRI complex have revealed how these two proteins interact to prime
      mast cell responses to antigen. The structures have revealed a novel arrangement
      for the FcepsilonRI ectodomains that is also observed in homologous members of
      this antibody receptor family. The crystal structure of the IgE-Fc:FcepsilonRI
      complex clarified how a 1:1 complex between the antibody and receptor is formed,
      with the receptor binding each chain of the antibody Fc dimer. The IgE-Fc
      structure in the absence of the receptor revealed the potential for large
      conformational rearrangements within the IgE that may affect receptor binding.
      These studies provide the basis for further investigation of the specificity of
      antibody:receptor binding and for the development of new treatments for allergic
      hypersensitivities.

PMID- 11955599
TI  - Recognition of immunoglobulins by Fcgamma receptors.
AB  - Fc receptors mediate antibody dependent inflammatory response and cytotoxicity as
      well as certain autoimmune dysfunctions. Fcgamma receptors interact with IgG
      antibodies by binding the Fc portion of the antibody in asymmetric fashion
      creating a 1:1 receptor-ligand stoichiometry. Regions of the C-terminal domain of
      Fc receptors including the BC, C'E, FG loops, and the C' beta-strand interact
      with immunoglobulins. The lower hinge region of the antibody contributes most of
      the binding to the low affinity Fcgamma receptors. Carbohydrates attached to the
      conserved glycosylation site on Fc portion of an antibody are critical to the
      recognition of immunoglobulins by the low affinity Fcgamma receptor. They are
      likely to function as a substitution for the hydrophobic core to preserve an
      optimal lower hinge conformation for the receptor binding. Subtype specificities
      of FcgammaRIII receptor probably are determined by the length of the lower hinge
      regions of immunoglobulins, but not their amino acid composition as revealed by
      the binding study of the lower hinge peptides. These studies also paved a new way
      for designing of novel therapeutic compounds in fighting autoimmune diseases.

PMID- 11955600
TI  - Cochlear implantation in prelingually deafened children with residual hearing.
AB  - OBJECTIVE: The purpose of this study was to examine the speech perception skills
      of prelingually deafened French children with preoperative residual hearing who
      received multichannel cochlear implants. DESIGN: The design of the study
      incorporated a within-subject, repeated measures design for assessing speech
      perception skills. SETTING: Montpellier, Toulouse and Lyon Pediatric Cochlear
      Implant Centers. SUBJECTS: Seven prelingually deafened children demonstrating
      marginal benefit from conventional amplification prior to implantation with a
      Nucleus multichannel cochlear implant, served as subjects for the speech
      perception assessment (a speech recognition score less than 30% defines marginal
      benefit from acoustic amplification on open set materials). The mean age at
      implantation was 7 years, 9 months. OUTCOME MEASURES: Speech perception skills
      were assessed using open set materials and the MUSS and MAIS questionnaires.
      RESULTS: Open-set speech recognition averaged 21.4% before implantation, and
      83.6% after 1 year's cochlear implant experience. All children demonstrated an
      open-set score over 60% after 12 months of CI use. MAIS test scores averaged
      18.1/40 before implantation and 35.1/40 after 9 months of CI use. MUSS test
      scores averaged 24.4/40 before implantation and 34.1/40 after 9 months of CI use.
      CONCLUSIONS: Cochlear implantation should be considered for prelingually hearing
      impaired children demonstrating marginal benefit from hearing aids, with a speech
      recognition score less than 30% on open set materials, in order to improve their
      speech discrimination skills.

PMID- 11955601
TI  - Histopathologic differences due to bacterial species in acute otitis media.
AB  - OBJECTIVE: To compare selected features of histopathology in acute otitis media
      caused by various bacteria and examine potential differences due to bacterial
      species, as well as possible correlation to experimental and human clinical
      findings. METHODS: Rat models of acute otitis media caused by Streptococcus
      pneumoniae (MC), non-typeable or type b Haemophilus influenzae (NTHI/HIB) or
      Moraxella catarrhalis (MC) were studied longitudinally up to 6 months after
      bacterial challenge. Findings related to dynamics of goblet cell density,
      modeling and remodeling of bone tissue structures and polyp, as well as fibrous
      adhesion formation and persistence are presented. RESULTS: Middle ear goblet cell
      density progressed to peak 2 weeks after bacterial inoculation, thereafter
      gradually normalizing. However, density and accordingly middle ear secretory
      capacity was still significantly increased after 6 months in all bacteria, except
      MC. The HI species induced the highest increase. Initial osteoresorption was
      followed by massive osteoneogenesis, progressing to a peak after 2-3 months,
      followed by some degree of normalization, concurrently classic remodeling.
      Primarily SP, but also the HI species induced more new bone formation than MC.
      Mucosal polyp and fibrous adhesion formation occurred regardless of bacterial
      species. Most polyps appeared in the early phases and the HI species induced
      formation of more polyps and adhesions than the other bacteria. CONCLUSION: Acute
      middle ear infection with the Haemophilus species induce the highest increase of
      mucosal secretory capacity, lasting for at least 6 months after the acute
      incident. Thus, a subsequent development of secretory otitis media seems more
      likely following infection with these bacteria. Equivalently, mucosal scarring
      observed as polyp and fibrous adhesion formation was more severe following
      Haemophilus infection. S. pneumoniae induced the most marked changes of bone
      tissue structures, seen as initial osteoresorption and subsequent
      osteoneogenesis. Overall, infection with M. catarrhalis induced the mildest
      changes.

PMID- 11955602
TI  - A preventive measure for otitis media in children with upper respiratory tract
      infections.
AB  - Recurrent upper respiratory tract infections (URTI) are very common in patients
      of all ages. Rhinitis, bronchitis, chronic sinusitis and otitis appear to be the
      prevalent forms of recurrent respiratory infections in the paediatric population.
      The aim of treatment is so the solution of the respiratory pathology and the also
      the prevention of their complications. Antibacterial therapy is still the
      classical treatment approach in patients both with respiratory tract infections
      and with otitis media, despite the fact that antibacterials have several well
      known drawbacks, especially when used to treat recurrent infections. Eighty-four
      paediatric patients of both sexes (range: 4-14 years) with otitis were enrolled
      in the study. Patients were included if they had a >2 years' history of recurrent
      or chronic respiratory infections, and/or had experienced at least three episodes
      requiring medical consultations and/or treatment during the winter prior to the
      study. The young patients were randomised to receive Immucytal (group A) or
      placebo (group B) treatment according to the following protocol: (1) starting
      therapy (1 month): one tablet daily in the morning 4 days per week for 3
      consecutive weeks; (2) maintenance period (5 months): one tablet daily in the
      morning 4 days per week for 1 week every month. Placebo and Immucytal tablets
      were identical in shape and size, in order to maintain double-blind conditions.
      Patients of group A with recurrent URTI had a significantly decreased incidence
      of ENT infections, fever and shorter duration of illness, decreased requirement
      for ancillary medications and fewer work-days lost. The reduction in the
      incidence of infectious episodes became significant vs. placebo. A significantly
      improved outcome vs. placebo was also observed on the incidence of fever,
      frequency and duration of infectious episodes, ancillary therapies. Immucytal
      treatment was associated with significant changes in both immunological and
      auditory function parameters. Serum concentrations of immunoglobulins were
      significantly increased in Immucytal. For both evaluations, a significant
      difference between treatment groups was found (P>0.001). Preventive strategies,
      such as ribosomal immunotherapy, may represent a valid alternative approach.

PMID- 11955603
TI  - Cephalometric evaluation of facial types in preschool children without sleep
      related breathing disorder.
AB  - OBJECTIVE: this study was aimed at characterizing the craniofacial structures,
      i.e. the facial skeleton, cranial base, dentition, pharyngeal airway space, and
      the hyoid bone position, in healthy preschool children without sleep-related
      breathing disorder. MATERIALS AND METHODS: from lateral cephalometric radiographs
      taken of 92 children for diagnostic purposes, 45 were selected for the present
      investigation on the basis of head position, and divided according to the
      classification of Siriwat and Jarabak (Angle Orthod. 55 (1985) 127) into groups
      representing counter-clockwise (CC), straight downward (SD), and clockwise (C)
      facial types. RESULTS: the findings showed that, in comparison with the other
      groups, CC is associated with larger facial taper and posterior facial height,
      smaller mandibular line angle, ramus position, lower facial height and cranial
      base angle. By a similar comparison, C is associated with larger mandibular line,
      gonial angles and convexity, and with a smaller L-1 to mandibular line angle.
      There were no significant differences in hyoid bone position among the three
      groups. However, the distance of the lower pharynx was smaller in CC than in C,
      while the tongue base of CC was noted to be in a posterior position. CONCLUSIONS:
      thus, the results indicate that there are significant differences in the
      madibular position and form among the present three groups of children. It is
      proposed that the objective of vertical facial control ought to be included in
      the treatment of preschool children with malocclusion and respiratory disorder.

PMID- 11955604
TI  - Efficacy of speech therapy in children with language disorders: specific language
      impairment compared with language impairment in comorbidity with cognitive delay.
AB  - OBJECTIVE: this article discusses the effect of speech therapy on language
      comprehension, language production and non-verbal functioning in two groups of
      children with developmental language disorders. DESIGN: retrospective study-a
      follow-up after a mean of 2 years. MATERIALS AND METHODS: verbal and non-verbal
      functioning before and after therapy were examined in 31 language-impaired
      children with normal hearing and good health. In 16 children the language
      functioning was substantial behind their non-verbal functioning. They were
      categorised as children with specific language impairment (SLI). In 15 children
      the language problem was in comorbidity with cognitive delay, and these were
      categorised as children with non-SLI. At the first examination the children were
      at the age of 1;5-5;4 years and at the second examination they were at the age of
      3;4-6;11 years. The children were examined for language comprehension
      (Standardised Dutch version of the Reynell Developmental Comprehension Scale),
      spontaneous language production (Groningen Diagnostic Speech norms) and non
      verbal functioning (Snijders-Oomen non-verbal intelligence scale for children
      between 2 1/2 and 7 years). RESULTS: in both groups, a significant improvement
      was found in language functioning as well as in non-verbal functioning. Language
      comprehension and non-verbal IQ-scores in both groups improved by about the same
      amount. Language production made significantly more progress in the SLI group
      than in the non-SLI group. The improvements in the SLI group were mainly reached
      by speech therapy, whereas in the non-SLI group this was less the case.
      CONCLUSIONS: verbal and non-verbal development can improve in young children with
      developmental language delay. This underlines the idea that language and
      cognitive development are interacting and influencing each other in a positive
      way. Children with SLI seem to benefit more from speech therapy, whereas children
      with cognitive delay seem to benefit more from special education.

PMID- 11955605
TI  - Cantonese tone perception ability of cochlear implant children in comparison with
      normal-hearing children.
AB  - BACKGROUND AND OBJECTIVE: Cantonese is a tone language. A change in the
      fundamental frequency pattern within the same phonemic segment causes a change in
      the lexical meaning. The present study examined the Cantonese tone perception
      ability of cochlear implant children in comparison with normal-hearing children.
      It was hypothesized that cochlear implant children follow a similar pattern of
      tone perception development, as do normal children. METHOD: 225 normal-hearing
      and 15 hearing-impaired children with cochlear implants were recruited. The high
      level (tone 1), high rising (tone 2) and low falling (tone 4) were the target
      tones examined. The three tones were arranged into tone pairs for identification.
      Each pair shared exactly the same segmental information but differed only in
      tones (e.g. /sy/ in tones 1 and 2 meaning 'book' and 'mouse', respectively).
      Subjects were required to point to the corresponding pictures after the live
      voice presentations. RESULTS: for each tone pair, each subject was awarded a
      score representing the proportion of stimuli pairs that were correctly
      discriminated by the subject. The average scores in the normal-hearing and
      hearing-impaired groups were 0.92 and 0.64, respectively. The normal group had
      the lowest average score in tone 2/tone 4 (0.87) while the hearing-impaired group
      performed the worst in tone 1/tone 2 (0.53) perception between the three tone
      contrasts. CONCLUSIONS: the normal-hearing group performed significantly better
      than the hearing-impaired group in basic Cantonese tone perception. The pattern
      of tone perception development of cochlear implant children did not seem to
      follow that of normal children. Contributing factors on the tone perception
      performance of the cochlear implant children were subject's age, duration of
      special training, and durations of wearing the hearing aid and the cochlear
      implant.

PMID- 11955606
TI  - Possible inflammatory mediators in tympanosclerosis development.
AB  - OBJECTIVE: Tympano/myringosclerosis is a sequelae following otitis media, causing
      hearing disability. There is no curative treatment for this condition. In order
      to illuminate the correlation of inflammatory mediators in otitis media and
      tympanosclerosis development, the present study was performed. METHODS: In an
      animal model, Streptococcus pneumonia bacteria were inoculated to the middle ear.
      Furthermore, biopsies were harvested during surgery, from children suffering from
      secretory otitis media and from patients with already established
      tympanosclerosis. The early inflammatory parameters were investigated in the rat
      model as well as in the patient material. The lymphocytic population,
      macrophages, interleukin-6, inducible nitric oxide synthase and MHC class II were
      studied by immunohistochemistry and by mRNA in situ hybridization. RESULTS:
      Myringosclerosis was produced in 30% of the rats studied. Macrophages were the
      first cells to invade the middle ear after induction of otitis media, followed by
      B-cells and T-cells. IL-6 m-RNA was found as early as 1 h after inoculation.
      Cells, expressing inducible nitric oxide synthase, seemed to be activated
      macrophages. Osteoclast like cells, positive in immunohistechemical macrophage
      staining, were found close to the insertion of the tympanic membrane. The human
      specimens showed a more immunological active stage in the secretory otitis media
      group as compared to the specimens with tympanosclerosis. CONCLUSIONS: The
      immunocompetent cells and some mediators are presented time dependently in otitis
      media and a possible reaction sequence, leading to differentiation of macrophages
      into osteoclasts is presented. This may lead to tympanosclerosis development.

PMID- 11955607
TI  - Primary neuroblastoma of the maxillary sinus.
AB  - Although neuroblastoma is the most common of extracranial solid tumors of
      childhood and infancy, we report the first case of an isolated neuroblastoma of a
      paranasal sinus. A 15-year-old girl with a right maxillary sinus mass was
      asymptomatic except for persistent epiphora. Computed tomography and magnetic
      resonance imaging scans showed that the mass extended into the nasal cavity,
      encroached on the lamina papyracea, and obstructed the nasofrontal duct. An
      extensive workup revealed no evidence of systemic disease. The patient underwent
      right craniofacial resection. Immunohistochemistry and electronmicroscopic
      findings were consistent with conventional neuroblastoma. Fluorescence in situ
      hybridization analysis was performed with probes selected to demonstrate genetic
      alterations associated with neuroblastoma. Studies revealed deletion of
      chromosome arm 1p, gain of chromosome 17, and normal N-myc gene copy number. In
      summary, the tumor exhibited morphologic features and genetic alterations more
      consistent with those of neuroblastoma than with those of esthesioneuroblastoma.

PMID- 11955608
TI  - Cloning and characterization of the C. elegans gas1 homolog: phas-1.
AB  - Among the set of genes expressed during the quiescent G0 phase of the cell cycle
      (gas genes), gas1 encodes for a GPI anchor protein associated to the plasma
      membrane, which is able to induce growth arrest when overexpressed in
      proliferating fibroblasts. In this report we describe the isolation and
      characterization of a gas1 Caenorhabditis elegans homolog, phas-1, that seems to
      be transcribed as an operon together with a gene encoding for a protein similar
      to human acid ceramidases. Phas-1 structure is very similar to its mammalian
      homolog conserving almost all cysteine residues and it is expressed in the
      pharynx from its early formation, in the two-fold embryo, until the adult stage.
      Surprisingly, while phas-1 is expressed in all developmental stages, with the
      exception of the dauer larva, the ceramidase-like encoding gene, co-expressed in
      the same operon together with phas-1, is absent in embryos and is very abundantly
      expressed in the dauer larva. Overexpression of phas-1 in growing NIH3T3
      fibroblasts is able to inhibit the S-phase entry in a similar manner as its
      murine homolog. On the other hand, when phas-1 is overexpressed or ablated in C.
      elegans, no specific phenotype due to its transcription alteration can be
      observed, despite its localized expression suggesting a role in pharynx function
      or development.

PMID- 11955609
TI  - Postmortem stability of RNA isolated from bovine reproductive tissues.
AB  - Molecular biology is being increasingly used to address the complex problem of
      bovine infertility. One common concern shared by many of these studies is the
      postmortem delay in obtaining reproductive tissues and the effect this may have
      on RNA dependent studies. To address this concern, bovine ovarian, oviduct and
      uterine tissue samples, collected over intervals ranging from 0 to 96 h
      postmortem to freeze storage, were analysed to determine the potential effects on
      RNA quantity and quality. The analysis showed that total RNA yields were not
      changed significantly by postmortem interval up to 96 h while 28S ribosomal RNA
      remained intact up to 24 h postmortem. Specific messenger RNA transcripts
      encoding beta-actin, GAPDH and transforming growth factor-beta were detected in
      all tissues up to 96 h postmortem using reverse transcriptase-polymerase chain
      reaction and Northern analysis indicated no detectable mRNA degradation up to 24
      h postmortem. Finally, using poly(A)(+) mRNA isolated from ovarian tissues frozen
      2 h postmortem, we constructed corpus luteum and ovarian cortex cDNA libraries
      containing 7.65x10(4) and 1.9x10(6) primary transformants with average cDNA
      lengths of 2.3 and 1.6 kb respectively. Taken together, these data show that a
      postmortem delay of up to 24 h does not significantly affect the yield or quality
      of RNA prepared from bovine reproductive tissues.

PMID- 11955610
TI  - Mitf-D, a newly identified isoform, expressed in the retinal pigment epithelium
      and monocyte-lineage cells affected by Mitf mutations.
AB  - Microphthalmia-associated transcription factor (Mitf) regulates the
      differentiation of melanocytes, optic cup-derived retinal pigment epithelium
      (RPE), and some types of bone marrow-derived cells. Mitf consists of at least
      five isoforms with different N-termini, each of which is encoded by a separate
      exon 1. Here we identified a novel isoform, termed mouse Mitf-D/human MITF-D,
      that is expressed in RPE, macrophages, and osteoclasts affected by the Mitf
      mutations, but not expressed in other Mitf target cells, including melanocyte
      lineage cells and natural killer cells. The initiation Met of MITF-D is located
      in the downstream domain (B1b domain) that is shared by other MITF isoforms. The
      5'-untranslated region of MITF-D mRNA is encoded by the newly identified first
      exon of the MITF gene, termed exon 1D, which is located 3 kb upstream of the exon
      encoding the B1b domain. Thus, the MITF gene generates multiple isoforms with
      different expression patterns by using the alternative promoters in a cell
      dependent manner, thereby providing the molecular basis for the phenotypic
      variability seen in the MITF/Mitf mutants.

PMID- 11955611
TI  - Up-regulation of thrombospondin-1 gene by epidermal growth factor and
      transforming growth factor beta in human cancer cells--transcriptional activation
      and messenger RNA stabilization.
AB  - Thrombospondin-1 (TSP-1), a multifunctional matrix protein, affects tumor growth
      through modulation of angiogenesis and other stromal biological functions. In
      several of nine human cancer cell lines derived from liver, brain, pancreas, and
      bone, expression of TSP-1 was up-regulated in response to the two most
      representative growth factors, epidermal growth factor (EGF) and transforming
      growth factor beta1 (TGFbeta1). Expression of TSP-1 was markedly enhanced in
      hepatic HuH-7 cells by EGF but not by TGFbeta1. In contrast, expression of TSP-1
      was markedly enhanced by TGFbeta1, but not by EGF, in osteosarcoma MG63 cells.
      EGF induced activation of TSP-1 promoter-driven luciferase activity in HuH-7
      cells, and the elements between -267 and -71 on the 5' region of TSP-1 gene
      containing two GC boxes to which Sp1 bound, were found to be responsible for the
      promoter activation by EGF. However, EGF did not alter TSP-1 mRNA stability in
      hepatic cells. On the other hand, no such enhancement of the TSP-1 promoter
      activity by TGFbeta1 appeared in MG63 cells. Enhanced expression of TSP-1 by
      TGFbeta1 in MG63 cells was partially blocked by exogenous addition of SB203580,
      an inhibitor of p38 mitogen-activated protein kinase. TGFbeta was found to induce
      marked elongation of TSP-1 mRNA longevity in osteosarcoma cells when mRNA
      degradation was assayed in the presence of alpha-amanitin. The up-regulation of
      TSP-1 by EGF and TGFbeta might play a critical role in modulation of angiogenesis
      and formation of matrices in tumor stroma.

PMID- 11955612
TI  - Functional human NAIP promoter transcription regulatory elements for the NAIP and
      PsiNAIP genes.
AB  - Neuronal apoptosis inhibitory protein (NAIP) has been shown to inhibit apoptosis
      in vitro and in vivo with an expression which is regulated in a variety of cells
      and tissues and may be modulated by a variety of external stimuli. To understand
      the molecular basis of the transcriptional regulation of the NAIP gene, we have
      analyzed the 5'-flanking region and transcription of the human NAIP gene. The
      functional promoter and silencer elements were identified by luciferase reporter
      constructs in transient transfection experiments using four different human
      cells. Although the location of the functional elements were shared among the
      different cells used, the activities for the NAIP promoter varied. Further, cell
      type-specific protein binding activities were observed by an electrophoretic
      mobility shift assay (EMSA). EMSA analysis with specific antibodies and DNA
      sequence analysis identified the POU domain transcription factor Brn-2 as a
      candidate transcriptional regulator of the NAIP gene. The DNA sequence of the
      promoter region of the PsiNAIP gene, a copy gene for NAIP, was nearly identical
      to that of the NAIP gene, indicating a common regulatory mechanism for
      transcription of the NAIP and PsiNAIP genes. Indeed, the transcript of the
      PsiNAIP gene was identified. These results provided the first evidence for the
      functional promoter and candidate transcriptional factor for the NAIP gene and
      transcription of the PsiNAIP gene.

PMID- 11955613
TI  - Analysis of the promoters for the beta-esterase genes associated with insecticide
      resistance in the mosquito Culex quinquefasciatus.
AB  - Resistance to organophosphorus (OP) insecticides in the mosquito Culex
      quinquefasciatus is primarily due to the amplification and over-expression of non
      specific esterases. Co-amplification of two esterase genes, estalpha2(1) and
      estbeta2(1), is the most common resistance genotype. In both resistant and
      susceptible mosquitoes the alpha- and beta-esterase genes are oriented in a head
      to-head arrangement, the intergenic sequences containing promoter elements for
      the divergent transcription of both esterases. Transient transfection of
      luciferase reporter gene constructs into a C. quinquefasciatus cell line was used
      to study these promoters. A control vector was constructed with the strong
      Drosophila actin 5c promoter driving expression of beta-galactosidase. The beta
      esterase promoters from both insecticide resistant and -susceptible insects were
      highly active in directing luciferase expression. Transfections with panels of
      deletions revealed several regions where binding sites for positive and negative
      regulatory elements are located, and candidate transcription factor sites have
      been identified. Gel shift assays have identified one DNA-protein interaction
      that is stronger with the resistant than with the equivalent but slightly altered
      susceptible sequence. The arthropod initiator site TCAGT 135bp upstream of the
      ATG in both beta-esterase promoters is essential for transcription initiation,
      but a putative TATA box is not involved.

PMID- 11955614
TI  - Cloning and expression analysis of the chicken DEAD box gene DDX1.
AB  - DEAD box proteins are putative RNA unwinding proteins found in organisms ranging
      from mammals to bacteria. While some DEAD box genes expressed in higher
      eukaryotes are ubiquitous, others have distribution profiles that suggest a cell
      , tissue-, or developmental-specific role. The DEAD box gene, DDX1, was
      identified by differential screening of a subtracted retinoblastoma cDNA library.
      A limited survey of human fetal tissues indicated that DDX1 mRNA has a widespread
      distribution but is not uniformly expressed in all tissues. To further document
      the spatial and temporal distribution of DDX1 during embryonic development, we
      cloned the chicken DDX1 cDNA. The predicted amino acid sequence of chicken DDX1
      was 93% identical to that of human DDX1. All DEAD box motifs, as well as a SPRY
      domain, were present in chicken DDX1. Northern and Western blot analyses showed
      highest levels of DDX1 at early stages of development. Tissue maturation was
      generally accompanied by a decrease in expression, although DDX1 levels remained
      elevated in late embryonic retina and brain. In situ hybridization of retinal
      tissue sections revealed widespread distribution of DDX1 mRNA at early
      developmental stages with preferential expression in amacrine and ganglion cells
      of the differentiated tissue. Preferential expression of DDX1 was also observed
      in specific areas of the brain in older embryos, such as the external granule
      layer of the cerebellum. These results suggest a specific role for DDX1 in
      subsets of differentiated cells as well as a more general role in
      undifferentiated cells.

PMID- 11955615
TI  - Purification and characterization of an endo-exonuclease from Podospora anserina
      mitochondria.
AB  - The senescence phenotype of Podospora anserina wild-type strains depends on
      mitochondrial (mt) genome stability. Characterization of activities implicated in
      the maintenance of the mt DNA is therefore essential for a better understanding
      of these degenerative processes. To address this question we looked for a
      nuclease activity in this fungal mitochondria. Here we describe the purification
      of an endo-exonuclease active on single-stranded, double-stranded and flap DNA.
      The Podospora nuclease also possesses an RNase H activity. Gel filtration
      chromatography showed a native molecular mass of 90 kDa for the P. anserina
      enzyme. The highly purified fraction shows a single polypeptide chain of 49 kDa
      on SDS-PAGE, indicating that the Podospora enzyme is probably active as a dimer.
      Purification and sequencing of the endolysine digestion peptides of the Podospora
      mt nuclease suggested that this enzyme could belong to the 5' structure-specific
      endo-exonuclease family. The possible involvement of this nuclease in mt DNA
      recombination during the senescence process is evoked.

PMID- 11955616
TI  - Vitamin A-related compounds, all-trans retinal and retinoic acids, selectively
      inhibit activities of mammalian replicative DNA polymerases.
AB  - Retinoic acids, vitamin A-related compounds, are known to be inhibitors of
      telomerase. We found that fucoxanthin from the sea alga Petalonia bingamiae is a
      potent inhibitor of mammalian replicative DNA polymerases (i.e., pol alpha, delta
      and epsilon). Since fucoxanthin is a carotenoid (provitamin A-related) compound,
      we characterized the biochemical modes of vitamin A-related compounds including
      vitamin A and provitamin A in this report. Subsequently, we found that
      fucoxanthin, all-trans retinal (RAL, vitamin A aldehyde) and all-trans retinoic
      acid (RA, vitamin A acid) inhibited the activities of replicative DNA polymerases
      with IC(50) values of 18-190, 14-17 and 8-30 microM, respectively. On the other
      hand, all-trans retinol (vitamin A) did not influence any of the DNA polymerase
      activities. RA inhibited not only the activities of pol alpha, delta and epsilon
      with IC(50) values of 30, 28 and 8 microM, respectively, but of pol beta with an
      IC(50) value of 27 microM. The tested vitamin A-related compounds did not
      influence the activities of DNA polymerases from a higher plant, cauliflower,
      prokaryotic DNA polymerases, or DNA metabolic enzymes such as human
      immunodeficiency virus type 1 reverse transcriptase, T7 RNA polymerase and bovine
      deoxyribonuclease I. RAL and RA should be called selective inhibitors of
      mammalian DNA polymerases including telomerase, and RAL was a specific inhibitor
      of mammalian replicative DNA polymerases. As expected from these results in
      vitro, some of them could prevent the growth of NUGC-3 human gastric cancer
      cells, and especially RAL was a potent antineoplastic agent with an LD(50) value
      of 19 microM. The cells were halted at G1 phase in the cell cycle by RAL.

PMID- 11955617
TI  - 1H NMR studies of a 17-mer DNA duplex.
AB  - Transcription factor 1 (TF1), encoded by the Bacillus subtilis bacteriophage
      SPO1, is a DNA-binding protein of the HU family. In preparation for a
      determination of the structure of the DNA-TF1 complex, we have studied the
      conformation of one core 17-mer duplex d(5'-CACTACTCTTTGTAGTG-3')-d(5'
      CACTACAAAGAGTAGTG-3'). NOESY, DQF-COSY and TOCSY spectroscopy provide resonance
      assignments of non-exchangeable and exchangeable protons, internucleotide and
      interstrand proton-proton distances, and dihedral angle constraints. Restrained
      molecular dynamics calculations yield a family of NMR solution structures for
      which the RMSD is 0.7 A (all atoms). The helical twist is 34.9 degrees for the
      central 15 bp. Bends toward the major groove are located between the second and
      fourth base pairs from each end. The G12 x C23 base pair, which is bounded on
      each side by consecutive A x T pairs, causes a local disturbance to the DNA helix
      that makes the conformations of the two end segments unsymmetrical. The
      pyrimidine rings at T9, T10 and T11 experience more extensive rotational movement
      than the rest of the structure.

PMID- 11955618
TI  - Inhibiting transcription factor/DNA complexes using fluorescent microgonotropens
      (FMGTs).
AB  - Fluorescent microgonotropens (FMGTs) are A/T selective, minor groove-binding
      bisbenzimidazole ligands. Basic side chains extending from these agents
      electrostatically contact the major groove side of the phosphodiester backbone of
      DNA, endowing them with high binding affinity. Here, we evaluate the potential of
      these agents as inhibitors of transcription factor (TF) binding to DNA and
      explore whether their ability to contact both grooves enhances their inhibitory
      activity. A series of FMGTs (L2-L5), with polyamine tails of varying lengths and
      degrees of branching, were compared to an analog lacking these basic side chains
      (L1), and the classical bisbenzimidazole Hoechst 33342 for effects on TF complex
      formation on the c-fos serum response element (SRE). Although L1 could not
      inhibit TF/SRE interactions, L2-L5 did so at submicromolar concentrations.
      Moreover, the FMGTs were up to 50 times more potent than Hoechst 33342 in
      inhibiting TF complex formation in electrophoretic mobility shift assays. The
      FMGTs also inhibited c-fos promoter-driven cell-free transcription and
      topoisomerase II activity in nuclei. These studies establish the potential of
      FMGTs as TF/DNA complex inhibitors in cell-free systems, provide insight into the
      relationship between their structure and biological activities, and demonstrate
      the benefits of functionalizing minor groove binding-agents with major groove
      contacting groups.

PMID- 11955619
TI  - Evidence for lateral transfer to Brucellae: characterization of a locus with a Tn
      like element (Tn2020).
AB  - A genomic locus was discovered within Brucella abortus that contains a novel
      transposon-like element designated Tn2020. Tn2020 is bounded by a copy of an
      insertion sequence designated IS2020 and a truncated imperfect copy of IS2020
      (tIS2020A). The truncated copy is immediately adjacent to a second copy of
      IS2020. These data are consistent with the locus having evolved by a complex
      rearrangement following the transposition of a second copy of Tn2020. Analysis of
      the organization, orientation, and open reading frames (ORFs) of IS2020 places it
      within the IS6 family. Four ORFs from Tn2020 were translated in vitro producing a
      potential transposase with an apparent molecular mass of 27.5 kDa, and three
      polypeptides with apparent molecular masses of 71 kDa, 22 kDa, and 14 kDa. The
      central region of Tn2020 encodes the 71 kDa and 14 kDa proteins, while the 22 kDa
      protein is likely an internal translation initiation product of the IS2020
      transposase. The 71 kDa protein shares sequence similarity with several bacterial
      transcriptional regulatory proteins and may form a helix-turn-helix structure
      capable of binding DNA. No homologous protein sequences to the 14 kDa peptide
      were detected in available databases. The 27.5 kDa transposase and its 22 kDa
      internal translation product shared significant similarity to several
      transposases from diverse bacterial hosts. Immediately 5' of Tn2020 are genes
      encoding ribosomal proteins RplU and RpmA. This region also contains a 90 bp
      sequence that shares significant homology to a repetitive element with inverted
      repeats from the Sinorhizobium genome. Downstream from Tn2020 is an ORF encoding
      a protein having significant similarity to a hypothetical protein from
      Caulobacter. The locus is lower in G+C content from that of the genome. These
      data suggest that lateral transfer of genetic material has occurred.

PMID- 11955620
TI  - Isolation of a genomic clone containing the promoter region of the human ATP
      binding cassette (ABC) transporter, ABCB6.
AB  - We previously reported on the isolation of a new rat ATP binding cassette (ABC)
      transporter, ABCB6. We now report the isolation of the full-length cDNA and
      genomic clones containing the human ABCB6 gene. ABCB6 is 100% identical to the
      cloned MTABC3 human ABC transporter and contains the typical ABC signature,
      Walker A and B motifs. We found that HuABCB6 is expressed at low levels in normal
      human liver. We found that ABCB6 was overexpressed in human hepatocellular
      carcinomas compared to paired surrounding non-malignant tissue. We found that
      there was no difference in ABCB6 gene copy between human liver cancer and its
      paired non-malignant tissue. Because HuABCB6 was overexpressed in human cancers
      compared to peri-tumoral tissue in the absence of gene amplification,
      transcriptional regulation may play an important role in its expression.
      Therefore, we isolated a 14 kb genomic DNA clone containing the HuABCB6 promoter
      and 5'-flanking region. The 5'-flanking region contains a CpG island, lacks an
      appropriately positioned TATA element and contains a number of putative
      transcription factor binding sites. Two transcription start sites were identified
      by S1 nuclease mapping at -274 and -296 bp from the start codon. Transient
      transfection of the HuABCB6 promoter constructs (HuABCB6/1.68, 1.39, 1.13, 0.90,
      0.52) containing the luciferase reporter gene resulted in a 1100-2300-fold
      increase in luciferase activity compared to the empty vector control whereas
      HuABCB6/1.68 subcloned in the reverse orientation resulted in no activity. We
      observed a significant decrease in luciferase activity with the promoter
      constructs, HuABCB6/0.25, 0.15 and 0.06, which indicates that an orientation
      dependent functional promoter is contained within our previously predicted
      promoter region of -315 bp to -565 bp as deletion of this 250 bp sequence
      resulted in a loss of promoter activity.

PMID- 11955621
TI  - An intronic AP-1 sequence mediates the transcriptional activation of the F-type 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase by serum.
AB  - The expression of F-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is
      rapidly induced by growth factors. We report here that an AP-1 intragenic
      sequence located at position +612 of the F-type 6-phosphofructo-2-kinase/fructose
      2,6-bisphosphatase transcription initiation site is involved in the
      transcriptional activation of this gene by serum. We have demonstrated in vitro
      DNA-protein interaction on this AP-1 site of the F-promoter. Indeed, this element
      was recognized by c-Fos and JunD in vitro, and mutation or deletion of this
      element reduced the early response to serum stimulation by 60%. We conclude that
      the serum response of the F-type 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase gene requires the co-ordinated function of ets, E2F and AP-1
      binding sites.

PMID- 11955622
TI  - Pseudouridylation of U(35) in the anticodon of Arabidopsis thaliana pre-tRNA(Tyr)
      depends on length rather than structure of an intron.
AB  - In order to establish the structure and sequence requirements for pseudouridine
      (Psi(35)) biosynthesis in Arabidopsis thaliana tRNA(Tyr) five mutants of nuclear
      pre-tRNA(Tyr) have been prepared and analyzed: DeltaI-tRNA(Tyr) transcript
      depleted of an intron, and 5UI, 7UI, 9UI and 12UI transcripts containing tracts
      of five, seven, nine and 12 U residues, respectively, instead of the wild type
      tRNA(Tyr) intron. The in vitro transcripts were incubated in a lupin seed extract
      containing Psi(35) synthase activity, and those containing an artificial intron
      composed of 12 or nine U residues turned out to be good substrates for Psi(35)
      synthase. The transcript with an intron composed of seven uridine residues was
      pseudouridylated up to 40%, whereas the remaining two were not pseudouridylated
      at all. The secondary structures of all transcripts were determined using
      enzymatic and chemical probes: S(1), V(1), T(1), A, P(1) and Pb(2+). All mutant
      pre-tRNAs show similar structural features: their anticodon arm contains a five
      base pair stem and a large loop which consists of five natural tRNA(Tyr) AC loop
      nucleotides to which five, seven, nine and 12 U residues are added. As the
      structure of the wild type pre-tRNA(Tyr) is different we propose that the role of
      its intron in the process of U(35) pseudouridylation is simply to expand the
      anticodon region to the required critical length.

PMID- 11955623
TI  - Molecular cloning and cellular expression of crustacean PC2-like prohormone
      convertase.
AB  - PC2 prohormone convertases are enzymes involved in the proteolytic maturation of
      neuropeptide precursors. In the present work, a cDNA encoding a PC2-like enzyme
      (OrlPC2) was cloned from crayfish eyestalk ganglia (medulla terminalis)
      containing the X-organ, a major neuroendocrine center. The predicted 634 amino
      acid preproprotein exhibits highest sequence identity, especially in the
      catalytic domain, with PC2s from arthropods and nematodes, and less with mollusc
      and vertebrate enzymes. It was demonstrated by in situ hybridization on crayfish
      medulla terminalis sections that OrlPC2 is expressed in a large number of neuron
      perikarya, including those producing the well known crustacean hyperglycemic
      hormone.

PMID- 11955624
TI  - Identification of an additional hypoxia responsive element in the glyceraldehyde
      3-phosphate dehydrogenase gene promoter.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme
      overexpressed in many tumors and induced by hypoxia in normal and malignant
      cells. The degree to which hypoxia transcriptionally activates GAPDH is cell type
      specific. The GAPDH promoter region contains a hypoxia responsive element (HRE)
      consisting of a hypoxia inducible factor-1 (HIF-1) consensus binding site plus
      adjacent sequence [Graven et al. (1999) Biochim. Biophys. Acta 1447, 208-218].
      Using transient transfection experiments with the GAPDH promoter region linked to
      a luciferase reporter gene, we found that GAPDH was transcriptionally activated
      by hypoxia in each of three human prostate cancer cell lines tested, with the
      greatest level of induction in the most differentiated cell line. Using sequence
      analysis of the GAPDH promoter region, we identified a novel HRE distinct from
      the previously characterized one that consists of two consensus HIF-1 sites
      arranged as inverted repeats separated by 5 bp. Hypoxia transcriptionally
      activated a promoter construct in which the previously characterized HRE was
      mutated and the novel HRE remained intact. Heterologous promoter constructs
      containing only one or two copies of the novel HRE plus a minimal promoter
      consisting of a TATA box drove hypoxia inducible expression of the luciferase
      reporter gene in transient transfection assays. Mutation of HIF-1 sites within
      the novel HRE resulted in complete loss of function.

PMID- 11955625
TI  - ik3-2, a relative to ik3-1/cables, is associated with cdk3, cdk5, and c-abl.
AB  - A cDNA coding for ik3-2 (designated as ik3-2 from an interactor-2 with cdk3) was
      cloned by cross-hybridization with ik3-1 and RT-PCR. Analysis of amino acid
      sequence indicated that ik3-2 has the C-terminal cyclin-box-like region highly
      homologous to that of ik3-1 (identity in amino acids: 78%). On the other hand,
      the remainder of ik3-2 gene is not so similar to that of ik3-1. There are several
      regions other than the C-terminal cyclin-box-like region that are conserved
      between ik3-1 and ik3-2. In vivo binding assay indicated that like ik3-1, ik3-2
      binds to cdk3, cdk5, and c-abl, although ik3-2 binds to cdk3 weakly as compared
      with ik3-1. The C-terminal cyclin-box-like region of ik3-2 (123 amino acids) is
      able to be associated with cdk5. Accordingly, ik3-2 is very similar to ik3-1
      concerning its molecular interaction with other molecules, suggesting that ik3-2
      function in the same biological field as ik3-1. Northern blot analysis indicated
      that ik3-2 is expressed ubiquitously all over tissues.

PMID- 11955626
TI  - YY1 and Sp1 activate transcription of the human NDUFS8 gene encoding the
      mitochondrial complex I TYKY subunit.
AB  - Complex I is the most complicated of the multimeric enzymes that constitute the
      mitochondrial respiratory chain. It is encoded by both mitochondrial and nuclear
      genomes. We have previously characterized the human NDUFS8 gene that encodes the
      TYKY subunit. This essential subunit is thought to participate in the electron
      transfer and proton pumping activities of complex I. Here, we have analyzed the
      transcriptional regulation of the NDUFS8 gene. Using primer extension assays, we
      have identified two transcription start sites. The basal promoter was mapped to a
      247 bp sequence upstream from the main transcription start site by reporter gene
      analysis in HeLa cells and in differentiated or non-differentiated C2C12 cells.
      Three Sp1 sites and one YY1 site were identified in this minimal promoter.
      Through gel shift analysis, all sites were shown to bind to their cognate
      transcription factors. Site-directed mutagenesis revealed that the YY1 site and
      two upstream adjacent Sp1 sites drive most of the promoter activity. This work
      represents the first promoter analysis for a complex I gene. Together with
      previous studies, our results indicate that YY1 and Sp1 control the expression of
      genes encoding proteins that are involved in almost all steps of the oxidative
      phosphorylation metabolism.

PMID- 11955627
TI  - Functional analysis of the glucose response element of the rat glucagon receptor
      gene in insulin-producing INS-1 cells.
AB  - Glucose stimulates the transcription of the glucagon receptor gene in hepatocytes
      and in pancreatic beta cells. We recently identified a glucose response element
      in the immediate upstream non-coding region of the rat glucagon receptor gene. We
      previously showed that this DNA element is centered on a palindromic sequence of
      19 nucleotides (termed as G box), containing two E boxes separated by three
      nucleotides. In the present study, we further characterized the DNA sequence
      requirements for the glucose induced expression of the rat glucagon receptor
      gene. Transfection study realized in the insulin-producing INS-1 cells revealed
      that a fragment of 49 nucleotides, centered on the G box, bears all the features
      required for the glucose activation. Mutations performed in the 5'-E box totally
      abolished the glucose responsiveness, whereas mutations or deletion of the 3'-E
      box only had a limited effect. Deletions performed upstream from the G box
      revealed that an accessory factor binding site, located in the region just
      upstream from the G box, is required for full stimulation by glucose. Finally, by
      using G box based probes in gel shift experiments, we demonstrated that USF1/USF2
      transcription factors are part of the proteinic complex that binds to the glucose
      response element of the rat glucagon receptor gene promoter. In conclusion, in
      contrast to many other glucose regulated genes, only the 5'-E box appears to be a
      crucial DNA element for the glucose transcriptional effect. However, an accessory
      factor binding site located in the region just upstream from the G box is
      required for a complete stimulation by glucose.

PMID- 11955628
TI  - Characterization of the 5' regulatory region of the human sodium-dependent
      multivitamin transporter, hSMVT.
AB  - We cloned and functionally characterized the 5' regulatory region of the human
      sodium-dependent multivitamin transporter (hSMVT) gene, a remarkably versatile
      carrier responsible for uptake of biotin, pantothenic acid and lipoate. Two
      potential transcriptional start sites were determined by 5'-RACE and found to be
      at -4603, and -4303. Two distinct promoters (P1 and P2) were identified. Both
      putative promoter sequences were TATA-less, CAAT-less, contained highly GC-rich
      sites, and had multiple putative regulatory cis-elements (e.g., AP1, AP2, C/EBP,
      SP1, NF1, and GATA). The activities of the putative promoters were confirmed
      using a firefly luciferase reporter gene assay system following transient
      transfection into three cultured human cell lines: Caco-2, HEK293, and vascular
      smooth muscle cells. The minimal region required for basal activity of the hSMVT
      promoter was also determined by generating a series of deletion constructs and
      found to be encoded by a sequence between -5846 to -5313 for P1 and between -4417
      to -4244 for P2 relative to the translation initiation codon. These results
      demonstrate the first molecular characterization of the regulatory region of this
      important human gene.

PMID- 11955629
TI  - Molecular cloning and characterization of the promoter of mouse heme-regulated
      eIF2alpha kinase.
AB  - The heme-regulated eIF2alpha kinase (HRI) phosphorylates the alpha subunit of the
      translation initiation factor 2, which plays an important role in translational
      regulation during heme deficiency. HRI is expressed mainly in erythroid cells. To
      elucidate the mechanisms that regulate the tissue-specific expression of the
      mouse HRI gene, we have cloned and characterized its 5' flanking region. Primer
      extension and 5' RACE analyses identified a major transcription initiation site
      84 nucleotides upstream from the ATG start codon. Sequence analysis of the 5'
      flanking region revealed that HRI promoter lacked a TATA element, but contained
      an initiator core element and three SP1 consensus binding motifs. Transient
      transfection analysis using luciferase reporter gene constructs containing a
      series of deletions and mutations in the 5' region identified a 159 bp sequence
      which is necessary and sufficient for basal HRI promoter activities in NIH 3T3
      and mouse erythroleukemic cells. Both the initiator and one of the SP1 binding
      sites in the 159 bp are essential for HRI promoter activity.

PMID- 11955632
TI  - A potential membrane protein involved in pre-tRNA splicing of Schizosaccharomyces
      pombe.
AB  - We had previously isolated six pre-tRNA splicing mutants of Schizosaccharomyces
      pombe named ptp1 to ptp6. To investigate the molecular mechanism of tRNA
      splicing, we cloned the ptp4(+) gene by complementation of the temperature
      sensitive growth defect. The ptp4(+) gene consists of three exons and encodes a
      putative protein of 218 amino acids with a molecular mass of 24.4 kDa. Analysis
      of the amino acid sequence reveals that the protein is a potential membrane
      protein with four membrane-spanning regions. The ptp4(+) shows significant
      similarity to the Saccharomyces cerevisiae putative protein YOR311C. Expression
      of the ptp4(+) gene in the ptp4(-) mutant restores the ability to splice tRNA.
      Northern blot analysis showed that the ptp4(+) gene is expressed in both mating
      type cells of S. pombe. These results suggest that the Ptp4(+) could be a
      component involved in tRNA splicing.

PMID- 11955631
TI  - Functional analysis of the 5'-flanking region of the human alanine:glyoxylate
      aminotransferase gene AGXT.
AB  - Primer extension of human liver poly(A)(+) RNA revealed that the main
      transcription start site of the human alanine:glyoxylate aminotransferase gene
      (AGXT) is situated near 45 bp upstream from the translation start site. Deletion
      analysis using the 1203 bp 5'-flanking region of the AGXT gene and a luciferase
      reporter suggested that the promoter sequence is most likely located 2-325 bp
      upstream from the translation start site, possibly with enhancer elements 440-700
      bp upstream. It was also suggested that the region -2 to -64 is important for the
      expression of the AGXT gene. The region -2 to -325 has two TATA boxes and some
      initiator elements.

PMID- 11955630
TI  - Characterization of the 5'-flanking region of the rat gene for mitochondrial
      transcription factor A (Tfam).
AB  - Mitochondrial transcription factor A (Tfam) is essential for the initiation of
      transcription and the replication of mitochondrial DNA (mtDNA). The 5'-upstream
      region of the rat Tfam gene was isolated from rat genomic DNA by extending the 5'
      sequence of newly identified Tfam cDNA using PCR-based Genome Walker. The
      identified rat Tfam gene showed little sequence homology with the upstream region
      of human Tfam. No typical TATA or potential nuclear respiratory factor 1 (NRF-1)
      binding site was found, whereas three potential binding sites for Sp1 and one for
      NRF-2 were present in the proximal upstream region. Transfection of the Tfam 5'
      upstream region ligated to luciferase into rat skeletal muscle L6 cells
      demonstrated that the promoter activity was 10 times higher than that of control
      vectors. Despite the absence of the NRF-1 consensus binding sequence, co
      transfection of human NRF-1 expression vector increased the Tfam promoter
      activity 2-fold. The gel mobility shift assays for NRF-1 demonstrated that NRF-1
      could bind to the proximal region of the promoter between -112 and +49. The
      addition of 50 mM glucose for 24 h increased Tfam promoter activity by up to 2
      fold, but 100 microM H(2)O(2) for 24 h repressed the activity to 40% of the
      control. From these results, the sequence presented here is that of authentic rat
      Tfam promoter and it is hoped that it will prove useful in studies of mtDNA
      transcription and replication.

PMID- 11955633
TI  - Proceedings of the 6th European Workshop on Virus Evolution and Molecular
      Epidemiology. Leuven, Belgium, 4-9 September 2000.

PMID- 11955634
TI  - Biological and serological variability, evolution and molecular epidemiology of
      Zucchini yellow mosaic virus (ZYMV, Potyvirus) with special reference to
      Caribbean islands.
AB  - Zucchini yellow mosaic virus (ZYMV, Potyvirus) emerged as an important pathogen
      of cucurbits within the last 20 years. Its origins and mechanisms for evolution
      and worldwide spread represent important questions to understand plant virus
      emergence. Sequence analysis on a 250 nucleotide fragment including the N
      terminal part of the coat protein coding region, revealed one major group of
      strains, and some highly divergent isolates from distinct origins. Within the
      major group, three subsets of strains were defined without correlation with
      geographic origin, year of collection or biological properties. ZYMV was first
      observed in Martinique and Guadeloupe in 1992 and 1994, respectively. We studied
      the evolution of ZYMV variability on both islands in the few years following the
      putative virus introduction. In Martinique, molecular divergence remained low
      even after 6 years, suggesting a lack of new introductions. Interactions between
      strains resulted in a stability of the high biological variability, while the
      serological diversity decreased and molecular divergence remained low. In
      Guadeloupe, as in Martinique in 1993, serological variability was high shortly
      after virus introduction. While the first introduction in Guadeloupe was
      independent from Martinique, the 'Martinique' type was detected in 1998,
      suggesting further introductions, maybe through viruliferous aphids or imported
      plant material.

PMID- 11955636
TI  - Characterisation of an Irish caprine lentivirus strain--SRLV phylogeny revisited.
AB  - Small ruminant lentiviruses (SRLV), i.e. caprine arthritis-encephalitis virus
      (CAEV) (which infects goats) and maedi-visna virus (MVV) (which infects sheep)
      are two closely related lentiviruses but the relationship between goat and sheep
      lentiviruses has not been clearly established. To better understand their genetic
      relationship, we reinvestigated the phylogeny of SRLV using new sequences from an
      Irish and a Norwegian strain together with sequences available from databases.
      The phylogenetic analyses were carried out on the gag, pol and env fragments
      using four methods: neighbor-joining (NJ), Fitch and Margoliash (Fitch), Fitch
      and Wagner parsimony (Pars) and maximum likelihood (ML). The tree topologies were
      consistent whether derived from any of the four methods or any of the gene
      fragments, but the phylogenetic analyses in the pol and env regions were more
      informative than in the gag region. The Tamura-Nei model with variable rates
      across sites (described by a gamma distribution) provides a more accurate
      description of SRLV evolution than simple methods. The newly described Irish
      lentivirus strain, which was isolated from a goat, was closely related to the
      lentivirus that infects sheep: MVV. The novel Norwegian CAEV strain belonged to a
      cluster specific to the CAEV strains from Norway. Together, both data confirm the
      previously reported subdivision of the different SRLV strains into six clades.
      The caprine and ovine lentivirus sequences are interspersed in phylogenetic
      trees, supporting the existence of cross-species transmission. Nevertheless, the
      transmission of an ovine lentivirus to a goat could trigger the emergence of some
      goat-adapted phylums. Our new sequences confirm the complex situation in SRLV
      phylogeny but more sequences are needed to elucidate more precisely the
      relationship between SRLV.

PMID- 11955635
TI  - Genetic and antigenic variability in bovine viral diarrhea virus (BVDV) isolates
      from Belgium.
AB  - This report describes the genetic and antigenic variability of bovine viral
      diarrhea virus strains isolated in Belgium. Part of the 5' untranslated region
      and the 5' end of the gp53 (E2) coding sequence were amplified by PCR and
      sequenced. Phylogenetic analysis showed that most field isolates segregated into
      genotypes Ib or II. Only one out of 28 field isolates belonged to genotype Ia.
      Interestingly, some type I strains were equally divergent from types Ia and Ib
      strains and clustered into additional subtypes within genotype I. Immune sera
      from young calves experimentally inoculated with field isolates first identified
      on the basis of their sequences were used in two-way neutralisation experiments.
      The results clearly differentiated type I from type II strains although some
      degree of cross-neutralisation was observed. Within type I, the new clusters
      could not be antigenically differentiated from the more prevalent type Ib strains
      or from type Ia strain NADL, suggesting that BVDV genotype I is antigenically
      homogeneous. The isolation of BVDV types I and II strains from cell lines and
      from a bovine vaccine suggest that molecular epidemiology surveillance is
      warranted for BVDV.

PMID- 11955637
TI  - Phylogenetic analysis of rhinovirus isolates collected during successive epidemic
      seasons.
AB  - Human rhinoviruses (HRV) have been shown to be the major causative agent for mild
      respiratory infections, but also associated with more serious diseases, such as
      acute otitis media and pneumonia in children, and asthma. Despite the economical
      and medical importance of HRV, little is known about the circulation and genetic
      diversity of HRV during a given season. The aim of this study was to genetically
      characterize HRV strains causing acute respiratory infections in a cohort of
      small children during a 2 years follow-up time. Genetic relationships between 61
      HRV field isolates were studied using partial genomic sequencing in the VP4/VP2
      region (420 nt) and phylogenetic analysis of these sequences. Sequences from the
      clinical isolates clustered in the two previously known phylogenetic clades, the
      designated genetic group 2 (including HRV 14) being more predominant. The maximum
      genetic variation within group 1 was 32.3% and within group 2 it was 32.7%.
      Several distinct clusters could be observed, some of which were strictly
      seasonal, whereas some other variants were detected during several seasons. The
      results of this study show striking genetic diversity of the HRV strains
      circulating in a given community during a short time.

PMID- 11955638
TI  - Phylogenetic classification of TT virus groups based on the N22 region is
      unreliable.
AB  - Evolutionary studies on the recently discovered TT virus (TTV) are currently
      focused on approximately 220 nts of the N22 region, since this is the region for
      which most sequence information is available. Regarding the extensive sequence
      heterogeneity in this region, within group classification can be sufficiently
      reliable, however, between group classification becomes problematic. We observed
      high divergence at the nucleotide level between distant related strains (TTV
      groups) preventing unambiguous alignments, saturation in transitions within TTV
      groups and considerable phylogenetic noise due to conflicting signals within
      distinct genotypes. Consequently, analysing all TTV groups in one tree, using
      this 220 nt region provides unreliable results. Also within genotype analysis can
      produce conflicting results. On the other hand, this region is still suitable to
      some extent for within TTV group phylogenetic analysis. We suggest that care
      should be taken in future TTV phylogenetic analysis, in particular, larger and
      more conserved regions should be sequenced to allow between group comparisons.

PMID- 11955639
TI  - Phylogenetic analysis of Ljungan virus and A-2 plaque virus, new members of the
      Picornaviridae.
AB  - In addition to the viruses belonging to the nine proposed genera of the
      Picornaviridae, Enterovirus, Rhinovirus, Cardiovirus, Aphtovirus, Hepatovirus,
      Parechovirus, Kobuvirus, Erbovirus and Teschovirus, two new members of this
      family have recently been discovered. Three strains of Ljungan virus (LV) were
      isolated from bank voles (Clethrionomys glareolus) and A-2 plaque virus (A-2) was
      isolated from human sera. To study the genetic relationship between these
      recently discovered viruses and the members of the family Picornaviridae, an
      evolutionary analysis has been carried out using the amino acid sequences of the
      two nonstructural proteins 2C and 3D. Phylogenetic analysis using prime members
      of the nine genera support the division of picornaviruses into the proposed
      genera. The study also supports a previous suggestion based on analysis of
      partial sequences of the structural proteins that LV is more related to the genus
      of Parechovirus than to other picornaviruses, but also shows that the three LV
      strains used in the comparison constitute a distinct monophyletic group, clearly
      separated from the parechoviruses. The analyses using the 2C and 3D sequences
      clearly showed that A-2 was related to the genera of Rhinovirus and Enterovirus,
      but it was not possible to group the A-2 with high confidence into one of the
      genera. Comparison using the VP1 protein sequences of Enterovirus and Rhinovirus
      showed that although the A-2 virus is positioned between the two genera, the
      virus is more related to the genus of Enterovirus than to Rhinovirus. Our
      analysis of the three LV strains based on the phylogenetic analysis of the 2C and
      3D proteins suggests that the strains used in this study constitute a
      monophyletic group clearly related to Parechovirus of Picornaviridae. The
      taxonomic position of the A-2 virus is presently uncertain but available data
      indicate that this virus may be classified as a member of the genus of
      Enterovirus.

PMID- 11955640
TI  - Molecular analysis of the echovirus 18 prototype: evidence of interserotypic
      recombination with echovirus 9.
AB  - Echovirus 18 (EV18) is one of the echovirus serotypes associated with human
      diseases and in particular aseptic meningitis. To facilitate studies of the
      molecular epidemiology of EV18 and the evolution of enteroviruses in general, the
      complete nucleotide (nt) sequence was determined for the echovirus 18 prototype
      strain (Metcalf, EV18M). Excluding the poly A sequence, the genome consists of
      7410 nt divided into a 740 nt 5' untranslated region (5' UTR), a 6567 nt long
      open reading frame coding for a 2189 amino acid (aa) polyprotein and a 103 nt 3'
      UTR. Molecular analysis of the EV18M genome showed a typical enterovirus-like
      organization. Phylogenetic analysis of the structural and non-structural genes
      revealed a pattern of different relationships to other echo- and
      coxsackieviruses. Similarity analysis demonstrated that the Hill strain of
      echovirus 9 is most likely the result of a previous recombination event between
      ancestors of the echovirus 9 strain Barty (5' half of the genome) and EV18M (3'
      half). Using a maximum likelihood approach, the recombination point was mapped to
      the 2C gene.

PMID- 11955641
TI  - HIV-1 subtypes and circulating recombinant forms (CRFs) in Northern Greece.
AB  - In order to understand the genetic diversity of virus isolates associated with
      the human immunodeficiency virus type one (HIV-1) epidemic in Northern Greece, 51
      specimens from HIV-1 infected individuals were classified into subtypes by
      sequence-based phylogenetic analysis of the polymerase (pol) region of the viral
      genome. Forty two (82.3%) specimens were identified as pol subtype B, three
      (5.9%) as A, and one (2%) as CRF01_AE, while the remaining five (9.8%) specimens
      appeared to be complex recombinants, belonging to the Cypriot/Greek form
      CRF04_cpx. The proportion of CRF04_cpx strains is larger than previously
      reported, suggesting that the CRF04_cpx is significantly contributing to the
      Greek HIV-1 epidemic.

PMID- 11955642
TI  - Prevalence and origin of HIV-1 group M subtypes among patients attending a
      Belgian hospital in 1999.
AB  - HIV-1 group M strains are usually subtyped based on gag and/or env gene
      sequences. In our lab, part of the pol gene sequence was available in order to
      determine the genotypic anti-HIV drug resistance profile. To estimate the
      prevalence of the different HIV-1 subtypes in patients visiting the University
      Hospitals in Leuven in 1999 and for whom a genotypic drug resistance test was
      needed, we tried to use the pol sequence for subtyping. Recombination was
      investigated by similarity plots and bootscanning and subtyping was performed by
      phylogenetic analysis. The overall region spanning the entire protease and 747
      nucleotides of the reverse transcriptase proved very suitable for subtyping,
      although there was a low phylogenetic signal at the beginning of the reverse
      transcriptase (nucleotides 0-250), as we demonstrated by likelihood mapping. Of
      the 41 samples analyzed, 21 belonged to subtype B. Of the other 20 non-B strains,
      9 belonged to subtype C, 2 to subtype D and 1 to subtype A, G, H and J,
      respectively, 3 were CRF_02 (Circulating Recombinant Form), 1 was recombinant
      with a novel breakpoint and 1 sample was untypable. Although subtype B is still
      the most prevalent subtype in Belgium, it seems to be responsible for only half
      of the infections in this study. We could also document that the prevalence of
      subtype C is high in the Belgian native patients, especially among the
      heterosexually infected population. This could possibly be an indication for an
      epidemic spread of HIV-1 subtype C in Belgium, as for one third of these
      patients, no link to an endemic region could be found. The other non-B subtypes
      and the recombinants are mainly introduced by immigrants or by Belgian citizens
      traveling abroad.

PMID- 11955643
TI  - Mutations associated with genotypic resistance to antiretroviral therapy in
      treatment naive HIV-1 infected patients in Greece.
AB  - The widespread use of antiviral drugs against HIV has increased the prevalence of
      HIV-1 resistant strains among naive individuals due to transmission of resistant
      strains. The purpose of this study was to investigate the presence of HIV-1
      strains harboring resistance mutations in naive patients in Greece. Blood samples
      were collected from 25 individuals. The DNA sequence of protease and partial
      reverse transcriptase regions (codons 41-223) were obtained by direct sequencing.
      Our results showed the absence of any primary resistance mutations in the study
      population. However, we were able to identify high prevalence of sequence
      polymorphisms at positions in reverse transcriptase region associated mainly with
      resistance to NNRTIs. Moreover, in protease region several secondary mutations
      were detected, suggesting the higher genetic variability of this region. The
      clinical significance of the polymorphisms associated with reduced susceptibility
      to NNRTIs remains to be clarified.

PMID- 11955644
TI  - CMV DNA in blood and CSF of HIV infected patients.
AB  - Cytomegalovirus (CMV) infection frequently affects the central nervous system in
      HIV infected patients. Varied clinical manifestations of CMV disease make
      virological detection of CMV essential for proper diagnosis and treatment. Thus,
      in patients in different stages of HIV-induced disease, we attempted to detect
      cell associated and free, non cell associated CMV DNA in cerebrospinal fluid
      (CSF) and in peripheral blood mononuclear cells (PBMCs). Twenty-six blood samples
      were collected from 22 patients included in the study. Nine of these blood
      samples were tested in pair with the concomitant CSF sample for the presence of
      CMV DNA by a commercial hybridization test. CMV serostatus and avidity of IgG
      antibodies were detected by a commercial ELISA test. CMV DNA was present in the
      cells found in CSF in all but one of the AIDS patients, independently of the
      presence of neurological symptoms, suggesting that it represented a marker of
      advanced immunodeficiency, rather than of the specific CMV-related disease. Cell
      associated CMV DNA in CSF tested positive even in the samples negative for cell
      free CMV DNA in the CSF, and with no detectable CMV DNA in the PBMCs of
      concomitant blood sample. We believe that searching for CMV DNA in different
      compartments of CSF merits further attention.

PMID- 11955645
TI  - The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastasis,
      and prognosis.
AB  - BACKGROUND: Lung cancer is the most common cause of cancer deaths in the western
      world. Progress in treatment results has been limited, and the prognosis is poor
      with a 5-year survival less than 15%. Based on new developments in molecular
      biology, our knowledge about lung carcinogenesis and mechanisms for invasion and
      metastasis has expanded and may in the future lead to more specific targeted
      therapies and better prognosis. The E-cadherin-catenin complex is critical for
      intercellular adhesiveness and maintenance of normal and malignant tissue
      architecture. Reduced expression of this complex in malignant disease is
      associated with tumour invasion, metastasis, and unfavorable prognosis. METHODS:
      This review is based on search in the Medline database from 1991 to 2001. We have
      reviewed the relevance of the E-cadherin-catenin adhesion complex in malignancy
      in general and lung cancer in particular. Furthermore, its role as target for
      specific therapy is discussed. RESULTS: Available data indicate that alterations
      of proteins involved in the E-cadherin-catenin complex are early incidents in
      cancer development. Reduced or altered expression of one or more of the
      components in this complex is associated with extended invasive and progressive
      behavior of cancer cells. Consistently, the E-cadherin-catenin complex appears to
      be increasingly delicate with regard to cancer prognosis. beta-Catenin, one of
      the components of the adhesion complex, also plays a significant role in cell
      signal transduction, gene activation, apoptosis inhibition, and increased
      cellular proliferation and migration. CONCLUSION: Inactivation of the E-cadherin
      catenin adhesion complex, induced by genetic and epigenetic events, plays a
      significant role in multistage carcinogenesis, and seems to be associated with
      dedifferentiation, local invasion, regional metastasis, and reduced survival in
      lung cancer.

PMID- 11955646
TI  - Association of L-myc polymorphism with lung cancer susceptibility and prognosis
      in relation to age-selected controls and stratified cases.
AB  - The association of L-myc polymorphism with cancer susceptibility and prognosis
      has produced conflicting results. This may have been due to racial/ethnic
      differences and methodological variations in the studies, such as, control
      selection and case stratification. Therefore, we investigated the genotype
      distribution of the L-myc polymorphism in 169 lung cancer patients and 169 non
      cancer controls, and analyzed the association of this polymorphism with cancer
      susceptibility and prognosis in relation to age-specific controls as well as
      stratified cases. The genotype frequencies in the Taiwanese non-cancer controls
      were 0.56 (L) and 0.44 (S). Chi-square (chi(2)) analysis indicated a significant
      difference in the Taiwanese genotype distribution of L-myc compared with that of
      African-Americans (P=0.001). Logistic regression analysis of cases/controls,
      adjusted for both age and sex, indicated that an increased frequency of the LL
      genotype was observed in early-staged patients compared with the non-cancer
      controls (OR=0.43, 95% CI, 0.20-0.94, P=0.03). In addition, the frequency of the
      LL genotype was significantly higher in stages I+II patients (47.4%) than in
      stages III+IV patients (28.4%) (P=0.05). Furthermore, the S allele frequency was
      significantly increased in stages III+IV patients (P=0.005). As both L-myc and
      p53 polymorphisms were analyzed for their prognostic value, the patients with an
      S allele of the L-myc gene and a Pro/Pro variant genotype of the p53 gene had
      significantly poorer prognoses compared with other patients (P=0.004, by the log
      rank test). These data suggest that the S allele of the L-myc polymorphism may be
      associated with lung cancer progression.

PMID- 11955648
TI  - Reduced expression of thrombospondin-1 correlates with a poor prognosis in
      patients with non-small cell lung cancer.
AB  - Thorombospondin-1 (TSP-1) is a 450 kDa extracellular matrix glycoprotein, with
      anti-angiogenic activity. We analyzed the relationship in TSP-1 expression and
      Microvessel count (MVC), and also clinical factors, using immunohistochemical
      methods for non-small cell cancer (NSCLC). Histopathologically, there was inverse
      correlation between TSP-1 expression and MVC for squamous cell carcinoma, but not
      for adenocarcinoma cases. Among 199 completely resected cases of NSCLC, the 5
      year survival was 77.0% when the expression of TSP-1 was maintained and 55.1%
      when the expression were reduced, respectively (P=0.0046). When compared with TSP
      1 expression in the high MVC subgroup, there was significantly shorter survival
      time when TSP-1 expression was reduced (P=0.0091), and no significant difference
      was seen for the low MVC subgroup. Multivariate analysis revealed that expression
      of TSP-1 is as a prognostic factor of NSCLC. Our present data suggest that TSP-1
      might not be a direct anti-angiogenic factor and the TSP-1 expression is a
      prognostic indicator of NSCLC.

PMID- 11955647
TI  - Differential expression and biodistribution of cytokeratin 18 and desmoplakins in
      non-small cell lung carcinoma subtypes.
AB  - Adenocarcinoma (AC), squamous cell carcinoma (SCC) and adenosquamous carcinoma
      (ASC) of the lung are morphologically distinguished in part by cyto-architectural
      features. However, little is known about the relative expression and distribution
      of cyto-architectural proteins among AC, SCC and ASC. Initial microarray analysis
      revealed significant differences in expression of two cyto-architectural genes in
      AC, SCC and ASC. Desmoplakin (DP) 1 and 2, which link desmosomes to intermediate
      filaments, was strongly expressed in SCC relative to AC and ASC. Cytokeratin 18
      (CK18), an intermediate filament that is commonly linked to desmoplakin, was
      strongly expressed in AC and ASC relative to SCC. Western blot analysis
      demonstrated that AC and ASC had abundant CK18 protein, whereas CK18 was weakly
      detected in SCC. DP 1 and 2 are strongly expressed in SCC and minimally expressed
      in AC and ASC. However, the ratio of one to the other is the same in SCC and AC,
      but DP2 is lost in ASC. Microscopic analysis with fluorescence-labeled antibodies
      for CK18 and DP 1 and 2 revealed abundant membrane localization of DP and minimal
      perinuclear localization of CK18 in SCC. In contrast, in both AC and ASC, the
      CK18 protein was diffusely distributed within the cytoplasm, and DP showed both
      membranous and cytoplasmic localization. In conclusion, the data here shows that
      AC, SCC and ASC each have specific patterns of DP 1 and 2 and CK18 gene
      expression, protein content and biodistribution.

PMID- 11955649
TI  - Functional detection of epithelial cell adhesion molecule specific cytotoxic T
      lymphocytes in patients with lung cancer, colorectal cancer and in healthy
      donors.
AB  - Epithelial cell adhesion molecule (Ep-CAM) derived antigenic peptides have been
      identified that can be recognized by cytotoxic T lymphocytes (CTL) in a major
      histocompatibility complex (MHC) class I restricted fashion. Thus, altered
      expression of Ep-CAM in a variety of human tumors might render a potential target
      for T cell mediated therapy. We have examined, whether the novel HLA-A*0201
      restricted peptide ILYENNVIT (184-192) corresponding to Ep-CAM and one
      heteroclitic modified variant peptide previously demonstrated to be immunogenic
      in the human system can elicit antigen specific CTL responses in HLA-A2 positive
      patients with history of Ep-CAM expressing cancer of lung and colon. Specific CTL
      recognition of T2 target cells pulsed with the native peptide as well as of the
      lung cancer cell line A549 indicates that an appropriate T cell repertoire can be
      expanded from peripheral blood from patients in clinical remission and with
      advanced cancer. Despite an overall low frequency, peptide specific precursor
      CTLs could be readily expanded from peripheral blood from 6/8 patients that were
      diagnosed previously with Ep-CAM expressing lung cancer and 4/8 control
      individuals (2/5 healthy donors and 2/3 colon cancer patients). CTLs from three
      of five lung cancer patients tested also lyzed the HLA-A2(+) and Ep-CAM
      expressing lung cancer cell line A549. We did not detect an increased frequency
      of pCTLs after peripheral blood monocytes (PBMCs) were stimulated with the
      heteroclitic compound peptide. The results of our study indicate that Ep-CAM
      specific precursor CTL can be expanded in vitro and a specific T cell response
      against this epitope can be elicited in patients at various stages of lung
      cancer.

PMID- 11955650
TI  - The predictive value of neuroendocrine markers and p53 for response to
      chemotherapy and survival in patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: A minority of patients (30-40%) with advanced non-small cell lung
      cancer (NSCLC) have objective responses to chemotherapy. Therefore, defining
      molecular features that determine resistance or response to chemotherapy would
      have important implications in this disease. Several studies have suggested that
      patients whose tumors have neuroendocrine features may be more responsive to
      chemotherapy. In addition, increased expression of p53 may play a role in
      chemotherapy resistance in patients with NSCLC. METHODS: The objective of this
      study was to analyze retrospectively, the correlation between marker expression
      and response to chemotherapy and survival using immunohistochemistry for
      neuroendocrine markers and p53. Ninety patients with unresectable stage III or IV
      NSCLC, treated with platinum based combination chemotherapy were evaluated. The
      pathological specimens were obtained prior to chemotherapy. RESULTS: There was no
      statistically significant correlation between any individual marker and response
      to chemotherapy. However, patients with tumors with increased expression of p53
      were more likely to have progressive disease following chemotherapy (P=0.02).
      Similarly, patients with tumors lacking neuroendocrine expression and with
      increased expression of p53 were more likely to have progressive disease when
      compared to patients with tumors with normal p53 expression and neuroendocrine
      differentiation (P=0.03). Normal expression of p53 along with the presence of
      neuroendocrine differentiation was a favorable factor for both survival (P=0.05)
      and time to disease progression (P=0.04) in the multivariate analysis.
      CONCLUSION: The presence of neuroendocrine markers alone was not predictive of
      response to chemotherapy and did not impact on the survival of this group of
      patients with advanced stage NSCLC. The normal expression of p53 together with
      neuroendocrine differentiation seems to impact favorably on overall survival time
      and time to disease progression without significant improvement in response to
      chemotherapy.

PMID- 11955651
TI  - Accelerated hyperfractionated radiation, concurrent paclitaxel/cisplatin
      chemotherapy and surgery for stage III non-small cell lung cancer.
AB  - The low surgical cure rate in patients with stage III non-small cell lung cancer
      has prompted an exploration of multimodality treatment strategies. Mature results
      are presented from a phase II trial of accelerated hyperfractionated radiation
      therapy, concurrent paclitaxel/cisplatin chemotherapy and surgery for these
      patients. Between 1994 and 1997, 45 patients with surgically demonstrated stage
      III non-small cell lung cancer underwent induction treatment with a 96 h
      continuous cisplatin infusion (20 mg/m(2) per day) and a 24 h infusion of
      paclitaxel (175 mg/m(2)) given concurrently with accelerated hyperfractionated
      radiation therapy (1.5 Gy twice daily) to a total dose of 30 Gy. Induction was
      completed in ten treatment (12 total) days. Surgical resection was scheduled 4
      weeks later with a second identical course of chemoradiotherapy given 4-6 weeks
      post-operatively, to a total radiation dose of 60-63 Gy. Thirty-five patients had
      stage III(A) disease and ten had stage III(B) disease (eight with N(3) tumors).
      Induction toxicity included nausea in 89%, dysphagia in 89%, and neutropenia
      <1000/mm(3) in 84% which required hospitalization for fever in 40%. There were no
      toxic deaths during induction. About 40 of the 45 patients (89%) were operable
      and 32 (71%) were resectable for cure. A pathologic response was identified in 22
      patients (49%); five patients (11%) had no residual disease. Fourteen patients
      (31%) were downstaged to mediastinal node negativity. With a median follow-up of
      60 months, the Kaplan-Meier projected 5-year overall survival was 29%;
      locoregional control 79%; and distant metastatic disease control 38%. The
      projected 5-year survival for the 14 patients downstaged to mediastinal node
      negativity was 50%. For the 19 patients with residual ipsilateral mediastinal
      node involvement at surgery it was 32%. This short-course of paclitaxel and
      cisplatin chemotherapy and concurrent accelerated fractionation radiation is
      tolerable despite significant myelosuppression. Locoregional control is excellent
      and survival is better than historical expectations. Patients downstaged to
      mediastinal node negativity have a prognosis similar to those with de novo stage
      I(B) and II disease. Distant metastases are the major cause of treatment failure.

PMID- 11955652
TI  - Discrimination of subtypes of small adenocarcinoma in the lung with thin-section
      CT.
AB  - We studied the usefulness of thin-section CT in discriminating two categories of
      adenocarcinoma in the lung. Thin-section CT findings, such as, lesion size,
      ground-glass opacity (GGO) areas of lesion and presence or absence of lobulation,
      coarse spiculation, air bronchogram, small air space, or pleural tag of lesion in
      62 consecutive patients with 62 adenocarcinomas (35 type A or B tumors (Noguchi's
      classification) and 27 type C tumors) of < or =20 mm, including 36 women and 26
      men with a mean age of 64 years were analyzed. We performed stepwise logistic
      modeling using all the CT findings as independent variables to estimate the
      significant factors for discriminating type C from type A or B tumor. Lesion size
      in type C tumors was significantly (P<0.001) greater than that in type A or B
      tumors. GGO areas in type C tumors were significantly (P<0.001) smaller than that
      in type A or B tumors. The prevalence of coarse spiculation, air bronchogram, and
      pleural tag in type C tumors was significantly greater (P=0.001, 0.010, and
      <0.001, respectively) than that in type A or B tumors. Logistic modeling revealed
      that the GGO area was the only significant factor for discriminating two
      categories (P<0.001). Using the percentage of GGO areas for predicting type C
      tumor, 40% or less showed the highest accuracy of 85% with 70% sensitivity and
      97% specificity. GGO areas of 30% or less had no false-positive diagnosis (100%
      specificity) with 81% accuracy but its sensitivity was low (56%). Thin-section CT
      was useful in discriminating two categories of adenocarcinoma in the lung.

PMID- 11955653
TI  - Phase I dose-escalating study of raltitrexed ('Tomudex') and cisplatin in
      metastatic non-small cell lung cancer.
AB  - BACKGROUND: The aim of this Phase I, dose-escalation study was to determine the
      maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicity
      (DLT) of a raltitrexed ('Tomudex') and cisplatin combination in patients with
      previously untreated, metastatic non-small cell lung cancer (NSCLC). PATIENTS AND
      METHODS: Patients received raltitrexed (15-min intravenous infusion), followed by
      cisplatin (1-h intravenous infusion), every 3 weeks at escalating dose levels.
      RESULTS: In total, 21 patients entered the study. No DLT was observed up to dose
      level 4 (raltitrexed 3.0 mg/m(2) plus cisplatin 80 mg/m(2)), or in the first 3
      patients who received dose level 5 (raltitrexed 3.5 mg/m(2) plus cisplatin 80
      mg/m(2)). However, 1 patient, entered at dose level 6 (raltitrexed 4.0 mg/m(2)
      plus cisplatin 80 mg/m(2)) experienced severe toxicity (including grade 3
      diarrhea), and no further patients were recruited at this level. Of 4 additional
      patients who received raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2), 3 also
      experienced DLTs. The most common adverse events included nausea/vomiting,
      asthenia, diarrhea, and hematologic toxicities. Of 19 patients evaluated for
      response, 3 achieved a partial response, 13 had stable disease, and 3 progressed.
      CONCLUSIONS: The MTD is raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2), and
      the RD for future studies is raltitrexed 3.0 mg/m(2) plus cisplatin 80 mg/m(2);
      DLTs were diarrhea and asthenia. The combination of raltitrexed and cisplatin
      shows clinical activity in patients with metastatic NSCLC.

PMID- 11955654
TI  - Phase I trial of gemcitabine and carboplatin in metastatic non-small-cell lung
      cancer: a Groupe Francais de Pneumo-Cancerologie Study.
AB  - BACKGROUND: The purpose of this study was to determine the maximum-tolerated dose
      (MTD) and the dose-limiting toxicity (DLT) of the 21 days carboplatin plus
      gemcitabine regimen in previously untreated patients with stage IV non small-cell
      lung cancer (NSCLC). METHODS: At least three patients were entered at each dose
      level. The starting dose was carboplatin AUC 4 mg/ml per min (Area Under the
      Curve; Calvert formula) on day 1 and gemcitabine 750 mg/m(2) on days 1 and 8.
      Carboplatin was increased to AUC 5 (level 3, 4) then to AUC 6 (level 5-7).
      Gemcitabine was increased to 875 (level 2, 3), 1000 (level 4, 5), 1250 (level 6)
      and finally 1500 mg/m(2) (level 7). Twenty-nine patients were entered into this
      phase I study. RESULTS: At dose level 6, a DLT (grade 4 thrombocytopenia) was
      observed in one out of six patients. At dose level 7, no DLT was observed during
      the first course, so the MTD was not reached. During the second course, two out
      of four patients presented grade 4 thrombocytopenia. None of the five patients
      receiving two courses at level 6 presented a DLT, so this level was retained for
      further phase II studies. Of the 25 patients assessable for response, five
      achieved partial responses with a response rate of 20% (95% CI, 7 to 41%). The
      median survival time was 7 months and the 1-year survival rate was 24% (95% CI, 9
      to 45%). CONCLUSION: The combination of carboplatin given on day 1 and
      gemcitabine given on days 1 and 8 every 3 weeks seems to be an acceptable
      regimen. The DLT consists exclusively of severe thrombocytopenia. Despite the MTD
      was not reached with carboplatin AUC 6 mg/ml per min and gemcitabine 1500
      mg/m(2), the recommended dose for further phase II studies is carboplatin AUC 6
      mg/ml per min and gemcitabine 1250 mg/m(2).

PMID- 11955655
TI  - Fast-growing squamous cell lung cancer.
AB  - We here report a case of squamous cell carcinoma of the lung, with an unusually
      fast tumor growth rate, so fast that its early detection was impossible even with
      two sequential chest roentgenograms taken only 36 days apart. Literature related
      to the concept of cell growth kinetics was reviewed, and the tumor volume
      doubling time that characterizes any measurable tumor was calculated for our case
      accordingly, based on the single lesion found on the plain chest film, with the
      best possible estimation of its volume. We concluded that, to the best of our
      knowledge, a squamous cell carcinoma of the lung that grew so fast (with a tumor
      doubling time less than 7.5 days) has not yet been reported to date; neither has
      a bronchogenic carcinoma of any cell type been reported with such a presentation.
      Given that a patient aged 81 belonged to a group usually with slower growth in
      tumor cell kinetics, the behavior of his tumor was indeed uncommon.

PMID- 11955656
TI  - Vasculitis due to gemcitabine.
AB  - We report the first occurrence of gemcitabine-induced vasculitis. It concerns a
      45-year-old man diagnosed with non-small lung cancer since 2 months. After the
      first cycle of chemotherapy, consisting of gemcitabine and cisplatin, he
      developed myalgia and swelling of arms and legs with impairment of movement. This
      re-occurred during the second cycle of chemotherapy. Further anemia, elevated ESR
      and increased creatininephosphokinase. A surgical biopsy showed leucocytoclastic
      vasculitis and necrosis of muscle tissue. The chemotherapy was stopped and the
      complaints disappeared and did not return.

PMID- 11955658
TI  - Pulmonary veno-occlusive disease after neoadjuvant mitomycin chemotherapy and
      surgery for lung carcinoma.
AB  - Pulmonary veno-occlusive disease (PVOD), an uncommon cause of pulmonary
      hypertension (PH) has been reported following treatment of a variety of different
      malignancies with various chemotherapy. We report here the cases of two patients
      with non-small cell lung cancer (NSCLC) who developed fatal PH after combined
      treatment with surgery and a mitomycin containing perioperative chemotherapy
      (PCT). PVOD was documented at autopsy in one patient and was strongly suspected
      in the other patient who had an identical clinical presentation and in whom the
      work-up looking for another cause of PH was negative. Mitomycin was incriminated
      in both cases. Without questioning the potential interest of perioperative
      chemotherapy in resectable NSCLC, these observations illustrate the risks related
      to the combination of pneumotoxic chemotherapy and thoracic surgery.

PMID- 11955657
TI  - Unexpected response of a pulmonary blastoma on radiotherapy: a case report and
      review of the literature.
AB  - Pulmonary blastoma (PB) is a rare malignant tumor of the lung. Treatment is
      primarily surgical, although, combination chemotherapy has been reported to
      result in objective responses in inoperable tumors or after incomplete
      resections. To our knowledge, this is the first report of a very radiosensitive
      PB, which showed major tumor reduction after several fractions of radiotherapy
      without further tumor regression after additional chemotherapy with cisplatin and
      etoposide. The literature on the treatment of PB is reviewed.

PMID- 11955660
TI  - Morbidity after induction therapy and surgery in non small cell lung cancer
      (NSCLC). Focus on pulmonary function.

PMID- 11955659
TI  - Is long term gemcitabine useful in small cell lung cancer?

PMID- 11955661
TI  - Report from the first meeting of the 'European Network on Translational Research
      in Lung Cancer Amsterdam-Barcelona-Bialystok-Heidelberg'. Thoraxklinik
      Heidelberg, Germany, July 25, 2001.

PMID- 11955662
TI  - Dietary exposures to mineral hydrocarbons from food-use applications in the
      United States.
AB  - Food-use applications of mineral hydrocarbons (MHC) derived from petroleum
      sources result in dietary exposure to these compounds by consumers. Food
      applications of MHC, including white mineral oils, paraffin waxes,
      microcrystalline waxes and petrolatum, include both direct-additive uses in which
      the MHC is intentionally applied to the food and indirect-additive uses in which
      the MHC become components of the food due to migration from food-contact
      surfaces. A key consideration in evaluating the safety of these uses of MHC is
      the level of exposure that results. We estimated exposures to MHC in the US from
      food applications based primarily on a food-consumption approach, in which MHC
      concentrations in foods were multiplied by the amount of these foods consumed.
      This was a conservative estimate, because it assumes that all foods that might
      contain MHC in fact do so at maximum possible concentrations. A "poundage
      approach", in which the amount of MHC used in food applications was divided by
      the US population to determine maximum potential per capita exposures, was used
      to validate the consumption-based estimates. Exposures to MHC from food-packaging
      applications were estimated using the FDA's food-factor approach, which takes
      into account the volume and kinds of food packaged with specific types of
      materials. A conservative estimate of mean exposure to all MHC types combined is
      0.875 mg/kg BW/day. Half of this, 0.427 mg/kg BW/day, is white mineral oils used
      as pan-release lubricants in baking, for de-dusting of stored grain, in
      confectioneries, and in coatings for fruits and vegetables. Nearly all of the
      remainder, 0.404 mg/kg BW/day, is petrolatum, primarily from its use as trough
      grease in bakery applications. Exposure to paraffin and microcrystalline waxes
      combined is only 0.044 mg/kg BW/day.

PMID- 11955663
TI  - Non-animal testing strategies for assessment of the skin corrosion and skin
      irritation potential of ingredients and finished products.
AB  - The dermatotoxicologist today is faced with a dilemma. Protection of workers and
      consumers from skin toxicities (irritation and allergy) associated with exposure
      to products, and the ingredients they contain, requires toxicological skin
      testing prior to manufacture, transport, or marketing. Testing for skin corrosion
      or irritation has traditionally been conducted in animals, particularly in
      rabbits via the long established Draize test method. However, this procedure,
      among others, has been subject to criticism, both for its limited predictive
      capacity for human toxicity, as well as for its use of animals. In fact,
      legislation is pending in the European Union which would ban the sale of cosmetic
      products, the ingredients of which have been tested in animals. These
      considerations, and advancements in both in vitro skin biology and clinical
      testing, have helped drive an intensive effort among skin scientists to develop
      alternative test methods based either on in vitro test systems (e.g. using rat,
      pig or human skin ex vivo, or reconstructed human skin models) or ethical
      clinical approaches (human volunteer studies). Tools are now in place today to
      enable a thorough skin corrosion and irritation assessment of new ingredients and
      products without the need to test in animals. Herein, we describe general testing
      strategies and new test methods for the assessment of skin corrosion and
      irritation. The methods described, and utilized within industry today, provide a
      framework for the practicing toxicologist to support new product development
      initiatives through the use of reliable skin safety testing and risk assessment
      tools and strategies.

PMID- 11955664
TI  - Local lymph node assay - validation, conduct and use in practice.
AB  - The validation of alternative methods is a relatively new activity in toxicology.
      The local lymph node assay (LLNA), a novel method for the identification of
      chemicals that have the potential to cause skin sensitization, was the first test
      to pass through the formal regulatory validation process established in the USA
      under the auspices of ICCVAM, the Interagency Coordinating Committee on the
      Validation of Alternative Methods. ICCVAM approved the LLNA as an alternative to
      guinea pig tests for the identification of skin sensitisation hazards. In this
      report, we explore the nine recommendations made by ICCVAM and discuss their
      interpretation in relation to the new OECD Guideline 429, which describes the
      LLNA. In particular, the value and limitations of the use of statistical
      evaluation of data and of the inclusion of routine positive controls is examined.
      It is concluded that the OECD Guideline as currently written embodies the
      necessary flexibility to permit conduct of the LLNA in a manner necessary to meet
      the varying needs of regulatory agencies and toxicologists around the world.

PMID- 11955665
TI  - Safety evaluation of proanthocyanidin-rich extract from grape seeds.
AB  - Proanthocyanidins, extracted from grape seeds, are widely used mainly as
      nutritional supplements. However, there has not been a systematic report to
      investigate toxicological studies on proanthocyanidins, especially in oral
      administration. In our studies, proanthocyanidin-rich extract from grape seeds
      was subjected to a series of toxicological tests to document its safety for use
      in various foods. The grape seed extract (GSE) was examined for acute and
      subchronic oral toxicity using Fischer 344 rats and for mutagenic potential by
      the reverse mutation test using Salmonella typhimurium, the chromosomal
      aberration test using CHL cells, and the micronucleus test using ddY mice. No
      evidence of acute oral toxicity at dosages of 2 and 4 g/kg, and no evidence of
      mutagenicity in the above tests was found. Administration of GSE as a dietary
      admixture at levels of 0.02, 0.2 and 2% (w/w) to the rats for 90 days did not
      induce noticeable signs of toxicity. The no-observed-adverse-effect level (NOAEL)
      of GSE in the subchronic toxicity study was 2% in the diet (equal to 1410 mg/kg
      body weight/day in males and 1501 mg/kg body weight/day in females). The results
      of our studies indicate a lack of toxicity and support the use of
      proanthocyanidin-rich extract from grape seeds for various foods.

PMID- 11955666
TI  - In vitro investigation of cytochrome P450-mediated metabolism of dietary
      flavonoids.
AB  - Human and mouse liver microsomes and membranes isolated from Escherichia coli,
      which expressed cytochrome P450 (CYP) 1A2, 3A4, 2C9 or 2D6, were used to
      investigate CYP-mediated metabolism of five selected dietary flavonoids. In human
      and mouse liver microsomes kaempferol, apigenin and naringenin were hydroxylated
      at the 3'-position to yield their corresponding analogs quercetin, luteolin and
      eriodictyol, whereas hesperetin and tamarixetin were demethylated at the 4'
      position to yield eriodictyol and quercetin, respectively. Microsomal flavonoid
      metabolism was potently inhibited by the CYP1A2 inhibitors, fluvoxamine and 
      naphthoflavone. Recombinant CYP1A2 was capable of metabolizing all five
      investigated flavonoids. CYP3A4 recombinant protein did not catalyze hesperetin
      demethylation, but showed similar metabolic profiles for the remaining compounds,
      as did human microsomes and recombinant CYP1A2, although the reaction rates in
      general were lower as compared to CYP1A2. CYP2C9 catalyzed the 4'-demethylation
      of tamarixetin, whereas CYP2D6 did not seem to play any role in the metabolism of
      the selected flavonoids. The major involvement in flavonoid metabolism of human
      CYP1A2, which mediates the formation of metabolites with different biochemical
      properties as compared to the parent compound and furthermore is known to be
      expressed very differently among individuals, raises the important question of
      whether individual differences in the CYP enzyme activity might affect the
      beneficial outcome of dietary flavonoids, rendering some individuals more or less
      refractory to the health-promoting potential of dietary flavonoids.

PMID- 11955667
TI  - Genetic toxicity of a standardized mixture of citrus polymethoxylated flavones.
AB  - Flavonoids are a ubiquitous family of phytochemicals that display a variety of
      biological effects, both beneficial and adverse depending on the individual
      compound. Certain flavonoids are genotoxic while others inhibit the genotoxicity
      of other mutagens. In the present studies, the mutagenicity of a mixture of
      polymethoxylated flavones (PMFs) purified from citrus peel oil was evaluated. The
      mixture consisted of nobiletin (32.5%), 3,3',4',5,6,7,8-heptamethoxyflavone
      (25.0%), tangeretin (14.0%), trimethylscutellarein (9.1%), sinensetin (3.9%), 5
      demethyl-nobiletin (2.8%), hexa-O-methylquercetagetin (3.3%), 5-demethyl
      tetramethylscutellarein (0.7%), 5-hydroxy-3,3',4',6,7,8-hexamethoxyflavone
      (0.7%), and a small quantity of unidentified flavonoid compounds (3.9%). In vitro
      addition of the PMF mixture over a concentration range that spanned four log
      doses (0.0005-5.0 mg/plate) did not reveal any evidence of mutagenicity in five
      bacterial tester strains (Salmonella typhimurium TA98, TA100, TA102, TA1535 and
      TA1537) either in the absence or presence of S9 activation. The PMF mixture
      exhibited a statistically significant increase in mutagenicity of L5178Y tk(+/-)
      mouse lymphoma cells at 0.05 (38.5 x 10(-6); P<0.05) and 0.1 mg/ml (61 x 10(-6);
      P<0.01) compared with vehicle-treated controls (mutation frequency=19.7 x 10(
      6)). However, these responses were within historical values observed in negative
      control cultures and extremely small compared to the positive control (EMS 0.5
      microl/ml; 1685.3 x 10(-6)). Furthermore, in the presence of S9 there was no
      indication of genetic toxicity in L5178Y tk(+/-) cells. These results demonstrate
      that the PMF mixture is not genotoxic in in vitro assay systems.

PMID- 11955668
TI  - Immunogenic properties of rapidly digested food proteins following gavage
      exposure of mice: a comparison of ovalbumin with a potato acid phosphatase
      preparation.
AB  - The ability of food proteins to resist digestion in simulated gastric fluid (SGF)
      correlates with allergenic potential. The purpose of the current investigations
      was to determine whether this association is due solely to the failure of
      unstable proteins to elicit an immune response when administered orally. We have
      examined immune responses induced in BALB/c mice by gavage administration of
      ovalbumin (OVA) and a crude potato protein extract (PPE) containing acid
      phosphatase activity. The stability of OVA and PPE in SGF was measured using
      sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The ability of
      these proteins to stimulate specific IgG and IgE antibody production in mice
      following parenteral (intraperitoneal; ip) or oral (gavage) exposure was compared
      using enzyme-linked immunosorbent and homologous passive cutaneous anaphylaxis
      assays, respectively. Both OVA and PPE induced specific IgG antibody responses
      when administered either by gavage or by ip injection. Parenteral, but not
      gavage, exposure to OVA was associated with robust IgE antibody responses.
      Administration of PPE failed to stimulate strong IgE production via either route
      of exposure. Differential stability in SGF was observed, with PPE being digested
      extremely rapidly (within 1 min), whereas OVA was more resistant. The strong
      association reported by others between stability in SGF and allergenic potential
      is unlikely to be solely due to orally-ingested labile proteins failing to
      provoke immune responses due to degradation in the stomach.

PMID- 11955670
TI  - Comparison of the oestrogenic effects of infant milk formulae, oestradiol and the
      phytoestrogen coumestrol delivered continuously in the drinking water to
      ovariectomised mice.
AB  - The potential oestrogenic effects of infant milk formulae, coumestrol and
      oestradiol delivered in the drinking water were investigated in ovariectomised
      mice. None of the infant formulae tested (three soya, two cow's milk) produced
      any uterotrophic or mitotic responses in the reproductive tract, although the
      soya milks displayed weak oestrogenic activity in vitro. Studies of the
      interactions between coumestrol and oestradiol were undertaken to investigate
      claims that phytoestrogens may act as oestrogen antagonists. The responses to
      coumestrol (100 g/ml drinking water) and 17-oestradiol (100 ng/ml) given
      separately were similar. Combined administration begun simultaneously produced
      only additive effects on uterine weight and cell proliferation in the vagina and
      uterus. While pretreatment with coumestrol for 24 h reduced the mitotic response
      of the uterus 48 h after placement of an oestradiol implant, the uterine weight
      increase was unaffected and the apparent reduction in mitoses reflected the
      natural fluctuations in the underlying cycle of cell proliferation. These studies
      indicate that coumestrol acts as a typical oestrogen and shows only additive
      effects with oestradiol. The results also indicate that infant soya milk formulae
      do not constitute a large enough source of oestrogenic compounds to invoke
      oestrogenic effects in the reproductive tract of mature mice.

PMID- 11955669
TI  - In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide
      induced rat hepatotoxicity.
AB  - Increasing evidence regarding free-radical generating agents and the inflammatory
      process suggests that accumulation of reactive oxygen species (ROS) can involve
      hepatotoxicity. Previously, we found that protocatechuic acid (PCA), a
      polyphenolic compound from Hibiscus sabdariffa L. possessing free radical
      scavenging capacity, protected against oxidative damage induced by tert
      butylhydroperoxide (t-BHP) in rat primary hepatocytes. In this study, first PCA
      was evaluated by its capacity of inhibiting xanthine oxidase (XO) and
      lipoxygenase (LO) activity in vitro, then it was used to induce hepatotoxicity to
      assess the antioxidant and anti-inflammatory bioactivity of PCA in vivo. Our
      investigation showed that pretreatment with PCA (50-100 mg/kg) by gavage for 5
      days before a single dose of t-BHP (ip; 0.2 mmol/kg ) significantly lowered serum
      levels of the hepatic enzyme markers lactate dehydrogenase (LDH) and alanine
      (ALT) and aspartate (AST) aminotransferase, and reduced oxidative stress of the
      liver by evaluating malondialdehyde (MDA) and glutathione (GSH).
      Histopathological evaluation of the rat livers revealed that PCA reduced the
      incidence of liver lesions, including hepatocyte swelling, leukocyte
      infiltration, and necrosis induced by t-BHP. In addition, PCA inhibited t-BHP
      induced tyrosine phosphorylation, an implication of the activation of a stress
      signal pathway, in the liver. These results indicate that PCA protects against t
      BHP-induced hepatotoxicity by its antioxidant and anti-inflammatory
      characteristics accompanied by blocking of stress signal transduction.

PMID- 11955671
TI  - Induction of cytochromes P450 1A1 and 1B1 in human lung adenocarcinoma CL5 cells
      by frying-meat emission particulate.
AB  - The effect of airborne frying-meat emission particulate (FMEP) on cytochrome P450
      (P450)-dependent monooxygenase was determined using human lung adenocarcinoma
      cell line CL5 treated with organic extract of FMEP prepared from beef, fish or
      pork. Treatment with fish FMEP extract caused greater increases of intracellular
      peroxide production and glutathione content than did beef and pork FMEP extracts.
      Treatment with 200 microg/ml beef, fish or pork FMEP extract for 6 h increased
      benzo[a]pyrene hydroxylase, 7-ethoxyresorufin and methoxyresorufin O-dealkylases
      activities in S9. Immunoblot analysis of S9 proteins from control cells and cells
      treated with FMEP extracts revealed that the airborne particulates increased
      proteins immunorelated to CYP1A1 and CYP1B1. Northern blot analysis of total
      cellular RNA from controls and cells treated with FMEP extracts showed that the
      cooking by-products increased the levels of CYP1A1 and CYP1B1 mRNA. Treatment
      with 1 microM dibenzo[a,h]anthracene for 6 h increased monooxygenase activities,
      CYP1A1 and CYP1B1 protein and mRNA levels in CL5 cells. Beef FMEP extract and
      dibenzo[a,h]anthracene also induced CYP1A1 and CYP1B1 in human lung carcinoma NCI
      H322 cells. The present finding demonstrates that airborne particulates generated
      during the frying of beef, fish and pork can induce carcinogen-metabolizing
      CYP1A1 and CYP1B1 in the human lung-derived cell line CL5.

PMID- 11955672
TI  - Toxicity of ad lib. overfeeding: effects on cardiac tissue.
AB  - The aim of the present study was to determine the effects of ad lib. overfeeding
      and of dietary restriction (DR) on oxidative stress in cardiac tissue.
      Lipoperoxide concentrations were decreased and antioxidant enzymes were increased
      in moderate-DR-fed rats. Severe-DR induced increased lipoperoxide concentrations.
      Overfeeding increased lipoperoxide levels in cardiac tissue. Total superoxide
      dismutase (SOD) and Cu-Zn superoxide dismutase (Cu-Zn SOD) activities were
      decreased in cardiac tissue at 35 days of overfeeding. As no changes in
      glutathione peroxidase (GSH-Px) were observed in overfed rats, while SOD and Cu
      Zn SOD activities were decreased in these animals, it is assumed that superoxide
      anion is an important intermediate in the toxicity of ad lib. overfeeding.
      Overfeeding induced alterations in markers of oxidative stress in cardiac tissue.

PMID- 11955673
TI  - Effect of aflatoxins on testicular steroidogenesis and amelioration by vitamin E.
AB  - The potential of aflatoxin to affect testicular steroidogenesis and its
      amelioration by vitamin E was assessed in the present investigation. Oral
      administration of aflatoxin (25 and 50 microg/animal/day) for 45 days to adult
      mice caused, as compared with control, a dose-dependent significant rise in
      cholesterol content. However, the activities of 3beta- and 17beta-hydroxysteroid
      dehydrogenases and serum testosterone levels were significantly reduced in
      aflatoxin-treated mice as compared with the controls. Pretreatment with vitamin E
      (2 mg/animal/day, orally) significantly ameliorated aflatoxin-induced changes as
      compared with aflatoxin treatment alone. The present investigation clearly
      indicates that vitamin E ameliorates aflatoxin-induced changes in
      steroidogenesis.

PMID- 11955674
TI  - Experimental and simulation studies of heat flow and heterocyclic amine
      mutagen/carcinogen formation in pan-fried meat patties.
AB  - Heterocylic amine (HA) compounds formed in the cooking of certain foods have been
      shown to be bacterial mutagens and animal carcinogens, and may be a risk factor
      for human cancer. To help explain the variation observed in HA formation under
      different cooking conditions, we have performed heat-flow simulations and
      experiments on the pan-frying of beef patties. The simulations involve modeling
      the heat flow within a meat patty using empirically derived thermal transport
      coefficients for the meat. The predicted temperature profiles are used to
      integrate the Arrhenius rate equation to estimate the concentration of HAs formed
      in the meat. We find that our simulations accurately model experimentally
      determined temperature profiles, cooking times, HA spatial distributions and
      total HA formation in patties that are flipped once during the pan-frying
      process. For patties flipped every 60 s, the simulations qualitatively agree with
      experiment in predicting reduced cooking times and HA formation relative to the
      singly-flipped patties. However, the simulations overestimate the effect of rapid
      flipping on cooking times and underestimate the effect of flipping on total HAs
      formed. These results suggest that the dramatic reductions in HA formation due to
      rapid flipping may be due to factors other than the heating process or that there
      is a critical feature of the flipping process that is not captured in our model.

PMID- 11955675
TI  - Statistically designed experiments in a tiered approach to screen mixtures of
      Fusarium mycotoxins for possible interactions.
AB  - This paper presents a test strategy to detect interactive effects between several
      mycotoxins using a DNA synthesis inhibition assay in L929 cells. The joint action
      of the Fusarium mycotoxins T-2 toxin (T2), deoxynivalenol (DON), nivalenol (NIV),
      zearalenone (ZEA) and fumonisin (FB1) was studied in a tiered approach. In the
      first stage, the mycotoxins were tested either jointly in a five-compound
      mixture, or individually. At the highest dose level, the mixture showed a clear
      less than additive action of the mycotoxins, as compared to the effects of the
      five individual compounds, whereas at lower dose levels the mycotoxins behaved
      additive. In the second stage, the non-additivity as established in the first
      experiment was further analyzed with a central composite design to detect
      interactions between specific mycotoxins in the mixture. This experiment
      confirmed less than additivity for five of the mixes tested. However, it also
      revealed four significant synergistic interactions between mycotoxins. Finally,
      two interactions that were established in stage 2 were further studied in full
      factorial designs involving two mycotoxins. One of the interactions observed in
      the central composite design was retrieved whereas the other two-factor
      interaction was not. It was concluded that several classes of mycotoxins when
      present simultaneously in a mixture might show interaction. The effect of the
      mixture cannot be predicted solely on the basis of the effect of the individual
      compounds.

PMID- 11955676
TI  - The effect of paclitaxel on 2-aminofluorene-DNA adducts formation and arylamine N
      acetyltransferase activity and gene expression in human lung tumor cells (A549).
AB  - In this study, paclitaxel was used to determine inhibition of arylamine N
      acetyltransferase (NAT) activity, gene expression and 2-aminofluorene-DNA adduct
      formation in a human lung tumor cell line (A549). The activity of NAT was
      measured by HPLC assaying for the amounts of N-acetyl-2-aminofluorene (2-AAF) and
      remaining 2-aminofluorene (2-AF). Human lung tumor cell cytosols and intact cells
      were used for examining NAT activity and carcinogen-DNA adduct formation. The
      results demonstrated that NAT activity, gene expression (NAT1 mRNA) and 2-AF-DNA
      adduct formation in human lung tumor cells were inhibited and decreased by
      paclitaxel in a dose-dependent manner. The effects of paclitaxel on the values of
      the apparent Km and Vmax of NAT from human lung tumor cells were also determined
      in both examined systems. The result also indicated that paclitaxel decreased the
      apparent values of Km and Vmax from human lung tumor cells in both cytosol and
      intact cells. Thus, paclitaxel is an uncompetitive inhibitor to NAT enzyme.

PMID- 11955677
TI  - The effect of paclitaxel on gene expression and activity of arylamine N
      acetyltransferase and DNA-2-aminofluorene adduct formation in human leukemia HL
      60 cells.
AB  - N-Acetylation is recognized as the first step in arylamine metabolism. The enzyme
      responsible for N-acetylation is called arylamine N-acetyltransferase (NAT),which
      uses acetyl coenzyme A as the acetyl group donor. Paclitaxel has been shown to
      exhibit antineoplastic and anticancer activity. In this study, paclitaxel was
      selected to determine the inhibition of arylamine N-acetyltransferase activity,
      gene expression (NAT mRNA) and DNA-2-aminofluorene adduct formation in human
      leukemia HL-60 cell line. Paclitaxel (0.01-l microM) did decrease the level of
      NAT mRNA in a dose-dependent manner. The results demonstrated that paclitaxel
      inhibited NAT activity and DNA-2-aminofluorene adduct formation in human leukemia
      HL-60 cells in a dose-dependent manner. Using standard steady-state kinetic
      analysis, it was demonstrated that paclitaxel was a possible uncompetitive
      inhibitor to NAT activity in cytosols based on the decrease in apparent values of
      K(m) and V(max). This report is the first demonstration that paclitaxel affected
      human leukemia HL-60 cells NAT activity and DNA-2-aminofluorene adduct formation.

PMID- 11955678
TI  - Dose- and time-response studies of sodium o-phenylphenate urinary bladder
      carcinogenicity in rats.
AB  - Dose- and time-response studies of urinary bladder carcinogenesis due to orally
      administered sodium o-phenylphenate (OPP-Na) were performed using 5-week-old male
      Fischer 344 rats given diets containing 0 (control), 2500, 5000, 10,000, 15,000
      or 20,000 ppm OPP-Na for 104 weeks and fed basal diets until 112 weeks
      (experiment 1). In addition, rats received diets containing 20,000 ppm OPP-Na for
      0 (control), 12, 24, 52 or 104 weeks and were killed at week 112 (experiment 2).
      In experiment 1, the transitional cell carcinoma (TCC) was the major tumor type
      in the urinary bladder, and the dose-response curve was steep with many tumors
      occurring at the high doses of 15,000 and 20,000 ppm. The virtually safe dose at
      a risk level of 10(-6) for TCCs and papillomas was estimated to be 144 ppm by the
      Weibull model, a high value similar to that for sodium saccharin. In experiment
      2, a few TCCs developed after 24 weeks of treatment, but the time-response curve
      was also steep with the majority of lesions occurring after longer exposure
      periods. Based on the observed steepness in dose- and time-responses, any implied
      cancer risk of OPP-Na at the low doses of interest to man must be considered to
      be very small.

PMID- 11955679
TI  - Developmental toxicity of flupyrazofos, a new organophosphorus insecticide, in
      rats.
AB  - Flupyrazofos is a new type of pyrazole organophosporus insecticide, which has a
      high activity against the diamond-back moth (Plutella xylostella). The potential
      of this agent to induce developmental toxicity was investigated in the Sprague
      Dawley rat. One hundred mated females (sperm in vaginal LAVAGE=day 0) were
      distributed among three treated groups and a control group. Flupyrazofos was
      administered by gavage to pregnant rats from days 7-17 of gestation at dose
      levels of 0, 5, 12 and 30 mg/kg/day. All dams were subjected to the caesarean
      section on day 20 of gestation and their fetuses were examined for external,
      visceral and skeletal abnormalities. At 30 mg/kg, maternal effects including
      mortality (4.3%), clinical signs of toxicity, decreased food intake, suppressed
      body weight, and increased weight of adrenal glands, kidney and heart were
      observed in dams. Litter values for corpora lutea, implantations, sex ratio and
      litter size were within the normal range. However, a reduction in the fetal
      weight and an increase in the incidence of fetal skeletal retardations were
      observed. At 12 mg/kg, toxic effects including mortality (4.2%), nasal discharge
      and some fetal skeletal retardation were observed. There were no signs of either
      maternal toxicity or embryotoxicity at 5 mg/kg. The results show that
      flupyrazofos induces fetal growth retardation only at maternally toxic doses in
      rats and the no-observed-adverse-effect levels (NOAELs) of this agent are
      considered to be 5 mg/kg for both dams and fetuses.

PMID- 11955681
TI  - Alternatives to animal testing: information resources via the Internet and World
      Wide Web.
AB  - Many countries, including the United States, Canada, European Union member
      states, and others, require that a comprehensive search for possible alternatives
      be completed before beginning some or all research involving animals. Completing
      comprehensive alternatives searches and keeping current with information
      associated with alternatives to animal testing is a challenge that will be made
      easier as people throughout the world gain access to the Internet and World Wide
      Web. Numerous Internet and World Wide Web resources are available to provide
      guidance and other information on in vitro and other alternatives to animal
      testing. A comprehensive Web site is Alternatives to Animal Testing on the Web
      (Altweb), which serves as an online clearinghouse for resources, information, and
      news about alternatives to animal testing. Examples of other important Web sites
      include the joint one for the (US) Interagency Coordinating Committee on the
      Validation of Alternative Methods (ICCVAM) and the National Toxicology Program
      (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods
      (NICEATM) and the Norwegian Reference Centre for Laboratory Animal Science and
      Alternatives (The NORINA database). Internet mailing lists and online access to
      bulletin boards, discussion areas, newsletters, and journals are other ways to
      access and share information to stay current with alternatives to animal testing.

PMID- 11955682
TI  - Cancer information resources: digital and online sources.
AB  - The Internet is becoming an increasingly important source of information on
      cancer. This article highlights major sites of credible information on cancer and
      describes the types of information each of these sites contains. Large
      directories that help point the visitor to additional cancer-related sites are
      described, as are searchable databases of information on cancer as a disease, its
      diagnosis, and treatment. Sources of information on chemical carcinogens,
      mechanistic studies, and applied cancer toxicology are also described. These
      Internet sources of cancer information address the needs of toxicologists,
      environmental and occupational health scientists, cancer researchers and
      clinicians, government regulators, the public, and cancer survivors and their
      caregivers.

PMID- 11955683
TI  - Developmental toxicity: web resources for evaluating risk in humans.
AB  - This review presents a brief overview of Internet resources that provides
      information on developmental toxicity. The advantages and limitations of these
      resources for evaluating human risk and where each one is useful for informing
      various stages of the risk assessment process (i.e. hazard characterization, dose
      response assessment, exposure assessment and risk characterization) are reviewed.
      How these Internet resources can be utilized to obtain information on and
      evaluate the developmental risk associated with exposures during pregnancy will
      be illustrated using toluene. Translating information derived from laboratory and
      human population studies into clinical management prescriptions for individual
      patients is difficult. With the increasing availability of Internet resources
      that provide information relevant for developmental risk assessments, health care
      professionals will be better equipped to make more accurate estimations of
      potential risk for their patients.

PMID- 11955684
TI  - Web resources for drug toxicity.
AB  - Information on drug toxicity is used primarily by three segments of the health
      care industry: the consumer or patient, healthcare practitioners, and research
      and development (R&D) scientists in the pharmaceutical industry. The major focus
      of both consumers and health care practitioners is the provision of suitable
      information for the safe use of drugs for both individuals and specific patient
      populations. Therefore, accurate information on potential side effects and drug
      drug and food-drug interactions is critical. For pharmaceutical scientists, the
      use of toxicity information is more complex and has become an essential part of
      the R&D process. The high rate of failures in drug development has precipitated
      the utilization of all available resources to gather relevant information that
      may improve the process of drug development. The web is a growing source of
      information and services for the pharmaceutical industry. Web-based resources for
      non-clinical drug development include tools for virtual discovery such as silico
      ADME/Toxicity programs, access to information regarding in vitro and in vivo
      testing, new data management options, and the latest regulatory guidelines and
      industry news. These resources are reviewed from the perspective of a
      toxicologist.

PMID- 11955685
TI  - Mining environmental toxicology information: web resources.
AB  - Environmental toxicology is the study of the ecological effects of anthropogenic
      substances released into the environment. It is a relatively diverse field
      addressing impacts to aquatic and terrestrial organisms and communities. The
      determination of potential risk associated with toxic agents is of interest to
      government regulators, industry, researchers, private organizations and citizen
      groups. In assessing the ecological risk associated with a chemical stressor, it
      is important to establish linkages between likely exposure concentrations and
      adverse effects to ecological receptors. To do so requires access to reliable
      information resources. The proper application of such data requires familiarity
      with the scientific literature and keeping abreast of new and emerging issues as
      well as state-of-the-art research findings and methods. In addition, an
      understanding of government regulations as they relate to environmental issues is
      also of primary interest. The advent of the Web has made these tools accessible
      at computer desktops. This review focuses on currently available free Web
      resources related to environmental toxicology, specifically those which address
      available empirical data sources, predictive tools and publications of interest
      such as standard test methods, guidance documents and governmental regulations.

PMID- 11955686
TI  - Electronic information resources for food toxicology.
AB  - This manuscript provides a brief overview of many useful Internet resources
      concerning food toxicology. Specific topic areas include pesticide residues, food
      additives, natural toxins, environmental contaminants, and food allergies;
      numerous links and evaluative information are provided within each topic area.
      Several helpful Internet resources have been identified and include government,
      industry, academic, and consumer sites.

PMID- 11955687
TI  - Forensic toxicology: web resources.
AB  - Forensic toxicology is the study and practice of the application of toxicology to
      the purposes of the law. The internet provides abundant web-sites and resources
      for the practicing forensic toxicologist and those interested in the field of
      forensic toxicology. This review includes a description of web-sites, databases
      of toxicological and analytical data, and web-based journals, forums and mailing
      lists.

PMID- 11955688
TI  - Genetic toxicology: web resources.
AB  - Genetic toxicology is the scientific discipline dealing with the effects of
      chemical, physical and biological agents on the heredity of living organisms. The
      Internet offers a wide range of online digital resources for the field of Genetic
      Toxicology. The history of genetic toxicology and electronic data collections are
      reviewed. Web-based resources at US National Library of Medicine (NLM), including
      MEDLINE, PUBMED, Gateway, Entrez, and TOXNET, are discussed. Search strategies
      and Medical Subject Headings (MeSH) are reviewed in the context of genetic
      toxicology. The TOXNET group of databases are discussed with emphasis on those
      databases with genetic toxicology content including GENE-TOX, TOXLINE, Hazardous
      Substances Data Bank, Integrated Risk Information System, and Chemical
      Carcinogenesis Research Information System. Location of chemical information
      including chemical structure and linkage to health and regulatory information
      using CHEMIDPLUS at NLM and other databases is reviewed. Various government
      agencies have active genetic toxicology research programs or use genetic
      toxicology data to assist fulfilling the agency's mission. Online resources at
      the US Food and Drug Administration (FDA), the US Environmental Protection Agency
      (EPA), the National Institutes of Environmental Health Sciences, and the National
      Toxicology Program (NTP) are outlined. Much of the genetic toxicology for
      pharmaceuticals, industrial chemicals and pesticides that is performed in the
      world is regulatory-driven. Regulatory web resources are presented for the laws
      mandating testing, guidelines on study design, Good Laboratory Practice (GLP)
      regulations, and requirements for electronic data collection and reporting. The
      Internet provides a range of other supporting resources to the field of genetic
      toxicology. The web links for key professional societies and journals in genetic
      toxicology are listed. Distance education, educational media resources, and job
      placement services are also available online in the field of genetic toxicology.
      As molecular biology and computational tools improve, new areas within genetic
      toxicology such as structural activity relationship analysis, mutational spectra
      databases and toxicogenomics, now have resources online as well.

PMID- 11955689
TI  - Human health risk assessment: selected Internet and world wide web resources.
AB  - The world wide web (WWW) has become a valuable source of 24 hour-a-day access to
      information needed by human health risk assessors. Various web sites and other
      Internet resources provide information needed for human hazard identification,
      dose-response evaluation, exposure assessment, risk characterization, and risk
      management. Information on risk communication is also available. Substantial
      collections of information on multiple aspects of risk assessment are found in
      sites sponsored by RiskWorld, the (US) EPA's National Center for Environmental
      Assessment (NCEA), the (US) National Library of Medicine's TOXNET, the (US)
      Agency for Toxic Substances and Disease Registry (ATSDR), and the International
      Programme on Chemical Safety (IPCS). Also valuable are various web sites
      providing information on the physical and chemical properties of chemicals, the
      environmental fate and transport of chemicals, government regulations, and
      guidance and training for performing risk assessments. Several professional
      societies and other organizations have web sites addressing risk assessment
      issues and information, and there are Internet mailing lists for online help and
      for sharing information and perspectives. We classify selected web sites
      according to user needs and provide the reader with a collection of selected
      sites that can serve as entry points to risk assessment-related web resources.

PMID- 11955690
TI  - Internet resources for occupational and environmental health professionals.
AB  - The Internet = s global reach offers new powerful tools to professionals in
      Occupational and Environmental Health (OEH). The World Wide Web includes
      extensive free and commercially available reference materials on toxicology,
      regulatory issues, environmental epidemiology and prevention programs. Much of
      this especially useful content is inaccessible to general Web-based search
      engines. Effective use of the Web requires discovery and familiarity with sites
      housing query engines for technical databases. Although the Web = s structure and
      capacity is so dynamic that any listing is incomplete, introductions to many
      resources are provided in this article. The Internet also offers professionals
      electronic access to one another, for collegial discourse. Electronic mailing
      lists provide assembly points for collaboration and guidance about technical
      issues. Several specialty forums for OEH professionals are also discussed.

PMID- 11955692
TI  - Radiation information and resources on-line.

PMID- 11955691
TI  - WEB resources for pesticide toxicology, environmental chemistry, and policy: a
      utilitarian perspective.
AB  - Information about pesticides has grown exponentially over the last four decades
      and is marked by a diversity of sources including government, universities,
      environmental advocates, and industry. The internet has made access to this
      unprecedented amount of information faster than ever, but judging the validity
      and usefulness of the information is problematic. To avoid turning this
      discussion of web resources for pesticide information into a narrative about a
      personal 'top ten' list, a utilitarian perspective of resources useful to a
      research, educator, and risk communicator is elucidated. Useful web sites are fit
      into the context of information needed for risk assessment, which includes hazard
      identification, dose-response relationships, exposure assessment, and risk
      characterization. In addition resources for pesticide policy and regulations are
      considered. Specific ways in which the sites are useful are discussed along with
      information about site updating and validation of information.

PMID- 11955693
TI  - Internet resources for veterinary toxicologists.
AB  - The informational needs of veterinary toxicologists are diverse due to their
      involvement in clinical, research and regulatory toxicology. The internet
      provides an important tool for assessing a wide array of useful toxicologic
      information that is otherwise not readily available. Internet resources utilized
      by veterinary toxicologists include governmental, commercial, academic and non
      profit websites.

PMID- 11955708
TI  - Coordinate regulation and synergistic actions of BMP4, SHH and FGF8 in the
      rostral prosencephalon regulate morphogenesis of the telencephalic and optic
      vesicles.
AB  - We investigated the roles of bare morphogenetic protein (BMP), sonic hedgehog
      (SHH) and fibroblast growth factor (FGF)-expressing signaling centers in
      regulating the patterned outgrowth of the telencephalic and optic vesicles.
      Implantation of BMP4 beads in the anterior neuropore of stage 10 chicken embryos
      repressed FGF8 and SHH expression. Similarly, loss of SHH expression in Shh
      mutant mice leads to increased BMP signaling and loss of Fgf8 expression in the
      prosencephalon. Increased BMP signaling and loss of FGF and SHH expression was
      correlated with decreased proliferation, increased cell death, and hypoplasia of
      the telencephalic and optic vesicles. However, decreased BMP signaling, through
      ectopic expression of Noggin, a BMP-binding protein, also caused decreased
      proliferation and hypoplasia of the telencephalic and optic vesicles, but with
      maintenance of Fgf8 and Shh expression, and no detectable increase in cell death.
      These results suggest that optimal growth requires a balance of BMP, FGF8 and SHH
      signaling. We suggest that the juxtaposition of Fgf8, Bmp4 and Shh expression
      domains generate patterning centers that coordinate the growth of the
      telencephalic and optic vesicles, similar to how Fgf8, Bmp4 and Shh regulate
      growth of the limb bud. Furthermore, these patterning centers regulate regional
      specification within the forebrain and eye, as exemplified by the regulation of
      Emx2 expression by different levels of BMP signaling. In summary, we present
      evidence that there is cross-regulation between BMP-, FGF- and SHH-expressing
      signaling centers in the prosencephalon which regulate morphogenesis of, and
      regional specification within, the telencephalic and optic vesicles.

PMID- 11955709
TI  - Immunohistochemical localization and quantification of glucose transporters in
      the mouse brain.
AB  - A family of seven facilitative glucose transporters (Glut1-5, 7 and 8) mediates
      the cellular uptake of glucose. In the brain, Glut2, Glut5 and Glut8 are found at
      relatively low levels whereas Glut1, Glut3 and Glut4 were reported in abundance
      in several brain regions. Using immunofluorescence, this study investigated,
      compared and quantified the localization of the brain major glucose transporters,
      Glut1, Glut3 and Glut4, in the different cerebral areas of CD1 mice. Most of the
      staining of Glut1, Glut3 and Glut4 in the mouse brain coincides with observations
      made in rats. The results confirm the cortical neuropil distribution of Glut3,
      the prominence of this transporter in the mossy fiber field of the hippocampus
      and the Glut3 and Glut4 immunostaining of the hippocampal pyramidal cell layer.
      The present study also reports novel localizations of the transporters such as
      the presence of Glut3 in neuronal perikarya, Glut4-labeled neurons in the CA3 of
      the hippocampus and the subiculum. In the cerebellum, Glut3 shows subcellular
      localization to the base of the Purkinje cell bodies near the axon hillock.
      Furthermore, an important population of Golgi cells was found to be strongly
      immunostained for Glut4 in the granular cell layer of the cerebellum. The
      quantification results suggest that the relative abundance of Glut1 in the
      frontal and motor cortices coincides well with the high-energy demands of these
      brain regions. However, the Glut4-selective abundance in cerebral motor areas
      supports its suggested role in providing the energy needed for the control of the
      motor activity. The reported neuropil distribution of Glut3 seems to uphold its
      suggested role in synaptic energy provision and neurotransmitter synthesis. We
      conclude that the cellular and regional distributions of the glucose transporters
      in the rodent brain seem to be relevant to their corresponding functions.

PMID- 11955710
TI  - Gene expression patterns during enhanced periods of visual cortex plasticity.
AB  - During a critical period in its postnatal development the mammalian visual cortex
      displays susceptibility to experience-dependent alterations of neuronal response
      properties. Plasticity represents an integrated set of developmental processes
      controlled by a transcriptional hierarchy that coordinates the action of many
      genes. To illuminate the expression of these critical genes, we examined gene
      expression patterns of 18371 non-redundant cDNAs in the visual cortex of cats at
      birth, at eye opening, at the peak of the critical period of eye dominance
      plasticity and in the adult cat using filter-based cDNA arrays and software-based
      hierarchical cluster analysis. We identified a small set of genes that were
      selectively expressed during the peak of the critical period for plasticity. We
      further examined the patterns of expression of these genes by analyzing the gene
      expression pattern of dark-reared chronologically older animals that are known to
      retain this ocular dominance plasticity beyond the chronologically defined
      critical period. This additional cluster assessment allowed us to separate age
      related changes in the patterns of gene expression from plasticity-related
      changes, thus identifying a subset of genes that we define as plasticity
      candidate genes. Those plasticity candidate genes that have previously
      characterized functions include participants in second messenger systems, in cell
      adhesion, in transmitter recycling and cytokines, among others. Comparison of
      cDNA array quantitation with reverse transcription-polymerase chain reaction
      showed almost identical expression profiles for three genes that we examined. The
      expression pattern of one identified gene, opioid binding cell adhesion molecule,
      from the cDNA array analysis, is also in agreement with immunocytochemical
      results. We conclude that the approach of high-density cDNA array hybridization
      can be used as a useful tool for examining a complex phenomenon of developmental
      plasticity since it is amenable to multiple developmental stage gene expression
      comparisons.

PMID- 11955711
TI  - Coexistence of translocated cytochrome c and nitrated protein in neurons of the
      rat cerebral cortex after oxygen and glucose deprivation.
AB  - Changes in the distribution of immunoreactive cytochrome c and protein nitration
      were studied in the rat cerebral cortex after oxygen and glucose deprivation by
      bright field, confocal and electron microscopy. In control cerebral cortex,
      nitrotyrosine immunoreactivity indicating protein nitration was found mostly in
      the neuronal nuclear region, with only a small amount distributed in the cytosol,
      whereas cytochrome c immunoreactivity was found at the inner membrane and in the
      intermembrane space of the mitochondria. During the recovery phase after oxygen
      and glucose deprivation, cytochrome c immunoreactivity was released from the
      intermembrane space of swollen mitochondria into the surrounding cytosol. The
      cytosol now also displayed nitrotyrosine immunoreactivity, which had diminished
      in the nuclear region. Both immunoreactivities were dispersed throughout the soma
      and processes of the cortical neurons. These changes were largely prevented by
      the administration of cyclosporin A, which inhibits both the mitochondrial
      permeability transition and the neuronal isoform of nitric oxide synthase while
      blocking the induction of the inducible isoform. Ischemia/reperfusion injury
      increases the production of nitric oxide, reactive oxygen species and
      intracellular factors that damage the mitochondria and liberate apoptotic
      factors. We suggest that translocation of cytochrome c from the mitochondria to
      the cytosol, which has been shown to precede the mitochondrial permeability
      transition, could result from peroxynitrite-mediated nitration. This phenomenon
      is attenuated by cyclosporin A administration, suggesting a neuroprotective role
      for this agent.

PMID- 11955712
TI  - Altered expression of voltage-dependent calcium channel alpha(1) subunits in
      temporal lobe epilepsy with Ammon's horn sclerosis.
AB  - Voltage-dependent calcium channels, the initial components in the calcium
      signalling cascade, are increasingly being recognised as relevant factors in the
      pathology of epilepsy. To further characterise their role in temporal lobe
      epilepsy associated with Ammon's horn sclerosis, we investigated the
      immunohistochemical distribution of five different voltage-dependent calcium
      channel alpha(1) subunits (alpha(1A), alpha(1B), alpha(1C), alpha(1D), alpha(1E))
      in 14 hippocampal specimens of patients with Ammon's horn sclerosis in comparison
      with eight autopsy control cases. In epilepsy specimens an increased
      immunoreactivity was observed for alpha(1A), alpha(1B), alpha(1D) and alpha(1E)
      in the neuropil of the dentate gyrus molecular layer. Dentate gyrus granule cells
      and residual CA3 pyramidal neurones showed enhanced immunoreactivity for
      alpha(1A), while labelling of these neurones was decreased for alpha(1C).
      Astrocytes in Ammon's horn sclerosis specimens were strongly immunoreactive for
      the alpha(1C) subunit contrasting with an absent astrocytic alpha(1C) labelling
      in controls. Our results suggest that the expression of calcium channels in
      neurones and glial cells is dynamically regulated in temporal lobe epilepsy,
      supporting the relevance of calcium signalling pathways for this disease.

PMID- 11955714
TI  - Presence of Ras guanyl nucleotide-releasing protein in striosomes of the mature
      and developing rat.
AB  - Ras signal transduction pathways have been implicated as key regulators in
      neuroplasticity and synaptic transmission in the brain. These pathways can be
      modulated by Ras guanyl nucleotide exchange factors, (GEF) which activate Ras
      proteins by catalysing the exchange of GDP for GTP. Ras guanyl nucleotide
      releasing protein (RasGRP), a recently discovered Ras GEF, that links
      diacylglycerol and probably calcium to Ras signaling pathways, is expressed in
      brain as well as in T-cells. Here, we have used a highly selective monoclonal
      antibody against RasGRP to localize this protein within the striatum and related
      forebrain structures of developing and adult rats. RasGRP immunolabeling was
      found to be widespread in the mature and developing rat forebrain. Most notably,
      it presented a prominent patchy distribution throughout the striatum at birth and
      at all postnatal ages examined. These patches were found to correspond with the
      striosomal compartment of the striatum, as identified by micro-opioid receptor
      labeling in the adult. RasGRP-immunoreactivity was also observed in the matrix
      like compartment surrounding these patches/striosomes but appeared later in
      development and was always weaker than in the patches. In both striatal
      compartments, RasGRP was exclusively expressed by medium-sized spiny neurons and
      showed no preference for neurons that project either directly or indirectly to
      the substantia nigra. At the ultrastructural level, immunogold labeling of RasGRP
      was confined to the cell bodies and dendritic shafts of these output neurons. We
      conclude that the prominent expression of RasGRP in striosomes may be of
      significance for diacylglycerol signaling in the striatum, and could be of
      importance for the processing of limbic-related activity within the basal
      ganglia.

PMID- 11955713
TI  - Spontaneous recurrent seizures after pilocarpine-induced status epilepticus
      activate calbindin-immunoreactive hilar cells of the rat dentate gyrus.
AB  - Although it is now established that neurogenesis of dentate gyrus granule cells
      increases after experimental seizures, little is currently known about the
      function of the new granule cells. One question is whether they become integrated
      into the network around them. Recent experiments that focused on the newly born
      granule cells in the hilus showed that indeed the new cells appear to become
      synchronized with host hippocampal neurons [Scharfman et al. (2000) J. Neurosci.
      20, 6144-6158]. To address this issue further, we asked whether the new hilar
      granule cells were active during spontaneous limbic seizures that follow status
      epilepticus induced by pilocarpine injection. Thus, we perfused rats after
      spontaneous seizures and stained sections using antibodies to c-fos, a marker of
      neural activity, and calbindin, a marker of the newly born hilar granule cells
      [Scharfman et al. (2000) J. Neurosci. 20, 6144-6158]. We asked whether calbindin
      immunoreactive hilar neurons were also c-fos-immunoreactive.C-fos was highly
      expressed in calbindin-immunoreactive hilar neurons. Approximately 23% of hilar
      cells that expressed c-fos were double-labeled for calbindin. In addition, other
      types of hilar neurons, i.e. those expressing parvalbumin or neuropeptide Y, also
      expressed c-fos. Yet other hippocampal neurons, including granule cells and
      pyramidal cells, had weak expression of c-fos at the latency after the seizure
      that hilar neuron expression occurred. In controls, there was very little c-fos
      or calbindin expression in the hilus.These results indicate that calbindin
      immunoreactive hilar cells are activated by spontaneous seizures. Based on the
      evidence that many of these cells are likely to be newly born, the data indicate
      that new cells can become functionally integrated into limbic circuits involved
      in recurrent seizure generation. Furthermore, they appear to do so in a manner
      similar to many neighboring hilar neurons, apparently assimilating into the local
      environment. Finally, the results show that a number of hilar cell types are
      activated during chronic recurrent seizures in the pilocarpine model, a
      surprising result given that many hilar neurons are thought to be damaged soon
      after pilocarpine-induced status epilepticus.

PMID- 11955715
TI  - A differential involvement of the shell and core subterritories of the nucleus
      accumbens of rats in attentional processes.
AB  - The nucleus accumbens comprises of two anatomically distinct subterritories: an
      inner core and an outer shell region. The distinct pattern of the core and shell
      input and output targets suggests that these two regions may mediate different
      behavioral processes. Using N-methyl-D-aspartate excitotoxic lesions in either
      the core or shell region, we investigated whether we can dissociate functionally
      these two subterritories. N-Methyl-D-aspartate-lesioned, sham-lesioned and non
      operated animals were tested for locomotor activity in an open field and in two
      behavioral paradigms known to evaluate attentional deficits, namely the pre-pulse
      inhibition of the acoustic startle reflex and latent inhibition, measured in a
      two-way active avoidance paradigm. The shell-lesioned animals showed a small but
      significant hyperactivity in the open field when compared to the core-lesioned
      and to control animals. In the pre-pulse inhibition paradigm, core-lesioned
      animals demonstrated reduced pre-pulse inhibition to the two high pre-pulse
      intensities (80 dB[A], 84 dB[A]). In the active avoidance paradigm, whereas no
      lesion effects were detected in the non-pre-exposed groups, clear attenuation of
      latent inhibition was found in the shell-lesioned rats, in comparison to both
      core-lesioned and control rats, due to improved avoidance performance of the
      shell-pre-exposed group. From these results we suggest that the two
      subterritories of the nucleus accumbens are differentially involved in attention
      related processes: the core lesion leads to significant disruption of pre-pulse
      inhibition while the shell lesion leads to heightened activity and significant
      attenuation of latent inhibition.

PMID- 11955716
TI  - Further characterization of preproenkephalin mRNA-containing cells in the rodent
      globus pallidus.
AB  - The globus pallidus (external pallidum of primates) is an essential nucleus
      within basal ganglia circuitry, in part because it receives at least one-half of
      striatal efferent projections. Neurons of the globus pallidus can be divided into
      subpopulations based on anatomical, physiological, and chemical features. Globus
      pallidus neurons project to several structures (the striatum, subthalamic
      nucleus, entopeduncular nucleus, and substantia nigra pars reticulata), have one
      of two alternative waveforms (positive/negative versus negative/positive),
      contain either the calcium binding protein parvalbumin or the neuropeptide
      precursor preproenkephalin mRNA and show differential immediate early gene
      responses to dopamine receptor agonists and antagonists. The objective of the
      present study was to characterize in greater detail the preproenkephalin mRNA
      containing pallidal neurons using Sprague-Dawley rats. In situ hybridization for
      preproenkephalin mRNA was combined with immunocytochemical detection of: (i) the
      neuron-specific nuclear protein, NeuN, (ii) FluoroGold-labeled pallidostriatal
      and pallidosubthalamic cells, or (iii) Fos induced by either systemic combined D1
      class/D2-class dopamine receptor agonists or a D2-class receptor antagonist.
      These experiments demonstrated that a substantial population (42%) of globus
      pallidus neurons contains preproenkephalin mRNA, and that globus pallidus neurons
      retrogradely labeled after FluoroGold injections into the striatum are more
      frequently preproenkephalinergic, compared to the population of
      pallidosubthalamic neurons. Furthermore, systemic administration of a D2 receptor
      antagonist, eticlopride, induced Fos immunoreactivity predominantly in globus
      pallidus neurons expressing preproenkephalin mRNA, while combined administration
      of D1 and D2 receptor agonists induced Fos predominantly in pallidal neurons
      lacking preproenkephalin mRNA.These results support the conclusion that
      preproenkephalin mRNA identifies one of the two major subpopulations of pallidal
      neurons. This preproenkephalin mRNA-expressing pallidal subpopulation
      preferentially targets the striatum and is more readily activated in its
      immediate early gene expression by D2 receptor antagonists than by dopamine
      receptor agonists. This projection provides a pallidal substrate for the
      dopaminergic regulation of striatal information processing.

PMID- 11955717
TI  - Up-regulation of the G(q/11alpha) protein and protein kinase C during the
      development of sensitization to morphine-induced hyperlocomotion.
AB  - It has been recognized that protein kinase C (PKC) pathway is involved in the
      synaptic plasticity. The present study was then designed to examine the changes
      in G(q/11alpha) and G(betagamma) subunits and PKC activity on sensitization to
      the morphine-induced hyperlocomotion. Repeated subcutaneous administration of
      morphine every 72 h produced sensitization to the morphine-induced
      hyperlocomotion. In morphine-sensitized mice, the protein level of G(q/11alpha)
      subunit in the limbic forebrain including the nucleus accumbens, but not in the
      lower midbrain containing the ventral tegmental area, was markedly increased,
      whereas the levels of G(betagamma) subunit were not altered in either areas.
      Under these conditions, the levels of membrane-bound phosphorylated-PKC in the
      limbic forebrain was clearly up-regulated by intermittent morphine treatment. We
      also found the lack of changes in the level of the regulator of G protein
      signaling 4, which is a specific G(q/11alpha)-dependent GTPase activating
      protein, in the limbic forebrain obtained from morphine-sensitized mice. These
      results indicate that the up-regulation of membrane-bound PKC following
      intermittent morphine treatment results from the increase in levels of
      G(q/11alpha) protein. In order to investigate the direct involvement of PKC in
      the morphine-induced hyperlocomotion, the locomotion induced by acute morphine
      treatment in the presence or absence of a PKC inhibitor was measured. A specific
      PKC inhibitor Ro-32-0432 given intracerebroventricularly caused a dose-dependent
      inhibition of morphine-induced hyperlocomotion. These findings suggest that the
      up-regulation of G(q/11alpha)-dependent PKC activity in membranes of the limbic
      forebrain is implicated in the development of sensitization to morphine-induced
      hyperlocomotion in mice.

PMID- 11955718
TI  - Projections from the amygdaloid complex to the magnocellular cholinergic basal
      forebrain in rat.
AB  - The amygdaloid complex has a key role in the modulation of behavioral responses
      in life-threatening situations, including the direction of attentional responses
      to sensory stimuli. The pathways from the amygdala to the basal forebrain
      cholinergic system, which projects to the cortex, are proposed to contribute to
      the modulation. To further explore the topography and postsynaptic targets of
      these pathways, we investigated the projections from the different divisions of
      the lateral, basal, accessory basal, and central nuclei of the amygdala to the
      cholinergic basal forebrain in rat using a sensitive anterograde tracer,
      Phaseolus vulgaris leucoagglutinin. The most substantial projections from the
      amygdala to the basal forebrain are directed to the ventrolateral and dorsomedial
      aspects of the substantia innominata and the fundus of the striatum. The heaviest
      projections originate in the capsular, lateral, and intermediate divisions of the
      central nucleus as well as in the magnocellular and parvicellular divisions of
      the basal nucleus. Light microscopic analysis of double-stained preparations
      revealed that the distribution of amygdaloid efferents and cholinergic neurons
      overlaps most prominently in the ventrolateral substantia innominata. Despite the
      fact that the central nucleus efferents and cholinergic elements overlap in the
      ventrolateral substantia innominata, electron microscopic analysis revealed,
      first, that the postsynaptic targets of the central nucleus efferents are non
      cholinergic, probably GABAergic, neurons. Second, 80% of the synaptic contacts
      were symmetric. The present data extend previous observations showing that the
      different amygdaloid nuclei provide projections to the selective basal forebrain
      areas. Further, the central nucleus efferents modulate cholinergic neurons in the
      basal forebrain indirectly via the GABAergic interneurons.

PMID- 11955719
TI  - Expression of high levels of tubulin and microtubule-associated protein 2d in the
      neurohypophysial astrocytes of adult rat.
AB  - The hypothalamo-neurohypophysial system, containing arginine vasopressin and
      oxytocin, is well known to show reversible morphological reorganization for both
      neurons and glial cells during chronic physiological stimulation. To determine
      the molecular background for these morphological changes, we investigated the
      expression of tubulin and microtubule-associated protein (MAP) 2d in the
      neurohypophysial astrocytes, pituicytes of adult rats by using reverse
      transcription-polymerase chain reaction, western blot, and immunohistochemistry.
      The mRNA of MAP2d was expressed at higher levels than that of MAP2c in the
      neurohypophysis, cerebral cortex, and cerebellum. In contrast, predominant
      expression of mRNA of MAP2c was detected in the olfactory bulb. Western blot
      analysis showed the presence of MAP2d in the neurohypophysis, however the amount
      was below the detection level in the cerebral cortex and cerebellum. A double
      labeling study using a confocal laser scanning microscope showed intense tubulin
      immunoreactivity in the glial fibrillary acidic protein (GFAP)-positive
      pituicytes of the intact neurohypophysis. Almost no tubulin immunoreactivity was
      observed in the astrocytes of the intact cerebral cortex, cerebellum, and
      supraoptic nucleus, in contrast to strong tubulin immunoreactivity in neuronal
      dendrites and somata. Interestingly, intense tubulin immunoreactivity was also
      observed in the GFAP-positive reactive astrocytes in the immediate vicinity of
      the artificial lesion of the cerebral cortex. Electron microscopic observation
      further demonstrated the presence of a lot of microtubules in the pituicytes of
      intact rats.The present results demonstrate that pituicytes in the adult rat
      neurohypophysis expresses high levels of tubulin and MAP2d compared with normal
      brain astrocytes, and suggest that the ability of astrocytic morphological
      alteration may be at least partly ascribed to this high expression of microtubule
      proteins.

PMID- 11955720
TI  - Localization of 5-HT(2A) receptors on dopamine cells in subnuclei of the midbrain
      A10 cell group.
AB  - Considerable evidence suggests that a dysfunction of the dopamine and serotonin
      (5-hydroxytryptamine or 5-HT) neurotransmitter systems contributes to a diverse
      range of pathological conditions including schizophrenia, depression and drug
      abuse. Recent electrophysiological and behavioral studies suggest that 5-HT
      modulates dopaminergic neurons in the ventral tegmental area via activation of 5
      HT(2A) receptors. It is currently unknown if 5-HT(2A) receptors mediate their
      actions on dopaminergic neurons in the ventral tegmental area via direct or
      indirect mechanisms. This study investigated whether 5-HT(2A) receptors were
      localized on dopamine cells within the A10 dopamine subnuclei of the rat,
      including the ventral tegmental area. We discovered that 5-HT(2A) receptor-like
      immunoreactivity colocalized with tyrosine hydroxylase, a marker for dopamine
      neurons, throughout the A10 dopamine cell population. Colocalization was most
      prominent in rostral and mid A10 regions, including the paranigral, parabrachial,
      and interfascicular subnuclei. Though more rare, non-dopaminergic neurons also
      expressed 5-HT(2A) receptor immunoreactivity in the ventral tegmental area.
      Additionally, although a dense population of 5-HT(2A) immunoreactive cells was
      observed in the rostral dorsal raphe nucleus, rarely were these cells
      immunoreactive for tyrosine hydroxylase. The linear raphe A10 dopamine
      subdivisions also displayed a low degree of 5-HT(2A) receptor and tyrosine
      hydroxylase colocalization. These findings provide an anatomical basis for the
      physiological modulation of dopamine neurons in the rostral ventral tegmental
      area either directly, by 5-HT(2A) receptors localized on dopamine cells, or
      indirectly, through a non-dopaminergic mechanism. Interestingly, 5-HT(2A)
      receptors were expressed on dopamine neurons in several A10 subnuclei that
      project to mesolimbic forebrain regions implicated in drug addiction, and recent
      evidence indicates that ventral tegmental area 5-HT(2A) receptor activation may
      modulate reward-related behavior in rodents. 5-HT(2A) receptors were also
      expressed on dopamine cells in A10 subnuclei that project to forebrain areas that
      have been implicated in schizophrenia, and atypical antipsychotic drugs have high
      affinities for 5-HT(2A) receptors. Thus, findings in this study could have
      important implications for understanding 5-HT and dopamine circuitry dysfunction
      in schizophrenia.

PMID- 11955721
TI  - Presynaptic action of neurotensin on cultured ventral tegmental area dopaminergic
      neurones.
AB  - Dopamine-containing neurones of the ventral tegmental area express neurotensin
      receptors which are involved in regulating cell firing and dopamine release.
      Although indirect evidence suggests that some neurotensin receptors may be
      localised on the nerve terminals of dopaminergic neurones in the striatum and
      thus locally regulate dopamine release, a clear demonstration of such a mechanism
      is lacking and a number of indirect sites of action are possible. We have taken
      advantage of a simplified preparation in which cultured rat ventral tegmental
      area dopaminergic neurones establish nerve terminals that co-release glutamate to
      determine whether neurotensin can act at presynaptic sites. We recorded glutamate
      mediated synaptic currents that were generated by dopaminergic nerve terminals as
      an index of presynaptic function. The neurotensin receptor agonist NT(8-13)
      caused an inward current and an enhancement of the firing rate of dopaminergic
      neurones together with an increase in the frequency of spontaneous glutamate
      receptor-mediated excitatory postsynaptic currents (EPSCs). Incompatible with a
      direct excitatory action on nerve terminals, NT(8-13) failed to change the
      amplitude of individual action potential-evoked EPSCs or the frequency of
      miniature EPSCs recorded in the presence of tetrodotoxin. However, NT(8-13)
      reduced the ability of terminal D2 dopamine receptors to inhibit action potential
      evoked EPSCs in isolated dopaminergic neurones. Taken together, our results
      suggest that in addition to its well-known somatodendritic excitatory effect
      leading to an increase in firing rate, neurotensin also acts on nerve terminals.
      The main effect of neurotensin on nerve terminals is not to produce a direct
      excitation, but rather to decrease the effectiveness of D2 receptor-mediated
      presynaptic inhibition.

PMID- 11955722
TI  - GluR2-R4 AMPA subunit study in rat vestibular nuclei after unilateral
      labyrinthectomy: an in situ and immunohistochemical study.
AB  - In the present investigation, we address the question of whether the expression
      of GluR2-R4 subunits mRNAs and GluR2 and GluR4 subunits protein of the alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate
      receptors are modulated in the vestibular nuclei following unilateral
      labyrinthectomy. Specific GluR2-R4 radioactive oligonucleotides were used to
      probe sections of rat vestibular nuclei according to in situ hybridization
      methods. The signal was detected by means of film or emulsion photography. GluR2
      and GluR4 subunit expression were also measured in control and operated rats by
      use of specific monoclonal GluR2 and GluR4 antibodies. Animals were killed at
      different stages following the lesion: 1, 3 or 8 days for the in situ
      hybridization study and 4 and 8 days for the immunohistochemical study. In normal
      animals, several brainstem regions including the lateral, medial, superior and
      inferior vestibular nuclei expressed all the GluR2, GluR3 and GluR4 subunit
      mRNAs. Moreover, numerous vestibular nuclei neurons are endowed with AMPA
      receptors containing the GluR2 and the GluR4 subunits. In unilaterally
      labyrinthectomized rats, no asymmetry could be detected on autoradiographs
      between the two medial vestibular nuclei probed with the GluR2 and the GluR4
      oligonucleotide probes regardless of the delay following the lesion. However,
      compared to control, a bilateral decrease (-22%) in GluR3 gene expression was
      observed in the medial vestibular nuclei 3 days after the lesion followed by a
      return to normal at day 8 post-lesion. No significant asymmetrical changes in the
      density of GluR2- and GluR4-immunopositive cells could be detected between the
      intact and deafferented sides in any part of the vestibular nuclear complex and
      at any times (day 4 or day 8) following the lesion. Our data show that the
      removal of glutamatergic vestibular input induced an absence of modulation of
      GluR2 and GluR4 gene and subunits expression. This demonstrates that GluR2 and
      GluR4 expression do not play a role in the recovery of the resting discharge of
      the deafferented medial vestibular nuclei neurons and consequently in the
      functional restoration of the static postural and oculomotor deficits. The
      functional role of the slight and bilateral GluR3 mRNA decrease in the vestibular
      nuclei remains to be elucidated.

PMID- 11955723
TI  - Effect of pertussis toxin and N-ethylmaleimide on voltage-dependent and 
      independent calcium current modulation in serotonergic neurons.
AB  - Introduction of GTP-gamma-S into a neuronal cell spontaneously results in G
      protein activation. A possible contribution to this mechanism is that some
      receptors have a constitutive activity that stimulates GDP/GTP exchange resulting
      in increased GTPase activity of G-protein alpha subunits, leading to a
      facilitation of GTP-gamma-S binding. It follows that partial or complete
      uncoupling of receptors and G-proteins could inhibit Ca(2+) current modulation by
      GTP-gamma-S. This possibility was tested in acutely isolated rat dorsal raphe
      neurons by uncoupling the receptor and G-protein using N-ethylmaleimide and
      pertussis toxin. Since these compounds have been suggested to differentially
      block voltage-dependent inhibition, relative to voltage-independent, we
      investigated whether the apparent voltage-independent component of Ca(2+) channel
      modulation by 5-hydroxytryptamine (5-HT) shares the same mechanism as the voltage
      dependent component. N-ethylmaleimide inhibited the response to 5-HT by about 50%
      but had no effect on the response to GTP-gamma-S. In dorsal raphe neurons 28.9%
      of the total response to 5-HT was voltage-independent. N-ethylmaleimide had
      identical effects on the voltage-dependent and -independent components as
      measured by tail current inhibition. The response to 5-HT was completely
      sensitive to pertussis toxin, and completely uncoupling the receptors and G
      proteins did not affect the maximal response to GTP-gamma-S. Our results suggest
      that the apparent voltage-independent component of Ca(2+) channel modulation by 5
      HT in dorsal raphe neurons might share the same mechanism as does the voltage
      dependent component. In addition, these experiments provided evidence that
      partial or even complete uncoupling of receptors and G-proteins did not affect
      Ca(2+) current modulation by direct activators of G-proteins.

PMID- 11955724
TI  - Nerve injury-induced changes in opioid modulation of wide dynamic range dorsal
      column nuclei neurones.
AB  - In the present study we investigated the effects of spinal morphine on the
      electrically and naturally evoked responses of gracile nuclei neurones in a rat
      model of neuropathy, induced by the tight ligation of lumbar L5/6 spinal nerves.
      Two weeks after surgery, animals were prepared for electrophysiological
      recordings and neuronal responses were characterised to a range of controlled
      natural (brush, low- and high-intensity von Frey filaments, heat 45 degrees C)
      and peripheral electrical stimuli. Morphine (0.1, 0.25, 1 and 5 microg) was
      applied spinally and its effect was compared to that in sham-operated or naive
      animals. Following surgery, all neuropathic rats exhibited signs of mechanical
      allodynia. Nerve injury induced a significant increase in the receptive field
      size of gracile nuclei neurones, and also produced a non-significant increase in
      the proportion and level of spontaneous activity in these neurones. The baseline
      electrical and natural evoked responses remained unaltered. Spinal morphine
      reduced both the Adelta-fibre- and C-fibre-evoked responses of gracile nuclei
      neurones, and similarly inhibited the heat-evoked responses of neuropathic, sham
      operated and naive rats. Morphine, however, produced only minor reductions (<30%
      inhibition of pre-drug control responses) of the Abeta-fibre- and brush-evoked
      responses of gracile nuclei neurones. These drug effects were similar in all
      animal groups. In complete contrast, morphine produced a marked inhibition of the
      low-intensity punctate mechanical evoked responses (von Freys 2 and 9 g) after
      nerve injury, an effect that was totally lacking in the sham-operated or naive
      animal groups. This dramatic shift was selective for the low-intensity punctate
      mechanical stimuli and such an effect was not seen with the noxious mechanical
      punctate stimulus (von Frey 75 g) where there was a modest inhibition in all
      groups. Our results suggest that there is plasticity in the opioid modulation of
      dorsal column projection pathways following spinal nerve ligation and these
      alterations appear to interact with sensory pathways conveying low-threshold
      punctate stimuli.

PMID- 11955726
TI  - Is uniform target dose possible in IMRT plans in the head and neck?
AB  - PURPOSE: Various published reports involving intensity-modulated radiotherapy
      (IMRT) plans developed using automated optimization (inverse planning) have
      demonstrated highly conformal plans. These reported conformal IMRT plans involve
      significant target dose inhomogeneity, including both overdosage and underdosage
      within the target volume. In this study, we demonstrate the development of
      optimized beamlet IMRT plans that satisfy rigorous dose homogeneity requirements
      for all target volumes (e.g., +/-5%), while also sparing the parotids and other
      normal structures. METHODS AND MATERIALS: The treatment plans of 15 patients with
      oropharyngeal cancer who were previously treated with forward-planned
      multisegmental IMRT were planned again using an automated optimization system
      developed in-house. The optimization system allows for variable sized beamlets
      computed using a three-dimensional convolution/superposition dose calculation and
      flexible cost functions derived from combinations of clinically relevant factors
      (costlets) that can include dose, dose-volume, and biologic model-based costlets.
      The current study compared optimized IMRT plans designed to treat the various
      planning target volumes to doses of 66, 60, and 54 Gy with varying target dose
      homogeneity while using a flexible optimization cost function to minimize the
      dose to the parotids, spinal cord, oral cavity, brainstem, submandibular nodes,
      and other structures. RESULTS: In all cases, target dose uniformity was achieved
      through steeply varying dose-based costs. Differences in clinical plan evaluation
      metrics were evaluated for individual cases (eight different target homogeneity
      costlets), and for the entire cohort of plans. Highly conformal plans were
      achieved, with significant sparing of both the contralateral and ipsilateral
      parotid glands. As the homogeneity of the target dose distributions was allowed
      to decrease, increased sparing of the parotids (and other normal tissues) may be
      achieved. However, it was shown that relatively few patients would benefit from
      the use of increased target inhomogeneity, because the range of improvement in
      the parotid dose is relatively limited. Hot spots in the target volumes are shown
      to be unnecessary and do not assist in normal tissue sparing. CONCLUSION: Sparing
      of both parotids in patients receiving bilateral neck radiation can be achieved
      without compromising strict target dose homogeneity criteria. The geometry of the
      normal tissue and target anatomy are shown to be the major factor necessary to
      predict the parotid sparing that will be possible for any particular case.

PMID- 11955727
TI  - A phase III comparison of radiation therapy with or without recombinant beta
      interferon for poor-risk patients with locally advanced non-small-cell lung
      cancer (RTOG 93-04).
AB  - PURPOSE: The results of Phase I/II data testing beta-interferon with radiation
      therapy in a non-small-cell lung cancer population were promising. Based on these
      data, the Radiation Therapy Oncology Group (RTOG) initiated a Phase III trial to
      test the efficacy of beta-interferon in poor-risk patients with Stages IIIA and
      IIIB non-small-cell lung carcinoma. METHODS: Between September 1994 and March
      1998, 123 patients were accrued to this trial. Enrolled patients were not
      eligible for other chemoradiation studies within the RTOG. Eligibility criteria
      included histologically confirmed Stage IIIA or IIIB non-small-cell lung cancer
      (according to American Joint Committee on Cancer) considered clinically
      inoperable or unresectable at the time of surgery. Patients were required to have
      a Karnofsky performance status 50-70 or >70 and at least 5% weight loss over the
      preceding 3 months. Betaseron (recombinant human interferon beta(ser), rHuIFN
      beta(ser),) was the chosen preparation of beta-interferon. The patients
      randomized to the investigational arm received 16 x 10(6) IU of Betaseron by i.v.
      bolus given 3 days a week (Monday-Wednesday) on Weeks 1, 3, and 5. The Betaseron
      was given 30 minutes before radiation therapy for a total of nine doses.
      Irradiation was delivered at 2 Gy per fraction, 5 days a week, for a total of 60
      Gy over 6 weeks and was identical for both arms. The primary end point of the
      trial was overall survival with local control as a secondary end point.
      Toxicities occurring within 90 days of therapy completion were defined as acute.
      RESULTS: The median follow-up was 4 years (range: 2.5-6 years) for surviving
      patients. Seventy-six percent of all patients completed beta-interferon. Toxicity
      was the primary reason for noncompliance. Radiotherapy (RT) compliance was
      excellent in the RT-alone arm, with 94% completing therapy, compared to 82% in
      the beta-interferon arm (p = 0.0475). Grade 3 and 4 acute toxicities were higher
      on the beta-interferon arm (p = 0.0249). Grade 3 and 4 acute toxicities were
      primarily related to lung (n = 8) and esophagus (n = 7). No Grade 4 or 5 late
      toxicities were seen for patients in the radiation-alone arm. However, three
      patients on the beta-interferon arm experienced Grade 4 toxicity, and one patient
      died. The 1-year survival rate for the RT-alone arm was 44% with a median
      survival time of 9.5 months. The 1-year survival on the beta-interferon arm was
      42% with a median survival of 10.3 months. There was no statistical difference in
      survival times (p = 0.66). CONCLUSIONS: This multicenter, controlled Phase III
      trial failed to confirm the efficacy of Betaseron in patients receiving
      definitive radiotherapy for locally advanced, nonmetastatic non-small-cell lung
      cancer. The use of beta-interferon led to greater rates of both acute and late
      treatment-related toxicity. The RTOG continues to investigate other biologic
      modifiers that may provide a nontoxic alternative for this poor-risk population.

PMID- 11955728
TI  - Supportive use of megestrol acetate (Megace) with head/neck and lung cancer
      patients receiving radiation therapy.
AB  - PURPOSE: The purpose of this study was to measure the effect of megestrol acetate
      (MA) on weight loss and quality of life (QOL) in patients with cancer of the lung
      or head and neck undergoing curative radiation therapy. METHODS AND MATERIALS:
      This was a Phase III, placebo-controlled, double-blind randomized study. Patients
      received either 800 mg/day of MA (20 milliliters po qAM) or placebo over a 12
      week period. Patients received radiation of the head and neck or thorax using a
      dose of at least 50 Gy, either alone or with chemotherapy. Weight was assessed
      weekly, whereas QOL was assessed at baseline and at 4, 8, and 12 weeks. RESULTS:
      Patient characteristics on the MA arm (16 lung, 12 head/neck; mean age: 60 years)
      were similar to those on the placebo arm (17 lung, 11 head/neck; mean age: 65.8
      years). Patients in the MA group had a mean weight loss over 12 weeks of 2.7
      pounds, whereas the placebo group had a mean weight loss of 10.6 pounds. There
      was a significant time by treatment interaction (p = 0.001), with the difference
      in weight between treatment groups being most pronounced after 6 weeks. Although
      overall QOL was similar in both arms of the study, several QOL subscale items did
      differ significantly. Compared to the placebo-treated patients, head-and-neck
      cancer patients in the MA arm reported the ability to eat as much as they liked
      (p = 0.02 at 12 weeks), and lung cancer patients in the MA arm reported
      significantly better appetite at 4 weeks (p = 0.03) and 8 weeks (p = 0.001).
      CONCLUSION: MA used prophylactically is useful as an appetite stimulant; it can
      help patients maintain weight over the course of curative radiotherapy of the
      head and neck or lung and can improve specific aspects of QOL.

PMID- 11955729
TI  - Chromosomal aberrations induced by chemotherapy and radiotherapy in lymphocytes
      from patients with breast carcinoma.
AB  - PURPOSE: Stable chromosomal aberrations (SCAs) have been found in circulating
      lymphocytes from patients treated for breast carcinoma. Therefore, we tried to
      define their incidence in such patients, to determine an in vitro dose-effect
      relationship, and to correlate these data with clinical parameters. METHODS AND
      MATERIALS: This prospective study included 25 patients who, after surgery,
      underwent either radiotherapy (RT) alone (n = 15) or RT combined with
      chemotherapy (n = 10). SCAs were scored using the fluorescent in situ
      hybridization technique before RT and 4 and 12 months after RT. Dose-effect
      curves were established by in vitro irradiation of blood samples with 2 and 4 Gy,
      before and after treatment. RESULTS: In all patients, the rate of SCAs increased
      significantly after external irradiation. No significant decrease in SCAs was
      observed during the first year after RT. RT and chemotherapy had no effect on the
      lymphocyte in vitro dose-effect relationship. No relationship was found in the
      distribution of patients between the yield of SCAs scored after external
      irradiation and after in vitro irradiation. SCAs after RT or in vitro irradiation
      did not correlate with family history of breast carcinoma or acute toxicity of
      treatment. More significantly, the yield of SCA after external irradiation was
      strongly related to the irradiation of the internal mammary chain and the
      supraclavicular lymph node area, suggesting that the volume of irradiated blood
      vessels was an essential parameter in determining the rate of SCAs. CONCLUSION: A
      high and stable yield of SCAs persisted at least 1 year after external
      irradiation. The nature of the volume irradiated containing large blood vessels
      was the major determinant of the observed biologic dose.

PMID- 11955730
TI  - Early response of lung in breast cancer irradiation: radiologic density changes
      measured by CT and symptomatic radiation pneumonitis.
AB  - PURPOSE: To quantify radiologic changes in the lung with CT after radiotherapy
      (RT) for breast cancer (BC) and to study their association with treatment
      techniques and symptomatic radiation pneumonitis (RP). METHODS AND MATERIALS: CT
      scans of the lungs were performed before and 4 months after RT in 121 BC patients
      treated with four different RT techniques. The changes in mean density (MDCs)
      were analyzed at two lung levels (i.e., the central and apical CT slice). The
      central CT slice was also analyzed with respect to the MDCs in the anterior third
      and anterior half of the ipsilateral lung area. In mastectomized patients who
      received chest wall RT with an en-face electron beam, the maximal depths for a
      range of isodose curves were measured. The occurrence of mild/moderate
      symptomatic RP was assessed prospectively 1, 4, and 7 months after RT. Data on
      covariates with potential confounding effect on RT-induced lung toxicity were
      also collected prospectively. RESULTS: In the entire study population, an
      association between the MDCs in the anterior third of the central CT slice and
      treatment technique (p <0.001) and symptomatic RP (p <0.001) was found. Among
      patients with chest wall treatment consisting of an en-face electron beam, the
      MDCs of the anterior third of the central CT slice correlated with the 35%
      isodose curve (16-30 Gy) (p = 0.046) and age (p <0.001). No association between
      post-RT lung density changes and pre-RT chemotherapy, concurrent tamoxifen
      intake, or smoking habits was found. Among patients treated with locoregional RT,
      an association was found between the MDCs in the anterior third of the central CT
      slice and the incidence of RP. MDCs in the apical CT slice, however, were not
      associated with RP. CONCLUSION: The results imply that short-term post-RT lung
      density changes and symptomatic RP were associated with RT techniques, total
      doses as low as 16-30 Gy, and increasing age. Structural changes in the central
      part of lung appeared to be more important for the development of RP than changes
      in the apex.

PMID- 11955731
TI  - Dose response and latency for radiation-induced fibrosis, edema, and neuropathy
      in breast cancer patients.
AB  - PURPOSE: To study the incidence of various forms of late normal tissue injuries
      to determine the latency and dose-response relationships. METHODS: We
      retrospectively analyzed the clinical records of 150 breast cancer patients
      treated with radiotherapy after mastectomy in the mid to late 1960s. None of the
      patients had received chemotherapy as a part of their primary treatment.
      Radiotherapy was delivered to the parasternal, axillary, and supraclavicular
      lymph node regions. Almost all the patients continued to be checked at regular 3
      month to 1-year intervals at our Oncology Department. Detailed records were
      available for the entire 34 years of the follow-up period. The patients were
      divided into 3 groups. The prescribed dose was either 11 x 4 Gy (treated with
      60Co photons) or 11 x 4 Gy or 14-15 x 3 Gy (treated with both 60Co photons and
      electrons). The dose recalculation at the brachial plexus where the axillary and
      supraclavicular beams overlapped was performed in the early 1970s and expressed
      in cumulative radiation effect (CRE) units. It varied widely among the individual
      patients. The received dose has now been converted to biologic effective dose(3)
      units, and from that into the equivalent dose in 2-Gy fractions to plot the dose
      response relationships. RESULTS: We present a comparison of the latency and
      frequency of fibrosis, edema, brachial plexus neuropathy, and paralysis in the
      three different subgroups and the total group. Dose-response relationships are
      shown at 5, 10, and 30 years after irradiation. CONCLUSION: The use of large
      daily fractions, combined with hotspots from overlapping fields, was the cause of
      the complications. Clear dose-response curves were seen for late radiation
      injuries. The incidence seen at 5 years did not represent the full spectrum of
      injuries. Doses that seem safe at 5 years can lead to serious complications
      later.

PMID- 11955732
TI  - Postmastectomy radiotherapy of the chest wall: dosimetric comparison of common
      techniques.
AB  - PURPOSE: To compare seven techniques for irradiation of the postmastectomy chest
      wall (CW) using normal tissue complication probability (NTCP) predictions for
      pneumonitis and ischemic heart disease and dose-volume histogram analyses for
      normal and target tissues. METHODS AND MATERIALS: Plan comparisons were performed
      for 20 left-sided postmastectomy CW RT cases using target volumes based on
      clinical delineation of standard field borders. Seven common treatment techniques
      were planned for each case, using a prescription of 50 Gy in 25 fractions to the
      CW and internal mammary node (IMN) targets. NTCP model metrics were used to
      quantify the risks of pneumonitis and ischemic heart disease, supplemented by
      dose-volume metrics to assess the target coverage to the CW and IMNs, as well as
      normal tissue dose (lung and heart). RESULTS: Overlap in the distributions of the
      CW mean dose for all plans was found, except cobalt, which was significantly less
      than the remaining techniques (global F test, F = 21.90, p <0.0001). Standard
      tangents produced a significantly lower IMN mean dose than all other methods, as
      expected (F = 59.55, p < 0.0001); the reverse hockey stick and cobalt techniques
      were lower than the other methods, which were statistically similar. Cobalt
      produced a significantly higher percentage of the heart that received >30 Gy
      (V30) than the other methods (F = 49.76, p <0.0001). Use of partially wide
      tangent fields (PWTFs) resulted in the smallest heart V30. Use of cobalt fields
      resulted in a significantly greater NTCP estimate for ischemic heart disease than
      all the remaining techniques (F = 70.39, p <0.0001). Standard tangents resulted
      in a percentage of the lung receiving >20 Gy (V20) significantly less than with
      PWTFs, 30/70 and 20/80 photon/electron mix, and reverse hockey stick techniques.
      NTCP estimates for pneumonitis revealed significantly better results with
      standard tangents (F = 6.57, p <0.0001). CONCLUSION: No one technique studied
      combines the best CW and IMN coverage with minimal lung and heart complication
      probabilities. The choice of technique should be based on clinical discretion and
      the technical expertise available to implement these complex plans. Of the seven
      techniques studied, this analysis supports PWTFs as the most appropriate balance
      of target coverage and normal tissue sparing when irradiating the CW and IMN.

PMID- 11955733
TI  - Sarcoma as a second malignancy after treatment for breast cancer.
AB  - BACKGROUND: Second malignant neoplasms may be a consequence of radiotherapy for
      the treatment of breast cancer. Prior studies evaluating sarcomas as second
      malignant neoplasms in breast cancer patients have been limited by the numbers of
      patients and relatively low incidence of sarcoma. Using data from the
      Surveillance, Epidemiology and End Results registries, we evaluated the influence
      of radiation therapy on the development of subsequent sarcomas in cases with
      primary breast cancer. METHODS: Cases with primary invasive breast cancer (n =
      274,572) were identified in the Surveillance, Epidemiology and End Results Cancer
      Incidence Public-Use Database (1973-1997). The database was then queried to
      determine the cases developing subsequent sarcomas (n = 263). Eighty-seven of
      these cases received radiation therapy, and 176 had no radiation therapy. The
      cumulative incidence of developing secondary sarcoma and the survival post
      developing secondary sarcoma were determined by the Kaplan-Meier method. RESULTS:
      The occurrence of sarcoma was low, regardless of whether cases received or did
      not receive radiation therapy: 3.2 per 1,000 (SE [standard error] = 0.4) and 2.3
      per 1,000 (SE = 0.2) cumulative incidence at 15 years post diagnosis,
      respectively (p = 0.001). Of the sarcomas occurring within the field of
      radiation, angiosarcoma accounted for 56.8%, compared to only 5.7% of
      angiosarcomas occurring in cases not receiving radiotherapy. The cumulative
      incidence of angiosarcoma at 15 years post diagnosis was 0.9 per 1,000 for cases
      receiving radiation (SE = 0.2) and 0.1 per 1,000 for cases not receiving
      radiation (SE < 0.1). Overall survival was poor for cases of sarcoma after breast
      cancer (27-35% at 5 years), but not significantly different between patients
      receiving or not receiving radiation therapy for their primary breast cancer.
      CONCLUSIONS: Radiotherapy in the treatment of breast cancer is associated with an
      increased risk of subsequent sarcoma, but the magnitude of this risk is small.
      Angiosarcoma is significantly more prevalent in cases treated with radiotherapy,
      occurring especially in or adjacent to the radiation field. The small difference
      in risk of subsequent sarcoma for breast cancer patients receiving radiotherapy
      does not supersede the benefit of radiotherapy.

PMID- 11955734
TI  - A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma
      patients.
AB  - PURPOSE: To evaluate the role of adjuvant chemotherapy in locally advanced
      nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III
      trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone
      in patients with advanced NPC. METHODS AND MATERIALS: Between November 1994 and
      March 1999, 157 patients with Stage IV, M(0) (UICC/AJCC, 1992) advanced NPC
      disease were randomized to receive standard radiotherapy, as follows: 35-40
      fractions, 1.8-2.0 Gy/fraction/day, 5 days/week, to a total dose 70-72 Gy with or
      without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m(2) cisplatin,
      2,200 mg/m(2) 5-fluorouracil, and 120 mg/m(2) leucovorin) after RT. Of 157
      patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for
      survival and toxicity analysis. RESULTS: With a median follow-up of 49.5 months,
      the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5%
      (p = 0.5) and 49.5% vs. 54.4% (p = 0.38) for the radiotherapy-alone group and the
      combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox
      regression showed that the hazard rates ratio of combined treatment to RT alone
      was 0.673 (p value = 0.232); the 95% confidence interval was 0.352 and 1.288,
      respectively. Patients who received combined treatment had a lower systemic
      relapse rate than radiotherapy-alone patients, according to relapse pattern
      analysis. The incidence of leukopenia (>or= Grade 3) occurred in 17 out of 819
      (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe
      mucositis (>or= Grade 3). CONCLUSIONS: We conclude that adjuvant chemotherapy
      after RT for patients with advanced NPC has no benefit for overall survival or
      relapse-free survival.

PMID- 11955735
TI  - Results of radiotherapy for primary subglottic squamous cell carcinoma.
AB  - PURPOSE: To retrospectively evaluate the outcome after radical radiotherapy (RT)
      and surgical salvage and assess the risk of late toxicity for patients with
      primary subglottic squamous cell carcinoma treated at our center. METHODS AND
      MATERIALS: Between 1971 and 1996, 43 patients with primary squamous cell
      carcinoma of the subglottis (35 men, 8 women) were treated with radical RT. All
      received megavoltage irradiation, most commonly to a dose of 50-52 Gy in 20
      fractions during 4 weeks (39 patients). The median follow-up was 4.2 years.
      RESULTS: Local control was achieved with RT alone in 24 (56%) of the 43 patients:
      7 of 11 with T1, 8 of 12 with T2, 4 of 8 with T3, and 5 of 12 with T4. The 5-year
      actuarial local relapse-free rate was 52%. Subsequent local control was achieved
      in 11 of the 13 patients with failed RT and attempted surgical salvage, for an
      ultimate local control rate of 81.4% (35 of 43). The 5-year overall and cause
      specific actuarial survival rate was 50.3% and 66.9%, respectively. No patients
      developed Grade 3 or 4 late radiation morbidity. CONCLUSION: These data support
      the use of primary RT in the treatment of patients with primary squamous cell
      carcinoma of the subglottis as an appropriate treatment approach providing an
      option for laryngeal conservation.

PMID- 11955736
TI  - Cumulative interfraction interval analysis of influence of time and interruptions
      on radiotherapy results in oral cancers.
AB  - PURPOSE: To present a new approach to analyze the influence of time and
      interruptions in fractionated radiotherapy, in terms of cumulative interfraction
      intervals (CIFIs), that is, the interval between nonsuccessive fractions of
      radiotherapy. METHODS AND MATERIALS: The subjects were 142 patients with
      epidermoid cancer of the buccal mucosa-gingiva-palate region treated by 60 Gy in
      25 fractions during 5 weeks. The influence of CIFI between the first and sixth,
      eleventh, sixteenth, and twenty-first fractions (CIFI(1-6), CIFI(1-11), CIFI(1
      16), and CIFI(1-21), respectively), as well as overall treatment time on local
      control, was analyzed by Kaplan-Meier calculation of the primary relapse-free
      survival and Mann-Whitney U testing of the difference in various CIFIs between
      the tumors that recurred (recurred group) and those that did not (controlled
      group). RESULTS: Only CIFI(1-11) influenced local control significantly, with the
      5-year primary relapse-free survival rate being 67.9%, 48.4%, and 32.6% in those
      with CIFI(1-11) of <14, 14, and >14 days (p = 0.0181). The median CIFI(1-11) in
      the controlled group was significantly lower than that in the recurred group (14
      days vs. 15 days; p = 0.0037). CONCLUSION: Interruptions during the first 11
      fractions, including planned weekend gaps, decrease the effect of radiotherapy,
      possibly because of successful tumor cell repopulation during the protracted
      interfraction intervals. The analysis of time in terms of CIFI rather than
      overall treatment time appears to be a promising area for research.

PMID- 11955737
TI  - Brachytherapy for T1-T2 floor-of-the-mouth cancers: the Gustave-Roussy Institute
      experience.
AB  - PURPOSE: In a retrospective analysis, we evaluated the Gustave-Roussy Institute's
      experience of locoregional control, survival, and complications of low-dose rate
      brachytherapy for carcinoma of the floor of the mouth. METHODS AND MATERIALS:
      Between 1970 and 1985, 160 patients with previously untreated carcinoma of the
      floor of the mouth received interstitial brachytherapy as definitive treatment.
      Of the 160 patients, 79 (49%) had T1 and 81 (51%) had T2 lesions, and 127 (79%)
      had N0 and 33 (21%) had N1; 84% of tumors arose from the anterior floor of the
      mouth. Brachytherapy was performed with 192Ir wires, according to the Paris
      system rules, followed by neck dissection (T2 or N1) or follow-up (T1N0).
      RESULTS: With a follow-up period of 9-19 years, the observed survival rates were
      89% at 2 years and 76% at 5 years, and the local control rates were 93% in T1 and
      88% in T2 tumors. A low rate of distant metastases was noticed (5%); 31% of
      patients developed a second primary cancer. Severe mucosal necrosis was observed
      in <10% of patients. Any grade of bone necrosis was seen in 18% of cases (only
      2.5% had G3 necrosis). This complication occurred more frequently in patients
      with poor dental status and in those treated without dental protection during
      implantation (p <0.001). CONCLUSION: Radical brachytherapy offers excellent local
      control (89%) and an acceptable rate of complications (<10% severe necrosis) that
      may be significantly decreased with dental care and the use of protective
      devices. The high incidence of second malignancies remains a major concern in
      these patients.

PMID- 11955738
TI  - Radiation dose-volume effects on growth hormone secretion.
AB  - PURPOSE: Growth hormone (GH) deficiency is a known consequence of central nervous
      system irradiation. The relationship between the dose to the hypothalamus and the
      time to onset of clinically significant GH deficiency is unknown. Conformal
      radiotherapy (CRT) techniques allow for a more accurate determination of
      hypothalamic dosimetry. We correlated the dosimetry of the hypothalamus and the
      peak GH value after CRT in children with localized primary brain tumors. METHODS
      AND MATERIALS: The arginine tolerance/L-dopa test was performed before (baseline)
      and repeated 6 and 12 months after CRT in 25 children (median age 4.8 years) with
      ependymoma (n = 15) or low-grade (n = 8) or high-grade (n = 2) astrocytoma. None
      had evidence of GH deficiency (arginine tolerance/L-dopa peak GH level >10 ng/mL
      [10 microg/L]) at baseline. Peak GH levels were modeled as a function of time
      after CRT and volume of the hypothalamus receiving a dose within the specified
      intervals of 0-20 Gy, 20-40 Gy, and 40-60 Gy. The model was used to predict the
      change in the peak GH levels over time (0-12 months) and fit under the assumption
      that the integral effect of irradiation was a linear sum of the products of the
      volume receiving a particular dose and the impact of that dose. RESULTS: The peak
      GH level declined during the 0-12 months after CRT (p < 0.0001). GH deficiency
      was observed in 11 children at 6 months and a total of 20 children at 12 months.
      As expected, the effect of the dose interval 0-20 Gy was smaller than the 20-40
      Gy dose interval; the largest effect was noted with the dose interval 40-60 Gy.
      The peak GH level may be predicted using the following estimating equation within
      the time limit of 0-12 months: GH(t)=Exp[ln(bGH)-(0.00058V(0-20 Gy)+0.00106V(20
      40 Gy)+0.00156V(40-60 Gy))x t], where bGH is the baseline peak GH level, V(0-20
      Gy), V(20-40 Gy), and V(40-60 Gy) is the percent-volume of the hypothalamus
      irradiated from 0 to 20 Gy, 20 to 40 Gy, and 40 to 60 Gy, respectively, and t is
      time after irradiation. When included in the model, the rate of decline in the
      peak GH response also was influenced by hydrocephalus and tumor location.
      CONCLUSION: The peak GH response within 12 months after CRT depends on
      hypothalamic dose-volume effects and may be predicted on the basis of a linear
      model that sums the effects of the entire distribution of dose. The modeled
      effects may be used to optimize radiotherapy and minimize and treat GH
      deficiency.

PMID- 11955739
TI  - 1H-MRS in vivo predicts the early treatment outcome of postoperative radiotherapy
      for malignant gliomas.
AB  - PURPOSE: To analyze prospectively the prognostic significance of 1H magnetic
      resonance spectroscopy (MRS) in vivo recorded from the tumor bed of patients
      after surgery for malignant glioma. METHODS AND MATERIALS: Fifty-one patients
      aged 20-68 years were examined using a MRI/MRS system (Elscint 2T Prestige). Of
      the 51 patients, 33 had Grade 3 gliomas and 18 had glioblastomas. MRI-localized
      1HMR spectra were acquired using a single-voxel, double-spin-echo sequence.
      Relative intensities of the signals (choline, creatine [Cr] N-acetyl aspartate
      [NAA], myo-inositol, lactate, and lipids) were obtained by numeric integration of
      fitted signals. Two voxels were examined, one located at the tumor bed and the
      second distant to the tumor bed. All patients were irradiated to 60 Gy using
      three-dimensional conformal noncoplanar techniques to 60 Gy. RESULTS: MRS in vivo
      in patients after brain tumor surgery revealed a statistically significant
      decrease in the NAA/Cr ratio and increases in the choline/creatine (Cr),
      choline/NAA, and myo-inosytol/Cr ratios. The intensive signals of lactate and
      lipids appeared in spectrum. Survival correlated strongly with tumor grade and
      patient age but the strongest prognostic factor was the lactate/NAA ratio. For
      lactate/NAA values >2.0 (intensive lactate signal) the 1-year survival rate was
      20%, and for lactate/NAA values <2.0, the 1-year survival rate was 85%.
      CONCLUSION: A new diagnostic tool demonstrated ability to distinguish between
      patients with a favorable prognosis and those who will die within 1 year.

PMID- 11955740
TI  - Metastatic melanoma to the brain: prognostic factors after gamma knife
      radiosurgery.
AB  - PURPOSE: To identify important prognostic factors predictive of survival and
      tumor control in patients with metastatic melanoma to the brain who underwent
      gamma knife radiosurgery. METHODS AND MATERIALS: A total of 122 consecutive
      patients with 332 intracranial melanoma metastases underwent gamma knife
      radiosurgery over a 5-year period. Of these, 39 (32%) also received whole-brain
      irradiation (WBI). The median tumor volume was 0.8 cm(3) (range: 0.02-30.20
      cm(3)), and the median prescribed dose was 20 Gy (range: 14-24 Gy). Median follow
      up was 6.8 months. Univariate and multivariate analyses of survival and freedom
      from progression were performed using the following parameters: status of
      systemic disease, intracranial tumor volume, number of lesions, tumor location,
      Karnofsky performance status, gender, age, and WBI. RESULTS: Overall median
      survival was 7.0 months from time of radiosurgery and 9.1 months from the onset
      of brain metastasis. In multivariate analysis, improved survival was noted in
      patients with total intracranial tumor volume <3 cm(3) (p = 0.003) and inactive
      systemic disease (p = 0.0065), whereas other parameters studied were of lesser
      importance (tumor location, p = 0.056, and Karnofsky performance status, p =
      0.086), or of no significance (number of lesions, WBI, age, and gender). Freedom
      from subsequent brain metastasis depended on intracranial tumor volume (p =
      0.0018) and status of systemic disease (p = 0.034). CONCLUSIONS: Stereotactic
      radiosurgery is an effective treatment modality for patients with intracranial
      metastatic melanoma. Tumor volume and status of systemic disease are good
      independent predictors of survival and freedom from tumor progression.

PMID- 11955741
TI  - Retreatment of the spinal cord with palliative radiotherapy.
AB  - PURPOSE: We conducted this retrospective review of patients whose spinal cord was
      irradiated twice to evaluate the outcome in terms of palliation and long-term
      side effects. METHODS AND MATERIALS: Eight patients (4 females, 4 males; median
      age: 67 years) were identified whose spinal cord had been irradiated twice
      between July 1990 and July 1997, usually for the management of bone metastases.
      All patients were followed up until their death from progressive disease. The
      Karnofsky performance score at the time of retreatment ranged from 20% to 90%.
      Total dose for the first treatment ranged from 29 to 50 Gy (median: 38 Gy) with
      single doses 1.25-3 Gy; the total dose for the retreatment ranged from 29 to 38
      Gy (median: 30 Gy) with a single dose 1.8-4 Gy. The cumulative dose ranged from
      59 to 88 Gy (median: 67.5 Gy). The overlap in the site of retreatment consisted
      of 1-3 segments, whereas in one patient, 2 single segments were treated twice.
      The outcome in terms of progressive disease, the palliative effects, and the
      development of myelopathy was assessed retrospectively. RESULTS: The median
      interval to reirradiation was 30 months (range: 6-63 months), and the median
      follow-up after the last treatment was 16 months (range: 5-44 months). After
      reirradiation, 4/7 patients experienced complete pain relief, 2/7 patients
      experienced minor pain relief, and only 1 patient showed no change. Two patients
      with paraparesis experienced complete recovery. All patients tolerated
      retreatment very well. No serious acute side effects requiring any therapy were
      seen. During follow-up, no patient showed treatment-induced neurologic
      abnormalities affecting motor and sensory function, and all patients were able to
      walk and were continent for stool and urine. CONCLUSION: On the basis of the
      findings in this limited number of patients, it is not possible to give clear and
      general recommendations concerning the optimal total dose and fraction size that
      will have maximal palliative effects and minimal side effects. However, for the
      purpose of palliation, retreatment within the dose range used at our institution
      should be considered, taking the patient's expected life span and clinical
      symptoms into account.

PMID- 11955742
TI  - Is the therapeutic index better with gemcitabine-based chemoradiation than with 5
      fluorouracil-based chemoradiation in locally advanced pancreatic cancer?
AB  - PURPOSE: To retrospectively compare the toxicity and efficacy of concurrent
      gemcitabine-based chemoradiation with that of concurrent 5-fluorouracil (5-FU)
      based chemoradiation in patients with unresectable pancreatic cancer. PATIENTS
      AND METHODS: Between September 1996 and May 2000, 114 patients with localized
      unresectable adenocarcinoma of the pancreas were treated with concurrent
      chemoradiation. Locally advanced unresectable disease was defined as low-density
      tumor in contact with the superior mesenteric artery (SMA) or celiac artery, or
      occlusion of the superior mesenteric-portal venous confluence. Fifty-three
      patients were selected to receive gemcitabine in 7 weekly cycles (250-500
      mg/m(2)) with concurrent radiotherapy (median dose 30 Gy, range 30-33 Gy in 10-11
      fractions). The remaining 61 patients received continuous-infusion 5-FU (200-300
      mg/m(2)) with concurrent radiotherapy (30 Gy in 10 fractions). Radiotherapy was
      delivered to the primary tumor and regional lymphatics. Patients receiving
      gemcitabine and those receiving 5-FU had a similar mean Karnofsky performance
      status (KPS, 89% vs. 86%), distribution of tumor grade (43% vs. 33% poorly
      differentiated), and percent weight loss (all p = NS). However, patients treated
      with gemcitabine had a significantly larger median maximum cross-sectional tumor
      area (TA, 8.8 cm(2) vs. 5.7 cm(2), p = 0.046) and were significantly younger
      (median age 60 vs. 68 years, p <0.001). Severe acute toxicity (ST) was defined as
      toxicity requiring a hospital stay of more than 5 days, mucosal ulceration with
      bleeding, more than 3 dose deletions of gemcitabine or discontinuation of 5-FU,
      or toxicity resulting in surgical intervention or death. Kaplan-Meier analysis
      was used to calculate the actuarial rate of local progression on imaging (LP),
      the rate of distant metastasis (DM), and the overall survival (OS) rate. The
      imaging was reviewed in resected patients. RESULTS: Patients receiving
      gemcitabine developed significantly more ST during treatment (23% vs. 2%, p <
      0.0001) than did those receiving 5-FU. Patients treated with gemcitabine had a
      similar 10-month LP rate (62% vs. 61%), 10-month DM rate (55% vs. 47%), 1-year OS
      rate (42% vs. 28%), and median OS duration (11 months vs. 9 months) to patients
      treated with 5 FU (all p = NS). Five patients who received gemcitabine and 1
      patient who received 5-FU underwent margin-negative pancreaticoduodenectomy after
      chemoradiation. Three patients had a short segment (<or= 1 cm in length) of low
      density tumor abutting the SMA, 1 had involvement of the common hepatic artery,
      and 1 had a short-segment occlusion of the superior mesenteric vein, amenable to
      venous resection and reconstruction. The other patient was thought to have
      inflammatory changes discontiguous with the tumor surrounding the SMA, which
      resolved after therapy. TA >10 cm(2) (p = 0.03) and poor differentiation (p =
      0.07) were associated with a worse survival duration; however, other factors,
      such as KPS and weight loss >10% and age did not influence OS. CONCLUSION:
      Despite the selection of healthier patients to receive gemcitabine, there was a
      significantly higher severe toxicity rate than with 5-FU. The median and 1-year
      survivals were not significantly different with the use of concurrent
      gemcitabine; however, the tumors treated were significantly larger. Additionally,
      a small number of patients with minimal arterial involvement whose disease met
      our radiographic definition of unresectable disease had margin-negative
      resections after treatment with gemcitabine-based chemoradiation. These possible
      benefits and the high rate of severe toxicity define a very narrow therapeutic
      index for concurrent gemcitabine-based chemoradiation given by this schedule of
      administration.

PMID- 11955743
TI  - Organ preservation in patients with invasive bladder cancer: initial results of
      an intensified protocol of transurethral surgery and radiation therapy plus
      concurrent cisplatin and 5-fluorouracil.
AB  - PURPOSE: To assess safety, tolerance, and disease control of transurethral
      resection of the bladder tumor (TURB) plus concurrent cisplatin, 5-fluorouracil
      (5-FU), and radiation therapy (RT) with selective organ preservation in patients
      with bladder cancer. PATIENTS AND METHODS: Forty-five patients with muscle
      invading or high-risk T1 (G3, associated carcinoma in situ, multifocality, >5 cm)
      bladder cancer were entered into a protocol of TURB followed by concurrent
      cisplatin (20 mg/m(2)/day, 20-min infusion) and 5-FU (600 mg/m(2)/day, 120-hour
      continuous infusion), administered on Day 1-5 and 29-33 of RT (single dose 1.8
      Gy, total dose to the bladder 54-59.4 Gy). Response was evaluated by restaging
      TURB 6 weeks later. In case of invasive residual or recurrent tumor, salvage
      cystectomy was recommended. Median follow-up was 35 months (range: 8-80 months).
      RESULTS: Thirty-nine patients (87%) had no detectable tumor at restaging TURB; 29
      patients (64%) have been continuously free of tumor in their bladders. A
      superficial relapse occurred in 4 patients, a muscle-invasive relapse in 6
      patients. Overall survival and survival with preserved bladder was 67% and 54%,
      respectively, at 5 years. Hematologic Grade 3/4 toxicity occurred in 10%/4%;
      Grade 3 diarrhea occurred in 9%. Thirty-four patients (76%) completed the
      protocol as scheduled or with only minor deviations. One patient required salvage
      cystectomy because of a shrinking bladder. CONCLUSION: This protocol of
      concurrent cisplatin/5-FU and RT has been associated with acceptable toxicity.
      The complete response rate of 87% and the 5-year survival with intact bladder of
      54% are encouraging and compare favorably with our historical control series
      using RT with carboplatin and cisplatin alone.

PMID- 11955744
TI  - Practice patterns for prostate cancer in nine central and northern Italy
      radiation oncology centers: a survey including 1759 patients treated during two
      decades (1980-1998).
AB  - PURPOSE: Prostate cancer patients in Italy are offered the choice of the full
      spectrum of possible treatment options for their disease, but the diffusion of
      the more recent technological refinements among the Radiation Oncology centers is
      not homogeneous and there is a need to establish a reference "historical" data
      source. This retrospective study describes the changing patterns in prostate
      cancer patient practice and the therapeutic results obtained in nine Radiation
      Oncology centers of Northern and Central Italy (five in Northern Italy and four
      in Central Italy). METHODS AND MATERIALS: A total of 1759 prostate cancer
      patients, radically treated in the nine radiotherapy (RT) centers between 1980
      and 1998, made up the study population. Data collected for each patient included
      clinical, pathologic, therapeutic features, and toxicity. The overall survival,
      disease-specific survival (DSS), and clinical relapse-free survival (RFS) were
      calculated for the whole series and for the subsets of patients defined by
      different clinical, pathologic, and therapeutic features, according to three
      accrual periods (A, 1980-1990; B, 1991-1994; and C, 1995-1998). Univariate and
      multivariate analyses were performed to identify prognostic factors related to
      survival and late adverse effects (cystitis and proctitis) probability. RESULTS:
      Patient accrual increased markedly during the 2 decades considered, and the
      percentage of cases with Stage C or D disease dropped from 49% (period A) to 43%
      (period B) to 37% (period C) (p < 0.0001, chi-square). The baseline prostate
      specific antigen value was available for 10%, 76%, and 95% of the cases treated
      in the three different periods. The major changes in the therapeutic options were
      an increase in dose to the prostate (>66 Gy in 44%, 84%, and 93% of the patients
      treated in period A, B, and C, respectively); a reduction in treated volumes,
      including pelvic lymphatic drainage (56-39% before 1995, 22% thereafter); and an
      increase in cases treated in association with hormonal therapy (50% before 1991,
      80% thereafter). Lower energy (<10 MV) photon beams were progressively abandoned
      (12% before 1990 vs. 6-7% thereafter), along with an increase in the use of
      blocks (60% in the last 4 years of the study vs. about 30-40% before 1995) and
      "conformal" RT (applied in 41% of cases treated after 1994). The actuarial RFS,
      DSS, and overall survival rate at 5 years was, respectively, 60% +/- 2%, 75% +/-
      2%, 66% +/- 2% for period A; 74% +/- 2%, 90% +/- 1%, 83% +/- 2%, for period B;
      and 67% +/- 5%, 90% +/- 2%, 79% +/- 5% for period C. The actuarial overall
      survival, DSS, and RFS rate for the whole series of 1759 patients was 77% +/- 1%,
      86% +/- 1%, and 68% +/- 1% at 5 years, respectively. Multivariate analysis showed
      that only American Urologic Association stage, grade, dose to the prostate,
      accrual period, association with hormonal treatment after (or both after and
      before) RT (only in terms of DSS and RFS), and baseline prostate-specific antigen
      value (only for RFS) retained prognostic significance in the final Cox model.
      CONCLUSION: The increase in the accrual of prostate cancer patients radically
      treated with RT has been accompanied by considerable changes in the clinical
      features at presentation, as well as in the staging and treatment procedures.
      Patients treated more recently had better survival results. An earlier stage and
      more favorable grade were linked with better overall, DSS, and RFS at
      multivariate analysis. Lower prostate-specific antigen baseline values were also
      related to better RFS. Better results were obtained with higher radiation doses,
      and the dose to tumor seemed the most important treatment-related prognostic
      factor. The toxicity (cystitis and proctitis, every Radiation Therapy Oncology
      Group grade) was substantially the same in the different accrual periods, but
      larger treated volumes and higher doses appeared to increase the incidence of
      late effects.

PMID- 11955746
TI  - Intensity-modulated whole pelvic radiotherapy in women with gynecologic
      malignancies.
AB  - PURPOSE: To describe our initial clinical experience with intensity-modulated
      whole pelvic radiotherapy (IM-WPRT) in women with gynecologic malignancies.
      METHODS AND MATERIALS: Between February 2000 and August 2001, 40 gynecology
      patients underwent IM-WPRT. After fabrication of customized immobilization, all
      patients underwent contrast-enhanced CT, and a clinical target volume was
      contoured consisting of the upper vagina, parametria, uterus (if present), and
      presacral and pelvic lymph node regions. The clinical target volume was expanded
      by 1 cm to create a planning target volume (PTV). Using commercially available
      software, 7- or 9-field, 6-MV, coplanar IM-WPRT plans were generated for all
      patients. The worst acute gastrointestinal and genitourinary toxicity during
      treatment was scored on a 4-point scale: 0, none; 1, mild, no medications
      required; 2, moderate, medications required; and 3, severe, treatment breaks or
      cessation, hospitalization. As a comparison, acute toxicities in 35 previously
      treated conventional WPRT patients were analyzed. No significant differences were
      noted in the clinicopathologic and treatment factors between the two groups.
      RESULTS: IM-WPRT plans provided excellent PTV coverage, with considerable sparing
      of the surrounding normal tissues. On average, 98.1% of the PTV received the
      prescription dose. The average percentage of the PTV receiving 110% and 115% of
      the prescription dose was 9.8% and 0.2%, respectively. IM-WPRT was well
      tolerated, with no patient developing Grade 3 toxicity. Grade 2 acute
      gastrointestinal toxicity was less common in the IM-WPRT group (60 vs. 91%, p =
      0.002) than in the conventional WPRT group. Moreover, the percentage of IM-WPRT
      and WPRT patients requiring no or only infrequent antidiarrheal medications was
      75% and 34%, respectively (p = 0.001). Although less Grade 2 genitourinary
      toxicity was seen in the IM-WPRT group (10% vs. 20%), this difference was not
      statistically significant (p = 0.22). CONCLUSION: IM-WPRT is a promising approach
      in gynecology patients. IMRT planning resulted in excellent PTV coverage, with
      considerable sparing of normal tissues. Treatment was well tolerated and
      associated with less acute gastrointestinal sequelae than conventional WPRT.
      Longer follow-up and more patients are needed, however, to evaluate the full
      merits of this novel approach.

PMID- 11955745
TI  - Is vascular and lymphatic space invasion a main prognostic factor in uterine
      neoplasms with a sarcomatous component? A retrospective study of prognostic
      factors of 60 patients stratified by stages.
AB  - BACKGROUND: Sarcomatous neoplasms of the uterine corpus are still a challenge in
      terms of obtaining prognostic factors and the most optimum complementary
      treatment to surgery. The most important prognostic factor is stage; relapses
      usually appear during the first 2 years, and most patients die within the first 3
      years. We have performed a multivariate study of prognostic factors, stratifying
      patients by stage, to determine their impact on overall survival, disease-free
      survival, local relapse-free survival, and distant metastasis-free survival.
      Special emphasis has been given to vascular and lymphatic space invasion (VLSI).
      METHODS: Sixty patients diagnosed with uterine neoplasms with a main sarcomatous
      component were treated at Hospital Clinic i Universitari of Barcelona between
      January 1975 and June 1999. Pathologic type: 32 carcinosarcomas, 14
      leiomyosarcomas, 9 adenosarcomas, and 5 endometrial stromal sarcomas. TREATMENT:
      58/60 surgery, 35/60 postoperative radiotherapy, 2/60 exclusive chemotherapy, and
      3/60 complementary chemotherapy. FIGO stages: 43 Stage I, 4 Stage II, 11 Stage
      III, and 2 Stage IV. Variables analyzed: age, stage, vascular and lymphatic space
      invasion, myometrial invasion, mitotic index, tumor size,
      unicentricity/multicentricity, necrosis, and radiotherapy. STATISTICS: the S and
      Cox proportional risk models. The partial effect of each risk factor was
      calculated by hazard ratio (HR) with a confidence interval of 95%. RESULTS: Early
      stages: Multivariate analysis showed that tumor size larger than 8 cm and VLSI
      had an impact on overall survival (HR = 4.01 and HR = 24.45, respectively). VLSI
      was present in 23% of the cases. Myometrial invasion greater than 50% had an
      impact on disease-free survival and local relapse-free survival (HR was 9.75 and
      3.20, respectively). VLSI had an impact on distant metastasis-free survival (HR =
      2.92). Advanced stages: VLSI was present in 89% of the cases. Only leiomyosarcoma
      type made the overall survival worse (HR = 10.54). CONCLUSIONS: Vascular and
      lymphatic space invasion was a relevant prognostic factor in our series, with an
      impact on overall survival and distant metastasis-free survival in early stages.
      In advanced stages, VLSI had no impact on survival, but was present in 89% of
      cases. Myometrial invasion >50% had an impact on local relapse. Advanced stages
      had a more aggressive behavior, and there was a higher incidence of poor
      prognostic factors in these stages. Nevertheless, prospective studies are still
      needed on prognostic factors and on the best treatment option.

PMID- 11955747
TI  - Dose optimization of fractionated external radiation and high-dose-rate
      intracavitary brachytherapy for FIGO stage IB uterine cervical carcinoma.
AB  - PURPOSE: To determine the optimal dose combination scheme of external beam
      radiotherapy (EBRT) and high-dose-rate (HDR) intracavitary radiation (ICR) for
      maximizing tumor control while conferring an acceptable late complication rate in
      the treatment of Stage IB uterine cervical cancer. METHODS AND MATERIALS: We
      retrospectively analyzed 162 patients with International Federation of Gynecology
      and Obstetrics (FIGO) Stage IB squamous cell carcinoma of the uterine cervix who
      received definitive RT between May 1979 and December 1990. Before HDR-ICR, all
      patients received EBRT to a total dose of 40-46 Gy (median 45), administered
      during 4-5 weeks to the whole pelvis. HDR-ICR was given 3 times weeks to a total
      dose of 24-51 Gy (median 39) at point A, using a dose of 3 Gy/fraction. Central
      shielding from EBRT was begun after the delivery using 20-45 Gy (median 40) of
      the external dose. The total dose to point A, calculated by adding the EBRT
      biologically effective dose (BED) and the ICR BED to point A, was 74.1-118.1 Gy
      (mean 95.2). The rectal point dose was calculated at the anterior rectal wall at
      the level of the cervical os. The local control rate, survival rate, and late
      complication rate were analyzed according to the irradiation dose and BED.
      RESULTS: The initial complete response rate was 99.4%. The overall 5-year
      survival rate and 5-year disease-free survival rate was 91.1% and 90.9%,
      respectively. The local failure rate was 4.9%, and the distant failure rate was
      4.3%. Late complications were mild and occurred in 23.5% of patients, with 18.5%
      presenting with rectal complications and 4.9% with bladder complications. The
      mean rectal BED (the sum of the external midline BED and the ICR rectal point
      BED) was lower in the patients without rectal complications than in those with
      rectal complications (125.6 Gy vs. 142.7 Gy, p = 0.3210). The late rectal
      complication rate increased when the sum of the external midline BED and the
      rectal BED by ICR was >or=131 Gy (p = 0.1962). However, 5-year survival rates did
      not increase with the external midline BED (p = 0.4093). The late rectal
      complication rate also increased, without a change in the survival rate, when the
      sum of the external midline BED and the ICR point A BED was >90 Gy. CONCLUSION:
      In treating Stage IB carcinoma of the uterine cervix with HDR-ICR, using
      fractions of 3 Gy, it is crucial to keep the point A BED at <or=90 Gy to minimize
      late rectal complications without compromising the survival rate. To achieve this
      goal, appropriate central shielding from EBRT is needed.

PMID- 11955749
TI  - The effect of delayed postoperative irradiation on local control of soft tissue
      sarcomas of the extremity and torso.
AB  - PURPOSE: The impact of delayed adjuvant radiotherapy in patients treated by
      surgical resection for peripheral or torso soft tissue sarcoma has not been well
      characterized. We retrospectively examined this issue in an institutional patient
      cohort. METHODS AND MATERIALS: One hundred two adult patients were treated at the
      University of Washington Medical Center between 1981 and 1998 with postoperative
      radiotherapy for cure of a newly diagnosed soft tissue sarcoma. Of this group, 58
      patients had primary intermediate- or high-grade disease of the extremity or
      torso (50 extremity/8 torso). Tumor histology was predominantly malignant
      fibrohistiocytoma, synovial cell sarcoma, and leiomyosarcoma. The group was
      dichotomized according to time interval from definitive resection to the start of
      adjuvant radiation. Twenty-six patients had a short delay, defined as <4 months,
      and 32 patients had a long delay of >or=4 months. Both groups were balanced with
      regard to site, size, margin status, and tumor depth; however, the long-delay
      group had a larger proportion of high histologic grade lesions and was treated
      more frequently with chemotherapy (31/32 [97%] for long-delay patients vs. 14/26
      [54%] for short-delay patients). Median follow-up was 49.5 months (range: 7-113
      months). Median follow-up for patients still alive was 54 months (range: 9-113
      months). Survival outcomes were estimated by the Kaplan-Meier method. RESULTS:
      Overall local relapse-free survival at 5 years from the time of definitive
      resection was 74%. On univariate analysis, estimated 5-year local relapse-free
      survival was significantly improved in the short-delay group (88% vs. 62% for the
      long-delay group, p = 0.048 by log rank). Overall distant relapse-free survival,
      disease-free survival, and overall survival at 5 years were 77%, 68%, and 86%,
      respectively. These survival outcomes were statistically equivalent in both
      radiation delay groups. There was no evidence to suggest that delaying adjuvant
      systemic therapy for postoperative radiation negatively impacted distant relapse
      free survival, disease-free survival, or overall survival. Patterns of failure
      analysis revealed that 11/12 disease failures in the long-delay group had a local
      component, with five patients presenting with solitary local recurrences. Severe
      chronic radiation-related soft tissue or peripheral nerve morbidity was
      infrequent (5/58 or 8.6%) and similar in both groups. CONCLUSIONS: Postoperative
      radiation delays of 4 months or greater were associated with inferior local
      disease control for intermediate- and high-grade soft tissue sarcomas of the
      extremity and torso. Our results suggest that timing postoperative radiation
      before postoperative chemotherapy may optimize local therapy for such patients
      without adversely affecting distant disease control, long-term morbidity, or
      overall survival. Prospective testing of this hypothesis is warranted.

PMID- 11955748
TI  - Human papilloma virus (HPV) DNA associated with prognosis of cervical cancer
      after radiotherapy.
AB  - PURPOSE: The importance of human papilloma virus (HPV) infection in the outcome
      of cervical cancer after radiotherapy remains unknown. Our study explored whether
      the HPV status of tumors is associated with the outcome of radiotherapy in
      patients with cervical cancer. METHODS AND MATERIALS: A total of 84 patients with
      cervical cancer (6 Stage I, 10 Stage II, 49 Stage III, and 19 Stage IV) who
      underwent definitive radiotherapy between January 1995 and June 2000 were
      included in this study. Tumor samples were obtained from all patients by punch
      biopsy before radiotherapy. The presence of HPV and its type were analyzed by
      polymerase chain reaction (PCR) based assay using the consensus primers for E6
      and L1 regions. Actuarial methods were used to calculate overall survival and
      disease-free survival. RESULTS: A total of 42 patients (50%) had cancer
      recurrence after radiotherapy. HPV-positive tumors were found in 76.2% (64 cases)
      of patients. HPV-negative patients survived for significantly shorter time
      periods compared to the HPV-positive patients in the overall survival (p = 0.007)
      and the disease-free survival (p = 0.005). According to multivariate analysis,
      HPV status is a significant predictor of both overall (p = 0.02) and disease-free
      survival time (p = 0.005). CONCLUSION: The results of this study suggest that HPV
      negative patients with cervical carcinoma have a significantly poorer prognosis
      after radiotherapy, and HPV status may be used as a marker to optimize the
      treatment of patients with this type of cancer.

PMID- 11955750
TI  - Does escalation of the apical dose change treatment outcome in beta-radiation of
      posterior choroidal melanomas with 106Ru plaques?
AB  - PURPOSE: To show the results of treating posterior uveal melanomas with 106Ru
      plaque beta-ray radiotherapy and to review and discuss the literature concerning
      the optimal apical dose prescription (100 vs. 160 Gy). METHODS AND MATERIALS:
      Forty-eight patients with uveal melanomas (median height 3.85 mm + 1 mm sclera)
      were treated with ruthenium plaques. The median apical dose was 120 Gy, the
      median scleral dose 546 Gy. RESULTS: After 5.8 years of follow-up, the overall 5
      year survival rate was 90%, the disease specific 5-year survival rate was 92% (3
      patients alive with metastasis). Six percent received a second ruthenium
      application, 10% of the eyes had to be enucleated. Local control was achieved in
      90% of the patients with conservative therapy alone. Central or paracentral
      tumors showed 50% of the pretherapeutic vision after 4 years, and 80% of the
      vision was preserved in those with peripheral tumors. The main side effects were
      mostly an uncomplicated retinopathy (30%); macular degeneration or scarring led
      to poor central vision in 30% of cases. CONCLUSION: Brachytherapy with ruthenium
      applicators is an effective therapy for small- and medium-size posterior uveal
      melanomas. Our results are comparable to other series. The treatment outcome does
      not seem to be capable of improvement by increasing the apical dose. An
      internationally accepted model for defining the dosage in brachytherapy is
      needed.

PMID- 11955751
TI  - Dose-effect relationship for cataract induction after single-dose total body
      irradiation and bone marrow transplantation for acute leukemia.
AB  - PURPOSE: To determine a dose-effect relationship for cataract induction, the
      tissue-specific parameter, alpha/beta, and the rate of repair of sublethal
      damage, mu value, in the linear-quadratic formula have to be known. To obtain
      these parameters for the human eye lens, a large series of patients treated with
      different doses and dose rates is required. The data of patients with acute
      leukemia treated with single-dose total body irradiation (STBI) and bone marrow
      transplantation (BMT) collected by the European Group for Blood and Marrow
      Transplantation were analyzed. METHODS AND MATERIALS: The data of 495 patients
      who underwent BMT for acute leukemia, who had STBI as part of their conditioning
      regimen, were analyzed using the linear-quadratic concept. The end point was the
      incidence of cataract formation after BMT. Of the analyzed patients, 175 were
      registered as having cataracts. Biologic effective doses (BEDs) for different
      sets of values for alpha/beta and mu were calculated for each patient. With Cox
      regression analysis, using the overall chi-square test as the parameter
      evaluating the goodness of fit, alpha/beta and mu values were found. Risk factors
      for cataract induction were the BED of the applied TBI regimen, allogeneic BMT,
      steroid therapy for >14 weeks, and heparin administration. To avoid the influence
      of steroid therapy and heparin on cataract induction, patients who received
      steroid or heparin treatment were excluded, leaving only the BED as a risk
      factor. Next, the most likely set of alpha/beta and mu values was obtained. With
      this set, the cataract-free survival rates were calculated for specific BED
      intervals, according to the Kaplan-Meier method. From these calculations,
      cataract incidences were obtained as function of the BED at 120 months after
      STBI. RESULTS: The use of BED instead of the TBI dose enabled the incidence of
      cataract formation to be predicted in a reasonably consistent way. With Cox
      regression analysis for all STBI data, a maximal chi-square value was obtained
      for alpha/beta = 1.75 Gy and mu = 0.75 h(-1). When Cox regression analysis was
      applied for patients who had no steroid treatment after BMT, a maximal chi-square
      value was obtained for alpha/beta = 1 Gy and mu = 0.6 h(-1). Cox regression
      analysis was repeated using the data of patients who had not received
      posttransplant steroid treatment and also no heparin administration; we found
      alpha/beta = 0.75 Gy and mu= 0.65 h(-1). An increased cataract incidence was
      observed after steroid treatment of >14 weeks and heparin administration.
      CONCLUSION: The alpha/beta value of 0.75 Gy and mu value of 0.65 h(-1) found for
      the eye lens are characteristic for late-responding tissues. The incidence of
      cataract formation can now be quantified, taking into account the values
      calculated for alpha/beta and mu, TBI dose, and dose rate. Also, the reduction in
      cataract incidence as a result of lens dose reduction by eye shielding can be
      estimated.

PMID- 11955752
TI  - Cataract after total body irradiation and bone marrow transplantation: degree of
      visual impairment.
AB  - PURPOSE: To assess the degree of visual impairment as a result of cataract
      formation after total body irradiation (TBI) for bone marrow transplantation.
      METHODS AND MATERIALS: The data from 93 patients who received TBI in 1 or 2
      fractions as a part of their conditioning regimen for bone marrow transplantation
      were analyzed with respect to the degree of visual impairment as a result of
      cataract formation. The probability to develop severe visual impairment (SVI) was
      determined for all patients, and the degree of visual impairment was assessed for
      56 patients with stabilized cataract, using three categories: no, mild, or
      severe. RESULTS: For all 93 patients, the probability of developing a cataract
      causing SVI was 0.44. For allogeneic patients, it was 0.33 without and 0.71 with
      steroid treatment (p <0.001). All SVI-free probability curves reached a plateau
      distinct from the cataract-free curves. Apparently, cataracts developing late in
      the follow-up period rarely cause SVI. Of the patients with stabilized cataract,
      32% had no visual impairment, 16% had mild, and 52% severe impairment. No or mild
      visual impairment was present in 61% of all patients with stable cataract and no
      steroid treatment compared with only 13% of the patients treated with steroids (p
      = 0.035). CONCLUSION: SVI occurs in only some of the patients (52%) with stable
      cataract after TBI for bone marrow transplantation in 1 or 2 fractions. Steroid
      treatment markedly increases the probability of developing visual problems as
      result of a cataract after TBI.

PMID- 11955753
TI  - Interaction of pemetrexed disodium (ALIMTA, multitargeted antifolate) and
      irradiation in vitro.
AB  - PURPOSE: Pemetrexed disodium (Alimta, multitargeted antifolate, LY231514; Eli
      Lilly and Co., Indianapolis, Indiana) ("pemetrexed") is a new folate
      antimetabolite with significant antitumor activity. Different from classic
      antifolates, pemetrexed inhibits several key enzymes of thymidylate and purine
      synthesis, but a radiosensitizing potential may also be presumed. Therefore, the
      interaction of pemetrexed and ionizing radiation was studied for in vitro
      clonogenic survival of different human tumor cell lines. METHODS AND MATERIALS:
      Human colon (Widr), breast (MCF-7), cervix (Hela), and lung (LXI) carcinoma cells
      from log-phase cultures were exposed to pemetrexed (2 h) in combination with
      different radiation doses given 1 h before pemetrexed washout (all cell lines) or
      at different points of time before or after pemetrexed addition (Widr). Survival
      curves were analyzed according to the linear-quadratic (LQ) model, and mean
      inactivation doses (MID) and radiation enhancement ratios were calculated from
      the survival curve parameters. Cell-cycle progression of serum-stimulated and
      pemetrexed- or mock-treated Widr cells was monitored by flow cytometry. RESULTS:
      Radiosensitization was found for all cell lines at moderately toxic pemetrexed
      exposures (0.05-0.3 microg/ml [106-636 nM]), but this was cell-type dependent and
      was most pronounced at roughly isotoxic concentrations, for the least pemetrexed
      sensitive Widr cells. Enhancement ratios ranged from about 1.2 (MCF-7 and Hela)
      to 1.8 (Widr), with a tendency to increase with pemetrexed concentration. Little,
      if any, change of radiosensitization was observed (Widr) when the time of
      irradiation was varied from 4 h before to 10 h after the beginning of pemetrexed
      treatment. Cell-cycle progression of serum-stimulated Widr cells was only
      marginally affected by pemetrexed. CONCLUSIONS: Pemetrexed enhances radiation
      induced cell inactivation at moderately toxic exposures and over many hours after
      drug removal. This effect is not due to disturbed cell-cycle progression, but
      likely involves an interaction of pemetrexed with long-lived (>4 h) cellular
      radiation damage and needs to be considered when introducing a combined clinical
      application.

PMID- 11955754
TI  - Issues in respiratory motion compensation during external-beam radiotherapy.
AB  - PURPOSE: To investigate how respiration influences the motion of lung and
      pancreas tumors and to relate the observations to treatment procedures intended
      to improve dose alignment by predicting the moving tumor's position from external
      breathing indicators. METHODS AND MATERIALS: Breathing characteristics for five
      healthy subjects were observed by optically tracking the displacement of the
      chest and abdomen, and by measuring tidal air volume with a spirometer.
      Fluoroscopic imaging of five radiotherapy patients detected the motion of lung
      and pancreas tumors synchronously with external breathing indicators. RESULTS:
      The external and fluoroscopic data showed a wide range of behavior in the normal
      breathing pattern and its effects on the position of lung and pancreas tumors.
      This included transient phase shifts between two different external measures of
      breathing that diminished to zero over a period of minutes, modulated phase
      shifts between tumor and chest wall motion, and other complex phenomena.
      CONCLUSIONS: Respiratory compensation strategies that infer tumor position from
      external breathing signals, including methods of beam gating and dynamic beam
      tracking, require three-dimensional knowledge of the tumor's motion trajectory as
      well as the ability to detect and adapt to transient and continuously changing
      characteristics of respiratory motion during treatment.

PMID- 11955755
TI  - Applicator-guided intensity-modulated radiation therapy.
AB  - PURPOSE: We are introducing a novel method for delivering highly conformal dose
      distributions to cervical cancer tumors using external beam intensity-modulated
      radiation therapy. The method, termed applicator-guided intensity-modulated
      radiation therapy (AGIMRT), will use an applicator substitute placed in the
      vagina and uterus to provide spatial registration and immobilization of the
      gynecologic organs. The main reason for the applicator substitute will be to
      localize the fornices, cervix, and uterus with the expectation that the other
      nearby organs will also be reproducibly positioned with respect to the applicator
      substitute. Intensity-modulated radiation therapy (IMRT) dose distributions will
      be used as a substitute for high-dose-rate intracavitary brachytherapy
      procedures. The flexibility of IMRT will enable customized dose distributions
      that have the potential to reduce complications and improve local control,
      especially for locally advanced disease. METHODS AND MATERIALS: To test the
      advantages of IMRT over intracavitary brachytherapy, volumetric scans of three
      cervical cancer patients were obtained with implanted CT-compatible applicators.
      IMRT dose distribution simulations using tomotherapy, were compared against
      intracavitary brachytherapy using cesium tubes to investigate the dosimetric
      differences of the two modalities. Because these tumor volumes do not image well
      on CT, the target volumes were defined as the isodose surface containing the
      traditional point A, defined as 2 cm superior to the vaginal fornices and 2 cm
      lateral to the intrauterine canal. One patient had a uterus that wrapped superior
      and anterior to the bladder. For this case, the cervix and uterus were selected
      as the target volume. To determine the potential for using an applicator
      substitute to localize internal organs, the posterior bladder and anterior rectal
      surfaces were localized relative to the colpostats. Comparisons of the colpostat
      localized surfaces were conducted for two scan studies for 3 patients. RESULTS:
      The IMRT distributions covered the point-A isodose surfaces while reducing doses
      to the bladder and rectum. Brachytherapy showed extensive underdose regions in
      the target volume for the wrapped-around target. Spatial positioning was better
      than 0.7 and 1.3 cm in the rectum and bladder, respectively, indicating the
      potential that an applicator substitute may be able to localize these structures.
      CONCLUSIONS: AGIMRT has the potential for improving critical structure avoidance
      while maintaining highly reproducible and accurate internal organ registration
      found with brachytherapy.

PMID- 11955758
TI  - Chemotherapy and altered fractionation in head-and-neck cancer: in regard to
      Staar et al., IJROBP 2001;50:1161-1171.

PMID- 11955756
TI  - Inclusion of geometric uncertainties in treatment plan evaluation.
AB  - PURPOSE: To correctly evaluate realistic treatment plans in terms of absorbed
      dose to the clinical target volume (CTV), equivalent uniform dose (EUD), and
      tumor control probability (TCP) in the presence of execution (random) and
      preparation (systematic) geometric errors. MATERIALS AND METHODS: The dose matrix
      is blurred with all execution errors to estimate the total dose distribution of
      all fractions. To include preparation errors, the CTV is randomly displaced (and
      optionally rotated) many times with respect to its planned position while
      computing the dose, EUD, and TCP for the CTV using the blurred dose matrix.
      Probability distributions of these parameters are computed by combining the
      results with the probability of each particular preparation error. We verified
      the method by comparing it with an analytic solution. Next, idealized and
      realistic prostate plans were tested with varying margins and varying execution
      and preparation error levels. RESULTS: Probability levels for the minimum dose,
      computed with the new method, are within 1% of the analytic solution. The impact
      of rotations depends strongly on the CTV shape. A margin of 10 mm between the CTV
      and planning target volume is adequate for three-field prostate treatments given
      the accuracy level in our department; i.e., the TCP in a population of patients,
      TCP(pop), is reduced by less than 1% due to geometric errors. When reducing the
      margin to 6 mm, the dose must be increased from 80 to 87 Gy to maintain the same
      TCP(pop). Only in regions with a high-dose gradient does such a margin reduction
      lead to a decrease in normal tissue dose for the same TCP(pop). Based on a rough
      correspondence of 84% minimum dose with 98% EUD, a margin recipe was defined. To
      give 90% of patients at least 98% EUD, the planning target volume margin must be
      approximately 2.5 Sigma + 0.7 sigma - 3 mm, where Sigma and sigma are the
      combined standard deviations of the preparation and execution errors. This recipe
      corresponds accurately with 1% TCP(pop) loss for prostate plans with clinically
      reasonable values of Sigma and sigma. CONCLUSION: The new method computes in a
      few minutes the influence of geometric errors on the statistics of target dose
      and TCP(pop) in clinical treatment plans. Too small margins lead to a significant
      loss of TCP(pop) that is difficult to compensate for by dose escalation.

PMID- 11955759
TI  - Considerations for the implementation of target volume protocols in radiation
      therapy: in regard to Craig et al., IJROBP 2001;49:241-250.

PMID- 11955760
TI  - In regard to Nyandoto et al., IJROBP 2001;51:209-212.

PMID- 11955763
TI  - Is the alpha/beta for prostate tumors really low? In regard to Fowler et al.,
      IJROBP 2001;50:1021-1031.

PMID- 11955765
TI  - 10-year biochemical (prostate-specific antigen) control of prostate cancer with
      125I brachytherapy: in regard to Grimm et al., IJROBP 2001;51:31-40.

PMID- 11955768
TI  - The object behind the echo: dolphins (Tursiops truncatus) perceive object shape
      globally through echolocation.
AB  - Two experiments tested a bottlenosed dolphin's ability to match objects across
      echolocation and vision. Matching was tested from echolocation sample to visual
      alternatives (E-V) and from visual sample to echolocation alternatives (V-E). In
      Experiment 1, the dolphin chose a match from among three-alternative objects that
      differed in overall (global) shape, but shared several 'local' features with the
      sample. The dolphin conducted a right-to-left serial nonexhaustive search among
      the alternatives, stopping when a match was encountered. It matched correctly on
      93% of V-E trials and on 99% of E-V trials with completely novel combinations of
      objects despite the presence of many overlapping features. In Experiment 2, a
      fourth alternative was added in the form of a paddle that the dolphin could press
      if it decided that none of the three-alternatives matched the sample. When a
      match was present, the dolphin selected it on 94% of V-E trials and 95% of E-V
      trials. When a match was absent, the dolphin pressed the paddle on 74% and 76%,
      respectively, of V-E and E-V trials. The approximate 25% error rate, which
      consisted of a choice of one of the three non-matching alternatives in lieu of
      the paddle press, increased from right to center to left alternative object,
      reflecting successively later times in the dolphin's search path. A weakening in
      memory for the sample seemed the most likely cause of this error pattern.
      Overall, the results gave strong support to the hypothesis that the echolocating
      dolphin represents an object by its global appearance rather than by local
      features.

PMID- 11955769
TI  - Conditioning the pecking motions of pigeons.
AB  - The spatio-temporal courses of head and neck motions of pigeons while pecking at
      small grains are described. Single and serial pecks are distinguished but the
      inter- and intraindividual variability of the peck kinetics is stressed. Pigeons
      were then trained with instrumental conditioning procedures to speed-up their
      pecking. A partial reinforcement schedule where pigeons had to peck repeatedly
      before receiving reward led to a mild shortening of inter-peck intervals at lower
      reinforcement rates but surprisingly, a lengthening at higher rates. A schedule
      where short inter-peck intervals were differentially rewarded yielded a
      pronounced abbreviation of the inter-peck intervals, but this was achieved by a
      reduction of the movement path rather than an increase in motion velocity. A
      schedule whereby increased approach velocities were differentially rewarded
      yielded marked movement accelerations. When pigeons were rewarded for diminished
      approach speeds they also showed significant movement decelerations. Finally, it
      is shown that pigeons could learn to reliably abort their peck approach movement
      when a visual stimulus signalling a penalty was occasionally presented during the
      approach movement. The proportion of successful peck interruptions decreased as
      these interruption signals occurred later during the approach phase. It is
      concluded that the pecking of pigeons is neither an innately fixed nor a visually
      ballistic movement. It is instead a multiply controlled and flexibly adaptable
      response pattern.

PMID- 11955771
TI  - Attention and time estimation in 5- and 8-year-old children: a dual-task
      procedure.
AB  - This experiment tested the effect of a dual-task on time reproduction in 5- and 8
      year-olds. Children had to reproduce a stimulus duration lasting for 6 or 12 s,
      during which they either did or did not perform a concurrent non-temporal task
      (i.e. picture naming) both in low (LA) and high (HA) attentional demand
      conditions. The results showed that children reproduced shorter durations in the
      dual-task than in the single-task condition, whatever the duration value used.
      However, this shortening effect was greater in the 5-year-olds than in the 8-year
      olds. Furthermore, in the 5-year-olds, temporal reproductions were significantly
      shorter in both dual-tasks (LA or HA) than in the single-task, whereas, in the 8
      year-olds, differences reached significance only between the HA dual-task and the
      single-task. In the non-temporal task, the proportion of naming errors was also
      greater in the dual-task than in the single-task, especially under high
      attentional demand, but it did not significantly differ between the two age
      groups tested.

PMID- 11955770
TI  - Typology of activity bouts and effect of fearfulness on behaviour in meat-type
      chickens.
AB  - Increased physical exercise is known to prevent leg problems in meat-type
      chickens. Our aims were to study in detail the organisation of general and
      locomotor activity, to determine how physical exercise could be promoted and to
      investigate the effects of tonic immobility (TI) duration on spontaneous
      activity. Chicks were allocated to two groups according to their TI duration at 3
      and 20 days (fearful birds, HF, n=11; non-fearful birds, LF, n=14). The behaviour
      patterns expressed by awake birds were recorded as 'activity bouts'. Activity
      bouts were then classified into five classes according to the most long-lasting
      activity in the bout. The behaviour patterns were similar in both groups. The
      FORAGING class contained long-lasting bouts with high levels of locomotor
      activity which decreased considerably with age, when bouts of EATING and DRINKING
      classes became more and more numerous. Bouts in the PREENING and NONE classes
      contained low activity. In conclusion, the level of activity in home pens was
      poorly related to TI. Categorisation of bouts into five classes is valuable to
      understand the general organisation of activity in chickens. The FORAGING class
      included bouts with high levels of locomotion and it could thus be used as a
      general indicator of activity.

PMID- 11955772
TI  - Behavioural differentiation of rats confronted to a complex diving-for-food
      situation.
AB  - Previous studies have shown that a behavioural differentiation appeared in groups
      of rats subjected to an experimental design in which access to the feeder was
      made difficult. Some rats brought back food pellets to the cage (divers) while
      the others (non-divers) stayed in the sole home cage and obtained food only by
      stealing it from divers. In this study, we elaborated a more complex diving-for
      food device which allowed divers to consume the food in a second cage away from
      non-divers. As a result, the expected lack of suppliers should not allow the
      emergence of the non-diver status. Unexpectedly, our results showed the
      apparition of non-divers and the persistence of divers (divers c1) bringing food
      back to the initial cage. Two new categories of rats appear: individuals which
      consume the food in the second cage where they stay once they have reached it
      (divers c2), or occasionally go back to the initial cage throughout the
      experiment (divers c1c2). Our results show the influence of spatial environment
      on social organization of rats and suggest that social pressure strongly
      determines the emergence of specialized roles in a group.

PMID- 11955773
TI  - How rats process spatiotemporal information in the face of distraction.
AB  - How rats process spatiotemporal information in the face of distraction was
      assessed. Rats were trained on a time-place learning task in which the location
      of food availability depended on the amount of time elapsed since the beginning
      of the training session. In each training session each of four levers provided
      food pellets for 5 min on an intermittent schedule. In probe sessions
      interspersed with the final training sessions, the rats were presented with a
      second highly preferred food source-a piece of cheese-at various times into the
      session. Rats choose the correct lever after the cheese distraction, but it
      appeared that their internal clock had stopped during the cheese consumption
      period. Thus rats' internal clock, like that of pigeons, displays the properties
      of 'stop', 'reset', and 'restart'. Rat-pigeon differences in timing processes may
      be restricted to circadian or time of day timing. Present results also suggest
      that rats process spatial and temporal information separately.

PMID- 11955774
TI  - Does beak coloration of male blackbirds play a role in intra and/or intersexual
      selection?
AB  - In many bird species, males may show brightly coloured traits and variance in
      male mating success may be explained by female preference and/or competition
      between males favouring the most coloured males. Male beak coloration has been
      suggested to play an important role in the pairing pattern of European
      blackbirds. Here, we investigate female preference and male-male interactions in
      relation to male beak coloration in this species. We used a field experiment to
      measure female and male responses toward stuffed decoys showing either of two
      beak coloration representing the extremes of the natural variation from yellow to
      orange. Decoys were situated on the centre of plots and behaviours of males and
      females approaching the decoy were recorded. The total number of males and
      females approaching the decoy did not differ between the two model treatments.
      Similarly, there was no difference in the mean time that males and females spent
      near the decoy. The number of males displaying aggressive postures did not differ
      between treatments and no female adopted a sexual posture. We discuss the
      relevance of our results and potential limitations associated with the
      experimental procedure.

PMID- 11955775
TI  - The role of static features of males in the mate choice behavior of female
      Japanese quail (Coturnix japonica).
AB  - In two experiments, we investigated the mate choice behavior of female Japanese
      quail toward taxidermically-prepared male models. Both experiments consisted of
      four phases: (1) habituation; (2) a pre-test in which two taxidermically-prepared
      models of male birds were presented; (3) observation in which the respective non
      preferred male model was presented either alone or with another stimulus, and (4)
      a post-test in which male models were again presented alone. Results showed that
      focal females increased their preference for a non-preferred male model that they
      had previously observed with a live female (Experiment 1) or with a
      taxidermically-prepared female model (Experiment 2). Two control groups ruled out
      the possibility that focal females were choosing male models either because: (1)
      males were presented with an additional stimulus, or (2) females were choosing an
      area where they observed male models with other females. The findings suggest
      that female quail may utilize static, species-specific features of male
      conspecifics in mate choice.

PMID- 11955776
TI  - Multi-male mating, probability of conception, and litter size in the prairie vole
      (Microtus ochrogaster).
AB  - We conducted a mating experiment in the laboratory using prairie voles, Microtus
      ochrogaster, to document that multi-male mating (MMM) can occur in this
      supposedly monogamous species and to test two hypotheses for the advantages of
      MMM in female mammals. The two hypotheses are that MMM (1) increases the
      probability of pregnancy and (2) increases litter size. We also tested the
      hypothesis that multiple copulations, rather than multiple partners, increases
      litter size and/or probability of pregnancy. Females were given a choice of
      mating with any of three males, each of which was tethered in a separate
      compartment. The mate choice bouts were recorded on videotape. We recorded the
      number of copulations and number of males with which females mated over a 24 h
      period. Litter size and probability of pregnancy were not significantly different
      for females that mated with one, two or three males. Increasing numbers of
      copulations, independent from the number of males, also did not increase litter
      size but did significantly increase the probability of pregnancy. MMM, at least
      in prairie voles, must serve some function other than increasing litter size and
      probability of conception.

PMID- 11955778
TI  - Exudative epidermitis and porcine circovirus-2 infection in a Swedish SPF-herd.
AB  - An outbreak of exudative epidermitis (EE) among piglets in a Swedish SPF-herd
      initiated a survey for indications as to the cause of disease. The herd was
      established by caesarean section and has been closed to all new animal material,
      with the exception of semen for artificial insemination (AI). The study comprised
      serum samples from the SPF-herd over a 10-year period (n=109) and a close
      monitoring of animals in the herd during the period after the EE outbreak. Serum
      samples from conventional boars at the AI-station servicing the herd were also
      included (n=9). All serum samples were tested for antibodies to porcine
      circovirus-2 (PCV-2). In addition, 3-week-old piglets from three litters (n=24)
      farrowed close after the initial EE outbreak were closely monitored for clinical
      signs of skin disease, sampled for Staphylococcus hyicus, tested for antibodies
      to porcine parvovirus and in sequentially collected serum samples tested for
      interferon-alpha (IFN-alpha) and interleukin-6. The PVC-2 serology showed that
      animals in the herd were sero-negative at least until 2 months prior to the EE
      outbreak. During the period close after the EE outbreak the animals showed
      varying levels of antibodies to PCV-2 but all the tested animals had sero
      converted 4 months later. The AI boars were also sero-positive to PCV-2 at the
      time of the EE outbreak. Animals in the SPF-herd remained sero-positive to PCV-2
      during the following 7 years. In the monitored litters, one piglet had clinical
      EE and 15 piglets displayed defined erythemas on the abdomen. Fourteen of the
      piglets also had IFN-alpha in serum on one or more occasions during the study,
      indicating viral activity among the animals. S. hyicus was isolated from all of
      the piglets from the earliest sampling point (3 days of age) and onwards,
      irrespective of clinical signs. PCV-2 was isolated from lymph node tissue
      collected from one of the EE affected pigs.Further, increases in the number of
      stillborn piglets, small litters (<6 piglets) and repeat breeders could be
      correlated to the time of PCV-2 sero-conversion. Coincidence of active viral
      infection and sero-conversion to PCV-2 points to the virus as the cause of the EE
      outbreak and reproductive disturbances.

PMID- 11955780
TI  - DNA sequences coding for the F18 fimbriae and AIDA adhesin are localised on the
      same plasmid in Escherichia coli isolates from piglets.
AB  - The adhesin-involved-in-diffuse-adherence (AIDA) afimbrial adhesin is produced by
      human, but not by animal, Escherichia coli, with the exception of German porcine
      verotoxigenic Escherichia coli (VTEC) [Clin. Diagn. Lab. Immunol. 8 (2001) 143].
      Presence and localisation of DNA sequences (aidA) coding for and production of an
      AIDA adhesin were investigated in a collection of Belgian VTEC and non-VTEC E.
      coli isolated from piglets at weaning time. The 174 isolates were also studied by
      colony hybridisation for the presence of DNA sequences coding for the Stx2e
      verocytotoxin and the F18 fimbrial adhesin (fed): 71 were Stx2+F18+AIDA+, 26 were
      F18+AIDA+, 12 were AIDA+, two were Stx2+AIDA+, and one was Stx2+ only. Fifty-four
      of the 58 (F18+)AIDA+ isolates tested positive in a western blotting assay with
      an immune serum raised against the AIDA protein. Hybridisation with the AIDA gene
      probe on plasmid DNA profiles identified a probe-positive plasmid band in the 10
      AIDA+ and in 24 of the 25 F18+AIDA+ isolates studied. Moreover in F18+AIDA+
      isolates, only one plasmid band hybridised with both F18 and AIDA probes. These
      results confirm the presence of aidA-related genes in not only VTEC, but also non
      VTEC, isolates from piglets and the production of an antigenically AIDA-related
      protein by the majority of probe-positive E. coli. Moreover the plasmid DNA
      hybridisation results suggest a localisation on the same plasmid of the aidA- and
      fed-related DNA sequences.

PMID- 11955779
TI  - Antimicrobial resistance in Salmonella enterica serovars Enteritidis and
      Typhimurium isolated from animals in Korea: comparison of phenotypic and
      genotypic resistance characterization.
AB  - Fourteen and 22 each of Salmonella Enteritidis and Salmonella Typhimurium (S.
      Typhimurium) were isolated from animals from 1983 to 1999 in Korea and tested for
      their antibiotic resistance patterns, phage types and resistance gene patterns.
      S. Typhimurium isolates were highly resistant to streptomycin, sulfisoxazole and
      tetracycline, 95, 95 and 86%, respectively. The incidence of multiple antibiotic
      resistance (resistant to more than two drugs tested) of S. Typhimurium isolates
      was extremely high (100%) comparing to S. Enteritidis isolates (21%). Two of the
      five ACSSuT (ampicillin, chloramphenicol, streptomycin, sulfisoxazole and
      tetracycline) resistant type S. Typhimurium isolates were phage type definitive
      type 104 (DT104). For the detection of resistance related genes in S. Enteritidis
      and S. Typhimurium isolates, particularly ACSSuT type S. Typhimurium, antibiotic
      resistance genes, cmlA/tetR, bla(PSE-1) and bla(TEM), and genus Salmonella
      specific gene, sipB/C, were amplified using four pairs of primers in a hot-start
      multiplex polymerase chain reaction (PCR). Two Korean isolates of S. Typhimurium
      DT104 showed bla(TEM) amplicons instead of bla(PSE-1) for the ampicillin
      resistance and they were susceptible to florfenicol. The multiplex PCR used in
      this study was useful in characterization of multiple drug resistant Salmonella
      isolates, especially ACSSuT type S. Typhimurium, and identification of beta
      lactamase gene distribution among Salmonella isolates.

PMID- 11955781
TI  - The effect of concurrent infections with Pasteurella multocida and Ascaridia
      galli on free range chickens.
AB  - Pasteurella multocida and Ascaridia galli are observed with high prevalences in
      free range chickens in Denmark, but the impact is unknown. A study was carried
      out to examine the interaction between A. galli and P. multocida in chickens and
      the impact on production. Five groups, each with 20 18-week-old Lohmann Brown
      chickens were infected. Group 1 was orally infected with 1000+/-50 embryonated A.
      galli eggs. Group 2 received 10(4) cfu P. multocida intratracheally. Group 3 was
      infected with A. galli and subsequently with P. multocida. Group 4 was infected
      with P. multocida followed by A. galli. Group 5 was the control. The study ran
      for 11 weeks where clinical manifestations, weight gain and egg production were
      recorded. Excretion of P. multocida was determined on individual basis and blood
      smears were made for differential counts. At the end of the study pathological
      lesions and the number of adult worms, larvae and eggs in the faeces were
      recorded. The birds were more severely affected when infected with both pathogens
      compared to single infections with A. galli or P. multocida, respectively. A
      lower weight gain and egg production was observed with dual infections. A. galli
      infection followed by a secondary P. multocida infection resulted in more birds
      with pathological lesions and continued P. multocida excretion. In conclusion a
      negative interaction between A. galli and P. multocida was observed and it is
      postulated that free range chickens are at higher risk of being subjected to
      outbreaks of fowl cholera when they are infected with A. galli.

PMID- 11955782
TI  - A msp1alpha polymerase chain reaction assay for specific detection and
      differentiation of Anaplasma marginale isolates.
AB  - Anaplasma marginale is the causative agent of bovine anaplasmosis, a disease
      which can be protected by vaccination with the less pathogenic Anaplasma species,
      A. centrale. Currently, there is no polymerase chain reaction (PCR) assay
      available which differentiates between different species of Anaplasma or which
      can differentiate isolates of A. marginale within outbreaks and between different
      countries. A molecular test specific for A. marginale would be ideal for the
      identification of Anaplasma species in wild ruminants, as possible reservoirs of
      anaplasmosis, and to differentiate between A. marginale from A. centrale. A PCR
      assay was designed to amplify the major surface protein 1alpha gene of the
      rickettsial bovine pathogen, A. marginale both as an inter- and intra-specific
      test. The test did not amplify A. centrale or A. ovis, and discriminated A.
      marginale by amplifying repeat regions within the msp1alpha gene which vary in
      number between many isolates. The nested A. marginale amplicons varied in size
      from 630 to 1190bp representing one to eight internal repeats. All 22 Australian
      isolates tested amplified a 630bp product (one repeat) in contrast to all 19 non
      Australian isolates tested. Eight sequences from Australian isolates from
      different geographical regions confirmed the conserved nature of the Australian
      A. marginale msp1alpha genes. The Australian 'repeat unit' MSP1a deduced amino
      acid sequence has been designated as Australian type 1. The msp1alpha PCR method
      developed here enabled the amplification and comparison of A. marginale isolates
      originating from North and South America, Africa, Israel and Australia. The
      method is sensitive and specific for A. marginale. Although additional msp1alpha
      products were amplified from at least two Australian isolates, the results
      suggest limited introduction of A. marginale into Australia.

PMID- 11955784
TI  - Changes in the prevalence of rotavirus G and P types in diarrheic calves from the
      Kagoshima prefecture in Japan.
AB  - G8 bovine group A rotavirus was the most predominant serotype in calf diarrheal
      fecal specimens examined between 1995 and 1996 in Japan [Vet. Microbiol. 66
      (1999) 301]. To date, no evidence that G8 was the most predominant in the
      typeable specimens has been observed outside Japan. To investigate whether G8
      continues to be as common as G6 and G10, the incidence of the main serotypes was
      determined in the same area (Kagoshima prefecture) between 1997 and 1998 by
      reverse transcription-polymerase chain reaction. From a total of 104 rotavirus
      positive specimens, we successfully identified G type in 79 (76.0%) and P type in
      71 (68.3%). The combination of G and P types varied periodically; in 1995,
      G10P[11] was most common. The most predominant types changed drastically in 1996,
      and G8 and mixed P types were the most predominant. A dramatic shift of the most
      predominant type occurred again in 1997 when G6P[5] was most common. This
      frequency of G6P[5] also continued in 1998. These results suggest that the
      serotypes prevailing in certain areas change periodically.

PMID- 11955783
TI  - Molecular differentiation between NS1 gene of a field strain Bluetongue virus
      serotype 2 (BTV-2) and NS1 gene of an attenuated BTV-2 vaccine.
AB  - At the end of September 2000, clinical symptoms of Bluetongue appeared in sheep
      flocks of the Balearic Islands (Spain). The presence of the BTV serotype 2 in
      tissue and blood samples of affected animals was confirmed by laboratory
      techniques. A systematic vaccination were carried out in affected areas using a
      live monovalent serotype 2 vaccine available from Onderstepoort laboratory (South
      Africa). In order to perform epidemiological studies, a new method to
      differentiate between the NS1 genes of BTV-2 affecting the Balearic islands and
      that of the Onderstepoort commercial live virus vaccine (monovalent, serotype 2)
      has been developed. This procedure is based on the use of an RT-PCR, followed by
      restriction endonuclease analysis. Epidemiological data of a study carried out in
      the period January-October 2001 using this procedure are included.

PMID- 11955785
TI  - Dietary enzyme and zinc bacitracin reduce colonisation of layer hens by the
      intestinal spirochaete Brachyspira intermedia.
AB  - Brachyspira intermedia strain HB60 was used to experimentally infect 40
      individually caged 22-week-old laying hens. Another 10 control birds were sham
      inoculated with sterile broth. All chickens received an experimental layer diet
      based on wheat. The infected birds were randomly divided into four groups of 10,
      with the diet for each group containing either 50 ppm zinc bacitracin (ZnB), 100
      ppm ZnB, 256 ppm of dietary enzyme (Avizyme), 1302), or no additive. Birds were
      kept for 6 weeks after infection, and faecal excretion of B. intermedia, faecal
      water content, egg numbers, egg weights and body weights were recorded weekly.
      Control birds remained uninfected throughout the experiment. B. intermedia was
      isolated significantly less frequently from the groups of experimentally infected
      birds receiving ZnB at 50 ppm or enzyme than from those receiving 100 ppm ZnB or
      no treatment. Infected birds had a transient increase in faecal water content in
      the week following challenge, but no other significant production differences
      were detected amongst the five groups of birds in subsequent weeks. It was not
      established how the ZnB at 50 ppm and the dietary enzyme reduced the ability of
      the spirochaete to colonise, but it may have been by bringing about changes in
      the intestinal microflora and/or the intestinal microenvironment.

PMID- 11955786
TI  - Comparison of three enzyme-linked immunosorbant assays with the indirect
      immunofluorescent antibody test for the diagnosis of canine infection with
      Ehrlichia canis.
AB  - The aim of this study was to compare three different enzyme-linked immunosorbant
      assays (recombinant major antigenic protein 2 (rMAP2)-ELISA, the Immunocomb
      (Biogal, Israel) and the Snap 3Dx assay (IDEXX Laboratories Inc., USA)) with the
      indirect immunofluorescent antibody test in detecting anti-Ehrlichia canis
      immunoglobulin-G (IgG) antibodies. Samples tested were collected from dogs
      suspected to be naturally infected with E. canis and from experimentally infected
      dogs. When qualitative results (positive/negative) were compared, there was an
      overall agreement of 81% (54/67) between the indirect immunofluorescence antibody
      (IFA) test and the rMAP2-ELISA. An overall agreement of 94% (63/67) was found
      between the IFA test and the Immunocomb, and an overall agreement of 91% (61/67)
      was found between the IFA test and the Snap 3Dx assay. In 50 of 67 (74.6%)
      samples tested, complete agreement in the qualitative results was found in all
      four tests. Sixteen of 17 samples with disagreement in the qualitative results
      were found to have IFA titers of 1:320 or less. The sensitivities and
      specificities of the tests were found to be 0.71 and 0.85 for the rMAP2-ELISA,
      0.86 and 0.98 for the Immunocomb, and 0.71 and 1.00 for the Snap 3Dx assay. The
      tests performed in this study were found to be highly specific in detecting E.
      canis antibodies. Their sensitivity was found to be low with sera having IFA
      titers of < or =1:320, while high with sera having titers greater than 1:320.
      Repeating the serological tests 1-2 weeks after the first antibody assay may
      overcome the sensitivity problem with titers of < or =1:320.

PMID- 11955788
TI  - Introduction. Menopause disorders and other menopause related problems.

PMID- 11955787
TI  - A study of "white spotted kidneys" in cattle.
AB  - A study was performed at an abattoir in Australia, in an attempt to correlate
      focal chronic interstitial nephritis (FCIN) producing the so-called "white
      spotted kidney", with Leptospira spp. and other pathogens in cattle. Samples of
      kidneys, urine and blood were collected immediately after slaughter from 46 two
      year-old heifers, and 72 cows and bulls with gross lesions consistent with FCIN.
      The same samples were also collected from nine heifers and 12 cows with no gross
      kidney lesions. Aqueous humour was also collected from the eye of 17 of the adult
      animals. The sera were processed by a microscopic agglutination test for
      leptospira antibodies, while all the other samples were cultured for Leptospira
      spp. and also processed for routine aerobic and anaerobic culture for other
      pathogens. Sub-samples from all the kidneys were fixed in 10% buffered formalin
      and processed histologically. Antibody titers of 1:400 or higher for Lepstospira
      borgpeterseni serovar hardjo were found in six adult animals with FCIN and in one
      adult animal with no gross kidney changes, while antibody titers of 1:400 to L.
      borgpeterseni serovar tarassovi were found in only one animal with FCIN. L.
      borgpeterseni serovar hardjo was isolated from the urine and kidney of one adult
      animal and from the urine of another adult animal, both with FCIN. No pathogens
      were isolated from any of the other samples. The histological lesions were
      consistent in most cases with FCIN. The results suggest that neither Leptospira
      spp. nor active infection by other bacteria are associated with the so-called
      "white spotted kidneys".

PMID- 11955789
TI  - Depression, menopause and estrogens: is there a correlation?
AB  - Women have a higher incidence of depression than men. The lifetime incidence of
      endogenous depression in women is twice the incidence in males. Because
      depression in the elderly is an important public health concern, an eventual
      correlation between menopause and depression is of practical importance. The
      relevant literature is reviewed. There are suggestive data that estrogen
      deficiency may increase the susceptibility for depression. Furthermore, here is
      suggestive evidence from observational studies and a limited number of
      randomized, controlled trials that estrogen therapy after menopause improves mood
      and cognition. However, the clinical relevance of estrogen administration is
      unproved. There are weak data that estrogens might be considered for mild
      depressive symptoms attributed to hot flushes, sleep disturbances, or other
      climacteric symptoms. No hard data exist to indicate whether estrogen could be
      used as adjunct therapy for other depressive disorders during the menopausal
      transition or postmenopausal period, but newer findings suggest that estrogens
      may improve the effect of serotonin reuptake inhibitors.

PMID- 11955790
TI  - Mental well-being in 5000 women participating in the 'Women-Plus' preventive
      medicine program.
AB  - In the present study, we report on an additive evaluation of mental well-being in
      an established program of preventive medicine including general and gynecologic
      examination, and screening mammography. An easy-to-use questionnaire including 19
      questions was completed by 5247 women. Answers were grouped into mental well
      being, zest for living, sexuality, and self-assessment of psychic disorders. A
      risk score for the presence of major depression was calculated. Women with high
      and intermediate risk for major depression were found in 5.0-7.2% and 15.4-19.8%
      depending on age, respectively. Seven to 9.2% and 19.2-26.5% of women suspected
      themselves to be at a high and intermediate risk for psychic disorders,
      respectively. Deterioration of well-being as well as the risk of developing
      depression is mostly overlooked in a general preventive medicine setting. We
      conclude that problems involving mental well-being seem to affect a significant
      number of women. The incorporation of easy-to-use questionnaires able to screen
      for mental problems to general preventive medicine programs must be strongly
      recommended.

PMID- 11955791
TI  - Affective syndrome during perimenopause.
AB  - Perimenopause is characterized by decreasing levels of estrogens and progesterone
      until gonadal secretion comes to a complete halt. There are still very different
      views and positions on the significance of the menopause. Physical, mental
      vegetative and depressive symptoms during climacteric are different in each
      culture. Currently, there is some controversy as to whether or not there really
      is a rise in actual depression during the perimenopausal phase of woman's life.
      The observations from humans taken together indicate that depressive disorders,
      as defined in ICD-10, do not occur more frequently during perimenopause. In this
      context, the terms subthreshold depression and or subsyndromal depression are
      important, describing depressive symptoms which do not fulfil the complete
      clinical picture of a depressive episode, either because there are not enough
      symptoms or because they are not severe enough. The affected women still suffer,
      but until now not enough studies have been carried out on this particular area.
      In view of the complexity and relevance of the perimenopausal period in a woman's
      life, it is necessary to establish and maintain a network of treatment between
      the family physician, gynecologist, psychiatrist and or psychotherapist, as soon
      as significant depressive symptoms occur.

PMID- 11955792
TI  - Depression, endocrinologically a syndrome of premature aging?

PMID- 11955793
TI  - The impact of testosterone imbalance on depression and women's health.
AB  - Women suffer more often from depression than males, indicating that hormones
      might be involved in the etiology of this disease. Low as well as high
      testosterone (T) levels are related to depression and well-being in women, T
      plasma levels correlate to depression in a parabolic curve: at about 0.4-0.6
      ng/ml plasma free T a minimum of depression is detected. Lower levels are related
      to depression, osteoporosis, declining libido, dyspareunia and an increase in
      total body fat mass. Androgen levels in women decrease continuously to about 50%
      before menopause compared to a 20-year-old women. Androgen levels even decline
      70% within 24 h when women undergo surgical removal of the ovaries. Conventional
      oral contraception or HRT cause a decline in androgens because of higher levels
      of SHBG. Hyperandrogenic states exist, like hirsutism, acne and polycystic ovary
      syndrome. Social research suggests high androgen levels cause aggressive behavior
      in men and women and as a consequence may cause depression. Higher androgen
      values are more pronounced at young ages and before and after delivery of a baby
      and might be responsible for the "baby blues". It was found that depression in
      pubertal girls correlated best with an increase in T levels in contrast to the
      common belief that "environmental factors" during the time of growing up might be
      responsible for emotional "up and downs". T replacement therapy might be useful
      in perimenopausal women suffering from hip obesity, also named gynoid obesity.
      Abdominal obesity in men and women is linked to type 2 diabetes and coronary
      heart diseases. Testosterone replacement therapy in hypoandrogenic postmenopausal
      women might not only protect against obesity but also reduce the risk of
      developing these diseases. Antiandrogenic progestins might be useful for women
      suffering from hyperandrogenic state in peri- and postmenopause. Individual
      dosing schemes balancing side effects and beneficial effects are absolutely
      necessary. Substantial interindividual variability in T plasma values exists,
      making it difficult to utilize them for diagnostic purposes. Therefore a "four
      level-hormone classification scheme" was developed identifying when estradiol (E)
      and T levels are out of balance. (1) Low E-low T levels are correlated with
      osteoporosis, depression, and obesity; (2) high E-low T with obesity, decreased
      libido; (3) high T-low E levels with aggression, depression, increased libido,
      and substance abuse; (4) high E-high T with type II diabetes risk, breast cancer
      and cardiovascular risk. Testosterone delivery systems are needed where
      beneficial and negative effects can be balanced. Any woman diagnosed for
      osteoporosis should be questioned for symptoms of depression.

PMID- 11955794
TI  - Relations of androgens and selected aspects of human behavior.

PMID- 11955795
TI  - Genetic modeling of estrogen metabolism as a risk factor of hormone-dependent
      disorders.
AB  - Estradiol is a pleiotropic hormone, involved in the etiology of a wide variety of
      diseases. Over the last decade individual genetic variability of the estradiol
      metabolism has been described as a significant contributor to disease
      susceptibility with variations depending on ethnic background. Among others,
      genetic variations of genes encoding cytochrome P450 (CYP) enzymes play an
      important role in this regard. Mutant alleles of the CYP 1A1 gene are major
      modulators of lung cancer risk among smokers, mediate gender differences in lung
      cancer susceptibility, and have been associated with an elevated risk for breast,
      prostate, colorectal, and oral squamous cell cancer. Variants of the CYP 1B1 gene
      modulate the risk for prostate, ovarian, lung, and breast cancer. Also, mutations
      in the CYP 1B1 gene are the major genetic determinant of congenital glaucoma.
      Mutant CYP 17 alleles are associated with serum and plasma levels of steroid
      hormones, use of hormone replacement therapy, and endometrial, prostate, and
      breast cancer. Available data indicate that the protective effect of a later age
      at menarche is limited to mutant CYP 17 allele carriers. Among women with the
      Polycystic Ovary (PCO) syndrome, mutant CYP 17 alleles are sufficient to
      aggravate the clinical presentation of the disease. Molecular variants of the CYP
      19 gene are associated with an increased risk for breast cancer, advanced disease
      stage, and tumor aromatase production. Carriage of a mutant catechol-O
      methyltransferase (COMT) allele is associated with breast cancer, neurologic
      disorders such as Parkinson's disease, and modulates behavior among patients with
      schizophrenia, alcoholics and the general population. In summary, the available
      evidence points to estrogen metabolising genes as strong hereditary determinants
      of the susceptibility to benign and malignant conditions.

PMID- 11955796
TI  - IGF-1 in gynaecology and obstetrics: update 2002.
AB  - Recent discoveries on endocrine, paracrine and autocrine involvement of insulin
      like growth factor-1 (IGF-1) in the proliferation of many tissues raised the
      attention of its role in reproduction and in the growth of various cancers as
      well as of benign proliferations. The intention of this article is to focus on
      IGF-1 in the field of gynaecology. Perimenopausal women who exhibit high IGF-1
      and low IGF binding protein (IGFBP) levels, like IGFBG-3, have an increased risk
      of developing breast cancer. A higher risk for cervical, ovarian and endometrial
      cancer is related to high IGF-1 levels in post- and premenopausal women. It has
      been shown that myomas, by far the most common benign uterine tumor in women,
      grow in the presence of IGF-1, in vitro as well as in vivo. Studies show that IGF
      1 is involved in the differentiation of various reproductive tissues, like
      endometrium and ovarian tissues. Patients suffering from polycystic ovary
      syndrome (PCO) frequently show insulin resistance accompanied by an increase of
      IGF-1 in plasma. Plasma IGF-1 levels are higher in cases of severe endometriosis,
      however, in endometriosis and in PCO IGF levels locally in the endometrium are
      reduced, what might explain infertility. Recently, it was shown that IGF
      facilitates the implantation of the human embryo in the endometrium during IVF.
      Implantation is a paradox where different immune systems have to collaborate to
      make implantation and survival of the pregnancy possible. IGF seems to be the
      starter molecule so that the two epithelia can fuse. A disturbance can result in
      complications during pregnancy i.e. spontaneous miscarriage, preeclampsia as well
      as defects of the embryo. Therefore, IGF is a useful marker in successful
      pregnancy as well. A better mechanistic understanding of IGF-1 action on the
      cellular level not only provides more elegant mechanistic explanations for the
      scientist, but the practitioner might find it interesting to utilize its
      diagnostic potential as a marker for various diseases. The relation between
      systemic IGF levels and local tissue IGF-1 levels has not yet been determined for
      all conditions.

PMID- 11955797
TI  - Melatonin deficiencies in women.
AB  - The pineal hormone melatonin is the mediator of external light to physiologic
      adaptation to day and night rhythms, it regulates reproduction in animals but
      attempts to utilize melatonin in women for contraception have failed. Melatonin
      seems to be the natural hormone to facilitate sleep in insomniac patients and
      causes no hang over. When applied together with benzodiazepine it allows
      reduction of benzodiazepine without withdrawal effects. It should be applied 2 h
      before sleeping time in doses between 3 and 5 mg. Melatonin acts via the gamma
      aminobutyric acid- and benzodiazepine receptor explaining its success in
      treatment of seizures in children and in adults. Constant application of
      benzodiazepine reduced the production of natural melatonin in rats, supporting
      the evidence that long-term application of benzodiazepine in humans does not
      restore sleeping habits but reduces natural sleeping habits even more. Low
      melatonin levels were seen in bulimia or neuralgia and in women with
      fibromyalgia; replacement reduced pain, sleeping disorders, and depression in
      fibromyalgia and bulimia. Melatonin profiles are a diagnostic tool to distinguish
      between several forms of depression, like major depression, winter depression
      (SAD), unipolar depression, delayed sleep phase syndrome (DSPS). In patients with
      a major depression success with antidepressants correlated with an increase in
      their melatonin profiles but only patients suffering from DSPS can be
      successfully treated with melatonin. In perimenopausal women melatonin
      administration did produce a change in LH, FSH and thyroid hormones. Some
      oncostatic properties are supported by cell culture work and studies in animals.
      In Nordic countries indigenous people suffer less from breast and prostate
      cancer, winter darkness seems to protect. The supposedly increased melatonin
      levels created the 'melatonin hypothesis'. Epidemiological studies did show that
      blind people indeed have half the rate of breast cancers, supporting the
      hypothesis. Controversial results concerning melatonin and insulin resistance and
      glucose tolerance have been published. In postmenopausal women application of
      melatonin reduced glucose tolerance and insulin sensitivity. Pregnant women
      should avoid melatonin, since its teratogenic effect is not known. Patients
      suffering from non-hormone dependent tumors, like leukemia, should avoid melanin,
      since tumor growth was promoted in animal experiments. It can be expected that
      melatonin will receive wide consideration for treatment of sleeping disturbances,
      jet lag, and fibromyalgia once an oral formulation becomes available in Europe.

PMID- 11955798
TI  - Hormone replacement therapy (HRT) in women after genital cancer.
AB  - Women treated for genital cancer are not only suffering from the disease itself,
      but are in most cases confronted with the side effects of the loss of ovarian
      function. Therefore, it is of utmost importance for the gynecologist, who cares
      for these patients, to strongly consider the benefits and drawbacks of hormone
      replacement therapy (HRT) in these women. Overall, it appears, that in women with
      vulva, vaginal, cervical, ovarian and tubal cancer individually adjusted HRT can
      be employed for the benefit and well-being of these patients considering
      psychosomatic, functional and organic aspects. Patients after endometrial cancer
      should be differentiated according to the stage of the disease. In all cases the
      individual minimal effective dose of HRT should be searched for.

PMID- 11955799
TI  - Fluid bed granulation of a poorly water soluble, low density, micronized drug:
      comparison with high shear granulation.
AB  - A 2(4-1) fractional factorial design was used to evaluate the effect of various
      process variables in fluid bed granulation, on the physico-chemical properties of
      granule and tablet containing a high dose, poorly water soluble, low density, and
      micronized drug. The process variables studied were inlet air temperature, inlet
      air flow, spray rate of the binder solution, and atomization air pressure.
      Tablets with identical composition, weight, size and hardness were also
      manufactured in a high shear granulator and their physical properties were
      determined and compared with those produced by the fluidized bed granulation
      method. Except for the granule size distribution, other physical properties of
      granulations and tablets produced in a fluid bed granulator are independent of
      the selected process variables within the study range. Both atomization air
      pressure and spray rate of the binder solution had strong impact on granule size
      distribution. Irrespective of the process conditions used in the fluid bed
      granulation, granules from this process were more porous, less dense and more
      compressible than the granules from the high shear granulation process.
      Comparable tablet dissolution rates to those prepared by the optimized high shear
      granulation method can be achieved by selecting the appropriate process
      conditions in fluid bed granulation. These results suggest that wet granulation
      tablets of a high dose, poorly water soluble, low density, micronized drug can be
      manufactured using a fluidized bed granulation method, with comparable tablet
      dissolution rates to those produced with an optimized high shear granulation
      method.

PMID- 11955800
TI  - Application of acid-treated yeast cell wall (AYC) as a pharmaceutical additive.
      III. AYC aqueous coating onto granules and film formation mechanism of AYC.
AB  - From the viewpoint of effective utilization of natural resources and development
      of new pharmaceutical materials, acid-treated yeast cell wall (AYC) was prepared
      via a novel approach involving acidification of brewers' yeast cell wall. AYC
      aqueous dispersion containing 5% (w/v) AYC and 0.5% (w/v) glycerol was prepared.
      Subsequently, AYC was coated onto core granules containing acetaminophen (AAP).
      Spray mist size under various spray conditions and viscosity of the AYC aqueous
      dispersion at various AYC concentrations were measured. AYC spray mists were
      optically observed. The surface of AYC cast film and AYC-coated granules were
      observed with a confocal scanning laser microscope. We attempted to show the
      utility of AYC as a novel material for granule coating, following the tablet
      coating in our previous report. In addition, the film formation mechanism of AYC
      was investigated. A smooth surface of the AYC-coated granules was obtained at a
      coating ratio of only 5%, which generally requires approximately 15-30% coating
      against the core granule weight, with no aggregation. These results are
      attributable to the fact that the granules were coated with a large number of
      small mists of AYC and the coating progressed efficiently, and the thin film
      layer of AYC was formed on the granules by mutual tangling of the hydrogel layers
      of AYC polysaccharides. AAP release from AYC-coated granules was obviously rapid,
      suggesting the high utility of AYC as a coating material for the rapidly
      releasing granules.

PMID- 11955801
TI  - Susceptibility of the H2-receptor antagonists cimetidine, famotidine and
      nizatidine, to metabolism by the gastrointestinal microflora.
AB  - The H(2)-receptor antagonist ranitidine has previously been shown to be a
      substrate for colonic bacterial metabolism. The objective of the present study
      was to assess the in vitro stability of the other H(2)-receptor antagonists,
      cimetidine, famotidine and nizatidine, to colonic bacteria. One hundred
      milligrams of each drug were introduced into individual batch culture fermenters
      (100 ml) consisting of buffer medium inoculated with freshly voided human faeces
      (10% w/v). Control experiments, equivalent drug quantities in buffer medium
      without the presence of faeces, were also run in parallel. Samples were removed
      at set time intervals over a 24 h period and were subsequently analysed by HPLC.
      A selection of the samples removed from the fermenters was also subjected to
      analysis by UV spectroscopy and mass spectrometry. Following an initial
      dissolution phase in the fermentation system, a marked decline in nizatidine
      concentration was noted over time with virtually no drug remaining after 12 h,
      thereby suggesting degradation and metabolism of the drug by colonic bacteria. No
      such decline in concentration was noted for cimetidine or famotidine or for any
      of the drugs in the control buffer systems. The metabolic reaction pathway for
      nizatidine was complex, although UV and mass spectrometry analysis indicated that
      metabolism was initiated via cleavage of an N-oxide bond within the molecule.
      These results in combination with those obtained from a previous study indicate
      that of the four commercially available H(2)-receptor antagonists, nizatidine and
      ranitidine are susceptible to metabolism by colonic bacteria, which in turn has
      ramifications for drug delivery and absorption.

PMID- 11955802
TI  - Excipient compatibility study of Hypericum perforatum extract (St. John's wort)
      using similarity metrics to track phytochemical profile changes.
AB  - The formulation of botanical dietary supplements is challenging due to their
      complex activity-composition relationship, as well as physical and chemical
      stability issues. As excipient compatibility testing is a major component of
      sound formulation development, the objectives of this work were: (1) explore
      excipient compatibility storage paradigms; (2) determine interactions between
      phytochemicals of interest in Saint John's Wort (SJW) with several excipients;
      and (3) explore the application of similarity metrics to the data. Modifications
      to conventional isothermal stress testing paradigms included additional storage
      conditions of heat and moisture (5, 50 degrees C, 5 and 0% added water), as well
      as more rigorous controls. Binary blends of SJW and ten commonly used excipients
      were prepared and neat SJW was used as control. After 3 weeks, the percentage
      remaining of each phytochemical was determined by HPLC. Several similarity
      metrics were applied to the data. Common storage paradigms were suitable for
      excipient compatibility testing when controls of neat material are stored under
      similar conditions and the percentage of phytochemicals remaining in
      excipient:SJW blends and neat SJW are compared. Excipient incompatibilities were
      determined for SJW phytochemicals of interest. Similarity metrics applied to the
      phytochemical profiles conveniently summarized the data. This work allows logical
      decisions to be made regarding the formulation of SJW.

PMID- 11955803
TI  - Studies on mechanism of 8-methoxypsoralen-DNA interaction in the dark.
AB  - The interaction of 8-methoxypsoralen (8-MOP) with calf thymus DNA was studied in
      darkness at 25 degrees C and pH 7.4. The enthalpy curve for 8-MOP-DNA interaction
      was obtained by isothermal titration calorimetry and showed a two-step process
      for the interaction. According to the spectrophotometric data, it was suggested
      that some compaction may occur in the DNA structure at higher [8-MOP](t)/[DNA]
      ratio. Using the fluorescence quenching data, the Scatchard analysis was
      performed for 8-MOP-DNA interaction at the extended ranges of drug concentration.
      The results indicated that the first set of binding sites was occupied by 1 mol
      of drug bound per near eight base pairs of DNA. Also 8-MOP caused the quenching
      of the fluorescence emission of DNA-ethidium bromide complex. The Scatchard
      analysis of these data indicated the non-competitive manner for quenching. A non
      displacement based quenching mechanism has been suggested for this behavior. The
      circular dichroism spectra also confirmed the non-intercalative binding of 8-MOP
      at higher concentrations accompanied by some conformational changes in DNA
      structure. It has been suggested that at low drug load, 8-MOP binds to DNA as an
      intercalator, which is an endothermic process, whereas at higher ratios of [8
      MOP](t)/[DNA], it binds to the outside of DNA, probably in the minor groove and
      causes some compaction in DNA, which is the exothermic process.

PMID- 11955804
TI  - Protection mechanism of Tween 80 during freeze-thawing of a model protein, LDH.
AB  - The purpose of the study was to investigate the protective mechanism of a non
      ionic surfactant, Tween 80, at freeze-thawing with controlled temperature history
      of a model protein, lactate dehydrogenase (LDH). The system was examined by
      differential scanning calorimetry (DSC) and infrared spectroscopy (IR). LDH
      activity assays were performed spectrophotometrically. In all samples,
      independent of temperature history and addition of surfactant, all water was
      crystallized to polycrystalline ice at temperatures below -20 degrees C. The size
      and perfection of the ice crystals could be varied by a range of cooling rates
      giving different degrees of undercooling. At Tween concentrations below the cmc
      at crystallization, lower concentrations were required at low cooling rates
      compared to higher cooling rates to protect LDH. Concentrations above cmc of
      Tween reduced the protection at a cooling rate of 5 degrees C min(-1) and at
      quenching in N(2)(l). The amount of Tween needed for complete protection
      correlated to the surface area of the ice crystals at a certain temperature
      history. Tween 80 protects LDH from denaturation at freeze-thawing by hindering
      its destructive interaction with the ice crystals. The protective effect might be
      obtained when Tween molecules compete with the protein for sites on the ice
      surface. The optimum concentration of Tween needed for complete protection is
      dependent on the temperature history.

PMID- 11955805
TI  - Oral delivery of insulin from enteric-coated capsules containing sodium
      salicylate: effect on relative hypoglycemia of diabetic beagle dogs.
AB  - The hypoglycemic effect of Eudragit S100 enteric-coated capsules containing
      sodium salicylate as an absorption promoter formulated with insulin in various
      ways: as physical mixture, by wet granulation or in suppository bases
      (polyethylene glycol 4000 or Witepsol W35) was studied in hyperglycemic beagle
      dogs. The capsules containing insulin formulated with sodium salicylate (50 mg)
      and prepared by either physical mixing or wet granulation using 10% polyvinyl
      pyrollidone gave almost the same results producing a maximum reduction in plasma
      glucose level (C(max)) of 81.53+/-8.21 and 79.59+/-5.75%, T(max) of 6 and 5 h,
      area under the curve (AUC) of 69.37+/-48.64 and 57.98+/-23.15% reduction hour (%
      red. h) and resulting in relative hypoglycemia (RH) of 8.73+/-6.12 and 7.29+/
      2.91%, respectively. Formulation of insulin with sodium salicylate in PEG 4000
      produced a lower AUC of 37.30+/-10.36% red. h and RH of 4.69+/-1.3%. While,
      formulation in Witepsol W35 (0.5, 1.0 and 2.0 g) that was sieved to produce
      particle size of 180-315 microm and filled in enteric-coated capsules showed that
      formulating insulin and sodium salicylate in 1 g base is the best formulation. It
      produced 25% reduction in plasma glucose levels of the hyperglycemic beagle dogs
      at T(max) of 4 h and the largest AUC of 100.10+/-25.72% red. h, resulting in the
      highest RH of 12.59+/-3.23%. In conclusion, 25-30% reduction in plasma glucose
      levels and RH of about 12.5% relative to subcutaneous injection of regular
      soluble insulin can be achieved by formulating insulin in Witepsol W35 (1 g) with
      sodium salicylate (50 mg) as an absorption promoter, reducing the resulting mass
      into particle size 180-315 microm, packing into hard gelatin capsules and coating
      with Eudragit S100.

PMID- 11955806
TI  - Development of an ethyl laurate-based microemulsion for rapid-onset intranasal
      delivery of diazepam.
AB  - An ethyl laurate-based microemulsion system with Tween 80 as surfactant,
      propylene glycol and ethanol as cosolvents was developed for intranasal delivery
      of diazepam. Phase behavior and solubilization capacity of the microemulsion
      system were characterized and in vivo nasal absorption of diazepam from
      microemulsion formulations was investigated in rabbits. A single isotropic
      region, which is considered as a bicontinuous microemulsion, was found in the
      pseudo-ternary phase diagrams developed at various Tween 80: propylene glycol:
      ethanol ratios. With the increase of Tween 80 concentration, the microemulsion
      region area, microemulsion viscosity, and the amount of H(2)O and ethyl laurate
      solubilized into the microemulsion system increased; however, the increase of
      ethanol percentage produced opposite effects. Diazepam, a practically water
      insoluble drug, displayed a high solubility of 41 mg/ml in a microemulsion
      consisting of 15% ethyl laurate, 15% H(2)O, and 70% (w/w) surfactant/cosurfactant
      (Tween 80:propylene glycol:ethanol at 1:1:1 weight ratio). Nasal absorption of
      diazepam from this microemulsion was found to be fairly rapid. At 2 mg/kg dose,
      the maximum drug plasma concentration was arrived within 2-3 min, and the
      bioavailability (0-2 h) after nasal spray compared with intravenous injection was
      about 50%. These results suggest that this ethyl laurate-based microemulsion may
      be a useful approach for the rapid-onset delivery of diazepam during the
      emergency treatment of status epilepticus.

PMID- 11955807
TI  - Identification of critical process variables for coating actives onto tablets via
      statistically designed experiments.
AB  - The objective of this work was to identify, using a statistical experimental
      design, the critical processing variables that affect content uniformity and
      loading of active agent coated on tablets in a 24" Accela-Cota. United States
      Pharmacopeia (USP) specifies that the % relative standard deviation (RSD) of drug
      content within a batch should be less than 6%. A Plackett-Burman experimental
      design was used to identify the process variables that influence the content
      uniformity and loading efficiency of the drug in the aqueous-based film coat of
      the tablets. The process variables investigated were inlet airflow, pan speed,
      inlet air temperature, coating time, atomization pressure, and fan pressure.
      Atomization pressure was identified as a major variable with respect to content
      uniformity (P<0.01). Pan speed and coating duration were also identified as
      variables significantly affecting content uniformity (P<0.05). Fan pressure was
      identified as a critical variable affecting recovery (P<<0.01). Temperature also
      significantly affected recovery (P<0.05). A good correlation was obtained between
      observed and predicted values for content uniformity (r(2)=0.85) and recovery
      (r(2)=0.95). It was possible to achieve % RSD less than 6% while maintaining the
      recovery at 80% or higher.

PMID- 11955808
TI  - Prediction of Caco-2 cell permeability using a combination of MO-calculation and
      neural network.
AB  - In the present study, we developed an approach involving a combination of
      molecular orbital (MO) calculation and neural network to predict Caco-2 cell
      permeability (logP(app)) from the molecular structure of compounds. For a total
      of 87 compounds with logP(app) values obtained from the literature, three
      dimensional molecular structures were determined by MO-calculation, and then five
      molecular descriptors were obtained, namely, the dipole moment, polarizability,
      sum of charges of nitrogen atoms (sum(N)), oxygen atoms (sum(O)), and hydrogen
      atoms bonding to nitrogen or oxygen atoms (sum(H)). The correlation between these
      five molecular descriptors and logP(app) was analyzed using a feed-forward back
      propagation neural network with a configuration of 5-4-1 for input, hidden, and
      output layers found suitable for predicting Caco-2 cell permeability. A leave-one
      out cross-validation procedure revealed that the neural network model possesses a
      fairly good predictability as far as Caco-2 cell permeability is concerned
      (predictive root mean square error (RMSE)=0.507), and better than the simple and
      quadratic regression model (predictive RMSE=0.584 and 0.568, respectively).

PMID- 11955809
TI  - Didanosine extended-release matrix tablets: optimization of formulation variables
      using statistical experimental design.
AB  - Statistical experimental design was applied to evaluate the influence of some
      process and formulation variables and possible interactions among such variables,
      on didanosine release from directly-compressed matrix tablets based on blends of
      two insoluble polymers, Eudragit RS-PM and Ethocel 100, with the final goal of
      drug release behavior optimization. The considered responses were the percent of
      drug released at three determined times, the dissolution efficiency at 6 h and
      the time to dissolve 10% of drug. Four independent variables were considered:
      tablet compression force, ratio between the polymers and their particle size, and
      drug content. The preliminary screening step, carried out by means of a 12-run
      asymmetric screening matrix according to a D-optimal design strategy, allowed
      evaluation of the effects of different levels of each variable. The drug content
      and the polymers ratio had the most important effect on drug release, which,
      moreover, was favored by greater polymers particle size; on the contrary the
      compression force did not have a significant effect. The Doehlert design was then
      applied for a response-surface study, in order to study in depth the effects of
      the most important variables. The desirability function was used to
      simultaneously optimize the five considered responses, each having a different
      target. This procedure allowed selection, in the studied experimental domain, of
      the best formulation conditions to optimize drug release rate. The experimental
      values obtained from the optimized formulation highly agreed with the predicted
      values. The results demonstrated the reliability of the model in the preparation
      of extended-release matrix tablets with predictable drug release profiles.

PMID- 11955810
TI  - Lipase degradation of Dynasan 114 and 116 solid lipid nanoparticles (SLN)--effect
      of surfactants, storage time and crystallinity.
AB  - In vivo drug release from solid lipid nanoparticles (SLN) takes place by
      diffusion and degradation of the lipid matrix. SLN with different degree of
      crystallinity were prepared to study the effect of crystallinity on the
      degradation velocity. These SLN were produced by using glycerides with different
      length of fatty acid chains and known differences in crystallisation velocity
      (Dynasan 114 and 116), and using stabilisers interfering differently with the
      crystallisation process of the lipid matrix (cholic acid sodium salt (NaCh),
      Poloxamer 407 (Plx 407)). NaCh disturbs the crystallisation process, Poloxamer
      shows little interference. The particles were characterised by photon correlation
      spectroscopy (PCS) and differential scanning calorimetry (DSC), degradation
      velocity was determined directly after production and during storage up to 4
      weeks under different storage conditions using an especially developed assay
      based on the NEFA Test kit. After production, SLN with a lower crystallinity
      matrix (Dynasan 114 and 116, NaCh) degraded faster than higher crystalline
      particles (all SLN with Plx 407), and showed a decrease in degradation velocity
      with increasing crystallinity during storage. Fast crystallising particles made
      from Dynasan 116 stabilised with the non-interfering Plx 407 showed no change in
      the degradation velocity during storage. SLN produced with a higher crystalline
      lipid in combination with the crystallisation-disturbing NaCh (Dynasan 116, NaCh)
      required a 'ripening time' to reach sufficient crystallinity.

PMID- 11955811
TI  - Targetability and intracellular delivery of anti-BCG antibody-modified, pH
      sensitive fusogenic immunoliposomes to tumor cells.
AB  - We prepared tumor-specific immunoliposomes by coupling anti-BCG monoclonal
      antibodies to pH-sensitive fusogenic liposomes modified with succinylated
      polyglycidol (sucPG), in order to obtain efficient binding to, and endocytotic
      internalization into, the tumor cells. Mouse colon carcinoma 26 cells, which are
      known to share a common antigen with BCG, were used in in vitro experiments. BCG
      sucPG immunoliposomes showed fusion ability under acidic conditions. Fluorescence
      microscopic observation indicated that BCG-sucPG immunoliposomes bound to colon
      26 tumor cells and induced receptor-mediated endocytosis at 37 degrees C. Fusion
      assay by resonance energy transfer using N-(7-nitro-2-1,3-benzoxadiazol-4-yl)
      diacyl phosphatidylethanolamine and N-(lissamine rhodamine B sulfonyl) diacyl
      phosphatidylethanolamine suggested that fusion between BCG-sucPG immunoliposomes
      and endosomal and/or lysozomal membrane did occur. These results imply that the
      BCG-sucPG immunoliposomes transfer their content into the cytoplasm by fusing
      with the endosomal and/or lysozomal membrane after recognition of target cells
      and subsequent internalization into the cells by endocytosis.

PMID- 11955812
TI  - Comparison of the mechanical destructive force in the small intestine of dog and
      human.
AB  - The purpose of this study was to evaluate the destructive force that oral solid
      dosage forms receive in the small intestine of dogs and humans. Information on
      the mechanical destructive forces of the gastrointestinal tract (GI) helps
      formulation design research in the following way: (1) to improve the
      predictability of the dissolution test since in vivo drug release is affected by
      not only agitation intensity but also mechanical stress; (2) to design safe and
      robust products by avoiding dose-dumping or unintended drug release at an
      inadequate site; (3) to better understand the species difference in
      bioavailability by comparing the destructive forces against dosage forms in the
      GI of dogs with those of humans. "Destructive force Dependent Release System"
      (DDRS) was developed to measure the mechanical destructive forces of the GI tract
      by using highly hydrophobic Teflon powder. In a DDRS, a marker drug contained in
      the core tablet is released only when the DDRS receives a force larger than its
      pre-determined crushing strength. DDRS-Small Intestine (DDRS-SI), a modified
      DDRS, was prepared for targeting the small intestine. DDRS-SI was encapsulated in
      starch capsules (Capill) and then the capsules were coated with an enteric film
      (DDRS-SI-Ecap). The capsules were administered to six dogs and nine human
      volunteers. Both dogs and human volunteers crushed a DDRS-SI having a crushing
      strength of 1.2 N. Therefore, these controlled-release formulations should
      withstand a destructive force of 1.2 N when they pass through the small
      intestine.

PMID- 11955813
TI  - Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term
      stability.
AB  - The poorly soluble drug buparvaquone is used in experimental clinics against the
      gastrointestinal persisting parasite Cryptosporidium parvum. It was produced as
      nanosuspension by high pressure homogenisation. Main advantages of
      nanosuspensions (amongst others) are their increase of saturation solubility and
      dissolution velocity, improving the bioavailability of drugs. The buparvaquone
      nanosuspension had a bulk population of about 600 nm (analysed by photon
      correlation spectroscopy (PCS)). The additional analysis performed with laser
      diffraction showed that only a very small content of microparticles occurred,
      which is, for the special features of nanosuspensions, negligible because they
      were still below 3 microm. Another feature of nanosuspensions is the adhesion
      properties to surfaces, e.g. mucosa. To further increase the adhesion time of the
      buparvaquone nanosuspension to C. parvum, the nanosuspension was formulated with
      hydrogels made from mucoadhesive polymers, e.g. different types of Carbopol and
      chitosan. Only a small increase of the particle size of the bulk population
      occurred directly after the incorporation of buparvaquone nanosuspension into the
      hydrogels. The nanosuspension/hydrogel systems were physically long-term stable
      over a period of 6 months as indicated by the unchanged particle sizes.

PMID- 11955814
TI  - Effects of polyethylene glycol attachment on physicochemical and biological
      stability of E. coli L-asparaginase.
AB  - L-asparaginase obtained from E. coli strains is an important enzyme widely used
      in leukemia treatment. However, hypersensitivity reactions must be considered a
      relevant adverse effect of asparaginase therapy. One approach to reduce the
      hypersensitivity reactions caused by this enzyme is to change its physicochemical
      and biological properties by means of polyethylene glycol (PEG) conjugation,
      resulting in a less immunogenic enzyme with much longer half-time of plasmatic
      life. This work investigated the factors that could interfere in PEG-enzyme's
      stability. The complexation did not affect the range of pH activity and stability
      was improved in acid medium remaining stable during 1 h at pH 3.5. The PEG-enzyme
      exhibited activity restoration capacity (32% after 60 min) when subjected to
      temperatures of 65 degrees C in physiological solution. The PEG-enzyme in vitro
      assays showed a very high stability in a human serum sample, keeping its activity
      practically unchanged during 40 min (strength to non-specific antibodies or
      proteases in serum). An increase of PEG-enzyme catalytic activity during the
      lyophilization was observed. The process of modification of L-asparaginase with
      PEG improved both physicochemical and biological stability.

PMID- 11955815
TI  - A study of the crystallisation of amorphous salbutamol sulphate using water
      vapour sorption and near infrared spectroscopy.
AB  - The crystallisation of amorphous salbutamol sulphate prepared by spray drying was
      monitored using a humidity controlled microbalance (Dynamic Vapour Sorption
      apparatus, Surface Measurement Systems) combined with a near-infrared probe.
      Amorphous salbutamol sulphate was prepared by spray drying from a solution in
      water. The particles were then analysed using scanning electron microscopy,
      thermogravimetric analysis, differential scanning calorimetry, powder X-ray
      diffraction, isothermal microcalorimetry and water vapour sorption analysis
      combined with near-infrared spectroscopy (NIR). Isothermal microcalorimetry and
      water vapour sorption combined with NIR spectroscopy were able to detect the
      transition from the amorphous to crystalline state. However while the isothermal
      microcalorimeter showed only a classic crystallisation exotherm when the material
      was exposed at 75% RH, the DVS-NIR results at the same humidity highlighted a
      more complex process. When exposed at 75% RH, the uptake of water was followed by
      crystallisation that was detected using NIR. The expulsion of water after
      crystallisation was very slow and at a constant rate whether the material was
      exposed to 75 or 0% RH. The NIR and DVS studies indicated that the material had
      crystallised very soon after exposure to high RH. The water that was expelled
      during crystallisation was not displaced from the particles and remained
      associated with the particles for many days. This study showed that the use of
      gravimetric analysis together with NIR spectroscopy provided valuable information
      on the dynamics of the crystallisation of salbutamol sulphate. The retention of
      water within recently crystallised salbutamol is potentially important to the
      behaviour of dosage forms containing the amorphous (or partially amorphous) form
      of this drug.

PMID- 11955816
TI  - Nasal absorption enhancement strategies for therapeutic peptides: an in vitro
      study using cultured human nasal epithelium.
AB  - This study examined the potential usefulness of cultured human nasal epithelium
      as a model to investigate nasal absorption enhancement strategies for therapeutic
      peptides. The transport of leucine enkephalin (Leu-Enk) in the presence of
      bestatin and puromycin, respectively and various combinations of these protease
      inhibitors with absorption enhancers capable of inhibiting proteases or
      protecting peptides against protease degradation (glycocholate, dimethyl-beta
      cyclodextrin (DM beta CD)) was studied. Epithelial membrane perturbation, protein
      leakage, bestatin/puromycin absorption and rebound aminopeptidase activity were
      used as toxicological end-points. The combination of puromycin with glycocholate
      or DM beta CD resulted in a higher absorption enhancement of Leu-Enk (9-14%) than
      when the absorption enhancers were combined with bestatin (1-3%) or when the
      inhibitors were used alone (2-4%). The higher absorption enhancement resulting
      from the combination of protease inhibitors with absorption enhancers caused a
      significant reduction of epithelial resistance and increased sodium fluorescein
      transport. Although only puromycin permeated the human nasal epithelium, both
      protease inhibitors induced a significant rebound aminopeptidase activity (25
      61%), which can be associated with protein leakage (21-46%). This study
      highlighted (i) the potential usefulness of cultured human nasal epithelium as a
      model to study nasal absorption enhancement of therapeutic peptides; (ii) further
      studies using in vivo nasal models are required to ascertain whether the membrane
      perturbation and cytotoxicity observed with various combinations of the protease
      inhibitors and absorption enhancers really raise safety concerns.

PMID- 11955817
TI  - Correlation of aqueous solubility of salts of benzylamine with experimentally and
      theoretically derived parameters. A multivariate data analysis approach.
AB  - Twenty two salts of benzylamine and p-substituted benzoic acids were prepared and
      characterized. The p-substituent was varied with regard to electronic,
      hydrophobic, and steric effects as well as hydrogen bonding potential. A
      multivariate data analysis was used to describe the relationship between the
      aqueous solubility of the salts and experimentally determined physicochemical
      parameters and theoretically derived molecular descriptors. The model, based on
      all descriptors, gave R(2)=0.86 and Q(2)=0.72. The most significant descriptors
      exhibiting VIP (variance of importance) values above 1.0 were intrinsic
      dissolution rate, intrinsic solubility of the unionized acids (S(0)), Hansch's
      hydrophobic parameter, Charton's steric parameter and molecular weight (MW).
      Statistically good models for predicting solubility of a selected test set were
      obtained by using simple models consisting of a few descriptors only: (i)
      Charton, Hansch and MW (R(2)=0.73; Q(2)=0.70), and (ii) Charton and S(0)
      (R(2)=0.74; Q(2)=0.72).

PMID- 11955818
TI  - Effect of different terpene-containing essential oils on permeation of estradiol
      through hairless mouse skin.
AB  - Purpose of the present investigation was to evaluate six terpene-containing
      essential oils for their capacity to promote permeation of estradiol (ES) through
      hairless mouse skin in vitro. Tests on cajuput, cardamom, melissa, myrtle,
      niaouli and orange oil, all used at the 10% w/w concentration in propylene glycol
      (PG), evidenced niaouli oil (NIA) as the best permeation promoter for ES. Tests
      on the main terpene components of NIA (1,8 cineole, alpha-pinene, alpha-terpineol
      and D-limonene), evaluated neat (10% w/w in PG) or in admixture, confirmed the
      better promoting activity of whole NIA. The present data point to the validity of
      complex terpene mixtures, such as that composing NIA, as transdermal penetration
      enhancers for moderately lipophilic drugs like ES.

PMID- 11955820
TI  - Lectin-mediated drug delivery: binding and uptake of BSA-WGA conjugates using the
      Caco-2 model.
AB  - To examine whether the dietary lectin wheat germ agglutinin (WGA) can facilitate
      binding and uptake of protein drugs due to its cytoadhesive and cytoinvasive
      properties, conjugates were prepared by covalent coupling of fluorescein-labeled
      bovine serum albumin (F-BSA) to WGA using divinylsulfone for crosslinking.
      Increasing the molar ratio of F-BSA/WGA resulted in 2.6-8.7 times higher Caco-2
      binding as compared with glycyl-F-BSA. About 75% of F-BSA-WGA were bound
      specifically to Caco-2 cells according to inhibition studies in presence of the
      complementary carbohydrate. The Caco-2 association of F-BSA-WGA was temperature
      dependent indicating active uptake of membrane bound conjugate, which was
      confirmed by confocal microscopy. The conjugate accumulated within lysosomal
      compartments followed by proteolytic degradation of F-BSA-WGA 1-4 h after
      conjugate loading as observed by equilibrating the intracellular pH with
      monensin. Finally low molecular weight degradation products of the proteinaceous
      prodrug appear in the extracellular medium. Contrary to Caco-2 single cells, a
      minor part of the conjugate is degraded by brush border proteases already 30 min
      after exposure to Caco-2 monolayers. But most of the conjugate is taken up into
      differentiated cells and processed as in single cells. Though the enzymic barrier
      remains to be surmounted, WGA-mediated drug delivery is a promising strategy for
      peroral delivery of even high molecular weight drugs to overcome the mucosal
      barrier.

PMID- 11955819
TI  - Development and evaluation of a biphasic buccal adhesive tablet for nicotine
      replacement therapy.
AB  - Bilayer nicotine mucoadhesive tablets were prepared and evaluated to determine
      the suitability of the formulation as a nicotine replacement product to aid in
      smoking cessation. A range of formulations containing 0-50% w/w Carbopol 934 and
      0-50% w/w hydroxypropylcellulose (HPC) were prepared and tested for adhesive
      properties and drug release. Mucoadhesion was assessed using bovine buccal
      mucosa. Peak detachment force of the tablets was found to reach a maximum at 20%
      w/w Carbopol 934, whilst work of adhesion continued to increase with Carbopol 934
      concentration. HPC concentrations of 20-30% w/w were found to provide nicotine
      hydrogen tartrate (NHT) release approaching zero order kinetics over a 4 h test
      period. A combination of 20% w/w Carbopol 934 and 20% w/w HPC was thus found to
      provide suitable adhesion and controlled drug release. The formulation of a
      bilayer tablet containing the adhesive controlled release layer (CRL) and a fast
      releasing layer provided an initial burst release of NHT followed by the
      controlled release for a period of up to 4 h. The same biphasic type of release
      was identified during an in vivo assessment using human volunteers This biphasic
      drug release could represent an improvement over current methods of nicotine
      replacement.

PMID- 11955821
TI  - Determination of the required HLB values of some essential oils.
AB  - The required HLB values of eucalyptus, lippia and peppermint essential oils were
      determined using droplet size analysis and turbidimetric method on emulsions
      prepared with emulsifier blends of varying HLB values. The percentage increase in
      mean droplet diameter and the degree of dispersion of droplet sizes were
      determined before and after centrifugation of the emulsions. The HLB value of the
      emulsion with the least dispersion ratio or the least percentage increase in mean
      droplet diameter was taken as the required HLB of the respective essential oil.
      The turbidimetric method was validated by the existence of correlation (r=-0.958)
      between the mean droplet diameter and the turbidity of the emulsions. The
      turbidity curve went through a maximum at the HLB value where the mean droplet
      diameter was least. Based on these methods, the required HLB values of
      eucalyptus, lippia and peppermint oils were determined as 9.8, 12.1 and 12.3,
      respectively (P<0.05). Liquid paraffin was used as a reference standard and its
      required HLB fell within literature value.

PMID- 11955823
TI  - Citalopram in fatal poisoning cases.
AB  - Citalopram, a selective serotonin reuptake inhibitor, is the most frequently
      prescribed antidepressant in Sweden. To investigate the extent to which
      citalopram in overdose is found in fatal poisoning cases compared with other
      drugs, all fatal poisonings in one forensic medicine district in Sweden during
      the years 1994-1999 were examined. Drugs found in overdose in more than 10 cases
      were included. The ratio between number of cases with each included drug and
      prescription of defined daily dose/1,000 inhabitants/day (DDD) was determined.
      Citalopram was the fourth most frequently found drug in overdose, occurring in 22
      (6%) of the 358 fatal poisoning cases, after dextropropoxyphene (DXP),
      flunitrazepam and nitrazepam, which were present in 111 (31%), 56 (16%) and 31
      (9%) cases, respectively. When related to the prescription rate, citalopram was
      significantly less represented than five of the other seven included drugs,
      namely DXP, flunitrazepam, nitrazepam, amitriptyline and clomipramine.
      Propiomazine and zopiclone occurred to the same extent as citalopram. According
      to the assessments of the forensic physicians, citalopram was the cause of death
      in five cases (1.4%) and contributed to death in another nine cases (2.5%). It is
      concluded that citalopram, in spite of its high prescription rate, has not become
      a drug of importance in fatal poisoning cases. Since, this result may not be
      generalisable to non-fatal poisoning cases, it is recommended that the prevalence
      of citalopram in these cases be examined separately.

PMID- 11955824
TI  - The cocaine "body stuffer" syndrome: a fatal case.
AB  - Body stuffer, sometimes called "mini packer", is the definition of someone who
      admits to or is strongly suspected of ingesting illegal drugs in order to escape
      detection by authorities, and not for recreational purposes or to transport the
      drug across borders. Cocaine is the drug most commonly involved in the body
      stuffer syndrome. Reported cases of body stuffer deaths are rare, however a
      fatality related to the ingestion of a plastic bag containing cocaine is
      described regarding a 17-year-old dealer. The authors describe how the cocaine
      body stuffer syndrome differs from the usual body packer. Histological and
      toxicological findings are examined and discussed for a better definition of this
      unique syndrome.

PMID- 11955825
TI  - The origin of evidence.
AB  - Forensic science is an applied science based on the laws of physics and
      chemistry. Over time, a set of fundamental concepts has developed that apply
      specifically to a forensic analysis. Traditionally, five concepts have been
      articulated: transfer, identification, individualization, association between
      source and target, and reconstruction. We suggest that an additional sixth
      concept, the idea that matter must divide before it can be transferred, is
      necessary to complete the paradigm. Divisible matter is particularly useful in
      describing physical match evidence. Additionally, we propose a paradigm that
      logically divides into scientific principles that govern the generation of
      evidence, and processes that pertain to the recognition, analysis, and
      interpretation of evidence. The principles of divisible matter and transfer
      pertain to the generation of evidence before and during the crime event; the
      processes of identification, classification or individualization, association,
      and reconstruction describe the practice of forensic science starting with the
      recognition of an item as evidence.

PMID- 11955826
TI  - Partition coefficient, blood to plasma ratio, protein binding and short-term
      stability of 11-nor-Delta(9)-carboxy tetrahydrocannabinol glucuronide.
AB  - 11-Nor-Delta(9)-carboxy tetrahydrocannabinol glucuronide (THCCOOglu) is a major
      metabolite of tetrahydrocannabinol in blood. Despite its mass spectrometric
      identification already in 1980, further physicochemical data of THCCOOglu have
      not been established. Therefore, the octanol/buffer partition coefficient P and
      the blood to plasma ratio b/p for THCCOOglu concentrations of 100 and 500ng/ml
      were investigated. Protein binding of the glucuronide was established from spiked
      albumin solutions at a level of 250ng/ml as well as from authentic samples. The
      data were compared to those of 11-nor-Delta(9)-carboxy tetrahydrocannabinol
      (THCCOOH). In addition, the short-term stability of THCCOOglu in plasma at
      different storage temperatures was studied. Analysis was performed by LC/MS/MS.
      The glucuronide partition coefficient P (mean: 17.4 and 18.0 for 100 and
      500ng/ml, respectively) was unexpectedly lipophilic at pH 7.4. Its blood to
      plasma ratios averaged 0.62 and 0.68 at 100 and 500ng/ml, respectively. THCCOOglu
      was highly reversibly bound to albumin (mean: 97%), and the mean fraction bound
      did not differ from that determined from authentic samples. THCCOOglu degraded
      even at a storage temperature of 4 degrees C and THCCOOH was identified as a
      major decomposition product.

PMID- 11955827
TI  - A kinetic model describing the pharmacokinetics of ethyl glucuronide in humans.
AB  - The glucuronide conjugation is a minor pathway of ethanol metabolism. The
      determination of ethyl glucuronide (EG) in serum and urine has gained importance
      in forensic and other legal decisions. To prospectively calculate the serum
      concentration of this non-oxidative ethanol metabolite, the computer program
      developed includes a parameter fitting routine. Multiple ethanol doses can be
      handled. The mathematical modeling was based on the following assumptions and
      simplifications, respectively. A single enzyme system is responsible for ethanol
      conjugation at one distinct site; the distribution of EG into the systemic
      circulation is delayed; the elimination of EG follows first-order kinetics. The
      concentration of EG was calculated using three kinetic parameters: a rate
      constant for the first-order formation of EG from serum ethanol, a transfer
      constant for an obstructed transfer of EG from the formation site (FS) into the
      central compartment (CC) and an exponential elimination constant. The program was
      applied to the data collected from 21 drinking experiments. The fitting algorithm
      optimized the three kinetic parameters, until the sum of concentration error
      squares of the data points was minimized. The means+/-standard deviation of the
      rate constant for the first-order formation of EG from serum ethanol was 0.0011+/
      0.0006 h(-1), the transfer constant for an obstructed transfer of EG from the FS
      into the CC was 0.43+/-0.1996 h(-1) and the exponential elimination constant was
      3.0+/-1.45 h(-1). Using the range of these parameters, it is now possible to
      calculate minimum and maximum serum concentrations of EG based on ethanol doses
      and drinking times. The comparison of calculated and measured concentrations can
      prove the plausibility of an alleged ethanol consumption. This can be crucial
      when the serum ethanol concentration (SEC) itself is not meaningful.

PMID- 11955828
TI  - Critique of interpretation of high levels of heteroplasmy in the human
      mitochondrial DNA hypervariable region I from hair.
AB  - The phenomenon known as heteroplasmy can be operationally observed in some human
      mitochondrial DNA (mtDNA) samples. Typically, heteroplasmy manifests itself in an
      individual presenting two mtDNA species that differ at a single base.
      Heteroplasmy at two, and even possibly three sites, also may occur, but at very
      low rates. A recent report (Grzybowski, 2000, see ref. [13]) suggests that much
      higher levels of mtDNA (point substitution) heteroplasmy can occur in hair. This
      observation is contrary to the experience of the forensic mtDNA community. There
      are several explanations for the unusual findings of high levels of heteroplasmy.
      First, the template quantities of DNA are approximately three orders of magnitude
      higher than required for mtDNA sequencing, and an excessive number of
      amplification cycles were used. Thus, the protocol used did not follow routine
      practices by the forensic community. Second, there are misidentifications and
      tabular errors that call into question the reliability of the findings. Third, by
      comparing the natural human mtDNA variation with a reference sample population
      with that observed in the heteroplasmy in hair study, the data are inconsistent
      with population genetic expectations. The observation of high levels of
      heteroplasmy may be due to contamination of the samples and/or possibly the
      amplification of nuclear pseudogenes. The results observed in the heteroplasmy in
      hair study do not apply to other methods of mtDNA analysis and cannot be used to
      question the reliability of the current forensic mtDNA practices.

PMID- 11955829
TI  - Quantification of human mitochondrial DNA in a real time PCR.
AB  - Recently, a moderately priced machine for real-time quantitative PCR has become
      available, the Perkin Elmer 5700. The rapid and quantitative assay of
      mitochondrial DNA (mtDNA) copy number is potentially useful in a variety of
      molecular, evolutionary and forensic fields. Using this new tool, we have
      evaluated the precision and reliability of the real time PCR to quantify
      undeleted mitochondrial genome copy number, and to determine the frequency of an
      age-associated deletion of 4977 base pairs in length, in 42 human iliopsoas
      muscle DNA samples from persons of known age. We have evaluated the accuracy with
      which age can be predicted, knowing only the frequency of this common 4977 bp
      deletion, and derived a statistical formula which describes the confidence with
      which the 4977 bp frequency predicts age. The results indicate that the mutation
      frequency could be used to distinguish between tissue from young and old
      individuals. However in this data set, while there was considerable agreement of
      4977 bp frequency among replicates from the same individual sample, there was
      substantial diversity of mean mutation frequency between individuals of the same
      or similar ages. The simplest interpretation of these results is that there are
      biological modifiers of 4977 bp frequency that are age-independent, which are
      potentially interesting but may limit the usefulness of this deletion frequency
      alone as a "molecular forensic clock."

PMID- 11955831
TI  - Analysis of postmortem DNA degradation by single-cell gel electrophoresis.
AB  - One of the most important longstanding problems in the field of forensic medicine
      is the determination of the time of death upon the discovery of a possible
      homicide victim. With a majority of homicide victims discovered within the first
      48h, it is critically important to be able to determine time of death quickly,
      and with accuracy and precision. Current methods of determining postmortem
      interval (PMI) vary, but none can provide better than an 8-h window time
      estimate. In this paper, the potential application of single-cell gel
      electrophoresis (SCGE), also known as the comet assay, to evaluate postmortem
      cell death processes, specifically nuclear DNA fragmentation, is assessed. Upon
      the death of an organism, internal nucleases contained within the cells should
      cause chromosomal DNA to degrade into increasingly smaller fragments over time,
      and if these fragments can be isolated and visualized, the fragmentation should
      prove to be measurable and quantifiable. An original study providing proof of the
      concept of postmortem DNA fragmentation between early and late time periods was
      conducted using human leukocytes. With an established trend seen in the leukocyte
      results, this study was then expanded using a porcine animal model, over a longer
      time period, with more frequent time-points evaluated. DNA degradation in all
      samples was revealed by SCGE and quantified by the use of DNA-specific
      quantitative stains, as measured by digital camera affixed to a microscope. The
      comet 'tail-moment' gave a measure of the proportion of fragmented to non
      fragmented DNA, while the 'tail-length' provided the relative size of degraded
      DNA fragments. In both models, an increase in DNA fragmentation was found to
      correlate with an increased PMI from 0 to 56h postmortem, as evaluated by comet
      tail-moment and by comet-tail-length, with tail-length providing the strongest
      statistical correlation, based upon regression analysis. The postmortem DNA
      fragmentation observed in this study, reveals a sequential, time-dependent
      process with the potential for use as a predictor of PMI in homicide cases.

PMID- 11955830
TI  - Longitudinal brainstem laceration associated with complex basilar skull fractures
      due to a fall: an autopsy case.
AB  - This report describes an autopsy case of a rare longitudinal brainstem laceration
      associated with complex basilar skull fractures. The victim was a 40-year-old
      male who died immediately after falling from a roof (9.2m in height) of a factory
      onto a concrete floor. The postmortem examination revealed an incomplete ring
      fracture of the base of the skull with longitudinal fractures of the sphenoid
      (clivus of the dorsum sellae turcicae) and occipital bones, cerebral contusions
      in the frontal and temporal poles, a longitudinal brainstem laceration at the
      posterior median sulcus of the pons accompanied with multiple contusional
      hemorrhages in the brainstem and corpus callosum. Related blunt-force injuries
      were observed in the parieto-occipital region of the head, shoulder and upper
      back involving the fractures of the cervical and thoracic vertebrae, and sternum
      and ribs, indicating a huge impact to the occiput and subsequent impression of
      the vertebral column into the base of the skull due to violent anteroflexion of
      the neck, which caused the complex basilar skull fractures, contusions and
      longitudinal laceration of the brainstem.

PMID- 11955832
TI  - Postmortem revelation of sickle cell disease following fatal episode of acute
      bronchial asthma.
AB  - A 19-year-old black male with previous history of mild bronchial asthma presented
      sudden dyspnea and died in a state of respiratory distress in spite of
      resuscitation attempts. Autopsy showed typical lesions of acute bronchial asthma
      in a context of long-standing asthma associated with a massive and disseminated
      intravascular sickling. Hemoglobin electrophoresis diagnosed heterozygous sickle
      cell disease. This rare case raises the problem of the accuracy of death
      certificate, especially the difficulties to distinguish postmortem lesions as the
      underlying cause of death or the contributory cause of death.

PMID- 11955833
TI  - A fatal case of amniotic fluid embolism with elevation of serum mast cell
      tryptase.
AB  - A case of a 40-year-old female who died of amniotic fluid embolism is presented.
      This case showed typical histological findings of this syndrome. Postmortem serum
      of this case showed an elevated tryptase level (67.2ng/ml, normal levels
      <10ng/ml). Tryptase is a neutral protease of mast cells, and an important
      indicator of mast cell activation and degranulation. Thus, mast cell activation,
      a central feature of anaphylaxis, may have been involved in the pathogenetic
      mechanism of this case.

PMID- 11955835
TI  - Seasonal patterns of arthropods occurring on sheltered and unsheltered pig
      carcasses in Buenos Aires Province (Argentina).
AB  - Differences in the succession of insects and other Arthropoda (invertebrate
      animals with jointed legs), on domestic pig carcasses placed under a roof and
      under the open sky have been studied in Buenos Aires Province, Argentina
      (latitude 34 degrees 45'S) in all the seasons of the year. Faunal associations
      proved different for each treatment in winter: the common bluebottle Calliphora
      vicina was found in both, but on the sheltered carcass Cochliomyia macellaria and
      the rare Phaenicia cluvia were found as well. In the fall, the difference between
      sheltered and unsheltered carcasses was small (six species on the former and five
      species on the latter); in spring and summer, the difference was negligible.

PMID- 11955834
TI  - Alcoholic cardiomyopathy versus chronic myocarditis--immunohistological
      investigations with LCA, CD3, CD68 and tenascin.
AB  - Dilated cardiomyopathy (DCM) is a disorder of unknown aetiology characterized by
      the left ventricular cavity enlargement and wall thinning associated with reduced
      left ventricular wall motion. DCM in chronic alcoholics is supposed to be caused
      by alcohol induced myocardial damage (alcoholic cardiomyopathy). Nevertheless,
      cardiotropic viruses, such as enteroviruses have long been suspected as causative
      agents for at least some forms of DCM. In the present study, 13 cases of DCM in
      chronic alcoholics were investigated with qualification and quantification of
      infiltrating leucocytes using immunohistological antibodies against leucocyte
      common antigen (LCA), T-lymphocytes (CD3) and macrophages (CD68). In addition,
      the expression of tenascin, playing a role in the initiation of fibrotic changes,
      was examined. All antigens were known to be possibly enhanced in cases of chronic
      myocarditis. Using these immunohistological techniques, 2 out of 13 cases had
      evidence for chronic inflammatory myocardial alterations in the sense of
      lymphocytic infiltrates (>2.0 CD3 T-lymphocytes/visual field at 400 x (HPF); >7
      CD3 T-lymphocytes per mm(2)). These cases were diagnosed as having inflammatory
      cardiomyopathy. The other cases without myocardial inflammation were diagnosed as
      idiopathic/alcoholic DCM.

PMID- 11955836
TI  - Last performance with VIAGRA: post-mortem identification of sildenafil and its
      metabolites in biological specimens including hair sample.
AB  - A 43-year-old man was found dead in a hotel room during a sexual relation with a
      colleague.He was treated both for cardiovascular disease and for erectile
      dysfunction with VIAGRA. A pillbox was found in the room with several tablets of
      verapamil (Isoptine), trimetazidine (Vastarel), yohimbine and bromazepam
      (Lexomil). A box of VIAGRA 25mg was found in his raincoat and two tablets were
      missing. His wife declared during the investigation that he was also treated by
      trinitrine. Autopsy revealed severe coronary artery sclerosis as well as signs of
      previous myocardial infarctions. Blood, urine, bile, gastric content and hair and
      representative tissues for histology were collected for toxicological analysis.
      Sildenafil and yohimbine were screened with liquid chromatography/mass
      spectrometry (LC/MS) and trinitrine with headspace injection (HS)/GC/MS.
      Verapamil and trimetazidine were identified and quantified with LC/diode array
      detection (DAD). Sildenafil was identified in blood, urine, bile and gastric
      content at 105, 246, 1206 and 754ng/ml, respectively. Hair concentration was
      177pg/mg. The desmethyl metabolite was quantified in urine at 143ng/ml. Blood
      concentrations of verapamil and trimetazidine were measured at 659 and 2133ng/ml,
      respectively and were above therapeutic ranges. Trinitrine and yohimbine were not
      identified. These results confirm the absorption of sildenafil, verapamil and
      trimetazidine before the death and hair analysis indicates the chronic use of
      sildenafil. To the author's knowledge, this is the first report of a fatal
      sildenafil-verapamil association, probably by hypotension and cardiac
      dysrhythmia.

PMID- 11955837
TI  - An autopsy case of poisoning by massive absorption of cresol a short time before
      death.
AB  - A 65-year-old male patient who was hospitalized with schizophrenia died about 15
      min later after ingestion of a large volume of saponated cresol solution in a
      mental hospital. Fatal levels of free p- and m-cresol in the heart blood were
      detected at 458.8 and 957.3 microg/ml, respectively, which far exceeded the fatal
      levels determined previously. The levels in the heart muscle, liver and spleen
      tissues were also extremely high, and there was 250 ml of cresol-odor-emitting
      fluid in the stomach. The levels of glucuronic-acid-conjugated p- and m-cresols
      in the heart blood were 38.2 and 85.6 microg/ml, respectively. Although the high
      levels of cresols in the heart blood may be due to diffusion from the stomach
      contents, it is surmised that the essential levels of free and conjugated forms
      in blood were at least 99 and 240 microg/ml, respectively, considering the
      results of postmortem examinations and some case reports. It was concluded that
      about 340 microg/ml of the total cresols was absorbed in a very short period
      following oral ingestion of saponated cresol solution in this case.

PMID- 11955838
TI  - Wounds inflicted by survival-knives.
AB  - A homicidal fatality is presented to demonstrate that the pattern of injuries may
      suggest the use of an unusual sharp force, a survival-knife, the characteristics
      of which are in any case well defined. This knife has saw teeth along the back
      that can leave characteristic scrape marks on the skin.

PMID- 11955840
TI  - Implantable left ventricular assist device bridge-to-transplantation: natural
      selection, or is this the natural selection?.

PMID- 11955839
TI  - Left ventricular assist device therapy improves utilization of donor hearts.
AB  - OBJECTIVES: We sought to determine the survival experiences of patients bridged
      to heart transplantation with either intravenous (IV) inotropes or an implantable
      left ventricular assist device (LVAD). BACKGROUND: Because of the operative risks
      of LVAD implantation and the reported lower mortality associated with inotropic
      therapy, bridging to heart transplantation with inotropes is thought to be the
      preferred treatment option. METHODS: Between April 1, 1996, and May 10, 2001, a
      total of 104 patients were bridged to heart transplantation with either IV
      inotropes (n = 38) or an implantable LVAD (n = 66; HeartMate). Survival was
      compared (Kaplan-Meier method) for three periods: survival to transplantation,
      post-transplantation survival and overall survival (i.e., survival from the onset
      of bridging to follow-up). RESULTS: Survival to transplantation was 81 +/- 5% at
      three months for the LVAD group and 64 +/- 11% for the inotrope group (p = NS).
      Post-transplantation survival was 95 +/- 4% at three years for the LVAD group
      (two deaths) and 65 +/- 10% at three years for the inotrope group (nine deaths; p
      = 0.007). Overall survival was 77 +/- 6% at three years for the LVAD group and 44
      +/- 9% at three years for the inotrope group (p = 0.01). CONCLUSIONS: Overall
      survival for patients who were bridged to heart transplantation with an
      implantable LVAD was superior to that of patients who were bridged with
      inotropes. Bridging to transplantation with an implantable LVAD improves
      utilization of donor hearts.

PMID- 11955841
TI  - Cardiac resynchronization in patients with congestive heart failure and chronic
      atrial fibrillation: effect of upgrading to biventricular pacing after chronic
      right ventricular pacing.
AB  - OBJECTIVES: This study assessed the effects of biventricular pacing (BVP) on
      ventricular function, functional status, quality of life and hospitalization in
      patients with congestive heart failure (CHF), prior atrioventricular (AV)
      junction ablation and right ventricular (RV) pacing performed for chronic atrial
      fibrillation (AF). BACKGROUND: Although the benefit of BVP in CHF should
      theoretically extend to the patient with chronic RV pacing and AF, to our
      knowledge, no study has determined the effects of BVP on symptoms and ventricular
      function in these patients. This patient population allows for the evaluation of
      ventricular resynchronization independent of any BVP-induced changes on the AV
      interval. METHODS: Twenty consecutive patients with severe CHF (ejection fraction
      < or = 0.35, New York Heart Association [NYHA] functional class III or IV), prior
      AV junction ablation and RV pacing performed for permanent AF of at least six
      months' duration were studied. Electrocardiograms, echocardiograms, functional
      status evaluations and quality of life surveys were completed before and at three
      to six months after implant. RESULTS: The NYHA functional classification improved
      29% (p < 0.001). The left ventricular (LV) ejection fraction increased 44% (p <
      0.001), the LV diastolic diameter decreased 6.5% (p <0.003) and the end-systolic
      diameter decreased 8.5% (p < 0.01). The number of hospitalizations decreased by
      81% (p < 0.001). The scores on the Minnesota Living with Heart Failure survey
      improved by 33% (p < 0.01). CONCLUSIONS: We conclude that BVP improves the LV
      function and the symptoms of CHF in patients with permanent AF and chronic RV
      pacing. These benefits are comparable to those described for patients in sinus
      rhythm suggesting that BVP acts through ventricular resynchronization rather than
      optimization of the AV delay.

PMID- 11955842
TI  - Prognostic value of mechanical efficiency in ambulatory patients with idiopathic
      dilated cardiomyopathy in sinus rhythm.
AB  - OBJECTIVES: The purpose of this study was to determine, by analyzing the pressure
      volume relationship, the prognostic value of parameters related to myocardial
      energetics for predicting mortality in patients with dilated cardiomyopathy (DCM)
      in sinus rhythm. BACKGROUND: The relationship between the myocardial energetics
      and the prognosis of patients with DCM in sinus rhythm remains unclear. METHODS:
      We followed 114 ambulatory patients with nonischemic DCM in sinus rhythm for a
      mean period of 5.8 +/- 3.9 years. Over 70% of our patients were in New York Heart
      Association functional class I and class II. Pressure-volume data were obtained
      by the conductance method, and myocardial oxygen consumption per beat (VO(2))
      measurements were obtained. RESULTS: The 3-, 5-, and 10-year cumulative survival
      rates were 88.6%, 80.0%, and 73.9%, respectively. Of the 114 patients, 47 were
      selected randomly to assess their myocardial energetics. By univariate analysis,
      the mechanical efficiency (ME, external work/VO(2)), left ventricular (LV)
      ejection fraction and the LV end-diastolic pressure were statistically associated
      with cardiac death. The ME was the strongest predictor of survival in a Cox
      proportional-hazards analysis (p = 0.011). The best cutoff point of ME identified
      by the receiver-operating curve was 11%. This value had a sensitivity of 100%, a
      specificity of 87% and an overall predictive accuracy of 88% to distinguish
      survivors from nonsurvivors. CONCLUSIONS: This study clearly demonstrates that ME
      is a powerful clinical predictor for cardiac death in patients with mild to
      moderate heart failure and with sinus rhythm. Whether these conclusions apply to
      patients with more severe heart failure requires further investigations.

PMID- 11955843
TI  - The effects of dobutamine on cardiac sympathetic activity in patients with
      congestive heart failure.
AB  - OBJECTIVES: The goal of this work was to study the effects of short-term infusion
      of dobutamine on efferent cardiac sympathetic activity. BACKGROUND: Increased
      efferent cardiac sympathetic activity is associated with poor outcomes in the
      setting of congestive heart failure (CHF). Dobutamine is commonly used in the
      therapy of decompensated CHF. Dobutamine, through its effects on excitatory beta
      receptors, may increase cardiac sympathetic activity. METHODS: Seven patients
      with normal left ventricular (LV) function and 13 patients with CHF were studied.
      A radiotracer technique was used to measure cardiac norepinephrine spillover
      (CANESP) before and during an intravenous infusion of dobutamine titrated to
      increase the rate of rise in LV peak positive pressure (+dP/dt) by 40%. RESULTS:
      Systemic arterial pulse pressure increased significantly in response to
      dobutamine in the normal LV function group (74 +/- 3 mm Hg to 85 +/- 3 mm Hg, p =
      0.005) but remained unchanged in the CHF group. Dobutamine caused a significant
      decrease in LV end-diastolic pressure in the CHF group (14 +/- 2 mm Hg to 11 +/-
      2 mm Hg, p = 0.02), an effect not observed in the normal LV group. In the normal
      LV function group, CANESP did not change in response to dobutamine (75 +/- 22
      pmol/min vs. 72 +/- 22 pmol/min, p = NS). In contrast, dobutamine infusion was
      associated with a significant reduction in CANESP in patients with CHF (199 +/-
      43 pmol/min to 128 +/- 30 pmol/min, p < 0.0009). CONCLUSIONS: Dobutamine infusion
      caused a significant sympatholytic response in patients with CHF. This
      sympathetic withdrawal response is probably related to reduction of LV filling
      pressures and/or activation of ventricular mechanoreceptors with dobutamine
      infusion.

PMID- 11955844
TI  - Radial, carotid and aortic distensibility in congestive heart failure: effects of
      high-dose angiotensin-converting enzyme inhibitor or low-dose association with
      angiotensin type 1 receptor blockade.
AB  - objectives; The aim of this study was to determine whether in patients with
      congestive heart failure (CHF) a distensibility (Dist) reduction: 1) similarly
      occurs in different arteries; 2) is related to CHF severity; and 3) is reversible
      with treatment. background: Several studies suggest that CHF is accompanied by a
      reduced arterial Dist. METHODS: We measured diameter in radial artery, carotid
      artery (CA) and abdominal aorta (AO) by echotracking. Distensibility was obtained
      by relating it to blood pressure. Data were collected in 30 patients with CHF
      (New York Heart Association functional class I to III) under standard treatment
      with diuretic, digitalis and angiotensin-converting enzyme (ACE) inhibitor in
      whom CHF severity was assessed by maximum oxygen consumption (VO(2)max)
      percentage and in 30 age- and gender-matched controls. Patients with CHF were
      then randomized to maintain standard treatment (n = 10), double the ACE inhibitor
      dose (n = 10) or add an angiotensin II antagonist (n = 10) and restudied after
      two months. RESULTS: Distensibility was markedly reduced in the CHF group in all
      three vessels (p < 0.01), CA and AO Dist being related to CHF severity (p <
      0.05). After two months, Dist did not change in the group maintained under
      standard treatment, but it increased significantly (p < 0.05) and similarly when
      the ACE inhibitor dose was doubled or an angiotensin II antagonist was added.
      CONCLUSIONS: Congestive heart failure is characterized by a reduction of Dist of
      large-elastic and middle-sized muscular arteries. The reduction of large-elastic
      artery Dist is related to the CHF severity. These alterations can be reversed by
      drugs, effectively interfering with the renin-angiotensin system either at the
      ACE or at the angiotensin receptor level.

PMID- 11955845
TI  - Repeated assessment of coronary flow velocity pattern in patients with first
      acute myocardial infarction.
AB  - OBJECTIVES: The aim of this study was to evaluate the coronary blood flow
      velocity pattern immediately and 24 h after percutaneous transluminal coronary
      angioplasty (PTCA) for acute myocardial infarction (AMI) in relation to
      myocardial reperfusion and follow-up left ventricular (LV) function. BACKGROUND:
      Analysis of coronary blood flow velocity pattern after AMI may provide
      information about microvascular damage and the occurrence of a reperfusion
      injury. METHODS: Measurement of coronary blood flow velocity pattern was
      performed immediately after PTCA and after 24 h in 25 patients with first AMI
      using a Doppler guidewire. Measurements were related to reperfusion determined by
      intravenous myocardial contrast echocardiography (MCE) performed before PTCA and
      at 24 h and to LV function at four weeks. RESULTS: Using MCE, 13 patients showed
      reperfusion and 12 patients showed nonreperfusion. Compared with patients with
      reperfusion, patients with MCE nonreperfusion had a lower systolic peak flow
      velocity immediately after PTCA (10.0 +/- 0.3 cm/s vs. 19.3 +/- 0.8 cm/s,
      respectively) and after 24 h (12.3 +/- 0.4 cm/s vs. 21.3 +/- 0.1 cm/s,
      respectively, p = 0.0022), more frequent early systolic retrograde flow (6/12 vs.
      0/13, p = 0.0052 immediately after PTCA and 24 h later) and a shorter diastolic
      deceleration time immediately after PTCA (483 +/- 6 ms vs. 737 +/- 0 ms,
      respectively) and after 24 h (551 +/- 9 ms vs. 823 +/- 2 ms, respectively, p =
      0.0091). Similarly, patients with impaired LV function at four weeks had altered
      coronary flow pattern compared with patients with preserved function. The
      coronary flow velocity pattern showed a tendency for improvement after 24 h in
      the reperfusion and the nonreperfusion groups. CONCLUSIONS: The coronary flow
      velocity pattern immediately and 24 h after PTCA for AMI relates to myocardial
      perfusion determined by MCE and LV function at four weeks. The flow velocity
      pattern shows slight improvement during the first 24 h after revascularization,
      indicating the absence of a major reperfusion injury.

PMID- 11955846
TI  - The impact of lesion length and reference vessel diameter on angiographic
      restenosis and target vessel revascularization in treating in-stent restenosis
      with radiation.
AB  - OBJECTIVES: The study assessed the influence of lesion length and reference
      vessel diameter (RVD) on recurrent restenosis after gamma intracoronary radiation
      therapy (ICRT) for in-stent restenosis (IRS). BACKGROUND: Intracoronary radiation
      therapy reduces angiographic and clinical restenosis in patients with ISR. The
      impact of ICRT on challenging subgroups, such as long lesions and small vessels,
      has not been established. METHODS: Six-month quantitative coronary angiography
      and clinical follow-up were conducted to evaluate the influence of lesion length
      and RVD in patients with ISR treated with ICRT who were enrolled in gamma
      radiation trials. Angiographic binary restenosis (>50% diameter stenosis) and
      clinical events were assessed in 311 patients treated with gamma ICRT and 105
      patients who received placebo. RESULTS: Baseline demographic, angiographic and
      procedural details were similar in the two treatment groups. The ICRT group had
      reduced binary restenosis in vessels of all sizes (30% vs. 66%, p < 0.001), with
      the most benefit seen in small vessels. A trend toward reduced restenosis with
      ICRT was found across all lesion lengths. At six months, major adverse cardiac
      events (MACE) were reduced in the ICRT group compared to placebo (34% vs. 71%, p
      < 0.0001), driven by reduced target vessel revascularization (27% vs. 71%, p <
      0.0001). The independent predictors of angiographic restenosis include ICRT (OR
      [odds ratio] 0.16; CI [confidence interval] 0.10 to 0.28, p < 0.001), lesion
      length (OR 1.03; CI 1.01 to 1.05, p = 0.004) and RVD (OR 0.40; CI 0.23 to 0.67, p
      < 0.001). CONCLUSIONS: Intracoronary radiation therapy, compared to placebo,
      results in a significant reduction of angiographic restenosis across all vessel
      sizes, with a trend toward reduction of angiographic restenosis across all lesion
      lengths; this effect is seen predominantly in small vessels and diffuse lesions.

PMID- 11955847
TI  - Efficacy and safety of percutaneous treatment of iatrogenic femoral artery
      pseudoaneurysm by biodegradable collagen injection.
AB  - OBJECTIVES; The goal of this study was to assess the safety and efficacy of
      femoral artery pseudoaneurysm (FAP) closure by collagen injection. BACKGROUND;
      The FAP is an infrequent but troublesome complication after percutaneous
      transfemoral catheter procedures. If ultrasound-guided compression repair (UGCR)
      fails, vascular surgery is indicated. We have developed a less invasive method to
      close FAPs percutaneously by injecting collagen and, thus, inducing clotting
      within the aneurysm. METHODS: Via a 9F needle or 11F sheath, a biodegradable
      adhesive bovine collagen is injected percutaneously into the FAP, guided by
      angiography from the contralateral site. RESULTS: From 1993 to 2000, compression
      and UGCR had failed to obliterate 110 FAPs. These patients have been treated by
      collagen injection. Mean age of the patients was 65.6 +/- 10.2 years (range: 32
      to 85 years), and 50% were women. Immediate closure of the FAP was achieved in
      107/110 patients (97.3%) without any complication or adverse effect. In one
      patient the collagen could not be applied due to unfavorable anatomy. One patient
      needed a second session of collagen injection. In one patient too much collagen
      was inserted, which resulted in external compression of the artery, and surgical
      intervention was required. The overall success rate was 108/110 (98%, 95%
      confidence interval: 93.5% to 99.8%). Among the patients with successful
      procedures, there were no recurrences during six months follow-up. CONCLUSIONS:
      The percutaneous treatment of iatrogenic FAP, by injection with collagen, is an
      effective and safe strategy. This method provides an excellent therapeutic
      alternative to the traditional surgical management.

PMID- 11955848
TI  - Near-infrared spectroscopic characterization of human advanced atherosclerotic
      plaques.
AB  - OBJECTIVES; Living human carotid atherosclerotic plaques were examined in vitro
      by near-infrared (NIR) spectroscopy to determine the spectral features of plaque
      vulnerability. BACKGROUND: Plaque disruption, a major cause of heart attacks and
      strokes, cannot generally be predicted, but is thought to depend mainly on plaque
      composition. Near-infrared spectroscopy has been used to detect components in
      tissues noninvasively. METHODS: Using an NIR spectrometer fitted with a
      fiberoptic probe, living human carotid atherosclerotic plaques (from 25 patients)
      were examined ex vivo for plaque vulnerability. The plaques were cut into smaller
      sections according to their gross pathologic features, and NIR measurements were
      done at 20 degrees C, usually within 10 min. RESULTS: According to the American
      Heart Association's recommended classification scheme, the lesions were
      classified into three groups: the first group comprised of vulnerable type V/VI
      lesions; the second group, stable type I/II lesions; and the third (intermediate)
      group, mainly type III/IV lesions. Cluster analysis of the specimens' NIR spectra
      identified three major composition groups in each of the three NIR spectral
      regions: 2,200 to 2,330 nm, 1,620 to 1,820 nm and 1,130 to 1,260 nm. Calculation
      of the lipid/protein ratios in each group at two NIR regions (2,200 to 2,330 nm)
      revealed ratios of 1.49 +/- 1.20, 2.12 +/- 1.00 and 3.37 +/- 0.88 for type I/II,
      type III/IV and advanced type V/VI lesions, respectively (p < 0.03). At 1,620 to
      1,820 nm, the respective ratios for these histologic groups were 0.57 +/- 0.21,
      1.54 +/- 0.46 and 2.40 +/- 0.44 (p < 0.00003). CONCLUSIONS: The good ex vivo
      discrimination of histologically vulnerable and stable plaques in this study
      suggests that NIR spectroscopy has the potential to identify vulnerable
      atherosclerotic plaques in vivo.

PMID- 11955850
TI  - Sudden death in patients with implantable cardioverter defibrillators: the
      importance of post-shock electromechanical dissociation.
AB  - OBJECTIVES: The purpose of this study was to determine the mechanisms of sudden
      death (SD) in patients with ventricular tachyarrhythmias (ventricular
      tachycardia/ventricular fibrillation [VT/VF]) treated with an implantable
      cardioverter defibrillator (ICD). BACKGROUND: Despite ICD therapy, some patients
      with VT/VF still die suddenly. Optimal ICD use requires determination of the
      mechanisms of these residual SDs. METHODS: We reviewed 320 patient deaths during
      trials of Medtronic transvenous ICD systems (Medtronic Inc., Minneapolis,
      Minnesota). Sudden deaths were further categorized according to mechanism. Post
      shock electromechanical dissociation (EMD) describes a scenario where VT/VF was
      appropriately detected and treated by an ICD shock that restored a physiologic
      rhythm, but death still occurred immediately by EMD. RESULTS: A mode of death
      could be ascribed for 317 patients-90 (28%) were sudden, 156 (49%) were non
      sudden cardiac, and 71 (22%) were noncardiac. A mechanism of SD was proposed for
      68 patients-20 (29%) had post-shock EMD, 17 (25%) had VT/VF uncorrected by
      shocks, 11 (16%) had primary electromechanical dissociation, 9 (13%) had
      incessant VT/VF, 5 (7%) had VT/VF after their ICD was deactivated or removed, and
      6 (9%) had single instances of various other terminal events. Only New York Heart
      Association functional class independently predicted SD by post-shock EMD.
      CONCLUSIONS: The most common mechanism of SD in patients with an ICD is VT/VF
      treated with an appropriate shock followed by EMD. As this mechanism accounted
      for 29% of the SDs to which a cause could be ascribed, this mechanism of SD
      warrants further investigation.

PMID- 11955849
TI  - The presence of African American race predicts improvement in coronary
      endothelial function after supplementary L-arginine.
AB  - OBJECTIVES: The purpose of our study was to determine if the presence of African
      American ethnicity modulates improvement in coronary vascular endothelial
      function after supplementary L-arginine. BACKGROUND: Endothelial dysfunction is
      an early stage in the development of coronary atherosclerosis and has been
      implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration
      of endothelial dysfunction has been demonstrated in patients with established
      coronary atherosclerosis or with risk factors in response to infusion of L
      arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine
      responsiveness have not, heretofore, been studied. METHODS: Invasive testing of
      coronary artery and microvascular reactivity in response to graded intracoronary
      infusions of acetylcholine (ACh) +/- L-arginine was carried out in 33 matched
      pairs of African American and white subjects with no angiographic coronary artery
      disease. Pairs were matched for age, gender, indexed left ventricular mass, body
      mass index and low-density lipoprotein cholesterol. RESULTS: In addition to the
      matching parameters, there were no significant differences in peak coronary blood
      flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh
      before L-arginine infusion. However, absolute percentile improvement in CBF
      response to ACh infusion after L-arginine, as compared with before, was
      significantly greater among African Americans as a group (45 +/- 10% vs. 4 +/-
      6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase
      was mediated through further reduction in coronary microvascular resistance. L
      arginine infusion also resulted in greater epicardial dilator response after ACh
      among African Americans. CONCLUSIONS: We conclude that intracoronary infusion of
      L-arginine provides significantly greater augmentation of endothelium-dependent
      vascular relaxation in those of African American ethnicity when compared with
      matched white subjects drawn from a cohort electively referred for coronary
      angiography. Our findings suggest that there are target populations in which
      supplementary L-arginine may be of therapeutic benefit in the amelioration of
      microvascular endothelial dysfunction. In view of the excess prevalence of
      cardiomyopathy among African Americans, pharmacologic correction of
      microcirculatory endothelial dysfunction in this group is an important area of
      further investigation and may ultimately prove to be clinically indicated.

PMID- 11955851
TI  - Action potential duration restitution kinetics in human atrial fibrillation.
AB  - OBJECTIVES: We undertook this study to determine whether human atrial
      fibrillation (AF) relates to steeply sloped action potential duration restitution
      (APDR) kinetics and whether the spatial nonuniformity of APDR promotes
      persistence of AF. BACKGROUND: A steeply sloped APDR curve is known to be an
      important determinant of the induction of more complex action potential duration
      (APD) dynamics and fibrillation. METHODS: Patients with chronic atrial
      fibrillation (CAF) (n = 18), paroxysmal atrial fibrillation (PAF) (n = 14) and
      normal control subjects (n = 9) were studied. The monophasic action potential
      duration at 90% repolarization (APD(90)) and the effective refractory period
      (ERP) were measured at six sites in the right atrium. After AF was electrically
      converted, APDR was assessed by delivering a single extrastimulus after a train
      of stimuli at a cycle length of 600 ms (S(1)S(2)) at six different sites of the
      right atrium, as well as rapid pacing at cycle lengths that induced APD
      alternans. RESULTS: The APD(90) and ERP in patients with CAF were shorter than
      those in patients with PAF and control subjects (p < 0.05); however, the
      dispersions of APD(90) and ERP in each group were similar. The maximal slopes of
      APDR by S(1)S(2) and rapid pacing in patients with CAF (1.2 +/- 0.4 and 1.7 +/-
      0.2) and PAF (1.1 +/- 0.4 and 1.3 +/- 0.4) were higher than those in control
      subjects (0.5 +/- 0.3 and 0.8 +/- 0.2, respectively; p < 0.01). The maximal slope
      obtained by S(1)S(2) did not differ from that obtained by rapid pacing in any
      group. The inter-regional difference of the maximal slope in patients with CAF
      (1.6 +/- 0.4, p < 0.05) was greater than that in patients with PAF (1.2 +/- 0.3,
      p = NS vs. control) and control subjects (0.4 +/- 0.2). CONCLUSIONS: Atrial
      fibrillation was related to steeply sloped (>1) APDR kinetics. The spatial
      dispersion of APDR in patients with chronic AF was greater than that of patients
      with paroxysmal AF and control subjects, indicating that the heterogeneity of
      APDR of the atrium plays an important role in the persistence of AF.

PMID- 11955852
TI  - Electrogram polarity reversal as an additional indicator of breakthroughs from
      the left atrium to the pulmonary veins.
AB  - OBJECTIVES: We assessed the anatomical distribution and electrogram
      characteristics of breakthrough from the left atrium (LA) to the pulmonary veins
      (PVs). BACKGROUND: Localization of LA-PV breakthrough is an important technique
      for PV ablation in patients with atrial fibrillation (AF). METHODS: A total of
      157 patients with paroxysmal AF underwent PV disconnection guided by mapping with
      a circumferential 10-electrode catheter. Radiofrequency (RF) current was
      delivered ostially at the site(s) of earliest activation (113 patients) or
      electrogram polarity reversal defined by opposite polarity across adjacent
      bipoles (44 patients). Breakthrough sites were proved by changes in pulmonary
      vein potential activation sequence occurring as a result of localized RF delivery
      and were classified into four segments around the ostium (top, bottom, anterior,
      posterior). Results of mapping and ablation were compared between the two groups.
      RESULTS: A total of 99% of 411 targeted PVs were successfully disconnected in
      both groups. Breakthroughs were most frequent at the bottom of superior PVs (85%
      prevalence) and the top of inferior PVs (75% prevalence). A wide activation front
      (>5 synchronous bipoles) indicating broad breakthrough was observed in 18% of
      PVs. Polarity reversal occurred with 88% sensitivity and 91% specificity at
      breakthrough sites. Polarity reversal was restricted to fewer bipoles (2.0 +/-
      0.4 bipoles vs. 3.4 +/- 2.0 bipoles, p < 0.01) compared with earliest activation.
      Shorter RF application time was required to disconnect PVs with wide synchronous
      activation using polarity reversal compared with using conventional earliest
      activity (10.3 +/- 3.0 min vs. 12.3 +/- 3.4 min, p < 0.05). CONCLUSIONS: Bipolar
      electrogram polarity reversal allows more precise localization of breakthrough
      compared with the earliest activation, particularly in cases of wide synchronous
      PV activation.

PMID- 11955853
TI  - Outcome after abnormal exercise echocardiography for patients with good exercise
      capacity: prognostic importance of the extent and severity of exercise-related
      left ventricular dysfunction.
AB  - OBJECTIVES: We sought to define the prognostic implications of the extent and
      severity of exercise echocardiographic abnormalities in patients with good
      exercise capacity. BACKGROUND; The exercise capacity of patients with known or
      suspected coronary artery disease (CAD) is of prognostic importance, as is the
      extent of exercise-related left ventricular (LV) hypoperfusion or dysfunction.
      METHODS: We examined the outcomes of 1,874 patients with known or suspected CAD
      (mean age 64 +/- 10 years, 64% men) who had good exercise capacity (> or = 5
      metabolic equivalents [METs] for women, > or = 7 METs for men) but abnormal
      exercise echocardiograms and analyzed the potential association between clinical,
      exercise and echocardiographic variables and subsequent cardiac events. RESULTS:
      Multivariate predictors of time to cardiac death or nonfatal myocardial
      infarction (MI) were diabetes mellitus (risk ratio [RR] 1.88; 95% confidence
      interval [CI] 1.2 to 3.0), history of MI (RR 2.44; 95% CI 1.6 to 3.6) and an
      increase or no change in LV end-systolic size in response to exercise (RR 1.61;
      95% CI 1.1 to 2.5). Using echocardiographic variables that were of incremental
      prognostic value, we were able to stratify the cardiac risk of the study
      population; cardiac death or nonfatal MI rate per person-year of follow-up was
      1.6% for patients who had a decrease in LV end-systolic size in response to
      exercise (n = 1,330) and 1.2% for patients who did not have any severely abnormal
      LV segments immediately after exercise (n = 868). CONCLUSIONS: In patients with
      good exercise capacity, echocardiographic descriptors of the extent and severity
      of exercise-related LV dysfunction were of independent and incremental prognostic
      value. Stratification of patients into low- and higher risk subgroups was
      possible using these exercise echocardiographic characteristics.

PMID- 11955854
TI  - The "exercise" part of exercise echocardiography.

PMID- 11955855
TI  - Survival after aortic valve replacement for severe aortic stenosis with low
      transvalvular gradients and severe left ventricular dysfunction.
AB  - OBJECTIVE: We sought to assess whether aortic valve replacement (AVR) among
      patients with severe aortic stenosis (AS), severe left ventricular (LV)
      dysfunction and a low transvalvular gradient (TVG) is associated with improved
      survival. BACKGROUND: The optimal management of patients with severe AS with
      severe LV dysfunction and a low TVG remains controversial. METHODS: Between 1990
      and 1998, we evaluated 68 patients who underwent AVR at our institution (AVR
      group) and 89 patients who did not undergo AVR (control group), with an aortic
      valve area < or = 0.75 cm(2), LV ejection fraction < or = 35% and mean gradient <
      or = 30 mm Hg. Using propensity analysis, survival was compared between a cohort
      of 39 patients in the AVR group and 56 patients in the control group. RESULTS:
      Despite well-matched baseline characteristics among propensity-matched patients,
      the one- and four-year survival rates were markedly improved in patients in the
      AVR group (82% and 78%), as compared with patients in the control group (41% and
      15%; p < 0.0001). By multivariable analysis, the main predictor of improved
      survival was AVR (adjusted risk ratio 0.19, 95% confidence interval 0.09 to 0.39;
      p < 0.0001). The only other predictors of mortality were age and the serum
      creatinine level. CONCLUSIONS: Among select patients with severe AS, severe LV
      dysfunction and a low TVG, AVR was associated with significantly improved
      survival.

PMID- 11955856
TI  - Ventricular function in aortic stenosis: how low can you go?

PMID- 11955857
TI  - In vivo noninvasive detection and age definition of arterial thrombus by MRI.
AB  - OBJECTIVES: The purpose of this study was to evaluate the potential of magnetic
      resonance (MR) to detect arterial thrombotic obstruction and define thrombus age.
      BACKGROUND; Arterial thrombi underlie the clinical consequences of
      atherosclerosis and are not reliably detected by current noninvasive diagnostic
      techniques. METHODS: Carotid thrombi were induced in swine (n = 7) by arterial
      injury. Serial high-resolution in vivo MR images were obtained using black-blood
      T1-weighted (T1W) and T2-weighted (T2W) sequences in a clinical 1.5T MR system at
      6 h, 1 day and at 1, 2, 3, 6 and 9 weeks. At each time point one animal was
      sacrificed and the occluded carotid artery processed for histopathology. Thrombus
      signal intensity (SI) was normalized to that of the adjacent muscle. Thrombus age
      was assessed based on MR appearance by two blinded independent observers.
      RESULTS: Thrombus appearance and relative SI revealed characteristic temporal
      changes in multicontrast-weighted MR images, reflecting histologic changes in the
      composition. Acute thrombus appeared very bright on the T2W images, facilitating
      the detection. Signal intensity was 197 +/- 25% at 6 h, peaking at 1 week (246 +/
      51%), reaching a plateau by 6 weeks (120 +/- 15%). At six weeks, complete
      thrombus organization was confirmed histologically. The T1W images had similar
      pattern with lower SI than T2W. Age definition using visual appearance was highly
      accurate (Pearson's chi-square with 4 df ranging from 96 to 132 and Cohen's kappa
      at 0.81 to 0.94). Agreement between observers was substantial (Pearson chi-square
      with 4 df = 91.5, kappa = 0.79). CONCLUSIONS: Magnetic resonance imaging is a
      promising tool to noninvasively detect arterial thrombosis. Measurement of SI and
      the characteristic visual appearance of the thrombus have the potential to define
      thrombus age.

PMID- 11955858
TI  - Angiotensin II receptor blockade does not improve left ventricular function and
      remodeling in subacute mitral regurgitation in the dog.
AB  - OBJECTIVES: We hypothesized that angiotensin II type-1 (AT(1)) receptor blocker
      (AT(1)RB) would prevent adverse left ventricular (LV) remodeling and LV
      dysfunction when started at the outset of mitral regurgitation (MR). BACKGROUND:
      Little is known regarding the efficacy of AT(1)RB treatment of MR. METHODS:
      Mitral regurgitation was induced by chordal disruption in adult mongrel dogs. Six
      normal dogs (NLs) were compared to six untreated MR dogs (MR) and seven dogs
      treated with the receptor blocker irbesartan (MR+AT(1)RB) started 24 h after
      induction of MR (60 mg/kg p.o. b.i.d.) and continued for three months. RESULTS:
      Treatment with AT(1)RB decreased systemic vascular resistance but did not
      significantly improve cardiac output, LV end-diastolic dimension (LVEDD) or
      LVEDD/wall thickness compared to untreated MR dogs. Resting isolated
      cardiomyocyte length increased in MR versus NLs and was further increased in
      AT(1)RB dogs. Left ventricular end-systolic dimension increased to a greater
      extent from baseline in AT(1)RB dogs versus untreated MR dogs (29 +/- 9% vs. 12
      +/- 6%, p < 0.05), despite a significantly lower LV peak systolic pressure in
      AT(1)RB dogs. Plasma-angiotensin (ANG) II was elevated greater than threefold in
      both MR and MR+AT(1)RB versus NLs. In contrast, intracardiac ANG II was increased
      greater than twofold in MR dogs versus NLs, but was normalized by AT(1)RB.
      CONCLUSIONS: The use of AT(1)RB decreased systemic vascular resistance and
      attenuated local expression of the renin-angiotensin system but did not prevent
      adverse LV chamber and cardiomyocyte remodeling. These results suggest that
      blockade of the AT(1) receptor does not improve LV remodeling and function in the
      early myocardial adaptive phase of MR.

PMID- 11955859
TI  - Inhibition of the renin-angiotensin system and the left ventricular adaptation to
      mitral regurgitation.

PMID- 11955861
TI  - Imaging of myocardial infarction: comparison of magnevist and gadophrin-3 in
      rabbits.
AB  - OBJECTIVES: This study was designed to determine the enhancement profile of a
      necrosis-specific contrast agent (gadophrin III) in comparison to a standard
      extracellular agent on T1-weighted magnetic resonance (MR) images in acute and
      chronic myocardial infarctions (MIs). BACKGROUND: Contrast-enhanced MR imaging
      demonstrated the ability to accurately quantify infarct size; however, some
      controversies persist about which contrast medium is best suited. METHODS:
      Fifteen rabbits underwent thoracotomy and permanent occlusion of a branch of the
      left coronary artery. Two animals died before imaging, eight were examined 48 h
      after occlusion and five animals were imaged six weeks following induction of
      infarction. All animals received 50 micromol/kg of gadophrin-3 24 h before the MR
      examination. Continuous short-axis views were collected using an inversion
      recovery turbo fast low angle shot sequence. Imaging was repeated 5 to 10 min
      following additional injection of 100 micromol/kg of Magnevist. The area of
      hyperenhancement demarcated following gadophrin-3 injection was compared with the
      region of hyperenhancement seen on gadophrin-3 plus Magnevist enhanced image
      using triphenyltetrazolium chloride (TTC) staining as the standard of reference.
      RESULTS: In acute MI the mean difference in size of hyperenhancement seen on the
      two different in vivo MR scans was -1.8 +/- 6.0 mm(2) (p > 0.05). Both
      measurements showed excellent agreement with TTC staining. Chronic MIs showed no
      enhancement with gadophrin-3, whereas application of Magnevist resulted in
      hyperenhancement. CONCLUSIONS; Standard extracellular contrast agents do not
      overestimate the size of acute MI. The combination of gadophrin-3 and Magnevist
      can distinguish acute and chronic myocardial injury because chronic MIs do not
      enhance with gadophrin-3.

PMID- 11955860
TI  - Excessive activation of matrix metalloproteinases coincides with left ventricular
      remodeling during transition from hypertrophy to heart failure in hypertensive
      rats.
AB  - OBJECTIVES: We sought to elucidate how the local activation of matrix
      metalloproteinases (MMPs) is balanced by that of the endogenous tissue inhibitors
      of MMP (TIMPs) during left ventricular (LV) remodeling. BACKGROUND: Although it
      is known that the extracellular matrix (ECM) must be altered during LV
      remodeling, its local regulation has not been fully elucidated. METHODS: In Dahl
      salt-sensitive rats with hypertension, in which a stage of concentric,
      compensated left ventricular hypertrophy (LVH) at 11 weeks is followed by a
      distinct stage of congestive heart failure (CHF) with LV enlargement and
      dysfunction at 17 weeks, we determined protein and messenger ribonucleic acid
      (mRNA) levels of LV myocardial TIMP-2 and -4 and MMP-2, as well as their
      concomitant activities. RESULTS: No changes were found at the LVH stage. However,
      during the transition to CHF, TIMP-2 and -4 activities, protein and mRNA levels
      were all sharply increased. At the same time, the MMP-2 mRNA and protein levels
      and activities, as determined by gelatin zymography, as well as by an antibody
      capture assay, showed a substantial increase during the transition to CHF. The
      net MMP activities were closely related to increases in LV diameter (r = 0.763)
      and to systolic wall stress (r = 0.858) in vivo. CONCLUSIONS: Both TIMPs and MMP
      2 remained inactive during hypertrophy, per se; they were activated during the
      transition to CHF. At this time, the activation of MMP-2 surpassed that of TIMPs,
      possibly resulting in ECM breakdown and progression of LV enlargement.

PMID- 11955862
TI  - Role of Fas/FasL pathway in the activation of infiltrating cells in murine acute
      myocarditis caused by Coxsackievirus B3.
AB  - OBJECTIVES: This study was designed to investigate the roles of Fas/FasL pathway
      in myocardial damage in murine acute myocarditis caused by Coxsackie virus B3
      (CVB3). BACKGROUND: Cardiac myocyte apoptosis rarely occurs in murine acute
      myocarditis caused by CVB3. Fas/FasL belong to the tumor necrosis factor
      receptor/ligand superfamily of costimulatory molecules and are known to play a
      critical role in the induction of apoptosis, as well as in the cytotoxicty
      mediated by T-cells and natural killer cells. METHODS: We first analyzed the
      expression of Fas on cardiac myocytes in vivo and in vitro. Second, we examined
      the development of myocardial damage, in C3H/He mice treated with an anti-FasL
      monoclonal antibody (mAb), and in C3H/He-lpr/lpr mice and C3H/He-gld/gld mice
      infected with CVB3. Third, to investigate the effects of anti-FasL mAb treatment
      on the activation of the infiltrating cells, we examined the expression of
      interferon (IFN)-gamma and interleukin (IL)-2 as activation markers in the heart
      of mice by semiquantitative polymerase chain reaction. RESULTS: Fas was markedly
      induced on cardiac myocytes with acute myocarditis. Myocardial inflammation was
      decreased in mice treated with anti-Fas L mAb, C3H/He-lpr/lpr mice and C3H/He
      gld/gld mice. Anti-FasL mAb-treatment also decreased the expression of IFN-gamma,
      IL-2, inducible nitric oxide synthase and CVB3 genomes in myocardial tissue.
      CONCLUSIONS: Our findings strongly suggested that the Fas/FasL pathway played a
      critical role in the development of massive myocardial necrosis through
      activation of infiltrating cells, and raise the possibility of immunotherapy by
      blocking the Fas/FasL pathway to prevent myocardial damage and improve the
      prognosis of patients with viral myocarditis.

PMID- 11955864
TI  - Late-onset primary LVH HCM versus cardiac fabry variant.

PMID- 11955863
TI  - Troponin T in acute coronary syndromes: mechanisms and management issues.

PMID- 11955873
TI  - Infections after corneal refractive surgery: can we do better?

PMID- 11955874
TI  - Posterior capsule opacification in 5.5 mm versus 6.0 mm AcrySof lenses.

PMID- 11955875
TI  - Enlargement of a preexisting capsulorhexis.

PMID- 11955877
TI  - Pars plana vitreous tap for phacoemulsification in the crowded eye.

PMID- 11955879
TI  - Pupillary capture technique.

PMID- 11955880
TI  - Use of the Fugo blade in complicated cases.

PMID- 11955881
TI  - Corneal endothelial cell density after trypan blue capsule staining in cataract
      surgery.

PMID- 11955882
TI  - Trypan-blue-assisted capsulorhexis for trainee phacoemulsification surgeons.

PMID- 11955883
TI  - Consultation section: cataract surgical problem.

PMID- 11955895
TI  - Floaterectomy: combined phacoemulsification and deep anterior vitrectomy.
AB  - We describe a 1-stage surgical technique to treat vitreous floaters.
      Phacoemulsification is combined with a deep anterior vitrectomy through a
      posterior curvilinear capsulorhexis followed by implantation of a posterior
      chamber intraocular lens. The technique was used in 10 eyes of 6 patients. Six
      months postoperatively, 8 eyes had a best corrected visual acuity (BCVA) of 6/6
      with complete resolution of symptoms. Two eyes of 1 patient developed cystoid
      macular edema that reduced final BCVA to 6/18 bilaterally. In this case, the
      floaters may have been the result of previously undiagnosed intermediate uveitis.

PMID- 11955896
TI  - Two-incision push-pull capsulorhexis for pediatric cataract surgery.
AB  - Pediatric capsulorhexis is a challenging surgical technique because of the
      elasticity of the pediatric anterior capsule. This technique of manual
      capsulorhexis allows reliable and reproducible results for the size and
      centration of anterior and posterior capsulorhexes in pediatric cases. The
      technique is a modification of a previously reported method.

PMID- 11955897
TI  - Modified technique using flexible iris retractors in clear corneal cataract
      surgery.
AB  - Flexible nylon iris retractors are a useful adjunct to cataract surgery in cases
      of small pupil. We present a modification of the standard technique. Instead of
      approaching the square-shaped pupil formed by iris retractors from the side, we
      recommend an approach anterior to 1 of the retractor hooks. From the surgeon's
      viewpoint, the pupil goes from a square shape to a diamond shape. This
      modification minimizes the likelihood of iris prolapse and iris damage during
      phacoemulsification and increases the workspace for the phacoemulsification
      needle.

PMID- 11955898
TI  - Cyclotorsion: a possible cause of residual astigmatism in refractive surgery.
AB  - PURPOSE: To determine whether cyclotorsion occurs when a subject changes from
      binocular to monocular fixation and to assess positionally induced cyclotorsion.
      SETTING: Clinics of the Rotterdam Eye Hospital, Rotterdam, The Netherlands.
      METHODS: The axis of astigmatism was measured with the Nidek handheld keratometer
      in 15 normal subjects under monocular and binocular fixation and in seated and
      supine positions. The limits of agreement for the repeatability of measurements
      with the Nidek keratometer were used to identify subjects with statistically
      significant cyclotorsion. RESULTS: Two subjects (13%) showed statistically
      significant excyclotorsion when changing from binocular to monocular fixation in
      a seated position. In a supine position, 3 subjects (20%) showed excyclotorsion
      when the fixation changed. Body position itself had no influence on ocular
      torsion. CONCLUSIONS: Significant cyclotorsion may occur under monocular viewing
      conditions. If monocular photorefractive keratectomy procedures are based on
      binocular keratometry readings, an undercorrection of myopic astigmatism may
      result. Individuals at risk should be identified before refractive keratectomy is
      performed.

PMID- 11955899
TI  - Correlation between refractive and measured corneal power changes after myopic
      excimer laser photorefractive surgery.
AB  - PURPOSE: To determine the correlation between the refractive and measured corneal
      power changes after myopic photorefractive surgery. SETTING: Department of
      Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. METHODS:
      Eighty-six eyes that had myopic photorefractive surgery were analyzed. The data
      included preoperative and 1-year postoperative subjective refraction, standard
      automated keratometry, and computerized videokeratography. Statistical analysis
      was performed to determine the relationship between the changes in subjective
      refraction in the corneal plane (Delta SEQco) and in 4 corneal power measurements
      including the power measured by automated keratometry (Delta Auto K), topographic
      simulated keratometric power (Delta Sim K), the power of the first
      photokeratoscopic ring on videokeratography (Delta Central K), and the average
      videokeratographic power on the pupil margin (Delta Pupil K). RESULTS: The
      measured corneal power always underestimated the Delta SEQco, with Delta SEQco >
      Delta Central K > Delta Sim K > Delta Pupil K > Delta Auto K. All the changes in
      measured corneal power could predict the Delta SEQco with more than 90.00%
      (90.19% to 92.31%) reliability at 1 year as calculated by the regression formulas
      (P <.001). The underestimation of measured corneal power changes was correlated
      with the amount of myopic correction, especially the Auto K (all P <.001).
      CONCLUSIONS: Direct corneal power measurements using automatic keratometry
      underestimated the actual corneal flattening after photorefractive surgery, which
      could be adjusted by a linear regression formula. Measuring the power of the
      first photokeratoscopic ring on videokeratography might provide a better
      estimation of actual corneal flattening after photorefractive surgery.

PMID- 11955900
TI  - Depth and age-dependent distribution of keratocytes in healthy human corneas: a
      study using scanning-slit confocal microscopy in vivo.
AB  - PURPOSE: To document keratocyte distribution and changes with age in the cellular
      network of the human cornea in vivo. SETTING: Department of Ophthalmology,
      University of Rostock, Rostock, Germany. METHODS: Forty-nine eyes of 31 healthy
      subjects of various ages were examined with a modified Microphthal scanning-slit
      confocal microscope (SSCM) (Hund) to document keratocyte distribution in the
      intact living cornea. Optical sections made by confocal microscopy were recorded
      on videotape, and the keratocyte density was determined for the total volume of
      the cornea and for the stromal sublayers. RESULTS: The highest cell density was
      in the anterior stroma of the cornea immediately posterior to Bowman's membrane
      (24 320 cells/mm(3) +/- 6740 [SD]), the lowest in the central area (11,610 +/-
      4290 cells/mm(3)), and an intermediate density in the posterior stroma
      immediately adjacent to Descemet's membrane (18,850 +/- 4610 cells/mm(3)). The
      differences were statistically significant (P <.005). The keratocyte density was
      significantly lower in the anterior and posterior regions in the group older than
      50 years: Cell density at 4% depth was 20,960 +/- 8200 cells/mm(3) and at 96%, 15
      520 +/- 4290 cells/mm(3) (P <.05). CONCLUSIONS: In healthy living corneas, the
      keratocyte density was high in the areas adjacent to Bowman's and Descemet's
      membranes and was lower in patients older than 50 years than in those younger
      than 50 years. Further studies are needed to document the rate of change with age
      and to better understand the role and capacity of aging keratocytes in
      regenerative processes following corneal diseases or surgical procedures.

PMID- 11955901
TI  - Intraocular pressure after bilateral cataract surgery using Healon, Healon5, and
      Healon GV.
AB  - PURPOSE: To determine whether there is a difference in frequency or severity of
      postoperative intraocular pressure (IOP) spikes after bilateral
      phacoemulsification with complete ophthalmic viscosurgical device (OVD) removal
      when Healon5 (sodium hyaluronate 2.3%), Healon (sodium hyaluronate 1%), or Healon
      GV (sodium hyaluronate 1.4%) is used. SETTING: York Finch Eye Associates and
      Humber River Regional Hospital, Toronto, Ontario, Canada. METHODS: Bilateral
      cataract surgery was performed in 99 patients; 50 were randomly assigned to
      receive Healon5 in 1 eye and Healon GV in the fellow eye and 49, Healon in 1 eye
      and Healon GV in the fellow eye. The IOP was measured preoperatively as well as 5
      and 24 hours and 7 days postoperatively. The mean IOP and standard deviation at
      each time interval were calculated for each OVD. The results were compared among
      the OVDs using Student t tests for each time at which IOP was assessed. RESULTS:
      There were no significant differences in postoperative IOP spikes among the
      Healon5, Healon, and Healon GV groups; however, patients receiving lower
      viscosity OVDs had a lower mean IOP at 24 hours. All groups had increased IOP at
      5 and 24 hours and reduced IOP at 7 days. CONCLUSIONS: Within a family of
      molecularly similar OVDs, lower viscosity OVDs appear to cause slightly lower
      mean elevations in IOP in normal patients at 24 hours. However, if the OVD is
      removed, postoperative IOP spikes above 21 mm Hg appear related more to patient
      factors (eg, predisposition in glaucoma patients) and surgically induced trauma
      than to the specific long-chain non-cross-linked hyaluronan OVD used.

PMID- 11955902
TI  - Effect of cataract surgery on the progression of diabetic retinopathy.
AB  - PURPOSE: To study the effect of cataract surgery and other factors on the
      progression of diabetic retinopathy using the nonoperated contralateral eye as a
      control. SETTING: Department of Ophthalmology, Catholic University Medical
      College, Uijongbu St. Mary's Hospital, Seoul, Korea. METHODS: Monocular cataract
      surgery was performed in 75 patients who had the same degree of retinopathy or no
      retinopathy in both eyes preoperatively. Patients were assigned to 1 of 2 groups
      as follows: Group A, progression of retinopathy in the operated eye caused by
      cataract surgery; Group B, no progression of retinopathy bilaterally, comparable
      level of progression in both eyes, or more progression of retinopathy in the
      nonoperated eye than in the operated eye. The differences between the 2 groups in
      age, duration of and treatment methods for diabetes, renal function, and presence
      of preoperative macular edema were compared. The 1-year follow-up included
      evaluation of the progression of retinopathy. RESULTS: Surgery caused the
      retinopathy to progress in 23 patients (30.6%, Group A); 52 patients (69.4%,
      Group B) had no progression of retinopathy or a comparable level of retinopathy
      postoperatively. The operated eye had more progression of retinopathy than the
      nonoperated contralateral eye (P <.05). There was no significant difference
      between the 2 groups in age, diabetes duration, surgical method, or hypertension.
      Preoperative macular edema and poor renal function significantly affected the
      progression of diabetic retinopathy after cataract surgery (P <.05). CONCLUSIONS:
      Diabetic retinopathy progressed after cataract surgery. The presence of
      preoperative macular edema and poor renal function increased the progression of
      retinopathy postoperatively.

PMID- 11955903
TI  - Topical versus retrobulbar anesthesia for combined phacotrabeculectomy:
      prospective randomized study.
AB  - PURPOSE: To compare the safety and efficacy of topical and retrobulbar anesthesia
      for combined phacotrabeculectomy. SETTING: Tertiary-care university hospital
      ambulatory surgical center. METHODS: In this prospective study, 40 consecutive
      patients having combined phacotrabeculectomy were randomized to receive topical
      (n = 20) or retrobulbar (n = 20) anesthesia. Operating conditions, patient
      comfort, and surgical outcome were evaluated. RESULTS: There was no significant
      between-group difference in operating conditions (P =.56), pain during (P =.41)
      or after (P =.23) surgery, or supplemental anesthesia required (P =.49). Few
      patients in either group were bothered by tissue manipulation or the microscope
      light, although more patients in the topical group were slightly bothered by
      touch sensation (P =.05). Chemosis, subconjunctival hemorrhage, and eyelid
      hematoma were seen almost exclusively in the retrobulbar group (P <.05).
      Inadvertent eye movement was present more frequently in the topical group (P
      =.04), although this did not pose a problem to the surgeon. CONCLUSION: Topical
      anesthesia is a safe and effective alternative to retrobulbar anesthesia for
      combined phacotrabeculectomy.

PMID- 11955905
TI  - Biocompatibility of hydrophilic intraocular lenses.
AB  - PURPOSE: To assess the biocompatibility of 3 hydrophilic acrylic intraocular
      lenses (IOLs) by evaluating the postoperative cell reaction on the IOL surface,
      anterior capsule opacification (ACO) rate, and presence of membrane growth over
      the anterior IOL surface. SETTING: University Eye Clinic of Trieste, Trieste,
      Italy. METHODS: In this prospective study, 73 patients were randomized to receive
      1 of 3 types of hydrogel IOLs after phacoemulsification: Storz Hydroview H60M,
      Corneal ACR6D, or Ioltech Stabibag. To analyze and photograph the anterior IOL
      surface, slitlamp biomicroscopy and specular microscopy were performed 7, 30, 90,
      and 180 days after surgery. Small, epithelioid, and giant inflammatory cell
      reaction was evaluated. In addition, ACO and membrane growth on the anterior IOL
      surface were assessed. RESULTS: Low inflammatory cell adhesion was observed on
      the anterior surface of all 3 IOLs. The Stabibag group had a significantly higher
      grade of small inflammatory cell reaction 7 and 30 days after surgery. A
      significantly higher rate of ACO was observed in the ACR6D group. The Hydroview
      and ACR6D groups had a significantly higher percentage of membrane growth from
      the capsulorhexis edge onto the anterior IOL surface than the Stabibag group.
      CONCLUSIONS: Clinically, the 3 hydrophilic IOLs behaved in a different manner,
      showing the different forms of biocompatibility. Results indicate that a
      different chemical composition determines correspondingly different protein
      absorption on IOL surfaces. This might result in a different adhesion pattern and
      spreading of lens epithelial and inflammatory cells.

PMID- 11955904
TI  - Long-term endothelial cell loss after phacoemulsification: peribulbar anesthesia
      versus intracameral lidocaine 1%: prospective randomized clinical trial.
AB  - PURPOSE: To evaluate endothelial cell loss after phacoemulsification with
      posterior chamber intraocular lens implantation using peribulbar anesthesia or
      topical anesthesia combined with intracameral unpreserved lidocaine 1%. SETTING:
      Department of Ophthalmology, Charite, Humboldt-University of Berlin, Berlin,
      Germany. METHODS: Before and 20 months +/- 5.1 (SD) after surgery, specular
      microscopy was used to evaluate the number and morphology of endothelial cells in
      78 eyes having peribulbar anesthesia or topical anesthesia combined with an
      intracameral injection of 0.15 cc unpreserved lidocaine 1%. RESULTS: The mean
      endothelial cell loss was 11.11% in the peribulbar group and 12.55% in the
      topical/lidocaine group. There was no statistically significant difference in the
      amount of endothelial cell loss or cell morphology between the 2 groups.
      CONCLUSION: The long-term postoperative endothelial cell course showed that
      topical anesthesia combined with an intracameral injection of 0.15 cc unpreserved
      lidocaine 1% is a safe alternative to peribulbar anesthesia.

PMID- 11955906
TI  - Preliminary results of cataract extraction with implantation of a single-piece
      AcrySof intraocular lens.
AB  - PURPOSE: To evaluate the intraoperative and postoperative performance of the
      single-piece AcrySof SA30AL intraocular lens (IOL) in a series of patients after
      cataract surgery and IOL implantation. SETTING: Department of Ophthalmology and
      Neurosurgery, University of Siena, Siena, Italy. METHODS: In this prospective
      study, 20 patients who had phacoemulsification and implantation of a single-piece
      AcrySof SA30AL lens from March to April 2000 were evaluated. Assessed were
      control of IOL folding, ease of IOL implantation, IOL centration, intraoperative
      and postoperative complications, visual acuity, and anterior (ACO) and posterior
      (PCO) capsule opacification. RESULTS: In all cases, the IOL was easily folded,
      inserted, and unfolded. It remained well centered in the capsular bag, and there
      were no intraoperative or postoperative complications. The best corrected visual
      acuity after surgery was 20/40 or better in all patients. No eye developed ACO or
      phimosis. One eye had a well-demarcated, oval area of lens epithelial cell
      proliferation on the posterior capsule that did not impair visual acuity.
      CONCLUSIONS: Initial results indicate that the single-piece AcrySof SA30AL IOL
      has good biocompatibility, haptic flexibility and resistance, and stability in
      the capsular bag. The incidence of PCO in 1 eye could have been the result of
      several factors and requires further evaluation. An area of future study is the
      wide haptic of the lens, which may create a path for cells to proliferate as they
      travel from the equatorial capsule.

PMID- 11955907
TI  - Significant postoperative refractive errors in vivo with the Mentor Memorylens
      intraocular lens.
AB  - PURPOSE: To determine the difference between the predicted and postoperative
      refraction in eyes after implantation of the Mentor MemoryLens intraocular lens
      (IOL) and compare these results with those of 2 other types of foldable IOLs
      implanted by the same surgeons. SETTING: Community-based group practice
      ophthalmology clinic. METHODS: All operated eyes (341) of all patients who had
      routine phacoemulsification with implantation of a MemoryLens IOL performed by 1
      of 2 surgeons were evaluated retrospectively. The predicted refractive error and
      actual postoperative refractive error were compared in each eye in the MemoryLens
      group and in 2 smaller control groups with an AcrySof acrylic (Alcon) or SI-40
      silicone (Allergan Medical Optics) IOL implanted by the same surgeons using
      identical technique and IOL calculation parameters. Patients in whom the
      difference between the predicted and actual postoperative refraction fell
      significantly outside expected parameters were rechecked with repeat axial length
      and keratometric readings, and these measurements were used to back-calculate the
      effective in vivo IOL power. RESULTS: The MemoryLens group had significantly
      greater variability in postoperative refractive results from those predicted by
      the Hoffer program than the 2 control groups. The postoperative refractive error
      in the MemoryLens group differed from +1.50 to -5.50 diopters (D) from that
      predicted by the IOL calculation formulas. When the outlier groups (ie, greater
      than +0.50 D or less than -1.00 D from predicted refractive error) were evaluated
      and compared to the rest of the MemoryLens group and the 2 control groups, no
      significant difference in axial length, keratometric measurements, operative
      surgeon, surgical technique, or patient age was found. Repeat axial length and
      keratometric measurements in the outlier group were not significantly different
      from those in the same eyes preoperatively. Back-calculation using postoperative
      axial length and keratometric measurements in the highly myopic outlier group
      showed that the mean difference between the labeled IOL power and actual in vivo
      IOL power in the outlier group was -3.08 D (range -1.98 to -7.54 D). The best
      corrected visual acuity was not affected in patients in the outlier groups
      despite the refractive variability. CONCLUSION: The variation in postoperative
      refractive results in the MemoryLens group was significantly greater than in the
      2 other foldable IOL groups.

PMID- 11955908
TI  - Relationship of AcrySof acrylic and PhacoFlex silicone intraocular lenses to
      visual acuity and posterior capsule opacification.
AB  - PURPOSE: To compare the changes in visual acuity and the development of posterior
      capsule opacification (PCO) with AcrySof acrylic intraocular lenses (IOLs) (Alcon
      Laboratories) and second-generation PhacoFlex silicone IOLs (Allergan ). SETTING:
      Eye Associates of New Mexico and Southwest Colorado, Albuquerque, New Mexico,
      USA. METHODS: Medical charts of patients having cataract extraction with
      implantation of an AcrySof MA30BA or MA60BM (MA30/60) or PhacoFlex SI-30NB or SI
      40NB (SI-30/40) IOL between January 1995 and June 1997 were abstracted. Analyzed
      were the changes in visual acuity and development of PCO 1 month postoperatively
      and at the last available ophthalmologist visit or the visit before neodymium:YAG
      (Nd:YAG) capsulotomy. RESULTS: Patients with MA30/60 acrylic IOLs were
      significantly older, had a worse preoperative best corrected visual acuity
      (BCVA), and had more concomitant ocular diseases than those with SI-30/40
      silicone IOLs. The change in BCVA from preoperatively to 1 month postoperatively
      was equivalent in the 2 lens groups. The BCVA declined from 1 month
      postoperatively to the last recorded or pre-Nd:YAG visit. This decline was
      greater in eyes with SI-30/40 silicone IOLs than in those with MA30/60 acrylic
      IOLs. Although the decrease in BCVA between IOL types was not significantly
      different, eyes with a SI-30/40 silicone IOL were significantly more likely to
      develop PCO and have Nd:YAG capsulotomy. Eyes developing PCO had a statistically
      significant decline in BCVA from 1 month postoperatively to the last/pre-Nd:YAG
      visit. CONCLUSIONS: The MA30/60 acrylic lenses were associated with lower PCO and
      Nd:YAG capsulotomy rates than second-generation SI-30/40 silicone IOLs. Patients
      with MA30/60 IOLs also tended to have less of a decrease in visual acuity than
      patients with SI-30/40 silicone lenses, probably as a result of the difference in
      PCO rates between groups.

PMID- 11955909
TI  - Effect of laser in situ keratomileusis on retinal nerve fiber layer thickness
      measurements by scanning laser polarimetry.
AB  - PURPOSE: To determine the effect of laser in situ keratomileusis (LASIK) on
      retinal nerve fiber layer measurements by scanning laser polarimetry in a large
      clinical trial. SETTING: Asan Medical Center, University of Ulsan, Department of
      Ophthalmology, Seoul, Korea. METHODS: Scanning laser polarimetry measurements
      were performed in 59 eyes of 59 consecutive patients who had LASIK. The mean
      retardation values of the whole measurement ellipse and of the superior,
      inferior, temporal, and nasal sectors of the ellipse before and after LASIK were
      compared statistically. RESULTS: The mean spherical equivalent refractive error
      was -6.10 diopters (D) +/- 2.34 (SD) (range -1.19 to -15.50 D) preoperatively and
      -0.31 +/- 0.52 D (range +0.68 to -2.13 D) postoperatively. The mean ablation
      depth was 94.0 +/- 30.49 microm (range 28.0 to 161.1 microm). The mean
      postoperative retardation values of all the sectors and of the superior,
      temporal, inferior, and nasal sectors showed reduced nerve fiber layer thickness
      (P =.000, P =.000, P =.011, P =.000, and P=.002, respectively). CONCLUSION: Laser
      in situ keratomileusis affected nerve fiber layer thickness measurements by
      scanning laser polarimetry. The change in nerve fiber layer thickness was
      probably due to modification of the corneal architecture. This effect of
      keratorefractive surgery should be considered when using scanning laser
      polarimetry as a diagnostic and follow-up tool for glaucoma.

PMID- 11955910
TI  - Reversibility and exchangeability of intrastromal corneal ring segments.
AB  - PURPOSE: To evaluate the effect of removal and/or exchange of intrastromal
      corneal ring segments (ICRS, Intacs); specifically the risk factors, degree of
      reversibility, and visual outcomes. SETTING: Gimbel Eye Centres, Calgary,
      Edmonton, and Vancouver, Canada. METHODS: Prospective cohort data were collected
      on 71 eyes that had ICRS placement by 3 surgeons at the Gimbel Eye Centres
      between August 1998 and July 1999. Data included patient symptoms, best spectacle
      corrected visual acuity, uncorrected visual acuity (UCVA), manifest refraction,
      reason for removal or replacement, keratometry, corneal topography, and
      complications. RESULTS: Twenty-four eyes (33.8%) had exchange or removal
      procedures because of underresponse, 20 eyes; overresponse, 2 eyes; and induced
      astigmatism and shallow placement, 1 eye each. Secondary procedures were removal
      and replacement, removal with subsequent laser in situ keratomileusis, and
      segment repositioning. Two risk factors for secondary surgery were identified:
      high preoperative refractive astigmatism and postoperative spherical equivalent
      greater than +/-0.5 diopter (D). The 6 eyes that had ICRS removal stabilized to
      within +/-0.25 D of the original refractive error with no surgically induced
      astigmatism within 1 to 7 weeks (mean 4 weeks) and had a final UCVA of 20/20 or
      better. In the 15 eyes that had ICRS exchange procedures, the UCVA improved by at
      least 1 line and median UCVA improved from 20/40 to 20/20. CONCLUSION:
      Preliminary data from this study indicate that removal of segments resulted in
      reversal of the refractive effect.

PMID- 11955911
TI  - Predictability and outcomes of photoastigmatic keratectomy using the Nidek EC
      5000 excimer laser.
AB  - PURPOSE: To evaluate the effect of astigmatic correction on the accuracy of the
      myopic and astigmatic correction in patients having photorefractive astigmatic
      keratectomy (PARK) and in those having photorefractive keratectomy (PRK).
      SETTING: Specialist excimer laser refractive clinic. METHODS: This prospective
      consecutive case series comprised 6097 eyes with a preoperative mean spherical
      equivalent (MSE) of -4.63 diopters (D) +/- 1.95 (SD) (range -0.75 to -13.00 D)
      and a mean cylinder of -1.13 +/- 0.73 D (range -0.50 to -6.00 D) having PARK with
      a Nidek EC-5000 excimer laser. Visual and refractive outcomes were assessed 12
      months postoperatively and compared with those in 3004 eyes that had spherical
      PRK. RESULTS: At 12 months, the MSE was -0.02 +/- 0.79 D and the mean cylinder
      was -0.49 +/- 0.47 D in the PARK group; the MSE was -0.07 +/- 0.66 D in the PRK
      group. An MSE within +/-0.05 D of emmetropia was achieved by 69.8% and within +/
      1.00 D, by 87.9%. The uncorrected visual acuity (UCVA) was 20/20 or better in
      42.6% and 20/40 or better in 91.2%. Statistical significance (P <.001, analysis
      of variance) was achieved for MSE, sphere, cylinder, haze, and visual acuity
      (best corrected [BCVA] and UCVA) based on the preoperative cylinder. The loss of
      BCVA varied from 1.1% to 5.8% depending on the degree of astigmatism treated.
      Accuracy varied with the attempted myopic correction and the attempted astigmatic
      correction. CONCLUSIONS: Excimer laser PARK was an effective treatment for
      compound myopic astigmatism, but predictability decreased and complications
      increased as the attempted astigmatic correction increased.

PMID- 11955912
TI  - Selective argon laser suturelysis versus needle suturelysis to treat induced
      corneal astigmatism after cataract surgery.
AB  - PURPOSE: To compare the complications and subjective experience of patients
      having argon laser suturelysis (LS) with those of patients having needle
      suturelysis (NS) for corneal astigmatism after extracapsular cataract extraction
      (ECCE). SETTING: Department of Ophthalmology, Tan Tock Seng Hospital, Singapore.
      METHODS: This prospective study comprised 30 patients (30 eyes) with more than
      3.00 diopters of with-the-rule astigmatism after ECCE. A minimum of 5 weeks after
      surgery, 2 sutures along the steepest meridian were lysed by the same surgeon, 1
      by a needle and the other by laser using a Hoskins lens. Patients were randomized
      to receive NS first followed by LS or LS followed by NS. The complications were
      recorded. The patients subjectively graded their fear and discomfort/pain during
      suturelysis using a scale from 0 to 10. Patient preference for either procedure
      was also recorded. RESULTS: The complications of NS were conjunctival epithelial
      defect (17/30), subconjunctival hemorrhage (13/30), and corneal abrasion (4/30)
      and of LS, minor conjunctival burn (1/30) and conjunctival epithelial defect
      (1/30). The mean subjective fear and discomfort/pain scores in the NS group were
      significantly higher than in the LS group (P =.0010 and P =.0014, respectively).
      Nineteen patients preferred LS, 3 preferred NS, and 8 had no preference for
      either procedure. CONCLUSION: Argon laser suturelysis was associated with fewer
      complications than NS and was preferred by patients.

PMID- 11955913
TI  - Alkalinization increases penetration of lidocaine across the human cornea.
AB  - PURPOSE: To test the hypothesis that corneal permeability of lidocaine complies
      with the principle of nonionic diffusion. SETTING: Department of Ophthalmology
      and Institute of Pharmacology, Vienna, Austria. METHODS: Human corneas, mounted
      in an in vitro perfusion system under short-circuit conditions, were exposed on
      the epithelial (tear) side to lidocaine 4% in a buffered solution of pH 5 or pH
      7. The endothelial bathing solutions had a constant pH of 7.4. Both solutions
      were adjusted to an osmolarity of 290 mOsm/L. The lidocaine permeability of the
      isolated corneas was assessed from the fluxes of 14C-labeled lidocaine across the
      tissue, measured at 15-minute intervals for 180 minutes, and corrected for the
      unidirectional fluxes of 3H-polyethylene glycol, a marker for the extracellular
      pathway. The corneal tissue content of lidocaine was estimated from the time span
      until the unidirectional lidocaine fluxes across the cornea reached a steady
      state. RESULTS: The mean transcorneal fluxes of lidocaine in the steady state (90
      to 180 minutes) were 72% higher at pH 7 than at pH 5 (101 mmol/min +/- 37 (SD)
      versus 59 +/- 34 nmol/min.cornea; P <.002). The corneal content of lidocaine in
      the steady state was 65% higher at pH 7 than at pH 5 (2.8 +/- 0.9 micromol/cornea
      versus 1.7 +/- 1.2 micromol/cornea; not significant). CONCLUSIONS: A shift in
      solution pH from 5 to 7 significantly increased the corneal permeability of
      topically applied lidocaine. Alkaline pH-adjustment of topical lidocaine
      solutions is easy to perform by adding sodium bicarbonate. The main clinical
      advantages of anesthetic solutions buffered at pH 7 are increased penetration
      rates, effectiveness, prolonged action time, and a reduction in local irritation
      and lacrimation.

PMID- 11955914
TI  - Downregulated expression of ADAM9 in anterior polar cataracts.
AB  - PURPOSE: To determine whether ADAM (a disintegrin and metalloproteinase) is
      regulated in lens epithelial cells (LECs) of patients with anterior polar
      cataracts and by transforming growth factor (TGF)-beta 1 in cultured LECs.
      SETTING: Department of Ophthalmology and Visual Science, College of Medicine, The
      Catholic University of Korea, Seoul, Korea. METHODS: Lens epithelial cells
      attached to the anterior capsules of human cataractous lenses with nuclear and
      anterior subcapsular cataracts and noncataractous lenses were analyzed by reverse
      transcribed-polymerase chain reaction for the expression of ADAMs. The effect of
      TGF-beta 1 on ADAM gene expression was also tested in mouse lens epithelial
      explants and cultured LEC lines (alpha TN-4 and HLE B-3). RESULTS: Significantly
      reduced expression of mRNA for ADAM9 was observed in LECs from patients with
      anterior polar cataracts. The expression of mRNA for ADAM9 was downregulated by
      TGF-beta 1 in cultured human LECs. Treatment of cultured mouse LECs with TGF-beta
      1 led to a reduction in ADAM1 mRNA. CONCLUSIONS: ADAMs are expressed and
      regulated in LECs. The downregulated expression of ADAM9 may serve as a marker
      for anterior polar cataracts in addition to previously known proteins,
      fibronectin, alpha-SMA, and beta ig-h3. The functions of this protein in lens
      pathology require further investigation.

PMID- 11955915
TI  - Effect of vancomycin on Staphylococcus epidermidis adherence to poly(methyl
      methacrylate) intraocular lenses.
AB  - PURPOSE: To study the adherence of Staphylococcus epidermidis in variable loads
      (10(8) cfu/mL and 10(3) cfu/mL) to poly(methyl methacrylate) (PMMA) intraocular
      lenses (IOLs) and to evaluate the effect of vancomycin treatment on S epidermidis
      adherence to the IOL. SETTING: L.V. Prasad Eye Institute, Hyderabad, India.
      METHODS: The study was designed in 2 parts. Phase I: Twelve PMMA IOLs were soaked
      in a solution of S epidermidis, randomized to 10(8) cfu/mL or 10(3) cfu/mL. They
      were rinsed or rinsed and vortexed and cultured. Phase II: Twelve IOLs were
      treated with vancomycin (10 mg/mL), randomized to before and after treatment with
      S epidermidis. RESULTS: Staphylococcus epidermidis adhered to all portions of the
      IOL with 10(8) cfu/mL and 10(3) cfu/mL bacterial loads. Treatment with vancomycin
      reduced S epidermidis adherence. CONCLUSION: Pretreatment of an IOL with
      vancomycin or a suitable antibiotic agent appears to reduce bacterial adherence
      to the IOL. Placement of a sustained-release device that could release an
      antibiotic agent over a specific period, reducing the incidence of postcataract
      endophthalmitis, should be studied.

PMID- 11955916
TI  - Bilateral acute postoperative retinal detachment after cataract extraction: case
      report and review of the literature.
AB  - A 57-year-old white man had extracapsular cataract extraction complicated by
      vitreous loss. On postoperative day 1, he was noted to have a total retinal
      detachment (RD) with vitreous hemorrhage. No predisposing anatomic risk factors
      were present except for the vitreous loss. During the RD repair, 2 small superior
      tears were discovered. Eleven months later, the patient had uneventful
      phacoemulsification in the fellow eye. On postoperative day 1, he again had a
      total RD with a superior retinal tear. Meticulous retinal evaluation had been
      performed preoperatively, and no holes or tears were discovered. The RD was
      repaired, and the best corrected visual acuity at the last examination was 20/40
      in both eyes.

PMID- 11955917
TI  - Stabilization of flat anterior chamber after trabeculectomy with Healon5.
AB  - A 64-year-old phakic patient had a trabeculectomy complicated by complete
      shallowing of the anterior chamber 10 days postoperatively. Despite repair of a
      conjunctival wound dehiscence and reformation of the anterior chamber with sodium
      hyaluronate 3.0%-chondroitin sulfate 4.0% (Viscoat), he had a flat anterior
      chamber again the following day with 360 degrees of pupillary synechias and lens
      to-cornea touch. Sodium hyaluronate 2.3% (Healon5) instilled through a
      paracentesis at the slitlamp lysed the synechias, stabilized the anterior
      chamber, facilitated filtration, and prevented complications from hypotony. The
      unique properties of Healon5 allowed for a conservative and less invasive
      approach in the management of this particular complication.

PMID- 11955918
TI  - Posttraumatic neovascularization in a cataractous crystalline lens.
AB  - A 73-year-old woman presented with a dense traumatic cataract and intralens
      angiogenesis. Slitlamp examination showed abundant blood vessels in the lens
      stroma. Microscopic examination confirmed the presence of blood cells in the
      lumen. The angiogenesis represented an ingrowth into the lens from posterior
      synechias. Pathologic angiogenesis is frequently seen in the retina, vitreous,
      iris, and cornea but is rarely seen in the crystalline lens. This is the first
      well-documented case of angiogenesis in the lens stroma.

PMID- 11955919
TI  - Complete anterior capsule contraction after phacoemulsification with acrylic
      intraocular lens and endocapsular ring implantation.
AB  - A 69-year-old man with pseudoexfoliation syndrome and bilateral cataract had
      phacoemulsification with continuous curvilinear capsulorhexis and implantation of
      a morcher endocapsular ring and AcrySof acrylic intraocular lens (IOL) (Alcon).
      Two months later, the patient had vision loss in the left eye with a visual
      acuity of 20/500. He presented with anterior capsule fibrosis in both eyes, with
      complete occlusion of the capsule opening in the left eye and mild occlusion in
      the right eye. After a neodymium:YAG laser anterior capsulotomy in the left eye,
      visual acuity was 20/20. This case shows that endocapsular ring implantation does
      not prevent anterior capsule contraction syndrome but can prevent IOL
      decentration.

PMID- 11955920
TI  - Bilateral infectious keratitis after a laser in situ keratomileusis enhancement
      procedure.
AB  - We report a case of bilateral infectious keratitis occurring as a complication of
      bilateral simultaneous laser in situ keratomileusis enhancement procedures.
      Corneal scraping from the interface of both eyes grew Staphylococcus aureus. The
      infection cleared after treatment with fortified cefazolin, fortified gentamicin,
      and ciprofloxacin eyedrops. The patient was left with bilateral paracentral
      corneal scars. When bilateral surgery is performed, bilateral infection may occur
      as a rare complication.

PMID- 11955921
TI  - Methicillin-resistant Staphylococcus aureus keratitis after excimer laser
      photorefractive keratectomy1.
AB  - A 43-year-old woman in good health was admitted to the hospital 3 days after
      photorefractive keratectomy (PRK) in the left eye with postoperative bandage
      contact lens application. She had developed a severe keratitis with ulceration
      and hypopyon. Upon the patient's admission to the hospital, the contact lens was
      removed. Ofloxacin eyedrops were prescribed 4 times a day. In the hospital, the
      patient was successfully treated with immediate thermocautery application,
      followed by full-thickness keratoplasty the next day and intensive systemic and
      topical antibiotics. Cultures were positive for methicillin-resistant
      Staphylococcus aureus (MRSA). Severe MRSA keratitis is a rare cause of infection
      after PRK.

PMID- 11955922
TI  - Reactivation of presumed adenoviral keratitis after laser in situ keratomileusis.
AB  - We report a patient with reactivation of presumed adenoviral keratoconjunctivitis
      after laser in situ keratomileusis (LASIK) to correct high myopia. The
      preoperative refraction was -13.00 diopters (D) in the right eye and -14.00 D in
      the left eye, and the best corrected visual acuity was 20/20 in both eyes. On the
      first postoperative day, mild conjunctival hyperemia and multiple subepithelial
      infiltrations localized in the flap zone consistent with adenoviral
      keratoconjunctivitis were seen. After prompt treatment, the lesions resolved. As
      a consequence, LASIK successfully corrected the high myopia. Adenoviral
      keratoconjunctivitis can be reactivated after LASIK, unlike after photorefractive
      keratectomy, despite the absence of symptomatic and clinical findings before the
      procedure.

PMID- 11955923
TI  - Pyridoxine-dependent seizures: findings from recent studies pose new questions.
AB  - Pyridoxine-dependent seizures, although a rare clinical entity, have been
      recognized as an etiology of intractable seizures in neonates and infants for
      more than 45 years. Recent research has focused on the molecular and
      neurochemical aspects of this disorder, as well as the optimal treatment of the
      condition. This review discusses the clinical features and management of patients
      with pyridoxine-dependent seizures together with a new hypothesis suggesting that
      an abnormality of pyridoxine transport may underlie the pathophysiology of this
      autosomal-recessive disorder.

PMID- 11955924
TI  - Neuropsychologic and motor function in small-for-gestation preschoolers.
AB  - The aim of this study was to evaluate neuropsychologic and motor performance in
      term small-for-gestation preschool children. A patient-based sample of 311 5-year
      old children with birth weights less than the fifteenth percentile for gestation
      was compared with a random sample of 321 appropriate-for-gestation control
      subjects. The main assessment tools were subscales from the Wechsler Preschool
      and Primary Scale of Intelligence Revised, subscales from the Illinois Test of
      Psycholinguistic Abilities, tests of manual dexterity and figure copying, and the
      Peabody Developmental Motor Scales. The small-for-gestation children had mean
      scores on tests of visuospatial and visuomotor abilities that were one fourth
      standard deviation lower than appropriate-for-gestation control subjects and
      slightly lower scores on manual dexterity. The small-for-gestation children were
      comparable to appropriate-for-gestation children regarding motor performance. We
      therefore conclude that the neuropsychologic and neuromotor performance in
      preschool years of term small-for-gestation children is reassuring.

PMID- 11955925
TI  - Increased frequency of interleukin-1beta (-511) allele 2 in febrile seizures.
AB  - Febrile seizures can be the first sign of epilepsy. In a recent study, patients
      with temporal lobe epilepsy were reported to carry the interleukin-1beta allele 2
      at position -511 more often than healthy control subjects. Because pro
      inflammatory cytokines, such as interleukin-1, are well-known inducers of fever
      and therefore could play an important part in the pathogenesis of febrile
      seizures, we have, in this study, analyzed the cytokine gene polymorphism of
      interleukin-1beta at position -511 in children with febrile seizures and control
      subjects. We found a statistically significant increase in the frequency and the
      carriage of interleukin-1beta (-511) allele 2 in children with febrile seizures
      (n = 35) compared with healthy blood donors (n = 400) (P = 0.03 and P = 0.05,
      respectively). In previous studies, this allele has been connected to increased
      in vitro production of interleukin-1. Children with febrile seizures may
      therefore have an increased pro-inflammatory reaction during fever. This pro
      inflammatory reaction may also predispose some children to the development of
      epilepsy.

PMID- 11955926
TI  - Three novel SURF-1 mutations in Japanese patients with Leigh syndrome.
AB  - Leigh syndrome, a severe neurodegenerative disorder, commonly is associated with
      cytochrome c oxidase deficiency. Recent studies in white patients indicate that
      SURF-1 gene mutations can cause Leigh syndrome associated with cytochrome c
      oxidase deficiency. When we measured cytochrome c oxidase activity in cultured
      lymphoblastoid cells from our Japanese patients with typical Leigh syndrome,
      three patients demonstrated cytochrome c oxidase deficiency. Three novel
      mutations of the SURF-1 gene were identified in two of these three patients with
      cytochrome c oxidase deficiency. All mutations predicted loss of function of the
      SURF-1 protein; in both patients' cells, cytochrome c oxidase activity was
      decreased to less than 20% of the control mean. These results indicate that
      cultured lymphoblastoid cells are useful for elucidating the etiology of Leigh
      syndrome, and that loss of function of the SURF-1 gene product can be responsible
      for Leigh syndrome associated with severe cytochrome c oxidase deficiency in
      Japanese patients.

PMID- 11955927
TI  - Tandem mass spectrometry and newborn screening: pilot data and review.
AB  - United States legislatures are debating whether to use tandem mass spectrometry
      to expand the roster of inherited disorders tested in newborn screening programs.
      The debate is hampered because published financial data comparing charges
      associated with late vs early diagnosis are not readily available. We provide
      pilot financial data comparing late diagnosis vs presumptive diagnosis and early
      management taken from consecutive patients with propionic acidemia diagnosed from
      1995-1998 in New Hampshire. We extrapolated from these data and the incidence of
      treatable inborn errors of metabolism to estimate the projected yearly savings of
      critical care charges if expanded newborn screening were instituted. We conclude
      that institution of expanded screening will bring diminished morbidity and large
      savings in yearly chronic care and critical care charges.

PMID- 11955929
TI  - Decrease in neuron size in docosahexaenoic acid-deficient brain.
AB  - Docosahexaenoic acid is an important fatty acid for neuronal function because its
      deficiency leads to many behavioral and functional deficits. In a previous study,
      we reported that docosahexaenoic acid deficiency caused a reduction in the size
      of neurons of the CA1 region in the hippocampus. To extend these results to other
      regions of the brain, the present study entailed a morphologic analysis of
      neuronal size in hippocampus, hypothalamus, piriform cortex, and parietal cortex
      in rats that were raised on docosahexaenoic acid-deficient and supplemented diets
      for three generations. Neuron size in these regions was measured both at weaning
      (21 days) and maturity (68 days), and docosahexaenoic acid content in the brain
      was measured on a separate set of sibling rats using fatty acid analysis. Neuron
      size in hippocampus, hypothalamus, and parietal cortex decreased in weanling and
      in piriform cortex in mature rats raised on the docosahexaenoic acid-deficient
      diet. The brains of these rats exhibited a nearly 90% decrease of docosahexaenoic
      acid. Decrease of neuron size has been linked to a loss of optimal function in
      neurons. In the United States, human infant-milk formulas use vegetable oils as
      fat sources that lack docosahexaenoic acid. If docosahexaenoic acid deficiency
      reduces neuron size, then human infants raised on these formulas may also have
      smaller neurons relative to breast-fed infants.

PMID- 11955928
TI  - Magnetic resonance spectroscopy and analysis of MECP2 in Rett syndrome.
AB  - We studied the in vivo cerebral metabolites and documented the presence of MECP2
      gene mutations in six Chinese females with Rett syndrome. Magnetic resonance
      spectroscopy spectra from the frontal lobe (gray and white matter) and deep gray
      nuclei (basal ganglia and thalamus) of either side were obtained. N
      acetylaspartate/total creatine, choline/total creatine, and N
      acetylaspartate/choline ratios were analyzed and compared with six healthy age
      matched female control subjects. MECP2 gene mutation was identified in four
      patients; one patient had polymorphism and one patient did not have gene
      mutation. N-acetylaspartate/total creatine of the frontal lobe of all patients
      (mean: 2.63, S.D. = 0.33) was decreased compared with age-matched control
      subjects (mean: 3.15, S.D. = 0.27), and the difference was statistically
      significant (P = 0.017) with a mean difference of 0.52 (95% CI = 0.68-0.36). The
      difference in all other metabolite ratios in the frontal lobe and deep gray
      nuclei were not statistically significant compared with age-matched control
      subjects. Mild frontal lobe and anterior temporal lobe atrophy was present in
      three patients. Proton-magnetic resonance spectroscopy is a sensitive method
      capable of detecting the biochemical changes in Rett syndrome and is able to
      detect changes before conventional magnetic resonance imaging. Our preliminary
      results suggest that reduction in N-acetylaspartate/total creatine ratio may not
      be related to the MECP2 mutation.

PMID- 11955930
TI  - Hematogenous brain metastasis in children.
AB  - Hematogenous brain metastases are uncommon in childhood. Three patients and a
      literature review that includes centers reporting up to 36 years of experience
      are presented in this study. The total of 2,040 patients includes our three
      examples of one neuroblastoma, one hepatoblastoma, and one adrenal carcinoma.
      Cerebral hematogenous metastases were reported in 4.4% of 429 patients with
      neuroblastoma, 1.9% of 574 rhabdomyosarcoma patients, 6.5% of 386 patients with
      osteosarcoma, 3.3% of 487 Ewing sarcoma patients, 3.6% of 44 melanoma patients,
      13.5% of 37 patients with germ cell tumors, and 1.3% of the 78 patients with
      Wilms tumor. Five miscellaneous patients included three with a hepatoblastoma and
      one each with adrenal carcinoma and nephroma. All of the large series reports
      have been published in oncology journals.

PMID- 11955931
TI  - Oral high-dose phenobarbital therapy for early infantile epileptic
      encephalopathy.
AB  - We report oral high-dose phenobarbital therapy for a patient with early infantile
      epileptic encephalopathy with suppression bursts (Ohtahara syndrome). At 1 month
      of age, many series of tonic spasms, with raising limbs and crying lasting for a
      few minutes, developed and increased up to approximately 300 times per day.
      Initially intravenous midazolam (0.5 mg/kg/hour) slightly decreased the seizures,
      although oral vitamin B6, valproic acid, clonazepam, and zonisamide had little
      effect. Oral high-dose phenobarbital therapy was begun at a dosage of 15
      mg/kg/day, and the seizures markedly decreased to 5-10 times per day and the
      epileptic discharges on electroencephalogram greatly decreased. Serum
      phenobarbital levels ranged between 60 and 100 mg/dL. High-dose phenobarbital
      therapy should be considered for the treatment of early infantile epileptic
      encephalopathy with suppression bursts.

PMID- 11955932
TI  - Pseudotumor cerebri manifesting as stiff neck and torticollis.
AB  - Stiff neck and torticollis are significant signs of neurologic disease. Nuchal
      rigidity is often associated with meningitis, subarachnoid hemorrhage, and
      posterior fossa tumor. Torticollis may be encountered in inflammatory disorders,
      such as cervical lymphadenitis, or it can be a sign of spinal cord syrinx or of
      central nervous system neoplasm. We report on three prepubertal children in whom
      stiff neck and torticollis were the presenting signs of pseudotumor cerebri. In
      all, the removal of 6-7 mL of cerebrospinal fluid led to prompt relief of
      symptoms and signs. We suggest that in the presence of unexplained stiff neck or
      torticollis in children, the optic discs should be examined to exclude
      pseudotumor cerebri.

PMID- 11955933
TI  - Benign intracranial hypertension: atypical presentation of Miller Fisher
      syndrome?
AB  - Acute ocular paresis, nausea, vomiting, and headaches associated with high
      intracranial pressure without obvious intracranial pathology are typical features
      of benign intracranial hypertension. We describe two young children whose
      presentation, initially suggestive of idiopathic or benign intracranial
      hypertension, evolved to comprise ophthalmoplegia, ataxia, and areflexia. This
      triad characterizes Miller Fisher syndrome, a clinical variant of Guillain-Barre
      syndrome that occurs rarely among children. In both patients, this diagnosis was
      supported by the clinical course and neurophysiologic findings. Plasma serology
      was positive for Campylobacter jejuni and anti-GQ1b antibodies in one patient and
      for antimyelin antibodies in the other. This report of two children with Miller
      Fisher syndrome presenting with intracranial hypertension adds to the findings
      for a similar patient treated previously, which raises the question concerning
      the possible role or contribution of benign intracranial hypertension in Miller
      Fisher syndrome.

PMID- 11955934
TI  - Human immunodeficiency virus-1 infection and multiple sclerosis-like illness in a
      child.
AB  - We present a child with human immune deficiency virus-1 infection associated with
      a multiple sclerosis-like illness. This case is the first reported of human
      immune deficiency virus-1 infection and a disease indistinguishable from multiple
      sclerosis in a child. Because of the rarity of either disease in pediatric
      patients, their coexistence in a child argues in favor of a casual association
      between the two illnesses, thus reinforcing the long-held assumption that viral
      agents may trigger some of the immunologic abnormalities underlying multiple
      sclerosis. Cases in which such an association was present in adults are also
      described in this article.

PMID- 11955935
TI  - Paradoxical eyelid movement in trisomy 2p.
AB  - Paradoxical eyelid movement was reported in a 12-year-old female with
      46,XX,dup(2)(p25.3p22.2). Alternating seesaw-like movement of the eyelids during
      lateral gazing had been observed at 5 months of age when she was first referred
      to our neuropediatric outpatient department, and the abnormal lid movement
      persisted without any change for 11 years. The differentiation of the features of
      the paradoxical lid movements in our patient from those of Duane syndrome were
      discussed, and a possible pathogenesis is discussed as well. Besides
      ophthalmologic abnormalities, the patient demonstrated severe psychomotor
      retardation, marked growth failure, symptomatic generalized epilepsy, and
      multiple anomalies. The dysmorphism consisted of a cleft lip, a narrow high
      arched palate, malalignment, lowset ears, and kyphoscoliosis caused by fused
      thoracic vertebrae.

PMID- 11955936
TI  - Mitochondrial DNA depletion in Leigh syndrome.
AB  - Leigh syndrome is a heterogenous neurologic disease characterized by seizures,
      developmental delay, muscle weakness, respiratory abnormalities, optic
      abnormalities, including atrophy and ophthalmoplegia, and progressive cranial
      nerve degeneration with early onset in infants and children. Diagnosis can be
      confirmed by characteristic pathologic findings of necrosis in the basal ganglia,
      thalamus, and brainstem. Severe dysfunction of mitochondrial energy metabolism is
      generally present and involved in the etiology of this degenerative central
      nervous system disease. At the molecular level, a number of point mutations have
      been located in mitochondrial DNA genes, including ATPase6 and tRNA(Lys) genes,
      and in nuclear genes encoding subunits of oxidative enzymes, such as pyruvate
      dehydrogenase. Biochemically these mutations are responsible for enzymatic
      defects in either respiratory complexes (I, IV, or V) or pyruvate dehydrogenase.
      We describe here the first case of Leigh syndrome with marked depletion of
      mitochondrial DNA levels in skeletal muscle and abnormal activities in skeletal
      muscle of mitochondrial respiratory complexes I, III, IV, and V.

PMID- 11955939
TI  - Oral motor dysfunction in nephropathic cystinosis.

PMID- 11955940
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on serum inhibin
      concentrations and inhibin immunostaining during follicular development in female
      Sprague-Dawley rats.
AB  - Intact and hypophysectomized immature rats were pretreated with 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD; 0 or 32 microg/kg p.o.) and sacrificed
      throughout synchronized follicular development (0, 12, 24, 48, and 72 h after
      equine chorionic gonadotropin, eCG). TCDD administration to intact rats resulted
      in a premature elevation of serum FSH and LH by 12 h post-eCG. In intact rats
      pretreated with TCDD, the intensity of ovarian immunoreactivity for inhibin and
      the number of ovarian follicles staining for inhibin in midsaggital ovarian
      sections were decreased at the time of eCG administration (24 h post-TCDD) in
      comparison to controls. However, this decreased ovarian staining for inhibin was
      not associated with alterations in serum inhibin concentrations. Serum inhibin
      was suppressed in TCDD-treated rats when compared to intact controls only at 24 h
      post-eCG. Hypophysectomized animals exhibited no effect of TCDD on serum inhibin
      at any timepoint but did have decreased estradiol concentrations during
      follicular development. In summary, TCDD reduced serum concentrations of inhibin
      after the premature increases in FSH and LH suggesting that inhibin is not
      important in the initial elevation of FSH following exposure to TCDD.

PMID- 11955942
TI  - Low dose effect of in utero exposure to bisphenol A and diethylstilbestrol on
      female mouse reproduction.
AB  - In utero exposure to bisphenol-A (BPA) at doses relevant to human consumption has
      been reported to accelerate weight gain and puberty in female mice, but the
      effect of low dose BPA on female reproduction has not been described. In this
      study, we investigated low dose effects of BPA on sexual maturation and
      reproduction in female ICR/Jcl mice. Pregnant ICR mice (F0) were injected (s.c.)
      with BPA (2 and 20 microg/kg), diethylstilbestrol (DES; 0.02, 0.2, and 2
      microg/kg) or oil vehicle once per day from gestational days 11-17. For both
      female and male offspring (F1), body weights were measured on postnatal day (PND)
      0 (the day of birth), 11, 22, and 60, and anogenital distance (AGD) was measured
      on PNDs 22 and 60. Pups were weaned at PND 22 and males were caged separately
      from females. Vaginal smears were taken daily beginning the day of vaginal
      opening for 30 days. The age at vaginal opening was significantly earlier in all
      exposed females except for 2 microg/kg BPA females compared to oil controls. Body
      weight at vaginal opening was lower than controls in all exposed females. The
      first vaginal estrus was earlier in all exposed females except for the 2
      microg/kg BPA group females compared to controls. From PND 90 to 120,
      gestationally exposed F1 female mice were mated with unexposed males. Total
      numbers of pups and sex ratio in F1 mice exposed to BPA or DES, and those of
      their offspring (F2) were not different from controls in any treatment group. The
      present results indicate that prenatal exposure to low doses of BPA and DES
      induces early vaginal opening, but does not affect reproductive functioning at
      the first breeding.

PMID- 11955941
TI  - Developmental effects of perinatal exposure to bisphenol-A and diethylstilbestrol
      on reproductive organs in female mice.
AB  - Reproductive tract development is influenced by estrogen. The aim of this study
      was to determine the effects of an environmental estrogenic chemical bisphenol-A
      (BPA) on prenatal and postnatal development of female mouse reproductive organs.
      In the prenatal treatment group, BPA or the synthetic estrogen diethylstilbestrol
      (DES) were given by subcutaneous (s.c.) injections to pregnant mice during
      gestational days 10-18. Some offspring treated prenatally with 10 and 100 mg/kg
      bw BPA or 0.67 and 67 microg/kg bw DES were ovariectomized at 30 days and
      sacrificed at 40 days of age. Vaginal smears were examined in the remaining
      offspring, then these offspring were mated with normal males. Prenatal exposure
      to 10 mg/kg BPA reduced the number of mice with corpora lutea compared to sesame
      oil controls at 30 days, but more than 80% of mice from either prenatally exposed
      BPA group were fertile at 90 days. Mice exposed prenatally to maternal doses of
      67 microg/kg DES were sterile and showed ovary-independent vaginal and uterine
      epithelial stratification; however, mice exposed prenatally to BPA did not show
      ovary-independent vaginal and uterine changes. The number of offspring and litter
      sex ratio from mice exposed prenatally to BPA (10 or 100 mg/kg) or 0.67 microg/kg
      DES were not different compared to controls. In postnatal treatment group, female
      mice were given s.c. injections of BPA (15 or 150 microg/pup) or DES (0.3 or 3
      microg/pup) for 5 days from the day of birth, then some mice were ovariectomized
      at 30 days and examined at 40 and 90 days. In the remaining mice, vaginal smears
      were examined from 61 to 90 days and ovarian histology was evaluated at 90 days.
      Mice exposed postnatally to 150 microg BPA exhibited ovary-independent vaginal
      epithelial stratification. Postnatal DES (0.3 and 3 microg) treatment also
      induced ovary-independent vaginal stratification. Polyovular follicles having
      more than one oocyte in a follicle were induced by postnatal injections of BPA
      (150 microg) or DES (0.3 or 3 microg) at 30 days. These findings indicate for the
      first time that a large dose of BPA can induce ovary-independent vaginal
      epithelial changes when given postnatally but not prenatally.

PMID- 11955943
TI  - Low-dose bisphenol A does not affect reproductive organs in estrogen-sensitive
      C57BL/6N mice exposed at the sexually mature, juvenile, or embryonic stage.
AB  - Bisphenol A (BPA) is used on a large scale in the manufacture of polycarbonate
      plastics. BPA has been shown to bind weakly to both estrogen receptor (ER) alpha
      and ER beta. The objective of this study was to evaluate the effects of low-dose
      BPA on male sexual development after exposure at various stages of development.
      Mice of the estrogen-sensitive strain C57BL/6N were exposed to BPA orally at
      doses of 2, 20, or 200 microg/kg at various stages, i.e. adulthood, the immature
      stage just after weaning, or the embryonic/fetal stage, to evaluate the effects
      of low-dose BPA on male reproductive organs. Body weight changes, weights of
      reproductive organs (testes, epididymides, seminal vesicles), cauda epididymal
      sperm density, and histology of reproductive organs including the ventral
      prostate were not affected by exposure to BPA at any dose examined. The results
      of this study indicate that exposure of estrogen-sensitive C57BL/6N mice to low
      dose BPA did not reduce sperm density or disrupt development of the male
      reproductive organs.

PMID- 11955944
TI  - Effects of in utero linuron exposure on rat Wolffian duct development.
AB  - Linuron is an herbicide that displays weak androgen receptor antagonist activity.
      Male offspring exposed in utero to 50 mg/kg/day linuron often exhibit
      malformations in Wolffian duct derivatives (i.e. the epididymis and vas
      deferens). The objectives of this study were to determine the point during the
      perinatal period that linuron-induced epididymal lesions can be identified, to
      characterize linuron-mediated perinatal testicular and epididymal pathology, and
      to determine whether male rat fetuses exposed prenatally to linuron exhibit
      decreased intratesticular and serum testosterone (T) levels. Pregnant rats were
      administered corn oil vehicle or linuron by gavage at 0 or 50 mg/kg/day (n = 3
      controls, 5-11 linuron-treated dams per time point) from gestation days (GD) 12
      to 21 or to termination. Male fetuses or offspring were necropsied on GD 17, 19,
      and 21, and postnatal days (PND) 7 and 14. Epididymal malformations were not
      observed in fetuses from linuron-treated dams but were seen in linuron-exposed
      male offspring on PND 7 and 14. No testicular lesions were observed at any time
      point. The growth and development of linuron-exposed fetuses were altered, as
      evidenced by slight decreases in fetal weight and increased levels of
      immunoreactive proliferating cell nuclear antigen (PCNA) on GD 21.
      Intratesticular and serum T levels were not decreased in linuron-exposed male
      fetuses. These findings indicate that the adversely altered adult phenotype
      following in utero exposure to linuron is very similar to that produced by the
      antiandrogens di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP).
      However, the absence of testicular lesions or alterations in fetal testosterone
      levels would suggest that the effect of linuron on the developing Wolffian ducts
      is distinctly different from DBP or DEHP.

PMID- 11955945
TI  - Changes in vascular dynamics of the adult rat testis leading to transient
      accumulation of seminiferous tubule fluid after administration of a novel 5
      hydroxytryptamine (5-HT) agonist.
AB  - The aim of the present study was to evaluate the possible mechanisms of
      testicular toxicity of GR40370X, a follow-up 5-hydroxytryptamine (5-HT) receptor
      agonist. Administration to adult male rats of a single (toxic) dose of 750 mg/kg
      GR40370X induced marked distension of seminiferous tubules and an associated
      increase in testis weight at 12-24 h with a gradual recovery to normal by 96 h.
      Seminiferous tubule distension was due to expansion of the lumen, which occurred
      at all stages of the spermatogenic cycle and was accompanied by vacuolation of
      the cytoplasm of elongating spermatids. Seminiferous tubule distension was
      preceded/accompanied by distension of the efferent ducts and rete testis with
      maximal changes evident at 24-48 h. These changes could not be explained by
      increases in seminiferous tubule fluid or interstitial fluid production, as both
      were reduced (15-20%), rather than increased, by treatment. Examination of the
      vasculature after treatment with 750 mg/kg GR40370X revealed significant changes
      that were maximal at 4 h and thus preceded rete/testicular changes. Veins of the
      mediastinal venous plexus, which overlies the rete, were constricted and
      arteriovenous anastomoses in the spermatic cord were shut/constricted, as
      determined (indirectly) by measurement of the dilution of outflowing testicular
      venous blood by incoming arterial blood. The latter effect of GR40370X could be
      blocked by co-administration of minoxidil, a vasodilator. Vascular effects of
      GR40370X had normalised by 24-48 h. It was also noted that administration of a
      toxic dose of GR40370X significantly lowered blood levels of LH and testosterone,
      though these changes were considered to be incidental and not involved in the
      other changes described above. None of the above changes were induced by a
      pharmacologically active dose (1 mg/kg) of GR40370X. It is concluded that the
      mechanism of testicular toxicity induced by 750 mg/kg GR40370X results from
      primary effects on the vasculature of the testis/neighbouring region, which in
      turn lead to impaired fluid resorption from the efferent ducts and rete and
      thence to accumulation of seminiferous tubule fluid in the rete and testis.

PMID- 11955946
TI  - Impairment of male rat reproductive function in F1 offspring from dams exposed to
      2-bromopropane during gestation and lactation.
AB  - The toxic effects of 2-bromopropane (2-BP) on the reproductive tracts of male F1
      offspring from dams exposed to 2-BP during gestation and lactation were
      investigated. Ten pregnant (sperm-positive) Sprague-Dawley rats per group were
      exposed sc to 2-BP at 135, 405, and 1215 mg/kg/day from gestation day (GD) 6 to
      postnatal day (PND) 20. 2-BP decreased the proportion of dams littering at the
      two highest doses. At the highest dose, the rate of delivery and surviving pups
      were significantly lower than in the controls (P < or = 0.05). The relative
      weights of testes vs. brain were significantly lower than the controls (P < or =
      0.05) on PND 33 and 63 at 405 mg/kg/day, and on PND 90 at 1215 mg/kg/day in the
      F1 rats. Seminiferous tubule atrophy, germ cell loss, and increased Leydig cell
      proliferation were observed at the highest dose by histopathologic examination.
      Female offspring has a decrease in all follicle types at the high dose. These
      results suggest that gestational and lactational exposure to 2-BP at a high
      maternally toxic dose impairs the development of the reproductive organs of the
      offspring.

PMID- 11955947
TI  - The effect of methoxychlor on the epididymal antioxidant system of adult rats.
AB  - Methoxychlor is widely used as a pesticide in many countries and has been shown
      to induce reproductive abnormalities in male rats, causing reduced fertility. The
      mechanism of action of methoxychlor on the male reproductive system is not clear.
      In the present study we investigated whether administration of methoxychlor
      induces oxidative stress in the epididymis and epididymal sperm of adult rats.
      Methoxychlor (50, 100, or 200 mg/kg body weight/day) was administered orally for
      1, 4, or 7 days. The animals were killed using anesthetic ether 24 h after of the
      last treatment. Epididymal sperm were collected by cutting the epididymis into
      small pieces in Ham's F-12 medium at 35 degrees C. The body weight and weights of
      the testis, liver, and kidney did not show any significant changes in the
      methoxychlor-treated rats. The weight of the epididymis, seminal vesicles, and
      ventral prostate as well as epididymal sperm counts decreased after 50, 100, or
      200 mg/kg/day for 7 days but remained unchanged after shorter courses of
      treatment. Epididymal sperm motility was decreased in a dose-dependent manner in
      the animals treated with methoxychlor for 4 or 7 days. The activities of the
      antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and
      glutathione peroxidase were decreased while the levels of hydrogen peroxide and
      lipid peroxidation were increased in the epididymal sperm as well as in the
      caput, corpus, and cauda epididymis after 4 or 7 days of treatment. The
      activities of superoxide dismutase decreased while the levels of lipid
      peroxidation increased in the liver but not in the kidney in all groups. Co
      administration of the antioxidant vitamin E (20 mg/kg body weight/ day) to the
      200 mg/kg/d methoxychlor-treated rats for 7 days prevented significant changes in
      the antioxidant systems in the epididymis and epididymal sperm and prevented
      alterations in sperm counts and motility. The results indicated that methoxychlor
      induces oxidative stress in the epididymis and epididymal sperm by decreasing
      antioxidant enzymes, possibly by inducing reactive oxygen species. In conclusion
      the adverse effect of methoxychlor on the male reproduction could be due to
      induction of oxidative stress.

PMID- 11955949
TI  - Of diabetic mothers and their babies.

PMID- 11955948
TI  - Role of the maternal acute phase response and tumor necrosis factor alpha in the
      developmental toxicity of lipopolysaccharide in the CD-1 mouse.
AB  - The acute phase response (APR) functions to reset metabolic homeostasis following
      infectious, toxic, or traumatic insult. TNF-alpha, a putative mediator of the
      APR, has been associated with fetal death in rodents and preterm labor and
      delivery in humans. We hypothesized that physiologic changes associated with the
      maternal APR may play a role in adverse embryo/fetal outcome. Pregnant CD-1 mice
      injected i.p. with lipopolysaccharide (LPS), a model inducer of the APR, on
      gestation day (gd) 9 showed a dose-related increase in embryo death on gd 10.
      Histology indicated placental infarct and necrosis. Maternal serum TNF-alpha
      levels, measured by ELISA following administration of 0.05 mg/kg LPS on gd 9,
      were found to increase significantly and peak within 1 to 1.5 h. Pretreatment
      with 0.01 mg/kg LPS on gd 8 ameliorated embryotoxicity of the 0.05 mg/kg LPS
      treatment on gd 9 and also eliminated the increase in serum TNF-alpha. Direct LPS
      exposure in whole embryo culture was nontoxic. These data support a maternally
      mediated mechanism of LPS embryolethality, and suggest that TNF-alpha may be an
      important mediator of this developmental toxicity.

PMID- 11955950
TI  - Natural ligands of PPARgamma: are prostaglandin J(2) derivatives really playing
      the part?
AB  - The peroxisome proliferator-activated receptor (PPAR) family was discovered from
      an orphan nuclear receptor approach, and thereafter, three subtypes were
      identified, namely PPARalpha, PPARbeta or PPARgamma and PPARgamma. The two former
      seem to regulate lipid homeostasis, whereas the latter is involved, among others,
      in glucose homeostasis and adipocyte differentiation. PPARs were
      pharmacologically characterised first using peroxisome proliferators such as
      clofibrates, which demonstrate moderate affinity (efficiency at micromolar
      concentrations) and low PPARalpha/delta versus PPARgamma specificity. Hence,
      several laboratories have started the search for potent and subtype-specific
      natural PPAR activators. In this respect, prostaglandin (PG)-related compounds
      were identified as good PPARgamma agonists with varying specificity, the most
      notable PPAR ligand being 15-deoxy-Delta12-14-PGJ2 (15d-PGJ2). Recently, an
      oxidized phosphatidylcholine was identified as a potent alternative
      (patho)physiological natural ligand of PPARgamma. In the present review, we
      discuss the different PPARgamma-dependent and -independent biological effects of
      the PG PPARgamma ligands and the concern about their low potency in molecular
      models as compared with thiazolidinediones (TZDs), a family of potent (nanomolar)
      synthetic PPARgamma ligands. Finally, the oxidized lipids are presented as a
      novel and interesting alternative for discovering potent PPARgamma activators in
      order to understand more in details the implications of PPARgamma in various
      pathophysiological conditions.

PMID- 11955951
TI  - Molecular mechanism and biological functions of c-Jun N-terminal kinase
      signalling via the c-Jun transcription factor.
AB  - The regulation of c-Jun transcriptional activity by Jun N-terminal kinase (JNK)
      has become a paradigm for understanding how mitogen-activated protein (MAP)
      kinase signalling pathways elicit specific changes in gene transcription through
      selective phosphorylation of nuclear transcription factors. Selective
      phosphorylation of c-Jun by JNK is determined by a specific docking motif in c
      Jun, the delta region, which enables JNK to associate physically with c-Jun.
      Analogous MAP kinase docking motifs have subsequently been found in several other
      transcription factors, indicating that this is a general mechanism for ensuring
      specificity of signal transduction. Genetic and biochemical studies in mice,
      flies and cultured cells have provided evidence that signals relayed by JNK
      through c-Jun regulate a range of cellular processes including cell
      proliferation, tumourigenesis, apoptosis and embryonic development. Despite these
      advances, in most cases, the genes or programs of gene expression downstream of
      JNK and c-Jun, which control these processes, have not been defined. Here, we
      review the current understanding of the molecular basis and biological
      consequences of JNK signalling via c-Jun and highlight some of the mechanistic
      issues, which remain to be resolved.

PMID- 11955952
TI  - Cloning and characterization of a novel regulator of G protein signalling in
      human platelets.
AB  - In an effort to understand the modulation of G protein-coupled receptor (GPCR)
      mediated signalling in platelets, we sought to identify which regulators of G
      protein signalling proteins (RGSs) are present in human platelets. Using
      degenerate oligonucleotides, we performed RT-PCR with human platelet and
      megakaryocytic cell line RNA. In addition to confirming the presence of several
      known RGS transcripts, we found a novel RGS domain-containing transcript in
      platelet RNA. Northern blot analysis of multiple human tissues indicates that
      this transcript is most abundantly expressed in platelets compared to other
      tissues examined. Full-length cloning of this novel RGS, which we now term RGS18,
      demonstrates that this transcript is predicted to encode a 235-amino acid protein
      that is most closely related to RGS5 (46% identity) and that has approximately 30
      40% identity to other RGS proteins. RGS18 is expressed in platelet, leukocyte,
      and megakaryocyte cell lines and binds to endogenous Galphai1, Galphai2,
      Galphai3, and Galphaq but not Galphaz, Galphas or Galpha12 in vitro.

PMID- 11955953
TI  - Sphingosine 1-phosphate dynamically regulates myosin light chain phosphatase
      activity in human endothelial cells.
AB  - Sphingosine 1-phosphate (S1P) is known to induce reorganization of the actin
      cytoskeleton through activation of the GTPase Rho. We have investigated the
      dynamic behavior of Rho/Rho kinase-regulated myosin light chain (MLC) phosphatase
      activity and MLC phosphorylation in Human Umbilical Vein Endothelial Cells
      (HUVEC) stimulated with S1P. Immediately (30-60 s) after S1P stimulation, MLC
      phosphatase activity dropped and MLC phosphorylation increased in a Rho/Rho
      kinase-dependent manner. Shortly thereafter (2 min), MLC phosphatase increased
      above baseline and MLC phosphorylation correspondingly decreased to near control
      values. At this time point, formation of actin ruffles and Rac activity assays
      indicated activation of Rac. Finally, between 5 and 15 min, MLC phosphatase
      dropped to a plateau below baseline. In parallel, MLC phosphorylation became
      constantly elevated above control values. These findings indicate that S1P is
      able to induce dynamic cycles of MLC phosphatase deactivation and activation.
      This novel feature of S1P could contribute to its chemotactic and angiogenic
      activity.

PMID- 11955954
TI  - Two tetratricopeptide repeat proteins facilitate human aryl hydrocarbon receptor
      signalling in yeast.
AB  - A human aryl hydrocarbon (Ah) receptor signalling pathway was constructed in
      yeast and used to identify regulatory proteins that may be related to those
      present in mammalian cells. The sequence similarity of human hepatitis B protein
      X-associated protein 2 (XAP2) protein to yeast Cpr7 and Cns1 proteins suggested
      that these proteins might be involved in Ah receptor signalling in this model
      system. Ah receptor signalling from a lacZ reporter gene was reduced by
      approximately 60% in cells that lacked Cpr7. In vitro interaction experiments
      indicated that a Cpr7-GST fusion protein and Ah receptor formed a complex.
      Expression of Cpr7, Cns1 and the isolated tetratricopeptide repeat (TPR) region
      of Cpr7 from plasmids restored Ah receptor signalling function in the Cpr7
      deficient strain. Thus, Cpr7 and Cns1 proteins facilitate the signalling of human
      Ah receptor expressed in yeast, perhaps in the same manner as the TPR-containing
      XAP2 protein and related chaperone proteins in mammalian cells.

PMID- 11955955
TI  - Cilostazol enhances IL-1beta-induced NO production and apoptosis in rat vascular
      smooth muscle via PKA-dependent pathway.
AB  - Interleukin-1beta (IL-1beta) stimulates nitric oxide (NO) production and induces
      apoptosis in several tissues. Cilostazol is a Type 3 phosphodiesterase inhibitor.
      We investigated whether cilostazol affects IL-1beta-induced NO production and
      apoptosis in rat vascular smooth muscle cells. Cilostazol (100 nM-10 microM)
      potentiated NO production triggered by IL-1beta. The mRNA and protein expression
      of inducible NO synthase was also upregulated by cilostazol. KT5720, an inhibitor
      of protein kinase A, and N(G)-monomethyl-L-arginine, an inhibitor of NO synthase,
      abrogated cilostazol-enhanced IL-1beta-stimulated NO production and apoptosis.
      These results shows that cilostazol potentiates IL-1beta-induced NO production
      via PKA-pathway and thereafter augments apoptosis via NO-dependent pathway.

PMID- 11955956
TI  - Role of Ca(2+) on TNF-alpha and IL-6 secretion from RBL-2H3 mast cells.
AB  - Ca2+ acts as an important second messenger in mast cells. However, the mechanisms
      involved in the secretion of inflammatory cytokines from activated mast cells are
      unknown. In this study, we examined the signaling pathway involved in calcium
      related cytokine secretion in a mast cell line, RBL-2H3 cells. We report that
      treatment with 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid
      acetoxymethyl ester (BAPTA-AM), a chelator of intracellular calcium, can inhibit
      IgE-stimulated TNF-alpha and IL-6 secretion in a concentration-dependent manner
      with IC50 values of 0.41 and 0.014 microM, respectively. Maximal inhibition of
      TNFalpha- and IL-6 secretion was 58.5 +/- 3% and 87 +/- 8% in BAPTA-AM,
      respectively. BAPTA-AM also completely inhibited the IgE-induced TNF-alpha and IL
      6 mRNA levels. In activated RBL-2H3 cells, the expression level of NF-kappaB/Rel
      A protein increased in the nucleus. However, the level of NF-kappaB/Rel A in
      nucleus was decreased by treatment of BAPTA-AM. In addition, BAPTA-AM completely
      inhibited the IgE-induced IkappaB kinase beta (IKKbeta) activation and
      IkappaBalpha phosphorylation. These observations demonstrate that the
      intracellular Ca2+ may play an important role in IgE-induced TNF-alpha and IL-6
      secretion from mast cells via IKKbeta activation.

PMID- 11955957
TI  - Protein kinase C-dependent inhibition of the lysosomal degradation of endocytosed
      proteins in rat hepatocytes.
AB  - We studied the role of protein kinase C (PKC) in the lysosomal processing of
      endocytosed proteins in isolated rat hepatocytes. We used [14C]sucrose-labeled
      horseradish peroxidase ([14C]S-HRP) to simultaneously evaluate endocytosis and
      lysosomal proteolysis. The PKC activator phorbol 12-myristate 13-acetate (PMA)
      inhibited the lysosomal degradation of [14C]S-HRP (1 microM PMA: 40% inhibition,
      P<.05), without affecting either the endocytic uptake or the delivery to
      lysosomes. However, PMA was not able to affect the lysosomal processing of the
      beta-galactosidase substrate dextran galactosyl umbelliferone. The PKC
      inhibitors, chelerytrine (Che), staurosporine (St) and Go 6976, prevented PMA
      inhibitory effect on lysosomal proteolysis. Nevertheless, purified PKC failed to
      alter proteolysis in [14C]S-HRP-loaded isolated lysosomes, suggesting that
      intracellular intermediates are required. PMA induced phosphorylation and
      hepatocyte membrane-to-lysosome redistribution of the myristoylated alanine-rich
      C kinase substrate (MARCKS) protein, raising the possibility that MARCKS mediates
      the PKC-induced inhibition of lysosomal proteolysis.

PMID- 11955958
TI  - A selective decrease in the relative density of parvalbumin-immunoreactive
      neurons in the hippocampus in schizophrenia.
AB  - Neuropathological studies have demonstrated deficits of GABAergic interneurons in
      the hippocampus in schizophrenia. and selective deficits in some GABAergic sub
      populations defined by calcium-binding proteins (CBPs) have been reported in the
      cortex in schizophrenia. In the present study, the relative densities of cells
      immunoreactive for the CBPs parvalbumnin (PV) and calretinin (CR) were determined
      in hippocampal tissue sections taken from patients with schizophrenia, bipolar
      disorder and major depression and from matched control subjects (15 per group).
      No significant difference in the density of CR-immunoreactive neurons was found
      between subject groups. Relative to normal controls, schizophrenic patients
      showed a significant and profound deficit in the relative density of PV
      immunoreactive neurons in all hippocampal sub-fields. These reductions were more
      apparent in male than female schizophrenic patients, and were unrelated to
      antipsychotic drug treatment, age or duration of illness. The density of PV
      immunoreactive neurons did not differ significantly from controls in the
      depression group, although a trend toward decreased relative density of PV
      immunoreactive neurons was apparent in bipolar disorder that reached significance
      in one sub-field. The findings provide further evidence to support a profound and
      selective abnormality of a sub-population of GABAergic neurons in the hippocampus
      in schizophrenia.

PMID- 11955959
TI  - Increased hippocampal volume in schizophrenics' parents with ancestral history of
      schizophrenia.
AB  - OBJECTIVE: Decreased hippocampal volume is one of the hypothesized pathological
      features of schizophrenia, but it is not known if this abnormality is familially
      transmitted. The aim of this study was to measure the hippocampal volume of the
      parents of schizophrenic probands, in relationship to the apparent transmission
      of genetic risk. METHOD: Eighteen subjects from families consisting of a
      schizophrenic proband and two clinically unaffected parents were studied.
      Probands were compared to six control subjects, matched for age, sex, and
      educational level. The six families were selected so that only one parent had an
      ancestral family history of schizophrenia. The volumes of both hippocampi were
      measured by magnetic resonance imaging and adjusted for age and whole brain
      volume. RESULTS: The total hippocampal volumes of the parents with ancestral
      family history of schizophrenia were significantly larger than those of their
      schizophrenic offspring. CONCLUSIONS: This study suggests that decreased
      hippocampal volume in schizophrenia is not a familially transmitted abnormality.
      Rather, it appears that clinically unaffected parents who transmit apparent
      genetic risk for schizophrenia may have increased hippocampal volume, which may
      be a protective factor against the illness.

PMID- 11955960
TI  - Shape distortion of the hippocampus: a possible explanation of the pyramidal cell
      disarray reported in schizophrenia.
AB  - The finding of pyramidal cell disarray in the hippocampus of patients with
      schizophrenia has been disputed by several groups. Conflicting results have been
      attributed to differences in the subtype of patients used, staining method, the
      side of the hippocampus studied and the way cellular disarray has been measured.
      In the present study, we correct for these confounds by using a well-defined
      population of schizophrenic patients (n = 14) and controls (n = 10) in which
      Golgi impregnated material was available. Measurements were performed manually
      according to the method of Kovelman and Scheibel (1984). Pyramidal cell disarray
      for the CA1/prosubicular interface indicated significant differences between
      patients and controls (p = 0.0183). The findings were attributed to a bias
      accrued to referencing measurements in schizophrenics to the distorted
      circumventricular surface of the temporal horn.

PMID- 11955961
TI  - Kraepelinian and non-Kraepelinian schizophrenia subgroup differences in cerebral
      metabolic rate.
AB  - We studied two subtypes of schizophrenia. the Kraepelinian subtype (n = 10)
      characterized by an unremitting and severe course and the non-Kraepelinian
      subtype (n = 17) characterized by a remitting course and some periods of self
      care. Patients were assessed with positron emission tomography (PET) with 18F
      deoxyglucose (FDG) and high-resolution magnetic resonance imaging (MRI). A group
      of 32 age- and sex-matched normal volunteers served as comparison subjects.
      During the FDG tracer uptake period, patients performed a serial verbal learning
      task. MR images were segmented into gray, white and cerebrospinal fluid regions,
      and warped to average normal coordinates. PET images were coregistered to the MR
      images and similarly warpedfor analysis. Kraepelinian subtype patients were
      characterized by lower metabolic rates in the temporal lobe and cingulategyrus.
      and lower fronto/occipital ratios than non-Kraepelinian subtype patients.
      Exploratory statistical probability mapping alsorevealed lower metabolic rates in
      the right striatum in Kraepelinian versus non-Kraepelinian patients. These
      differences couldnot be attributed to differences in age, symptom severity, task
      performance during FDG uptake, or severity of involuntary movements. Factor
      analysis of the cortical surface identified significantly lower temporal lobe
      metabolic rates in Kraepelinian patients than non-Kraepelinian patients. A
      combined frontal/temporal deficit or greater cortical change may be associated
      with poorer longitudinal course.

PMID- 11955962
TI  - Regional changes in brain gray and white matter in patients with schizophrenia
      demonstrated with voxel-based analysis of MRI.
AB  - This study examined regional structural changes in the whole brain in 45
      medicated patients with schizophrenia (23 males and 22 females), comparing with
      42 age- and sex-matched healthy volunteers (22 males and 20 females). Automated
      voxel-based analysis on three-dimensional magnetic resonance imaging (MRI) was
      conducted using statistical parametric mapping (SPM). Compared with the controls,
      relative gray matter in the patients was significantly reduced in the left
      superior temporal, left middle and inferior frontal, right inferior frontal, and
      bilateral anterior cingulate and medial temporal areas. Gray matter reductions in
      the left superior temporal and prefrontal areas were found predominantly in the
      male patients, while the anterior cingulate gray mater reduction was more
      striking in the female patients. On the contrary, significant gray matter
      increases in the patients were found in the parietal areas and the cerebellum. In
      the white matter, significant reduction was found in the bilateral anterior limbs
      of the internal capsule and the superior occipitofrontal fasciculus, whereas the
      bilateral parietal white matter showed significant increases. These results
      suggest that a pathological process in schizophrenia predominantly affects the
      fronto-temporolimbic-paralimbic regions. Reduced white matter in the connecting
      bundles, which was first found in this study, may imply morphological substrates
      for abnormalities in the fronto-thalamic and fronto-temporolimbic connectivity in
      schizophrenia.

PMID- 11955963
TI  - Neuroanatomic characterization of schizoaffective disorder using MRI: a pilot
      study.
AB  - For over 50 years, there has been uncertainty in the conceptual understanding and
      neuropathogenesis of the diagnosis of schizoaffective disorder (SCA). In order to
      better characterize SCA, we performed a quantitative assessment of MRI
      neuroanatomical structures in patients with SCA (n = 12), compared to patients
      with bipolar disorder (BPD) (n = 12) and healthy volunteers (HV) (n = 12).
      Patients diagnosed with SCA exhibited regional abnormalities on the striatum that
      resemble those seen in BPD. This study suggests that SCA has some neuroanatomical
      characteristics similar to BPD.

PMID- 11955964
TI  - Selective reduction of the posterior superior vermis in men with chronic
      schizophrenia.
AB  - Cerebellar structures were measured in 30 chronic schizophrenic men and 18
      healthy men using high resolution MRI. The volume of the posterior superior
      vermis was found to be significantly smaller in the schizophrenic men, but there
      was no difference in other cerebellar regions or the intracranial volume. The
      findings support the view that within the cerebellum the posterior superior
      vermis may be selectively reduced in men with chronic schizophrenia.

PMID- 11955965
TI  - Lack of normal structural asymmetry of the anterior cingulate gyrus in female
      patients with schizophrenia: a volumetric magnetic resonance imaging study.
AB  - We investigated anterior cingulate gyrus (ACG) volume in 40 patients with
      schizophrenia (20 males, 20 females) and 40 age-and sex-matched normal controls
      using three-dimensional magnetic resonance imaging (MRI). Volumes of the whole
      brain and both the gray and white matter of the ACG were measured on consecutive
      coronal 1-mm slices. There was no significant difference between the patients
      with schizophrenia and the normal controls in the whole brain volume. Right ACG
      gray matter volume was significantly reduced in the female patients with
      schizophrenia as compared with the female controls. Furthermore.in the female
      controls, ACG gray matter volume was significantly larger on the right than on
      the left, while this asymmetry was not significant in the female patients. ACG
      white matter findings were similar to those of the ACG gray matter in that the
      volume was significantly larger on the right in the female controls, and this
      normal structural asymmetry was reduced in the female patients. These results
      suggest that gender may play an important role in the structural asymmetry
      anomalies in schizophrenia.

PMID- 11955966
TI  - Reduction of the synaptophysin level but normal levels of glycerophospholipids in
      the gyrus cinguli in schizophrenia.
AB  - The 'membrane hypothesis' of schizophrenia postulates a disturbance in the
      metabolism and structure of membrane phospholipids resulting in a disturbance in
      the function of neuronal membrane proteins. Most studies exploring this
      hypothesis have examined components of peripheral blood. Since it may be
      questioned if these peripheral measurements reflect changes in the brain, we
      studied the fatty acid composition of glycerophospholipids in brain tissue. As a
      marker for synaptic density, we also measured the synaptic vesicle protein
      synaptophysin. Brain tissue (gyrus cinguli) from 11 schizophrenic patients (mean
      age 80 +/- 10 years) and 13 controls (mean age 75 +/- 14 years) was examined. The
      glycerophospholipid fatty acids were determined by gas chromatography.
      Synaptophysin protein level was determined using quantitative immunoblotting
      followed by Western blotting. There were no significant differences between the
      groups in the total or in any individual level of fatty acids, either in the n -
      6 or n - 3 series. The level of synaptophysin was significantly p = (0.002)
      decreased in the schizophrenic group(0.73 + 0.18) as compared with the control
      group (1.02 + 0.21). The normal pattern and concentration of glycerophospholipids
      fatty acids found in the present study do not support the membrane hypothesis of
      schizophrenia. The possibility of a type II error should, however. be considered.
      On the other hand, the reduced synaptophysin' levels in the gyrus cinguli
      demonstrate that biological differences can be revealed in this relatively small
      sample. This also lends further support to the notion that a synaptic disturbance
      or loss is of importance in the pathogenesis of schizophrenia.

PMID- 11955967
TI  - A magnetic resonance imaging study of the adhesio interthalamica in
      schizophrenia.
AB  - Several recent studies have found a relationship between midline cerebral
      malformations (cavum septi pellucidum, absence of the adhesio interthalamica) and
      schizophrenia. In this study, we investigated whether the adhesio interthalamica
      is more often absent in patients with schizophrenia than healthy cases and
      whether the absence of the adhesio interthalamica may be related to the volume of
      the third ventricle. Twenty-six patients (11 male, 15 female) in the
      schizophrenia group and twenty-nine (11 male, 18 female) cases in the control
      group were examined by MRI. The adhesio interthalamica was found to be absent
      more often among patients with schizophrenia compared with control subjects and
      patients without adhesio interthalamica did not have significantly larger third
      ventricle volumes. The absence of the adhesio interthalamica may be important in
      explaining the association between the abnormalities of brain midline structures
      and schizophrenia.

PMID- 11955968
TI  - Is head injury a risk factor for schizophrenia?
AB  - BACKGROUND: The few studies that have examined whether head injury is a risk
      factor for later schizophrenia have had important methodological problems.
      METHOD: We examined the rates of head injury among 8288 persons in the 15 years
      up to their first admission with schizophrenia and compared them with 82880 age-
      and gender-matched controls. We used hospitalization for concussion or severe
      head injury as a definition of head injury. We controlled for any generally
      altered accident proneness prior to schizophrenia by also comparing the groups
      with respect to exposition to fractures not involving the skull or spine.
      RESULTS: Males with schizophrenia had significantly reduced exposure to
      concussion (OR = 0.864, p = 0.024), whereas females had significantly increased
      exposure (OR = 1.322, p = 0.025). No differences were found as regards severe
      head injury. Males had significantly reduced risk of other fractures (OR = 0.616,
      p < 0.0001), whereas the risk in females did not differ from controls (OR =
      1.154, p = 0.189). After adjusting head injury with the risk for other fractures,
      both concussion and severe head injury were significantly increased in males (OR
      = 1.501, p < 0.001 and OR = 1.516. p < 0.001, respectively) but not in females
      (OR = 1.15, p = 0.413 and OR = 0.819, p = 0.442, respectively). CONCLUSION: Our
      results do not exclude that for males, head injury may contribute to the risk for
      schizophrenia in a limited number of cases. This relation may also exist for
      females, but it is paralleled by an increased liability to traumas in general.
      Premorbid general accident proneness requires consideration when studying this
      association.

PMID- 11955969
TI  - Head size and schizophrenia.
AB  - There is a small but intriguing body of literature which suggests that head size
      may be reduced in patients with schizophrenia. This literature sits alongside
      more substantial and compelling evidence that there is a reduction in cerebral
      volume in schizophrenia. As an extension of earlier work, measures of
      extracranial head size derived from standard anthropometric approaches were
      assessed in 44 patients and 46 control subjects. Head size was found to be normal
      in schizophrenia. The relationship of brain size to head size is elaborated.

PMID- 11955970
TI  - Clinical and neuropsychological correlates of the P300 in schizophrenia.
AB  - We investigated the relationship between the P300, neuropsychological test
      performance and symptomatology in recent-onset schizophrenic patients (n = 45) to
      gain insight into underlying mechanisms of abnormal P300 in schizophrenia. The
      P300 was recorded in two sessions with an intermission of five minutes, at the
      midline frontal, central and parietal electrode site. P300 amplitude and latency
      were compared with those obtained in 25 controls. Twenty patients were treated
      with olanzapine and 19 patients with risperidone. P300 amplitude was smaller and
      latency longer in patients than in controls. In the patient group, parietal P300
      amplitude reduction was related to poorer performance on neuropsychological tests
      of memory. Frontal P300 amplitude reduction was related to impaired selective
      attention. In patients with negative symptomatology, P300 amplitude was reduced
      in the second P300 session compared with the first. Patients on risperidone
      demonstrated a smaller parietal P300 amplitude than patients using olanzapine.
      Reduced parietal P300 amplitude could signify a dysfunction in the continuous
      memory updating of current events. Negative symptomatology may be associated with
      a time dependent decrease in neuronal firing, as indicated by reduced P300
      amplitude in the second P300 session.

PMID- 11955971
TI  - Altered performance of schizophrenia patients in an auditory detection and
      discrimination task: exploring the 'self-monitoring' model of hallucination.
AB  - It has been suggested that perceptual hallucination results from a bias in
      attributing a self-generated event to an external source. The 'self-monitoring'
      model proposes that the impairment arises from a defective corollary discharge in
      perceptual decisions. However, psychophysical studies in schizophrenia patients
      have not found consistent support for the model. We re-explored this issue by
      including subjects with mood disorders as patient controls and employed signals
      of variable intensities in an auditory detection and discrimination task. Using
      signal detection theory, we found decreased sensitivity in auditory detection and
      discrimination in schizophrenia patients, as compared to control subjects.
      Moreover, the psychometric functions of schizophrenics had a shallower slope than
      those of the controls. According to the uncertainty theory of signal detection,
      this suggested that schizophrenia patients monitored a smaller number of
      perceptual channels. On the other hand, hallucinating and non-hallucinating
      schizophrenia patients did not differ from each other, nor did they as a group
      differ from control subjects in terms of response bias. Overall, our results do
      not support the idea that hallucination results from an altered bias in the
      online processing of perceptual signals.

PMID- 11955973
TI  - Prepulse inhibition of the startle response in risperidone-treated patients:
      comparison with typical antipsychotics.
AB  - Individuals with schizophrenia are known to show deficits in prepulse inhibition
      (PPI) of the startle response. PPI refers to a response suppression in reaction
      to a strong startling stimulus, if preceded briefly by a weak non-startling
      stimulus and represents a well-established animal model to investigate
      information processing deficits in schizophrenia. This study examined PPI of the
      startle acoustic response in schizophrenic patients given typical antipsychotics
      or a second generation atypical antipsychotic, risperidone, using a naturalistic
      between-subjects design. Two groups of male schizophrenic patients: (i) stable on
      a range of typical antipsychotics (n = 20), and (ii) stable on risperidone (n =
      10) were tested for PPI (prepulse-to-pulse intervals: 30, 60, and 120 ms,
      prepulses 15 dB above the background) of the acoustic startle response, and
      compared with a group of healthy male subjects (n = 20). Patients on typical
      antipsychotics showed significantly less PPI with 30 and 60 ms prepulse trials
      than healthy subjects. Risperidone-treated patients did not differ from healthy
      subjects for PPI with any prepulse trials. Further longitudinal within-subject
      studies are now required to examine whether risperidone is superior to typical
      antipsychotics in improving information processing functions, as assessed by PPI
      of the acoustic startle response, in treatment-responsive male patients with
      schizophrenia.

PMID- 11955972
TI  - Stability of the acoustic startle reflex, prepulse inhibition, and habituation in
      schizophrenia.
AB  - Prepulse inhibition (PPI) of the acoustic startle reflex has been proposed as a
      neurophysiological measure of sensorimotor gating. There is high test-retest
      reliability of both startle magnitude and PPI in non-psychiatric subjects. The
      present study examined the stability of the acoustic startle reflex and its
      modulation in patients with schizophrenia. Startle measurements were performed in
      19 chronic schizophrenic patients on stable medications and 24 healthy control
      subjects, three times at one-month intervals. PPI trials with various intervals
      between the prepulse and the startle stimulus (30, 60. 120, 240, and 2000 ms)
      were used. Intraclass correlation coefficients (ICC) were computed to assess
      stability. There was a good test-retest reliability of PPI in both schizophrenic
      patients (Mean ICC: 0.75) and control subjects (Mean ICC: 0.71). Acoustic startle
      magnitude was the most stable measure across sessions (Mean ICC schizophrenics:
      0.89; Mean ICC controls: 0.89). In both groups, a good test-retest reliability
      was found in the startle latencies. Habituation and prepulse-induced shortening
      of latencies exhibited moderate stability. Schizophrenic patients exhibited
      significantly less PPI than control subjects in the 60 ms prepulse condition.
      This PPI deficit was evident in all three sessions. These results indicate that
      PPI is a stable neurobehavioral measure in chronic schizophrenic patients in the
      absence of changes in clinical state.

PMID- 11955975
TI  - Visual scanpaths to positive and negative facial emotions in an outpatient
      schizophrenia sample.
AB  - We used a psychophysiological marker of visual attention (visual scanpath) to
      investigate facial emotion processing in schizophrenia (n= 65) and healthy
      control (n = 61) groups. Visual scanpaths to 'happy', *sad' and 'neutral' faces
      (two exposures each) were recorded using video-oculography. Emotion recognition
      accuracy was assessed under both 'difficult' (exposure 1) and 'limited choice'
      (exposure 2) conditions. Compared to controls, schizophrenia subjects showed
      'restricted' scanning and reduced attention to salient facial features (eyes,
      nose, mouth), that was particularly apparent for happy and neutral faces:
      accuracy was correspondingly reduced for the 'difficult' condition. The
      schizophrenia deficit in positive emotion perception may reflect a failure to
      integrate salient features due to dysfunctions in local processing of detailed,
      relevant information (fewer fixations, less attention to facial features), and in
      the networks that synchronise local and global processing of biologically
      relevant face stimuli (generally restricted scanning style).

PMID- 11955974
TI  - Latent inhibition and schizophrenia: Pavlovian conditioning of autonomic
      responses.
AB  - Latent inhibition (LI) is an important model for understanding cognitive deficits
      in schizophrenia. Disruption of LI is thought to result from an inability to
      ignore irrelevant stimuli. The study investigated LI in schizophrenic patients by
      using Pavlovian conditioning of electrodermal responses in a complete within
      subject design. Thirty-two schizophrenic patients (16 acute, unmedicated and 16
      medicated patients) and 16 healthy control subjects (matched with respect to age
      and gender) participated in the study. The experiment consisted of two stages:
      preexposure and conditioning. During preexposure two visual stimuli were
      presented. one of which served as the to-be-conditioned stimulus (CSp + ) and the
      other one was the not-to-be-conditioned stimulus (CSp - ) during the following
      conditioning ( = acquisition). During acquisition, two novel visual stimuli(CSn +
      and CSn - ) were introduced. A reaction time task was used as the unconditioned
      stimulus (US). LI was defined as the difference in response differentiation
      observed between preexposed and non-preexposed sets of CS + and CS - . During
      preexposure, the schizophrenic patients did not differ in electrodermal
      responding from the control subjects, neither concerning the extent of orienting
      nor the course of habituation. The exposure to novel stimuli at the beginning of
      the acquisition elicited reduced orienting responses in unmedicated patients
      compared to medicated patients and control subjects. LI was observed in medicated
      schizophrenic patients and healthy controls, but not in acute unmedicated
      patients. Furthermore LI was found to be correlated with the duration of illness:
      it was attenuated in patients who had suffered their first psychotic episode.

PMID- 11955976
TI  - Perception of happy and sad facial expressions in chronic schizophrenia: evidence
      for two evaluative systems.
AB  - BACKGROUND: Persons suffering from schizophrenia have impaired perception of
      emotional expressions, but it is not clear whether this is part of a generalized
      deficit in cognitive function. AIM: To test for existence of emotion-specific
      deficits by studying the effects of valence on recognition of facial emotional
      expressions. METHODS: 24 male subjects suffering from chronic schizophrenia were
      examined with two tests of perception of emotion: the Penn Emotion Acuity Test
      (PEAT 40) and the Emotion Differentiation Task (EMODIFF). Clinical state was
      assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Scale
      for the Assessment of Positive Symptoms (SAPS), visual memory with the Benton
      Visual Retention Test (BVRT) and motor function with the finger tapping test.
      RESULTS: Identification of happy facial expressions showed significant negative
      correlation with age, cumulated time in hospital and length of current
      hospitalization; positive correlations were found with visual retention and
      finger tapping scores. Identification of sad facial expressions showed
      significant correlation only with cumulated time in hospital while identification
      of neutral facial expressions showed no significant correlations. Discrimination
      between degrees of happy but not sad facial expression showed a positive
      correlation with negative symptoms. CONCLUSION: Perception of happy and sad
      emotion relates differently to significant illness parameters. This
      differentiability supports the existence of an emotion-specific deficit in
      perception of emotions in schizophrenia and of separate channels for processing
      positive and negative emotions.

PMID- 11955978
TI  - Sensory processing in schizophrenia: missing and avoiding information.
AB  - The possible coexistence of supersensitivity and overinhibition (Schizophrenia:
      Origins, Processes, Treatment and Outcome (1993) 335-350) in schizophrenia was
      studied using the Adult Sensory Profile as a measure of Dunn's (Infants Young
      Children 9 (1997) 23-25) model of sensory processing. The quadrant model
      describes sensory sensitivity, sensation avoiding, low registration and sensation
      seeking as behavioral responses to sensation. Individuals with schizophrenia (N =
      27), bipolar disorder (N = 30) and mentally healthy controls (N = 29) were
      compared using the Adult Sensory Profile. When compared to the mentally healthy
      group, the results indicated that both the schizophrenia group and the bipolar
      disorder group had higher scores on sensation avoiding. The schizophrenia group
      also had higher scores on low registration and lower scores on sensation seeking
      than the mentally health group. There were no differences between the
      schizophrenia and bipolar disorder group. According to the findings of this
      study, individuals with schizophrenia tend to miss available sensory stimuli.
      When stimuli are indeed detected, they are often avoided.

PMID- 11955977
TI  - Evaluation of expressed emotion in schizophrenia: a comparison of Caucasians and
      Mexican-Americans.
AB  - Social desirability, while a recognized source of respondent bias among Mexican
      Americans, has not been evaluated as an explanation for the lower rate of high
      expressed emotion (EE) found in the family members of Mexican-Americans versus
      Caucasians with schizophrenia. In this study, we tested the hypothesis that the
      lower rate of high EE (hostility and criticism) among Mexican-Americans was the
      result of cultural factors impacting on how information was reported by the
      Mexican-American relative of a patient with schizophrenia. We compared the
      ratings of EE between Caucasian (N = 17) and Mexican-American (N = 44) patients
      with schizophrenia or schizoaffective disorder and their key relatives using the
      level of expressed emotion (LEE) scale (paper and pencil instrument rated by the
      patient and relative separately) and the Five Minute Speech Sample (observational
      experimenter rated). The ability of the various measures to predict relapse over
      two years was also examined. Contrary to our hypothesis, there were no
      differences between patient and family measures within ethnic group. Mexican
      American patients and relatives reported lower rates of high EE than Caucasians
      across all measures. High EE predicted relapse across measures for Caucasian
      participants, but did not predict relapse for Mexican-Americans on any of the
      measurement instruments. We discuss the implications of these findings on cross
      cultural research and family interventions for individuals with psychotic
      disorders.

PMID- 11955979
TI  - Color discrimination in schizophrenia.
AB  - Neuropsychiatric conditions that involve dopaminergic depletion have been
      associated with color discrimination deficits along the blue-hue (tritan, or
      short-wavelength-sensitive) axis. Because dopamine dysregulation may be a major
      factor in schizophrenia, we investigated color vision in this disorder. The
      performance of males with schizophrenia (SZ, n = 16) and normal male control
      subjects (CS, n = 14) was evaluated on five measures of color discrimination. SZ
      made more hue discrimination errors than CS, but no pattern emerged regarding a
      hue-specific axis of deficit. Dosage of anti-psychotic medication was not
      correlated with performance on hue discrimination. These results suggest that in
      medicated patients with schizophrenia, the dopaminergic disturbance, which may
      involve system hyperactivity, does not produce tritan-specific color deficits
      that have been observed in disorders involving dopaminergic hypoactivity.

PMID- 11955980
TI  - Neuromuscular disorders associated with static lumbar flexion: a feline model.
AB  - Static flexion of the lumbar spine with constant load applied to the viscoelastic
      structures for 20 minutes and for 50 minutes resulted in development of spasms
      and inhibition in the multifidus muscles (e.g., deep erector spinae) and in creep
      of the supraspinous ligament in the feline model. The development of spasms and
      inhibition was not dependent on load magnitude. It is suggested that occupational
      and sports activities which require prolonged static lumbar flexion within the
      physiological range can cause a "sprain"-like injury to the ligaments, which in
      turn reflexively induce spasms and inhibition in some erector spinae muscles.
      Such disorder may take a long time to recover, in the order of days to weeks,
      depending on the level of creep developed in the tissues.

PMID- 11955981
TI  - Evaluation of measurement strategies to increase the reliability of EMG indices
      to assess back muscle fatigue and recovery.
AB  - The purpose of this study was to assess different measurement strategies to
      increase the reliability of different electromyographic (EMG) indices developed
      for the assessment of back muscle impairments. Forty male volunteers (20 controls
      and 20 chronic low back pain patients) were assessed on three sessions at least 2
      days apart within 2 weeks. Surface EMG signals were recorded from four pairs
      (bilaterally) of back muscles (multifidus at the L5 level, iliocostalis lumborum
      at L3, and longissimus at L1 and T10) while the subjects performed, in a static
      dynamometer, two static trunk extension tasks at 75% of the maximal voluntary
      contraction separated by a 60 s rest period: (1) a 30 s fatigue task and (2) a 5
      s recovery task. Different EMG indices (based on individual muscles or averaged
      across bilateral homologous muscles or across all muscles) were computed to
      evaluate muscular fatigue and recovery. Intra-class correlation coefficient (ICC)
      and standard error of measurement (SEM) in percentage of the grand mean were
      calculated for each EMG variable. Reliable EMG indices are achieved for both
      healthy and chronic low back pain subjects when (1) electrodes are positioned on
      medial back muscles (multifidus at the L5 level and longissimus at L1) and (2)
      measures are averaged across bilateral muscles and/or across two fatigue tests
      performed within a session. The most reliable EMG indices were the bilateral
      average of medial back muscles (ICC range: 0.68-0.91; SEM range: 5-35%) and the
      average of all back muscles (ICC range: 0.77-0.91; SEM range: 5-30%). The
      averaging of measures across two fatigue tests is predicted to increase the
      reliability by about 13%. With regards to EMG indices of fatigue, the
      identification of the most fatigable muscle also lead to satisfactory results
      (ICC range: 0.74-0.79; SEM range: 21-26%). The assessment of back muscle
      impairments through EMG analysis necessitates the use of multiple electrodes to
      achieve reliable results.

PMID- 11955982
TI  - SEMG power spectrum changes during a sustained 50% Maximum Voluntary Isometric
      Torque do not depend upon the prior knowledge of the exercise duration.
AB  - Endurance time (Tlim) is a relevant indicator of muscular resistance to fatigue.
      It has been recently shown that SEMG changes computed during shorter periods (sub
      maximal durations) than the whole test duration could serve to predict Tlim. The
      aim of the present study was to test whether the prior knowledge of the sub
      maximal duration had any influence on Tlim prediction throughout SEMG changes.
      For this purpose, we compared myoelectric changes estimated over a 30-s isometric
      contraction whose duration was known by the subjects, to those changes measured
      during the first 30 s of a test prolonged until exhaustion. The effort intensity
      was set at 50% of the maximal voluntary isometric torque (MVIT). The myoelectric
      manifestations of muscle fatigue appeared to change in a similar way during both
      sessions for temporal and spectral analyses. In conclusion, the prior knowledge
      of the duration of sustained isometric contraction did not influence the motor
      unit recruitment strategy throughout surface EMG evaluation. These results
      confirmed that the use of SEMG changes computed over shorter periods than
      expected endurance time may be applied to investigate the capability of the
      initial rate of SEMG changes to predict muscle endurance capacity at 50%MVIT.
      This may be of particular interest for patient evaluation in the clinical field.

PMID- 11955983
TI  - Electromyogram median frequency, spectral compression and muscle fibre conduction
      velocity during sustained sub-maximal contraction of the brachioradialis muscle.
AB  - Changes in the median frequency of the power spectrum of the surface
      electromyogram (EMG) are commonly used to detect muscle fatigue. Previous
      research has indicated that changes in the median frequency are related to
      decreases in muscle fibre conduction velocity (MFCV) during sustained fatiguing
      contractions. However, in experimental studies the median frequency has been
      consistently observed to decrease by a relatively greater amount than MFCV. In
      this paper, a new estimate of EMG frequency compression, the Spectral Compression
      Estimate (SCE), is compared with the median frequency of the EMG power spectrum,
      the median frequency of the EMG amplitude spectrum and MFCV measured during
      sustained, isometric, fatiguing contractions of the brachioradialis muscle at 30,
      50 and 80% maximum voluntary contraction (MVC). The SCE is found to provide a
      better estimate of the observed changes in MFCV than the median frequency of
      either the EMG power spectrum or EMG amplitude spectrum.

PMID- 11955984
TI  - Gender differences in active musculoskeletal stiffness. Part I. Quantification in
      controlled measurements of knee joint dynamics.
AB  - Active females demonstrate increased risk for musculoskeletal injuries relative
      to equivalently-trained males. Although gender differences in factors such as
      passive laxity, skeletal geometry and kinematics have been examined, the effect
      of gender on active muscle stiffness has not been reported. Stiffness of the
      active quadriceps and hamstrings musculature were recorded during isometric knee
      flexion and extension exertions from twelve male and eleven female subjects. A
      second-order biomechanical model of joint dynamics was used to quantify stiffness
      from the transient motion response to an angular perturbation of the lower-leg.
      Female subjects demonstrated reduced active stiffness relative to male subjects
      at all torque levels, with levels 56-73% of the males. Effective stiffness
      increased linearly with the torque load, with stiffness increasing at a rate of
      3.3 Nm/rad per unit of knee moment in knee flexion exertions (hamstrings) and 6.6
      Nm/rad per unit of knee moment extension exertions (quadriceps). To account for
      gender differences in applied moment associated with leg mass, regressions
      analyses were completed that demonstrated a gender difference in the slope of
      stiffness-versus-knee moment relation. Further research is necessary to identify
      the cause of the observed biomechanical difference and implications for
      controlling injury.

PMID- 11955985
TI  - Gender differences in active musculoskeletal stiffness. Part II. Quantification
      of leg stiffness during functional hopping tasks.
AB  - Leg stiffness was compared between age-matched males and females during hopping
      at preferred and controlled frequencies. Stiffness was defined as the linear
      regression slope between the vertical center of mass (COM) displacement and
      ground-reaction forces recorded from a force plate during the stance phase of the
      hopping task. Results demonstrate that subjects modulated the vertical
      displacement of the COM during ground contact in relation to the square of
      hopping frequency. This supports the accuracy of the spring-mass oscillator as a
      representative model of hopping. It also maintained peak vertical ground-reaction
      load at approximately three times body weight. Leg stiffness values in males
      (33.9+/-8.7 kN/m) were significantly (p<0.01) greater than in females (26.3+/-6.5
      kN/m) at each of three hopping frequencies, 3.0, 2.5 Hz, and a preferred hopping
      rate. In the spring-mass oscillator model leg stiffness and body mass are related
      to the frequency of motion. Thus male subjects necessarily recruited greater leg
      stiffness to drive their heavier body mass at the same frequency as the lighter
      female subjects during the controlled frequency trials. However, in the preferred
      hopping condition the stiffness was not constrained by the task because frequency
      was self-selected. Nonetheless, both male and female subjects hopped at
      statistically similar preferred frequencies (2.34+/-0.22 Hz), therefore, the
      females continued to demonstrate less leg stiffness. Recognizing the active
      muscle stiffness contributes to biomechanical stability as well as leg stiffness,
      these results may provide insight into the gender bias in risk of musculoskeletal
      knee injury.

PMID- 11955986
TI  - Variations in the relationship between the frequency content of EMG signals and
      the rate of torque development in voluntary and elicited contractions.
AB  - Our purpose was to characterize the relationship between EMG mean power frequency
      (MPF) or median frequency (MF) and rate of torque development in voluntary
      ballistic and electrically elicited isometric contractions. Twenty-three healthy
      adults participated in two sets of experiments performed on elbow flexor muscles.
      For Experiment 1, subjects were asked to generate voluntary ballistic
      contractions by reaching four different target torque levels (20, 40, 60 and 100%
      of the maximal voluntary contraction (MVC)) as fast as they could. For Experiment
      2, electrical (M-waves) and mechanical (twitches) responses to electrical
      stimulation of the nerves supplying the biceps brachii and brachioradialis
      muscles were recorded with the subjects at rest and with a background isometric
      contraction of 15% MVC. MPF, MF and rate of torque development (% MVC/s) were
      calculated for both voluntary and elicited contractions. Significant positive
      correlations were observed between MPF and rate of torque development for the
      voluntary contractions, whereas significant negative correlations were observed
      between the two variables for elicited contractions. This suggests that factors
      other than muscle fiber composition influence the frequency content of EMG
      signals and/or the rate of torque development, and that the effect of these
      factors will vary between voluntary and elicited contractions.

PMID- 11955987
TI  - Automated localization of nerve damage: hypothesis, technique and performance
      appraisal.
AB  - Needle-EMG is a common procedure performed and relied on by neurologists,
      physiatrists and neurosurgeons to localize focal nerve damage. However, despite
      its popularity, there is no standardization of this diagnostic process rendering
      it error prone. An automated diagnostic program may help the electromyographer by
      providing an objective second opinion and a statistical measure of its strength.
      Such a program is presented and evaluated in this manuscript. The
      electromyographer samples a set of muscles and grades each muscle for neuropathic
      changes. The Program accepts the electromyographer's graded muscle set. The
      Program then compares it to muscle-sets derived from all possible combinations of
      nerve damage and finds that combination that results in the best match. The
      latter is the anatomical diagnosis. Eighty-five cases from the literature, each
      with an impartial expert diagnosis, were analyzed using this Program. The Program
      precisely matched the expert electromyographers' diagnoses in 79% of the cases,
      partially matched in 15%, and did not match in 6% of the cases. In the latter,
      not necessarily the Program was in error. The Program proved to be a reliable
      diagnostic tool that may help electromyographers by offering a second opinion. It
      may also assist in teaching of residents and fellows.

PMID- 11955988
TI  - Blink reflex in end-stage-renal disease patients undergoing hemodialysis.
AB  - This study analyses the blink reflex in 20 adult male patients with terminal
      chronic renal failure undergoing hemodialysis. Abnormalities were found in ten
      patients (50%), eight of them with conduction studies showing axonal peripheral
      neuropathy. Dialysis time was longer for patients with blink reflex alterations
      (median 55.1 months) than for patients with normal blink reflex (median 36.3
      months). Different types of early R1 and late R2 component abnormalities were
      recorded. The late response abnormalities may indicate subclinical functional or
      anatomical impairment of the low brainstem reticular formation in patients with
      chronic renal failure.

PMID- 11955989
TI  - Successive signal representation in noise in dyslexics.

PMID- 11955990
TI  - Spatial congruence of neuronavigated transcranial magnetic stimulation and
      functional neuroimaging.
AB  - OBJECTIVES: Transcranial magnetic stimulation (TMS) is progressively gaining
      relevance as a tool in cognitive neuroscience and clinical research. However,
      most studies in this field do not consider individual anatomy. Neuronavigational
      devices allow to guide the coil to a specific cortical area, predetermined by
      functional magnetic resonance imaging (fMRI). Therefore, it is crucial to know
      whether the area of a certain function as identified by fMRI corresponds to the
      area where the TMS should be placed in order to influence this function. METHODS:
      We investigated the spatial relation between the cortical area activated by a
      motor task in fMRI and the area of magnetically evoked motor potentials (MEP) in
      8 subjects, using a spacing of 5x5 mm. A neuronavigational system was adapted for
      coil positioning and for the registration of the stimulation coordinates.
      RESULTS: A spatial divergence of the centers of gravity from fMRI and MEP was
      found with a mean distance of about 10 mm, with the MEP centers being, by a mean
      derivation of 7.5 mm, consistently anterior to the center of fMRI activation.
      However, regarding MEP areas and fMRI activities, a large overlap was found for
      stimulation intensities of both 110 and 120% motor threshold. CONCLUSIONS: The
      combination of fMRI and neuronavigated TMS is useful for non-invasive
      investigation of individual cortical functions predetermined by fMRI. Whereas
      both are spatially by and large congruent, discrepencies in the exact spatial
      relation between MEP and fMRI areas should be considered and further studied.

PMID- 11955991
TI  - Comparison of direct and indirect measurements of the central motor conduction
      time in the monkey.
AB  - OBJECTIVE: The goal of the present study was to compare the indirect estimate of
      the central motor conduction time (CMCT) with direct measurement of the
      corticospinal conduction time between the motor cortex and cervical enlargement
      in macaque monkeys. METHODS: Responses to transcranial magnetic stimulation of
      the motor cortex were recorded from intrinsic hand muscles in adult macaque
      monkeys. The CMCT was calculated by subtracting the peripheral conduction time,
      measured with the F-wave method, from the latency of the motor evoked potentials
      (MEPs). In two monkeys, the actual conduction time between the motor cortex and
      cervical enlargement was measured directly by different invasive techniques.
      RESULTS: We found that the indirect calculation of CMCT overestimates the
      corticospinal conduction time to a significant extent. CONCLUSIONS: One possible
      source of error is an underestimate of the MEP peripheral conduction time. A
      collision test confirmed this hypothesis and showed that only a marginal
      proportion of the motoneurones that respond to a weak corticospinal input also
      participate in the F-wave. A more accurate estimate of the CMCT could be obtained
      by using the longest F-wave latency, rather than the shortest, to calculate the
      peripheral conduction time.

PMID- 11955992
TI  - Motor evoked responses from the thigh muscles to the stimulation of the upper
      limb nerves in patients with late poliomyelitis.
AB  - OBJECTIVES: To demonstrate a clear-cut M response recorded from the severely
      affected thigh muscles to the stimulation of the upper limb nerves in a serial of
      patients with late poliomyelitis. METHODS: Fifteen patients with late
      poliomyelitis, 7 patients with spinal cord disorders and 11 control subjects were
      included. Evoked muscle responses were investigated in quadriceps femoris and/or
      thigh adductor muscles to the stimulation of the brachial plexus, median and
      ulnar nerves. RESULTS: Evoked muscle responses were obtained from the thigh
      muscles in all 12 late polio patients with proximal lower extremity involvement.
      The response could not be recorded from the thigh muscles neither in the 3 polio
      patients with upper extremity involvement nor in the healthy control subjects and
      in patients with other spinal cord disorders of anterior horn cell. CONCLUSIONS:
      It is proposed that the electrical stimulation of the arm nerves produce
      interlimb descending muscle responses in the severely affected atrophic thigh
      muscles of the patients with late polio. This finding suggests that there might
      be a focal and/or specific loss of inhibitory interneurons between injured and
      normal motor neurons and increased facilitatory synaptic action at the end of
      long propriospinal descending fibers in the case of late poliomyelitis.

PMID- 11955993
TI  - Abnormal neural encoding of repeated speech stimuli in noise in children with
      learning problems.
AB  - OBJECTIVES: This study investigated whether neurophysiologic responses to
      repeated speech stimuli, presented in quiet and noise, differed between normal
      children (NL) and children with learning problems (LP). METHODS: Subjects were
      normal-hearing, school-age children. NL subjects scored significantly better than
      LP subjects on measures of reading, spelling and speech sound discrimination.
      Stimuli (40 ms /da/) were presented to the right ear at 80 dB SPL. Stimuli were
      presented in trains of four, separated within trains by 360 ms. The interval
      between trains was 1060 ms. Stimuli were presented in quiet and in white noise
      (S/N+15). Cortical responses were recorded from an electrode placed along the
      midline at Cz. RESULTS: Correlations between the first and 4th responses were
      lower in noise than in quiet for LP subjects only. Response correlations in quiet
      were no different between groups. There were no root-mean-square (RMS) amplitude
      differences between groups. CONCLUSIONS: Response correlation in noise suggested
      that the LP population consisted of two subgroups, one whose responses appeared
      relatively normal, and another whose responses were severely degraded by
      repetition in noise. Response correlations in noise were related to behavioral
      measures of auditory processing and spelling. These findings suggest that
      abnormal, asynchronous, auditory cortical encoding may underlie some language
      based learning problems.

PMID- 11955994
TI  - Mismatch negativity evoked by the McGurk-MacDonald effect: a phonetic
      representation within short-term memory.
AB  - OBJECTIVES: The McGurk-MacDonald illusory percept is obtained by dubbing an
      incongruent articulatory movement on an auditory phoneme. This type of
      audiovisual speech perception contributes to the assessment of theories of speech
      perception. The mismatch negativity (MMN) reflects the detection of a deviant
      stimulus within the auditory short-term memory and besides an acoustic component,
      possesses, under certain conditions, a phonetic one. The present study assessed
      the existence of an MMN evoked by McGurk-MacDonald percepts elicited by
      audiovisual stimuli with constant auditory components. METHODS: Cortical evoked
      potentials were recorded using the oddball paradigm on 8 adults in 3 experimental
      conditions: auditory alone, visual alone and audiovisual stimulation. Obtaining
      illusory percepts was confirmed in an additional psychophysical condition.
      RESULTS: The auditory deviant syllables and the audiovisual incongruent syllables
      elicited a significant MMN at Fz. In the visual condition, no negativity was
      observed either at Fz, or at O(z). CONCLUSIONS: An MMN can be evoked by visual
      articulatory deviants, provided they are presented in a suitable auditory context
      leading to a phonetically significant interaction. The recording of an MMN
      elicited by illusory McGurk percepts suggests that audiovisual integration
      mechanisms in speech take place rather early during the perceptual processes.

PMID- 11955995
TI  - Electrophysiology of spatial scene analysis: the mismatch negativity (MMN) is
      sensitive to the ventriloquism illusion.
AB  - OBJECTIVES: The ventriloquism effect is the tendency to underestimate the spatial
      separation between synchronous auditory and visual signals moderately separated
      in space. If, as it is thought, this effect is pre-attentive, it could modulate
      the mismatch negativity (MMN) that indexes the automatic, pre-attentive detection
      of deviant auditory stimuli rarely occurring in a sequence of standard stimuli.
      We assessed the existence of an MMN evoked by auditory and visual signals made up
      of standard sounds coming from the same location as the visual signal and deviant
      sounds coming from lateral deviations (20 or 60 degrees). As first observed in a
      behavioral study, a ventriloquism effect occurred for 20 degrees spatial
      separation but not for 60 degrees. METHODS: Cortical evoked potentials were
      recorded using the oddball paradigm on 8 adults in auditory alone and audiovisual
      conditions. RESULTS: In the auditory alone condition, each spatial localization
      contrast elicited a significant MMN. In the audiovisual condition, a significant
      MMN was only evoked for the 60 degrees contrasts. CONCLUSIONS: The MMN evoked by
      spatial separation contrasts (20 and 60 degrees) in the auditory alone condition
      was suppressed by the corresponding audiovisual condition only when the latter
      yielded a ventriloquism effect, suggesting that this effect occurs at an early
      perceptual level.

PMID- 11955996
TI  - Mismatch negativity to single and multiple pitch-deviant tones in regular and
      pseudo-random complex tone sequences.
AB  - OBJECTIVES: To determine whether the process responsible for the mismatch
      negativity (MMN) might be involved in the analysis of temporal sound patterns for
      information. METHODS: Synthesized musical instrument tones of 'clarinet' timbre
      were delivered in a continuous sequence at 16 tones/s, such that there was
      virtually no N1 potential to each individual tone. The standard sequence
      comprised 4 or 5 adjacent notes of the diatonic scale, presented either as a
      regularly repeated, rising pattern or pseudo-randomly. The deviant stimuli were 1
      5 consecutive tones of higher pitch than the standards. RESULTS: A MMN was evoked
      by a single deviant tone, 1 or 5 semitones above the pitch range of the
      standards. The response to the 5-semitone deviant was significantly larger (mean
      of 7.3 microV) when the standard pattern was regular as compared with pseudo
      random. The MMN latency, on the other hand, was only influenced by the magnitude
      of pitch deviation. A second MMN was evoked by a second deviant tone, immediately
      (SOA 62.5 ms) following the first. Further consecutive MMNs were not consistently
      evoked. CONCLUSIONS: The large amplitude of these MMNs can be attributed to the
      use of complex tones, continuous presentation and a rapid rate of pitch changes,
      such that no waveform subtraction was required. Over and above the probability
      with which each individual tone occurs in the standard sequence, the mismatch
      process is influenced by its temporal structure, i.e. can be regarded as a
      temporal pattern analyzer. Contrary to the findings of some other groups, we
      found that two consecutive deviants can evoke an MMN, even at high rates of
      presentation such that both occur within the postulated 'temporal window of
      integration' of ca. 170 ms. These findings suggest that the mismatch process
      might be involved in the extraction of sequential information from repetitive and
      non-repetitive sound patterns.

PMID- 11955997
TI  - Selective effects of ageing on vestibular-dependent lower limb responses
      following galvanic stimulation.
AB  - OBJECTIVES: To examine the influence of ageing on electromyographic (EMG)
      responses to galvanic vestibular stimulation (GVS) in the lower limbs and to
      define normal values. METHODS: EMG responses to 4 mA/20 ms transmastoid binaural
      GVS were recorded from the soleus muscles of 70 healthy adults aged 24-85 years.
      Short (SL) and medium latency (ML) vestibular-dependent reflex latencies and
      amplitudes were measured from averaged rectified EMG. Side to side differences
      were examined in 30 subjects, using monaural stimulation, and expressed as an
      asymmetry ratio (AR). RESULTS: SL reflexes to transmastoid binaural stimulation
      were absent in 10 of the 25 subjects over the age of 60. ML responses were
      present in all subjects. SL reflex amplitudes decreased from 24.4+/-12.4% (mean+/
      SD) in the 3rd decade to 7.6+/-6.2% in the 8th and 9th decades. The ML reflex
      amplitudes showed a tendency to increase with age. The mean AR for SL reflex
      amplitudes increased from 12.1% in the 3rd decade to 80.7% in the 8th and 9th
      decades but that for ML amplitudes did not change significantly. The average SL
      and ML response onset latencies were 56.5+/-7.5 and 97.2+/-9.4 ms. SL onset
      latencies were significantly delayed with age. Both SL and ML responses were
      highly reproducible between experiments. CONCLUSIONS: SL and ML responses behave
      differently in response to age. The decrease in SL reflex amplitudes correlates
      well with previously described age-related morphological changes. Preservation of
      the ML reflex may reflect central adaptation to reduced afferent input. SL and ML
      responses are potentially useful measures of vestibular-spinal function, which
      may have a role in the assessment of older subjects with dysequilibrium. These
      reflexes need to be interpreted in the context of age.

PMID- 11955998
TI  - New concept for the recovery function of short-latency somatosensory evoked
      cortical potentials following median nerve stimulation.
AB  - OBJECTIVES: We investigated the recovery function of the cortical components of
      somatosensory evoked potentials (SEP) at a very short interstimulus interval
      (ISI, less than 10 ms) using an integrative computer system in 10 healthy
      subjects (age, 27-38 years). METHODS: The SEP and nerve action potentials were
      recorded at P3 with a reference of Fz in the International 10-20 System and the
      ipsilateral Erb's point, respectively. Double stimulation of the right median
      nerve with an ISI from 0.5 to 100 ms was performed to analyze the N20 and P30
      components at less than 10 ms. RESULTS: The P30 component was recognized
      following the second stimulation at an ISI of over 1 ms, while N20 was not
      identified at an ISI of less than 9 ms. There appeared a sub-component of SEP at
      1-12 ms ISI, which was not identified following a single stimulation under
      control conditions. CONCLUSIONS: The results indicated that the recovery function
      of given SEP components was not simply determined by the number of synapses
      interposed between the stimulus site and the generator source of the response in
      the central nervous system, but there might be a structural or functional process
      of low-cut filtering in the primary sensory cortex. We also considered that the
      final SEP waveform determined by the excitatory and inhibitory balance of the
      components, which could be changed with ISI, and that the existence of the sub
      component might cause the complexity of the recovery curve and large inter
      individual difference of the waveform.

PMID- 11955999
TI  - The correlation between physiological and psychological responses to odour
      stimulation in human subjects.
AB  - OBJECTIVES: To correlate physiological and psychological responses to odour
      stimulation. METHODS: Olfactory event-related potentials (OERP) were recorded
      from human subjects in response to different odour pulse protocols. Pulse
      duration and interstimulus interval (ISI) were varied while the subjects recorded
      pulse detection by a button press. RESULTS: There was a correlation between odour
      strength and OERP. The amplitude of the OERP (peak positive-peak negative)
      declined by 48% with repetitive stimulation for all stimulus strengths. The time
      constant for this decline (adaptation) was concentration dependent and varied
      from 10 to 4 s for increasing odorant strength (from 35 to 200 ms pulse of
      saturated amyl acetate vapour diluted 1:3 at 3 l min(-1) at 24 degrees C). The
      psychometric test score (cognitive odour perception) was also concentration
      dependent and increased with increasing stimulus strength at all ISIs except the
      lowest value; 2.5 s. At this ISI adaptation/habituation interfered with the dose
      response. The decline of the psychometric test score with increasing stimulus
      frequency (decreasing ISI) was more rapid (tau approximately 2.5 s) than that of
      the OERP. The psychometric test score declined to zero at a constant rate and was
      not dependent upon stimulus strength. CONCLUSIONS: Continuous olfactory
      stimulation results in a shut-down of cognitive perception with a time constant
      of around 2.5 s while the response of the physiological system (receptors,
      transduction and relay system) declines by about 50% with a slower time course (>
      or = 4 s). This former process defines habituation in the olfactory system while
      the latter describes adaptation. Since the adaptation process is concentration
      dependent the rate of adaptation contains information about odour strength, thus
      both the amplitude of the OERP and the rate of adaptation could encode stimulus
      strength.

PMID- 11956000
TI  - Agrypnia Excitata: a generalized overactivity syndrome and a useful concept in
      the neurophysiopathology of sleep.
AB  - OBJECTIVES: To analyse the clinicophysiological features of delirium tremens
      (DT), Morvan's fibrillary chorea (MC) and fatal familial insomnia (FFI) as
      representative of the new concept of Agrypnia Excitata (AE). METHODS: DT, MC and
      FFI were compared for their clinical and polysomnographic features and, for MC
      and FFI, post-mortem verification. RESULTS: DT, MC and FFI all display profound
      loss of slow-wave sleep (SWS) and abnormal rapid eye movement (REM) sleep with
      lack of muscular atonia and enacted dreams. Sleep spindles and K complexes are
      severely reduced. Motor overactivity is associated with increased sympathergic
      functions. Neuropathology discloses severe loss of neurons in the thalami and
      cingular areas in FFI, and leakage of antibodies in the thalamus in MC.
      CONCLUSIONS: Based on the similarities in DT, MC and FFI, we propose the new
      concept of AE as a clinical condition characterized by loss of SWS and abnormal
      REM sleep, associated with motor and autonomic sympathergic activation. AE is due
      to dysfunction of the thalamo-limbic system. Moreover, the preservation of light
      sleep in the face of severe loss of deep sleep in AE argues that 3 rather than
      the usually considered two (non REM and REM) independent states of sleep exist.

PMID- 11956001
TI  - Cortical EEG topography of REM onset: the posterior dominance of middle and high
      frequencies.
AB  - OBJECTIVES: To investigate the brain topography of human sleep
      electroencephalography (EEG) along the antero-posterior axis during rapid eye
      movement sleep (REM) onset and REM offset, by means of a quantitative analysis of
      EEG changes. METHODS: EEG power values were calculated across a 1.00-25.75 Hz
      frequency range during time intervals preceding and following REM onset of the
      first 4 sleep cycles of 10 normal subjects. Topographical changes were assessed
      through Fpz-A1, Fz-A1, Cz-A1, Pz-A1, Oz-A1 recordings during NREM-REM-NREM
      transitions. RESULTS: The temporal dynamics of REM onset is characterized by a
      specific topographical pattern of EEG changes with a relatively higher EEG
      activity at posterior sites: Oz does not show any clear change within the alpha
      and beta frequencies, at variance with the marked reductions of the other sites,
      while it shows reductions of power in the delta/theta and sigma frequency ranges
      of smaller size as compared to the other sites. REM offset does not appear as a
      mirror-image of REM onset, since the pattern of regional differences
      characterizing the NREM sleep preceding REM onset is not fully reached.
      CONCLUSIONS: REM onset is characterized by a general change of EEG activity
      toward a relative occipital diffusion of power, specifically distinguished by a
      posterior dominance of middle and high frequencies.

PMID- 11956002
TI  - A new design of a polysomnography-based multi-center treatment study for the
      restless legs syndrome.
AB  - Periodic limb movements (PLM) cause sleep disorders and daytime symptoms and are
      frequently associated with restless legs syndrome (RLS). Treatment of RLS with
      increased PLM during sleep (PLMS) has been evaluated in studies limited in size,
      methodology and study length. This long-term, placebo-controlled, multi-center,
      study with polysomnography (PSG) recordings has been designed in order to assess
      efficacy and safety parameters of pergolide treatment in RLS. This novel approach
      for a study was created to assure consistently high quality of sleep recording
      and analysis. Using defined criteria, 21 sleep centers were approved for the
      study after a pilot phase. Seventeen centers with 16 different PSG systems
      randomized 100 patients. Digital sleep recordings from 4 visits (baseline, 6
      weeks, 6 months, 1 year) were submitted to one central evaluation center
      following previously defined standardized operating procedures. Visual scoring of
      all recordings was performed by one independent scorer. Reliability of scoring
      was evaluated for 20 randomly selected baseline recordings. The mean epoch by
      epoch agreement for sleep stages was 88% (range 81-96%), mean arousal re-scoring
      differed by 0.5 (range: -16 to 20), and mean PLM index re-scoring differed by 0.1
      (range: -1.5 to 2.1). Using one scorer with a demonstrated high reliability in
      PSG scoring for all sleep recordings was very effective in terms of study cost,
      study duration, and data quality.

PMID- 11956003
TI  - EEG coherence in attention-deficit/hyperactivity disorder: a comparative study of
      two DSM-IV types.
AB  - OBJECTIVES: This study investigated differences in intrahemispheric and
      interhemispheric electroencephalographic (EEG) coherences between attention
      deficit/hyperactivity disorder (ADHD) and control children, and between children
      with the Combined (ADHDcom) and Inattentive (ADHDin) types of ADHD. METHODS:
      Three age- and sex-matched groups of 40 children, aged 8-12 years, diagnosed with
      ADHDcom, ADHDin, and normal control children, participated in this study. EEG was
      recorded from 21 sites during an eyes-closed resting condition and Fourier
      transformed. Wave-shape coherence was calculated for 8 intrahemispheric electrode
      pairs (4 in each hemisphere), and 8 interhemispheric electrode pairs, within each
      of the delta, theta, alpha and beta bands. RESULTS: At shorter inter-electrode
      distances, ADHD children had elevated intrahemispheric coherences in the theta
      band and reduced lateral differences in the theta and alpha bands. At longer
      inter-electrode distances, ADHD children had lower intrahemispheric alpha
      coherences than controls. Frontally, ADHD children had interhemispheric
      coherences elevated in the delta and theta bands, and reduced in the alpha band.
      An alpha coherence reduction in temporal regions, and a theta coherence
      enhancement in central/parietal/occipital regions, were also apparent. ADHDcom
      had greater intrahemispheric theta and beta coherences than ADHDin. Frontally,
      ADHDcom had higher levels of interhemispheric coherences than ADHDin for the
      delta and theta bands. In central/parietal/occipital regions, beta coherences
      were elevated in ADHDcom. CONCLUSIONS: EEG coherences suggest reduced cortical
      differentiation and specialisation in ADHD, particularly in cortico-cortical
      circuits involving theta activity. Generally, ADHDcom children displayed greater
      anomalies than ADHDin children.

PMID- 11956004
TI  - Picrotoxin-induced generalised convulsive seizure in rat: changes in regional
      distribution and frequency of the power of electroencephalogram rhythms.
AB  - OBJECTIVES: It is unknown how generalised discharges in primary generalised
      epilepsy (PGE) develop from background brain electrical activity or how
      widespread these discharged are throughout the brain. Here we address this by
      determining which neural structures and rhythms lead to and participate in
      generalised discharges in the picrotoxin rat model of PGE. METHODS: Rats with
      chronically implanted electrodes were infused with picrotoxin until a seizure
      occurred. This process we refer to as acute epileptogenesis. The
      electroencephalogram (EEG) was recorded and spectral analysis applied off-line to
      determine changes in the spectral power of contributing frequencies in 13 brain
      regions. RESULTS: Two types of generalised discharge occurred, spindles and
      seizure, which were present in all brain regions studied. None of the frequencies
      (1-100 Hz) were significantly increased in background EEG before either spindles
      or seizure. Within the generalised discharges, power changes revealed significant
      increases in 6-8 Hz, most powerful in ventrolateral thalamus and neocortex. Gamma
      frequencies were increased significantly in neocortical structures during
      spindles with further increases in most structures at seizure onset. 1 Hz was
      significantly increased in parietal cortex during spindles with differential
      increases at seizure onset. CONCLUSIONS: We conclude that gamma, 1 and 6-8 Hz
      frequencies do not appear to contribute to picrotoxin epileptogenesis but do play
      a role in generalised seizures. The distribution of these frequencies during
      discharges suggests that the spindles are thalamocortical events and that the
      seizure is a cortical event with downstream effects on other brain regions.

PMID- 11956005
TI  - Cortical silent period in two patients with meningioma and preoperative seizures:
      a pre- and postsurgical follow-up study.
AB  - OBJECTIVES: Prolongation of the cortical silent period (CSP) following
      transcranial magnetic stimulation has been reported in patients with partial
      epilepsy involving the primary motor cortex (M1). This study aimed to investigate
      the relationship between the expected intraindividual variations in risk factors
      for seizures and CSP duration. METHODS: We studied a 59-year-old woman with a
      rolandic meningioma and simple motor partial seizures and a 71-year-old woman
      with a parietal/occipital meningioma and complex partial seizures. Both patients
      had seizure as their initial symptom with complete postsurgical remission.
      Repeated pre- and postoperative CSP recordings were made from both first dorsal
      interosseous muscles. We compared the results to those obtained in 13 normals.
      RESULTS: In the patient with simple motor partial seizures, the CSP was
      significantly prolonged in preoperative recordings and 3 weeks after surgery.
      This CSP lengthening partly subsided 3 months after surgery. Finally, the CSP was
      normal 6, 8, and 18 months after surgery. In the patient with complex partial
      seizures, no CSP change was observed. CONCLUSIONS: In our patient with a rolandic
      meningioma, CSP prolongation was observed when the risk of seizure relapse was
      supposed to be higher (preoperative and early postoperative periods). This
      supports the view that CSP changes reflect compensatory mechanisms in M1
      epilepsy.

PMID- 11956006
TI  - EEG analysis with simulated neuronal cell models helps to detect pre-seizure
      changes.
AB  - OBJECTIVES: To test if a method for real-time detection of epileptic seizures
      based on electroencephalographic (EEG) analysis with simulated neuronal cell
      models can be modified to identify pre-seizure changes. METHODS: Our EEG analysis
      method consists of two simulated leaky integrate and fire units (LIFU) connected
      to a signal preprocessing stage that marks parts of the EEG signals with slopes
      larger than a preset threshold Hth with unit pulses. The LIFUs change their
      spiking frequency depending on the rate and the synchrony of the impinging pulse
      trains. Here, we use our method in a high-sensitivity mode by setting Hth to low
      values, which causes the LIFUs to continuously spike during the interictal state.
      We test if the LIFUs spiking rates change before seizure onset. RESULTS: We used
      9 long-term EEGs (16+/-7 h) of 7 patients with drug resistant epilepsy. Fifteen
      seizures were analyzed and all were preceded by an increase of the time-averaged
      spiking rates SR(av) of the LIFUs. We defined a function F(Sz), which quantifies
      the changes of SR(av). F(Sz) increased and stayed above an individually set and
      fixed threshold 83+/-91 min (range: 4-330 min) before EEG seizure onset. Only two
      false alarms occurred. CONCLUSIONS: We conclude that EEG analysis with simulated
      neuronal cell models may be used to detect pre-seizure changes with high
      sensitivity and specificity.

PMID- 11956009
TI  - Gp96: Swiss-army knife or tollgate?

PMID- 11956008
TI  - DC-T-cell synapses.

PMID- 11956007
TI  - Clinical, electrophysiological and immunological remissions after thymectomy in
      myasthenia gravis.
AB  - OBJECTIVES: Approximately 50% of patients treated with thymectomy have a chance
      for symptom-free life. However, immunological and neurophysiological
      abnormalities may be detected in patients with clinical remission. Although
      improvement usually parallels decrease in acetylcholine receptor antibody
      (AChRAb) levels and jitter values, there is a question what factors influence
      immunological and electrophysiological remission in a population of myasthenia
      gravis (MG) patients. METHODS: We analyzed retrospectively clinical data of 32 MG
      patients operated for generalized MG, followed-up at our department for 17.2 (4
      31) years. They were in clinical remission for 12.8 (2-25) years. All of them had
      single fiber electromyograhy (SFEMG) of extensor digitorum communis muscle (EDC)
      muscle and estimation of AChRAb level at the end of follow-up. Their age at onset
      of MG was 17 years (6-48) and at thymectomy 19 (6.4-58) years. Tensilon test was
      positive in 30, repetitive nerve stimulation in 29 cases. RESULTS: Clinical
      remission was reached on average 4.2 years after thymectomy. SFEMG jitter value
      normalized in 60% of cases. AChRAb were negative only in 34% of patients. Jitter
      values correlated with AChRAb levels (P=0.006, r=0.5) but were not related to
      clinical factors. Only time to thymectomy correlated with time from thymectomy to
      clinical remission (P=0.001, r=0.5). CONCLUSIONS: Clinical remission is not
      always accompanied by normalization of SFEMG and AChRAb. Although normalization
      of neuromuscular transmission in patients with remission of MG is individual,
      short duration of MG before thymectomy increases the chance of early remission.

PMID- 11956010
TI  - Breaking the kinetic window of T-cell activation.

PMID- 11956012
TI  - Dendritic cells and immune responses in the central nervous system.

PMID- 11956013
TI  - Dendritic cells unveiled.

PMID- 11956014
TI  - Glimpses of autoimmunity.

PMID- 11956015
TI  - Retroviral reviews.

PMID- 11956016
TI  - Viral and cellular interleukin-10 (IL-10)-related cytokines: from structures to
      functions.
AB  - The anti-inflammatory and immunosuppressive activities of IL-10 have been
      extensively studied during the last 10 years. More recently a series of new
      cytokines, structurally related to IL-10, were described. This family includes
      mda-7, IL-19, IL-20, IL-TIF/IL-22, and AK155. Most of the biological functions of
      these cytokines remain to be unraveled but new data are coming out steadily.
      Although none of these "IL-10 homologs" mimics IL-10 activities, they are likely
      to be involved in inflammatory processes as well. mda-7, IL-19 and IL-20 form a
      subfamily within IL-10 homologs, based on conserved amino acid sequences, and on
      the use of shared receptor complexes. Functional studies have stressed the
      potential suppressing activity of mda-7 on tumor growth. As for IL-20, its
      overexpression in transgenic mice led to skin abnormalities, reminiscent of
      psoriatic lesions in humans. IL-TIF/IL-22 is a Th1 cytokine, and was shown to
      upregulate the acute phase reactant production by liver cells. Finally, for
      AK155, originally described as a gene induced upon T cell transformation by
      Herpes-virus saimiri, functional data are still lacking to determine its
      biological activities.

PMID- 11956017
TI  - Dendritic cells (DC) promote natural killer (NK) cell functions: dynamics of the
      human DC/NK cell cross talk.
AB  - Dendritic cells (DC) were originally found critical in the setting of cognate
      immune responses. We first demonstrated that DC can also induce mouse NK cell
      activation and NK cell dependent-antitumor effects in mice. Here we analyzed the
      dynamics between DC and NK cells in human in vitro model systems. In the absence
      of LPS, DC do not trigger resting NK cells. Conversely, in the presence of LPS,
      resting bulk NK cells interacting with DC acquire CD25 and CD69 surface
      expression, produce high levels of IFN-gamma and lyse DAUDI cells. On activated
      IL-2 dependent NK cell lines, regardless of their differentiation stage, DC
      maintain or enhance NK cell proliferation and effector functions in the absence
      of exogenous cytokines. While IL-12, IL-15 and IL-18 are not critical, a direct
      cell-to-cell contact is mandatory for NK activation by DC and required for
      optimal proliferation. These data imply that DC also modulate human NK cell
      innate effector functions.

PMID- 11956018
TI  - Altered dendritic cells (DC) might be responsible for regulatory T cell imbalance
      and autoimmunity in nonobese diabetic (NOD) mice.
AB  - Nonobese diabetic (NOD) mice spontaneously develop diabetes, an auto-immune
      disease characterized by the destruction of insulin-secreting beta-cells by
      autoreactive T cells. Defects in development and/or functions of dendritic cells
      (DC) might be critical in eliciting the auto-immune reaction to beta cells in
      this model. In this paper, DC differentiation in NOD mice was investigated in
      vitro using bone marrow-derived progenitors (BM-DC) in the presence of GM-CSF and
      IL-4 or spleen-derived progenitors in the presence of GM-CSF and early acting
      cytokines such as Flt-3L and IL-6 (SPL-DC). In both culture systems, the absolute
      number of NOD DC generated was strongly reduced as compared to control strains.
      In addition, both BM-DC and SPL-DC from NOD mice show defective differentiation
      into mature DC in conventional culture conditions as indicated by low expression
      of MHC class II and CD80 molecules among CD11c positive cells and low capacity to
      stimulate allogeneic T cells. However, DC achieved full maturation when exposed
      to LPS, except for MHC class II expression that remained decreased. Ex vivo
      analysis confirmed an unusual phenotype of NOD DC. Both sets of results are thus
      consistent with a specific defect of DC maturation in these mice.

PMID- 11956019
TI  - Estradiol and raloxifene decrease the formation of multinucleate cells in human
      bone marrow cultures.
AB  - Estrogen (E2) deficiency is responsible for increased bone turnover in the
      postmenopausal period, and it can be prevented by estrogen replacement therapy.
      The way estrogen acts on bone cells is not fully understood. Human bone marrow
      cell cultures may be a reliable model for studying the action of steroids on
      osteoclastogenesis in vitro. We examine the effects of estradiol and Raloxifene,
      a selective estrogen receptor modulator, on human primary bone marrow cells
      cultured for 15 days. 17beta-estradiol and Raloxifene significantly decreased the
      number of tartrate-resistant acid phosphatase multinucleate cells from osteoclast
      precursors on day 15. Estrogen receptor alpha (ER-alpha) mRNA was present in bone
      marrow mononuclear cells cultured for 5 days, but there was no estrogen receptor
      beta (ER-beta) mRNA, suggesting that this effect was mediated by ER-alpha. 15-day
      cultures no longer contained ER-alpha mRNA, suggesting that estrogen acts on
      early events of osteoclast differentiation. Finally, 10-8 M 17beta-estradiol has
      no effect on the release of IL-6 and IL-6-sr into the medium of marrow
      mononuclear cells cultured for 5 or 15 days. Osteoclast apoptosis was not
      affected by estradiol or Raloxifene after 15 days of culture under our
      conditions. In conclusion, we have shown that both estradiol and Raloxifene
      inhibit osteoclast differentiation in human bone marrow mononuclear cultures. The
      biological effect that can mimic in vivo differentiation could be mediated
      through ER-alpha.

PMID- 11956020
TI  - Interleukin-10 and cAMP-elevating agents cooperate to induce suppressor of
      cytokine signaling-3 via a protein kinase A-independent signal.
AB  - We have recently shown that IL-10 represents an efficient stimulus for suppressor
      of cytokine signalling (SOCS)-3 mRNA expression in human neutrophils and PBMC.
      Herein, we identify cAMP-elevating agents such as prostaglandin E2 (PGE2), PGE1,
      forskolin, dibutyryl cAMP (dbcAMP) and cholera toxin as a novel class of agonists
      able to induce SOCS-3 mRNA and protein expression in human leukocytes,
      cooperating with interleukin-10 (IL-10) in such activities. While PGE2 or dbcAMP
      prolonged the stability of SOCS-3 mRNA isolated from IL-10-treated leukocytes,
      inhibitors of cAMP-dependent protein kinase A (H89, KT5720, and St-Ht31 peptide)
      did not influence the action of PGE2/dbcAMP and/or IL-10 on SOCS-3 mRNA and
      protein expression, implying that their effect are mediated through a PKA
      independent pathway. Taken together, our data identify cAMP-elevating substances
      as a novel class of agonists able to trigger SOCS-3 expression, and suggest that
      SOCS-3 might be involved in the regulatory effects of cAMP-elevating substances.

PMID- 11956022
TI  - The combination of the interleukin-1alpha (IL-1alpha-889) genotype and the
      interleukin-10 (IL-10 ATA) haplotype is associated with increased interleukin-10
      (IL-10) plasma levels in healthy individuals.
AB  - Family studies have demonstrated striking differences between individuals in
      their ability to produce IL-10 following lipopolysaccharide (LPS) stimulation of
      whole blood cultures in vitro, suggesting that differences in IL-10 production
      involve a considerable hereditary component. The first aim of this study was to
      analyse the possible effect of IL-10 genotypes and haplotypes on IL-10 plasma
      levels in a healthy Finnish population. As previous reports have demonstrated
      that endogenously produced IL-1 induces LPS-stimulated IL-10 production and that
      IL-10 inhibits synthesis of IL-1 in human monocytes, it is apparent that these
      two cytokines form an autoregulatory feedback loop. Secondly, we were interested
      whether any relationship could be found between IL-10 and IL-1beta in vivo. To
      examine this, the influence of IL-1alpha -889, IL-1beta -511 and IL-1Ra VNTR
      genotypes and IL-10 genotypes/haplotypes (ACC, GCC and ATA) on IL-10 plasma
      levels, and a putative correlation between IL-10 and IL-1alpha plasma levels were
      analysed. Four hundred adult blood samples were obtained from the Finnish Red
      Cross Blood Transfusion Centre, Tampere. The IL-10, IL-1alpha, IL-1beta and IL
      1Ra gene polymorphisms were analysed using PCR. IL-1beta and IL-10 plasma levels
      were measured using an ELISA method. Our results indicated that increased IL-10
      plasma levels were associated with the ATA haplotype (p = 0.03) and,
      surprisingly, with the IL-1alpha allele 2 carrier status (p = 0.02) in healthy
      individuals. This IL-1alpha 2+/ATA+ combination was found in 93 subjects out of
      400 analysed (23%) and was associated with significantly high IL-10 plasma levels
      (p = 0.002). When individuals were classified into three groups, with no
      detectable IL-10 plasma levels (n = 145), with moderate levels (n = 152) and with
      high levels (n = 100) of IL-10, the IL-1alpha2+/ATA+ combination was more likely
      present among those with high levels than among those with undetectable levels of
      IL-10 (OR = 3.3, 95% CI 1.8 - 6.0, p < 0.001) or those with moderate levels of IL
      10 (OR = 2.0, 95% CI 1.2 - 3.6, p = 0.012). Besides the observed association
      between IL-1alpha genotype and IL-10 levels, a moderate correlation was found
      between IL-10 and IL-1beta levels (r = 0.6, p = 0.01) among IL-10 producers (n =
      252). The present findings suggest that the genotype combination of IL-1alpha
      2+/ATA+ has a regulatory effect on basal IL-10 levels and that among individuals
      with measurable IL-10 plasma levels, IL-1beta and IL-10 basal levels correlate.
      Until now, data on the feedback loop between IL-1 and IL-10 cytokines have been
      based on studies in vitro, but now our results suggest that this relationship may
      also exist in vivo.

PMID- 11956021
TI  - Different patterns of interleukin-1alpha and interleukin-1beta expression in
      organs of normal young and old mice.
AB  - The different physiological roles of interleukin-1alpha (IL-1alpha) and
      interleukin-1beta (IL-1beta) are not well understood, especially when considering
      the apparent overlap and redundancy of the two IL-1 molecules. Characterization
      of IL-1alpha and IL-1beta expression was performed in this study in organs from
      young and old mice, using immunohistochemistry and ELISA (enzyme-linked
      immunosorbent assay). The results indicate that organ IL-1alpha and IL-1beta
      display different patterns of expression: IL-1alpha is manifested more
      prominently in lymphoreticular organs (lungs, small intestine, spleen, liver),
      while IL-1beta is more evident in highly specialized and more vulnerable organs,
      which do not play a leading role in defense against infections and intoxication
      (heart, brain, skeletal muscle, kidney). This differential expression is more
      accentuated in old mice, possibly pointing to the special relevance of these
      cytokines to organ homeostasis in old age. These findings may shed new light on
      the physiological functions of IL-1alpha and IL-1beta, and may also lead to the
      development of improved therapeutic approaches, based on the specific
      manipulation of these cytokines.

PMID- 11956023
TI  - The interleukin-6 G(-174)C polymorphism and the ex vivo interleukin-6 response to
      endotoxin in severely injured blunt trauma patients.
AB  - The aim of this study was to evaluate whether the -174 G/C promoter polymorphism
      of the interleukin-6 (IL-6) gene is associated with the ex vivo, whole blood IL-6
      response to endotoxin with the development of severe sepsis in severely injured,
      blunt trauma patients. Patients with a severe trauma and an injury severity score
      of 16 were included in the study. The IL-6 -174 G/C promoter polymorphism was
      determined by real-time polymerase chain reaction (PCR) assay using specific
      fluorescence-labelled hybridisation probes. Whole blood of the patients was
      stimulated with endotoxin and the IL-6 concentrations were measured by ELISA.
      There was no association between the IL-6 -174 genotypes and the ex vivo,
      stimulated IL-6 response: 25% of the patients developed severe sepsis later in
      the clinical course. These patients had higher IL-6 concentrations following
      whole blood stimulation on day 1 (p = 0.046) after the trauma than patients with
      uncomplicated post-traumatic recovery. The difference was even more significant
      on day 2 after the trauma (p = 0.02). High IL-6 responses in a whole blood
      stimulation assay with endotoxin on days 1 and 2 after a trauma are associated
      with severe post-traumatic sepsis. Genotyping for the IL-6 -174 G/C polymorphism
      does not allow early identification of trauma patients with a high, ex vivo IL-6
      synthesis capacity.

PMID- 11956024
TI  - Comparison of leptin- and interleukin-6-regulated expression of the rPAP gene
      family: evidence for differential co-regulatory signals.
AB  - The pancreatitis-associated protein (PAP)/regenerating protein (REG) family
      represents a complex group of small secretory proteins, which can function as
      acute phase reactants, lectins, antiapoptotic factors or growth factors for
      pancreatic beta-cells and neural cells. Transcriptional induction of rPAP/Reg
      genes was studied here in PC12 cells made responsive to leptin. Northern-blots
      showed quantitative differences in induction of four major family members by
      leptin and IL-6. Surprisingly, induction by leptin was strongly enhanced upon
      forskolin co-treatment whereas induction by IL-6 was counteracted. Functional
      studies involving progressive rPAP I promoter deletions showed, in the case of
      leptin, a clear correlation with predicted cis-regulatory elements. Leptin
      induced stimulation was dependent on STAT3, since over-expression of dominant
      negative STAT3, but not of dominant-negative STAT1, completely blocked
      transcriptional activation. In case of IL-6, an enhancer element outside the
      cloned promoter fragment is required for full stimulation. The effects of
      forskolin in a leptin and IL-6 context could not be explained at the promoter
      level, but rather events occurring upstream in the signalling cascade must be
      postulated to explain the differential co-regulatory effects.

PMID- 11956026
TI  - Tumor necrosis factor-alpha mRNA stability in human peripheral blood cells after
      lipopolysaccharide stimulation.
AB  - TNF synthesis depends on many controls at transcriptional and post
      transcriptional levels, including in particular mRNA stability and translational
      efficiency through the AU-rich elements (ARE) in the 3'untranslated region
      (3'UTR) of mRNA. We have previously reported that upon lipopolysaccharide (LPS)
      stimulation, TNF protein secreted by normal peripheral blood cells (PBC) from non
      Hodgkin's lymphoma patients was slightly, but not significantly increased when
      compared to healthy control donors. In contrast, the relative amounts of TNF mRNA
      were significantly higher in lymphoma patients. Thus, the implication of TNF mRNA
      stability has been explored by investigating the decay rate of LPS-induced TNF
      mRNA and the expression of tristetraprolin (TTP), one of the factors involved in
      the destabilization of TNF mRNA. After LPS incubation, peak levels of TTP mRNA
      preceded those of TNF mRNA, supporting its implication in the control of TNF mRNA
      levels in human PBC. Furthermore, similar TTP expression in both groups
      correlated with an identical decay rate of TNF mRNA, which excludes this pathway
      for the higher LPS-induced TNF mRNA levels in PBC from lymphoma patients.

PMID- 11956025
TI  - Mice lacking alpha(2)-macroglobulin show an increased host defense against Gram
      negative bacterial sepsis, but are more susceptible to endotoxic shock.
AB  - The onset of an acute phase response is one of the initial steps in the defense
      against an infectious organism. Alpha(2)-macroglobulin (alpha(2)M), an acute
      phase protein in most mammalian species, is known to have a broad antiprotease
      activity, but it can also bind a number of growth factors, cytokines, ions and
      lipid factors. We have shown that alpha(2)M-deficient (MAM-/-) mice are more
      resistant to a lethal Gram-negative infection compared to control mice. This
      increased resistance was reflected in significantly higher body temperatures,
      compared to control mice, during the infection as well as in a prolonged and
      increased survival. Moreover, the clearance of bacteria in MAM-/- mice was
      significantly more efficient than in control mice. On the other hand, MAM-/- mice
      were more susceptible to endotoxin. An LD(100) challenge with endotoxin in MAM-/-
      mice was not lethal for control mice. Our data suggest that alpha(2)M plays a
      dual role during an acute phase response. In the establishment of a lethal Gram
      negative infection, leading to sepsis and septic shock, it has a mediating role
      by hampering the efficient clearance of bacteria. During endotoxic shock,
      however, alpha(2)M has a rather protective function.

PMID- 11956027
TI  - Caspase-1 levels in biological fluids from patients with multiple sclerosis and
      from patients with other neurological and non-neurological diseases.
AB  - In multiple sclerosis (MS), pathological white matter damage in the central
      nervous system is sustained by immune-inflammatory response. Caspase-1 plays a
      pivotal role in immune-mediated inflammation, as it regulates the cellular export
      of IL-1beta and IL-18. We carried out a preliminary in vitro study of the
      kinetics of extracellular caspase-1 release. We then measured caspase-1 levels in
      paired serum and cerebrospinal fluid (CSF) samples of 75 MS patients, 15 healthy
      subjects, and patients with other neurological diseases. Paired synovial fluid
      and serum samples of patients with juvenile idiopathic arthritis, and paired
      sputum and serum samples of asthma patients were also studied. Mean serum caspase
      1 concentrations did not differ between groups. Caspase-1 was detected in the CSF
      of patients with acute, but not stable, MS [7.5 +/- (SEM) 0.9 pg/ml; test's
      sensitivity, 56% and specificity, 100%]. Its levels correlated with pleocytosis.
      The highest mean caspase-1 levels were found in the arthritic synovial fluids
      (945.5 +/- 126.6 pg/ml, which correlated with erythrocyte sedimentation rate),
      and in the sputum samples (370.1 +/- 71.0 pg/ml, which correlated with the number
      of macrophages in the sputum). On condition that caspase-1 is determined in the
      fluids pertaining to the disease-specific inflammatory sites, its level is a
      reliable marker of ongoing immune-inflammatory response. The enzyme measurement
      in CSF can also help define state-trait in MS.

PMID- 11956028
TI  - Divergent effects of tumor necrosis factor-alpha and lymphotoxin-alpha on lethal
      endotoxemia and infection with live Salmonella typhimurium in mice.
AB  - During septic shock with Gram-negative microorganisms, mortality is determined by
      two independent factors: high concentrations of circulating proinflammatory
      cytokines and multiplication of the microorganisms in the organs of the host. We
      studied the role of endogenous tumor necrosis factor-alpha (TNF) and lymphotoxin
      alpha (LT) in the pathogenesis of lethal endotoxemia and infection with viable
      Salmonella typhimurium. Compared to wild-type control mice, TNF-/-LT-/- knock-out
      mice were more resistant (100% versus 25% mortality) to a lethal challenge with
      LPS, due to a significantly decreased production of the proinflammatory cytokines
      TNF, IL-1alpha and IL-1beta. In contrast, TNF-/-LT-/- mice were highly
      susceptible to infection with viable S. typhimurium as compared to wild-type mice
      (100% versus 0% mortality), and this was accompanied by a 100-fold greater
      bacterial load in their organs. The effect of endogenous TNF and LT during
      infection was mediated by a defective recruitment of neutrophils at the site of
      infection, as well as a reduced intracellular killing of S. typhimurium by these
      cells. These results show that TNF and LT have crucial, yet opposite effects on
      lethal endotoxemia induced by S. typhimurium LPS and on the infection of mice
      with live Salmonella microorganisms, and suggest caution when extrapolating
      results obtained in the lethal endotoxemia model to bacteremia in patients.

PMID- 11956029
TI  - Th1/Th2 cytokine balance and nitric oxide in cerebrospinal fluid and serum from
      patients with multiple sclerosis.
AB  - Tumor necrosis factor (TNF-alpha) and IL-10 are key regulators of the T helper
      (Th)1/Th2 balance, which is critically skewed in many pathological conditions
      including immune-mediated inflammatory diseases of central nervous system (CNS)
      such as multiple sclerosis (MS). Nitric oxide (NO) has been reported to have dual
      effects on CNS pathology, and to play an important role in MS. We performed a
      cross-sectional study in 17 randomly selected patients during MS flare-up, and
      compared levels of TNF-alpha, IL-10 and NO in serum and cerebrospinal fluid (CSF)
      with the serum values of these mediators in two different control groups, healthy
      subjects and HIV-infected untreated patients. Serum and CSF values of TNF-alpha,
      IL-10 and NO were higher in MS patients than in the serum of healthy controls.
      Two MS patients showed increased levels of NO in CSF, with inversion of the
      NO(SERUM)/NO(CSF) quotient, which is clearly indicative of an intrathecal
      production of NO. No correlation among the values of both cytokines and NO, and
      the laboratory parameters analysed in MS patients (IgG index, presence of IgG
      oligoclonal bands and albumin quotient) was found. The high levels of TNF-alpha
      and IL-10 (both in serum and CSF) accompanying an MS attack suggest a
      simultaneous expression of Th1 and Th2 cytokines as opposed to sequential
      expression of Th1 followed by Th2 as described in the models of experimental
      autoimmune encephalomyelitis (EAE). Globally, our results support the inherent
      heterogeneity of the disease.

PMID- 11956030
TI  - Retinoids, cisplatin and interferon-alpha in recurrent or metastatic cervical
      squamous cell carcinoma: clinical results of 2 phase II trials.
AB  - BACKGROUND: There is no standard treatment for inoperable recurrent or metastatic
      cancer of the uterine cervix. Retinoids and interferon, in combination with
      cytotoxic compounds, have been shown to be active in squamous cell carcinoma
      (SCC). This phase II trial sought to estimate the response rate and the tolerance
      to a 3-month treatment combining cisplatin, interferon-alpha (IFN-alpha) and all
      trans-retinoic (tRA) or 13 cis retinoic acid (13Cis), in women with recurrent or
      metastatic cervical SCC. PATIENTS AND METHODS: Between November 1994 and October
      1996, 33 patients, who had previously received aggressive treatment, and with
      metastatic and/or bulky disease were enrolled: 22 received tRA(40 mg/m(2)/day),
      11 received 13Cis (1 mg/kg/day) in combination with IFN-alpha (6.106 UI/day SC)
      for 84 days plus cisplatin (40 mg/m(2)IV, days 1, 28 and 56). RESULTS: All
      patients were evaluable for response and/or toxicity. Toxicities were easily
      manageable and were never life-threatening, with major grade 3/4 vomiting (54%)
      and asthenia (54%). Seventeen patients (52%) stopped or reduced treatment because
      of toxicity or progression. Six objective responses (18%) were observed. No
      complete response was recorded. Median response duration was 4 months. Time to
      progression was 9 months [range 3.3 to 20.9] for responders and 7 months [range
      1.7 to 32] for all patients. CONCLUSIONS: Regarding toxicity, this regimen should
      no longer be recommended in previously treated, advanced uterine SCC. However,
      the consistent response rate reported here may warrant further investigations in
      an early setting. Retinoid-based treatment with cytokines remains a promising
      field of research.

PMID- 11956031
TI  - Circulating macrophage colony stimulating factor as a marker of tumour
      progression.
AB  - Tumour expression of the macrophage colony stimulating factor (CSF-1 or MCSF) has
      been associated with an adverse prognosis in breast cancer, through an effect on
      the promotion of metastasis. The aim of the present study was to evaluate the
      clinical relevance of high circulating CSF-1 levels in patients with newly
      diagnosed breast tumours and correlate CSF-1 with clinico-pathological
      parameters. A secondary aim was to also measure CSF-1 in patients with other
      tumour types and at different stages of disease. Using a commercially available
      ELISA, pre-treatment plasma levels of CSF-1 were assessed, in 471 consecutive
      patients diagnosed with breast tumours, in 70 patients with newly diagnosed
      cancer of the head & neck, in 32 men with prostate cancer metastatic to bone and
      in 39 women with advanced metastatic breast cancer. Mean CSF-1 levels were
      significantly higher in patients with locally advanced (p <.015) or metastatic
      breast tumours (p <.048) and in a group of primary breast cancer patients (n =
      26) selected for intensive chemotherapy because of multiple adverse tumour
      characteristics (p <.0002). Mean CSF-1 was also higher in patients younger than
      35 years (p <.02) and in post-menopausal patients (p <.03). There was no
      significant association with tumour histologic type, grade, or other individual
      histopathologic parameters. No significant association was found between pre
      treatment CSF-1 and overall/relapse free survival. Median CSF-1 levels were
      dramatically higher in patients with newly diagnosed tumours of the head & neck
      (604 pg/ml), in men with prostate cancer metastatic to bone (627 pg/ml) and women
      with advanced metastatic breast cancer (867 pg/ml) than those seen in patients
      with newly diagnosed breast tumours (334 pg/ml). Our data support the hypothesis
      that CSF-1 may play a functional role in tumour progression to metastasis as has
      previously been reported in animal models.

PMID- 11956032
TI  - The effect of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF
      alpha) on granulocyte macrophage-colony stimulating factor (GM-CSF) production by
      neuronal precursor cells.
AB  - AIMS: To determine whether granulocyte macrophage-colony stimulating factor (GM
      CSF) production by neuronal precursor (NT2) cells can be regulated by IL-1beta
      and TNF-alpha. BACKGROUND: We have previously demonstrated GM-CSF expression by
      neurons of the developing human brain, as well as by NT2 cells. IL-1beta and TNF
      alpha upregulate GM-CSF production in glial cells, but GM-CSF regulation in
      neurons is as yet undefined. We hypothesized that IL-1beta and TNF-alpha would
      increase GM-CSF mRNA and protein production in NT2 cells. METHODS: The effect of
      IL-1beta and TNF-alpha on GM-CSF production was assessed by dose response (0 to
      2,000 U/ml), and time course (0 to 48 hours incubation) experiments. GM-CSF mRNA
      and protein production were assessed by quantitative RT-PCR and by ELISA. The
      effect of these cytokines on cell turnover was determined by BrdU incorporation.
      RESULTS: IL-1beta increased GM-CSF mRNA and protein expression by NT2 cells. This
      effect was time and dose dependent, and the effective dose ranging from (20-200
      U/ml). TNF-alpha increased GM-CSF mRNA expression to a lesser extent than did IL
      1beta (maximal stimulation at 200 U/ml), and a minimal increase in net protein
      accumulation was noted. Neither cytokine increased NT2 cell turnover.
      CONCLUSIONS: IL-1beta and TNF-alpha both increase GM-CSF mRNA expression by NT2
      cells, but only IL-1beta increases net GM-CSF protein accumulation.

PMID- 11956034
TI  - Reliability of health information on the Internet: an examination of experts'
      ratings.
AB  - BACKGROUND: The use of medical experts in rating the content of health-related
      sites on the Internet has flourished in recent years. In this research, it has
      been common practice to use a single medical expert to rate the content of the
      Web sites. In many cases, the expert has rated the Internet health information as
      poor, and even potentially dangerous. However, one problem with this approach is
      that there is no guarantee that other medical experts will rate the sites in a
      similar manner. OBJECTIVES: The aim was to assess the reliability of medical
      experts' judgments of threads in an Internet newsgroup related to a common
      disease. A secondary aim was to show the limitations of commonly-used statistics
      for measuring reliability (eg, kappa). METHODS: The participants in this study
      were 5 medical doctors, who worked in a specialist unit dedicated to the
      treatment of the disease. They each rated the information contained in newsgroup
      threads using a 6-point scale designed by the experts themselves. Their ratings
      were analyzed for reliability using a number of statistics: Cohen's kappa, gamma,
      Kendall's W, and Cronbach's alpha. RESULTS: Reliability was absent for ratings of
      questions, and low for ratings of responses. The various measures of reliability
      used gave conflicting results. No measure produced high reliability. CONCLUSIONS:
      The medical experts showed a low agreement when rating the postings from the
      newsgroup. Hence, it is important to test inter-rater reliability in research
      assessing the accuracy and quality of health-related information on the Internet.
      A discussion of the different measures of agreement that could be used reveals
      that the choice of statistic can be problematic. It is therefore important to
      consider the assumptions underlying a measure of reliability before using it.
      Often, more than one measure will be needed for "triangulation" purposes.

PMID- 11956033
TI  - A framework for the evaluation of Internet-based diabetes management.
AB  - BACKGROUND: While still in its infancy, Internet-based diabetes management shows
      great promise for growth. However, the following aspects must be considered: what
      are the key metrics for the evaluation of a diabetes-management site? how should
      these sites grow in the future and what services should they offer? OBJECTIVES:
      The purpose of this paper is to examine the needs of the patient and the health
      care professional in an Internet-based diabetes-management solution and how these
      needs are translated into services offered. METHODS: An evaluation framework was
      constructed based on a literature review that identified the requirements for an
      Internet-based-diabetes-management solution. The requirements were grouped into 5
      categories: Monitoring, Information, Personalization, Communication, and
      Technology. Two of the market leaders (myDiabetes and LifeMasters) were selected
      and were evaluated with the framework. The Web sites were evaluated independently
      by 5 raters using the evaluation framework. All evaluations were performed from
      November 1, 2001 through December 15, 2001. RESULTS: The agreement level between
      raters ranged from 60% to 100%. The multi-rater reliability (kappa) was 0.75 for
      myDiabetes and 0.65 for LifeMasters, indicating substantial agreement. The
      results of the evaluations indicate that LifeMasters is a more-complete solution
      than myDiabetes in all dimensions except Information, where both sites were
      equivalent. LifeMasters satisfied 32 evaluation criteria while myDiabetes
      satisfied 24 evaluation criteria, out of a possible 40 in the framework.
      CONCLUSIONS: The framework is based on the recognition that the management of
      diabetes via the Internet is based on several integrated dimensions: Monitoring,
      Information, Personalization, Communication, and Technology. A successful
      diabetes-management system should efficiently integrate all dimensions. The
      evaluation found that LifeMasters is successful in integrating the health care
      professional in the management of diabetes and that MyDiabetes is quite effective
      in providing a communication channel for community creation (however,
      communication with the health care professional is lacking).

PMID- 11956035
TI  - Web-based cognitive behavior therapy: analysis of site usage and changes in
      depression and anxiety scores.
AB  - BACKGROUND: Cognitive behavior therapy is well recognized as an effective
      treatment and prevention for depression when delivered face-to-face, via self
      help books (bibliotherapy), and through computer administration. The public
      health impact of cognitive behavior therapy has been limited by cost and the lack
      of trained practitioners. We have developed a free Internet-based cognitive
      behavior therapy intervention (MoodGYM, http://moodgym.anu.edu.au) designed to
      treat and prevent depression in young people, available to all Internet users,
      and targeted to those who may have no formal contact with professional help
      services. OBJECTIVE: To document site usage, visitor characteristics, and changes
      in depression and anxiety symptoms among users of MoodGYM, a Web site delivering
      a cognitive-behavioral-based preventive intervention to the general public.
      METHODS: All visitors to the MoodGYM site over about 6 months were investigated,
      including 2909 registrants of whom 1503 had completed at least one online
      assessment. Outcomes for 71 university students enrolled in an Abnormal
      Psychology course who visited the site for educational training were included and
      examined separately. The main outcome measures were (1) site-usage measures
      including number of sessions, hits and average time on the server, and number of
      page views; (2) visitor characteristics including age, gender, and initial
      Goldberg self-report anxiety and depression scores; and (3) symptom change
      measures based on Goldberg anxiety and depression scores recorded on up to 5
      separate occasions. RESULTS: Over the first almost-6-month period of operation,
      the server recorded 817284 hits and 17646 separate sessions. Approximately 20% of
      sessions lasted more than 16 minutes. Registrants who completed at least one
      assessment reported initial symptoms of depression and anxiety that exceeded
      those found in population-based surveys and those characterizing a sample of
      University students. For the Web-based population, both anxiety and depression
      scores decreased significantly as individuals progressed through the modules.
      CONCLUSIONS Web sites are a practical and promising means of delivering cognitive
      behavioral interventions for preventing depression and anxiety to the general
      public. However, randomized controlled trials are required to establish the
      effectiveness of these interventions.

PMID- 11956036
TI  - The WWW of the World Wide Web: Who, What, and Why?

PMID- 11956038
TI  - Assessing respiratory control during spontaneous breathing: practice may be more
      difficult than theory.

PMID- 11956037
TI  - Survey of doctors' experience of patients using the Internet.
AB  - BACKGROUND: There have been many studies showing the variable quality of Internet
      health information and it has often been assumed that patients will blindly
      follow this and frequently come to harm. There have also been reports of problems
      for doctors and health services following patient Internet use, but their
      frequency has not been quantified. However, there have been no large, rigorous
      surveys of the perceptions of Internet-aware doctors about the actual benefits
      and harms to their patients of using the Internet. OBJECTIVE: To describe
      Internet-literate doctors' experiences of their patients' use of the Internet and
      resulting benefits and problems. METHODS: Online survey to a group of 800 Web
      using doctors (members of a UK medical Internet service provider, Medix) in
      September and October 2001. RESULTS: Responses were received from 748 (94%)
      doctors, including 375 general practitioners (50%). Respondents estimated that 1%
      2% of their patients used the Internet for health information in the past month
      with no regional variation. Over two thirds of the doctors considered Internet
      health information to be usually (20%) or sometimes (48%) reliable; this was
      higher in those recently qualified. Twice as many reported patients experiencing
      benefits (85%; 95% confidence interval, 80%-90%) than problems (44%; 95%
      confidence interval, 37%-50%) from the Internet. Patients gaining actual physical
      benefits from Internet use were reported by 40% of respondents, while 8% reported
      physical harm. Patients' overall experiences with the Internet were judged
      excellent 1%, good 29%, neutral 62%, poor 9%, or bad <1%. Turning to the impact
      of patient Internet use on the doctors themselves, 13% reported no problems, 38%
      1 problem, and 49% 2 or more problems. Conversely, 20% reported no benefits for
      themselves, 49% 1 benefit, and 21% 2 or more benefits. CONCLUSIONS: These doctors
      reported patient benefits from Internet use much more often than harms, but there
      were more problems than benefits for the doctors themselves. Reported estimates
      of patient Internet usage rates were low. Overall, this survey suggests that
      patients are deriving considerable benefits from using the Internet and that some
      of the claimed risks seem to have been exaggerated.

PMID- 11956040
TI  - Open mind, open airways: broadening the paradigm of prostaglandins and allergic
      airway inflammation.

PMID- 11956039
TI  - Stress and asthma: the plot thickens.

PMID- 11956041
TI  - Surgical aspects of esophageal disease: perforation and caustic injury.

PMID- 11956042
TI  - Influence of chemoreflexes on respiratory variability in healthy subjects.
AB  - The background of this study was the hypothesis that respiratory variability is
      influenced by chemoreflex regulation. In search for periodicities in the
      variability due to instability of the respiratory control system, spectral
      analysis was applied to breath-to-breath variables in 19 healthy subjects at
      rest. During room-air breathing, coherent oscillations in end-tidal CO2
      (PET(CO2)) and mean inspiratory flow (VI/TI) were found in 15 subjects with
      frequencies mostly below 0.15 cycles per breath. Coherent oscillations in
      PET(CO2) and VI/TI were expressed by gain (0.13 to 0.34 L/second small middle dot
      kPa) and phase (-170 degrees to +8 degrees ). The oscillations in VI/TI were in
      phase with inspiratory volume (VI). A model that describes the effects of
      chemoreflex feedback to noise in the system could explain these gains and phases,
      whereas a model without chemoreflex could not. During 100% O2 breathing, only
      eight subjects had coherent oscillations in PET(CO2) and VI/TI. The coherent
      oscillations in PET(CO2) and VI/TI were interpreted as a manifestation of
      chemoreflex activity. We conclude that respiratory variability is not a random
      process but contains information on chemoreflex properties, such as the
      chemoreflex gain. The analysis of respiratory variability therefore provides a
      new tool to study the action of the chemoreflexes without application of external
      stimuli.

PMID- 11956043
TI  - Altered autonomic function and reduced arousability in apparent life-threatening
      event infants with obstructive sleep apnea.
AB  - The aim of this study was to examine cardiorespiratory control in infants
      presenting with an apparent life-threatening event (ALTE). We performed six to
      eight 45 degrees head-up tilts in 10 ALTE infants (age, 14 +/- 3 weeks) and 12
      age-matched control subjects during slow wave sleep and rapid eye movement sleep
      (REM). All infants underwent full overnight polygraphic sleep recordings with
      noninvasive measurement of beat-to-beat blood pressure. All control infants had
      normal sleep breathing. In contrast, 5 of the 10 ALTE infants had more than two
      obstructive apneas per hour of sleep, with short hypoxic episodes (obstructive
      sleep apnea [OSA]). In slow wave sleep, in response to the tilt, the ALTE infants
      with OSA showed a reduced heart rate response, and three of the five showed a
      marked postural hypotension. The ALTE infants with OSA also had altered heart
      rate and blood pressure variability and an increased arousal threshold in REM (p
      = 0.0002). By contrast, those ALTE infants with normal sleep breathing had
      cardiovascular and arousal responses similar to those of the control infants. We
      conclude that a number of ALTE infants with OSA have abnormal cardiovascular
      autonomic control that, combined with their decreased arousability in REM, may
      provide an explanation for the ALTE episodes.

PMID- 11956044
TI  - Mechanical properties of the lung and upper airways in patients with sleep
      disordered breathing.
AB  - We studied the changes in lung and upper airway mechanics in adult human subjects
      with obstructive sleep apnea/hypopnea syndrome (OSAHS) during wakefulness, sleep,
      and at arousal from sleep. We used two numerical methods that we have previously
      developed specifically for dealing with inspiratory flow limitation during sleep:
      the modified Mead-Whittenberger method, and information-weighted histograms
      obtained using recursive least squares. Full polysomnography including esophageal
      pressure and airflow measurements was performed in seven men with OSAHS
      (respiratory disturbance index: 55.8 +/- 23.2 events/h). Pharyngeal pressure was
      recorded in four of the subjects to partition lung mechanics into its upper
      airway and lower lung components. Both techniques showed that total lung
      resistance and elastance increased significantly (p < 0.05) during obstructed
      breathing and that this increase was reversed at the end of the obstruction. The
      partitioning of mechanics showed that upper airway collapse was primarily
      responsible for the increase in lung resistance. Our results suggest that OSAHS
      may lead to transient abnormalities in the recruitment of lung units and the gas
      exchanging capacity of the lungs.

PMID- 11956045
TI  - School examinations enhance airway inflammation to antigen challenge.
AB  - Psychological stress can lead to asthma exacerbations in some patients. It is our
      hypothesis that the stress effect can occur through an enhancement of allergic
      inflammatory response. To investigate this possibility, airway antigen challenge
      was evaluated in 20 college students with mild asthma during both a low-stress
      phase (midsemester or two weeks postfinal examination) and a stress phase (final
      examination week). Subjects completed questionnaires to assess psychological
      state and underwent inhaled antigen challenge. Sputum samples were collected
      before challenge, and six and 24 hours and seven days postchallenge. Leukocytes
      were counted and eosinophil-derived neurotoxin (EDN) was measured in sputum
      supernates. Sputum cells were cultured and stimulated ex vivo with
      phytohemagglutinin (10 microg/ml), and culture supernates were assayed for
      interleukin-5 (IL-5) and interferon-gamma by enzyme-linked immunosorbent assay.
      Sputum eosinophils and EDN levels significantly increased at six and 24 hours
      postchallenge and were enhanced during the stress phase (p < 0.01). IL-5
      generation by sputum cells was also increased at 24 hours during stress and
      correlated with airway eosinophils (r(s) = 0.65, p < 0.05). Students' anxiety and
      depression scores were significantly higher during the examination period. Our
      findings suggest that stress associated with final examinations can act as a
      cofactor to increase eosinophilic airway inflammation to antigen challenge and
      thus may enhance asthma severity.

PMID- 11956046
TI  - Beta2-agonist tolerance and exercise-induced bronchospasm.
AB  - The effect of regular inhaled beta-agonist on the treatment of exercise-induced
      bronchoconstriction was studied. Eight subjects with exercise-induced
      bronchoconstriction took 1 week each of salbutamol 200 microg qid or placebo in a
      random-order, double-blind, crossover study. They then withheld this treatment
      for 8 hours before performing a dry-air, sub-maximal exercise challenge at a work
      rate previously shown to induce a 15% fall in forced expiratory volume in 1
      second (FEV1). Five minutes after exercise, they inhaled salbutamol 100, 100, and
      200 microg at 5-minute intervals. The mean pre-exercise FEV1 was similar on both
      study days. However, pretreatment for 1 week with salbutamol led to a
      significantly greater fall in FEV1 after exercise. The FEV1 remained lower than
      during the placebo arm despite the administration of salbutamol after exercise.
      This difference persisted 25 minutes after exercise. It is concluded that regular
      beta-agonist treatment leads to increased exercise-induced bronchoconstriction
      and a suboptimal bronchodilator response to beta-agonist. The data suggest that
      previous regular beta-agonist treatment may lead to a failure to respond to
      emergency bronchodilator treatment during an acute asthma attack and support
      current opinion that regular short-acting beta-agonist therapy should not be used
      to treat asthma.

PMID- 11956047
TI  - Expression of tachykinins in nonnociceptive vagal afferent neurons during
      respiratory viral infection in guinea pigs.
AB  - Immunohistochemistry was combined with retrograde labeling to characterize the
      effect of respiratory infection with Sendai virus on the number of Substance
      P/Neurokinin A-containing vagal afferent neurons whose cell bodies resided in the
      nodose ganglia and whose receptive fields were located in guinea pig trachea. Of
      the neurons labeled from the trachea of vehicle-inoculated guinea pigs, few
      stained positively for Substance P/Neurokinin A (approximately 3% of total
      labeled neurons). These neurons had small diameter cell bodies (mode = 16-20
      microm), a feature of nociceptive-like C-fibers. Viral infection (Day 4 after
      inoculation) was associated with a significantly greater number of labeled
      neurons containing Substance P/Neurokinin A (approximately 20% of total labeled
      neurons). The majority of these had a relatively large cell body diameter (mode =
      36- 40 microm), a feature of nonnociceptive afferent neurons. This induction
      appeared to be reversible as there were significantly fewer Substance
      P/Neurokinin A positive neurons in nodose ganglia from virus-inoculated guinea
      pigs at Day 28 after inoculation, a time point when virus-induced airway
      inflammation had all but resolved. These findings support the hypothesis that
      viral infection leads to a qualitative change in the vagal afferent innervation
      of guinea pig airways such that both small diameter nociceptive-like neurons and
      large diameter nonnociceptive neurons express tachykinins.

PMID- 11956048
TI  - Evidence for differential reflex regulation of cholinergic and noncholinergic
      parasympathetic nerves innervating the airways.
AB  - The hypothesis that cholinergic and nonadrenergic, noncholinergic parasympathetic
      nerves innervating the airways are subject to differential reflex regulation was
      addressed. Pronounced contractile and relaxant parasympathetic reflex responses
      could be evoked by intravenous histamine, laryngeal mucosal application of
      capsaicin, inhaled capsaicin, or electrical stimulation of the vagal afferent
      nerves projecting to the esophagus and abdominal viscera. These data suggest that
      activation of multiple vagal afferent nerve subtypes can initiate both
      cholinergic and noncholinergic parasympathetic reflexes in the airways.
      Conversely, hypoxia or activation of the diving response from the nose evoked
      only cholinergic contractile reflexes. All contractile and relaxant responses
      evoked by these stimuli were absent in vagotomized animals or in animals
      pretreated with the ganglionic blocker trimethaphan, confirming their reflex and
      parasympathetic nature. The data indicate that cholinergic and noncholinergic
      parasympathetic nerves regulating airway caliber in guinea pigs are comprised of
      two distinct parasympathetic pathways that are subject to differential reflex
      regulation. This previously unrecognized complexity of autonomic regulation of
      airway caliber has potentially important implications for the mechanisms of
      airways hyperresponsiveness.

PMID- 11956049
TI  - Sex-specific prediction equations for Vmax(FRC) in infancy: a multicenter
      collaborative study.
AB  - Measurements of maximal flow at functional residual capacity (Vmax(FRC)) from
      partial forced expiratory maneuvers remain the most popular method for assessing
      small airway function in infants and young children. However, the lack of
      appropriate reference data that are both applicable outside the centers that
      developed them and reflect the normal variability between healthy subjects has
      limited interpretation of Vmax(FRC) results in both clinical practice and
      research. To address this problem, we collated Vmax(FRC) data from 459 healthy
      infants (226 boys) tested on 654 occasions during the first 20 months of life
      from three collaborating centers. Multiple linear regression analysis indicated
      that sex, age, and length were important predictors of Vmax (FRC), which was, on
      average, 20% higher in girls than in boys during the first 9 months of life.
      (Vmax(FRC))0.5 (ml x second(-1)) = 4.22 + 0.00210 x length2 (cm) for boys (RSD =
      3.01; R2 = 0.48), and -1.23 + 0.242 x length for girls (RSD = 2.72; R2 = 0.49).
      Alternative models incorporating both age and length z scores are also described.
      Failure to use sex-specific prediction equations for Vmax(FRC) may preclude
      detection of clinically significant changes in girls and lead to false reports of
      diminished airway function in boys. Appropriate use of z scores, which indicate a
      "normal" range (z scores of 0 +/- 2) for Vmax(FRC), during infancy should also
      improve interpretation of both clinical and research studies.

PMID- 11956050
TI  - Urine bombesin-like peptide elevation precedes clinical evidence of
      bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) is a chronic lung disease of very low birth
      weight infants, associated with oxygen therapy, barotrauma, and/or infections.
      Improved medical care has led to a paradoxically increased incidence of BPD due
      to greater infant survival. Early prediction of BPD has proven challenging.
      Increased pulmonary neuroendocrine cells containing bombesin-like peptide
      immunoreactivity occur in infants with BPD. We hypothesized that elevated urine
      bombesin-like peptide levels precede BPD. One hundred thirty-two infants, 28
      weeks gestation or less, were studied. Urine bombesin-like peptide levels,
      determined by radioimmunoassay, were normalized for creatinine. BPD was defined
      as oxygen dependence at 36 weeks postmenstrual age. A first urine bombesin-like
      peptide level greater than 20,000 pg/mg creatinine (12,500 fmol/mg) between
      postnatal days 1-4 occurred among 54% of the infants who later developed BPD (p <
      or = 0.001), versus 10% among non-BPD infants (specificity 90%). Multivariable
      logistic regression analyses revealed that elevated urine bombesin-like peptide
      levels are associated with BPD (odds ratio 9.9, 95% confidence interval: 3.4, 29)
      (p < or = 0.001) after adjusting for all confounding factors. Thus, elevated
      bombesin-like peptide levels in these infants at 1-4 days after birth are
      associated with a 10-fold increased risk of developing BPD. Utilizing urine
      bombesin-like peptide for screening might permit early therapeutic interventions
      to reduce disease progression and could provide a target for new preventive
      therapies.

PMID- 11956051
TI  - Intravenous sildenafil lowers pulmonary vascular resistance in a model of
      neonatal pulmonary hypertension.
AB  - Persistent pulmonary hypertension secondary to meconium aspiration syndrome is an
      important cause of morbidity and mortality in the neonatal population. We
      investigated the use of the phosphodiesterase-5 inhibitor sildenafil, in its
      intravenous form, as a pulmonary vasodilator in a model of meconium aspiration
      syndrome. Pulmonary hypertension was induced in 18 piglets, by endotracheal
      instillation of human meconium, 6 piglets subsequently received an infusion of
      intravenous sildenafil for 2 hours, 6 received inhaled nitric oxide for 2 hours,
      and 6 control animals received no additional intervention. Meconium aspiration
      increased pulmonary vascular resistance by 70%, and increased oxygenation index
      by over 100%. Pulmonary vascular resistance remained elevated for the remainder
      of the study period in control animals. Inhaled nitric oxide reduced the
      pulmonary vascular resistance by 40% after 2 hours of treatment; intravenous
      sildenafil completely reversed the increase in pulmonary vascular resistance
      within 1 hour of commencing the infusion. Neither agent had an effect on systemic
      hemodynamics. Sildenafil also increased cardiac output by 30%, but while doing so
      did not adversely influence oxygenation. Intravenous sildenafil is a selective
      and highly effective pulmonary vasodilator, which is at least as effective as
      inhaled nitric oxide, in this model of neonatal persistent pulmonary
      hypertension.

PMID- 11956052
TI  - Severity of meningococcal disease in children and the angiotensin-converting
      enzyme insertion/deletion polymorphism.
AB  - Critical illness outcome may be causally related to inflammatory response
      severity. Given that tissue angiotensin-converting-enzyme (ACE) regulates such
      responses and that the deletion (D) [rather than insertion (I)] variant of the
      ACE gene is associated with higher tissue ACE levels, DD genotype might be
      associated with a poorer outcome in a uniform infectious disease state. Illness
      severity (Pediatric RIsk of Mortality score, the Glasgow Meningococcal
      Septicaemia Prognostic Score [GMSPS], and clinical course) was recorded for
      consecutive white patients with meningococcal disease (n = 110, 34 DD genotype,
      61 male, aged 49.4 +/- 5.4 months) referred to the Royal Liverpool Children's
      Hospital, UK. Compared with children with > or = I allele, DD genotype was
      associated with 14% higher predicted risk of mortality (p = 0.038), higher GMSPS
      (DD 9.4 +/- 0.5, ID/II 7.7+/- 0.4 [mean +/- SEM], p = 0.013), greater prevalence
      of inotropic support (76% versus 55%, p = 0.03) and ventilation (82% versus 63%,
      p = 0.04), and longer Pediatric Intensive Care Unit (PICU) stay (5.8 versus 3.9,
      p = 0.02). DD genotype frequency was 6% (1 case) for the 18 children who did not
      require PICU care, 33% for the 84 PICU survivors, and 45% for those who died (p =
      0.01). ACE DD is associated with increased illness severity in meningococcal
      disease.

PMID- 11956053
TI  - Pressure-volume curves in acute respiratory distress syndrome: clinical
      demonstration of the influence of expiratory flow limitation on the initial
      slope.
AB  - The presence of an initial segment with a low compliance on the static pressure
      volume (PV) curve in patients with acute respiratory distress syndrome (ARDS)
      indicates that some lung compartments do not initially receive insufflated gas.
      We tested the hypothesis that an uneven distribution of time constants, producing
      a "slow compartment," was in part responsible for the change in compliance
      between the initial and the intermediate segment of the PV curve. In 16 patients
      with ARDS submitted to mechanical ventilation in volume-controlled mode with a
      supportive respiratory rate of 15 breaths/minute, we constructed the static PV
      curve on the first day of respiratory support and determined the intrinsic
      positive end-expiratory pressure (PEEPi4) during a prolonged end-expiratory pause
      (4 seconds). We also measured the volume of a "slow compartment" during a
      prolonged expiration (> 6 seconds), and determined an external PEEP (PEEPe)
      suppressing PEEPi4. Among the 16 patients studied, 11 exhibited a low inflection
      point, associated with a "slow compartment" of 172 +/- 83 ml, responsible for a
      PEEPi4 of 3 +/- 2 cm H2O. Conversely, the five remaining patients had a linear PV
      curve, associated with a minimal "slow compartment" of 28 +/- 10 ml, responsible
      for a negligible PEEPi4. We observed that individual slopes of the initial
      segment of the PV curve were inversely and significantly correlated with the
      proportion of the "slow compartment" (r = -0.85). We concluded that the shape of
      the inspiratory PV curve in ARDS might be dependent on the presence of a "slow
      compartment," and demonstrated that a low external PEEP appeared sufficient to
      achieve a substantial mechanical improvement in clinical practice.

PMID- 11956054
TI  - Erythromycin inhibits rhinovirus infection in cultured human tracheal epithelial
      cells.
AB  - To examine the effects of erythromycin on rhinovirus (RV) infection in airway
      epithelium, primary cultures of human tracheal epithelial cells were infected
      with the RV major subgroup, RV14, and the minor subgroup, RV2. Infection was
      confirmed by increases in viral RNA of the infected cells and viral titers of the
      supernatants. RV14 upregulated the expression of the mRNA and protein of
      intercellular adhesion molecule-1 (ICAM-1), the major RV receptor, and it
      increased the cytokine production. Erythromycin reduced the supernatant RV14
      titers, RV14 RNA, the susceptibility to RV14 infection, and the production of
      ICAM-1 and cytokines. Erythromycin also reduced the supernatant RV2 titers, RV2
      RNA, the susceptibility to RV2 infection, and cytokine production, although the
      inhibitory effects of erythromycin on the expression of the low-density
      lipoprotein receptor, the minor RV receptor, were small. Erythromycin reduced the
      nuclear factor-kappaB activation by RV14 and decreased the number of acidic
      endosomes in the epithelial cells. These results suggest that erythromycin
      inhibits infection by the major RV subgroup by reducing ICAM-1 and infection by
      both RV subgroups by blocking the RV RNA entry into the endosomes. Erythromycin
      may also modulate airway inflammation by reducing the production of
      proinflammatory cytokines and ICAM-1 induced by RV infection.

PMID- 11956055
TI  - Increased frequency of the uncommon tumor necrosis factor -857T allele in British
      and Dutch patients with sarcoidosis.
AB  - Interindividual variation in the expression of tumor necrosis factor (TNF)-alpha
      suggests the existence of functionally distinct TNF alleles, which might play a
      role in sarcoidosis. We investigated five potentially functional biallelic TNF
      promoter polymorphisms at nucleotide positions -1,031(T/C), -863(C/A), -857(C/T),
      -307(G/A), and -237(G/A) in two clinically well-defined groups of white patients
      (British [UK] and Dutch [NL]) with sarcoidosis, each with their own control
      subjects. Polymorphisms were determined using SSP-PCR. A total of 772 individuals
      were studied (96 UK patients, 354 UK control subjects, 100 NL patients, 222 NL
      controls). A significant increase in the rarer TNF -857T allele was found in both
      sarcoidosis populations. In total 25.5% of the sarcoid patients carried the TNF 
      857T allele versus 14.1% of the control subjects (p = 0.003, p(c) = 0.02). In the
      sarcoidosis group the allele frequency of this polymorphism was 13.5% versus 7.3%
      in the control subjects (p = 0.0003, p(c) = 0.002). Subgroup analysis showed a
      significant increase in the rarer TNF -307A (TNF-2) allele in patients with
      Lofgren's syndrome (p = 0.006, p(c) = 0.03). Our finding does not necessarily
      imply that the two polymorphisms relate to different functions; it may be that
      one or both are in linkage disequilibrium with the causal site. This requires
      further studies of functionality and linkage disequilibrium.

PMID- 11956056
TI  - Elevated levels of thymus- and activation-regulated chemokine in bronchoalveolar
      lavage fluid from patients with eosinophilic pneumonia.
AB  - Thymus- and activation-regulated chemokine (TARC/CCL17) is a lymphocyte-directed
      CC chemokine, which plays a role in the recruitment of CC chemokine receptor-4
      positive T helper 2 (Th2) cells. In this study, we measured concentrations of
      TARC and Th2 cell-derived cytokines in bronchoalveolar lavage (BAL) fluid, as
      well as TARC concentrations in serum from patients with eosinophilic pneumonia
      and other interstitial lung diseases. TARC was significantly elevated in BAL
      fluids from patients with eosinophilic pneumonia (median, 240 pg/ml), whereas
      TARC was undetectable (< 7 pg/ml) in most cases of hypersensitivity pneumonitis,
      sarcoidosis, and idiopathic pulmonary fibrosis, as well as in healthy control
      subjects. Also, when present, quantities were less than 20 pg/ml. Elevated
      concentrations of interleukin (IL)-4, IL-5, and IL-13 were also detected in BAL
      fluid from patients with eosinophilic pneumonia. Interestingly, TARC
      concentrations in BAL fluids were closely correlated with the concentrations of
      IL-5 and IL-13. A serial examination showed that elevated TARC in BAL fluid
      rapidly fell to below detectable limits preceding decreases in IL-5 concentration
      and eosinophil percentage. Our results, in concordance with previous studies,
      demonstrate the potential activity of TARC for recruiting Th2 cells to the lungs
      and suggest a significant role for TARC in the pathogenesis of eosinophilic
      pneumonia.

PMID- 11956057
TI  - Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1) gene in
      the asthmatic airway.
AB  - Mucus overproduction is a clinical feature of asthma. Ca2+-activated Cl- channel
      1 (CaCC1) has been identified as a protein that is expressed in intestinal
      epithelia and that plays an important role in fluid and electrolyte transport.
      Recently, its mouse counterpart, gob-5, was identified as a key molecule in the
      induction of murine asthma through mucus overproduction. To elucidate the
      relationship of CaCC1 to human asthma, we examined CaCC1 expression using real
      time quantitative polymerase chain reaction analysis in bronchial tissues from
      patients with asthma and normal control subjects. The expression of CaCC1 was
      significantly upregulated in patients with bronchial asthma compared with control
      subjects. In situ hybridization and immunohistochemical analysis demonstrated
      that CaCC1 is located in the bronchial epithelium, especially in mucus-producing
      goblet cells. In vitro transfection of a CaCC1 expression vector into the human
      mucoepidermoid cell line, NCI-H292, increased mucus production and induced the
      MUC5AC gene. These results suggest that CaCC1 plays a direct role in mucus
      production and differentiation in goblet cells and may contribute to the
      pathogenesis of asthma through its mucus-inducing activity.

PMID- 11956059
TI  - Fatal asbestosis 50 years after brief high intensity exposure in a vermiculite
      expansion plant.
AB  - The authors report the case of a 65-year-old accountant whose only asbestos
      exposure was during a summer job 50 years earlier in a California vermiculite
      expansion plant. Vermiculite is a silicate material that is useful in building
      and agriculture as a filler and insulating agent. He developed extensive
      fibrocalcific pleural plaques and end-stage pulmonary fibrosis, with rapidly
      progressive respiratory failure. Careful occupational and environmental history
      revealed no other source of asbestos exposure, and the initial clinical diagnosis
      was idiopathic pulmonary fibrosis; open lung biopsy shortly before his death
      confirmed asbestosis. Electron microscopic lung fiber burden analysis revealed
      over 8,000,000 asbestos fibers per gram dry lung, 68% of which were tremolite
      asbestos. Additional asbestiform fibers of composition not matching any of the
      standard asbestos varieties were also present at over 5,000,000 fibers per gram
      dry lung. Comparison analysis of a sample of Libby, Montana, vermiculite showed a
      similar mix of asbestiform fibers including tremolite asbestos. This case
      analysis raises several concerns: risks of vermiculite induced disease among
      former workers of the more than 200 expansion plants throughout the United
      States; health effects of brief but very high-intensity exposures to asbestos;
      and possible health effects in end-users of consumer products containing
      vermiculite.

PMID- 11956058
TI  - Regulation of airway hyperresponsiveness by calcitonin gene-related peptide in
      allergen sensitized and challenged mice.
AB  - Sensory neuropeptides are localized to airway nerves and endocrine cells in both
      human and animal species and may participate in the development of airway
      inflammation and hyperresponsiveness (AHR). We used a mouse model to identify the
      changes that occur in calcitonin gene-related peptide (CGRP) expression in the
      airways during development of allergic inflammation and to investigate the
      potential role of this neuropeptide in modulating AHR. In sensitized mice,
      allergen challenge induced eosinophilic airway inflammation and AHR and resulted
      in considerable depletion of CGRP in neuroepithelial bodies and submucosal nerve
      plexuses without altering the overall density of airway nerve fibers. This
      depletion was subsequent to the development of airway inflammation and was
      prevented by anti-very late antigen-4 and anti-interleukin-5 treatments, which
      blocked airway eosinophilia and abolished AHR. Administration of CGRP to
      sensitized and challenged mice resulted in the normalization of airway
      responsiveness to inhaled methacholine, an effect that was neutralized by the
      receptor antagonist CGRP(8-37). These data demonstrate that replacement of CGRP
      following its depletion in allergic mice can reverse the changes in airway
      responsiveness and suggest that CGRP may have potential for the treatment of
      allergic AHR.

PMID- 11956060
TI  - One-night mandibular advancement titration for obstructive sleep apnea syndrome:
      a pilot study.
AB  - The effect of a dental appliance (DA) is usually evaluated in a single mandibular
      position reached after several weeks and corresponding to either improvement of
      symptoms or intolerance to any further advancement. The purpose of this study was
      to test the feasibility of one-night evaluation of the efficacy of a DA. The
      study population consisted of seven patients (six men) with obstructive sleep
      apnea syndrome (66.9 +/- 32.4 apneas and/or hypopneas per hour). Patients
      underwent two consecutive polysomnographies; first with a temporary DA (two
      arches connected by a hydraulic system) progressively adjusted during the night
      to correct sleep disordered breathing and second with a permanent DA (two arches
      connected by Herbst attachments) set to the effective degree of advancement
      during the titration night. All patients completed the protocol. The mean
      mandibular advancement reached during the titration night was 12.6 +/- 2.7 mm.
      Arousal was never observed during or for 60 seconds following advancement. The
      apnea-hypopnea index (AHI) was significantly reduced from 66.9 +/- 32.4 to 26.1
      +/- 20.7 per hour during the titration night from the diagnostic night (p <
      0.01). During the second night, the AHI was 19.6 +/- 20.2 per hour and was less
      than 20 per hour in 71.4% of patients and less than 10 per hour in 42.9% of
      patients. The efficacy of a DA can be evaluated during a single night of
      polysomnography.

PMID- 11956061
TI  - Selective cyclooxygenase-1 and -2 inhibitors each increase allergic inflammation
      and airway hyperresponsiveness in mice.
AB  - Nonselective cyclooxygenase (COX) inhibition during allergic sensitization with
      ovalbumin in a murine model leads to an increase in the Type 2 cytokines
      interleukin-5 (IL-5) and IL-13; however, the effect of selective COX-1 and COX-2
      inhibitors on these cytokines is unknown. We found that COX-1 protein was
      constitutively expressed in lung tissue. Expression of COX-1 protein did not
      increase with ovalbumin sensitization, but expression of COX-2 protein did.
      Ovalbumin-sensitized mice treated with either selective COX-1 inhibitor SC58560
      (OVA-COX-1 inhibitor) or selective COX-2 inhibitor SC58236 (OVA-COX-2 inhibitor)
      had significantly greater airway hyperresponsiveness (p < 0.05) and higher levels
      of IL-13 (p < 0.05) in lung supernatants than did untreated mice that were
      ovalbumin sensitized (OVA). Lung mRNA levels for the chemokine receptors CCR1
      through CCR5 (expressed on eosinophils, basophils, lymphocytes, and dendritic
      cells) were increased in the OVA-COX-2 inhibitor and OVA-indomethacin groups. We
      conclude that in the BALB/c mouse, COX inhibition with either a COX-1 or COX-2
      inhibitor during allergen sensitization augments production of IL-13 and
      increases airway hyperresponsiveness.

PMID- 11956062
TI  - Selective induction of eotaxin release by interleukin-13 or interleukin-4 in
      human airway smooth muscle cells is synergistic with interleukin-1beta and is
      mediated by the interleukin-4 receptor alpha-chain.
AB  - The biologic activities of interleukin (IL)-13 and IL-4 often overlap, and
      evidence supports their importance in atopic disease and airways
      hyperresponsiveness. Here, their capacity to release eosinophil-activating
      cytokines was examined in cultured human airway smooth muscle. IL-13 and IL-4
      induced selective release of eotaxin with no effect on granulocyte-macrophage
      colony-stimulating factor, regulated upon activation, normal T-cell expressed and
      secreted (RANTES), or IL-8. A profound synergistic increase in eotaxin release
      occurred when IL-13 or IL-4 was combined with IL-1beta that was abrogated by a
      neutralizing antibody to the IL-4 receptor alpha (IL-4Ralpha)-chain but not to
      the IL-2 receptor gamma (IL-2Rgamma)-chain. Expression of cell surface IL-4
      receptors and IL-4Ralpha in lysates was constitutive and unchanged by treatment
      with IL-13 or IL-4 alone or in combination with IL-1beta. Activation of IL
      4Ralpha by IL-13 or IL-4 induced signal transducer and activation of
      transcription-6 (STAT6), p42/ p44 ERK, p38, and to a lesser extent, SAPK/JNK
      mitogen-activated protein kinase phosphorylation. STAT6 and MAP kinase activation
      by IL-13 or IL-4 was not further potentiated after combined stimulation with IL
      1beta. However, eotaxin release induced by IL-13 or IL-4 alone, and in
      combination with IL-1beta, was prevented by the MEK inhibitor U 0126 and by the
      p38 inhibitor SB 202190. Collectively, the data suggest that selective eotaxin
      release induced either by IL-13 and IL-4 or when combined with IL-1beta is
      mediated by a constitutive cell surface IL-4Ralpha and the activation of multiple
      intracellular pathways.

PMID- 11956063
TI  - Clinical findings and lung pathology in children with cystic fibrosis.
AB  - Cystic fibrosis pulmonary disease is assessed by pulmonary function tests,
      arterial blood gases, and chest X-rays, but the correlation with lung pathology
      is unknown. We reviewed the clinical findings and lung pathology of 21 cystic
      fibrosis patients who had lung transplant. Pulmonary function tests, Brasfield
      scores, arterial blood gases, and age were correlated with lung pathology. All
      patients had severe Brasfield scores (9.0 +/- 3.2), airways obstruction (FEV1
      25.6 +/- 5.6% predicted, FEF(25-75%) 11.0 +/- 4.5% predicted), and hyperinflation
      (residual volume [RV] 341.8 +/- 75.8% predicted). All patients were hypoxemic
      (PO2 64.2 +/- 8.2 mm Hg), and 5 of 21 (24%) were hypercapneic (PCO2 > 50 mm Hg).
      Pulmonary function tests and Brasfield scores were within a narrow range, and did
      not allow correlation with lung pathology. Small airway density (airways < 2
      mm/cm2) decreased with increasing age. There were no differences in small airways
      inflammation and fibrous narrowing between the hypercapneic and nonhypercapneic
      patients, but the percent of smallest airways (airways < 0.35 mm) was
      significantly lower in the hypercapneic group. We conclude that there is
      significant correlation between airway pathology and increased age and CO2
      retention. We speculate that decreased small airway density in older patients and
      the decreased proportion of smallest airways in hypercapneic patients is caused
      by increased dilatation of small airways.

PMID- 11956064
TI  - Prolonged inflammatory response to acute Pseudomonas challenge in interleukin-10
      knockout mice.
AB  - Cystic fibrosis (CF) lung disease is characterized by a neutrophilic infiltrate
      that is excessive relative to the burden of infection. Decreased interleukin-10
      in CF airways may impair proper termination of inflammation, leading to
      persistence of neutrophils after acute infections have been cleared. This could
      explain reports of lung inflammation in the absence of bacteria in infants with
      CF. We evaluated the kinetics of inflammation after transient Pseudomonas
      aeruginosa challenge in IL-10 knockout (KO) and wild-type (WT) mice. Both types
      of mice cleared the infection by Day 6 (p > or = 0.29). However, IL-10 KO mice
      had more neutrophils in bronchoalveolar lavage fluid than did WT mice on Days 4
      (p < 0.0001), 6 (p < 0.0001), and 8 (p = 0.042). IL-10 KO mice had high
      concentrations of proinflammatory cytokines in BAL on Days 2 and 4, with some
      cytokines detectable on Days 6 and 8, whereas cytokines in BAL from WT mice were
      greatest on Day 2 and undetectable by Day 4. Moreover, IL-10 KO mice failed to
      regenerate IkappaBalpha once degraded and subsequently had prolonged activation
      of NF-kappaB. These data suggest that IL-10 deficiency contributes to prolonged
      inflammatory responses early in CF, when infection may be transient.

PMID- 11956065
TI  - Selecting the right level of positive end-expiratory pressure in patients with
      acute respiratory distress syndrome.

PMID- 11956066
TI  - Magnetic resonance imaging of the upper airway in children with Down syndrome.

PMID- 11956067
TI  - Passive smoke and exhaled nitric oxide.

PMID- 11956068
TI  - Budesonide dose-response in mild persistent asthma.

PMID- 11956070
TI  - c-myc-induced apoptosis in polycystic kidney disease is independent of FasL/Fas
      interaction.
AB  - Apoptosis is a critical early cellular event in the development of polycystic
      kidney disease (PKD) in humans and mice. In the SBM transgenic model of PKD, both
      apoptosis and proliferation are c-myc driven and are independent of p53 and Bcl-2
      pathways. On the basis of recent evidence implicating the FasL/Fas pathway in c
      myc-induced apoptosis, we investigated the potential interaction of these
      pathways in vivo. We first evaluated the expression of FasL in renal tissues of
      SBM mice. This analysis showed that the level of FasL expression was elevated 3-4
      fold in the SBM kidneys, indicating a potential autocrine suicidal mechanism. We
      next crossed the SBM mice with gld mice mutated in FasL. The progenies had
      comparable renal epithelial apoptotic and proliferation rates and a cystic
      phenotype in all SBM genotypes irrespective of the FasL genotype. Our study
      proves that c-myc-induced apoptosis can be independent of the FasL/Fas pathway in
      vivo and implicates the existence of a novel c-myc-driven apoptotic pathway.

PMID- 11956069
TI  - Identification of the p33(ING1)-regulated genes that include cyclin B1 and proto
      oncogene DEK by using cDNA microarray in a mouse mammary epithelial cell line
      NMuMG.
AB  - The candidate tumor suppressor p33(ING1) plays an important role in
      inducinggrowth arrest at G(0)-G(1) phase of the cell cycle and/or promoting
      apoptosis in cancerous cells. p33(ING1) is reported to act as a transcriptional
      cofactor by associating with tumor suppressor p53, HAT, or histone
      deacetyltransferase, suggesting that p33(ING1) is involved in chromatin-mediated
      transcriptional regulation. However, the molecular mechanism of p33(ING1)
      mediated transcriptional regulation is poorly understood. Here we analyzed
      expression profiles in mouse mammary epithelial cells (NMuMG) by using a cDNA
      microarray consisting of 2304 mouse cDNAs after inducing transformation with
      antisense inhibitor of growth 1 (ING1) in retrovirus vector. The subsequent
      confirmation of the altered expression levels of the selected genes by
      semiquantitative reverse transcription-PCR demonstrated that overexpression of
      the antisense ING1 stimulated expression of 14 genes, which included cyclin B1,
      12-O-tetradecanoylphorbol-13-acetate-inducible sequence 11, proto-oncogene DEK,
      and osteopontin, whereas we have detected transcriptional repression of 5 genes,
      including TPT1. In addition, adenovirus-mediated overexpression of ING1 in NMuMG
      cells resulted in down-regulation of cyclin B1, 12-O-tetradecanoylphorbol-13
      acetate-inducible sequence 11, DEK, and osteopontin, whereas the levels of TPT1
      expression were increased. The further analysis using p53(-/-) SAOS2 cells showed
      that the p33(ING1)-induced cyclin B1 down-regulation was p53 dependent. Thus, our
      cDNA microarray analysis suggested that p33(ING1) targets the multiple genes,
      including proto-oncogene DEK and cyclin B1, at least some of which are regulated
      in a p53-dependent manner, in the cells undergoing cell growth or apoptosis.

PMID- 11956071
TI  - Forced expression of NESH suppresses motility and metastatic dissemination of
      malignant cells.
AB  - To characterize the function of a novel Src homology 3 (SH3) adapter protein
      termed NESH, we have established transfectants stably expressing NESH. We
      observed that every clone of NESH transfectants caused a marked reduction in
      motility, although the clones exhibited no significant differences in intrinsic
      cell growth compared with the control cells in vitro. The NESH transfectants also
      exhibited significant reduction in tumor metastatic potential in vivo. We found
      that NESH expression is frequently lost in invasive cancer cell lines despite its
      ubiquitous expression in normal tissues. The SH3 domain of NESH seems to interact
      with p21-activated kinase (PAK), which is involved in regulation of cell
      motility. Furthermore, a significant decrease in PAK phosphorylation at (402)Thr
      was found in NESH transfectants. Taken together, these results suggest that NESH
      inhibits ectopic metastasis of tumor cells as well as cell migration through
      interaction with intracellular molecules such as PAK that are essential for cell
      motility.

PMID- 11956073
TI  - Cholesterol-rich lipid rafts mediate akt-regulated survival in prostate cancer
      cells.
AB  - Although cholesterol accumulation in tumors was first reported in the early20th
      century, the mechanistic implications of this observation are still obscure. Here
      we report that caveolin-negative human prostate cancer (LNCaP) cells contain
      cholesterol-rich lipid rafts that mediate epidermal growth factor (EGF)-induced
      and constitutive signaling through the Akt1 serine-threonine kinase. EGF receptor
      and Akt1 phosphorylation were inhibited and autonomous cell survival was reduced
      when the rafts were disrupted. Reconstitution of the rafts with cholesterol
      restored EGF receptor-->Akt1 axis signaling and cytoprotection from a
      phosphoinositide 3-kinase-dependent apoptotic signal. These results suggest that
      cholesterol present in membrane microdomains is a prominent mediator of survival
      in prostate cancer cells.

PMID- 11956072
TI  - Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer.
AB  - Identification of genes that are dysregulated in association with prostate
      carcinogenesis can provide disease markers and clues relevant to disease
      etiology. Of particular interest as candidate markers of disease are those genes
      that are frequently overexpressed. In this study, we describe a gene, alpha
      methylacyl-CoA racemase (AMACR), whose expression is consistently up-regulated in
      prostate cancer. Analysis of mRNA levels of AMACR revealed an average up
      regulation of approximately 9 fold in clinical prostate cancer specimens compared
      with normal. Western blot and immunohistochemical analysis confirms the up
      regulation at the protein level and localizes the enzyme predominantly to the
      peroxisomal compartment of prostate cancer cells. A detailed immunohistochemical
      analysis of samples from 168 primary prostate cancer cases using both standard
      slides and tissue microarrays demonstrates that both prostate carcinomas and the
      presumed precursor lesion (high-grade prostatic intraepithelial neoplasia)
      consistently scored significantly higher than matched normal prostate epithelium;
      88% of the carcinomas had a staining score higher than the highest score observed
      for any sample of normal prostate epithelium. Both untreated metastases (n = 32
      patients) and hormone refractory prostate cancers (n = 14 patients) were
      generally strongly positive for AMACR. To extend the utility of this marker for
      prostate cancer diagnosis, we combined staining for cytoplasmic AMACR with
      staining for the nuclear protein, p63, a basal cell marker in the prostate that
      is absent in prostate cancer. In a simple assay that can be useful for the
      diagnosis of prostate cancer on both biopsy and surgical specimens, combined
      staining for p63 and AMACR resulted in a staining pattern that greatly
      facilitated the identification of malignant prostate cells. The enzyme encoded by
      the AMACR gene plays a critical role in peroxisomal beta oxidation of branched
      chain fatty acid molecules. These observations could have important
      epidemiological and preventive implications for prostate cancer, as the main
      sources of branched chain fatty acids are dairy products and beef, the
      consumption of which has been associated with an increased risk for prostate
      cancer in multiple studies. On the basis of its consistency and magnitude of
      cancer cell-specific expression, we propose AMACR as an important new marker of
      prostate cancer and that its use in combination with p63 staining will form the
      basis for an improved staining method for the identification of prostate
      carcinomas. Furthermore, the absence of AMACR staining in the vast majority of
      normal tissues coupled with its enzymatic activity makes AMACR the ideal
      candidate for development of molecular probes for the noninvasive identification
      of prostate cancer by imaging modalities.

PMID- 11956074
TI  - Acceleration of G(1) cooperates with core binding factor beta-smooth muscle
      myosin heavy chain to induce acute leukemia in mice.
AB  - The genes encoding the AML1 (RUNX1) or CBFbeta subunits of core binding factor
      (CBF) are commonly altered by translocation or mutation in human leukemias.
      Because CBF oncoproteins slow G(1), we sought to determine whether mutations that
      accelerate G(1) potentiate their ability to induce transformation. Wild-type or
      p16(INK4a)p19(ARF) (-/-) marrow cells transduced with CBFbeta-smooth muscle
      myosin heavy chain (SMMHC) were transplanted into wild-type, syngeneic
      recipients. CBFbeta-SMMHC significantly increased the development of acute
      leukemias from marrow lacking the overlapping p16p19 genes, based on analysis of
      Kaplan-Meier event-time distributions. Wild-type marrow was also transduced with
      vectors expressing either E7 alone or both E7 and CBFbeta-SMMHC. Combining
      oncogenes again increased leukemia formation. Exposing mice transplanted with
      CBFbeta-SMMHC-transduced cells to a mutagen, ethylnitrosourea, markedly
      accelerated leukemogenesis compared to expressing CBFbeta-SMMHC with loss of
      p16p19, indicating the need for multiple "hits" for transformation. The
      INV/p16p19 and INV/E7 leukemias were lymphoid and were clonal and
      retransplantable. Overall, these findings indicate that CBF mutations cooperate
      with genetic alterations that accelerate G(1) to induce acute leukemia.

PMID- 11956075
TI  - Significant increase of colonic mutated crypts in ulcerative colitis
      correlatively with duration of illness.
AB  - Mild periodic acid-Schiff (mPAS) staining can discriminate non-O-acetylated(mPAS
      positive) from O-acetylated (mPAS negative) epithelial sialoglycoproteins in
      human colonic mucosa, giving three haplotypes of expression of a single
      polymorphic autosomal gene (oat). Increase in mPAS-positive crypts in
      heterozygotes is an indication of mutations, and wholly mPAS-positive (stem cell
      mutated) crypts and clusters of two or more mPAS-positive crypts in heterozygotes
      of ulcerative colitis (P < 0.0001) were found to be increased significantly,
      compared with controls. The observed correlation with ulcerative colitis duration
      (r = 0.892 and 0.853, respectively) supports a chronic inflammation-carcinoma
      sequence.

PMID- 11956077
TI  - Antihuman epidermal growth factor receptor 2 (HER2) monoclonal antibody
      trastuzumab enhances cytolytic activity of class I-restricted HER2-specific T
      lymphocytes against HER2-overexpressing tumor cells.
AB  - The monoclonal antibody trastuzumab (Herceptin) directed against the human
      epidermal growth factor receptor 2 (HER2) results in tumor regressions when
      administered to patients with HER2-overexpressing breast cancer. One of the
      underlying mechanisms of this antibody-induced tumor regression is based on the
      internalization and degradation of HER2 by tumor cells on interaction with
      trastuzumab, subsequently inhibiting signal transduction pathways. As antibody
      induced degradation of HER2 is likely to be accompanied with increased numbers of
      HER2 peptides presented with MHC, we asked whether trastuzumab-treated tumor
      cells were more susceptible to CTL-mediated lysis. Here we show that the
      cytolytic activity of human, HER2-specific CD8(+) CTLs is augmented by anti-HER2
      antibody trastuzumab. HER2-reactive CTL clones lyse class I-matched, HER2
      overexpressing tumor cells more efficiently after treatment with trastuzumab. The
      potentially synergistic activity of HER2-specific antibody and CTL encourages the
      development of an HER2-targeted immunotherapy using a combination of inhibitory
      antibodies and CTLs for patients with HER2-overexpressing tumors.

PMID- 11956076
TI  - Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7)
      induces apoptosis of lung cancer cells via up-regulation of the double-stranded
      RNA-dependent protein kinase (PKR).
AB  - Adenoviral-mediated overexpression of the melanoma differentiation-associated
      gene 7 (Ad-mda7) induces apoptosis in a wide range of cancer cells, although
      themechanism is not well understood. We report that Ad-mda7 induces andactivates
      the double-stranded RNA-dependent protein kinase (PKR), which leads to
      phosphorylation of the alpha subunit of eukaryotic translation initiation factor
      2 (eIF-2alpha) and the induction of apoptosis in lung cancer cells. Treatment
      with 2-aminopurine (2-AP), a serine/threonine kinase inhibitor, inhibits PKR
      activation, eIF2alpha phosphorylation, and apoptosis induction by Ad-mda7.
      Additionally, PKR null but not wild-type fibroblasts are resistant to Ad-mda7
      induced apoptosis. These results suggest that the activation of PKR and its
      downstream targets may be a critical pathway for Ad-mda7-mediated apoptosis.

PMID- 11956078
TI  - Glutathione S-transferase P1 and NADPH quinone oxidoreductase polymorphisms are
      associated with aberrant promoter methylation of P16(INK4a) and O(6)
      methylguanine-DNA methyltransferase in sputum.
AB  - Inactivation of the p16(INK4a) tumor suppressor gene and O(6)-methylguanine-DNA
      methyltransferase (MGMT) DNA repair gene by aberrant promoter methylation appears
      to be an important step in respiratory carcinogenesis after exposure to tobacco
      smoke and radon progeny. The determinants of aberrant promoter methylation are
      not well characterized. Polymorphic variants of genes of which the products are
      involved in pathways that modulate and repair DNA damage after carcinogen
      exposure may affect the occurrence of de novo promoter methylation. On the basis
      of their associations with risk of lung cancer, we hypothesized that functional
      polymorphic variants of the NADPH quinone oxidoreductase, glutathione S
      transferases P1 and M1, myeloperoxidase, and XRCC1 genes are associated with p16
      and/or MGMT promoter methylation in sputum from cancer-free subjects at high risk
      for developing lung cancer. This hypothesis was tested by conducting a cross
      sectional study of 70 former uranium miners from the Uranium Epidemiological
      Study cohort who were at high risk for lung cancer. The polymorphic variant
      genotypes were characterized through PCR-RFLP on DNA isolated from peripheral
      lymphocytes, and the methylation status of the p16 and MGMT promoters was
      determined by methylation-specific PCR on DNA isolated from sputum. Subjects who
      had at least one GSTP1 polymorphic allele (A-to-G at bp 104) had an increased
      risk for MGMT methylation [odds ratio (OR), 4.8; 95% confidence interval (CI),
      1.2-18.6] or for either p16 or MGMT methylation (OR, 4.4; 95% CI, 1.3-14.2). Lack
      of a wild-type NADPH quinone oxidoreductase allele (C at bp 609) was also
      associated with methylation of either p16 or MGMT (OR, 3.1; 95% CI, 1.0-9.2).
      These results provide the first link between germ-line functional deficits in
      pathways that protect the cell from tobacco- and radon-induced DNA damage, and
      the development of aberrant promoter methylation of the p16 and MGMT genes in the
      respiratory epithelium of individuals at high risk for lung cancer.

PMID- 11956079
TI  - Associations between hOGG1 sequence variants and prostate cancer susceptibility.
AB  - 8-Hydroxyguanine is a mutagenic base lesion produced by reactive oxygen species.
      The hOGG1 gene encodes a DNA glycosylase/AP lyase that can suppress the mutagenic
      effects of 8-hydroxyguanine by catalyzing its removal from oxidized DNA. A
      population-based (245 cases and 222 controls) and family-based (159 hereditary
      prostate cancer families) association study was performed to test the hypothesis
      that sequence variants of hOGG1 increase susceptibility to prostate cancer. We
      found that the genotype frequency of two sequence variants (11657A/G and
      Ser326Cys) was significantly different between cases and controls. The
      association with 11657A/G is confirmed and strengthened by our family-based
      association study. These results suggest that sequence variants in this gene are
      associated with prostate cancer risk, presumably through defective DNA repair
      function of hOGG1.

PMID- 11956080
TI  - Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell
      carcinoma.
AB  - The WWOX (WW domain containing oxidoreductase) gene was recently identified as a
      candidate tumor suppressor gene at 16q23.3-24.1, a chromosome region that spans
      the common fragile site FRA16D. To evaluate the potential role of the WWOX gene
      in esophageal squamous cell carcinomas, we examined 36 tumors for genetic
      alterations of the WWOX gene. Loss of heterozygosity (LOH) at the WWOX locus was
      observed in 14 (39%) tumors. A tumor-specific missense mutation was found in one
      tumor, and LOH analysis had shown that the other allele was missing. Furthermore,
      we detected aberrant WWOX gene transcripts with absence of exons 6-8 in two
      tumors, and complete absence of transcript in one tumor. These results indicate
      that alteration and inactivation of the WWOX gene may play a role in esophageal
      squamous cell carcinogenesis.

PMID- 11956081
TI  - Gastrointestinal hamartomatous polyposis in Lkb1 heterozygous knockout mice.
AB  - Peutz-Jeghers syndrome (PJS) is a hereditary disorder characterized by
      gastrointestinal hamartomatous polyposis associated with mucocutaneous
      pigmentation. Germ-line mutations of the gene encoding LKB1 (STK11), a
      serine/threonine kinase, are identified in most PJS patients. To investigate the
      role of LKB1 in the PJS phenotypes, we introduced a germ-line mutation in the
      mouse Lkb1 gene by homologous recombination in mouse embryonic stem cells. In
      most Lkb1 (+/-) mice >20 weeks of age, hamartomatous polyps developed in the
      glandular stomach, often in the pyloric region. Small intestinal hamartomas also
      developed in approximately one-third of the Lkb1 (+/-) mice >50 weeks of age. A
      genomic PCR and sequence analysis showed that all hamartomas retained both the
      wild-type and targeted Lkb1 alleles, indicating that allelic loss of the wild
      type Lkb1 was not the cause of polyp formation. Moreover, the LKB1 protein level
      was not reduced in hamartomatous polyps compared with that in the Lkb1 (+/-)
      normal gastric mucosa. In addition, the remaining allele showed neither missense
      mutations in the coding sequence nor produced truncated LKB1 in the hamartoma.
      Taken together, these data suggest that the wild-type Lkb1 is expressed in the
      hamartoma at the haploid amount. Accordingly, the gastrointestinal hamartomas
      appear to develop because of the Lkb1 haploinsufficiency. Although additional
      genetic events may be critical in hamartoma and adenocarcinoma development, these
      data strongly suggest that the initiation of polyposis is not the result of loss
      of heterozygosity in Lkb1.

PMID- 11956082
TI  - Rate-limiting effects of Cyclin D1 in transformation by ErbB2 predicts synergy
      between herceptin and flavopiridol.
AB  - Cyclin D1 is downstream of erbB2 and is required for erbB2 transformation. Here
      we report thatcyclin D1 functions are essential, rate limiting for erbB2
      transformation, and reciprocally increase erbB2 levels. This interaction depends
      on three cyclin D1 activities: cyclin-dependent kinase 4-dependent kinase
      activity, titration of p27, and an intrinsic transcriptional activity of cyclin
      D1. Drugs active against erbB2 and cyclin D1 (Herceptin and flavopiridol) were
      synergistically cytotoxic against erbB2-positive breast cancer cell lines.
      Addition of flavopiridol to Herceptin synergistically lowered erbB2 levels in
      these cells. Our data suggest the potential use of combinations of cyclin
      dependent kinase inhibitors and Herceptin in breast cancer.

PMID- 11956083
TI  - Inhibition of protein synthesis in apoptosis: differential requirements by the
      tumor necrosis factor alpha family and a DNA-damaging agent for caspases and the
      double-stranded RNA-dependent protein kinase.
AB  - Exposure of mammalian cells to agents that induce apoptosis results in a rapid
      and substantial inhibition of protein synthesis. In MCF-7 breast cancer cells,
      tumor necrosis factor alpha (TNFalpha) and TNF-related apoptosis-inducing ligand
      inhibit overall translation by a mechanism that requires caspase (but not
      necessarily caspase-3) activity. This inhibition is associated with the increased
      phosphorylation of eukaryotic initiation factor (eIF2) alpha, increased
      association of eIF4E with the inhibitory eIF4E-binding protein (4E-BP1), and
      specific cleavages of eIF4B and eIF2alpha. All of these changes require caspase
      activity. The cleavage of eIF4GI, which specifically needs caspase-3 activity, is
      dispensable for the inhibition of translation in MCF-7 cells. Similar experiments
      with embryonic fibroblasts from control mice and animals defective for expression
      of the double-stranded RNA-regulated protein kinase (PKR) reveal requirements for
      both caspase activity and PKR for inhibition of protein synthesis in response to
      TNFalpha. In contrast, treatment of cells with the DNA-damaging agent etoposide
      inhibits protein synthesis equally well in the presence of a pan-specific caspase
      inhibitor and in the presence or absence of PKR. Surprisingly, the ability of
      etoposide to cause increased association of eIF4E with 4E-BP1 does require PKR
      activity. However, our data suggest that neither increased phosphorylation of
      eIF2alpha nor increased [eIF4E.4E-BP1] complex formation is essential for the
      inhibition of overall translation by the DNA-damaging agent.

PMID- 11956084
TI  - Absence of the CD44 gene prevents sarcoma metastasis.
AB  - To test the role of the CD44 gene in tumorigenesis, mice with the min mutation of
      the APC gene or with the tm1 mutation of the p53 gene were crossed with CD44
      knockout mice. The absence of CD44 gene products did not affect tumor incidence
      or survival; however, mice with disruption of the CD44 gene showed virtually
      aborted metastasis formation of osteosarcomas. This is in agreement with the role
      attributed to CD44 variants in the spread of cancer. Therefore, CD44 gene
      products are not essential for tumor incidence and growth but are important in
      regulating metastasis formation.

PMID- 11956085
TI  - Tumor immunity within the central nervous system stimulated by recombinant
      Listeria monocytogenes vaccination.
AB  - Tumors arising within the central nervous system (CNS) present the immune system
      with a challenging target, given the heterogeneous nature of these neoplasms and
      their location within an "immunologically privileged" site. We used the
      lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) as a pseudotumor
      antigen to investigate recombinant Listeria monocytogenes as a tumor vaccine
      against s.c. and intracerebral challenges with a NP-expressing glioma, 9L-NP.
      Using Fischer 344 rats, we demonstrate that vaccination with recombinant L.
      monocytogenes-NP stimulates protection against s.c., but not intracerebral, 9L-NP
      tumor challenge in an antigen-specific, CD8(+) T-cell-dependent manner. After
      s.c. tumor rejection, enhanced antitumor immunity is achieved via epitope
      spreading that permits complete resistance against lethal intracerebral challenge
      with 9L-NP and with the untransfected parental 9L tumor. Unlike the CD8(+)
      dependent immune responses against s.c. 9L-NP tumors, this expanded intracerebral
      immunity against endogenous tumor-associated antigens is dependent on both CD4(+)
      and CD8(+) T cells. Taken together, these results demonstrate that the mechanisms
      of tumor immunity within the brain are different from those elicited against non
      CNS tumors. Furthermore, vaccination approaches exploiting the concept of epitope
      spreading may enhance the efficacy of antitumor immune responses within the
      immunologically privileged CNS, potentially mediating tumor cell killing through
      both CD4(+)- and CD8(+)-dependent effector pathways.

PMID- 11956086
TI  - A mutation hot spot in the Bcrp1 (Abcg2) multidrug transporter in mouse cell
      lines selected for Doxorubicin resistance.
AB  - The recent identification of mutations at arginine 482 (R482) in human Breast
      Cancer Resistance Protein (BCRP) in two drug-selected cell lines largely explains
      some discrepancies observed in the cross-resistance profiles of human cell lines
      overexpressing this multidrug transporter. We find that each of three mouse cell
      lines independently selected for resistance to the anthracycline doxorubicin also
      acquired mutations in the cognate mouse transporter Bcrp1 exclusively at R482.
      Although the mouse Bcrp1 amino acid substitutions (M or S) are distinct from
      those seen in the human cell lines (G or T), they all have similar consequences:
      (a) greater resistance to anthracyclines (and bisantrene); (b) relatively lower
      resistance to topotecan; (c) greatly enhanced efflux of the dye rhodamine 123.
      The ready selection of R482X mutations seen in vitro might also occur in tumors
      treated with anthracyclines. Thus, it is noteworthy that the efficacy of Bcrp1
      inhibitors applicable in vivo was not markedly affected by the presence of the
      mutations. We found that the Bcrp1 mutations all occurred after previous
      amplification and overexpression of the wild-type gene under doxorubicin
      selection; wild-type Bcrp1 is evidently able to mediate substantial resistance to
      anthracyclines, and this was confirmed in Bcrp1-transduced cell lines. These
      observations emphasize the general importance of the arginine at amino acid 482
      for substrate specificity of the transporter, while reminding us that unmutated
      Bcrp1 remains a potential source of resistance to anthracyclines and a potential
      factor in anthracycline pharmacokinetics. The same is most likely true of human
      BCRP, given its profound similarities to mouse Bcrp1.

PMID- 11956087
TI  - S-3-Amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell
      neoplasias in mice.
AB  - Thalidomide has recently been shown to be useful in the treatment of multiple
      myeloma and may also be useful in the treatment of other hematological
      malignancies. We have identified a new derivative of thalidomide, S-3-[3-amino
      phthalimido]-glutarimide (S-3APG) with dual activity against B-cell neoplasias. S
      3APG was able to directly inhibit the proliferation of myeloma and Burkitt's
      lymphoma cell lines in vitro without showing toxicity to normal bone marrow
      stromal cells or hematopoietic progenitor cells. In vivo, S-3APG treatment of
      drug resistant myeloma cell tumors in mice was able to produce complete and
      sustained regressions without any observed toxicity. Additionally, S-3APG induced
      complete regressions of Burkitt's lymphoma cell tumors. Furthermore, S-3APG
      inhibited angiogenesis more potently than thalidomide in the murine corneal
      micropocket model. We conclude that S-3APG is a powerful anti-myeloma and anti-B
      cell-lymphoma agent that has both antiproliferative and antiangiogenic effects.

PMID- 11956088
TI  - Potent systemic antitumor activity from an oncolytic herpes simplex virus of
      syncytial phenotype.
AB  - Conditionally replicating (oncolytic) viruses, which selectively replicate in
      tumor cells but not in normal cells, show great promise as antitumor agents for
      cancer therapy. The principal antitumor activity of these viruses derives from
      their replication within tumor cells, which results in cell destruction and the
      production of progeny virions that can spread to adjacent tumor cells. However,
      one potential limitation of this approach is that viral gene deletions conferring
      tumor selectivity also result frequently in reduced potency of the virus in
      tumors. Therefore, strategies designed to enhance the potency of current
      oncolytic viruses will likely increase their chance of clinical success. Here we
      report the construction of an oncolytic herpes simplex virus (HSV) of which the
      infection also causes strong cell membrane fusion (syncytial formation). In vitro
      characterization on a variety of human tumor cells of different tissue origins
      showed that the plaques from this virus (Fu-10) are phenotypically unique and are
      significantly larger than those from the parental G207 virus, a well
      characterized oncolytic HSV lacking fusogenic function. Furthermore, the
      syncytial formation caused by this virus depended on HSV replication, indicating
      that cell membrane fusion will only occur in dividing cells (such as tumor cells)
      where the virus can undergo a full infection cycle but not in normal cells where
      the viral replication is restricted. Systemic administration of Fu-10 into mice
      with established lung metastatic breast cancer resulted in a dramatic therapeutic
      effect. These studies demonstrate that incorporation of fusogenic function into
      an oncolytic virus can significantly increase the potency of viral oncolysis;
      this may lead to an enhanced clinical performance, especially in late-stage
      cancer patients.

PMID- 11956089
TI  - Uridine phosphorylase (-/-) murine embryonic stem cells clarify the key role of
      this enzyme in the regulation of the pyrimidine salvage pathway and in the
      activation of fluoropyrimidines.
AB  - We have reported the elevation of uridine phosphorylase (UPase) in many solid
      tumors and the presence of a variant phosphorolytic activity in breast cancer
      tissues (M. Liu et al., Cancer Res., 58: 5418-5424, 1998). To better understand
      the biological and pharmacological significance of these findings, we have
      developed an UPase gene knockout embryonic stem (ES) cell model by specific gene
      targeting techniques. In this cellular model, we establish the critical role of
      UPase as an important anabolic enzyme in 5-fluorouracil (5-FU) activation and
      pyrimidine salvage pathway regulation. It has long been known that UPase
      regulates the plasma concentration of uridine; however, little is known of the
      role of UPase in the activation and metabolism of 5-FU and its derivatives,
      mainly because of the lack of an appropriate model system. The experimental data
      indicate that the disruption of UPase activity in murine ES cells leads to a 10
      fold increase in 5-FU IC(50) and a 2-3-fold reduction in its incorporation into
      nucleic acids, whereas no differences in toxicity is seen with other pyrimidine
      nucleoside analogues such as 5-fluorouridine, 2'-deoxy-5-fluorouridine, and 1
      beta-D-arabinofuranosylcytosine compared with WT (wild-type) ES cells.
      Benzylacyclouridine can specifically prevent the WT ES cells from the sensitivity
      of 5-FU. Our data also shows the effect of UPase on the cytotoxicity of 5'-deoxy
      5-fluorouridine (5'DFUR), a 5-FU prodrug. The IC(50) is increased almost 16-fold
      in the knockout cells compared with the wild type cells, demonstrating the role
      of UPase in catalyzing the conversion of 5'DFUR to 5-FU. These findings
      additionally elucidate the tumor-specific selectivity of capecitabine, the oral
      fluoropyrimidine prodrug approved for the treatment of metastatic breast and
      colorectal cancers. Not only do the knockout cells present a decreased
      incorporation of 5-FU into nucleic acids but also an increased reliance on the
      pyrimidine salvage pathway. The reduced dependence of UPase knockout cells on the
      pyrimidine de novo synthesis is reflected in the apparent resistance to
      phosphonacetyl-L-aspartic acid, a specific inhibitor of pyrimidine pathway, with
      a 5-fold elevation in its IC(50) in UPase-nullified cells compared with WT. In
      summary, we have successfully generated an UPase gene knockout cell model that
      presents reduced sensitivity to 5-FU, 5'DFUR, and phosphonacetyl-L-aspartic acid,
      although it does not affect the basic cellular physiology under normal tissue
      culture conditions. Considering the role of UPase in 5-FU metabolism and the
      elevated expression of this protein in cancer cells compared with paired normal
      tissues, additional investigation should be warranted to firmly establish the
      clinical role of UPase in the tumor selective activation of 5-FU and
      capecitabine.

PMID- 11956090
TI  - Inhibition of radiation-induced nuclear factor-kappaB activation by an anti-Ras
      single-chain antibody fragment: lack of involvement in radiosensitization.
AB  - We have shown previously that the transduction of a number of human tumor cell
      lines with an adenovirus (AV1Y28) expressing a single-chain antibody fragment
      (scFv) directed against Ras proteins results in radiosensitization. Because Ras
      is involved in the regulation of a number of transcription factors, we have
      determined the effects of this adenovirus on the activation of nuclear factor
      kappaB (NF-kappaB), a radiation-responsive transcription factor associated with
      cell survival. In U251 human glioma cells, radiation-induced NF-kappaB was
      significantly attenuated by prior transduction of the anti-Ras scFv adenovirus.
      This effect appeared to involve an inhibition of IkappaB kinase activity and
      IkappaBalpha phosphorylation. Inhibitors to the Ras effectors mitogen-activated
      protein kinase kinase, phosphatidylinositol 3-kinase, and p38, however, did not
      reduce radiation-induced NF-kappaB. Whereas AV1Y28 inhibited NF-kappaB activation
      by hydrogen peroxide and ferricyanide, it had no effect of tumor necrosis factor
      alpha-induced NF-kappaB activation. These results are consistent with a novel Ras
      dependent, oxidant-specific signaling pathway mediating the activation of NF
      kappaB. In additional cell lines radiosensitized by AV1Y28, radiation-induced NF
      kappaB activation was also inhibited by the anti-Ras scFv, whereas in cell lines
      not radiosensitized, radiation did not activate NF-kappaB. This correlation
      suggested that AV1Y28-mediated radiosensitization involved the inhibition of
      radiation-induced NF-kappaB activation. However, inhibition of NF-kappaB
      activation via the expression of a dominant-negative form of IkappaBalpha in U251
      cells had no effect on radiation-induced cell killing and did not influence
      AV1Y28-mediated radiosensitization. Therefore, whereas AV1Y28 inhibits radiation
      induced NF-kappaB activation, this process does not appear to play a direct role
      in its radiosensitizing actions.

PMID- 11956091
TI  - CPI-0004Na, a new extracellularly tumor-activated prodrug of doxorubicin: in vivo
      toxicity, activity, and tissue distribution confirm tumor cell selectivity.
AB  - The search for cancer therapies that are more selective for tumor cells and spare
      normal sensitive cells has been very active for at least 20 years. The
      extracellularly tumor-activated peptidic prodrug of doxorubicin (Dox) CPI-0004Na
      (N-succinyl-beta-alanyl-L-leucyl-L-alanyl-L-leucyl-Dox) is potentially such a
      treatment. Here, we report the results of lethality studies performed with this
      compound in the mouse, showing that it is up to 4.6 times less toxic than Dox.HCl
      by the i.v. route and up to 16.2 times after i.p. administration.
      Pharmacokinetics and tissue distribution data indicate that this reduced toxicity
      is attributable to a lower uptake of Dox in normal tissues after treatment with
      CPI-0004Na than after the administration of an equimolar dose of Dox.HCl. For
      example, heart exposure to Dox is reduced >10-fold. Because of this reduced
      toxicity, higher doses of CPI-0004Na than of the parent drug could be used to
      treat nude mice bearing s.c. human breast (MCF-7/6) and colon (LS-174-T and CXF
      280/10) tumors. In all three models, the prodrug showed a much improved efficacy
      as compared with Dox.HCl. Particularly, LS-174-T tumors that do not respond to
      Dox were inhibited by 68% after treatment with CPI-0004Na. Tissue distribution
      studies performed with MCF-7/6 tumor-bearing nude mice and comparing CPI-0004Na
      and Dox.HCl confirmed that the improved activity of the prodrug is actually the
      result of selective generation and uptake of Dox at the tumor site. Dox levels in
      tumor tissue were 2-fold higher after treatment with CPI-0004Na than after
      treatment with an equimolar dose of Dox.HCl, whereas normal tissue levels were
      reduced 1.4-29-fold.

PMID- 11956092
TI  - Brostallicin, a novel anticancer agent whose activity is enhanced upon binding to
      glutathione.
AB  - Brostallicin (PNU-166196) is a synthetic alpha-bromoacrylic, second-generation
      DNA minor groove binder structurally related to distamycin A, presently in Phase
      II trials in Europe and the United States. The compound shows broad antitumor
      activity in preclinical models and dramatically reduced in vitro myelotoxicity in
      human hematopoietic progenitor cells compared with that of other minor groove
      binders. Brostallicin showed a 3-fold higher activity in melphalan-resistant
      L1210 murine leukemia cells than in the parental line (IC(50) = 0.46 and 1.45
      ng/ml, respectively) under conditions in which the cytotoxicity of conventional
      antitumor agents was either unaffected or reduced. This melphalan-resistant cell
      line has increased levels of glutathione (GSH) in comparison with the parental
      cells. Conversely, GSH depletion by buthionine sulfoximine in a human ovarian
      carcinoma cell line (A2780) significantly decreased both the cytotoxic and the
      proapoptotic effects of brostallicin. In one experiment, human glutathione S
      transferase pi (GST-pi) cDNA was transfected into A2780 cells, and four clones of
      A2780 with different expression levels of GST-pi were generated (i.e., two clones
      with high and two clones with low GST-pi expression). A 2-3-fold increase in GST
      pi levels resulted in a 2-3-fold increase in cytotoxic activity of brostallicin.
      Similar results were obtained for GST-pi-transfected human breast carcinoma cells
      (MCF-7). Brostallicin showed 5.8-fold increased cytotoxicity in GST-pi
      transfected versus empty vector-transfected cells with low GST-pi expression. In
      an in vivo experiment, A2780 clones were implanted into nude mice. The antitumor
      activity of brostallicin was higher in the GST-pi-overexpressing tumors without
      increased toxicity. Regarding the mechanism of action, brostallicin interacts
      reversibly with the DNA minor groove TA-rich sequences but appears unreactive in
      classical in vitro DNA alkylation assays. We speculated that an intracellular
      reactive nucleophilic species, e.g., GSH, could react with the alpha
      bromoacrylamide moiety functions. Experiments on the interaction with plasmid DNA
      showed a change of the DNA topology from supercoiled to circular form (nicking)
      in the presence of GSH, whereas no change was found in its absence. In vitro
      incubations of brostallicin were performed with the human recombinant GST
      isoenzymes A1-1, M1-1, and P1-1 (alpha, mu and pi isoenzymes, respectively) in
      the presence of GSH. The decrease in brostallicin levels was monitored in these
      incubations; the rate of loss (and therefore brostallicin metabolism) was
      significantly higher for the M1-1 and P1-1 isoenzymes than for the A1-1
      isoenzyme.

PMID- 11956093
TI  - High and selective expression of yeast cytosine deaminase under a
      carcinoembryonic antigen promoter-enhancer.
AB  - Yeast cytosine deaminase (yCD)-based gene therapy offers the potential for
      selective production of the cytotoxic and radiosensitizing drug 5-fluorouracil (5
      FU) from the benign prodrug 5-fluorocytosine within colorectal cancers. Although
      previous attempts to target therapy to colorectal cancer using the
      carcinoembryonic antigen (CEA) promoter have demonstrated specificity, this has
      been achieved at the cost of 10- to 300-fold loss in activity compared with
      strong but nonspecific rous sarcoma virus (RSV) or cytomegalovirus promoters. We
      developed a highly specific and active gene transfer method for colorectal cancer
      using CEA under control of a promoter-enhancer. We compared the RSV promoter
      derived with the CEA promoter-enhancer-derived transgene expression in 10
      different cell lines with differing CEA status. We found that the transgene
      expression resulting from both transient transfection and adenoviral infection
      with the CEA promoter-enhancer was as strong as the RSV promoter while
      maintaining specificity for CEA-producing cell lines. For instance, when we
      compared yCD expression between LoVo (CEA+) and human fibroblast (CEA-), we found
      a 30-fold-increased yCD expression in LoVo cells from CEA-enhancer adenovirus
      although there was no difference in the yCD expression between the cell lines
      when infected with RSV/yCD virus. This specificity was also achieved while
      maintaining a higher yCD enzyme activity than we obtained with RSV/yCD adenovirus
      in an HT-29 intrahepatic tumor model. We then compared the response of HT-29
      xenografts to treatment with 5-fluorocytosine and yCD adenovirus driven by either
      the RSV or the CEA promoter-enhancer and found similar tumor growth inhibition.
      These findings suggest that the CEA promoter-enhancer strategy confers
      specificity while preserving activity and is worth exploring in additional animal
      and, potentially, clinical trials.

PMID- 11956094
TI  - Selective cyclooxygenase (COX)-1 or COX-2 inhibitors control metastatic disease
      in a murine model of breast cancer.
AB  - Using a highly metastatic mammary tumor cell line that expresses both
      cyclooxygenase (COX) isoforms, we now show that oral administration of either a
      selective COX-2 inhibitor (celecoxib) or a selective COX-1 inhibitor (SC560) to
      mice with established tumors results in significant inhibition of tumor growth.
      Administration of the dual inhibitor, indomethacin, leads to even better growth
      control. Metastatic capacity is also reduced by treatment of tumor-bearing mice
      with either COX-1 or COX-2 selective inhibitors. Pretreatment of tumor cells with
      COX inhibitors also reduces metastatic success, indicating that tumor cells may
      be a direct target of action by COX inhibitors. Growth of a second cell line,
      which does not express COX-2 in vivo, is also reduced by celecoxib, implicating
      both COX-dependent and COX-independent mechanisms.

PMID- 11956095
TI  - Apoptotic pancreatic tumor cells are superior to cell lysates in promoting cross
      priming of cytotoxic T cells and activate NK and gammadelta T cells.
AB  - Tumor vaccines using dendritic cells (DCs) have been shown to induce antitumor
      CTL responses. The choice of the tumor antigen preparation used for DC loading is
      still an unresolved issue. We compared DCs pulsed with cell lysates, whole
      apoptotic tumor cells or their supernatants of the HLA-A2(+) human pancreatic
      carcinoma cell line Panc-1 for their capacity to activate T cells. Monocyte
      derived DCs from HLA-A2(+) donors were pulsed with tumor antigen, matured
      subsequently, and cocultured with autologeous peripheral blood mononuclear cells.
      After three weekly restimulations with DCs, T-cell activation was assessed by
      intracellular IFN-gamma staining and cytotoxicity assays. Compared with lysate,
      pulsing DCs with the supernatant of apoptotic tumor cells induced a higher
      frequency of activated CTLs and T-helper cells, as well as an enhanced MHC class
      I-restricted tumor cell lysis. No activation of natural killer (NK) or gammadelta
      T cells was detected. Pulsing DCs with whole apoptotic tumor cells induced an
      even more pronounced lytic effect. However, in this case, MHC class-I blocking
      was only partially effective, and unrelated cell lines were also killed. IFN
      gamma staining revealed activation of CTLs and T-helper cells, as well as NK and
      gammadelta T cells. Trans-well cultures of NK cells, apoptotic tumor cells, and
      DCs showed that NK cell activation was dependent on direct cell-to-cell contact
      with tumor cells and the presence of interleukin-12 produced by DCs. These
      results indicate that the choice of antigen preparation is a critical determinant
      in the induction of antitumor immunity. Tumor vaccines consisting of DCs and
      apoptotic tumor cells may be able to activate CTLs, as well as effector cells of
      the innate immune system.

PMID- 11956096
TI  - Gemcitabine exerts a selective effect on the humoral immune response:
      implications for combination chemo-immunotherapy.
AB  - Most cytotoxic drugs have gross effects on the immune system, such as neutropenia
      and lymphopenia. However, their effects on tumor-specific immune responses are
      unknown. Gemcitabine is a nucleoside analogue that is frequently used to treat
      non-small cell lung cancer. It is also active in other malignancies, either alone
      or in combination with cisplatin. Here, we investigate its effects on antigen
      specific antitumor immunity using a murine tumor cell line transfected to express
      influenza virus hemagglutinin (HA). CD4(+), CD8(+), and B220(+) lymphocyte
      numbers all decreased during chemotherapy (120 microg/g, i.p., every third day
      for five doses), but B cells were selectively depleted. Gemcitabine induced a
      profound suppression of the IgG antibody response to HA, and this was unrelated
      to tumor size. In contrast, in vitro T-lymphocyte recall responses to the class I
      and class II-restricted dominant peptide epitopes of HA were enhanced in tumor
      bearing, gemcitabine-treated mice. We found that gemcitabine was >2-fold more
      potent in its ability to inhibit B-lymphocyte proliferation compared with T
      lymphocyte proliferation. Thus, gemcitabine does not appear to be detrimental to
      specific antitumor cellular immunity and may be useful in combination chemo
      immunotherapy protocols. In contrast, vaccination protocols requiring a humoral
      immune response for maximal efficacy may be compromised in patients treated with
      gemcitabine.

PMID- 11956097
TI  - New insights into testicular germ cell tumorigenesis from gene expression
      profiling.
AB  - We have shown recently that about half of the human TGCTs(3) reveal DNA copy
      number increases affecting two distinct regions on chromosome arm 17q. To
      identify potential target genes with elevated expressions attributable to the
      extra copies, we constructed a cDNA microarray containing 636 genes and expressed
      sequence tags from chromosome 17. The expression patterns of 14 TGCTs, 1
      carcinoma in situ, and 3 normal testis samples were examined, all with known
      chromosome 17 copy numbers. The growth factor receptor-bound protein 7 (GRB7) and
      junction plakoglobin (JUP) were the two most highly overexpressed genes in the
      TGCTs. GRB7 is tightly linked to ERBB2 and is coamplified and coexpressed with
      this gene in several cancer types. Interestingly, the expression levels of ERBB2
      were not elevated in the TGCTs, suggesting that GRB7 might be the target for the
      increased DNA copy number in TGCTs. Because of the limited knowledge of altered
      gene expression in the development of TGCTs, we also examined the expression
      levels of 512 additional genes located throughout the genome. Several genes novel
      to testicular tumorigenesis were consistently up- or down-regulated, including
      POV1, MYCL1, MYBL2, MXI1, and DNMT2. Additionally, overexpression of the proto
      oncogenes CCND2 and MYCN were confirmed from the literature. The overexpressions
      were for some of the target genes closely associated to either seminoma or
      nonseminoma TGCTs, and hierarchical cluster analysis of the gene expression data
      effectively distinguished among the known histological subtypes. In summary, this
      focused functional genomic characterization of TGCTs has lead to the
      identification of new gene targets associated with a common genomic rearrangement
      as well as other genes with potential importance to testicular tumorigenesis.

PMID- 11956098
TI  - Detection of chromosomal aneuploidies and gene copy number changes in fine needle
      aspirates is a specific, sensitive, and objective genetic test for the diagnosis
      of breast cancer.
AB  - Fine needle aspiration cytology is central to the evaluation of clinically or
      mammographically detected suspicious lesions of the breast. On the basis of
      results from studies of >500 breast cancers by comparative genomic hybridization
      we have developed protocols and designed probe sets that allow one to visualize
      recurrent chromosomal aneuploidies, amplification of oncogenes, and deletion of
      tumor suppressor genes directly in cytological preparations using multicolor
      fluorescence in situ hybridization. The fluorescence in situ hybridization probes
      are specific for chromosome arm 1q, the c-MYC and HER2 oncogenes, the tumor
      suppressor gene p53 and, as controls for chromosome ploidy of each cell, the
      centromeres of chromosomes 8, 10, and 17. Application of these diagnostic
      mixtures to 20 invasive breast cancers, 7 mastopathias, and 2 fibroadenomas
      demonstrates that a highly sensitive, specific, and objective diagnosis of breast
      cancer is now possible on cytological preparations obtained by minimally invasive
      fine needle aspiration.

PMID- 11956099
TI  - Aberrant promoter methylation in bronchial epithelium and sputum from current and
      former smokers.
AB  - Recent studies from our laboratory suggest that gene-specific methylation changes
      in sputum could be good intermediate markers for the early detection of lung
      cancer and defining the efficacy of chemopreventive interventions. The purpose of
      our study was to determine the prevalence for aberrant promoter methylation of
      the p16, O(6)-methylguanine-DNA methyltransferase (MGMT), death-associated
      protein (DAP) kinase, and Ras effector homologue (RASSFIA) genes in nonmalignant
      bronchial epithelial cells from current and former smokers in a hospital-based,
      case control study of lung cancer. The relationship between loss of
      heterozygosity, at 9p and p16 methylation in bronchial epithelium and the
      prevalence for methylation of these four genes in sputum from cancer-free,
      current and former smokers were also determined. Aberrant promoter methylation of
      p16 was seen in at least one bronchial epithelial site from 44% of cases and
      controls. Methylation of the DAP kinase gene was seen in only 1 site from 5 cases
      and 4 controls, whereas methylation of the RASSFIA was not detected in the
      bronchial epithelium. Promoter methylation for p16 and DAP kinase was seen as
      frequently in bronchial epithelium from current smokers as from former smokers.
      No promoter methylation of these genes was detected in bronchial epithelium from
      never-smokers. Methylation of the p16 gene was detected in sputum from 23 of 66
      controls. DAP kinase gene promoter methylation was also seen in sputum from 16
      controls, and 8 of these subjects were positive for p16 methylation. Methylation
      of the MGMT gene was seen in sputum from 9 controls, whereas RASSFIA promoter
      methylation was only seen in 2 controls. The correlation between p16 status in
      the bronchial epithelium obtained from lung lobes that did not contain the
      primary tumor and the tumor itself was examined. Seventeen of 18 tumors (94%)
      showed an absolute concordance, being either methylated in the tumor and at least
      1 bronchial epithelial site, or unmethylated in both tumor and bronchial
      epithelium. These results indicate that aberrant promoter hypermethylation of the
      p16 gene, and to a lesser extent, DAP kinase, occurs frequently in the bronchial
      epithelium of lung cancer cases and cancer-free controls and persists after
      smoking cessation. The strong association seen between p16 methylation in the
      bronchial epithelium and corresponding primary tumor substantiates that
      inactivation of this gene, although not transforming by itself, is likely
      permissive for the acquisition of additional genetic and epigenetic changes
      leading to lung cancer.

PMID- 11956101
TI  - A Helicobacter pylori restriction endonuclease-replacing gene, hrgA, is
      associated with gastric cancer in Asian strains.
AB  - The sensitivity of Helicobacter pylori chromosomal DNA to MboI digestion was
      investigated in 208 strains from several continents. Only 11 (5%) of strains were
      sensitive to MboI, and it was hypothesized that HpyIII, a type II
      restriction/modification enzyme with sequence homology to MboI, mediated the
      protection. This was confirmed by PCR analysis of the gene locus of hpyIII,
      normally composed of hpyIIIR and hpyIIIM. In all but one strain sensitive to
      MboI, no PCR product of hpyIIIR was obtained. In contrast, all strains yielded a
      product for hpyIIIM, independent of MboI phenotype. Further examination of the
      hpyIII locus in strains lacking a hpyIIIR PCR product identified a novel gene,
      hrgA, upstream of hpyIIIM. All 208 strains examined had either hpyIIIR or hrgA,
      but not both, upstream of hpyIIIM. Although hrgA has homology with a
      Campylobacter jejuni gene (Cj1602), its function is not known. In Western
      countries, hrgA was more prevalent (53%) than in Asia (25%; P < 0.0001, chi(2)).
      In Asia, hrgA was more prevalent among gastric cancer patients (18 of 43; 42%)
      than among noncancer patients (16 of 95; 17%; P = 0.001, chi(2)). All 143 Asian
      strains tested were cagA(+), but among Western strains, hrgA was more prevalent
      in cagA(+) strains (26 of 42; 62%) than in cagA(-) strains (9 of 23; 39%; P =
      0.04, chi(2)). In coculture with epithelial cells, hpyIIIR and hrgA strains did
      not show any significant differences in interleukin-8 induction and apoptosis.
      Although a direct function for hrgA in virulence could not be demonstrated, our
      data indicate that hrgA is a strain-specific gene that might be associated with
      gastric cancer among H. pylori isolates from Asian patients.

PMID- 11956100
TI  - Cell division is required for de novo methylation of CpG islands in bladder
      cancer cells.
AB  - Cell division is essential for tumor development and progression. Methylation
      mediated silencing caused by aberrant de novo methylation of CpG islands located
      in the promoter regions of growth regulatory genes occurs frequently in human
      cancers. We investigated the relationship between cell division and de novo
      methylation to determine whether de novo methylation can occur in the absence of
      cell division in cancer cells. We treated T24 bladder carcinoma cells with 5-Aza
      2'-deoxycytidine to induce a transient demethylation and then compared the timing
      and kinetics of remethylation of the p16 gene locus under conditions of either
      G(0)-G(1) growth arrest induced by serum starvation and confluence or continuous
      cell proliferation in complete medium. Variable levels of remethylation were
      detected in CpG poor regions of DNA, as well as repetitive DNA elements in the
      absence of cell division, yet no remethylation occurred at CpG islands under
      these conditions. This correlated with continuous expression of p16 protein in
      these cells. DNA methyltransferase (DNMT)1 and DNMT3b3 proteins were undetectable
      in 5-Aza-2'-deoxycytidine-treated and untreated nondividing cells, and their mRNA
      transcripts were down-regulated in these cells. Although DNMT3a mRNA levels were
      also reduced, they recovered to original levels in nondividing cells after drug
      treatment. Our results suggest that cell division is required for de novo
      methylation of CpG islands and that DNMT3a may play a role in methylating CpG
      poor regions or repetitive DNA elements outside of the S phase of the cell cycle.

PMID- 11956103
TI  - The High Mobility Group A2 gene is amplified and overexpressed in human
      prolactinomas.
AB  - Trisomy of chromosome 12 is a nonrandom chromosomal change in pituitary adenomas,
      particularly prolactinomas. This and the finding that prolactin-secreting
      pituitary adenomas develop in transgenic mice overexpressing the wild-type HMGA2
      gene (which maps to 12q14-15) prompted us to investigate HMGA2 rearrangements and
      expression in human prolactinomas. By dual-color interphase fluorescence in situ
      hybridization analysis using HMGA2-specific PACs and BACs, we found that the
      HMGA2 locus was amplified in seven of the eight prolactinoma samples examined.
      The cytogenetic manifestations of elevated HMGA2 concentrations ranged from
      simple trisomy to tetrasomy 12 and der(12) chromosomes to marker chromosomes
      bearing 12q14-15-derived regions. Reverse transcription-PCR, Western blot and
      immunohistochemical analysis showed HMGA2 overexpression in a number of
      prolactinomas bearing rearrangement of regions 12q14-15. These data suggest a
      critical role of the HMGA2 overexpression in the generation of prolactin
      secreting pituitary adenomas in humans.

PMID- 11956102
TI  - Urokinase receptor antibody can reduce tumor volume and detect the presence of
      occult tumor metastases in vivo.
AB  - The serine protease urinary plasminogen activator or urokinase (uPA), produced in
      abundance by many malignancies, plays a key role in tumor cell invasion and
      metastasis. uPA is localized within the malignant cell milieu via its cell
      surface receptor [uPA receptor (uPAR)], which is expressed by tumor and tumor
      associated cells. In the present study, we have used a syngeneic model of rat
      breast cancer to directly evaluate the role of uPAR as a diagnostic and
      therapeutic target in metastatic breast cancer. A polyclonal antibody against the
      ligand-binding NH(2)-terminal domain of rat uPAR (ruPAR) was developed. This
      antibody recognizes ruPAR by both immunofluorescence and Western blot analysis.
      Recombinant ruPAR and ruPAR IgG displaced the binding of (125)I-labeled ruPAR IgG
      to rat prostate cancer cells (Dunning R3227 Mat Ly Lu) and breast cancer cells
      (Mat B-III) overexpressing ruPAR (Mat B-III-uPAR). ruPAR IgG also blocked the
      invasive capacity of these tumor cells in a dose-dependent manner. Mat B-III-uPAR
      cells were inoculated s.c. into the mammary fat pad of syngeneic female Fischer
      rats. On day 10 after tumor cell inoculation, animals were injected with (125)I
      labeled preimmune or ruPAR IgG and then sacrificed at timed intervals. Maximum
      (125)I uptake was observed in primary tumors and in tissues commonly affected by
      tumor metastases (liver, spleen, lungs, and lymph nodes) at 12 h. Injection of
      (125)I-labeled preimmune or ruPAR IgG into normal non-tumor-bearing animals
      resulted in minimal basal levels of uPAR expression and established the
      specificity of the ruPAR IgG. Similar results were obtained by Northern blot and
      PCR analysis of mRNA isolated from tissues of normal and tumor-bearing animals.
      To evaluate the effectiveness of this antibody in tumor progression, ruPAR IgG
      (50-100 microg/day) was injected s.c. for 7 days (day 1-7) at the site of tumor
      cell inoculation (mammary fat pad), and animals were sacrificed at various time
      points for evaluation of tumor growth and metastases. Animals receiving ruPAR IgG
      showed a marked decrease in tumor growth and metastases as compared with control
      tumor-bearing animals receiving the same dose of preimmune rabbit IgG.
      Histological analysis of experimental primary tumors showed marked tumor necrosis
      that was due to increased tumor cell apoptosis as determined by terminal
      deoxynucleotidyl transferase-mediated nick end labeling assay. Together, these
      studies demonstrate the ability of anti-uPAR antibody to decrease tumor volume
      and detect the presence of microscopic occult tumor metastases in malignancies
      where uPA/uPAR play a key role in tumor progression.

PMID- 11956104
TI  - Oxytocin is a growth factor for Kaposi's sarcoma cells: evidence of endocrine
      immunological cross-talk.
AB  - Oxytocin receptors (OTRs) are expressed in numerous tissues, including human
      normal endothelium. Here we investigated the expression and biological
      significance of OTRs in Kaposi's sarcoma (KS), an intensely angioproliferative
      disease of possible vascular origin with a prominent inflammatory component.
      Immunohistochemistry and in situ hybridization studies showed OTR expression in
      tumor cells of cutaneous classic and AIDS-related KS lesions. OTR mRNA and
      protein were also detected on cultured KS-IMM spindle cells by reverse
      transcription-PCR and immunofluorescence procedures. In these cells, OTR
      expression was up-regulated by the supernatants of resting CD4+ and CD8+
      lymphocytes through a still unidentified factor. Functionality of OTRs was
      demonstrated because OT treatment of KS-IMM cells led to a significant increase
      in cell proliferation, coupled to the increase of intracellular calcium, but did
      not effect cell migration in vitro or angiogenesis in vivo. In addition, we
      demonstrated that CD4+ and CD8+ cells produce OT themselves, thus constituting an
      intralesional source of peptide. These results indicate that: (a) functioning
      OTRs are expressed in KS cells and modulated by the inflammatory counterpart of
      KS lesions; (b) via OTRs, OT stimulates KS-IMM cell proliferation and could,
      therefore, be considered a new possible relevant growth factor involved in KS
      progression; and finally (c) the evidence of OT synthesis by CD4+ and CD8+
      lymphocytes strongly suggests the existence of local endocrine-immunological
      cross-talk in Kaposi's sarcoma.

PMID- 11956105
TI  - Repair by Src kinase of function-impaired RET with multiple endocrine neoplasia
      type 2A mutation with substitutions of tyrosines in the COOH-terminal kinase
      domain for phenylalanine.
AB  - An oncogenic mutant of c-RET as a receptor-type tyrosine kinase, termed RET
      MEN2A, displays both cell-transforming activity in vivo and strong catalytic
      activity in vitro. In this study, we compared the activities of mutant RET-MEN2A
      with substitutions of each of nine tyrosines for phenylalanine (Y1062F, Y1015F,
      Y981F, Y952F, Y928F, Y905F, Y900F, Y864F, and Y826F), which had been transfected
      into NIH 3T3 cells. In RET-MEN2A with the Y905F mutation, the cell-transforming
      activity was drastically reduced with a great reduction in the in vitro catalytic
      activity. Unexpectedly, we found that in vitro kinase activity was severely
      impaired in RET-MEN2A with Y981F, Y952F, or Y928F mutation, which displayed near
      normal cell-transforming activity and only a partially impaired tyrosine
      phosphorylation level in vivo. Phosphoamino acid analysis actually demonstrated
      some increase in phosphotyrosine in the Y905F mutant but no or barely detectable
      increase in the Y981F, Y952F, or Y928F mutant after incubation for in vitro
      kinase assay. This suggested a crucial role of the Y981/Y952/Y928-linked
      structural integrity of the COOH end of the catalytic domain of RET in starting
      Y905 autophosphorylation. Interestingly, the apparent defect in intrinsic kinase
      activity in vitro in the Y981F, Y952F, or Y928F mutant, but not the reduction in
      activity in the Y905F mutant, could be partially repaired or restored by c-Src
      or, more extensively, by v-Src, which promoted Y905 phosphorylation in trans. A
      complex was shown to be formed between v-Src and RET-MEN2A through association of
      both with a cholesterol-rich membrane microdomain known as "a raft," possibly for
      efficient contact of submembranous domains of Src and RET to promote
      phosphorylation of Y905 of the latter. Finally, endogenous c-Src was shown to
      promote Y905 phosphorylation of the Y981F mutant in vivo. These results reveal a
      novel Src kinase-mediated repair mechanism of otherwise function-impaired mutant
      RET kinases.

PMID- 11956106
TI  - Protein kinase cepsilon has the potential to advance the recurrence of human
      prostate cancer.
AB  - Prostatic epithelial cells that are capable of surviving in the absence of
      androgenic steroids were found to express protein kinase Cepsilon (PKCepsilon),
      an oncogenic protein capable of promoting autocrine cell-signaling events. Gene
      transfer experiments demonstrated that PKCepsilon overexpression was sufficient
      to transform androgen-dependent LNCaP cells into an androgen-independent variant
      that rapidly initiated tumor growth in vivo in both intact and castrated male
      nude mice. This transformation was associated with an accelerated rate of
      androgen-independent LNCaP cell proliferation, resistance to apoptosis,
      hyperphosphorylation of the mitogen-activated protein kinase extracellular signal
      regulated kinase and transcriptional repressor protein retinoblastoma, and
      increased expression of E2F-1 and other 5'-cap-dependent mRNAs, including the
      G(1) cyclins, c-myc, and caveolin-1. Coimmunoprecipitation experiments indicated
      that PKCepsilon was associated with members of the extracellular signal-regulated
      kinase signaling cascade and the scaffolding protein caveolin-1. Caveolin-1,
      produced by LNCaP cells overexpressing PKCepsilon, was released into the medium,
      possibly through a Golgi-independent route, and significant growth inhibition was
      observed when these cells were cultured in the presence of an anti-caveolin-1
      antiserum. Finally, antisense experiments established that endogenous PKCepsilon
      plays an important role in regulating the growth and survival of androgen
      independent prostate cancer cells. This study provides several independent lines
      of evidence supporting the hypothesis that PKCepsilon expression may be
      sufficient to maintain prostate cancer growth and survival after androgen
      ablation.

PMID- 11956108
TI  - Identification of nuclear matrix protein alterations associated with human colon
      cancer.
AB  - The early diagnosis of colorectal cancer and the early detection of recurrence
      are central to effective treatment, as prognosis is directly related to the stage
      of the disease. When colorectal cancer is diagnosed at an early, localized stage,
      5-year survival is 90%. With regional lymph node metastases, survival drops to 45
      60%, and with distant metastases, 5-year survival is <5%. Development of tumor
      markers that can detect colon cancer at an early stage should have a major impact
      in mortality from this disease. The nuclear matrix is the structural scaffolding
      of the nucleus, and specific nuclear matrix proteins (NMPs) have been identified
      as an oncological "fingerprint" for bladder, renal, and prostate cancers. We have
      successfully used this approach to develop an immunoassay that detected bladder
      cancer early in a clinical trial with a sensitivity of 96.4% and a specificity of
      100%. The objective of the present study was to identify the existence of a
      specific NMP fingerprint for human colon cancer, using high-resolution, two
      dimensional gel electrophoresis, and thereby identify unique human colon cancer
      NMPs. Ten matched colon cancer and adjacent normal samples and 4 normal donor
      samples were analyzed. Analysis of multiple gels for each sample identified four
      proteins present in all tumor samples that were not present in the matched normal
      adjacent and normal colon tissue and six proteins present only in normal adjacent
      and normal colon tissue. Additionally, two proteins were found in all cancer and
      normal tissues, but not in the normal adjacent tissue. Data provided here
      demonstrate that examination of the nuclear matrix composition allows
      differentiation of colon cancer tissue from normal adjacent and normal colon
      tissue. Development of an assay to detect these specific NMPs by examining
      tissue, serum, and stool specimens is a promising modality for early detection of
      colorectal cancer. In addition, the functional characterization of these proteins
      and their early detection through the generation of NMP antibodies could
      significantly impact on the understanding of cancer progression and its
      diagnosis.

PMID- 11956110
TI  - Evaluation and management of patients with aortic stenosis.

PMID- 11956107
TI  - The synthetic retinoid CD437 selectively induces apoptosis in human lung cancer
      cells while sparing normal human lung epithelial cells.
AB  - The synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene
      carboxylic acid (CD437) induces apoptosis in a variety of cancer cells including
      lung cancer cells. Our previous studies have demonstrated that cancer cells with
      wild-type p53 are more sensitive to CD437 than those having mutant p53, although
      CD437 can induce both p53-dependent and -independent apoptosis. Because normal
      human lung epithelial cells have wild-type p53, the question arose as to whether
      they are also sensitive to CD437-induced apoptosis. To address this question, we
      compared and contrasted the effects of CD437 on apoptosis induction and the
      expression of several p53-regulated apoptosis-related genes between normal human
      lung epithelial cells and human lung cancer cells containing wild-type p53. CD437
      induced apoptosis as evidenced by apoptotic morphological changes, increased DNA
      fragmentation, and activation of caspase cascades in two lung cancer cell lines
      but not in two normal human lung epithelial cells. CD437 selectively increased
      the p53 protein level and concomitantly induced the expression of several p53
      regulated apoptosis-related genes including Bax, Fas, DR4, and DR5 only in the
      two lung cancer cell lines. Furthermore, the normal lung epithelial cells, which
      expressed constitutively higher levels of two antiapoptotic decoy receptors DcR1
      and DcR2 than lung cancer cells, exhibited an increase in the expression of these
      receptors after CD437 treatment, whereas no increase was detected in lung cancer
      cells. These results predict a differential effect of CD437 on tumor and normal
      cells in vivo and strongly suggest that CD437 may be a useful agent for
      chemoprevention and/or treatment of human cancer, especially lung cancer.

PMID- 11956111
TI  - Clinical research skills development: a new approach.

PMID- 11956112
TI  - The "unsympathetic" nervous system of heart failure.

PMID- 11956113
TI  - Statin prevents tissue factor expression in human endothelial cells: role of
      Rho/Rho-kinase and Akt pathways.
AB  - BACKGROUND: Tissue factor plays a pivotal role in thrombus formation in acute
      coronary syndromes. However, the regulatory mechanisms underlying tissue factor
      expression are poorly understood. Statins are effective in patients with acute
      coronary syndromes. Hence, the aim of this study was to clarify in human
      endothelial cells the signaling pathways of thrombin-induced tissue factor
      expression and potential inhibitory effects of statins. METHODS AND RESULTS: In
      human aortic endothelial cells, simvastatin prevented tissue factor induction by
      thrombin (4 U/mL) in a concentration-dependent manner. The increase in tissue
      factor activity on the cell surface was also blocked by simvastatin. Simvastatin
      also prevented the upregulation of tissue factor expression and activity in human
      aortic smooth muscle cells. Mevalonate (100 micromol/L) reversed the inhibitory
      effect of simvastatin on tissue factor expression. Thrombin induced rapid
      activation of Rho A and p38 MAP kinase. The Rho-kinase inhibitor Y-27632 and the
      p38 MAP kinase inhibitor SB203580 prevented tissue factor induction. Akt was
      dephosphorylated by thrombin; the phosphoinositol 3-kinase inhibitor wortmannin
      enhanced its dephosphorylation as well as thrombin-induced tissue factor
      expression. Simvastatin prevented thrombin-induced Rho A activation but not p38
      MAP kinase activation. Akt dephosphorylation by thrombin was blocked by both
      simvastatin and Y-27632. CONCLUSIONS: Endothelial tissue factor induction by
      thrombin is regulated by Rho/Rho-kinase, Akt, and p38 MAP kinase. Simvastatin
      prevents its induction through inhibition of Rho/Rho-kinase and activation of
      Akt. These findings provide new insights into the action of statins in acute
      coronary syndromes.

PMID- 11956114
TI  - Multimarker approach to risk stratification in non-ST elevation acute coronary
      syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type
      natriuretic peptide.
AB  - BACKGROUND: In patients with acute coronary syndromes (ACS), troponin I (TnI), C
      reactive protein (CRP), and B-type natriuretic peptide (BNP) each predict adverse
      cardiac events. Little is known, however, about the utility of these biomarkers
      in combination. METHODS AND RESULTS: Baseline measurements of TnI, CRP, and BNP
      were performed in 450 patients in OPUS-TIMI 16. Elevations in TnI, CRP, and BNP
      each were independent predictors of the composite of death, myocardial infarction
      (MI), or congestive heart failure (CHF). When patients were categorized on the
      basis of the number of elevated biomarkers at presentation, there was a near
      doubling of the mortality risk for each additional biomarker that was elevated
      (P=0.01). Similar relationships existed for the endpoints of MI, CHF, and the
      composite, both at 30 days and through 10 months. In a validation cohort of 1635
      patients in TACTICS-TIMI 18, the number of elevated biomarkers remained a
      significant predictor of the composite endpoint after adjustment for known
      clinical predictors: patients with one, two, and three elevated biomarkers had a
      2.1- (P=0.006), 3.1- (P<0.001), and 3.7- (P=0.001) fold increase in the risk of
      death, MI, or CHF by 6 months. CONCLUSIONS: Troponin, CRP, and BNP each provide
      unique prognostic information in patients with ACS. A simple multimarker strategy
      that categorizes patients based on the number of elevated biomarkers at
      presentation allows risk stratification over a broad range of short- and long
      term major cardiac events.

PMID- 11956115
TI  - Noninvasive imaging of myocardial reperfusion injury using leukocyte-targeted
      contrast echocardiography.
AB  - BACKGROUND: We hypothesized that myocardial contrast echocardiography (MCE) with
      leukocyte-targeted microbubbles could temporally and spatially characterize the
      severity of postischemic myocardial inflammation. METHODS AND RESULTS: In 9 open
      chest dogs, either the left anterior descending or left circumflex coronary
      artery was occluded for 90 minutes (n=6), while the remaining dogs served as non
      ischemic controls. During occlusion, MCE was performed to determine the risk area
      (RA) and regions supplied by collateral flow. Myocardial inflammation was
      assessed 5, 60, and 120 minutes after reflow by MCE imaging of leukocyte-targeted
      (phosphatidylserine-containing) lipid microbubbles. The spatial extent and
      severity of inflammation were also assessed by radionuclide imaging of the
      neutrophil-avid tracer 99mTcRP517 and tissue myeloperoxidase activity. Early
      after reflow, MCE detected inflammation throughout the entire risk area, the
      extent of which decreased over time due to reduced signal in collateral-supplied
      regions. The spatial extent of inflammation late after reflow was similar for MCE
      and radionuclide imaging. The severity of inflammation in the infarct zone, the
      noninfarcted risk area, and collateral-supplied territories determined by
      quantitative MCE correlated well with myeloperoxidase activity (r=0.81).
      CONCLUSIONS: MCE with leukocyte-targeted microbubbles can temporally assess the
      severity and extent of postischemic myocardial inflammation and could be used to
      evaluate new treatment strategies designed to limit inflammation in acute
      coronary syndromes.

PMID- 11956116
TI  - Patterns of myocardial endothelin-1 expression and outcome after cardiac
      transplantation.
AB  - BACKGROUND: Endothelin-1 (ET-1), a potent vasoconstrictor, is released in
      response to several inflammatory cytokines after heart transplantation. The
      present study correlated patterns of myocardial ET-1 expression in heart biopsies
      with acute rejection, post-transplantation ischemic injury, and subsequent
      development of coronary vasculopathy. METHODS AND RESULTS: Patterns of myocardial
      ET-1 expression were evaluated in 47 heart transplant recipients at 3 months
      after transplant. Transplant vasculopathy was documented by coronary angiography
      at 2 years after transplant. Expression of ET-1 was tabulated for both blood
      vessels and the interstitium. Vascular ET-1 expression was positive in 7/17 (41%)
      of patients with greater than grade 2 (International Society Heart Lung
      Transplant) rejection compared with 3/30 (10%) of patients with grade 0 and grade
      1A rejection (P=0.02). Compared with patients with negative interstitial ET-1
      expression (n=22), patients with positive interstitial ET-1 expression (n=25) had
      higher incidence of post-transplantation ischemic injury (52% versus 9%,
      P=0.002), lower mean episodes of acute rejection (> or = grade 2) during the
      first 3 months of transplant (1.09+/-0.66 versus 1.86+/-1.6, P=0.048), and more
      common vasculopathy at 2 years (50% versus 15%, P=0.02), and they tended to have
      worse survival (83.2% versus 100%, P=0.058). CONCLUSIONS: Vascular ET-1
      expression is likely to be associated with acute rejection. Interstitial ET-1
      expression, however, is more likely to be associated with post-transplantation
      ischemic injury and subsequent development of coronary vasculopathy.

PMID- 11956117
TI  - Artifact-free in-stent lumen visualization by standard magnetic resonance
      angiography using a new metallic magnetic resonance imaging stent.
AB  - BACKGROUND: Metallic stents cause susceptibility and radiofrequency artifacts on
      MR images, which, up to now, have not allowed for complete visualization of the
      stent lumen by MR angiography. The aim of this study was to investigate the
      potential of a new dedicated renal MRI stent for artifact-free in-stent lumen
      visualization in vitro and in a swine model. METHODS AND RESULTS: In vitro
      investigations were performed with prototypes of balloon-expandable Aachen
      Resonance Renal MRI Stents dilated to diameters of 3 to 6 mm and placed in an
      aqueous gadolinium solution (1:25). Phase-contrast and contrast-enhanced T1
      weighted gradient echo images were acquired. Renal MRI stents (n=12) were
      deployed in the renal arteries of 6 pigs. Renal arteries were examined with phase
      contrast angiography and with flow measurements before and after stent placement
      in the stented area, respectively. Additionally, a contrast-enhanced, T1
      weighted, spoiled-gradient echo sequence after administration of 0.2 mmol
      gadolinium-DTPA/kg body weight was performed after stent placement. The
      visibility of artifacts was analyzed on in vitro and in vivo images by two
      investigators who knew the stent positions. Stent positions were determined
      visually (in vitro) or by x-ray angiography (animal experiments). No artifacts
      were detected independent of the applied imaging sequence and the stent
      orientation to the main magnetic field. CONCLUSION: The examined prototypes of
      fully MR-compatible MRI stents allow artifact-free visualization of the stent
      lumen with phase-contrast and contrast-enhanced T1-weighted angiography, as well
      as phase-contrast flow measurements in the stented area.

PMID- 11956118
TI  - Plasma homocysteine concentration, statin therapy, and the risk of first acute
      coronary events.
AB  - BACKGROUND: Elevated homocysteine levels are associated with increased coronary
      risk, and it has been suggested that homocysteine screening may provide a method
      to identify high-risk patients for aggressive primary prevention. METHODS AND
      RESULTS: Homocysteine was measured at baseline and after 1 year among 5569
      participants in the Air Force/Texas Coronary Atherosclerosis Prevention Study
      (AFCAPS/TexCAPS), a randomized trial of lovastatin in the primary prevention of
      acute coronary events. The effects of homocysteine, LDL cholesterol, and
      lovastatin on risk were assessed over 5.2 years of trial follow-up. Median
      baseline homocysteine levels were significantly higher among study participants
      who subsequently had acute coronary events compared with those who did not (12.1
      versus 10.9 micro;mol/L, P<0.001). The relative risks of future events from
      lowest (referent) to highest quartile of homocysteine were 1.0, 1.6, 1.6, and 2.2
      (P<0.001). These effects were similar among those allocated to lovastatin and
      those allocated to placebo and were modestly attenuated after adjustment for
      other traditional risk factors. As predicted, the subgroup of participants with
      elevated LDL cholesterol and elevated homocysteine levels were at high risk and
      benefited greatly from statin therapy (relative risk, 0.46; 95% CI, 0.29 to 0.75;
      number needed to treat=26). However, in contrast to findings in this trial for C
      reactive protein, homocysteine evaluation did not help to define low LDL
      subgroups with different responses to lovastatin therapy. CONCLUSIONS: Although
      homocysteine predicted future coronary events in AFCAPS/TexCAPS, we found little
      evidence that homocysteine evaluation provided an improved method to target
      statin therapy among those with low-to-normal LDL cholesterol levels.

PMID- 11956119
TI  - Mental stress-induced ischemia and all-cause mortality in patients with coronary
      artery disease: Results from the Psychophysiological Investigations of Myocardial
      Ischemia study.
AB  - BACKGROUND: Ischemia during laboratory mental stress tests has been linked to
      significantly higher rates of adverse cardiac events. Previous studies have not
      been designed to detect differences in mortality rates. METHODS AND RESULTS: To
      determine whether mental stress-induced ischemia predicts death, we evaluated 196
      patients from the Psychophysiological Investigations of Myocardial Ischemia
      (PIMI) study who had documented coronary artery disease and exercise-induced
      ischemia. Participants underwent bicycle exercise and psychological stress
      testing with radionuclide imaging. Cardiac function data and psychological test
      results were collected. Vital status was ascertained by telephone and by querying
      Social Security records 3.5+/-0.4 years and 5.2+/-0.4 years later. Of the 17
      participants who had died, new or worsened wall motion abnormalities during the
      speech test were present in 40% compared with 19% of survivors (P=0.04) and
      significantly predicted death (rate ratio=3.0; 95% CI, 1.04 to 8.36; P=0.04).
      Ejection fraction changes during the speech test were similar in patients who
      died and in survivors (P=0.9) and did not predict death even after adjusting for
      resting ejection fraction (P=0.63), which was similar in both groups (mean, 56.4
      versus 59.7; P=0.24). Other indicators of ischemia during the speech test (ST
      segment depression, chest pain) did not predict death, nor did psychological
      traits, hemodynamic responses to the speech test, or markers of the presence and
      severity of ischemia during daily life and exercise. CONCLUSIONS: In patients
      with coronary artery disease and exercise-induced ischemia, the presence of
      mental stress-induced ischemia predicts subsequent death.

PMID- 11956120
TI  - Physical activity and hemostatic and inflammatory variables in elderly men.
AB  - BACKGROUND: Physical activity is associated with lower risk of cardiovascular
      disease, but the mechanisms are uncertain. Hemostatic and inflammatory markers
      have been linked with risk of cardiovascular disease. We therefore examined the
      relationship between physical activity and hemostatic and inflammatory variables.
      METHODS AND RESULTS: In 1998 to 2000, 20 years after the initial screening of
      7735 men 40 to 59 years old from general practices in 24 British towns, 4252
      subjects (77% of available survivors, now 60 to 79 old) attended for
      reexamination. A fasting blood sample was available in 4088 men. All men on
      warfarin (n=134) and men with incomplete data on physical activity (n=144) were
      excluded, leaving 3810 men for analysis. Physical activity showed a significant
      and inverse dose-response relationship with fibrinogen, plasma and blood
      viscosity, platelet count, coagulation factors VIII and IX, von Willebrand
      factor, fibrin D-dimer, tissue plasminogen activator antigen, C-reactive protein,
      and white cell count, even after adjustment for possible confounders. The effects
      were similar in men with and without prevalent cardiovascular disease. No
      relationship was seen with activated partial thromboplastin time, activated
      protein C resistance, hematocrit, or factor VII. An examination of changes in
      physical activity between baseline and 20 years later showed that inactive men
      who took up at least light physical activity had levels of blood variables
      approaching those who remained at least lightly active. Those who became inactive
      showed levels more similar to those who remained inactive. CONCLUSIONS: These
      data suggest that the benefit of physical activity on cardiovascular disease may
      be at least partly a result of effects on hemostasis and inflammation.

PMID- 11956121
TI  - Continuous probabilistic prediction of angiographically significant coronary
      artery disease using electron beam tomography.
AB  - BACKGROUND: We sought to incorporate electron beam tomography-derived calcium
      scores in a model for prediction of angiographically significant coronary artery
      disease (CAD). Such a model could greatly facilitate clinical triage in
      symptomatic patients with no known CAD. METHODS AND RESULTS: We examined 1851
      patients with suspected CAD who underwent coronary angiography for clinical
      indications. An electron beam tomographic scan was performed in all patients.
      Total per-patient calcium scores and separate scores for the major coronary
      arteries were added to logistic regression models to calculate a posterior
      probability of the severity and extent of angiographic disease. These models were
      designed to be continuous, adjusted for age and sex, corrected for verification
      bias, and independently validated in terms of their incremental diagnostic
      accuracy. The overall sensitivity was 95%, and specificity was 66% for coronary
      calcium to predict obstructive disease on angiography. With calcium scores >20,
      >80, and >100, the sensitivity to predict stenosis decreased to 90%, 79%, and
      76%, whereas the specificity increased to 58%, 72%, and 75%, respectively. The
      logistic regression model exhibited excellent discrimination (receiver operating
      characteristic curve area, 0.842+/-0.023) and calibration (chi2 goodness of fit,
      8.95; P=0.442). CONCLUSIONS: Electron beam tomographic calcium scanning provides
      incremental and independent power in predicting the severity and extent of
      angiographically significant CAD in symptomatic patients, in conjunction with
      pretest probability of disease. This algorithm is most useful when applied to an
      intermediate-risk population.

PMID- 11956123
TI  - Biological gradient between long-term arsenic exposure and carotid
      atherosclerosis.
AB  - BACKGROUND: Long-term exposure to ingested arsenic has been documented to induce
      peripheral vascular disease, ischemic heart disease, and cerebral infarction in a
      dose-response relationship. This study further examined the biological gradient
      between ingested inorganic arsenic and carotid atherosclerosis. METHODS AND
      RESULTS: We studied 199 male and 264 female adult residents from the southwestern
      area of endemic arseniasis in Taiwan. The extent of carotid atherosclerosis was
      assessed by duplex ultrasonography. Diabetes mellitus was determined by oral
      glucose tolerance test, hypertension by mercury sphygmomanometers, and serum
      lipid profiles by autoanalyzers. Information regarding the consumption of high
      arsenic artesian well water, cigarette smoking, and alcohol consumption was
      obtained through standardized questionnaire interviews. Logistic regression
      analysis was used to estimate the odds ratio and its 95% CI of carotid
      atherosclerosis for various risk factors. Three indices of long-term exposure to
      ingested arsenic, including the duration of consuming artesian well water, the
      average arsenic concentration in consumed artesian well water, and cumulative
      arsenic exposure, were all significantly associated with prevalence of carotid
      atherosclerosis in a dose-response relationship. The biological gradient remained
      significant after adjustment for age, sex, hypertension, diabetes mellitus,
      cigarette smoking, alcohol consumption, waist-to-hip ratio, and serum levels of
      total cholesterol and LDL cholesterol. The multivariate-adjusted odds ratio was
      3.1 (95% CI 1.3 to 7.4) for those who had a cumulative arsenic exposure of > or
      =20 mg/L-years compared with those without exposure to arsenic from drinking
      artesian well water. CONCLUSIONS: Carotid atherosclerosis is associated with
      ingested inorganic arsenic, showing a significant biological gradient.

PMID- 11956122
TI  - Effects of sustained-release moxonidine, an imidazoline agonist, on plasma
      norepinephrine in patients with chronic heart failure.
AB  - BACKGROUND: In chronic heart failure, sympathetic activation is increased.
      Moxonidine acts on central nervous system receptors to decrease sympathetic
      activation. We investigated the dose-response relationship of a new sustained
      release (SR) preparation of moxonidine and the plasma concentration of
      norepinephrine in patients with chronic heart failure. METHODS AND RESULTS: A
      total of 268 patients with chronic heart failure in NYHA functional class II to
      IV on optimal standard therapy were randomized to placebo or 1 of 5 doses of
      moxonidine SR: 0.3, 0.6, 0.9, 1.2, or 1.5 mg BID. After a dose-titration phase (7
      weeks), patients were followed up for another 12 weeks at their maximally
      tolerated dose. Blood samples for plasma norepinephrine were collected at
      baseline and weekly during the initial 7 weeks, at week 19, and at the end of the
      study. At baseline and 7 and 19 weeks, sampling was also done 4 hours after the
      dose. After the active phases of the study, plasma norepinephrine was evaluated
      for an additional 3 days. A marked, statistically significant dose-related
      decrease in plasma norepinephrine was observed for predose levels as well as 4
      hours after the dose at week 19. At the highest dose (1.5 mg BID), the trough
      reduction in norepinephrine was 52%. These reductions were accompanied by a
      modest decrease in heart rate, a modest increase in left ventricular ejection
      fraction, and a dose-related increase in adverse events. CONCLUSIONS: Plasma
      norepinephrine was markedly reduced in a dose-related manner by moxonidine SR.
      This reduction was accompanied by evidence of reverse remodeling, but also by an
      increase in adverse events.

PMID- 11956124
TI  - Does oral folic acid lower total homocysteine levels and improve endothelial
      function in children with chronic renal failure?
AB  - BACKGROUND: Accelerated vascular disease is common in chronic renal failure (CRF)
      and accounts for significant mortality and morbidity. Elevated homocysteine
      levels may contribute by an effect on endothelial function. METHODS AND RESULTS:
      We performed a double-blind placebo-controlled randomized crossover trial of
      folic acid at 5 mg/m2 in 25 normotensive children 12+/-3 (7 to 17) years of age
      with CRF (glomerular filtration rate 26.8+/-13.2 mL/min per 1.73 m2) of
      noninflammatory etiology. Each subject underwent two 8-week periods of folic acid
      and placebo separated by an 8-week washout period. The effect of folic acid on
      homocysteine levels, LDL oxidation, and both endothelial-dependent and 
      independent vascular function were measured. After oral folic acid, serum folate
      levels rose from 11.7+/-4.25 to 635+/-519 microg/L (P=0.001), red cell folate
      levels rose from 364+/-195 to 2891+/-2623 microg/L (P<0.001), and total
      homocysteine levels fell from 10.28+/-4.16 to 8.62+/-2.32 micromol/L (P=0.03). In
      addition, there was a significant improvement in flow-mediated dilatation (FMD)
      (endothelial-dependent dilatation) from 7.21+/-2.8% to 8.47+/-3.01% (P=0.036)
      with no change in response to glyceryl trinitrate (endothelial-independent
      dilatation). There was no significant change in FMD or glyceryl trinitrate during
      the placebo phase. There was, however, no significant difference in final FMD
      after placebo or folic acid. Lag times for LDL oxidation were prolonged during
      the treatment phase (58.4+/-18.7 to 68.1+/-25.9 minutes, P=0.01). CONCLUSION:
      Folic acid supplementation in children with CRF may improve endothelial function
      with an increased resistance of LDL to oxidation.

PMID- 11956126
TI  - Genetic modifier loci affecting survival and cardiac function in murine dilated
      cardiomyopathy.
AB  - BACKGROUND: Understanding the role for genetic factors in human heart failure is
      difficult because environmental factors cannot be standardized and genetic
      variation is great. One approach to identify genes that modify disease outcome is
      to use mouse models that show strong genetic variation of the disease phenotype.
      METHODS AND RESULTS: In this study, we used transgenic mice that develop severe
      dilated cardiomyopathy due to the cardiac-specific overexpression of
      calsequestrin. Transgenic mice showed marked strain-specific variation of cardiac
      function and survival, independent of transgene expression. A reciprocal
      backcross strategy was employed using two inbred strains showing distinct
      differences in survival and cardiac function. To map the genes that modified the
      heart failure phenotype, progeny from the 2 reciprocal backcrosses were used in a
      genome-wide scan for linkage. We identified two loci significantly linked to
      survival with a maximum likelihood ratio statistic of 36.2 (LOD score
      approximately 7.8) on chromosome 2 and of 26.5 (LOD score approximately 5.7) on
      chromosome 3. The chromosome 3 locus was also significantly linked to cardiac
      function with a maximum likelihood ratio statistic of 42.9 (LOD score
      approximately 9.3). Because only a single strong modifier locus was found in each
      backcross, we applied a haplotype analysis to map crossovers and successfully
      narrowed the critical intervals for each locus. CONCLUSION: Using a sensitized
      mouse model, we identified major modifier loci that affect the genetically
      complex disease of heart failure. This approach should allow the rapid
      identification of candidate genes involved in disease susceptibility in human
      populations and new insights into the pathogenesis of heart failure.

PMID- 11956125
TI  - Cyclooxygenase-2 promotes early atherosclerotic lesion formation in LDL receptor
      deficient mice.
AB  - BACKGROUND: Atherosclerosis has features of an inflammatory disease. Because
      cyclooxygenase (COX)-2 is expressed in atherosclerotic lesions and promotes
      inflammation, we tested the hypotheses that selective COX-2 inhibition would
      reduce early lesion formation in LDL receptor-deficient (LDLR-/-) mice and that
      macrophage COX-2 expression contributes to atherogenesis in LDLR-/- mice. METHODS
      AND RESULTS: Treatment of male LDLR-/- mice fed the Western diet with rofecoxib
      or indomethacin for 6 weeks resulted in significant reductions in atherosclerosis
      in the proximal aorta (25% and 37%) and in the aorta en face (58% and 57%),
      respectively. Rofecoxib treatment did not inhibit platelet thromboxane
      production, a COX-1-mediated process, but it significantly reduced the urinary
      prostacyclin metabolite 2,3-dinor-6-keto-PGF1alpha. Fetal liver cell
      transplantation was used to generate LDLR-/- mice null for expression of the COX
      2 gene by macrophages. After 8 weeks on the Western diet, COX-2-/- --> LDLR-/-
      mice developed significantly less (33% to 39%) atherosclerosis than control COX
      2+/+ --> LDLR-/- mice. In both the inhibitor studies and the transplant studies,
      serum lipids did not differ significantly between groups. CONCLUSIONS: The
      present studies provide strong pharmacological and genetic evidence that COX-2
      promotes early atherosclerotic lesion formation in LDLR-/- mice in vivo. These
      results support the potential of anti-inflammatory approaches to the prevention
      of atherosclerosis.

PMID- 11956127
TI  - Enhanced expression of the LDL receptor family member LR11 increases migration of
      smooth muscle cells in vitro.
AB  - BACKGROUND: LR11, a member of the LDL receptor family, is highly expressed in
      vascular smooth muscle cells (SMCs) of the hyperplastic intima but not media. To
      further clarify the involvement of LR11 in the process of atherosclerosis, we
      have characterized the migration and invasion activities of LR11-overexpressing
      SMCs. METHODS AND RESULTS: LR11 cDNA was transfected into the rat SMC line A7r5.
      Compared with mock cells (C-1), in the presence of platelet-derived growth factor
      BB, the transfected cells (R-1 and R-2) showed 3.5- to 4.0-fold higher expression
      of LR11 protein, 1.7- to 1.8-fold increased migration, and 2.0- to 2.2-fold
      elevated invasion activities, respectively. The increases were essentially
      abolished by the addition of receptor-associated protein, anti-LR11 antibodies,
      or apolipoprotein E. Immunological analyses showed that urokinase-type
      plasminogen activator receptor (uPAR) levels were increased in LR11
      overexpressing cells. Anti-urokinase-type plasminogen activator (uPA) and anti
      uPAR antibodies reduced the migration and invasion activities of R-1 and R-2
      cells to baseline levels. Receptor-associated protein, anti-LR11 antibodies, and
      apolipoprotein E decreased uPAR expression in the LR11-overexpressing cells by
      approximately 50%. Cellular catabolism of uPAR was significantly decreased in R-1
      and R-2 cells compared with control. Cultured SMCs isolated from intima of
      atherosclerotic rabbit aortas showed increased expression levels of LR11 and uPAR
      and enhanced migration and invasion compared with SMCs from medial layers.
      CONCLUSIONS: Overexpression of LR11 induces enhanced migration and invasion
      activities of intimal SMCs in vitro, probably through its regulation of the
      uPA/uPAR system.

PMID- 11956128
TI  - Myocardial fibrosis in chronic aortic regurgitation: molecular and cellular
      responses to volume overload.
AB  - BACKGROUND: Myocardial fibrosis is common in patients with chronic aortic
      regurgitation (AR). Experimentally, fibrosis with disproportionate noncollagen
      extracellular matrix (ECM) elements precedes and contributes to heart failure in
      AR. METHODS AND RESULTS: We assessed [3H]-glucosamine and [3H]-proline
      incorporation in ECM, variations in cardiac fibroblast (CF) gene expression, and
      synthesis of specific ECM proteins in CF cultured from rabbits with surgically
      induced chronic AR versus controls. To determine whether these variations are
      primary responses to AR, normal CF were exposed to mechanical strain that
      mimicked that of AR. Compared with normal CF, AR CF incorporated more glucosamine
      (1.8:1, P=0.001) into ECM, showed fibronectin gene upregulation (2.0:1, P=0.02),
      and synthesized more fibronectin (2:1 by Western blot, P<0.06; 1.5:1 by affinity
      chromatography, P=0.02). Proline incorporation was unchanged by AR (1.1:1, NS);
      collagen synthesis was unaffected (type I, 0.9:1; type III, 1.0:1, NS). Normal CF
      exposed to cyclical mechanical strain during culture showed parallel results:
      glucosamine incorporation increased with strain (2.1:1, P<0.001), proline
      incorporation was unaffected (1.1:1, NS), fibronectin gene expression (1.6:1,
      P=0.07) and fibronectin synthesis (Western analysis, 1.3:1, P<0.01;
      chromatography, 1.9:1, NS) were upregulated. CONCLUSIONS: In AR, CF produce
      abnormal proportions of noncollagen ECM, specifically fibronectin, with
      relatively little change in collagen synthesis. At least in part, this is a
      primary response to strain imposed on CF by AR. Further study must relate these
      findings to the pathogenesis of heart failure in AR.

PMID- 11956129
TI  - Use of a blood substitute to determine instantaneous murine right ventricular
      thickening with optical coherence tomography.
AB  - BACKGROUND: A satisfactory imaging technique to determine regional wall
      thickening of the murine myocardium is not available. Although cardiovascular
      imaging with light offers a novel solution, application is problematic because
      scattering by erythrocytes causes significant optical attenuation. METHODS AND
      RESULTS: Optical coherence tomography (OCT) is a technique for detailed
      resolution imaging of highly scattering biological tissues. To reduce the high
      level of blood scattering, a method was devised whereby murine blood was replaced
      with a hemoglobin-based blood substitute. The scattering and absorption
      properties of in vitro preparations of whole blood and dilutions of blood with a
      blood substitute were determined with a spectrophotometer and an inverse-adding
      doubling algorithm. OCT imaging of the same dilutions demonstrated a significant
      reduction in scattering at a hematocrit <5%. A fiber-optic OCT imaging system was
      used to image the murine right midventricular free wall before and after
      isovolumic replacement with blood substitute. Strong light attenuation prevented
      full thickness imaging before replacement, whereas visualization of the full
      ventricular thickness was possible after replacement. Baseline and imaging
      hematocrits were 52.4+/-3.8% and 3.7+/-1.2%, respectively. End-systolic and end
      diastolic thickness values were 0.458+/-0.051 mm and 0.352+/-0.047 mm. Percent
      thickening fraction was 30.8+/- 7.5%. CONCLUSION: Optical imaging of the intact
      beating murine right ventricle was substantially improved by isovolumic blood
      replacement with a hemoglobin-based blood substitute. Although the current study
      has been directed toward imaging the murine heart, a blood substitute may be
      applied to various optical diagnostic and therapeutic techniques under
      investigation in cardiovascular medicine.

PMID- 11956130
TI  - Inhibition of calcineurin and sarcolemmal Ca2+ influx protects cardiac morphology
      and ventricular function in K(v)4.2N transgenic mice.
AB  - BACKGROUND: Cardiac-targeted expression of truncated K(v)4.2 subunit (K(v)4.2N)
      reduces transient outward current (I(to)) density, prolongs action potentials
      (APs), and enhances contractility in 3- to 4-week-old transgenic mice. By 13 to
      15 weeks of age, these mice develop severely impaired cardiac function and signs
      of heart failure. In this study, we examined whether augmented contractility in
      K(v)4.2N mice results from elevations in intracellular calcium ([Ca2+]i)
      secondary to AP prolongation and investigated the putative roles of calcineurin
      activation in heart disease development of K(v)4.2N mice. METHODS AND RESULTS: At
      3 to 4 weeks of age, L-type Ca2+ influx and peak [Ca2+]i were significantly
      elevated in K(v)4.2N myocytes compared with control because of AP prolongation.
      Cardiac calcineurin activity was also significantly elevated in K(v)4.2N mice by
      5 weeks of age relative to controls and increased progressively as heart disease
      developed. This was associated with activation of protein kinase C (PKC)-alpha
      and PKC-theta but not PKC-epsilon, as well as increases in beta-myosin heavy
      chain (beta-MHC) and reductions in sarcoplasmic/endoplasmic reticulum Ca2+-ATPase
      (SERCA)-2a expression. Treatment with either cyclosporin A or verapamil prevented
      increases in heart weight to body weight ratios, interstitial fibrosis, impaired
      contractility, PKC activation, and changes in the expression patterns of beta-MHC
      and SERCA2a. CONCLUSIONS: Our results demonstrate that AP prolongation caused by
      I(to) reduction results in enhanced Ca2+ cycling and hypercontractility in mice
      and suggests that elevations in [Ca2+]i via I(Ca,L) and activation of calcineurin
      play a central role in disease development after I(to) reduction using the
      K(v)4.2N construct.

PMID- 11956131
TI  - The chain of scientific discovery: the critical role of the physician-scientist.

PMID- 11956132
TI  - Adaptation and maladaptation of the heart in diabetes: Part II: potential
      mechanisms.

PMID- 11956133
TI  - Images in cardiovascular medicine. Fulminant Clostridium septicum aortitis.

PMID- 11956134
TI  - Images in cardiovascular medicine. Fibrillary/immunotactoid glomerulopathy with
      cardiac involvement.

PMID- 11956136
TI  - Minireview: Neuro-immuno-endocrine modulation of the hypothalamic-pituitary
      adrenal (HPA) axis by gp130 signaling molecules.
AB  - The neuroendocrine and immune systems communicate bidirectionally. The neuro
      immune-endocrine interface is mediated by cytokines acting as auto/paracrine or
      endocrine factors regulating pituitary development, cell proliferation, hormone
      secretion, and feedback control of the hypothalamic-pituitary-adrenal (HPA) axis.
      At birth or during neonatal ontogenesis, cytokines produce permanent alterations
      of HPA axis function and the stress response. Overexpressing IL-6 or leukemia
      inhibitory factor leads to significant changes in pituitary development and
      functions. Pituitary corticotroph POMC gene expression is regulated by CRH as
      well as several gp130 cytokines acting as neuro-immuno-endocrine modulators.
      Conversely, HPA axis functions modulate susceptibility or resistance to
      inflammatory disease. Cytokines (including IL-1, TNF, and members of the gp130
      cytokine family) participate as mediators of a complex HPA axis response to
      stress and inflammation. Prolonged exposure to proinflammatory cytokines
      increases levels of the dominant negative glucocorticoid receptor isoform.
      Nonresponsiveness of the HPA axis to glucocorticoid negative feedback control
      provides a defense from destructive effects of cytokine excess. At the same time,
      gp130 cytokines stimulate pituitary suppressor of cytokine signaling (SOCS)-3,
      which represses cytokine signaling and abrogates cytokine-induced corticotroph
      POMC gene transcription and ACTH secretion.

PMID- 11956137
TI  - Editorial: Never enough--on the multiplicity and uniqueness of transcriptional
      regulators in postmeiotic male germ cells.

PMID- 11956138
TI  - Atce1: a novel mouse cyclic adenosine 3',5'-monophosphate-responsive element
      binding protein-like gene exclusively expressed in postmeiotic spermatids.
AB  - Members of the ATF/CREB family of transcription factors are involved in gene
      activation in various physiological systems ranging from metabolite homeostasis,
      through regulation of cell cycle, to learning and memory. Two members of this
      family, cAMP-responsive element binding protein (CREB), and cAMP-responsive
      element modulator (CREM) are active during mammalian spermatogenesis and are
      required for this process, as has been shown by knockout and dominant negative
      experiments. In an effort to identify mouse proteins that interact with the
      testis-specific protein Tctex2, a mouse testis expression library was screened
      via the two-hybrid system, using the carboxyl-terminal portion of this protein as
      bait. A clone containing two overlapping open reading frames, related by a
      frameshift of one nucleotide, was subsequently isolated. The peptide that
      interacted with Tctex2 does not initiate from a consensus AUG codon, and it is
      not clear whether it exists physiologically. However, the other reading frame,
      initiating from an AUG codon, encodes a 315-amino acid peptide with significant
      sequence homology to a subfamily of the CREB genes whose prototype is the mouse
      LZIP peptide. This novel CREB-like peptide, designated Atce1, is specifically
      expressed in the testis. A developmental study using Northern hybridization and
      in situ hybridization analyses revealed that Atce1 transcripts begin to
      accumulate in testes of mice 24 d after birth, reflecting expression in mid/late
      round spermatids. Interestingly, EMSAs revealed that in vitro translated Atce1
      binds specifically to a nuclear factor-kappaB-binding element rather then to a
      CRE element. Potential roles for Atce1 are discussed.

PMID- 11956139
TI  - Role of ghrelin in the regulation of vasopressin release in conscious rats.
AB  - GH secretagogue (GHS) is a small, synthetic compound that has the potential to
      stimulate GH release via its specific receptors (GHS-R). Ghrelin is a novel 28
      amino acid peptide recently isolated from human and rat stomach, and it is
      thought to be the endogenous ligand for GHS-R. Ghrelin has a variety of
      physiological functions such as the stimulation of GH release or the increase of
      food intake by activating NPY neurons. In the present study, we investigated the
      effects of ghrelin on AVP release in conscious rats. Intracerebroventricular
      (icv) administration of ghrelin increased the plasma AVP concentration in a dose
      dependent manner (1-1000 pmol/rat), and its effect was observed as late as 60 min
      after the administration. Icv injection of ghrelin caused no significant change
      in plasma osmolality, plasma volume, or arterial blood pressure. Iv
      administration of ghrelin (10 nmol/rat) also increased the plasma AVP
      concentration, which was accompanied by a significant decrease in arterial blood
      pressure. Pretreatment with antiserum against NPY significantly reduced the
      plasma AVP increase induced by icv administration of ghrelin. These results
      suggest that ghrelin plays a stimulatory role in AVP release, which is possibly
      mediated by NPY neurons.

PMID- 11956140
TI  - Osteoblastic response to the defective matrix in the osteogenesis imperfecta
      murine (oim) mouse.
AB  - This work examines the cellular pathophysiology associated with the weakened bone
      matrix found in a murine model of osteogenesis imperfecta murine (oim).
      Histomorphometric analysis of oim/oim bone showed significantly diminished bone
      mass, and the osteoblast and osteoclast histomorphometric parameters were
      increased in the oim/oim mice, compared with wild-type (+/+) mice. To assess
      osteoblast activity, a rat Col1a1 promoter linked to the chloramphenicol
      acetyltransferase reporter transgene was bred into the oim model. At 8 d and 1
      month of age, no difference in transgene activity between oim and control mice
      was observed. However, at 3 months of age, chloramphenicol acetyl transferase
      activity was elevated in oim/oim;Tg/Tg, compared with +/+;Tg/Tg and oim/+;Tg/Tg.
      High levels of urinary pyridinoline crosslinks in the oim/oim;Tg/Tg mice were
      present at all ages, reflecting continuing high bone resorption. Our data portray
      a state of ineffective osteogenesis in which the mutant mouse never accumulates a
      normal quantity of bone matrix. However, it is only after the completion of the
      rapid growth phase that the high activity of the oim/oim osteoblast can
      compensate for the high rate of bone resorption. This relationship between bone
      formation and resorption may explain why the severity of osteogenesis imperfecta
      decreases after puberty is completed. The ability to quantify high bone turnover
      and advantages of using a transgene that reflects osteoblast lineage activity
      make this a useful model for studying interventions designed to improve the bone
      strength in osteogenesis imperfecta.

PMID- 11956141
TI  - Guinea pig GnRH: localization and physiological activity reveal that it, not
      mammalian GnRH, is the major neuroendocrine form in guinea pigs.
AB  - The isolation of GnRH cDNA from guinea pig hypothalamus predicted a novel form of
      GnRH with two unique amino acid substitutions relative to all known forms of this
      essential decapeptide. The predicted substitution at amino acid 2 in guinea pig
      (gp) GnRH was particularly intriguing because of the proposed importance of
      position 2 for binding and activation of the GnRH receptor. In the present study,
      gpGnRH was synthesized, and a specific antibody was generated and used to assess
      translation of the gpGnRH transcript. The localization of intensely labeled
      gpGnRH-positive cell bodies and processes in tissue sections through the preoptic
      area and hypothalamus argue that gpGnRH is the major neuroendocrine form of GnRH
      in guinea pigs. Guinea pig GnRH stimulated LH release in guinea pigs and
      increased LH output from guinea pig pituitary fragments, thus demonstrating
      biological activity in this species. In contrast, gpGnRH demonstrated little
      ability to stimulate LH release in rats, a species known to possess the highly
      conserved mammalian GnRH receptor. These findings suggest that: (1) the amino
      acid substitutions in gpGnRH impede binding to and/or activation of the mammalian
      GnRH receptor, and (2) the unique amino acid substitutions in gpGnRH are
      accompanied by changes in the guinea pig GnRH receptor.

PMID- 11956142
TI  - Follistatin-related protein and follistatin differentially neutralize endogenous
      vs. exogenous activin.
AB  - Follistatin-related protein (FSRP) is a new addition to the expanding follistatin
      (FS)-related gene family whose members contain at least one conserved 10-cysteine
      follistatin domain. In contrast to other members of this family, FSRP and
      follistatin also share a common exon/intron domain structure, substantial primary
      sequence homology, and an ability to irreversibly bind activin. In this study, we
      further explored the hypothesis that FSRP is a functional as well as structural
      homologue of FS. N-terminal sequencing of recombinant FSRP revealed that signal
      peptide cleavage occurs within exon 1, a significant structural difference from
      FS, in which cleavage occurs at the exon/intron boundary. Solid-phase radioligand
      competition assays revealed both FS and FSRP to preferentially bind activin with
      the next closest TGF-beta superfamily member, bone-morphogenic protein-7, being
      at least 500-fold less potent. Consistent with their similar activin-binding
      affinities, FSRP and FS both prevented exogenous (endocrine or paracrine) activin
      from accessing its receptor and inducing gene transcription in bioassays.
      However, FS was at least 100-fold more potent than FSRP in inhibiting gene
      transcription and FSH release mediated by endogenously produced (autocrine)
      activin-A or activin-B in multiple cell systems. Finally, FSRP lacks the heparin
      binding sequence found in FS, and we found that it was also unable to bind cell
      surface heparin sulfated proteoglycans. These findings suggest that structural
      differences between FSRP and FS may underlie their different neutralizating
      capabilities with respect to exogenous vs. endogenous activin. Taken together
      with our previous studies showing that activin binding is essential for FS's
      biological activity, the differential activities of FSRP and FS further indicate
      that activin binding is necessary but not sufficient to account for all of FS's
      actions.

PMID- 11956143
TI  - Cellular and molecular events associated with the bone-protecting activity of the
      noncalcemic vitamin D analog Ro-26-9228 in osteopenic rats.
AB  - We have examined several analogs of 1alpha,25-dihydroxyvitamin D(3) [1,25
      (OH)(2)D(3)] in an animal model of osteoporosis (ovariectomized rats) to identify
      a compound with a greater therapeutic range than 1,25-(OH)(2)D(3) for treatment
      of this bone disease. Here, we report that one analog, Ro-26-9228, had a bone
      protecting effect but did not induce hypercalcemia at a wide concentration range.
      Analysis of biochemical markers and the bone histomorphometry of analog-treated
      rats suggested that Ro-26-9228 acted by inhibiting bone resorption and increasing
      the number of differentiated osteoblasts. To determine the basis for the
      segregation between hypercalcemia and bone-protecting action, we examined gene
      expression in tissues that regulate calcium homeostasis. We found that 1,25
      (OH)(2)D(3) induced 24-hydroxylase mRNA expression in the duodena of
      ovariectomized rats, but Ro-26-9228 did not. Furthermore, in the duodena of
      intact animals, 1,25-(OH)(2)D(3) induced a significant increase in calbindin D 9K
      and plasma membrane calcium pump 1 mRNAs, but Ro-26-9228 had no effect on these
      mRNAs. On the other hand, the osteoblast-specific gene products osteocalcin and
      osteopontin were significantly up-regulated in trabecular bone by both the
      natural hormone and Ro-26-9228. Further investigation of gene-regulatory events
      in trabecular bone revealed that both 1,25-(OH)(2)D(3) and Ro-26-9228 up
      regulated TGF beta1 and beta2 mRNAs. We concluded that the unique properties of
      Ro-26-9228 include preferential gene regulation in osteoblasts over duodenum and
      effective induction of growth factors in bone.

PMID- 11956144
TI  - Age-related decreases in Leydig cell testosterone production are not restored by
      exposure to LH in vitro.
AB  - Aging in Brown Norway rats is associated with reduced Leydig cell T production.
      To address the mechanism by which aging Leydig cells become steroidogenically
      hypofunctional, Leydig cells from young and old rat testes were isolated and
      cultured long-term with LH. Leydig cells isolated from young rats that had
      received LH-suppressive T implants served as positive controls. The ability of
      young control Leydig cells to produce T at high levels was sustained over a 3-d
      culture period. T production by cells from young LH-suppressed rats increased
      over this period, almost to control levels. In contrast, culture of the
      steroidogenically hypofunctional old Leydig cells with LH failed to increase
      their T production, suggesting that LH stimulation, by itself, is unable to
      reverse the steroidogenic deficits of old Leydig cells. Reduced numbers of LH
      binding sites characterized Leydig cells from old rats and LH-suppressed young
      rats. However, whereas Leydig cells from young LH-suppressed rats produced cAMP
      at the high levels of young control cells, the old cells produced far less cAMP,
      suggesting that old Leydig cells have defects in the LH-cAMP signaling cascade.
      When stimulated with forskolin, old cells produced the same amount of cAMP as
      young control and young LH-suppressed cells, suggesting that adenylate cyclase is
      maintained in the old cells. Taken together, these results suggest that
      inefficient signal transduction may explain the reduced steroidogenesis that
      characterizes old Leydig cells.

PMID- 11956145
TI  - Estrogen-binding sites and their functional capacity in estrogen receptor double
      knockout mouse brain.
AB  - Early studies found estrogen-binding sites in the ER knockout (ERalphaKO) mouse
      brain, suggesting a splice variant of ERalpha or another ER. The discovery of
      ERbeta suggested that binding was due to ERbeta, although questions about an
      ERgamma remained. To test this hypothesis, ERbetaKO mice were generated and
      crossed with ERalphaKO mice, and ERalpha/betaKO animals were used for in vivo
      binding studies with [(125)I]estrogen. The results revealed nuclear binding sites
      in the ERalpha/betaKO hypothalamus and amygdala. As the binding resembled the
      distribution of ERalpha, we evaluated the presence of ERalpha splicing variants.
      A nonphysiological splice variant of ERalpha was identified in ERalpha/betaKO
      brain and uterus, but was absent in wild-type mice. ERalpha immunoreactivity was
      also detected in regions of ERalpha/betaKO brain where residual binding was seen.
      To ascertain the functionality of the variant, the regulation of PR was assessed
      in brain. The results revealed that E2 significantly increased PR expression, an
      indication that the variant can regulate gene transcription. These data
      demonstrate the presence and functionality of an ERalpha variant in
      ERalpha/betaKO brain and suggest that the residual binding and regulation of PR
      in ERalpha/betaKO brain can be accounted for by the variant.

PMID- 11956147
TI  - Short-term effects of thyroid hormones and 3,5-diiodothyronine on membrane
      transport systems in chick embryo hepatocytes.
AB  - Rapid nongenomic effects of thyroid hormones L-T(3) and L-T(4) on two plasma
      membrane transport systems were investigated in 14-d-old and 19-d-old chick
      embryo hepatocytes. The Na(+)/H(+) exchanger activity was measured using the
      intracellular pH-sensitive fluorescent probe 2',7'-bis-(2-carboxyethyl)-5-(and-6)
      carboxyfluorescein acetoxymethyl ester, whereas the amino acid transport was
      estimated by [1-(14)C]-2-aminoisobutyric acid uptake. System A amino acid
      transport activation was linear to hormone concentration, whereas the Na/H
      exchanger gave a bell-shaped dose-response curve, with a maximum at the
      physiological hormone concentration of 1 nM. The specificity of the effect was
      verified by the use of inhibitors and analogues. The thyroid hormone analog 3,5
      diiodo-L-thyronine was able to mimic some of the hormone effects, but with a
      lower efficiency. The effect on the Na(+)/H(+) exchanger was identified for 14-d
      old and 19-d-old cells, whereas the amino acid transport could only be activated
      at the late stage of embryo development. Both transport systems were activated
      through a signal transduction pathway involving PKC, MAPK pathway, and PI3K, even
      though the differences in response behavior indicate a differential modulation of
      the two transport systems by L-T(3) and L-T(4). These results clearly demonstrate
      the existence of rapid nongenomic action of thyroid hormones also in avian cells,
      and show that activation of System A amino acid transport is not directly
      correlated to changes in intracellular pH. For the first time, evidence is
      presented which suggests that short-term effects of thyroid hormones may play a
      role during fetal development and cell differentiation.

PMID- 11956146
TI  - Transcriptional activation of the ovine follicle-stimulating hormone-beta gene by
      gonadotropin-releasing hormone involves multiple signal transduction pathways.
AB  - GnRH regulates gonadotrope cells through GnRH receptor activation of the PKC-,
      MAPK-, and calcium-activated signaling cascades. Due to the paucity of homologous
      model systems expressing FSHbeta, little is known about the specific mechanisms
      involved in transcriptional regulation of this gene by GnRH. Previous studies
      from our laboratory demonstrated that the gonadotrope-derived LbetaT2 cell line
      expresses FSHbeta mRNA. In the present study we characterized the mechanisms
      involved in GnRH regulation of the FSHbeta promoter using this cell model. Using
      transfection assays, we show that GnRH regulation of the ovine FSHbeta promoter
      involves at least two elements, present between -4152/-2878 and -2550/-1089 bp,
      in association with one or several elements within the proximal region of the
      promoter. Surprisingly, the two activating protein-1 sites previously shown to be
      involved in the FSHbeta response to GnRH in heterologous cells do not play a role
      in GnRH responsiveness in the gonadotrope cell model. Here we demonstrate that
      calcium influx itself is not sufficient to confer the response, but it is
      necessary for both 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and GnRH induction
      of the FSHbeta gene. Moreover, we show that GnRH regulation of FSHbeta gene
      expression is mediated by PKC and establish the presence of multiple PKC isozymes
      in LbetaT2 cells. Interestingly, GnRH and TPA induce activity of the FSHbeta
      promoter through different, although possibly overlapping, pools of PKC isoforms.
      This is further supported by the use of a MAPK inhibitor, which abolishes the
      induction of FSHbeta by GnRH, but not by TPA. In conclusion, we have demonstrated
      that calcium, PKC, and MAPK signaling systems are all involved in the induction
      of FSHbeta gene expression by GnRH in the LbetaT2 mouse gonadotrope cell model.

PMID- 11956148
TI  - Impaired blockade of insulin-like growth factor I (IGF-I)-induced hypoglycemia by
      IGF binding protein-3 analog with reduced ternary complex-forming ability.
AB  - The hypoglycemic potential of circulating IGFs is thought to be regulated through
      the formation of ternary complexes consisting of an IGF, either IGF binding
      protein-3 (IGFBP-3) or IGFBP-5, and the acid-labile subunit. These high molecular
      weight complexes are confined to the circulation and represent a reservoir of IGF
      with a prolonged half-life. In this study, we show that hypoglycemia, induced by
      a bolus injection of recombinant human IGF-I into rats, can be blocked by
      coadministering equimolar concentrations of either recombinant glycosylated IGFBP
      3 or nonglycosylated IGFBP-3 (IGFBP-3NG). In contrast, an IGFBP-3 mutant with
      reduced acid- labile subunit affinity (IGFBP-3MUT) only partially blocked the IGF
      I hypoglycemic effect. IGFBP-3 and IGFBP-3NG significantly enhanced IGF-I
      retention in the circulation, whereas IGFBP-3MUT had a smaller effect. IGFBP-3MUT
      clearance was more rapid than that of the other IGFBP-3 forms, and the retention
      of all IGFBP-3 forms was greatly enhanced by coadministration of IGF-I.
      Characterization of the molecular mass distribution of the IGFBP-3 analogs
      indicated that 60% of IGFBP-3 and IGFBP-3NG was initially found in ternary
      complexes compared with 30% of IGFBP-3MUT. These data confirm the hypothesis that
      regulation of IGF-I bioactivity in vivo by IGFBP-3 depends on its ability to form
      ternary complexes.

PMID- 11956149
TI  - Binding properties of insulin-like growth factor binding protein-3 (IGFBP-3),
      IGFBP-3 N- and C-terminal fragments, and structurally related proteins mac25 and
      connective tissue growth factor measured using a biosensor.
AB  - We measured the binding of IGF-I and IGF-II to recombinant human N-terminal
      [residues 1-97; recombinant human IGF-binding protein-3(1-97) (rhIGFBP-3(1-97))]
      and C-terminal (residues 98-264; rhIGFBP-3(98-264)) IGFBP-3 fragments and
      compared it with IGF binding to intact IGFBP-3 using biosensor analysis.
      Experiments were carried out in different configurations, either with binding
      protein or fragment immobilized or with IGF immobilized. These experiments showed
      that IGF-I and IGF-II bind to IGFBP-3 with affinities of 4-5 x 10(9) M(-1) and
      similar binding kinetics. The affinities of both rhIGFBP-3(1-97) and rhIGFBP-3(98
      264) for IGF proteins were approximately 3 orders of magnitude less than that of
      full-length IGFBP-3. These results further support the concept that high affinity
      binding of IGF to IGF-binding proteins results from a two-site interaction of IGF
      with both the N- and C-terminal regions of the binding protein. Binding of
      insulin to IGFBP-3 and its N- and C-terminal fragments and of IGF-I and IGF-II to
      the structurally related proteins mac25 and connective tissue growth factor was
      also investigated. Weak insulin binding to full-length IGFBP-3 could be
      demonstrated in a few experiments, but we found that binding of IGF-I, IGF-II,
      and insulin to mac25 or connective tissue growth factor was below the detection
      limit of the biosensor instrument.

PMID- 11956150
TI  - Neuropeptide Y inhibits spontaneous alpha-melanocyte-stimulating hormone (alpha
      MSH) release via a Y(5) receptor and suppresses thyrotropin-releasing hormone
      induced alpha-MSH secretion via a Y(1) receptor in frog melanotrope cells.
AB  - In amphibians, the secretion of alpha-MSH by melanotrope cells is stimulated by
      TRH and inhibited by NPY. We have previously shown that NPY abrogates the
      stimulatory effect of TRH on alpha-MSH secretion. The aim of the present study
      was to characterize the receptor subtypes mediating the action of NPY and to
      investigate the intracellular mechanisms involved in the inhibitory effect of NPY
      on basal and TRH-induced alpha-MSH secretion. Y(1) and Y(5) receptor mRNAs were
      detected by RT-PCR and visualized by in situ hybridization histochemistry in the
      intermediate lobe of the pituitary. Various NPY analogs inhibited in a dose
      dependent manner the spontaneous secretion of alpha-MSH from perifused frog
      neurointermediate lobes with the following order of potency porcine peptide YY
      (pPYY) > frog NPY (fNPY) > porcine NPY (pNPY)-2-36) > pNPY-(13-36) > [D
      Trp(32)]pNPY > [Leu(31),Pro(34)]pNPY. The stimulatory effect of TRH (10(-8)6 M)
      on alpha-MSH release was inhibited by fNPY, pPYY, and [Leu(31),Pro(34)]pNPY, but
      not by pNPY-(13-36) and [D-Trp(32)]pNPY. These data indicate that the inhibitory
      effect of fNPY on spontaneous alpha-MSH release is preferentially mediated
      through Y(5) receptors, whereas the suppression of TRH-induced alpha-MSH
      secretion by fNPY probably involves Y(1) receptors. Pretreatment of
      neurointermediate lobes with pertussis toxin (PTX; 1 microg/ml; 12 h) did not
      abolish the inhibitory effect of fNPY on cAMP formation and spontaneous alpha-MSH
      release, but restored the stimulatory effect of TRH on alpha-MSH secretion,
      indicating that the adenylyl cyclase pathway is not involved in the action of
      fNPY on TRH-evoked alpha-MSH secretion. In the majority of melanotrope cells, TRH
      induces a sustained and biphasic increase in cytosolic Ca(2+) concentration.
      Preincubation of cultured cells with fNPY (10(-7) M) or omega-conotoxin GVIA (10(
      7) M) suppressed the plateau phase of the Ca(2+) response induced by TRH.
      However, although fNPY abrogated TRH-evoked alpha-MSH secretion, omega-conotoxin
      did not, showing dissociation between the cytosolic Ca(2+) concentration increase
      and the secretory response. Collectively, these data indicate that in frog
      melanotrope cells NPY inhibits spontaneous alpha-MSH release and cAMP formation
      through activation of a Y(5) receptor coupled to PTX- insensitive G protein,
      whereas NPY suppresses the stimulatory effect of TRH on alpha-MSH secretion
      through a Y(1) receptor coupled to a PTX-sensitive G protein-coupled receptor.

PMID- 11956151
TI  - Activation of caspase-2 mediates the apoptosis induced by GTP-depletion in
      insulin-secreting (HIT-T15) cells.
AB  - This study investigated the possible involvement of a specific caspase(s) (a
      family of aspartate-specific cysteine proteases) in programmed cell death of
      islet beta-cells due to sustained GTP depletion. Treatment (up to 48 h) with 3
      microg/ml mycophenolic acid (MPA), which specifically depletes intracellular
      guanine nucleotides, reduced cell-cycle progression from G1 phase into S and G2/M
      phases (as assessed by flow cytometry) and, subsequently, induced apoptosis of
      HIT-15 cells (transformed pancreatic beta-cells). The latter was accompanied by a
      marked increase of caspase-2 activity (+343%) and moderate activation of caspase
      9 (+150%) and caspase-3 (+145%). Importantly, only caspase-2 activation preceded
      induction of apoptosis. There was no change in activity of caspase-1, -4, -5, -6,
      and -8. Release of the mitochondrial protein cytochrome c into cytosol was also
      observed at a late stage. Cotreatment of cells with a permeable pan-caspase
      inhibitor (Z-VAD-FMK) blocked GTP depletion-induced cell death in a dose
      dependent manner. A specific caspase-2 inhibitor (Z-VDVAD-FMK), but not a caspase
      3 inhibitor (DEVD-CHO), was also capable of restoring cell viability.
      Interestingly, activation of caspase-2 leads to caspase-3 activation because the
      caspase-2 inhibitor abrogated caspase-3 activity. Our results indicate that,
      while activation of multiple caspases are involved in the execution phase of GTP
      depletion-induced apoptosis, caspase-2 appears to play the major role in the
      initiation of this program. This study revealed a novel, caspase-2 mediated form
      of apoptosis that may be consequent to impaired mitogenesis.

PMID- 11956152
TI  - Cbl, IRS-1, and IRS-2 mediate effects of rosiglitazone on PI3K, PKC-lambda, and
      glucose transport in 3T3/L1 adipocytes.
AB  - The thiazolidenedione, rosiglitazone, increases basal and/or insulin-stimulated
      glucose transport in various cell types by diverse but uncertain mechanisms that
      may involve insulin receptor substrate (IRS)-1-dependent PI3K. Presently, in
      3T3/L1 adipocytes, rosiglitazone induced sizable increases in basal glucose
      transport that were: dependent on PI3K, 3-phosphoinositide-dependent protein
      kinase-1 (PDK-1), and PKC-lambda; accompanied by increases in tyrosine
      phosphorylation of Cbl and Cbl-dependent increases in PI3K and PKC-lambda
      activity; but not accompanied by increases in IRS-1/2-dependent PI3K or protein
      kinase B activity. Additionally, rosiglitazone increased IRS-1 and IRS-2 levels,
      thereby enhancing insulin effects on IRS-1- and IRS-2-dependent PI3K and
      downstream signaling factors PKC-lambda and protein kinase B. Our findings
      suggest that Cbl participates in mediating effects of rosiglitazone on PI3K, PDK
      1, and PKC-lambda and the glucose transport system and that this Cbl-dependent
      pathway complements the IRS-1 and IRS-2 pathways for activating PI3K, PDK-1, and
      PKC-lambda during combined actions of rosiglitazone and insulin in 3T3/L1 cells.

PMID- 11956153
TI  - Differential expression of c-fos and tyrosine hydroxylase mRNA in the adrenal
      gland of the infant rat: evidence for an adrenal hyporesponsive period.
AB  - Rats exhibit a stress hyporesponsive period from postnatal day (PND) 4-14 in
      which the neonate displays a minimal corticosterone response to stress. We used
      the maternal deprivation model to test whether this adrenocortical
      hyporesponsiveness to stress results from a decrease in adrenal sensitivity to
      ACTH. Neonates (PND 6, 9, and 12) were injected ip with dexamethasone to block
      endogenous ACTH release, and 4 h later injected with graded doses of ACTH and
      killed. In another experiment, neonates were injected with isotonic saline and
      adrenal glands were collected at 30, 60, and 120 min post injection to examine c
      fos and tyrosine hydroxylase mRNA levels using in situ hybridization. Maternally
      deprived pups demonstrated elevated corticosterone levels at the two highest ACTH
      doses and showed a greater magnitude in glucocorticoid secretion compared with
      the nondeprived pups. Maternally deprived pups given a saline injection exhibited
      elevated basal and stress-induced levels of corticosterone, in contrast to the
      nondeprived pups that showed a minimal response. Strikingly, maternally deprived
      pups exhibited elevated levels of adrenocortical c-fos mRNA, whereas the
      nondeprived pups did not. In contrast, the pattern of c-fos gene expression in
      the adrenal medulla in both groups did not display any correlation with
      glucocorticoid secretion. Tyrosine hydroxylase gene expression in the adrenal
      medulla was observed in both nondeprived and maternally deprived pups, with the
      latter exhibiting an earlier response of greater magnitude. These results
      demonstrate that the suppression of steroidogenesis occurs directly in the
      adrenal cortex and provide further evidence for an adrenal hyporesponsive period
      in the rat.

PMID- 11956154
TI  - The endocytosis-linked protein dynamin associates with caveolin-1 and is tyrosine
      phosphorylated in response to the activation of a noninternalizing epidermal
      growth factor receptor mutant.
AB  - Several studies have shown that an EGF receptor C-terminal truncation at residue
      973 (CT973) attenuates ligand-induced receptor endocytosis and is associated with
      cell transformation. Previously, we have shown that EGF stimulation of murine
      B82L fibroblasts expressing CT973 EGF receptors can promote the tyrosine
      phosphorylation of caveolin-1, which is a major component of caveolae membranes.
      Because dynamin plays an essential role in receptor-mediated endocytosis via
      clathrin-coated pits and caveolae, and because dynamin has been localized to
      caveolae, we tested the hypothesis that dynamin associates with caveolin-1 and is
      differentially modified in response to the abnormal actions of internalization
      defective EGF receptors. We found that dynamin coimmunoprecipitates with caveolin
      1 in cells containing normal or CT973 EGF receptors, but EGF stimulated the
      tyrosine phosphorylation of dynamin only in cells expressing truncated/oncogenic
      EGF receptors. Maximum dynamin phosphorylation was observed within 15 min of EGF
      administration and decreased thereafter. Furthermore, phosphotyrosine-containing
      proteins in the dynamin immunocomplexes were observed to be reactive with
      anticaveolin-1 antibodies. The EGF receptor does not appear to directly
      phosphorylate dynamin because a Src antagonist, PP1, inhibited the EGF-induced
      tyrosine phosphorylation of dynamin at a concentration that does not block EGF
      receptor autophosphorylation. These results provide the first evidence that
      caveolin-1 and dynamin form a complex, and that the EGF-induced tyrosine
      phosphorylation of dynamin occurs via a Src inhibitor-sensitive signaling pathway
      that is associated with the aberrant actions induced by internalization-defective
      EGF receptors.

PMID- 11956155
TI  - Intracellular calcium mobilization in response to the activation of human wild
      type and chimeric gonadotropin receptors.
AB  - It is well established that LH action is mediated primarily by adenylate
      cyclase/cAMP. However, the role of inositol phosphate/calcium in LH signaling is
      less well established. We examined the effects of gonadotropins in primary
      culture human granulosa-lutein cells and in HEK293 cells transiently transfected
      with human wild-type or chimeric gonadotropin receptors. The intracellular free
      calcium concentration was measured using fura-2 microspectrofluorometric
      techniques. Human (h) LH (2-4 microg/ml) and CG (10 IU/ml) consistently evoked
      oscillatory calcium signals in HEK293 cells transfected with hLH receptor,
      whereas hFSH (2-4 microg/ml) failed to elicit any response. Conversely, both hLH
      and hFSH failed to elicit a calcium response from HEK293 cells transfected with
      hFSHR, indicating the specificity of the response to the LH receptor.
      Pretreatment of transfected HEK293 cells with pertussis toxin (100 ng/ml)
      attenuated all gonadotropin-evoked calcium mobilization. Studies with chimeric LH
      receptor showed that the sequence of the long extracellular portion of the
      receptor was not critical for stimulation of PLC activity, but maintained agonist
      binding specificity. The C-terminal sequence of the receptor was clearly
      important for the generation of the basal calcium oscillations, but the precise
      extent of the critical sequence has yet to be identified. Although various
      subdivisions of this region were capable of stimulating calcium transients, an
      intact carboxyl-terminal third of the receptor was required for normal and
      sustained intracellular calcium signaling. Our study unequivocally shows that the
      hLH receptor is coupled to the inositol phosphate/calcium signaling pathway via a
      pertussis toxin-sensitive G protein-coupled receptor.

PMID- 11956156
TI  - Transgenic mice expressing human fibroblast growth factor-19 display increased
      metabolic rate and decreased adiposity.
AB  - The fibroblast growth factors (FGFs), and the corresponding receptors, are
      implicated in more than just the regulation of epithelial cell proliferation and
      differentiation. Specifically, FGF23 is a regulator of serum inorganic phosphate
      levels, and mice deficient in FGF receptor-4 have altered cholesterol metabolism.
      The recently described FGF19 is unusual in that it is nonmitogenic and appears to
      interact only with FGF receptor-4. Here, we report that FGF19 transgenic mice had
      a significant and specific reduction in fat mass that resulted from an increase
      in energy expenditure. Further, the FGF19 transgenic mice did not become obese or
      diabetic on a high fat diet. The FGF19 transgenic mice had increased brown
      adipose tissue mass and decreased liver expression of acetyl coenzyme A
      carboxylase 2, providing two mechanisms by which FGF19 may increase energy
      expenditure. Consistent with the reduction in expression of acetyl CoA
      carboxylase 2, liver triglyceride levels were reduced.

PMID- 11956157
TI  - Activation of 5-HT(7) receptor in rat glomerulosa cells is associated with an
      increase in adenylyl cyclase activity and calcium influx through T-type calcium
      channels.
AB  - Serotonin (5-HT) stimulates aldosterone secretion from the rat adrenal gland
      through 5-HT(7) receptors. The aim of the present study was to investigate the
      transduction mechanisms associated with activation of 5-HT(7) receptors in rat
      glomerulosa cells. The stimulatory effect of 5-HT on aldosterone secretion and
      cAMP formation was significantly reduced by the 5-HT(7) receptor antagonist LY
      215840. Pretreatment of cells with the adenylyl cyclase inhibitor SQ 22536 or the
      PKA inhibitor H-89 markedly attenuated the effect of 5-HT on aldosterone
      secretion. Conversely, type 2 and 4 phosphodiesterase inhibitors potentiated the
      5-HT-induced stimulation of aldosterone secretion. Administration of 5-HT in the
      vicinity of cultured glomerulosa cells induced a slowly developing and robust
      increase in cytosolic calcium concentration ([Ca(2+)](i)). The effect of 5-HT on
      [Ca(2+)](i) was suppressed by mibefradil, a T-type calcium channel blocker. Patch
      clamp studies confirmed that 5-HT activated a T-type calcium current. Mibefradil
      also induced a dose-dependent inhibition of 5-HT-induced aldosterone secretion.
      The sequence of events associated with activation of 5-HT(7) receptors was
      investigated. The PKA inhibitor H-89 markedly attenuated both the [Ca(2+)](i)
      response and the activation of T-type calcium current induced by 5-HT. In
      contrast, reduction of the calcium concentration in the incubation medium did not
      affect 5-HT- induced cAMP formation. Preincubation of glomerulosa cells with
      cholera toxin abolished the stimulatory effect of 5-HT on aldosterone secretion,
      but pertussis toxin had no effect. Taken together, these data demonstrate that,
      in rat glomerulosa cells, activation of native 5-HT(7) receptors stimulates cAMP
      formation through a G(salpha) protein, which in turn provokes calcium influx
      through T-type calcium channels. Both the adenylyl cyclase/PKA pathway and the
      calcium influx are involved in 5-HT-induced aldosterone secretion.

PMID- 11956158
TI  - Hyperactivation of the hypothalamo-pituitary-adrenocortical axis in
      streptozotocin-diabetes is associated with reduced stress responsiveness and
      decreased pituitary and adrenal sensitivity.
AB  - Although increased hypothalamo-pituitary-adrenocortical (HPA) activity has been
      reported in diabetic patients, the mechanisms underlying hyperactivation are
      still unclear. We investigated whether alterations in pituitary, adrenal and/or
      glucocorticoid negative feedback sensitivity in diabetes are responsible for 1)
      the impaired HPA response to stress and 2) basal hyperactivation of the HPA axis.
      Normal control, untreated streptozotocin-diabetic and insulin-treated diabetic
      rats were chronically catheterized. Eight days following surgery, pituitary
      adrenal function was monitored throughout the day. Stress responsiveness was
      evaluated using 20 min of restraint on d 10. Thereafter, the rats were treated
      with CRH (0.5 microg/kg), ACTH(1-24) (75ng/kg) or dexamethasone (25 microg/kg) iv
      on d 12, 14, and 16 to evaluate pituitary, adrenal and glucocorticoid feedback
      sensitivity, respectively. Plasma ACTH and corticosterone (B) concentrations in
      untreated diabetic rats were significantly higher at 0800 h, but no different at
      1300 h or 1800 h. Insulin treatment of diabetic rats normalized ACTH and B
      concentrations at 0800 h. The pituitary-adrenal response to restraint was greatly
      diminished in untreated diabetic rats, whereas insulin treatment partially
      restored this response in diabetic rats. Administration of CRH and ACTH revealed
      reduced pituitary and adrenal sensitivity in untreated diabetic animals compared
      with both control and insulin-treated diabetic animals. The dexamethasone
      suppression test indicated decreased glucocorticoid negative feedback sensitivity
      in diabetic rats, which was restored with insulin treatment. In conclusion, these
      studies demonstrate that: 1) impaired stress responsiveness of the diabetic HPA
      axis involves both decreased pituitary and adrenal sensitivity; and 2) basal
      hyperactivation of the diabetic HPA axis in the morning is due, in part, to
      decreased glucocorticoid negative feedback sensitivity.

PMID- 11956160
TI  - Differential activation of the IGF binding protein-3 promoter by butyrate in
      prostate cancer cells.
AB  - Sodium butyrate (NaB), a dietary micronutrient, is a potent growth inhibitor that
      initiates cell differentiation in many cell types, including prostate cancer
      cells. The molecular mechanisms by which these effects occur remain largely
      unknown. In this study, we investigated the effects of NaB on the expression of
      IGF binding protein (IGFBP)-3, a known growth regulator, in two human prostate
      cancer cell lines (PC-3 and LNCaP). Treatment with NaB (0-10 mM) caused a dose
      dependent stimulation of IGFBP-3 mRNA expression and parallel increases in
      protein levels. A specific histone deacetylase inhibitor, trichostatin A (TSA)
      similarly induced IGFBP-3 expression, indicating that histone hyperacetylation
      may be critical in the regulation of IGFBP-3 expression. To investigate the
      molecular mechanism of NaB-regulated IGFBP-3 expression, 1.87 kb of the human
      IGFBP-3 gene promoter was cloned into the pGL2-basic luciferase reporter vector.
      In both PC-3 and LNCaP cells, NaB (10 mM) significantly increased luciferase
      activity 20- to 30-fold, compared with the untreated control. However, using 5'
      sequential deletion constructs of the IGFBP-3 promoter, the NaB response
      sequences in the IGFBP-3 promoter were different in PC-3 and LNCaP cells. Our
      studies identified a region, -75 to +69 from the start of transcription (+1),
      that is fully inducible by NaB treatment in LNCaP cells, but not in PC-3 cells.
      Unlike other well characterized NaB-regulated genes, Sp1 DNA sequences are not
      involved in NaB up-regulation of IGFBP-3 gene in LNCaP cells. Further deletion
      studies identified two independent regions critical for NaB-induced
      transactivation in LNCaP cells. These regions contain consensus binding sites for
      p53 and GATA, respectively, but mutational analyses and gel shift assays
      suggested that, while the p53 response element is required for NaB
      responsiveness, neither p53 nor GATA are involved. In summary, we have
      demonstrated that 1) NaB significantly up-regulates IGFBP-3 mRNA and protein
      levels in PC-3 and LNCaP prostate cancer cells; and 2) novel butyrate- responsive
      elements lacking consensus Sp1 sites are used in LNCaP cells.

PMID- 11956159
TI  - Adrenocorticotropin/cyclic adenosine 3',5'-monophosphate-mediated transcription
      of the human CYP17 gene in the adrenal cortex is dependent on phosphatase
      activity.
AB  - cAMP-dependent transcription of steroid hydroxylase genes involves activation of
      cAMP-dependent protein kinase (PKA) and subsequent phosphorylation of downstream
      target proteins. Although the requirement for the activation of PKA is well
      established, none of the transcription factors required for steroid hydroxylase
      gene transcription have been found to be PKA phosphoproteins. In this study we
      examined the role of changes in phosphorylation state on the expression and
      transcriptional activity of the human CYP17 gene (hCYP17). Using inhibitors of
      serine/threonine phosphatase activity (okadaic acid) and phosphotyrosine
      phosphatase activity (peroxyvanadate), we can inhibit the cAMP-inducible binding
      of the steroidogenic factor-1 (SF-1), p54(nrb)/NonO, and polypyrimidine tract
      binding protein-associated splicing factor (PSF) complex required for regulation
      of transcription to the promoter of hCYP17. Further, both okadaic acid and
      peroxyvanadate attenuate cAMP-stimulated increases in endogenous hCYP17 mRNA
      expression and in hCYP17 promoter-reporter construct luciferase activity. In vivo
      phosphorylation and immunoprecipitation of SF-1 show a cAMP-stimulated decrease
      in (32)P-labeled SF-1. Our findings demonstrate that activation of protein
      phosphatase(s) is essential for cAMP-dependent transcription of hCYP17 in H295R
      cells and suggest a role for PKA in phosphatase activation, which leads to
      dephosphorylation of SF-1 and increased gene transcription.

PMID- 11956161
TI  - Concentrations of seven iodothyronine metabolites in brain regions and the liver
      of the adult rat.
AB  - The concentrations of the iodothyronine metabolites T(4), T(3), 3,5
      diiodothyronine (3,5-T(2)), 3,3'-diiodothyronine (3,3'-T(2)), reverse T(3)
      (rT(3)), 3,3'-T(2) sulfate (3,3'T(2)S), and T(3) sulfate (T(3)S) were measured in
      12 regions of the brain, the pituitary gland, and liver in adult male rats.
      Quantification of iodothyronine was performed by RIA following a newly developed
      method of purification and separation by HPLC. 3,5-T(2), 3,3'-T(2), rT(3) and
      T(2)S were detectable in the low femtomolar range (20-200 fmol/g) in most areas
      of the rat brain. T(3)S was detectable only in the hypothalamus. The
      concentrations of T(3) and T(4) were approximately 20- to 60-fold higher, ranging
      between 1 and 6 pmol/g. There was a significant negative correlation between the
      activities of inner-ring deiodinase and T(3) concentrations across brain areas.
      In the liver, 3,5-T(2), rT(3), and T(3)S were measurable in the low femtomolar
      range, whereas 3,3'-T(2) and 3,3'T(2)S were not detectable. 3,5-T(2) and 3,3'
      T(2) were not detectable in mitochondrial fractions of the brain regions. Tissue
      concentrations of 3,5-T(2) exhibited a circadian variation closely parallel to
      those of T(3) in the brain regions and liver. T(3) was not a substrate for outer
      ring deiodination under different experimental conditions; thus, it remains
      unclear which substrate(s) and enzyme(s) are involved in the production of 3,5
      T(2). These results indicate that five iodothyronine metabolites other than T(3)
      and T(4) are detectable in the low femtomolar range in the rat brain and/or
      liver. The physiological implications of this finding are discussed.

PMID- 11956162
TI  - Reproductive abnormalities in human IGF binding protein-1 transgenic female mice.
AB  - The mechanisms responsible for reproductive abnormalities in transgenic female
      mice overexpressing human IGF binding protein-1 (IGFBP-1) in the liver have been
      investigated. At 2 months of age, none of these transgenic mice exhibited ovarian
      cyclicity. Genital tract and ovary tissue weights were reduced in transgenic
      mice, this weight reduction being disproportionate with the reduction of body
      weight. Examination of ovarian follicular population revealed a marked decrease
      in the number of corpora lutea and gonadotropin-dependent follicles, suggesting
      an alteration of terminal follicular growth and ovulation. Stimulation of ovaries
      by exogenous gonadotropins revealed that ovaries from transgenic mice ovulated
      less oocytes than nontransgenic mice. This lower responsiveness of ovaries from
      transgenic mice to gonadotropins was not associated with a decrease in FSH-, LH-
      or IGF-I receptor expression. Transgenic and nontransgenic mice have similar
      circulating LH and FSH concentrations at dioestrus, after castration, 46 h after
      equine CG administration, or 15 min after GnRH injection. However, LH
      concentrations were 8-fold higher in pituitaries from transgenic vs.
      nontransgenic mice. Moreover, the size of LH-immunoreactive cells was reduced and
      their number was increased, suggesting a subtle alteration of LH secretion.
      Overall, these data indicate that reduced fertility in transgenic female mice
      overexpressing human IGFBP-1 are mainly due to an alteration of terminal
      follicular growth leading to a decrease in natural and induced ovulation rate,
      likely due to an impairment of IGF-I action on follicular cells. Increased
      circulating IGFBP-1 concentrations may additionally lead to altered GnRH and LH
      pulsatility and thereby exacerbate the ovulation defect.

PMID- 11956163
TI  - Prolonged stimulation of the adrenals by corticotropin suppresses hepatic low
      density lipoprotein and high-density lipoprotein receptors and increases plasma
      cholesterol.
AB  - Pituitary ACTH has been shown to strongly stimulate adrenal receptors for low
      density lipoprotein (LDL) and high-density lipoprotein (HDL) scavenger receptor
      class B type 1(SR-BI) to provide precursor cholesterol for glucocorticoid
      synthesis. The present study aimed to determine the effects of ACTH on hepatic
      cholesterol metabolism and plasma lipoproteins. Treatment of Sprague Dawley rats
      or normal C57BL/6J mice with ACTH for 3.5 d reduced hepatic SR-BI and LDL
      receptors. Simultaneously, cholesterol in plasma LDL and HDL was increased. None
      of these effects could be reproduced using glucocorticoids instead of ACTH, and
      they were abolished in adrenalectomized rats, indicating an obligate role of the
      adrenals for the effects of ACTH observed in the liver. When ACTH was given to
      LDL receptor-deficient mice, plasma LDL did not increase and the increase in HDL
      cholesterol remained, as did the suppression of hepatic SR-BI. Our data show that
      prolonged ACTH treatment suppresses hepatic SR-BI and LDL receptors in vivo in
      rodents, resulting in elevated plasma HDL and LDL. The adrenals are obligate for
      these effects, suggesting that ACTH releases some factor(s) that suppresses
      hepatic LDL and SR-BI receptors. Hypothetically, this novel mechanism would
      further promote channeling of cholesterol to the adrenals in situations of
      prolonged stress.

PMID- 11956164
TI  - Involvement of Rab27b in the regulated secretion of pituitary hormones.
AB  - We recently identified a novel set of Rab and its effector, Rab27a/granuphilin,
      that possibly regulates the exocytosis of insulin-containing, dense core granules
      in pancreatic beta-cells. In the present study we characterized another isoform,
      Rab27b, to further investigate the function of the Rab27 subfamily. Among the
      tissues examined, Rab27b is most abundantly expressed in pituitary tissue, where
      Rab27a is preferentially expressed. It is also significantly expressed in brain
      and spleen, where Rab27a is minimally expressed. Rab27a and Rab27b are
      differentially expressed in pituitary cell types that secrete different peptide
      hormones. Rab27b associates with secretory granules and granuphilin in the
      pituitary endocrine cell line AtT20. Furthermore, overexpression of its inactive
      mutant, Rab27b N133I, significantly inhibits basal and forskolin-induced ACTH
      secretion in AtT20 cells. These findings indicate that Rab27b is involved in
      pituitary hormone secretion, which further supports the idea that members of the
      Rab27 subfamily regulate the exocytosis of dense core granules containing peptide
      hormones in endocrine cells.

PMID- 11956165
TI  - Bcl-2 protein expression correlates with cell survival and androgen independence
      in rat prostatic lobes.
AB  - Castration of young and old male Brown Norway rats induces apoptosis in the
      ventral, but not in the dorsal and lateral, lobes of the prostate gland, and
      apoptosis in old rats is diminished by 50% compared with that in young rats. In
      this study we examined the lobe-specific and age-dependent expression of Bcl-2
      and Bax proteins. Bcl-2 levels in the ventral lobe were 5-fold lower compared
      with expression in the dorsal and lateral lobes. Bax expression in the ventral
      lobe was 2- and 20-fold higher than that in the lateral and dorsal lobes,
      respectively. In all three lobes, Bcl-2 was detected in epithelial cells, but not
      in stromal cells, whereas Bax protein was localized in both cell types. After
      castration, Bcl-2 expression in the ventral lobe decreased significantly from the
      control level after 2-3 d, but increased significantly by 7-10 d. By contrast,
      Bax expression increased significantly by d 1, gradually decreased by 2-4 d, and
      was nearly undetectable by 7-10 d postcastration. In the dorsal and lateral
      lobes, neither Bcl-2 nor Bax expression was significantly altered after
      castration. In the ventral lobe of old rats after castration, Bcl-2 followed a
      pattern of expression similar to that observed in young rats. However, Bax levels
      were 50% lower in old rats compared with those in young rats on d 1 after
      castration. Therefore, cell death follows the down-regulation of Bcl-2 expression
      in the ventral lobe of young and old rats. Moreover, the higher relative levels
      of Bcl-2 expression in the dorsal and lateral lobes of intact animals and in the
      ventral lobe by 7-10 d after castration serve to protect cells from apoptosis.

PMID- 11956166
TI  - The regulated expression of the pregnancy-associated plasma protein-A in the
      rodent ovary: a proposed role in the development of dominant follicles and of
      corpora lutea.
AB  - Compelling evidence exists displaying that the intrafollicular IGF-I system
      constitutes an obligatory mediator of FSH action in the murine ovary. Within this
      system, the ovarian IGF binding protein-4-directed protease (IGFBP-4ase) may have
      a critical role. Human IGFBP-4ase has been proved identical to the previously
      well-characterized pregnancy-associated plasma protein-A (PAPP-A). This
      communication reports the cloning and sequencing of the mouse PAPP-A cDNA as well
      as its expression and cellular localization in the mouse ovary. PAPP-A mRNA was
      undetectable in ovaries of untreated immature 25-d-old mice. Treatment with PMSG
      led to a marked time-dependent increase in PAPP-A expression in well-defined
      subsets of granulosa cells and follicles. Specifically, PAPP-A expression was
      detectable exclusively in centrifugally residing membrana granulosa cells of
      antral follicles during a 3- to 36-h period post PMSG. PAPP-A expression then
      fell to nondetectable levels in dominant preovulatory follicles at 48 h post
      PMSG. Treatment of PMSG-primed mice with human CG caused a rapid reinduction of
      PAPP-A expression in granulosa cells of dominant follicles and was sustained at
      relatively high levels throughout the ovulation and luteinization. These results
      suggest a role for gonadotropin-stimulated PAPP-A gene expression in the
      physiologic processes of dominant follicle development, ovulation, and
      luteogenesis in the mammalian ovary. The early onset and extended duration of
      gonadotropin-dependent PAPP-A expression in granulosa cells may serve to degrade
      the antigonadotropin IGFBP-4. Accordingly, successful antral follicle
      development, ovulation, and corpus luteum formation may be contingent on an IGFBP
      4-deplete/PAPP-A-replete circumstance, hence resulting in an IGF-I-replete
      intrafollicular microenvironment.

PMID- 11956167
TI  - Establishment of cell lines with rat spermatogonial stem cell characteristics.
AB  - Spermatogonial cell lines were established by transfecting a mixed population of
      purified rat A(s) (stem cells), A(pr) and A(al) spermatogonia with SV40 large T
      antigen. Two cell lines were characterized and found to express Hsp90alpha and
      oct-4, specific markers for germ cells and A spermatogonia, respectively.
      Expression of c-kit, normally expressed in A spermatogonia from late A(al)
      spermatogonia onwards, could not be detected in either cell line. Furthermore, no
      expression of vimentin (Sertoli cell marker) and alpha-smooth muscle actin
      (peritubular cell marker) could be found. Upon transplantation of these cell
      lines into recipient mice, the cells were found to be able to migrate to the
      basement membrane and to colonize seminiferous tubules. Taken together, we
      conclude that our cell lines have spermatogonial stem cell characteristics. These
      first spermatogonial cell lines with stem cell characteristics can now be used to
      study spermatogonial gene expression in comparison with more advanced germ cells.

PMID- 11956168
TI  - The role of the resting zone in growth plate chondrogenesis.
AB  - In mammals, growth of long bones occurs at the growth plate, a cartilage
      structure that contains three principal layers: the resting, proliferative, and
      hypertrophic zones. The function of the resting zone is not well understood. We
      removed the proliferative and hypertrophic zones from the rabbit distal ulnar
      growth plate in vivo, leaving only the resting zone. Within 1 wk, a complete
      proliferative and hypertrophic zone often regenerated. Next, we manipulated
      growth plates in vivo to place resting zone cartilage ectopically alongside the
      proliferative columns. Ectopic resting zone cartilage induced a 90-degree shift
      in the orientation of nearby proliferative zone chondrocytes and seemed to
      inhibit their hypertrophic differentiation. Our findings suggest that resting
      zone cartilage makes important contributions to endochondral bone formation at
      the growth plate: 1) it contains stem-like cells that give rise to clones of
      proliferative chondrocytes; 2) it produces a growth plate-orienting factor, a
      morphogen, that directs the alignment of the proliferative clones into columns
      parallel to the long axis of the bone; and 3) it may also produce a morphogen
      that inhibits terminal differentiation of nearby proliferative zone chondrocytes
      and thus may be partially responsible for the organization of the growth plate
      into distinct zones of proliferation and hypertrophy.

PMID- 11956169
TI  - Structural, biochemical, and expression analysis of two distinct insulin-like
      growth factor I receptors and their ligands in zebrafish.
AB  - We have cloned and characterized cDNAs encoding the zebrafish IGF ligands and
      receptors. Sequence comparison showed that the primary structures of zebrafish
      IGF-I, IGF-II, and IGF-I receptors (IGF-IRs) have been highly conserved in
      vertebrates. In contrast to the presence of a single IGF-IR gene in mammals, two
      distinct IGF-IR genes, termed igf-1ra and igf-1rb, were found in zebrafish.
      Structural and phylogenetic analyses indicated that both genes are orthologous to
      the human igf-1r gene. Immunoprecipitation studies with specific antibodies
      showed that both IGF-IR genes are expressed and both receptors bind to IGFs and
      des(1-3)IGF-I, but not to insulin. The spatio-temporal expression patterns of the
      two IGF-IRs and their ligands were determined using a combination of RT-PCR,
      whole mount in situ hybridization, and immunocytochemistry. Transcripts for both
      IGF-I and -II mRNAs were found throughout embryogenesis in a ubiquitous manner.
      In adult tissues, IGF-I mRNA was more abundant in liver and testis, and its level
      was increased after GH treatment, whereas IGF-II mRNA was not regulated by GH.
      IGF-IRa and IGF-IRb mRNAs and proteins were expressed in overlapping spatial
      domains, but exhibited distinct temporal expression patterns. In particular, the
      relative level of IGF-IRa mRNA was low during early embryogenesis and increased
      in the hatched larva, whereas the situation was reversed for IGF-IRb mRNA. In
      adult zebrafish, the overall tissue distribution patterns of the two IGF-IRs were
      similar, but there were differences in their cellular localization and relative
      abundance in defined cells/regions. The differential expression pattern of IGF
      IRa and IGF-IRb suggest that they may play distinct roles in regulating the
      growth and development of zebrafish.

PMID- 11956170
TI  - Requirement for IGF-I in epidermal growth factor-mediated cell cycle progression
      of mammary epithelial cells.
AB  - Induction of cyclin proteins is required for progression of cells through the
      G(1)-S and G(2)-M cell cycle checkpoints and is a primary mechanism by which
      mitogens regulate cell cycle progression. IGF-I and the epidermal growth factor
      (EGF)-related ligands are mitogens for mammary epithelial cells in vitro and are
      essential for growth of the mammary epithelium during development. We report here
      that IGF-I in combination with EGF or TGFalpha is synergistic in promoting DNA
      synthesis in mammary epithelial cells in the intact mammary gland cultured in
      vitro. We further investigated the role of IGF-I and EGF in cyclin expression and
      cell cycle progression in the mammary gland and demonstrate that IGF-I and EGF
      induce expression of early G(1) cyclins. However, we show that IGF-I, but not
      EGF, induces late G(1) and G(2) cyclins and is required for mammary epithelial
      cells to overcome the G(1)-S checkpoint. These data demonstrate that IGF-I is
      essential for cell cycle progression in mammary epithelial cells and that it is
      required for EGF-mediated progression past the G(1)-S checkpoint in these cells.

PMID- 11956171
TI  - Parathyroid hormone inhibits c-Jun N-terminal kinase activity in rat osteoblastic
      cells by a protein kinase A-dependent pathway.
AB  - Treatment of osteoblastic cells with PTH initiates dual signaling cascades
      resulting in activation of both PKA and PKC. It has been shown that PTH either
      inhibits or stimulates ERKs depending on dose of the hormone; nevertheless, the
      ability of PTH to regulate other members of the MAPK family is unknown. Another
      member of this family, c-Jun-NH(2)-terminal kinase (JNK), is preferentially
      activated by cytokines and cellular stresses and plays a key role in regulating
      the activity of various transcription factors. We demonstrate that treatment of
      UMR 106-01 cells and rat calvarial osteoblasts with PTH (10(-8) M), N-terminal
      peptides of PTH that selectively activate PKA, or 8-bromo-cAMP (activates PKA)
      results in the inhibition of JNK activity from high basal levels. Examination of
      the upstream members of the JNK cascade revealed that both stress-activated
      protein kinase/extracellular signal-related kinase kinase 1/MAPK kinase 4 and
      MAPK/extracellular signal-related kinase kinase kinase 1 activities were also
      inhibited after treatment with PTH (10(-8) M). We conclude that treatment of
      osteoblastic cells with PTH is sufficient to inhibit high basal JNK activity by
      activation of the PKA signaling cascade.

PMID- 11956172
TI  - A glucocorticoid-responsive mutant androgen receptor exhibits unique ligand
      specificity: therapeutic implications for androgen-independent prostate cancer.
AB  - The cortisol/cortisone-responsive AR (AR(ccr)) has two mutations (L701H and
      T877A) that were found in the MDA PCa human prostate cancer cell lines
      established from a castrated patient whose metastatic tumor exhibited androgen
      independent growth. Cortisol and cortisone bind to the AR(ccr) with high
      affinity. In the present study, we characterized the structural determinants for
      ligand binding to the AR(ccr). Our data revealed that many of the C17, C19, and
      C21 circulating steroids, at concentrations that are found in vivo, functioned as
      effective activators of the AR(ccr) but had little or no activity via the wild
      type AR or GRalpha. Among the synthetic glucocorticoids tested, dexamethasone
      activated both GRalpha and AR(ccr), whereas triamcinolone was selective for
      GRalpha. In MDA PCa 2b cells, growth and prostate-specific antigen production
      were stimulated by potent AR(ccr) agonists such as cortisol or 9alpha
      fluorocortisol but not by triamcinolone (which did not bind to or activate the
      AR(ccr)). Of the potential antagonists tested, bicalutamide (casodex) and GR
      antagonist RU38486 showed inhibitory activity. We postulate that corticosteroids
      provide a growth advantage to prostate cancer cells harboring the promiscuous
      AR(ccr) in androgen-ablated patients and contribute to their transition to
      androgen-independence. We predict that triamcinolone, a commonly prescribed
      glucocorticoid, would be a successful therapeutic agent for men with this form of
      cancer, perhaps in conjunction with the antagonist casodex. We hypothesize that
      triamcinolone administration would inhibit the hypothalamic-pituitary-adrenal
      axis, thus suppressing endogenous corticosteroids, which stimulate tumor growth.
      Triamcinolone, by itself, would not activate the AR(ccr) or promote tumor growth
      but would provide glucocorticoid activity essential for survival.

PMID- 11956173
TI  - Functional integrity of ErbB-4/-2 tyrosine kinase receptor complex in the
      hypothalamus is required for maintaining normal reproduction in young adult
      female rats.
AB  - ErbB-1 tyrosine kinase receptors are necessary for maintaining female
      reproduction by modulating the release of LH-releasing hormone (LHRH). Changes in
      ErbB-1 signaling capacity in aging rats are linked to compromised reproduction.
      The interactive and synergistic nature of different members of ErbB receptors in
      mediating signal transduction exists in many cellular systems. Particularly, the
      interactions among ErbB-1 and ErbB-2 or ErbB-4 and ErbB-2 are known to be
      involved in the stimulation of LHRH secretion during sexual maturation. Thus,
      ErbB-4/-2 receptors may also play a role in maintaining reproduction during
      adulthood, and consequently, alteration in ErbB-4/-2 signaling capacity may
      contribute to compromised reproductive competence during aging. By in situ
      hybridization histochemistry, ErbB-4/-2 mRNAs were detected in the preoptic area
      (POA) and arcuate nucleus, which are important areas involved in the control of
      LHRH neuronal activity. RT-PCR analyses showed that levels of ErbB-4/-2 mRNA
      increased to a maximal value in the POA of young adult animals before the LH
      surge. However, no such increase was found in middle-aged female rats. The timing
      of the decrease in ErbB-4 mRNA in the median eminence-arcuate nucleus of middle
      aged rats was delayed compared with that in young adult animals. Disruption of
      functional ErbB-4/-2 receptor complex by blocking ErbB-2 receptor synthesis in
      the hypothalamus via an infusion of ErbB-2 antisense oligodeoxynucleotide
      resulted in an estrous acyclicity in young adult rats. These results indicate
      that changes in ErbB-4/-2 gene expression and functional integrity of this ErbB
      4/-2 receptor complex in the hypothalamus of middle-aged female animals may lead
      to an altered preovulatory LH release. Thus, the ErbB-4/-2 receptor complex is a
      physiological component necessary for maintaining female reproduction.

PMID- 11956174
TI  - Transcriptional activity of nuclei in multinucleated osteoclasts and its
      modulation by calcitonin.
AB  - The function of osteoclasts is to digest the calcified bone matrix. Osteoclasts,
      together with myotubes, are among the rare examples of multinucleated cells found
      in higher vertebrates, resulting from the fusion of mononucleated progenitors
      belonging to the monocyte/macrophage lineage. So far, no information is available
      about function and transcriptional activity of multiple nuclei in osteoclasts. We
      have used a run-on technique to visualize RNA synthesis in individual nucleus. We
      provide the first evidence that nuclei of resorbing osteoclasts, isolated from
      chick embryo long bones, or differentiated in vitro from murine spleen cells in
      presence of RANKL and macrophage-colony stimulating factor, are all
      transcriptionally active. Nevertheless, if transcriptional activity is the same
      for all the nuclei within a cell, its level varies between osteoclasts:
      osteoclasts with highly active nuclei are always associated with resorption pits.
      We found that global transcription activity of resorbing osteoclasts seeded on
      calcified matrix is down-regulated after 5-h treatment with calcitonin, which
      transiently blocks resorption. This effect is reversible because calcitonin
      removal led to nuclear transcription activation. These results indicate a strong
      correlation between transcription and resorption. Finally, our data indicate that
      the resorption pit surface is linearly related to the nuclei number per
      osteoclast, strongly suggesting that functional advantage of osteoclast
      multinucleation is to improve resorption efficiency.

PMID- 11956175
TI  - Leptin promotes the development of mouse preimplantation embryos in vitro.
AB  - Leptin acts as a modulator of diverse reproductive functions, and recent studies
      have implicated involvement of leptin in the early embryo development in mammal.
      The aim of this study was to investigate the expression of leptin and its
      receptor (OB-R) in mouse oocyte and preimplantation embryo, and to examine
      whether leptin influenced the early embryo development. Leptin mRNA was detected
      in blastocyst and hatched blastocyst, and two splice variants of OB-R (OB-Ra and
      OB-Rb) mRNAs were detected in oocytes, 1-cell, 2-cell, morula, blastocyst, and
      hatched blastocyst. As for the origin of leptin, both leptin mRNA and protein
      were identified in the oviduct epithelium and endometrium of pregnant mouse. In
      the pregnant mouse, the levels of leptin in uterine fluid were higher than those
      in nonpregnant mouse. Addition of leptin to embryo culture media promotes the
      development from 2-cell stage embryos to the blastocysts, fully expanded
      blastocysts and hatched blastocysts. This effect was neutralized by an antibody
      against the extracellular domain of OB-R. Leptin significantly increased the
      total cell number of blastocysts, and the effect was preferentially observed in
      the trophectoderm. These findings raise the possibility of a paracrine/autocrine
      leptin signaling system regulating the development of mouse preimplantation
      embryo.

PMID- 11956176
TI  - Cyclosporine a and FK506 inhibit transcriptional activity of the human
      mineralocorticoid receptor: a cell-based model to investigate partial aldosterone
      resistance in kidney transplantation.
AB  - Renal transplant recipients treated with cyclosporine A (CsA) and FK506
      (tacrolimus) develop signs of hypoaldosteronism despite normal plasma aldosterone
      levels, suggesting a relative resistance of the distal nephron to aldosterone
      action. To examine the effects of immunosuppressants on human MR (hMR) function,
      we established the M cell model, renal tubular cells stably transfected with hMR.
      Upon CsA and FK506 administration, hMR mRNA levels and aldosterone binding in M
      cells remained unchanged (maximum number of sites, approximately 80 fmol/mg
      protein; K(d) = approximately 1 nM). Aldosterone-dependent intracellular
      localization of green fluorescent protein-hMR was not affected by
      immunosuppressants. A major impact of CsA or FK506 on the multidrug resistance
      gene product in cellular accumulation of aldosterone was also excluded. In
      contrast, aldosterone-stimulated hMR transcriptional activity was reduced to 53
      +/- 11.2% (P < 0.03) after pretreatment of M cells for 3 d with CsA and to 71 +/-
      9.6% (P < 0.05) after pretreatment with FK506. These effects were both time and
      concentration dependent (IC(50) of CsA, 10(-6) M; IC(50) of FK506, 10(-5) M) and
      needed at least 2 d to develop. Such an inhibitory effect does not depend on the
      N-terminal part of hMR, as CsA also reduced transcriptional activity of a 1-453
      deletion mutant of hMR. Our results demonstrate that immunosuppressants inhibit
      hMR transcriptional activity without affecting hMR expression, aldosterone
      binding properties, and hMR nucleocytoplasmic trafficking. They suggest that ion
      transport alterations in renal graft recipients are in part induced by impaired
      hMR function.

PMID- 11956177
TI  - Rescue of the osteopetrotic defect in op/op mice by osteoblast-specific targeting
      of soluble colony-stimulating factor-1.
AB  - Soluble colony-stimulating factor-1 (sCSF-1) and membrane bound CSF-1 are
      synthesized by osteoblasts and stromal cells. However, the precise role of each
      form in osteoclastogenesis is unclear. In the op/op mouse, absence of osteoblast
      derived CSF-1 leads to decreased osteoclasts and osteopetrosis. To determine
      whether sCSF-1 gene replacement can cure the osteopetrotic defect, we took
      advantage of the osteoblast specificity of the osteocalcin promoter to
      selectively express sCSF-1 in the bone of op/op mice. Transgenic mice harboring
      the human sCSF-1 cDNA under the control of the osteocalcin promoter were
      generated and cross-bred with heterozygous op/wt mice to establish op/op mutants
      expressing the transgene (op/opT). The op/op genotype and transgene expression
      were confirmed by PCR and Southern blot analysis, respectively. High levels of
      human sCSF-1 protein were selectively expressed in bone. At 2(1/2) wk, op/opT
      mice showed normal growth and tooth eruption. Femurs removed at 5 and 14 wk were
      analyzed by peripheral quantitative computed tomography and histomorphometry. The
      abnormal bone mineral density, cancellous bone volume, and growth plate width
      observed in op/op mice was completely reversed in op/opT mice by 5 wk, and this
      effect persisted at 14 wk, with measurements comparable with wt/wt mice at each
      time point. Correction of the skeletal abnormalities in the 5-wk-old op/opT mice
      correlated with a marked increase in the total osteoclast number, and their
      number per millimeter of bone surface compared with that of op/op mutants.
      Osteoclast number was maintained at 14 wk in op/opT mice and morphologically
      resembled wt/wt osteoclasts. These results indicate that sCSF-1 is sufficient to
      drive normal osteoclast development and that the osteocalcin promoter provides an
      efficient tool for delivery of exogenous genes to the bone. Moreover, targeting
      sCSF-1 to osteoblasts in the bone microenvironment may be a potentially useful
      therapeutic modality for treating bone disorders.

PMID- 11956179
TI  - Is GHRH receptor essential to GHRP-2-induced GH secretion in primary cultured rat
      pituitary cells?
AB  - It is still controversial in rat whether the stimulation of GH secretion by GH
      releasing peptides (GHRP) requires both GHRP receptor (GHRP-R) and GH-releasing
      hormone receptor (GHRH-R). To clarify this issue, we have postulated that
      inhibition of GHS-R or GHRH-R gene transcription should block GHRP-2-induced GH
      secretion. Rat pituitary cells were incubated for 3 days in the presence or
      absence of antisense 18-mer phosphorothiate oligonucleotides (ONs) complementary
      to the codon region of GHS-R or GHRH-R mRNAs. A significant decrease in GHRH-R
      and GHS-R mRNA levels was found in corresponding antisense-treated cells compared
      with the control cells treated with sense ON. Treatment with antisense GHS-R ON
      reduced (but not abolished) GHRP-2-induced GH secretion although GHRH-induced GH
      secretion was not altered. GHRH-stimulated GH secretion was totally abolished by
      the treatment with antisense GHRH-R ON, whereas GHRP-2 induced GH secretion was
      not affected. Treatment of cells with both GHS-R and GHRH-2 ONs however
      completely inhibited GHRH and GHRP-2-stimulated GH secretion. These results
      suggest that GHRH-R is vital for GHRH-induced GH secretion but only partially
      involved in GHRP-2-stimulated GH secretion under the condition of down-regulation
      of GHS-R gene transcription.

PMID- 11956178
TI  - Neuropeptide Y inhibits the biosynthesis of sulfated neurosteroids in the
      hypothalamus through activation of Y(1) receptors.
AB  - We have recently shown that hydroxysteroid sulfotransferase (HST), the enzyme
      responsible for the biosynthesis of pregnenolone sulfate (Delta(5)PS) and
      dehydroepiandrosterone sulfate (DHEAS), is expressed in neurons located in the
      anterior preoptic area and the dorsal magnocellular nucleus of the frog
      diencephalon. As these two nuclei are richly innervated by NPY-immunoreactive
      fibers, we investigated the possible implication of NPY in the control of
      Delta(5)PS and DHEAS biosynthesis. Double labeling of frog brain sections
      revealed that 42% of the HST-immunoreactive perikarya in the diencephalon were
      contacted by NPY-containing fibers. In situ hybridization studies showed that
      Y(1) and Y(5) receptor mRNAs are expressed in the anterior preoptic area and the
      dorsal magnocellular nucleus. Pulse-chase experiments with (35)S-labeled 3'
      phosphoadenosine 5'-phosphosulfate as a sulfate donor demonstrated that frog NPY
      (fNPY) inhibited the conversion of [(3)H]Delta(5)P and
      [(3)H]dehydroepiandrosterone ([(3)H]DHEA) into [(3)H,(35)S]Delta(5)PS and
      [(3)H,(35)S]DHEAS by diencephalic explants. The inhibitory effect of fNPY on
      Delta(5)PS and DHEAS formation was mimicked by (pPYY) and [Leu(31),Pro(34)]pNPY,
      which is an agonist for non-Y(2) receptors in mammals, and was completely
      suppressed by the Y(1) receptor antagonist BIBP3226. Conversely, the Y(2)
      receptor agonist pNPY-(13-36) and the Y(5) receptor agonist [D-Trp(32)]pNPY did
      not significantly modify the biosynthesis of [(3)H,(35)S]Delta(5)PS and
      [(3)H,(35)S]DHEAS. The present study provides the first evidence for the
      innervation of neurosteroid-producing neurons by NPY fibers. Our data also
      demonstrate that NPY, acting via Y(1) receptors, exerts an inhibitory effect on
      the biosynthesis of sulfated neurosteroids.

PMID- 11956180
TI  - Short ghrelin peptides neither displace ghrelin binding in vitro nor stimulate GH
      release in vivo.
AB  - Ghrelin is an acylated peptide recently isolated from rat stomach that potently
      stimulates GH release in vitro and in vivo in rat and man. Ghrelin specifically
      activates the receptor for the growth hormone secretagogues (GHS-Rla), and it has
      been proposed as the endogenous ligand mimicked by these synthetic compounds.
      Very recently, it was shown in cells transfected with the GHS-Rla that short
      acylated peptides encompassing the first 4-5 residues of ghrelin were capable of
      increasing intracellular calcium almost as efficiently as the full-length
      ghrelin. In the present study, we demonstrate that truncated analogs of ghrelin
      are ineffective in stimulating GH release in neonatal rats and do not displace
      radiolabelled ghrelin from binding sites in membranes from human hypothalamus and
      pituitary. In conclusion, our data demonstrate that the ability of short ghrelins
      to stimulate the GHS-Rla in transfected cells is not predictive of their
      capability to stimulate GH secretion in vivo.

PMID- 11956181
TI  - Induction of angiogenesis by a fragment of human tyrosyl-tRNA synthetase.
AB  - The first step of protein synthesis is catalyzed by aminoacyl-tRNA synthetases.
      In addition, certain mammalian tRNA synthetases link protein synthesis to
      cytokine signaling pathways. In particular, human tyrosyl-tRNA synthetase (TyrRS)
      can be split by proteolysis into two fragments having distinct cytokine
      activities. One of the TyrRS fragments (mini TyrRS) contains features identical
      to those in CXC chemokines (like interleukin-8) that also act as angiogenic
      factors. Here mini TyrRS (but not full-length TyrRS) is shown to stimulate
      chemotaxis of endothelial cells in vitro and stimulate angiogenesis in each of
      two in vivo animal models. The angiogenic activity of mini TyrRS can be opposed
      by anti-angiogenic chemokines like IP-10. Thus, a biological fragment of human
      tyrosyl-tRNA synthetase links protein synthesis to regulation of angiogenesis.

PMID- 11956182
TI  - Tissue transglutaminase protects against apoptosis by modifying the tumor
      suppressor protein p110 Rb.
AB  - Tissue transglutaminase (TGase) is involved in the regulation of several
      biological events including cellular differentiation and apoptosis. The
      expression and activation of TGase are up-regulated in response to retinoic acid
      (RA), leading to the protection of several cell lines against N-(4
      hydroxyphenyl)retinamide (HPR)-induced apoptosis. The anti-apoptotic mechanisms
      of TGase are poorly understood at this time. We examined the interaction of TGase
      with the retinoblastoma (Rb) protein, a substrate of TGase that is also
      implicated in cell survival functions. In cells undergoing HPR-induced apoptosis,
      Rb is degraded. This degradation is blocked when cells are pretreated with RA, an
      important regulator of TGase. In vitro studies revealed that TGase protects Rb
      from caspase-induced degradation in a transamidation-dependent manner.
      Experiments performed with fibroblasts from Rb(-/-) mice further demonstrated
      that the presence of Rb was required for TGase to exhibit anti-apoptotic activity
      in response to RA treatment. Microinjection of Rb(-/-) cells with a
      transamidation-defective TGase mutant and Rb afforded no protection from HPR
      induced apoptosis. Taken together, these findings suggest that the ability of
      TGase to modify Rb via transamidation underlies the ability of TGase to provide
      protection against apoptotic insults and to ensure that cells remain viable
      during differentiation.

PMID- 11956183
TI  - The type XIII collagen ectodomain is a 150-nm rod and capable of binding to
      fibronectin, nidogen-2, perlecan, and heparin.
AB  - Type XIII collagen consists of a short N-terminal intracellular domain, a
      transmembrane domain, and a collagenous ectodomain, and it is found at many sites
      of cell adhesion. We report on the characterization of recombinant type XIII
      collagen. The shed ectodomain was purified from insect cell culture medium and
      shown to form 240-kDa trimers with a T(m) of 42 degrees C. Correct chain
      association into a triple-helical conformation was confirmed by limited pepsin
      digestion and CD spectroscopy. Rotary shadowing electron microscopy of the
      ectodomain revealed it to be a 150-nm rod with two flexible hinges separating 31
      , 52-, and 68-nm portions. The rods represent the collagenous domains 1-3, and
      the hinges coincide with the non-collagenous domains 2 and 3. By using surface
      plasmon resonance analysis, the ectodomain showed interaction with immobilized
      fibronectin, nidogen-2, and perlecan with K(D) values in the nanomolar range. The
      binding sites of type XIII collagen for fibronectin were localized to the
      collagenous domains, whereas the binding activities for nidogen-2 and perlecan
      resided in the pepsin-sensitive portions of the ectodomain. Furthermore, the
      ectodomain bound significantly to heparin, which also inhibited shedding of the
      ectodomain in insect cell cultures. The results reveal that type XIII collagen is
      notably distinct in its structure compared with other cell-surface proteins, and
      the in vitro binding with fibronectin, heparin, and two basement membrane
      components is indicative of multiple cell-matrix interactions in which this
      ubiquitously expressed protein participates.

PMID- 11956184
TI  - New signaling pathway for parathyroid hormone and cyclic AMP action on
      extracellular-regulated kinase and cell proliferation in bone cells. Checkpoint
      of modulation by cyclic AMP.
AB  - cAMP signaling, activated by extracellular stimuli such as parathyroid hormone,
      has cell type-specific effects important for cellular proliferation and
      differentiation in bone cells. Recent evidence of a second enzyme target for cAMP
      suggests divergent effects on extracellular-regulated kinase (ERK) activity
      depending on Epac/Rap1/B-Raf signaling. We investigated the molecular mechanism
      of the dual functionality of cAMP on cell proliferation in clonal bone cell
      types. MC3T3-E1 and ATDC5, but not MG63, express a 95-kDa isoform of B-Raf. cAMP
      stimulated Ras-independent and Rap1-dependent ERK phosphorylation and cell
      proliferation in B-Raf-expressing cells, but inhibited growth in B-Raf-lacking
      cells. The mitogenic action of cAMP was blocked by the ERK pathway inhibitor
      PD98059. In B-Raf-transduced MG63 cells, cAMP stimulated ERK activation and cell
      proliferation. Thus, B-Raf is the dominant molecular switch that permits
      differential cAMP-dependent regulation of ERK with important implications for
      cell proliferation in bone cells. These findings might explain the dual
      functionality of parathyroid hormone on osteoblastic cell proliferation.

PMID- 11956185
TI  - Transcriptional control of the human thromboxane synthase gene in vivo and in
      vitro.
AB  - Thromboxane A(2), a potent mediator of vasoconstriction and platelet aggregation,
      is synthesized from prostaglandin H(2) by thromboxane synthase (TXAS). We report
      here on promoter analyses of human TXAS using in vitro transcription and in vivo
      transfection methods. The 39-bp core promoter, containing both TATA and initiator
      elements, accurately initiates transcription in an orientation-dependent manner
      in a cell-free transcription system. Mutation of either TATA or initiator
      abolished transcriptional activity, but the upstream sequence had no effect on
      TXAS promoter activities in vitro, suggesting that the core promoter is
      sufficient for transcriptional activity from a naked DNA template. In contrast,
      mutation of both elements drastically decreased the promoter activity in vivo.
      Furthermore, TXAS proximal promoter containing the nucleotides -90 to -56
      relative to the transcriptional start site was necessary for promoter
      transactivation in vivo. Transcriptional activities from 5'-deletion mutants
      indicated that the effects of the nucleotides -90/-56 were more pronounced in
      stably transfected cells (a 150-fold difference) than in the transiently
      transfected cells (an 8-fold difference), reflecting the effects of TXAS
      transcriptional activation from replicating and nonreplicating DNA templates.
      Partial micrococcal nuclease digestion indicated that the sequence -90/-56, where
      the NF-E2 site is located, is associated with alterations of nucleosomal
      structure at the regions of promoter and reporter gene but not the region further
      downstream. Mutagenesis and forced expression studies demonstrated a critical
      role of p45 NF-E2 in controlling TXAS expression under native chromatin
      conditions. Band shifting and chromatin immunoprecipitation assays indicated that
      p45 NF-E2 was bound to the TXAS promoter in vitro and in vivo. Indirect end
      labeling and ligation-mediated PCR analyses further demonstrated that the
      occupation of TXAS promoter NF-E2 site was associated with disruption of
      nucleosomal structure. Collectively, these results indicate that binding of NF-E2
      is critical both for alteration of the nucleosomal structure and for activation
      of the TXAS promoter, whereas the TATA and initiator elements are essential for
      transcription.

PMID- 11956187
TI  - Biochemical characterization of the DNA substrate specificity of Werner syndrome
      helicase.
AB  - Werner syndrome is a hereditary premature aging disorder characterized by genome
      instability. The product of the gene defective in WS, WRN, is a
      helicase/exonuclease that presumably functions in DNA metabolism. To understand
      the DNA structures WRN acts upon in vivo, we examined its substrate preferences
      for unwinding. WRN unwound a 3'-single-stranded (ss)DNA-tailed duplex substrate
      with streptavidin bound to the end of the 3'-ssDNA tail, suggesting that WRN does
      not require a free DNA end to unwind the duplex; however, WRN was completely
      blocked by streptavidin bound to the 3'-ssDNA tail 6 nucleotides upstream of the
      single-stranded/double-stranded DNA junction. WRN efficiently unwound the forked
      duplex with streptavidin bound just upstream of the junction, suggesting that WRN
      recognizes elements of the fork structure to initiate unwinding. WRN unwound two
      important intermediates of replication/repair, a 5'-ssDNA flap substrate and a
      synthetic replication fork. WRN was able to translocate on the lagging strand of
      the synthetic replication fork to unwind duplex ahead of the fork. For the 5'
      flap structure, WRN specifically displaced the 5'-flap oligonucleotide,
      suggesting a role of WRN in Okazaki fragment processing. The ability of WRN to
      target DNA replication/repair intermediates may be relevant to its role in genome
      stability maintenance.

PMID- 11956186
TI  - The structural motif in chondroitin sulfate for adhesion of Plasmodium falciparum
      infected erythrocytes comprises disaccharide units of 4-O-sulfated and non
      sulfated N-acetylgalactosamine linked to glucuronic acid.
AB  - An important characteristic of malaria parasite Plasmodium falciparum-infected
      red blood cells (IRBCs) is their ability to adhere to host endothelial cells and
      accumulate in various organs. Sequestration of IRBCs in the placenta, associated
      with excess perinatal and maternal mortality, is mediated in part by adhesion of
      parasites to the glycosaminoglycan chondroitin sulfate A (CSA) present on
      syncytiotrophoblasts lining the placental blood spaces. To define key structural
      features for parasite interactions, we isolated from CSA oligosaccharide
      fractions and established by electrospray mass spectrometry and high performance
      liquid chromatography disaccharide composition analysis their differing chain
      length, sulfate content, and sulfation pattern. Testing these defined
      oligosaccharide fragments for their ability to inhibit IRBC adhesion to
      immobilized CSA revealed the importance of non-sulfated disaccharide units in
      combination with 4-O-sulfated disaccharides for interaction with IRBCs. Selective
      removal of 6-O-sulfates from oligo- and polysaccharides to increase the
      proportion of non-sulfated disaccharides enhanced activity, indicating that 6-O
      sulfation interferes with the interaction of CSA with IRBCs. Dodecasaccharides
      with four or five 4-O-sulfated and two or one non-sulfated disaccharide units,
      respectively, comprise the minimum chain length for effective interaction with
      IRBCs. Comparison of the activities of CSA and CSB oligo- and polysaccharides
      with a similar sulfation pattern and content achieved from partial desulfation
      demonstrated that glucuronic acid rather than iduronic acid residues are
      important for IRBC binding.

PMID- 11956188
TI  - The effect of stathmin phosphorylation on microtubule assembly depends on tubulin
      critical concentration.
AB  - Stathmin is a phosphorylation-regulated tubulin-binding protein. In vitro and in
      vivo studies using nonphosphorylatable and pseudophosphorylated mutants of
      stathmin have questioned the view that stathmin might act only as a tubulin
      sequestering factor. Stathmin was proposed to effectively regulate microtubule
      dynamic instability by increasing the frequency of catastrophe (the transition
      from steady growth to rapid depolymerization), without interacting with tubulin.
      We have used a noninvasive method to measure the equilibrium dissociation
      constants of the T(2)S complexes of tubulin with stathmin, pseudophosphorylated
      (4E)-stathmin, and diphosphostathmin. At both pH 6.8 and pH 7.4, the relative
      sequestering efficiency of the different stathmin variants depends on the
      concentration of free tubulin, i.e. on the dynamic state of microtubules. This
      control is exerted in a narrow range of tubulin concentration due to the highly
      cooperative binding of tubulin to stathmin. Changes in pH affect the stability of
      tubulin-stathmin complexes but do not change stathmin function. The 4E-stathmin
      mutant mimics inactive phosphorylated stathmin at low tubulin concentration and
      sequesters tubulin almost as efficiently as stathmin at higher tubulin
      concentration. We propose that stathmin acts solely by sequestering tubulin,
      without affecting microtubule dynamics, and that the effect of stathmin
      phosphorylation on microtubule assembly depends on tubulin critical
      concentration.

PMID- 11956189
TI  - Cyclin G2 associates with protein phosphatase 2A catalytic and regulatory B'
      subunits in active complexes and induces nuclear aberrations and a G1/S phase
      cell cycle arrest.
AB  - Cyclin G2, together with cyclin G1 and cyclin I, defines a novel cyclin family
      expressed in terminally differentiated tissues including brain and muscle. Cyclin
      G2 expression is up-regulated as cells undergo cell cycle arrest or apoptosis in
      response to inhibitory stimuli independent of p53 (Horne, M., Donaldson, K.,
      Goolsby, G., Tran, D., Mulheisen, M., Hell, J. and Wahl, A. (1997) J. Biol. Chem.
      272, 12650-12661). We tested the hypothesis that cyclin G2 may be a negative
      regulator of cell cycle progression and found that ectopic expression of cyclin
      G2 induces the formation of aberrant nuclei and cell cycle arrest in HEK293 and
      Chinese hamster ovary cells. Cyclin G2 is primarily partitioned to a detergent
      resistant compartment, suggesting an association with cytoskeletal elements. We
      determined that cyclin G2 and its homolog cyclin G1 directly interact with the
      catalytic subunit of protein phosphatase 2A (PP2A). An okadaic acid-sensitive (<2
      nm) phosphatase activity coprecipitates with endogenous and ectopic cyclin G2. We
      found that cyclin G2 also associates with various PP2A B' regulatory subunits, as
      previously shown for cyclin G1. The PP2A/A subunit is not detectable in cyclin G2
      PP2A-B'-C complexes. Notably, cyclin G2 colocalizes with both PP2A/C and B'
      subunits in detergent-resistant cellular compartments, suggesting that these
      complexes form in living cells. The ability of cyclin G2 to inhibit cell cycle
      progression correlates with its ability to bind PP2A/B' and C subunits. Together,
      our findings suggest that cyclin G2-PP2A complexes inhibit cell cycle
      progression.

PMID- 11956190
TI  - Sphingosine 1-phosphate induces membrane ruffling and increases motility of human
      umbilical vein endothelial cells via vascular endothelial growth factor receptor
      and CrkII.
AB  - Sphingosine 1-phosphate (S1P), a ligand for endothelial differentiation gene
      family proteins, is one of the most potent signal mediators released from
      activated platelets. Here, we report that S1P induces membrane ruffling of human
      umbilical vein endothelial cells (HUVECs) via the vascular endothelial growth
      factor receptor (VEGFR), Src family tyrosine kinase(s), and the CrkII adaptor
      protein. S1P induced prominent phosphorylation of CrkII in HUVECs, indicating
      that CrkII was involved in the S1P-induced signaling pathway. S1P-induced CrkII
      phosphorylation was blocked by pertussis toxin and overexpression of the carboxyl
      terminus of beta-adrenergic receptor kinase, indicating that the betagamma
      subunit of G(i) was required for the phosphorylation. Notably, the S1P-induced
      CrkII phosphorylation was also abolished by inhibitors of VEGFR or Src family
      tyrosine kinases. By using Picchu, a real time monitoring protein for CrkII
      phosphorylation, we found that S1P induced rapid CrkII phosphorylation at
      membrane ruffles. Finally, we observed that expression of a dominant negative
      mutant of CrkII inhibited the S1P-induced membrane ruffling and cell migration.
      These results delineated a novel S1P signaling pathway that involves sequential
      activation of G(i)-coupled receptor(s), VEGFR, Src family tyrosine kinase(s), and
      the CrkII adaptor protein, and which is responsible for both the induction of
      membrane ruffling and the increase in cell motility.

PMID- 11956191
TI  - The carboxyl termini of K(ATP) channels bind nucleotides.
AB  - ATP-sensitive potassium (K(ATP)) channels are expressed in many excitable, as
      well as epithelial, cells and couple metabolic changes to modulation of cell
      activity. ATP regulation of K(ATP) channel activity may involve direct binding of
      this nucleotide to the pore-forming inward rectifier (Kir) subunit despite the
      lack of known nucleotide-binding motifs. To examine this possibility, we assessed
      the binding of the fluorescent ATP analogue, 2',3'-O-(2,4,6-trinitrophenylcyclo
      hexadienylidene)adenosine 5'-triphosphate (TNP-ATP) to maltose-binding fusion
      proteins of the NH(2)- and COOH-terminal cytosolic regions of the three known
      K(ATP) channels (Kir1.1, Kir6.1, and Kir6.2) as well as to the COOH-terminal
      region of an ATP-insensitive inward rectifier K(+) channel (Kir2.1). We show
      direct binding of TNP-ATP to the COOH termini of all three known K(ATP) channels
      but not to the COOH terminus of the ATP-insensitive channel, Kir2.1. TNP-ATP
      binding was specific for the COOH termini of K(ATP) channels because this
      nucleotide did not bind to the NH(2) termini of Kir1.1 or Kir6.1. The affinities
      for TNP-ATP binding to K(ATP) COOH termini of Kir1.1, Kir6.1, and Kir6.2 were
      similar. Binding was abolished by denaturing with 4 m urea or SDS and enhanced by
      reduction in pH. TNP-ATP to protein stoichiometries were similar for all K(ATP)
      COOH-terminal proteins with 1 mol of TNP-ATP binding/mole of protein. Competition
      of TNP-ATP binding to the Kir1.1 COOH terminus by MgATP was complex with both
      Mg(2+) and MgATP effects. Glutaraldehyde cross-linking demonstrated the
      multimerization potential of these COOH termini, suggesting that these cytosolic
      segments may directly interact in intact tetrameric channels. Thus, the COOH
      termini of K(ATP) tetrameric channels contain the nucleotide-binding pockets of
      these metabolically regulated channels with four potential nucleotide-binding
      sites/channel tetramer.

PMID- 11956192
TI  - Characterization of three fragments that constitute the monomers of the human
      lysyl hydroxylase isoenzymes 1-3. The 30-kDa N-terminal fragment is not required
      for lysyl hydroxylase activity.
AB  - Lysyl hydroxylase (LH) catalyzes the formation of hydroxylysine in collagens;
      three human isoenzymes have been cloned so far. We report here on the
      purification of all three recombinant isoenzymes to homogeneity from the medium
      of cultured insect cells, and we demonstrate that they are all homodimers.
      Limited proteolysis experiments identified two main protease-sensitive regions in
      the monomers of about 80-85 kDa, corresponding to three fragments A-C (from the N
      to C terminus), with molecular masses of about 30, 37, and 16 kDa, respectively.
      Fragment A was found to play no role in LH activity as a recombinant B-C
      polypeptide constituted a fully active hydroxylase with K(m) values for
      cosubstrates and the peptide substrate that were identical to those of the full
      length enzyme. LH3, but not LH1 and LH2, has also been reported recently
      (Heikkinen, J., Risteli, M., Wang, C., Latvala, J., Rossi, M., Valtavaara, M.,
      and Myllyla, R. (2000) J. Biol. Chem. 275, 36158-36163) to possess collagen
      glucosyltransferase activity. We confirm this highly surprising finding here and
      extend it by demonstrating that LH3 may also possess trace amounts of collagen
      galactosyltransferase activity. All the glucosyltransferase and
      galactosyltransferase activity of LH3 was found to reside in fragment A, which
      played no role in the hydroxylase activity of the polypeptide. This fragment is
      about 55% identical and 80% similar to the corresponding fragments of LH1 and
      LH2. However, the levels of the glycosyltransferase activities are so low that
      they may be of little biological significance. It is thus evident that human
      tissues must have additional glycosyltransferases that are responsible for most
      of the collagen glycosylation in vivo.

PMID- 11956193
TI  - Inhibition of ADAM-TS4 and ADAM-TS5 prevents aggrecan degradation in
      osteoarthritic cartilage.
AB  - Osteoarthritis is a degenerative joint disorder characterized by breakdown of
      articular cartilage. Degradation of aggrecan, which together with type II
      collagen provides cartilage with its unique characteristics of compressibility
      and elasticity, is an early and sustained feature of osteoarthritis. The present
      work was set up to identify the enzyme(s) responsible for aggrecan breakdown in
      osteoarthritis. We found that the two cartilage aggrecanases, ADAM-TS4 and ADAM
      TS5, are present in osteoarthritic cartilage and that they are responsible for
      aggrecan degradation without the participation of matrix metalloproteinases. This
      is based on 1) neoepitopes found on aggrecan fragments in osteoarthritis (OA)
      cartilage explants in vitro, 2) aggrecan fragments detected in synovial fluid of
      OA patients, 3) the observation that an aggrecanase inhibitor, BB-16, blocked
      aggrecan degradation in OA cartilage in vitro, whereas the matrix
      metalloproteinase inhibitor XS309 did not, and 4) the presence of mRNA and
      protein for ADAM-TS4 and ADAM-TS5 in OA cartilage. These results suggest that
      ADAM-TS4 and ADAM-TS5 represent a potential target for the treatment of
      osteoarthritis.

PMID- 11956194
TI  - Unique activation mechanism of protein kinase CK2. The N-terminal segment is
      essential for constitutive activity of the catalytic subunit but not of the
      holoenzyme.
AB  - CK2 is an essential, ubiquitous, and highly pleiotropic protein kinase whose
      catalytic subunits (alpha and alpha') and holoenzyme (composed by two catalytic
      and two regulatory beta-subunits) are both constitutively active, a property that
      is suspected to contribute to its pathogenic potential. Extensive interactions
      between the N-terminal segment and the activation loop are suspected to underlie
      the high constitutive activity of the isolated catalytic subunit. Here we show
      that a number of point mutations (Tyr(26) --> Phe, Glu(180) --> Ala, Tyr(182) -->
      Phe) and deletions (Delta 2-6, Delta 2-12, Delta 2-18, Delta 2-24, Delta 2-30)
      expected to affect these interactions are more or less detrimental to catalytic
      activity of the alpha-subunit of human CK2, the deleted mutants Delta 2-24 and
      Delta 2-30 being nearly inactive under normal assay conditions. Kinetic analyses
      showed that impaired catalytic activity of mutants Delta 2-12, Delta 2-18, Delta
      2-24, and Y182F is mainly accounted for by dramatic increases in the K(m) values
      for ATP, whereas a drop in K(cat) with K(m) values almost unchanged was found
      with mutants Y26F and E180A. Holoenzyme reconstitution restored the activity of
      mutants Delta 2-12, Delta 2-18, Y26F, E180A, and Y182F to wild type level and
      also conferred catalytic activity to the intrinsically inactive mutants, Delta 2
      24 and Delta 2-30. These data demonstrate that specific interactions between the
      N-terminal segment and the activation loop are essential to provide a fully
      active conformation to the catalytic subunits of CK2; they also show that these
      interactions become dispensable upon formation of the holoenzyme, whose
      constitutive activity is conferred by the beta-subunit through a different
      mechanism.

PMID- 11956195
TI  - Myb-binding protein 1a augments AhR-dependent gene expression.
AB  - We have studied the mechanism by which an acidic domain (amino acids 515-583) of
      the aromatic hydrocarbon receptor (AhR) transactivates a target gene. Studies
      with glutathione S-transferase fusion proteins demonstrate that the wild-type
      acidic domain associates in vitro with Myb-binding protein 1a, whereas a mutant
      domain (F542A, I569A) does not. AhR-defective cells reconstituted with an AhR
      containing the wild-type acidic domain exhibit normal AhR function; however,
      cells reconstituted with an AhR containing the mutant acidic domain do not
      function normally. Transient transfection of Myb-binding protein 1a into mouse
      hepatoma cells is associated with augmentation of AhR-dependent gene expression.
      Such augmentation does not occur when Myb-binding protein 1a is transfected into
      AhR-defective cells that have been reconstituted with an AhR that lacks the
      acidic domain. We infer that 1) Myb-binding protein 1a associates with AhR,
      thereby enhancing transactivation, and 2) the presence of AhR's acidic domain is
      both necessary and sufficient for Myb-binding protein 1a to increase AhR
      dependent gene expression.

PMID- 11956196
TI  - Identification of a cis-acting element for the regulation of SMN exon 7 splicing.
AB  - Spinal muscular atrophy results from the loss of functional survival motor neuron
      (SMN1) alleles. Two nearly identical copies of SMN exist and differ only by a
      single non-polymorphic C to T transition in exon 7. This transition leads to
      alteration of exon 7 splicing; that is, SMN1 produces a full-length transcript,
      whereas SMN2 expresses a low level of full-length transcript and predominantly an
      isoform lacking exon 7. The truncated transcript of SMN encodes a less stable
      protein with reduced self-oligomerization activity that fails to compensate for
      the loss of SMN1. In this paper, we identified a cis-acting element (element 1),
      which is composed of 45 bp in intron 6 responsible for the regulation of SMN exon
      7 splicing. Mutations in element 1 or treatment with antisense oligonucleotides
      directed toward element 1 caused an increase in exon 7 inclusion. An
      approximately 33-kDa protein was demonstrated to associate with a pre-mRNA
      sequence containing both element 1 and the C to T transition in SMN exon 7 but
      not with the sequence containing mutated element 1, suggesting that the binding
      of the approximately 33-kDa protein plays crucial roles in the skipping of SMN
      exon 7 containing the C to T transition.

PMID- 11956197
TI  - KpsF is the arabinose-5-phosphate isomerase required for 3-deoxy-D-manno
      octulosonic acid biosynthesis and for both lipooligosaccharide assembly and
      capsular polysaccharide expression in Neisseria meningitidis.
AB  - We have identified and defined the function of kpsF of Neisseria meningitidis and
      the homologues of kpsF in encapsulated K1 and K5 Escherichia coli. KpsF was shown
      to be the arabinose-5-phosphate isomerase, an enzyme not previously identified in
      prokaryotes, that mediates the interconversion of ribulose 5-phosphate and
      arabinose 5-phosphate. KpsF is required for 3-deoxy-d-manno-octulosonic acid
      (Kdo) biosynthesis in N. meningitidis. Mutation of kpsF or the gene encoding the
      CMP-Kdo synthetase (kpsU/kdsB) in N. meningitidis resulted in expression of a
      lipooligosaccharide (LOS) structure that contained only lipid A and reduced
      capsule expression in the five invasive disease-associated meningococcal
      serogroups (A, B, C, Y, and W-135). The step linking meningococcal capsule and
      LOS biosynthesis was shown to be Kdo production as the expression of capsule was
      wild type in a Kdo transferase (kdtA) mutant. Thus, in addition to
      lipooligosaccharide assembly, Kdo is required for meningococcal capsular
      polysaccharide expression. Furthermore, N. meningitidis, unlike enteric Gram
      negative bacteria, can survive and synthesize only unglycosylated lipid A.

PMID- 11956198
TI  - 15-Lipoxygenase metabolism of 2-arachidonylglycerol. Generation of a peroxisome
      proliferator-activated receptor alpha agonist.
AB  - The recent demonstrations that cyclooxygenase-2 and leukocyte-type 12
      lipoxygenase (LOX) efficiently oxygenate 2-arachidonylglycerol (2-AG) prompted an
      investigation into related oxygenases capable of metabolizing this endogenous
      cannabinoid receptor ligand. We evaluated the ability of six LOXs to catalyze the
      hydroperoxidation of 2-AG. Soybean 15-LOX, rabbit reticulocyte 15-LOX, human 15
      LOX-1, and human 15-LOX-2 oxygenate 2-AG, providing 15(S)
      hydroperoxyeicosatetraenoic acid glyceryl ester. In contrast, potato and human 5
      LOXs do not efficiently metabolize this endocannabinoid. Among a series of
      structurally related arachidonyl esters, arachidonylglycerols serve as the
      preferred substrates for 15-LOXs. Steady-state kinetic analysis demonstrates that
      both 15-LOX-1 and 15-LOX-2 oxygenate 2-AG comparably or preferably to arachidonic
      acid. Furthermore, 2-AG treatment of COS-7 cells transiently transfected with
      human 15-LOX expression vectors or normal human epidermal keratinocytes results
      in the production and extracellular release of 15-hydroxyeicosatetraenoic acid
      glyceryl ester (15-HETE-G), establishing that lipoxygenase metabolism of 2-AG
      occurs in an eukaryotic cellular environment. Investigations into the potential
      biological actions of 15-HETE-G indicate that this lipid, in contrast to its free
      acid counterpart, acts as a peroxisome proliferator-activated receptor alpha
      agonist. The results demonstrate that 15-LOXs are capable of acting on 2-AG to
      provide 15-HETE-G and elucidate a potential role for endocannabinoid oxygenation
      in the generation of peroxisome proliferator-activated receptor alpha agonists.

PMID- 11956199
TI  - Synphilin-1 is developmentally localized to synaptic terminals, and its
      association with synaptic vesicles is modulated by alpha-synuclein.
AB  - Alpha-synuclein is the major component of Lewy bodies in patients with
      Parkinson's disease, and mutations in the alpha-synuclein gene are responsible
      for some familial forms of the disease. alpha-Synuclein is enriched in the
      presynapse, but its synaptic targets are unknown. Synphilin-1 associates in vivo
      with alpha-synuclein promoting the formation of intracellular inclusions.
      Additionally synphilin-1 has been found to be an intrinsic component of Lewy
      bodies in patients with Parkinson's disease. To understand the role of synphilin
      1 in Parkinson's disease, we sought to define its localization and function in
      the brain. We now report that, like alpha-synuclein, synphilin-1 was enriched in
      neurons. In young rats, synphilin-1 was prominent in neuronal cell bodies but
      gradually migrated to neuropil during development. Immunoelectron microscopy of
      adult rat cerebral cortex demonstrated that synphilin-1 was highly enriched in
      presynaptic nerve terminals. Synphilin-1 co-immunoprecipitated with synaptic
      vesicles, indicating a strong association with these structures. In vitro binding
      experiments demonstrated that the N terminus of synphilin-1 robustly associated
      with synaptic vesicles and that this association was resistant to high salt
      washing but was abolished by inclusion of alpha-synuclein in the incubation
      medium. Our data indicated that synphilin-1 is a synaptic partner of alpha
      synuclein, and it may mediate synaptic roles attributed to alpha-synuclein.

PMID- 11956200
TI  - The C66W mutation in the deafness dystonia peptide 1 (DDP1) affects the formation
      of functional DDP1.TIM13 complexes in the mitochondrial intermembrane space.
AB  - Mohr-Tranebjaerg syndrome is a progressive, neurodegenerative disorder caused by
      loss-of-function mutations in the DDP1/TIMM8A gene. DDP1 belongs to a family of
      evolutionary conserved proteins that are organized in hetero-oligomeric complexes
      in the mitochondrial intermembrane space. They mediate the import and insertion
      of hydrophobic membrane proteins into the mitochondrial inner membrane. All of
      them share a conserved Cys(4) metal binding site proposed to be required for the
      formation of zinc fingers. So far, the only missense mutation known to cause a
      full-blown clinical phenotype is a C66W exchange directly affecting this Cys(4)
      motif. Here, we show that the mutant human protein is efficiently imported into
      mitochondria and sorted into the intermembrane space. In contrast to wild-type
      DDP1, it does not complement the function of its yeast homologue Tim8. The C66W
      mutation impairs binding of Zn(2+) ions via the Cys(4) motif. As a consequence,
      the mutated DDP1 is incorrectly folded and loses its ability to assemble into a
      hetero-hexameric 70-kDa complex with its cognate partner protein human Tim13.
      Thus, an assembly defect of DDP1 is the molecular basis of Mohr-Tranebjaerg
      syndrome in patients carrying the C66W mutation.

PMID- 11956201
TI  - The nucleolar localization domain of the catalytic subunit of human telomerase.
AB  - Telomerase is the enzyme essential to complete the replication of the terminal
      DNA of most eukaryotic chromosomes. In humans, this enzyme is composed of the
      telomerase reverse transcriptase (hTERT) and telomerase RNA (hTR) subunits. hTR
      has been found in the nucleolus, a site of assembly of ribosomes as well as other
      ribonucleoproteins (RNPs). We therefore tested whether the hTERT component is
      also found in the nucleolus, where it could complex with the hTR RNA to form a
      functional enzyme. We report here that hTERT does indeed localize to the
      nucleolus, and we mapped the domain responsible for this localization to the hTR
      binding region of the protein by deletion analysis. Substitution mutations in two
      of the three conserved hTR-binding domains in this nucleolar localization domain
      (NoLD) abolished nucleolar localization. However, another mutation that impeded
      hTR binding did not alter this subcellular localization. Additionally, wild type
      hTERT was detected in the nucleolus of cells that failed to express hTR. Taken
      together, we propose that the nucleolar localization of hTERT involves more than
      just the association with the hTR subunit. Furthermore, the coincidental
      targeting of both the hTR and hTERT subunits to the nucleolus supports the
      premise that the assembly of telomerase occurs in the nucleolus.

PMID- 11956202
TI  - Interchangeable enzyme modules. Functional replacement of the essential linker of
      the biotinylated subunit of acetyl-CoA carboxylase with a linker from the
      lipoylated subunit of pyruvate dehydrogenase.
AB  - Biotin carboxyl carrier protein (BCCP) is the small biotinylated subunit of
      Escherichia coli acetyl-CoA carboxylase, the enzyme that catalyzes the first
      committed step of fatty acid synthesis. E. coli BCCP is a member of a large
      family of protein domains modified by covalent attachment of biotin. In most
      biotinylated proteins, the biotin moiety is attached to a lysine residue located
      about 35 residues from the carboxyl terminus of the protein, which lies in the
      center of a strongly conserved sequence that forms a tightly folded anti-parallel
      beta-barrel structure. Located upstream of the conserved biotinoyl domain
      sequence are proline/alanine-rich sequences of varying lengths, which have been
      proposed to act as flexible linkers. In E. coli BCCP, this putative linker
      extends for about 42 residues with over half of the residues being proline or
      alanine. I report that deletion of the 30 linker residues located adjacent to the
      biotinoyl domain resulted in a BCCP species that was defective in function in
      vivo, although it was efficiently biotinylated. Expression of this BCCP species
      failed to restore normal growth and fatty acid synthesis to a temperature
      sensitive E. coli strain that lacks BCCP when grown at nonpermissive
      temperatures. In contrast, replacement of the deleted BCCP linker with a linker
      derived from E. coli pyruvate dehydrogenase gave a chimeric BCCP species that had
      normal in vivo function. Expression of BCCPs having deletions of various segments
      of the linker region of the chimeric protein showed that some deletions of up to
      24 residues had significant or full biological activity, whereas others had very
      weak or no activity. The inactive deletion proteins all lacked an APAAAAA
      sequence located adjacent to the tightly folded biotinyl domain, whereas
      deletions that removed only upstream linker sequences remained active. Deletions
      within the linker of the wild type BCCP protein also showed that the residues
      adjacent to the tightly folded domain play an essential role in protein function,
      although in this case some proteins with deletions within this region retained
      activity. Retention of activity was due to fusion of the domain to upstream
      sequences. These data provide new evidence for the functional and structural
      similarities of biotinylated and lipoylated proteins and strongly support a
      common evolutionary origin of these enzyme subunits.

PMID- 11956203
TI  - The mechanism of 1,25-dihydroxyvitamin D(3) autoregulation in keratinocytes.
AB  - The synthesis of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) from its precursor,
      25-dihydroxyvitamin D(3) (25(OH)D(3)), is catalyzed by the mitochondrial
      cytochrome P450 enzyme 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha
      hydroxylase). It has been generally assumed that 1,25(OH)(2)D(3) inhibits the
      activity of this enzyme by regulating its expression at the genomic level. We
      confirmed that 1,25(OH)(2)D(3) reduced the apparent conversion of 25(OH)D(3) to
      1,25(OH)(2)D(3) while stimulating the conversion of 1,25(OH)(2)D(3) and
      25(OH)D(3) to 1,24,25(OH)(3)D(3) and 24,25(OH)(2)D(3), respectively. However,
      1,25(OH)(2)D(3) failed to reduce the abundance of its mRNA or its encoded protein
      in human keratinocytes. Instead, when catabolism of 1,25(OH)(2)D(3) was blocked
      with a specific inhibitor of the 25-hydroxyvitamin D(3)-24-hydroxylase (24
      hydroxylase) all apparent inhibition of 1alpha-hydroxylase activity by
      1,25(OH)(2)D(3) was reversed. Thus, the apparent reduction in 1alpha-hydroxylase
      activity induced by 1,25(OH)(2)D(3) is due to increased catabolism of both
      substrate and product by the 24-hydroxylase. We believe this to be a unique
      mechanism for autoregulation of steroid hormone synthesis.

PMID- 11956204
TI  - Transcriptional effects of chronic Akt activation in the heart.
AB  - Akt activation reduces cardiomyocyte death and induces cardiac hypertrophy. To
      help identify effector mechanisms, gene expression profiles in hearts from
      transgenic mice with cardiac-specific expression of activated Akt (myr-Akt) were
      compared with littermate controls. 40 genes were identified as differentially
      expressed. Quantitative reverse transcription-PCR confirmed qualitative results
      of transcript profiling for 9 of 10 genes examined, however, there were notable
      quantitative discrepancies between the quantitative reverse transcription-PCR and
      microarray data sets. Interestingly Akt induced significant up-regulation of
      insulin-like growth factor-binding protein-5 (IGFBP-5), which could contribute to
      its anti-apoptotic effects in the heart. In addition, Akt-mediated down
      regulation of peroxisome proliferator-activated receptor (PPAR) gamma coactivator
      1 (PGC-1) and PPAR-alpha may shift myocytes toward glycolytic metabolism shown to
      preserve cardiomyocyte function and survival during transient ischemia. IGFBP-5
      transcripts also increased after adenoviral gene transfer of myr-Akt to cultured
      cardiomyocytes, suggesting that this represents a direct effect of Akt
      activation. In contrast, substantial induction of growth differentiation factor-8
      (GDF-8), a highly conserved inhibitor of skeletal muscle growth, was observed in
      transgenic hearts but not after acute Akt activation in vitro, suggesting that
      GDF-8 induction may represent a secondary effect perhaps related to the cardiac
      hypertrophy seen in these mice. Thus, microarray analysis reveals previously
      unappreciated Akt regulation of genes that could contribute to the effects of Akt
      on cardiomyocyte survival, metabolism, and growth.

PMID- 11956205
TI  - Expression of ectolipid phosphate phosphohydrolases in 3T3F442A preadipocytes and
      adipocytes. Involvement in the control of lysophosphatidic acid production.
AB  - Because of its production by adipocytes and its ability to increase preadipocyte
      proliferation, lysophosphatidic acid (LPA) could participate in the paracrine
      control of adipose tissue development. The aim of the present study was to
      determine which enzyme activities are involved in exogenous LPA hydrolysis by
      preadipocytes and adipocytes. Using a quantitative method, we observed that
      extracellular LPA rapidly disappeared from the culture medium of 3T3F442A
      preadipocytes. This disappearance was strongly slowed down in the presence of the
      phosphatase inhibitors, sodium vanadate and sodium pervanadate. By using
      [(33)P]LPA on intact 3T3F442A preadipocytes, we found that 90% of LPA hydrolysis
      resulted from LPA phosphatase activity biochemically related to previously
      described ectolipid phosphate phosphohydrolases (LPPs). Quantitative real time
      reverse transcriptase-PCR revealed that 3T3F442A preadipocytes expressed mRNAs of
      three known Lpp gene subtypes (1, 2, and 3), with a predominant expression of
      Lpp1 and Lpp3. Differentiation of 3T3F442A preadipocytes into adipocytes led to
      an 80% reduction in ecto-LPA phosphatase activity, with a concomitant down
      regulation in Lpp1, Lpp2, and Lpp3 mRNA expression. Despite this regulation,
      treatment of 3T3F442A adipocytes with sodium vanadate increased LPA production in
      the culture medium, suggesting the involvement of ecto-LPA phosphatase activity
      in the control of extracellular production of LPA by adipocytes. In conclusion,
      these data demonstrate that hydrolysis of extracellular LPA by preadipocytes and
      adipocytes mainly results from a dephosphorylation activity. This activity (i)
      occurs at the extracellular face of cell membrane, (ii) exhibits biochemical
      characteristics similar to those of the LPP, (iii) is negatively regulated during
      adipocyte differentiation, and (iv) plays an important role in the control of
      extracellular LPA production by adipocytes. Ecto-LPA phosphatase activity
      represents a potential target to control adipose tissue development.

PMID- 11956206
TI  - Ceramide kinase, a novel lipid kinase. Molecular cloning and functional
      characterization.
AB  - Ceramide-1-phosphate is a sphingolipid metabolite that has been implicated in
      membrane fusion of brain synaptic vesicles and neutrophil phagolysosome
      formation. Ceramide-1-phosphate can be produced by ATP-dependent ceramide kinase
      activity, although little is known of this enzyme because it has not yet been
      highly purified or cloned. Based on sequence homology to sphingosine kinase type
      1, we have now cloned a related lipid kinase, human ceramide kinase (hCERK).
      hCERK encodes a protein of 537 amino acids that has a catalytic region with a
      high degree of similarity to the diacylglycerol kinase catalytic domain. hCERK
      also has a putative N-myristoylation site on its NH(2) terminus followed by a
      pleckstrin homology domain. Membrane but not cytosolic fractions from HEK293
      cells transiently transfected with a hCERK expression vector readily
      phosphorylated ceramide but not sphingosine or other sphingoid bases,
      diacylglycerol or phosphatidylinositol. This activity was clearly distinguished
      from those of bacterial or human diacylglycerol kinases. With natural ceramide as
      a substrate, the enzyme had a pH optimum of 6.0-7.5 and showed Michaelis-Menten
      kinetics, with K(m) values of 187 and 32 microm for ceramide and ATP,
      respectively. Northern blot analysis revealed that hCERK mRNA expression was high
      in the brain, heart, skeletal muscle, kidney, and liver. A BLAST search analysis
      using the hCERK sequence revealed that putative ceramide kinases (CERKs) exist
      widely in diverse multicellular organisms including plants, nematodes, insects,
      and vertebrates. Phylogenetic analysis revealed that CERKs are a new class of
      lipid kinases that are clearly distinct from sphingosine and diacylglycerol
      kinases. Cloning of CERK should provide new molecular tools to investigate the
      physiological functions of ceramide-1-phosphate.

PMID- 11956207
TI  - Nuclear factor of activated T cells is a driving force for preferential
      productive HIV-1 infection of CD45RO-expressing CD4+ T cells.
AB  - Human immunodeficiency virus type-1 (HIV-1) preferentially replicates in CD4
      expressing T cells bearing a "memory" (CD45RO+) rather than a "naive"
      (CD45RA+/CD62L+) phenotype. Yet the basis for the higher susceptibility of these
      cells to HIV-1 infection remains unclear. Because the nature of the CD45 isoform
      itself can affect biochemical events in T cells, we set out to determine whether
      these isoforms could differently modulate HIV-1 long terminal repeat (LTR)
      activity and thereby replication. Through the use of CD4+ Jurkat T cells
      specifically expressing distinct CD45 isoforms (i.e. CD45RABC or CD45RO), we
      demonstrated that a difference in CD45 isoform expression conferred preferential
      replication of HIV-1 to CD45RO-expressing T cell clones following a physiological
      CD3/CD28 stimulation. Closer analysis indicated that higher HIV-1 LTR activation
      levels were consistently observed in CD45RO-positive cells, which was paralleled
      by more pronounced nuclear factor of activated T cells (NFAT) activation in these
      same cells. Specific involvement of NFAT1 was revealed in studied Jurkat clones
      by mobility shift analyses. In addition, preferential activation of the LTR and
      viral replication in CD45RO T cells was FK506- and cyclosporin A-sensitive. These
      results underscore the importance of NFAT in HIV-1 regulation and for the first
      time identify the role of the CD45 isoform in limiting productive HIV-1
      replication to the human CD4 memory T cell subset.

PMID- 11956208
TI  - The novel human DNA helicase hFBH1 is an F-box protein.
AB  - We have identified a novel DNA helicase in humans that belongs to members of the
      superfamily I helicase and found that it contains a well conserved F-box motif at
      its N terminus. We have named the enzyme hFBH1 (human F-box DNA helicase 1).
      Recombinant hFBH1, containing glutathione S-transferase at the N terminus, was
      expressed in Sf9 cells and purified. In this report, we show that hFBH1 exhibited
      DNA-dependent ATPase and DNA unwinding activities that displace duplex DNA in the
      3' to 5' direction. The hFBH1 enzyme interacted with human SKP1 and formed an SCF
      (SKP1/Cullin/F-box) complex together with human Cullin and ROC1. In addition, the
      SCF complex containing hFBH1 as an F-box protein displayed ubiquitin ligase
      activity. We demonstrate that hFBH1 is the first F-box protein that possesses
      intrinsic enzyme activity. The potential role of the F-box motif and the helicase
      activity of the enzyme are discussed with regard to regulation of DNA metabolism.

PMID- 11956209
TI  - Complementation of pulmonary abnormalities in SP-D(-/-) mice with an SP
      D/conglutinin fusion protein.
AB  - Surfactant protein D (SP-D) and serum conglutinin are closely related members of
      the collectin family of host defense lectins. Although normally synthesized at
      different anatomic sites, both proteins participate in the innate immune response
      to microbial challenge. To discern the roles of specific domains in the function
      of SP-D in vivo, a fusion protein (SP-D/Cong(neck+CRD)) consisting of the NH(2)
      terminal and collagenous domains of rat SP-D (rSP-D) and the neck and
      carbohydrate recognition domains (CRDs) of bovine conglutinin (Cong) was
      expressed in the respiratory epithelium of SP-D gene-targeted (SP-D(-/-)) mice.
      While SP-D/Cong(neck+CRD) fusion protein did not affect lung morphology and
      surfactant phospholipid levels in the lungs of wild type mice, the chimeric
      protein substantially corrected the increased lung phospholipids in SP-D(-/-)
      mice. The SP-D/Cong(neck+CRD) fusion protein also completely corrected defects in
      influenza A clearance and inhibited the exaggerated inflammatory response that
      occurs following viral infection. However, the chimeric protein did not
      ameliorate the ongoing lung inflammation, enhanced metalloproteinase expression,
      and alveolar destruction that characterize this model of SP-D deficiency. By
      contrast, a single arm mutant (RrSP-D(Ser15,20)) partially restored antiviral
      activity but otherwise failed to rescue the deficient phenotype. Our findings
      directly implicate the CRDs of both SP-D and conglutinin in host defense in vivo.
      Our findings also strongly suggest that the molecular mechanisms underlying
      impaired pulmonary host defense and abnormal lipid metabolism are distinct from
      those that promote ongoing inflammation and the development of emphysema.

PMID- 11956210
TI  - Tat acetyl-acceptor lysines are important for human immunodeficiency virus type-1
      replication.
AB  - The human immunodeficiency virus type-1 trans-activator Tat is a transcription
      factor that activates the HIV-1 promoter through binding to the trans-activation
      responsive region (TAR) localized at the 5'-end of all viral transcripts. We and
      others have recently shown that Tat is directly acetylated at lysine 28, within
      the activation domain, and lysine 50, in the TAR RNA binding domain, by Tat
      associated histone acetyltransferases p300, p300/CBP-associating factor, and
      hGCN5. Here, we show that mutation of acetyl-acceptor lysines to arginine or
      glutamine affects virus replication. Interestingly, mutation of lysine 28 and
      lysine 50 differentially affected Tat trans-activation of integrated versus
      nonintegrated long terminal repeat. Our results highlight the importance of
      lysine 28 and lysine 50 of Tat in virus replication and Tat-mediated trans
      activation.

PMID- 11956211
TI  - Protein kinase C epsilon-dependent regulation of cystic fibrosis transmembrane
      regulator involves binding to a receptor for activated C kinase (RACK1) and RACK1
      binding to Na+/H+ exchange regulatory factor.
AB  - Protein kinase C (PKC) regulation of cystic fibrosis transmembrane regulator
      (CFTR) chloride function has been demonstrated in several cell lines, including
      Calu-3 cells that express native, wild-type CFTR. We demonstrated previously that
      PKC epsilon was required for cAMP-dependent CFTR function. The goal of this study
      was to determine whether PKC epsilon interacts directly with CFTR. Using overlay
      assay, immunoprecipitation, pulldown and binding assays, we show that PKC epsilon
      does not bind to CFTR, but does bind to a receptor for activated C kinase
      (RACK1), a 37-kDa scaffold protein, and that RACK1 binds to Na(+)/H(+) exchange
      regulatory factor (NHERF1), a binding partner of CFTR. In vitro binding assays
      demonstrate dose-dependent binding of PKC epsilon to RACK1 which is inhibited by
      an 8-amino acid peptide based on the sequence of the sixth Trp-Asp repeat in
      RACK1 or by an 8-amino acid sequence in the V1 region of PKC epsilon, epsilon V1
      2. A 4-amino acid sequence INAL (70-73) expressed in CFTR shares 50% homology to
      the RACK1 inhibitory peptide, but it does not bind PKC epsilon. NHERF1 and RACK1
      bind in a dose-dependent manner. Immunofluorescence and confocal microscopy of
      RACK1 and CFTR revealed colocalization of the proteins to the apical and lateral
      regions of Calu-3 cells. The results indicate the RACK1 binds PKC epsilon and
      NHERF1, thus serving as a scaffold protein to anchor the enzyme in proximity to
      CFTR.

PMID- 11956212
TI  - Three novel sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 3 isoforms.
      Expression, regulation, and function of the membranes of the SERCA3 family.
AB  - Sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) pump Ca2+ into the endoplasmic
      reticulum. Recently, three human SERCA3 (h3a-c) proteins and a previously unknown
      rat SERCA3 (r3b/c) mRNA have been described. Here, we (i) document two novel
      human SERCA3 splice variants h3d and h3e, (ii) provide data for the expression
      and mechanisms regulating the expression of all known SERCA3 variants (r3a,
      r3b/c, and h3a-e), and (iii) show functional characteristics of the SERCA3
      isoforms. h3d and h3e are issued from the insertion of an additional penultimate
      exon 22 resulting in different carboxyl termini for these variants. Distinct
      distribution patterns of the SERCA3 gene products were observed in a series of
      cell lines of hematopoietic, epithelial, embryonic origin, and several cancerous
      types, as well as in panels of rat and human tissues. Hypertension and protein
      kinase C, calcineurin, or retinoic acid receptor signaling pathways were found to
      differently control rat and human splice variant expression, respectively. Stable
      overexpression of each variant was performed in human embryonic kidney 293 cells,
      and the SERCA3 isoforms were fully characterized. All SERCA3 isoforms were found
      to pump Ca2+ with similar affinities. However, they modulated the cytosolic Ca2+
      concentration ([Ca2+]c) and the endoplasmic reticulum Ca2+ content ([Ca2+]er) in
      different manners. A newly generated polyclonal antibody and a pan-SERCA3
      antibody proved the endogenous expression of the three novel SERCA3 proteins,
      h3d, h3e, and r3b/c. All these data suggest that the SERCA3 gene products have a
      more widespread role in cellular Ca2+ signaling than previously appreciated.

PMID- 11956213
TI  - In Saccharomyces cerevisiae, the inositol polyphosphate kinase activity of Kcs1p
      is required for resistance to salt stress, cell wall integrity, and vacuolar
      morphogenesis.
AB  - A problem for inositol signaling is to understand the significance of the kinases
      that convert inositol hexakisphosphate to diphosphoinositol polyphosphates. This
      kinase activity is catalyzed by Kcs1p in the yeast Saccharomyces cerevisiae. A
      kcs1Delta yeast strain that was transformed with a specifically "kinase-dead"
      kcs1p mutant did not synthesize diphosphoinositol polyphosphates, and the cells
      contained a fragmented vacuolar compartment. Biogenesis of the yeast vacuole also
      required another functional domain in Kcs1p, which contains two leucine heptad
      repeats. The kinase activity of Kcs1p was also found to sustain cell growth and
      integrity of the cell wall and to promote adaptive responses to salt stress.
      Thus, the synthesis of diphosphoinositol polyphosphates has wide ranging
      physiological significance. Furthermore, we showed that these phenotypic
      responses to Kcs1p deletion also arise when synthesis of precursor material for
      the diphosphoinositol polyphosphates is blocked in arg82Delta cells. This
      metabolic block was partially bypassed, and the phenotype was partially rescued,
      when Kcs1p was overexpressed in the arg82Delta cells. This was due, in part, to
      the ability of Kcs1p to phosphorylate a wider range of substrates than previously
      appreciated. Our results show that diphosphoinositol polyphosphate synthase
      activity is essential for biogenesis of the yeast vacuole and the cell's
      responses to certain environmental stresses.

PMID- 11956214
TI  - A 3'-terminal minihelix in the precursor of human spliceosomal U2 small nuclear
      RNA.
AB  - U2 RNA is one of five small nuclear RNAs that participate in the majority of mRNA
      splicing. In addition to its role in mRNA splicing, the biosynthesis of U2 RNA
      and three of the other spliceosomal RNAs is itself an intriguing process
      involving nuclear export followed by 5'-cap hypermethylation, assembly with
      specific proteins, 3' end processing, and then nuclear import. Previous work has
      identified sequences near the 3' end of pre-U2 RNA that are required for accurate
      and efficient processing. In this study, we have investigated the structural
      basis of U2 RNA 3' end processing by chemical and enzymatic probing methods. Our
      results demonstrate that the 3' end of pre-U2 RNA is a minihelix with an
      estimated stabilization free energy of -6.9 kcal/mol. Parallel RNA structure
      mapping experiments with mutant pre-U2 RNAs revealed that the presence of this 3'
      minihelix is itself not required for in vitro 3'-processing of pre-U2 RNA, in
      support of earlier studies implicating internal regions of pre-U2 RNA. Other
      considerations raise the possibility that this distinctive structural motif at
      the 3' end of pre-U2 RNA plays a role in the cleavage of the precursor from its
      longer primary transcript or in its nucleocytoplasmic traffic.

PMID- 11956215
TI  - Roles of catalytic domain residues in interfacial binding and activation of group
      IV cytosolic phospholipase A2.
AB  - Group IV cytosolic phospholipase A(2) (cPLA(2)) has been shown to play a critical
      role in eicosanoid biosynthesis. cPLA(2) is composed of the C2 domain that
      mediates the Ca(2+)-dependent interfacial binding of protein and the catalytic
      domain. To elucidate the mechanism of interfacial activation of cPLA(2), we
      measured the effects of mutations of selected ionic and hydrophobic residues in
      the catalytic domain on the enzyme activity and the membrane binding of cPLA(2).
      Mutations of anionic residues located on (Glu(419) and Glu(420)) or near
      (Asp(436), Asp(438), Asp(439), and Asp(440)) the active site lid enhanced the
      affinity for cPLA(2) for anionic membranes, implying that the electrostatic
      repulsion between these residues and the anionic membrane surface might trigger
      the opening of the active site. This notion is further supported by a biphasic
      dependence of cPLA(2) activity on the anionic lipid composition of the vesicles.
      Mutations of a cluster of cationic residues (Lys(541), Lys(543), Lys(544), and
      Arg(488)), while significantly enhancing the activity of enzyme, abrogated the
      specific activation effect by phosphatidylinositol 4,5-bisphosphate
      (PtdIns(4,5)P(2)). These data, in conjunction with cell activity of cPLA(2) and
      mutants transfected into HEK293 cells, suggest that the cationic residues form a
      specific binding site for PtdIns(4,5)P(2) and that the specific PtdIns(4,5)P(2)
      binding is involved in cellular activation of cPLA(2). Also, three hydrophobic
      residues at the rim of the active site (Ile(399), Leu(400), and Leu(552)) were
      shown to partially penetrate the membrane, thereby promoting membrane binding and
      activation of cPLA(2). Based on these results, we propose an interfacial
      activation mechanism for cPLA(2) which involves the removal of the active site
      lid by nonspecific electrostatic repulsion, the interdomain hinge movement
      induced by specific PtdIns(4,5)P(2) binding, and the partial membrane penetration
      by catalytic domain hydrophobic residues.

PMID- 11956216
TI  - Importance of the N-terminal region of the phage GA-1 single-stranded DNA-binding
      protein for its self-interaction ability and functionality.
AB  - The single-stranded DNA-binding protein (SSB) of phage GA-1 displays higher
      efficiency than the SSBs of the related phages phi 29 and Nf. In this work, the
      self-interaction ability of GA-1 SSB has been analyzed by visualization of the
      purified protein by electron microscopy, glycerol gradient sedimentation, and in
      vivo cross-linking of bacterial cultures infected with phage GA-1. GA-1 SSB
      contains an insert at its N-terminal region that is not present in the SSBs of
      phi 29 and Nf. Three deletion mutant proteins have been characterized, Delta N19,
      Delta N26, and Delta N33, which lack the 19, 26 or 33 amino acids, respectively,
      that follow the initial methionine of GA-1 SSB. Mutant protein Delta N19 retains
      the structural and functional behavior of GA-1 SSB, whereas mutant proteins Delta
      N26 and Delta N33 no longer stimulate viral DNA replication or display helix
      destabilizing activity. Analysis of the mutant proteins by ultracentrifugation in
      glycerol gradients and electron microscopy indicates that deletion of 26 or 33
      but not of 19 amino acids of the N-terminal region of GA-1 SSB results in the
      loss of the oligomerization ability of this protein. Our data support the
      importance of the N-terminal region of GA-1 SSB for the differential self
      interaction ability and functional behavior of this protein.

PMID- 11956217
TI  - RYK, a catalytically inactive receptor tyrosine kinase, associates with EphB2 and
      EphB3 but does not interact with AF-6.
AB  - RYK is an atypical orphan receptor tyrosine kinase that lacks detectable kinase
      activity. Nevertheless, using a chimeric receptor approach, we previously found
      that RYK can signal via the mitogen-activated protein kinase pathway. Recently,
      it has been shown that murine Ryk can bind to and be phosphorylated by the ephrin
      receptors EphB2 and EphB3. In this study, we show that human RYK associates with
      EphB2 and EphB3 but is not phosphorylated by them. This association requires both
      the extracellular and cytoplasmic domains of RYK and is not dependent on
      activation of the Eph receptors. It was also previously shown that AF-6 (afadin),
      a PDZ domain-containing protein, associates with murine Ryk. We show here that AF
      6 does not bind to human RYK in vitro or in vivo. This suggests that there are
      significant functional differences between human and murine RYK. Further studies
      are required to determine whether RYK modulates the signaling of EphB2 and EphB3.

PMID- 11956218
TI  - RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein with
      calcium- and diacylglycerol-binding motifs. Identification of defective variants
      of this signaling protein in asthma, mastocytosis, and mast cell leukemia
      patients and demonstration of the importance of RasGRP4 in mast cell development
      and function.
AB  - A cDNA was isolated from interleukin 3-developed, mouse bone marrow-derived mast
      cells (MCs) that contained an insert (designated mRasGRP4) that had not been
      identified in any species at the gene, mRNA, or protein level. By using a
      homology-based cloning approach, the approximately 2.6-kb hRasGRP4 transcript was
      also isolated from the mononuclear progenitors residing in the peripheral blood
      of normal individuals. This transcript information was then used to locate the
      RasGRP4 gene in the mouse and human genomes, to deduce its exon/intron
      organization, and then to identify 10 single nucleotide polymorphisms in the
      human gene that result in 5 amino acid differences. The >15-kb hRasGRP4 gene
      consists of 18 exons and resides on a region of chromosome 19q13.1 that had not
      been sequenced by the Human Genome Project. Human and mouse MCs and their
      progenitors selectively express RasGRP4, and this new intracellular protein
      contains all of the domains present in the RasGRP family of guanine nucleotide
      exchange factors even though it is <50% identical to its closest homolog.
      Recombinant RasGRP4 can activate H-Ras in a cation-dependent manner. Transfection
      experiments also suggest that RasGRP4 is a diacylglycerol/phorbol ester receptor.
      Transcript analysis of an asthma patient, a mastocytosis patient, and the HMC-1
      cell line derived from a MC leukemia patient revealed the presence of substantial
      amounts of non-functional forms of hRasGRP4 due to an inability to remove intron
      5 in the precursor transcript. Because only abnormal forms of hRasGRP4 were
      identified in the HMC-1 cell line, this immature MC progenitor was used to
      address the function of RasGRP4 in MCs. HMC-1 leukemia cells differentiated and
      underwent granule maturation when induced to express a normal form of RasGRP4.
      Thus, RasGRP4 plays an important role in the final stages of MC development.

PMID- 11956219
TI  - Fep1, an iron sensor regulating iron transporter gene expression in
      Schizosaccharomyces pombe.
AB  - Schizosaccharomyces pombe cells acquire iron under high affinity conditions
      through the action of a cell surface ferric reductase encoded by the frp1(+) gene
      and a two-component iron-transporting complex encoded by the fip1(+) and fio1(+)
      genes. When cells are grown in the presence of iron, transcription of all three
      genes is blocked. A conserved regulatory element, 5'-(A/T)GATAA-3', located
      upstream of the frp1(+), fip1(+), and fio1(+) genes, is necessary for iron
      repression. We have cloned a novel gene, termed fep1(+), which encodes an iron
      sensing transcription factor. Binding studies reveal that the putative DNA
      binding domain of Fep1 expressed as a fusion protein in Escherichia coli
      specifically interacts with the 5'-(A/T)GATAA-3' sequence in an iron-dependent
      manner. In a fep1 Delta mutant strain, the fio1(+) gene is highly expressed and
      is unregulated by iron. Furthermore, the fep1 Delta mutation increases activity
      of the cell surface iron reductase and renders cells hypersensitive to the iron
      dependent free radical generator phleomycin. Mutations in the transcriptional co
      repressors tup11(+) and tup12(+) are phenocopies to fep1(+). Indeed, strains with
      both tup11 Delta and tup12 Delta deletions fail to sense iron. This suggests that
      in the presence of iron and Fep1, the Tup11 and Tup12 proteins may act as co
      repressors for down-regulation of genes encoding components of the reductive iron
      transport machinery.

PMID- 11956220
TI  - Activation of human monoamine oxidase B gene expression by a protein kinase C
      MAPK signal transduction pathway involves c-Jun and Egr-1.
AB  - Monoamine oxidases (MAO) A and B deaminate a number of biogenic amines. Aberrant
      expression of MAO is implicated in several psychiatric and neurogenerative
      disorders. In this study, we have shown that phorbol 12-myristate 13-acetate
      (PMA) increases human MAO B, but not MAO A, gene expression. The sequence between
      -246 and -225 bp consists of overlapping binding sites (Sp1/Egr-1/Sp1) that are
      recognized by Sp1, Sp3, and PMA-inducible Egr-1 is essential for PMA activation.
      PMA transiently increases egr-1 and c-jun gene expression. Mutation studies show
      that Egr-1 and c-Jun transactivate the MAO B promoter and increase endogenous MAO
      B transcripts via the Sp1/Egr-1/Sp1 overlapping binding sites. Sp3 inhibits Sp1
      and Egr-1 activation of MAO B gene expression. c-fos gene expression was
      increased by PMA but not involved in MAO B gene transcription. Furthermore,
      protein kinase C inhibitor blocks the PMA-dependent activation of MAO B. Co
      transfection of the MAO B promoter with dominant negative forms of Ras, Raf-1,
      MEKK1, MEK1, MEK3, MEK7, ERK2, JNK1, and p38/RK inhibit the PMA-dependent
      activation of the MAO B promoter. These results indicate that MAO B expression is
      selectively induced by the activation of protein kinase C and MAPK signaling
      pathway and that c-Jun and Egr-1 appear to be the ultimate targets of this
      regulation.

PMID- 11956221
TI  - H+-pyrophosphatase of Rhodospirillum rubrum. High yield expression in Escherichia
      coli and identification of the Cys residues responsible for inactivation my
      mersalyl.
AB  - H(+)-translocating pyrophosphatase (H(+)-PPase) of the photosynthetic bacterium
      Rhodospirillum rubrum was expressed in Escherichia coli C43(DE3) cells.
      Recombinant H(+)-PPase was observed in inner membrane vesicles, where it
      catalyzed both PP(i) hydrolysis coupled with H(+) transport into the vesicles and
      PP(i) synthesis. The hydrolytic activity of H(+)-PPase in E. coli vesicles was
      eight times greater than that in R. rubrum chromatophores but exhibited similar
      sensitivity to the H(+)-PPase inhibitor, aminomethylenediphosphonate, and
      insensitivity to the soluble PPase inhibitor, fluoride. Using this expression
      system, we showed that substitution of Cys(185), Cys(222), or Cys(573) with
      aliphatic residues had no effect on the activity of H(+)-PPase but decreased its
      sensitivity to the sulfhydryl modifying reagent, mersalyl. H(+)-PPase lacking all
      three Cys residues was completely resistant to the effects of mersalyl. Mg(2+)
      and MgPP(i) protected Cys(185) and Cys(573) from modification by this agent but
      not Cys(222). Phylogenetic analyses of 23 nonredundant H(+)-PPase sequences led
      to classification into two subfamilies. One subfamily invariably contains
      Cys(222) and includes all known K(+)-independent H(+)-PPases, whereas the other
      incorporates a conserved Cys(573) but lacks Cys(222) and includes all known K(+)
      dependent H(+)-PPases. These data suggest a specific link between the incidence
      of Cys at positions 222 and 573 and the K(+) dependence of H(+)-PPase.

PMID- 11956222
TI  - Identification of 14-3-3zeta as a protein kinase B/Akt substrate.
AB  - Protein kinase B/Akt (PKB/Akt) is a member of the ACG kinase family, which also
      includes protein kinase C, that phosphorylates a number of 14-3-3-binding
      proteins. 14-3-3 protein regulation of protein kinase C activity is modulated by
      14-3-3 phosphorylation. We examined the hypothesis that PKB/Akt interacts with
      and phosphorylates 14-3-3zeta, leading to modulation of dimerization. By
      glutathione S-transferase pull-down, Akt precipitated recombinant 14-3-3zeta and
      endogenous 14-3-3zeta from HEK293 cell lysates. Recombinant active PKB/Akt
      phosphorylated recombinant 14-3-3zeta in an in vitro kinase assay. Transfection
      of active PKB/Akt into HEK293 cells resulted in phosphorylation of 14-3-3zeta.
      Based on a motif search of 14-3-3zeta, a potential PKB/Akt phosphorylation site,
      Ser-58, was mutated to alanine. PKB/Akt was unable to phosphorylate this mutant
      protein. Incubation of 14-3-3zeta with recombinant active PKB/Akt resulted in
      phosphorylation of 45% of the protein, as determined by a pI shift on two
      dimensional electrophoresis, but 14-3-3zeta dimerization was not altered. These
      data indicate that PKB/Akt phosphorylates Ser-58 on 14-3-3zeta both in vitro and
      in intact cells. The functional relevance of this phosphorylation remains to be
      determined.

PMID- 11956223
TI  - Simple centromere, complex kinetochore: linking spindle microtubules and
      centromeric DNA in budding yeast.
AB  - Although the budding yeast centromere is extremely short (125 bp) compared to
      those of other eukaryotes, the kinetochore that assembles on this DNA displays a
      rich molecular complexity. Here, we describe recent advances in our understanding
      of kinetochore function in budding yeast and present a model describing the
      attachment that is formed between spindle microtubules and centromeric DNA. This
      analysis may provide general principles for kinetochore function and regulation.

PMID- 11956224
TI  - A twin arginine signal peptide and the pH gradient trigger reversible assembly of
      the thylakoid [Delta]pH/Tat translocase.
AB  - The thylakoid DeltapH-dependent/Tat pathway is a novel system with the remarkable
      ability to transport tightly folded precursor proteins using a transmembrane
      DeltapH as the sole energy source. Three known components of the transport
      machinery exist in two distinct subcomplexes. A cpTatC-Hcf106 complex serves as
      precursor receptor and a Tha4 complex is required after precursor recognition.
      Here we report that Tha4 assembles with cpTatC-Hcf106 during the translocation
      step. Interactions among components were examined by chemical cross-linking of
      intact thylakoids followed by immunoprecipitation and immunoblotting. cpTatC and
      Hcf106 were consistently associated under all conditions tested. In contrast,
      Tha4 was only associated with cpTatC and Hcf106 in the presence of a functional
      precursor and the DeltapH. Interestingly, a synthetic signal peptide could
      replace intact precursor in triggering assembly. The association of all three
      components was transient and dissipated upon the completion of protein
      translocation. Such an assembly-disassembly cycle could explain how the
      DeltapH/Tat system can assemble translocases to accommodate folded proteins of
      varied size. It also explains in part how the system can exist in the membrane
      without compromising its ion and proton permeability barrier.

PMID- 11956225
TI  - An inactive pool of GSK-3 at the leading edge of growth cones is implicated in
      Semaphorin 3A signaling.
AB  - Glycogen synthase kinase (GSK)-3 is a serine/threonine kinase that has been
      implicated in several aspects in embryonic development and several growth factor
      signaling cascades. We now report that an inactive phosphorylated pool of the
      enzyme colocalizes with F-actin in both neuronal and nonneuronal cells.
      Semaphorin 3A (Sema 3A), a molecule that inhibits axonal growth, activates GSK-3
      at the leading edge of neuronal growth cones and in Sema 3A-responsive human
      breast cancer cells, suggesting that GSK-3 activity might play a role in coupling
      Sema 3A signaling to changes in cell motility. We show that three different GSK-3
      antagonists (LiCl, SB-216763, and SB-415286) can inhibit the growth cone collapse
      response induced by Sema 3A. These studies reveal a novel compartmentalization of
      inactive GSK-3 in cells and demonstrate for the first time a requirement for GSK
      3 activity in the Sema 3A signal transduction pathway.

PMID- 11956226
TI  - Telomeres act autonomously in maize to organize the meiotic bouquet from a
      semipolarized chromosome orientation.
AB  - During meiosis, chromosomes undergo large-scale reorganization to allow pairing
      between homologues, which is necessary for recombination and segregation. In many
      organisms, pairing of homologous chromosomes is accompanied, and possibly
      facilitated, by the bouquet, the clustering of telomeres in a small region of the
      nuclear periphery. Taking advantage of the cytological accessibility of meiosis
      in maize, we have characterized the organization of centromeres and telomeres
      throughout meiotic prophase. Our results demonstrate that meiotic centromeres are
      polarized prior to the bouquet stage, but that this polarization does not
      contribute to bouquet formation. By examining telocentric and ring chromosomes,
      we have tested the cis-acting requirements for participation in the bouquet. We
      find that: (a) the healed ends of broken chromosomes, which contain telomere
      repeats, can enter the bouquet; (b) ring chromosomes enter the bouquet,
      indicating that terminal position on a chromosome is not necessary for telomere
      sequences to localize to the bouquet; and (c) beginning at zygotene, the behavior
      of telomeres is dominant over any centromere-mediated chromosome behavior. The
      results of this study indicate that specific chromosome regions are acted upon to
      determine the organization of meiotic chromosomes, enabling the bouquet to form
      despite large-scale changes in chromosome architecture.

PMID- 11956227
TI  - The utrophin actin-binding domain binds F-actin in two different modes:
      implications for the spectrin superfamily of proteins.
AB  - Utrophin, like its homologue dystrophin, forms a link between the actin
      cytoskeleton and the extracellular matrix. We have used a new method of image
      analysis to reconstruct actin filaments decorated with the actin-binding domain
      of utrophin, which contains two calponin homology domains. We find two different
      modes of binding, with either one or two calponin-homology (CH) domains bound per
      actin subunit, and these modes are also distinguishable by their very different
      effects on F-actin rigidity. Both modes involve an extended conformation of the
      CH domains, as predicted by a previous crystal structure. The separation of these
      two modes has been largely dependent upon the use of our new approach to
      reconstruction of helical filaments. When existing information about tropomyosin,
      myosin, actin-depolymerizing factor, and nebulin is considered, these results
      suggest that many actin-binding proteins may have multiple binding sites on F
      actin. The cell may use the modular CH domains found in the spectrin superfamily
      of actin-binding proteins to bind actin in manifold ways, allowing for complexity
      to arise from the interactions of a relatively few simple modules with actin.

PMID- 11956228
TI  - Translocation of PKC[theta] in T cells is mediated by a nonconventional, PI3-K-
      and Vav-dependent pathway, but does not absolutely require phospholipase C.
AB  - PKCtheta plays an essential role in activation of mature T cells via stimulation
      of AP-1 and NF-kappaB, and is known to selectively translocate to the
      immunological synapse in antigen-stimulated T cells. Recently, we reported that a
      Vav/Rac pathway which depends on actin cytoskeleton reorganization mediates
      selective recruitment of PKCtheta to the membrane or cytoskeleton and its
      catalytic activation by anti-CD3/CD28 costimulation. Because this pathway acted
      selectively on PKCtheta, we addressed here the question of whether the
      translocation and activation of PKCtheta in T cells is regulated by a unique
      pathway distinct from the conventional mechanism for PKC activation, i.e., PLC
      mediated production of DAG. Using three independent approaches, i.e., a selective
      PLC inhibitor, a PLCgamma1-deficient T cell line, or a dominant negative
      PLCgamma1 mutant, we demonstrate that CD3/CD28-induced membrane recruitment and
      COOH-terminal phosphorylation of PKCtheta are largely independent of PLC. In
      contrast, the same inhibitory strategies blocked the membrane translocation of
      PKCalpha. Membrane or lipid raft recruitment of PKCtheta (but not PKCalpha) was
      absent in T cells treated with phosphatidylinositol 3-kinase (PI3-K) inhibitors
      or in Vav-deficient T cells, and was enhanced by constitutively active PI3-K. 3
      phosphoinositide-dependent kinase-1 (PDK1) also upregulated the membrane
      translocation of PKCtheta;, but did not associate with it. These results provide
      evidence that a nonconventional PI3-K- and Vav-dependent pathway mediates the
      selective membrane recruitment and, possibly, activation of PKCtheta in T cells.

PMID- 11956229
TI  - Specific SHP-2 partitioning in raft domains triggers integrin-mediated signaling
      via Rho activation.
AB  - Cell signaling does not occur randomly over the cell surface, but is integrated
      within cholesterol-enriched membrane domains, termed rafts. By targeting SHP-2 to
      raft domains or to a non-raft plasma membrane fraction, we studied the functional
      role of rafts in signaling. Serum-depleted, nonattached cells expressing the raft
      SHP-2 form, but not non-raft SHP-2, display signaling events resembling those
      observed after fibronectin attachment, such as beta1 integrin clustering, 397Y
      FAK phosphorylation, and ERK activation, and also increases Rho-GTP levels.
      Expression of the dominant negative N19Rho abrogates raft-SHP-2-induced
      signaling, suggesting that Rho activation is a downstream event in SHP-2
      signaling. Expression of a catalytic inactive SHP-2 mutant abrogates the adhesion
      induced feedback inhibition of Rho activity, suggesting that SHP-2 contributes to
      adhesion-induced suppression of Rho activity. Because raft recruitment of SHP-2
      occurs physiologically after cell attachment, these results provide a mechanism
      by which SHP-2 may influence cell adhesion and migration by spatially regulating
      Rho activity.

PMID- 11956230
TI  - The GTP binding proteins Gem and Rad are negative regulators of the Rho-Rho
      kinase pathway.
AB  - The cytoskeletal changes that alter cellular morphogenesis and motility depend
      upon a complex interplay among molecules that regulate actin, myosin, and other
      cytoskeletal components. The Rho family of GTP binding proteins are important
      upstream mediators of cytoskeletal organization. Gem and Rad are members of
      another family of small GTP binding proteins (the Rad, Gem, and Kir family) for
      which biochemical functions have been mostly unknown. Here we show that Gem and
      Rad interface with the Rho pathway through association with the Rho effectors,
      Rho kinase (ROK) alpha and beta. Gem binds ROKbeta independently of RhoA in the
      ROKbeta coiled-coil region adjacent to the Rho binding domain. Expression of Gem
      inhibited ROKbeta-mediated phosphorylation of myosin light chain and myosin
      phosphatase, but not LIM kinase, suggesting that Gem acts by modifying the
      substrate specificity of ROKbeta. Gem or Rad expression led to cell flattening
      and neurite extension in N1E-115 neuroblastoma cells. In interference assays, Gem
      opposed ROKbeta- and Rad opposed ROKalpha-mediated cell rounding and neurite
      retraction. Gem did not oppose cell rounding initiated by ROKbeta containing a
      deletion of the Gem binding region, demonstrating that Gem binding to ROKbeta is
      required for the effects observed. In epithelial or fibroblastic cells, Gem or
      Rad expression resulted in stress fiber and focal adhesion disassembly. In
      addition, Gem reverted the anchorage-independent growth and invasiveness of Dbl
      transformed fibroblasts. These results identify physiological roles for Gem and
      Rad in cytoskeletal regulation mediated by ROK.

PMID- 11956232
TI  - Overexpression of the myelin proteolipid protein leads to accumulation of
      cholesterol and proteolipid protein in endosomes/lysosomes: implications for
      Pelizaeus-Merzbacher disease.
AB  - Duplications and overexpression of the proteolipid protein (PLP) gene are known
      to cause the dysmyelinating disorder Pelizaeus-Merzbacher disease (PMD). To
      understand the cellular response to overexpressed PLP in PMD, we have
      overexpressed PLP in BHK cells and primary cultures of oligodendrocytes with the
      Semliki Forest virus expression system. Overexpressed PLP was routed to late
      endosomes/lysosomes and caused a sequestration of cholesterol in these
      compartments. Similar results were seen in transgenic mice overexpressing PLP.
      With time, the endosomal/lysosomal accumulation of cholesterol and PLP led to an
      increase in the amount of detergent-insoluble cellular cholesterol and PLP. In
      addition, two fluorescent sphingolipids, BODIPY-lactosylceramide and 
      galactosylceramide, which under normal conditions are sorted to the Golgi
      apparatus, were missorted to perinuclear structures. This was also the case for
      the lipid raft marker glucosylphosphatidylinositol-yellow fluorescence protein,
      which under normal steady-state conditions is localized on the plasma membrane
      and to the Golgi complex. Taken together, we show that overexpression of PLP
      leads to the formation of endosomal/lysosomal accumulations of cholesterol and
      PLP, accompanied by the mistrafficking of raft components. We propose that these
      accumulations perturb the process of myelination and impair the viability of
      oligodendrocytes.

PMID- 11956231
TI  - Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and
      persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt
      coreceptor.
AB  - The low-density lipoprotein receptor-related protein (Lrp)-5 functions as a Wnt
      coreceptor. Here we show that mice with a targeted disruption of Lrp5 develop a
      low bone mass phenotype. In vivo and in vitro analyses indicate that this
      phenotype becomes evident postnatally, and demonstrate that it is secondary to
      decreased osteoblast proliferation and function in a Cbfa1-independent manner.
      Lrp5 is expressed in osteoblasts and is required for optimal Wnt signaling in
      osteoblasts. In addition, Lrp5-deficient mice display persistent embryonic eye
      vascularization due to a failure of macrophage-induced endothelial cell
      apoptosis. These results implicate Wnt proteins in the postnatal control of
      vascular regression and bone formation, two functions affected in many diseases.
      Moreover, these features recapitulate human osteoporosis-pseudoglioma syndrome,
      caused by LRP5 inactivation.

PMID- 11956234
TI  - Semaphorins as signals for cell repulsion and invasion.

PMID- 11956233
TI  - The cadherin-catenin adhesion system in signaling and cancer.

PMID- 11956235
TI  - Integrins in invasive growth.

PMID- 11956236
TI  - The plasma kallikrein-kinin system counterbalances the renin-angiotensin system.

PMID- 11956237
TI  - Chemorepulsion and thymocyte emigration.

PMID- 11956238
TI  - The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse
      model.
AB  - Dominant mutations in sarcomere protein genes cause hypertrophic cardiomyopathy,
      an inherited human disorder with increased ventricular wall thickness, myocyte
      hypertrophy, and disarray. To understand the early consequences of mutant
      sarcomere proteins, we have studied mice (designated alphaMHC(403/+)) bearing an
      Arg403Gln missense mutation in the alpha cardiac myosin heavy chain. We
      demonstrate that Ca(2+) is reduced in the sarcoplasmic reticulum of
      alphaMHC(403/+) mice, and levels of the sarcoplasmic reticulum Ca(2+)-binding
      protein calsequestrin are diminished in advance of changes in cardiac histology
      or morphology. Further evidence for dysregulation of sarcoplasmic reticulum
      Ca(2+) in these animals is seen in their decreased expression of the ryanodine
      receptor Ca(2+)-release channel and its associated membrane proteins and in an
      increase in ryanodine receptor phosphorylation. Early administration of the L
      type Ca(2+) channel inhibitor diltiazem restores normal levels of these
      sarcoplasmic reticular proteins and prevents the development of pathology in
      alphaMHC(403/+) mice. We conclude that disruption of sarcoplasmic reticulum
      Ca(2+) homeostasis is an important early event in the pathogenesis of this
      disorder and suggest that the use of Ca(2+) channel blockers in advance of
      established clinical disease could prevent hypertrophic cardiomyopathy caused by
      sarcomere protein gene mutations.

PMID- 11956239
TI  - A role for p53 in terminal epithelial cell differentiation.
AB  - Terminal epithelial cell differentiation is a crucial step in development. In the
      kidney, failure of terminal differentiation causes dysplasia, cystogenesis, and
      cancer. The present study provides multiple lines of evidence implicating the
      tumor suppressor protein p53 in terminal differentiation of the renal epithelium.
      In the developing kidney, p53 is highly enriched in epithelial cells expressing
      renal function genes (RFGs), such as receptors for vasoactive hormones, the
      sodium pump, and epithelial sodium and water channels. In comparison,
      proliferating renal progenitors express little if any p53 or RFGs. p53 binds to
      and transactivates the promoters of RFGs. In contrast, expression of a dominant
      negative mutant form of p53 inhibits endogenous RFG expression. Moreover, binding
      of endogenous p53 to the promoters of RFGs coincides with the differentiation
      process and is attenuated once renal epithelial cells are fully differentiated.
      Finally, p53-null pups exhibit a previously unrecognized aberrant renal phenotype
      and spatial disorganization of RFGs. Interestingly, the p53-related protein p73
      is unable to functionally compensate for the loss of p53 and fails to efficiently
      activate RFG transcription. We conclude that p53 promotes the biochemical and
      morphological differentiation of the renal epithelium. Aberrations in p53
      mediated terminal differentiation may therefore play a role in the pathogenesis
      of nephron dysgenesis and dysfunction.

PMID- 11956240
TI  - Elucidation of the thromboregulatory role of CD39/ectoapyrase in the ischemic
      brain.
AB  - Endothelial CD39 metabolizes ADP released from activated platelets. Recombinant
      soluble human CD39 (solCD39) potently inhibited ex vivo platelet aggregation in
      response to ADP and reduced cerebral infarct volumes in mice following transient
      middle cerebral artery occlusion, even when given 3 hours after stroke.
      Postischemic platelet and fibrin deposition were decreased and perfusion
      increased without increasing intracerebral hemorrhage. In contrast, aspirin did
      not increase postischemic blood flow or reduce infarction volume, but did
      increase intracerebral hemorrhage. Mice lacking the enzymatically active
      extracellular portion of the CD39 molecule were generated by replacement of exons
      4-6 (apyrase-conserved regions 2-4) with a PGKneo cassette. Although CD39 mRNA 3'
      of the neomycin cassette insertion site was detected, brains from these mice
      lacked both apyrase activity and CD39 immunoreactivity. Although their baseline
      phenotype, hematological profiles, and bleeding times were normal, cd39(-/-) mice
      exhibited increased cerebral infarct volumes and reduced postischemic perfusion.
      solCD39 reconstituted these mice, restoring postischemic cerebral perfusion and
      rescuing them from cerebral injury. These data demonstrate that CD39 exerts a
      protective thromboregulatory function in stroke.

PMID- 11956241
TI  - Promotion of osteoclast survival and antagonism of bisphosphonate-induced
      osteoclast apoptosis by glucocorticoids.
AB  - Glucocorticoids depress bone formation by inhibiting osteoblastogenesis and
      increasing osteoblast apoptosis. However, the role of bone resorption in the
      initial rapid phase of bone loss characteristic of glucocorticoid-induced
      osteoporosis is unexplained, and the reason for the efficacy of bisphosphonates
      in this condition remains unknown. We report that in murine osteoclast cultures,
      glucocorticoids prolonged the baseline survival of osteoclasts and antagonized
      bisphosphonate-induced caspase activation and apoptosis by a glucocorticoid
      receptor-mediated action. Consistent with the in vitro evidence, in a murine
      model of glucocorticoid-induced osteoporosis, the number of cancellous
      osteoclasts increased, even though osteoclast progenitor number was reduced.
      Moreover, in mice receiving both glucocorticoids and bisphosphonates, the
      expected proapoptotic effect of bisphosphonates on osteoclasts was abrogated, as
      evidenced by maintenance of osteoclast numbers and, additionally, loss of bone
      density. In contrast, bisphosphonate administration prevented glucocorticoid
      induced osteoblast apoptosis. These results indicate that the early loss of bone
      with glucocorticoid excess is caused by extension of the life span of pre
      existing osteoclasts, an effect not preventable by bisphosphonates. Therefore,
      the early beneficial effects of these agents must be due, in part, to prolonging
      the life span of osteoblasts.

PMID- 11956242
TI  - Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol
      acyltransferase 1.
AB  - Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT
      enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1
      deficient mice are resistant to diet-induced obesity through a mechanism
      involving increased energy expenditure. Here we show that these mice have
      decreased levels of tissue triglycerides, as well as increased sensitivity to
      insulin and to leptin. Importantly, DGAT1 deficiency protects against insulin
      resistance and obesity in agouti yellow mice, a model of severe leptin
      resistance. In contrast, DGAT1 deficiency did not affect energy and glucose
      metabolism in leptin-deficient (ob/ob) mice, possibly due in part to a
      compensatory upregulation of DGAT2 expression in the absence of leptin. Our
      results suggest that inhibition of DGAT1 may be useful in treating insulin
      resistance and leptin resistance in human obesity.

PMID- 11956243
TI  - Increased vascular permeability in C1 inhibitor-deficient mice mediated by the
      bradykinin type 2 receptor.
AB  - Heterozygosity for C1 inhibitor (C1INH) deficiency results in hereditary
      angioedema. Disruption of the C1INH gene by gene trapping enabled the generation
      of homozygous- and heterozygous-deficient mice. Mating of heterozygous-deficient
      mice resulted in the expected 1:2:1 ratio of wild-type, heterozygous, and
      homozygous-deficient offspring. C1INH-deficient mice showed no obvious phenotypic
      abnormality. However, following injection with Evans blue dye, both homozygous
      and heterozygous C1INH-deficient mice revealed increased vascular permeability in
      comparison with wild-type littermates. This increased vascular permeability was
      reversed by treatment with intravenous human C1INH, with a Kunitz domain plasma
      kallikrein inhibitor (DX88), and with a bradykinin type 2 receptor (Bk2R)
      antagonist (Hoe140). In addition, treatment of the C1INH-deficient mice with an
      angiotensin-converting enzyme inhibitor (captopril) increased the vascular
      permeability. Mice with deficiency of both C1INH and Bk2R demonstrated diminished
      vascular permeability in comparison with C1INH-deficient, Bk2R-sufficient mice.
      These data support the hypothesis that angioedema is mediated by bradykinin via
      Bk2R.

PMID- 11956244
TI  - Transcriptional induction of slit diaphragm genes by Lmx1b is required in
      podocyte differentiation.
AB  - LMX1B encodes a LIM-homeodomain transcription factor. Mutations in LMX1B cause
      nail-patella syndrome (NPS), an autosomal dominant disease with skeletal
      abnormalities, nail hypoplasia, and nephropathy. Expression of glomerular
      basement membrane (GBM) collagens is reduced in Lmx1b(-/-) mice, suggesting one
      basis for NPS nephropathy. Here, we show that Lmx1b(-/-) podocytes have reduced
      numbers of foot processes, are dysplastic, and lack typical slit diaphragms,
      indicating an arrest in development. Using antibodies to podocyte proteins
      important for podocyte function, we found that Lmx1b(-/-) podocytes express near
      normal levels of nephrin, synaptopodin, ZO-1, alpha3 integrin, and GBM laminins.
      However, mRNA and protein levels for CD2AP and podocin were greatly reduced,
      suggesting a cooperative role for these molecules in foot process and slit
      diaphragm formation. We identified several LMX1B binding sites in the putative
      regulatory regions of both CD2AP and NPHS2 (podocin) and demonstrated that LMX1B
      binds to these sequences in vitro and can activate transcription through them in
      cotransfection assays. Thus, LMX1B regulates the expression of multiple podocyte
      genes critical for podocyte differentiation and function. Our results indicate
      that reduced levels of proteins associated with foot processes and the glomerular
      slit diaphragm likely contribute, along with reduced levels of GBM collagens, to
      the nephropathy associated with NPS.

PMID- 11956246
TI  - Ectopic expression of KCNE3 accelerates cardiac repolarization and abbreviates
      the QT interval.
AB  - Regulatory subunit KCNE3 (E3) interacts with KCNQ1 (Q1) in epithelia, regulating
      its activation kinetics and augmenting current density. Since E3 is expressed
      weakly in the heart, we hypothesized that ectopic expression of E3 in cardiac
      myocytes might abbreviate action potential duration (APD) by interacting with Q1
      and augmenting the delayed rectifier current (I(K)). Thus, we transiently
      coexpressed E3 with Q1 and KCNE1 (E1) in Chinese hamster ovary cells and found
      that E3 coexpression increased outward current at potentials by > or = -80 mV and
      accelerated activation. We then examined the changes in cardiac electrophysiology
      following injection of adenovirus-expressed E3 into the left ventricular cavity
      of guinea pigs. After 72 hours, the corrected QT interval of the
      electrocardiogram was reduced by approximately 10%. APD was reduced by >3-fold in
      E3-transduced cells relative to controls, while E-4031-insensitive I(K) and
      activation kinetics were significantly augmented. Based on quantitative modeling
      of a transmural cardiac segment, we demonstrate that the degree of QT interval
      abbreviation observed results from electrotonic interactions in the face of
      limited transduction efficiency and that heterogeneous transduction of E3 may
      actually potentiate arrhythmias. Provided that fairly homogeneous ectopic
      ventricular expression of regulatory subunits can be achieved, this approach may
      be useful in enhancing repolarization and in treating long QT syndrome.

PMID- 11956245
TI  - The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes.
AB  - Patients with nail-patella syndrome often suffer from a nephropathy, which
      ultimately results in chronic renal failure. The finding that this disease is
      caused by mutations in the transcription factor LMX1B, which in the kidney is
      expressed exclusively in podocytes, offers the opportunity for a better
      understanding of the renal pathogenesis. In our analysis of the nephropathy in
      nail-patella syndrome, we have made use of the Lmx1b knockout mouse. Transmission
      electron micrographs showed that glomerular development in general and the
      differentiation of podocytes in particular were severely impaired. The glomerular
      capillary network was poorly elaborated, fenestrae in the endothelial cells were
      largely missing, and the glomerular basement membrane was split. In addition
      podocytes retained a cuboidal shape and did not form foot processes and slit
      diaphragms. Expression of the alpha4 chain of collagen IV and of podocin was also
      severely reduced. Using gel shift assays, we demonstrated that LMX1B bound to two
      AT-rich sequences in the promoter region of NPHS2, the gene encoding podocin. Our
      results demonstrate that Lmx1b regulates important steps in glomerular
      development and establish a link between three hereditary kidney diseases: nail
      patella syndrome (Lmx1b), steroid-resistant nephrotic syndrome (podocin), and
      Alport syndrome (collagen IV alpha4).

PMID- 11956247
TI  - Normal myelopoiesis but abnormal T lymphocyte responses in vitamin D receptor
      knockout mice.
AB  - The vitamin D receptor (VDR) is a transcription factor that mediates the actions
      of its ligand, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], which can promote
      monocyte/macrophage differentiation and inhibit proliferation and cytokine
      production by activated T lymphocytes. In this study, VDR knockout (KO) mice were
      used to investigate the possible role of VDR in hematopoiesis. The relative
      number of red and white peripheral blood cells and the percentage of bone marrow
      macrophages did not differ between VDR KO and wild-type mice. 12-O
      tetradecanoylphorbol-13-acetate, but not 1,25(OH)(2)D(3), induced differentiation
      of bone marrow-committed myeloid stem cells from VDR KO mice to
      monocytes/macrophages. Production of IL-18, a Th1-promoting cytokine, was reduced
      in macrophages from these mice. Antigen-stimulated spleen cells from VDR KO mice
      showed an impaired Th1 cell response and had decreased expression of STAT4, a Th1
      cell transcription factor. These results demonstrate the absolute requirement of
      VDR for 1,25(OH)(2)D(3)-induced monocyte/macrophage differentiation but show that
      monocyte/macrophage differentiation can occur in the absence of this receptor.
      The observed reduction in Th1 population in these mutant mice may be explained by
      a loss of macrophage IL-18 production or a suppression of STAT4 expression by
      activated splenocytes.

PMID- 11956248
TI  - Thymocyte emigration is mediated by active movement away from stroma-derived
      factors.
AB  - T cells leave the thymus at a specific time during differentiation and do not
      return despite elaboration of known T cell chemoattractants by thymic stroma. We
      observed differentiation stage-restricted egress of thymocytes from an artificial
      thymus in which vascular structures or hemodynamics could not have been playing a
      role. Hypothesizing that active movement of cells away from a thymic product may
      be responsible, we demonstrated selective reduction in emigration from primary
      thymus by inhibitors of active movement down a concentration gradient
      (chemofugetaxis). Immature intrathymic precursors were insensitive to an
      emigration signal, whereas mature thymocytes and peripheral blood T cells were
      sensitive. Thymic stroma was noted to elaborate at least two proteins capable of
      inducing emigration, one of which was stromal cell-derived factor-1. Thymic
      emigration is mediated, at least in part, by specific fugetaxis-inducing factors
      to which only mature cells respond.

PMID- 11956250
TI  - Screening for lung cancer: no longer a taboo subject.

PMID- 11956249
TI  - Mapping myasthenia gravis-associated T cell epitopes on human acetylcholine
      receptors in HLA transgenic mice.
AB  - Susceptibility to myasthenia gravis (MG) is positively linked to expression of
      HLA-DQ8 and DR3 molecules and negatively linked to expression of the DQ6
      molecule. To elucidate the molecular basis of this association, we have induced
      experimental autoimmune MG (EAMG) in mice transgenic for HLA-DQ8, DQ6, and DR3,
      and in DQ8xDQ6 and DQ8xDR3 F(1) transgenic mice, by immunization with human
      acetylcholine receptor (H-AChR) in CFA. Mice expressing transgenes for one or
      both of the HLA class II molecules positively associated with MG (DQ8 and DR3)
      developed EAMG. T cells from DQ8 transgenic mice responded well to three
      cytoplasmic peptide sequences of H-AChR (alpha320-337, alpha304-322, and alpha419
      437), of which the response to alpha320-337 was the most intense. DR3 transgenic
      mice also responded to this sequence very strongly. H-AChR- and alpha320-337
      peptide-specific lymphocyte responses were restricted by HLA class II molecules.
      Disease resistance in DQ6 transgenic mice was associated with reduced synthesis
      of anti-AChR IgG, IgG(2b), and IgG(2c) Ab's and reduced IL-2 and IFN-gamma
      secretion by H-AChR- and peptide alpha320-337-specific lymphocytes. Finally, we
      show that DQ8 imparts susceptibility to EAMG and responsiveness to an epitope
      within the sequence alpha320-337 as a dominant trait.

PMID- 11956251
TI  - Epirubicin, cisplatin, and fluorouracil in gastric and esophageal cancer: a step
      ahead?

PMID- 11956252
TI  - Sensitivity of renal cell cancer to nonmyeloablative allogeneic hematopoietic
      cell transplantations: unusual or unusually important?

PMID- 11956253
TI  - The local-regionally advanced nasopharyngeal carcinoma jigsaw puzzle: where does
      the chemotherapy piece fit?

PMID- 11956254
TI  - Sphincter preservation for rectal cancer: fact or fiction?

PMID- 11956255
TI  - The Mayo Lung Cohort: a regression analysis focusing on lung cancer incidence and
      mortality.
AB  - PURPOSE: The Mayo Lung Project has been interpreted as negative because it failed
      to demonstrate a significant mortality reduction among those randomized to chest
      x-ray and cytology. In contrast, survival suggests that screening is highly
      effective. This report was undertaken to analyze the trial as a closed cohort
      study, in an effort to identify predictors of lung cancer incidence and
      mortality, and to determine whether survival or mortality was unbiased. PATIENTS
      AND METHODS: The Mayo Lung Cohort comprised all 9,192 randomized individuals. Cox
      proportional hazards regression was used both to determine predictors of
      incidence and mortality in the population and to identify predictors of mortality
      among cases. Survival analyses using intent-to-treat principles and measuring
      survival from randomization were used to evaluate length bias and lead-time bias.
      Multivariate Cox regression was used to investigate the extent to which the data
      are consistent with overdiagnosis. RESULTS: Cox regression demonstrates that, in
      addition to age and smoking, randomization to screening predicted increased lung
      cancer incidence (hazard ratio, 1.30; 95% confidence interval [CI], 1.06 to
      1.60). Predictors of mortality were similar, except randomization to screening
      was not significant (hazard ratio, 1.06; 95% CI, 0.83 to 1.37). Among cases,
      survival was significantly superior in the experimental population. Higher
      incidence in the experimental group accounts for the mortality/survival
      discrepancy. Both lead-time and length biases can be excluded, because survival
      from randomization was superior in the experimental population. Overdiagnosis is
      eliminated because resection was the only significant multivariate predictor of
      survival. Overall, 50% of resected and 0% of unresected cases were cured.
      CONCLUSION: Survival was superior in the screened population, and this advantage
      was not attributable to lead-time bias, length bias, or overdiagnosis bias.
      Mortality was biased, because incidence differences confounded the ability of
      mortality to reflect the true effect of screening. Indeed, survival provided an
      unbiased surrogate for cure in the Mayo Lung Cohort.

PMID- 11956256
TI  - Intraoperative sentinel lymph node mapping in non-small-cell lung cancer improves
      detection of micrometastases.
AB  - PURPOSE: Lymph node metastases are the most significant prognostic factor in
      localized non-small-cell lung cancer (NSCLC). Nodal micrometastases may not be
      detected with current standard histologic methods. We performed intraoperative
      technetium-99m ((99m)Tc) sentinel lymph node (SN) mapping in patients with
      resectable NSCLC. This study aimed to identify the first station of nodal
      drainage of operable lung cancers. Serial section histology and
      immunohistochemistry were used to validate the SN and to identify the presence of
      micrometastatic disease. PATIENTS AND METHODS: One hundred patients with
      potentially resectable suspected NSCLC were enrolled. At thoracotomy, the primary
      tumor was injected with 0.25 to 2 mCi (99m)Tc. Intraoperative scintigraphic
      readings of both the primary tumor and lymph nodes were obtained with a hand-held
      gamma counter. Anatomic resection with a mediastinal node dissection was then
      performed. RESULTS: Nine of the 100 patients did not have NSCLC (seven benign
      lesions and two metastatic tumors) and were excluded. Seventy-eight (86%) of 91
      patients had a SN identified and a complete resection. Sixty-nine (88.5%) out of
      the 78 SNs were classified as true-positive with no metastases found in other
      intrathoracic lymph nodes without concurrent SN involvement. In nine patients,
      the SN was the only positive node. In seven of these nine patients, the SN was
      found to harbor only micrometastatic disease. CONCLUSION: Intraoperative SN
      mapping with (99m)Tc is an accurate way to identify the first site of lymphatic
      tumor drainage in NSCLC. This method may also improve the precision of pathologic
      staging.

PMID- 11956257
TI  - Long-term results of combined-modality therapy in resectable non-small-cell lung
      cancer.
AB  - PURPOSE: Assessment of long-term results of combined-modality therapy for
      resectable non-small-cell lung cancer is hampered by insufficient follow-up and
      small patient numbers. To evaluate this, we reviewed our collective experience.
      PATIENTS AND METHODS: This study was a retrospective chart review recording
      demographics, tumor stage, treatment, and outcome of consecutive patients
      undergoing surgery. Survival was analyzed by Kaplan-Meier, and prognostic factors
      were analyzed by log-rank and Cox regression. RESULTS: From January 1993 to
      December 1999, 470 patients were treated, with follow-up in 446: 27 stage I, 55
      stage II, 316 stage III, 43 stage IV (solitary M1), and five uncertain.
      Chemotherapy was mitomycin/vinblastine/cisplatin (174 patients [39.0%]),
      carboplatin/paclitaxel (148 [33.2%]), and other combination (124 [27.8%]); 75
      patients (16.8%) received induction radiation. Resection was complete in 77.4%,
      incomplete in 8.3%, attempted but with gross residual disease afterward in 1.8%,
      and not performed in 12.6%. Pathologic complete response occurred in 20 patients
      (4.5%). With median follow-up of 31.0 months for patients still alive, median and
      3-year survival for pathologic stages 0, I, II, III, and IV were more than 90
      months, 73%; 42 months, 52%; 23 months, 35%; 16 months, 28%; and 16 months, 23%
      (P <.001). In a multivariate analysis, age, complete resection, pathologic stage,
      and pneumonectomy, but not induction regimen, significantly influenced survival.
      CONCLUSION: Although pathologic complete response outside the protocol setting is
      low, survival of this large patient cohort is comparable to that of patients in
      published combined-modality trials. Survival is significantly influenced by
      patient age, complete resection, pathologic stage, and pneumonectomy. These
      results can help guide standard clinical practice and emphasize the need for
      novel induction regimens.

PMID- 11956258
TI  - Prospective randomized trial comparing mitomycin, cisplatin, and protracted
      venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU
      in advanced esophagogastric cancer.
AB  - PURPOSE: We report the results of a prospectively randomized study that compared
      the combination of epirubicin, cisplatin, and protracted venous-infusion
      fluorouracil (PVI 5-FU) (ECF) with the combination of mitomycin, cisplatin, and
      PVI 5-FU (MCF) in previously untreated patients with advanced esophagogastric
      cancer. PATIENTS AND METHODS: Five hundred eighty patients with adenocarcinoma,
      squamous carcinoma, or undifferentiated carcinoma were randomized to receive
      either ECF (epirubicin 50 mg/m(2) every 3 weeks, cisplatin 60 mg/m(2) every 3
      weeks and PVI 5-FU 200 mg/m(2)/d) or MCF (mitomycin 7 mg/m(2) every 6 weeks,
      cisplatin 60 mg/m(2) every 3 weeks, and PVI 5-FU 300 mg/m(2)/d) and analyzed for
      survival, response, toxicity, and quality of life (QOL). RESULTS: The overall
      response rate was 42.4% (95% confidence interval [CI], 37% to 48%) with ECF and
      44.1% (95% CI, 38% to 50%) with MCF (P =.692). Toxicity was tolerable, and there
      were only two toxic deaths. ECF resulted in more grade 3/4 neutropenia and grade
      2 alopecia, but MCF caused more thrombocytopenia and plantar-palmar erythema.
      Median survival was 9.4 months with ECF and 8.7 months with MCF (P =.315); at 1
      year, 40.2% (95% CI, 34% to 46%) of ECF and 32.7% (95% CI, 27% to 38%) of MCF
      patients were alive. Median failure-free survival was 7 months with both
      regimens. Global QOL scores were better with ECF at 3 and 6 months. CONCLUSION:
      This study confirms response, survival, and QOL benefits of ECF observed in a
      previous randomized study. The equivalent efficacy of MCF was demonstrated, but
      QOL was superior with ECF. ECF remains one of the reference treatments for
      advanced esophagogastric cancer.

PMID- 11956260
TI  - Allogeneic stem-cell transplantation of renal cell cancer after nonmyeloablative
      chemotherapy: feasibility, engraftment, and clinical results.
AB  - PURPOSE: To evaluate the feasibility and safety of nonmyeloablative allogeneic
      stem-cell transplantation in patients with metastatic renal cell cancer (RCC) and
      to evaluate efficacy with respect to engraftment and tumor regression. PATIENTS
      AND METHODS: Between February 1999 and June 2001, patients with refractory,
      metastatic RCC were screened for enrollment. A fludarabine and cyclophosphamide
      based conditioning regimen was used. Patients received granulocyte-macrophage
      colony-stimulating factor-mobilized, unmanipulated stem cells from a 6/6 HLA
      matched sibling donor. Prophylaxis against graft rejection and graft-versus-host
      disease (GVHD) included tacrolimus and mycophenolate mofetil. RESULTS: A total of
      284 patients with metastatic RCC were seen during this time period. Eighty-four
      patients who had siblings available for HLA typing were actively screened for
      enrollment, and 15 patients have undergone treatment. Durable donor engraftment
      was achieved in one of the first four patients treated. Patients no. 5 through 15
      received a more immunosuppressive conditioning regimen, and all have achieved
      sustained donor engraftment. In the 12 patients with at least 180 days of follow
      up, acute GVHD has occurred in two patients and chronic GVHD in six patients,
      with four transplant-related mortalities. Four partial responses have been
      observed (response rate, 33% in all patients; 44% in the nine patients with
      sustained donor engraftment). CONCLUSION: Nonmyeloablative allogeneic stem-cell
      transplantation is feasible for a minority of patients with metastatic RCC.
      Adequately immunosuppressive conditioning is required for sustained donor
      engraftment, which is required for an antitumor response. Acute and chronic GVHD
      are the major causes of substantial morbidity and mortality. Metastatic RCC is
      susceptible to a graft-versus-tumor effect promoted by allogeneic stem-cell
      transplantation.

PMID- 11956259
TI  - Minimal residual disease in gastric cancer: evidence of an independent prognostic
      relevance of urokinase receptor expression by disseminated tumor cells in the
      bone marrow.
AB  - PURPOSE: To study the invasion-related molecule urokinase-type plasminogen
      activator receptor (u-PAR) expressed by disseminated tumor cells as a biologic
      predictor of poor survival in a large prospective series of patients with gastric
      cancer. PATIENTS AND METHODS: In 156 gastric cancer patients (prospective
      series), disseminated tumor cells in the bone marrow and the u-PAR expressed by
      these tumor cells were determined by cytokeratin (CK) 18 immunocytochemistry and
      u-PAR/CK18 double immunocytochemistry. RESULTS: In contrast to the mere detection
      of disseminated tumor cells at primary surgery, the additional evidence of u-PAR
      on these cells correlated significantly with pathologic T stage (P =.0474) and
      the expression of u-PAR (P =.0093) and plasminogen-activator inhibitor 1 (P
      =.0145) in the primary tumor (immunohistochemistry, chi(2)). Kaplan-Meier
      analysis revealed no association with prognosis for the mere detection of
      disseminated tumor cells. In contrast, a significant association was seen between
      detection of u-PAR on these cells and shorter disease-free (P <.0001) and overall
      survival (P <.0001). Multivariate analysis revealed that u-PAR on disseminated
      tumor cells at the time of primary surgery is an independent prognostic factor
      for disease-free (95% confidence interval [CI], 1.72 to 3.21; P =.024) and
      overall survival (P =.0049; relative risk, 2.89; 95% CI, 1.92 to 4.30).
      CONCLUSION: This is the first large study to show that u-PAR, detected on
      disseminated tumor cells in the bone marrow, is an independent prognostic
      parameter in gastric cancer, in contrast to the mere detection of minimal
      residual disease (MRD). u-PAR may be a promising marker to define a critical
      subpopulation of disseminated tumor cells and a target to eliminate MRD.
      Molecular phenotyping of MRD is critical for defining its individual clinical
      relevance.

PMID- 11956261
TI  - Analysis of clinical stage T2 prostate cancer: do current subclassifications
      represent an improvement?
AB  - PURPOSE: The purpose of this study was to determine whether the extent of
      palpable cancer within the prostate predicts outcome after radical prostatectomy.
      PATIENTS AND METHODS: We combined prospectively collected data on 1,755
      consecutive clinical stage T2 patients treated with radical prostatectomy alone
      at four institutions. According to the 1992 American Joint Committee on Cancer
      tumor-node-metastasis system, 645 (37%) were T2a, 758 (43%) were T2b, and 352
      (20%) were T2c. Kaplan-Meier and proportional hazards regression analyses were
      performed on the 1992 and 1997 T2 subclassifications. After controlling for the
      effects of prostate-specific antigen (PSA) and biopsy Gleason sum, the two
      staging systems were compared for their ability to predict recurrence-free
      survival (RFS). Adjusted RFS curves were constructed using the corrected group
      prognosis method. RESULTS: Follow-up ranged from 1 to 166 months (median, 26
      months). Cancer recurred in 417 (24%) of the T2 patients. The 1992 (P =.005) but
      not the 1997 (P =.100) T2 subclassification predicted outcome after controlling
      for PSA and Gleason sum. After covariate adjustment, RFS was 7% higher at 5 years
      in the 1992 T2a subcategory relative to the T2b subcategory. CONCLUSION: The 1992
      American Joint Committee on Cancer system is superior to the 1997 system, and the
      former adds prognostic information to a model containing pretreatment PSA and
      Gleason sum. These results suggest that 1992 T2 subclassification derived from
      palpable findings improves prognostication over the 1997 subclassification.

PMID- 11956262
TI  - Activity of oxaliplatin in patients with relapsed or cisplatin-refractory germ
      cell cancer: a study of the German Testicular Cancer Study Group.
AB  - PURPOSE: To investigate the efficacy and toxicity of oxaliplatin, a
      diaminocyclohaxane platinum derivative with incomplete cross-resistance to
      cisplatin in patients with relapsed or cisplatin-refractory germ cell cancer.
      PATIENTS AND METHODS: Thirty-two patients with nonseminomatous cisplatin
      refractory germ cell cancer or relapsed disease after high-dose chemotherapy
      (HDCT) plus autologous stem-cell support were treated with single-agent
      oxaliplatin 60 mg/m(2) on days 1, 8, and 15 repeated every 4 weeks (group 1; n =
      16) or oxaliplatin 130 mg/m(2) given on days 1 and 15 of a 4-week cycle (group 2;
      n = 16). Patients were pretreated with a median of seven (range, three to 13)
      cisplatin-containing treatment cycles; 78% had received carboplatin/etoposide
      based HDCT before oxaliplatin therapy. Twenty-seven patients (84%) were
      considered refractory (n = 20; 63%) or absolutely refractory (n = 7; 22%) to
      cisplatin therapy. RESULTS: Overall, four patients achieved a partial remission
      (13%; 95% confidence interval, 1% to 24%). Two additional patients achieved
      disease stabilization. All responses were observed in cisplatin-refractory
      patients, including three who had not responded to previous HDCT. Patients
      received a median two cycles of oxaliplatin with a median cumulative dose of 350
      mg/m(2). Hematologic toxicity was generally mild, with five patients developing
      grade 3/4 thrombocytopenia. Nonhematologic side effects consisted mainly of
      nausea/vomiting. One patient developed grade 3 neurotoxicity. CONCLUSION:
      Considering the particularly unfavorable prognostic characteristics of this
      patient population compared with patients from previous trials for new drugs in
      germ cell cancer, eg, paclitaxel and gemcitabine, a 13% overall response rate and
      a 19% response rate in the group treated with oxaliplatin 130 mg/m(2) seems to be
      of interest. Oxaliplatin may be a palliative treatment option for this patient
      population, and evaluation in combination regimens is warranted.

PMID- 11956265
TI  - Implications of microscopic satellites of the primary and extracapsular lymph
      node spread in patients with high-risk melanoma: pathologic corollary of Eastern
      Cooperative Oncology Group Trial E1690.
AB  - PURPOSE: To correlate the presence of extracapsular spread (ECS) of regional
      nodal metastases, and micrometastasis near the primary tumor, with disease
      outcome in the intergroup study E1690 in relation to the impact of recombinant
      interferon-alfa (rIFN alpha)-2b. PATIENTS AND METHODS: E1690 included 642
      patients with American Joint Committee on Cancer stage IIB or III cutaneous
      melanoma. Patients were randomized into high- and low-dose rIFN alpha-2b
      treatment arms and an observation arm. Pathologic slides were reviewed for
      selected parameters from at least half of the subjects in all three arms.
      Evaluation of the primary tumor included notations regarding ulceration, mitotic
      activity, thickness, microscopic satellites (MS), and nodal ECS on a standardized
      pathology form. These data were collated in relation to relapse-free survival
      (RFS) and overall survival (OS) at 50 months' follow-up and studied using Cox
      regression analysis. RESULTS: Ulceration, mitotic activity, thickness, and size
      of tumor-bearing lymph nodes did not show a statistically significant correlation
      with either OS or RFS across all treatment arms. The presence of MS was
      correlated with RFS (P =.0008) and OS (P =.05). ECS correlated with RFS (hazard
      ratio = 1.44, P =.032) but not OS (P =.11). CONCLUSION: The presence of MS (in 6%
      [18 of 308 patients]) had a significant adverse impact on both RFS (P =.0008) and
      OS (P =.053). Ulceration, mitotic activity, thickness, and number of positive
      lymph nodes had no significant effect on OS in this subset study (univariate or
      multivariate Cox analysis). The presence of ECS in lymph nodes had a significant
      adverse effect on RFS (P =.032) but not on OS.

PMID- 11956263
TI  - Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in
      locoregionally advanced nasopharyngeal carcinoma: progression-free survival
      analysis of a phase III randomized trial.
AB  - PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy
      (RT) and chemotherapy. This randomized phase III trial compared concurrent
      cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC.
      PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal
      size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8
      weeks concurrently with radical RT (CRT) or RT alone. The primary end point was
      progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients
      were randomized. Baseline patient characteristics were comparable in both arms.
      There were significantly more toxicities, including mucositis, myelosuppression,
      and weight loss in the CRT arm. There were no treatment-related deaths in the CRT
      arm, and one patient died during treatment in the RT-alone arm. At a median
      follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT
      alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI],
      0.93 to 2.00). The treatment effect had a significant covariate interaction with
      tumor stage, and a subgroup analysis demonstrated a highly significant difference
      in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328
      (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was
      statistically significantly different in favor of the CRT arm (P =.016).
      CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in
      endemic areas. Although PFS was not significantly different between the
      concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was
      significantly prolonged in patients with advanced tumor and node stages.

PMID- 11956264
TI  - Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results
      from a phase III randomized trial.
AB  - PURPOSE: The addition of cytokines to chemotherapy has produced encouraging
      results in advanced melanoma. In this phase III trial, we compared the effects of
      chemotherapy (cisplatin, vinblastine, and dacarbazine [CVD]) with those of
      sequential biochemotherapy consisting of CVD plus interleukin-2 and interferon
      alfa-2b. PATIENTS AND METHODS: Metastatic melanoma patients who had not
      previously received chemotherapy were stratified by prognostic factors and given
      chemotherapy or biochemotherapy. CVD consisted of dacarbazine (days 1 and 22) and
      cisplatin and vinblastine (days 1 to 4 and 22 to 25). Biochemotherapy involved
      CVD with vinblastine reduced 25% plus interleukin-2 by 24-hour continuous
      infusion (on days 5 to 8, 17 to 20, and 26 to 29) and interferon alfa-2b by
      subcutaneous injection (on days 5 to 9, 17 to 21, and 26 to 30). Response was
      assessed every 6 weeks. RESULTS: Among 190 patients enrolled, 91 were assessable
      for biochemotherapy and 92 for chemotherapy. Ten percent of the patients were
      alive a median of 52 months from start of therapy. Response rates were 48% for
      biochemotherapy and 25% for chemotherapy (P =.001); six patients given
      biochemotherapy and two given chemotherapy had complete responses. Median time to
      progression (TTP) was 4.9 months for biochemotherapy and 2.4 months for
      chemotherapy (P =.008); median survival was 11.9 and 9.2 months, respectively (P
      =.06). The influence of treatment on TTP and survival was confirmed in
      multivariate analyses with other prognostic factors not included in the original
      stratification. Biochemotherapy produced substantially more constitutional,
      hemodynamic, and myelosuppressive toxic effects. CONCLUSION: Cytokines
      substantially augment the antitumor activity of chemotherapy at the expense of
      considerable toxicity in patients with metastatic melanoma.

PMID- 11956266
TI  - Adjuvant immunotherapy of resected, intermediate-thickness, node-negative
      melanoma with an allogeneic tumor vaccine: overall results of a randomized trial
      of the Southwest Oncology Group.
AB  - PURPOSE: Patients with clinically negative nodes constitute over 85% of new
      melanoma cases. There is no adjuvant therapy for intermediate-thickness, node
      negative melanoma patients. PATIENTS AND METHODS: The Southwest Oncology Group
      conducted a randomized phase III trial of an allogeneic melanoma vaccine for 2
      years versus observation in patients with intermediate-thickness (1.5 to 4.0 mm
      or Clark's level IV if thickness unknown), clinically or pathologically node
      negative melanoma (T3N0M0). RESULTS: Six hundred eighty-nine patients were
      accrued over 4.5 years; 89 patients (13%) were ineligible. Surgical node staging
      was performed in 24%, the remainder were clinical N0. Thirteen eligible patients
      refused assigned treatment: seven on the observation arm and six on the vaccine
      arm. Most vaccine patients experienced mild to moderate local toxicity, but 26
      (9%) experienced grade 3 toxicity. After a median follow-up of 5.6 years, there
      were 107 events (tumor recurrences or deaths) among the 300 eligible patients
      randomized to vaccine compared with 114 among the 300 eligible patients
      randomized to observation (hazard ratio, 0.92; Cox-adjusted P(2) = 0.51). There
      was no difference in vaccine efficacy among patients with tumors < or = 3 mm or >
      3 mm. CONCLUSION: This represents one of the largest randomized, controlled
      trials of adjuvant vaccine therapy in human cancer reported to date. Compliance
      with randomization was excellent, with only 2% refusing assigned therapy. There
      is no evidence of improved disease-free survival among patients randomized to
      receive vaccine, although the power to detect a small but clinically significant
      difference was low. Future investigations of adjuvant vaccine approaches for
      patients with intermediate-thickness melanoma should involve larger numbers of
      patients and ideally should include sentinel node biopsy staging.

PMID- 11956269
TI  - Breast cancer screening in women previously treated for Hodgkin's disease: a
      prospective cohort study.
AB  - PURPOSE: Young women who are exposed to chest irradiation for Hodgkin's disease
      (HD) are at increased risk of breast cancer; this study investigated patient
      awareness of breast cancer risk and patient screening behavior and assessed the
      utility of mammographic screening in HD survivors. PATIENTS AND METHODS: This is
      a prospective cohort study of 90 female long-term survivors of HD who had been
      treated > or = 8 years previously with mantle irradiation (current age, 24 to 51
      years). Participants completed surveys of their perceptions of breast cancer risk
      and screening behaviors and received written recommendations for breast
      examinations and mammography. Annual follow-up was conducted through medical
      records, telephone, and/or mailed questionnaires. RESULTS: At baseline, women
      were often unaware of their increased risk of breast cancer; 40% (35 of 87)
      reported themselves to be at equal or lower risk than women of the same age. Only
      47% (41 of 87) reported having had a mammogram in the previous 24 months. Women
      who had received information from an oncologist were more likely to assess
      correctly their risk than women who received information from other sources (P
      <.001). Ten women developed 12 breast cancers (ductal carcinoma-in-situ [n = 2],
      invasive ductal carcinoma [n = 10]) during the study; two were diagnosed at study
      entry, and 10 during follow-up (median, 3.1 years). All cancers were evident on
      mammogram, and eight of 10 invasive cancers were node negative. CONCLUSION:
      Practitioners who care for women after HD therapy need to educate patients
      regarding their risks and begin early screening. Screening by mammography can
      detect small, node-negative breast cancers in these patients.

PMID- 11956268
TI  - Prognostic factors for survival in adult patients with cerebral low-grade glioma.
AB  - PURPOSE: To identify prognostic factors for survival in adult patients with
      cerebral low-grade glioma (LGG), to derive a prognostic scoring system, and to
      validate results using an independent data set. PATIENTS AND METHODS: European
      Organization for Research and Treatment of Cancer (EORTC) trial 22844 and EORTC
      trial 22845 are the largest phase III trials ever carried out in adult patients
      with LGG. The trials were designed to investigate the dosage and timing of
      postoperative radiotherapy in LGG. Cox analysis was performed on 322 patients
      from EORTC trial 22844 (construction set), and the results were validated on 288
      patients from trial 22845 (validation set). Patients with pilocytic astrocytomas
      were excluded from this prognostic factor analysis. RESULTS: Multivariate
      analysis on the construction set showed that age > or = 40 years, astrocytoma
      histology subtype, largest diameter of the tumor > or = 6 cm, tumor crossing the
      midline, and presence of neurologic deficit before surgery were unfavorable
      prognostic factors for survival. The total number of unfavorable factors present
      can be used to determine the prognostic score. Presence of up to two of these
      factors identifies the low-risk group, whereas a higher score identifies high
      risk patients. The validity of the multivariate model and of the scoring system
      was confirmed in the validation set. CONCLUSION: In adult patients with LGG,
      older age, astrocytoma histology, presence of neurologic deficits before surgery,
      largest tumor diameter, and tumor crossing the midline were important prognostic
      factors for survival. These factors can be used to identify low-risk and high
      risk patients.

PMID- 11956267
TI  - Adjuvant immunotherapy of resected, intermediate-thickness, node-negative
      melanoma with an allogeneic tumor vaccine: impact of HLA class I antigen
      expression on outcome.
AB  - PURPOSE: An association between expression of > or = two of five HLA class I
      antigens (HLA-A2, HLA-A28, HLA-B44, HLA-B45, and HLA-C3; collectively called M5)
      and response to an allogeneic melanoma vaccine (Melacine; Corixa Corporation,
      Seattle, WA) has been described in stage IV melanoma. This study investigated
      whether class I antigen expression impacted relapse-free survival (RFS) after
      adjuvant therapy with this vaccine. PATIENTS AND METHODS: We performed class I
      (HLA-A, HLA-B, and HLA-C) serotyping on patients enrolled onto Southwest Oncology
      Group Trial 9035, a randomized, observation-controlled, phase III trial of
      adjuvant Melacine. All patients had clinically node-negative cutaneous melanoma
      (1.5 to 4.0 mm). Interactions between treatment and class I antigen expression
      were tested. Analyses involved all serotyped patients and were adjusted for tumor
      thickness, method of nodal staging, sex, ulceration, and primary tumor site.
      RESULTS: HLA typing was performed on 553 (80%) of the 689 enrolled patients (294
      vaccinated and 259 observed). Expression of > or = two M5 antigens was associated
      with a superior vaccine treatment effect. Among patients who matched > or = two
      of the M5, the 97 vaccine-treated patients had improved RFS compared with the 78
      observation patients (5-year relapse-free survival, 83% v 59%; P =.0002). The
      major components of this effect were contributed by HLA-A2 and HLA-C3. Among
      those who were HLA-A2-positive and/or HLA-C3-positive, the 5-year RFS for
      vaccinated patients was 77%, compared with 64% for observation (P =.004). There
      was no impact of HLA-A2 and/or HLA-C3 expression among observation patients.
      CONCLUSION: This prospective analysis indicates a highly significant benefit of
      adjuvant therapy with Melacine among patients expressing > or = two of the M5
      class I antigens, validating a prior observation in stage IV disease. HLA-A2 and
      HLA-C3 contributed most to this effect. Processed melanoma peptides found in
      Melacine may be presented by HLA-A2 and HLA-C3 and play a role in preventing
      relapse in vaccinated patients.

PMID- 11956270
TI  - Decision analysis of prophylactic surgery or screening for BRCA1 mutation
      carriers: a more prominent role for oophorectomy.
AB  - PURPOSE: BRCA1 mutation carriers have a high risk of developing breast and
      ovarian cancer. Carriers may opt for prophylactic surgery and screening. Recent
      data suggesting that prophylactic oophorectomy reduces breast cancer risk have
      been incorporated in a decision analysis. METHODS: A Markov model was developed
      to compare LE and QALE following four strategies: (1) prophylactic mastectomy and
      prophylactic oophorectomy (PMPO), (2) screening for breast cancer and
      prophylactic oophorectomy (BSPO), (3) prophylactic mastectomy and screening for
      ovarian cancer (PMOS), and (4) screening for breast and ovarian cancer (BSOS).
      The analysis was performed for a high (85% breast cancer, 63% ovarian cancer) and
      medium (56% breast cancer, 16% ovarian cancer) risk level. Utilities for the
      health states after prophylactic surgery were obtained from mutation carriers.
      Other model parameter values were obtained from the literature. Sensitivity
      analyses were performed. RESULTS: When compared with BSOS, the average gain in LE
      for 30-year-old carriers in the high (medium) risk group was 11.7 (6.6) years for
      PMPO, 9.5 (5.3) years for BSPO, and 4.9 (4.4) years for PMOS. For 30-year-old
      carriers, BSPO had a QALE advantage when PO was performed before age 40. In the
      medium-risk group, there was a stronger advantage for BSPO when QALE was
      considered. CONCLUSION: PMPO is the most effective strategy to prolong life.
      However, if patient preferences were taken into account, BSPO tends to be a
      better strategy in most women at medium risk or in young women at high risk when
      PO was performed before age 40.

PMID- 11956271
TI  - Long-term survival and competing causes of death in patients with early-stage
      Hodgkin's disease treated at age 50 or younger.
AB  - PURPOSE: To analyze the long-term survival and the pattern and timing of excess
      mortality in patients with early-stage Hodgkin's disease. PATIENTS AND METHODS:
      Between 1969 and 1997, 1,080 patients age 50 or younger were treated for clinical
      stage IA to IIB Hodgkin's disease. Overall survival was determined, and
      prognostic factors were assessed. Relative risk and absolute excess risk (AR) of
      mortality were calculated for the entire cohort and by prognostic groups (on the
      basis of B symptoms, mediastinal status, and number of sites, modified from the
      European Organization for Research and Treatment of Cancer). RESULTS: The median
      follow-up was 12 years. The 15- and 20-year Kaplan-Meier survival estimates were
      84% and 78%, respectively. Cox proportional hazards models showed that number of
      involved sites (P =.006), mediastinal status (P =.02), and histology (P =.02)
      were independent predictors of death from all causes. The AR of mortality in
      patients with a favorable prognosis increased over time, whereas for those with
      an unfavorable prognosis, the AR peaked in the first 5 years, predominantly from
      Hodgkin's disease. The relative risk of mortality from all causes, causes other
      than Hodgkin's disease, second tumors, and cardiac disease remained significantly
      elevated more than 20 years after treatment. CONCLUSION: Patients treated for
      early-stage Hodgkin's disease have a sustained excess mortality risk despite good
      control of the disease. Treatment reduction efforts in patients with early-stage,
      favorable-prognosis disease should continue, but for patients with an unfavorable
      prognosis, modified treatment may not be advisable. The excess mortality noted
      beyond two decades underscores the importance of long-term follow-up care in
      patients treated for Hodgkin's disease.

PMID- 11956272
TI  - How sociodemographics, presence of oncology specialists, and hospital cancer
      programs affect accrual to cancer treatment trials.
AB  - PURPOSE: We chose to examine the impact of socioeconomic factors on accrual to
      National Cancer Institute (NCI)-sponsored cancer treatment trials. PATIENTS AND
      METHODS: We estimated the geographic and demographic cancer burden in the United
      States and then identified 24,332 patients accrued to NCI-sponsored cancer
      treatment trials during a 12-month period. Next, we examined accrual by age, sex,
      geographic residence, health insurance status, health maintenance organization
      market penetration, several proxy measures of socioeconomic status, the
      availability of an oncologist, and the presence of a hospital with an approved
      multidisciplinary cancer program. RESULTS: Pediatric patients were accrued to
      clinical trials at high levels, whereas after adolescence, only a small
      percentage of cancer patients were enrolled onto clinical trials. There were few
      differences by sex. Black males as well as Asian-American and Hispanic adults
      were accrued to clinical trials at lower rates than white cancer patients of the
      same age. Overall, the highest observed accrual was in suburban counties.
      Compared with the United States population, patients enrolled onto clinical
      trials were significantly less likely to be uninsured and more like to have
      Medicare health insurance. Geographic areas with higher socioeconomic levels had
      higher levels of clinical trial accruals. The number of oncologists and the
      presence of approved cancer programs both were significantly associated with
      increased accrual to clinical trials. CONCLUSION: We must work to increase the
      number of adults who enroll onto trials, especially among the elderly. Ongoing
      partnership with professional societies may be an effective approach to
      strengthen accrual to clinical trials.

PMID- 11956273
TI  - Association of depressive syndrome and early deaths among patients after stem
      cell transplantation for malignant diseases.
AB  - PURPOSE: The association of depression and increased mortality in the general
      population, and also various medical conditions, is well documented. However,
      depression is not well studied in the setting of hematopoietic stem-cell
      transplantation (HSCT). We examined the association between depressive syndrome
      and survival after HSCT. PATIENTS AND METHODS: A total of 193 patients who
      received autologous or allogeneic HSCT from Brigham and Women's Hospital or Dana
      Farber Cancer Institute were evaluated prospectively. The self-rated Likert
      scaled symptom checklist, the SF-36, and the Spitzer Quality of Life Index Scale
      were administered. Outcomes evaluated included survival and quality of life.
      RESULTS: Sixty-seven patients (35%) satisfied the criteria for depressive
      syndrome. The 1-year probability of survival for the depressed and nondepressed
      patients was 85% (95% confidence interval [CI], 74% to 92%) and 94% (95% CI, 89%
      to 97%), respectively (P =.04). In multivariable modeling, depressed patients
      have a three-fold greater risk of dying than nondepressed patients (95% CI, 1.07
      to 8.30; P =.04) between 6 and 12 months after HSCT after adjusting for other
      prognostic factors. Global inferiority in quality of life was observed in the
      depressed cohort when last measured at 24 months after transplantation.
      CONCLUSION: Depressive syndrome after HSCT is associated with decreased survival,
      at least from 6 to 12 months after transplantation. Persistence of this
      association after controlling for possible confounding factors suggests that
      depression may be more than simply a marker for concurrent ill health. This study
      raises an interesting hypothesis as to whether psychological or pharmacologic
      intervention for depression after HSCT can improve survival and/or quality of
      life.

PMID- 11956274
TI  - Place of death and its predictors for local patients registered at a
      comprehensive cancer center.
AB  - PURPOSE: To help with planning of a palliative care program, we reviewed the
      place of death of patients who were registered at our comprehensive cancer center
      and explored factors that predicted death in the hospital versus death at home.
      PATIENTS AND METHODS: A retrospective study was undertaken of local patients who
      were registered at the University of Texas M.D. Anderson Cancer Center and died
      during the 1997/1998 fiscal year. Data from the institutional tumor registry and
      from the State of Texas Bureau of Vital Statistics file were collected and
      analyzed. The main outcome measures were place of death, patient characteristics
      associated with place of death, and time from registration at the institution to
      death. RESULTS: Of 1,793 local patients, 251 (14%) died at M.D. Anderson Cancer
      Center; the remaining 86% died elsewhere. A total of 617 (34%) died at home, and
      929 (52%) died in an acute hospital setting (including M.D. Anderson). A total of
      1,040 (58%) died within 2 years of registration. The risk of hospital death
      versus home death increased for patients with cancer at a hematologic site (odds
      ratio [OR], 4.4; 95% confidence interval [CI], 2.8 to 6.8) and black ethnicity
      (OR, 1.9; 95% CI, 1.4 to 2.6) and decreased for patients who paid with Medicare
      (OR, 0.71; 95% CI, 0.57 to 0.90). CONCLUSION: Most patients died in an acute care
      hospital setting and within 2 years of registration. Our data show some
      predictors of hospital death for cancer patients and suggest that better hospital
      palliative care services and integrated palliative care systems that bridge
      community and acute hospitals are needed.

PMID- 11956275
TI  - Attitudes of terminally ill cancer patients about euthanasia and assisted
      suicide: predominance of psychosocial determinants and beliefs over symptom
      distress and subsequent survival.
AB  - PURPOSE: Although euthanasia and physician-assisted suicide (PAS) are
      controversial issues, the views of those most affected, terminal patients, are
      seldom explored. Our objective was to assess whether the attitudes about
      euthanasia/PAS of terminally ill cancer patients were determined by their
      symptomatic distress. PATIENTS AND METHODS: We conducted a survey of 100 patients
      with terminal cancer. Statements related to the legalization of euthanasia/PAS
      were scored using Likert scales. We also asked patients how often they had
      considered ending their lives. Their responses were analyzed in relation to
      disease characteristics, including an assessment of symptomatic severity,
      sociodemographic features, general beliefs about the suffering of cancer
      patients, and survival. RESULTS: Most patients (69%) supported euthanasia or PAS
      for one or more situations. The association between these attitudes and symptoms
      was weak, consistent in univariate analysis only for shortness of breath. No
      significant associations were observed with pain, nausea, well-being, loss of
      appetite, depression, or subsequent survival. Agreement with euthanasia was
      significantly related to male sex, lack of religious beliefs, and general beliefs
      about the suffering of cancer patients and their families. In multivariate
      analysis, the only characteristics that remained statistically associated with
      support were the strength of religious beliefs and the perception that patients
      with cancer are a heavy burden on their families. Frequency of suicidal ideation
      was associated with poor well-being, depression, anxiety, and shortness of
      breath, but not with other somatic symptoms such as pain, nausea, and loss of
      appetite. CONCLUSION: Symptom intensity had limited impact on the attitudes about
      euthanasia of terminally ill cancer patients. Our findings suggest that patient
      views are primarily determined by psychosocial traits and beliefs, as opposed to
      disease severity or symptomatic distress.

PMID- 11956276
TI  - Pilot study of iodine-131-metaiodobenzylguanidine in combination with
      myeloablative chemotherapy and autologous stem-cell support for the treatment of
      neuroblastoma.
AB  - PURPOSE: The survival for children with relapsed or metastatic neuroblastoma
      remains poor. More effective regimens with acceptable toxicity are required to
      improve prognosis. Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) selectively
      targets radiation to catecholamine-producing cells, including neuroblastoma
      cells. A pilot study was performed to examine the feasibility of a novel regimen
      combining (131)I-MIBG and myeloablative chemotherapy with autologous stem-cell
      rescue. PATIENTS AND METHODS: Twelve patients with neuroblastoma were treated
      after relapse (five patients) or after induction therapy (seven patients). Eight
      patients had metastatic and four had localized disease at the time of therapy.
      All patients received (131)I-MIBG 12 mCi/kg on day -21, followed by carboplatin
      (1,500 mg/m(2)), etoposide (800 mg/m(2)), and melphalan (210 mg/m(2))
      administered from day -7 to day -4. Autologous peripheral-blood stem cells or
      bone marrow were infused on day 0. Engraftment, toxicity, and response rates were
      evaluated. RESULTS: The (131)I-MIBG infusion and myeloablative chemotherapy were
      both well tolerated. Grade 2 to 3 oral mucositis was the predominant
      nonhematopoietic toxicity, occurring in all patients. The median times to
      neutrophil (> or = 0.5 x 10(3)/microL) and platelet (> or = 20 x 10(3)/microL)
      engraftment were 10 and 28 days, respectively. For the eight patients treated
      with metastatic disease, three achieved complete response and two had partial
      responses by day 100 after transplantation. CONCLUSION: Treatment with (131)I
      MIBG in combination with myeloablative chemotherapy and hematopoietic stem-cell
      rescue is feasible with acceptable toxicity. Future study is warranted to examine
      the efficacy of this novel therapy.

PMID- 11956277
TI  - High-dose chemotherapy in the treatment of relapsed osteosarcoma: an Italian
      sarcoma group study.
AB  - PURPOSE: To study the feasibility and activity of two courses of high-dose
      chemotherapy (HDCT) in patients with osteosarcoma in metastatic relapse. PATIENTS
      AND METHODS: Patients with high-grade osteosarcoma in metastatic relapse
      (multiple metastases or solitary metastasis at intervals of less than 30 months)
      were eligible for study. High-dose chemotherapy consisted of carboplatin and
      etoposide followed by stem-cell rescue. A second course was planned 4 to 6 weeks
      after the first. Surgery was performed before or after HDCT. RESULTS: Thirty-two
      patients were enrolled onto the study. At the end of the treatment, 25 patients
      were in complete remission (CR), six were alive with disease progression, and one
      died of toxicity. At present, 14 patients are alive with a median survival time
      of 23 months from study entry: four are in first CR, three are in second CR, and
      one is in fourth CR. Six patients are alive with disease. Eighteen patients (56%)
      died: 17 of disease and one of toxicity. Transplantation-related mortality was
      3.1%. The relapse or progression disease rate was 84.4%. The 3-year overall
      survival rate is 20% and the 3-year disease-free survival rate is 12%.
      CONCLUSION: HDCT combined with surgery is feasible and can induce CR in a large
      portion of patients. Two points, however, need to be considered: only patients
      who are chemosensitive to induction treatment can obtain CR after HDCT, and the
      length of remission is short, because most patients relapse. Thus novel
      strategies are needed to maintain the remission status or to treat patients who
      do not respond to induction treatment.

PMID- 11956278
TI  - Phase I study of the cyclin-dependent kinase inhibitor flavopiridol in
      combination with paclitaxel in patients with advanced solid tumors.
AB  - PURPOSE: Preclinical studies indicate that the cyclin-dependent kinase inhibitor
      flavopiridol potentiates the induction of apoptosis by paclitaxel, provided
      paclitaxel is followed by flavopiridol. We therefore designed a phase I clinical
      trial of sequential paclitaxel and flavopiridol. PATIENTS AND METHODS: Paclitaxel
      was administered at a fixed dose, as either a 24- or 3-hour infusion on day 1,
      followed by a 24-hour infusion of flavopiridol on day 2. Doses of flavopiridol
      were escalated in successive cohorts according to a modified Fibonacci design.
      Flavopiridol pharmacokinetics were obtained on all patients. RESULTS: Dose
      limiting neutropenia developed with 24-hour paclitaxel doses of 135 and 100
      mg/m(2) and flavopiridol doses of 10 and 20 mg/m(2), respectively. With 3-hour
      paclitaxel at 100 mg/m(2), flavopiridol could be escalated to 70 mg/m(2) without
      dose-limiting toxicity. With 3-hour paclitaxel next escalated to 135 mg/m(2),
      dose-limiting neutropenia and pulmonary toxicity occurred when flavopiridol was
      escalated to 94 mg/m(2). This did not correlate with any change in flavopiridol
      or paclitaxel pharmacokinetics. At a 3-hour paclitaxel dose of 175 mg/m(2), dose
      limiting pulmonary toxicity occurred in only one patient at flavopiridol doses
      under 94 mg/m(2). Clinical activity was observed in patients with esophagus,
      lung, and prostate cancer, including patients who had progressed on paclitaxel.
      CONCLUSION: The recommended phase II doses will be a 3-hour infusion of
      paclitaxel at 175 mg/m(2) on day 1 followed by a 24-hour infusion of flavopiridol
      at 70 mg/m(2) on day 2. Flavopiridol dose escalations to 80 mg/m(2) are possible.
      At these doses, toxicities are manageable and clinical activity is promising.

PMID- 11956279
TI  - Atrasentan, an endothelin-receptor antagonist for refractory adenocarcinomas:
      safety and pharmacokinetics.
AB  - PURPOSE: Endothelin receptors, particularly the ET(A) receptor, have been shown
      to participate in the pathophysiology of prostate and other cancers. Atrasentan,
      an endothelin antagonist, binds selectively to the ET(A) receptor. This study
      evaluated the safety, pharmacokinetics, and maximum-tolerated dose of atrasentan
      in cancer patients. PATIENTS AND METHODS: Patients who were 18 years or older and
      had histologically confirmed adenocarcinoma refractory to therapy enrolled in
      this 28-day, open-label, phase I study. Enrollment was planned for cohorts of
      three patients at doses escalating from 10 to 140 mg/d. When any patient had dose
      limiting toxicity, that cohort was expanded. The primary outcome variable was
      safety; secondary outcome variables were pharmacokinetics, tumor response, and
      pain relief. RESULTS: Thirty-one cancer patients (14 prostate) were treated at
      daily atrasentan doses of 10, 20, 30, 45, 60, and 75 mg (n = 3 to 8 per cohort).
      The most common adverse events, such as rhinitis, headache, asthenia, and
      peripheral edema, were reversible on drug discontinuation and responded to
      symptom-specific treatment. Reversible hemodilution was apparent in laboratory
      findings and weight gain. Clinically significant headache was the dose-limiting
      adverse event; the maximum-tolerated dose was 60 mg/d. Pharmacokinetics were dose
      proportional across the 10- to 75-mg dose range. Atrasentan was rapidly absorbed;
      the time to maximum observed concentration was approximately 1.5 hours. The
      terminal elimination half-life was approximately 24 hours, and steady-state
      plasma concentrations were achieved within 7 days. Decreases in prostate-specific
      antigen and pain relief were noted in a patient subset. CONCLUSION: Adverse
      events were consistent with atrasentan's pharmacologic vasodilatory effect.
      Linear, dose-proportional pharmacokinetics suggest that atrasentan can be easily
      and consistently dosed.

PMID- 11956280
TI  - High-dose chemotherapy in poor-prognosis adult small round-cell tumors: clinical
      and molecular results from a prospective study.
AB  - PURPOSE: The prognosis of metastatic/high-risk localized small round-cell tumors
      (SRCTs) treated conventionally is dismal. In this phase II study, we explored a
      high-dose chemotherapy (HD-CT) approach and analyzed the clinical significance of
      fusion transcripts detection. PATIENTS AND METHODS: From June 1997 to November
      1999, 28 SRCT patients (median age, 26 years; 14 peripheral primitive
      neuroectodermal tumors [pPNETs], seven rhabdomyosarcomas [RMSs], and seven
      desmoplastic small round-cell tumors [DSRCTs]) received induction chemotherapy
      with ifosfamide, epirubicin, and vincristine followed by HD-CT. Local treatment
      (radiotherapy and/or surgery) was performed when possible. Molecular analysis was
      performed on peripheral-blood and leukapheresis products by reverse-transcriptase
      polymerase chain reaction. RESULTS: Overall response (OR) was 65% (18 of 28),
      with 40% complete response and 25% partial response. According to histology, the
      OR rate was 86% in pPNET and 43% in both RMS DSRCT. With a median follow-up of 35
      months, median overall survival was 16 months and median progression-free
      survival (PFS) was 10 months. PFS was statistically better in pPNET than other
      histologic types (P =.0045). No correlation was found between the fusion
      transcript and clinical outcome during follow-up. Furthermore, transcript
      detection in leukapheretic products was not of prognostic significance.
      CONCLUSION: Intensive HD-CT seems to enhance the response rate and survival when
      compared with conventional treatment in poor-prognosis pPNET. The poor results of
      this treatment in RMS and DSRCT do not support the inclusion of such an approach
      in these patient subsets. No definitive conclusions can currently be drawn
      concerning the clinical implications of the detection of fusion transcripts
      during treatment or follow-up.

PMID- 11956281
TI  - Oncologists' attitudes toward and practices in giving bad news: an exploratory
      study.
AB  - PURPOSE: To examine the attitudes and practices of oncologists in disclosure of
      unfavorable medical information to cancer patients. METHODS: A questionnaire was
      administered to a group of physicians who attended the 1999 Annual Meeting of the
      American Society of Clinical Oncology. The questionnaire assessed demographic and
      practice-related information and the frequency of patient encounters in which
      unfavorable cancer-related information was disclosed. Participants were also
      asked about difficulties they had when approaching stressful discussions and
      communication strategies used in giving unfavorable information. RESULTS: The
      questionnaire was completed by 167 oncologists. Sixty-four percent were medical
      oncologists. Thirty-eight percent practiced in North America, 26% practiced in
      Europe, 13% practiced in South America, and 13% practiced in Asia. Participants
      gave bad news to patients an average of 35 times per month. Discussing no further
      curative treatment and hospice was reported as most difficult. In disclosing the
      cancer diagnosis and prognosis, physicians from Western countries were less
      likely to withhold unfavorable information from the patient at the family's
      request, avoid the discussion entirely, use euphemisms, and give treatments known
      not to be effective so as not to destroy hope than physicians from other
      countries. There was significant variability in opinions regarding the best time
      to discuss resuscitation, with 18% of respondents believing that it should be
      done close to the end of life. CONCLUSION: There was significant variability in
      how physicians approach information disclosure to cancer patients. Factors such
      as geographical region and cultural and family variables may be important
      influences in this process.

PMID- 11956282
TI  - Carcinoembryonic antigen as a target for therapeutic anticancer vaccines: a
      review.
AB  - PURPOSE: To describe the features of carcinoembryonic antigen (CEA) that are
      important for its use in vaccination approaches and review the clinical
      experience with therapeutic vaccines targeting CEA. METHODS: A PubMed search was
      performed on CEA, along with various qualifiers such as cancer vaccines,
      epitopes, and function. Relevant articles were reviewed. RESULTS: CEA is a member
      of the immunoglobulin supergene family and may play a role in tumorigenesis. CEA
      protein is processed and presented on major histocompatibility complex (MHC)
      proteins for multiple alleles, including HLA A2, A3, and A24. T lymphocytes from
      healthy volunteers and cancer patients can recognize the processed epitopes of
      CEA and can become activated to lyse CEA-expressing tumors. Therapeutic
      vaccination approaches that have targeted CEA include vaccination with
      recombinant CEA protein, CEA anti-idiotype antibodies, and dendritic cells pulsed
      with agonist epitopes of CEA. Humoral responses have predominantly been induced
      with the first two approaches, whereas CD4 and CD8 responses, disease
      stabilization, and even objective clinical responses have been seen with the
      dendritic cell approach. Recently, CEA-poxvirus vectors encoding CEA and
      costimulatory molecules such as B7.1 have been shown to be safe and to induce
      increases in the frequency of T-cell precursors that recognize processed epitopes
      of CEA presented on MHC class 1 molecules. Disease stabilization has been seen in
      up to 37% of patients treated with these vaccines. CONCLUSION: Tolerance to CEA
      in patients with cancer can be overcome with several different vaccination
      approaches, and such vaccinations are safe and immunologically active. Poxvirus
      based vaccines can reproducibly generate T-cell responses to CEA and to tumors
      expressing CEA. Clinical activity has been seen with poxvirus or dendritic cell
      approaches. Other approaches are also being explored.

PMID- 11956283
TI  - Sentinel-node technique will change the design of clinical trials in malignant
      melanoma.

PMID- 11956284
TI  - Perioperative chemotherapy in patients with node-negative postmenopausal breast
      cancer.

PMID- 11956285
TI  - Implantable cardiac defibrillators may be damaged by radiation therapy.

PMID- 11956286
TI  - Tumor lysis syndrome at the beginning of thalidomide therapy for multiple
      myeloma.

PMID- 11956287
TI  - Perinatal blockade of b7-1 and b7-2 inhibits clonal deletion of highly pathogenic
      autoreactive T cells.
AB  - A number of in vitro studies have suggested that costimulatory molecules B7-1 and
      B7-2 and their receptor CD28 can promote clonal deletion, and limited in vivo
      studies have indicated that CD28 is involved in the clonal deletion of some T
      cells. However, the significance of B7-mediated clonal deletion in preventing
      autoimmune diseases has not been studied systematically. Here we report that the
      perinatal blockade of B7-1 and B7-2 substantially inhibits the clonal deletion of
      T cells in the thymus and leads to an accumulation of T cells capable of inducing
      fatal multiorgan inflammation. These results reveal a critical role for
      costimulatory molecules B7-1 and B7-2 in deleting pathogenic autoreactive T cells
      in the thymus. The critical role of B7-1 and B7-2 in T cell clonal deletion may
      explain, at least in part, the paradoxical increase of autoimmune disease in mice
      deficient for this family of costimulatory molecules, such as cytotoxic T
      lymphocyte associated molecule 4, CD28, and B7-2. The strong pathogenicity of the
      self-reactive T cells supports a central hypothesis in immunology, which is that
      clonal deletion plays an important role in preventing autoimmune diseases.

PMID- 11956288
TI  - Defective angiogenesis in the inflammatory granulation tissue in histidine
      decarboxylase-deficient mice but not in mast cell-deficient mice.
AB  - We have analyzed the role of histamine in the angiogenesis of the granulation
      tissue in histidine decarboxylase-deficient (HDC(-/-)) mice, mast cell-deficient
      mice (WBB6F1-W/W(V)), and their corresponding wild-type mice (HDC(+/+) and
      WBB6F(1)(+/+)). In HDC(+/+) mice, subcutaneous implantation of a cotton thread in
      the dorsum induced granulation tissue formation with angiogenesis, while the
      topical injection of anti-vascular endothelial growth factor (VEGF) IgG strongly
      suppressed them. In HDC(-/-) mice which showed lower VEGF levels in the
      granulation tissue, there was notably less angiogenesis and granulation tissue
      formation than in HDC(+/+) mice. The topical injection of histamine or the H(2)
      agonist dimaprit rescued the defective angiogenesis and granulation tissue
      formation in HDC(-/-) mice. There was no significant difference in the
      granulation tissue formation and angiogenesis between WBB6F1-W/W(V) and
      WBB6F1(+/+) mice. In addition, macrophages in the granulation tissue were found
      to express HDC. Our findings indicate that histamine derived from non-mast cells
      plays a significant role in the angiogenesis of the inflammatory granulation
      tissue.

PMID- 11956289
TI  - Link between organ-specific antigen processing by 20S proteasomes and CD8(+) T
      cell-mediated autoimmunity.
AB  - Adoptive transfer of cross-reactive HSP60-specific CD8(+) T cells into
      immunodeficient mice causes autoimmune intestinal pathology restricted to the
      small intestine. We wondered whether local immunopathology induced by CD8(+) T
      cells can be explained by tissue-specific differences in proteasome-mediated
      processing of major histocompatibility complex class I T cell epitopes. Our
      experiments demonstrate that 20S proteasomes of different organs display a
      characteristic composition of alpha and beta chain subunits and produce distinct
      peptide fragments with respect to both quality and quantity. Digests of HSP60
      polypeptides by 20S proteasomes show most efficient generation of the pathology
      related CD8(+) T cell epitope in the small intestine. Further, we demonstrate
      that the organ-specific potential to produce defined T cell epitopes reflects
      quantities that are relevant for cytotoxic T lymphocyte recognition. We propose
      tissue-specific antigen processing by 20S proteasomes as a potential mechanism to
      control organ-specific immune responses.

PMID- 11956290
TI  - Predominant role of T cell receptor (TCR)-alpha chain in forming preimmune TCR
      repertoire revealed by clonal TCR reconstitution system.
AB  - The CDR3 regions of T cell receptor (TCR)-alpha and -beta chains play central
      roles in the recognition of antigen (Ag)-MHC complex. TCR repertoire is created
      on the basis of Ag recognition specificity by CDR3s. To analyze the potential
      spectrum of TCR-alpha and -beta to exhibit Ag specificity and generate TCR
      repertoire, we established hundreds of TCR transfectants bearing a single TCR
      alpha or -beta chain derived from a cytotoxic T cell (CTL) clone, RT-1, specific
      for HIVgp160 peptide, and randomly picked up TCR-beta or -alpha chains.
      Surprisingly, one-third of such TCR-beta containing random CDR3 beta from naive T
      cells of normal mice could reconstitute the antigen-reactive TCR coupling with RT
      1 TCR-alpha. A similar dominant function of TCR-alpha in forming Ag-specific TCR,
      though low-frequency, was obtained for lymphocytic choriomeningitis virus
      specific TCR. Subsequently, we generated TCR-alpha and/or -beta transgenic (Tg)
      mice specific for HIVgp160 peptide, and analyzed the TCR repertoire of Ag
      specific CTLs. Similar to the results from TCR reconstitution, TCR-alpha Tg
      generated CTLs with heterogeneous TCR-beta, whereas TCR-beta Tg-induced CTLs
      bearing a single TCR-alpha. These findings of Ag recognition with minimum
      involvement of CDR3 beta expand our understanding regarding the flexibility of
      the spectrum of TCR and suggest a predominant role of TCR-alpha chain in
      determining the preimmune repertoire of Ag-specific TCR.

PMID- 11956291
TI  - Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate
      interleukin 4 gene expression.
AB  - Proteins of the nuclear factor of activated T cells (NFAT) family of
      transcription factors are critical for lymphocyte activation in the immune
      system. In particular, NFATs are important regulators of inducible IL-4 gene
      expression. Interferon regulatory factor 4 (IRF4) is an immune system-restricted
      interferon regulatory factor that is required for lymphocyte activation, but its
      molecular functions in the T lineage remain to be elucidated. We demonstrate that
      IRF4 potently synergizes with NFATc2 to specifically enhance NFATc2-driven
      transcriptional activation of the IL-4 promoter. This function is dependent on
      the physical interaction of IRF4 with NFATc2. IRF4 synergizes with NFATc2 and the
      IL-4-inducing transcription factor, c-maf, to augment IL-4 promoter activity as
      well as to elicit significant levels of endogenous IL-4 production. Furthermore,
      naive T helper cells from mice lacking IRF4 are compromised severely for the
      production of IL-4 and other Th2 cytokines. The identification of IRF4 as a
      partner for NFATc2 in IL-4 gene regulation provides an important molecular
      function for IRF4 in T helper cell differentiation.

PMID- 11956292
TI  - Presentation of the same glycolipid by different CD1 molecules.
AB  - Five CD1 molecules are expressed in humans and it is unclear whether they have
      specialized or redundant functions. We found that sulfatide is a promiscuous CD1
      binding ligand and have isolated T cell clones that are specific for sulfatide
      and restricted by distinct CD1 molecules. These clones have been used to compare
      the capacity of different CD1 to present the same glycolipid, to induce effector
      functions, and to form persistent immunogenic complexes. CD1a, CD1b, and CD1c
      molecules similarly load sulfatide on the cell surface without processing, and
      prime Th1 and Th2 responses. Stimulation by sulfatide-loaded CD1a persists much
      longer than that by CD1b and CD1c in living cells. Use of recombinant soluble
      CD1a confirmed the prolonged capacity to stimulate T cells. Moreover, other
      glycosphingolipids bind to all CD1, which suggests the presence of additional
      promiscuous ligands. Thus, group I CD1 molecules present an overlapping set of
      self-glycolipids, even though they are quite divergent from an evolutionary point
      of view.

PMID- 11956294
TI  - Ligand binding sites of inducible costimulator and high avidity mutants with
      improved function.
AB  - Interaction between inducible costimulator (ICOS) and its ligand is implicated in
      the induction of cell-mediated and humoral immune responses. However, the
      molecular details of this interaction are unknown. We report here a mutagenesis
      analysis of residues in ICOS that are critical for ligand binding. A three
      dimensional model of the extracellular immunoglobulin-like domain of ICOS was
      used to map the residues conserved within the CD28 family. This analysis
      identified a surface patch containing the characteristic "PPP" sequence and is
      conserved in human and mouse ICOS. Mutations in this region of human ICOS reduce
      or abolish ligand binding. Our results suggest that the ligand binding site in
      ICOS maps to a region overlapping yet distinct from the CD80/CD86 binding sites
      in CD28 and cytotoxic T lymphocyte antigen (CTLA)-4. Thus, the analysis suggests
      that differences in ligand binding specificity between these related
      costimulatory molecules have evolved by utilization of overlapping regions with
      different patterns of conserved and nonconserved residues. Two site-specific
      mutants generated in the course of our studies bound ICOS ligand with higher
      avidity than wild-type ICOS. An S76E mutant protein of ICOS blocked T cell
      costimulatory function of ICOS ligand and inhibited T cell response to allogeneic
      antigens superior to wild-type ICOS. Our studies thus identified critical
      residues involving in ICOS receptor-ligand interaction and provide new modulators
      for immune responses.

PMID- 11956293
TI  - HIV-1 Nef interacts with inositol trisphosphate receptor to activate calcium
      signaling in T cells.
AB  - HIV-1 pathogenicity factor Nef has been shown to modulate calcium signaling in
      host cells, but the underlying molecular mechanisms have remained unclear. Here
      we show that calcium/calcineurin-dependent activation of nuclear factor of
      activated T cells (NFAT) by Nef in Jurkat T cells requires the endoplasmic
      reticulum-resident inositol trisphosphate receptor (IP(3)R), but yet does not
      involve increase in phospholipase-C gamma 1 (PLC gamma 1)-catalyzed production of
      IP(3) or depletion of IP(3)-regulated intracellular calcium stores. Nef could be
      coprecipitated with endogenous IP(3)R type-1 (IP(3)R1) from Nef-transfected
      Jurkat T cells as well as from HIV-infected primary human peripheral mononuclear
      cells. Thus, the Nef/IP(3)R1-interaction defines a novel T cell receptor
      independent mechanism by which Nef can promote T cell activation, and appears to
      involve atypical IP(3)R-triggered activation of plasma membrane calcium influx
      channels in a manner that is uncoupled from depletion of intracellular calcium
      stores.

PMID- 11956295
TI  - Structural basis of cytochrome c presentation by IE(k).
AB  - The COOH-terminal peptides of pigeon and moth cytochrome c, bound to mouse IE(k),
      are two of the most thoroughly studied T cell antigens. We have solved the
      crystal structures of the moth peptide and a weak agonist-antagonist variant of
      the pigeon peptide bound to IE(k). The moth peptide and all other peptides whose
      structures have been solved bound to IE(k), have a lysine filling the p9 pocket
      of IE(k). However, the pigeon peptide has an alanine at p9 shifting the lysine to
      p10. Rather than kinking to place the lysine in the anchor pocket, the pigeon
      peptide takes the extended course through the binding groove, which is
      characteristic of all other peptides bound to major histocompatibility complex
      (MHC) class II. Thus, unlike MHC class I, in which peptides often kink to place
      optimally anchoring side chains, MHC class II imposes an extended peptide
      conformation even at the cost of a highly conserved anchor residue. The
      substitution of Ser for Thr at p8 in the variant pigeon peptide induces no
      detectable surface change other than the loss of the side chain methyl group,
      despite the dramatic change in recognition by T cells. Finally, these structures
      can be used to interpret the many published mutational studies of these ligands
      and the T cell receptors that recognize them.

PMID- 11956296
TI  - Regulated expression of human histocompatibility leukocyte antigen (HLA)-DO
      during antigen-dependent and antigen-independent phases of B cell development.
AB  - Human histocompatibility leukocyte antigen (HLA)-DO, a lysosomal resident major
      histocompatibility complex class II molecule expressed in B cells, has previously
      been shown to be a negative regulator of HLA-DM peptide loading function. We
      analyze the expression of DO in human peripheral blood, lymph node, tonsil, and
      bone marrow to determine if DO expression is modulated in the physiological
      setting. B cells, but not monocytes or monocyte-derived dendritic cells, are
      observed to express this protein. Preclearing experiments demonstrate that
      approximately 50% of HLA-DM is bound to DO in peripheral blood B cells. HLA-DM
      and HLA-DR expression is demonstrated early in B cell development, beginning at
      the pro-B stage in adult human bone marrow. In contrast, DO expression is
      initiated only after B cell development is complete. In all situations, there is
      a striking correlation between intracellular DO expression and cell surface class
      II-associated invariant chain peptide expression, which suggests that DO
      substantially inhibits DM function in primary human B cells. We report that the
      expression of DO is markedly downmodulated in human germinal center B cells.
      Modulation of DO expression may provide a mechanism to regulate peptide loading
      activity and antigen presentation by B cells during the development of humoral
      immune responses.

PMID- 11956298
TI  - Arthritogenic monoclonal antibodies from K/BxN mice.
AB  - Arthritis in the K/BxN mouse model is provoked by pathogenic antibodies (Abs)
      directed against a ubiquitously expressed protein, glucose-6-phosphate isomerase
      (GPI). To begin dissecting the repertoire of arthritogenic immunoglobulins (Igs)
      in the K/BxN model, and to provide a basis for comparison with RA patients we
      have generated anti-GPI monoclonal Abs (mAbs) from spontaneously activated B
      cells in the lymphoid organs of arthritic mice. B cell clones with anti-GPI
      specificities were present at extraordinarily high frequencies in the spleen, and
      less frequently in other lymphoid organs and in the synovial fluid. None of the
      anti-GPI mAbs induced arthritis when injected individually into healthy
      recipients, but most were effective when combined in pairs or larger pools.
      Arthritogenic combinations depended on mAbs of the IgG1 isotype, which bound to
      GPI with Kd in the 10(-9) M range, with no indication of cooperative binding
      between complementing pairs. Pathogenicity was not associated with recognition of
      a particular epitope, but the ability to form mAb/GPI multimers by simultaneous
      recognition of different epitopes was clearly required, consistent with the known
      role of complement and FcRs in this model. Sequence analysis revealed structural
      similarities amongst the mAbs, indicating that a particular subset of B cells may
      evade tolerance in K/BxN mice, and that affinity maturation by somatic mutation
      likely takes place. These results confirm that GPI itself, rather than a cross
      reactive molecule, is the target of pathogenic Igs.

PMID- 11956297
TI  - Germinal center B cells regulate their capability to present antigen by
      modulation of HLA-DO.
AB  - Peptide acquisition by MHC class II molecules is catalyzed by HLA-DM (DM). In B
      cells, HLA-DO (DO) inhibits or modifies the peptide exchange activity of DM. We
      show here that DO protein levels are modulated during B cell differentiation.
      Remarkably, germinal center (GC) B cells, which have low levels of DO relative to
      naive and memory B cells, are shown to have enhanced antigen presentation
      capabilities. DM protein levels also were somewhat reduced in GC B cells;
      however, the ratio of DM to DO in GC B cells was substantially increased,
      resulting in more free DM in GC B cells. We conclude that modulation of DM and DO
      in distinct stages of B cell differentiation represents a mechanism by which B
      cells regulate their capacity to function as antigen-presenting cells. Efficient
      antigen presentation in GC B cells would promote GC B cell-T cell interactions
      that are essential for B cells to survive positive selection in the GC.

PMID- 11956300
TI  - Innate immunity as a hired gun: but is it rheumatoid arthritis?

PMID- 11956299
TI  - Interleukin 4 reduces expression of inhibitory receptors on B cells and abolishes
      CD22 and Fc gamma RII-mediated B cell suppression.
AB  - Inhibitory receptors CD22, Fc gamma RII (CD32), CD72, and paired immunoglobulin
      like receptor (PIR)-B are critically involved in negatively regulating the B cell
      immune response and in preventing autoimmunity. Here we show that interleukin 4
      (IL-4) reduces expression of all four on activated B cells at the level of
      messenger RNA and protein. This reduced expression is dependent on continuous
      exposure to IL-4 and is mediated through Stat6. Coligation of Fc gamma RII to the
      B cell receptor (BCR) via intact IgG increases the B cell activation threshold
      and suppresses antigen presentation. IL-4 completely abolishes these negative
      regulatory effects of Fc gamma RII. CD22 coligation with the BCR also suppresses
      activation -- this suppression too is abolished by IL-4. Thus, IL-4 is likely to
      enhance the B cell immune response by releasing B cells from inhibitory receptor
      suppression. By this coordinate reduction in expression of inhibitory receptors,
      and release from CD22 and Fc gamma RII-mediated inhibition, IL-4 is likely to
      play a role in T cell help of B cells and the development of T helper cell type 2
      responses. Conversely, B cell activation in the absence of IL-4 would be more
      difficult to achieve, contributing to the maintenance of B cell tolerance in the
      absence of T cell help.

PMID- 11956301
TI  - Promoter hypermethylation and post-transcriptional mechanisms for reduced BRCA1
      immunoreactivity in sporadic human breast cancers.
AB  - BACKGROUND: Germline mutation of BRCA1 is well known to cause familial breast
      cancer. Although somatic mutations of the BRCA1 gene are rare in sporadic breast
      cancers, a high incidence of reduced BRCA1 immunoreactivity has been
      demonstrated. As one of the mechanisms for this, gene silencing by
      hypermethylation of the BRCA1 promoter region has been reported. Here, we show
      the presence of a post-transcriptional mechanism by examining promoter
      hypermethylation, mRNA expression levels and immunoreactivity of BRCA1 in
      sporadic human breast cancers METHODS: Paired samples of 20 invasive ductal
      carcinomas and one invasive lobular carcinoma were obtained from sporadic breast
      cancer cases. The BRCA1 protein expression levels were determined by
      immunohistochemistry using a well-characterized antibody. The methylation status
      of the BRCA1 promoter region was determined by sequencing after bisulfite
      modification. The mRNA expression levels were determined by semi-quantitative
      reverse transcription polymerase chain reaction (PCR). Mutations in the entire
      BRCA1 coding region were analyzed by PCR single-strand conformation polymorphism
      analysis. RESULTS: Reduced immunoreactivity was observed in 13 of the 21 cancers.
      Hypermethylation was observed in five of the 13 cancers with reduced
      immunoreactivity and mRNA expression was almost absent in these five cancers. In
      the remaining eight cancers, mRNA expression was not decreased. None of the 21
      cancers examined harbored BRCA1 mutations. CONCLUSION: These findings showed that
      post-transcriptional mechanisms, such as low efficiency of translation or reduced
      stability of BRCA1 protein, are also involved in reduced BRCA1 immunoreactivity
      in sporadic breast cancers.

PMID- 11956302
TI  - Beta IGH3, a TGF-beta inducible gene, is overexpressed in lung cancer.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) is capable of affecting
      the proliferation of many cell types. beta IGH3, TGF-beta inducible gene, was
      originally isolated from lung adenocarcinoma cell line (A549). We have
      hypothesized that beta IGH3 mRNA levels could be predictors of the development
      and invasion of lung cancer. METHODS: The study included 71 lung cancer cases.
      The beta IGH3 mRNA levels were quantified by real time reverse transcription
      polymerase chain reaction (RT-PCR) using LightCycler. RESULTS: The beta IGH3 mRNA
      levels were elevated in tumor tissues from lung cancer (1.058 +/- 1.212) compared
      with non-malignant lung tissues (0.304 +/- 0.159) (p = 0.0001). No significant
      difference in beta IGH3 mRNA levels was found among gender, age, pathological
      subtype and lymph node metastasis. The beta IGH3 mRNA levels were elevated in
      tumor tissues from T4 lung cancer (1.425 +/- 1.470) compared with those from T1
      lung cancer (0.702 +/- 0.655) (p = 0.05) and T2 lung cancer (0.736 +/- 0.734) (p
      = 0.044). CONCLUSION: Using the LightCycler RT-PCR assay, the determination of
      beta IGH3 mRNA level might provide a potential marker for the aggressiveness of
      lung cancer. However, further studies and a longer follow-up are needed to
      confirm the impact of beta IGH3 on the biological behavior of the tumor.

PMID- 11956303
TI  - A phase II study of doxifluridine in elderly patients with advanced gastric
      cancer: the Japan Clinical Oncology Group Study (JCOG 9410).
AB  - BACKGROUND: A previous phase II study of doxifluridine in non-elderly patients
      with advanced gastric cancer demonstrated a favorable survival with mild
      toxicity, despite a low response rate. The objectives of this study were to
      evaluate efficacy and feasibility of this agent for elderly patients. METHODS:
      This study protocol required elderly patients, aged 76-80 years, with advanced
      gastric cancer and having no prior chemotherapy. Doxifluridine, at a dose of 1400
      mg/m(2)/day, was administered for four consecutive days followed by a 10-day
      rest. RESULTS: Between October 1994 and March 1998, 18 patients were registered.
      The study was then closed because of poor accrual. Toxicity was moderate; three
      patients suffered from grade 3 anemia and one patient each had grade 3
      thrombocytopenia, nausea/vomiting and grade 4 diarrhea. There was one partial
      response, seven with no change and 10 with progressive disease, yielding a
      response rate of 5.6%. The median progression-free survival and median survival
      time for the 18 patients were 55 and 164 days, respectively, with a 1-year
      survival rate of 5.6%. CONCLUSIONS: Although the number of patients was too small
      to draw any definitive conclusions, this study failed to demonstrate the survival
      advantage of doxifluridine.

PMID- 11956306
TI  - Long-term results of T1a, T1b and T1c invasive breast carcinomas in Japanese
      women: validation of the UICC T1 subgroup classification.
AB  - The objectives of this study were to investigate the long-term results of T1a,
      T1b and T1c Japanese invasive breast cancer patients defined by the UICC
      classification. The subjects were T1a (38), T1b (256) and T1c (1405) Japanese
      invasive breast cancer patients. Ten- and 20-year disease-free survival (DFS) and
      overall survival (OS) rates were analyzed by the UICC T1 subgroups (T1a, T1b,
      T1c). At 10 years, the respective DFS and OS rates of T1a, T1b and T1c patients
      were 91.9 and 91.9%, 86.1 and 86.8% and 82.4 and 83.9%, respectively. At 20
      years, the respective DFS and OS rates of T1a, T1b and T1c patients were 70.7 and
      70.7%, 76.7 and 76.7% and 69.1 and 70.1%. The differences of DFS and OS between
      T1a and T1c patients were not statistically significant. The DFS of patients with
      T1c breast carcinoma showed a statistically significant difference from that of
      T1b patients (p = 0.03). The validation of the T1 subgroup classification in
      Japanese breast cancer patients was confirmed, particularly for the T1c subgroup.

PMID- 11956304
TI  - Non-ischemic nephron-sparing surgery for small renal cell carcinoma: complete
      tumor enucleation using a microwave tissue coagulator.
AB  - OBJECTIVE: To determine the methodological usefulness of non-ischemic complete
      enucleation for small renal cell carcinomas (RCC) using a microwave tissue
      coagulator (MTC). METHODS: Fifty-nine patients (61 kidneys) underwent non
      ischemic complete tumor enucleation by MTC. Of the 59 patients, 46 had an
      elective indication and 15 kidneys of 13 patients had an imperative indication.
      RCC was exposed with minimal peri-renal detachment. The demarcation line, 7-10 mm
      from the tumor, was coagulated at 8-10 mm intervals with a microwave antenna
      needle for 30-40 s at 50-60 W. The renal tumor was excised along the coagulated
      zone with normal surrounding tissue. The enucleation bed was covered with fibrin
      glue or fat tissue without approximation. RESULTS: The operations were
      successfully completed in all intended cases. The mean operation time was 160 +/-
      43 (median: 160) min and the mean blood loss was 313 +/- 370 (median: 158) ml. No
      major bleeding or urine leakage from the enucleation bed was observed in 62.2 and
      88.5% of cases, respectively. The minor bleeding and urine leakage were
      controlled easily with absorbable sutures. None of the cases presented with
      postoperative bleeding or urine leakage from the enucleation bed. Severe
      impairment of the renal function was not observed in any case evaluated by means
      of serum creatinine, creatinine clearance and radioisotope examination. The 5
      year overall survival rate was 87% without recurrence up to 23.1 +/- 19.5 months
      of the mean follow-up. CONCLUSION: Non-ischemic complete tumor enucleation using
      MTC constitutes a simple, reliable and less invasive alternative to ordinary
      nephron-sparing surgeries for small RCC.

PMID- 11956308
TI  - Public advocacy of science. By Caveman.

PMID- 11956307
TI  - Microsatellite instability and immunohistochemical analysis of MLH1 and MSH2 in
      normal endometrium, endometrial hyperplasia and endometrial cancer from a
      hereditary nonpolyposis colorectal cancer patient.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC)-related endometrial cancer is
      associated with mutations in DNA mismatch repair genes. However, chronological
      changes of these genes in the endometrium have not been studied in women from
      HNPCC families. Tissue samples of normal endometrium, endometrial hyperplasia
      without atypia and endometrial cancer were collected at different times from a 41
      year-old Japanese woman with a family history of HNPCC. Combined microsatellite
      instability (MSI) and immunohistochemical analysis of MLH1 and MSH2 predicted the
      presence of a mutation in MSH2 when she had endometrial hyperplasia without
      atypia 7 months before the diagnosis of endometrial cancer. Endometrial
      hyperplasia without atypia may indicate an early development of endometrial
      cancer in women from HNPCC families.

PMID- 11956305
TI  - Comparison of the results of radical hysterectomy: sequential observations in
      each period.
AB  - BACKGROUND: The efficacy of drains and of antibiotics for prophylaxis of
      postoperative retroperitoneal infections following radical hysterectomy with
      systematic lymphadenectomy has not yet been adequately investigated. METHODS:
      Patients who had just undergone radical hysterectomy were divided into three
      groups. We used a retroperitoneal drain transvaginally for Groups A (n = 54) and
      B (n = 55) and transabdominally for Group C (n = 103). Group A was administered a
      first- and Groups B and C a second- or third-generation cephem antibiotic as the
      prophylactic antibiotic. We compared the surgery time, blood loss, fever index
      and febrile morbidity in these three groups. RESULTS: The average surgery time
      was Group A 344.2 +/- 13.7 min (mean +/- SE), Group B 425.6 +/- 11.0 min and
      Group C 528.2 +/- 10.9 min. A significant difference was observed among the
      groups (p < 0.05). In terms of blood loss during surgery, a significant increase
      (p < 0.05) occurred in Groups B (2400 +/- 196 g) and C (2373 +/- 130 g) compared
      with Group A (1820 +/- 122 g). For fever index, Group A showed a value of 36.1 +/
      2.7 dh, Group B 19.9 +/- 2.4 dh and Group C 8.8 +/- 1.5 dh. A significant
      difference was observed among the groups (p < 0.01). In terms of febrile
      morbidity, significant differences (p < 0.01, p < 0.0001) were observed between
      Groups B (14.6%) and C (8.7%) in comparison with Group A (44.4%), respectively.
      CONCLUSION: In radical hysterectomy with systematic lymphadenectomy, it may be
      preferable to choose transabdominal drains in the retroperitoneal space and
      second-generation cephem antibiotics for prophylaxis of postoperative
      retroperitoneal infections.

PMID- 11956309
TI  - A journey through the exocytic pathway.

PMID- 11956311
TI  - Role of Grb2 in EGF-stimulated EGFR internalization.
AB  - Grb2 is an adaptor molecule that couples membrane receptors such as the epidermal
      growth factor receptor (EGFR) to intracellular signaling pathways. To gain
      insight into the trafficking pathways followed by these molecules after
      activation by EGF, we visualized Grb2 and EGFR fused to GFP spectral variants in
      single live cells. In nonstimulated cells, Grb2-YFP was primarily localized
      diffusely in the cytoplasm, whereas EGFR-CFP was found on the plasma membrane and
      in endocytic structures localized in the perinuclear area. Within 1 minute of EGF
      stimulation, Grb2 redistributed to the plasma membrane where it bound EGFR-CFP in
      an SH2 dependent manner. The plasma membrane then began to dynamically ruffle,
      and Grb2-YFP and EGFR-CFP were found to internalize together in large
      macropinocytic structures. These structures were morphologically distinct from
      conventional, clathrin-derived endosomes and did not label with transferrin, AP-2
      or clathrin heavy chain. Evidence that these structures did not require clathrin
      for internalization came from experiments showing that expression of the C
      terminus of AP-180, which inhibited transferrin uptake, had no effect on EGF
      induced internalization of EGFR. YFP-tagged Grb2 containing an inhibitory
      mutation in either N- or C-SH3 domain redistributed to the plasma membrane upon
      EGF stimulation, but the macropinocytic structures containing Grb2-YFP and EGFR
      CFP did not translocate inward and appeared to remain tethered to the plasma
      membrane. This suggested that the Grb2 SH3 domain was responsible for coupling
      the membranes containing EGFR with downstream effectors involved in
      internalization of these membranes. Transferrin uptake was unaffected in the
      presence of all of the SH3 domain mutants, consistent with the EGF-stimulated
      EGFR internalization pathway being clathrin-independent. These results
      demonstrate a role for Grb2 in events associated with a macropinocytic
      internalization pathway for EGFR in activated cells.

PMID- 11956310
TI  - Stem cells of the oesophageal epithelium.
AB  - Cancers arising in the oesophageal epithelium are among the most common fatal
      tumors in the world. Despite this, comparatively little is known about the cell
      biology and organization of this tissue. Recently, in vitro and in vivo
      techniques developed over the past 30 years for the study of the epidermis have
      been applied to the study of the oesophageal epithelium. This approach, combined
      with data from previous histochemical studies, has lead to the identification and
      isolation of putative oesophageal epithelial stem cells. Oesophageal epithelial
      stem cells demonstrate several unusual properties, and their identification may
      facilitate studies on oesophageal carcinogenesis.

PMID- 11956312
TI  - Loss of heterochromatin protein 1 (HP1) chromodomain function in mammalian cells
      by intracellular antibodies causes cell death.
AB  - The chromodomain (CD) is a highly conserved motif present in a variety of animal
      and plant proteins, and its probable role is to assemble a variety of
      macromolecular complexes in chromatin. The importance of the CD to the survival
      of mammalian cells has been tested. Accordingly, we have ablated CD function
      using two single-chain intracellular Fv (scFv) fragments directed against non
      overlapping epitopes within the HP1 CD motif. The scFv fragments can recognize
      both CD motifs of HP1 and Polycomb (Pc) in vitro and, when expressed
      intracellularly, interact with and dislodge the HP1 protein(s) from their
      heterochromatin localization in vivo. Mouse and human fibroblasts expressing anti
      chromodomain scFv fragments show a cell-lethal phenotype and an apoptotic
      morphology becomes apparent soon after transfection. The mechanism of cell death
      appears to be p53 independent, and the cells are only partly rescued by
      incubation with the wide spectrum caspase inhibitor Z-VAD fmk. We conclude that
      expression of anti-chromodomain intracellular antibodies is sufficient to trigger
      a p53-independent apoptotic pathway that is only partly dependent on the known Z
      VAD-inhibitable caspases, suggesting that CD function is essential for cell
      survival.

PMID- 11956313
TI  - Direct binding of NuMA to tubulin is mediated by a novel sequence motif in the
      tail domain that bundles and stabilizes microtubules.
AB  - In mitosis, NuMA localises to spindle poles where it contributes to the formation
      and maintenance of focussed microtubule arrays. Previous work has shown that NuMA
      is transported to the poles by dynein and dynactin. So far, it is unclear how
      NuMA accumulates at the spindle poles following transport and how it remains
      associated throughout mitosis. We show here that NuMA can bind to microtubules
      independently of dynein/dynactin. We characterise a 100-residue domain located
      within the C-terminal tail of NuMA that mediates a direct interaction with
      tubulin in vitro and that is necessary for NuMA association with tubulin in vivo.
      Moreover, this domain induces bundling and stabilisation of microtubules when
      expressed in cultured cells and leads to formation of abnormal mitotic spindles
      with increased microtubule asters or multiple poles. Our results suggest that
      NuMA organises the poles by stable crosslinking of the microtubule fibers.

PMID- 11956314
TI  - CEP110 and ninein are located in a specific domain of the centrosome associated
      with centrosome maturation.
AB  - The mammalian centrosome consists of a pair of centrioles surrounded by
      pericentriolar material (PCM). The architecture and composition of the
      centrosome, especially the PCM, changes during the cell cycle. Recently, a subset
      of PCM proteins have been shown to be arranged in a tubular conformation with an
      open and a closed end within the centrosome. The presence of such a specific
      configuration can be used as a landmark for mapping proteins in both a spatial
      and a temporal fashion. Such mapping studies can provide information about
      centrosome organization, protein dynamics, protein-protein interactions as well
      as protein function. In this study, the centrosomal proteins CEP110 and ninein
      were mapped in relationship to the tubular configuration. Both proteins were
      found to exhibit a similar distribution pattern. In the mother centrosome, they
      were found at both ends of the centrosome tube, including the site of centrosome
      duplication. However, in the daughter centrosome they were present only at the
      closed end. At the closed end of the mother and daughter centrosome tube, both
      CEP110 and ninein co-localized with the centriolar protein CEP250/c-Nap1, which
      confirms ninein's centriole association and places CEP110 in association with
      this structure. Importantly, the appearance of CEP110 and ninein at the open end
      of the daughter centrosome occurred during the telophase-G1 transition of the
      next cell cycle, concomitant with the maturation of the daughter centrosome into
      a mother centrosome. Microinjection of antibodies against either CEP110 or ninein
      into metaphase HeLa cells disrupted the reformation of the tubular conformation
      of proteins within the centrosome following cell division and consequently led to
      dispersal of centrosomal material throughout the cytosol. Further, microinjection
      of antibodies to either CEP110 or ninein into metaphase PtK2 cells not only
      disrupted the tubular configuration within the centrosome but also affected the
      centrosome's ability to function as a microtubule organizing center (MTOC). This
      MTOC function was also disrupted when the antibodies were injected into
      postmitotic cells. Taken together, our results indicate that: (1) a population of
      CEP110 and ninein is located in a specific domain within the centrosome, which
      corresponds to the open end of the centrosome tube and is the site of protein
      addition associated with maturation of a daughter centrosome into a mother
      centrosome; and (2) the addition of CEP110 and ninein are essential for the
      reformation of specific aspects of the interphase centrosome architecture
      following mitosis as well as being required for the centrosome to function as a
      MTOC.

PMID- 11956315
TI  - Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary
      human endothelial cells.
AB  - The integrity of the endothelium is dependent on cell-cell adhesion, which is
      mediated by vascular-endothelial (VE)-cadherin. Proper VE-cadherin-mediated
      homotypic adhesion is, in turn, dependent on the connection between VE-cadherin
      and the cortical actin cytoskeleton. Rho-like small GTPases are key molecular
      switches that control cytoskeletal dynamics and cadherin function in epithelial
      as well as endothelial cells. We show here that a cell-penetrating,
      constitutively active form of Rac (Tat-RacV12) induces a rapid loss of VE
      cadherin-mediated cell-cell adhesion in endothelial cells from primary human
      umbilical veins (pHUVEC). This effect is accompanied by the formation of actin
      stress fibers and is dependent on Rho activity. However, transduction of pHUVEC
      with Tat-RhoV14, which induces pronounced stress fiber and focal adhesion
      formation, did not result in a redistribution of VE-cadherin or an overall loss
      of cell-cell adhesion. In line with this observation, endothelial permeability
      was more efficiently increased by Tat-RacV12 than by Tat-RhoV14. The loss of cell
      cell adhesion, which is induced by Tat-RacV12, occurred in parallel to and was
      dependent upon the intracellular production of reactive oxygen species (ROS).
      Moreover, Tat-RacV12 induced an increase in tyrosine phosphorylation of a
      component the VE-cadherin-catenin complex, which was identified as alpha-catenin.
      The functional relevance of this signaling pathway was further underscored by the
      observation that endothelial cell migration, which requires a transient reduction
      of cell-cell adhesion, was blocked when signaling through ROS was inhibited. In
      conclusion, Rac-mediated production of ROS represents a previously unrecognized
      means of regulating VE-cadherin function and may play an important role in the
      (patho)physiology associated with inflammation and endothelial damage as well as
      with endothelial cell migration and angiogenesis.

PMID- 11956316
TI  - The novel HECT-type ubiquitin-protein ligase Pub2p shares partially overlapping
      function with Pub1p in Schizosaccharomyces pombe.
AB  - The fission yeast Schizosaccharomyces pombe has three putative ubiquitin-protein
      ligases of the Nedd4/Rsp5 family, named Pub1p, Pub2p and Pub3p. Pub1p has been
      reported to be involved in cell cycle regulation and proliferation under acidic
      pH conditions. Here we characterize Pub2p, which contains a conserved HECT domain
      and a WW domain but lacks a C2 domain. Transcription of the pub2(+) gene was
      constitutive and further enhanced by nitrogen starvation. A pub2-null mutation
      gave no remarkable phenotypes, but intensified temperature sensitivity in a
      pub1Delta background. Moderately overexpressed pub2(+) suppressed the temperature
      sensitivity of pub1Delta cells, which suggests that the function of Pub2p
      overlaps with that of Pub1p. Overexpression of pub2(+) by a strong nmt1 promoter
      in wild-type strains caused growth arrest and cell elongation, probably owing to
      defects in G2 progression or the G2/M transition. Unlike Pub1p, however,
      overexpression of Pub2p did not reduce the levels of Cdc25p. Pub2-GFP was found
      throughout the cell, especially at the cell surface in the polar regions. Pub2p
      contains a conserved cysteine residue (Cys639) in its putative catalytic HECT
      domain that can be thiol-ubiquitinated. Substitution of Cys639 by alanine
      (Pub2CA) caused a functional defect, because growth arrest and cell elongation
      were not induced by overexpression of Pub2CA. A chimeric Pub1 protein, in which
      the HECT domain was replaced by the Pub2 HECT domain, completely suppressed the
      temperature sensitivity of pub1Delta cells, suggesting that the HECT domain of
      Pub2p has the catalytic activity of a ubiquitin ligase. We conclude that Pub2p is
      a HECT-type ubiquitin-protein ligase that shares partially overlapping function
      with Pub1p.

PMID- 11956317
TI  - The Drosophila gap junction channel gene innexin 2 controls foregut development
      in response to Wingless signalling.
AB  - In invertebrates, the direct communication of neighbouring cells is mediated by
      gap junctions, which are composed of oligomers of the innexin family of
      transmembrane proteins. Studies of the few known innexin mutants in Drosophila
      and C. elegans have shown that innexin proteins, which are structurally analogous
      to the connexins in vertebrates, play a major structural role as gap junctional
      core components in electric signal transmission. We show that Drosophila innexin
      2 mutants display a feeding defect that originates from a failure of epithelial
      cells to migrate and invaginate during proventriculus organogenesis. The
      proventriculus is a valve-like organ that regulates food passage from the foregut
      into the midgut. Immunohistological studies indicate that innexin 2 is
      functionally required to establish a primordial structure of the proventriculus,
      the keyhole, during the regionalisation of the embryonic foregut tube, which is
      under the control of Wingless and Hedgehog signalling. Our genetic lack- and gain
      of-function studies, and experiments in Dorsophila tissue culture cells provide
      strong evidence that innexin 2 is a target gene of Wingless signalling in the
      proventricular cells. This is the first evidence, to our knowledge, that an
      invertebrate gap junction gene controls epithelial tissue and organ morphogenesis
      in response to the conserved WNT signalling cascade.

PMID- 11956318
TI  - Calcium signalling in tissue: diversity and domain-specific integration of
      individual cell response in salivary glands.
AB  - Organ function requires coordinated multicellular activities, which may require
      proper control of cell signalling dynamics at the supracellular level. By using
      high-speed confocal microscopy, we studied how calcium signalling is organised in
      the dissociated rat parotid gland. Salivary gland function is accomplished
      primarily by the compartmentalized epithelial domains, acini and ducts, the
      former involved in the production of primary saliva and the latter involved in
      its modification. Upon muscarinic stimulation with carbachol, both domains showed
      an increase in intracellular free calcium concentration ([Ca(2+)]i) with
      distinctive spatiotemporal kinetics, as indicated by the fluo-3 fluorescence.
      Acini responded initially, and the ducts followed with a time lag of more than
      0.3 second. Cells comprising an acinus responded synchronously, whereas those in
      the ducts responded heterogeneously with respect to the latency period, magnitude
      of response and the requirement of extracellular calcium to raise [Ca(2+)]i. ATP
      also elicited a non-synchronous [Ca(2+)]i response in the duct domain, under a
      pattern different from that of carbachol. The synchronous oscillations seen in
      the acinar domain were made asynchronous by octanol, an agent known to inhibit
      gap-junction function. Accordingly, a gap junction component, connexin 32, was
      immunolocalised predominantly between the acinar cells. Moreover, expression of
      the type 2 inositol (1,4,5)-trisphosphate receptor [Ins(1,4,5)P(3)R] was
      homogeneous in the acinar domain but heterogeneous in the duct domain. Together,
      these data suggest that the calcium signalling system in salivary glands is
      constructed specifically according to the tissue architecture.

PMID- 11956319
TI  - Visualisation of the actin cytoskeleton by cryo-electron microscopy.
AB  - An understanding of the mechanisms driving cell motility requires clarification
      of the structural organisation of actin filament arrays in the regions of cell
      protrusion termed lamellipodia. Currently, there is a lack of consensus on
      lamellipodia organisation stemming from the application of alternative procedures
      for ultrastructural visualisation of cytoskeleton networks. In this study, we
      show that cryo-electron microscopy of extracted cytoskeletons embedded in a thin
      layer of vitreous ice can reveal the organisation of cytoskeletal elements at
      high resolution. Since this method involves no dehydration, drying and
      contrasting steps that can potentially introduce subtle distortions of filament
      order and interactions, its application opens the way to resolving the
      controversial details of lamellipodia architecture.

PMID- 11956320
TI  - Leukotriene D(4) activates MAPK through a Ras-independent but PKCepsilon
      dependent pathway in intestinal epithelial cells.
AB  - We have recently shown that leukotriene D(4) (LTD(4)) increases cell survival in
      intestinal epithelial cells. Here we report and explore the complementary finding
      that LTD(4) also enhances proliferation in these cells. This proliferative
      response was approximately half of that induced by epidermal growth factor (EGF)
      and its required activation of protein kinase C (PKC), Ras and the mitogen
      activated protein kinase (MAPK) Erk-1/2. EGF also activated Erk-1/2 in these
      cells; however the EGF-receptor inhibitor PD153035 did not affect the LTD(4)
      induced activation of Erk-1/2. In addition, LTD(4) did not induce phosphorylation
      of the EGF receptor, nor did pertussis toxin (PTX) block EGF-induced activation
      of Erk-1/2, thus refuting a possible crosstalk between the receptors.
      Furthermore, LTD(4)-induced, but not EGF-induced, activation of Erk-1/2 was
      sensitive to PTX, PKC inhibitors and downregulation of PKCepsilon. A definite
      role for PKCepsilon in LTD(4)-induced stimulation of Erk-1/2 was documented by
      the inability of LTD(4) to activate Erk-1/2 in cells transfected with either the
      regulatory domain of PKCepsilon (an isoform specific dominant-negative inhibitor)
      or a kinase-dead PKCepsilon. Although Ras and Raf-1 were both transiently
      activated by LTD(4), only Raf-1 activation was abolished by abrogation of the PKC
      signal. Furthermore, the LTD(4)-induced activation of Erk-1/2 was unaffected by
      transfection with dominant-negative N17 Ras but blocked by transfection with
      kinase-dead Raf-1. Consequently, LTD(4) regulates the proliferative response by a
      distinct Ras-independent, PKCepsilon-dependent activation of Erk-1/2 and a
      parallel Ras-dependent signaling pathway.

PMID- 11956322
TI  - Altered expression of the 100 kDa subunit of the Dictyostelium vacuolar proton
      pump impairs enzyme assembly, endocytic function and cytosolic pH regulation.
AB  - The vacuolar proton pump (V-ATPase) appears to be essential for viability of
      Dictyostelium cells. To investigate the function of VatM, the 100 kDa
      transmembrane V-ATPase subunit, we altered its level. By means of homologous
      recombination, the promoter for the chromosomal vatM gene was replaced with the
      promoter for the act6 gene, yielding the mutant strain VatMpr. The act6 promoter
      is much more active in cells growing axenically than on bacteria. Thus,
      transformants were selected under axenic growth conditions, then shifted to
      bacteria to determine the consequences of reduced vatM expression. When VatMpr
      cells were grown on bacteria, the level of the 100 kDa V-ATPase subunit dropped,
      cell growth slowed, and the A subunit, a component of the peripheral catalytic
      domain of the V-ATPase, became mislocalized. These defects were complemented by
      transformation of the mutant cells with a plasmid expressing vatM under the
      control of its own promoter. Although the principal locus of vacuolar proton
      pumps in Dictyostelium is membranes of the contractile vacuole system, mutant
      cells did not manifest osmoregulatory defects. However, bacterially grown VatMpr
      cells did exhibit substantially reduced rates of phagocytosis and a prolonged
      endosomal transit time. In addition, mutant cells manifested alterations in the
      dynamic regulation of cytosolic pH that are characteristic of normal cells grown
      in acid media, which suggested that the V-ATPase also plays a role in cytosolic
      pH regulation.

PMID- 11956323
TI  - DdNek2, the first non-vertebrate homologue of human Nek2, is involved in the
      formation of microtubule-organizing centers.
AB  - Dictyostelium Nek2 (DdNek2) is the first structural and functional non-vertebrate
      homologue of human Nek2, a NIMA-related serine/threonine kinase required for
      centrosome splitting in early mitosis. DdNek2 shares 43% overall amino-acid
      identity with its human counterpart and 54% identity within the catalytic domain.
      Both proteins can be subdivided in an N-terminal catalytic domain, a leucine
      zipper and a C-terminal domain. Kinase assays with bacterially expressed DdNek2
      and C-terminal deletion mutants revealed that catalytic activity requires the
      presence of the leucine zipper and that autophosphorylation occurs at the C
      terminus. Microscopic analyses with DdNek2 antibodies and expression of a GFP
      DdNek2 fusion protein in Dictyostelium showed that DdNek2 is a permanent
      centrosomal resident and suggested that it is a component of the centrosomal
      core. The GFP-DdNek2-overexpressing mutants frequently exhibit supernumerary
      microtubule-organizing centers (MTOCs). This phenotype did not require catalytic
      activity because it was also observed in cells expressing inactive GFP-K33R.
      However, it was shown to be caused by overexpression of the C-terminal domain
      since it also occurred in GFP-mutants expressing only the C-terminus or a leucine
      zipper/C-terminus construct but not in those mutants expressing only the
      catalytic domain or a catalytic domain/leucine zipper construct. These results
      suggest that DdNek2 is involved in the formation of MTOCs. Furthermore, the
      localization of the GFP-fusion proteins revealed two independent centrosomal
      targeting domains of DdNek2, one within the catalytic or leucine zipper domain
      and one in the C-terminal domain.

PMID- 11956321
TI  - Characterization of rat TOM70 as a receptor of the preprotein translocase of the
      mitochondrial outer membrane.
AB  - We cloned a approximately 70 kDa rat mitochondrial outer membrane protein (OM70)
      with a sequence identity of 28.1% and 20.1% with N. crassa and S. cerevisiae
      Tom70, respectively. Even with this low sequence identity, however, the proteins
      share a remarkable structural similarity: they have 7-10 tetratricopeptide repeat
      motifs and are anchored to the outer membrane through the N-terminal
      transmembrane domain with the bulk portion located in the cytosol. Antibodies
      against OM70 inhibited import of preproteins, such as the ADP/ATP carrier and
      rTOM40, that use internal targeting signals but not the import of cleavable
      presequence-containing preproteins. Blue native gel electrophoresis and
      immunoprecipitation of digitoninsolubilized mitochondrial outer membranes
      revealed that OM70 was loosely associated with the approximately 400 kDa
      translocase complex of the mitochondrial outer membrane, which contains rTOM22
      and rTOM40. A yeast two-hybrid system demonstrated that OM70 interacted with
      rTOM20 and rTOM22 through the cytoplasmic domains. Thus, OM70 is a functional
      homologue of fungal Tom70 and functions as a receptor of the preprotein import
      machinery of the rat mitochondrial outer membrane. Furthermore, the N-terminal 66
      residue region of OM70, which comprises a hydrophilic 41 residue N-terminal
      domain, a 22 residue transmembrane domain and three arginine residues, is
      sufficient to act as a mitochondria-targeting signal, and the arginine cluster is
      crucial for this function.

PMID- 11956324
TI  - Interaction of mitochondria with microtubules in the filamentous fungus
      Neurospora crassa.
AB  - The establishment and maintenance of the 3D structure of eukaryotic cells depends
      on active transport and positioning of organelles along cytoskeletal elements.
      The biochemical basis of these processes is only poorly understood. We analysed
      the interaction of mitochondria with microtubules in the filamentous fungus
      Neurospora crassa. Mitochondria were fluorescently labelled by expression of
      matrix-targeted green fluorescent protein. Upon isolation, mitochondria collapsed
      to round spherical structures that were still able to interact with microtubules
      in vitro. Binding of mitochondria to microtubules was dependent on peripherally
      associated proteins on the organellar surface, and was sensitive to adenine
      nucleotides. MMM1, a mitochondrial outer membrane protein important for
      maintenance of normal mitochondrial morphology, was not required. This suggests
      that the interaction of mitochondria with the cytoskeleton is independent of
      MMM1. We conclude that mitochondrial morphology is maintained by a complex
      interplay of extrinsic and intrinsic factors, including ATP-dependent proteins on
      the organellar surface.

PMID- 11956325
TI  - Formation of Hirano bodies in Dictyostelium and mammalian cells induced by
      expression of a modified form of an actin-crosslinking protein.
AB  - We report the serendipitous development of the first cultured cell models of
      Hirano bodies. Myc-epitope-tagged forms of the 34 kDa actin bundling protein
      (amino acids 1-295) and the CT fragment (amino acids 124-295) of the 34 kDa
      protein that exhibits activated actin binding and calcium-insensitive actin
      filament crosslinking activity were expressed in Dictyostelium and mammalian
      cells to assess the behavior of these modified forms in vivo. Dictyostelium cells
      expressing the CT-myc fragment: (1) form ellipsoidal regions that contain ordered
      assemblies of F-actin, CT-myc, myosin II, cofilin and alpha-actinin; (2) grow and
      develop more slowly than wildtype, but produce normal morphogenetic structures;
      (3) perform pinocytosis and phagocytosis normally; and (4) produce a level of
      total actin equivalent to wildtype, but a higher level of F-actin. The
      paracrystalline inclusions bear a striking resemblance to Hirano bodies, which
      are associated with a number of pathological conditions. Furthermore, expression
      of the CT fragment in murine L cells results in F-actin rearrangements
      characterized by loss of stress fibers, accumulation of numerous punctate foci,
      and large perinuclear aggregates, the Hirano bodies. Thus, failure to regulate
      the activity and/or affinity of an actin crosslinking protein can provide a
      signal for formation of Hirano bodies. More generally, formation of Hirano bodies
      is a cellular response to or a consequence of aberrant function of the actin
      cytoskeleton. The results reveal that formation of Hirano bodies is not
      necessarily related to cell death. These cultured cell models should facilitate
      studies of the biochemistry, genetics and physiological effects of Hirano bodies.

PMID- 11956326
TI  - Increased responsiveness of hypoxic endothelial cells to FGF2 is mediated by HIF
      1alpha-dependent regulation of enzymes involved in synthesis of heparan sulfate
      FGF2-binding sites.
AB  - Binding of basic fibroblast growth factor (FGF2) to its high affinity receptors
      requires the presence of specific heparan sulfate (HS) moieties on the cell
      surface that act as coreceptors. To determine the contribution of cell-surface HS
      to modulation of FGF2-dependent cell growth, we studied the changes in the cell
      mass and FGF2 binding of endothelial cell HS under normoxic and hypoxic
      conditions in vitro. Both large vein and cardiac microvascular endothelial cells
      cultured under hypoxic conditions demonstrated an increase in the ratio of cell
      surface HS to chondroitin sulfate (CS), as well as an increase in the number of
      low affinity (HS-associated) binding sites for FGF2 with no change in the
      apparent K(d). This increase in the number of HS-FGF2 binding sites, in the
      absence of a significant change in FGF receptor expression, resulted in enhanced
      responsiveness of hypoxic, compared with normoxic, endothelial cells to FGF2
      stimulation. Gene expression studies demonstrated increased expression of the key
      regulatory enzyme responsible for HS chain synthesis, 1,4 GlcNAc transferase
      (GlcNAcT-I), as well as increased expression of 2-O sulfotransferase (HS2ST), the
      enzyme responsible for sulfation of IdoA, a crucial part of the HS-FGF2 binding
      site. Transduction of cells with an adenovirus encoding a HIF-1alpha expression
      construct resulted in a similar increase in GlcNAcT-I and HS2ST expression. We
      conclude that hypoxia increases endothelial cell responsiveness to FGF2 by
      promoting preferential synthesis of HS rather than CS chains and increasing the
      number of FGF2-binding sites on HS chains. Both of these events are mediated by a
      HIF-1alpha-dependent increase in expression of the enzymes GlnNAcT-I and HS2ST.
      This shift in cell-surface HS composition results in enhanced cell sensitivity to
      FGF2-induced growth stimulation.

PMID- 11956327
TI  - The catalytic domain of endogenous urokinase-type plasminogen activator is
      required for the mitogenic activity of platelet-derived and basic fibroblast
      growth factors in human vascular smooth muscle cells.
AB  - Emerging data suggest that urokinase-type plasminogen activator (UPA), beyond its
      role in pericellular proteolysis, may also act as a mitogen. We investigated the
      function of endogenous UPA in mediating the mitogenic effects of platelet-derived
      growth factor (PDGF) and basic fibroblast growth factor (bFGF) on human vascular
      smooth muscle cells (SMC). Growth-arrested SMC constitutively expressed UPA, but
      UPA expression and secretion increased several times upon stimulation with either
      PDGF or bFGF. Inhibition of endogenous UPA with a polyclonal antibody
      significantly reduced DNA synthesis and proliferation of PDGF or bFGF stimulated
      SMC, this effect already being evident when the cells entered S-phase. The
      proliferative activity of endogenous UPA was dependent on a functional catalytic
      domain as demonstrated by inhibition experiments with a specific monoclonal
      antibody (394OA) and p-aminobenzamidine, respectively. In contrast, neither
      plasmin generation nor binding of UPA to its receptor (CD87) were required for
      UPA-mediated mitogenic effects. The results demonstrate that endogenous UPA is
      not only overexpressed in SMC upon stimulation with PDGF/bFGF, but also mediates
      the mitogenic activity of the growth factors in a catalytic-domain-dependent
      manner. Specific inhibition of this UPA domain may represent an attractive target
      for pharmacological interventions in atherogenesis and restenosis after
      angioplasty.

PMID- 11956328
TI  - Ca(2+)-binding proteins of cilia and infraciliary lattice of Paramecium
      tetraurelia: their phosphorylation by purified endogenous Ca(2+)-dependent
      protein kinases.
AB  - We purified two small, acidic calcium-binding proteins (Paramecium Ca(2+)-binding
      proteins, PCBP-25alpha and PCBP-25beta) from Paramecium tetraurelia by Ca(2+)
      dependent chromatography on phenyl-Sepharose and by anion-exchange
      chromatography. The proteins were immunologically distinct. Monoclonal antibodies
      against PCBP-25beta did not react with PCBP-25alpha, and antibodies against
      centrin from Chlamydomonas reacted with PCBP-25alpha but not with PCBP-25beta.
      Like the centrins described previously, both PCBPs were associated with the
      infraciliary lattice (ICL), a fibrillar cytoskeletal element in Paramecium. Both
      were also present in isolated cilia, from which they could be released (with
      dynein) by a high-salt wash, and both PCBPs cosedimented with dynein in a sucrose
      gradient. PCBP-25beta was especially prominent in cilia and in the deciliation
      supernatant, a soluble fraction released during the process of deciliation. The
      results of immunoreactivity and localization experiments suggest that PCBP
      25alpha is a Paramecium centrin and that PCBP-25beta is a distinct Ca(2+)-binding
      protein that confers Ca(2+) sensitivity on some component of the cilium, ciliary
      basal body or ICL. We characterized these proteins and Paramecium calmodulin as
      substrates for two Ca(2+)-dependent protein kinases purified from Paramecium.
      PCBP-25alpha and calmodulin were in vitro substrates for one of the two Ca(2+)
      dependent protein kinases (CaPK-2), but only PCBP-25alpha was phosphorylated by
      CaPK-1. These results raise the possibility that the biological activities of
      PCBP-25alpha and calmodulin are regulated by phosphorylation.

PMID- 11956329
TI  - Activation of SGK1 by HGF, Rac1 and integrin-mediated cell adhesion in MDCK
      cells: PI-3K-dependent and -independent pathways.
AB  - The SGK1 protein belongs to the AGC gene family of kinases that are regulated by
      phosphorylation mediated by PDK1. SGK1 regulation is accomplished by several
      pathways including growth-factor and stress-mediated signaling. We have expanded
      the analysis of SGK1 regulation in epithelial cells. We used HA-tagged SGK1 to
      transiently transfect MDCK cells and study the regulation of SGK1 upon
      stimulation with HGF, cAMP or upon adhesion of the cells to immobilized
      fibronectin. In addition, we studied the regulation of SGK1 activity by small GTP
      binding proteins of the Rho family. Treatment of MDCK cells with HGF leads to a
      time-dependent activation of SGK1 that is blocked by wortmanin. This activation
      requires the conserved phosphorylation site present in the activation loop of the
      kinase (T256 in SGK1) and the phosphorylation site present in a hydrophobic
      domain at its C-terminus (S422 in SGK1), which are targets for PDK1/PDK2-mediated
      regulation of SGK1. We tested whether SGK1 could be activated by cAMP as it
      contains a putative PKA site. We were unable to demonstrate a significant
      activation of HA-SGK1 by cAMP stimulation under conditions where we detect cAMP
      mediated phosphorylation of the transcription factor CREB. Cotransfection of SGK1
      with activated small GTP-binding proteins revealed that Rac1, but not Rho or
      Rap1, induces activation of SGK1. However, this activation was wortmanin
      insensitive and dominant-negative Rac1 did not inhibit the HGF-mediated
      activation of SGK1. Adhesion of MDCK cells to immobilized fibronectin also leads
      to activation of SGK1. However, it appears that the integrin-mediated activation
      of HA-SGK1 differs from AKT activation in the fact that AKT phosphorylation was
      blocked by wortmanin (or LY294002) whereas HA-SGK1 was not. The adhesion
      dependent activation, however, requires the intact phosphorylation sites of SGK1.
      Co-transfection of HA-SGK1 with RacV12 results in increased activity in adherent
      cells compared with HA-SGK1 alone. Since RacN17 failed to inhibit adhesion
      dependent-activation of SGK1, it suggests that integrin activation is achieved by
      a parallel Rac-independent pathway. The activation of SGK1 by HGF and integrin
      provides a link between HGF-mediated protection of MDCK from de-attachment
      induced apoptosis (anoikis). We demonstrate that dephosphorylation of the
      transcription factor FKRHL1 induced by cell de-attachment is prevented by
      activated SGK1, suggesting that SGK1 regulates cell survival pathways. In
      summary, we demonstrate that SGK1 activation could be achieved through signaling
      pathways involved in the regulation of cell survival, cell-cell and cell-matrix
      interactions. SGK1 activation can be accomplished via HGF, PI-3K-dependent
      pathways and by integrin-mediated, PI-3K independent pathways. In addition,
      activation of SGK1 by the small GTP-binding protein Rac1 has been observed.

PMID- 11956331
TI  - Charge movement and transcription regulation of L-type calcium channel alpha(1S)
      in skeletal muscle cells.
AB  - Several factors, such as Ca(2+), trophic factors and ageing, regulate
      dihydropyridine-sensitive receptor (DHPR) alpha(1) subunit expression. However,
      basic mechanisms of DHPR alpha(1S) expression are unknown. To better understand
      the regulatory elements that control transcription, the 1.2 kb 5'-flanking region
      fragment immediately upstream of the mouse L-type Ca(2+) channel or DHPR
      alpha(1S) gene was isolated and sequenced. Luciferase reporter constructs driven
      by different promoter regions of mouse DHPR alpha(1S) gene were used for
      transient transfection assays in muscle C2C12 cells. In these preparations we
      found that three regions corresponding to CREB, GATA-2 and SOX-5 consensus
      sequence within the 5'-flanking region of the DHPR alpha(1S) gene are important
      for DHPR alpha(1S) gene transcription. Antisense oligonucleotides against CREB,
      GATA-2 and SOX-5 significantly reduced charge movement in C2C12 cells. Charge
      movement was recorded in the whole-cell configuration of the patch clamp
      technique. Results from cells transfected with antisense (AS) and sense (S)
      oligonucleotides and nontransfected cells were compared. Charge movement
      experiments were fitted to a Boltzmann equation. Maximum charge movement (Q(max))
      (nC microF(-1), mean +/- S.E.M.) for S- and AS-CREB was 70.3 +/- 2.9 and 52.8 +/-
      3.3, respectively (P < 0.05). The same parameter for S- and AS-GATA-2 was 71.3 +/
      3.9 and 48.2 +/- 2.3, respectively (P < 0.05) and for S- and AS-SOX-5 was 70.4
      +/- 4.2 and 45.1 +/- 3.2, respectively (P < 0.05). Values recorded in cells
      transfected with sense S-CREB, S-GATA-2 and S-SOX-5 oligonucleotides were not
      significantly different from those recorded in nontransfected cells. This study
      demonstrates that the transcription factors CREB, GATA-2 and SOX-5 play a
      significant role in the expression of the skeletal muscle DHPR or L-type Ca(2+)
      channel alpha(1S).

PMID- 11956332
TI  - NO donors potentiate the beta-adrenergic stimulation of I(Ca,L) and the
      muscarinic activation of I(K,ACh) in rat cardiac myocytes.
AB  - The effects of nitric oxide (NO) donors on the L-type Ca(2+) current (I(Ca,L))
      and the muscarinic activated K(+) current (I(K,ACh)) were studied in isolated rat
      cardiac myocytes. The nitrosothiol S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1
      pM-1 microM) strongly potentiated the stimulation of the I(Ca,L) elicited by
      subthreshold concentrations of isoprenaline (Iso, 0.1-0.5 nM) in ventricular
      myocytes. The effect of SNAP was mimicked by 2-(N,N-diethylamino)-diazenolate-2
      oxide (DEANO, 1 pM-1 nM), a NONOate that spontaneously releases NO in a pH
      controlled manner, and was blunted by 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide (100 microM), a NO trap. 1H
      [1,2,4]Oxadiazolo[4,3-a]quinoxaline-1-one (10 microM), a guanylyl cyclase
      inhibitor, did not alter the effect of SNAP. SNAP (1 pM-1 microM) did not modify
      the effect of L858051 (0.1-0.3 microM), a forskolin analogue that activates
      adenylyl cyclase, on I(Ca,L) and did not enhance the basal I(Ca,L) in the
      presence of rolipram (1 microM), a phosphodiesterase type 4 inhibitor.
      Superfusion with Rp-CPT-cAMPS (500 microM), or internal dialysis with cAMP
      dependent protein kinase (cA-PK) inhibitory peptide (PKI; 20 microM), inhibitors
      of the cA-PK, blunted the effect of SNAP (1 nM and 1 microM) on the Iso
      stimulated (1-100 pM) I(Ca,L). SNAP (1 nM and 1 microM) potentiated the threshold
      stimulation of I(Ca,L) elicited by internal GTP-gammaS (10 microM), a non
      hydrolysable analogue of GTP. SNAP (1 pM-1 microM) and DEANO (1 microM)
      potentiated the stimulation of I(K,ACh) elicited by low concentrations of ACh (1
      2 nM) in rat atrial myocytes. The threshold stimulation of I(K,ACh) elicited by
      internal 5'-guanylylimidodiphosphate (10 microM) was also potentiated by NO
      donors. SNAP (1 microM) did not modify I(K,ACh) reconstituted in human embryonic
      kidney 293 cells, in the absence or in the presence of ACh (1 or 10 nM). Taken
      together, these data suggest that NO is a cGMP-independent modulator of G-protein
      coupled muscarinic and beta-adrenergic receptor actions on cardiac ion channels.
      Although this action of NO seemed to occur at the level of G proteins, it
      appeared to require a component distinct from receptors, G proteins or their
      effectors.

PMID- 11956333
TI  - Rat nicotinic ACh receptor alpha7 and beta2 subunits co-assemble to form
      functional heteromeric nicotinic receptor channels.
AB  - Rat hippocampal interneurons express diverse subtypes of functional nicotinic
      acetylcholine receptors (nAChRs), including alpha7-containing receptors that have
      properties unlike those expected for homomeric alpha7 nAChRs. We previously
      reported a strong correlation between expression of the alpha7 and of the beta2
      subunits in individual neurons. To explore whether co-assembly of the alpha7 and
      beta2 subunits might occur, these subunits were co-expressed in Xenopus oocytes
      and the functional properties of heterologously expressed nAChRs were
      characterized by two-electrode voltage clamp. Co-expression of the beta2 subunit,
      both wild-type and mutant forms, with the alpha7 subunit significantly slowed the
      rate of nAChR desensitization and altered the pharmacological properties. Whereas
      ACh, carbachol and choline were full or near-full agonists for homomeric alpha7
      receptor channels, both carbachol and choline were only partial agonists in
      oocytes expressing both alpha7 and beta2 subunits. In addition the EC(50) values
      for all three agonists significantly increased when the beta2 subunit was co
      expressed with the alpha7 subunit. Co-expression with the beta2 subunit did not
      result in any significant change in the current-voltage curve. Biochemical
      evidence for the co-assembly of the alpha7 and beta2 subunits was obtained by co
      immunoprecipitation of these subunits from transiently transfected human
      embryonic kidney (TSA201) cells. These data provide direct biophysical and
      molecular evidence that the nAChR alpha7 and beta2 subunits co-assemble to form a
      functional heteromeric nAChR with functional and pharmacological properties
      different from those of homomeric alpha7 channels. This co-assembly may help to
      explain nAChR channel diversity in rat hippocampal interneurons, and perhaps in
      other areas of the nervous system.

PMID- 11956335
TI  - Synaptic transmission in the auditory brainstem of normal and congenitally deaf
      mice.
AB  - The deafness (dn/dn) mutant mouse provides a valuable model of human congenital
      deafness. We investigated the properties of synaptic transmission in the
      anteroventral cochlear nucleus (AVCN) of normal and congenitally deaf dn/dn mice.
      Excitatory postsynaptic currents (EPSCs) were evoked by focal stimulation of
      single auditory nerve fibres, and measured by whole-cell recordings from neurones
      in AVCN slices (mean postnatal age = P13). Absolute amplitudes of both AMPA- and
      NMDA-mediated components of evoked EPSCs were greater (170 %) in deaf versus
      control animals. Enhanced transmission in deaf mice was due to a presynaptic
      mechanism. Variance-mean analysis revealed that the probability of transmitter
      release was significantly greater in deaf (P(r) = 0.8) versus control animals
      (P(r) = 0.5). Following high frequency stimulation, deaf mice showed a greater
      depression of evoked EPSCs, and a significant increase in the frequency of
      delayed-release (asynchronous) miniature EPSCs (aEPSCs) (deaf 100 Hz vs. control
      7 Hz). The acetoxymethyl ester of EGTA (EGTA-AM) blocked the increase in
      miniature aEPSCs and returned tetanic depression to control values. In deaf mice,
      reduction of mean P(r) using cadmium caused an expected increase in paired-pulse
      ratio (PPR). However, in the same cells, a similar reduction in release by EGTA
      AM did not result in a change in PPR, demonstrating that a change may occur in
      P(r) without a concomitant change in PPR. In many respects, transmission in deaf
      mice was found to be remarkably similar to control mice, implying that many
      parameters of synaptic transmission develop normally in these animals. The two
      significant differences (higher P(r) and asynchronous release in deaf mice) could
      both be reversed by the addition of EGTA-AM, suggesting that endogenous calcium
      buffering may be impaired or undeveloped in the presynaptic terminals of the
      auditory nerve in deaf mice.

PMID- 11956334
TI  - Differential ontogeny of GABA(B)-receptor-mediated pre- and postsynaptic
      modulation of GABA and glycine transmission in respiratory rhythm-generating
      network in mouse.
AB  - Rhythm generation in mature respiratory networks is influenced strongly by
      synaptic inhibition. In early neonates, GABA(A)-receptor- and glycine-receptor
      mediated inhibition is not present, thus the question arises as to whether
      GABA(B)-receptor-mediated inhibition plays an important role. Using brainstem
      slices of neonatal mice (postnatal day, P0-P15), we analysed the role of GABA(B)
      mediated modulation of GABA and glycine synaptic transmission in the respiratory
      network. Blockade of GABA uptake by nipecotic acid (0.25-2 mM) reduced the
      respiratory frequency. This reduction was prevented by the selective GABA(B)
      receptor antagonist CGP55845A (CGP) alone at P0-P3, but by bicuculline as well as
      CGP at P7-P15. Blockade of GABA(B) receptors by CGP increased the respiratory
      frequency at P0-P3, whereas it caused a reduction of frequency in older animals.
      The effect of CGP on respiratory frequency was diminished in the presence of
      bicuculline and strychnine in older but not in younger animals. The relative
      contribution of GABA(B)-receptor-mediated pre- and postsynaptic modulation was
      examined by analysing the effect of GABA(B) receptors on spontaneous and
      miniature IPSCs. In younger animals (P0-P3), the GABA(B) receptor agonist
      baclofen had no detectable effect on IPSC frequency, but caused a significant
      decrease in the amplitude. In older animals (P7-P15), baclofen decreased both the
      frequency and amplitude of spontaneous and miniature IPSCs. These results
      demonstrate that GABA(B)-receptor-mediated postsynaptic modulation plays an
      important role in the respiratory network from P0 on. GABA(B)-receptor-mediated
      presynaptic modulation develops with a longer postnatal latency, and becomes
      predominant within the first postnatal week.

PMID- 11956336
TI  - Role of cyclic GMP-dependent protein kinase in the contractile response to
      exogenous nitric oxide in rat cardiac myocytes.
AB  - Nitric oxide (NO) can directly modulate cardiac contractility by accelerating
      relaxation and reducing diastolic tone. The intracellular mechanisms underlying
      these contractile effects are poorly understood. Here we investigate the role of
      cyclic GMP-dependent protein kinase (PKG) in the contractile response to
      exogenous NO in rat ventricular myocytes. Isolated ventricular myocytes were
      stimulated electrically and contractility was assessed by measuring cell
      shortening. Some cells were loaded with the fluorescent Ca(2+) probe indo-1 AM
      for simultaneous assessment of the intracellular Ca(2+) transient. The NO donor
      diethylamine NONOate (DEA/NO, 10 microM) significantly increased resting cell
      length, reduced twitch amplitude and accelerated time to 50 % relaxation (to
      100.8 +/- 0.2, 83.7 +/- 3.0 and 88.9 +/- 3.7 % of control values, respectively).
      The contractile effects of DEA/NO occurred without significant changes in the
      amplitude or kinetics of the intracellular Ca(2+) transient, suggesting that the
      myofilament response to Ca(2+) was reduced. These effects were abolished by
      inhibition of either guanylyl cyclase (with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin
      1-one; ODQ, 10 microM) or PKG (with Rp-8-Br-cGMPs, 10 microM) suggesting that, at
      the concentration investigated, the effects of DEA/NO were mediated exclusively
      by PKG, following activation of guanylyl cyclase and elevation of cGMP. Direct
      activation of PKG with 8-pCPT-cGMP (10 microM) mimicked the effects of DEA/NO
      (resting cell length and time to 50 % relaxation were 100.6 +/- 0.1 and 90.5 +/-
      1.5 % of control values, respectively).The reduced myofilament Ca(2+)
      responsiveness was not attributable to an intracellular acidosis since the small
      reduction in pH(i) induced by DEA/NO was found to be uncoupled from its
      contractile effects. However, hearts treated with DEA/NO (10 microM) showed a
      significant increase (1.4-fold; P < 0.01) in troponin I phosphorylation compared
      to control, untreated hearts. These results suggest that the reduction in
      myofilament Ca(2+) responsiveness produced by DEA/NO results from phosphorylation
      of troponin I by PKG.

PMID- 11956337
TI  - Cytosolic Ca(2+) and Ca(2+)-activated Cl(-) current dynamics: insights from two
      functionally distinct mouse exocrine cells.
AB  - The dynamics of Ca(2+) release and Ca(2+)-activated Cl(-) currents in two
      related, but functionally distinct exocrine cells, were studied to gain insight
      into how the molecular specialization of Ca(2+) signalling machinery are utilized
      to produce different physiological endpoints: in this case, fluid or exocytotic
      secretion. Digital imaging and patch-clamp methods were used to monitor the
      temporal and spatial properties of changes in cytosolic Ca(2+) concentration
      ([Ca(2+)](c)) and Cl(-) currents following the controlled photolytic release of
      caged-InsP(3) or caged-Ca(2+). In parotid and pancreatic acinar cells, changes in
      [Ca(2+)](c) and activation of a Ca(2+)-activated Cl(-) current occurred with
      close temporal coincidence. In parotid, a rapid global Ca(2+) signal was
      invariably induced, even with low-level photolytic release of threshold amounts
      of InsP(3). In pancreas, threshold stimulation generated an apically delimited
      [Ca(2+)](c) signal, while a stronger stimulus induced a global [Ca(2+)](c) signal
      which exhibited characteristics of a propagating wave. InsP(3) was more effective
      in parotid, where [Ca(2+)](c) signals initiated with shorter latency and
      exhibited a faster time-to-peak than in pancreas. The increased potency of
      InsP(3) in parotid probably results from a four-fold higher number of InsP(3)
      receptors as measured by radiolabelled InsP(3) binding and western blot analysis.
      The Ca(2+) sensitivity of the Cl(-) channels in parotid and pancreas was
      determined from the [Ca(2+)]-current relationship measured during a dynamic
      'Ca(2+) ramp' produced by the continuous, low-level photolysis of caged-Ca(2+).
      In addition to a greater number of InsP(3) receptors, the Cl(-) current density
      of parotid acinar cells was more than four-fold greater than that of pancreatic
      cells. Whereas activation of the current was tightly coupled to increases in
      Ca(2+) in both cell types, local Ca(2+) clearance was found to contribute
      substantially to the deactivation of the current in parotid. These data reveal
      specializations of common modules of Ca(2+)-release machinery and subsequent
      effector activation that are specifically suited to the distinct functional roles
      of these two related cell types.

PMID- 11956339
TI  - Compatible osmolytes modulate the response of porcine endothelial cells to
      hypertonicity and protect them from apoptosis.
AB  - Porcine pulmonary arterial endothelial cells accumulated myo-inositol and
      taurine, as well as betaine, during adaptation to hypertonic stress. The cells
      grew and maintained their normal morphology during culture in hypertonic (0.5
      osmol (kg H(2)O)(-1)) medium that contained osmolytes such as betaine, myo
      inositol or taurine at concentrations close to reported physiological values. The
      cells did not grow well in hypertonic medium depleted of potential compatible
      osmolytes. After a few days, cell density decreased by about 50 % and many cells
      rounded up and detached from the plates, their nuclei showing clear apoptotic
      morphology. The caspase-3 activity of the cells also increased dramatically under
      these conditions, but remained negligibly low when betaine and myo-inositol were
      added to the medium. Addition of betaine and myo-inositol to hypertonic medium
      depleted of compatible osmolytes increased the number of colonies remaining after
      12 days of culture; with each solute at 30-100 micromol l(-1) the number
      increased about sixfold. In the absence of compatible osmolytes, increased mRNA
      levels and corresponding activities of betaine/gamma-aminobutyric acid
      transporter (BGT1) and sodium/myo-inositol transporter (SMIT) induced by
      hypertonicity remained high after 72 h incubation, whereas they were down
      regulated in the presence of betaine and myo-inositol. Similarly, the down
      regulation of the amino acid System A transporter (ATA2) was markedly slowed in
      the absence of compatible osmolytes. We conclude that these compatible osmolytes
      at concentrations close to physiological values enable the endothelial cells to
      adapt to hypertonic stress, protecting them from apoptosis, and also modulate the
      adaptation process.

PMID- 11956338
TI  - Thin filament near-neighbour regulatory unit interactions affect rabbit skeletal
      muscle steady-state force-Ca(2+) relations.
AB  - The role of cooperative interactions between individual structural regulatory
      units (SUs) of thin filaments (7 actin monomers : 1 tropomyosin : 1 troponin
      complex) on steady-state Ca(2+)-activated force was studied. Native troponin C
      (TnC) was extracted from single, de-membranated rabbit psoas fibres and replaced
      by mixtures of purified rabbit skeletal TnC (sTnC) and recombinant rabbit sTnC
      (D27A, D63A), which contains mutations that disrupt Ca(2+) coordination at N
      terminal sites I and II (xxsTnC). Control experiments in fibres indicated that,
      in the absence of Ca(2+), both sTnC and xxsTnC bind with similar apparent
      affinity to sTnC-extracted thin filaments. Endogenous sTnC-extracted fibres
      reconstituted with 100 % xxsTnC did not develop Ca(2+)-activated force. In fibres
      reconstituted with mixtures of sTnC and xxsTnC, maximal Ca(2+)-activated force
      increased in a greater than linear manner with the fraction of sTnC. This
      suggests that Ca(2+) binding to functional Tn can spread activation beyond the
      seven actins of an SU into neighbouring units, and the data suggest that this
      functional unit (FU) size is up to 10-12 actins. As the number of FUs was
      decreased, Ca(2+) sensitivity of force (pCa(50)) decreased proportionally. The
      slope of the force-pCa relation (the Hill coefficient, n(H)) also decreased when
      the reconstitution mixture contained < 50 % sTnC. With 15 % sTnC in the
      reconstitution mixture, n(H) was reduced to 1.7 +/- 0.2, compared with 3.8 +/-
      0.1 in fibres reconstituted with 100 % sTnC, indicating that most of the
      cooperative thin filament activation was eliminated. The results suggest that
      cooperative activation of skeletal muscle fibres occurs primarily through spread
      of activation to near-neighbour FUs along the thin filament (via head-to-tail
      tropomyosin interactions).

PMID- 11956341
TI  - Development of membrane conductance improves coincidence detection in the nucleus
      laminaris of the chicken.
AB  - Coincidence detection at the nucleus laminaris (NL) of a chicken was improved
      between embryos (embryonic days (E) 16 and 17) and chicks (post-hatch days (P) 2
      7) in slice preparations. Electrical stimuli were applied bilaterally to the
      projection fibres to the NL at various intervals. The response window
      corresponding to the temporal separation of electrical stimuli that resulted in
      half-maximal firing probability was adopted as the measure of coincidence
      detection, and was narrower in chicks (1.4 ms) than in embryos (3.9 ms). Between
      these two ages, the membrane time constant of NL neurons was reduced from 18.4 to
      3.2 ms and the membrane conductance was increased 5-fold, while no difference was
      measured in the input capacitance. Evoked EPSCs decayed slightly faster in
      chicks, while the size and the time course of miniature EPSCs were unchanged.
      Action potentials had lower thresholds and larger after-hyperpolarization in
      chicks than in embryos. Dendrotoxin-I depolarized cells and increased their input
      resistance significantly at both ages, eliminated the after-hyperpolarization,
      and delayed the decay phase of action potentials, indicative of the expression of
      low-threshold K(+) channels. Cs(+) hyperpolarized the cells, increased the input
      resistance and eliminated sags during hyperpolarization at both ages, while the
      hyperpolarization sag was affected by neither Ba(2+) nor TEA. These data indicate
      the expression of hyperpolarization-activated cation channels. Between these two
      ages, the maximum conductance of low-threshold K(+) channels increased 4-fold to
      about 16 nS, and hyperpolarization-activated channels increased 6-fold to about
      10 nS. Improvement of coincidence detection correlated with the acceleration of
      the EPSP time course as a result of the increase of these conductances.

PMID- 11956340
TI  - A fundamental oscillatory state of isolated rodent hippocampus.
AB  - Population neuronal rhythms of various frequencies are observed in the rodent
      hippocampus during distinct behavioural states. However, the question of whether
      the hippocampus exhibits properties of spontaneous rhythms and population
      synchrony in isolation has not been definitively answered. To address this, we
      developed a novel preparation for studying neuronal rhythms in a relatively large
      hippocampal tissue in vitro. We isolated the whole hippocampus from mice up to 28
      days postnatal age, removing the dentate gyrus while preserving the functional
      CA3-to-CA1 connections. Placing the hippocampal isolate in a perfusion chamber
      for electrophysiological assessment extracellular recordings from the CA1
      revealed rhythmic field potential of 0.5 to </= 4 Hz that occurred spontaneously
      and propagated along the ventro-dorsal hippocampal axis. We provide convergent
      evidence, via measurements of extracellular pH and K(+), recordings of synaptic
      and intracellular activities and morphological assessments, verifying that these
      rhythms were not the consequence of hypoxia. Data obtained via simultaneous
      extracellular and patch clamp recordings suggest that the spontaneous rhythms
      represent a summation of GABAergic IPSPs originating from pyramidal neurons,
      which result from synchronous discharges of GABAergic inhibitory interneurons.
      Similar spontaneous field rhythms were also observed in the hippocampal isolate
      prepared from young gerbils and rats. Based on these data, we postulate that the
      spontaneous rhythms represent a fundamental oscillatory state of the hippocampal
      circuitry isolated from extra-hippocampal inputs.

PMID- 11956342
TI  - Calcium and calcium-activated currents in vagotomized rat primary vagal afferent
      neurons.
AB  - Adult inferior vagal ganglion neurons (nodose ganglion neurons, NGNs) were
      acutely isolated 4-6 days after section of their peripheral axons (vagotomy) and
      examined with the whole-cell patch-clamp technique. A subset (approximately 25 %)
      of vagotomized NGNs displayed depolarizing after-potentials (DAPs), not present
      in control NGNs. DAPs were inhibited by niflumic acid (125 microM) or cadmium
      (100 microM), and had a reversal potential near E(Cl), indicating that they were
      due to Ca(2+)-activated chloride current (I(Cl(Ca))). N-type, L-type, T-/R- and
      other types of voltage-dependent Ca(2+) channels provided about 43, 2, 16 and 40
      % of the trigger Ca(2+) for DAP generation, respectively. Intracellular Ca(2+)
      concentration ([Ca(2+)](i)) was estimated using fura-2 fluorescence. Resting
      [Ca(2+)](i) and peak [Ca(2+)](i) elevation induced by activating Ca(2+)-induced
      Ca(2+) release (CICR) stores with 10 mM caffeine were not significantly different
      among control NGNs, vagotomized NGNs with DAPs and vagotomized NGNs without DAPs,
      averaging 54 +/- 7.9 (n = 19; P = 0.49) and 2022 +/- 1059 nM (n = 19; P = 0.44),
      respectively. Blocking CICR with 10 microM ryanodine reduced DAP amplitude by
      approximately 37 %. Ca(2+) influx induced by action potential waveforms was
      increased by over 250 % in vagotomized NGNs with DAPs (19.0 +/- 2.1 pC) compared
      to control NGNs (5.0 +/- 0.8 pC) or vagotomized NGNs without DAPs (7.0 +/- 0.8
      pC). L-type, N-type, T-/R-type and other types of Ca(2+) influx were increased
      proportionately in vagotomized NGNs with DAPs. In conclusion, a subset of
      vagotomized NGNs have increased Ca(2+) currents and express I(Cl(Ca)). These NGNs
      respond electrically to increases in [Ca(2+)](i) during regeneration.

PMID- 11956344
TI  - Contractile properties of in situ perfused skeletal muscles from rats with
      congestive heart failure.
AB  - We hypothesized that in congestive heart failure (CHF) slow-twitch but not fast
      twitch muscles exhibit decreased fatigue resistance in the sense of accelerated
      reduction of muscle force during activity. Experiments were carried out on
      anaesthetized rats 6 weeks after induction of myocardial infarction or a sham
      operation (Sham). Animals with left ventricular end-diastolic pressure (LVEDP) >
      15 mmHg under anaesthesia were selected for the CHF group. There was no muscle
      atrophy in CHF. Force generation by in situ perfused soleus (Sol) or extensor
      digitorum longus (EDL) muscles was recorded during stimulation (trains at 5 Hz
      for 6 s (Sol) or 10 Hz for 1.5 s (EDL) at 10 or 2.5 s intervals, respectively)
      for 1 h in Sol and 10 min in EDL at 37 degrees C. Initial force was almost the
      same in Sol from CHF and Sham rats, but relaxation was slower in CHF. Relaxation
      times (95-5 % of peak force) were 177 +/- 55 and 131 +/- 44 ms in CHF and Sham,
      respectively, following the first stimulation train. After 2 min of stimulation
      the muscles transiently became slower and maximum relaxation times were 264 +/-
      71 and 220 +/- 45 ms in CHF and Sham, respectively (P < 0.05). After 60 min they
      recovered to 204 +/- 60 and 122 +/- 55 ms in CHF and Sham, respectively (P <
      0.05). In CHF but not in Sham rats the force of contraction of Sol declined from
      the second to the sixtieth minute to 70 % of peak force. The EDL of both CHF and
      Sham fatigued to 24-28 % of initial force, but no differences in contractility
      pattern were detected. Thus, slow-twitch muscle is severely affected in CHF by
      slower than normal relaxation and significantly reduced fatigue resistance, which
      may explain the sensation of both muscle stiffness and fatigue in CHF patients.

PMID- 11956343
TI  - Evidence that ventilatory rhythmogenesis in the frog involves two distinct
      neuronal oscillators.
AB  - In Rana catesbeiana the upper airways are used for two distinct yet highly
      coordinated ventilatory behaviours: buccal ventilation and lung inflation cycles.
      How these behaviours are generated and coordinated is unknown. The purpose of
      this study was to identify putative rhythmogenic brainstem loci involved in these
      ventilatory behaviours. We surveyed the isolated postmetamorphic brainstem to
      determine sites where local depolarization, produced by microinjecting the non
      NMDA glutamate receptor agonist, AMPA, augmented the ventilatory motor patterns.
      Two sites were identified: a caudal site, at the level of cranial nerve (CN) X,
      where AMPA injections caused increased buccal burst frequency but abolished lung
      bursts, and a rostral site, between the levels of CN VIII and IX, where
      injections increased the frequency of both types of ventilatory bursts. These two
      sites were further examined using GABA microinjections to locally inhibit cells.
      GABA injected into the caudal site suppressed the buccal rhythm but the lung
      rhythm continued, albeit at a different frequency. When GABA was injected into
      the rostral site the lung bursts were abolished but the buccal rhythm continued.
      When the two sites were physically separated by transection, both rostral and
      caudal brainstem sections were capable of rhythmogenesis. The results suggest the
      respiratory network within the amphibian brainstem is composed of at least two
      distinct but interacting oscillators, the buccal and lung oscillators. These
      putative oscillators may provide a promising experimental model for studying
      coupled oscillators in vertebrates.

PMID- 11956345
TI  - Development of T-tubular vacuoles in eccentrically damaged mouse muscle fibres.
AB  - Single fibres were dissected from mouse flexor digitorum brevis muscles and
      subjected to a protocol of eccentric stretches consisting of ten tetani each with
      a 40 % stretch. Ten minutes later the fibres showed a reduced force, a shift in
      the peak of the force-length relation and a steepening of the force-frequency
      relation. Addition of the fluorescent dye sulforhodamine B to the extracellular
      space enabled the T-tubular system to be visualized. In unstimulated fibres and
      fibres subjected to 10 isometric tetani, the T-tubules were clearly delineated.
      Sulforhodamine B diffused out of the T-tubules with a half-time of 18 +/- 1 s.
      Following the eccentric protocol, vacuoles connected to the T-tubules were
      detected in six out of seven fibres. Sulforhodamine B diffused out of the
      vacuoles of eccentrically damaged fibres extremely slowly with a half-time of 6.3
      +/- 2.4 min and diffused out of the T-tubules with a half-time of 39 +/- 4 s.
      Vacuole production was eliminated by application of 1 mM ouabain to the muscle
      during the eccentric protocol. On removal of the ouabain, vacuoles appeared over
      a period of 1 h and were more numerous and more widely distributed than in the
      absence of ouabain. We propose that T-tubules are liable to rupture during
      eccentric contraction probably because of the relative movement associated with
      the inhomogeneity of sarcomere lengths. Such rupture raises intracellular sodium
      and when the sodium is pumped from the cell by the sodium pump, the volume load
      of Na(+) and water exceeds the capacity of the T-tubules and causes vacuole
      production. The damage to the T-tubules may underlie a number of the functional
      changes that occur in eccentrically damaged muscle fibres.

PMID- 11956346
TI  - Oxytocin mediates stress-induced analgesia in adult mice.
AB  - As a neurohormone and as a neurotransmitter, oxytocin has been implicated in the
      stress response. Descending oxytocin-containing fibres project to the dorsal horn
      of the spinal cord, an area important for processing nociceptive inputs. Here we
      tested the hypothesis that oxytocin plays a role in stress-induced analgesia and
      modulates spinal sensory transmission. Mice lacking oxytocin exhibited
      significantly reduced stress-induced antinociception following both cold-swim (10
      degrees C, 3 min) and restraint stress (30 min). In contrast, the mice exhibited
      normal behavioural responses to thermal and mechanical noxious stimuli and
      morphine-induced antinociception. In wild-type mice, intrathecal injection of the
      oxytocin antagonist dOVT (200 microM in 5 microl) significantly attenuated
      antinociception induced by cold-swim. Immunocytochemical staining revealed that,
      in the mouse, oxytocin-containing neurones in the paraventricular nucleus of the
      hypothalamus are activated by stress. Furthermore, oxytocin-containing fibres
      were present in the dorsal horn of the spinal cord. To test whether descending
      oxytocin-containing fibres could alter nociceptive transmission, we performed
      intracellular recordings of dorsal horn neurones in spinal slices from adult
      mice. Bath application of oxytocin (1 and 10 microM) inhibited excitatory
      postsynaptic potentials (EPSPs) evoked by dorsal root stimulation. This effect
      was reversed by the oxytocin antagonist dOVT (1 microM). Whole-cell recordings of
      dorsal horn neurones in postnatal rat slices revealed that the effect of oxytocin
      could be blocked by the addition of GTP-gamma-S to the recording pipette,
      suggesting activation of postsynaptic oxytocin receptors. We conclude that
      oxytocin is important for both cold-swim and restraint stress-induced
      antinociception, acting by inhibiting glutamatergic spinal sensory transmission.

PMID- 11956347
TI  - The dependence of binocular contrast sensitivities on binocular single vision in
      normal and amblyopic human subjects.
AB  - We have measured monocular and binocular contrast sensitivities in response to
      medium to high spatial frequencies of vertical sinusoidal grating patterns in
      normal subjects, anisometropic amblyopes, strabismic amblyopes and non-amblyopic
      esotropes. On binocular viewing, contrast sensitivities were slightly but
      significantly increased in normal subjects, markedly increased in anisometropes
      and esotropes with anomalous binocular single vision (BSV) and significantly
      reduced in esotropes and exotropes without BSV. Application of a prismatic
      correction to the strabismic eye in order to achieve bifoveal stimulation
      resulted in a significant reduction in contrast sensitivity in esotropes with and
      without anomalous BSV, in exotropes and in non-amblyopic esotropes. Control
      experiments in normal subjects with monocular viewing showed that degradative
      effects of the prism occurred only with high prism powers and at high spatial
      frequencies, thus establishing that the reduced contrast sensitivities were the
      consequence of bifoveal stimulation rather than optical degradation. Displacement
      of the image of the grating pattern by 2 deg. in normal subjects and
      anisometropes by a dichoptic method to simulate a small angle esotropia had no
      effect on the contrast sensitivities recorded through the companion eye. By
      contrast, esotropes showed similar reductions in contrast sensitivity to those
      obtained with the prism experiments, confirming a fundamental difference between
      subjects with normal and abnormal ocular alignments. The results have thus
      established a suppressive action of the fovea of the amblyopic eye acting on the
      companion, non-amblyopic eye and indicate that correction of ocular misalignments
      in adult esotropes may be disadvantageous to binocular visual performance.

PMID- 11956348
TI  - Modulation of human corticomotor excitability by somatosensory input.
AB  - In humans, somatosensory stimulation results in increased corticomotoneuronal
      excitability to the stimulated body parts. The purpose of this study was to
      investigate the underlying mechanisms. We recorded motor evoked potentials (MEPs)
      to transcranial magnetic stimulation (TMS) from abductor pollicis brevis (APB),
      first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles. MEP
      amplitudes, recruitment curves (RC), intracortical inhibition (ICI),
      intracortical facilitation (ICF), resting (rMT) and active motor thresholds (aMT)
      were recorded before and after a 2-h period of ulnar nerve electrical stimulation
      at the wrist. Somatosensory input was monitored by recording somatosensory evoked
      potentials. To differentiate excitability changes at cortical vs. subcortical
      sites, we recorded supramaximal peripheral M-responses and MEPs to brainstem
      electrical stimulation (BES). In order to investigate the involvement of
      GABAergic mechanisms, we studied the influence of lorazepam (LZ) (a GABA(A)
      receptor agonist) relative to that of dextromethorphan (DM) (an NMDA receptor
      antagonist) and placebo in a double-blind design. We found that somatosensory
      stimulation increased MEP amplitudes to TMS only in the ADM, confirming a
      previous report. This effect was blocked by LZ but not by either DM or placebo
      and lasted between 8 and 20 min in the absence of (i) changes in MEPs elicited by
      BES, (ii) amplitudes of early somatosensory-evoked potentials or (iii) M
      responses. We conclude that somatosensory stimulation elicited a focal increase
      in corticomotoneuronal excitability that outlasts the stimulation period and
      probably occurs at cortical sites. The antagonistic effect of LZ supports the
      hypothesis of GABAergic involvement as an operating mechanism.

PMID- 11956349
TI  - In vivo muscle fibre behaviour during counter-movement exercise in humans reveals
      a significant role for tendon elasticity.
AB  - Six men performed a single ankle plantar flexion exercise in the supine position
      with the maximal effort with counter movement (CM, plantar flexion preceded by
      dorsiflexion) and without counter movement (NoCM, plantar flexion only) produced
      by a sliding table that controlled applied load to the ankle (40 % of the maximal
      voluntary force). The reaction force at the foot and ankle joint angle were
      measured using a force plate and a goniometer, respectively. From real-time
      ultrasonography of the gastrocnemius medialis muscle during the movement, the
      fascicle length was determined. The estimated peak force, average power, and work
      at the Achilles' tendon during the plantar flexion phase in CM were significantly
      greater than those in NoCM. In CM, in the dorsiflexion phase, fascicle length
      initially increased with little electromyographic activity, then remained
      constant while the whole muscle-tendon unit lengthened, before decreasing in the
      final plantar flexion phase. In NoCM, fascicle length decreased throughout the
      movement and the fascicle length at the onset of movement was longer than that of
      the corresponding phase in CM. It was concluded that during CM muscle fibres
      optimally work almost isometrically, by leaving the task of storing and releasing
      elastic energy for enhancing exercise performance to the tendon.

PMID- 11956350
TI  - Thermosensitivity of muscle: high-intensity thermal stimulation of muscle tissue
      induces muscle pain in humans.
AB  - Small-calibre afferent units responding to thermal stimuli have previously been
      reported to exist in muscle. The question as to whether these receptors in humans
      mediate subjective thermal sensations from muscle remains unresolved. The aims of
      the present study were to determine in humans whether intramuscular injection of
      warm and cold isotonic saline elicits temperature sensations, muscle pain or any
      other sensations. In 15 subjects, no thermal sensations assessed on a temperature
      visual analogue scale (VAS) could be detected with intramuscular injections of
      isotonic saline (1.5 ml) into the anterior tibial muscle at temperatures ranging
      from 8 to 48 degrees C. The same subjects recorded strongly increasing scores on
      a temperature VAS when thermal stimuli in the same intensity range were applied
      to the skin overlying the muscle by a contact thermode. However, I.M. isotonic
      saline of 48 degrees C induced muscle pain with peak scores of 3.2 +/- 0.8 cm on
      a VAS scale ranging from 0 to 10 cm. Using the the McGill pain questionnaire a
      subgroup, of subjects qualitatively described the pain using the 'thermal hot'
      and 'dullness' word groups. Temperature measurements within the muscle during the
      stimulating injections showed that the time course of the pain sensation elicited
      by saline at 48 degrees C paralleled that of the intramuscular temperature and
      far outlasted the injection time. The present data show that high-intensity
      thermal stimulation of muscle is associated with muscle pain. High-threshold warm
      sensitive receptors may mediate the pain following activation by temperatures of
      48 degrees C or more. Taken together, the data indicate that thermosensation from
      a given volume of muscle is less potent than nociception.

PMID- 11956351
TI  - Role of the medullary raphe in thermoregulatory vasomotor control in rats.
AB  - To investigate the involvement of the medullary raphe in thermoregulatory
      vasomotor control, we chemically manipulated raphe neuronal activity while
      monitoring the tail vasomotor response to preoptic warming. For comparison,
      neuronal activity in the rostral ventrolateral medulla (RVLM) was manipulated in
      similar experiments. Injections of D,L-homocysteic acid (DLH; 0.5 mM, 0.3 microl)
      into a restricted region of the ventral medullary raphe suppressed the tail
      vasodilatation normally elicited by warming the preoptic area to 42 degrees C.
      DLH injection into the RVLM also suppressed the vasodilatation elicited by
      preoptic warming. Injection of bicuculline (0.5 mM, 0.3 microl) into the same
      raphe region suppressed the vasodilatation elicited by preoptic warming.
      Bicuculline injection into the RVLM did not suppress tail vasodilatation. These
      results suggest that neurones in both the medullary raphe and the RVLM are
      vasoconstrictor to the tail, but only those in the raphe receive inhibitory input
      from the preoptic area. That input might be direct and/or indirect (e.g. via the
      periaqueductal grey matter).

PMID- 11956352
TI  - Vago-sympathoadrenal reflex in thermogenesis induced by osmotic stimulation of
      the intestines in the rat.
AB  - Duodenal infusion of hypertonic solutions elicits osmolality-dependent
      thermogenesis in urethane-anaesthetized rats. Here we investigated the
      involvement of the autonomic nervous system, adrenal medulla and brain in the
      mechanism of this thermogenesis. Bilateral subdiaphragmatic vagotomy greatly
      attenuated the first hour, but not the later phase, of the thermogenesis induced
      by 3.6 % NaCl (10 ml kg(-1)). Neither atropine pretreatment (10 mg kg(-1), I.P.)
      nor capsaicin desensitization had any effect on the osmotically induced
      thermogenesis, suggesting the involvement of non-nociceptive vagal afferents.
      Bilateral splanchnic denervation caudal to the suprarenal ganglia also had no
      effect, suggesting a lack of involvement of spinal afferents and sympathetic
      efferents to the major upper abdominal organs. Adrenal demedullation greatly
      attenuated the initial phase, but not the later phase, of thermogenesis.
      Pretreatment with the beta-blocker propranolol (20 mg kg(-1), I.P.) attenuated
      the thermogenesis throughout the 3 h observation period. The plasma adrenaline
      concentration increased significantly 20 min after osmotic stimulation but
      returned to the basal level after 60 min. The plasma noradrenaline concentration
      increased 20 min after osmotic stimulation and remained significantly elevated
      for 120 min. Therefore, adrenaline largely mediated the initial phase of
      thermogenesis, and noradrenaline was involved in the entire thermogenic response.
      Moreover, neither decerebration nor pretreatment with the antipyretic
      indomethacin (10 mg kg(-1), S.C.) had any effect. Accordingly, this thermogenesis
      did not require the forebrain and was different from that associated with fever.
      These results show the critical involvement of the vagal afferents, hindbrain and
      sympathoadrenal system in the thermogenesis induced by osmotic stimulation of the
      intestines.

PMID- 11956353
TI  - Postprandial hypotension in response to duodenal glucose delivery in healthy
      older subjects.
AB  - Postprandial hypotension occurs frequently in older people and may lead to
      syncope and falls. Some recent studies suggest that the magnitude of the
      postprandial fall in blood pressure (BP) is influenced by the rate of gastric
      emptying. The aim of this study was, therefore, to determine whether the fall in
      blood pressure induced by intraduodenal glucose is influenced by the rate of
      nutrient delivery into the small intestine, bypassing the effects of gastric
      emptying. Eight healthy elderly subjects (four male and four female, age 70.3 +/-
      3.4 years) were studied on two separate days, in double-blind, randomised order.
      Glucose was infused intraduodenally at a rate of either 1 or 3 kcal min(-1), for
      60 min, (0-60 min) followed by 0.9 % saline for a further 60 min (60-120 min).
      Blood pressure and heart rate were recorded at baseline and every 3 min during
      the study. Blood glucose and plasma insulin were also determined. Only the 3 kcal
      min(-1) infusion caused a significant fall in systolic (P < 0.001) and diastolic
      (P < 0.0001) blood pressure and an increase in the heart rate (P < 0.0001). The
      rises in blood glucose (P < 0.01) and plasma insulin (P < 0.05) concentrations
      were greater during the 3 kcal min(-1) infusion. We conclude that in healthy
      older subjects, the magnitude of the fall in blood pressure and increase in heart
      rate induced by intraduodenal glucose infusion is dependent on the rate of
      nutrient delivery into the small intestine. These results may have relevance to
      the treatment of postprandial hypotension.

PMID- 11956354
TI  - The intent to exercise influences the cerebral O(2)/carbohydrate uptake ratio in
      humans.
AB  - During and after maximal exercise there is a 15-30 % decrease in the metabolic
      uptake ratio (O(2)/[glucose + 1/2 lactate]) and a net lactate uptake by the human
      brain. This study evaluated if this cerebral metabolic uptake ratio is influenced
      by the intent to exercise, and whether a change could be explained by substrates
      other than glucose and lactate. The arterial-internal jugular venous differences
      (a-v difference) for O(2), glucose and lactate as well as for glutamate,
      glutamine, alanine, glycerol and free fatty acids were evaluated in 10 healthy
      human subjects in response to cycling. However, the a-v difference for the amino
      acids and glycerol did not change significantly, and there was only a minimal
      increase in the a-v difference for free fatty acids after maximal exercise. After
      maximal exercise the metabolic uptake ratio of the brain decreased from 6.1 +/-
      0.5 (mean +/- S.E.M.) at rest to 3.7 +/- 0.2 in the first minutes of the recovery
      (P < 0.01). Submaximal exercise did not change the uptake ratio significantly.
      Yet, in a second experiment, when submaximal exercise required a maximal effort
      due to partial neuromuscular blockade, the ratio decreased and remained low (4.9
      +/- 0.2) in the early recovery (n = 10; P < 0.05). The results indicate that
      glucose and lactate uptake by the brain are increased out of proportion to O(2)
      when the brain is activated by exhaustive exercise, and that such metabolic
      changes are influenced by the will to exercise. We speculate that the uptake
      ratio for the brain may serve as a metabolic indicator of 'central fatigue'.

PMID- 11956355
TI  - Depression of hypoxic arousal response in adolescent mice following antenatal
      vasoactive intestinal polypeptide blockade.
AB  - Late-gestation blockade of vasoactive intestinal polypeptide (VIP) activity in
      pregnant mice produces discrete morphological abnormalities in the somatosensory
      cortex of offspring. We investigated the functional implications of this lesion
      on the behavioural arousal response to moderate hypoxia. Pregnant mice received
      twice-daily injections of 200 microl saline (control), or saline + 50 microg VIP
      antagonist (anti-VIP) on embryonic days 17 and 18. Offspring were studied
      unrestrained at 6-7 weeks after birth, in a bias-flow whole-body plethysmograph
      during behavioural quiet sleep. Arousal was defined by movement (MVT) lasting >
      or =1 s. Hypoxic ventilatory (HVR) and arousal responses were measured during a 5
      min exposure to 10 % O(2)-3 % CO(2) (hypoxia); peripheral chemoreflex drive was
      estimated by transient hyperoxia administered at rest and end-hypoxia (Dejours
      type test). MVTs increased in all mice during hypoxia, but in anti-VIP mice: (a)
      MVT onset was delayed (174 +/- 90 vs. 108 +/- 59 s from the start of hypoxia,
      anti-VIP vs. control; P = 0.008); and (b) MVTs were less frequent, and total MVT
      time in hypoxia was less (8 +/- 7 vs. 15 +/- 9 %; P = 0.03). The HVR, and
      peripheral drive at rest and end-hypoxia were comparable in control and anti-VIP
      mice. In conclusion, a significant arousal deficit was evident in anti-VIP mice.
      This was not associated with obviously deranged peripheral or brainstem-mediated
      responses to hypoxia during sleep. This may signal a general deficit in the way
      hypoxic distress is monitored and processed, and arousal initiated and sustained
      in these mice.

PMID- 11956356
TI  - Is autonomic support of arterial blood pressure related to habitual exercise
      status in healthy men?
AB  - We determined if the tonic autonomic nervous system (ANS) contribution to
      arterial blood pressure (BP) maintenance in humans is related to habitual
      endurance exercise status. Twenty-three healthy young (age 18-31 years) males, 11
      endurance exercise-trained and 12 untrained, were studied. Maximal oxygen
      consumption was higher (P < 0.001) and resting heart rate and body fatness were
      lower (P < 0.05) in the exercise-trained men. Plasma noradrenaline concentrations
      and BP decreased from baseline levels in response to ganglionic blockade
      (intravenous trimethaphan) in both groups (all P < 0.001). The absolute (Delta
      mmHg: systolic = -35 +/- 2 vs. -32 +/- 4; diastolic = -13 +/- 2 vs. -10 +/- 2;
      mean = -21 +/- 2 vs. -17 +/- 3) and relative (Delta%: systolic = -35 +/- 2 vs. 
      31 +/- 3; diastolic = -26 +/- 3 vs. -20 +/- 3; mean = -31 +/- 2 vs. -26 +/- 3)
      decreases in BP were not significantly different between the endurance-trained
      and untrained men. There were no significant group differences in the heart rate,
      stroke volume, cardiac output or systemic vascular resistance (conductance)
      responses to trimethaphan. Systemic vascular alpha-adrenergic sensitivity (slope
      of the increase in mean BP with incremental phenylephrine infusion during
      ganglionic blockade) also did not differ in the two groups (endurance-trained:
      3.2 +/- 0.5; untrained: 3.2 +/- 0.7 mmHg (ng phenylephrine)(-1) (ml plasma)(-1)).
      In the pooled sample, the decrease in mean BP during trimethaphan was related to
      baseline and changes in plasma noradrenaline concentrations (r = 0.58-0.65, P <
      0.001) and alpha-adrenergic sensitivity (r = 0.49, P < 0.02). Our results suggest
      that the endurance exercise-trained state is not obviously associated with
      altered ANS support of BP in healthy young men. Basal sympathetic nervous system
      (SNS) activity and alpha-adrenergic vascular sensitivity are significant
      physiological correlates of ANS support of BP in this population.

PMID- 11956357
TI  - Haemodynamic changes during neck pressure and suction in seated and supine
      positions.
AB  - We sought to quantify the contribution of cardiac output (Q) and total vascular
      conductance (TVC) to carotid baroreflex-mediated changes in mean arterial
      pressure (MAP) in the upright seated and supine positions. Acute changes in
      carotid sinus transmural pressure were evoked using brief 5 s pulses of neck
      pressure and neck suction (NP/NS) via a simplified paired neck chamber that was
      developed to enable beat-to-beat measurements of stroke volume using pulse
      doppler ultrasound. Percentage contributions of Q and TVC were achieved by
      calculating the predicted change in MAP during carotid baroreflex stimulation if
      only the individual changes in Q or TVC occurred and all other parameters
      remained at control values. All NP and NS stimuli from +40 to -80 Torr (+5.33 to 
      10.67 kPa) induced significant changes in Q and TVC in both the upright seated
      and supine positions (P < 0.001). Cardiopulmonary baroreceptor loading with the
      supine position appeared to cause a greater reliance on carotid baroreflex
      mediated changes in Q. Nevertheless, in both the seated and supine positions the
      changes in MAP were primarily mediated by alterations in TVC (percentage
      contribution of TVC at the time-of-peak MAP, seated 95 +/- 13, supine 76 +/- 17
      %). These data indicate that alterations in vasomotor activity are the primary
      means by which the carotid baroreflex regulates blood pressure during acute
      changes in carotid sinus transmural pressure.

PMID- 11956360
TI  - Imaging of the chest after lung transplantation.
AB  - Lung transplantation is a well-accepted treatment for numerous lung diseases when
      medical or surgical therapy is ineffective or unavailable and the patient has a
      limited life expectancy (usually less than 2 to 3 years). When appropriate,
      single-lung transplantation is the preferred procedure because of a critical
      shortage of available donor lungs. Preoperative imaging is useful for selecting
      which lung should be transplanted, size matching between donor lung and recipient
      thorax, and screening for malignancy. Cardiac-related deaths, infection, and
      primary graft failure are the leading causes of perioperative death. Obliterative
      bronchiolitis is the "Achilles heel" of lung transplantation and accounts for the
      largest number of late deaths. This article reviews the preoperative,
      perioperative, and postoperative considerations and the utility of radiologic
      imaging after lung transplantation.

PMID- 11956358
TI  - Renal, cardiovascular and endocrine responses of fetal sheep at 0.8 of gestation
      to an infusion of amino acids.
AB  - Amino acid infusions increase renal blood flow (RBF) and glomerular filtration
      rate (GFR) and stimulate tubular reabsorption in adults. To characterize the
      effects of amino acids on fetal renal haemodynamics, tubular sodium reabsorption,
      acid-base homeostasis and plasma renin levels, 11 chronically catheterized fetal
      sheep aged 121 +/- 1 days (term ~150 days) were infused I.V. for 4 h with
      alanine, glycine, proline and serine (0.1, 0.1, 0.06 and 0.06 mmol min(-1),
      respectively) in 0.15 M saline at 0.165 ml min(-1). Eight control fetuses were
      given saline. During amino acid infusion, plasma amino acid levels increased up
      to 20-fold (P < 0.005). GFR increased by 50 +/- 8 % (P < 0.001); there was only a
      small transient increase in RBF. Proximal fractional sodium reabsorption fell
      from 74.6 +/- 2.9 to 55.5 +/- 5.4 % (P < 0.005). Distal sodium delivery
      increased, but a smaller percentage of this distal sodium load was reabsorbed (P
      < 0.005). Thus fractional sodium reabsorption fell from 95.5 +/- 0.9 to 81.4 +/-
      2.0 % (P < 0.005). There was a large diuresis, natriuresis, kaliuresis and
      increase in osmolar excretion (P < 0.005). Plasma sodium and chloride
      concentrations fell (P < 0.005). Plasma osmolality did not change. Plasma renin
      levels fell (P < 0.05), cortisol levels increased (P < 0.05), and there was a
      compensated metabolic acidosis. Thus the fetal sheep kidney demonstrated a
      remarkable functional capacity to respond to amino acid infusion. The increase in
      filtration fraction and the lack of an increase in RBF suggest that efferent
      arteriolar vasoconstriction occurred, a very different response from the renal
      vasodilatation seen in adult animals.

PMID- 11956361
TI  - Thoracic imaging in heart transplantation.
AB  - Heart transplantation remains the best treatment option for patients with end
      stage heart failure refractory to standard management. Thoracic imaging plays an
      important role in the preoperative and postoperative evaluation of cardiac
      transplant recipients. This article reviews the major complications of cardiac
      transplantation, including acute allograft rejection. Advances in the treatment
      of organ rejection have improved the long-term survival of cardiac transplant
      recipients. Rejection is now detected earlier with the help of endomyocardial
      biopsy and treated aggressively with improved immunosuppressive therapies. The
      estimated 1-year and 5-year survival rates of heart transplant recipients are 79%
      and 65%, respectively (2).

PMID- 11956362
TI  - Thoracic radiology in kidney and liver transplantation.
AB  - Renal transplantation accounts for more than half of all solid organ transplants
      performed in the U.S., and the liver is the second most commonly transplanted
      solid organ. Although abdominal imaging procedures are commonplace in these
      patients, there has been relatively little attention paid to thoracic imaging
      applications. Preoperative imaging is crucial to aid in the exclusion of
      infectious or malignant disease. In the perioperative time period, thoracic
      imaging focuses both on standard intensive care unit care, including monitoring
      devices and their complications, and on the early infections that can occur.
      Postoperative management is divided into three time periods, and the principles
      governing the occurrence of infections and malignancies are reviewed. Anatomic
      and pathologic aspects unique to kidney and liver transplantation patients are
      also discussed.

PMID- 11956363
TI  - Pulmonary complications in bone marrow transplantation.
AB  - This article reviews the most common pulmonary complications after bone marrow
      transplantation (BMT) and their radiologic presentations. An approach emphasizing
      the common complications that occur in relation to the immunosuppression recovery
      timeline is presented. An update on newer techniques of marrow transplantation
      and preparatory regimen drugs will be discussed. These newer techniques may have
      an effect on the radiologic appearance of some BMT complications. The diagnostic
      approach, management, and some evolving therapies of BMT patients with pulmonary
      complications will also be discussed.

PMID- 11956365
TI  - Leptospirosis of the lung: high-resolution computed tomography findings in five
      patients.
AB  - The authors report the high-resolution computed tomography findings in five
      patients with diffuse pulmonary hemorrhage caused by serologically proven
      leptospirosis. The main findings consisted of extensive ground-glass opacities
      and patchy areas of airspace consolidation.

PMID- 11956364
TI  - Influence of staging thoracic computed tomography on radiation therapy planning
      for esophageal carcinoma.
AB  - Radiation therapy with concurrent chemotherapy is frequently used as definitive
      treatment for esophageal carcinoma. Although thoracic computed tomography (CT) is
      widely used in staging esophageal carcinoma, its application to radiation therapy
      planning has been regarded as optional rather than mandatory. Conventional
      radiation therapy planning is esophagogram-based rather than CT-based. The
      treatment port is generated by adding 5 cm to the proximal and distal margins of
      the tumor-involved segment as seen on esophagogram performed in the treatment
      position. Historically, a maximum port length of 15 cm was recommended to avoid
      excessive treatment morbidity. The authors examined the limitations of such a
      planning protocol by projecting conventional treatment ports onto the thoracic CT
      of 75 consecutive newly diagnosed cases of nondisseminated esophageal squamous
      cell carcinoma. The authors assessed the adequacy of coverage of the primary
      tumor and metastatic nodes, with respect to data from thoracic CT and neck
      ultrasonography. It was found that up to 38% of T2-T3 tumors and 30% of short
      length (< or =5 cm) tumors had metastatic nodes outside the port. The addition of
      neck ultrasonography led to identification of an additional 5% of patients with
      nonpalpable nodes outside the port. It is concluded that the frequency of
      inadequate tumor coverage using an esophagogram-based planning protocol, with a
      maximum port length of 15 cm, is unacceptably high. Thoracic CT should be a
      mandatory rather than optional imaging investigation in guiding radiation therapy
      planning for esophageal cancer.

PMID- 11956366
TI  - Computed tomography diagnosis of macroscopic pulmonary fat embolism.
AB  - Pulmonary fat embolism probably occurs commonly after major orthopedic injuries
      and after orthopedic surgery. Furthermore, tiny fat emboli can often be shown by
      transesophageal echocardiography during orthopedic surgery. However, large
      macroscopic are rarely identified radiologically. Macroscopic fat emboli have
      been previously described in the common femoral vein and inferior vena cava on
      abdominal imaging. To the authors' knowledge, a macroscopic fat embolus in the
      pulmonary arteries has not been previously described. The authors report a case
      of a woman who, on computed tomography, had a large fat embolus after
      intramedullary rod placement for an isolated left femur fracture.

PMID- 11956367
TI  - Diffuse pulmonary involvement by mycosis fungoides: high-resolution computed
      tomography and pathologic findings.
AB  - The authors report the high-resolution computed tomography (HRCT) appearance of
      diffuse pulmonary involvement by mycosis fungoides in a 74-year-old woman whose
      clinical and radiographic manifestations simulated pneumonia. The HRCT showed
      multiple, dense, peribronchovascular nodules with surrounding ground-glass
      opacity and several wedge-shape peripheral opacities. The autopsy specimen
      revealed angiocentric and peribronchovascular involvement of mycosis fungoides
      and pulmonary infarctions distal to angiocentric infiltration of the tumor cells.

PMID- 11956368
TI  - Increased (18)fluorodeoxyglucose accumulation in mucosa-associated lymphoid
      tissue-type lymphoma of the lung.
AB  - The authors report a case of mucosa-associated lymphoid tissue (MALT)-type
      lymphoma of the lung that showed an increased accumulation of
      18fluorodeoxyglucose (FDG) on positron emission tomography. It should be
      considered that MALT-type lymphoma could be cause a increased FDG uptake in the
      lung.

PMID- 11956369
TI  - Alveolar adenoma of the lung: computed tomography and magnetic resonance imaging
      findings.
AB  - Alveolar adenoma of the lung is a rare benign neoplasm with distinctive gross and
      microscopic findings. Radiographically, alveolar adenoma usually presents as a
      well-circumscribed, peripheral, solitary nodule. The authors describe the
      contrast-enhanced computed tomography and magnetic resonance imaging features of
      alveolar adenoma of lung. Magnetic resonance imaging demonstrated the presence of
      a cystic space with central fluid and thin-rim enhancement. These findings are
      suggestive of a benign nodule, and alveolar adenoma of lung should be added to
      the differential diagnosis of nodules that demonstrate this pattern of
      enhancement and are probably benign.

PMID- 11956370
TI  - Nontraumatic pulmonary fat embolism syndrome: radiologic and pathologic
      correlations.
AB  - The authors report a case of pulmonary fat embolism syndrome without identifiable
      cause that was seen on chest radiographs and high-resolution computed tomography
      as diffuse ground-glass attenuation, particularly in nondependent portions of
      both lungs. The radiologic findings were shown on open-lung biopsy to represent
      diffuse pulmonary hemorrhage caused by fat embolism.

PMID- 11956372
TI  - Serum levels of Hsp 72 measured early after trauma correlate with survival.
AB  - BACKGROUND: Experimental studies have shown that hemorrhagic shock is associated
      with the expression of inducible heat proteins, especially heat shock protein
      (Hsp) 72, in liver, brain, heart, and kidney. Moreover, induction of Hsp 72 by
      various stressors before the onset of shock has been associated with the
      attenuation of organ injury caused by hemorrhage. However, it is not known
      whether Hsp 72 is expressed after severe trauma in humans. The purpose of this
      study was therefore to determine whether Hsp 72 could be detected in the serum of
      patients early after severe trauma and whether serum levels of Hsp 72 might
      correlate with survival of trauma patients or the severity of the postinjury
      inflammatory response. METHODS: Clinical data were collected prospectively over a
      3-year period for trauma patients mechanically ventilated for more than 2 days
      who met the following inclusion criteria: Injury Severity Score > or = 16, and
      age > 18 years. Physiologic data for quantitative assessment of organ dysfunction
      were collected for each patient. Hsp 72 and nitrate and nitrite levels were
      measured in the serum of trauma patients collected at or 12 to 48 hours after the
      admission to the emergency department. RESULTS: Sixty-seven patients with severe
      trauma were enrolled in the study. Hsp 72 was detected in the serum of all trauma
      patients. All patients with high initial serum levels of Hsp 72 (serum levels >
      15 ng/mL) survived, whereas 29% of the patients with low Hsp 72 serum levels died
      from their traumatic injuries (p = 0.01). The overall mortality was 21%,
      occurring within 5 to 7 days. Patients who died were older (mean age, 54 +/- 15
      years) than those who survived (mean age, 36 +/- 15 years) (p < 0.0.05). The
      cause of death was attributable to head injury in 79%, although the severity of
      head injury (Abbreviated Injury Scale score) was not statistically different
      between survivors with high serum values of Hsp 72 and patients who died. There
      was no correlation between the initial serum Hsp 72 values and the severity of
      organ dysfunction or clinical indicators of the inflammatory response.
      CONCLUSION: Hsp 72 can be detected in the serum of severely traumatized patients
      within 30 minutes after injury. Elevated initial serum levels of Hsp 72 (serum
      levels > 15 ng/mL) are associated with survival after severe trauma, but are not
      related to the incidence or severity of the postinjury inflammatory response or
      organ dysfunction.

PMID- 11956373
TI  - A prospective study for the detection of vascular injury in adult and pediatric
      patients with cervicothoracic seat belt signs.
AB  - BACKGROUND: A delayed diagnosis of injury to cervicothoracic vessels from blunt
      trauma may cause significant adverse sequelae. The association of a
      cervicothoracic seat belt sign with such an injury is unknown. METHODS:
      Algorithms were prospectively studied for the detection of occult vascular injury
      in patients with cervicothoracic seat belt signs. Patients with neck seat belt
      signs underwent arteriography or computed tomographic angiography (CTA). Those
      with thoracic seat belt signs underwent aortography/arteriography if a ruptured
      thoracic aorta or injury to a great vessel was suspected or a neurovascular
      abnormality was present. RESULTS: During a 17-month period, 797 patients were
      admitted to the trauma service secondary to motor vehicle crashes. One hundred
      thirty-one (16.4%) had cervical or thoracic seat belt signs. Four (3%) of the
      patients had carotid artery injuries, the presence of which was strongly
      associated with a Glasgow Coma Scale score < 14, an Injury Severity Score > 16 (p
      < 0.0001), and the presence of a clavicle and/or first rib fracture (p < 0.0037).
      Of the remaining patients, 17 had thoracic trauma. There were no vascular
      injuries in the children and only one had thoracic trauma. CONCLUSION: The
      algorithms are safe and accurate for the detection of cervicothoracic vascular
      injury in adult and pediatric patients with seat belt signs. The cervicothoracic
      seat belt mark and an abnormal physical examination are an effective combination
      in screening for cervicothoracic vascular injury.

PMID- 11956374
TI  - Amplified cytokine response and lung injury by sequential hemorrhagic shock and
      abdominal compartment syndrome in a laboratory model of ischemia-reperfusion.
AB  - BACKGROUND: Increased intra-abdominal pressure has been shown to result in a
      myriad of physiologic aberrations that result in the abdominal compartment
      syndrome (ACS). The clinically relevant combination of hemorrhagic shock and
      resuscitation and subsequent ACS, however, has not been studied in detail. We
      hypothesized that sequential hemorrhagic shock (HS) and ACS would result in
      greater cytokine activation and polymorphonuclear neutrophil (PMN)-mediated lung
      injury than with either insult alone. METHODS: Twenty Yorkshire swine (20-30 kg)
      were studied. Group 1 (n = 5) was hemorrhaged to a mean arterial pressure of 25
      to 30 mm Hg for 60 minutes and resuscitated to baseline mean arterial pressure.
      Intra-abdominal pressure was then increased to 30 mm Hg above baseline and
      maintained for 60 minutes. Group 2 (n = 5) was subjected to HS alone and Group 3
      (n = 5) to ACS alone. Group 4 (n = 5) had sham experiment without HS or ACS.
      Central and portal venous interleukin-1beta, interleukin-8, and tumor necrosis
      factor-alpha levels were serially measured. Bronchoalveolar lavage (BAL) for
      protein and PMNs was performed at baseline and 24 hours after resuscitation. Lung
      myeloperoxidase was evaluated at 24 hours after resuscitation. RESULTS: Portal
      and central vein cytokine levels were equivalent but were significantly higher in
      Group 1 than in other groups. BAL PMNs were higher (p < 0.05) in Group 1 (4.1 +/-
      2.0 x 106) than in the other groups (0.6 +/- 0.5, 1.4 +/- 1.3, and 0.1 +/- 0.0 x
      106, respectively) and lung myeloperoxidase activity was higher (p < 0.05) in
      Group 1 (134.6 +/- 57.6 x 106/g) than in the other groups (40.3 +/- 14.7, 46.1 +/
      22.4, and 7.73 +/- 4.4 x 106/g, respectively). BAL protein was higher (p < 0.01)
      in Group 1 (0.92 +/- 0.32 mg/mL) compared with the other groups (0.22 +/- 0.08,
      0.29 +/- 0.11, and 0.08 +/- 0.06 mg/mL, respectively). CONCLUSION: In this
      clinically relevant model, sequential insults of ischemia-reperfusion (HS and
      resuscitation) and ACS were associated with significantly increased portal and
      central venous cytokine levels and more severe lung injury than HS or ACS alone.

PMID- 11956375
TI  - Impact of deferred treatment of blunt diaphragmatic rupture: a 15-year experience
      in six trauma centers in Quebec.
AB  - BACKGROUND: The purpose of this study was to show that blunt diaphragmatic
      rupture does not require immediate emergency operation in the absence of other
      indications. METHODS: We reviewed all patients with blunt diaphragmatic rupture
      admitted within 24 hours of injury to one of six university trauma centers
      providing trauma care for the province of Quebec from April 1, 1984, to March 31,
      1999. Multivariate analysis of demographic profiles, severity indices,
      indications for operation, and preoperative delays was performed. RESULTS: There
      were 160 patients (91 men and 69 women) with blunt diaphragmatic rupture. Mean
      age was 40.1 +/- 16.2 years. Mean Injury Severity Score was 26.9 +/- 11.5 and
      mortality was 14.4%. Patients undergoing emergency surgery for indications other
      than diaphragmatic rupture had a significantly higher Injury Severity Score than
      those undergoing surgery for repair of diaphragmatic rupture alone (34.7 +/- 10.7
      vs. 22.0 +/- 9.0, p < 0.001). In patients undergoing surgery for diaphragmatic
      rupture alone, delay before repair of the diaphragmatic hernia did not lead to an
      increased mortality compared with patients undergoing immediate surgery (3.4% vs.
      5.0%, p = NS). CONCLUSION: Blunt diaphragmatic rupture in the absence of other
      surgical injuries carries low mortality. Operative repair of diaphragmatic
      rupture can be deferred without appreciable increased mortality if no other
      indication mandates immediate surgery.

PMID- 11956376
TI  - Factors influencing the decision to amputate or reconstruct after high-energy
      lower extremity trauma.
AB  - BACKGROUND: Factors thought to influence the decision for limb salvage include
      injury severity, physiologic reserve of the patient, and characteristics of the
      patient and their support system. METHODS: Eligible patients were between the
      ages of 16 and 69 with Gustilo type IIIB and IIIC tibial fractures, dysvascular
      limbs resulting from trauma, type IIIB ankle fractures, or severe open midfoot or
      hindfoot injuries. Data collected at enrollment relevant to the decision-making
      process included injury characteristics and its treatment, and the nature and
      severity of other injuries. Logistic regression and stepwise modeling were used
      to determine the effect of each covariate on the variable salvage/ amputation.
      RESULTS: Of 527 patients included in the analysis, 408 left the hospital with a
      salvaged limb. Of the 119 amputations performed, 55 were immediate and 64 were
      delayed. The multivariate analysis confirmed the bivariate analysis: all injury
      characteristics remained significant predictors of limb status with the exception
      of bone loss; and soft tissue injury and absence of plantar sensation were the
      most important factors in accounting for model validity. CONCLUSION: Soft tissue
      injury severity has the greatest impact on decision making regarding limb salvage
      versus amputation.

PMID- 11956378
TI  - Anterior tibiofibular ligament avulsion fracture in weber type B lateral
      malleolar fracture.
AB  - BACKGROUND: The purpose of this study was to determine the incidence,
      relationship with the ankle diastasis, and effect of treatment of the anterior
      tibiofibular ligament avulsion fracture (Wagstaffe fracture) combined with the
      Weber type B lateral malleolar fracture. METHODS: This study reviewed 94 cases of
      ankle fractures treated with operative methods. RESULTS: There were 52 cases of
      Weber type B lateral malleolar fractures and 13 cases of Wagstaffe fractures
      combined with them (25%). Ankle diastases were diagnosed in 20 cases (38.5%) in
      all Weber type B fractures and 11 (84.6%) of the 13 Wagstaffe fractures.
      CONCLUSION: The Wagstaffe fracture can be a good diagnostic clue of ankle
      diastasis in Weber type B lateral malleolar fracture. The accurate reduction and
      fixation of the avulsed fragment is important for restoration of the stable
      distal tibiofibular joint and to prevent the chronic ankle joint pain caused by
      impingement of the avulsed fragment.

PMID- 11956377
TI  - Unreamed intramedullary nail versus external fixation in grade III open tibial
      fractures.
AB  - BACKGROUND: The optimum method for skeletal stabilization of severe open
      fractures of the tibial shaft remains controversial. METHODS: We compared the
      results of the AO unreamed tibial nail (URTN) with external fixation (Ex-Fix) in
      the treatment of patients with a grade III injury of the tibial diaphysis. Thirty
      patients were retrospectively reviewed, with a mean follow-up of 25 months
      (range, 12-56 months). Seventeen patients were treated with external fixation
      (grade IIIA, 12 patients; grade IIIB, 4 patients; and grade IIIC, 1 patient) and
      13 with a URTN (grade IIIA, 6 patients; grade IIIB, 6 patients; and grade IIIC, 1
      patient). Both groups were comparable with respect to age, gender, fracture
      severity, and Injury Severity Score. RESULTS: Mean time to full weight bearing
      was 37.4 weeks in the Ex-Fix group versus 22.2 weeks in the URTN group (p =
      0.0069, t test). Seven patients in the Ex-Fix group required further surgery for
      nonunion versus two in the URTN group. There were four significant pin track
      infections. Removal of URTN was required in one case of deep infection.
      CONCLUSION: This study supports the use of the URTN over external fixation in the
      treatment of severe open tibial fractures.

PMID- 11956380
TI  - Predictors of outcome in head injury: proposal of a new scaling system.
AB  - BACKGROUND: In a statistical outcome analysis covering 10 years, 554 patients
      with isolated head trauma were analyzed. The aim of this study was to combine
      clinical and computed tomographic characteristics in a prognostic scoring system
      determining outcome after head injury. METHODS: After collection of data,
      mortality and morbidity were determined for each clinical and radiologic
      parameter; a different grading from 1 to 8 points was then attached to each
      parameter. The total score for each patient was calculated by adding the
      individual points from the different parameters. RESULTS: Significant differences
      in outcome (p < 0.01, Mann-Whitney U test) were registered in steps from 0 to 10
      points (group I), 11 to 20 points (group II), and > 20 points (group III). Group
      I had a mortality of 8.3%, and patients in groups II and III died in 51.2% and
      80.8%, respectively. Patients in group I had a Glasgow Outcome Scale (GOS) score
      of 4 and 5 in 19.4% and 56.7%, respectively, whereas group II reached a GOS score
      of 4 or 5 in only 9.9% and 1.7%, respectively. Patients in group III never
      reached a GOS score of 4 or 5. CONCLUSION: The presented scaling system allows a
      predictive value in mortality and morbidity to be determined for each patient
      suffering from brain trauma.

PMID- 11956379
TI  - Accidents in patients with insulin-treated diabetes: increased risk of low-impact
      falls but not motor vehicle crashes--a prospective register-based study.
AB  - BACKGROUND: Patients with diabetes mellitus may be at increased risk of
      accidents, mainly because of hypoglycemia. A variety of approaches have been
      adopted in an attempt to quantify this risk, but there has not been, to date, a
      systematic study using a national trauma register. In this study, we report
      findings from the Scottish Trauma Audit Group database. METHODS: The database
      includes all patients admitted to hospital for 3 or more days, or who died in
      hospital as a result of their accident. The study includes 11,244 cases aged 15
      years or over entered into the database between July 1996 and June 1998. This
      included 151 patients with insulin-treated diabetes. Using detailed prescribing
      information from one representative region, we have calculated the rates of
      different types of accidents for patients treated with insulin and compared this
      with the control population. We have analyzed information on the mechanism and
      severity of injury, outcome, and length of hospital stay. RESULTS: Overall, the
      rate of accidents for insulin-treated patients was estimated at 291.2 per 100,000
      population per year compared with 148.4 for the control population (p < 0.001;
      relative risk, 1.97; 95% confidence interval, 1.68-2.32). Insulin-treated
      patients were, on average, older (p < 0.005), more likely to be women (p < 0.02),
      and had longer stay in hospital (p < 0.001). The major excess of injuries related
      to low falls (< 2 m), which accounted for 62.3% of the injuries in the insulin
      treated group compared with 47.1% in the remainder (p < 0.01). Low falls in the
      insulin-treated group (n = 94) were examined in detail: compared with the control
      population, there was no difference in age and sex, Injury Severity Score,
      Revised Trauma Score (a measure of the severity of physiologic disturbance), or
      calculated probability of survival (TRISS). Length of inpatient stay was higher
      in the insulin-treated low-fall patients (10 vs. 7 days, p < 0.01). Of the 151
      catalogued injuries, the vast majority were fractures at peripheral sites. Only
      23 insulin-treated individuals were admitted after a motor vehicle crash during
      the study period. This represents a slight but not significant increase above the
      rate for the background population. CONCLUSION: This study confirms that patients
      taking insulin are at increased risk of accidents. Among the different types of
      injury, only low-impact falls were significantly increased. This is most likely
      related to an increased tendency for insulin-treated patients to fall during a
      hypoglycemic episode. However, patients with diabetes may also be at higher risk
      of sustaining a fracture after a fall. The number of car crashes involving
      drivers with insulin-dependent diabetes is small, and the rate is not
      significantly greater than that of the background population. Further study of
      the causes and consequences of falls in diabetic patients is warranted.

PMID- 11956381
TI  - Impact of alcohol intoxication on hemodynamic, metabolic, and cytokine responses
      to hemorrhagic shock.
AB  - BACKGROUND: Alcohol intoxication is associated with a high incidence of traumatic
      injury, particularly in the young healthy population. The impact of alcohol
      intoxication on the immediate pathophysiologic response to injury has not been
      closely examined. We hypothesized that acute alcohol intoxication would aggravate
      the immediate outcome from hemorrhagic shock by impairing homeostatic
      counterregulation to blood loss. METHODS: Chronically catheterized male Sprague
      Dawley rats were randomized to receive an intragastric infusion of ethyl alcohol
      (1.75 g/kg followed by 250-300 mg/kg/h) or isocaloric dextrose (3-mL bolus +
      0.375 mL/h) for 15 hours. Before initiating fixed-pressure hemorrhage followed by
      fluid resuscitation, an additional intragastric bolus of ethyl alcohol (1.75
      g/kg) was administered. Hemodynamic, metabolic, cytokine, and acid-base
      parameters were assessed during the hemorrhage period and at completion of
      resuscitation. Lungs were obtained for cytokine determinations. RESULTS: Basal
      mean arterial pressure was significantly lower in alcohol-intoxicated (blood
      alcohol concentration, 135 +/- 12 mg/dL) animals than in controls during baseline
      (20%) and after the initial fluid resuscitation period (30%). Hemorrhage
      decreased arterial HCO3 and Pco2, and increased Po2 without significant
      alteration in arterial blood pH. Alcohol intoxication blunted the decrease in
      Pco2 and increase in Po2 and decreased blood pH during baseline and throughout
      the course of the hemorrhage period. Hemorrhage produced marked and progressive
      elevations in plasma glucose and lactate levels in controls, and this was
      inhibited by alcohol intoxication. Hemorrhage elevated plasma tumor necrosis
      factor-alpha (TNF-alpha) (686 +/- 252 pg/mL) and interleukin (IL)-10 (178 +/- 25
      pg/mL), and did not alter IL-6 and IL-1 levels. Alcohol blunted the hemorrhage
      induced rise in plasma TNF-alpha (142 +/- 48 pg/mL) and enhanced the hemorrhage
      induced increase in IL-10 (678 +/- 187 pg/mL). Hemorrhage produced a two- to
      threefold increase in lung content of TNF-alpha, IL-1alpha, and IL-6 without
      significantly altering lung IL-10. Alcohol exacerbated the hemorrhage-induced
      increase in lung TNF-alpha, and did not alter the IL-1alpha, IL-6, and IL-10 lung
      responses. CONCLUSION: These results indicate marked alterations in the
      hemodynamic and metabolic responses to hemorrhagic shock by alcohol intoxication.
      Furthermore, our findings suggest that alcohol modulates the early
      proinflammatory responses to hemorrhagic shock. Taken together, these alterations
      in metabolic and inflammatory responses to hemorrhage are likely to impair
      immediate outcome and predispose to tissue injury.

PMID- 11956383
TI  - Radiologic screening for midfacial fractures: a single 30-degree occipitomental
      view is enough.
AB  - BACKGROUND: The standard radiologic screening views for maxillofacial trauma in
      the accident and emergency department have been the Waters (30-degree
      occipitomental [OM]) view, the Caldwell (posteroanterior) view, and the lateral
      view. We wanted to see if a single 30-degree occipitomental view would be
      sufficient to screen for maxillofacial trauma (excluding nasal fractures).
      METHODS: Over a 1-year period, each of 730 patients had three radiologic views
      obtained for maxillofacial trauma at our emergency department. A consultant
      emergency physician read the single OM view for injury, and then compared his
      radiologic findings with those made by other doctors on the basis of the three
      views. The need for further computed tomographic scanning was also studied.
      RESULTS: There were 730 patients recruited, of which 104 patients had abnormal
      findings on three-view screening. All the radiologic abnormalities were seen on
      the OM view; however, for the same 104 patients, only 48 had abnormal findings on
      the Caldwell views. Radiologic detail for the latter 48 patients was less obvious
      on the Caldwell views compared with the OM views. Other than two mandible
      fractures, no facial abnormality was demonstrable on any of the lateral views,
      even with significant bony injury on the OM views. CONCLUSION: A single 30-degree
      occipitomental view would be sufficient to screen for maxillofacial trauma.
      Further views are unnecessary and add little clinical value. Computed tomographic
      scanning with three-dimensional reconstruction of the facial skeleton should be
      the next preferred investigation for any patient found to have fractures on the
      Waters views.

PMID- 11956382
TI  - Burn depth affects dermal interstitial fluid pressure, free radical production,
      and serum histamine levels in rats.
AB  - BACKGROUND: We measured the amount of edema and the free radical production in
      burn-injured skin and the serum histamine levels, as well as changes in dermal
      interstitial fluid pressure. METHODS: Thirty-six Wistar rats with 20% total body
      surface area burns of different depth were resuscitated by lactated Ringer's
      solution intravenously. The rats were divided into a deep burn (DB) group (n =
      12), a superficial dermal burn (SDB) group (n = 12), and a sham burn (Sham) group
      (n = 12). Dermal interstitial fluid hydrostatic pressure (Pif), total skin water
      and xanthine oxidase activity, and serum histamine levels were measured until 60
      minutes postburn. RESULTS: In the DB group, dermal Pif significantly fell to 
      35.9 +/- 11.0 and -40.9 +/- 7.0 mm Hg at 10 and 15 minutes postburn, respectively
      (p < 0.05); it returned to preburn values at 50 minutes postburn. In the SDB
      group, dermal Pif was slightly negative but did not markedly change. Total skin
      water was significantly higher than that of the DB and the Sham groups; however,
      in the SDB group, serum histamine and dermal xanthine oxidase were significantly
      higher than in the DB group at 15, 30, and 45 minutes postburn (p < 0.05).
      CONCLUSION: The fluid-resuscitated DB produced a more negative dermal Pif than
      the SDB, but less dermal edema. In contrast, the SDB appeared to mainly generate
      dermal edema formation by wound free radical production and serum histamine
      release. The dermal Pif is one of the factors associated with edema formation
      immediately after deep burns. However, an increase in vascular permeability
      associated with oxygen radical production plays a more important role in dermal
      edema formation than does dermal Pif.

PMID- 11956385
TI  - The role of restraint and seat position in pediatric facial fractures.
AB  - BACKGROUND: Recently, head and brain injuries were identified as consequences of
      the inappropriate use of seat belts by children. The proposed mechanism of these
      injuries might also place a child at risk for facial fracture. METHODS: A
      probability sample of children under age 16 involved in crashes were enrolled in
      an ongoing crash surveillance system (1998-2001) that links insurance claims data
      to telephone survey and crash investigation data (unweighted, n = 12,659;
      weighted, n = 131,717). Incidence of facial fracture was estimated and a series
      of cases were examined using in-depth crash investigation to identify the
      mechanisms of these injuries, specifically, the role of seating position and
      restraint use in the mechanism of injury. RESULTS: Ninety-two children suffered a
      fracture of the facial bones (0.07% of all children in crashes). Among restrained
      children with facial fractures (n = 68), those inappropriately restrained were at
      a 1.6-fold higher risk (95% confidence interval, 1.2-2.1; p = 0.001) of
      significant injury than those appropriately restrained for their age. The in
      depth investigations revealed that excessive head excursion resulting from
      suboptimal torso restraint caused facial impact, which resulted in the facial
      injuries described. CONCLUSION: The potential for disfigurement associated with
      these facial injuries may resonate strongly with parents, and prevention of
      disfigurement may provide additional motivation for proper restraint, in
      particular, booster seats and rear seat location, for this pediatric population.

PMID- 11956386
TI  - Periaortic hematoma on abdominal computed tomographic scanning as an indicator of
      thoracic aortic rupture in blunt trauma.
AB  - BACKGROUND: In our institution, we have noted an association between periaortic
      hematomas (PH) present on abdominal computed tomographic (CT) scans and patients
      with thoracic aortic rupture (TAR) in blunt trauma. This 5-year retrospective
      study determined the sensitivity and specificity of PH and left hemothorax seen
      on abdominal CT scan as an indicator of TAR. METHODS: The trauma registry and
      records identified 54 blunt trauma patients who had a CT scan of the abdomen and
      an arch aortogram. Fourteen patients with TAR and 40 patients without TAR were
      selected for analysis. A digital photograph of an upper cut of the abdominal CT
      scan for each patient was examined by radiology staff for the presence or absence
      of PH and left hemothorax. RESULTS: The sensitivity, specificity, positive
      predictive value, and negative predictive value of PH as a predictor of TAR were
      88%, 99%, 97%, and 96%, respectively. CONCLUSION: The finding of PH on CT scan of
      the abdomen in blunt trauma patients should alert the clinician to the high
      likelihood of thoracic aortic injury.

PMID- 11956387
TI  - Early use of recombinant factor VIIa improves mean arterial pressure and may
      potentially decrease mortality in experimental hemorrhagic shock: a pilot study.
AB  - BACKGROUND: Recombinant factor VIIa (rFVIIa) is used for treatment of bleeding
      episodes in hemophilia patients who develop inhibitors to factors VIII and IX. We
      tested the hypothesis that administration of rFVIIa early after injury would
      decrease bleeding and improve survival after experimental hepatic trauma.
      METHODS: Anesthetized swine were cannulated for blood sampling and hemodynamic
      monitoring. Avulsion of left median lobe of the liver induced uncontrolled
      hemorrhage. After a 10% reduction of mean arterial pressure, animals were blindly
      randomized to receive intravenous rFVIIa (180 microg/kg) (n = 6) or placebo (n =
      7). RESULTS: Mortality was 43% (three of seven) in controls versus 0% with rFVIIa
      (p = 0.08, chi2). Significantly shorter prothrombin time and higher mean arterial
      pressures were observed in the rFVIIa group. CONCLUSION: Intravenous
      administration of rFVIIa early after induction of hemorrhage shortens prothrombin
      time and improves mean arterial pressure. A trend toward improved survival was
      observed.

PMID- 11956388
TI  - Multiple head injuries in rats: effects on behavior.
AB  - BACKGROUND: Evidence suggests that mild head injuries in humans can result in
      cumulative damage. No investigation to date has considered the effects of
      multiple subacute mild head injuries in an animal model. METHODS: Forty-one male
      Long-Evans hooded rats were trained in a Morris water maze. All animals were
      fitted with a hollow intracranial screw. Concussions were generated using a fluid
      percussion device. Animals were then evaluated in the water maze until
      performance returned to baseline. Control animals received no concussions. The
      remaining animals were randomized to receive one, two, or three concussions.
      Animals were allowed to return to baseline after each concussion and were then
      killed. Motor performance was evaluated on a balance beam both before and after
      concussions. RESULTS: After one concussion, 85% of animals showed performance
      deviation from baseline as measured by time to reach the platform, returning to
      baseline within a mean of 14.0 trials. After two concussions, 48% of animals
      showed deviation, with a mean return to baseline of 6.8 trials. After three
      concussions, 25% of animals showed deviation, with a mean return to baseline of
      2.3 trials. Of postconcussive animals, 42% developed new inconsistent baseline
      levels of performance. Balance beam performance was unaffected. CONCLUSION:
      Multiple concussions cause immediate transient impairment in spatial recognition
      and have extended effects on baseline performance in rats. Motor performance is
      not affected.

PMID- 11956389
TI  - Missed injuries in a level I trauma center.
AB  - BACKGROUND: Major trauma presents major diagnostic and therapeutic problems. Any
      delay in providing the treatment necessary may lead to increased morbidity and
      mortality, prolonged length of hospital stay, and increased cost. This study was
      undertaken to determine the extent, contributing factors, and implication of
      missed injuries and relate them to the three surveys in a Danish Level I trauma
      center. METHODS: The records of all major traumatized patients admitted to the
      Odense University Hospital from January 1996 through December 1999 have been
      studied to determine the extent and type of missed injuries. The initial
      examination is carried out by the trauma team in the A&E department according to
      standard protocols. Resuscitation is carried out according to Advanced Trauma
      Life Support principles and details are documented in the patient journal and in
      a special trauma journal. RESULTS: Sixty-four of 786 patients (incidence, 8.1%)
      had 86 missed injuries. The missed injuries averaged 1.3 injuries per patient.
      There were 45 male and 19 female patients, with a median age of 33 years (range,
      12-81 years). The median ISS was 17 (range, 4-50); 14%, 38%, and 48% of the
      injuries were missed in primary, secondary, and tertiary surveys, respectively.
      CONCLUSION: Our study demonstrates that missed injuries can occur at any stage of
      the management of patients with major trauma. Repeated assessments, both clinical
      and radiologic, are mandatory to diminish the problem. In initial assessment, one
      still has to treat the greatest threat to life before complete diagnosis of all
      injuries, but alertness to evolving injuries must remain throughout the patient's
      stay in hospital.

PMID- 11956390
TI  - In vivo characterization of the molecular-genetic changes in gastric mucosa
      during the development of acute gastritis and stress ulceration.
AB  - BACKGROUND: Trauma patients are at risk for the development of stress ulceration.
      Stress ulceration should be associated with increased heat-shock gene (iHSP70)
      and an inhibition of the trefoil peptide, spasmolytic polypeptide (SP), and mucin
      (MUC5AC) gene expressions. METHODS: Male Sprague-Dawley rats (10 weeks old) were
      restrained for 0-, 4-, 8-, 12-, and 24-hour periods of time. Gastric ulcers were
      graded using a one- to three-point scoring system. The level of mucosal gene
      expression was determined at each time point for three genes: iHSP70, SP, and
      MUC5AC. RESULTS: Gastric ulceration developed in direct proportion to the
      duration of restraint. Gastric ulceration was preceded by increased iHSP70 and
      decreased SP and MUC5AC gene expressions. CONCLUSION: Restraint-induced gastric
      ulceration was preceded by an up-regulation of iHSP70 and a down-regulation of SP
      and MUC5AC gene expressions.

PMID- 11956391
TI  - Surgical stabilization of internal pneumatic stabilization? A prospective
      randomized study of management of severe flail chest patients.
AB  - BACKGROUND: We compared the clinical efficacy of surgical stabilization and
      internal pneumatic stabilization in severe flail chest patients who required
      prolonged ventilatory support. METHODS: Thirty-seven consecutive severe flail
      chest patients who required mechanical ventilation were enrolled in this study.
      All the patients received identical respiratory management, including end
      tracheal intubation, mechanical ventilation, continuous epidural anesthesia,
      analgesia, bronchoscopic aspiration, postural drainage, and pulmonary hygiene. At
      5 days after injury, surgical stabilization with Judet struts (S group, n = 18)
      or internal pneumatic stabilization (I group, n = 19) was randomly assigned. Most
      respiratory management was identical between the two groups except the surgical
      procedure. Statistical analysis using two-way analysis of variance and Tukey's
      test was used to compare the groups. RESULTS: Age, sex, Injury Severity Score,
      chest Abbreviated Injury Score, number of rib fractures, severity of lung
      contusion, and Pao2/Fio2 ratio at admission were all equivalent in the two
      groups. The S group showed a shorter ventilatory period (10.8 +/- 3.4 days) than
      the I group (18.3 +/- 7.4 days) (p < 0.05), shorter intensive care unit stay (S
      group, 16.5 +/- 7.4 days; I group, 26.8 +/- 13.2 days; p < 0.05), and lower
      incidence of pneumonia (S group, 24%; I group, 77%; p < 0.05). Percent forced
      vital capacity was higher in the S group at 1 month and thereafter (p < 0.05).
      The percentage of patients who had returned to full-time employment at 6 months
      was significantly higher in the S group (11 of 18) than in the I group (1 of 19).
      CONCLUSION: This study proved that in severe flail chest patients, surgical
      stabilization using Judet struts has beneficial effects with respect to less
      ventilatory support, lower incidence of pneumonia, shorter trauma intensive care
      unit stay, and reduced medical cost than internal fixation. Moreover, surgical
      stabilization with Judet struts improved percent forced vital capacity from the
      early phase after surgical fixation. Also, patients with surgical stabilization
      could return to their previous employment quicker than those with internal
      pneumatic stabilization, even in those with the same severity of flail chest. We
      therefore concluded that surgical stabilization with Judet struts may be
      preferably applied to patients with severe flail chest who need ventilator
      support.

PMID- 11956392
TI  - Locked nailing with interfragmentary wiring for humeral nonunions.
AB  - OBJECTIVE: Locked nailing for humeral nonunions is threatened by residual
      fracture gap and fracture motion. This article describes the clinical experience
      of using interfragmentary wiring to solve these problems. METHODS:
      Interfragmentary wiring was used in 21 consecutive humeral nonunions treated with
      humeral locked nails. The average age of patients was 49.5 years, with an average
      nonunion duration of 14.4 months. Eighteen patients had previous operations.
      Nonunions were located at the proximal third in 4, the middle third in 10, and
      the distal third in 7. Antegrade nailing was used in 11 and retrograde nailing in
      10. Sixteen nonunions were nailed with 8-mm nails and five with 7-mm nails.
      Interfragmentary wiring was applied to either the posterior or the lateral cortex
      of humeri in a figure-of-eight configuration. Bone grafting was performed in all
      and average follow-up time was 22 months. RESULTS: With a single operation, all
      patients achieved osseous union in, on average, 18.3 weeks. One patient with
      segmental nonunion suffered acute renal failure 4 months after operation, but
      fracture healing was not affected. Wire infection occurred in one patient with
      preoperative infection at the nail entry site and was treated by implant removal.
      Other complications including two transient radial nerve palsies and one brachial
      artery injury did not affect the final outcome. At follow-up, all but four
      patients had complete recovery of shoulder flexion and abduction. The average
      postoperative Neer score (91.1 points) was significantly better than the average
      preoperative score (65.5 points). All but three patients had complete recovery of
      elbow motion. CONCLUSION: Interfragmentary wiring, a safe procedure if properly
      performed, could effectively decrease the residual fracture gap and fracture
      motion in locked nailing of humeral nonunions. Further biomechanical studies and
      prospective, randomized, controlled studies are warranted.

PMID- 11956393
TI  - Popliteal traumatic arteriovenous fistulas.
AB  - BACKGROUND: The purpose of this report is to analyze the clinical presentation,
      diagnosis, and outcome of surgical treatment in patients with popliteal
      arteriovenous fistulas (AVFs) in order to make trauma surgeons aware of the
      various issues patients with popliteal AVFs might present. METHODS: From 1991 to
      2000, 49 patients were treated for traumatic AVF. Among these patients, seven
      suffered from popliteal AVF of various durations. The patients were men and
      ranged in age from 17 to 27 years, with a mean age of 22.4 years. The time from
      injury to admission to our institutions varied from 5 days to 2 years. A
      diagnosis of popliteal AVF was made after clinical examinations revealed thrill
      and bruit over the injury sites. The diagnosis was confirmed in four of the
      patients after they underwent angiography. Patients with long-standing popliteal
      AVF underwent cardiology examinations to check for signs of heart failure. All
      patients with popliteal AVF received surgical treatment. Five patients had major
      blood vessels reconstructed, one patient had a minor blood vessel ligated, and
      another patient had a minor blood vessel reconstructed. RESULTS: Five of the
      seven patients experienced no postoperative difficulties. No serious heart
      failure occurred; however, there were signs of cardiac overload in three of the
      five patients. The two remaining patients of the seven underwent leg amputations.
      However, one of the two patients had a gangrenous foot at admission to our
      institution, and vascular reconstruction on the other patient was unsuccessful.
      For all seven patients, the average hospital stay in the vascular surgery
      department was 16.2 days and the follow-up ranged from 2 to 44 months, with a
      mean of 21.5 months. CONCLUSION: Trauma of the popliteal space requires special
      attention, since blood vessel injuries in that zone might result in serious
      complications. Popliteal traumatic AVFs result in a high rate of leg amputation
      and long-standing fistulas produce cardiac overload. The presence of thrill and
      bruit over the injury site should alert the examiner to consider the existence of
      AVF. Angiography is a reliable diagnostic tool, and should be used in all vitally
      stable patients. Surgical or nonsurgical closure of AVF will prevent local and
      systemic complications that might be irreversible in long-standing fistulas.

PMID- 11956394
TI  - Restraint use and injury patterns among children involved in motor vehicle
      collisions.
AB  - BACKGROUND: Motor vehicle collisions are the leading cause of death among
      children older than 1 year. Use of appropriate restraint systems is associated
      with reductions in morbidity and mortality in this age group. No studies have
      evaluated the association between specific injury patterns and restraint use
      among children. The purpose of this study was to evaluate differences in risks of
      injuries in different body regions according to restraint use among children 0 to
      11 years of age. METHODS: The 1995 to 1999 National Automotive Sampling System
      data files were used. The National Automotive Sampling System is a national
      probability sample of passenger vehicles involved in police-reported tow-away
      collisions. Information on occupant (seating position, restraint use), collision
      (change in velocity, vehicle intrusion), and outcome characteristics was
      evaluated. Risks of injuries in different body regions (Abbreviated Injury Scale,
      1990 Revision score > or = 2) were calculated and compared according to restraint
      use. RESULTS: Between 1995 and 1999, there were approximately 1.5 million
      children 0 to 11 years of age involved in police-reported tow-away MVCs who met
      the inclusion criteria for this study. Compared with unrestrained children,
      properly restrained children had significantly lower overall injury risk (risk
      ratio [RR], 0.37); significant risk reductions were also observed for injuries to
      the head (RR, 0.18), thorax (RR, 0.35), and lower extremities (RR, 0.26), and
      mortality (RR, 0.26). Significant risk reductions were not noted when comparing
      improperly restrained children with unrestrained children. CONCLUSION: Proper
      restraint use among children is associated with lower risk of injury. Educational
      initiatives should focus not only on encouraging restraint use but also on
      ensuring that parents know the appropriate age-dependent restraint method and how
      to use it properly.

PMID- 11956395
TI  - An analysis of race and demographic factors among motor vehicle fatalities.
AB  - BACKGROUND: According to the National Highway Traffic Safety Administration, from
      1982 through 1995 safety belts are estimated to have saved 74,769 lives. Even
      more lives could be saved and serious injuries avoided if there was increased
      seat belt use in the United States. METHODS: This study analyzed safety belt use
      among drivers and passengers involved in fatal motor vehicle crashes from 1993
      through 1995. Age, sex, race, safety belt use, and position in the vehicle were
      the demographic factors obtained from both the Fatality Analysis Reporting System
      and the National Highway Traffic Safety Administration. RESULTS: Overall, safety
      belt use increased by an average of 1.3% per year for the entire study
      population. Forward logistic regression identified age, female gender, Caucasian
      race, and driver as significant predictors of safety belt use. CONCLUSION: This
      study has identified younger males, African Americans, and passengers as high
      risk populations for nonuse of safety belts among fatal motor vehicle crashes.
      These high-risk populations should be educated regarding the importance of safety
      belt use.

PMID- 11956396
TI  - Myodesis: a novel approach to the repair of complex traumatic hernias.

PMID- 11956397
TI  - Severe blunt cardiac injury in an infant: a case of child abuse.

PMID- 11956399
TI  - Penetration of the chest by less-than-lethal "beanbag" shotgun rounds.

PMID- 11956398
TI  - Right atrial and ventricular thrombi after blunt chest trauma.

PMID- 11956400
TI  - Enhanced recognition of "lung sliding" with power color Doppler imaging in the
      diagnosis of pneumothorax.

PMID- 11956401
TI  - Bullet embolization from the left internal iliac vein to the right ventricle.

PMID- 11956402
TI  - Endovascular management of carotid and basilar artery occlusion secondary to
      trauma of the thoracic aorta: case report.

PMID- 11956403
TI  - Vascular reconstruction of hepatic artery injury using the gastroduodenal artery:
      6-year follow-up-case report.

PMID- 11956404
TI  - Intrasplenic posttraumatic pseudoaneurysm secondary to spleen-salvaging surgery.

PMID- 11956405
TI  - Intrapancreatic bile duct injury: case report.

PMID- 11956406
TI  - Kasabach-Merritt syndrome complicating the treatment of a femoral shaft fracture
      in an adult.

PMID- 11956407
TI  - Colorectal blowout from compressed air: case report.

PMID- 11956408
TI  - Methemoglobinemia as a cause of respiratory failure.

PMID- 11956409
TI  - Biochemical serum markers of traumatic brain injury.

PMID- 11956410
TI  - A new approach to extraperitoneal rectal injuries: laparoscopy and diverting loop
      colostomy.

PMID- 11956411
TI  - When is the safest time to undertake secondary definitive fracture stabilization
      procedures in multiply injured patients who were initially managed using a
      strategy of primary temporary skeletal fixation.

PMID- 11956412
TI  - Can D-dimer levels exclude thromboembolism in severely injured patients?

PMID- 11956413
TI  - Unintentional death, suicide, and domestic homicide against the improbable threat
      of an undefined terrorist or criminal threat.

PMID- 11956415
TI  - Osteoporosis in men treated with androgen deprivation therapy for prostate
      cancer.
AB  - PURPOSE: We surveyed the growing literature on osteoporosis secondary to androgen
      deprivation therapy and provide suggestions regarding its identification and
      treatment. MATERIALS AND METHODS: We reviewed pertinent studies of male
      osteoporosis, osteoporotic fracture incidence or bone mineral density loss as a
      possible side effect of prostate cancer treatment and potential therapies for
      this side effect. RESULTS: Hypogonadism is a well-known cause of secondary
      osteoporosis in men. There is evidence of decreased bone mineral density with all
      types of androgen deprivation therapy, presumably due to its anti-testosterone
      effect. Bone mineral density loss is 3% to 5% yearly in the first few years of
      androgen deprivation therapy with an increase in osteoporotic fracture incidence.
      There are little data on potential treatments, although bisphosphonates and
      intermittent androgen deprivation therapy may have salutary effects. CONCLUSIONS:
      Osteoporosis is an important and debilitating side effect of androgen deprivation
      therapy, although precise estimates of its incidence, degree and cost are not
      completely elucidated. Until more data are available, it is prudent for all men
      beginning androgen deprivation therapy to receive calcium and vitamin D, and
      maintain a moderate exercise regimen. Baseline and at least 1 followup bone
      density measurement seem appropriate with bisphosphonate treatment a possibility
      in those in whom osteoporosis develops. More research is needed to explore the
      effect of bisphosphonates, calcium and vitamin D supplementation, exercise,
      calcitonin, selective estrogen re-uptake inhibitors, estrogens and intermittent
      androgen deprivation therapy on the course of androgen deprivation therapy
      induced osteoporosis. The osteoporotic fracture incidence and bone mineral
      density should be regularly incorporated into studies involving the hormonal
      treatment of prostate cancer.

PMID- 11956416
TI  - First clinical experience with extracorporeally induced destruction of kidney
      stones by shock waves. 1981.

PMID- 11956417
TI  - Radio frequency ablation of renal cell carcinoma: preliminary clinical
      experience.
AB  - PURPOSE: We assess the feasibility, safety and efficacy of radio frequency
      ablation of small peripheral renal cell carcinomas. MATERIALS AND METHODS: Five
      patients with a histologically proven renal cell carcinoma 30 to 40 mm. in
      diameter were treated with radio frequency ablation. A triple needle electrode
      was percutaneously advanced into each tumor under sonographic (4 cases) or
      computerized tomography (CT) (1) guidance. The radio frequency generator was
      activated for 15 minutes in each location where the electrode had been placed.
      Patients were then followed with CT and blood tests every 2 months for 6 months
      and every 3 months thereafter. RESULTS: Four tumors required 1 radio frequency
      delivery and 1 required 2 applications during the same session. No complications
      were encountered except for a subcapsular hematoma in 1 patient, which resolved
      spontaneously. Two patients experienced transient hematuria. Of the patients 4
      were discharged from the hospital after 2 days and 1 after 1 day. After 6 to 18
      months (median 9) all patients were tumor-free on CT without suppress additional
      treatment. CONCLUSIONS: In this small preliminary study radio frequency ablation
      of small peripheral renal cell carcinomas appears to be a feasible, safe and
      promising technique.

PMID- 11956418
TI  - Urinary stone risk factors in the siblings of patients with calcium renal stones.
AB  - PURPOSE: We determined which, if any, urinary stone risk factors accurately
      discriminate stone forming and nonstone forming siblings of patients with calcium
      renal stones. MATERIALS AND METHODS: A total of 252 siblings of stone formers
      provided 2, 24-hour urine samples, which were sent overnight and analyzed at a
      central laboratory. Standard stone risk factors were measured and the
      supersaturation of calcium oxalate, calcium phosphate and uric acid was
      calculated. RESULTS: Discriminant functions were derived for each gender by
      multivariate analysis. In stone forming sisters higher urinary calcium and pH
      discriminated with a success rate of 70%. In stone forming brothers higher
      urinary calcium, lower urinary potassium and older age discriminated with a
      success rate of 79%. CONCLUSIONS: Select urinary measurements as well as age
      classify siblings into those with and without stones with fair accuracy. Calcium
      excretion and urinary pH in females, and calcium excretion, urinary potassium and
      age in males are feasible identifiers of stone forming siblings. To determine
      whether these measurements can be used to predict new stone onset may require
      years of observation of our current cohort.

PMID- 11956419
TI  - Computerized tomography attenuation value of renal calculus: can it predict
      successful fragmentation of the calculus by extracorporeal shock wave
      lithotripsy? A preliminary study.
AB  - PURPOSE: We evaluated the attenuation value of renal calculi on unenhanced axial
      computerized tomography (CT) images as a predictor of calculous fragmentation by
      extracorporeal shockwave lithotripsy (ESWL) (Dornier Medical Systems, Inc.,
      Marietta, Georgia). MATERIALS AND METHODS: We included 30 patients with renal
      calculi up to 20 mm. in this prospective study. Calculous attenuation value was
      measured in Hounsfield units on unenhanced CT sections through the calculi.
      Patients were subsequently treated with ESWL. RESULTS: Patients were grouped
      according to calculous attenuation value as groups 1-less than 500, 2-500 to
      1,000 and 3-greater than 1,000 Hounsfield units. Of the 30 patients 24 (80%)
      underwent successful treatment. The rate of stone clearance was 100% (12 of 12
      cases) in group 1, 85.7% (6 of 7) in group 2 and 54.5% (6 of 11) in group 3. The
      success rate for stones with an attenuation value of greater than 1,000
      Hounsfield units was significantly lower than that for stones with a value of
      less than 1,000 Hounsfield units (6 of 11 versus 18 of 19 cases, chi-square 7.07,
      p <0.01). Patients in group 3 required a greater median number of shock waves for
      stone fragmentation than those in groups 1 and 2 (7,300, 2,500, and 3,390,
      respectively). The mean attenuation value and number of shock waves required for
      calculous fragmentation correlated significantly (r = 0.779, p <0.001).
      CONCLUSIONS: The CT attenuation value of renal calculi can help to differentiate
      stones that are likely to fragment easily on ESWL from those that would require a
      greater number of shock waves for fragmentation or may fail to fragment on ESWL.

PMID- 11956420
TI  - Treatment of proximal ureteral calculi: holmium:YAG laser ureterolithotripsy
      versus extracorporeal shock wave lithotripsy.
AB  - PURPOSE: We compared the safety and efficacy of ureteroscopy with intracorporeal
      holmium:YAG laser lithotripsy and extracorporeal shock wave lithotripsy (ESWL)
      (Dornier Medical Systems, Inc., Marietta, Georgia) for proximal ureteral calculi.
      MATERIALS AND METHODS: A total of 67 patients underwent 81 primary procedures,
      including in situ ESWL with a DoLi 50 lithotriptor (Dornier Medical Systems,
      Inc.) or ureteroscopy combined with holmium:YAG laser lithotripsy for proximal
      ureteral calculi. RESULTS: Of the primary procedures 81 involved proximal
      ureteral calculi, including 35 done for calculi 1 cm. or greater. The initial
      stone-free rate in patients with calculi 1 cm. or greater was 93% for
      ureteroscopy combined with holmium:YAG laser lithotripsy and 50% for in situ
      ESWL. The efficiency quotient for treating proximal ureteral calculi 1 cm. or
      greater was calculated as 0.76 for ureteroscopic lithotripsy and 0.43 for ESWL.
      For proximal ureteral calculi less than 1 cm. the initial stone-free rate was
      100% and 80% for ureteroscopic laser lithotripsy and ESWL, respectively. The
      efficiency quotient was calculated as 0.81 for ureteroscopic lithotripsy and 0.72
      for ESWL for treating proximal ureteral calculi less than 1 cm. There were no
      major complications in either group and all procedures were performed on an
      outpatient basis. CONCLUSIONS: Our study demonstrates that ureteroscopy combined
      with holmium:YAG laser lithotripsy is an acceptable treatment modality for all
      proximal ureteral calculi and excellent results are achieved for calculi 1 cm. or
      larger. Although the stone-free rate was better for smaller stones with
      ureteroscopic laser lithotripsy, efficiency quotients were similar. Therefore,
      ESWL should remain first line therapy for proximal ureteral calculi less than 1
      cm. because of less morbidity, and a lesser anesthesia and analgesic requirement.

PMID- 11956421
TI  - Is ureteral stenting necessary after uncomplicated ureteroscopic lithotripsy? A
      prospective, randomized controlled trial.
AB  - PURPOSE: We conducted a prospective, randomized controlled study to investigate
      the advantages and disadvantages of ureteral stenting after ureteroscopic
      lithotripsy. MATERIALS AND METHODS: A total of 60 patients who underwent
      ureteroscopic lithotripsy were equally randomized into a stented or a nonstented
      group. The inclusion criteria were stone 6 to 10 mm., absence of polyp or
      stricture in the ureter and no mucosal injury during ureteroscopy. The operation
      was performed with a 6Fr rigid ureteroscope without ureteral dilation and stones
      were fragmented with a 1.9Fr electrohydraulic lithotriptor without extraction. A
      7Fr double pigtail stent was placed in the stented group for 3 days after
      ureteroscopy. Urinalysis, plain x-ray and renosonography were performed before
      and after lithotripsy in each patient. Subjective symptoms and pain score were
      recorded on admission to the hospital and 3 days postoperatively. RESULTS: The
      stone-free rate was 100% in each group and preoperative hydronephrosis equally
      resolved in both groups. Mean pain score plus or minus standard deviation
      improved significantly in the nonstented (6.33 +/- 1.81 preoperatively to 2.30 +/
      1.93 postoperatively, paired Student's t test p <0.0001) and stented (7.10 +/-
      1.03 to 2.30 +/- 2.22, p < 0.0001) group. There was no statistical difference in
      pain reduction between the 2 groups (p = 0.18). The amount of extra parenteral
      analgesic used was similar in both groups. One patient in the nonstented group
      visited the emergency room for postoperative renal colic, 25 (83.3%) patients in
      the stented group complained of at least 1 irritative bladder symptom and only 4
      (13.3%) in the nonstented group experienced bladder discomfort. CONCLUSIONS:
      After uncomplicated ureteroscopic electrohydraulic lithotripsy patients without
      ureteral stenting tend to have similar renal function recovery and satisfactory
      pain reduction with less irritative symptoms compared to those treated with a
      ureteral stent. We suggest that it is not necessary to place a ureteral stent
      routinely after uncomplicated ureteroscopic electrohydraulic lithotripsy for
      stones smaller than 1 cm.

PMID- 11956422
TI  - A randomized outcomes trial of ureteral stents for extracorporeal shock wave
      lithotripsy of solitary kidney or proximal ureteral stones.
AB  - PURPOSE: Routine use of ureteral stents before extracorporeal shock wave
      lithotripsy of kidney stones between 10 and 20 mm. is controversial. We conducted
      a prospective randomized clinical trial to evaluate the outcome of ureteral
      stents for treating solitary kidney stones between 10 and 20 mm. or solitary
      proximal ureteral stones less than 20 mm. with shock wave lithotripsy. MATERIALS
      AND METHODS: A total of 97 patients who met the aforementioned criteria were
      randomized between March 1994 to July 1997 into group 1-no stent, group 2-a 4.7Fr
      multi-length stent and group 3-a 7Fr multi-length stent. The patients were
      treated with the Dornier HM3 lithotriptor (Dornier Medical Systems, Inc.,
      Marietta, Georgia) and monitored for stone-free rate, number of days lost from
      work, number of patients requiring rehospitalization, emergency room visits,
      irritative voiding symptom score and pain symptom score. RESULTS: Objective
      outcome was obtained from 91 patients based on a followup of at least 3 months.
      The overall stone-free rate was 80%, with a re-treatment rate of 7%. The number
      of days lost from work was approximately 2, with no significant differences among
      individual groups or subgroups. The hospitalization rate and number of emergency
      room visits in group 1 (22%) were statistically higher compared to groups 2 (7%)
      and 3 (7%). The irritative voiding symptom score was statistically higher in the
      stented groups 2 and 3 compared to the nonstented group 1. CONCLUSIONS: Although
      ureteral stents are associated with more irritative symptoms, their use resulted
      in fewer hospital readmissions and emergency room visits compared to when no
      stent was used to treat solitary kidney stones of 10 to 20 mm. or solitary
      proximal ureteral stones less than 20 mm. Size 4.7Fr stents may be preferable
      over 7Fr stents when used in conjunction with shock wave lithotripsy.

PMID- 11956423
TI  - Ureteral stenting--an obsolete procedure?

PMID- 11956424
TI  - The Dretler stone cone: a device to prevent ureteral stone migration-the initial
      clinical experience.
AB  - PURPOSE: Retrograde stone migration during ureteroscopic lithotripsy occurs in 5%
      to 40% of proximal and distal ureteral stone cases. This migration increases
      morbidity and the need for auxiliary procedures. The Dretler stone cone
      (Medsource, Norwell, Massachusetts) is a novel device to prevent proximal stone
      migration and facilitate fragment extraction during ureteroscopic lithotripsy. We
      assessed the safety and efficacy of the Dretler stone cone in the clinical
      setting and compared it prospectively with a conventional flat wire basket during
      ureteroscopy for ureteral calculi. MATERIALS AND METHODS: To our knowledge we
      report the initial clinical use of the Dretler stone cone in 50 consecutive
      patients with ureteral calculi undergoing ureteroscopic extraction. Calculi were
      situated above the sacroiliac joint in 24 cases, over the sacroiliac joint in 15
      and below the sacroiliac joint in 11. Pneumatic lithotripsy was done in 42 cases.
      In the remaining 8 cases ureteroscopic (3) or fluoroscopic (5) intact stone
      extraction was performed. The later 23 cases using the Dretler stone cone were
      prospectively compared with 20 of ureteroscopic intracorporeal lithotripsy using
      a standard flat wire basket. RESULTS: The Dretler stone cone was successfully
      placed in all 50 cases. In 41 patients it was placed via cystoscopy under
      fluoroscopic guidance, while 9 impacted stones required ureteroscopic placement.
      Six patients in whom the Dretler stone cone was used had residual fragments less
      than 3 mm. No patient required auxiliary procedures. In the prospective trial no
      patients in Dretler stone cone group had residual fragments greater than 3 mm. or
      required auxiliary procedures. However, in the flat wire basket group residual
      stones greater than 3 mm. were present in 6 cases (30%, p <0.001), while
      auxiliary procedures were required in 4 (20%, p <0.01). CONCLUSIONS: The Dretler
      stone cone represents a new generation of basketry that minimizes proximal
      ureteral stone migration and allows safe extraction of fragments during
      ureteroscopic lithotripsy. In our experience it is associated with a lower
      incidence of significant residual fragments and fewer auxiliary procedures than
      conventional flat wire baskets.

PMID- 11956425
TI  - Comparison of hand assisted versus standard laparoscopic radical nephrectomy for
      suspected renal cell carcinoma.
AB  - PURPOSE: We compared standard and hand assisted laparoscopic radical nephrectomy
      for suspected renal cell carcinoma. MATERIALS AND METHODS: We retrospectively
      reviewed 22 hand assisted and 16 standard laparoscopic radical nephrectomies
      performed for suspected renal cell carcinoma. Operative and recovery data were
      collected prospectively and from medical records as part of an institutional
      review board approved protocol. Patients completed pain, activity and the 12-item
      short form health related quality of life surveys preoperatively and
      postoperatively. RESULTS: Although patients undergoing hand assisted laparoscopic
      nephrectomy had larger tumors (mean 6.3 versus 4.1 cm., p = 0.009), tended toward
      greater corrected mean specimen weight (658 versus 482 gm., p = 0.111) and had
      greater medical co-morbidity (p = 0.0228), mean operative time for hand assisted
      laparoscopic procedures was significantly shorter (205 versus 270 minutes, p =
      0.0004). With experience mean operative time decreased for standard but not for
      hand assisted laparoscopy (293 to 232 minutes, p = 0.0445, versus 206 to 204, p =
      0.6162). Procedure type, surgeon experience and adrenal sparing were the only
      significant predictors of operative time. There was no difference in the groups
      in terms of the complication rate, hospital cost or stay, return to activity or
      overall pain score, or in the difference in preoperative and postoperative 12
      item short form scores. Hand assisted laparoscopic nephrectomy tended to be
      associated with more abdominal pain early in convalescence and more wound
      complications but not significantly so. CONCLUSIONS: Hand assisted laparoscopic
      radical nephrectomy offers recovery, morbidity and cost that are comparable to
      those of standard laparoscopy. The benefits of the technique include shorter
      operative times, no need for specimen morcellation and direct manual control of
      the operative field. It is particularly useful early in surgeon experience, for
      large specimens or when patient co-morbidities require a rapid procedure.

PMID- 11956426
TI  - Phase I trial of a B7-1 (CD80) gene modified autologous tumor cell vaccine in
      combination with systemic interleukin-2 in patients with metastatic renal cell
      carcinoma.
AB  - PURPOSE: A reason that the immune system may fail to reject tumors is that T
      cells encounter tumor antigen derived peptides on the surface of tumor cells in a
      tolerizing rather than activating context since tumor cells do not express T cell
      co-stimulatory molecules such as B7-1 (CD80). In preclinical models over
      expression of B7-1 on the surface of tumor cells has been shown to activate T
      cells which kill tumor cells. We conducted a phase I clinical trial testing this
      approach in patients with metastatic renal cell carcinoma. MATERIALS AND METHODS:
      Resected tumors from 15 patients were disaggregated and adapted to tissue
      culture, transduced with the B7-1 gene and injected subcutaneously as a vaccine.
      The dose of the vaccine was escalated in 3 separate cohorts of patients, and
      systemic interleukin-2 (IL-2) was administered as an adjuvant designed to enhance
      the proliferation of the vaccine activated T cells. RESULTS: Of the 15 patients 9
      had measurable disease, 2 had a partial response and 2 had stable disease.
      Perivascular T cell infiltrates at autologous tumor delayed type hypersensitivity
      skin test sites developed in 3 of the 4 patients with stable disease or partial
      response. Although the patients experienced the usual and expected toxicity from
      the IL-2, there was no significant toxicity observed with the vaccine.
      CONCLUSIONS: The B7-1 gene modified autologous tumor cell vaccine is safe and can
      be combined with systemic IL-2 with acceptable toxicity. Immunological and
      clinical responses were observed in some of the patients. A phase II trial is
      reasonable to determine the efficacy of this approach.

PMID- 11956427
TI  - A comparison of BTA stat, hemoglobin dipstick, telomerase and Vysis UroVysion
      assays for the detection of urothelial carcinoma in urine.
AB  - PURPOSE: We determine the sensitivity and specificity of various assays for the
      detection of urothelial carcinoma. MATERIALS AND METHODS: A total of 280 voided
      urine specimens from 265 patients were obtained immediately before cystoscopy for
      BTA stat, (Bard Diagnostic, Redmond, Washington) hemoglobin dipstick, (Bayer,
      Elkhart, Indiana) telomerase and UroVysion (Vysis, a wholly owned subsidiary of
      Abbott Laboratories, Abbott Park, Illinois) analysis. RESULTS: Of the 265
      patients 75 had biopsy proven urothelial carcinoma, and the sensitivity of the
      assays was determined from these patients. From most sensitive to least
      sensitive, the overall sensitivity of UroVysion (73 cases), BTA stat (72),
      hemoglobin dipstick (73) and telomerase (70) was 81%, 78%, 74%, and 46%,
      respectively. Each of the first 3 tests was statistically significantly more
      sensitive than the telomerase assay (p <0.05). However, the differences in
      overall sensitivity of UroVysion, BTA stat and hemoglobin dipstick were not
      statistically significant. The specificity of the tests was calculated for 80 of
      the 265 patients in this study who had no history of urothelial carcinoma and
      negative cystoscopy findings despite common urological complaints. From most
      specific to least specific, the specificity of UroVysion, telomerase, BTA stat
      and hemoglobin dipstick was 96%, 91%, 74% and 51%, respectively. UroVysion and
      telomerase were statistically significantly (p <0.01) more specific than the BTA
      stat and hemoglobin dipstick assays, and all of the assays were more specific
      than hemoglobin dipstick testing (p <0.001). CONCLUSIONS: Our study reveals that
      UroVysion is the most sensitive and specific assay among those tested for the
      detection of urothelial carcinoma. Telomerase testing had good specificity but
      poor sensitivity. The BTA stat and hemoglobin dipstick tests had good sensitivity
      but relatively poor specificity. UroVysion is a promising new assay for the
      detection of urothelial carcinoma in urine specimens. However, further studies
      are needed to explore the role of the various assays in the treatment of patients
      with superficial urothelial carcinoma.

PMID- 11956428
TI  - Clinical panurothelial disease in patients with superficial bladder tumors:
      therapeutic implications.
AB  - PURPOSE: We established the prognostic and therapeutic implications of
      panurothelial involvement in patients with superficial bladder tumors for
      optimizing therapeutic approaches in those at risk for panurothelial involvement.
      MATERIALS AND METHODS: We studied the records of 35 patients with clinical
      panurothelial disease. Since all of these patients presented with high risk
      superficial bladder cancer during followup, they were included in specific
      therapeutic and followup regimens. Radical procedures or conservative therapies
      were indicated mainly according to pathological examination and the recurrence
      pattern. RESULTS: Panurothelial involvement was a late stage of a recurrent and
      diffuse process that essentially developed in sequences, in which all patients
      presented with high risk superficial bladder tumors. This process involved
      continued relapse after panurothelial involvement developed. Notably 19 patients
      (79.1%) at risk for recurrence had repeat relapse in the urothelium. In the upper
      urinary tract 12 patients (34.3%) had bilateral involvement, including 7 (41.2%)
      of 17 patients after cystectomy. We identified 2 subgroups of patients. The
      subgroup with a better prognosis included 27 patients in whom late panurothelial
      disease developed step by step after a complete response to intravesical therapy,
      including 14 (51.8%) who were free of disease. The other subgroup with a poor
      prognosis included 8 patients with concurrent bladder carcinoma in situ and
      prostate involvement as well as early panurothelial disease, of whom only 2 (25%)
      were disease-free. All patients underwent many therapeutic approaches. A mean of
      7.5 surgical procedures per patient were done, including a mean of 5.5
      transurethral resections, a mean of 1 conservative approach to the upper urinary
      tract and a mean of 1.1 radical procedures. At a median followup of 111 months 10
      patients (28.5%) were disease-free but only 7 (20%) retained the bladder, while
      19 (54.3%) died of tumor. CONCLUSIONS: Patients with high risk superficial
      bladder multifocal tumors and associated bladder carcinoma in situ are at high
      risk for panurothelial involvement. Radical cystectomy may be recommended in
      these patients when initially or during followup, concurrent high risk
      superficial bladder tumors and prostate involvement develop or prostate
      involvement recurs. For the upper urinary tract conservative therapies may be
      advisable when noninfiltrating tumors are diagnosed even after cystectomy due to
      the high rate of bilateral new onset disease. When cystectomy is performed,
      extended excision of the upper urinary tract and pyelo-intestinal anastomosis may
      be considered.

PMID- 11956429
TI  - Analysis of early complications after radical cystectomy: results of a
      collaborative care pathway.
AB  - PURPOSE: We examined our recent series of patients who underwent radical
      cystectomy to determine and analyze the early perioperative morbidity of the
      procedure in a contemporary series treated with the guidance of a clinical
      pathway. MATERIALS AND METHODS: We reviewed the records of 304 consecutive
      patients who underwent radical cystectomy from December 1995 to July 2000. We
      specifically evaluated complications that developed within 30 days of the
      procedure. Potential variables predictive of early morbidity were analyzed,
      including patient age, gender, race, American Society of Anesthesiologists score,
      type of urinary diversion, smoking history, estimated blood loss, transfusion
      requirement, pathological stage and operative time. RESULTS: The overall minor
      complication rate was 30.9% (94 of 304 patients). Postoperative ileus was the
      most common minor complication, affecting 54 patients (18%). Increased blood loss
      and major complications predicted a significantly higher likelihood of ileus on
      multivariate analysis (p = 0.02 and 0.001, respectively). Major complications in
      15 patients (4.9%) correlated with higher American Society of Anesthesiologists
      score, surgical intensive care unit admission and transfusion requirement (p =
      0.01, <0.001 and 0.001, respectively). The early mortality rate was 0.3% (1
      patient). CONCLUSIONS: Within the framework of a clinical pathway, radical
      cystectomy can be performed safely with an acceptable rate of early minor and
      major complications. Delay in the return of bowel function is the most common
      minor complication. Increased estimated blood loss, transfusion requirement and a
      major complication predicted a higher likelihood of postoperative ileus. The
      acceptable rate of early morbidity in this series in a 5-year period validates
      its use in patients undergoing radical cystectomy.

PMID- 11956430
TI  - Comparative analysis of complexed prostate specific antigen, free prostate
      specific antigen and their ratio in detecting prostate cancer.
AB  - PURPOSE: We evaluate the diagnostic use of total, free and complexed serum
      prostate specific antigen (PSA), and their ratios for enhancing the specificity
      in detecting prostate cancer. MATERIALS AND METHODS: A total of 354
      nonconsecutive men undergoing prostate biopsy were eligible for this
      retrospective and prospective study. Cancer was found in 122 of these 354 men
      (34%). Receiver operating characteristics curve analyses were used to calculate
      and compare the performance of total PSA (Hybritech, San Diego California and
      Bayer, Tarrytown, New York), complexed PSA (Bayer), percent complexed PSA and
      percent free PSA. In addition, sensitivity and specificity were calculated and
      compared. RESULTS: The area under the receiver operating characteristics curve
      was highest for percent free PSA, followed by percent complexed PSA, complexed
      PSA and the 2 total PSA assays (Hybritech and Bayer). The cutoff value of 3.45
      ng./ml. for complexed PSA detected the same number of cancers and resulted in 1
      additional false-positive case compared with a Hybritech total PSA threshold of
      4.0 ng./ml. At sensitivities of 80% to 95%, there were no significant differences
      for detection comparing the corresponding specificities between Hybritech total
      PSA and complexed PSA for all 354 men. Complexed PSA alone did not enhance the
      overall diagnostic accuracy compared with percent free PSA in the Hybritech total
      PSA range between 4.01 and 6.00 ng./ml., between 6.01 and 10.00 ng./ml., and
      between 2.50 and 6.00 ng./ml. At sensitivities of 80% to 95% specificity of
      percent complexed PSA was almost identical to that of percent free PSA except for
      the Hybritech total PSA range less than or equal to 4.00 ng./ml. CONCLUSIONS:
      This study suggests complexed PSA is equivalent to total PSA for the early
      detection of prostate cancer. Percent free PSA outperforms complexed PSA and
      percent complexed PSA performed equivalently to percent free PSA in all total PSA
      ranges analyzed between 2.5 and 10 ng./ml.

PMID- 11956431
TI  - Lower prostate specific antigen outcome than expected following radical
      prostatectomy in patients with high grade prostate and a prostatic specific
      antigen level of 4 ng/ml. Or less.
AB  - PURPOSE: We report the estimates of 10-year prostate specific antigen (PSA)
      outcome following radical prostatectomy in patients with or without grade 4 or 5
      disease in the needle biopsy or prostatectomy specimen stratified by the
      presenting PSA level. MATERIALS AND METHODS: From 1989 to 2001, 2,254 patients
      treated with radical prostatectomy for clinically localized prostate cancer
      comprised the study cohort. PSA outcome was estimated using the actuarial method
      of Kaplan and Meier, and was stratified by the presenting PSA level and needle
      biopsy and prostatectomy Gleason score. RESULTS: The 10-year estimates of PSA
      outcome declined significantly (p </=0.002) for patients with biopsy or
      prostatectomy Gleason score 6 or less as the presenting PSA level increased. This
      trend was observed for biopsy and prostatectomy Gleason score 7 or higher except
      for the PSA 4 or less group which did significantly worse (46% versus 62%, p =
      0.03) compared to the PSA greater than 4 to 10 ng./ml. group. This finding may be
      explained by a low serum free testosterone level and the presence of a
      significantly higher proportion of prostatectomy Gleason score 8 to 10 disease
      (25% versus 16%, p = 0.03) in the PSA 4 or less versus greater than 4 to 10
      ng./ml. group. CONCLUSIONS: Patients with Gleason grade 4 or 5 disease in the
      radical prostatectomy specimen and a presenting PSA of 4 ng./ml. or less may be
      androgen deficient and have a significantly lower estimate of 10-year PSA outcome
      then expected based on the presenting PSA level.

PMID- 11956432
TI  - Percent of cancer in the biopsy set predicts pathological findings after
      prostatectomy.
AB  - PURPOSE: The ability to use pretreatment variables to identify patients with
      organ confined prostate cancer continues to challenge physicians. We examined
      information available preoperatively, including prostate needle biopsy, clinical
      stage and preoperative prostate specific antigen (PSA), and evaluated these data
      based on pathological variables after radical retropubic prostatectomy. MATERIALS
      AND METHODS: We reviewed results in 135 consecutive patients who underwent
      radical retropubic prostatectomy at a single institution. Needle biopsy
      information, such as the number of cores, percent of tumor per biopsy set,
      laterality of positive cores and Gleason sum, were compared with pathological
      data on the radical retropubic prostatectomy specimen, including pathological
      stage, Gleason sum and tumor volume. Clinical data, including biopsy information
      and pathological findings, were compared using univariate and multivariate
      models. RESULTS: Overall total PSA, percent of tumor in the biopsy and bilateral
      positive cores directly correlated with tumor volume (p <0.01). Also, increasing
      PSA, increasing percent of tumor in the biopsy and bilateral positive cores were
      associated with increased risks of extracapsular extension (p <0.01).
      CONCLUSIONS: From the information readily available from prostate needle biopsy
      these results suggest that percent of tumor in the biopsy is a useful predictor
      of pathological stage and tumor volume. Furthermore, including percent of tumor
      in the biopsy set and bilateral disease with traditional variables such as serum
      PSA and clinical stage may improve pretreatment tumor staging. This finding adds
      additional credence to the inclusion of percent of tumor in the biopsy set in
      models for the preoperative prediction of pathological stage and should be
      factored into discussions with patients on treatment options.

PMID- 11956433
TI  - Determination of prognosis in patients with prostate cancer treated with radical
      prostatectomy: prognostic value of CD44v6 score.
AB  - PURPOSE: A third of the patients treated with radical prostatectomy experience
      progression even when tumors are confined pathologically to the prostate. CD44
      may be a promising prognostic marker for determining malignant potential.
      However, there has not been a standard scoring system because of its
      heterogeneous staining pattern. Thus, we developed an objective scoring system to
      evaluate reliably CD44v6 (Bender Medsystems, Vienna, Austria) as a prognostic
      marker for prostate cancer. MATERIALS AND METHODS: A total of 22 patients with
      metastatic stage pT3bN0M0 or any pTN1M0 disease and 18 with nonmetastatic disease
      less than stage pT3bN0M0 were selected from a well examined group of 114 who
      underwent radical retropubic prostatectomy. Mean followup was 33 months (range 4
      to 78). A combined CD44v6 score was determined by adding the scores of the
      primary and secondary areas. CD44v6 expression in terms of the CD44v6 score in
      primary and metastatic tissues was examined. The relationships of CD44v6
      expression with pathological stage, progression and PSA-free survival were also
      evaluated. The prognostic value of the CD44v6 score for progression was analyzed
      by multivariate analysis. RESULTS: Progression in the metastatic group was
      significantly higher than in the nonmetastatic group (p <0.0001). CD44v6
      expression of the primary tumors differed significantly in the 2 groups (p =
      0.014). The CD44v6 score in primary tumor tissues inversely correlated with
      pathological stage (p = 0.004) and progression (p = 0.035), and positively
      correlated with PSA-free survival (p = 0.041). Furthermore, patients in the
      nonmetastatic group with a CD44v6 score of greater than 75 (cutoff value) had a
      significantly better prognosis (log rank test p = 0.0022), while those with a
      CD44v6 score of less than 75 had a prognosis similar to those in the metastatic
      group. On multivariate analysis pathological stage and surgical margin positivity
      were independent factors for progression but the CD44v6 score was not.
      CONCLUSIONS: According to our results the suggested CD44v6 score system is
      useful. A CD44v6 score of less than 75 may be a predictor of poor prognosis in
      the nonmetastatic group and this property may have potential application for
      planning adjuvant therapy.

PMID- 11956434
TI  - Urethral extensibility applied to reconstructive surgery.
AB  - PURPOSE: The human male urethra has great capacity to extend under traction. This
      extensibility is the principle of some surgical techniques used to overcome
      urethral defects and for penile lengthening. However, to our knowledge safe
      limits of urethral extensibility in reconstructive surgery have not been yet
      established by a morphological study. To this end we measured fresh human
      cadaveric urethras with and without traction. MATERIALS AND METHODS: We analyzed
      the macroscopically normal, fresh cadaveric urethra from 25 men 6 months to 73
      years old at death (mean age 30.6). Penile length and length of the total,
      penile, bulbar and membranous urethra were measured. Length under maximal
      constant traction and the maximal stretched length without penile curvature at
      artificial erection were determined. Extensibility is expressed as the percent of
      the variation in initial length at rest and maximal constant traction length.
      Maximal stretched length without penile curvature at artificial erection is
      expressed as a percent of maximal constant traction length. RESULTS: Total
      urethral extensibility was higher than penile extensibility (p <0.001). Urethral
      extensibility decreased with aging (r = -0.806, p <0.001). Mean extensibility of
      the whole male urethra was 66.2% +/- 7.2% and differences among urethral segments
      were not significant (p = 0.283). Mean maximal stretched length without penile
      curvature at artificial erection was 75.2% +/- 3.8% and it did not change with
      age. CONCLUSIONS: Knowledge of the safe anatomical limit of urethral
      extensibility applied to reconstructive surgery may avoid complications and the
      necessity for more complex techniques. This limit should be approximately 75% of
      the maximal constant traction length or a gap-to-normal urethra ratio of 1:4.
      However, age related variations should be considered.

PMID- 11956436
TI  - Fluoroscopy guided retrograde ureteral stent insertion in patients with a
      ureteroileal urinary conduit: method and results.
AB  - PURPOSE: We evaluated retrograde double pigtail stent placement in patients with
      ureteroileal anastomosis. MATERIALS AND METHODS: Procedures were performed under
      digital C-arm fluoroscopic guidance and the patient under sedation analgesia.
      Radiography of the conduit was done to delineate urinary diversion anatomy and
      identify ureteral reflux. A purpose designed, angled tip catheter was used to
      direct a straight glide wire across the ureteroileal anastomosis. The glide wire
      was exchanged for a stiff guide wire for stent placement. We retrospectively
      evaluated the clinical records of 7 men and 5 women with a mean age of 54.3 years
      in a 7-year period. In 11 patients a new stent was placed because of ureteroileal
      stricture in 5, anastomotic leakage in 3, ureterolithiasis in 2 and recurrent
      malignancy in 1. RESULTS: New stent placement was successful in 10 of the 11
      patients (90.9%, 13 of 16 ureters or 81.3%). Stent placement was successful in
      the 8 ureters in which reflux was noted on radiography of the conduit and in 5 of
      the 9 (55.6%) in which no reflux was noted. Stent replacement was accomplished in
      all 22 ureters (6 patients) in which it was attempted. Mean radiological
      screening time for new stent placement was 13.3 minutes (range 4.7 to 19.7),
      while for exchange it was 6.4 minutes (range 0.8 to 15.1). There were no
      immediate complications. CONCLUSIONS: This technique represents a useful approach
      to the ureter and should be considered an alternative to percutaneous nephrostomy
      and surgical revision. The approach is also useful for other ureteral procedures,
      including stone or migrated stent retrieval.

PMID- 11956435
TI  - Usefulness of 3-dimensional reconstructed images of renal arteries using
      rotational digital subtraction angiography.
AB  - PURPOSE: We assess the feasibility of a 3-dimensional (D) reconstruction
      technique of rotational digital subtraction angiography (DSA) for visualization
      of the renal arteries. MATERIALS AND METHODS: We evaluated 28 kidneys in 20
      patients. Rotational DSA images were obtained during a deep inspiratory pause
      after contrast material injection through the renal artery. Acquired data were
      transferred to an image workstation and reconstructed as 3-D images. Visibility
      of the main trunk of the renal artery, segmental arteries, interlobar arteries
      and arcuate arteries was classified as grade 4-excellent, grade 3-good, grade 2
      satisfactory and grade 1-poor. The 3-D reconstructed images were compared with
      conventional 2-D DSA performed just before the rotational DSA. The criteria for
      evaluation were visibility of the aneurysm neck in 8 cases of aneurysm,
      delineation of the feeding arteries in 6 cases of renal lesions and visibility of
      the relationship between renal branches in other cases. RESULTS: Delineation of
      grades 4 to 1 was 93%, 7%, 0% and 0% for the main renal artery, 66%, 21%, 7% and
      6% for segmental arteries, 61%, 11%, 21% and 7% for interlobar arteries, and 36%,
      18%, 36% and 10% for arcuate arteries, respectively. The 3-D images had the
      advantage over 2-D DSA in 75% of cases. In all cases of aneurysm 3-D images were
      obviously more useful than 2-D DSA. CONCLUSIONS: 3-D images of renal arteries
      obtained with rotational DSA are considered acceptable for clinical use.

PMID- 11956437
TI  - Long-term voiding pattern of patients with ileal orthotopic bladder substitutes.
AB  - PURPOSE: Good long-term functional outcome of orthotopic bladder substitution
      will ultimately decide whether it is here to stay. Therefore, we analyzed
      exclusively voiding patterns of long-term survivors with an orthotopic ileal
      bladder substitute. MATERIALS AND METHODS: In all patients with an ileal
      orthotopic bladder substitute day and nighttime continence status, voiding
      frequency, bladder capacity and pad usage were prospectively assessed by
      frequency volume charts and a standardized questionnaire. All men surviving 5 or
      more years with a median followup of 95 months (range 60-132) were evaluated.
      RESULTS: Spontaneous voiding was possible in 82 of 86 (95.3%) evaluable patients
      after catheter removal. Daytime continence increased from 61% after 3 months to
      92% at 12 months and remained stable throughout the following 4 years yet
      decreased slightly thereafter. Nocturnal continence rates were 10% to 15% lower
      throughout the study period. Functional reservoir capacity averaged 473 ml. after
      12 months and did not change in subsequent years. After a decrease during the
      first 12 months, daytime frequency (4.1 to 4.8 times daily) and nocturia (1.8 to
      2.3 a night) did not change in the next decade. Patient age at surgery was an
      important determinant for long-term reservoir capacity, nocturia and continence
      status. CONCLUSIONS: These data provide evidence for good long-term functional
      outcome following orthotopic ileal bladder substitution up to 11 years. We
      attribute the sustained ability to void to the relatively small reservoir size,
      which is made of 40 to 44 cm. of ileum, the avoidance of any funnel shaped outlet
      but rather a side-to-end intestine-urethral anastomosis as well as lifelong
      meticulous followup.

PMID- 11956438
TI  - Long-term results of ileocecal continent urinary diversion in patients treated
      with and without previous pelvic irradiation.
AB  - PURPOSE: Patients who receive pelvic irradiation may require urinary diversion to
      manage complications resulting from progressive malignancy or radiotherapy. The
      choice of urinary diversion is an important issue and remains controversial. We
      characterized the long-term outcome of urinary diversion with a continent
      ileocecal reservoir in patients who received pelvic irradiation versus those who
      underwent urinary diversion without previous irradiation. MATERIALS AND METHODS:
      Continent urinary diversion with an ileocecal reservoir (Mainz pouch 1) was
      performed in 36 irradiated patients in a 9-year period. Morbidity, mortality, the
      reoperative rate and parameters associated with the surgical procedure were
      determined at a median followup of 57 months. Results were compared with those in
      385 nonirradiated patients who received the same type of continent diversion
      after cystectomy for bladder cancer. RESULTS: Irradiated patients had a
      significantly higher rate of serious complications after ileocecal urinary
      diversion than nonirradiated controls. Continence mechanism failure occurred in
      25% of patients in the irradiated group and 5.7% in nonirradiated patients,
      stomal complications were noted in 38.8% and 10.6%, and ureteral complications
      developed in 22.2% and 6.5%, respectively. CONCLUSIONS: In patients who have
      received pelvic radiotherapy, ileocecal Mainz pouch 1 continent urinary diversion
      is associated with a high rate of serious complications and should be avoided.

PMID- 11956439
TI  - Combined urinary and fecal diversion using a no bowel anastomosis technique.
AB  - PURPOSE: We present the experience at our institution with combined fecal and
      urinary diversion using 3 variations of a no anastomosis technique that avoids
      bowel anastomosis. MATERIALS AND METHODS: The charts of 10 female and 2 male
      patients who underwent the no bowel anastomosis technique were identified and
      reviewed. Information on the etiology of urination and defecation abnormalities,
      surgical resolution, complications, hospital stay and other pertinent aspects of
      management were retrospectively reviewed. RESULTS: Mean patient age was 64 years
      (range 36 to 83). Of the 12 patients 7 had a history of cancer treated with
      external beam radiotherapy, while 4 had neurological disorders with combined
      fecal and urinary incontinence or a history of colostomy. Mean hospital stay was
      14.6 days (range 6 to 31) and mean followup was 26.6 months (range 14 to 52).
      There were no postoperative deaths, although a nonQ wave myocardial infarction
      occurred in 1 patient. CONCLUSIONS: The no anastomosis technique of combined
      diversion is recommended in patients with preexisting or planned diversion of the
      fecal stream. Avoidance of bowel anastomosis makes this technique especially
      advantageous in those with a history of radiotherapy.

PMID- 11956440
TI  - Correction of penile curvature using the 16-dot plication technique: a review of
      132 patients.
AB  - PURPOSE: We review the results of 132 cases of congenital and acquired penile
      curvature corrected with our 16 or 24-dot, minimal tension technique using
      multiple parallel plications performed under papaverine induced erection.
      MATERIALS AND METHODS: Chart and telephone interviews were conducted on 132
      consecutive patients 16 to 79 years old who underwent penile plication between
      December 1995 and November 2000. Patient data as well as outcomes were analyzed.
      RESULTS: We were unable to contact 8 patients. Of the patients 16 had congenital
      penile curvature, including 4 in whom the Nesbit procedure performed elsewhere
      had failed, and 116 had Peyronie's disease, including 8 in whom a previous Nesbit
      procedure had failed. Preoperative complaints included persistent penile pain
      with erection for more than 1 year in 15 of 132 cases, difficult intercourse or
      partner discomfort in 106 and poor self-image in 11. Curvature ranged from 30 to
      120 degrees. Erections were evaluated preoperatively with duplex ultrasound after
      intracavernous injection and self-stimulation. Of the patients 63% had good
      erections, 25% moderate erections requiring sildenafil and 12% poor erections
      requiring injection therapy. Foreskin edema necessitating subsequent circumcision
      and an organized hematoma requiring evacuation occurred in 1 case each. At 6
      months 93% of patients reported straight erections and 7% reported almost
      straight but acceptable erections. Recurrence of curvature was reported by 15% of
      patients at a mean of 2.6 years of followup. Four patients reported worsening of
      erectile function after the procedure. CONCLUSIONS: Penile plication is a simple,
      safe method to correct congenital and acquired penile curvature. Using a minimal
      tension parallel plication technique, excellent durable results can be attained.
      This simplified repair avoids the neurovascular bundles and has a minimal to no
      detrimental affect on erectile function. Preoperative counseling must be given
      regarding penile shortening and the palpable small bumps from the nonabsorbable
      sutures.

PMID- 11956441
TI  - Long-term results of plaque thinning with carbide burs, small incisions and
      venous grafting for correcting complex penile curvature in Peyronie's disease:
      poor results of an "ideal" approach.
AB  - PURPOSE: We evaluated the long-term results of plaque thinning by carbide burs,
      small transverse incisions and venous grafting for correcting complex penile
      curvature in patients with Peyronie's disease. MATERIALS AND METHODS: A total of
      13 patients with Peyronie's disease and complex penile curvature received plaque
      thinning by carbide burs equipped with a fraise, small plaque incision and venous
      grafting. All patients were available for long-term followup at a mean of 29
      months. Preoperatively the mean dorsal curvature angle was 73 degrees with an
      additional malrotation in 4 patients. Followup consisted of a standardized
      interview and 3-dimensional photo documentation during erection. RESULTS:
      Although penile straightening was achieved intraoperatively, dorsal curvature
      (mean 35 degrees) recurred in 8 men, of whom 3 noticed this deterioration after a
      longer period. Penile shortening (mean 3.3 cm.) occurred in 7 patients, and
      decreased rigidity during intercourse occurred in 4. CONCLUSIONS: Hypothetically,
      a combined technique of thinning, incision and grafting seems to be an ideal
      surgical approach for correction of complex penile curvatures in Peyronie's
      disease without plaque excision. Although the penis had been completely
      straightened intraoperatively, severe dorsal curvatures recurred and significant
      penile shortening became obvious in more than half of the patients. Manipulation
      of the plaque may be associated with activation of the disease, with all of the
      risks of recurrence and deterioration. Due to the poor results of the thinning
      procedures, we stopped using this surgical approach and now prefer a combination
      of small incisions and grafting only.

PMID- 11956442
TI  - Treatment of Peyronie's disease.

PMID- 11956443
TI  - Transcorporal artificial urinary sphincter cuff placement in cases requiring
      revision for erosion and urethral atrophy.
AB  - PURPOSE: A distal cuff location is often required in patients undergoing
      artificial urinary sphincter reimplantation after previous erosion or in those
      requiring revision because of urethral atrophy at the original cuff site.
      Dissecting the urethra at a more distal site increases the risk of urethral
      injury and erosion, and often the urethral circumference is so small that a 4 cm.
      cuff is too large. We present a novel technique for distal cuff placement using
      transcorporal dissection that leaves corporal tunica albuginea on the dorsal
      surface of the urethra, allowing for its safer mobilization and adding to its
      bulk. MATERIALS AND METHODS: We reviewed the charts of 31 men who underwent this
      technique and contacted 26 by telephone. The indications for distal transcorporal
      cuff placement varied. In 7 men with inadequate urethral coaptation with a 4 cm.
      proximal cuff at initial implantation a primary transcorporal tandem cuff was
      implanted distal. In 8 men persistent or recurrent incontinence despite a 4 cm.
      proximal cuff led to secondary distal reimplantation. Previous artificial urinary
      sphincter erosion and/or infection in 10 cases, previous urethral surgery at the
      optimal cuff site in 5 and radiation changes at the optimal cuff site in 1 led to
      selection of the more distal site and technique. Of the transcorporally placed
      cuffs 18 were 4 cm. and 13 were 4.5 cm. Preoperatively 5.2 pads were used daily.
      Of the 31 patients 27 were impotent preoperatively, 1 had normal erections, 1 had
      partial erections with the MUSE drug delivery system (Vivus, Inc., Menlo Park,
      California) and 2 had a previously placed penile prosthesis. RESULTS: At a mean
      followup of 17 months 26 of the 31 patients (84%) had occasional or no stress
      incontinence requiring 0 to 1 pad daily, 2 with pure urge incontinence used 1 to
      2 pads daily and 3 had mixed incontinence requiring 0 to 3 pads daily. Of the 26
      men surveyed 25 were very satisfied with the postoperative level of incontinence.
      Postoperatively erectile function deteriorated in 1 patient and was unchanged in
      the remainder. There was no erosion or infection of the transcorporally placed
      cuffs, although 3 were replaced for malfunction. CONCLUSIONS: This technique
      offers significant advantages in cases of revision. The technique protects the
      urethra from intraoperative dissection injury and decreases the risk of erosion
      because the urethra is buttressed at its vulnerable location. In addition, bulk
      is added to the urethra, allowing for better cuff sizing, which is usually a
      problem at this location where the urethra is small, thereby, improving
      continence in revised cases. Our success has recently led us to abandon tandem
      cuff placement altogether. There is a potential for deteriorating erectile
      function in potent men who undergo implantation in this fashion.

PMID- 11956444
TI  - Removal of transurethral catheter during urodynamics may unmask stress urinary
      incontinence.
AB  - PURPOSE: The measurement of Valsalva leak point pressure may have an important
      role in the treatment algorithm of women with stress urinary incontinence.
      However, some patients with stress urinary incontinence may not have leakage
      during standard urodynamic studies and, thus, the Valsalva leak point pressure
      cannot be determined. We hypothesized that the transurethral catheter may inhibit
      leakage during urodynamics. MATERIALS AND METHODS: We evaluated 21 consecutive
      women presenting with complaints of stress urinary incontinence who failed to
      have leakage on urodynamic studies. Bedside cystometry was performed, followed by
      urodynamics using a 6Fr transurethral catheter. When stress urinary incontinence
      was not noted, the catheter was removed and the Valsalva leak point pressure was
      measured using the intraabdominal pressure catheter. RESULTS: No woman had
      leakage on urodynamic studies with the catheter in place, although 11 of 21 had
      leakage after the catheter was removed and 15 had leakage on bedside cystometry.
      All 11 patients with leakage at catheter removal showed leakage on bedside stress
      testing. Mean Valsalva leak point pressure in those with leakage was 67 cm.
      water. CONCLUSIONS: Patients with a history of stress urinary incontinence and
      those with a positive bedside stress test who do not have leakage during a
      Valsalva maneuver on urodynamic studies should repeat the Valsalva maneuver with
      the catheter out. This technique may unmask stress urinary incontinence and allow
      the measurement of Valsalva leak point pressure.

PMID- 11956445
TI  - Diagnosis of female bladder outlet obstruction and relevance of the parameter
      area under the curve of detrusor pressure during voiding: preliminary results.
AB  - PURPOSE: The diagnosis of bladder outlet obstruction in women by pressure flow
      study may be difficult because there are several definitions of bladder outlet
      obstruction, several parameters and no standard cutoffs. We evaluated the ability
      of pressure flow studies to separate women into unobstructed, equivocal and
      obstructed groups. MATERIALS AND METHODS: In a prospective study 85 women with
      lower urinary tract symptoms underwent clinical evaluation, including physical
      examination, voiding cystourethrography, endoscopy, flow rate and post-void
      residual volume measurement. A pressure flow study was performed 15 days later.
      The pressure flow study parameters were maximum flow, post-void residual volume,
      detrusor pressure at maximum flow, vesical pressure at maximum flow, area under
      the curve of detrusor pressure during voiding and area under the curve of
      detrusor pressure during voiding adjusted for voided volume. After considering
      the clinical evaluation 2 urologists classified the patients into 3 groups,
      namely unobstructed, equivocal and obstructed, as the traditional classification.
      Linear discriminant analysis was then performed using the traditional
      classification and pressure flow study data. RESULTS: Mean patient age was 55
      years (range 18 to 83). According to the traditional classification there were 36
      unobstructed, 28 equivocal and 21 obstructed cases. Significant differences were
      noted in all pressure flow study parameters (analysis of variance p <0.05).
      Linear discriminant analysis showed that area under the curve of detrusor
      pressure during voiding adjusted for voided volume was the most statistically
      discriminating parameter. Of the cases 86%, 36% and 57% were identically
      categorized by the traditional and area under the curve of detrusor pressure
      during voiding adjusted for voided volume parameter classifications in the
      unobstructed, equivocal and obstructed groups, respectively. The other pressure
      flow study parameters showed less satisfactory results. CONCLUSIONS: Area under
      the curve of detrusor pressure during voiding adjusted for voided volume appears
      to be the most discriminating urodynamic parameter of female bladder outlet
      obstruction. Other studies are needed to test the reliability and validity of
      this new parameter.

PMID- 11956446
TI  - Urinary incontinence and hysterectomy in a large prospective cohort study in
      American women.
AB  - PURPOSE: We investigated the effects of hysterectomy with and without concomitant
      urinary incontinence repair on incontinence severity in one of the largest
      prospective studies of hysterectomy outcomes performed in the United States.
      MATERIALS AND METHODS: We administered the Urinary Symptoms Scale for Women to
      1,299 women before hysterectomy done for benign conditions, and 6, 12, 18 and 24
      months postoperatively to measure the presence, severity and type of urinary
      incontinence. RESULTS: Before hysterectomy 29.5% of participants had severe
      urinary incontinence, which decreased to 10% 12 and 24 months after hysterectomy.
      Most women with severe incontinence before hysterectomy showed improved
      incontinence 1 year after surgery (89.1%) and were still improved after 2 years
      (86.5%). The majority of women with moderate incontinence before hysterectomy
      showed improved incontinence 1 year after surgery (62.4%) and were still improved
      after 2 years (61.2%). However, some women with mild or no incontinence before
      hysterectomy had new onset incontinence or the condition had worsened 1 year
      after surgery (16.7%) and was still worse after 2 years (14.4%). A concomitant
      urinary incontinence repair procedure significantly increased the probability
      that a woman with severe incontinence would have improved incontinence 1 year
      after hysterectomy and significantly decreased the probability that a woman with
      mild or no incontinence would have worse incontinence after 2 years. CONCLUSIONS:
      The majority of women who undergo hysterectomy for nonmalignant indications
      experienced improved urinary incontinence during the first 2 years after surgery.

PMID- 11956447
TI  - Determinants of patient dissatisfaction after a tension-free vaginal tape
      procedure for urinary incontinence.
AB  - PURPOSE: We identified the determinants of patient satisfaction after a tension
      free vaginal tape procedure. MATERIALS AND METHODS: We retrospectively analyzed
      the records of 187 consecutive women with genuine stress (133) and mixed (54)
      incontinence. The objective cure rate was determined by clinical and urodynamic
      examination, and the subjective cure rate was assessed by a visual analog scale
      and the Contilife questionnaire. RESULTS: Mean followup was 27 months (range 6 to
      34). The overall complication rate was 35.3%. The major perioperative and
      postoperative complications were bladder injury in 9.6% of cases, urinary
      retention in 6.4%, difficult voiding in 10.7% and new onset urge symptoms in
      21.3%. The overall objective and subjective cure rates were 90.4% and 70.6%,
      respectively. The mean preoperative and postoperative visual analog scale score
      plus or minus standard deviation was 6.2 +/- 2.4 and 0.9 +/- 2.2, respectively (p
      = 0.0001). The subjective cure rate was significantly lower in women who
      underwent the procedure under general or spinal anesthesia than in those who
      received local anesthesia (p = 0.01). This difference was related to the rate of
      new onset urge symptoms. The mean postoperative visual analog scale score in
      women with and without new onset urge symptoms was 2.2 +/- 3.2 and 0.2 +/- 0.7,
      respectively (p = 0.0001). No difference in the subjective cure rate was detected
      according to patient age, menopausal status, previous incontinence surgery, the
      body mass index, additional procedures associated with tension-free vaginal tape
      surgery or the Ingelman-Sundberg classification. CONCLUSION: These results
      confirm that the tension-free vaginal tape procedure is associated with a high
      objective but lower subjective cure rate. The procedure performed using local
      anesthesia was associated with a lower incidence of difficult voiding and new
      onset urge symptoms.

PMID- 11956448
TI  - Martius flap harvest site: patient self-perception.
AB  - PURPOSE: We elucidated patient perception of the external genitalia after Martius
      flap harvesting. MATERIALS AND METHODS: We identified 8 women in whom a Martius
      interposition flap was used in association with transvaginal urethrolysis.
      Patients were contacted by an independent nurse and asked to evaluate the
      cosmetic appearance of the labium majus harvest site. They were also queried on
      any associated pain, numbness or altered sensation, or perceived interference
      with vaginal sexual relations. RESULTS: Of the 8 patients 2 (25%) believed that
      the harvest site appeared to be identical to its preoperative appearance, 2 (25%)
      believed that there were only minimal changes from the preoperative appearance, 1
      (12%) believed that it appeared markedly different from the contralateral side
      and 3 (38%) stated that they had never performed self-examination. Of the 8
      patients 1 (13%) complained of dyspareunia, 3 (38%) had intermittent discomfort
      in the harvest area 1 year after the operation and 5 (62%) perceived permanently
      decreased sensation or numbness at the harvest site. CONCLUSIONS: The Martius
      flap is not associated with a significant amount of perceived cosmetic
      disfigurement. It has relatively little effect on sexual relations.
      Postoperatively discomfort is minimal but there may be associated numbness or
      decreased sensation at the harvest site.

PMID- 11956449
TI  - Chemo-ablation of the prostate with dehydrated alcohol for the treatment of
      prostatic obstruction.
AB  - PURPOSE: We confirmed clinically whether chemo-ablation of the prostate with
      absolute ethanol may be an innovative transurethral approach for the relief of
      obstructive benign prostatic hyperplasia. METHODS: Using the InjecTx endoscopic
      device (Injectx Inc., San Jose, California) an initial cohort of 15 patients,
      including 13 who have now been followed more than 1 year, underwent elective
      transurethral chemo-ablation of the prostate. RESULTS: Preoperative and
      postoperative comparisons of the American Urological Association symptom score,
      maximum urine flow rate and prostatic volume reveal significant improvement with
      minimal discomfort and no major complication. CONCLUSIONS: The InjecTx technique
      proved encouragingly successful in this initial small-scale clinical trial.

PMID- 11956450
TI  - The long-term effect of specific type II 5alpha-reductase inhibition with
      finasteride on bone mineral density in men: results of a 4-year placebo
      controlled trial.
AB  - PURPOSE: We determine the effect of long-term suppression of dihydrotestosterone
      with finasteride, a specific type II 5alpha-reductase inhibitor, on bone mineral
      density. MATERIALS AND METHODS: As part of a large (3,040 cases) 4-year, double
      blind, placebo controlled trial designed to assess the long-term effects of
      finasteride in men with benign prostatic hyperplasia, 157 men 46 to 76 years old
      who were randomized to receive either 5 mg. finasteride or placebo underwent dual
      energy x-ray absorptiometry of the lumbar spine at baseline and at years 2, 3 and
      4. RESULTS: Of 117 patients who had a baseline measurement and at least 1
      additional measurement during the study baseline mean plus or minus standard
      deviation bone mineral density values were 1.12 +/- 0.17 gm./cm.2 in the
      finasteride group (63) and 1.10 +/- 0.17 gm./cm.2 in the placebo group (54).
      After 4 years bone mineral density was not different between treatment groups
      (finasteride 1.14 +/- 0.17 gm./cm.2 and placebo 1.13 +/- 0.18 gm./cm.2). Similar
      results were obtained for the 33 finasteride and 25 placebo treated patients who
      completed the study with year 4 bone mineral density measurements. CONCLUSIONS:
      These data demonstrate that long-term inhibition of type II 5alpha-reductase with
      finasteride does not adversely affect bone mineral density.

PMID- 11956451
TI  - Adult testicular torsion.
AB  - PURPOSE: Testicular torsion in adulthood is thought to be relatively unusual. We
      compared a series of men 21 years old or older with testicular torsion with a
      concurrent series of younger patients with torsion. MATERIALS AND METHODS: We
      reviewed the medical records of patients admitted with testicular torsion in a 9
      year period to hospitals affiliated with our institution. Data included patient
      demographics, history, physical findings, radiographic results if any, operative
      findings and outcome (testicular salvage versus loss). RESULTS: The charts of 48
      patients were evaluated. Excluded from study was a neonate with torsion and 3
      males who underwent delayed surgery for presumed missed torsion. Of the remaining
      44 patients we compared 17 who were 21 years old or older (range 21 to 34) with
      27 younger than 21 (range 8 to 20). The salvage rate differed in the 2 age groups
      with 70.3% of testes salvaged in the younger group versus only 41% in the older
      group. A factor affecting salvage in each group was time to presentation. In the
      older age group patients in whom the testis was lost had a significantly higher
      mean delay in presentation than those in whom it was salvaged (102 versus 11
      hours). A similar pattern was noted in the younger group with a mean time to
      presentation of 108 and 6.5 hours in those with testicular loss and salvage,
      respectively. Mean time between presentation and operation was 7.1 hours in the
      older and 4.8 in the younger group, which was not statistically different. A
      significant difference was noted in the degree of spermatic cord twisting. The
      cord was twisted a mean of 585 degrees in the adults versus 431 in the younger
      group. CONCLUSIONS: Testicular torsion in adults was more common in our series
      than expected. Salvage of the affected testis was better in younger patients,
      presumably due to less twisting of the cord.

PMID- 11956452
TI  - Effects of circumcision on male sexual function: debunking a myth?
AB  - PURPOSE: Claims of superior sexual sensitivity and satisfaction for uncircumcised
      males have never been substantiated in a prospective fashion in the medical
      literature. We performed such a study to investigate these assertions. MATERIALS
      AND METHODS: The Brief Male Sexual Function Inventory (BMSFI) was administered to
      sexually active males older than 18 years before undergoing circumcision. After a
      minimum interval of 12 weeks after the operation, the survey was again
      administered. The 5 domains of the BMSFI (sexual drive, erections, ejaculation,
      problem assessment overall satisfaction) were each given a summed composite
      score. These scores before and after circumcision were then analyzed by Wilcoxon
      signed-rank testing. RESULTS: All 15 men who participated in the study between
      September 1999 and October 2000 were available for followup. Mean patient age
      plus or minus standard deviation was 36.9 +/- 12.0 years. There was no
      statistically significant difference in the BMFSI composite scores of reported
      sexual drive (p >0.68), erection (p >0.96), ejaculation (p >0.48), problem
      assessment (p >0.53) or overall satisfaction (p >0.72). CONCLUSIONS: Circumcision
      does not appear to have adverse, clinically important effects on male sexual
      function in sexually active adults who undergo the procedure.

PMID- 11956453
TI  - Adult circumcision outcomes study: effect on erectile function, penile
      sensitivity, sexual activity and satisfaction.
AB  - PURPOSE: Evidence concerning the effect of circumcision on sexual function is
      lacking. Men circumcised as adults are potentially in a unique position to
      comment on the effect of a prepuce on sexual intercourse. We examine sexual
      function outcomes in men who have experienced sexual intercourse in the
      uncircumcised and circumcised states. MATERIALS AND METHODS: Men 18 years old or
      older when circumcised were identified by billing records during a 5-year period
      at an academic medical center. Medical charts were reviewed for confirmation of
      the procedure and to identify the indication(s). These men were surveyed to
      assess erectile function, penile sensitivity, sexual activity and overall
      satisfaction. Data were analyzed using paired t tests to compare category scores
      before and after circumcision. RESULTS: A total of 123 men were circumcised as
      adults. Indications for circumcision included phimosis in 64% of cases, balanitis
      in 17%, condyloma in 10%, redundant foreskin in 9% and elective in 7%. The
      response rate was 44% among potential responders. Mean age of responders was 42
      years at circumcision and 46 years at survey. Adult circumcision appears to
      result in worsened erectile function (p = 0.01), decreased penile sensitivity (p
      = 0.08), no change in sexual activity (p = 0.22) and improved satisfaction (p =
      0.04). Of the men 50% reported benefits and 38% reported harm. Overall, 62% of
      men were satisfied with having been circumcised. CONCLUSIONS: Our findings may
      help urologists better counsel men undergoing circumcision as adults. Prospective
      studies are needed to better understand the relationship between circumcision and
      sexual function.

PMID- 11956454
TI  - Patient preferences for outcomes associated with surgical management of prostate
      cancer.
AB  - PURPOSE: We used utility assessment to evaluate patient preferences for current
      urinary and sexual function after radical prostatectomy. MATERIALS AND METHODS:
      We measured preferences in 209 community volunteers enrolled in a prostate cancer
      screening study who underwent radical prostatectomy between 1994 and 1998. We
      compared preferences in 3 outcome groups, namely men bothered by current urinary
      and sexual functioning, only bothered by current sexual functioning and not
      bothered by current sexual or urinary functioning. Preferences were assessed via
      a computer based interview using time trade-off and standard gamble methods.
      Current functioning was assessed via a standardized questionnaire. RESULTS:
      Median time trade-off and standard gamble utilities were high at 0.9 across
      outcome groups, indicating that men were not willing to give up many remaining
      life years (10% of remaining life expectancy) with current functioning to achieve
      ideal functioning. However, mean time trade-off and standard gamble scores
      significantly decreased as the burden increased in men bothered by current sexual
      and urinary function (0.77 and 0.82), bothered by current sexual function only
      (0.87 and 0.89) and not bothered by sexual or urinary function (0.92 and 0.96,
      respectively). CONCLUSIONS: Health related quality of life was generally good in
      this observational study of patients treated for prostate cancer with radical
      prostatectomy. In addition, those bothered by urinary and/or sexual function
      would not be willing to trade much of the remaining life span to achieve perfect
      functioning. However, the perception of side effects was bothersome enough in
      some men to warrant appropriate patient counseling regarding the potential risks
      and benefits.

PMID- 11956455
TI  - A novel technique of exposure during radical retropubic prostatectomy.
AB  - PURPOSE: We describe a novel technique of enhanced exposure during radical
      retropubic prostatectomy in cases with significant cartilage overgrowth at the
      junction of the symphysis pubis. MATERIALS AND METHODS: At our institution 74
      radical retropubic prostatectomies were performed between July 1, 1998 and June
      30, 1999. In 9 cases (12%) exposure was limited by overgrowth of cartilage at the
      posterior aspect of the pubic symphysis. Electrovaporization of this
      cartilaginous outgrowth was performed using an extended Bovie tip on cut settings
      of approximately 250 W. using the Bard System 5000, Birtcher 5000 and 6400 series
      (Valley Lab, Boulder, Colorado). The cartilage was vaporized until flush with the
      pubic bone. RESULTS: This technique provided optimal exposure for direct
      visualization during the most critical part of the procedure. Added operative
      time was only 1 to 3 minutes. No intraoperative or postoperative complications
      were associated with this technique. CONCLUSIONS: We recommend this technique of
      vaporization when surgical exposure is limited by overhanging pubic symphysis
      cartilage. This technique enables better visualization during apical dissection,
      control of the dorsal vein complex and division of the urethra without additional
      operative time or surgical complications.

PMID- 11956457
TI  - Lymphoepithelioma-like carcinoma of the kidney.

PMID- 11956456
TI  - Simultaneous laparoscopic management of 3 urological malignancies.

PMID- 11956458
TI  - Lupus type anticoagulant in a patient with renal cell carcinoma: an autoimmune
      paraneoplastic syndrome.

PMID- 11956459
TI  - Bladder tumor producing granulocyte colony-stimulating factor and parathyroid
      hormone related protein.

PMID- 11956460
TI  - Aortoenteric fistula in advanced germ cell tumor: a rare lethal complication.

PMID- 11956461
TI  - Successful treatment of arterial priapism with alpha-agonist irrigation: a rural
      experience.

PMID- 11956462
TI  - Penile reconstruction with prosthesis and free skin graft in a patient with land
      mine blast injury.

PMID- 11956463
TI  - Training postgraduate urologists in laparoscopic surgery: the current challenge.
AB  - PURPOSE: We established a new mini-fellowship training model for teaching
      laparoscopic urological surgery to practicing urologists that provides a learning
      experience beyond that of a pelvic trainer or hands-on, animal laboratory based
      laparoscopic course. It provides the practitioner with clinical experience under
      mentor direct guidance and supervision before embarking on independent
      laparoscopic surgery at an individual hospital. MATERIALS AND METHODS: A mini
      fellowship model was developed that consists of 3 phases, namely 1) completing a
      2 to 3-day hands-on course in laparoscopy, including pelvic trainers and an
      animal model, 2) observing a clinical mentor perform 6 or more major renal
      laparoscopic cases and 3) performing 6 or more major renal procedures under
      mentor direct guidance in trainee patients at the mentor or trainee hospital
      after obtaining appropriate temporary privileges. RESULTS: Two community
      urologists underwent the mini-fellowship program in 2000. Trainee 1 performed 30
      laparoscopic procedures, including 17 radical nephrectomies, 4 simple
      nephrectomies, 4 nephroureterectomies, 4 renal cyst ablations and 1 renal biopsy,
      within the first 8 months after training and hospital accreditation. Trainee 2
      performed 10 laparoscopic procedures within the first 3 months after training and
      hospital accreditation. CONCLUSIONS: This mini-fellowship model provides
      practicing urologists with a clinically applicable teaching experience to learn a
      new surgical concept using a familiar training pattern. It may be a more rapid
      and safe process of disseminating laparoscopic urological surgery to community
      urologists. Based on this model it would be possible for centers of excellence in
      each state to establish similar training programs for the corresponding
      urological community, thereby, bringing the teaching of new surgical skills to a
      more clinically relevant level.

PMID- 11956464
TI  - Best practice policies for male infertility.

PMID- 11956465
TI  - Re: Evaluation of urinary continence and voiding function: early results in men
      with neo-uretheral modification of the Hautmann orthotopic neobladder.

PMID- 11956466
TI  - Re: Transrectal ultrasound guided biopsy of the prostate. Do enemas decrease
      clinically significant complications?

PMID- 11956467
TI  - The island flap technique for hypospadias repair. 1981.

PMID- 11956468
TI  - MAGPI (meatoplasty and lanuloplasty) a procedure for subcoronal hypospadias.
      1981.

PMID- 11956470
TI  - Ultrasound grade of hydronephrosis and severity of renal cortical damage on 99m
      technetium dimercaptosuccinic acid renal scan in infants with unilateral
      hydronephrosis during followup and after pyeloplasty.
AB  - PURPOSE: We performed ultrasonography and (99m)technetium dimercaptosuccinic acid
      (DMSA) renal scan in infants with unilateral hydronephrosis during followup and
      after pyeloplasty to examine the correlation of ultrasound hydronephrosis grade
      with the severity of renal cortical damage and assess the recovery of renal
      function in the obstructed kidneys after surgery. MATERIALS AND METHODS: We
      studied 80 boys and 19 girls with unilateral hydronephrosis detected in the first
      year of life, including 75 (76%) in whom it was detected prenatally. Ultrasound
      images were graded according to the Society for Fetal Urology grading system. The
      severity of renal cortical damage was assessed by DMSA renal scan. Absolute
      function of the right and left kidneys was estimated by DMSA uptake and relative
      DMSA uptake was calculated by the formula, relative uptake = uptake in obstructed
      kidney/total uptake in right and left kidneys x 100%. RESULTS: On ultrasonography
      grades 1 to 4 hydronephrosis were diagnosed in 9, 21, 19 and 50 kidneys,
      respectively. On DMSA renal scan cortical damage was detected in 10 kidneys (53%)
      with grade 3 and 49 (98%) with grade 4 hydronephrosis but not in kidneys with
      grade 1 or 2 disease. Dysfunction in the obstructed kidney, defined as relative
      DMSA uptake less than 40%, was noted in 13 patients with grade 4 hydronephrosis.
      Relative DMSA uptake significantly increased after successful pyeloplasty
      compared with preoperative uptake (44% +/- 2% versus 40.1% +/- 2%, p <0.01).
      CONCLUSIONS: Ultrasound grading of hydronephrosis correlates with the severity of
      cortical damage or the decrease in renal function on DMSA renal scan.
      Differential renal function on DMSA renal scan may be a useful and less invasive
      tool for determining surgical indications and examining changes in renal function
      after surgery.

PMID- 11956471
TI  - Extracorporeal shock wave lithotripsy in children.
AB  - PURPOSE: We analyzed the efficacy of extracorporeal shock wave lithotripsy in
      children. MATERIALS AND METHODS: Between 1987 and 2000, 15,423 patients with
      urinary calculi were treated at our institution, of whom 86 (0.56%) children 3 to
      14 years old underwent lithotripsy using the Siemens Lithostar Plus (Siemens
      Medical Systems, Iselin, New Jersey). A total of 121 calculi in 90 urinary tracts
      were treated requiring 149 extracorporeal shock wave lithotripsy sessions. The
      stones were caliceal in 62 cases, renal pelvic in 35, ureteral in 18 and staghorn
      in 6. Followup consisted of nephrotomogram or ultrasound 1 day and 1 to 3 months
      postoperatively. RESULTS: Complete removal of all stone fragments was achieved in
      97.6% of the stones after 3 months. Re-treatment was necessary in 24 patients
      (27.9%). All patients were treated as outpatients with intravenous sedation in 54
      (62.8%), general anesthesia in 13 (15.1%) and no anesthesia in 19 (22.1%).
      Complications were present in 8 patients (10.7%) who had colic and received
      medical treatment followed by uneventful recovery. CONCLUSIONS: Extracorporeal
      shock wave lithotripsy using the Lithostar Plus has been demonstrated to be an
      effective noninvasive procedure to treat radiopaque and even radiolucent or
      slightly opaque urinary calculi in children.

PMID- 11956472
TI  - Embryonal rhabdomyosarcoma passed per urethra.

PMID- 11956473
TI  - A novel solution for the short neourethra in Mitchell epispadias repair.

PMID- 11956474
TI  - Testicular migration: remodeling of connective tissue and muscle cells in human
      gubernaculum testis.
AB  - PURPOSE: We present the main morphological modifications in the human
      gubernaculum during testicular migration in humans. MATERIALS AND METHODS: We
      obtained 12 gubernacula from fresh, macroscopically normal human fetuses at 15 to
      29 weeks of gestation. Collagen was evidenced using trichrome and Sirius red
      staining procedures, while Weigert's resorcinol-fuchsin and anti-human elastin
      antibody were used to reveal elastic system fibers. Smooth muscle cells were
      detected by anti-human smooth muscle alpha-actin antibody. RESULTS: When the
      testes were still located in the abdomen at 15 to 16 weeks of gestation, collagen
      fibers were sparse and embedded in a loose extracellular matrix. The amount of
      fibers then gradually increased with age and at 28 weeks of gestation the
      gubernaculum was mostly collagenous in composition. Elastic fibers had a similar
      growth pattern, although they were located mainly at the distal end of the
      gubernaculum. Fibroblasts largely predominated over other cell types and
      decreased in number with gestational age, whereas smooth muscle cells were
      restricted to the walls of blood vessels. Striated muscle cells were detected at
      the scrotal end of the gubernaculum, where they were disposed as isolated and
      scattered bundles running in various directions. Like fibroblasts, their number
      also decreased with age. CONCLUSIONS: During testicular migration gubernacular
      connective tissue undergoes extensive remodeling and ultimately becomes an
      essentially fibrous structure rich in collagen and elastic fibers. Such changes
      should decrease the size of the gubernaculum and, thus, contribute to other
      forces that cause the testes to move toward the scrotum. In fact, because of the
      lack of smooth muscle cells, and the amount and organization of striated muscle
      cells, active contraction of the gubernaculum is less likely to be an important
      factor in testicular descent.

PMID- 11956475
TI  - Regional differences in the extracellular matrix of the human spongy urethra as
      evidenced by the composition of glycosaminoglycans.
AB  - PURPOSE: Despite the concept that the spongy urethra is a unique entity clinical
      evidence suggests the existence of segmental structural differences. The spongy
      urethra has a vascular nature, its cells may express different phenotypes and the
      extracellular matrix that they synthesize should reflect these differences.
      Glycosaminoglycans are components of the extracellular matrix that have key roles
      in the normal physiology and pathology of several tissues. Although total
      collagen content of the urethra was determined, we also analyzed urethral
      glycosaminoglycans (GAGs). MATERIALS AND METHODS: Fresh, macroscopically normal
      cadaveric urethral samples were obtained from 15 men who died at a mean age of
      25.4 years. The urethra was divided into glanular, penile and bulbar segments,
      which were then analyzed separately. Total GAG concentration was assessed by
      hexuronic acid assay and expressed as microg. hexuronic acid per mg. dry tissue,
      while the proportions of sulfated GAGs were determined by agarose gel
      electrophoresis. Hyaluronan concentration was determined by ion exchange
      chromatography and total tissue collagen was estimated as hydroxyproline content.
      RESULTS: Total GAG concentration was heterogeneous along the spongy urethra (p
      <0.001). Mean values plus or minus standard deviation in the glanular, penile and
      bulbar segments were 2.53 +/- 0.42, 2.11 +/- 0.47 and 1.47 +/- 0.4 microg./mg.,
      respectively. The most predominant GAG was hyaluronan and its highest mean
      concentration of 50.1% +/- 3.7% was found in the glanular urethra. The most
      predominant sulfated GAG in the male urethra was dermatan sulfate, followed by
      chondroitin sulfate and heparan sulfate. Total collagen content and the GAG-to
      collagen ratio varied along the spongy urethra and were lowest in the bulbar
      segment. CONCLUSIONS: The extracellular matrix of the human spongy urethra shows
      regional differences, as evidenced by biochemical analysis of GAG and collagen.
      This heterogeneity implies functional adaptations in the various segments and may
      affect the physiology and segmental incidence of urethral diseases.

PMID- 11956476
TI  - Association of vitamin D receptor gene polymorphism with urolithiasis.
AB  - PURPOSE: Recent studies suggest that allelic variations of the vitamin D receptor
      (VDR) gene can influence calcium absorption and excretion. Therefore, we studied
      the association of VDR gene polymorphism with urolithiasis. SUBJECTS AND METHODS:
      We studied 83 patients with urinary stones and 83 controls. Patients were scored
      for certain clinical characteristics, including long axis diameter of the largest
      stone (1 point-less than 10 mm. and 2-10 mm. or greater), number of stones (1
      point-1 and 2-multiple) and history of calcium stone disease (1 point-absent and
      2-present). They were classified into 3 groups according to the total score,
      including low-3, intermediate-4 or 5 and high-6 points. The 2 VDR gene
      polymorphisms TaqI and ApaI were detected by polymerase chain reaction
      restriction fragment length polymorphism and their relationships with the urinary
      calcium level were examined. RESULTS: The incidence of TaqI Tt and tt genotypes
      was significantly higher in the high score group than in controls. The TaqI t
      allele was associated with a 5.2-fold increase in the risk of severe stone
      disease. The urinary calcium level in patients with the Tt and tt genotypes was
      also higher than in those with the TT genotype. The rate of the ApaI genotype was
      not different in the high score group and controls. CONCLUSIONS: The TaqI t
      allele of the VDR gene may be a risk factor for severe stone disease and
      recurrent stones.

PMID- 11956477
TI  - Decreased renal expression of the putative calcium oxalate inhibitor Tamm
      Horsfall protein in the ethylene glycol rat model of calcium oxalate
      urolithiasis.
AB  - PURPOSE: Tamm-Horsfall protein is believed to inhibit calcium oxalate
      crystallization, aggregation or adhesion to the renal epithelium. We determined
      whether ethylene glycol induced urolithiasis changes the expression of renal and
      urinary Tamm-Horsfall protein. For comparison the expression of another calcium
      oxalate inhibitor, osteopontin, was also analyzed. MATERIALS AND METHODS: Male
      rats were treated with 0.75% ethylene glycol plus an AIN-76 diet (Dyets,
      Bethlehem Pennsylvania) (ethylene glycol group) or standard rat chow and water
      (control group) for up to 8 weeks (6 per group for 8 weeks and 3 per group for 3
      days to 6 weeks). Kidneys and urine (8 weeks only) were harvested and analyzed by
      Northern and Western blot analysis, and immunohistochemistry. RESULTS: Tamm
      Horsfall protein message and protein (membrane bound form) were decreased, while
      those of osteopontin were increased in the kidneys of rats treated with ethylene
      glycol for 8 weeks. As judged by immunochemistry Tamm-Horsfall protein and
      osteopontin were consistently present in a few tubules in rats in the ethylene
      glycol and control groups, respectively. In urine expression of the free form of
      Tamm-Horsfall protein (approximately 75 kDa.) was decreased but detectable in
      ethylene glycol treated rats. Although readily detected in tissue, osteopontin
      was not detected in the urine of control or ethylene glycol treated rats. In the
      time course experiment Tamm-Horsfall protein did not decrease until 4 weeks, when
      calcium oxalate crystals were detectable in the kidneys of treated rats. In
      contrast, osteopontin was increased, although inconsistently, beginning at 3
      days. CONCLUSIONS: Unlike other calcium oxalate inhibitors, such as osteopontin,
      renal message and protein for Tamm-Horsfall protein was decreased in ethylene
      glycol treated rats. Tamm-Horsfall protein expression did not decrease until
      aggregates of crystals had been deposited in the kidneys, while osteopontin
      expression began to increase almost immediately. Comparisons of the data on
      kidneys and urine obtained by RNA or protein blot analysis and immunochemistry
      underscore the need to examine tissue and urine by multiple techniques to obtain
      the most accurate assessment of how protein expression is changed by a given
      treatment.

PMID- 11956478
TI  - Evaluation of the use of a biodegradable ureteral stent after retrograde
      endopyelotomy in a porcine model.
AB  - PURPOSE: We evaluated the use of a poly-L-lactide-co-glycolide (PLGA)
      bioabsorbable ureteral stent after Acucise balloon incision (Applied Medical
      Resources, Rancho Santa Magarita, California) endopyelotomy in a porcine model.
      MATERIALS AND METHODS: After unilateral Acucise endopyelotomy in 9 female Yucatan
      minipigs a self-reinforced PLGA stent was placed in 5 (group 1) and a 7Fr double
      pigtail Percuflex stent (Boston Scientific, Natick, Massachusetts) was placed in
      4 (group 2). Preoperatively, and 6 and 12 weeks postoperatively plain x-ray of
      the kidneys, ureters and bladder, cystography, side specific creatinine clearance
      and retrograde ureterography were done. The contralateral ureters served as
      untreated controls. The 7Fr stents were removed at 6 weeks. All animals were
      sacrificed at 12 weeks after bilateral flow studies. Histological specimens from
      4 sites along the urinary tract were graded on a healing score of 0-normal, to 3
      severe changes. RESULTS: Side specific creatinine clearance was similar to
      preoperative values at 6 and 12 weeks. At the 2 time points plain x-ray of the
      kidneys, ureters and bladder in group 1 showed retroperitoneal stent fragments in
      3 of the 5 animals, which was confirmed at autopsy. Retrograde ureterography in
      group 1 showed mild hydronephrosis in all 5 ureters and saccular diverticula in
      4, which was similar in 2 and 3 animals, respectively, in group 2. Cystography
      demonstrated grades 1 to 2 reflux in 2 animals at 6 weeks but none at 12 weeks in
      group 1 and no reflux at either time point in group 2. Flow rates and healing
      scores were statistically similar in the 2 groups but the latter trended toward
      less favorable healing of ureteral musculature with application of the absorbable
      stent. CONCLUSIONS: In this pilot study the use of self-reinforced PLGA
      biodegradable ureteral stents was feasible after Acucise endopyelotomy in a
      porcine model with radiographic and fluid flow results that were relatively
      similar to those of standard 7Fr stents but with less favorable biocompatibility.

PMID- 11956479
TI  - Introducing the clusterin gene into human renal cell carcinoma cells enhances
      their metastatic potential.
AB  - PURPOSE: We recently reported a protective role of clusterin expression against
      apoptosis induced by a wide variety of stimuli in several human cancer models. In
      the current study we tested the hypothesis that clusterin over expression confers
      a benefit for the metastasis of renal cell carcinoma through the inhibition of
      apoptosis induced by the various obstacles the cancer cells may confront after
      detachment from their primary origin. MATERIALS AND METHODS: We introduced
      clusterin complementary DNA into human renal cell carcinoma ACHN cells, which do
      not express detectable level of clusterin expression, and generated the clusterin
      over expressing cell line ACHN/CL and the control vector only transfected cell
      line ACHN/C. In vitro anti-cell death activity under anchorage independent
      conditions among ACHN sublines was examined by limiting dilution assay and cell
      survival assay in suspension. To investigate the in vivo effects of clusterin
      over expression on metastatic potentials each cell line was injected into the
      tail vein or renal subcapsule of nonobese diabetic, severe combined
      immunodeficient mice and the metastatic features in all abdominal and thoracic
      organs were evaluated. RESULTS: ACHN/CL showed significantly enhanced growth in
      limiting dilution cultures compared with ACHN/C. The analysis of cell survival in
      the floating assay also revealed that ACHN/CL had a powerful survival advantage
      in suspension compared with ACHN/C. Furthermore, ACHN/CL formed more than 5-fold
      as many metastatic nodules in the lung after intravenous injection than ACHN/C.
      Similarly more marked lung metastasis was observed after implanting ACHN/CL cells
      into the renal subcapsule than after implanting ACHN/C cells. In contrast, there
      were no significant differences among ACHN sublines in the growth rates in vitro
      and in vivo, cell motility or invasive ability. CONCLUSIONS: These findings
      suggest that, if clusterin is over expressed, it prolongs cell survival under
      unfavorable conditions in the metastatic process, resulting in the enhanced
      metastatic potential of renal cell carcinoma.

PMID- 11956480
TI  - Inhibition of natural, interleukin-2 stimulated and bacillus Calmette-Guerin
      enhanced cytotoxicity with anti-CD16 antibodies.
AB  - PURPOSE: We studied the cytolytic mechanism of nonstimulated, bacillus Calmette
      Guerin (BCG) stimulated and interleukin (IL)-2 (Chiron Corp., Amsterdam, The
      Netherlands) stimulated peripheral blood mononuclear cells. MATERIALS AND
      METHODS: We inhibited the cytotoxicity of nonstimulated, BCG stimulated and IL-2
      stimulated peripheral blood mononuclear cells against various target cells using
      3 monoclonal antibodies directed against the CD16 receptor of natural killer
      cells or alternatively monoclonal antibodies against the alpha and beta subunits
      of the IL-2 receptor complex (IL-2R). The main target cell was the poorly
      differentiated transitional cell line T24. RESULTS: Of the 3 anti-CD16 antibodies
      tested only CLB FcR-gran/1 effectively inhibited natural, IL-2 stimulated and BCG
      enhanced cytotoxicity. Cytotoxicity was also markedly diminished after depletion
      of CD16+CD56+/- cells with CLB FcR-gran/1. An hour of pretreatment with CLB FcR
      gran/1 was enough to reduce significantly the level of cytotoxicity evoked by
      overnight stimulation with BCG or IL-2. Simultaneous administration of anti-IL
      2Ralpha and anti-IL-2Rbeta significantly decreased the killing of target cells by
      BCG stimulated and IL-2 stimulated peripheral blood mononuclear cells.
      CONCLUSIONS: Within the stimulation times chosen the same killing mechanisms
      seemed to explain the nonstimulated, BCG stimulated and IL-2 stimulated
      cytotoxicity with CD16 positive cells as central effectors. Anti-CD16 antibodies
      may deliver a target cell independent down-regulatory signal to natural killer
      cells or alternatively mimic a nonIg ligand and block the detection of the target
      cell.

PMID- 11956481
TI  - Pan-cadherin as a high level phenotypic biomarker for prostate cancer.
AB  - PURPOSE: High level phenotypic biomarkers such as cadherins are needed to
      identify individuals at risk for biologically active prostate cancer and
      determine which individuals with elevated prostate specific antigen or a prostate
      nodule are candidates for re-biopsy. Cadherins are a high level phenotypic
      biomarker associated with decreased cell adhesion, which is a cardinal event in
      carcinogenesis. Recently we reported that G-actin and tissue transglutaminase
      type II are potential biomarkers for prostate cancer. In this study we present
      cadherins as a potential third component of the biomarker profile. MATERIALS AND
      METHODS: Prostate tissues from 38 patients with cancer and 33 controls with a 10
      year prostate cancer-free followup were labeled for pan-cadherin by
      immunohistochemical testing. Immunoreactivity was quantified using a Pathology
      Workstation (Autocyte Inc., Elon College, North Carolina). RESULTS: Visually
      benign glands from controls generally expressed cadherins, whereas regions of
      adenocarcinoma were generally negative. On quantitative immunohistochemistry 36
      of 38 prostate cancer cases expressed a lower mean percent area positive for
      cadherin than the 19 benign prostatic hyperplasia and 14 prostatitis cases (odds
      ratio 978, 95% confidence interval 45 to 21,140, relative risk 18, 95% confidence
      interval 5 to 67, p <0.0001). Receiver operating characteristics analysis of
      immunohistochemical testing data showed that an optimal threshold of 7 produced
      95% sensitivity and 100% specificity. CONCLUSIONS: Quantitative down-regulation
      of cadherin expression in prostate cancer tissue sections is a strong biomarker
      for prostate cancer. Analysis of cadherin and other high level phenotypic
      biomarker expression in the premalignant field may provide additional diagnostic
      information to decide which patients need re-biopsy, more intensive monitoring or
      chemoprevention.

PMID- 11956482
TI  - Cross-linked matrix tissue sealant protects against mortality and hemorrhage in
      an acute renal injury model in heparinized rats.
AB  - PURPOSE: We evaluated the efficacy of a cross-linked matrix tissue sealant
      compared with oxidized cellulose and electrocautery in an acute renal injury
      model. MATERIALS AND METHODS: Sprague-Dawley rats underwent partial nephrectomy
      after intravenous heparin anticoagulation. The cut surface received 1 of 4
      therapies, namely no treatment, cross-linked matrix tissue sealant,
      electrocautery or Surgicel (Johnson & Johnson, New Brunswick, New Jersey)
      oxidized cellulose. Blood pressure was continually monitored, survival time was
      determined and total blood loss was quantified in each animal. RESULTS: Animals
      that received no treatment, electrocautery or oxidized cellulose died within 13
      minutes of injury with a decline in blood pressure to 0 mm. Hg. In cross-linked
      matrix treated rats hemostasis was immediate, resulting in no blood loss after
      cross-linked matrix application. Mean arterial pressure +/- SEM was maintained at
      136 +/- 6 mm. Hg. All cross-linked matrix treated animals survived. CONCLUSIONS:
      Cross-linked matrix tissue sealant provided immediate hemostasis and protection
      from a decline in blood pressure after renal trauma in heparinized rats. Cross
      linked matrix tissue sealant may benefit patients with severe renal injuries. In
      the future cross-linked matrix may be useful for long-term partial nephrectomy
      repair.

PMID- 11956483
TI  - Treatment of urethral defects: skin, buccal or bladder mucosa, tube or patch? An
      experimental study in dogs.
AB  - PURPOSE: We studied 3 graft materials and 2 urethroplasty techniques in 24 adult
      male mongrel dogs. MATERIALS AND METHODS: The animals were divided into 2 equal
      groups. In group 1 a 4 cm. segment of perineal urethra was excised and tubed
      urethroplasty was performed using free full-thickness skin, buccal and bladder
      mucosa grafts in 4 dogs each. In group 2 a 4 cm. urethral strip was excised and
      onlay urethroplasty was performed using the same graft materials in 4 dogs each.
      Retrograde urethrography was done and the animals were sacrificed at week 12.
      Autopsy specimens were calibrated with a 10Fr catheter. Hematoxylin and eosin
      stained sections were examined. Masson's trichrome stain was used to determine
      the extent of fibrosis. RESULTS: Urethral stricture was diagnosed by radiology
      and confirmed by calibration in 8 of the 12 dogs (66%) in group 1 but in only 1
      of the 12 (8%) in group 2 (p <0.004). Buccal mucosa grafts were associated with
      the lowest stricture rate of 12%, followed by 37% for bladder mucosa and 62% for
      skin (p <0.2). There was no difference in neovascularization among the 3 grafts.
      Graft shrinkage was less than 10% for buccal mucosa compared with 20% to 40% for
      skin and bladder mucosa. The shrinkage rate was similar for the onlay and tube
      techniques. The intensity of chronic inflammation and fibrosis was highest in the
      skin grafts. Circumferential fibrosis was noted in association with tubed
      urethroplasty but not with the onlay technique. CONCLUSIONS: The theoretical
      advantages of buccal mucosal grafts were pathologically demonstrated. When
      possible, grafts should be used as an onlay rather than as a complete tube.

PMID- 11956484
TI  - Tumor necrosis factor-alpha and interleukin-1beta mediate the production of
      nitric oxide involved in the pathogenesis of ifosfamide induced hemorrhagic
      cystitis in mice.
AB  - PURPOSE: We investigated the participation of nitric oxide in ifosfamide induced
      hemorrhagic cystitis in mice, and the involvement of tumor necrosis factor (TNF)
      alpha and interleukin (IL)-1beta in the induction of nitric oxide production in
      this model. MATERIALS AND METHODS: Hemorrhagic cystitis was induced in mice by
      100 to 400 mg./kg. ifosfamide and evaluated 6, 12, 24 or 48 hours thereafter by
      certain parameters, including vesical edema measurements, microscopic analysis
      and immunohistochemical testing for inducible nitric oxide synthase. Ifosfamide
      injected mice were pretreated with 10 to 40 mg./kg. of the nitric oxide synthesis
      inhibitor L-NG-nitroarginine methyl ester, 80 mg./kg. of mesna, a chemical
      antagonist of acrolein and the urotoxic metabolite of ifosfamide, 50 microl.
      antiserum against TNF-alpha and IL-1beta per mouse, 45 mg./kg. of the selective
      TNF-alpha synthesis inhibitor thalidomide or 200 mg./kg. of the TNF-alpha and IL
      1beta synthesis inhibitor pentoxifylline. RESULTS: Ifosfamide induced vesical
      edema, which peaked 12 hours after ifosfamide injection. Microscopic analysis
      revealed vascular congestion, edema, hemorrhage, fibrin deposition, neutrophil
      infiltration and epithelial denudation. Inducible nitric oxide synthase
      immunolocalization demonstrated intense reactivity to inducible nitric oxide
      synthase in the cytoplasm of bladder epithelial cells, which showed diffuse
      necrosis. Pretreatment with mesna reduced the increases in vesical edema, while
      treatment with L-NG-nitroarginine methyl ester, antiserum to TNF-alpha or IL
      1beta, thalidomide or pentoxifylline inhibited vesical edema and microscopic
      alterations. Antiserum treatments also inhibited the expression of inducible
      nitric oxide synthase in the urothelium. CONCLUSIONS: Nitric oxide produced by
      inducible nitric oxide synthase is involved in urothelial damage and in the
      inflammatory events leading to hemorrhagic cystitis after ifosfamide
      administration in mice. The induction of inducible nitric oxide synthase in the
      urothelium appears to depend on the synergistic effect of IL-1beta and TNF-alpha.

PMID- 11956486
TI  - Effects of tiagabine, a gamma-aminobutyric acid re-uptake inhibitor, on normal
      rat bladder function.
AB  - PURPOSE: Previous reports have demonstrated the inhibitory effect of exogenous
      gamma-aminobutyric acid (GABA) on micturition. In the current study we tested
      whether tiagabine (Sanofi Synthelab., Newcastle-upon Tyne, United Kingdom), a
      GABA re-uptake inhibitor increasing endogenous GABA concentrations, would affect
      micturition in awake rats or influence rat detrusor contraction in vitro.
      MATERIALS AND METHODS: Nonanesthetized female Sprague-Dawley rats underwent
      cystometric investigation in a metabolic cage. Micturition was stimulated by
      infusing saline intravesically. Micturition parameters were recorded and compared
      before and after drug administration. In vitro the effects of tiagabine on
      electrical and carbachol induced contractions in bladder strips were
      investigated. Furthermore, it was studied whether tiagabine interfered with
      electrically induced release of acetylcholine. RESULTS: Intravenous
      administration of 5 and 20 mg. kg.-1 tiagabine in 7 and 9 rats decreased
      micturition pressure a mean plus or minus standard error of mean of 21% +/- 11%
      and 42% +/- 9%, and decreased voided volume a mean of 31% +/- 9% and 33% +/- 9%,
      respectively. At 20 mg. kg.-1 tiagabine intravenously increased post-void
      residual volume a mean of 300% +/- 120% and decreased bladder capacity a mean of
      14% +/- 3%. Tiagabine (100 microg.) intrathecally in 7 rats reduced micturition
      pressure a mean of 34% +/- 10% and increased bladder capacity a mean of 30% +/-
      9% and post-void residual volume a mean of 250% +/- 75%. However, voided volume
      was not changed. In vitro studies demonstrated that tiagabine attenuated bladder
      contractions induced by electrical field stimulation to a mean of 69% +/- 6% of
      controls at 100 microM. but did not affect contractions induced by carbachol.
      Release studies revealed that tiagabine inhibited electrical induced
      acetylcholine release to a mean of 82% +/- 5% of controls at 100 microM.
      CONCLUSIONS: The current results show that tiagabine has an inhibitory action on
      rat micturition. The site of action may be central and peripheral.

PMID- 11956485
TI  - Localization and role of nitric oxide synthase and endogenous nitric oxide
      synthase inhibitors in the rabbit lower urinary tract.
AB  - PURPOSE: We investigated the possible role of endogenous methylarginine
      derivatives, such as NG-monomethyl-L-arginine (L-NMMA), asymmetrical NG, NG
      dimethyl-L-arginine (ADMA) and symmetrical NG, N'G-dimethyl-L-arginine (SDMA),
      for regulating nitric oxide synthase in the rabbit lower urinary tract. MATERIALS
      AND METHODS: Strips of detrusor, trigone and proximal urethra were processed for
      the determination of endogenous methylarginines and L-arginine by automated high
      performance liquid chromatography. We also compared nitric oxide synthase
      activity and nitric oxide mediated functional responses to electrical field
      stimulation in the 3 regions. Nitric oxide synthase activity was measured by
      determining the conversion of [3H] L-arginine to [3H] L-citrulline. RESULTS: L
      NMMA, ADMA and SDMA were detectable by high performance liquid chromatography in
      the detrusor, trigone and proximal urethra. Electrical field stimulation induced
      nitric oxide mediated prominent relaxation in the trigone and proximal urethra,
      while no relaxation response was observed in the detrusor. Exogenously applied 1
      to 100 microM. L-NMMA and 1 to 100 microM. ADMA but not 100 microM. SDMA
      dependently inhibited Ca2+ dependent nitric oxide synthase activity in all
      regions, and electrical field stimulation induced relaxation in the trigone and
      proximal urethra. Inhibition with L-NMMA and ADMA was blocked in the presence of
      3 mM. L-arginine but not by 3 mM. D-arginine. CONCLUSIONS: Three methylarginines
      and nitric oxide synthase are localized throughout the rabbit lower urinary
      tract. Endogenous L-NMMA and ADMA may be involved in regulating nitric oxide
      biosynthesis of the micturition reflex in the normal or disease state.

PMID- 11956487
TI  - Passive biaxial mechanical properties of the rat bladder wall after spinal cord
      injury.
AB  - PURPOSE: Changes in the mechanical properties of the bladder wall after spinal
      cord injury can alter bladder compliance and wall tension, leading to changes in
      afferent nerve activity and to abnormal reflex mechanisms. To our knowledge we
      report the first application of biaxial mechanical testing to the normal bladder
      wall and demonstrate how these properties change after spinal cord injury.
      MATERIALS AND METHODS: Whole bladders were harvested from mature female Sprague
      Dawley rats weighing 250 to 300 gm. Test group animals underwent complete spinal
      cord transection at the T9 to T10 level and normal animals comprised the control
      group. The bladders were cut open longitudinally, the trigone and apex were
      removed and the remaining tissue was trimmed to a square of 9 to 13 mm. per side.
      Mechanical properties of the tissue sample were tested using planar biaxial
      testing, in which a stress was applied in the circumferential and longitudinal
      (base-apex) directions, and resulting axial strains were measured. RESULTS: In
      normal and spinal cord injured rats bladder wall tissue demonstrated isotropic
      mechanical behavior when equal stress levels were applied in anatomical
      directions. However, under nonequi-biaxial loading bladder specimens were not
      truly isotropic but displayed anisotropic-like behavior. Spinal cord injured
      tissues were consistently more compliant than normal controls. CONCLUSIONS:
      Biaxial mechanical testing can detect differences in normal control and
      hypertrophied rat bladders 10 and 14 days after spinal cord injury. These changes
      represent an important component of the bladder response to spinal cord injury.

PMID- 11956488
TI  - Effect of oral Tadenan treatment on rabbit bladder structure and function after
      partial outlet obstruction.
AB  - PURPOSE: There is increasing evidence that the progressive dysfunction induced by
      partial outlet obstruction is mediated by ischemia-reperfusion, and bladder
      decompensation results from ischemia-reperfusion induced damage to the cellular
      and subcellular organelle membranes of nerve and smooth muscle, mitochondria and
      sarcoplasmic reticulum. Tadenan, an extract of Pygeum africanum, is a therapeutic
      prescribed in Europe to relieve symptoms of obstructive bladder dysfunction
      secondary to benign prostatic hyperplasia. There is excellent experimental
      evidence that Tadenan treatment of obstructed rabbits reduces and reverses the
      progression of bladder decompensation. We determined whether Tadenan therapy can
      reverse the morphological damage associated with obstructive dysfunction.
      MATERIAL AND METHODS: A total of 36 male New Zealand White rabbits were separated
      into 6 groups of 6 each. Rabbits in groups 1 and 2 underwent sham operation. For
      3 weeks beginning 2 weeks after sham operation group 1 was treated with vehicle
      and group 2 was treated with 30 mg./kg. Tadenan daily. Rabbits in groups 3 to 6
      underwent partial outlet obstruction surgery. Two weeks after obstruction each
      rabbit was treated for 3 weeks with vehicle in group 3, and with 1, 10 and 30
      mg./kg. Tadenan in groups 4, 5 and 6, respectively. After the completion of
      treatment cystometry was performed on each rabbit and isolated bladder strips
      were evaluated for contractile responses to field stimulation, adenosine
      triphosphate, carbachol and KCl. Separate strips were fixed for electron
      microscopy to determine the location and severity of cellular and subcellular
      membrane damage. RESULTS: Partial outlet obstruction resulted in reduced
      compliance, decreased responses of bladder strips to all forms of stimulation
      tested, and significant and extensive damage to cellular and subcellular
      organelle membranes consistent with an ischemia-reperfusion etiology. Daily 1 and
      10 mg./kg. Tadenan treatments had little effect on the obstruction induced
      increase in bladder weight or the deleterious changes in bladder function and
      structure. However, treating obstructed rabbits with 30 mg./kg. Tadenan daily
      resulted in reduced bladder hypertrophy, improved compliance, improved
      contractile responses to nearly normal levels of isolated bladder strips to all
      stimuli tested and reversal of obstruction induced structural damage to cellular
      and subcellular organelle membranes. CONCLUSION: Tadenan treatment of obstructed
      rabbits resulted in a dose dependent improvement in bladder ultrastructure in
      parallel with improved bladder compliance and contractile responses of isolated
      strips to stimulation, providing support for the hypothesis that damage to
      cellular and subcellular organelle membranes mediates the contractile dysfunction
      induced by partial outlet obstruction.

PMID- 11956489
TI  - Effect of oral Kohki tea on bladder dysfunction induced by severe partial outlet
      obstruction.
AB  - PURPOSE: Extracts of the leaves of Engelhardtia chrysolepis, a subtropical plant
      that grows wild in southern China, have been used medicinally in east Asia for
      hundreds of years. A standard extract named Kohki tea (Maruzen Pharmaceuticals,
      Onomichi City, Japan) is sold over the counter in Japan as a sweet tea shown to
      confer many beneficial effects on general health and well-being. The tea contains
      strong antioxidants, including several dihydroflavonol glycosides. The results of
      previous studies show that natural products with antioxidant activities provide
      protective effects on the bladder of rabbits with partial outlet obstruction. We
      determined in vivo and in vitro whether oral pretreatment of rabbits with Kohki
      tea protects the bladder from dysfunction induced by partial outlet obstruction.
      MATERIALS AND METHODS: A total of 28 New Zealand White rabbits were separated
      into 4 groups of 7 each. Rabbits in groups 1 and 2 were treated by gavage with
      100 mg./kg. Kohki tea daily in distilled water, while those in groups 3 and 4
      were given distilled water. After 4 weeks of daily oral administration each
      rabbit was sedated, the bladder was catheterized and cystometry was performed at
      a filling rate of 1 ml. per minute. At the completion of cystometry the rabbits
      were immediately anesthetized. Moderate outlet obstruction was created in groups
      1 and 3, and sham surgery was performed in groups 2 and 4. Treatment was
      continued for an additional 4 weeks, when each rabbit was sedated and cystometry
      was repeated. After cystometry the bladder was exposed through a midline
      incision, excised, weighed and 4 strips of bladder body were cut for
      contractility studies. The balance of the bladder was separated between smooth
      muscle and mucosa by blunt dissection, frozen in liquid nitrogen and stored at 
      70C for biochemical analyses. RESULTS: Partial outlet obstruction stimulated
      similar increases in the bladder weight of all obstructed rabbits. Partial outlet
      obstruction resulted in a significant decrease in bladder compliance in all
      obstructed animals. However, the bladder of obstructed rabbits given Kohki tea
      were significantly more compliant than those given water. Voiding pressures in
      the control group and the obstructed group given distilled water were
      approximately equal, while obstructed rabbits given Kohki tea showed
      significantly higher maximal voiding pressure. The contractile responses to all
      forms of stimulation were reduced by obstruction to a significantly greater
      degree in the rabbits not given tea than in those given tea. Sarcoplasmic
      reticulum Ca2+-adenosine triphosphatase enzyme activity of the bladder was
      significantly reduced in obstructed rabbits given vehicle but activity was not
      reduced in obstructed rabbits given Kohki tea. CONCLUSIONS: Kohki tea had a
      significant protective effect on bladder function, contractile responses and
      bladder biochemistry in rabbits with moderate to severe partial outlet
      obstruction.

PMID- 11956490
TI  - Distribution of chronic prostatitis in radical prostatectomy specimens with up
      regulation of bcl-2 in areas of inflammation.
AB  - PURPOSE: We examined the anatomical relationship of chronic prostatitis with
      prostate cancer and benign prostatic hyperplasia (BPH) based on the hypothesis
      that there may be an association of prostatitis with these other entities that
      may involve up-regulation of bcl-2. MATERIALS AND METHODS: We examined 40 whole
      mount radical prostatectomy specimens for the presence and distribution of
      chronic inflammatory infiltrate. Immunostaining for bcl-2 was done in 10 cases.
      RESULTS: Chronic prostatitis was identified in all 40 cases with peripheral zone
      inflammation in 95% and transition zone inflammation in 87.5%. In all cases of
      transition zone inflammation the infiltrate was noted within and/or around BPH.
      Inflammatory infiltrate was microscopically associated with prostate cancer in 23
      of the 40 cases (57.5%). In these 23 cases, there was no association of
      inflammation with Gleason score, preoperative prostate specific antigen, positive
      margins, or seminal vesicle invasion. Patients with BPH unassociated with
      prostatitis had significantly smaller prostate weight (median 32 gm.) and were
      younger (mean age 54.4 years) than those with BPH associated with prostatitis
      (median weight 40 gm. and mean age 61.4 years, p <0.05). Bcl-2 staining was
      intensified in benign glands within areas of prostatitis in all 10 cases
      examined. CONCLUSIONS: Chronic prostatitis is a common finding in radical
      prostatectomy specimens. Inflammation was associated with BPH and cancer but had
      a greater tendency to be associated with BPH. Bcl-2 was prominently expressed in
      areas of prostatitis. Our findings indirectly support a potential role for
      prostatitis in the pathogenesis of BPH.

PMID- 11956491
TI  - Immunolocalization of multidrug resistance protein 5 in the human genitourinary
      system.
AB  - PURPOSE: The intracellular messenger cyclic guanosine monophosphate (cGMP) has an
      important role in regulating smooth muscle tone. An increase in intracellular
      cGMP levels is a prerequisite for penile erection. Inhibition of cGMP degradation
      by cGMP specific phosphodiesterase 5 has been used for treating erectile
      dysfunction. In addition to degradation by phosphodiesterase, cGMP is exported
      from cells by multidrug resistance protein 5 (MRP5), also called ABCC5, which we
      recently identified as an adenosine triphosphate dependent export pump for cGMP.
      MRP5 is potently inhibited by substances known as phosphodiesterase inhibitors,
      including sildenafil and trequinsin. Therefore, we analyzed whether MRP5 is
      expressed in tissues of the human genitourinary system and whether MRP5 and
      phosphodiesterase 5 proteins are localized in the same cell types. MATERIALS AND
      METHODS: Localization of MRP5 and phosphodiesterase 5 was analyzed by
      immunofluorescence microscopy in cryosections of various tissues of the human
      genitourinary system. RESULTS: MRP5 and phosphodiesterase 5 were co-expressed in
      smooth muscle cells of the corpus cavernosum, ureter, urethra and bladder. In
      addition, MRP5 and phosphodiesterase 5 were localized in epithelial cells of the
      mucosa in the ureter and urethra, and in blood vessels of the lamina propria.
      CONCLUSIONS: The co-expression of MRP5 and phosphodiesterase 5 in smooth muscle
      cells of the genitourinary system indicates 2 distinct pathways for cGMP removal.
      Thus, MRP5 inhibition represents a new approach for enhancing cGMP levels in
      smooth muscle cells and developing drugs for erectile dysfunction.

PMID- 11956492
TI  - Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile
      responses in the rat.
AB  - PURPOSE: Activation of soluble guanylate cyclase with a subsequent increase in
      intracellular levels of cyclic guanosine monophosphate is necessary for normal
      erection. In vascular tissue 3(5'-hydroxymethyl-2'-furyl-1-benzyl indazole (YC-1)
      (Abbott Laboratories, North Chicago, Illinois) has been shown to stimulate
      soluble guanylate cyclase independent of nitric oxide. We studied whether YC-1
      modulates erectile responses in the rat. MATERIALS AND METHODS: The effects of YC
      1 given intracavernously or intraperitoneally on intracavernous pressure were
      investigated in rats. Functional effects of YC-1 on neuronal and endothelial
      nitric oxide relaxations were studied in 3 x 10(-6) M. 1-noradrenaline contracted
      preparations of rat isolated corpus cavernosum. RESULTS: Intracavernous YC-1 (10
      micromol. kg.-1) produced erectile responses with a mean intracavernous pressure
      plus or minus standard error of mean of 81 +/- 17 cm. water (p <0.001) and a mean
      duration of 7.1 +/- 3.3 minutes (p <0.001). YC-1 (10 micromol. kg.-1) given
      intraperitoneally also increased the amplitude and duration of erectile responses
      to cavernous nerve stimulation. Mean peak intracavernous pressure increased from
      63 +/- 6 to 10(2) +/- 16 cm. water (p <0.05). Erections induced by a submaximal
      dose of 25 microg. kg.-1 apomorphine s.c. increased in number after 10 micromol.
      kg.-1 YC-1 intraperitoneally (p <0.05). In vitro nerve induced relaxant responses
      were enhanced by increasing concentrations of YC-1. Relaxations at 20 Hz. were
      increased from a mean of 9% +/- 5% to 52% +/- 5% at a YC-1 concentration of 10(
      5) M. (p <0.001). At this concentration carbachol induced relaxations were
      enhanced from a mean of 19% +/- 3% to 40% +/- 9% (p <0.05). CONCLUSIONS: YC-1 can
      evoke erectile responses when given intracavernously and it enhances erections
      induced by cavernous nerve stimulation and apomorphine when given systemically.
      In vitro YC-1 enhances electrically evoked relaxations in rat corpus cavernosum.
      YC-1 represents an interesting pharmacological principle that may be useful for
      treating erectile dysfunction.

PMID- 11956493
TI  - Osteotesticular protein tyrosine phosphatase expression in rodent testis.
AB  - PURPOSE: In the last decade the novel receptor-like protein tyrosine phosphatase
      was identified and termed osteotesticular tyrosine phosphatase (OST-PTP) due to
      its restricted expression in bone and testis. OST-PTP expression is regulated
      during osteoblast differentiation and it shows stage specific expression in the
      testis. Confined OST-PTP expression in the basal compartment of the seminiferous
      tubules suggests that this protein may be a good candidate for a rodent germ stem
      cell marker. To test this hypothesis we determined the exact pattern of OST-PTP
      expression in the rodent testis. MATERIALS AND METHODS: Adult mouse and rat
      paraffinized testis sections were subjected to in situ hybridization using
      riboprobes against the receptor and catalytic domains of the protein OST-PTP.
      RESULTS: OST-PTP testicular expression in rodents is not confined to the
      spermatogonia, as previously suggested, but is also present in Sertoli cells in a
      stage independent pattern. This finding excludes the hypothesis that OST-PTP is a
      germ stem cell identification marker in rodents. In addition, we report the
      identification of a testicular OST-PTP isoform lacking part of a catalytic domain
      that is widely expressed during spermatogenesis in all cell types. CONCLUSIONS:
      This finding implies tight control over OST-PTP expression in the testis, which
      in turn suggests an important role for OST-PTP and its isoform in male germ cell
      differentiation.

PMID- 11956495
TI  - Chemoradiotherapy for muscle invading bladder carcinoma. Final report of a single
      institutional organ-sparing program.

PMID- 11956494
TI  - Comparison of intussusception pull-through end-to-side and conventional end-to
      side microsurgical vasoepididymostomy: prospective randomized controlled study in
      male wistar rats.
AB  - PURPOSE: Vasoepididymostomy is a technically challenging and complex
      microsurgical procedure. Recently a new triangulation end-to-side microsurgical
      technique was reported that allows intussusception of the epididymal tubule into
      the vasal lumen, resulting in a higher clinical patency rate of 92% with shorter
      operative time in preliminary clinical studies. We performed a prospective
      controlled randomized study comparing the patency rate, postoperative sperm
      granuloma rate and operating time of conventional and intussusception end-to-side
      vasoepididymostomy in previously vasectomized rats. MATERIALS AND METHODS: We
      randomized 42, 6-week-old male Wistar rats into 4 groups, including 6 into the
      sham operation, and 12 each into the control, conventional end-to-side and
      intussusception end-to-side vasoepididymostomy groups. Bilateral 2-clip vasectomy
      was performed in all animals except those in the sham operation group. Bilateral
      intussusception or conventional end-to-side vasoepididymostomy was performed in
      the assigned animals 2 weeks after vasectomy. Animals in the control group
      underwent vasectomy only. In the sham operation group the testes were mobilized
      out of the scrotum and then returned. Rats were sacrificed at 8, 12, 16 and 24
      weeks, respectively. The anastomosis and vasectomy sites were inspected for sperm
      granuloma. To assess patency the abdominal end of the vas was transected and
      intraluminal fluid was examined microscopically at 400x magnification for the
      presence of motile sperm. Patency was further confirmed by performing retrograde
      indigo carmine vasography through the anastomoses. RESULTS: In the
      intussusception and conventional groups the patency rate was 91.7% and 54.2% (p =
      0.004), the sperm granuloma rate was 20.8% and 58.4% (p = 0.035), and average
      operative time was 65.8 and 67.7 minutes (p = 0.197), respectively. CONCLUSIONS:
      Intussusception end-to-side vasoepididymostomy is superior to conventional end-to
      side vasoepididymostomy with respect to the patency and postoperative sperm
      granuloma rates. Further investigations are required to confirm such findings
      clinically in humans.

PMID- 11956496
TI  - The continuing challenge of opportunistic infections.

PMID- 11956497
TI  - Opportunistic infections: an update.
AB  - With highly active antiretroviral therapy (HAART), the overall incidence of
      opportunistic infections (OIs) has declined and survival after an AIDS-defining
      event has improved. However, rates of mycobacterial diseases and cytomegalovirus
      (CMV) disease remain high for the first 3 months before declining. Achieving a
      CD4 count of 200 cells/ micro l after 6 months of HAART is a valuable marker for
      a subsequent low risk of OIs. Different clinical manifestations of OIs may be
      attributable to immunopathogenic mechanisms linked to immune reconstitution on
      HAART. The recommendations on prophylaxis and maintenance therapy need to be
      redefined to allow for the decreased risk of OIs in HAART-treated patients. There
      are strong data in favour of discontinuing primary prophylaxis against
      Pneumocystis carinii pneumonia, toxoplasma encephalitis and Mycobacterium avium
      infection.

PMID- 11956499
TI  - Mycobacterial diseases and HIV.
AB  - This article focuses on tuberculosis (TB) and Mycobacterium avium complex (MAC),
      as these are the most important of the mycobacterioses in HIV-infected patients.
      It is estimated that in 1999, HIV-related TB reached 1000000 cases and caused 30%
      of the 2500000 AIDS-related deaths. In HIV-infected patients, TB may have unusual
      clinical features and can cause diagnostic difficulties. Despite the
      effectiveness of modern short-course treatment, mortality due to HIV-related TB
      remains high both during and after treatment. While highly effective therapy
      exists for both HIV and TB, concomitant administration is fraught with
      difficulties and many physicians delay HAART for 2 or more months to minimise the
      risk of toxic side effects. Patients with CD4 counts <50 cells/micro l should
      receive MAC prophylaxis. Clarithromycin or azithromycin are the preferred agents.

PMID- 11956498
TI  - Pneumocystis carinii: where are we now?
AB  - Pneumocystis carinii pneumonia (PCP) is still the commonest AIDS-defining
      condition in the UK, although absolute numbers have fallen since 1990 with the
      advent of prophylaxis and highly active antiretroviral therapy (HAART). Further
      decreases in its incidence are unlikely unless efforts are made to reduce late
      first presentations of HIV, improve retention of patients in care and improve
      adherence to P. carinii prophylaxis. The widespread development of key mutations
      in the P. carinii dihydropteroate synthase gene in the 1990's suggests that the
      organism is evolving under positive evolutionary pressure, possibly mediated by
      widespread use of co-trimoxazole and dapsone prophylaxis. It is not clear whether
      these mutants lead to treatment failure with co-trimoxazole, since most episodes
      are treated successfully and failure of prophylaxis is rare. Molecular diagnosis
      of PCP is restricted to research use, due to difficulties with sensitivity,
      specificity and turn-around times. Patients are infected with multiple P. carinii
      subtypes and re-infection from an environmental source is probably more important
      than re-activation of an existing infection. Person-to-person transmission does
      not appear to be a major source of infection in HIV-infected patients. Recent
      reports have highlighted the potential complications of initiating HAART during
      treatment of PCP.

PMID- 11956500
TI  - Opportunistic protozoan diarrhoea.
AB  - In the developed world, a significant increase in the incidence of protozoan
      diarrhoea was observed following the AIDS epidemic. The profound immunodeficiency
      associated with advanced HIV disease produced increased susceptibility to
      opportunistic protozoan infections. The resultant profuse diarrhoea,
      malabsorption and weight loss contributed to the high morbidity and mortality
      rates associated with the epidemic. The success of highly active antiretroviral
      therapy (HAART) in suppressing viral replication has led to a reduced incidence
      of AIDS-related opportunistic infections and this has contributed to decreased
      morbidity and mortality. In this review, we examine current management practices
      for HIV-related opportunistic protozoan diarrhoea

PMID- 11956501
TI  - Treatment of opportunistic infections and lymphoma in the nervous system.
AB  - The advent of highly active antiretroviral therapy has affected many aspects of
      the management of AIDS-related opportunistic infections (OIs). Aspects of
      treating OIs of the brain, spinal cord, peripheral nerves and muscles are
      discussed, with emphasis on more recent developments in this area. Treatment for
      primary and metastatic central nervous system lymphoma is also reviewed.

PMID- 11956502
TI  - Prioritization of medical problems to improve adherence.

PMID- 11956503
TI  - Acute hypoxia and cytochrome P450-mediated hepatic drug metabolism in humans.
AB  - OBJECTIVE: Our objective was to investigate the effect of acute hypoxia on the
      activity of hepatic cytochrome P450 (CYP) enzymes. METHODS: Twelve healthy
      subjects who lived at sea level were exposed to altitude-induced hypoxia for 7
      days at 4559 m above sea level. Hepatic CYP enzyme activity was measured before
      departure, at 24 and 96 hours after arrival to high-altitude location, and at 1
      month after return to sea level. CYP enzyme activities were measured by means of
      the metabolic ratios of sparteine (CYP2D6), endogenous cortisol metabolism
      (CYP3A4), and caffeine (CYP1A2), as well as by the S/R ratio of mephenytoin
      (CYP2C19) and antipyrine clearance. RESULTS: The metabolic ratio of sparteine
      increased after 24 hours at high altitude (median difference, 0.15; 95%
      confidence interval, 0.05 to 0.28) and remained increased after 96 hours. The
      ratio decreased after return to sea level (median difference, -0.15; 95%
      confidence interval, -0.29 to -0.03; P =.016, Friedman test). The metabolic ratio
      of cortisol decreased after 24 hours (median difference, -2.0; 95% confidence
      interval, -3.5 to -0.5) but returned to sea level values after 96 hours at high
      altitude (median difference, 1.6; 95% confidence interval, 1.0 to 4.2; P =.047,
      Friedman test). These changes indicate a small decrease in the activity of CYP2D6
      and CYP3A4. There were no significant changes regarding the metabolic ratio of
      caffeine, the S/R ratio of mephenytoin, or antipyrine clearance. CONCLUSION: The
      small changes observed suggest that acute hypoxia has no clinically significant
      effects on CYP enzymes in humans.

PMID- 11956504
TI  - The value of plasma acetaminophen half-life in antidote-treated acetaminophen
      overdosage.
AB  - BACKGROUND: A plasma acetaminophen (INN, paracetamol) half-life of more than 4
      hours has been correlated with hepatotoxicity in acetaminophen overdosing not
      treated with an antidote. Acetaminophen half-life has not been studied in
      patients receiving the antidote N -acetylcysteine. METHODS: Prospectively, 112
      patients with acetaminophen overdosage all treated with intravenous N 
      acetylcysteine were studied. A minimum of 2 plasma acetaminophen values >20
      micromol/L were available for calculation of acetaminophen half-life, assuming
      first-order kinetics. RESULTS: Overall, the median acetaminophen half-life was
      5.4 hours (range, 0.8-119.7 hours). Forty-eight patients with no or little
      hepatotoxicity (ALT <1000 U/L), 43 patients with hepatotoxicity without
      encephalopathy, and 21 patients with hepatotoxicity and encephalopathy had
      acetaminophen half-lives of 3.0 hours (range, 0.8-10.0 hours), 6.4 hours (range,
      1.3-19.0 hours), and 18.4 hours (range, 4.6-119.7 hours), respectively (P <.001).
      An acetaminophen half-life >4 hours was observed in 71 patients, and 56 of those
      (79%) had hepatotoxicity (ALT >1000 U/L or coma). Thirty-three of 41 patients
      (81%) with an acetaminophen half-life <4 hours had no hepatotoxicity. A receiver
      operating characteristic curve analysis showed that an acetaminophen half-life of
      5.5 hours provided better discrimination; hepatotoxicity was therefore present in
      49 of 54 patients with an acetaminophen half-life >5.5 hours (positive predictive
      value, 91%) and in 15 of 58 patients with a half-life below this limit (negative
      predictive value, 74%) despite treatment with N -acetylcysteine. CONCLUSIONS:
      Acetaminophen half-life correlates well with the degree of liver damage in
      patients treated with the antidote N-acetylcysteine. Longer half-lives reflect a
      greater toxic effect on the liver.

PMID- 11956505
TI  - Effect of voriconazole on the pharmacokinetics of cyclosporine in renal
      transplant patients.
AB  - OBJECTIVE: Voriconazole is a broad-spectrum triazole antifungal agent under
      investigation for opportunistic infections that often target immunosuppressed
      patients. This study investigated the effect of voriconazole on the
      pharmacokinetics of cyclosporine (INN, ciclosporin). METHODS: This was a
      randomized, double-blind, placebo-controlled, crossover study in kidney
      transplant recipients with stable renal function who were receiving cyclosporine
      (150-375 mg/d). During the first study period (7.5 days), subjects in group A
      received concomitant voriconazole (200 mg every 12 hours); group B received a
      matched placebo. After a washout period (>or=4 days), subjects were crossed over
      to the other treatment regimen. RESULTS: In the 7 subjects who completed both
      regimens, concomitant administration with voriconazole resulted in a 1.7-fold
      increase in mean cyclosporine area under the plasma concentration-time curve
      within a dosage interval (AUC(tau); 90% confidence interval, 1.47 to 1.96).
      Cyclosporine maximum observed plasma concentration (C(max)) and the time to the
      first occurrence of C(max) (t(max)) were not affected in a clinically significant
      manner, but plasma trough concentration (C(min)) was higher in the presence of
      voriconazole than with placebo. The mean increase in cyclosporine C(min) in
      subjects who ceased to participate in the study was 2.48-fold (range, 1.88 to
      3.03). There were 7 subjects who stopped participating in the study during
      voriconazole administration. Six of these subjects discontinued the study for
      reasons that were considered to be drug related, and the majority were
      attributable to increased cyclosporine levels. Although not serious, all
      causality-related adverse events were more frequent during voriconazole
      administration than during placebo administration. CONCLUSIONS: Mean cyclosporine
      AUC(tau) increased 1.7-fold in the presence of voriconazole. Therefore, when
      voriconazole is initiated in patients already receiving cyclosporine, it is
      recommended that the cyclosporine dose be halved and that blood cyclosporine
      concentrations be carefully monitored. When voriconazole is discontinued, blood
      cyclosporine concentrations should be monitored and the cyclosporine dose
      increased, if necessary.

PMID- 11956506
TI  - Pharmacokinetic and pharmacodynamic modeling of humanized anti-factor IX antibody
      (SB 249417) in humans.
AB  - BACKGROUND: SB 249417 is a humanized anti-factor IX/IXa antibody that, on
      administration to rats and monkeys, produces an immediate suppression of factor
      IX activity and prolongation of activated partial thromboplastin times (aPTT).
      OBJECTIVE: Our objective was to establish the pharmacokinetics of SB 249417 and
      to explore its effects on factor IX activity levels and aPTT in humans. METHODS:
      In this phase I, single-blind, randomized, placebo-controlled, parallel-group,
      single intravenous infusion study, individual and mean data from a total of 26
      healthy volunteers at 5 dosing levels were analyzed. A 2-compartment
      pharmacokinetic model was used in the analysis of total SB 249417 concentration
      time profiles. A modified indirect-response model was used, with the total
      concentration indirectly serving as the driving force for the suppression of free
      factor IX concentration (as assessed by factor IX activity). The aPTT was related
      to factor IX activity with a biexponential equation, and a population approach
      was used to generate posterior parameter estimates for the individual fittings.
      RESULTS: Mean parameter estimates from individual fittings are 0.092 L/kg for
      volume of distribution, 0.15 L/kg for steady-state volume of distribution, and
      0.0021 L/kg per hour for systemic clearance. The model described well the factor
      IX activity and aPTT time course in response to SB 249417 at 5 dose levels. The
      estimated half-life of factor IX in blood was 21 hours. CONCLUSIONS: This model
      was stable and robust in fitting both mean and individual data. Endogenous factor
      IX baseline levels and dose were the major determinants of the decline in factor
      IX activity during the infusion period. Thereafter the recovery of factor IX
      activity was governed solely by the endogenous factor IX turnover rate.

PMID- 11956507
TI  - Pharmacokinetic and pharmacodynamic modeling of the antiplatelet and
      cardiovascular effects of cilostazol in healthy humans.
AB  - OBJECTIVE: Cilostazol is an antiplatelet agent with vasodilating properties. It
      has been used to treat patients with peripheral ischemia, such as intermittent
      claudication. We used a pharmacokinetic-pharmacodynamic model to analyze the
      relation between the plasma concentration of cilostazol, the inhibitory effect of
      the drug on platelet aggregation, and the cardiovascular effects of the drug on
      healthy humans. METHODS: A single oral dose of 100 mg cilostazol was administered
      to 20 healthy volunteers. Serial blood sampling and pharmacodynamic measurements
      were performed up to 48 hours thereafter. The effects of cilostazol on platelet
      aggregation, blood pressure, and heart rate were measured during the same period.
      The plasma concentration of cilostazol was measured with a validated HPLC method
      that entailed ultraviolet detection. The time courses of plasma cilostazol
      concentration, platelet aggregation, and cardiovascular effects were analyzed by
      means of pharmacokinetic-pharmacodynamic modeling with the program ADAPT II.
      RESULTS: The plasma concentration-time course followed a 2-compartment model.
      Mean peak concentration was 775 ng/ml approximately 3.65 hours after
      administration of cilostazol. The maximal effect on platelet aggregation was a
      31.14% reduction 6.05 hours after administration. No significant difference in
      systolic blood pressure was found. The maximal increase in heart rate was 13.49%,
      whereas the maximal decrease in diastolic blood pressure was 29.51%. Both peak
      effects were detected approximately 6 hours after administration of the drug.
      Platelet aggregation and cardiovascular effects (change in diastolic blood
      pressure and heart rate) were analyzed with the effect-link sigmoid maximal
      effect model. CONCLUSION: This pharmacokinetic-pharmacodynamic model successfully
      described the relation between plasma concentration of cilostazol and the
      antiplatelet and cardiovascular effects of the drug.

PMID- 11956508
TI  - In vivo and in vitro studies exploring the pharmacokinetic interaction between
      bosentan, a dual endothelin receptor antagonist, and glyburide.
AB  - BACKGROUND: In a clinical trial with patients with chronic heart failure, a
      higher incidence of elevated levels of liver transaminases was observed during
      concomitant treatment with bosentan, a dual endothelin receptor antagonist, and
      glyburide (INN, glibenclamide), a sulfonylurea-type antidiabetic drug, than with
      treatment with bosentan alone. This study was conducted to investigate a possible
      pharmacokinetic interaction between bosentan and glyburide. METHODS: In a
      randomized, 2-way crossover study, 12 healthy volunteers received treatments A
      and B. Treatment A consisted of 125 mg bosentan twice a day for 10 days plus
      concomitant 2.5 mg glyburide twice a day on days 6 to 10. Treatment B consisted
      of 2.5 mg glyburide twice a day for 10 days plus concomitant 125 mg bosentan
      twice a day on days 6 to 10. Plasma concentrations of bosentan and its
      metabolites and of glyburide were measured on days 5 and 10 of treatment A and
      treatment B, respectively. RESULTS: Bosentan reduced the area under the
      concentration-versus-time curve of glyburide approximately 40% (P <.05).
      Glyburide decreased the area under the concentration-versus-time curve of
      bosentan and its metabolites 20% to 30% (P <.05). Results of in vitro experiments
      showed that glyburide is metabolized by cytochrome P450 (CYP) 2C9, 2C19, and 3A4.
      No interaction was observed on the level of serum protein binding. CONCLUSIONS:
      The plasma levels of both bosentan and glyburide were reduced after concomitant
      administration. This finding is consistent with a CYP3A4-inducing potential of
      both drugs. The observed pharmacodynamic interaction between bosentan and
      glyburide in patients with chronic heart failure cannot be explained by a
      pharmacokinetic interaction.

PMID- 11956509
TI  - Cholinergic toxic syndrome by the anticancer drug irinotecan:
      acetylcholinesterase does not play a major role.
AB  - BACKGROUND: The anticancer drug irinotecan induces cholinergic side effects that
      are currently ascribed to the blockade of acetylcholinesterase. This study
      investigated (1) the pattern of acetylcholinesterase activity in patients
      receiving treatment with irinotecan and (2) the relationship between
      acetylcholinesterase activity and plasma concentrations of irinotecan, 7-ethyl-10
      hydroxycamptothecin (SN-38), and SN-38 glucuronide (SN-38G). METHODS: Twenty-five
      patients with advanced colorectal cancer were treated with 250 mg/m(2) irinotecan
      administered by intravenous infusion for 60 minutes. Blood samples were collected
      before drug infusion and at 15 minutes and 45 minutes after the start of drug
      infusion. Blood acetylcholinesterase activity was determined by a colorimetric
      enzymatic assay, and irinotecan, SN-38, and SN-38G concentrations were determined
      in plasma by HPLC. The in vitro effects of irinotecan and other drugs on human
      acetylcholinesterase were also assessed. RESULTS: Compared with basal values, the
      activity of acetylcholinesterase in blood specimens collected during irinotecan
      infusion at 15 minutes (-0.76%) and at 45 minutes (-1.50%) showed no changes. No
      relationships were established between the activity of blood acetylcholinesterase
      at 15 or 45 minutes and plasma concentrations of irinotecan, SN-38, or SN-38G
      measured at the same time points. In vitro, the activity of acetylcholinesterase
      was inhibited by 100-micromol/L irinotecan (-24.8%) and markedly reduced by 1
      micromol/L physostigmine (-86.7%), whereas neither SN-38 nor camptothecin had an
      effect. CONCLUSIONS: Although the use of erythrocyte acetylcholinesterase as a
      surrogate marker of acetylcholinesterase activity in the nervous system has not
      been firmly established, our findings do not support the hypothesis that the
      toxic cholinergic syndrome associated with irinotecan treatment depends on
      acetylcholinesterase blockade.

PMID- 11956510
TI  - Acute effect of L-796568, a novel beta 3-adrenergic receptor agonist, on energy
      expenditure in obese men.
AB  - OBJECTIVE: Our objective was to investigate the thermogenic efficacy of single
      oral doses of the novel beta(3)-adrenergic receptor agonist L-796568 [(R )-N -[4
      [2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]-phenyl]-4-[4-[4
      (trifluoromethyl)phenyl]thiazol-2-yl]-benzenesulfonamide, dihydrochloride] in
      humans. METHODS: Twelve healthy overweight to obese men participated in this 2
      center, 3-period, randomized, placebo-controlled, crossover trial. In each period
      subjects received 250 mg L-796568, 1000 mg L-796568, or placebo. Energy
      expenditure and respiratory quotient were determined by indirect calorimetry;
      blood samples were taken; and ear temperature, heart rate, and blood pressure
      were measured at baseline and during the 4-hour period after administration.
      RESULTS: Energy expenditure increased significantly after the 1000-mg dose (about
      8%) and this was accompanied by an increase in plasma glycerol and free fatty
      acid concentrations. Systolic blood pressure also increased significantly. No
      changes in heart rate, diastolic blood pressure, ear temperature, plasma
      catecholamine, potassium, or leptin were found. CONCLUSIONS: Single-dose
      administration of 1000 mg of the novel beta(3)-adrenergic receptor agonist L
      796568 increased lipolysis and energy expenditure in overweight men. This is the
      first study to show such an effect of beta(3)-adrenergic receptor agonists in
      humans without significant evidence for beta(2)-adrenergic receptor involvement.

PMID- 11956511
TI  - CD4 response is correlated with peak plasma concentrations of indinavir in adults
      with undetectable human immunodeficiency virus ribonucleic acid.
AB  - We retrospectively evaluated correlates of increases in CD4 cell count in
      antiretroviral agent-naive subjects with fewer than 50 copies per milliliter of
      plasma human immunodeficiency virus ribonucleic acid who were participating in a
      study of indinavir, lamivudine, and zidovudine therapy. Pharmacologic data from
      intensive pharmacokinetic studies and baseline patient characteristics were
      evaluated as predictors of the increase in CD4 count from baseline to weeks 24,
      56, and 80. Relations were investigated with regression analysis. Of all
      covariates, maximum plasma concentration (C(max)) of indinavir was significantly
      and uniquely associated with increases in CD4 count from baseline to all end
      points (P =.002 at week 80; n = 20). At week 80, subjects with a C(max) greater
      than the overall group median value of 7 microg/ml had an increase in CD4 count
      of 358 cells/microl versus 197 cells/microl for those with a C(max) less than 7
      microg/ml (P =.006). These data suggest distinct pharmacodynamic relations exist
      for immune reconstitution and suppression of plasma human immunodeficiency virus
      ribonucleic acid. We hypothesize this new finding may be associated with
      expression of P-glycoprotein.

PMID- 11956512
TI  - Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the
      insulin and glucose response in healthy volunteers.
AB  - BACKGROUND: Glyburide (INN, glibenclamide) is a second-generation sulfonylurea
      antidiabetic agent with high potency. We hypothesized that glyburide may be a
      substrate of cytochrome P450 2C9 (CYP2C9), an enzyme that has two low-activity
      amino acid variants-Arg144Cys (CYP2C9*2) and Ile359Leu (CYP2C9*3). We explored
      the impact of these polymorphisms on glyburide pharmacokinetics and the effects
      on insulin and glucose concentrations. METHODS: Twenty-one healthy volunteers who
      represented all possible combinations of the two variant alleles were studied
      (genotypes CYP2C9*1/*1, *1/*2, *2/*2, *1/*3, *2/*3, and *3/*3 ). They received a
      single oral dose of 3.5 mg glyburide followed by 75 g glucose at 1, 4.5, and 8
      hours after administration of glyburide. Glyburide was quantified in plasma by
      reversed-phase HPLC. Venous blood concentrations of glyburide, insulin, and
      glucose were analyzed with a population pharmacokinetic-pharmacodynamic model by
      use of NONMEM statistical software. RESULTS: Pharmacokinetics of glyburide
      depended significantly on CYP2C9 genotypes. In homozygous carriers of the
      genotype *3/*3, total oral clearance was less than half of that of the wild-type
      genotype *1/*1 (P <.001). Correspondingly, insulin secretion measured within 12
      hours after glyburide ingestion was higher in carriers of the genotype *3/*3
      compared with the other genotypes (P =.028), whereas the differences in glucose
      concentrations were not significant. CONCLUSIONS: Carriers of the CYP2C9 variant
      *3 had decreased oral clearances of glyburide. This confirms that glyburide is
      metabolized by CYP2C9. Corresponding differences in insulin plasma levels
      indicated that dose adjustment based on CYP2C9 genotype may improve antidiabetic
      treatment.

PMID- 11956514
TI  - Determination of maximum effect.

PMID- 11956513
TI  - Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level
      of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese
      subjects.
AB  - The effect of the C3435T mutation at exon 26 of the MDR1 gene on the expression
      levels of MDR1 messenger ribonucleic acid (mRNA) was evaluated by means of real
      time polymerase chain reaction in 51 biopsy specimens of duodenum obtained from
      13 healthy Japanese subjects. The mRNA levels of MDR1 were 0.38 +/- 0.15, 0.56 +/
      0.14, and 1.13 +/- 0.42 (mean value +/- SE) in the subjects with the homozygote
      of wild-type allele (C/C), compound heterozygote with mutant T allele (C/T), and
      the homozygote of the mutant allele (T/T), respectively, reasonably explaining
      the lower digoxin serum concentration after administration of a single oral dose
      to subjects harboring a mutant T allele. Good correlation (r =.797; P <.01) was
      observed between the mRNA concentrations of MDR1 and CYP3A4 in the individual
      biopsy specimens. This finding suggested a lower plasma concentration of the
      substrates for CYP3A4 in subjects harboring the C3435T mutation of the MDR1 gene.

PMID- 11956517
TI  - Predictors of survival in older men with AIDS.
AB  - Previous studies indicate that older individuals with AIDS are at increased risk
      for morbidity and death. The purpose of this study was to examine the clinical
      manifestations of male patients older than 45 when they entered HIV care and the
      survival of the older men who had AIDS. A historical, nonconcurrent cohort study
      of HIV-infected men (n = 2583) enrolled in the HIV outpatient program of the
      Medical Center of Louisiana in New Orleans as of January 2000 was conducted. Age
      older than 50, wasting syndrome, cancer, and neutropenia were predictive of
      death. These findings suggest the need to closely monitor older men with AIDS who
      have these conditions and provide appropriate therapies. The significantly higher
      proportions of older men with AIDS at study entry and no reported risk factor
      also indicates the need to target prevention and education efforts at older
      individuals.

PMID- 11956518
TI  - Parkinson's disease primer.
AB  - Parkinson's disease (PD) is a progressive, neurodegenerative disorder
      characterized by the primary motor symptoms of bradykinesia, muscle rigidity,
      resting tremor, and postural instability. PD most often affects people older than
      65, although it does occur at younger ages. The purpose of this article is to
      provide a brief overview of the pathophysiology of PD and a review of current
      literature, assessment and diagnostic techniques, therapeutic interventions, and
      management protocols. Treatment goals are twofold: short-term treatment to
      alleviate symptoms and reverse functional disability and long-term treatment to
      maintain effectiveness and limit pharmacologic complications.

PMID- 11956519
TI  - Nursing assistants' perceptions of their ability to provide continence care.
AB  - More than 50% of all elderly nursing home residents suffer from urinary
      incontinence (UI). Although effective urinary continence programs exist,
      successful implementation continues to be a problem. This qualitative study
      involved seven focus groups of three to seven nursing assistants each (total n =
      31) to examine their perceptions about factors that either promote or inhibit
      continence care. Better cooperation and increased communication emerged as
      factors that would improve teamwork and decrease workload. This article includes
      quotes from individual nursing assistants and a discussion of the factors most
      commonly identified as promoting or inhibiting care. Nursing assistants are
      valuable members of the health care team. Knowing their perceptions should allow
      professional nurses and facility administrators to develop continence programs
      that better meet the needs of both the nursing assistants who implement them and
      the residents for whom they care.

PMID- 11956520
TI  - Comprehensive management of urinary incontinence through quality improvement
      efforts.
AB  - This article provides a comprehensive examination of eight factors to analyze the
      potential and contributing causes of urinary incontinence (UI) in long-term care
      facilities. These factors can guide quality improvement committees to reduce the
      prevalence of UI. The eight factors--evidence-based practice, assessment,
      environment, education, staffing, communication, involvement, and
      evaluation/feedback--were identified through an analysis of 70 quality
      improvement plans developed by Minnesota nursing facilities and substantiated by
      the research literature.

PMID- 11956521
TI  - Hypothyroidism in elderly people.
AB  - Abnormal thyroid function tests are common for older adults, but the clinical
      significance of abnormal results and the need for treatment vary. Nonthyroidal
      illness (eg, low T3 and T4 syndromes) needs to be ruled out before making the
      diagnosis of hypothyroidism. Overt hypothyroidism and myxedema coma always
      require treatment, but treatment of subclinical hypothyroidism is not as clear.
      The purpose of this review article is to summarize existing data in the elderly
      population on the etiology, diagnosis, and management of overt hypothyroidism and
      subclinical hypothyroidism.

PMID- 11956522
TI  - Gerontologic nurse practitioner preceptor guide.
AB  - Geriatric nurse practitioners (GNPs) often serve as clinical preceptors for nurse
      practitioner students. The Nursing Interest Group of the John A. Hartford
      Foundation's Geriatric Interdisciplinary Team Training Program recognized a need
      for a condensed guide that clarifies the role of a GNP preceptor. This guide uses
      information from the literature to clarify the role of the preceptor, offer
      suggestions for clinical teaching, provide guidance to determine expectations for
      student performance, and delineate the progression of a nurse practitioner
      student. This article reviews the contents of the guide and offers suggestions
      for its use in clinical practice.

PMID- 11956523
TI  - Assessment for depression among nursing home elders: evaluation of the MDS mood
      assessment.
AB  - The 30-item Geriatric Depression Scale (GDS), the GDS Short Form, and the Mood
      Assessments from the Minimum Data Set versions 1 and 2 were completed for 50
      nursing home elders. The purpose of the study was to evaluate agreement among
      these measures of depression, with the GDS considered the gold standard. Although
      the GDS Short Form performed highly consistently with the GDS, the correlations
      of the MDS mood assessments with the GDS were relatively low. The results are
      discussed in the context of the characteristics that surround the use of the MDS,
      and recommendations are made for improving methods of detecting depression among
      nursing home elders.

PMID- 11956524
TI  - The connection between drugs and falls in elders.

PMID- 11956525
TI  - Fraud and abuse--an overview.

PMID- 11956526
TI  - Duplicate publications in peer-reviewed journals.

PMID- 11956527
TI  - Duplicate publication in the field of otolaryngology-head and neck surgery.
AB  - OBJECTIVE: This study establishes the approximate prevalence and patterns of
      duplicate publication in the medical literature in the specialty of
      otolaryngology-head and neck surgery. STUDY DESIGN AND SETTING: All of the
      authors and articles published in the American Medical Association Archives of
      Otolaryngology-Head and Neck Surgery were identified and listed for an 8-year
      period. During this time, 1965 authors published 1082 articles in the Archives,
      and this same set of authors published a total of almost 50,000 articles during
      the 12-year period between January 1977 and December 1988. Of the same set of
      1965 authors, we picked 1000 at random and found that they had published a total
      of 24,353 articles. The titles of these articles were then screened for similar
      titles, and when similarities were noted, the complete articles were obtained
      when possible and compared for the degree and pattern of duplicate publication.
      RESULTS: Of the 1000 authors studied, we found that 228 authors had published 938
      articles with similar titles. We were able to obtain the full copy of 886 (94%)
      of the 938 articles in question, which were written by 226 (99%) of the 228
      authors. We found that in the case of 25 authors, there was no duplication
      despite the similar titles, but in the case of 201 (20% of the 1000) authors, 644
      articles were published with some degree of duplication (1.8% duplication rate).
      CONCLUSIONS: The most common duplicate publication involves sequential
      publication of very similar data and conclusions. Duplicate publications failed
      to reference prior articles by the same author 32% of the time or referenced the
      prior articles only partially (11% of the time). Artificial segmentation of a
      single study into multiple arbitrary segments composed 20% of the duplicate
      publication. Duplicate publication across different specialties was noted to
      account for 4% of the instances. Most of the authors duplicated only once or
      twice, and most duplicators do reference their prior publications. SIGNIFICANCE:
      Duplicate publication is an example of inappropriate academic conduct. Because it
      tarnishes the reputation of the duplicating author and represents an unfair
      practice in terms of displacing the work of others, efforts should continue to
      educate authors, particularly young academicians, to avoid the practice of
      duplicate publication.

PMID- 11956528
TI  - Sleepy driving: accidents and injury.
AB  - OBJECTIVE: The study goals were to evaluate the associated risks of driving and
      to assess predictors of accidents and injury due to sleepiness. STUDY DESIGN: A
      cross-sectional Internet-linked survey was designed to elicit data on driving
      habits, sleepiness, accidents, and injuries during the preceding 3 years.
      Statistical analysis included logistic models with covariate-adjusted P values of
      <0.01 (odds ratios and 95% confidence intervals or limits). Independent accident
      predictors were sought. RESULTS: Responses from 10,870 drivers were evaluated.
      The mean +/- SD age was 36.9 +/- 13 years; 61% were women and 85% were white. The
      Epworth Sleepiness Scale overall baseline score was 7.4 +/- 4.2 (for drivers with
      no accidents) and ranged to 12.7 +/- 7.2 (for drivers with > or = 4 accidents) (P
      = < 0.0001). Twenty-three percent of all respondents experienced > or = 1
      accident. Among respondents who reported > or = 4 accidents, a strong association
      existed for the most recent accident to include injury (P < 0.0001). Sleep
      disorders were reported by 22.5% of all respondents, with a significantly higher
      prevalence (35%, P = 0.002) for drivers who had been involved in > or = 3
      accidents. CONCLUSION: Factors of sleepiness were strongly associated with a
      greater risk of automobile accidents. Predictors were identified that may
      contribute to accidents and injury when associated with sleepiness and driving.

PMID- 11956529
TI  - Final validation of the Pediatric Tracheotomy Health Status Instrument (PTHSI).
AB  - OBJECTIVE: We sought to describe the development and final testing of an
      instrument designed to evaluate the impact of tracheotomy on the health-related
      quality of life of affected families in whom a child has had a tracheotomy (the
      Pediatric Tracheotomy Health Status Instrument [PTHSI]). STUDY DESIGN: This cross
      sectional study designed to analyze a disease-specific health status instrument
      to establish validity and reliability. RESULTS: The PTHSI was initially pilot
      tested in 130 families during a 3-month period from September through November
      2000. After initial analysis and revision, from January 2001 through July 2001,
      154 different families completed the revised instrument. The overall Cronbach's
      alpha coefficient for the instrument was 0.91, with domain-specific coefficients
      ranging from 0.66 for physical symptoms to 0.87 for caregiver stress and coping.
      Specific criterion validity analysis produced a Pearson correlation coefficient
      of 0.8 (P < 0.0001). Construct validity testing via Wilcoxon matched sum testing
      suggested statistically significant differences between subpopulations (P <
      0.001). CONCLUSION: After initial testing and revision of the PTHSI, final
      instrument administration and analysis reveal the instrument to be valid and
      reliable. Future studies are planned to evaluate its responsiveness in
      longitudinal application.

PMID- 11956530
TI  - Airway complications of infant botulism: ten-year experience with 60 cases.
AB  - OBJECTIVE: The study goal was to understand the incidence, etiology, and
      management of airway complications in infant botulism. METHODS: We conducted a
      retrospective review of the period from January 1, 1987, to December 31, 1997.
      SETTING: Urban tertiary care children's hospital. RESULTS: Of 60 children with
      infant botulism, 37 (61.7%) required endotracheal intubation for a mean of 21
      days. No patient required a tracheostomy. Airway complications (stridor,
      subglottic stenosis, granuloma formation) occurred in 5 (13.5%) of 37 patients,
      with 3 requiring surgical bronchoscopy. Of the 37 children, 14 (37.8%), including
      4 with airway complications, had endotracheal tube leak pressures recorded. In 3
      (50%) of 6 patients with measured leak pressures of greater than 40 cm H2O,
      airway complications developed. Complications did not develop in patients with
      leak pressures of less than 20 cm H2O. No correlation between length of
      intubation and complications could be established. CONCLUSION: Airway
      complications in infant botulism may be accompanied by high leak pressures and
      can be managed with endoscopic techniques. The study data suggest that leak
      pressures should be measured on a regular basis and maintained at less than 20 to
      25 cm H2O. A prospective trial to study this issue is warranted. Tracheotomy is
      not routinely necessary. A high index of suspicion, early diagnosis, and prompt
      intervention are required for the optimal management of airway complications in
      infant botulism.

PMID- 11956531
TI  - Tracheal bronchus: classification, endoscopic analysis, and airway management.
AB  - OBJECTIVE: Tracheal bronchus (bronchus suis) is an unusual congenital anomaly in
      which the right upper lobe has its origin in the trachea rather than distal to
      the carina. We sought to analyze the anatomy, presentation, and airway management
      principles of tracheal bronchi, and we present the first endoscopically
      documented tracheal diverticulum. STUDY DESIGN/METHODS: Retrospective case
      series. RESULTS: The tracheal bronchus is located at the junction of the mid and
      distal thirds of the right lateral trachea, is more common in males and children
      with other congenital anomalies, and may be associated with right main bronchus
      stenosis. Bronchoscopy provides a clear definitive view of the anomaly, which we
      found in 5 children during a 12-year period (0.5% of pediatric bronchoscopy
      procedures). We illustrate 3 types of tracheal bronchi: (1) vestigial tracheal
      diverticulum (newly described), (2) high apical lobe, and (3) fully developed
      supranumerary aerated tracheal bronchus. Endoscopic documentation of each type is
      presented. Children with tracheal bronchi may present with stridor, cough, and/or
      recurrent right-sided pneumonia and/or to have foreign body aspiration ruled out.
      Treatment is based on the severity of symptoms and ranges from observation to
      right upper lobectomy. CONCLUSIONS: Otolaryngologists should be aware of the
      tracheal bronchus, to include classification, endoscopic analysis, and airway
      management of this uncommon anomaly. Bronchoscopy with selected radiographic
      imaging allows the otolaryngologist to fully evaluate the child with a tracheal
      bronchus and to present timely therapeutic options.

PMID- 11956532
TI  - Continuous gentamicin therapy using an IntraEAR microcatheter for Meniere's
      disease: a retrospective study.
AB  - OBJECTIVES: The study goals were to evaluate the safety and effectiveness of
      continuous gentamicin therapy (CGT) in the treatment of Meniere's disease and to
      evaluate the effect of flow rate. STUDY DESIGN: In a retrospective study,
      physicians who were known to have used CGT in the treatment of Meniere's disease
      were asked to report patient information on a standardized data collection form.
      RESULTS: In patients treated with low-flow CGT, vertigo was eliminated or
      substantially controlled in 90%, tinnitus was improved in 69%, pressure was
      improved in 77%, hearing was worse in 23%, and vestibular function was ablated in
      only 14% of patients. CONCLUSION: On the basis of an average 10-month follow-up
      period, of the methods currently available to treat Meniere's patients with
      gentamicin, low-flow CGT seems to provide an excellent combination of vertigo
      control and tinnitus and pressure improvement, with a relatively low risk to
      hearing and vestibular function. SIGNIFICANCE: The clinical use of low-flow CGT
      appears to be justified based on these data.

PMID- 11956533
TI  - Speech recognition in background noise of cochlear implant patients.
AB  - OBJECTIVES: The performances of adult patients using Spectral peak (Nucleus 22 or
      Nucleus 24 patients) or Continuous Interleaved Sampling or Advanced Combination
      Encoder (Clarion patients) were evaluated in their ability to perform in quiet
      and in 2 levels of background noise. PATIENTS AND METHODS: Ninety-six patients
      were tested with the City University of New York Sentences presented at 70 dB in
      quiet and at signal-to-noise ratios (SNR) of +10 and +5 dB. Patients were scored
      on the number of words perceived correctly. RESULTS: Scores were different at
      each condition (P < 0.05): 88% words correct in quiet, 73% correct at an SNR of
      +10 dB, and 47% correct at an SNR of +5 dB. Linear regression analysis found no
      significant correlation between test score and age at implantation or time using
      the implant. A weak negative correlation was found between years of hearing loss
      and score. CONCLUSION: Competing noise interferes with comprehension of connected
      speech for most cochlear implant patients.

PMID- 11956534
TI  - Tympanosclerosis: long-term hearing results after ossicular reconstruction.
AB  - OBJECTIVE: The study goal was to analyze long-term hearing results and factors
      likely to affect outcome after ossicular reconstruction in patients with
      tympanosclerosis, particularly tympanosclerotic stapes fixation. METHODS: We
      conducted a retrospective chart review of the past 10 years. The short- and long
      term (up to 9(1/2) years) hearing results of first-stage and second-stage
      operations for middle ear tympanosclerosis in 203 consecutive patients, performed
      in a tertiary referral otologic private practice, are presented. There were 160
      tympanoplasties and 43 tympanoplasties with mastoidectomy performed, with
      ossicular fixation secondary to tympanosclerosis in 135 cases. Of these 203,
      42.9% were primary cases, with the majority being planned second-stage or
      revision procedures. RESULTS: The average preoperative air-bone gap (ABG) was
      30.9 dB. The average short-term postoperative ABG was 17.4 dB with closure of the
      ABG within 20 dB in 64.6%. The success rate (ABG < or = 20 dB) for patients with
      ossicular fixation was 65.3%. Partial sensorineural hearing loss occurred in 1.0%
      of the patients, and none experienced profound sensorineural hearing loss (dead
      ears). There was no statistically significant change from short-term to long-term
      follow-up in either ABG or air PTA, with mean differences of only 0.3 and 2.0 dB,
      respectively. The mean time to the last follow-up was 1.6 years. CONCLUSION:
      Ossicular reconstruction in individuals with tympanosclerosis can yield
      satisfactory, lasting hearing results with a low incidence of complications and
      no dead ears.

PMID- 11956535
TI  - Sympathetic cochleolabyrinthitis in revision stapedectomy surgery.
AB  - OBJECTIVE: The purpose of this study was to determine whether revision
      stapedectomy could precipitate sensorineural hearing loss in the contralateral
      ear. METHODS: We conducted a retrospective review of 148 patients undergoing
      primary or revision stapedectomy at an academic, tertiary care facility. RESULTS:
      Stapedectomy resulted in significant improvements in mean air conduction
      thresholds in the ipsilateral ear. Overall, there were no significant changes in
      either the air or bone conduction values of the contralateral ear. Two patients
      demonstrated a >20-dB decline in speech reception threshold and/or >20% decrease
      word recognition in the contralateral ear. Both of these patients demonstrated
      the decline only after revision surgery. CONCLUSION: Revision stapedectomy is on
      rare occasions associated with hearing loss in the contralateral ear.
      Contralateral hearing loss after revision stapedectomy may be due to sympathetic
      cochleolabyrinthitis.

PMID- 11956536
TI  - The temporal course of adenovirus-mediated gene transfer in the rat larynx.
AB  - OBJECTIVE: Polypeptide growth factors have important influences on wound-healing
      and scar tissue formation. Specific growth factors or their inhibitors may
      potentially decrease scar tissue formation and prevent subglottic stenosis. Gene
      transfer using recombinant adenovirus may be an ideal method to mediate
      endogenous production of growth factors to inhibit fibrosis. STUDY DESIGN: The
      study incorporated adenovirus-mediated transduction of normal and stenotic rat
      larynges and histologic analysis of the sequential expression of a beta
      galactosidase marker gene over time. SETTING: The study was conducted at the
      animal care facility of an academic children's hospital. RESULTS: We report
      successful transduction in normal and injured rat larynx with peak expression of
      beta-galactosidase at 2 days after transduction and almost complete disappearance
      by 7 days. There appeared to be an early inflammatory response to the viral
      injection, but at 7 and 14 days after injection (transduction) the uninjured rat
      larynges resumed a normal histologic appearance. All distant sites stained
      negative for beta-galactosidase. CONCLUSION: Recombinant adenovirus-mediated gene
      transfer is feasible in the rat larynx with transient duration and limited
      toxicity. SIGNIFICANCE: Adenovirus-mediated gene transfer has the potential to
      deliver growth factors that modulate wound healing and inflammation in the larynx
      by inhibiting fibrosis.

PMID- 11956537
TI  - Expression of the proto-oncogene eIF4E in inflammation of the oral cavity.
AB  - OBJECTIVE: eIF4E (4E) is elevated in 100% of head and neck squamous cell
      carcinoma (HNSCC) and in premalignant lesions of the larynx. However, it is not
      elevated in normal mucosa. In this study, we hypothesize that 4E is not
      significantly elevated in inflammation unlike its expression in premalignant
      lesions of the oral cavity. STUDY DESIGN: Biopsies from the oral cavity were
      divided into 5 groups: (1) normal mucosa, (2) chronic inflammation, (3) mild
      dysplasia from leukoplakic lesions, (4) mild dysplasia in surgical margins of
      patients with HNSCC, and (5) HNSCC. Immunohistochemical qualitative analysis was
      then performed. RESULTS: None of the 15 specimens in group 1 and 100% of the 15
      specimens in group 5 expressed 4E. Of the 29 specimens in group 2 only 4/29 (13%)
      overexpressed 4E compared with 10/31 (32%) in group 3 and 9/21 (42%) in group 4.
      There was a significant difference between groups 2 and 3 and groups 2 and 4 (P <
      0.0001 and P < 0.003 respectively) but no significant difference between groups 1
      and 2 (P = 0.13) and between groups 3 and 4 (P = 0.30). CONCLUSION: 4E is not
      significantly elevated in inflammation of the oral cavity thus fulfilling one of
      the criteria that biomarkers require to be useful in a clinical setting.

PMID- 11956538
TI  - Microsatellite analyses of loci at 7q31.3-q36 reveal a minimum of two common
      regions of deletion in nasopharyngeal carcinoma.
AB  - OBJECTIVE: Our goal was to better define the extent and specificity of deletion
      in the 7q32-qter chromosomal region in nasopharyngeal carcinoma (NPC). DESIGN AND
      SETTING: Polymerase chain reaction-based deletion analysis was performed on DNA
      samples from 24 paired NPCs and corresponding germlines using 13 microsatellite
      markers mapped to chromosome subbands 7q31.3-q36. RESULTS: Loss of heterozygosity
      of at least 1 marker in this interval was found in 18 (75%) of 24 tumor
      specimens. Particularly frequent allelic losses were identified at 5 loci: D7S495
      (46%), D7S509 (42%), D7S500 (45%), D7S631 (30%), and D7S514 (35%). Two shortest
      regions of overlap could be identified in this interval, although the most common
      shortest region of overlap appeared to lie around D7S500 between but not
      including D7S631 and D7S495, on chromosome subband 7q32. CONCLUSION: These
      results suggest that at least 2 putative tumor suppressor genes important in the
      pathogenesis of NPC are present in the examined interval, an interval that has
      also been found to harbor deletions in breast and prostate carcinomas.

PMID- 11956539
TI  - Octogenarian free flap reconstruction: complications and cost of therapy.
AB  - OBJECTIVE: The study goal was to document the reliability, incidence of
      complications, and cost of therapy for patients older than 80 years who undergo
      microvascular head and neck reconstruction. PATIENTS AND METHODS: Thirteen
      octogenarians underwent free flap reconstruction of defects resulting from the
      treatment of head and neck cancer at an academic tertiary care medical center.
      The incidence of medical and reconstructive complications and the cost of
      hospitalization were compared with those for 99 younger patients who were treated
      during the same time period. RESULTS: There were no cases of free flap failure or
      significant reconstructive complications in the octogenarians. The incidence of
      medical complications was 62% in the octogenarians and 15% in the younger
      patients. The average cost of therapy was $54,702 per octogenarian patient
      compared with $30,397 per younger patient. The increased incidence of medical
      complications and increased cost arose primarily from an increased severity of
      preoperative systemic illness in the octogenarians. However, controlling for
      comorbidity did not eliminate the discrepancy in medical complications between
      the octogenarians and the younger patients. CONCLUSIONS: Although microvascular
      head and neck reconstruction in the elderly is very reliable, the incidence of
      medical complications and the cost of therapy are significantly increased in
      octogenarians.

PMID- 11956541
TI  - Argon beam coagulation for post-tonsillectomy hemostasis.
AB  - OBJECTIVE: The study goal was to evaluate the effectiveness of argon beam
      coagulation (ABC) in the prevention of post-tonsillectomy hemorrhage. ABC
      provides monopolar coagulation by arcing ionized argon gas to the target tissue;
      it is not a laser. METHODS: Two consecutive studies were performed as follows. In
      the first, a retrospective analysis of post-tonsillectomy bleeding in 344
      patients was conducted. Final tonsil fossa hemostasis was achieved with ABC (257
      patients) or with electrocoagulation (EC) (87 patients). In the second, a
      prospective, randomized, patient-blind study of post-tonsillectomy bleeding was
      conducted in 88 patients. Final hemostasis was achieved using ABC in one fossa
      and EC in the other fossa, with the sides chosen at random. RESULTS: Post
      tonsillectomy hemorrhage was defined as the expectoration of fresh blood, as
      opposed to blood-streaked saliva. The rates of bleeding for the 2 studies were as
      follows. In study 1 for EC, 20% for adults, 6.5% for children, and 10.3% for
      total; for ABC, 4.7% for adults, 0.6% for children, and 1.9% for total. In study
      2 for EC, 19.2% for adults, 1.6% for children, and 6.8% for total; for ABC, 7.7%
      for adults, 0.0% for children, and 1.1% for total. The rates of hospital
      admission for observation or reoperation to treat the bleeding in study 1 for EC
      were 8% for adults, 6.5% for children, and 6.9% for total; for ABC, 1.2% for
      adults, 0.6% for children, and 0.7% for total. Corresponding rates for study 2
      for EC were 15.4% for adults, 1.6% for children, and 5.7% for total; for ABC,
      3.8% for adults, 0.0% for children, and 1.1% for total. CONCLUSION: ABC is more
      effective than EC for hemostasis after tonsillectomy. The costs of ABC use vs the
      savings achieved from reduced bleeding are discussed.

PMID- 11956540
TI  - Does dexamethasone with preemptive analgesia improve pediatric tonsillectomy
      pain?
AB  - OBJECTIVE: The study goal was to determine whether the combination of
      dexamethasone with preemptive analgesia has an additive effect in further
      improving recovery. STUDY DESIGN: We conducted a prospective, randomized, double
      blinded trial of 50 children undergoing tonsillectomy at a university ambulatory
      surgery center. One study group received 1 intravenous dose of dexamethasone, and
      another group received 1 dose of saline solution. All patients received tonsillar
      fossa injections of ropivacaine plus clonidine before tonsil excision. RESULTS:
      The 2 study groups were similar in main outcome measurements. Pain intensity and
      quality of life were not statistically different between the groups. There was a
      small trend to less trismus and less cumulative codeine use in the steroid group.
      Overall, there was a very low incidence of nausea and vomiting in both groups,
      which may have been due to the preemptive analgesia. CONCLUSION: Dexamethasone
      does not significantly improve the morbidity of pediatric tonsillectomy when
      preemptive analgesia with ropivacaine and clonidine is used concurrently.

PMID- 11956542
TI  - Fatality after an injection of Bicillin into the tonsillar fossa during an
      adenotonsillectomy.

PMID- 11956543
TI  - Traumatic optic neuropathy after posterior ethmoidal artery ligation for
      epistaxis.

PMID- 11956544
TI  - Neck mass as primary manifestation of multiple myeloma originating in the thyroid
      cartilage.

PMID- 11956545
TI  - Laryngeal amyloidosis with airway obstruction.

PMID- 11956546
TI  - Matthew Turner: surgeon-apothecary of eighteenth-century Liverpool. His life and
      background.

PMID- 11956547
TI  - Clifton Wintringham of York (1689-1748): an early medical epidemiologist.

PMID- 11956548
TI  - The autobiography of a Renaissance enigma, Jerome Cardan (1501-1576).

PMID- 11956551
TI  - Jivaka, physician to the Buddha.

PMID- 11956550
TI  - Alphonse Laveran (1845-1922): discoverer of the malarial parasite and Nobel
      laureate, 1907.

PMID- 11956552
TI  - Pien Chueh, the Chinese god of medicine.

PMID- 11956553
TI  - Dr R H Bakewell wielded a ready pen.

PMID- 11956554
TI  - A dead disease, as illustrated by the illness of Georgiana, Duchess of
      Devonshire.

PMID- 11956556
TI  - Was Mozart's final illness preceded by a gathering storm?

PMID- 11956557
TI  - Retraction of article: Ramoutsaki IA. Non-Greek doctors involved in the
      nineteenth-century revolutions in Crete (Journal of Medical Biography 2000; 8:
      117-122).

PMID- 11956559
TI  - [Capacitating action of GABA and progesterone in spermatozoa of human and guinea
      pig in vitro].
AB  - This study was designed to investigate whether GABA is involved in the
      capacitation effect and hyperactivated motility (HAM). Spematozoa from fertile
      men and retired guinea pigs were washed in modified BWW of 45% 90% Percoll
      gradient with 26 mg BSA/ml and in low Ca(2+)-MCM of 30%-55%-85% Percoll gradient
      (approximately 23 micromol/L Ca(2+)) respectively. The samples were preincubated
      for 2 h under 5% CO2 in air at 38.5 with or without GABA, progesterone (P(4)),
      GABA(A) receptor agonists or antagonists, and then exposed to 1 micromol/L (for
      human) or 5 micromol/L (for guinea pigs) calcium ionophore A 23187 for 15 min.
      The capacitation effect and HAM were assessed by using the chlortetracycline
      (CTC) staining method and phase-contrast microscopy. Motility was 80% 85% after
      all additions. The results showed that addition of GABA or P(4) at 5 micromol/L
      to the incubation medium resulted in a significant increase in the sum of B
      (characteristic of capacitated cell) and AR (acrosome recation) pattern (65.9%
      and 61.7% respectively), corresponding to capacitated spermatozoa in human, as
      compared to the control (37.3%). Likewise, the capacitating effect of GABA on
      spermatozoa in guinea pigs showed a concentration-dependent increase from 1 to 10
      micromol/L(AR: 27.0 +/- 1.9% to 51.6 +/-2.8%). In addition, P(4) potentiated the
      capacitating effect of GABA when combined with GABA in the capacitation stage.
      The capacitating effect of GABA was mimicked by a GABAA receptor agonist
      muscimol. However, this effect was completely blocked by a GABA(A) receptor
      antagonist (-)-bicuculline and a GABA(A)/Cl(-) receptor antagonist picrotoxin.
      Furthermore, GABA markedly increased the HAM of P(4) on guinea pig spermatozoa,
      which was mediated obviously by the influx of extracellular Ca(2+) because the
      GABA-induced AR could be prevented by EGTA. These results indicate that GABA and
      P(4) are involved in the capacitation of spermatozoa in both human and guinea
      pigs through a GABA(A) receptor-mediated mechanism.

PMID- 11956560
TI  - [GABA inhibits progesterone production of luteal cells of rat ovary].
AB  - In the present work we report that GABA inhibits progesterone production and
      increases the amount of hydroxyl radical in cultured rat luteal cells. The
      inhibitory effect of GABA on progesterone production may be mediated by adenylate
      cyclase system and GABA(A) receptor, but not through protein synthesis pathway.

PMID- 11956561
TI  - [Interleukin-2 stimulates the proliferation of cultured RC-4B/C pituitary adenoma
      cell line].
AB  - The aim of the present study was to investigate whether interleukin-2 (IL-2) is
      involved in the proliferation control of the cultured RC-4B/C cell, which is a
      derived pituitary adenoma cell line of the rat. The level of cell proliferation
      was estimated by assessing (3)H-thymidine ((3)H-TdR) incorporation rate. IL-2 (10
      1000 U/ml) significantly stimulated (3)H-TdR incorporation into the cell line in
      a dose-dependent manner. Specific PTK inhibitor tyrphostin (1 micromol/L)
      suppressed RC-4B/C cell proliferation and blocked the effect of IL-2 on RC-4B/C
      cells. After the PKA signaling pathway was inhibited by specific PKA inhibitor H
      9 (1 micromol/L), the proliferation rate of RC-4B/C cells increased
      significantly. H-9 also enhanced the stimulation of IL-2 on RC-4B/C cell growth.
      Anti-estrogen tamoxifen (1 micromol/L) had no significant effect on the action of
      IL-2 on the proliferation of RC-4B/C cells. In conclusion, it is suggested that
      IL-2 modulates the proliferation of the cultured RC-4B/C pituitary adenoma cell
      line, and the action is closely related with the PTK and PKA signaling pathway.

PMID- 11956562
TI  - [Effects of bFGF and BDNF on the cells of injured adult mouse olfactory
      epithelium in vitro].
AB  - Olfactory epithelium (OE) is unique in the adult nervous system for it produces
      new neurons throughout life. The cultured cells of adult mouse OE in vitro were
      studied by histochemistry and immunocytochemistry techniques, and the results
      showed that they were neurons as up to 50% of the bipolar cells were
      immunopositive to NF, NSE, MAP2, OMP and tau. The effects of basic fibroblast
      growth factor (bFGF) and brain-derived neurotrophic factor (BDNF) in OE medium
      with different concentration serum on OE cell number and development of cell
      processes were also observed. The results showed that the combination of bFGF and
      BDNF added to 10% and 5% serum OE medium increased the bipolar cell number and
      percentage, stimulated the process outgrowth of bipolar cells, and decreased the
      numbers of giant cells and fusiform cells. The effects of the combination of bFGF
      and BDNF in the 10% serum OE medium were more significant than those of bFGF and
      BDNF applied alone; and the effects of neurotrophic factors in the 10% serum OE
      medium were more significant than those observed in the 5% serum OE medium.

PMID- 11956563
TI  - [Plasmid pcDNA3 enhances Ca(2+) transport of sarcoplasmic reticulum in ischemic
      skeletal muscle of rats].
AB  - The effects of plasmid pcDNA3 on Ca(2+) transport of sarcoplasmic reticulum (SR)
      in ischemic skeletal muscle was investigated. The results show that Ca(2+)
      transport (including Ca(2+) uptake and Ca(2+) release) rate of SR in ischemic
      skeletal muscle was markedly increased compared with that in non-ischemic muscle
      (P<0.01 or P<0.05). After plasmid pcDNA3 bound to the DNA binding proteins of SR,
      Ca(2+) transport of SR was further increased. The results suggest that the effect
      of plasmid DNA on the ability of Ca(2+) transport in SR of ischemic skeletal
      muscle is the same as is observed in normal skeletal muscle. The
      pathophysiological significance of the present finding deserves further
      exploration.

PMID- 11956565
TI  - [Melatonin influences the release of endogenous opioid peptides in rat
      periaqueductal gray].
AB  - The present study was undertaken to explore central mechanisms underlying the
      analgesic effect of melatonin. Push-pull perfusion technique and radioimmunoassay
      were used to observe the changes in the contents of beta-endorphin (beta-Ep) and
      leucine-enkephalin (L-EK) in the perfusate from the rat periaqueductal gray (PAG)
      after administration of melatonin. 30  50 min after an intraperitoneal injection
      of melatonin (110 mg/kg), the beta-Ep content in the perfusate was increased
      significantly, while the L-EK content was not changed. Pain threshold was
      measured using the warm water tail-flick test during the push-pull perfusion of
      the PAG. It was found that the rat pain threshold was increased significantly 40
      min after the intraperitoneal injection of melatonin (110 mg/kg). The results
      suggest that melatonin may promote the release of beta-Ep in the PAG, which may
      be one of the mechanisms of the analgesic effect of melatonin.

PMID- 11956566
TI  - Basic fibroblast growth factor increases nitric oxide and endothelin production
      in rat aorta.
AB  - The study was undertaken to investigate the effect of basic fibroblast growth
      factor (bFGF) on aortic production of nitric oxide (NO) and endothelin of aorta
      in spontaneously hypertensive rats (SHR) and WKY rats. Rat aortas were cut into
      vessel slices and incubated with 10 or 100 ng/ml bFGF for 6 hours. Nitric oxide
      synthase (NOS) activity in aortic slices and contents of NO(-)(2) and endothelin
      in the medium were determined. The results showed that NOS activity in aortic
      slices of SHR was 17.6% lower than that of WKY (P<0.01). NO(-)(2) and endothelin
      contents in the medium of SHR aortic slices were 59.7% lower and 37.4% higher
      than those of WKY aortic slices. Upon the exposure of low and high doses of bFGF,
      NOS activity in the aorta of SHR was increased by 29.7% and 59.6% (both
      P<0.01),respectively, while the NO(-)(2) contents in the medium were increased
      respectively by 28.2% (P<0.05) and 70.5% (P<0.01). Aortic endothelin production
      was increased by 24.1% and 44.5% (both P<0.01) respectively while the NOS
      activity in the aorta of WKY was increased by 24.4% and 53.7% (both P<0.01). NO(
      )(2) contents in the medium were augmented by 18.8% (P<0.05)and 25.9% (P<0.01),
      respectively. Aortic endothelin production was increased by 84.1% and 93.1% (both
      P<0.01). It is concluded that bFGF may modulate the production of NO and
      endothelin in both SHR and WKY rats.

PMID- 11956564
TI  - [Distinct structural bases of the immunoregulatory and central analgesic effects
      of IFNalpha].
AB  - Interferon-alpha (IFNalpha), a cytokine, is also an analgesic molecule. There is
      significant cross reactivity between IFNalpha and anti-opioid sera, suggesting a
      strong antigenic relatedness between human IFNalpha molecules and opioid
      peptides. Different structural basis of the immunoactivity and analgesic effect
      of IFNalpha can be demonstrated by different reactivities of the two reactions
      towards different mutants of IFNalpha obtained by using the site-directed
      mutagenesis. When the 129th Tyr residue of human IFNalpha was mutated to Ser, the
      immunoactivity of the mutant almost disappeared, while the strong analgesic
      activity still persisted, which could be blocked by naloxone. These results
      indicate that there exist distinct domains in the IFNalpha molecule, which
      mediate immune and analgesic effects differentially, and that the receptor
      mechanism underlying immune and analgesic effects of IFNalpha may be different.

PMID- 11956568
TI  - [Ischemic preconditioning reduces cardiomyocytic apoptosis in rabbit heart in
      vivo].
AB  - The effects of ischemia-reperfusion (IR) and ischemic preconditioning (IP) on
      hemodynamics, epicardial electrography, myocardial infarct size, cardiomyocytic
      apoptosis and gene proteins involving apoptosis (Fas, Bcl-2 and Bax) were
      observed in aneasthetized rabbit myocardium. The results are as follows. (1)
      During ischemia-reperfusion, heart rate, arterial blood pressure and myocardial
      oxygen consumption were reduced progressively. The epicardial electrographic ST
      segment was elevated significantly during ischemia (P<0.001)and recovered to the
      baseline during reperfusion. (2) The infarct size occupied 57.7+/-2.0% of the
      ischemic myocardium in IR group while IP reduced the infarct size to 27.7+/-1.5%
      (P<0.01). (3) DNA ladder pattern of ischemic myocardium was revealed by agrose
      gel electrophoresis in IR group while it was not found in IP group. Apoptotic
      cardiomyocytes were sparse within the ischemic myocardium at risk in IP as
      compared with those in IR heart. Apoptosis rate of the ischemic myocardium from
      IR and IP groups detected by flow cytometry was 11.2+/-0.4% and 6.35+/-0.2%
      (P<0.01), respectively. (4) Fas and Bax protein expression in the ischemic
      myocardium of IR and IP groups was elevated as compared with those in non
      ischemic myocardium group (P<0.05). The Fas protein expression of IR group was
      higher than that of IP group (P<0.05). Bcl-2/Bax ratio of IR group was lower than
      that in non-ischemic myocardium (P<0.01). From the results, it is suggested that
      IP decreases cardiomyocytic apoptosis induced by IR and this action is mediated
      by the reduction of Fas protein expression.

PMID- 11956567
TI  - Modulation of circadian rhythm of discharges of suprachiasmatic nucleus neurons
      in rat hypothalamic slices by melatonin.
AB  - Spontaneous firing of suprachiasmatic nucleus (SCN) neurons and the effect of
      melatonin (MEL) were examined in hypothalamic slices made from pinealectomized
      rats or from the rats exposed to constant light. The results are as follows. (1)
      Under normal light cycle (light  dark=12  12), SCN neurons displayed a circadian
      rhythm in spontaneous discharges. A peak about 8.3 Hz was presented at CT
      (circadian time) 6  8 and a trough about 3.8 Hz at CT18  20. The circadian rhythm
      persisted after pinealectomy, but disappeared after constant light exposure. (2)
      The response of SCN neurons to MEL was mainly inhibitory. Under normal light
      exposure, the inhibitory proportion was higher during the subjective day with the
      largest proportion of about 42% at CT8  10, and was lower during the subjective
      night with the largest proportion of about 26% at CT22  24. Under both constant
      light exposure and pinealectomy, the circadian rhythm of the response of SCN
      neurons to MEL disappeared. (3) The inhibitory effect of MEL on spontaneous
      discharges of SCN neurons was blocked by ML-1 receptor antagonist luzindole, but
      not by ML-2 receptor antagonist prazosin. The above results suggest that pineal
      gland, as a regulator of the organization of circadian rhythm, regulates the
      circadian rhythm of SCN neurons at two responsive time windows (CT8  10 and CT22 
      24) through high affinity ML-1 receptors in SCN.

PMID- 11956569
TI  - [Influence of hepatic stimulator substance on p21(ras) expression in human
      hepatic carcinoma cells BEL-7402].
AB  - The hepatic stimulator substance (HSS) was partially purified from schedule
      lighted weanling rat livers. The effects of HSS on p21(ras) expression of human
      hepatic carcinoma cell BEL-7402 were examined. The results showed: (1) HSS was
      capable of promoting the proliferation of the cells, and its molecular weight was
      14 20 kD; (2) the p21(ras) expression was increased under HSS effect time
      dependently, and the effect of HSS appeared synergistic with EGF; (3) the
      p21(ras) expression induced by HSS manifested a dose-dependent manner, and the
      saturation effect of HSS occurred at the concentration of 100 microgram/ml.
      Considering together with our previous report about HSS regulation on EGF
      receptor, these results strongly suggest that the proliferatory effect of HSS on
      hepatic carcinoma cells is presumedly related with EGF receptor-mediated signal
      transduction.

PMID- 11956570
TI  - Pattern adaptation of relay cells in the lateral geniculate nucleus of binocular
      and monocular vision-deprived cats.
AB  - To test whether the pattern adaptation in thalamus is dependent upon postnatal
      visual experience during early life, the responses of relay cells to prolonged
      drifting grating stimulation were recorded extracellularly from the dorsal
      lateral geniculate nucleus (dLGN) of cats reared with binocular and monocular lid
      suture. In binocular vision-deprived cats, 68% of cells recorded showed
      significant adaptation to prolonged grating stimuli within 30 s, with a mean
      response decrease of 33%, and then stabilized gradually. This adaptation was
      stronger than that of relay cells in normal cats. In monocular vision-deprived
      cats, 53% of the cells driven by the deprived eye showed similar adaptation as
      did 44% of the cells driven by the non-deprived eye. These results indicate that
      pattern adaptation could be maintained or even enhanced after visual deprivation
      in early life. It is suggested that pattern adaptation is a general and intrinsic
      property of the dLGN cells, which may be mainly determined by genetic factors.

PMID- 11956571
TI  - [Increased expression of formalin-induced Fos and NADPH-d positive neurons in the
      spinal cord of morphine-tolerant rats].
AB  - Fos immunocytochemistry, NADPH-d histochemistry and Fos/NADPH-d double-labeling
      method were used to study the changes in formalin-induced Fos, NADPH-d positive
      and Fos/NADPH-d double-labeled neurons in the spinal cord of morphine-tolerant
      rats. Formalin-induced Fos-like immunoreactivity (Fos-LI) was located in the
      superficial laminae and neck of ipsilateral spinal cord. Acute administration of
      morphine decreased the expression of Fos-LI in non-tolerant rats, while the
      expression of Fos-LI was significantly increased in morphine-tolerant rats. Fos
      LI was distributed not only in the whole laminae of the ipsilateral spinal cord
      but also in the contralateral spinal cord. Acute administration of morphine was
      ineffective in decreasing the expression of Fos-LI in morphine-tolerant rats.
      Morphine tolerance increased the expression of formalin-induced NADPH-d positive
      neurons in the superficial laminae of spinal dorsal horn. A few formalin-induced
      Fos/NADPH-d double-labeled neurons were detected in the superficial laminae of
      spinal dorsal horn of non-tolerant rats. In morphine-tolerant rats, on the other
      hand, formalin-induced Fos/NADPH-d double-labeled neurons were increased and
      distributed in the whole laminae of the ipsilateral spinal cord and the
      contralateral superficial spinal cord. It is suggested that NO is involved in the
      increase of formalin-induced Fos-LI in the spinal cord of morphine-tolerant rats
      and may play an important role in the development of morphine tolerance.

PMID- 11956572
TI  - [Streptomycin inhibits carotid sinus baroreflex in anesthetized rats].
AB  - The effect of streptomycin on the carotid baroreflex was examined in 23
      anesthetized rats with isolated carotid sinus perfusion. The results obtained are
      as follows. (1) By perfusing the isolated carotid sinus with streptomycin (100
      micromol/L) the functional curve of baroreflex was shifted to the right and
      upward with its peak slope (PS) decreasing from 0.40+/-0.01 to 0.33+/-0.01 kPa
      (P<0.001), and the reflex decrease in the mean arterial pressure (RD) was lowered
      from 6.22+/-0.13 to 5.02+/-0.11 kPa (P<0.001), while the threshold pressure (TP),
      equilibrium pressure (EP) and saturation pressure (SP) were significantly
      increased from 8.27+/-0.25 to 10.33+/-0.32 kPa (P<0.01), 12.71+/-0.21 to 13.33+/
      0.30 kPa (P<0.01) and 24.41+/-0.14 to 26.11+/-0.28 kPa (P<0.01),respectively.
      Among the functional parameters of carotid baroreflex, the changes in RD, PS and
      TP induced by streptomycin were dose-dependent. (2) By perfusing the isolated
      carotid sinus with adenosine (125 micromol/L), carotid baroreflex was
      facilitated. Pretreatment with streptomycin (200 micromol/L) not only eliminated
      the facilitated effect of ado on carotid baroreflex but also caused a reflex
      decrease in MAP to a level lower than control. Taken together, it is suggested
      that streptomycin can markedly inhibit the carotid sinus baroreflex in
      anesthetized rats.

PMID- 11956573
TI  - [Nitric oxide changes aortic function in rats with renal hypertension].
AB  - This work was undertaken to investigate the effect of nitric oxide (NO) on aortic
      function of two-kidney and one-clip (2K1C) rats with renal hypertension. Animals
      were divided into 5 groups: the sham operation, 2K1C, captopril, L-arginine and L
      NAME groups. The results are as follows. At the 4th week after constriction of
      the left renal artery, the mean arterial pressure was significantly elevated. In
      isolated aortic rings, acetylcholine-induced dilation was attenuated, and
      phenylephrine induced contractile response was markedly enhanced. The level of
      aorta cGMP content was significantly lowered. These changes were abolished in
      2K1C rats treated with captopril. L-arginine partially reversed the aortic
      vascular reactivity of 2K1C rats, and elevated aortic cGMP content. In 2K1C rats
      treated with nitric oxide synthase inhibitor, L-NAME, blood pressure was
      increased further, acetylcholine-induced aorta diastolic response was attenuated
      further and cGMP content reduced, while phenylephrine-induced contractile
      response was unaffected. These results suggest that deficiency of nitric oxide
      production and increase in renin-angiotensin system activity may contribute to
      vascular endothelial dysfunction of 2K1C rats, and these factors may be involved
      in development and maintenance of 2K1C renal hypertension.

PMID- 11956574
TI  - Effects of dopamine receptor agonists on the cAMP content in arteries of the
      rabbit.
AB  - Effects of selective dopamine-1 (DA(1)) receptor agonist fenoldopam and dopamine
      2 (DA(2)) receptor agonist propy1-butyl-dopamine (PBDA) on the cAMP generation
      system in renal, pulmonary, mesenteric and femoral arteries of rabbits were
      studied. The results are as follows. (1) Fenoldopam increased the cAMP production
      in a dose-dependent manner in pulmonary, renal and mesenteric arteries. This
      effect of fenoldopam was markedly blocked by specific DA(1) receptor antagonist
      SCH23390, but not at all by specific DA(2) receptor antagonist domperidone. (2)
      PBDA induced a dose-dependent decrease in cAMP content in femoral artery.
      However, the antagonist also moderately increased a dose-dependent cAMP
      production in mesenteric, pulmonary, and renal arteries. (3) Domperidone
      significantly decreased the inhibitory effect of PBDA on cAMP production in
      femoral artery, while it stimulated cAMP production in mesenteric artery but was
      of no effect on that in renal and pulmonary arteries. (4) SCH23390 had no effect
      on the inhibitory action of PBDA in decreasing cAMP content in femoral artery,
      while it markedly decreased the stimulatory action of PBDA on cAMP production in
      renal, pulmonary and mesenteric arteries. These findings suggest the presence of
      DA(1) receptors mediating the cAMP generation system in renal, pulmonary and
      mesenteric arteries, but only DA(2) receptors in femoral artery, and both DA1 and
      DA(2) receptors in mesenteric artery. PBDA inhibits the AC activity via
      stimulation of DA(2) receptors and increases the AC activity via stimulation of
      DA(1) receptors.

PMID- 11956575
TI  - [Comparison of inhibitory effects of three natriuretic peptides on the
      proliferation of pulmonary artery smooth muscle cells of rats].
AB  - The inhibitory effects of atrial natriuretic peptide (ANP), C-type natriuretic
      peptide (CNP) and vasonatrin peptide (VNP) on the proliferation of pulmonary
      artery smooth muscle cells (PASMCs) were compared in rats. Total protein and OD
      value of MTT were detected in cultured rat PASMCs to examine the influence of the
      three peptides on PASMC proliforation induced by phorbol 12-myristate 13-acetate
      (PMA). The results show that PMA (10(  9)  10(  7) mol/L) increased and VNP (10( 
      8)  10(  6) mol/L), ANP and CNP (10(  7)  10(  6) mol/L) decreased the total
      protein and OD value in a dose-dependent manner (P<0.05). The data above suggest
      that PMA stimulates the proliferation of PASMCs while the three peptides inhibit
      the proliferation induced by PMA. Of the three peptides VNP has the strongest
      inhibitory effect.

PMID- 11956576
TI  - [AVP-ergic mechanism in the rostral ventrolateral medulla:a possible role in
      stress-induced hyperviscosity].
AB  - The study was undertaken to find whether microinjection of vasopressin (AVP) into
      the rostral ventrolateral medulla (rVLM) affects blood pressure (BP) and blood
      viscosity in rats and to analyze the effects of AVP-ergic mechanism in the rVLM
      on stress-induced hyperviscosity of rats. The results are as follows. (1)
      Microinjection of AVP into the rostral ventrolateral medulla (rVLM) of normal
      rats resulted in a significant increase in BP and plasma viscosity, which was
      blocked by bilateral microinjection of AVP V(1) receptor antagonist (d(CH2)5 
      Tyr(Me)(2)  AVP) into the same area. (2) The stress-induced pressor response and
      hyperviscosity was abolished by microinjection of AVP V(1) receptor antagonist
      into the rVLM, but not by AVP V(2) receptor antagonist (  adamantaneacetyl(1),O
      Et-D-Tyr(2),Val(4),aminobutyryl(6),Arg(8,9)  -vasopressin). Microinjection of AVP
      V(1) receptor antagonist of the same dosage into bilateral caudal ventrolateral
      medulla (cVLM) or intravenous injection of the antagonist of the same dosage had
      no effect. The above results suggest that the increase of BP and plasma viscosity
      induced by microinjection of AVP into rVLM and the stress-induced pressor
      response and hyperviscosity caused by restraining may be mediated by activation
      of the AVP V(1) receptor in the rVLM.

PMID- 11956577
TI  - A comparison of calcitonin gene-related peptide effects on coronary flow and
      cardiac conduction system in the guinea pig.
AB  - The purpose of this study was to examine the effects of calcitonin gene-related
      peptide (CGRP) on coronary flow and various parts of cardiac conduction system
      (CCS) in the isolated guinea pig heart by recording the cardiac electrogram and
      His bundle activity simultaneously. The coronary flow (CF) was measured and the
      right atrium was paced at incremental frequencies periodically. Perfusing heart
      with CGRP at the concentrations of 3  30 nmol/L increased CF strikingly and dose
      dependently. CGRP (30 nmol/L) caused a moderate and significant increase in the
      spontaneous heart rate, but failed to influence the atrioventricular nodal and
      His bundle-Purkinje fiber conduction time and the longest atrial pacing cycle
      length inducing 3  2 Wenckebach and 2  1 AV nodal conduction. The results
      indicate that CGRP in the guinea pig heart might act mainly on coronary vessels
      and then the sinus node, but did not affect the conductivity and refractoriness
      of the AV conduction system.

PMID- 11956578
TI  - Melatonin attenuates the intensity of beta-endorphin immunoreactivity in the
      arcuate nucleus of rat hypothalamus.
AB  - The present study was undertaken to observe the effect of exogenously
      administered melatonin on the intensity of beta-endorphin (beta-Ep)
      immunoreactivity of the neuron in the arcuate nucleus of rat hypothalamus with an
      aim to explore the possible mechanisms of the analgesic effect of melatonin. The
      experimental rats were divided into two groups, one injected intraperitoneally
      with melatonin (110 mg/kg) and the other with only a vehicle. One hour after
      injection, the brain was processed for coronal sections, which were stained with
      immunohistochemical ABC technique. The integral optical density (IOD) and mean
      optical density (OD) of the stained sections were measured with a computer
      assisted image-processing and analytical system. beta-Ep immunoreactivity was
      much decreased in the sections treated with melatonin and the IOD and OD were
      also decreased significantly (P<0.01; P<0.05). The above results suggest that
      melatonin may result in a decrease of beta-Ep content in the arcuate nucleus, as
      a result of increased beta-Ep release induced by administration of melatonin. It
      is likely that the analgesic effect of melatonin may be in part mediated by the
      release of beta-endorphin from the arcuate nucleus.

PMID- 11956579
TI  - NO-releasing NSAIDs and colon cancer chemoprevention: a promising novel approach
      (Review).
AB  - The chemoprevention of colon cancer, the second leading cause of cancer-related
      deaths in the United States, has been pursued actively during the last two
      decades. Methodological problems and those stemming from the available agents per
      se have constrained this difficult task; to some extent, these problems persist
      to date. That NSAIDs decrease the incidence of and mortality from colon cancer
      has been a major advance in chemoprevention. These compounds are, however,
      limited by their significant side effects. NO-releasing NSAIDs (NO-NSAIDs) are a
      novel class of compounds, synthesized to overcome the limitations of NSAIDs. In
      general, they appear safer and much more effective than their traditional
      counterparts. We review their structural features, metabolism and pharmacological
      actions. In vitro and in vivo studies indicate that they are much more effective
      than traditional NSAIDs in modulating colonocyte kinetics and the formation of
      premalignant colon lesions. Their mechanism of action is complex and not fully
      understood, including modulation of NO synthesis, signaling mediated via NF
      kappaB and likely other pathways. Current early findings indicate that NO-NSAIDs
      may play a highly promising role in the chemoprevention of colon cancer.

PMID- 11956580
TI  - Combined effects of onconase and IFN-beta on proliferation, macromolecular
      syntheses and expression of STAT-1 in JCA-1 cancer cells.
AB  - Prostate cancer (CaP), the most common malignancy in American men, presents its
      greatest challenge to clinicians when the cancer progresses to the hormone
      refractory state. In the present investigation, we studied the combined effects
      of interferon (IFN) and onconase, each of which has reported antitumor activity,
      on growth and specific protein expression in JCA-1 cells. Cells were treated for
      up to 3 days with 1 and 5 microg/ml onconase, with and without concurrent
      addition of IFN-beta(ser) (10(3) IU/ml). Cell count and viability, and de novo
      RNA and protein synthesis were determined. Expression and subcellular
      distribution of STAT-1 were also assessed by immunoblot analysis. JCA-1 cells
      treated for 3 days with IFN or onconase showed a 15-30% reduction in cell
      proliferation, which was increased to 42-51% with both agents. Analysis of
      [35S]methionine incorporation into cells confirmed a more pronounced inhibitory
      effect elicited by IFN-beta and onconase; IFN-beta and 1 microg/ml onconase each
      decreased de novo protein synthesis by 23-25%, while the combination resulted in
      59% suppression. Similar studies using incorporation of [3H]uridine into RNA
      yielded less significant effects. Further investigation using pre-labeled
      cellular RNA and proteins showed that either agent or their combination did not
      affect the turnover of macromolecules. To test whether the antiproliferative
      effects of IFN-beta and onconase were correlated with one or more specific gene
      changes, expression of an IFN-modulated protein, STAT-1, was determined. Both
      phosphorylated and unphosphorylated forms of STAT-1 and its subcellular
      distribution in the nucleus and cytoplasm, were increased 3-fold by IFN-beta. The
      IFN-elicited elevation of STAT-1 was not additionally augmented by onconase but
      was reduced 20-25% when onconase was simultaneously present as IFN-beta. These
      data show that the overall changes in STAT-1 did not correlate with the reduction
      in cell growth and the suppression of de novo protein/RNA synthesis elicited by
      these two agents, and imply that other target proteins are likely to be involved
      in the combined effects of IFN-beta and onconase in JCA-1 cells.

PMID- 11956581
TI  - Expression of retinoid-related genes in serum-free cultures of normal,
      immortalized and malignant human oral keratinocytes.
AB  - Retinoids are used in the clinical treatment of oral squamous carcinoma,
      including both early and late stages. Inter-individual variation in
      responsiveness, including a common insensitivity of advanced stages, suggest that
      changes in retinoid-related functions might characterize tumor development. To
      investigate a genetic basis for this hypothesis, an in vitro multi-step model of
      carcinogenesis involving normal (NOK), SV40 T antigen-immortalized (SVpgC2a) and
      malignant (SqCC/Y1) oral keratinocytes was analysed under identical culture
      conditions using micro-array technique (Affymetrix HG_U95A chip) for expression
      of 52 genes related to retinoid metabolism and actions. The variable detection of
      between 22-26 transcripts in the cell lines, involving binding/transport factors,
      receptors, transcriptional activators/repressors and responsive genes, indicated
      specificity in regards to the expression of known retinoid-related genes in oral
      keratinocytes. The transformed cell lines variably exhibited differences as
      compared to NOK, i.e., lower transcript levels for cellular retinol binding
      protein, the cellular retinoic acid binding protein II (CRABP II) and retinoic
      acid receptor gamma, whereas in contrast, the levels of CRABP I were higher.
      Transcripts for proteins interacting with nuclear retinoid receptors were
      similarly expressed among the cell types, whereas transcripts for retinoid
      metabolizing enzymes were generally not detected. Finally, transcripts of
      retinoid-responsive genes, including RARRES3, RI58, NN8-4AG and midkine, were
      variably expressed. The overall results imply selective expression of retinoid
      related functions in normal and transformed keratinocytes, and that cell
      transformation can impair the capacity for binding and storage of retinol as well
      as retinoic acid-mediated signalling. These multiple alterations are consistent
      with possible retinoid insensitivity during oral carcinogenesis.

PMID- 11956583
TI  - Human breast cancer MCF-7 cell line contains inherently drug-resistant subclones
      with distinct genotypic and phenotypic features.
AB  - The resistance of cancer cells to multiple chemotherapeutic agents poses a major
      problem in the successful treatment of breast cancer. Whether drug resistance is
      due to changes induced in the drug-exposed tumor cells or represents the
      selective growth of one or more drug-resistant clones present in the initial
      tumor remains controversial. Here we provide evidence that the development of
      multidrug resistance in a human breast cancer cell line (MCF-7) is a result of
      propagation of an inherently resistant subclone. The drug-resistant MCF-7 (MCF
      7/DOX) cells exhibited several phenotypic and genotypic features that were
      notably distinct from those observed in the parental drug-sensitive (MCF-7/WT)
      cells. The most striking change was the presence of a full-length functional
      caspase-3 in MCF-7/DOX cells that was missing in the parental MCF-7/WT cells due
      to a deletion mutation in the caspase-3 gene. A drug-resistant MCF-7 cell subline
      (MCF-7/WT/DOX) was established by exposing the MCF-7/WT cells directly to a high
      dose of doxorubicin and used for determining the phenotypic and genotypic
      alterations associated with drug resistance. The MCF-7/WT/DOX cells exhibited
      alterations identical to those of the MCF-7/DOX cells but which were strikingly
      distinct from the parental MCF-7/WT cell line. These results suggest that drug
      resistance is an inherent property of some cancer cells that are present in the
      initial tumor burden and exhibit distinct phenotypic/genotypic alterations.

PMID- 11956582
TI  - No evidence for involvement of beta-catenin and APC in urothelial carcinomas.
AB  - The wnt pathway plays an important role in embryonal patterning and cell fate
      determination, involving stabilization of nuclear and cytoplasmic beta-catenin
      (CTNNB1) mediated by APC, axin, and other proteins. Uncomplexed beta-catenin
      binds to TCF/LEF transcription factors and activates the expression of growth
      regulatory target genes such as c-myc or cyclin D1. In colorectal and other
      cancers, constitutive wnt signaling results frequently from mutations in one or
      more pathway components, e.g. APC and beta-catenin, resulting in nuclear and/or
      cytoplasmic accumulation of beta-catenin. In the present study, the most frequent
      alterations in the CTNNB1 and APC genes were investigated in primary urothelial
      bladder tumors and cell lines. Snap-frozen bladder tumors (n=99) of different
      stages and grades and 4 cell lines (RT4, RT112, J82, UROtsa) were investigated
      for APC allelic deletions by loss of heterozygosity (LOH) analysis. The most
      frequent mutated regions of CTNNB1 (degradation box in the third exon) and APC
      (mutation cluster region) were directly sequenced. Beta-catenin expression was
      analyzed by immunofluorescence in the cell lines. LOH at the APC gene locus on
      chromosome 5q21 was found in 7 of 72 (10%) of the informative cases. No mutations
      were found in either CTNNB1 or APC. A previously described polymorphism at codon
      1493 of the APC gene was detected in 8 tumors and 3 cell lines. All cell lines
      showed normal membranous beta-catenin staining without evidence for nuclear or
      cytoplasmic accumulation. Alteration of APC and beta-catenin, which are the most
      frequent wnt pathway alterations in many tumor types, are rare events in
      urothelial carcinomas. Other wnt pathway members, such as axin, may play an
      important role in urothelial carcinogenesis.

PMID- 11956584
TI  - The role of thrombin in the neo-vascularization of malignant gliomas: an
      intrinsic modulator for the up-regulation of vascular endothelial growth factor.
AB  - Thrombin is a key enzyme in the blood coagulation system where it converts
      fibrinogen to fibrin. It participates in a variety of biological processes such
      as the induction of mitogenesis and of morphological changes, the production of
      cytokines and growth factors, and apoptosis. To clarify the role of thrombin in
      the proliferation of human malignant gliomas, we investigated its effect on the
      expression of vascular endothelial growth factor (VEGF) in vitro and determined
      its intrinsic expression in human glioma tissues. In 3 human glioma cell lines
      tested, U-87 MG, U-251 MG, and U-105 MG, thrombin induced the VEGF mRNA
      expression and protein in a dose- and time-dependent manner. The thrombin
      receptor expression was detectable by RT-PCR and immunoblot. The secretion of
      VEGF protein in glioma cells was stimulated by the thrombin receptor agonist
      peptide and the induction of VEGF was significantly blocked by the thrombin
      inhibitor hirudin, indicating that the up-regulation of VEGF was mediated by the
      thrombin/thrombin receptor pathway. Immunoblot analysis demonstrated that
      prothrombin, the precursor of thrombin, was distributed in all 10 glioma tissues
      examined. In situ hybridization and immunohistochemical analysis revealed the co
      localization of prothrombin mRNA-positive and GFAP-positive cells in the glioma
      tissues. Although various factors may be involved in the up-regulation of VEGF,
      our results suggest that human gliomas per se express prothrombin, and that
      thrombin, converted from prothrombin in glioma tissues, substantially stimulates
      angiogenesis in an autocrine fashion.

PMID- 11956585
TI  - Anticancer cytotoxicity and nephrotoxicity of the new platinum (II) complexes
      containing diaminocyclohexane and glycolic acid.
AB  - Cisplatin is an important antineoplastic agent, but dose-limiting nephrotoxicity
      prevents potential efficacy. There is interest in developing new platinum agents
      that have less toxicity. We have synthesized novel platinum (II) coordination
      complexes containing diaminocyclohexane as carrier ligands, and glycolic acid as
      a leaving group. In this study, new platinum (II) complex compounds were
      evaluated for cytotoxicity on cancer cell lines and nephrotoxicity. The new
      platinum complexes have demonstrated high efficacy in the cytotoxicity against
      human ovarian adenocarcinoma cell lines (SKOV-3/NIH.OVCAR-3) and human prostate
      carcinoma cell lines (DU-145/PC-3). The cytotoxicity of these compounds against
      rabbit proximal renal tubular cells and human renal cortical tissues was
      determined by MTT assay, the [3H]-thymidine uptake and glucose consumption test,
      and found to be considerably less than those of cisplatin. Based on our results,
      these novel platinum compounds appear to be valuable lead compounds with high
      efficacy and low nephrotoxicity.

PMID- 11956586
TI  - Prognostic significance of S100A4 expression in gallbladder cancer.
AB  - The calcium-binding protein S100A4 has been characterized as a metastasis
      inducing molecule, and regulates cell motility and invasiveness of cancer cells.
      In order to clarify the significance of the expression of S100A4 as a prognostic
      factor in gallbladder cancer, S100A4 expression in resected gallbladder cancers
      were examined using an immunohistochemical staining technique. The relationship
      between S100A4 expression and clinicopathological factors including prognosis
      were evaluated. Twenty-five of 60 cases (42%) demonstrated positive staining for
      S100A4. There was no statistically significant association between S100A4 and
      histological grade, T, N, M factor, presence of stone, or stage. Kaplan-Meier
      method showed the 5-year survival rate of the group staining positive for S100A4
      (31.5%) to be statistically poorer than that of the group staining negative for
      S100A4 (78.2%). Also in T2 cases, the 5-year survival rate of the group staining
      positive for S100A4 (57.1%) was statistically poorer than that of the group
      staining negative for S100A4 (83.3%). On univariate analysis, positive staining
      for S100A4 was a significant prognostic factor, and the hazard ratio was 4.05. On
      multivariate analysis, positive staining for S100A4 is also a significant
      predictor of prognosis second to T factor. These results indicate that positive
      staining for S100A4 is useful in assessing the prognosis of patients with
      gallbladder cancer as well as TNM factors.

PMID- 11956587
TI  - Expression and accumulation of lumican protein in uterine cervical cancer cells
      at the periphery of cancer nests.
AB  - Lumican is a member of a small leucine-rich proteoglycan (SLRP) family and is
      reported to be overexpressed during the wound healing process of the cornea, and
      ischemic and reperfused heart. In the carcinomatous tissues, lumican is
      overexpressed in human breast and pancreatic cancer tissues. In the present
      study, we aimed to clarify the expression of lumican mRNA and its protein in
      human cervical cancer cell lines (CaSki, ME-180 and HeLa cells) and their
      localization in normal and cancerous human cervical tissues. Reverse
      transcription-polymerase chain reaction and Western blot analysis revealed the
      expression of lumican mRNA and its protein in CaSki, ME-180 and HeLa cells. No or
      weak immunoreactivity of the lumican protein was observed in stroma but not in
      squamous and ductal cells of non-cancerous uterine cervical tissues. In 21 of 28
      (75%) cervical cancer cases, the lumican protein was strongly expressed in cancer
      cells, and accumulated particularly in cancer cells at the periphery of the
      cancer nests. It was also expressed in the fibroblasts adjacent to the cancer
      cells. In situ hybridization analysis revealed that lumican mRNA was not
      expressed in squamous or ductal epithelial cells in non-cancerous tissues, but
      was expressed in most cancer cells and stromal fibroblasts in uterine cervical
      cancer tissues. The lumican protein was not localized in normal squamous or
      ductal cells close to cancer cells, but its mRNA was strongly expressed in the
      same cells. To our knowledge, this is the first report on lumican synthesized by
      squamous cell carcinomas. These findings may indicate that the accumulated
      lumican protein in cancer cells at the periphery of cancer nests may play roles
      in the growth or invasion of human cervical cancer cells.

PMID- 11956588
TI  - Doxorubicin enhances TRAIL-induced apoptosis in prostate cancer.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis
      in various tumor cells. The anthracycline doxorubicin (DOX) can sensitize several
      types of cancer cells to TRAIL-mediated apoptosis. Here we report that DOX
      enhances TRAIL-induced apoptosis and cytotoxicity against prostate cancer cells.
      Cytotoxicity was determined by a MTT assay. Synergistic effect was assessed by
      isobolographic analysis. Caspase activity was determined by a quantitative
      colorimetric assay. The combination treatment with DOX and TRAIL resulted in a
      synergistic cytotoxic effect on LNCaP, LNCaP-Bcl-2, PC-3, and PC93 human prostate
      cancer cell lines, but not on normal human prostatic stromal cells. Synergistic
      cytotoxicity was also obtained even when the exposure time was shortened from 24
      to 8 or 2 h. A similar effect was achieved with TRAIL in combination with
      epirubicin, pirarubicin, or amrubicin. The synergy obtained in cytotoxicity with
      TRAIL and DOX was also achieved in apoptosis. DOX treatment significantly
      activated caspase-8, -6, and -3 in LNCaP cells. Furthermore, the synergistic
      cytotoxicity of TRAIL and DOX was completely inhibited by Z-VAD-FMK, and partly
      inhibited by Ac-IETD-CHO, Ac-DQTD-CHO, or Ac-DMQD-CHO. These findings indicate
      that DOX enhances TRAIL-induced apoptosis and cytotoxicity in prostate cancer by
      activation of caspase cascades, and suggest that TRAIL in combination with DOX
      have a therapeutic potential in the treatment of prostate cancer.

PMID- 11956589
TI  - Effect of hypoxia on human seminoma cells.
AB  - Since hypoxia has been considered to enhance metastatic potential in solid tumors
      via a neo-angiogenesis caused by vascular endothelial cell growth factors (VEGFs)
      induced by hypoxia inducible factor-1alpha (HIF-1alpha), the effects of hypoxia
      on human seminoma cell lines were examined in terms of growth, morphology, gene
      expression, protein expression and cell cycle perturbation. Growth was inhibited
      in long-term cultures with morphological changes to the spindle form. The gene
      expression of VEGF-C was markedly enhanced and the production of VEGF-A increased
      during hypoxia, although HIF-1alpha was not upregulated at the protein or message
      level. Hypoxic culture caused G1 cell cycle arrest with upregulation of the
      p15/ink4b and p27/Kip1 genes, whereas no increase of apoptotic cells was observed
      on up-regulation of the heat shock protein (HSP) 70 gene. The adhesion molecules
      were only slightly altered.

PMID- 11956590
TI  - Characterization of 2 novel and 2 recurring BRCA1 germline mutations in breast
      and/or ovarian carcinoma patients from the area of Naples.
AB  - We have analyzed 18 families with high incidence of breast cancer or breast and
      ovarian cancer for the presence of BRCA1 mutations. We identified 4 mutations in
      the BRCA1 gene in 4 unrelated probands who belong to families with at least 1
      case of breast and 1 case of ovarian cancer. Two of the mutations reported in
      this study are novel (GAA(1172)-->TAA in family Naples 14, GAA(1765)-->TAA in
      family Naples 20) whereas the others are already present in the Breast Cancer
      Information Core Electronic Database (http://nchgr.nih.gov/ Intramural
      research/Lab transfer/Bic/) (5382insC in family Naples 18 and 2080delA in family
      Naples 19). Conversely, no mutation in the BRCA1 gene was detected in 14 families
      characterized by 2 or more cases of breast cancer only, even if bilateral and
      with early-onset. These results indicate that germline mutations in the BRCA1
      gene highly predispose for a cancer syndrome that involves the presence of both
      breast and ovarian cancer.

PMID- 11956591
TI  - Cytogenetic and molecular analyses of multiple endocrine neoplasias of the MEN1
      syndrome.
AB  - A pancreas carcinoid, an adrenocortical adenoma, three parathyroid adenomas and a
      parathyroid hyperplasia of 5 MEN1 patients were used for loss of heterozygosity
      (LOH) and comparative genomic hybridization (CGH) studies. The MEN1 gene is
      located in the region 11q13, approximately 30 kb distal to PGYM. Four tumors
      showed LOH on chromosome 11q13 (D11S11335, PGYM, D11S1883, FGF3, D11S937) however
      LOH was also found beyond 11q13. The pancreas carcinoid and adrenocortical
      adenoma, both from the same patient, showed LOH at marker 11q23.3 and 11q25. In
      the three parathyroid adenomas LOH was detected in five different markers: 11q21,
      11q22.3, 11q23.2, 11q23.3 and 11q25. No LOH was found in parathyroid hyperplasia.
      CGH analysis showed in case of the pancreas carcinoid losses on chromosomes 1p,
      2q, 3, 6, 9p, 11 and 12p. Gains were found at 4, 5, 7, 8, 13, 14, 15q, 18, 19.
      The parathyroid adenoma of the third patient showed losses only on chromosome 11
      in the region 11p12-p15 and 11q12-q23. Our data indicate that other genes are
      involved in the tumorigenesis of the MEN1 syndrome. Especially the numerous
      allelic losses between markers 11q23 and 11q25 (D11S938 and D11S910) are a hint
      for further tumor suppressor genes on chromosome 11.

PMID- 11956592
TI  - Molecular cloning and characterization of WRCH2 on human chromosome 15q15.
AB  - WNT signals are transduced to the JNK pathway, the Ca2+-releasing pathway, or the
      beta-catenin - TCF pathway through seven-transmembrane-type WNT receptors encoded
      by Frizzled genes (FZD1-FZD10). WRCH1/ARHV and CDC42 are potentially implicated
      in the WNT-JNK pathway. Here, WRCH2/ARHV cDNAs were isolated by using
      bioinformatics and cDNA-PCR. WRCH2 gene, consisting of at least 3 exons, encoded
      a 236-amino-acid protein with proline-rich domain and GTPase domain. WRCH2 was
      homologous to WRCH1 (55.4% total-amino-acid identity) and CDC42 (43.5% total
      amino-acid identity). WRCH2 gene was located on human chromosome 15q15, which is
      one of fragile sites in the human genome. A single nucleotide substitution (632
      Gright curved arrow A) was identified between WRCH2 cDNA and human genome draft
      sequences, which resulted in Arg177Lys amino-acid substitution. WRCH2 mRNA was
      relatively highly expressed in pancreas, placenta, and fetal brain. WRCH2 mRNA
      was over-expressed in TMK1 (gastric cancer), Hs700T (pancreatic cancer), HeLa S3
      (cervical cancer), and A549 (lung cancer). WRCH2 mRNA was moderately expressed in
      MKN74, MKN45, MKN28, KATO-III (gastric cancer), HL-60 (pro-myelocytic leukemia),
      Raji (Burkitt's lymphoma), and SW480 (colorectal cancer). WRCH2 mRNA was up
      regulated in 3 out of 8 cases of primary gastric cancer. Because Wrch1 can
      activate PAK1 and JNK1, and induce filopodium formation and stress fiber
      dissolution, over-expression of WRCH2 mRNA in human cancer cells might also lead
      to more malignant phenotype.

PMID- 11956593
TI  - A rapid screening assay for antioxidant potential of natural and synthetic agents
      in vitro.
AB  - There are literally thousands of known agents with potential chemopreventive and
      antioxidant activity; however, the expanding list of natural and synthetic
      compounds makes it difficult to test every agent in the widely accepted 2-year
      animal bioassay and human clinical trials. Therefore, short-term screening assays
      are needed to sort out the most efficacious compounds for long-term animal
      studies. In the present study, the identification of chemopreventive agents with
      efficacious antioxidant potential was explored with a Cu2+-mediated Fenton-type
      reaction, coupled with oxidative DNA lesion detection by 32P-postlabeling.
      Several agents inhibited the formation of 8-oxo-2'-deoxyguanosine (8-oxodG), a
      benchmark oxidative DNA lesion, but ellagic acid, a polyphenol found in berries,
      offered maximal (>80%) inhibition of 8-oxodG formation. However, a well-known tea
      polyphenol, epigallocatechin gallate, along with silymarin and D,L-sulforaphane,
      exhibited a pro-oxidant effect, with 50-70% increase in 8-oxodG induction. In
      general, our results agree with the reported antioxidant - pro-oxidant activities
      of the compounds, rendering this in vitro screening assay to be useful in
      determining the antioxidant potential of compounds rapidly and cost-effectively.

PMID- 11956594
TI  - Evidence for hormone-responsive cleavage of gonadotropin-releasing hormone by the
      plasma membrane of ovarian cancer cells.
AB  - Gonadotropin-releasing hormone (GnRH) produced by ovarian cancer cells acts as a
      negative autocrine regulator in the ovarian cancer cell proliferation. GnRH and
      its analogs retard the proliferation of ovarian cancers bearing GnRH receptor,
      and thus the GnRH hydrolysis may be responsible for their growth. We determined
      the principal mechanism of GnRH hydrolysis by ovarian cancer cells and its
      coupling to GnRH receptor. GnRH cleaving activity was assessed by measuring the
      degradation of exogenous [3H]GnRH labeled at the N-terminal residue and the
      appearance of labeled degradation product. Approximately 98% of GnRH hydrolysis
      by plasma membrane from ovarian cancers surgically removed was accounted for by
      the cleavage at Tyr5-Gly6 to yield (1-5)GnRH. The GnRH degrading activity in the
      plasma membrane was approximately 6-fold higher than those in homogenate
      fraction. The membrane GnRH cleaving activity was metal ion-independent and
      sensitive to inhibition by N-ethymaleimide and endopeptidase inhibitors;
      characteristics suggestive of membrane-bound endopeptidase activity. No effects
      of buserelin and leuprolide on the [3H]GnRH hydrolysis at 4-fold higher
      concentration of the [3H]GnRH substrate suggested great resistance of the GnRH
      analogs toward the endopeptidase. GnRH degrading activity increased by 1.5-fold
      when the ovarian cancer Caov-3 cells were exposed to buserelin in intact cells
      prior to assay of cell membranes. These data demonstrate that GnRH is hydrolysed
      in the plasma membrane of ovarian cancer cells by the action of endopeptidase and
      provide the initial evidence for the functional coupling of the GnRH degradation
      to GnRH receptor activation.

PMID- 11956595
TI  - Molecular cloning and characterization of Strabismus 2 (STB2).
AB  - WNT signaling pathway is implicated in carcinogenesis and embryogenesis. WNT
      signal is transduced to the beta-catenin - TCF pathway, the JNK pathway, or the
      Ca2+-releasing pathway through seven-transmembrane-type WNT receptors encoded by
      Frizzled (FZD) genes. Xenopus Strabismus (Stbm) is a tetra-spanning transmembrane
      protein interacting with Dishevelled, and is a negative regulator of the WNT -
      beta-catenin - TCF signaling pathway. STB1/KIAA1215/VANGL2 is a human orthologue
      of Xenopus Stbm (90.6% total-amino-acid identity). Here, STB2/VANGL1 gene
      fragments were identified in human genome draft sequences by using
      bioinformatics, and STB2 cDNAs were isolated by using cDNA-PCR. STB2 gene
      consisted of at lest 7 exons, and encoded a 524-amino-acid protein with 4
      transmembrane domains and the C-terminal Ser/Thr-X-Val motif. Human STB2 was
      homologous to human STB1 (73.1% total-amino-acid identity) and Xenopus Stbm
      (72.7% total-amino-acid identity). STB2 gene was clustered with Calsequestrin 2
      (CASQ2) gene in tail-to-tail manner (interval less than 5.0 kb), and CASQ2 gene
      is mapped to human chromosome 1p11-p13.3 or linked to human chromosome 1p13-p21.
      STB2 mRNAs of 4.8- and 6.8-kb in size were expressed almost ubiquitously in
      various normal tissues. STB2 mRNA was significantly up-regulated in gastric
      cancer cell lines MKN28, MKN74, pancreatic cancer cell lines BxPC-3, PSN-1 and
      Hs766T. On the other hand, STB2 mRNA was significantly down-regulated in a
      pancreatic cancer cell line AsPC-1. This is the first report on molecular cloning
      and characterization of STB2.

PMID- 11956596
TI  - Expression and regulation of WNT8A and WNT8B mRNAs in human tumor cell lines: up
      regulation of WNT8B mRNA by beta-estradiol in MCF-7 cells, and down-regulation of
      WNT8A and WNT8B mRNAs by retinoic acid in NT2 cells.
AB  - Xenopus wnt-8 (Xwnt-8) is one of the most potent Wnts to activate the WNT - beta
      catenin - TCF signaling pathway. We have previously cloned and characterized
      WNT8A and WNT8B, two human homologues of Xwnt-8. Here, we investigated expression
      and regulation of WNT8A and WNT8B mRNAs in human tumor cell lines by using cDNA
      PCR. WNT8A mRNA was undetectable in 7 pancreatic cancer cell lines, but WNT8B
      mRNA was detected in pancreatic cancer cell lines PSN-1, BxPC-3, MIA PaCa-2. Both
      WNT8A and WNT8B mRNAs were undetectable in 7 brain tumor cell lines. Although
      WNT8A mRNA was undetectable in 3 breast cancer cell lines, WNT8B mRNA was
      detected in the breast cancer cell line MCF-7. WNT8B mRNA, but not WNT8A mRNA,
      was significantly up-regulated by beta-estradiol in MCF-7 cells. WNT8A mRNA was
      detected in embryonal tumor cell lines NEC-14, NCC-IT, and NT2, while WNT8B mRNA
      was detected in embryonal tumor cell lines NEC-8, NEC-14, and NT2. Because NT2
      cells differentiate into neuronal cells after all-trans retinoic-acid treatment,
      effects of all-trans retinoic acid on mRNA expression of WNT8A and WNT8B were
      next investigated. WNT8A and WNT8B mRNAs were down-regulated together in NT2
      cells after all-trans retinoic-acid treatment. WNT8A and WNT8B might play key
      roles in embryonal tumors and embryonic stem cells through synergistic activation
      of the beta-catenin - TCF signaling pathway.

PMID- 11956597
TI  - UDP-GlcNAc2-epimerase regulates cell surface sialylation and cell adhesion to
      extracellular matrix in Burkitt's lymphoma.
AB  - Alteration of cell surface glycoconjugates plays a crucial role in many
      biological phenomenon, including invasion and metastasis. In the present study,
      we investigated the relationship between cell surface sialylation and the
      adhesive properties of two clones (3G3 and 3D2) of a human Burkitt's lymphoma
      cell line, HBL-8 to extracellular matrix. By flow cytometric analysis we found
      that the cell surface of 3G3 clone was highly sialylated and that of the 3D2
      clone were hyposialylated. Moreover, cell surface sialic acid content was
      significantly greater in the 3G3 clone than in the 3D2 clone. In vitro adhesion
      assays showed that cell surface sialylation in the 3G3 clone cells might reduce
      their attachment to collagen type IV and fibronectin, compared to 3D2 clone.
      Sialic acid metabolic complementation assays using several precursors of sialic
      acid suggested that hyposialylation in the 3D2 clone resulted from low activities
      of uridine diphosphate-N-acetylglucosamine-2-epimerase (UDP-GlcNAc2-epimerase)
      which is a key enzyme in sialic acid biosynthesis. From RT-PCR analysis the
      expression of UDP-GlcNAc2-epimerase mRNA was found to be correlated with sialic
      acid content in the two clones of HBL-8. Therefore, expression of UDP-GlcNAc2
      epimerase mRNA may regulate the expression of sialoglycoconjugates which affect
      the adhesion of lymphoma cells to collagen type IV and fibronectin.

PMID- 11956598
TI  - Prediction of postoperative survival by preoperative serum concentrations of anti
      p53 compared to CEA, CA 50, CA 242 and conventional blood tests in patients with
      colorectal carcinoma.
AB  - Blood samples were obtained preoperatively from 151 consecutive patients who were
      operated for colorectal carcinoma; of these 132 patients underwent curatively
      aimed operations. Patients who lived for more than five years without any
      evidence of relapse were classified as survivors and those who died during follow
      up were classified as non-survivors. Tumors were staged according to Dukes and
      tumor differentiation was classified as high, intermediate or low. Serum anti-p53
      was determined in all patients and compared to CEA, CA 50 and CA 242 in serum as
      well as to blood hemoglobin concentration (Hb), erythrocyte sedimentation rate
      (ESR), serum alkaline phosphatases (ALP), in the same preoperative blood samples
      for comparison of power to predict mortality in colorectal cancer. Tumor
      differentiation and Dukes classification predicted survival and the risk to die
      of colorectal carcinoma as expected. CA 242 and anti-p53 titers in serum were not
      significantly different among groups of patients with Dukes A-D tumors, while Hb,
      ESR, ALP, CEA and CA 50 were significantly different with increasing levels
      appearing in Dukes C-D, except for Hb which decreased. Survivors had lower ESR,
      ALP, CEA, CA 50 and CA 242, while Hb and serum anti-p53 titers were not different
      among survivors and non-survivors. Survivors among Dukes A-C patients had normal
      Hb, ESR, ALP and CA 242 before operation, while non-survivors had increased ESR,
      CEA and CA 50. Levels of anti-p53 were unrelated to concentrations of all other
      blood and serum variables, and did not predict survival in Dukes A-D patients.
      Serum levels of CEA and CA 50 displayed a significantly altered distribution
      among survivors and non-survivors (p<0.01). This altered distribution was
      independent of Dukes A-C tumor stage for CEA (p<0.05) but not for CA 50. Based on
      these results, we conclude that patients with CEA levels above 15 ng/ml should be
      regarded as high risk patients even when their tumors are classified as Dukes B.
      These patients may benefit from neoadjuvant or adjuvant chemotherapy.

PMID- 11956599
TI  - Occurrence of tumor antigen pRL1a specific CD8 T cells in spleen cells from
      syngeneic BALB/c, semiallogeneic (BALB/c x C57BL/6)F1 and allogeneic C57BL/6
      mice.
AB  - We investigated the generation of CD8 cytotoxic T-lymphocytes (CTL) that
      recognized a dominant pRL1a peptide bound to H-2L(d) molecule on RL male 1
      leukemia in spleen cells from RL male 1-bearing syngeneic BALB/c, semiallogeneic
      CB6F1 and allogeneic B6 mice by repetitive in vitro stimulation with RL male 1
      tumor. CD8 T cells in cultures were also analyzed by H-2L(d)/pRL1a tetramer
      staining. We showed that pRL1a-specific CTL were more efficiently generated in
      spleen cells from RL male 1-bearing high responder CB6F1 mice than in low
      responder BALB/c mice, and this correlated well with the occurrence of H
      2L(d)/pRL1a tetramer binding CD8 T cells. Furthermore, we showed that in spleen
      cells from RL male 1-bearing allogeneic B6 mice, H-2L(d)/pRL1a complex specific
      CD8 T cells were present at a significant frequency. H-2L(d)/pRL1a recognizing B6
      CTL but not BALB/c or CB6F1 CTL gradually lost CD8 expression on their surface by
      multiplication of in vitro stimulation.

PMID- 11956600
TI  - A summary of two clinical studies on tumor cell dissemination in primary and
      metastatic breast cancer: methods, prognostic significance and implication for
      alternative treatment protocols (Review).
AB  - Although only less than 10% of women with primary breast cancer have
      clinicopathologic signs of overt metastases, metastatic relapse occurs in about
      half of the cases with apparently localized tumors within five years after
      surgery. In 23% of the patients, bone marrow metastases are detectable at first
      relapse and this rate even increases in patients with metastatic breast cancer.
      However, hematogeneous or lymphatic spread of occult tumor cells can arise before
      diagnosis at an early stage of primary tumor growth and is regularly
      underestimated by currently available clinical and pathologic staging procedures.
      We studied cytokeratin-positive (CK+) cells in the bone marrow (BM) and tumor
      markers in the blood of 128 patients with primary breast cancer in order to
      obtain an early diagnosis of residual disease. In a second study, we monitored
      cytokeratin (CK)/17-1A positive cells in the BM and peripheral blood stem cells
      (PBSC) to evaluate whether dose intensive or high-dose (HD)-chemotherapy can
      eliminate micrometastases in high-risk breast cancer patients. The overall CK+
      rate was 34% (44/128 patients), 29% (15/51) for patients with T1 tumors, 33%
      (28/84) for N0 patients and 31% (26/82) for patients with G1-2 breast carcinoma.
      Interestingly, 67% of CK+ patients were only positive in one of the two BM
      aspirates studied. At least one tumor marker including carcinoembryonic antigen,
      carbohydrate antigen 15-3 and tissue polypeptide antigen, was increased in 58/128
      (45%) patients [21/58 (36%) were CK+ in the BM]. Surprisingly, levels for the
      extracellular domain of Her-2/neu in serum samples were within the normal range
      in every patient studied. After a 2-year follow-up, 7/128 patients relapsed (3/7
      CK+/TM-; 2/7 CK-/TM+; 2/7 CK-/TM-). We concluded that studying two BM aspirates
      for CK+ cells by immunocytochemistry in combination with tumor marker
      determination is useful for identifying patients with a higher risk for relapse.
      A tumor cell enrichment technique, applied in 70 patients prior to
      immunocytochemistry using dynabeads directly coupled to an antibody (BerEp4)
      targeting the 17-1A antigen, did not enhance the detection rate of disseminated
      tumor cells in this patient group. We monitored CK+/17-1A+ cells in the BM and
      PBSC and studied Her-2/neu serum levels of patients with locally advanced (n=13,
      group 1) and metastatic breast cancer (n=30, group 2). CK+ cells were found in
      the BM of 3/13 (23%) group 1 patients before but not after chemotherapy resulting
      in an overall survival (OS) of 92% after a median follow-up of 33 months.
      Contamination of PBSC in 2/9 (22%) patients was not associated with decreased
      survival. In group 2 patients, the CK+ rate was 60% (18/30 patients) before and
      40% (4/10 patients) after therapy with an OS rate of 43% after 29 months. PBSC
      samples were positive in 7/24 (29%) patients. CK+ BM and PBSC led to a rapid
      progress and short OS whereas tumor cell free BM and PBSC resulted in a mean OS
      of 30 months. The antigen 17-1A was detected on most CK+ cells in both patient
      groups before therapy, on all CK+ PBSC and on CK+ cells in group 2 patients after
      therapy. Increased Her-2/neu levels were found in group 2 patients before
      chemotherapy. In conclusion, micrometastatic cells are present in blood and PBSC
      grafts of high-risk breast cancer patients and can survive even HD-chemotherapy.
      Immunotherapeutic target antigens on the cell surface of these cells support the
      idea that a combined chemoimmunotherapy might be successful in eliminating
      minimal residual disease.

PMID- 11956601
TI  - NDPP1 is a novel CARD domain containing protein which can inhibit apoptosis and
      suppress NF-kappaB activation.
AB  - We have identified several novel human caspase recruitment domain (CARD)
      containing genes. In this report, we describe one among them, NDPP1. The mRNA
      expression of NDPP1 was higher in the kidney and testis of normal tissues. High
      expression was also detected in breast cancer, prostate cancer and granulosa
      tumor cells but not in bladder cancer cells. Transfection experiments
      demonstrated that NDPP1 was able to supress Bax-induced apoptosis in REF52 cells.
      Furthermore, NDPP1 is able to inhibit NF-kappaB activation induced by TNF-alpha
      treatment in HepG2 cells. Our results demonstrated that NDPP1 is a novel member
      of the CARD family and a negative regulator of cell death and inflammatory
      response. The NDPP1 locus has been assigned to chromosome 19q13.3. The NDPP1 gene
      consists of 14 exons and transcribts for at least five splicing variants.

PMID- 11956602
TI  - MIB-1, p53, bcl-2, and WAF-1 expression in pelvic lymph nodes and primary tumors
      in early stage cervical carcinomas: correlation with clinical outcome.
AB  - A complete series of 40 cervical carcinomas with pelvic lymph node metastases
      were analysed immunohistochemically for prognostic markers. The aims of this
      study were to examine whether the detection of MIB-1, p53, bcl-2, and WAF-1 could
      be used as a prognostic marker for tumor recurrence and survival rate. During the
      period of observation (mean 222, range 72-360 months) 22 (55%) recurrences were
      encountered and 20 patients died of the disease. There were 35 squamous cell
      carcinomas (87.5%), 2 adenosquamous carcinomas (5.0%), and 3 pure adenocarcinomas
      (7.5%). One tumor (2.5%) was well differentiated, 12 tumors (30%) were moderately
      differentiated, and 27 tumors (67.5%) were poorly differentiated. The primary
      tumor grade (P=0.037) and radicality of the surgical margins (P=0.021) were
      significant prognostic factors with regard to tumor recurrence. The site and
      number of lymph nodes with metastases had no prognostic value. P53, bcl-2, and
      WAF-1 were not predictive factors for recurrences or the cancer-specific survival
      rate. The concordant expression of WAF-1 in the primary tumor and in lymph node
      metastases was lower than for p53 and bcl-2. The proliferative activity (MIB-1)
      seemed to be lower in tumor cells metastasized to the pelvic lymph nodes than in
      cells of the primary tumor. Expression of MIB-1 in lymph nodes was predictive of
      disease-free survival in both univariate and multivariate proportional hazard Cox
      analyses.

PMID- 11956603
TI  - Single static view 99mTc-sestamibi scintimammography predicts response to
      neoadjuvant chemotherapy and is related to MDR expression.
AB  - We examined the relevance of a pre-treatment single static view 99mTc-sestamibi
      scintimammography and expression of multidrug resistance proteins as predictors
      of response to neoadjuvant chemotherapy for invasive breast cancer. Forty-five
      patients affected by primary breast cancer underwent clinical examination,
      mammography, sonography, 99mTc-sestamibi scintimammography, and biopsy for
      histopathological diagnosis before neoadjuvant chemotherapy. Expression of MDR1
      and MRP mRNA were determined by RT-PCR on fine-needle aspirations. Following
      completion of anthracycline-based chemotherapy, clinical, mammographic,
      sonographic and pathological responses were determined. 99mTc-sestamibi
      scintimammography predicted the reduction of tumor size measured by sonography
      and the pathological response according to Sataloff classification (p<0.05) and
      tend to predict pathological response according to Chevallier (p<0.1). A negative
      99mTc-sestamibi scintimammography predicted chemoresistance with a specificity of
      100%. Uptake of 99mTc-sestamibi was inversely correlated to the expression of
      MDR1 (p<0.05) in invasive ductal carcinoma. A pre-treatment single-view 99mTc
      sestamibi scintimammography is an excellent predictor of MDR1 chemoresistance and
      was highly specific of a lack of pathological response to chemotherapy.

PMID- 11956604
TI  - Internalisation and retention of EGF-dextran associated radioactivity in
      transfected Chinese hamster ovary cells expressing the human EGF-receptor.
AB  - Chinese hamster ovary (CHO) cells transfected with the wild-type gene for the
      human epidermal growth factor-receptor (EGFR) and expressing the receptor in
      their cell membrane are, together with the receptor negative parent CHO cells, an
      interesting model system for experimental EGFR-targeting tumour therapy.
      Comparisons of effects on nearly identical cells with and without receptors can
      be made. The main purpose of this work was to compare the internalisation and
      retention of the radioactivity delivered as 125I-EGF or 125I-EGF-dextran in
      transfected cells (called CHO-EGFR), and human glioma cells U-343 which naturally
      express wild-type EGFR. We found that radioactivity delivered as 125I-EGF-dextran
      was retained intracellularly by both cell types to a higher degree than
      radioactivity delivered as 125I-EGF. Prolonging the cellular exposure time for
      125I-EGF-dextran considerably increased postincubation intracellular retention in
      both cell types. No major differences between the two EGFR expressing cell lines
      were found and, based on the results in this work, CHO-EGFR cells seem an
      adequate model for experiments with agents targeting the EGF-receptor.

PMID- 11956605
TI  - The incidence of thyroid abnormalities in adults irradiated for lymphoma.
AB  - The aim of the study was to investigate the incidence of thyroid abnormalities in
      neck irradiated lymphoma patients. Of the 298 patients who had irradiation to the
      neck for lymphoma between 1966-1988, 174 were found to be alive and free of
      disease. These patients were invited to participate in the study. From the 174,
      93 were able to participate (group 1). Two control groups were recruited; both
      were sex and aged matched. One group (group 2) consisted of lymphoma patients who
      were treated with chemotherapy (n=39) or irradiation to areas other than the neck
      (n=16). The other group (group 3) consisting of healthy volunteers (n=35)
      recruited from hospital staff and minor surgery attendees, had never had lymphoma
      or radiotherapy. All participants were required to complete a past medical
      history and thyroid symptom questionnaire, had blood taken for assays of thyroid
      stimulating hormone (TSH), thyroglobulin antibodies, thyroid peroxidase
      antibodies, sodium iodide symporter antibodies and TSH receptor antibodies and
      underwent ultrasound and clinical examination of the neck. A significant
      percentage of patients who had been irradiated in the neck had abnormalities on
      ultrasound, compared to groups 2 and 3 (77% vs 42% vs 24%). Abnormal TSH levels
      were found to be significantly more common in neck irradiated patients compared
      to the other groups (50% vs 9% vs 5%). There is a clear difference between neck
      irradiated patients and control groups. The importance of screening irradiated
      patients for thyroid abnormalities is re-emphasised.

PMID- 11956606
TI  - Potassium antimonyl tartrate induces reactive oxygen species-related apoptosis in
      human myeloid leukemic HL60 cells.
AB  - Potassium antimonyl tartrate (PAT), like arsenic trioxide (As2O3), has recently
      been shown to exert cytotoxicity towards acute promyelocytic leukemia (APL)
      cells. In the present study, we demonstrated that PAT treatment also inhibited
      cell growth of four acute myeloid leukemia (AML) cell lines, i.e., HL60, K562,
      KG1a and U937, that do not derive from APL. PAT, like As2O3, was further shown to
      induce apoptosis in HL60 cells as assessed by Hoechst 33342 staining and
      microscopical detection. Such an apoptotic process was associated with loss of
      mitochondrial potential and enhanced cellular production of reactive oxygen
      related species; it was potentiated by co-treatment with buthionine sulfoximine,
      a pro-oxidant compound acting through inhibition of glutathione synthesis, and
      abolished in response to the antioxidant N-acetylcysteine, thus outlining that
      the toxicity of PAT, similarly to that of As2O3, is modulated by the cellular
      redox status. Pan-caspase inhibitors failed to inhibit PAT-triggered apoptosis of
      HL60 cells whereas they fully blocked that linked to As2O3, suggesting that PAT,
      unlike As2O3, does not require caspase activity for inducing apoptosis. PAT and
      As2O3 also differently affected intracellular pH, a key parameter commonly
      altered during apoptotic processes. Such data therefore indicate that PAT can
      exert cytotoxicity towards AML cells not deriving from APL such as HL60 cells,
      through inducing an apoptotic process which exhibits some similarities and some
      differences with that triggered by As2O3.

PMID- 11956607
TI  - Granulocyte macrophage-colony stimulating factor gene transfer to induce a
      protective anti-tumoral immune response against the 9L rat gliosarcoma model.
AB  - The injection of irradiated tumor cells genetically engineered to express the
      granolocyte macrophage-colony stimulating factor (GM-CSF) is reported as
      stimulating antitumoral immunity in several animal models. We used the 9L
      gliosarcoma rat model to investigate the potency of this strategy in relation to
      the central nervous system. After in vitro transduction experiments to generate
      9L murine cells producing GM-CSF (9LmGM-CSF cells), we found that with the
      exception of one rat subcutaneously (s.c.) grafted with 108 9LmGM-CSF cells,
      syngenic rats s.c. injected (dorsal route) with 106-108 viable 9LmGM-CSF cells
      did not develop s.c. 9L gliosarcomas, while rats s.c. grafted with the same
      number of naive 9L cells died between 25 and 45 days postgraft. Intracerebral
      stereotactic injections of 4.104 naive 9L (without s.c. 9LmGM-CSF treatment)
      killed all the rats within 18-24 days, while s.c. grafting with 108 9LmGM-CSF
      cells wholly prevented the development of 9L brain gliosarcomas. These results
      outline the feasibility of the GM-CSF gene transfer approach in glioma (or at
      least gliosarcoma) gene therapy and could therefore serve as a basis for the
      development of an adjuvant treatment of glioblastomas using GM-CSF-producing
      tumor cell vaccines.

PMID- 11956608
TI  - Growth reduction of a xenotransplanted human soft tissue sarcoma by MDM2
      antisense therapy via implanted osmotic minipumps.
AB  - The MDM2 oncogene plays an important role in tumorigenesis and especially in soft
      tissue sarcomas (STS). Overexpression of the MDM2 protein is associated with a
      poorer prognosis for STS patients. An MDM2 antisense approach to reduce MDM2
      protein levels has been successfully applied on several carcinomas in vitro and
      used on a few in vivo cases. However, antisense treatment not only resulted in an
      MDM2 protein reduction but also in a wild-type P53 gene (wt-P53) mediated tumor
      growth suppression due to its genetic wt-P53 status. In this study, we used a
      clinically relevant xenotransplanted STS model with a mutated P53 gene (mt-P53)
      in order to exclude the influence of wt-P53. The human STSs were surgically
      implanted and one week later osmotic pumps were implanted intraperitoneally into
      nude rats releasing MDM2-antisense ODNs (AS ODNs) continuously for one week. As
      controls MDM2-sense ODN (SE ODN) or a 0.9% NaCl solution (saline solution) were
      administered. After one week animals treated with MDM2-AS ODN (100 or 200 microg)
      showed a reduction in tumor mass in comparison to animals treated with MDM2-SE
      ODN. The reduction in tumor mass was significant in animals treated with MDM2-AS
      ODNs in comparison to the saline solution treated ones (p=0.018 or p=0.007).
      Furthermore, a significant reduction in macroscopically visible tumor number with
      MDM2-AS ODN treatments (100 or 200 microg) in comparison to MDM2-SE ODN or saline
      solution treatment (both p=0.009) was observed for the first time. As expected a
      reduction in MDM2 protein expression in the MDM2-AS ODN treated tumors when
      compared to the MDM2-SE ODN or saline solution treated tumors was detected in
      Western blot analyses and immunohistochemically. In addition, an unexpected
      reduction in mt-P53 protein expression after AS ODN therapy was also observed. In
      short, we have demonstrated in vivo for the first time that MDM2-AS ODN treatment
      of xenotransplanted STS (mt-P53) reduces tumor mass, tumor number, MDM2 protein
      and mt-P53 protein expression. Our findings support the hypothesis that MDM2-AS
      ODN treatment may exert a tumor inhibiting effect on all MDM2 expressing tumors
      regardless of the P53-status, this in turn may be of general importance in gene
      therapy of cancer.

PMID- 11956609
TI  - Lymphatic vessels and lymphangiogenesis in female cancer: mechanisms, clinical
      impact and possible implications for anti-lymphangiogenic therapies (Review).
AB  - Lymphatic vessels play a crucial role in a variety of human cancers, since
      invasion of lymphatic vessels by tumor cells and subsequent development of lymph
      node metastases significantly influences prognosis of cancer patients and
      therefore represent an integral part of tumor staging. Recent evidence on the
      important influence of lymphangiogenetic growth factors on intralymphatic cancer
      growth and metastasis raises hopes that lymphatic vessels and factors inducing
      their growth could serve as an additional target for tumor therapy. Nevertheless,
      in contrast to blood vessel angiogenesis, the mechanisms of new lymphatic vessel
      formation in human cancers, i.e. lymphangiogenesis, are still relatively unclear.
      In addition, only little data exist so far on the quantification and impact of
      this lymphangiogenesis, evident by lymphatic microvessel density (LMVD), on the
      prognosis of cancer patients. With expectation of possible anti-lymphangiogenic
      therapies, this review focuses on the mechanisms of lymphangiogenesis in general,
      and especially on the role of lymphatic vessels in gynecological and breast
      cancer, which are the so far most detailed investigated malignancies with regard
      to lymphangiogenesis.

PMID- 11956610
TI  - Internal mammary sentinel node biopsy for breast cancer: is it practicable and
      relevant? (Review).
AB  - Sentinel lymph node (SLN) biopsy is a useful way of assessing axillary nodal
      status and obviates unnecessary axillary lymph node dissection for patients with
      node-negative breast cancer. However, SLN can also be located in the internal
      mammary lymph node (IMN) chain or elsewhere. The practicability and relevance of
      internal mammary SLN is reviewed and discussed. Axillary and IMN status have
      similar predictive value for survival, and the involvement of IMNs has prognostic
      value for both axillary node-negative and node-positive patients. Although
      parasternal recurrence is fortunately rare after modified radical mastectomy or
      breast conserving surgery, if left untreated it develops not infrequently as a
      clinically evident disease in patients with histologic involvement of IMNs.
      Internal mammary SLNs can be identified by means of lymphoscintigraphy and gamma
      detection probe after peritumoral injection of radioisotopes. A positive internal
      mammary SLN biopsy would be an indication for internal mammary radiotherapy as
      well as adjuvant systemic treatment. However, the reported incidence of positive
      internal mammary SLNs is still lower than expected, because the spread of
      radioisotope activity is not synonymous with nodal positivity. Internal mammary
      SLN biopsy is considered to be still in the investigative stage. More data are
      needed on the correction of a internal mammary SLN and pathologic positivity, so
      that further clinical investigation is clearly warranted.

PMID- 11956611
TI  - Breast-conservation treatment for bilateral breast cancer in five Japanese women.
AB  - Between August 1989 and September 1999, breast-conservation treatment (BCT) was
      performed in 250 of 256 breast cancer patients. Five of the 250 patients had
      bilateral breast cancer, and 4 with synchronous bilateral breast cancer of the 5
      were concomitantly treated by chemo-endocrine therapy before simultaneous breast
      conservation surgery for bilateral breast cancer. Chemotherapy was performed
      using cyclophosphamide, pirarubicin, and 5-fluorouracil, while endocrine therapy
      was performed using an antiestrogen agent (tamoxifen or toremifene). All patients
      were also treated by radiotherapy. Since no severe side effects or complications
      were induced by these therapeutic approaches, bilateral breast cancer may be
      successfully treated by BCT as in unilateral breast cancer. However, of the 5
      patients with bilateral breast cancer, cancer recurrence in the axillary lymph
      nodes was detected only in 1 patient with T2N1 cancer 78 months after
      simultaneous breast-conservation surgery for bilateral breast cancer.

PMID- 11956612
TI  - An elderly patient with DCIS of the breast effectively treated with toremifene
      alone.
AB  - An elderly patient with breast cancer received toremifene monotherapy for one
      year, and about 60% tumor remission rate was obtained. Since viability of the
      residual tumor was suspected on ultrasonography (US), computed tomography (CT),
      and magnetic resonance imaging (MRI), lumpectomy was performed under local
      anesthesia. The histopathological diagnosis was ductal carcinoma in situ (DCIS).
      The patient did not undergo axillary lymph node dissection or systemic
      chemotherapy. The patient is alive without disease under postoperative
      radiotherapy and toremifene treatment. Toremifene monotherapy and/or preoperative
      adjuvant therapy with toremifene alone may be useful methods for elderly patients
      with breast cancer considering the patients' quality of life.

PMID- 11956613
TI  - Thymidine phosphorylase and dihydropyrimidine dehydrogenase levels in primary
      colorectal cancer show a relationship to clinical effects of 5'-deoxy-5
      fluorouridine as adjuvant chemotherapy.
AB  - Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR,
      doxifluridine), an intermediate metabolite of capecitabine, to 5-fluorouracil (5
      FU). While dihydropyrimidine dehydrogenase (DPD) catalyzes 5-FU to inactive
      molecules. We investigated TP and DPD levels in tumor tissue to assess their
      clinical significance as indicators for selecting colorectal cancer patients for
      5'-DFUR adjuvant chemotherapy. A total of 88 colorectal cancer patients were
      classified into Dukes' B and C groups and treated for 2 years with oral 5'-DFUR
      (800 mg/body/day). During the follow-up period, 20 of the 88 patients developed a
      recurrence. All the patients were examined retrospectively for primary tumor TP
      and DPD levels and clinical response to 5'-DFUR. Results showed that: a) median
      levels of TP and DPD in the primary tumor, measured by enzyme-linked
      immunosorbent assay (ELISA), were, respectively, 43.6 and 32.3 U/mg protein.
      Primary tumor TP levels of the 20 patients who had a recurrence were lower than
      those of the 68 patients with no recurrence (p=0.07); b) although there were no
      significant differences in clinicopathologic features between high and low median
      TP level groups, disease-free survival was better in the high TP than in the low
      TP group (89% vs. 64%, at year 4); and c) of patients classified into 4 groups
      such as high TP/DPD, high TP but low DPD, low TP but high DPD, and low TP/DPD,
      patients with high TP but low DPD had the best disease-free survival, whereas the
      low TP but high DPD group had the worst survival. These results suggest that TP
      and DPD levels in primary colorectal tumors may be a useful indicator for
      selecting patients likely to respond to 5'-DFUR adjuvant chemotherapy and
      probably capecitabine, a prodrug of 5'-DFUR.

PMID- 11956614
TI  - Endometrial cytodiagnosis using a new softcyte versus a conventional endocyte.
AB  - A new endometrial cytologic sampling device, softcyte, was used in cytological
      screening for endometrial cancer, and was compared with the endocyte with regard
      to manipulability, adverse effects (including pain and hemorrhage), and cellular
      findings (including the quantity of cells collected, the success rate, cell
      freshness, and cellular clumping). A total of 315 women (premenopause 251,
      postmenopause 64) were randomly assigned to two groups who underwent the
      endometrial cytological screening with either the softcyte or the endocyte. To
      assess the value of the softcyte we compared it with the endocyte. Endometrial
      cytology using a softcyte or an endocyte achieved high correct diagnosis rate for
      cancer, and both instruments are valuable as endometrial cytologic sample
      devices. The softcyte causes only mild pain on introduction and during
      collection, and a large quantity of cells could be harvested. These results
      suggest that the softcyte is a useful cytologic sampling device in screening for
      endometrial cancer.

PMID- 11956615
TI  - Clinical significance of angiogenesis in rectal carcinoid tumors.
AB  - This study was designed to examine angiogenesis in rectal carcinoid tumors in
      relation to the clinicopathologic features. Seventy-seven rectal carcinoid tumors
      were studied clinicopathologically and experimentally. Cellular proliferation and
      microvessel density (MVD) were examined immunohistochemically. We used the
      antibodies MIB-1 for Ki-67, DO7 for p53, and NU-4A1 for CD34 expression in this
      study. Ki-67 labeling index (LI) of all lesions was below 3%, and the median Ki
      67 LI of all lesions was 0.68+/-0.70% (mean +/- SD). A correlation was recognized
      between tumor size, metastasis and Ki-67 LI (p<0.05). Median MVD of all lesions
      was 25.9+/-13.1 (mean +/- SD). MVD was correlated with the tumor size (p<0.01),
      presence of depression (p<0.01), lymphatic (p<0.01) or venous (p<0.05) invasion,
      and existence of metastasis (p<0.01). But there was no significant relationship
      between MVD and Ki-67 LI. p53 protein was detected sporadically in only 1 case
      (1.3%) demonstrating both liver and lymph node metastases. Rectal carcinoid
      tumors are slow-growing tumors with a lower proliferative activity. Angiogenesis
      plays an important role in progression of rectal carcinoid tumors independent of
      the cellular proliferative activity.

PMID- 11956616
TI  - Immunohistochemical expression of SKALP/elafin in squamous cell carcinoma of
      human lung.
AB  - The immunohistochemical expression of skin-derived anti-leukoproteinase
      (SKALP)/elafin in lung squamous cell carcinoma (SqCC) and in uninvolved bronchial
      epithelium was studied. The results were compared with the immunohistochemical
      staining of proliferating cell nuclear antigen (PCNA) and the TDT-mediated dUTP
      digoxigenin nick end labeling (TUNEL) assay. SKALP/elafin was expressed in SqCC
      with high incidence (82.6%). By contrast, the expression was not observed in
      uninvolved bronchial epithelium. SKALP/elafin expression was located in the cell
      layers just underneath the cornified envelope of each cell nest, and DNA
      fragmentation was observed in the same cell layers. PCNA was expressed in the
      basal layer of each cornified envelope, and both expressions were clearly
      separated. Immunoreactive score of SKALP/elafin expression was significantly
      correlated with the differentiation and it tended to increase in accordance with
      the degree of differentiation. These results suggested that SKALP/elafin was
      possibly involved in the cell differentiation program, finally leading to
      keratinization in SqCC of human lung. SKALP/elafin may be a beneficial molecular
      target for detection or even the development of a new therapeutic method against
      cancer.

PMID- 11956617
TI  - Expression and prognostic significance of S100A2 protein in squamous cell
      carcinoma of the esophagus.
AB  - The purpose of this study was to evaluate the expression of S100A2 Ca2+-binding
      protein and its prognostic significance in the management of squamous cell
      carcinoma of the esophagus. Changes in cytosolic Ca2+ concentration control a
      wide range of cellular responses including cellular apoptosis. Intracellular S100
      Ca2+-binding proteins are key molecules in transducing Ca2+ signaling. Among
      these, S100A2 has recently attracted major interest due to its stable expression
      in normal epithelia and down-regulation in some tumors. As a candidate tumor
      suppressor, expression of S100A2 has been proposed as a valuable prognostic
      marker in different tumors. We examined the clinical significance of S100A2
      expression in 116 resected specimens of esophageal squamous cell carcinomas
      (ESCC) using immunohistochemistry. S100A2 was positive in 49 cases (42.2%) and
      its expression was significantly higher in large (p=0.01) and well differentiated
      tumors (p=0.013). Lymph node-positive tumors had a lower expression of S100A2
      protein in comparison to the corresponding lymph node negative equivalents in
      each of the T stages, but the difference was statistically significant (p=0.041)
      only for the T1b tumors. S100A2 status became an independent predictor of patient
      survival (p=0.026) in lymph node-negative cases but not in node-positive cases.
      Evaluation of S100A2 protein expression may play an important role in the
      management of ESCC. The node-negative ESCC patients without S100A2 expression
      might be a high-risk group with poor survival and will need further attention to
      design appropriate adjuvant therapy.

PMID- 11956618
TI  - Expression of intercellular adhesion molecule-1 and prognosis in colorectal
      cancer.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is a 90-kDa cell surface glycoprotein
      and is known to be a member of the immunoglobulin gene superfamily of adhesion
      molecules. It has been suggested that ICAM-1 expression on cancer cells might
      have a role as a suppressor of tumor progression under the host immune
      surveillance system. We studied the correlation between the expression of ICAM-1
      and clinicopathological factors, as well as infiltration of tumor infiltrating
      lymphocytes (TILs) in colorectal cancer. Resected specimens from 96 patients with
      colorectal carcinoma were investigated using immunohistochemical staining with a
      monoclonal antibody against ICAM-1. As a result, the incidence of lymph node or
      liver metastasis was significantly lower in patients with ICAM-1-positive tumors
      than in those with ICAM-1-negative tumors. Infiltration of TILs was more
      frequently observed in the ICAM-1-positive tumors than in the ICAM-1-negative
      tumors. The prognosis of the patients with ICAM-1-negative tumors was
      significantly poorer than that of those with ICAM-1-positive tumors. In
      conclusion, these findings suggested that ICAM-1 expression is closely associated
      with metastasis and may be a useful indicator of prognosis in patients with
      colorectal cancer.

PMID- 11956619
TI  - Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell
      lung cancer.
AB  - Recently, by using differential display on specimens of non-small cell lung
      cancer (NSCLC), we detected overexpression of dihydrodiol dehydrogenase (DDH)
      that was rarely expressed in the corresponding normal lung tissue. DDH
      overexpression was correlated with poor prognosis of patients with advanced
      NSCLC. Because DDH could metabolize polycyclic aromatic hydrocarbons (PAH) in the
      liver, DDH overexpression in NSCLC would suggest an association with
      carcinogenesis and disease progression. In this study, we investigated DDH
      expression in 103 patients with resected stage I NSCLC. Expression of DDH was
      detected by using immunohistochemistry. Relation between DDH expression and
      clinicopathological parameter (age, gender, smoking habit, tumor status,
      histological type, cell differentiation, local recurrence, distant metastasis or
      survival) was analyzed by statistical analysis. DDH overexpression was detected
      in 39 (37.9%) of 103 pathological sections. Frequency of DDH overexpression was
      significantly higher in male patients (p=0.043) and patients with squamous cell
      carcinoma (p<0.005). Among 103 patients, 14 patients had local recurrence and 28
      patients had distant metastasis during follow-up examination. The 5-year survival
      rate of these patients was poorer than those who did not have local recurrence or
      distant metastasis (both were p<0.005, respectively). Although patients with low
      DDH expression had more favorable outcome than those with DDH overexpression, in
      terms of survival rate no statistical significance was detected (p=0.889). The
      results suggest that DDH expression may serve as an early but not prognostic
      biomarker for patients with resectable stage I NSCLC.

PMID- 11956621
TI  - Interleukin 8 and Flt3 ligand as markers of advanced disease in primary
      gastrointestinal non-Hodgkin's lymphoma.
AB  - Tumor angiogenesis plays a significant role in cancer growth and metastasis. This
      complex process is influenced by a variety of angiogenic factors. Elevated serum
      levels or high expression of some of these factors have been shown to correlate
      with stage and prognosis in certain human malignancies. This has been
      demonstrated most consistently for vascular endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF). We tried to establish, whether pre
      treatment serum levels of the angiogenic factors VEGF, bFGF, interleukin 8 (IL-8)
      and Flt3 ligand (Flt3L) correlate with prognostic variables in 30 patients with
      primary gastro-intestinal non-Hodgkin's lymphoma. Our results suggest that higher
      pretreatment serum levels of IL-8 and Flt3L are associated with higher stage
      (>or= II) and high grade, respectively. Elevated pretreatment serum levels of
      VEGF and bFGF were not associated with advanced disease characteristics and
      carried no prognostic information.

PMID- 11956620
TI  - Immunohistochemical expression of cytokine induced nitric oxide synthase in
      colorectal carcinoma.
AB  - Significance of expression of cytokine induced nitric oxide synthase (iNOS) in
      colorectal carcinoma remains controversial. The aim of the current study was to
      elucidate the significance of immunohistochemical expression of iNOS in
      colorectal carcinoma. The subjects were the 54 patients with colorectal
      carcinoma, including 13 with obstructing carcinoma. The immunohistochemical
      expression of iNOS was examined and the clinicopathological data were compared
      between iNOS-positive and iNOS-negative carcinomas. Of 54 colorectal carcinomas,
      there were 27 tumors with iNOS expression. The proportion of tumors occurring in
      the rectum was significantly lower in iNOS-positive carcinomas than in iNOS
      negative carcinomas (p=0.028). The incidence of lymph node metastasis and
      lymphatic invasion in colorectal carcinomas with iNOS expression (63.0%, 17 out
      of 27 and 96.3%, 26 out of 27, respectively) were significantly more frequent
      than those in carcinomas without iNOS expression (29.6%, 8 out of 27 and 70.4%,
      19 out of 27, respectively) (p=0.013 and p=0.011, respectively). The proportion
      of obstructing carcinoma in tumors with iNOS expression (37.0%, 10 out of 27) was
      significantly higher than that in tumors without iNOS expression (11.1%, 3 out of
      27; p=0.020). Our results could suggest that iNOS expression can be an indicator
      of malignant potential in colorectal carcinoma and that it may be one of the
      biological features of obstructing carcinoma of the colon and rectum. Moreover,
      our results demonstrated that nitric oxide might be associated with the
      difference in the mechanism of carcinogenesis in the colon and the rectum.

PMID- 11956622
TI  - Poly(ADP-ribose) polymerase turnover alterations do not contribute to PARP
      overexpression in Ewing's sarcoma cells.
AB  - Ewing's sarcoma (EWS) cells contain significantly higher levels of poly(ADP
      ribose) polymerase (PARP) mRNA, protein and enzymatic activities than any other
      eukaryotic cells. Evidence from our laboratory showed that increased
      transcription, rather than mRNA stability, contributes to the elevated PARP
      levels. It has been proposed that alterations in the normal turnover rate of PARP
      may also contribute to the total cellular PARP content as well as to the
      apoptotic response of Ewing's sarcoma cells to ionizing radiation. To address
      this possibility, we compared the turnover of PARP in EWS cells (A4573), which
      contain high PARP and are relatively radiosensitive, with that in laryngeal
      squamous cell carcinoma cells (SQ-20B), which have low PARP and are
      radioresistant. Results showed that PARP turnover parameters are nearly identical
      in both cells types. These data conclusively demonstrate that PARP turnover is
      not a determinant of either the elevated PARP content or the radiation response
      of EWS cells.

PMID- 11956623
TI  - Prevention of methylnitrosourea-induced mammary cancers by 9-cis-retinoic acid
      and/or vitamin D3.
AB  - Two cancer chemopreventive agents, vitamin D3 and 9-cis-retinoic acid (9-cis-RA),
      were evaluated alone and in combination in the methylnitrosourea (MNU)-induced
      mammary cancer model. In this study, female Sprague-Dawley rats received MNU (50
      mg/kg BW) at 50 days of age. Vitamin D3 and 9-cis-RA were administered in the
      diet beginning three days later. The groups were: Group 1, vehicle only; Group 2,
      9-cis-RA (60 mg/kg diet); Group 3, vitamin D3 (10 microg/kg diet); Group 4,
      vitamin D3 (3.3 microg/kg diet); Group 5, 9-cis-RA (60 mg/kg diet) plus vitamin
      D3 (10 microg/kg diet); and Group 6, 9-cis-RA (60 mg/kg diet) plus vitamin D3
      (3.3 microg/kg diet). Animals were observed daily for signs of toxicity and were
      palpated 2x/week for mammary tumors. The study was terminated 150 days after
      treatment with MNU. The average number of mammary cancers was 6.7 in the animals
      receiving only the carcinogen. 9-cis-RA alone caused a 23% decrease in mammary
      cancer multiplicity, while vitamin D3 alone actually caused slight increases of
      17 and 16% at 10 and 3.3 microg/kg diet dose levels, respectively. When the
      agents were given in combination, however, the 9-cis-RA plus the high dose of
      vitamin D caused a statistically significant decrease (44%) in mammary cancer
      number, while the 9-cis-RA plus the low dose resulted in a 37% decrease. Thus,
      low doses of these agents that were not effective in preventing mammary cancer
      when given alone appeared to be active when given in combinations. Possible
      interactions between the retinoic acid receptors and vitamin D receptor may be
      responsible for the observed inhibition of mammary carcinogenesis.

PMID- 11956624
TI  - New attempt of preoperative differential diagnosis of thyroid neoplasms by
      telomerase activity measurement.
AB  - Telomerase activity (TA) has been shown highly expressed in various solid
      malignant neoplasms, but only rarely in benign tumor or normal tissues. Most
      reports examined TA by the qualitative method, telomeric repeat amplification
      protocol (TRAP) assay. We examined TA in tissues of thyroid neoplasm by
      quantitative method to establish whether TA was a useful marker for preoperative
      differential diagnosis of thyroid tumors. TA was measured by the quantitative
      method, TRAP assay, fluorescence based TRAP method in 32 frozen tissues of
      thyroid tumors (17 malignant, 15 benign). Cut-off values in TA were 0 unit and 9
      units from mean +/- 2SD of TA in benign thyroid tumors. Mean (SD) TA levels in
      benign thyroid tumors and thyroid carcinomas were 2.06 (3.58) units and 30.5
      (38.2), respectively. Mean TA of carcinomas was significantly higher than that of
      benign disease in thyroid tumors (p=0.0092). The sensitivity of the malignancy
      was 64.7% (cut-off <0) (p=0.162), 52.9% (cut-off <9) (p=0.0048). TA in thyroid
      carcinoma was significantly correlated with UICC stage (p=0.029), and slightly
      correlated with tumor size, pN and M. Positive rate of TA in microfollicular
      adenoma was slightly higher than that in macrofollicular adenoma. Conclusively,
      quantitative TA might be a useful marker for differential diagnosis between
      benign and malignant thyroid tumors.

PMID- 11956625
TI  - Molecular staging of pelvic surgical margins after radical prostatectomy:
      comparison of RT-PCR for prostate-specific antigen and telomerase activity.
AB  - The further course of prostate cancer (PC) after radical prostatectomy (RPX) is
      decisively influenced by the local tumor stage. Although it is now possible to
      assess the risk of local recurrence from the histopathology, precise predictions
      cannot be made. A more accurate evaluation would be desirable, mainly for early
      planning of adjuvant therapy. We assessed the detection of telomerase activity
      using the Telomeric Repeat Amplification Protocol in surgical margins compared to
      RT-PCR-supported prostate-specific antigen (PSA) mRNA detection and conventional
      histopathological examination. We examined 95 patients with local PC during RPX
      and 16 patients with muscle-invasive transitional bladder cancer who underwent
      radical cystectomy. After RPX or RCX biopsies were obtained from 4 or 3 defined
      areas of the prostatic fossa and processed by TRAP assay for telomerase activity
      and by RT-PCR for PSA using a standard protocol. Five of 48 patients (10.4%) with
      organ-confined prostate cancer (pT2) and 7 of 47 patients (14.9%) with locally
      advanced PC (>pT2) had positive detection of telomerase activity in at least one
      positive specimen. In contrast to RT-PCR for PSA mRNA and histological findings
      for organ-confined and locally advanced disease, detection of telomerase activity
      yielded no statistically significant correlation to clinical parameters. Only PC
      patients with positive histopathological margins had a positive correlation
      between detection of telomerase activity and high Gleason scores (r=0.65,
      p=0.022). Based on the results obtained and the current state of knowledge,
      measurement of telomerase activity must be considered less sensitive than RT-PCR
      for PSA mRNA in surgical margins, although tumor specificity should theoretically
      be higher. It is not even sure at the present time whether a combination of both
      methods offers any recognizable advantage over PSA mRNA detection alone. The
      value of the results obtained in this study will have to be assessed in a further
      follow-up to determine whether patients with positive molecular detection have an
      increased risk of local recurrence.

PMID- 11956626
TI  - Allelic deletions of Rb and L-myc in urine sediments from patients with bladder
      tumors or carcinoma in situ.
AB  - In a previous study we found allelic imbalances of Rb and L-myc associated with
      disease stage and disease course in bladder cancer. The primary aim of the
      present study was to determine whether the changes found in tumors were reflected
      in urine sediments. Secondly we wanted to test if Rb and L-myc were frequently
      lost in urine sediments from patients with carcinoma in situ and no bladder tumor
      at present. Based on this we examined allelic deletions of the Rb and L-myc genes
      in tumor and urine from 55 patients with bladder tumors or carcinoma in situ.
      Deletions were examined on extracted DNA from tumors and urine sediments by the
      use of microsatellite markers located as close to the genes as possible. Fifty
      five patients and 10 controls were included. We found no strict correlation
      between allelic deletions in bladder tumors and urine sediments from the same
      patient. Allelic deletions in urine sediments were at least as common in patients
      with carcinoma in situ and no bladder tumor (32%) as in patients with bladder
      tumors (20%). It was possible to identify allelic deletions in urine sediment
      from 1 patient with cystitis and no history of malignant bladder disease (6%). In
      conclusion we found no strict correlation between allelic deletions in bladder
      tumors and urine sediments. Allelic deletions in urine sediments seem to be at
      least as common in patients with carcinoma in situ as in patients with bladder
      tumors.

PMID- 11956627
TI  - Distinct promoter usage of mdm2 gene in human breast cancer.
AB  - Human breast cancers, especially estrogen receptor alpha (ER(alpha))-positive
      ones, often overexpress the oncoprotein MDM2 without mdm2 gene amplification. The
      mdm2 gene is transcribed into two different mRNAs, namely L-mdm2 and S-mdm2,
      which are generated from promoters P1 (constitutive) and P2 (regulated by tumor
      suppressor p53), respectively. To cast light on the mechanisms of MDM2
      overexpression, we measured the expression levels of these mdm2 mRNAs using RT
      PCR analysis in three human breast cancer cell lines and 15 breast cancer samples
      obtained from surgery. ER(alpha)-positive MCF-7 cells, which possess wild-type
      p53, displayed dominant expression of S-mdm2. In contrast, two other cell lines
      with mutant p53, T47-D (ER(alpha)-positive) and MDA-MB-231 (ER(alpha)-negative),
      showed almost equivalent expression of L-mdm2 and S-mdm2. Treatment of 17beta
      estradiol (E2) significantly enhanced the expression of S-mdm2 but not that of L
      mdm2 in MCF-7. Among 6 breast cancer samples regarded as ER(alpha)-positive with
      wild-type p53, 5 samples showed increased expression of S-mdm2. Expression of S
      mdm2 was stimulated in 2 ER(alpha)-positive samples with mutant p53. In contrast,
      4 of 5 samples which express mutant p53 without ER(alpha) showed poor expression
      of S-mdm2. There is a tendency that ER(alpha)-positive breast cancers with wild
      type p53 preferably use P2 promoter for the expression of mdm2, possibly through
      E2-induced accumulation of p53. However, wild-type p53 and ER(alpha) are not
      necessarily enough for the utilization of S-mdm2. Tumors with mutant p53 also
      showed expression of S-mdm2 in some cases. These results strongly suggest that
      other factor(s) is also implicated in the promoter usage of mdm2 gene in human
      breast cancer tissues.

PMID- 11956628
TI  - Relationship between expression of matrix metalloproteinase-2 and matrix
      metalloproteinase-9 and invasion ability of cervical cancer cells.
AB  - Constitutive overexpression of matrix metalloproteinases (MMPs) is frequently
      observed in malignant tumors. MMPs are a family of zinc endopeptidases consisting
      of at least 20 different members. In particular, MMP-2 and MMP-9 are reported to
      be closely associated with invasion and metastasis in several cancers. We
      investigated whether expression of MMP-2 and MMP-9 is associated with invasion
      ability of seven cervical cancer cells by administration of o-phenanthroline as
      MMP inhibitor. In two cell lines, Siha and Caski, MMP-2 mRNA and protein were
      expressed at high levels. After treatment with o-phenanthroline, the rate of
      invasion in these two cell lines was significantly decreased. In contrast, in the
      other two cell lines, HT-3 and Caski, high levels of MMP-9 mRNA and protein were
      expressed but there was no decrease in the rate of invasion in these cells after
      treatment with o-phenanthroline. The data suggest that expression level of MMP-2
      mRNA may regulate with invasion ability of cervical cancer.

PMID- 11956629
TI  - Gingival metastasis in lung cancer.
AB  - Gingival metastasis is an extremely rare manifestation of lung cancer, and
      exhibits rapid growth with various clinical symptoms. Physicians must
      appropriately manage patients with lung cancer who develop gingival metastasis.
      Clinical records of patients with lung cancer treated at the Department of
      Internal Medicine II, Okayama University Hospital, between 1976 and 1998 were
      retrospectively reviewed. The medical literature was searched by Medline to
      identify reports of gingival metastasis from lung cancer. Three of 729 (0.41%)
      lung cancer patients developed gingival metastasis in our hospital between 1976
      and 1998, and 9 additional cases of this type of metastasis were found in the
      literature. All were male, and median age was 57.5 years (range, 47 to 70). There
      were no clear correlations between development of gingival metastasis and either
      histologic type or location of the primary lesion. Chemotherapy or radiotherapy
      was effective for treatment of gingival metastasis, and the quality of life was
      improved. However, survival after development of gingival metastasis was very
      short, with median survival of only 4 months.

PMID- 11956630
TI  - Do Ki67, S-phase, S + G2M and DNA ploidy, evaluated by flow cytometry, reveal
      locoregional metastasis in oral cavity and oropharynx carcinomas?
AB  - Tumour cell proliferation is an important biological prognostic parameter to be
      considered alongside clinical and histopathological parameters. It has been
      evaluated by immunohistochemistry using proliferative markers (PCNA, Ki67, etc.)
      and by flow cytometry considering DNA content, growth fraction (S + G2M) and S
      phase fraction. Our aim was to evaluate by flow cytometry both Ki67 and S-phase
      fraction, S + G2M, DNA content in patients surgically treated for oral cavity
      and/or oropharynx carcinomas. The study, performed on archival material, analysed
      the significance and prognostic reliability of these biological parameters to
      reveal locoregional metastasis and evaluated their possible correlation with
      clinical and histopathological parameters. In conclusion, tumour cell
      proliferation seems not to be useful in revealing the presence of locoregional
      metastasis in oral cavity and oropharynx carcinomas. Thus, new approaches are
      required.

PMID- 11956631
TI  - Cut-off levels of NSE to differentiate SCLC from NSCLC.
AB  - Neuron-specific enolase (NSE) is a specific tumor marker in small cell lung
      cancer (SCLC) patients, however, it has been reported that serum NSE levels are
      elevated in some patients with non-small cell lung cancer (NSCLC). To determine
      the most suitable cut-off level to distinguish between these two types of
      cancers, NSE levels were measured on serum samples of 417 patients with lung
      cancer without clinical information. Receiver operating characteristic (ROC)
      curve showed 14.5 ng/ml as a cut-off level and the 95 percentile serum NSE level
      in NSCLC was 20.5 ng/ml. None of the NSCLC patients had serum NSE levels more
      than 70 ng/ml. The measurement of serum NSE provides a discrimination between
      NSCLC and SCLC. If an NSCLC patient presents with a NSE level >20.5 ng/ml,
      pathological features must be examined with regard to the neuroendocrine
      differentiation.

PMID- 11956633
TI  - Prognostic value of combined analysis of estrogen receptor status and cellular
      proliferative activity in breast cancer patients with extensive lymph node
      metastases.
AB  - Breast cancer patients with four or more lymph node metastases generally show
      poor prognosis. However, some can survive for a long period. In this study, we
      retrospectively evaluated these cases for estrogen receptor status and cell
      proliferation potential in an attempt to predict patient outcome more accurately.
      Ninety-two radically operated primary breast cancer patients with four or more
      lymph node metastases were examined. High PCNA LI and ER-negative status were
      significantly associated with poor outcome. Then, survival analysis was performed
      on combination of ER and PCNA LI status, remarkable difference was shown in the
      prognosis of the patients.

PMID- 11956632
TI  - Expression of the TNF-alpha gene on mouse lung carcinoma cells suppresses
      spontaneous lung metastasis without affecting tumorigenicity.
AB  - Forced expression of TNF-alpha in tumor cells has been shown to inhibit their
      tumor growth in vivo through a number of mechanism such as activation of an
      immune system and induction of an apoptotic process. We re-examined the anti
      tumor effects caused by the TNF-alpha gene transfer using high-metastatic, murine
      lung carcinoma A11 cells. Expressed TNF-alpha molecules remained on cell surface
      and were not secreted into culture supernatants in vitro. Syngeneic
      immunocompetent mice developed tumors of TNF-alpha-expressed A11 cells and the
      growth of their subcutaneous tumors was not different from that of parent tumors.
      Spleen of the mice that developed TNF-alpha-expressed A11 tumors was
      significantly larger than that of the mice bearing parent tumors, but relative
      ratios of each cell population were not different. In contrast to subcutaneous
      tumors, the number of spontaneous lung foci metastasized from the subcutaneous
      TNF-alpha-expressed A11 tumors was markedly reduced compared with that from
      parent tumors. Expressed TNF-alpha on tumors is released by matrix
      metalloproteinases from surrounding tissues and anti-tumor effects by TNF-alpha
      can be influenced by local environmental conditions.

PMID- 11956634
TI  - Cross-linked collagen C- and N-telopeptides for an early diagnosis of bone
      metastasis from breast cancer.
AB  - Bone resorption markers have become available for the diagnosis of bone
      metastasis. We evaluated cross-linked collagen C-and N-telopeptides (ICTP and
      NTx) in diagnosing bone metastasis from breast cancer. For a threshold of 4.5
      ng/ml of 1CTP and 55.0 pmol BCE/micromol of NTx, bone metastasis could be
      predicted with an accuracy of 84% and 63%, respectively. All the patients who had
      metastatic lesions, but showed lower than 4.5 ng/ml of ICTP, had a solitary
      lesion of bone metastasis. Although ICTP is not sensitive enough to detect an
      early stage of bone metastasis, it is a better biochemical marker than NTx for
      detecting bone metastasis from breast cancer.

PMID- 11956635
TI  - Analysis of T cell receptors reactive with squamous cell carcinoma antigen SART-1
      presented by the HLA-A24 molecule.
AB  - We investigated the induction of cytotoxic T lymphocytes (CTLs) specific for
      squamous cell carcinoma antigen SART-1 from the peripheral blood mononuclear
      cells (PBMCs) of an HLA-A24 healthy donor by in vitro stimulation with dendritic
      cells (DCs) pulsed with the antigenic peptide. Effector cells, designated as
      <peptide-pulsed dendritic cell-activated killer (PDAK)> cells, exhibited potent
      cytotoxic activity against target cells in a SART-1-specific and HLA-restricted
      manner. T cell receptor (TCR) gene usage of the SART-1 PDAK cells analyzed by
      reverse transcribed-polymerase chain reaction (RT-PCR) and Southern blot analysis
      showed oligoclonal usage, including TCRVbeta18, which was indicated by blocking
      assay to be responsible for antigen recognition and killing. Single strand
      conformation polymorphism (SSCP) analysis revealed clonotypic bands of the
      TCRVbeta18. The PCR product of the TCRVbeta18 was sequenced and complementarity
      determining region (CDR) 3 was determined. RT-PCR analysis using this CDR3
      sequence as a primer showed, as expected, a positive band of about 30 bp smaller
      than shown on regular PCR analysis. This clonotypic PCR demonstrated an
      increasing density of PCR bands in the SART-1 PDAK cells during stimulation with
      SART-1 peptide plus DCs. It is suggested that clonotypic PCR using the TCR-CDR3
      sequence may be useful in assessing the precursor frequency of CTLs reactive with
      the SART-1 peptide in vivo.

PMID- 11956636
TI  - Recent advances in the regulation of matrix metalloproteinase 2 activation: from
      basic research to clinical implication (Review).
AB  - Matrix metalloproteinases (MMPs) play an important role in degradation of
      extracellular matrix (ECM), which is an essential step in the cascade of
      metastasis. Various types of MMPs are expressed and activated in head and neck
      squamous cell carcinoma (HNSCC) as well as other human cancers. MMP-2 is a
      prominent predictor of poor prognosis. Membrane type 1-MMP (MT1-MMP) was
      originally identified as an activator of MMP-2. In addition to the original role,
      recent studies show other important functions of MT1-MMP such as degradation of
      type I collagen and cleavage of CD44. Tissue inhibitor of MMP-2 (TIMP-2) was
      identified as an inhibitor of MMP-2 and MT1-MMP. However, TIMP-2 was reported to
      be essential for cell-mediated activation of MMP-2, and thus the contribution of
      TIMP-2 to tumor invasion has remained controversial. Some studies also suggested
      a role of TIMP-2 as a predictor of poor prognosis. Thus, inhibition of MMP
      activation by TIMPs is not a suitable strategy for suppressing invasion and
      metastasis. Instead of TIMP-2, various MMP inhibitors (MMPI) such as BB-2516 have
      been investigated with regard to suppression of tumor progression and improvement
      of prognosis in patients with advanced cancers, which resulted in no clinical
      efficacy. MMPs are especially important in the early stage of cancer progression,
      and thus strategies for future MMPI trials should be reconsidered.

PMID- 11956637
TI  - Inhibition by long-term fermented miso of induction of gastric tumors by N-methyl
      N'-nitro-N-nitrosoguanidine in CD (SD) rats.
AB  - The present study was designed to investigate the effects of fermented miso in
      the diet on the induction of gastric tumors by N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) in male CD (SD) rats. A total of 120 animals, 6 weeks of
      age, were divided into 6 groups and given MNNG (100 ppm) in the drinking water
      for 16 weeks. Starting 1 week before the carcinogen treatment the rats were fed a
      normal control MF solid diet, or the same diet containing 10% long-term
      fermented, medium- or short-term fermented miso, or 1% NaCl until the end of the
      MNNG exposure period. They were then maintained on the MF control diet and normal
      tap water until the autopsy time point at 52 weeks. The long-term fermented miso
      significantly reduced the size of the gastric tumors as compared with the other
      groups. The present results thus indicate that dietary supplementation with long
      term fermented miso could act as a chemopreventive agent for gastric
      carcinogenesis.

PMID- 11956638
TI  - Neoangiogenesis in colon cancer: correlation between vascular density, vascular
      endothelial growth factor (VEGF) and p53 protein expression.
AB  - Angiogenesis is an essential requirement for the development, progression and
      metastasis of malignant tumors. Vascular endothelial growth factor (VEGF) plays
      an essential role in the development of angiogenesis of numerous solid
      malignancies, including colon cancer. The tumor suppressor gene p53 is a potent
      transcriptional regulator of genes which are involved in many cellular
      activities, including cell-cycle arrest, apoptosis and angiogenesis. In order to
      better understand the relation among p53 status, VEGF expression and microvessels
      count (MVC) in colon cancer, we evaluated immunoreactivity for CD34 endothelium
      associated antigen, VEGF and p53 proteins in 43 cases of colon adenocarcinoma.
      Our results demonstrated an association between VEGF expression, p53 status and
      angiogenesis, suggesting that mutant p53 plays a central role in promoting
      angiogenesis in colon cancer progression.

PMID- 11956639
TI  - The influence of pre-operative radiotherapy on the expression of p53 and adhesion
      molecules: correlation with treatment results in patients with squamous cell
      carcinoma or adenocarcinoma.
AB  - E-cadherin and the catenins are responsible for inter-cellular adhesion in
      epithelial tissues. E-cadherin and/or catenin expression is often altered in
      malignancies, leading to increased invasiveness and metastatic activity of tumour
      cells. Intact adhesion molecules reduce the risk on distant metastases. This is
      confirmed by studies mostly performed on surgical series, correlating e-cadherin
      expression in tumours with prognosis and treatment outcome. It has become more
      apparent that anti-cancer treatment by itself can also affect the expression of
      adhesion molecules. We therefore suggest that the prognostic value of e-cadherin
      expression may depend on the treatment modality and the sequence of therapies
      administered for malignant tumours. We used paraffin embedded specimens from
      patients with rectal tumours and patients with laryngeal tumours treated by short
      course radiotherapy before definitive surgery. Expression of p53, e-cadherin, and
      beta-catenin was determined in pre-radiotherapy biopsies and in the surgical
      specimens. Material was available from 37 patients. We found no correlation
      between the expression of p53, e-cadherin or beta-catenin and pre-treatment
      parameters. Mutated p53 in pre-radiation biopsy correlated with increased
      occurrence of distant metastases and there was an unexpected trend for abnormal e
      cadherin expression to correlate with reduced metastases. The prognostic value of
      p53 no longer existed after examination of the surgical specimens (post
      radiotherapy). There was a trend for e-cadherin to reverse from abnormal to
      normal expression in laryngeal squamous cell carcinomas after radiotherapy, in
      5/7 cases it was accompanied with p53 conversion from positive to negative
      expression. Based on this study it is suggested that the predictive value of the
      e-cadherin expression for the occurrence of distant metastases in tumours treated
      by radiotherapy before surgery may be different from that found in tumours
      treated by surgery only. This may be related to the influence of radiotherapy on
      e-cadherin expression, especially in squamous cell carcinomas. Alteration in p53
      expression was of predictive value only in pre-treatment biopsies and the beta
      catenin status did not correlate with treatment outcome in this series.

PMID- 11956640
TI  - Carboplatin/etoposide induces remission of metastasised malignant peripheral
      nerve tumours (malignant schwannoma) refractory to first-line therapy.
AB  - Malignant peripheral nerve tumours (MPNT), e.g. malignant schwannoma, represent a
      relatively rare tumour entity which is usually regarded as a member of the group
      of soft-tissue sarcomas and treated accordingly. For chemotherapeutic approaches
      in metastasised disease, ifosfamide and doxorubicin have been identified as the
      most efficient agents, with overall response rates distinctly less than 50%. In
      case of non-response, recommendations for effective second-line regimens are
      lacking. We present the case histories of two patients with pulmonary
      metastasised MPNT that was primarily refractory to ifosfamide/doxorubicin. Both
      patients developed a partial remission with tumour reduction exceeding 50% after
      treatment with carboplatin in combination with etoposide (CE), 150 mg/m2 each,
      days 1-4 in 4-week intervals. Complete resectability of lung metastases could be
      achieved, with histologic evidence for advanced tumour regression at the time of
      resection. Patients remain in stable complete remission 20 and 28 months after
      surgery, respectively. Major CE-associated toxicity was cumulative
      myelosuppression, especially thrombocytopenia, reaching WHO grade 4. To our
      knowledge, this is the first report showing that CE is a possibly successful
      chemotherapeutic regimen in advanced MPNT, although further studies are necessary
      to evaluate its efficacy.

PMID- 11956641
TI  - Detection and quantification of SV40 large T-antigen DNA in mesothelioma tissues
      and cell lines.
AB  - SV40 viral DNA sequences, particularly large T-antigen (T-ag) DNA, have been
      reported in malignant pleural mesothelioma (MPM) and suggested to play a role in
      the tumorigenesis of this cancer. These results remain somewhat controversial
      owing to variability among a number of laboratories in reported SV40 DNA and
      protein detection in MPM tissues. This could be explained in part if SV40 DNA is
      present in relatively low abundance in many MPM tissues determined to contain
      viral sequences and is therefore difficult to detect. To this end, we
      investigated the efficacy of real time quantitative PCR in detecting low copy
      number SV40 DNA sequences, then we quantified SV40 copy number in MPM tissues and
      cell lines at our institution. Quantitative PCR demonstrated consistent precision
      and accuracy in detecting SV40 DNA sequences over a large logarithmic range of
      viral copy number. In addition, SV40 sequences were found in 2/35 tissues and 3/7
      cell lines in relatively low abundance. We conclude that SV40 is not a
      contributing factor in the pathobiology of the majority of MPM tumors from
      patients at our institution.

PMID- 11956642
TI  - Effectiveness of immunochemotherapy with PSK, a protein-bound polysaccharide, in
      colorectal cancer and changes of tumor marker.
AB  - In the present study, curatively resected patients of colorectal cancer at pTNM
      stages II and III were selected. Patients receiving postoperative combined PSK, a
      protein-bound polysaccharide, and fluoropyrimidine therapy (PSK + chemotherapy
      group) were compared with patients receiving postoperative chemotherapy alone
      (chemotherapy group) during the same period of study. Three-year disease-free
      survival rates were evaluated and the postoperative changes of serum type IV
      collagen level were investigated. The results confirmed a significant improvement
      of the three-year disease-free survival rate in the PSK + chemotherapy group
      compared to the chemotherapy group, suggesting that PSK is useful as
      postoperative prognosis control including relapse prevention for colorectal
      cancers at pTNM stage II and III. Analysis of the postoperative changes of serum
      type IV collagen level showed significantly higher levels in the chemotherapy
      group than in the PSK + chemotherapy group, and this tendency was sustained for
      12 months after surgery. This observation is speculated to be caused by
      inhibition of vascular basement membrane destruction by PSK, leading to
      inhibition of release of type IV collagen into the blood. These results indicated
      a possibility that combined PSK and chemotherapy inhibited metastasis, thereby
      reducing the risk of relapse and leading to improvement of the three-year disease
      free survival rate.

PMID- 11956643
TI  - Polymorphic CAG repeat length within the androgen receptor gene: identification
      of a subgroup of patients with increased risk of ovarian cancer.
AB  - The CAG repeat (CAGn) present in the N-terminal region of the androgen receptor
      (AR) inversely correlates with AR transactivation activity. The aim of this study
      was to investigate whether polymorphic variation in the CAGn length is associated
      with the risk of developing ovarian cancer. Using a case-control study design 121
      women with histologically confirmed ovarian cancer and 100 controls (healthy
      women) were genotyped for AR-CAG length. No marked difference in the mean length
      of CAGn was observed between ovarian cancer patients and controls. However, when
      considering patients with positive personal or family history of tumor (PPFHT),
      the mean lengths of the long allele, the short allele and the average of the 2
      alleles were longer than in the controls. Odds ratios (OR) and their
      corresponding 95% confidence intervals (CI) were computed after allowance for
      age. We observed an increase in the risk of ovarian cancer, in terms of OR, in
      women with CAGn >or=22 (OR=2.17, 95% CI:1.10-4.27). The increase of relative risk
      was particularly high in women with CAGn >or=22 belonging to the PPFHT group:
      OR=3.52 (95% CI 1.18-10.47). We also found a statistically significant trend
      (chi2 trend=4.91; p=0.03) towards an increased risk of ovarian cancer with
      increasing CAGn length (from <or=21 to 22-23, 24-25 and >or=26). Again, a strong
      association between increase in CAGn and risk of ovarian cancer was observed in
      PPFHT patients (chi2 trend=6.38; p=0.01). The results suggest that AR-CAG repeat
      length could play a role as modifier of the ovarian cancer risk conferred by
      highly penetrant genes rather than itself conferring a low risk.

PMID- 11956644
TI  - Clinical implications of urokinase and tissue type plasminogen activators and
      their inhibitor (PAI-1) in breast cancer tissue.
AB  - Cytosol of primary breast cancers from 217 women of predominantly Arab ethnicity
      were assayed for uPA, tPA, PAI-1 and a subset for ER, PR and pS2. Serum levels of
      CEA and CA153 were determined during follow-up. Only tPA correlated to nodal
      status and tumour grade, and PAI-1 to clinical stage. PAI-1 was related to uPA
      and both were inversely correlated with PR and pS2 (PAI-1 also to ER). Conversely
      tPA was directly correlated with ER, PR and pS2. Women with high tumour uPA and
      PAI-1, but not tPA, had shorter overall, and relapse-free, survival. Only nodal
      status and clinical stage were independent predictors in multivariate analysis.
      However, uPA and PAI-1 were more prognostically informative than ER or PR and
      their usefulness may extend to delineation of patients likely to respond to
      adjuvant therapy.

PMID- 11956645
TI  - CYP3A4 promoter variant is associated with prostate cancer risk in men with
      benign prostate hyperplasia.
AB  - Prostate cancer (PRCa) is one of the most common causes of cancer death in men
      and determinants of PRCa risk remain largely unidentified. Benign prostatic
      hyperplasia (BPH) is found in the majority of ageing men and has been linked with
      PRCa. CYP3A4 may influence PRCa through its role in testosterone metabolism. This
      nested case-control study assessed a CYP3A4 single nucleotide polymorphism as a
      risk factor for developing PRCa in patients with BPH. The CYP3A4 variant allele
      identified men with BPH who are at increased risk of progressing to PRCa (odds
      ratio 6.3, 95% CI 2.3-17.3), providing a potential tool to assist prediction
      strategies for this disease.

PMID- 11956646
TI  - Prevalence of hepatitis C infection in patients with non-Hodgkin's lymphomas.
AB  - Several studies have suggested an association between hepatitis C virus (HCV) and
      low-grade B-cell non-Hodgkin's lymphomas. The results, however, have been
      controversial. Italian and Japanese studies have reported a 40% prevalence rate,
      but the data were not confirmed by English and Canadian studies. We evaluated the
      prevalence of HCV infection in 109 patients with non-Hodgkin's lymphomas, and
      compared it with a control group composed of 67 patients with Hodgkin's disease
      and 31 patients with chronic lymphocytic leukemia. The prevalence of HCV
      infection was also determined in blood donors. HCV infection was detected using
      second and third generation anti-HCV ELISA. Positive results were additionally
      confirmed using Inno-LIA AbIII and/or RNA-HCV by PCR. Immunohistochemical stains
      were used to determine B or T cell lineage when the morphological analysis was
      not sufficient for lymphoma classification. HCV infection was detected in 9% of
      patients with non-Hodgkin's lymphomas, in 2% of patients in the control group
      (p=0.036), and in 1.2% of blood donors. There was no difference in the prevalence
      of HCV infection between patients with B or T cell lymphomas. Blood transfusions
      or previous surgeries, both risk factors for HCV infection, were detected in 90%
      of the patients with a positive anti-HCV test, in average 17 and 36 years before
      the diagnosis of lymphoma, respectively. Seventy percent of the patients with non
      Hodgkin's lymphomas and a positive anti-HCV test presented evidence of chronic
      liver disease when the lymphoma was diagnosed. This study suggests the presence
      of an association between HCV infection and non-Hodgkin's lymphomas in Brazil.

PMID- 11956647
TI  - Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus
      medroxyprogesterone acetate and recombinant interleukin 2 in stage IIIB-IV non
      small cell lung cancer.
AB  - The purpose of the study was to evaluate the effectiveness in terms of response
      rates, toxicity and survival of the combination chemotherapy regimen cisplatin
      and epidoxorubicin (epirubicin) including medroxyprogesterone acetate (MPA),
      recombinant IL-2 (rIL-2) and antioxidants in patients with advanced (stage IIIB
      IV) non-small cell lung cancer (NSCLC). Thirty-three chemotherapy-naive patients
      with NSCLC were enrolled in the study and 30 of them were evaluable. The mean age
      of the patients was 61 years. Twenty (66.7%) out of 30 patients were >or=60
      years, and 5 (16.7%) patients were >or=70 years. The ECOG performance status was
      0 to 1 in 30 patients and 2 in 3 patients. Twenty-six patients (78.8%) had stage
      IIIB disease and 7 (21.2%) had stage IV; histology was mainly squamous cell
      carcinoma (72.7%). The treatment consisted of cisplatin 40 mg/m2/week and
      epirubicin 40 mg/m2/week both intravenously on day 1, rIL-2 1.8 MIU/day
      subcutaneously, MPA 1 g/day orally, alpha-lipoic acid 300 mg/day orally and N
      acetyl cysteine 1.8 g/day orally. The treatment was administered for 6 weeks.
      Patients with a complete response (CR), partial response (PR) or stable disease
      (SD) continued the treatment, according to response re-evaluation, until 15
      weeks. The present study reports the results of 6, 9, 12 and 15-week treatment.
      After 6 weeks, 30 patients were assessable for response: no CR was observed, a PR
      was achieved in 15 patients (50%; ORR 50%). After 15 weeks, 1 CR and 8 PR were
      observed (ORR 30.0%). The median follow-up period was 13 months. The median
      duration of response was 9 months. The median overall survival (OS) was 15
      months. The one-year survival rate was 55.8%. The median progression-free
      survival (PFS) was 10 months. The toxicity was, as expected, mainly hematologic:
      neutropenia was the most significant symptom. The non-hematologic toxicity was
      quite low. Therefore, the treatment's toxicity was quite acceptable. There was no
      toxic death. The 30.0% ORR, the 15 month OS and the 10 month PFS obtained in this
      study are comparable with those observed with cisplatin plus epirubicin (ORR 39
      54%) in phase II studies and in a previous phase III study (ORR 33%, OS 10.5
      months). Moreover, the toxicity was acceptable and it was mainly hematologic.
      Serum levels of proinflammatory cytokines significantly decreased after
      treatment.

PMID- 11956648
TI  - The cardiovascular response in sepsis: proposed mechanisms of the beneficial
      effect of adrenomedullin and its binding protein (review).
AB  - Sepsis and its complications are leading causes of morbidity and mortality. A
      better understanding of the mechanisms responsible for the shift from the early,
      hyperdynamic phase of sepsis to the late hypodynamic phase could lead to novel
      therapies that might improve the outcome of the septic patient. Adrenomedullin is
      a vasodilatory peptide which shows sustained elevation starting early in sepsis
      and is important in initiating the hyperdynamic response. As sepsis progresses,
      however, the vascular response to adrenomedullin is blunted and this decreased
      sensitivity is important in producing the shift to the late, hypodynamic phase.
      The decline in the vascular response to adrenomedullin is related to a sepsis
      induced decrease in the binding protein for adrenomedullin (i.e., adrenomedullin
      binding protein-1) rather than a change in gene expression of the components of
      adrenomedullin receptors. Treatment of septic animals with the combination of
      adrenomedullin and its binding protein prevents the transition to the late phase
      of sepsis, maintains cardiovascular stability, and reduces sepsis-induced
      mortality. We propose that the mechanisms responsible for the beneficial effect
      of adrenomedullin and adrenomedullin binding protein-1 in sepsis are associated
      with downregulation of proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6),
      maintainence of endothelial constitutive nitric oxide synthase, and reduction of
      vascular endothelial cell apoptosis.

PMID- 11956649
TI  - Interaction of the small GTPase Rac3 with NRBP, a protein with a kinase-homology
      domain.
AB  - The family of Rac small GTPases including Rac1, Rac2 and Rac3 regulate numerous
      cellular processes. Since the cellular functions of Rac3 have not been defined,
      constitutively active V12Rac3 was used to identify targets that transduce its
      signals. We here identify human NRBP as a Rac family-interacting protein. NRBP
      formed a complex with activated Rac3. NRBP contains a kinase-homology domain and
      exhibits an associated kinase activity. NRBP represents a novel family of
      evolutionarily conserved proteins with homologs in C. elegans, D. melanogaster,
      mouse and human. Overexpression of NRBP in COS-1 cells failed to activate
      possible downstream targets of Rac3 including the JNK pathway, the p38 pathway or
      actin cytoskeletal rearrangements. Also, NRBP failed to co-localize with actin
      based stress fibers or microspikes, or with the subcortical actin. However,
      overexpression of NRBP caused a dramatic redistribution of the Golgi-associated
      marker p58 to more peripheral locations within the cell, consistent with an
      impairment of the ER to Golgi transport. Immunocytochemistry showed that NRBP and
      activated Rac3 co-localized to endomembranes and at the cell periphery in
      lamellipodia. These results suggest that NRBP functions in subcellular
      trafficking and may be directed to specific subcellular locations through
      interaction with small GTPases of the Rho family.

PMID- 11956650
TI  - Hypocrellins and Hypericin induced apoptosis in human tumor cells: a possible
      role of hydrogen peroxide.
AB  - We examined whether generation of H2O2 is a critical event for the apoptotic
      pathway upstream of mitochondrial involvement and caspase-3 protease activation.
      Perylquinone photosensitizers such as Hypocrellin A (HA), Hypocrellin B (HB) and
      Hypericin (HY) induced activation of caspase-3 and apoptosis upon
      photoactivation. Generation of H2O2 was commonly detected after photoactivation
      within an hour, and scavenging of H2O2 caused cells to fail to undergo apoptosis.
      Flow cytometry demonstrated that H2O2 production preceded loss of mitochondrial
      membrane potential (DeltaPsim) in photoactivated cells treated with HA, HB and
      HY. Then caspase-3 activity was activated, followed by DNA fragmentation. These
      findings suggest that HA, HB and HY upon photoactivation induce H2O2 generation,
      which causes (DeltaPsim) and subsequently caspase-3 activation, resulting in
      apoptosis. These findings suggest that generation of H2O2 by photoactivation of
      HA, HB and HY causes activation of caspase-3. Therefore, H2O2 may function as a
      common mediator for apoptosis induced by HA, HB and HY. The present study also
      demonstrated that upon photoactivation HA, HB and HY induced a decrease in
      intracellular acidification, glutathione (GSH) depletion and an array of
      mitochondrial damage together with apoptotic morphological changes in the
      irradiated cells.

PMID- 11956651
TI  - Distinctive gene expression of receptor-type tyrosine kinase families during rat
      hepatocarcinogenesis.
AB  - Growth factor receptor tyrosine kinase signaling plays key roles in regulating
      growth of normal hepatocytes, however, which receptor-type tyrosine kinase (RTK)
      is involved in hepatocarcinogenesis remains undetermined. The aim of this study
      was to characterize the expression of these receptors in different stages of rat
      liver carcinogenesis. We compared the expression profile of RTK genes in rat
      normal liver and diethylnitrosamine-induced hepatoma tissues using a homology
      cloning method with degenerated primers. In situ hybridization,
      immunohistochemical staining, and RT-PCR were performed to analyze the cell type
      specific expression of target RTKs during the chemically-induced
      hepatocarcinogenesis. Sequence analysis of 459 clones identified 23 different RTK
      genes. The Tie-2, c-Met, and Flk-1 genes were the most abundant RTK genes cloned
      in rat hepatoma compared to normal liver. In situ hybridization and
      immunohistochemical studies showed overexpression of c-Met and Flk-1 in GST-P
      positive preneoplastic lesions as well as neoplastic lesions. Tie-2 was expressed
      not only in endothelial cells but also in so-called oval cells, which are thought
      to be liver stem cells. Tie-2 ligand, angiopointin-1, mRNA was detected in both
      normal livers and hepatoma cells/tissues. In contrast, angiopoietin-2 mRNA was
      detected only in hepatoma tissues. These results indicate that c-Met, Tie-2 and
      Flk-1 signals play important roles in different stages of chemically-induced
      hepatocarcinogenesis. Distinctive gene expression of RTK may contribute to
      epigenic implication of hepatoma formation.

PMID- 11956652
TI  - Selective induction of apoptosis by ar-turmerone isolated from turmeric (Curcuma
      longa L) in two human leukemia cell lines, but not in human stomach cancer cell
      line.
AB  - We have investigated the effects of ar-turmerone isolated from turmeric (Curcuma
      longa L) on DNA of human leukemia cell lines, Molt 4B, HL-60 and stomach cancer
      KATO III cells. It was found that selective induction of apoptosis by ar
      turmerone was observed in human leukemia Molt 4B and HL-60 cells, but not in
      human stomach cancer KATO III cells. Morphological changes showing apoptotic
      bodies were observed in the human HL-60 and Molt 4B cells treated with ar
      turmerone. The fragmentation of DNA by ar-turmerone to oligonucleosomal-sized
      fragments that is a characteristic of apoptosis was observed to be concentration-
      and time-dependent in Molt 4B and HL-60 cells, but not in KATO III cells. The
      data of the present study show that the suppression by ar-turmerone of growth of
      these leukemia cell lines results from the induction of apoptosis by this
      compound.

PMID- 11956653
TI  - Frequent polymorphism of peroxisome proliferator activated receptor gamma gene in
      colorectal cancer containing wild-type K-ras gene.
AB  - We analyzed the K-ras gene mutation and the polymorphism of peroxisome
      proliferator activated receptor gamma (PPARgamma) gene, which is known as a
      master gene for adipocyte differentiation and a tumor suppressor gene, in
      patients with colorectal cancer by polymerase chain reaction-restriction fragment
      length polymorphism. We detected a mutation of K-ras gene at codon 12 in 8 of 39
      colorectal cancers. We also detected a polymorphism of PPARgamma gene at codon 12
      in 10 of 39 patients with colorectal cancer. Homozygous polymorphism (Ala12Ala)
      in PPARgamma gene was found only in one patient, but heterozygous polymorphism
      (Pro12Ala) was found in 9 of 29 patients. Surprisingly, all 10 colorectal cancers
      developed in the patients with polymorphism of PPARgamma gene carrying the wild
      type K-ras gene. These findings suggest that PPARgamma gene polymorphism may be
      implicated with the development of colorectal cancers, in which K-ras gene is not
      mutated.

PMID- 11956654
TI  - RelA suppresses the Wnt/beta-catenin pathway without exerting trans-acting
      transcriptional ability.
AB  - Several cellular signaling systems exhibit cross talk. Cross talk seems to play
      an important role in modifying signal effects. In vertebrates, the nuclear factor
      kappa B (NF-kappaB) signaling pathway plays important roles in immune response,
      inflammation and apoptosis. Meanwhile, the Wnt/beta-catenin signaling pathway is
      involved in oncogenesis and development. We show here that RelA, a component of
      NF-kappaB, specifically suppressed beta-catenin/Tcf-dependent transcription. This
      suppression did not depend on the trans-acting transcriptional ability of RelA.
      Furthermore, RelA neither affected the nuclear import of beta-catenin nor the DNA
      binding ability of the beta-catenin/Tcf complex, suggesting that NF-kappaB
      modifies this signaling pathway after the binding of the beta-catenin/Tcf complex
      with target DNA.

PMID- 11956655
TI  - Human adrenal cortex and aldosterone secreting adenomas express both 11beta
      hydroxysteroid dehydrogenase type 1 and type 2 genes.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 and type 2 (11betaHSD1 and 11betaHSD2)
      isozymes catalize the conversion of inactive glucocorticoids (e.g. cortisone) to
      their active forms (e.g. cortisol) and vice versa, respectively. Reverse
      transcription-polymerase chain reaction allowed the detection of 11betaHSD1 and
      11betaHSD2 mRNAs in the human adrenal cortex, liver, kidneys, as well as in six
      aldosterone-secreting adenomas. 11betaHSD1 and 11betaHSD2 activity, as evaluated
      by the capacity of the microsomal fraction to convert [3H]cortisone to
      [3H]cortisol and vice versa, was detected in both human adrenal cortex and
      aldosteronomas, although it was less elevated than in liver and kidneys.
      Aldosteronomas possessed more intense 11betaHSD1 activity and less intense
      11betaHSD2 activity than the normal adrenal cortex. The hypothesis is advanced
      that the elevated local concentration of steroid-hormone intermediates occurring
      in aldosteronomas up-regulates 11betaHSD1 and down-regulates 11betaHSD2, thereby
      contributing to their enhanced steroidogenic function.

PMID- 11956656
TI  - Elevated serum anti-carbonic anhydrase II antibodies in patients with ulcerative
      colitis.
AB  - An autoimmune mechanism has been postulated for the pathogenesis of ulcerative
      colitis (UC). The aim of this study was to evaluate the presence of anti-carbonic
      anhydrase (CA) I and anti-CA II antibodies in a series of inflammatory bowel
      disease (IBD) patients. We studied 58 IBD patients [36 UC patients and 21
      patients with Crohn's disease (CD)]. As a control, 24 healthy individuals and 12
      patients with non-IBD diarrheal diseases were tested. Serum anti-CA I and anti-CA
      II antibodies were quantified by enzyme-linked immunosorbent assay. Anti-CA II
      antibody was detected in 27.8% of UC patients, whereas anti-CA I antibody was
      detected in only 5.6% of UC patients. Positive rate of anti-CA II antibody was
      significantly higher in UC patients as compared to the control. In CD patients
      and non-IBD diarrheal patients, there were no significant increase in positive
      rate of either anti-CA I or II antibody. These results suggest that autoimmune
      responses against CA II may be involved in the pathogenesis of UC, and similar
      mechanism may participate in the development of pancreatic lesions in UC
      patients.

PMID- 11956657
TI  - Characterization of the increase in bone 66 kDa protein component with healing
      rat fractures: stimulatory effect of zinc.
AB  - The characterization of protein components produced from bone tissues with
      fracture healing was investigated. Weanling rats were sacrificed between 1 and 7
      days after the femoral fracture. Protein content in the femoral-diaphyseal
      tissues was markedly elevated by fracture healing. Moreover, when the femoral
      diaphyseal tissues with fracture healing were cultured for 24 h in a serum-free
      medium, many proteins in the bone tissues were released into the medium. Analysis
      with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed
      that many protein molecules were released from the diaphyseal tissues with
      fracture healing. Especially, a protein molecule of approximately 66 kDa was
      markedly increased by fracture healing. This protein molecule was significantly
      increased, when the diaphyseal tissues with fracture healing were cultured in the
      presence of zinc acexamate (10(-6)-10(-4) M). Zinc acexamate (10(-4) M)-induced
      increase in medium 66 kDa protein molecule was significantly inhibited in the
      presence of actinomycin D (10(-7) M) or cycloheximide (10(-6) M). The zinc effect
      was completely blocked in the presence of PD98059 (10(-5) M), an inhibitor of
      MAPK kinase, or staurosporine (10(-6) M), an inhibitor of protein kinase C. The
      medium 66 kDa protein molecule was significantly elevated in the presence of
      parathyroid hormone (1-34) (10(-7) M), insulin-like growth factor-I (10(-8) M) or
      transforming growth factor-beta (10(-11) M), while 17beta-estradiol (10(-9) M)
      did not have an effect. The effect of these bone-stimulating factors was equal to
      the zinc effect. Zinc did not significantly enhance the effect of insulin-like
      growth factor-I in increasing medium 66 kDa protein molecule. The present study
      demonstrates that fracture healing increases production of the approximately 66
      kDa protein molecule which is a major component produced from femoral-diaphyseal
      tissues of weanling rats, and that this elevation is enhanced by zinc treatment.

PMID- 11956658
TI  - Expression of human GIPC1 in normal tissues, cancer cell lines, and primary
      tumors.
AB  - GIPC1/RGS19IP1/GIPC, GIPC2, and GIPC3 are a family of central PDZ-domain proteins
      with GH1 and GH2 domains. GIPC1 interacts with GTPase-activating protein
      RGS19/RGS-GAIP, TGFbeta type III receptor, receptor tyrosine kinase TrkA, and
      integrin alpha6A subunit. Xenopus homologue of human GIPCs interacts with
      Frizzled-3 class of WNT receptor. We investigated expression of human GIPC1 mRNA
      in normal tissues, cancer cell lines, and primary tumors. GIP1A probe (nucleotide
      position 1075-1483 of GIPC1 cDNA) hybridized to GIPC1 mRNA of 1.8 kb in size.
      GIPC1 mRNA was almost ubiquitously expressed in various normal tissues.
      Expression level of GIPC1 mRNA was relatively lower in bone marrow and peripheral
      blood leukocytes. GIPC1 mRNA was relatively highly expressed in gastric cancer
      cell lines OKAJIMA, TMK1, MKN28, MKN45, MKN74, KATO-III, pancreatic cancer cell
      line AsPC-1, colorectal cancer cell line SW480, and lung cancer cell line A549.
      On the other hand, GIPC1 mRNA was almost undetectable in leukemia/lymphoma cell
      lines HL-60, Raji, and Daudi. Expression of GIPC1 mRNA was down-regulated in 12
      out of 14 cases of primary kidney tumors, 10 out of 18 cases of primary
      colorectal tumors, 3 out of 8 cases of primary gastric cancer, 3 out of 3 cases
      of primary prostate cancer. Because GIPC1 induces increased expression of TGFbeta
      type III receptor at the cell surface and enhanced responsiveness to TGFbeta,
      down-regulation of GIPC1 mRNA in tumors might promote cellular proliferation
      through interference of TGFbeta signaling.

PMID- 11956659
TI  - Frequent up-regulation of WNT5A mRNA in primary gastric cancer.
AB  - WNT signal is transduced to the beta-catenin - TCF pathway, the JNK pathway, or
      the Ca2+-releasing pathway through seven-transmembrane-type WNT receptors encoded
      by Frizzled genes (FZD1-FZD10). We have previously cloned and characterized human
      WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B,
      WNT11, WNT14, and WNT14B/WNT15 by using bioinformatics, cDNA-library screening,
      and cDNA-PCR. Here, we investigated expression of human WNT5A mRNA in various
      normal tissues, 66 primary tumors derived from various tissues, and 15 human
      cancer cell lines. WNT5A mRNA was relatively highly expressed in salivary gland,
      bladder, uterus, placenta, and fetal kidney. Up-regulation of WNT5A mRNA was
      detected in 5 out of 8 cases of primary gastric cancer, 5 out of 18 cases of
      primary colorectal tumors, and in 2 out of 7 cases of primary uterus tumors by
      using matched tumor/normal expression array analysis. Up-regulation of WNT5A mRNA
      was also detected in 7 out of 10 other cases of primary gastric cancer by using
      cDNA-PCR. Although low-level expression of WNT5A mRNA was detected in gastric
      cancer cell line MKN45, WNT5A mRNA was almost undetectable in gastric cancer cell
      lines OKAJIMA, TMK1, MKN7, MKN28, MKN74, and KATO-III. Compared with frequent up
      regulation of WNT5A mRNA in primary gastric cancer, expression levels of WNT5A
      mRNA in 7 gastric cancer cell lines were significantly lower than that in normal
      stomach. Frequent up-regulation of WNT5A mRNA in human primary gastric cancer
      might be due to cancer-stromal interaction.

PMID- 11956660
TI  - Histone deacetylase inhibitors sensitize human colonic adenocarcinoma cell lines
      to TNF-related apoptosis inducing ligand-mediated apoptosis.
AB  - Histone deacetylase inhibitor (HDAI) induces accumulation of highly acetylated
      histones by inhibiting the activity of histone deacetylase and inhibits cell
      proliferation, induces differentiation, and promotes apoptosis. TNF-related
      apoptosis inducing ligand (TRAIL) induces apoptosis in various human cancer
      cells, a promising observation because it raises the possibility of a death
      ligand selectively for tumor cells. However, resistance to TRAIL-induced
      apoptosis was seen in colonic adenocarcinoma cell lines. So we investigated
      whether human colonic adenocarcinoma cell lines can be sensitized to TRAIL
      induced apoptosis by the addition of HDAI. We investigated sensitivity to histone
      deacetylase inhibitor in colonic adenocarcinoma cell lines using the MTT assay.
      Cell viability decreased with sodium butyrate (SB) and trichostatinA (TSA) in a
      dose-dependent manner in LS 180 and HT-29 cells. Nuclear condensation and
      fragmentation were observed by DAPI staining after 24 h stimulation with SB or
      TSA in LS 180 cells. We also investigated the combination of HDAI and TNF family
      members (TRAIL, anti-Fas antibody or TNFalpha) in colonic adenocarcinoma cell
      lines. HDAI augmented TNF family-related apoptosis in LS 180 cells and HT-29
      cells. HDAI sensitizes human colonic adenocarcinoma cell lines to TRAIL-mediated
      apoptosis. HDAI may be useful as an adjuvant agent for TRAIL in the treatment of
      human colonic adenocarcinomas that are resistant to TRAIL.

PMID- 11956661
TI  - Insulinotropic action of amino acids at their physiological concentrations: I.
      Experiments in incubated islets.
AB  - In order to simulate physiological conditions, the influence of a mixture of 22
      amino acids together with taurine, all tested at their normal concentration in
      plasma, upon insulin release, D-glucose metabolism and (45)Ca net uptake was
      investigated in isolated rat pancreatic islets. The amino acid mixture had little
      effect upon insulin release at low concentrations of D-glucose but augmented, by
      up to 50%, the release of insulin provoked by higher concentrations of D-glucose.
      The effects of glibenclamide, forskolin, theophylline and cytochalasin B upon
      insulin release evoked by D-glucose in the absence or presence of the amino acid
      mixture and the changes in insulin output evoked by the omission from the amino
      mixture or addition to media containing only D-glucose of selected amino acid(s),
      as well as the influence of the amino acid mixture upon D-glucose metabolism and
      (45)Ca net uptake, were considered as compatible with both the role of certain
      amino acids as nutrients and the accumulation of other amino acids as positively
      charged molecules in the islet cells.

PMID- 11956662
TI  - General survey of intertumor linkages that connect the chronological changes of
      age-adjusted incidence rates of 13 neoplasia types from l975 to l993 in Japan.
AB  - We attempted a stochastic study of cancer risk change in time using the follow-up
      data of the age-adjusted incidence rate (AAIR) of cancer in Japan, which covered
      13 neoplasia types of both sexes in scope, and ranged from 1975 to 1993 in time.
      The purpose of our study was to test whether or not there was any mathematical
      regularity that was to condition cancer risk changes in time in all the 13 human
      neoplasia types. We investigated the relation between 2 neoplasias as regards log
      AAIR changes in time by the direct successive elimination method of Gauss, a
      fitness test of a given pair data to an equilibrium model. The fitness test was
      repeated in each of 156 tumor pairs [P(13.2)] in both sexes, in each of 3 (x, y)
      coordinates - the original (x, y) coordinates, the rect- (x, y) coordinates and
      the para- (x, y) coordinates. Total number of fitness test in this study was
      estimated to be 156x2x3=936. The rect- (x, y) coordinates and the para- (x, y)
      coordinates were defined each as an (x, y) framework with its x axis crossed at a
      right angle to the regression line of the original log AAIR data, and as another
      framework with its x axis run in parallel with the regression line of the
      original log AAIR data. The fitness of a given tumor to an equilibrium system was
      assessed in terms of the correlation coefficient value r within the range of 
      1.000 (the oncogene-type equilibrium system) to +1.000 (the tumor suppressor gene
      type equilibrium system). Results obtained are given as follows: i) the
      positivity rates of the fitness test to the oncogene-type equilibrium system and
      the tumor suppressor gene-type system in the male all-cancer population were each
      95.5% (149/156 tumor pairs) and 79.5% (124/156 tumor pairs), and those in the
      female all-cancer population were each 91.0% (142/156 tumor pairs) and 83.3%
      (130/156 tumor pairs). Evidence was available to indicate that all of the 13
      human neoplasia types of both sexes was associated with both oncogene activation
      and tumor suppressor gene inactivation at the level of individual tumors. In
      other words, clearance of both oncogene activation and tumor suppressor gene
      inactivation was the sine qua non premise of carcinogenesis. ii) The positivity
      score profiles of a given tumor (profile-like presentation of positivity score
      for each tumor), for each of 2 cancer genes and for each sex, was highly specific
      for each of the 26 tumor units (13 tumors of both sexes). The presence of a
      highly specific positivity score pattern might be taken as another expression of
      complex interaction of 2 cancer genes in carcinogenesis. iii) Evidence was
      presented to suggest that specified interactions of the oncogene-tumor suppressor
      gene complexes of both sexes might be causally related to the emergence of sex
      discrimination of cancer risk, as testified in a set of tumors with both male
      dominance of cancer risk and female dominance of cancer risk. iv) The
      significance of one tumor pair that failed to show fitness to both the oncogene
      type equilibrium system and the tumor suppressor gene-type equilibrium system was
      discussed in terms of spacially restricted dissociation of the power center of
      the oncogene-type equilibrium system from that of the tumor suppressor gene-type
      equilibrium system in a given tumor pair.

PMID- 11956663
TI  - Molecular profiling of high-risk neuroblastoma by cDNA array.
AB  - The aim of this study was to investigate gene expression changes in disseminated
      neuroblastoma by cDNA array technique. Three stage IV neuroblastomas and one
      neuroblastoma cell line (SK-N-FI) were analyzed. Expression profiles were
      confirmed by semiquantitative RT-PCR and in some instances by Northern blotting.
      Comparison of expression profiles identified several genes which were highly
      expressed as well as some which were down-regulated in tumor samples relatively
      to SK-N-FI cells. The tumors studied lacked N-myc overexpression, while showing
      up-regulation of basic transcription factors, growth factors and receptors such
      as NSEP, c-myc binding protein MM1, thymosin beta10 (TMSB10), TNF-R superfamily
      member 10A (TNFRSF10A) and FZ9. These results suggest that cDNA array technology
      is a powerful tool to identify a set of genes involved in neuroblastoma genesis
      and progression. Thus, the sensitive cDNA array may provide new insight into many
      aspects of pediatric tumors and play crucial role in the administration of
      adjuvant therapy of patients with neuroblastoma.

PMID- 11956664
TI  - Overexpression of v-myb oncogene or c-myb proto-oncogene in insect cells:
      characterization of newly induced nucleolus-like structures accumulating Myb
      protein.
AB  - The oncoprotein v-Myb induces myeloid leukemia and its cellular counterpart c-Myb
      is involved in the regulation of hematopoiesis. Although intensively studied,
      their precise subcellular localization is not known. In order to expand our
      knowledge in this respect, we used an artificial system overexpressing these
      proteins. We investigated the subcellular localization of Myb proteins in
      cultured non-synchronized insect cells transfected with recombinant baculoviruses
      overexpressing either v-myb oncogene or c-myb proto-oncogene. The cell expressing
      Myb proteins underwent extensive nuclear changes and exhibited distinct nuclear
      structures resembling nucleoli. The bulk of v-Myb and c-Myb proteins accumulated
      in such nucleolus-like structures which, according to the nucleolar nomenclature,
      we classified to three types: compact of enlarged size (type I), large ring
      shaped (type II) and with nucleolonemas (type III). We investigated these
      structures for the presence of important nucleolar macromolecules in order to
      establish whether they were compatible with the function in the production of
      ribosomes. Strikingly, our results indicated that the different forms of these
      structures did not represent genuine nucleoli. They rather reflected progressive
      changes, induced by the virus infection and high expression of v-myb genes,
      accompanied by the formation of these prominent nucleolus-like structures highly
      enriched in Myb protein. Gradual changes in number of individual nucleolus-like
      forms during infection, increasing amount of Myb protein and DNA localized in
      them together with decreasing amount of RNA and their different interaction with
      viral particles indicate that the nucleolus-like structure of type I is a
      precursor of the type II and finally of the type III.

PMID- 11956666
TI  - No vasodilator response to low-dose heparin in the forearm skeletal-muscle
      vascular bed.
AB  - OBJECTIVE: Recent reports show that heparin induces vasodilation. This heparin
      induced vasodilation might interfere with the results of vascular studies using
      the perfused-forearm technique because the arterial catheter is often flushed
      with a heparin solution in those experiments. Therefore, we investigated the
      vascular effects of flushing an arterial catheter with a heparin solution
      compared with a placebo solution (NaCl 0.9%) in six healthy volunteers. METHODS:
      During the first half of each experiment, the arterial catheter was flushed
      several times with the placebo solution. In the second half, identical flushes
      were performed with a solution of heparin diluted in NaCl 0.9% (4U x ml(-1)).
      RESULTS: Forearm blood flow (venous occlusion plethysmography) response was
      similar with heparin and placebo after all flushes. CONCLUSION: We conclude that
      low-dose heparin in the solution to flush an arterial catheter has no short-term
      vasodilator effect in the human forearm vascular bed. Therefore, the results of
      studies using the perfused-forearm technique are not confounded by flushes with a
      low-dose heparin solution.

PMID- 11956665
TI  - The effects of folate supplementation on some coagulation parameters and
      oxidative status surrogates.
AB  - OBJECTIVE: To determine whether folate treatment, besides decreasing homocysteine
      (tHcy), improves coagulation status, oxidative stress and endothelial dysfunction
      and whether these depend on genetic polymorphism of the enzyme
      methylenetetrahydrofolate reductase (MTHFR). METHODS: Fifty-seven volunteers
      (males 30, females 27, mean age 61.2 years) with high coronary risk or manifest
      atherosclerotic disease and tHcy concentration of at least 20 micro mol/l
      participated in an open, prospective study - 1 month of placebo period, followed
      by 2 months of treatment with folate 10 mg daily. Concentrations of tHcy were
      measured using high-pressure liquid chromatography with fluorescence detection.
      Other variables were measured using commercial kits, and polymorphism of MTHFR
      was detected using a polymerase chain reaction. RESULTS: Folate treatment
      resulted in a significant decrease of tHcy and fibrinogen, while plasminogen and
      antithrombin III significantly increased. Glutathione peroxidase, glutathione and
      superoxide dismutase significantly increased after the folate treatment;
      moreover, malonyldialdehyde and von Willebrand factor decreased concomitantly.
      The individual MTHFR polymorphism did not influence the outcomes of folate
      treatment. CONCLUSION: Folate treatment resulted not only in tHcy decrease, but
      also in an improvement of hypercoagulation, oxidative stress and endothelial
      dysfunction. The sufficiently high dose of folate seems to be able to decrease
      plasma tHcy in all three individual MTHFR polymorphism groups, to almost the same
      post-treatment concentrations.

PMID- 11956667
TI  - Effect of a conserved mutation in uridine diphosphate glucuronosyltransferase 1A1
      and 1A6 on glucuronidation of a metabolite of flutamide.
AB  - OBJECTIVE: We investigated how the conserved mutation (Y486D) changed the kinetic
      parameters of uridine diphosphate glucuronosyltransferase 1A1 and 1A6 (UGT1A1 and
      1A6) for 2-amino-5-nitro-4-trifluoromethylphenol, which is a major metabolite of
      flutamide, a nonsteroidal antiandrogenic agent. METHODS: The wild-type or mutant
      cDNA-expressed UGT was co-incubated with 2-amino-5-nitro-4-trifluoromethylphenol
      (aglycone) and uridine diphosphate-glucuronic acid (UDP-GA, donor substrate). The
      glucuronidation of the aglycone was determined. RESULTS: The maximum velocities
      of the mutant UGT1A1 and UGT1A6 were about 12% and less than 1% of the
      corresponding wild-type, respectively. The Michaelis constant (K(M)) for the
      aglycone of the wild-type UGT1A1 was double that of the mutant, but the K(M) for
      UDP-GA of the wild-type UGT1A1 was not significantly different from that of the
      mutant. CONCLUSION: Patients with Y486D may accumulate excessive 2-amino-5-nitro
      4-trifluoromethylphenol, which might lead to unexpected toxicity.

PMID- 11956668
TI  - CYP2C19 genotype and S-mephenytoin 4'-hydroxylation phenotype in a Chinese Dai
      population.
AB  - AIMS: To investigate the incidence of the CYP2C19 polymorphism in the Chinese Dai
      population. METHODS: One hundred and ninety-three healthy Chinese Dai volunteers
      were identified with respect to CYP2C19 by genotype and phenotype analyses. A
      polymerase chain reaction-restriction fragment length polymorphism method was
      performed for genotyping procedures. The 4'-hydroxymephenytoin (4'-OH-MP) and S/R
      mephenytoin ( S/R-MP) excreted in the urine were determined by high-performance
      liquid chromatography and gas chromatography, respectively. RESULTS: Eighteen
      subjects were identified as poor metabolisers (PMs). The frequency of PMs in the
      Chinese Dai subjects was 9.3% (95% confidence interval 5.2, 13.4), which is lower
      than that in the Chinese Han population ( P<0.05). Chinese Dai subjects had a
      higher frequency of the mutant CYP2C19*2 allele (0.303) and a lower frequency of
      the mutant CYP2C19*3 allele (0.034). These two mutant alleles could explain all
      deficiencies of CYP2C19 activity in the Chinese Dai subjects. The frequency of
      the CYP2C19*3 allele is significantly lower than that in the Chinese Han
      population ( P<0.05). The mean S/R ratio was lower in the homozygous extensive
      metabolisers (EMs) compared with that in heterozygous EMs ( P<0.01), and the
      latter was lower than that in the PMs ( P<0.01). Furthermore, the mean S/R ratio
      in CYP2C19*3/ CYP2C19*2 heterozygous PMs was possibly lower than that in the
      CYP2C19*2/ CYP2C19*2 homozygous PMs ( P<0.05). CONCLUSION: The frequencies of PMs
      and CYP2C19*3 allele in the Chinese Dai population are significantly lower than
      those in the Han population. The CYP2C19 genotype analysis is largely consistent
      with the mephenytoin phenotype analysis. The variability of S/R ratios in EMs and
      PMs shows a gene-dosage effect.

PMID- 11956669
TI  - Time-dependent pharmacokinetics and drug metabolism of atovaquone plus proguanil
      (Malarone) when taken as chemoprophylaxis.
AB  - OBJECTIVE: To determine the pharmacokinetic profiles of atovaquone (ATO),
      proguanil (PROG) and its active metabolite cycloguanil (CYCLO) with respect to
      possible accumulation and kinetic interaction upon repeated dosing with Malarone.
      METHODS: Thirteen healthy volunteers first received a single dose and then after
      1 week, repetitive daily doses of Malarone (one tablet) for 13 days. For analysis
      of plasma drug concentrations, blood samples were collected at regular intervals
      over 8 days after a single dose and over 12 days after the last day of multiple
      dosing. Single-dose and steady-state pharmacokinetic parameters were determined
      for each individual. Genotyping of the gene coding for CYP2C19, a major enzyme
      catalyzing PROG metabolism, was performed using polymerase chain reaction, and in
      vitro enzyme kinetic experiments were carried out to study the possible effect of
      ATO on the catalytic activities of CYP2C19 and 3A4 using fluorometric assays.
      RESULTS: For ATO, the ratio of the area under the concentration-time curve (AUC)
      during the last dose interval to the AUC after the single dose (AUC(0- tau)/AUC(0
      infinity)) was found to be 0.90 [95% confidence interval (CI) 0.56, 1.24]
      indicating absence of undue accumulation. AUC(0- tau), and peak plasma
      concentration at steady state (C(max,ss)) values were, however, threefold lower
      than those reported in human immunodeficiency virus-infected subjects after 12
      multiple daily doses of 250 mg ATO alone. Four volunteers, with mean CYCLO/PROG
      AUC(0-tau) of 0.03 (-0.23, 0.09) were classified as poor metaboliser (PM)
      phenotypes. There was a significant increase in the AUC of PROG at steady state
      with a PROG AUC(0-tau)/AUC(0-infinity) ratio of 1.38 (1.07, 1.69) in extensive
      metaboliser (EM) phenotypes. CYCLO/PROG AUC ratios were significantly lower 0.67
      (0.54, 0.81) at steady state than that after the first single dose in EM
      phenotypes. The in vitro kinetic experiments on recombinant enzymes (CYP2C19 and
      CYP3A4) suggested a possible inhibition of catalytic activity of CYP3A4 by ATO.
      CONCLUSIONS: There was no unexpected accumulation of ATO following repeated
      administrations of the combination. In EM phenotypes, PROG elimination was
      reduced at steady state. Also, at steady state, either the elimination of CYCLO
      was increased or its formation clearance decreased the latter possibly by
      inhibition of CYP3A4 by ATO.

PMID- 11956670
TI  - Allele and genotype frequencies of polymorphic DCP1, CETP, ADRB2, and HTR2A in
      the Egyptian population.
AB  - OBJECTIVE: The goal of this study was to determine the frequencies of important
      allelic variants of two drug targets, dipeptidyl carboxypeptidase ( DCP1) and
      cholesteryl ester transfer protein ( CETP), and two other drug receptors, beta-2
      adrenergic receptor ( ADRB2) and 5-hydroxy tryptamine 2A receptor ( HTR2A), in
      the Egyptian population and compare them with the frequencies in other ethnic
      populations. METHODS: A sensitive real-time polymerase chain reaction assay was
      developed and successfully applied for genotyping of the consensus (wild-type)
      alleles plus five variants of four genes: DCP1 [the insertion allele ( I) versus
      the deletion allele ( D)], CETP*TaqI ( B1 versus B2), ADRB2*R16G, ADRB2*Q27E, and
      HTR2A*102T>C. This study was carried out in 242 unrelated Egyptian subjects and
      is the first to describe these allelic variants in the Egyptian population.
      RESULTS: The frequencies of the tested alleles were found as: DCP1 ( I: D,
      0.32:0.68), CETPTaqI ( B1: B2, 0.65:0.35), ADRB2*R16G ( Arg16: Gly16, 0.57:0.43),
      ADRB2*Q27E ( Gln27: Glu27, 0.76:0.24), and HTR2A*102T>C ( T102: C102, 0.53:0.47).
      The common Arabian ancestors of the Egyptians, Spanish, Saudi, and Emirate had
      created a common pattern of distribution of some allelic variants ( DCP1 and
      CETP). However, in the genotyping of ADRB2, the frequency of the polymorphism at
      codon 16 was found to be similar to the Chinese population, whereas that at codon
      27 was similar to African-Americans with significant differences than other
      Caucasian populations. The frequency of the HTR2A*102T>C variant appeared to be
      similar to many Caucasian populations and African-Americans. CONCLUSIONS: We have
      explored the frequencies of important allelic variants DCP1, CETP, ADRB2, and
      HTR2A among the Egyptian population focusing on the ethnic diversity in the
      distribution of the tested mutant alleles. Our results may help in better
      understanding the observed ethnic variation in angiotensin-converting enzyme
      inhibition and atherosclerosis therapy. It also may contribute to better
      characterization of interethnic differences in isoprenaline and clozapine
      response, which will have implications for the cost effective and rational
      prescribing of these drugs.

PMID- 11956671
TI  - Protein binding of ketamine and its active metabolites to human serum.
AB  - Ketamine is an anaesthetic agent extensively used in intensive care patients, and
      it has proved its efficacy in the management of burned patients. In these
      patients, alterations in serum protein binding occur that may have significant
      clinical implications. Scarce data were observed in the literature about the
      binding of ketamine to human plasma proteins, and no data about the binding of
      its active metabolites, norketamine (NK) and dehydronorketamine (DHNK) were
      found. In this study, protein binding of ketamine, NK and DHNK in human serum
      were determined using the ultrafiltration technique. The percentage of drug bound
      to serum proteins at 30 degrees C was found to be 69%, 60% and 50% for DHNK,
      ketamine and NK, respectively, while these percentages were 75%, 64% and 54% for
      DHNK, ketamine and NK respectively at 20 degrees C. The binding of ketamine and
      its metabolites was independent of drug concentration.

PMID- 11956672
TI  - Determination of thiopurine S-methyltransferase phenotype using thin-layer
      chromatography and quantitative scanning.
AB  - OBJECTIVE: To develop a non-high-performance liquid chromatography method for the
      determination of thiopurine- S-methyltransferase (TPMT) phenotype using thin
      layer chromatography and quantitative scanning. METHODS: TPMT reaction was
      performed using a radiochemical assay. The reaction product [(14)C]-6
      methylmercaptopurine was separated using thin-layer chromatography and quantified
      by means of radioactive scanning. Day-to-day variance was determined to validate
      results. RESULTS: Determination of TPMT phenotype using thin-layer chromatography
      and quantitative scanning is reliable (day-to-day variance 8.5+/-1.7%, mean+/
      SEM). Mean TPMT activity in 314 randomly selected patient samples was 11.8+/-3.3
      units/ml red blood cells (mean+/-SD, range 3.5-25 units/ml). CONCLUSION: We
      developed a new assay variant for the determination of TPMT phenotype that is
      easy to perform, reliable and reduces production of radioactive waste. This may
      lead to more frequent pretreatment determination of TPMT phenotype and increase
      drug safety and efficacy by individualising thiopurine doses.

PMID- 11956673
TI  - Effects of grapefruit juice and smoking on verapamil concentrations in steady
      state.
AB  - OBJECTIVE: Human gut wall cytochrome P(450) (CYP)3A4 is inhibited by grapefruit
      juice (G), whereas smoking increases CYP1A2 activity. Both enzymes contribute to
      verapamil biotransformation. This study was performed to quantitatively assess
      the effect of these factors on verapamil pharmacokinetics in steady state.
      METHODS: Twenty-four young healthy volunteers of both sexes (12 smokers, 12 non
      smokers) participated in this randomised crossover study. Prolonged release
      verapamil (120 mg, Isoptin KHK) was given bid for 7 days in two periods. During
      days 5-7, 1 l of either G or water was coadministered daily. On day 7,
      concentrations of verapamil and norverapamil enantiomers were determined during
      one dosing interval, and model independent pharmacokinetic parameters were
      estimated. PR intervals were monitored for pharmacodynamics. Statistical
      evaluation was done essentially using bioequivalence methods. RESULTS: G
      significantly increased ( R, S)-verapamil the area under the concentration-time
      curve at steady state (AUC(tau,ss)) by a mean of 1.45-fold [90% confidence
      interval (CI) 1.29, 1.63] and peak plasma concentration at steady state
      (C(max,ss)) by 1.63-fold (90% CI 1.38, 1.91). The increase in concentrations
      present for ( R)- and ( S)-enantiomers was slightly greater for verapamil than
      for norverapamil. Smokers had significantly lower AUC(tau,ss) and C(max,ss)
      values than non-smokers by (means) 0.61-fold to 0.85-fold for verapamil and
      norverapamil enantiomers, respectively. G effects were unrelated to naringenin
      pharmacokinetics. Prolongation of PR intervals by G coadministration was
      borderline significant; an increase above 350 ms occurred in two individuals
      during the G period. Significantly increased urinary 6-beta-hydroxycortisol
      excretion by G suggests induction of hepatic CYP3A. CONCLUSIONS: Patients on
      verapamil treatment should abstain from grapefruit juice. Smoking habits should
      be considered for verapamil dosing.

PMID- 11956674
TI  - Use of anti-asthmatic drugs in Italy: analysis of prescriptions in general
      practice in the light of guidelines for asthma treatment.
AB  - Our aim was to analyse anti-asthmatic drug utilisation in primary health care in
      a Northern Italian region in the light of guidelines for asthma treatment.
      METHODS: We collected all prescriptions for anti-asthmatic agents reimbursed in
      1998 in six local health authorities (overall population: 1,909,192 inhabitants)
      of Emilia Romagna (Northern Italy). The asthmatic cohort was defined as the
      population of subjects aged 20-44 years receiving at least one prescription of an
      anti-asthmatic agent devoid of indications for transient respiratory diseases. In
      order to include routine users, the asthmatic cohort was restricted to those
      subjects with at least one prescription in the first quarter of 1998. Anti
      asthmatic agents were classified according to their therapeutic role as follows:
      maintenance therapy for mild-moderate asthma (Mm); maintenance therapy for severe
      asthma (Ms); quick relief for mild attack (Qm) and quick relief for severe attack
      (Qs). RESULTS: The asthmatic cohort included 11,518 subjects; of these, 47%
      received only one prescription in 1998. The most frequent regimens were Mm+Qm
      (25%) and Qm alone (23%). Some regimens appeared not to be in accordance with
      international recommendations. The main reasons were lack of drugs for quick
      relief (36%), use of long-term beta(2)-adrenoceptor agonists (Ms drugs) without
      quick-relief or anti-inflammatory agents (10% of the cohort and 56% of the
      recipients of Ms drugs) and presence of fixed-dose combinations (27%). In 76% of
      the patients treated with Mm drugs (mainly inhaled steroids), the total amount of
      drugs prescribed over the 1-year period covered less than 150 days. CONCLUSIONS:
      The use of anti-asthmatic drugs in general practice in Italy does not seem to
      comply with the international recommendations especially with regard to the use
      of quick-relief agents. Active interventions to implement guidelines and monitor
      the choice of drug regimens are warranted.

PMID- 11956675
TI  - Use of unconventional medicine in Italy: a nation-wide survey.
AB  - OBJECTIVE: To investigate the prevalence of use of unconventional therapies in
      Italy, the main health problems associated with and the motivations for use of
      these therapies. METHODS: Questions about the use of unconventional therapies
      were inserted in a nation-wide survey conducted by face-to-face interviews with
      all members of sampled families by the National Institute of Statistics during
      four quarters of the years 1999-2000. Data presented here are based on the
      results of the first two quarters of the survey (September and December 1999)
      during which a representative sample of 30,000 Italian families (70,898
      individuals) was interviewed. RESULTS: Almost 9 million people (15.6% of the
      Italian population) used at least one unconventional therapy during the period
      1997-1999. Homeopathy was the most frequently used (8.2% of the population),
      followed by manual treatments (7%), herbal medicine (4.8%) and acupuncture
      (2.9%). Homeopathy was also quite commonly used by children (7.7% of Italian
      children). The main reason for use was concern about potential toxicity of
      "conventional medicine". The health problem most frequently treated with all
      kinds of unconventional therapies was pain. CONCLUSIONS: Use of unconventional
      therapies has almost doubled since 1991. However, with 15.6% of the Italian
      population (9 million people) using at least one therapy, Italy ranks among the
      "light" users compared with other European countries. Homeopathy is the most
      frequently used therapy. The typical user is, as in other western countries, a
      highly educated woman aged 35-44 years and resident in the richest part of the
      country (north-eastern Italy).

PMID- 11956676
TI  - Knowledge on drug dosages of ward physicians.
AB  - OBJECTIVE: Dosing errors are a common source for preventable adverse drug events.
      This study evaluated the knowledge of German hospital physicians with respect to
      the daily dosage of frequently used drugs. METHODS: A questionnaire survey was
      carried out among 168 ward physicians from three university and four municipal
      hospital departments of internal medicine asking for the daily dosage of 17
      frequently used drugs. RESULTS: One hundred twenty-seven of 168 physicians
      returned a completed questionnaire, a response rate of 75.6%. Only 50% of the
      dose estimates were within the therapeutic range. Even in cases of frequent
      prescription 7% of the stated doses were overdosed and 15% were underdosed.
      CONCLUSIONS: The results of this survey suggest that adverse drug events and the
      lack of therapeutic effect due to dosing errors could be prevented by an improved
      knowledge of daily dosages.

PMID- 11956677
TI  - Inhibition by atovaquone of CYP2C9-mediated sulphamethoxazole hydroxylamine
      formation.
AB  - OBJECTIVE: To determine whether the antiprotozoal drug atovaquone inhibits the
      cytochrome P(450) (CYP)2C9-mediated metabolism of sulphamethoxazole (SMX) to its
      potentially harmful hydroxylamine metabolite (SMX-HA) in vitro. METHODS:
      Generation of SMX-HA from SMX was measured directly using high-performance liquid
      chromatography in human liver microsomes or expressed CYP2C9*1, with or without
      preincubation with reduced nicotinamide adenine dinucleotide phosphate, and the
      inhibition constant (K(i)) for atovaquone was determined. To determine the effect
      of protein binding in vitro, in some experiments, atovaquone was pre-incubated
      with serum proteins, followed by filtration. RESULTS: The K(i) for inhibition of
      SMX-HA formation by atovaquone was 15 microM, which is within clinically
      attainable total plasma atovaquone concentrations of 45-55 microM. Atovaquone (45
      microM) inhibited SMX-HA formation by 39% in human liver microsomes. However,
      following preincubation of atovaquone with serum proteins, no inhibitory effect
      by atovaquone was observed, consistent with previous reports of high plasma
      protein binding for atovaquone. Compared with human liver microsomes, CYP2C9*1
      showed an eightfold greater specific activity for SMX-HA generation; as for liver
      microsomes, CYP2C9*1 activity was inhibited by atovaquone. CONCLUSIONS:
      Atovaquone is a relatively weak inhibitor of CYP2C9-mediated SMX-HA formation in
      vitro. However, the effect is not observed in the presence of serum proteins. It
      is therefore unlikely that atovaquone would significantly inhibit SMX-HA
      formation in vivo.

PMID- 11956678
TI  - The use of analgesic drugs in postoperative patients: the neglected problem of
      pain control in intensive care units. An observational, prospective, multicenter
      study in 128 Italian intensive care units.
AB  - OBJECTIVE: The use of analgesic drugs in patients admitted to Italian intensive
      care units (ICUs) was assessed. METHODS: An observational, prospective, cohort
      study was conducted, involving all adult patients admitted during a 1-month
      period in 128 Italian general ICUs. The use of analgesic drugs was evaluated for
      the first 2 postoperative days in surgical patients who stayed in ICU for at
      least 2 days. RESULTS: We observed 661 postoperative patients who underwent
      elective (72%) or emergency surgery. Of the patients with an ICU stay of at least
      2 days, 49% did not receive any opioids in the first 48 postoperative hours, and
      more than 35% did not receive any analgesic at all. The most used opioid was
      fentanyl, followed by morphine and buprenorphine. Among the 336 patients who
      received at least one opioid, as many as 42% had only a single bolus per day.
      Pain control was reported as the reason for drug use in 54.5% of opioid
      administrations, while control of anxiety covered 10.3% of them. The probability
      of receiving an opioid was lower for patients in coma. CONCLUSION: Management of
      postoperative pain in Italian ICUs was insufficient, particularly in
      neurosurgical and comatose patients. A general lack of knowledge about pain and
      misconceptions about pain drugs may be at the basis of these results.

PMID- 11956679
TI  - Availability of drugs to admitted patients in Yemeni public hospitals.

PMID- 11956682
TI  - Identifying a folding nucleus for the lysozyme/alpha-lactalbumin family from
      sequence conservation clusters.
AB  - Four subfamilies of c-type lysozyme and one subfamily of alpha-lactalbumin are
      defined from 78 sequences, and their folding nucleus is identified with a method
      based on conserved residues and native structural contacts between pairs of
      conserved residues. One large cluster of 19 conserved residues is found which is
      mostly nonpolar, buried, and nonfunctional. It can be subdivided into three
      subclusters: (1) conserved residues in four helices; (2) conserved residues that
      stabilize the connector between the alpha and the beta domains; and (3) a beta
      turn, sitting in the middle of a bowl of alpha-helix residues. It is proposed
      that this folding nucleus initiates four helices, A, B, C, and D, three beta
      sheets, and the connector, which corresponds closely to the nucleation of the so
      called fast folding track pathway. As the secondary structures propagate,
      nonconserved residues and functionally conserved residues would form additional
      contacts. The conserved residues are selected with a phylogenetic scheme in which
      single members of subfamilies are selected. Subfamilies are then equally weighted
      to obtain the consensus conservation.

PMID- 11956683
TI  - A phylogenomic study of the OCTase genes in Pseudomonas syringae pathovars: the
      horizontal transfer of the argK-tox cluster and the evolutionary history of
      OCTase genes on their genomes.
AB  - Phytopathogenic Pseudomonas syringae is subdivided into about 50 pathovars due to
      their conspicuous differentiation with regard to pathogenicity. Based on the
      results of a phylogenetic analysis of four genes (gyrB, rpoD, hrpL, and hrpS),
      Sawada et al. (1999) showed that the ancestor of P. syringae had diverged into at
      least three monophyletic groups during its evolution. Physical maps of the
      genomes of representative strains of these three groups were constructed, which
      revealed that each strain had five rrn operons which existed on one circular
      genome. The fact that the structure and size of genomes vary greatly depending on
      the pathovar shows that P. syringae genomes are quite rich in plasticity and that
      they have undergone large-scale genomic rearrangements. Analyses of the codon
      usage and the GC content at the codon third position, in conjunction with
      phylogenomic analyses, showed that the gene cluster involved in phaseolotoxin
      synthesis (argK-tox cluster) expanded its distribution by conducting horizontal
      transfer onto the genomes of two P. syringae pathovars (pv. actinidiae and pv.
      phaseolicola) from bacterial species distantly related to P. syringae and that
      its acquisition was quite recent (i.e., after the ancestor of P. syringae
      diverged into the respective pathovars). Furthermore, the results of a detailed
      analysis of argK [an anabolic ornithine carbamoyltransferase (anabolic OCTase)
      gene], which is present within the argK-tox cluster, revealed the plausible
      process of generation of an unusual composition of the OCTase genes on the
      genomes of these two phaseolotoxin-producing pathovars: a catabolic OCTase gene
      (equivalent to the orthologue of arcB of P. aeruginosa) and an anabolic OCTase
      gene (argF), which must have been formed by gene duplication, have first been
      present on the genome of the ancestor of P. syringae; the catabolic OCTase gene
      has been deleted; the ancestor has diverged into the respective pathovars; the
      foreign-originated argK-tox cluster has horizontally transferred onto the genomes
      of pv. actinidiae and pv. phaseolicola; and hence two copies of only the anabolic
      OCTase genes (argK and argF) came to exist on the genomes of these two pathovars.
      Thus, the horizontal gene transfer and the genomic rearrangement were proven to
      have played an important role in the pathogenic differentiation and
      diversification of P. syringae.

PMID- 11956684
TI  - Positive selection scanning reveals decoupling of enzymatic activities of
      carbamoyl phosphate synthetase in Helicobacter pylori.
AB  - In an effort to detect factors which may be under positive selection, a survey
      for such genes in two pathogenic strains of Helicobacter pylori (J99 and 26695)
      was performed. Based on an analysis of synonymous and nonsynonymous
      substitutions, we identified 19 candidate genes under positive selection. A
      search for homologues with known crystallographic structures revealed Escherichia
      coli carbomoyl phosphate synthetase as a homologue of H. pylori carbamoyl
      phosphate synthetase. Carbamoyl phosphate synthetase as isolated from E. coli is
      a heterodimeric enzyme that possesses two different but coupled functionalities
      and is involved in the first committed step in the separate biosynthetic pathways
      for arginine and pyrimidine nucleotides. In this study, we provide evidence
      indicating that one of these functionalities appears to be under selective
      pressure. Reports from previously published site-directed mutagenesis studies
      point to a decoupling of amidotransferase and synthetase activities. Implications
      of these findings for a metabolic enzyme under positive selection are discussed
      in terms of the mechanisms of H. pylori pathogenesis.

PMID- 11956685
TI  - Sequence variation in the gene encoding the nonstructural 3 protein of hepatitis
      C virus: evidence for immune selection.
AB  - To determine whether the persistent nature of hepatitis C infection is related to
      the emergence of antigenic variants driven by immune selection, we examined the
      sequence heterogeneity in a portion of the hepatitis C virus (HCV) nonstructural
      3 (NS3) gene of a patient infected over the course of more than 2 years. By PCR
      amplification, cloning, and sequencing, we observed several variable and
      conserved regions in the NS3 segment of the HCV genome. All variable regions had
      higher ratios of nonsynonymous/synonymous mutations and encompassed
      immunodominant epitopes, and their locations were not essential to maintain the
      known function of HCV RNA helicase. In contrast, the regions that are critical
      for HCV RNA helicase activity were found to be conserved with lower heterogeneity
      or lower ratios of nonsynonymous/synonymous mutations, and none except one of
      these regions was encoded within immunodominant epitopes. Our results are
      consistent with immune selection of viral variants at the epitope and molecular
      levels that may enable HCV to evade host defenses over time. Plotting the
      relatedness of sequence variants revealed a star topology suggesting that a wild
      type HCV sequence is maintained, unlike HIV.

PMID- 11956686
TI  - Complex and tandem repeat structure of subtelomeric regions in the Taiwan
      cricket, Teleogryllus taiwanemma.
AB  - Telomeres of most insects are composed of simple (TTAGG) (n) repeats that are
      synthesized by telomerase. However, in some dipteran insects such as Drosophila
      melanogaster, (TTAGG) (n) repeats or telomerase activity has not been detected.
      Although telomere structure is well documented in Diptera and Lepidoptera, very
      limited information is available on lower insect groups. To understand general
      aspects of telomere function and evolution in insects, we endeavored to
      characterize structures of the telomeric and subtelomeric regions in a lower
      insect, the Taiwan cricket, Teleogryllus taiwanemma. FISH analysis of this
      insect's chromosomes demonstrated (TTAGG) (n) repeat elements in all distal ends.
      Just proximal to the telomeric repeats, the highly conserved 9-kb long terminal
      unit (LTU) sequences are tandemly repeated. These were observed in four of six
      chromosomes, three autosomal ends, and one X-chromosomal end. LTU sequences
      represent about 0.2% of the T. taiwanemma genome. Each LTU contains a core
      (TTAGG)(8)-like sequence (TRLS) and five types of conserved sequences-ST (short
      telomere associated), J (joint), X, SR (satellite sequence rich), and Y-which
      vary in length from about 150 bp to 2.7 kb. The LTU sequence is defined as ST-J
      TRLS-SR-X-Y-X-Y-X. Most LTU regions may be derived from the ancestral common
      sequence, which is observed in ST regions six times and at many other LTU sites.
      We could not find the LTU-like sequence in three other crickets including the
      closest species, T. emma, suggesting that the LTU in T. taiwanemma has been
      rapidly amplified in subtelomeric regions through recent evolutional events. It
      is also suggested that the highly conserved structure of the LTU is maintained by
      recombination and may contribute to telomere elongation, as seen in dipteran
      insects.

PMID- 11956687
TI  - The cephalopod Loligo bleekeri mitochondrial genome: multiplied noncoding regions
      and transposition of tRNA genes.
AB  - We previously reported the sequence of a 9260-bp fragment of mitochondrial (mt)
      DNA of the cephalopod Loligo bleekeri [J. Sasuga et al. (1999) J. Mol. Evol.
      48:692-702]. To clarify further the characteristics of Loligo mtDNA, we have
      sequenced an 8148-bp fragment to reveal the complete mt genome sequence. Loligo
      mtDNA is 17,211 bp long and possesses a standard set of metazoan mt genes. Its
      gene arrangement is not identical to any other metazoan mt gene arrangement
      reported so far. Three of the 19 noncoding regions longer than 10 bp are 515,
      507, and 509 bp long, and their sequences are nearly identical, suggesting that
      multiplication of these noncoding regions occurred in an ancestral Loligo mt
      genome. Comparison of the gene arrangements of Loligo, Katharina tunicata, and
      Littorina saxatilis mt genomes revealed that 17 tRNA genes of the Loligo mt
      genome are adjacent to noncoding regions. A majority (15 tRNA genes) of their
      counterparts is found in two tRNA gene clusters of the Katharina mt genome.
      Therefore, the Loligo mt genome (17 tRNA genes) may have spread over the genome,
      and this may have been coupled with the multiplication of the noncoding regions.
      Maximum likelihood analysis of mt protein genes supports the clade Mollusca +
      Annelida + Brachiopoda but fails to infer the relationships among Katharina,
      Loligo, and three gastropod species.

PMID- 11956688
TI  - Evidence of gene conversion events between paralogous sequences produced by
      tetraploidization in Salmoninae fish.
AB  - We investigated the occurrence of gene conversions between paralogous sequences
      of Salmoninae derived from ancestral tetraploidization and their effect on the
      evolutionary history of DNA sequences. A microsatellite with long flanking
      regions (750 bp) including both coding and noncoding sequences was analyzed.
      Microsatellite size polymorphism was used to detect the alleles of both
      paralogous counterparts and infer linkage arrangement between loci. DNA
      sequencing of seven Salmoninae species revealed that paralogous sequences were
      highly differentiated within species, especially for noncoding regions. Ten gene
      conversion events between paralogous sequences were inferred. While these events
      appears to have homogenized regions of otherwise highly differential paralogous
      sequences, they amplified the differentiation among orthologous sequences. Their
      effects were larger on coding than on noncoding regions. As a consequence,
      noncoding sequences grouped by orthologous lineages in phylogenetic trees,
      whereas coding regions grouped by taxa. Based upon these results, we present a
      model showing how gene conversion events may also result in the PCR amplification
      of nonorthologous sequences in different taxa, with obvious complications for
      phylogenetic inferences, comparative mapping, and population genetic studies.

PMID- 11956689
TI  - Clustering of tissue-specific genes underlies much of the similarity in rates of
      protein evolution of linked genes.
AB  - Are genes nonrandomly distributed around the genome and might this explain why it
      was found that, in the mouse genome, proteins of linked genes evolve at similar
      rates? Anecdotal evidence suggests that the similarity of expression of linked
      genes might, in part, explain the similarity in their rates of evolution. Immune
      system genes, for example, are known to evolve at a high rate and sometimes
      cluster in the genome. Here we develop methods for statistical tests of
      similarity of expression of linked genes and report that there is a significant
      tendency for genes of similar expression breadth to be linked. Significantly,
      when we exclude tissue specific genes from our sample, the similarity in rates of
      protein evolution of linked genes is greatly diminished, if not abolished. This
      diminution is not a sampling artifact. In contrast, while half of the immune
      genes in our sample reside in 1 of 10 immune clusters in the mouse genome, this
      clustering appears not to affect the extent of local similarity in rates of
      evolution. The distribution of placentally expressed genes, in contrast, does
      have an effect.

PMID- 11956690
TI  - Modeling mitochondrial protein evolution using structural information.
AB  - We present two new models of protein sequence evolution based on structural
      properties of mitochondrial proteins. We compare these models with others
      currently used in phylogenetic analyses, investigating their performance over
      both short and long evolutionary distances. We find that our models that
      incorporate secondary structure information from mitochondrial proteins are
      statistically comparable with existing models when studying 13 mitochondrial
      protein data sets from eutherian mammals. However, our models give a
      significantly improved description of the evolutionary process when used with 12
      mitochondrial proteins from a broader range of organisms including fungi, plants,
      protists, and bacteria. Our models may thus be of use in estimating mitochondrial
      protein phylogenies and for the study of processes of mitochondrial protein
      evolution, in particular for distantly related organisms.

PMID- 11956691
TI  - A novel theory on the origin of the genetic code: a GNC-SNS hypothesis.
AB  - We have previously proposed an SNS hypothesis on the origin of the genetic code
      (Ikehara and Yoshida 1998). The hypothesis predicts that the universal genetic
      code originated from the SNS code composed of 16 codons and 10 amino acids (S and
      N mean G or C and either of four bases, respectively). But, it must have been
      very difficult to create the SNS code at one stroke in the beginning. Therefore,
      we searched for a simpler code than the SNS code, which could still encode water
      soluble globular proteins with appropriate three-dimensional structures at a high
      probability using four conditions for globular protein formation (hydropathy,
      alpha-helix, beta-sheet, and beta-turn formations). Four amino acids (Gly [G],
      Ala [A], Asp [D], and Val [V]) encoded by the GNC code satisfied the four
      structural conditions well, but other codes in rows and columns in the universal
      genetic code table do not, except for the GNG code, a slightly modified form of
      the GNC code. Three three-amino acid systems ([D], Leu and Tyr; [D], Tyr and Met;
      Glu, Pro and Ile) also satisfied the above four conditions. But, some amino acids
      in the three systems are far more complex than those encoded by the GNC code. In
      addition, the amino acids in the three-amino acid systems are scattered in the
      universal genetic code table. Thus, we concluded that the universal genetic code
      originated not from a three-amino acid system but from a four-amino acid system,
      the GNC code encoding [GADV]-proteins, as the most primitive genetic code.

PMID- 11956692
TI  - Using homolog groups to create a whole-genomic tree of free-living organisms: an
      update.
AB  - Genomic trees have been constructed based on the presence and absence of families
      of protein-encoding genes observed in 27 complete genomes, including genomes of
      15 free-living organisms. This method does not rely on the identification of
      suspected orthologs in each genome, nor the specific alignment used to compare
      gene sequences because the protein-encoding gene families are formed by grouping
      any protein with a pairwise similarity score greater than a preset value. Because
      of this all inclusive grouping, this method is resilient to some effects of
      lateral gene transfer because transfers of genes are masked when the recipient
      genome already has a homolog (not necessarily an ortholog) of the incoming gene.
      Of 71 genes suspected to have been laterally transferred to the genome of
      Aeropyrum pernix, only approximately 7 to 15 represent genes where a lateral gene
      transfer appears to have generated homoplasy in our character dataset. The
      genomic tree of the 15 free-living taxa includes six different bacterial orders,
      six different archaeal orders, and two different eukaryotic kingdoms. The results
      are remarkably similar to results obtained by analysis of rRNA. Inclusion of the
      other 12 genomes resulted in a tree only broadly similar to that suggested by
      rRNA with at least some of the differences due to artifacts caused by the small
      genome size of many of these species. Very small genomes, such as those of the
      two Mycoplasma genomes included, fall to the base of the Bacterial domain, a
      result expected due to the substantial gene loss inherent to these lineages.
      Finally, artificial "partial genomes" were generated by randomly selecting ORFs
      from the complete genomes in order to test our ability to recover the tree
      generated by the whole genome sequences when only partial data are available. The
      results indicated that partial genomic data, when sampled randomly, could
      robustly recover the tree generated by the whole genome sequences.

PMID- 11956693
TI  - Diversity, distribution, and ancient taxonomic relationships within the TIR and
      non-TIR NBS-LRR resistance gene subfamilies.
AB  - Phylogenetic relationships among the NBS-LRR (nucleotide binding site-leucine
      rich repeat) resistance gene homologues (RGHs) from 30 genera and nine families
      were evaluated relative to phylogenies for these taxa. More than 800 NBS-LRR RGHs
      were analyzed, primarily from Fabaceae, Brassicaceae, Poaceae, and Solanaceae
      species, but also from representatives of other angiosperm and gymnosperm
      families. Parsimony, maximum likelihood, and distance methods were used to
      classify these RGHs relative to previously observed gene subfamilies as well as
      within more closely related sequence clades. Grouping sequences using a distance
      cutoff of 250 PAM units (point accepted mutations per 100 residues) identified at
      least five ancient sequence clades with representatives from several plant
      families: the previously observed TIR gene subfamily and a minimum of four deep
      splits within the non-TIR gene subfamily. The deep splits in the non-TIR
      subfamily are also reflected in comparisons of amino acid substitution rates in
      various species and in ratios of nonsynonymous-to-synonymous nucleotide
      substitution rates ( K(A)/ K(S) values) in Arabidopsis thaliana. Lower K(A)/ K(S)
      values in the TIR than the non-TIR sequences suggest greater functional
      constraints in the TIR subfamily. At least three of the five identified ancient
      clades appear to predate the angiosperm-gymnosperm radiation. Monocot sequences
      are absent from the TIR subfamily, as observed in previous studies. In both
      subfamilies, clades with sequences separated by approximately 150 PAM units are
      family but not genus specific, providing a rough measure of minimum dates for the
      first diversification event within these clades. Within any one clade, particular
      taxa may be dramatically over- or underrepresented, suggesting preferential
      expansions or losses of certain RGH types within particular taxa and suggesting
      that no one species will provide models for all major sequence types in other
      taxa.

PMID- 11956694
TI  - Perfect is the enemy of the very good.

PMID- 11956695
TI  - The ALARA (as low as reasonably achievable) concept in pediatric CT intelligent
      dose reduction. Multidisciplinary conference organized by the Society of
      Pediatric Radiology. August 18-19, 2001.

PMID- 11956699
TI  - Introduction to session I: Helical CT and cancer risk.

PMID- 11956700
TI  - Estimating cancer risks from pediatric CT: going from the qualitative to the
      quantitative.

PMID- 11956701
TI  - Ionizing radiation and cancer risk: evidence from epidemiology.

PMID- 11956702
TI  - Practical dilemmas in implementing benefit-risk protocols.

PMID- 11956705
TI  - CT dose parameters and their limitations.

PMID- 11956706
TI  - Current adult and pediatric CT doses.

PMID- 11956707
TI  - Dose reduction opportunities for CT scanners.

PMID- 11956708
TI  - CT scanner design and patient radiation exposure.

PMID- 11956709
TI  - Effective doses to adult and pediatric patients.

PMID- 11956710
TI  - Pediatric phantoms.

PMID- 11956711
TI  - Introduction: The role of the pediatric radiologist in dose reduction.

PMID- 11956712
TI  - Lessons from history.

PMID- 11956713
TI  - Strategies of dose reduction.

PMID- 11956714
TI  - Questions and discussion.

PMID- 11956715
TI  - Discussion, consensus, and mandate.

PMID- 11956716
TI  - FDA public health notification: reducing radiation risk from computed tomography
      for pediatric and small adult patients.

PMID- 11956717
TI  - Abdominal compartment syndrome in children: CT findings.
AB  - Abdominal compartment syndrome (ACS) is caused by pathological elevation of intra
      abdominal pressure (IAP) leading to multiple organ dysfunction syndrome. Since
      the condition is highly lethal, early diagnosis is imperative. We evaluated the
      pre-operative abdominal CT scans of three children with proven ACS to identify
      signs of elevated IAP. Findings common to these patients included narrowing of
      the inferior vena cava (IVC), direct renal compression or displacement, bowel
      wall thickening with enhancement and a rounded appearance of the abdomen. The aim
      of recognising the CT findings in such cases is to plan emergency surgical
      decompression. Although these findings are not specific for increased IAP,
      radiologists should be aware of this life-threatening condition and, in the
      proper clinical setting, should communicate the presence and significance of
      these findings to the referring clinician.

PMID- 11956718
TI  - Perforation of a central venous catheter into the pelvis of the kidney: a rare
      complication.
AB  - Most adverse events related to central venous catheter (CVC) use in severely ill
      neonates who require total parenteral nutrition (TPN) are caused by malposition
      of the tip of the catheter, followed by complications such as infection, sepsis,
      thrombosis or, rarely, perforation of the vessel. Malpositioned tip of a CVC into
      the renal vein followed by thrombosis is well known. We report two cases of
      perforation of a CVC into the renal pelvis. To prevent this complication, the
      value of intra- or postoperative use of fluoroscopy with injection of contrast
      medium through the catheter is discussed.

PMID- 11956719
TI  - Non-contrast thin-section helical CT of urinary tract calculi in children.
AB  - BACKGROUND: Non-contrast thin-section helical CT has gained acceptance for the
      diagnosis of urinary tract calculi in adults, but experience with the technique
      in children is limited. PURPOSE: To evaluate the utility of non-contrast thin
      section helical CT for the diagnosis of urinary tract calculi in children.
      MATERIALS AND METHODS: Radiology databases at three pediatric institutions were
      searched to identify all pediatric patients evaluated by "renal stone" protocol
      CT scans (no oral or intravenous contrast, scans covering the entire urinary
      tract obtained in helical mode with narrow collimation (< 5 mm)). CT scans were
      reviewed for the primary finding of urinary tract calculi, for secondary signs of
      acute urinary tract obstruction and for evidence of alternative diagnoses.
      Medical records were reviewed to determine clinical presentation and to confirm
      the eventual diagnosis. RESULTS: One hundred thirty-seven scans of 113 children
      (mean age: 11.2 years) were studied. Thirty-eight of 94 examinations (40%)
      performed on 82 children for acute pain and/or hematuria showed ureteral calculi.
      Alternative diagnoses were suggested by CT on 16 scans (17%). Twenty-eight scans
      were performed on 10 asymptomatic children with known calculus disease confirming
      renal stone burden on 21 scans (75%) and persistent ureteral calculi on 6 scans
      (21%). Upper tract calculi were demonstrated on 10 of 15 scans (67%) performed to
      evaluate for calculi in patients with known non-calculus genitourinary tract
      abnormalities. CONCLUSIONS: Non-contrast thin section helical CT is a useful
      method to diagnose urinary tract calculi in children. Radiation dose in this
      retrospective study may exceed the lowest possible radiation dose for diagnostic
      accuracy. Further research is needed to optimize CT imaging parameters, while
      maintaining diagnostic accuracy and minimizing radiation dose.

PMID- 11956720
TI  - Paediatric post-traumatic cortical defects of the distal radius.
AB  - Paediatric post-traumatic cortical defects, although rare, are predominately seen
      affecting the distal radius following a greenstick or torus fracture. We review
      the literature and present a further two cases supported by CT and MRI. Images
      from an acute greenstick fracture are also presented to help understand the
      pathogenesis. Defects are typically solitary on plain radiographs and are usually
      noticed late, proximal to the site of compression. They are non-expansile in an
      otherwise healthy child. CT and MRI may reveal smaller multiple subperiosteal
      defects. Typical defects require no further management other than reassurance and
      advice that they may occasionally cause discomfort but resolve with time.

PMID- 11956721
TI  - CT and MRI findings of cyclosporine-related encephalopathy and hypertensive
      encephalopathy.
AB  - We present the MRI and CT findings of one child with cyclosporine-related
      encephalopathy, and one child with hypertensive encephalopathy following
      cyclosporine-related encephalopathy. The imaging findings were shown well on T2
      weighted and fluid-attenuated inversion recovery (FLAIR) MR images. Cyclosporine
      related encephalopathy was distributed predominantly in the posterior white
      matter. Hypertensive encephalopathy showed similar changes of CT attenuation, but
      with wider distribution. These two disorders seem to have the same pathogenesis.

PMID- 11956722
TI  - Increased inspiratory pressure for reduction of atelectasis in children
      anesthetized for CT scan.
AB  - BACKGROUND: Atelectasis is more frequent and more severe in children anesthetized
      for CT scan than it is in children sedated for CT scan. OBJECTIVE: To determine
      the effect of increased inspiratory pressure on atelectasis during chest CT in
      anesthetized children. MATERIALS AND METHODS: Atelectasis on chest CT was
      assessed by two observers in three groups of patients. Group A comprised 13
      children (26 lungs) anesthetized at inspiratory pressures up to and including 25
      cm H2O. Group B included 11 children anesthetized at inspiratory pressures > or
      =30 cm H2O. Group C included 8 children under deep sedation. RESULTS: Atelectasis
      was significantly more severe in group A than in groups B and C. There was no
      significant difference between groups B and C. CONCLUSION: An inspiratory
      pressure of 30 cm H2O is recommended for children anesthetized for CT scan of the
      chest.

PMID- 11956723
TI  - The development of a pediatric radiology sedation program.
AB  - BACKGROUND: An increase in the number of patients undergoing sedation for imaging
      procedures has led to many changes in practice over the past 10 years. OBJECTIVE:
      The purpose of this study was to compare and evaluate sedation practice changes
      in a pediatric radiology department during the last 5 years. MATERIALS AND
      METHODS: The radiology computer database and corresponding minutes of the
      Radiology Sedation Committee were reviewed to identify changes in sedation
      policy. Data from three blocks of time were analyzed to determine time to
      sedation, time to discharge, drug frequency, rates of adverse events, sedation
      failure, and paradoxical reaction. RESULTS: Specific practice changes undertaken
      over the 5-year period include: (1) increased speed of administration of IV
      pentobarbital, (2) alternating pentobarbital and fentanyl, (3) presedation with
      midazolam, and (4) administering oral pentobarbital to children under and (5)
      over 12 months of age. Based on data analysis, changes 1 and 4 were incorporated
      into the sedation policy, while changes 2, 3, and 5 were abandoned. Comparison of
      data from the three time segments revealed improvement in the time to sedation,
      sedation failure, adverse event, and paradoxical reaction rates. CONCLUSION:
      There is improvement in all aspects of patient outcomes with sedation, as a
      result of several changes in sedation practice.

PMID- 11956724
TI  - Skeletal and total body volumes of human fetuses: assessment of reference data by
      spiral CT.
AB  - OBJECTIVE: To define reference data for skeletal and total body volumes of normal
      human fetuses. MATERIALS AND METHODS: Spiral CT was used to assess the skeletal
      and total body volumes of 31 normal human stillborn infants with gestational age
      (GA) and body weight (BW) ranging from 14 to 41.5 weeks and 22 to 3,760 g,
      respectively. CT scans (slice thickness 2.7 mm, pitch 0.7) were performed within
      the first 24 h after delivery. Precise bone and soft-tissue windows were defined
      from analysis of the density along the diaphysis of the fetal long bones and from
      the measurement of a phantom that mimics soft tissues. Lengths and volumes were
      obtained from 3D reconstructions. The femur lengths measured from CT images
      (FLct) were compared with those provided by US studies (FLus). RESULTS:
      Significant correlations ( r>0.9) were found between BW, measured volumes of the
      entire skeleton or head, long-bone lengths, biparietal diameter and GA. Strong
      linear correlations ( r>0.98) were observed between FLct and FLus. CONCLUSIONS:
      Skeletal and total body volume values obtained using spiral CT were significantly
      correlated with fetal biometric measurements. These data could complement those
      obtained in obstetric investigations with US.

PMID- 11956725
TI  - Infantile leukemia presenting with cholestasis secondary to massive pancreatic
      infiltration.
AB  - We present a 10-week-old infant who presented with cholestasis. Biliary
      obstruction secondary to massive pancreatic infiltration was demonstrated by
      ultrasound. A diagnosis of acute lymphoid leukemia was confirmed. Enlargement of
      the pancreas is unusual both in this age group and in leukemia. Infantile
      leukemia, although rare and usually not associated with gastrointestinal
      presentations, should be considered as a cause of pancreatic enlargement and
      neonatal cholestasis.

PMID- 11956726
TI  - Mesenteric lymphatic malformation associated with small-bowel volvulus - two
      cases and a review of the literature.
AB  - Cystic mesenteric lymphatic malformations are uncommon abdominal masses, which
      can cause abdominal signs and symptoms for a wide variety of reasons. Symptoms
      owing to volvulus are uncommon and have not been illustrated previously in the
      radiology literature. We present two cases to illustrate volvulus as a
      complication of mesenteric lymphatic malformations and how imaging can aid in the
      diagnosis of this complication. While uncommon, volvulus should be considered in
      any child with sonographic findings of an abdominal lymphatic malformation and
      acute abdominal pain.

PMID- 11956727
TI  - Solitary plasmacytoma of the spine in an adolescent: a case report.
AB  - Solitary plasmacytoma of bone is a rare disease in patients younger than 30
      years, and only a few cases have been reported in children and adolescents. We
      report the findings of a destructive lesion of the spine due to solitary
      plasmacytoma in an adolescent patient.

PMID- 11956728
TI  - Painful os styloideum in a child.
AB  - Os styloideum is an immobile bone protrusion, located on the dorsum of the wrist
      between the trapezoid, capitate, and the second and third metacarpals, which may
      be associated with wrist pain. It usually presents in adults after degenerative
      changes occur. We report a case of a 12-year-old girl who presented with os
      styloideum. She was evaluated with plain radiographs, bone scintigraphy, and
      wrist CT. Plain radiographs were initially interpreted as normal. Bone
      scintigraphy demonstrated focal tracer uptake in the right trapezoid. CT
      demonstrated an os styloideum fused to the right trapezoid associated with
      secondary degenerative changes. Os styloideum is a rare cause of wrist pain in
      children.

PMID- 11956729
TI  - Prenatal diagnosis of hypochondrogenesis using fetal MRI: a case report.
AB  - We describe the successful prenatal diagnosis of hypochondrogenesis by MRI. Fetal
      MR findings were the presence of a conspicuous cartilaginous structure in the
      basioccipital region, ill-defined ossification of the cervical vertebral bodies,
      hypoplastic thorax, retarded ossification of the pubic bones, and broad, short
      long bones. In contrast, fetal US revealed only the presence of short long bones.
      MRI accurately delineated the axial skeleton in this case and is an effective
      clinical tool for diagnosing skeletal dysplasias in utero.

PMID- 11956730
TI  - MRI and CT findings of infected cephalhaematoma complicated by skull vault
      osteomyelitis, transverse venous sinus thrombosis and cerebellar haemorrhage.
AB  - We present the CT and MRI findings of an 8-day-old infant with an infected
      cephalhaematoma complicated by skull osteomyelitis, venous sinus thrombosis and
      left cerebellar haemorrhage.

PMID- 11956731
TI  - Treatment and follow-up of pulmonary alveolar microlithiasis with disodium
      editronate: radiological demonstration.
AB  - A 9-year-old girl with pulmonary alveolar microlithiasis is presented. She was
      asymptomatic except for failure to thrive. Plain chest radiographs on admission
      showed sand-like opacities with calcific densities throughout both lung fields,
      predominantly in the lower zones. A black pleural line was also seen between the
      ribs and lung parenchyma. High-resolution CT (HRCT) revealed diffuse ground-glass
      opacities throughout both lungs, micronodular densities, interlobular septal
      thickening, linear calcifications along the pleura and a few scattered subpleural
      cysts. Disodium editronate, which is known to inhibit the microcrystal growth of
      hydroxyapatite, was started at 10 mg/kg per day orally. After 1 year of therapy,
      considerable regression of the calcific densities was detected on chest
      radiographs and HRCT scans.

PMID- 11956732
TI  - Aortic coarctation diagnosed in a hypertensive child undergoing Doppler
      sonography for suspected renal artery stenosis.
AB  - A 5-year-old girl presented with hypertension, with no perceived blood pressure
      differential between the lower and upper extremities. Doppler ultrasound revealed
      a tardus-parvus pattern with diminished systolic acceleration and peak systolic
      velocities in the abdominal aorta and both main renal arteries. Doppler
      interrogation of the suprasternal aorta showed a normal waveform, suggesting a
      partial obstruction distally. Echocardiography and aortography confirmed severe
      discrete aortic coarctation with transverse arch hypoplasia. Because classic
      findings of aortic coarctation may not be present, especially in the older child,
      the radiologist must be aware that a tardus-parvus Doppler waveform in the
      abdominal aorta and bilateral renal arteries is suggestive of proximal aortic
      stenosis, which may be localized by spectral Doppler of the aortic arch.

PMID- 11956733
TI  - Arterial splenic calcifications in children with AIDS: two case reports.
AB  - Splenic calcifications in AIDS patients are usually round and result from
      infections with opportunistic pathogens such as Pneumocystis carinii,
      Mycobacterium avium-intracellulare and Cytomegalovirus. We describe here a
      remarkable echopattern of the spleen in two pediatric patients, resulting from
      linear, branching calcifications in the splenic parenchymal arteries. We believe
      this echopattern represents the ultrasonographic manifestation of an HIV
      associated vasculopathy.

PMID- 11956734
TI  - A snapshot of a 'UFO'.

PMID- 11956735
TI  - Granulocytic sarcoma (chloroma) presenting as a dumbbell tumor.

PMID- 11956737
TI  - Biosynthesis and biotechnological production of statins by filamentous fungi and
      application of these cholesterol-lowering drugs.
AB  - Hypercholesterolemia is considered an important risk factor in coronary artery
      disease. Thus the possibility of controlling de novo synthesis of endogenous
      cholesterol, which is nearly two-thirds of total body cholesterol, represents an
      effective way of lowering plasma cholesterol levels. Statins, fungal secondary
      metabolites, selectively inhibit hydroxymethyl glutaryl-coenzyme A (HMG-CoA)
      reductase, the first enzyme in cholesterol biosynthesis. The mechanism involved
      in controlling plasma cholesterol levels is the reversible inhibition of HMG-CoA
      reductase by statins, related to the structural similarity of the acid form of
      the statins to HMG-CoA, the natural substrate of the enzymatic reaction.
      Currently there are five statins in clinical use. Lovastatin and pravastatin
      (mevastatin derived) are natural statins of fungal origin, while symvastatin is a
      semi-synthetic lovastatin derivative. Atorvastatin and fluvastatin are fully
      synthetic statins, derived from mevalonate and pyridine, respectively. In
      addition to the principal natural statins, several related compounds, monacolins
      and dihydromonacolins, isolated fungal intermediate metabolites, have also been
      characterized. All natural statins possess a common polyketide portion, a hydroxy
      hexahydro naphthalene ring system, to which different side chains are linked. The
      biosynthetic pathway involved in statin production, starting from acetate units
      linked to each other in head-to-tail fashion to form polyketide chains, has been
      elucidated by both early biogenetic investigations and recent advances in gene
      studies. Natural statins can be obtained from different genera and species of
      filamentous fungi. Lovastatin is mainly produced by Aspergillus terreus strains,
      and mevastatin by Penicillium citrinum. Pravastatin can be obtained by the
      biotransformation of mevastatin by Streptomyces carbophilus and simvastatin by a
      semi-synthetic process, involving the chemical modification of the lovastatin
      side chain. The hypocholesterolemic effect of statins lies in the reduction of
      the very low-density lipoproteins (VLDL) and LDL involved in the translocation of
      cholesterol, and in the increase in the high-density lipoproteins (HDL), with a
      subsequent reduction of the LDL- to HDL-cholesterol ratio, the best predictor of
      atherogenic risk. The use of statins can lead to a reduction in coronary events
      related to hypercholesterolemia, but the relationship between benefit and risk,
      and any possible interaction with other drugs, must be taken into account.

PMID- 11956738
TI  - The natural chlorine cycle--fitting the scattered pieces.
AB  - Chlorine is one of the most abundant elements on the surface of the earth. Until
      recently, it was widely believed that all chlorinated organic compounds were
      xenobiotic, that chlorine does not participate in biological processes and that
      it is present in the environment only as chloride. However, over the years,
      research has revealed that chlorine takes part in a complex biogeochemical cycle,
      that it is one of the major elements of soil organic matter and that the amount
      of naturally formed organic chlorine present in the environment can be counted in
      tons per km(2). Interestingly enough, some of the pieces of the chlorine puzzle
      have actually been known for decades, but the information has been scattered
      among a number of different disciplines with little or no exchange of
      information. The lack of communication appears to be due to the fact that the
      points of departure in the various fields have not corresponded; a number of
      paradoxes are actually revealed when the known pieces of the chlorine puzzle are
      fit together. It appears as if a number of generally agreed statements or tacit
      understandings have guided perceptions, and that these have obstructed the
      understanding of the chlorine-cycle as a whole. The present review enlightens
      four paradoxes that spring up when some persistent tacit understandings are
      viewed in the light of recent work as well as earlier findings in other areas.
      The paradoxes illuminated in this paper are that it is generally agreed that: (1)
      chlorinated organic compounds are xenobiotic even though more than 1,000
      naturally produced chlorinated compounds have been identified; (2) only a few,
      rather specialised, organisms are able to convert chloride to organic chlorine
      even though it appears as if the ability among organisms to transform chloride to
      organic chlorine is more the rule than the exception; (3) all chlorinated organic
      compounds are persistent and toxic even though the vast majority of naturally
      produced organic chlorine is neither persistent nor toxic; (4) chlorine is mainly
      found in its ionic form in the environment even though organic chlorine is as
      abundant or even more abundant than chloride in soil. Furthermore, the contours
      of the terrestrial chlorine cycle are outlined and put in a concrete form by
      constructing a rough chlorine budget over a small forested catchment. Finally,
      possible ecological roles of the turnover of chlorine are discussed.

PMID- 11956739
TI  - Biotechnological applications and potential of wood-degrading mushrooms of the
      genus Pleurotus.
AB  - The genus Pleurotus comprises a group of edible ligninolytic mushrooms with
      medicinal properties and important biotechnological and environmental
      applications. The cultivation of Pleurotus spp is an economically important food
      industry worldwide which has expanded in the past few years. P. ostreatus is the
      third most important cultivated mushroom for food purposes. Nutritionally, it has
      unique flavor and aromatic properties; and it is considered to be rich in
      protein, fiber, carbohydrates, vitamins and minerals. Pleurotus spp are promising
      as medicinal mushrooms, exhibiting hematological, antiviral, antitumor,
      antibiotic, antibacterial, hypocholesterolic and immunomodulation activities. The
      bioactive molecules isolated from the different fungi are polysaccharides. One of
      the most important aspects of Pleurotus spp is related to the use of their
      ligninolytic system for a variety of applications, such as the bioconversion of
      agricultural wastes into valuable products for animal feed and other food
      products and the use of their ligninolytic enzymes for the biodegradation of
      organopollutants, xenobiotics and industrial contaminants. In this Mini-Review,
      we describe the properties of Pleurotus spp in relation to their biotechnological
      applications and potential.

PMID- 11956740
TI  - Diastereoselective synthesis of optically active (2 R,5 R)-hexanediol.
AB  - Diastereoselective reduction of diketones with Lactobacillus kefir DSM 20587 was
      examined. The reduction of both oxo-functions proceeded highly
      diastereoselectively. (2 R,5 R)-Hexanediol 3 was produced starting from (2,5)
      hexanedione 1 in quantitative yields with enantiomeric excess >99% and
      diastereomeric excess >99%. The reaction conditions were optimized: maximum yield
      of (2 R,5 R)-hexanediol was reached at pH 6, 30 degrees C and with equal amounts
      of substrate and cosubstrate. The applicability of the system in fed-batch
      experiments was demonstrated. The feed specific biomass concentration required to
      reach maximal yield and selectivity in fed-batch mode was determined.

PMID- 11956741
TI  - Improvement of mass transfer characteristics and productivities of inclined
      tubular photobioreactors by installation of internal static mixers.
AB  - The feasibility of improving mass transfer characteristics of inclined tubular
      photobioreactors by installation of static mixers was investigated. The mass
      transfer characteristics of the tubular photobioreactor varied depending on the
      type (shape) and the number of static mixers. The volumetric oxygen transfer
      coefficient ( k(L)a) and gas hold up of the photobioreactor with internal static
      mixers were significantly higher than those of the photobioreactor without static
      mixers. The k(L)a and gas hold up increased with the number of static mixers but
      the mixing time became longer due to restricted liquid flow through the static
      mixers. By installing the static mixers, the liquid flow changed from plug flow
      to turbulent mixing so that cells were moved between the surface and bottom of
      the photobioreactor. In outdoor culture of Chlorella sorokiniana, the
      photobioreactor with static mixers gave higher biomass productivities
      irrespective of the standing biomass concentration and solar radiation. The
      effectiveness of the static mixers (average percentage increase in the
      productivities of the photobioreactor with static mixers over the productivities
      obtained without static mixers) was higher at higher standing biomass
      concentrations and on cloudy days (solar radiation below 6 MJ m(-2) day(-1)).

PMID- 11956742
TI  - Degradation of lignocellulose by extracellular enzymes produced by
      Thermomonospora fusca BD25.
AB  - Degradation products from the addition of extracellular enzymes from
      Thermomonospora fusca BD25 to ball-milled wheat straw, oat spelt xylan and
      solubilised kraft pulps were characterised by HPLC and TLC. Overall, a high
      percentage hydrolysis of oat spelt xylan (28.9%) occurred after 26 h incubation.
      However, the rates of hydrolysis of ball-milled wheat straw and kraft pulp were
      approximately 4-6-fold less than xylan hydrolysis, although the total percentage
      hydrolysis of available substrate was similar (22.2% and 25.9% respectively).
      Incubation of kraft pulp and ball-milled wheat straw by crude extracellular
      enzymes of T. fusca BD25 resulted in the detection of aromatic compounds at
      concentrations of 0.6 microg ml(-1) and 8.7 microg ml(-1), respectively.
      Hydrolysis of oat spelt xylan by T. fusca BD25 extracellular enzymes yielded a
      mixture of xylose, xylotriose and putative substituted-xylotriose, while the
      products of ball-milled wheat straw hydrolysis were xylose, glucose and a small
      oligomer present in the digest. The results highlight the ability of culture
      supernatant from T. fusca to release both simple sugars and aromatic compounds
      from lignocellulosic substrates and suggest a role for this organism in the
      biobleaching of pulp.

PMID- 11956743
TI  - A molybdenum-containing dehydrogenase catalyzing an unusual 2-hydroxylation of
      nicotinic acid.
AB  - An enzyme of Ralstonia/ Burkholderia strain DSM 6920 catalyzing the initial
      hydroxylation of 6-methylnicotinic acid at position 2 was purified to apparent
      homogeneity. It also catalyzed the unusual conversion of nicotinic acid to 2
      hydroxynicotinic acid and was therefore designated as nicotinic acid
      dehydrogenase (NDH). Native NDH had a molecular mass of 280 kDa and was composed
      of subunits of 75, 30 and 16 kDa. It contained molybdenum, iron, acid-labile
      sulfur and FAD in a ratio of 1.6:7.3:8.0:0.6 mol(-1) of native enzyme. The
      molybdenum cofactor was characterized as molybdopterin cytosine dinucleotide.
      Zinc was identified as an additional metal ion in a molar ratio of 1.8 mol mol(
      1) of native enzyme. Purified NDH exhibited a maximal specific activity of 22.6
      micromol nitro blue tetrazoliumchloride reduced min(-1) mg(-1) of protein, using
      nicotinic acid as electron donor. The apparent K(m) value for nicotinic acid was
      determined to be 154 microM. Pyridine-3,5-dicarboxylic acid and quinoline-3
      carboxylic acid were further substrates, but exhibited significantly different
      activity pH optima. Several artificial electron acceptors were reduced by NDH,
      but no activity was detected with NAD or O(2). NDH was inactivated upon
      incubation with cyanide, but no loss of activity was obtained in the presence of
      arsenite.

PMID- 11956744
TI  - Disruption of the uptake hydrogenase gene, but not of the bidirectional
      hydrogenase gene, leads to enhanced photobiological hydrogen production by the
      nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120.
AB  - In order to determine the effects of the deletion of hydrogenase genes on
      nitrogenase-based photobiological H(2) productivity by heterocystous N(2)-fixing
      cyanobacteria, we have constructed three hydrogenase mutants from Anabaena sp.
      PCC 7120: hupL(-) (deficient in the uptake hydrogenase), hoxH(-) (deficient in
      the bidirectional hydrogenase), and hupL(-)/ hoxH(-) (deficient in both genes).
      The hupL(-) mutant produced H(2) at a rate four to seven times that of the wild
      type under optimal conditions. The hoxH(-) mutant produced significantly lower
      amounts of H(2) and had slightly lower nitrogenase activity than wild-type. H(2)
      production by the hupL(-)/ hoxH(-) mutant was slightly lower than, but almost
      equal to, that of the hupL(-) mutant. The efficiency of light energy conversion
      to H(2) by the hupL(-) mutant at its highest H(2) production stage was 1.2% at an
      actinic visible light intensity of 10 W/m(2) (PAR) under argon atmosphere. These
      results indicate that deletion of the hupL gene could be employed as a source for
      further improvement of H(2) production in a nitrogenase-based photobiological
      H(2) production system.

PMID- 11956745
TI  - Development of molecular tools for the mulundocandin producer Aspergillus
      sydowii: DNA-mediated transformation and reporter gene expression.
AB  - The echinocandin-type antimycotic mulundocandin and its derivatives are produced
      by the filamentous fungus Aspergillus sydowii (strain FH2551). These agents have
      been considered as a potential drug to treat immunocompromised patients who
      suffer from severe opportunistic fungal infections. In order to generate strains
      with a modified mulundocandin biosynthesis, we developed molecular tools for
      genetic engineering of A. sydowii as an alternative to conventional strain
      improvement procedures. For our experiments, we used strain FH2551, which was
      discriminated from other Aspergillus strains by determining the sequence of the
      two internal transcribed spacers (ITS1 and ITS2) of the rDNA locus. In addition,
      the electrophoretic karyotype of A. sydowii was established using pulsed-field
      gel electrophoresis (PFGE), leading to a calculated genomic size of about 40 Mb.
      For gene mapping, chromosomes were subjected to PFGE either unrestricted or after
      incubation with rare cutting enzymes and probed with heterologous genes. Using
      the bacterial hygromycin B phosphotransferase gene as a selectable marker for
      transformation of A. sydowii, we generated transformants with single and multiple
      copies of plasmid DNA. Subsequently, the heterologous lacZ and gfp genes were
      efficiently transferred and expressed in A. sydowii. The majority of lacZ
      transformants showed more than 6 pkat beta-galactosidase activity/mg protein,
      while the control strains had no significant background activity. Fluorescence
      microscopy of gfp-transformants demonstrated that the green-fluorescent protein
      is present in a stable and active form in the cytoplasm of vegetative hyphae and
      conidiospores.

PMID- 11956746
TI  - Characterization of a partial duplication of the aflatoxin gene cluster in
      Aspergillus parasiticus ATCC 56775.
AB  - A partial duplication of the complete aflatoxin gene cluster containing
      homologues of aflR-aflJ-adhA-estA-norA-ver1and omtB was identified from
      Aspergillus parasiticus ATCC 56775. The genes, verA-avnA-verB-avfA, between ver1
      and omtB in the complete gene cluster, however, were not found. One-hybrid assays
      showed that the duplicated aflRgene ( aflR2) encoded a protein that could
      activate transcription just as that encoded by aflR1,the aflR gene in the
      complete gene cluster. Two-hybrid assays showed that AFLR2 also interacted with a
      putative coactivator, AFLJ1, at comparable levels to AFLR1. Deletion of aflR1
      resulted in the loss of production of aflatoxin precursors, which suggested that
      aflR2could not completely replace the function of aflR1. Point mutations found in
      adhA2, pre-termination in ver1B and norA2,and a large deletion in omtB2 probably
      render these duplicated genes to become nonfunctional. A close examination of the
      history of isolates reported to have a partial duplication suggested that
      duplication of the aflatoxin cluster is not a prevalent event.

PMID- 11956747
TI  - Spacer-elongated cell wall fusion proteins improve cell surface expression in the
      yeast Saccharomyces cerevisiae.
AB  - Fusion proteins for cell surface expression in the yeast Saccharomyces cerevisiae
      were constructed that consisted of the N-terminal leader sequence of Kre1p,
      followed by the nine amino acid viral epitope hemagglutinin (HA), and the
      carboxyterminal anchoring domain of either Cwp2p or Flo1p. All fusions were
      constitutively expressed under transcriptional control of the phosphoglycerate
      kinase promoter and immunofluorescence analysis indicated that in each construct
      the HA peptide was correctly anchored to the outer yeast cell surface. Successful
      solubilization of the cell wall fusions by laminarinase treatment indicated that
      the fusions are covalently linked to cell wall beta-1,3- D-glucans in vivo. FACS
      analyses further demonstrated that 70% of the yeast cell population expressed the
      corresponding cell wall fusion. Neither the number of positive cells within the
      population nor the distribution of the fusion at the single-cell level were
      negatively affected by replacing the "heterologous" Kre1p leader by the "native"
      Cwp2p leader. Insertion of a 350 amino acid Ser/Thr-rich spacer sequence into the
      fusions led to a dramatic increase in HA peptide accessibility on the yeast cell
      surface. Our data show that FACS analyses represent a valuable means for
      investigating cell surface expression, and indicate that artificial-spacer
      elongated cell wall fusions might raise novel possibilities for cell surface
      expression of heterologous proteins in yeast.

PMID- 11956748
TI  - Construction of a flocculent Saccharomyces cerevisiae strain secreting high
      levels of Aspergillus niger beta-galactosidase.
AB  - A flocculent Saccharomyces cerevisiae strain secreting Aspergillus niger beta
      galactosidase activity was constructed by transforming S. cerevisiae NCYC869-A3
      strain with plasmid pVK1.1 harboring the A. niger beta-galactosidase gene, lacA,
      under the control of the ADH1 promoter and terminator. Compared to other
      recombinant S. cerevisiae strains, this recombinant yeast has higher levels of
      extracellular beta-galactosidase activity. In shake-flask cultures, the beta
      galactosidase activity detected in the supernatant was 20 times higher than that
      obtained with previously constructed strains (Domingues et al. 2000a). In
      bioreactor culture, with cheese-whey permeate as substrate, a yield of 878.0
      nkat/gsubstrate was obtained. The recombinant strain is an attractive alternative
      to other fungal beta-galactosidase production systems as the enzyme is produced
      in a rather pure form. Moreover, the use of flocculating yeast cells allows for
      enzyme production with high productivity in continuous fermentation systems with
      facilitated downstream processing.

PMID- 11956749
TI  - Pitting corrosion inhibition of aluminum 2024 by Bacillus biofilms secreting
      polyaspartate or gamma-polyglutamate.
AB  - Pitting corrosion of aluminum 2024 in Luria Bertani medium was reduced by the
      secretion of anionic peptides by engineered and natural Bacillus biofilms and was
      studied in continuous reactors using electrochemical impedance spectroscopy.
      Compared to sterile controls, pitting was reduced dramatically by the presence of
      the biofilms. The secretion of a 20 amino acid polyaspartate peptide by an
      engineered Bacillus subtilis WB600/pBE92-Asp biofilm slightly reduced the
      corrosion rate of the passive aluminum alloy at pH 6.5; however, the secretion of
      gamma-polyglutamate by a Bacillus licheniformis biofilm reduced the corrosion
      rate by 90% (compared to the B. subtilis WB600/pBE92 biofilm which did not
      secrete polyaspartate or gamma-polyglutamate). The corrosion potential ( E(corr))
      of aluminum 2024 was increased by about 0.15-0.44 V due to the formation of B.
      subtilis and B. licheniformis biofilms as compared to sterile controls. The
      increase of E(corr) and the observed prevention of pitting indicate that the
      pitting potential ( E(pit)) had increased. This result and the further decrease
      of corrosion rates for the passive aluminum alloy suggest that the rate of the
      anodic metal dissolution reaction was reduced by an inhibitor produced by the
      biofilms. Purified gamma-polyglutamate also decreased the corrosion rates of
      aluminum 2024.

PMID- 11956750
TI  - Description of a cellulose-binding domain and a linker sequence from Aspergillus
      fungi.
AB  - A family I cellulose-binding domain (CBD) and a serine- and threonine-rich linker
      peptide were cloned from the fungi Aspergillus japonicus and Aspergillus
      aculeatus. A glutathione S-transferase (GST) fusion protein comprising GST and a
      peptide linker with the CBD fused to its C-terminus, was expressed in Escherichia
      coli. The renatured GST-CBD recovered from inclusion bodies had a molecular mass
      of 36.5 kDa which agrees with the 29 kDa of the GST plus the calculated 7.5 kDa
      of the linker with the CBD. The isolated GST-CBD protein adsorbed to both
      bacterial microcrystalline cellulose and carboxymethyl cellulose. Deletion of the
      linker peptide caused a decrease in cellulose adsorbance and a higher sensitivity
      to protease digestion.

PMID- 11956751
TI  - Isolation and characterization of a new succinic acid-producing bacterium,
      Mannheimia succiniciproducensMBEL55E, from bovine rumen.
AB  - A novel succinic acid-producing bacterium was isolated from bovine rumen. The
      bacterium is a non-motile, non-spore-forming, mesophilic and capnophilic gram
      negative rod or coccobacillus. Phylogenetic analysis based on the 16S rRNA
      sequence and physiological analysis indicated that the strain belongs to the
      recently reclassified genus Mannheimia as a novel species, and has been named
      Mannheimia succiniciproducens MBEL55E. Under 100% CO(2) conditions, it grows well
      in the pH range of 6.0-7.5 and produces succinic acid, acetic acid and formic
      acid at a constant ratio of 2:1:1. When M. succiniciproducensMBEL55E was cultured
      anaerobically in medium containing 20 g l(-1) glucose as carbon source, 13.5 g l(
      1) of succinic acid was produced.

PMID- 11956752
TI  - Effects of high and fluctuating pressure on microbial abundance and activity in a
      water hydraulic system.
AB  - The effects of high and fluctuating pressure up to 220 bar on microbial growth
      and activity were determined in a pilot-scale water hydraulic system. An increase
      in the pipeline pressure from 70 to 220 bar decreased the total and the viable
      cell number in the pressure medium from 2.2(+/-0.5)x10(5) to 4.9(+/-1.5)x10(4)
      cells/ml and from 5.7(+/-2.8)x10(4) to 1.3(+/-0.7)x10(4) cfu/ml, respectively.
      Microbial attachment in the non-pressurised tank of the hydraulic system
      increased with increasing pipeline pressure [from 1.0(+/-0.3) to 3.8(+/
      2.7)x10(5) cells/cm(2) on stainless steel]. The phosphatase, aminopeptidase and
      beta-glucosidase activities in the pressurised medium were between 0.02 and 1.4
      micromol/lh ( V(max)) and decreased in response to increasing pipeline pressure.
      The alpha-glucosidase activity was detected only at 70 bar and the glucuronidase
      activity only occasionally. Based on principal component and cluster analyses,
      both the pressure applied and the original filling water quality affected
      substrate utilisation patterns. This study demonstrated the capability of
      freshwater bacteria to tolerate high and fluctuating pressure in a technical
      water system. Microbial survival was due to attachment and growth on the surfaces
      of the non-pressurised components and the nutrient flux released by cell lysis in
      the pressurised components. In summary, high pressures in water hydraulic systems
      do not prevent potential microbiologically related operational problems.

PMID- 11956753
TI  - Autotrophic synthesis of polyhydroxyalkanoates by the bacteria Ralstonia eutropha
      in the presence of carbon monoxide.
AB  - It has been found that the carbon monoxide (CO)-resistant strain of the hydrogen
      bacteria Ralstonia eutropha B5786 is able to synthesise polyhydroxyalkanoates
      (PHAs) in the presence of CO under autotrophic conditions. This strain, grown on
      model gas mixtures containing 5-25% CO (v/v), accumulates up to 70-75% (of
      absolutely dry matter) PHA, without significant variation in the yield
      coefficient on hydrogen. No suppression of the activities of the key enzymes of
      PHA synthesis ( beta-ketothiolase, acetoacetyl-CoA-reductase, butyrate
      dehydrogenase and poly-3-hydroxybutyrate synthase) was recorded. The PHA
      synthesised is a co-polymer containing mostly beta-hydroxybutyrate (more than 99
      mol%) with trace amounts of beta-hydroxyvalerate. The investigated properties of
      the polymer (molecular weight, crystallinity, temperature characteristics) do not
      differ from those of the polymer synthesised on electrolytic hydrogen.

PMID- 11956754
TI  - Degradation of aniline by newly isolated, extremely aniline-tolerant Delftia sp.
      AN3.
AB  - A bacterial strain, AN3, which was able to use aniline or acetanilide as sole
      carbon, nitrogen and energy sources was isolated from activated sludge and
      identified as Delftiasp. AN3. This strain was capable of growing on
      concentrations of aniline up to 53.8 mM (5000 mg/l). Substituted anilines such as
      N-methylaniline, N, N-dimethylaniline, 2-methylaniline, 4-methylaniline, 2
      chloroaniline, 3-chloroaniline, o-aminoaniline, m-aminoaniline, p-aminoaniline,
      and sulfanilic acid did not support the growth of strain AN3. The optimal
      temperature and pH for growth and degradation of aniline were 30 degrees C and
      7.0, respectively. The activities of aniline dioxygenase, catechol 2,3
      dioxygenase and other enzymes involved in aniline degradation were determined,
      and results indicated that all of them were inducible. The K (m) and V (max) of
      aniline dioxygenase were 0.29 mM and 0.043 mmol/mg protein/min, respectively. The
      K (m) and V (max) of catechol 2, 3-dioxygenase for catechol were 0.016 mM and
      0.015 mmol/mg protein/min, respectively. Based on the results obtained, a pathway
      for the degradation of aniline by Delftiasp. AN3 was proposed. The importance of
      the strain to the operation of municipal wastewater treatment plants is
      discussed.

PMID- 11956756
TI  - Biodegradation of volatile organic compounds by five fungal species.
AB  - Five fungal species, Cladosporium resinae (ATCC 34066), Cladosporium
      sphaerospermum (ATCC 200384), Exophiala lecanii-corni (CBS 102400), Mucor rouxii
      (ATCC 44260), and Phanerochaete chrysosporium (ATCC 24725), were tested for their
      ability to degrade nine compounds commonly found in industrial off-gas emissions.
      Fungal cultures inoculated on ceramic support media were provided with volatile
      organic compounds (VOCs) via the vapor phase as their sole carbon and energy
      sources. Compounds tested included aromatic hydrocarbons (benzene, ethylbenzene,
      toluene, and styrene), ketones (methyl ethyl ketone, methyl isobutyl ketone, and
      methyl propyl ketone), and organic acids ( n-butyl acetate, ethyl 3
      ethoxypropionate). Experiments were conducted using three pH values ranging from
      3.5 to 6.5. Fungal ability to degrade each VOC was determined by observing the
      presence or absence of visible growth on the ceramic support medium during a 30
      day test period. Results indicate that E. lecanii-corni and C. sphaerospermum can
      readily utilize each of the nine VOCs as a sole carbon and energy source. P.
      chrysosporium was able to degrade all VOCs tested except for styrene under the
      conditions imposed. C. resinae was able to degrade both organic acids, all of the
      ketones, and some of the aromatic compounds (ethylbenzene and toluene); however,
      it was not able to grow utilizing benzene or styrene under the conditions tested.
      With the VOCs tested, M. rouxiiproduced visible growth only when supplied with n
      butyl acetate or ethyl 3-ethoxypropionate. Maximum growth for most fungi was
      observed at a pH of approximately 5.0. The experimental protocol utilized in
      these studies is a useful tool for assessing the ability of different fungal
      species to degrade gas-phase VOCs under conditions expected in a biofilter
      application.

PMID- 11956757
TI  - Dynamic bioreactor operation: Effects of packing material and mite predation on
      toluene removal from off-gas.
AB  - Recent studies have focused on using vapor-phase bioreactors for the treatment of
      volatile organic compounds from contaminated air streams. Although high removal
      capacities have been achieved in many studies, long-term operation is often
      unstable at high pollutant loadings due to biomass accumulation and drying of the
      packing medium. In this study, three bench-scale bioreactors were operated to
      determine the effect of packing material and fungal predation on toluene removal
      efficiency and pressure drop. Toluene elimination capacities (mass toluene
      removed per unit packing per unit time) above 100 g m(-3) h(-1) were obtained in
      the fungal bioreactors packed with light-weight, artificial medium, and
      submersion of the packing in mineral medium once per week was found to provide
      sufficient moisture and nutrients to the biofilm. The use of mites as fungal
      predators improved performance by increasing the overall mineralization of
      toluene to CO(2), and by dislodging biomass along the bioreactor.

PMID- 11956758
TI  - Genetic dissection of complex and quantitative traits: from fantasy to reality
      via a community effort.

PMID- 11956759
TI  - exma: an X-linked insertional mutation that disrupts forebrain and eye
      development.
AB  - Formation of the neural tube plays a primary role in establishing the body plan
      of the vertebrate embryo. Here we describe the phenotype and physical mapping of
      a highly penetrant X-linked male-lethal murine mutation, exma (exencephaly,
      microphthalmia/anophthalmia), that specifically disrupts development of the
      rostral neural tube and eye. The mutation arose from the random insertion of a
      transgene into the mouse X Chromosome (Chr). Eighty-three percent of transgenic
      male embryos display an open, disorganized forebrain and lack optic vesicles. No
      transgenic males survive beyond birth. Hemizygous females show a variable
      phenotype, including reduced viability and occasional exencephaly and/or
      microphthalmia. Altered or reduced expression patterns of Otx2, Pax6, Six3, and
      Mrx, known markers of early forebrain and eye development, confirmed the highly
      disorganized structure of the forebrain and lack of eye development in affected
      exma male embryos. Physical mapping of the transgene by FISH localized a single
      insertion site to the interval between Dmd and Zfx on the X Chr. A 1-Mb contig of
      BAC clones was assembled by using sequences flanking the transgene and revealed
      that the insertion lies close to Pola1 and Arx, a gene encoding a highly
      conserved homeobox protein known to be expressed in the developing forebrain of
      the mouse. Data from Southern blots of normal and transgenic DNA demonstrated
      that a large segment of DNA encompassing Arx and including part of Pola1 was
      duplicated as a result of the transgene insertion. From the physical mapping
      results, we propose a model of the gross rearrangements that accompanied
      transgene integration and discuss its implications for evaluating candidate genes
      for exma.

PMID- 11956760
TI  - The mouse Fused toes (Ft) mutation is the result of a 1.6-Mb deletion including
      the entire Iroquois B gene cluster.
AB  - As a result of transgenic insertional mutagenesis, heterozygous Fused toes (Ft)
      mice display a syndactyly of forelimbs and a thymic hyperplasia. Homozygous Ft/Ft
      embryos die in midgestation, exhibiting a deformation of craniofacial structures,
      a syndactyly and a polydactyly of fore- and hindlimbs, a disorganization of the
      ventral spinal cord, and defects in left-right axis formation. Here we report on
      our structural analyses of the Ft mutation. We established a physical as well as
      a gene map of the Ft locus, showing that the transgene integration resulted in a
      deletion of 1.6 Mb of genomic sequences on mouse Chromosome 8. Owing to this
      deletion, six genes, including the entire IroquoisB (IrxB) gene cluster, are
      directly affected by the Ft mutation.

PMID- 11956761
TI  - Predictions based on the rat-mouse comparative map provide mapping information on
      over 6000 new rat genes.
AB  - For identification of ECS ("evolutionarily conserved segments") between rat and
      mouse, 893 rat-mouse orthologous gene-pairs were brought together with zoo-FISH
      analysis. In total, 59 autosomal ECS and 4 X-chromosomal ones were detected.
      Combining FISH and zoo-FISH data, the segments were anchored on the rat
      chromosomes, providing an improved comparative map between the two species. Since
      chromosomal evolution is a slow process, it is reasonable to assume that the
      genome organization, including gene order, is essentially conserved within the
      ECS. In this way we assigned tentative subchromosomal map positions to 303 rat
      genes, for which no regional mapping information was available. Furthermore, the
      concept of prediction mapping was extended to unmapped rat homologs of genes,
      which in the mouse are situated inside or in the vicinity of an ECS. For a total
      of 6669 genes, we predicted a single rat chromosomal position, whereas for
      another 448 genes we could predict that they were located in one of two possible
      positions. Thus, our study has increased the number of genes for which there is
      positional mapping information in the rat almost fivefold.

PMID- 11956762
TI  - Radiation hybrid mapping of 70 rat genes from a data set of differentially
      expressed genes.
AB  - The spontaneously hypertensive rat (SHR) is a model of human essential
      hypertension. Increased blood pressure in SHR is associated with other risk
      factors associated with cardiovascular disease, including insulin resistance and
      dyslipidemia. DNA microarray studies identified over 200 differentially expressed
      genes and ESTs between SHR and normotensive control rats. These clones represent
      candidate genes that may underlie previously detected QTLs in SHR. This study
      made use of the publication of two whole-genome maps to identify positional QTL
      candidates. Radiation hybrid (RH) mapping was used to determine the chromosomal
      locations of 70 rat genes and ESTs from this dataset. Most of the locations are
      novel, but in five cases we identified a definitive map location for genes
      previously mapped by somatic cell hybrids and/or linkage analysis. Genes for
      which the mouse genome map location was already determined mapped to syntenic
      segments in the rat genome map, except for two rat genes whose map locations
      confirmed previous findings. Where synteny comparisons could be made only with
      the human, 74% of the genes mapped in this study lay in a conserved syntenic
      segment. Chromosomal localisation of these mouse and human orthologs to syntenic
      segments produces a high level of confidence in the data presented in this study.
      The data provide new map locations for rat genes and will aid efforts to advance
      the rat genome map. The data may also be used to prioritize candidate QTL genes
      in SHR and other rat strains on the basis of their map location.

PMID- 11956764
TI  - Detection of quantitative trait loci for carcass traits in the pig by using AFLP.
AB  - For evaluation of the suitability of Amplified Fragment Length Polymorphism
      (AFLP) for detection of quantitative trait loci in farm animals, a combination of
      AFLP and selective genotyping has been applied as a rapid screening method for
      marker-QTL associations. Focusing on loci affecting eye muscle area, six extreme
      discordant sib pairs were selected from a Duroc x Berlin Miniature Pig F2
      experimental cross and examined by using 48 AFLP primer combinations. Two
      prominent AFLP markers were converted into simple codominant PCR markers ( STS
      Bo1 and STS-Bo3) and assigned to Sscr4 by physical and linkage mapping. Single
      marker analysis indicated association of the STS markers with a putative QTL
      influencing eye muscle area. Interval mapping confirmed the presence of a
      significant QTL for eye muscle area (Pgenomewide < 0.01) on the Sscr4, with STS
      Bo1 being the closer marker. At the same location, significant effects
      (Pgenomewide < 0.01) on carcass length and backfat thickness were also detected.
      Our results demonstrate the capability of the combination of AFLP analysis and
      selective genotyping as a method for detection of genome regions containing QTL
      in livestock.

PMID- 11956765
TI  - Use of bovine EST data and human genomic sequences to map 100 gene-specific
      bovine markers.
AB  - A system to use bovine EST data in conjunction with human genomic sequence to
      improve the bovine linkage map over the entire genome or on specific chromosomes
      was evaluated. Bovine EST sequence was used to provide primer sequences
      corresponding to bovine genes, while human genomic sequence directed primer
      design to flank introns and produce amplicons of appropriate size for efficient
      direct sequencing. The sequence tagged sites (STS) produced in this way from the
      four sires of the MARC reference families were examined for single nucleotide
      polymorphisms (SNPs) that could be used to map the corresponding genes. With this
      approach, along with a primer/extension mass spectrometry SNP genotyping assay,
      100 ESTs were placed on the bovine genetic linkage map. The first 70 were chosen
      at random from bovine EST-human genomic comparisons. An additional 30 ESTs were
      successfully mapped to bovine Chromosome 19 (BTA19), and comparison of the
      resulting BTA19 map to the position of the corresponding human orthologs on the
      HSA17 draft sequences revealed differences in the spacing and order of genes.
      Over 80% of successful amplicons contained SNPs, indicating that this is an
      efficient approach to generating EST-associated genetic markers. We have
      demonstrated the feasibility of constructing a linkage map based on SNPs
      associated with ESTs and the plausibility of utilizing EST, comparative mapping
      information, and human sequence data to target regions of the bovine genome for
      SNP marker development.

PMID- 11956766
TI  - Organization and integration sites in the human genome of endogenous retroviral
      sequences belonging to HERV-E family.
AB  - The present paper reports the characterization of HERV-E endogenous retroviral
      sequences in the human genome by using three complementary approaches. Firstly,
      we identified genomic clones containing HERV-E by BLAST screening of human DNA
      databases by using the entire sequence of a characterized HERV-E clone (M10976)
      as a query. The genomic structure and integration sites of the HERV-E elements
      were characterized. Secondly, new integration sites of HERV-E elements were
      revealed by a retroviral LTR-arbitrary primer-PCR (RELAP-PCR) technique. BLAST
      analysis of the PCR products identified a subgroup that shows low identity (75%)
      to the original clone M10976 and slightly higher identity (80%) to a closely
      related HERV-E (Ac. n. K02166). Finally, we performed FISH mapping, which
      revealed sites of integration of HERV-E not previously identified at the
      cytogenetic level. A preliminary analysis of genes mapping in the same bands as
      HERV-E integration sites was performed: several loci relevant to physiological
      and/or pathological processes were detected. Our findings may provide clues to
      identify HERV-E integration sites adjacent to genes with important biological
      roles.

PMID- 11956767
TI  - Rapid and efficient detection of transgene homozygosity by FISH of mouse
      fibroblasts.

PMID- 11956768
TI  - Oesophageal atresia: a simplified approach to early management.
AB  - Management following the repair of oesophageal atresia (OA) with
      tracheooesophageal fistula (TOF) in the past included the routine use of an
      intercostal chest drain, a gastrostomy, or a transanastomotic tube (TAT) for
      enteral nutrition and a routine contrast swallow (CS) before oral feeds. There
      has been a trend towards simplification of the management, but this is not
      universal. The aim of this study was to evaluate the safety of a simplified
      management regime in infants undergoing primary repair of OA in a retrospective
      case note review of infants undergoing surgery for OA with TOF under the care of
      one consultant over a 12-year period. Intercostal chest drains, TATs, and CSs
      were not routinely used. Early enteral feeding was initiated and oral feeding was
      allowed in babies of adequate birth weight (BW) and gestation. A CS was only
      performed when there were specific anastomotic concerns. Parameters recorded
      included demographic details, time to first enteral feed by tube or mouth, time
      to full oral feeds, and complications. Forty patients were studied; 17 were
      managed without (group 1) and 23 with (group 2) a TAT. Sex distribution,
      gestational age, and BW were comparable in the two groups. In group 1, the time
      to the establishment of full oral feeds was 2-8 days (average 3.9). Four infants
      developed strictures; 2 were managed with dilatation alone and 2 required
      surgery. In group 2, the time to the establishment of full enteral feeds was 2-12
      days (average 5.9). Four patients developed strictures; 2 underwent an anti
      reflux procedure and a 3rd resection of a cartilaginous remnant. There was 1
      death in a patient with intractable cardiac failure. The majority of infants with
      OA and TOF can thus be safely managed without routine chest drainage or CS. A
      sizeable minority do not require a TAT. Early introduction of oral feeds in the
      non-TAT group is not associated with an increased complication rate.

PMID- 11956769
TI  - Denis Browne's thoracotomy revised.
AB  - The three main issues involved in thoracotomy technique for the repair of
      oesophageal atresia (OA) are: (1) prevention of chest wall deformities; (2)
      adequate surgical exposure; and (3) the cosmetic appearance of the skin scar.
      Adequate surgical exposure should be the first priority. The technique described
      is an endeavour to address all the above concerns, a modification of the
      technique described by Denis Browne that eliminates the risk of injury to the
      long thoracic nerve (LTN). A retrospective analysis from case notes of 70
      children (1974-1997) with OA from a single surgeon's practice was performed. Data
      collected included the presence of complications such as wound problems, chest
      wall deformities, and evidence of nerve palsies including winged scapula. A
      uniform technique of a vertical skin incision in the mid-axillary line,
      preservation of the latissimus dorsi, and division of the serratus anterior
      muscle anterior to its nerve was followed in all cases. No wound infection,
      breakdown, or seroma formation was seen in any case. On long-term followup (range
      1-22 years, mean 10.5 years) no chest wall deformities or nerve palsies were
      observed. This modification gives excellent exposure, avoids injury to the LTN,
      does not lead to chest-wall deformity, and gives a pleasing cosmetic result. The
      scar is hardly noticeable with the arm by the side of the body.

PMID- 11956770
TI  - Herniation through the foramen of Morgagni: early diagnosis and treatment.
AB  - The majority of congenital diaphragmatic hernias (CDH) occur through the foramen
      of Bochdalek; herniation through the foramen of Morgagni (MH) is rare. Fifteen
      children (12 males and 3 females) with congenital MH (7 right, 3 left, 5
      bilateral) were treated over a period of 15 years, comprising 11% of a total of
      135 children with different types of CDH. The majority (12, 80%) had repeated
      chest infections. In 1 the hernia was discovered accidentally during evaluation
      of trauma, and another presented in the neonatal period with acute respiratory
      distress (ARD). The diagnosis was made on plain lateral chest radiograph when
      there was anterior herniation of bowel loops, and in these cases the diagnosis
      was confirmed by barium enema. Computed tomography was useful in preoperative
      diagnosis when the hernia contents were solid. All patients were operated upon
      transabdominally except 1, and in all cases there was a hernia sac. Associated
      anomalies were present in 10 (66.7%) patients: 4 (26.7%) had malrotation, 4
      (26.7%) congenital heart disease, and 3 (20%) Down's syndrome. Our study shows a
      relatively high frequency of MH in our patients. MH rarely presents in the
      neonatal period, but when it does, it causes ARD. The majority of patients with
      MH present beyond the neonatal period with repeated attacks of chest infection,
      and although late-presenting MH is relatively benign, it nevertheless causes
      significant morbidity. Thus, clinical awareness and early diagnosis and surgical
      treatment are important factors.

PMID- 11956771
TI  - Isolated and multisystem hepatic trauma in children: the true role of non
      operative management.
AB  - We retrospectively reviewed children with hepatic injuries (HI) admitted to our
      institutions from January 1982 to December 1999. Specific comparison was made of
      isolated (IHT) and multisystem hepatic trauma (MHT). Over the 18-year period 127
      patients were identified with HI, 91 (71%) with MHT and 36 with IHT. The median
      age was 8 years (range 13 months to 14 years). Motor vehicle injury was the most
      common mechanism in both groups, but bicycle injuries were more common in IHT (
      P<0.001). Shock ( P=0.02), the requirement for blood transfusion ( P<0.001), and
      operative intervention for the HI ( P=0.001) were all significantly more common
      in MHT. The distribution of liver injury grades was similar between the two
      groups. Twenty-two (17.3%) children died and in 18 the HI was the main cause or
      contributed significantly. There were 19 and 3 deaths in the MHT and IHT groups,
      respectively, a difference that was not significant. After excluding children
      with minor HI, 27 (39%) required operative intervention within 24 h of their
      injury. This suggests that the high success rate for non-operative management of
      HIs in the literature may have been biased by the inclusion of a significant
      proportion of subclinical injuries.

PMID- 11956772
TI  - Trypsin activity in stool and duodenal aspirate of neonates for differential
      diagnosis of intestinal obstruction.
AB  - The diagnosis of a non-surgical cause of delayed passage of meconium in a neonate
      may be challenging to the pediatric surgeon. The usefulness of determining
      trypsin activity (TA) in stool and duodenal aspirate for the diagnosis of cystic
      fibrosis (CF) and the existence of an entity called transient deficiency of
      trypsin (TTD) was assessed in 49 neonates over a 14-month period. TA was
      determined by a gelatin liquefaction technique. An absence of TA was considered
      if gelatin liquefaction was seen at a dilution of less than 1:100. Neonates with
      negative activity in both samples were started on supplementary pancreatic
      enzymes (pancreatin) for 1 month. TA was retested in the stool after stopping
      pancreatin for 1 week. Neonates with a return of TA were considered to have TTD;
      those who showed persistent TA deficiency at re-evaluation were investigated for
      CF by sweat iontophoresis. Twenty-one neonates had negative TA (in 1 only stool
      was tested); 13 could be re-evaluated (4 died, 4 were lost to follow-up). Nine
      were found to have TTD as a stool or duodenal sample showed the presence of TA; 3
      of 4 patients with persistent negative TA were confirmed to have CF. One patient
      with normal sweat chloride is awaiting genetic studies. Determination of TA by
      gelatin liquefaction is a simple, rapid, inexpensive, and reliable (sensitivity
      100%, negative predictive value 100%) means to differentiate non-surgical causes
      of intestinal obstruction such as neonatal and postoperative TTD and CF.

PMID- 11956773
TI  - Suppression of elevated plasma interleukin-8 levels due to total ischemia and
      reperfusion of the small intestine by luminal perfusion with fetal bovine serum.
AB  - A previous study demonstrated that continuous enteric luminal perfusion of fetal
      bovine serum (FBS) protects the small intestine from total ischemia/reperfusion
      injury (IRI) and increases the intestinal mass. In this study, we further
      investigated the changes in plasma interleukin-8 (IL-8) level caused by total
      ischemia/reperfusion of the small intestine and the effect of FBS on plasma IL-8
      levels. A 3-h total ischemia was induced in a 15-cm segment of terminal ileum and
      then reperfusion was instituted. Luminal perfusion of FBS was conducted via an
      osmotic minipump connected to the stomach through a fine polyethylene tube,
      starting 3 days prior to total ischemia. The rats were killed after 10 and 30 min
      and 1 and 3 h of total ischemia, and 1, 6, and 12 h or 1, 2, and 3 days after
      initiation of reperfusion. Plasma IL-8 was measured by enzyme-linked
      immunosorbent assay. The results were compared among the FBS-treated and
      untreated groups. The plasma IL-8 level was elevated from 1 h of total ischemia
      to 6 h after initiation of reperfusion ( P< 0.05) with a peak of 641.5 +/- 36.9
      pg/ml in the untreated group and 471.6 +/- 42.2 pg/ml in the treated group.
      Luminal perfusion of FBS significantly suppressed plasma IL-8 levels after 1 h of
      total ischemia and 1 h after initiation of reperfusion ( P< 0.05). The results
      suggest that FBS might play a role in the treatment of total IRI of the small
      intestine.

PMID- 11956774
TI  - Chronic constipation due to Hirschsprung's disease and desmosis coli in a family.
AB  - Five members of a family are described, all of whom suffered from chronic
      constipation and megacolon. Detailed clinical and histologic evaluation of each
      member revealed that two individuals have histologic evidence of desmosis coli
      and three have Hirschsprung's disease, one of whom also has desmosis coli. The
      latter combination has never been described before, either in a family or in a
      single patient. Genetic studies of the family did not reveal an increase in the
      number of shared markers for the RET proto-oncogene, suggesting that this
      previously undescribed familial association is likely not caused by a mutation in
      the RET gene, but by other genetic abnormalities.

PMID- 11956775
TI  - Transanastomotic stents for dismembered pyeloplasty in children.
AB  - Among pediatric urologists, there is a debate whether to drain the upper system
      after pyeloplasty in children. In a prospective, randomized clinical study we
      compared the early and late results of patients operated upon for ureteropelvic
      junction obstruction (UPJO) with or without a transanastomotic stent. Anderson
      Hynes pyeloplasty was performed in 31 children during a 5-year period. In 15 a
      transanastomotic stent with multiple holes was used; the upper system was not
      drained in 16. A Penrose drain was placed in the perinephritic area in all
      patients. Patients were evaluated in regard to the time of removal of the stent
      and the Penrose drain, duration of urine leakage, and duration of hospital stay
      in the early postoperative period, and favorable or unfavorable outcome during
      follow-up. The statistical analysis showed no significant difference in regard to
      the removal time of the stent and Penrose drain, duration of drainage, duration
      of hospitalization, and early or late complications between the groups. Although
      stenting does not increase morbidity, we believe that pyeloplasty can be
      performed in children without upper-tract drainage. A feeding tube with multiple
      holes at the tip is recommended.

PMID- 11956776
TI  - Renal dysplasia in children with posterior urethral valves: a primary or
      secondary malformation?
AB  - Routine prenatal ultrasound examination of the urogenital tract is of importance
      in patients with posterior urethral valves (PUV), because the renal function and
      long-term prognosis of these patients depend on early diagnosis and subsequent
      therapy. Opinion is divided as to whether the often-observed association of PUV
      with renal dysplasia represents a primary malformation or a secondary pathology
      caused by recurrent infections. These aspects should have an influence on
      therapeutic consequences and optimal timing of therapy in order to preserve long
      term renal function. The histology of kidney specimens from 13 children with PUV
      who underwent nephrectomy was reviewed to attempt to differentiate between
      primary dysplastic malformations and secondary pathologies. Clinical data were
      analyzed and compared with the histologic findings. The average age at
      nephrectomy was 29 months (range 3-158 months). Approximately 80% of the
      specimens showed primary dysplastic malformations (mesenchymal or fetal cartilage
      tissue or dysplastic glomeruli and tubuli) in the presence of well-developed
      renal parenchyma. All specimens showed secondary pathologies such as renal
      cortical atrophy, interstitial fibrosis, and interstitial-nephritis atrophy. The
      histologic evidence of well-differentiated renal parenchyma in concurrence with
      dysplastic parenchyma makes infravesical obstruction as the only cause of renal
      alterations in patients with PUV questionable. This coincides with the fact that
      organogenesis of the kidney is terminated at the 12th gestational week and
      secondary renal damage is irreversible at the 20th gestational week, but prenatal
      urinary diversion of the upper urinary tract is feasible in the 20th gestational
      week at the earliest. These facts must be taken into account when considering
      intrauterine urinary diversion.

PMID- 11956763
TI  - Normalized cDNA libraries from a porcine model of orthopedic implant-associated
      infection.
AB  - Staphylococcal infections that result from an alteration in a patient's immune
      response at the surgical site are a major problem in procedures that incorporate
      biomaterials in trauma surgery and joint replacement. Diagnosis of infection
      based on pathogen detection is difficult and exacerbated by increasing numbers of
      partially or totally resistant strains of nosocomial pathogens, particularly
      Staphylococcus aureus. Expression profiling of a host's cellular immune response
      could facilitate the identification of the pathways involved in pathogen
      recognition and eradication and could lead to more rational design of drugs and
      therapies. To this end, we constructed and characterized ten individually tagged
      and directionally cloned cDNA libraries from peripheral blood cells (PBC), spleen
      (Sp), thymus (Th), lymph node (LN), and bone marrow (BM) from immunologically
      naive and challenged pigs as part of an implant-associated orthopedic model of
      deep infection. Three of these libraries were normalized at C(0)(t) values 5, 10,
      20, and 30. The libraries comprise more than 20 million primary transformants
      with an average insert length >1.4 kb. Cluster analysis of 7620 ESTs revealed
      1029 clusters containing an average of 3.6 sequences and 3846 singletons. Gene
      discovery is estimated to be approximately 64%. Searches of public databases
      resulted in 49.3% annotated porcine sequences, of which 22.2% had significant
      homologies to ESTs from a variety of species, and 28.5% were without a
      significant match in any public database. We also identified 9.1% ESTs as
      involved in host cell and organism defense and 11.5% related to cell signaling
      and communication. These sequences, together with the 28.5% appearing as novel,
      are of specific interest to the infectious disease process.

PMID- 11956777
TI  - Cystic atypical mesoblastic nephroma.
AB  - Cystic variants of atypical mesoblastic nephromas are very rare. The present
      communication deals with two such cases encountered in 3- and 6-month-old
      patients. The literature is briefly reviewed. The need for proper diagnosis of
      this tumor to distinguish it from cystic nephroma and Wilms' tumor is
      highlighted.

PMID- 11956778
TI  - The role of DMSA scans in evaluation of the correlation between urinary tract
      infection, vesicoureteric reflux, and renal scarring.
AB  - The correlation between urinary tract infection (UTI), vesicoureteric reflux
      (VUR) and renal scarring was studied in 89 patients (177 renal units; 1 solitary
      kidney) during the period 1997-2000. There were 63 males and 26 females; ages
      ranged from neonates to 14 years. UTI was diagnosed on the basis of a positive
      urine culture, VUR was diagnosed and graded by micturating cystourethrogram
      (MCU), and renal scarring was assessed by technetium 99 m Tc-dimercaptosuccinic
      acid (DMSA) scan. Ultrasonography (US) was done to evaluate renal tract
      dilatation and other structural abnormalities. A follow up DMSA scan was
      performed approximately 6 months after the initial scan. VUR was present in 106
      of the 171 renal units in which it was studied and absent in 65 units. The
      majority of the VUR was grade V. Renal scars were seen in 90 of 177 renal units
      at presentation and in 72 of the 163 renal units studied at follow-up. Some
      information was lacking in 31 patients; hence, the correlation between UTI, VUR,
      and renal scarring was done in 58 patients. The majority of the suspected scars
      at presentation were not seen at follow-up, but most of the established scars
      persisted. Only 2 renal units showed scars for the first time on follow-up. On
      US, approximately 50% of normal kidneys showed either suspicious or established
      scars on DMSA scan, and patients with bilateral abnormality on US showed renal
      scars. Renal scars were seen in 15 of 23 children without VUR, 17 of 18 with
      unilateral VUR, and 16 of 17 with bilateral VUR. Thus, there is a cause-and
      effect relationship between UTI and renal scarring that is made worse by VUR.
      DMSA scans have been shown to be the most reliable method of assessing renal
      scarring, and an abnormal US scan showing upper-tract dilatation or a structural
      abnormality may have a predictive value in the detection of renal scarring.

PMID- 11956779
TI  - Color Doppler ultrasonography in the assessment of vesicoureteric reflux in
      children with bladder dysfunction.
AB  - To determine whether color Doppler ultrasound (DUS) evaluation of ureteric jets
      could predict vesicoureteric reflux (VUR) in children with non-neuropathic and
      neuropathic bladder/sphincter dysfunction, 129 children were evaluated to
      identify the vesicoureteric orifice and measure the distance from the orifice to
      the midline of the dorsal bladder wall (MVU distance). The type of bladder
      dysfunction was determined by urodynamic studies. Forty-two children with no
      history of kidney or bladder disease were examined by DUS as a control group. MVU
      distances were compared between several groups of children with different
      urodynamic findings, and the significance was tested. Jets were visualized in 81%
      of children. MVU distances were significantly lower in children without VUR
      compared to those with VUR. No statistically significant differences were
      observed between children without VUR and those with VUR and more severe
      urodynamic disturbances like dysfunctional voiding. In children with neuropathic
      bladders, jets were visible in only 57% of refluxive units and the range of MVU
      distances was very wide (5-22 mm). If a cut-off point of 10 mm is used, in
      children without bladder dysfunction the sensitivity of MVU measurement in the
      diagnosis of VUR was 87.5% and the specificity 97%. However, in children with non
      neuropathic and neuropathic bladder dysfunction, the sensitivity was only 55% and
      the specificity 79%. Color Doppler (DUS) and measurement of the MVU distance
      proved useful in predicting VUR only in children with normal bladder function. In
      children with neuropathic and non-neuropathic bladder dysfunction it can be used
      to visualize ureteric jets, but cannot replace radiographic or radionuclide
      voiding cystourethrography.

PMID- 11956780
TI  - Semen analysis in post-pubertal patients with posterior urethral valves: a pilot
      study.
AB  - The issues of sexual function and fertility are becoming relevant in patients
      with posterior urethral valves (PUV), as more of them reach adulthood. To
      evaluate the semen of post-pubertal patients with PUV as a determinant of future
      fertility, all such patients (age >16 years) attending the follow-up urology
      clinic of our department from 1985 to December 1999 were contacted. Of the nine
      patients contacted, eight agreed to form the study group. All eight patients were
      asked to provide a post-masturbation semen sample and urine. Semen was analysed
      for pH, viscosity, liquefaction time, sperm morphology, sperm count, motility,
      and agglutination. The patients ages ranged from 16 to 21 years (mean 17.5
      years). One patient with chronic renal failure awaiting a renal transplant
      refused to give a semen sample; two tried but failed to ejaculate on three
      consecutive visits. Their urine was negative for sperm. Of the five patients who
      gave semen, the liquefaction time was high in two. pH ranged from 7.2 to 8, sperm
      counts were 24-80 million. None of the patients had oligospermia. Abnormal sperm
      agglutination was present in four cases; a higher percentage of immotile sperm
      was also present in four. Semen abnormalities in the form of increased
      liquefaction time, abnormal sperm agglutination, and a high percentage of
      immotile sperm were thus seen in the present study. The bearing of these findings
      on subsequent sexual function and fertility remains a matter of speculation.

PMID- 11956781
TI  - Factors affecting outcome of one-stage anterior hypospadias repair: analysis of
      422 cases.
AB  - The repair of hypospadias is among the most difficult problems in urology, as it
      demands the construction of a well-functioning urethra and a good cosmetic
      appearance. We performed a retrospective analysis of 422 cases subjected to one
      stage anterior hypospadias repair between 1982 and 1999 in our clinic and
      investigated the effects of factors like degree of hypospadias, surgical
      technique, and the surgeon's experience on outcome. The operations used were
      MAGPI (91), urethral advancement (10), Mathieu (260), modified Allen-Spence (50),
      onlay island flap (5), and double-faced island flap (6) procedures. The early
      complication rate was 18%, while the final success rate following secondary
      interventions was 95%. The complications included fistula formation in 49 cases
      (12%), flap necrosis in 12 (3%), meatal problems in 12 (3%), residual chordee in
      4 (1%), and urethral stricture in 1 (<1%). Complication rates were significantly
      higher if the meatus was proximal or there was severe chordee and in the first 6
      years of the study. The flap procedures were associated with a higher
      complication rate. It is concluded that one-stage procedures are successful in
      the repair of anterior hypospadias in experienced hands with proper patient
      selection.

PMID- 11956783
TI  - Needlescopic inguinal hernia repair in children.
AB  - The object of the present study was to assess the value and outcome of
      needlescopy in the treatment of inguinal hernia (IH) in 150 children operated
      upon in Al-Mishary Hospital, Riyadh, between October 1997 and October 1999. Their
      ages ranged between 6 and 96 months, (mean 61.6 +/- 28.32 months). There were 130
      males and 20 females; 81 (54%) presented with a right-sided IH and among these
      patients a hidden contralateral hernia was diagnosed in 12 cases (8%). A left
      sided IH was present in 30 (20%) bilateral IHs in 19 cases (12.66%), a recurrent
      hernia in 15 (10%), and an incarcerated hernia in 5 (3.33%). All patients were
      subjected to needlescopic herniotomy using a 2.7-mm telescope and two 2-mm needle
      holders to close the internal ring with a 4/0 PDS suture. The mean duration of
      surgery was 20.6 +/- 4.65 min for unilateral and 26.4 +/- 1.6 min for bilateral
      hernia repair. The mean hospital stay was 18 +/- 3.23 h. The study showed that
      laparoscopic closure of the internal ring in children is feasible, easy, and
      preferable to open surgery. The fact that laparoscopy can diagnose a hidden
      contralateral hernia is an additional advantage.

PMID- 11956782
TI  - Inguinal hernia in preterm infants (< or = 32-week gestation).
AB  - The current incidence of inguinal hernia (IH) in premature infants is not well
      established. It is also unclear whether common co-morbidities in this population,
      i.e., chronic lung disease (CLD) or nutritional status or both contribute to the
      development of IH. The purpose of this study was to establish the epidemiologic
      profile of preterm infants of 32 weeks gestational age (GA) or less at birth with
      IH and determine whether the severity of CLD or poor nutritional status
      predisposes to the development of IH. Perioperative profiles of infants
      undergoing surgery were also reviewed. A retrospective study of 1,057 infants
      born at 23-32 weeks GA from January 1990 to December 1995 was done. Specific risk
      and demographic factors were identified. Factors used to determine severity of
      CLD were: days on intermittent mandatory ventilation (IMV); days on positive
      pressure (IMV + continuous positive airway pressure); and total number of days on
      supplemental oxygen. Overall nutritional status was determined by weight gain in
      g/kg per day. The incidence of IH in preterm infants of 32 weeks GA or less who
      were admitted for 28 days or more was 9.34% (65/696) prior to discharge. The
      incidence in infants weighing 1,500 g or less was 11.11% (63/567) and in infants
      1,000 g or less 17.39% (48/276). All parameters that determined the severity of
      CLD were statistically significant in infants with IH by univariate analysis. In
      a multivariate regression model, male gender was the most important variable that
      was significantly associated with IH (odds ratio OR=9.6; 95% confidence interval
      CI=3.90-23.59), followed by total days on supplemental oxygen (adjusted OR=1.00;
      95% CI= 1.01-1.02). Weight gain (g/kg per day) was not significantly different
      between the two groups. Surgical correction before discharge was well tolerated.
      We conclude that the incidence of IH is GA-dependent. Factors related to severity
      of CLD play a more important role than weight gain in predisposing to IH.

PMID- 11956784
TI  - Quadriceps paresis in pediatric groin surgery.
AB  - A total of 2,624 groin operations were performed in 2,202 infants and children
      aged 6 months-14 years during the last 4.5 years. Preventive analgesia was used
      in all operations, and included ilioinguinal and iliohypogastric nerve block
      combined with inguinal canal infiltration. In 6 patients transient postoperative
      quadriceps muscle paresis (QMP) was noted. They required bed rest and monitoring
      for a few hours, and complete spontaneous recovery was noted in all cases. The
      aim of this study was to examine the incidence of transient QMP following
      regional nerve block and to discuss models of possible prevention.

PMID- 11956785
TI  - Excision with primary closure and suction drainage for pilonidal sinus in
      adolescent patients.
AB  - Controversy persists regarding the treatment of pilonidal sinus (PS). To evaluate
      the efficacy of excision with primary closure and closed-suction drainage in
      adolescent patients, between 1990 and 1999, 34 consecutive patients aged 13-18
      years (mean 16.4) underwent PS excision with primary closure and suction
      drainage. Anesthesia was general in 16 (47%) and spinal in 18 (53%) with a
      statistical age difference ( P< 0.001) (15.5 vs 17.2 years, respectively). No
      complications due to the anesthetic were observed. Twenty-one patients (61.8%)
      had day-case surgery while the others were hospitalized for 2 to 4 days (average
      2.3 days). The drain was removed on postoperative day 2 to 6 (average 2.2).
      Primary healing with no postoperative complications occurred in 30 patients
      (88.2%); 1 underwent partial opening of the wound because of rupture of the
      drainage tube during its removal. Postoperative infections requiring incision,
      drainage, and lay-open occurred in 3 cases (9.1%). No recurrence was found at 12
      month follow-up. One recurrence (2.9%) was noted 3 years after surgery. Excision
      with primary closure and closed-suction drainage as an ambulatory procedure is
      thus a simple and effective method of treatment of uncomplicated PS in
      adolescents.

PMID- 11956786
TI  - Costal cartilage grafting for repair of a recurrent tracheoesophageal fistula in
      a 1.6-kg baby with esophageal atresia.
AB  - A large intraoperative tracheal tear occurred during correction of a type III
      esophageal atresia in a 1,630-g premature baby. It was repaired by primary
      suture. Recurrence of the tracheoesophageal fistula (TEF) was treated operatively
      with esophageal exclusion and costal cartilage grafting (CCG) onto the tracheal
      defect. At 3 months of age, successful esophageal reconstruction was performed
      using a posterior mediastinal colonic interposition. On 27-month follow-up, the
      child was symptom-free and thriving. Surgical options for TEF recurrence and
      intraoperative management of the tracheal air leak are discussed. CCG is
      advocated as an attractive material for tracheal repair even in low-weight
      prematures.

PMID- 11956787
TI  - An unusual cause of stridor: retropharyngeal cold abscess.
AB  - A 15-month-old female presented with a large swelling on the left lateral aspect
      of the neck and respiratory distress, and stridor due to incomplete obstruction
      of the upper airway. A lateral X-ray film and computerized tomography scan of the
      cervical spine showed a retropharyngeal abscess without vertebral involvement.
      Aspiration and contrast revealed it to be a bilobed tubercular abscess. Planned
      external drainage was done after 10 days under anti-tubercular drugs.

PMID- 11956788
TI  - Congenital pulmonary arteriovenous malformations.
AB  - We report the rare case of an 11-year-old boy who presented with intractable
      hypoxaemia and a pulmonary mass. Investigations revealed this to be a pulmonary
      arteriovenous malformation. It was entirely confined to the right middle lobe and
      was successfully treated via a right middle lobectomy. The relevant literature
      with respect to both diagnosis and treatment is reviewed.

PMID- 11956789
TI  - Protrusion of a peritoneal catheter through the umblicus: an unusual complication
      of a ventriculoperitoneal shunt.
AB  - Protrusion of a ventriculoperitoneal (VP) shunt through the umblicus is one of
      the rare complications of shunt insertion reported in the medical literature. One
      such case is presented here in a child in whom a VP shunt had been placed for
      congenital hydrocephalus.

PMID- 11956790
TI  - Rupture of the right hemidiaphragm due to blunt trauma in children: a diagnostic
      dilemma.
AB  - The diagnosis of right-sided diaphragmatic rupture (RDR) due to blunt abdominal
      trauma is often missed in the acute setting, especially in the absence of other
      thoracoabdominal injuries. We describe two such children. The problems associated
      with the diagnosis and management of RDR are discussed to emphasize the need to
      have a high index of suspicion for this entity.

PMID- 11956791
TI  - Multiple gastrointestinal atresias in two consecutive siblings.
AB  - Two consecutive female siblings with multiple gastrointestinal atresias are
      described. The history of consanguinity in the parents and the presence of
      extensive typical pathological lesions suggest a genetically-induced
      developmental fault in the alimentary tract during the early embryonic period.

PMID- 11956792
TI  - Gastroduodenal intussusception due to Peutz-Jeghers syndrome in infancy.
AB  - A case of Peutz-Jeghers Syndrome (PJS) presenting in infancy with gastric-outlet
      obstruction is described. PJS may become symptomatic at any age and should be
      suspected when there are obstructive symptoms or gastrointestinal blood loss in a
      baby with a positive family history. Contrast studies and endoscopy are useful in
      diagnosis and surveillance. Treatment requires a combination of endoscopy and
      laparotomy/laparoscopy. Because of the reported cancer risk, we recommend
      surveillance from the age of diagnosis.

PMID- 11956793
TI  - Spontaneous gastroduodenal disruption in neonate.
AB  - A 2-day-old female presented with massive abdominal distention and respiratory
      distress. An erect abdominal X-ray film revealed a pneumoperitoneum of saddlebag
      configuration. The patient was resuscitated and a peritoneal drain was put
      through the right flank. Air and bile drained, and the respiratory distress was
      relieved. After the patient had stabilised haemodynamically, an exploratory
      laparotomy revealed a total gastroduodenal disruption. A gastrojejunostomy was
      done; the pyloric and duodenal ends were closed in two layers. The postoperative
      course was uneventful. We report this case for its unusual and rare presentation.

PMID- 11956794
TI  - Secondary omental torsion in children: report of two cases and review of the
      literature.
AB  - Torsion of the greater omentum (TGO) may be due to a congenital abnormal
      attachment of its free edge. There are no specific symptoms that allow a
      preoperative differential diagnosis of this condition from common pathologies
      such as acute appendicitis. Attachment of the omentum to the large bowel and the
      absence of concomitant diseases make it possible to distinguish TGO secondary to
      a congenital attachment anomaly from omental infarction, primary TGO, and TGO
      secondary to an acquired attachment anomaly (attachment to cysts, tumours,
      hernias, surgical scars, or perforated bowel segments). Resection of the
      ischaemic portion of the omentum permits complete resolution of the clinical
      symptoms. The authors report two cases of TGO in children due to abnormal
      attachment of the greater omentum to the ascending and transverse colon,
      respectively.

PMID- 11956795
TI  - Preoperative chemoembolization for unresectable hepatoblastoma.
AB  - Complete surgical resection offers the only chance for cure in patients with
      hepatoblastoma (HB). Patients with unresectable lesions are given preoperative
      chemotherapy in an attempt to create a resectable lesion. We present a case of an
      11-month-old with an unresectable stage III HB unresponsive to systemic
      chemotherapy. Transfemoral hepatic-artery chemoembolization resulted in a
      surgically resectable tumor. The patient underwent a right trisegmentectomy with
      complete resection of the tumor and remains tumor-free 24 months postoperatively.
      Salvage chemoembolization can be an effective preoperative modality to convert an
      unresectable tumor into a resectable one.

PMID- 11956796
TI  - An enteric duplication cyst of the pancreas causing abdominal pain and
      pancreatitis in a child.
AB  - A rare case of a gastric duplication in the tail of the pancreas in a child
      presenting with recurrent abdominal pain and evidence of pancreatic calcification
      suggesting pancreatitis was cured by excision of the cyst and adjacent pancreas.
      Congenital causes of pancreatitis are rare, but are curable with surgery. These
      lesions are often misdiagnosed, and patients may be subjected to inappropriate
      surgery. Imaging is sensitive in the detection of such lesions, but the lack of
      specific features necessitates an index of suspicion. Similar cases have been
      described previously, but the pancreatic tail is rarely involved.

PMID- 11956797
TI  - Congenital H-type rectourethral fistula.
AB  - An H-type rectourethal fistula was seen in a male child. The anus and anterior
      urethra were normal. The embryology and surgical management of this rare anomaly
      are discussed.

PMID- 11956798
TI  - Anal-canal duplication in a 6-year-old child.
AB  - A 6-year-old girl with an anal deformity had been complaining of pruritus around
      the anus. A small pit at 6 o'clock was diagnosed as an anal duplication.
      Fistulography showed a 0.5-cm-depth fistula without communication to the rectum.
      A 1.5-cm diameter presacral mass was shown on computed tomography. There was no
      sacral anomaly. At fistulectomy, the fistula contained mucous, yellow-white
      fluid. The base was enlarged, probably because of inflammation, but was resected
      without any invasion of the rectum. Histology showed squamous epithelium on the
      surface of the fistula and columnar epithelium and goblet cells in the base,
      which confirmed the diagnosis of an anal-canal duplication.

PMID- 11956799
TI  - Four cases of desmosis coli: severe chronic constipation, massive dilatation of
      the colon, and hypoperistalsis due to of changes in the colonic connective-tissue
      net.
AB  - We present four patients 5, 10, 12, and 17 years of age, each with a long history
      of severe constipation and hypoperistalsis of the gut. Three had partial or total
      resection of the colon, all had enterostomies, and only one maintains normal
      bowel function after reanastomosis. We report the clinical courses, radiologic
      findings, and operative procedures for all four cases. Preoperative full
      thickness biopsies and the resected colon specimens revealed a complete or
      incomplete lack of the mesh network of collagen. The connective-tissue layer
      between the circular and longitudinal muscles was missing. Contrary to
      expectations, the enteric nervous system (ENS) was normal or near-normal in the
      affected areas. Hypo- and dysganglionosis was found additionally in some proximal
      segments of colon and/or small bowel. This combination of clinical symptoms and
      pathological findings is called desmosis of the colon with reference to a working
      hypothesis in a preliminary report by Meier-Ruge in 1998. Aplastic or hypoplastic
      desmosis may be the reason for the disturbed gut motility. Histologic examination
      should thus not only exclude changes of the ENS.

PMID- 11956800
TI  - True duplicate bladder exstrophy: a case report.
AB  - True duplicate exstrophy is a rare and interesting congenital anomaly. We are
      adding a case to the previously reported seven cases in the world literature.

PMID- 11956801
TI  - Scrotal dog bite in an infant.
AB  - An unusual case of scrotal trauma along with loss of the right testis due to a
      bite by a stray dog in an infant is reported in view of its extreme rarity.

PMID- 11956802
TI  - Posterior sagittal approach for treatment of presacral masses in infancy.
AB  - There are very few reports on the surgical management of presacral masses (PSM)
      via a posterior sagittal (PS) approach. Between 1994 and 2000, we followed five
      girls who had been operated upon for PSMs via a PS approach. The mean age was
      28.8 +/- 16.6 months (6-48 months). The mean follow-up was 3 +/- 1.6 years (1-5
      years). Although two patients had yolk-sac tumors, all patients are still alive.
      We believe that this is a safe and satisfactory method for resection of PSMs.

PMID- 11956803
TI  - Neural-tube defect in dizygotic twins.
AB  - Despite the strong association between twinning and neural-tube defects (NTD),
      concordance of twins with NTDs is very rare. A case of concordant NTDs in
      dizygotic twins is reported in view of its extreme rarity.

PMID- 11956804
TI  - Surgical treatment of vascular malformations of the extremities in children and
      adolescents.
AB  - The treatment of vascular malformations (VM) of the extremities is controversial.
      Six patients with large, localized, symptomatic VMs of the extremities underwent
      surgical excision. In five cases abnormal vessels were apparent under the skin;
      in two of these there was also red discoloration of the skin secondary to skin
      involvement. Magnetic resonance imaging was the most helpful imaging modality in
      evaluating these patients. Subfascial resection was performed in five cases.
      Muscle was involved in four patients and was removed in all four cases. At follow
      up, there was improvement in symptoms and function with no clinically apparent
      recurrence an average of 30 months following the operation. There was improvement
      in pain intensity from an average of 4.3 on a scale of 1 to 10 before surgery to
      1.3 after surgery. Surgical excision of localized VMs that are extensive and
      include fascia and muscle, as appropriate, can successfully improve pain and
      function without evidence of recurrence at 1 to 5 years of follow-up.

PMID- 11956805
TI  - Glove-finger dressing in paediatric hypospadias.
AB  - Dressing post-operative hypospadias using a glove finger is technically easy to
      apply, inspect, and remove; gives uniform compression; is cheap and easily
      available; prevents contamination; and does not slip like ordinary dressings.

PMID- 11956806
TI  - Identification of neuromuscular synergies in natural upper-arm movements.
AB  - In this paper we study a natural upper-arm movement composed of sequential phases
      of reaching, grasping, and retrieval in the horizontal plane; in the present
      context, natural means that the spatiotemporal constraints active in the
      execution of the movement are low. The proposed method of quantitative analysis,
      which is applied to data obtained from healthy subjects, combines quantification
      of arm kinematics and kinesiologic electromyography assessment of neuromuscular
      control for each subject; to this aim, we propose using factor analysis. Despite
      the existence of a time-profile invariance of velocity traces, the identified
      factors may differ in the muscles that load on them; the interpretation is that
      different neuromuscular synergies are involved in the execution of the movement,
      which leads to cluster the subjects into two distinct groups. Compared with group
      2 subjects, group-1 subjects present a more lateral hand path direction and a
      less smooth hand trajectory in their approach to the grasped object. To explain
      the identified factors and the kinematic findings, it is hypothesized that the
      feedforward motor commands involved in trajectory planning are different.

PMID- 11956807
TI  - Pathological tremors as diffusional processes.
AB  - Two types of pathological tremors, essential and Parkinsonian, are studied using
      dynamical systems theory. It is shown that pathological tremors can be
      characterized as diffusional processes. The time-scale range for the diffusional
      scaling law to be valid starts from about one to several tens of the mean
      oscillation period. This time-scale range contrasts sharply with the predictable
      time scale for deterministic chaos, which is usually only a small fraction of the
      mean oscillation period. The diffusions in pathological tremors are usually
      anomalous. A number of quantities are designed to characterize the diffusions in
      the tremor. Their relevance to potential clinical applications is discussed. It
      is argued that in order to discriminate between Parkinsonian and essential
      tremors, quantities not of purely dynamical origin may be more useful, since
      purely dynamical quantities emphasize more the dynamical similarities between the
      two types of tremors.

PMID- 11956808
TI  - The functional sense of central oscillations in walking.
AB  - Rhythmic motor output is generally assumed to be produced by central pattern
      generators or, more specific, central oscillators, the rhythmic output of which
      can be entrained and modulated by sensory input and descending control. In the
      case of locomotor systems, the output of the central system, i.e., the output
      obtained after deafferentation of sensory feedback, shows many of the temporal
      characteristics of real movements. Therefore the term fictive locomotion has been
      coined. This article concentrates on a specific locomotor behavior, namely
      walking; in particular walking in invertebrates. In contrast to the traditional
      view, an alternative hypothesis is formulated to interpret the functional sense
      of these central oscillations which have been found in many cases. It is argued
      that the basic function of the underlying circuit is to avoid cocontraction of
      antagonistic muscles. Such a system operates best with an inherent period just
      above the maximum period observed in real walking. The circuit discussed in this
      article (Fig. 2) shows several properties in common with results described as
      "fictive walking". It furthermore could explain a number of properties observed
      in animals walking in different situations. According to this hypothesis, the
      oscillations found after deafferentation are side effects occurring in specific
      artificial situations. If, however, a parameter called central excitation is
      large enough, the system can act as a central oscillator that overrides the
      sensory input completely.

PMID- 11956809
TI  - Dissociating ocular dominance column development and ocular dominance plasticity:
      a neurotrophic model.
AB  - Recent experimental data indicate that both neurotrophic factors (NTFs) and
      intracortical inhibitory circuitry are implicated in the development and
      plasticity of ocular dominance columns. We extend a neurotrophic model of
      developmental synaptic plasticity, which previously failed to account correctly
      for the differences between monocular deprivation and binocular deprivation, and
      show that the inclusion of lateral cortical inhibition is indeed necessary in
      understanding the effects of visual deprivation in the model. In particular, we
      argue that monocular deprivation causes a differential shift in the balance
      between inhibition and excitation in cortical columns, down-regulating NTFs in
      deprived-eye columns and up-regulating NTFs in undeprived-eye columns; during
      binocular deprivation, however, no such shift occurs. We thus postulate that the
      response to visual deprivation is at the level of the cortical circuit, while the
      mechanisms of afferent segregation are at the molecular or cellular level. Such a
      dissociation is supported by recent experimental work challenging the assumption
      that columnar organisation develops in an activity-dependent, competitive
      fashion. Our extended model also questions recent attempts to distinguish between
      heterosynaptic and homosynaptic models of synaptic plasticity.

PMID- 11956810
TI  - Blind noise reduction for multisensory signals using ICA and subspace filtering,
      with application to EEG analysis.
AB  - In many applications of signal processing, especially in communications and
      biomedicine, preprocessing is necessary to remove noise from data recorded by
      multiple sensors. Typically, each sensor or electrode measures the noisy mixture
      of original source signals. In this paper a noise reduction technique using
      independent component analysis (ICA) and subspace filtering is presented. In this
      approach we apply subspace filtering not to the observed raw data but to a
      demixed version of these data obtained by ICA. Finite impulse response filters
      are employed whose vectors are parameters estimated based on signal subspace
      extraction. ICA allows us to filter independent components. After the noise is
      removed we reconstruct the enhanced independent components to obtain clean
      original signals; i.e., we project the data to sensor level. Simulations as well
      as real application results for EEG-signal noise elimination are included to show
      the validity and effectiveness of the proposed approach.

PMID- 11956811
TI  - Bayesian reconstruction of sound localization cues from responses to random
      spectra.
AB  - The directionally sensitive acoustics of the pinnae enable humans to perceive the
      up-down and front-back direction of sound. This mechanism complements another,
      independent mechanism that derives sound-source azimuth from interaural
      difference cues. The pinnae effectively add direction-dependent spectral notches
      and peaks to the incoming sound, and it has been shown that such features are
      used to code sound direction in the median plane. However, it is still unclear
      which of the pinna-induced features play a role in sound localization. The
      present study presents a method for the reconstruction of the spatially relevant
      features in the spectral domain. Broadband sounds with random spectral shapes
      were presented in rapid succession as subjects made saccadic eye movements toward
      the perceived stimulus locations. The analysis, which is based on Bayesian
      statistics, indicates that specific spectral features could be associated with
      perceived spatial locations. Spectral features that were determined by this
      psychophysical method resemble the main characteristics of the pinna transfer
      functions obtained from acoustic measurements in the ear canal. Despite current
      experimental limitations, the approach may prove useful in the study of
      perceptually relevant spectral cues underlying human sound localization.

PMID- 11956812
TI  - Computer simulation of the motoneuron pool-muscle complex. I. Input system and
      motoneuron pool.
AB  - The aim of the present study was to simulate the input system and the motoneuron
      (MN) pool of the MN pool-muscle complex (MNPMC). Input fibers, which can
      originate from command centers in the central nervous system or from sensory
      organs, activate the MN pool. They generate sequences of action potentials, the
      frequency of which is proportional to a time-dependent activation factor (which
      is an input to the model). Different connection patterns between the input fibers
      and motor units (MUs) are allowed. For simplicity and since no precise
      experimental data are available, 70 input fibers and 4 boutons per fiber and MN
      are simulated (this corresponds approximately to the monosynaptic group-Ia input
      of the cat medial gastrocnemius muscle). Each bouton generates the same
      conductance change in the postsynaptic membrane. The MNs are modeled with a
      single compartment and a homogeneous membrane. According to experimental data,
      the membrane leakage conductance and capacitance are MU dependent. Since the
      precise relation is unknown: (a) the computed relation between MU contraction
      force and the MN leakage conductance was taken from a steady-state MNPMC model,
      and (b) the capacitance was assumed to be proportional to the leakage
      conductance. The MN membrane includes time- and voltage-dependent ionic channels
      (fast and slow K(+) and low- and high-threshold Ca(2+) channels). The density and
      time constant of the slow K(+) channels and the density of the Ca(2+) channels
      were fitted to approximate afterhyperpolarization characteristics and frequency
      injected current relations of type-identified cat MNs. If the membrane reaches a
      voltage threshold the MNs generate action potentials, which were simulated by
      voltage pulses. The activation of the MN pool of the human first dorsal
      interosseus muscle was simulated with injected and synaptic currents in order to
      illustrate the size principle, synaptic noise, and other features of muscle
      activation. It is concluded that the present model reproduces the main properties
      of the input-output relations of different MN types within a muscle. Together
      with the simulation of the muscle force and the surface EMG, which will be
      published in subsequent papers, it will be a powerful tool for reproducing
      experiments on the motor system and investigating functional mechanisms of motor
      control.

PMID- 11956813
TI  - Genes involved in hepatocellular carcinoma: deregulation in cell cycling and
      apoptosis.
AB  - Hepatocellular carcinoma (HCC) accounts for 80-90% of liver cancers and is one of
      the most frequent carcinomas throughout the world. The disease is more prevalent
      in parts of Africa and Asia than in North and South America and Europe, with a
      strong etiological association with viral hepatitis, hemochromatosis, known liver
      (hepatic) carcinogens, and toxins (mycotoxins). Clinical and molecular medical
      analyses have yielded a considerable amount of information about liver
      carcinogenesis. Many genes undergo somatic aberrations, with a tendency to
      cluster at genes involved in cell cycle regulation, in the p53 and Wnt/catenin
      pathways of signal transduction and cellular adhesion, and in the TGF-beta/IGF
      axis. Since HCC may arise both in liver cirrhosis and in noncirrhotic liver, one
      may speculate that different hepatocarcinogenetic pathways exist. Recent results
      of high-output gene analysis using cDNA microarrays support the idea of different
      genetic alterations in HCC with or without cirrhosis.

PMID- 11956814
TI  - Value of thyroid transcription factor-1 and surfactant apoprotein A in the
      differential diagnosis of pulmonary carcinomas: a study of 109 cases.
AB  - Thyroid transcription factor-1 (TTF-1) and surfactant apoprotein A (SP-A) belong
      to tissue-specific markers expressed in the normal respiratory epithelium. Both
      proteins are expressed in some lung carcinomas, and they have potential
      diagnostic use. We performed an immunohistochemical study on 109 tumors to
      determine the usefulness of monoclonal SP-A (PE-10) and TTF-1 (8G7G3/1)
      antibodies in distinguishing primary and metastatic lung carcinomas ( n=54) from
      a broad spectrum of nonpulmonary tumors ( n=55). An immunoperoxidase method using
      a streptavidin-biotin kit was applied on paraffin sections. We found positive
      results for TTF-1 and SP-A in 75% and 46% of pulmonary adenocarcinomas and in 50%
      and 25% of pulmonary non-neuroendocrine large cell carcinomas (LCCs),
      respectively. Small cell lung carcinomas were TTF-1 positive in 89% of cases and
      completely negative for SP-A. Squamous cell carcinomas and carcinoid tumors were
      negative for both proteins. In the group of nonpulmonary tumors, TTF-1 was
      detected in 8 of 11 thyroid carcinomas and SP-A in 1 of 6 colorectal carcinomas.
      Other tumors, including seven cases of pleural mesothelioma, were negative for
      both TTF-1 and SP-A. The expression of both antibodies was independent of primary
      and metastatic sites of the tumor. We observed a significant decrease of SP-A
      immunoreactivity in poorly differentiated lung adenocarcinomas. The combination
      of anti-TTF-1 with anti-SP-A does not increase the diagnostic usefulness of TTF-1
      alone. Because of its diagnostic utility TTF-1 should be added to a panel of
      antibodies used for assessing tumors of unknown origin.

PMID- 11956815
TI  - Beta-catenin expression and allelic loss at APC in sporadic colorectal
      carcinogenesis.
AB  - beta-catenin is involved in E-cadherin-mediated cell adhesion, intracellular
      signal transduction, and also interacts with adenomatous polyposis coli (APC)
      protein. We previously found that 31% of colorectal adenomas and 84% of
      carcinomas showed reduced membranous staining of beta-catenin, while 46% of
      adenomas and 79% of carcinomas displayed beta-catenin nuclear expression.
      Importantly, a reciprocal relationship between reduced membranous and increased
      nuclear beta-catenin expression was demonstrated in the development from adenoma
      to carcinoma. To clarify whether this relates to an abnormality of the APC gene (
      APC), we have now studied allele loss in microdissected tissues from 74 adenomas
      and 21 carcinomas (sporadic cases, previously immunostained for beta-catenin) by
      analysis of the microsatellites D5S346, D5S82 and D5S299. Fifty-five tumors
      (57.8%) showed allele loss at APC (no difference between adenomas and
      carcinomas). Thirty-one of these 55 (31/55, 56.4%) displayed both increased
      nuclear localization and reduced membranous staining of beta-catenin, and
      thirteen tumors (13/55, 23.6%) manifested either nuclear expression without
      changes in membranous expression or reduced membranous staining without nuclear
      expression (9 and 4 cases, respectively), while 11 (11/55, 20.0%) preserved
      normal membranous expression. Adenomas and carcinomas showing both nuclear and
      reduced membranous expression of beta-catenin, compared with those with normal
      membranous expression, tended to show allele loss ( P<0.01). In addition, 24
      (24/95, 25.6%) tumors showed a change in the pattern of beta-catenin expression,
      but did not exhibit allele loss. These results suggest that although there may be
      a number of mechanisms responsible for changes in beta-catenin expression in
      colorectal tumors, dysfunction of APC may be the major cause of this phenomenon.

PMID- 11956816
TI  - Different roles of p53 between Epstein-Barr virus-positive and -negative gastric
      carcinomas of matched histology.
AB  - To clarify the role of p53 in the development of Epstein-Barr virus (EBV)
      associated gastric carcinoma, we examined DNA-ploidy pattern, the
      immunoreactivity of p53, p21(WAF1) and Ki-67 and the incidence of mitosis and
      apoptosis in EBV-positive and -negative gastric carcinomas of similar histology:
      a lace pattern and/or gastric carcinoma with lymphoid stroma. There was no
      significant difference in DNA-ploidy pattern, Ki-67 index or frequencies of
      mitosis and apoptosis between the two groups. In deeply invasive tumours
      (involving the muscularis propria or deeper), p53-positive ones were rare in the
      EBV-encoded small RNA (EBER)-positive group and very common in the EBER-negative
      group, while in superficial tumours, around one-half of them were p53-positive in
      both groups. In p53-positive superficial tumours, p21(WAF1)-positive ones
      accounted for 80% in the EBER-positive group and were scarce in the EBER-negative
      group. It is thus possible that p53 immunoreactivity reflects the overexpression
      of wild-type p53 and the stabilization of mutant p53 in the EBER-positive and 
      negative groups, respectively. The role of p53 in tumour development seems to be
      smaller in EBER-positive than in -negative gastric carcinomas.

PMID- 11956817
TI  - High incidence of B-cell monoclonality in follicular gastritis: a possible
      association between follicular gastritis and MALT lymphoma.
AB  - Many studies have indicated a close association between gastric mucosa-associated
      lymphoid tissue (MALT) lymphoma and Helicobacter pylori ( Hp) infection.
      Follicular gastritis (FG), a rare type of gastritis, is also closely associated
      with Hp infection and histologically similar to MALT lymphoma. However, there are
      few studies investigating the relationship between FG and MALT lymphoma. To
      clarify the issue, we examined the B-cell monoclonality in FG by immunoglobulin
      heavy chain (IgH) gene rearrangement. Seventy FG patients (all Hp-positive, 23
      males and 47 females, median age 33 yr) were investigated; 70 age-and gender
      matched non-FG Hp-positive controls and 24 non-FG Hp-negative controls were also
      examined. Two gastric biopsies, one from the antrum and one from the corpus, were
      obtained from each patient. DNA was extracted from formalin-fixed, paraffin
      embedded biopsy specimens. IgH gene rearrangement was examined by semi-nested
      polymerase chain reaction (PCR). In the antral mucosa, monoclonal B-cell
      populations were detected in 19 (32%) of 60 FG, in 6 (10%) of 60 Hp-positive
      controls, and in none of 20 Hp-negative controls. In the corporal mucosa,
      monoclonal B-cell populations were detected in 14 (30%) of 47 FG, in 6 (11%) of
      54 Hp-positive controls, and in none of 20 Hp-negative controls. The incidence of
      monoclonal B-cell populations in the FG patients was higher than in both Hp
      positive and Hp-negative controls ( P<0.05). The monoclonal B-cell populations
      disappeared after successful Hp eradication in 8 of 8 FG patients examined. These
      data suggest that FG may be strongly associated with MALT lymphoma, and that Hp
      eradication therapy may be indicated in FG.

PMID- 11956818
TI  - Beta-catenin mutations in sporadic fundic gland polyps.
AB  - Fundic gland polyp (FGP) is the most common gastric polyp. It occurs sporadically
      or in association with familial adenomatous polyposis (FAP). FAP patients carry
      germline mutations of the adenomatous polyposis coli (APC) gene, and previous
      studies have revealed frequent somatic mutations of the APC gene in FGPs
      associated with FAP. Although inactivation of the APC gene contributes to
      histogenesis of FGPs associated with FAP, this rarely happens in sporadic cases.
      Loss of the APC gene promotes abnormal accumulation of beta-catenin, and mutation
      of GSK-3 beta phosphorylation sites in the beta-catenin gene can have a similar
      effect. To elucidate the contribution of beta-catenin gene mutation to the
      histogenesis of sporadic FGP, we analyzed beta-catenin gene mutation in exon 3 in
      45 FGP lesions obtained from 35 patients. Somatic mutations were found in 29
      lesions: 28 were missense mutations and one was an in-frame deletion. All of the
      missense mutations were confined to the former two serine residues of the GSK-3
      beta phosphorylation sites and their flanking residues (codons 32, 33, 34, 37).
      Analysis in cases with multiple FGPs revealed a different mutation in each
      lesion, indicating their multicentric origin. Therefore, a significant proportion
      of sporadic FGPs have genetic alterations involving beta-catenin stabilization,
      as did FAP-associated FGPs.

PMID- 11956819
TI  - Localization of a specific germ cell marker, DAZL1, in testicular germ cell
      neoplasias.
AB  - DAZ-like 1( DAZL1) is a germ cell-specific protein expressed in both male and
      female gonads. The DAZL1 gene, which maps to chromosome 3 in humans, is an
      autosomal homologue to the Deleted in AZoospermia ( DAZ) gene(s) located on the Y
      chromosome. We studied the expression of DAZL1 by means of immunohistochemistry
      in order to determine its distribution among testicular germ cell neoplasias and
      among the intratubular lesions in their vicinity. Our results demonstrated that
      expression of DAZL1 protein was consistently observed in scattered cells in all
      intratubular germ cell neoplasias (IGCN) of the unclassified type, as well as in
      some of the intratubular seminomas. Foci of DAZL1 immunopositive cells were
      detected in pure seminomas, while single immunopositive cells were dispersed in
      the seminomatous component of mixed germ cell neoplasias. All the nonseminomatous
      components were negative for DAZL1 expression. These findings demonstrate an
      antigenic heterogeneity of seminoma cells. The localization of a specific germ
      cell protein, DAZL1, in the putative ontogenic progenitor, IGCN, and in their
      putative derivative, seminoma, provides further support for the hypothesis that
      IGCN is the precursor of germ cell neoplasias.

PMID- 11956820
TI  - Secondary solid neoplasms of the prostate: a clinico-pathological series of 51
      cases.
AB  - The incidence, presentation, and macroscopic and histological features of
      secondary solid neoplasms of the prostate gland are described with reference to
      their differential diagnoses. A continuous series of autopsy and surgical cases
      from the Royal London Hospital from 1907 to the present yielded a total of 51
      secondary neoplasms involving the prostate: 24 at post-mortem examination and 27
      surgical specimens. The histology of these specimens was re-examined. In 34
      cases, tumour reached the prostate by direct spread: 29 from the bladder and 5
      from the rectum. The most common primary sites of metastases to the prostate were
      lung (eight cases) and pancreas (two cases). There were isolated examples of
      metastases from the bladder, rectum, skin (malignant melanoma), breast, eye
      (malignant melanoma), adrenal cortex and gallbladder. Secondary neoplasms
      represented 2.1% of all neoplasms in surgical specimens, a similar proportion of
      the total number of malignant solid neoplasms as secondary tumours at other sites
      in the genitourinary tract. The patients were usually symptomatic, presenting
      with prostatism, haematuria or pelvic pain, almost always in those with widely
      disseminated disease.

PMID- 11956821
TI  - Crohn's disease of the appendix.
AB  - Although appendectomy is often the first surgical procedure in patients with
      Crohn's disease (CD), only few data exist on appendiceal CD. The aim of this
      study was to analyze appendices of CD patients undergoing surgery. We analyzed
      149 specimens from consecutive patients with CD who underwent primary right
      ileocolonic or (sub)total colonic resection. The appendix was present in 90
      resection specimens. Histologic findings were compared with those of 180 age and
      sex matched controls. Thirty-six appendices showed histologic signs of CD (40%):
      A transmural inflammation was found in 24 cases (67%), and a mucosal inflammation
      in 12 cases (33%). Histologic hallmarks of mucosal involvement were focal or
      discontinuous inflammation with crypt distortion and a histiocytic and
      lymphocytic predominant inflammation. Furthermore, epitheloid granulomas and
      erosions or ulcers with abundant histiocytes at the lesions base were observed.
      In comparison to controls luminal obliteration was significantly overrepresented
      in CD whereas acute phlegmonous appendicitis was underrepresented ( P<0.01).
      Patients with CD of the appendix showed a more widespread colonic involvement
      than those without ( P<0.01). This study shows that CD of the appendix exhibits
      specific histologic features that allow a differentiation from non-CD-associated
      appendicitis. CD-associated appendicitis is a frequent event, probably signifying
      a more widespread colonic involvement.

PMID- 11956823
TI  - Intracellular oxidative modification of low density lipoprotein by endothelial
      cells.
AB  - We investigated intracellular oxidative modification of low density lipoprotein
      (IOM-LDL) by endothelial cells (ECs) and the role of ferritin in this process.
      IOM-LDL was examined by immunocytochemistry with an anti-oxidized
      phosphatidylcholine antibody and by lipid peroxidation assay. Incubation of LDL
      treated ECs (human umbilical vein endothelial cells, passage 3) with ferritin
      produced cytoplasmic immunostain with the antibody, especially in large or giant
      ECs, and the formation of thiobarbituric acid-reactive substance (TBARS) in these
      cells. These observations suggest that ECs can perform IOM-LDL. Incubation with
      the iron chelator deferoxamine or pretreatment of LDL-treated ECs with
      deferoxamine suppressed ferritin-induced IOM-LDL by greater than 60%.
      Antioxidants dimethylsulphoxide and butylated hydroxytoluene markedly inhibited
      IOM-LDL, but mannitol did so only mildly. Catalase and superoxide dismutase had
      little or no effect on IOM-LDL. Apoferritin substituted for ferritin did not
      induce IOM-LDL. Our data suggest that IOM-LDL is mediated by intracellular
      hydroxyl radical formation, which is catalyzed mainly by free iron released from
      ferritin, and that ECs contribute to the development of atherosclerosis via IOM
      LDL.

PMID- 11956822
TI  - Calponin and h-caldesmon expression in atypical fibroxanthoma and superficial
      leiomyosarcoma.
AB  - To evaluate smooth muscle differentiation, myogenic markers [desmin, alpha-smooth
      muscle actin (SMA), and muscle-specific actin (HHF35)] have been widely used.
      Calponin and h-caldesmon, which are cytoskeleton-associated actin-binding
      proteins, have been reported to be more specific myogenic markers, especially
      since myofibroblasts express a small amount of h-caldesmon. Atypical
      fibroxanthoma (AFX) occurs in the sun-exposed skin of the elderly and follows a
      benign clinical course. Histologically, AFX, which is a pleomorphic spindle cell
      tumor and considered to be a superficial variant of malignant fibrous
      histiocytoma, also mimics leiomyosarcoma. AFX has been thought to differentiate
      along pathways with fibrohistiocytic and myofibroblastic phenotypes. AFX ( n=10),
      superficial leiomyosarcoma (S-LMS) ( n=17) and benign fibrous histiocytoma (BFH)
      ( n=17) were analyzed for myofibroblastic and smooth muscle differentiation
      immunohistochemically from the viewpoint of comparison. AFX and BFH showed
      immunoreactivities respectively for calponin (3/10, 11/17), desmin (3/10, 1/17),
      SMA (3/10, 13/17), and HHF35 (1/10, 5/17), but failed to express h-caldesmon
      (0/10, 0/17). S-LMS had a high immunoreactive rate of calponin (17/17), desmin
      (13/17), SMA (16/17), and HHF35 (16/17), while also expressing caldesmon (11/17).
      The results reveal that AFX and BFH have immunoreactivities for several myogenic
      markers, with myofibroblastic differentiation (calponin: +/-, h-caldesmon: -),
      but without the smooth muscle differentiation seen in S-LMS (calponin:+, h
      caldesmon: +/-). In addition, calponin and h-caldesmon are considered to be
      useful markers for distinguishing AFX from S-LMS.

PMID- 11956824
TI  - Diffuse (or multinodular) follicular variant of papillary thyroid carcinoma: a
      clinicopathologic and immunohistochemical analysis of ten cases of an aggressive
      form of differentiated thyroid carcinoma.
AB  - In an attempt to advance and improve the characterization of the so-called
      diffuse follicular variant of papillary thyroid carcinoma (diffuse FVPTC) we
      studied a series of 59 thyroid carcinomas consecutively treated in a specialized
      center. The clinicopathologic and some of the immunohistochemical characteristics
      (uPA-R, Lewis X, Sialyl Lewis X, and MIB-1) of ten cases of FVPTC displaying a
      multinodular or diffuse pattern of growth, and histologic features similar to
      those previously described in diffuse FVPTC, were compared with those of common
      papillary thyroid carcinoma (PTC, 25 cases) and common FVPTC (8 cases). Cases of
      diffuse FVPTC differed significantly from common PTC and FVPTC in targeting
      younger patients and in exhibiting a prevalence of multicentricity, extrathyroid
      extension, nodal metastasis, and vascular invasion. Immunohistochemically,
      diffuse FVPTC cases were characterized by the overexpression of uPAR and sialyl
      Lewis X. No differences were observed regarding MIB 1 immunoreactivity.
      Regardless of the term used to designate the multicentric, invasive form of FVPTC
      (diffuse or multinodular FVPTC) it is crucial to acknowledge the existence of
      cases of FVPTC with a guarded prognosis that should be distinguished from the
      classic, uninodular form of FVPTC.

PMID- 11956825
TI  - Classification of cell lineage and anatomical site, and prognosis of extranodal T
      cell lymphoma -- natural killer cell, cytotoxic T lymphocyte, and non-NK/CTL
      types.
AB  - Due to their minority among the non-Hodgkin lymphomas, classification of
      extranodal T-cell lymphomas, including those of the natural killer (NK) cell
      type, has long been controversial and unclear, and the clinical outcome is not
      well clarified. Recently, new well-defined disease entities have been described
      based on tumor cell biology combined with anatomical site, clinical features,
      Epstein-Barr virus (EBV) status, and cell lineage as determined by
      immunophenotype and genotype. Cytological features are usually not specific, and
      there are no morphologic correlates with the classification of extranodal T/NK
      cell lymphomas. From a human T-cell lymphotropic virus type 1 (HTLV-1) endemic
      area in Japan, we report here the analysis of 144 cases of extranodal T-cell
      lymphoma, from which fresh tissues were available. As the clinicopathological
      features were known, we simply reclassified the cases according to cell lineage
      and anatomical site. The extranodal T-cell lymphomas were classified into three
      types on the basis of cell lineage: (1) natural killer cell (NK) type [sCD3-,
      CD56+, T-cell receptor gene (TCR) germline], (2) cytotoxic T lymphocyte (CTL)
      type [sCD3+, TIA-1+, TCR rearranged, CD8+/-, CD4-/+], and (3) non-NK/CTL type
      [sCD3+, TIA-1-, TCR rearranged, CD4+/-, CD8-/+]. In addition to cell lineage, the
      anatomical site and clinical features were added for subclassification. NK type
      tumors (35 cases) included the lymphoblastic type, nasal/nasal-type NK lymphoma,
      and NK leukemia. The CTL type (46 cases) included anaplastic large cell lymphoma
      (ALCL), cutaneous type, intestinal, gamma delta T-cell type, and an unspecified
      type. The non-NK/CTL type (63 cases) included adult T-cell leukemia/lymphoma
      (ATLL), mycosis fungoides (MF), and an unspecified type. With the exception of
      ATLL and MF, most extranodal T-cell lymphomas had a cytotoxic phenotype of NK
      type or CTL type and were often associated with EBV infection. MF and the
      unspecified type within the non-NK/CTL tumors, with the exception of ATLL, had a
      favorable prognosis. However, NK and CTL types, with the exception of ALCL, were
      associated with a poor prognosis. Our results indicate that anatomical site and
      cell lineage are useful predictors of clinical outcomes of extranodal T-cell
      lymphomas.

PMID- 11956826
TI  - Immunohistomorphologic and molecular cytogenetic analysis of a carcinosarcoma of
      the urinary bladder.
AB  - Carcinosarcomas of the urinary bladder are malignant biphasic tumors with an
      epithelial and a spindle cell component. For the histogenesis of the two
      components, a biclonal and a monoclonal origin are discussed. We present the
      immunomorphology and molecular cytogenetics of such a case. The immunohistology
      of biopsies of the urinary bladder revealed a poorly differentiated urothelial
      carcinoma (GIII) and a co-existing pleomorphic, spindle cell leiomyosarcoma
      (GIII). The two components were microdissected and further analyzed for gains and
      losses of chromosomal material using comparative genomic hybridization. In
      addition, loss of heterozygosity analyses were included. The tumor components
      revealed as overlapping core aberrations losses on the short arm of chromosome 9
      and on the long arm of chromosome 11. However, both components showed additional
      aberrations exclusively detected in one of the components. The occurrence of
      overlapping aberrations strongly argues for a monoclonal origin of this tumor
      with a common ancestor. The additional aberrations of the components point to an
      independent and divergent course of tumor progression in both components.

PMID- 11956827
TI  - Serous oligocystic and ill-demarcated adenoma of the pancreas.

PMID- 11956828
TI  - Primary neuroendocrine (Merkel cell) carcinoma of the nipple.

PMID- 11956829
TI  - Focal nodular hyperplasia lacking some key histopathological features making the
      diagnosis difficult.

PMID- 11956834
TI  - Muscle fiber-type distribution pattern in the human cricopharyngeus muscle.
AB  - Our previous studies described that the human cricopharyngeus (CP) is composed of
      two neuromuscular compartments (NMCs), horizontal and oblique. The present study
      was designed to explore the differences in muscle fiber-type distribution between
      the NMCs within the human CP and to examine the oxidative capacity of the muscle
      fibers. Seven adult human CP muscles obtained from autopsies were stained for
      myofibrillar ATPase, reduced nicotinamide adenine dinucleotide tetrazolium
      reductase (NADH-TR), and succinic dehydrogenase (SDH) to analyze enzyme
      histochemical fiber-type characteristics. Notable findings obtained from this
      study are as follows: (1) Different NMCs within the human CP contained different
      percentages of muscle fiber types. The horizontal CP (CPh) contained more slow
      twitch fibers than the oblique CP (CPo). (2) Each of the NMCs was dividable
      histochemically into two layers or subcompartments: a slow fiber-type inner layer
      and a relatively fast fiber outer layer. (3) As a whole, type I fibers had higher
      levels of NADH-TR and SDH than type II fibers. However, in both type I and II
      muscle fiber types, different patterns of oxidative enzyme activity were seen.
      Histochemically defined fiber layers of the CP are not seen in other mammals,
      suggesting that CP function is more specialized in humans.

PMID- 11956835
TI  - The SWAL-QOL and SWAL-CARE outcomes tool for oropharyngeal dysphagia in adults:
      III. Documentation of reliability and validity.
AB  - Advances in the measurement of swallowing physiologic parameters have been
      clinician-driven, as has the development of intervention techniques to modify
      swallowing pathophysiology. However, a critical element to determining the
      success of such efforts will be established by the patients themselves. We
      conceptualized, developed, and validated the SWAL-QOL, a 93-item quality-of-life
      and quality-of-care outcomes tool for dysphagia researchers and clinicians. With
      93 items, the SWAL-QOL was too long for practical and routine use in clinical
      research and practice. We used an array of psychometric techniques to reduce the
      93-item instrument into two patient-centered outcomes tools: (1) the SWAL-QOL, a
      44-item tool that assesses ten quality-of-life concepts, and (2) the SWAL-CARE, a
      15-item tool that assesses quality of care and patient satisfaction. All scales
      exhibit excellent internal-consistency reliability and short-term
      reproducibility. The scales differentiate normal swallowers from patients with
      oropharyngeal dysphagia and are sensitive to differences in the severity of
      dysphagia as clinically defined. It is intended that the standardization and
      publication of the SWAL-QOL and the SWAL-CARE will facilitate their use in
      clinical research and clinical practice to better understand treatment
      effectiveness as a critical step toward improving patients' quality of life and
      quality of care.

PMID- 11956836
TI  - The incidence, management, and complications of dysphagia in patients with
      medullary strokes admitted to a rehabilitation unit.
AB  - The objective of this study was to examine the frequency of dysphagia symptoms
      and related consequences in medullary stroke patients admitted to a stroke
      rehabilitation unit. A chart review of a cohort of 563 stroke patients admitted
      to a rehabilitation unit was used to identify patients with evidence of
      predominantly medullary lesions. The results of both initial and followup
      videofluoroscopic modified barium swallowing (VMBS) studies were also reviewed
      for evidence of aspiration and residuum in patients with dysphagia. Twenty of the
      563 patients (3.6%) were diagnosed with a medullary stroke. Eleven of the 20
      (55%) patients were identified clinically with dysphagia and nine had at least
      one (VMBS) study. All dysphagic patients demonstrated some degree of either
      aspiration or residuum on both initial and final swallowing studies and received
      some form of dietary modification. Comparisons between patients with and without
      dysphagia demonstrated significant differences with regard to length of hospital
      stay and the development of pneumonia (p < 0.05). More than half of the patients
      with medullary strokes presented with clinical indications of dysphagia, were
      more likely to develop aspiration pneumonia, and experienced longer hospital
      stays. Aspiration pneumonia appeared to be an early complication of stroke and
      dietary modifications did not prevent its development.

PMID- 11956837
TI  - Influence of esophageal motility on esophageal speech of laryngectomized
      patients.
AB  - After laryngectomy for treatment of cancer of the larynx, the patient may have
      vocal rehabilitation by esophageal speech. Some patients fail to achieve the
      esophageal speech due to reasons involving surgery, radiotherapy, and
      psychological alterations. Our hypothesis is that the esophageal motility
      alterations consequent to laryngectomy may be involved in the failure to achieve
      esophageal speech. Using manometry with continuous perfusion, we studied the
      esophageal motility of 25 laryngectomized patients, 10 of them able to produce
      esophageal speech and 15 unable to produce esophageal speech, and 40 asymptomatic
      normal volunteers. The lower esophageal sphincter (LES) pressure was measured by
      the rapid pull-through method and the upper esophageal sphincter (UES) pressure
      by the station pull-through method. The contractions were measured at 5, 10, and
      15 cm above the LES after the subjects performed 10 swallows with a 5-mL bolus of
      water. By comparing volunteers and laryngectomized patients, we found a lower UES
      pressure, lower amplitude of contractions, and increased percentage of
      simultaneous contractions in laryngectomized patients (p < 0.05). There was no
      difference between patients able and unable to produce esophageal speech in LES
      and UES pressure, esophageal contraction duration and velocity, or in the
      percentage of failed and simultaneous contractions. The esophageal contraction
      amplitude was lower in patients who acquired esophageal speech than in patients
      who did not (p < 0.05 at 10 cm from LES). We conclude that there are esophageal
      motility alterations in laryngectomized patients but only the decrease of
      esophageal contraction amplitude seems to be associated with the acquisition of
      esophageal speech.

PMID- 11956838
TI  - Variability in tongue movement kinematics during normal liquid swallowing.
AB  - This study sought to develop a quantitative kinematic description of tongue
      movement for liquid swallowing in a group of 12 healthy subjects. X-ray microbeam
      technology was used to track the positions of six small pellets attached to the
      tongue and jaw while subjects swallowed water at 2- and 10-mL bolus volumes. A
      feature common to all subjects was a prominent rostral movement of the dorsal
      region of the tongue. In addition, all subjects consistently increased the
      displacement and maximum speed of this tongue movement with increased bolus
      volume. However, detailed movement analysis showed a variety of tongue movement
      patterns for the group. This variability across subjects was large enough that it
      was surprisingly difficult to provide a low-dimension quantitative description of
      the tongue kinematics during liquid swallowing.

PMID- 11956839
TI  - Social and psychological burden of dysphagia: its impact on diagnosis and
      treatment.
AB  - The social and psychological impact of dysphagia has not been routinely reported
      in large studies. We sought to determine the effects of dysphagia on broad
      measures of the quality of life of patients and to explore the relationship
      between the psychological handicaps of the condition and the frequency of
      diagnosis and treatment. A total of 360 patients selected on the basis of known
      subjective dysphagia complaints, regardless of origin, in nursing homes and
      clinics in Germany, France, Spain, and the United Kingdom were interviewed using
      an established questionnaire. Qualitative interviews with a total of 28 health
      professionals were conducted to improve understanding of the patient data in the
      context of each country. Over 50% of patients claimed that they were "eating
      less" with 44% reporting weight loss during the preceding 12 months. Thirty-six
      percent of patients acknowledged receiving a confirmed diagnosis of dysphagia;
      only 32% acknowledged receiving professional treatment for it. Most people with
      dysphagia believe their condition to be untreatable; only 39% of the sufferers
      believed that their swallowing difficulties could be treated. Eighty-four percent
      of patients felt that eating should be an enjoyable experience but only 45%
      actually found it so. Moreover, 41% of patients stated that they experienced
      anxiety or panic during mealtimes. Over one-third (36%) of patients reported that
      they avoided eating with others because of their dysphagia. In a largely elderly
      population that might accept dysphagia as an untreatable part of the aging
      process, clinicians need to be aware of the adverse effects of dysphagia on self
      esteem, socialization, and enjoyment of life. Careful questioning should assess
      the impact of the condition on each patient's life, and patients should be
      educated on their choices for treatment in the context of any coexisting illness.
      Awareness of the condition, diagnostic procedures, and treatment options must be
      increased in society and among the medical profession.

PMID- 11956840
TI  - A prospective assessment of the characteristics of dysphagia in myasthenia
      gravis.
AB  - Fatigable muscle weakness is the clinical hallmark of the human autoimmune
      disease myasthenia gravis (MG). Weakness of the oropharyngeal muscles produces
      dysphagia, which continues to be a major source of morbidity in MG. In this study
      we prospectively assessed 20 patients with myasthenia gravis who described
      difficulties with swallowing. Videofluoroscopic assessment showed disordered
      swallowing in all, with abnormalities in oral, pharyngeal, and, to a lesser
      extent, oral preparatory phases. Of the 20 studied, 7 aspirated, most of whom did
      so silently. Laryngeal penetration occurred in many more patients. The
      characteristics of dysphagia in MG are described and compared with other
      neurological disorders that can produce dysphagia.

PMID- 11956841
TI  - Swallow-induced alterations in breathing in normal older people.
AB  - Respiratory parameters in 29 normal older subjects (mean age-73 years, SD = 5.7)
      were studied at rest, during single water swallows, and in continuous drinking.
      Respiration was recorded by intranasal air pressure changes and the moment of
      swallowing by pharyngoesophageal manometry. Compared with respiration at rest,
      respiratory rate increased immediately after 5 mL swallows as duration of breath
      cycles decreased from a mean of 3.8 s at rest to 3.5 s after swallowing (p =
      0.003), but regularity of respiration was maintained. Deglutition apnea showed a
      trend toward increasing duration from a median of 1.06 to 1.24 s (p = 0.096) as
      bolus volume increased from 5 to 20 mL. Oxygen saturation levels were also
      compared, with a median fall of 2% during swallowing, but with larger and
      unexplained falls in several subjects. Direction of airflow monitoring showed 91%
      of single 5 mL swallows were followed by expiration, with postswallow inspiratory
      breaths occurring in 41% of subjects. Continuous swallowing of 100 mL of water
      from a cup and straw was typically performed with a pattern of multiple swallows
      per breath, with expiration occurring after 78.5% (cup) and 63.5% (straw) of
      swallows. This definition of swallowing-induced respiratory changes in normal
      older people forms a valuable basis for future comparison with elderly dysphagic
      patients.

PMID- 11956842
TI  - Real-time remote telefluoroscopic assessment of patients with dysphagia.
AB  - Dysphagia is a serious health problem that affects persons of all ages, from the
      neonate to those of advanced age. Many smaller communities and areas with sparse
      populations do not have regular access to professionals with expertise in the
      area of oral/pharyngeal dysphagia. Telemedicine is one method by which people in
      these areas can receive quality of service. The intent of this work was to
      develop an Internet system that permits real-time, remote, interactive evaluation
      of oral/pharyngeal swallowing function. The system consists of two major
      components. The first is a PC that is located in the fluoroscopy suite of a
      hospital. The computer is connected to the fluoroscope output and is responsible
      for (1) capturing video signals, (2) converting the analog video data into
      digitized video formats of both full resolution and transmission-optimized
      resolution, (3) simultaneously transmitting the transmission-optimized video
      stream over the network while the examination is being performed, and (4) storing
      the full-resolution data as a file in local storage for later retrieval. The
      second component is the controller computer which is located at a site some
      distance from the hospital. That controller computer manages the video capture
      process at the remote hospital site, manages the transmission of the stored
      images, and is then used for video analysis. The delay between the image as it
      was captured at the remote hospital site and viewed on the controller computer in
      the Principal Investigator's (PI's) laboratory ranged from 3 to 5 s. Video
      transmission occurred over a standard T1 line.

PMID- 11956844
TI  - The Tenth Annual Meeting of the Dysphagia Research Society.

PMID- 11956845
TI  - Abstracts of Scientific Papers Presented at the Tenth Annual Dysphagia Research
      Society Meeting, Albuquerque, New Mexico, USA, October 11-13, 2001.

PMID- 11956846
TI  - Abstracts of Posters Presented at the Tenth Annual Dysphagia Research Society
      Meeting, Albuquerque, New Mexico, USA, October 11-13, 2001.

PMID- 11956849
TI  - Pediatric hemofiltration: Normocarb dialysate solution with citrate
      anticoagulation.
AB  - Fourteen children, newborn to 17 years of age, underwent continuous veno-venous
      hemofiltration with dialysis (CVVHD), using a new FDA-approved bicarbonate-based
      calcium-free dialysis solution (Normocarb) in combination with citrate
      anticoagulation. Dialysis prescription included use of the PRISMA system (Gambro,
      Lakewood, Colo., USA), with ACD-A (Baxter, Deerfield, Ill., USA) for
      anticoagulation and Normocarb (Dialysis Solution, Richmond Hills, Ontario,
      Canada) for dialysate. Diagnosis included 11 children with sepsis and 3 children
      with tumor lysis syndrome. Mean weight was 31.6+/-4.7 kg (range 3.7-62 kg) and
      average length of therapy was 11.4+/-3.7 days (range 6 h to 67 days). Length of
      circuit patency was 71.3+/-7.2 h (range 6 h to 127 h), which was influenced in
      part by a decision to change circuits at 72 h as per manufacturer's
      recommendation. No bleeding occurred. This protocol utilizes industry
      manufactured CVVHD machinery with both thermic and ultrafiltration control, with
      an effective anticoagulation protocol, and industry-produced bicarbonate
      dialysate. The use of industry machinery and solutions allows for consistent
      industrial quality assurance standards. This potentially may decrease the cost of
      therapy and minimize the risk of pharmacy errors that can occur with pharmacy
      made dialysis solutions.

PMID- 11956850
TI  - Tissue plasminogen activator for occluded peritoneal dialysis catheter.
AB  - Inadequate flow in a peritoneal catheter is a common problem in pediatric
      patients. We report the effectiveness of the intra-catheter application of tissue
      plasminogen activator for the resolution of a malfunctioning peritoneal dialysis
      catheter in a child.

PMID- 11956848
TI  - Randomized trial of tacrolimus versus cyclosporin microemulsion in renal
      transplantation.
AB  - This study was undertaken to compare the efficacy and safety of tacrolimus (Tac)
      with the microemulsion formulation of cyclosporin (CyA) in children undergoing
      renal transplantation. A 6-month, randomized, prospective, open, parallel group
      study with an open extension phase was conducted in 18 centers from nine European
      countries. In total, 196 pediatric patients (<18 years) were randomly assigned
      (1:1) to receive either Tac ( n=103) or CyA microemulsion ( n=93) administered
      concomitantly with azathioprine and corticosteroids. The primary endpoint was
      incidence and time to first acute rejection. Baseline characteristics were
      comparable between treatment groups. Tac therapy resulted in a significantly
      lower incidence of acute rejection (36.9%) compared with CyA therapy (59.1%) (
      P=0.003). The incidence of corticosteroid-resistant rejection was also
      significantly lower in the Tac group compared with the CyA group (7.8% vs. 25.8%,
      P=0.001). The differences were also significant for biopsy-confirmed acute
      rejection (16.5% vs. 39.8%, P<0.001). At 1 year, patient survival was similar
      (96.1% vs. 96.6%), while 10 grafts were lost in the Tac group compared with 17
      graft losses in the CyA group ( P=0.06). At 1 year, mean glomerular filtration
      rate (Schwartz estimate) was significantly higher in the Tac group (62+/-20
      ml/min per 1.73 m(2), n=84) than in the CyA group (56+/-21 ml/min per 1.73 m(2),
      n=74, P=0.03). The most frequent adverse events during the first 6 months were
      hypertension (68.9% vs. 61.3%), hypomagnesemia (34.0% vs. 12.9%, P=0.001), and
      urinary tract infection (29.1% vs. 33.3%). Statistically significant differences
      ( P<0.05) were observed for diarrhea (13.6% vs. 3.2%), hypertrichosis (0.0% vs.
      7.5%), flu syndrome (0.0% vs. 5.4%), and gum hyperplasia (0.0% vs. 5.4%). In
      previously non-diabetic children, the incidence of long-term (>30 days) insulin
      use was 3.0% (Tac) and 2.2% (CyA). Post-transplant lymphoproliferative disease
      was observed in 1 patient in the Tac group and 2 patients in the CyA group. In
      conclusion, Tac was significantly more effective than CyA microemulsion in
      preventing acute rejection after renal transplantation in a pediatric population.
      The overall safety profiles of the two regimens were comparable.

PMID- 11956851
TI  - Parental hypertension and 24 h-blood pressure in children prior to diabetic
      nephropathy.
AB  - In a search for predictors of nephropathy development, albumin excretion rate
      (AER), ambulatory blood pressure, and parental hypertension were assessed in 40
      type 1 diabetic patients and 27 normal siblings (age<18 years) during a 2-year
      follow-up period. A double-antibody kit and an automated device were used for
      measuring 24-h AER and ambulatory blood pressure monitoring (ABPM), respectively.
      Patients had higher 24-h and daytime diastolic blood pressure (DBP), diastolic
      load, and daytime heart rate than siblings. Patients with hypertensive parents
      had higher 24-h DBP and diastolic load than patients with normotensive parents
      and all siblings. Non-dipping was more frequent in children with hypertensive
      parents ( P<0.05). Both diabetes ( P<0.001) and parental hypertension ( P<0.05)
      had independent effects on longitudinal AER (average AER during follow-up).
      Patients with intermittent or persistent microalbuminuria showed a trend towards
      higher diastolic load ( P<0.05); the latter group had higher 24-h DBP ( P<0.01).
      Longitudinal AER correlated with 24-h DBP ( P<0.01) and maternal mean blood
      pressure ( P<0.05). Since changes in blood pressure preceded persistent
      microalbuminuria, ABPM might help to identify diabetic children prone to
      nephropathy.

PMID- 11956852
TI  - Long-term outcome of focal segmental glomerulosclerosis after Japanese pediatric
      renal transplantation.
AB  - Focal segmental glomerulosclerosis (FSGS) is known to recur in some patients
      after renal transplantation. Over a prolonged period, we followed 13 pediatric
      patients with FSGS who had undergone transplantation from living-related donors,
      analyzing risk factors for recurrent disease. Native nephrectomies were performed
      bilaterally in all patients at least 1 month prior to transplantation.
      Immunosuppressive therapy consisted of cyclosporine (CyA), mizoribine,
      prednisone, and antilymphocytic globulin or deoxyspergualin. We examined age at
      onset, time in months between diagnosis and end-stage disease (dialysis or
      transplantation), the duration of dialysis, age at transplantation, time since
      nephrectomy, doses of immunosuppressive agents, and HLA mismatch. Five patients
      (42.8%) developed recurrent disease in the graft; all showed proteinuria within
      24 h of transplantation. However, all allografts have functioned well for 34-156
      months following transplantation despite the recurrences, although 1 of these
      patients now shows proteinuria. The remaining 8 patients have had no recurrence
      for 104.6+/-30.4 months (mean+/-SD). The serum level of creatinine in patients
      with recurrence and without recurrence was 1.1+/-0.42 mg/dl and 0.98+/-0.29
      mg/dl, respectively. The interval from diagnosis to initiation of dialysis was
      significantly shorter in patients with recurrence than those without recurrence (
      P<0.05), but no other variables differed between these two groups. No recurrence
      of FSGS was observed in the protocol biopsy at 100 days after transplantation. We
      believe that CyA and native nephrectomy may limit or reverse progression of
      recurrent FSGS in renal allografts of Japanese pediatric patients, although this
      is a limited study.

PMID- 11956853
TI  - Premature acute myocardial infarction in a child with nephrotic syndrome.
AB  - We report a case of acute myocardial infarction in a nephrotic child. A 7-year
      old boy with a 4-year history of steroid-unresponsive nephrotic syndrome due to
      mesangial proliferation disease presented with acute vomiting and chest pain. An
      electrocardiogram showed ST elevation and pathological Q waves in leads
      consistent with anterior and septal myocardial infarction. Subsequent cardiac
      catheterization showed no evidence of atherosclerotic coronary artery disease,
      and thrombotic occlusion of the anterior descending coronary artery was the
      likely cause of the event. Myocardial scintigraphy showed extensive myocardial
      damage. The child had no long history of extreme hypercholesterolemia or
      hypertriglyceridemia. The case suggests that children with long-lasting nephrotic
      syndrome may be at increased risk for ischemic cardiovascular events, due to
      hyperlipidemia as well as a hypercoagulability state. The literature is reviewed
      regarding the relationship between nephrotic syndrome and the incidence of
      ischemic heart disease.

PMID- 11956854
TI  - Febrile urinary tract infection: Escherichia coli susceptibility to oral
      antimicrobials.
AB  - Empirical treatment is indicated for young children with febrile urinary tract
      infection (UTI). In this clinical setting, oral antibiotics are as safe and
      effective as intravenous therapy. The aim of this study was to investigate in
      children with febrile UTI whether there were longitudinal changes in the
      prevalence of bacteria and in the pattern of Escherichia coli susceptibility to
      oral antimicrobial agents. Two hundred and eighty-seven positive urine cultures
      from children (1 month to 12 years) with febrile UTI collected over three periods
      (1986-1989, 1990-1991, and 1997) were studied. E. coli was the most-prevalent
      microorganism in all three study-periods ( n=228). The susceptibility pattern of
      E. coli to nitrofurantoin (92%, 95%, 94%) and nalidixic acid (85%, 92%, 95%) did
      not present any statistically significant differences ( P>0.05) over time. There
      was a significant increase ( P<0.05) in E. coli susceptibility to cephalexin
      (65%, 54%, 81%). The E. coli susceptibility to trimethoprim-sulfamethoxazole
      (40%, 85%, 40%) behaved differently. Initially there was a significant rise (
      P<0.05), followed by a significant decrease ( P<0.05). Empirical oral treatment
      with nitrofurantoin or nalidixic acid can safely be started in children with
      febrile UTI seen in the Emergency Department, Hospital de Clinicas de Porto
      Alegre, Brazil.

PMID- 11956855
TI  - Right perinephric abscess: a rare presentation of ruptured retrocecal
      appendicitis.
AB  - Perinephric abscess commonly arises from rupture of an intrarenal abscess into
      the perinephric space. It rarely results from gastrointestinal pathology. We
      report two pediatric patients with retrocecal appendicitis that presented with
      perinephric abscess. A 3-year-old girl presented with high fever and right flank
      pain for more than 1 week. Ultrasonography showed a right perinephric fluid
      collection with normal renal parenchyma and collecting system. A perinephric
      abscess extending from a ruptured retrocecal appendix was diagnosed by abdominal
      computed tomographic (CT) scan. Her hospital course was complicated with empyema,
      peritonitis, and pericardial effusion. A 6-year-old girl had lower abdominal pain
      for 3 days and high fever on the day of admission. Ultrasonography showed a right
      perinephric abscess with a normal renal contour and a fecalith in the enlarged
      appendix in the right lower quadrant of the abdomen. Appendectomy and drainage of
      the perinephric abscess were performed in both cases. We suggest that a ruptured
      retrocecal appendix must be considered in cases of perinephric abscess,
      especially in patients with gas bubbles in the abscess and a normal urogenital
      appearance. Ultrasonography and abdominal CT scan are the preferred diagnostic
      tools. Prolonged antibiotics and drainage of the abscess are mandatory to
      decrease morbidity and mortality.

PMID- 11956856
TI  - Varicella vaccination in children with steroid-sensitive nephrotic syndrome.
AB  - We have studied serological and clinical response to live, attenuated varicella
      zoster virus (VZV) vaccine (Varilrix, SmithKline Beecham) in 20 patients with
      steroid-sensitive nephrotic syndrome (SSNS) in remission and 22 normal controls
      who had no history of varicella and no detectable antibody to VZV. Nephrotic
      patients included 15 boys and 5 girls, with a mean age of 4.7 years (range 2-11.4
      years). The controls were healthy age-matched children (13 girls and 9 boys).
      Seventeen patients with SSNS (85%) and 19 healthy controls (86%) seroconverted 8
      weeks after vaccination. One patient with SSNS had a relapse 20 days after
      vaccination, and 1 child in the control group had a rash. Two years after
      vaccination, antibodies to VZV were detected in 12 of 17 responders, 2 of 3 non
      responders, and 13 of 22 controls. Within 2 years of vaccination, 3 of the
      vaccine responder children with SSNS had a mild varicella infection. Two
      responder and 1 non-responder nephrotic children and 9 controls were lost to long
      term follow-up. Our results show that immunization with a single dose of VZV
      vaccine is safe and effective in children with SSNS in remission.

PMID- 11956857
TI  - Thalamic stroke secondary to straight sinus thrombosis in a nephrotic child.
AB  - A 7-year-old Chinese boy with steroid-resistant nephrotic syndrome developed
      thalamic stroke secondary to straight sinus thrombosis. He was hospitalized due
      to status epilepticus and coma. The child recovered after treatment by low
      molecular-weight heparin (LMWH) and warfarin. This case highlights the importance
      of magnetic resonance imaging with venography in the early diagnosis of cerebral
      sinus thrombosis (CST) in nephrotic children and the effectiveness of
      anticoagulation therapy in improving the neurological outcome.

PMID- 11956858
TI  - Congenital mesoblastic nephroma associated with polyhydramnios and hypercalcemia.
AB  - Congenital mesoblastic nephroma (CMN) can present with atypical clinical and
      imaging findings. A premature male neonate was born to an 18-year-old woman after
      33 weeks' gestation, which was complicated by polyhydramnios and placenta
      abruptio. A right abdominal mass was diagnosed antenatally. From the 1st day of
      life, the newborn had hypercalcemia with initially normal parathormone levels and
      polyuria for the first hours of life and normal urine output afterwards.
      Ultrasonographic study and magnetic resonance imaging of the abdomen showed at
      the upper pole of the right kidney a heterogeneous, solid, poorly defined mass,
      partially surrounded by a subcapsular fluid collection mimicking malignant
      rhabdoid tumor of the kidney. Surgical resection revealed a CMN of mixed,
      classic, and in areas, cellular type. One year after the resection, the patient
      is asymptomatic and normocalcemic. In conclusion, CMN may present with atypical
      clinical and imaging findings, necessitating an extensive work-up in order to
      exclude highly malignant renal tumors of the neonatal period.

PMID- 11956859
TI  - Hemolytic uremic syndrome due to an altered factor H triggered by neonatal
      pertussis.
AB  - We report on a previously healthy newborn suffering from severe Bordetella
      pertussis infection who developed hemolytic uremic syndrome (HUS) a few weeks
      after the onset of whooping cough, with a fatal outcome. A factor H protein with
      abnormal mobility was found in the serum of the patient as analyzed by Western
      blotting, indicating that B. pertussis infection might have triggered HUS in a
      genetically predisposed patient.

PMID- 11956860
TI  - Renal artery stenosis and aneurysmatic dilatation of arteria carotis interna in
      tuberous sclerosis complex.
AB  - Hypertension in children with neurocutaneous disorders (phacomatoses) is a well
      recognized complication of these diseases and the cause of hypertension is fairly
      specific within each group. In patients with neurofibromatosis, hypertension is
      mainly caused by renovascular disease, whereas in tuberous sclerosis (TSC)
      reasons for hypertension are renoparenchymal lesions, such as angiomyolipoma or
      cysts. We report on a girl with TSC and hypertension due to unilateral renal
      artery stenosis associated with aneurysmatic changes of internal carotid artery.
      This unusual combination of symptoms in our patient supports the importance of
      thorough and complete investigation of hypertension in children with
      phacomatoses.

PMID- 11956861
TI  - Increased apoptosis of peripheral blood lymphocytes in children with nephrotic
      syndrome.
AB  - Nephrotic syndrome is accompanied by and probably related to abnormal T
      lymphocyte function. Decreased stimulation of survival factors and increased
      levels of "dead signals" may lead to the malfunction of many cells, including
      lymphocytes. In our study, we investigated the process of apoptosis within T
      cells in children with a first attack of nephrotic syndrome (NS). We found that
      the number of apoptotic T cells is greater in these patients than in both
      children in remission from NS and in controls. The percentage of annexin-V
      fluorescein isothiocyanate (FITC)-positive CD3+ cells was 27.30+/- 12.13% in
      children with a first attack of NS, 19.22+/- 15.16% (P=0.006) in children in
      remission and 16.20+/- 6.13% (P=0.004) in controls. The percentage of annexin-V
      FITC-positive CD3+CD4+ cells was 7.35+/-7.72% in children with a first attack of
      NS, 3.80+/-3.75% (P=0.0001) in children in remission and 3.82+/-2.01% (P=0.0002)
      in controls. We conclude that abnormal number and function of T lymphocytes found
      in NS patients may be related to an increased apoptotic rate of circulating
      lymphocytes.

PMID- 11956862
TI  - Antibodies to intimin and Escherichia coli secreted proteins A and B in patients
      with enterohemorrhagic Escherichia coli infections.
AB  - Enterohemorrhagic Escherichia coli produce an attaching and effacing lesion upon
      adhering to the intestinal epithelium. Bacterial factors involved in this
      histopathology include the intimin adhesin and E. coli secreted proteins (Esps) A
      and B. In this study we investigated the serum antibody responses to recombinant
      E. coli O157:H7 intimin, EspA, and EspB by immunoblotting. Canadian patients with
      O157:H7 infection (n=10), Swedish patients with O157:H7 (n=21), non-O157 (n=18),
      or infection from which the serotype was not available (n=3), and asymptomatic
      household members (n=25) were studied and compared with Canadian (n=20) and
      Swedish controls (n=52). In Canadian patients, IgG antibodies to intimin, EspA,
      and EspB were analyzed, in Swedish patients and their household members IgA, IgG,
      and IgM antibodies to EspA and EspB were studied. Patients and household members
      mounted an antibody response to the antigens. Significantly more patients
      developed an acute response to EspB compared with controls (P<0.01 Canadian
      patients, P<0.0001 Swedish patients). EspB IgA, IgG, and IgM had a specificity of
      100%, 86%, and 86%, positive predictive value of 100%, 83%, and 81%, and
      sensitivity of 57%, 69%, and 63%, respectively, and appear to be an appropriate
      assay for the detection of EHEC infection. In cases of hemolytic uremic syndrome
      or hemorrhagic colitis this assay may be useful when a fecal strain has not been
      isolated, or in epidemics of non-O157 infection.

PMID- 11956863
TI  - Increased HLA- A*11 in Chinese children with steroid-responsive nephrotic
      syndrome.
AB  - Human leukocyte antigen (HLA) associations have been frequently reported in
      childhood steroid-responsive nephrotic syndrome (SRNS) in other populations. The
      aim of this study was to characterize the immunogenetic background of Singaporean
      Chinese patients with childhood SRNS. We determined the HLA class I (HLA- A* and
      HLA-B*) as well as class II (HLA- DRB1*, HLA- DQB1*) gene polymorphisms using the
      polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique,
      in patients with SRNS (n=64) and normal controls (n=236 for HLA- A*, n=80 for HLA
      B*, HLA- DRB1* and HLA- DQB1*). The frequency of HLA- A*11 allele was
      significantly higher in the SRNS patients compared to controls (78.1% vs 54.2%,
      respectively; relative risk, RR=3.01, Pc=0.011). However, there was no
      significant difference in the allele frequencies of HLA- B*, HLA- DRB1* and HLA-
      DQB1* between the SRNS patients and controls, unlike that in previous studies.
      Our data suggest that the immunogenetic background of Singaporean Chinese with
      childhood SRNS was different from that in other populations. As HLA- A*11 has
      been strongly associated with other autoimmune diseases, it is conceivable that
      the HLA- A*11-specific motif may play a role in the development of the abnormal T
      cell-mediated immune response that may be responsible for triggering the
      proteinuria seen in SRNS.

PMID- 11956865
TI  - Inflammatory pseudotumor of the bladder in chronic granulomatous disease.

PMID- 11956864
TI  - Clinical quiz. Loin pain haematuria syndrome.

PMID- 11956866
TI  - Fetal renal hyperechogenicity in intrauterine growth retardation.

PMID- 11956868
TI  - Cyclosporin-related nephrotoxicity in children with nephrotic syndrome.

PMID- 11956871
TI  - Recent insights into kidney diseases associated with glomerular cysts.
AB  - Glomerular cysts can exist in the context of several different kidney diseases.
      Advances in the last few years have begun to unravel the genetic bases and
      pathogenesis of some of these entities, many of which have an origin in abnormal
      development. In this review, we highlight recent insights into three types of
      disease associated with glomerular cysts: (1) mutations of the hepatocyte nuclear
      factor 1beta (HNF-1beta)in the recently described renal cysts and diabetes
      syndrome, (2) mutations of OFD1in the oral facial digital syndrome type 1 and (3)
      the role of fetal urinary tract obstruction.

PMID- 11956872
TI  - A case of post-transplant hyperparathyroidism treated with ethanol injection.
AB  - A 15-year-old boy with chronic renal failure secondary to Alport's syndrome
      underwent living-related renal transplantation from his 48-year-old father. His
      primary immunosuppressive regimen was composed of tacrolimus, mizolibine, and
      methylprednisolone. The postoperative course was satisfactory with one episode of
      mild acute rejection, treated successfully with methylprednisolone pulse therapy.
      Two months later, hypercalcemia (11.8-13.2 mg/dl) and hypophosphatemia (2.5-3.0
      mg/dl) were noted without any bone symptoms. The serum intact-parathyroid hormone
      (PTH) and serum alkaline phosphatase levels were 240 pg/ml and 2483 IU/l,
      respectively. Ultrasound studies revealed enlargement of the two parathyroid
      glands. Under the diagnosis of tertiary hyperparathyroidism, he underwent
      percutaneous ethanol injection (PEIT) into the left parathyroid gland. Although
      levels of serum calcium and phosphorus returned to normal ranges and the intact
      PTH level decreased to 95 pg/ml with the three injections, another injection was
      needed to normalize recurrent hypercalcemia 2 months later. The patient
      experienced only transient mild dysphonia and local pain after PEIT. Although
      PEIT is believed less effective than parathyroidectomy, it has some advantages
      such as applicability to high-risk patients, repeatability of treatment, low
      incidence and severity of side effects.

PMID- 11956873
TI  - Utility of hemodialysis in maple syrup urine disease.
AB  - Maple syrup urine disease (MSUD) is an inborn error of metabolism stemming from a
      deficiency in 2-ketoacid dehydrogenase and resulting in the systemic accumulation
      of branched chain amino acids (BCAAs). Affected children may suffer profound
      developmental and cognitive impairment from exposure to high levels of BCAA and
      their associated neurotoxic metabolites. Endogenous renal clearance of BCAA is
      limited and several therapeutic modalities including intensive nutritional
      regimens, exchange transfusions, peritoneal dialysis, and continuous
      hemofiltration have been utilized in neonates with MSUD, all of which have had
      varying success in reducing systemic BCAA levels. In this report, a symptomatic 7
      day-old 3-kg neonate with MSUD underwent treatment with a combination of early
      hemodialysis and aggressive enteral feedings of a metabolically appropriate
      formula. This approach results in a 75% reduction of systemic toxin levels within
      3 h. When compared to other reported modalities of therapy for symptomatic
      neonates with MSUD, this approach appears to be most efficacious. Moreover, by
      minimizing the amount of time that an affected neonate is exposed to neurotoxic
      levels of BCAAs, long-term developmental and cognitive capabilities may be
      preserved.

PMID- 11956874
TI  - Successful treatment of Aspergillus peritonitis in a peritoneal dialysis patient.
AB  - Aspergillus peritonitis is a rare, potentially fatal complication of continuous
      ambulatory peritoneal dialysis (CAPD). We report the successful treatment of
      refractory fungal peritonitis in an 8-year-old girl treated by peritoneal
      dialysis for 3.3 years. This is the second report of Aspergillus
      thermomutatus(telemorph: Neosartorya pseudofischeri) in humans. Comprehensive
      treatment included early removal of the CAPD catheter, the use of liposomal
      amphotericin B, and the use of itraconazole.

PMID- 11956875
TI  - Gastrostomy feeding in infants and children on peritoneal dialysis.
AB  - The majority of infants and young children on peritoneal dialysis (PD) require
      enteral feeding to achieve their growth potential. We report our experience of
      gastrostomy feeding in 29 children on PD over 11 years. Fifteen children, median
      age 3.9 (0.5-13.3) years had a percutaneous gastrostomy (PEG) or Nissen
      fundoplication and gastrostomy (N and G) or open gastrostomy (OG) before starting
      PD (group1). Nine children, age 0.7 (0.5-12.4) years, had a N and G or OG (group
      2) and 5, age 5.1 (1-15.1) years, a PEG (group 3) after PD catheter
      insertion/start of PD. In group 1 (257 months gastrostomy feeding with PD), there
      were 0.6 episodes of peritonitis/patient year. Nine PEGs were replaced electively
      after 27 (19-50) months, with bleeding from an embedded flange the only
      complication. One PEG replaced by a button ruptured the track, causing Candida
      peritonitis. In group 2 (130 months G and PD), there were 1.4 episodes of
      peritonitis/patient year. Two children developed paraoesophageal hernias, which
      were successfully repaired. Four children in group 3 developed peritonitis soon
      after PEG placement. Two transferred to haemodialysis, 1 remained on PD after
      treatment of Candida peritonitis and 1 subsequently died. Only 2 of the 17
      children who have had renal transplants still need gastrostomy feeds. We
      recommend placement of a PEG or OG if an anti-reflux procedure is necessary prior
      to starting PD. Placement of a PEG while on PD is contraindicated, but an OG is a
      safe alternative procedure.

PMID- 11956876
TI  - Associations with medication adherence among ethnically different pediatric
      patients with renal transplants.
AB  - This study examined perceived medication regimen characteristics as factors in
      levels of medication adherence among 26 African American and 42 European American
      pediatric renal transplant patients. Among both groups, perceived characteristics
      of their medication regimen, including pill size, pill taste and medication
      complexity, were found to have significantly low to moderate associations with
      medication adherence. These associations were stronger and more consistent across
      medication adherence measures among the African American patients. This supports
      the need to separately examine the factors contributing to medication adherence
      among ethnically different pediatric patients. Suggestions for promoting
      medication adherence among pediatric patients with renal transplants and
      implications for future research are discussed.

PMID- 11956877
TI  - ANCA-positive glomerulonephritis and IgA nephropathy in a patient on
      propylthiouracil.
AB  - A 14-year-old girl developed acute renal failure after 3 years therapy with
      propylthiouracil (PTU) for Grave's disease. Serologic evaluation showed
      antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 and
      myeloperoxidase. Renal biopsy showed a crescentic glomerulonephritis (GN) as well
      as evidence of IgA nephropathy (IgAN). PTU was discontinued and the patient was
      treated with prednisone and cyclophosphamide. ANCA became negative and renal
      function improved, but did not normalize. A second biopsy showed evidence of IgA
      nephropathy only. Propylthiouracil use has been associated with ANCA positive
      pauci-immune glomerulonephritis, but not with IgA nephropathy. An overlap
      syndrome between IgAN and ANCA-positive GN, however, has been described. This
      patient may have had a preexisting IgAN, with acute pauci-immune GN secondary to
      PTU, or this may be the first description of an overlap syndrome of IgAN and ANCA
      vasculitis all caused by PTU therapy.

PMID- 11956878
TI  - Pneumothoraces complicating systemic lupus erythematosus with nephritis.
AB  - Pneumothorax is an infrequently reported complication of systemic lupus
      erythematosus (SLE) and carries with it a grave prognosis. We report a patient
      with SLE and nephritis who developed pneumothorax that responded to aggressive
      and prolonged therapy. Surgical management with prolonged evacuation, judicious
      immunosuppression, and aggressive diagnosis and treatment of infection can
      improve the outcome for these patients.

PMID- 11956879
TI  - Nephrocalcinosis in preterm infants: a single center experience.
AB  - The risk of nephrocalcinosis in preterm infants is considerable, but conflicting
      numbers are given for the actual incidence (10-65%). Furosemide induced
      hypercalciuria is said to be the main risk factor. We examined retrospectively
      the incidence, causes and outcome of nephrocalcinosis in preterm infants born in
      our hospital from 1988 to 1998 ( n=2190). An abnormal renal echogenicity or
      nephrocalcinosis was seen in 31 infants (29.7+/-3.3 weeks gestational age; 1307+/
      690 g birth weight). Nephrocalcinosis was diagnosed in 16, hyperechoic kidneys
      (HK) in 10 and Tamm-Horsfall kidneys in 5 infants. Main risk factors were low
      gestation age and birth weight, length of hospitalization, variations in acid
      base status, length of assistant ventilation and hypercalciuria at diagnosis. The
      incidence of nephrocalcinosis was 0.73% [1.7% for low birth weight infants
      (VLBW)]. Taking the cases of nephrocalcinosis and HK together, incidence was
      calculated to be 1.2% overall and 2.5% for VLBW infants, but increased to 7% in
      1998. The follow-up showed persisting nephrocalcinosis or hyperechoic kidneys in
      8/26 preterm infants. In conclusion, the incidence of nephrocalcinosis was lower
      in our population than is usually reported. The numbers have, however, increased
      over the past few years. From the follow-up it was obvious that long-term
      observation of preterm infants is necessary and that complications might arise in
      the long run.

PMID- 11956880
TI  - Poland syndrome associated with renal agenesis.
AB  - Poland syndrome is characterized by unilateral aplasia or hypoplasia of the
      sternocostal portion of the pectoralis major muscle and ipsilateral syndactyly.
      In some cases other associated anomalies, including renal malformations,
      dextrocardia, and vertebral abnormalities, have been reported. We report a 7
      month-old girl with Poland syndrome who also presented with ipsilateral renal
      agenesis. This report suggests that renal structural anomaly may be an integral
      part of this syndrome. We recommend renal imaging studies be performed on all
      children with Poland syndrome.

PMID- 11956881
TI  - Voiding urosonography with ultrasonography contrast medium in children.
AB  - Voiding urosonography (VUS) with ultrasonography contrast medium is a new
      modality in the detection of vesicoureteral reflux (VUR) in children. The purpose
      of this study was to evaluate the diagnostic accuracy of VUS compared with
      voiding cystourethrography (VCUG) in the detection of VUR. One hundred and
      eighteen patients, aged 3 weeks to 16 years, with 234 ureterorenal units, were
      investigated by VUS with ultrasonography contrast medium and radiographic VCUG in
      one session. The indications were predominantly urinary tract infection and
      follow-up of previously detected VUR. During the sonographic examination, the
      bladder was filled with saline solution and an ultrasonography contrast medium
      (Levovist) was administered through a catheter. Reflux was diagnosed when
      echogenic bubbles were observed in the ureter or in the renal pelvis. Afterwards,
      conventional VCUG was performed. Concordant findings were obtained in 210 of 224
      ureterorenal units (93.7%). Reflux was excluded by both methods in 174 units
      (77.7%). With the VCUG as the reference, the sensitivity of VUS was 90%, the
      specificity 94.6%, the positive predictive value 78.3%, and the negative
      predictive value 97.8%. The accuracy was 93.7%. In conclusion, VUS with
      ultrasonography contrast medium is a reliable diagnostic tool for the detection
      of VUR in children.

PMID- 11956882
TI  - Renal angiography in children with polyarteritis nodosa.
AB  - This study describes the angiographic findings in children with polyarteritis
      nodosa (PAN). Visceral angiograms of 25 children with PAN were reviewed
      retrospectively by two independent radiologists. In the PAN group, 40% of
      children had aneurysms demonstrated on selective renal angiography. Most
      aneurysms affected small and medium-sized arteries. There was agreement between
      radiologists regarding medium and large aneurysms ( K=0.81), but less so for
      smaller aneurysms. Overall, the presence of medium or large aneurysms was
      significantly associated with the presence of renal impairment and hypertension.
      Non-aneurysmal changes were detected more commonly on renal angiography than
      aneurysms in the PAN group. The most reliable non-aneurysmal signs were perfusion
      defects, the presence of collateral arteries, lack of crossing of peripheral
      renal arteries, and delayed emptying of small renal arteries. The sensitivity and
      specificity of renal angiographic diagnosis of PAN using aneurysms alone was 43%
      (SE 10%) and 69% (SE 14%) respectively. The sensitivity increased to 80%, and
      specificity fell to 50% for angiogram positivity defined as the presence of at
      least one of the most reliable non-aneurysmal signs irrespective of the presence
      of aneurysms. Aneurysms were also demonstrated on hepatic and mesenteric
      angiography, and non-aneurysmal signs were found on hepatic, mesenteric, and
      splenic angiography, although interobserver agreement for angiographic findings
      in these vascular beds was lower. It is important to consider both aneurysmal and
      non-aneurysmal angiographic signs, and to include examinations of several
      vascular beds when utilising angiography for diagnostic purposes in children with
      PAN.

PMID- 11956883
TI  - Patchy renal vasoconstriction after exercise in a child without renal
      hypouricemia.
AB  - Here, I present a case of patchy renal vasoconstriction and renal injury in a
      girl without renal hypouricemia, following exercise and ingestion of an
      analgesic. For the previous 2 years, she had suffered from re-current abdominal
      pain following exercise. Postcontrast renal computed tomographic scan showed low
      density patchy areas immediately after contrast medium injection, and then patchy
      wedge-shaped contrast enhancement 22 h later. These symptoms and signs are
      typical findings of patchy renal vasoconstriction. Although precise mechanisms
      for the development of patchy renal vasoconstriction after exercise in patients
      without renal hypouricemia remain obscure, both exercise and ingestion of an
      analgesic were active in the development of patchy renal vasoconstriction and
      renal injury in our patient.

PMID- 11956884
TI  - Asymptomatic intracardiac thrombus in steroid-sensitive nephrotic syndrome.
AB  - Arterial and venous thrombotic events can lead to severe complications in the
      nephrotic syndrome, but may remain clinically silent in a substantial proportion
      of patients. Intracardiac thrombi associated with multiorgan thrombosis have been
      described in autopsy cases of the earlier literature, but have never been
      documented in vivo. We here report an asymptomatic intracardiac thrombus in a
      child with frequently relapsing steroid-sensitive nephrotic syndrome and a
      ventricular septal defect.

PMID- 11956885
TI  - Lithium-induced nephrotic syndrome in a young pediatric patient.
AB  - Lithium-induced nephrotic syndrome is a rare complication of lithium therapy and
      is even rarer in children. Most reported cases have been secondary to minimal
      change disease, which reverses within 1-4 weeks on discontinuation of lithium
      therapy. However, focal glomerulosclerosis (FSGS) has occasionally been reported
      and is not always reversible with discontinuation of lithium. We report an 11
      year-old child with lithium-induced FSGS nephrotic syndrome who went into full
      remission after lithium was discontinued.

PMID- 11956886
TI  - Hemolytic uremic syndrome: epidemiology, pathophysiology, and therapy.

PMID- 11956887
TI  - Pulse methylprednisolone treatment of idiopathic steroid-resistant nephrotic
      syndrome.

PMID- 11956889
TI  - Additive antiproteinuric effect of ACE inhibitor and losartan in IgA nephropathy.

PMID- 11956890
TI  - Ask the expert. Does antibody induction therapy with daclizumab or basiliximab
      increase the risk of recurrence of post-transplant focal segmental
      glomerulosclerosis?

PMID- 11956894
TI  - [Neurobiological mechanisms of acupuncture analgesia].
AB  - AIM: The aim of this review is to present the findings of basic research about
      mechanism of acupuncture-induced analgesia (AA) on the basis of the relevant
      literature. The transferability of the results into practice and theory of
      traditional acupuncture are critically discussed. METHOD: Extensive literature
      research was used to identify and summarize relevant studies. RESULTS: AA has
      been proven by biochemical, immunohistochemical, molecular biological and
      neurophysiological investigations. It has been shown that short term AA is
      mediated by an activation of endogenous antinociceptive systems and descending
      inhibitory systems. Long term effects cannot be explained sufficiently by
      experimental results; however, they suggest an involvement of long term
      inhibitory synaptic modification at spinal cord neurons and clinical and
      radiological findings indicate limbic system modulation. CONCLUSION: Regarding
      the complexity of endogenous pain-inhibitory systems and the methodological
      shortcomings many questions remain unanswered. Further research activities are
      necessary in this field.

PMID- 11956895
TI  - [Investigations on the effect of acupuncture on affective and sensory components
      of pain in patients with different stages of chronic pain].
AB  - OBJECTIVES: The aim of the study was to investigate the effects of acupuncture on
      the affective and sensory experience of pain in chronic pain patients.
      Furthermore, the study tried to estimate the therapeutical benefit of acupuncture
      in relation to the stage of chronic pain according to the Mainz pain staging
      system for chronic pain (MPSS). METHODS: Patients with chronic pain syndromes who
      received acupuncture treatment answered a standardized pain questionnaire before
      and after treatment. The questionnaire included the visual-analogue-scale for the
      intensity of pain, the pain perception scale for the assessment of affective and
      sensory components of pain perception, and addressed the patients to the three
      stages of chronic pain (MPSS). RESULTS: From April 1997 to October 1999, patients
      (n = 165) suffering from chronic headache and facial pain syndromes (23%), spine
      associated pain syndromes (48%) or other pain conditions (29%) were subsequently
      included. Treatment with acupuncture showed a more pronounced reduction of the
      affective assessment than of the sensory assessment of pain. These effects were
      particularly pronounced in patients assigned to stage 3 of chronic pain (MPSS).
      CONCLUSIONS: Acupuncture in patients with high-stage chronic pain syndromes
      preferentially influences the affective dimension of pain perception. For the
      estimation of the overall clinical outcome of acupuncture treatment, a
      differentiation between affective and sensory components of pain is recommended.

PMID- 11956896
TI  - [Electric stimulation acupuncture in peripheral neuropathic pain syndromes.
      Clinical pilot study on analgesic effectiveness].
AB  - AIM: The aim of this pilot study was to investigate the potential value of
      acupuncture in the treatment of peripheral neuropathic pain. Explorative analysis
      should provide data for further randomised controlled trials. METHOD: In an
      uncontrolled clinical trial electroacupuncture was given to 17 patients with
      chronic neuropathic pain of peripheral origin which was resistant to preceding
      pain therapy. Patients were treated twice weekly for 4 weeks. Assessment of
      outcome measurements comprised: Intensity of continuous pain (visual analogue
      scale, VAS), intensity of pain attacks (VAS), duration of pain attacks, number of
      pain attacks and changes in mood (VAS). All measures were evaluated by diary (1
      week before treatment to 2 weeks after treatment and 1 week at follow up three
      months after treatment). Changes of global complaints and patients' beliefs in
      treatment (credibility assessment) were also assessed. RESULTS: At re-evaluation
      two weeks after treatment, mean continuous pain was reduced by 32.9% and
      intensity of pain attacks was reduced by 59%. Mean number of daily pain attacks
      decreased from 4.2 (SD +/- 4.6, 0.14-13.3) before treatment to 2.2 (SD +/- 3.8, 0
      7.5) two weeks after treatment. Duration of pain attacks and mood showed no
      substantial changes. Three months after treatment, continuous pain was reduced by
      15.9% and intensity of pain attacks was reduced by 44% compared to baseline. No
      serious adverse events were observed CONCLUSIONS: On the basis of this small
      pilot study, trial treatment by electroacupuncture seems to be justified in these
      patients given a lack of success of standard treatments. The apparent beneficial
      analgesic effects of electroacupuncture appear to warrant further investigation.

PMID- 11956897
TI  - [Acupuncture in the treatment of locomotive disorders - status of research and
      situation regarding clinical application].
AB  - Acupuncture has been used for over 2000 years for a wide variety of complaints
      with minimal side effects. Based on the experience in Chinese medicine and the
      anticipated positive effects, acupuncture has been widely accepted in Western
      medicine as well. Some clinical evidence supports the efficacy of acupuncture
      treatment, but randomized controlled trials have been conducted for only a few of
      all possible locomotive disorder indications, and the results have been
      equivocal. Other indications have not yet been systematically studied, and
      application is based on clinical experience and consensus among practitioners.
      One of the outcomes on which consensus appears to exist is that 10-20 sessions
      are generally necessary, and that initial improvement can be expected to occur by
      the 10th treatment. Rigorous trials should be conducted to improve clinical
      validity and provide scientific proof of the efficacy of acupuncture. Clinical
      trials like the German Acupuncture Trials (gerac), funded by the German health
      insurance companies, have been launched with the aim of furthering knowledge in
      this area.

PMID- 11956898
TI  - [Acupuncture for back pain: meta-analysis of randomised controlled trials and an
      update with data from the most recent studies].
AB  - BACKGROUND: Acupuncture is commonly used to treat back pain. A meta-analysis of
      clinical trials of acupuncture for this condition came to a positive conclusion
      whilst a qualitative review was negative. AIM: To compare our meta-analysis of
      trials of acupuncture for the treatment of back pain with a qualitative review
      and the most recent studies on the subject. METHODS: A systematic literature
      search was conducted to retrieve all randomised controlled trials of any form of
      acupuncture for any type of back pain in humans. The adequacy of the acupuncture
      was assessed by consulting six experienced acupuncturists. The main outcome
      measure for the meta-analysis was numbers of subjects who where improved at the
      end of treatment. These data are discussed in relation to the qualitative review
      and the most recent studies. RESULTS: Twelve studies were included of which nine
      presented data suitable for meta-analysis. The odds ratio of improvement with
      acupuncture compared with control intervention was 2.30 (95% confidence interval
      1.28 to 4.13). For sham-controlled, evaluator-blinded studies, the odds ratio was
      1.37 (95% confidence interval, 0.84-2.25). The results from the majority of the
      most recent studies also support the effectiveness of acupuncture in the
      treatment of back pain. CONCLUSIONS: Collectively, these data imply that
      acupuncture is superior to various control interventions, although there is
      insufficient evidence to state whether it is superior to placebo.

PMID- 11956899
TI  - [Pain control in German pediatric oncology. An inventory].
AB  - As part of a nationwide quality improvement programme, our aim is the assessment
      of the quality of pain control in German paediatric oncology to tailor the
      intervention to specific needs. Here we report on the results of a questionnaire
      based nationwide survey which addressed the head of the department, one
      supervising physician, one ward physician, one nurse, and one psychologist/social
      worker in each of the 76 german paediatric oncology departments. 210/380 health
      care professionals of 60/76 departments responded to the survey. According to 17%
      of the physicians (41% of the nurses, p = 0.004) there still exists '(very)
      often' pain despite pain therapy. Procedures are seen as the main causes of pain.
      According to 58% of the heads of the department and supervising physician (35% of
      the nurses and ward physicians, p = 0.005), faces scales are regularly used to
      score pain intensity. In 80% of the departments a written therapy protocol
      addressing procedure-related, or postoperative pain is lacking. When larger and
      smaller departments are compared, in former ones the significantly preferred
      routes for opioid administration are i. v., or oral for slow release preparations
      (p = 0.01). The i. m. route is exclusively used in smaller departments. In the
      treatment of neuropathic pain, only 5% of the physicians regard morphine, but 25%
      of them regard antidepressants and antiepileptics as ineffective. Only 72% of the
      physicians (39% of the nurses, p = 0.001) are convinced that during opioid-based
      pain therapy addiction 'seldom/never' developes. Nurses are less satisfied with
      pain therapy than are physicians, and they feel more frequently that pain therapy
      '(very) often' starts too late (p <0.005). The questionnaire revealed obvious
      deficits in both physicians' and nurses' knowledge regarding pain therapy.
      Deficits were also addressed by the health care professionals themselves.

PMID- 11956900
TI  - Indications for curative resection of advanced gallbladder cancer with
      hepatoduodenal ligament invasion.
AB  - PURPOSE: Hepatoduodenal ligament invasion (HLI) is an inhibiting factor for the
      curative resection of advanced gallbladder cancer. The aim of this study was to
      clarify the indications for surgical resection in patients with advanced
      gallbladder cancer with and without HLI by analyzing outcomes. METHODS: The
      subjects were 58 patients with advanced gallbladder cancer who underwent
      aggressive resection, and 20 nonresected patients diagnosed as haring HLI. The
      presence of stromal cancerous infiltration at six sites in the hepatoduodenal
      ligament was investigated. The extent of cancer spread was classified into two
      grades by the number of sites where cancer cells detected: low grade, one or two
      invasion sites; high grade, three or more sites. RESULTS: Pancreatoduodenectomy,
      vascular reconstruction, and extensive hepatectomy were frequently performed in
      the patients with HLI. The cumulative 5-year-survival rate of the HLI patients
      was 10.9%, significantly worse than that of the resected patients without HLI
      (46.6%; P < 0.01). Patients with paraaortic lymph node metastasis died within 1
      year. The cumulative 5-year-survival rate after curative resection was 38.1%,
      significantly better than that after noncurative resection (0%; P < 0.05). The
      survival was significantly worse in patients with high-grade invasion than in
      these with low-grade invasion (P < 0.05), being equivalent to that in the
      nonresection patients. Of four factors, operative curability, hepatic lobectomy,
      HLI grade, and paraaortic lymph node metastasis, the HLI grade and hepatic
      lobectomy were considered to be significant prognostic factors by Cox's
      multivariate analysis (backward stepwise method). CONCLUSIONS: Aggressive
      surgical resection for curative purposes should be limited to patients with low
      grade HLI and metastasis-negative paraaortic lymph nodes.

PMID- 11956901
TI  - Five-year survivors after aggressive surgery for stage IV gallbladder cancer.
AB  - PURPOSE: To describe 5-year survivors after radical surgery for stage IV
      gallbladder cancer and to determine the characteristics leading to potential long
      term survival. METHODS: Of 59 patients undergoing radical resection for stage IV
      disease between 1979 and 1994, 6 patients who have survived for more than 5 years
      were followed up. RESULTS: Three patients had developed obstructive jaundice due
      to involvement of the hepatic hilum, but the other three had not. The jaundiced
      patients had remarkable tumor spread over the bile duct and right hepatic artery
      within the hepatoduodenal ligament. However, the proper and left hepatic arteries
      and the portal trunk and its left branch were free from tumor involvement. The
      nonjaundiced patients had N1 or N2 lymph node metastasis. However, none underwent
      bile duct resection or pancreatoduodenectomy to establish radical
      lymphadenectomy. CONCLUSIONS: Selected patients with stage IV gallbladder cancer
      may be candidates for 5-year survival when the primary tumor is fairly localized
      even if it forms a large mass and involves neighboring organs including the
      hepatic duct, lymph node metastasis is limited to N1 and N2 except for the celiac
      and superior mesenteric nodes and is less infiltrative, and distant metastasis
      including that in the paraaortic area is absent.

PMID- 11956902
TI  - Irradiation therapy for gallbladder carcinoma: recent advances.
AB  - PURPOSE: Gallbladder carcinomas were usually considered to be radioresistant. So
      far, the role of radiotherapy has not been adequately evaluated. The aim of this
      report is to assess the value of radiotherapy in carcinoma of the gallbladder.
      METHODS: We reviewed publications concerning the role of radiation therapy in
      gallbladder carcinoma from 1974 to 2000. External radiation therapy,
      intraoperative radiation therapy, and brachytherapy were evaluated in two
      different groups: one group of patients underwent surgery, with apparently
      complete resection of the tumor; and another group underwent palliative
      treatment. RESULTS: Local control of the tumor and reduction of tumor size were
      reported in several publications. Collected data suggested a slight improvement
      in survival after adjuvant or palliative radiotherapy. The best benefit was
      obtained in tumors resected with only microscopic residual tissue. If possible an
      intraoperative "boost" (15 Gy) is recommended on the gross lesion, residual
      lesion, or tumor bed. Additional postoperative external radiotherapy (45-50 Gy)
      must be delivered. CONCLUSION: Radiotherapy appears to be a safe procedure that
      slightly improves the survival time of patients treated for gallbladder
      carcinoma. Further trials are needed to assess the role of combined radiotherapy
      and chemotherapy.

PMID- 11956903
TI  - Open versus laparoscopic cholecystectomy for gallbladder carcinoma.
AB  - Laparoscopic surgery has replaced conventional open cholecystectomy for benign
      gallbladder disease. A major concern is how to handle gallbladder cancer in the
      laparoscopic era, since there are numerous case reports of port site metastases
      from gallbladder cancer after laparoscopic cholecystectomy. There are also many
      experimental studies favoring the opinion that the laparoscopic technique implies
      a higher risk of spreading malignant disease. This opinion has gained wide
      acceptance despite little previous clinical effort to determine the risk of tumor
      dissemination and the lack of comparisons between open and laparoscopic surgery.
      This report is a short summary of our own studies and present knowledge with
      special respect to the clinical aspects of the development and incidence of
      abdominal wall metastases. Among 270 patients with verified gallbladder carcinoma
      in whom 210 had open surgery and 60 a laparoscopic cholecystectomy, 12 patients
      (6.5%) in the open cholecystectomy group and 9 (15%) in the laparoscopic group
      developed incisional metastases. Although the sparse clinical documentation does
      not unavoidably mean that laparoscopic cholecystectomy has an increased risk of
      disseminating tumor cells, we recommend open surgery in cases of known or
      suspected gallbladder carcinoma.

PMID- 11956904
TI  - Present status of the diagnosis and treatment of gallbladder carcinoma.
AB  - Because early carcinoma of the gallbladder causes no specific signs or symptoms,
      most patients with this disease are diagnosed with advanced-stage tumors. High
      resolution ultrasonography and a low index of suspicion for polypoid masses or
      asymmetric gallbladder thickening represent the best method of early detection.
      Despite regular preoperative gallbladder imaging, many cancers are only detected
      intraoperatively or incidentally on pathologic examination. All known or
      suspected gallbladder cancers should be definitively treated with a laparotomy,
      not laparoscopic surgery. For early gallbladder cancers (Tis and T1 cancers),
      simple cholecystectomy is adequate therapy. More advanced-stage carcinomas
      without distant metastases should routinely be managed with a radical
      cholecystectomy, which includes partial hepatectomy and regional lymphadenectomy.
      Any adherent organs should be resected en bloc with the cancer.
      Pancreatoduodenectomy has been performed in several Japanese centers, but is
      rarely performed in the West for locally advanced gallbladder cancers. Most
      patients who undergo curative resection will develop recurrent disease, but there
      is currently no proven effective adjuvant therapy.

PMID- 11956905
TI  - Port site recurrences after laparoscopic cholecystectomy.
AB  - Port site metastasis is a well-documented event after laparoscopic procedures in
      cancer patients. We summarize current epidemiological knowledge about the risk of
      this complication after laparoscopic/conventional cholecystectomy in patients
      with unexpected gallbladder cancer as well as other intraabdominal malignancies.
      We found 174 cases of port site metastasis after laparoscopic cholecystectomy and
      12 recurrences in the surgical scar after converted or open cholecystectomy. A
      review of all case reports and its comparison with four international surveys
      show a 14% incidence of port site metastases 7 months after laparoscopic
      cholecystectomy for cancer. Similar numbers are available for open
      cholecystectomy. Our data suggest that abdominal wall metastases of gallbladder
      cancer are not a specific complication of laparoscopy. The long-term prognosis of
      patients with unknown gallbladder cancer however seems to be worsened by
      laparoscopy. The registry of the German Society of Surgery, which prospectively
      compares follow-up and prognosis of all cases of cholecystectomy, laparoscopic as
      well as open, in patients with incidental gallbladder cancer will definitively
      clarify whether laparoscopy affects the prognosis of patients with unsuspected
      gallbladder cancer.

PMID- 11956906
TI  - Trends in treatment for pancreatic cancer.
AB  - Although surgical resection is considered to be the only approach that offers a
      possibility of cure to patients with pancreatic cancer, the prognosis of the
      disease has not been improved markedly by any surgical procedures in the past 20
      years. Large-scale randomized prospective clinical trials are being conducted in
      the United States and Italy, comparing standard lymph node dissection with
      extended lymph node dissection. Although preoperative chemoradiation has various
      advantages in the treatment of pancreatic cancer, it does not contribute to its
      downstaging and eventual cure. The combination of leucovorin, 5-fluorouracil (5
      FU), and extracorporeal irradiation, however, has been proven to improve the
      patient's quality of life (QOL). Palliative surgery still requires further
      research in areas such as the examination of morbidity rates and the duration of
      bypass effects, now that laparoscopic and endoscopic surgery have both been well
      developed. Recent biological research has revealed the mechanisms of the
      carcinogenesis and the progression of pancreatic cancer, and, against this
      background, we assume that more effective trials will be conducted soon.
      Immunotherapy with dendritic cells, as well as gene therapy with mutant
      adenovirus, has already been employed clinically. Pancreatic cancer therapy is
      now facing new prospects.

PMID- 11956907
TI  - High dorsal drainage routes of Spiegel's lobe.
AB  - BACKGROUND/PURPOSE: The venous drainage from Spiegel's lobe to the terminal
      portion of the hepatic veins has been described in the literature, but its
      morphology remains unclear. METHODS: We examined 42 dissected liver specimens and
      38 cast specimens. RESULTS: In 8 of the 42 dissected liver specimens and 5 of the
      38 cast specimens we found atypical but thick (over 3 mm) caudate veins that
      drained Spiegel's lobe and emptied into the terminal portion (along the most
      proximal 5-mm course) of the middle hepatic vein (MHV) or the inferior vena cava
      (IVC) near the MHV terminal (less than 10 mm from the MHV). We termed these the
      superior caudate vein. This vein ran upward between the caudate portal branches
      of the left and hilar bifurcation origins or through the territory of the left
      origin. The superior caudate vein, consistently coexisted with the typical
      vein(s). We also found several analogues of the superior caudate vein, such as
      the cranially shifted opening of the typical caudate vein and relatively thick
      proximal tributaries of the MHV from Spiegel's lobe. CONCLUSIONS: Although the
      superior caudate vein, if present, seemed to have a large role in the venous
      drainage of the lobe, its incidence seemed to be too low for clinical relevance.

PMID- 11956908
TI  - Analysis of postrevascularization syndrome after orthotopic liver
      transplantation: the experience of an Australian liver transplantation center.
AB  - BACKGROUND/PURPOSE: We investigated the causes and examined patient outcomes
      following the postrevascularization syndrome (PRS) during orthotopic liver
      transplantation (OLTx). METHODS: PRS was defined as a fall in the mean arterial
      pressure at 5 min after revascularization to less than 70% of the baseline and
      lasting for 5 min. Data from 100 adult patients who underwent OLTx between
      January 1998 and September 2000 were analyzed. Analyzed data included donor and
      recipient demographic data, recipient operative and postoperative courses, and
      recipient outcome. RESULTS: Twenty-nine patients (29%) exhibited PRS during OLTx
      (PRS group). There was a higher incidence of older donors (>50 years) in the PRS
      group (48% vs 23%; P < 0.05). Postrevascularization hyperkalemia and metabolic
      acidosis were observed in both the PRS and non-PRS groups. Transaminase and
      lactate levels after revascularization were significantly higher in the PRS group
      ( P < 0.05). Alkaline phosphatase and gamma-glutamyl transpeptidase levels on day
      7 tended to be higher in the PRS group; although the difference was not
      significant (p > or = 0.05). Serum creatinine was significantly elevated on day 7
      in the PRS group ( P < 0.01). CONCLUSIONS: Our results indicate that PRS
      following OLTx tended to be more common in liver allografts from older donors and
      was associated with posttransplantation liver and renal dysfunction.

PMID- 11956909
TI  - Cytoreductive surgery combined with intraoperative chemo-hyperthermia and
      postoperative radiotherapy in the management of advanced pancreatic
      adenocarcinoma: feasibility aspects and efficacy.
AB  - BACKGROUND/PURPOSE: The aim of our study was to evaluate the feasibility and the
      efficacy of cytoreductive surgery (CS) with intraoperative chemo-hyperthermia in
      the management of advanced stage IVA (T4N0M0) pancreatic cancer. METHODS: From
      August 1995 through March 1996, seven patients with unresectable adenocarcinoma
      of the pancreas underwent CS, with preoperative chemotherapy (5-fluorouracil [FU]
      for 96 h), plus 45-Gy external beam postoperative irradiation with a 6-MeV linear
      accelerator (1.8 Gy per fraction, 5 days per week). A single session of
      intraoperative hyperthermia was performed with a waveguide-type applicator
      operating at 433 MHz, and temperature was measured by inserting a flexiguide
      needle catheter carrying a thermometry probe with three measuring points into the
      tumor. The tumor region was heated to 43 degrees C-45 degrees C for up to 60 min,
      while 5-FU 500 mg was injected simultaneously through the gastroduodenal artery
      into the splenic artery (intraoperative regional chemotherapy). RESULTS:
      Postoperative recovery was uneventful for all patients. After the combined
      treatment, there was a significant decrease in the values of both serum
      carcinoembryonic antigen (CEA; P = 0.017, Wilcoxon test) and carbohydrate antigen
      (CA)19-9 ( P = 0.016; Wilcoxon test), from 7.6 +/- 1.5 ng/ml CEA and 869.6 +/-
      126.9 U/ml CA to 3.5 +/- 0.8 ng/ml CEA and 104.7 +/- 35.4 U/ml CA19-9. Moreover,
      there was a significant improvement ( P = 0.016; Wilcoxon test) in Eastern
      Cooperative Oncology Group performance status, pain score, and body mass index.
      The median overall survival was 18.5 (SE, 1.8) months. CONCLUSIONS: Our
      preliminary clinical results suggest the tolerability and the considerable
      potential advantage of using cytoreductive resection with preoperative
      chemotherapy, intraoperative chemo-hyperthermia, and external beam postoperative
      radiotherapy for the management of advanced adenocarcinoma of the pancreas.

PMID- 11956910
TI  - Chylous ascites after liver transplantation with mesentero-portal jump graft.
AB  - Chylous effusions and lymphatic leaks occur after trauma, malignant disease,
      primary lymphatic disorders, and parasitosis, and rarely after abdominal surgery.
      Chylous ascites after orthotopic liver transplantation is a rare complication. We
      report a case of chylous ascites occurring after hepatic transplantation with a
      mesentero-portal venous jump graft, successfully treated with conservative
      management.

PMID- 11956911
TI  - Reversal of portal flow after acute rejection in living-donor liver
      transplantation.
AB  - Portal hepatofugal flow is rare after liver transplantation. We experienced a
      case in which hepatofugal portal flow was observed in acute rejection. A 6-year
      old boy with glycogen storage disease type Ia underwent living-donor liver
      transplantation. On postoperative day 7, portal venous peak velocity was markedly
      decreased without portal thrombosis and obstruction of the hepatic vein, and
      hepatic arterial peak velocity increased reciprocally. Based on a diagnosis of
      acute rejection, made on postoperative day 8, we initiated steroid pulse therapy.
      Despite the employment of this therapy, continuous hepatofugal portal flow was
      observed in the entire liver on postoperative day 8. On day 12, as the liver
      disorder progressed, the Doppler waveform in the portal vein changed from
      continuous to pulsatile hepatofugal flow. The patient died of liver failure on
      day 14. The histological findings of a biopsy specimen on day 9 showed
      centrilobular necrosis, while total hepatocellular necrosis was seen at autopsy.
      Hepatofugal flow after liver transplantation is considered to be an ominous sign
      caused by several factors, and its appearance indicates a fatal condition.

PMID- 11956913
TI  - Weight distribution in the sitting position in patients with paralytic scoliosis:
      pre- and postoperative evaluation.
AB  - Patients with paralytic scoliosis spend most of their time in the sitting
      position. The spinal deformity, pelvic obliquity and uneven weight distribution
      on the seating surface necessitates frequent seating adaptations in the
      wheelchair. In this prospective study, 45 wheelchair-bound patients were
      evaluated preoperatively and 43 postoperatively. The pre- and postoperative
      evaluation was done by an independent observer. Surgical correction was performed
      between 1993 and 1996. Assessments included sitting balance on a box; number of
      seating supports in the wheelchair; weight distribution on the seating surface,
      measured with a computerized EMED system; Cobb angle; hip dislocation;
      mediolateral translation of T1 and of the apex vertebra with reference to a
      perpendicular line drawn upwards from the spinal process of S1; and pelvic
      obliquity from a line drawn between the most proximal points in the iliac crests.
      X-rays for the measurement of Cobb angle and pelvic obliquity were performed in
      sitting position. Reference values for normal weight distribution on the seating
      surface were obtained for 27 normal subjects and revealed a mean value of 59% of
      weight supported on one side. A stepwise regression analysis on the preoperative
      results showed that pelvic obliquity and thoracolumbar/lumbar spinal imbalance
      explained weight distribution on the seating surface (R(2)=0.45). There were
      significant improvements in all variables except in sitting balance and imbalance
      of T1, 1 year postoperatively. When dividing the material into two subgroups, the
      results showed no significant difference in any of the assessed parameters of the
      scoliosis, pelvic obliquity, or sitting position between individuals with even
      (50-59% on one side) and those with uneven (60-100% on one side) weight
      distribution postoperatively. The results of the assessment showed a significant
      improvement after surgical correction, but the majority still had pelvic
      obliquity and uneven weight distribution in a sitting position. The weight
      distribution on the seating surface preoperatively was explained by
      thoracolumbar/lumbar spinal imbalance and pelvic obliquity, with R(2)= 0.45.
      There were no significant differences in any variables in comparisons between
      individuals with even weight distribution and those with uneven weight
      distribution. For the group with even weight distribution, however, the mean
      pelvic obliquity was 6 degrees and in the group with uneven weight distribution
      the mean pelvic obliquity was 12 degrees. Attention to seating surface and
      adjustment of seating position is needed for patients with paralytic scoliosis.

PMID- 11956914
TI  - Scoliosis correction with shape-memory metal: results of an experimental study.
AB  - The biocompatibility and functionality of a new scoliosis correction device,
      based on the properties of the shape-memory metal nickel-titanium alloy, were
      studied. With this device, the shape recovery forces of a shape-memory metal rod
      are used to achieve a gradual three-dimensional scoliosis correction. In the
      experimental study the action of the new device was inverted: the device was used
      to induce a scoliotic curve instead of correcting one. Surgical procedures were
      performed in six pigs. An originally curved squared rod, in the cold condition,
      was straightened and fixed to the spine with pedicle screws. Peroperatively, the
      memory effect of the rod was activated by heating the rod to 50 degrees C by a
      low-voltage, high-frequency current. After 3 and after 6 months the animals were
      sacrificed. The first radiographs, obtained immediately after surgery, showed in
      all animals an induced curve of about 40 degrees Cobb angle - the original curve
      of the rod. This curve remained constant during the follow-up. The postoperative
      serum nickel measurements were around the detection limit, and were not
      significantly higher compared to the preoperative nickel concentration.
      Macroscopic inspection after 3 and 6 months showed that the device was almost
      overgrown with newly formed bone. Corrosion and fretting processes were not
      observed. Histologic examination of the sections of the surrounding tissues and
      sections of the lung, liver, spleen and kidney showed no evidence of a foreign
      body response. In view of the initiation of the scoliotic deformation, it is
      expected that the shape-memory metal based scoliosis correction device also has
      the capacity to correct a scoliotic curve. Moreover, it is expected that the new
      device will show good biocompatibility in clinical application. Extensive fatigue
      testing of the whole system should be performed before clinical trials are
      initiated.

PMID- 11956915
TI  - Three-stage surgery in the management of severe rigid angular kyphosis.
AB  - There are conflicting data regarding the management of rigid kyphosis. None of
      the currently known techniques can completely correct severe kyphosis without
      resulting in residual deformity. Seven patients with local kyphosis exceeding 60
      degrees were operated on to achieve complete correction of the deformity. The
      surgery consisted of total spondylectomy of the deformed vertebra and
      simultaneous application of compression-distraction forces to this area. The
      operation included three stages: The initial stage includes resection of
      posterior spinal elements and temporary fixation. In the second stage, an
      anterior corpectomy is performed to conclude the resection, and simultaneous
      antero-posterior correction is obtained. The final stage includes another
      posterior procedure to achieve a precise correction and to correct any
      compensatory curves. All patients were operated on using this technique in a
      single session. The mean preoperative and postoperative kyphosis angles were 76.1
      degrees (range, 65 degrees -92 degrees) and 6 degrees (range, 0 degrees -13
      degrees), respectively. Complete bony fusion was achieved after a mean follow-up
      period of 38 months (range, 26-52 months) without any neurological sequelae or
      significant loss of correction.

PMID- 11956916
TI  - Measurement of spinal canal diameters in young subjects with lumbosacral
      transitional vertebra.
AB  - Despite the high prevalence of lumbosacral transitional vertebra (LSTV), little
      is known about the biomechanics of this condition. In addition, as previous
      studies have focused solely on symptomatic and elderly LSTV patients, the
      relationship between LSTV and congenital or developmental spinal stenosis remains
      uncertain. In the present study, the spinal canal diameters were measured in
      young subjects in whom degenerative changes have not yet become significant.
      Seventeen young adults with LSTV and 24 normal controls were included in this
      study. The spinal canal sagittal diameter, interpedicular distance, interfacet
      distance and lateral recess diameter were measured using CT scans. There was no
      significant difference in the measured values between the two groups. In
      conclusion, the results indicate that there is no relationship between LSTV and a
      congenitally narrower canal.

PMID- 11956917
TI  - The sagittal anatomy of the sacrum among young adults, infants, and
      spondylolisthesis patients.
AB  - The anatomic pelvic parameter "incidence" - the angle between the line
      perpendicular to the middle of the sacral plate and the line joining the middle
      of the sacral plate to the center of the bicoxo-femoral axis - has been shown to
      be strongly correlated with the sacral slope and lumbar lordosis, and ensures the
      individual an economical standing position. It is important for determining the
      sagittal curve of the spine. The angle of incidence has also been shown to depend
      partly on the sagittal anatomy of sacrum, which is established in childhood while
      learning to stand and walk. The purpose of this study was (1) to define the
      relationship between the sacrum and the angle of incidence, and (2) to compare
      these parameters in three populations: young adults, infants before walking, and
      patients with spondylolisthesis. Forty-four normal young adults, 32 infants not
      yet walking and 39 patients with spondylolisthesis due to isthmic spondylolysis
      underwent a sagittal full-spine radiography. A graphic table and the software for
      bidimensional study of the sacrum developed by J. Hecquet were used to determine
      various anatomic and positional parameters. Comparison tests of means, and
      multiple and partial correlation tests were used. A study of the reliability of
      the measurements using factorial plan methods was performed. The sagittal
      anatomic parameters of the sacrum were found to have a close relationship with
      the pelvic parameter of incidence angle, and therefore with the sagittal balance
      of the spine. The anatomy of the sacrum in spondylolisthesis patients is
      particular in that some features are much like those of young infants, but it is
      more curved and the incidence angle is significantly larger. There is a close
      relationship between angle of incidence and the slip of spondylolisthesis. All
      the parameters of young infants are significantly smaller than those of adults.
      It can be concluded that the sagittal anatomy of the sacrum plays a key role in
      spinal sagittal balance. The sacral bone is an integral a part of the pelvis and
      constitutes the undistorted part of the spinal curves. Organization of sagittal
      curves during growth can be followed up by looking at the sacrum. The sacrum in
      the spondylolisthesis group differs from the normal, and the greater angle of
      incidence and sacral slope in this group could predispose to vertebral slip.

PMID- 11956918
TI  - Italian version of the Roland Disability Questionnaire, specific for low back
      pain: cross-cultural adaptation and validation.
AB  - Over the last 10 years, patient-oriented evaluations using questionnaires have
      become an important aspect of clinical spinal outcome studies. Any questionnaire
      must be translated and culturally adapted in order to be used with different
      language groups, and the translated version must then be evaluated for
      reliability and validity, which are fundamental attributes of any measurement
      tool. The Roland Disability Questionnaire, a low back pain disease-specific tool,
      was submitted to translation into Italian and to cross-cultural adaptation
      following the Guillemin criteria. It was then validated on 70 patients (37 male
      and 33 female; mean age 58, range: 28-67) suffering from low back pain as
      assessed by clinical examination, imaging and also electromyography in cases of
      suspected neurological impairment. The test-retest reliability, assessed with
      intraclass correlation, was 0.92 and the internal consistency reached a
      Cronbach's alpha of 0.82. The Italian version of the Roland Disability
      Questionnaire satisfied the validation criteria, showing characteristics of
      reliability and validity similar to previously published versions translated and
      adapted for other countries.

PMID- 11956919
TI  - Lumbar lateral interbody cage with plate augmentation: in vitro biomechanical
      analysis.
AB  - Many studies have concluded that stand alone cages provide limited stabilization
      to the spine, and this primary stabilization decreases postoperatively due to
      various factors. A supplemental fixation may, therefore, be needed to improve the
      stability. Extensive biomechanical analysis was performed in the present study to
      further evaluate the stabilization achieved by a laterally inserted cage and the
      role of an anterior lateral supplemental fixation. Eight human cadaver functional
      spinal units were subjected sequentially to four different test conditions: (1)
      intact, (2) instrumented laterally with a long cylindrical threaded cage, (3) the
      same cage supplemented with a lateral fixation plate, the plate being firmly
      connected to the cage, and (4) removal of the connection between the plate and
      the cage. Pure moments were applied to each specimen in a quasi static manner,
      ranging from -7 Nm to 7 Nm in flexion/extension, lateral bending and axial
      rotation. Three-dimensional segmental motions were simultaneously recorded under
      each loading condition. Statistical analysis was carried out on the motion
      parameters, including the range of motion (ROM) and the neutral zone (NZ). Inter
      group comparisons were made using the Friedman test and the Wilcoxon test. The
      results showed that the stand alone lateral cage provided stabilization by
      increasing segmental stiffness above that of the intact spine. The stiffness
      increase ratios were: 1.6 in flexion/extension ( P=0.07), 1.3 in lateral bending
      ( P=0.4) and 1.0 in axial rotation ( P=0.67). A supplemental plate provided
      significant reinforcement of the stabilization. The stiffness increase ratios
      relative to the intact spine were: 3.1 in flexion/extension ( P=0.012), 5.0 in
      lateral bending ( P=0.012) and 2.3 in axial rotation ( P=0.012). After removal of
      the connection between the cage and the plate, the stiffness ratios were: 2.7 in
      flexion/extension ( P=0.027), 4.6 in lateral bending ( P=0.027) and 2.1 in axial
      rotation ( P=0.027). Globally, the cage alone increased the segmental stiffness
      above that of the intact spine by a factor of 1.1 ( P=0.39), with the
      supplemental plate, segmental stiffness increased by a factor of 3.1 ( P<0.01),
      and the unconnected cage/plate increased stiffness by a factor of 3.0 ( P=0.02).
      Supplementation of the lateral cage with an anterolateral plate was thus shown to
      provide significant additional stabilization in all directions, which may
      potentially compensate for the postoperative decrease in segmental stability.

PMID- 11956920
TI  - The use of a quadruped as an in vivo model for the study of the spine -
      biomechanical considerations.
AB  - Animal models in spine research are often criticized for being irrelevant to the
      human situation due to the horizontal position of the spine. Whether this is
      justified from a biomechanical point of view can be questioned. The purpose of
      the study reported here was to provide arguments that a quadruped can be a
      valuable in vivo model for the study of the spine in spite of its horizontal
      position. Relevant literature is reviewed, and biomechanical analyses were made
      of the standing and walking quadruped. Further, the vertebral trabecular bone
      architecture was quantitatively analysed by computer and interpreted in the light
      of Wolff's law. Due to the fact that spinal segments cannot withstand substantial
      bending moments, additional tensile forces from muscles and ligaments are
      necessary to control the posture of a quadruped spine. As a consequence, the
      spine is mainly loaded by axial compression. The trabeculae in a goat's vertebral
      body were found to course horizontally between its anterior and posterior
      endplates, implying that the main load within the vertebral body was indeed an
      axial compression force. The density of the vertebrae of quadrupeds is higher
      than that of human vertebrae, suggesting that the quadruped has to sustain higher
      axial compression stresses. The quadruped spine is mainly loaded along its long
      axis, just like the human spine. The quadruped can thus be a valuable animal
      model for spine research. An important point of difference is the higher axial
      compression stress in quadrupeds, which leads to higher bone densities in the
      vertebrae. This puts some limitations on the transferability of the results of
      animal experiments to the human situation.

PMID- 11956921
TI  - Cytokines and growth factors in the protruded intervertebral disc of the lumbar
      spine.
AB  - Nerve root irritation induced by factors produced by the intervertebral disc may
      play a crucial role in the pathophysiology of sciatic pain production. In this
      study we used immunohistochemistry to investigate the presence of transforming
      growth factor-beta1 (TGF-beta1), insulin-like growth factor-1 (IGF-1),
      interleukin-6 (IL-6), IL-6-receptor (IL-6R) and fibronectin in lumbar disc
      bioptic specimens from 30 patients with disc herniation (protrusion type).
      Chondrocytes of herniated discs stained positive for TGF-beta1, IGF-1, IL-6 and
      fibronectin. We demonstrated for the first time the presence of IL-6-R in the
      chondrocytes of herniated tissue. Specimens from autoptic healthy tissue were
      used as controls. In these sections no immunoreaction for TGF-beta1, IL-6, or IL
      6R was found, while they expressed IGF-1 and fibronectin, but in lower quantities
      than herniated discs. These results demonstrated the production of factors such
      as TGF-beta1, IGF-1, IL-6, IL-6R and fibronectin at the site of lumbar disc
      herniation.

PMID- 11956922
TI  - Quantitative three-dimensional anatomy of lumbar vertebrae in Singaporean Asians.
AB  - This paper details the quantitative three-dimensional anatomy of lumbar vertebrae
      L1-L5 from Asian (Singaporean) subjects based on 60 lumbar vertebrae from 12
      cadavers. The purpose of the study was to measure the dimensions of the various
      parameters of the lumbar vertebrae and thereafter to compare the data with a
      study performed on Caucasian specimens. Measurements were taken with the aid of a
      three-dimensional digitiser. The means and standard errors for linear, angular
      and area dimensions of the vertebral body, spinal canal, pedicle, and spinous and
      transverse processes were obtained for each lumbar vertebra. From this
      comparison, it was found that the dimensions of the vertebral body of the Asian
      subjects are slightly larger, with a maximum average difference of 8% for the
      posterior vertebral body height. The dimensions of the spinal canal, pedicle, and
      spinous and transverse processes of Asian subjects are smaller. The greatest
      difference can be found in the spinal canal area and pedicle width, which are
      smaller by an average of 30% and 20%, respectively. With the exception of the
      spinal canal depth, spinal canal area and pedicle width, all other parameters
      compared show a similar trend. The findings can provide more accurate modelling
      for analysis and spinal implant design and also allow more precise clinical
      diagnosis in sub-Asian groups.

PMID- 11956923
TI  - Spina bifida occulta in isthmic spondylolisthesis: a surgical trap.
AB  - An 11-year-old girl presented with symptomatic grade IIB isthmic type
      spondylolisthesis, with an elongated pars, confirmed on magnetic resonance
      imaging (MRI). Posterolateral in situ fusion of L5/S1 was performed. At surgery,
      a significant bony defect in the posterior aspect of S1 was noted. Awareness of
      this possible co-existence is paramount if iatrogenic damage to neural elements
      is to be avoided during surgery.

PMID- 11956924
TI  - Sacral extradural arachnoid cyst: a rare cause of low back and perineal pain.
AB  - Sacral extradural arachnoid cysts are rare. The clinical and radiological
      features of this condition are characteristic. One such rare case with low back
      and perineal pain is presented and the literature is reviewed. This patient
      presented with pain in the low back and perineal region, which was aggravated by
      standing, walking and straining. The patient also had numbness in both lower
      limbs, precipitated by standing and walking. Both the symptoms were relieved by
      lying down. Magnetic resonance imaging (MRI) revealed a sacral extradural
      arachnoid cyst. Sacral laminectomy with opening of the arachnoid cyst and
      ligation of the fistulous tract was done. Postoperatively, there was complete
      clinical recovery. Though rare, this entity should be considered in the
      differential diagnosis of low back and perineal pain. Surgical treatment is
      curative.

PMID- 11956925
TI  - Metastasizing chordoma of the lumbar spine.
AB  - Chordoma is a dysontogenetic bone tumour that appears in the region of the axial
      skeleton. Its malignant transformation has been underestimated in the past, since
      the incidence of metastasis is disputed. This paper describes a chordoma of the
      fifth lumbar vertebra, which at first was monolocular, but in the course of the
      disease led to a diffuse metastasis of the spine. Specific histological findings
      and the differential diagnosis of the chordoma are discussed, as well as previous
      descriptions in the literature relating to course, diagnosis, and therapy.

PMID- 11956926
TI  - Ideas and technical innovation: a guide for the aligned perforation of vertebral
      pedicles.
AB  - This report presents a guide for aligned perforation of vertebral pedicles. In
      multi-segment fixation of the spine there are technical problems with the
      placement of aligned pedicular screws when using rods of a wider diameter. To
      overcome this problem, a device has been developed to aid the placement of
      aligned pedicular implants along the longitudinal axis of the spine. The device
      consists of a track along which flat metal tabs containing orifices slide in both
      directions. The proximal and distal pedicles are first perforated by the standard
      technique and Kirschner or Steinman wires are passed through the tabs, fixing the
      device. The next step is the placement of the tabs in an appropriate position for
      the perforation of the remaining pedicles. These perforations can be made with
      drills or probes, according to the preference of the surgeon. After perforation,
      the Kirschner or Steinman wire is introduced in order to help fixate the device.
      This procedure is repeated until all pedicles have been perforated. The final
      steps involve the removal of the wires and of the device, and placement of the
      pedicular screws.

PMID- 11956927
TI  - Ventral cervical fusion at multiple levels using free vascularized double
      islanded fibula - a technical report and review of the relevant literature.
AB  - Reconstruction of the cervical spine using free vascularized bone flaps has been
      described in the literature. The reports involve either one level or, when
      multiple levels, they describe en bloc resection and reconstruction.
      Stabilization of different levels with a preserved intermediate segment with a
      single vascularized flap has not been described. We report on the case of a 55
      year-old man, who had been operated several times using conventional techniques
      for cervical myelopathy and instability, who presented to us with severe neck
      pain. Diagnostic procedures showed pseudarthrosis of C3/4 and stress-overload of
      the C3/4 and C5/6 segments. The C4/5 fusion was adequately rigid, but avascular.
      We performed anterior cervical fusion at the C3/4 and C5/6 levels with a
      vascularized fibula flap modified as a double island. The rigidly fused C4/5
      block was preserved and vascularized with the periosteum bridging the two fibular
      islands. The method and technique are described in detail. Fusion was adequate.
      Donor site morbidity was minimal and temporary. The patient is symptom free to
      date (25 months). The suggested method provides the possibility of vertebral
      fusion at different levels using a single vascularized flap. The indications for
      this procedure are (1) repeated failure of conventional methods, (2) established
      poor bone healing and bone non-union with avascular grafts and (3) a well-fused
      or preserved intermediate segment. The relevant literature is reviewed.

PMID- 11956929
TI  - The objectivity of whiplash.

PMID- 11956934
TI  - Endoscopic endonasal approach to the ventral cranio-cervical junction: anatomical
      study.
AB  - OBJECTIVE: In order to develop an endoscopic endonasal approach to the ventral
      cranio-cervical junction and odontoid process under the concept of a minimally
      invasive surgical strategy, a cadaver study was performed. METHODS: Sixteen
      artery-injected adult head specimens were used. Endonasal endoscopic approach was
      made through one- or two-nostril routes following the Jho's endonasal paraseptal
      technique. Rod-lens endoscopes, which were 2.7 or 4 mm in diameter, 18 cm in
      length with 0-, 30-, and 70-degree lenses, were used. RESULTS: Surgical landmarks
      leading to the craniocervical junction were the inferior margin of the middle
      turbinate, nasopharynx and Eustachian tube. The nasopharynx was readily
      identified following the inferior margin of the middle turbinate. The line drawn
      between the Eustachian tubes indicated the juncture between the clivus and atlas.
      With a midline mucosal incision, the ventral cranio-cervical junction was
      exposed. Odontoid resection was performed with removal of the anterior arch of
      the atlas. Clival resection can be performed as much rostral as required.
      Maneuverability of the surgical instruments was better with a two-nostril
      technique than with a one-nostril. Although the entire midline clivus was
      accessible rostrally, C-2 was the caudal limit through this endonasal route. A
      suturing device needed to be developed for mucosal or dural closure for live
      operations. CONCLUSION: This cadaver study demonstrates that an endoscopic
      endonasal approach to the ventral cranio-cervical junction and odontoid process
      can be a valid alternative to the conventional transoral approach.

PMID- 11956935
TI  - Delayed hydrocephalus after resection of supratentorial malignant gliomas.
AB  - BACKGROUND: To report our experience with 12 patients who developed delayed
      hydrocephalus after resection of supratentorial malignant gliomas. METHOD: The
      charts of all affected patients were analysed retrospectively for clinical
      presentation, time interval between initial operation and occurrence of
      hydrocephalus, neuroradiological findings, constituents of cerebrospinal fluid
      (CSF), surgical treatment, and outcome. FINDINGS: After initial good recovery
      following tumour resection all patients deteriorated secondarily due to
      development of hydrocephalus which was not encountered in the first postoperative
      CT-scans. Incidence is 3.4% overall and is 8.3% if exclusively calculated for
      frontal gliomas but increases to 15.2% if specified for patients with ventricular
      entry during tumour resection. Development of hydrocephalus is suggested to be
      due to proteinic precipitation since analysis of CSF revealed marked elevation of
      proteins in all patients. Whereas shunting of mere hydrocephalus yields
      satisfactory results outcome in cases of multiloculated hydrocephalus
      necessitating placement of multiple catheters is questionable. INTERPRETATION:
      Development of hydrocephalus after resection of malignant gliomas is not rare. It
      should be considered in patients with delayed deterioration after initial
      improvement. Outcome in relation to hydrocephalus is favourable in cases of mere
      communicating hydrocephalus, occurrence of multiloculated hydrocephalus, however,
      heralds a poor prognosis.

PMID- 11956936
TI  - Symptomatic pineal cysts: clinical manifestations and management.
AB  - Between 1991 and 2000, seven patients presented with symptomatic pineal cysts at
      our hospital (6 females, 1 male). Average age was 22 years (range 4-33 years).
      Headache was present in 6 patients, who were subsequently operated on. A scotoma
      and a transient inferior visual field deficit were minor signs in two patients
      respectively. A Parinaud syndrome with vertical gaze paralysis was found in none.
      In one child, paroxysmal pupillary dilatations and contractions ('springing
      pupils') constituted the only signs and a conservative policy was adopted. Four
      patients presented with hydrocephalus and were treated by an endoscopic resection
      of their pineal cysts (one stereotactically, three free-hand). Two other patients
      presented with a prolonged history of symptoms and signs: headache alone in one,
      headache with discrete neurological deficits in the other. Ventricles in these
      two patients were not dilated and therefore an open cyst resection by
      infratentorial supracerebellar approach was performed. Average follow-up in the
      six "operated" patients was 29 months (range 12-108 months). All four patients
      treated by endoscopy, are symptom-free at follow-up, whereas the two who were
      approached by open surgery, are not. Clinical presentation, radiological
      evaluation and treatment modalities of pineal cysts are discussed and compared
      with experiences reported in the literature. It is concluded that pineal cysts in
      the presence of obstructive hydrocephalus are a clear indication for endoscopy
      with a rigid endoscope.

PMID- 11956937
TI  - Slow pressure waves in the cranial enclosure.
AB  - Slowly varying pressure oscillations in the cranial enclosure are well known,
      especially intracranial pressure waves as best described by the pioneering works
      of Janny and Lundberg. Nevertheless, in spite of over twenty five years research
      on intracranial pressure waves, their origin and regulation remain unclear but
      are often considered only as pathological. Our aim was to review data on these
      phenomena to clarify their biological status and the role that they could play in
      the management of patients suffering from such intracranial neurosurgical
      diseases as intracranial hypertension, severe head injury, and hydrocephalus. It
      appears that these pressure waves reveal important information on the function of
      the cerebral vasculature and as such have significance for influencing
      intracranial compliance. Pressure waves are also closely associated with
      autoregulation, in particular dynamic autoregulation. It seems evident that they
      are not only pathophysiological but also physiological, linked with other
      biological parameters such as the neurovegetative cardiovascular system,
      breathing, and sleeping. This study shows that it is not only important to
      continue to explore these slow waves, but also the methods of analysis in order
      to more fully clarify their clinical significance.

PMID- 11956938
TI  - Quantitative local cerebral blood flow change after cerebrospinal fluid removal
      in patients with normal pressure hydrocephalus measured by a double injection
      method with N-isopropyl-p-[(123)I] iodoamphetamine.
AB  - The efficacy of cerebrospinal fluid (CSF) shunting surgery for normal pressure
      hydrocephalus (NPH) is difficult to predict. The CSF removal test is useful but
      quantification of the results is difficult. A method to quantitatively measure
      cerebral blood flow (CBF) by single photon emission computed tomography twice
      within 30 min after double injection of N-isopropyl-p-[(123)I] iodoamphetamine
      using a background subtraction method to correct for the temporal profile was
      utilized in tandem with CSF removal via a lumbar spinal tube in 22 patients of
      NPH to produce maps of baseline CBF and quantitative CBF change after CSF
      removal. All 22 patients with NPH underwent ventriculoperitoneal shunting surgery
      and were divided into two groups according to improvement in clinical symptoms
      and signs (responder group, N=15; nonresponder group, N=7). Baseline clinical
      characteristics and baseline CBF values were not significantly different between
      the two groups. Regional and whole brain CBF changes in the responder group
      (range 98-105%, whole brain 101+/-39%) were significantly higher than those in
      the nonresponder group (range 41-48%, whole brain 46+/-40%) (P<0.01).
      Discrimination analysis showed that an increase of more than 80% in CBF after CSF
      removal was predictive of response to shunt surgery with 77% accuracy. This new
      quantitative CSF removal test could be useful for selecting good candidates for
      CSF shunting surgery among patients with NPH.

PMID- 11956939
TI  - A clinical study of a fibrinogen-based collagen fleece for dural repair in
      neurosurgery.
AB  - BACKGROUND: There is frequently a need for dural grafts to cover defects
      resulting from retraction, shrinkage, or excision following neurosurgical
      procedures. Many substances have been tried as possible dural substitution, and
      different tissues and materials have been evaluated for use in dural repair.
      METHOD: The authors performed a retrospective review of 288 consecutive
      neurosurgical procedures using a fibrinogen based collagen fleece (TachoComb), a
      resorbable mesh of collagen from horse tendons, coated with human fibrinogen,
      bovine thrombin, bovine aprotinin and riboflavin (for marking the coated side),
      for dural substitution. The fibrinogen and thrombin imitate the last step of the
      coagulation cascade. On contact with bleeding wounds or other body fluids the
      coagulation factors dissolve and a link is formed between the collagen carrier
      and the wound surface. Thrombin converts fibrinogen into fibrin by splitting off
      peptides. Aprotinin prevents premature lysis of the fibrin clot by plasmin.
      FINDINGS: Neither superficial or deep wound infections nor aseptic meningitis
      were noted. We found good fibrous incorporation of TachoComb into the surrounding
      normal dura. Postoperative cerebrospinal-fluid (CSF) leaks developed in only five
      cases, who had to be re-operated, upon as well as one patient with a rebleeding.
      In another four cases, there was notable subcutaneous cerebrospinal-fluid
      accumulation without CSF-leak. They required a lumbar cerebrospinal-fluid
      drainage. INTERPRETATION: We conclude that TachoComb is a valuable alternative to
      the patients fibrous tissues for dural repair in cases in which autogenous
      tissues are either unavailable or insufficient for proper reconstruction.

PMID- 11956940
TI  - Versatile intraoperative MRI in neurosurgery and radiology.
AB  - BACKGROUND: Several models for the application of intra-operative magnetic
      resonance imaging (IMRI) have recently been reported, most of them unique. Two
      fundamental issues need to be addressed: optimal use of the scanner to ensure a
      wide base for research, development and clinical application, and an
      organisational model that facilitates such use. METHOD: While in our setting the
      IMRI project was initiated by the neurosurgeons, the need for wider use of the
      facilities was recognised since the beginning of the planning phase in 1996. An
      organisational model was developed that allowed for development of neurosurgical
      applications, radiological imaging, and radiological interventions and for the
      research and development work of the vendor. A resistive 0.23 T MR scanner was
      installed in a dedicated operating room environment. Unique to this scanner is
      the ability to turn off the magnet, allowing for normal OR activities and
      devices, and to turn on the magnet as needed with a relatively short six-minute
      ramp up time. A staged surgical technique was perfected, allowing for transfer of
      data to the neuronavigator outside the scanner during surgery. In neurosurgery,
      IMRI was used as one part of a neuronavigational system that included ultrasound
      imaging, intra-operative cortical stimulation during awake procedures,
      electrocorticography and two neuronavigators. FINDINGS: 34 neurosurgical cases
      included 27 brain tumour resections, 5 brain tumour biopsies, 1 extirpation of an
      arterio-venous malformation, and 1 haematoma evacuation. The scanner could also
      be used for normal clinical imaging where obese patients, children, claustophobic
      patients and postoperative control examinations were the major groups. The
      radiologists performed 110 interventions, including bone and abdominal biopsies,
      nerve root infiltrations and local pain therapies, with the optical needle
      tracking system under continuous MRI guidance. The organisational model allowed
      frequent use of the facilities for both neurosurgery and radiology and continuous
      development of the facilities. Intra-operative ultrasound was used in 20 tumour
      resections and in two open brain biopsies. This resulted in reduction of the
      number of MR imaging sessions during surgery. Five of the 27 resections were
      performed as awake craniotomies with cortical stimulation. For two of the
      resections, electrocorticography and depth electrode registrations were used.
      Furthermore, various non-MRI-compatible instruments and devices were used.
      INTERPRETATION: Intra-operative MRI is an imaging tool that can be useful
      especially in the context of neuronavigation. A scanner that can be turned off
      during surgery is particularly appropriate for neurosurgery. The concept of joint
      use of such facilities with other clinicians is mutually worthwhile.

PMID- 11956941
TI  - Movement artefacts and MR BOLD signal increase during different paradigms for
      mapping the sensorimotor cortex.
AB  - BACKGROUND: The authors evaluated the impact of motion artefacts on presurgical
      mapping of the sensorimotor cortex with functional magnetic resonance imaging
      (fMRI). Different mapping paradigms were compared with regard to the frequency of
      motion artefacts and the resulting signal increase. METHOD: 94 surgical
      candidates with mass lesions near the central region were investigated using
      BOLD(1)-contrast T2(*) weighted multislice multi-echo EPI gradient echo sequences
      on a 1,5 T Philips Gyroscan. Three functional paradigms were performed: a)
      repetitive self-paced clenching of the hand to a fist (68 runs); b) repetitive
      finger-to-thumb opposition (46 runs); c) sensory stimulation by repetitive
      brushing of the palm (15 runs). Task-related haemodynamic changes were identified
      by statistical analysis with the Kolmogorov-Smirnov-test. MR signal increase in
      percent was calculated for each of the paradigms. Motion artefacts were rated on
      a scale from 1 to 3. FINDINGS: Severe motion artefacts occurred in 8 hand
      clenching runs and in 2 finger opposition runs. Artefacts were more pronounced in
      hand clenching than in finger opposition. There were no motion artefacts in any
      of the sensory stimulation runs. Concerning the percent MR signal change there
      was no significant difference between hand clenching and finger opposition (T
      test: p>0,5) but a highly significant difference (p<0,0001) between both motor
      tasks and the sensory paradigm (hand clenching: 2.68+/-0.75; finger opposition:
      2.76+/-0.79; sensory stimulation: 1.72+/-0.65). INTERPRETATION: Sensory
      stimulation causes by far less artefacts than motor paradigms but it also has to
      be considered less sensitive as it produces a smaller MR signal increase.
      Therefore in presurgical evaluation sensory stimulation should be kept in reserve
      for cases in whom motion artefacts are very likely to occur, i.e. patients with
      severe forms of paresis.

PMID- 11956942
TI  - Department of Neurosurgery, Hacettepe University School of Medicine Ankara,
      Turkey.

PMID- 11956943
TI  - Hemorrhage within brain tumors in association with long air travel.
AB  - Two cases of hemorrhage within brain tumors after air travel are described. The
      hemorrhages occurred in a meningotheliomatous meningioma and in a melanoma
      metastasis after the patients had taken transatlantic flights lasting more than
      seven hours. The literature concerning bleeding associated with brain tumors is
      reviewed, and possible mechanisms by which air travel may have precipitated these
      hemorrhages, based on known physiological changes that occur in-flight, are
      discussed.

PMID- 11956944
TI  - Fusiform aneurysm of the posterior cerebral artery: report of two cases.
AB  - Two cases with fusiform aneurysm in the posterior cerebral artery are presented:
      The first one is a large fusiform aneurysm of the P(2) segment of posterior
      cerebral artery (PCA) in a 58 years old patient and the second a fusiform
      aneurysm of the P(3) segment of PCA in a 43 years old patient. The aneurysms were
      successfully treated the first by proximal ligation and the second by trapping of
      the aneurysm. The patients had no additional neurological deficits
      postoperatively and they are in an good condition, in four years and one year
      follow up respectively. The operative approaches and the radiological
      investigation in relation to the micro-anatomy of the posterior cerebral artery,
      as well as the outcome in these cases are discussed.

PMID- 11956945
TI  - Bilateral paramedian thalamic infarct in the presence of an unpaired thalamic
      perforating artery.
AB  - Bilateral paramedian thalamic infarction is rare. The suggested mechanism is
      occlusion of a central unpaired thalamic perforating artery--an anatomic variant.
      In the few existing reports of this condition, the diagnosis was based on
      computed tomography (CT) or magnetic resonance imaging (MRI) findings alone.
      Other causes of thalamic lesions were not ruled out, and there was no
      angiographic demonstration of the presumed variant artery. We present a case of a
      48-year-old man with a bilateral thalamic infarction seen on CT and MRI. Initial
      neurological examination revealed lethargy, severe combined motor and sensory
      aphasia, and a mild upward gaze limitation. The patient had no focal motor
      deficits. After 24 hours, the patient was more alert and his speech became more
      fluent, but Korsakoff-type amnesia with poor attention span became apparent. The
      patient improved slowly over 6 months of rehabilitation. Bilateral thalamic
      lesions can be caused by several conditions. Among those are thiamine deficiency,
      cerebral lupus, toxoplasmosis, cysticercosis, cerebral syphilitic gumma, and even
      tumors and fungal infections. All these were ruled out in our case.
      Superselective digital subtraction angiography (DSA) demonstrated a single
      unpaired thalamic perforator. To our knowledge, this is the first time this
      anatomical variant has been demonstrated in vivo in association with bilateral
      thalamic infarction.

PMID- 11956946
TI  - Cerebellar abscess due to Lactococcus lactis. A new pathogen.

PMID- 11956947
TI  - Post-traumatic transient bilateral trigeminal neuropathy.

PMID- 11956948
TI  - Effect of systemic L-DOPA administration on extracellular kynurenate levels in
      the rat striatum.
AB  - Dopaminergic stimulation, caused by direct dopamine receptor agonists or by
      indirectly acting agents such as d-amphetamine or methylphenidate, causes a
      functionally significant decrease in the concentration of kynurenate (KYNA), an
      astrocyte-derived endogenous antagonist of both N-methyl-D-aspartate (NMDA) and
      alpha7 nicotinic acetylcholine receptors, in the rat brain. The present study was
      designed to examine if this effect can be duplicated by the systemic
      administration of dopamine's bioprecursor L-DOPA. Experiments were conducted in
      unanesthetized rats, and the extracellular levels of KYNA were determined in
      striatal microdialysate samples. L-DOPA caused a dose-dependent, transient
      reduction in striatal KYNA, reaching a nadir of -37.5% 1.5 h after the
      administration of 200 mg/kg of the drug. This effect was abolished in animals
      with a 6-hydroxydopamine-induced lesion of the nigrostriatal pathway, but was not
      influenced by a prior striatal quinolinate lesion. These data confirm the
      dopaminergic control of striatal KYNA formation and suggest that the interactions
      are mediated by astrocytic dopamine receptors. This modulation of striatal KYNA
      levels might provide a link between dopaminergic, glutamatergic and cholinergic
      neurotransmission in the normal and diseased striatum.

PMID- 11956949
TI  - Inhibition of monoamine oxidase modulates the behaviour of semicarbazide
      sensitive amine oxidase (SSAO).
AB  - The specific activity and kinetic behaviour of semicarbazide-sensitive amine
      oxidase (EC 1.4.3.6; SSAO) towards benzylamine, in the rat heart, is affected by
      in vivo treatment with the non-selective monoamine oxidase (MAO) inhibitor
      tranylcypromine, but not by the selective MAO-A and -B inhibitors, clorgyline and
      lazabemide. SSAO activity was increased to 178% of control activity after 7 days
      of treatment with tranylcypromine. This increase appears to represent an increase
      in the limiting velocity (V(max)) for benzylamine oxidation with no significant
      change in the K(m) at that time-point. However, the K(m) for benzylamine
      oxidation was found to decrease in both controls and treated groups, in a time
      dependent manner, during the treatment regime. These findings suggest a link
      between SSAO and cellular stress and may have importance in the context of the
      recent finding that tissue-SSAO is identical to a vascular adhesion protein
      (VAP1), involved in the process of inflammation.

PMID- 11956950
TI  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) regulates
      survival of midbrain dopaminergic neurons.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member
      of the EGF-family of ligands signaling via the EGF-receptor tyrosine kinase. In
      the present study we show that HB-EGF which is expressed in close proximity of
      developing mesencephalic dopaminergic neurons promotes the survival of TH
      positive neurons in vitro. The survival promoting effect of HB-EGF is mediated
      via astroglial cells and utilizes the MAPK as well as the Akt-signaling pathway.
      Most notably endogenous HB-EGF significantly contributes to the survival of TH-+
      neurons in control cultures, suggesting a relevant developmental role of HB-EGF
      for dopaminergic neurons. These findings indicate that HB-EGF may be an important
      molecule for developing dopaminergic neurons of the ventral midbrain.

PMID- 11956951
TI  - Differences in brain area concentrations of dopamine and serotonin in Myers' High
      Ethanol Preferring (mHEP) and outbred rats.
AB  - Both male and female mHEP rats consume excessive amounts of ethanol and thus
      offer a rational model for examining biochemical and behavioral differences with
      non-drinking rat lines. Differences in basal concentrations of 5
      hydroxytryptamine (5-HT) and dopamine (DA) correlate with the consumption of
      ethanol in some ethanol-preferring rat lines. The concentrations of 5-HT and DA
      were examined by HPLC in five brain areas (prefrontal cortex, hippocampus,
      nucleus accumbens, striatum and hypothalamus) of ethanol-naive rats and after the
      oral administration of 0.25 or 1.0 g ethanol/kg in the male and female mHEP rat,
      the male Wistar rat, and the female Sprague-Dawley rat. The mHEP and control rats
      that received ethanol were screened for drinking in a 10-day "step-up" 3% to 30%
      ethanol solutions beginning at postnatal days 40 and 80, and then tested at 150
      days of age. The levels of DOPAC in females were lower in the hippocampus of both
      naive mHEP and ethanol-treated Sprague-Dawley rats. In striatum, the
      concentrations of 5-HT and DA were elevated in both mHEP and ethanol-treated
      Sprague-Dawley female rats. The concentrations of 5-HT and its metabolite, 5
      HIAA, were lower in the nucleus accumbens of the ethanol-naive female mHEP rat
      relative to the female outbred control. In the male rats, the levels of DA, HVA
      and DOPAC, as well as 5-HT and 5-HIAA were reduced in the hypothalamus of both
      ethanol-naive mHEP rats and Wistar rats receiving ethanol by gavage. These data
      demonstrate differences in neurotransmitter activity between the selectively bred
      mHEP rat and the outbred rat strains. There are few common features found in both
      the male and the female mHEP rat when compared to their respective controls.
      Differences in neurotransmitter function in these brain areas may account for
      some of the behavioral differences previously demonstrated between the two sexes
      of the mHEP rat.

PMID- 11956952
TI  - Effects of histamine H3 receptor agonist and antagonist on histamine co
      transmitter expression in rat brain.
AB  - The histaminergic H3-receptor (H3R) controls histamine synthesis and release in
      the tuberomamillary nucleus. We evaluated the effects of stimulating or blocking
      of H(3)R on glutamate-decarboxylase 67 kDa (GAD-67) and galanin mRNA expression,
      two histamine co-transmitters.After in situ hybridization histochemistry (ISHH),
      we observed a colocalization of 100% between histidine decarboxylase (HDC) and
      GAD-67 or H3R and of 80 to 97% with galanin. Adult rats received an H3R agonist
      ((R)alpha-Methylhistamine) or antagonist (ciproxifan) and were sacrificed 1 or 3
      hours later. Treatment effects on HDC, galanin and GAD-67 mRNA were studied by
      quantitative ISHH on serial sections. Treatment with the H3R agonist known to
      decrease histamine neuron activity initially reduced HDC and galanin gene
      expression but an inverse change, presumably reflecting a compensatory mechanism,
      was observed after 3 h on both markers. In contrast, the H3R antagonist known to
      activate histamine neurons, had opposite effects on the two markers, suggesting
      that co-transmitters are submitted to independent control mechanisms.
      Furthermore, GAD-67 mRNA levels were not significantly modified by these
      treatments.

PMID- 11956953
TI  - A novel grading scale for striatonigral degeneration (multiple system atrophy).
AB  - Striatonigral degeneration (SND) is commonly thought to represent the
      neuropathological substrate of L-Dopa unresponsive parkinsonism in patients with
      multiple system atrophy (MSA). Other neuropathological hallmarks of MSA include
      olivopontocerebellar atrophy (OPCA) and preganglionic sympathetic spinal cord
      lesions. Clinicopathological evaluation of MSA patients recruited into ongoing
      natural history studies or neuroprotective intervention trials will require
      standardized grading of MSA pathology. Based on 25 autopsy cases of MSA, we
      propose a novel SND grading scale which allows semiquantitative assessment of
      lesion severity based on neuronal loss, astrogliosis and presence of alpha
      synuclein positive glial cytoplasmic inclusions (GCIs) in substantia nigra,
      putamen, caudate nucleus, and globus pallidus. SND grade I is defined as
      degeneration of the substantia nigra pars compacta (SNC) with relative
      preservation of the striatum except for minimal gliosis and GCIs in the posterior
      putamen ("minimal change MSA"). SND grade II is characterized by neuronal loss,
      astrogliosis and presence of GCIs in SNC and posterior/dorsolateral putamen.
      Caudate nucleus and external globus pallidus may exhibit slight gliosis. Striatal
      pathology is severe and extends to anterior ventromedial subregions in SND grade
      III. There is neuronal loss in caudate nucleus and globus pallidus. GCIs are more
      abundant in grade II than grade III SNC and putamen. Preliminary
      clinicopathologic correlation studies suggest milder parkinsonian disability and
      better initial L-Dopa responsiveness in SND grade I and II cases compared to
      grade III cases. Prospective clinicopathologic studies are required to validate
      the proposed SND grading scale and may result in further subdivisions,
      particularly of SND grade III.

PMID- 11956954
TI  - Mutations of GCH1 in Dopa-responsive dystonia.
AB  - Dopa responsive dystonia (DRD) is an autosomal dominant dystonia caused by
      mutations in the gene GCH1 in about 50% of cases. GCH1 codes for GTP
      cyclohydrolase I, a rate limiting enzyme in the synthesis of tetrahydrobiobterin
      (BH(4)) from GTP. There is reduced penetrance and pronounced variation in
      expressivity of GCH1 mutations in families with DRD. Correlations between given
      mutations in GCH1 and phenotypes cannot be established. Mutations in GCH1 appear
      to function as dominant-negatives but the exact mechanism remains unclear.
      Additional open questions in DRD include the molecular mechanisms resulting in
      highly variable expressivity of symptoms and the more likely occurrence of
      symptoms in a female than in a male carrier of a GCH1 mutation.

PMID- 11956955
TI  - Impact of coexistent Alzheimer pathology on the natural history of Parkinson's
      disease.
AB  - OBJECTIVE: To assess the impact of coexisting Alzheimer (AD) pathology on the
      natural history of Parkinson's disease (PD). BACKGROUND: AD changes are
      frequently present in brains of demented PD patients. Assessing the relative
      contribution of AD pathology to the natural history of PD is difficult and the
      impact of both AD and cortical Lewy body (LB) pathologies on cognitive
      dysfunction is still under discussion. From clinical experience, dementia in PD
      patients, mainly related to AD pathology, is associated with a poor outcome, but
      the impact of AD pathology on the natural history of PD has not been studied
      systematically. MATERIAL AND METHODS: In 200 consecutive autopsy cases of PD (sex
      (m/f) ratio 1:1.1), age at death 58-98 (mean 77.0 +/- 9.5) years, from a
      specialized Austrian brain bank, retrospectively assessed major initial clinical
      symptoms (tremor, akinesia), moderate/severe dementia, and duration of illness
      were correlated with associated AD pathologies using CERAD, Braak and NIA-Reagan
      criteria. Mann-Whitney U-test, Cox-regression were used for statistical analysis.
      RESULTS: While gender had no influence on the clinical motor symptoms and
      outcome, tremor dominant type had a significantly better outcome than akinetic
      forms (p = 0.022), even after adjustment with age at onset and associated AD
      pathology (CERAD and Braak criteria). Patients with late onset showed
      significantly shorter duration of illness irrespective of dementia. Moderate to
      severe dementia, reported in 33% of the sample, was significantly correlated with
      AD pathology (all 3 criteria) that showed significantly negative correlation with
      survival: between CERAD 0-A vs. B and C there was a significant difference of odd
      ratios (p < 0.001), as was between Braak stages 0-2, 3-4.5, and 5, but not
      between Braak stages 3-4 and 5. CONCLUSIONS: The present data confirm previous
      studies suggesting better outcome of tremor-dominant than akinetic-rigid type of
      PD, significantly worse outcome in PD with late onset and dementia that is
      significantly correlated with coexistent neuritic Alzheimer pathology,
      particularly when using the CERAD and NIA-R criteria for the diagnosis of AD.
      Further studies are needed to elucidate the relative impact of cortical LB and AD
      pathologies on the natural history of PD.

PMID- 11956956
TI  - The brain insulin signal transduction system and sporadic (type II) Alzheimer
      disease: an update.
AB  - Nosologically, Alzheimer disease may not be considered to be a single disorder in
      spite of a common clinical phenotype. Only a small proportion of about 5% to 10%
      of all Alzheimer cases is due to genetic mutations (type I) whereas the great
      majority of patients was found to be sporadic in origin. It may be assumed that
      susceptibility genes along with lifestyle risk factors contribute to the
      causation of the age-related sporadic Alzheimer disease (type II). In this
      context, the desensitization of the neuronal insulin receptor similar to not
      insulin dependent diabetes mellitus may be of pivotal significance. This
      abnormality along with a reduction in brain insulin concentration is assumed to
      induce a cascade-like process of disturbances including cellular glucose,
      acetylcholine, cholesterol, and ATP associated with abnormalities in membrane
      pathology and the formation of both amyloidogenic derivatives and
      hyperphosphorylated tau protein. Sporadic Alzheimer disease may, thus, be
      considered to be the brain type of diabetes mellitus II. Experimental evidence is
      provided and discussed.

PMID- 11956958
TI  - Chronic treatments with tacrine and (-)-nicotine induce different changes of
      nicotinic and muscarinic acetylcholine receptors in the brain of aged rat.
AB  - The present study evaluated effects of chronic treatment with tacrine and (-)
      nicotine for 21 days on nicotinic and muscarinic acetylcholine receptors in the
      brains of old rats (24-25 months) by receptor autoradiography. The nicotinic
      receptor (nAChR) binding sites were measured by (-)-[3H]nicotine and
      [3H]epibatidine, and the muscarinic receptor (mAChR) binding sites by
      [3H]pirenzepine and [3H]AFDX 384. No change in (-)-[3H]nicotine binding was
      observed in all of the brain regions analysed following chroinic treatment with
      tacrine (10 mg/kg). Similarly, the [3H]epibatidine binding was not changed in
      most of the brain regions analysed except for a few brain regions where a
      decrease was observed in tacrine treated animals compared to control animals.
      Chronic treatment with (-)-nicotine (0.45 mg base/kg) significantly increased
      both (-)-[3H]nicotine and [3H]epibatidine bindings in every brain regions
      analysed except for the hippocampus when measured by (-)-[3H]nicotine. A
      significant decrease in [3H]AFDX 384 binding, but not in [3H]pirenzepine binding
      was observed in all of the brain regions analysed following the treatment with
      tacrine. These data suggest that chronic treatments with tacrine and (-)-nicotine
      differentially interfere and regulate the subtypes of nAChRs and mAChRs in the
      brain of aged rat. These data differ from what have been earlier observed in the
      brain of young adult rat following tacrine treatment, revealing some dynamic
      changes in receptor properties in the brain during aging.

PMID- 11956957
TI  - Effects of repeated administration of (-)-nicotine on AF64A-induced learning and
      memory impairment in rats.
AB  - It has been reported that pretreatment with (-)-nicotine prevents glutamate- and
      amyloid beta protein (Abeta)-induced cytotoxicity in vitro. However, few studies
      on the neuroprotective effects of (-)-nicotine in vivo have been reported. We
      examined whether repeated administration of (-)-nicotine exhibits neuroprotective
      effects in AF64A-treated rats. (-)-Nicotine (0.1 and 0.2 mg/kg, s.c.) was
      administered once a day for 28 days. On day 14, AF64A (2.5 nmol/side) was
      injected bilaterally into the hippocampus. Intrahippocampal injection of AF64A
      showed severe impairment of learning and memory in rats in the water maze and
      passive avoidance tests. Repeated administration of (-)-nicotine (0.1 and 0.2
      mg/kg, s.c.) did not reverse the impairment of memory induced by AF64A in the
      water maze test. Interestingly, the (-)-nicotine (0.1 and 0.2 mg/kg, s.c.)
      treated group showed weak impairment of learning and memory after AF64A treatment
      compared to the (AF64A + saline)-treated group in the passive avoidance test.
      These results suggested that (-)-nicotine may have neuroprotective effects
      against the neurotoxicity induced by AF64A.

PMID- 11956959
TI  - Combined analysis of CSF betaA42 peptide and tau protein and serum antibodies to
      glycosaminoglycans in Alzheimer's disease: preliminary data.
AB  - Neuropathological hallmarks of Alzheimer's disease (AD) are amyloid plaques and
      neurofibrillary tangles, containing betaA(42) peptide and tau protein,
      respectively. Amyloid plaques contain also glycosaminoglycans (GAGs). Whereas
      cerebrospinal fluid (CSF) levels of betaA(42) peptide and tau protein have been
      demonstrated as potential markers of Alzheimer's disease (AD), no data are
      available for GAGs. We determined (Elisa) tau and betaA(42) CSF levels, as well
      as serum antibodies to GAGs in 9 AD patients, and the values were analyzed in
      relation to age and severity of the disease. Beta-A42 and tau CSF levels were
      significantly reduced and increased, respectively, in AD patients when compared
      to controls, but they did not correlate with the severity of the disease. Despite
      their role in amyloidogenesis, we did not find evidence for the use of GAGs as
      diagnostic marker of AD.

PMID- 11956960
TI  - Involvement of dopamine in the progression of AIDS Dementia Complex.
AB  - HIV compromises immunological functions. Immune responses are regulated to a
      great extent by several molecules such as cytokines, neurotransmitters and
      hormones which interact with different immune effector cells and ultimately
      mediate the homeostatic responses to disease. Among these mediators, dopamine
      plays an important role. In this article we review AIDS Dementia Complex (ADC)
      and describe lines of evidence implying increased dopamine availability as a
      potent mediator of neurologic deficits in HIV infection and a factor exhibiting
      adverse effects on the progression of ADC.

PMID- 11956961
TI  - Partial dopamine agonists in the treatment of psychosis.
AB  - The discovery and characterization of dopamine in the mammalian brain earned Dr.
      Arvid Carlsson the Nobel Prize in 2000. Along with his many insights about
      dopamine pharmacology, came his proposal of the existence and critical role of
      dopamine autoreceptors in the overall regulation of dopamine-mediated
      neurotransmission. In this paper, the rationale, the putative mechanisms, and
      pertinent clinical data are reviewed to support the idea of the clinical
      relevance of dopamine agonists, especially partial agonists, in the treatment of
      psychosis. Evidence was gathered for the usefulness of this strategy in
      schizophrenia in early trials with apomorphine and N-propylnoraporphine (NPA).
      But clinical relevance was not a reality before the application of (-)-3PPP.
      These clinical results are presented. Moreover, now a partial dopamine agonist,
      aripiprazole, has been developed and will likely be marketed by BMS and Otsuka
      for the treatment of psychosis and will be the first drug in this class to be
      commercially available. Partial dopamine agonists represent the next new class of
      antipsychotic drugs, effective in treating schizophrenia.

PMID- 11956962
TI  - Developmental malformations in cerebral structures in "endogenous psychoses".
AB  - The last decades have revealed several structural deviances in patients with so
      called "endogenous psychoses". Reasonably well established are the enlargement of
      the lateral ventricles and subtle structural deficits in temporobasal and orbital
      frontal structures (hypofrontality) in a majority of schizophrenic patients. It
      is the aim of this investigation to examine the cytoarchitecture of these
      important central structures, namely the entorhinal region and the orbitofrontal
      cortex (Brodmann area 11) which have been under meticulous investigation in our
      laboratories over decades (for review: Beckmann, 2000).

PMID- 11956963
TI  - Preliminary evaluation of oral anticonvulsant treatment in the quinpirole model
      of bipolar disorder.
AB  - A potential model for bipolar disorder, quinpirole-induced biphasic locomotion,
      was used for a preliminary evaluation of behavioral effects of oral
      anticonvulsant treatment. Quinpirole, a D2/D3 agonist, induces a biphasic
      locomotor response starting with inhibition and followed by excitation,
      resembling the oscillating nature of bipolar disorder. The present study
      developed a paradigm for oral administration of anticonvulsants that resulted in
      therapeutic blood levels and tested the effects of treatment on the quinpirole
      induced response. Eleven days treatment with valproate (12 g/liter water),
      phenytoin (6 g/kg food), and carbamazepine (8 g/kg food) resulted in therapeutic
      blood levels and in a borderline significant reduction in quinpirole-induced
      hyperactivity without effects on the hypoactive phase. Valproate effects became
      more significant at the height of the hyperactivity response. Eleven days
      treatment with topiramate (30 mg/kg) resulted in a significant attenuation of
      quinpirole-induced hyperactivity, qualitatively similar to the effects of the
      other anticonvulsants. The results suggest that mood-stabilizing anticonvulsant
      drugs including topiramate may attenuate quinpirole-induced hyperactivity.

PMID- 11956964
TI  - Structure of the human histamine H3 receptor gene (HRH3) and identification of
      naturally occurring variations.
AB  - Neurotransmitter release is modulated by presynaptic histamine H(3) receptors
      located on histaminergic, noradrenergic and other nonhistaminergic neurons of the
      central and peripheral nervous system. Here, we report the determination of the
      structure of the human histamine H(3) receptor gene (HRH3) and the identification
      of a missense mutation (Ala280Val) in a patient with Shy-Drager syndrome. The
      coding region of the gene consists of three exons interrupted by two introns of
      approximately 1 kb in size. Exon boundaries only partly correspond to
      transmembrane domain organization. The homozygous Ala280Val variation in the
      third intracellular loop of the histamine H(3) receptor of a patient with Shy
      Drager syndrome may be related to the etiology of the illness due to altered
      norepinephrine release. Furthermore, knowledge of the gene structure allows the
      verification of alternative splicing of the receptor. The corresponding histamine
      H(3) receptor isoforms as reported for the guinea pig and rat histamine H(3)
      receptor in different brain regions are not found in the human brain.

PMID- 11956965
TI  - Molsidomine enhances the protective activity of valproate against
      pentylenetetrazole-induced seizures in mice.
AB  - Molsidomine (25 mg kg(-1)), a donor of nitric oxide, commonly used in the
      treatment of coronary artery disease, enhanced the protective activity of
      valproate against the clonic phase of pentylenetetrazole-induced seizures in
      mice, significantly reducing the ED(50) of valproate from 123.5 to 78 mg kg(-1).
      Molsidomine was found to be ineffective with respect to the protective action of
      clonazepam, ethosuximide and phenobarbital. Alone, molsidomine in a dose of 25 mg
      kg(-1) was ineffective in this model of seizures. Since N(G)-nitro-L-arginine, an
      inhibitor of nitric oxide synthase, failed to reverse the effect of molsidomine
      on valproate, an involvement of nitric oxide in the mechanism of the
      anticonvulsive efficacy of valproate does not seem to be probable. Molsidomine
      (25 mg kg(-1)) significantly elevated the free plasma level of valproate from
      33.8 to 46.2 microg ml(-1). Therefore, we conclude that the interaction of
      molsidomine with valproate is at the pharmacokinetic level. The combination of
      valproate with molsidomine appears beneficial because is free from adverse
      effects, in terms of motor impairment and long-term memory deficit. Our results
      suggest that the dosage of valproate in patients with coronary artery disease
      treated with molsidomine should be decreased. It would allow us to reduce adverse
      effects of valproate.

PMID- 11956966
TI  - The anti-Parkinson drug, rasagiline, prevents apoptotic DNA damage induced by
      peroxynitrite in human dopaminergic neuroblastoma SH-SY5Y cells.
AB  - Clinical trials for treatment of Parkinson's disease suggest that (-)deprenyl
      (selegiline), an inhibitor of type B monoamine oxidase, may slow the disease
      progression. However, the mechanism underlying protection of nigral dopamine
      neurons by selegiline remains an enigma. Recently, rasagiline, (R)(+)-N-propargyl
      1-aminoindan, was reported to be neuroprotective by in vivo and in vitro
      experiments, which is another selective irreversible inhibitor of type B
      monoamine oxidase and not metabolized into amphetamine-like derivatives as in the
      case of selegiline. In this paper, the mechanism of the neuroprotection was
      examined using human dopaminergic neuroblastoma SH-SY5Y cells against apoptosis
      induced by peroxynitrite generated from SIN-1. After treatment with SIN-1, the
      apoptotic DNA damage in the cells was quantified by a single cell gel
      electrophoresis (comet) assay and by staining with Hoechst 33342. Change in
      mitochondrial membrane potential, Deltapsim, was measured by use of a fluorescent
      indicator, JC-1. Rasagiline reduced apoptosis with much more potency than
      selegiline, and the protection required 20 min pre-incubation before SIN-1
      treatment. The protection by rasagiline was proved to be due to stabilization of
      mitochondrial membrane potential against the collapse induced by SIN-1, whereas
      rasagiline did not scavenge peroxynitrite directly. The studies on structure
      activity relationship showed that a propargylamine group and a hydrophobic group
      with an adequate intermediate space were required for the protection. These
      results suggest that rasagiline may protect declining neurons through its anti
      apoptotic activity in neurodegenerative diseases.

PMID- 11956967
TI  - Association analysis for genetic variants of the NMDA receptor 2b subunit
      (GRIN2B) and Parkinson's disease.
AB  - Recent studies have implicated N-methyl-D-aspartate (NMDA) receptor dysfunction
      in the pathogenesis and treatment of Parkinson's disease (PD). The NMDA receptor
      is composed of several subunits, of which, the receptor 2b subunit (GRIN2B) is of
      particular significance for PD. This subunit is found enriched in the basal
      ganglia, and PD-monotherapy potential has been determined for GRIN2B antagonists.
      For this study of a sample population consisting of 101 PD patients and 108
      controls, we tested the hypothesis that an ACC --> ACT transversion (2664(th)
      nucleotide of the coding sequence) affecting codon 888 (tyrosine) of GRIN2B
      confers susceptibility to PD, or relates to the age of onset. Comparing PD
      patients and controls, the distribution of the GRIN2B genotypes (p = 0.754) and
      alleles (p = 0.269) did not differ significantly. The onset age was not
      significantly different comparing the three genotypic groups (p = 0.189). Our
      negative findings suggest that it is unlikely that the GRIN2B C2664T polymorphism
      plays a substantial role in conferring susceptibility to PD in the Chinese
      population. Further studies with other genetic variations of NMDA subunits,
      relating either to PD or to the therapeutic response for PD, are suggested.

PMID- 11956968
TI  - A six-month multicentre, double-blind, bromocriptine-controlled study of the
      safety and efficacy of ropinirole in the treatment of patients with Parkinson's
      disease not optimally controlled by L-dopa.
AB  - OBJECTIVES: To compare the safety and efficacy of ropinirole and bromocriptine as
      adjunct therapy in patients with Parkinson's disease (PD) not optimally
      controlled by L-dopa. METHODS: A randomised, double-blind trial in which 555
      patients were assigned to three treatment groups according to the level of daily
      dosage of L-dopa, presence of motor fluctuations, and use of dopamine agonist
      before study entry. Patient response was defined as at least a 20% reduction in
      daily L-dopa dose plus: for patients with no prior treatment and no motor
      fluctuations, a 20% reduction in UPDRS motor score; for patients with motor
      fluctuations, a 20% reduction in time spent "off"; and for patients already
      taking an agonist, an improvement on the CGI scale. RESULTS: Safety assessments
      showed no significant differences in the two treatment groups for patients
      without prior dopamine-agonist therapy. In the group of patients with prior
      dopamine-agonist therapy, more patients reported adverse events in the ropinirole
      group (90% versus 79%, p < 0.001). The proportions of responders tended to be
      higher in ropinirole groups compared with bromocriptine groups and, in the
      subgroup with motor fluctuations, this difference was statistically significant
      (9.1% versus 0.0%, respectively; p < 0.05). CONCLUSIONS: Both drugs were well
      tolerated. In patients receiving a relatively high dose of L-dopa and requiring
      the addition of a dopamine agonist to control motor fluctuations or dyskinesias,
      ropinirole was significantly more effective than bromocriptine.

PMID- 11956969
TI  - Steele-Richardson-Olszewski-syndrome: the relation of dopamine D2 receptor
      binding and subcortical lesions in MRI.
AB  - We compared (123)I-iodobenzamide single photon emission computed tomography (IBZM
      SPECT) for imaging of striatal dopamine D(2) receptors in vivo, and MRI in 32
      patients with the clinical diagnosis of progressive supranuclear palsy (PSP). We
      found a significant inter-dependence of reduction of specific striatal IBZM
      binding indicative of striatal degeneration and of the absence of multiple signal
      hyperintensities in MRI; age had no influence neither on IBZM binding nor on
      signal hyperintensities. We conclude that the presence of multiple signal
      hyperintensities should raise doubt on the correct clinical diagnosis.

PMID- 11956970
TI  - Association of a polymorphism of the serotonin 1B receptor gene and alcohol
      dependence with inactive aldehyde dehydrogenase-2.
AB  - The use of persons who become alcoholic despite having a well-defined negative
      risk for alcoholism (inactive aldehyde dehydrogenase-2 or ALDH2) is advantageous
      in genetic research because of this population's reduced heterogeneity and
      possible genetic factors conferring susceptibility to alcohol dependence. This
      investigation of central serotonin neurotransmission, specifically the serotonin
      1B (5HT1B) receptor gene and its role in both regulating alcohol consumption and
      developing alcohol dependence revealed overrepresentation of the C allele of the
      861G > C polymorphism of 5HT1B in alcoholics with inactive ALDH2, compared with
      its frequency in nonalcoholic controls. No significant differences in 5HT1B
      genotype and allele distributions were observed between alcoholics with active
      ALDH2 and controls, however. Taken together with recent observations, these
      results suggest that genetic variability of the 5HT1B receptor is involved in the
      development of some type of alcohol dependence.

PMID- 11956971
TI  - Evaluation of the efficacy of antipsychotic attenuation of phencyclidine
      disrupted prepulse inhibition in rats.
AB  - SUMMARY: Phencyclidine reliably disrupts prepulse inhibition of the acoustic
      startle response in rats. Previous research has suggested that atypical
      antipsychotics (e.g., those that do not produce extrapyramidal motor effects)
      attenuate the disruptive effects of phencyclidine in this model whereas typical
      antipsychotics do not. Nearly all of this research has used the D2 antagonist
      haloperidol for comparison. In this study, antipsychotics with more diverse
      receptor binding profiles were tested for their efficacy in attenuating
      phencyclidine-induced disruption of prepulse inhibition. Results showed that
      phencyclidine disrupted prepulse inhibition in all groups of rats. Olanzapine,
      but not clozapine, attenuated this disruption, but this effect occurred only at a
      single (5 mg/kg) dose. None of the other antipsychotics nor spermine altered
      phencyclidine's effects. These results suggest that this model does not reliably
      differentiate between typical and atypical antipsychotics.

PMID- 11956972
TI  - Alzheimer's vaccine: a cure as dangerous as the disease?
AB  - Studies in transgenic mouse models of Alzheimer's disease suggested the potential
      for a vaccine development. However, some patients in the human clinical trials
      developed symptoms of brain inflammation, demonstrating the high risk of a
      deliberately induced auto-immune response.

PMID- 11956974
TI  - Kappa statistics in the assessment of observer variation: the significance of
      multiple observers classifying ankle fractures.
AB  - Studies using kappa statistics have been conducted with a varied but limited
      number of observers. The aim of this study was to evaluate the significance of
      multiple observers on kappa as a measure of observer variation. One hundred
      orthopedic specialists were asked to assess a random sample of ten sets of
      standard radiographs of 94 consecutive patients with ankle fractures. The
      observers were randomly allocated into four groups, which again were divided into
      subgroups with an increasing number of observers. Random subgroups of three
      observers revealed kappa values from 0.20 to 0.64 in the Lauge-Hansen and 0.27 to
      0.90 in the Weber classification system. With an increasing number of observers
      in the subgroups, kappa stabilizes around a mean value, indicating that the
      sampling variation and standard error decrease. The standard error found in this
      study makes kappa questionable as a measure for agreement among a small number of
      observers. Thus, kappa values obtained for a given diagnostic tool at one
      department are not directly comparable with results from other departments. We
      conclude that kappa cannot stand alone as a simple measure of observer variation.

PMID- 11956975
TI  - Diagnosis of thoracic outlet syndrome by magnetic stimulation of the brachial
      plexus.
AB  - The abductor pollicis brevis (APB) and abductor digiti minimi (ADM) compound
      muscle action potential (CMAP) latencies, and median and ulnar motor conduction
      velocities (MCVs), obtained by magnetic stimulation of the brachial plexus, were
      evaluated for the diagnosis of thoracic outlet syndrome (TOS). These measurements
      were compared in three groups of limbs: (1) the symptomatic limbs of patients
      with TOS (symptomatic group), (2) the asymptomatic con-tralateral limbs of these
      patients (asymptomatic group), and (3) the limbs of healthy control subjects
      (control group). Although no significant differences were observed in MCVs among
      the three groups, the APB CMAP latency in the sym-ptomatic group (12.0 +/- 1.2
      ms) was significantly prolonged compared with that in the control group (10.4 +/-
      0.64 ms; P < 0.01), and the ADM CMAP latency in the symptomatic group (11.0 +/-
      0.82 ms) was also significantly prolonged compared with that in the control group
      (10.1 +/- 0.59 ms; P < 0.01). The possibility is suggested that the evaluation of
      APB and ADM CMAP latencies by magnetic stimulation of the brachial plexus may be
      helpful for the diagnosis of TOS.

PMID- 11956976
TI  - Modified Desmanet's intramedullary pinning for fractures of the distal radius.
AB  - The purpose of this article is to present the results of Desmanet's
      intramedullary pinning for distal radius fractures, and also to present
      modifications of the cut-end management of pins; the cut-ends were shaped like a
      tear-drop for the radial pin and like a curtain-hook for the ulnar pin. One
      hundred and two operated patients (23 men and 79 women; mean age at operation,
      61.0 +/- 17.5 years) were followed up for 9.6 +/- 12.9 months. The clinical
      results were satisfactory according to the demerit point system of Saito; 83 were
      assessed as excellent and 19, as good. On the X-ray measurements, the mean values
      for radial inclination angle, volar tilting angle, and ulnar variance were 23.5
      degrees +/- 5.1 degrees, 8.8 degrees +/- 7.1 degrees, and 1.0 +/- 1.6 mm,
      respectively. Eighty-three patients (81.4%) showed no deformities. The results of
      23 aged patients (older than 75 years) were also satisfactory, and this method
      thus appears to be a good choice for aged patients with osteoporosis.
      Modifications of the cut-ends of pins reduced the extensor tendon complications
      that occur with Desmanet's original method. The present method is also good for
      extra-articular Colles' fracture. Concerning intraarticular Colles' fractures,
      the undisplaced type and the ulnar split type are good indications for this
      method. This method can also be used for the dorsal split depression type, but
      the ulnodorsal split type is not a good indication.

PMID- 11956977
TI  - Calcium phosphate bone cement for treatment of distal radius fractures: a
      preliminary report.
AB  - Distal radius fractures in osteoporotic patients are often complicated with a
      residual deformity and a subsequent stiff and painful wrist. The aim of this
      study was to evaluate the usefulness of calcium phosphate bone cement (CPC95) in
      the treatment of these fractures. Seven Colles type fractures in seven patients
      (all female; average age, 58 years) were treated. After a closed reduction, the
      fractures were fixed either by percutaneous pinning or by external skeletal
      fixation. The CPC95 was then injected into the cancellous bone defect through a
      small dorsal incision. The functional and radiological results were evaluated for
      up to 1 year. All patients were graded as good or excellent within 3 months, and
      all were graded as excellent at the final follow-up. The average duration of
      immobilization was 3.5 weeks. The overall shortening of the radius was 2.3 mm. In
      one patient, CPC95 extruded into the extensor tendon sheath and was surgically
      removed. Injection of CPC95 is a promising augmentation of osteosynthesis for
      distal radius fractures, although a prospective control study is mandatory to
      prove the usefulness of this material. The equipment and surgical technique
      should be refined to avoid the extrusion of CPC95.

PMID- 11956978
TI  - Carpal tunnel syndrome grading system in rheumatoid arthritis.
AB  - The grading system of Hashizume and Hirooka for carpal tunnel syndrome (CTS) was
      modified to refine the system for surgical treatment selection for specific
      subsets of CTS in patients with rheumatoid arthritis (RA). The grading system
      uses clinical signs and symptoms of CTS, including pain indications, to identify
      surgical subsets of patients to facilitate treatment selection. Retrospective
      analysis of the system included radiographic and electromyographic findings.
      Twenty-nine hands of 21 adult patients with CTS in RA were graded in the current
      study. Eight hands with mild synovitis received conservative treatment only.
      Endoscopic carpal tunnel release (ECTR), using Okutsu's universal subcutaneous
      endoscopic system with a clear cannula, was performed in 11 hands with moderate
      synovitis. Open carpal tunnel release (OCTR) combined with flexor tenosynovectomy
      was performed in 9 hands with severe synovitis. One more hand required OCTR after
      ECTR when malignant RA was diagnosed. Clinical results, evaluated using Kelly's
      criteria, were: excellent in 19 hands, good in 5, fair in 4, and poor in the 1
      patient with malignant RA. Clinical symptoms of CTS improved in all but the
      latter patient. Although the sample size in the current study is small, the
      results appear to warrant further study to determine the clinical utility of the
      grading system.

PMID- 11956979
TI  - Complications associated with bone cementing for the treatment of giant cell
      tumors of bone.
AB  - Aretrospective review was conducted of giant cell tumors treated between 1984 and
      1998 using the technique of aggressive curettage through a large bone window
      followed by acrylic cement reconstruction. Fifteen patients with a mean follow-up
      time of 46 months (range, 24-188 months) were identified. One patient had a local
      recurrence 24 months postoperatively. All the patients showed a radiolucent zone
      at the bone-cement interface up to 2.5 mm in width during the first 6 months
      after operation. However, the radiolucent zones were nonprogressive and did not
      affect the stability of the bone cement. Osteoarthritis of the knee joint
      occurred 14 years postoperatively in one patient with an intraarticular fracture
      at presentation. A stress fracture occurred in one patient who had the largest
      tumor in the distal femur. Acrylic cement reconstruction is a safe and effective
      procedure that provides local adjuvant therapy. Giant cell tumors with an
      associated intraarticular fracture remain a challenging problem to treat.

PMID- 11956980
TI  - The function of the psoas major muscle: passive kinetics and morphological
      studies using donated cadavers.
AB  - This study was carried out to analyze the phasic heterogeneity in the function of
      the psoas major muscle (PMM) depending on the flexion angle at the hip joint. The
      study design was a passive kinetic experiment using 25 osteoligamentous specimens
      with the PMM tendon. We measured the flexion angle of the hip joint where the PMM
      tendon loses contact with the femoral head and pelvic surface. Ten
      osteoligamentous specimens were used for additional measurements of the tensile
      force and pressure exerted on the PMM and/or at the bone-tendon interface when
      the PMM tendon was gently pulled in line with the PMM origin in the supine
      position. The tension loading the PMM tendon was measured at seven different
      angled positions of hip joint flexion (0 degrees, 15 degrees, 30 degrees, 45
      degrees, 60 degrees, 75 degrees, and 90 degrees ), using a load cell attached to
      a traction appliance. The pressure was measured at each of eight sites along the
      long axis of the PMM, using a pressure sensor. The PMM tendon lost contact with
      the femoral head at angled positions of 14 degrees (average) hip flexion, and
      lost contact with the iliopectineal eminence at positions of 54 degrees
      (average). The tension was stronger at angled positions of 0 degrees -30 degrees
      at the hip joint. The pressure on the femoral head and pelvic surface were
      stronger at positions of 0 degrees -30 degrees at the hip joint. The pressure on
      the femoral head was strongest at a hip flexion of 0 degrees. The tensile force
      markedly decreased at 45 degrees -60 degrees flexion at the hip joint, while the
      pressure on the femoral head gradually reduced to zero in the same phases. We
      concluded that the PMM works phasically: (1) as an erector of the lumbar
      vertebral column, as well as a stabilizer of the femoral head in the acetabulum
      at 0 degrees -15 degrees flexion at the hip joint; (2) less as a stabilizer, in
      contrast to maintaining its erector action, at 15 degrees -45 degrees; and (3) as
      an effective flexor of the lower extremity, at 45 degrees -60 degrees.

PMID- 11956981
TI  - Research on the effectiveness of intermittent cervical traction therapy, using
      short-latency somatosensory evoked potentials.
AB  - Short-latency somatosensory evoked potentials (SSEPs) were measured before and
      after intermittent cervical traction therapy to serve as objective indicators of
      therapy effectiveness. The subjects were 29 patients with myelopathy, 23 with
      cervical radiculopathy, 28 with cervical sprain, and 26 healthy individuals.
      SSEPs were recorded by stimulating the median nerve, and the negative potentials
      elicited from the brachial plexus (N9), neck (N11, lcN13, ucN13), and
      somatosensory area (N18) were measured to determine interpeak latencies and then
      corrected latency. As to the changes in SSEPs following traction, the N11-lcN13
      and lcN13-ucN13 interpeak latencies for patients with type I and II myelopathy
      decreased, and the severity of myelopathy was inversely related to the degree of
      decrease. The ucN13-N18 interpeak latency for some patients with severe
      myelopathy increased. The N9-N11 and N11-lcN13 interpeak latencies for patients
      with cervical radiculopathy decreased, and the ucN13-N18 for patients with
      cervical sprain accompanied by autonomic nervous symptoms also decreased.
      Traction therapy might improve conduction disturbance primarily by increasing the
      amount of blood flow from the nerve roots to the spinal parenchyma.

PMID- 11956982
TI  - Lack of posteromedial tibiofemoral congruence at full flexion as a causative
      factor in isolated medial meniscal tears.
AB  - The aim of the current study was to investigate posteromedial tibiofemoral
      congruence at full flexion of the knee in control knee joints and those affected
      by an isolated medial meniscal tear, to examine whether lack of such congruence
      was a causative factor in isolated medial meniscal tears. In this study, 1677
      knee joints in 875 subjects were evaluated. The joints were classified as a
      control group (1345 joints), an isolated medial meniscal tear group (224 joints),
      and a contralateral isolated medial meniscal tear group (108 joints).
      Posteromedial tibiofemoral congruence was examined on a lateral radiograph of the
      knee joint at full flexion. The tangent touching the anterior and posterior parts
      of the articular surface of the medial tibial condyle was assumed to be the X
      axis. To evaluate posteromedial tibiofemoral congruence, we measured the angle
      formed by the tangent that maximized the gradient of the tangent on the articular
      surface of the medial femoral condyle, and the tangent that maximized the
      gradient of the tangent on the articular surface of the medial tibial condyle.
      The mean angle differed significantly between the control and the isolated medial
      meniscal tear groups, regardless of sex. Isolated medial meniscal tears were
      found to be strongly related to an abnormally decreased angle, and, therefore,
      incongruence of the posteromedial tibiofemoral articulation at full flexion was
      considered to be one of the causes of isolated medial meniscal tears.

PMID- 11956983
TI  - Estimation of the rate of osteogenesis by tetracycline double labeling in
      intertrochanteric fractures of the femur in different age groups and its
      correlation with radiological grading of osteoporosis.
AB  - Our aim was to estimate the rate of osteogenesis by using tetracycline double
      labeling and to correlate it with the radiological grading of osteoporosis in
      patients of intertrochanteric fracture of the femur in different age groups.
      Thirty-two cases of intertrochanteric fracture of the femur of either sex,
      without any associated osteopenic conditions, who were admitted for surgery
      constituted the clinical material. The cases were divided into three age groups:
      group I, <45 years; group II, 45-60 years; and group III, >60 years. Osteoporosis
      was graded in all groups on plain X-rays by Singh's index (SI) and metacarpal
      index (MI). The patients were labeled with a single large dose (1.5 g) of
      tetracycline orally on day 1 and day 8. An iliac crest bone biopsy specimen was
      obtained from each of the patients during surgical intervention. Thin
      undecalcified sections were made by the hand grinding technique. The sections
      were studied under UV light for presence of fluorescence, and rate of
      osteogenesis (mineral appositional rate, MAR) was calculated for each of the
      groups. Only 7 patients were found to have radiological osteoporosis (by Singh's
      index). The average MI and MAR were found to be 46.5% and 1.48 microm/day,
      respectively. The single-dose labeling schedule has shown good fluorescent bands,
      comparable to the conventional dose schedule. No correlation was found between
      Singh's index and metacarpal index in group I and III, whereas in group II it was
      significant. There is no significant correlation between the rate of new bone
      formation and the radiological grading of osteoporosis.

PMID- 11956984
TI  - Significance of chondroitin sulfate isomers in the synovial fluid of
      osteoarthritis patients.
AB  - To test whether chondroitin sulfate (CS) isomers in synovial fluid are related to
      the radiographic severity of osteoarthritis (OA) and the age and sex, we
      investigated the concentrations of chondroitin 6-sulfate (C6S) and chondroitin 4
      sulfate (C4S) in patients with OA of the knee joint and age-matched healthy
      controls. Synovial fluid was obtained from 133 patients with OA of the knee and
      27 volunteers (controls). Twenty-seven patients were radiographically classified
      as grade 1, 59 as grade 2, 34 as grade 3, and 13 as grade 4 according to a
      modified version of the Kellgren and Lawrence scale. Compared with findings in
      the controls, values for the concentrations of C6S and C4S, and the C6 : C4S
      ratio, were significantly higher in the grade 1 patients, whereas in grade 3 and
      4 patients, the C6S concentration and the C6 : C4S ratio were lower. There was an
      obvious sex difference, and all values for the women were significantly lower
      than those for the men in both the control and the patient groups. In the control
      group, multiple regression analysis showed a moderate inverse correlation between
      age and all three of the above biochemical variables, and sex was moderately
      associated with the C6S concentration and the C6S : C4S ratio. In the patient
      group, age and sex showed a poor correlation with any of the three variables.
      However, the radiographic severity of OA showed a relatively strong inverse
      correlation with the C6S concentration and the C6S : C4S ratio, and a weak
      inverse correlation with the C4S concentration.

PMID- 11956985
TI  - Influence of aeration, storage, and rinsing conditions on residual ethylene oxide
      in freeze-dried bone allograft.
AB  - Bone allografts sterilized with ethylene oxide gas (EO) are used in the field of
      orthopedic surgery, and the reduction of the EO residual concentration is an
      urgent clinical matter. We therefore investigated the efficacy of aeration and
      the effects of varied preservation periods and rinsing conditions on the
      reduction of EO residuals in freeze-dried bone allografts in the present study.
      Before aeration, the EO residual level was 12.6 ppm, and, after the repeating of
      aeration at 60 degrees C once, two times, and three times, the level decreased to
      10.9 ppm, 3.1 ppm, and 0.47 ppm, respectively. Regarding the duration of
      preservation at room temperature, the mean EO residual level was 10.5 ppm, 4.9
      ppm, and 4.6 ppm, 1, 2, and 3 weeks after EO sterilization, respectively. By
      rinsing with physiological salt solution, the level was decreased to 6.9 ppm by 5
      min rinsing with 100 ml. Rinsing with 500 ml of this solution decreased the
      levels to 3.9 ppm, 2.8 ppm, and 2.0 ppm when done for 1, 5, and 10 min,
      respectively. Rinsing with 2000 ml of this solution decreased the levels to 3.6
      ppm, 2.6 ppm, and 1.7 ppm when done for 1, 5, and 10 min, respectively. These
      experimental results with chip bone allografts lead us to recommend repeated
      preoperative aeration and more than 2 weeks' preservation before use for reducing
      the residual EO concentration. It was also evident that intraoperative rinsing
      with 500 ml of physiological saline for 10 min reduced the EO residual level.

PMID- 11956986
TI  - Mechanical analysis of the lumbar vertebrae in a three-dimensional finite element
      method model in which intradiscal pressure in the nucleus pulposus was used to
      establish the model.
AB  - We established a three-dimensional finite element method (FEM) model of the 4th
      and 5th vertebrae, using computed tomography (CT) images (2-mm slice thickness)
      of a healthy 29-year-old man. Because of the lack of specific data regarding the
      material characteristics of the nucleus pulposus of intervertebral discs, we used
      intradiscal pressure in the nucleus pulposus to establish the model. We referred
      to data from Nachemson and from Sato et al. regarding intradiscal pressure and to
      the methods of Shirazi-Adl for data for other material characteristics (see text
      for these references). The mid-position model bears a load of 294 N in the
      vertical direction, while the models of the flexed and extended positions bear
      loads of 15 N-m. In addition, a degenerative disc model without intradiscal
      pressure was created for the standing model. The use of these models allowed the
      investigation of von Mises stress on the vertebral endplates and the annulus
      fibrosus. We also examined von Mises stress on the facet joint in normal and
      degenerative disc models. There was increased von Mises stress on the vertebral
      endplate in the anterior, center portions. von Mises stress on the annulus
      fibrosus increased in the posterior portion, the entrance to the neural foramen,
      and the exit of the neural foramen. von Mises stress was greater during flexion
      in the posterior portion; in particular, increasing to about 1.6 times the level
      seen with other postures. No changes were observed in von Mises stress on the
      vertebral endplates or annulus fibrosus in the degenerative disc model, but von
      Mises stress on the facet joints was about 2.5 times that seen in the normal disc
      model.

PMID- 11956987
TI  - A method of in-vitro measurement of the cross-sectional area of soft tissues,
      using ultrasonography.
AB  - Accurate measurement of the cross-sectional area of tendons and ligaments is
      essential in determining the mechanical properties of biological specimens. We
      measured these cross-sectional areas in rabbit specimens in vitro, using
      ultrasonography, in order to evaluate the usefulness of this method as a
      noncontact measurement technique. The cross-sectional areas of a rabbit's
      Achilles tendon, medial collateral ligament (MCL), and anterior cruciate ligament
      (ACL) were measured by means of ultrasonography, digital calipers, and
      computerized image analysis. For each of these three soft tissues, there was a
      high correlation between the values yielded by digital calipers and
      ultrasonography, and there was no significant difference in the values obtained
      by these three methods. Ultrasonography can detect the concavities on the surface
      of a specimen such as the ACL, because the shape of the specimen's transverse
      sonogram resembles its cross-sectional shape on a photograph. We concluded that
      the values yielded by ultrasonography were acceptable, and that ultrasonography
      is a useful noncontact measurement technique.

PMID- 11956988
TI  - Detection of the proliferated donor cells in bone grafts in rats, using a PCR for
      a Y-chromosome-specific gene.
AB  - Conventional corticocancellous bone grafts are known to revascularize gradually
      and to become repopulated with osteocytes and other types of cells. This study
      was conducted to study the origin of the cells found within conventional bone
      grafts as a function of time, using a new method which accurately identifies
      donor cells transplanted with the graft. The technique requires the
      transplantation of a 25-mm tibial diaphyseal bone graft from a male rat to a
      female isogenous recipient, placed anatomically in the tibia. The presence and
      relative proportion of cells containing the Y-chromosome (i.e., originating from
      the bone graft) was determined 4, 8, and 12 weeks after transplantation. At these
      times, genomic DNA was extracted from the grafted bones and a polymerase chain
      reaction (PCR) specific for the sex-determining region of the Y-chromosome (Sry)
      was performed, with appropriate controls. Sry-specific bands were evident in none
      out of three grafts at 4 weeks, two out of three at 8 weeks, and all grafts at 12
      weeks. These data demonstrate that not all cells within a conventional graft
      result from "creeping substitution" of necrotic bone. Instead, a small number of
      intrinsic cells from a nonvascularized corticocancellous structural graft survive
      and proliferate over time.

PMID- 11956989
TI  - Calcitonin gene-related peptide immunoreactive sensory DRG neurons innervating
      the cervical facet joints in rats.
AB  - The rat C5/6 facet joint is innervated multisegmentally from the C3 to the T3
      dorsal root ganglia. Sensory fibers from the C3, C4, and C7-T3 dorsal root
      ganglia were reported to be innervated nonsegmentally through the paravertebral
      sympathetic trunks, while those from the C5 and C6 dorsal root ganglia were
      reported to segmentally innervate the C5/6 facet joint. The presence of
      calcitonin gene-related peptide-immunoreactive nerve fibers has been proved in
      the facet joints, but their ratios have not been studied. Fluoro-gold-labeled
      neurons innervating the C5/6 facet joint were distributed throughout the dorsal
      root ganglia from the C3 to T3 levels. Of the fluoro-gold-labeled neurons, the
      ratios of calcitonin gene-related peptide-immunoreactive C3, C4, C45 C6, C7, C8,
      T1, T2, and T3 dorsal root ganglion neurons were 30%, 22%, 43%, 47%, 21%, 19%,
      25%, 36%, and 40%, respectively. The ratios of calcitonin gene-related peptide
      immunoreactive neurons in the C5 and C6 dorsal root ganglia were significantly
      higher than those in the C3, C4, C7, and C8 dorsal root ganglia. In the
      physiological condition in rats, the neurons of the C5 and C6 dorsal root ganglia
      may have a more significant role in pain sensation of the facets than other
      dorsal root ganglion neurons.

PMID- 11956990
TI  - Successful limb salvage of pathological fracture of the distal tibia caused by
      cancer metastasis.
AB  - Pathological fractures of the distal tibia as a result of cancer metastases are
      rare. In particular, the management of intraarticular fractures of the distal
      tibia has not been established. In this article, we present a case of
      pathological intraarticular fracture with an extensive bone defect of the distal
      tibia that was successfully treated by limb salvage with a locked intramedullary
      nail and pirarubicin-impregnated methylmethacrylate. A 52-year-old patient with
      duodenal cancer presented with a painful swelling in the left crus. The condition
      was diagnosed as an impending pathological fracture of the tibia because of
      cancer metastasis. During radiation therapy, an actual pathological fracture of
      the distal tibia occurred due to an accident. Limb-salvage surgery was performed
      by removing the metastatic lesion, followed by using a locked intramedullary
      nail. Three distal and seven proximal locking screws were inserted into the
      tarsal bones and the remaining tibia. About 10 cm of bone defect was
      reconstructed by pirarubicin-impregnated methylmethacrylate. Consequently, good
      stability was achieved. One month later the patient could walk without any aid.
      Postoperative functional score was 77% according to the Musculoskeletal Tumor
      Society criteria. There was no recurrence; however, the patient died of lung
      metastases 4 months after the limb-salvage surgery.

PMID- 11956991
TI  - Primary leiomyosarcoma of the femur.
AB  - Leiomyosarcoma usually arises in the uterus, gastrointestinal tract,
      retroperitoneum, or soft tissue. Primary leiomyosarcoma of bone is rare. We
      encountered two patients with primary leiomyosarcoma of the femur; one was a 24
      year-old woman and the other, a 41-year-old woman. Bone destruction observed on
      plain radiographs was minimal in both patients. Magnetic resonance imaging (MRI)
      showed low signal intensity on T1-weighted images and high signal intensity on T2
      weighted images, with these areas being much larger than the findings to be
      expected from the plain radiographs. Histological examination revealed spindle
      cell sarcoma, with an interlacing pattern, acidophilic cytoplasm and blunt-ended
      or "cigar-shaped" nuclei, in both patients. In both patients, immunohistochemical
      examination showed positive staining for vimentin, desmin, and alpha-smooth
      muscle actin. Extensive examination of the gastrointestinal tract and uterus
      revealed no primary lesion. Therefore, the leiomyosarcoma in the femur was
      considered to be primary rather than metastatic. Histological examination,
      including immunohistochemistry, and the exclusion of an extraskeletal primary
      lesion, is necessary in diagnosing primary leiomyosarcoma of bone.

PMID- 11956992
TI  - Intraosseous lipoma: a clinical study of 12 patients.
AB  - We studied 12 patients (13 bones) with intraosseous lipoma to elucidate the
      clinical features of this disease. The patients ranged in age from 14 to 54
      years. Eleven patients were men and 1 was a woman. The involved bones were the
      calcaneus in 6 patients (7 bones), humerus in 3, ischium in 2, and sacrum in 1.
      Three bones were in Milgram's stage I, 8 were in stage II, and 2 were in stage
      III. On plain radiographs, all bones showed a well-circumscribed radiolucent
      area. Nine bones showed calcification or ossification. Computed tomography or
      magnetic resonance imaging showed low density or high signal intensity,
      respectively, identical to the findings in normal adipose tissue. The tumor was
      curetted in 3 patients (3 bones), in whom local recurrence was not seen
      thereafter. In the remaining 9 patients (10 bones), we observed the natural
      course; in 1 of these patients, incisional biopsy was performed. During the
      follow-up period, only 1 patient showed slight enlargement of the lesion, while
      the findings in the others remained unchanged. Three patients had pain, which
      disappeared after the surgery or during the course of the observation. Partly
      because intraosseous lipoma tends to undergo spontaneous involution, and partly
      because diagnosis is easy from the radiological findings, surgery does not seem
      to be necessary in most patients.

PMID- 11956993
TI  - The role of survivin as a new target of diagnosis and treatment in human cancer.
AB  - Survivin has recently been identified as a novel inhibitor of apoptosis (IAP).
      Unlike other members of the IAP family, survivin is characterized by a unique
      structure that contains a single baculovirus IAP repeat and no really interesting
      new gene (RING) finger motifs, and it is expressed in many common human cancers,
      but not in normal tissues. Survivin regulates the G(2)/M phase of the cell cycle
      by associating with mitotic spindle microtubules, and it directly inhibits
      caspase-3 and caspase-7 activity. During tumorigenesis, survivin expression is
      inversely correlated with apoptosis inhibition and positively correlated with
      proliferation and angiogenesis. Inhibition of apoptosis by survivin predicts poor
      prognosis and shorter survival in human cancers. The molecular detection of
      occult cancer by the targeting of survivin as a novel molecular marker is useful,
      and micrometastasis detected by immunohistochemical staining for survivin reveals
      inhibition of apoptosis and the acceleration of cell proliferation. In in-vitro
      and in-vivo studies, survivin targeting with antisense and survivin mutants
      induces apoptosis, reduces tumor growth potential, and sensitizes cells to
      chemotherapeutic drugs and X-irradiation. These results suggest that survivin may
      have the potential to function as a new target for the diagnosis and treatment of
      cancer.

PMID- 11956994
TI  - Male germ cell death in mouse testes: possible involvement of Fas and Fas ligand.
AB  - Loss of germ cells is very common during various stages of mammalian
      spermatogenesis. Although cell death, particularly apoptosis, has been
      implicated, our understanding of the mechanisms underlying germ cell death is
      still limited. In order to elucidate the extent and mechanism of germ cell death,
      this review first covers what is known of germ cell degeneration in the normal
      testes of fetal, neonatal, and adult mice from electron microscopy (EM) and from
      terminal dUTP nick-end labeling (TUNEL) staining. The issue of whether the Fas
      and Fas ligand (FasL) system is involved in the induction of germ cell apoptosis
      in normal and damaged testes is then addressed, including consideration of both
      the ischemia-reperfusion model of testicular torsion and the estrogen-treated
      testis model of environmental endocrine disruption. Finally, this review proposes
      that different molecular pathways may be triggered to induce male germ cell
      apoptosis, depending upon the physiological and pathological states of the germ
      cells.

PMID- 11956995
TI  - A new marker for cup cells in the rabbit small intestine: expression of vimentin
      intermediate filament protein.
AB  - Cup cells in the intestinal lining in mammals are largely limited to the ileum,
      suggesting a specific but undetermined function. The investigation of these cells
      has been hindered by the lack of a suitable marker for immunohistochemistry. The
      small intestine of rabbits was examined for a potential molecular marker.
      Segments of New Zealand white rabbit small intestine, with and without Peyer's
      patches, were removed, rinsed, fixed with periodate-lysine-2% paraformaldehyde
      (PLP), and frozen for immunohistochemistry, or fixed in 2.5% glutaraldehyde
      solution for electron microscopy. The sections were stained with monoclonal
      antibodies (V9, 3B4) against vimentin, which is known to be absent in enterocytes
      other than antigen-sampling M cells, and observed by immunohistochemistry and
      immunoelectron microscopy. Epithelial expression of vimentin intermediate
      filament proteins was limited to a subpopulation of villus-associated cells and
      to cells over Peyer's patch domes. Immunoreactivity with vimentin antibodies was
      selectively found in cells with a cup-like indentation in the brush border in
      villous epithelium and in M cells in Peyer's patch follicle epithelium.
      Immunoelectron microscopy revealed that the labeled cells in villous epithelium
      had shorter microvilli than the adjacent absorptive cells, and small, sparse,
      mitochondria, which are ultrastructural characteristics of cup cells. Vimentin
      filaments were recognized in the area surrounding the nucleus and extending
      beneath the plasma membrane of cup cells. In rabbit small intestine, vimentin is
      useful for the detection of cup cells, as well as M cells, and may facilitate the
      investigation of these little understood cells.

PMID- 11956996
TI  - The pathogenesis of cerebrovascular lesions in hypertensive rats.
AB  - In this study we investigated the pathogenesis of hypertensive cerebrovascular
      lesions by light microscopy, immunohistochemistry, scanning electron microscopy,
      and transmission electron microscopy. The brains of rats with experimentally
      induced hypertension exhibited severe edema and intracerebral hemorrhage. Light
      microscopy of the arteries showed severe medial lesions and the deposition of
      fibrinoid substance in the intima. Immunohistochemistry showed that intercellular
      adhesion molecule (ICAM)-1, platelet-endothelial cell adhesion molecule (PECAM)
      1, interleukin (IL)-1alpha, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha
      endothelial cell expression was upregulated. Scanning electron microscopy of
      these arteries revealed the adhesion of neutrophils, monocytes, and a few
      platelets to endothelial cells, and their invasion of endothelial cell junctions
      and opened junctions. Transmission electron microscopy showed neutrophil and
      monocyte adhesion to the endothelial cells and neutrophil and monocyte invasion
      of endothelial cell junctions, intimal deposition of fibrinoid substance, and
      severe medial cell injury. Intravenously injected horseradish peroxidase
      insulated from endothelial cell junctions and, via pinocytotic vesicles, into the
      subendothelial space. These findings suggest that hypertension activates
      endothelial cells to increase the expression of adhesion molecules and cytokines,
      and induces neutrophil and monocyte adhesion and migration, resulting in
      endothelial cell injury and increased permeability of endothelial cells, which
      results in hypertensive arterial disease.

PMID- 11956997
TI  - Morphometric analysis, at electron microscope level, combined with hormone assay
      of nonfunctioning adrenocortical adenomas: comparison with aldosterone-producing
      adenomas.
AB  - We performed electron microscopic studies of eight nonfunctioning adrenocortical
      adenomas (NFA) and nine aldosterone-producing adenomas (APA) obtained from
      surgical specimens. A comparison of these two types of adenomas was conducted by
      morphometric analysis of random electron micrographs. The organelles measured
      included mitochondria (M), smooth-surfaced endoplasmic reticulum (SER), rough
      surfaced endoplasmic reticulum (RER), lipid vacuoles (LV), and lysosomes (Ly).
      The content of steroid hormones, including 17-alpha hydroxyprogesterone (17-OHP),
      aldosterone (Ald), and other steroid hormones, was measured in adenoma tissue
      from six NFA and eight APA. The percentages of the areas of the organelles M,
      SER, and RER per total cell area in the NFA were significantly lower than those
      in the APA. The average content of Ald in adenoma tissues in APA was markedly
      higher than that in the NFA, while the mean content of 17-OHP in the NFA was
      significantly higher than that in APA. In conclusion, NFA are morphometrically
      characterized by a reduction in organelles such as M, SER, and RER, compared with
      findings in APA. From the quantitative analysis of steroid hormones, it was
      suggested that NFA produce more precursor substances with less hormone activity
      than APA and that steroidgenesis in NFA is shifted to a glucocorticoid pathway,
      as indicated by the elevated 17-OHP concentration.

PMID- 11956998
TI  - High-resolution scanning electron microscopic evaluation of cell-membrane
      porosity by ultrasound.
AB  - The effect of low-intensity ultrasound on HL-60 cells (human promyelocytic
      leukemia cells) in the presence of the photo sensitizing drug merocyanine 540 (MC
      540) was evaluated morphologically, using a high-resolution scanning electron
      microscope and a transmission electron microscope. Exposure of HL-60 cells to
      ultrasound without MC 540 resulted in a decrease of finger-like processes in the
      cells. The cells showed many undulating ruffles on the surface. Distinct pits or
      holes in the membrane were not observed in these cells. The surface of HL-60
      cells treated only with MC 540 was relatively smooth compared with that of
      control cells. HL-60 cells exposed to ultrasound in the presence of MC 540 showed
      apparent surface deformation. Numerous crater-like depressions of heterogeneous
      dimensions were observed in many cells. In addition, various-sized pores were
      noted in the cell membranes of more damaged cells. These results indicate that
      cell degeneration was induced by a rapid change in cell membrane porosity during
      sonication in the presence of MC540.

PMID- 11956999
TI  - Use of oolong tea extract staining of soft-tissue specimens in low-vacuum
      scanning electron microscope with a cooling stage.
AB  - For direct observation of the surface structures of soft-tissue specimens, we
      examined rat tracheal tissue in a low-vacuum scanning electron microscope (SEM)
      equipped with a cooling stage. In specimens fixed with glutaraldehyde and osmium
      tetroxide, back-scattered electron images of the surface structure could not be
      clearly observed in the low-vacuum SEM because of the disruption of fine
      structures and a low signal-to-noise (S/N) ratio. Processing of the specimens in
      70% ethanol resulted in marked shrinkage, in contrast to results when processing
      in 30% ethanol. To overcome these problems, the trachea was initially fixed in
      2.5% glutaraldehyde (0.1 M phosphate buffer pH 7.4), treated with a mixture of
      0.2% oolong tea extract (OTE) and 2.5% glutaraldehyde, and postfixed in 1% osmium
      tetroxide. The sample was immersed in 30% ethanol and examined in a chilled SEM
      at -10 degrees C. The luminal coutour of the tracheal epithelial cells was
      clearly observed because of the decrease in shrinkage. Cilia of ciliated cells
      and microvilli of nonciliated cells were also clearly observed. These specimens
      also showed a high S/N ratio, thus allowing the observation of samples without
      the need for complete dehydration, critical-point drying, or metal coating. This
      OTE-incorporated conductive staining method is simple and rapid, and should prove
      to be highly useful for rapid SEM analyses of biological specimens.

PMID- 11957000
TI  - Cross-sectional magnetic resonance angiography is accurate in predicting degree
      of carotid stenosis.
AB  - Carotid stenosis is currently estimated using methods based on flow velocity or
      two-dimensional projection images. Manipulation of magnetic resonance (MR) images
      in three dimensions (3-D MR) allows for direct measurement of carotid artery
      cross-sectional luminal area. The objectives of this study were (1) to assess the
      accuracy of 3-DMR as a technique for estimating carotid artery stenosis, and (2)
      to compare 3-D MR results with estimates from duplex ultrasound sonography (DUS)
      and conventional angiography. Twenty-nine patients underwent rapid, contrast
      enhanced MRA within 1 month prior to carotid endarterectomy to obtain 3-D
      angiographic images of the carotid bifurcation. From these data, post-processing
      software was used to generate a longitudinal axis through the center of the
      vessel along which orthogonal cross-sectional images were taken. Luminal area
      measurements at the location of tightest stenosis and the distal normal internal
      carotid artery were obtained and used to calculate percent area stenosis.
      Applying the same procedure, 18 en bloc, ex vivo carotid plaques served as the
      standard against which we compared in vivo 3-D MR measurements at the location of
      tightest stenosis. Percent stenosis comparisons between MRA, angiography, and
      duplex ultrasound were also made. Our results showed that the measurement of
      luminal area by 3-DMR is accurate in predicting the degree of carotid stenosis.
      Direct measurement of luminal area may overcome limitations inherent to methods
      that rely on flow velocities and two-dimensional views of the carotid
      vasculature. A larger prospective study is necessary to confirm the reliability
      of this technique.

PMID- 11957001
TI  - Spontaneous superficial femoral artery dissection with distal embolization.
AB  - Primary arterial dissection of the peripheral vessels is a rare condition. We
      report a case of spontaneous dissection of the distal superficial femoral artery
      compounded by distal embolization leading to ischemic symptoms. The patient was
      successfully treated with exploration of the superficial femoral artery over the
      area of the dissection, distal embolectomy, and reconstruction by way of an
      interposition graft. Awareness of this condition leads to potentially earlier
      diagnosis and expands the therapeutic options.

PMID- 11957002
TI  - Does lower limb revascularization result in an improvement in sensory perception
      thresholds?
AB  - Patients with peripheral vascular disease are susceptible to neuropathy from
      chronic hypoxia. We wished to determine whether revascularization of chronically
      ischemic limbs results in any clinical changes in peripheral sensory thresholds.
      We prospectively measured quantitative vibration perception thresholds (VPT)
      using a Horwell neurothesiometer (in volts) in patients undergoing infrainguinal
      bypass, preoperatively and up to 6 month postoperatively. The bypassed limbs'
      preoperative VPT values were higher (lesser sensory perception) than the
      contralateral control limbs' preoperative values (mean score differences: 6 +/- 2
      and 4 +/- 10 at toe and foot levels respectively; p ? 0.004). Preoperative VPT
      values were not different from the 6-month postoperative values for the
      revascularized legs at toe and foot levels for all 55 patients (mean score change
      of ?0.84 and ?1.32, p > 0.5). The contralateral limbs' VPT values did not change
      significantly over the 6-month period (mean change scores of 2.9, p > 0.15, and
      2, p > 0.30, for toe and foot, respectively). A comparison of preoperative values
      between limbs that were eventually amputated and saved revealed no statistically
      significant differences. This study suggests that revascularization does not
      result in a clinically detectable improvement in sensory neuropathy. It may,
      however, prevent further degradation. The degree of preoperative neuropathy does
      not affect outcome in terms of limb salvage.

PMID- 11957003
TI  - Repair of a mycotic aneurysm of the infrarenal aorta in a patient with HIV, using
      a Palmaz stent and autologous femoral vein graft.
AB  - With the widespread use of endovascular surgery, aneurysms can be managed
      selectively with the use of stent grafts. Standard treatment of mycotic aneurysms
      usually requires resection and extraanatomic bypass. Although stent graft repair
      of a mycotic femoral aneurysm with autologous graft has been reported, we present
      a case of an infrarenal mycotic aneurysm in a patient with the human
      immunodeficiency virus (HIV) that was successfully treated with a novel
      endovascular approach.

PMID- 11957004
TI  - Gelatin-thrombin-based hemostatic sealant for intraoperative bleeding in vascular
      surgery.
AB  - Vascular surgical procedures may be prolonged because of intraoperative bleeding
      that is not easily controlled by cautery or suture ligation. This trial compared
      the ability of a new hemostat, FloSealTM Matrix (FM), with a known hemostat,
      Gelfoam(R) plus thrombin (GT), to control intraoperative bleeding. Patients
      undergoing vascular surgery procedures at four institutions were entered in the
      trial. After a bleeding site was identified, patients were randomized to one of
      the study agents: (1) FM, a cross-linked gelatin of bovine origin combined with
      thrombin, or (2) GT. The assigned agent was applied and the site observed for
      bleeding at 1, 2, 3, 6, and 10 min. The primary end point was cessation of
      bleeding within 10 min for the first identified site treated. Secondary end
      points were cessation of bleeding within 10 min for all sites and time to
      cessation of bleeding. Patients were assessed for morbidity at 30 days and 6-8
      weeks after the operation. Analysis was performed on an intent-to-treat basis for
      analysis of hemostasis at 10 min and on protocol-valid patients for analysis of
      time to hemostasis. From our results we concluded that for patients undergoing
      vascular surgery procedures, the new topical hemostat, FloSeal Matrix, provides
      more rapid and effective hemostasis than Gelfoam plus thrombin.

PMID- 11957005
TI  - Aortic mural thrombus embolization: an unusual presentation of essential
      thrombocytosis.
AB  - Hypercoagulable conditions are increasingly recognized as a causative factor in
      patients with thromboembolic phenomenon. Essential thrombocytosis (ET) is one
      such condition. This particular myeloproliferative disorder is most commonly
      associated with thrombotic complications of the microvasculature and bleeding
      complications involving mucosal surfaces (e.g., gastrointestinal tract bleeding).
      This case identifies an uncommon manifestation of ET-aortic mural thrombus
      leading to visceral embolism. Vascular surgeons should be aware of the diagnosis,
      treatment, and complications of ET, as patients with this condition may first
      present with an arterial occlusion.

PMID- 11957006
TI  - A selective approach to heparin use during elective abdominal aortic aneurysm
      resection: techniques, precautions, and advantages.

PMID- 11957007
TI  - End-to-end anastomosis in growing vessels using a novel suturing technique: VCS
      metallic staples.
AB  - For pediatric transplants, a suturing technique is needed that allows the vessel
      to grow along with better healing of the anastomosis, through eliminating
      exogenous and thrombogenic material in the intimal side, thus minimizing the risk
      of vascular stenosis. In this study, 12 55-day-old lambs were subjected to end-to
      end anastomosis of the right carotid artery and external jugular vein using
      vascular closure staple (VCS) clips (the vessels from the left side served as
      controls). Animals were followed up with duplex ultrasound. After 6 months,
      angiography was performed and animals were euthanized for microscopic study of
      the vessels. Duplex ultrasonography and angiography showed all vessels to be
      patent, with no flow disturbances and no stenosis at the anastomotic site at 6
      months. Stenotic segments caudal to the anastomosis site were seen in two veins.
      No significant changes were seen macroscopically in any of the veins, whereas one
      of the arteries developed a pseudoaneurysm at the anastomotic site. Histological
      structure was normal in all the studied veins. Arteries showed different degrees
      of modifications that did not affect patency or flow in any case. Measurements
      taken after 6 months confirm that this technique allows the vessel to grow. This
      technique may be useful in vascular pediatric surgery.

PMID- 11957008
TI  - Utility of intraoperative transesophageal echocardiography during endovascular
      stent-graft repair of acute thoracic aortic dissection.
AB  - This study was undertaken to evaluate the utility and efficacy of intraoperative
      transesophageal echocardiography (TEE) in the endovascular management of patients
      with acute type B aortic dissection. Twelve consecutive patients with acute type
      B aortic dissection underwent elective endoluminal stent-graft repair in the
      operating room under angiographic and TEE guidance. The follow-up protocol
      included spiral CT scanning before discharge from the hospital to assess
      thrombosis exclusion of the aortic false lumen, perfusion of branch vessels, and
      the absence of perigraft leak. No complications related to the use of TEE were
      encountered. TEE clearly demonstrated the presence and extent of the dissection
      flap in all patients. After the procedure a persistent perigraft leak or residual
      flow into the false lumen was diagnosed by TEE in 6 patients, whereas
      intraoperative angiography visualized only 3 cases. Postoperative CT scan
      confirmed these findings. One patient died 2 months later by aortic rupture
      secondary to a persistent perigraft leak not treated (8.3% mortality). No
      postoperative paraplegia or visceral ischaemia were registered, although an
      asymptomatic occlusion of left subclavian artery was observed. TEE monitoring
      detects perigraft leakage, identifies the entry tear, and accurately demonstrates
      sealing of the false lumen. TEE is essential in our practice as an adjuvant to
      fluoroscopy to achieve optimal results during endovascular stent-graft repair of
      acute thoracic aortic dissection.

PMID- 11957009
TI  - Management of carotid body paragangliomas and review of a 30-year experience.
AB  - Carotid body tumors are rare neoplasms and must be considered in the evaluation
      of all lateral neck masses; early surgical removal has been recommended. In this
      study, the medical records of 29 patients with 34 carotid body paragangliomas who
      were treated at our institution between 1971 and 2001 were retrospectively
      reviewed. An overview is provided of this lesion, including diagnosis,
      classification, metastatic potential, possible secretory function, operative
      techniques, and nonsurgical methods of management. Carotid body tumors may be
      familial and are more often bilateral in these instances; five patients (17%) had
      bilateral tumors in this series. The criterion for malignancy is demonstrated by
      metastatic tumor in lymph nodes or distant organs. Three patients (10%) had
      malignant tumors, one with hepatic metastases. One patient (3%) in our series
      exhibited abnormal serotonin production. Vascular reconstruction was necessary in
      eight cases (28%). No stroke occurred, however, two arterial thromboses (7%),
      five permanent cranial nerve deficits (17%), and one death (3%) from massive
      pulmonary embolism were seen. Our experience demonstrates that early operative
      management is warranted to avoid the possibility of eventual metastasis and
      progressive local invasion to the point of inoperability.

PMID- 11957010
TI  - Endovascular management of renal ischemia in a patient with acute aortic
      dissection and renovascular hypertension.
AB  - We report the endovascular management of a patient with a type B aortic
      dissection complicated by renal ischemia and resultant severe hypertension. A 69
      year-old male presented with acute type B aortic dissection with proximal
      extension complicated by severe renovascular hypertension secondary to left renal
      ischemia. Endovascular management consisted of imaging with intravascular
      ultrasound and left renal artery stenting with balloon-expandable stents. His
      hypertension subsequently resolved and he was discharged on his baseline two-drug
      regimen. Management of the ischemic complications of type B aortic dissections
      may be primarily approached using endovascular methods in stable patients, with
      open surgery reserved for those patients refractory to these methods. Patients
      with evidence of decreased renal perfusion represent a select group with an
      increased risk of associated morbidity and mortality and should therefore be
      aggressively managed. Accurate information and assessment of anatomy can be
      obtained with intravascular ultrasound and is therefore an important adjunct to
      the armamentarium of endovascular specialists managing complications of aortic
      dissection.

PMID- 11957013
TI  - Coexisting renal cell carcinoma and renal artery aneurysm.
AB  - We report a rare case of a patient with a renal artery aneurysm (RAA) and an
      ipsilateral renal cell carcinoma (RCC). This patient was treated with
      simultaneous aneurysmectomy and radical nephrectomy. The indications for surgical
      intervention for RAA remain controversial. We present a review of the literature
      on the clinical presentation, classification, etiology, and management of RAA and
      associated RCC.

PMID- 11957014
TI  - Utilizing granulocyte colony-stimulating factor to enhance vascular graft
      endothelialization from circulating blood cells.
AB  - Cells in the blood circulating through a vascular graft can contribute to
      endothelialization of its flow surface. We hypothesized that granulocyte colony
      stimulating factor (G-CSF) could enhance this process by increasing circulating
      bone marrow progenitor cells. Ten dogs received composite grafts that were
      shielded from any source of endothelialization other than the circulating blood.
      On the seventh postoperative day and for 7 days thereafter, five dogs were
      injected subcutaneously with 10 mg/kg/day of human G-CSF. The additional five
      dogs, used as controls, received no G-CSF. Grafts were retrieved at 4 weeks. All
      dogs recovered promptly postoperatively. White cell counts in G-CSF dogs
      increased by an average of 9.5-fold at the end of treatment, and had returned to
      normal before retrieval. All grafts remained patent. G-CSF grafts had
      significantly higher endothelialization than the controls (82.2 +/- 9.2% vs. 23.7
      +/- 4.4%, p = 0.0004), with extensive flow surface neointima, covered with a
      single layer of endothelium verified by FVIII/vWF and CD34 staining. Control
      grafts had virtually no neointima and were covered with a thin layer of fibrin
      coagulum. Significantly more endothelial-lined microvessels were also found in
      the G-CSF grafts than in the controls. Dogs treated with G-CSF have increased
      endothelialization of synthetic vascular grafts due to increased circulating bone
      marrow progenitor cells.

PMID- 11957015
TI  - Abdominal aortic coarctation, renovascular, hypertension, and neurofibromatosis.
AB  - Abdominal aortic coarctation and renal artery stenosis associated with
      neurofibromatosis is an unusual cause of renovascular hypertension in children
      and young adults. Sustained hypertension despite pharmacological treatment
      carries significant end-organ deterioration, failure to thrive, and potentially
      lethal complications. Timely arterial reconstruction can render these children
      normotensive, allowing normal development and reducing long-term morbidity.
      Progression of the arterial occlusive process, however, may occur after surgery.
      Therefore, careful follow-up is mandatory following aortorenal reconstruction in
      children with neurofibromatosis.

PMID- 11957017
TI  - Invasive aspergillosis in 2002: an update.
AB  - Despite significant advances in the management of immunosuppressed patients,
      invasive aspergillosis remains an important life-threatening complication. In the
      past two decades, the incidence of invasive aspergillosis in this population has
      continued to increase. Factors that predispose patients to develop invasive
      aspergillosis include prolonged granulocytopenia, the development of graft-versus
      host disease, immunosuppressive therapy, the use of adrenal corticosteroids, and
      the prolonged impairment of host defenses associated with diseases such as
      chronic granulomatous disease. Environmental factors also play a key part in the
      pathogenesis of this infection, and therefore, infection control measures play a
      critical role in reducing exposure of patients to Aspergillus. New exciting
      developments in the early diagnosis of invasive aspergillosis and the
      acceleration of antifungal drug discovery offer promise for the future.

PMID- 11957019
TI  - Prevalence, determinants, and molecular epidemiology of Streptococcus pneumoniae
      isolates colonizing the nasopharynx of healthy children in Rome.
AB  - The aim of this study was to determine the factors favouring Streptococcus
      pneumoniae nasopharyngeal colonization of healthy children attending daycare
      centres and to describe the circulation of penicillin-nonsusceptible strains
      using molecular techniques. A single nasopharyngeal swab was obtained from 610
      children attending daycare centres in the southeast area of Rome. Streptococcus
      pneumoniae isolates were serotyped, and antibiotic susceptibility was assayed by
      the E test. The genetic determinants of erythromycin resistance were detected by
      a duplex polymerase chain reaction, and the penicillin-nonsusceptible isolates
      were typed by pulsed-field gel electrophoresis. The overall carriage rate of
      Streptococcus pneumoniae was 14.9%. Living with more than three persons in the
      same household was the only risk factor statistically associated with carriage.
      Sixteen of 85 (18.8%) strains were nonsusceptible to penicillin, and 44 (52%)
      were resistant to erythromycin. Of the erythromycin-resistant strains, the vast
      majority showed a high level of resistance and carried the erm(B) gene. The
      penicillin-nonsusceptible strains belonged to six different serotypes; molecular
      typing showed that in only one case (2 strains) was there a circulation of the
      same clone in the same daycare centre. In view of the high rate of resistant
      Streptococcus pneumoniae strains, risk factors for carriage of resistant strains
      were evaluated. Children who received macrolides in the previous month had a
      higher risk of being colonized by macrolide-resistant strains as well as by
      strains resistant to both penicillin and erythromycin. Limiting the use of
      antibiotics in children seems the most appropriate measure to control the spread
      of antibiotic-resistant strains.

PMID- 11957018
TI  - Infections in renal transplant recipients receiving mycophenolate versus
      azathioprine-based immunosuppression.
AB  - Differences in the incidence, etiology, type, and outcome of infections occurring
      during the first 6 months after transplantation were evaluated in two consecutive
      cohorts of kidney recipients who received immunosuppressive regimens based on
      either azathioprine (plus antilymphocyte globulin, cyclosporine A, and
      prednisone) (ATG-AZA cohort) or mycophenolate-mofetil (plus cyclosporine A and
      prednisone) (MMF cohort). The overall incidence of infections in the two cohorts
      was similar (0.99+/-1.06 infections/patient in the MMF cohort and 1.04+/-0.99 in
      the ATG-AZA cohort, P=0.3), as was the incidence of bacterial and fungal
      infections. In patients who received mycophenolate, cytomegalovirus disease
      occurred at a higher incidence (0.3+/-0.54 vs. 0.1+/-0.34 episodes/patient,
      P=0.005) and affected the upper gastrointestinal tract more frequently (0.21+/
      0.48 vs. 0.025+/-0.16 episodes of cytomegalovirus ulcerative esophagitis,
      gastritis, or duodenitis per patient; P=0.001). A nonsignificant trend toward a
      higher recipient survival for patients receiving mycophenolate was noted (100%
      vs. 95%, P=0.07). In multivariate analysis, the following factors were
      independently associated with a higher risk of cytomegalovirus disease: the
      serostatus R-/D+ (seronegative recipients who received a kidney from a
      seropositive donor) (RR=35.7 [95%CI, 7.4-166.7]), treatment with mycophenolate
      (RR=10.4 [95%CI, 2.7-38.4]), and the development of any episodes of acute
      rejection (RR=10.1 [95%CI, 2.5-41.6]). These data show that kidney recipients
      receiving mycophenolate have a higher incidence of cytomegalovirus disease,
      mainly affecting the upper gastrointestinal tract, compared to those receiving
      azathioprine-based immunosuppression.

PMID- 11957020
TI  - Use of phenotyping and genotyping to verify transmission of Escherichia coli
      O157:H7 from dairy farms.
AB  - A total of 80 human infections by Escherichia coli O157:H7 were documented in
      Finland in 1997 and 1998. Most were sporadic and their sources undetermined. Five
      cases not associated with one another, one of which led to secondary transmission
      within a family, could be traced to five different dairy farms. These five case
      patients (age range 2-17 years, median age 3 years) were hospitalised with bloody
      diarrhoea; two of them developed haemolytic uraemic syndrome. All nine human
      isolates obtained were sorbitol negative, carried the verocytotoxin 2 and eae
      genes, and produced verocytotoxin and enterohaemolysin. The phage and pulsed
      field gel electrophoresis types of the human and bovine isolates from the
      corresponding farms were indistinguishable. The cattle (20-70 animals per farm)
      were monitored for up to 2 years after the human cases. The proportion of cattle
      excreting the type that caused the human infections varied from 3.2 to 66.7% when
      sampled soon after the human cases, and from 0.0 to 5.3% about a year or so
      later. On most of the farms, the animals excreted the pathogen intermittently. On
      one farm, Escherichia coli O157 isolates with other characteristics were also
      occasionally isolated. Although the infections were traced back to the farms, it
      could not be established whether the source was unpasteurised milk or direct or
      indirect contact with cattle. The results of this study emphasise the need for
      special recommendations for children visiting or living on a farm to prevent
      these infections.

PMID- 11957022
TI  - Differences between national reference laboratories of the European community in
      their ability to serotype Salmonella species.
AB  - The capacity of national reference laboratories of the European Union member
      states to correctly serotype Salmonella strains was assessed in four
      collaborative studies on serotyping in the period 1995-1999. Participants were
      asked to identify 20 strains in studies I, II and III and 16 strains in study IV,
      using the typing method routinely performed in their laboratory. In the first
      study, the strains to be identified belonged to Salmonella enterica subsp.
      enterica, salamae or houtenae, while in the other studies only strains belonging
      to Salmonella enterica subsp. enterica were included. Significant differences
      between laboratories and between studies were found. Differences were related to
      the frequency of actual occurrence of the study strains in the area served by the
      laboratory and the number of antisera available in the laboratory.

PMID- 11957021
TI  - Comparison of porphyrin-based, growth factor-based, and biochemical-based testing
      methods for identification of Haemophilus influenzae.
AB  - The accurate identification of Haemophilus spp. is essential for optimizing the
      role of the clinical microbiology laboratory in the diagnosis and management of
      Haemophilus infections. One laboratory-prepared medium and eight commercially
      available test systems were examined in parallel as a means of identifying 378
      clinical isolates of Haemophilus spp. as either Haemophilus influenzae or non-
      Haemophilus influenzae spp. At least one discordant result was noted with 187
      (49.5%) of the isolates tested. Discordant results were resolved either by
      majority rule for isolates with less than three discordant test results or by
      confirming the identity using conventional biochemical tests for isolates with
      three or more discordant test results ( n=20). Among these 20 isolates, 2 were
      judged not to belong to the Haemophilus genus. Comparisons of three porphyrin
      based methods, three growth factor-based methods (1 of which also incorporates a
      porphyrin testing component), and three biochemical-based methods revealed
      varying discrepancy rates within each testing method. In general, porphyrin-based
      methods, with overall discrepancy rates of 1.3% or less, outperformed other
      testing methods. One important exception was the performance of the porphyrin
      testing component of the Haemophilus Identification Test Kit (Remel, USA), which
      produced an overall discrepancy rate of 28.5% and a false-negative rate of 52.2%
      with non- Haemophilus influenzae isolates. Growth factor-based methods yielded
      overall discrepancy rates ranging from 1.6% ( Haemophilus Identification Agar
      Quad; Remel) to 10.4% (hemin and nicotinamide adenine dinucleotide disk component
      of the Haemophilus Identification Test Kit). Biochemical-based assays produced
      overall discrepancy rates ranging from 4.5% (API NH; bioMerieux Vitek, USA) to
      10.1% ( Neisseria Haemophilus Identification Card; bioMerieux Vitek).
      Collectively, these results suggest that porphyrin-based testing methods
      represent the most reliable means for identifying Haemophilus spp.

PMID- 11957023
TI  - Risk factors for breakthrough candidemia.
AB  - In order to assess the risk factors for breakthrough candidemia (candidemia
      occurring in patients receiving at least 3 days of systemic fluconazole or
      amphotericin B), 270 cases of candidemia occurring in two tertiary hospitals were
      analyzed. Using multivariate analysis, profound neutropenia (<100/mm(3)) (odds
      ratio [OR], 9.14), use of corticosteroids (OR, 3.17), and heavy antibiotic
      exposure (previous use of 2 or more antibiotics for at least 14 days) (OR, 2.93)
      were identified as risk factors. Neither the susceptibility of the isolates nor
      the presence of a catheter was found to be a risk factor. These data suggest that
      gastrointestinal colonization plays a major role in the development of
      breakthrough candidemia.

PMID- 11957024
TI  - Cerebrospinal fluid penetration and pharmacokinetic/pharmacodynamic parameters of
      intravenously administered colistin in a case of multidrug-resistant
      Acinetobacter baumannii meningitis.
AB  - Described here is a case of meningitis caused by multidrug-resistant
      Acinetobacter baumannii susceptible only to colistin, which was treated
      successfully with intravenous colistin sulfomethate sodium (5 mg/kg/day). The
      levels of colistin in serum and cerebrospinal fluid and the
      pharmacokinetic/pharmacodynamic parameters of colistin were determined. In this
      case, intravenously administered colistin penetrated cerebrospinal fluid (25% of
      serum levels) at levels sustaining bactericidal concentrations.

PMID- 11957025
TI  - Usefulness of PCR for diagnosis of imported malaria in Poland.
AB  - The aim of the present study was to use the polymerase chain reaction (PCR) to
      detect and identify Plasmodium spp. in diagnostic specimens, especially in those
      from patients diagnosed by microscopy as having possible mixed infections, and in
      those demonstrating low parasitemia or those that were parasite-negative. For
      most of the specimens, the PCR results were in accordance with microscopic
      findings, and in 16.2% of the cases with low parasitemia PCR enhanced the results
      by identifying the parasite species. This method detected one additional case of
      Plasmodium falciparum malaria among the patients with fever of unknown origin.
      The sensitivity of PCR for detecting Plasmodium DNA was found to correspond to
      1.35-0.38 and 0.12 for Plasmodium falciparum and Plasmodium vivax parasites per
      microliter of blood, respectively. Follow-up examinations demonstrated that most
      of the patients became negative for Plasmodium DNA from 1 to 4 days after the
      disappearance of parasitemia, as determined by examination of blood films. In
      conclusion, PCR performed by the reference laboratory significantly enhanced the
      microscopic diagnosis of malaria and proved very helpful in cases of low
      parasitemia and in cases of mixed infection.

PMID- 11957026
TI  - Comparative, clinico-epidemiologic study of Schistosoma mansoni infections in
      travellers and immigrants in Spain.
AB  - The study presented here aimed to contrast the marked clinical differences in the
      presentation of Schistosoma mansoni-induced infection between immigrants and
      travellers entering Spain from endemic regions, and to elucidate the therapeutic
      implications of these infections. A total of 200 African immigrants and 80
      travellers with schistosomiasis were included in the study. Among the immigrants,
      25 patients were diagnosed with Schistosoma mansoni infection; 15 presented with
      nonspecific symptoms, and 10 were asymptomatic. Hepatosplenomegaly was observed
      in nine. Among the travellers, 14 were diagnosed with Schistosoma mansoni
      infection; four were asymptomatic, four had Katayama syndrome, four had
      diarrhoea, and two had prostatitis. All of the patients were treated with
      praziquantel. Patients diagnosed with Katayama syndrome received praziquantel and
      dexamethasone for 3 days, with the praziquantel treatment being repeated at 3-4
      weeks. The significant differences observed in the clinical presentation of
      Schistosoma mansoni-induced infection, indicate that a well-differentiated
      therapeutic strategy is required when this infection is diagnosed in a non-immune
      (traveller) or a semi-immune (immigrant) patient.

PMID- 11957027
TI  - Use of a rapid immunochromatographic test for early diagnosis of dengue virus
      infection.
AB  - Acute serum samples collected from 92 patients were analysed for the presence of
      immunoglobulin M and G antibodies against dengue viruses using a rapid
      immunochromatographic (IC) test. Of 52 patients with dengue virus infection
      diagnosed using a standard hemagglutination inhibition test, 41 patients
      demonstrated dengue virus infection using the IC test. Half of the serum samples
      collected on day 3 after the onset of fever were positive for dengue antibodies,
      and all were positive on day 6 after symptom onset. In comparison with the
      hemagglutination inhibition test, the rapid IC test showed 79% sensitivity and
      95% specificity. The efficiency of the test was 86%. The IC test showed good
      agreement with the hemagglutination inhibition test (k=0.72). The IC test is
      quick to perform and provides early diagnosis of dengue virus infection.

PMID- 11957028
TI  - Sensitivity and specificity of ELISA and immunoblot for diagnosing
      neurocysticercosis.
AB  - In patients with neurocysticercosis (NCC), clinical manifestations and the
      results of neuroimaging procedures vary widely and often do not facilitate a
      definite diagnosis. In order to determine the value of immunodiagnosis for NCC,
      222 serum and cerebrospinal fluid samples from patients with NCC and healthy
      subjects were examined. The samples represented patients from various endemic
      regions, those with other neurological disorders from an endemic area (Mexico),
      persons with various helminth infections other than NCC, and a group of healthy
      volunteers. All specimens were tested by enzyme-linked immunosorbent assay and
      immunoblot for the presence of Taenia solium-specific antibodies. The
      sensitivities of the enzyme-linked immunosorbent assay and the immunoblot test in
      NCC patients were almost identical (80% and 81.7%, respectively). For both tests,
      the sensitivity was higher when cerebrospinal fluid (86%) was tested compared
      with serum (75%). The overall specificity of enzyme-linked immunosorbent assay
      was only 75.3% because of frequent false-positive results in patients with other
      helminth infections, especially in those with echinococcosis. The specificity
      (99.4%) of the immunoblot test was clearly superior. It is concluded that enzyme
      linked immunosorbent assay as a screening method and immunoblot as a confirmatory
      test contribute considerably to the diagnosis of NCC.

PMID- 11957029
TI  - Nocardia asteroides isolated from three patients with cystic fibrosis.
AB  - Over a 7-year period, three patients with cystic fibrosis had multiple sputum
      specimens that were smear- and culture-positive for Nocardia asteroides. Two of
      the patients had received long-term, low-dose inhalational corticosteroid
      therapy. Although all three patients were treated with cotrimoxazole, resulting
      in eradication of the organism from the sputum, there was no change in their
      clinical state, radiological findings, or pulmonary function. The isolation of
      Nocardia asteroides from the respiratory tract of cystic fibrosis patients is an
      unusual finding. Its presence does not necessarily imply disease, and in these
      three cases, it most likely represented colonisation. The clinical significance
      of Nocardia spp. isolated from the respiratory tract of cystic fibrosis patients
      needs to be considered in the context of the individual clinical picture.

PMID- 11957030
TI  - Successful treatment of prosthetic knee infection due to Campylobacter
      upsaliensis.

PMID- 11957031
TI  - Brain abscess due to Capnocytophaga species, Actinomyces species, and
      Streptococcus intermedius in a patient with cyanotic congenital heart disease.

PMID- 11957032
TI  - Macrolide resistance and distribution of erm and mef genes among beta-haemolytic
      streptococci in Hong Kong.

PMID- 11957033
TI  - Comparison of E test and double disk diffusion test for detection of extended
      spectrum beta-lactamases.

PMID- 11957034
TI  - Bactec 9240 alarm triggered by Plasmodium falciparum.

PMID- 11957037
TI  - Yet another new scientific journal?

PMID- 11957036
TI  - International strategy in the struggle against gastric cancer.

PMID- 11957038
TI  - Past victories, uncertainty, and reflections on the present and progress in the
      future.

PMID- 11957039
TI  - Detection and treatment of early gastric cancer in the West.

PMID- 11957040
TI  - Japanese Classification of Gastric Carcinoma - 2nd English Edition -
AB  - PREFACE: The first edition of the General Rules for Gastric Cancer Study was
      published by the Japanese Research Society for Gastric Cancer (JRSGC) in 1963.
      The first English edition [1] was based on the 12th Japanese edition and was
      published in 1995. In 1997, the JRSGC was transformed into the Japanese Gastric
      Cancer Association and this new association has maintained its commitment to the
      concept of the Japanese Classification. This second English edition was based on
      the 13th Japanese edition [2].The aim of this classification is to provide a
      common language for the clinical and pathological description of gastric cancer
      and thereby contribute to continued research and improvements in treatment and
      diagnosis.

PMID- 11957041
TI  - The new Japanese Classification of Gastric Carcinoma: Points to be revised.
AB  - SUMMARY OF CHANGES:1. The previous version described clinical, surgical and
      conclusive staging. This version retains clinical and surgical staging, being the
      staging before and during definitive surgery respectively. Conclusive staging is
      now defined as final staging, and may include information for which there is no
      histological proof (e.g. hepatic metastases). Pathological staging has been
      introduced, and requires microscopic proof.2. Lymph node staging has been
      extensively revised. A 3 tier system replaces the previous 4 tier system, and
      thus there are now 4 possible N stages (N0-3). The definition of some node
      groupings have been more precisely defined (No.11 and No.12).3. Lymph node
      dissection is classified D0-3 based on the new nodal groups. Minor modifications
      of the extent of dissection have been made. "Optional" stations have been
      omitted.4. Peritoneal cytology has been included in the staging system.6. Rules
      for staging carcinoma of the remnant stomach have been introduced.7. Rules to
      classify and evaluate endoscopic mucosal resection (EMR) have been introduced.8.
      Subclassification of T staging has been introduced for T1 (M and SM) and T2 (MP
      and SS) tumors.9. Nomenclature has been simplified: lower case letters are only
      used to define the "type" of staging (c clinical; s surgical; p pathological; f
      final). Tumor location is now defined as U (upper third), M (middle) or L
      (lower), replacing C, M, A. Proximal and distal margins are designated as PM and
      DM (previously OW and AW). LM and VM have been introduced for the lateral and
      vertical margins of EMR specimens.

PMID- 11957042
TI  - Cellular and molecular pathology of gastric carcinoma and precursor lesions: A
      critical review.
AB  - The cellular and molecular pathology of gastric cancer and its precursors are
      reviewed and discussed. Gastric carcinogenesis is a multistep phenomenon,
      beginning with precancerous conditions. Among these, adenoma is a direct
      precursor, because of the dysplastic nature of its cells. However, gastric
      adenoma is relatively rare. Chronic atrophic gastritis (CAG) is the most common
      precancerous condition, in which intestinal metaplasia often occurs. Carcinoma
      develops in CAG through stages of hyperplasia and dysplasia involving both
      metaplastic and non-metaplastic glands. Molecular alterations, including
      replication error and p53 and APC gene mutation and aneuploidy have been found in
      some of these conditions, confirming their role in carcinogenesis. Carcinomas of
      the stomach are heterogeneous in cellular composition. Both intestinal and
      gastric types of cells are found in all types of tumors, indicating the unique
      characteristics of gastric cancer. Many molecular lesions have been found in
      gastric carcinomas. Basic changes involve replication errors, telomerase
      activity, and aberrant CD44 transcripts. Many other changes often show
      differences in the frequency of their occurrence between the two major
      histological types of gastric carcinoma: well differentiated versus poorly
      differentiated, or intestinal type versus diffuse type. The timing and frequency
      of these changes in the stomach differ from the timing and frequency in colonic
      carcinogeneis. Pathological evaluation remains reliable and meaningful, in basic
      research as well as clinical management. To obtain correlation with molecular
      alterations, the need for detailed pathologic classification of gastric carcinoma
      is recognized, taking into account its biologic behavior and grades of cell
      differentiation.The cellular and molecular pathology of gastric cancer and its
      precursors are reviewed and discussed. Gastric carcinomas are unique in their
      heterogeneity in both cellular composition and molecular changes.

PMID- 11957043
TI  - Early gastric cancer: Report of 58 cases.
AB  - BACKGROUND: This retrospective study was carried out to review our surgical
      experience and to define the clinicopathologic profile of early gastric cancer in
      a Western country with one of the highest incidences in the world.METHODS: Fifty
      eight patients who had gastric surgery for early gastric cancer were included in
      this study.RESULTS: The incidence of early gastric cancer was 13.9% of the
      patients with resected gastric cancer (58/416). The mean age of these 58 patients
      at diagnosis was 56.8 +/- 12.3 years (range, 30-81 years) and the male: female
      ratio was 2.4 : 1. The most common presenting symptom was epigastric pain
      (52.4%). All patients were treated by surgical resection. Tumors were typically
      located in the antrum (72.4%), with a predominance of lesser curvature lesions
      (89.7%). Macroscopically, the majority of the lesions (63.8%) were excavated
      (types IIc and III). Thirty tumors were intramucosal and 28 extended into the
      submucosa. Thirty were of the intestinal type and 28 of the diffuse type. The
      rate of regional lymph node metastasis was 10.4%. The overall 5-year survival
      rate was 93.9%.CONCLUSIONS: The excellent response to surgical resection of early
      gastric cancer reported by Japanese authors is reproducible in Western countries
      even in the presence of regional lymph node metastasis. For this reason an
      aggressive surgical approach should be taken for all early gastric cancer.

PMID- 11957044
TI  - Effects of super-extended paraaortic lymphadenectomy (PAL) on biological
      responses in totally gastrectomized patients with T3 or T4 gastric cancer.
AB  - BACKGROUND: In Japan, much attention has recently been paid to super-extended
      paraaortic lymphadenectomy (PAL) for the treatment of advanced gastric cancer.
      However, it has been reported that PAL is associated with increased morbidity and
      mortality, as compared to conventional extended lymphadenectomy (D2 or D3).
      Therefore, an analysis of the effects of PAL on perioperative changes in the
      biological responses of patients essential for determining the potential utility
      of this procedure.METHODS: The current non-randomized prospective study included
      evaluations of perioperative changes in parameters of surgical stress (series I;
      serum levels of antidiuretic hormone, interleukin-6, trypsin, and phospholipase
      A(2)) and immunocompetence (series II; phytohemagglutinin- and concanavalin A
      induced blastogenesis, activity of natural killer cells and the ratio of CD4
      cells to CD8 cells) in patients with advanced gastric cancer (T3 or T4),
      comparing groups treated with D3 plus PAL ( n = 12) and D3 ( n = 13), and a
      control group with early gastric cancer ( n = 16) treated with D1 lymphadenectomy
      (perigastric N1 nodes) between April 1995 and April 1997.RESULTS: The duration of
      surgery and the amount of blood lost were longer and greater in the D3 plus PAL
      group than in the D3 and D1 groups. D3 plus PAL and D3 were associated with
      significant postoperative increases in parameters of surgical stress, as well as
      with significant postoperative immunosuppression, compared to results with D1.
      However, there were no significant differences in the respective parameters
      between the D3 plus PAL and D3 groups.CONCLUSIONS: Our results indicate that
      there are no essential differences in patients' biological responses between D3
      plus PAL and D3 lymphadenectomy. It appears that PAL-associated morbidity can be
      minimized by very careful manipulation during the dissection of paraaortic lymph
      nodes.

PMID- 11957045
TI  - Clinicopathological study of gastric carcinoma in high- and low-mortality
      countries: Comparison between Japan and the United States.
AB  - BACKGROUND: Gastric carcinoma is a tumor that shows marked differences in
      geographic distributions. The incidence of the gastric carcinoma has been falling
      dramatically in Western countries. In sharp contrast, the incidence in Japan is
      still quite high.METHODS: A comparative clinicopathological study was performed,
      examining gastric carcinomas in 978 Japanese patients (Tokyo) and 157 United
      States patients (San Diego), that had been surgically resected over the 11-year
      period 1980-1991.RESULTS: The median age of US the patients (64.1 years) was
      higher than that of the Japanese patients (59.0 years). There was no difference
      in the sex ratios. Forty-five of the Japanese patients had early gastric cancer,
      while this occurred in 10% of the US patients. In terms of tumor location, 47%
      were in the upper portion of the stomach in the US patients, while, in contrast,
      this proportion in Japanese patients was 23%. In association with the marked
      difference in tumor location, 36.5% of the US patients underwent operations with
      the thoraco-abdominal approach, while this approach was used in 7.5% of the
      Japanese patients. The distribution of histological types was similar in the two
      countries' samples. There was also no significant difference in the distribution
      of the histological types in the same age groups in the two countries' samples.
      The rate of the well differentiated type increased with age while the rate of
      poorly differentiated type decreased. In US patients, 35.8% had marked neural
      invasion, while this occurred in 8.5% of Japanese patients.CONCLUSION: This study
      revealed marked differences in the features of gastric cancer between the US and
      Japan in terms of tumor location and surgical procedures.

PMID- 11957046
TI  - Expression of HLA-DR and urokinase-type plasminogen activator in stage IV gastric
      cancer.
AB  - BACKGROUND: Some patients with stage IV gastric cancer have a long survival. Host
      immune response and proteolytic activity in the primary tumor may be associated
      with outcome in these patients. The purpose of this study was to assess
      prognostic factors in patients with stage IV far advanced gastric cancer.METHODS:
      Findings in 26 patients who underwent resection of stage IV gastric cancer were
      retrospectively analyzed for clinicopathological variables, and for the
      immunohistochemical expression of human leukocyte antigen (HLA)-DR as an index of
      host immune response and for expression of urokinase type-plasminogen activator
      (u-PA) as an index of proteolytic activity in the tumor.RESULTS: Of the 13
      clinicopathological and immunohistochemical variables tested by univariate
      analysis surgical curability, lymph node metastasis, HLA-DR expression, and u-PA
      expression had a significant influence on survival after surgery. Multivariate
      analysis showed that surgical curability, HLA-DR expression, and u-PA expression
      independently influenced survival. Patients positive for HLA-DR expression [HLA
      DR (+)] and regative for u-PA expression [u-PA (-)] had the best survival: 25
      month median survival and 25% 5-year survival rate. Patients who were HLA-DR (+)
      and u-PA (+), or HLA-DR (-) and u-PA (-) had a median survival of 10 months, a 1
      year survival rate of 46.2%, and a 2-year survival rate of 7.7%. HLA-DR (-) and u
      PA (+) patients had the worst survival: 4.5-month median survival and 0% 1-year
      survival.CONCLUSIONS: These findings suggest that host immune response and
      proteolytic activity in the primary tumor may determine malignant potential, and
      that the combination of positive-HLA-DR and negative-u-PA expression in cancer
      cells may be a predictor of prolonged survival in stage IV gastric cancer
      patients.

PMID- 11957047
TI  - Gastric tube reconstruction prevented esophageal reflux after proximal
      gastrectomy.
AB  - Although the standard operation for early cancer of gastric cardia is proximal
      gastrectomy followed by jejunal interposition, we recently reported a simple and
      useful technique for proximal gastrectomy with gastric tube reconstruction. The
      operative procedures included resection of the proximal two-thirds of the
      stomach, followed by anastomosis between the esophagus and gastric tube, using a
      circular stapler (Proximate ILS 25; Ethicon, Cincinnati, OH, USA). The gastric
      tube was about 20 cm long and 4 cm wide. The patient a 76-year-old man had no
      reflux symptoms such as heartburn, retrosternal pain, and regurgitation.
      Endoscopy showed no evidence of reflux esophagitis, including mucosal redness,
      erosion, and ulceration. Ambulatory 24-h pH monitoring indicated that the pH of
      the lower esophagus was between 6 and 8 when the patient was upright and between
      5 and 7 when he was in the supine position. There were nine reflux episodes
      during the day, and no reflux episode while he was asleep. The duration of each
      reflux episode was less than 1 min, and the total reflux time was 1 min in the 12
      h day (0.1%). These data indicate that reconstruction by gastric tube may prevent
      esophageal reflux in patients who have undergone proximal gastrectomy for early
      cancer of the gastric cardia.

PMID- 11957048
TI  - Long-term survival after perforation of advanced gastric cancer: Case report and
      review of the literature.
AB  - Although the standard operation for early cancer of gastric cardia is proximal
      gastrectomy followed by jejunal interposition, we recently reported a simple and
      useful technique for proximal gastrectomy with gastric tube reconstruction. The
      operative procedures included resection of the proximal two-thirds of the
      stomach, followed by anastomosis between the esophagus and gastric tube, using a
      circular stapler (Proximate ILS 25; Ethicon, Cincinnati, OH, USA). The gastric
      tube was about 20 cm long and 4 cm wide. The patient a 76-year-old man had no
      reflux symptoms such as heartburn, retrosternal pain, and regurgitation.
      Endoscopy showed no evidence of reflux esophagitis, including mucosal redness,
      erosion, and ulceration. Ambulatory 24-h pH monitoring indicated that the pH of
      the lower esophagus was between 6 and 8 when the patient was upright and between
      5 and 7 when he was in the supine position. There were nine reflux episodes
      during the day, and no reflux episode while he was asleep. The duration of each
      reflux episode was less than 1 min, and the total reflux time was 1 min in the 12
      h day (0.1%). These data indicate that reconstruction by gastric tube may prevent
      esophageal reflux in patients who have undergone proximal gastrectomy for early
      cancer of the gastric cardia.

PMID- 11957050
TI  - Obituary.

PMID- 11957049
TI  - Barrett's adenocarcinoma associated with acquired eventration of the diaphragm.
AB  - We report a rare case of Barrett's adenocarcinoma asso-ciated with acquired
      eventration of the diaphragm in a 71-year-old woman. She initially developed
      dysphagia and epigastric discomfort in May, 1997. On July 9, she was referred to
      our Department of Surgery at the Ryukyus University Hospital for thorough
      examination and treatment. Esophageal adenocarcinoma and eventration of the
      diaphragm were revealed by exhaustive examinations, including chest X-ray,
      computed tomography, and magnetic resonance imaging, and proximal gastrectomy
      with reconstruction of jejunal interposition was performed, on August 8.
      Histologically, the tumor revealed that the adenocarcinoma arose from short
      segment Barrett's esophagus (SSBE). It thus appears that eventration of the
      diaphragm may induce SSBE and Barrett's adenocarcinoma. We therefore recommend
      that periodic examinations of the esophagus and stomach be performed in patients
      with eventration of the diaphragm. Barrett's adenocarcinoma associated with
      acquired eventration of the diaphragm is reported. Patients with eventration of
      the diaphragm should undergo periodic examinations of the esophagus and stomach.

PMID- 11957051
TI  - Surgical quality control - A Herculean task not easily achieved The Dutch gastric
      trial as a primer.

PMID- 11957052
TI  - Inducement of canine gastric cancer by N-ethyl-N'-nitro-N-nitrosoguanidine
      (ENNG).
AB  - Achievements in the experimental inducement of canine gastric cancer in Japan are
      reviewed. Canine gastric cancer was initially induced experimentally by the
      administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water.
      However, intestinal sarcoma caused death before the gastric cancer was detected.
      By giving an N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)-soaked diet to dogs, we
      specifically induced gastric cancer and followed the process of carcinogenesis by
      X-ray, endoscopy, and biopsy. The initial macroscopic findings were areas of
      discoloration, with erosion or mucosal unevenness which became visible from
      approximately the 9th to 10th experimental months in mongrel dogs and around the
      13th to 17th months in beagle dogs. The protruded type of cancer occurred in
      mongrel dogs early in the experimental period, while the less protruded but more
      ulcerated gastric cancer occurred in beagle dogs later. Histological examination
      of the autopsied stomachs 277, 395, 546 and 813 day in mongreal dogs and 804,
      946, and 1591 day in beagle dogs revealed well differentiated, poorly
      differentiated, and undifferentiated adenocarcinoma. In animals with a lengthy
      survival (more than 600 days from the start of the experiment), metastases to
      lymph nodes, and, rarely, to liver, lung, bones, and other organs, were observed,
      as well as peritonitis carcinomatosa. Heterotransplantation of gastric cancer to
      nude mice succeeded to the fifth passage. Development of scirrhous cancer was
      induced in dogs by the combined use of ENNG and subcutaneous injection of
      gastrin, indicating that the experimentally induced canine gastric cancer
      resembled human gastric cancer. Although the induction of canine gastric cancer
      takes 2-3 years and the macroscopic type and time period differs among individual
      dogs, our results in the experimental induction of canine gastric cancer should
      be useful in various areas of research that require an animal model, such as
      genetic alteration during carcinogenesis, modulation of carcinogenesis, and
      prevention of gastric cancer.

PMID- 11957053
TI  - Epstein-Barr virus and gastric carcinoma.
AB  - Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), which accounts
      for most lymphoepithelioma-like gastric carcinoma and 10% or less of ordinary
      gastric carcinoma, is found worldwide and is the most common EBV-associated
      neoplasm. The pathologic features of EBVaGC are male predominance, occurrence
      primarily in the proximal stomach, multiplicity, moderately or poorly
      differentiated histological type, and association with lymphocytic infiltration.
      Virologically, EBV in EBVaGC is monoclonal or oligoclonal in the intramucosal or
      early invasive stage, and invariably monoclonal in advanced carcinomas. Latency
      type of gene expression in EBV is the same as that in Burkitt lymphoma (latency
      type I). Thus, EBVaGC is a unique type of gastric carcinoma, which is derived
      from a single or a few EBV-infected epithelial cells. However, there are still
      some unanswered questions, such as the mechanism of EBV infection of epithelial
      cells, the primary target in the gastric epithelium, the molecular events
      underlying EBVaGC, and the interaction of EBV with cytokine genes in cancer
      cells, as well as the predisposing factors for EBVaGC. To develop an experimental
      model, we recently established a transplantable EBVaGC - in severe combined
      immunodeficiency (SCID) mice - which retains the original EBV and the same
      pattern of latency gene expression as the original carcinoma. The development of
      a new therapeutic approach using this model, such as a gene therapy specific to
      EBV-associated neoplasm, will make EBVaGC not only a pathologically but also a
      clinically distinct gastric carcinoma entity.

PMID- 11957054
TI  - Incidence of nodal metastasis around the superior border of the pancreas based on
      number of metastatic perigastric nodes.
AB  - Lymph nodes along the superior border of the pancreas are not usually dissected
      in Western countries. The purpose of this study was to determine whether the
      number of metastatic perigastric nodes is predictive of supra-pancreatic nodal
      disease. Supra-pancreatic nodes are the nodes along the left gastric, common
      hepatic, celiac, or splenic arteries, including the splenic hilum. In 1230
      gastric carcinoma patients treated from 1985 through 1991 at the National Cancer
      Center Hospital, Tokyo, by D2 or more extensive dissection, 475 had nodal
      metastasis. Nodal involvement was limited to the perigastric nodes alone in 240
      patients, while supra-pancreatic node metastasis was observed in 235 patients. We
      examined the nodal status of supra-pancreatic nodes in relation to the number of
      metastatic perigastric nodes. When the number of metastatic perigastric nodes was
      3-6, 7-9, and 10 and more, the incidence of metastasis in nodes along the
      superior border of pancreas exceeded 30%, 50%, and 80%, respectively. When lymph
      nodes outside the perigastric area are not dissected, the likelihood of residual
      nodal disease can be predicted based on the number of involved perigastric lymph
      nodes. The 5-year survival rate in patients with supra-pancreatic node metastasis
      was high, at 39.2 % after systematic node dissection. If the number of
      perigastric metastatic nodes exceeds three, supra-pancreatic nodal dissection
      should be considered.

PMID- 11957055
TI  - Severe atrophic gastritis with Helicobacter pylori infection and gastric cancer.
AB  - BACKGROUND: We conducted a case-control study to evaluate whether patients with
      severe gastric atrophy (indicated by serum pepsinogen concentration) have a high
      risk of gastric cancer.METHODS: At the time of diagnosis of gastric cancer, sera
      from 301 patients (cases) and 602 sex- and age-matched cancer-free individuals
      (controls) were tested for the presence of anti- Helicobacter pylori IgG antibody
      (HM-CAP enzyme-linked immunoassay [ELISA] kit; Kyowa Medix, Tokyo, Japan) and
      serum pepsinogen (PG) levels (PG I and II Riabead Kits; Dainabot, Tokyo, Japan).
      We defined positivity for pepsinogen a pepsinogen I concentration of less than 70
      ng/mL and a PG I/II ratio of less than 3.0. We categorized the subjects according
      to serum pepsinogen levels and anti- Helicobacter pylori IgG antibody, creating
      four categories.RESULTS: Of the 301 cancer cases, 177 had positive serum
      pepsinogen levels, and 172 were positive for anti- Helicobacter pylori IgG
      antibody. The category in which subjects had positive serum pepsinogen levels and
      were negative for anti- Helicobacter pylori IgG antibody had the highest
      proportion (76.9%) of individuals with gastric cancer and the highest odds ratio
      (4.20) of the four categories. The odds ratios were 2.55 (95% confidence
      interval; 1.92-3.88) for positive serum pepsinogen levels and 0.93 (95%
      confidence interval; 0.63-1.27) for positive anti- Helicobacter pylori IgG
      antibody.CONCLUSION: These results suggest that patients with positive serum
      pepsinogen levels who are negative for IgG antibody to Helicobacter pylori,
      constitute a high-risk group for gastric cancer. Helicobacter pylori infection is
      associated with the development of gastric cancer by providing a suitable
      environment i.e., severe gastric atrophy, for carcinogenesis of the gastric
      mucosa.

PMID- 11957056
TI  - Clinicopathologic characteristics and prognostic factors in 10 783 patients with
      gastric cancer.
AB  - BACKGROUND: Although the results of gastric cancer treatment have markedly
      improved, this disease remains the most common cause of cancer death in
      Korea.METHODS: Clinicopathologic characteristics were analyzed for 10 783
      consecutive patients who underwent operation for gastric cancer at the Department
      of Surgery, Seoul National University Hospital, from 1970 to 1996. We also
      evaluated survival and prognostic factors for 9262 consecutive patients operated
      from 1981 to 1996. The clinicopathologic variables for evaluating prognostic
      values were classified as patient-, tumor-, and treatment-related factors. The
      prognostic significance of treatment modality [surgery alone, surgery +
      chemotherapy, surgery + immunotherapy + chemotherapy (immunochemosurgery)] was
      evaluated in patients with stage III gastric cancer (according to the
      International Union Against Cancer TNM classification of 1987). For the
      assessment of lymph node metastasis, both the number of involved lymph nodes and
      the ratio of involved to resected lymph nodes were analyzed, as a quantitative
      system.RESULTS: The mean age of the 10 783 patients was 53.5 years and the male
      to-female ratio was 2.07 : 1. Resection was performed in 9058 patients (84.0%
      resection rate). The 5-year survival rates were 55.9% for all patients and 64.8%
      for patients who received curative resection. Age, sex, preoperative hemoglobin
      and albumin levels, type of operation, curability of operation, tumor location,
      Borrmann type, tumor size, histologic differentiation, Lauren's classification,
      perineural invasion, lymphatic invasion, vascular invasion, depth of invasion,
      number of involved lymph nodes, ratio of involved to resected lymph nodes, and
      distant metastasis had prognostic significance on univariate analysis. Radical
      lymph node dissection, with more than 25 resected lymph nodes improved survival
      in patients with stage II and IIIa disease. As postoperative adjuvant therapy,
      immunochemotherapy was most effective in patients with stage III disease.
      Patients with identical numbers of lymph nodes -either the number of involved
      lymph nodes or the number of resected lymph nodes- were divided according to
      their ratios of involved-to-resected lymph nodes. In each numeric group, there
      were significant survival differences according to the ratio of involved-to
      resected lymph nodes. However, patients who had the same involved-to-resected
      lymph node ratio did not show significant differences in survival rate according
      to either the number of involved or the number of resected lymph nodes. On
      multivariate analysis, curability of operation, depth of invasion, and ratio of
      involved to resected lymph nodes were independent significant prognostic
      factors.CONCLUSIONS: Curative resection, depth of invasion, and lymph node
      metastasis were the most significant prognostic factors in gastric cancer. With
      regard to the status of lymph node metastasis, the ratio of involved to resected
      lymph nodes had a more precise and comprehensive prognostic value than only the
      number of involved or resected lymph nodes. Early detection and curative
      resection with radical lymph node dissection, followed by immunochemotherapy,
      particularly in patients with stage III gastric cancer should be the standard
      treatment in principle, for patients with gastric cancer.

PMID- 11957057
TI  - Phenotypic shift in human differentiated gastric cancers from gastric to
      intestinal epithelial cell type during disease progression.
AB  - BACKGROUND: The phenotypic expression of tumor cells is widely thought to
      resemble that of the tissue of origin. In the present study, to assess phenotypic
      changes that occur with disease progression, we investigated human differentiated
      gastric cancers at different depths of invasion for component cancer cell
      types.METHODS: Using a combined mucin histochemical and immunohistochemical
      approach, we classified surgical specimens of 301 differentiated gastric cancers
      into three types: gastric epithelial cell (G) type, intestinal epithelial cell
      (I) type and mixed gastric and intestinal (GI) type, according to the phenotypic
      differentiation of the component cancer cells. The relation between the
      phenotypic type of cancer and their depth of invasion was evaluated.RESULTS: The
      proportion of G type cancers was 41.4% in early (tumor invasion of mucosa or
      submucosa) cases, decreasing to 22.2% in advanced (tumor invasion of muscularis
      propia or deeper) cases, whereas the proportion of I type cancers increased with
      progressive disease from 23.5% to 31.1% ( P < 0.01). Cancers invading the
      subserosa or deeper included more I type cases and fewer G type than cancers
      limited to the mucosa ( P < 0.01). In most cases of each phenotypic type,
      intestinal metaplasia was recognized in the surrounding background mucosa, but no
      clear relation was shown between the phenotype of cancers and the degree of
      intestinal metaplasia in the background mucosa, suggesting that intestinal
      metaplasia is not always a preneoplastic lesion.CONCLUSIONS: A phenotypic shift
      from G to I type expression was observed with the progression of human
      differentiated gastric cancers. Intestinalization may occur independently in
      cancerous and noncancerous gastric mucosa.

PMID- 11957058
TI  - Matrix metalloproteinase 9 in mucosally invasive gastric cancer.
AB  - BACKGROUND: Matrix metalloproteinase 9 (MMP-9) facilitates tumor invasion and
      metastasis via basement membrane degradation. Control of MMP-9 production by
      cancer-stromal cell interactions in these processes has been observed.METHODS: We
      measured plasma MMP-9 concentrations, using a one-step sandwich enzyme
      immunoassay, and also immunohistochemically localized MMP-9 in patients with
      small gastric cancers limited to the mucosa. The cancers were classified as
      intraepithelial tumor (Tis) and T1 disease according to the tumor-node-metastasis
      (TNM) classification of the International Union Against Cancer.RESULTS: Patients
      with T1 disease had a higher positivity rate for and mean value of MMP-9 than
      patients with Tis disease. In T1 tumors, MMP-9 expression determined
      immunohistochemically, was greater in cells in cancer stroma than in cells in
      noncancerous stroma, a situation found in only a few Tis tumors.CONCLUSIONS:
      These results suggest that MMP-9 is related to the initial step of gastric cancer
      invasion.

PMID- 11957059
TI  - Nodal abdominal spread in adenocarcinoma of the cardia. Results of a multicenter
      prospective study.
AB  - BACKGROUND: Precise knowledge of the abdominal nodal spread of cardia
      adenocarcinoma in relation to the depth of invasion of the tumor and its
      longitudinal extension may be very important for the surgeon as a guide in
      choosing the type of resection and lymphadenectomy.METHODS: The frequency of node
      metastases in each abdominal station of the first and second tier was
      prospectively studied in 101 patients with type II and III cardia cancer (defined
      as approved by the consensus conference held during the second International
      Gastric Cancer Conference in Munich in April, 1997) who underwent total
      gastrectomy with D2 lymphadenectomy during the period January 1994 to April 1998.
      Lymph nodes were retrieved immediately after operation by the surgeon and
      assigned to the appropriate station according to the classification of the
      Japanese Research Society for Gastric Cancer.RESULTS: In early gastric cancer, of
      both type II and type III, lymph node involvement was limited to the perigastric
      nodes of the upper half of the stomach and to the lymph node station of the
      celiac trunk. In advanced cancers, whether of type II or type III, there was a
      fairly high frequency of metastases to the perigastric nodes of the lower half of
      the stomach; there was also high frequency of metastases at N2 stations, without
      differences in frequency between pT2 and pT3 tumors (staged according to the
      classification of the Japanese Research Society for Gastric Cancer).CONCLUSIONS:
      The results of our study provide evidence for the need to perform a total
      gastrectomy with D2 lymphadenectomy in all patients with advanced cardia cancer
      type II or type III. In early cancers, a less extensive resection (proximal
      gastrectomy) with D2 lymphadenectomy may be indicated.

PMID- 11957060
TI  - Quality control of lymph node dissection in the Dutch randomized trial of D1 and
      D2 lymph node dissection for gastric cancer.
AB  - BACKGROUND: Variability among surgeons and reduced protocol adherence threaten
      the conduct and outcome of surgical multicenter trials. We introduced, in the
      Dutch Gastric Cancer Trial of D1 and D2 (extended) lymph node dissection for
      gastric cancer, a novel way of managing instruction, quality control, and
      evaluation of protocol adherence.METHODS: Of 1078 patients entered in the Dutch
      trial, 711 patients with potentially curative resections were evaluated. Numbers
      and locations of lymph nodes detected at pathological investigation were compared
      according to the guidelines of the Japanese Research Society for the Study of
      Gastric Carcer. Non-compliance indicated inadequate removal of lymph node
      stations, whereas contamination indicated that lymph nodes were detected outside
      the intended level of dissection. Protocol adherence during the course of the
      trial, and the impact on complications, hospital mortality, and survival were
      evaluated.RESULTS: Major non-compliance was noted in 15.3% of D1 and 25.9% of D2
      patients. Contamination was present in 22.9% of D1 and 23.5% of D2 patients, and
      was limited to one or two lymph node stations only. Intensification of quality
      control resulted in only a marginal improvement in protocol adherence and in the
      number of lymph nodes detected. There was no association between protocol
      adherence and the occurrence of complications or long term survival.CONCLUSIONS:
      Contamination proved an important parameter to substantiate protocol adherence by
      the surgeon, whereas non-compliance had a multifactorial cause. Non-adherence to
      the protocol did not lead to increased hospital morbidity and mortality, but also
      had no impact on long term survival.

PMID- 11957061
TI  - Role of cyclin E and p53 expression in progression of early gastric cancer.
AB  - BACKGROUND: To elucidate the role that cyclin E overexpression plays in the
      progression of early gastric cancer, we examined the expression of cyclin E and
      p53, as abnormal p53 expression is linked with cyclin E overexpression in
      exerting adverse affects on the cell cycle.METHODS: Specimens from 108 early
      gastric cancers were stained by an immunohistochemical method, using anti-cyclin
      E and anti- p53 antibodies.RESULTS: The positivity rate of cyclin E expression in
      early gastric cancer was 33% (36/108). Cyclin E-positive tumors invaded more
      deeply ( P < 0.05), infiltrated lymphatic vessels more frequently ( P < 0.01),
      showed a higher incidence of differentiated cancer ( P < 0.01), and more often
      expressed p53 ( P < 0.01) than cyclin E-negative tumors. Differentiated cancers
      showing coexpression of cyclin E and p53 were more likely to metastasize to the
      lymph nodes.CONCLUSIONS: Overexpression of cyclin E may promote the progression
      of early gastric cancer.

PMID- 11957062
TI  - Gastric cancer: Today here, tomorrow where?

PMID- 11957063
TI  - Peritoneal and serum tumor markers predict recurrence and survival of patients
      with resectable gastric cancer.
AB  - BACKGROUND: Laparoscopy has become a useful adjunct for the staging of gastric
      cancer; yet, other than standard TNM staging, few additional variables can be
      used to predict survival. This study evaluated the utility of serum and
      peritoneal tumor markers (carcinoembryonic antigen [CEA] and carbohydrate antigen
      [CA]-125) as predictors of locoregional recurrence and distant disease-free
      survival in patients with gastric cancer.METHODS: During the period June 1990 to
      February 1994, 86 patients with gastric cancer were evaluated and deemed
      resectable by preoperative imaging studies. Serum levels of CEA and CA-125 were
      determined, and all patients underwent laparoscopic staging. Peritoneal washings
      were obtained from all patients, and 56 of these samples were evaluated for
      levels of CEA and CA-125.RESULTS: Sixteen (19%) of the 86 patients were found to
      have metastatic disease at laparoscopy; 67 of the remaining 70 patients underwent
      potentially curative gastrectomy. Serum CEA and CA-125 levels were predictive of
      survival in the entire group of patients. In patients who underwent curative
      gastrectomy, serum CEA predicted survival, whereas peritoneal CA-125 predicted
      peritoneal recurrence.CONCLUSIONS: Elevated serum levels of CEA and CA-125 are
      predictive of decreased survival in patients with gastric cancer. Furthermore,
      determination of peritoneal CA-125 helps to identify those patients at an
      increased risk for recurrent peritoneal disease.

PMID- 11957064
TI  - Analysis of immunoglobulin light-chain mRNA in gastric malignant lymphoma using
      new highly sensitive in situ hybridization method.
AB  - BACKGROUND: To analyze B-cell monoclonality, we need fresh materials for the
      Southern blotting method. In situ hybridization (ISH) for the detection of
      immunoglobulin light-chain mRNA can be used in formalin-fixed and paraffin
      embedded tissues. However, it is difficult to detect low levels of mRNA copies.
      So we must develop new highly sensitive in situ hybridization methods to diagnose
      gastric malignant lymphoma.METHODS: We analyzed materials from 15 patients with
      gastric malignant lymphoma, using a new highly sensitive ISH method, and compared
      the results with those of a conventional method.RESULTS: With this new method, 13
      of 15 cases were shown to have monotypic cytoplasmic signals, and monoclonality
      was detected in 3 of 4 cases of mucosa-associated lymphoid tissue (MALT)
      lymphoma.CONCLUSIONS: The accuracy of endoscopic biopsies is not satisfactory.
      However, the detection of immunoglobulin light chain mRNA, using the new highly
      sensitive ISH method with a non-radioactive isotope oligonucleotide probe, can be
      used to diagnose gastric malignant lymphoma even when conventional immunoglobulin
      light-chain mRNA or proteins alone cannot demonstrate the clonality.

PMID- 11957065
TI  - Advantages of Japanese response criteria for estimating the survival of patients
      with primary gastric cancer.
AB  - BACKGROUND: We conducted a retrospective study to investigate the adequacy of the
      Efficacy Criteria for Primary Lesions in the Japanese Classification of Gastric
      Cancer (Japanese criteria) for evaluating the anti-tumor efficacy of
      chemotherapies and the relationship between tumor regression and the prognosis of
      gastric cancer.METHODS: The data for 90 patients with inoperable ad-vanced
      gastric cancer who received various chemotherapies, consisting of fluorinated
      pyrimidines and cisplatin, were retrospectively analyzed. Based on the Japanese
      criteria, we investigated the efficacy of the chemotherapies and the relationship
      between the response in primary lesions and survival. We also compared the
      efficacy of chemotherapies evaluated by the Japanese criteria to that evaluated
      by the WHO criteria.RESULTS: All 90 patients were evaluable by the Japanese
      criteria. The overall response rate was 53.3% (Partial response [PR] in 48
      patients and no change + progressive disease [NC + PD] in 42 patients). The
      primary lesions were classified as measurable (a-lesions) in 27 patients,
      evaluable but not measurable (b-lesions) in 31 patients, and diffusely
      infiltrating (c-lesions) in 32 patients. Overall median survival time (MST) was
      9.4 months. The MSTs of the responders and non-responders were 12.6 and 7.8
      months, respectively. In contrast, by the WHO criteria, 49 patients (54.4%) were
      evaluable; the other 41 patients had gastric primary lesions alone but were not
      measurable by WHO criteria. The overall response rate was 67.3% (33/49), and
      overall MST was 9.4 months. The MSTs of the responders evaluated by both sets of
      criteria were both 12.6 months.CONCLUSIONS: We suggest that the Japanese criteria
      are useful for evaluating the anti-tumor effect of gastric cancer chemotherapies
      and that prospective studies to reconfirm their usefulness are warranted in
      Japan, and in Western countries.

PMID- 11957066
TI  - Suppression of T-cell function in gastric cancer patients after total gastrectomy
      with splenectomy: implications of splenic autotransplantation.
AB  - Background. In Japan since the 1960s, patients with gastric cancer have routinely
      had splenectomy combined with gastrectomy to ensure that lymph node dissection is
      complete. However, the influence of splenectomy on long-term immunity is
      unclear.METHODS: Forty-nine gastric cancer patients who underwent total
      gastrectomy for cure with ( n = 25) and without ( n = 24) splenectomy were
      assessed for immunologic function, including the proportion of lymphocyte
      subsets, purified protein derivative from tuberculin (PPD) response, natural
      killer (NK) activity, and phytohemagglutinin (PHA) response.RESULTS: Peripheral T
      cell mediated functions, e.g., PPD and PHA response, were significantly
      suppressed in patients who underwent gastrectomy with splenectomy compared with
      those who had gastrectomy alone. Decreased T-cell subsets (CD 3+, 4+, 8+) and
      increased NK cell subsets (CD 16+, 57+) were observed in patients who underwent
      splenectomy. Patients who did not undergo splenectomy had immunologic responses
      within the normal range.CONCLUSIONS: Splenectomy decreased T-cell mediated
      responses over the long term. As a potential means to co-rrect this T-cell
      dysfunction in patients with splenectomy, splenic autotransplantation should be
      considered in future research.

PMID- 11957067
TI  - Mast cell infiltration around gastric cancer cells correlates with tumor
      angiogenesis and metastasis.
AB  - BACKGROUND: Increased numbers of mast cells are found in various solid tumors. To
      investigate the role of mast cells in the vicinity of gastric cancer cells, we
      used special staining and an immunohistochemical technique.METHODS: Specimens
      were surgically obtained from 102 patients with gastric cancer. Mast cells around
      the tumor edge of gastric cancer nests were counted by staining with 0.05%
      toluidine blue solution. Blood vessels in these areas were also counted, by
      immunohistochemical staining of endothelial cells for factor VIII.RESULTS: The
      average number of mast cells and blood vessels in gastric cancer specimens was
      significantly higher than that in normal gastric tissue. Specimens from patients
      with advanced disease with metastases to lymph nodes had more mast cells than
      specimens from patients with early-stage disease. Mast cells in specimens from
      patients with metastatic lymph nodes were significantly increased in comparison
      with numbers in specimens from those without nodal metastases. Mast cell numbers
      in the specimens of patients with lymphatic or blood vessel invasion were
      significantly higher than numbers in specimens from patients without such
      invasion. Mast cells were localized near the new vessels around gastric cancer
      cells. Mast cell numbers increased as the number of blood vessels increased
      (correlation coefficient, 0.783). Postoperative survival curves revealed that
      patients with increased numbers of mast cells had a poor prognosis.CONCLUSIONS:
      All these results suggest that mast cell accumulation at the tumor site may lead
      to increased rates of tumor vascularization and, consequently, increased rates of
      tumor growth and metastasis.

PMID- 11957068
TI  - Risk factors for nodal micrometastasis of submucosal gastric carcinoma:
      assessment of indications for endoscopic treatment.
AB  - BACKGROUND: Despite the widespread use of endoscopic mucosal resection (EMR) for
      intramucosal gastric carcinoma, there is no standardized therapy for those
      patients in whom the carcinoma is found, after EMR, to have invaded the
      submucosa.Our aim in this study was to examine the relationship between the
      clinicopathological features of submucosal invasive carcinomas and their
      incidence of nodal micrometastasis, as detected by anti-human cytokeratin
      immunohistochemistry, in order to assess the curative potential of submucosal
      carcinoma by EMR.METHODS: Fifty surgically resected submucosal gastric carcinomas
      which would have satisfied the absolute indications for EMR, except for the
      criterion of submucosal invasion, were examined. The extent of submucosal
      invasion was determined by measuring its vertical and horizontal spread.
      Immunohistochemical analysis was performed with anti-human cytokeratin antibody
      (CAM5.2).RESULTS: Three of 50 cases (6.0%) were positive for nodal metastasis by
      routine H&E examination. Nodal micrometastases were detected in 11 of 47 cases
      (23.4%). Statistical analysis revealed that both the depth and the width of
      carcinoma in the submucosa were significantly larger in cases with than in those
      without micrometastasis ( P = 0.019 and P = 0.006, respectively). The group with
      lymphatic invasion showed more frequent micrometastasis than the group without (
      P = 0.014). There were no micrometastases in submucosal carcinomas whose
      submucosal invasion was less than 200 &mgr;m vertically and less than 320 &mgr;m
      horizontally.CONCLUSIONS: The present study indicates that differentiated gastric
      adenocarcinoma with minimal submucosal invasion (less than 200 &mgr;m vertically
      and less than 320 &mgr;m horizontally) and not accompanied by peptic ulcer or
      other risk factors, such as lymphatic invasion, can be considered as having high
      curative potential by EMR alone, without the necessity for further radical
      surgery.

PMID- 11957069
TI  - Surgical results of proximal gastrectomy for early-stage gastric cancer: jejunal
      interposition and gastric tube reconstruction.
AB  - BACKGROUND: The frequency of tumors in the upper one-third of the stomach has
      been increasing. The standard operation for proximal gastric cancer has been
      total or proximal gastrectomy. The aim of this study was to present the
      pathologic and surgical results of 30 patients with early-stage proximal gastric
      cancer managed by proximal gastrectomy.METHODS: A consecutive series of 30
      patients who underwent proximal gastrectomy for early-stage proximal gastric
      cancer was studied. Sixteen patients underwent jejunal interposition, while 14
      underwent gastric tube reconstruction, which consisted of a direct anastomosis
      between the esophagus and the remnant of the tube-like stomach.RESULTS: Twenty
      patients (67%) had no abdominal symptoms and the lesions were detected by
      screening gastric fiberscopy. The tumors were mostly located along the lesser
      curvature (73%), were grossly depressed type (IIc) (70%), and histologically well
      differentiated type (63%). The depth of wall invasion was the mucosa in 12
      patients, submucosa in 15, and muscularis propria in 3; lymph node metastasis was
      absent in 28 patients (93%). When compared with patients with jejunal
      interposition, patients with gastric tube reconstruction had a shorter operation
      time (327 vs 165 min), less blood loss (508 vs 151 g), and shorter hospital stay
      after operation (31 vs 17 days). Endoscopy and 24-h pH monitoring showed no
      evidence of reflux esophagitis, except in 1 patient with gastric tube
      reconstruction, and no patient died of recurrence.CONCLUSIONS: Early-stage
      proximal gastric cancer can be successfully treated by proximal gastrectomy.
      Since gastric tube reconstruction is a simple, easy, and safe procedure, proximal
      gastrectomy followed by gastric tube reconstruction is recommended for patients
      with early-stage proximal gastric cancer.

PMID- 11957070
TI  - Clinical significance of micrometastasis in bone marrow of patients with gastric
      cancer and its relation to angiogenesis.
AB  - BACKGROUND: Detection of micrometastasis is an important problem of clinical
      significance for a better understanding and control of tumor progression, which
      will improve patients' survival time.METHODS: To identify micrometastases in bone
      marrow, an immunocytochemical assay for epithelial cytokeratin protein was
      performed in 106 patients with primary gastric cancer. Also, in 40 of the 106
      patients, vascular endothelial growth factor (VEGF) expression and intratumoral
      vessel density were examined by an immunohistochemical staining method.RESULTS:
      Of the 106 patients, 22 (20.8%) presented with cytokeratin-positive cells in bone
      marrow at the time of primary surgery. The positive findings were related to
      depth of invasion, peritoneal dissemination, and liver metastasis. Patients with
      cytokeratin-positivity in bone marrow had a higher VEGF positive rate (73%; 8/11)
      than did cytokeratin-negative patients (48%; 14/29). Intratumoral vessel density
      in VEGF-positive patients was 26.9 +/- 10.3, which was significantly higher than
      that in VEGF-negative patients (13.2 +/- 8.7, P < 0.05). Thus, the presence of
      cytokeratin-positive cells in bone marrow was closely related to angiogenesis in
      the primary tumor.CONCLUSIONS: Cytokeratin staining can be useful for identifying
      patients at high risk for metastasis. Prophylactic lymph node dissection,
      adjuvant chemotherapy, and antiangiogenic treatment may be necessary for patients
      with micrometastasis.

PMID- 11957071
TI  - Treatment of peritoneal dissemination of gastric cancer with sequential
      methotrexate and 5-fluorouracil.
AB  - BACKGROUND: Pretreatment with methotrexate (MTX) followed by 5-fluorouracil (5
      FU) (sequential MTX and 5-FU), exerts biochemical modulation in which the
      antitumor effect of 5-FU is enhanced by the preceding MTX. Since the early 1980s,
      the sequential MTX/5-FU regimen has been employed clinically for gastric cancer
      in Japan, with high response rates for undifferentiated type gastric
      carcinoma.METHODS: Peritoneal dissemination is more frequent in undifferentiated
      type carcinoma, we therefore employed sequential MTX and 5-FU for the treatment
      of 39 gastric cancer patients with peritoneal dissemination. We also investigated
      MTX levels in blood and ascitic fluid during the treatment.RESULTS: Partial
      response (PR) was achieved in 6 of 26 patients (23%) who had evaluable lesions.
      PR lesions included abdominal wall tumors, primary gastric foci, inguinal lymph
      node, and rectal stenosis. Ascites was eliminated in 50% of the patients, and
      pleural effusion disappeared in 2 patients.CONCLUSIONS: In our study, sequential
      MTX and 5-FU had low toxicity and was beneficial for advanced gastric cancer
      patients with peritoneal dissemination. Further investigation of this treatment
      as induction and postoperative adjuvant chemotherapy for Borrmann type 4 gastric
      cancer seems warranted.

PMID- 11957072
TI  - Neoadjuvant chemotherapy in advanced gastric cancer with non-curative factors: a
      Phase II study with 5-fluorouracil, leucovorin, and cisplatin.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) has recently received increasing
      attention in an attempt to increase the rate of complete tumor resections, reduce
      systemic metastases, and prolong survival in patients with advanced gastric
      cancer.METHODS: Since 1993, 21 patients with unresectable or non-curative
      resectable gastric cancer received NAC, consisting of 5-fluorouracil, leucovorin,
      and cisplatin (FLP) with at least two cycles before surgery.RESULTS: All except 2
      patients underwent surgical treatment, and resection was performed in 18 (85.7%).
      There were no deaths and no major morbidity following operation. There was no
      complete response (CR), but 12 patients (57.1%) had a partial response (PR), the
      response rate was 47.6% for the primary region, 64.7% for abdominal para-aortic
      (No.16) lymph node metastasis, 40.0% for liver metastasis, and 11.1% for
      peritoneal dissemination. One-year survival of the 21 patients was 40.5%, and
      median survival time (MST) was 322 days. MST in the responders was 571 days, and
      that in non-responders was 199 days ( P < 0.01). MST was 835 days in patients who
      underwent curative resection and 310 days in those who underwent non-curative
      surgery ( P < 0.01). There was no grade 4 toxicity, but grade 3 leukopenia
      occurred in 4 patients (19.0%), grade 3 anemia occurred in 3 patients (14.3%),
      and grade 3 stomatitis in 2 patients (9.5%). There were no serious renal
      disorders and no treatment-related death.CONCLUSIONS: The combination of FLP for
      NAC was feasible and useful for tumor reduction, especially for No.16 lymph node
      metastasis. There was a survival benefit in patients whose tumor had PR or who
      had had curative resection. We should confirm the effect and survival benefit of
      FLP for NAC by a prospectively randomized clinical controlled study.

PMID- 11957073
TI  - Oral UFT (uracil plus futrafur) for neoadjuvant chemotherapy of gastric cancer.
AB  - BACKGROUND: Neoadjuvant chemotherapy has become one of the topics of interest in
      chemotherapy of gastric cancer; the present study assessed the clinical benefits
      of neoadjuvant chemotherapy with oral uracil and futrafur (UFT) for gastric
      cancer.METHODS: Between 1991 and 1997, 82 patients with gastric cancer (36 with
      early and 46 with advanced cancers) received UFT at 300-600 mg/day orally for 1-6
      weeks before surgery. Objective responses, histological effects, and postsurgical
      survival rates were assessed.RESULTS: In 69 of the 82 patients, the objective
      responses of the primary lesions were assessed by endoscopy or upper
      gastrointestinal series examination, and 2 complete responses (CR)s, 25 partial
      responses (PRs), and 42 no changes (NCs) were seen (39.1% response). Histological
      effects were evaluated in 82 patients, and 2 grade 3, 11 grade 2, 11 grade 1b, 27
      grade 1a, and 31 grade 0 effects were seen. A longer period of UFT administration
      was associated with a CR or PR. However, the objective responses did not
      correlate with the histological effects. All the patients underwent gastrectomy,
      and during the median follow-up period of 41 months, 3-year survival rates were
      97.1% for pTNM stage 1, 75% for stage 2, 86.7% for stage 3, and 41.6% for stage
      4. The survival rates of stage 3 and stage 4 patients were higher than those of
      the historical controls in our department. However, CR or PR did not correlate
      with the improvement in survival. Side effects before surgery were not serious;
      they included slight myelotoxicity, liver dysfunction, and anorexia; however, 3
      patients (3.7%) had suture insufficiency, 3 patients (3.7%) had methicillin
      resistant Staphylococcus aureus (MRSA) enteritis, and 7 patients (8.5%) had liver
      dysfunction.CONCLUSIONS: Preoperative chemotherapy for gastric cancer with oral
      UFT was safe and resulted in a good local response (macro- and microscopically)
      which may indicate the possibility of improved survival with neoadjuvant
      chemotherapy with UFT. Furthermore, preoperative chemotherapy with oral UFT is
      easy and patients can receive this treatment on an outpatient basis.

PMID- 11957074
TI  - Risk of second malignancies after surgical treatment for early gastric cancer.
AB  - We evaluated the follow-up of 105 patients who received surgical treatment at our
      Institute for early gastric cancer (EGC). Median follow-up was 71 months.
      Operative mortality was 5.7% and the 5-year survival rate was 82.8%,
      approximately that of an age- and sex- matched Italian population. Overall
      mortality was assessed with regard to mortality from gastric cancer or other
      causes. Ten second primary malignancies were identified, and the standardized
      mortality ratio (1.12; 90% confidence interval [CI] 0.77-1.64) and standardized
      morbidity ratio (1.50; 90% CI 0.89-2.50) were determined using data from the
      Tumor Registry of Lombardy. To our knowledge, this is the biggest Western series
      to measure the risk EGC patients face of developing a second primary tumor. In
      conclusion, oncologists who follow-up patients surgically treated for EGC, a
      disease that is much less frequent in Western countries than in Eastern ones,
      should be aware of the possible occurrence of extragastric primary tumors so that
      they may plan the appropriate diagnostic investigation when necessary.

PMID- 11957075
TI  - Gastric cancer presenting with obstructive jaundice.
AB  - Gastric cancer is rarely associated with obstructive jaundice, which is
      associated with poor survival. We describe five patients with gastric cancer who
      presented with jaundice. Two patients had primary gastric cancer and three had
      recurrent disease. The patients were treated by operation, chemotherapy, and
      percutaneous transhepatic biliary drainage (PTBD) according to the stage of the
      cancers. Although these treatments often fail to prolong survival, chemotherapy
      and PTBD can improve patient's quality of life.

PMID- 11957076
TI  - The second English edition of the Japanese Classification of Gastric Carcinoma. A
      Western commentary.

PMID- 11957077
TI  - Reply to Professor Hermanek's comments on the new Japanese classification of
      gastric carcinoma.

PMID- 11957078
TI  - Adenocarcinoma of the esophago-gastric junction.

PMID- 11957079
TI  - Results of surgical therapy in patients with adenocarcinoma of the esophagus and
      cardia.
AB  - BACKGROUND: Adenocarcinoma of the esophagus and cardia is a challenging disease
      for the surgeon. Delay in diagnosis, nodal involvement, and incompleteness of
      resection have an adverse effect on long-term prognosis. Efforts are currently
      oriented to identify patients who may benefit from extensive resection.METHODS:
      Between November 1992 and May 1998, 218 patients with histologically proven
      adenocarcinoma of the distal esophagus or cardia were referred to our Department.
      In 6 patients (10.2%) cancer was discovered during endoscopic surveillance for
      Barrett's metaplasia. Overall, 147 patients (67%) underwent resection. An Ivor
      Lewis approach was used in 121 patients; of these, 51 underwent an extended
      mediastinal lymph node dissection.RESULTS: Median cumulative survival was 25.9 +/
      3.1 months in patients undergoing resection, and 7 +/- 1.3 months in patients
      having palliation ( P < 0.01). Survival was significantly higher in patients with
      negative nodes than in those with lymph node metastases (54 +/- 12.9 versus 17 +/
      2.8 months; P < 0.01). Six of the 51 patients (11.8%) undergoing extended lym
      phadenectomy had metastatic upper mediastinal nodes. Additional serial sections
      and immunohistochemistry were performed in 46 patients. In 6 of 18 patients
      (33.3%) with negative nodes at conventional hematoxylin-eosin examination,
      immunohistochemistry demonstrated micrometastases in the lesser curvature,
      paracardial, peripancreatic, or lower mediastinal nodes. Three of these patients
      had recurrent disease within the first year of follow-up.CONCLUSIONS: Early
      diagnosis remains the prerequisite for curative treatment of adenocarcinoma of
      the esophagus and cardia. Endoscopic surveillance appears to be warranted in
      patients with Barrett's metaplasia. When a curative resection is attempted,
      extended lymphadenectomy improves tumor staging and may prevent local
      recurrences. Serial sections and immunohistochemistry provide additional accuracy
      in the staging of the disease and may prove useful to select patients for
      adjuvant therapy.

PMID- 11957080
TI  - Clinicopathological value of immunohistochemical detection of occult involvement
      in pT3N0 gastric cancer.
AB  - BACKGROUND: In cases of pT3 gastric cancer, even when standard histological
      staining reveals no evidence of metastases in the regional lymph nodes, patients
      still may die of postoperative recurrence of the tumor. An attempt was made in
      the present study to explain the unfavorable outcome of such patients by
      investigating the presence of occult cancer cells in lymph nodes by
      immunostaining of cytokeratin.METHODS: We examined 2310 lymph nodes that had been
      removed from 83 patients with stage II gastric cancer (pT3, N0, M0). Two
      consecutive sections of 4 &mgr;m thick were prepared for simultaneous staining
      with hematoxylin and eosin and immunostaining with the CAM 5.2 monoclonal
      antibody against cytokeratin, respectively.RESULTS: Evidence of occult
      involvement was found in 299 of 2310 (13%) lymph nodes and in 54 of 83 (65%)
      patients with pT3 gastric cancer. An analysis of survival demonstrated the
      limited 5-year survival of patients with occult involvement in their resected
      lymph nodes, as compared with that of patients without involvement ( P < 0.01).
      Moreover, the patients in whom group 2 lymph nodes had occult cancer cells had a
      significantly poorer prognosis than those in whom occult involvement was limited
      to group 1 lymph nodes ( P < 0.05).CONCLUSIONS: The accuracy of predictions of
      prognosis of patients with pT3 gastric cancer should be greatly enhanced if
      cytokeratin-specific immunostaining is performed in conjunction with routine
      histopathological examination of lymph nodes.

PMID- 11957081
TI  - Atrophic gastritis, Epstein-Barr virus infection, and Epstein-Barr virus
      associated gastric carcinoma.
AB  - BACKGROUND: The developmental process of Epstein-Barr virus (EBV)-associated
      gastric carcinoma (EBVaGC) has not been clearly demonstrated, especially in its
      relation to intestinal metaplasia and epithelial EBV infection.METHODS: Gastritis
      and intestinal metaplasia was histologically evaluated in non-neoplastic gastric
      mucosa that surrounded early carcinoma of EBVaGCs ( n = 23) and EBV-negative
      gastric carcinomas (GCs) (intestinal type, n = 139; diffuse type, n = 44).
      Helicobacter pylori infection was evaluated by immunohistochemistry. EBV
      infection in the gastric mucosa was examined by both RNA probe in situ
      hybridization (ISH) and polymerase chain reaction (PCR) for the BamHI-W region of
      EBV DNA, the latter of which was applied to the microdissected mucosa.RESULTS:
      Marked grade of atrophy and moderate to marked grade of lymphocytic infiltration
      were significantly more frequent in EBVaGCs (74% and 78%, respectively), compared
      to intestinal-type (49% and 12%)and diffuse-type (27% and 12%) of EBV-negative
      GCs. Only 13% of EBVaGCs were surrounded by intestinal metaplasia, in contrast to
      41% of intestinal-type EBV-negative GCs. Immunohistochemistry revealed nearly the
      same frequencies of H. pylori infection (70%) in three types of GCs. RNA probe
      ISH for EBV-DNA failed to identify any positive cells in nonneoplastic mucosa,
      including intestinal metaplasia. Two of 118 microdissected samples of EBVaGC and
      5 of 62 samples of EBV-negative GCs showed amplification of EBV-DNA, consisting
      of 3 pyloric and 4 fundic but no metaplastic gland samples.CONCLUSIONS: EBVaGC
      may develop from rare EBV-infected epithelial cells with severe atrophic
      gastritis, but the process is not directly related to intestinal metaplasia or H.
      pylori infection.

PMID- 11957082
TI  - Laparoscopy in the management of scirrhous gastric cancer.
AB  - BACKGROUND: Scirrhous gastric cancer frequently shows extensive tumor spread, and
      gastrectomy for cure of the disease is not possible in the presence of peritoneal
      dissemination, which is often overlooked by conventional computed tomography. The
      aim of this study was to evaluate our experience of 16 patients who underwent
      laparoscopy in the management of scirrhous gastric cancer, and to examine whether
      peritoneal dissemination could be diagnosed accurately by laparoscopy.METHODS:
      All patients had nonobstructed, nonbleeding scirrhous gastric cancer and had no
      evidence of metastatic disease by ultrasonography and computed tomography.
      Laparoscopy was performed under general anesthesia with CO(2) pneumoperitoneum. A
      Hasson trocar and two manipulating forceps were inserted, and the surfaces of the
      peritoneum, omentum, stomach, spleen, pancreas, liver, and diaphragm were
      examined.RESULTS: The mean time for laparoscopy was 20 min. Peritoneal
      dissemination was disclosed in 4 patients (25%), and systemic and intraperitoneal
      chemotherapy was done without laparotomy. In 12 patients, subsequent gastrectomy
      with a curative intent was successfully performed. Pathology revealed that the
      tumor diffusely invaded the whole thickness of the gastric wall; the mean size of
      resected tumors was 12 cm, and the mean number of positive nodes was 17. Nine
      patients died of the disease with a mean survival period of 10 months, and 7
      patients were alive without recurrence during a mean follow-up period of 11
      months.CONCLUSIONS: Laparoscopy is useful for the evaluation of peritoneal
      spreads of advanced gastric cancer, can avoid unnecessary laparotomy because of
      peritoneal dissemination, and is important for the choice of treatments in
      patients with scirrhous gastric cancer.

PMID- 11957083
TI  - Long-term results of early gastric cancer accomplished in a European institution
      by Japanese-type radical resection.
AB  - BACKGROUND: Long-term survival following Japanese-type radical surgery for 130
      consecutively performed early gastric cancers (EGC) in a single Austrian
      institution between January 1, 1984 and May 31, 1998 was analyzed in terms of
      long-term survival, postoperative morbidity, and mortality.METHODS: Extended D2
      lymphadenectomy as defined by the JRSGC was performed in 129 patients with EGC.
      The surgical process was consistent as nearly all patients were operated on by
      only two surgeons. Overall survival and factors influencing survival were
      analyzed with particular regard to the depth of tumor infiltration, histological
      type, tumor grading, Lauren classification, tumor diameter, macroscopic
      appearance, localization, and lymph node involvement.RESULTS: Of 678 gastric
      cancer patients surgically treated in the mentioned period, 130 patients (19.2%)
      were qualified as EGC. In 70 patients the tumor was limited to the mucosa and in
      60 patients the tumor had not yet invaded the submucosa. The percentage of
      patients with positive lymph nodes increased from 2.9% with mucosal invasion to
      21.7% with submucosal tumor involvement. The overall 5- and 10-year observed
      survival rate, postoperative mortality not excluded, was 74.6% and 62.1%,
      respectively, and 91.1% and 91.1%, respectively, when calculated as tumor
      specific. The 5- and 10-year observed survival rate of tumors limited to the
      mucosa was 77.2% and 72.1%, respectively, and 98.1% and 98.1%, respectively, when
      calculated as tumor specific. The respective values for submucosal invasion were
      71.6% and 51.7%, and 82.7% and 82.7%. Postoperative complications occurred in 17
      patients (13.1%) and postoperative hospital mortality totaled 1.5% (2/130). In
      multivariate analysis, only lymph node metastases were found to have independent
      prognostic influence on survival ( P < 0.001; hazard ratio, 8.25).CONCLUSION:
      Japanese-type radical lymph node dissection for EGC in a European surgical
      institution yielded long-term survival nearly identical to that reported
      repeatedly by Japanese authors. Postoperative morbidity and mortality was not
      sacrificed by our comparatively radical surgical approach.

PMID- 11957084
TI  - Evaluation of the ratio of lymph node metastasis as a prognostic factor in
      patients with gastric cancer.
AB  - BACKGROUND: Lymph node metastasis in patients with gastric cancer is one of the
      important prognostic factors. However, there is no consensus concerning the best
      classification for lymph node metastasis as a prognostic factor. So, to evaluate
      the ratio of the number of metastatic lymph nodes to the total number of
      dissected lymph nodes (the ratio of LN meta) as a prognostic factor, we compared
      the ratio of LN meta with lymph node status according to the Japan Classification
      of Gastric Carcinoma and the total number of metastatic lymph nodes with
      multivariate analysis.METHODS: Between 1991 and 1997, a total of 360 patients
      with primary gastric cancer who underwent gastrectomy with D2 or more extended
      lymph node dissection were included in this study. Ten kinds of prognostic
      factors and three types of different classifications for lymph node metastasis
      were analyzed by multivariate analysis using the Cox regression.RESULTS: The
      average number of dissected lymph nodes and metastatic lymph nodes were 55.0
      (range, 11-184) and 2.6 (range, 0-86), respectively. There were significant
      differences of the 5-year cumulative survival rates among each group of the ratio
      of LN meta (0%, 1%-9%, 10%-24%, and more than 25%). Age, tumor size, curability,
      and the ratio of LN meta were selected as independent prognostic factors by
      forward stepwise selection. The ratio of LN meta showed the highest hazard ratio
      by Cox regression.CONCLUSION: The ratio of LN meta appears to be an important
      prognostic factor and the best classification factor for lymph node metastasis.

PMID- 11957085
TI  - Clinicopathological features of the superficial spreading type of early gastric
      cancer.
AB  - BACKGROUND: During a 10-year period (1986-1995), 59 of 538 patients with early
      gastric cancer (11.0%) had the superficial spreading type of gastric cancer. We
      attempted to elucidate the clinicopathological features and investigated the
      influence of those features on surgical procedures and patient prognoses.METHODS:
      These 59 superficial spreading lesions were analyzed with respect to macroscopic
      type, lymph node (LN) metastasis, recurrent pattern, and method of surgical
      operation. In addition, the lesions were compared with those of 393 other
      patients with small-sized cancer.RESULTS: In both groups, the IIc type
      macroscopic lesion occurred most frequently, and the depressed subtype occurred
      more frequently than the elevated subtype. There was no significant histologic
      difference between the groups. The incidence of LN metastasis was 8.7% in early
      gastric cancer, 7.1% in small-sized cancer, and 20.3% in superficial spreading
      cancer. The incidence of lymphovascular invasion was 24.4% in small-sized cancer
      and 50.8% in superficial spreading cancer. The incidences of LN metastasis and
      lymphovascular invasion were greater in superficial spreading cancer than in
      small-sized cancer. Despite extensive preoperative examination, determination of
      the tumor margin was impossible in 26 of the 59 patients with superficial
      spreading cancer. The incidence of recurrence was 2.0% in small-sized cancer and
      5.1% in superficial spreading cancer.CONCLUSIONS: A wide resection with extensive
      lymph node dissection (D2 or more) seems to be an appropriate treatment for the
      superficial spreading type of early gastric cancer.

PMID- 11957086
TI  - Primary squamous cell carcinoma of the stomach.
AB  - Primary squamous cell carcinoma (SCC) of the stomach is extremely rare; only 32
      cases are found in the Japanese literature. The pathogenesis of this neoplasm
      remains obscure and controversial. Furthermore, the optimal treatment, including
      adjuvant chemotherapy, remains unclear. We report herein a case of SCC of the
      stomach in a 70-year-old male with amazing effectiveness of neoadjuvant
      chemotherapy, low-dose FP chemotherapy. To our knowledge, no case of this disease
      has ever been reported that was given neoadjuvant chemotherapy and histologically
      showed its effectiveness. Our case demonstrated a striking effectiveness of
      chemotherapy in the neoplasm both radiologically and histologically.

PMID- 11957087
TI  - A long surviving case of resected gastric cancer presenting with a synchronous
      adrenal metastasis.
AB  - Clinically curable adrenal metastases are rare. We treated a patient with gastric
      cancer and a synchronous adrenal metastasis who underwent curative resection.
      Upper GI examinations of a 75-year-old man revealed a Borrmann 3 gastric tumor in
      the proximal stomach. CT indicated a giant gastric tumor that invaded the
      pancreatic tail, and the left adrenal gland seemed normal. He was subjected to a
      total gastrectomy and a distal pancreatosplenectomy. Because a mass was palpated
      intraoperatively in the left adrenal gland, it was also removed. The gastric
      tumor was histopathologically a poorly differentiated adenocarcinoma with
      scirrhous invasion that invaded the pancreas, and the histopathological findings
      of the left adrenal tumor were compatible with those of gastric cancer. At
      present, 6 years after the operation, there has been no clear sign of cancer
      recurrence. It may be rational to excise the left adrenal gland en bloc in
      patients with serosa-positive Borrmann 3-4 gastric cancer.

PMID- 11957088
TI  - Meeting report of the 71st Japanese Gastric Cancer Congress.

PMID- 11957089
TI  - State of the art in the treatment of gastric cancer: from the 71st Japanese
      Gastric Cancer Congress.
AB  - The recent literatures has few reports of the state of the art and latest results
      in the treatment of gastric cancer, although such information is necessary for
      conducting new clinical trials and for obtaining informed consent from patients.
      In the panel discussions at the 71st Gastric Cancer Congress of Japan (held in
      Tokyo, June 1999), 18 representative institutions and hospitals in Japan reported
      their latest results for the surgical treatment of gastric cancer, indicating the
      state of the art in the treatment of gastric cancer. Here we report a summary of
      these sessions.

PMID- 11957090
TI  - Genotypes of glutathione S-transferase M1 and N-acetyltransferase 2 in Japanese
      patients with gastric cancer.
AB  - BACKGROUND: Genetic polymorphisms of some metabolizing enzymes, such as
      glutathione S-transferase M1 ( GSTM1) and N-acetyltransferase 2 ( NAT2), have
      recently been shown to affect individual susceptibility to various types of
      cancers. However, the link between the GSTM1 polymorphism and gastric cancer is
      controversial and there are few studies focusing on the relation between a
      combination of the two enzyme genotypes and gastric cancer risk.METHODS:
      Genotypes of GSTM1 and NAT2 were determined by polymerase chain reaction (PCR) or
      restriction fragment length polymorphism (RFLP) following PCR in 147 Japanese
      patients with gastric cancer and 112 autopsied Japanese patients without stomach,
      lung, urinary bladder, or colon cancer.RESULTS: The frequency of the GSTM1 null
      genotype was significantly increased in the cancer patients (91 individuals;
      61.9%) compared with the controls (55 individuals; 49.1%) ( P < 0.05; odds ratio,
      1.68). The incidence of patients with the homozygously wild genotype of NAT2
      (rapid acetylator) was slightly lower in the cancer group (59 individuals; 40.1%)
      than in the control group (58 individuals; 51.8%). The proportion of patients
      with both the GSTM1 gene and homozygously wild genotype of NAT2 was significantly
      smaller in the cancer group (19 individuals; 12.9%) than in the control group (29
      individuals; 25.9%) ( P < 0.05). In addition, in a comparison of four subgroups
      of gastric cancer which were classified by both the genotype of GSTM1 and the
      predicted phenotype of NAT2, the number of subjects in the subgroup "
      GSTM1+/rapid" was significantly smaller than the expected numbers of the other
      three subgroups ( P < 0.05).CONCLUSION: It is suggested that a combination of
      GSTM1 and NAT2 decreases the risk of gastric cancer in Japanese patients.

PMID- 11957091
TI  - Expression of thymidylate synthase and thymidine phosphorylase in recurrence and
      survival rates of advanced gastric cancer.
AB  - BACKGROUND: The immunohistochemical expression of thymidylate synthase (TS) and
      thymidine phosphorylase (TP) was examined in a comparative study of the
      recurrence rates and prognoses of patients with advanced gastric cancer at the
      same stage.METHODS: We examined the resected specimens of 67 patients with stage
      IIIB gastric cancer (pT3, pN2, M0) under 70 years of age who had undergone
      curative gastrectomy followed by adjuvant chemotherapy with 5-fluoropyrimidines.
      Paraffin sections of the resected specimens were stained with human anti-TS
      polyclonal and anti-TP monoclonal antibodies by the avidin-biotin-peroxidase
      complex (ABC) method.RESULTS: The overall expression of TS and TP was 45.4% and
      43.4%, respectively. The postoperative survival curve for the TS-positive group
      was significantly depressed compared with that for the TS-negative group ( P =
      0.0480). The survival curves for TP-positive and TP-negative groups did not show
      any difference. In regard to the combination of TS and TP expression, the best
      survival curve was obtained for the TS(-)/TP(+) group, followed by those for the
      TS(-)/TP(-), TS(+)/TP(-), and TS(+)/TP(+) groups in descending order. With regard
      to the recurrence site, there was no significant difference in peritoneal
      recurrence in relation to positivity for TS or TP. Lymph node recurrence,
      however, was significantly higher in the TS-positive and TP-positive groups, with
      P-values being 0.0466 and 0.0058, respectively, versus the corresponding negative
      groups. The incidence of hepatic recurrence was higher in the TP-positive group
      than in the TP-negative group ( P = 0.0910). As for the total doses of 5
      fluoropyrimidines given, more favorable survival curves were obtained for the
      high dose of negative TS and TP groups, but no significant differences were
      observed in their positivities.CONCLUSION: The expressions of TS and TP showed
      different characteristics in overall survival and recurrence rate or site. They
      should be used for predicting prognosis in comprehension on their properties.

PMID- 11957092
TI  - Immunohistochemical detection of lymph node microinvolvement in node-negative
      gastric cancer.
AB  - BACKGROUND: Despite curative resection of the primary tumor with extensive
      dissection of lymph nodes, some patients with node-negative gastric cancer die of
      local relapse or metastatic disease. Microinvolvement of regional lymph nodes may
      play an important role in the prognosis.METHODS: To evaluate the incidence and
      prognostic implications of regional lymph node microinvolvement in node-negative
      gastric cancer, we retrospectively analyzed tissue samples from 51 patients
      operated on for primary gastric cancer. They had tumors that invaded beyond the
      muscularis propria, but without metastasis to the lymph nodes, shown by the
      conventional H&E staining method. The regional lymph nodes were examined
      immunohistochemically, using monoclonal antibodies against cytokeratin.RESULTS:
      Microinvolvement was found in 4.8% of lymph nodes (67/1390) and in 43.2% of the
      patients (22/51). The clinical outcome of the patients with microinvolvement was
      not significantly different from those without it. However, no patient died in
      the no-microinvolvement group, while three patients in the microinvolvement group
      died of recurrence.CONCLUSION: The incidence of microinvolvement in
      conventionally negative lymph nodes cannot be ignored, and detecting
      microinvolvement may be important for predicting recurrence of gastric cancer.

PMID- 11957093
TI  - Paraaortic lymph node micrometastasis and tumor cell microinvolvement in advanced
      gastric carcinoma.
AB  - BACKGROUND: Paraaortic lymph node dissection in advanced gastric carcinoma is
      controversial. The purpose of this study was to investigate the incidence and
      significance of micrometastasis (MM) or tumor cell microinvolvement (TCM) in
      these critical lymph nodes.METHODS: A total of 2339 lymph nodes, including 390
      paraaortic nodes, obtained from 47 patients with advanced gastric carcinoma were
      examined immunohistochemically, using cytokeratin antibody.RESULTS: Lymph node
      metastasis was found in 95 of the 390 paraaortic nodes of 14 patients by routine
      histological examination. MM or TCM was immunohistochemically detected in 45 of
      the 295 negative paraaortic lymph nodes from 15 of 33 patients (MM, n = 5; TCM, n
      = 10). The 5-year-survival rate in the paraaortic node-negative group and
      cytokeratin-positive group was significantly higher that that of the hematoxilin
      and eosin-positive group. The total number of lymph node metastases by
      hematoxylin and eosin staining and the pathological lymph node compartments, by
      cytokeratin-positive nodes, were prognostic factors by multivariate
      analysis.CONCLUSIONS: We demonstrated a high rate of MM or TCM in the paraaortic
      lymph nodes and suggest that such harbored metastases are related to the
      prognosis of patients with advanced gastric carcinoma. On the basis of this
      study, a multi-institutional study should be considered.

PMID- 11957094
TI  - Completely laparoscopic extraperigastric lymph node dissection for gastric
      malignancies located in the middle or lower third of the stomach.
AB  - Dissection of the extraperigastric lymph nodes is necessary in most submucosal
      gastric cancers. Laparoscopy-assisted gastrectomy with extraperigastric lymph
      node dissection via minilaparotomy has been performed, but, to our knowledge,
      completely laparoscopic extraperigastric lymph node dissection has never been
      reported. We successfully performed completely laparoscopic distal gastrectomy
      with extraperigastric lymph node dissection in 12 patients, of whom 11 had early
      gastric cancer and 1 had malignant lymphoma. This surgery is technically
      feasible, has an acceptable complication rate, and a curability similar to that
      with open surgery.

PMID- 11957096
TI  - Suture line recurrence in jejunal pouch replaced after total gastrectomy for
      gastric cancer.
AB  - We report a case of suture line recurrence in a jejunal pouch, diagnosed 4 months
      after total gastrectomy for advanced gastric cancer. The jejunal pouch was made
      with a linear stapler, without intraluminal irrigation being carried out before
      anastomosis, and was replaced in an interposition fashion. We propose that the
      recurrence was caused by the implantation of exfoliated cancer cells in either
      the intraluminal mucus or on a contaminated stapling device.

PMID- 11957095
TI  - Gastric carcinoma resembling submucosal tumor.
AB  - Acase of stomach carcinoma showing features of submucosal tumor is reported. The
      patient was a 50-year-old man presenting with hematemesis. Endoscopic examination
      was performed and revealed a submucosal tumor-like lesion with central ulceration
      in the fornix of the stomach. The biopsy specimen from this lesion showed poorly
      differentiated adenocarcinoma, and surgery was performed. The tumor, measuring
      3.5 x 2.7 cm in size, invaded to the muscularis propria with proliferation of the
      interstitial connective tissue and lymphoid follicles consisting mainly of B
      lymphocytes in the submucosal layer. In situ hybridization of tumor tissue for
      Epstein-Barr virus (EBV)-encoded small RNA1 as target revealed negative results.
      In stomach carcinoma simulating submucosal tumor, as in this patient,
      preoperative diagnosis is important to plan treatment strategies.

PMID- 11957097
TI  - Laparoscopic gastrectomy for advanced cancer: a technical challenge.

PMID- 11957098
TI  - Perigastric lymph node metastases in gastric cancer: comparison of different
      staging systems.
AB  - BACKGROUND: Perigastric lymph node metastases in gastric cancer are classified
      differently by different staging systems: the distance of positive nodes from the
      primary tumor is considered by the 1987 International Union Against Cancer (UICC)
      TNM system, but not by the Japanese staging system (of the Japanese Research
      Society for Gastric Cancer [JRSGC]); the new UICC-TNM system of 1997 is based on
      the number of involved nodes without differentiating perigastric from regional
      nodes. The aim of the present study was to assess which classification was more
      useful to predict prognosis in gastric cancer patients with metastases to the
      perigastric nodes.METHODS: The results for 107 patients with lymph node
      metastases to the first and second tiers who underwent curative gastrectomy for
      gastric cancer from March 1988 to October 1997 were analyzed. In particular, we
      compared the clinical characteristics and the survival probabilities of: (1)
      patients with metastases to perigastric nodes located within 3 cm from the
      primary tumor, classified as N1; (2) patients with metastases to perigastric
      nodes located 3 cm beyond the primary tumor (N2 in the UICC-TNM and N1 in the
      Japanese classification), classified by us as N1-N2; and (3) patients with
      metastases to the second tier (classified by us as N2). We also assessed the
      number of positive nodes dividing the patients into groups according to the 1997
      UICC TNM system.RESULTS: On multivariate survival analysis, the mortality risks
      in the N1 and N1-N2 patients were comparable (relative risk [RR], N1-N2 versus
      N1, 1.32; 95% confidence interval [CI], 0.53-3.51) and were half the mortality
      risk in N2 patients (RR, N2 versus N1, 2.52; 95% CI, 1.33-4.79). The N1 and N1-N2
      categories, while presenting markedly different distributions in the number of
      metastatic nodes (patients with more than seven metastatic nodes constituted less
      than 20% of the N1 group and more than 60% of the N1-N2 group), showed similar
      prognostic significance.CONCLUSION: In the present series, the distance of
      perigastric nodes from the primary tumor did not seem to exert a significant
      effect on prognosis, and the use of a combined classification based on anatomical
      location (JRSGC) and number of node metastases (UICC-TNM 1997) could be more
      useful than either system alone for prognostic purposes.

PMID- 11957099
TI  - The risk of second malignancy after adjuvant chemotherapy for stomach cancer.
AB  - BACKGROUND: Although many trials have been conducted to evaluate the feasibility
      and effectiveness of adjuvant chemotherapy (ACT) for patients with stomach
      cancer, the benefits of ACT remain unclear. Moreover, some authors have reported
      that ACT increased the incidence of second malignancy. The risk of second
      malignancy was evaluated in patients who underwent treatment for stomach cancer
      in the past 20 years at Osaka Medical Center for Cancer and Cardiovascular
      Diseases.METHODS: The study population consisted of 1925 patients who underwent
      gastrectomies for stomach cancer between the years 1978 and 1992 and who received
      follow-up examinations to check for second malignancies. They included 1114
      patients who underwent surgery only (group A) and 811 who underwent surgery and
      received chemotherapy (group B). The observed incidence of second malignancy (O)
      was compared with the expected incidence (E), calculated by the person-year
      method, using data from the Cancer Registry in Osaka.RESULTS: The average follow
      up period was 7.99 years. The total number of patients with a second malignancy
      was 127 (men, 97; women, 30); 72 patients had the second malignancy in digestive
      organs; 27 in respiratory organs; and 28 in other organs. The relative risks of a
      second malignancy in group A and B patients were 1.05 and 1.02 (differences
      between the two groups were not significant). The relative risks of a second
      malignancy in patients who received ACT with 5-fluorouracil, Tegafur and Uracil,
      and FT207 were 0.79, 1.01, and 1.06, respectively (differences between the groups
      were not significant).CONCLUSION: The risk of second malignancy after
      chemotherapy for stomach cancer was not high in comparison with the expected
      incidence. Adjuvant chemotherapy did not increase the risk of a second
      malignancy.

PMID- 11957100
TI  - Microsatellite instability in patients with gastric remnant cancer.
AB  - BACKGROUND: About 2% of patients who undergo partial distal gastrectomy for
      gastroduodenal diseases develop gastric remnant cancer 10 to 30 years after the
      gastrectomy. It is important in clinical practice to determine a molecular marker
      to identify patients susceptible to gastric remnant cancer.METHODS: We
      investigated nine gastric remnant cancers (from nine individuals who had
      gastrectomies for primary gastric cancer or gastroduodenal ulcer) for
      microsatellite instability (MSI) at six loci, using the polymerase chain reaction
      (PCR). A control group of ten patients with sporadic gastric cancers in the upper
      third of the stomach was also similarly analyzed.RESULTS: MSI was demonstrated in
      eight of nine cancers from the individuals who had had primary gastric cancer or
      gastroduodenal ulcer (88.9%) compared with two of ten cancers from the
      individuals with sporadic gastric cancer in the upper third of the stomach
      (20%).CONCLUSION: These results suggest that one or more MSI is associated with
      remnant gastric cancer after gastrectomy.

PMID- 11957101
TI  - Cardia carcinomas of intestinal type are associated with histologic changes in
      the gastric mucosa.
AB  - BACKGROUND: Previous studies of Japanese patients showed that distal gastric
      carcinomas (of the corpus or the antrum) were associated with histologic changes
      in the non-neoplastic gastric mucosa. These changes (cells with ciliated
      metaplasia, with large and small mucus-negative vacuoles, intramucosal glandular
      cysts, and extensive intestinal metaplasia) were often found in carcinomas of
      intestinal type.METHODS: In the present work, similar mucosal changes were
      searched for in surgical specimens carrying a carcinoma of the cardia. A total of
      12 079 archival histologic sections, corresponding to 563 gastrectomies performed
      in Japanese patients, were analyzed.RESULTS: Of the specimens with cardia
      carcinoma of intestinal type seen in Tokyo ( n = 169) and in Matsuyama ( n =
      168), 53.3% and 63.1% contained intramucosal cysts; 39.6% and 51.8%, ciliated
      metaplastic cells; 34.9% and 30.4%, large vacuolated cells; and 7.7% and 11.9%,
      small vacuolated cells; and 69.8% and 68.5% had high intestinal metaplasia
      scores, respectively. These percentages were significantly higher than those for
      cardia carcinomas of diffuse type in Tokyo ( n = 153) and in Matsuyama ( n = 73),
      in which 30.7% and 34.2% of the specimens had intramucosal cysts; 17.6% and
      17.8%, ciliated metaplastic cells; 14.4% and 9.6%, large vacuolated cells; and
      3.9% and 4.1%, small vacuolated cells; and 43.1% and 39.7% had high intestinal
      metaplasia scores, respectively.CONCLUSION: Thus, similarly to carcinomas of the
      corpus or the antrum, cardia carcinomas of intestinal type are associated with
      histologic changes in the gastric mucosa. The possibility that these changes are
      evoked by environmental factors was entertained.

PMID- 11957102
TI  - Decrease in ICAM-1 expression on gastric cancer cells is correlated with lymph
      node metastasis.
AB  - BACKGROUND: Lymph node metastasis is a frequent type of metastasis in patients
      with gastric cancer. The mechanisms responsible for this type of metastasis,
      however, are not clearly understood. We hypothesize that the immunosurveillance
      system between cancer cells and lymphocytes may be associated with the lymph node
      metastatic process. In this study, we examined the correlation between lymph node
      metastasis and intercellular adhesion molecule-1 (ICAM-1), which mediates the
      immunosurveillance system between tumor cells and cytotoxic lymphocytes, in
      gastric cancer.METHODS: One hundred and forty-three specimens resected from
      patients with gastric cancer were investigated by staining with a monoclonal
      antibody against ICAM-1. We studied the correlation between the expression of
      ICAM-1 and various clinicopathologic factors, as well as infiltration of tumor
      infiltrating lymphocytes (TILs).RESULTS: ICAM-1 expression on gastric cancer
      cells was significantly decreased in patients with lymph node metastasis. The
      infiltration of TILs was associated with ICAM-1 expression level. The prognosis
      of patients with ICAM-1-negative tumors was poorer than the prognosis of those
      with ICAM-1-positive tumors.CONCLUSIONS: These findings suggest that ICAM-1
      expression on cancer cells is closely associated with lymph node metastasis in
      gastric cancer, under the influence of the host immunosurveillance system.

PMID- 11957103
TI  - Redefining surgery for gastric cancer.
AB  - BACKGROUND: Despite encouraging retrospective and non-randomized trials, two
      large prospective, randomized trials of D1 vs D2 resections show double the
      mortality in the D2 group, with no increase in long-term survival. However, the
      D2 resection still offers the only hope of cure when N2 nodes are involved. We
      propose a reclassification of the International Union Against Cancer TNM "N"
      staging to a system with an anatomical basis that is useful in defining the
      surgery performed. Junctional nodes lying between the N1 and N2 tiers will act as
      a guide to surgery. Where these nodes are uninvolved, the probability of gastric
      bed (N2) involvement is low and the radical D2 dissection with its higher
      mortality and morbidity can be avoided.CONCLUSION: Such "stage-appropriate"
      surgery will reduce the number of D2 resections while ensuring that patients with
      N2 disease are not denied curative surgery. A prospective, randomized, controlled
      trial of targeted surgery is required.

PMID- 11957104
TI  - Laparoscopic total gastrectomy with distal pancreatosplenectomy and D2
      lymphadenectomy for advanced gastric cancer.
AB  - The standard lymph node dissection for advanced gastric cancer is a D2
      dissection. Although D2 laparoscopy-assisted total gastrectomy with distal
      pancreatosplenectomy has been reported, no studies have reported a completely
      intra-abdominal laparoscopic approach, because of the technical difficulty of the
      procedure. We successfully performed this novel procedure in two patients with
      advanced gastric cancer located in the upper portion of the stomach. In fact,
      this surgery is technically feasible, and has a potential curability comparable
      with that of open surgery.

PMID- 11957105
TI  - Long-term postoperative survival of a gastric cancer patient with numerous para
      aortic lymph node metastases.
AB  - A56-year-old man with advanced gastric cancer was referred to our hospital.
      Preoperative abdominal computed tomography revealed numerous enlarged lymph
      nodes, including the lymph nodes of the paraaortic region. The patient underwent
      total gastralectomy, splenectomy, left-adrenalectomy and resection of the body
      and tail of the pancreas by Appleby's method, along with paraaortic lymph node
      dissection. Microscopic examination revealed that the tumor was a solid type,
      poorly differentiated adenocarcinoma, which displayed invasion of the serosal
      surface. There were apparently many lymph node metastases. We identified 31
      cancer-positive paraaortic nodes, while the total number of lymph node metastases
      was 81. It was not possible to administer sufficient postoperative adjuvant
      chemotherapy, as the patient experienced postoperative complications, including
      pancreatic fistula and watery diarrhea. Despite the lack of sufficient
      chemotherapy, the patient has subsequently remained disease-free for 9 years and
      3 months, and continues to visit our hospital as an outpatient. In conclusion, we
      wish to emphasize the need for a critical application of paraaortic lymph node
      dissection as one modality of multidisciplinary treatment in patients with
      advanced gastric cancer in whom paraaortic lymph node metastasis is strongly
      suspected preoperatively.

PMID- 11957107
TI  - Squamous cell carcinoma of the stomach.

PMID- 11957106
TI  - Collision carcinoma at the esophagogastric junction.
AB  - Atrue collision carcinoma at the esophagogastric junction is rare. In this
      article, we report colliding double primary cancers of the esophagus and the
      stomach in a 68-year-old man and discuss this entity. Pathological analysis after
      total gastrectomy and partial esophagectomy showed the following findings. Areas
      of squamous differentiation were found on the esophageal side of the tumor and
      were adjacent to normal mucosa, and areas of glandular differentiation were found
      to the gastric side of the tumor and adjacent to normal mucosa. These two tumors
      collided at the esophago-cardiac junction, but there was no intermingling. In one
      lymph node, an independent non-intermingled metastatic adenocarcinoma and
      squamous cell carcinoma were observed. The pathological findings of this case
      satisfy rigorous criteria for collision carcinoma.

PMID- 11957108
TI  - Infectomics: genomics and proteomics of microbial infections.
AB  - The completion of genomic sequences is the greatest triumph of molecular
      reductionism since the discovery of the DNA double helix in 1953. However, the
      utility of reductionism is becoming limited and holistic approaches, including
      theories and techniques, are desperately needed in the postgenomic era. In the
      field of infectious diseases there is an urgent need for global approaches that
      can efficiently, precisely and integratively study structural and functional
      genomics and proteomics of microbial infections (infectomics). The combination of
      new (e.g. DNA and protein microarrays) and traditional approaches (e.g. cloning,
      PCR, gene knockout and knockin, and antisense) will help overcome the challenges
      we are facing today. We assume that the global phenotypic changes (infectomes) in
      microbes and their host during infections are encoded by the genomes of microbial
      pathogens and their hosts, expressed in certain environmental conditions devoted
      to specific microbe-host interactions. Global drug responses (pharmacomes) in
      microbes and their host can be detected by genomic and proteomic approaches.
      Genome-wide approaches to genotyping and phenotyping or expression profiling will
      eventually lead to global dissection of microbial pathogenesis, efficient and
      rapid diagnosis of infectious diseases, and the development of novel strategies
      to control infections. The key fundamental issue of infectious diseases is how to
      globally and integratively understand the interactions between microbial
      pathogens and their hosts by using infectomics. In this review, we focus on the
      events that are considered important in infectomics.

PMID- 11957109
TI  - Large-scale identification of genes important for apical growth in Saccharomyces
      cerevisiae by directed allele replacement technology (DART) screening.
AB  - In Saccharomyces cerevisiae, apical bud growth occurs for a brief period in G1
      when the deposition of membrane and cell wall is restricted to the tip of the
      growing bud. To identify genes important for apical bud growth, we have utilized
      a novel transposon-based mutagenesis system termed DART (Directed Allele
      Replacement Technology) that allows the rapid transfer of defined insertion
      alleles into any strain background. A total of 4,810 insertion alleles affecting
      1,392 different yeast genes were transferred into a cdc34-2 mutant strain that
      arrests in the apical growth phase when grown at the restrictive temperature of
      37 degrees C. We identified 29 insertion alleles, containing mutations in 17
      different genes ( SMY1, SPA2, PAN1, SLA1, SLA2, CBK1, SEC22, FAB1, VPS36, VID22,
      RAS2, ECM33, OPI3, API1/YDR372c, API2/YDR525w, API3/YKR020w, and API4/YNL051w),
      which alter the elongated bud morphology of cdc34-2 cells arrested in the apical
      growth phase. Upon treatment with mating pheromone at 25 degrees C, cells
      containing insertion alleles affecting ten of these genes ( SMY1, SPA2, PAN1,
      SLA1, SLA2, CBK1, FAB1, VPS36, VID22, and API2/YDR525w) form abnormal mating
      projections. Additionally, cells containing insertion alleles affecting SEC22,
      RAS2, API1/YDR372c, API3/YKR020w,and API4/YNL051display severe mating projection
      formation defects at the elevated temperature of 37 degrees C. DART mutagenesis
      has many advantages over traditional mutagenesis methods and will be a useful
      tool for dissecting gene networks important for biological processes.

PMID- 11957110
TI  - Two-hybrid-based analysis of protein-protein interactions of the yeast multidrug
      resistance protein, Pdr5p.
AB  - The ATP-binding cassette (ABC) transporters are a large family of proteins
      responsible for the translocation of a variety of compounds across the membranes
      of both prokaryotes and eukaryotes. The inter-protein and intra-protein
      interactions in these traffic ATPases are still only poorly understood. In the
      present study we describe, for the first time, an extensive yeast two-hybrid
      (Y2H)-based analysis of the interactions of the cytoplasmic loops of the yeast
      pleiotropic drug resistance (Pdr) protein, Pdr5p, an ABC transporter of
      Saccharomyces cerevisiae. Four of the major cytosolic loops that have been
      predicted for this protein [including the two nucleotide-binding domain (NBD)
      containing loops and the cytosolic C-terminal region] were subjected to an
      extensive inter-domain interaction study in addition to being used as baits to
      identify potential interacting proteins within the cell using the Y2H system.
      Results of these studies have revealed that the first cytosolic loop (CL1)-
      containing the first NBD domain--and also the C-terminal region of Pdr5p,
      interact with several candidate proteins. The possibility of an interaction
      between the CL1 loops of two neighboring Pdr5p molecules was also indicated,
      which could possibly have implications for dimerization of this protein.

PMID- 11957111
TI  - Chromosomal regions harboring genes for the work to femur failure in mice.
AB  - The work to failure is defined as the maximum energy bone can absorb before
      breaking, and therefore is a direct test of the risk of fracture. To determine
      the genetic loci influencing work to failure, we have performed a high density
      genome-wide scan in 633 (MRL x SJL) F(2) female mice. Five loci ( P<0.005) with
      significant effects on work to failure were found on chromosomes 2, 7, 8, 9, and
      X, which collectively explained around 20% variance of work to femur failure in
      F(2) mice. Of those, only the QTL on chromosome 9 was concordant with bone
      mineral density (BMD) QTLs. Eight significant interactions ( P<0.01) between
      marker loci were identified, which accounted for an equivalent amount of F(2)
      variance (23%) to combined single QTL effects. Our results demonstrate that most
      of the genetic loci regulating work to failure are different from those for BMD
      in the 7-week-old female mice. If this is also true in humans, this finding will
      challenge the predictive value of BMD for the risk of fracture.

PMID- 11957112
TI  - Gene expression between a congenic strain that contains a quantitative trait
      locus of high bone density from CAST/EiJ and its wild-type strain C57BL/6J.
AB  - Peak bone density is an important determining factor of future osteoporosis risk.
      We previously identified a quantitative trait locus (QTL) that contributes
      significantly to high bone density on mouse chromosome 1 from a cross between
      C57BL/6J (B6) and CAST/EiJ (CAST) mouse strains. We then generated a congenic
      strain, B6.CAST-1T, in which the chromosomal fragment containing this QTL had
      been transferred from CAST to the B6 background. The congenic mice have a
      significantly higher bone density than the B6 mice. In this study we performed
      cDNA microarray analysis to evaluate the gene expression profile that might yield
      insights into the mechanisms controlling the high bone density by this QTL. This
      study led to several interesting observations. First, approximately 60% of 8,734
      gene accessions on GEM I chips were expressed in the femur of B6 mice. The
      expression and function of two-thirds of these expressed genes and ESTs have not
      been documented previously. Second, expression levels of genes related to bone
      formation were lower in congenic than in B6 mice. These data are consistent with
      a low bone formation in the congenic mice, a possibility that is confirmed by
      reduced skeletal alkaline phosphatase activity in serum compared with B6 mice.
      Third, expression levels of genes that might have negative regulatory action on
      bone resorption were higher in congenic than in B6 mice. Together these findings
      suggest that the congenic mice might have a lower bone turnover rate than B6 mice
      and raise the possibility that the high bone density in the congenic mice could
      be due to reduced bone resorption rather than increased bone formation.

PMID- 11957114
TI  - Pharmacokinetics and safety assessment of tosufloxacin tosilate.

PMID- 11957115
TI  - Clinical assessment of tosufloxacin tosilate.

PMID- 11957116
TI  - High frequency of erythromycin A resistance and distribution of mefE and ermB
      genes in clinical isolates of Streptococcus pneumoniae in Japan.
AB  - The ermB and mefE genes are important in terms of their responsibility for
      macrolide resistance in Streptococcus pneumoniae. We investigated the
      distribution of the ermB and mefE genes in erythromycin A-resistant S. pneumoniae
      isolated in our hospital during the period 1995-1998. All amoxicillin-low
      susceptible isolates were considered to be resistant to erythromycin A. All
      isolates with resistance to erythromycin A (minimum inhibitory concentrations
      [MICs], > or =0.5 microg/ml) possessed ermB or mefE genes. The MICs of
      erythromycin A for most mefE-positive isolates ranged from 0.5 to 2 microg/ml. On
      the other hand, approximately 85% of ermB-positive isolates demonstrated high
      level resistance to erythromycin A (MICs, > or =4 microg/ml) while the others
      showed low-level resistance (MICs, 0.5 to 2 microg/ml). In ermB-positive isolates
      with low-level resistance, high-level resistant mutants were selected with a
      frequency of 3.1 x 10(-6)-1.8 x 10(-3) on agar containing 4-32 MIC of
      erythromycin A, whereas in mefE-positive isolates, no high-level resistant
      mutants were detected. Mutants from ermB-positive isolates with low-level
      resistance showed reversibility and heterogeneity. Our data indicated a wide
      distribution of erythromycin A-resistant isolates with mefE or ermB genes among
      amoxicillin-low-susceptible S. pneumoniae in Japan. In addition, it is likely
      that ermB-positive isolates with low-level resistance show heterogeneous high
      level resistance.

PMID- 11957117
TI  - Effect of pazufloxacin mesilate on the serum concentration of theophylline.
AB  - We studied the effect of pazufloxacin mesilate (T-3762), a new fluoroquinolone
      for intravenous administration, on the serum concentration of theophylline.
      Evaluation consisted of comparisons of serum levels of theophylline (when it was
      given alone, as a control), with serum levels of theophylline when T-3762 was
      given concomitantly. We measured the serum concentrations and the urinary
      excretion rates of theophylline in healthy adult male volunteers who were given
      theophylline for 5 days, followed by an i.v. infusion of T-3762. Blood and urine
      samples were investigated on the third and fifth days after the concomitant
      dosing with T-3762, to compare the serum levels and urinary concentrations of
      theophylline with the control values. We found that the serum concentration and
      the urinary excretion rates of theophylline on the fifth day after concomitant
      dosing with T-3762 were significantly increased compared with the levels when the
      volunteers had been given theophylline alone.

PMID- 11957118
TI  - Effectiveness of fosfomycin combined with other antimicrobial agents against
      multidrug-resistant Pseudomonas aeruginosa isolates using the efficacy time index
      assay.
AB  - We investigated the effectiveness of fosfomycin combined with other antibiotics,
      such as piperacillin, cefepime, ceftazidime, imipenem, meropenem, aztreonam,
      gentamicin, or levofloxacin, against 30 Pseudomonas aeruginosa strains, including
      multidrug-resistant strains, isolated from clinical specimens, using the efficacy
      time index (ETI) assay. The assay refers to the result of pharmacokinetics
      obtained from adult men volunteers, and yields an ETI to evaluate the effect of a
      combination of antimicrobial agents. With the ETI, based on serum concentration 3
      h after the administration of two antimicrobial agents, the effectiveness of
      antimicrobial combinations was evaluated as follows: poor, ETI < 0.5; fair, 0.5 <
      or = ETI < 1; good, 1 < or = ETI < 8; and excellent, ETI > or = 8. The
      combination of fosfomycin and cefepime (efficacy rate [excellent plus good],
      76.7%) and fosfomycin/aztreonam (efficacy rate, 76.7%) appeared to be the most
      effective, followed by fosfomycin/meropenem (efficacy rate, 76.6%),
      fosfomycin/imipenem (efficacy rate, 73.3%), fosfomycin/ceftazidime (efficacy
      rate, 70%), fosfomycin/gentamicin (efficacy rate, 70%), fosfomycin/piperacillin
      (efficacy rate, 66.7%), and fosfomycin/levofloxacin (efficacy rate, 66.7%).
      Fosfomycin/cefepime, fosfomycin/aztreonam, and fosfomycin/meropenem may be
      clinically useful in selected patients, particularly for P. aeruginosa. The ETI
      assay provided information on the minimum inhibitory concentration (MIC) of many
      pairs of combined antimicrobial agents simultaneously. The ETI assay may be a
      useful technique with which to investigate the effect of combinations of
      antimicrobial agents against P. aeruginosa, including multidrug-resistant
      strains.

PMID- 11957119
TI  - Molecular epidemiological study of vertical transmission of vaginal Lactobacillus
      species from mothers to newborn infants in Japanese, by arbitrarily primed
      polymerase chain reaction.
AB  - We investigated mother-to-newborn infant transmission of Lactobacillus species in
      Japanese by the typing of isolates from the vagina of pregnant women and stool
      specimens from their newborn infants. All infants were born by uncomplicated
      vaginal delivery and were basically fed breast milk. Lactobacillus strains were
      fingerprinted by arbitrarily primed polymerase chain reaction (AP-PCR), using
      ERIC1R and ERIC2 primers. Of 86 pregnant women tested, 71 (82.6%) were positive
      for vaginal lactobacilli. At 5 days after birth, 24 (33.8%) of the 71 infants
      whose mothers were lactobacilli-positive had fecal lactobacilli, while only 1
      (6.7%) of the 15 infants delivered from the vaginal lactobacilli-negative mothers
      was lactobacilli-positive ( P < 0.01). Lactobacillus crispatus was the most
      prevalent species of vaginal lactobacilli in mothers and of fecal lactobacilli in
      infants at 5 days of age, whereas Lactobacillus gasseri was the most common in
      infants at 1 month of age. Identification to the species level, followed by AP
      PCR typing, demonstrated that 23.3% of the 86 infants were likely to be colonized
      in the intestine by the vaginal lactobacilli of their mothers, and that only 2 of
      the infants retained the same vaginal lactobacilli until 1 month of age. These
      results suggest that approximately one-fourth of infants acquire vaginal
      lactobacilli from their mothers at birth, and that the acquired lactobacilli do
      not last in the intestine of the infant long-term, but rather, are replaced by
      ones from milk or unknown sources after birth. AP-PCR with primers ERIC1R and
      ERIC2 is indicated as a potential tool for the typing of Lactobacillus strains.

PMID- 11957120
TI  - Differentiation of beta-lactamase-negative ampicillin-resistant Haemophilus
      influenzae from other H. influenzae strains by a disc method.
AB  - We established breakpoints for differentiating ampicillin (ABPC)-susceptible
      strains from resistant strains among Haemophilus influenzae isolates according to
      susceptibility to various beta-lactam antibiotics, using a disc method.
      Susceptibility testing of isolates for 13 beta-lactam agents was followed by
      analysis of the resistance genes, using a polymerase chain reaction (PCR) to
      identify the TEM-1 beta-lactamase gene ( bla) and the ftsI gene encoding
      penicillin-binding protein (PBP) 3, which affects beta-lactam minimum inhibitory
      concentrations (MICs). A total of 228 H. influenzae isolates were classified into
      114 beta-lactamase-negative, ABPC-susceptible (BLNAS) strains; 29 beta-lactamase
      negative, ABPC-resistant (BLNAR) strains; 53 low-BLNAR strains with a low degree
      of ABPC resistance; 27 TEM-1-producing strains (BLPAR); and 5 strains with ftsI
      gene mutations in addition to TEM-1 production (BLPACR) according to the PCR
      results. To identify resistant strains by disc-method susceptibility testing, the
      zone of inhibition was measured for ABPC (10 microg/disc), cefaclor (30
      microg/disc), cefpodoxime (10 microg/disc), and cefdinir (5 microg/disc) discs.
      Strains were identified as BLNAS without resistant genes when the diameter was >
      or =27 mm for the ABPC disc and > or =21 mm for the cefaclor disc. Other strains
      were identified as BLNAR when the diameter was < or =22 mm for the cefpodoxime
      disc and < or =17 mm for the cefdinir disc. Remaining strains were identified as
      low-BLNAR. These criteria differentiated resistance types with high accuracy. A
      discrepancy was noted between genetic results and disc-testing breakpoints for
      differentiating resistant from susceptible H. influenzae. A disc-testing
      breakpoint for cefditoren (5 microg/disc) was proposed, with the susceptibility
      statistically defined as a diameter of > or =24 mm, which corresponds to the
      breakpoint (1 microg/ml) of the microdilution method recommended by the Japanese
      Society of Chemotherapy.

PMID- 11957121
TI  - Multidrug-resistant Pseudomonas aeruginosa isolated from the urine of patients
      with urinary tract infection.
AB  - We report the clinical courses of 3 patients with urinary obstruction who
      developed acute pyelonephritis caused by multidrug-resistant (MDR) Pseudomonas
      aeruginosa. Genome fingerprinting was performed to clarify the route of cross
      infection, and an imipenem-resistance gene was detected by the polymerase chain
      reaction (PCR) method. The study included 17 patients at our institute who had
      urinary tract infections caused by P. aeruginosa between January and December
      1997. MDR was defined as that when all the minimum inhibitory concentrations
      (MICs) were determined to show resistance according to the breakpoints
      recommended by the National Committee for Clinical Laboratory Standards (NCCLS)
      for P. aeruginosa. Pulse-field gel electrophoresis (PFGE) was carried out for
      genome fingerprinting. PCR was used to detect the metallo-beta-lactamase gene (
      bla(IMP)). Three strains were revealed for MDR. The strains were isolated from
      the 3 patients with urinary tract obstruction who developed acute pyelonephritis.
      The treatment consisted of urinary drainage for the obstructed urinary tract and
      parenterally administered antimicrobials. Although none of the strains was
      susceptible to any antimicrobials, all patients had favorable outcomes. PFGE
      revealed that two strains had an identical genotype, implying cross-infection
      between the patients. The bla(IMP) gene was not detected in any of the three
      strains. In febrile patients with urinary tract infection caused by MDR P.
      aeruginosa, treatment for urinary obstruction is strongly recommended. Initial
      empirical chemotherapy with antimicrobials to which the organism is not
      susceptible is often inevitable. Because there was epidemiological evidence of
      cross-infection with MDR P. aeruginosa, countermeasures against nosocominal
      infection are warranted.

PMID- 11957122
TI  - Present status of hepatitis virus-associated hepatocellular carcinoma in Nagasaki
      Prefecture, Japan: a cross-sectional study of 1019 patients.
AB  - The present study was designed to determine the frequency of hepatitis B virus
      (HBV) and hepatitis C virus (HCV) infection in patients with hepatocellular
      carcinoma (HCC) in Nagasaki Prefecture, Japan. We examined the clinical features
      of 1019 patients with HCC who visited our hospitals between January and December
      1999. The ratio of men to women was 709 : 310, and the peak incidence of HCC was
      in the seventh decade of life in both men and women. In the majority of the
      patients, HCC showed association with HCV infection (74%) compared with HBV
      infection (17%). HBV-associated HCC was more common in young patients, while HCV
      associated HCC was more common in patients with a history as a "daily drinker",
      or with a history of blood transfusion, liver cirrhosis, and persistently high
      serum transaminases before the diagnosis of HCC. HCC was initially suspected by
      ultrasonography or computed tomography in 776 of the 874 patients for whom there
      was a history of mode of detection of HCC (89%). Tumor size at the time of
      diagnosis of HCC in patients who had been regularly followed up for liver
      diseases at our hospitals was significantly smaller than that in patients who
      were not followed up regularly before the diagnosis ( P < 0.01). Our results
      indicate that the proportions of patients with HBV or with HCV infection among
      HCC patients in Nagasaki Prefecture are similar to those found in a nationwide
      survey in Japan, and there are some differences between the clinical
      manifestations of HBV- and HCV-associated HCC. Our results emphasize the
      importance of close follow-up for the high-risk group (i.e. those with HBV- or
      HCV-associated chronic liver diseases) for the early detection of HCC.

PMID- 11957123
TI  - Intrafamilial transmission of Helicobacter pylori: the association between a
      parent and an offspring with respect to the presence of anti-CagA antibody.
AB  - In this study, we examined whether the transmission of Helicobacter pylori
      occurred in married couples. We also examined whether a correlation existed
      between H. pylori seropositivity in a parent and an offspring, which may be
      related to H. pylori transmission. A cross-sectional study of residents living in
      a rural area in Japan was conducted in 1998. The study population consisted of
      1910 volunteers, aged from 22 to 79 years, residing in this area. We
      serologically confirmed the presence of the antigen, CagA (cytotoxin-associated
      gene A), of H. pylori, using a recombinant CagA antigen, in addition to examining
      for antibodies to H. pylori, as determined by an IgG-specific enzyme immunoassay.
      The data were analyzed using logistic regression models. A significant
      association of H. pylori seropositivity was observed ( P < 0.001) in married
      couples, but no significant difference with respect to the presence of anti-CagA
      antibodies was observed in the married couples with H. pylori seropositive
      results ( P = 0.053). The odds ratio was 8.08 (95% confidence interval [CI], 1.39
      40.05) for infection in offspring with seropositive mothers and 2.93 (95% CI,
      0.25-33.85) for infection in offspring with seropositive fathers when compared
      with seronegative fathers or mothers as the reference. There was a concordance
      between the presence or absence of anti-CagA antibodies in 11 of 13 groups of
      mothers and offspring (84.6%) compared with concordance in 6 of 14 groups of
      fathers and offspring (42.9%; P < 0.05). Our results suggest that maternal
      influence is likely to be more powerful than paternal influence in the
      transmission of H. pylori.

PMID- 11957124
TI  - Differentiating between bacterial and viral infection by measuring both C
      reactive protein and 2'-5'-oligoadenylate synthetase as inflammatory markers.
AB  - This study aimed to find a method to distinguish between bacterial and viral
      infection by measuring inflammatory markers in the early phase of the illness. We
      examined the activity of acute phase proteins, including C-reactive protein
      (CRP), serum amyloid A (SAA), and 2'-5'-oligoadenylate synthetase (2-5A
      synthetase), in sera obtained from children with bacterial and viral infections
      that were diagnosed by isolation of the pathogen or by positive serology.
      Increases in levels of CRP and SAA generally paralleled each other. In the acute
      stage of bacterial infections, CRP levels were moderately or highly increased and
      2-5A synthetase levels were normal, whereas in viral infections, CRP levels were
      normal or slightly increased and 2-5A synthetase levels were increased. To better
      distinguish between bacterial and viral infection we used the ratio of CRP (mg/l)
      to 2-5A synthetase (pmol/dl) x10 as the differential index. The values for this
      index in bacterial infections ranged from 3.9 to 50, and were higher than the
      values in viral infections, which ranged from 0 to 0.9. We propose that the
      measurement of both CRP and 2-5A synthetase during the acute phase of illness
      (within 5 days of onset) is of value to determine whether the infection is caused
      by a bacteria or virus.

PMID- 11957125
TI  - A remarkable reduction in the susceptibility of Neisseria gonorrhoeae isolates to
      cephems and the selection of antibiotic regimens for the single-dose treatment of
      gonococcal infection in Japan.
AB  - We compared the susceptibilities of 100 Neisseria gonorrhoeae isolates obtained
      from January to June 2000 to a variety of antimicrobial agents, including various
      cephems, with the susceptibilities of 55 isolates obtained from May to December
      1995. In 11 of the 15 cephems tested, the MIC50 (minimum inhibitory concentration
      for 50% of isolates) ratios, calculated by dividing the MIC50 for isolates from
      2000 by that for isolates from 1995, showed 4-fold to 16-fold differences. The
      MIC90 ratios of cefodizime and cefditoren showed only a 1-fold and 2-fold
      difference, respectively. However, the MIC90 ratios of the remaining 13 cephems
      showed 4-fold to 64-fold differences. We selected the most favorable antibiotic
      regimens for the single-dose treatment of gonorrhea in Japan according to the
      antigonococcal activity and pharmacokinetics, based on the criterion (therapeutic
      time) proposed by Moran and Levine i.e., the regimen should produce a
      concentration in the serum or plasma at least four times that of the MIC90 value
      for at least 10 h. Of the 20 single-dose regimens evaluated, only ceftriaxone 1 g
      intravenously and cefodizime 1 g intravenously were found to have a therapeutic
      time of more than 10 h for the isolates from 2000. Our results indicated that the
      susceptibilities of the isolates from 2000 to all the cephems tested, except for
      cefditoren and cefodizime, decreased remarkably in comparison with the
      susceptibilities of the isolates from 1995, while parenteral ceftriaxone 1 g and
      cefodizime 1 g appeared to be the most favorable single-dose regimens for the
      treatment of gonococcal infections in Japan.

PMID- 11957127
TI  - Efficacy of ivermectin for chronic strongyloidiasis: two single doses given 2
      weeks apart.
AB  - We assessed the efficacy and adverse effects of ivermectin for the treatment of
      chronic strongyloidiasis. Fifty patients were treated with a single dose of
      ivermectin at approximately 200 microg/kg, and the dose was repeated 2 weeks
      later. The eradication rate was 96% (48 of 50 patients) at 2 weeks after the
      first dose and 98% at 2 weeks after the second dose (49 of 50 patients). In the
      latter cases, no recurrence was noted at the end of the 4-month post-treatment
      follow-up period. The gastrointestinal symptoms observed most frequently before
      the treatment were borborygmus, constipation, and diarrhea. These symptoms
      improved in the majority of patients after the treatment. Side effects, including
      nausea and vomiting, occurred in 1 patient (2%), but these were mild and
      transient. Although abnormal values in laboratory tests were observed in 4
      patients (8%), they were mild, and no particular clinical care was required.
      Thus, ivermectin showed an excellent antihelminthic effect, with little toxicity.
      Our results indicate that a regimen of two single doses of 200 microg/kg
      ivermectin, given 2 weeks apart, is clinically suitable for the treatment of
      chronic strongyloidiasis.

PMID- 11957126
TI  - Differences in postoperative morbidity rates, including infection and dry socket,
      and differences in the healing process after mandibular third molar surgery in
      patients receiving 1-day or 3-day prophylaxis with lenampicillin.
AB  - The aim of this study was to examine the effect of antibiotic prophylaxis for
      mandibular third molar surgery from the viewpoint of the duration of
      administration. A comparative study was conducted on postoperative infection, dry
      socket, and the healing process in 178 healthy patients receiving 1-day or 3-day
      prophylaxis with lenampicillin (LAPC; 1.5 g/day). Postoperative infection
      developed in only 1 (1.1%) of the 91 patients in the 3-day group, while there was
      no patient with infection in the 87 patients in the 1-day group. Dry socket
      developed in 8.0% of the 87 patients in the 1-day group and in 7.7% of the 91
      patients in the 3-day group. However, the incidence of these complications, in
      relation to the degree of impaction of the molars, did not significantly differ
      between the 1-day and 3-day groups. Scores indicating clinical symptoms for the 7
      days after surgery also reflected no significant difference between the groups,
      irrespective of the degree of impaction. These results suggest that 1-day therapy
      with LAPC in our regimen may at least be recommended as a prophylaxis for
      mandibular third molar surgery in medically healthy patients.

PMID- 11957128
TI  - Destructive pulmonary embolism in a patient with community-acquired
      staphylococcal bacteremia.
AB  - We report a 17-year-old man with destructive pulmonary embolism caused by
      Staphylococcus aureus bacteremia. The patient was not immunocompromised and had
      neither underlying diseases nor risk factors, such as concomitant influenza viral
      infection, which exacerbate staphylococcal infections. The rapid and extensive
      progression of pulmonary involvement in all lung fields make this a rare case;
      there have been few reports in the literature describing a similar radiographic
      appearance in patients with community-acquired staphylococcal bacteremia. In
      vitro studies did not demonstrate the production of enterotoxins or toxic shock
      syndrome toxin 1 (TSST-1) by the isolated strain, but genetic analysis detected
      Panton-Valentine leukocidine gene from the strain. Subsequent empyema with
      bilateral pneumothorax was prolonged because of superinfection with both
      methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Optional
      surgical treatments, including thoracostomy and thoracopneumoplasty, finally
      improved his condition.

PMID- 11957129
TI  - An autopsy case of disseminated mucormycosis in a neutropenic patient receiving
      chemotherapy for the underlying solid malignancy.
AB  - Mucormycosis is a rare, opportunistic infection caused by fungi of the order
      Mucorales, class Zygomycetes. These fungi produce fatal opportunistic infections
      in immunocompromised patients, especially in those with severe neutropenia.
      Recently, mucormycosis has become more widespread, because potent,
      myelosuppressive chemotherapies are performed more often than before.
      Nevertheless, this infection rarely occurs in patients with solid malignancies.
      Here, we describe an autopsy case of disseminated mucormycosis in a neutropenic
      patient who was receiving chemotherapy for an underlying solid malignancy. A 31
      year-old Japanese man received cytotoxic chemotherapy with etoposide for the
      pulmonary metastasis of a secondary malignant fibrous histiocytoma. This patient
      had long been treated with chemotherapeutic agents for this solid cancer and for
      the preceding eosinophilic granuloma, both of which were highly resistant to the
      therapy. During the treatment with etoposide, his neutrophil count declined to
      less than 100/microl. He presented with high fever and severe dyspnea. Pneumonia
      was highly suspected. The chemotherapy was discontinued, and granulocyte colony
      stimulating factor was administered. Although the neutrophil count recovered, the
      pneumonia progressed. The patient experienced respiratory failure and died 17
      days after the onset of this episode. An autopsy revealed dissemination of
      mucormycosis not only in the lungs but also in the liver, the spleen, the kidney,
      and in the digestive tract. The therapy-related severe neutropenia, and the
      probable impairment of the immune system, because of the previous chemotherapies,
      would have been responsible for this fatal infection.

PMID- 11957130
TI  - Effect of direct infusion of antifungal agent on invasive pulmonary aspergillosis
      in a patient with acute leukemia.
AB  - Invasive pulmonary aspergillosis is a serious problem in the treatment of
      patients with acute leukemia. A 52-year-old woman with acute myeloid leukemia
      developed invasive pulmonary aspergillosis during remission induction
      chemotherapy. Initially, we treated her with a continuous intravenous drip
      infusion of amphotericin B, together with itraconazole, given orally. A
      peripheral crescentic cavity formed in the fungal lesion after the number of
      neutrophils recovered, and we therefore performed a direct infusion of miconazole
      into the cavity transbronchially. The lung lesion resolved dramatically shortly
      after this treatment. In this patient, the transbronchial infusion of an
      antifungal agent seemed to have been very useful for bringing about prompt
      resolution of the fungal lesion.

PMID- 11957131
TI  - Central venous catheter-related Rhodotorula rubra fungemia.
AB  - With the increased use of indwelling central venous catheters, increasing numbers
      of cases of Rhodotorula fungemia have been observed in patients with neoplasia
      and neutropenia. In most patients with catheter-related Rhodotorula fungemia, the
      condition has been treated with broadspectrum antibiotics. We report two cases of
      central venous catheter-related Rhodotorula rubra fungemia that occurred in
      patients with acute myeloblastic leukemia. Both patients were in a state of
      neutropenia. One patient was treated with amphotericin B and his central venous
      catheter was removed, but he died of Klebsiella pneumoniae bacteremia. The other
      patient was treated with amphotericin B and discharged, with a central venous
      catheter, after recovery from neutropenia. Although the management of catheter
      related Rhodotorula fungemia infections remains controversial, resolution of the
      underlying disease is more important than catheter removal for recovery from
      Rhodotorula rubra fungemia.

PMID- 11957132
TI  - The percentage of superantigen-reactive T cells in peripheral blood significantly
      decreases before massively increasing in patients with neonatal TSS-like
      exanthematous disease in the early acute phase.
AB  - The behavior of Vbeta2(+) T cells reactive with the pathogenic superantigen toxic
      shock syndrome toxin-1 (TSST-1) was examined in 12 patients with neonatal TSS
      like exanthematous disease (NTED). In 8 patients, the percentage of Vbeta2(+) T
      cells in peripheral blood (PB) T cells had increased to three times the level in
      methicillin-resistant Staphylococcus aureus (MRSA)-free neonatal controls, when
      examined on days 4 to 7 of life. In the remaining 4 patients, however, the
      percentage of Vbeta2(+) T cells was significantly low, i.e., ranging from less
      than 10% to 30% of the control level, when they were examined on days 4 to 8 of
      life, and the percentage increased dramatically several days later, indicating
      that these patients actually had NTED. We recommend that, in patients who are
      suspected of having NTED, when an increase in Vbeta2(+) T cells is not observed
      in a comparatively early period of the illness, reassessment of the Vbeta2(+) T
      cells should be carried out 2 to 4 days later, to obtain a conclusive diagnosis
      of NTED.

PMID- 11957133
TI  - In-vitro activity of moxifloxacin and other fluoroquinolones against Chlamydia
      species.
AB  - The in-vitro activity of moxifloxacin, a new fluoroquinolone, against Chlamydia
      species was investigated. The minimal inhibitory concentration of moxifloxacin
      for 10 standard strains of different Chlamydia species and 15 wild-type strains
      of Chlamydia pneumoniae isolated in Japan, which were morphologically different
      from clinical isolates from the United States, ranged from 0.031 to 0.125
      microg/ml. The activity of moxifloxacin was almost the same as those of
      sparfloxacin, and it was 16, 8, 2, and 2 times more active than ciprofloxacin,
      levofloxacin, grepafloxacin, and tosufloxacin, respectively. The minimal
      chlamydiacidal concentration of moxifloxacin ranged from 0.031 to 0.125
      microg/ml. These results suggest that moxifloxacin has potential effects against
      Chlamydia species.

PMID- 11957134
TI  - The percentage of superantigen-reactive T cells in peripheral blood significantly
      decreases before massively increasing in patients with neonatal TSS-like
      exanthematous disease in the early acute phase.

PMID- 11957136
TI  - Is the Epstein-Barr virus infection relevant in lymphomagenesis?

PMID- 11957135
TI  - A major predisposition locus for severe obesity, at 4p15-p14.
AB  - Although the predisposition to morbid obesity is heritable, the identities of the
      disease-causing genes are largely unknown. Therefore, we have conducted a
      genomewide search with 628 markers, using multigenerational Utah pedigrees to
      identify genes involved in predisposition to obesity. In the genomewide search,
      we identified a highly significant linkage to high body-mass index in female
      patients, at D4S2632, with a multipoint heterogeneity LOD (HLOD) score of 6.1 and
      a nonparametric linkage (NPL) score of 5.3. To further delineate the linkage, we
      increased both the marker density around D4S2632 and the size of our pedigree
      data set. As a result, the linkage evidence increased to a multipoint HLOD score
      of 9.2 (at D4S3350) and an NPL score of 11.3. Evidence from almost half of the
      families in this analysis support this linkage, and therefore the gene in this
      region might account for a significant percentage of the genetic predisposition
      to severe obesity in females. However, further studies are necessary to clarify
      the effect that this gene has in males and in the general population.

PMID- 11957137
TI  - Epstein-Barr virus association and ALK gene expression in anaplastic large-cell
      lymphoma.
AB  - Anaplastic large cell lymphoma of T/null-cell type (ALCL) is associated with a
      characteristic genetic abnormality t(2;5) that results in the NPM-ALK chimeric
      gene and the protein product derived thereof. In 10% to 20% of ALCLs, the
      translocation partners of the ALK gene are genes other than NPM (variant
      translocations). ALK gene expression limited to the cytoplasm implies a variant
      translocation. In this study, we have investigated 46 cases of ALCL for
      expression and localization of ALK protein and its association with Epstein-Barr
      virus (EBV) (by hybridization to EBV-encoded nuclear RNA-1 [EBER-1] and
      immunostaining for LMP-1). ALCL patients with a null cell phenotype were
      significantly younger as compared with those of T-cell phenotype (mean age: 28
      years v 42 years; P =.018). Sixteen of 46 ALCL cases (34%) were ALK positive. ALK
      positive patients were significantly younger (mean age: 25 years for those with
      both cytoplasmic and nuclear staining; 22 years for those with exclusive
      cytoplasmic staining; and 41 years for those negative for the ALK gene; P =.023).
      EBER-1 was detected in 9 of 46 cases (20%), and LMP-1 expression was noted in 5
      of them. By polymerase chain reaction analysis, all EBV-associated cases that
      were investigated showed type I EBV. Whereas 2 of 23 T-cell ALCLs (9%) were EBER
      1+, and 7 of 23 null-cell ALCLs (30%) showed EBV association (P =.057). EBV
      association was seen in 20% of ALK-negative cases, in 0% of cases with ALK gene
      expression in both nucleus and cytoplasm, and in 60% of cases with ALK gene
      expression exclusively in the cytoplasm (P =.02). Further, although ALK-positive
      EBER-1+ cases were LMP-1 negative, ALK-negative-EBER-1+ cases were LMP-1
      positive. Our study raises the question whether EBV might have an etiological
      role in the evolution of ALCLs that lack classical t(2;5).

PMID- 11957138
TI  - Lymphomas of the oral cavity: histology, immunologic type, and incidence of
      Epstein-Barr virus infection.
AB  - The purpose of this study was to determine the histologic class and immunologic
      phenotype of lymphomas presenting initially in the oral cavity and whether this
      correlated to a high incidence of Epstein-Barr virus (EBV) infection as has been
      reported with lymphomas in the nasal cavity. Seventy-one cases of oral lymphomas
      from the oral pathology referral service were analyzed retrospectively. They were
      classified according to the Revised European American Lymphoma (REAL)
      classification system using routine immunohistochemistry. EBV infection was
      determined by detection of early viral RNA sequences (EBER) and latent membrane
      protein (LMP-1) expression. Only non-Hodgkin's lymphomas were observed, with a
      female predominance of 2:1. They were primarily of B-cell origin and
      histologically classified mainly as large B-cell type (68%); T-cell lymphomas
      were rare (8%). EBV infection was observed in 14% of the B-cell lymphomas, an
      incidence rate higher than that reported in studies of B-cell lymphomas not
      located in the oral cavity but not as high as that observed in pleomorphic T-cell
      lymphomas (all sites, 36%) or nasal cavity T-cell lymphomas (nearly 100%).
      Interestingly, EBV proliferation did not correlate with expression of either Bcl
      2 or p53.

PMID- 11957140
TI  - Estrogen receptor expression in giant cell tumors of the bone.
AB  - Giant cell tumors (GCTs) of the bone are primary skeletal neoplasms that behave
      intermediately between a true benign and an overtly malignant neoplasm. For two
      decades, controversial reports have found estrogen receptor (ER) expression in
      isolated cells or small numbers of samples from these tumors. In this report, we
      studied by immunohistochemistry 88 cases of GCTs and found that 51% of the
      samples expressed ER. Furthermore, we found that a subset of seven samples
      analyzed for ER expression by western blot was positive. To address whether the
      ER expressed in these samples could be functional, isolated cells were exposed to
      beta-estradiol and growth curves were generated. Exposure of cells to beta
      estradiol induced a small but significant growth in the cells. These results
      strongly support that GCTs of the bone express functional ERs.

PMID- 11957139
TI  - Differential expression of p53 gene family members p63 and p73 in head and neck
      squamous tumorigenesis.
AB  - p73 and p63 are recently cloned genes that share considerable structural and
      functional homologies with the p53 tumor suppressor gene. These genes, unlike
      p53, express multiple mRNA isoforms with variable biologic functions, and their
      suppressor nature has yet to be confirmed. To determine the interrelationship
      between these genes in the tumorigenesis of head and neck squamous carcinoma
      (HNSC), we performed immunohistochemical analyses of their protein products and
      compared the data with clinicopathologic parameters in 38 patients. In
      histologically normal epithelium, p53 and p73 showed similar basal and/or
      parabasal expression, but that of p53 was weaker and discontinuous. p63 staining
      was noted in more suprabasal cellular layers and was stronger. In dysplasias, all
      three markers manifested variable but gradual increase in extent and intensity of
      cellular expression with histologic progression. In carcinomas, p63 was the most
      frequently expressed (94.7%), followed by p73 (68.4%) and p53 (52.6%).
      Significant statistical correlation was noted only between p63 and p73
      expressions (P =.04). Although no statistical correlation was found between p53
      and p63 or p73, p53-negative tumors overexpressed either p63 or p73. p73
      expression was associated with distant metastasis and perineural/vascular
      invasion. Our study indicates that (1) p63 and p73 expression may represent an
      early event in HNSC tumorigenesis, (2) the lack of correlation between p73 or p63
      and p53 expression suggests an independent and/or compensatory functional role,
      (3) p73 expression may play a part in HNSC progression, and (4) p73 and p63 may
      function as oncogenes in the development of these tumors.

PMID- 11957141
TI  - Expression of p53 gene product and cell proliferation marker Ki-67 in Ewing's
      sarcoma: correlation with clinical outcome.
AB  - Overexpression of tumor suppressor gene p53, cell proliferation nuclear antigen
      Ki-67, and proto-oncogene HER-2/neu are associated with poor prognosis in some
      tumors. We studied p53, Ki-67, and HER-2/neu immunohistochemical expression in
      archival biopsies of 37 patients with Ewing's sarcoma (ES). Patients with ES were
      treated at four Israeli hospitals between 1982 and 2000. Formalin-fixed paraffin
      embedded tissue sections were stained by immunohistochemistry for p53, Ki-67, and
      HER-2/neu. More than 300 cells were counted on each slide, and the percentage of
      positively stained nuclei was computed. p53 overexpression was defined as nuclear
      staining of >2.3% of cells, Ki-67 overexpression as nuclear staining of >8.3%
      malignant cells. HER-2/neu staining was scored semiquantitatively on a scale of 0
      to 4+. Twenty-two of 37 patients are alive and well, with mean follow-up time of
      38 months. There was overexpression of p53 in 16 patients (43%) and of Ki-67 in
      21 patients (57%). The correlation between p53 and Ki-67 overexpressions was
      0.61. We found no overexpression of HER-2/neu. Median relapse-free survival (RFS)
      was statistically significantly shorter for patients with p53 overexpression (25
      months) than for patients with negative staining (>92 months). The prognostic
      value of p53 overexpression was also significant after adjusting for tumor
      location and age. Median RFS was shorter for patients with positive Ki-67
      staining (40 months) than for patients with negative staining (80 months) but did
      not reach statistical significance. Our study suggests that p53 is a predictor of
      RFS in patients with ES. More patients must be studied to assess the validity of
      this observation.

PMID- 11957143
TI  - Re-evaluation of chorioamnionitis and funisitis with a special reference to
      subacute chorioamnionitis.
AB  - Our purpose is to prove that prolonged inflammation of the chorionic plate, which
      we have termed subacute chorioamnionitis (SCAM), is a distinctive entity and
      should be differentiated from acute chorioamnionitis (ACAM) because it is an
      excellent prognostic indicator of chronic lung disease (CLD), including Wilson
      Mikity syndrome (WMS). Ninety singleton placentas with stage-3 chorioamnionitis
      were delivered at 23 to 32 weeks of gestation during 1993 to 1996, and the
      infants survived more than 28 days. There were 49 placentas with stage 3 SCAM, 33
      placentas with stage 3 ACAM, and 8 placentas with subacute necrotizing funisitis
      (SNF) and without inflammation of the chorionic plate. Fifty-three of gestation-
      and birthweight-matched placentas without chorioamnionitis were selected as
      control. To determine the risk factors for CLD, 27 clinical and 6 histological
      variables were analyzed. Logistic regression analysis showed that amniotic
      necrosis (AN) (P =.0168) and low birthweight (P =.0341) were the major
      contributing risk factors for CLD. SNF was not significantly related to CLD.
      Patients with SCAM (AN+, SNF-) were highly susceptible to CLD. In conclusion,
      SCAM, especially when associated with AN, seems to be a unique prognostic
      indicator of CLD.

PMID- 11957142
TI  - Expression of thyroid transcription factor-1 in the spectrum of neuroendocrine
      cell lung proliferations with special interest in carcinoids.
AB  - The World Health Organization's classification of lung tumors separately
      categorizes neuroendocrine (NE) lung tumors, small cell lung carcinoma (SCLC),
      and large cell neuroendocrine carcinoma (LCNEC) as high-grade NE malignancies and
      carcinoids (typical, [TC] and atypical [AC]) as low- and intermediate-grade
      malignancies. Although these NE tumors are considered with NE hyperplasia (NEH)
      and tumorlets as part of a spectrum of NE proliferations, their derivation from a
      common progenitor cell has not received full agreement. With the aim of refining
      their differential diagnosis and extending our understanding of their
      histogenesis, we studied the expression of thyroid transcription factor-1 (TTF
      1), a transcription factor that regulates lung morphogenesis and differentiation,
      along the spectrum of NE lung tumors. Two hundred and twenty- seven NE
      proliferations and tumors were immunostained with TTF-1 antibody. Positive
      immunostaining for TTF-1 was detected in 47 of 55 (85.5%) pure SCLCs, in 31 of 64
      (49%) pure LCNECs, but in none of 15 NEHs, 23 tumorlets, or 50 carcinoid tumors
      (27 TCs and 23 ACs). In 19 of 20 (95%) combined SCLCs and LCNECs, TTF-1
      expression was identical in both NE and non-NE components. These results show
      that TTF-1 is not expressed in normal and hyperplastic NE cells or in carcinoids,
      but is expressed in high-grade NE proliferations and in lung adenocarcinomas.
      This challenges the concept of a spectrum of NE proliferations and tumors and
      lends credence to the alternative hypothesis of a common derivation for SCLC and
      non-SCLC including LCNEC, with carcinoids deriving from a different stem cell.

PMID- 11957144
TI  - Loss of heterozygosity analysis of cutaneous melanoma and benign melanocytic
      nevi: laser capture microdissection demonstrates clonal genetic changes in
      acquired nevocellular nevi.
AB  - The molecular pathology of the common nevocellular nevus (NCN) and its
      relationship to the genetic model of malignant melanoma (MM) progression has not
      been fully characterized. We used laser capture microdissection of archival
      formalin-fixed material to study 34 melanocytic lesions (19 MM and 15 NCN).
      Twelve of the 15 NCN were acquired, 3 of which were congenital; none had
      dysplastic features. Ten polymorphic markers on five chromosomal regions (1p36,
      6q22-23.3, 8p22-24, 10q23, and 11q23) were selected for loss of heterozygosity
      (LOH) analysis, based on previous studies demonstrating involvement in MM
      pathogenesis and progression. Loss of heterozygosity at any allelic locus was
      observed in 18 of 19 (95%) MM and in 9 of 15 (60%) NCN. Of the three congenital
      nevi analyzed, none showed LOH at any informative locus. The frequency of allelic
      loss was highest in the MM at 6q22-23.3 (64%), followed by 10q23 (62%), 8p22-24
      (43%), 11q23 (43%), and 1p36 (13%). In the 15 NCN, the most frequent allelic
      losses were detected at 6q22-23.3 (29%), 1p36 (27%), and 10q23 (25%), with lower
      frequencies of LOH at 11q23 (10%) and 8p22-24 (7%). LOH at a single polymorphic
      marker, D6S1038, was detected in 70% of the MM and in 36% of the NCN, suggesting
      the presence of putative tumor-suppressor genes (TSGs) critical in melanocytic
      neoplasia at 6q22-23.3. The presence of clonal genetic alterations in acquired
      NCN justifies their classification as a benign neoplasm. The pattern of LOH in
      NCN is not random; rather, the relative frequencies of LOH at the chromosomal
      regions examined are consistent with a multistep model of MM progression that
      begins with NCN. Molecular analysis of NCN reiterates established epidemiologic
      and morphologic notions that NCN are precursor lesions for MM.

PMID- 11957145
TI  - Distinct patterns of p27/KIP 1 gene expression in hepatoblastoma and prognostic
      implications with correlation before and after chemotherapy.
AB  - Over the past 3 years, numerous studies have examined the diagnostic and
      prognostic significance of p27/Kip1 expression in various tumors. Almost all
      studies report decreased p27 expression in more aggressive tumors. Information
      about morphologic changes due to chemotherapy in hepatoblastoma (Hbs) is limited,
      and so is information about distinct patterns of p27 gene expression. Twenty-nine
      hepatoblastomas were evaluated for possible prognostic correlation between p27
      expression in different histotypes of hepatoblastoma, changes during
      chemotherapy, and outcome. These observations should prompt prospective
      randomized studies designed to investigate the predictive role of p27 expression
      in different Hbs histotypes. Patients were treated according to the Children's
      Cancer Group and Pediatric Oncology Group protocols, which included initial
      surgery before chemotherapy wherever possible. Follow-up ranged from 1 to 133
      months. The results show that primary well-differentiated fetal tumors without
      mitotic activity are strongly p27 positive. The embryonal pattern displays a
      variable p27 protein expression pattern, with focal positivity between completely
      negative zones; p27 is positive where the mitotic activity is low or absent and
      negative where the mitogenic activity is high. The vast majority of small
      undifferentiated cell components are p27 negative. p27 protein expression is
      downregulated after chemotherapy in the remaining fetal well-differentiated
      component of Hbs. Although this may imply selection of a more aggressive clone,
      all patients with this histology were cured in this series. Aggressiveness and
      ultimate prognosis for incompletely resected tumors after chemotherapy remain
      indeterminate.

PMID- 11957147
TI  - Cyclooxygenase-2 expression in endometrial cancer: correlation with microvessel
      count and expression of vascular endothelial growth factor and thymidine
      phosphorylase.
AB  - Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers,
      regulates angiogenesis by inducing production of angiogenic factors. These
      mechanisms require clarification in endometrial cancer. COX-2 expression was
      examined by immunohistochemistry and reverse-transcription polymerase chain
      reaction (RT-PCR) in endometrial cancer, endometrial hyperplasia, and normal
      endometrium in various phases. We investigated the relationship between COX-2
      expression and clinicopathologic variables, microvessel count, and expression of
      vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP).
      Immunohistochemistry demonstrated COX-2 protein in cancerous epithelial cells but
      not in stromal cells. COX-2 expression in epithelial cells was significantly
      greater in endometrial cancer (n = 63) and endometrial hyperplasia (n = 6) than
      in normal endometrium in any phase (n = 53). Although COX-2 did not correlate
      with any conventional clinicopathologic factor in patients with endometrial
      cancer, COX-2 expression was associated with high microvessel count, VEGF
      expression, and TP expression. By combined analysis of COX-2, VEGF, and TP,
      tumors with high expression of at least one factor had a significantly higher
      microvessel count than tumors expressing little of the three factors. We
      confirmed upregulation of COX-2 mRNA expression by RT-PCR in endometrial cancer
      (n = 17) compared to normal endometrium (n = 12). COX-2 mRNA expression
      significantly correlated with VEGF mRNA expression in these tumors. COX-2 is
      upregulated in endometrial cancer and facilitates tumor growth via angiogenesis
      produced in associated with VEGF and TP. Specific inhibition of COX-2 may be a
      useful therapeutic intervention in endometrial cancer.

PMID- 11957146
TI  - CTNNB1 mutations and beta-catenin expression in endometrial carcinomas.
AB  - Mutations in the beta-catenin gene (CTNNB 1) with abnormal nuclear accumulation
      of beta-catenin have recently been identified in endometrial carcinoma (EC).
      Their relationship with microsatellite instability (MI) is unclear. It has been
      suggested that matrix metalloproteinase-7 (MMP-7) and cyclin D1 (cD) genes are
      targets for beta-catenin activation. DNA from 73 patients with EC was obtained
      from tumor and normal tissue (59 endometrioid and 14 nonendometrioid). CTNNB 1
      mutations in exon 3 were assessed by single-strand conformation polymorphism and
      DNA sequencing. The results were correlated with immunostaining for beta-catenin,
      MMP-7, and cD. Three (CA)n repeats and mononucleotide tracts BAT 25 and BAT 26
      had been previously used for MI analysis. CTNNB1 mutations were identified in 15
      ECs (20.5%), all of them endometrioid carcinomas (15 of 59; 25.4%). They occurred
      in 6 of 19 MI-positive ECs (31.5%) and in 9 of 54 MI-negative ECs (16.6%). Eleven
      of the 15 CTNNB 1-mutated ECs showed beta-catenin nuclear immunostaining (P
      <.05). MMP-7 expression (>50% cells) was observed in 23 ECs, with 7 of these
      showing CTNNB 1 mutations. Significant expression of cD (>50% cells) was detected
      in 8 ECs, with 5 of these exhibiting CTNNB 1 mutations (P <.05). The results
      confirm that beta-catenin plays a role in endometrial carcinogenesis,
      particularly in endometrioid carcinomas. The results also suggest that MMP-7 and
      particularly cD may be targets of beta-catenin activation in ECs.

PMID- 11957148
TI  - Relationship between platelet-derived growth factor expression in leiomyomas and
      uterine volume changes after gonadotropin-releasing hormone agonist treatment.
AB  - The unopposed estrogen effect is the main cause of leiomyoma growth and is at the
      basis of the clinical use of gonadotropin-releasing hormone (GnRH) agonists.
      Platelet-derived growth factor (PDGF) has been indicated as the main growth
      factor involved, in vitro in the proliferation response of leiomyoma smooth
      muscle cells to estrogen stimulation. The aim of this article is to evaluate the
      mitogenic action of PDGF in vivo by studying the relationship between PDGF
      expression in leiomyomas and post-GnRH analogue treatment changes in uterine
      volume. Thirty-nine patients suffering from uterine leiomyomas were treated with
      leuprorelin acetate depot 3.75 mg for three cycles; 31 untreated patients were
      enrolled as control group. Uterine volume was determined twice by ultrasonography
      in each patient, the first time at admission and the second time after treatment
      in the study group and after 3 months in the control group. The change in the
      uterine volume was then evaluated. Patients underwent surgery, and PDGF
      immunohistochemical detection was performed on the obtained fibroid samples.
      Uterine volume decreased significantly after treatment, whereas just a poor
      modification was found in the controls. The decrease in the uterine volume was
      found to be statistically related to PDGF expression. Thus PDGF levels decreased
      in treated patients as compared with controls. The decreased PDGF production in
      leiomyomas after GnRH analogue treatment and the relationship between decreased
      PDGF expression and greater shrink age in uterine volume suggest that PDGF might
      have a mitogenic action on leiomyomas in vivo.

PMID- 11957149
TI  - MAGE antigen expression in monophasic and biphasic synovial sarcoma.
AB  - Synovial sarcomas are high-grade malignant mesenchymal tumors carrying a
      pathognomonic cytogenetic alteration t(X;18) involving the SYT gene on chromosome
      18 and either SSX1 or SSX2 on chromosome X. Morphologically, biphasic (BSS) and
      monophasic (MSS) variants can be distinguished. Cancer/testis (CT) antigens are
      expressed in a variety of malignant tumors, but not in normal tissues except in
      germ cells, primarily of the testis. Anti-MAGE monoclonal antibody (mAb) 57B
      previously showed a high incidence and homogenous reactivity pattern in a
      preliminary analysis of synovial sarcomas. This study was performed to analyze
      the expression of MAGE by immunohistochemistry with mAb 57B in 25 synovial
      sarcomas (12 monophasic, 13 biphasic), which were typed for the t(X;18)-derived
      fusion transcript by reverse transcriptase polymerase chain reaction (19 SYT
      SSX1, 6 SYT-SSX2). 57B immunoreactivity was present in 22 of 25 (88%) cases, and
      antigen expression was homogeneous in 14 of 22 57B-positive cases. Both
      morphological variants and both translocation types were immunoreactive; three
      SYT-SSX1 tumors (one MSS, two BSS) were 57B negative. Our study demonstrates that
      MAGE is frequently and homogeneously expressed in synovial sarcomas of both
      morphological variants and both translocation types, making these tumors an
      attractive target for MAGE antigen-based immunotherapy.

PMID- 11957151
TI  - Villous adenoma of the urinary tract: a lesion frequently associated with
      malignancy.
AB  - Villous adenomas arising in the urinary tract are rare. We identified 18 cases of
      villous adenomas of the bladder, urachus, and prostatic urethra. Patients ranged
      in age from 53 to 93 years with an average age of 69.6 years and a male
      preponderance of 67%. In six cases (33%), the lesion was pure villous adenoma. In
      three cases (17%), there was villous adenoma with in situ adenocarcinoma. In six
      cases (33%) there was villous adenoma with in situ and infiltrating
      adenocarcinoma. One case (6%) had villous adenomas with in situ (noninvasive)
      papillary urothelial carcinoma. One case (6%) had villous adenomas with in situ
      adenocarcinoma and in situ papillary (noninvasive) and infiltrating urothelial
      carcinoma. The remaining case (6%) had villous adenoma with in situ and
      infiltrating adenocarcinoma and in situ (noninvasive) papillary and infiltrating
      urothelial carcinoma. Clinical outcome was available in eight of the cases, with
      a mean follow-up of 4.6 years. No evidence of recurrence was found in two
      patients with pure villous adenoma or in two patients with villous adenoma and
      only in situ adenocarcinoma, all of whom were treated by nonradical excision.
      However, two of three cases with infiltrating cancer developed distant metastases
      despite radical surgery; the remaining patient was disease-free 11 years after
      transurethral resection. The case with villous adenoma and in situ urothelial
      carcinoma progressed to sarcomatoid urothelial carcinoma following partial
      cystectomy. Eight of 10 villous adenomas cases studied expressed the epitope for
      mAbDas1, found on colonic epithelium and primary adenocarcinomas of the bladder
      and urachus but not on normal or neoplastic urothelium. This study expands the
      spectrum of histologic features accompanying villous adenomas of the urinary
      tract. Coexisting infiltrating adenocarcinoma is often present, necessitating
      thorough sampling of any lesion diagnosed by biopsy as villous adenoma. Pure
      villous adenoma and those well-sampled lesions also containing in situ
      adenocarcinoma portend a favorable prognosis, even without radical treatment.
      Coexisting in situ or infiltrating carcinoma suggests a more aggressive course.
      Histologically, immunohistochemically, and prognostically, these lesions appear
      analogous to their counterparts in the intestine.

PMID- 11957150
TI  - Proliferative activity of renal cell carcinoma associated with acquired cystic
      disease of the kidney: comparison with typical renal cell carcinoma.
AB  - To assess the proliferative activity of renal cell carcinoma (RCC-A) in patients
      with acquired cystic disease of the kidney (ACDK) after long-term hemodialysis,
      we analyzed cell cycle, DNA ploidy, and S-phase fraction by flow cytometry (FCM)
      and proliferating cell nuclear antigen (PCNA) labeling index by
      immunohistochemistry. The data were compared with those of typical RCC (tRCC).
      Sixteen (88.9%) of 18 RCC-As showed a diploid pattern. The values of cells at
      each phase in the cell cycle in RCC-A group (S, 4.36% + 2.16%; G2M, 5.06% +
      1.90%; S+G2M, 9.41% + 2.81%; P <.05) were significantly different from those of
      tRCCs (S, 8.91% + 6.58%; G2M, 8.77% + 5.73%; S+G2M; 17.67% + 7.61%). The PCNA
      labeling index was statistically significantly lower in the RCC-As (24.01% +/-
      13.4%; P <.05) than in tRCCs (42.27% +/- 26.1%). These results indicate that the
      RCC-As are less proliferative than tRCC and are consistent with the observation
      that RCC-As are less aggressive neoplasms.

PMID- 11957152
TI  - Diagnosing minimal adenocarcinoma on prostate needle biopsy by real-time dynamic
      telepathology through the internet: evaluation of an economic technology for
      remote consultation.
AB  - Computer-aided telepathology was introduced about 10 years ago, but has not yet
      met with worldwide acceptance. Recently, the internet has been used for image
      transmission in telepathology. We set up an easily assembled system comprising a
      common microscope, a charge-coupled device (CCD) camera, a personal computer, and
      a commercial internet surveillance program with internet accessibility. The
      consultant then views the real-time images using a common web browser at the
      remote site. The purpose of the study was to assess the ability of the system to
      transmit images of sufficient quality to achieve high concordance between the
      diagnoses made at the home base and at the remote site. We chose cases of minimal
      adenocarcinoma on prostate needle biopsy, because these lesions are liable to be
      overlooked and, even if discovered, are subject to differences in interpretation
      due to their limited size and subtle histologic changes. One hundred prostate
      needle biopsy specimens, including 45 minimal adenocarcinoma, 11 atypical small
      acinar proliferation, and 44 benign lesions, were tested. Two pathologists,
      unaware of the final diagnoses, were recruited to provide intra- and
      interinstitutional consultation. The overall concordance rates between
      telepathology diagnoses and final diagnoses were 97% and 94% for the two
      pathologists, respectively. Our results demonstrate that this method is effective
      for teleconsultation. Similar systems using the internet can be easily set up by
      ordinary pathology laboratories to facilitate remote consultation.

PMID- 11957153
TI  - Depletion of mitochondrial DNA in the liver of an infant with neonatal giant cell
      hepatitis.
AB  - A boy presented with lactic acidosis, hepatomegaly, hypoglycemia, generalised
      icterus, and muscle hypotonia in the first weeks of life. At the age of 2 months,
      neonatal giant cell hepatitis was diagnosed by light microscopy. Electron
      microscopy of the liver revealed an accumulation of abnormal mitochondria and
      steatosis. Skeletal muscle was normal on both light and electron microscopy. At
      the age of 5 months, the patient died of liver failure. Biochemical studies of
      the respiratory chain enzymes in muscle showed that cytochrome-c oxidase (complex
      IV) and succinate-cytochrome-c oxidoreductase (complex II + III) activities were
      (just) below the control range. When related to citrate synthase activity,
      however, complex IV and complex II + III activities were normal. Complex I
      activity was within the control range. The content of mitochondrial DNA (mtDNA)
      was severely reduced in the liver (17% to 18% of control values).
      Ultracytochemistry and immunocytochemistry of cytochrome-c oxidase demonstrated a
      mosaic pattern of normal and defective liver cells. In defective cells, a reduced
      amount of the mtDNA-encoded subunits II-III and the nuclear DNA-encoded subunits
      Vab was found. Cells of the biliary system were spared. Immunohistochemistry of
      mtDNA replication factors revealed normal expression of DNA polymerase gamma. The
      mitochondrial single-stranded binding protein (mtSSB) was absent in some abnormal
      hepatocytes, whereas the mitochondrial transcription factor A (mtTFA) was
      deficient in all abnormal hepatocytes. In conclusion, depletion of mtDNA may
      present as giant cell hepatitis. mtTFA and to a lesser degree mtSSB are reduced
      in mtDNA depletion of the liver and may, therefore, be of pathogenetic
      importance. The primary defect, however, is still unknown.

PMID- 11957154
TI  - Hepatosplenic gammadelta-T-cell lymphoma with leukemic course after renal
      transplantation.
AB  - Hepatosplenic gammadelta-T-cell lymphoma (HSTCL) is a rare extranodal T-cell non
      Hodgkin's lymphoma (T-NHL) with only 46 well-documented cases in medical
      literature. Notably, a relatively high number of these case reports (15%)
      describe the occurrence of HSTCL after solid organ transplantation. We describe
      the case of a 45-year-old man who developed a leukemic HSTCL 5 years after renal
      transplantation and continous immunosuppression with cyclosporine A and
      prednisolone. After a rapid clinical course, the patient died and autopsy was
      performed. The malignant lymphocytes showed a natural killer-like gammadelta-T
      cell phenotype (CD2(+), CD3(+), CD7(+), TCR gammadelta(+), CD56(+), TIA-1(+),
      CD4(-), CD8(-), and TCR alphabeta(-)) and infiltrated the sinusoids of liver and
      the red pulp of the spleen. Cytogenetically, an isochromosome 7q, trisomy 8, Y
      loss, and a translocation t(1;4) was detectable. This case shows the difficulties
      of recognizing HSTCL early in the clinical course and underlines that all types
      of T-NHL, nodal as well as extranodal, have to be considered in the differential
      diagnosis of posttransplantation lymphoproliferative disorders. Moreover, HSTCL
      seems to occur as a specific late complication of solid organ transplantation.

PMID- 11957155
TI  - Pathology manpower.

PMID- 11957159
TI  - Venial and mortal sins: the problems of confounding and bias.

PMID- 11957160
TI  - Earlier recovery with beating-heart surgery: a comparison of 300 patients
      undergoing conventional versus off-pump coronary artery bypass graft surgery.
AB  - OBJECTIVE: To compare outcomes and cost of off-pump coronary artery bypass (OP
      CAB) surgery versus cardiopulmonary bypass-assisted coronary artery bypass graft
      (CABG) surgery. DESIGN: Retrospective review. SETTING: A tertiary care university
      teaching hospital. PARTICIPANTS: Patients (n = 300) undergoing isolated CABG
      surgery performed by a single surgeon between July 1998 and February 2000.
      INTERVENTIONS: Two groups of patients were compared: 150 consecutive patients
      undergoing OP-CAB surgery and a matched cohort of 150 consecutive patients
      undergoing conventional CABG surgery. MEASUREMENTS AND MAIN RESULTS: The 2 groups
      were evenly matched in terms of age and incidence of diabetes, hypertension,
      peripheral vascular disease, left main disease, prior strokes, congestive heart
      failure, and recent infarctions. OP-CAB procedures required 3.3 grafts per
      patient versus 3.8 grafts per patient required for CABG surgery (p = 0.02).
      Overall mortality was 2.0% (1.3% in the OP-CAB surgery group v 2.7 % in the CABG
      surgery group; p = NS). Extubation times (6.6 hours v 9.5 hours; p = 0.003),
      surgical intensive care unit length of stay (39 hours v 49 hours; p = 0.03), and
      hospital length of stay (6.1 days v 7.0 days; p = 0.04) were all significantly
      shorter for the OP-CAB surgery group. The combined aggregate endpoints of death
      and major morbidity were significantly less in the OP-CAB surgery group (5.3% v
      12.7%; p = 0.02). CONCLUSION: OP-CAB surgery is associated with low morbidity and
      mortality and accelerated recovery compared with conventional CABG surgery. OP
      CAB surgery may represent the ideal revascularization strategy for patients at
      high risk for undergoing cardiopulmonary bypass.

PMID- 11957161
TI  - Postoperative atrial fibrillation: a comparison of off-pump coronary artery
      bypass surgery and conventional coronary artery bypass graft surgery.
AB  - OBJECTIVE: To compare the incidence and pattern of onset of postoperative atrial
      fibrillation (AF) in patients undergoing coronary artery bypass graft (CABG)
      surgery with and without cardiopulmonary bypass (CPB). DESIGN: Retrospective,
      cohort-controlled study. SETTING: University hospital and tertiary referral
      center. PARTICIPANTS: A group of 108 consecutive patients who underwent primary
      off-pump coronary artery bypass (OP-CAB) surgery and a control group of 100
      patients who underwent CABG surgery with CPB. All patients underwent surgery
      between January and September 1999. INTERVENTIONS: Patients in the OP-CAB surgery
      group were operated on by either of 2 surgeons. The CABG surgery group was drawn
      from the general pool of patients operated on by 1 of 10 surgeons. All patients
      underwent median sternotomy and received standard anesthesia and intensive care
      unit management for this institution. MEASUREMENTS AND MAIN RESULTS: Data from 99
      OP-CAB surgery patients (data incomplete in 9 patients) were compared with data
      from 100 CABG surgery patients. General demographics were similar except the CABG
      surgery group received a higher mean number of distal anastomoses (3.3 v 3.0; p =
      0.028) The incidence of AF was similar in both groups (OP-CAB surgery, 25% v CABG
      surgery, 18%; p = 0.228). The peak incidence of AF was postoperative day 2 in
      both groups. The median hospital length of stay was increased in patients
      developing AF. CONCLUSION: Avoiding CPB does not seem to reduce the incidence of
      postoperative AF in CABG surgery. The similar time distribution of onset of AF in
      OP-CAB surgery patients and CABG surgery patients may point toward a common
      cause.

PMID- 11957162
TI  - Practice pattern variability for myocardial revascularization: impact on resource
      use across 24 centers.
AB  - OBJECTIVE: To determine the predictors of hospital length of stay (LOS) after
      elective uncomplicated coronary artery bypass graft surgery. DESIGN:
      Retrospective analysis of the EPI-1 database, 1991-1993. SETTING: Multicenter; 24
      academic, private, federal, and health maintenance institutions. PARTICIPANTS:
      Patients undergoing elective CABG surgery (n = 2,417). MEASUREMENTS AND MAIN
      RESULTS: Using a systematic sampling scheme at each site, each patient was
      evaluated to identify markers of chronic disease, perioperative test data,
      treatments, adverse outcomes, and LOS. Institutional differences in the care of
      patients free of complications were assessed using a multivariate model. LOS was
      the outcome variable selected to estimate cost. A total of 861 patients (37%)
      were free of any complication. The mean site LOS ranged from 5.4 to 9.0 days,
      with half of the 24 centers reporting a hospital LOS routinely >7.1 days. The
      predominant factor associated with a complication-free LOS was site per se,
      accounting for 32% of the variability in hospital LOS that could not be explained
      by any site characteristic (eg, size, geographic location, academic affiliation).
      Multivariable analysis identified 3 demographic predictors--age >75 years
      (increasing LOS by 1.3 days), admission from the emergency department (increasing
      LOS by 0.7 days), and uninsured or Medicaid-insured (increasing LOS by 0.4 days);
      2 historical predictors--New York Heart Association class III or IV congestive
      heart failure (increasing LOS by 0.5 days) and history of arrhythmia (increasing
      LOS by 0.7 days); and 2 practice patterns--transfusion of blood products
      (increasing LOS by 0.3 days) and delayed extubation (increasing LOS by 0.5 days).
      Previous myocardial infarction, diabetes, chronic obstructive pulmonary disease,
      neurologic disease, and other historical factors were not associated with LOS in
      patients without a complication. CONCLUSION: A substantial variability in LOS
      after complication-free coronary artery bypass graft surgery was determined
      predominantly by site per se, even after adjustment for disease severity, site
      type or location, and surgical and anesthetic practices. The variability in LOS
      was likely due to practice style influences and represents an opportunity to
      decrease waste in the provision of a common and expensive procedure.

PMID- 11957163
TI  - Alfentanil and sufentanil in fast-track anesthesia for coronary artery bypass
      graft surgery.
AB  - OBJECTIVE: To evaluate alfentanil, sufentanil, and the combination of both
      opioids in patients undergoing cardiac surgery. DESIGN: Prospective, randomized
      study. SETTING: University hospital. PARTICIPANTS: Patients undergoing coronary
      artery bypass graft (CABG) surgery (n = 195), randomly assigned to 3 groups of 65
      each. INTERVENTIONS: Patients in group A received alfentanil, induction (15
      microg/kg) and maintenance (15 microg/kg/hr); patients in group S received
      sufentanil, induction (1 microg/kg) and maintenance (1 microg/kg/h); and patients
      in group AS received alfentanil and sufentanil, induction with alfentanil (15
      microg/kg) and maintenance with sufentanil (1 microg/kg/hr). MEASUREMENTS AND
      MAIN RESULTS: Hemodynamic data showed a reduction of all parameters at induction
      in the 3 groups (p < 0.05). Cardiac index decreased at induction in all groups (p
      < 0.05) but increased in groups S and AS toward baseline values at the end of
      surgery. The intubation time and length of stay in the intensive care unit were
      less in group AS (2.3 +/- 1.2 hours; p < 0.001 and 20 +/- 8 hours; p < 0.05),
      than in groups A (4.2 +/- 1.7 hours and 28 +/- 13 hours) and S (3.1 +/- 1.1
      hours; p < 0.05 and 26 +/- 12 hours). Length of hospital stay and patients'
      outcome were similar in the 3 groups. CONCLUSION: Although the differences among
      groups regarding extubation time, intensive care unit length of stay, and some
      hemodynamic data were statistically significant, the differences were clinically
      small. All 3 anesthetic protocols were shown to be safe and appropriate for
      patients undergoing elective coronary artery bypass graft surgery and early
      postoperative tracheal extubation.

PMID- 11957165
TI  - The effect of cardiopulmonary bypass and inspired oxygen concentration on left
      ventricular contrast opacification with optison, a second-generation ultrasound
      contrast agent.
AB  - OBJECTIVE: To investigate the influence of cardiopulmonary bypass (CPB) and
      fraction of inspired oxygen (F(I)O(2)) on the contrast effect of Optison, a
      second-generation ultrasound contrast agent, in humans during coronary artery
      bypass graft (CABG) surgery with transesophageal echocardiography (TEE). DESIGN:
      Prospective, observational, repeated-measures design. SETTING: A single
      university hospital. PARTICIPANTS: Ten patients who underwent elective CABG
      surgery. INTERVENTIONS: A transgastric, midpapillary, short-axis view of the left
      ventricle was obtained with TEE in the conventional imaging mode. A central
      injection of 0.3 mL of Optison was administered at 4 stages: after induction of
      anesthesia at F(I)O(2) = 1.0 and F(I)O(2) = 0.43 +/- 0.02 and after protamine
      administration at F(I)O(2) = 1.0 and F(I)O(2) = 0.52 +/- 0.09. Background
      corrected maximal pixel intensity (PImax(corr)) in the left ventricle was
      determined with videodensitometry. To estimate the magnitude of change in pixel
      intensities, point estimates of differences in PImax(corr) and their 95% and 99%
      confidence intervals were calculated after repeated measures analysis of
      variance. MEASUREMENTS AND MAIN RESULTS: Decreasing the F(I)O(2) from 1.0 to <1
      did not alter PImax(corr) significantly before or after CPB (mean change = -4.2
      and 0.8; SE = 2.0 and 1.9; p = 0.06 and 0.68). Values for PImax(corr) before and
      after CPB were not significantly different at either F(I)O(2) = 1.0 or F(I)O(2)
      <1 (mean change = -3.3 and 1.7; SE = 2.4 and 2.7; p = 0.26 and 0.54). Mean
      differences from initial values ranged from a 10% decrease to a 5% increase.
      CONCLUSION: In patients who undergo CABG surgery, the contrast opacification of
      Optison in the left ventricle is not changed by CPB or alterations in F(I)O(2)
      during intraoperative TEE. The application of Optison for enhancement of the
      endocardial border is not limited during cardiac surgery.

PMID- 11957164
TI  - Glucocorticoid effects on the inflammatory and clinical responses to cardiac
      surgery.
AB  - OBJECTIVE: To measure the effects of glucocorticoids on the systemic inflammatory
      response and clinical recovery after cardiac surgery. DESIGN: Randomized,
      prospective, double-blind, placebo-controlled clinical trial with concurrent
      comparison groups. SETTING: University medical center. PARTICIPANTS: Patients
      scheduled for elective coronary artery bypass graft surgery using normothermic
      cardiopulmonary bypass (CPB) and a standardized anesthetic. INTERVENTIONS:
      Participants randomly received either methylprednisolone, 15 mg/kg intravenously
      1 hour before surgery and 0.3 mg/kg intravenously every 6 hours x 4 doses, or
      placebo. Comparison groups included cardiac surgical patients who received
      etomidate to lower endogenous cortisol during surgery and healthy volunteers who
      received methylprednisolone only. MEASUREMENTS AND MAIN RESULTS: Patients who
      received methylprednisolone had a significant reduction in circulating
      interleukin (IL)-6 at 60 minutes after CPB (p < 0.05) and on the morning of the
      1st (p < 0.01) and 3rd (p < 0.05) postoperative days and a significant increase
      in circulating IL-10 at 60 minutes after CPB (p < 0.01) compared with the placebo
      group. Etomidate, given to lower cortisol during surgery, was associated with
      significantly decreased IL-6 and IL-10 responses to surgery compared with the
      placebo group, whereas methylprednisolone alone, given to healthy nonsurgical
      volunteers, had no effect on these cytokines. After adjusting for age, there were
      no significant differences in postoperative length of hospital stay between the
      methylprednisolone-treated (4.6 days) and placebo (6.1 days) groups or in the
      duration of mechanical ventilation (9.9 hours and 15.6 hours). No patient treated
      with methylprednisolone had nausea and vomiting on the 1st postoperative day
      compared with 33% of placebo-treated patients (p = 0.02). Glucose was
      significantly higher after methylprednisolone treatment at 1 hour after CPB (276
      mg/dL v 210 mg/dL; p = 0.001) and at 2 hours (289 mg/dL v 213 mg/dL; p = 0.009)
      and 8 hours (247 mg/dL v 196 mg/dL; p = 0.02) after surgery. There were no
      differences in pain scores and no significant intergroup differences in lung peak
      expiratory flow rate or alveolar-arterial oxygen gradients after surgery.
      CONCLUSION: This study shows significant effects of glucocorticoids on the
      production of IL-6 and IL-10 in response to cardiac surgery but only minor
      effects on clinical recovery.

PMID- 11957166
TI  - Considerations in patients undergoing implantation of a biventricular pacemaker.
AB  - OBJECTIVE: To compare hemodynamics and oxygenation in patients with congestive
      heart failure and broad QRS complexes before and with biventricular DDD pacing
      and to report experience with this new procedure. DESIGN: Prospective,
      observational study. SETTING: Major university-affiliated community hospital.
      PARTICIPANTS: Ten patients with congestive heart failure (New York Heart
      Association III to IV) and broad QRS complexes (>160 msec). INTERVENTIONS:
      Patients underwent implantation of a biventricular pacemaker (n = 4) or
      implantation of a combined biventricular pacemaker and cardioverter-defibrillator
      (n = 6). Anesthesia was performed using remifentanil (0.2 to 0.3 microg/kg/min)
      and propofol. Propofol was used as target-controlled infusion (plasma target
      concentration, 1.5 to 2.5 microg/mL). MEASUREMENTS AND MAIN RESULTS: Hemodynamics
      and oxygenation were measured before and with biventricular DDD pacing. Mean
      arterial pressure was significantly increased from 64.7 +/- 5.8 mmHg to 77.8 +/-
      10.6 mmHg by biventricular pacing, whereas cardiac index (2.2 +/- 0.3 L/min/m(2)
      before and 2.3 +/- 0.3 L/min/m(2) with biventricular pacing) and pulmonary
      capillary wedge pressure (12.1 +/- 3.8 mmHg before and 14.2 +/- 3.6 mmHg with
      biventricular pacing) remained unchanged. Left ventricular stroke work index was
      increased >10% in 7 patients. Oxygen delivery, oxygen consumption, and difference
      in arteriovenous oxygen concentration were not affected. Anesthesia with
      remifentanil and propofol was safe and well-controllable and allowed immediate
      extubation at the end of the operation. CONCLUSION: There was no acute
      intraoperative improvement of hemodynamics except increased mean arterial
      pressure with biventricular pacing. Left ventricular performance seemed to
      improve with biventricular pacing in some patients. These results might be due to
      a nonoptimized atrioventricular delay. Postoperatively, atrioventricular delay
      was individually programmed for each patient by Doppler transmitral flow
      patterns.

PMID- 11957167
TI  - Cardiovascular responses to repetitive defibrillation during implantable
      cardioverter-defibrillator testing.
AB  - OBJECTIVE: To study the effects of electrical applications and subsequent
      postshock hypotension on myocardial performance and vascular tone during
      implantable cardioverter-defibrillator (ICD) placement. DESIGN: Prospective,
      blinded, observational investigation. SETTING: Single, university-affiliated
      institution. PARTICIPANTS: Twenty patients undergoing elective ICD placement and
      testing under general anesthesia. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Serial measurements were made of hemodynamic variables, left ventricular
      end-systolic (ESA) and end-diastolic (EDA) areas, fractional-area-of-contraction
      (FAC), time of hypoperfusion (when mean arterial pressure < or =50 mmHg
      postshock), and applied conversion energy. Multiple linear regression was
      performed to determine correlations among collected variables, and repeated
      measures analysis of variance was used to compare mean values. Minimal changes
      were detected in mean values of arterial, pulmonary, and central venous
      pressures; cardiac output; heart rate; and mixed venous saturation during
      repeated testing. Percentage changes in cardiac index (CI) rose and systemic
      vascular resistance index (SVRI) fell, however, as the number of shocks
      increased, reaching significance at the seventh and eighth shocks (v baseline;
      both p = 0.015). The percentage change in CI was linearly related to
      hypoperfusion time and accumulated energy (%deltaCI = 1.553 + [0.068 x sigma
      hypoperfusion time [sec]], r = 0.92, p < 0.001; %deltaCI = 0.326 + [0.125 x sigma
      Energy [J]], r = 0.94, p < 0.001). The percentage change in SVRI was inversely
      related to hypoperfusion time and accumulated energy (%deltaSVRI = 2.195 - [0.122
      x sigma energy [J]], r = 0.79, p = 0.004; %deltaSVRI = 0.542 - [0.0634 - sigma
      hypoperfusion time [sec]], r = 0.73, p = 0.01). Echocardiographic EDA, ESA, and
      FAC were not significantly changed but showed substantial variability.
      CONCLUSION: Hemodynamic stability was generally well maintained during ICD
      placement and testing. Increases in CI were associated with concurrent reductions
      in systemic afterload, rather than enhanced FAC. Increasing postshock hypotension
      and applied energy were associated with decreases in CI and systemic afterload.
      Insignificant, but highly variable, changes were noted echocardiographically.

PMID- 11957168
TI  - Comparison of continuous, stat, and intermittent cardiac output measurements in
      patients undergoing minimally invasive direct coronary artery bypass surgery.
AB  - OBJECTIVE: To compare intermittent cardiac output (ICO) with continuous cardiac
      output (CCO) and stat cardiac output (SCO) measurements in patients undergoing
      minimally invasive direct coronary artery bypass (MIDCAB) surgery. DESIGN:
      Prospective, clinical study. SETTING: Single, tertiary referral center.
      PARTICIPANTS: Twenty adult patients undergoing off-pump MIDCAB surgery from
      January through June 2000. INTERVENTIONS: Each patient had a 7.5F 5-lumen
      pulmonary artery thermodilution catheter (CCO catheter, Baxter Healthcare
      Corporation, Irvine, CA) inserted for measurement of cardiac output (CO). ICO,
      CCO, and SCO were compared at 10 predefined time points. RESULTS: A total of 400
      data pairs for CO were obtained. ICO values ranged from 1.8 to 8.4 L/min; CCO,
      1.9 to 7.5 L/min; and SCO, 2.25 to 6.35 L/min. Correlation between ICO and CCO
      was significant (correlation coefficient, r = 0.78, p < 0.001), accompanied by a
      bias of -0.095 L/min and precision of 0.729 L/min. Similarly, the correlation
      between ICO and SCO was significant (r = 0.79, p < 0.001), accompanied by good
      accuracy (bias, 0.084 L/min) and precision (0.843 L/min). There were
      statistically significant decreases in mean arterial pressure, CO, cardiac index,
      stroke volume, stroke volume index, and left and right ventricular stroke work
      indices during anastomosis of the left internal mammary artery to left anterior
      descending artery. These parameters returned to baseline preinduction values 1
      minute after completion of the anastomosis. CONCLUSION: Excellent correlation,
      accuracy, and precision were found among the 3 methods of measuring CO in
      patients undergoing MIDCAB surgery. Further studies are needed to assess their
      accuracy in multivessel off-pump coronary artery bypass graft surgery and in
      patients with poor left ventricular function.

PMID- 11957169
TI  - Intrathoracic blood volume index measured by thermodilution for preload
      monitoring after cardiac surgery.
AB  - OBJECTIVE: To investigate the accuracy of measurement of intrathoracic blood
      volume index by single thermodilution (ITBVI*) and its sensitivity to detect
      changes in preload after cardiac surgery compared with conventional
      transpulmonary arterial dye dilution ITBVI and with conventional monitoring
      (central venous pressure [CVP] and left ventricular end-diastolic area index
      [EDAI] by transesophageal echocardiography). DESIGN: Prospective clinical study.
      SETTING: University hospital. PARTICIPANTS: Nineteen patients immediately after
      cardiac surgery. INTERVENTIONS: Volume loading was administered with 20 mL of
      oxypoligelatine (Haemaccel [Behringwerke Aktiengesellschaft Corp, Marburg,
      Germany]) 3.5% times body mass index over 10 minutes. MEASUREMENTS AND MAIN
      RESULTS: Intrathoracic blood volume index was measured by dye dilution (ITBVI)
      and thermodilution (ITBVI*) immediately before and after volume loading.
      Measurements of ITBVI and ITBVI* correlated closely (r = 0.94; p < 0.0001). With
      volume loading, ITBVI and ITBVI* increased significantly from 877 +/- 195 mL/m(2)
      to 967 +/- 180 mL/m(2) and from 889 +/- 195 mL/m(2) to 954 +/- 185 mL/m(2).
      Percent changes in ITBVI (deltaITBVI) and ITBVI* (deltaITBVI*) did not differ
      significantly and correlated closely (r = 0.90; p < 0.0001). Percent changes in
      cardiac index (CI) as a result of volume loading (deltaCI) revealed significant
      correlation to deltaITBVI (r = 0.85; p < 0.0001) and to deltaITBVI* (r = 0.76; p
      < 0.0005). No significant correlation could be found between deltaCI and
      deltaEDAI or deltaCVP. CONCLUSION: In patients undergoing cardiac surgery,
      determination of ITBVI* revealed close agreement with measurements derived by
      ITBVI. Enhancement in cardiac preload was adequately detected by ITBVI*.

PMID- 11957170
TI  - A cadaver study to measure the adult glottis and subglottis: defining a problem
      associated with the use of double-lumen tubes.
AB  - OBJECTIVE: To test the hypothesis that the adult cricoid diameter is the same or
      less than that of the glottis. DESIGN: Prospective. SETTING: A city mortuary.
      PARTICIPANTS: Adult cadavers undergoing autopsy. INTERVENTIONS: After removal of
      the organs, the trachea was opened above the first ring to allow access to the
      cricoid from below, and the cricothyroid membrane was cut so that passage of
      measuring sounds through the vocal cords from above could be confirmed.
      MEASUREMENTS AND MAIN RESULTS: In 79 male and 55 female cadavers, the largest of
      a graduated series of cylindrical sounds that the cricoid ring would accommodate
      was noted. Then the biggest size possible that could pass through the glottis was
      measured. Height and weight were recorded. In 68% of males and 76% of females,
      glottic diameter was greater than subglottic; in all other cases, it was the
      same. In none was it smaller. Correlation between height and cricoid diameter was
      0.24 for male cadavers and 0.21 for female cadavers. Regression analysis showed
      females to average a cricoid diameter 3.5 mm less than males of the same height.
      CONCLUSIONS: The ruling diameter of the adult larynx is not the glottis but the
      cricoid ring. Its correlation with height is extremely poor, and it averages 3.5
      mm less in females than males of the same height. These findings are important
      for thoracic anesthesiologists.

PMID- 11957171
TI  - Prediction of arterial oxygen tension during one-lung ventilation: analysis of
      preoperative and intraoperative variables.
AB  - OBJECTIVE: To determine whether currently available preoperative and
      intraoperative variables related to arterial oxygen tension (PaO(2)) can be used
      as predictors for low PaO(2) during one-lung ventilation (OLV). DESIGN: A
      prospective cohort study. SETTING: Primary university hospital. PARTICIPANTS:
      Adult patients (n = 92) undergoing thoracic surgery requiring OLV. INTERVENTIONS:
      Preoperative and intraoperative data, including past medical history, physical
      examination, and usual preoperative and intraoperative tests, were collected and
      used as explanatory variables for PaO(2) during OLV by univariate and
      multivariate analysis. A stepwise logistic regression including the same
      independent variables was used to identify patients who should be expected to
      develop arterial hypoxemia (PaO(2) <70 mmHg). Arterial blood gas samples were
      analyzed 15 minutes after the onset of OLV and after thoracotomy to determine the
      lowest PaO(2) value during OLV. MEASUREMENTS AND MAIN RESULTS: Preoperative (age,
      hematocrit, relative perfusion of the nondependent lung) and intraoperative
      (PaO(2) during 2-lung ventilation and mean arterial pressure at the lowest
      PaO(2)) variables were identified as independent factors affecting PaO(2) in OLV.
      PaO(2) during 2-lung ventilation was the only independent variable accounting for
      arterial hypoxemia when multivariate logistic regression was performed.
      CONCLUSION: The PaO(2) during OLV can be predicted using routinely available
      preoperative and intraoperative data. From a clinical point of view, this study
      failed to identify patients at risk of arterial hypoxemia when OLV is instituted
      because mainly intraoperative independent variables are involved in the decrease
      of PaO(2) in this situation.

PMID- 11957172
TI  - Cerebral oximetry provides early warning of oxygen delivery failure during
      cardiopulmonary bypass.

PMID- 11957173
TI  - Fistulized mycotic aneurysm of the aortic arch.

PMID- 11957174
TI  - Tetralogy of Fallot with total anomalous pulmonary venous connection:
      pathophysiology and management.

PMID- 11957175
TI  - Intrinsic airway abnormality in 2 patients with multiple congenital defects: a
      chance association or an unrecognized association.

PMID- 11957176
TI  - Endovascular aortic repair.

PMID- 11957177
TI  - The AbioCor artificial replacement heart: bioengineering meets bioethics.

PMID- 11957178
TI  - Case 2-2002. Thoracic epidural anesthesia in patients with ankylosing spondylitis
      undergoing coronary artery surgery.

PMID- 11957179
TI  - Pro: right-sided double-lumen endotracheal tubes should be routinely used in
      thoracic surgery.

PMID- 11957180
TI  - Con: right-sided double-lumen endotracheal tubes should not be routinely used in
      thoracic surgery.

PMID- 11957181
TI  - An unusual chest radiograph after pulmonary thromboendarterectomy.

PMID- 11957182
TI  - Unexpected small tracheobronchial tree size and separation of the lungs.

PMID- 11957184
TI  - Safe internal jugular vein cannulation.

PMID- 11957185
TI  - Intraoperative aprotinin use in arterial switch operations.

PMID- 11957186
TI  - The use of nitrogen and nitric oxide to control pulmonary blood flow in the
      Norwood operation.

PMID- 11957187
TI  - Introduction: severe chronic neutropenia.

PMID- 11957188
TI  - Neutropenia: causes and consequences.
AB  - Neutrophils play a critical role in the acute inflammatory response and host
      defenses against bacterial infections. Neutropenia, a deficiency of these cells,
      predisposes to infection, chiefly by organisms resident on body surfaces. The
      risk of infection is greatest with severe neutropenia, defined by an absolute
      blood neutrophil count (ANC) less than 0.5 x 10(9)/L. Severe chronic neutropenia,
      lasting for more than a few weeks, can be caused by congenital marrow defects, as
      well as intrinsic and acquired disorders. Evaluation of patients begins with
      confirmation of neutropenia and examination of a blood smear. A careful review of
      the patient's medical history, family history, and physical examination is
      extremely important. Most severely neutropenic patients have a history of oral
      ulcers and inflammation and recurrent skin infections. Examination of a bone
      marrow aspirate and/or biopsy and cytogenetic testing are primary for diagnostic
      evaluation.

PMID- 11957189
TI  - Kostmann syndrome and severe congenital neutropenia.
AB  - Congenital neutropenia (CN) includes hematologic disorders characterized by
      severe neutropenia with an absolute neutrophil count (ANC) below 0.5 x 10(9)/L
      associated with severe systemic bacterial infections from early infancy. One
      subtype of CN, Kostmann syndrome, was originally described as an autosomal
      recessive disorder, characterized by early-stage maturation arrest of
      myelopoiesis. Autosomal-dominant and sporadic cases have also been reported.
      Recent studies on the genetic bases of CN have detected different inherited or
      spontaneous point mutations in the neutrophil elastase gene. Development of
      additional genetic defects during the course of disease, such as granulocyte
      colony-stimulating factor (G-CSF)-receptor gene mutations and cytogenetic
      aberrations, indicates an underlying genetic instability. Data on more than 300
      patients with CN collected by the Severe Chronic Neutropenia International
      Registry (SCNIR) since 1994 demonstrate that, independent of the CN subtype, more
      than 90% of patients respond to recombinant human (rHu)G-CSF with ANCs that can
      be maintained at approximately 1.0 x 10(9)/L. Adverse events include mild
      splenomegaly, moderate thrombocytopenia, osteoporosis, and malignant
      transformation into myelodysplasia (MDS)/leukemia. If and how rHuG-CSF treatment
      impacts on these adverse events remains unclear since there are no historical
      controls for comparison. Hematopoietic stem cell transplantation (HSCT) is still
      the only available treatment for patients refractory to rHuG-CSF treatment.

PMID- 11957190
TI  - Cyclic neutropenia.
AB  - Cyclic neutropenia is a rare hematologic disorder, characterized by repetitive
      episodes of fever, mouth ulcers, and infections attributable to recurrent severe
      neutropenia. Fluctuations in blood cells are due to oscillatory production of
      cells by the bone marrow. Recent genetic, molecular, and cellular studies have
      shown that autosomal-dominant cyclic neutropenia and sporadic cases of this
      disease are due to a mutation in the gene for neutrophil elastase (ELA2), located
      at 19p13.3. This enzyme is synthesized in neutrophil precursors early in the
      process of primary granule formation. It is currently presumed that the mutant
      neutrophil elastase functions aberrantly within the cells to accelerate apoptosis
      of the precursors, resulting in effective and oscillatory production. Cyclic
      neutropenia is effectively treated with granulocyte colony-stimulating factor (G
      CSF), usually at doses of 1 to 5 microg/kg/d (median dose, 2.5 microg/kg/d). Long
      term, daily, or alternate-day administration reduces fever, mouth ulcers, and
      other inflammatory events associated with this disorder. Leukemic transformation
      is not a recognized risk for cyclic neutropenia, with or without treatment with G
      CSF.

PMID- 11957191
TI  - Shwachman-Diamond syndrome.
AB  - Shwachman-Diamond syndrome (SDS), described just under 40 years ago, is a rare,
      autosomal-recessive disorder usually manifest in infancy and characterized by
      exocrine pancreatic insufficiency, short stature, and bone marrow dysfunction.
      Additional clinical features include metaphyseal dysostosis, epiphyseal
      dysplasia, immune dysfunction, liver disease, growth failure, renal tubular
      defects, insulin-dependent diabetes mellitus, and psychomotor retardation.
      Hematological manifestations other than neutropenia include anemia, raised fetal
      hemoglobin (HbF) levels, thrombocytopenia, impaired neutrophil chemotaxis, and
      aplastic anemia; as with other constitutional bone marrow failure syndromes,
      there is a predilection to malignant myeloid transformation. No unifying
      pathogenetic mechanism(s) has yet been shown to be responsible for SDS, although
      new insights into the molecular, genetic, and cellular basis of this rare disease
      have recently been described.

PMID- 11957192
TI  - Glycogen storage disease.
AB  - Glycogen storage disease (GSD) is a rare autosomal-recessive disorder
      characterized by hypoglycemia, hepatosplenomegaly, seizures, and failure to
      thrive in infants. Neutropenia and/or neutrophil dysfunction develops in GSD1b,
      but not in other types. GSD1b results from a deficiency of the glucose-6
      phosphate translocase enzyme and the genetic defect maps to chromosome 11q23.
      Patients with GSD1b are susceptible to recurrent bacterial infections, commonly
      involving the perirectal area, ears, skin, and urinary tract, although life
      threatening infections, such as septicemia, pneumonia, and meningitis occur less
      frequently. Although the exact mechanism of neutropenia in patients with GSD1b is
      not known, treatment with recombinant human granulocyte colony-stimulating factor
      (G-CSF) has reduced the incidence of infections and has improved the quality of
      life of these patients. Defects in neutrophil chemotaxis and intracellular
      bacterial killing have been described and appear to be corrected by the use of G
      CSF. To date, no cases of myelodysplasia or acute myeloid leukemia have been
      observed in patients with GSD1b treated with G-CSF. A significant complication of
      cytokine therapy is the development of hypersplenism, requiring either a
      reduction in the dosage of G-CSF or splenectomy.

PMID- 11957193
TI  - Neutropenia associated with primary immunodeficiency syndromes.
AB  - The primary immunodeficiency diseases are a heterogeneous group of more than 75
      disorders characterized by intrinsic defects in the functions of the immune
      system. Many are associated with abnormalities of hematopoiesis as well. This
      article will review those primary immunodeficiency syndromes in which neutropenia
      is a prominent finding, including X-linked agammaglobulinemia (XLA), hyper IgM
      syndrome, common variable immunodeficiency (CVID), IgA deficiency, cartilage-hair
      hypoplasia (CHH), and reticular dysgenesis, with regards to pathophysiologic
      findings and treatment.

PMID- 11957194
TI  - Idiopathic, immune, infectious, and idiosyncratic neutropenias.
AB  - In idiopathic and immune neutropenias the susceptibility to infectious agents is
      highly variable, but the reason why some patients exhibit no undue susceptibility
      whereas others contract life-threatening infections is poorly understood. An
      important factor is the efficacy of delivery of neutrophils to the tissues.
      Recent investigations of the mechanisms for mild to moderate chronic neutropenias
      have shown the significance of interactions between myelopoiesis and the immune
      system, as for example, in relation to immunoglobulin aberrations and the
      cytokine network. Antibody-mediated neutropenias (alloimmune, autoimmune) are now
      well-characterized diseases. If infections occur, apart from antibiotics,
      granulocyte colony-stimulating factor (G-CSF) is the treatment of choice, while
      intravenous or monoclonal immunoglobulins and cyclosporine are reserved for
      refractory cases.

PMID- 11957195
TI  - Chronic neutropenia associated with autoimmune disease.
AB  - Chronic neutropenia with autoimmune diseases is associated mainly with rheumatoid
      arthritis (RA), as Felty's syndrome or large granular lymphocyte (LGL) leukemia,
      and with systemic lupus erythematosus (SLE). Recent advances have allowed better
      understanding regarding the mechanism of neutropenia and improved options for
      treatment. Target antigens for antineutrophil antibodies have been identified for
      both Felty's syndrome and for SLE. The role of soluble Fas-ligand (FasL) in
      inducing apoptosis of neutrophils has been clarified for LGL leukemia and
      increased neutrophil apoptosis has been described in neutropenic patients with
      SLE. The role of immune complexes in affecting neutrophil traffic and function
      continues to be studied. Treatments of neutropenia have included methotrexate,
      cyclosporine A, and granulocyte colony-stimulating factor (G-CSF) as well as
      granulocyte-macrophage colony-stimulating factor (GM-CSF). The efficacy of both
      GM- and G-CSF in reversing neutropenia and decreasing the risk of infections in
      Felty's syndrome and SLE has been well documented. Of concern, however, have been
      flares of symptoms or development of leukocytoclastic vasculitis in some patients
      following the use of these cytokines. Recent results suggest that in these
      patients G-CSF should be administered at the lowest dose effective at elevating
      the neutrophil count above 1,000/microL.

PMID- 11957196
TI  - Risk of myelodysplastic syndrome and acute myeloid leukemia in congenital
      neutropenias.
AB  - Granulocyte colony-stimulating factor (G-CSF) has had a major impact on the
      management of "severe chronic neutropenia" (SCN), a collective term referring to
      congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G
      CSF with increased neutrophils, reduced infections, and improved survival. Some
      responders with congenital neutropenia and Shwachman-Diamond syndrome (SDS) have
      developed myelodysplastic syndrome and acute myeloid leukemia (MDS/AML), which
      raises the question of the role of G-CSF in pathogenesis. The issue is
      complicated because both disorders have a propensity for MDS or AML as part of
      their natural history. To address this, the Severe Chronic Neutropenia
      International Registry (SCNIR) used its large database of chronic neutropenia
      patients treated with G-CSF to determine the incidence of malignant myeloid
      transformation in the two disorders, and its relationship to treatment and to
      other patient characteristics. No statistically significant relationships were
      found between age at onset of MDS or AML and patient gender, G-CSF dose, or
      duration of G-CSF therapy. What was observed, however, was the multistep
      acquisition of aberrant cellular genetic changes in marrow cells from patients
      who transformed, including activating ras oncogene mutations, clonal cytogenetic
      abnormalities, and G-CSF receptor mutations. In murine models, the latter
      produces a hyperproliferative response to G-CSF, confers resistance to apoptosis,
      and enhances cell survival. Since congenital neutropenia and SDS are inherited
      forms of bone marrow failure, G-CSF may accelerate the propensity for MDS/AML in
      the genetically altered stem and progenitor cells, especially in those with G-CSF
      receptor and ras mutations (82% and 50% of patients who transform, respectively).
      Alternatively, and equally plausible, G-CSF may simply be an "innocent bystander"
      that corrects neutropenia, prolongs patient survival, and allows time for the
      malignant predisposition to declare itself. In patients who transform to overt
      MDS or AML, hematopoietic stem cell transplantation is the only chance for cure.
      In those with "soft" signs of MDS, such as an isolated clonal cytogenetic change
      but without other evidence of MDS, or with an isolated G-CSF receptor mutation,
      there is room for conservative management. One option is to reduce the G-CSF
      dosage as much as possible, and observe the tempo of progression, if any, to more
      overt signs of malignancy.

PMID- 11957197
TI  - Risk and benefit of treatment of severe chronic neutropenia with granulocyte
      colony-stimulating factor.
AB  - The Severe Chronic Neutropenia International Registry (SCNIR) was established in
      1994 following four phase I/II and one phase III clinical trial on the use of
      filgrastim (recombinant human granulocyte colony-stimulating factor [r-metHuG
      CSF]) as a treatment for severe chronic neutropenia (SCN). A primary purpose of
      the SCNIR is to monitor SCN patients treated with filgrastim for adverse events
      that might occur over time. As of December 31, 2000, 832 patients with SCN (384
      congenital, 160 cyclic, 288 idiopathic) were enrolled. Clinical trial and
      Registry data show that filgrastim is an effective treatment for SCN; more than
      90% of patients treated respond with normalization of blood neutrophil counts.
      The SCNIR has collected data on bone pain, splenomegaly, hepatomegaly,
      thrombocytopenia, osteopenia/osteoporosis, vasculitis, glomerulonephritis, growth
      and development, pregnancy and fertility, leukemic transformation, and mortality.
      Analysis of data from patients who received filgrastim for up to 11 years did not
      identify any adverse events associated with increased duration of treatment.

PMID- 11957199
TI  - Independent sector. An inspector calls.

PMID- 11957200
TI  - Workplace pressures. A firm hand against stress.

PMID- 11957198
TI  - Ethical issues. Showing a little mercy.

PMID- 11957201
TI  - Bad blood over hepatitis C.

PMID- 11957203
TI  - A right old carry on.

PMID- 11957202
TI  - Is the clinical nurse specialist de-skilling the junior doctor?

PMID- 11957204
TI  - You talkin' to me?

PMID- 11957205
TI  - The returning nurses' rites of passage.

PMID- 11957206
TI  - Should we be taking a walk on the wild side?

PMID- 11957207
TI  - Nursing Times election manifesto.

PMID- 11957208
TI  - The state we're in.

PMID- 11957209
TI  - For the record.

PMID- 11957210
TI  - Who cares if we don't value nurses?

PMID- 11957211
TI  - Deep vein thrombosis--aetiology and prevention.

PMID- 11957212
TI  - Positive inotrope therapy.

PMID- 11957213
TI  - Pain tool audit in coronary care.

PMID- 11957214
TI  - When parents have learning difficulties.

PMID- 11957216
TI  - Fit for practice. Part 4.3: The contribution of nurses.

PMID- 11957215
TI  - Stoma care--4. Fitting a 2-piece appliance.

PMID- 11957217
TI  - Fatal injection inquiry. Nurses added to 'system failure'.

PMID- 11957219
TI  - Nurse with TB triggers mass patient testing.

PMID- 11957218
TI  - 'Don't ignore illegal drugs' warns UKCC.

PMID- 11957220
TI  - Prison health. Call to double nurse numbers.

PMID- 11957221
TI  - Prison suicide checks must be more rigorous.

PMID- 11957222
TI  - Damages for 'gothic horror'.

PMID- 11957225
TI  - Prejudgment. Why it stifles case acceptance and how to overcome it quickly.

PMID- 11957226
TI  - Managing cash flow to improve your bottom line.

PMID- 11957224
TI  - Nitrous oxide analgesia. What is a safe level of exposure for the dental staff?

PMID- 11957227
TI  - PC dependency. The dark side.

PMID- 11957228
TI  - Today's dentists have added responsibilities.

PMID- 11957229
TI  - Intraoral cameras: patient education and motivation.

PMID- 11957231
TI  - Education issues.

PMID- 11957230
TI  - Dental physicians?

PMID- 11957232
TI  - The FDA continues to monitor dental amalgam use.

PMID- 11957233
TI  - Brave new craniofacial surgery.

PMID- 11957234
TI  - What does the doctor want?

PMID- 11957235
TI  - The laminar impression technique.

PMID- 11957236
TI  - Stainless steel reinforced resin retained bridges.

PMID- 11957237
TI  - Predictable pressed ceramic anterior restorations. Clinical observations.

PMID- 11957238
TI  - Risk assessment in periodontal diagnosis and treatment planning. The fundamental
      importance of probing.

PMID- 11957239
TI  - Bonded porcelain restorations. An integral part of aesthetic rehabilitative
      dentistry.

PMID- 11957241
TI  - Grafting the anterior maxilla after tooth loss from external resorption. A case
      report.

PMID- 11957240
TI  - Aesthetic dentistry and prom night.

PMID- 11957242
TI  - Is there a satisfactory alternative to opioids in the management of surgical
      pain?

PMID- 11957243
TI  - Ergonomics in dentistry, Part 1.

PMID- 11957244
TI  - National Health Laboratory Services in Kenya: challenges for the new millennium.

PMID- 11957245
TI  - Laboratory diagnostic services in rural health centres, western Kenya.
AB  - Laboratory diagnosis is an important component of the health care system. It
      serves as a link between the clinician and the patient. Majority of the Kenyan
      community seeks medical care from the rural health centres. The purpose of this
      study was to determine the role of the diagnostic laboratory at the rural health
      centre level. Cross-section data collection method was used. Blood slide for
      malaria parasites was performed in all the health centres. Although clinic
      records indicate that typhoid was among the top ten diseases, Widal test was done
      in only 28.6%, and bacterial cultures in none of the health centres. There is
      need for a variety of essential diagnostic laboratory tests be carried out to
      improve laboratory services at rural health centres.

PMID- 11957246
TI  - Principles of screening for chronic diseases.

PMID- 11957247
TI  - Bone marrow examination at a paediatric hospital in Kenya.
AB  - OBJECTIVE: To investigate the main indications for, and common conditions found
      in bone marrow examinations (BME) of children. METHODS: This was a retrospective
      study from September 1, 1993 to September 3 1998. All bone marrow aspirate and
      trephine biopsy results were retrieved. The clinical data provided by clinicians
      were also noted. RESULTS: A total of 97 BME were recorded from patients aged two
      months to 13 years. The peak ages for BME were six to eight years (24% of
      patients). The more frequent indications for BME were unexplained anaemia found
      in 26% request forms, investigation for solid tumours (10%) and lymphoma (10%)
      and remission assessment after treatment for leukaemia (26%). The main findings
      were malignancy (27%) with leukaemia being commonest (ALL) 16% of patients and
      acute myeloblastic leukaemia (5%). Haematinic deficiency was seen in 12.7% of
      cases with iron deficiency being the commonest. There were some notable
      differences and similarities in the study as compared to a similar one performed
      at a local referral hospital. CONCLUSION: The importance of BME as a crucial
      investigational tool in the management of patients is underscored. Interpretation
      is more meaningful when the haematologist has adequate clinical data.

PMID- 11957248
TI  - McCune Albright syndrome: autosomal dominant trait in a family of eight.

PMID- 11957249
TI  - Clinical presentation and treatment outcome in children with nephroblastoma in
      Kenya.
AB  - OBJECTIVE: To review the clinical presentation and management of children with
      nephroplastoma and the factors influencing the outcome at Kenyatta National
      Referral and Teaching Hospital (KNH). DESIGN: This was a retrospective case
      series study based on secondary data accumulated between 1990 and 1996. SETTING:
      The relevant data were extracted from records of all children aged 12 years and
      below, admitted for cancer at KNH, Nairobi. RESULTS: Out of 803 children with
      cancer, 71 (8.8%) had histologically proven nephroblastoma. At presentation, 1.5%
      were in stage I, 13.2% stage II, 36.8% stage III, 41.2% stage IV and 7.4% stage
      V. Eighty five per cent presented with stage III-V disease. Ninety five per cent
      had nepherectomy and received chemotherapy. Radiotherapy was given to 50.7% of
      the patients. Nine patients died before commencement of chemotherapy, two of whom
      died in the immediate post-operative period. The median duration between
      admission and surgery was 41 days. Pre-operative chemotherapy was given to 42% of
      the patients. Approximately 25.5% of the patients received little or no induction
      chemotherapy due to unavailability of drugs while only 2.8% received the
      prescribed maintenance treatment with the remainder getting erratic or no
      treatment. Overall, only 34.7% remained disease free two years from time of
      diagnosis. CONCLUSION: Late presentation, poor availability of cytotoxic drugs
      and frequent treatment interruptions for various reasons have contributed to the
      poor outcome of nephroblastoma in Kenya.

PMID- 11957250
TI  - Lessons learned from colorectal model of tumourigenesis.
AB  - Genetic analytical techniques were carried out to identify mutations in
      adenomatous polyposis coli (APC) gene and K-ras oncogene in colorectal
      tumourigenesis. These two genes are said to be early mutation genes among other
      mutation genes that constitute the model for colorectal tumourigenesis. To do
      this analysis, DNA was isolated from colorectal formalin fixed paraffin-embedded
      tumour tissue sections. The sections were deparaffinised, digested in proteinase
      K, followed by DNA isolation. The DNA was amplified by Polymerase Chain Reaction
      (PCR), screened by using Denaturing Gradient Gel Electrophoresis (DGGE) or Single
      Strand Conformation Polymorphism (SSCP) and then sequenced. These results lend
      support to the fact that colorectal cancer and indeed cancer in general develops
      through a multi-step process; also that accumulation of genetic mutations
      underlie the development of neoplasia. We are in the process of extending this
      study to cancer of oesophagus to see if a similar or parallel model of
      carcinogenesis holds and in what sequence it is.

PMID- 11957251
TI  - Medico-legal aspects of molecular medicine.

PMID- 11957252
TI  - Fact-finding tour of the oncology services at the Kenyatta National Hospital.

PMID- 11957253
TI  - Adenotonsillectomy.

PMID- 11957254
TI  - Frequency of adenotonsillectomy in some Nairobi hospitals.
AB  - OBJECTIVES: To determine the frequency of adenotonsillectomy in a sample of
      Kenyan hospitals and to review indications, timing and complications in 97 cases
      of adenotonsillectomy done by the authors. DESIGN: Retrospective, descriptive
      study. SETTING: Kenyatta National, Nairobi, Aga Khan, Gertrude and Mater
      Hospitals. RESULTS: Adenotonsillectomy is the most frequent otolaryngologic
      surgical operation. Indications for surgery were upper airway obstruction in
      61.3%, recurrent tonsillitis in 28.7% and both in 7.5%. Surgery was indicated
      during the acute stage in 6.8% of cases. There was one case of post-operative
      acute airway obstruction. Post operative bleeding from the tonsillar bed was
      encountered in 2.1% of cases. CONCLUSION: Adenotonsillectomy is the most common
      otolaryngologic surgical operation in our set-up. The low frequency of
      complications and a short hospital stay puts up a case for routine
      adenotonsillectomy as a day surgery procedure.

PMID- 11957255
TI  - Bacteriology of chronic maxillary sinusitis at Kenyatta National Hospital,
      Nairobi.
AB  - OBJECTIVE: To determine the bacteriology and antibiotic sensitivity of the
      bacterial isolates in chronic maxillary sinusitis patients seen at the Kenyatta
      National Hospital. DESIGN: Cross-sectional study. SETTING: Kenyatta National
      Hospital, ENT department. SUBJECTS AND METHODS: Seventy-three patients had
      bilateral sntral washout done and the lavage submitted for culture and anti
      microbial sensitivity between January and June 1996. RESULTS: Antral lavage
      yielded secretions in 63% of patients but bacteria were cultured in only 28.8% of
      the specimens. The isolates included Streptococcus pneumonia (22.2%),
      Staphylocococus albus (18.5%), Staphylocococus aureus (11.1%) and
      Enterobactericiae (11.1%). Anaerobic bacteria were cultured in 22.2% of the
      specimens. Of the commonly used antibiotics, there was high sensitivity to
      erythromycin, cefadroxyl, chloramphenicol and amoxicillin and poor sensitivity to
      ampicillin, cotrimoxazole and perfloxacin. CONCLUSION: The bacteriology of
      chronic maxillary sinusitis at Kenyatta National Hospital is generally similar to
      that found elsewhere. The bacteria are susceptible to relatively affordable
      antibiotics like amoxicillin, erythromycin and cefadroxyl.

PMID- 11957256
TI  - Management of perforated duodenal ulcer in a resource poor environment.
AB  - BACKGROUND: The majority of literature on the management of perforated duodenal
      ulcer comes from the west. However, this is not necessarily appropriate in the
      developing world where perforated ulcers occur in younger patients, there is a
      strong association with cigarette smoking, and presentation is often delayed.
      OBJECTIVE: An attempt to guide management of perforated duodenal ulcer in the
      developing world using the best evidence available. DATA SOURCES: Review of the
      literature on perforated ulcers and retrospective chart review of cases from a
      rural African hospital. STUDY SELECTION: Relevant studies from the western and
      developing world literature. DATA EXTRACTION: Med-line search. DATA SYNTHESIS:
      Assessment of relevance to clinical management of perforated duodenal ulcers in
      the developing world. CONCLUSIONS: Due to recognition of Helicobacter pylori (HP)
      as a causative agent in duodenal ulcer disease many western surgeons are
      questioning the need for definitive ulcer surgery in the acute management of
      perforated duodenal ulceration. This philosophy may not be appropriate in the
      developing world due to poor HP eradication rates, conditions fostering re
      infection with HP, problems with patient compliance in taking medications, and
      difficulties with follow-up. It is suggested that selected patients, without
      preoperative risk factors, are offered definitive surgery but those at any risk
      of postoperative mortality be treated with conservative surgery and treatment for
      HP. These patients will have to be followed closely to check ulcer healing.
      Attention will also need to be paid to stopping smoking.

PMID- 11957257
TI  - Leukaemia at Queen Elizabeth Central Hospital in Blantyre, Malawi.
AB  - OBJECTIVES: To determine the patterns of leukaemias seen in Malawians at Queen
      Elizabeth Central Hospital (QECH) and to compare the findings with those from
      elsewhere. An overview of the problems encountered in the management of leukaemia
      in developing countries especially those in sub-Saharan Africa are highlighted.
      DESIGN: Retrospective descriptive analysis of consecutive leukaemia cases seen
      from January 1994 through December 1998. RESULTS: Of the 95 leukaemia patients
      diagnosed during the study period, childhood (0-15 years) leukaemia occurred in
      27 (28.4%) patients while adulthood (above 15 years) leukaemia accounted for 68
      (71.6%) patients. The main leukaemia types were: acute lymphoblastic leukaemia
      (ALL) 14 (14.7%), acute myeloblastic leukaemia (AML) 25 (26.3%), chronic myeloid
      (granulocytic) leukaemia (CML) 32 (33.7%), chronic lymphocytic (lymphatic)
      leukaemia (CLL) 22 (23.2%) and hairy cell leukaemia (HCL) two (2.1%) patients.
      Most of the acute leukaemia (AL) cases occurred in the six to 15 year age bracket
      with a male preponderance. In ALL, lymphadenopathy was the commonest presenting
      feature followed by pallor (92.9%) while in the AML group, pallor occurred in 80%
      of cases. Abdominal swelling (87.5%) due to splenomegaly (81.3%) were the main
      clinical features in the CML group whereas lymphadenopathy (63.6%) followed by
      splenomegaly (59.1%) were the dominant presenting features in CLL.
      Haematologically, although leucocytosis characterised both acute and chronic
      leukaemias, most cases of acute leukaemia presented with more severe anaemia (Hb
      < 7 g/dl) and marked thrombocytopenia (Platelet count < 50 x 10(9)/l) than the
      chronic leukaemias. CONCLUSIONS AND RECOMMENDATIONS: The study shows that
      leukaemias are not rare in Malawi and cases which were diagnosed in this series
      probably only represent the tip of the iceberg. While there is need to increase
      diagnostic awareness among clinicians and laboratory staff, the severe chronic
      shortage of cytotoxic drugs and lack of supportive care facilities commonly
      encountered in developing countries should be realistically addressed through
      cost-sharing, cost recovery, adequate government subvention and donations from
      charitable organisations.

PMID- 11957258
TI  - Acute appendicitis in a Kenyan rural hospital.
AB  - OBJECTIVES: The literature on appendicitis in Africa is almost all derived from
      urban teaching hospitals. As most of Africa's people are from rural areas, we
      sought to review our experience from a rural hospital in Kenya. DESIGN:
      Retrospective chart review. SETTING: A rural Kenyan church hospital. SUBJECTS:
      One hundred and twelve cases of acute appendicitis presenting at Kijabe Hospital
      over a five year period were reviewed. INTERVENTION: Appendicectomy. MAIN OUTCOME
      MEASURES: Sex, age, pre-hospital delay, operative findings, wound infection, post
      operative length of stay. RESULTS: The male to female ratio was 1.8:1. The median
      age was 29 (4-71 years). Median prehospital delays were one day (normal
      appendix), one and a half days (simple appendicitis), three days (perforated
      appendix) and six and a half days (appendical abscess). Operative findings were
      14% normal appendix, 42% simple appendicitis, 22% perforated, 21% abscess.
      Overall wound infection rate was 22%; ranging from 11% for simple appendicitis to
      46% for an appendiceal abscess. The mean post-operative length of stay was nine
      and a half days. CONCLUSIONS: Acute appendicitis in rural Kenya is similar to
      patterns reported in urban African centres. The main difference from western data
      is the high complicated appendicitis rate which is most likely related to
      prolonged pre-hospital delay.

PMID- 11957259
TI  - Benign breast diseases in an Afro-Caribbean population.
AB  - BACKGROUND: The diagnosis and effective treatment of benign breast disease still
      remains a clinical challenge and the need for surgical intervention has not been
      clearly defined. OBJECTIVES: To determine the patterns of benign breast disease
      in an Afro-Caribbean population in order to define the patterns of disease
      encountered and to review the approach to diagnosis and treatment. METHODS: A
      review of all breast biopsy operations performed for benign disease at the
      Kingston Public Hospital, Jamaica was made by examining a total of 333 patient
      records over a two year period. RESULTS: Of the cases reviewed this study clearly
      showed that the majority of benign breast lesions were due to fibrocystic disease
      (41%) and fibroadenomas (33%). Intraduct papillomatosis which accounted for 6.7%
      was the next in frequency. Other diseases found included fat necrosis 12 (4.4%)
      with breast abscess and mammary duct ectasia in eight patients (3%) each.
      Fourteen patients (5%) had no diagnostic abnormality. The mean age of patients
      with fibroadenoma was 20 years whereas the mean age of patients with fibrocystic
      disease was 40 years. The co-existence of fibrocystic disease with malignancy was
      reported in 15 cases. CONCLUSION: Benign breast disease in this population occurs
      mainly in young women less than 30 years of age. Eighty per cent of breast
      biopsies done in patients with palpable lumps are for benign disease. The data
      support a more conservative approach to diagnosis and management of these
      patients.

PMID- 11957260
TI  - Expression of oestrogen and progesterone receptors, Ki-67, p53 and BCL-2
      proteins, cathepsin D, urokinase plasminogen activator and urokinase plasminogen
      activator-receptors in carcinomas of the female breast in an African population.
AB  - OBJECTIVE: To determine the expression of oestrogen (ER) and progesterone
      receptor (PgR), Ki-67, p53, bcl-2 proteins and the proteolytic enzymes cathepsin
      D (CD), urokinase-plasminogen activator (uPA) and its receptor (uPA-R) in primary
      carcinomas of the breast from indigenous Tanzanian female patients by
      immunohistochemistry. DESIGN: Prospective cross-sectional study. SETTING:
      Muhimbili Medical Centre, Dar es Salaam, Tanzania. SUBJECTS: Sixty patients
      admitted between 1995 and 1997. RESULTS: Markers were found to be expressed as
      follows: ER (33.3%), PgR (18.3%), p53 (30%), bcl-2 (43.5%) and the median
      proliferation rate of Ki-67 was 15%. Proportion of tumours positive for ER, PgR
      and bcl-2 initially decreased to 12 months disease duration, after which it
      increased. The observed proliferation rate approaches that reported in developed
      countries. p53 expression did not influence the proliferation rate nor did bcl-2
      expression. ER, PgR and bcl-2 were strongly co-expressed. CD was predominantly
      expressed in stromal macrophages than in cancer cells. CONCLUSION: The low
      expression of ER and PgR and their strong co-expression with bcl-2 might
      negatively influence response to hormonal therapy. The influence of bcl-2 on
      tumour response to anti-cancer therapy in patients with long disease duration
      requires urgent clarification. Determination of CD in stromal macrophages rather
      than in cancer cells may have greater prognostic significance in patients of this
      region.

PMID- 11957261
TI  - Splenic size determination in sickle cell anaemia: an ultrasonographic study.
AB  - OBJECTIVES: To examine the generally accepted concept of autosplenectomy in
      patients with sickle cell anaemia, and determine the relationship between age,
      the steady state PCV and splenic size. DESIGN: Case-control study. SETTING:
      Sickle Cell Clinic, University of Ilorin Teaching Hospital, Ilorin, Nigeria.
      SUBJECTS: Sickle cell anaemia patients aged three to 47 years, while the controls
      included age and sex matched patients attending the General Outpatient Department
      for minor ailments. INTERVENTIONS: Longitudinal and coronal sizes of the spleen
      were measured antemortem, by ultrasonographic method, in 98 adult sickle cell
      anaemia patients and 48 control subjects and compared. The splenic size was
      correlated with age and PCV among sickle cell anaemia patients. MAIN OUTCOME
      MEASURES: Determination of longitudinal and coronal sizes of the spleen,
      comparison of mean splenic sizes of patients with those of controls by Student's
      t test, and correlation of age and PCV with splenic sizes. RESULTS: Both mean
      longitudinal and coronal diameters, and surface area were found to be higher in
      the sickle cell anaemia patients compared to the controls. While the longitudinal
      diameter increased with age continuously, the coronal diameter decreased after
      the age of 30 years. There were no significant correlations between the splenic
      sizes and PCV and number of crises per year. CONCLUSION: The general belief that
      sickle cell anaemia patients suffer anatomical autosplenectomy was not confirmed.
      This could be due to the effect of malaria and improved clinical care.

PMID- 11957263
TI  - Survival advantage in female patients with sickle cell anaemia.
AB  - OBJECTIVE: To evaluate the clinical and laboratory features of adult sickle cell
      anaemia patients in Nigeria. DESIGN: A cross-sectional study. SETTING:
      Haematology clinic of the University College Hospital, Ibadan, Nigeria. SUBJECTS:
      Sixty nine adult sickle cell anaemia patients randomly sampled. RESULTS: The mean
      steady state haematocrit, HbA2 and HbF were 22%, 4.6% and 7% respectively. Twenty
      five per cent of the patients had never received blood transfusion and a similar
      proportion recorded an infrequent occurrence of painful crises. CONCLUSION: An
      improved survival was observed with female patients showing an age related
      survival advantage over the males. Persistent splenomegaly was observed less
      frequently in the Nigerian sickle cell population despite the high frequency of
      alpha thalassaemia in the region. This was thought to be due to the lower levels
      of HbF in this population.

PMID- 11957262
TI  - Nadir neutrophil counts in patients treated for breast cancer with doxorubicin
      and cyclophosphamide.
AB  - OBJECTIVE: To determine the impact on neutrophils if adriamycin is administered
      at 60 mg/m2 and cyclophosphamide at 600/m2 (AC 60/600); and at 50 mg/m2 and 500
      mg/m2 (50/500) in the treatment of breast cancer. DESIGN: Restrospective analysis
      of nadir neutrophil counts in female mammary carcinoma patients treated with
      adriamycin/cyclophosphamide combination. SETTING: Hurlingham Oncology Clinic,
      Nairobi and The Nairobi Hospital between March 1995 and August 1999. SUBJECTS:
      Eighteen patients with breast cancer were treated either for adjuvant purposes or
      for metastatic disease. INTERVENTION: Chemotherapy with adriamycin and
      cyclophosphamide at 60/600 or 50/500. Patients were advised to avoid crowded
      places and given prophylactic broadspectrum antibiotics whenever grade 4
      neutropenia occurred at nadir. RESULTS: Grade 3-4 neutropenia occurred in 75.5%
      of treatments at 60/600 and in 56.8% of the treatments at 50/500. Febrile
      neutropenia followed only one treatment and did not result in death. CONCLUSION:
      Neutropenia is frequent and severe at A/C 60/600 and need to be watched out for.
      Sepsis on the other hand is prevented if meticulous attention is given and
      corrective measures taken. A/C 50/500 was associated with less occurrences of
      neutropenia though still very high. Neutropenia should therefore be checked and
      steps be taken to prevent sepsis even at this dosage.

PMID- 11957264
TI  - Experience with vincristine--associated neurotoxicity.
AB  - OBJECTIVES: To evaluate the frequency and severity of occurrence of vincristine
      associated neurotoxicity. DESIGN: A retrospective case series study. SETTING:
      Hurlingham Oncology Clinic, Nairobi. SUBJECTS: Thirty-eight patients treated for
      various neoplasms with vincristine containing chemotherapeutic regimens. MAIN
      OUTCOME MEASURES: The frequency and degree of neurotoxicity when vincristine was
      given at the standard dose of 1.4 mg/m2. RESULTS: Five patients (13.2%) developed
      peripheral neuropathy, one having had it even before vincristine was started.
      Therefore only four (10.5%) had it attributed to vincristine. Four of the
      patients who developed neuropathy (80%) were HIV-positive. Neuropathy grade 2
      (severe) occurred in only two patients leading to discontinuation of the drug.
      All the neurotoxicity resolved after discontinuation of vincristine. CONCLUSION:
      Vincristine induced neuropathy occurred but was rarely severe at a dose of 1.4
      mg/m2. It appeared to be more frequent in HIV infected individuals, but
      controlled studies with bigger sample sizes are required to determine whether
      this may warrant routine capping of the dose at a maximum of 2 mg.

PMID- 11957265
TI  - Surgical output in Kibaale district, Uganda.
AB  - BACKGROUND: The output of major surgeries in eastern Africa is low and varies
      considerably between hospitals and regions. This study in rural Uganda relates
      surgical output to number of hospital beds, number of in-patient admissions,
      number of new out-patient visits, estimated catchment area population and number
      of doctors and nurses. This was to facilitate comparison between institutions and
      areas and to determine surgical resource needs. OBJECTIVES: To describe the
      quantitative output of surgery in a Ugandan district and to demonstrate the use
      of standardised indicators for the purpose of comparison, monitoring, resource
      needs assessment and planning. DATA SOURCES: Retrospective review and analysis of
      inpatient and outpatient records at Kagadi district hospital, Kibaale district,
      Western Uganda, the only hospital providing major surgery in the district. STUDY
      SELECTION: Data on all recorded major and minor surgical operations in the
      hospital during two complete calendar years, 1996 and 1997. DATA SYNTHESIS: In
      1996 and 1997 there were 331 and 309 major operations performed respectively in
      Kagadi hospital, Kibaale district. This output corresponded to 3.3 and 3.1 per
      100 beds; 270 and 270 per 1,000 in-patient admissions; 328 and 267 per year per
      10,000 new out-patient visits; 166 and 155 per 100,000 catchment area population;
      83 and 77 per doctor; 27.6 and 25.8 per nurse. Minor surgery output at the same
      hospital in 1996 and 1997 were 185 and 190 respectively. This corresponded to 183
      and 164 per 10,000 new outpatient visits and 93 and 95 operations per 100,000
      catchment area population. CONCLUSIONS: The output of surgery in the district was
      very low in comparison with Europe and North America but within the range common
      in Eastern Africa. For planning and performance review purposes the most useful
      indicators are surgical output per 100 beds per year; per 1000 inpatient
      admissions; per doctor and per nurse per year because they measure workload
      against available resources. Output per 100,000 estimated catchment area
      population is useful in relating output to need. These indicators are recommended
      to be incorporated in district and hospital performance reviews and in annual
      reports.

PMID- 11957266
TI  - Attitude and social consequences of tuberculosis in Addis Ababa, Ethiopia.
AB  - OBJECTIVE: To gain a better understanding of the attitude and social consequences
      of tuberculosis (TB) in Addis Ababa, Ethiopia. DESIGN: A cross sectional survey
      using a structured questionnaire and a qualitative study based on the focus group
      discussion (FGD) technique. SETTING: Eight different kebeles (urban dwellers'
      associations) of six woredas (next higher administrative level to kebele).
      SUBJECTS AND METHODS: Seven hundred and three participants, comprising 326 males
      and 377 females were interviewed using the written questionnaire and 36 recent
      and current TB patients through focus group discussion. Data were analysed using
      SPSS/PC statistical package. The proportions were compared using univariate and
      bivariate analyses to show the frequency distribution and evaluate the
      relationship among different variables. In FGD, topics relevant to the research
      questions were identified, sorted and analysed. Conclusions were then formulated.
      MAIN OUTCOME MEASURES: Attitude of participants towards TB and its victims and
      social consequences of being a TB patient. RESULTS: Eighty three per cent of the
      respondents were aware that TB is a disease transmitted from one person to
      another and 80.1% perceived TB as an extremely severe disease. Of the total,
      81.5% answered that TB is caused by cold, 69.0% feel that TB patients are not
      accepted in the community and 78.3% fear physical contact with TB patients. Most
      participants of the FGD sessions agreed that TB is a very dangerous, contagious
      but curable disease and the community has a generally negative attitude towards
      them. They also think that TB is associated with HIV/AIDS in the society. These
      attitudes have social consequences particularly the stigmatization and social
      isolation of TB patients. Four hundred and four (57.5%) respondents were found to
      be in favour of the short course chemotherapy against 226 (32.1%) choosing the
      longer course. Clinical improvement and unavailability of some drugs or their
      cost were the first and second main reasons indicated, respectively, for
      defaulting by respondents. CONCLUSION: The perception by most respondents that
      tuberculosis is incurable, transmittable and associated with HIV/AIDS, led to the
      understanding that TB is a very dangerous disease. This, in turn, contributes to
      social avoidance and the resultant consequences in TB patients. Health education
      must be stepped-up within the TB control programme, and the psychosocial
      implications of TB should be given due attention.

PMID- 11957267
TI  - Primary chest Hodgkin's disease diagnosed by pleural biopsy: case report.
AB  - Hodgkin's disease involving the lung and pleura is rare. A case of a 40-year-old
      woman with one year history of pain in the left arms spreading into chest is
      presented. Computed tomography showed a mass of 5 x 7 cm in the left hemithorax
      mediastinum and pleura, pleural effusion and mediastinal lymphadenopathy.
      Diagnostic methods including percutaneous needle aspiration biopsy of pleura,
      brochoscopic biopsies, bronchoalveolar lavage, cytological examination of the
      pleural fluid did not disclose any pathological diagnosis. Lastly, we performed
      pleural biopsy by video-assisted thoracoscopic surgery and we showed that the
      lesion was HD of nodular sclerosing type.

PMID- 11957268
TI  - Low risk and high risk human papillomaviruses (HPVs) and cervical cancer in
      Zimbabwe: epidemiological evidence.
AB  - OBJECTIVE: To establish the prevalence of detectable low-risk and high-risk,
      oncogenic HPV types in cervical swabs of women with histologically proven cancer
      of the cervix. DESIGN: Cross sectional study. SETTING: Harare Central and
      Parirenyatwa Hospitals. SUBJECTS: 119 women with histologically proven cervical
      cancer of whom 63 had the degree of differentiation of the tumour reported. MAIN
      OUTCOME MEASURES: Frequency of infection with high and low-risk human
      papillomaviruses. RESULTS: The presence of HPV DNA was demonstrated in 63%
      (75/119) of cases. Low risk HPVs were present in 26% (31/119) and high-risk HPVs
      were demonstrated in 51% (61/119) of samples tested. Co-infection with both low
      risk and high-risk HPVs was observed in 14% (17/119) of the specimens. High-risk
      HPVs were detected in 55% (21/38) of poorly differentiated tumours while 60%
      (15/25) of moderately and well-differentiated tumours showed the presence of high
      risk HPVs. CONCLUSION: High-risk human papillomaviruses are associated with
      cervical cancer. There was no significant difference in the frequency of high
      risk HPV types in women with moderately to well-differentiated tumours and those
      with poorly-differentiated tumours.

PMID- 11957270
TI  - Two years maternal mortality in Matebeleland north Province, Zimbabwe.
AB  - OBJECTIVE: To describe timeliness and completeness of maternal mortality
      notifications after the introduction of a revised national notification form in
      1998, as well as socio-demographic and obstetric variables and causes of maternal
      deaths. DESIGN: Retrospective descriptive study. SETTING: Seven districts in
      Matebeleland North province. SUBJECTS: 95 maternal death notifications from 1
      August 1998 to 31 July 2000. MAIN OUTCOME MEASURES: Delay in submission and
      completeness of reports, age, marital status, religion, reproductive history,
      booking and referral status, duration and outcome of pregnancy, place of death,
      cause of death. RESULTS: 92/95 notifications were true maternal deaths, 86% were
      notified within 48 hours and 79% were complete, 74% of the deaths took place in a
      health facility. Mean age of the women was 27.8 years, mean parity 3.0. Sixty
      percent had booked. The five main causes of death were obstetric haemorrhage
      (26%), malaria (24%), immune deficiency syndrome (13%), abortion (11%) and
      eclampsia (8%). The maternal mortality ratio per 100,000 reported home and
      institutional live births ranged from 155 to 532 per district. CONCLUSION: There
      is under reporting of maternal mortality in some districts, although from 1997 to
      2000 a 200% increase in reporting was seen. Timeliness and completeness of
      reporting was satisfactory. With the exception of a high contribution from
      malaria the causes of maternal mortality in Matebeleland North province are
      similar to those reported elsewhere in Zimbabwe.

PMID- 11957269
TI  - Injection-induced sciatic nerve injury in Nigerian children.
AB  - OBJECTIVES: A retrospective study of all children with a diagnosis of sciatic
      nerve injury managed at the University College Hospital, Ibadan, Nigeria over a
      12 year period was carried out in order to determine predisposing factors to the
      nerve injury and highlighting practical preventive measures. DESIGN: The
      necessary data was collected from the case files of children seen at the hospital
      with a diagnosis of sciatic nerve injury, from 1988 to 1999. RESULTS: There were
      27 children aged five months to 12 years with a diagnosis of sciatic nerve
      injury. Twenty (74%) of the children were aged five years or less. While seven
      patients (26%) presented within two weeks of development of foot drop consequent
      on intramuscular (i.m.) injection given on the buttock, 20 patients (74%)
      presented much later. Fever was the most common complaint for which the injection
      had been given. The identity of the drugs given was not known in 10 patients. In
      the remaining 17 patients drugs administered were specified and included
      Chloroquine, Novalgin, Paraldehyde, Procaine penicillin, and Sulfadoxine
      Pyrimethamine. Most of the patients had received the injections in privately
      owned medical facilities where staff with minimal training are often allowed to
      administer i.m. injections. CONCLUSION: It is suggested that the i.m. route for
      injection be strongly discouraged when a drug can be given by other routes. Only
      trained staff should be allowed to administer i.m. injections. Giving i.m.
      injections at sites other than the buttock maybe advantageous in children
      particularly those aged five years and below.

PMID- 11957271
TI  - Heterotopic pregnancy of a ruptured ectopic pregnancy coexisting with a twin
      intra-uterine pregnancy: a case report.
AB  - A case of ruptured ectopic and twin intra-uterine pregnancy is presented. The
      patient had conceived following ovulation induction with clomiphene citrate.

PMID- 11957272
TI  - Sinister unilateral tonsillar enlargement.

PMID- 11957273
TI  - Symptomatic spinal cord involvement in prostate cancer.
AB  - The literature on spinal cord involvement in prostate cancer is reviewed by
      searching the Medline from 1965 to 1997 and references in publications on the
      subject. The objective was to identify the clinical characteristics and treatment
      modalities of the disease. Prostate cancer is the leading cause of metastatic
      spinal cord disease in men. The tumour reaches the spinal column mainly by the
      venous route. The frequency of involvement in decreasing order is thoracic spine,
      lumbar spine and cervical spine. The tumour usually exerts compression of the
      cord from the extradural space. However, intradural and intramedullary metastases
      have devastating effects. The patients have other neurological and urological
      symptoms prior to the onset of paraplegia. But in some, spinal cord compression
      may be the first symptom of prostate cancer. Plain X-rays may suffice in
      diagnosis but MRI is the single most valuable investigation for anatomic
      definition or localization of spinal cord secondaries. All forms of treatment are
      palliative. Treatment options, singly or in combination, include hormonal
      manipulation, radiotherapy and laminectomy each often with high dose
      corticosteroids. Recurrence of symptoms after an initial relief with hormonal
      manipulation signifies escape of the tumour from endocrine control and portends a
      poor prognosis.

PMID- 11957274
TI  - [Anatomical study of the interosseous membrane of the forearm].
AB  - The authors have dissected 20 forearms of human cadavers to study anatomy and
      some functions of the IOM. The fibers bundles of the IOM were arranged in one
      plane descending obliquely and distally from the radius to insertion to the ulna.
      Central band of the IOM was easily found and was thick. It's a resistant ligament
      for longitudinal stability of the radius. Now, it's important to know anatomical
      alignment of the IOM because ultrasound imaging can be used for diagnosis of its
      rupture or elbow injuries and in a early future, surgical methods of repair or
      reconstruction of IOM will be developed.

PMID- 11957275
TI  - [Aflatoxins in food: tests of decontamination of peanut cakes by ionizing
      treatment].
AB  - The efficacy of ionising treatment for decontaminating peanut cakes was tested.
      The influence of cakes water content and the effect of ionisation dose rate were
      studied. The results obtained after a reverse phase liquid chromatographic
      determination of B1, B2, G1 and G2 aflatoxins have revealed an important
      contamination of the peanut cakes (up to 1000 ppb of total aflatoxin's contents).
      After ionising treatment at 25 kGy, the aflatoxins degradation in peanut cake's
      was less important in dried samples (about 5-10% at 0.55 water activity: aw) than
      in the humid ones (40-60% degradation at 0.95 water activity). At this dose, any
      indicative difference of the degradation rate of aflatoxins, with regard to the
      ionising process was observed. The efficacy of ionising treatment for
      decontaminating peanut cakes could probably be improved, however the economic
      interest of such process as alternative of the treatment with ammonia is
      questionable.

PMID- 11957276
TI  - [Pesticide bioaccumulation: measurement and levels of organochlorine residues in
      products of vegetable origin].
AB  - Because of their lipophilic properties and their persistence, organochlorine
      pesticides residues can be accumulated in human body by consuming regularly
      plants products. This study consisted of the monitoring of the contamination
      level of pesticides residues from various plants products, in order to assess the
      long- term intoxication risk to which Senegalese consumer is exposed ant identify
      throughout these plants some indicators of atmospheric pollution. The
      chromatographic analysis of medicinal plants, fruits and vegetables extracts
      showed that they could be contaminated by organochlorine residues. About ten of
      these pesticides residues were found confirming that the analysed plants were
      really contaminated. The residues level in medicinal plants (from 0.1 to 45
      micrograms/kg) were widely below the maximum allowed concentrations and were also
      lower than those in fruits and vegetables (from 0.1 microgram/kg to 460
      micrograms/kg). Heptachlorine residues contents of tomatoes and citrus fruits
      were higher than FAO/WHO norms, so that, a regular monitoring of the plants
      products is recommended for better protection of consumers.

PMID- 11957277
TI  - [Prevalence of diabetic retinopathy at the Dakar University Hospital Center].
AB  - The aim of the study is to appreciate the prevalence of diabetic retinopathy
      among senegalese patients in analyzing age of diagnosis, duration of diabetes,
      plasma glucose and type of retinopathy. 129 diabetics followed and treated in the
      diabetic center of internal medicine clinic (Dakar University) were examined by
      90 degrees Volk's lens. A determination of plasma c peptide and glucose
      concentration were performed. 55 (mean age 224. +/- 0.9 years) were insulino
      dependent and 74 (mean age of 54.7 +/- 11.4 years) non insulinodependent. On
      average the duration of diabetes was 5.4 years +/- 5.4 for the former and 6.07 +/
      5.7 for the latter with respectively glucose plasma average 2.60 g/l +/- 0.7 and
      1.7 g/l +/- 0.83. Retinopathy was found in 29 patients. So total prevalence was
      22.48%, shared in 29.7% for non insulino-dependant and 12.7% for insulino
      dependent. In 7 cases the retinopathy was proliferative and non proliferative in
      22 cases essentially among non insulino-dependant diabetics. The diabetic
      retinopathy is one of handicaping complications of diabetics. Its prevalence is
      strongly linked to the duration of diabetes, glycaemic control and to other risk
      factors (genetics, glycosylated hemoglobin and high blood pressure).

PMID- 11957278
TI  - [Neuropediatrics: epidemiological features and etiologies at the Dakar neurology
      service].
AB  - Child neurology is a relatively young speciality of neurosciences which is at the
      frontier of Neurology and Paediatrics. Its development has been impulsed by the
      diagnosis techniques such as Neurobiology, Genetics, Neuroimaging and pedo
      psychology. We conducted a retrospective survey among the in-patients from
      January 1980 to December 1997 in the service of Neurology of the University
      Hospital. Have been included children ranged from 0 to 15 years old without any
      racial, sexual or origin distinctive. In Neurology Department, children of 0 to
      15 years old represent 10.06% of the in-patients received from 1980 to 1997. The
      mortality rate was 9.23%. The diseases are dominated by epilepsy and infantile
      encephalopathies with 31.02%, infectious diseases with 19.36% represented by
      tuberculosis, other bacterial, viral and parasitical etiologies, tumors with
      10.36%, vascular pathology and degenerative disorders.

PMID- 11957279
TI  - [Association between Class I HLA alleles and HBs antigen carrier status among
      blood donors in Senegal].
AB  - The course of hepatitis B virus (HBV) infection may be influenced by the host
      immune response. A prospective study was carried out in ninety-eight subjects
      (mean age = 23 years) HBs antigens carriers of hepatitis B and living in Dakar,
      Senegal. We analysed the HLA-A, -B, and C antigens distribution compared to that
      one of a control (HBs negative) healthy senegalese population (n = 96) living in
      Dielmo village where a longitudinal study was set-up since 1990. The HLA class I
      typing was performed by microlymphocytotoxicity assays. The most frequent HLA-A, 
      B, -C antigens found were: locus A: A23 (33.6%), A2 (25%), A30 (25%), locus B: B8
      (31%), B7 (16.3%), B58 (11.9%), B35 (11%), B49 (11%), B53 (10.8%) and locus C:
      Cw7 (39.1%), Cw17 (39.1%), Cw3 (36.9%), Cw4 (36.6%). Significant differences (P <
      0.001) were found between the donors and the control group for the following HLA
      antigens: A1, A23, B8 and Cw3. The detection of HBe antigen was positive in 26/84
      blood donors. It was observed a significant difference (p < 0.01) between
      positive and negative HBe donors for HLA-A1 allele with an odds ratio of 6.25.
      All the donors carrying the HLA haplotype: A1-B8-Cw7 (11.5%) were positive in HBe
      antigen. HLA: B8-Cw7 haplotype (detected in 8.5% of positive donors) seems to be
      likely associated with a liver cancer according to many reports. An adequate
      follow-up should be set-up for positive HBe subjects carrying a susceptible HLA
      type.

PMID- 11957280
TI  - [Complement and serum immunoglobulins in homozygous and heterozygous sickle cell
      anemia in Senegal].
AB  - Sickle cell disease is an hereditary hemoglobinopathy syndrome which provokes
      deglobulization crisis and infectious complications. These infectious diseases
      may be due to a permanent activation of the immune system. The aim of our study
      was to explore alternative pathway by measuring C3 complement and the classical
      pathway by C4 complement. The level of immunoglobulins IgA, IgG and IgM was also
      measured in the subjects sera. Thirty homozygous sickle cell anemia (SS), 25
      heterozygous (AS) and 34 controls subjects (AA) were recruited in the Hopital
      d'Enfants Albert Royer (HEAR), Fann hospital and Centre National de Transfusion
      Sanguine (CNTS). Radial Immunodiffusion (RID) technics using specific antisera
      for C3c, C4c, IgA, IgG and IgM were used in our study. Homozygous SS proved an
      increase level of IgA (50%, p < 0.003) and IgG (47%, p < 0.003), unlike of IgM
      level. The C3c complement decrease significantly in (27%) of homozygous SS
      patients (p < 0.0005) unlike of C4c level. This low level of C3 and IgG in sickle
      cell homozygous patients can explain the higher susceptibility to infection in
      these patients. Normal level of C4 and low level of C3 show activation of
      alternative pathway. Heterozygous AS showed a normal level of C4, C3 and
      immunoglobulins. Our results suggests a direct involvement of the complement
      system in sickle cell disease and the depletion of C3 registered was a possible
      cause of increased susceptibility to infections in patients with homozygous
      sickle cell anemia.

PMID- 11957281
TI  - [Nosocomial urinary stent infection at the urology service of the Cocody
      University Hospital Center].
AB  - One of the most common complication of urinary stent is urinary infection. At the
      Cocody University, 28 men and 2 females who had a urinary stent were evaluated
      for urinary infection, bacterial growth, and their sensitivity to antibiotics. In
      85.71% of the cases, the bacteriologic analysis was positive for a mean duration
      of urinary drainage of 32, 62 days (range 03 to 90 days). Bacterial isolates
      were: 11 cases of Klebsiella spp, 5 cases of Providencia spp; 1 case of
      Escherichia coli, 1 case of Serratia marcescens. Among these bacteria, 77.78%
      were resistant to most of the antibiotics. Therefore, stent urinary infection is
      mostly due to multi resistant bacteria. Treatment needs an adapted antibiotherapy
      after removal of the causative agent.

PMID- 11957282
TI  - [Traumatic jejuno-ileal ruptures: apropos of 18 cases at the Central Hospital of
      Yaounde].
AB  - Eighteen blunt small bowel traumas were reviewed in this retrospective study
      (1986-1996) concerning 12.8% of laparotomies for blunt abdominal trauma. The
      clinical presentation at admission was peritonitis (9 cases) or hemoperitoneum (4
      cases) whereas 5 cases were diagnosed lately because of non specific signs at the
      beginning. All patients underwent surgery: simple suture or suture after excision
      of edges (12 cases); resection anastomosis (6 cases). There were no post
      operative complications in most of the cases. The mortality rate was 5%. Blunt
      small bowel traumas are not frequent in our practice. Their diagnostic is often
      per-operative. If the clinical signs of intraperitoneal lesion are not present, a
      clinical follow-up by repeated and thorough physical examination can permit an
      early diagnosis. The surgical treatment is simple, and the prognosis more linked
      to severe associated lesions than the bowel lesion.

PMID- 11957283
TI  - [Transverse study comparing certain physical characteristics of Senegalese
      children and adolescents from 7 to 13 years of age].
AB  - 350 boys and 350 girls 7 to 13 years of age that are equally divided into 7 age
      groups according to sex, have been submitted to action speed tests (pure speed),
      co-ordination-speed, pure-power, co-ordination-power, flexibility and balance.
      The objective of our study was to compare the average evolution of each of these
      qualities according sex and age. From 7 to 13 boys were more performing than the
      girls in the first four tests; it's the opposite when il comes to the last two
      ones. Yet, the differences shown on both sides were not altogether significant
      but in action--speed (except at 9) and in flexibility. The two sexes were
      significantly different at the age of 7 and from 9 to 10 in balance, from 10 to
      13 in pure-power, from 11 to 13 in co-ordination-power and from 12 to 13 in co
      ordination-speed. It is often from the age of 7 to 9 or 10 that the average
      yearly gains of the performances are significant. Among the girls, they undergo
      more noticeable reductions from 9 or 10 until 12, before to decrease between 12
      and 13 (in pure speed, co-ordination-speed and pure power), whereas the boys',
      for all the above mentioned physical qualities, remain unchanged or increase in a
      more significant way (except in flexibility). These significant results suggest a
      diversification of motor learning contents for boys and girls of the same age, or
      of different age according to sex.

PMID- 11957284
TI  - [Death from ammonia poisoning: anatomo-pathologic features].
AB  - The authors report the results of a chronological study of anatomo-pathological
      aspects observed in the autopsy of subjects who died after a heavy ammonia
      poisoning. It is about a retrospective study based on the medico-legal autopsies
      of 91 cases of death an industrial ammonia tank explosion which occurred inside a
      factory in Dakar (SONACOS), on the 24th of March 1992. The census of the dead has
      been made during the three months following the explosion. The victims were
      between 3 months and 74 years old. Among the 91 dead there were 15 women and 76
      of the male sex. The recent lesions were discovered in the subjects who died
      during the first three days. The consisted of some extended cutaneomucous burns,
      a sharp lung oedema sometimes associated with a pulmonary emphysema. Later on,
      results show that deaths are rather caused by the after effects of a pneumopathy
      (pulmonary infection, bronchiectasis, pulmonary fibrosis). Ammonia belong to the
      irritating and caustic gas. The intensity of the lesions and the mortal risk are
      proportional to the quantity of gas per m3 of air. If the lesions described in
      our research have similarities with the published description, the latter
      mentions only a few cases of death. The originality of our series is particularly
      found in the intensity of the lesions and the number of deaths. This shows the
      insufficiency of both means of prevention and emergency assistance.

PMID- 11957285
TI  - [Measurement and levels of aflatoxins in small-scale pressed peanut oil prepared
      in the Diourbel and Kaolack regions of Senegal].
AB  - Aflatoxins are mycotoxins produced by some strains of fungus (Aspergillus) which
      develops in peanuts seeds. Peanuts oil and past are very used up in Senegal, then
      the aflatoxins poisoning risk are very actual. This study relates to the
      determination of contamination levels by aflatoxins from peanut oil food prepared
      by small scale production in areas of Kaolack and Diourbel. High Performance
      Liquid Chromatography (HPLC) analysis of the different samples showed that 80% of
      them were contaminated in the areas of Kaolack and Diourbel. Aflatoxin B1, B2, G1
      and G2 has been detected with a profile of contamination almost identical in the
      both areas. Aflatoxin B1 was prevalent and has been found in over 85% of samples.
      Mean contents of this mycotoxin (the most dangerous toxin) is about 40 ppb, value
      widely superior to allowable specifications.

PMID- 11957286
TI  - [Cancers in the scars of thermal burns (apropos of 67 cases)].
AB  - Burns are very frequent. Skin cancer on burns scars are one of the known
      complications. The mechanisms and the risk factors of this disease are not very
      well known. To review the risk factors and the mechanisms of transformation of
      burn scars into cancer, we analyzed 67 retrospective cases of Marjolin's ulcer to
      describe the epidemiological features of the disease in our practice and identify
      the factors of relapse. Our patients are young (means age 41), mainly male (54%),
      with disease localized on arms and legs (88%). The initial burn was from flames
      (54%), charcoal or hot cooking oil (19.5%) and never from ionizing radiation. It
      was never a superficial burn and covered from 4 to 37% of the body surface (mean
      14%). The initial treatment was medical in only 9% of cases and ended with 85% of
      complete healing. After 4 to 67 years of evolution, 95% of re-ulceration
      occurred. Abnormal lymph node and distant metastasis were diagnosed in
      respectively 68 and 7% of the cases. Amputation and groin dissection were
      respectively done in 63 and 50%. One third of patients were lost during the
      follow up. 25% of the cases are still alive and free of disease. We found 30% of
      local recurrence and 17.5% of regional recurrence. By univariate analysis we
      found that the factors significantly associated to loco-regional relapse are:
      male status (p = 0.0327), burns by cooking oil (p = 0.0118), lack of treatment
      during initial burn (p = 0.0001), sclerous scar (p = 0.0281), supra regional
      lymph nodes (p = 0.028) lack of treatment during re ulceration (p = 0.0308).
      Squamous cell carcinomas on burn scars are rare diseases and of bad prognosis.
      Mainly associated to domestic accidents they frequently occur on limbs and arms
      on an articulation. Metastasis is not frequent. Conservative treatment is
      associated with 30% of recurrence. In our practice, the relapse risk factors are
      male status, burns by cooking oil, lack of treatment during the initial burn,
      sclerous scar, supra regional lymph nodes, lack of treatment during re
      ulceration.

PMID- 11957287
TI  - [Effect and mechanism of action of Tinospora bakis roots on biliary secretion
      using in vivo models].
AB  - The aim of this study is to determine the choleretic properties of lyophilized
      aqueous extract of Tinospora bakis roots. For thus, we have used healthy and
      cholestatic Wistar rats. After administration of the extract (4 mg/100 g of
      weight) biliary flow, biliary acids flow, biliary glutathione and glucose
      concentrations were measured by specific methods. Comparative results between
      treated rats and non treated rats show: For healthy rats: a significant increase
      of biliary flow, biliary acids flow in the group of treated rats versus non
      treated healthy rats. There were no significant difference in the glutathione and
      glucose concentrations. For cholestatic rats: we noted also significant increase
      of biliary flow, biliary acids flow and glutathione concentration in the treated
      rats group. These results suggest that Tinospora bakis has a choleretic effect in
      vivo which depends on biliary acids and/or glutathione concentration.

PMID- 11957288
TI  - [Cancers of the larynx: what therapeutic strategy to use in Senegal?].
AB  - The technical method's deficiency limits the respect of therapeutic principles of
      cervico-facial oncology in our practice. In a period of 16 years, 116 patients,
      aged of 24 to 81 years, sex male in a majority have had laryngectomy for extended
      cancer. In 88% of cases total laryngectomy has been realized and in 12% of cases
      a partial laryngectomy has been realized. In 101 patients, 87%, a neck dissection
      have been associated to the laryngectomy. The post operative radiotherapy have
      been realized in 51 patients. The immediate results are marked by the unexpected
      arrival of pharyngeal fistula in 34 patients. 7 cases of death have been noticed.
      The global survival have been 35% in 3 years and 30% in 5 years. The fatal cases
      have been loco-regional cases and occur during the 18 first months. The surgery
      option, which is our choice, must be maintained and the neck dissection more
      vigorous.

PMID- 11957289
TI  - [Simultaneous treatment of benign prostatic hypertrophy and inguinal hernia: an
      old procedure revisited].
AB  - The association of benign prostatic hyperplasia (BPH) and inguinal hernia still
      pose the problem of the chronology of their repair. Indeed, first hernial repair
      without removing the cervicoprostatic obstruction exposes to a high rate of
      recurrence due to the dysuria. The objective of this work was to report our
      experience about the simultaneous cure of the BPH and inguinal hernia. We have
      performed a retrospective study including a non consecutive series of 92 patients
      presenting both BPH and inguinal hernia. Studied parameters was age, occupation,
      clinical symptoms, the procedure and operative continuations. Mean age was 70.22
      years old, range from 57 to 90 years old. Past history of inguinal hernia repair
      was found in 18.5%. 19.13% had hernial recurrence while 6.5% had contralateral
      hernia. Main clinical features were inguinal mass (43.5%) and acute urinary
      retention (11.9%). The average weight of prostatic tumor was 87.1 g. Surgery was
      performed under spinal anaesthesia in 96.8%. All patients underwent suprapubic
      transvesical prostatectomy. Hernial repair was done according to Bassini
      procedure in 82.6%, Mac Way procedure in 14.2% and Forgues procedure in 3.2%. The
      overall morbidity rate was 15.2%. The hernial recurrence rate was 7.6%. There was
      no postoperative mortality. The simultaneous repair of BPH and inguinal hernia
      offers some advantages. First of all, it reduces considerably the anaesthetic
      risk owing to the importance of cardiovascular diseases in aging patients. On and
      other hand, the low recurrence rate of the hernia and the substantial savings are
      adjunct advantages. We conclude that simultaneous repair of BPH and inguinal
      hernia is simple, safe and economic.

PMID- 11957290
TI  - [Our experience with laminectomy in the treatment of spinal cord disease caused
      by cervical arthrosis: apropos of 42 cases].
AB  - Cervical spondylotic arthRosis may lead to a myelopathy and the question which
      can rise is: posterior surgical decompression is adequate regarding the others
      surgical technics discussed? In this paper the authors describe the postoperative
      results of 42 patients who have been operated on by laminectomy from 1971 to 1995
      at Fann Hospital in Dakar. The median age was 42 years and the median delay
      between the onset of neurological disorders and operation was 5.9 months. All
      patients showed symptoms of spinal cord and root disturbances. Neuro-imaging
      studies with plan X-rays and myelography reveal arthrosis and the impact of this
      arthrosis on nervous system. With a follow up of 6 months we found a mortality
      rate of 4.7% (two cases of death), 66.8% of good results and 28.5% of fail.
      Eighteen months post surgery results were respectively 52.3% and 45.7% of good
      and poor results. The complications of the laminectomy were peri operative
      hemorrhage (19%); sepsis (21.4%); spine cord traumatic injuries (9.5%)
      spondylolisthesis (4.7%). Laminectomy has been found to improve "spine syndrome";
      paresthesia; fasciculations, and sensory deficits. Also three level laminectomy
      and surgery which can take place before six months are good prognosis factors.
      The authors stressed on laminectomy because of our low medical care situations
      particularly that no other surgical procedures through the modern literature
      leads to better results.

PMID- 11957291
TI  - [Description of a case of Cacchi Ricci disease associated with
      hyperparathyroidism in the setting of multiple endocrine disease].
AB  - The authors present a case of a 36 years old woman applied to them for a follow
      up of sponge kidney disease and in whom they discovered a primary
      hyperparathyroidism. Further investigations discovered a medullary thyroid
      carcinoma. So this patient present multiple endocrine neoplasia (MEN) type 2A
      confirmed by microscopic and genetic analysis. This observation enlarged the
      discussion upon the nature of the relationship between kidney disease and primary
      hyperparathyroidism. Elsewhere it recommended to check systematically genetic
      markers of MEN type 2A if there is an association with sponge kidney disease and
      primary hyperparathyroidism.

PMID- 11957292
TI  - [Fernand Widal syndrome: apropos of 2 cases].
AB  - The Fernand Widal syndrome combines a nasal polyposis, an asthma and aspirin
      sensitivity. It remains a nosological entity often unrecognized because of the
      trivialization of aspirin in-take on the one hand the other its etiopathogenesis
      which has not yet been clarified because of the inhibition of the cyclo
      oxygenase. In actual fact the aspirin molecule has yet to reveal all its secrets
      (advantages and disadvantages). We report 2 cases of Fernand Widal syndrome
      observed in 2 women in their thirties with a notion of atopy in one at the
      Pneumophtisiology clinic at the Fann University Hospital in Dakar. The confirmed
      diagnosis was based on oral provocative test in addition to suggestive clinical
      signs which emphasize the classical triad with a chronological appearance more or
      less typical. The best treatment could combine inhaled corticotherapy,
      nasalization of sinus cavities, antihistaminics, no aspirin in take and educating
      the patient.

PMID- 11957293
TI  - [Sharp syndrome complicating pulmonary tuberculosis: apropos of a case].
AB  - This study concerns a case-report about a 28 year old Senegalese woman suffering
      from a SHARP syndrome complicated by a bilateral bacillary pulmonary
      tuberculosis. The prevalence of this disease is underestimated but a female
      predominance is often reported. The mechanisms of this disease strongly depends
      upon the context in with it occurs. The diagnostic has been established by the
      ALARCON SEGOVIA criteria including clinical symptoms (Raynaud phenomenon, puffy
      fingers and myalgia) and biological features such as high positive
      immunofluorescent reactivity revealing the presence of anti RNP antibody at a
      level superior to 1/1000. The subsequent development figure of the disease
      emphasizes: persistence of polymyositis pattern revealed by higher limbs
      localized myalgia involving the thighs and symptoms of lupus including alopecia
      and glomerulonephritis remaining of the mixed characteristic comparable to the
      cases published in the literature. appearance of a bilateral bacillary pulmonary
      tuberculosis with a severe involvement of the right lung. The treatment composed
      by anti inflammatory and antituberculosis drugs lead to an early improvement of
      the clinical symptoms associated to a rapid cleaning of radiological
      manifestations. Sequelae were represented by cavities detected in the right lung
      and related to the pharmacological effects of corticosteroid drugs.

PMID- 11957294
TI  - [Immunologic thrombopenic purpura associated with an autoimmune hemolytic anemia
      or Fisher-Evans syndrome: apropos of a case].
AB  - We report one case of thrombocytopaenia purpura associated with an auto-immune
      haemolytic anaemia (positive erythrocyte Coombs test) or Fisher-Evans syndrome,
      found in a child aged 6 and a half years. Etiopathogenic, clinical, therapeutic
      as well as evolutive aspects are discussed. Response to corticoids is
      satisfactory in case our patient, in opposite to most cases described in the
      literature.

PMID- 11957296
TI  - [Anatomophysiologic and clinical study of the association of epilepsy and
      Parkinson's disease: apropos of 2 cases].
AB  - The authors described the first cases in Senegal (West Africa) of the association
      Parkinson's disease and epilepsy. Almost studies on this feature, stressed on
      their different pathophysiology basis epilepsy is related on excess of neuronal
      excitation, and Parkinson disease is an expression of lack of motor
      neuromodulation. The diagnosis has been done because of the coming out two
      seizures in the year on two patients one 59 years old and the other 70 years old
      experiencing Parkinson disease well documented before and treated. Biological
      study, ultrasonography and Doppler, CT Scan lead to rule out a vasculopathy. Good
      outcome with antiparkinsonian and anticonvulsant medications confirm the
      diagnosis.

PMID- 11957295
TI  - [Crusted scabies in Dakar apropos of 11 cases seen in a year].
AB  - We reported 11 cases of crusted scabies observed during one year in our
      department. The mean age of the patients was 33 years with extremes at 14 and 49
      years. The sex ratio was 1,2. HIV infection was the most common associated
      disease (45% of the patients). Ten patients had been treated with Ivermectin (200
      micrograms/kg). The drug was efficient and well tolerated. For these reasons, we
      recommend to use Ivermectin as a drug of choice in the treatment of crusted
      scabies.

PMID- 11957297
TI  - Fine needle aspiration cytology of breast lesions: a clinicocytologic review of
      1211 cases.
AB  - Fine needle aspiration (FNA) is a widely accepted cytologic technique for the
      early diagnosis of palpable breast lesions. Early diagnosis and treatment of
      benign and malignant breast lesions in turn are associated with increased chance
      of long term survival. Clinical data and results of fine needle aspiration done
      at the Department of Pathology in Tikur Anbessa Hospital between January 1991 to
      December 1994 were reviewed to study the cytologic features of breast lesions and
      to elucidate the clinical use of fine needle aspiration. A total of 9,946 fine
      needle aspirations were done in the department, out of which 1,211 (12.2%) were
      from breast lesions. Results from breast lesions were reported as: malignant,
      benign suspicious and unsatisfactory. Repeat aspiration was performed for all
      unsatisfactory cases. Fine needle aspiration of the 1,211 breast lesions in the
      four year period revealed 255 (21%) malignant, 901 (74%) benign, 15 (1.2%)
      suspicious and 40 (3.3%) unsatisfactory cases. The malignant lesions ranged from
      small, mobile, firm nodules measuring 4 cm to fixed ulcerated and fungating mass,
      measuring 20 cm or more. The benign lesions were small and mobile, measuring from
      2 cm to 6 cm, mostly fibroadenoma (38%). Biopsy result was found for 20 patients.
      Out of these 14 were benign lesions and 6 were malignant lesions, confirmed by
      surgical biopsy. The mean age of patients with malignant lesions was 43 years
      (range: 24 to 80 years), while it was 27 years (range: 15 to 50 years) for those
      with benign lesion. There were 1132 (93.5%) females and 79 (6.5%) males. Fine
      needle aspiration diagnostic technique is recommended to be widely introduced
      into the health system of Ethiopia in order to ensure timely diagnosis of benign
      and malignant breast lesions. Furthermore a properly designed study will be
      beneficial to elucidate the cytologic and clinical characteristics of breast
      lesions in Ethiopian setting.

PMID- 11957298
TI  - A case-control study on determinants of rickets.
AB  - A case-control study on rickets was performed on 156 cases and 307 controls
      admitted to Birla pediatric wards, Yekatit 12 Hospital. The following factors
      were significantly (p < 0.05) associated with diagnosis of rickets in univariate
      analysis: male gender, being a twin, abnormal birth weight, malnutrition, higher
      birth order, higher number of siblings, having a caretaker who is not the mother,
      lower education of the caretaker, having a caretaker who is not housewife, and
      with protective effect, exposure to sunshine (in number of days per week,
      duration of daily exposure in minutes, and not wearing clothes during exposure).
      In multivariate analysis, the following factors remained independently associated
      with diagnosis of rickets in children: being a twin (OR = 5.86, 95% CI = 1.40
      24.50), history of high birth weight (OR = 8.94, 95% CI = 2.30-34.70), moderate
      and severe malnutrition (OR = 5.64, 95% CI = 2.30-13.80 for severe malnutrition
      when compared to normal weight), having the grand mother as caretaker (OR =
      19.80, 95% CI = 3.70-104.70), and with protective effect, exposure to sunshine
      (OR associated with an increase of one day of exposure per week = 0.65, 95% CI
      0.55-0.77; OR associated with daily exposure of more than 30 minutes, when
      compared to less than 15 minutes = 0.24, 95% CI = 0.09-0.64; and OR associated
      with being nude while exposed to sunshine = 0.32, 95% CI = 0.14-0.73). There was
      no significant difference between cases and controls in marital status or
      religion of the caretakers.

PMID- 11957299
TI  - Characterization of Candida albicans isolates from the oral cavity of HIV
      positive patients.
AB  - Characterization of Candida albicans isolates from the oral cavity of Ethiopian
      Human Immunodeficiency Virus (HIV)-positive patients and HIV-negative individuals
      was undertaken. After identification of isolates using conventional methods and
      determination of carbohydrate assimilation profiles, serotyping was performed by
      slide agglutination with the Iatron IF6 serotyping system. Sensitivity of the
      isolates to 5-Fluorocytosine (5-FC) was assessed using the broth macrodilution
      method. There was no difference in phenotype, by any of the three methods used,
      between the HIV-positive and HIV-negative individuals. Serotype A was found to be
      dominant in strains isolated from both HIV-positive (34/40 = 85%) and HIV
      negative (17/20 = 85%) study subjects. These data suggest that the C. albicans
      strains causing oral candidiasis in patients with HIV infection are identical to
      the commensal ones found in healthy individuals.

PMID- 11957300
TI  - Skin diseases seen in Kazanchis health center.
AB  - Studies concerning the prevalence of skin diseases and the general dermatologic
      services in Ethiopia are limited. A total of 7760 patients with 9725
      dermatological diseases were seen by a dermatovenereologist from September 1995
      to August 1996 at Kazanchis Health center in Addis Ababa. Male to female ratio
      was 1.01:1.00. Three thousand eighteen (31.0%) of the total 9725 cases had prior
      evaluation by other health personnel, including doctors (but not dermatologists).
      Out of these cases, 2720 (90.1%) were misdiagnosed and mismanaged. This high
      percentage points to the need for further short-term dermatology training for non
      dermatologists. Bacterial, fungal and viral infections were dominating,
      comprising 19.4%, 18.5% and 6.5% of cases respectively. Infestations (i.e.,
      pediculosis and scabies together) represented 10% of cases. Eczemas contributed
      18.1% of the total cases. Photoallergic dermatitis (4.5%), Pityriasis alba
      (4.4%), urticaria (2.2%), prurigo (2%), benign tumors (1.8%), lichen planus
      (1.6%) and melasma (1.5%) were also quite common.

PMID- 11957301
TI  - Ileosigmoid knotting in Gondar teaching hospital north-west Ethiopia.
AB  - A retrospective analysis of nine consecutive cases of ileosigmoid knotting (ISK)
      that were seen at Gondar hospital from 1993 to 1995 is presented. Ileosigmoid
      knotting is a condition in which the ileum and the sigmoid entangle each other to
      form a knot and become gangrenous. It was found that the clinical features of ISK
      were the results of combination of symptoms and signs of small and large bowel
      obstruction. The presentations were so dramatic that the majority of patients
      deteriorated rapidly with 44% (4/9) developing shock because of gangrene of both
      the ileum and the sigmoid. Abdominal cramps, vomiting and absolute constipation
      occurred in all patients. Five patients were in shock at the time of presentation
      and six had peritonitis at the time of surgery. Release of the knot could easily
      be attained by needle deflation of the sigmoid colon. Hartman's procedure with
      resection of the sigmoid and ileotransversostomy by closing the distal viable
      stump of the ileum is recommended. Four patients out of the nine patients died.

PMID- 11957302
TI  - Men's knowledge, attitude and practices of family planning in north Gondar.
AB  - This community-based cross-sectional study assessed the perceptions and practices
      of 832 men on family planning in North Gondar, Ethiopia, in June 1995. Sixty one
      percent of men knew at least one method of family planning (FP) and 64.3% of them
      approved the use of FP. Forty one percent of these said that only women should
      use contraception. Involvement of couples on the choice of family planning
      methods and desired number of children in the family was approved by 58.3% of
      men. Half of the men did not support nulliparous women of any age using
      contraception. The mean +/- SD desired life-time children was 6.7 +/- 3.5. Only
      47.2% of the study participants had heard about condoms. Misconceptions and
      negative attitudes towards condoms prevailed among men. Only 23.9% of married men
      have discussed family planning with their wives. Overall, 10.6% of men have ever
      used condoms in the past, and 6.1% are currently using condoms. Only 39.3% of
      current non-users of FP are planning to use FP in the future. Educational status
      was positively associated with higher awareness, favourable attitude and practice
      of family planning (p < 0.00001).

PMID- 11957303
TI  - Teratoma of the neck in a newborn: case report.
AB  - Teratomas in the neck are rare neoplasms. Existing or potential airway
      obstruction is usually the main concern in acute management of these patients. A
      first case of cervical teratoma is described in an Ethiopian premature neonate
      born to an 18 year-old primigravida. The clinico-pathological features, including
      autopsy findings, are reviewed. Perinatal asphyxia secondary to huge neck
      teratoma is considered as the likely cause of death.

PMID- 11957304
TI  - Amodiaquine: the exempted antimalarial drug in Ethiopia.

PMID- 11957305
TI  - The low birth weight infant in the Ethio-Swedish Children's Hospital, Addis
      Ababa.
AB  - All low birth weight infants admitted to the neonatal unit of the Ethio-Swedish
      Children's Hospital (ESCH), Addis Ababa from September 1995 to August 1996 were
      followed until discharge. There were 604 babies with birth weight of less than
      2,500 grams and 198 of them died in the hospital making the low birth weight
      mortality rate of 32.8%. More than 90% of these babies were admitted to the unit
      with body temperature of less than 36.5 degrees C irrespective of their birth
      places. Gestational age, birth weight and presence of mother in the neonatal unit
      had significant role in determining survival of the low birth weight infants.
      Prematurity related conditions were the most common causes of death followed by
      infection of the unit. Recommendations are made to improve survival rates of the
      low birth weight infants in Addis Ababa.

PMID- 11957306
TI  - Pattern of histopathologic diagnosis of lymph node biopsies in a teaching
      hospital in Addis Ababa, 1981-1990 G.C.
AB  - To determine the pattern of diseases that are responsible for lymph node biopsy,
      a retrospective study was carried out by reviewing daily register and pathologic
      reports for surgical biopsy specimens for the year 1981-1990 in the Department of
      Pathology, Medical Faculty, Addis Ababa University. Among 33,924 biopsy specimens
      3,396 (10%) were lymph node biopsies (1,378 females, 2018 males). The results
      showed that 57% were cervical, 15.17% axillary and 8.7% inguinal lymph nodes. The
      three main causes of lymphadenopathy were tuberculosis (47.8%), reactive
      lymphadenopathy (26.3%) and malignant lesions (19.8%). In general this study has
      shown that the majority of lymphadenopathies in patients under 40 years of age
      are mainly due to tuberculosis and non specific (reactive) lesions and we think
      this may serve as a basic information for clinicians in their daily activities.

PMID- 11957307
TI  - Kellersberger Memorial Lecture 1998: Nerve Damage in Leprosy: a problem for
      patients, doctors and scientists.
AB  - There are interesting challenges in leprosy right now. The last fifteen years
      have seen the world-wide implementation of multidrug therapy with tangible
      benefits for patients and doctors. Paradoxically this success has revealed how
      much we still need to understand about leprosy nerve damage. For patients it is
      imperative that nerve damage is detected at an early stage when damage is still
      reversible. They need effective education to prevent the development of
      disability and to minimise the social and economic effects of nerve damage. For
      doctors and paramedical workers nerve damage needs effective treatment. We need
      to use current treatments effectively and also develop new treatments. This
      lecture looks critically at the pathology, detection and treatment of nerve
      damage, reviewing our present knowledge and looking to future developments.

PMID- 11957308
TI  - Studies on enteric campylobacteriosis in Tikur Anbessa and Ethio-Swedish
      children's hospital, Addis Ababa, Ethiopia.
AB  - Between February 1992 and January 1993 different Campylobacter spp. were isolated
      from 86 (13.7%) of 630 patients with diarrhoea at Tikur Anbessa and Ethio-Swedish
      Children's Hospital, Addis Ababa, Ethiopia. In the same study population,
      Shigella spp. were found in 11.7% and Salmonella spp. in 3.8%. Campylobacter spp.
      were found in all age groups, but the majority were isolated from children less
      than five years of age (68.6%). Only 2 (0.9%) of 220 controls had campylobacter
      in their stools. Of the campylobacters that were differentiated at species level,
      Campylobacter jejuni accounted for 82.4% and Campylobacter coli for 17.6% of the
      isolates. Yersinia enterocolitica was not isolated from any tested stool
      specimen. More patients (53.1%) presented for investigation of diarrhoea during
      the months of April through July than during other parts of the year but there
      was no significant difference in the frequency of isolation of the three enteric
      pathogens studied during this period as compared to other months of the year. In
      12 of the patients infected with Campylobacter spp., Shigella spp. or Salmonella
      spp. was concomitantly isolated from their stools. The most common symptoms and
      signs in both adults and children were watery diarrhoea in 82.4%, low grade fever
      in 78.4% and frequent vomiting in 45.9%. Dehydration ranging from mild to severe
      was observed in 25.4% of the 55 children with campylobacter infections. Of the 55
      children 67.2% had signs of malnutrition and most of them (47.2%) were
      underweight. This study indicates that Campylobacter spp. are an important cause
      of diarrhoea both in adults and children in Addis Ababa, and should be considered
      routinely in the diagnosis of patients with diarrhoea.

PMID- 11957309
TI  - Preliminary experience with endoscopic retrograde cholangiopancreatography in
      Ethiopia.
AB  - This study was undertaken to evaluate the outcome of diagnostic endoscopic
      retrograde cholangiopancreatography and to increase the awareness of physicians
      practicing in Ethiopia about the procedure. Between April 1993 and October 1997,
      47 patients underwent endoscopic retrograde cholangiopancreatography at Tikur
      Anbessa Hospital, Addis Ababa. Cholestasis, postcholecystectomy syndrome and
      abdominal pain with intermittent jaundice accounted for 91% of the indications.
      The success rate of endoscopic retrograde cholangiopancreatography was 81%.
      Cholestasis provided the highest diagnostic yield followed by postcholecystectomy
      syndrome and abdominal pain with intermittent jaundice. The endoscopic retrograde
      cholangiopancreatography finding was normal in 18% of cases. The commonest
      abnormal findings were gall stones (45%), biliary strictures (16%) and pancreatic
      carcinomas (11%). Using ultrasonography and endoscopic retrograde
      cholangiopancreatography, choledocholithiasis was diagnosed in three (21%) and 13
      (93%) cases, respectively. The endoscopic retrograde cholangiopancreatography
      diagnosis of choledocholithiasis was confirmed at surgery in all but one patient.
      Acute cholangitis and asymptomatic elevation of serum amylase and/or lipase were
      noted in three (6%) and four (9%) cases, respectively. Endoscopic retrograde
      cholangiopancreatography is generally a safe diagnostic modality and should be
      used more frequently for the diagnosis of biliary and pancreatic diseases.

PMID- 11957310
TI  - An in-vivo study of falciparum malaria sensitivity to Chloroquine in unstable
      malaria endemic area of central Ethiopia.
AB  - The role of Chloroquine as a first line drug to treat P. falciparum is almost
      universally becoming questionable. This study was conducted in one of the
      country's unstable malaria endemic area, North Shoa with the objective of
      assessing the in-vivo treatment efficacy of Chloroquine to falciparum malaria
      using the standard WHO 14 days treatment response monitoring guideline. A total
      of 427 patients were followed among which 87.8% showed treatment failure. This
      was more pronounced in children than in adults (Chi-square for trend = 8.16; P <
      0.01). Clinical presentation with high grade fever on day 0 was found to be more
      predictive of treatment failure in children (OR = 2.06; 95% CI = 1.26, 3.36; P <
      0.005). Tendency to remain febrile on subsequent follow up days was also more
      observed in children compared to adults. Treatment failure was further associated
      with high Parasite Density Index (PDI) on day 0 in all age groups (OR = 1.99; 95%
      CI = 1.04, 3.83; P < 0.05). Supplemented with large scale sensitivity studies, it
      is high time that switch to alternate drugs needs due consideration by policy
      makers.

PMID- 11957312
TI  - Rheumatic heart disease among school children in Addis Ababa City: awareness and
      adequacy of its prophylaxis.
AB  - One of the objectives of this large scale cross-sectional study of school
      children of the Addis Ababa city was to assess the status of rheumatic heart
      disease (RHD) prophylaxis among rheumatic heart disease patients identified
      during the survey. Awareness about the presence of the illness in those affected
      and reasons for poor coverage, when detected, were also assessed. Sixty of the
      9388 school children surveyed were found to have rheumatic heart disease. On
      interviewing parents of the children with rheumatic heart disease, ten
      acknowledged being informed of their children's cardiac illness. Of these
      parents, 15% (or 9/60) had some idea that their children had heart disease
      related to some form of infection. However, only two of the nine (22%) children
      whose parents had some idea about their disease were on regular monthly
      benzathine penicillin prophylaxis in the previous 12 months preceding the
      interview. Three (33%) of the nine children had six or fewer injections in the 12
      months preceding the interview. The remaining 4 parents (44%) reported that their
      children took treatment that included injections only at the time of initial
      diagnosis several years earlier and had not had any follow up since then. Their
      reasons for not seeking medical care for their children included lack of
      information on prophylaxis, inability to pay for the treatment and distance of
      the health facilities. The lack of awareness and the extremely low rate of
      regular prophylaxis, therefore, highlight the need for an urgent control
      programme that takes active case detection, treatment access and health education
      into consideration.

PMID- 11957311
TI  - Medical and social consequences of tuberculosis in rural Ethiopia.
AB  - An institution based cross sectional study was conducted in June 1996 at a rural
      health centre in South Gonder Administrative Zone of Northern Ethiopia. Interview
      and respective review of medical records of patients were done. A total of 211
      tuberculosis (TB) patients were included in the study, 133 (63%) males and 78
      (37%) females. Majority (79.6%) of patients had pulmonary disease. Clinical
      observation based on symptoms and signs suggestive of tuberculosis was used as a
      sole criteria to prescribe anti-tuberculosis treatment in 54.1% (114/211) of all
      the patients. Acid fast staining of sputum was done for 51.2% (86/168) of the
      pulmonary patients out of whom only 31.4% were smear positive. Social ostracism
      was observed to have been affecting tuberculosis patients and their families to a
      great extent. Divorce rate due to tuberculosis among patients was 29.1% (37/127).
      Patients have reported loss or threat to lose their job. Dietary misconceptions
      were rampant. The TB control activities were ineffective and poorly organised.
      Starting anti-tuberculosis treatment without proper diagnosis was observed to
      have negative consequences on the patients and the control programme. Appropriate
      counselling service along with the medical treatment was provided to patients
      with eventual family reunions. Patients were also organised into local 'TB clubs'
      by their residential locations so as to improve treatment adherence and the level
      of TB awareness among the patients and the community. It is strongly recommended
      that the political system and health authorities of Ethiopia should have to give
      much more attention and commitment to the TB control activities in Ethiopia.

PMID- 11957313
TI  - Malignant tumours at Yirga Alem Hospital.
AB  - A ten year (January 1986 to December 1995) retrospective analysis of biopsy
      results of patients seen at Yirga Alem Hospital was conducted. There were 841
      histologically certified cancers (410 males and 431 females). The mean and the
      median ages were 42.1 and 42 years, respectively. Skin and lymphoreticular
      cancers were the commonest in males while cervical cancer was by far the
      commonest in females followed by skin, breast and ovarian cancers. In the
      paediatric age group, soft tissue sarcoma occurred most often followed by
      retinoblastoma and lymphoma. The results of the study were similar to that of
      previous studies done in Ethiopia. The biases that might have influenced the
      results of the study are discussed. A hospital cancer registry is recommended to
      generate more reliable data.

PMID- 11957314
TI  - Rapid diagnosis of severe malaria based on the detection of Pf-Hrp-2 antigen.
AB  - Blood samples collected from 34 patients with severe malaria who were involved in
      antimalarial treatment studies were tested with rapid dipstick assay (Rapid Test
      Malaria, RTM from Quorum Diagnostics Inc., Vancouver, BC, Canada), based on the
      detection of Histidine Rich Protein (HRP-2) of Plasmodium falciparum. This was
      compared with the conventional Giemsa stained thin and thick blood smears. The
      study was done from March 1998 to May 1998, at the Basic Research Laboratory of
      the Faculty of Medicine, Addis Ababa University. Comparable number of patients (n
      = 32) with various diagnosis other than falciparum malaria were used as controls.
      The rapid dip-stick assay was positive in 31 among 34 of the severe malaria cases
      with sensitivity of 91.2%, specificity of 93.7%, positive predictive value (PPV)
      of 93.9% and negative predictive value (NPV) of 90.9%. The three cases missed by
      the RTM, had parasitemia of 66,000, 44,000, and 40,000/microL of blood which
      might be due to genetic heterogeneity of the HPR-2 expression. Among the
      controls, there were 2 false positive cases which may be as a result of
      persistent HPR-2 antigen after the clearance of peripheral parasitemia. The dip
      stick method is a very quick, sensitive and specific diagnostic tool with limits
      of detection comparable or better than those provided by the light microscopy.
      The simplicity of the technique makes this method more applicable in the resource
      deprived laboratories of developing countries provided the kit is affordable for
      large scale use.

PMID- 11957315
TI  - Increasing incidence of resistance to antimicrobials in Sidamo.
AB  - This study compares the prevailing sensitivity of bacterial isolates to common
      antimicrobials during the two-year 1985-87, 1990-92 and 1996-97 periods at Yirga
      Alem Hospital in southern Ethiopia. All specimens were from patients attending
      the hospital. We studied 1371 specimens, 337,671 and 363 specimens from the
      periods 1985-87, 1990-92 and 1996-97, respectively. The study confirms earlier
      observations of widespread resistance to commonly used antibiotics. Significant
      increases in the rate of resistance during this thirteen-year period were
      observed for Neisseria gonorrhoea against erythromycin, trimethoprim
      sulphamethoxazole and tetracyclines, for Escherichia coli against ampicillin and
      trimethoprim-sulphamethoxazole and for Proteus species against ampicillin. We
      observed a decrease in the prevalence of resistance for Klebsiella and Proteus
      species against chloramphenicol.

PMID- 11957316
TI  - Unusual presentation of rectal carcinoma in a young woman.
AB  - Advanced rectal carcinoma usually presents with rectal bleeding, tenesmus or
      alteration in bowel habits. Secondary deposits in the inguinal lymphnode is
      generally an indication of advanced disease. We report unusual presentation of
      advanced rectal carcinoma in a 23 year-old female patient who came presenting
      with symptoms of left inguinal lymphadenopathy and left leg swelling. There were
      no symptoms related to local effects of rectal carcinoma. First the patient was
      treated as a case of deep venous thrombosis. Fine needle aspiration biopsy
      provided the first clue to the nature of disease. To the best of our knowledge
      such unusual presentation of advanced rectal carcinoma has never been reported in
      Ethiopia. Rectal carcinoma should be considered in the list of secondary
      adenocarcinoma in the inguinal lymphnodes.

PMID- 11957317
TI  - Neuroleptic malignant syndrome: a case report.
AB  - Neuroleptic malignant syndrome (NMS) is a controversial, relatively rare and
      potentially fatal drug side effect which occurs with the use of neuroleptics and
      other drugs that adversely affect the dopamine system. To our knowledge there has
      been no previous report on NMS from Ethiopia. We present a case here and stress
      the need for early detection of this potentially fatal condition. The case is a
      14 year old manic patient who while under inpatient treatment at Amanuel Hospital
      between November 19, 1997 and February 13, 1998 exhibited fever, muscular
      rigidity, autonomic instability and some laboratory evidences of muscular
      destruction which are said to be typical features of NMS. The patient was
      receiving chlorpromazine until four days prior to the onset of the symptoms when
      haloperidol was added. There was no other physical condition by which these
      clinical features could be explained. The symptoms resolved within 2 weeks by
      simple drug withdrawal and supportive treatment.

PMID- 11957318
TI  - The effects of fabric air permeability and moisture absorption on clothing
      microclimate and subjective sensation in sedentary women at cyclic changes of
      ambient temperatures from 27 degrees C to 33 degrees C.
AB  - The present paper aimed at learning the effects of two different levels of air
      permeability and moisture absorption on clothing microclimate and subjective
      sensation in sedentary women. Three kinds of clothing ensemble were investigated:
      1) polyester clothing with low moisture absorption and low air permeability (A
      clothing); 2) polyester clothing with low moisture absorption and high air
      permeability (B clothing); and 3) cotton clothing with high moisture absorption
      and high air permeability (C clothing). After 20 min of dressing time, the room
      temperature and humidity began to rise from 27 degrees C and 50% rh to 33 degrees
      C and 70% rh over 20 min, and it was maintained for 30 min (Section I); it then
      began to fall to 27 degrees C and 50% rh over 20 min, and it was maintained there
      for 20 min (Section II). The subject sat quietly on a chair for 110 min. The main
      findings are summarized as follows: 1) The clothing surface temperature was
      significantly higher in C clothing than in B clothing during section I, but it
      was significantly higher in B clothing than in C clothing during section II. 2)
      Although the positive relationship between the microclimate humidity and forearm
      sweat rate was significantly confirmed in all three kinds of clothing, the
      microclimate humidity at the chest for the same sweat rate was lower in C
      clothing than in A and B clothing. These results were discussed in terms of
      thermal physiology.

PMID- 11957319
TI  - Interobserver errors in anthropometry.
AB  - To present basic information on the interobserver precision and accuracy of 32
      selected anthropometric measurement items, six observers measured each of 37
      subjects once in two days. The data were analyzed by using ANOVA, and mean
      absolute bias, standard deviation of bias, and mean absolute bias in standard
      deviation unit were used as measures of bias. By comparing the results of the two
      days, the effects of the practice on measurement errors were also investigated.
      Variance was overestimated by more than 10% in five measurements. Interobserver
      error variance and random error variance were highly correlated with each other.
      Measures of the bias were significantly correlated with interobserver and
      especially with random error variances. The interobserver errors were drastically
      reduced on the second day in the measurement items in which the causes of the
      interobserver errors could be specified. It was speculated that even when the
      definitions of the landmarks and measurement items were clear, the ambiguity in
      the practical procedures in locating landmarks, applying instruments, and so on,
      permitted each observer to develop his or her own measurement technique, and it
      in turn caused interobserver errors. To minimize interobserver and random errors,
      the standardization of measurement technique should be extended to the details of
      the practical procedures.

PMID- 11957320
TI  - Female-left and male-right positioning by young Japanese couples.
AB  - I discovered a phenomenon related to nonverbal sex differences in young Japanese
      couples in which the female tends to assume the left side position and the male
      tends to assume the right position (FM tendency) when the couple are walking on
      sidewalks and in parks. As the first step of the present study, some aspects of
      this phenomenon were examined through field observation. In total, 2,827 couples
      (teens and 20s: 1,799; 30s and 40s: 732; older than 50: 296) were examined. The
      following facts were clarified: (1) Couples in their teens and 20s couples showed
      a clear FM tendency, and couples older than 30 did not. (2) The FM tendency in
      couples in their teens and 20s was seen in all places where observations were
      done (street, sightseeing park, shopping center). (3) The FM tendency was seen
      when neither the female nor the male was carrying anything. Each person tended to
      take a position to avoid having any parcel, handbag, or other item between the
      partners. (4) The FM tendency was seen when neither partner touched the other,
      and when both partners reciprocally touched. When only the female touched her
      partner, the FM tendency was especially conspicuous. When only the male did, the
      FM tendency was not seen. As an essential causation of the FM tendency, the
      intention by females to touch their partners by the dominant right hands was
      suggested.

PMID- 11957321
TI  - Subjective duration of every three-year period for 3 to 18 years of age,
      estimated by students.
AB  - Results indicated that both subjective time durations, one day and three years,
      are well described by the normal distribution if the time scale is logarithmic
      rather than linear. A remarkable finding obtained here is that in reference to
      the mean subjective time duration of the junior high school (three years), the
      mean subjective time durations for each of the three-year periods before
      elementary school were significantly longer than unity (about 1.2), and the
      subjective duration of the three year period of the senior high school is
      significantly shorter (about 0.8). When subjects transferred to other elementary
      schools at 6 to 11 years of age, the mean subjective time duration of the periods
      below 11 years of age was much longer, more than 1.3.

PMID- 11957322
TI  - Sleep patterns and sleep disorders among female shift workers in a computer
      factory of Japan.
AB  - Using a repeated questionnaire survey for female workers in a computer factory of
      Japan, consisting of 45 daytime workers and 84 weekly rotating shift workers (of
      whom 40 and 44 were respectively engaged in early-shift work and late-shift work
      during the survey week), the present study aimed to clarify the effects of shift
      work on their sleep patterns and sleep disorders. The time of retiring, time of
      rising, duration of sleep, and self-evaluated sleep quality based on four sleep
      related problems were investigated for four days (Sunday-Monday, Tuesday
      Wednesday, Thursday-Friday, and Saturday-Sunday) in a week. The intergroup
      comparison revealed that the earlier the rising time and the shorter the duration
      of sleep, the lower the sleep quality; the lowest sleep quality was observed in
      the early-shift workers.

PMID- 11957323
TI  - Do majoring subjects affect the morningness-eveningness preference by students?
AB  - Women preferred morningness significantly more than men. Differences in scores
      between both sexes became greater in order of the phase points of 'rising time,'
      'peak of activities,' and 'falling-to-sleep time,' suggesting that oscillator(s)
      of men are more easily free-running than those of women. Women majoring in
      natural sciences or agriculture preferred morningness significantly more than
      women majoring in humanities, economics, or education.

PMID- 11957324
TI  - Growth and residential conditions of a slum community in Colombo, Sri Lanka.
AB  - Based on the authors' fieldwork, this article examined the spatial and
      demographic growth of a slum community in Colombo, Sri Lanka, in association with
      the inhabitants' socioeconomic conditions. In this slum community, which is near
      the industrial and commercial centers and has developed especially since the
      early 1970s, most dwellers are migrants from other parts of Colombo. The increase
      of dwellers resulted in a high-density residential condition, represented by an
      extremely small floor area per person, despite an income level that is not
      extremely low.

PMID- 11957325
TI  - Human aspects of shift work in the developing countries--I: A case study in
      Bangladesh.
AB  - There currently is little information available that allows objective prediction
      of psychosocial risks and benefits associated with the shift work in the
      developing countries. To provide such information, this study assessed possible
      differential effects of fatigue associated with the shift workers' attitude, job
      satisfaction, psychosocial problems, and other difficulties. Data were collected
      from the subjective responses on various scales using questionnaire among sixty
      adult male subjects working on a weekly rotating three-shift system in a shoe
      factory in Bangladesh. The results indicated that shift work is associated with
      negative aspects of disturbing their family, conjugal and social lives, curtailed
      leisure activities, created difficulties in meeting their friends, caused
      irregularity of their mealtime, affected sleep and caused health problems.
      However, the effect is significant only for such feelings of social and family
      aspects, as well as sleepy and lively hood but no significant main effects of
      shift schedule are observed for any of the behavioural and organizational
      context.

PMID- 11957326
TI  - Divided loyalties. Legal and bioethical considerations of physician-pregnant
      patient confidentiality and prenatal drug abuse.

PMID- 11957327
TI  - Punitive damages in lawsuits against nursing homes.

PMID- 11957328
TI  - Physician/hospital liability for negligently reporting child abuse.

PMID- 11957329
TI  - Rural health care now and tomorrow. A symposium introduction and overview.

PMID- 11957330
TI  - Patient safety and medical errors. Implications for rural health care.

PMID- 11957331
TI  - Refrain or reality: a United States rural policy? Implications for rural health
      care.

PMID- 11957332
TI  - Rural America and the digital transformation of health care. New perspectives on
      the future.

PMID- 11957334
TI  - Dracunculiasis. Global surveillance summary, 2000.

PMID- 11957333
TI  - Liability for overprescription of controlled substances. Can it be justified in
      light of the current practice of undertreating pain?

PMID- 11957335
TI  - Meningococcal disease, Chad.

PMID- 11957337
TI  - Dracunculiasis surveillance, Chad.

PMID- 11957336
TI  - Progress towards global poliomyelitis eradication, 2000.

PMID- 11957338
TI  - Rabies vaccines.

PMID- 11957339
TI  - [Personal peculiarities of epileptic patients with depersonalization in the
      interictal period].
AB  - Depersonalization states, expressed in interictal period, were analyzed in 23
      patients. Depersonalization state occurs only in patients with partial complex
      seizures with epileptic focus in the temporal areas of the right hemisphere and
      in the mediobasal frontal areas of the left hemisphere. Also, compared to healthy
      subjects, schizoid personality features by MMPI and Rorshach psychological tests
      were found in these patients. The depersonalization states studied were defined
      as neurotic ones, because they manifested after psychotraumatic situation and did
      not recur after psychotherapy.

PMID- 11957340
TI  - [Neuropsychological functions in individuals exposed to small dose ionizing
      radiation].
AB  - Two groups, including 205 Chernobyl wreckers and 88 staff workers exposed to
      ionizing radiation, were examined. In the former group, radiation doses were
      0.005-0.349 Gy, in the latter one--0.0001-0.011 Gy. An examination was conducted
      according to standard diagnostic neuropsychological tests proposed by A.S. Luria.
      Both groups were found to exhibit deviations of different degree. Memory,
      acoustic-perceptual and, partially, thinking functions were most vulnerable.

PMID- 11957341
TI  - [Clinical importance of EEG changes during the treatment of epilepsy with
      valproate (depakene chrono)].
AB  - In 24 patient with epilepsy in the age fo 6-46 years the EEG was studied before
      treatment and after stabilization of the initial and corrected dozes of valproate
      (depakine chrono). The manual analysis with the formalized quantitative
      estimation of indexes of epileptic activity (El) and computerized mapping of
      spectral power in the main bands of EEG was carried out. In 18 patients remission
      of a half-year and more was achieved. Average El before treatment in all group
      was 15.1 +/- 1.9, on the initial stabilized doze (10-15 mg/kg/day)--4.3 +/- 1.2
      (p = 0.000), at increase of a doze > 15 mg/kg/day, on the average it was not
      revealed of the further change of El. There was significant positive correlation
      between epileptic activity in EEG, expressed by El and number of attacks in the
      patient per one month on the moment of EEG research (r = 0.65, t = 6.58). In 6
      patients with farmacoresistence the index of epileptic activity was significantly
      higher (El = 11.7 +/- 4.3), than in the patients with good effect (El = 1.9 +/-
      0.8, p < 0.002). In data of the computer analysis under influence of depakine
      chrono the reduction of power in all bands and leads was observed, except
      occipital lobes where the increase of alpha-power was observed. This reflects
      reduction of epileptic activity and restoration of normal EEG, which accompanied
      the improvement of social and psychic adaptation. The results of the study
      demonstrate that automated or manual EEG control is important factor of correct
      selection of a valproate doze during treatment, that allows not only to suppress
      effectively the attacks, but on the minimal but sufficient doze to reach
      improvement of psycho-social functioning and to reduce terms of treatment, at the
      expense of control of an unpredictable relapse of attacks.

PMID- 11957342
TI  - [Computer-assisted EEG in epileptic patients treated with intermittent normobaric
      hypoxic therapy in combined treatment of epilepsy].
AB  - The article presents an analysis of bioelectrical brain activity in patients with
      epilepsy during adaptation to intermittent normobaric hypoxia. Before adaptation
      and after the 1st, 4th, 20th adaptation sessions, resting EEG and EEG during
      hyperventilation were registered. By the end of the hypoxic trainings, a
      significant increase of spectral power of the EEG bands was found in resting EEG.
      At comparing bioelectrical activity in the resting condition and during
      hyperventilation, the difference between these indices decreased towards the end
      of hypoxic therapy course. This evidence argues for brain functions normalization
      during hypoxic therapy.

PMID- 11957343
TI  - [Complex evaluation of treatment efficacy in diabetic encephalopathy].

PMID- 11957344
TI  - [Influence of long-term moxonidine (psysiotens) monotherapy on neuropsychological
      status and brain perfusion in elderly patients with arterial hypertension].

PMID- 11957345
TI  - [Spatial organization of bioelectrical brain activity in epilepsy and amenorrhea
      of central genesis].
AB  - The study aimed at modification of co-herent analysis (CA), as a mathematical
      method for EEG data processing for objective evaluation of bioelectric brain
      activity spatial organization in women with epilepsy and secondary amenorrhea of
      central genesis. One hundred sixty one women (30 with epilepsy, 116 with
      amenorrhea and 115 controls aged 15 to 41 years) have been examined.
      Characteristic changes of cortico-cortical inter- and intra-hemisphere relations
      for patients with catamenial (CTM) and noncatamenial (NCTM) epilepsy in different
      menstrual cycle terms were found. The most distinct changes were detected in
      theta-activity analysis. In the beginning of menstrual cycle, the patients with
      CTM epilepsy exhibited higher CA indices in theta-rhythm range in all right
      hemisphere pairs studied. On the contrary, patients with NCTM epilepsy exhibited
      lower CA indices mainly in the right brain hemisphere. alpha-rhythm spatial
      organization analysis in the same patients showed similar correlations, but they
      were better expressed in alpha-rhythm generation zone: in the beginning of
      menstrual cycle CA indices were high in patients with CTM epilepsy and low in
      those with NCTM epilepsy. Comparing to controls, patients with secondary
      amenorrhea of central genesis showed most distinct changes in theta-activity
      towards the CA indices increase in the majority of the leads. In patients with
      epilepsy and amenorrhea, CA indices of right brain hemisphere and intra-central
      temporal lead pairs were lower than in patients with amenorrhea without epilepsy
      by both alpha- and theta-rhythms.

PMID- 11957346
TI  - [Pathological dominant and determinant in pathogenesis of nervous and mental
      disorders].
AB  - The dominant (A.A. Ukhtomsky) and the determinant (G.N. Kryzhanovsky) are
      different working principles and basic mechanisms underlying nervous system
      function in health and disease. The main feature of the dominant is related
      inhibition of other structures or systems. This inhibition provides normal
      functioning of physiological system, which is dominant at the given time. The
      pathology of the dominant relationships consists in insufficient or excessive
      coupled inhibition. The structures which determine and form a corresponding
      functional premise to the efferent system structures for achieving the present
      result play a role of the determinant in physiological system. The role of the
      pathological determinant is performed by hyperactive CNS structure which
      determines a functional state of other structures connected with it and forms,
      along with them, a pathological system underlying the corresponding
      neuropathological syndrome.

PMID- 11957347
TI  - [Brain functional status in patients suffering from hemorrhagic fever with renal
      syndrome].
AB  - EEG mathematical analysis in 59 patients with hemorrhage fever with renal
      syndrome (HFRS) revealed significant changes of bioelectrical brain activity,
      being expressed most distinctly during severe course, in the different stages of
      the disease. Re-convalescents after HFRS severe type showed lower EEG coherence
      indices in all frequency bands that argued for consistency of electric process
      dysfunctions in great brain cortex and might reflect structural brain damage. The
      data obtained exhibit higher informative ness of the EEG mathematical analysis
      not only in the context of differential and diagnostic perspectives but also for
      adequate evaluation of cerebral disturbance expression and their manifestation
      prognosis in the HFRS patients.

PMID- 11957348
TI  - [Methodological approaches to investigation of autonomic nervous system functions
      in young children].
AB  - Techniques for investigation of a functional condition of autonomic nervous
      system in young children--anamnesis questionnaire, a list of basic vegetative
      disorders and screening table for vegetative tonus evaluation--were elaborated.
      These tools have been tested in a longitudinal study of more than 200 children,
      aged 3 months to 5 years, with various psychic disorders, 143 being related to
      high-risk group for schizophrenia, and were proved to be higher informative,
      simpler and more convenient for practitioners.

PMID- 11957349
TI  - [Acetylcholine receptor antibodies in patients with myasthenia].
AB  - Acethylcholine receptor (AChR) antibodies in patients with myasthenia were
      studied for the first time in Russia with radioimmuno-assay application.
      Seronegative result (antibody titer lower than 0.2 nmol/l) was obtained for 33%
      of the patients and seropositive one (antibody titer higher than 0.2 nmol/l)--for
      67%. AChR antibodies level varied from 1.9 to 115.0 nmol/l. The AChR antibodies
      were found more frequently and in higher titers in women than in men. Correlation
      analysis revealed strong correlation between AChR antibodies level and severity
      of myasthenia.

PMID- 11957350
TI  - [CTG-repeat analysis of myotonin protein kinase gene in Bashkortostan patients
      with myotonic dystrophy].
AB  - A DNA analysis of 72 patients from Bashkortostan clinically diagnosed with
      myotonic dystrophy and 54 their family members was conducted. CTG-repeat
      expansion in the myotonin proteinkinase gene was found in 67 (92%) patients and
      12 their relatives without clinical symptoms of the disease at the moment of
      examination. A correlation between the most distinct clinical symptoms and CTG
      repeat number has been studied. A CTG-repeat expansion in generations was
      compared to that in sib pairs with myotonic dystrophy. In 17.6% of the cases, CTG
      repeat number decreased in the following generations and in 11.7% it did not
      change, the percentages being higher than those described elsewhere. In general,
      anticipation phenomenon was confirmed for CTG-repeat in myotonin proteinkinase
      gene.

PMID- 11957351
TI  - [Medical and social characteristics and adaptation of drug abusers].

PMID- 11957352
TI  - [Study of "speech circle" modification and autonomic reactions in stuttering].

PMID- 11957354
TI  - [Neuropathological correlates of movement disorders].

PMID- 11957353
TI  - [The influence of vegetative status of patients with neurological signs of
      cervical osteochondrosis on manual therapy efficacy].

PMID- 11957355
TI  - [Huntington's chorea: pathogenesis and new treatment approaches].

PMID- 11957356
TI  - [Psychogenic pseudo-epileptic seizures].

PMID- 11957357
TI  - [Autonomic system disorders in patients with myasthenia gravis].
AB  - Using a set of techniques, segmentary and nonsegmentary autonomic nervous system
      compartments were studied at rest and under stress. Parasympathicotonia, on the
      background of general deficit of ascending nonspecific brain activity, was found
      to characterize myasthenia in general. A decrease of nonspecific brain activity
      level is combined with elevated anxiety. However, one may distinguish a
      generalized type of the disease by the presence of dissociation of the autonomic
      nervous system compartments due to sympathicotonia.

PMID- 11957358
TI  - [The National Institute of Health: 1917-2002].

PMID- 11957359
TI  - [Snake bites accidents in Yopal and Leticia, Colombia, 1996-1997].
AB  - Snakebites produce notable morbidity and mortality in the Amazonian and Orinocan
      regions of Colombia. A review was undertaken of 56 snakebite cases sent to
      hospitals in Leticia (Amazonas) and Yopal (Casanare) between September 1996 and
      June 1997. Of the total, 57% of the bites occurred in Leticia, 54% in men. The 14
      to 44 year-old age group was most compromised (41%). Most encounters occurred in
      forests and open fields between 17:00 and 18:00 hours (57%). Nearly all bites
      were located on legs and feet (82%). One death occurred in Yopal; 3 fasciotomies
      and 2 amputations were performed. Snakebite incidence occurred with highest
      probability during evening hours. Although antibiotics are in general use, minor
      infections (16%) were frequent.

PMID- 11957360
TI  - [Determination of total phenylalanine and galactose from a sample of dry blood on
      paper filter: its application on neonatal screening].
AB  - Neonatal screening programs for metabolic disorders are recommended especially
      for phenylketonuria and congenital hypothyroidism. The present study was designed
      to adapt, develop and evaluate a SUMA method for total galactose (Gal) and
      phenylalanine (Phe) measurement on filter paper blood specimens. A single 5 mm
      disk with blood was deproteinized with methanol-acetone and eluted with distilled
      water. Ten microliters of the extract was transferred to one well of a
      ultramicroELISA plate, and the reaction solution was added to determine Phe
      level. The remaining extract was used for the GAL determinations. The method
      showed good linearity in a 0-50 mg/dl concentration range for Phe and 0-60 mg/dl
      for Gal. The detection limit was 0.14 mg/dl for Phe and 0.9 mg/dl for Gal.
      Reproducibility was assessed with filter paper blood specimens containing Gal and
      Phe at low, middle and high levels. Intraassay coefficients of variation were
      10%, 7.5%, 6.22%, and 8.5%, 7%, 5%, respectively, whereas interassay coefficients
      of variation were 9.54%, 6%, 7% and 6%, 4.6%, 5.6%, respectively. In 1,000
      samples from newborns, four samples of Phe and two samples of Gal showed a
      concentration below the threshold set for each assay. This method provides a
      rapid means to survey for a low incidence disease (i.e., galactosaemia:
      incidence, 1/30,000), in existing phenylketonuria analysis programs, where an
      incidence of 1/10,000), easily justifies the cost of mass screening.

PMID- 11957361
TI  - [Indirect immunofluorescence as a supplementary test for confirming HIV-1
      infection: the experience of the National Institute of Health, 1993-2000].
AB  - A team at the Colombian National Institute of Health (INS) has demonstrated the
      usefulness and suitability of the Immunofluorescent Antibody Test (IFAT) as a
      confirmatory assay for HIV-1. The assay followed a flow chart method recommended
      by the Pan American Health Organization (PAHO) and the Federal Center for AIDS of
      Canada. The specificity of the IFAT assay (IFI-VIH1-INS) for 925 serum samples
      was 100% when compared with two different Western blot (WB) assays. The IFI-VIH1
      INS showed a sensitivity of 61% across 6,137 human sera. Although its specificity
      is excellent, the sensitivity of the IFI-VIH1-INS assay is slightly lower than
      other IFAT assays (41% of 975 samples were indeterminate in both IFAT assays and
      WB tests). After implementation of this assay in more than 6,000 serum samples
      between 1993 and 2000, the INS saved more than Col $340,000,000 or US $170.000 in
      its HIV1 testing program.

PMID- 11957362
TI  - [Control of Chagas disease in blood banks in Colombia].
AB  - The screening programs for the Chagas disease agent, Trypanosoma cruzi, were
      examined in Colombian blood banks and, as a consequence, several procedural
      improvements in the blood bank network were recommended. Screening strategies and
      techniques were examined, as well as the action taken when seropositive donors
      were discovered. From a total of 180 blood banks in 33 departments, 103 banks in
      20 departments answered the survey. The 103 banks collected 291, 105 units of
      blood, corresponding to 66.6% of all units collected in the country in 1997. Of
      these blood units, 99.6% were screened for Chagas trypanosomes; 3,321 (1.2%) of
      287,048 were found positive for anti-T. cruzi. The data were grouped by
      department; geographical differences for seroprevalence rates varied markedly
      between 0% and 12.6%. The most commonly used serological technique was ELISA, but
      only 33.2% of the positive samples for anti-T. cruzi underwent further
      confirmatory testing, mainly through indirect immunofluorescent test. Most
      (95.1%) of the blood banks used basic, internal quality control procedures, and
      73.8% sent positive samples to other laboratories for external quality control.

PMID- 11957364
TI  - [You make the diagnosis].

PMID- 11957363
TI  - [Stability and effect of ingestion on the levels of folate in plasma].
AB  - The physiological demand of folates increases during adolescence, pregnancy and
      lactation due to the rapid growth and anabolic activity during these stages of
      life. The periconceptional deficiency of folates is a risk for the presence of
      neural tube defects. We studied the stability of folates concentration in plasma
      and the effect of ingestion of a breakfast rich in folates on the postprandial
      levels of this micronutrient, up to two hours after food intake. For the
      stability assay the samples were stored protected from light at -70 degrees C and
      analysed at time intervals of 1, 8, 30, 90 and 120 days. The mean folates
      concentration in plasma was higher in postprandial stage (8.9 ng/dl) that in
      fasting (7.9 ng/dl), which represents a statistically significant (p < 0.01)
      increase of 11%. This study confirms that fasting is important in folates
      determination for diagnosis and research purposes to establish deficiency
      prevalence of this micronutrient in a population. Concerning the stability of
      folates concentration, we did not find a significant difference between the
      several time analysis (p > 0.1); this suggests that folates concentrations in
      plasma remain stable under the experimental conditions described.

PMID- 11957365
TI  - [Polymorphism in allergens].
AB  - Allergens are antigens that elicit an IgE-mediated immune response; they
      originate from diverse sources such as pollens, mites, molds, mammal exudates,
      insects and food. Allergenic molecules can contain several antigenic
      determinants, termed epitopes. Allergenic proteins have been discovered with
      polymorphisms, i.e., a mixture of similar molecules with minor variations in
      their amino acid sequences. These are called isoallergens or allergenic variants
      depending on the degree of similarity. Polymorphism may be defined by the
      presence of several alleles of the same gene or as families of related genes.
      Polymorphisms can have an important effect on the epitopes recognized by T
      lymphocytes, monoclonal antibodies and IgE of allergic patients. Individual
      polymorphisms can affect the basal level of allergenicity as well as the cross
      reactivity with other allergens. The use of isoforms with low or total absence of
      IgE binding capacity but with high capacity to stimulate T cell response has been
      suggested as an alternative to the conventional immunotherapy for allergic
      diseases. Standardization of allergenic compounds can be affected by the
      differing proportions of isoforms in allergenic sources from different regions.

PMID- 11957366
TI  - [Modulation of the expression of L-selectin by chemotactic agents and GM-CSF].
AB  - L-selectin is an adhesion molecule with constitutive expression located on the
      membrane of granulocytes, monocytes and lymphocytes. It is involved in the early
      stages of migration of these cells toward either the sites of inflammation or
      lymphoid tissues. After the cells are activated, L-selectin is down-regulated
      with shedding of a soluble fragment. Flow cytometry was used to measure L
      selectin expression levels on the granulocyte surface, after incubation with a
      phorbol esther (PMA), two chemotactic factors (fMLP and LTB4) and a cytokine (GM
      CSF). Under basal conditions, the expression of L-selectin was found in a high
      percentage (95.0 +/- 0.7) of granulocytes; PMA stimulation led to a marked
      decrease in expression (3.2 +/- 0.6). Chemotactic factors also led to a
      significant decrease in L-selectin expression (69.9 +/- 5.0 for LTB4, and 53.70
      +/- 4.3 for fMLP), whereas the incubation with GM-CSF produced no significant
      changes (89.1 +/- 4.8). When all the conditions were compared, the PMA effect was
      significantly higher than those observed with other stimuli; furthermore, the
      expression upon incubation with fMLP and LTB4 was statistically significant.
      These results suggest that the level of activation reached by granulocytes is
      directly related to their capacity for shedding L-selectin from the cell surface,
      and that these levels are lowered after the stimulation by chemotactic factors.
      GM-CSF activates several important functions of granulocyte cells, however it
      does not induce L-selectin shedding.

PMID- 11957367
TI  - [Mercury determination in prehispanic Colombian biological samples: first
      experiences and investigation perspectives].
AB  - Mercury is useful as a tracer of environmental pollution levels. We measured
      mercury levels in hair from two human mummies (XII and XIV centuries,
      respectively) and from a stag (Odocoileus virginianus). The total and inorganic
      mercury levels found in the samples were very low. This findings indicated a
      minimal exposure to mercury in food and its absence in the atmosphere. Mercury
      levels can be used to explore the relationship between humans and environment,
      especially after metallurgy appeared, and to assess environmental contamination
      in different periods.

PMID- 11957368
TI  - [Standardization of rabies virus genome amplification for its use in molecular
      epidemiology studies].
AB  - In order to improve the diagnosis and typification of rabies viruses at the
      Instituto Nacional de Salud National Reference Laboratory for rabies, we
      standardized techniques for the amplification of a 902 nucleotide DNA fragment,
      complementary to a selected region of the rabies virus genomic RNA. This region
      codes for a segment of both the glycoprotein and protein L, and contains the G-L
      intergenic noncoding region known as Pseudogen Psi. The standardized techniques
      included: 1) biological amplification of rabies viruses by intracerebral mouse
      inoculation; 2) total RNA extraction from the brains of infected mice, 3) RT-PCR
      amplification of a 902 nucleotide DNA fragment complementary to the selected RNA
      region. The study sample consisted of 30 rabies virus strains isolated from dogs
      and selected from the virus bank of the Virology Laboratory. Due to their
      simplicity the methods described have several advantages when compared to methods
      reported in previous papers. The technology proposed is a precise complement to
      rabies diagnosis techniques, and can be applied to the identification of
      phylogenetic relations among rabies isolates, and, therefore, it is also used to
      identify rabies transmission dynamics and geographical distribution.

PMID- 11957369
TI  - [The status of sexually transmitted diseases, Colombia, 1976-2000].

PMID- 11957370
TI  - Osteoarthrosis of the antebrachiocarpal joint of 7 riding horses.
AB  - Osteoarthrosis (OA) of the antebrachiocarpal joint from 7 riding horses is
      described. The horses were old mares and developed severe OA, with ankylosis in
      some of the joints. The lesions were bilateral, and the owners noticed the
      lameness in a late event. The cause of severe OA in these mares is not clear. The
      fact that OA was bilateral indicates that a single traumatic injury is unlikely
      as an etiologic factor. Considering the severe joint lesions it took long time
      before the horse-owners noticed the lameness. It is discussed if the threshold of
      pain is higher in the antebrachiocarpal joint compared with the middle carpal
      joint.

PMID- 11957371
TI  - Influence of ileo-caecal cannulation and oxytetracycline on ileo-caecal and
      rectal coliform populations in pigs.
AB  - The effect of surgery (insertion of an ileo-caecal cannula) and a subsequent
      parenteral treatment with oxytetracycline on the ileo-caecal and rectal coliform
      populations in 7 Swedish Yorkshire castrates were studied. Samples were collected
      during surgery as well as 3, 7, 14 and 20 days post surgery. The diversity of the
      enteric coliform flora was initially high both in the ileo-caecal ostium and in
      rectum. No alteration in the diversity of the enteric coliform flora was observed
      following surgery and treatment with oxytetracycline. As the insertion of ileo
      caecal cannulas did not affect the intestinal coliform flora this study gives
      support to the use of this technique to mirror processes in the small intestine
      of pigs. Further, the diversity of the enteric coliform flora was unaffected by
      the parenteral treatment with oxytetracycline.

PMID- 11957373
TI  - Persistence of Ehrlichia phagocytophila infection in two age groups of lambs.
AB  - Tick-borne fever (TBF) is caused by the rickettsiae Ehrlichia phagocytophila and
      is a common disease in sheep in tick (Ixodes ricinus) infested areas in Norway.
      Earlier investigations have shown that some sheep could remain infected for
      several months after the primary infection. In this study, the persistence of E.
      phagocytophila after experimental infection was investigated in 2 age groups of
      lambs. Six lambs (1-2 weeks old) and 14 lambs (6-8 months old) were inoculated
      intravenously with an ovine strain of E. phagocytophila and thereafter examined
      clinically (including daily body temperature recording) and by haematological and
      serological (E. equi antibodies) methods for the next 4 months. At the end of
      this period, the lambs were examined for a TBF infection by blood smear
      investigation and blood inoculation studies. The infection was demonstrated in 19
      (95%) of the 20 lambs.

PMID- 11957372
TI  - Predilection muscles and physical condition of raccoon dogs (Nyctereutes
      procyonoides) experimentally infected with Trichinella spiralis and Trichinella
      nativa.
AB  - The predilection muscles of Trichinella spiralis and T. nativa were studied in 2
      experimental groups of 6 raccoon dogs (Nyctereutes procyonoides), the third group
      serving as a control for clinical signs. The infection dose for both parasites
      was 1 larva/g body weight. After 12 weeks, the animals were euthanized and 13
      sampling sites were analysed by the digestion method. Larvae were found in all
      sampled skeleton muscles of the infected animals, but not in the specimens from
      the heart or intestinal musculature. Both parasite species reproduced equally
      well in the raccoon dog. The median density of infection in positive tissues was
      353 larvae per gram (lpg) with T. spiralis and 343 lpg with T. nativa. All the
      infected animals had the highest larvae numbers in the carpal flexors (M. flexor
      carpi ulnaris). Also tongue and eye muscles had high infection levels. There were
      no significant differences in the predilection sites between these 2 parasite
      species. Trichinellosis increased the relative amount of fat, but not the body
      weight in the captive raccoon dogs. Thus, Trichinella as a muscle parasite might
      have catabolic effect on these animals.

PMID- 11957374
TI  - Rapid brain cooling in intubated pigs through nasal flushing with oxygen:
      prevention of brain hyperthermia.
AB  - Local cooling of the brain by the respiratory air is found in many animal
      species. The mechanism is based on cooling of the nasal vein blood and heat
      transfer in the cavernous sinus/carotid artery complex and is therefore not
      active in anaesthetised, intubated animals. The present experiment was made to
      investigate the effects of oxygen flushing of the nasal cavities in such animals.
      Nine anaesthetised, intubated male pigs were used. The temperatures in the third
      ventricle and rectum were measured continuously. Oxygen was infused into the
      nasal cavities during 10 min periods interrupted by 10 min without flow. The
      nasal oxygen flow constantly induced a rapid, reversible and flow dependant
      decrease in brain temperature: 0.25 degree C +/- 0.04, (n = 2) (mean +/- SD, n)
      at < 4 l/min; 1.35 degrees C +/- 0.78, (n = 20) at 4-6 l/min; and 1.44 degrees C
      +/- 0.62, (n = 6) at > 6 l/min. The ventricle temperature decreased 0.59 degree C
      +/- 0.23, (n = 8) when the animals were transferred to spontaneous respiration
      and the tracheal tube removed. It may be possible to protect the brain in
      intubated animals and humans from heat-induced damages by establishment of nasal
      flushing.

PMID- 11957375
TI  - Housing, feeding and management of calves and replacement heifers in Swedish
      dairy herds.
AB  - A questionnaire was sent to 1500 randomly selected dairy herds in Sweden, asking
      for general information about the herds, including routines from birth to first
      calving and also routines at breeding, calving and during the grazing period.
      Fifty-eight percent of the questionnaires were returned. The preweaned calves
      were kept in individual calf pens in 68% and in group housing systems in 28% of
      the herds. Pens with slatted floors were the main housing system for replacement
      heifers from weaning to breeding, and tie stalls from breeding to first calving.
      Whole milk was used in 44% and milk replacements in 42% of the herds. The calves
      received, as a median, 2.5 litres of milk per meal and 2 meals per day. The
      median age at weaning was 8 weeks. Age was the single most common criteria used
      for deciding both weaning and breeding time. The median age when the heifers were
      first turned out to pasture was 6 months. Prophylactic anthelmintic treatment was
      used by 65% of the herds. The most common diet for replacement heifers before
      calving was a combination of grain, hay and silage.

PMID- 11957376
TI  - Investigations of waterborne pathogens in Eurasian beaver (Castor fiber) from
      Telemark County, southeast Norway.

PMID- 11957377
TI  - [Safety regarding invasive procedures in HIV-positive patients].
AB  - A 46-year-old man and a 58-year-old man, both known for several years with HIV
      infection, were admitted for operations due to aortic valve insufficiency (aortic
      valve replacement) and posttraumatic coxarthrosis (total hip replacement)
      respectively. In accordance with the protocol, preoperative viral infections
      (HIV, hepatitis B and C) were inventoried, the HIV viral load was lowered
      medicinally and the operation team informed. During each operation a consultant
      was present in the operating theatre to provide advice in the case of a
      needlestick or cut accident. No accidents occurred. Both patients were discharged
      to home in a good condition.

PMID- 11957378
TI  - [A new instrument to measure clinical outcomes].
AB  - De Haan et al. have developed a new disability score (Amsterdam linear disability
      score; ALDS) based on item response theory. The advantages of the instrument are
      its generic applicability for multiple disease categories of varying severity and
      its linear scaling as a continuous variable, which facilitates interpretation and
      requires smaller sample sizes. Moreover, such a tool may very well be used as
      complementary outcome measure in a subset of patients participating in a mega
      trial that concentrates on simple outcomes. A limitation is that users of the
      score still need to become familiar with its interpretation. It is not yet clear
      how many questions are needed to obtain a reliable estimate of the ALDS and
      therefore the time needed to complete the instrument is still uncertain.

PMID- 11957379
TI  - [Measuring the functional status of patients in clinical trials using modern
      clinimetric methods].
AB  - In clinical medicine numerous measurement instruments have been developed to
      assess the functional outcome of patients in clinical trials. The majority are
      questionnaires with multiple-choice items. The responses of the patients are used
      to calculate a sum score. However, there are some disadvantages associated with
      the use of sum scores. Modern clinimetric methods, based on item response theory
      (IRT) in combination with a calibrated item bank, can overcome these problems.
      When using this measurement technique, it is possible to arrange both the item
      difficulty and the patient's ability on a single, hierarchical linear scale. This
      allows the user to obtain a sufficiently detailed clinical picture using a small
      number of items. In addition to being efficient, this method makes it possible to
      present different sets of items to different groups of patients. Since all of the
      items are calibrated, the measurements remain comparable. The application of this
      innovative method of measuring is being studied in the ongoing 'Amsterdam linear
      disability score' (ALDS) project.

PMID- 11957380
TI  - [Screening for carriers of the fragile X syndrome; ethical exploration].
AB  - Large-scale population screening for carriers of fragile X syndrome is premature.
      Notably the limited possibilities to detect carriers (of an instable premutation)
      in the general population with certainty, poses some ethical dilemmas. The
      possible psychological consequences of this are unknown. A pilot study can only
      be started if the added value of population screening as opposed to cascade
      screening is plausible, and the requirement of proportionality is satisfied. If
      this is the case, preconceptional screening is preferable to prenatal screening.
      Information should be provided in a process-like manner as this fits in best with
      the decision-making process that possibly follows participation in a population
      screening for carriers of fragile X syndrome. Further research into the ethics of
      cascade screening is desirable. This screening can be carried out on a
      complementary basis to population screening.

PMID- 11957381
TI  - [Diagnostic image (82). A man with different leg colors. Onchocerciasis].
AB  - A 28-year-old male refugee from Sierra Leone complained about a darker colour of
      his left leg with slight itching. A subcutaneous nodule on the left leg was an
      onchocercoma. After treatment with ivermectin the itch disappeared and the
      difference in skin colour slowly subsided.

PMID- 11957382
TI  - [Reducing the risk of blood-transmitted infections of HIV, hepatitis B or C virus
      in a teaching hospital in Amsterdam--evaluation of a protocol for needlestick
      accidents among hospital staff during the period 1997-2001].
AB  - OBJECTIVE: To evaluate a protocol for hospital staff aimed at reducing their risk
      of exposure to blood-transmitted infections. DESIGN: Prospective. METHOD: In
      August 1997 a protocol was introduced to the Onze Lieve Vrouwe Gasthuis Hospital
      in Amsterdam, with procedures to be followed after percutaneous or mucocutaneous
      blood contact in which there was a chance of transmission of hepatitis B (HBV) or
      C (HCV), as well as guidelines for the prescription of post-exposure prophylaxis
      (PEP) after accidents with an HIV risk. In the period 1 August 1997-30 June 2001
      data were collected from registration forms that reported accidents and the
      ensuing events. RESULTS: A total of 403 accidents were reported by 138 (34.2%)
      physicians, 135 (33.5%) ward nurses, 46 (11.4%) operation assistants, 30 (7.4%)
      co-assistants, 21 (5.2%) analysts and 33 (8.2%) persons with another position.
      There was a constant increase in the number of reports over the period. The
      seroprevalence of the source patients was: 6.9% (25/360) HIV, 8.1% (6/74) HBV and
      6.3% (23/363) HCV. PEP was prescribed on 46 occasions: 15 times for an HIV
      positive source and 31 times for what was initially an unknown HIV source.
      Following the introduction of a rapid HIV test in September 1999, there was a
      reduction in the number of unnecessary PEP prescriptions from 4 in 1997, 7 in
      1998 and 16 in 1999 to 3 in 2000 and 1 in 2001. All 15 persons who were correctly
      started on a PEP treatment took the medication for a period of 28 days despite
      many side effects. No seroconversions were established during the follow-up
      period of 6 months.

PMID- 11957383
TI  - [Pancreas-preserving total duodenectomy due to familial adenomatous polyposis in
      4 patients].
AB  - In 4 patients with familial adenomatous polyposis (FAP) and multiple severe
      dysplastic adenomas in the duodenum (a 42-year-old woman and 3 men aged 44, 53
      and 33 years, respectively), pancreas-preserving total duodenectomy (PPTD) was
      carried out. In 2 of the patients, serious early post-operative complications
      arose (leakage and haemorrhage of the gastrojejunostomy, respectively), and 1
      patient developed a late complication (attacks of pancreatitis). During the 1-5
      year follow-up period, small villous adenomas were seen in the jejunum
      (neoduodenum) of 1 of the patients. PPTD is a technically possible procedure
      which allows targeted treatment to be carried out if duodenum polyps are found
      upon endoscopic examination.

PMID- 11957384
TI  - [Sensitisation to 'poffertjes' as a result of sleeping on a pillow containing
      buckwheat].
AB  - A 19-year-old man suffered an anaphylactic reaction after eating 'poffertjes'
      (small Dutch pancakes). This reaction appeared to be the result of an IgE
      mediated allergy to buckwheat, a principal ingredient of 'poffertjes'. It is
      highly likely that the patient was sensitised by sleeping on a pillow stuffed
      with buckwheat husk.

PMID- 11957385
TI  - [Post-exposure prophylaxis in Zambia; the experiences of a tropical disease
      specialist following a cut accidentally incurred while operating on an HIV
      positive patient].
AB  - The author, a 33-year-old man employed as a tropical diseases specialist in
      Zambia, accidentally cut himself during an operation on an HIV positive patient.
      After washing the wound, he took zidovudine and lamivudine and, on the advice of
      a counsellor and following logistical discussions with the Dutch Embassy,
      indinavir as well. Blood test results for HIV antibodies on the day of the
      accident, after 1 month and after 3 months were negative. After six months, two
      Zambian tests were positive and two Dutch tests negative. A confirmative test in
      the Netherlands using blood flown over from Zambia was negative for both anti-HIV
      and HIV RNA. For health professionals working abroad, there is a protocol for
      post-exposure prophylaxis. However, improvements to this can be made, for
      example, how and where diagnostic tests are carried out and where reliable HIV
      tests are carried out.

PMID- 11957386
TI  - [Post-exposure treatment against HIV outside of the hospital in Amsterdam,
      January-December 2000].
AB  - The Infectious Diseases Department of the Amsterdam Public Health Service
      regularly sees people who have possibly been exposed to human body fluids
      infected with hepatitis B virus (HBV), hepatitis C virus (HCV) or human
      immunodeficiency virus (HIV), as a result of incidents in either a non-hospital
      related occupation or during their leisure time. Until January 2000, people
      reporting possible exposure were referred to hospitals for HIV post-exposure
      prophylaxis (HIV-PEP), whereas for HBV and HCV, the tracing of the infection
      source and the follow-up took place at the Public Health Service clinic. Since
      the introduction of a new protocol in January 2000, the Public Health Service as
      well as a hospital can establish an indication for HIV-PEP and prescribe it. In
      2000, 322 persons reported to the Public Health Service. The source was tested in
      194 incidents and an HIV test was carried out on 104 occasions. In 19 cases HIV
      antibodies were found or the source was known to be HIV positive. A total of 50
      people were prescribed HIV-PEP; 16 times after a needle-stick accident, 22 times
      after a sexual accident, 6 times after a bite-wound and 6 times after direct
      exposure to human blood. The sources of 30 PEP recipients could be tested and
      after this 16 recipients could stop with the treatment due to a negative HIV
      test. In 4 cases PEP treatment was stopped following a review of the indication.
      Therefore, 30 people had an indication to complete the PEP treatment. Of these,
      more than 80% reported side effects and 3 people had to withdraw from the
      treatment at an early stage because of this. The implementation of the protocol
      has resulted in less confusion because the follow-up now takes place at one
      location. Compared to other studies, the average time between exposure and
      treatment is shorter and compliance is good. In the period up to 15 May 2001, no
      seroconversions had been observed.

PMID- 11957387
TI  - [Syphilis epidemic and an increase of the number of HIV infections among
      homosexual men attending the Amsterdam venereal disease clinic].
AB  - The registered number of cases of early infectious syphilis and of (ano)genital
      gonorrhoea among the attendees of the outpatient clinic for sexually transmitted
      diseases of the Amsterdam municipal health service shows a strong increase for
      both diagnoses in the period 1990-2001, notably in the last few years. Nearly all
      of this increase is accounted for by homosexual men. Syphilis increased mostly
      among men aged 35 years and over, gonorrhoea mostly among younger men. The
      population of older men also showed a distinct increase since 1997 in HIV
      incidence.

PMID- 11957388
TI  - Beyond the theoretical rhetoric: a proposal to study the consequences of drug
      legalization.
AB  - Drug legalization is a frequently-debated drug control policy alternative. It
      should come as little surprise, therefore, that the arguments in favor of both
      legalization and prohibition have resulted in a conceptual stalemate. While
      theoretical deliberations are unquestionably valuable, they seem to have
      propelled this particular issue to its limit. To date, no works have suggested
      any empirical studies that might test the framework and potential consequences of
      drug legalization. In the current study, the arguments surrounding the drug
      legalization debate are synthesized into a proposal for future research. Such a
      proposal illustrates that the core elements surrounding drug legalization are not
      only testable, but that the time may be right to consider such an empirical
      effort.

PMID- 11957390
TI  - The influence of spirituality on substance use of college students.
AB  - OBJECTIVES: The issue of substance use and the problems resulting from that use
      has become a major concern in the United States. The past decade has seen several
      new trends in substance use by college students and an increase in the effort to
      try and determine factors that may ameliorate the problem. Spirituality is one
      possible factor that may have some role in the phenomenon. Some research has been
      conducted on the relationship of spirituality to substance use but the results
      are mostly descriptive and concerned with religiosity rather than spirituality.
      The purpose of this study was to explore the relationship between a student's
      spiritual and religious beliefs and the impact of those beliefs on the decision
      to use substances. METHOD: A sample of 337 university students was surveyed using
      the CORE Alcohol and Drug Survey and several supplemental questions. RESULTS: In
      general, spirituality had a moderate buffering effect upon the decision to use
      alcohol and marijuana. This general protective effect exists for both alcohol use
      and binge drinking but dissipated as the students reached upper-class levels.
      CONCLUSION: Spirituality may play a significant role in the decision of college
      students to use substances. Further research should focus on this important
      factor. Also, implementation of spiritual aspects into university prevention and
      treatment programs may help boost efficacy rates.

PMID- 11957389
TI  - Substance use on school property among students attending alternative high
      schools in the United States.
AB  - We analyzed nationally representative data from the 1998 National Alternative
      High School Youth Risk Behavior Survey, conducted by the Centers for Disease
      Control and Prevention, to determine the prevalence of substance use on school
      property among alternative high school students in the United States, to describe
      the characteristics of students who use substances on school property, and to
      examine the interrelationships of substance-use behaviors. During the 30 days
      preceding the survey, nearly 48 percent of students used at least one substance
      on school property and 17 percent used more than one substance on school
      property. Males were more likely than females and white students were more likely
      than black or Hispanic students to have used substances on school property. The
      results of this and other studies suggest that school administrators, public
      health practitioners, and policy makers should work to improve strategies for
      reducing substance use in this heterogeneous, hard-to-reach population.

PMID- 11957391
TI  - Evaluating the effectiveness of student assistance programs in Pennsylvania.
AB  - This article presents data from an evaluation of the Pennsylvania Student
      Assistance Program (SAP). Focusing on both program process and effectiveness, the
      evaluation was conducted to determine the overall efficacy of SAPs in
      Pennsylvania and, more specifically, how SAP is currently being implemented. Five
      data collection strategies were employed: statewide surveys of SAP team members
      and county administrators, focus groups, site visits, and the Pennsylvania
      Department of Education SAP Database. A total of 1204 individual team members
      from 154 school buildings completed the team member survey. Fifty-three county
      administrators completed the county administrator survey. Focus groups were
      comprised of SAP coordinators, school board personnel and community agency staff.
      Site visits were conducted at five schools. The findings of the evaluation
      indicate that SAP in Pennsylvania is being implemented as designed. Recommended
      is the development of benchmarks and indicators that focus on the best SAP
      practices and the extent to which various indicators of the effectiveness of SAP
      are occurring at appropriate levels.

PMID- 11957392
TI  - Moral reasoning and consistency of belief and behavior: decisions about substance
      abuse.
AB  - In view of implications of Kohlberg's theory of moral development, two hypotheses
      were considered in two independent studies: a) individuals who consider the use
      of potentially harmful substances to be morally wrong will be less likely to use
      such substances than peers who view such activities as a personal choice; and b)
      compared to those who are less mature, more mature moral reasoners display more
      consistency between their expressed beliefs about the morality of drug use and
      their reports of actual drug use. Two samples of college students, 29 men and 59
      women in Study 1 and 46 men and 100 women in Study 2, served as participants. All
      completed questionnaires about their use of tobacco, alcohol, and illicit drugs
      and their beliefs about the morality of using these substances. Participants in
      Study 2 also responded to the Defining Issues Test (DIT) to assess their level of
      moral thinking. Results from Study 1 supported hypothesis (a). Findings from
      Study 2 supported hypotheses (a) and (b).

PMID- 11957393
TI  - Evaluation of the All Stars Program: student and teacher factors that influence
      mediators of substance use.
AB  - The authors examined the relationship between students' perceptions of a problem
      behavior prevention program, All Stars, and changes in the program variables.
      Three factors--Program Enjoyment, Student Engagement, and Teacher Relationship-
      were used to predict changes in the four variables targeted by the All Stars
      program. Student Engagement was related to greater changes in student idealism,
      commitment, and bonding. Program Enjoyment was related to positive changes in
      student idealism and normative beliefs. Teacher Relationship had little impact on
      the program variables. Students who were taught All Stars by regular classroom
      teachers reported greater Program Enjoyment and Student Engagement than students
      taught by health education specialists.

PMID- 11957394
TI  - Evaluation of a tobacco prevention program on knowledge, attitudes, intention and
      behavior of tobacco use among fourth grade students--a preliminary study.
AB  - This was a preliminary study to evaluate the effectiveness of a tobacco
      prevention program on knowledge, attitude, intention, and behavior of tobacco use
      among fourth-grade students in four north central Florida counties. The results
      suggest that the program was effective in improving students' knowledge,
      attitudes, and intention toward not using tobacco products. Data analysis showed
      that students in the education group had a greater improvement in knowledge than
      the comparison group. Students in the education group also improved their
      attitude and intention scores while the comparison group did not show any
      improvement. The results also indicated positive responses from the students. In
      addition, teachers also gave a very positive response to the program.

PMID- 11957395
TI  - Fish cognition: a primate's eye view.
AB  - We provide selected examples from the fish literature of phenomena found in fish
      that are currently being examined in discussions of cognitive abilities and
      evolution of neocortex size in primates. In the context of social intelligence,
      we looked at living in individualized groups and corresponding social strategies,
      social learning and tradition, and co-operative hunting. Regarding environmental
      intelligence, we searched for examples concerning special foraging skills, tool
      use, cognitive maps, memory, anti-predator behaviour, and the manipulation of the
      environment. Most phenomena of interest for primatologists are found in fish as
      well. We therefore conclude that more detailed studies on decision rules and
      mechanisms are necessary to test for differences between the cognitive abilities
      of primates and other taxa. Cognitive research can benefit from future fish
      studies in three ways: first, as fish are highly variable in their ecology, they
      can be used to determine the specific ecological factors that select for the
      evolution of specific cognitive abilities. Second, for the same reason they can
      be used to investigate the link between cognitive abilities and the enlargement
      of specific brain areas. Third, decision rules used by fish could be used as
      'null-hypotheses' for primatologists looking at how monkeys might make their
      decisions. Finally, we propose a variety of fish species that we think are most
      promising as study objects.

PMID- 11957396
TI  - A fish-eye lens for comparative studies: broadening the scope of animal
      cognition.

PMID- 11957397
TI  - On the usefulness and limits of functional analogies.

PMID- 11957398
TI  - Do tufted capuchin monkeys (Cebus apella) spontaneously deceive opponents? A
      preliminary analysis of an experimental food-competition contest between monkeys.
AB  - A new laboratory procedure which allows the study of deceptive behavior in
      nonhuman primates is described. Pairs of tufted capuchin monkeys faced each other
      in a food-competition contest. Two feeder boxes were placed between the monkeys.
      A piece of food was placed in one of the boxes. The subordinate individual was
      able to see the food and to open the box to obtain the bait. A dominant male was
      unable to see the food or to open the box but was able to take the food once the
      box was opened by the subordinate. In experiment 1, two of four subordinate
      monkeys spontaneously started to open the unbaited box first with increasing
      frequency. Experiment 2 confirmed that this "deceptive" act was not due to a drop
      in the rate of reinforcement caused by the usurping dominant male, under the
      situation in which food sometimes automatically dropped from the opened box. In
      experiment 3, two subordinate monkeys were rerun in the same situation as
      experiment 1. One of them showed some recovery of the "deceptive" act but the
      other did not; instead the latter tended to position himself on the side where
      there was no food before he started to open the box. Although the results do not
      clearly indicate spontaneous deception, we suggest that operationally defined
      spontaneous deceptive behaviors in monkeys can be analyzed with experimental
      procedures such as those used here.

PMID- 11957400
TI  - Generalisation: mechanistic and functional explanations.
AB  - An overview of mechanistic and functional accounts of stimulus generalisation is
      given. Mechanistic accounts rely on the process of spreading activation across
      units representing stimuli. Different models implement the spread in different
      ways, ranging from diffusion to connectionist networks. A functional account
      proposed by Shepard analyses the probabilistic structure of the world for
      invariants. A universal law based on one such invariant claims that under a
      suitable scaling of the stimulus dimension, generalisation gradients should be
      approximately exponential in shape. Data from both vertebrates and invertebrates
      so far uphold Shepard's law. Some data on spatial generalisation in honeybees are
      presented to illustrate how Shepard's law can be used to determine the metric for
      combining discrepancies in different stimulus dimensions. The phenomenon of peak
      shift is discussed. Comments on mechanistic and functional approaches to
      generalisation are given.

PMID- 11957399
TI  - Matching visual stimuli on the basis of global and local features by chimpanzees
      (Pan troglodytes) and rhesus monkeys (Macaca mulatta).
AB  - This study was designed to examine whether chimpanzees and monkeys exhibit a
      global-to-local precedence in the processing of hierarchically organized compound
      stimuli, as has been reported for humans. Subjects were tested using a sequential
      matching-to-sample paradigm using stimuli that differed on the basis of their
      global configuration or local elements, or on both perceptual attributes.
      Although both species were able to discriminate stimuli on the basis of their
      global configuration or local elements, the chimpanzees exhibited a global-to
      local processing strategy, whereas the rhesus monkeys exhibited a local-to-global
      processing strategy. The results suggest that perceptual and attentional
      mechanisms underlying information-processing strategies may account for
      differences in learning by primates.

PMID- 11957401
TI  - Understanding of the relationship between seeing and knowing by tufted capuchin
      monkeys (Cebus apella).
AB  - The ability of four tufted capuchin monkeys (Cebus apella) to recognize the
      causal connection between seeing and knowing was investigated. The subjects were
      trained to follow a suggestion about the location of hidden food provided by a
      trainer who knew where the food was (the knower) in preference to a trainer who
      did not (the guesser). The experimenter baited one of three opaque containers
      behind a cardboard screen so that the subjects could not see which of the
      containers hid the reward. In experiment 1, the knower appeared first in front of
      the apparatus and looked into each container; next, the guesser appeared but did
      not look into any containers. Then the knower touched the correct cup while the
      guesser touched one of the three randomly. The capuchin monkeys gradually learned
      to reach toward the cup that the knower suggested. In experiment 2, the subjects
      adapted to a novel variant of the task, in which the guesser touched but did not
      look into any of the containers. In experiment 3, the monkeys adapted again when
      the knower and the guesser appeared in a random order. These results suggest that
      capuchin monkeys can learn to recognize the relationship between seeing and
      knowing.

PMID- 11957402
TI  - The generalization of deferred imitation in enculturated chimpanzees (Pan
      troglodytes).
AB  - Deferred imitation of object-related actions and generalization of imitation to
      similar but not identical tasks was assessed in three human-reared (enculturated)
      chimpanzees, ranging in age from 5 to 9 years. Each ape displayed high levels of
      deferred imitation and only slightly lower levels of generalization of imitation.
      The youngest two chimpanzees were more apt to generalize the model's actions when
      they had displayed portions of the target behaviors at baseline, consistent with
      the idea that learning is more likely to occur when working within the "zone of
      proximal development." We argue that generalization of imitation is the best
      evidence to date of imitative learning in chimpanzees.

PMID- 11957403
TI  - Malpractice insurance rates reach boiling point. Physicians burned by lawyers,
      lawsuits and jury awards.
AB  - Costs of medical malpractice insurance are soaring. Major insurers are refusing
      to write policies. And doctors are struggling to pay their premiums. Find out
      what's behind the insurance crisis.

PMID- 11957404
TI  - 10 ways to reduce medical malpractice exposure.
AB  - Communicating with patients, keeping accurate records and actually taking time to
      examine patients are three of the top 10 ways to avoid a lawsuit. Find out more
      in this article by a doctor who's reviewed over 200 malpractice cases.

PMID- 11957405
TI  - Doctors, lawyers evaluate each other in new study.
AB  - Asking doctors and lawyers what they like and dislike about each other brings
      strong, often negative results. Take a look at the level of trust between doctors
      and lawyers and learn how both sides view one another. And discover ways to patch
      up the rocky relationships.

PMID- 11957406
TI  - Coping with bad news: the physician executive's role in a lawsuit.
AB  - In these days of doctors, lawyers and lawsuits, chances of an American physician
      finishing his or her career without a malpractice claim are growing more remote.
      Every physician executive overseeing the activities of a group of peers knows
      this and should be prepared to assist the physician who is sued. Examine four key
      ways to help your physicians deal with the stress of a lawsuit.

PMID- 11957407
TI  - Who supports physicians in malpractice cases?
AB  - Malpractice suits have a devastating emotional impact on physicians. Learn about
      a unique service offered by the HealthTexas Provider Network to help doctors deal
      with the shock and sadness.

PMID- 11957408
TI  - Clinical practice guidelines and medical malpractice.
AB  - As clinical practice guidelines become more and more prevalent, they will define
      the requisite "standard of care" for medical treatment and impact medical
      malpractice litigation. They may even replace expert testimony.

PMID- 11957409
TI  - American Indian health care at core of Wyllie's world.

PMID- 11957410
TI  - Preventing civil war. A case study for physician CEOs.

PMID- 11957411
TI  - Building trust and collaboration between physicians and administrators.
AB  - If you think someone else's behavior is blocking you from achieving a goal, think
      again. As a physician leader, there may be something you can do to take
      responsibility for a situation and make the necessary changes. Learn how you can
      help build the trust and cooperation needed to make change happen.

PMID- 11957412
TI  - Physician practice management companies: a failed concept.
AB  - Is there a lesson? Famed investor Warren Buffet claims he never buys a company
      unless he personally understands the business. He admits he has missed a few real
      opportunities in the high technology sector. However, he is pleased to have
      avoided many disasters. Many physicians entered into PPMC deals without
      completely understanding the concept. Perhaps the lesson is to simply avoid a
      deal that does not make sense. Understand the market. Understand the business. If
      you, as a buyer, seller or partner cannot clearly understand how a transaction
      creates value that you can capture, walk away.

PMID- 11957413
TI  - Determining physician compensation--Part I.

PMID- 11957414
TI  - Waves or particles?

PMID- 11957415
TI  - How to use outside collection agencies. Don't simply charge off accounts and
      forget them.
AB  - Collection agencies may be the key to receiving payment on overdue bills. Learn
      how they work and what to look for in a reputable collection agency.

PMID- 11957416
TI  - Valuing and comparing physician benefits.

PMID- 11957417
TI  - Focus, exchange and trust mark successful entrepreneurs.

PMID- 11957418
TI  - VPMA = very busy day. Physician executive faces many meetings, critical decisions
      in typical day. Interview by Barbara J. Linney.

PMID- 11957419
TI  - Strong career plan helps turn dreams into reality.

PMID- 11957420
TI  - Managing terror. Public health officials learn lessons from bioterrorism attacks.
AB  - When a photo-journalist presented with the first case of inhalation anthrax in
      the United States in 23 years, it marked the worse case of biological terrorism
      in our nation's history. It also marked a significant management challenge for
      numerous local, state and federal officials. Review what was learned and how we
      can better prepare for future attacks.

PMID- 11957421
TI  - Progress towards the global eradication of poliomyelitis, 2001.

PMID- 11957422
TI  - [Drugs to pregnant and breast feeding women].

PMID- 11957423
TI  - [Should normotensive diabetic patients with microalbuminuria be treated with
      angiotensin converting enzyme inhibitors?].

PMID- 11957424
TI  - [Training of back and neck in the year of 2002].
AB  - The aim of this review was to determine the relevance of exercise therapy in the
      total treatment strategy of low back pain (LBP). The review is based on the
      results of randomised clinical trials, meta-analysis, consensus reports, and
      medical technology assessments. There is strong evidence for the effectiveness of
      exercise therapy for subacute and chronic LBP. There is some evidence that
      exercise is not effective for acute LBP. The most effective exercise programme
      and the optimal combination of exercise and other effective treatment modalities
      for different subgroups of LBP patients remain to be determined. Insights
      regarding the biological mechanisms of the positive effect of exercise are not
      yet established.

PMID- 11957425
TI  - [Breast feeding and treatment with antidepressive agents. A literature review].
AB  - Depression after delivery occurs frequently and, apart from being very painful,
      it may cause disturbance in the child's development. A number of these
      depressions are so severe that medical antidepressant treatment is indicated.
      This raises the question whether this kind of treatment should call for
      interruption of breast-feeding. The problem is, however, that breast-feeding is
      of major importance to the child, as well as to the mother. A review of present
      knowledge about the excretion of antidepressants in breast milk and the reports
      on the possible effects on the child would be useful, in order to create a
      qualified basis for decision-making, together with the patient, on whether or not
      to interrupt the breast-feeding. Furthermore, examination of the references would
      result in concrete guidelines for the most appropriate way of dealing with the
      treatment, if it is decided to continue the breast-feeding.

PMID- 11957426
TI  - [Increased frequency of driving accidents in epilepsy].
AB  - INTRODUCTION: The influence of medical conditions on the ability to drive safely
      is a matter of concern to both physicians and society. Satisfactory answers to
      the many questions are not yet available, because of methodological difficulties,
      including the inability to collect sufficiently large and representative samples
      of drivers with specific diseases, and to acquire reliable accident data. For
      epilepsy, the conclusions of scientific reports vary from "there is little to
      worry about" to an increased relative risk of 1.9. As a consequence, attitudes
      and regulations vary greatly throughout the world. MATERIAL AND METHODS: A ten
      year historical cohort register study of 159 patients with epilepsy and 559
      controls individually matched for age, gender, place of residence, and exposure
      period. Recorded diagnoses of other relevant diseases led to exclusion. The
      outcome measure was treatment at the casualty department after an accident as a
      car driver. RESULTS: Ten patients and five controls had been treated at the
      casualty department, the rate ratio per 1,000 person-years with exposure being
      7.01 (CI 2.18-26.13). DISCUSSION: This study showed that drivers with epilepsy
      seven times more often than healthy controls were treated at a casualty
      department after having a road traffic accident. In view of the small numbers of
      accidents and the surprising findings, the results must be interpreted
      cautiously. It is not advisable at this time to liberalize demands, but, on the
      other hand, drastic inferences regarding the patients' automobile driving should
      be avoided until the results have been further substantiated.

PMID- 11957427
TI  - [Correlation between the prevalence of schizophrenia and the sociodemographic
      status in different areas of Copenhagen].
AB  - INTRODUCTION: The results of a statistical study of the prevalence of
      schizophrenia are presented. The study was designed to determine whether the
      prevalence of schizophrenic patients admitted to Copenhagen Community Hospital
      (KH) in 1994 was higher in the low sociodemographic areas of Copenhagen and lower
      in the high sociodemographic areas. The Jarman's underprivileged area score (UPA
      score) was used as the sociodemographic index. MATERIAL AND METHODS: The study
      was a retrospective case-referent study. One hundred and eighty-seven patients
      admitted to KH on the diagnosis of schizophrenia and who were living in one of
      the four communities connected to KH comprised the study group. RESULTS: A high
      correlation was found between the prevalence of schizophrenia and the UPA score
      in the four communities (r = 0.87), but the result was not significant (t:p =
      0.15). DISCUSSION: The high correlation shows that there is a tendency for
      schizophrenic people to live in the low sociodemographic areas of Copenhagen, but
      the statistical material is too small to rule out the possibility that this is a
      statistical fluctuation. To show a statistically significant correlation, a
      larger study is needed.

PMID- 11957429
TI  - [Localized lipohypertrophy during growth hormone therapy].
AB  - Accumulation of subcutaneous fat is described in a 51-year-old woman with
      panhypopituitarism treated on all insufficient pituitary axes, including growth
      hormone (GH). Malnutrition and alcoholic liver disease caused reduced synthesis
      of hepatic insulin-like growth factor I (IGF-I), and the function of IGF-I as
      biochemical marker of the GH effect was compromised. Peripheral levels of GH and
      IGF-I in tissues may have reached supra physiological levels and induced
      localised lipohypertrophy. Adjustment of GH treatment should not rest in all
      cases on IGF-I alone, but also depend on the clinical effect. Adjustment should
      follow suspected adverse events, such as lipohypertrophy, which is, however, an
      unusual complication of GH therapy.

PMID- 11957428
TI  - [Can we rely on the results of urine microscopy and culture when tests are
      performed in general practice?].
AB  - INTRODUCTION: Urinary tract infections (UTI) account for 2-5% of consultations in
      general practice, but only about half the patients with dysuria have significant
      bacteriuria (> 100,000 bacteria per ml). A microbiological diagnosis can be made
      by examination of a urine sample, and in Danish family practice the diagnosis of
      UTI is often reached by a microscopic analysis or a dip-slide culture test. These
      methods have a high validity when performed in hospital, but we need knowledge
      about the validity of microbiological urine examinations when performed in
      general practice. The aim of this study was to validate detection of bacteriuria
      by urine microscopy and dip-slide culture in general practice. MATERIAL AND
      METHODS: Urine specimens artificially produced by adding a known quantity of
      bacteria (Escherichia coli, Proteus mirabilis, Enterobacter cloacae,
      Staphylococcus epidermidis and Enterococcus faecalis) to sterile urine were sent
      to 25 general practices for microscopic examination and dip-slide culture. No
      prior instruction in testing procedure was given. As the gold standard, the
      results of a standardised culture method performed by skilled laboratory
      technicians at the Department of Microbiology, University of Southern Denmark,
      were used. RESULTS: Significant bacteriuria was identified by microscopy with a
      sensitivity of 95% and a specificity of 83%. The corresponding figures for urine
      culture were 95% and 96%. The morphology of bacteria was interpreted correctly in
      80% of microscopic examinations, and 60% of the bacteria strains were classified
      correctly in terms of their motility. DISCUSSION: The results of urine microscopy
      and culture performed in general practice are to be relied on.

PMID- 11957430
TI  - [Epicrises up to date!].

PMID- 11957431
TI  - [New actors in type 2 diabetes].

PMID- 11957432
TI  - [Otitis media and antibiotics].

PMID- 11957433
TI  - [The CARMEN study].

PMID- 11957434
TI  - [Pain].

PMID- 11957435
TI  - [Gene therapy and cancer].

PMID- 11957436
TI  - [Clinical use of pain measurement techniques].
AB  - The increased knowledge about pain has lead to the suggestion of a mechanism
      based classification of pain, and hence mechanism-based therapy. The
      implementation of this classification is unlikely to occur in the near future,
      but the concept as such emphasises the importance of a better understanding of
      the origin of pain before treatment is initiated. The basis for developing and
      applying such an approach in the future is accessibility to pain assessment
      techniques, which are able to measure and quantify patients' responses to pain.
      Experimental clinical research includes a number of techniques to assess the
      excitability of the pain system and the manifestations related to central
      sensitisation and neuroplasticity. This can now be applied for mechanism-based
      diagnosis and related targeted treatment. As the new generation analgesics with
      new sites of action are developed, a mechanisms-based approach could, it is
      hoped, lead to more rational management of pain in the future.

PMID- 11957437
TI  - [New knowledge about the mechanisms of pain].
AB  - Over the last 10-15 years, scientific knowledge related to the neurobiology of
      pain systems has expanded substantially. Today the pain system cannot be regarded
      as static, but one that can undergo substantial neuroplastic changes. These can
      be increased effectiveness of synaptic transmission, up and/or down regulation of
      peptides in the dorsal root ganglion, increased and/or decreased expression of
      receptors. The manifestations of such changes can be pain evoked by normally non
      painful stimuli (allodynia) or a heightened reaction to painful stimuli
      (hyperalgesia). Such reactions are seen in neuropathic pain conditions and are
      difficult to treat with conventional therapies. In the near future, greater
      knowledge of the neurobiology of pain may lead to new and more specific
      analgesics.

PMID- 11957438
TI  - [Extrapulmonary complications of Mycoplasma pneumoniae infections].
AB  - INTRODUCTION: Mycoplasma pneumoniae is a common cause of atypical pneumonia in
      children and young adults. The infection is generally mild and only a very few
      patients are admitted to hospital. However, extrapulmonary complications are well
      recognised--mostly as manifestations from the central nervous system (CNS).
      MATERIAL AND METHODS: We describe 21 patients with M. pneumoniae infection seen
      at Rigshospitalet, Copenhagen, from 1994 to 2000. RESULTS: The patients had
      fever, headache, myalgia, and cough. Biochemically, they were characterised by
      leucocytosis, an increased level of C-reactive protein, and infiltrations on the
      chest x-ray. A total of seven patients developed extrapulmonary complications to
      the infection in the form of encephalitis (3), polyradiculitis (1), transversel
      myelitis (1), erythema multiforme (3), cardial arrhythmia (1), and haemolytic
      anaemia (2). Three patients had more than one complication at the same time.
      DISCUSSION: The incidence of patients with complications to M. pneumoniae
      infection was higher than that reported in the literature, probably because these
      patients are typically submitted to the Department of Infectious Diseases,
      Rigshospitalet. The pathogenesis of extrapulmonary complications to M. pneumoniae
      infection is unknown.

PMID- 11957439
TI  - [Thoracoscopic lobectomy. The first experiences in Denmark].
AB  - INTRODUCTION: This article reports the introduction of VATS (video-assisted
      thoracic surgery) lobectomy in lung cancer patients in our department. METHODS:
      From 22 October 1999 to 15 December 2000, ten patients with peripheral primary
      lung cancer with no signs of spreading underwent VATS lobectomy. In an additional
      four patients, the resection started as VATS, but had to be converted to an open
      procedure. RESULTS: No 30 day mortality or late complications were seen. One
      patient who developed empyema underwent surgery and one had a stroke, but with
      total remission. DISCUSSION: We have shown that it is possible to introduce VATS
      lobectomy with acceptable results. A literature overview demonstrates that
      thoracoscopic lobectomies offer similar survival data to that of conventional
      surgery.

PMID- 11957440
TI  - [One-year effect of health counseling on life style and risk factors of heart
      disease].
AB  - INTRODUCTION: We examined the need for counselling and the effect on willingness
      and ability to change life-style, and subsequent changes in risk factors for CHD.
      MATERIAL AND METHODS: All 152 male employees in a computer company, 25-45 years
      of age, were invited to participate in a controlled intervention study over one
      year. The subjects were randomised to an intervention group (I group) and a
      control group. The I group was divided into subgroups based on baseline behaviour
      and risk factor status. Changes were evaluated after one year. After an initial
      health examination, participants in the I group were counselled at baseline and
      at 5 months. RESULTS: Eighty-five (56%) men participated. Twenty-nine were
      assigned to a control group and 56 to an intervention group (I group) (dropouts =
      8). An exercise group (E group) was advised to take up aerobics exercise three
      times/week, a diet group to reduce the intake of saturated fat and increase fish
      products, and smokers to stop smoking. Forty were recommended one or more
      behavioural changes and eight had no need. Thirty-four were willing to make
      behavioural changes. Compared to the control group, the fitness level increased
      (p < 0.01) and body weight decreased in the I group (p < 0.05). DISCUSSION:
      Individual counselling promotes regular exercise with subsequent improvements in
      CHD risk factors. The diet and smoking counselling models were less successful in
      terms of compliance.

PMID- 11957442
TI  - [Vaginal stenosis: a possible finding in Behcet's syndrome].
AB  - A 27-year-old Kosovo-Albanian woman with recurrent oral and genital ulcerations,
      arthralgias, erythema nodosum, and eye symptoms, was admitted for dyspareunia.
      Objective findings met the diagnostic criteria for Behcet's syndrome (BS). An
      unexpected narrow fibrotic ring was found in the vagina. Two incisions were made
      and the diameter was normalised. She was treated with prednisolone and Imuran,
      with good symptom relief. BS might be a differential diagnostic hint when
      inexplicable vaginal stenosis occurs.

PMID- 11957441
TI  - [Beta-thalassemia in a Danish family].
AB  - We report a case of beta-thalassaemia in a family of Danish origin, owing to a C
      to T substitution in codon 39 of the beta-globin gene.

PMID- 11957443
TI  - [Guidelines on breaking bad news. A quality assurance work at own department].

PMID- 11957444
TI  - [Picture of the month: Behcet's syndrome].

PMID- 11957445
TI  - [Ventilation/perfusion lung scintigraphy in pulmonary embolism].

PMID- 11957446
TI  - [The big nutrition campaigns are effective].

PMID- 11957447
TI  - [Human papillomavirus testing. Important to differ between screening and
      diagnostics].

PMID- 11957448
TI  - Exploring frameless stereotactic image guided surgery.
AB  - Frameless stereotactic image guided surgery (IGS)--a fairly new modality
      originally used in cranial neurosurgical procedures--has been found to have
      several advantages over traditional framed methods of three-dimensional
      navigation. Frameless stereotactic IGS is proving useful in neurosurgical
      procedures by allowing screws to be placed in the spine more quickly and
      accurately than with traditional methods. As IGS becomes standard clinical
      practice for certain spinal procedures--overlapping both neurosurgery and
      orthopedic specialties--new ideas for surgical application of the technology are
      developing. Currently, frameless stereotactic IGS is being investigated for use
      in hardware placement in orthopedic procedures and for endoscopic navigation in
      otorhinolaryngologic sinus procedures. Frameless stereotactic IGS is expected to
      gain application approval in both orthopedic and otorhinolaryngologic specialties
      from the US Food and Drug Administration in the near future.

PMID- 11957449
TI  - Use of decompressive craniectomy after severe head trauma.
AB  - Ten percent of head injuries quality as "severe," requiring prompt diagnosis and
      treatment. This level I trauma center uses an aggressive approach to treatment of
      severe head injuries and, when indicated, intervenes with decompressive
      craniectomy. This article explains decompressive craniectomy, including
      indications, procedures, and protocols. The case studies presented highlight two
      patients with profound head injuries. Additionally, cranioplasty replacement of
      autograft flap is explained and discussed.

PMID- 11957450
TI  - Temporary abdominal closure using an i.v. bag silo for severe trauma.
AB  - Patients with severe abdominal trauma injuries can have improved outcomes if a
      priority-oriented approach is taken to surgical intervention. This includes
      temporary abdominal closure and planned reoperation to complete complex, lengthy
      procedures when the patient is stabilized. Temporary abdominal closure can be
      achieved safely and cost-effectively by using a presterilized 3-liter cystoscopy
      fluid i.v. bag. This article discusses the rationale for temporary abdominal
      closure and planned reoperation, physiologic considerations in abdominal
      compartment syndrome (ACS), abdominal injuries or conditions leading to ACS, and
      manifestations of ACS. It compares and contrasts various materials used for
      temporary abdominal closure, illustrates bag preparation and silo application and
      removal, and analyzes complex intraoperative and postoperative nursing
      activities.

PMID- 11957451
TI  - The millennium bug--do we have the right antibiotics?
AB  - This article introduces readers to the scope of the Year 2000 (Y2K) issue. In
      addition to describing how this problem came to be, the author examines the
      extent of the problem as defined by professionals in information technology. The
      author also explores what the cost of fixing the problem may be and what industry
      is doing to mitigate the effects the Y2K bug will have on patient care, supplies,
      and financial operations. The author expresses the need for caregivers to have a
      greater interest in the problem and to ask questions about what is being done at
      individual institutions.

PMID- 11957452
TI  - A systems approach to resolving OR conflict.
AB  - Effective communication and courteous interaction with other hospital departments
      are essential for a smooth-running OR. To function effectively in a perioperative
      setting, OR personnel need patience, knowledge, and skill in problem-solving
      techniques. When health care employees are not taught these techniques and
      protocols are not in place to manage conflict, friction develops and productivity
      suffers. In this article, conflict situations between two hospital departments
      and on OR are presented to characterize successful conflict resolution methods
      using a systems approach. The results include reduction of surgical procedure
      delays, efficient ordering of supplies, and improved interpersonal relations.

PMID- 11957453
TI  - Laparoscopic splenectomy in children with sickle cell disease.
AB  - Sickle cell disease is a group of genetic disorders that are characterized by the
      production of hemoglobin S, anemia, and acute and chronic tissue damage secondary
      to blockages caused by abnormally shaped (i.e., sickle-shaped) red blood cells.
      In children, complications of sickle cell disease (e.g., splenic sequestration
      and splenomegaly) increase the risks for postoperative complications due to the
      physical stress of the large incisions previously require for splenectomy. An
      intracorporeal splenic fragmentation technique is now being used to avoid these
      complications and will be discussed in this article.

PMID- 11957454
TI  - Recommended practices for high-level disinfection. Association of Operating Room
      Nurses.

PMID- 11957455
TI  - Recommended practices for surgical tissue banking. Association of Operating Room
      Nurses.

PMID- 11957456
TI  - Polypharmacy and elderly patients.
AB  - Medication therapy in elderly patients is difficult to manage and always has the
      potential of being hazardous. With the age-related changes that affect the
      pharmacokinetics and pharmacodynamics of a medication, prescribing medications is
      further complicated. Similarly, assessment of a medication's efficacy is
      difficult. The situation becomes more complicated when the patient is taking
      multiple medications. Nurses in the perioperative area need to be cognizant of a
      patient's preoperative medication regime and the medications that have been
      prescribed in the perioperative setting. As medication interactions increase
      substantially with the number of medications taken, the most pertinent nursing
      intervention is accurate assessment of the patient. Early recognition of
      potentially harmful medication effects is critical.

PMID- 11957457
TI  - A practical tip to eliminate the anesthesia screen.

PMID- 11957458
TI  - Investing in the future--an OR orientation program for nursing students.

PMID- 11957459
TI  - Legislative activity on the Interstate Compact for the Mutual Recognition Model
      on Nursing Regulation.

PMID- 11957460
TI  - Sickle cell resources online; browsing the Internet.

PMID- 11957461
TI  - Nursing and Midwifery Council. Clocking in at the council.

PMID- 11957462
TI  - Would sharing power with nurses improve GPs' working conditions?

PMID- 11957463
TI  - Facts and fantasy.

PMID- 11957464
TI  - Fudge of ages.

PMID- 11957465
TI  - High time for drugs.

PMID- 11957466
TI  - Close encounters of the sexual kind.

PMID- 11957467
TI  - Are nurses fit for clinical benchmarking?

PMID- 11957468
TI  - Technical excellence doesn't make a nurse, TLC does.

PMID- 11957469
TI  - The secret of telling patients the truth.

PMID- 11957470
TI  - Nursing and the perfect bun.

PMID- 11957471
TI  - Personal connection is nursing's foundation--even on the phone.

PMID- 11957472
TI  - It's the thought that counts.

PMID- 11957473
TI  - Curtains to shoddy, second-rate care.

PMID- 11957474
TI  - Helping one mother's son to go on with his life.

PMID- 11957475
TI  - The talent to challenge received wisdom.

PMID- 11957476
TI  - Breastfeeding. Are we just bottling out?

PMID- 11957477
TI  - Wider prescribing powers are welcome but there are crucial lessons from the
      pilots.

PMID- 11957478
TI  - Sisters doing it for themselves.

PMID- 11957479
TI  - Central venous catheters: some common clinical questions.

PMID- 11957480
TI  - A new way to link research.

PMID- 11957481
TI  - Preventing unwanted teenage pregnancies.

PMID- 11957482
TI  - Nurse prescribing. Frustration at limit of reform.

PMID- 11957483
TI  - Recruitment. DoH says it has 'turned tanker around'.

PMID- 11957484
TI  - Nurse-led discharge planning improves quality of care.

PMID- 11957485
TI  - Beds mattresses and cushions for pressure sore prevention and treatment.

PMID- 11957486
TI  - Stoma care--5(a). Problem-solving.

PMID- 11957487
TI  - Fit for practice. 5.2: Legal issues in accountability.

PMID- 11957488
TI  - Women should accept natural labour pains.

PMID- 11957489
TI  - Violence against staff. Minister steps into row over controversial assessments.

PMID- 11957490
TI  - NHS facing massive bills.

PMID- 11957491
TI  - Patient consent. Hidden benefits.

PMID- 11957492
TI  - Sudden infant death syndrome. 'Preparation is everything'. Interview by Rebecca
      Coombes.

PMID- 11957493
TI  - Tuberculosis. Waging war against 'the white plague'.

PMID- 11957494
TI  - Mental health. Penny-pinching at a cost to patients with schizophrenia.

PMID- 11957495
TI  - Doing it for the kids.

PMID- 11957497
TI  - Should we be getting danger money?

PMID- 11957496
TI  - Does cervical cancer screening do more harm than good?

PMID- 11957498
TI  - Deskbound and bogged down.

PMID- 11957500
TI  - Making daisy chains on ward 42.

PMID- 11957499
TI  - Witness for the prosecution.

PMID- 11957501
TI  - Skilled nurses need more scope.

PMID- 11957502
TI  - Managing chronic pain in children.

PMID- 11957503
TI  - Administration of inotropes.

PMID- 11957504
TI  - A personal cancer ordeal sheds new light on practice.

PMID- 11957506
TI  - Support role spreads the workload in intensive care.

PMID- 11957507
TI  - Learning disabilities and mental ill health: care plans.
AB  - Comprehensive multidisciplinary assessment and treatment are particularly
      important for clients who present with learning disabilities and mental health
      problems (O'Hara and Sperlinger, 1997). This should not be restricted to
      professionals who work in services for people with learning disabilities and
      should include a wider network of professionals from statutory services and the
      independent sector. This arrangement can be complex as different agencies and
      even different departments of the same agency may differ fundamentally in their
      philosophy, vision and understanding of their own and other's roles and
      responsibilities. It is vital that these differences are recognised and dealt
      with so that they do not become a barrier to accessing best practice. Only in
      this way can the person benefit fully and have their needs met.

PMID- 11957508
TI  - Is it possible to prevent falls in frail patients?...

PMID- 11957516
TI  - Virgin on the ridiculous.

PMID- 11957509
TI  - Bone marrow aspiraton and biopsy--1.

PMID- 11957517
TI  - Whistleblowing. Whistle down the wind.

PMID- 11957518
TI  - Cheque, please!

PMID- 11957519
TI  - HIV/AIDS. Time to take your medicine.

PMID- 11957520
TI  - Does PREP still fit the working world of the modern nurse?

PMID- 11957521
TI  - More than a passing fad.

PMID- 11957523
TI  - Health visitors not ready to leave the building.

PMID- 11957522
TI  - Healing the hidden scars.

PMID- 11957524
TI  - Ignore smears against cervical screening.

PMID- 11957525
TI  - Get a headstart into education.

PMID- 11957526
TI  - Nursing helped me cope with my father's death.

PMID- 11957527
TI  - The care homes catastrophe.

PMID- 11957529
TI  - Cry freedom. Interview by Carol Davis.

PMID- 11957528
TI  - Reasons to be cheerful. Genetic diagnosis and therapy are offering hope to people
      with muscular dystrophy.

PMID- 11957530
TI  - As the battle against HIV/AIDS resumes, all nurses are in the front line.

PMID- 11957531
TI  - Smash the 'club culture'.

PMID- 11957532
TI  - Critical care outreach team sees fall in cardiac arrests.

PMID- 11957533
TI  - Improving the management of asthma in under-fives.

PMID- 11957534
TI  - Medication for schizophrenia.

PMID- 11957535
TI  - Sexual health strategy. Nurses key to halting HIV crisis.

PMID- 11957536
TI  - All-party MP group condemns labour's HIV/AIDS strategy.

PMID- 11957537
TI  - Bed rest for acute low back pain and sciatica.

PMID- 11957538
TI  - Specialist nurse leading a small community HIV team.

PMID- 11957539
TI  - The changing face of primary and community health care.

PMID- 11957541
TI  - Bone marrow aspiration and biopsy--2.

PMID- 11957540
TI  - Caffeine addiction and its effects.

PMID- 11957542
TI  - WaIting lists. Targets put before clinical need.

PMID- 11957543
TI  - Disadvantaged women failed by midwives.

PMID- 11957544
TI  - Flu. Jabs for older and at-risk patients.

PMID- 11957545
TI  - Equal pay. Claims deluge expected.

PMID- 11957546
TI  - Should ethical issues in biotechnology research be decided by physician
      scientists or by lawyers?

PMID- 11957547
TI  - Surgical management and outcome of carotid body tumours.
AB  - INTRODUCTION: Carotid body tumours are rare but are interesting in their manner
      of presentation and challenging with respect to surgical extirpation. They may
      present as a neck mass from which a bloody aspirate is obtained on fine needle
      aspiration. They are occasionally diagnosed only at the time of surgery, when one
      encounters the vascular tumour mass. METHODS: We reviewed the results of 8 cases
      operated in our department over a 10-year period from 1989 to 1999. We evaluated
      in-hospital mortality and morbidity, as well as the long-term outcome especially
      with regards to functional disability. RESULTS: Preoperative evaluation included
      angiography, computed tomography (CT) or magnetic resonance angiography.
      Operative technique involves good exposure, vascular control, identification and
      preservation of neurovascular structures and subadventitial tumour dissection. In
      all cases the vagus nerve was preserved, except in 1 case who had a malignant
      tumour and resection of the vagus nerve together with the accessory nerve and
      sympathetic chain. Two patients had unexpected hoarseness of voice
      postoperatively, 1 was due to permanent vagus nerve palsy and the other to
      transient vagus nerve palsy. One of them needed vocal cord medialisation and long
      term tube feeding. One patient had bilateral tumours and developed a stroke after
      an operation on the second tumour. No patients exhibited local or metastatic
      disease during follow-up. There was no mortality in all cases. CONCLUSION:
      Although resection of the carotid body tumour is safe in experienced hands, long
      term morbidity is still a significant problem and can be debilitating to the
      patient.

PMID- 11957548
TI  - Evaluation on the use of a portable unit versus the laboratory for the monitoring
      of International Normalized Ratio (INR) in orally anticoagulated patients.
AB  - INTRODUCTION: Measuring the International Normalized Ratio (INR) through a
      laboratory requires venipuncture and takes about 1 hour for results to be
      available. A portable monitor (CoaguChek Plus System), which measures the INR
      using fingerstick samples, is evaluated in this study to determine its clinical
      significance in anticoagulated and non-anticoagulated individuals. The hospital's
      outpatient and inpatient laboratories were also compared in the study. MATERIALS
      AND METHODS: Paired venous and capillary blood INRs were performed on
      anticoagulated patients using the monitor and the Singapore General Hospital
      (SGH) outpatient and inpatient laboratories (OPS and IPS labs). Paired INRs of
      control samples were also performed using the monitor and the IPS lab. RESULTS:
      We plotted the difference in INR by the 2 methods (monitor and OPS lab, n = 91)
      against their mean, and calculated the limits of agreement (95% of the difference
      would lie between -0.90 to 0.70). After a logarithmic transformation on the data,
      we found that for 95% of the cases, the OPS lab would differ from the monitor by
      13% below to 14% above. There was also a marginal difference (95% limits of
      agreement of -0.14 to 0.10) when we compared the INR obtained from OPS and IPS
      laboratories (n = 43). Our control sample (n = 19) showed that the 95% confidence
      interval for the bias was -0.04 to 0.10. CONCLUSION: The monitor should be used
      with caution in patients with INR > 3. We suggest use of the monitor in
      situations where the non-anticoagulated state of a patient needs to be measured.
      There is a difference in INR measured by laboratories within the same
      institution.

PMID- 11957549
TI  - Cosmesis in neurosurgery: is the bald head necessary to avoid postoperative
      infection?
AB  - AIM: The aims of this study were to prospectively investigate the incidence of
      postoperative wound infection following elective cranial surgery, when scalp hair
      removal was limited to the line of the incision, and to see if there was an
      increased risk of infection. MATERIALS AND METHODS: This is an observational
      study of 57 consecutive adult elective cases operated upon without head shave
      (between July 1998 and December 1998). The method of scalp preparation is
      described. RESULTS: During the follow-up period, there was 1 case (1.75%) of
      postoperative wound infection. This was compared with retrospective data, and was
      not found to be statistically significant. DISCUSSION: In a review of earlier
      studies and a search into the history of aseptic surgery, no scientific ground
      for the practice of shaving was found. We suggest that there is no advantage in
      shaving patients in terms of reducing wound infection rates.

PMID- 11957550
TI  - Emergency laparoscopic surgery--the Changi General Hospital experience.
AB  - INTRODUCTION: This paper analyses the emergency laparoscopic procedures
      undertaken by our unit over a 1-year period in an effort to evaluate the
      diagnostic-therapeutic use of laparoscopy in an emergency situation. MATERIALS
      AND METHODS: This is a retrospective study that analysed 137 emergency
      laparoscopic procedures that were performed for patients who presented with acute
      abdominal pain over a 1-year period from 31 December 1999 to 31 December 2000.
      RESULTS: A definitive diagnosis was made in 91.2% (125). Of the 78 cases that
      required surgical intervention, 71.8% (56) were performed laparoscopically. The
      conversion rate (to open surgery) was 16.8% (23) and the morbidity rate was 8%
      (11); with no mortalities. CONCLUSION: We conclude that laparoscopic surgery is
      effective and safe in the non-elective setting and it offers a high potential for
      diagnosis and therapy in selected patients in whom the diagnoses are equivocal.

PMID- 11957551
TI  - Thyroid surgery--the Tan Tock Seng Hospital otolaryngology experience.
AB  - INTRODUCTION: Central to the management of a patient with a thyroid nodule is the
      evaluation of the risk of malignancy. Postoperative morbidity, though rare,
      remains a concern because of its impact on the quality of the life of the
      patient. MATERIALS AND METHODS: A retrospective audit of 91 consecutive patients
      who underwent thyroid surgery for thyroid nodules, at the Department of
      Otolaryngology, Tan Tock Seng Hospital, between January 1995 and December 2000.
      RESULTS: The sensitivity and specificity of fine-needle aspiration cytology
      (FNAC) were 60% and 100%, respectively. The sensitivity and specificity of
      intraoperative frozen section examination was 82% and 100%, respectively. Sixty
      four patients experienced no postoperative morbidity. Of the 27 patients with
      postoperative morbidity, only 1 was permanent. The incidence of transient and
      permanent biochemical hypocalcaemia was 44% and 0%, respectively. Nodal
      dissection performed together with total thyroidectomy increased the incidence of
      postoperative hypocalcaemia (P < 0.05). The number of parathyroid glands
      preserved in situ did not predict for postoperative hypocalcaemia. The incidence
      of transient and permanent recurrent laryngeal nerve (RLN) palsy was 10.3% and
      1.1% (8.2% and 0.9% of nerves at risk), respectively. Tracheo-oesophageal groove
      clearance performed together with thyroid lobectomy did not increase the
      incidence of postoperative RLN palsy (P > 0.05). The median hospital stay was 3
      days for benign thyroid disease, 4.5 and 16 days for malignant disease with
      tracheo-oesophageal groove clearance only and with neck dissection, respectively.
      CONCLUSION: The combination of clinical examination and FNAC remains the mainstay
      in selecting patients for surgery. Frozen section examination is an important
      intraoperative diagnostic adjunct to decide the extent of surgery. With proper
      surgical training and experience, thyroid surgery for malignancy can be
      undertaken with minimum postoperative morbidity and a short hospital stay.

PMID- 11957552
TI  - Penile colour duplex ultrasonography as a screening tool for venogenic erectile
      dysfunction.
AB  - INTRODUCTION: Vasculogenic impotence is one of the major causes of erectile
      dysfunction. Cavernosometry and cavernosography is traditionally the gold
      standard for evaluation of venogenic impotence. However, it is invasive and there
      are potentially significant complications. Penile colour flow Doppler imaging
      (PCDI) is non-invasive and can be used to assess venous incompetence. MATERIALS
      AND METHODS: One hundred and sixty-eight patients were referred for PCDI
      assessment from March 1998 to February 2001. Forty-three of these also had
      cavernosogram and cavernosometry done and were included in the study. RESULTS:
      The sensitivity was 93.9%, the specificity was 90.0%, the accuracy was 93.0% with
      a negative predictive value of 81.8% and a positive predictive value of 96.9%.
      Kappa value of 0.81 was obtained, indicating excellent agreement between PCDI and
      cavernosogram and cavernometry. CONCLUSIONS: Penile colour flow Doppler imaging
      is accurate in the assessment of venogenic erectile dysfunction. It can replace
      cavernometry and cavernosogram as a screening tool. Cavernometry and
      cavernosogram should only be done in cases when PCDI suggests venogenic
      impotence, and when surgery is contemplated.

PMID- 11957553
TI  - Bullous pemphigoid seen at the National Skin Centre: a 2-year retrospective
      review.
AB  - INTRODUCTION: Bullous pemphigoid (BP) is the most common immunobullous disorder
      in Western Europe, affecting mainly the elderly. Previous reports have suggested
      that it is rarer in the Far East. We report on the clinico-epidemiological
      features of BP seen at our centre. MATERIALS AND METHODS: This is a 2-year
      retrospective study of patients seen at the National Skin Centre who were
      diagnosed to have BP. RESULTS: Fifty-nine patients were newly diagnosed with BP
      over a 2-year period between January 1998 and December 1999. The minimum
      estimated incidence was 7.6 per million population per year, with mean age of
      onset of 77 years, and a male to female ratio of 1:2. There was a predilection
      for Chinese but not Indian. Localised disease was found in 34% and mucosal
      involvement in only 1.7%. Direct immunofluorescence was positive in almost all
      patients, and 94% of those tested had positive indirect immunofluorescence.
      'Roof' pattern was present in 95.8% and 'roof and floor' pattern in 4.2%.
      Prednisolone was the treatment of choice in most patients (78%). Anti
      inflammatory agents were more commonly used than a decade ago (13.5%).
      CONCLUSIONS: BP is the most common immunobullous disease locally, with an
      incidence at least equal to that in Western Europe. There was a predilection for
      ethnic Chinese rather than Indian. Apart from the rarity of mucosal involvement,
      the clinical features are similar to those of Western nations.

PMID- 11957554
TI  - Four-month chemotherapy in the treatment of smear-negative pulmonary
      tuberculosis: results at 30 to 60 months.
AB  - INTRODUCTION: Most patients with active pulmonary tuberculosis (PTB) are treated
      with a 6-month short course regimen. The purpose of the present study was to
      assess the efficacy of using 4 months of chemotherapy to treat patients with
      smear-negative PTB. METHODS: A total of 314 patients were randomised to a daily
      or combined (daily and intermittent) regimen as follows: (1) 2HRZ/2HR--2 months
      of isoniazid (H), rifampicin (R) and pyrazinamide (Z), followed by 2 months of H
      and R or (2) 2HRZ/2H3R3--2 months of HRZ as in regimen 1, followed by H and R
      given 3 times weekly for 2 months or 4 months if initial sputum specimens were
      culture positive. RESULTS: One hundred and fifty-eight patients were assigned to
      the daily regimen and 156 to the combined regimen. Of the 158 patients, 99 had
      negative cultures and 59 had positive cultures. There was no relapse among 96
      culture-negative patients assessed at 30 months and 68 patients at 60 months.
      However, 6 patients had no radiological response while 1 was considered on review
      to have non-tuberculous disease. There was no relapse among 57 culture-positive
      patients assessed at 30 months and 41 at 60 months. In the combined regimen
      group, 102 had negative cultures and 54 had positive cultures. There was 1
      relapse in the culture-negative group of 100 patients assessed at 30 months and
      74 at 60 months. There was no radiological response in 5 patients. One patient in
      the culture-positive group failed therapy but there were no relapses during
      follow-up to 60 months. CONCLUSION: A 4-month daily or combined regimen appears
      to be highly effective in the treatment of non-immunocompromised patients with
      smear- and culture-negative PTB.

PMID- 11957555
TI  - Influenza in Singapore: assessing the burden of illness in the community.
AB  - INTRODUCTION: Influenza infection has significant morbidity and mortality. The
      social and economic costs from work absence in the working population and from
      hospitalisations in the elderly are considerable. Meta-analyses of cohort and
      randomised controlled studies indicate that influenza vaccination is effective in
      preventing respiratory illness, hospitalization, pneumonia and death in 50% to
      68% of cases. In Singapore, data on the disease burden from influenza are sparse
      and no official recommendation on influenza vaccination exists. METHOD: We
      estimated the disease burden of influenza-like illness (ILI), influenza infection
      in the general adult population, and hospitalisations and deaths from pneumonia
      and influenza, from routine official and published sources, and hoc community
      sample surveys, national virological surveillance, hospitalization and mortality
      data. RESULTS: In a resident population of 3 million people, there were 4.2
      million cases of ILI in a typical non-epidemic year, 3.5 million visits to the
      doctor and 2.1 million days of work absence due to ILI. Data from the National
      Influenza Surveillance Programme indicated that about 15% of patients with ILI
      were positive for influenza isolates. We therefore estimated 630,000 cases of
      influenza virus infection cases a year, giving rise to 520,000 sick visits and
      315,000 days of sick absence from work. About 4200 elderly (65+) persons were
      hospitalised for pneumonia and influenza, resulting in about 1450 deaths every
      year. The literature suggests a vaccine efficacy of about 50% of preventing
      influenza and its complications, including hospitalizations and deaths. This
      indicates that at least 315,000 cases of influenza virus infection, 258,000 sick
      visits, and 157,000 lost days from work in the whole population, and 2100
      hospitalisations and 600 deaths from pneumonia in the elderly are potentially
      preventable by vaccination each year. CONCLUSION: Influenza poses a considerable
      burden of illness in the community and the potential benefits from influenza
      vaccination are substantial.

PMID- 11957556
TI  - Comparing fasting plasma glucose against two-hour post-load glucose
      concentrations for the diagnosis of diabetes mellitus and glucose intolerance in
      Singaporean hospital patients.
AB  - INTRODUCTION: Several studies have assessed the impact of the 1997 American
      Diabetes Association (ADA) recommendation, of using fasting plasma glucose (FPG)
      concentration, to diagnose diabetes mellitus in population-based cohorts.
      However, data concerning the impact of this recommendation in the hospital
      setting are limited. As the performance characteristics of diagnostic tests vary
      depending on the prevalence of diabetes in the population studied, we have
      examined the clinical impact of adopting the ADA recommendations in comparison to
      the traditional 2-hour post-load glucose (2HPG) concentration used by the World
      Health Organisation (WHO) in diagnosing diabetes and other categories of glucose
      intolerance in Singaporean hospital patients. MATERIALS AND METHODS: We analysed
      the results of the standard 75 g oral glucose tolerance test (OGTT) performed on
      625 patients in our hospital from 1994 to 1999. RESULTS: The prevalence of
      diabetes amongst these 625 patients was 36.8% (230) based on the ADA
      recommendation of using FPG, 42.8% (263) on using the 2HPG and 52.0% (325) on
      using the full 1998 WHO criteria. The degree of agreement (kappa) in establishing
      the diagnosis of diabetes between the FPG and 2HPG cut-offs was 0.48. Ninety-five
      (15.2%) individuals had diabetes based on the 2HPG alone, 62 (9.9%) based on the
      FPG alone and 168 (26.9%) based on both the FPG and 2HPG. Eighty-six (13.8%)
      individuals had impaired fasting glucose (IFG) and 123 (19.7%) had impaired
      glucose tolerance (IGT). The kappa-value between IFG and IGT was 0.08.
      CONCLUSION: Fasting plasma glucose concentration was an inadequate parameter in
      diagnosing diabetes and intermediate categories of glucose intolerance in our
      cohort of subjects. Our findings suggest that the OGTT remains an important
      diagnostic tool for classifying glucose tolerance in our hospital patients.

PMID- 11957557
TI  - Technetium-99m methoxyisobutylisonitrile imaging in the follow-up of
      differentiated thyroid carcinoma.
AB  - OBJECTIVE: To evaluate the potential of technetium-99m methoxyisobutylisonitrile
      (Tc-99m MIBI) imaging as an alternative to I-131 total-body scan (I-131 TBS) for
      the follow-up of patients with differentiated thyroid carcinoma (DTC). PATIENTS
      AND METHODS: We performed 87 Tc-99m MIBI imaging studies in 76 DTC patients who
      had total or near-total thyroidectomy followed by a radioactive iodine ablation
      while receiving thyroxine therapy. The final diagnosis was correlated with I-131
      TBS, serum thyroglobulin (Tg), other conventional imaging modalities, clinical
      outcome, and/or pathological report. RESULTS: Seventy-six recurrent tumours or
      metastatic conditions in 58 DTC patients were detected. The overall findings of
      Tc-99m MIBI showed 72% sensitivity, 100% specificity and 77% accuracy. The
      figures for I-131 scan were 57%, 100% and 66%, respectively. When classifying
      upon tumour locations, Tc-99m MIBI imaging had sensitivity of 79% for cervical,
      50% for mediastinal, 65% for skeletal and 69% for pulmonary metastases and the
      corresponding values for I-131 TBS were 33%, 67%, 94% and 75%, respectively.
      Furthermore, Tc-99m MIBI could detect only 44% of thyroid remnants demonstrated
      by radioiodine scan. CONCLUSIONS: Tc-99m MIBI imaging is more sensitive than I
      131 TBS in detecting tumours in the neck but less sensitive for metastasis
      elsewhere, as well as thyroid remnants. Therefore, Tc-99m MIBI imaging should not
      substitute but rather complement I-131 TBS for evaluation of DTC patients post
      radioiodine ablation.

PMID- 11957558
TI  - Two-year outcome of normal-birth-weight infants admitted to a Singapore neonatal
      intensive care unit.
AB  - INTRODUCTION: To describe the characteristics, the immediate and short-term
      outcome and predictors of mortality in normal-birth-weight (NBW) infants admitted
      to a tertiary neonatal intensive care unit (NICU) in Singapore. MATERIALS AND
      METHODS: We retrospectively reviewed the medical records of 137 consecutive NBW
      infants admitted to the NICU of the Singapore General Hospital from January 1991
      to December 1992. Data on the diagnoses, clinical presentation of illness,
      intervention received, complications and outcome as well as follow-up patterns
      for the first 2 years of life, were collected and analysed. RESULTS: NBW NICU
      infants comprised 1.8% of births in our hospital and 40.8% of all NICU
      admissions. The main reasons for NICU admissions were respiratory disorders
      (61.3%), congenital anomalies (15.3%) and asphyxia neonatorum (11.7%).
      Respiratory support was necessary in 81.8%. Among those ventilated, the only
      predictive factor contributing to mortality was the mean inspired oxygen
      concentration. The mortality rate was 11.7%. Causes of death included congenital
      anomalies (43.75%), asphyxia neonatorum (31.25%) and pulmonary failure secondary
      to meconium aspiration syndrome (12.5%). The median hospital stay among survivors
      (88.3%) was 11.0 (range, 4 to 70) days. Of 42 patients (out of 117 survivors) who
      received follow-up for at least 6 months, 39 infants did not have evidence of any
      major neurodevelopmental abnormalities at their last follow-up visit, prior to or
      at 2 years of age. CONCLUSIONS: Despite their short hospital stay (compared to
      very-low-birth-weight infants), the high volume of NBW admissions make the care
      of this population an important area for review to enhance advances in and hence,
      reduce the cost of NICU care. With improved antenatal diagnostic techniques
      (allowing earlier and more accurate diagnosis of congenital malformations) and
      better antenatal and perinatal care (allowing better management of at-risk
      pregnancies), it is anticipated that there should be a reduction in such
      admissions with better outcomes. Close follow-up of this high-risk group of
      infants is also important in order to offer early intervention to those who may
      possibly have perinatally-related developmental difficulties.

PMID- 11957559
TI  - Paediatric extracranial germ cell tumours: a retrospective review.
AB  - INTRODUCTION: Germ cell tumours (GCTs) are rare, constituting 3% of all childhood
      malignancies. The aim of this study was to analyse the epidemiology and outcome
      of these patients. MATERIALS AND METHODS: A retrospective, cohort study was
      conducted on 38 paediatric patients presenting with extracranial GCTs, treated at
      the Singapore General Hospital, Tan Tock Seng Hospital and Kandang Kerbau Women's
      and Children's Hospital from 1 January 1989 to 30 June 1999. The median age at
      diagnosis was 1.7 years (0 to 13 years). RESULTS: There was no sex or racial
      preponderance. Eighteen patients (47.3%) had teratomas, 16 (42.1%) had yolk sac
      tumours, 1 (2.6%) had dysgerminoma and 3 (7.9%) had mixed GCTs. Thirty-four
      patients (89.5%) had Stage I disease, 1 (2.6%) had Stage II disease, 1 (2.6%) had
      Stage III disease and 2 (5.3%) had metastatic disease. Complete tumour resection
      was achieved in 36 of the 38 patients (95%). Cisplatin-based combination
      chemotherapy was given to 11 patients (28.9%). None of the patients received
      radiotherapy. Complications from chemotherapy included anaemia requiring packed
      red cell transfusion (n = 3), Port-a-cath sepsis requiring removal (n = 1),
      febrile neutropenia (n = 1) and nephropathy (n = 1). CONCLUSION: Using the Kaplan
      Meier life tables, the overall and event-free survivals at 10 years for the
      patients with malignant GCTs were 96% and 88%, respectively, with a mean follow
      up period of 5.1 years (0.7 to 10 years). The majority of the patients presented
      with early Stage I disease and this contributed to our high survival rate.

PMID- 11957560
TI  - The role of BTA stat in clinical practice.
AB  - OBJECTIVE: BTA stat is a rapid, urine-based test for bladder cancer that detects
      human complement factor H related protein (HCFHrp) by monoclonal assay. This aim
      of this study was to assess the efficacy of BTA stat as a diagnostic tool for
      bladder cancer in symptomatic patients suspected of bladder cancer and in the
      surveillance of patients with a history of treated bladder cancer. PATIENTS AND
      METHODS: One hundred and six patients presenting with haematuria (gross or
      microscopic) or irritative bladder symptoms presenting to the urology outpatient
      clinic of Changi General Hospital and 13 patients under bladder cancer
      surveillance were recruited for this prospective study. All underwent voided
      urine cytology (VUC), urine culture, urine BTA stat, intravenous urogram and
      cystoscopy. Sensitivity, specificity, positive and negative predictive values
      were calculated for both tests. The stage and grade of bladder tumours detected
      were also correlated with both test results. Causes of false positives and
      specificity in different patient groups were analysed. RESULTS: BTA stat is more
      sensitive than VUC in detecting primary and recurrent bladder tumours (85% versus
      55%) but is less specific (62.6% versus 100%). Urinary tract infections and
      urinary calculi accounted for 62% of false positives with BTA stat. When patients
      with positive urine cultures and benign IVU abnormalities were excluded,
      specificity of BTA stat improved (93.9% cf. 62.6%). BTA stat was highly specific
      (100%) and more sensitive than VUC (75% versus 25%) in detecting recurrent
      tumours in asymptomatic patients on cancer surveillance. CONCLUSION: A high false
      positive rate and low predictive value limits the use BTA stat in screening
      symptomatic patients. However, it has a role in cancer surveillance and in the
      screening of high-risk asymptomatic individuals. Further prospective trials
      should be performed to better assess its role in this respect.

PMID- 11957561
TI  - Current status in the surgical management of adult polycystic liver disease.
AB  - INTRODUCTION: In patients with adult polycystic liver disease (APLD), there is
      considerable debate surrounding the most effective way of managing symptomatic
      cysts. Conservative approaches like percutaneous aspiration or cyst fenestration
      are associated with low morbidity but high recurrence rates. Conversely, liver
      resection and hepatectomy with orthotopic liver transplantation is drastic and
      associated with high morbidity and mortality rates. Our aim is to review the
      current understanding of liver cystogenesis in these patients and the therapeutic
      options available in order to provide a rationale guide to management of this
      intriguing condition. METHODS: This article summarises the findings of published
      papers in major international journals indexed on MEDLINE on APLD using the key
      words--adult polycystic liver disease, liver cysts, fenestration, liver
      resection, liver transplantation and polycystic kidney disease. The period of
      search includes papers between 1965 and 2000. RESULTS: Published studies have
      suggested a 'two-hit' hypothesis to explain the development of liver cysts in
      patients with APLD. This will provide the rationale for future management.
      Meanwhile, the indications, pitfalls and results of the various therapeutic
      options are reviewed. Management of symptoms has to be tailored to the underlying
      severity of the liver cystic disease, co-morbidity and procedural risks and
      recurrence rates. CONCLUSION: Good long-term relief of symptoms can be achieved
      with the correct procedure at acceptable morbidity and mortality rates. We have
      provided guidelines on the various options available to enable a structured
      approach to the management of APLD.

PMID- 11957562
TI  - Anaesthetic considerations for lung volume reduction surgery--a case report.
AB  - INTRODUCTION: This case describes some of the unique problems faced by the
      thoracic anaesthesiologists during anaesthesia for lung volume reduction surgery.
      CLINICAL PICTURE: The usual pulmonary function requirements for lobectomy are
      normally not met in these patients with severe emphysema. TREATMENT: Maintenance
      of the functional residual capacity of the lung and normocapnia during
      anaesthesia are not as important. Instead problems due to barotrauma and dynamic
      hyperinflation from positive pressure ventilation are. OUTCOME: Modification of
      ventilation strategy and providing an anaesthetic tailored towards early
      extubation is the cornerstone of the anaesthetic plan. CONCLUSION: A good
      understanding of the respiratory physiology in patients with severe emphysema is
      essential.

PMID- 11957563
TI  - Adrenal myelolipoma presenting with spontaneous retroperitoneal haemorrhage
      demonstrated on computed tomography and angiogram--a case report.
AB  - INTRODUCTION: A rare case of adrenal myelolipoma presenting with spontaneous
      rupture and retroperitoneal haemorrhage is described. CLINICAL PICTURE: A 51-year
      old Caucasian male presented with acute onset of right loin pain. Preliminary
      diagnosis of haemorrhagic adrenal tumour was made on computed tomography (CT) and
      angiography. TREATMENT: Vascular embolisation was performed to stabilise the
      patient prior to definitive surgery. Tumour resection was subsequently performed.
      Histology confirmed ruptured adrenal myelolipoma. OUTCOME: The patient made an
      uneventful recovery. CONCLUSION: Ruptured adrenal myelolipoma should be
      considered in cases of spontaneous retroperitoneal haemorrhage. Vascular
      embolisation may be useful in stabilising the patient prior to definitive
      surgery.

PMID- 11957564
TI  - Allopurinol hypersensitivity syndrome and acute myocardial infarction--two case
      reports.
AB  - INTRODUCTION: Allopurinol hypersensitivity syndrome is an idiosyncratic drug
      reaction characterised by an acute and severe multiorgan disease. It usually
      begins 2 to 6 weeks after starting allopurinol. The most important and critical
      characteristics are the presence of visceral involvement and haematological
      abnormalities; hepatitis, interstitial nephritis and eosinophilia are most
      frequently seen. However, cardiac involvement has not been previously reported.
      CLINICAL PICTURE: Two previously well young Chinese men presented with fever,
      rash and hepatitis 3 weeks after taking allopurinol. The clinicopathological
      presentation was typical of allopurinol hypersensitivity syndrome. TREATMENT AND
      OUTCOME: Both men received systemic corticosteroid therapy and had full recovery.
      A few months later, they each had an acute myocardial infarction with a fatal
      outcome, despite minimal cardiac risk factors and no family history of coronary
      artery disease. CONCLUSION: The immunologic process in allopurinol
      hypersensitivity syndrome may have caused coronary vasculitis and subsequent
      myocardial infarct. Alternatively, the idiosyncratic reaction may have damaged
      myocardium, with the resultant myocarditis masquerading as coronary artery
      disease. Patients with allopurinol hypersensitivity syndrome should be followed
      up for cardiac involvement.

PMID- 11957565
TI  - Visual rehabilitation with new-age rigid gas-permeable scleral contact lenses--a
      case series.
AB  - INTRODUCTION: Primary ectatic corneal diseases usually require rigid gas
      permeable (RGP) corneal contact lens wear for visual rehabilitation. As the
      disease progresses, it becomes increasingly difficult to fit these lenses. RGP
      scleral contact lenses now provide another treatment option before resorting to
      surgery. CLINICAL PICTURE: Two patients with pellucid marginal degeneration and
      one with advanced keratoconus had failed treatment with conventional lenses.
      TREATMENT: They were fitted with RGP scleral lenses. OUTCOME: Good vision was
      obtained together with satisfactory fit and comfort. CONCLUSION: RGP scleral
      lenses are a viable alternative to surgery in the visual rehabilitation of
      patients with advanced ectatic corneal disorders.

PMID- 11957566
TI  - Unusual endolaryngeal extension of a large thyroglossal duct cyst.
AB  - INTRODUCTION: Thyroglossal duct cysts account for approximately 70% of congenital
      neck abnormalities. Hoarseness of voice and the extension of the cyst into the
      larynx are very uncommon. CLINICAL PICTURE: We present a patient with a long
      history of a large thyroglossal cyst who developed progressive hoarseness of
      voice. The cyst had protruded into the larynx producing the appearance of a
      laryngeal neoplasm. Computed tomography (CT) clearly demonstrated the nature of
      the cyst and its encroachment into the larynx. TREATMENT: This was safely excised
      with a Sistrunk procedure and a temporary tracheostomy to maintain a secure
      airway, in view of the possibility of postoperative supraglottic oedema.
      CONCLUSION: Endolaryngeal extension of the thyroglossal duct cyst is rare.
      Evaluation of unusual large midline neck masses should include a CT scan. The
      intralaryngeal component of the cyst can be easily dissected off from the
      neighbouring structures during dissection in the Sistrunk procedure. A
      tracheostomy may be needed.

PMID- 11957567
TI  - Case report on recombinant coagulation factor VIIa in the treatment of three
      haemophilia A patients with inhibitors in Singapore.
AB  - INTRODUCTION: We report the first experiences with use of recombinant coagulation
      Factor VIIa (rFVIIa) in the treatment of haemophilia A patients with inhibitors
      in Singapore and discuss observations in 3 patients. CLINICAL PICTURE: Case 1
      bled on two separate occasions into his neck muscles and vocal cord. Case 2 had
      gross haematuria from bleeding in the renal calyxes. Case 3 bled into the parotid
      muscles. TREATMENT: rFVIIa in doses, ranging from 50 ug/kg to 90 ug/kg, at
      different dosing intervals, were used. OUTCOME: Excellent responses were seen in
      doses of 70 and 90 ug/kg. CONCLUSIONS: rFVIIa is highly effective, both
      clinically and cost-wise, in the treatment of these patients.

PMID- 11957568
TI  - Statins and bone morphogenetic proteins: new pathways in bone formation.
AB  - INTRODUCTION: Osteoporosis is a major public health problem leading to morbidity
      and mortality in many individuals. Treatment for osteoporosis has generally
      relied on mechanisms that decrease osteoclastic bone resorption. This review
      outlines new evidence that the cholesterol synthetic pathway may be important in
      bone metabolism and that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors or statins may increase bone formation. RESULTS: An
      experimental observation reported that statins increase bone formation in rodents
      and that statins have an important role for the cholesterol synthetic pathway in
      bone formation. This may be via potent bone-forming growth factors, the bone
      morphogenetic proteins (BMPs). Subsequent epidemiological studies (including a
      meta-analysis of 8 studies) have suggested that statin use may be associated with
      increased bone mineral density (BMD) and decreased fracture risk in humans.
      However, more recently published studies have challenged the effect on fracture
      risk. CONCLUSION: The effect of statins on bone mineral density and fracture risk
      in retrospective studies suggests an exciting new direction for research in bone
      formation that may lead to advances in the therapy of osteoporosis.

PMID- 11957569
TI  - Clinical update on deep vein thrombosis in Singapore.
AB  - Venous thromboembolism (VTE) is thought to be a rare occurrence in Asian
      patients. The clinical features of VTE are elusive and the disease often
      unsuspected. Objective testing such as the duplex ultrasound scans and pulmonary
      imaging are necessary as clinical diagnosis alone is inaccurate. Fatality can
      occur in untreated patients not suspected of the disease as shown by our post
      mortem studies. Indeed VTE is one of the leading causes of maternal mortality in
      Singapore. There is a rising trend in the incidence of VTE in Asia. Initial
      studies found an incidence of about 3 per 10,000 hospital admissions in Hong Kong
      and Malaysia in 1988 and 1990, respectively; rising to 8 and 15.8 per 10,000
      hospital admissions in Singapore 1992 and 2000, respectively. The major risk
      factors for developing deep vein thrombosis (DVT) in our patients are
      immobilisation, surgery and malignancy. While Factor V Leiden mutation and
      mutation at position 20,210 in the prothrombin gene are found to be extremely
      rare in Chinese, the rest of the thrombophilia has not been formally studied.
      Studies in Singapore reported rates of 3% to 7% of DVT after general surgery,
      9.7% after hip surgery and 14% after total knee replacement surgery. It is
      difficult to compare with studies from other centres because of differences in
      patient selection and diagnostic criteria. Studies in Singapore showed that the
      use of prophylactic low molecular weight heparin completely abolished the
      occurrence of DVT for patients undergoing total knee replacement and colorectal
      surgery without an increase in bleeding complications. In conclusion, VTE is not
      an uncommon problem here. Major acquired risk factors do not differ from the
      Caucasian populations. VTE is a preventable disease and a better understanding of
      its epidemiology, patient-risk factors and biological factors will allow better
      management of this condition.

PMID- 11957570
TI  - Clinical update on managing the obstructed airway.
AB  - The upper airway can obstruct due to soft tissues, blood, secretions and
      infections. In patients who are sedated, anaesthetised or unconscious, the
      commonest cause is due to loss of airway muscle tone. The usual site of
      obstruction is the soft palate followed by the epiglottis and occasionally the
      tongue. To relieve the obstruction, a head tilt, chin lift jaw thrust and open
      mouth manoeuvre should be performed. This will tense the muscles in the floor of
      the mouth causing the hyoid and larynx to be lifted away from the posterior
      pharyngeal wall. Oral and nasal airways are useful adjuncts to improve airway
      patency. In patients who are unconscious or adequately anaesthetised, the
      laryngeal mask or Combitube could be used especially in the difficult airway
      situation. As there is a significant decline in performance with time, it is
      important to maintain airway skills through regular practice and evaluation.

PMID- 11957571
TI  - The search for what is fundamental in the development of working memory.

PMID- 11957572
TI  - Schooling as cultural process: working together and guidance by children from
      schools differing in collaborative practices.

PMID- 11957573
TI  - Beyond prototypes: asymmetries in infant categorization and what they teach us
      about the mechanisms guiding early knowledge acquisition.

PMID- 11957574
TI  - Peer relations in the transition to adolescence.

PMID- 11957575
TI  - Culture, autonomy, and personal jurisdiction in adolescent-parent relationships.

PMID- 11957576
TI  - Maternal responsiveness and early language acquisition.

PMID- 11957577
TI  - Ethnic health. Relative values.

PMID- 11957578
TI  - Child mental health. An end to innocence.

PMID- 11957579
TI  - Welsh NHS. We will go our own way.

PMID- 11957580
TI  - Nursing education. Who's failing whom?

PMID- 11957581
TI  - Should the NHS buy failing nursing homes?

PMID- 11957582
TI  - Nursing is sinking without trace.

PMID- 11957583
TI  - Time to out the lack of gay research.

PMID- 11957584
TI  - The painful birth of a new television genre.

PMID- 11957585
TI  - Whatever happened to amenity beds?

PMID- 11957586
TI  - Is my nursing home exploiting me?

PMID- 11957587
TI  - How to get the job you want.

PMID- 11957588
TI  - Lives less ordinary.

PMID- 11957589
TI  - End the turf war to lighten our load.

PMID- 11957590
TI  - Subarachnoid haemorrhage: managing complications.

PMID- 11957591
TI  - Paediatric discharge criteria lead to improved outcomes.

PMID- 11957592
TI  - Using video recording in observational research.

PMID- 11957593
TI  - Making the most of modern matron.

PMID- 11957594
TI  - Telemedicine versus face to face patient care: effects on professional practice
      and health care outcomes.

PMID- 11957595
TI  - How can we encourage this group of patients to eat and what methods can we use to
      stimulate their appetites?

PMID- 11957596
TI  - Breathing tube equipment. Nurse discovers fifth blockage.

PMID- 11957597
TI  - Patient death. Anonymous calls brand nurses as 'murderers'.

PMID- 11957598
TI  - Staff retention. Poor management is major reason for quitting.

PMID- 11957599
TI  - Managing extravasation injuries in preterm neonates.

PMID- 11957600
TI  - Non-healing leg ulceration.

PMID- 11957602
TI  - Vacuum-assisted closure.

PMID- 11957603
TI  - Traumatic wounds: local wound management.

PMID- 11957604
TI  - Reactions to topical medicaments and wound care products.

PMID- 11957605
TI  - A practical guide to managing coursework.

PMID- 11957606
TI  - Cancer services. Breast drain pilot success.

PMID- 11957607
TI  - Drug errors. Numberplate ID aims to reduce mistakes.

PMID- 11957608
TI  - Changing of the guard.

PMID- 11957609
TI  - International Network of Nurse Practitioners and Advanced Practice Nurses'
      conference. A world of difference.

PMID- 11957610
TI  - Mental health. Talk of a lay-off.

PMID- 11957612
TI  - Now I'm qualified I need training.

PMID- 11957611
TI  - Cooking up a choice NHS.

PMID- 11957613
TI  - Ageing population needs homes.

PMID- 11957614
TI  - Positive optimism for a big profession.

PMID- 11957615
TI  - Is it irresponsible to encourage young people to go into nursing?

PMID- 11957616
TI  - The barrier to talking honestly about sex.

PMID- 11957618
TI  - Holidays from hell.

PMID- 11957617
TI  - Can I move from nursing to midwifery?

PMID- 11957619
TI  - Bodies in motion, minds at rest.

PMID- 11957620
TI  - Managing the confused patient.

PMID- 11957621
TI  - A health care system in need of foreign recruits should be a friend in deed.

PMID- 11957622
TI  - Psychiatric Lara Crofts? Forget it.

PMID- 11957623
TI  - Recognising the causes of delirium in older people.

PMID- 11957624
TI  - Tackling aggression with oestrogen.

PMID- 11957625
TI  - Dying with dignity.

PMID- 11957626
TI  - House dust mite control measures for asthma.

PMID- 11957627
TI  - The rheumatology community nurse.

PMID- 11957628
TI  - A systematic desensitisation programme for agoraphobia.

PMID- 11957629
TI  - Legal threat to means tested nursing care.

PMID- 11957630
TI  - We should value the core skills.

PMID- 11957631
TI  - How can I ensure that clients who go to prison have their mental health needs
      addressed.

PMID- 11957632
TI  - Mental health rehabilitation.

PMID- 11957633
TI  - Red-tape warning on appeals to super regulator.

PMID- 11957634
TI  - Working conditions. RCN rescues Filipino nurses from bullies.

PMID- 11957636
TI  - Clinical errors. Nurse condemns reuse of equipment to cut costs.

PMID- 11957635
TI  - Heart Hospital. Transferred nurses will be paid more than NHS staff.

PMID- 11957637
TI  - Health and safety. New evidence reveals scale of latex glove allergies.

PMID- 11957638
TI  - Vaccination. Nurse anxiety after GMC charges doctor over single-dose MMR jabs.

PMID- 11957639
TI  - Public-private partnerships. Thin end of the wedge?

PMID- 11957640
TI  - Patient counselling. Talking points.

PMID- 11957641
TI  - An everyday story of abuse.

PMID- 11957642
TI  - Alcohol units: 14 (v.v. bad).

PMID- 11957644
TI  - Tired and emotional.

PMID- 11957643
TI  - Heart in the right place.

PMID- 11957645
TI  - Our 'job' is unique and packs an emotional punch.

PMID- 11957646
TI  - Are integrated care pathways suitable for maternity care?

PMID- 11957647
TI  - When can nurses be charged with manslaughter?

PMID- 11957648
TI  - When it's time to go home.

PMID- 11957649
TI  - A nation of pill poppers?

PMID- 11957650
TI  - Nursing abroad. Care force landings.

PMID- 11957652
TI  - Planning for a smooth discharge.

PMID- 11957651
TI  - Harsh lesson for our teachers.

PMID- 11957653
TI  - A holistic approach to pain.

PMID- 11957654
TI  - Nursing a patient after subarachnoid haemorrhage.

PMID- 11957655
TI  - Homeward bound.

PMID- 11957657
TI  - Missing student's family hits out at nursing college.

PMID- 11957656
TI  - Who will hold the reins of power?

PMID- 11957659
TI  - Several infusion pumps in regular use that I have not encountered before. What
      should I do?

PMID- 11957658
TI  - Digitalis for treatment of congestive heart failure in patients in sinus rhythm.

PMID- 11957660
TI  - Specialists must share knowledge.

PMID- 11957661
TI  - Respiratory nurse consultant: the role.

PMID- 11957662
TI  - Lifesaver or life sentence?

PMID- 11957663
TI  - Patients with severe asthma.

PMID- 11957665
TI  - Lecturer struck off after claiming child pornography was a teaching aid.

PMID- 11957664
TI  - Air tube inquiry shifts focus to health staff.

PMID- 11957666
TI  - Pulmonary hypertension: the role of specialist units.

PMID- 11957667
TI  - A non-pharmacological approach to managing breathlessness.

PMID- 11957668
TI  - Nurse bitten by patient with HIV is back at work.

PMID- 11957669
TI  - Staff retention. Staying power.

PMID- 11957671
TI  - Infection control. 'We've not seen the worst of CJD yet'.

PMID- 11957670
TI  - Profile. Children's champion.

PMID- 11957672
TI  - Is the older people's lobby harming younger people's care?

PMID- 11957673
TI  - What's in a name?

PMID- 11957674
TI  - Degrees of stupidity.

PMID- 11957675
TI  - Brassed off with knee-jerk reactions.

PMID- 11957677
TI  - From busy wards to silly walks. Interview by Carol Davis.

PMID- 11957676
TI  - Hey big spender.

PMID- 11957678
TI  - A breath of fresh air.

PMID- 11957679
TI  - Bringing the bullies to book.

PMID- 11957681
TI  - A vicious circle: visual impairment in people with learning disabilities.

PMID- 11957680
TI  - Osteoarthritis: symptoms and nursing management.

PMID- 11957682
TI  - Victim or villain? Why trusts must overhaul complaints procedures.

PMID- 11957683
TI  - Understanding empowerment.

PMID- 11957684
TI  - Racism in nursing: a critical realist approach.

PMID- 11957685
TI  - Antibiotics for sore throat.

PMID- 11957686
TI  - Review to evaluate the effectiveness of nurse led clinic.

PMID- 11957687
TI  - Bone marrow aspiration and biopsy--3.

PMID- 11957688
TI  - Nutrition and learning disabilities.

PMID- 11957689
TI  - Drug errors. Nurse's death leads to electronic prescribing.

PMID- 11957690
TI  - Energy balance, mood and behaviour.

PMID- 11957691
TI  - Hyperemesis gravidarum: a short case study.

PMID- 11957692
TI  - Best practice in weaning.

PMID- 11957693
TI  - Osteoporosis.

PMID- 11957695
TI  - Mental health. Lay workers 'better than nurses'.

PMID- 11957694
TI  - Violence an 'everyday occurrence' in trust.

PMID- 11957696
TI  - Comeback on the cards for home dialysis.

PMID- 11957697
TI  - Nurse prescribing. 200-plus nurse formulary out for consultation.

PMID- 11957698
TI  - Patient dissatisfaction. Survey reflects staff shortages, say midwives.

PMID- 11957699
TI  - Watchdog's verdict: millions squandered, nurses neglected.

PMID- 11957700
TI  - Chaos, error and fraud costing NHS millions.

PMID- 11957701
TI  - 800m pounds: the government's incentive to end NHS reliance on agency nurses.

PMID- 11957702
TI  - Nurses get ready for TV stardom.

PMID- 11957704
TI  - A step back for rehab.

PMID- 11957705
TI  - Testing body and spirit in a very uncivil war.

PMID- 11957706
TI  - Should patients with dementia be told their diagnosis?

PMID- 11957707
TI  - How do I speak up about bad practice?

PMID- 11957708
TI  - Adding insult to injury.

PMID- 11957709
TI  - Love, sweat, tears (and a little shaving foam).

PMID- 11957711
TI  - Dealing with the facts of life.

PMID- 11957710
TI  - Inspiring a new generation.

PMID- 11957712
TI  - You just keep me hanging on.

PMID- 11957714
TI  - Are lecturers keeping up with their PREP?

PMID- 11957713
TI  - How to delegate your way to a better working life.

PMID- 11957715
TI  - Developing patient group directions.

PMID- 11957716
TI  - Reaching the heart of the community.

PMID- 11957717
TI  - Covert medication. UKCC 'not willing' to justify hidden drugs.

PMID- 11957718
TI  - Sleep patterns in older people.

PMID- 11957720
TI  - Improving practice with limited resources.

PMID- 11957719
TI  - Assessing leadership development training.

PMID- 11957721
TI  - Herbal and dietary therapies for primary and secondary dysmenorrhoea.

PMID- 11957722
TI  - White students twice as likely to get nursing places.

PMID- 11957723
TI  - Whistleblowing. Weak system let GP abuse.

PMID- 11957724
TI  - Improved procedure for private sector patients.

PMID- 11957725
TI  - 'Black hole' hides criminal past.

PMID- 11957726
TI  - Sexual health. Policy vacuum blamed for STI rise.

PMID- 11957727
TI  - Physicians and fund development. Overcoming the objections.

PMID- 11957728
TI  - The greatest gift. A reminder of the true meaning of fund development.

PMID- 11957729
TI  - At the end of the continuum--"going home". Health care needs to focus on
      providing hospice services to the communities they serve.

PMID- 11957730
TI  - Bonfils' special event. Outreach and awareness for little cost.

PMID- 11957731
TI  - A new approach to organizing philanthropy for a health system. Introducing the
      philanthropy vital signs dashboard.

PMID- 11957732
TI  - The nursing imperative: can fund raising help overcome the nursing shortage?

PMID- 11957734
TI  - Moving towards new horizons.

PMID- 11957733
TI  - Education for health providers in the prevention of the transmission of hepatitis
      C virus: a case study in rural Egypt.

PMID- 11957735
TI  - CD-ROMS available to help facilitate health promotion and education.

PMID- 11957736
TI  - Should school health educators be regarded as professionals and what professional
      knowledge and skills should they possess: the Hong Kong experience.

PMID- 11957737
TI  - A profile of HIV/AIDS epidemic in the African-American community: implications
      for a culturally-sensitive and ethnic-specific health promotion and education
      programme for African-Americans.

PMID- 11957738
TI  - [Ambulance transport of patients with respiratory problems: a prospective
      observational study].
AB  - The aim of this study was to prospectively compile and analyze all emergency
      transports of patients with respiratory problems. The main target variables were
      frequency of the different reasons for transport and treatments administered
      during the emergency event. Special emphasis was placed on the use of inhalation
      therapy. The data of all patients who, in 2000, were transported by the "Realu"
      emergency medical service of the Chur Rhine Valley (a community with a population
      of approximately 100,000) due to respiratory problems were prospectively compiled
      according to predefined criteria. The emergency records and the medical release
      reports were evaluated. A total of 137 patients were prospectively included for
      the year 2000, corresponding to 8% of all patients transported by "Realu" (out of
      a total of 1675 patients). The average age was 66 years (2-98 years). Around one
      fifth of the transports involved patients with exacerbations of chronic
      obstructive pulmonary disease (COPD), pulmonary embolisms, pulmonary infections
      or cardiac dyspnea. Six patients (5%) were transported by ambulance because of
      bronchial asthma. Inhalation therapy was administered in only 41% of the cases
      with obstructive pulmonary disease in which it would have been indicated. In
      conclusion, our evidence shows that bronchial asthma is the primary diagnosis in
      only 6% of the patients requiring emergency transport due to respiratory
      symptoms. In these emergency situations, antiobstructive inhalation therapy was
      given to a mere 41% of the patients suffering exacerbations of COPD or bronchial
      asthma. More frequent use of such a simple and effective treatment should be
      encouraged.

PMID- 11957739
TI  - [Diagnosis of allergic rhinitis].
AB  - Allergic diseases remains an important problem that affects people of all ages.
      The prevalence of allergic rhinitis amounts to 10 to 16% in Central Europe with a
      tendency to be on the rise. Allergic rhinitis constitutes one of the commonest
      causes for visits to a general practitioner. Correct diagnosis is important for
      optimal management. A thorough history should be taken, followed by general and
      endoscopic examinations and confirmatory investigations. Careful examination
      should reveal obvious alternative causes of symptoms, such as polyps or tumours.
      If allergy is suspected, this can be confirmed by further tests, particularly the
      skin-prick test, measurements of serum specific IgE, the nasal provocation test
      of allergens or zytological examination.

PMID- 11957740
TI  - [Diagnosis and treatment of delirium].
AB  - Delirium is a common psychiatric complication in somatically ill in-patients and
      is associated with increased morbidity and mortality, longer lengths of stay and
      higher cost of treatment. It remains often unrecognized and thus inadequately
      treated. The main risk factors, differential diagnosis, primary and secondary
      prevention, non-pharmacological interventions and pharmacological treatment are
      discussed. For the treatment of the non alcohol associated delirium, haloperidol
      remains the treatment of choice, whereas for the treatment of delirium related to
      alcohol withdrawal benzodiazepines and clomethiazole are recommended. Other
      treatment strategies, especially the use of newer atypical antipsychotic
      medications are outlined.

PMID- 11957741
TI  - [What is hiding behind a raised potassium level?].

PMID- 11957742
TI  - [Erythema nodosum and rheumatic fever].

PMID- 11957743
TI  - Pulmonary disposition of budesonide from liposomal dry powder inhaler.
AB  - The Purpose of this study was to establish the use of a developed dry powder
      inhaler of budesonide liposomes in pulmonary drug delivery. Budesonide liposomes
      composed of egg phosphatidyl choline (EPC) and cholesterol were prepared using a
      lipid-film hydration technique. The liposomal dispersion was freeze dried and
      formulated to a dry powder inhaler. The entrapped drug values (91.79% to 78.99%)
      of freeze dried liposomes were estimated in prepared batches after purification
      from the free drug by centrifugation of the rehydrated vesicles. In vitro drug
      retention was evaluated using methanolic phosphate buffer saline and
      bronchoalveolar lavage, following incubation at 37 degrees C. All batches were
      found to retain more than 63.54% of budesonide within liposomes at the end of 24
      h. Rehydrated budesonide liposomes or nonencapsulated budesonide was delivered to
      rat lungs by intratracheal administration. The pulmonary drug disposition was
      assessed by simultaneous monitoring of drug levels in the bronchoalveolar lavage
      and lung tissue. After intratracheal administration, cumulative drug levels in
      the lung tissue indicated that the targeting factor was at least 1.66 times
      higher in liposomes. The maximal drug concentration in the lung homogenate for
      the liposomal dry powder inhaler was 36.64 micrograms as compared to 78.56
      micrograms with the plain drug. Similarly, the time for maximum drug
      concentration in the lung homogenate for the liposomal dry powder inhaler was 9
      12 h as compared to 3 h for that of the plain drug. Hence, the use of a developed
      liposomal budesonide dry powder inhaler was found to provide desired drug levels
      in the lungs for a prolonged period of time, which is expected to enhance the
      therapeutic index of the drug and probably reduce the dose and cost of therapy as
      well.

PMID- 11957744
TI  - Effect of long-term multiple nifedipine administration on the antinociceptive
      activity of acetaminophen.
AB  - The influence of long-term nifedipine administration on the antinociceptive
      activity of acetaminophen on hexobarbital sleeping time and liver monooxygenase
      and synthetase activities was studied in male albino mice. Nifedipine was
      administered orally at a dose of 25 mg/kg daily for 14 and 21 days. The
      nociceptive response was determined by the acetic acid writhing test. There was
      no significant difference in the antinociceptive effect of acetaminophen after
      treatment with nifedipine for 14 days. Nifedipine caused enzyme induction, which
      was demonstrated by shortened hexobarbital sleeping time, enhanced ethylmorphine
      N-demethylase (EMND), aniline-4-hydroxylase (AH), ethoxycoumarine-O-deethylase
      (ECOD), UDP-glucuronyl transferase (UDPGT), glutathione-S-transferase (GST) and
      NADPH-cytochrome c reductase activity and increased content of cytochrome P450
      and cytochrome b5. It is assumed that this effect of nifedipine on acetaminophen
      analgesia is associated with the changes (acceleration) in acetaminophen
      metabolism in the liver after repeated administration of the drug.

PMID- 11957745
TI  - Pharmacokinetic interactions of statins.
AB  - Statins have shown high efficacy in managing hypercholesterolemia in patients
      requiring chronic drug treatment, particularly those who show comorbidity and
      thus receive concomitant medication for other pathologies. According to the
      reported data extensively reviewed in this work, absorption and elimination are
      the kinetic processes mainly affected by this type of interaction, while
      distribution and protein binding is only slightly modified. Products (drugs or
      food) with the ability to affect the activity of protein-mediated transport
      and/or P450 cytochrome systems, particularly the P-glycoprotein and/or CYP3A4,
      respectively, are expected to cause pharmacokinetic interactions with statins.
      The intensity of the interaction is dependent on the statin kinetic profile and
      the capacity of the coadministered product to alter the systems mentioned above.
      Modification of the total HMG-CoA inhibitors instead of just the parent drug
      profile is to be considered when evaluating the clinical relevance of the
      interaction. Interindividual variability must also be taken into account when
      extrapolating results from studies performed in small groups of relatively
      healthy individuals. Patients treated with other drugs that have the potential
      ability to interact with statins should be monitored.

PMID- 11957746
TI  - [The aged person's kidney: renal aging or renal limit mass].

PMID- 11957747
TI  - [3 rare cases of textiloma after renal surgery. Review of the literature].
AB  - OBJECTIVE: To review the literature on textiloma or surgical sponges left during
      renal surgery because of the important medical-legal implications of this
      complication. METHOD: Three cases of textiloma in patients undergoing renal
      surgery are presented. Two of them had undergone surgery at other hospitals 26
      and 4 years earlier. The third patient had undergone transplantation at our
      hospital and was reoperated 4 months later for a purulent cutaneous fistula
      caused by the textiloma. RESULTS/CONCLUSIONS: A review of the literature since
      1950 showed few reports of textiloma. The risk factors according to the type of
      surgery performed and current controls in the operating room to avoid this
      complication that can occasionally be severe, are presented in detail. The forms
      of presentation, diagnostic methods and difficulties encountered due to the long
      period of time the foreign body has been left indwelling, are analyzed. To our
      knowledge, 8 cases of textilomas have been reported in patients undergoing renal
      surgery.

PMID- 11957748
TI  - [Controversies in the evaluation of asymptomatic microhematuria].
AB  - OBJECTIVE: Asymptomatic microhematuria continues to be a problem. It has a
      prevalence of 16% and numerous conditions can present this clinical
      manifestation. METHODS: A prospective study was carried out on all patients that
      consulted at the urological services during 2000 for asymptomatic hematuria.
      Patients presenting with irritative symptoms, urethral secretion, perineal or
      suprapubic pain, urinary tract infections, renal lithiasis or history of trauma
      were not included in the study. RESULTS: None of the patients presented tumors.
      Two patients presented renal lithiasis, 5 simple renal cysts, 8 hypercalciuria
      and 3 hyperuricosuria. None of the 11 patients with hypercalciuria or
      hyperuricosuria had a history of lithiasis. CONCLUSIONS: Although the size of the
      study is small, the incidence of tumors in patients with asymptomatic
      microhematuria appears to be far from the 12.5% incidence reported by some
      authors and might probably be closer to the 0.5% incidence reported by others.
      Furthermore, the significant pathology (renal lithiasis), which requires
      treatment, is also infrequent.

PMID- 11957749
TI  - [Statistical study of probabilities of rectal palpation, total PSA, and PSA
      density in prostate cancer].
AB  - OBJECTIVE: To analyze the probabilities of total PSA, digital rectal examination
      (DRE) and PSA density in prostate cancer diagnosed by ultrasound-guided sextant
      prostate biopsy. METHODS: The clinical records of 170 patients with elevated PSA
      levels and/or symptomatic BPH that had been referred to the outpatient services
      of the urology department were reviewed. Ultrasound-guided sextant prostate
      biopsy was performed in all patients. Serum PSA and PSA density were determined
      before biopsy. Age and DRE findings were also analyzed. RESULTS/CONCLUSIONS:
      Statistical analysis showed a significant difference (p < 0.00001) for DRE, PSA
      and PSA density in relation to the prostate biopsy. Concerning the magnitude of
      the effect of DRE adjusted for age. PSA and PSA density determined by logistic
      regression analysis, a significance was found for DRE (odds ratio: 9.7) and PSA
      density > 0.5 (odds ratio: 11.3). DRE showed a sensitivity of 59%, a specificity
      of 89% and a positive predictive value of 88%.

PMID- 11957751
TI  - ["History of Urology." A new section of the Archivos Espanoles de Urologia].

PMID- 11957750
TI  - [Urinary BTA-TRAK in the follow-up of superficial transitional-cell bladder
      carcinoma].
AB  - OBJECTIVE: To determine the efficacy of urinary BTA-TRAK as a marker in
      monitoring superficial transitional cell carcinoma of the bladder and to compare
      urine cytology with urinary sediment testing. METHODS: 700 consecutive
      determinations using BTA-TRAK to monitor unselected patients that had undergone
      surgery for transitional cell carcinoma of the bladder were analyzed. Cystoscopy,
      urinary sediment and urine cytology were performed during follow-up. Urography
      was performed yearly or when tumor of the upper urinary tract was suspected.
      (positive cytology or hematuria with no bladder tumor). Cystoscopy was performed
      a few days after determination of BTA-TRAK and voiding urine cytology and urinary
      sediment analyses (considered positive when microhematuria was observed) were
      both requested. RESULTS: Of the 700 determinations, 95 (13.6%) were urothelial
      carcinomas (93 bladder, 2 upper urinary tract) that had been discovered during
      patient monitoring. Of the 93 bladder tumors, 39 were Ta (37 TaG1 and 2 TaG2), 29
      T1 (4 T1G1, 20 T1G2 and 5 T1G3), 5 Tis and 20 muscle-infiltrating tumors
      (progression from T2-4 during monitoring). The sensitivity of urine cytology to
      detect urothelial tumor was 41.1% and the specificity was 97.3%. The urine
      cytologies were negative in 48.4% and inflammatory in 9.5% of the tumors. The
      sensitivity was 19% in low grade tumors. The sensitivity of urinary sedimentation
      testing to detect urothelial tumor (microhematuria) was 40% and the specificity
      was 96.7%. When associated with pyuria, it was considered to be a urinary
      infection or urothelial inflammatory condition, which was observed in 10.6% of
      the cases. Considering the proposed normal reference value for BTA-TRAK (< or =
      14 U/ml), we have found a sensitivity of 62.1% and a specificity of 68.4%. A
      logistic regression model was developed, including BTA-TRAK, urinary
      sedimentation and cytology, to identify the independent variables that are useful
      for tumor detection during follow-up of superficial carcinoma of the bladder in
      this series. The combination of three variables showed an odds ratio of 18.5 (8.9
      38.5) for urinary cytology, 11.8 (5.9-23.5) for urinary sedimentation and an odds
      ratio for BTA-TRAK that did not fall within the equation. CONCLUSIONS: Although
      overall the sensitivity of BTA-TRAK is higher than that of urine cytology and
      urinary sedimentation testing, it provides no additional information than that
      obtained from the combination of urine cytology and urinary sedimentation testing
      in the detection of tumor recurrence during monitoring for superficial bladder
      cancer.

PMID- 11957752
TI  - [Radical cystectomy for superficial tumors in the BCG era].
AB  - OBJECTIVE: To analyze the indications and outcome of cystectomy for superficial
      bladder cancer since the introduction of BCG therapy. METHODS: From June 1990 to
      December 1996, 384 patients underwent cystectomy for transitional cell bladder
      tumor. A retrospective study was carried out on 43 cases (11.1%) that underwent
      cystectomy for Tis, Ta, T1 tumors. The characteristics of patients with
      superficial bladder cancer, correlation between the clinical stage (determined
      after TUR) and pathological findings (cystectomy specimen) and outcome were
      analyzed. RESULTS: 36 patients were male and 7 were female; mean age 63 years
      (range 39-79). Mean follow-up was 48 months (8-120). Twenty-nine patients
      received BCG therapy prior to surgery. No response to BCG was the main indication
      for cystectomy. By clinical stage, 79% were high grade, 65% T1 and 65% CIS. A
      correlation between the clinical stage and the pathological findings was found in
      32.5%, overstaging in 28% and understaging in 39.5%. The increase in stage after
      analysis of the surgical specimen in 13 patients (30%) was due to progression of
      the superficial bladder tumor to infiltrating or metastatic tumor. Urinary tract
      tumor was found during follow-up in 8 patients (18.6%). Eleven patients died of
      bladder cancer, 3 of other causes and 29 (67%) are free of disease. Seven of the
      13 patients (53%) that were clinically understaged and had infiltrating tumor or
      metastasis died. CONCLUSIONS: No response to BCG therapy was the main indication
      for cystectomy. Before starting conservative treatment for high risk superficial
      bladder cancer, the possibility of endoscopic understaging should be taken into
      account. Patients undergoing cystectomy for superficial bladder cancer have a
      high risk of developing urinary tract tumor.

PMID- 11957753
TI  - [Erectile function after myocardial revascularization surgery. Analysis of 30
      cases].
AB  - OBJECTIVE: To assess prospectively the impact of extracorporeal circulation on
      erectile function and the probable prognosis of future erectile function in
      patients undergoing myocardial revascularization surgery. METHODS: 30 patients
      who met the following criteria were analyzed: a) age less than 80 years, b)
      elective surgery, c) use of extracorporeal circulation and d) stable partner. Pre
      operative erectile function was determined and other cardiovascular risk factors
      by means of a written questionnaire. The patients were classified into three
      groups according to the preoperative erectile function: good (group A), fair
      (group B) and poor (group C). All patients underwent myocardial revascularization
      surgery. RESULTS: 3 patients (27.2%) of group A reported poor erections after
      surgery, while 8 (72.7%) reported no changes in erectile function. Four patients
      (44.4%) of group B reported poor erection postoperatively, another 4 (44.4%)
      reported no significant changes in erectile function and 1 (11.1%) reported
      improvement in erectile function. One patient (10%) of group C reported improved
      erectile function, while the remaining patients reported no changes. To determine
      the influence of extracorporeal circulation and clamping time on erectile
      function as independent variables, the patients were classified into group I
      (patients of groups A and B that preserved or improved erectile function
      postoperatively) and group II (patients of groups A and B that reported poor
      erectile function postoperatively). The mean extracorporeal circulation time was
      99 mins for group I and 116 mins for group II (p = 0.7102). The mean clamping
      time for group I was 56.84 mins and 69.57 mins for group II (p = 0.5375). No
      statistically significant differences were found (Wilcoxon test). CONCLUSIONS: A)
      Patients with good erectile function undergoing myocardial revascularization
      surgery with extracorporeal circulation have a high probability of preserving the
      quality of erectile function postoperatively. B) Patients with erectile
      dysfunction are not likely to improve after myocardial revascularization surgery.
      C) Extracorporeal circulation and clamping times do not appear to influence the
      postoperative results. These were significantly shorter in patients that
      preserved or improved erectile function than in those that reported poor erectile
      function postoperatively and may be due to less intraoperative complexity. D) The
      preoperative erectile function was found to be the most important predictive
      factor of outcome. E) Further studies on larger series of patients are warranted
      to corroborate the foregoing findings.

PMID- 11957754
TI  - [Prostaglandin treatment in neurological patients with erectile dysfunction].
AB  - OBJECTIVE: To evaluate the efficacy of prostaglandin E1 in the treatment of
      erectile dysfunction in patients with spinal cord or head injury. METHODS: The
      study comprised 41 patients; 5 head and 36 spinal cord injury. Of these 36
      patients, 20 had a lesion in the dorsal and 26 in the lumbosacral spine; 11 were
      complete and 25 incomplete. Mean age was 38.5 years. Therapy was started at a
      minimum dose of 5 mg up to maximum of 20 mg in each patient. All patients were
      taught the correct use of intracavernous self injection of prostaglandin E1. The
      analyses, ECG and penile echo Doppler evaluations of all patients showed no
      significant findings that contraindicated treatment. The overall response and the
      response according to the site of lesion, type of lesion and age were evaluated.
      RESULTS: The overall response rate was 78.8%. Erection was not achieved in 9
      patients even with the 20 mg maximum dose. The response rate was 100% in the
      group of patients with head injury. In the spinal cord injured patients, the
      response rate was 83.3% in patients < 30 years and 57.2% in patients > 30 years
      old. The 2 mg dose was effective in 1 patient, the 10 mg in 17 and the 20 mg dose
      in 14 patients. A positive response was achieved in 55.5% of the patients with
      complete and 72.7% of the patients with incomplete spinal lesions. No
      complications of intracavernous injection of prostaglandin were found.
      Prostaglandin self injection therapy achieved satisfactory results in all
      patients. CONCLUSIONS: Prostaglandin injection is very effective in the treatment
      of erectile dysfunction in patients with spinal cord or head injury. A higher
      percentage of efficacy was found in the younger patients, in those with
      incomplete lesions and those with head injury. The dose required is usually lower
      than in the non neurological patients.

PMID- 11957755
TI  - [Distal bone metastases of transitional-cell carcinoma of the bladder. Apropos of
      a case].
AB  - OBJECTIVE: To report a case of transitional cell carcinoma of the bladder
      metastatic to the right knee and review the literature. METHODS/RESULTS: A 65
      year-old patient who had refused to undergo surgery for a T2 N0 M0 bladder tumor
      in 1995 was admitted for poor general condition and a mass in the right knee.
      Biopsy confirmed bony metastasis of a carcinoma compatible with primary
      urothelial tumor of the bladder. CONCLUSIONS: Bony metastasis of transitional
      cell carcinoma of the bladder is relatively frequent and mainly to the spine.
      Distal bony lesions are rare and usually appear in the advanced stages of the
      disease.

PMID- 11957756
TI  - [Acute scrotum secondary to testicular tumor].
AB  - OBJECTIVE: To report a case of testicular tumor, classified as seminoma, with a
      very uncommon form of presentation since it presented as acute scrotum. METHODS:
      The clinical features, treatment and outcome of this uncommon condition are
      presented. RESULTS: A review of the literature showed that this form of
      presentation is rare although in the present case it is impossible to determine
      if testicular inflammation was due to tumor necrosis or infection from the
      associated hydrocele. CONCLUSIONS: Testicular tumor should be considered in all
      male patients aged 20 to 35 years with acute scrotum.

PMID- 11957757
TI  - [Mesothelial cysts in urology: a diagnostic and therapeutic problem].
AB  - OBJECTIVE: To present our experience with mesothelial cysts with excretory system
      involvement. METHODS: 3 cases of mesothelial cyst are presented; two of them
      caused obstructive uropathy. RESULTS: Cases 1 and 2 were treated by surgery,
      while case 3 was managed conservatively. All cases are currently asymptomatic.
      CONCLUSIONS: Mesothelial cysts are an uncommon cause of obstructive uropathy.
      Treatment is by surgery for the symptomatic cases and conservative management is
      a valid alternative for the asymptomatic cases.

PMID- 11957758
TI  - [Stage II focal xanthogranulomatous pyelonephritis].
AB  - OBJECTIVE: To report a case of focalized stage II xanthogranulomatous
      pyelonephritis and the diagnostic difficulties encountered. METHODS: A 63-year
      old female consulted at the emergency services for fever during the last two
      months and right lumbar pain. Urinary cultures were negative. A CT scan showed a
      poorly-defined heterogeneous mass in the lower pole of the right kidney. Fine
      needle punction-aspiration biopsy was compatible with renal cell carcinoma. The
      patient underwent radical nephrectomy. RESULTS: The histopathological study
      showed focalized stage II xanthogranulomatous pyelonephritis but no evidence of
      neoplasia. CONCLUSIONS: Xanthogranulomatous pyelonephritis can mimic the
      clinical, cytological and imaging features of renal neoplasia.

PMID- 11957759
TI  - [Bladder leiomyoma: diagnosis by imaging].
AB  - OBJECTIVE: To report a case of leiomyoma of the bladder in a patient with
      unspecific urinary symptoms and discuss the utility of the diagnostic imaging
      techniques. METHODS/RESULTS: A 56-year-old woman who consulted for unspecific
      urinary symptoms is described. Patient evaluation with ultrasound, CT and MRI
      showed a mass in the posterior aspect of the urinary bladder. CONCLUSIONS:
      Leiomyoma of the bladder is an uncommon benign tumor that is asymptomatic in most
      of the cases and is frequently discovered incidentally during assessment for
      other conditions. The case described herein presented with unspecific urinary
      symptoms. Patient evaluation with different diagnostic imaging techniques was
      required for correct diagnosis and treatment.

PMID- 11957760
TI  - [Aggressive fibromatosis of the penis (desmoid tumor)].
AB  - OBJECTIVE: To describe an additional case of desmoid tumor of the penis. The
      incidence, etiopathogenesis, symptoms, diagnosis and treatment of this condition
      are discussed. METHODS: A 70-year-old male consulted at the emergency services
      for pain and urinary symptoms. Physical examination showed no regional
      lymphadenopathy. Patient assessment by ultrasound and CT disclosed a penile
      lesion. Treatment was by wide local excision. RESULTS: Control evaluation at 3, 6
      and 12 months showed normal findings and the patient remains asymptomatic.
      CONCLUSIONS: Wide local excision is advocated as the treatment of choice for
      desmoid tumor of the penis.

PMID- 11957761
TI  - [Plasma-cell granuloma of the kidney pelvis].
AB  - OBJECTIVE: To report a rare case of plasma cell granuloma of the renal pelvis. To
      our knowledge, only five cases have been reported in the literature. METHODS:
      Clinicopathological description of a case of plasma cell granuloma of the renal
      pelvis with light chain immunohistochemical study. RESULTS: A young male patient
      with a radiologically benign mass in the right renal pelvis extending into the
      upper calices that caused hematuria is described. The diagnosis was suggested
      during the intraoperative study of the mass that was suggested by pyelotomy
      (conservative surgery). Immunohistochemical study confirmed the initial
      diagnosis. CONCLUSIONS: Although this condition is rare, plasma cell granuloma,
      an inflammatory pseudotumor, can occur in the urinary tract and should be
      considered in the differential diagnosis of mass lesions. Histopathological
      diagnosis requires a complete study of the entire tumor and the use of
      immunohistochemical techniques to discard plasmacytic non-Hodgkin lymphoma or
      neoplastic plasma cell proliferation.

PMID- 11957762
TI  - [Leonardo de la Pena Diaz (1875-1957) and the founding of the first chair of
      urology in Spain].
AB  - OBJECTIVE: The creation of the first chair of Urology in Spain and, consequently,
      the official recognition of the specialty in the urinary tract as a subject in
      the university curriculum was not an easy task for the urologists early in the
      last century. The curriculum of 1886 and 1902 included some medical specialties
      in the licentiate (ORL, Ophthalmology, Dermatology and Venereal Disease, and
      Neuropathy) as complementary and subsequently compulsory subjects, but not
      Urology. Perhaps this was due to the lack of representative or influential
      urologists that could exert pressure on the ministers of Public Education at that
      time. Although the Spanish Society of Urology was founded in 1911 and some
      urologists like Rafael Molla and Rodrigo and Leonardo de la Pena Diaz, professors
      of the Central University, exerted pressure on the university faculty, Royal
      Academy of Medicine and the Ministry of Public Education, Urology was not
      included in the curriculum until 1920, although, in my view, its category was
      again devaluated since it was only an optional subject in the licentiate or
      doctorate. Apart from the procedures and processes, convoking the chair required
      political and administrative maneuvers that are shown in a broad review of
      newspaper articles and documents of that period. The controversial result of the
      competition based on merits that some considered should have been competition for
      a position according to the convocation, is no discredit to Leonardo de la Pena
      Diaz (1875-1957), the first professor of Urology in the history of Spanish
      Medicine. An unbiased historical and discerning evaluation clearly shows that his
      merits, accomplishments, tenacity and competence in teaching made him the most
      appropriate for the position. His merits were finally recognized not only by the
      board but also by his opponents.

PMID- 11957763
TI  - Tamsulosin: effect on quality of life in 2740 patients with lower urinary tract
      symptoms managed in real-life practice in Spain.
AB  - OBJECTIVE: To investigate the influence of tamsulosin treatment on the severity
      of lower urinary tract symptoms (LUTS) and the impact on quality of life (QoL),
      including daily life activities and mental well being, in real life practice in
      Spain. METHODS: 2740 LUTS patients aged 45-75 years who visited a urologist
      office in Spain received tamsulosin 0.4 mg o.d.. At baseline, after 3 months and
      after 6 months of treatment a questionnaire was completed by the urologist and
      the patient. The urologist estimated some aspects of the patient's QoL related to
      his LUTS. The International Prostate Symptom Score (I-PSS) was used to assess the
      severity of LUTS, while the BPH-Specific Interference with Activities (BSIA) and
      the Total Mental Health Rate assessed the impact on daily life activities and
      psychological well being respectively. RESULTS: After 3 months of treatment
      tamsulosin significantly improved the mean total I-PSS compared to baseline.
      After 6 months, the mean total I-PSS was reduced by 11.0 points from a baseline
      score of 20.3 (> 50% reduction). Tamsulosin also significantly improved the mean
      total BSIA score and the mean Total Mental Health Rate. These observations were
      confirmed by the urologists' assessment of the patient's condition: an increase
      of more than 50% of patients with no or mild voiding and filling LUTS and an
      increase of 45% of patients with no or only a small interference of their LUTS
      with daily life activities. The withdrawal rate due to adverse reactions was
      2.4%. CONCLUSION: This study shows that tamsulosin improves LUTS and their impact
      on the patient's QoL and daily life activities, in the opinion of both the
      patients and the urologists.

PMID- 11957764
TI  - Esophageal perforation in the premature newborn: case report and review of the
      literature.
AB  - We report a case of esophageal perforation in a premature infant probably related
      to instrumentation. The child had also received the nonsteroidal anti
      inflammatory drug, indomethacin. An exhaustive review of the literature has been
      done to define the clinical profile and current recommendations for management.

PMID- 11957765
TI  - Effect of gender on outcome following infrainguinal bypass graft surgery: a
      systematic review.

PMID- 11957766
TI  - Drotrecogin alfa (activated) for severe sepsis.

PMID- 11957767
TI  - Medical liability and CMIC.

PMID- 11957768
TI  - The Connecticut Partnership Program for long-term care.

PMID- 11957769
TI  - Customer service vs patient care.
AB  - Though hospital administrators may impose a customer satisfaction mandate, it
      need not alter the status of "patients" redefined as "customers." It is the duty
      of all health care providers to remember that the practice of medicine is not
      chiefly a business and is not purely a science. In its mission is the art of
      encouraging the individuality of each provider of medical care to interact with
      the individuality of his/her patients. The medical profession in antiquity was
      linked with religion and the treating physician with special acquired knowledge
      and clinical experience was often able to accomplish a "miracle" when TLC (tender
      loving care) was the essential element of medical practice. If TLC is
      reintroduced into 21st century medical practice, "customer satisfaction" will be
      the result rather than the goal of medical care.

PMID- 11957770
TI  - Science and risk.

PMID- 11957771
TI  - Mental health parity. Why not? Why not!

PMID- 11957772
TI  - OSHA--is your practice in compliance?

PMID- 11957773
TI  - The phenomenon of compulsive buying.

PMID- 11957774
TI  - Medicine's interdisciplinary quilt.

PMID- 11957776
TI  - [Naturo-economic aspects of ecologic agriculture strategy].
AB  - The most important problems related in agricultural production both in quality
      and value terms are their natural and market conditions, changes in food
      processing industry and in foreign trade. Opportunities for food production
      development and outlook for changing demand for food have been considered.

PMID- 11957775
TI  - [Ecotoxicology, human ecology, laser biotechnology in primary prevention of
      environmental health hazards].
AB  - Interdisciplinary studies in ecotoxicology (including the influence of complex
      physical, chemical and biological factors on ecosystems and human food chain),
      human ecology (related to estimation of individuals exposition to different
      pollutants both in the natural environment and in-door environment, as well as by
      food) and environmental biotechnology (based on application of high sensitive
      biological, especially embryological criteria in biotests for water quality,
      including image computisation and biosensors)--are scientific base for primary
      prevention of disturbances of the ecological balance as well as environmental
      risk factors for human health. Large scale applications of laser biostimulation
      in environmental engineering is a new chance for system approach in primary
      prevention by more efficient nutritional prevention, protection of proper water
      quality (including biotests) and protection of the human environment in working
      and living places.

PMID- 11957777
TI  - [Determination of content of zinc and cooper in table and therapeutic mineral
      water].
AB  - Mineral table water and therapeutic water are good sources of macro- and
      microelement. Increase of consumption and variety of kinds of mineral water was
      the reason for undertaking this research. Contents of zinc and copper were
      determined in 13 kinds of mineral table water and in 12 kinds of therapeutic
      water by Atomic Absorption Spectrometry method (AAS) in Pye-Unicam SP0192
      apparatus, after earlier concentration. Content of copper in mineral table water
      was from 0.4 microgram/l in "Krynica Zdroj" water to 11 micrograms/l in
      "Mazowszanka" water and in therapeutic water and from 1.7 micrograms/l to 22.6
      micrograms/l. Content of zinc in mineral table water was from 7 micrograms/l to
      640 micrograms/l and in therapeutic water was from 24 micrograms/l to 88
      micrograms/l.

PMID- 11957778
TI  - [The metal concentration in water and ground deposit in the area of Upper
      Silesia].
AB  - The metal concentration in water and ground deposits of 6 collapse water
      reservoirs in the area of Upper Silesia was tested. The examined reservoirs are
      situated in the so-called cross-town tract near Swietochlowice and Ruda Slaska.
      It was concluded that the metal concentration in water samples was low. In
      accordance with the present regulations, this allows to classify the water in
      these reservoirs to the 1st class purity water. The metal content in the ground
      deposits is high. Iron (Fe) concentration in the deposits ranged from 28288.9
      mg/kg to 39162.9 mg/kg; the concentration of manganese (Mn) ranged from 2557.95
      mg/kg to 3398.52 mg/kg and that of zinc (Zn) was 1288.78 mg/kg average through
      the year. The highest zinc concentration reached 2834.74 mg/kg. Cadmium (Cd)
      occurred in the deposits in the content of 10.4 mg/kg. The average year
      concentration of lead (Pb) in the deposits was 252.4 mg/kg. Copper (Cu) was found
      in the deposits in the amount of 45.0 mg/kg. The highest concentration of this
      metal in the ground deposits was 103.14 mg/kg. Magnesium (Mg) was on average
      present in the deposits in the concentration of 1913 mg/kg and its highest
      concentration reached 6777.89 mg/kg.

PMID- 11957779
TI  - [The level of nitrates in drinking water of selected water wells situated in the
      parish of Szydlowiec].
AB  - In the last decades it has been found out that elevated levels of nitrates in
      drinking water and eatable plants have the negative impact on human health.
      During transportation, keeping and preparing the vegetables for consumption, as
      well as in the human body itself, nitrates undergo the reduction into nitrites
      (nitrate(III)). This reduction process runs relatively fast in the alimentary
      canal of infants under the age of 6 months. Nitrites, in the presence of some
      substances that occur in foodstuff, can favour the cancerogenic processes. In
      addition to that, nitrites can lead among infants to the disease called
      methemoglobinemia (blue baby syndrome). In 1986 WHO fixed the limit of the
      contents of nitrates in drinking water to 10 mg N-NO3-/dm3 (45 mg NO3-/dm3). The
      aim of this study was to evaluate the level of nitrates in the water of selected
      drinking water wells situated in the parish of Szydlowiec, a province of
      Swietokrzyskie. The study was conducted in three series, i.e.: in the summer of
      1995, in the winter of 1996 and in the summer of 2001. The concentration of NO3-
      in water was determined (in situ) with the Merckoquant Nitrate test kits of the
      Merck Company. The obtained results show that the NO3- concentration in the water
      of the majority of studied wells exceeds clearly the acceptable NO3- drinking
      water standard established for drinking water by WHO.

PMID- 11957781
TI  - [The results of ten year activity of the Environmental Health Outpatient
      Department in Piekary Slaskie in the prophylaxis of lead intoxication in
      children].
AB  - Aim of the study is the prophylaxis in children exposed to environmental lead.
      The analysis of lead concentration in blood as the result of the effectiveness of
      pharmacological and climatic-rehabilitating treatment was shown. Data were
      collected in the Environmental Health Outpatient Department in Piekary Slaskie,
      which was created in 1991 as an effect of pro-ecological activity in the town.
      The 6219 children in years 1986-2001 were examined. 2700 of children were sent
      for the propylactic-therapeutic camps. Ten years activity of the Environmental
      Health Outpatient Department in Piekary Slaskie contributed to lowering of
      percentage of children with lead concentrations in blood over 10.0 micrograms/dl
      of 28.4% in 1992 to about 19% in 2000. This activity together with organizing the
      prophylactic-therapeutic camps by the Silesian Children's Help Association
      'Bratek' considerably allowed to limit the exposure of children population to
      environmental lead in Piekary Slaskie.

PMID- 11957780
TI  - [Influence of thermal processing and storage on the content of nitrates and
      nitrites in chosen vegetables from the Podlasie province].
AB  - The dangerous for health nitrate and nitrite can penetrate with food human
      organism for this reason in study the influence of thermal processing and storage
      on the level of these compounds in the vegetables was determined. The content of
      nitrates and nitrites was determined in such vegetables as carrot, parsley-root,
      celery and potatoes growing by farmers in the Podlasie province. Nitrates and
      nitrites were assessed in fresh and boiled vegetables as well as in the stock and
      in carrot juice. These compounds were also determined after storage of vegetables
      at +4 degrees C for 2 weeks and at -15 degrees C for 1 and 3 months. Nitrates and
      nitrites concentrations were assayed colorimetrically by the Griess method
      modified to food investigation. Boiling reduced nitrate content in the
      vegetables. Considerable part (about 50%) of these compounds passed into stock
      during boiling. Storage of these vegetables at +4 degrees C resulted in slight
      lowering of nitrate content in carrot and parsley-root and marked elevation in
      celery. Cold storage of vegetables through 1 and 3 months had no important
      influence on nitrate content. Boiling decreased the content of nitrites similarly
      as nitrates. Storage of the vegetables at +4 degrees C through 2 weeks led to an
      increase in nitrite content in carrot and parsley-root while in celery the
      content of nitrites was reduced. Storage of vegetables at -15 degrees C resulted
      in lowering content of nitrite. The study revealed that the vegetable-roots
      (carrot, parsley and celery) and potatoes cultivated in the Podlasie province as
      well as in the other provinces were excessively contaminated by nitrates and
      nitrites. Moreover, it has been shown that thermal processing such as boiling
      considerably reduced the content of nitrates and nitrites in these vegetables
      while freezing changed mainly nitrite content.

PMID- 11957782
TI  - [Cadmium and lead content in some herbs, herbal preparation and herbal infusions
      used by children and adults].
AB  - The object of the study were some herbs and preparations of herbs used by
      children and adults from Lublin's drug-stores and herbal-stores in 2001. The
      samples of herbs, preparations of herbs and their infusions after evaporation
      were mineralized in "dry" method in the temp. of 450 degrees C. Cadmium and lead
      contents were estimated by AAS method from the organic phase. In preparations for
      children, 56% of the examined samples contained Cd amounts exceeding accepted
      limits. Levels of Pb were innormal. In herbs and herbal preparations for adults
      the norm was exceeded in 70% of samples for Cd and 42% for Pb.

PMID- 11957783
TI  - [Environmental exposure of the Wroclaw inhabitants to nickel and assessment of
      its nephrotoxic effects].
AB  - The aim of the research was to evaluate the environmental exposure of Wroclaw
      inhabitants on nickel compounds and an assessment of their nephrotoxic effects.
      The study was realized in a group of 74 inhabitants of the Wroclaw's district
      Krzyki and compared with a group of 24 inhabitants of the countryfield Kobierzyce
      community located in the 20 km distance from Wroclaw. A nickel concentration was
      measured in morning urine of all the Wroclaw inhabitants, whereas nephrotoxicity
      indices were determined in the 26 inhabitants characterised by the increased
      nickel concentration (2.8 micrograms/l); in urine of 19 inhabitants this
      concentration was found to be normal. The average nickel concentration in the
      urine of the 74 Wroclaw inhabitants was equal to 2.85 +/- 0.22 micrograms/l.
      40.5% of this group were characterised by the concentration higher than the
      physiological one, 4.05% of this group had that concentration higher than 7.9
      micrograms/l which gives an evidence of the environmental exposure. In the
      Kobierzyce group the average nickel concentration in urine was 3.34 +/- 0.23
      micrograms/l which is significantly higher (at p < or = 0.001) than that for the
      Wroclaw group. Moreover, in the Kobierzyce group, 62.5% inhabitants was higher
      the nickel concentration than the physiological one but still lower than the
      environmental exposure. Our results indicate that the Wroclaw inhabitants are not
      more exposed to nickel compounds in comparison with the countryside inhabitants.
      A nephrotoxic action of nickel was detected through the increased excretion of
      the sialic acid in urine which is an evidence of the reduced glomelural
      filtration. A positive correlation between the urine nickel concentration and the
      urine free sialic acid was found (r = 0.61). No increase in the urine N-acetyl
      beta-D-glucosaminidase (NAG), isoenzyme NAG-B, beta 2-microglobulin (beta 2 M)
      and retinal binding protein (RBP) concentrations were found which could indicate
      a damage in kidney tubules.

PMID- 11957784
TI  - [Serum immunoglobulin E concentration in workers producing chlorfenvinphos].
AB  - Organophosphorous pesticides exert sensitizing effects. Our investigations in
      workers of the chlorfenvinphos production department showed frequent incidence of
      the upper respiratory tract allergy as well as diminished specific airways
      conductance. The aim of the study is to assess serum immunoglobulin E
      concentration in the workers of the chemical plant department producing
      chlorfenvinphos. The study covered the entire staff of the department:--35 men
      aged 25-55 years, employed for 1-15 years. Chronic bronchitis was diagnosed in 13
      (37.1%) workers; in none of the subjects examined bronchial asthma was found.
      Spirometry showed a lower Tiffeneau's index in 5 (14.3%) and impaired specific
      airways conductance in 11 (31.4%) workers. Air chlorfenvinphos concentration in
      the work environment did not exceed MAC level, the average concentration was
      0.0008-0.0018 mg/m3, and the erythrocyte acetylcholinesterase activity was within
      normal range. Serum IgE concentration was evaluated with the enzyme immunoassay
      (Enzymun-Test IgE from Boehringer, Cat. No. 1289071), the results were compared
      with those of a control group of 30 healthy male inhabitants of the region,
      professionally not exposed to chemical noxes. Mean serum IgE concentration in the
      workers (109.6 +/- 120.0 IU/ml) was significantly (p < 0.01) higher as compared
      to the control group (51.1 +/- 36.4 IU/ml). In 14 (40.0%) workers the IgE
      concentration exceeded 100 IU/ml, whereas in the control group only in 4 (13.3%)
      people the IgE level was elevated. The results of our investigations provide
      support for an essential role of type I hypersensitivity reaction in the
      pathogenesis of inflammatory changes in the respiratory system caused by
      chlorfenvinphos.

PMID- 11957785
TI  - [Drinking water quality standards and methods of its enforcement in Poland].
AB  - In the paper quality requirements towards drinking water according to the
      Directive of the European Community and according to the Polish rules currently
      in force were compared. It was pointed at excessive enlargement of the Polish
      regulations in the field of physico-chemical index norming as well as objective
      difficulties in executing of these regulations, caused by lack of adequate
      methods of analytical control. Necessity of requirement rationalization within
      the novelization being carried out now was also emphasized.

PMID- 11957786
TI  - [Laboratory diagnosis of herpes zoster: virology or serology?].
AB  - BACKGROUND: The diagnosis of herpes zoster is mostly based on clinical findings.
      In atypical cases, rapid and reliable virological diagnostics is necessary
      because effective antiviral chemotherapy is available. PATIENTS AND METHODS: The
      meaningfulness and practicability of conventional diagnostic methods mostly used
      such as antigen staining, virus isolation and detection of virus-specific
      antibodies were compared with polymerase chain reaction (PCR) in 100 patients
      with zoster. RESULTS: PCR using oligonucleotides selected from the open reading
      frames 28 and 29 of the varicella-zoster virus (VZV) genome showed the highest
      sensitivity of 94% and a specificity of 100%. Direct immunofluorescent antigen
      staining carried out within few hours had a sensitivity of 82% and a specificity
      of 70%. However, results could only be obtained in 71% of the cases. On the basis
      of serologic parameters, an active VZV infection was detected in 61% of the
      patients. Virus culture frequently regarded as "gold standard" was successful in
      20%. There was a strong dependence on the time of collecting specimens and the
      immunocompetence of the patients. CONCLUSIONS: The study shows that the PCR has
      to be considered the method of choice for the diagnostics of zoster with an
      atypical course. Serological methods can only be recommended to confirm the
      diagnosis retrospectively.

PMID- 11957787
TI  - [Measurement of outpatient treatment costs of chronic inflammatory bowel diseases
      at a German university hospital].
AB  - OBJECTIVE: To create a concept for measuring and valuating resource utilization
      of outpatient treatment of patients with inflammatory bowel disease in a German
      university hospital. MATERIAL AND METHODS: The measurement of health services was
      achieved using a computer-based routinely administered data base of the Medical
      Department. Measuring costs was performed in three steps: 1. identification of
      the categories of resource utilization, 2. quantitative measurement of resource
      use, 3. monetary valuation of the utilization of resources using German fee
      schedules and prices for drugs. RESULTS: The resource utilization of 272 patients
      with a treatment period of more than 1 year could be identified in a structured
      form. Categories of resource use could be identified and quantitatively measured
      as follows: anamnesis and physical examination by a physician in 100% of the
      visits, laboratory tests in 87.1%, endoscopic or sonographic services in 36.9%,
      and radiologic procedures in 14.1%. In 93.6% of the visits a medication was
      prescribed. Annual costs of outpatient care provided by the hospital were 3,171
      [symbol: see text] per patient. Medication accounted for 85% of total costs.
      Analyzing the costs of medical treatment, mesalazine was the major cost component
      (48%), followed by budesonide (15%). CONCLUSION: The presented concept offers a
      good access to measure costs of outpatient treatment of patients with
      inflammatory bowel disease. It is suitable for measuring costs in the economic
      evaluation of alternative treatments or diagnostic strategies in an outpatient
      setting. It furthermore may be used as a component in cost-of-illness studies.
      For transferring the concept to other hospitals, the availability of a routine
      documentation of services should be checked. For economic analysis, a further
      data management is required.

PMID- 11957788
TI  - [Current status of lung transplantation: patients, indications, techniques and
      outcome].
AB  - BACKGROUND: Lung transplantation has evolved to a standard treatment modality for
      patients suffering from end-stage lung diseases. INDICATIONS: Accepted
      indications for lung transplantation include chronic obstructive pulmonary
      disease of the lung (COPD) and other causes of emphysema (i.e., alpha-1
      antitrypsin deficiency), parenchymal diseases (i.e., idiopathic pulmonary
      fibrosis), genetic disorders such as cystic fibrosis, vascular diseases (i.e.,
      primary pulmonary hypertension), chronic infectious diseases (i.e.,
      bronchiectasis), as well as rare indications such as lymphangioleiomyomatosis or
      sarcoidosis. TREATMENT AND OUTCOME: This article reviews the current strategies
      in the treatment of lung transplant recipients, surgical techniques, limitations
      of and outcome after lung transplantation.

PMID- 11957789
TI  - [Antioxidant therapy in vascular and renal diseases].
AB  - BACKGROUND: Reactive oxygen species are known to play an important role in the
      pathogenesis of several diseases including atherosclerosis. CARDIOVASCULAR
      EFFECT: Epidemiologic studies suggested a protective effect of antioxidative
      vitamins on atherosclerotic vascular diseases. However, prospective randomized
      studies failed to detect any beneficial effect of antioxidative vitamins,
      including tocopherol, on cardiovascular mortality. RENAL EFFECT: On the other
      hand, antioxidative therapies have been shown to prevent acute decreases of renal
      function induced by ischemia, contrast media or drugs. It is unknown whether
      antioxidative therapy also has beneficial effects in patients with chronic renal
      failure.

PMID- 11957790
TI  - [Treatment of cholestatic liver diseases].
AB  - MODE OF ACTION OF URSODEOXYCHOLIC ACID: In cholestasis, the impaired biliary
      secretion of toxic bile acids causes their accumulation in the liver and a
      subsequent hepatic failure. This bile acid-induced liver damage can be treated
      successfully with the atoxic ursodeoxycholic acid (UDCA). This bile acid is
      formed by 7-beta-epimerization of chenodeoxycholic acid by intestinal bacteria.
      It represents 1-3% of the total human bile acid pool. The hepatocellular content
      of toxic bile acids is reduced by UDCA. This protects the liver cell from injury
      by toxic bile acids. THERAPEUTIC RESULTS: The therapeutic effect of UDCA in
      primary biliary cirrhosis has been demonstrated. Furthermore, numerous other
      cholestatic liver diseases benefit from UDCA treatment. The autoimmune
      pathogenesis of cholestatic liver diseases, e.g., primary biliary cirrhosis,
      might reveal an additional beneficial effect of a combination therapy with UDCA
      and immunosuppressive substances.

PMID- 11957791
TI  - [Misinterpretation of elevated serum creatine kinase level in secondary
      hypothyroidism].
AB  - BACKGROUND: An elevation of serum creatine kinase (CK) level is diagnosed in
      about every third patient with hypothyroidism. This is a well-known laboratory
      finding which is described in all standard books of internal medicine.
      Nevertheless it is difficult to diagnose an indistinct elevation of serum CK if a
      cardiac event is excluded and especially diseases of skeletal muscle system are
      considered in differential diagnoses. Despite better knowledge a hypothyroidism
      is rejected in cases of normal basic TSH level although typical clinical signs in
      addition to myopathic pain are available. Describing three patients with
      secondary hypothyroidism we want to demonstrate the danger of overestimating
      laboratory parameters by ignoring clinical symptoms. CASE REPORT: Three patients
      came under medical observation due to unclear elevation of serum CK. Additional
      therapy with CSE inhibitors in two of the three patients led to the wrong
      conclusion as drug-specific side effect. The basic TSH level was normal in all
      patients, the main reason for late diagnosis of secondary hypothyroidism.
      CONCLUSION: Paying attention to clinical signs of hypothyroidism is elementary in
      cases of elevation of serum CK level. The secondary cause of hypothyroidism on
      basis of anterior pituitary gland insufficiency has to be included in
      differential diagnoses.

PMID- 11957793
TI  - [Recurrent epistaxis in a patient with aortic valve stenosis: a variant of Heyde
      syndrome?].
AB  - BACKGROUND: The Heyde syndrome describes the coincidence of aortic valve stenosis
      and intestinal bleeding. The pathophysiologic link between both entities has
      remained unclear so far. In several studies the intestinal bleedings have been
      attributed to angiodysplasia. Cessations of the intestinal bleedings following
      replacement of the aortic valve have been described by numerous reports. CASE
      REPORT: We describe the history of a 70-year-old man with a calcified aortic
      valve stenosis. In addition, he suffered from recurrent severe epistaxis over
      several years. Replacement of the aortic valve by bioprosthesis resulted in
      complete cessation of the nasal bleedings over a follow-up period of 6 years.
      CONCLUSION: This case report suggests that aortic valve stenoses may be
      associated with extraintestinal bleedings as well.

PMID- 11957792
TI  - [An unusual cause of pulmonary fibrosis in a 71-year-old patient].
AB  - CASE REPORT: A 71-year-old woman, suffering from spinal stenosis presented
      interstitial lung disease, albinism, and severe loss of visual acuity. On
      physical examination she showed tic-like automatism predominantly periorbital in
      the face and in the fingers. A computed tomography of the chest revealed typical
      findings of interstitial lung disease and additional mediastinal lymphomas and
      ground-glass attenuation in the lower regions of the lung. The findings of a
      transbronchial lung biopsy, presenting alveolar macrophages with ceroid-like
      material and platelet function studies proving slightly impaired platelet
      aggregation confirmed the clinical diagnosis of Hermansky-Pudlak syndrome.
      Sufficient pain control could be achieved without surgery and the patient was
      discharged home. 11 months after discharge, severe dyspnea and fever developed
      and finally the patient died of respiratory failure. CONCLUSION: The Hermansky
      Pudlak syndrome is a rare cause of interstitial lung disease. In general, the
      lung disease presents in younger patients, but it may emerge in the elderly as
      well. Alveolar macrophages containing ceroid-like material are typical findings
      in BAL or lung biopsy. Furthermore impaired platelet aggregation and bleeding
      diathesis may be present. Both findings are useful to identify this rare
      disorder.

PMID- 11957794
TI  - [Anti-C. pneumoniae IgG, IgA and IgM antibodies in patients undergoing coronary
      artery bypass grafting].
AB  - The aim of the study was to analyse the prevalence of anti-C. pneumoniae specific
      IgG, IgA and IgM antibodies in patients undergoing coronary artery bypass
      engraftment. Sera of forty-six patients aged from 40 to 74 years (mean 57.3) were
      examined just before the time of operation. Serum samples taken from 21 young
      healthy blood donors aged from 19 to 28 years (mean 22.4) and 23 sera taken from
      older blood donors aged 44-60 years (mean 54.7), were used as controls. Specific
      IgG, IgA and IgM serum antibodies were tested by the enzyme immunoassay kits (Lab
      systems, Helsinki). The prevalence of anti-C. pneumoniae IgG was determined
      within the studied groups, to be independent of their age. On the contrary, the
      level and seropositivity rate of specific IgA (63.0%), as well as a co-existence
      of IgA and IgG (60.9%) were significantly higher in coronary patients when
      compared to healthy blood donors. The presence of specific IgM (positive or
      borderline values) were detected in 23.9% of patients, whereas they were rarer
      found in healthy population. In the majority of coronary patients immunological
      markers of C. pneumoniae infection were found.

PMID- 11957795
TI  - [The examination of clinical prognostic importance of atrial and brain
      natriuretic peptide in patients with acute myocardial infarction].
AB  - Natriuretic peptides ANP, BNP and CNP with their receptors A, B, and C play an
      important role in maintaining the homeostasis. They have vasodilating, diuretic
      and natriuretic actions and regulate the systemic resistance. These peptides have
      been proved to contribute in pathogenesis of many diseases, for example heart
      failure, hypertension, acute coronary events or hepatic and renal insufficiency.
      The aim of our study was the estimation whether ANP or BNP could be markers of
      postinfarct heart failure in patients after thrombolytic therapy. The survey was
      made in 96 patients with acute myocardial infarction (AMI), who were treated in
      Department of Cardiology of University School of Medicine in Wroclaw. Patients
      were divided into 2 groups. The first group consisted of 56 patients with
      reperfusion after thrombolytic therapy and the second group created 40 patients
      without reperfusion. All patients were administered acethylsalicylic acid, 100 mg
      r-tPA (recombined tissue plasminogen activator) i.v. within 90 min and heparin in
      typical doses for the first 3-5 days. Venous blood samples for ANP and BNP
      estimation were taken before thrombolysis and then in 1st, 3rd, 5th and 30th day
      after treatment. We also measured the ejection fraction and activity of CPK and
      CK-MB in all the patients. Patients stayed under clinical observation for 12
      months. Our study showed that the levels of ANP and BNP increase in 1st day after
      treatment in all patients with AMI. The normalization of ANP and BNP occurs in
      3rd day after treatment in patients with reperfusion and in patients without
      reperfusion there are increased levels of these peptides even in 30th day. The
      increased level of BNP (> 160 pg/ml) is a significant risk factor of left
      ventricle systolic dysfunction, renewed AMI and sudden death in all patients with
      AMI after thrombolytic therapy whereas the increased level of ANP (> 100 pg/ml)-
      only in patients without reperfusion. Taking BNP as a marker of postinfarct heart
      failure it is possible to asses the risk of this complication in first day after
      thrombolytic therapy and choose the most proper treatment.

PMID- 11957796
TI  - [Topical treatment of bleeding post removed teeth in patients with prosthetic
      heart valves whose receiving long-term of oral anticoagulant therapy].
AB  - Removed teeth in patients receiving long-term oral anticoagulant drugs there are
      all the time live insure, very important and controversial problem in
      stomatological practice. Continuation of anticoagulation oral drugs exposure the
      patients so long haemorrhage while withdraw anticoagulant therapy to induce the
      risk of thromboembolism. The investigation were in 53 patients with prosthetic
      heart valves whose treated oral anticoagulant agents. The all patients have
      removed teeth without withdraw anticoagulant therapy. TachoComb administrated in
      alveoli post extraction teeth. The hemorrhage were in 4 (7.54%) cause.

PMID- 11957797
TI  - [Ischaemic heart disease risk factors in blue-collar women with different level
      of physical work].
AB  - The purpose of this study was to examine the level of some conventional coronary
      heart disease risk factors in blue-collar women and evaluate the link between the
      spreading of this risk factors and the level of physical work. The active
      smoking, exposure to environmental tobacco smoke, overweight and obesity,
      abnormal lipid levels and leisure-time physical activity were analyzed. 120 women
      of hard physical work and 57 women of light physical work in the age of 25 +/- 45
      y. were examined. The questionnaire and full physical examination were performed.
      In the group of hard physical work the prevalence of active smoking,
      environmental tobacco smoke exposure and mixed hyperlipidemia. The prevalence of
      hypercholesterolemia and obesity were observed in the group of light physical
      work. The high level of coronary artery disease risk-factors were found out in
      groups of blue-collar women with high and low level of occupational physical
      activity. It seems that lifestyle and diet plays an important role in spreading
      of the risk factors of CAD in blue-collar women.

PMID- 11957798
TI  - [Influence of therapy schedule on hospitalization frequency and prognosis in
      heart failure in 3 yrs. observations].
AB  - Patients with severe systolic heart left ventricle dysfunction determine a group
      loaded by high mortality. Continuous search for prognostic factors as well as
      treatment methods influencing a prognosis coming from clinical effects of applied
      prescriptions and survival in the mentioned group of patients can be observed in
      many published reports. In the presented work a retrospective analysis has been
      performed with regard to 106 patients with severe heart lesion: 72 cases with
      ischaemic disease, 20 cases with post-inflammation heart lesion, 7 cases with
      hypertension and 7 cases with idiopathic congestive cardiomyopathy. The main
      criterion including particular patient into the group under analysis was less or
      equal to 30% ejection fraction confirmed by echocardiographical examination and
      generally understand heart insufficiency in the clinical examination and
      laboratory tests. The observation period concerning patients qualified to the
      analyzed group incorporated 36 +/- 16.5 months. Influence of the parameters
      obtained from clinical, electrocardiographical, Holter monitoring, chest X-Ray,
      and serum concentration of both sodium (Na) and potassium (K) have been analyzed.
      Also the survival analysis has been performed for patients treated: according
      standard procedures, with addition of beta-adrenolytic drug, with addition of
      amiodaron, with addition of combination of both beta-adrenolytic drug and
      amiodaron. During the observation 64 patients have died (60%), 4 patients have
      had heart transplantation (Htx) performed (4%) and 38 patients survived without
      necessity of Htx (36%). Among investigated parameters there were following ones
      which proved their statistical significance in terms of prognosis evaluation:
      ejection fraction, features of pulmonary haemostasis, HR (heart rate), SBP
      (systolic blood pressure), serum concentration of both sodium (Na) and potassium
      (K). Much better therapy effects as well as longer survival have concerned
      patients with hypertension disease confirmed during the anamnesis. Comparison of
      the survival curves referring to the patients treated according to different
      schemes a positive trend in the direction of survival improvement has been
      observed. This trend however appeared in the group treated additionally with beta
      blocker and only in the outpatient follow-up. On the other hand a combination of
      both beta-blocker and amiodaron has been connected with improved both early and
      outpatient follow-up survival. The survival curves for patients treated with
      amiodaron only has been quite similar as in the case of patients treated
      according standard procedures. Addition of beta-adrenolytic drug or amiodaron or
      eventually both of these medicines has a significant influence into decrease of
      repeated hospitalizations in the group under investigation.

PMID- 11957799
TI  - [A value of compression therapy prophylaxis following surgery in patients
      suffering from chronic venous insufficiency].
AB  - The varices of the lower limbs and its complications are very common Surgical
      procedure which consists of ligatur of the venous tranks or stripping of them,
      ligation of perforating veins are basic methods of the treatment. After surgery,
      veins compression prevents secondary bleeding and above all, the development or
      recurrence of thrombosis The purpose of this study was the assessment of
      graduated compression stockings in prophylaxis of varicose vein disease
      recurrency. The study included 120 patients who underwent phlebectomy due to
      varicose veins. The period of follow up lasts 3 years and has been carried out in
      two groups. The first one was agreed to use compression therapy following
      surgery. The second group did not get any physical support to their legs.
      Compression class I and II: calf, thigh, panty medical stockings and were used.
      The first group of 60 patients (102 legs) wearing medical stockings following
      surgery have no either subjective or objective signs of venous insufficiency in
      long period of time after surgery. Statistical analysis pointed out marked
      significance between both groups of patients p < 0.001.

PMID- 11957800
TI  - [Evaluation of side effects after intrabladder instillations of preparations in
      patients with superficial bladder carcinoma].
AB  - Permanent increase in neoplasm incidence including also bladder neoplasms makes
      physicians to search for new forms and methods of treatment. Application of new
      preparations entails in many cases appearance of side effects which are difficult
      to fight off and thus must be monitored constantly. To avoid complications which
      in case of BCG application are very burdensome and sometimes dangerous for
      patient it is necessary to intervene in due time. In the years 1990-1998 in
      Department of urology, Ministry of Internal Affairs and Administration Hospital
      in Lodz, 241 patients were treated due to superficial bladder carcinoma. In this
      group in 145 cases after carcinoma electroresection BCG suspension intrabladder
      infusion were applied. In 42 patients epirubicin, in 16 adriblastin intrabladder
      instillations were performed; 32 patients did not receive any preparation. A
      detailed history was taken from the patients before each next infusion, whereas
      blood was collected for testing before the first infusion and on the seventh day
      after completion of the therapy. Material for studies was collected before the
      first intrabladder infusion and on the seventh day after 4-week cycle completion.
      Side effects of the applied preparations were presented basing on toxicity grades
      acc. to WHO and divided into subjective and objective ones. The observation
      period comprised the time from the first infusion to the seventh day after the
      last infusion. In the group of 145 patients with applied BCG suspension 836
      intrabladder instillations were performed. In 17 (12%) cases the treatment was
      stopped after 4 infusions due to intense dysuric symptoms. In the investigated
      group of patients strongly marked symptoms like polyuria (in 98% of patients),
      burning in urethra during miction (in 86%), haematuria and ill-being were
      observed. Objective symptoms were significantly marked and were not of importance
      in further management. In group II (epirubicin) and III (adriblastin) both
      subjective and objective effects were of insignificant percentage and were not of
      importance in the continuation of the treatment of superficial bladder carcinoma.
      Accurate subjective examination, careful analysis of the observed unfavourable
      symptoms, their intensity, close co-operation of the physician with the patient
      concerning full information on possible complications and side effects and
      personal procedure with them allow for safe and effective treatment of
      superficial bladder carcinomas with both BCG suspension and anthracycline
      antibiotics (in the form of intrabladder infusions).

PMID- 11957801
TI  - [Selenium plasma concentrations in children with celiac disease in different
      stages of diagnosis].
AB  - Selenium is an important nutritional factor of human diet. Epidemiological and
      experimental data indicate that low selenium level can be associated with
      increased risk of cancer. On the other hand there are some evidence that patients
      with celiac disease can present selenium deficiency and increased risk of certain
      malignancies. Therefore the aim of study was to evaluate plasma selenium levels
      in children with celiac disease. The level of selenium was estimated by flame
      atomic absorptiometry method according to Whiteside. Celiac disease was diagnosed
      according to ESPGHAN criteria. Obtained results indicate that in celiac disease
      low plasma selenium levels are especially marked at preliminary stage of
      diagnosis and following low compliance to the gluten free diet. Children with
      this sickness may need supplementation of their diet with selenium.

PMID- 11957803
TI  - [Seronegative myasthenia gravis].
AB  - Myasthenia gravis (MG) is an acquired autoimmune disorder of neuromuscular
      transmission in which antibodies to acetylcholine receptor (AChRAB) attack the
      postsynaptic membrane of the neuromuscular junction. Circulating AChRAB are
      present in 80-90% of patients with the generalised form of MG and in 55-70% of
      patients with the ocular form of disease. Contrary in 10-20% of patients with
      typical symptoms of MG, the standard immunoprecipitation test for AChRAB is
      negative. Those patients contain a group of seronegative MG (SNMG). The aim of
      this study was the examination of frequency of SNMG in patients with different
      types of MG according to Osserman's classification. The establishment a relation
      between the fact of non-marking AChRAB in the plasma and the clinical state of
      the patients was also done. 74 patients with diagnosed MG and 30 healthy controls
      were evaluated. The diagnosis of MG was based on clinical features and one or
      more of the following factors: response to edrophonium chloride,
      electrophysiologic studies and demonstration of circulating AChRAB. In all of
      persons standard neurological examination was performed and measurement of the
      level of AChRAB was done. AChRAB were determined with a radioimmunoassay using
      125-l-alpha-bungarotoxin. The myasthenic patients were classified according to
      Osserman's classification. The Oosterhuis' personal disability scoring system was
      used to indicate disease severity. In all of healthy controls the levels of
      AChRAB were within normal standards. 27% of myasthenic patients were
      seronegative. Statistically significant differences in the frequency of
      occurrence cases with SNMG in different types of MG according to Osserman have
      not been observed. The differences in the frequency of occurrence cases with SNMG
      in different classes according to Oosterhuis scale were indicated, but they did
      not reach statistical function. Negative titers of AChRAB can be found in all
      types of MG irrespective of the clinical state of the patients. It proves the
      diagnostic difficulties in MG and shows that the results of the measurement of
      AChRAB should be interpreted in relation with results of other examinations used
      in MG diagnosis.

PMID- 11957802
TI  - [Dynamic of IL-6 and IL-8 concentrations in patients after surgery treated with
      total parenteral nutrition].
AB  - Exaggerated cytokines productions and development of systemic inflammatory
      response (SIRS) is the most common cause of postoperative complications and death
      after major abdominal surgery. The present study was conducted to investigate
      alterations in systemic production of interleukin-6 (IL-6) and interleukin-8 (IL
      8) after total parenteral nutrition (TPN) in surgical patients. Plasma
      concentrations of IL-6 and IL-8 were measured in 22 patients (10 treated with TPN
      and 12 without TPN) before major surgery and on the days 1, 3, 7, 10 and 14-16
      after, by ELISA test (indications for surgery: stomach, pancreatic and colon
      carcinoma, complications of IBD and acute pancreatitis). There were no
      differences between preoperative levels of IL-6 and IL-8 in the examined groups
      of patients. The highest (on the days 1, 3, 7, 10: 268.3 (p = 0.002), 41.9 (p =
      0.03), 122.6 (p = 0.009), 29.3 (p = 0.03) pg/ml respectively) and longer lasting
      significantly elevated level of IL-6 was observed in the group of patients after
      major surgery without TPN. In the group of patients received TPN (with glutamine)
      there was a significantly increased but in comparison with group of patients
      without TPN, significantly lower level of IL-6 on days 1 and 7 (103.4 and 34.7
      pg/ml respectively, p = 0.01). There was no significant change in postoperative
      concentration of IL-8 after major surgery in the group of patients treated with
      TPN. The level of IL-8 was significantly elevated (p = 0.01) in the group of
      patients without TPN on day 1 and 3 following surgery. The IL-8 level in the TPN
      group vs. group of patients without TPN was significantly lower on day 1 after
      surgery. After TPN concentration of cholesterol was significantly higher and CRP
      level significantly lower. We conclude that TPN improved immunological response
      to major surgical trauma by reduction of the inflammatory response.

PMID- 11957804
TI  - [Basic three-dimensional rendering techniques used in diagnostic imaging].
AB  - The paper presents an overview of basic three-dimensional techniques used in
      computed tomography, magnetic resonance imaging, nuclear medicine, and
      ultrasound. Data acquisition and processing methods, current applications, and
      development trends are discussed.

PMID- 11957805
TI  - [Clinical course of borreliosis in children].
AB  - Clinical picture of Borrelia burgdorferi infection has been presented in 45
      children, aged 2-16 years from Lodz region. The analysis showed significant
      domination of cases with affected central and peripheral nervous system (44.4%)
      and rather unspecific symptoms such as: fever (20%) or headache (13.3%).
      Peripheral cranial nerves paralysis and symptoms of cerebrospinal meningitis
      dominated among children with neuroborreliosis. Unlike descriptions concerning
      adults, majority of the observed symptoms were changes characteristic for I and
      II stage of the disease. Dermatosis was found only in 1 child and symptoms of
      arthritis in 2 of them. Contact with tick was stated in 52% of the analysed
      children. Incidence of the disease occurred throughout the whole year, more
      frequently in summer and autumn months.

PMID- 11957806
TI  - [Do preterm infants differ from healthy newborns by endothelin para/endocrine
      function?].
AB  - We measured plasma concentration of endothelin-1 (ET-1), nitric oxide metabolites
      (NOx) and von Willebrand factor (vWF) in maternal and umbilical cord blood in 11
      spontaneous (SN), 11 elective cesarean section (CC) and 13 preterm deliveries.
      Plasma concentrations of ET-1 in umbilical cord blood of preterm infants and
      systemic blood withdrawn 4 days after birth was higher then in respective healthy
      infants delivered by natural forces or elective cesarean section. Positive
      correlation were found between ET-1 and NOx (p < 0.05) and between ET-1 and vWF
      (p < 0.05) in maternal blood with preterm delivery. In umbilical cord of preterm
      infants a negative correlation between ET-1 and Apgar score was noticed. Higher
      concentrations of ET-1, NOx and vWF found in umbilical cord blood of preterm
      infants as compared with respective values assessed in healthy infants delivered
      per vaginam or by cesarean section respectively seem to be induced by hypoxia.

PMID- 11957807
TI  - [Low-symptomatic pheochromocytoma].
AB  - We present the patient with 1-month history of mild hypertension, who was
      admitted to our department with suspicion of coronary heart disease. He had
      family history of hypertension and coronary heart disease, hyperlipidaemia and he
      has been smoker for several years. During the diagnostic exertion test chest pain
      together with an unusual high blood pressure was found (240/140 mmHg). The
      results of catecholamines and their metabolites in 24-urine collection, abdominal
      ultrasonography and NMR revealed pheochromocytoma in the left adrenal gland,
      which was removed successfully. Particular clinical examination allowed to
      include the patient to the group with low-symptomatic pheochromocytoma. Abdominal
      USG, which had been done prior to the exertion test, didn't reveal any incidental
      tumor in the adrenal glands. The abnormal hypertensive reaction during exertion
      test was the main decision of the urine catecholamines and their metabolites
      determination. Pheochromocytoma should be included to the differential diagnosis
      in all patients with chest pain and high blood pressure during diagnostic
      exertion test.

PMID- 11957808
TI  - [Endothelin and essential hypertension].
AB  - Vascular endothelium is of importance in an arterial function having its own
      metabolic and secretory activity. Endothelins are a group of peptides with 3
      isoforms: E-1, E-2 and E-3. Endothelin-1 is the main one, synthetized in
      endothelial cells, muscular coat of arterial wall as well as in heart, kidneys
      and central nervous system. The article presents the important role of endothelin
      in supporting the basal vascular tone, what could be compared only to influence
      of sympathetic nervous system and nitric oxide. The paper pays attention to
      participation of endothelins in the pathophysiology of essential hypertension. It
      calls also our attention to possibility of production of non-selective endothelin
      receptors blockers, which mediate relaxation of resistance arteries and have
      hypotensive effect, what could be useful in many cardiological diseases.

PMID- 11957809
TI  - [The role of TNF-alpha in the etiopathogenesis of heart failure].
AB  - Clinical evidence demonstrates participation of several cytokines in cardiac
      heart failure pathogenesis, in particular tumor necrosis factor-alpha (TNF
      alpha), which induces left ventricular dysfunction, acute pulmonary edema and
      congestive cardiomyopathy. Increased levels of TNF-alpha in patients with heart
      failure were proved and may have prognostic significance. Absent in normal
      myocardium, produced in the myocardium in response to volume overload, TNF-alpha
      can depress cardiac function directly and indirectly by induction of nitric oxide
      synthase produced by macrophages, cardiac myocytes and other cells. The most of
      TNF-alpha effects are performed by two receptors termed as TNF-RI and TNF-RII
      identified on the surface of many cells. The extracellular domain fragments of
      both receptors shed from cell surface can be detected as soluble forms sTNF-RI
      and sTNF-RII in the urine and blood, and their blood levels in patients with
      severe heart failure are elevated. There are various pharmacological agents that
      block the biological effects of TNF-alpha, however only two of them have been
      used in patients with heart failure: pentoxifylline and etanercept. Encouraging
      effects of this studies must be regarded as provisional because of relatively
      small numbers of treated patients. Preliminary results of other randomized,
      multicenter and in large patients populations trials, planned till 2002 year
      indicate the possibility of novel anti-TNF strategies in heart failure; treatment
      is well tolerated and can be effective. It is thought, that recombinantly
      produced TNF-alpha soluble receptor being now evaluated clinically can determine
      the progress in heart failure treatment.

PMID- 11957810
TI  - [The safety of patients and staff in the operating room].
AB  - The risk of postoperative infection is determined by a number of factors
      including the underlying health of the patient, the type of surgery and the
      environment in which the procedure take place. The predominant infective
      organisms are Staphylococci. Coagulase-negative staphylococci are regarded as
      emerging pathogens, especially in clean surgery. The operating team is the major
      source of the contaminated bacteria. Bacteria dispersed from the skin is of
      greater importance than bacteria from the respiratory tract, so masks are not
      always necessary in the theatre during an operation except by those at the table.
      Masks that function as protective barriers are another emerging issue. Due to a
      greater awareness of HIV and other blood-borne viruses, masks are taking on a
      greater role in protection health care workers from potentially infectious blood
      and body fluids. Bloodborne infection pose a large risk to healthcare workers.
      The incidence of occupational HBV infection has decline as a result of vaccine
      induced immunity. Future vaccines against HIV and HCV would be a boon to
      healthcare workers.

PMID- 11957811
TI  - [Antigens (CEA and CA 19-9) in diagnosis and prognosis colorectal cancer].
AB  - carcinoembryonic antigen (CEA) was first described more than three decades ago,
      when its presence was demonstrated in fetal gut tissue and in tumors from
      gastrointestinal tract. Subsequently, CEA was detected in the circulation of
      patients and recognized as a serum marker for colorectal cancer. This tumor
      marker has not been advocated as a screening test for colorectal cancer, however
      a preoperative CEA serum level is useful for diagnosis and prognosis of
      recurrence and survival in colorectal cancer patients. The levels of CEA
      increased with increasing tumor stage. Expression of carbohydrate antigen (CA 19
      9) has been described in various malignancies and also in colorectal cancer. This
      antigen also has not been advocated as a screening test for colorectal cancer.
      The levels of CA 19-9 increased in advanced stages of colorectal cancer. Despite
      its lower sensitivity than CEA in early stages of colorectal cancer, the
      combination of both antigens can provided more information than CEA alone for
      prognosis of recurrence and survival in those patients.

PMID- 11957812
TI  - [Dental mask of gastroesophageal reflux disease].
AB  - In the last few years the interest of extraesophageal symptoms of
      gastroesophageal reflux disease is getting greater and greater. Because of it is
      often appearance, this disease is noticed not only by gastroenterologists, but
      also other doctors and dentists. They think that pathological, backward reflux of
      esophagus in many cases can be responsible for dental organ disease. Clinical
      research proofs that often pouring the sour mixture from the stomach into the
      esophagus and then to mouth can cause a diminution in the teeth such as: erosion
      and decay. The background agum and tounque can be gastroesophageal reflux
      disease. acquantance with this facts among the dentists can help to make a
      diagnosis and treat well patients with a pathological reflux of esophagus.

PMID- 11957813
TI  - [Comparison of the clinical usefulness of magnetic resonance (MR), computer
      tomography )CT) and radiculography (R) in diagnosing lumbar discopathy].
AB  - The aim of the study was an assessment of the usefulness of magnetic resonance
      imaging (MRI), computed tomography (CT), and radiculography (R) in the diagnosis
      of lumbar discopathy. The accuracy of MRI, CT, and R for the diagnosis of lumbar
      herniated nucleus pulposus ws compared prospectively in 120 patients, undergoing
      surgical exploration. MRI was the most accurate test (100%) compared with CT
      (95%) and R (92.5%). The false positive rate was lowest for MRI (0%), followed by
      CT (5%) and R (7.5%). MRI proves very favorable compared with other currently
      available imaging modalities for diagnosis of lumbar herniated nucleus pulposus
      which allows to differentiate hernia and protrusion. MRI is noninvasive, has no
      known side effects and no radiation exposure. It is the procedure of choice for
      the radio-diagnosis of lumbar disc herniations.

PMID- 11957814
TI  - [Mechanisms determining the occurrence of microalbuminuria in patients with acute
      ischemic stroke].
AB  - Microalbuminuria is more prevalent in patients with risk factors for
      cardiovascular diseases and reflects the widespread vascular damage predisposing
      to atherosclerosis. It is also found in acute clinical conditions, e.g.
      myocardial infarction, pancreatitis and stroke, and predicts poor outcome. The
      mechanism leading to increased albuminuria in these conditions is unknown,
      therefore we designed the study to investigate the relationship between increased
      urinary albumin excretion in acute stroke and biochemical markers of stress and
      inflammatory reaction as well as markers of endothelial damage. Sixty patients
      with first-time ischemic stroke, admitted within 24 hours to the stroke unit took
      part in the study. We excluded patients with diabetes, infection, nephropathy and
      abnormal urinalysis. Neurological deficit was assessed on admission and after 24
      hours by Scandinavian Stroke Scale. Daily urinary albumin excretion on Day 2 was
      measured using the immunonephelometric method. The serum cortisol concentration
      was measured on Day 1 at 6.00 AM, 10.00 AM, 6.00 PM and 10.00 PM. Daily urinary
      excretion of epinephrine and norepinephrine was measured on Day 1 and on Day 3.
      We assessed also hematocrit, ESR, serum glucose and fibrinogen, leukocytosis,
      thrombocytosis and von Willebrand factor activity. Microalbuminuria was found in
      46.7% of patients. There was no difference between patients with micro
      albuminuria and those without it regarding sex, age and the prevalence of risk
      factors for stroke. Patients with micro-albuminuria had greater urinary excretion
      of epinephrine on Day 1. We did not find any differences regarding von Willebrand
      factor activity, serum cortisol concentration or other assessed variables. In
      logistic regression analysis the urinary excretion of epinephrine on Day 1 was
      the only independent variable predicting the occurrence of microalbuminuria in
      patients with acute ischemic stroke.

PMID- 11957815
TI  - [The comparison of selected parameters of structure and function of the
      cardiovascular system in patients with functioning graft on maintenance
      hemodialysis during a one year period].
AB  - Successful renal transplantation allows to correct most of the abnormalities that
      lead to cardiovascular system injury in chronic uremia. The aim of the present
      study was to analyze selected anatomical and functional parameters of the heart
      using echocardiography. The study was conducted prospectively in two groups of
      patients: 73 subjects with functioning graft and 53 patients on maintenance
      hemodialysis. Obtained results were compared between those two groups at the
      start of the study and later on after 6 and 12 months of follow-up. Post
      transplant patients were included into the study 11 +/- 6.4 months after
      successful transplantation. Mean dialysis period prior to transplantation was 35
      +/- 21 months. Patients in the control group were dialyzed for mean 54 +/- 25
      months. The prevalence of various diseases of the cardiovascular system was equal
      in both groups of patients (most frequently diagnosed was hypertension). There
      was no difference in ejection fraction within groups during the whole study
      period, however the value of this parameter was higher among patients with
      functioning graft at the beginning of the study (p < 0.01) as well as after 6 and
      12 months (p < 0.001) as compared to patients on dialysis. The prevalence of
      different morphological abnormalities of the heart, such as concentric
      hypertrophy, left ventricle dilatation, valve dysfunction as well as
      calcification of various structures, was equal in both groups of patients at the
      beginning of the study. In 87.7% of patients with functioning graft, left
      ventricle hypertrophy was diagnosed at the beginning of the study (mean LVMI
      value 176.9 +/- 55.5 g/m2) and this percentage decreased to 63% after 6 months
      (LVMI 155.8 +/- 60.3 g/m2; p < 0.001 vs. baseline) and 53.4% after 12 months
      (LVMI 141.6 +/- 62.1 g/m2; p < 0.001 vs. baseline). Regression of initial left
      ventricle hypertrophy, although less pronounced was also present among patients
      on maintenance dialysis. There was no difference in LVMI value between the
      studied groups at the beginning of the study, whereas after 6 and 12 months of
      observation it became significantly lower in patients with functioning graft
      (155.8 +/- 60.3 vs. 179.5 +/- 50.9 g/m2; p < 0.01 and 141.6 +/- 62.1 vs. 176.2 +/
      50.5 g/m2; p < 0.001). Based on obtained results we conclude that successful
      renal transplantation promotes the normalization of a number of echocardiographic
      parameters, especially leads to regression of left ventricle hypertrophy. Renal
      transplantation seems to be an optimal method of treatment in patients with end
      stage renal failure, considering structure and function of the cardiovascular
      system.

PMID- 11957816
TI  - [Instruction of patients and a delay of treatment in myocardial infarction and
      unstable angina in the Krakow Program of Secondary Prevention of Ischaemic Heart
      Disease (IHD)].
AB  - Shortening the time between the onset of pain and start of the efficacious
      treatment is an important mean to lower case-fatality in myocardial infarction
      (MI). The goal of this publication was to assess: 1) current time between the
      onset of pain and: a) calling medical service by the patient b) first examination
      by a doctor, and c) first administration of intravenous treatment, 2) reasons of
      the delay in calling medical service by the patient, 3) whether patients with a
      diagnosis of ischaemic heart disease (IHD) prior to hospitalization were
      instructed how to behave in case of chest pain, and 4) whether instructing how to
      behave in case of chest pain was related with a time between the onset of pain
      and calling medical service by the patient. Studied group were 515 patients
      hospitalised in 6 in-patient clinics of cardiology with MI or unstable angina
      (UA) or hospitalised for first PTCA or CABG, 427 (83%) agreed to participate, out
      of whom 184 had MI or UA including 110 patients having typical chest pain. In
      hospitalized patients with MI or UA with typical chest pain 62% received
      intravenous treatment within first 4 hours after the pain onset. 35% patients
      received first intravenous treatment later than 6 hours after the onset of pain
      and out of them 2/3 after 12 hours. The main component of the delay was the long
      time between the onset of pain and the call for medical service. 46% patients
      called for medical service later than 1 hour after the onset and in 80% of them
      the reason was lack of knowledge on the risk and how to behave in case of chest
      pain. Patients who earlier received instruction had four times higher chance to
      call medical service within the first hour after the onset of pain (Odds Ratio =
      4.11, 95% confidence interval 1.13-15.0). Only half of all patients hospitalised
      due to acute episode of IHD or for revascularization procedures received
      intensive instructions from a doctor. Adopting a detailed instruction on how to
      behave in case of chest pain as a standard procedure for patients with IHD may be
      an important mean to lower case-fatality in MI.

PMID- 11957817
TI  - [Overweight--problem in pediatric patients. Part I. Obesity as a risk factor for
      metabolic disturbances].
AB  - Obesity in adults is associated with multiple disorders of glucose, insulin and
      lipid homeostasis. Children with early onset of obesity appear to be an
      interesting group for study of early alterations in human obesity. However only
      few such studies have been performed. In this group, many data show that obesity
      in childhood and adolescents is associated with the development of risk factors
      for cardiovascular and metabolic diseases. The objective of this study was to
      determine contribution of obesity to the development of impaired glucose
      tolerance, dyslipidaemia and hormonal imbalance. Body mass index (BMI) greater
      than 25 kg/m2 has recommended as the cutoff value respectively for overweight. In
      obese patients insulin secretion, glucose and lipid metabolism was impaired.

PMID- 11957818
TI  - [The role of glucose and reactive oxygen species in the development of vascular
      complications of diabetes mellitus].
AB  - Several mechanisms seem to be involved in the development of oxidative stress in
      the presence of elevated glucose concentrations, namely glucose autoxidation,
      protein glycation, and the polyol pathway. In diabetes patients reactive oxygen
      species and advanced glycation end products are able to alter vascular function
      and disturb cellular homeostasis especially by lipid peroxidation, changes in
      extracellular matrix and inhibiting synthesis and action of nitric oxide.

PMID- 11957819
TI  - [Familial LCAT deficiency].
AB  - Familial deficiency of lecithin-cholesterol acyltransferase (LCAT) was described
      by Norum and Gjone in 1967. LCAT (EC 2.3.1.43) is a serum enzyme involved in
      reverse cholesterol transport. LCAT deficiency is associated with percentage
      increase of free cholesterol and decrease of esterified cholesterol, and
      disturbances in lipoprotein particles structure, because cholesterol esters form
      the lipoprotein core. Lipid disorders involve also other organs, such as kidneys,
      cornea and erythrocytes; with clinical manifestations of proteinuria, usually
      associated with renal insufficiency, corneal opacities and haemolytic anemia.
      Gene encoding LCAT is localized in region q 21-22 on chromosome 16. It consists
      of 6 exons, divided by 5 introns and spans 4.2 bp. Familial LCAT deficiency is an
      autosomal recessive disorder. In LCAT deficient patients several mutations in all
      6 exons have been described. Clinical manifestations of familial LCAT deficiency
      are highly variable, although no or only low LCAT activity is present and this
      may suggests that expression of the disease is modulated by additional
      environmental factors and genes of minor importance.

PMID- 11957820
TI  - [Fibrate influence on lipids and insulin resistance in patients with metabolic
      syndrome].
AB  - Dyslipidemia, central obesity, hyperinsulinemia and insulin resistance, arterial
      hypertension, impaired glucose tolerance and increased thrombogenicity are the
      main features if metabolic syndrome. Metabolic syndrome is associated with
      increased cardiovascular risk. Fibrate administration in metabolic syndrome,
      apart from favourable influence on lipid profile was associated with decrease of
      hyperinsulinemia nad insulin resistance, reduction of systolic and diastolic
      blood pressure and decrease of hemostatic factors, strong predictors of increased
      coronary risk--fibrinogen, an acute phase reactant and factor VII was observed.
      Fibrate treatment was associated with slight decrease of body weight. These
      favourable effects of fibrates may make them particularly suitable for treatment
      of dyslipidemia in persons with metabolic syndrome.

PMID- 11957821
TI  - [Renal involvement in vasculitis].
AB  - Systemic vasculitides are a heterogenous group of diseases, characterized by
      inflammation of blood-vessel walk. In the course of different types of vasculitis
      renal involvement is quite often present. Renal dysfunction may manifest as a
      component of multi-system disease or as the first clinical expression of
      vasculitis. Presented paper shows the clinical picture of different form of
      vasculitis and possibilities of their urinary tract manifestations.

PMID- 11957822
TI  - [The ubiquitin system--structure and function].
AB  - Current opinions connected with the role and significance of ubiquitous proteins-
      ubiquitins (Ub) were discussed. Genetic determination of ubiquitins and their
      expression in nature were considered. Thymic ubiquitin complex, as an extract
      from calf thymus gland (TFX) was also presented. Very important biological
      activities in some experimental models and usefulness of TFX in medical practice
      were presented.

PMID- 11957823
TI  - [Histocompatibility HLA system of man. Considerations in the light of current
      concepts. VI. HLA-G antigen polymorphism].
AB  - The results of hitherto researches over gene products of HLA-G locus, i.e.
      membrane bound forms (M*HLA-G) and soluble forms (S*HLA-G) were verified. Current
      opinions connected with synthesis and molecular organisation of five HLA-G
      isoformic molecules (HLA-G1, -G2, -G3, -G4, -G5) were presented. The polymorphism
      of HLA-G gene and its expression were qualified. Special attention has been
      turned on presumably significant function of HLA-G in maintenance of maternal
      placenta immunological tolerance, binding of monomeric peptides, and antigens
      presentation, taking into consideration cytomegaloviruses (CMV). In spite of
      significant progress in the understanding of mutual relationship between mother
      and placenta many phenomena with participation of HLA-G gene products, especially
      in pathological conditions, are still unknown.

PMID- 11957824
TI  - [Abrikosov's tumor of the esophagus].
AB  - The authors are reporting a case of Abrikosov's tumor of the oesophagus
      (myoblastoma granulocellulare, granular cell tumor, GCT). Due to the rare
      incidence of these lesions, they are also presenting general state of knowledge
      on these particular tumors based on the literature, diagnostic methods and
      treatment.

PMID- 11957825
TI  - [Small intestine obstruction caused by primary malignant neoplasms].
AB  - The authors presented 4 cases of primary malignant neoplasm of the intestine
      caused by small intestine obstruction. These patients underwent emergency
      surgery. In all cases, a segmental resection of the intestine was performed.
      There were two cases of adenocarcinoma and two cases of carcinoid. Three patients
      were complementarily treated using chemotherapeutics. One of them died two years
      post operation. The last three patients survived 0.5-5 years post operation.

PMID- 11957826
TI  - [Ulcerative colitis concomitant with pyoderma gangrenosum and erythema nodosum-
      presentation of two cases].
AB  - Authors present case of a 28-year old woman with skin symptoms of pyoderma
      gangrenosum and ulcerative colitis seriously advanced. The patient benefited from
      wide resection of the colon and steroid therapy. The other patient was 23-year
      old woman with ulcerative colitis concomitant with skin changes of erythema
      nodosum. In this case steroid therapy gave also a very good effect. We tried to
      find pathogenetic connection between these diseases based on the reports from the
      medical literature.

PMID- 11957828
TI  - Brushing up on dental history: a quick guide to who's who.

PMID- 11957827
TI  - [Establishment and development of the self-governed health case system in the
      Austrian sector of Poland].
AB  - Transformation and development of organisational matters, characteristic for the
      18th and 19th centuries, included the issue of public health care. The
      development of economy, social and medical sciences changed the understanding of
      joint responsibility of the state for public health. The Teresian-Josephine
      reforms in Austria, concerning public issues, including the sanitary
      epidemiological matters, were enforced in the areas of Polish annexed territory
      in 1772 and 1795. The normative regulations for Galicia and Lodomeria from 1773,
      1861, 1891 established the responsibilities and rights for medical practice,
      activities of sanitary institutions and general medical care for the society.
      Austrian sanitary legislation created central institutions and self-governed
      local structures, responsible for public health. Introduction of modern local
      administration had a deciding effect on the development of self-governed
      institutions in closed and open health care system. Apart from sanitary national
      administration, public health care matters were governed by local-governed
      authorities of the insurance sector and private subjects. This advanced
      decentralisation and handing of health care matters to local self-governments
      shaped the new system of public health care.

PMID- 11957829
TI  - The Star Wars of dentistry. Using the erbium laser to treat tooth decay.

PMID- 11957830
TI  - Asset protection: offshore trusts.

PMID- 11957831
TI  - Jumpin' Jack Flash. It's a Nash Bash gas.

PMID- 11957833
TI  - Looking back. Lucy Hobbs Taylor.

PMID- 11957832
TI  - In other words. Say it again.

PMID- 11957834
TI  - Prevention key to improving women's health.

PMID- 11957835
TI  - Endorsing JCAHO's Sentinel Event Alert. Report on ventilator deaths and injuries
      echoes ECRI's long-held views.

PMID- 11957836
TI  - Spurious ECG signals during hemodialysis.

PMID- 11957837
TI  - Rainout from a Fisher & Paykel heated humidification system can shut down certain
      ventilators.

PMID- 11957838
TI  - Sharps safety. A practical guide for establishing and evaluating a sharps injury
      prevention program.

PMID- 11957839
TI  - On being a colleague....

PMID- 11957840
TI  - Rapid prenatal diagnosis of trisomies 13, 18, 21 and sex chromosome anomalies by
      fluorescence in situ hybridization: a year's experience.
AB  - The present paper summarizes our first 12 months' experiences of rapid prenatal
      diagnosis using commercially available diagnostic fluorescence in situ
      hybridization (FISH) probes for chromosomes X, Y, 13, 18 and 21. The data clearly
      demonstrate that the advantage of using FISH as an adjunct technique is the fast
      and reliable determination of the common fetal chromosomal aneuploidies; the
      results are available in less than 24 hours instead of the 7-14 days with
      standard techniques.

PMID- 11957841
TI  - 64 year-old male with non-reducible left upper quadrant abdominal mass: a
      clinicopathologic correlation conference from the University of Oklahoma College
      of Medicine.

PMID- 11957842
TI  - Anterior interosseous nerve syndrome: a case report.
AB  - A patient presented with anterior interosseous nerve syndrome that did not
      respond to nonoperative treatment. At surgery, nerve compression was found to be
      from an anomalous fibrous band of the flexor digitorum superficialis extending to
      the brachialis muscle fascia and separate from the normal arcade passing over the
      median nerve. Additionally, there was a venous ring encircling the nerve at the
      level of the anomalous arcade. The patient's muscle weakness recovered after
      nerve decompression and releasing the anomalous structures.

PMID- 11957843
TI  - Erythema migrans and the differential diagnosis of annular erythema.
AB  - The diagnosis of Lyme disease (LD) or Lyme borreliosis is often based on the
      recognition of erythema migrans (EM) because its clinical appearance precedes
      systemic manifestations of the disease and the antibody response. The clinical
      basis and variable presentation of EM leave room for diagnostic error and, as a
      consequence, potential long-term repercussions such as rheumatic, cardiac,
      ophthalmic, or neurologic complications. Most cases are reported in the
      Northcentral and Northeastern states. In areas where LD is not endemic, the
      differential diagnosis of annular erythema may not list EM highly, although all
      the features of a lesion may fit the typical description of EM. Therefore, a
      complete understanding of LD and its clinical presentation are key in making a
      diagnosis, especially in areas with low incidence. We present a hypothetical case
      report of EM from Oklahoma, a state with low incidence of LD, for the purposes of
      review of this entity and the differential diagnosis of annular erythema.

PMID- 11957844
TI  - Ethical, legal and scientific issues concerning human cloning.

PMID- 11957845
TI  - Sixty-three-year-old American Indian female with left upper lobe lung mass and
      pancreatic mass: a clinicopathologic correlation conference from the University
      of Oklahoma College of Medicine.

PMID- 11957846
TI  - Healthcare options for Medicare beneficiaries.
AB  - Medicare beneficiaries often need to purchase supplemental coverage or join a
      federally approved HMO to gain prescription coverage and other benefits. In
      general, obtaining additional coverage may include a premium payment that is
      dependent on age. There is an array of choices in Oklahoma.

PMID- 11957848
TI  - The near-future of office-based prevention a dream of seamless integration of
      preventive clinical service into every doctor visit.

PMID- 11957847
TI  - Canadian prescription drug importation programs contain risks for Oklahoma
      physicians.
AB  - In response to high prescription drug prices in the United States, several
      services have attempted to make prescription drugs available directly from
      Canadian pharmacies, which often can sell the drugs at a significantly cheaper
      price. Normally, a patient must have his physician become directly involved in
      this process in order to import the drugs from Canada. Although it is
      understandable for a physician to want to help a patient in this manner, there
      are several potential risks for an Oklahoma physician participating in these
      programs. In addition, there is significant risk the patient may not be getting
      the drugs prescribed.

PMID- 11957849
TI  - Oklahoma City and Tulsa Metropolitan Medical Response System.
AB  - The tragic loss of lives on September 11 followed by the Anthrax contaminations
      reinforced the need for work already underway through the Metropolitan Medical
      Response System (MMRS). Through leadership from the Medical Director for the
      Medical Control Board and EMSA, Oklahoma City and Tulsa have been the
      beneficiaries of nearly $1.5 million dollars in funding to prepare for nuclear,
      chemical or bioterrorism. The two Oklahoma cities were among the second wave of
      cities invited in 1999 to participate in the federally funded program for
      Metropolitan Medical Response. Many of the requirements of the contract have
      already been met under the capable guidance of Michael Murphy, a 23 year
      paramedic with 12 years of management experience with EMSA. Among the plans
      completed or underway are a Development Plan, MMRS System Plan, Forward Movement
      of Patients Plan, Pre-hospital Response Plan, a Biological Incident Plan, a
      Hospital Response Plan, a Training Plan and an Equipment and Pharmaceutical Plan.
      Coordinated planning between the two cities bring the added benefit of seamless
      sharing of personnel between both ends of the turnpike should a disaster impact
      one rather than both communities.

PMID- 11957850
TI  - Telehealth practice in home care. Synopsis of the 2000 US Telenursing role study.
AB  - Any use and integration of new technology into nursing should be accomplished in
      a purposeful and meaningful manner. The synopsis reported here provides the
      health care arena with nurses' response to devices and technologies, their
      emerging roles in the health care system as a result of telehealth technology,
      and the impact of new technology on patients and health care enterprises.

PMID- 11957851
TI  - VNA of Brooklyn's point-of-care technology. Evolution and use.
AB  - To adequately address care, cost, and compliance factors, agencies must radically
      change the method and the frequency in which they collect and analyze patient
      data. After thorough review of its operations, the management of Visiting Nurse
      Association of Brooklyn determined that the last bastion of inefficiency within
      the agency was its data collection process at the point of care. Agency
      administrators decided to focus on this area by eliminating its paper-based point
      of-care system with a goal of reducing costs and increasing cash flow.

PMID- 11957852
TI  - Lessons learned from a telehomecare project.
AB  - This article provides an update on the results of the Telehomecare Project, a
      demonstration funded by the US Department of Commerce through its Technology
      Opportunity Program. The goal of the project was to demonstrate and evaluate the
      use of telephone-based information technology (IT) in the provision of home
      health services. This effort was described in the August, 1999 (vol. 18, no. 8)
      issue of CARING.

PMID- 11957853
TI  - High tech. High touch. John Naisbett's world view.
AB  - History will record that 20 years ago, a man named John Naisbett made a
      contribution which literally changed the world, with his book Megatrends. It
      changed the way that we think about the world. It changed the way that we think
      about ourselves. A distinguished scholar, John Naisbett has worked in many
      different settings, including at the White House under Lyndon B. Johnson. He
      spent many years at Harvard University, and is best known for introducing a
      quantitative analysis of the major trends affecting America. One of those, of
      course, was demographics. Another was the aging of the planet. Another was
      technology. He recently authored a new book, High Tech, High Touch. Home care has
      "high touch" down to a science: that's the kind of care for which home care is
      famous. It is also important, however, that we introduce technology. As
      technology changes and offers the ability to provide new and more efficient ways
      of providing care, we need to embrace that opportunity. History will record that
      20 years ago, a man named John Naisbett made a contribution which literally
      changed the world, with his book Megatrends. It changed the way that we think
      about the world. It changed the way that we think about ourselves. He delivered
      the following speech at the 2001 National Association for Home Care Annual
      Meeting.

PMID- 11957854
TI  - Information technology: beyond agency operations to total support.

PMID- 11957855
TI  - The trend toward electronic time and attendance sheets.
AB  - One way in which savvy agencies can generate businesslike efficiencies is by
      using advanced electronic, telephone-based time, attendance, and data collection
      systems. Telephony solutions are helping agencies achieve cost and operational
      efficiencies, while assuring high standards of patient care.

PMID- 11957856
TI  - Update on Revised Patient Abuse Protection Act (S.1054).

PMID- 11957857
TI  - Health care trademarks: protecting valuable assets.

PMID- 11957858
TI  - NAHC Board of Directors sets association's legislative marching orders.

PMID- 11957859
TI  - Collaboration with your State's Hospital Association: surveying patient
      satisfaction across the continuum of care.

PMID- 11957860
TI  - State budget deficits creating crisis and opportunity for home care.

PMID- 11957861
TI  - Adapting to the new millennium: nursing licensure and home care.
AB  - To realize the promise of telemedicine and telehealth, state and federal
      policymakers must examine how licensure laws should be adapted to address remote
      care. While many projects are confined to the boundaries of a single state,
      specialized telemedicine, telehealth and e-health programs are being developed
      and implemented that transcend state boundaries.

PMID- 11957862
TI  - JCAHO working to effect change through public policy initiatives.

PMID- 11957863
TI  - Preventing ventilator-related deaths and injuries.

PMID- 11957864
TI  - JCAHO partners to develop pain management measures.

PMID- 11957865
TI  - Standards approved for Disease-Specific Care Program.

PMID- 11957866
TI  - Resident safety and health care error reduction standards.

PMID- 11957867
TI  - Care homes. Human toll behind the escalating closures.

PMID- 11957868
TI  - Domestic violence. Hitting home.

PMID- 11957869
TI  - Paediatric cardiac nursing. Call for new liaison posts.

PMID- 11957870
TI  - Children in care. System of care in need of a nursing check-up.

PMID- 11957871
TI  - Is bringing back matron just a publicity stunt?

PMID- 11957872
TI  - GPs: you're on your own.

PMID- 11957873
TI  - RCN in a spin over nurses' pay.

PMID- 11957874
TI  - Detecting depression.

PMID- 11957875
TI  - Mental health nurses are not medicalising misery.

PMID- 11957876
TI  - It's not always complementary.

PMID- 11957877
TI  - There's something about matron.

PMID- 11957878
TI  - Labour should listen to the people on personal care.

PMID- 11957879
TI  - Trying to keep it real.

PMID- 11957880
TI  - Fanfare for the common nurse.

PMID- 11957881
TI  - Strength through diversity.

PMID- 11957882
TI  - Classroom capers.

PMID- 11957883
TI  - It's time to wake the sleeping giant.

PMID- 11957884
TI  - The use of central venous catheters for i.v. therapy.

PMID- 11957885
TI  - Dementia care.

PMID- 11957886
TI  - Psoriasis: the role of the genetic research nurse.

PMID- 11957887
TI  - Unearthing evidence of clinical effectiveness.

PMID- 11957888
TI  - Union membership. RCN to check qualifications.

PMID- 11957889
TI  - Midwives to debate industrial action despite Milburn's 100m pounds sweetener.

PMID- 11957891
TI  - Fit for practice. Part 5.1: Accountability, autonomy and standards.

PMID- 11957890
TI  - Systems and diseases. Exploring normal anatomy and physiology. Nervous system. 9.
      Multiple sclerosis.

PMID- 11957892
TI  - Delivering change.

PMID- 11957893
TI  - Organ retention. Relatives still waiting.

PMID- 11957894
TI  - Hospital hygiene. Wards dirty say nine out of 10.

PMID- 11957895
TI  - Bullying. Hospice boss investigated after claims.

PMID- 11957896
TI  - Conservative party. Junior medics to learn from nurses.

PMID- 11957898
TI  - Asylum seekers' health. Access denied.

PMID- 11957897
TI  - Health manifesto. Lib Dems pledge more training, pay and beds.

PMID- 11957899
TI  - Rehabilitation services. A head start in recovery.

PMID- 11957900
TI  - Black mark for sexual health.

PMID- 11957901
TI  - Does clinical governance make any difference to patient care?

PMID- 11957902
TI  - Shut up and talk to me.

PMID- 11957903
TI  - The quiet revolution.

PMID- 11957904
TI  - Do we really need matron to mop up our mess?

PMID- 11957905
TI  - Don't knock nursing home staff.

PMID- 11957906
TI  - Meddling matrons are a mistake.

PMID- 11957907
TI  - Cooperation is core to care services.

PMID- 11957908
TI  - Private sector care a notch above the NHS.

PMID- 11957909
TI  - A pension worth working for.

PMID- 11957910
TI  - Putting the heart in state of the art.

PMID- 11957911
TI  - The NHS Plan. Cash with conditions.

PMID- 11957912
TI  - Early learning's a must in elderly care.

PMID- 11957913
TI  - Young's therapy for clients with personality disorders.

PMID- 11957914
TI  - A framework for telephone nursing.

PMID- 11957915
TI  - Larva therapy.

PMID- 11957916
TI  - Using larva therapy to debride an ischaemic toe.

PMID- 11957917
TI  - Staff screening. Random drug tests ruled out.

PMID- 11957918
TI  - Stoma care--3. Changing a 1-piece appliance.

PMID- 11957919
TI  - Fit for practice. Part 4.2: Improving quality.

PMID- 11957920
TI  - Nurses must get passionate about nutrition.

PMID- 11957921
TI  - Drug administration via a nasogastric tube.

PMID- 11957922
TI  - Developing an enteral feeding skills station.

PMID- 11957923
TI  - Increasing fibre: why and how.

PMID- 11957925
TI  - Primary care. Call to ban HCAs from taking blood.

PMID- 11957924
TI  - Lessons to be learnt.

PMID- 11957926
TI  - Feeding problems in elderly patients.

PMID- 11957927
TI  - Dutch euthanasia law. Nurses demand right to opt out of mercy killings.

PMID- 11957928
TI  - How the BBA helped agencies get referrals. Do hospitalized patients know your
      agency exists?

PMID- 11957929
TI  - How using social work can save money under PPS.
AB  - PPS calls for every employee to work efficiently together to assure success. This
      article outlines the various ways social work services can be used to benefit
      patient care and agency financial and organizational goals. It is a "must read"
      for clinicians, managers, and administrators to learn more about how social
      workers can play an increasingly important role in all aspects of the
      organization.

PMID- 11957931
TI  - Avoiding random acts of violence. Interview by Kathy Sitzman.

PMID- 11957930
TI  - Recovery from coronary artery bypass grafting at home: is your nursing practice
      current?
AB  - This article provides a comprehensive approach to caring for the patient who has
      experienced coronary artery bypass grafting and is recovering at home. Using the
      National Nursing Practice Guidelines for the Cardiac Home Care Patient as a
      guide, specific assessment guidelines and nursing interventions are discussed.

PMID- 11957932
TI  - Codependence. Is it a home healthcare concern?
AB  - Professional nurses have often been labeled as codependent with the implication
      that this is a negative attribute that compromises patient care and weakens
      boundaries. This intriguing article examines this concept relative to home care
      nurses and provides insight on how this issue affects their practice.

PMID- 11957933
TI  - A tool to measure nurse efficiency and value.
AB  - Home care nurses who have multiple roles can increase their value by validating
      their contributions and work efficiency. This article presents a method for
      tracking nurse efficiency for those who are paid on an hourly basis, and provides
      a mechanism to document their contributions to the home care agency.

PMID- 11957934
TI  - PPS: same song, third verse.

PMID- 11957935
TI  - Children's health care. Educating adults. Interview by Helene Mulholland.

PMID- 11957936
TI  - Recruitment. Central casting.

PMID- 11957937
TI  - Abortion. Born in the USA.

PMID- 11957938
TI  - Information technology. Net gains for online nurses.

PMID- 11957939
TI  - Should preconception genetic screening be available to all?

PMID- 11957940
TI  - Image changes.

PMID- 11957944
TI  - Let patients have 40 winks--or at least 25.

PMID- 11957945
TI  - Long haul before NHS is shipshape after Bristol.

PMID- 11957946
TI  - How to handle complaints.

PMID- 11957947
TI  - A class act.

PMID- 11957948
TI  - Alleviate the paper weight.

PMID- 11957949
TI  - Understanding the MRSA experience.

PMID- 11957950
TI  - Wilson's disease: from the liver to the brain.

PMID- 11957952
TI  - Workshops add to psychosis service.

PMID- 11957953
TI  - Laughter can be the best medicine.

PMID- 11957954
TI  - Recordings or summaries of consultations for people with cancer.

PMID- 11957955
TI  - Recently several patients have been admitted to our surgical ward following a
      suicide attempt.

PMID- 11957956
TI  - Nervous system 12. The pathophysiology and management of epilepsy.

PMID- 11957957
TI  - Let's bring continence out into the open.

PMID- 11957958
TI  - A new perspective on an old problem.

PMID- 11957959
TI  - Stroke, catheters and constipation: action plans.

PMID- 11957960
TI  - Stroke and continence care.

PMID- 11957961
TI  - Disposable body-worn pads for incontinence.

PMID- 11957963
TI  - Abdominal massage for adults with learning disabilities.

PMID- 11957964
TI  - Parkinson's disease--continence management.

PMID- 11957966
TI  - Profile. The remote reformer [interview by Christine Hancock].

PMID- 11957967
TI  - Government. Alan's A-team.

PMID- 11957968
TI  - Profile. Picking and choosing [interview by Helene Mulholland].

PMID- 11957969
TI  - Stress. Sisters are doing it all themselves.

PMID- 11957970
TI  - Addiction. Clouding the issue.

PMID- 11957971
TI  - Will independent sector involvement destroy the NHS?

PMID- 11957972
TI  - Making a visible difference.

PMID- 11957973
TI  - Stop the insanity of outing nurse addresses.

PMID- 11957974
TI  - Competence is for the greater good.

PMID- 11957975
TI  - Weed is no stepping stone.

PMID- 11957976
TI  - Foreign nurses should be allowed career choices too.

PMID- 11957978
TI  - Why honeymoon-fresh vaginas are in vogue.

PMID- 11957977
TI  - Research is the new nursing ritual.

PMID- 11957980
TI  - Resuscitation. 'Robbed of a peaceful death'.

PMID- 11957979
TI  - Have you got the right stuff?

PMID- 11957981
TI  - Poverty and the health divide.

PMID- 11957982
TI  - Tracheostomy patient care.

PMID- 11957983
TI  - Risk management in mental health.

PMID- 11957985
TI  - Staff safety. Violent patients get the red card.

PMID- 11957984
TI  - Sex education for the boys.

PMID- 11957986
TI  - NT campaign. DoH forced to clarify clause.

PMID- 11957987
TI  - Critical incident management.

PMID- 11957988
TI  - Tamoxifen for early breast cancer.

PMID- 11957989
TI  - Oncology/haematology ward where several patients are taking part in drug trials.

PMID- 11957990
TI  - Blood transfusion--2.

PMID- 11957992
TI  - Nurses to prescribe over 200 drugs.

PMID- 11957991
TI  - Fit for practice. 6.4: Clinical audit.

PMID- 11957993
TI  - Nursing leadership. Hancock swaps RCN for ICN.

PMID- 11957994
TI  - Public-private partnerships. Unison ups the anti on privatisation.

PMID- 11957996
TI  - Prison nursing. Nurse hostages released unhurt.

PMID- 11957995
TI  - Termination of pregnancy. Dutch 'abortion ship' ignites row in Ireland.

PMID- 11957997
TI  - Maternity services. Cash spent on legal cases outstrips care.

PMID- 11957998
TI  - Overseas recruitment. UK named and shamed for poaching skilled staff.

PMID- 11957999
TI  - Clinical care. Ombudsman's report raps negligent nurses.

PMID- 11958000
TI  - Keynote speech. Fonda calls for 'nurse power'.

PMID- 11958001
TI  - Smoking cessation. Nurses encouraged to quit before they tackle smokers.

PMID- 11958002
TI  - HIV/AIDS. African epidemic 'wiping out' other health gains.

PMID- 11958003
TI  - Patient complaints. Satisfaction guaranteed.

PMID- 11958004
TI  - Staff safety. Blowing the whistle on violence.

PMID- 11958005
TI  - Disability. Hear no evil, see no evil.

PMID- 11958006
TI  - Recruitment and retention. Brake at the border.

PMID- 11958007
TI  - NHS24. A distinctly Scottish service is just one call away.

PMID- 11958009
TI  - The dilemma of limb salvage.

PMID- 11958008
TI  - Amputation. Time to limber up.

PMID- 11958010
TI  - Should late terminations for foetal abnormality be stopped?

PMID- 11958011
TI  - Mad about the girls.

PMID- 11958012
TI  - Bedside manner is on the line.

PMID- 11958013
TI  - Lament for dying skills.

PMID- 11958014
TI  - Riding shotgun in the community.

PMID- 11958016
TI  - A small nod is worth a thousand words.

PMID- 11958015
TI  - Traditional nursing in a modern environment.

PMID- 11958017
TI  - The essence of care.

PMID- 11958018
TI  - The courageous advocate.

PMID- 11958019
TI  - Care to take away.

PMID- 11958020
TI  - Dignity in dementia care.

PMID- 11958021
TI  - Signs of the times.

PMID- 11958022
TI  - New hospital. Just like starting over.

PMID- 11958023
TI  - Fight for long-term care while you can.

PMID- 11958024
TI  - Preparing the patient for tracheostomy tube removal.

PMID- 11958025
TI  - Seamless health and social care at a price.

PMID- 11958026
TI  - The role of infant feeding advisers.

PMID- 11958027
TI  - Vincristine fatalities: lessons to be learnt.

PMID- 11958028
TI  - Education. Free training for foreign students axed.

PMID- 11958029
TI  - Care of the elderly. Anger at 'blatant ageism' of private company.

PMID- 11958030
TI  - Hip protectors for preventing hip fractures in the elderly.

PMID- 11958031
TI  - Work in a busy anticoagulation department.

PMID- 11958032
TI  - Systems and diseases. Exploring normal anatomy and physiology. Nervous system 11:
      Brain tumours.

PMID- 11958034
TI  - Overseas recruitment. Filipino nurses flee 'oppressive' contracts.

PMID- 11958033
TI  - Fit for practice. 6.5: Feedback from patients.

PMID- 11958035
TI  - Non-invasive positive pressure ventilation.

PMID- 11958036
TI  - Tuberculosis returns.

PMID- 11958037
TI  - Developing local TB guidelines.

PMID- 11958038
TI  - Queen's speech. Lukewarm response to health care proposals.

PMID- 11958039
TI  - Expanding roles. Training is key to public confidence.

PMID- 11958040
TI  - Crime. 'Lazy' killer gets life.

PMID- 11958041
TI  - Staff safety. Attacks in London A&E up by 100%.

PMID- 11958043
TI  - Cardiac services. Heartening news for unit that was 'on its knees'.

PMID- 11958042
TI  - Occupational health. Court told overwork led to breakdown.

PMID- 11958044
TI  - Nurse-led services. GPs admit NHS direct is here to stay.

PMID- 11958045
TI  - Practice nursing. Numbers must double.

PMID- 11958047
TI  - Deacon gaffe embarrasses the Scottish executive.

PMID- 11958046
TI  - Anger over refusal to guarantee HV places on health boards.

PMID- 11958048
TI  - Public-private partnerships. Is health a private function?

PMID- 11958049
TI  - Racism. Resistance movement.

PMID- 11958050
TI  - Postnatal depression. The mother of all moods.

PMID- 11958051
TI  - This is our problem too.

PMID- 11958052
TI  - Are HCAs just 'wannabe' nurses?

PMID- 11958053
TI  - Are HCAs just 'wannabe' nurses?

PMID- 11958054
TI  - Should we stay or should we go?

PMID- 11958055
TI  - Red light for stalkers.

PMID- 11958056
TI  - There's more to nursing than the three Rs.

PMID- 11958057
TI  - Should health care assistants be working in critical care?

PMID- 11958058
TI  - No ad ban means more recruits to smoking.

PMID- 11958059
TI  - Can I combine nursing and the law?

PMID- 11958060
TI  - The natural way to go.

PMID- 11958061
TI  - Mental health. If you're happy and you know it.

PMID- 11958062
TI  - More haste, less speed in critical care.

PMID- 11958063
TI  - Critical care education is given a redesign.

PMID- 11958064
TI  - Making sense of arterial blood gases.

PMID- 11958065
TI  - The right plasma volume expander.

PMID- 11958066
TI  - Secondary care. Doctors fear staff exodus.

PMID- 11958068
TI  - NHS Direct. Appeals to A&E for advice have plummeted.

PMID- 11958067
TI  - Career patterns. Brain drain of senior nurses to NHS Direct.

PMID- 11958069
TI  - Hands-on detection of systemic circulatory deterioration.

PMID- 11958070
TI  - How to use nitrates.

PMID- 11958071
TI  - Systems for routine surveillance for people with diabetes mellitus.

PMID- 11958072
TI  - Man had several strokes and was not expected to survive the first 24 hours
      following admission.

PMID- 11958073
TI  - Blood transfusion--3.

PMID- 11958074
TI  - Fit for practice. 6.6: Clinical supervision [continuing education credit].

PMID- 11958075
TI  - Public Health. Teen ads team set for backlash.

PMID- 11958076
TI  - Insurance. Midwives could face subs rise.

PMID- 11958077
TI  - Care of the elderly 200 m pounds for personal care.

PMID- 11958079
TI  - Privatisation. Nurses escape private plans.

PMID- 11958078
TI  - Cancer care. Scottish clinicians take control of 40 m pounds cancer strategy.

PMID- 11958081
TI  - Racism. Expert doubts DoH ethnic target.

PMID- 11958082
TI  - Care of the elderly. Home bosses guilty of abuse.

PMID- 11958083
TI  - Litigation. School ruling could 'change world of nursing'.

PMID- 11958084
TI  - Compensation. Stress nurse 'shouldn't get a penny'.

PMID- 11958085
TI  - Stroke. One in five patients gets no specialist care.

PMID- 11958086
TI  - Coronary care. Public defibrillators save two lives.

PMID- 11958087
TI  - NHS Direct. Patients to be nursed via TV.

PMID- 11958088
TI  - Care homes. VAT decision adds 100 pounds a week to fees.

PMID- 11958089
TI  - Care of the elderly. 'Ageist' ban lifted.

PMID- 11958090
TI  - Pay. Nurses threaten to quit bank as rates are slashed.

PMID- 11958091
TI  - Privatisation. Yellow-brick road to nowhere.

PMID- 11958092
TI  - Child carers. On the shoulders of children.

PMID- 11958093
TI  - Reputations. Dimming the candle we hold for Florence.

PMID- 11958094
TI  - Is Britain ready for voluntary euthanasia?

PMID- 11958095
TI  - Great expectations.

PMID- 11958097
TI  - Am I doing a higher grade's work?

PMID- 11958098
TI  - Twinge benefits.

PMID- 11958099
TI  - Why getting nurses to use hoists is a long haul.

PMID- 11958100
TI  - Right is might.

PMID- 11958101
TI  - Pectus deformities: causes and effects.

PMID- 11958102
TI  - Prescribing for community nurses.

PMID- 11958104
TI  - Rewarding dementia nurses.

PMID- 11958106
TI  - A partnership scheme for adults with complex needs.

PMID- 11958105
TI  - When to use antihypertensives.

PMID- 11958107
TI  - Services for helping acute stroke patients avoid hospital admission.

PMID- 11958108
TI  - Orthopaedic nurse practitioner in a district general hospital. Finding it
      difficult to locate information on preassessment clinics in this specialty.

PMID- 11958109
TI  - Blood transfusion--4.

PMID- 11958110
TI  - Traumatic wounds: cleansing and dressing.

PMID- 11958111
TI  - Bandaging: a vital skill.

PMID- 11958114
TI  - Pain relief.

PMID- 11958116
TI  - Cinderellas are ready for the ball.

PMID- 11958115
TI  - Pressure ulcers: an assessment of the latest guidance.

PMID- 11958122
TI  - Homosexuality and the mental health professions. The impact of bias.

PMID- 11958123
TI  - [Application of quantum dot to life science].
AB  - As an eminent representation of nanotechnology, quantum dot (semiconductor
      nanocrystal) has caught great interests of scientists in physics, chemistry,
      material science, and biology extensively. Although its application to life
      science has just been explored, valuable progresses have been achieved in both
      biomacromolecule labeling and coding recently. The progress in quantum dot
      synthesis, its spectroscopic and photoelectronic properties, and its potential
      application to life science are reviewed.

PMID- 11958124
TI  - [Coexpression of caiB and caiE with two plasmids in E. coli].
AB  - Recombinant bacteria exhibiting high enzymatic activities were obtained by
      cloning and coexpression of both caiB gene and caiE gene in the host of E. coli
      Bl21(DE3), which encode carnitine dehydratase and a protein related to the
      synthesis of cofactor for carnitine dehydratase, respectively. In order to
      coexpress these two genes, compatible and incompatible two plasmids system were
      used, the difference between them was also studied. After induction with IPTG,
      both caiB and caiE genes were coexpressed in both compatible two plasmids system
      and incompatible two plasmids system. In the former system, the expressed
      products accounted for 17% and 10% of the total proteins in the host; in the
      later system, the proportion was 39% and 20%, respectively. The activity of
      carnitine dehydratase in E. coli Bl21(DE3) with either coexpression system is
      about 2.3 times than that in E. coli Bl21(DE3) with only pET28-caiB. The plasmids
      stabilities in these two systems were the same, all needed the help of antibiotic
      selective pressure.

PMID- 11958125
TI  - [Identification and tissue-specific expression of a full length cDNA encoding ZIP
      protein in Arabidopsis].
AB  - A full-length cDNA encoding a putative ZIP proteins, has been isolated from
      Arabidopsis cDNA library using a heterologous DNA probe. Sequence analysis showed
      that the deduced protein contained a leucine zipper and a possible nuclear
      localization signal domain. There was no identical proteins in the database we
      searched, but it shared high sequence homology with PNZIP from Pharbitis nil and
      two other open reading frames (ORF) of unknown function from Synechocystis spp
      and Porphyra purpurea. These together defined a new family of evolutionarily
      conserved leucine zipper proteins, which might play a role as a transcription
      factor in the regulation of gene expression. Southern and Northern blot analysis
      indicated that AT103 was a single copy gene and the accumulation of mRNA was
      obviously different in leaves, stems and roots in Arabidopsis.

PMID- 11958126
TI  - Detection of vitamin C-induced singlet oxygen formation in oxidized LDL using
      MCLA as a chemiluminescence probe.
AB  - In this study, it was observed that addition of vitamin C (vit C) to oxidized low
      density lipoprotein (Ox-LDL) by cupric ions (Cu2+) could result in the formation
      of singlet oxygen (1O2). In experiments, 1O2 was detected by chemiluminescence
      method using a Cypridina luciferin analog, 2-methyl-6-(p-methoxyphenyl)-3, 7
      dihydroimidazo [1, 2-a] pyrazin-3-one (MCLA), as a selective and sensitive
      chemiluminescence probe. Additional experimental evidence for the formation of
      1O2 came from the quenching effect of sodium azide (NaN3) on vit C-induced
      chemiluminescence in the reaction mixture of LDL-Cu(2+)-MCLA. Analysis based on
      the experimental results demonstrated the plausible reaction mechanism is that
      vit C first converts Cu2+ to its reduced state and vit C becomes vit C radical
      itself, thereby stimulating the formation of peroxyl and alkoxyl radicals, and
      bimolecular reaction of peroxyl radicals results in 1O2 production in the systems
      studied.

PMID- 11958127
TI  - [Two types of photoelectric differential responses of bacteriorhodopsin and their
      mechanisms].
AB  - Based on experimental measurement of the pulse response of the bacteriorhodopsin
      (BR) film photocell, the impact response function of the device is obtained by
      data fitting with MATLAB software. A simulation system is accordingly built with
      the SIMULINK module. The output response signals of the BR film photocell under
      different stepping incident light are calculated based on this simulation system.
      It is concluded that the differential response described before (which occurs in
      milliseconds to seconds, outputs a positive pulse when light is on, and outputs a
      negative pulse when light is off) was not the intrinsic property of the BR
      molecule, but was partially caused by the measuring circuit. The differential
      response caused by the intrinsic property of the BR molecule happened in
      microsecond time scale, and it produced a negative pulse when light is on and a
      positive pulse when light is off. The mechanisms of the two types of differential
      responses are discussed.

PMID- 11958128
TI  - Cyclin D1 polymorphism and the susceptibility to NPC using DHPLC.
AB  - Cyclin D1 is a key cell cycle regulator and a candidate proto-oncogene, whose
      deregulation has been implicated in pathogenesis of several types of cancers,
      including NPC. A common A/G polymorphism (A870G) in exon 4 of the cyclin D1 gene,
      CCND1, is associated with the presence of 2 distinct mRNA transcripts for this
      G1/S regulatory protein, and CCND1 genotype has been related to some phenotypes
      of several tumors. To investigate the influence of cyclin D1 genotypes on the
      genetic susceptibility in humans from Southern China to sporadic nasopharyngeal
      carcinoma, cyclin D1 genotyping was performed by denaturing high performance
      liquid chromatography (DHPLC) and DNA sequencing analysis of the PCR products
      from 84 NPC cases and 91 normal controls. Gene frequency distribution was tested
      by Hardy-Weinberg equilibrium and comparison of cyclin D1 gene frequencies
      between the patient and control groups was performed by chi 2 test. Results
      showed that in NPC patients, the AA genotype of CCND1 was significantly lower
      (20.24%) than in normal controls (38.46%), and the GG and AG genotypes (GG + AG)
      were significantly higher in NPC group than in the control group (chi 2 = 6.946,
      P corrected = 0.016, OR = 2.463, 95% CI = 1.249-4.859). These suggest that the
      A/G polymorphism of CCND1 was associated with the susceptibility to NPC, and the
      GG and AG genotypes in NPC patients were significantly higher than those in
      normal controls.

PMID- 11958129
TI  - [A novel model for visualization of tumor cell-induced angiogenesis in vivo].
AB  - The bladder transitional cell carcinoma cell line, BTT739 from the T739 mouse,
      was transfected with a plasmid that encoded an enhanced green fluorescence
      protein (GFP) and the cells stably expressing GFP were selected and subcloned. 1
      x 10(3)-1 x 10(4) GFP-labeled BTT739 cells were injected under the skin of ear of
      T739 mice. On day 2-5 post injection, the most interesting manifestations
      observed were the chemotaxis-like movement of the tumor cells toward the pre
      existing host vasculature, host vessel dilation and tortuosity and increased
      extravasation. On day 10 or later, the sprout from pre-existing host vasculature
      was observed. Once angiogenesis was triggered on, the tumor cells grew more
      rapidly and exhibited a specific growth pattern where tumor cells always
      associated with or surrounded the vessels. The newly formed microvessels always
      showed heavy extravasation. Immunohistochemistry staining revealed strong VEGF
      and VEGFR2 (Flk-1) expression in tumor cells. Angiography using Rhodamin-labeled
      dextran showed neovascularization with unprecedented clarity. However, the tumor
      mass, even bigger than 2 mm and being neovascularized, shrunk and then disappear
      in 3-5 days and left only delicated host vessels and recovered extravasation. The
      evidence from this observation indicated that angiogenesis induced by tumor cells
      after implantation into the host begins at very early stage. The micrometastases
      foci could not form or survive without vigorous and continuous angiogenesis.
      Furthermore, there was active VEGF paracrine and autocrine expression in tumor
      and high level VEGF secretion by tumor cells plays an important role in
      initiating angiogenesis and supporting micrometastases.

PMID- 11958130
TI  - [Cloning and sequence analysis of full-length trypsin cDNA of Culex pipiens
      pallens].
AB  - The expression difference of trypsin gene between deltamethrin-resistant strain
      and -susceptible strain of Culex pipiens pallens was further investigated, and
      the results showed that the expression of trypsin gene were respectively 4.3 and
      3.9 fold more in the resistant strain than in the susceptible strain, by reverse
      Northern blot and Northern blot assays. A full-length trypsin cDNA of 909 base
      pairs (GenBank/NCBI AY034060) with an open reading frame of 786 base pairs was
      cloned from the constructed cDNA library by the rapid amplification of cDNA ends,
      and the deduced protein of 261 amino acids was 55% homologous with Anopheles
      gambiae trypsin.

PMID- 11958131
TI  - [Expression of lecithin cholesterol acyltransferase and/or apoA-I mediated by
      recombinant adeno-associated virus in myogenic cells].
AB  - Lecithin cholesterol acyltransferase (LCAT) is the major enzyme producing most
      plasma cholesterol esters(CE) and a key participant in the process of reverse
      cholesterol transfer (RCT). The aim of this research is to co-express LCAT and
      it's natural activator apoA-I, with the recombinant adeno-associated virus
      vectors in the skeletal muscle cells, in order to pave a new way for gene therapy
      of the primary or secondary LCAT deficiency. 293T cells was cotransfected with
      pDG and rAAVAIL/rAAVL plasmids to produce infectious rAAV, and non-ionic
      iodixanol gradient centrifugation, followed by heparin affinity chromatography,
      were performed for separation, purification and concentration of rAAV. The
      particle numbers of rAAV, assayed by dot blot, were 7 x 10(14)/L (rAAVAIL) and 1
      x 10(14)/L (rAAVL). These vectors were then transduced into C2C12 myoblasts. The
      results of ELISA and Western blot for human apoA-I, and [3H]-cholesterol-labeled
      radiochemical methods for LCAT activity, showed that the expression of human apoA
      I cDNA and/or human LCAT cDNA in transduced C2C12 cells lasted for 30 days, even
      after myoblasts were differentiated into myotubes. PCR products for the transgene
      indicated the long-term persistence of transduced vector sequences. The results
      indicate that the methods used for production and purification of rAAV is
      efficient, and rAAV vector mediated the expression and secretion of LCAT and apoA
      I gene in C2C12 myoblasts successfully. It suggests that the use of rAAV vectors
      mediating the high efficiency, long-term expression of human LCAT cDNA and/or
      apoA-I cDNA in skeletal muscle in vivo can be a safe and fesible strategy for the
      gene therapy of LCAT deficiency.

PMID- 11958132
TI  - [Cloning, expression and characterization of human vascular endothelial growth
      factor receptor 1 tyrosine kinase].
AB  - Vascular endothelial growth factor receptor 1 (Flt1) plays an important role in
      angiogenesis. It was hypothesized that, upon binding to VEGF, Flt1 tyrosine
      kinase underwent dimerization and initiated the signal transduction in VEGF/VEGF
      receptor system. In this report, a soluble active Flt1 tyrosine kinase domain
      expressed in E. coli was obtained, and its properties were partly characterized.
      The cDNA of Flt1 tyrosine kinase domain was obtained from the total RNA extracted
      from human liver cancer tissues by using RT-PCR, and was cloned to vector pGEX
      KG. A soluble active GST-fusion protein of Flt1 tyrosine kinase domain (GST-F)
      was obtained from E. coli BL21 (DE3) pLysS. Although it was reported that GST-F
      contains no phosphorylation site, it did autophosphorylate in vitro. Mg2+ and
      Mn2+ were essential for the activity. It was also found that GST-F phosphorylated
      a synthesized substrate PolyE4Y, but not MBP and Src-related-peptide. The optimal
      Mg2+ and Mn2+ concentration for polyE4Y phosphorylation was 15 mmol/L and 0.5
      mmol/L, respectively. This work is helpful for developing the new anti-cancer
      drugs.

PMID- 11958133
TI  - [Effects of blastocyst surface oligosaccharide LeY on secretion and expression of
      matrix metalloproteinase in vivo].
AB  - The effects of oligosaccharide LeY on expression and secretion of matrix
      metalloproteinase (MMP) and tissue inhibitor of metalloproteinase 1 (TIMP1) of
      embryos were investigated in cultured mouse blastocysts by zymography, immuno-dot
      blots and RT-PCR after blocking the oligosaccharide on embryo surface with
      specific monoclonal antibody AH6. The cultured blastocysts were treated with
      antibody AH6 for 3 h, then the antibody was removed and culture was continued,
      and the expression and secretion of MMP and TIMP1 were analyzed at 1.5 h, 3 h and
      6 h. It was shown that, only 1.5 h after blocking, the expression of MMP2 gene
      and MMP9 gene in embryo was significantly declined, and expression of TIMP1 was
      slight increased, then secretions of MMP2, MMP9 were also declined at 3 h, but
      secretion of TIMP1 had no significant change during the period of observation.
      The results indicate that LeY may play a role of regulating the expression and
      secretion of MMP of mouse embryo at pre-implantation stage, by controlling the
      expression of MMP2 gene and MMP9 gene.

PMID- 11958134
TI  - [Differential proteomic analysis of human lung adenocarcinoma cell line A-549 and
      of normal cell line HBE].
AB  - To explore the differential proteomic expressions between human lung
      adenocarcinoma cell line A-549 and normal cell line HBE, a series of methods,
      including immobilized pH gradient-two dimensional polyacrylamide gel
      electrophoresis, silver staining, PDQuest 2-DE software analysis, peptide mass
      fingerprinting based on matrix-assisted laser desorption/ionization time of
      flight mass spectrometry (MALDI-TOF-MS) and SWISS-PROT database searching, were
      used to separate and identify the differential proteomic expressions between A
      549 and HBE. The results showed that the good 2-DE pattern including high
      resolution and reproducibility was obtained. After silver staining, the 2-DE
      image analysis by PDQuest 2-DE software detected average (890 +/- 38) spots in A
      549, and (757 +/- 27) spots in HBE. The average positional deviation of the
      matched spots between A-549 and HBE 2-DE maps was (2.85 +/- 0.48) mm in IEF
      direction, and (2.69 +/- 0.37) mm in SDS-PAGE direction. The differential
      proteomic expression analysis found that there were 535 matched spots between A
      549 and HBE 2-DE maps, 355 spots that were not matched in A-549, 222 spots that
      were not matched in HBE. 18 differential spots (8 spots in A-549 and 10 spots in
      HBE) were cut off from silver staining gel at random, digested in gel with TPCK
      trypsin, measured with MALDI-TOF-MS and searched in the SWISS-PROT database with
      PeptIdent software. 18 protein were preliminarily identified. These proteins were
      related to cell signal transduction, cell metabolism, proliferation and
      differentiation etc. There was a significant difference at protein level between
      human lung adenocarcinoma cell line A-549 and normal cell line HBE. It suggests
      that the differential expression analysis of proteomes may be useful to further
      study of the related proteins and the molecular markers of lung adenocarcinoma.

PMID- 11958135
TI  - [Site-directed mutagenesis of the cysteines of human IL-18 and its effect on IL
      18 activity].
AB  - To study the structure-function relationships of human IL-18(hIL-18), site
      directed mutagenesis was used to generate four hIL-18 cysteine mutants, C74S,
      C104S, C112S and C163S. The cDNAs of the four cysteine mutants were inserted into
      prokaryotic expression vector pJW2 and expressed as inclusion bodies in E. coli.
      The inclusion bodies were washed with 2 mol/L urea, dissolved in 8 mol/L urea,
      and purified by chromatography on Sephadex G-100 column. The purity of the
      purified mutants were greater than 90% as judged by SDS-PAGE. The activity of
      rhIL-18 C74S, C104S, C112S and C163S accounted for 5%, 81%, 58% and 11% of wild
      type, respectively. These results suggest that Cys74 and Cys163 play important
      roles in inducing IFN-gamma production in human peripheral blood mononuclear
      cells.

PMID- 11958136
TI  - Cloning, expression and purification of gussurobin, a thrombin-like enzyme from
      the snake venom of Gloydius ussuriensis.
AB  - Total RNAs were extracted from the venom gland of the snake Gloydius ussuriensis.
      The cDNA of gussurobin, a thrombin-like enzyme from Gloydius ussuriensis, was
      cloned and amplified by RT-PCR. Assay of the nucleotide sequence of the cDNA
      allowed postulation of the complete amino acid sequence for Gloydius ussuriensis,
      Chinese Viperdae. Its amino acid sequence exhibits significant homology with that
      of other snake thrombin-like enzymes. The cDNA of gussurobin was inserted into
      the vector pPIC 9K and expressed successfully in Pichia pastoris, strain GS115.
      The recombinant gussurobin was separated and purified from 500 ml culture and
      showed one band on SDS-PAGE.

PMID- 11958137
TI  - [Chinese little-fat-tail sheep prion protein gene belongs to PrPARH genotype].
AB  - The genomic DNA was extracted from lymphocytes of peripheral blood of Chinese
      little-fat-tail sheep. The prion protein gene(PrPc) was amplified by polymerase
      chain reaction. The PCR products were cloned into pUC19 plasmid and was
      sequenced. The results indicated that 771 bp amplified fragment contains the
      entire sheep PrPc coding sequence. There were 7 base pairs different with the
      reported sheep PrPc sequence, leading to three amino acids changes in the
      protein. It is show that its genotype is PrPARH, and these three polymorphisms
      may be linked to susceptibility or resistance to scrapie infection. Mature sheep
      prion protein gene was inserted into pET30a and expressed in E. coli, and 23 kD
      PrP25-231 protein was obtained. Recombinant PrP25-231 protein was purified by
      inclusion body washing, ion-exchange chromatography, reverse phase
      chromatography. Results of SDS-PAGE and Western blot showed that the purified
      PrP25-231 was obtained.

PMID- 11958138
TI  - [Influence of PKB on ROS regulation of proliferation in human 7721 hepatoma
      cells].
AB  - In the present study, the relationship between PKB signaling and reactive oxygen
      species (ROS) during the course of exogenous and endogenous ROS or antioxidants
      regulating human 7721 hepatoma cell proliferation was studied. To change
      endogenous ROS levels, 7721 cells were transfected with human manganese
      superoxide dismutase (MnSOD) construct containing sense or antisense MnSOD cDNA.
      Low level of exogenous ROS H2O2(1-10 mumol/L) significantly stimulated PKB
      activity and c-fos/c-jun expression and cell growth, which could be abolished by
      antioxidant danshensu (40 mg/L). It was observed that overexpression of MnSOD
      inhibited 7721 cell growth by inhibiting PKB activity and c-fos/c-jun expression;
      the PKB activity and c-fos/c-jun expression, however, were stimulated by down
      regulated MnSOD expression. In addition, PKB-7721 cells (transfected with sense
      PKB cDNA) promoted c-fos/c-jun expression by stimulating PKB activity. These
      results suggest that the redox state stimulated hepatoma cell growth through PKB
      pathway, which modulates AP-1 expression.

PMID- 11958139
TI  - [In vitro transcription of inducible nod gene nodA].
AB  - We observed in vitro transcription of nodA, an inducible nod gene. Primer
      extension analysis of the transcripts showed there always existed a transcription
      product identical to that of its in vivo transcription, when 10 mumol/L
      naringening and NodD protein was added in the in vitro transcription system.
      Induced in vitro transcription of nodA gene suggests that in its in vivo
      transcription there may also exist a kind of physical interaction among NodD
      protein, inducer naringening and promoter of nodA gene.

PMID- 11958140
TI  - [Cloning and expression of Tachypleus tridentatus factor C].
AB  - Factor C is an endotoxin-sensitive, intracellular serine protease zymogen which
      initiates the coagulation cascade system in the horseshoe crab hemolymph. The
      special lipopolysaccharide (LPS) binding activation of FC makes it a potential
      drug for anti-LPS treatment and has a high commercial value. Based on the
      sequence of reported FC from Japan horseshoe crab, two pairs of primers were
      designed. The total RNA was extracted from amebocytes of Chinese Tachypleus
      tridentatus and the cDNA was separated into two parts and were cloned using RT
      PCR, respectively. FCs from different geographical areas showed high homology in
      sequence. The whole FC cDNA was cloned into pET-28a (+) containing T7 promoter
      and recombinant expression plasmid pET-FC was constructed. The recombinant
      plasmid was transformed into E. coli BL21 (DE3). Recombinant FC was expressed as
      inclusion body when the expression strain was induced with 1 mmol/L IPTG.
      Refolded recombinant FC was confirmed to be active by bacteriostatic assay in
      vitro. The results of Western blot also suggested the recombinant FC may be able
      to cleave itself partly and produced an extra immunoblot band.

PMID- 11958141
TI  - [Expression, purification and function of rice nonspecific lipid transfer
      protein].
AB  - Plant nonspecific lipid transfer protein(nsLTP) is a class of protein which has
      in vitro lipid transferring activity between biomembranes. In order to study the
      antimicrobial function of rice nonspecific lipid transfer protein, a gene LTP110
      encoding rice nsLTP was cloned into ThioFusion expression vector pET32a (+) and
      expressed in host strain Bl21(DE3)trxB-. After induction by IPTG at 30 degrees C
      for 5 h, the fusion protein thio-LTP110 was in large amount produced. The
      expressed protein was purified by Ni2(+)-chelating Sepharose fast flow column,
      then digested by enterokinase. By passing through nickel affinity column again,
      the cleavage product, LTP110, was obtained. CD spectrum scanning from 185 nm to
      250 nm showed that the recombinant protein LTP110 had similar secondary structure
      with the nsLTP purified from rice etiolated seedlings. Activity determination by
      fluorescent lipid P-96 showed that it had lipid binding activity. Microbial
      inhibition test results revealed that LTP110 deterred germination of the spores
      of rice pathogen P. oryzae, showing it might be involved in plant microbial
      resistance function. Therefore, it has the potential to be used in plant
      transgene engineering to improve plant resistance.

PMID- 11958142
TI  - [A evolutionary approach to identification of orthologous relationship across
      proteomes].
AB  - How to identify the true orthologous and paralogous relationships among protein
      families is still a key problem in genome annotation and comparative protemics.
      Here, a evolutionary approach to ascertainment of the orthologous relationships
      across the genomes is developed. Forty-four cases of protein families are used in
      the test for the evolutionary approach. Compared with the method of COG (cluster
      of orthologous groups of proteins), this approach can generally identify the
      orthologous relationships and accurately predict the genome function.

PMID- 11958143
TI  - [Overexpression of EDAG-1 in NIH3T3 cells leads to malignant transformation].
AB  - To study the biological function of EDAG-1, a novel gene cloned by our lab
      recently, the EDAG-1 cDNA was subcloned into pcDNA3. 1(+) vector and transfected
      into NIH3T3 cells by Lipofect AMINE methods. Overexpression of EDAG-1 in NIH3T3
      cells resulted in loss of cell contact inhibition, anchorage-independent growth
      in soft agar and tumor formation in nude mice. These results suggest that EDAG-1
      is a transforming gene and may be associated with the development of tumors,
      especially in hematopoietic system.

PMID- 11958144
TI  - In vitro assembly of R-phycoerythrin from marine red alga Polysiphonia urceolata.
AB  - Scanning tunneling microscope was used to investigate the in vitro assembly of R
      phycoerythrin (R-PE) from the marine red alga Polysiphonia urceolata. The results
      showed that R-PE molecules assembled together by disc-to-disc while absorbing on
      HOPG surface, which just looked like the rods in the phycobilisomes. When the
      water-soluble R-PE was dissolved in 2% ethanol/water spreading solution, they
      could form monolayer film at the air/water interface. Similar disc-to-disc array
      of R-PE was constituted in the two-dimensional Langmuir-Blodgett film by the
      external force. It could be concluded that, apart from the key role of the linker
      polypeptides, the in vivo assembly of phycobiliproteins into phycobilisomes is
      also dependent on the endogenous properties of phycobiliprotein themselves.

PMID- 11958146
TI  - Proceedings of the Third Alghero International Conference on Multiple Sclerosis:
      Pathogenesis, and Therapy. May 21-24, 2000. Alghero, Sardinia, Italy.

PMID- 11958145
TI  - Virus protein assembly in microgravity.
AB  - The coat of polyomavirus is composed of three proteins that can self-assemble to
      form an icosahedral capsid. VP1 represents 75% of the virus capsid protein and
      the VP1 capsomere subunits are capable of self assembly to form a capsid-like
      structure. Ground-based and orbiter studies were conducted with VP1 protein
      cloned in an expression vector and purified to provide ample quantities for
      capsomere-capsid assembly. Flight studies were conducted on STS-37 on April 5-9,
      1991. Assembly initiated when a VP1 protein solution was interfaced with a Ca+2
      buffer solution (pH 5.0). After four days a second alignment terminated the
      assembly process and allowed for glutaraldehyde fixation. Flight and ground-based
      samples were analyzed by electron microscopy. Ground-based experiments revealed
      the assembly of VP1 into capsid-like structures and a heterogenous size array of
      capsomere subunits. Samples reacted in microgravity, however, showed capsomeres
      of a homogenous size, but lack of capsid-like assembly.

PMID- 11958148
TI  - Abstracts of Czech and Slovak Physiological Societies. February 7-9, 2001.

PMID- 11958147
TI  - Twenty-ninth Annual Conference on Yeasts organized by the Commission on Yeasts of
      the Czechoslovak Society for Microbiology. May 23-25, 2001. Smolenice, Slovakia.

PMID- 11958149
TI  - ECCO 11. Proceedings of the European Cancer Conference. Lisbon, Portugal, 21-25
      October 2001.

PMID- 11958150
TI  - Abstracts of the annual meeting of the Australasian Society for Infectious
      Diseases. Melbourne, Australia, 7-11 April 2001.

PMID- 11958152
TI  - Cordoba Biology Society XIII Annual Meeting. August 1-3, 2001, Cordoba,
      Argentina. Abstracts.

PMID- 11958151
TI  - Abstracts of the 16th meeting of the Clinical Cytometry Society. Clinical
      applications of cytometry. November 11-13, 2001. Orlando, Florida, USA.

PMID- 11958153
TI  - Argentine Society of Experimental Pharmacology XXXIII Annual Meeting. Corrientes,
      Argentina, November 14-16, 2001. Abstracts.

PMID- 11958154
TI  - Proceedings of the 1st International Meeting of the Congress on Nutrition and
      Athletic Performance. Edmonton, Alberta, Canada. August 8-11, 2001.

PMID- 11958155
TI  - Optimizing clinical benefits: shaping the future of renal aneamia with epoetin.
      The Third International Symposium on Anaemia Management and Research. April 5-8,
      2001. Paris, France.

PMID- 11958156
TI  - Gathering around grand midwife Mrs. Margaret Smith.

PMID- 11958157
TI  - Proceedings of the Fourth International Workshop on Monoclonal Antibodies Against
      Human Red Blood Cell and Related Antigens. Under the Aegis of the Institut
      National de la Transfusion Saguine and of the Etablissement Francais du Sang.
      July 19-20. Paris, France.

PMID- 11958158
TI  - Proceedings and Abstracts of the 44th Annual Thomas Petty Aspen Lung Conference.
      June 6-9, 2001. Aspen, Colorado, USA.

PMID- 11958159
TI  - ECG of the month. Reentry (echo, reciprocation).

PMID- 11958160
TI  - Echocardiogram of the month. Malignant melanoma.

PMID- 11958161
TI  - Bibliography. Current world literature.

PMID- 11958162
TI  - [Quality management and certification in oncology. Report from the DGHO Symposium
      at the DGHO annual meeting in Mannheim, 30 September 2001].

PMID- 11958163
TI  - [16th Congress of the German-Speaking Society of Intraocular Lens-Implantation
      and Refractive Surgery. 22-23 February 2002, Heidelberg, Germany. Abstracts].

PMID- 11958165
TI  - Practice guideline for the treatment of patients with bipolar disorder
      (revision).

PMID- 11958166
TI  - [Class 6 non-ionic dimer contrast media: high diagnostic sensitivity with proven
      tolerability in a wide range of indications. Satellite symposium of the 82nd
      German Radiology Conference. Wiesbaden, Germany, 25 May 2001].

PMID- 11958164
TI  - Abstracts from the American Association for Geriatric Psychiatry 15th Annual
      Meeting. February 24-27, 2002. Orlando, Florida, USA.

PMID- 11958168
TI  - [What caused blepharitis?].

PMID- 11958167
TI  - [Blue lips].

PMID- 11958169
TI  - Canadian Spine Society Lifetime Achievement Award.

PMID- 11958170
TI  - Canadian Spine Society 2nd Annual Meeting. Vernon, British Columbia, Canada.
      March 21-23, 2002. Abstracts.

PMID- 11958171
TI  - Collaborations must be developed.

PMID- 11958172
TI  - Alignment with basic sciences beneficial.

PMID- 11958174
TI  - Cumulative author, subject and title index volumes 100-125.

PMID- 11958173
TI  - A couple more thoughts...

PMID- 11958175
TI  - Abstracts of the American Spinal Injury Association 27th Annual Scientific
      Meeting. May 18-20, 2001, Long Beach, California, USA.

PMID- 11958176
TI  - Pressure ulcer prevention and treatment following spinal cord injury: a clinical
      practice guideline for health-care professionals.

PMID- 11958177
TI  - Abstracts of the 30th Annual International Neuropsychological Society Conference.
      February 13-16, 2002. Toronto, Ontario, Canada.

PMID- 11958178
TI  - From the Centers for Disease Control and Prevention. Chagas disease after organ
      transplantation--United States, 2001.

PMID- 11958179
TI  - From the Centers for Disease Control and Prevention. Progress toward tuberculosis
      control--India, 2001.

PMID- 11958181
TI  - From the Centers for Disease Control and Prevention. Manufacturer's recall of
      rapid assay kits based on false positive Cryptosporidium antigen tests-
      Wisconsin, 2001-2002.

PMID- 11958182
TI  - From the Centers for Disease Control and Prevention. Availability of continuing
      education CD-ROM program on strategies to increase adult vaccination rates.

PMID- 11958184
TI  - Public affairs update. 10 CFR Part 35 goes to Congress.

PMID- 11958185
TI  - Extra-intestinal pathogenic E coli.

PMID- 11958186
TI  - Pseudomigraine with prolonged aphasia in a child with cranial irradiation for
      medulloblastoma.
AB  - We report a 12-year-old child with episodes of migraine-like headaches with
      visual and motor auras a year after the surgical resection and radiation therapy
      for medulloblastoma The patient presented with an episode of headache, prolonged
      aphasia, right hemiparesis, status epilepticus, and salt wasting. There was no
      evidence of a structural lesion. The neurologic deficits resolved over a period
      of 6 weeks. Because of the progressive deterioration in neurologic deficits, the
      patient underwent an extensive battery of laboratory tests and multiple
      neuroimages, all of which were normal. The unusually prolonged neurologic deficit
      in this patient without demonstrable structural lesions and his eventual complete
      recovery were most likely caused by ischemia in the left hemisphere secondary to
      vasospasm. This presentation mimics migraine headache. Evidence suggesting that
      this represents a long-term complication of treatment of children with central
      nervous system neoplasia is presented.

PMID- 11958187
TI  - Society for Obstetric Anesthesia and Perinatology 34th Annual Meeting. May 1-5,
      2002, Hilton Head Island, South Carolina, USA. Abstracts.

PMID- 11958188
TI  - American Society for Artificial Internal Organs 48th annual conference. New York,
      USA, June 13-15, 2002. Abstracts.

PMID- 11958189
TI  - Canadian Ophthalmology Society and affiliated societies 2002 annual meeting. Hull
      Ottawa, Canada, 13-16 June 2002. Abstracts.

PMID- 11958190
TI  - Abstracts of the 75th Annual Meeting of the Japanese Pharmacological Society.
      March 13-15, 2002. Kumamoto, Japan.

PMID- 11958191
TI  - Associated Professional Sleep Societies 16th Annual Meeting. June 8-13, 2002.
      Seattle, Washington, USA. Abstracts.

PMID- 11958192
TI  - Abstracts of the 23rd Annual Meeting of the Society for Clinical Trials. May 12
      15, 2002, Arlington, Virginia, USA.

PMID- 11958193
TI  - Abstracts of the 78th Annual Meeting of the Physiological Society of Japan. March
      29-31, 2001, Kyoto, Japan.

PMID- 11958194
TI  - The rising generation: laying claim to the health of adolescents in English
      Canada, 1920-70.
AB  - During the opening years of "Canada's Century," adolescents came to constitute a
      "youth problem," another of the often-overlapping "social problems" of the day.
      Medical doctors formed a significant cohort among those authorized to identify
      such potential threats to the national health, in its every sense. As they
      successfully professionalized, modernized, and took the reins of a burgeoning
      child welfare movement, doctors became increasingly interested in adolescents.
      This essay considers the medicalization of adolescence in English Canada between
      1920 and 1970. During this half-century, doctors and other "experts" shaped and
      shared approaches to the all-encompassing "health" of the young, in collectively
      theorizing a modern adolescence.

PMID- 11958195
TI  - Complicating childhood: gender, ethnicity, and "disadvantage" within the New
      Zealand children's health camps movement.
AB  - By the mid-20th century New Zealand's children's health camps movement had gained
      the status of a national icon, highlighting children's health and well-being in a
      campaign unrivalled, before the 1960s, by any equivalent peace-time cause. The
      movement's long existence within a relatively small nation state with an
      increasingly vocal indigenous population makes it an ideal base from which to
      study challenges to the undifferentiated category of "the child." The success of
      the movement was based upon a highly unitary conception of childhood and an
      uncomplicated view of child health. The paper shows how at certain moments in the
      movement's development a blanket categorization of childhood was challenged,
      first by gender and later, and more substantially, by the ethnicity of health
      camp recruits. "Disadvantage" was a constant subtext, but its link with socio
      economic status was downplayed in official discourses. Gender was highlighted in
      the 1920s and 1930s when girls' health needs were informed by (White) racial
      anxieties. Thereafter the physical and mental health needs of boys underwrote
      health camp recruitment and programs, even if this was not formally acknowledged.
      From the late 1980s, however, gender was subordinated to ethnicity. A growing
      focus on the Treaty of Waitangi issues and relationships of Maori to social
      services saw Maori children become visible in New Zealand's health camps as never
      before. With an acknowledgement of difference came competition for funds and an
      undermining of the national consensus about child health.

PMID- 11958196
TI  - Designing for "the little convalescents": children's hospitals in Toronto and
      Montreal, 1875-2006.
AB  - This paper explores more than a century of changing ideas about the health of
      Canadian children through the architecture of pediatric hospitals in Montreal and
      Toronto. As a unique source in the history of medicine, hospital architecture
      reveals three distinct phases in the construction of children as patients. Early
      20th-century children's hospitals remained bastions of older spatial attitudes
      towards health. The postwar hospital was self-consciously modern, with an
      arrangement more scientific and institutional than its predecessor. Through
      reference to other typologies, the postmodern hospital marks a curious return to
      the earlier attitude that children's health is a family affair. Is the hospital a
      home for children or an institution for science?

PMID- 11958197
TI  - Alberta's provincial Travelling Clinic, 1924-42.
AB  - Providing health services to sparsely populated, geographically isolated areas
      was a major challenge in many Canadian provinces before the advent of universal
      hospital insurance in the late 1950s, and universal physician insurance in the
      late 1960s. The task was especially daunting during the interwar depression
      years. Nonetheless, from 1924 to 1942, Alberta's Department of Public Health
      sponsored an itinerant Travelling Clinic during the summer which conducted
      physical examinations, dental examinations and treatment, tonsillectomies and
      other minor surgery, and vaccination against smallpox to children in frontier
      areas of the province. This article analyses Alberta's Travelling Clinic from a
      public policy perspective and concludes that through the Travelling Clinic, the
      Alberta government provided a health service valued by many settlers at nominal
      cost to itself.

PMID- 11958198
TI  - Personal control and the ecology of community living settings: beyond living-unit
      size and type.
AB  - Personal control exercised by 74 adults from community living settings in
      Minnesota was evaluated. Comparisons between living-unit sizes or types
      controlled statistically for pre-existing differences in adaptive and challenging
      behavior. Individuals living semi-independently exercised more personal control
      than did residents of HCBS Waiver-funded settings, who had more personal control
      than persons from community ICFs/MR. Within the 1- to 5-person size range, size
      related differences were detected in personal control. Using hierarchical
      regression, we found that personal characteristics, self-determination
      competencies, and environmental variables all made significant, unique
      contributions to predicting personal control. Path analysis also revealed that
      this range of variables was related to personal control. These findings strongly
      support an ecological approach to self-determination.

PMID- 11958199
TI  - Cognitive deterioration in adults with Down syndrome: effects on the individual,
      caregivers, and service use.
AB  - Individuals with Down syndrome (N = 49) who had participated in serial
      neuropsychological assessments were assigned to one of three groups comparable in
      level of premorbid mental retardation: those showing cognitive deterioration,
      those comparable in age but not showing cognitive deterioration, and those not
      showing cognitive deterioration but younger. Those experiencing cognitive
      deterioration were less likely to receive day services, had more impoverished
      life experiences, and required more support compared to groups without cognitive
      deterioration. When age was controlled for, cognitive deterioration was
      significantly positively associated with caregiver difficulties and service use
      and negatively associated with life experiences for the individual. Results
      suggest a potential role for caregiver difficulties in influencing life
      experiences of adults with Down syndrome showing cognitive decline.

PMID- 11958200
TI  - Recognition of identity and expression in faces by children with Down syndrome.
AB  - The ability of three groups of children (with Down syndrome, age-matched with
      nonspecific developmental delay, and younger typically developing) to recognize
      identity and expression in adult faces was examined. In Experiment 1, the
      children with Down syndrome were equally proficient at recognizing unfamiliar
      faces when expression was varied but significantly poorer at recognizing
      expression overall, with a specific deficit in perceiving surprise and fear. In
      Experiment 2, using rotated faces, they were significantly worse at recognizing
      expression as well as at identifying known faces. These results, in conjunction
      with lack of any improvement with age, suggest that there is a specific deficit
      in processing facial expressions associated with Down syndrome, a finding
      consistent with the emerging picture of neurological disruption in this syndrome.

PMID- 11958201
TI  - Relinquishment of infants with Down syndrome in Israel: trends by time.
AB  - To assess factors affecting parental relinquishment of infants with Down
      syndrome, we conducted a nationwide cohort study of infants with Down syndrome
      who were born in Israel during 1979-1983 and 1987-1991. Overall relinquishment
      rate was 25%. Major factors affecting relinquishment were mother's age, birth
      order, infant's health status, and study periods. A decision to relinquish a
      newborn infant in the hospital is probably based on a combination of several
      parameters, such as the economic status of the family, social mores, and
      religious beliefs.

PMID- 11958202
TI  - Brothers and sisters of adults with mental retardation: gendered nature of the
      sibling relationship.
AB  - Differences and similarities between brothers and sisters of adults with mental
      retardation with respect to the instrumental (caregiving, companionship) and
      affective (positive affect, emotion) aspects of the sibling relationship were
      examined. Sisters scored higher than brothers in the caregiving, companionship,
      and positive affect aspects of the sibling relationship. Brothers' sibling
      relationships were conditioned by the gender of the sibling with mental
      retardation. Brothers of brothers with mental retardation had a more favorable
      emotional response than did brothers of sisters. Two-wave longitudinal data
      showed that sibling involvement and closeness increased over time, but was
      dependent upon changes in the health of the mother. The findings are discussed in
      relation to normative patterns in the sibling relationship across the life
      course.

PMID- 11958203
TI  - Behavior states and a half-full glass: a response to Mudford, Hogg, and Roberts.

PMID- 11958204
TI  - American Urogynecologic Society 20th Annual Meeting. October 14-16, 1999, San
      Diego, California, USA. Abstracts.

PMID- 11958205
TI  - Biological investigations of higher and lower plants aboard Soyuz 19.
AB  - Biological investigations carried out aboard Soyuz 19 consisted of three
      independent complex experiments. All biological materials aboard the spacecraft
      were kept in "Biocat" thermostats which maintained the required temperature. The
      objective of the experiment "Genetic investigations" was to determine the effect
      of space flight factors on the heredity of lower (Chlamydomonas reinhardi Dang)
      and higher (Crepis capillaris (L) Wallr and Arabidopsis thaliana (L) Heynh)
      plants, and on the radiosensitivity of plant seeds and the radiation effect of
      prior gamma-irradiation. The space flight factors decreased the survival of
      Chlamydomonas cells and A. thaliana plants of the first generation. They
      decreased the germination of seeds, increased the rate of chlorophyll mutations
      and embryonal lethals, produced no effect on the rate of visible mutations in
      unicellular algae, increased the rate of chromosome aberrations in root meristem
      cells C. capillaris, induced disturbances in mitosis of unicellular algae and
      modified the effect of prior gamma-irradiation. The experiment "Growth of micro
      organisms" was conducted with a culture of Proteus vulgaris in a growth chamber.
      After return to the laboratory the experimental and control variants were studied
      for twenty-two tests. The control and experimental material differed in the
      average cell size, biomass distribution, the character of haemotaxis, the rate of
      cell migration over the substratum surface, dehydrogenase activity, ribosomal
      aggregation, and ultrastructural peculiarities of cells. The experiment
      "Embryological investigations" was carried out to study the effect of space
      flight factors on embryogenesis of the bony fish Brachyodanio rerio. No
      abnormalities were noted in the course or rate of the development of spawn
      cultivated in a special thermostat.

PMID- 11958206
TI  - Summary of measurements of high-LET particle radiation in U.S. manned space
      missions.
AB  - A summary of measurements of high-LET particle radiation inside U.S. manned
      spacecraft is given for ASTP (Apollo Soyuz Test Project), Skylab and Apollo
      missions. The results include particle fluxes, integral LET spectra, and stopping
      density charge distributions derived from measurements made in plastic nuclear
      track detectors worn by astronauts and located at various positions inside
      spacecraft. The results presented for different missions cover a wide range of
      shielding depth and missions type.

PMID- 11958207
TI  - Comparison of the light-flash phenomena observed in space and in laboratory
      experiments.
AB  - Astronauts on Apollo and Skylab missions have reported observing a variety of
      visual phenomena when their eyes were closed and adapted to darkness. These
      observations were studied under controlled conditions during a number of sessions
      on board Apollo and Skylab spacecraft and the data available to date on these so
      called light flashes are in the form of descriptions of the phenomena and
      frequency of occurrence. Similar visual phenomena have been demonstrated in a
      number of laboratories by exposing the eyes of human subjects to beams of
      neutrons, alpha particles, pions and protons. More than one physical mechanism is
      involved in the laboratory and space phenomena. No direct comparison of the
      laboratory and space observations has been made by observers who have experienced
      both. However, the range of visual phenomena observed in the laboratory is
      consistent with the Apollo and Skylab observations. Measured detection
      efficiencies can be used to estimate the frequencies with which various phenomena
      would be observed if that subject was exposed to cosmic rays in space.

PMID- 11958208
TI  - Apollo-Soyuz light-flash observations.
AB  - While dark adapted, two Apollo-Soyuz astronauts saw eighty-two light flash events
      during a complete 51 degrees orbit which passed near the north magnetic pole and
      through the South Atlantic Anomaly. The frequency of events at the polar parts of
      the orbit is 25 times that noted in equatorial latitudes and no increased
      frequency was noted in the South Atlantic Anomaly at the 225-km altitude. The
      expected flux of heavy particles at the northern and southern points is 1-2 min-1
      per eye, and the efficiency for seeing HZE particles which were below the
      Cerenkov threshold is 50%.

PMID- 11958209
TI  - Biological effects of high-LET particles on corn-seed embryos in the Apollo-Soyuz
      Test Project--Biostack III experiment.
AB  - High-LET particle hits in embryos of Zea mays corn seeds, flown as part of
      Biostack III in the Apollo-Soyuz Test Project, were determined via plastic
      nuclear track detectors. Based on etched particle-track measurements, 41 embryos
      were hit in seed layer 1 which contained 80 seeds, and 49 hits occurred in layer
      2 which contained 79 seeds. The mean LET value and range of atomic numbers of
      recorded hits is, respectively, 210 +/- 57 keV micrometers -1 and 9 < or
      approximately Z < or approximately 26. Detailed analysis of one particular seed
      showing marked growth anomalies revealed two hits in the central region of the
      embryo. These two hits had LET values in the region of 100-150 keV micrometers-1,
      and Z > or approximately 20.

PMID- 11958210
TI  - Calculation of the radiobiological effects of heavy ions on eggs of Artemia
      salina flown in the Biostack experiments.
AB  - By factorizing fragmentation cross-sections of ions into a projectile and a
      target-depending part, their flux inside a space vehicle can be calculated. This
      factorization was found at Bevalac for high-energy oxygen and carbon ions. With
      some restrictions, an extension of the factorization law to heavier nuclei up to
      iron is indicated by cosmic-ray data. Using this factorization the known cross
      sections for the fragmentation of heavy ions (Z=6-26) in collisions with protons
      were extrapolated to heavier target nuclei and the energy spectra of nuclei of
      different charges in the interior of' the Biostack were calculated. The theory of
      Katz was applied to estimate the heavy-ion-induced radiation damage in Artemia
      salina. The results are compared with experiment.

PMID- 11958211
TI  - Preliminary results of the Biobloc experiment on the Cosmos 782 flight: effects
      of cosmic rays on brine shrimp eggs and tobacco seeds.
AB  - The aim of the Biobloc experiment is to determine the biological effects of
      cosmic rays. Biobloc is a stack made up of biological layers and physical
      detectors (nuclear emulsions and plastic). Artemia eggs and tobacco seeds are
      used by French workers. Irradiation by cosmic heavy ions induces a late
      developmental inhibition of Artemia eggs. A light increase of emergence rate is
      observed for the non-hit eggs. The results are compared with those of previous
      space experiments. Investigations on tobacco seeds are in progress.

PMID- 11958212
TI  - Response of cultured mammalian cells to accelerated krypton particles.
AB  - One of the more interesting observations made in early studies with heavy ions is
      that the cross-section of the radiosensitive area in mammalian cells increases
      with LET of HZE particles. It is not certain, however, whether this
      radiosensitive area is limited to the nuclear area of cells. The successful
      acceleration of krypton ions to 8.5 MeV/amu at the HILAC Lawrence Berkeley
      Laboratory, has provided an opportunity to gain more information on this
      question. Cultured human kidney cells (T-1), growing in exponential phase, were
      exposed to 3 MeV/amu krypton particles and their colony-forming ability studied.
      The survival curve was found to be exponential with a mean lethal dose D0=720
      rad. A calculation of the cross-section of the radio-sensitive area from the data
      obtained gives a value of about 145 micrometers2. Present results suggest that
      the inactivation cross-section stays about the same for heavy ions that have LET
      greater than 20,000 MeV cm2 g-1, that the nucleus is the only sensitive site for
      high LET radiation and that a single hit of a heavy ion with very high LET in the
      nuclear region of the cell can lead to lethal effects. Such particles are
      therefore extremely dangerous to proliferating living cells.

PMID- 11958213
TI  - Effects of radiation upon the light-sensing elements of the retina as
      characterized by scanning electron microscopy.
AB  - A model system using Necturus maculosus, the common mudpuppy, was established for
      evaluating effects of radiation upon the light-sensing elements of the retina.
      Accelerated heavy ions of helium and neon from the Berkeley Bevalac were used. A
      number of criteria were chosen to characterize radiation damage by observing
      morphological changes with the scanning electron microscope. The studies
      indicated retina sensitivity to high-LET (neon) particles at radiation levels
      below 10 rads (7 particles per visual element) whereas no significant effects
      were seen from fast helium ions below 50 rads.

PMID- 11958214
TI  - Metabolic energy requirements during manned orbital Skylab missions.
AB  - An investigation was undertaken to determine the metabolic cost of life in space.
      Energy intake was determined throughout the 28-, 59- and 84-day flights for each
      of the nine Skylab astronauts. Metabolic excretions were quantitatively collected
      and analyzed for a variety of biochemical constituents. Body mass was determined
      each day and body volume was ascertained by stereophotogrammetric means
      immediately pre- and post-flight. A ground-based control period of at least 3
      weeks preceded each flight, and one of at least 18 days followed each flight.
      Examination of the data reveals that all crew members lost mass in flight, and
      that this loss did not result in a net increase in density. Elevated urinary and
      blood nitrogen, a net negative calcium and nitrogen balance and a decrease in the
      radiographic density of certain bones support the conclusion that lean body mass
      decreased. That the loss was primarily proteinaceous in nature is evidenced by
      the comparatively small net change in total body water and by a decrease in total
      body potassium each measured by isotopic dilution techniques. These changes in
      body composition, despite a constant caloric intake in flight and on the ground,
      suggest that the body's demand for exogenous nutrient energy is not measurably
      changed by exposure to null gravity flight up to 84 days in duration.

PMID- 11958215
TI  - Skylab nutritional studies.
AB  - Precise nutritional specifications arising from both physiological and
      experimental requirements necessitated a comprehensive study of the chemical
      composition of the Skylab food supply. Each of the approximately seventy
      different food items was analyzed for digestible and non-digestible carbohydrate,
      and for protein, amino acids, fat, fatty acids, vitamins and minerals. Menus were
      formulated to provide at least the National Research Council's Recommended
      Dietary Allowance of all essential nutrients and, in addition, to provide
      constant daily intakes of calcium, phosphorus, magnesium, sodium, potassium and
      protein. In general, the crew members adhered to their programmed menus. The
      ability to swallow and digest food was unaffected by prolonged weightlessness.
      Taste acuity also appeared to be undiminished in flight. The bone and muscle
      changes which occurred in previous flights were more pronounced in Skylab. It is
      concluded that these changes did not develop as a result of nutritional deficit.
      If such changes are nutritionally related, they point to the existence of
      nutritional requirements in weightlessness which differ quantitatively from those
      observed on earth.

PMID- 11958216
TI  - Preliminary results of medical investigations during manned flights of the Salyut
      4 orbital station.
AB  - In 1975 the Soviet Union performed two manned flights on board the orbital
      station Salyut 4. The first mission of 30 days was flown by A. A. Gubarev
      (Commander) and G. M. Grechko (Flight Engineer) and the second mission of 63 days
      by P.I. Klimuk (Commander) and V.I. Sevastyanov (Flight Engineer). The present
      paper gives preliminary data on the general health and cardiovascular
      investigations of the crew members during and after flight. The clinical and
      physiological examinations of the cosmonauts showed that the work-rest cycles and
      counter-measures used helped to maintain their good health and high performance
      in flight, to alleviate adverse reactions and to facilitate readaptation post
      flight. Medical results of the post-flight investigations revealed no changes
      that may detract from further increasing the duration of manned space missions.

PMID- 11958217
TI  - Medically important micro-organisms recovered from Apollo-Soyuz Test Project
      (ASTP) crew members.
AB  - The possibility of significant alterations in the microbial populations
      inhabiting the integument and upper respiratory tract of space flight crew
      members has been proposed by various authors. The Apollo-Soyuz Test Project
      (ASTP), a unique space flight in which two teams of crew members from different
      geographical areas joined in space, presented an unusual opportunity to evaluate
      in-flight cross-contamination and other anomalous behavior of the microbial
      populations. Accordingly, the medically important microbes recovered from the
      five (3 USA and 2 USSR) ASTP crew members before and after flight were evaluated
      in relation to specific theoretical alterations. The phenomenon of
      "simplification", in which the number of different types of species is reduced
      during spaceflight, did not occur within the population of medically important
      micro-organisms. Spontaneous post-flight illness due to infectious agents
      ("Microbial Shock") was also absent. Intracrew transfer of pathogens was
      established, but intercrew transfer was absent. Dysbacteriosis, in which sampled
      areas are flooded with unusually large numbers of a single type of micro
      organism, was not demonstrated although there was a significant increase in the
      incidence of gram-negative rods in the oral cavities of the two cosmonauts. The
      importance of all of these and other observations of the medically important
      micro-organisms recovered from ASTP crew members are explored with respect to
      past and future space flights.

PMID- 11958219
TI  - Life sciences and space research volume XV. Proceedings of the Open Meeting of
      the Working Group on Space Biology of the Nineteenth Plenary Meeting of COSPAR,
      Philadelphia, Pennsylvania, USA, 8-19 June 1976.

PMID- 11958218
TI  - Detection of optical asymmetry in amino acids by gas chromatography for
      extraterrestrial space exploration: results of a new soil processing scheme with
      breadboard instrumentation.
AB  - The life-detection experiments of the Viking spacecraft are of an active biology
      type that will attempt to elicit metabolic responses from soil samples. Because
      bioresponses may be difficult to stimulate, it is desirable also to devise a
      purely chemical life-detection experiment. The unique chemical property of living
      systems on which such an experiment could be based is the optical activity of the
      amino acids that compose its protein. We have devised a new soil processing
      scheme which has been laboratory tested and for which we have built semi
      automated breadboard instrumentation. The system involves the operations of
      heating, filtering, evaporation, conversion of the isolated amino acids to
      volatile diastereomers, injection onto a gas chromatographic column, and
      detection using a flame ionization detector. The breadboard form of the soil
      processing scheme and instrumentation has been successfully end-to-end tested.

PMID- 11958223
TI  - Captain James Cook's antimony cup.
AB  - Medicinal cups made of pure antimony metal were once common but are now rare and
      only about ten have been described. An unusual cup which belonged to Captain
      James Cook, the explorer, which has not previously been reported in the medical
      literature is described here.

PMID- 11958224
TI  - [Did Georges Bizet die of a acute articular rheumatism?].
AB  - As perhaps in the case of Mozart (1) or Malher (2), Georges Bizet may have died
      of an acute articular rheumatism or of its consequences.

PMID- 11958225
TI  - Medicines in the correspondence of the Mozart family.
AB  - The most famous members of the Mozart family were musicians - not physicians. In
      spite of that, the family correspondence of the Mozarts contains much noteworthy
      information on 18th century medicine. It comes mainly from Leopold, the famous
      composer's father, which is why the vast majority of the medical data presented
      in the letters cannot be found in the popular editions of the correspondence. One
      of the medicine-related subjects usually omitted or presented briefly in such
      editions concerns the medicaments used in the Mozart family. Out of more than 100
      remedies mentioned in the correspondence the article's author chose and described
      a few that seem to have played a particularly significant role in the life of the
      Mozart family.

PMID- 11958226
TI  - The prescribing physicians and sick scholars of Oxford: Jeremiah Webbe's
      apothecarial notebook, 1653-54.
AB  - The prescription book of Jeremaih Webbe, apothecary, illuminates the medical
      practices of a number of Oxford physicians, including those of Thomas Willis,
      Francis Barkesdale, and William Conyers. It provides an indication of the nature
      of the illness present in Oxford, especially among the students of the
      University, in the years 1653 and 1654.

PMID- 11958227
TI  - Intrusion and internalisation of the devil: popular saints vs. the Fathers of the
      Church.
AB  - In early Christianity, and in the domain of Byzantium in particular, the devil's
      interference with man took two distinct forms which may be identified as
      "intrusion" and "internalisation". The intruding form of the devil was presented
      in the hagiographies of popular saints, while the internalisation form was
      presented and elaborated upon by the Fathers of the Church. Intrusion was the
      most striking and characteristic demonic interference with man. It was an
      invasion of the body by demons or impure spirits that took possession of the
      person and caused madness and other illnesses. The internalisation form of
      demonic interference was more subtle and sinister, and although it was not
      causing mental illness it was affecting the minds of people by inflaming passions
      and interfering with judgement, thus leading to erroneous actions, contrary to
      the commands of God. The two forms of demonic interference that were compatible
      one with the other and might coexist, emerged from the power of the devil.
      Intrusion was probably more appealing to and understood by the crowds of the
      peasants addressed by the popular saints while internalisation was better
      understood by the educated and the town people addressed by the Fathers of the
      Church. The two forms of demonic interference have had a lasting effect on
      religious and spiritual thought and practice till modern times.

PMID- 11958228
TI  - The 2002 Medicare+Choice plan lock-in: should it be delayed?

PMID- 11958229
TI  - Experiences of working-age adults in the individual insurance market: findings
      from The Commonwealth Fund 2001 Health Insurance Survey.

PMID- 11958230
TI  - Family law--contract--Supreme Court of New Jersey holds that preembryo
      disposition agreements are not binding when one party later objects.--J.B. v.
      M.B., No. A-9-00, 2001 WL 909294 (N.J. Aug. 14, 2001).

PMID- 11958231
TI  - Criminal procedure--substantive due process--D.C. Circuit holds that the
      government may forcibly treat incompetent criminal defendants with antipsychotic
      medication to render them competent to stand trial. --United States v. Weston,
      255 F.3d 873 (D.C. Cir. 2001), petition for cert. filed (U.S. Sept. 5, 2001) (No.
      01-6161).

PMID- 11958232
TI  - Patent law--claim construction--U.S. District Court for the District of
      Massachusetts finds conflict on Federal Circuit and holds that product-by-process
      claims are not limited by their process steps. -- Trustees of Columbia University
      v. Roche Diagnostics GmbH, 126 F. Supp. 2d 16 (D. Mass. 2000).

PMID- 11958233
TI  - DNA databases: when fear goes too far.

PMID- 11958234
TI  - What "choice" do they have?: protecting pregnant minors' reproductive rights
      using state constitutions.

PMID- 11958236
TI  - Smoking--the charade is over!

PMID- 11958235
TI  - Organ harvests from the legally incompetent: an argument against compelled
      altruism.
AB  - Organ transplants may offer the best hope of long term survival for individuals
      afflicted with certain cancers or other debilitating diseases. The hope that a
      transplant may inspire in an organ recipient should not, however, be the
      determinative factor when the proposed source of the organ is incompetent.
      Competent adults are not compelled to act altruistically by undergoing a surgical
      invasion for the benefit of third parties. Children and mentally incompetent
      adults should likewise be protected from such compelled altruism. Case by case
      adjudication of petitions to harvest organs from incompetents are inevitably
      driven by a concern for the recipient and an unwarranted deference to parental
      authority, and not by concerns for the autonomy and well being of the incompetent
      donor. This Note argues that organ harvests from legal incompetents should be
      statutorily prohibited.

PMID- 11958237
TI  - Medication update.

PMID- 11958238
TI  - Medicare coverage of smoking cessation.

PMID- 11958239
TI  - Treatment of latent tuberculosis infection in contacts of new tuberculosis cases
      in the United States.
AB  - BACKGROUND: Few data are available describing treatment completion rates among
      recently infected contacts of tuberculosis (TB) cases, a group at high risk for
      development of active TB. METHODS: Health department records were reviewed for
      all contacts of 360 culture-positive pulmonary TB cases reported from five health
      departments in the United States in 1996. RESULTS: Of 2,267 contacts who
      completed screening, 630 (28%) had newly documented positive skin tests (121 with
      skin test conversion). Treatment of latent TB infection was documented to have
      been recommended for 447 (71%). Among these, treatment was documented to be
      initiated for 398 (89%). Of these, 203 (51%) were documented to have completed a
      6-month course of treatment, and 78 (20%) received directly observed treatment.
      Treatment was recommended more often for contacts < 15 years of age, skin test
      converters, close contacts, and contacts of smear-positive cases. Treatment
      completion rates were higher for skin test converters. CONCLUSIONS: In this
      study, fewer than one third of all persons with newly documented positive skin
      tests detected during contact investigations were proven to have completed
      treatment. Achieving high rates of completion of therapy for latent TB infection
      in recently infected contacts of active cases of pulmonary TB is essential to
      maximize public health prevention efforts aimed at eliminating TB.

PMID- 11958240
TI  - Protease inhibitor combination therapy and decreased condom use among gay men.
AB  - BACKGROUND: The objective of the study was to determine whether treatment with
      protease inhibitors is associated with unprotected sexual behavior. METHODS: A
      total of 592 HIV-infected persons recruited from statewide public clinics in
      nonurban Alabama communities completed an assessment that, among other variables,
      elicited information on demographics, current sexual practices, health status,
      and medication use. Associations of treatment with protease inhibitors and high
      risk sexual behavior were estimated, adjusting for potential confounders.
      RESULTS: Treatment with protease inhibitors was not associated with whether a
      person was sexually active or with high-risk practices among sexually active
      heterosexual men and women. Among men who had sex with men, however, treatment
      with protease inhibitors was associated with never using condoms and with
      inconsistent use of condoms. CONCLUSIONS: Clinicians treating patients with
      protease inhibitors should consider providing risk-reduction counseling.

PMID- 11958241
TI  - Effects of changing health care financial policy on very low birthweight neonatal
      outcomes.
AB  - BACKGROUND: Our objective was to determine whether perinatal referral patterns
      and clinical outcomes for very low birthweight infants changed in relation to
      changing Medicaid financial policies in coastal South Carolina. METHODS: Referral
      patterns and outcome indicators for very low birthweight infants were compared
      during two periods in a cohort design. RESULTS: A total of 520 infants were
      identified over two funding periods. A decrease in the proportion of nonwhite
      very low birthweight infants was identified. There was an increase in very low
      birthweight infants with Medicaid funding born outside our level III center.
      CONCLUSIONS: Changes in financial public policy have been successful in the
      movement of low risk pregnancies into the private sector. However, an increased
      proportion of deliveries of very low birthweight infants occurred outside the
      level III center.

PMID- 11958242
TI  - Uterine rupture and dehiscence: ten-year review and case-control study.
AB  - BACKGROUND: Previous cesarean section, oxytocin administration, and fetal
      macrosomia increase the risk of uterine rupture or dehiscence (URD). METHODS: All
      25,718 deliveries at Riverside Regional Medical Center from January 1990 to June
      2000 were reviewed to describe complications and identify risk factors for URD.
      RESULTS: Eleven uterine ruptures and 10 dehiscences occurred during this period
      (0.08%). One maternal death (5%) and three neonatal deaths (14%) occurred. Other
      complications included intrapartum nonreassuring fetal status (67%), 5-minute
      Apgar score < 7 (52%), maternal blood transfusion (24%), neonatal hypoxic injury
      (14%), hysterectomy (14%), and endometritis (10%). Uterine rupture/dehiscence was
      independently associated with fetal weight > or = 4,000 g, nonreassuring fetal
      status, use of oxytocin, and previous cesarean delivery; internal fetal
      monitoring reduced the risk of URD. CONCLUSIONS: To reduce the risk of URD, a
      delivery plan should include assessment of cesarean history and fetal
      macrosomia,judicious use of oxytocin, and intrapartum monitoring for
      nonreassuring fetal status.

PMID- 11958243
TI  - Residents with disabilities: a national survey of directors of emergency medicine
      residency programs.
AB  - BACKGROUND: The Americans With Disabilities Act (ADA) has been in effect since
      1990. The present study shows response to this act for emergency medicine (EM)
      residents nationwide. METHODS: A total of 121 surveys were mailed to the
      directors of American College of Graduate Medical Education (ACGME)-approved
      residency programs. A definition of disability was provided, and a second mailing
      was sent to those not replying. RESULTS: Ninety-two program directors (76%)
      responded, representing 4,644 residents. Of these, 62 residents (1.3%) were
      reported as having a documented disability. Programs with a known disabled
      resident were significantly more likely to have available resources for
      assistance. Forty-seven (52%) of the program directors suspected a resident might
      have an undiagnosed disability, and 40 (85%) of these recommended testing or
      referral. CONCLUSIONS: There is a wide array of disabilities among EM residents.
      Available assistance varies. This may apply to other residencies as well.

PMID- 11958244
TI  - Injury during contact with horses: recent experience with 75 patients at a level
      I trauma center.
AB  - BACKGROUND: The objective of this study was to examine equine-related trauma at a
      trauma center servicing a region in which there is significant contact between
      horses and humans. METHODS: Data were collected on all patients admitted to the
      University of Kentucky Medical Center from January 1994 to December 1998 for
      treatment of horse-related injuries. RESULTS: Seventy-five patients were admitted
      to our center after injuries due to contact with horses (0.75% of all trauma
      admissions). There were 42 men (55%). The mean age was 37 years (range, 3 to 81
      years). The majority of patients (67/75) were injured during recreational
      activities, and most fell or were thrown (40/75). Only 14% of patients were
      wearing helmets. The most common injuries were extremity fractures and head
      injuries, but thoracic and abdominal injuries were not rare. Of the 75 patients,
      34 required surgery. Five patients (6.7%) died, all of head injury. During the
      study period, 11 people died in Kentucky due to contact with horses. CONCLUSIONS:
      Injury due to contact with horses is uncommon even at a center servicing a region
      with a large equine population. However, injuries are often serious and lead to
      significant morbidity and occasional mortality. Prevention of death from horse
      related trauma is synonymous with prevention of head injury.

PMID- 11958245
TI  - Psychiatric consultations in a southern university hospital.
AB  - BACKGROUND: Differences in psychiatric referral rates among demographic groups of
      general hospital patients between 1995 and 1998 in a southern university setting
      were studied. The contribution of suicide attempts to referral rates was
      assessed. METHODS: The study was done by analysis of hospital admission and
      psychiatric consultation data. RESULTS: Psychiatric consultations were done in
      844 (2%) of 41,681 admissions. Among patients without suicide attempts, those
      between ages 30 and 59, whites, and internal medicine admissions had higher
      referral rates. Age, race, and admitting service were independently associated
      with psychiatric referral rates. CONCLUSIONS: Findings support previous research
      showing that psychiatric referral depends on a variety of factors that may be
      patient-related, disease-related, and/or physician-related. Physicians'
      motivations to refer or not, organizational barriers or facilitators, disease
      related, and/or patient-related factors (eg, age and race) need to be assessed
      further as determinants for requesting psychiatric consultation.

PMID- 11958246
TI  - Invasive aspergillosis treated with adjunctive hyperbaric oxygenation: a
      retrospective clinical series at a single institution.
AB  - BACKGROUND: Invasive aspergillosis is the leading cause of early death in many
      transplant centers and has a major impact on the management of hematologic
      malignancies. The mortality rate with current therapy (amphotericin B and
      surgery) has remained unacceptably high. In vitro data along with a few case
      reports have suggested a potential benefit of hyperbaric oxygen (HBO). METHODS:
      We retrospectively studied all patients referred to our service when histologic
      specimens suggested invasive aspergillosis. Our main assessment of outcome was
      survival 3 months after initiation of HBO. RESULTS: Ten patients were included.
      All received adjunctive HBO along with the standard of care. Rhinosinusinal
      infection was the primary presentation. The most common underlying conditions
      were hematologic malignancies. Six patients were free of signs of infection 3
      months after the first HBO treatment. CONCLUSIONS: Adjunctive HBO appears to be a
      valuable tool in this devastating condition. Further studies are warranted to
      clarify its role.

PMID- 11958248
TI  - Metaplastic carcinoma in an ectopic breast.
AB  - We describe the case of an 81-year-old woman in whom a mass developed in the
      chest wall over 3 weeks. No previous mass in that area was reported. Physical
      examination was remarkable only for a 13 cm painless, purplish mass in the
      anterior chest wall. No masses were palpable in the anatomic breasts, and no
      lymphadenopathy was evident. Thoracoabdominal computed tomography showed a 3.5 x
      7.0 cm necrotic mass; underlying muscle invasion could not be excluded. Wide
      excision of the tumor and underlying fascia was done, and margins were clear.
      Pathology showed a metaplastic carcinoma without continuity with either anatomic
      breast. Adjuvant radiotherapy was initiated because of the tumor's high-grade
      features. Twenty-six months after resection and adjuvant treatment, the patient
      continues to be free of disease. Metaplastic carcinoma is an unusual pathologic
      finding in the anatomic breast. This is the first report of its occurrence in
      ectopic breast tissue.

PMID- 11958247
TI  - Effect of parental education on decision-making about neonatal circumcision.
AB  - BACKGROUND: We investigated the impact of unbiased, published, easily accessible
      brochures on the parental decision about circumcision. METHODS: A total of 190
      women who were delivered of healthy male infants at Memorial-Hermann Hospital and
      Woman's Hospital of Texas from December 1, 1999, to April 30, 2000, were asked to
      complete a brief demographic self-description and questionnaire regarding their
      attitudes and beliefs about circumcision. The most recent American Academy of
      Pediatrics (AAP) brochure about circumcision was then distributed, and subjects
      completed the questionnaire a second time after reading the brochure. RESULTS:
      Eighty-five percent of participants opted for circumcision. No woman altered her
      decision on the basis of information in the AAP brochure. Regardless of parental
      desire for circumcision, responses to all questions before and after distribution
      of the AAP brochure were highly correlated. Circumcision status of the father and
      the parents' education and age were significantly associated with the decision to
      circumcise. There was no significant association between this decision and
      marital status, race, or religion. CONCLUSIONS: Parental education about the
      medical indications and possible risks of circumcision has no impact on the
      decision-making process about neonatal circumcision.

PMID- 11958249
TI  - Transient hypothalamic hypothyroidism and diabetes insipidus after electrical
      injury.
AB  - Transient or permanent diabetes insipidus (DI) due to damage in vasopressinergic
      neurons--which may be hereditary or caused by head injury, brain surgery, tumors,
      granulomatous disorders, infections, vascular disorders, autoimmunity, and
      idiopathic causes--is not rare. Hypothalamic hypothyroidism is due to decreased
      thyrotropin-releasing hormone secretion and is seen rarely. We report a case of
      transient hypothalamic hypothyroidism and transient DI due to electrical injury.

PMID- 11958250
TI  - The H-index: a measure of ideal weight from height alone.

PMID- 11958251
TI  - Pituitary apoplexy after administration of heparin and isosorbide dinitrate.

PMID- 11958252
TI  - Direct-Sun column ozone retrieval by the ultraviolet multifilter rotating shadow
      band radiometer and comparison with those from Brewer and Dobson
      spectrophotometers.
AB  - A methodology for direct-Sun ozone retrieval using the ultraviolet multifilter
      rotating shadow-band radiometer (UV-MFRSR) is presented. Total vertical column
      ozone was retrieved in three stations: Mauna Loa, Hawaii, in the U.S., and
      Regina, Saskatchewan, and Toronto, Ontario, in Canada, from direct solar
      irradiances of the UV-MFRSR at 325-, 305-, 332-, and 311-nm channels (2-nm FWHM).
      The total uncertainty of ozone retrievals in this study is +/-2.0%. For Mauna Loa
      the mean ratios of the UV-MFRSR column ozone retrievals to the collocated Dobson
      and Brewer were 0.998 and 0.986 between May and September of 1999. The mean ratio
      of UV-MFRSR retrievals to the collocated Brewer retrievals was 1.012 in Toronto
      between April and August of 1999, and the mean ratio of retrievals of the UV
      MFRSR to the collocated Brewer was 0.988 in Regina between June and September of
      1999. Total vertical column ozone values for solar zenith angles of >70 degrees
      were not considered, because of the signal-to-noise ratio and the angular
      response of the instruments, and were not used in the evaluation. The advantages
      of total vertical column ozone retrieval using UV-MFRSR include relatively low
      cost, computer-controlled operation, automated calibration stability checks, and
      minimal maintenance. It allows for the real-time measurement of total vertical
      column ozone. The UV-MFRSR is being used at 28 sites across the United States and
      2 sites in Canada that form the U.S. Department of Agriculture UV-B Radiation
      Monitoring and Research Program. This constitutes a unique network of total
      vertical colunm ozone measurement.

PMID- 11958253
TI  - Discrete-ordinates solution of short-pulsed laser transport in two-dimensional
      turbid media.
AB  - The discrete-ordinates method is formulated to solve transient radiative transfer
      with the incorporation of a transient term in the transfer equation in two
      dimensional rectangular enclosures containing absorbing, emitting, and
      anisotropically scattering media subject to diffuse and/or collimated laser
      irradiation. The governing equations resulting from the discrete-ordinates
      discretization of the angular directions are further discretized in the spatial
      and the temporal domains by the finite-volume approach. The current formulation
      is suitable for solving transient laser transport in turbid media as well as for
      steady-state radiative transfer in many engineering problems. The method is
      applied to several example problems and compared with existing steady-state
      solutions and Monte Carlo transient solutions. Good agreement is found in all
      cases. Short-pulsed laser interaction and propagation in a turbid medium with
      high scattering albedo are studied. The imaging of an inhomogeneous zone inside a
      turbid medium is demonstrated.

PMID- 11958254
TI  - Three-dimensional behavior of apodized nontelecentric focusing systems.
AB  - The scalar field in the focal volume of nontelecentric apodized focusing systems
      cannot be accurately described by the Debye integral representation. By use of
      the Fresnel-Kirchhoff diffraction formula it is found that, if the aperture stop
      is axially displaced, the focal-volume structure is tuned. We analyze the
      influence of the apodizing function and find that, whereas axially superresolving
      pupil filters are highly sensitive to the focal-volume reshaping effect, axially
      apodizing filters are more inclined to the focal-shift effect.

PMID- 11958255
TI  - Distributed-feedback fiber laser sensor for simultaneous strain and temperature
      measurements operating in the radio-frequency domain.
AB  - Radio-frequency (rf) beat frequencies between two longitudinal modes and two
      polarization modes of a birefringent dual-longitudinal-mode moire distributed
      feedback fiber laser are employed to measure strain and temperature
      simultaneously. Operating entirely in the rf domain, this approach potentially
      allows one to employ low-cost and precise rf measuring techniques. A strain
      temperature cross sensitivity of the strain- and the thermo-optic coefficients,
      which can be neglected in wavelength-based grating sensors, has been observed.
      The achieved sensor accuracy was +/-15 microepsilon and +/-0.2 degrees C.

PMID- 11958256
TI  - Quasi-distributed fiber-optic strain sensor: principle and experiment.
AB  - Sensors capable of making distributed measurements allow for monitoring of the
      entire structure. Optical fiber sensors are especially attractive for this
      purpose, since they are geometrically versatile and can be readily integrated
      within various types of structure and material. Development and characteristics
      of a quasi-distributed intrinsic fiber-optic strain sensor based on white-light
      interferometry are described. The research presented here describes the
      development of a new optical fiber sensor system for measurement of structural
      strains based on double white-light interferometry. Individual segments of single
      mode optical fibers forming a common-path interferometer are linked in series,
      and a scanning white-light interferometer provides for distributed sensing of
      strain signals from various locations in the structure. The system is configured
      for automatic compensation of drift due to environmental effects, i.e.,
      temperature and vibration. Strain gauges were employed for comparison and
      verification of strain signals as measured by the new system. The experimental
      results demonstrate the linearity of the system and the capability for
      distributed sensing of strains.

PMID- 11958257
TI  - Magneto-optical visualization of metal-loss defects in a ferromagnetic plate:
      experimental verification of theoretical modeling.
AB  - Rare-earth iron garnet films with in-plane magnetic anisotropy grown on [111]
      oriented substrates are promising for the visualization of magnetic leakage
      fields in nondestructive evaluation. Such magneto-optical films have to be
      specifically engineered, and we give an example of this technology. To assess the
      validity and accuracy of finite-element calculations of a magnetization assembly
      combined with the physical modeling of the image formation, comparisons between
      calculated and experimentally obtained magneto-optical images of metal-loss
      defects have been made. A convincing quantitative agreement is demonstrated. It
      is shown that both physical and computer modeling techniques allow for a
      predictive engineering design of the prospective applications and provide greater
      insight into the method.

PMID- 11958258
TI  - Optical detection of small changes in refractive indices in water by single-beam
      scattering.
AB  - We studied forward-scattered laser light that is produced when the light strikes
      an abrupt interface (air bubble in water) and when it passes unimpeded through
      diffused water layers caused by temperature gradients. Measured intensities of
      the scattered light indicated patterns that are due to both geometrical and
      physical optics. Distribution of intensities within the scattered beam changed
      with the average vertical temperature gradient. Shifts in locations of
      intensities indicated small changes in the index of refraction in the diffused
      scattering case.

PMID- 11958259
TI  - Integrating-sphere system and method for absolute measurement of transmittance,
      reflectance, and absorptance of specular samples.
AB  - An integrating-sphere system has been designed and constructed for multiple
      optical properties measurement in the IR spectral range. In particular, for
      specular samples, the absolute transmittance and reflectance can be measured
      directly with high accuracy and the absorptance can be obtained from these by
      simple calculation. These properties are measured with a Fourier transform
      spectrophotometer for several samples of both opaque and transmitting materials.
      The expanded uncertainties of the measurements are shown to be less than 0.003
      (absolute) over most of the detector-limited working spectral range of 2 to 18
      microm. The sphere is manipulated by means of two rotation stages that enable the
      ports on the sphere to be rearranged in any orientation relative to the input
      beam. Although the sphere system is used for infrared spectral measurements, the
      measurement method, design principles, and features are generally applicable to
      other wavelengths as well.

PMID- 11958260
TI  - Mueller matrix error correction for a fringe-free interferometry system.
AB  - We present an automated surface profiling system based on a shearing
      interferometer, in which precise measurement of the polarization states
      eliminates fringe ambiguity. A full error correction based on Mueller matrices
      allows comparatively inaccurate but rapidly switchable liquid-crystal wave plates
      to be used, enabling unambiguous profile information to be obtained in real time.

PMID- 11958261
TI  - Phase-shifting interferometry immune to vibration.
AB  - A modification of phase-shifting interferometry is proposed for microsurface
      profiling of flat surfaces under vibrating conditions. With this technique the
      required phase shift, achieved by quarter-wave plates and polarizers, is free of
      errors associated with motion. A nearly common optical-path configuration is
      achieved, and the effect of environment is reduced. The effect of environment on
      the optical system is also studied. Moreover, the measurement of phase is
      instantaneous, which increases the versatility of this technique to measure
      vibrating objects. Experiments were carried out on a smooth mirror surface
      excited with high-frequency vibrations, and the technique was found to be immune
      to vibrations of both high and low frequency.

PMID- 11958262
TI  - Design of null lenses for testing of elliptical surfaces.
AB  - Null lenses are designed for testing the oblate elliptical surface that is the
      third mirror of the off-axis three-mirror anastigmatic camera used for remote
      sensing. Modifying the conventional autostigmatic and autocollimation types of
      null lenses yields a mixed-type design that has a small annular flat mirror and
      high sensitivity. Detailed analyses of the sensitivity of the mixed-type null
      lens system with changes in each surface parameter are described.

PMID- 11958263
TI  - On-line monitoring of one-step laser fabrication of micro-optical components.
AB  - The use of an on-line monitoring method based on photoelasticity techniques for
      the fabrication of micro-optical components by means of controlled laser heating
      is described. From this description it is possible to show in real time the
      mechanical stresses that form the microelement. A new parameter, stressed area,
      is introduced that quantifies the stresses of a microelement during its
      fabrication, facilitating a deeper understanding of the physical phenomena
      involved in the process as well as being a useful test of quality. It also
      permits the stress produced in the manufacturing process and the optical
      properties of the final microelement to be correlated. The results for several
      microlenses monitored with this technique are presented.

PMID- 11958265
TI  - Radiation from a nonisothermal spherical cavity: an exact solution.
AB  - A numerical solution is given for the radiation intensity from a spherical cavity
      whose spatial temperature and emissivity are both arbitrary. This simplifies and
      clarifies previous research. A numerical example with large axial temperature
      gradient is given, and it is suggested that this analysis could help establish
      the spherical cavity as a radiation standard.

PMID- 11958264
TI  - Optical design using computer graphics.
AB  - For decades the computer has been the primary tool used for optical design.
      Typical tasks include performing numerical calculations for ray tracing and
      analysis and rendering graphics for system drawings. As machines become faster
      with each new generation, the time needed for a particular design task has
      greatly reduced, allowing multiple assignments to be performed with little
      noticeable delay. This lets the designer modify a system and then immediately see
      the results rendered in graphics with a single motion. Such visual design methods
      are discussed here, where graphics of systems and plots relating to their
      performance are produced in real time, permitting the optical designer to design
      by pictures. Three examples are given: an educational tutorial for designing a
      simple microscope objective, an unobstructed reflective telescope composed of
      three spherical mirrors, and a modified Offner relay with an accessible pupil.

PMID- 11958266
TI  - Spectral noise due to sampling errors in Fourier-transform spectroscopy.
AB  - An assessment is made of the spectral noise in Fourier-transform spectroscopy
      caused by sampling errors in the interferogram acquisition. Numerical evaluations
      are performed in the case of the REFIR (radiation explorer in the far infrared)
      instrument developed for the measurement of the long-wavelength Earth emissions
      from satellite platforms. In this case the slow response of a room-temperature
      pyroelectric detector, the relatively short acquisition time, the broadband
      operation, and the wish for a relaxed requirement of the mirror drive accuracy
      make sampling error an important issue. Different sampling methods can be
      considered for reduction of the spectral noise induced by sampling errors. The
      effects of different sampling methods are quantified and discussed for the
      selection of the most-suitable option for this instrument. We find that only
      sampling methods that introduce some compensation (either analog or digital) of
      the frequency dependence of amplitude and phase components of the acquisition
      system responsivity provide satisfactory results. In particular, the equal time
      sampling followed by a digital filter and numerical resampling has been examined
      minutely with a simulation model used to perform sensitivity tests of the main
      parameters that characterize the procedure.

PMID- 11958268
TI  - Efficient evolutionary algorithm for the thin-film synthesis of inhomogeneous
      optical coatings.
AB  - We propose an efficient evolutionary approach for the thin-film synthesis of
      inhomogeneous optical coatings. The proposed approach consists of global and
      local strategies by integration of decreasing-based mutations and self-adaptive
      mutations by means of family competition and adaptive rules. Numerical results
      indicate that the proposed approach performs robustly and is competitive with
      other approaches. Our approach, although somewhat slower, is flexible and can
      easily be adopted to other application domains. Our approach is also able to
      generate homogeneous solutions with two materials available.

PMID- 11958267
TI  - Technique for narrow-band imaging in the far ultraviolet based on aberration
      corrected holographic gratings.
AB  - We have developed a new family of imaging spectrometer designs that combine the
      imaging power of two-element telescopes with the aberration control of first
      generation holographic gratings. The resulting optical designs provide high
      spatial resolution over modest fields of view at selectable wavelengths. These
      all-reflective designs are particularly suited for narrow-band imaging below 1050
      A, the wavelength below which there are no transmitting materials in the UV. We
      have developed designs to efficiently map the spatial distribution of UV-emitting
      material. This mapping capability is absent in current and future astronomical
      instruments but is crucial to the understanding of the nature of a variety of
      astrophysical phenomena. Although our examples focus on UV wavelengths, the
      design concept is applicable to any wavelength.

PMID- 11958269
TI  - Thermal-feedback-controlled coagulation of egg white by the CO2 laser.
AB  - Temperature feedback control during laser-assisted tissue coagulation was
      investigated and demonstrated with the egg-white model. We observed the dynamics
      of photothermal denaturation during CO2 laser irradiation by simultaneously
      controlling surface temperature and monitoring He-Ne laser transmission of egg
      white samples. Once a quasi-constant surface temperature was established,
      transmission of egg white tended to decrease linearly with time. Analysis of
      experimental data strongly suggested a first-order rate process. Since
      transmission was primarily affected by heat-induced increase in the scattering
      coefficient and depth of coagulation, we speculated that changes in transmission
      were reliable indicators of accumulating photothermal damage. Our experiments
      demonstrated that thermal feedback can effectively control or limit photothermal
      damage.

PMID- 11958270
TI  - Three-dimensional time-resolved optical tomography of a conical breast phantom.
AB  - A 32-channel time-resolved imaging device for medical optical tomography has been
      employed to evaluate a scheme for imaging the human female breast. The fully
      automated instrument and the reconstruction procedure have been tested on a
      conical phantom with tissue-equivalent optical properties. The imaging protocol
      has been designed to obviate compression of the breast and the need for coupling
      fluids. Images are generated from experimental data with an iterative
      reconstruction algorithm that employs a three-dimensional (3D) finite-element
      diffusion-based forward model. Embedded regions with twice the background optical
      properties are revealed in separate 3D absorption and scattering images of the
      phantom. The implications for 3D time-resolved optical tomography of the breast
      are discussed.

PMID- 11958271
TI  - Design of near-infrared imaging probe with the assistance of ultrasound
      localization.
AB  - A total of 364 optical source-detector pairs were deployed uniformly over a 9 cm
      x 9 cm probe area initially, and then the total pairs were reduced gradually to
      60 in experimental and simulation studies. For each source-detector
      configuration, three-dimensional (3-D) images of a 1-cm-diameter absorber of
      different contrasts were reconstructed from the measurements made with a
      frequency-domain system. The results have shown that more than 160 source
      detector pairs are needed to reconstruct the absorption coefficient to within 60%
      of the true value and appropriate spatial and contrast resolution. However, the
      error in target depth estimated from 3-D images was more than 1 cm in all source
      detector configurations. With the a priori target depth information provided by
      ultrasound, the accuracy of the reconstructed absorption coefficient was improved
      by 15% and 30% on average, and the beam width was improved by 24% and 41% on
      average for high- and low-contrast cases, respectively. The speed of
      reconstruction was improved by ten times on average.

PMID- 11958272
TI  - Cutaneous manifestations of systemic cryptococcosis in immunosupressed patients.
AB  - Since its discovery 100 years ago, the encapsulated yeast Cryptococcus neoformans
      has been implicated in systemic infections of many immunocompromised patients and
      has been a leading cause of morbidity and mortality in AIDS patients. Clinical
      symptoms are often initially subtle or lacking. Cutaneous involvement often
      carries a dismal prognosis as it is usually a sign of dissemination. However,
      lesions may develop before any systemic or constitutional symptomatology, and
      despite their non specific appearance, are easily accessible for scrapings,
      biopsies and cultures. A high index of suspicion is of utmost importance in high
      risk individuals to avoid delaying the diagnosis and treatment.

PMID- 11958273
TI  - The role of met-enkephalin in silent myocardial ischemia in diabetic patients.
AB  - Met-enkephalin plasma levels were evaluated in 20 cardioischemic diabetic
      patients. All the patients had ECG ischemic signs. Ten patients with diabetic
      autonomic neuropathy, experienced no pain during myocarial ischemia. Met
      enkephalin levels in the diabetic patients with silent myiocardial ischemia were
      significantly lower compared to those in the symptomatic patients. This
      demonstrates that the absence of myocardial ischemic pain in neuropathic diabetic
      patients is not accounted for by met-enkephalin action.

PMID- 11958274
TI  - The value of stress thallium-201 single photon emission CT imaging as a predictor
      of outcome and long-term prognosis after CABG.
AB  - This study examined the capability of rest-redistribution 201Tl single photon
      emission CT imaging (TSPECT) done shortly after coronary artery bypass grafting
      (CABG) to predict outcome and long- term prognosis. Results of TSPECT at 5.5+/
      0.7 (range 4 - 8) months postoperatively were correlated during a 4-year follow
      up period wit mortality, major surgical and nonsurgical cardiac events and
      cardiac event-free survival in 170 patients who underwent CABG. Ten (5.8%)
      patients died during follow-up: 4 had a documented cardiac death (all of them
      with large or moderate reversible filling defects). In the survivors, there were
      10 nonfatal myocardial infarctions and 11 revascularization interventions.
      Patients who eventually required and underwent revascularization procedures
      demonstrated large or moderate reversible filing defects, in contrast with those
      who had no need for an additional procedure (15.7% versus 2.5%, p < 0.001).
      Postoperative TSPECT carried out soon after CABG had definite prognostic value
      and should be performed routinely to help decide treatment protocol.

PMID- 11958275
TI  - Metabolic syndrome X: a comprehensive review of the pathophysiology and
      recommended therapy.
AB  - Diabetes mellitus is associated with a markedly increase prevalence of coronary
      artery disease, found to be as high as 55% (Lyons, 1993). The metabolic syndrome
      X, a multifaceted clinical entity produced by genetic, hormonal and lifestyle
      factors which occurs frequently in the general population, has been associated as
      an end point in patients with diabetes (Timar, Sestier et al., 2000). New data
      suggests that a clustering of truncal obesity, glucose intolerance or non-insulin
      dependent diabetes mellitus, dyslipidemia and essential hypertension are key
      components of this metabolic syndrome X (Timar, Sestier et al., 2000). In fact,
      the metabolic syndrome X has been shown to precede frank diabetes in a
      substantial number of patients; hence similar multiple cardiac risk factors will
      be found in this population. Thus, primary care providers should identify
      patients at an early stage so that appropriate treatment can be readily
      instituted. The goal of this review is to summarize criteria for diagnosis of
      patients with the metabolic syndrome X and therapeutic targets of each individual
      component is analyzed in a attempt to reduce cardiovascular events and improve
      clinical outcome based on the available clinical data.

PMID- 11958276
TI  - A case of papillary muscle rupture caused by acute myocardial infarction.
AB  - A 63-year-old female was admitted because of cardiogenic shock due to complete
      rupture of the posterior papillary muscle. The diagnosis was made by
      echocardiography. She was treated successfully by an emergency replacement of the
      mitral valve. Early diagnosis and surgical treatment are mandatory and life
      saving in the case of complete papillary muscle rupture.

PMID- 11958277
TI  - Fluoroquinolone concentrations in plasma, urine, and bile after oral
      administration in rats with renal failure: useful technique for long-term bile
      collection.
AB  - Using a previously reported technique for bile collection, we studied the
      pharmacokinetics of levofloxacin (LVFX) and grepafloxacin (GPFX) in normal rats
      and in animals with renal failure. Continuous bile drainage was performed using
      normal and renal-failure Wistar rats. Oral GPFX or LVFX (40 mg/Kg) was
      administered. The drug concentrations in plasma, urine, and bile were determined
      by high-performance liquid chromatography. The area under the blood concentration
      time curve (AUC) in each renal-failure rat was calculated. There were no
      significant differences in GPFX concentrations in the serum, urine, and bile
      between the renal-failure and normal rats, but the LVFX level in the urine of the
      renal-failure group was statistically significantly lower than in the normal
      group. The AUC of GPFX had an opposite correlation with the degree of renal
      failure, but that of LVFX was correlated.

PMID- 11958278
TI  - Cardiac pacing as emergency care for serious bradyarrhythmia with circulatory
      shock.
AB  - Three cases of bradyarrhythmia with serious illness of extracardiac organs are
      reported. Case 1 had sick sinus syndrome. He was admitted to our hospital
      complaining of syncope and developed apnea. Case 2 had complete atrioventricular
      block and serious hepatic failure in the hospital. Case 3 had paroxysmal
      atrioventricular block. He complained of syncope which followed convulsions.
      Their symptoms might be due to circulatory shock caused by a lazy lower pacemaker
      from the ventricle. Emergent temporary pacing successfully improved the
      extracardiac organ dysfunction. Although their bradyarrhythmias were transient,
      permanent pacemakers were implanted to inhibit the recurrence. A quick temporary
      pacing should be indicated in patients with critical bradyarrhythmia like our
      cases for survival.

PMID- 11958279
TI  - Autonomic nervous function in patients with peptic ulcer studied by spectral
      analysis of heart rate variability.
AB  - This study is intended to clarify the relationship between occurrence of peptic
      ulcer disease and dysfunction of the autonomic nervous system. We studied heart
      rate variability and assessed the circadian rhythm of autonomic nervous function
      in 20 patients with peptic ulcer (PU group) and 20 age-matched healthy controls
      (N group) using 24-hour Holter monitoring. Moreover, the relationship between
      gastric juice secretion and autonomic activity was examined under intravenous
      injection of insulin or butylscopolamine in adult mongrel dogs. High frequency
      spectral (HF) power, an indicator of parasympathetic tone, was increased markedly
      at night in the PU group. Low frequency spectral (LF) power, an indicator of
      sympathetic tone modified by vagal tone, was higher during the day than at night
      in the N group, whereas this normal circadian rhythm of LF power disappeared in
      11 cases (55%) in the PU group. In addition, the LF power was increased
      significantly at night (p<0.01) in the PU group. HF power and gastric juice
      secretion was increased by the administration of insulin. High sympatho-vagal
      tone at night may result in spasm of gastric arteries and excess secretion of
      gastric acid in the PU group. These results suggest that the nocturnal
      acceleration of LF, HF, and LF/HF is related to peptic ulcer diseases.

PMID- 11958280
TI  - The level and species of plasma non-esterified fatty acids are not related to
      elevated plasma apolipoprotein B levels in familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL), the leading cause of familial
      hyperlipidemia with premature coronary artery disease, has been associated with
      insulin resistance and elevated plasma levels of apolipoproten B (apoB) and non
      esterified fatty acids (NEFA). Becaus dietary fats affect plasma cholesterol
      levels, and specific saturated fatty acids (FA) are particularly potent
      stimulators in vitro of apoB secretio from hepatocytes, we hypothesized that FCHL
      patients would exhibit elevations in plasma levels of total FA or specific
      saturated species. Five families containing 12 FCHL subjects (5 adults, 7
      children and 8 normals (5 adults, 3 children) were assessed by dietary,
      anthropometric, and plasma measurements (glucose, insulin, lipoproteins, total
      NEFA, and specific FA types). After adjustment of the data for age, gender, and
      family affiliation, multivariate ANOVA indicated that FCHL was significantly
      associated with elevated plasma levels of apoB (p = 0.001) and insulin (p< 0.001)
      and increased body weight (p=0.043). Nevertheless, dietary intakes of total and
      saturated fat were comparable in the two groups, as were plasma levels of total
      NEFA and the major saturated species. In a study population possessing the
      salient features of FCHL, circulating total NEFA were not elevated, nor were
      specific saturated NEFA that had been associated with apoB oversecretion in
      vitro. Despite the speculated link between plasma FA and apoB overproduction in
      FCHL, our data suggest that other metabolic factors underlie this disease.

PMID- 11958281
TI  - Evaluation of the total health promotion plan in Japan, as related to health
      promotion effects and the prevention of lifestyle-related diseases.
AB  - The present study was undertaken to investigate whether health-promoting
      activities in Japan are useful for preventing the development of lifestyle
      related diseases and for promoting health. One thousand, one hundred and sixty
      seven Japanese workers were given a medical health check and had their maximum
      oxygen uptake measured according to the total health promotion plan (THP)
      protocol, which the Japanese Ministry of Health, Labor and Welfare is actively
      planning. Correlations between the maximum oxygen uptake and performance on
      health check items were statistically evaluated. The maximum oxygen uptake was
      positively correlated with the duration of a worker's ability to stand on one
      leg, and on the frequency with which they performed upper body weight lifting. In
      addition, the maximum oxygen uptake was negatively correlated with age, body
      weight, thickness of subcutaneous fat in the upper arms and shoulders, body fat
      ratios, body mass index (BMI), maximum and minimum blood pressures, resting heart
      rates, and total cholesterol levels. Moreover, the maximum oxygen uptake tended
      to be significantly higher in both male and female subjects who exercised
      regularly. It is suggested that maximum oxygen uptake and regular exercising play
      important roles in the inhibition of risk factors for ischemic heart diseases.
      Therefore, we believe the THP can play an important role in the primary
      prevention of lifestyle-related diseases. The purpose of the THP in Japan is to
      promote the achievement of healthy lifestyles in individual subjects, both from
      mental and physical perspectives. These results suggest that such efforts may
      help prevent the development of lifestyle-related diseases.

PMID- 11958282
TI  - Vagotomy reduces obesity in MSG-treated rats.
AB  - In order to study the role of vagus nerve activity at the onset of obesity
      induced by monosodium glutamate (MSG), 30-day-old MSG-rats were vagotomized or
      sham operated. Body weight and food intake were recorded until animals were 90
      days old and then sacrificed. Naso-anal length was recorded for all animals.
      Periepididymal and retroperitoneal fat pads were isolated and weighed. Reduction
      of body weight and naso-anal length were registered in 30-day-old MSG-rats.
      Obesity could also be observed, as increase of Lee index indicated. Results were
      most evident in 90-day-old MSG-rats. In both groups neither body weight gain nor
      food intake was changed by vagotomy. However, fat accumulation on tissues was
      reduced by vagotomy in MSG-rats. The results showed that MSG-obesity is not
      related to an increment in food intake behavior. Vagotonia might play a role at
      the onset of MSG-obesity.

PMID- 11958283
TI  - Suppression of type II collagen-induced arthritis by a new isocoumarin, NM-3.
AB  - The anti-arthritic effect of NM-3, a new isocoumarin, was examined using a type
      II collagen-induced arthritis model for human rheumatoid arthritis in DBA/1J
      mice. NM-3 by oral administration suppressed dose-dependently (2-20 mg/kg/day)
      not only macroscopic changes such as erythema and swelling of limbs but also
      histopathologic changes and radiographic changes such as bone lesions. The
      efficacy of NM-3 was greater than those of disease-modifying anti-rheumatoid
      drugs (DMARDs), auranofin (40 mg/kg/day) and bucillamine (10 mg/kg/day). NM-3
      failed to suppress carageenan-induced edema and to inhibit the activities of
      inflammation-related enzymes including cyclooxygenase-1 and -2, 5-lipoxygenase
      and phospholipase A2, suggesting that the mode of anti-arthritic action of NM-3
      may be different from those of non-steroidal anti-inflammatory agents (NSAIDs).
      Since NM-3 inhibits angiogenesis in a mouse dorsal air-sac model, the observed
      anti-arthritic effect of NM-3 might be partly attributed to the antiangiogenic
      activity. Thus, NM-3 is a potential orally active therapeutic agent for the
      treatment of human rheumatoid arthritis.

PMID- 11958284
TI  - Effect of prokinetic agents, cisapride and metoclopramide, on the bioavailability
      in humans and intestinal permeability in rats of ranitidine, and intestinal
      charcoal transit in rats.
AB  - To investigate the effect of two prokinetic drugs, cisapride and metoclopramide,
      on the bioavailability of drugs, a marker drug, ranitidine, was administered to
      healthy volunteers following pre-treatments with or without the prokinetic
      agents. Cisapride or metoclopramide HCl (a respective dose of 10 mg) was
      administered orally 30 min prior to an oral administration of ranitidine (300
      mg). Serum samples were collected for a 12 h period after the administration of
      ranitidine and the concentration of ranitidine was determined by an HPLC method.
      The bioavailability parameters of the groups with the prokinetic agent
      pretreatment were compared with those of the control group. In addition, the
      effects of these prokinetic drugs on the in vitro apparent permeability of
      ranitidine across the rat jejunum in the Ussing chamber, and on the in vivo
      intestinal transit of charcoal meals in rats were also examined. The Tmax of
      ranitidine in human subjects was shortened significantly by the either of the
      pretreatments (i.e., with cisapride and metoclopramide). The AUC(inf) of
      ranitidine in human subjects was also decreased significantly in the case of
      cisapride pretreatment. However, no changes were observed for the values of Cmax
      and T(1/2) by the pretreatments. Rat studies revealed that cisapride and
      metoclopramide had no influence on the in vitro permeability of ranitidine or the
      in vivo intestinal transit of charcoal meals. Therefore, these data indicated
      that the changes in the bioavailability parameters (i.e., Tmax and AUC(inf)) in
      humans are not related with the intestinal permeability or intestinal transit of
      ranitidine. The shortened Tmax of ranitidine appears to be due to accelerated
      gastric emptying of the drug. However, underlying mechanisms for the decreased
      AUC(inf) of ranitidine in the case of cisapride pretreatment are currently
      unclear.

PMID- 11958285
TI  - Cytochrome P450 modification by a new oxazine derivative with hypolipidemic
      activity.
AB  - Plasma lipoprotein levels, related to atheromatosis, are influenced by liver
      function. Microsomal enzyme inducers are reported to modify serum lipoproteins
      and triglycerides. In this study, the effects of subchronic and acute treatment
      of rats with 3-(4-biphenyl)-3-n-propoxy-octahydro-1,4-pyrido[2,1-c]oxazine, a
      novel compound with hypolipidemic and antioxidant activities, on rat hepatic
      microsomal protein and total cytochrome P450, as well as on p-nitrophenol
      hydroxylase (CYP2E) and erythromycin N-demethylase (CYP3A) activities are
      examined. The subchronic treatment had no significant effect on liver weight,
      microsomal protein and total cytochrome P450. The acute administration lowered
      considerably cytochrome P450 content. The metabolic activities of CYP2E1 and
      CYP3A1/2 were not altered by the subchronic treatment, but were notably decreased
      after the single administration of 3-(4-biphenyl)-3-n-propoxy-octahydro-1,4
      pyrido[2,1-c]oxazine. The inhibition of drug metabolism by 3-(4-biphenyl)-3-n
      propoxy-octahydro-1,4-pyrido[2,1-c]oxazine cannot be completely correlated with
      the modification of plasma cholesterol, triglycerides and LDL cholesterol,
      although published data connect microsomal enzyme induction with a decrease of
      these parameters. This discrepancy could be attributed to the different
      biochemical events involved in enzyme induction and inhibition.

PMID- 11958286
TI  - Pharmacokinetic changes of oral sulfamethoxazole in rabbits with diabetes
      mellitus induced by alloxan.
AB  - Because physiological changes occurring in diabetes mellitus patients could alter
      the pharmacokinetics of the drugs used to treat infectious diseases resulting
      from diabetic complications, the pharmacokinetics of sulfamethoxazole
      (sulfamethoxazole is usually used to treat secondary infectious diseases
      resulting from diabetic mellitus) were investigated after oral administration of
      the drug (50 mg/kg) to control rabbits and rabbits with acute (experiment was
      performed at fifth day after two consecutive days intravenous administration of
      alloxan) and chronic (experiment was performed at thirteenth day after first,
      second, sixth, and tenth days intravenous administration of alloxan) diabetes
      mellitus induced by alloxan. Impaired kidney and liver functions were observed in
      acute and chronic diabetes mellitus groups based on plasma chemistry data, and
      liver and kidney microscopy. After oral administration of sulfamethoxazole to
      acute and chronic groups, the plasma concentrations tended to be higher and this
      resulted in a significantly greater area under the plasma concentration-time
      curve from time zero to time infinity, AUC (6001 and 3867 compared with 1569
      microg h/ml). This could be due to significantly slower (2-3 times) renal
      clearance because of impaired kidney function. The effects of diabetes on the
      pharmacokinetics of oral sulfamethoxazole were more considerable in acute group;
      the AUC and the maximum plasma concentration were significantly greater and
      higher, respectively, than those in control and chronic groups. After oral
      administration, some pharmacokinetic parameters of sulfamethoxazole were
      significantly different in diabetes mellitus.

PMID- 11958287
TI  - Plasma levels of myeloperoxidase and elastase are differentially regulated by
      hemodialysis membranes and anticoagulants.
AB  - To examine effects of dialyzer membranes and anticoagulants on hemodialysis (HD)
      triggered neutrophil degranulation. We measured plasma myeloperoxidase (MPO) and
      elastase (ELT) by an enzyme-linked immunoabsorbent assay. During routine HD with
      a cuprophane membrane and high molecular weight (HMW) heparin, plasma MPO was
      rapidly upregulated to maximal levels within 15 min after starting extracorporeal
      circulation. In contrast, the level of plasma ELT gradually increased such that
      the highest level was achieved at the end of the procedure. When polysulfone and
      polymethylmethacrylate membranes were substituted for cuprophane, the rise in ELT
      was markedly suppressed. Polysulfone was also capable of reducing the MPO
      response, although the effect was less prominent than that for ELT. As for
      anticoagulants, nafamostat mesylate (NM) completely suppressed the rise in plasma
      MPO during HD with cuprophane. Low molecular weight (LMW) heparin also partially
      inhibited this response. In sharp contrast, there was no significant difference
      in the ELT response between nafamostat, HMW, and LMW heparins. Thus, NM maximally
      suppressed the rise of plasma MPO but had no effect on the ELT response. Our
      results suggest that neutrophil degranulation of MPO and ELT is differentially
      regulated during HD. Polysulfone and NM appear to maximally reduce excessive
      neutrophil activation.

PMID- 11958288
TI  - Plasma matrix metalloproteinase-9 (gelatinase B) in patients with hepatocellular
      carcinoma.
AB  - Increased plasma levels of matrix metalloproteinase (MMP)-9 have been shown in
      cancerous diseases including hepatocellular carcinoma (HCC). Our present aim was
      to examine whether the measurement of plasma MMP-9 concentration is clinically
      useful for assessing or monitoring HCC patients. We measured the plasma MMP-9
      concentrations in 47 HCC patients, and compared the results with the
      clinicopathologic features. The plasma MMP-9 levels in patients with HCC were
      significantly higher than those in the normal controls. The plasma levels of MMP
      9 were not related to the size of HCC tumor, the grade of histological
      differentiation and the serum alpha-fetoprotein level. The plasma levels of MMP-9
      were not significantly changed after the effective treatment of HCC tumors. In
      conclusion, the plasma MMP-9 test was of little value for assessing or monitoring
      HCC patients.

PMID- 11958289
TI  - Pharmacokinetic changes of intravenous tacrolimus in rats with uranyl nitrate
      induced acute renal failure.
AB  - Because the physiological changes that occur in patients with acute renal failure
      could alter the pharmacokinetics of the drugs, the pharmacokinetics of tacrolimus
      were investigated after 1-min intravenous administration of the drug (1 mg kg(
      1)) to control rats and rats with uranyl nitrate-induced acute renal failure
      (rats with U-ARF). The impaired kidney and hepatic functions were observed in
      rats with U-ARF on the basis of physiological parameters and by microscopy of the
      tissues. After intravenous infusion of tacrolimus, the total area under the blood
      concentration-time curve from time zero to time infinity was significantly
      greater in rats with U-ARF than that in control rats (35.8 versus 29.2 microg min
      mL(-1)) due to significantly slower total body clearance of tacrolimus (27.9
      versus 34.3 mL min(-1) kg(-1)), and this could be due to significantly slower
      nonrenal clearance (because of impaired hepatic function). The urinary excretion
      of unchanged tacrolimus was almost negligible for both groups of rats, therefore,
      effects of kidney impairment on the pharmacokinetics of tacrolimus seemed to be
      minor.

PMID- 11958290
TI  - The effects of midazolam and ketamine on D-tubocurarine-induced twitch depression
      in septic rat diaphragm.
AB  - The aim of this study was to elucidate the effects of midazolam and ketamine on
      neuromuscular blockade induced by non-depolarizing muscle relaxants (NDMRs) under
      the condition of sepsis induced by panperitonitis. A CLP operation (laparotomy,
      cecal ligation, and puncture of the cecum; septic group) or sham laparotomy (sham
      group) was performed on rats under O2-isoflurane anesthesia. At 18 hours after
      the operation, isometric twitch tensions of rat nerve-hemidiaphragm preparations
      elicited by indirect or direct stimulation at 0.1 Hz were measured. Midazolam
      enhanced the dTc (1 microM)-induced twitch depression (p < 0.05) at a high
      concentration (10 microM) in the septic group but not in the sham group. Ketamine
      enhanced the dTc (1 microM)-induced twitch depression in the sham group (p <
      0.01) but not in the septic group. Midazolam and ketamine had no effect on
      directly elicited twitch tensions in either group. The results indicate that
      sepsis facilitates the midazolam-induced enhancement of the neuromuscular
      blocking effect of dTc but, conversely, inhibits the ketamine-induced
      enhancement. Sepsis elicits manifold alterations in the influence of intravenous
      anesthetics and sedatives on NDMR-induced neuromuscular blockade.

PMID- 11958291
TI  - Enhancement by dimethyl sulfoxide of 1,25-dihydroxyvitamin D3-induced
      differentiation in human promyelocytic HL-60 leukemia cells requires dimethyl
      sulfoxide-induced G0/G1 arrest.
AB  - We investigated the induction of differentiation in human promyelocytic HL-60
      leukemia cells by a relatively low concentration of 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3). The cells were markedly induced to differentiate by combined
      treatment with reduced concentrations of dimethyl sulfoxide (DMSO) and
      1,25(OH)2D3, neither of which alone had much of an effect on differentiation. At
      48 hr post-treatment, a greater proportion of DMSO- and DMSO/1,25(OH)2D3-treated,
      but not 1,25(OH)2D3-treated, cells were in G0/G1 than untreated cells. Our study
      indicates that the synergistic effect of DMSO and 1,25(OH)2D3 on the induction of
      differentiation in HL-60 cells requires DMSO-induced G0/G1 arrest.

PMID- 11958292
TI  - Structural chemistry and biological activities of natural products from Chinese
      herbal medicines--part II.

PMID- 11958293
TI  - Identification of uncultured bacteria in human salivary calculus.

PMID- 11958294
TI  - Intracellular targets of antibacterial peptides.
AB  - The recent past witnessed a decrease in the number of new antibacterial compounds
      approved by the regulatory agencies and an almost complete lack of molecules
      killing bacteria by novel mechanisms of action. The broad spectrum antimicrobial
      agents currently on the market carry the potential, and indeed victims, of
      resistance developed against them. The need for new types of antimicrobial drugs
      coincides with the desire of developing lead molecules that act selectively on a
      single strain, or perhaps on a few closely related strains. Such selectivity
      would exclude the likelihood of the emergence of broad-range resistance.
      Intracellular bacterial targets most prevalently proteins needed for the life
      cycle of bacteria, carry the potential to be a resourceful target for a new
      family of antimicrobial compounds. Inhibition of proteinaceous functions requires
      stereospecificity, and a drug structurally similar to the target proteins
      themselves. Indeed, some antibacterial peptides show selective inhibition of
      intracellular targets. A few native peptides and their designed analogs appear to
      kill only a limited number of bacterial strains. Identification of the binding
      sites on the target proteins would allow the design of strain-specific
      antibacterial and antifungal peptides without the fear of development of common
      resistance to these agents.

PMID- 11958295
TI  - Ribosomally synthesized antibacterial peptides in Gram positive bacteria.
AB  - The emergence of multidrug-resistant pathogens that has caused a serious problem
      in hospitals worldwide, has intensified the search for novel drugs, in order to
      replace or to be used in complement with the existing antibiotics. In this
      connection much interest has been focused on a group of antimicrobial peptides,
      so-called bacteriocins. These antagonising peptides, which are gene-encoded in
      contrast to those made by multi-enzyme-complexes, share some common physico
      chemical properties, such as being small, cationic, amphiphilic and often being
      membrane active. However, they differ greatly from each other in their primary
      sequence and exhibit an impressively large inhibitory spectrum which covers
      almost all bacterial genera, including many important pathogens and food-spoilage
      bacteria. Many of these peptides are produced by lactic acid bacteria, organisms
      which have been used by man from ancient time in diverse fermentation processes,
      to improve and/or prolong self-life of many food and feed products. Numerous
      bacteriocins have been purified and characterised in great detail, both at
      biochemical and genetic levels. Still, novel bacteriocins with new properties are
      reported in an increasing number in recent years. In this review we will give a
      brief status quo of the present knowledge on bacteriocin research; thus different
      aspects such as their diversity in nature, biochemical properties, modes of
      action, biosynthesis and genetics will be treated.

PMID- 11958296
TI  - Molecular design of bioconjugated cell adhesion peptide with a water-soluble
      polymeric modifier for enhancement of antimetastatic effect.
AB  - The adhesive interaction of tumor cells with various components of the
      extracellular matrix (ECM), such as laminin and fibronectin appears to play a
      crucial role in tumor metastasis. It has been reported that adhesive peptides,
      such as Tyr-Ile-Gly-Ser-Arg (YIGSR) in laminin and Arg-Gly-Asp (RGD), inhibited
      adhesion and invasion of various tumor cells to ECM in vitro, and exhibited
      inhibitory effects on pulmonary metastasis of B16-BL6 melanoma cells in mice.
      However, large doses of these peptides were required for significant anti
      metastatic effects in vivo, probably due to their rapid degradation by various
      peptidases and their rapid excretion from the blood into the urine. To overcome
      these problems, the development of an appropriate drug delivery system (DDS) is
      required to improve in vivo stability and prolong plasma half-lives. Several
      strategies such as peptide-cyclization and D-amino acid substation have been
      reported to improve stability in blood by inhibiting enzymatic degradation.
      However, even these approaches have proven insufficient to overcome rapid renal
      clearance from the circulation. On the other hand, bioconjugation with water
      soluble polymeric modifiers could markedly prolong the plasma half-lives by not
      only increasing peptidase resistance but also impeding renal excretion. In
      addition, it is possible to strictly control the in vivo pharmacokinetics of a
      peptide by introducing functional molecules with targeting or slow release
      capacities to the polymeric modifier. In this review we demonstrate with
      reference to our recent studies that bioconjugation of adhesive peptides with the
      appropriate polymeric modifier can enhance antimetastatic activity and may
      facilitate therapeutic use.

PMID- 11958297
TI  - Tuberculosis drug targets.
AB  - Despite the availability of the BCG vaccine and chemotherapy, tuberculosis (TB)
      remains a leading infectious killer worldwide. The recent rise of TB and
      especially the alarming increase of drug-resistant TB call for urgent need to
      develop new anti-TB drugs. Lengthy chemotherapy and increasing emergence of drug
      resistant strains pose a significant problem for effective control. The need for
      a lengthy TB therapy is a consequence of the presence of persistent Mycobacterium
      tuberculosis, not effectively killed by current anti-TB agents. A list of new
      drug candidates along with proposed targets for intervention is described. Recent
      advances in the knowledge of the biology of the organism and the availability of
      the genome sequence provide a wide range of novel targets for drug design. Gene
      products involved in controlling vital aspects of mycobacterial metabolism,
      persistence, virulence and cell wall synthesis would be attractive targets. It is
      expected that the application of functional genomics tools, such as microarray
      and proteomics, in combination with modern approaches, such as structure-based
      drug design and combinatorial chemistry to biology-based targets, will lead to
      the development of new drugs that are not only active against drug-resistant TB
      but also can shorten the course of TB therapy.

PMID- 11958298
TI  - Aspartic proteinases in disease: a structural perspective.
AB  - The aspartic proteinases are a family of enzymes involved in a number of
      important biological processes. In animals the enzyme renin has a hypertensive
      action through its role in the renin-angiotensin system. The retroviral aspartic
      proteinases, such as the HIV proteinase, are essential for maturation of the
      virus particle and inhibitors have a proven therapeutic record in the treatment
      of AIDS. The lysosomal aspartic proteinase cathepsin D has been implicated in
      tumorigenesis and the stomach enzyme pepsin, which plays a major physiological
      role in hydrolysis of acid-denatured proteins, is responsible for much of the
      tissue damage in peptic ulcer disease. Since aspartic proteinases also play major
      roles in amyloid disease, malaria and common fungal infections such as
      candidiasis, inhibitors to these enzymes are much sought after as potential
      therapeutic agents. In all aspartic proteinases, the catalytic aspartate residues
      are involved in an intricate arrangement of hydrogen bonds involving a solvent
      molecule which is presumed to be water. The catalytic mechanism is thought to
      involve nucleophilic attack of the active site water molecule on the scissile
      bond carbonyl generating a tetrahedral gem-diol intermediate. The design of
      inhibitors generally involves the use of short oligopeptides containing a
      transition state analogue which mimic this tetrahedral intermediate. The
      application of structure-based drug design to members of the aspartic proteinase
      family is the main subject of this review.

PMID- 11958299
TI  - The central role played by peptides in the immune response and the design of
      peptide-based vaccines against infectious diseases and cancer.
AB  - Vaccines are one of the most cost effective methods of improving public health
      thereby increasing the quality of life. Prophylactic and therapeutic treatment by
      vaccines can prevent infectious diseases and some cancers and could also be used
      in the treatment of autoimmune disorders. An appreciation of this potential has
      resulted in a burgeoning literature which not only describes the scientific
      efforts being made into designing new and improved vaccines but also drives the
      efforts being made by public health organizations world-wide in delivering
      vaccines to the community. At the forefront of technologies being applied to the
      design of vaccines is the use of synthetic peptides; the chemical technologies
      used to assemble peptides have made great strides over the last decade and
      assembly of hi-fidelity peptides which can be of high molecular weight,
      multimeric or even branched is now almost routine. Together with the advances in
      peptide technology our understanding of the molecular events that are necessary
      to induce immune responses has also made great strides. The central role that
      peptides play in immune recognition is now recognised and rules are emerging that
      are being applied to the construction of peptide-based vaccines that, in the
      right context, can induce humoral (antibody) and cellular (cytotoxic and helper T
      cell) immune responses. Synthetic peptides are exquisitely placed to answer
      questions about immune recognition and along the way to provide us with new and
      improved vaccines.

PMID- 11958300
TI  - The systemic inflammatory response syndrome following cardiac surgery: different
      expression of proinflammatory cytokines and procalcitonin in patients with and
      without multiorgan dysfunctions.
AB  - Cardiopulmonary bypass is associated with an injury that may cause
      pathophysiological changes in the form of systemic inflammatory response syndrome
      (SIRS) or multiple organ dysfunction syndrome (MODS). In the present study, we
      investigated the inflammatory response of patients with multiple organ
      dysfunctions following open-heart surgery. Plasma levels of cytokines (IL-1beta,
      IL-6, IL-8, IL-18) and procalcitonin (PCT) were measured on the first four
      postoperative days in 12 adult male patients with SIRS and two or more organ
      dysfunctions after myocardial revascularization (MODS group), and 15 patients
      without organ dysfunctions (SIRS group). All cytokines (except IL-1beta) and PCT
      were significantly elevated in MODS patients, with peak values at the first two
      postoperative days. The results of our study show a different expression of
      members of the IL-1 family following extracorporeal circulation. For the first
      time, we can document that IL-18 is involved in the inflammatory response and the
      initiation of the MODS following cardiopulmonary bypass. In addition to APACHE-II
      score, PCT, IL-8, and IL-18 may be used as parameters for the prognosis of
      patients with organ dysfunctions after cardiac surgery. Furthermore, it must be
      noted that the duration of the surgical procedure is one of the most important
      factors for the initiation of the inflammatory response.

PMID- 11958301
TI  - Inflammatory mediator removal by zero-balance ultrafiltration during
      cardiopulmonary bypass.
AB  - The abnormal conditions to which blood is subjected during cardiopulmonary bypass
      (CPB) trigger an activation of the inflammatory response in all patients to
      varying degrees. Both complement activation and the release of cytokines
      characterize this response. Most inflammatory mediators have a molecular weight
      that is below the membrane pore size of commonly used ultrafilters, which should
      allow them to be freely filtered. However, some mediators have been shown to fail
      to cross through the membrane even though they are small enough to cross. The
      purpose of the present study was to determine whether certain inflammatory
      mediators could be removed by ultrafiltration when performed during the rewarming
      phase of CPB. Thirty adult patients undergoing a single, open-heart procedure
      were randomized to either control (no ultrafiltration) or to the zero-balance
      ultrafiltration (ZBUF) group. ZBUF was performed by removing 3 l/m2 blood using a
      65-kDa ultrafilter with 1.3-m2 surface area. A volume of a balanced salt
      crystalloid solution (Plasmalyte) equal to the filtered blood volume was given to
      replace the fluid removed. Patient data was taken before CPB (T1), immediately
      following CPB (T2), and 12 h following the procedure (T3). The average volume of
      filtrate removed during ZBUF was 6405 ml, which was analyzed for the presence of
      interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF-alpha), C3a, and C5a.
      The average concentrations of the mediators measured in the effluent were: IL-1,
      0.17 pg/ml; IL-6, 0.64 pg/ml; TNF-alpha, 1.25 ng/ml; C3a, 782.6 ng/ml; C5a, 25.6
      ng/ml. In every case except for IL-1, the amounts of mediators removed were
      significantly greater than zero. This study demonstrates that ultrafiltration is
      a strategy that can be used during CPB in the adult to remove significant amounts
      of inflammatory mediators.

PMID- 11958302
TI  - Levels of inflammatory markers in the blood processed by autotransfusion devices
      during cardiac surgery associated with cardiopulmonary bypass circuit.
AB  - Intraoperative blood salvage devices allowing a reinfusion of red blood cells
      (RBCs) after processing of shed blood and stagnant blood in the mediastinal
      cavity are more and more used to reduce homologous blood requirements in cardiac
      surgery with cardiopulmonary bypass (CPB). As the proinflammatory activity of the
      shed blood also contributes to morbidity during CPB, we conducted a prospective
      study in order to examine the quality of autologous blood before and after
      processing with five different devices [BRAT2, Sequestra, Compact Advanced, Cell
      Saver 5 (CS5), Continuous Autologous Transfusion System (CATS)]. All systems
      resulted in an excellent haemoconcentration, ranging from 53.7% (Compact) to
      68.9% (CATS). The concentrations and elimination rates of several inflammatory
      markers [IL-1beta, IL-2, IL-8, TNFalpha, myeloperoxidase (MPO), elastase] were
      examined. Except for the Sequestra, an important increase in concentration of IL
      1beta (between 30% and 220%) has been observed after processing with each device.
      In contrast, the attenuation rate of IL-6 and TNFalpha (95%) was optimal for all
      investigated blood salvages systems. Regarding IL-8, only the CATS and CS5
      systems were able to attenuate this biological parameter with an excellent
      efficacy. The rate of attenuation in MPO and elastase, as markers of leukocyte
      activation, was higher than 80% for all devices. In conclusion, the different RBC
      washing systems tested in this study resulted in a significant attenuation of the
      inflammatory response. Increased levels of IL-1beta after processing remained,
      however, unclear. According to the type of protocol, based on inlet haematocrit,
      fill and wash speeds, and wash volumes, small variations in reducing the
      inflammatory response have been observed from one device to another.

PMID- 11958303
TI  - An in vitro method for comparing biocompatibility of materials for extracorporeal
      circulation.
AB  - We measured the response of fresh heparinized human blood to recirculation
      through circuits made of LVA (Portex Industries, Hythe, Kent, UK), SRT (Rehau UK,
      Langley, Slough, UK) and Tygon S-65-HL (Norton Performance Plastics, Corby,
      Northants, UK), as control. Circuit construction: 1/2 in. tubing, heat exchanger
      (Dideco D-720P), Stockert roller pump, just underoccluded, Cincinnati Sub Zero
      heater, circuit volume of 500 ml. Flow 3.45 l/min, 37 degrees C. SAMPLES: at 10
      min, 1, 2, 4 and 6 h. n=5 in each group; 2/5 SRT experiments were stopped at 45
      and 60 min due to overpressurization. RESULTS: Baseline activated clotting time
      (ACT) of 300 s, increasing in all groups as fibrinogen fell to zero with SRT and
      LVA. Minimum fibrinogen was 1 g/l for Tygon. Absolute thrombocytopenia occurred
      (SRT and LVA 60 min and Tygon 240 min). International normalized ratio (INR) in
      both the SRT and LVA circuits increased, but mean increase for Tygon (0.56) was
      smaller than the other two materials. Plasma free haemoglobin increased in all
      three materials; the increase was greater in the LVA circuits compared to the
      control. C5b9 levels increased equally in all groups. Lactoferrin levels rose
      equally in all groups to a maximum at 150 min. The neutrophil counts fell,
      mirroring the lactoferrin. The total white cell counts also fell in all groups;
      in the LVA circuits, the fall was significantly lower than in the control. Rapid
      disappearance of platelets and fibrinogen from the blood in the SRT and LVA
      circuits excludes them both from extracorporeal use. Paradoxically, SRT caused
      the least complement activation of the three materials. This method can be used
      to compare biocompatibility.

PMID- 11958304
TI  - The relationship between mixed venous and regional venous oxygen saturation
      during cardiopulmonary bypass.
AB  - The relationship between mixed venous and regional venous saturation during
      cardiopulmonary bypass (CPB), and whether this relationship is influenced by
      temperature, has been incompletely elucidated. Thirty patients undergoing valve
      and/or coronary surgery were included in a prospective, controlled and randomized
      study. The patients were allocated to two groups: a hypothermic group (28 degrees
      C) and a tepid group (34 degrees C). Blood gases were analysed in blood from the
      hepatic vein and the jugular vein and from mixed venous blood collected before
      surgery, during hypothermia, during rewarming, and 30 min after CPB was
      discontinued. Oxygen saturation in the hepatic vein was lower than in the mixed
      venous blood at all times of measurement (-24.0 +/- 3.0% during hypothermia, 
      36.5 +/- 2.9% during rewarming, and -30.5 +/- 3.0% postoperatively, p < 0.001 at
      all time points). In 23% of the measurements, the hepatic saturation was <25% in
      spite of normal (>60%) mixed venous saturation. There was a statistical
      correlation between mixed venous and hepatic vein oxygen saturation (r=0.76, p <
      0.0001). Jugular vein oxygen saturation was lower than mixed venous saturation in
      all three measurements (-21.6 +/- 1.9% during hypothermia, p < 0.001; -16.7 +/-
      1.9% during rewarming, p < 0.001; and -5.6 +/- 2.2% postoperatively, p = 0.037).
      No significant correlation in oxygen saturation could be detected between mixed
      venous and jugular vein blood (r = 0.06, p = 0.65). Systemic temperature did not
      influence the differences in oxygen saturation between mixed venous and regional
      venous blood at any time point. In conclusion, regional deoxygenation occurs
      during CPB, in spite of normal mixed venous saturation. Mixed venous oxygen
      saturation correlates with hepatic, but not with jugular, vein saturation. The
      level of hypothermia does not influence differences in oxygen saturation between
      mixed venous and regional venous blood.

PMID- 11958306
TI  - Should we rely on nasopharyngeal temperature during cardiopulmonary bypass?
AB  - A potential morbidity of incomplete re-warming following hypothermic
      cardiopulmonary bypass (CPB) is cardiac arrest. In contrast, attempts to fully re
      warm the patient can lead to cerebral hyperthermia. Similarly, rigid adherence to
      37.0 degrees C during normothermic CPB may also cause cerebral overheating. The
      literature demonstrates scant information concerning the actual temperatures
      measured, the sites of temperature measurement and the detailed thermal
      strategies employed during CPB. A prospective, randomized, controlled study was
      undertaken to investigate the ability to manage perfusion temperature control in
      a group of hypothermic patients (28 degrees C) and a group of normothermic
      patients (37 degrees C). Eighty patients presenting for first-time, elective
      coronary artery bypass graft surgery (CABG) were randomly allocated to the
      hypothermic and normothermic groups. All surgery was performed by one surgeon and
      the anaesthesia managed by one anaesthetist. Temperature measurements were made
      at the nasopharyngeal (NP) site, as well as in the arterial line of the CPB
      circuit. The hypothermic group had the arterial blood temperature lowered to 25.0
      degrees C to maintain the NP temperature at 28.0-28.5 degrees C. During re
      warming, the arterial blood was raised to 38.0 degrees C. Meanwhile, in the
      normothermic group, the arterial blood temperature was raised to a maximum of
      37.0 degrees C to maintain NP temperature at 36.5-37.0 degrees C. Despite strict
      guidelines, some patients transgressed the temperature control limits. Two
      patients in the hypothermic group failed to reach an NP temperature of 28.5
      degrees C. Twenty-six patients were managed entirely within the control limits.
      During rewarming in both groups, control of both arterial and NP temperature was
      well managed with only 25% patients breaching the respective upper control
      limits. During the re-warming phases of CPB, we were unable to make any
      correlation between NP temperature and arterial blood temperature, using body
      weight or body mass index as predictors. Based on the results obtained, we
      recommend that strict criteria should be implemented for the management of
      temperature during CPB, in conjunction with more emphasis being placed on
      monitoring arterial blood temperature as a marker of potential cerebral
      hyperthermia. We should, therefore, not rely on NP temperature measurement alone
      during CPB.

PMID- 11958305
TI  - Conventional approach to glucose management for diabetic patients undergoing
      coronary artery bypass surgery.
AB  - Continuous insulin infusion was not an effective mode of treatment in maintaining
      safe blood glucose levels (<200 mg/dl) during the intraoperative period of
      diabetic patients requiring open-heart surgery. The two modifications
      investigated to gain better control of the blood glucose were a change in the
      base solution of the cardioplegia and the use of a sliding insulin scale. Fifty
      patients including Type I and Type II diabetics were selected for the purpose of
      this study. The patients were then randomly divided into two groups categorized
      by the type of cardioplegic solution administered and the mode of insulin
      treatment. Group I patients received a dextrose 5%-based cardioplegic solution
      and blood glucose was treated via continuous intravenous insulin infusion. Group
      II patients received normal saline 0.9%-based cardioplegic solution and blood
      glucose was treated via sliding scale. Blood glucose levels were monitored pre-
      and postcardiopulmonary bypass (CPB) and every 30 min while on CPB. Glucose
      values were analyzed by group t test. A p value of <0.05 was considered
      statistically significant. When comparing Group I (mean=258 mg/dl) with Group II
      (mean=158 mg/dl), there was a statistically significant difference between the
      glucose values at each of the time intervals when the glucose values were
      recorded. In conclusion, Group II maintained an acceptable blood glucose level
      (<200 mg/dl) throughout the entire intraoperative period, which suggests that the
      combination of the sliding insulin scale and modification of the base
      cardioplegic solution was an effective mode of treatment.

PMID- 11958307
TI  - In vitro hydrodynamics of the Embol-X cannula.
AB  - BACKGROUND: Prevention of intraoperative plaque dislodgement in patients with
      atherosclerotic ascending aorta by development of innovative aortic cannula
      designs gains growing interest in cardiac surgery. To increase knowledge about
      the hydrodynamics of the innovative Embol-X cannula, which includes an intra
      aortic filter device targeting at atheromatous emboli capture, was the aim of the
      present study. METHODS: Pressure gradients and back pressures of the Embol-X
      cannula were measured at varying flow rates in a mock circulation and compared
      with two commonly used single-stream cannulae. RESULTS: At a flow rate of 5.5
      l/min, pressure gradients across the Argyle and the RMI cannulae were 48% and 62%
      and back pressures 25% and 47% lower than the corresponding values across the
      Embol-X cannula. CONCLUSIONS: The novel concept of integrating a filter device
      may provide clinical advantages concerning neurologic outcome. Further in vivo
      studies seem to be desirable to obtain more information concerning the clinical
      effects of the Embol-X cannula hydrodynamics.

PMID- 11958308
TI  - A 10-year review of pediatric perfusion practice in North America.
AB  - In December 1999, 145 North American pediatric open-heart institutions were
      mailed an updated survey as a follow-up of two earlier surveys, 1989 and 1994.
      The survey consisted of 81 questions pertaining to demographics, equipment,
      techniques and patient monitoring. This survey, following a similar format of the
      two earlier surveys, provides a 10-year review encompassing both new and founded
      practices performed during the conduct of pediatric cardiopulmonary bypass.
      Responses were received from 83 hospitals, for a 57% response rate. Of the
      respondents, 72 were active pediatric open-heart centers, 67% performing both
      adult and pediatric cardiac surgery and 33% performing pediatric surgery
      exclusively. The mean number of pediatric cases performed in 1999 was 169,
      compared to 101 cases in 1989 and 145 cases in 1993. Of the 72 respondents, 51%
      were performing greater than 100 cases/year, whereas 3% of centers were
      performing under 25 cases/year. As the decade progressed, bubble oxygenators were
      completely replaced by their membrane counterpart. The use of ultrafiltration,
      reported first in the 1989 survey, has risen by over 30%. The use of colloids in
      the prime, specifically 25% albumin, has increased in use from 34% in 1989 to 85%
      in 1999. Rewarming gradients are used by 100% of respondents with a mean gradient
      of 9.4 degrees C between the patient and water bath. Myocardial protection has
      seen an increase of close to 20% in the use of blood cardioplegia. The use of
      safety devices is also on the rise with more centers using level detectors (79%),
      bubble detectors (88%) and arterial line filters (96%). Centers relying on the
      use of cardiac assist devices have increased by 25% since 1989. Results of this
      survey suggest a movement toward a higher volume of cases being performed at
      fewer centers. While some diversity is seen, movement toward greater homogeneity,
      first noted in the 1994 survey, continues in 1999.

PMID- 11958309
TI  - Clinical outcomes of on-pump coronary bypass using heparin-bonded circuits and
      reduced anti-coagulation compare favorably with off-pump approach.
AB  - Coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB), or
      off pump, has gained popularity by avoiding the postoperative morbidity related
      to the use of CPB. Previously, we have demonstrated that CABG done on pump using
      heparin-bonded cardiopulmonary bypass circuits (HBC) with a lower anti
      coagulation protocol (LAP) attenuates these effects, reduces homologous blood
      product requirement, and improves clinical outcome when compared with
      conventional CPB circuits. Our purpose in this study was to compare off-pump CABG
      clinical outcomes to on-pump CABG using HBC with LAP. We retrospectively analysed
      preoperative and postoperative variables of all primary CABG (n=1214) performed
      at this institution from 1 January 1997 to 28 July 2000. These patients were
      divided into the on-pump (n=1152) and off-pump groups (n=62). HBC with LAP were
      used in all on-pump CABG cases. There was no statistical difference in
      preoperative comorbid risk factors except percentage of females (on pump, 30% vs.
      off pump, 44%; p=0.02) and body surface area (on pump, 1.94 +/- 0.25 ml vs. off
      pump, 1.85 +/- 0.22 ml; p=0.02). There was no difference in intraoperative and
      postoperative complications, risk-adjusted mortality, total blood product usage,
      or length of stay. The mean number of distal anastomoses performed was
      significantly different (on pump, 3.5 +/- 0.82 vs. off pump 1.8 +/- 0.82; p <
      0.001). Despite similar preoperative risk factors, clinical outcomes and
      homologous blood requirements were not statistically different between the off
      pump and on-pump groups. These endpoints should not be the only criteria to
      justify performing off-pump CABG.

PMID- 11958310
TI  - Heparin-bonded circuits without a cardiotomy: a description of a minimally
      invasive technique of cardiopulmonary bypass.
AB  - The deleterious effects of cardiotomy suction have been well recognized and well
      documented for some time. The use of cardiotomy suction results in the exposure
      of blood to the defoaming sock, aspiration of stagnant pericardial blood into the
      systemic circulation, and the entrainment of both fatty and gaseous microemboli.
      The purpose of this paper is to describe a technique using heparin-bonded
      cardiopulmonary circuits (HBCs) without the use of a cardiotomy reservoir or
      cardiotomy suction. Our group has previously demonstrated improved clinical
      outcomes using HBCs and a low-dose anti-coagulation protocol. It is our goal to
      further improve clinical outcomes and further attenuate the deleterious effects
      of cardiopulmonary bypass by eliminating the potential complications attributed
      to the use of cardiotomy suction.

PMID- 11958311
TI  - High or low hematocrits during cardiopulmonary bypass for patients undergoing
      coronary artery bypass graft surgery? An evidence-based approach to the question.
AB  - We have observed an inverse relationship between a CPB Hct <20% and the need for
      cardiac support and hospital mortality. These data call for an aggressive and
      concerted effort to avoid a CPB Hct of <20%. The focus should be directed at
      women and small men since this subset of patients are most likely to experience
      low CPB Hct. A comprehensive, multimodality blood-conservation plan that involves
      the use of erythropoietin, aprotinin, preoperative autologous donation, shed
      blood reinfusion, and minimal phlebotomy for blood testing was proposed by
      Rosengart and colleagues based on their experience in caring for 50 Jehovah's
      Witness patients. Efforts to conserve blood and ensure hemostasis should cover
      the entire spectrum of care, including preoperative phlebotomy (for blood tests),
      diagnostic and interventional procedures, and intraoperative and postoperative
      care. Further work is needed to understand the mechanism for the relationship
      between low Hct and adverse outcomes. Each open-heart center should consider the
      Hct question carefully, examining both the published literature and their own
      results related to CPB Hct and patient outcomes.

PMID- 11958312
TI  - Benefits of cerebral protection during carotid stenting with the PercuSurge
      GuardWire system: midterm results.
AB  - PURPOSE: To examine the possible beneficial effect of a new cerebral protection
      device based on balloon occlusion of the distal internal carotid artery (ICA) and
      debris aspiration for patients undergoing carotid artery stenting (CAS). METHODS:
      One hundred and eighty-four CAS procedures were attempted under cerebral
      protection using the PercuSurge GuardWire system in 167 patients (129 men; mean
      age 70.5 +/- 9.2 years, range 40-91)). The lesions were mainly atherosclerotic,
      and half (n = 93) were asymptomatic. Eighteen restenotic and 7 post-radiation
      stenoses were also treated. RESULTS: Technical success was 99.5%. All lesions
      were stented except 3 postangioplasty restenoses. Prophylactic occlusion during
      balloon dilation and stenting was well tolerated in 176 (95.7%) patients.
      Microscopic analysis of the aspirated blood showed different types of particles
      numbering between 7 and 145 per procedure with a mean diameter of 250 microm (56
      2652 microm). The 30-day stroke and death rate was 2.7%: 3 periprocedural
      complications at <48 hours (1 major stroke and 2 transient ischemic attacks), 1
      intracerebral hemorrhage at 3 days, and 1 death of cardiac failure at 3 weeks.
      CONCLUSIONS: This study yielded a favorably low rate of periprocedural embolic
      events comparable with standard CAS series. Protection devices may play an
      important role in future carotid interventions and expand the applicability of
      the procedure. Randomized studies (surgery versus CAS with and without cerebral
      protection) are awaited.

PMID- 11958313
TI  - CT artifacts of the proximal aortic neck: an important problem in endograft
      planning.
AB  - PURPOSE: To describe the imaging error introduced by noncircular abdominal aortic
      aneurysm (AAA) necks in axial and reformatted computed tomographic (CT) images
      and discuss the potential implications for aortic endografting. METHODS: The
      records of 120 endograft patients with preoperative CT axial scans and subsequent
      3-dimensional (3D) computerized reconstructions were reviewed. Maximum and
      minimum infrarenal aortic neck diameters were measured from axial CT scans and 3D
      reformatted slices at the same point on the vessel. Diameter measurements were
      made at the largest point within the 10-mm segment of vessel below the lowest
      renal artery. Excluded were aneurysms with proximal neck minimum diameters >30
      mm, neck lengths < 15 mm, or angulation > 75 degrees measured on the axial CT
      slice. RESULTS: Measuring from reformatted CT slices, 86 (71.6%) cases had < or =
      2-mm differences between maximal and minimal neck diameters, comprising the
      "round neck" group A. In 34 (28.4%) cases, the neck was not round: 26 (21.7%) had
      diameter differences between 2 and 4 mm (group B) and 8 (6.7%) had a > 4-mm
      difference (group C; range 4.1-8.1 mm). Although AAA diameter, neck length, and
      neck angle progressively increased as the difference between neck maximum and
      minimum diameters grew, i.e., greater eccentricity, these trends did not reach
      statistical significance. Mean infrarenal neck maximum diameter was significantly
      larger in group C (30.2 +/- 3.4 mm) compared to groups A (23.0 +/- 2.9 mm, p =
      0.0002) and B (23.8 +/- 3.6 mm, p = 0.0003). Hence, 28.4% of AAAs had a
      noncircular aortic neck of varying degree, and 6.7% had an eccentricity factor
      that may have clinical significance. CONCLUSIONS: This study confirms the
      importance of selecting an endoprosthesis sized 15% to 20% larger than the
      infrarenal aortic neck diameter. Three-dimensional reconstruction using
      reformatted CT slices perpendicular to the flow lumen is an important tool that
      offers enhanced accuracy of infrarenal aortic neck evaluation.

PMID- 11958314
TI  - Surgical conversion after endovascular grafting for abdominal aortic aneurysms.
AB  - PURPOSE: To analyze the indications, results, and technical problems associated
      with conversion after endoluminal repair of abdominal aortic aneurysms (AAA)
      based on a 6-year experience in endovascular grafting. METHODS: From August 1994
      to May 2000, 520 patients with AAA were deemed candidates for endovascular
      therapy based on data from contrast-enhanced computed tomography and aortography.
      Any conversions were performed using an open operation modified according to the
      indication for conversion, elapsed time from the endoluminal repair, and type of
      endograft (tube, bifurcated, infra-/suprarenal fixation). RESULTS: Conversion to
      open repair was required in 37 (7.1%) cases: 23 tube grafts and 14 bifurcated
      devices. Seventeen (3.2%) conversions occurred at the original operation and 20
      (3.8%) were performed secondarily. Indications for primary conversion were mainly
      device defects (n = 5) or access problems (n = 5), while secondary conversion was
      primarily owing to type I endoleak (n = 16). The conversion rate was
      significantly higher in modular devices (5.9%) than unibody designs (1.4%) (p =
      0.003). The rate of primary conversions diminished from 10.9% in 1994-1995 to
      2.4% between 1996 and 2000, as did the overall mortality rate, from 8.3% in the
      first time period to 0% in the second for elective conversions, but emergency
      operations had 40% mortality. CONCLUSIONS: Most AAAs require bifurcated devices
      for complete exclusion, and older model modular grafts have higher conversion
      rates. Primary conversion decreases as more experience in endoluminal grafting is
      acquired. Emergency open repair results in a high mortality rate.

PMID- 11958316
TI  - A useful endovascular technique for treating modular limb disconnection in a
      bifurcated stent-graft.
AB  - PURPOSE: To report a technique for treating a type III endoleak owing to
      disconnection of an iliac graft limb from a modular aortic stent-graft.
      TECHNIQUE: A hydrophilic guidewire is introduced via a homolateral femoral access
      and passed through the thrombosed iliac extension. Once the errant graft limb is
      recanalized, wire exchange for an extra stiff guidewire facilitates passage of an
      angioplasty balloon into the stent. Inflated under low pressure, the balloon is
      used to push the thrombosed limb retrograde into the aneurysm sac. With the
      aortoiliac axis restored, a new covered stent can be deployed. CONCLUSIONS: This
      approach is one of several that may be used to treat a type III endoleak arising
      from a disconnected and occluded stent-graft limb. It avoids the bleeding
      complications of thrombolysis and restores the aortoiliac axis so that another
      stent-graft may be implanted to re-exclude the aneurysm.

PMID- 11958315
TI  - "Pseudoendoleak"--residual intrasaccular contrast after endovascular stent-graft
      repair.
AB  - PURPOSE: To present a unique demonstration of postoperative perigraft contrast
      masquerading as an endoleak following endovascular abdominal aortic aneurysm
      (AAA) repair. CASE REPORT: A 66-year-old man underwent endovascular stent-graft
      repair of a 4.6-cm infrarenal AAA. The procedure was uncomplicated, and
      intraoperative completion angiography demonstrated good proximal and distal
      fixation of the stent-graft without an endoleak. A spiral computed tomographic
      (CT) angiogram obtained on postoperative day 2 revealed a large amount of
      extrastent contrast along the posterior aspect of the aneurysm sac. This defect
      had the appearance of an endoleak, but it was also present on the non-contrast
      images. A color-flow duplex examination performed on the same day showed a widely
      patent stent-graft with no evidence of extrastent flow. CONCLUSIONS: Contrast
      trapped in the aneurysm sac during endovascular aneurysm repair may be
      misinterpreted as an endoleak on postprocedural CT scans. "Pseudoendoleaks" can
      be distinguished from true endoleaks by examination of prebolus, noncontrast CT
      images, as well as by duplex ultrasound scanning.

PMID- 11958317
TI  - Emergent axillary artery stent-graft placement for massive hemorrhage from an
      avulsed subscapular artery.
AB  - PURPOSE: To report the successful endovascular repair of an acute axillary artery
      hemorrhage. CASE REPORT: An 87-year-old woman with Charcot-Marie-Tooth ataxia
      presented with an enormous shoulder hematoma and clinical signs of exsanguination
      after a fall. Angiography demonstrated complete avulsion of the right subscapular
      artery from the axillary artery, and active bleeding into a hematoma of at least
      1500 mL. Endovascular repair with a balloon-mounted covered stent-graft was
      performed percutaneously, which controlled the bleeding and averted surgery. The
      patient recovered uneventfully and was without signs of recurrent bleeding or
      ischemia on the 6-month ultrasound examination; she reports no symptoms referable
      to her upper extremity after 14 months. CONCLUSIONS: Endovascular repair with
      stent-grafts is effective in controlling arterial bleeding from supra-aortic
      vessels even under emergency conditions.

PMID- 11958319
TI  - Carotid artery stenting for stenosis following revascularization or cervical
      irradiation.
AB  - PURPOSE: To assess the safety and efficacy of carotid artery stenting (CAS) for
      stenosis following revascularization or cervical irradiation. METHODS: Twenty-two
      CAS procedures performed on 21 patients (20 men; mean age 69.3 years, range 58
      87) from June 1997 to June 2000 were retrospectively reviewed. There were 5
      radiation-induced carotid stenoses in 4 patients and 17 postsurgical restenoses.
      The mean interval between carotid revascularization and CAS was 48.1 months
      (range 6-264), while the elapsed time from irradiation to CAS was always >8 years
      (range 8-28). Seven patients screened during this period were excluded from CAS
      because of a duplex-defined >50% hypoechoic lesion and/or angiographic
      documentation of an irregular ulcerated stenosis. RESULTS: Four Palmaz and 16
      Wallstents were successfully deployed in 20 arteries; 1 access failure prompted
      conversion to surgery and a stent delivery failure resulted in 1 patient
      receiving balloon dilation only (technical success 91%). No complications were
      encountered in the periprocedural period, and no neurological events were
      observed during a mean follow-up of 16.6 months (range 3-36). One patient died at
      20 months from an unrelated cause. One (4.8%) restenosis was detected after 1
      year in the patient who did not receive a stent. CONCLUSIONS: CAS is a safe
      alternative to conventional surgery in patients with carotid artery stenosis
      following surgical revascularization or cervical irradiation provided
      preoperative testing excludes stenoses at risk for embolism.

PMID- 11958318
TI  - Fenestrated stent-graft for traumatic juxtahepatic inferior vena cava injury.
AB  - PURPOSE: To report the use of a fenestrated stent-graft to manage a traumatic
      rupture of the juxtahepatic inferior vena cava (IVC). CASE REPORT: A 62-year-old
      man was involved in a traffic accident and hospitalized for severe right leg
      fractures. Computed tomography also uncovered liver contusion and retroperitoneal
      hematoma. The next day, he became hemodynamically unstable; a huge
      retroperitoneal hematoma had developed from a rupture of the juxtahepatic IVC. An
      emergent procedure to implant a self-expanding fenestrated stent-graft was
      successful in repairing the IVC injury and maintaining hepatic venous return. The
      patient recovered and continues in good health with a patent endograft 16 months
      after treatment. CONCLUSIONS: This experience supports the efficacy of
      fenestrated endograft implantation for emergent repair of IVC injuries, although
      proper facilities, an experienced interventional team, and an assortment of
      devices must be available.

PMID- 11958320
TI  - "Seat belt and air bag" technique for cerebral protection during carotid
      stenting.
AB  - PURPOSE: To present a 2-device technique for cerebral protection during carotid
      stenting of the internal carotid artery (ICA) in patients with high-grade
      lesions, contralateral occlusion, and/or an aberrant or nonfunctioning circle of
      Willis. TECHNIQUE: A reverse flow system (Parodi Anti-Embolism System [PAES]) is
      first placed with a 260-cm exchange wire in the common carotid artery 3 cm below
      the carotid bifurcation. Flow reversal is obtained by inflating the balloons in
      the external and common carotid arteries. Via an external connector, a guidewire
      and E-Trap filter are delivered to the distal ICA with active suction from a
      syringe on the PAES catheter. Once the filter is above the stenosis, the reversed
      flow is discontinued, and the procedure proceeds under cerebral protection with
      the filter. CONCLUSIONS: The combination of 2 existing cerebral protection
      devices could, at least in theory, achieve what neither of them could
      independently. The "seat belt and air bag" approach may represent the ideal means
      of treating ICA stenoses in patients with a non-functioning circle of Willis.

PMID- 11958321
TI  - Percutaneous thrombin injection of carotid artery pseudoaneurysm.
AB  - PURPOSE: To report the successful treatment of a carotid artery pseudoaneurysm by
      percutaneous thrombin injection. CASE REPORT: A 71-year-old man with end-stage
      renal failure presented with acute left ventricular failure. The right common
      carotid artery (CCA) was punctured during attempted jugular line insertion, and
      he developed a large pseudoaneurysm connected to the CCA by a long, narrow neck.
      Ultrasound-guided compression was unsuccessful, so another technique was
      attempted. An occlusion balloon was inflated in the CCA at the neck of the
      aneurysm to avoid distal embolization, and 250 units of human thrombin were
      injected into the sac percutaneously; thrombosis was instantaneous. There were no
      procedural complications, and repeat ultrasound at 3 months showed resolution of
      the hematoma and no residual pseudoaneurysm. There were no neurological
      complications. CONCLUSIONS: Percutaneous thrombin injection may be a new and
      successful method of treating carotid artery pseudoaneurysms.

PMID- 11958322
TI  - Autologous thrombin: a new embolization treatment for traumatic intrasplenic
      pseudoaneurysm.
AB  - PURPOSE: To report the use of autologous thrombin for transcatheter embolization
      of a traumatic parenchymal splenic pseudoaneurysm. CASE REPORT: A 15-year-old boy
      presented with a splenic parenchymal laceration after blunt abdominal trauma. The
      patient was managed conservatively but developed an intrasplenic pseudoaneurysm
      (grade III AAST scale) with subcapsular contrast extravasation after 3 weeks.
      Autologous thrombin was isolated from the patient's blood and subsequently
      delivered to the lesion by transcatheter superselective injection into the
      aneurysm neck. The patient was asymptomatic after the procedure. Nine months'
      follow-up demonstrated a normal spleen with completely homogenous parenchyma.
      CONCLUSIONS: Autologous thrombin injection to induce thrombosis of intrasplenic
      pseudoaneurysm represents a new treatment option for traumatic abdominal organ
      injuries. Intrasac thrombosis can be safely induced to successfully restore the
      splenic parenchymal integrity without introduction of foreign material and
      associated risks of adverse reactions or infection that might accompany the use
      of commercial thrombin preparations.

PMID- 11958323
TI  - Thrombin injection for pseudoaneurysm occlusion: technical considerations.

PMID- 11958325
TI  - Delayed pseudoaneurysm after renal artery angioplasty.
AB  - PURPOSE: To report delayed pseudoaneurysm formation after percutaneous renal
      artery angioplasty. CASE REPORTS: A 56-year-old woman succumbed to complications
      of a ruptured right juxtarenal aortic pseudoaneurysm 2 years after right renal
      artery stenting for renal impairment. The juxtarenal aorta had been normal on
      aortography at the time of angioplasty. She gave a history of right-sided back
      pain that started within 8 months of the angioplasty. A 21-year-old woman with
      left renal artery stenosis due to fibromuscular dysplasia was treated with
      balloon angioplasty, after which there was evidence of active extravasation. The
      completion angiogram, after a period of observation, documented cessation of the
      leak. Follow-up angiography because of persisting hypertension disclosed a large,
      asymptomatic, intrarenal pseudoaneurysm that was repaired with bench surgery and
      autotransplantation. CONCLUSIONS: We advise that patients with symptoms referable
      to the site of renal artery intervention and those who have had complicated
      interventions should have follow-up imaging to exclude pseudoaneurysm formation.

PMID- 11958324
TI  - Endovascular treatment of visceral artery aneurysms.
AB  - PURPOSE: To review a 10-year experience with endovascular embolization of
      visceral artery aneurysms. METHODS: Twenty-five patients (13 men; mean age 52.1
      years, range 31-80) presented with VAAs of varying locations and etiologies: 10
      splenic, 3 gastroduodenal, 2 pancreaticoduodenal, 3 hepatic, 3 superior
      mesenteric, 2 celiac, 1 left gastric, and 1 jejunoileal. Ten patients were
      asymptomatic; 7 aneurysms were ruptured. Transcatheter coil embolization was the
      treatment of choice in all patients. RESULTS: Coil placement was initially (<7
      days) successful in 23 (92%) patients. One superior mesenteric artery aneurysm
      remained perfused, and recurrent bleeding occurred 2 days after intervention in 1
      case, but repeated embolization excluded the aneurysm. One patient with
      necrotizing pancreatitis died from sepsis 10 days after endovascular treatment
      and surgery (4% 30-day mortality). Long-term follow-up revealed excellent results
      after an average 48.7 months (range 14-75) with only 1 recurrence after 12
      months. CONCLUSIONS: Embolotherapy is the treatment of choice in visceral artery
      aneurysms, regardless of etiology, location, or clinical presentation.

PMID- 11958326
TI  - Renal artery aneurysm: improved renal function after coil embolization.
AB  - PURPOSE: To describe a case of improved renal function and renovascular
      hypertension after percutaneous treatment of a renal artery aneurysm. CASE
      REPORT: A 72-year-old hypertensive woman with a hilar saccular aneurysm of the
      right renal artery underwent percutaneous coil embolization under local
      anesthesia. Four individual, soft, detachable platinum embolization coils were
      successfully inserted in the aneurysm with incomplete aneurysm exclusion.
      Nonetheless, the patient's blood pressure and renal function returned to normal.
      The arteriogram at 3 months demonstrated complete exclusion of the lesion and
      good renal perfusion. The patient remains normotensive with documented improved
      renal function at 18 months after treatment. CONCLUSIONS: Superselective coil
      embolization is an effective treatment for renal artery aneurysms that display
      proper morphological features. The long-term outcome of this less invasive
      therapy still must be assessed, but it appears plausible that embolotherapy of
      renal artery aneurysms can correct secondary hypertension and deteriorating renal
      function.

PMID- 11958327
TI  - Balloon angioplasty and stent implantation induce a vascular inflammatory
      reaction.
AB  - PURPOSE: To investigate whether peripheral balloon angioplasty with and without
      stent implantation independently causes an inflammatory vascular response
      measured by serum acute-phase reactants. METHODS: This was a prospective cohort
      study enrolled 388 consecutive patients (218 men; median age 70 years,
      interquartile range 59-76) with peripheral artery disease undergoing balloon
      angioplasty (n = 187), stent implantation (n = 140), and diagnostic angiography
      (control group, n = 61). C-reactive protein (CRP) measured by standard and high
      sensitivity assays, serum amyloid A (SAA), fibrinogen, and white blood cell (WBC)
      count were obtained at baseline and at 8, 24, and 48 hours postintervention.
      Polynomial logistic regression analysis was used to assess the independent
      association of acute-phase reactants and the interventional group. RESULTS: CRP
      levels measured by both standard and the high-sensitivity assays significantly
      increased after balloon angioplasty (standard CRP, p = 0.02; high-sensitivity
      CRP, p = 0.02) and stent implantation (standard CRP, p = 0.004; high-sensitivity
      CRP, p = 0.008) compared to the control group adjusting for age, sex, duration of
      fluoroscopy, volume of contrast, and periprocedural complications. SAA values
      differed only between the stent group and controls (p = 0.05). Fibrinogen and
      WBCs were not different among the 3 interventional groups. CONCLUSIONS: Balloon
      injury and stent implantation induce a vascular inflammatory response at the
      dilated vessel segment measurable by serum acute-phase parameters. The standard
      CRP assay is adequate to quantify acute-phase response in these patients.

PMID- 11958328
TI  - Long-term results of stenting for chronic iliac artery occlusion.
AB  - PURPOSE: To evaluate the long-term results of stent placement for chronic
      occlusions of the iliac arteries. METHODS: Between October 1992 and December
      1997, 73 patients (40 men; median age 64 years, range 42-89) with 76 occluded
      iliac arteries (33 common, 34 external, and 9 both vessels) were treated with
      percutaneous recanalization and stenting using a variety of self-expanding and
      balloon-expandable devices. Median occlusion length was 7 cm (range 1-14). Follow
      up consisted of clinical assessment, ankle-brachial index measurement, and
      arteriography or duplex ultrasound when indicated. RESULTS: Anatomical success
      was achieved in 74 (97%) limbs. Seven (10%) patients experienced major
      complications: 2 distal embolizations, 2 arterial ruptures, 1 myocardial
      infarction, 1 groin hematoma requiring surgery, and 1 contrast-induced
      nephropathy. There was no 30-day mortality. Over a median follow-up of 27 months
      (range 1-75), there was 1 early occlusion (< or = 30 days) and 16 late recurrent
      lesions (11 occlusions and 5 stenoses) at a median 6.2 months (range 1.4-30). The
      recurrent lesions were treated with endovascular techniques in 8 limbs and
      surgery in 7 limbs (5 after failed endovascular procedures); 1 patient died
      before retreatment, and 1 patient refrained from further intervention. Primary
      and secondary patencies were 79% and 87% at 1 year and 69% and 81% at 3 years,
      respectively. CONCLUSIONS: Stenting of chronic iliac occlusions is a safe and
      durable alternative to surgical treatment.

PMID- 11958329
TI  - Waligraft endoprosthesis for the percutaneous treatment of femoral and popliteal
      artery aneurysms.
AB  - PURPOSE: To evaluate the safety and efficacy of the Wallgraft Endoprosthesis for
      the treatment of femoropopliteal artery aneurysms. METHODS: From October 1997 to
      April 2000, 17 patients (13 men; mean age 73.5 +/- 7.1 years) with 7 femoral and
      13 popliteal artery aneurysms underwent percutaneous aneurysm exclusion using the
      Wallgraft Endoprosthesis as part of a larger clinical trial. The mean aneurysm
      diameters were 37.6 +/- 12.9 mm and 22.3 +/- 8.7 mm, respectively. RESULTS: Acute
      procedural success was 100% for femoral aneurysms and 92.3% (12/13) in the
      popliteal artery owing to one endoleak that resolved after 1 month. There were no
      complications, and the mean length of stay was 2.2 +/- 3.8 days. Six-month and 1
      year aneurysm exclusion rates were 100% for both locations, but 4 (31%) popliteal
      stent-grafts thrombosed in follow-up. Three were recanalized, but the fourth
      underwent bypass grafting after 3 thrombotic episodes. The 1-year primary and
      secondary patency rates were both 100% for the femoral aneurysms and 69% and 92%,
      respectively, for popliteal repairs. No procedure or device-related deaths
      occurred. CONCLUSIONS: Treatment of aneurysms in the femoropopliteal segment
      appears to be safe and effective with the Wallgraft Endoprosthesis, although
      longer follow-up in a larger patient group will be needed to determine this
      technique's potential versus surgical repair.

PMID- 11958330
TI  - Outcome after endovascular abdominal aortic aneurysm repair: a meta-analysis.
AB  - PURPOSE: To determine the frequencies of complications and risk factors for
      complications following endovascular abdominal aortic aneurysm (AAA) repair
      (EVAR). METHODS: Thirty-nine articles published between October 1995 and October
      1999 in English, German, French, or Dutch were identified in electronic
      databases. All articles reported perioperative (30-day) complications on 2387
      patients, while postoperative complications (>30 days) were reported on 1645
      patients in 30 of 39 studies. Data were pooled and subjected to multivariable
      logistic regression analysis to identify risk factors for death, endoleak,
      rupture, conversion, and local and systemic complications. Effects of risk
      factors were expressed as odds ratios (OR) with 95% confidence interval (CI).
      RESULTS: Mean follow-up was 13.9 months (range 4-29). The perioperative death
      rate (3.7%) was lower than postoperative mortality (5.0% per annum). The risks
      for both endoleak (13.1%) and conversion (5.0%) were higher in the perioperative
      period than postoperatively (5.4% and 1.4% per annum, respectively). Independent
      risk factors for perioperative complications were: general anesthesia (death: OR
      = 5.1, 95% CI 1.9-13.3); EVT graft (endoleak: OR = 3.0, 95% CI 1.3-7.0); female
      sex (rupture: OR = 2.8, 95% CI 1.4-5.8); hypertension (conversion: OR = 0.03, 95%
      CI 0.0-0.3); age >70 years (conversion: OR = 3.5, 95% CI 1.3-9.2); and team
      experience >30 patients (conversion: OR = 3.0, 95% CI 1.2-1.6). Independent risk
      factors for postoperative complications were: predischarge examination (death: OR
      = 0.2, 95% CI 0.0-0.7); follow-up 30 days after operation (death: OR = 0.3, 95%
      CI 0.1-1.0); and female sex (rupture: OR = 1.4, 95% CI 0.5-4.4; conversion: OR
      6.8, 95% CI 2.0-23.4; and systemic complications: OR = 2.9, 95% CI 1.1-7.5).
      CONCLUSIONS: The risk of complications after EVAR is high, supporting the
      cautious use of EVAR. Both patient characteristics and procedural variables were
      independent risk factors for complications. To avoid the limitations of this
      study, the results of randomized clinical trials must determine if EVAR offers a
      safe and durable alternative to open AAA repair.

PMID- 11958331
TI  - Noninvasive diagnosis of incomplete endovascular aneurysm repair: D-dimer assay
      to detect type I endoleaks and nonshrinking aneurysms.
AB  - PURPOSE: To test the hypothesis that D-dimer (D-D), a cross-linked fibrin
      degradation product of an ongoing thrombotic event, could be a marker for
      incomplete aneurysm exclusion after endovascular abdominal aortic aneurysm (AAA)
      repair. METHODS: In a multicenter study, 83 venous blood samples were collected
      from 74 AAA endograft patients and controls. Twenty subjects who were >6 months
      postimplantation and had evidence of an endoleak and/or an unmodified or
      increasing AAA sac diameter formed the test group. Controls were 10 nondiseased
      subjects >65 years old, 18 AAA surgical candidates, and 26 postoperative
      endograft patients with no endoleak and a shrinking aneurysm. Blood samples were
      analyzed for D-D through a latex turbidimetric immunoassay. The endograft
      patients were stratified into 5 clinical groups for analysis: no endoleak and
      decreasing sac diameter, no endoleak and increasing/unchanged sac diameter, type
      II endoleak and decreasing sac diameter, type II endoleak and
      increasing/unchanged sac diameter, and type I endoleak. RESULTS: Individual D-D
      values were highly variable, but differences among clinical groups were
      statistically significant (p < 0.0001). D-D values did not vary significantly
      between patients with stable, untreated AAAs and age-matched controls (238 +/-
      180 ng/mL versus 421 +/- 400 ng/mL, p > 0.05). Median D-D values increased at 4
      days postoperatively (963 ng/mL versus 382 ng/mL, p > 0.05) and did not vary
      thereafter if there was no endoleak and the aneurysm sac decreased. D-D mean
      values were higher in patients with type I endoleak (1931 +/- 924 ng/mL, p <
      0.005) and those with unchanged/increasing sac diameters (1272 +/- 728 ng/mL)
      than in cases with decreasing diameters (median 638 +/- 238 ng/mL) despite the
      presence of endoleak (p < 0.0005). CONCLUSIONS: Elevated D-D may prove to be a
      useful marker for fixation problems after endovascular AAA repair and may help
      rule out type I endoleak, thus excluding patients from unnecessary invasive
      tests.

PMID- 11958333
TI  - The autolysis of industrial filamentous fungi.
AB  - Fungal autolysis is the natural process of self-digestion of aged hyphal
      cultures, occurring as a result of hydrolase activity, causing vacuolation and
      disruption of organelle and cell wall structure. Previously, authors have
      considered individual aspects of fungal lysis, in terms of either an enzyme, a
      process or an organism. This review considers both the physiology and morphology
      of fungal autolysis, with an emphasis on correlations between enzymological
      profiles and the morphological changes occurring during culture degeneration. The
      involvement of the main groups of autolytic hydrolases is examined (i.e.,
      proteases, glucanases, and chitinases), in addition to the effects of autolysis
      on the morphology and products of industrial bioprocesses. We call for a
      concerted approach to the study of autolysis, as this will be fundamental for
      research to progress in this field. Increased understanding will allow for
      greater control of the prevention, or induction of fungal autolysis. Such
      advances will be applicable in the development of antifungal medicines and enable
      increased productivity and yields in industrial bioprocesses. Using paradigms in
      existing model systems, including mammalian cell death and aging in yeast, areas
      for future study are suggested in order to advance the study of fungal cell
      death.

PMID- 11958332
TI  - Renal infarction following endovascular aortic aneurysm repair: incidence and
      clinical consequences.
AB  - PURPOSE: To investigate the incidence of renal infarction following endovascular
      abdominal aortic aneurysm (AAA) repair, with particular emphasis on a comparison
      of suprarenal versus infrarenal endograft placement. METHODS: Ninety-nine
      patients (92 men; average age 68 years) who had undergone endovascular AAA repair
      between July 1995 and July 1999 and who had at least 12 months' follow-up were
      studied with spiral computed tomographic scans to identify suprarenal endograft
      deployment and renal infarction. RESULTS: Among the 193 renal arteries available
      for study, partial or complete transrenal endograft placement was found in 69
      (36%). Sixteen (8.3%) renal infarctions were identified by the postoperative
      imaging studies. Perfusion of these kidneys was supplied by 6 (8.7%) of the 69
      overstented renal arteries and 7 (5.6%) of the 124 uncovered arteries (p > 0.05).
      In the 3 other cases, intentional accessory renal artery occlusion by the stent
      graft fabric led to frank segmental renal infarctions, which were visualized as
      territorial-perfusion defects affecting up to 27% of the renal volume. In the
      other 13 infarcted kidneys, the punctate deficits involved <10% of the
      parenchymal volume. Renal retention values were unaffected in 15 (94%) of 16
      patients. CONCLUSIONS: Documented renal infarctions following endovascular aortic
      stent-graft placement are not common and do not appear to be associated with
      suprarenal endograft fixation.

PMID- 11958334
TI  - Immunosensors for pesticide analysis: antibody production and sensor development.
AB  - Immunosensors, a type of affinity biosensor, are based on the binding
      interactions between an immobilized biomolecule (antibody/antigen) on the
      electronic transducer surface with the analyte of interest (antigen/antibody),
      resulting in a detectable signal. The sensor system takes advantage of the high
      selectivity provided by the molecular recognition characteristic of an antibody,
      which binds reversibly with a specific antigen. This review article presents the
      current status of immunosensors, highlighting their potential benefits and
      limitations for pesticide analysis. The basic criteria for generating specific
      antibodies against low-molecular-mass pesticides, which are usually
      nonimmunogenic in nature, are briefly discussed. The article also describes the
      fundamentals of important transducer technologies and their use in immunosensor
      development.

PMID- 11958336
TI  - Food-derived carbohydrates--structural complexity and functional diversity.
AB  - Carbohydrates are biomolecules abundantly available in nature. They are found in
      bewildering types ranging from simple sugars through oligo- and polysaccharides
      to glycoconjugates and saccharide complexes, each exhibiting characteristic bio
      physiological and/or nutritional functions both in in vivo and in vitro systems.
      For example, their presence or inclusion in food dictates the texture (body) and
      gives desirable customer appeal (satisfaction), or their inclusion in the diet
      offers beneficial effects of great therapeutic value. Thus, carbohydrates are
      integrally involved in a multitude of biological functions such as regulation of
      the immune system, cellular signaling (communication), cell malignancy,
      antiinfection responses, host-pathogen interactions, etc. If starch is considered
      the major energy storage carbohydrate, the gums/mucilages and other non-starch
      carbohydrates are of structural significance. The most investigated properties of
      starch are its gelatinization and melting behavior, especially during food
      processing. This has led to the development of the food polymer science approach,
      which has enabled a new interpretive and experimental frame work for the study of
      the plasticizing influence of simple molecules such as water, sugars, etc. on
      food systems that are kinetically constrained. Starch, although considered fully
      digestible, has been challenged, and starch is found to be partly indigestible in
      the GI tract of humans. This fraction of starch-resisting digestion in vivo is
      known as resistant starch (RS). The latter, due to its excellent fermentative
      capacity in the gut, especially yielding butyric acid is considered a new tool
      for the creation of fiber-rich foods, which are of nutraceutical importance. By a
      careful control of the processing conditions the content of RS, a man-made fiber,
      can be increased to as high as 30%. Arabinoxylans are the major endospermic cell
      wall polysaccharides of cereals. In wheat they are found complexed with ferulic
      acid esters, which after oxidative coupling in vivo mediated by H2O2 and
      peroxidases or even by photochemical means give cross linked diferuloyl
      derivatives. The latter confer strength and extensibility to the cell wall and
      offer resistance for digestibility by ruminants. They also help blocking of the
      ingress of pathogens. The ester bound ferulic acid after oxidation in vivo
      generates reactive oxygen species that contribute to the fragmentation of non
      starch polysaccharides (hemicelluloses), and thereby reduces the product
      viscosity, a property seen during long-term storage of rice. In plant tissues,
      the arabinogalactans are implicated in such diverse functions as cell-cell
      adhesion, nutrition of growing pollen tubes, response to microbial infections,
      and also as markers of identity expressed in the terminal sequences of saccharide
      chains.

PMID- 11958335
TI  - Biotechnology of microbial xylanases: enzymology, molecular biology, and
      application.
AB  - Xylanases are hydrolases depolymerizing the plant cell wall component xylan, the
      second most abundant polysaccharide. The molecular structure and hydrolytic
      pattern of xylanases have been reported extensively and the mechanism of
      hydrolysis has also been proposed. There are several models for the gene
      regulation of which this article could add to the wealth of knowledge. Future
      work on the application of these enzymes in the paper and pulp, food industry, in
      environmental science, that is, bio-fueling, effluent treatment, and agro-waste
      treatment, etc. require a complete understanding of the functional and genetic
      significance of the xylanases. However, the thrust area has been identified as
      the paper and pulp industry. The major problem in the field of paper bleaching is
      the removal of lignin and its derivatives, which are linked to cellulose and
      xylan. Xylanases are more suitable in the paper and pulp industry than lignin
      degrading systems.

PMID- 11958337
TI  - Menthone and isomenthone biosynthesis in Pelargonium tomentosum Jacq.
AB  - Pelargonium tomentosum was fed with aqueous solutions of different deuterium
      labelled monoterpenoid precursors. After headspace extraction with solid phase
      microextraction (SPME) the essential oil was analyzed with enantioselective
      multidimensional gas chromatography/mass spectrometry (enantio-MDGC/MS). Labelled
      piperitone with different enantiomeric distributions led to labelled (-)
      isomenthone and labelled (+)-menthone in the same ratio as genuine (-)
      isomenthone and (+)-menthone. Furthermore, labelled pulegone, piperitenone,
      piperitole and citronellyl glycopyranoside were investigated.

PMID- 11958338
TI  - A conceptual model for forming surfaces with enantiomeric functionality from
      achiral molecules.
AB  - A means to form a surface with enantiomeric functionality using an achiral
      molecule is proposed. Specifically, if a meso compound were to be crystallized
      with the correct orientation, one set of opposing crystal faces would possess
      opposite handedness. This concept is a solid state analogue of a chromatographic
      device described previously.

PMID- 11958339
TI  - Enantiomeric enrichment of (+)-(3R,4S)-4-(4-fluorophenyl)-3-hydroxymethyl-1
      methylpiperidine by crystallization.
AB  - Two-fold crystallization of trans-4-(4-fluorophenyl)-3-hydroxymethyl-1
      methylpiperidine enriched in (+)-enantiomer 3b (65.2-79.4% ee) yielded the
      racemate that crystallized out of solution and the mother liquor highly enriched
      in 3b (95.4-97.6% ee). Differences in infrared spectra of the racemate and
      enantiomer proved that the racemate consists of a racemic compound. Furthermore,
      solution NMR spectra of enriched 3b showed differentiation of some resonances
      (self-induced non-equivalence), which indicated strong diastereomeric
      interactions between solutes in apolar solvent. The enantiomeric composition of
      products was determined by NMR spectroscopy in the presence of R-Mosher acid.

PMID- 11958340
TI  - A new approach toward the stereoselective synthesis of novel
      benzo[b][1,5]oxazepines using MCM-41(H) zeolite.
AB  - Facile procedures have been developed for the stereoselective synthesis of novel
      benzo[b][1,5]oxazepines 4a-f by the condensation reaction between 2-amino phenol
      2 and tert-butyl(4R)-2,2-dimethyl-4-(3-oxo-3-phenyl-1-propynyl)-1,3-oxazolane-3
      carboxylate 3a-f with MCM-41(H) zeolite in acetonitrile.

PMID- 11958341
TI  - Chiral synthesis and enzymatic resolution of (S)-(-)piperazine-2-carboxylic acid
      using enzyme alcalase.
AB  - Enantiomerically pure (S)-piperazine-2-carboxylic acid was synthesized by kinetic
      resolution of methyl-4-(tert-butyroxycarbonyl)-piperazine-2-carboxylate using a
      low cost enzyme alcalase.

PMID- 11958342
TI  - The molecular and crystal structure of (+/-)-1-methyl-7-oxa-norborn-5-ene
      2exo,3exo-dicarboxylic acid-anhydride and its enantiodifferentiation in 1H NMR
      spectroscopy.
AB  - The Diels-Alder reaction between 2-methylfuran and maleic anhydride leads to the
      formation of known racemic title adduct 3. The structure of this compound was
      confirmed by X-ray crystallography. An efficient enantiodifferentiation of 3 in
      1H NMR spectroscopy was observed upon treatment with Eu(hfc)3.

PMID- 11958343
TI  - The role of modifiers in high selectivity chiral separations on Pirkle-type
      columns.
AB  - Atypically high selectivity (alpha > 2) chiral separations have been observed on
      Pirkle type supports. These separations were examined in terms of their response
      to various modifiers, thermodynamic behavior and LSER modeling. Atypical
      thermodynamic and LSER results were observed along with large changes in
      selectivity between modifiers. The use of bulky modifiers gave increased
      selectivity resulting from dramatic increases in the retention of the second
      eluting enantiomer. These findings lead to the conclusion that increased
      retention is due to an inability of bulky modifers to penetrate a tight complex
      between selector and this enantiomer.

PMID- 11958344
TI  - Effect of theory-based feature correlations on typicality judgments.
AB  - In the present study, we examine what types of feature correlations are salient
      in our conceptual representations. It was hypothesized that of all possible
      feature pairs, those that are explicitly recognized as correlated (i.e., explicit
      pairs) and affect typicality judgments are the ones that are more likely theory
      based than are those that are not explicitly recognized (i.e., implicit pairs).
      Real-world categories and their properties, taken from Malt and Smith (1984),
      were examined. We found that explicit pairs had a greater number of asymmetric
      dependency relations (i.e., one feature depends on the other feature, but not
      vice versa) and stronger dependency relations than did implicit pairs, which were
      statistically correlated in the environment but were not recognized as such. In
      addition, people more often provided specific relation labels for explicit pairs
      than for implicit pairs; these labels were most often causal relations. Finally,
      typicality judgments were more affected when explicit correlations were broken
      than when implicit correlations were broken. It is concluded that in natural
      categories, feature correlations that are explicitly represented and affect
      typicality judgments are the ones about which people have theories.

PMID- 11958345
TI  - A further investigation of category learning by inference.
AB  - Categories are learned in many ways besides by classification, for example, by
      making inferences about classified items. One hypothesis is that classifications
      lead to the learning of features that distinguish categories, whereas inferences
      promote the learning of the internal structure of categories, such as the typical
      features. Experiment 1 included single-feature and full-feature classification
      tests following either classification or inference learning. Consistent with
      predictions, inference learners did better on the single tests but worse on the
      full tests. Experiment 2 further showed that inference learners, unlike
      classification learners, were no better at classifying items that they had seen
      at study compared with equally typical items they had not seen at study.
      Experiment 3 showed that features queried about during inference learning were
      classified better than ones not queried about, although even the latter features
      showed some learning on single-feature tests. The discussion focuses on how
      different types of category learning lead to different category representations.

PMID- 11958346
TI  - Generating alternatives: a key component in human reasoning?
AB  - According to mental models theory, a key aspect of deductive reasoning is the
      production of alternative models that can falsify provisional conclusions. In the
      present paper, the possibility is investigated that there are individual
      differences in the ability to produce alternative models. The results indicate
      that some people do not proceed beyond the first model when they reason with
      syllogisms but that others do. Furthermore, the ability to generate alternatives
      can be independently measured by asking participants to generate different
      representations of pairs of premises. These findings support the predictions of
      mental models theory and also indicate the potential importance of alternatives
      generation as a measure of individual differences in processing style.

PMID- 11958347
TI  - Relative informativeness of quantifiers used in syllogistic reasoning.
AB  - Three experiments tested a possible resolution of the probability heuristics
      model (PHM) of syllogistic reasoning proposed by Chater and Oaksford (1999), with
      their experimental results apparently showing that the generalized quantifier few
      was not as informative as suggested theoretically. Modifying the interpretation
      of few to take into account the distinction between positive and negative
      quantifiers (Moxey & Sanford, 1993) indicated two orderings over the quantifiers
      all, most, few, some, none, and some...not that are more consistent with the
      results. Experiments 1-3 tested these orderings empirically by having
      participants rank whether a quantifier applied to a particular probabilistic
      state of affairs. Experiments 1 and 2 showed that participants agreed on when a
      quantifier applied and that the empirically derived informativeness orderings
      were consistent with the proposed modifications of the order. Experiment 3 showed
      that this finding was robust even when response competition was eliminated.

PMID- 11958348
TI  - The influence of referential discourse context on modifier attachment in Dutch.
AB  - In an eye-tracking experiment we investigated the influence of referential
      context on the attachment of a relative clause to two possible hosts (as in
      "Someone shot the servant of the actress who was on the balcony"). The attachment
      of the relative clause was disambiguated grammatically at the first word after
      the onset of the ambiguity in order to investigate immediate effects of
      discourse. The contexts had been verified in a sentence completion study to make
      sure that they induced a strong bias toward early or late closure. The results of
      the reading experiment, however, revealed no significant interaction of
      referential context with the attachment preference of the relative clause. The
      only robust and consistent effect we found was a preference for early closure,
      independent of the preceding context. These data favor accounts positing that
      referential context does not influence the initial attachment decision, but does
      play a role in later phases of sentence processing.

PMID- 11958349
TI  - Comprehending anaphoric metaphors.
AB  - In this study we investigate the comprehension of various kinds of anaphoric
      metaphors in context. We describe an experiment that manipulated the
      metaphoricity of simple noun + verb + ending sentences by using either a
      metaphoric noun or a metaphoric verb or both. Our results show that metaphoric
      nouns affect sentence comprehension to a greater extent than do metaphoric verbs.
      Thus, even though there were no sentence-reading time differences between
      metaphoric and literal targets, metaphoric nouns were read more slowly than were
      literal nouns, and they also affected the reading time of the following verb.
      Moreover, in trials involving metaphoric-noun targets, participants read the
      endings of the targets faster and made more mistakes in answering posttrial
      questions than they did in literal-noun trials. We argue that these results
      suggest a comprehension deficit for anaphoric noun metaphors even when they are
      preceded by a context.

PMID- 11958350
TI  - Cross-modal re-mapping influences the Simon effect.
AB  - Tagliabue, Zorzi, Umilta, and Bassignani (2000) showed that one's practicing of a
      spatially incompatible task influences performance in a Simon task even when the
      interval between the two tasks is as long as 1 week. In the present study, three
      experiments were conducted to investigate whether such an effect could be found
      in a cross-modal paradigm, whereby stimuli in the two tasks were presented in
      different modalities. Subjects performed either compatible or incompatible
      mappings in an acoustic spatial compatibility task and, after an interval of 5
      min, 24 h, or 7 days, performed a visual Simon task. Results show that the
      spatially incompatible mapping task affected performance in the Simon task: The
      Simon effect was absent for all three intervals. This pattern is similar to the
      results of the Tagliabue et al. study, in which both tasks were performed in the
      same (visual) modality. Our findings disprove possible explanations based on
      episodic/contextual effects and support the hypothesis of a long-lasting spatial
      remapping that is not modality specific.

PMID- 11958351
TI  - Forward blocking depends on retrospective inferences about the presence of the
      blocked cue during the elemental phase.
AB  - When a compound cue AT is followed by an outcome (AT+), human participants will
      judge the relation between cue T and the outcome to be less strong if A alone was
      previously paired with the outcome (A+). According to the probabilistic contrast
      model, such a blocking effect is due to the fact that participants regard the A+
      trials as trials on which A and the outcome are present but T is absent. The
      results of two studies showed that when the status of T was ambiguous during the
      A+ trials, judgments about T depended on subsequent information about the
      presence of T during the A+ trials. These findings support the probabilistic
      contrast model but are incompatible with the (revised) Rescorla-Wagner (Rescorla
      & Wagner, 1972) model.

PMID- 11958352
TI  - The locus and nature of semantic congruity in symbolic comparison: evidence from
      the Stroop effect.
AB  - Pictures of animals with names of animals printed within the pictures were
      presented for comparative judgments of size based on either the pictures or the
      names. The picture-word compounds were compared faster with picture than with
      word as the relevant dimension. The comparisons of pictures were free of
      interference from the irrelevant names, but the comparisons of names suffered
      considerable Stroop interference from the irrelevant pictures. Large effects of
      semantic congruity characterized the comparisons of both pictures and words.
      Stroop congruity and semantic congruity did not interact even for comparison of
      words in which both were present, leading instead to additive effects. The
      results support theories that (1) place semantic congruity in the decision stage
      and (2) minimize the role of semantic processing as the basis of the semantic
      congruity effect.

PMID- 11958354
TI  - What information underlies correct rejections in short-term recognition memory?
AB  - We propose that correct rejections are based on information that contradicts the
      study set, rather than on insufficient familiarity. Using two-dimensional
      stimuli, we varied the featural overlap between lures and the study set so that
      one feature of the lure had occurred during study and the second feature of the
      lure had not occurred. Familiarity varied with the number of times the studied
      feature had occurred, whereas detectability of the extralist feature varied with
      the number of studied alternatives on the same dimension. Lures increased in
      difficulty with familiarity only when familiarity of the studied feature was
      confounded with the number of alternatives to the extralist feature. Hence, the
      difficulty in rejecting the lure was controlled by the number of alternatives to
      the extralist feature, not by the familiarity of the lure. Current theory
      requires additional representation assumptions and a new comparison process to
      accommodate these data.

PMID- 11958355
TI  - On predicting the future states of awareness for recognition of unrecallable
      items.
AB  - Two experiments were conducted that examined people's predictive accuracy for
      their future states of awareness. In both experiments, participants learned word
      pairs and were tested with a cued recall test. When recall failed, predictive
      judgments were obtained. In Experiment 1, feeling of knowing judgments predicted
      not only future recognition but also the state of awareness as remembered or
      known that was associated with that recognition. In Experiment 2, predictive
      remember-know judgments were found to be accurately diagnostic of future states
      of awareness as well. One conclusion to be drawn from these data is that
      recollective details are among the partial knowledge that is retrieved in the
      absence of successful cued recall. General implications for theories of feeling
      of knowing are discussed.

PMID- 11958353
TI  - Is the go/no-go lexical decision task an alternative to the yes/no lexical
      decision task?
AB  - In the go/no-go lexical decision task (LDT), participants are instructed to
      respond as quickly as they can when a word is presented and not to respond if a
      nonword is presented. By minimizing part of the response selection process in the
      experimental task, the impact of response decision time on the obtained lexical
      decision time is probably reduced relative to the standard yes/no LDT (Gordon,
      1983). Experiments 1 and 2 show that the go/no-go LDT is sensitive to the effects
      of word frequency and associative priming--the magnitude of these effects is
      similar with the two tasks. More important, the go/no-go LDT has a number of
      advantages with respect to the "standard" yes/no LDT: It offers faster response
      times, more accurate responding, and fewer processing demands than does the
      yes/no task. Accordingly, the go/no-go task appears to be an excellent
      alternative to the standard yes/no task.

PMID- 11958356
TI  - Strong cues are not necessarily weak: Thomson and Tulving (1970) and the encoding
      specificity principle revisited.
AB  - Performance on tests in which there is control over reporting (e.g., cued recall
      with the option to withhold responses) can be characterized by four parameters:
      free- and forced-report retrieval (correct responses retrieved from memory when
      the option to withhold responses is exercised and when it is not, respectively),
      monitoring (discrimination between correct and incorrect potential responses),
      and report bias (willingness to report responses). Typically, researchers do not
      examine all these components in cued-test performance; blanks are sometimes
      counted the same as errors, meaning that the (free-report) performance index is
      contaminated with report bias and monitoring ability. In this research, a two
      stage testing procedure is described that allows measures of free- and forced
      report retrieval, monitoring, and bias to be derived from the original encoding
      specificity experiments (Thomson & Tulving, 1970). The results show that their
      cue-reinstatement manipulation affected free-report retrieval, but once report
      bias and monitoring effects were removed by forcing output, retrieval was
      unaffected.

PMID- 11958357
TI  - The sandwich effect reassessed: effects of streaming, distraction, and modality.
AB  - The degree of disruption from interleaving auditory irrelevant items within a
      sequence of to-be-remembered items--the sandwich effect--was examined in two
      experiments. Previous demonstrations of the effect have shown that the penalty
      for interleaving items is small and that changing irrelevant tokens is no more
      damaging than repeating ones (contrary to the classic changing state effect of
      irrelevant sound). The results of Experiment 1 suggest that these earlier results
      were due to the lack of tokens in the irrelevant sequence (in part, the result of
      using a span method). The results of Experiment 2 also show that the sandwich
      effect was marked and, further, that it comprised two elements, one due to the
      partitioning of relevant from irrelevant streams (which may be promoted by
      similarity of identity within sequence or pitch disparity between sequences), and
      the other a classic irrelevant sound effect (with effects of changing state). The
      results are discussed in terms of the role of perceptual organization within and
      between modalities in short-term memory.

PMID- 11958358
TI  - Top-down processing and the suffix effect in young and older adults.
AB  - The suffix effect has generally been viewed as reflecting an automatic component
      involving the terminal item and a component susceptible to top-down influences
      involving the preterminal items (Balota & Engle, 1981). Recent findings have
      raised questions about this widely accepted view of the suffix effect by showing
      that the terminal component is not insensitive to top-down influences (Bloom &
      Watkins, 1999). In the present study, we attempted to uncover the source of these
      contradictory findings by assessing whether the terminal item's susceptibility to
      top-down influences might depend on subjects' first-hand experience of the extent
      to which recall is affected by the suffix. Furthermore, we examined whether age
      differences in the suffix effect could be attributed to age-related declines in
      inhibitory processes. Our findings supported both predictions.

PMID- 11958359
TI  - A multidimensional scaling approach to mental multiplication.
AB  - Adults consistently make errors in solving simple multiplication problems. These
      errors have been explained with reference to the interference between similar
      problems. In this paper, we apply multidimensional scaling (MDS) to the domain of
      multiplication problems, to uncover their underlying similarity structure. A tree
      sorting task was used to obtain perceived dissimilarity ratings. The derived
      representation shows greater similarity between problems containing larger
      operands and suggests that tie problems (e.g., 7 x 7) hold special status. A
      version of the generalized context model (Nosofsky, 1986) was used to explore the
      derived MDS solution. The similarity of multiplication problems made an important
      contribution to producing a model consistent with human performance, as did the
      frequency with which such problems arise in textbooks, suggesting that both
      factors may be involved in the explanation of errors.

PMID- 11958360
TI  - Topiramate treatment of bipolar spectrum disorders: a retrospective chart review.
AB  - The objective of this paper was to determine if topiramate is effective as
      treatment for bipolar spectrum disorders in a naturalistic setting. All charts of
      outpatients treated with topiramate (n = 76) were reviewed, and clinical response
      was assessed retrospectively using the Clinical Global Impressions Scale for
      Improvement. Mild improvement was seen in 47% (n = 36) and moderate-to-marked
      improvement in 13% (n = 10). Responders received a higher mean dose (180 mg/day)
      than did nonresponders (83.2 mg/day, p = 0.002). Topiramate dose was also higher
      in those who lost weight (138.3 mg/day) than in those who did not (70 mg/day, p =
      0.007). Weight loss was experienced by 50% of the sample, with a mean loss of
      14.2 lbs. Side effects were reported by 82% (n = 62) of the population, including
      cognitive effects, sedation, parasthesias, nausea, insomnia, headache, and
      dizziness. Adverse effects led 36% (n = 27) of the total sample to discontinue
      treatment with topiramate. Topiramate led to significant weight loss in about
      half of this bipolar population, while also improving mood symptoms at least
      mildly in most patients. Topiramate response and weight loss were both dose
      related, with efficacy, in particular, associated with higher doses (mean = 180
      mg/day) than frequently used in current clinical practice.

PMID- 11958361
TI  - Outcome of self-reported functional-somatic symptoms in a community sample of
      adolescents.
AB  - It is unclear if functional-somatic symptoms in adolescents increase the risk for
      future psychiatric disorders. Therefore, the outcome and continuity of adolescent
      self-reported functional-somatic symptoms in young adulthood were assessed. Self
      reported data on functional-somatic symptoms from an ongoing epidemiological
      study in children started in 1983 were analyzed. Participants were adolescents
      aged 11-18 who filled out standardized questionnaires in 1989 and 1991 and who
      were reassessed in 1997 when they were young adults between ages 19 and 26.
      Outcome measures were research psychiatric diagnoses and self-reported functional
      somatic symptoms in 1997. Functional-somatic symptoms were associated with other
      measures of psychopathology in adolescents. Adolescents with specific functional
      somatic symptoms tended to report the same symptom along with other symptoms at
      follow-up. Adolescent self-reported functional-somatic symptoms did not increase
      the risk for future psychiatric disorders. Young adults with functional-somatic
      complaints were diagnosed more often than controls with depressive disorders and
      anxiety disorders, but not with antisocial personality disorders and substance
      use disorders. Adolescent self-reported functional-somatic symptoms were common
      and enduring but were not predictive for psychiatric disorders in young
      adulthood. Adolescents and young adults who complain of multiple functional
      somatic complaints should be assessed for the presence of a psychiatric disorder
      particularly depression or anxiety.

PMID- 11958362
TI  - Use of olanzapine for elderly patients with psychotic disorders: a review.
AB  - The number of elderly persons with psychosis will increase with the increasing
      geriatric population. Olanzapine is one of the newer atypical antipsychotics with
      efficacy for positive and negative symptoms and safer side effect profile
      compared to conventional antipsychotics. The manuscript describes the
      pharmacology, efficacy and tolerability studies, adverse effects and dosing
      considerations in the elderly. Further studies are needed to fully assess the
      efficacy and safety of olanzapine in the elderly. Current research supports a
      role for olanzapine in treating elderly patients with schizophrenia,
      schizoaffective disorder and behavioral and psychological symptoms of dementia.

PMID- 11958363
TI  - Iatrogenic disorders associated with conventional vs. atypical antipsychotics.
AB  - Pharmacotherapy is an indispensable component of the management of schizophrenia
      and related psychotic disorders. Antipsychotic drugs are used for their efficacy
      in controlling the symptoms of psychosis. However, the side effects of
      antipsychotic drugs can have a deleterious impact on the course of the illness by
      inducing iatrogenic symptoms of various severity. The side effects of first
      generation or conventional antipsychotic drug were often so intolerable to
      patients with schizophrenia that their compliance was consistently poor, leading
      to frequent relapse, chronicity, and impaired functioning. The second-generation
      (atypical) antipsychotics, introduced 40 years after the advent of the older
      generation, are proving to have better outcomes in psychosis not only because of
      broader symptom efficacy but also because their side-effect profile is more
      tolerable, leading to higher compliance and fewer relapses. The authors review
      the side effects of the old and the new antipsychotics and conclude that the
      improved tolerability of the new antipsychotics is associated with greater
      effectiveness, not just efficacy. Differences in tolerability among the new
      antipsychotics are described.

PMID- 11958364
TI  - A case of kleptomania and compulsive sexual behavior treated with naltrexone.
AB  - Objective of this paper was to examine a possible treatment option for two
      disorders currently lacking agreed upon pharmacotherapeutic interventions. We
      report a patient fulfilling DSM-IV criteria for kleptomania with comorbid
      compulsive sexual behavior who failed to respond to fluoxetine, behavioral
      therapy, and psychotherapy, and who was therefore treated with naltrexone to
      reduce urges to steal and sexual urges. Treatment with high-dose naltrexone (150
      mg/day) led to remission of both the patient's urges to steal and sexual urges.
      Discontinuation and rechallenge with the medication provides further support that
      improvement was due to naltrexone. Naltrexone in high doses show promise for the
      treatment of both kleptomania and compulsive sexual behavior.

PMID- 11958365
TI  - Initiation of clozapine therapy in a patient with preexisting leukopenia: a
      discussion of the rationale of current treatment options.
AB  - Clozapine remains the most effective agent for diminishing or eliminating
      psychotic symptoms in treatment-resistant patients. However, among such patients,
      a small percentage (<3.0%) develops clozapine-induced granulocytopenia (CIG). In
      spite of the fact that lithium and granulocyte colony stimulating factor (G-CSF)
      have been shown to reverse CIG, many such patients are consigned to treatment
      with antipsychotic agents that have failed in the past. Apparently, their
      physicians are not aware that these patients can be salvaged for ongoing
      clozapine treatment. We report the effectiveness of lithium in reversing CIG in a
      young man with preexisting mild granulocytopenia. The rapidity of onset of
      leukocyte depletion is discussed in light of previously hypothesized autoimmune
      mechanisms of CIG. This case dramatizes the importance of lithium (or G-CSF)
      augmentation in those patients to maintain clozapine treatment so that their
      neutropenia can be reversed, and they can continue to benefit from the unique
      antipsychotic qualities of clozapine.

PMID- 11958366
TI  - Customer, client, consumer, recipient, or patient.
AB  - Since the arrival of managed care, there has been a trend toward changing the
      basic terminology used to address clinicians and patients. Instead of the term
      "patient", third party payors frequently use terms such as "customer, client,
      consumer or recipient". One study demonstrated that patients prefer to be called
      patients. To investigate the preferred term to refer to patients and to be
      referred to by patients, we mailed a questionnaire to 100 physicians in four
      medical specialties each and to 100 psychologists. The overall response rate was
      61%. Physicians overwhelmingly preferred to refer to patients by the patient's
      last name, their second preference was the patient's first name. Psychologists
      preferred to refer to the patients by first name, their second preference was the
      patient's last name. No group favored using terms such as client, customer,
      consumer, or recipient. Most physicians and psychologists preferred being
      referred to as doctors and nobody favored the term provider.

PMID- 11958367
TI  - Glucose metabolism, schizophrenia, and antipsychotic drugs: comments to the paper
      of Dwyer et al.

PMID- 11958368
TI  - Allelic gain and amplification on the long arm of chromosome 17 in anaplastic
      meningiomas.
AB  - Using comparative genomic hybridization (CGH) we have previously identified
      amplification at 17q21-qter as a common aberration in anaplastic meningiomas but
      not in atypical or benign meningiomas (19). To define the amplified genomic
      region, we analyzed 44 meningeal tumors, including 7 benign meningiomas of World
      Health Organization (WHO) grade 1,19 atypical meningiomas (WHO grade II) and 18
      anaplastic meningiomas (WHO grade III) at 46 chromosome 17 loci (including 42 17q
      loci). In line with the CGH data we found evidence of increased numbers of
      alleles on 17q. The incidence rose with malignancy grade, culminating at 61% (11
      of 18 cases) in the anaplastic meningioma group. The majority of cases showing
      increased allele numbers had, on average, low-level allelic gains (relative
      increase in allele dosage of 2- to 5-fold). Amplification of alleles (defined
      here as an average relative increase in allele dosage of more than 5 times) was
      detected in 2 anaplastic meningiomas. The amplification patterns in these tumors
      defined a number of common regions of amplification/increased allele copy number,
      the best defined include one between D17S790 and D17S1607 and one between
      D17S1160 and PS6K. Real-time PCR analysis of the PS6K candidate gene revealed no
      high-level amplification despite this affecting adjacent loci. Our findings are
      fundamental for the identification of the gene(s) in 17q22-q23 that is (are) the
      target(s) for increased copy number in anaplastic meningiomas and possibly other
      tumor types.

PMID- 11958369
TI  - Abnormal endothelial tight junctions in active lesions and normal-appearing white
      matter in multiple sclerosis.
AB  - Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is
      characteristic of new and expanding inflammatory lesions in relapsing-remitting
      and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in
      primary progressive MS. However, the anatomical route(s) of BBB leakage have not
      been demonstrated. We investigated the possible involvement of interendothelial
      tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO
      1 ) in blood vessels in active MS lesions from 8 cases of MS and in normal
      appearing white (NAWM) matter from 6 cases. Blood vessels (10-50 per frozen
      section) were scanned using confocal laser scanning microscopy to acquire
      datasets for analysis. TJ abnormalities manifested as beading, interruption,
      absence or diffuse cytoplasmic localization of fluorescence, or separation of
      junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red
      O-positive active plaques but less frequent in NAWM (15%), and in normal (< 2%)
      and neurological controls (6%). Putatively "open" junctions were seen in vessels
      in active lesions and in microscopically inflamed vessels in NAWM. Dual
      fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein
      leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB
      leakage in enhancing MRI lesions and may also be involved in subtle leakage in
      non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight
      junctional pathology should be regarded as a significant form of tissue injury in
      MS, alongside demyelination and axonopathy.

PMID- 11958370
TI  - The expression profile of myogenic transcription factors in satellite cells from
      denervated rat muscle.
AB  - The muscle-specific transcription factors of the MyoD family are altered after
      denervation. In order to determine whether this shift takes place in satellite
      cells (SC), we investigated the expression pattern of MyoD, myf5, myogenin, and
      MRF4 in SC. Hindlimb muscles of rats were denervated for 2 days to 4 weeks. SC
      were isolated, pooled and the transcription of all 4 factors was assessed by RT
      PCR. Protein expression was assessed in histological sections of soleus and
      anterior tibial (TA) muscles; SC were identified by M-cadherin. Pooled SC from
      innervated muscles expressed myf5 mRNA, and very weakly MyoD and myogenin mRNA.
      MyoD and myogenin protein was found in only few SC. After denervation, pooled SC
      expressed myf5 mRNA, and very weakly myogenin and MRF4 mRNA. Myogenin protein was
      found in less than about 10% of the cells, whereas MRF4 protein was absent from
      SC. We conclude that the presence of myf5 and the absence of MyoD and MRF4
      protein in SC after denervation indicated the quiescent state of the cell cycle.
      A subset of SC has additionally acquired myogenin. SC after denervation might be
      less easily recruited into the mitotic cycle than SC from normal muscle,
      rendering regeneration of denervated muscle less efficient than normal muscle.

PMID- 11958371
TI  - Novel PLA2G4C polymorphism as a molecular diagnostic assay for 19q loss in human
      gliomas.
AB  - PLA2G4C, encoding cytosolic phospholipase A2-gamma (cPLA2-gamma), is a 17-exon
      gene located on chromosome 19q13.3 within the putative glioma tumor suppressor
      gene region. Given the clinical importance of assessing 1p and 19q loss in human
      gliomas, the development of convenient and practical assays for detecting allelic
      loss is of considerable priority in neuro-oncology. We report a minisatellite
      polymorphism in the untranslated region of exon 1, with allelic variants that
      have one, two or three 27-bp repeats. The polymorphism is informative in 55.7% of
      a reference population, and accurately detects allelic loss of 19q in human
      gliomas. This novel marker offers distinct advantages for assessing 19q status in
      malignant gliomas. The relatively large size of the repeats allows detection of
      allelic variants with standard ethidium bromide-stained agarose gels and the
      PLA2G4C marker is the closest polymorphism to the smallest common deletion area
      in the putative glioma tumor suppressor gene region. These characteristics
      suggest that the PLA2G4C polymorphism will be a convenient and practical assay
      for clinical and research evaluation of 19q status in human gliomas.

PMID- 11958374
TI  - Epilepsy: disease and model to study human brain function.

PMID- 11958372
TI  - A role for chromosome 9p21 deletions in the malignant progression of meningiomas
      and the prognosis of anaplastic meningiomas.
AB  - Meningiomas display significant variability in terms of recurrence and survival
      rates, even within tumor grade. Although several recent modifications of the
      grading system have improved our ability to predict biologic behavior, additional
      prognostic markers are needed. Inactivation of the cell cycle regulator, p16
      (CDKN2A), has recently been observed in a small subset of atypical and the
      majority of anaplastic meningiomas. To assess the potential clinical utility of
      this marker, we performed dual-color FISH on 117 well-characterized archival
      meningiomas using paired commercial probes to the chromosome 9 centromeric (CEP9)
      and p16 (9p21) regions. Benign meningiomas (N = 42) were divided into non
      recurring versus recurring groups. Atypical meningiomas (N = 52) consisted of
      proliferative and brain invasive subsets. The 23 anaplastic meningiomas were not
      further stratified. Deletion of p16 or monosomy 9 was seen in 17% of benign, 52%
      of atypical, and 74% of anaplastic meningiomas (p < 0.001). No statistically
      significant differences were found among subsets of benign or subsets of atypical
      meningioma, though there were more recurrences in those with deletion. Despite
      potential effects on cell cycle regulation, p16 deletions were not restricted to
      meningiomas with a high proliferative index. Most importantly, p16 deletion was
      strongly associated with survival in the anaplastic meningioma cohort, with a
      risk ratio for death of 6.79 (p = 0.016). Conversely, absence of deletion
      identified a subset of anaplastic meningioma patients (26%) with prolonged
      survival. We conclude that chromosome 9p21 deletions are associated with
      malignant progression of meningiomas and poor prognosis in anaplastic
      meningiomas.

PMID- 11958375
TI  - Ammon's horn sclerosis: a maldevelopmental disorder associated with temporal lobe
      epilepsy.
AB  - Ammon's horn sclerosis (AHS) is the major neuropathological substrate in patients
      with temporal lobe epilepsy (TLE). Histopathological hallmarks include segmental
      loss of pyramidal neurons, granule cell dispersion and reactive gliosis.
      Pathogenetic mechanisms underlying this distinct hippocampal pathology have not
      yet been identified and it remains to be resolved whether AHS represents the
      cause or the consequence of chronic seizure activity and pharmacoresistant TLE.
      Whereas the clinical history indicates an early onset in most patients, ie,
      occurrence of febrile seizures at a young age, surgical treatment is usually
      carried out at an end stage of the disease. It has, therefore, been difficult to
      analyse the sequential development of hippocampal pathology in TLE patients.
      Recent molecular neuropathological studies focusing on developmental aspects of
      hippocampal organization revealed 2 intriguing findings in AHS specimens: i) The
      persistence of Cajal-Retzius cells in AHS patients points towards an early insult
      and an altered Reelin signaling pathway and ii) increased neurogenesis in and
      abnormal architectural organization of the dentate granule cell layer can be
      observed in young patients with early hippocampal seizure onset. These findings
      would be compatible with a model that involves a neurodevelopmental component in
      the formation of AHS. Its association with a lowered seizure threshold and an
      increased susceptibility for segmental cell loss in the hippocampus during the
      long course of the disease may constitute additional elements in a pathogenic
      cascade.

PMID- 11958376
TI  - Neurodevelopmental disorders as a cause of seizures: neuropathologic, genetic,
      and mechanistic considerations.
AB  - This review will consider patterns of developmental neuropathologic abnormalities
      malformations of cortical development (MCD)--encountered in infants (often with
      infantile spasms), children, and adults with intractable epilepsy. Treatment of
      epilepsy associated with some MCD, such as focal cortical dysplasia and tubers of
      tuberous sclerosis, may include cortical resection performed to remove the
      "dysplastic" region of cortex. In extreme situations (eg, hemimegalencephaly),
      hemispherectomy may be carried out on selected patients. Neuropathologic
      (including immunohistochemical) findings within these lesions will be considered.
      Other conditions that cause intractable epilepsy and often mental retardation,
      yet are not necessarily amenable to surgical treatment (eg, lissencephaly,
      periventricular nodular heterotopia, double cortex syndrome) will be discussed.
      Over the past 10 years there has been an explosion of information on the genetics
      of MCD. The genes responsible for many MCD (eg, TSC1, TSC2, LIS-1, DCX, FLN1)
      have been cloned and permit important mechanistic studies to be carried out with
      the purpose of understanding how mutations within these genes result in abnormal
      cortical cytoarchitecture and anomalous neuroglial differentiation. Finally,
      novel techniques allowing for analysis of patterns of gene expression within
      single cells, including neurons, is likely to provide answers to the most vexing
      and important question about these lesions: Why are they epileptogenic?

PMID- 11958377
TI  - "Epileptic neurons" in temporal lobe epilepsy.

PMID- 11958379
TI  - What is an oligodendroglioma?

PMID- 11958380
TI  - International Society of Neuropathology Outreach Program.

PMID- 11958378
TI  - Animal models of limbic epilepsies: what can they tell us?
AB  - In this review, we have provided an overview of the implementation and
      characteristics of some of the most prevalent models of temporal lobe epilepsy in
      use in laboratories around the world today. These include spontaneously seizing
      models with status epilepticus as the initial precipitating injury (including the
      kainate, pilocarpine, and electrical stimulation models), kindling, and models of
      drug refractoriness. These models share various features with one another, and
      also differ in many aspects, providing a broader representation of the full
      spectrum of clinical limbic epilepsies. We have also provided a brief
      introduction into how animal models of temporal lobe epilepsy facilitate use of
      modern state-of-the-art techniques in neurobiology to address critical questions
      in the pathogenesis of epilepsy.

PMID- 11958381
TI  - October 2001: 40-year-old Xhosa male with back pain and leg weakness.
AB  - A 40-year-old Xhosa male presented with progressive upper lumbar back pain and
      weakness At examination he was emaciated and had enlarged lymph nodes in the
      groin and axilla. Both lower limbs were severely atrophic and weak. Sensation to
      touch and pain was decreased below L3 bilaterally. MR of the spine showed a
      discrete, contrast-enhancing epidural mass. A T10-T12 laminectomy revealed an
      soft, vascular extradural tumor dorsal to the cord. The mass was loosely applied
      to the dura and easy to remove. The operative specimen consisted of a sausage
      shaped (3.5 x 2.0 x 1.2 cm), thinly-encapsulated mass of reddish-brown tissue.
      The cut surface had a mottled, vaguely nodular, yellowish-brown appearance.
      Microscopic examination revealed sheets of hematopoeitic elements, including
      myeloid, red cell and megakaryocytic lines, the latter showing Factor 8-related
      positivity. The final diagnosis was extramedullary hematopoiesis (EMH). A bone
      marrow biopsy performed as a result of the diagnosis showed a myeloproliferative
      disease and polycythemia vera. EMH in the spinal epidural space is a rare but
      treatable cause of progressive paraparesis in patients with a variety of
      hematological disorders. Since 1956 there have been more than 50 reported cases,
      most of which occurred in association with thalassaemia. In spinal cord
      compression secondary to EMH, the lesions are commonly localized to the mid-lower
      thoracic region.

PMID- 11958382
TI  - November 2001: 67-year-old man in coma requiring prolonged mechanical
      ventilation.
AB  - A 67-year-old man was found to have massive pituitary necrosis occupying
      approximately 85% of the anterior lobe after being supported with mechanical
      ventilation for 35 days. The findings were compatible with "respirator pituitary"
      found in mechanically ventilated patients. The lesions represent coagulative
      infarctions due to ischemia. The role of the respirator is believed to be buying
      time to allow the changes to develop.

PMID- 11958383
TI  - December 2001: rapidly progressive motor weakness, starting in pregnancy.
AB  - A 25-year-old woman presented with rapidly progressive motor weakness
      necessitating ventilation 10 months after the onset. Despite immunosuppressive
      therapy she died 27 months later, without developing significant extramotor
      features. Autopsy revealed evidence of both upper and lower motor neuron loss
      with wide-spread motor and extramotor intraneuronal basophilic inclusions, most
      of which did not show ubiquitin immunoreactivity. Motor neuron disease with
      basophilic inclusions appears to be a rare, but distinctive pathological subtype,
      with most reported cases occurring sporadically in young women and having a rapid
      clinical progression.

PMID- 11958384
TI  - Reproducibility of skin microcirculatory measurements in humans, with special
      emphasis on capillaroscopy.
AB  - The reproducibility of capillaroscopic measurements of capillary blood cell
      velocity (CBV) in human nailfolds was investigated by use of the computerized
      system CapiFlow. Therefore, CBV measurements of two capillaries of each of three
      fingers together with laser Doppler fluxmetry (LDF) and skin temperature
      measurements were performed three times in five healthy volunteers. Short-term
      (1.5 h) intra-individual coefficient of variation (CV) of CBV was 18.4%. Long
      term (7 days) CV amounted to 55.8%. Inter-individual CV was 55.9%. Short- and
      long-term intra-individual CVs of LDF were 25.4% and 37.3%. Inter-individual
      variation was 36.0%. Skin temperature showed short- and long-term CVs of 3.7% and
      5.5% and inter-individual CV of 5.8%. In conclusion, measurement of CBV using
      CapiFlow is a suitable method to assess acute effects, but has limited value in
      investigating long-term effects. Because of the wide interindividual variability
      in both CBV and LDF, power calculations will reveal large numbers to investigate.
      Skin temperature has a relatively small intra- and inter-individual variation and
      is more suitable for long-term studies.

PMID- 11958385
TI  - Small and large artery elasticity indices in peripheral arterial occlusive
      disease (PAOD).
AB  - In peripheral arterial occlusive disease (PAOD), arterial compliance of the
      central arteries has been reported to be reduced. It is, however, not clear
      whether, in PAOD, decreased arterial compliance is also accompanied by similar
      changes in the peripheral arteries. Therefore the aim of the study was to
      determine the large (C1) and small (C2) artery elasticity indices in PAOD and
      their relations to its well-accepted characteristics (ankle-brachial index, ABI;
      pulse pressure, PP; absolute claudication distance, ACD). A total of 43 patients
      with PAOD (mean age 68 +/- 9 years; ABI of the limiting leg 0.65 +/- 0.14; SBP
      (systolic blood pressure) 149 +/- 20 mmHg, and ACD 488 +/- 187 m) were enrolled
      as well as 16 control subjects of comparable age (69 +/- 4 years) and blood
      pressure (SBP 147 +/- 27 mmHg). All subjects underwent non-invasive pulse wave
      analysis in order to determine arterial compliance of the aorta and major side
      branches (C1) and of the distal circulation (C2), using a modified Windkessel
      model. In PAOD, both C1 (1.41 +/- 0.56 ml/mmHg) and C2 (0.023 +/- 0.012 ml/mmHg)
      were comparable to values in an age and blood pressure-matched control group (C1,
      1.25 +/- 0.66 ml/mmHg; C2, 0.027 +/- 0.008 ml/mmHg). C1 was significantly
      correlated with ACD (r = 0.36, p = 0.02), PP (r = -0.33, p < 0.02) and only
      borderline with ABI (r = 0.28, p = 0.07). C2 was correlated with PP (r = -0.38, p
      < 0.01), ABI (r = 0.36, p < 0.02) but not with ACD. Large (C1) and small (C2)
      artery elasticity indices in PAOD were decreased but comparable to values in an
      elderly group with isolated systolic hypertension. Moreover, C1 and C2 correlated
      with markers (ABI and PP) of severity of vascular disease.

PMID- 11958386
TI  - Comparison of two progressive treadmill tests in patients with peripheral
      arterial disease.
AB  - In a vascular rehabilitation program, 28% of our frail elderly patients are
      unable to be tested with traditional progressive exercise protocols at program
      entry due to the high (2.0 miles/h or 3.2 km/h) initial treadmill speeds. The
      purpose of this investigation was to compare a new progressive treadmill protocol
      which has a reduced initial speed (1.0 mile/h or 1.6 km/h) to an established
      protocol performed at 2.0 miles/h (3.2 km/h) to determine the comparability and
      reproducibility of the new protocol. Eleven patients with arterial claudication
      performed three symptom-limited exercise tests in random order. Two tests used
      the new protocol while the remaining trial used the established protocol.
      Claudication pain was measured using a 5-point scale. Oxygen consumption, heart
      rate, minute ventilation, respiratory exchange ratio and blood pressure at peak
      exercise were similar among the three trials. There were strong intraclass
      correlations for peak oxygen consumption (r = 0.97), onset of claudication (r =
      0.96) and maximum walking time (r = 0.98) between the two trials using the new
      protocol. There was also a significant correlation between the new protocol and
      the established protocol for peak oxygen consumption (r = 0.90) and maximum
      walking time (r = 0.89). The new progressive treadmill protocol represents a
      valid, reliable protocol for patients with arterial claudication. This protocol
      may be useful for testing patients with a low functional capacity so that
      clinically appropriate exercise prescriptions can be established and the efficacy
      of treatments can be determined.

PMID- 11958387
TI  - The relationship between history of falling and physical function in subjects
      with peripheral arterial disease.
AB  - The purpose of this study was to determine whether peripheral arterial disease
      (PAD) subjects with a history of falling had more impaired physical function than
      their non-falling counterparts. A total of 120 PAD subjects (26%) who had fallen
      over the past year and 346 PAD subjects (74%) who had not fallen were evaluated.
      Additionally, subjects were characterized on physical function, consisting of
      balance, strength, ambulatory function, and monitored physical activity, as well
      as PAD-specific measures of ankle/brachial pressure index (ABPI) and treadmill
      claudication distances. Full-tandem stance time was 19% shorter (p < 0.001) in
      the fallers than in the non-fallers (7.2 +/- 0.3 vs 8.9 +/- 0.1 s; mean +/- SEM),
      and the self-reported ability to climb stairs was 36% lower (27 +/- 4 vs 42 +/-
      2%). Furthermore, the fallers were 126% more likely (p < 0.001) to report
      ambulatory stumbling and unsteadiness, took 14% longer (p = 0.022) to perform
      five sequential sit-to-stand transfers using an armless chair, covered 16%
      shorter distance (p < 0.001) during a 6-min walk test, and were 25% less
      physically active than the non-fallers. The groups had similar ABPI and treadmill
      claudication distances (p < 0.05). A history of falling was independently related
      to the self-reported ability to climb stairs, the full-tandem stance time, self
      reported ambulatory stumbling and unsteadiness, and daily physical activity
      (multiple R = 0.47, p < 0.001). In conclusion, impairments in multiple domains of
      physical function were associated with a history of falling in PAD subjects with
      intermittent claudication. Furthermore, the link between poor physical function
      and falling was independent of PAD severity.

PMID- 11958388
TI  - Peripheral arterial disease and depressed mood in older men and women.
AB  - The objective of this study was to determine whether lower extremity peripheral
      arterial disease (PAD) is associated with depressive symptoms and whether PAD
      related disability mediates the association between PAD and depressive symptoms.
      The study used a cross-sectional design set in an academic medical center. A
      cohort of men and women aged 55 years and older with (n = 93) or without (n = 74)
      PAD was recruited. PAD subjects were identified from a blood flow laboratory and
      a general medicine practice. Non-PAD subjects were identified from the same
      general medicine practice. PAD was diagnosed and quantified using the ankle
      brachial index (ABI). Depressive symptoms were assessed by the 15-item short
      version of the Geriatric Depression Scale (GDS-S; score range 0-15, 0 = no
      depressive symptoms). The six-minute walk test and the Walking Impairment
      Questionnaire (WIQ) distance score (score range 0-100, 100 = better walking
      ability) were measures of walking impairment. PAD subjects had depressive mood
      (DM) (defined by GDS-S score >5) twice as often as controls (24% vs 12%, p =
      0.06). After adjustment for age, education, and number of comorbidities, the
      prevalence of depressive mood among PAD subjects was increased, but this
      association was not significant (OR = 1.8, 95% CI 0.7-4.4). The WIQ distance
      score weakened the association between PAD and DM, and higher distance scores
      were associated with a lower likelihood of DM (OR = 0.98 per one unit of the WIQ,
      95% CI 0.96-0.99). Among PAD subjects, severe PAD (ABI <0.5) was not
      significantly associated with DM (OR = 1.4, 95% CI 0.5-4.1), but a greater 6-min
      walk distance was associated with a lower likelihood of DM (OR = 0.8 per 100
      feet, 95% CI 0.70-0.97). Substituting the WIQ scores for six-min walk distance in
      the model showed that higher WIQ scores were associated with lower likelihood of
      DM among PAD subjects (OR= 0.98 per one unit of the WIQ, 95% CI 0.95-1.0), though
      the association did not achieve statistical significance. In conclusion, these
      data suggest that PAD may be associated with an increased risk of DM and that
      this relationship may be related to PAD-associated disability. An evaluation for
      depression may be appropriate in men and women with PAD. Findings should be
      evaluated in a larger study cohort.

PMID- 11958389
TI  - Proteinuria in a placebo-controlled study of basic fibroblast growth factor for
      intermittent claudication.
AB  - Intermittent claudication is the most common symptom of peripheral arterial
      disease (PAD), in part due to an inadequate rise in limb blood flow with
      exercise. Claudication causes a severe impairment in functional capacity and
      quality of life in over 3 million Americans. Basic fibroblast growth factor
      (bFGF) stimulates angiogenesis in vivo and improves limb blood flow in several
      animal models of hindlimb ischemia. However, the relative safety and efficacy of
      angiogenic molecules in the treatment of claudication has not been fully
      evaluated in prospective, blinded clinical trials. In this study, a randomized,
      double-blind, placebo-controlled, phase II trial of recombinant human bFGF for
      the treatment of intermittent claudication was performed. bFGF was administered
      weekly by intravenous infusions of 2 microg/kg for 6 sequential weeks (total dose
      12 microg/kg). The primary efficacy endpoint was change in peak walking time
      (PWT) on a graded exercise treadmill protocol. Secondary efficacy endpoints
      included changes in functional status as measured by validated questionnaires.
      The study was stopped prematurely after treatment of the first 24 subjects due to
      proteinuria in five of the 16 subjects who received systemic bFGF, which exceeded
      1000 mg/24 h in four of these five subjects. The small sample size limited
      evaluation of the predefined efficacy endpoints; however, there was no
      significant difference between the treatment and control groups for any of the
      measures of efficacy. In conclusion, intravenous administration of bFGF delivered
      at low doses weekly for 6 weeks was associated with a high rate of severe
      proteinuria. It is speculated that bFGF-related proteinuria in this study was
      primarily related to the systemic route of administration and the frequent dosing
      schedule. Future clinical trials of bFGF protein should carefully monitor renal
      function and consider alternative dosing schedules and drug administration
      routes.

PMID- 11958390
TI  - Therapeutic thrombin injection of pseudoaneurysms: a multicenter experience.
AB  - The standard non-invasive treatment of pseudoaneurysms has been ultrasound-guided
      compression (UGC). Problems with UGC include pain at the site of compression,
      long compression times and incomplete closure. Each of these difficulties is
      exacerbated with large pseudoaneurysms. Recently, ultrasound-guided injection of
      pseudoaneurysms with thrombin has gained popularity. The goal of this study was
      to report a multicenter registry using this technique and in so doing detail the
      clinical utility and safety of this emerging procedure. The medical records of
      all patients diagnosed with pseudoaneurysm in the vascular laboratory who
      underwent thrombin injection over the past year were reviewed for patient
      characteristics and clinical outcome. There were 91 patients (55 male) with a
      mean age of 69 years. Three patients also had an arteriovenous fistula. The
      majority of patients were receiving one or more antiplatelet agents and/or
      anticoagulants. All patients underwent pseudoaneurysm injection with bovine
      thrombin. The mean aneurysm diameter was 3.3 cm, with a range of 1.5-6.3 cm.
      Successful thrombosis of the pseudoaneurysm was achieved in 89/91 (98%) of cases.
      Anticoagulation with heparin was used in one of the unsuccessful cases. In two
      cases, UGC was used to close a small active region that did not completely
      thrombose after thrombin injection. There were two patients who had recurrence of
      pseudoaneurysm the day after successful injection and thrombosis of the
      pseudoaneurysm. There were no local complications after injection; however, one
      patient suffered a pulmonary embolus that was thought to be unrelated to the
      procedure. In conclusion, thrombin injection for the treatment of pseudoaneurysms
      is safe and effective, even in patients receiving anticoagulation. This procedure
      should be considered as the initial therapeutic approach for peripheral
      pseudoaneurysms.

PMID- 11958391
TI  - Three cases of digital ischemia successfully treated with cilostazol.
AB  - Three patients were evaluated for refractory digital ischemia. The first patient
      presented with chronic, post-traumatic, unremitting, cold, painful, right fourth
      and fifth fingers. The symptoms had failed to improve despite topical
      nitroglycerin and a calcium channel blocker. Baseline digital plethysmography
      documented impaired perfusion within the affected digits. Cilostazol (Pletal) was
      added to the medical regimen and at the 8-week follow-up the fourth and fifth
      fingers were warm with repeat plethysmography displaying normal perfusion. A
      second patient had CREST syndrome-associated painful bilateral index finger
      ulcerations that had evolved despite taking a calcium channel blocker.
      Consequently the patient was started on cilostazol and within 4 weeks the digital
      ulcerations and pain had resolved. The third patient with traumatic right fifth
      digital arterial thrombosis was seen for persistent pain and cyanosis in spite of
      undergoing thrombolysis and subsequent anticoagulation with vasodilator therapy.
      Digital plethysmography established fixed ischemia within the fifth finger;
      subsequently, cilostazol was prescribed. Four weeks later the digital pain and
      cyanosis had essentially resolved. A follow-up plethysmographic waveform
      documented restored perfusion. Although approved for the treatment of
      intermittent claudication, cilostazol was successfully utilized in the setting of
      severe digital ischemia.

PMID- 11958392
TI  - Vascular complications in diabetes and their prevention.
AB  - Diabetes mellitus is increasing throughout the world. Cardiovascular disease
      (CVD) accounts for up to 80% of excess mortality in this high-risk population.
      Patients with diabetes have the same CVD risk factors as those people without
      diabetes. However, these risk factors are much more powerful in diabetic
      patients. CVD risk is especially high for diabetic women, and premenopausal
      diabetic women lose all the protection normally afforded to them by female sex
      hormones. Controlled clinical trials have clearly demonstrated that rigorous
      treatment of blood pressure, dyslipidemia and platelet hyperaggrebility
      strikingly reduces CVD risk in diabetic patients. Strategies directed at
      interrupting the renin-angiotensin system (both tissue and systemic systems) and
      the use of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors
      have proven to be especially beneficial for this high-risk population.

PMID- 11958393
TI  - Non-diabetic microalbuminuria, endothelial dysfunction and cardiovascular
      disease.
AB  - Subclinical increases in albuminuria (microalbuminuria) predict morbid events,
      but the reasons for that are still not understood in full. This paper reviews the
      existing evidence regarding the relationships of non-diabetic microalbuminuria
      and cardiovascular disease, the underlying assumption being that endothelial
      dysfunction contributes both to atherosclerotic macrovascular disease and renal
      microvascular disease of which albuminuria is a marker. Much data support that
      concept, and suggest a preferential link with endothelial activation in response
      to acute and subclinical inflammatory stimulation, although further studies are
      needed to establish the exact cause-effect mechanisms. Epidemiological studies
      also show associations with cardiovascular events, and some recent prospective
      results also indicate the power of microalbuminuria to predict risk independently
      from conventional atherogenic factors. Thus, microalbuminuria might be considered
      as an integrated marker of cardiovascular risk sensitive to systemic vascular
      status in addition to other parameters such as blood pressure levels, glucose
      metabolism, smoking habits, a profile rather unique among the prognostic
      predictors available to stratify risk in hypertensive patients.

PMID- 11958394
TI  - Images in vascular medicine. Popliteal artery entrapment syndrome.

PMID- 11958395
TI  - Images in vascular medicine. Stewart-Treves angiosarcoma.

PMID- 11958396
TI  - Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode
      of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12
      weeks of therapy after isolated calf deep vein thrombosis. Pinede L, Ninet J,
      Duhaut P et al for the Investigators of the 'Duree Optimale du Traitement
      Antivitamines K' (DOTAVK) study. Circulation 2001; 103: 2453-60.
AB  - QUESTION: Is anticoagulant treatment for calf vein thrombosis for 6 weeks
      duration associated with acceptable recurrence and safety outcomes? Is
      anticoagulant therapy for 3 months duration for proximal deep vein thrombosis
      (DVT) or pulmonary embolism (PE) associated with acceptable recurrence and safety
      outcomes? POPULATION: Men and women with a first episode of symptomatic calf vein
      thrombosis or proximal DVT confirmed by ultrasound or venography, or PE confirmed
      by lung scan or angiography. Patients with pregnancy, thrombophilia, severe PE,
      and cancer were excluded. DESIGN AND METHODS: After treatment with heparin and
      oral anticoagulants targeting an INR of 2-3, patients with calf DVT were
      randomized to 6 weeks (n = 105) versus 3 months (n = 92) of treatment, and
      patients with proximal DVT and/or PE were randomized to 3 months (n = 270) versus
      6 months (n = 269) of treatment. The outcome events were recurrences and major,
      minor, or fatal bleeding complications. The mean follow-up time was 12 months.
      RESULTS: A total of 736 patients were enrolled. For calf vein thrombosis the
      recurrence of DVT or PE after 6 weeks of therapy was 2/105 (2.0%) versus 3/92
      (3.4%) with 3 months of therapy, relative risk of 0.58 (95% CI: 0.10-3.36). The
      rates of major bleeding were 1/105 (1.0%) and 3/92 (3.4%) respectively, relative
      risk of 0.29 (95% CI: 0.03-2.72). For proximal DVT or PE, the recurrence rate
      after 3 months of therapy was 21/270 (8.1%) versus 23/269 (8.7%) after 6 months
      of treatment, relative risk of 0.93 (95% CI: 0.53-1.65). The rates of major
      bleeding were 5/270 (1.9%) versus 7/269 (2.6%) respectively, relative risk of
      0.73 (95% CI: 0.24-2.27). CONCLUSION: After isolated calf vein DVT, 6 weeks of
      oral anticoagulation is sufficient. For proximal DVT or PE, 3 and 6 months of
      anticoagulant therapy is equivalent. For patients with temporary risk factors who
      have a low risk of recurrence, 3 months of treatment seems to be sufficient.

PMID- 11958397
TI  - Time to think small.

PMID- 11958398
TI  - Evaluation of a tissue-engineered membrane-cell construct for guided bone
      regeneration.
AB  - PURPOSE: Currently, a number of bioresorbable and biodegradable membranes used
      for guided bone regeneration lead to incomplete tissue regeneration. Poor
      mechanical properties, short degradation time, and the lack of integrated
      biologic components result in the inability to create and maintain an appropriate
      environment and to actively support tissue remodeling. In the present study, the
      osteogenic potential of human calvarial periosteal cells in combination with
      ultrathin polycaprolactone (pc2) membranes of a slow biodegradation rate was
      investigated. MATERIALS AND METHODS: In vitro and in vivo analyses of the tissue
      engineered constructs were conducted using imaging techniques,
      immunohistochemistry, and histology. Two types of membranes were investigated.
      Group 1 consisted of a plain membrane, and in group 2 membranes were treated with
      sodium hydroxide. RESULTS: In vitro results showed that osteoblast-like cells
      attached and proliferated on the membranes with the formation of extracellular
      matrix. Sodium hydroxide-treated membranes showed enhanced cell attachment and
      proliferation kinetics, resulting in a dense cellular layer after 2 weeks in
      culture. In vivo mineralized tissue formation in association with vascularization
      was observed. Extracellular matrix calcification with nodule formation was
      detected via histology as well as scanning electron microscopy. DISCUSSION: PCL
      membranes support the attachment, growth, and osteogenic differentiation of human
      primary osteoblast-like cells. Sodium hydroxide-treated membranes demonstrated
      increased cell attachment resulting from increased hydrophilicity. CONCLUSION:
      These findings have potential application in the development of a new generation
      of osteoconductive membranes.

PMID- 11958399
TI  - The effect of 3 torque delivery systems on gold screw preload at the gold
      cylinder-abutment screw joint.
AB  - PURPOSE: This study measured the gold screw preload at the gold cylinder-abutment
      screw joint interface obtained by 3 torque delivery systems. MATERIALS AND
      METHODS: Using a precalibrated, strain-gauged standard abutment as the load cell,
      3 torque delivery systems tested were shown to have significant differences in
      gold screw preload when a gold cylinder was attached. RESULTS: Mean preloads
      measured were 291.2 N for hand torque drivers set at 10 Ncm, 340.3 N for
      electronic torque controllers at low setting/10 Ncm, 384.4 N for electronic
      torque controllers at high setting/10 Ncm; and 140.8 N for hand-tightening with a
      prosthetic slot screwdriver. Significant differences in screw preload were also
      found between operators using a hand torque driver. DISCUSSION: Hand-tightening
      delivered insufficient preload and cannot be recommended for final gold screw
      tightening. Different electronic torque controller units set at 10 Ncm induced
      mean gold screw preloads that ranged from 264.1 N to as high as 501.2 N.
      CONCLUSION: Electronic torque controllers should be regularly recalibrated to
      ensure optimal output.

PMID- 11958400
TI  - Growth factor levels in the platelet-rich plasma produced by 2 different methods:
      curasan-type PRP kit versus PCCS PRP system.
AB  - PURPOSE: Potential treatments using autologous thrombocyte growth factors are an
      important reason to improve methods for isolating platelet-rich plasma (PRP). Two
      methods for extracting PRP directly by the surgeon are currently available; this
      study was conducted to compare the growth factor levels in the resulting PRP.
      MATERIALS AND METHODS: Whole blood was drawn from 46 healthy donors (17 men, 29
      women) aged 20 to 59 years (29.9 +/- 7.8). PRP was then separated from each
      sample by both the PCCS (3i) and Curasan (PRP Kit, Curasan) methods. RESULTS: The
      growth factor content differed significantly for TGF-beta1 (PCCS 467.1 ng/mL;
      Curasan 79.7 ng/mL) (sign test P < .0001) and PDGF-AB (PCCS 251.8 ng/mL; Curasan
      314.1 ng/mL) (P < .0001); this was less significant for IGF-I (PCCS 91.0 ng//mL;
      Curasan 69.5 ng/mL) (P < .02). The higher platelet count in the PCCS PRP (PCCS
      2,232,500/microL; Curasan 1,140,500/microL) seemed to correlate with a higher
      level of TGF-beta1 (Spearman's correlation coefficient, r(s) = 0.7), whereas the
      higher leukocyte count in the Curasan PRP (PCCS 15,300/microL; Curasan 33,150/pL)
      had only a minor correlation with higher levels of PDGF-AB (r(s) = 0.46).
      DISCUSSION: The PCCS end product has both a higher platelet count and a higher
      total content of the growth factors investigated. Nevertheless, the biologic
      effect of the evaluated growth factor levels remains unknown. The amount of PRP
      necessary to achieve the intended biologic effects still remains unclear.
      CONCLUSION: PRP contains growth factors in high concentrations. Precise
      predictions of growth factor levels based on the thrombocyte counts of whole
      blood or PRP appeared limited. There are different sources for growth factors
      (platelets, leukocytes, plasma).

PMID- 11958401
TI  - Patient selection for endosseous dental implants: oral and systemic
      considerations.
AB  - This paper reviews the literature and discusses patient selection for endosseous
      dental implants and the effect of systemic and local pathology on the success
      rate of dental implants. Endosseous dental implants may be preferable to
      conventional dentures in patients with compromised supporting bone or mucosa,
      xerostomia, allergy to denture materials, severe gag reflex, susceptibility to
      candidiasis, diseases affecting orofacial motor function or in patients who
      demand optimal bite force, esthetics, and phonetics. Conventional dentures or
      fixed partial prostheses may be preferable to endosseous dental implants in
      growing and epileptic patients and patients at risk of oral carcinoma,
      anaphylaxis, severe hemorrhage, steroid crisis, endocarditis, osteoradionecrosis,
      myocardial infarction, or peri-implantitis. A systematic approach to dental
      implant patient selection is outlined and centralized reporting of dental implant
      outcomes is recommended.

PMID- 11958402
TI  - Effect of Nd:YAG, Ho:YAG, Er:YAG, CO2, and GaAIAs laser irradiation on surface
      properties of endosseous dental implants.
AB  - PURPOSE: To analyze potential surface alterations in endosseous dental implants
      induced by irradiation with common dental lasers. MATERIALS AND METHODS:
      Sandblasted and acid-etched, plasma-sprayed, hydroxyapatite-coated, and smooth
      titanium discs were irradiated using Nd:YAG, Ho:YAG, Er:YAG, CO2, and GaAIAs
      lasers at various power settings. The specimens were examined by scanning
      electron microscopy and energy dispersive spectroscopy. RESULTS: In an energy
      dependent manner, the pulsed YAG lasers induced partial melting, cracking, and
      crater formation on all 4 surfaces. Within the energy range applied, the CO2
      laser caused surface alterations on the hydroxyapatite and plasma coatings as
      well as in the acid-etched surface. GaAIAs laser irradiation did not damage any
      of the surfaces. Energy dispersive spectroscopy revealed an altered chemical
      compound of the surfaces with regard to titanium, oxygen, and silicon.
      DISCUSSION: The clinical application of most common dental laser systems can
      induce implant surface alterations. Relevant factors are not only the laser
      system and power setting, but also the application system. CONCLUSION: The
      results of the study indicate that Nd:YAG and Ho:YAG lasers are not suitable for
      use in decontamination of implant surfaces, irrespective of the power output.
      With the Er:YAG and CO2 laser, the power output must be limited so as to avoid
      surface damage. The GaAIAs laser seems to be safe as far as possible surface
      alterations are concerned.

PMID- 11958404
TI  - Accuracy of mechanical torque-limiting devices for implants.
AB  - PURPOSE: To examine the accuracy of 3 mechanical torque wrenches. MATERIALS AND
      METHODS: The torque outputs of the Nobel Biocare, Straumann ITI, and DynaTorq ITL
      mechanical torque-limiting devices were determined using a special setup on an
      Instron test machine. The devices were held in the test setup and oriented so
      that activation of the drivers caused a pure torsion effect. RESULTS: Significant
      differences generally existed between individual units and the target torque
      levels for the Nobel Biocare torque controller. DISCUSSION: The mean torque
      values of the ITI and ITL devices were within 10% of their respective target
      torque levels. Knowledge of applied torque levels to the screws that retain
      implant abutments and their attached prostheses is necessary to achieve optimal
      preload. The ITI and ITL devices tested in this study were capable of providing
      consistent torque at or near their respective targets. CONCLUSION: The torque
      output of each individual device deviated in varying degrees from target torque
      values.

PMID- 11958403
TI  - Fixed partial dentures supported by natural teeth and Branemark system implants:
      a 3-year report.
AB  - PURPOSE: To evaluate fixed partial dentures (FPDs) supported by a combination of
      natural teeth and implants in a variety of clinical situations. MATERIALS AND
      METHODS: In 30 patients, 86 teeth and 85 implants were used as supports for 30
      FPDs of varying extension (mean = 8.6 units); 23 in the maxilla and 7 in the
      mandible. The prostheses had a removable section fastened with screws to both the
      implants and to a section cemented on the supporting teeth, and were thus
      functioning as rigid, fixed partial dentures. RESULTS: Five implants were lost
      prior to the placement of prostheses, 2 were lost after loading, giving survival
      rates of 91.0% in the maxilla and 95.5% in the mandible. Complications were
      predominantly soft tissue-related and were all amenable to treatments. One
      patient was lost to follow-up. The remaining 29 FPDs remained stable throughout
      the 3-year observation period. DISCUSSION: Changes in plaque accumulated,
      bleeding on probing, pocket depths, and marginal bone level were acceptable. The
      survival rate of implants was comparable to that of similar studies. Further
      investigations are needed with regard to design for such FPDs. CONCLUSION: These
      findings, together with the patient satisfaction experienced, indicated that the
      combined support of implants and teeth for fixed prostheses may be appropriate
      treatment for patients.

PMID- 11958405
TI  - Longitudinal follow-up of osseointegrated implants in patients with resected
      jaws.
AB  - PURPOSE: To investigate the effects of bone grafting and radiotherapy on implant
      survival rates. MATERIALS AND METHODS: This follow-up study involved 36 patients
      with 180 implants who were treated between January 1989 and December 2000 by
      prosthodontic rehabilitation using osseointegrated implants following jaw
      resection. They comprised 20 patients with malignant tumors, 12 with benign
      tumors, and 2 patients each with osteomyelitis and cysts. RESULTS: A total of 15
      implants (11 in the maxilla and 4 in the mandible) were removed for various
      reasons during the follow-up study. Implant survival rates were calculated using
      the Kaplan-Meier method; the overall survival rate for the 180 implants was
      88.6%. Specific implant survival rates were as follows: in residual bone, 73.8%
      for the maxilla and 95.2% for the mandible; in grafted bone, 80% for the maxilla
      and 94.1% for the mandible; in irradiated bone, 79.7%; and in nonirradiated bone,
      93.5%. DISCUSSION: Radiotherapy, a dose of 30 Gy, was performed in patients with
      malignant tumors but not in patients with benign tumors, cysts, or osteomyelitis.
      No differences were found in the results for implants placed due to jaw resection
      for malignant tumors and those for implants placed due to benign tumors, cysts,
      or osteomyelitis. Implants lost varied in length from 7 to 18 mm. Among these,
      loss was more frequent with shorter implants (lengths to 10 mm). CONCLUSION: The
      clinical results obtained in the present study compare favorably with those
      obtained by others. However, jaw reconstruction and rehabilitation should not be
      performed by the oral surgeon alone; oral and maxillofacial function should be
      restored using a team approach in close cooperation with specialists in
      prosthodontics and periodontics to improve the result of implant treatment.

PMID- 11958406
TI  - Effects of prosthesis materials and prosthesis splinting on peri-implant bone
      stress around implants in poor-quality bone: a numeric analysis.
AB  - PURPOSE: A 3-dimensional finite element model consisting of a bone block and 2
      simulated premolar crowns supported by 2 adjacent cylindric implants without
      immediately surrounding cortical bone was generated and used to investigate the
      effects of prosthesis materials and prosthesis splinting on the peri-implant bone
      stress under static loads. MATERIALS AND METHODS: The peri-implant maximum
      equivalent bone stress (von Mises [VM] stress) was evaluated when a vertical or a
      horizontal load of 1 N was applied to the center of a single resin, gold alloy,
      or porcelain crown, nonsplinted or splinted to the adjacent crown. RESULTS: The
      numeric results indicated that: (1) in a single crown, no significant difference
      could be found in the maximum VM stress between different materials for both
      vertical and horizontal loading; (2) splinting the crowns reduced the maximum VM
      stress induced by the horizontal load, and the maximum VM stress increased about
      14% for the horizontal loading when the restorative material was changed from
      gold alloy or porcelain to resin. DISCUSSION: Under the condition of this study's
      analysis, prosthesis materials of a single crown have insignificant effects on
      the peri-implant bone stress. Splinting the crowns reduced the peri-implant bone
      stress under horizontal load, and gold alloy and porcelain each demonstrated less
      peri-implant bone stress than resin in the splinted crown situation under static
      horizontal load. CONCLUSION: Splinting the crowns of adjacent implants with
      relatively stiff restorative materials is recommended for implants surrounded by
      poor-quality bone.

PMID- 11958407
TI  - The use of ramus autogenous block grafts for vertical alveolar ridge augmentation
      and implant placement: a pilot study.
AB  - PURPOSE: This study presents a clinical, radiographic, laboratory, and
      histologic/histomorphometric analysis of the use of mandibular ramus block
      autografts for vertical alveolar ridge augmentation and implant placement.
      MATERIALS AND METHODS: Autogenous block autografts were fixed at the recipient
      site with fixation screws while a mixture of autogenous bone marrow and inorganic
      bovine material (Bio-Oss) was used at the periphery. All grafts appeared well
      incorporated at the recipient site during reentry surgery. RESULTS: Radiographic
      measurements revealed an average of 6.12 mm vertical ridge augmentation 1 month
      after surgery and 5.12 mm 4 to 6 months after surgery. Laboratory volumetric
      measurements revealed an average of 0.91 mL alveolar ridge augmentation 1 month
      after surgery and 0.75 mL 6 months postoperatively. Linear laboratory
      measurements revealed 6.12 mm of vertical ridge augmentation 1 month
      postoperatively and 4.37 mm 4 to 6 months after surgery. Histologic evaluation
      indicated signs of active remodeling in all the specimens. Histomorphometric
      analysis of the peripheral particulate bone indicated bone present at 34.33% of
      the grafted area, while 42.17% of the area was occupied by fibrous tissue and
      23.50% by residual Bio-Oss particles. DISCUSSION: The results demonstrated the
      potential of mandibular block autografts harvested from the ascending ramus to
      maintain their vitality. Volumetric resorption rate of 17.58% and radiographic
      resorption rate of 16.34% were in accordance with previously published
      literature. Early exposure appeared to compromise the results, while late
      exposures did not affect the vitality of the block autografts. CONCLUSION:
      Mandibular block autografts can maintain their vitality when used for vertical
      alveolar ridge augmentation. Inorganic bovine mineral (Bio-Oss) can be used at
      the periphery of the block graft when mixed with autogenous bone marrow.

PMID- 11958408
TI  - Dental implants placed in extraction sites implanted with bioactive glass: human
      histology and clinical outcome.
AB  - PURPOSE: To evaluate the clinical outcome of implants placed into sites grafted
      with bioactive glass. MATERIALS AND METHODS: Seventeen consecutively treated
      patients were referred to a private specialist surgical practice for the repair
      of dentoalveolar defects, and/or ridge maintenance at the site of extraction
      sockets, prior to implantation. Bioactive glass available in 1 of 2 forms was
      utilized as an alloplastic grafting material. Bone cores were trephined out at
      the time of implantation and processed and examined to evaluate the tissue
      response under the light microscope. Implant mobility, marginal bone levels, and
      soft tissue health were all evaluated over a 2- to 3-year follow-up period to
      determine treatment success. RESULTS: A total of 40 Astra Tech dental implants
      were placed. The overall success rate at the end of the study was 88.6% for
      implants that were in function for a mean period of 29.2 months (22 to 24
      months). One patient with 5 successful implants died at 18 months after
      functional loading. At that time the cumulative success rate was 90%. Another
      patient who was diagnosed with cancer of the large bowel lost 3 implants. If this
      patient were excluded from the data, the cumulative success rate increases to
      96.8%. Mean marginal bone loss measured 0.5 mm mesially and 0.4 mm distally over
      a maximum follow-up of 36 months. Human histology demonstrated that connective
      tissue was seen to exist without any inflammatory response, for up to 6 months.
      Increasing evidence of bone formation was seen in direct relation to the
      bioactive glass material beyond this time frame. DISCUSSION: The need to repair
      and augment dentoalveolar defects necessitates the use of autogenous bone or a
      substitute that may be seen to avoid the additional morbidity of a donor site
      procedure and without risk of cross infection. The use of bioactive glass has
      been proposed as a viable bone substitute. The current study draws attention to
      the long healing time required to achieve even a small amount of new bone
      incorporation into the graft, as seen histologically. However, the high rate of
      osseointegration and continued medium-term function of implants placed into these
      grafted sites would indicate that the use of bioactive glass does not prohibit
      osseointegration. However, it is likely that the initial integration will have
      derived from those areas in contact with native bone. CONCLUSION: Implants will
      survive for up to 3 years in sites grafted with bioactive glass, even when such
      grafts appear to only slowly conduct new bone growth.

PMID- 11958409
TI  - Risk management aspects of implant dentistry.
AB  - PURPOSE: To categorize and review complications related to implant dentistry that
      have resulted in legal actions. MATERIALS AND METHODS: The records of 61 patients
      (39 women and 22 men) were retrospectively evaluated according to a structured
      form. Ages ranged from 28 years to 78 years (mean 49 +/- 12 years). The time lag
      in months between actual damage and legal action ranged from 0 months to 60
      months (mean 12.7 months). RESULTS: Implant type, length, width, and locations
      varied widely and had no impact on the liability report. Half of the lawsuits
      were filed as a result of actual body damage (loss of sensation, oroantral
      fistula, life-threatening bleeding); 35% of the lawsuits were filed because of
      late complications; and 15% were related to immediate complications not leading
      to actual body damage. The dental consultants acknowledged liability in 41 of 61
      cases. The clinician's errors that led to the reported complication were
      classified as preoperative in 39 of 41 cases. The doctor's attitude was
      considered positive in 40 cases and negative in 17 cases. DISCUSSION AND
      CONCLUSIONS: Clinicians should report as soon as possible to their insurance
      companies to get professional help. The main causes for lawsuits are actual body
      injury and major disappointment. Practitioners should dedicate a significant part
      of the entire treatment time to preoperative diagnosis and planning.

PMID- 11958410
TI  - Assessment of accuracy of navigated implant placement in the maxilla.
AB  - PURPOSE: The use of computed tomography (CT) based intraoperative navigation has
      greatly improved surgery in many specialties. In this study, the precision of the
      SMN system (Zeiss, Oberkochen, Germany) for navigated drilling and following
      implant placement in the maxilla was evaluated. This study should demonstrate the
      suitability of navigation systems for computer-assisted implantation in the
      maxilla to avoid perforation of the maxillary sinus. MATERIALS AND METHODS: Sixty
      target drillings were carried out on 10 standardized polyurethane milling models
      after CT scanning. The models were produced with cranial open maxillary sinuses.
      The CT scans were performed with a slice distance of 1 mm. Then the CT data were
      transferred to the workstation of the SMN system and registration of the
      reference markers (fiducials) for superposition of the native and CT model was
      done. Referencing of the model was performed with the aid of a drilling tool.
      This drilling tool was used for later navigation-assisted drilling into the
      maxilla. The target of drilling was the maxillary sinus floor. The aim was to
      come as near as possible without perforation. The distance from the bottom of the
      drilling holes to the maxillary sinus floor was measured after sectioning of the
      model. In another 10 models, implants were placed after performing 60 navigated
      drilling holes. RESULTS: In the first part of the study, an average drilling
      depth of 6.97 mm and a mean distance to the sinus floor of 0.11 mm (standard
      deviation = 0.2) was found. In 13 specimens, the inferior border of the sinus was
      perforated. In the second part of the study, a perforation of the sinus floor by
      the implants was seen in 47 cases. The mean distance to the maxillary sinus was
      0.25 mm (standard deviation = 0.2). DISCUSSION AND CONCLUSIONS: High precision of
      CT-based navigation for controlled preimplant drilling was seen, but a high
      incidence of penetrations into the maxillary sinus was caused by the subsequent
      implant placement.

PMID- 11958411
TI  - Flapless implant surgery: a 10-year clinical retrospective analysis.
AB  - PURPOSE: This article is a retrospective clinical analysis of implants placed
      with a flapless approach. MATERIALS AND METHODS: Seven hundred seventy implants
      were placed in 359 patients to restore both completely edentulous and partially
      edentulous arches with fixed prostheses or removable complete dentures. Each
      patient was examined after 3 months, 6 months, 1 year, and then once every year.
      Prostheses were removed, if possible, and implant mobility was assessed,
      periapical radiographs were obtained, and periodontal probing was performed.
      Implants were considered failed if they had mobility or pain, had to be removed,
      or if they showed more than 0.5 mm of bone loss per year and signs of active peri
      implantitis. RESULTS: The cumulative success rate for implants placed using a
      flapless 1-stage surgical technique after a 10-year period varied from 74.1% for
      implants placed in 1990 to 100% at 2000. DISCUSSION: Since flapless implant
      placement is a generally "blind" surgical technique, care must be taken when
      placing implants. Angulation of the implants affected by drilling is critical to
      avoid perforation of the cortical plates, both lingual or buccal, especially on
      the lingual in the mandibular molar area and the anterior maxilla. There should
      be no problem if the patient has been appropriately selected and an appropriate
      width of bone is available for implant placement. There is a learning curve to
      every surgical procedure, after which it becomes routine. There are many
      advantages for the patient as well as for the surgeon, since the procedure is
      less time consuming, bleeding is minimal, implant placement is expedited, and
      there is no need to place and remove sutures. CONCLUSION: Flapless implant
      surgery is a predictable procedure if patient selection and surgical technique
      are appropriate.

PMID- 11958412
TI  - Treatment of congenital ectodermal dysplasia with zygomatic implants: a case
      report.
AB  - Dental abnormalities associated with ectodermal dysplasia (ED) can result in
      severe functional and esthetic problems. To correct these problems, dental
      implants have increasingly become the treatment of choice. This patient study
      illustrates the use of implants to rehabilitate a 20-year-old ED patient who
      initially presented with only 2 permanent and 6 primary teeth in the maxilla.
      Along with conventional endosseous implants, 2 specially designed zygomatic
      implants were utilized to avoid the need for bone grafting in the patient's
      severely resorbed maxilla. This expedited achievement of the final satisfactory
      result.

PMID- 11958414
TI  - Three-dimensional computed tomographic angiography with low loads of contrast
      agent in acute subarachnoid hemorrhage.
AB  - In the pre-operative evaluation of aneurysmal subarachnoid hemorrhage (SAH),
      three-dimensional computed tomographic angiography (3D-CTA) is very helpful.
      However, it is usually difficult to perform 3D-CTA following four-vessel cerebral
      angiography in the setting of acute SAH because of high loads of contrast agent.
      The present report is designed to enable 3D-CTA following catheter angiography
      for surgical planning. Fourteen consecutive patients with acute SAH underwent
      four-vessel cerebral angiography. After identification of the aneurysm, all
      patients were moved to the CT room next to the angiography room under
      catheterization. Contrast agent (10 ml) was diluted with 40 ml of heparinized
      saline. This diluted contrast agent was then injected through intra-arterial
      catheter for 3D-CTA. 3D-CTA with diluted contrast agent which was injected
      through intra-arterial catheter revealed sufficiently clear images. In addition,
      this method could provide anatomical information that was not readily available
      from catheter angiography. 3D-CTA with additional low dose of contrast agent can
      immediately follow four-vessel cerebral angiography in the setting of acute SAH.
      No complications were noted throughout the procedures. It has been our experience
      that the imaging modality in combination with not only catheter angiography but
      also 3D-CTA is advantageous in case of acute SAH and provides better detail for
      surgical planning.

PMID- 11958413
TI  - Protective effects of inhibiting both blood and vascular selectins after stroke
      and reperfusion.
AB  - Early intervention after acute ischemic stroke is essential to minimize brain
      cell injury. Although reperfusion of the ischemic brain is the treatment of
      choice for acute stroke, reperfusion itself may cause additional injury. The
      inflammatory cascade, characterized in part by early leukocyte interaction with
      endothelium, may contribute to this additional injury to blood vessels and
      surrounding brain tissue, extending the area of infarction. The selectin family
      of adhesion molecules mediates the initial, rolling and tethering of leukocytes
      to endothelium. P-selectin is rapidly expressed on ischemic endothelium in the
      brain vasculature, and L-selectin is expressed on leukocytes. Blocking the
      selectin-mediated tethering step may limit the inflammatory component of
      reperfusion injury in the brain. Fucoidin (FCN), a competitive inhibitor of P-
      and L-selectin, has been reported to decrease leukocyte accumulation during
      reperfusion of other organs. The effect of both leukocyte and endothelial
      selectin inhibition after cerebral ischemia and reperfusion has not been
      previously examined. The purpose of this study was to determine the effects of
      selectin adhesion molecule blockade on cerebral infarction size and neurological
      function after middle cerebral artery occlusion and reperfusion (MCAO-R) in the
      rat. MCAO was induced using the filament method. All animals were subjected to 4
      h of MCAO and 24 h of reperfusion. After 24 h, brains were analyzed for size of
      infarction. Neurological function was assessed during stroke and 24 h after
      reperfusion. Two groups were studied, an untreated control group (n = 9) and a
      group treated with the selectin inhibitor, fucoidin (25 mg kg(-1)) (n = 9). We
      found that selectin blockade significantly reduced cerebral infarction size by
      50% (p < 0.05) and improved neurological function (p < 0.05). In addition, a
      trend toward decreased cerebral edema was demonstrated with selectin inhibition.
      These results indicate that treatment of the blood and the endothelium with a
      selectin anti-inflammatory agent is protective after focal stroke and reperfusion
      in the rat.

PMID- 11958415
TI  - The anatomy of the circle of Willis as a predictive factor for intra-operative
      cerebral ischemia (shunt need) during carotid endarterectomy.
AB  - The collateral flow to the cerebral hemisphere after carotid cross clamping
      during carotid endarterectomy is mainly through the circle of Willis, and the
      circle is incomplete in the majority of cases. A correlation between the status
      of the circle of Willis and the necessity of shunting was evaluated in 67 carotid
      endarterectomies with pre-operative four-vessel cerebral angiogram. All carotid
      endarterectomies were performed with selective shunting, based on the change of
      consciousness and motor function after carotid test clamping under regional
      anesthesia. Of the 55 patients with either an anterior or a posterior
      communicating artery, only four (7.3%) required shunting. Twelve patients had
      neither anterior nor posterior communicating artery, and 10 (83.3%) showed signs
      of cerebral ischemia necessitating shunting. Mandatory shunt was significantly
      higher in patients with absence of collaterals (p = 0.00). The rate of
      intraoperative cerebral ischemia was significantly higher in patients with poor
      collateral circulation defined by the anatomy of the circle of Willis.

PMID- 11958417
TI  - Fibroblast growth factor receptor (FGFR) 4 correlated with the malignancy of
      human astrocytomas.
AB  - Fibroblast growth factor receptor (FGFR) 4 possesses high affinity to acidic and
      basic fibroblast growth factors (FGFs). The authors focused on FGFR 4 expression
      in astrocytoma because the FGF expression increases as the tumor malignancy
      progresses. Forty-one astrocytoma specimens were examined by immunohistochemistry
      and polymerase chain reaction-Southern blot. FGFR 4 was negative in all seven
      Grade II astrocytomas by immunohistochemistry, while positive in four among 15
      Grade III and in 13 among 19 Grade IV astrocytomas. The median survival time of
      Grade III astrocytoma patients was 22.3 months in FGFR 4 negative group and 14.5
      months in positive group (p < 0.05). Those of Grade IV patients were 14.2 months
      in FGFR 4 negative group and 11.9 months in positive group (p > 0.05, not
      significant). However, FGFR 4 mRNA was detected in all specimens suggesting
      activated translation system of FGFR 4 in progression of the tumor malignancy.
      Histologically diagnosed Grade III astrocytoma patients can be divided into two
      groups; one with median survival time close to those with Grade II astrocytoma
      patients, and the other similar to that of glioblastoma patients. The authors
      concluded that FGFR 4 must be an important factor which predicts short survival
      Grade III astrocytoma patients, who require strict adjuvant therapy in accordance
      with glioblastoma.

PMID- 11958416
TI  - Topoisomerase II alpha as a reliable proliferation marker in meningiomas.
AB  - The value of DNA Topoisomerase IIalpha expression as a proliferation marker in
      meningiomas was investigated. The correlation to MIB-1 expression and tumor grade
      in 85 meningiomas (60 classical, 19 atypical and 6 anaplastic) was analysed by
      immunohistochemistry. MIB-1 labeling indices (LI) were 1.1% (+/- 0.85) for
      classical meningiomas, 1.9% (+/- 1.5) for atypical meningiomas and 5.6% (+/- 4.1)
      for anaplastic meningiomas, differences statistically significant (p = 0.03, <
      0.0001, < 0.0001). Topoisomerase IIalpha LIs were 1.4% (+/- 1.2) for classical,
      3.2% (+/- 2.4) for atypical and 9.7% (+/- 6.6) for anaplastic meningiomas,
      differences statistically significant (p = 0.003, < 0.0001, < 0.0001).
      Proliferation indices based on cells staining for MIB-1 and Topoisomerase IIalpha
      correlated highly with one another (r= 0.906, p <0.0001). Topoisomerase IIalpha
      exhibited a more distinct, less variable nuclear staining pattern compared to MIB
      1 expression. DNA Topoisomerase IIalpha LI represents a reliable alternative to
      MIB-1 as a proliferation marker in human meningiomas, especially for computer
      assisted assessment, where a distinct uniform staining pattern is required.

PMID- 11958418
TI  - Shift from hypermetria to hypometria in multiple system atrophy: analysis of
      distal and proximal movements.
AB  - Dysmetria is a classical sign which designates the overshoot, also called
      hypermetria, and the undershoot, or hypometria, when the patient attempts to
      reach rapidly an aimed target. Dysmetria is typically observed in patients
      presenting a cerebellar dysfunction. Dysmetria of distal movements is associated
      with an imbalance between the timing and/or the intensity of agonist and
      antagonist EMG activities. So far, 1. there is only one description in human of a
      shift from hypermetria to hypometria for fast goal-directed single-joint
      movements during an aberrant recovery following a cerebellar infarction, and 2.
      such a shift has not been described for proximal movements. We report a patient
      presenting a multiple system atrophy (MSA). Initially, he exhibited a marked
      cerebellar syndrome. Fast wrist flexions and fast upper limb reaches in the
      sagittal plane were hypermetric. The distal hypermetria was associated with a
      delayed onset latency of the antagonist EMG activity and reduced intensities of
      both the agonist and the antagonist EMG activities. The proximal hypermetria was
      associated with a defect in the phasic spatial tuning of the EMG activities. He
      developed progressively severe extra-pyramidal signs. Distal hypermetria turned
      into hypometria, as a result of a decrease in the intensity of the agonist
      muscle. Proximal hypermetria turned into hypometria, as a result of the loss of
      directional preference of the EMG activities in proximal muscles. MSA is the
      second human model of a shift from hypermetria to hypometria.

PMID- 11958419
TI  - Minimally invasive endoscope-assisted endonasal trans-sphenoidal microsurgery for
      pituitary tumors: experience with 215 cases comparing with sublabial trans
      sphenoidal approach.
AB  - Recent advances in endoscopic surgery have developed an endonasal route suitable
      for pituitary surgery. The main goal of this article is to evaluate benefits of
      our endoscope-assisted endonasal trans-sphenoidal microsurgery for pituitary
      tumors in 215 consecutive cases. The pathological classifications of the 215
      cases are as follows: 163 pituitary adenomas, 23 Rathke's cleft cysts, 17
      craniopharyngiomas, and 12 others. The patients were surgically treated via the
      endonasal trans-sphenoidal approach using an operating microscope as the primary
      instrument for tumor resection. Endoscopes were used to complement the operating
      microscope in visualization. We compared the new approach to the sublabial trans
      sphenoidal approach (197 cases) with respect to endocrinological outcomes and
      surgical complications. Our endonasal trans-sphenoidal approach was beneficial in
      eliminating the complications of lip numbness, which was often observed in
      patients undergoing sublabial surgery, and nasal septal perforation. In addition,
      endocrinological outcome comparable to those in the sublabial group was achieved
      in the endonasal group. We consider that the endoscope, which allows
      visualization of areas not seen with the operating microscope, should be used
      actively in conjunction with the operating microscope that provides three
      dimensional visualization and is timesaving. Our surgical method for pituitary
      tumors provides good results with minimal invasion, by exploiting the advantages
      of a microscope and an endoscope.

PMID- 11958420
TI  - Spatial and temporal characteristics of visual motion perception involving V5
      visual cortex.
AB  - The anatomical substrates of the perception of motion have not yet been
      established in a detailed way on an individual level. The aim of this study was
      to develop a systematic procedure for mapping the visual cortex using
      Transcranial Magnetic Stimulation (TMS). The results showed that such an
      individual and detailed map of the spatial and temporal characteristics of motion
      perception can be constructed using TMS.

PMID- 11958421
TI  - Adequate cerebral perfusion pressure during rewarming to prevent ischemic
      deterioration after therapeutic hypothermia.
AB  - Ischemic deterioration during rewarming is one of the most notable clinical
      complications after successful therapeutic cerebral hypothermia, but the
      mechanism is not completely understood. Hypothermia may cause vasoconstriction
      and relative ischemia, especially with insufficient cerebral perfusion pressure
      (CPP). Various parameters were evaluated to determine the critical CPP threshold
      to avoid ischemia during rewarming. Cat experimental head injury was induced by
      inflating an epidural rubber balloon, and intracranial pressure was maintained at
      30 mmHg. During rewarming after cerebral hypothermia, CPP was maintained at >120
      mmHg (n = 16), 90 mmHg (n = 11), 60 mmHg (n = 11), and 40 mmHg (n=4) by
      controlling the blood pressure. Cerebral blood flow, cerebral metabolic rate for
      oxygen, arteriovenous difference of oxygen (AVDO2), cerebral venous oxygen
      saturation (ScvO2), and extracellular glutamate concentrations were monitored by
      glutamate oxidase electrode. After rewarming, the cerebral metabolic parameters
      were almost restored to the pre-injury level in animals with CPP of more than
      90mmHg. However, in the animals with CPP= 60 mmHg, all parameters significantly
      deteriorated and indicated misery perfusion; ScvO2 was low (29.5+/-1.1%), AVDO2
      was significantly high (9.9+/-0.8 ml 100 g(-1) min(-1)) (one-way analysis of
      variance, p<0.05), and electron microscopic features showed subcellular ischemic
      change. Extracellular glutamate significantly increased during the rewarming
      period only in the CPP= 40 mmHg group. CPP less than 60 mmHg during rewarming
      causes secondary ischemic insult, which might indicate continuation of cerebral
      vasoconstriction in hypothermia. CPP higher than 90 mmHg is required to avoid the
      potential risk of relative ischemia after hypothermia.

PMID- 11958422
TI  - Impaired intracellular signal transduction via cyclic AMP contributes to cerebral
      vasospasm in rats with subarachnoid hemorrhage.
AB  - No drug can completely prevent vasospasm after subarachnoid hemorrhage. Impaired
      intracellular signal transduction by cyclic nucleotides might be involved. We
      investigated effects of intravenous isoproterenol and NKH477 on cerebral blood
      flow in rats with or without intracisternal injection of autologous blood one
      week previously. In controls without hemorrhage, isoproterenol at 0.01, 0.1, 1,
      and 10 mg kg(-1) min(-1) increased cerebral blood flow by 1.2%+/-9.5%, 19.7%+/
      12.8%, 46.8%+/-23.5%, and 63.8%+/-32.9% respectively; 10mg kg(-1) min(-1) of
      isoproterenol increased systemic blood pressure by 66.6%+/-58.1%, while other
      doses decreased blood pressure. In the subarachnoid hemorrhage group,
      isoproterenol increased cerebral blood flow by -20.0%+/-6.5%, -7.6%+/-8.7%,
      8.2%+/-8.8%, and 35.9%+/-83.1% respectively; 10 mg kg(-1) min(-1) of
      isoproterenol increased systemic blood pressure by 68.8%+/-79.5%, while other
      doses decreased blood pressure. In controls, NKH477 at 3, 10, and 30 mg kg(-1)
      increased cerebral blood flow by 2.3%+/-3.6%, 14.4%+/-7.0%, and 50.7%+/-14.6%,
      respectively; in the subarachnoid hemorrhage group, NKH477 changed cerebral blood
      flow by -1.3%+/-2.4%, 4.6%+/-2.8%, and -12.6%+/-10.8% (not significant difference
      from controls). NKH477 at 30 mg kg(-1) min(-1) decreased systemic blood pressure
      in both groups, but the effect in the hemorrhage group was greater. Either
      isoproterenol or NKH477 at appropriate doses can increase cerebral blood flow in
      vasospasm following subarachnoid hemorrhage without decreasing blood pressure.

PMID- 11958423
TI  - The relationships among ultrastructural angiogenic features, Na+ K+, Ca+2, Mg+2
      ATP-ase activities and SOD concentration in the microvasculature of intracranial
      meningiomas and glial tumors.
AB  - The purpose of this study was to investigate the relationship among
      ultrastructural angiogenic features, adenosine-5'-triphosphatase (ATP-ase)
      activities and superoxide dismutase (SOD) concentration in the microvasculature
      of intracranial meningiomas and glial tumors. We examined 20 tumor materials from
      20 adult patients with intracranial meningioma or glial tumor who underwent
      selective surgery, dividing them into two groups based on the type of the tumors.
      Group I consisted of 10 meningioma-materials, and Group II of 10 glial tumor
      materials. Na+-K+, Mg+2 and Ca+2 ATP-ase activities in Group I were significantly
      higher than those in Group II (p < 0.01). The SOD activity in Group I was
      significantly lower than that in Group II (p < 0.01). According to electron
      microscopic findings, vascular endothelial proliferation and ultrastructural
      cytoplasmic changes in the glial tumors were more prominent than those in the
      meningiomas. Our results show that there is a meaningful correlation among an
      increased endothelial proliferation, a decreased ATP-ase level and an increased
      SOD activity in the meningiomas and glial tumors.

PMID- 11958424
TI  - ACoA angle measured by computed tomographic angiography and its relevance in the
      pterional approach for ACoA aneurysms.
AB  - The purpose of this study was to analyze the spatial disposition of the anterior
      communicating artery (ACoA) complex and the orientation of the ACoA plane by
      computed tomographic angiography with three-dimensional reconstruction (3D-CTA)
      and to evaluate the relevance of the orientation of the ACoA plane in the
      planification of the surgical approach to the ACoA complex aneurysms. The
      dominance of the right or left A1 segment of the anterior cerebral artery, the
      position of the A1-A2 junction in relation to the transverse plane and the
      angulation of plane of the ACoA traject were studied using 3D-CTA in 30 patients
      with subarachnoid hemorrhage. Twelve patients harbored an aneurysm on the ACoA
      complex and the most relevant anatomic characteristics of these lesions were
      recorded. In 56.7% of cases both A1 segments were similar in size, whereas in
      33.3% of cases the left A1 segment was dominant and in the remaining 10% the
      right A1 segment was dominant. The position of the left A1-A2 junction was
      anterior to the transverse plane in 30% of cases with an angulation of the ACoA
      plane of 42+/-6 degrees. All patients with this anatomical arrangement and left
      A1 dominance (seven cases) harbored an aneurysm of the ACoA complex located on
      the left A1-A2 junction. The right A1-A2 junction was anterior to the transverse
      plane in 13.3% of cases with an angulation of the ACoA plane of 37+/-9 degrees.
      All patients in this situation and right A1 dominance (three cases) had an
      aneurysm on the ACoA complex. Finally, in 50% of cases the ACoA plane was on the
      transverse plane. In this group of cases only two patients harbored an aneurysm
      located on the ACoA segment. The dominance of an A1 segment of the anterior
      cerebral artery may develop anatomical changes in the ACoA complex due to the
      hemodynamic stress. The main result is the advance of the A1-A2 junction point in
      the dominant side and the angulation of the ACoA plane in relation to the
      transverse plane as well as the development of aneurismatic lesions. The
      angulation of the ACoA plane, in combination with the orientation of the
      aneurysm, must be included among the criteria for the selection of the route of
      the surgical approach. This information is given by the 3D-CTA. All of these data
      allows a pre-operative simulation of the surgical approach to the lesion for a
      safer clipping of the neck of the aneurysm.

PMID- 11958425
TI  - Delayed effects of the microvascular decompression on hemifacial spasm: a
      retrospective study of 131 consecutive operated cases.
AB  - We reviewed 131 consecutive cases operated for hemifacial spasm (HFS) by the same
      surgeon between January 1983 and April 1999. Microvascular decompression (MVD)
      was performed via lateral suboccipital approach. Post-operative follow-up ranged
      from 1.5 to 10 years (average 34 months). The final outcome divided into three
      categories, excellent (total recovery) in 120 cases (91.6%), partial (> 75%
      recovery) in 4 cases (3.1%), and unchanged or recurrent in 7 cases (5.3%). Only 2
      cases were re-operated, and final outcome of both was excellent. Based on these
      data, we aimed to determine a period of the final judgement of MVD effect and the
      causative factors of delayed effects on HFS retrospectively. There were 102
      complete recovered cases without hemifacial paralysis; immediate recovery from
      HFS was observed in 78 cases (76.5%), after 1 month in nine cases, 1-3 months in
      5 cases, 3-6 months in 3 cases, 6-10 months in 2 cases, and 10-12 months in 5
      cases. Thus, most cases were completely recovered within one year of observation.
      On the other hand, there was no statistically significant difference between
      immediate and delayed relief cases in clinical histories or operative
      observations. Therefore, our results suggest that the final judgement of the MVD
      effect could be made at least one year after surgery.

PMID- 11958427
TI  - Experimental bacterial meningitis in rats: demonstration of hydrocephalus and
      meningeal enhancement by magnetic resonance imaging.
AB  - We investigated whether magnetic resonance imaging (MRI) is able to detect
      intracranial manifestations of advanced bacterial meningitis in rats. Meningitis
      was induced in nine animals by injecting 150 microl 10(7) colony forming units
      per ml of Streptococcus pneumoniae into the cisterna magna. MRI was performed 24
      h (n = 5) and 48 h (n = 4) after infection. Controls included (I) animals that
      were injected intracisternally with 150 microl phosphate-buffered saline or (II)
      animals without puncture of the cisterna magna. T2-weighted and T1-weighted MR
      images before and after administration of 0.3 mmol kg(-1) of gadolinium-DTPA were
      obtained. Hydrocephalus was found in 7 of 9 infected animals, but not in the
      control group. Abnormal leptomeningeal enhancement was found in all infected
      animals, but in none of the controls. The animals imaged after 48 h showed a more
      pronounced hydrocephalus and a more intense leptomeningeal enhancement than
      animals imaged after 24 h. Even in small animals such as rats, MRI can be used to
      detect the presence of bacterial meningitis and its associated complications. MRI
      may be a useful noninvasive method for monitoring the possible effect of
      adjunctive therapeutic strategies in experimental studies of meningitis.

PMID- 11958426
TI  - Nonenzymatic derived lipid peroxide, 8-iso-PGF2 alpha, participates in the
      pathogenesis of delayed cerebral vasospasm in a canine SAH model.
AB  - We studied whether 8-iso-PGF2alpha, nonenzymatic arachidonyl peroxide,
      participated in the pathogenesis of delayed vasospasm using a canine subarachnoid
      hemorrhage (SAH) model. Fourteen adult mongrel dogs were divided into two groups,
      two-hemorrhage SAH group (n = 8) and control group (n = 6). The contents of 8-iso
      PGF2alpha in CSF, the basilar artery segment, and subarachnoid clot were measured
      by enzyme immunoassay kit. The CSF 8-iso-PGF2alpha content on Day 7 in the SAH
      group was 67.9+/-29.9 pg ml(-1) (n = 8), which was significantly higher than
      27.1+/-13.8 (n = 8) on Day 0 in the SAH group, and 33.2+/-14.4 pg ml(-1) (n = 5)
      on Day 7 in the control group. The 8-iso-PGF2alpha content in the basilar artery
      segment with spasm on Day 7 in the SAH group was 13.5+/-1.9 pg mg(-1) wet weight
      (n = 8), significantly higher than 8.7+/-1.9 (n = 6) in the control group. The 8
      iso-PGF2alpha content in subarachnoid clot was 1.7+/-1.4 ng g(-1) wet weight (n =
      8). Significant elevation of the 8-iso-PGF2alpha contents in the CSF and the
      basilar artery segment occurred on Day 7 in the SAH group. The subarachnoid clot
      enclosed the basilar artery on Day 7, contained a considerable amount of 8-iso
      PGF2alpha. These results suggested that 8-iso-PGF2alpha could play a crucial role
      in the pathogenesis of the delayed cerebral vasospasm.

PMID- 11958428
TI  - Monteplase reduces infarct volume and hemorrhagic transformation in rat model of
      embolic stroke.
AB  - Monteplase, a modified recombinant tissue plasminogen activator (rt-PA), has a
      long half-life and reduces binding to plasminogen activator inhibitor. In this
      study we investigated whether its systemic administration reduces infarct volume
      without increasing the risk of intra-cerebral hemorrhage. The effect of the drug
      was tested on an embolic stroke rat model that uses white clots. Thirty minutes
      after clot embolization, rats were infused with 2.2 mg kg(-1) of monteplase or
      the same amount of saline, over 60 min. Relative regional cerebral blood flow had
      recovered 60 min after monteplase administration and infarct volume was
      significantly smaller 24 h after clot embolization in the monteplase-treated rats
      (47.0 mm3) than in the saline-treated rats (130.4 mm3). Also, the hemorrhagic
      transformation area was significantly smaller in monteplase-treated rats (0.8 mm2
      vs. 18.0 mm2, respectively). These results indicate monteplase can be a promising
      thrombolytic agent for treatment of the acute stage of cerebral ischemia.

PMID- 11958430
TI  - Enhanced expression of p53 in reactive astrocytes following transient focal
      ischemia.
AB  - The present study used immunohistochemistry to investigate p53 expression in rat
      brain following transient occlusion of the middle cerebral artery. In the control
      group, no p53-immunoreactive cells were found in any region of the central
      nervous system. P53 expression in reactive astrocytes was not obvious in the
      forebrain one day or three days following ischemic insults. Seven days following
      ischemic injury, increased expression of p53 was clearly detectable in reactive
      astrocytes in affected cortical regions, such as forelimb area, hindlimb area,
      and parietal cortex. At seven days of recirculation, there was also a significant
      increase in the number of p53-immunoreactive neurons in the cerebral cortex,
      striatum, and hippocampal CA1-3 regions. Although the present study has not
      addressed multiple mechanisms contributing to cell death following ischemic
      injury, the first demonstration of a significant increase in p53 expression in
      glial cells may prove useful for future investigations of the pathophysiology of
      ischemia.

PMID- 11958431
TI  - Cardiac findings of reactive arthritis: an observational echocardiographic study.
AB  - The aim of this study was to assess echocardiographically the occurrence of
      cardiac abnormalities in patients with acute reactive arthritis (ReA). Eighteen
      consecutive adult patients with acute ReA were studied by the use of two
      dimensionally guided M-mode and Doppler echocardiography. Aortic or mitral
      regurgitation were both detected in one of the patients. Mild to moderate left
      ventricular dilatation was observed in five patients, in four of whom the
      duration of acute ReA was over 6 months. In four patients, the ratio of peak
      early and peak late transmitral filling velocities was decreased. No patient had
      echocardiographic signs of myocarditis or pericardial effusion. In conclusion, no
      major structural cardiac alterations were detected. Mild valvular disease or mild
      to moderate left ventricular dilatation was observed in a quarter of the
      patients. Echocardiographic evaluation may be warranted if the acute ReA persists
      or has a prolonged course but is not recommended for routine use.

PMID- 11958429
TI  - Intracerebral adenosine infusion improves neurological outcome after transient
      focal ischemia in rats.
AB  - Second Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd.,
      Tokushima, Japan In order to elucidate the role of adenosine in brain ischemia,
      the possible protective effects of adenosine on ischemic brain injury were
      investigated in a rat model of brain ischemia both in vitro and in vivo.
      Exogenous adenosine dose-dependently rescued cortical neuronal cells from injury
      after glucose deprivation in vitro. Adenosine (1 mM) also significantly reduced
      hypoglycemia/hypoxia-induced glutamate release from the hippocampal slice. In a
      rat model of transient middle cerebral artery occlusion (MCAO), extracellular
      adenosine concentration was increased immediately after occlusion, and then
      returned to the baseline by 30 min after reperfusion. Adenosine infusion through
      a microdialysis probe into the ipsilateral striatum (1 mM adenosine, 2 microl
      min(-1), total 4.5 h from the occlusion to 3 h after reperfusion) showed a
      significant improvement in the neurological outcome, and about 25% reduction of
      infarct volume, although the effect did not reach statistical significance,
      compared with the vehicle-treated group at 20 h after 90 min of MCAO. These
      results demonstrated the neuroprotective effect of adenosine against ischemic
      brain injury both in vitro and in vivo, suggesting the possible therapeutic
      application of adenosine regulating agents, which inhibit adenosine uptake or
      metabolism to enhance or maintain extracellular endogenous adenosine levels, for
      stroke treatment.

PMID- 11958432
TI  - Lack of association of interleukin-1beta gene polymorphisms in Chinese patients
      with systemic lupus erythematosus.
AB  - The purpose of this study was to examine whether interleukin-1beta (IL-1beta)
      (promoter and exon 5) gene polymorphisms were markers of susceptibility or
      clinical manifestation in Chinese patients with systemic lupus erythematosus
      (SLE). The study included 52 Chinese patients with SLE. In addition, 103
      unrelated healthy individuals living in central Taiwan served as control
      subjects. From genomic DNA, polymorphisms of the gene for IL-1beta promoter and
      exon 5 were typed. Allelic frequencies were compared between SLE patients and
      control subjects. The relationship between allelic frequencies and clinical
      manifestations of SLE was evaluated. No significant differences were observed in
      the allelic frequencies of the IL-1beta promoter and IL-1beta exon 5 between
      patients with SLE and healthy control subjects. Additionally, we did not detect
      any association of IL-1beta promoter and the exon 5 genotype with the clinical
      and laboratory profiles in SLE patients. The results from the present study
      suggest that the polymorphisms of the IL-1beta promoter and IL-1beta exon 5 are
      not related to SLE patients in Taiwan.

PMID- 11958433
TI  - Clinical features of Behcet's disease in patients in the Sultanate of Oman; the
      significance of antiphospholipid antibodies?
AB  - The prevalence of symptoms in 34 Omani patients with Behcet's disease (BD) was:
      recurrent oral ulceration 100%, arthritis/arthralgia and genital ulceration 74%
      each, folliculitis 64%, neurological lesions 62%, retinal vasculitis 30%, iritis
      and hypopyon 26%, gastrointestinal lesions 12%, venous thrombosis and
      cardiovascular lesions 9% each, and pleuropulmonary lesions and epididymitis 6%
      each. Antiphospholipid (APL) antibodies (both anticardiolipin [ACAs] and anti
      beta2 glycoprotein I [abeta2GPIs]) were present in 11/34 (32%) of the BD patients
      and in 54/73 (74%) of Omani patients with systemic lupus erythematosus (SLE)
      (chi2 = 21.2, P<0.001). In patients possessing APL antibodies, there was no
      significant difference in mean antibody levels between BD and SLE patients. IgM
      isotype antibodies, in the absence of IgG, were more prevalent in BD (5/11) than
      in SLE (10/54) patients (chi2 =3.8, P = 0.05). The frequency of organ involvement
      was similar in patients with and without APL antibodies (chi2 = 1.226, P > 0.05).
      This study fails to demonstrate a pathognomonic role for APL antibodies in BD.

PMID- 11958434
TI  - CD69 expression on lymphocytes and interleukin-15 levels in synovial fluids from
      different inflammatory arthropathies.
AB  - OBJECTIVE: The aim was to study a possible relationship between CD69 expression
      on lymphocytes and interleukin-15 (IL-15) levels in synovial fluid (SF) from
      patients with different inflammatory arthropathies. METHODS: CD69 expression was
      assessed by two-color flow cytometry on different subsets of synovial fluid
      lymphocytes (SFL) obtained from patients with diagnoses of rheumatoid arthritis
      (RA), seronegative spondyloarthropathy (SSd), and crystal-associated arthritis
      (CAA). The IL-15 levels in synovial fluid supernatants were measured by enzyme
      linked immunoassay (ELISA). RESULTS: No significant differences between the three
      groups of arthropathies were observed in the distribution of synovial fluid
      lymphocyte subsets. CD69-positive SFL were mainly CD3-, CD45RO-, and CCR5
      positive cells. Although no significant differences in the percentage of CD69
      positive lymphocytes were observed between the three groups of patients, the
      highest level of CD69 expression on lymphocytes was observed in RA patients (mean
      fluorescence intensity 37.9 +/- 5.2 compared to 17.5 +/- 3.3 in SSd and 12.4 +/-
      2.6 in CAA, P = 0.007 and P < 0.001, respectively). In addition, the expression
      of CD69 on SFL from RA correlated with their respective IL-15 levels measured in
      SF supernatants. CONCLUSION: Our data provide in vivo evidence of the putative
      role that IL-15 can play in the high expression of CD69 on SFL from RA patients.

PMID- 11958435
TI  - The CD14+ CD16+ monocyte subset in rheumatoid arthritis and systemic lupus
      erythematosus.
AB  - Most human peripheral blood monocytes strongly express surface CD14, but not CD16
      (CD14+ +/CD 16-). A smaller group of monocytes express lower levels of CD14 and
      also express CD16 (CD14+/CD16+). This subgroup has different functional
      characteristics and is expanded in a number of disease states. We aimed to
      determine the percentage of circulating CD14+ /CD16+ monocytes in rheumatoid
      arthritis and systemic lupus erythematosus (SLE) and relate this to disease
      measures. Peripheral blood was sampled from 31 SLE patients, 19 rheumatoid
      arthritis patients, and 19 healthy controls. The percentage of CD14+/CD16+
      monocytes was determined by immunofluorescence labelling and dual colour flow
      cytometry. The percentage of CD14+/CD16+ monocytes was significantly lower in
      rheumatoid arthritis (median 4.90%) than in normal subjects (median 7.30%, P =
      0.014), and in rheumatoid arthritis than in SLE patients (median 9.40%, P =
      0.009). The percentage of CD14+/CD16+ monocytes in SLE was not significantly
      different from that in healthy subjects. This lower percentage of CD14+/CD16+
      monocytes in rheumatoid arthritis may be important in the pathogenesis of this
      disease.

PMID- 11958436
TI  - Correlation of bone and cartilage markers in the synovial fluid with the degree
      of osteoarthritis.
AB  - In recent years, many biochemical markers were tested with the aim of developing
      a tool for the early detection and monitoring of osteoarthritis (OA). Apart from
      chondral markers, we also evaluated osseous markers from the synovial fluid to
      obtain more comprehensive information, and we compared the levels in relation to
      the severity of OA. In this prospective, cross-sectional study, synovial fluid
      samples were obtained from 73 patients with OA of the knee joint prior to
      operation and after the joint was flushed with 50 ml of normal saline. All
      patients underwent surgery and were classified in accordance with the Outerbridge
      and the Noyes classification. The measured biochemical markers included
      pyridinoline (PD), deoxypyridinoline (DPD), N-telopeptide (NTx), carboxyterminal
      propeptide of collagen-1 (PICP), matrix metalloproteinases (MMP-1 and MMP-3), and
      tissue inhibitor of MMPs (TIMP-1). The marker levels were normalized against the
      total protein content and were compared with the Outerbridge and the Noyes
      classification. For the majority of markers, the correlation coefficient was
      below r=0.3, with large 95% confidence intervals. The highest correlation
      coefficients were obtained from DPD and TIMP-1. In relation to the Outerbridge
      classification, DPD revealed high values only in stage IV. The overall results
      indicate that the majority of the tested markers are unspecific with regard to
      the different stages of OA. The two markers with the highest correlation
      coefficients showed no major sensitivity to detect OA at an initial stage.
      However, they might give additional information to clinical and radiological
      findings with regard to the severity of the disease.

PMID- 11958437
TI  - Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in
      serum of patients with rheumatoid arthritis.
AB  - The aims of our study were to assess whether the increased oxidative stress in
      inflamed joints is reflected by serum lipid peroxidation and also to check
      alterations in the levels of extracellular antioxidants and antioxidant enzyme
      activities in patients with rheumatoid arthritis. Serum malondialdehyde and
      ceruloplasmin levels and the activity of CuZn superoxide dismutase were higher,
      while transferrin levels and the activities of glutathione peroxidase and
      catalase were lower in patients (n = 37) than in healthy controls (n = 30).
      Disease activity score correlated positively with serum malondialdehyde level and
      CuZn superoxide dismutase activity. Probably, superoxide radicals in serum could
      be dismutated to produce hydrogen peroxide by increased CuZn superoxide dismutase
      activity, but hydrogen peroxide could not have been detoxified due to decreased
      activities of serum glutathione peroxidase and catalase. Hydrogen peroxide
      possibly converted to hydroxyl radical by iron due to lower transferrin level
      might have led to increased serum lipid peroxidation in patients with rheumatoid
      arthritis.

PMID- 11958438
TI  - Ochronotic arthropathy.
AB  - Ochronotic arthropathy is the musculoskeletal manifestation of alkaptonuria. an
      uncommon inherited metabolic disorder associated with various clinical and
      radiologic abnormalities due to the deposition of homogentisic acid. We report on
      a 35-year-old man with ochronotic arthropathy who presented with the main
      characteristic radiological findings. The differential diagnosis of this rare
      condition is discussed with a review of the literature.

PMID- 11958439
TI  - Balneotherapy for fibromyalgia at the Dead Sea.

PMID- 11958440
TI  - The development and role of predictive instruments in acute coronary events:
      improving diagnosis and management.
AB  - The diagnosis and management of acute myocardial infarction and unstable angina
      pectoris are frequent challenges for emergency department staff. Strategies must
      quickly and accurately identify all patients requiring admission, monitoring, and
      reperfusion therapy to maximize outcomes without overdiagnosing. The Acute
      Cardiac Ischemia Time-Insensitive Predictive Instrument and the Thrombolytic
      Predictive Instrument are two decision-support tools designed to address this
      need. The instruments have been shown to improve some measures of the
      appropriateness of and time to emergency department triage. Prospective trials
      will be completed soon that will examine their effects on morbidity and
      mortality.

PMID- 11958441
TI  - Ambulatory electrocardiographic monitoring: use of the implantable loop recorder
      in the evaluation of syncope.
AB  - Syncope may be related to a large spectrum of medical and psychologic disorders,
      yet the precise etiology is often difficult to determine. Although the evaluation
      of syncope involves extensive testing, nearly 50% of these individuals remain
      without definitive diagnosis. Because of the infrequent and unpredictable nature
      of syncope, many ambulatory screening techniques are not suited to diagnose
      syncope. The use of an implantable loop recording device provides continuous
      monitoring of heart rate and rhythm during syncopal events and may help
      clinicians arrive at a more precise diagnosis in a more timely manner. The Reveal
      Plus implantable loop recorder (ILR) (Medtronic USA, Minneapolis, Minn) has
      demonstrated its clinical utility in evaluating syncope and drug-refractory
      seizure disorders.

PMID- 11958442
TI  - Ventricular assist devices: developing and maintaining a training and competency
      program.
AB  - Ventricular assist devices (VADs) have made it possible for patients with end
      stage heart failure to survive until a donor heart is available. In addition to
      serving as a bridge to transplantation, evolving indications for VADs include
      bridge to recovery and destination therapy. There are many VAD programs, but in
      the majority of programs only a small number of devices are implanted each year.
      Low volume poses a challenge in terms of provision of comprehensive education and
      training for nurses who will care for patients with VADs and in terms of
      maintaining competency to care for these patients. This article briefly addresses
      current VAD technology and VAD program development. The major focus is on the
      education and competency challenges and solutions the authors have experienced as
      infrequent users of VAD technology.

PMID- 11958443
TI  - Wearable defibrillator.
AB  - Technological advances have increased life expectancy and improved quality of
      life for patients with heart disease. A new device, called the wearable
      defibrillator, is designed to provide monitoring and defibrillation capability
      for patients who have had an infarct and those awaiting heart transplantation.
      These two populations of patients are at increased risk of sudden cardiac death.
      This external wearable apparatus continuously monitors a patient's heart rhythm.
      The monitor is programmed to recognize the individual's heart rhythm. If the
      heart rhythm changes and meets criteria for a lethal dysrhythmia, the monitor
      will provide a series of alarms to the patient and bystanders. If the patient
      fails to respond to the alarms, because of loss of consciousness, the system
      delivers a shock to treat the life-threatening dysrhythmia. Although still in the
      investigational phase, this device holds promise as temporary protection for
      patients at risk for sudden cardiac death.

PMID- 11958444
TI  - Psychosocial impact of the implantable cardioverter defibrillator: nursing
      implications.
AB  - Sudden cardiac death (SCD) remains a significant problem despite an overall
      reduction in other cardiac related deaths in recent years. Research supports the
      use of the implantable cardioverter defibrillator (ICD) as an effective means of
      treating dangerous ventricular tachydysrhythmias to prevent SCD. The issue that
      demands increasing attention is the psychologic experience of ICD recipients.
      Although the ICD is clearly a technological success, there is evidence that
      recipients experience strong physical and emotional reactions to the device. Such
      quality of life issues are worthy of a multidisciplinary effort directed at
      facilitating patient acceptance and adaptation to technology that although
      potentially life-saving, may also be unpredictable and anxiety provoking.

PMID- 11958445
TI  - Outpatient hemodynamic monitoring of patients with heart failure.
AB  - Effective management of patients with heart failure is guided by hemodynamic
      indices that may provide more objective evidence of cardiovascular status than
      physical signs and symptoms and the chest radiograph. Quantitative hemodynamic
      data obtained without the need for hospitalization supplements physical
      assessment findings, daily weights, and functional status classification and
      provides objective data for optimization of therapies and prevention or reduction
      of hospitalizations. The current health care climate is characterized by
      shrinking health care reimbursement and increased emphasis on patient-centered
      care focused on enhancing quality of life and patient satisfaction. In this
      climate, devices such as an implantable right ventricular hemodynamic monitor and
      impedance cardiography may improve nursing and medical management, promote
      appropriate use of resources, and contribute to enhanced quality of care and
      patient quality of life.

PMID- 11958446
TI  - Management of heart failure: use of biventricular pacing.
AB  - Congestive heart failure (CHF) is a clinical syndrome that affects more than 4
      million people in the United States. The grim prognosis for this population has
      led to a search for new therapies to treat CHF. Resynchronization of the
      ventricles is one such therapy. The pathophysiology associated with conduction
      defects and the evolution of the use of pacing technologies for this patient
      population will be discussed. Early data have been encouraging, suggesting that
      patients may gain important hemodynamic, functional, and quality-of-life
      improvements with biventricular pacing.

PMID- 11958447
TI  - Left ventricular splints and wraps for end-stage heart failure: a new approach in
      the new millennium.
AB  - The epidemic of heart failure and its subsequent effect on public health policy
      is escalating. Cardiac transplantation continues to be limited by the shortage of
      donor organs, and the current generation of mechanical circulatory support
      devices has not yet approached the goal of destination therapy. A better
      understanding of the role of left ventricular remodeling in the development of
      heart failure has resulted in novel surgical therapies and devices that may
      reverse or retard the remodeling process.

PMID- 11958448
TI  - Advanced cardiac life support for the new millennium.
AB  - The American Heart Association has been the recognized source for Advanced
      Cardiac Life Support (ACLS) education for the past three decades. Since the first
      ACLS course, numerous revisions have been made to the management algorithms based
      on evolving scientific evidence. The last revisions made in August 2000 were the
      first international guidelines published. These guidelines reflect the intense
      review and analysis of scientific work and emphasize the importance of evidence
      based therapies. This article outlines the major changes to ACLS guidelines for
      dysrhythmias, acute coronary syndromes, and acute stroke management.

PMID- 11958449
TI  - Ranaviruses (family Iridoviridae): emerging cold-blooded killers.
AB  - Although possessing novel replicative and structural features, the family
      Iridoviridae has not been as extensively studied as other families of large, DNA
      containing viruses (e.g., poxviridae and herpesviridae). This oversight most
      likely reflects the inability of iridoviruses to infect mammals and birds, and
      their heretofore low pathogenicity among cold-blooded animals and invertebrates.
      In fact, the original frog virus isolates (e.g., frog viruses 1-3) would likely
      have been considered orphan viruses since they were isolated from apparently
      healthy frogs. However, recent disease outbreaks among commercially and
      recreationally important fish, cultured and wild frogs, and endangered
      salamanders has challenged this benign view and have implicated several members
      of the genus Ranavirus as pathogens. This review explores three facets of
      ranavirus biology. In the first the salient features of ranavirus replication are
      summarized using frog virus 3 as a model. Secondly, criteria for characterizing
      new ranavirus isolates, based on biochemical (viral protein profiles, DNA
      restriction fragment length polymorphisms, and nucleotide sequence analysis),
      ecological (host range, tissue tropism), and clinical considerations, are
      detailed. Lastly, the principal agents of ranavirus-mediated disease and immune
      responses to these viruses are discussed. In light of the above, it is clear that
      ranaviruses are no longer orphan viruses, and that they have a significant impact
      on diverse populations of ectothermic animals.

PMID- 11958451
TI  - Phylogenetic analysis of serotype A foot-and-mouth disease virus isolated in
      India between 1977 and 2000.
AB  - The genetic diversity among the Indian serotype A Foot-and-mouth disease virus
      (FMDV) isolates sampled over a period of 24 years (1977-2000) was studied by
      sequencing the VP1 gene. In the phylogenetic tree, constructed from 83 Indian and
      37 other available sequences, the FMDV type A isolates were distributed into 10
      major genotypes (designated as I-X). The Indian isolates were distributed in 4
      genotypes (I, IV, VI and VII), and co-circulation of at least 2 genotypes (VI and
      VII) in different states of the country in recent years is evident from the
      result. The study also revealed differential geographic distribution of
      genotypes, for example, some (genotypes I and VII) were recovered from large
      geographical areas, some time even across the continents, suggesting the spread
      of the viruses beyond continental barriers. Localization of genotypes restricting
      to a particular country (genotypes III and X) was also observed in the study. The
      genetic diversity in the field isolates has been discussed in relation to the
      amino acid substitutions at the known antigenic sites. This work provides
      valuable insights into the epidemiological situation of type A FMDV in India and
      necessary information in the selection of suitable vaccine strain(s), if
      required, for the National FMD control program.

PMID- 11958450
TI  - Host cell proteins binding to the encapsidation signal epsilon in hepatitis B
      virus RNA.
AB  - The highly conserved encapsidation signal (epsilon) of hepatitis B viral (HBV)
      pregenomic RNA has been reported as an essential component for encapsidation and
      protein priming of HBV polymerase. Here, we report that two HBV epsilon RNA
      binding host proteins (80 and 43 kDa) and a copurifying protein (100 kDa) were
      purified and characterized by the combined methods of UV cross-linking analysis
      with the epsilon RNA and column chromatography. Amino-terminal microsequencing
      showed that 80- and 43-kDa proteins were identified as the heterodimeric nuclear
      factor of activated T cells (NF90/NF45) and 100 kDa as a molecular chaperone, the
      GRP94. The heterodimeric factor interacted preferentially with the upper-bulge
      region of HBV epsilon RNA helping the HBV polymerase bind the lower-bulge region.
      Using in vitro protein priming analysis, the initial oligonucleotide of the
      protein-priming product was deduced as 5'-GAAC-3', which is the complementary
      sequence of both regions of DR1 and epsilon in the pregenomic RNA. Previously, we
      also proposed that the GRP94 was associated with HBV polymerase in the human
      liver cell HepG2. These results suggest that the heterodimeric factor plays an
      important role in the priming activity of HBV polymerase.

PMID- 11958452
TI  - Effect of multiple freezing and thawing of serum on TT virus and hepatitis B
      virus DNA positivity.
AB  - This study was done to determine the effect of freezing and thawing of serum on
      the stability of TTV and HBV DNA levels. Seven TTV DNA positive samples were
      randomly selected among the sera having HBV DNA with concentrations ranging from
      12 pg/ml to 4162 pg/ml and they were frozen and thawed up to eight times and then
      analyzed for changes on TTV- and HBV DNA levels. TTV DNA positivity and HBV DNA
      concentrations were tested by using semi-nested PCR and Digene hybrid capture
      system, respectively. Seven cycles of freezing and thawing did not significantly
      change HBV DNA concentrations and TTV DNA positivity in any of the samples
      tested. After eight cycles, only three samples were tested, and all were positive
      for HBV DNA, but negative for TTV DNA. Our results show that both TTV- and HBV
      DNA positives continued until the seventh cycle of freezing and thawing in all
      samples tested.

PMID- 11958453
TI  - Mutation of the herpes simplex virus 1 KOS UL45 gene reveals dose dependent
      effects on central nervous system growth.
AB  - The herpes simplex virus type 1 (HSV-1) UL45 gene encodes an 18 kDa virion
      envelope protein whose function remains unknown. Previous studies using a UL45
      null mutant, UL45A, demonstrated that deletion of the UL45 gene altered plaque
      size in Vero and HeLa cells, but was not essential for replication in these cell
      types. The goal of this study was to determine if mutation of the UL45 gene
      influenced virus growth in the CNS. Two UL45 mutants, as well as a repaired
      revertant virus, were constructed and tested for their ability to cause
      encephalitis and replicate in the CNS. The UL45 mutants were not lethal when 1 x
      10(3) pfu were injected intracerebrally into Balb/c mice. In contrast, at inocula
      greater than 1 x 10(3), the UL45 mutants were lethal. In vivo growth curves
      derived from mice inoculated intracerebrally with 1 x 10(3) pfu of virus revealed
      that the mutants grew poorly compared to wild type or revertant viruses. These
      results suggest that the 18 kDa UL45 gene product is required for efficient
      growth in the central nervous system at low doses. We propose that the UL45 gene
      may play an important role under the conditions of a naturally acquired
      infection.

PMID- 11958454
TI  - Genus Coltivirus (family Reoviridae): genomic and morphologic characterization of
      Old World and New World viruses.
AB  - We report a genomic and morphologic study of the European Eyach (EYA) virus
      (genus Coltivirus, family Reoviridae) and a comparative analysis with the
      American Colorado tick fever (CTF) virus (the type species of the genus). The
      previously established, but distant, antigenic relationship between these viruses
      was strengthened by genetic findings (presence of cognate genes, amino acid
      identity between 55 and 88%, similar conserved terminal motifs, suspected read
      through phenomenon in segment 9 of both viruses) and by indistinguishable
      ultramicroscopic morphologies. Moreover, putative constitutive modifying enzyme
      activities were suspected to be carried out by homologous viral proteins (RNA
      dependent RNA polymerase, methyl/guanylyl transferase, NTPase). These findings,
      together with the comparative analysis to genomes of southeast Asian isolates,
      support the recent classification of arboviruses with 12 segments of dsRNA within
      two distinct genera (genus Coltivirus and genus Seadornavirus) and raise
      interesting questions about the evolutionary origins of coltiviruses. The
      previously proposed hypothesis that EYA virus was derived from an ancestral virus
      introduced in Europe with the migration of lagomorphs from North-America, would
      imply a divergence date between American and European isolates of over 50 million
      years ago (MYA). This analysis allows for the first time to propose an
      evolutionary rate for virus dsRNA genomes which was found to be in the order of
      10(-8) to 10(-9) mutations/nt/year, a rate similar to that of dsDNA genomes.

PMID- 11958455
TI  - Molecular variability of the P3-6K1 genomic region among geographically and
      biologically distinct isolates of Plum pox virus.
AB  - To evaluate molecular variability in the 5' region of the Plum pox virus (PPV)
      genome, a fragment spanning the C-terminal part of P3, the complete 6K1 and start
      of the CI gene in 12 Slovak and French PPV isolates was amplified in IC-RT-PCR
      and sequenced. Computer analysis of obtained and previously published sequences
      showed rather substantial differences among isolates of PPV-M and D subgroups
      (percentage of nucleotide identity ranged from 85.65 to 87.68%). There was a
      relatively low percentage of heterogeneity among isolates within the same
      subgroup. Amino acid multiple sequence alignment showed a total of 14 conserved
      subgroup-specific amino acid positions among PPV-M and D isolates in the examined
      region. The geographical origin of the isolates was not correlated with their
      phylogenetic clustering. No reasonable correlation could be established between
      amino acid substitutions and host species and/or biological properties of
      isolates. The present IC-RT-PCR detection method targeting a 5' region of the PPV
      genome, followed by simple RFLP subgroup determination, could enhance
      conventional CP-based techniques, especially with peculiar isolates. Using this
      approach, the Slovak isolate BOR-3 was found to be a natural recombinant between
      a D and an M PPV-type.

PMID- 11958456
TI  - Identification of human homologues of the mouse mammary tumor virus receptor.
AB  - Human breast tumors contain DNA sequences with high homology to the Mouse Mammary
      Tumor Virus (MMTV) env gene. env encodes the membrane glycoprotein that binds to
      the MMTV receptor (Mtvr) in mouse tissues and is required for infection. If
      humans become infected with MMTV, identification of a human Mtvr might shed light
      on the mechanism of infection. Here, we identified two human genes, Mtvr1 and
      Mtvr2, encoding proteins highly related to the mouse receptor. Mtvr-related
      sequences were also detected in other mammalian species. Thus, zoonotic
      transmission of MMTV is a real possibility given the existence of highly
      homologous MMTV receptors.

PMID- 11958457
TI  - Comparison of molecular and immunological typing of isolates of Rice yellow
      mottle virus.
AB  - Isolates of Rice yellow mottle virus (RYMV) were typed at the molecular level
      through the sequences of the open reading frame (ORF) 4 (coding for the coat
      protein) and ORF1 (coding for the movement protein), and serologically by means
      of polyclonal and monoclonal antibodies. The overall patterns of diversity shown
      by molecular and serological analyses were similar: East-African isolates
      differed from West-African ones, and the West-African isolates from forest
      differed from the savannah ones. Each major strain had a different serological
      profile. However, molecular typing was more discriminating than immunological
      typing since several sequence variants belonged to the same serotype. In rare
      instances, there were explainable discrepancies between molecular and serological
      typing. Two amino acids at positions 115 (alanine vs threonine) and 191 (valine
      vs threonine) consistently discriminated between the major serotypes. These
      positions were located in antigenic sites as revealed by Spot-scan method and
      were recognised by discriminating monoclonal antibodies. One shared epitope,
      lying within a conserved region, may be responsible for the cross-reactivity
      between RYMV isolates. A rationale for the correlation between molecular and
      immunological typing of RYMV and other sobemoviruses is proposed.

PMID- 11958458
TI  - Immunization with a plasmid DNA expressing rinderpest virus hemagglutinin protein
      protects rabbits from lethal challenge.
AB  - Rinderpest virus haemagglutinin (H) protein was expressed in eukaryotic cells and
      the plasmid encoding H gene was used for immunization of rabbits. The immunized
      rabbits were completely protected from lethal challenge with virulent lapinized
      rinderpest virus. Similar results were also observed in rabbits vaccinated with
      tissue culture rinderpest (TCRP) vaccine. About 80% of control rabbits vaccinated
      with empty vector (mock-vaccinated) died after challenge. The thermal reactions
      and clinical symptoms were less intense in H-DNA vaccinated rabbits as compared
      to the other two groups. Marked lymphopenia was observed in TCRP and mock
      vaccinated rabbits after challenge, however, the H-DNA vaccinated rabbits showed
      lymphocytosis following challenge. The appearance of lymphocytosis in H-DNA
      vaccinated rabbits is an interesting finding which needs further investigation.

PMID- 11958459
TI  - The C-terminal regions of the envelope glycoprotein gp2 of equine herpesviruses 1
      and 4 are antigenically distinct.
AB  - The unusual mucin-like high molecular mass (Mr) glycoprotein 2 (gp2) has only
      been described in the equid alphaherpesviruses, among which there is considerable
      antigenic cross-reactivity. Equine herpesvirus 1 (EHV-1) gp2 is cleaved into a
      highly glycosylated N-terminal subunit and a 42 kDa C-terminal cleavage product.
      In order to investigate their antigenic recognition by horses naturally infected
      with EHV-1 and/or equine herpesvirus 4 (EHV-4), the C-terminal cleavage product
      and high Mr gp2 were affinity purified. Cross-reactivity between EHV-1 and EHV-4
      was observed for the high Mr gp2 using Western blotting. In contrast only horses
      with antibodies to EHV-1 detected the 42 kDa EHV-1 gp2 C-terminal cleavage
      product. This phenomenon was evident in pooled sera from adult horses and also in
      foals that had demonstrated seroconversion due to EHV-1 infection. The results
      indicate that the C-terminal region of EHV-1 gp2 is antigenically distinct from
      that of EHV-4 gp2 and can be detected only after an EHV-1-specific immune
      response.

PMID- 11958460
TI  - A New York isolate of Soil-borne wheat mosaic virus differs considerably from the
      Nebraska type strain in the nucleotide sequences of various coding regions but
      not in the deduced amino acid sequences.
AB  - A wheat-infecting furovirus found in Tompkins County, New York, U.S.A. was
      identified as a strain of Soil-borne wheat mosaic virus (SBWMV) by means of
      sequence analyses of portions of its RNA 1 and 2. The nucleotide sequences of
      several of its genes differed by c. 9 to 12% from those of the corresponding
      genome regions of the Nebraska type strain of SBWMV. The deduced amino acid
      sequences of the putative translation products, however, suggested much closer
      relationships. Thus, the amino acid sequences of the coat proteins of the two
      virus strains were 100% identical despite the fact that their coding regions
      differed in as many as 68 nucleotide positions. The New York (NY) strain of SBWMV
      is possibly closely related to an isolate from Illinois for which so far only the
      nucleotide sequences of its coat protein gene and the 5' untranslated region of
      its RNA 2 are known.

PMID- 11958461
TI  - Epitope mapping of Grapevine virus A capsid protein.
AB  - Previously characterized monoclonal antibodies (MAbs) to Grapevine virus A (GVA)
      showed a differential reactivity against intact or partially destabilized virus
      particles [2]. In the present study, this differential reactivity was confirmed
      and several peptides reacting with a panel of four different antibodies were
      identified by the PEPSCAN method of epitope mapping. Oligopeptide sequences
      comprised between coat protein residues 61 (V) and 72 (T) were recognized by all
      the antibodies tested. One of these peptides (VGPKASK) was also reactive when
      expressed on recombinant phage particles as a fusion protein with protein pVIII.
      The specificity of this sequence for antibody binding was also demonstrated by
      competitive-ELISA using one of the GVA MAbs. The results of this study suggest
      that GVA particles carry a highly structured epitope centered on a common peptide
      region of the coat protein sequence.

PMID- 11958462
TI  - The complete sequence of Oat mosaic virus and evidence for deletion and
      duplication in RNA2.
AB  - The complete nucleotide sequence of a UK isolate of oat mosaic virus (OMV) was
      determined. RNA1 was 7550 nt long with one large open reading frame potentially
      encoding a polyprotein of 262.8 kDa with features typical of bymoviruses. RNA2
      was 2284 nt in length, substantially smaller than those of other bymoviruses
      sequenced. It appeared that most of the P2 region had been deleted during
      repeated mechanical transmission of the isolate. The 3'-UTR of RNA2 was very long
      (> 1.25 kb) and proved to have a 532 nt slightly overlapping repeat. Phylogenetic
      analysis confirmed that OMV is an independent member of the genus Bymovirus.

PMID- 11958463
TI  - Tat protein expression in MDBK cells does not confer susceptibility to bovine
      immunodeficiency virus.
AB  - The ability of BIV strain R29 to infect bovine cell lines in the presence or
      absence of a functional lentiviral Tat protein is described. Jembrana disease
      virus (JDV) Tat protein was stably expressed in MDBK cells. No viral replication
      could be detected in this cell line after infection with BIV R29. Transfection of
      MDBK cells and MDBK Tat expressing cells with BIV R29 proviral DNA established
      that BIV R29 could not replicate in MDBK cells. Whether viral entry into MDBK
      cells is also a block to BIV R29 infection of MDBK cells has yet to be
      established.

PMID- 11958464
TI  - Serological and coat protein sequence studies suggest that necrosis disease on
      sunflower in India is caused by a strain of Tobacco streak ilarvirus.
AB  - Serological and coat protein sequence studies were conducted to identify an
      ilarvirus associated with necrosis disease on sunflower in India. In electroblot
      immunoassay, sunflower ilarvirus reacted strongly only with antiserum to Tobacco
      streak virus (TSV). The coat protein gene of sunflower ilarvirus was cloned and
      sequenced. The sequence analyses also showed that the CP gene was most closely
      related to TSV, the member of subgroup I of Ilarvirus. The sunflower ilarvirus CP
      shared 90% amino acid sequence identity with TSV. On the basis of serological
      relatedness and sequence identity, it is proposed that the sunflower ilarvirus
      from India should be considered a strain of TSV belonging to subgroup I and
      designated as TSV-SF. This is the first report of the molecular characterization
      of TSV on sunflower from the Indian subcontinent.

PMID- 11958465
TI  - Importance of thymidine kinase activity for normal growth of lumpy skin disease
      virus (SA-Neethling).
AB  - In order to study the importance of an intact thymidine kinase (TK) gene for the
      vaccine strain of a southern African capripoxvirus, namely, lumpy skin disease
      virus (LSDV) (type SA-Neethling), a TK disruption recombinant was generated
      expressing the Escherichia coli beta-galactosidase (lacZ) reporter gene. A
      comparative growth study of the recombinant and wild-type (wt) LSDV in TK
      positive primary and secondary cells and TK-negative secondary cells was
      performed. It was found that although recombinant and wt virus both grew in TK
      positive cells without selection, the recombinant was unable to grow in TK
      negative cells (with or without selection), indicating that TK activity is
      important, if not essential, for normal growth of LSDV.

PMID- 11958466
TI  - Environmental toxicology: polychlorinated biphenyls impair TNF-alpha release in
      vitro.
AB  - Tumour necrosis factor (TNF-alpha) was induced by bacterial lipopolysaccharides
      (LPS)/phytohemagglutin (PHA) stimulated human whole blood in vitro. Levels of TNF
      alpha were evaluated by enzyme-linked immunosorbent assay. Blood samples treated
      with polychlorinated biphenyls (PCB 77, PCB 126) exhibited impairment of TNF
      alpha release: 50 pg/microl PCB reduced by up to 66% and 500 pg/microl PCB
      reduced by up to 93% the TNF-alpha release compared with the controls.

PMID- 11958467
TI  - Dog bite wounds in dogs and cats: a retrospective study of 196 cases.
AB  - The age, type, etc., time of injury, body areas injured, treatment modalities and
      mortality rates were reviewed in 185 dogs and 11 cats that were bitten by dogs.
      Male dogs were more frequently bitten than females, and small dogs (< or = 10 kg)
      were not only the most common victims but also were more likely to suffer
      multiple injuries. Mortality occurred only in cases with thoracic or abdominal
      injuries. Exploratory thoracotomy, performed in some of the cases presented with
      penetrating thoracic injury, did not prove to alter prognosis. Cats are not as
      frequently bitten as dogs, and are often younger than the mean age of cats in the
      overall hospital population.

PMID- 11958469
TI  - Effects of hyperinsulinaemia under euglycaemic condition on liver fat metabolism
      in dairy cows in early and mid-lactation.
AB  - The objective was to examine the effects of insulin under euglycaemic conditions
      on liver long chain fatty acids (LCFA) metabolism with special focus on the
      aetiology of hepatic lipidosis in early lactation. A 4-day hyperinsulinaemic
      euglycaemic clamp (clamp) was conducted on four dairy cows starting in weeks 4
      and 17 postpartum. Insulin was infused continuously (1 microg/kg BW per h) and a
      50% glucose solution was infused to maintain euglycaemia. Liver biopsies were
      taken 6 days before, the last day of, and 5 days after the clamp, and blood
      samples were taken in the same period. In the liver tissue, the relative
      triglyceride content decreased (P < 0.01) and the glycogen content increased (P <
      0.0001) in response to the clamp. Hepatic in vitro palmitate oxidation capacity
      was lowest during the clamp period and could be explained by a significant
      decrease in incomplete oxidation (ketogenesis) (P < 0.04) and a tendency to a
      decreased complete oxidation of palmitate (P < 0.10). Plasma non-esterified fatty
      acids concentration was decreased during the clamp in early lactation (P < 0.05)
      but there was no effect on the mid-lactation clamp. The present study shows that
      increased insulin under euglycaemic conditions seems to depress hepatic LCFA
      oxidation capacity. However, in terms of preventing hepatic lipidosis, the anti
      lipolytic effect of insulin on adipose tissue, which results in decreased
      mobilization of and hence hepatic load with LCFA, appears more important.

PMID- 11958468
TI  - Effects of synthetic progestagens on the mRNA expression of androgen receptor,
      progesterone receptor, oestrogen receptor alpha and beta, insulin-like growth
      factor-1 (IGF-1) and IGF-1 receptor in heifer tissues.
AB  - Synthetic progestagens like melengestrol acetate (MGA) are widely used for
      oestrus synchronization and for growth promotion in cattle production. The
      metabolic effects exceed its primary potency as a progestagen. It is speculated
      that MGA stimulates follicle development and thereby endogenous oestrogen
      production, but inhibits ovulation. To investigate the dose-dependent effects on
      mRNA expression levels, six heifers were fed for 8 weeks with different levels of
      MGA (0.5, 1.5, 5 mg) daily and two heifers served as controls. The expression of
      steroid receptor mRNA [androgen receptor (AR), progesterone receptor (PR),
      oestrogen receptor (ER) ERalpha and ERbeta], insulin-like growth factor-1 (IGF-1)
      and its receptor were quantified in liver, neck (m. splenius) and shoulder
      muscularity (m. deltoideus). Plasma concentrations of IGF-1 were quantified by
      radioimmunoassay. In treated animals the MGA plasma levels were elevated over the
      complete treatment period, corresponding to the MGA treatment concentrations. IGF
      1 concentrations of control animals were at constant levels. Plasma levels for
      oestradiol (E2) and IGF-1 were increased in the low MGA treatment group.
      Overdosed MGA decreased progesterone (P4) and E2 levels. To quantify the IGF-1
      and all receptor mRNA transcripts, sensitive and reliable real-time reverse
      transcription-polymerase chain reaction (RT-PCR) quantification methods were
      developed and validated in the LightCycler. A dose-dependent relationship between
      increasing MGA concentration and mRNA expression was observed in liver for AR and
      IGF-1 receptor, and in neck muscularity for IGF-1. ERalpha in liver and neck
      muscle showed a trend of increasing expression.

PMID- 11958470
TI  - Glucose or essential amino acid infusions in late pregnant and early lactating
      Simmenthal cows failed to induce a leptin response.
AB  - To assess the leptin response to metabolic challenges, three Italian Simmental
      cows were infused for 6 h: with (a) saline (control); (b) glucose; and (c) amino
      acid solutions according to a 3 x 3 Latin square experiment. The infusions were
      carried out at the 36th week of pregnancy, and the second and 12th week of the
      following lactation. At each of the three infusion periods, blood samples were
      collected from the jugular vein before and 15, 30, 120, 180, 240, 300 and 360 min
      after the beginning of each infusion. All samples were analysed for leptin,
      insulin, glucagon, growth hormone (GH), glucose, non-esterified fatty acids
      (NEFA) and urea. The physiological phase of the cows significantly affected the
      basal concentrations of insulin, glucagon, urea and NEFA. The infusion of both
      glucose and the amino acid solutions did not affect leptin concentrations.
      Insulin response was significantly increased when animals were infused with the
      glucose solution and, within treatment, the greatest response was observed at the
      12th week of lactation. The greatest glucagon response was observed when infusing
      the amino acid solution. Urea response to all treatments increased from the dry
      period to the 12th week of lactation. The GH and NEFA responses were not affected
      by treatments. The Multi Species radio-immunoassay used in this study showed a
      lower sensitivity for ruminant leptin which may partially explain the lack of
      significant leptin variations. However, it can be hypothesized that leptin
      variations around parturition can be affected by the negative energy balance, and
      leptin release is not acutely affected by glucose and amino acid availability. In
      addition, no short-term relationship were found between insulin, glucagon and GH
      and leptin release in Italian Simmental cows during the dry period and early
      lactation.

PMID- 11958472
TI  - Prevalence, distribution and factors associated with the presence and the
      potential for malignancy of cutaneous neoplasms in 174 dogs admitted to a clinic
      in northern Greece.
AB  - One hundred and seventy-four dogs diagnosed with cutaneous neoplasms in the
      Animal Medical and Surgical Clinic, Faculty of Veterinary Medicine, Aristotle
      University of Thessaloniki, were studied. Thirty-one types of neoplasm were
      diagnosed, among which mast cell tumours (13.8%), hepatoid gland adenomas (9.8%),
      lipomas (5.7%) and histiocytomas (5.7%) were the most common. The prevalence of
      epithelial, mesenchymal, lymphohistiocytic and melanocytic tumours was 47.7,
      40.8, 8.6 and 2.9%, respectively. Potentially malignant neoplasms were less
      frequently recorded than benign neoplasms. The tumours were single (80.5%) or
      multiple (19.5%) and located on the head and neck (18.4%), the body trunk
      (49.4%), the limbs (25.9%) or at multiple sites (6.3%). The factors evaluated in
      multivariable logistic regression models for possible association with the odds
      of a tumour's potential for malignancy included the age, the sex and the breed of
      the dog, as well as the histological type of the neoplasm. Dogs with mesenchymal
      tumours had two times higher odds of potential for malignancy than those with
      epithelial tumours. In contrast, dogs with either lymphohistiocytic or
      melanocytic tumours did not have increased risk of malignancy compared with dogs
      with epithelial tumours. The odds of tumour malignancy linearly increased with
      increasing age of the dog by a factor of 1.1 per year. Finally, the effect of the
      sex and the breed of the dog on the risk of developing cutaneous neoplasms was
      investigated in an age-matched case-control sample of 348 dogs by conditional
      logistic regression analysis. The odds of neoplasm presence were two times higher
      in pure bred dogs than in mongrels but did not differ between cross-breeds and
      mongrels.

PMID- 11958471
TI  - Small intestinal morphology and disaccharidase activities in early-weaned piglets
      fed a diet containing spray-dried porcine plasma.
AB  - The purpose of this study was to test whether dietary spray-dried porcine plasma
      (SDPP) in early-weaned piglets prevents small intestinal villus atrophy by
      trophic or protective activity. Fifty-four weaned, 18-day-old piglets were used
      to determine the effect of dietary SDPP on small intestinal villus length, crypt
      depth, enterocyt mitotic activity and brush border enzyme activities during the
      first week after weaning. The piglets were offered a diet containing either 8%
      SDPP or 8% casein. At 2 and 7 days after weaning, piglets were anaesthetized to
      provide samples of the small intestinal wall and killed immediately afterwards.
      There were no differences in daily gain and daily feed intake between the two
      dietary treatments. At day 2 after weaning, all piglets showed a marked reduction
      in villus height when compared with baseline values. In all piglets, small
      intestinal enterocyte mitotic activity had decreased by day 2 and was increased
      again on day 7. There were no significant effects of dietary SDPP on small
      intestinal villus length, crypt depth and enterocyt mitotic activity. This
      indicates that SDPP has no trophic effect on the small intestinal mucosa and that
      it does not protect against the damaging effect on the small intestinal villi
      that is associated with the process of weaning. There was no effect of SDPP on
      lactase-, sucrase- or maltase-specific activities that are a measure of the
      digestive function of the small intestine. It can be concluded that SDPP versus
      casein has no effect on small intestinal morphology and disaccharidase activities
      in early weaned piglets kept under low infection pressure.

PMID- 11958473
TI  - Delayed acute capture myopathy in three roe deer.
AB  - Delayed acute capture myopathy is the term used to describe the clinical syndrome
      observed in three roe deer captured by drive-nets and transported to an enclosure
      for scientific purposes. The animals died 48 h, 60 h and 8 days after being
      captured. The simultaneous deaths coincided with a previous episode of deliberate
      human disturbance. The histopathological findings were indicative of acute
      myopathy and myoglobinaemic nephrosis. These could be related to an ataxic
      myoglobinuric syndrome brought on by capture and transport operations. The lack
      of clinical signs and negative prognosis indicators in the period between capture
      and just before death. the absence of gross muscular lesions in the animal that
      died after 8 days post-capture, the simultaneous deaths of animals captured at
      different times and the evidence of deliberate human disturbance in the enclosure
      are suggestive of death triggered by a second stress episode.

PMID- 11958474
TI  - Concentration of enrofloxacin and its metabolite ciprofloxacin in canine matrices
      of the locomotor system.
AB  - Due to its pharmacodynamic and pharmacokinetic properties, the use of
      enrofloxacin may be indicated in canine osteomyelitis, but there is insufficient
      data on its distribution within the musculoskeletal tissues. The dogs used in
      this study were 31 regular veterinary orthopaedic patients. Four hours after
      their oral or subcutaneous treatment with 10 mg/kg enrofloxacin (Baytril; Bayer,
      Leverkusen, Germany) once daily for 1 or 3 days, the concentration of
      enrofloxacin and its main metabolite ciprofloxacin was quantified in plasma,
      bone, musculature and other matrices of the locomotor system by high pressure
      liquid chromatography with fluorescence-detection after homogenization and solid
      phase extraction of the samples. By oral or subcutaneous administration of
      enrofloxacin once daily for 3 days, higher concentrations of the active
      constituents in the samples were achieved than by single treatment. Nevertheless,
      even after single injection, minimal inhibitory enrofloxacin concentrations of up
      to 0.5 microg ml or microg/g sample against most pathogens of osteomyelitis were
      exceeded. In the musculature, on average, higher concentrations of active
      constituents were detected than in less perfused matrices (bones and synovial
      membranes) at sampling time. The enrofloxacin diffusion into inflamed bone was
      higher compared with mechanically damaged bone, whereas for ciprofloxacin it was
      lower. In conclusion, a dosage of 10 mg/kg enrofloxacin is sufficient to exceed
      the minimal inhibitory concentrations in osteomyelitic bone against most
      pathogens that are sensitive in vitro, but clinical efficacy remains to be
      evaluated.

PMID- 11958475
TI  - Substance P afferent terminals innervate vagal preganglionic neurons projecting
      to the trachea of the ferret.
AB  - Airway disorders, such as asthma and chronic obstructive bronchitis, are, in
      part, due to abnormalities in the nervous control of the airways. However, the
      ultrastructural circuitry and neurochemical anatomy of afferents modulating the
      output of airway-related vagal preganglionic neurons (VPNs) in the nucleus
      ambiguus are poorly understood. We have examined the potential role of substance
      P (SP) immunoreactive afferents in the regulation of anatomically identified
      airway VPNs. Cholera toxin b-subunit conjugated to horseradish peroxidase was
      used as a retrograde cell body tracer to identify the central VPNs innervating
      the extra-thoracic trachea. Immunocytochemistry was employed to identify SP
      afferents. The external formation of the nucleus ambiguus was examined by
      electron microscopy using a simultaneous double labeling method. Cell bodies of
      tracheal VPNs were 31.7 +/- 1.18 x 23.0 +/- 1.3 microm (means +/- S.E.M.) in
      size, contained abundant endoplasmic reticulum, had a round nucleus with a
      prominent nucleolus, no satellite body and displayed somatic and dendritic
      spines. Somato-somatic appositions, somato-dendritic appositions without
      intervening glial processes and dendritic "bundling" commonly seen in esophageal
      motoneurons were not observed. The ultrastructural morphology of tracheal VPNs
      were also clearly distinguishable from pharyngeal and laryngeal motoneurons in
      other divisions of the nucleus ambiguus which lack somatic spines. These data are
      consistent with the hypothesis that differences in the ultrastructure and
      synaptology of the different divisions of the nucleus ambiguus may be associated
      with specific physiological functions. The mean size (+/- S.E.M.) of SP nerve
      terminals was 1.57 +/- 0.06 x 0.79 +/- 0.03 microm. SP terminals formed 17.5% of
      the axo-dendritic and 15.9% of the axo-somatic synapses which were observed upon
      retrogradely labeled tracheal VPNs. Synaptic contacts observed were both
      symmetric and asymmetric. These synaptic interactions define, in part, the
      neurochemical anatomy of neuronal circuits modulating vagal preganglionic control
      of tracheal functions.

PMID- 11958476
TI  - Activation of muscarinic M1 receptors by acetylcholine to increase glucose uptake
      into cultured C2C12 cells.
AB  - Regulation of glucose metabolism by cholinergic nervous activation has been
      demonstrated. In an attempt to evaluate the role of cholinergic receptor subtype
      in this regulation of glucose metabolism, we employed cultured myoblast C2C12
      cells to investigate the glucose uptake in the present study. Acetylcholine (ACh)
      enhanced the uptake of radioactive glucose into C2C12 cells at the concentration
      range of 0.001 to 1.0 micromol/l. This effect was suppressed by the muscarinic
      antagonist atropine. Effect of ACh on muscarinic receptors was further supported
      by the blockade of scopolamine, another classical antagonist. Thus, activation of
      muscarinic receptors to enhance the radioactive glucose uptake into C2C12 cells
      can be considered. Moreover, pirenzepine, the antagonist of muscarinic M1
      receptors, competitively antagonized the action of ACh in C2C12 cells. However,
      methoctramine at concentration sufficient to inhibit the muscarinic M2 receptors
      failed to produce similar effect. Similarly, 4-DAMP at effective concentration to
      block muscarinic M3 receptors lacked the influence. An activation of muscarinic
      M1 receptors seems responsible for the action of ACh in C2C12 cells.
      Pharmacological inhibition of phospholipase C by U73312 resulted in a
      concentration-dependent decrease in ACh-stimulated uptake of radioactive glucose
      into C2C12 cells. However, treatment with U73343, the inactive congener, failed
      to block the action of ACh. Moreover, both chelerythrine and GF 109203X
      diminished the action of ACh at concentrations sufficient to inhibit protein
      kinase C. Therefore, the obtained data suggest that increase of the glucose
      uptake evoked by ACh is mainly due to the activation of muscarinic M1 receptors
      in cultured myoblast C2C12 cells.

PMID- 11958477
TI  - Reduction of food intake following X-ray irradiation of rats--involvement of
      visceral afferent nerves.
AB  - Radiotherapy for malignant tumours often elicits anorexia or loss of appetite as
      an adverse effect. However, the mechanism for this is poorly understood. The
      present study was undertaken to investigate if visceral afferents are responsible
      for reduction of food intake following X-ray irradiation. Rats were exposed
      bilaterally to X-ray (10 MV) irradiation with total doses of 1.5, 3 and 6 Gy,
      using a high-energy electron linear accelerator at a dose rate of 4.9 Gy min(-1)
      X-ray irradiation of the whole body, abdomen or head with doses of 1.5, 3 and 6
      Gy reduced food intake in a dose-dependent manner. The reduction of food intake
      after X-ray irradiation of the whole body or abdomen was significantly greater
      than when only the head was irradiated. Reduction of food intake was observed for
      the first 4 days after 6 Gy X-ray irradiation of the abdomen, while it was
      observed only on the first day after the same 6-Gy irradiation of the abdomen in
      animals whose small-diameter afferents were ablated by capsaicin pre-treatment.
      These results suggested that the abdominal afferent nerves at least contribute to
      the reduction of food intake observed on second to fourth days after 6-Gy
      abdominal irradiation. Taken together, the present evidence suggests that the
      reduction of food intake following X-ray irradiation of the whole body or the
      abdomen is partly mediated via abdominal afferent nerves. Moreover, the results
      of X-ray irradiation to the head suggest that X-ray irradiation directly
      influences the central nervous system to reduce food intake.

PMID- 11958478
TI  - Nicotine-induced NO-mediated increase in cortical cerebral blood flow is blocked
      by beta2-adrenoceptor antagonists in the anesthetized rats.
AB  - Involvement of nitric oxide (NO) and beta-adrenoceptors in an increase in the
      cortical cerebral blood flow (CBF) following an intravenous (i.v.) injection of a
      small dose of nicotine which did not affect the systemic blood pressure in the
      rats was investigated. I.v. injection of nicotine (30 microg/kg) for 1 min
      produced a significant increase in CBF lasting for more than 20 min without a
      significant effect on the systemic blood pressure. I.v. injection of L-N(G)
      nitroarginine methylester (30 mg/kg) significantly attenuated nicotine-induced
      increase in the cortical CBF. The attenuation was reversed by i.v. injection of L
      arginine (300 mg/kg), suggesting an intimate role of nitric oxide (NO) in
      nicotine-induced increase in the cortical CBF. The nicotine-induced increase in
      the cortical CBF was significantly attenuated by propranolol (10 mg/kg, i.v.) and
      ICI 118,551 (a beta2-adrenoceptor antagonist, 10 mg/kg, i.v.) but not by
      metoprolol (a beta1-adrenoceptor antagonist, 10 mg/kg, i.v.). Beta2-adrenoceptors
      on presynaptic nitrergic nerves may be involved in nicotine-induced NO-mediated
      increase in the cortical CBF.

PMID- 11958479
TI  - Aldose reductase: an aldehyde scavenging enzyme in the intraneuronal metabolism
      of norepinephrine in human sympathetic ganglia.
AB  - The neurotransmitter norepinephrine is metabolized by monoamine oxidase into an
      aldehyde intermediate that is further metabolized to the stable glycol
      derivative, 3,4-dihydroxyphenylglycol (DHPG). In this study, the possible role of
      aldose reductase in reducing this aldehyde intermediate in human sympathetic
      neurons has been examined. DHPG is formed when norepinephrine is incubated with
      aldose reductase in the presence of monoamine oxidase. DHPG metabolism is
      inhibited by the monoamine oxidase inhibitor, pargyline which prevents the
      deamination of norepinephrine, and by the aldose reductase inhibitor AL 1576,
      which inhibits DHPG formation without affecting the deamination of
      norepinephrine. Although similar formation of DHPG was observed with human liver
      aldehyde reductase, the production of DHPG was more effective with aldose
      reductase than aldehyde reductase. Two peaks of reductase activity corresponding
      to aldose reductase and aldehyde reductase were observed when sympathetic ganglia
      were chromatofocused. Molecular modeling studies indicate that the energy
      minimized structure of 3,4-dihydroxymandelaldehyde bound to aldose reductase is
      similar to that of glyceraldehyde where the 2'-hydroxyl group forms hydrogen
      bonds with Trp111 and NADPH. These results suggest that aldose reductase may be
      important in metabolizing the potentially toxic aldehyde intermediate formed from
      norepinephrine in human sympathetic ganglia.

PMID- 11958480
TI  - A common origin of the very low frequency heart rate and blood pressure
      variability--a new insight into an old debate.
AB  - The purpose of this study was to assess the exact temporal and amplitude
      relationship between very low frequency heart rate variability waves and very low
      frequency blood pressure variability waves. We developed a computerized system
      based on a modified proportional-integral controller for the controlled increase
      of heart rate by isoproterenol. Heart rate and blood pressure were measured
      continuously in conscious tethered rats. Using time domain methods, we found that
      the very low frequency heart rate variability waves and the very low frequency
      blood pressure variability waves are irregular, while at the same time strikingly
      1:1 synchronized with each other. In 78% of the cases, the phase between the
      peaks of the very low frequency heart rate variability waves and very low
      frequency blood pressure variability waves was negative (blood pressure leads).
      Their amplitudes were linearly related with a degree of hysteresis. As blood
      pressure went up, heart rate went down. Our results suggest with a high degree of
      probability that the very low frequency heart rate variability waves do not cause
      very low frequency blood pressure variability waves, and that these two signals
      are probably driven by the same autonomic nervous system controller/oscillator.

PMID- 11958481
TI  - Electrical stimulation-induced alpha1- and alpha2-adrenoceptors-mediated
      contractions of isolated canine lymph nodes.
AB  - The contractile effects of alpha-adrenoceptor agonists and field electrical
      stimulation were investigated pharmacologically in canine isolated
      tracheobronchial lymph nodes. Addition of noradrenaline (NA), phenylephrine (Phe)
      and UK14,304 caused dose-related contractions of the isolated lymph nodes.
      Pretreatment with prazosin (3 x 10(-9), 3 x 10(-8) and 3 x 10(-7) M) shifted the
      concentration-response curve for phenylephrine to the right, whereas yohimbine (3
      x 10(-7) M) did not affect the contractile responses to phenylephrine. On the
      other hand, the concentration-response curve for UK 14,304 shifted to the right
      by treatment with yohimbine (3 x 10(-9), 3 x 10(-8) and 3 x 10(-7) M) but not by
      prazosin (3 x 10(-7) M). Field electrical stimulation (25 V, 0.7 ms, 16 Hz)
      produced contractile responses of the lymph nodes. The electrical stimulation
      induced contractions were completely reduced by pretreatment with tetrodotoxin
      (TTX) (3 x 10(-7) M) or bretylium (10(-6) M). Furthermore, phentolamine (10(-8),
      10(-7) and 10(-6) M), prazosin (3 x 10(-9) and 3 x 10(-8) M) and yohimbine (3 x
      10(-8) and 3 x 10(-7) M) significantly reduced the electrical stimulation-induced
      contractions in the preparations. The present findings suggest that there are
      both alpha1- and alpha2-adrenoceptors located on the smooth muscle cells in
      canine tracheobronchial lymph nodes, and that the adrenoceptors-mediated
      excitatory mechanisms of adrenergic innervation exist in the lymph nodes.

PMID- 11958482
TI  - Sodium conductance in cultured myenteric AH-type neurons from guinea-pig small
      intestine.
AB  - Whole-cell patch clamp methods were used to investigate sodium conductance in
      after-hyperpolarization-type (AH) enteric neurons in culture after dissociation
      from the myenteric plexus of guinea-pig small intestine. Inward current carried
      by Na+ (I(Na)) was identified and its current-voltage characteristics were
      compared with those for inward Ca2+ current (I(Ca)). The I(Na) current was a
      rapidly inactivating current relative to I(Ca). Application of tetrodotoxin (TTX)
      blocked I(Na) with an EC50 of 10.7 nM. Activation curves for I(Na) showed a rapid
      decrease in time to peak for test potentials from holding potentials of -80 mV to
      between -40 and -10 mV. Voltage-dependence of steady-state inactivation curves
      for I(Na) was fit to the Boltzmann equation with potential for half-inactivation
      (V(1/2)) = -55.6 mV and slope factor (k) = 6.4 mV. Steady-state inactivation for
      I(Ca) fit the Boltzmann equation with a V(1/2) = -38.9 mV and k= 14.4 mV.
      Kinetics for inactivation of I(Na) were voltage dependent at potentials between 
      70 and -30 mV and accelerated and became less voltage-dependent at more positive
      potentials. The time constant (tau) for inactivation at -70 mV was tau = 161 +/-
      23 ms and decreased to tau = 2.3 +/- 0.2 ms at -30 mV. Rapid acceleration of
      inactivation occurred between -50 and -40 mV. This was also the range where
      activation began. Recovery from inactivation with the membrane potential clamped
      at -100 or -80 mV was rapid and fit by a single exponential with tau = 7.3 +/-
      1.1 ms for -100 mV and 21.5 +/- 5.1 ms for -80 mV. The results suggest that AH
      type enteric neurons have only one type of Na+ channel that behaves like the
      "classical" voltage-gated tetrodotoxin-sensitive fast channel. The findings
      support the hypothesis that I(Na) current is an important factor in determination
      of excitability and firing behavior in AH neurons. I(Na) and I(Ca) together
      determine the properties of the rising phase of the spike and thereby contribute
      to global determinants of excitability as the neurons are exposed to multiple
      depolarizing and hyperpolarizing stimuli from synaptic inputs and mediators
      released from enteroparacrine cells.

PMID- 11958483
TI  - Projective ART for clustering data sets in high dimensional spaces.
AB  - A new neural network architecture (PART) and the resulting algorithm are proposed
      to find projected clusters for data sets in high dimensional spaces. The
      architecture is based on the well known ART developed by Carpenter and Grossberg,
      and a major modification (selective output signaling) is provided in order to
      deal with the inherent sparsity in the full space of the data points from many
      data-mining applications. This selective output signaling mechanism allows the
      signal generated in a node in the input layer to be transmitted to a node in the
      clustering layer only when the signal is similar to the top-down weight between
      the two nodes and, hence, PART focuses on dimensions where information can be
      found. Illustrative examples are provided, simulations on high dimensional
      synthetic data and comparisons with Fuzzy ART module and PROCLUS are also
      reported.

PMID- 11958484
TI  - A review of evidence of health benefit from artificial neural networks in medical
      intervention.
AB  - The purpose of this review is to assess the evidence of healthcare benefits
      involving the application of artificial neural networks to the clinical functions
      of diagnosis, prognosis and survival analysis, in the medical domains of
      oncology, critical care and cardiovascular medicine. The primary source of
      publications is PUBMED listings under Randomised Controlled Trials and Clinical
      Trials. The rjle of neural networks is introduced within the context of advances
      in medical decision support arising from parallel developments in statistics and
      artificial intelligence. This is followed by a survey of published Randomised
      Controlled Trials and Clinical Trials, leading to recommendations for good
      practice in the design and evaluation of neural networks for use in medical
      intervention.

PMID- 11958485
TI  - Equivariant nonstationary source separation.
AB  - Most of source separation methods focus on stationary sources, so higher-order
      statistics is necessary for successful separation, unless sources are temporally
      correlated. For nonstationary sources, however, it was shown [Neural Networks 8
      (1995) 411] that source separation could be achieved by second-order
      decorrelation. In this paper, we consider the cost function proposed by Matsuoka
      et al. [Neural Networks 8 (1995) 411] and derive natural gradient learning
      algorithms for both fully connected recurrent network and feedforward network.
      Since our algorithms employ the natural gradient method, they possess the
      equivariant property and find a steepest descent direction unlike the algorithm
      [Neural Networks 8 (1995) 411]. We also show that our algorithms are always
      locally stable, regardless of probability distributions of nonstationary sources.

PMID- 11958486
TI  - Fractional Fourier transform pre-processing for neural networks and its
      application to object recognition.
AB  - This study investigates fractional Fourier transform pre-processing of input
      signals to neural networks. The fractional Fourier transform is a generalization
      of the ordinary Fourier transform with an order parameter a. Judicious choice of
      this parameter can lead to overall improvement of the neural network performance.
      As an illustrative example, we consider recognition and position estimation of
      different types of objects based on their sonar returns. Raw amplitude and time
      of-flight patterns acquired from a real sonar system are processed, demonstrating
      reduced error in both recognition and position estimation of objects.

PMID- 11958487
TI  - Comments for: Rivals, I., & Personnaz, L. (2000). Construction of confidence
      intervals for neural networks based on least squares estimation. Neural Networks,
      13, 463-484.

PMID- 11958488
TI  - Attention modulation of neural tuning through peak and base rate in correlated
      firing.
AB  - The present study investigates the influence of attention modulation on neural
      tuning functions under a Gaussian correlation structure. Recent experiments have
      shown that attention modulates the tuning curve via its height and base rate.
      Inspired by this experimental finding, we previously showed the effective size of
      attention modulation (i.e. the critical length) on the neural population that
      enhances encoding accuracy. The previous result, however, was obtained under the
      assumption of uncorrelated firing, i.e. stimulus-conditional independence of
      neural responses. A question still remains whether the above findings can be
      applied to correlated firing. It is important to investigate this issue partly
      because neural firings are usually correlated but even more so because common
      attentional inputs may cause correlated firings. The present study first provides
      the general framework of attention modulation in relation to an attended stimulus
      and an actual stimulus and then shows the existence of a critical length under a
      Gaussian correlation structure. In order to improve encoding accuracy, measured
      by the Fisher information, the height and the base rate should be increased when
      the attended stimulus is in the critical length from the peak of the tuning curve
      and decreased otherwise. Furthermore, we confirm that a similar nature of the
      critical length also holds even when the neural decoder uses an uncorrelated
      unfaithful model. Thus, the existence of the critical length seems to be a
      ubiquitous phenomenon in attention modulation, and so its implications are
      discussed.

PMID- 11958490
TI  - Space-filling curves and Kolmogorov superposition-based neural networks.
AB  - Kolmogorov superpositions and Hecht-Nielsen's neural network based on them are
      dimension reducing. This dimension reduction can be understood in terms of space
      filling curves that characterize Kolmogorov's functions, and the subject of this
      paper is the construction of such a curve. We construct a space-filling curve
      with Lebesgue measure 1 in the unit square, [0,1]2, with approximating curves
      lambda(k), k = 1,2,3,..., each with 10(2k) rational nodal-points whose order is
      determined for each k by the linear order of their image-points under a
      nomographic function y = alpha1psi(x1) + alpha2psi(x2) that is the basis of a
      computable version of the Kolmogorov superpositions in two dimensions. The
      function psi:[0,1] --> [0,1] is continuous and monotonic increasing, and alpha1,
      alpha2 are suitable constants. The curves lambda(k) are composed of families of
      disjoint closed squares of diminishing diameters and connecting joins of
      diminishing lengths as k --> infinity.

PMID- 11958489
TI  - Modeling inferior olive neuron dynamics.
AB  - A model for the study of the dynamic properties of inferior olive neuron is
      presented. The model, a dynamical system, comprises two autonomous components of
      minimal complexity that are capable of reproducing the large gamut of
      experimentally observed inferior olive neuron dynamics. The two autonomous parts
      are responsible for largely different aspects of the dynamic profile of the
      model. These include subthreshold oscillations and different modes (high and low
      threshold) of action potential generation.

PMID- 11958491
TI  - The Bifurcating Neuron Network 2: an analog associative memory.
AB  - The Bifurcating Neuron (BN), a chaotic integrate-and-fire neuron, is a model of a
      neuron augmented by coherent modulation from its environment. The BN is
      mathematically equivalent to the sine-circle map, and this equivalence
      relationship allowed us to apply the mathematics of one-dimensional maps to the
      design of a BN network. The study of the bifurcating diagram of the BN revealed
      that the BN, under a suitable condition, can function as an amplitude-to-phase
      converter. Also, being an integrate-and-fire neuron, it has an inherent
      capability to function as a coincidence detector. These two observations led us
      to the design of the BN Network 2 (BNN-2), a pulse-coupled neural network that
      exhibits associative memory of multiple analog patterns. In addition to the usual
      dynamical properties as an associative memory, the BNN-2 was shown to exhibit
      volume-holographic memory: it switches to different pages of its memory space as
      the frequency of the coherent modulation changes, meaning context-sensitive
      memory.

PMID- 11958492
TI  - Hybrid independent component analysis by adaptive LUT activation function
      neurons.
AB  - The aim of this paper is to present an efficient implementation of unsupervised
      adaptive-activation function neurons dedicated to one-dimensional probability
      density estimation, with application to independent component analysis. The
      proposed implementation is a computationally light improvement to adaptive pseudo
      polynomial neurons, recently presented in Fiori, S. (2000a). Blind signal
      processing by the adaptive activation function neurons. Neural Networks, 13(6),
      597-611, and is based upon the concept of 'look-up table' (LUT) neurons.

PMID- 11958493
TI  - A new approach to stability of neural networks with time-varying delays.
AB  - The stability of neural networks is a prerequisite for successful applications of
      the networks as either associative memories or optimization solvers. Because the
      integration and communication delays are ubiquitous, the stability of neural
      networks with delays has received extensive attention. However, the approach used
      in the previous investigation is mainly based on Liapunov's direct method. Since
      the construction of Liapunov function is very skilful, there is little
      compatibility among the existing results. In this paper, we develop a new
      approach to stability analysis of Hopfield-type neural networks with time-varying
      delays by defining two novel quantities of nonlinear function similar to the
      matrix norm and the matrix measure, respectively. With the new approach, we
      present sufficient conditions of the stability, which are either the
      generalization of those existing or new. The developed approach may be also
      applied for any general system with time delays rather than Hopfield-type neural
      networks.

PMID- 11958494
TI  - Testing for factor V Leiden in patients with pulmonary or venous thromboembolism:
      a cost-effectiveness analysis.
AB  - BACKGROUND: Survivors of venous thromboembolism who have the factor V Leiden
      mutation have an increased risk of recurrent venous thromboembolism (VTE), but
      the cost-effectiveness of testing for factor VLeiden has not been assessed.
      METHODS: We used a Markov state transition decision model to evaluate the cost
      effectiveness of factor V Leiden testing and treatment strategies in survivors of
      VTE using a societal perspective for costs, effectiveness-measured in quality
      adjusted life years, and incremental cost-effectiveness. Data sources included
      the English language literature using MEDLINE searches and bibliographies from
      selected articles. Cost estimates were derived from Medicare reimbursement and
      other sources. The analysis examined 3 hypothetical cohorts of 35-year-old women
      having suffered their 1st episode of VTE. Interventions included oral
      anticoagulant therapy for 6 months versus testing. Patients found to have the
      factor V Leiden mutation were then treated with either 3 years or lifelong oral
      anticoagulant therapy. RESULTS: Total costs for testing followed by 3 years of
      treatment were $9,676, whereas those for no testing were $10,392 and those for
      testing followed by lifelong therapy were $13,179. Testing followed by 3 years of
      treatment increased quality-adjusted life expectancy by roughly 0.15 years. In
      sensitivity analyses using a more plausible constant risk model of recurrent VTE,
      testing followed by lifelong anticoagulation was the favored strategy. However,
      the marginal cost-effectiveness ratio was highly dependent on the rate of
      recurrent VTE, the risk of major hemorrhage, prevalence of factor V Leiden,
      patient age, and the efficacy of anticoagulation therapy. CONCLUSIONS: Testing
      followed by lifelong anticoagulation is unlikely to be a cost-effective strategy
      in patient populations with a very low prevalence of factor V Leiden; for those
      with a lower risk for recurrent VTE, such as patients with a clear precipitant;
      or for patients with risk factors for bleeding while receiving anticoagulant
      therapy. The only patients for whom testing followed by lifelong anticoagulant
      therapy may be a reasonable strategy are those with no obvious precipitant for
      VTE (i.e., idiopathic VTE) who are at low risk for bleeding complications from
      oral anticoagulant therapy. These results highlight the need for further clinical
      investigation and the development of multivariable models predicting the risk of
      recurrent VTE based on factor V Leiden status, idiopathic versus precipitated
      VTE, treatment, and the coinheritance of other common thrombophilias, such as the
      prothrombin gene mutation.

PMID- 11958495
TI  - Randomized controlled trial of a patient decision aid for colorectal cancer
      screening.
AB  - PURPOSE: To conduct a pilot test of a decision aid designed to help patients
      choose among currently recommended colorectal cancer screening programs. METHODS:
      Randomized controlled trial comparing a patient decision aid based on
      multicriteria decision-making theory with a simple educational intervention.
      PATIENT POPULATION: 96 patients at average risk for colorectal cancer seen in an
      Internal Medicine practice in Rochester, New York. OUTCOME MEASURES: The two
      primary outcome measures were patient decision process and the decision outcome.
      Patient decision process was assessed using the decisional conflict scale.
      Decision outcome was defined as the proportion of colorectal cancer screening
      plans carried out. RESULTS: After controlling for the effects of the physicians
      in a factorial analysis of variance, patients who used the decision aid had lower
      decisional conflict regarding colorectal cancer screening decisions (F ratio
      6.47, P = 0.01) due to increased knowledge, better clarity of values, and higher
      ratings of the quality of the decisions they made. There was no difference
      between the groups in decision outcomes: 52% of patients in the control group and
      49% in the experimental group completed planned screening tests (P = 1.0).
      CONCLUSIONS: In a pilot study, a multicriteria-based patient decision aid for
      colorectal cancer screening improved patients' decision-making processes but had
      no effect on the implementation of screening plans.

PMID- 11958496
TI  - Judgment analysis of prioritization decisions within a dialysis program in one
      United Kingdom region.
AB  - BACKGROUND: Some previous research on rationed clinical services has confused the
      conceptual differences underpinning prioritization decisions on the one hand and
      assessments of individual need on the other. The balance of the clinical and
      nonclinical drivers of these decisions can be different. Our objective was to
      study the basis and extent of variation among nephrologists in one NHS region in
      their views concerning prioritization for dialysis. DESIGN AND METHODS: In a
      clinical judgment analysis, multiple regression analysis was used to express the
      impact of clinical and nonclinical cues on nephrologists' decisions to offer
      dialysis and attribute priority to 50 "paper patients." Cues were selected for
      the decision-making models using stepwise (backward) elimination of variables.
      Further "policy" models for priority were derived by forcing in the doctors'
      views about the capacity of dialysis to extend life expectancy or improve its
      quality. RESULTS: Comparison of "propensity to offer" and "prioritization"
      decision models showed a modest degree of correspondence. Among the nonrenal
      cues, the patient's mental state made the single greatest contribution to the
      priority decision models (mean contribution to R2 = 12.1, with temporary or
      permanent confusional states in patients changing the priority [1-50] by an
      average of 15 rank places). Although patient age significantly influenced the
      decision models of half of the doctors, the beta-coefficients were very modest,
      suggesting a change in rank order of no more than one place. There was a
      significant improvement in the overall explained variance (R2) of the models when
      varying perceptions of the capacity of dialysis to improve the quality or extend
      the duration of the patient's life were forced into the model. Although, in
      general, temporary or permanent confusion in the patient down-graded the priority
      for dialysis by between 10 and 20 places, this tendency was largely unchanged
      when the doctors' perceptions of benefit were forced into the priority model.
      Among renal cues, the presence of uremic symptoms had the greatest impact on
      priority (mean contribution to R2 = 49.1, mean beta-coefficient -17.1), whereas
      the presence of other comorbid disease had relatively little effect. CONCLUSIONS:
      When forced to rank patients, the nonrenal factor that had the most significant
      bearing on perceived priority for dialysis was the patient's mental state.
      However, the impact of the patient's mental state on priority did not appear to
      be driven by its influence on the doctors' perceptions of how dialysis might
      improve quality of life.

PMID- 11958497
TI  - Bayesian extensions of the Tobit model for analyzing measures of health status.
AB  - Self-reported health status is often measured using utility indices that provide
      a score intended to summarize an individual's health. Measurements of health
      status can be subject to a ceiling effect. Frequently, researchers want to
      examine relationships between determinants of health and measures of health
      status. In this article, Bayesian extensions of the classical Tobit model are
      used to study the relationship between health status and predictors of health.
      The author examined models where the conditional distribution of health status
      was either normal or lognormal, and allowed for both homoscedasticity and
      heteroscedasticity. Bayes factors were then used to compare the evidence for a
      given model against that for a competing model. The author found very strong
      evidence that the distribution of the Health Utilities Index, conditional on age,
      gender, income adequacy, and number of chronic conditions, was normal with
      nonuniform variance, compared to the competing models.

PMID- 11958498
TI  - A comparison of Bayesian methods for profiling hospital performance.
AB  - There is a growing interest in the use of Bayesian methods for profiling
      institutional performance. In the literature, several studies have compared
      different frequentist methods for classifying hospitals as performance outliers.
      The purpose of this study was to compare 4 different Bayesian methods for
      classifying hospitals as outcomes outliers, using 30-day hospital-level mortality
      rates for a cohort of acute myocardial infarction patients as a test case. The
      1st Bayesian method involved determining the probability that a hospital's
      mortality rare for an average patient exceeded a specified threshold. The 2nd
      method involved ranking hospitals according to their mortality rate for an
      average patient. The 3rd method involved determining the probability that a
      hospital's standardized mortality ratio exceeded a specified threshold. The 4th
      method involved ranking hospitals according to their standardized mortality
      ratio. In most of the scenarios examined, there was only marginal agreement
      between the different methods. In only 4 of 19 comparisons, was there good
      agreement between the different methods (0.40 < or = kappa < or = 0.75). Methods
      based on ranking institutions were relatively insensitive to differences between
      hospitals. These inconsistencies raise questions about the choice of methods for
      classifying hospital performance, and they suggest a need for urgent research
      into which methods are best able to discriminate between institutions and which
      are most meaningful to decision makers.

PMID- 11958499
TI  - A note on the estimation of confidence intervals for cost-effectiveness when
      costs and effects are censored.
AB  - BACKGROUND: The relation between methodological advances in estimation of
      confidence intervals (CIs) for incremental cost-effectiveness ratios (ICER) and
      estimation of cost effectiveness in the presence of censoring has not been
      explored. The authors address the joint problem of estimating ICER precision in
      the presence of censoring. METHODS: Using patient-level data (n = 168) on cost
      and survival from a published placebo-controlled trial, the authors compared 2
      methods of measuring uncertainty with censored data: 1) Bootstrap with censor
      adjustment (BCA); 2) Fieller's method with censor adjustment (FCA). The authors
      estimate the FCA over all possible values for the correlation (rho) between costs
      and effects (range = -1 to + 1) and also examine the use of the correlation
      between cases without censoring adjustment (i.e., simple time-on-study) for costs
      and effects as an approximation for rho. RESULTS: Using time-on-study, which
      considers all censored observations as responders (deaths), yields 0.64 life
      years gained at an additional cost of 87.9 for a cost per life-year of 137 (95%
      CI by bootstrap -5.9 to 392). Censoring adjustment corrects for the bias in the
      time-on-study approach and reduces the cost per life-year estimate to 132
      (=72/0.54). Confidence intervals with censor adjustment were approximately 40%
      wider than the base-case without adjustment. Using the Fieller method with an
      approximation of rho based on the uncensored cost and effect correlation provides
      a 95% CI of (-48 to 529), which is very close to the BCA interval of (-52 to
      504). CONCLUSIONS: Adjustment for censoring is necessary in cost-effectiveness
      studies to obtain unbiased estimates of ICER with appropriate uncertainty limits.
      In this study, BCA and FCA methods, the latter with approximated covariance, are
      simple to compute and give similar confidence intervals.

PMID- 11958500
TI  - Looking back and looking forward: viewed through the eyes of George Torrance.

PMID- 11958501
TI  - Presidential address: proactive decision making.

PMID- 11958502
TI  - Law and ethics.

PMID- 11958503
TI  - Peripheral arterial occlusive disease: prognostic value of signs, symptoms, and
      the ankle-brachial pressure index.
AB  - OBJECTIVES: To determine whether different levels of the ankle-brachial pressure
      index (ABPI) are associated with an increased risk for progressive limb ischemia,
      nonfatal and fatal cardiovascular events. To investigate the prognostic value of
      signs and symptoms associated with peripheral arterial occlusive disease (PAOD).
      DESIGN: Prospective follow-up study. SETTING: Eighteen general practice centers
      in the Netherlands. PARTICIPANTS: Three thousand six hundred forty-nine
      participants (53% female) with a mean age of 59 years (range: 40-78 years). MAIN
      OUTCOME MEASURES: Progressive limb ischemia, cardiovascular morbidity and
      mortality. RESULTS: At baseline, 458 participants had PAOD, defined as an ABPI <
      0.95. Among these, 148 (32.2%) had an ABPI < 0.70. Cox proportional hazards
      models showed that after a mean follow-up period of 7.2 years, PAOD patients with
      an ABPI < 0.70 were at higher risk for cardiovascular death, compared with
      participants with a moderately reduced ABPI (< 0.95 - > or = 0.70): HR 2.3 versus
      1.2. Older age, complaints of intermittent claudication, abnormal pedal pulses,
      elevated blood pressure, and coexisting cardiovascular disease at baseline were
      also significant independent prognostic factors for one or more of the adverse
      outcome events in these patients. CONCLUSION: The ABPI is inversely associated
      with cardiovascular mortality in PAOD patients. A low ABPI is an independent
      predictor for cardiovascular mortality in PAOD patients.

PMID- 11958504
TI  - Does catheter type effect pregnancy rate in intrauterine insemination cycles?
AB  - PURPOSE: To determine if a soft insemination catheter increases pregnancy rates.
      METHODS: Seven hundred forty-seven consecutive intrauterine insemination (IUI)
      cycles in 364 women in a reproductive endocrinology office between October 1998
      and March 2000. Patients with even birth years were inseminated with the Tomcat
      catheter, and those with odd birth year with the Wallace IUI catheter. Clinical
      pregnancy rates were compared. RESULTS: The Wallace catheter group included 180
      women for 372 cycles and an overall pregnancy rate of 16.4%. The Tomcat catheter
      group included 184 women for 375 cycles and an overall pregnancy rate of 18.1%.
      This difference is not statistically significant (P = 0.61). Potential
      confounders were accounted for. CONCLUSIONS: When comparing the softer Wallace
      catheter to the less pliable Tomcat catheter during IUI cycles, there was no
      significant difference in pregnancy rate when using a standard gentle technique
      that includes not touching the top of the fundus with the catheter.

PMID- 11958505
TI  - Intracytoplasmic sperm injection with testicular spermatozoa in men with
      azoospermia.
AB  - PURPOSE: The aim of the study was to gain an insight into the optimal management
      of the infertile couple with the husband suffering from azoospermia. METHODS: One
      hundred and forty-two intracytoplasmic sperm injection (ICSI) cycles performed
      with testicular extracted spermatozoa were retrospectively analysed. The
      following factors were investigated for their possible influence on
      fertilization, cleavage, damage, pregnancy, and ongoing pregnancy rates: the use
      of fresh, cryopreserved, and preincubated (24 h) spermatozoa and the etiology of
      the husbands' azoospermia (obstructive and nonobstructive). All microinjections
      were performed with apparently normal spermatozoa--a head with a tail of normal
      length. In 116 cycles at least two embryos were available for transfer. RESULTS:
      The overall fertilization, clinical pregnancy, and ongoing pregnancy rates
      obtained for the 116 cycles were 65.0, 30.2, and 22.4% respectively. Similar
      outcomes were obtained for cycles using fresh testicular and cryopreserved
      testicular spermatozoa. Similarly, no significant differences were obtained
      between the cycles using spermatozoa from obstructive or nonobstructive
      azoospermic patients. An increase in motility after a 24-h preincubation was
      observed, and although this group was relatively small (n = 17), a significant
      improvement in fertilization (73.7%) and pregnancy (53.9%) rate was obtained when
      the testicular sample was preincubated for 24 h. This improvement prevailed in
      the obstructive azoospermic group, but was less pronounced in nonobstructive
      patients. CONCLUSIONS: This study shows that the outcome of fresh and frozen
      thawed testicular spermatozoa in ICSI is comparable, obstructive and
      nonobstructive etiologies perform the same, and that preincubation of testicular
      spermatozoa results in increased fertilization and pregnancy rates. All
      testicular biopsies are therefore performed the day before oocyte retrieval,
      superfluous spermatozoa cryopreserved, and the remaining testicular homogenate
      preincubated for the 24 h prior to oocyte retrieval. With this regime, most
      azoospermic patients are treated successfully, irrespective of the use of fresh
      or frozen-thawed spermatozoa from obstructive or nonobstructive cases.

PMID- 11958506
TI  - The mitochondrial DNA mutation (deltamtDNA5286) in human oocytes: correlation
      with age and IVF outcome.
AB  - PURPOSE: To evaluate the correlation between the presence of a newly described
      mitochondrial DNA (mtDNA) mutation (deltamtDNA5286), patients' age, and in vitro
      fertilization (IVF) outcomes. METHODS: The presence of deltamtDNA5286 was
      analyzed by nested-primer PCR in 224 unfertilized oocytes of 81 women undergoing
      IVF for various reasons. Age, number of oocytes retrieved, fertilization and
      embryo cleavage, number of embryos transferred, and pregnancy rates were compared
      between patients with and without a mtDNA mutation in their oocytes. RESULTS: The
      23 patients in which deltamtDNA5286 was detected in at least one oocyte were
      significantly younger than the other 58 with no mutations (30.9 years vs. 33.8
      years, respectively, P = 0.03), and had a significantly lower fertilization rate
      (28.9% vs. 42.1%, respectively, P = 0.01). No other outcome variable was
      significantly different between the two groups. CONCLUSION(S): The mtDNA mutation
      deltamtDNA5286 may serve as a marker of decreased oocyte quality in IVF.

PMID- 11958507
TI  - Cytogenetic analysis of embryos generated from in vitro matured mouse oocytes
      reveals an increase in micronuclei due to chromosome fragmentation.
AB  - PURPOSE: (i) To determine the prevalence of micronuclei in the cytoplasm of
      embryos generated from in vitro matured oocytes. (ii) Assess whether micronuclei
      presence are the result of chromosome fragmentation or the loss of whole
      chromosomes. METHODS: In vitro fertilization was performed on mature oocytes
      generated from superovulated mice (control) and in vitro matured mouse oocytes.
      Fertilized oocytes were cultured to the two-cell stage and fixed to slides.
      Micronuclei assessment was performed after staining with Giemsa. Centromere
      assessment was made using immunofluorescent staining (CREST) of the centromeric
      kinetochores. RESULTS: Micronuclei were observed in 2% (4/197) of control two
      cell embryos and 36.2% (46/127) of two-cell embryos generated from in vitro
      matured oocytes (P < 0.02). Centromeres were not detected in micronuclei from
      either group. CONCLUSIONS: A significant increase in micronuclei was observed in
      embryos generated from in vitro matured oocytes. The lack of
      accompanyingcentromeres would suggest the micronuclei are the result of
      chromosome fragmentation.

PMID- 11958508
TI  - Embryonic platelet-activating factor: temporal expression of the ligand and
      receptor.
AB  - PURPOSE: Preimplantation embryos synthesize platelet-activating factor (PAF) and
      this embryo-derived PAF is required for development. PAF's signal transduction is
      receptor-mediated and PAF-receptor mRNA is present in early embryos. The study
      objective was to determine the relationship between PAF production and PAF
      receptor mRNA expression levels in mouse preimplantation embryos. METHODS: Embryo
      derived PAF levels were determined by radioimmunoassay. Embryonic PAF-receptor
      mRNA levels were determined by semiquantitated reverse transcription-polymerase
      chain reaction. RESULTS: Embryonic-PAF increased as time progressed at a
      relatively constant rate (1.4-1.9 x) except between the eight- and morula-cell
      stages where levels increased sevenfold. Embryonic PAF-receptor expression was
      highest at the two-cell stage and decreased steadily until the morula stage
      before increasing again. Regression analysis of embryo-derived PAF on PAF
      receptor expression does not demonstrate a significant relationship. CONCLUSIONS:
      PAF-receptor expression (mRNA) levels decrease, while embryo-derived PAF levels
      decrease, as the preimplantation embryo develops. Embryonic-PAF and PAF-receptor
      mRNA expression do not appear related. Therefore, embryonic-PAF does not appear
      to regulate expression of its own receptor in vitro. The data provide a clue to
      the complicated cell signaling system involving PAF production and receptor
      expression that may help our understanding of developmental events.

PMID- 11958510
TI  - Intracytoplasmic injection using spermatids and subsequent pregnancies: round
      versus elongated spermatids.
AB  - The purpose of this clinical trial study was to report the outcome of
      intracytoplasmic injection of round (RS) and elongated (ES) spermatids retrieved
      from the testis of nonobstructive men. Seven and three cycles using RS and ES
      injections were performed, respectively. Only one cycle utilizing the late stage
      of ES (Sd2) resulted in an on-going pregnancy. The remarkable low success rate
      following RS microinjection was established in this study.

PMID- 11958509
TI  - In vivo gene transfer of leukemia inhibitory factor (LIF) into mouse endometrium.
AB  - PURPOSE: Leukemia inhibitory factor (LIF) is important for embryogenesis and
      implantation. We aimed to transfect LIF gene into the mouse endometrium.
      MATERIALS AND METHODS: Expression plasmids carried LIF and luciferase genes for
      transfer. After superovulation, 100 ICR mice were mated with vasectomized mice.
      Then LIF-liposome (Group 1) and luciferase-liposome complexes (Group 2) were
      injected into their uterine lumen (Day 0). Endometrial LIF and luciferase
      expressions were detected by reverse transcription-polymerase chain reaction on
      Days 0-4 post gene transfer. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was
      used as an internal control to normalize the gene transfection. RESULTS: LIF mRNA
      and luciferase activities reached the peak expression on Day 3. In Group 1, the
      ratios of LIF/GADPH on Days 1-4 were 0.414, 1.096, 1.162, and 0.782. In Group 2.
      LIF/GADPH on Days 1-4 were 0.24, 0.22, 0.35, and 0.32. CONCLUSIONS: Mouse
      endometrium could be effectively transfected with liposome-DNA mixtures.
      Endometrial LIF transfer via liposome may be effective in human.

PMID- 11958511
TI  - Inadvertent superovulation and intrauterine insemination during pregnancy: a
      lesson from an ectopic gestation.
AB  - It is believed that follicular development and ovulation is suppressed during the
      early period of gestation in humans. In this report, we describe a patient who
      underwent ovarian hyperstimulation following a "presumed" menstrual bleeding. The
      case illustrates that the ovaries during early pregnancy seem to respond normally
      to exogenous gonadotrophin stimulation. Despite ongoing pregnancy, the high
      plasma concentrations of gonadotrophins have rescued pituitary and ovarian
      insensitivity. Normal follicular development and even ovulation are allowed to
      occur. Moreover, it is mandatory to preclude pregnancy before commencing
      superovulation and assisted reproductive technology.

PMID- 11958512
TI  - Retroperitoneal subpancreatic ectopic pregnancy following in vitro fertilization
      in a patient with previous bilateral salpingectomy: how did it get there?
AB  - An unusual case of retroperitoneal ectopic pregnancy is reported. The patient, a
      34 year old nulligravida, underwent IVF/ET following bilateral salpingectomy. A
      small, degenerating, intrauterine gestational sac suggested failing intrauterine
      pregnancy. There was no intraperitoneal free fluid. On Day 41 after ET, the
      patient was hospitalized because of acute epigastric pains. A pseudocyst of the
      head of pancreas was demonstrated by CT scan. A day later, exploratory
      laparotomy, because of a precipitous drop in the hemoglobin, revealed a massive
      retroperitoneal hematoma and an embryo in the gestational sac attached to the
      head of pancreas and major blood vessels. The patient did well following surgery.
      The mechanisms of retroperitoneal embryo migration are discussed and literature
      is reviewed.

PMID- 11958513
TI  - Severe hypertriglyceridemia and pancreatitis following hormone replacement prior
      to cryothaw transfer.
AB  - PURPOSE: A case of acute pancreatitis with severe hypertriglyceridemia occurred
      following use of intramuscular estradiol valerate during endometrial preparation
      for cryopreserved embryos. METHODS: A 30-year-old woman with primary infertility
      and a past history of well-controlled hypothyroidism, underwent endometrial
      development with intramuscular estradiol valerate in preparation for the transfer
      of cryopreservred embryos. RESULTS: Initial hospitalization, discontinuation of
      all estrogens, aggressive intravenous fluid hydration, and initiation of low-fat
      diet with additional gemfibrozil treatment resulted in complete resolution of all
      symptoms related to the pancreatitis including the hyperlipidemia. A subsequent
      cryothaw cycle using oral estradiol resulted in a viable pregnancy with only mild
      increases in the patient's triglyceride and cholesterol levels noted throughout
      her 38-week gestation. CONCLUSION(S): Estradiol valerate, a commonly used form of
      estrogen for endometrial preparation during cryothaw cycles, may cause severe
      hypertriglyceridemia and acute pancreatitis in certain predisposed individuals.
      Oral and transdermal estrogens should be the preferred method of endometrial
      preparation in patients at high risk for lipid metabolism disorders, such as
      patients with polycystic ovarian syndrome and familial hypertriglyceridemia.
      These estrogens are more rapidly metabolized and have a shorter half life
      compared to that of estradiol valerate.

PMID- 11958514
TI  - Sarin causes altered time course of mRNA expression of alpha tubulin in the
      central nervous system of rats.
AB  - Sarin induced neurotoxicity is suspected to be one of the key factors responsible
      for Gulf-war syndrome. We studied the effect of a single (50 microg/kg/i.m) dose
      of sarin (0.5 x LD50) on the mRNA expression of alpha tubulin in the central
      nervous system (CNS) of rats which were sacrificed at different time points i.e.
      1 and 2 hrs, as well as, 1, 3 and 7 days post-treatment. Northern data collected
      from CNS regions indicate differential, spatial, and temporal regulation of alpha
      tubulin mRNA levels. Immediate induction and persistence of alpha tubulin
      transcripts in sarin-treated CNS suggest that sarin-induced neurotoxicity is in
      part mediated by the altered expression of cytoskeletal genes which may be
      regulated at multiple levels.

PMID- 11958515
TI  - Early differential elevation and persistence of phosphorylated cAMP-response
      element binding protein (p-CREB) in the central nervous system of hens treated
      with diisopropyl phosphorofluoridate, an OPIDN-causing compound.
AB  - Diisopropyl phosphorofluoridate (DFP) produces organophosphorus-ester-induced
      delayed neurotoxicity in sensitive species. We studied the effect of single dose
      of DFP on the expression of phosphorylated cAMP-response element binding protein
      (p-CREB), which is a well known transcription factor involved in several pathways
      mediating different types of external stimuli. The hens were perfused with
      neutral buffered formalin at different time points, i.e., 0.5, 1.0, and 2.0 hrs,
      as well as 1, 2, 5, and 20 days after dosing. The central nervous system regions
      of the whole brain were dissected and 7-micron sections were stained for either p
      CREB immunopositivity or with hematoxylin and eosin. Results indicated an early
      differential increase of p-CREB immunopositivity in susceptible regions such as
      cerebellum, brainstem, and midbrain within 2 hrs. These induced levels persisted
      upto 5 days in these tissues, although the time course of p-CREB immunopositivity
      was distinctly different for each region. In the cerebellum induction of p-CREB
      was seen in the granular layer where both the granulocytes and the glial cells
      showed induction. Increased immunopositivity for p-CREB in the Purkinje cells and
      in some basket cells of the molecular layer was noticed over time, but the
      induction was not as great as in the granular layer. Of all the tissues
      cerebellum showed the strongest intensity of immunopositivity of the cells as
      well as the highest (absolute) number of pCREB-positive cells. The brainstem
      showed a similar fluctuating pattern like the cerebellum with the highest
      percentage increase of the immunoreactive cells at 5 days preceded by the lowest
      dip in immunopositivity at 2 days. In the midbrain, there was a time-dependent
      increase in the immunopositivity from 0.5 hr onwards until reaching control
      levels at 20 days. Immunopositivity was also noted in portions of the spina
      medularis and spina oblongata. The cerebrum (non-susceptible tissue) of DFP
      treated hens did not show much deviation from the controls. The endothelial cells
      of the susceptible regions showed induction at early time points, in contrast to
      the absence of induction in cerebrum. Spatial and temporal differences in the
      immunopositivity pattern indicate probable involvement of CREB-independent
      pathways also. Overall, the complex induction pattern of p-CREB, along with our
      earlier observations of the early induction of c-fos, c-jun and Protein Kinase A
      (PKA) as well as the induction of Calcium2+/Calmodulin dependent Protein Kinase
      II (CaM kinase II) at later periods, strongly suggest an activator role of CREB
      mediated pathways that may lead to the clinical development of delayed
      neurotoxicity.

PMID- 11958516
TI  - Subunit composition and function of GABAA receptors of rat spermatozoa.
AB  - GABA triggers mammalian sperm acrosome reaction (AR). Here, evidence is
      presented, showing that rat spermatozoa contain GABAA receptors, composed of
      alpha5, beta1 and beta3 subunits. The effects of GABAA receptor agonist and
      antagonist on the induction of AR in rat spermatozoa were assessed using the
      chlortetracycline assay. Muscimol, a GABAA receptor agonist, triggered AR;
      whereas bicuculline, a GABAA receptor antagonist and picrotoxin, a GABAA
      receptor/Cl- channel blocker, inhibited the ability of GABA or progesterone to
      induce AR. In conclusion, GABAA receptors appear to mediate the action of
      progesterone in inducing AR in rat spermatozoa.

PMID- 11958517
TI  - Utilization of energy nutrients by cerebellar slices.
AB  - We performed an ontogenetic study about the utilization of glycine, glutamine,
      beta-hydroxybutyrate and glycerol as energy nutrients by rat cerebellum slices.
      Production of CO2 from glycerol and glutamine increased with the animals' age and
      glutamine was the most used nutrient for CO2 production. In adult age, glutamine
      oxidation to CO2 was 15 to 35 times higher than all other nutrients studied. CO2
      production from glycine decreased markedly with age and 10 day-old rats showed an
      oxidation 7.5 times higher than that of adult rats. At fetal age and at 10
      postnatal days, glycine oxidation to CO2 was only 2 times lower than glutamine
      oxidation to CO2. Lipid synthesis from beta-hydroxybutyrate was highest in adult
      rats. We did not observe any difference in the utilization of beta
      hydroxybutyrate between slices of cerebral cortex and cerebellum at the ages of
      10 days and adult. The main nutrients used for lipid synthesis were glycerol and
      beta-hydroxybutyrate.

PMID- 11958518
TI  - Tyrosine hydroxylase dephosphorylation by protein phosphatase 2A in bovine
      adrenal chromaffin cells.
AB  - This study was undertaken to characterise the protein phosphatases in bovine
      adrenal chromaffin cells acting on tyrosine hydroxylase. Cells were pre-labelled
      with 32Pi and permeabilized with digitonin. The extent of dephosphorylation of
      Ser-8, Ser-19, Ser-31 and Ser-40 on tyrosine hydroxylase was found to be 30%,
      38%, 37% and 71% respectively over 5 min. For Ser-19, Ser-31 and Ser-40 the
      dephosphorylation was entirely due to protein phosphatase 2A, as the
      dephosphorylation could be completely blocked by microcystin, but not by the
      protein phosphatase I inhibitory peptide. Permeabilization did not change the
      distribution of protein phosphatase 2A or tyrosine hydroxylase, or the activity
      of PP2A, from that occurring in intact cells. The dephosphorylation of Ser-8 was
      not altered by any inhibitor, suggesting the involvement of other protein
      phosphatases. The method developed here can be used to determine the protein
      phosphatases acting on substrates in conditions closely approximating those in
      situ, including the endogenous state of substrate phosphorylation and phosphatase
      location.

PMID- 11958519
TI  - Effect of R-(-)-deprenyl and harmaline on dopamine- and peroxynitrite-induced
      membrane permeability transition in brain mitochondria.
AB  - The present study examined the effect of MAO inhibitors, deprenyl and harmaline,
      on the membrane permeability transition in brain mitochondria. Deprenyl,
      harmaline, and antioxidant enzymes (SOD and catalase) attenuated alteration of
      the swelling, membrane potential, cytochrome c release, and Ca2+ transport in
      mitochondria treated with dopamine. In contrast, deprenyl and harmaline did not
      reduce the peroxynitrite-induced change in membrane permeability. Deprenyl and
      harmaline inhibited the decrease in thioredoxin reductase activity and the thiol
      oxidation in mitochondria treated with dopamine but did not decrease the effect
      of peroxynitrite. Deprenyl and harmaline significantly decreased the formation of
      melanin from dopamine. The results suggest that deprenyl and harmaline may
      protect brain mitochondria against the toxic action of dopamine oxidation by the
      maintenance of thioredoxin reductase activity, inhibition of thiol oxidation, and
      inhibition of dopamine oxidation product formation. In contrast, MAO inhibitors
      may not defend brain mitochondria against damaging action of peroxynitrite.

PMID- 11958520
TI  - T-588 enhances neurite outgrowth and choline acetyltransferase in cultured rat
      spinal ventral horn neurons.
AB  - T-588(R(-)-1-(benzo(b)thiophen-5yl)-2-[2(N,N-diethylamino)ethoxy]ethanol
      hydrochloride) is a novel compound which has been shown to exhibit a wide range
      of neurotrophic effects both in vivo and in vitro. This compound can slow the
      motor deterioration of wobbler mouse motor neuron disease. However, it is not
      known whether this compound has a trophic effect on spinal motor neurons. We have
      studied the effect of T-588 on neurite outgrowth and choline
      acetyltransferase(ChAT) activity in primary explant cultures of ventral spinal
      cord of fetal rats(VSCC). Cultures were treated with T-588 from day 1 to 1 week.
      T-588 treated VSCC, compared with control VSCC, had a significant neurite
      promoting effect at ranged between 10(-8) molar(M) and 10(-5) M, with 2.3 to 5.3
      fold increased over that of control VSCC. In T-588 treated VSCC, ChAT activity
      was increased 1.5 times over that of control at 10(-6), and 10(-5) M
      respectively. Our data showing T-588 has neurotrophic action on VSCC and suggests
      a potential use of T-588 in treating diseases that involve degeneration and death
      of spinal motor neurons, such as motor neuropathy and motor neuron disease.

PMID- 11958521
TI  - Dizocilpine inhibits amphetamine-induced formation of nitric oxide and
      amphetamine-induced release of amino acids and acetylcholine in the rat brain.
AB  - Glutamate receptor activation participates in mediation of neurotoxic effects in
      the striatum induced by the psychomotor stimulant amphetamine. The effects of the
      non-competitive NMDA receptor antagonist dizocilpine (MK-801) on amphetamine
      induced toxicity and formation of nitric oxide (NO) in both striatum and cortex
      and on induced transmitter release in the nucleus accumbens were investigated.
      Repeated, systemic application of amphetamine elevated striatal and cortical
      lipid peroxidation and NO production. Moreover, amphetamine caused an immediate
      release of acetylcholine and aspartate and a delayed release of GABA in the
      nucleus accumbens. Surprisingly, glutamate release was not affected. Dizocilpine
      abolished the amphetamine-induced lipid peroxidation and NO production in
      striatum and cortex and diminished the elevation of neurotransmitter release.
      These findings suggest that amphetamine evokes neurotoxic effects in both
      striatal and cortical brain areas that are prevented by inhibiting NMDA receptor
      activation. The amphetamine-induced acetylcholine, aspartate and GABA release in
      the nucleus accumbens is also mediated through NMDA receptor-dependent
      mechanisms. Interestingly, the enhanced aspartate release might contribute to
      NMDA receptor activation in the nucleus accumbens, while glutamate does not seem
      to mediate amphetamine-evoked transmitter release in this striatal brain area.

PMID- 11958523
TI  - Reducing ability of the striatum and cerebral cortex in rats following acute
      administration of risperidone or haloperidol: an estimation by in vivo electron
      paramagnetic resonance imaging.
AB  - In vivo temporal electron paramagnetic resonance (EPR) imaging of the blood-brain
      barrier-permeable nitroxide radical, 3-methoxycarbonyl-2,2,5,5
      tetramethylpyrrolidin-1-yloxy (PCAM), in the brain of rats was conducted
      following acute administration of risperidone (RSP) or haloperidol (HPD). The
      half-life of the signal intensity of PCAM was obtained from a selected area in
      the temporal EPR images. The half-lives in the striatum and cerebral cortex for
      the RSP- or HPD-treated rats were significantly longer than for the control rats
      (p < 0.01). This finding indicates that the reducing abilities of the striatum
      and cerebral cortex decreased in the rats to which either RSP or HPD had been
      acutely administrated because the half-life of PCAM in the selected region of the
      brain reflects its reducing ability.

PMID- 11958522
TI  - Iron deposition after transient forebrain ischemia in rat brain.
AB  - In this study, we investigated the iron deposition in the cerebral cortex,
      hippocampus CA1 area and corpus striatum pars dorsolateralis in a rat model of
      cerebral ischemia. Forebrain ischemia was induced by four-vessel occlusion for 20
      min. Using iron histochemistry, regional changes were examined from 1 to 8 weeks
      of postischemic recirculation. Neuronal death was demonstrated in pyramidal cells
      of the hippocampal CA1 area and in the dorsolateral part of the corpus striatum,
      which are known as areas most vulnerable to ischemia. Iron deposition in
      hippocampal CA1 area was coupled to delayed pyramidal cell death. Perl's reaction
      with DAB intensification revealed of the 1 week iron deposits in the CA1 area,
      which gradually increased and formed clusters by 8 weeks. In the corpus striatum,
      strong iron staining was observed in injured cellular layer pars dorsolateralis 1
      week after recirculation. Granular iron was deposited in the cytoplasm of
      pyramidal cells in layers III and V of the frontal cortex after 2 weeks of
      recirculation. In contrast to the hippocampus and striatum, the cerebral cortex
      did not develop severe neuronal cell death and atrophy immediately after the
      ischemic insult, which suggest that the neuronal cell death in the cerebral
      cortex occurs extremely late.

PMID- 11958524
TI  - Diabetes-related changes in rat cerebral occludin and zonula occludens-1 (ZO-1)
      expression.
AB  - The endothelial or epithelial tight junctions create a barrier to diffusion of
      solutes. Since experimental diabetes mellitus is associated with considerable
      alterations in the blood-brain barrier (BBB), it is possible that specific tight
      junction proteins may be altered in diabetes. To test this hypothesis, Western
      and Northern blot analysis were carried out to measure the steady-state level of
      occludin and zonula occludens-one (ZO-1) proteins and mRNA levels in cerebral
      tissue of streptozotocin-induced diabetic rats and the results were compared to
      insulin treated diabetic rats and vehicle injected control rats. The cerebral
      occludin content in diabetic rats (115.4 +/- 18.6 arbitrary units) was
      significantly reduced compared to insulin-treated diabetic rats (649.1 +/- 141.2)
      or control rats (552.9 +/- 82.9), p < 0.001. The ZO-1 content of cerebral tissue
      from diabetic rats (1,240.6 +/- 199.7 arbitrary units) was not significantly
      altered compared to controls (1,310.8 +/- 256.9). The cerebral occludin mRNA
      content relative to G3PDH mRNA was 1.35 +/- 0.07 and 1.34 +/- 0.19 in control and
      diabetic rats respectively. The cerebral ZO-1 mRNA content relative to G3PDH mRNA
      in diabetic and control rats was 1.135 +/- 0.123 and 0.956 +/- 0.038
      respectively. These differences did not achieve statistical significance. It is
      concluded that diabetes alters the molecular anatomy of the tight junctions in
      cerebral tissue by altering the content of select structural proteins.

PMID- 11958525
TI  - Receptors in the ventral tegmental area mediating nicotine-induced dopamine
      release in the nucleus accumbens.
AB  - Nicotine or cocaine, when administered intravenously, induces an increase of
      extracellular dopamine in the nucleus accumbens. The nicotine-mediated increase
      was shown to occur at least in part through increase of the activity of dopamine
      neurons in the ventral tegmental area. As part of our continuing studies of the
      mechanisms of nicotine effects in the brain, in particular, effects on reward and
      cognitive mechanisms, in the present study we examined the role of various
      receptors in the ventral tegmental area in nicotine and cocaine reward. We
      assayed inhibition of the increase of dopamine in the nucleus accumbens induced
      by intravenous nicotine or cocaine administration by antagonists administered
      into the ventral tegmental area. Nicotine-induced increase of accumbal dopamine
      release was inhibited by intrategmental nicotinic (mecamylamine), muscarinic
      (atropine), dopaminergic (D1: SCH 23390, D2: eticlopride), and NMDA glutamatergic
      (MK 801) and GABAB (saclofen) antagonists, but not by AMPA-kainate (CNQX,
      GYKI52466) antagonists under our experimental circumstances. The intravenous
      cocaine-induced increase of dopamine in the nucleus accumbens was inhibited by
      muscarinic (atropine), dopamine 2 (eticlopride), and GABAB (saclofen) antagonists
      but not by antagonists to nicotinic (mecamylamine), dopamine D1 (SCH 23390),
      glutamate (MK 801), or AMPA-kainate (CNQX, GYKI52466) receptors. Antagonists
      administered in the ventral tegmental area in the present study had somewhat
      different effects when they were previously administered intravenously. When
      administered intravenously atropine did not inhibit cocaine effects. The
      inhibition by atropine may be indirect, since this compound, when administered
      intrategmentally, decreased basal dopamine levels in the accumbens. The findings
      indicate that a number of receptors in the ventral tegmental area mediate
      nicotine-induced dopamine changes in the nucleus accumbens, a major component of
      the nicotine reward mechanism. Some, but not all, of these receptors in the
      ventral tegmental area also seem to participate in the reward mechanism of
      cocaine. The importance of local receptors in the ventral tegmental area was
      further indicated by the increase in accumbal dopamine levels after
      intrategmental administration of nicotine or also cocaine.

PMID- 11958526
TI  - Semicarbazide-sensitive amine oxidase (SSAO) in the brain.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) is widely distributed in almost
      tissues. However, its presence in brain microvessels is still controversial. The
      affinity of SSAO towards benzylamine (Bz) is considerably higher than that of
      monoamine oxidase (MAO). SSAO plays a role in the toxicity of several
      environmental and endogenous amines. SSAO-mediated production of toxic aldehydes
      has been proposed to be related to pathophysiological conditions. The most potent
      of inhibition of SSAO in monkey brain was observed by tricyclic antidepressant
      drug imipramine, as compared to tetracyclic drug maprotiline or non-cyclic drug
      nomifensine. An endogenous SSAO modulator in rat brain cytosol after
      immobilization stress (IMMO) was found and that this inhibitor could be induced
      by IMMO. SSAO activity in rat brain might be regulated by the level of this
      inhibitor. Semicarbazide, a SSAO inhibitor, enhances the formation of .OH
      products of efflux/oxidation due to 1-methyl-4-phenylpyridinium ion (MPP+). The
      precise physiological functions of SSAO could play an important role in the
      control of energy balance in adipose tissue. SSAO could play an important role in
      the regulation of adipocyte homeostasis.

PMID- 11958527
TI  - Short- and long-term effects of p-ethynylphenylalanine on brain serotonin levels.
AB  - Changes in tissue and extracellular serotonin (5-HT) in raphe dorsalis, raphe
      medialis and in their main projections areas (hippocampus, striatum and frontal
      cortex) were investigated at short and long-term times after single injection (5
      mg/kg ip) of a novel tryptophan hydroxylase inhibitor, p-ethynylphenylalanine (p
      EPA). The 5-HT tissue concentration decreased significantly in raphe nuclei, 30
      min post-injection and for 4 days, whereas it decreased from 24 hours post
      injection in the 5-HT projections. Normal 5-HT levels reappeared after 12 days
      post-injection in all areas. Moreover, in the projection areas, the extracellular
      5-HT levels decreased rapidly, 90, 40 and 30 min after p-EPA injection, in
      hippocampus, striatum and frontal cortex, respectively. Decreased accumulation of
      5-hydroxytryptophan (5-HTP) under NSD-101 perfusion in the serotoninergic
      projections after p-EPA injection, confirmed the direct inhibitory effect of the
      drug on the tryptophan hydroxylase activity. These results demonstrated that p
      EPA is a useful pharmacological tool which powerfully, acutely and irreversibly
      reduces the 5-HT levels.

PMID- 11958528
TI  - Effects of aging and amyloid-beta peptides on choline acetyltransferase activity
      in rat brain.
AB  - Choline acetyltransferase (ChAT, acetyl-CoA:choline O-acetyltransferase, EC
      2.3.1.6), involved in the learning and memory processes is responsible for the
      synthesis of acetylcholine. There are many discrepancies in literature concerning
      ChAT activity during brain aging and the role of amyloid beta peptides in
      modulation of this enzyme. The aim of the study was to investigate the mechanism
      of ChAT regulation and age-related alteration of ChAT activity in different parts
      of the brain. Moreover the effect of Abeta peptides on ChAT activity in adult and
      aged brain was investigated. The enzyme activity was determined in the brain
      cortex, hippocampus and striatum in adult (4-months-old), adult-aged (14-months
      old) and aged (24-months-old) animals. The highest ChAT activity was observed in
      the striatum. We found that inhibitors of protein kinase C, A, G and phosphatase
      A2 have no effect on ChAT activity and that this enzyme is not dependent on
      calcium ions. About 70% of the total ChAT activity is present in the cytosol.
      Arachidonic acid significantly inhibited cytosolic form of this enzyme. In the
      brain cortex and striatum from aged brain ChAT activity is inhibited by 50% and
      37%, respectively. The aggregated form of Abeta 25-35 decreased significantly
      ChAT activity only in the aged striatum and exerted inhibitory effect on this
      enzyme in adult, however, statistically insignificant. ChAT activity in the
      striatum was diminished after exposure to 1 mM H2O2. The results from our study
      indicate that aging processes play a major role in inhibition of ChAT activity
      and that this enzyme in striatum is selectively sensitive for amyloid beta
      peptides.

PMID- 11958529
TI  - Exposure to ebselen changes glutamate uptake and release by rat brain
      synaptosomes.
AB  - We investigated effects of Ebselen, diphenyl diselenide (PhSe)2 and diphenyl
      ditelluride (PhTe)2 on [3H]glutamate uptake and release by brain synaptosomes.
      Ebselen after acute exposure inhibited K+-stimulated [3H]glutamate release by
      brain synaptosomes. (PhSe)2 and (PhTe)2 did not change [3H]glutamate release by
      brain synaptosomes. Ebselen, (PhSe)2 and (PhTe)2 had no significantly effects on
      [3H]glutamate uptake after acute exposure. In vitro, Ebselen (100 microM)
      inhibited [3H]glutamate release and uptake. (PhSe)2 had no significant effect,
      while (PhTe)2 (100 microM) inhibited [3H]glutamate uptake by brain synaptosomes.
      In vitro, (PhSe)2, (PhTe)2 and Ebselen caused a significant inhibition of
      [3H]glutamate uptake by brain synaptic vesicles in vitro. The results
      demonstrated that organochalcogenides have a rather complex effect on glutamate
      homeostasis depending on the compound and the schedule of exposition. We propose
      that the neuroprotective action of Ebselen can be related, in addition to its
      glutathione peroxidase-like and antilipoperoxidative activity, to a direct
      interaction with the glutamatergic system by reducing K+-evoked glutamate
      release.

PMID- 11958530
TI  - Ethanol alters glutamate but not adenosine uptake in rat astrocytes: evidence for
      protein kinase C involvement.
AB  - Glutamate is the primary excitatory neurotransmitter in brain. By stimulating
      neuronal activity, glutamate increases cellular energy utilization, enhances ATP
      hydrolysis and promotes the formation of adenosine. Adenosine has receptor
      mediated effects that reduce or oppose the excitatory effects of glutamate. As a
      possible mechanism for ethanol's ability to inhibit excitatory effects of
      glutamate and enhance inhibitory effects of adenosine, we tested the hypothesis
      that ethanol promotes [3H]glutamate uptake and inhibits [3H]adenosine uptake.
      Using primary cultures of rat astrocytes, we found that acute treatment with
      ethanol (50 mM, 30 min) inhibited [3H]glutamate uptake and reduced protein kinase
      C (PKC)-induced stimulation of [3H]glutamate uptake. Prolonged treatment (50 mM,
      3 day) with ethanol, however, increased both [3H]glutamate uptake and PKC
      activity. Contrary to other cell types, neither acute or chronic ethanol exposure
      affected [3H]adenosine uptake in astrocytes. These data indicate that in rat
      cortical astrocytes ethanol affects [3H]glutamate uptake but not [3H]adenosine
      uptake by affecting PKC modulation of transporter activity.

PMID- 11958531
TI  - Antioxidant properties of new chalcogenides against lipid peroxidation in rat
      brain.
AB  - Ebselen (2-phenyl- 1,2-benzisoselenazole-3 (2H)-one) is a seleno-organic compound
      with antioxidant properties, and anti-inflammatory actions. Recently, ebselen
      improved the outcome of acute ischemic stroke in humans. In the present study,
      the potential antioxidant capacity of organochalcogenide compounds diphenyl
      diselenide (PhSe)2, diphenyl ditelluride (PhTe)2, diphenyl disulfide (PhS)2, p-Cl
      diphenyl diselenide (pCl-PhSe)2, bis-[S-4-isopropyl 2-phenyl oxazoline]
      diselenide (AA-Se)2, bis-[S-4-isopropyl 2-phenyl oxazoline] ditelluride (AA-Te)2
      and bis-[S-4-isopropyl 2-phenyl oxazoline] disulfide (AA-S)2 was compared with
      that of ebselen (a classical antioxidant). Spontaneous and quinolinic acid (QA)-
      (2 mM) and sodium nitroprusside (SNP)- (5 microM)-induced thiobarbituric reactive
      species (TBARS) production by rat brain homogenates was determined
      colorimetrically. TBARS formation was reduced by ebselen, (PhSe)2, (PhTe)2, (AA
      Se)2, (AA-S)2 and (pCl- PhSe)2 to basal rates. The concentrations of these
      compounds needed to inhibit TBARS formation by 50% (IC50) are 1.71 microM, 3.73
      microM, 1.63 microM, 9.85 microM, >33.3 microM, 23.2 microM and 4.83 microM,
      respectively for QA. For TBARS production induced by SNP the IC50 was 2.02
      microM, 12.5 microM, 2.80 microM, >33.3 microM, 24.5 microM and 7.55 microM,
      respectively. The compounds (AA-Te)2 and (PhS)2 have no antioxidant activity and
      pro-oxidant activity, respectively. These results suggest that (AA-Se)2 and (AA
      S)2 can be considered as potential pharmaceutical antioxidant agents.

PMID- 11958532
TI  - A new hypothalamic polypeptide is a regulator of myelopoiesis.
AB  - The effect of hypothalamic proline-rich polypeptide (PRP) against Pseudomonas
      aeruginosa infection in BALB/c mice with leukopenia was investigated. Mice were
      treated with cyclophosphamide (CPA) and were then injected with PRP 24 h after
      CPA treatment. The lethal doses of P. aeruginosa were injected to mice when the
      number of peripheral blood leukocytes reached a nadir on day 5 after CPA
      administration. The administration of PRP significantly increased the survival of
      infected mice, and had a pronounced protective effect during the period of
      development of the infection. The number of bacteria in internal organs of PRP
      treated mice was significantly lower than that in control mice. In PRP-treated
      mice, the neutrophil levels in peripheral blood started to increase 7 days after
      CPA administration and were consistently higher, and they were more mature than
      those in controls. Our results may indicate the ability of PRP to stimulate
      recovery of myelopoiesis and enhance mature neutrophil function.

PMID- 11958533
TI  - PAF-stimulated protein tyrosine phosphorylation in hippocampus: involvement of NO
      synthase.
AB  - The effect of platelet-activating factor (PAF) on protein tyrosine
      phosphorylation was studied in rat hippocampal slices. PAF caused an increase in
      the tyrosine phosphorylation of two phosphoproteins, which we identified by
      immunoprecipitation assays as the focal adhesion kinase p125FAK and crk
      associated substrate p130Ca. The PAF effect was time- and dose-dependent. In
      addition, the involvement of PAF receptor was demonstrated by using PCA-4248, a
      specific receptor antagonist. When NO synthase was inhibited by NG-monomethyl-L
      arginine (L-NMA), PAF-stimulated protein tyrosine phosphorylation was inhibited.
      In conclusion, our results indicate that PAF increased the tyrosine
      phosphorylation of both p125FAK and p130Cas proteins by the production of NO in
      hippocampus, suggesting that PAF may play a role in the functioning of this
      cerebral area.

PMID- 11958534
TI  - Ginkgo biloba extracts EGb 761 and bilobalide increase NADH dehydrogenase mRNA
      level and mitochondrial respiratory control ratio in PC12 cells.
AB  - In the present study, we investigated the effect of Ginkgo biloba extract, EGb
      761, and one of its components, bilobalide, on gene expression of subunit 1 of
      mitochondrial NADH dehydrogenase (ND1) in PC12 cells. By Northern blot analysis
      we found a approximately 2-fold significant increase in NDI mRNA level, after 48
      and 72 h exposure to 100 microg/ml EGb 761 and to 10 microg/ml bilobalide. We
      also evaluated, by oxygraphy measurements, mitochondrial respiration during state
      3 and state 4. In cells treated with EGb 761 and bilobalide for 48 and 72 h,
      state 4 respiration was significantly decreased, and the respiratory control
      ratio was increased. These results provide evidence that EGb 761 and bilobalide
      exert their protective effects by up-regulating mitochondrial ND1 gene expression
      and by decreasing state 4 respiration, whose increase is thought to be
      responsible for oxidative damage.

PMID- 11958535
TI  - Uptake of mannose-terminal glucocerebrosidase in cultured human cholinergic and
      dopaminergic neuron cell lines.
AB  - Enzyme replacement therapy has been shown to be particularly effective for
      patients with type 1 (non-neuronopathic) Gaucher disease. However, intravenously
      administered glucocerebrosidase does not reverse or halt the progression of brain
      damage in patients with type 2 (acute neuronopathic) Gaucher disease. A previous
      investigation revealed that intracerebral infusion of mannose-terminal
      glucocerebrosidase was safe in experimental animals. The enzyme had a
      comparatively long half-life in the brain. It was transported by convection from
      the site of infusion along white matter fiber tracts to the cerebral cortex where
      it was endocytosed by neurons. In anticipation of intracerebral administration of
      mannose-terminal glucocerebrosidase to patients with type 2 Gaucher disease, it
      was important to learn the mechanism involved in its cellular uptake. We
      therefore compared the endocytosis of this enzyme by J774 macrophage cells with
      that in two human neuronal cell lines and a human astrocyte cell line. Mannose
      terminal glucocerebrosidase was taken up by cholinergic LA-N-2 cells, but to a
      much lower extent than by macrophages. Considerably less of the enzyme was
      endocytosed by dopaminergic SH-SY5Y cells. It was not taken up by NHA astrocytes.
      The findings provide encouragement for an exploration of intracerebral
      administration of glucocerebrosidase in patients with type 2 Gaucher disease.

PMID- 11958536
TI  - Chronic cerebral hypoperfusion induces striatal alterations due to the transient
      increase of NO production and the depression of glutathione content.
AB  - We examined the effects of chronic cerebral hypoperfusion on the endogenous
      oxidative stress-related indices, nitrite and nitrate (NOx) concentration,
      glutathione (GSH) content, superoxide dismutase and catalase activities, and
      thiobarbituric acid-reactive substances level in the rat striatum, to clarify the
      participation of oxidative stress in the chronic cerebral hypoperfusion-induced
      alterations. Our present results indicate that chronic cerebral hypoperfusion
      produces oxidative stress and disturbs intracellular redox regulation in two
      distinct phases: at 1 day, "acute" and at 6 weeks, "chronic" alterations after
      the operation. Therefore, striatal neural cell damage may be mainly attributed to
      the transient increase of NOx production at 1 day after, and the delayed
      reduction of muscarinic acetylcholine receptor binding in the striatum may be
      mostly attributed to the continuous depression of GSH content from the 1st to the
      6th postoperative week. In particular, the continuous GSH depression may be
      considered to accompany the pathophysiology of chronic cerebral hypoperfusion.

PMID- 11958537
TI  - Complestatin antagonizes the AMPA/kainate-induced neurotoxicity in cultured chick
      telencephalic neurons.
AB  - Excitatory amino acids are known to induce considerable neurotoxicity in central
      nervous system. In the present study, the neurotoxicity was induced by
      application of kainate or AMPA in chick telencephalic neuron, and neuroprotective
      activity was tested with complestatin that was isolated from streptomyces
      species. In cultured telencephalic neurons exposed to 500 microM kainate for 2
      days, the AMPA/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione
      (DNQX, 5 microM) completely blocked kainate-induced neurotoxicity. Also,
      complestatin (0.5 microM) completely blocked kainate-induced neuronal injury at a
      concentration lower than that required for prototype AMPA/kainate receptor
      antagonist DNQX. In addition, complestatin blocked AMPA-induced neurotoxicity
      when the neurons were pretreated with cyclothiazide, a desensitization blocker of
      AMPA receptor. Surprisingly, when the onset of the treatment was delayed for 6
      hours, complestatin led to a reduction in kainate-induced neuronal injury. While
      inhibition of protein kinase C (PKC) by staurosporin induced neurotoxicity, that
      was blocked by complestatin. Activation of PKC by phorbol dibutyrate partially
      inhibited the kainate-induced neurotoxicity. These results suggest that
      complestatin may be used as an anti-excitotoxic agent and involved in the PKC
      activation contributing to inhibition of neurotoxicity.

PMID- 11958539
TI  - Including measured genotypes in statistical models to study the interplay of
      multiple factors affecting complex traits.
AB  - The etiology of complex traits may perhaps best be conceptualized by an interplay
      of multiple factors that mediate the influence of the genes on the eventual
      outcome. The possibilities of studying aspects of this interplay using existing
      methods are generally limited. We therefore propose a model with observed and
      latent variables that does not impose restrictions on the number of variables or
      the direction of their causal relations and provides a general approach for
      fitting structural equation models to empirical data. The model is very flexible
      and (1) allows for genetic effects on the means, variances, and relations between
      variables, (2) can control for stratification effects on all these components,
      (3) can be fitted in nuclear families of any size, (4) is estimated using an
      interpretable parameterization, and (5) can incorporate di- and multi-allelic
      loci, marker haplotypes, multiple loci simultaneously, and parental genotypes. We
      indicate how the model can be estimated with the Mx software (Neale et al., 1999)
      and have written a program to enable geneticists who are not acquainted with Mx
      to fit their own submodels in a simple and efficient way. A simulation study
      showed that the model yielded correct Type I errors, unbiased parameter
      estimates, and satisfactory power to discriminate between alternative models. An
      example is also given that illustrates how the model could be applied to real
      data.

PMID- 11958538
TI  - DNA damage in astrocytes exposed to fumonisin B1.
AB  - Fumonisins are a group of toxic metabolites mainly produced by Fusarium
      moniliforme and Fusarium proliferatum, fungi that commonly occur on corn
      throughout the world. Fumonisin B1 (FB1), structurally resembling sphingoid
      bases, is an inhibitor of ceramide synthase, a key enzyme involved in de novo
      sphingolipid biosynthesis and in the reacylation of free sphingoid bases derived
      from sphingolipid turnover. This inhibitory effect leads to accumulation of free
      sphinganine (SA) and sphingosine (SO), inducing cell death. However, little is
      known on the down stream effectors activated by these sphingolipids in the cell
      death signaling pathway. We exposed rat astrocytes to FB1 with the aim of
      evaluating the involvement of oxygen free radicals and of some other biochemical
      pathways such as caspase-3 activity and DNA damage. Our results indicate that FB1
      treatment (48, 72 h and 6 days in vitro, DIV, and 10, 50, 100 microM) does not
      affect cell viability. Conversely, after 72 h of treatment, FB1 (50 and 100
      microM) induced DNA damage and an enhancement of caspase-3 activity compared to
      controls. In addition, FB1 increased the expression of HSP70 at 10 and 50 microM
      at 48, 72 h, and 6 DIV of treatment. We conclude that DNA damage of apoptotic
      type in rat astrocytes is caused by FB1 and that the genotoxic potential of FB1
      has probably been underestimated and should be reconsidered.

PMID- 11958540
TI  - Power and sample sizes for linkage with extreme sampling under an oligogenic
      model for quantitative traits.
AB  - Extreme sampling of sibling pairs has been shown to be efficient in terms of
      statistical power and sample sizes (in number of sibling pairs needed to
      genotype) to detect a quantitative trait locus (QTL) when the residual
      distribution is normal. In the present study, the efficiency of extreme sampling
      strategies to detect each locus under an oligogenic model is analytically
      explored with a test statistic based on identical-by-descent (IBD) statuses of
      independent sibling pairs. In the oligogenic model, the joint effect of
      oligogenes is the sum of the effects of each locus. Under this model, detecting
      each single locus will depend, in part, on the allele frequencies and magnitudes
      of effect of the other loci. Effects of two QTLs with different magnitudes of
      displacement and acting nonepistatically are considered. Three types of extreme
      sampling-that is, extreme concordant high (ECH), extreme concordant low (ECL),
      and extreme discordant (ED)-are primarily considered herein. Among these, ED
      sampling under the oligogenic model is shown to be most efficient in most
      situations considered here in terms of allele frequency and mode of inheritance.
      Differences in results between ECH and ECL sampling are purely arbitrary, brought
      up mostly by the directions of displacement effects. However, power to detect a
      locus with the lesser (in magnitude) displacement effect does not necessarily
      increase with extremity of sampling. Combinations of extreme discordant and
      extreme concordant sibling pairs are briefly discussed.

PMID- 11958541
TI  - The mixed or multilevel model for behavior genetic analysis.
AB  - We propose the mixed model or multilevel model as a general alternative approach
      to existing behavior genetic analysis-an alternative to correlation analysis, the
      DeFries-Fulker analysis, and structural equation modeling. The mixed or
      multilevel model handles readily families of behavioral genetic data, which
      include paired sibling data (e.g., pairs of MZ and DZ twins) and clustered
      sibling data (e.g., a family of more than two biological siblings) as special
      cases. Not only can a family of behavioral genetic data have more than two
      siblings, it can also contain multiple types of siblings (e.g., a pair of MZ
      twins, a pair of DZ twins, a full sibling, and a half sibling). In contrast to
      the traditional approaches, the mixed or multilevel model is insensitive to the
      order of the siblings in a sibling cluster. We apply our approach to a large,
      nationally representative behavior genetic sample collected recently by the Add
      Health Study. We demonstrate the approach through several applications using both
      clustered and family complex behavioral genetic data: conventional variance
      decomposition analysis, analysis of interactions between genetic and
      environmental influences, and analysis of the possible genetic basis for
      friendship selection. We compare results from the mixed or multilevel model,
      Pearson's correlation analysis, and the structural equation model.

PMID- 11958542
TI  - Genome scanning of the HXB/BXH sets of recombinant inbred strains of the rat for
      quantitative trait loci associated with conditioned taste aversion.
AB  - In the current study, we searched for quantitative trait loci (QTL) responsible
      for a conditioned taste aversion (CTA) measured as a decrease in the intake of a
      saccharin conditioned stimulus followed by an i.p. injection of 0.15 M LiCl
      (lithium chloride) (2 ml/100 g body weight). A genome scanning for QTL associated
      with CTA was performed in the HXB/BXH sets of recombinant inbred (RI) strains
      derived from the Brown Norway (BN-Lx) rat and the spontaneously hypertensive rat
      (SHR). The BN-Lx progenitor showed a significantly stronger CTA (8.3+/-2.8%) than
      the SHR progenitor (27.8+/-3.3%, p < .0001). The distribution of CTA values among
      RI strains was continuous, suggesting a polygenic mode of inheritance. Genome
      scanning of RI strains with more than 700 gene markers revealed a significant
      association of CTA with the D2Cebr11s4 marker on chromosome 2 (LRS = 22.7) and
      with the D4Cebrp149s8 marker on chromosome 4 (LRS = 23.4). The chromosome 2
      putative QTL was confirmed by detecting a significant difference in CTA between
      the SHR progenitor (27.8+/-3.3%) and the SHR-2 (SHR.BN-D2Rat171/D2Arb24) congenic
      strain (13.1+/-4.4%, p < .01) that are genetically identical except for a segment
      of chromosome 2 that was transferred onto the genetic background of the SHR from
      the BN strain.

PMID- 11958543
TI  - Mapping of QTL influencing saccharin consumption in the selectively bred alcohol
      preferring and -nonpreferring rat lines.
AB  - The inbred preferring (iP) and nonpreferring (iNP) rat strains were derived from
      the selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) lines.
      Previously, 381 iP x iNP F2 progeny were generated to identify quantitative trait
      loci (QTLs) influencing alcohol consumption and preference. Saccharin consumption
      (ml/48 h) and saccharin intake (ml/kg/day) were also measured in the F2 sample
      and were significantly correlated with both alcohol consumption and preference
      (all r > or = .20, p < .0001), suggesting that there might be some QTLs
      influencing both saccharin and alcohol phenotypes. We have performed a genome
      screen using F2 animals with extreme saccharin or alcohol consumption to identify
      QTLs contributing to saccharin-related phenotypes. Lod scores greater than 2.0
      were found on chromosomes 3, 16 and 18 in this sample. Additional genotyping was
      performed in these regions in the full sample of 381 F2 progeny to further
      characterize these putative QTLs. On chromosome 3, the maximum lod score in the
      full sample was 2.7 with saccharin consumption. This QTL appears to overlap with
      a QTL identified for alcohol consumption in the iP and iNP lines and has
      pleiotropic effects on both phenotypes. Interestingly, this region of rat
      chromosome 3 is syntenic with mouse chromosome 2, where a QTL influencing alcohol
      preference has been previously reported. The QTL on chromosome 16 has a maximum
      lod score of 4.0 with saccharin intake and 2.6 with saccharin consumption. The
      QTL on chromosome 18 has a maximum lod score of 2.7 with saccharin consumption.
      Taken together, these data provide the first results of a genome screen for QTLs
      contributing to saccharin phenotypes in the rat.

PMID- 11958544
TI  - Two QTLs located on chromosomes 1 and 5 modulate different aspects of the
      performance of mice of the B x D Ty RI strain series in the Morris navigation
      task.
AB  - The Morris navigation task is widely used to study spatial abilities in rodents;
      namely, to analyze the effects of mutations in genetically engineered mice.
      Although quantitative and Mendelian genetic studies have shown that the variation
      of these abilities is partly under genetic control, little is known about these
      genetic factors. In order to analyze the genetic architecture of spatial
      navigation in mice, a wide genome scan was performed to map the QTLs that control
      various aspects of the performance, using the RI strain methodology. Latencies to
      locate the submerged platform across learning sessions and performance to the
      spatial probe test were analyzed in the 26 strains of the B x D RI series. Both
      cluster analysis of behavioral measurements and QTL mapping confirmed previous
      data showing that the escape latencies and the spatial bias rely on two distinct
      components of the task, controlled by different loci. A QTL on chromosome 1
      influenced escape latencies during the four training sessions, whereas another
      QTL, located on chromosome 5, was shown to control spatial performance at the
      probe trial and also exhibited epistatic interactions with two other QTLs on
      chromosomes 2 and 13. The function of these QTLs is examined in the broader
      context of hippocampal-dependent learning processes and in relation to QTLs
      already found in similar positions in other behavioral traits.

PMID- 11958545
TI  - Factor analysis of olfactory responses in Drosophila melanogaster enhancer-trap
      lines as a method for ascertaining common reception components for different
      odorants.
AB  - Olfactory information is transmitted to the brain using combinatorial receptor
      codes; consequently, a single reception element can be activated by different
      odorants. Several methods have been applied to describe from a functional point
      of view those odorants sharing olfactory reception components. A genetic approach
      in Drosophila melanogaster used correlation between behavioral responses to
      different odorants for deducing common olfactory pathway-genes. A factor analysis
      applied to behavioral responses to five odorants of 27 antennal enhancer-trap
      lines revealed three components, explaining 82.1% of the total observed variance.
      A first factor affects simultaneously the response to ethyl acetate,
      propionaldehyde, and acetone. A second factor was related to responses to ethyl
      acetate, ethyl alcohol, and acetone, and, finally, the third factor associates
      responses to acetic acid and ethyl acetate. They contribute by 35.1%, 36.9%, and
      28%, respectively, to the explained variance.

PMID- 11958546
TI  - Fallout from the Chernobyl nuclear disaster and congenital malformations in
      Europe.
AB  - Investigators estimate that the population exposure that resulted from the
      Chernobyl fallout is in the range of natural background radiation for most
      European countries. Given current radiobiologic knowledge, health effects-if any
      would not be measurable with epidemiologic tools. In several independent reports,
      however, researchers have described isolated peaks in the prevalence of
      congenital malformations in the cohort conceived immediately after onset of the
      fallout. The consistency of the time pattern and the specific types of
      malformation raise concern about their significance. In this study, the author
      summarizes findings from Turkey, Belarus, Croatia, Finland, Germany, and other
      countries, and implications for radiation protection and public health issues are
      discussed.

PMID- 11958547
TI  - Infections and atopic disorders in childhood and organochlorine exposure.
AB  - The authors investigated whether organochlorine exposure is associated with
      prevalence of otitis media, pneumonia, pertussis, asthma, and increased
      immunoglobulin E levels in children. Organochlorine concentrations and histories
      of infection and atopic manifestation were available for 343 children, and
      immunoglobulin E levels were available for 340 children. The authors applied
      logistic and linear regressions and controlled for confounders. In general, the
      prevalence of infections in children was not related to organochlorine exposure.
      However, for the combined effect of dichlorodiphenyldichloroethene with
      polychlorinated biphenyls or hexachlorobenzene, a significantly increased
      relative risk (odds ratios = 3.70 and 2.38, respectively) was found for otitis
      media. Exposure to dichlorodiphenyldichloroethene resulted in a significantly
      higher odds ratio for asthma (odds ratio = 3.71; 95% confidence interval = 1.10,
      12.56) and in immunoglobulin E concentrations above 200 kU/l (odds ratio = 2.28;
      95% confidence interval = 1.20, 4.31). This is the first study in which
      dichlorodiphenyldichloroethene has been identified as a substantial risk factor
      for asthma and for increased immunoglobulin E blood levels.

PMID- 11958549
TI  - Low-level lead exposure and blood lead levels in children: a cross-sectional
      survey.
AB  - The authors studied 53 girls (44.5%) and 66 (55.5%) boys in Karachi, Pakistan, to
      determine their blood lead levels. The association between blood lead
      levels/water lead levels and the possible risk factors and symptoms associated
      with lead toxicity was explored. The mean lead level for the entire group was 7.9
      microg/dl (standard deviation = 4.5 microg/dl). Thirty (25.2%) of the children
      had lead levels that exceeded 10 microg/dl; 12 (10.0%) of these had lead levels
      that exceeded 15 microg/dl. Thirteen (20.9%) of the children under the age of 6
      yr (n = 62) had lead levels greater than 10 microg/dl, and 6 (9.6%) had levels in
      excess of 15 microg/dl. The authors found no association (p > .05) between high
      lead levels in water and blood lead levels in children. Mean blood lead levels
      were highest in the group of children exposed to various risk factors for lead
      absorption (e.g., exposure to paint, remodeling, and renovation; use of lead
      utensils; pica). There was a significant association between a history of
      exposure to paint/renovation activities and a history of pica. High blood lead
      levels in the children in Karachi stress the urgency for actions that control
      lead pollution. Screening programs should be instituted by the state. Individuals
      must become aware of lead's toxicity, and they must avoid substances that contain
      lead.

PMID- 11958548
TI  - Biochemical, neuropsychological, and neurological abnormalities following 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) exposure.
AB  - Presented herein are the results of follow-up examinations of 13 workers
      performed in 1996--30 yr following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      intoxication in a herbicide production plant. In these workers, the current mean
      plasma level of 2,3,7,8-TCDD, measured by high-resolution gas chromatography/high
      resolution mass spectrometry, was 256 pg/gm lipid (range = 14-760 pg/gm lipid).
      This mean value corresponded to an estimated concentration of approximately 5,000
      pg/gm plasma fat that existed about 30 years ago. Such a mean plasma level
      indicates that this group was one of the most heavily exposed groups to 2,3,7,8
      TCDD described in the literature. Patients with persistent chloracne had
      significantly higher plasma levels of 2,3,7,8-TCDD than persons without
      chloracne. A significant, positive correlation was found between plasma levels of
      2,3,7,8-TCDD in 1996 and levels of cholesterol and plasma lipids that existed
      since 1974. During 1996, there was a significant positive correlation between
      2,3,7,8-TCDD and levels of beta-lipoproteins, cholesterol, and triglycerides.
      Also in 1996, significant correlations were found between neuropsychological
      variables and plasma levels of 2,3,7,8-TCDD. Other significant correlations were
      observed between neuropsychological variables and (1) the highest levels of
      triglycerides (i.e., since the year 1989), (2) levels of triglycerides in 1996,
      (3) levels of cholesterol at the first examination (i.e., 1969-1970), (4) highest
      level of cholesterol since the year 1969, and (5) cholesterol levels in 1996.
      Such correlations are biologically plausible, and they provide evidence of
      impaired cognitive performance (i.e., memory first), with a concurrent increase
      of plasma lipid levels. Abnormal electromyography, electroencephalography, and
      visual evoked potentials were observed in 23%, 54%, and 31 %, respectively, of
      former workers. Abnormal electroencephalography findings occurred more frequently
      in workers who had 2,3,7,8-TCDD blood levels that exceeded 200 pg/gm plasma fat
      than in workers with 2,3,7,8-TCDD values lower than 200 pg/gm plasma fat (p <
      .025). Frequency of polyneuropathic EMG abnormalities decreased from 38% in the
      1970s to 23% in 1996. Improvement of conduction velocity in the tibial nerve was
      statistically significant (p < .05).

PMID- 11958550
TI  - Assessment of exposure to polycyclic aromatic hydrocarbons in police in Florence,
      Italy, through personal air sampling and biological monitoring of the urinary
      metabolite 1-hydroxypyrene.
AB  - In this study, the authors evaluated exposure to airborne polycyclic aromatic
      hydrocarbons (PAHs) in workers exposed to exhaust gas from cars, and they
      assessed the efficiency of urinary 1-hydroxypyrene as an indicator of exposure to
      pyrene and PAHs. The authors selected 2 groups of police who worked in 2 areas in
      the city of Florence: 1 group was highly exposed to high-density traffic
      emissions during the winter and summer of 1997, and the 2nd group experienced low
      exposure to traffic emissions during the same period. Ambient monitoring was
      achieved with personal sampling of airborne PAHs during each workshift. Eight
      hydrocarbons were used as indicators of pollution caused by PAHs (e.g., pyrene,
      benzo[a]pyrene, benzo[a]anthracene, dibenzo[a,h]anthracene). Biological
      monitoring was performed through dosing of 1-hydroxypyrene (pyrene metabolite) in
      urine samples taken at the end of each workshift. The ambient monitoring revealed
      that PAH concentrations were influenced by both season of sampling and varying
      intensities of traffic in the different areas. The median concentration of
      benzo[a]pyrene in winter was twice as high in the high-density traffic area as in
      the low-density traffic area (i.e., 4.1 ng/m3 versus 1.8 ng/m3). In summer, the
      high-density traffic area experienced benzo[a]pyrene concentrations that were 6
      times higher than in the low-density traffic area (i.e., 1.2 ng/m3 versus 0.2
      ng/m3). Benzo[a]pyrene was also correlated highly (r(s) = .92, p < .0001) with
      the mixture of total PAHs analyzed, thus confirming its function as a good
      indicator of exposure to PAHs in an urban environment. Levels of urinary 1
      hydroxypyrene appeared to be generally influenced by the intensity of traffic,
      especially during the winter (i.e., median value in winter was 199.2 ng/gm
      creatinine in the high-density traffic area and 120.5 ng/gm creatinine in the low
      density traffic area). An analysis of the general data revealed that 1
      hydroxypyrene was, to some degree, related to pyrene, benzo[a]pyrene, and
      airborne total PAHs, whereas analysis of separate data for the area and the
      season revealed an emergence of a closer correlation during the winter in the
      high-traffic area. Therefore, 1 -hydroxypyrene can be considered a good
      biological indicator of exposure to airborne PAHs in the urban environment,
      especially in winter and in high-density traffic areas.

PMID- 11958551
TI  - Pulmonary deposition of particles in welders: on-site measurements.
AB  - The authors used integrating nephelometers to demonstrate the feasibility of
      measuring particulate matter with a diameter of 2.5 microm (PM2.5) in the
      breathing zone and PM2.5 mass deposition in the airways of 6 welders at their
      place of work. The authors also measured stationary PM2.5 measurements. The
      between-subject variation in deposition of PM2.5 mass was approximately 1/3 of
      the within-subject variation. Smokers had a significantly higher total
      respiratory system deposition than nonsmokers. The PM2.5 deposition for a given
      amount of exhaled air was dependent on PM2.5 concentration levels. The estimated
      total amount of PM2.5 deposited in the respiratory system of the subjects was
      approximately 1 mg/day.

PMID- 11958553
TI  - Addressing environmental health concerns near Trecatti landfill site, United
      Kingdom.
AB  - Residents near the Trecatti landfill site located in South Wales, United Kingdom,
      expressed concern about odors and health effects they attributed to site
      emissions. The authors compared routinely collected, population-based, health
      data from potentially exposed electoral wards (i.e., United Kingdom electoral
      tracts) with data from both wards nearby, matched for socioeconomic deprivation
      scores, and with wards where residents were likely to attend the same hospital.
      Mortality rates were higher for all causes and neoplastic diseases (but not
      respiratory disease) in the exposed wards, but there was no change in rates after
      the site opened. Hospital data revealed a transient increase in admissions for
      asthma during the 3 yr that preceded the peak in odor complaints. The birth
      prevalence of congenital malformations was raised in the exposed wards, but the
      authors could not exclude a possible artifact resulting from differences in
      reporting practices between hospitals. The absence of environmental monitoring in
      the community during the period of public concern was a significant weakness of
      this study.

PMID- 11958552
TI  - Developmental dental defects in children who reside by a river polluted by
      dioxins and furans.
AB  - The authors determined that demarcated hypomineralizations of developing teeth
      are a biological indicator of an early dioxin exposure in a healthy population of
      children. In the current study, the authors examined the prevalences of the
      demarcated hypomineralization lesions of teeth in 2 Finnish towns by the Kymijoki
      River--a river that is severely contaminated by dioxins and furans. The 4,120
      permanent first molars of 1,030 children were studied. The prevailing levels of
      dioxins and furans in human milk were measured. The prevalences of the defects in
      children in Kotka and Anjalankoski were 14.2% and 5.6%, respectively, and the
      corresponding dioxins and furans in human milk were 13.4 pg/gm fat and 10.9 pg/gm
      fat (International Toxic Equivalents). In Anjalankoski, the duration of total
      breast-feeding was associated with the prevalence of the defects. Compared with
      the figures reported earlier in Finland, neither the prevalence of dental lesions
      nor the levels of dioxins and furans in human milk were increased in riverside
      residents.

PMID- 11958554
TI  - Recent trends in childhood blood lead levels.
AB  - Blood lead levels in children in the United States have declined through 1994,
      the date of the most recent National Health and Nutrition Examination Survey. In
      this investigation, the authors analyzed whether blood lead levels have changed
      since 1994 and quantified the magnitude of any change. The authors evaluated
      blood lead levels from 12 longitudinal data sets from 11 states and 1 city.
      Geometric mean blood lead levels declined between 4%/year and 14%/year in 8 of
      the data sets. No differences in decline rates were observed between data sets
      from states that had universal screening as a goal or that included repeat
      measures for an individual child and those data sets that did not. The authors'
      best estimate for these populations was a decline rate of 4-7%/year, which was
      comparable to the decline rate prior to 1994.

PMID- 11958555
TI  - Estimated change in blood lead concentration in control populations.
AB  - Investigators have conducted several studies to assess the effectiveness of lead
      hazard interventions in reducing children's blood lead levels. For practical and
      ethical reasons, many of these studies have not included control populations. It
      is, therefore, impossible for researchers to determine to what extent the
      reported decline in blood lead concentrations has resulted from intervention
      versus other factors. In the current retrospective analysis, the authors
      estimated the change in children's blood lead levels in control populations at 12
      mo follow-up. The results suggest that an average 9% decline may be attributed to
      factors that are unrelated to intervention. Declines of approximately 25% have
      been reported following several lead-hazard interventions. For these studies, the
      results of the authors' analysis suggest that approximately 16% of the decline is
      attributed directly to the intervention.

PMID- 11958557
TI  - Consumption of wine stored in leather wine bottles and incidence of gastric
      cancer.
AB  - The authors conducted a survey among participants of a large-scale case-control
      study to evaluate a possible association between consumption of wine in leather
      bottles and incidence of gastric cancer. There were 59 cases and 53 controls in
      the study. The results suggest that some of the components of the complex mixture
      (i.e., tar) used in the proofing of leather wine bottles might dissolve in the
      wine and participate in the etiology of gastric cancer. Nevertheless, the results
      should be confirmed in an independent study.

PMID- 11958556
TI  - Exposure to traffic pollution: comparison between measurements and a model.
AB  - French researchers from the Building Scientific and Technical Center have
      produced a traffic-exposure index. To achieve this, they used an air pollution
      dispersion model that enabled them to calculate automobile pollutant
      concentrations in front of subjects' residences and places of work. Researchers
      used this model, which was tested at 27 Paris canyon street sites, and compared
      nitrogen oxides measurements obtained with passive samplers during a 6-wk period
      and calculations derived from the model. There was a highly significant
      correlation (r = .83) between the 2 series of values; their mean concentrations
      were not significantly different. The results suggested that the aforementioned
      model could be a useful epidemiological tool for the classification of city
      dwellers by present-or even cumulative exposure to automobile air pollution.

PMID- 11958558
TI  - Arsenicism in India: dermal lesions and hair levels.

PMID- 11958559
TI  - Receptor-dependent transcriptional activation of cytochrome P4503A genes:
      induction mechanisms, species differences and interindividual variation in man.
AB  - 1. The importance of CYP3A enzymes in drug metabolism and toxicology has yielded
      a wealth of information on the structure, function and regulation of this
      subfamily and recent research emphasis has been placed on the human forms, namely
      CYP3A4, CYP3A5, CYP3A7 and CYP3A43. 2. The current review will focus on the
      receptor-dependency of CYP3A regulation and includes consideration of the
      regulatory roles of the glucocorticoid (GR), pregnane X (PXR) and constitutive
      androstane (CAR) receptors. 3. Emphasis has been placed on the topics of
      expression and substrate specificity, assessment of induction, species
      differences in induction, CYP3A promoter sequences and regulation of gene
      expression, structural and functional aspects of receptor-mediated, CYP3A gene
      activation, receptor variants and interindividual variation in human CYP3A
      expression, the latter encompassing environmental, physiological and genetic
      aspects. 4. An outline of future research needs will be discussed in the context
      of receptor-mediated molecular mechanisms of CYP3A gene regulation and the impact
      on interindividual variations in CYP3A expression. 5. Taken collectively, this
      review highlights the importance of understanding the molecular mechanisms of
      CYP3A induction as a means of rationalizing human responses to many clinically
      used drugs, in addition to providing a mechanistically coherent platform to
      understand and predict interindividual variations in response and drug-drug
      interactions.

PMID- 11958561
TI  - SB-242235, a selective inhibitor of p38 mitogen-activated protein kinase. I:
      preclinical pharmacokinetics.
AB  - 1. SB-242235 (1-(4-piperidinyl)-4-(4-fluorophenyl)-5-(2-methoxy-4-pyrimidinyl)
      imidazole) is a potent and selective p38 MAP kinase inhibitor that may be an
      effective therapy for cytokine-mediated diseases such as autoimmune or
      inflammatory diseases. The present studies were conducted to evaluate the
      pharmacokinetics of SB-242235 in several preclinical species, including rat, dog
      and monkey. 2. SB-242235 demonstrates generally favourable pharmacokinetic
      properties in all species examined. Systemic plasma clearance was high in rat,
      but in the non-rodent species SB-242235 demonstrated low to moderate clearance
      with plasma half-lives > 4h. Oral bioavailability in each preclinical species was
      high. In rat and monkey, SB-242235 demonstrated non-linear elimination kinetics
      that manifested as a decrease in clearance with increasing dose and apparent oral
      bioavailability > 100% at high oral doses. Furthermore, SB-242235 displayed
      concentration-dependent plasma protein binding over a concentration range of 1000
      10,000 ng ml(-1). 3. In conclusion, SB-242235 demonstrates high oral
      bioavailability across the major preclinical species, and may thus be a useful
      tool compound for investigation of the role of p38 inhibition in various disease
      states. However, the observations of non-linear protein binding and disposition
      also suggest the need for caution in the design of and data interpretation from
      such studies.

PMID- 11958560
TI  - Differences in the absorption, metabolism and biliary excretion of a
      diastereomeric pair of alphavbeta3-antagonists in rat: limited role of P
      glycoprotein.
AB  - 1. The study investigated mechanisms underlying the pharmacokinetic differences
      of two zwitterionic diastereomers ((3S)-3-[(3R or 3S)-2-oxo-3-[3-(5,6,7,8
      tetrahydro-1,8-naphthyridin-2-yl)propyl]pyrrolidin-1-yl]-3-quinolin-3-ylpropanoic
      acid) with different lipophilicities using a combination of in vivo and in vitro
      approaches. 2. In rat, both isomers possessed comparable plasma clearances (CL).
      However, the more lipophilic diastereomer I exhibited a higher metabolic
      clearance (>2-fold higher than II), whereas the hydrophilic zwitterion II
      exhibited a higher biliary clearance (approximately 5-fold higher than I).
      Following oral administration, the bioavailability (F) of I (17%) was much higher
      than that of II (1%). 3. Consistent with these in vivo observations and the
      expectation based on their lipophilicity differences, the metabolism in rat liver
      microsomes was faster and the permeability in Caco-2 and LLC-PK1 cells and in
      situ rat intestinal loop was better for I than for II. 4. Only the absorption of
      the more lipophilic diastereomer I was subjected to an efflux system in the Caco
      2 and in situ rat intestinal loop models. I was a good substrate for P
      glycoprotein (P-gp) in both the human MDR1 and mouse mdr1a transfected cell
      lines, and in the wild-type mdr1a (-/-) mouse when compared with the P-gp
      deficient mdr1a (-/-) mouse. Concomitant administration of I with verapamil in
      rat caused significant increases in oral AUC, F and Cmax of I without affecting
      its CL, further supporting the effect of P-gp in limiting the intestinal
      absorption of I in vivo in this animal model. 5. Since the findings that the
      lipophilic diastereomer I, but not II, was a good P-gp substrate were not in line
      with the observations that I was excreted to bile much slower than II and that I
      was absorbed better than II, the results suggested that P-gp played a minor role
      to the observed differences in the biliary excretion and intestinal absorption of
      the diastereomers I and II in rat.

PMID- 11958562
TI  - SB-242235, a selective inhibitor of p38 mitogen-activated protein kinase. II: in
      vitro and in vivo metabolism studies and pharmacokinetic extrapolation to man.
AB  - 1. Inhibition of p38 MAP kinase has been investigated extensively as a potential
      therapy for cytokine-mediated diseases such as autoimmune and inflammatory
      diseases. SB-242235 (1-(4-piperidinyl)-4-(4-fluorophenyl)-5-(2-methoxy-4
      pyrimidinyl) imidazole) is a potent and selective p38 MAP kinase inhibitor; the
      preclinical pharmacokinetics of SB-242235 have been described previously. The
      present studies were conducted to describe the in vitro metabolic rates and
      routes of SB-242235 metabolism, to characterize its in vivo preclinical
      metabolism, and to use these data to aid in the prediction of the pharmacokinetic
      behaviour of SB-242235 in man. 2. SB-242235 was metabolically stable in rat, dog,
      monkey and human hepatic microsomes, isolated hepatocytes and liver slices in
      vitro. The in vivo preclinical metabolism studies were consistent with the in
      vitro findings; SB-242235 was minimally metabolized, and was primarily excreted
      unchanged in the urine (45 and 67% of the administered dose in the rat and
      monkey, respectively). 3. Allometric scaling using various correction factors
      predicted that SB-242235 would have low clearance in man with a predicted half
      life ranging from 11.5 to 18.7h. This prediction was consistent with the observed
      mean half-life of 16.4h in the first-in-man study for SB-242235. An allometric
      scaling method with a correction for interspecies differences in glomerular
      filtration rate provided the most accurate prediction of the pharmacokinetic
      behaviour of SB-242235 in humans, although the clinical data also highlight
      potential difficulties in conducting prospective allometry.

PMID- 11958563
TI  - Sequence analysis of pLBB1, a cryptic plasmid from Lactobacillus delbrueckii
      subsp. bulgaricus.
AB  - The first report of the complete nucleotide sequence of a cryptic plasmid from
      Lactobacillus delbrueckii subsp. bulgaricus (Lactobacillus bulgaricus) is
      presented. The plasmid pLBB1 consists of 6127 bp with a GC content of 44.8%. No
      ssDNA was detected by hybridization experiments, which is consistent with the
      notion that pLBB1 does not replicate by a rolling circle mechanism. A putative
      replication region of pLBB1 was cloned and found to be functional in
      Lactobacillus johnsonii and Lactococcus lactis. Plasmid pLBB1 showed significant
      DNA sequence identity with plasmid pLL1212 from Lactobacillus delbrueckii subsp.
      lactis (Lactobacillus lactis) CRL1212 (GenBank accession No. AF109691). Four open
      reading frames (ORFs) larger than 100 amino acids were identified. ORFA shared
      similarity with a putative primase-helicase system, and ORFB and ORFC exhibited
      limited identity with a mobilization protein and a transposase, respectively.
      Curing experiments did not allowed us to assign a function to the ORFs.

PMID- 11958564
TI  - Development of oligonucleotide primers for the specific PCR-based detection of
      the most frequent Enterobacteriaceae species DNA using wec gene templates.
AB  - Oligonucleotide primers were designed for the PCR-based detection of the wec gene
      cluster involved in the biosynthetic pathway leading to the production of
      enterobacterial common antigen (ECA). Escherichia coli DNA was detected using wec
      A, wec E, and wec F gene primers. The wec A primers were specific for E. coli.
      The wec E and wec F primers enabled the detection of the most frequent species of
      the Enterobacteriaceae found in blood and urine specimens as well as in water.
      The sensitivity of the assay was approximately 1.2 x 102 bacteria/mL of water.
      Thus, these primers represent an important step in the molecular diagnosis of
      major Enterobacteriaceae infections. Their role in the routine testing of
      contamination in drinking water and food may prove to be very useful. The DNA of
      Enterobacteriaceae species is detected in a first step PCR, followed by specific
      identification of important pathogens like E. coli O157, Shigella spp.,
      Salmonella spp., and Yersinia spp.

PMID- 11958565
TI  - Early interactions of Entamoeba histolytica trophozoites with parenchymal and
      inflammatory cells in the hamster liver: an immunocytochemical study.
AB  - We studied the early in situ interactions of live and fixed Entamoeba histolytica
      trophozoites with hamster hepatic parenchymal and inflammatory cells using
      immunoperoxidase and immunoelectronmicroscopy. Close contact between trophozoites
      and endothelial cells and the diffusion of amoebic molecules from trophozoites
      towards nearby endothelial cells and distant hepatocytes were observed. The
      inflammatory cells around the amoebae and the remnants of parenchymal cells and
      hepatocytes located close to the lesion had a positive stain for amoebic
      molecules. In the amoebae, at the ultrastructural level, molecules were attached
      to the membranes and inside the vesicles. These molecules were apparently
      released into the space formed between the parasite and the endothelial cells.
      The endothelial cells and the nearby and distant hepatocytes captured amoebic
      molecules, and later they became necrotic. Contrarily, when fixed amoebae were
      inoculated, amoebic molecules were captured by endothelial cells and
      polymorphonuclear (PMN) leukocytes, but neither suffered any damage. In this
      work, we are presenting evidence clearly showing that some molecules of the
      amoeba can diffuse away long distances causing cytotoxic effects and even
      necrosis on hepatic cells of hamster liver without the need of the trophozoite
      being in close contact with the target cells. They also may promote lytic or
      proinflammatory effects by inducing the secretion of enzymes or cytokines in
      other nonparenchymal cells, like PMN leukocytes and endothelial cells. Our
      results suggest that the accepted mechanisms of cytotoxicity by amoebae are not
      exclusively restricted to the following sequence: adhesion, phagocytosis, and
      necrosis.

PMID- 11958566
TI  - Isolation of an Escherichia coil strain mutant unable to form biofilm on
      polystyrene and to adhere to human pneumocyte cells: involvement of
      tryptophanase.
AB  - Escherichia coli adherence to biotic and abiotic surfaces constitutes the first
      step of infection by promoting colonization and biofilm formation. The aim of
      this study was to gain a better understanding of the relationship between E. coli
      adherence to different biotic surfaces and biofilm formation on abiotic surfaces.
      We isolated mutants defective in A549 pneumocyte cells adherence, fibronectin
      adherence, and biofilm formation by random transposition mutagenesis and
      sequential passages over A549 cell monolayers. Among the 97 mutants tested, 80
      were decreased in biofilm formation, 8 were decreased in A549 cells adherence, 7
      were decreased in their adherence to fibronectin, and 17 had no perturbations in
      either of the three phenotypes. We observed a correlation between adherence to
      fibronectin or A549 cells and biofilm formation, indicating that biotic adhesive
      factors are involved in biofilm formation by E. coli. Molecular analysis of the
      mutants revealed that a transposon insertion in the tnaA gene encoding for
      tryptophanase was associated with a decrease in both A549 cells adherence and
      biofilm formation by E. coli. The complementation of the tnaA mutant with plasmid
      located wild-type tnaA restored the tryptophanase activity, epithelial cells
      adherence, and biofilm formation on polystyrene. The possible mechanism of
      tryptophanase involvement in E. coli adherence and biofilm formation is
      discussed.

PMID- 11958567
TI  - Maturation of barley cysteine endopeptidase expressed in Trichoderma reesei is
      distorted by incomplete processing.
AB  - Maturation of barley cysteine endopeptidase B (EPB) in Trichoderma reesei was
      studied with metabolic in hibitors, Western blotting, and immuno microscopy. The
      inactive 42-kDa recombinant EPB proprotein, first detected in apical cells, was
      sequentially processed in a time-dependent manner to a secreted polypeptide of
      38.5 kDa, and thereafter, to polypeptides of 37.5, 35.5, and 32 kDa exhibiting
      enzyme activity both in the hyphae and culture medium. The sizes of the different
      forms of recombinant EPB were in accordance with molecular masses calculated from
      the deduced amino acid sequence, assuming cleavage at four putative Kex2p sites
      present in the 42-kDa proprotein. Both the liquid and the zymogram in-gel
      activity assays indicated that the 32-kDa enzyme produced in T. reesei in vivo
      was 2 kDa larger and four times less active than the endogenous EPB. Brefeldin A
      treatment prevented the last Kex2p processing step of EPB from a 35.5- to a 32
      kDa protein. This coincided with a significant increase in the immuno-gold label
      for EPB and in modified Golgi-like bodies, which suggests that the processing
      step probably took place in medial Golgi. A 30.5-kDa EPB polypeptide was observed
      when glycosylation was inhibited by tunicamycin (TM) or when deglycosylation was
      carried out enzymatically. Deglycosylation increased the enzyme activity twofold,
      which was also indicated by an increased fluorescence by TM treatment in the
      zymogram in-gel activity assay. Simultaneous incubation with TM and monensin
      produced a peptide of 31.5 kDa. Therefore, monensin may inhibit the final
      processing step of an unglycosylated EPB by an unknown protease in the fungus. In
      any case, the final recombinant EPB product in Trichoderma differs from the
      mature endogenous 30-kDa enzyme produced in barley.

PMID- 11958568
TI  - Degradation of polycyclic aromatic hydrocarbons dissolved in Tween 80 surfactant
      solutions by Sphingomonas paucimobilis EPA 505.
AB  - The degradation rates of mixtures of pyrene (PYR), fluoranthene (FLA), and
      phenanthrene (PHE) by Sphingomonas paucimobilis EPA 505 were measured in the
      presence of the nonionic surfactant Tween 80. For strain EPA 505, FLA and PHE are
      growth substrates, while PYR is not. Linear degradation rates ranging from 0.05
      to 2.2 mg x L(-1) x h(-1) were observed for FLA, PYR, and PHE at approximately
      10(7) colony-forming units (CFU)/mL. At lower biomass, PYR degradation exhibited
      lognormal degradation. The degradation rates of PYR, FLA, and PHE increased with
      increasing biomass and substrate concentration. At high FLA concentrations, FLA
      degradation rates were faster in the presence of surfactant than in the absence
      of surfactant, suggesting that some of the FLA was transported directly into the
      cell from the micellar phase. In mixtures, PHE was the preferred substrate and
      was utilized first, followed by FLA and then PYR. Once the competing substrates
      were degraded, the remaining substrate was degraded at the same rate or faster
      than the rate found in the single-substrate system. Based on the results with
      Tween 80, it appears that PHE, PYR, and FLA are competing for the same enzymatic
      sites.

PMID- 11958569
TI  - Paenibacillus polymyxa produces fusaricidin-type antifungal antibiotics active
      against Leptosphaeria maculans, the causative agent of blackleg disease of
      canola.
AB  - A bacterial isolate capable of inhibiting the growth of Leptosphaeria maculans
      (Desmaz.) Ces. & De Not., the causative agent of blackleg disease of canola
      (Brassica napus L. and Brassica rapa L.), was identified as a potential
      biological control agent. This environmental isolate was determined to be
      Paenibacillus polymyxa based on its (i) biochemical and growth characteristics
      and (ii) 16S rRNA sequence similarity, and was given the strain designation PKB1.
      Antifungal peptides were produced by P. polymyxa PKB1 around the onset of
      sporulation, with optimal production on potato dextrose broth. The antifungal
      peptides were extracted from P. polymyxa PKB1 cells and (or) spores using
      methanol and were purified using size exclusion and reverse-phase chromatography.
      Characterization of the antifungal peptides was done using amino acid
      compositional analysis, Edman degradation sequencing from partially hydrolyzed
      material, and a variety of mass spectrometric methods. The purified antifungal
      material was found to be a mixture of related peptides of molecular masses 883,
      897, 948, and 961 Da, with the most likely structure of the 897 Da component
      determined to be a cyclic depsipeptide with an unusual 15-guanidino-3
      hydroxypentadecanoic acid moiety bound to a free amino group. These compounds are
      therefore members of the fusaricidin group of cyclic depsipeptides.

PMID- 11958570
TI  - Stimulatory effect of aerosil on algal growth.
AB  - Unicellular green alga represents not only a convenient model for its biochemical
      and physiological studies but also a sensitive system to test the effects of
      various environmental factors. Algae cells of two strains, SA-3 strain
      (exsymbiotic from Paramecium bursaria) and Chlorella vulgaris c-27, were
      asynchronously cultured in the presence of 0.01% Aerosil A-300. Aerosil effects
      on algae were monitored at logarithmic and stationary phases of their growth by
      flow cytometry and microscopic counting of algal numbers. The growth patterns of
      algae were evaluated by their forward light scatter versus fluorescence of
      endogenous chlorophyll (FL3-height) signal distributions. Although aerosil itself
      did not cause any direct effects on algal morphology, it affected the growth
      patterns and the numbers of algae of both strains. Their growth patterns were
      remarkably altered in the late logarithmic phase cultures (6-day cultures).
      However, a significant increase of cell numbers was found in the stationary phase
      cultures (9- and 12-day cultures). While C. vulgaris c-27 demonstrated an
      increase of cell numbers by approximately 11% in the 9- and 12-day cultures, the
      amounts of SA-3 cells in the 9- and 12-days cultures were increased by 16% and
      35%, respectively. Our study shows aerosil in its colloidal form stimulates
      proliferation of algae mainly via an acceleration of their life cycles. The
      stimulatory effect of silica on the growth of algae, the mechanism of which
      remains to be clarified, might have a practical (e.g., ecological) interest for
      regulation of algal expansion.

PMID- 11958571
TI  - Total microbial activity and microbial composition of a mangrove sediment are
      reduced by oil pollution at a site in the Arabian Gulf.
AB  - In a study carried out to determine the effect of oil pollution on the microbiota
      of sediment associated with mangroves in the United Arab Emirates, sediment
      samples were collected from oil-polluted and nonpolluted mangrove sites. The
      levels of the total recoverable hydrocarbons and the polycyclic aromatic
      hydrocarbons assayed were noticeably higher in the polluted sediment. Microbial
      activity as measured by the hydrolysis of fluorescein diacetate and by the total
      populations of the culturable aerobic and anaerobic bacteria, streptomycete and
      non-streptomycete actinomycetes, and filamentous fungi and yeasts was
      significantly (P < 0.05) lower in the polluted than in the nonpolluted sediment.
      The estimated total aerobic and anaerobic hydrocarbon-utilizing bacteria were
      significantly (P < 0.05) higher in the polluted than in the nonpolluted
      sediments. Four days after the addition of the water-soluble fractions of the
      light Arabian crude oil to the nonpolluted sediment, at 10 different
      concentrations, there was a significant (P < 0.05) reduction (65%) in the
      microbial activity of the sediment compared with that of nonamended sediment.
      Concentrations of water-soluble fractions at 0.1% and above significantly and
      progressively reduced microbial activity, with total cessation of activity
      recorded at levels >50%. This study is the first to evaluate the effect of oil
      pollution on aerobic and anaerobic microbial flora of sediment of mangrove
      communities.

PMID- 11958573
TI  - Changes in the clinical and laboratory features of lupus patients after the big
      earthquake in Taiwan.
AB  - In order to understand the impact of the massive earthquake on disease activity,
      60 patients with systemic lupus erythematosus (SLE) living in the earthquake area
      (group 1) and 31 patients living away from the area (group 2) were enrolled in
      this study. A questionnaire was used to record demographic data and clinical
      manifestations before and 6 months after the earthquake. Laboratory tests,
      including serum C3, C4, creatinine, anti-DNA antibody, CBC and 24 h urine protein
      were taken. The results showed that nine patients in group 1 had obvious disease
      flare-up as evidenced by fever, arthralgia, malar rash and photosensitivity,
      increased protein loss or edema, and other symptoms. However, there were no
      significant changes in either group 1 or 2 patients. In contrast, the comparison
      of laboratory parameters in group 1 patients before and after the earthquake
      showed a significant decrease of C4 from 17.3 +/- 15.3 to 14.1 +/- 7.33 and a
      significant increase of creatinine from 1.20 +/- 1.54 to 1.27 +/- 1.70 (P <
      0.05), respectively. No significant difference for either C4 or creatinine was
      found in group 2 patients. In conclusion, there was no striking change in the
      clinical aspects for lupus patients. However, some laboratory results became
      abnormal in group 1 patients after the earthquake, indicating that their lupus
      status may have worsened.

PMID- 11958572
TI  - Increased bioactive TNF in human systemic lupus erythematosus: associations with
      cell death.
AB  - In systemic lupus erythematosus (SLE) serum TNF is increased and correlates with
      its soluble receptors and with disease activity. We therefore investigated (i)
      whether the TNF in SLE serum is bioactive, (ii) whether SLE cells react to TNF
      and (iii) whether there are associations with cell death, which is regarded as
      pathogenic in SLE. Sera from active SLE patients induced an increase in
      fibroblast CD54, which was abolished by blocking antibodies against TNF,
      suggesting TNF bioactivity. SLE lymphocytes had a similar surface expression of
      TNF-RI as healthy lymphocytes, their expression of TNF-RII was slightly
      increased. Recombinant TNF induced cell death in PBMC of SLE patients, suggesting
      functional receptors. Serum levels of sTNF-RII (as a surrogate marker for TNF
      activity) correlated with sTNF-RI and disease activity, as expected, and also
      correlated with the percentage of dying lymphocytes and with lymphocytic CD95.
      SLE sera contain increased amounts of biologically active TNF. Peripheral blood
      lymphocytes of SLE patients express functional TNF receptors. Finally,
      associations with cell death and CD95 receptors suggest that TNF may be
      pathogenic in SLE.

PMID- 11958574
TI  - Relationship of tumour necrosis factor alpha gene polymorphisms and
      neuropsychiatric lupus.
AB  - Systemic lupus erythematosus (SLE) is a multisystem disorder which appears to be
      influenced by genetic make-up. In this study we determine allele frequency and
      genotype distribution of TNFalpha polymorphisms in two populations of SLE
      patients (with and without neuropsychiatric manifestations) in order to determine
      whether the rare allele (TNF2) confers susceptibility for neuropsychiatric
      disease in SLE. Patients with SLE were retrospectively reviewed to determine
      presence (n = 17) or absence (n = 47) of documented neuropsychiatric
      manifestations attributable to SLE. The DNA from these patients was extracted
      from peripheral blood mononuclear cells, and PCR amplification, NcoI enzyme
      digestion and 10% polyacrylamide gel electrophoresis were performed to define the
      different TNFalpha alleles. Two alleles were demonstrated, TNF1 (wild-type) and
      TNF2 (rare type), with three possible genotypes, TNF1,1, TNF1,2 and TNF2,2. A
      frequency of 24% was found for the TNF2 patients with neuropsychiatric
      involvement and was not statistically different to a frequency of 28% found in
      SLE patients without neuropsychiatric manifestations. The TNF-2 allele does not
      confer susceptibility for neuropsychiatric manifestations in SLE patients.

PMID- 11958575
TI  - Protein-losing enteropathy in systemic lupus erythematosus: report of a severe,
      persistent case and review of pathophysiology.
AB  - Protein-losing enteropathy (PLE) is a rare manifestation of systemic lupus
      erythematosus (SLE). We report a severe and resistant case of PLE, discuss
      pathophysiology and possible role of cytokines in the disease process. We also
      present a review of the current literature.

PMID- 11958576
TI  - Primary anetoderma associated with primary Sjogren's syndrome.
AB  - We report the case of a woman with a primary Sjogren's syndrome who developed
      asymptomatic anetoderma lesions with no other pathology responsible. This
      dermatosis has been associated with many autoimmune disorders, in particular
      lupus erythematosus and lupus-like syndromes. Our literature review found only
      one previous description of primary anetoderma associated with primary Sjogren's
      syndrome.

PMID- 11958577
TI  - Cyclophosphamide type I hypersensitivity in systemic lupus erythematosus.
AB  - Cyclophosphamide is an important immunosuppressive agent in the treatment of many
      rheumatic diseases. Urticaria and anaphylaxis to intravenous cyclophosphamide
      (i.v. CYC) have been reported in patients with haematological and solid organ
      malignancies. This is the first report in the rheumatology literature of a type I
      hypersensitivity reaction following monthly i.v. CYC. An 18-year-old girl with
      systemic lupus erythematosus (SLE) developed generalized urticaria (without
      concomitant angioedema or anaphylaxis) following i.v. CYC. She had previously
      developed life-threatening angioedema following a respiratory tract infection.
      She successfully completed regular pulse i.v. CYC with pre-medication with anti
      histamine. In the absence of a severe type I hypersensitivity reaction and other
      suitable immunosuppressive agents, i.v. CYC may be safely continued with pre
      medication and careful monitoring during each infusion.

PMID- 11958578
TI  - Antiphospholipid antibodies do not a syndrome make.
AB  - The association of antiphospholipid antibodies (aPLs) with a poor obstetric
      history and/or thrombotic event is typical of the antiphospholipid syndrome
      (APS). We report four cases of poor pregnancy outcome where a diagnostic label of
      APS resulted in delayed recognition of other causes of pregnancy loss. Pregnancy
      outcomes in these women were not improved with antithrombotic therapy alone.
      Successful outcomes were achieved only when other causes of recurrent miscarriage
      were considered and treated.

PMID- 11958579
TI  - Anti-endothelial cell antibodies and biopsy-proven temporal arteritis.

PMID- 11958580
TI  - Warning: thalidomide-related thrombotic risk potentially concerns patients with
      lupus.

PMID- 11958582
TI  - Classes, activity and chronicity indices, and alpha-smooth muscle actin
      expression as prognostic parameters in lupus nephritis outcome.
AB  - Renal biopsies of 86 patients with lupus nephritis were assessed according to the
      WHO classification, and according to activity and chronicity indices. The aim of
      the present study was to correlate clinical, and histological features (WHO
      class, activity and chronicity indices, and alpha-SM actin expression) with the
      progression of lupus nephritis, and identify the pathological role of alpha-SM
      actin in lupus nephritis. The median follow-up time was 75.5 +/- 57.3 months. Two
      patients were grouped as WHO class IIa lupus nephritis, eight patients as class
      IIb, 16 patients as class III, 25 patients as class IV, 15 patients as class V,
      and 19 patients as mixed pattern lupus nephritis. Sex, age, race, and the alpha
      SM actin expression in glomeruli and tubulo-interstitial area in WHO class III
      and IV showed no correlation with clinical follow-up outcome of lupus nephritis.
      Unfavorable clinical outcome of lupus nephritis was correlated with WHO class IV
      compared to the other classes, and with the chronicity index in WHO class III
      patients.

PMID- 11958581
TI  - Antimalarials in cutaneous lupus erythematosus: mechanisms of therapeutic
      benefit.
AB  - Antimalarials are arguably the best modality currently available for treating
      patients with cutaneous lupus erythematosus (LE). Although antimalarials have
      been used for decades in treating cutaneous LE, the precise mechanisms by which
      they provide therapeutic benefit are not well defined. The putative mechanisms by
      which antimalarials might provide therapeutic benefit to patients with cutaneous
      LE include a number of interrelated anti-inflammatory and immunosuppressive
      effects that include photoprotection, lysosomal stabilization, suppression of
      antigen presentation, and inhibition of prostaglandin and cytokine synthesis. If
      we had a more precise understanding of how antimalarials provide therapeutic
      benefit in cutaneous LE we might gain better insight into the pathogenic
      mechanisms of LE and ways of developing better therapies for afflicted patients.

PMID- 11958583
TI  - A Chinese version of the Rheumatology Attitudes Index is a valid and reliable
      measure of learned helplessness in patients with SLE.
AB  - Despite the prognostic importance of learned helplessness (LH) in rheumatic
      diseases, there are no validated measures of LH in Chinese or other Asian
      languages. We therefore assessed the validity of a Chinese translation of the
      Rheumatology Attitudes Index (CRAI; a widely used measure of LH) and its
      Helplessness (CHS) and Internality (CIS) subscales in patients with SLE. Chinese
      speaking SLE patients (n = 69) completed identical, self-administered
      questionnaires containing the CRAI and assessing demographic/socio-economic
      variables twice within 2 weeks. SLE activity, damage and quality of life were
      assessed using the BILAG, SLICC/ACR Damage Index and SF-36 respectively. Scale
      psychometric properties were assessed through Cronbach's alpha, intra-class
      correlations, quantifying test-retest differences, factor analysis and known
      groups construct validity. Internal consistency and reliability were acceptable,
      with Cronbach's alpha for the CHS, CIS and CRAI being 0.70, 0.69 and 0.74,
      respectively. Mean differences in test-retest scores spanned 1.6-2.4% of possible
      scale ranges and intra class correlations ranged from 0.72 to 0.88. Factor
      analysis identified two major factors corresponding to the CHS and CIS subscales
      of the CRAI. Eight of 10 a priori hypotheses relating the CRAI and CHS to
      demographic, disease and quality of life variables were confirmed, supporting the
      construct validity of these scales. The CRAI and its helplessness subscale are
      valid and reliable measures of learned helplessness in Chinese-speaking SLE
      patients.

PMID- 11958584
TI  - Baseline characteristics of a multiethnic lupus cohort: PROFILE.
AB  - PURPOSE: To report the baseline characteristics of a US multi-ethnic, multi
      regional, multi-institution cohort of patients with systemic lupus erythematosus
      (SLE) and how it was constituted. METHODS: Patients with SLE per American college
      of Rheumatology (ACR) classification criteria, 16 years of age and older, with
      disease of 10 years or less, of Hispanic (H), African American (AA) or Caucasian
      (C) ethnicity and living in the geographic catchment areas of the participating
      institutions (the University of Alabama at Birmingham (UAB), Johns Hopkins
      University (JHU), The University of Texas-Houston Health Science Center (UTH)
      were eligible to enter the combined cohort (PROFILE, herein). Data from the
      individual SLE cohorts were pooled and the PROFILE cohort characteristics
      examined using descriptive statistics. Variables predictive of renal damage were
      then examined by logistic regression. RESULTS: The PROFILE cohort constituted by
      568 patients (H = 78, AA = 216, C = 260 (13 other ethnicities)) is predominantly
      female. Non-C had a greater number of ACR criteria, and of renal involvement.
      Among the two non-C groups, a higher proportion of H patients have developed
      overall renal damage, as well as decreased glomerular filtration rate. Other than
      Hispanic ethnicity (odds ratio, OR = 6.27, confidence limits, CL = 1.96-220.01),
      sustained hypertension (OR = 14.16, CL = 4.42-44.33) [corrected] was a
      significant predictor of renal damage, whereas belonging to the JHU cohort was
      protective (OR = 0.18, CL = 0.05-0.63). CONCLUSIONS: We have constituted a large
      US multi-ethnic SLE cohort. Renal involvement was found to be more frequent among
      the non-C; within them, the H patients seem to be at higher risk for the
      occurrence of renal damage.

PMID- 11958585
TI  - Spectrum-analysis and neural networks for imaging to detect and treat prostate
      cancer.
AB  - Conventional B-mode ultrasound currently is the standard means of imaging the
      prostate for guiding prostate biopsies and planning brachytherapy to treat
      prostate cancer. Yet B-mode images do not adequately display cancerous lesions of
      the prostate. Ultrasonic tissue-type imaging based on spectrum analysis of
      radiofrequency (rf) echo signals has shown promise for overcoming the limitations
      of B-mode imaging for visualizing prostate tumors. This method of tissue-type
      imaging utilizes nonlinear classifiers, such as neural networks, to classify
      tissue based on values of spectral parameter and clinical variables. Two- and
      three-dimensional images based on these methods demonstrate potential for guiding
      prostate biopsies and targeting radiotherapy of prostate cancer. Two-dimensional
      images are being generated in real time in ultrasound scanners used for real-time
      biopsy guidance and have been incorporated into commercial dosimetry software
      used for brachytherapy planning. Three-dimensional renderings show promise for
      depicting locations and volumes of cancer foci for disease evaluation to assist
      staging and treatment planning, and potentially for registration or fusion with
      CT images for targeting external-beam radiotherapy.

PMID- 11958586
TI  - Compounding for a forward-viewing ring-annular ultrasound array system.
AB  - The 3-D data set from a forward-viewing ring-annular array opens up opportunities
      for compounding in both axial and lateral directions. To explore this potential,
      we performed a simulation study analyzing 3-D ultrasound data from various
      phantoms. For a vessel phantom, our results indicate compounding could boost
      contrast to noise ratio (CNR) (up to a factor of 4 in our results) without
      significant compromise in in-plane image resolution. For an isotropic cyst
      phantom, axial and lateral compounding performs similarly. Such improvement
      should be helpful for device guidance with IVUS (Intravascular Ultrasound) in
      interventional procedures.

PMID- 11958587
TI  - Blood flow estimation with harmonic Flash Echo Imaging.
AB  - Blood volume flow estimation remains an important task for the functional
      evaluation of internal organs. In vitro and in vivo flow estimation has been
      carried out using Flash Echo Imaging in harmonic mode after the administration of
      microbubble-based ultrasound contrast agents. The in vitro flow volume rate
      correlated with the constant replenishment level but less so with the video
      intensity decay rate. The in vivo volume flow rates obtained in four dogs agreed
      well with CVI-Q (time domain correlation) based flow measurement. Our
      experimental results indicate that the volume flow rate can be accurately
      estimated in vitro and in vivo using harmonic Flash Echo imaging.

PMID- 11958588
TI  - CD28 function: a balance of costimulatory and regulatory signals.
AB  - Both the recognition of MHC/antigen complex by the T-cell receptor and engagement
      of costimulatory molecules are necessary for efficient T-cell activation. CD28
      has been widely recognized as the major costimulation pathway for naive T-cell
      activation, and the CD28/B7 pathway plays a central role in immune responses
      against pathogens, autoimmune diseases, and graft rejection. In this review, we
      will summarize evidence that CD28 is also prominent in the regulation of immune
      responses and the maintenance of peripheral tolerance. Indeed, CD28 engagement
      increases the expression of the down-modulatory molecule CTLA-4, induces the
      differentiation of Th2 cells that have a protective function in autoimmunity, and
      has an obligatory role in the homeostasis of regulatory T cells. Therefore,
      CD28/B7 interactions induce a balance of costimulatory and regulatory signals
      that have opposite outcomes on immune responses. This new perspective on CD28
      function suggests that caution should be taken in the development of
      immunotherapies targeting costimulatory pathways.

PMID- 11958589
TI  - Assessment of safety and the immune response to the CD4 "internal antigen" mouse
      anti-idiotypic Mab 16D7 in four patients with SLE.
AB  - We have analyzed the immune response elicited with the human CD4 internal antigen
      anti-idiotypic monoclonal antibody 16D7 in four patients with active systemic
      lupus erythematosus and assessed the safety of the treatment. Patients I and 2
      received three 2-mg 16D7 subcutaneous (SC) injections at 3-week intervals and
      mainly developed IgGI, whereas IgG1, IgG3, and IgG4 were detected in the sera of
      the other two patients (3 and 4) who received the same amount of 16D7 on days 0,
      28, and 70. 16D7-F(ab')2 isotypic determinant-specific antibodies levels,
      evaluated by sera reactivity with the 16D7-isotype matched anti-idiotypic
      monoclonal antibody 14D6-F(ab')2, were low or undetectable in patient 1 and
      became detectable following the first and second boosters in patient 3 and
      patients 2 and 4, respectively. The highest level was seen in patients 3 and 4.
      The focusing pattern (spectrotype) of 16D7 idiotypic-specific antibodies
      suggested that multiple V genes are involved or many somatic mutations occur.
      Once established, each patient's spectrotype remained stable. Although
      spectrotype were individually distinct, all four patients produced CD4-specific
      antibodies, indicating that this response crosses the genetic barrier. Disease
      relapsed after 11 (patient 2), 40 (patients 3 and 4), and 125 (patient 1) weeks.
      The lack of side effects and the prolonged periods of disease control (33 and 103
      weeks after the last booster) warrants an extension of this study.

PMID- 11958590
TI  - Cervical concentrations of interleukin-10 and interleukin-12 do not correlate
      with plasma levels.
AB  - Human papillomavirus (HPV) infects the transformation zone of the cervix and is
      the primary cause of cervical cancer. The infection is localized to the cervix
      and mucosal immunity is likely to be an important determinant for viral
      clearance. Previous studies of immunity to HPV have measured immune markers in
      the blood, but the relationship of systemic immunity to cervical immunity is
      poorly understood. In this study of 70 women enrolled in the ASCUS-LSIL Triage
      Study (ALTS), a clinical trial for management of low-grade cytologic
      abnormalities of the cervix, we collected paired plasma and cervical secretions
      to investigate the relationship between cervical concentrations of interleukin-10
      (IL-10) and interleukin-12 (IL-12) and plasma levels. Neither IL-10 (p = 0.11),
      or IL-12 (p = -0.04) nor the ratio of IL-12 to IL-10 (p = 0.06) were correlated
      between blood and cervical secretions. Except for weak correlations of IL-10
      among nonsmokers (p = 0.35. P = 0.019) and those in day 18-27 of their menstrual
      cycle (p = 0.51, P = 0.015), this lack of correlation persisted in all subgroups
      defined by genital inflammation or infection, current oral contraceptive use,
      heme contamination and volume of collected secretions, HPV16 seropositivity, and
      repeat HPV infection and/or cytologic abnormalities. The lack of correlation and
      high concentrations in cervical secretions indicate that the cervical IL-10 and
      IL-12 concentrations exceed what could be expected from blood as a principle
      source of IL-10 and IL-12 and suggest that cytokine concentrations in cervical
      secretions are predominantly the result of local cytokine production.

PMID- 11958591
TI  - HLA-Cw7 zygosity affects the size of a subset of CD158b+ natural killer cells.
AB  - Individuals with certain HLA class I genotypes are highly susceptible to disease
      after viral infection. Natural killer (NK) cells kill virus-infected cells
      through a mechanism involving HLA class I receptors. These facts may be connected
      if an individual's HLA genotype regulates the number and function of NK cells. We
      have observed that subjects homozygous for the HLA-B/C region of conserved major
      histocompatibility complex (MHC) extended haplotypes have lower NK cell activity
      and a significantly lower frequency of CD16+CD56+ NK cells than heterozygotes.
      The proportion of CD16-CD56+ NK cells was unaffected by zygosity for the HLA-B/C
      region. We show here that the frequency of CD16+CD158b+, but not CD16-CD158b+ NK
      cells, was significantly lower (p <0.026) in homozygotes for HLA-Cw7 (NKI ligand)
      haplotypes than in heterozygotes. The frequencies of CD16+CD158a+ and CD16
      CD158a+ and CD16-CD158a+ or CD16+NKB1+ and CD16-NKB1+ NK cells were not different
      in these donor groups. These findings suggest that the proportion of NK cells
      coexpressing CD16 and CD158b, but not CD158a nor NKB1, is influenced by zygosity
      for the HLA-Cw7 (NK1 ligand) haplotype. Since NK cells are involved in protection
      from virus infection, a reduced size of a ligand-specific NK subset in
      individuals homozygous for some HLA-B/C haplotypes may help explain their
      increased susceptibility to virus-induced diseases.

PMID- 11958594
TI  - "Alternatives" search: is it effective?-- Letter to editor and challenge to YOU.

PMID- 11958593
TI  - The case definition of chronic fatigue syndrome.
AB  - The 1994 case definition of chronic fatigue syndrome is widely used not only for
      diagnosis but also for clinical and laboratory-based observations of this
      clinical entity. The criteria for the 1994 case definition are based primarily on
      symptoms and not on physical signs or chemical or immunological tests. This
      situation has resulted in conflicting clinical and laboratory observations that
      in all likelihood is due to different populations of patients being studied in
      different centers. Based on some of the recent publications, there appears to be
      an emerging picture of this disease entity that we propose could be used to
      subgroup chronic fatigue syndrome into four different subclasses. These
      subclasses would consist of chronic fatigue with primarily nervous system
      disorders such as impaired memory or concentration and headache, chronic fatigue
      with primarily endocrine system disorders such as unrefreshing sleep and
      postexertional malaise, chronic fatigue with musculoskeletal system disorders
      such as muscle pain and joint pain, and chronic fatigue with immune
      system/infectious disorders such as sore throat and tender lymph nodes. It is
      suggested that if clinical and laboratory-based studies on chronic fatigue
      syndrome were conducted on more homogeneous subgroups of patients, the data from
      one center to the other might not be as conflicting and more insights can be shed
      on the nature of this clinical condition.

PMID- 11958595
TI  - Electronic protocol review system--reply from the authors.

PMID- 11958596
TI  - Reduction and refinement--what efforts are truly effective?

PMID- 11958592
TI  - Rifampicin inhibits CD95-mediated apoptosis of Jurkat T cells via glucocorticoid
      receptors by modifying the expression of molecules regulating apoptosis.
AB  - Rifampicin and its analogues are increasingly used in the treatment and
      prophylaxis of mycobacterial infections. Recently, it has been demonstrated that
      rifampicin binds to and activates glucocorticoid receptors (GR). Glucocorticoids
      may inhibit or promote apoptosis in various cell types. Therefore, we
      investigated the effect of rifampicin on anti-CD95-induced apoptosis in Jurkat T
      cells. Rifampicin, in a concentration-dependent manner, inhibited anti-CD95
      induced apoptosis. Furthermore, rifampicin down-regulated the expression of Bax
      and CD95L and up-regulated the expression of Bcl-2, Bcl-xL, and Flice-inhibitory
      protein-L (FLIPL); however, rifampicin had no effect on CD95 or XIAP expression.
      Rifampicin did not inhibit the binding of anti-CD95 monoclonal antibody to CD95
      receptor. A GR-specific antagonist RU480 reversed the inhibition of apoptosis by
      rifampicin. Furthermore, rifampicin failed to inhibit anti-CD95-induced apoptosis
      in a dominant negative IKBalpha (IKBaM) Jurkat T cells. Taken together, these
      findings suggest that rifampicin inhibits anti-CD95-induced apoptosis in Jurkat T
      cells by modulating the expression of various molecules regulating apoptosis and
      its effect appears to be mediated via GR and at least in part through NF-kappaB
      signaling pathway.

PMID- 11958597
TI  - Atmospheric waste isoflurane concentrations using conventional equipment and rat
      anesthesia protocols.
AB  - Chronic, low-level exposure of health care professionals to waste anesthetic
      gases has been linked to increased incidences of neurologic and reproductive
      dysfunction, hepatic and renal toxicity, and neoplasia. The present study
      assessed the potential for waste anesthetic gas exposure to researchers
      administering isoflurane to rats by using standard delivery systems and
      conventional anesthesia protocols. Well-maintained bench-top precision isoflurane
      vaporizers were equipped with two circuits (a nonrebreathing one hooked to a
      modified Bain facemask, and the other to an induction box) attached to
      commercially available, activated charcoal canisters (passive gas scavenging).
      The isoflurane concentration was varied from 1% to 5%, while the oxygen flow rate
      was either 1 or 2.5 L/min. Real-time atmospheric isoflurane levels were assessed
      by using a portable infrared spectrophotometer. When euthanized female sentinel
      CD rats were positioned in the facemask loop, isoflurane emissions at the mask
      rat interface, breathing zone, and exhaust port of scavenging canisters were
      increased in proportion to the isoflurane concentration and oxygen flow rates as
      well as the amount of gas directed through the facemask circuit. Isoflurane was
      detected in the anesthetist s breathing zone only if the entire carrier gas flow
      was directed to the facemask loop. The background isoflurane level rose to 0.5
      ppm after 75 min of continuous bench-top operation in a room with 22 air
      exchanges hourly but did not escalate if the anesthesia unit--or at least the gas
      scavenging canister--was placed in a fume hood, or if the system was used in a
      room with 42 hourly air changes. Isoflurane efflux via the exhaust ports exceeded
      5 ppm in 31% of gas-scavenging canisters that had not reached their maximum use
      life (as defined by the manufacturer's specifications); in a parallel prospective
      study, isoflurane was emitted from 88% of canisters by the time that they had
      reached 50% of their specified lifespan. These data indicate that (1) isoflurane
      emissions likely will occur at trace levels in laboratory animal facilities even
      when well-maintained precision isoflurane vaporizers equipped with conventional
      activated charcoal (passive) gas-scavenging units are used and (2) exposure to
      anesthetic pollution can be mitigated substantially by selecting low-flow
      anesthesia regimens, improving gas-scavenging practices, and optimizing the
      configurations of the delivery system and work area.

PMID- 11958598
TI  - Strain variation of immature female rats in response to various superovulatory
      hormone preparations and routes of administration.
AB  - The purpose of this study was to examine the response of rats of different
      genetic backgrounds to various superovulatory hormonal treatments. Immature
      Sprague Dawley (SD), FBNF1, and F344 female rats (30 to 35 days of age) were used
      for this study as representatives of outbred, hybrid, and inbred strains
      respectively. Animals from each strain were allocated into four groups of hormone
      treatments as follows: 1) 30 IU pregnant mare serum gonadotrophin (PMSG)
      intraperitoneally (i.p.) followed 52 h later with 25 IU human chorionic
      gonadotrophin (HCG) i.p.; 2) 15 IU PMSG i.p. followed 52 h later with 7.5 IU HCG
      i.p.; 3) 1.0 IU follicle stimulating hormone (FSH) daily via Alzet mini-pumps for
      60 h; and 4) 1.0 IU FSH daily via Alzet mini-pumps for 54 h followed by 10 mg
      luteinizing hormone (LH). The efficacies of the hormone treatments were evaluated
      using the following criteria: % mated, % ovulated, total oocytes per female, and
      % fertilized. The % mated of SD rats treated with PMSG(30)+HCG(25) was
      significantly higher (P < 0.05) than that of animals treated with
      PMSG(15)+HCG(7.5); in addition, the total oocytes per female was significantly
      higher (P < 0.05) for SD animals receiving PMSG(30)+HCG(25) than all other
      treatments. The % ovulated of SD rats was significantly lower (P < 0.05) in
      response to FSH alone as compared to all other treatments. The % ovulated for
      FBNF1 rats was significantly greater (P < 0.05) in response to both PMSG+HCG
      treatments as compared to FSH and FSH+LH. The % ovulated and % fertilized were
      significantly lower (P < 0.05) in F344 rats treated with FSH alone as compared to
      all other treatments. F344 rats produced significantly (P < 0.05) more oocytes
      per female in response to both PMSG+HCG treatments as compared to FSH and FHS+LH.
      The % ovulated of SD and F344 rats were significantly higher (P < 0.05) than that
      of FBNF1 rats in response to FSH and FSH+LH. SD rats produced a significantly
      greater (P < 0.05) number of oocytes per female than did FBNF1 rats in response
      to PMSG(30)+HCG(25) and a significantly greater (P < 0.05) number of oocytes per
      female as compared to those of FBNF1 and F344 rats in response to FSH and FSH+LH.
      The % fertilized of SD and FBNF1 rats were significantly higher (P < 0.05) than
      that of F344 rats in response to PMSG(15)+HCG(7.5). Our study demonstrates that
      treatment with PMSG+HCG is an effective method of eliciting superovulatory
      responses according to most criteria examined. We have also shown that outbred
      (SD) rats generally produced more oocytes per female in response to hormonal
      stimulation than did inbred and hybrid rats. Our results indicate that different
      strains of rats have various degrees of hormone sensitivity and response to
      different superovulation protocols.

PMID- 11958599
TI  - Determination of a humane endpoint in the L1210 model of murine leukemia.
AB  - The purpose of our study was to derive an alternate end-point to death or
      moribund appearance for the frequently used L1210 model of murine leukemia. In
      reviewing the published literature, we were unable to identify a suitable
      intermediate marker of substantive disease that predicted outcome in the BDF1
      recipient of the L1210 leukemia. In an attempt to refine the use of animals in
      our laboratory, we developed a scoring sheet for behavioral and physical changes
      that followed intravenous injection of L1210 lymphocytic leukemia cells into BDF1
      recipients. At 12-h intervals for the first 2 days after tumor-cell injection and
      at 6-h intervals thereafter, animals were observed and scored for each parameter.
      When death was imminent, animals were euthanized by inhalation of methoxyflurane
      followed by decapitation. Changes in physical and behavioral characteristics then
      were correlated with the end-point of death. Changes occurred in the mice
      approximately 7 days after tumor cell inoculation and 24 h before death. The
      earliest of these signs was hunched posture, followed by one or more other
      characteristics including decreased activity, increased facial swelling, ears in
      backward position, abdominal swelling, squinting eyes, and labored breathing.
      From these data, we were able to develop criteria for early euthanasia. Use of
      these intermediate end-points likely will substantially reduce the stress on the
      animals without compromising scientific outcomes in experiments using this or
      related preclinical models of cancer.

PMID- 11958601
TI  - The RAG 2 mouse model for xenografted human oral squamous cell carcinoma.
AB  - Animal tumor models are still essential for the development of new medication and
      therapy concepts. In the field of human oral squamous cell cancer, there are few
      reliable xenografted tumor models available. Therefore, during a two-course
      experiment, we established a new xenografted tumor model of human oral squamous
      cell cancer. The tumor growth rates of two different tumor cell lines were
      compared in the inbred immunodeficient CD-17-RAG 2 mouse, NMRI-SCID mouse
      (scid/scid), and Swiss nude mouse (nu/nu). The tumor cell line from a lymphnode
      metastasis of an oral squamous cell carcinoma (XF 354) had a faster growth rate
      and a more characteristic histology than did the cell line from the primary tumor
      of a squamous cell carcinoma of the floor of the mouth (UM-SCC-14C). The highest
      tumor growth rate was observed in the RAG 2 mouse, followed by the SCID mouse.
      The Swiss nude mouse showed no tumor growth. The combination of the XF 354 tumor
      cell line and the RAG 2 mouse was most successful, with a tumor growth rate of
      95%. Our animal model is very reliable and allows manipulations for as long as 30
      min under anesthesia outside of microbiologic safety cabinets, where the handling
      of animals is much more comfortable and less time-consuming. The tumor histology
      was easily interpreted by using light microscopy. Steps for cell cultivation and
      tumor implantation are described and discussed. Therefore we strongly recommend
      the use of the model comprising the RAG 2 mouse with the xenografted cell line XF
      354 for research in the field of human oral squamous cell carcinoma.

PMID- 11958600
TI  - Operative technique for safe pulmonary lobectomy in Sprague-Dawley rats.
AB  - To perform safe and effective animal surgery, it is essential to follow a well-
      disciplined approach. We recently have embarked on a variety of wound-healing
      studies that involve multiple operative techniques including thoracotomy with
      lobectomy. Such procedures require specific attention to effective anesthesia and
      ventilation as well as a structured and safe approach to the actual procedure. We
      have developed operative techniques for thoracotomy and pulmonary lobectomy that
      limit animal morbidity and mortality. Using general anesthesia, we safely and
      effectively completed right thoracotomy and pulmonary lobectomy in 51 of the 54
      (>94%) of the Sprague-Dawley rats that were our subjects. We effectively
      ventilated the animals with inhalation anesthesia, avoiding the need for
      endotracheal intubation. The three mortalities occurred during early experiments
      and were attributable to easily identified technical errors. Our animals did not
      experience postoperative respiratory complications. Postoperative recovery was
      excellent, and no appreciable postoperative morbidity was encountered.

PMID- 11958602
TI  - A review of treatments for the eradication of pinworm infections from laboratory
      rodent colonies.
AB  - Oxyurids are common contaminants of both specific pathogen-free and conventional
      rodent colonies. This paper reviews the biology and life cycles of oxyurid
      parasites of laboratory rodents, mechanisms of action and potential adverse
      effects of commonly used treatments, and treatment modalities, both historical
      and recent.

PMID- 11958603
TI  - A comparison of body temperature changes due to the administration of ketamine
      acepromazine and tiletamine-zolazepam anesthetics in cynomolgus macaques.
AB  - Two commonly used anesthetic combinations, ketamine acepromazine and tiletamine
      zolazepam, were compared to identify their effects upon body temperature in
      cynomolgus macaques. We allocated 30 cynomolgus macaques previously implanted
      with subcutaneous telemetry devices into two groups of 15 animals. Baseline
      temperature data were collected for 3 days before administering anesthesia to
      establish normal diurnal temperature patterns for each monkey. Each group then
      was anesthetized with either ketamine-acepromazine or tiletamine-zolazepam, and
      their body temperatures were recorded at 15-min intervals. Both groups had marked
      decreases in body temperature, with the greatest decreases in the tiletamine
      zolazepam group. In addition, both groups had notable post-anesthesia elevations
      in body temperature that often lasted for more than 24 h postinduction.

PMID- 11958604
TI  - The use of fecal markers to facilitate sample collection in group-housed cats.
AB  - The provision of proper social housing is a priority when designing an experiment
      using domestic cats as laboratory animals. When animals are group-housed, studies
      requiring analysis of stool samples from individual subjects pose difficulty in
      sample collection and identification. In this study, commercially available
      concentrated food colorings (known as bakers  pastes) were used as fecal markers
      in group-housed cats. Cats readily consumed 0.5 ml of bakers  paste food coloring
      once daily in canned cat food. Colorings served as fecal markers by imparting a
      distinct color to each cat s feces, allowing identification in the litter box. In
      addition, colored glitter (1/8 teaspoon in canned food) was fed to cats and found
      to be a reliable fecal marker. Long-term feeding of colorings and glitter was
      found to be safe and effective at yielding readily identifiable stools.

PMID- 11958605
TI  - Horizontal transmission of recombinant vaccinia virus in strain 13 guinea pigs.
AB  - At our research facility, guinea pigs subcutaneously inoculated with recombinant
      vaccinia viruses traditionally are isolated from other research animals because
      of the assumption that viral shedding and transmission may occur postvaccination.
      However, an extensive literature search failed to reveal any information
      supporting this assumption. The purpose of this study was to determine whether
      horizontal transmission of recombinant vaccinia virus vaccines occurs
      postinoculation in strain 13 guinea pigs and to what degree. We scheduled 12
      strain 13 guinea pigs for three subcutaneous inoculations with 10(7) PFU
      recombinant vaccinia virus at 3- to 4-week intervals. An additional 36
      unvaccinated or naive strain 13 guinea pigs were either cohoused with these
      vaccinees, housed in cages directly below the vaccinated guinea pigs, or placed
      in cages located across, and downwind (relative to room airflow), from vaccinees.
      Pre- and postvaccination serum samples were analyzed for the presence of vaccinia
      specific antibodies by enzyme-linked immunosorbent assay. All 36 of the
      unvaccinated guinea pigs tested negative for antibodies to the vaccinia virus at
      all time points. The absence of virus-specific antibodies in the nonvaccinated
      guinea pigs, whereas vaccinated animals seroconverted, suggests that horizontal
      transmission of recombinant vaccinia virus does not occur between strain 13
      guinea pigs housed in the same study room, regardless of cage location.

PMID- 11958606
TI  - Pulmonary masses in a tuberculin skin test-negative olive baboon.
AB  - An adult female olive baboon was shipped to the University of Illinois at Chicago
      (UIC) from another institution and placed in quarantine. This baboon had been
      wild-caught approximately 1 year earlier. Initial quarantine examination at UIC
      revealed tachypnea and an elevated white blood cell count. Intradermal tests for
      tuberculosis were negative. Radiographs demonstrated increased density, three
      radiopaque masses in the lung fields,and hepatosplenomegaly. Each differential
      diagnosis considered had a poor prognosis, and the animal was euthanized and a
      necropsy performed. At necropsy, five intact cysts in the liver and two in the
      lungs were identified. In addition, the right apical lung lobe was collapsed,
      contained an apparently old, ruptured cyst, and had numerous fibrous adhesions to
      the thoracic wall. Microscopic examination of the cysts and cyst-fluid revealed
      that the cysts were multilaminated structures that contained viable Echinococcus
      granulosus protoscolices; therefore a diagnosis of hydatidosis was made. Recent
      advances in tests used to screen humans for hydatidosis have led to the
      development of an immunoblot and enzyme immunoassay, which are highly sensitive
      and specific. In this report, we verified the usefulness of these tests for
      detecting hydatidosis in baboons. Serum from the infected baboon and from three
      other apparently healthy members of the colony were sent to the Centers for
      Disease Control and Prevention to be tested. Serum from the infected baboon
      yielded positive results in both the immunoblot and enzyme immunoassay, whereas
      tests on serum from the normal baboons were negative. Therefore, both the
      immunoblot and enzyme immunoassay represent potentially valuable tools for
      diagnosing hydatidosis in nonhuman primates.

PMID- 11958607
TI  - Development of an enzymatic method to quantify methyl ketones from bacterial
      origin.
AB  - Methyl ketones are detected in dry fermented sausages in which they contribute to
      the cured aroma. They have been associated with the inoculation of Staphylococcus
      carnosus used as starter culture. To evaluate the ability of bacterial starters
      to produce methyl ketones it was necessary to develop a rapid method. The method
      consists of a reaction catalyzed by a commercial NADPH-dependent alcohol
      dehydrogenase that reduces the 2-pentanone to its secondary alcohol. The
      linearity, the specificity, and the robustness were studied. Its accuracy was
      confirmed by comparison with the gas chromatography technique. Finally, the
      method was validated on biological samples such as the 2-pentanone produced by
      Staphylococcus carnosus. The enzymatic method offers some advantages over the gas
      chromatography, as it is faster, simpler, and inexpensive, guaranteeing an
      effective way to assess bacterial ketone production.

PMID- 11958608
TI  - High-resolution nuclear magnetic resonance spectroscopy and multivariate analysis
      for the characterization of beer.
AB  - Beer contains a very complex mixture of nutrients, which in this work are
      identified to some extent by high-field high-resolution nuclear magnetic
      resonance (NMR) one- and two-dimensional methods. The (1)H NMR spectrum of beer
      shows a predominance of strongly overlapped peaks arising from several
      carbohydrates. Minor components are clearly observed both in the aliphatic and in
      the aromatic regions of the spectrum. With the aid of two-dimensional methods,
      spectral assignment was carried out, enabling the identification of approximately
      30 compounds and identifying about the same number of spin systems for further
      assignment. The variability of the spectral profile of beers differing in type
      and label was studied by principal component analysis (PCA), and it was found
      that, although some distinction is achieved on the basis of the aliphatic and
      sugar compositions, clearer separation between ales and lagers is obtained by PCA
      of the aromatic profiles alone. The potential of this technique as a rapid and
      informative quality control tool is discussed.

PMID- 11958609
TI  - On-line HPLC-DPPH screening method for evaluation of radical scavenging phenols
      extracted from apples (Malus domestica L.).
AB  - An on-line HPLC-DPPH screening method for phenolic antioxidants in apple
      methanol/water (80:20, v/v) extracts was applied. The determination of
      antioxidants was based on a decrease in absorbance at 515 nm after postcolumn
      reaction of HPLC-separated antioxidants with the 2,2'-diphenyl-1-picrylhydrazyl
      radicals (DPPH*). Each of the antioxidants separated by the HPLC column was
      observed as a negative peak corresponding to its antioxidative activity. The on
      line method was applied for quantitative analysis of the antioxidants. A linear
      dependence of negative peak area on concentration of the reference antioxidants
      was observed. For validation of the on-line method the limit of detection, LOD
      (microg/mL), and the limit of quantification, LOQ (microg/mL), of the phenolic
      compounds were determined. Comparison of the UV and DPPH radical quenching
      chromatograms with authentic compounds identified catechin, chlorogenic acid,
      caffeic acid, epicatechin, and phloridzin in the apple cultivars (Lobo, Golden
      Delicious, and Boskoop), and the distribution of total antioxidant activity was
      calculated.

PMID- 11958610
TI  - Antioxidant functions of selected allium thiosulfinates and S-alk(en)yl-L
      cysteine sulfoxides.
AB  - Pure thiosulfinates, R-S(O)S-R (2), where R = Me (2a), Pr (2b), or All (2c), at
      levels up to 4 mM were not capable of scavenging hydrogen peroxide or superoxide
      anion. Relative to standard antioxidants (ascorbic acid, n-propyl gallate,
      butylated hydroxytoluene, Trolox, and reduced glutathione), these thiosulfinates
      were 1-3 orders of magnitude less efficient at reducing 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical, 0.5-2 orders of magnitude less efficient at
      quenching singlet oxygen, and about equally effective at scavenging hydroxyl
      radical. Generally, AllS(O)SAll (2c) was the most effective and PrS(O)SPr (2b)
      was the least effective thiosulfinate in these assays, except that MeS(O)SMe (2a)
      exhibited no quenching effect toward singlet oxygen. These thiosulfinates were
      also incapable at levels up to 0.1 mM (where they were toxic) of in vitro
      induction of quinone reductase (QR) in murine hepatoma (hepa 1c1c7) cells.
      However, S-1-propenyl-L-cysteine sulfoxide (isoalliin, 1a) and cycloalliin (3)
      induced QR in this system at 2 mM and 1 mM, respectively, although doubling of QR
      required levels of 10-15 mM.

PMID- 11958611
TI  - Concentration levels of zearalenone and its metabolites in urine, muscle tissue,
      and liver samples of pigs fed with mycotoxin-contaminated oats.
AB  - The content of zearalenone and its metabolites in urine and tissue samples from
      pigs fed zearalenone-contaminated oats was established by analytical methods
      combining solid-phase extraction cleanup of the samples with highly selective
      liquid chromatography-mass spectrometry (LC-MS)/MS detection. Investigation of
      the urine samples revealed that approximately 60% of zearalenone was transformed
      in vivo to alpha-zearalenol and its epimer beta-zearalenol in a mean ratio of
      3:1. Zeranol and taleranol as further metabolites could only be detected in trace
      amounts. Zearalanone was identified at considerable concentrations, though only
      in a couple of samples. In contrast, liver samples contained predominantly alpha
      zearalenol, and to a minor extent beta-zearalenol and zearalenone, with a mean
      ratio of alpha-/beta-zearalenol of 2.5:1, while zeranol, taleranol, or
      zearalanone could not be identified in any of the investigated samples. The
      degree of glucoronidation was established for zearalenone as 27% in urine and 62%
      in liver; for alpha-zearalenol as 88% in urine and 77% in liver; and for beta
      zearalenol as 94% in urine and 29% in liver. Analyses of muscle tissue revealed
      relatively high amounts of nonglucuronidated zeranol and alpha-zearalenol
      together with traces of taleranol and zearalenone, indicating that the metabolism
      of zearalenone and its metabolites is not restricted to hepatic and
      gastrointestinal metabolic pathways.

PMID- 11958612
TI  - Botanical origin and chemical composition of Brazilian propolis.
AB  - Brazilian propolis has been classified into 12 groups based on physicochemical
      characteristics: five in the southern Brazil group (group 3), one in the
      southeastern Brazil group (group 12), and six in the northeastern Brazil group
      (group 6). The plant origins of these groups were investigated using reversed
      phase high-performance thin-layer chromatography (RPHPTLC), reversed-phase high
      performance liquid chromatography (RPHPLC), and gas chromatography-mass
      spectrometry (GC-MS). It was concluded that the origins of propolis group 3,
      group 6, and group 12 are resins of the poplar tree, Hyptis divaricata, and
      Baccharis dracunculifolia, respectively.

PMID- 11958613
TI  - Biodiversity of mannose-specific lectins within Narcissus species.
AB  - Mannose-specific lectins (MSLs) were isolated from the bulbs of 27 species of
      wild Spanish Narcissi and compared to the commercially available MSL from
      daffodil (Narcissus pseudonarcissus, NPA). Molecular weight analysis showed the
      monomers of all the MSLs were at, or around, 12.5 kD. Haemagglutination assays
      showed that the MSLs exhibited activities at up to four times greater than that
      displayed by NPA and other MSLs derived from other species such as Galanthus
      nivalus (snowdrop) and Allium ursinum (ramson). Elution profiles from ion
      exchange chromatography exhibited similarities for species within the same
      taxonomic section suggesting that this method could aid in species
      classification. Further analysis by isoelectric focusing showed many isolectins
      are present in vivo and that even within a single peak from ion exchange
      chromatography there are numerous isolectins present. The basis of the isolectin
      heterogeneity is suggested to reside in the tetraploidy (sometime triploidy)
      nature of Narcissus genes.

PMID- 11958614
TI  - Changes in the concentrations of bioactive compounds in plantain leaves.
AB  - The plantain is used in herbal medicines and for pasturage. Two cultivars of
      plantain (Plantago lanceolata L.), Grasslands Lancelot and Ceres Tonic, were sown
      in spring. Changes in catalpol, aucubin, and acteoside concentrations in the
      leaves during the growing season and by drying after harvesting were
      quantitatively determined by high-performance liquid chromatography. The
      concentration of catalpol was relatively low, fluctuating between 1 and 2% of dry
      matter during the growing season, and there was no clear-cut seasonal change.
      From spring to midfall, the aucubin concentration increased from 2.1 to 4.8% in
      Grasslands Lancelot and from 1.0 to 2.7% in Ceres Tonic. These increases were
      gradual over the season, except for during midsummer, when aucubin concentrations
      were relatively constant. The acteoside concentration increased from 3.4 to 7.1%
      in Grasslands Lancelot and from 1.5 to 4.1% in Ceres Tonic over the course of the
      growing season, although in the summer it declined steadily to lows of 2.5% in
      Grasslands Lancelot and 1.9% in Ceres Tonic. Our data suggested that midfall was
      the appropriate time for harvesting plantain for medicinal use. The
      concentrations of the bioactive compounds steadily decreased in the initial
      stages of drying both under natural climatic conditions and at 60 degrees C. The
      development of processing methods to minimize the loss of bioactive compounds is
      imperative.

PMID- 11958615
TI  - Characterization, quantification, and bioactivities of anthocyanins in Cornus
      species.
AB  - Cornus mas, Cornus officinalis, Cornus controversa, and Cornus kousa (Cornaceae)
      bear edible fruits that are consumed in parts of Europe and Asia. This study
      undertook the investigation of the presence and levels of anthocyanins in the
      fruits of these Cornus species by HPLC. The anthocyanins present in Cornelian
      cherries, C. mas, are delphinidin 3-O-beta-galactopyranoside (1), cyanidin 3-O
      beta-galactopyranoside (2), and pelargonidin 3-O-beta-galactopyranoside (3). C.
      officinalis contains only anthocyanins 1-3, similar to C. mas, but in different
      proportions. However, C. controversa contains anthocyanins 1-3 among other
      anthocyanins, but Chinese dogwood, C. kousa, did not contain 1-3. The contents of
      pure anthocyanins 1, 2, and 3 in 1 kg of fresh fruits of C. mas, C. officinalis,
      and C. controversa were 280, 1079, and 710 ppm; 11, 77, and 230 ppm; and 600,
      1000, and 700 ppm, respectively. In cyclooxygenase (COX)-I and -II enzyme
      inhibitory assays, anthocyanins 1-3 (all 40 microM) showed activities of 9.2 and
      11.7%; 7.6 and 12.4%; and 5.3 and 7.8%, respectively, compared to Naproxen (54.3
      and 41.3%; 10 microM), ibuprofen (47.5 and 39.8%; 10 microM), Celebrex (46.2 and
      66.3%; 1.67 ppm), and Vioxx (23.8 and 88.1%, 1.67 ppm). In the antioxidant assay,
      anthocyanins 1-3 (all 40 microM) showed activities of 70.2, 60.1, and 40.3%,
      respectively. At 10 microM concentration, commercial synthetic antioxidants tert
      butylhydroquinone, butylated hydroxytoluene, butylated hydroxyanisole, and
      vitamin E gave 83.2, 79.7, 82.1, and 10.2% of antioxidant activity, respectively.

PMID- 11958616
TI  - Structural identification of new curcumin dimers and their contribution to the
      antioxidant mechanism of curcumin.
AB  - As a part of the research project on the elucidation of the chain-breaking
      antioxidant mechanism of natural phenolics against the oxidation of food
      components, curcumin, a main turmeric pigment, was investigated. A relatively
      high concentration of curcumin gave three dimers as radical termination products
      in addition to the coupling products with curcumin and the lipid hydroperoxide.
      The structural analysis of these dimers and quantitative analysis of their
      production rates revealed that radical-radical termination mainly occurred at the
      2-position of curcumin. The contribution of the pathway for production of these
      dimers to the antioxidant mechanism of curcumin was estimated from the
      concentration-dependent data of the antioxidant activity and formation rates of
      these termination products. The A-A termination (dimer formation) was estimated
      to contribute at least about 40% of the entire antioxidant process against ethyl
      linoleate oxidation.

PMID- 11958617
TI  - Isolation and characterization of lactic acid bacteria from feces of newborn baby
      and from dongchimi.
AB  - Lactic acid bacteria were screened from feces of newborn baby and from dongchimi.
      Selection criteria employed included the ability of strains to withstand
      environmental conditions such as low pH, high bile concentration, and oxygen. The
      isolates were applied to the juice of various vegetables, and fermentabilities of
      isolates were compared. Strains F20-3, F35-3, and F35-6 showed high stability
      compared to the other strains at pH 3.0 and 2.3. Strains D1 and D2 showed the
      highest survival at pH 3.0 and survived at 1% high bile concentration. The
      selected strains were able to survive at low pH and relatively high bile
      concentration and were not affected by oxygen. The growth of isolates was >10(7)
      cfu/mL in natural media, and strains were not affected by the pH values of the
      vegetables. Therefore, isolated strains are thought to survive through the
      intestinal ecosystem and are considered to be suitable for application of the
      fermented product using various vegetables for their functionality. The isolates
      were identified as Lactobacillus plantarum and Lactobacillus fermentum.

PMID- 11958618
TI  - Biodegradation of viticulture wastes by Pleurotus: a source of microbial and
      human food and its potential use in animal feeding.
AB  - The bioconversion of vineyard pruning and grape pomace by Pleurotus spp. using a
      solid state fermentation (SSF) was evaluated. Fruiting body production and
      chemical changes in the substrates after harvesting were measured. Biological
      efficiency and bioconversion ranged from 37.2 to 78.7% and from 16.7 to 38.8%,
      respectively. The best substrates for mycelial growth and mushroom yield were the
      mixtures with higher vineyard pruning content. Inclusion of pruning content had
      higher phenolic components and total sugars, better C/N ratio, and lower crude
      fat and total nitrogen than pomace. On the contrary, mycelium grew more slowly
      and scarcely in all treatments with 100% grape pomace. Moisture, protein, fat,
      and lignin contents were generally higher in mixtures with higher pomace
      proportion, whereas neutral detergent fiber, hemicellulose, and cellulose
      contents were higher with pruning content. Pleurotus strains may act depending on
      the availability of fiber fractions of substrate, and dynamic changes in
      digestion might occur as these fractions change during fungal growth. The
      recycling of viticulture residues through SSF by Pleurotus has great potential to
      produce human food and yields an available high-fiber feed for limited use in
      ruminants.

PMID- 11958619
TI  - Continuous whey fermentation using kefir yeast immobilized on delignified
      cellulosic material.
AB  - Delignified cellulosic-supported biocatalyst, prepared by immobilization of kefir
      yeast on delignified cellulosic material (DCM), was found to be suitable for
      continuous, modified whey fermentation. The modified whey contained 1% raisin
      extract and molasses. Ethanol productivities ranged from 3.6 to 8.3 g L(-1)day(
      1), whereas parameters such as ethanol concentration, residual sugars, and daily
      fermented whey productivity were acceptable for the production of potable alcohol
      and alcoholic drinks in industrial fermentations. The continuous fermentation
      bioreactor was operated for 39 days, stored for 18 days at 4 degrees C, and
      operated again for another 15 days without any diminution of the ethanol
      productivity. The concentrations of higher alcohols (propanol-1, isobutyl
      alcohol, and amyl alcohols) were low. The main volatile byproducts formed in the
      continuous process were similar to those observed in alcoholic beverages, and the
      fermented whey had a good aroma. The concentrations of higher alcohols were very
      low when compared to that of ethyl acetate, therefore resulting in a quality
      product. The possibility of using such a process for the production of potable
      alcohol or a novel, low-alcohol content drink is proposed.

PMID- 11958620
TI  - Biodegradation of gamma-hexachlorocyclohexane (lindane) and alpha
      hexachlorocyclohexane in water and a soil slurry by a Pandoraea species.
AB  - Isomers of 1,2,3,4,5,6-hexachlorocyclohexane (HCH) were some of the most widely
      used pesticides. Despite reduction in their production and use, HCH isomers
      present a serious environmental hazard. In this study, two bacterial isolates
      (LIN-1 and LIN-3) that can grow on gamma-HCH as a sole source of carbon and
      energy were isolated from an enrichment culture. In liquid cultures of LIN-1 and
      LIN-3, 25.0 and 45.5% removal of gamma-HCH, respectively, were achieved in 2
      weeks. LIN-3 was identified as Pandoraea sp. by 16S rRNA gene sequence analysis
      (99% identity). Pandoraea sp. substantially degraded both gamma- and alpha-HCH
      isomers at concentrations of 10-200 mg L(-1) in liquid cultures. After 8 weeks of
      incubation in liquid culture, 89.9 and 93.3% of the gamma- and alpha-HCH isomers
      declined, respectively, at an initial concentration of 150 mg L(-1). In soil
      slurry cultures of Pandoraea sp., simulating a soil slurry phase bioremediation
      treatment, substantial decreases in the levels of the HCH isomers were observed
      at concentrations of 50-200 mg L(-1). After 9 weeks, 59.6 and 53.3%
      biodegradations of gamma- and alpha-HCH isomers, respectively, were achieved at
      150 mg L(-1). Using two 23-mer oligonucloetide primers targeting the 330 bp
      region of the 16S rRNA gene of Pandoraea sp., an approximately 330 bp PCR product
      was successfully amplified from DNA templates prepared from bacterial colonies
      and soil slurry culture. This system provides a direct and rapid PCR-based
      molecular tool for tracking Pandoraea sp. strain LIN-3 in water and soils. These
      results have implied implications for the treatment of soils and water
      contaminated with HCH isomers.

PMID- 11958621
TI  - Effects of extrusion temperature and dwell time on aflatoxin levels in
      cottonseed.
AB  - Cottonseed is an economical source of protein and is commonly used in balancing
      livestock rations; however, its use is typically limited by protein, fat,
      gossypol, and aflatoxin contents. Whole cottonseed was extruded to determine if
      the temperature and dwell time (multiple stages of processing) associated with
      the process affected aflatoxin levels. The extrusion temperature study showed
      that aflatoxin levels were reduced by an additional 33% when the cottonseed was
      extruded at 160 degrees C as compared to 104 degrees C. Furthermore, the multiple
      pass extrusion study indicated that aflatoxin levels were reduced by an
      additional 55% when the cottonseed was extruded four times as compared to one
      time. To estimate the aflatoxin reductions due to extrusion temperature and dwell
      time, the least mean fits obtained for the individual studies were combined.
      Total estimated reductions of 55% (three stages of processing at 104 degrees C),
      50% (two stages of processing at 132 degrees C), and 47% (one stage of processing
      at 160 degrees C) were obtained from the combined equations. If the extreme
      conditions (four stages of processing at 160 degrees C) of the evaluation studies
      are applied to the combined temperature and processing equation, the resulting
      aflatoxin reduction would be 76%.

PMID- 11958622
TI  - Heterocyclic acetals from glycerol and acetaldehyde in Port wines: evolution with
      aging.
AB  - In Port wine, isomers of glycerol and acetaldehyde acetals have been found at
      total contents ranging from 9.4 to 175.3 mg/L. During oxidative aging, the
      concentrations of the 5-hydroxy-2-methyl-1,3-dioxane and 4-hydroxymethyl-2-methyl
      1,3-dioxolane isomers increased with time showing a linear correlation (r >
      0.95). The flavor threshold for the mixture of the four isomers was evaluated in
      wine at 100 mg/L. Thus, it is expected that they contribute to "old Port wine"
      aroma in wines older than 30 years. Experiments with model solutions and wine
      clearly demonstrated that SO(2) combines with acetaldehyde and blocks the
      acetalization reaction.

PMID- 11958623
TI  - Effects of storage conditions on furocoumarin levels in intact, chopped, or
      homogenized parsnips.
AB  - Furocoumarins represent a family of natural food constituents with phototoxic and
      photomutagenic properties. They are found mainly in plants belonging to the
      Rutaceae and Umbilliferae such as celery, carrots, and parsnips. Parsnips
      (Pastinaca sativa L.) have become more and more popular as a vegetable, e.g., as
      a constituent of or ingredient in baby food. Previous work has shown that
      microbial infection of parsnip roots can result in a dramatic increase in
      furocoumarin levels. In this study, freshly harvested parsnips were stored as
      whole roots, pieces (cubes), or homogenate at +4 degrees C or -18 degrees C over
      various time periods under standard conditions. It was found that furocoumarin
      concentrations (sum of five furocoumarins: angelicin, isopimpinellin, 5
      methoxypsoralen, 8-methoxypsoralen, and psoralen) in freshly harvested parsnips,
      analyzed by HPLC after extraction with diethyl ether and sequential solid phase
      (reversed-phase and silica) extraction, was generally lower than 2.5 mg/kg, and
      storage of parsnips in any form investigated at -18 degrees C over up to 50 days
      did not lead to a marked increase in furocoumarin levels. In contrast, storage of
      whole parsnips, but not of cubes or homogenate, at +4 degrees C resulted in a
      marked biphasic increase of furocoumarin concentrations after 7 and 38 days of
      storage up to levels of about 40 mg/kg. A dramatic increase in furocoumarin
      concentrations up to 566 mg/kg was observed when whole parsnips obtained from the
      market were kept at room temperature over 53 days, resulting in a visible
      microbial (mold) infection. Baby food products from the German market containing
      parsnips as an ingredient or constituent showed furocoumarin levels < or =0.41
      mg/kg, suggesting that properly stored roots/preparations have been used. It is
      recommended that, after harvesting, parsnips be kept at -18 degrees C or under
      other conditions that prevent microbial infections.

PMID- 11958624
TI  - Composition of the volatiles from intact and mechanically pierced tea aphid-tea
      shoot complexes and their attraction to natural enemies of the tea aphid.
AB  - The volatile components from intact tea shoots (ITS), obtained by air
      entrainment, were identified by their mass spectra and retention times and
      confirmed by comparison with standard samples. They are E-2-hexenal, ocimene, Z-3
      hexenyl acetate, Z-3-hexen-1-ol, butanoic acid-3-hexenyl ester, linalool, 1
      octanol, geraniol, and indole. Volatiles from mechanically pierced tea shoots
      (MPTS) were identified as E-2-hexenal, ocimene, Z-3-hexen-1-ol, butanoic acid-3
      hexenyl ester, linalool, geraniol, indole, E-2-hexenoic acid, Z-3-hexenyl
      formate, methyl salicylate, and benzyl alcohol, and volatiles from tea aphid-tea
      shoot complexes (TATSC) were identified as E-2-hexenal, ocimene, Z-3-hexenyl
      acetate, Z-3-hexen-1-ol, linalool, geraniol, indole, benzaldehyde, and E-2
      hexenoic acid. Z-3-Hexen-1-ol is the main component in the three different types
      of volatiles, and the amount of benzaldehyde in TATSC volatiles is very ample.
      The attraction of the volatiles from ITS, MPTS, and TATSC, and the nine
      components of TATSC volatiles to the natural enemies, the coccinellid, Coccinella
      septempunctata, the parasite, Aphidius sp., and the lacewing, Chrysopa sinica,
      were determined by electroantennogram (EAG) and the wind tunnel bioassay. TATSC
      volatiles and benzaldehyde elicited much larger EAG responses and stronger upwind
      flight and arresting behavior from each natural enemy in the wind tunnel than
      other infochemicals.

PMID- 11958625
TI  - Rotenone residues on olives and in olive oil.
AB  - The disappearance of rotenone on olives under field conditions was studied. The
      field data showed that rotenone residues on olives decreased with a half-life
      (t(1/2)) of 4.0 days. After pre-harvest time (10 days) the residues were higher
      than the maximum residue level fixed in Italy (0.04 mg/kg). Experiments with
      model systems showed that the mechanism of disappearance of rotenone is not
      related to evaporation, thermodegradation, or co-distillation, but only to
      photodegradation. When the olives were processed for oil, the residues in the oil
      were higher than the residues on the olives by a factor of 2.4-4.8.

PMID- 11958626
TI  - Influence of cultivar on quality parameters and chemical composition of
      strawberry fruits grown in Brazil.
AB  - Six strawberry cultivars grown on the same commercial plantation in Brazil were
      evaluated for their chemical composition and quality attributes at the ripe
      stage. The profiles of the main soluble sugars, ascorbic acid, and anthocyanins
      were also obtained during the developmental stages. Results showed significant
      differences among cultivars in all of the investigated parameters. Cv. Campineiro
      showed an average value for texture of 0.63 N, half the value found for cv. Oso
      Grande. Anthocyanin content ranged from 13 (cv. Campineiro) to 55 (cv. Mazi)
      mg/100 g. Total ascorbic acid found for cv. Campineiro (85 mg/100 g) was twice
      the amount found in cv. Dover (40 mg/100 g). Fructose was the predominant soluble
      sugar in almost all cultivars. The proportion among the main soluble sugars
      (fructose, sucrose, and glucose) was similar for Oso Grande and Toyonoka
      cultivars. The flavonol content (quercetin plus kaempferol derivatives) ranged
      from 2.7 to 7.1 mg/100 g, with a mean value of 6.1 mg/100 g, whereas free ellagic
      acid ranged from 0.9 to 1.9 and total phenolics varied from 159 to 289 (mean 221)
      mg/100 g.

PMID- 11958627
TI  - Quantification of the group B soyasaponins by high-performance liquid
      chromatography.
AB  - High-performance liquid chromatographic methods were developed for the isolation
      and quantitative determination of the group B soyasaponins, including 2,3-dihydro
      2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP)-conjugated soyasaponins alphag,
      betag, and betaa, and their non-DDMP counterparts, soyasaponins V, I, and II,
      respectively, with formononetin used as the internal standard. The limits of
      quantification for soy products were 0.11-4.86 micromol/g. The within-day and
      between-days assay coefficients of variation were <9.8 and < 14.3%, respectively.
      The group B soyasaponin concentrations in 46 soybean varieties ranged from 2.50
      to 5.85 micromol/g. Soy ingredients (soybean flour, toasted soy hypocotyls, soy
      protein isolates, textured vegetable protein, soy protein concentrates, and
      Novasoy) and soy foods (commercial soy milk, tofu, and tempeh) contained the
      group B soyasaponins from 0.20 to 114.02 micromol/g. There was no apparent
      correlation between isoflavone and soyasaponin concentrations in the soy products
      examined.

PMID- 11958628
TI  - Chemical composition and enzymatic degradability of xylem and nonxylem walls
      isolated from alfalfa internodes.
AB  - During plant maturation, degradability of alfalfa (Medicago sativa L.) stems
      declines due to accumulation of highly lignified xylary tissue. Xylem and
      nonxylem tissues dissected from lower alfalfa internodes were analyzed for cell
      wall constituents and degradability. Cell walls comprised 740 mg g(-1) of xylem
      and 533 mg g(-1) of nonxylem tissues. Xylem tissues contributed about 60% of the
      cell wall mass in internodes. Xylem walls contained 28% lignin, 4% pectin, 29%
      hemicellulose, and 39% cellulose as compared to 15% lignin, 25% pectin, 30%
      hemicellulose, and 30% cellulose in nonxylem walls. Fungal enzymes hydrolyzed 22
      and 73% of the structural carbohydrates in xylem and nonxylem walls,
      respectively. In both cell wall fractions, the release of xylose was 56-90% lower
      than that of other sugars, indicating that lignin preferentially restricted xylan
      degradation in secondary walls and xyloglucan degradation in primary walls.
      Elucidation of lignin-xylose interactions may reveal strategies for improving
      fiber degradability of alfalfa.

PMID- 11958629
TI  - Chemical marker for ALS-inhibitor herbicides: 2-aminobutyric acid proportional in
      sub-lethal applications.
AB  - A chemical profiling technique for sub-lethal acetolactate synthase (ALS)
      inhibitor herbicides (e.g., sulfonylureas, imidazolines, triazolopyrimidine
      sulfonanilides, and pyrimidyloxy salicylic) was developed using 2-aminobutyric
      acid, and was found to be directly proportional to application rates in field
      studies on two varieties of potato plants. An uncomplicated, benign-by-design
      analytical method for the determination of 2-aminobutyric acid in plant tissue
      was developed. The method is simple, fast, and automated, entailing a water
      trichloroacetic acid extraction followed by precolumn on-line derivatization
      using o-phthalaldehyde (OPA) solution and liquid chromatographic analyses. Use of
      reagents and chlorinated organic solvents, and generation of waste, are minimized
      as compared to other ALS-inhibitor herbicide analytical techniques. Recoveries
      for a series of fortified plant tissues ranged from 82 to 103%. Two 20-day field
      trials on two potato varieties, Russet Burbank and Shepody, were conducted during
      the 2000 and 2001 growing seasons. The study demonstrated that the 2-aminobutyric
      acid method is an excellent, selective chemical marker technique for ALS
      inhibitor herbicides for real world plant matrixes.

PMID- 11958630
TI  - Effect of soil moisture and sample depth on pesticide photolysis.
AB  - The effects of soil depth and moisture on pesticide photolysis were studied.
      Moist soil at depths of 3, 2.5, 2, 1.5, 1, and 0.5 mm were each dosed at 2.5
      microg/g with (14)C-niclosamide and photolyzed under a xenon lamp at constant
      temperature. Samples were removed after 20, 40, 110, and 153 h of continuous
      irradiation. The decrease in percent of niclosamide and the appearance of
      degradates were followed by analyzing the soil extracts by HPLC. A corresponding
      set of experiments used air-dried soil. An experiment was also performed using
      initially moist soil which was permitted to dry during photolysis but returned to
      moist conditions at each sampling. Qualitative and quantitative differences were
      found in the rate and route of degradation of niclosamide under these conditions.
      These differences have resulted from a combination of reduced photochemical
      activity and microbial population in dry soil. The half-lives of niclosamide in
      the dry soils were 2 to 5 times longer than those in the moisture-maintained
      soil. There was also a noticeable difference in the half-lives in soil of
      different depths. Moisture-maintained soil showed a uniform linear increase in
      half-life from 95 to 195 h as soil depth increased from 0.5 mm to 3.0 mm. With
      air-dried soil the half-lives were greatly dependent on soil depth, showing a
      much broader range of 199 h at 0.5-mm to 1064 h in 3.0-mm soil. An experimental
      design is described which maintains soil temperature and moisture to preset
      conditions.

PMID- 11958631
TI  - Volatile metabolites from actinomycetes.
AB  - Twenty-six Streptomyces spp. were screened for their volatile production capacity
      on yeast starch agar. The volatile organic compounds (VOCs) were concentrated on
      a porous polymer throughout an 8-day growth period. VOCs were analyzed by gas
      chromatography with flame ionization detection and identified or characterized by
      gas chromatography-mass spectrometry. A total of 120 VOCs were characterized by
      retention index and mass spectra. Fifty-three compounds were characterized as
      terpenoid compounds, among which 18 could be identified. Among the VOCs were
      alkanes, alkenes, alcohols, esters, ketones, sulfur compounds, and isoprenoid
      compounds. Among the most frequently produced compounds were isoprene, acetone, 1
      butanol, 2-methyl-1-propanol, 3-methyl-3-buten-1-ol, 3-methyl-1-butanol, 2-methyl
      1-butanol, cyclopentanone, dimethyl disulfide, dimethyl trisulfide, 2
      phenylethanol, and geosmin. The relationship between the excretion of geosmin and
      the production of spores was examined for one isolate. A good correlation between
      headspace geosmin and the number of spores was observed, suggesting that VOCs
      could be used to indicate the activity of these microorganisms in heterogeneous
      substrates.

PMID- 11958632
TI  - Influence of oak wood on the aromatic composition and quality of wines with
      different tannin contents.
AB  - The aromatic compounds associated with aging in wood have been studied in
      Monastrell wines containing different quantities of tannin. Analyses were carried
      out before and after a six month period in wooden barrels (225 L) of American and
      French (Allier) medium-toasted oak. Three classes of wine were made: one from a
      free-run must; one to which enological tannin was added; and one to which was
      added the wine obtained by pressing the grape pomaces. The aromas were determined
      by GC-MS, and the quality was evaluated by a group of expert tasters. The
      aromatic compounds, some of which came from the wines themselves and others which
      came from the wood, all increased in concentration by the end of the aging
      process. The ratio between cis- and trans-whiskylactone contents in wines
      reflected the different types of oak wood used. The note "vanilla" used by the
      tasters is probably not totally due to the presence of vanillin. The wines of
      best quality were those with a natural tannin content which had been aged in
      American oak, whereas the wines to which enological tannin had been added but
      aged in the same wood were considered the worst. An equalizing effect on the
      sensorial wines qualities was seen to result from the use of French oak. The
      furfural, eugenol, and cis-, and in some cases trans-, whiskylactone contents
      identified the wines from the different classes of wood. The wood from which the
      barrels were made had a greater effect on wines differentiation than the tannin
      content.

PMID- 11958634
TI  - Analysis of volatiles from Spanish honeys by solid-phase microextraction and gas
      chromatography-mass spectrometry.
AB  - Headspace solid-phase microextraction (SPME), followed by gas chromatography (GC)
      mass spectrometry (MS) determination, has been used for the analysis of honey
      volatiles. Two SPME fibers were employed to study the composition of volatiles
      from various types of Spanish honeys. The best results were obtained with the
      Carboxen/PDMS fiber, using a homogenization time of 1 h at 70 degrees C and a
      sampling period of 30 min. A total of 35 compounds were detected, most of them
      identified by GC-MS and quantified using external standards. Differences in the
      composition of honey volatiles were obtained, and these results allowed the
      differentiation of honeys. However, further studies are necessary to confirm the
      utility of this technique as an alternative tool for the characterization of the
      floral origin of honeys.

PMID- 11958633
TI  - Investigations of aroma volatile biosynthesis under anoxic conditions and in
      different tissues of "Redchief Delicious" apple fruit (Malus domestica Borkh.).
AB  - Disks from different tissues were obtained from "Redchief Delicious" apple fruit
      (Malus domestica Borkh.) and analyzed for the ability to metabolize 1-pentanol as
      well as synthesize constitutive esters and alcohols under anoxic and aerobic
      conditions. The skin tissue displayed a greater capacity to synthesize pentanal,
      pentyl acetate, pentyl propionate, pentyl butyrate, and pentyl hexanoate than the
      hypanthial and carpellary tissues during incubation with 1-pentanol. With the
      exception of pentyl acetate and pentyl propionate biosynthesis, the hypanthial
      tissue synthesized these compounds at a higher rate than the carpellary tissue.
      Anoxia inhibited both constituent and 1-pentanol-derived ester biosynthesis.
      While anoxia inhibited ester biosynthesis, ethanol biosynthesis increased at a
      greater rate in tissue disks held under these conditions. Biosynthesis of 1
      butanol, 2-methyl-1-butanol, and 1-hexanol was greater in tissue disks held in
      air during the first part of the measurement period and dropped off more rapidly
      than those transpiring in tissue disks held under anoxic conditions. The
      biosynthetic rates of all esters, both constituent and 1-pentanol-derived,
      increased as a result of air exposure. While hypoxic or anoxic conditions may
      promote ethanol synthesis, these conditions also appear to inhibit the formation
      of the ethanol-derived esters partially responsible for the off-flavor in apples
      attributed to ultralow O(2) controlled atmosphere storage.

PMID- 11958635
TI  - Supercritical fluid extraction of lycopene from tomato processing byproducts.
AB  - Tomato seeds and skins acquired from the byproduct of a local tomato processing
      facility were studied for supercritical fluid extraction (SFE) of phytochemicals.
      The extracts were analyzed for lycopene, beta-carotene, alpha-carotene, alpha
      tocopherol, gamma-tocopherol, and delta-tocopherol content using high-performance
      liquid chromatography-electrochemical detection and compared to a chemically
      extracted control. SFEs were carried out using CO(2) at seven temperatures (32-86
      degrees C) and six pressures (13.78-48.26 MPa). The effect of CO(2) flow rate and
      volume also was investigated. The results indicated that the percentage of
      lycopene extracted increased with elevated temperature and pressure until a
      maximum recovery of 38.8% was reached at 86 degrees C and 34.47 MPa, after which
      the amount of lycopene extracted decreased. Conditions for the optimum extraction
      of lycopene from 3 g of raw material were determined to be 86 degrees C, 34.47
      MPa, and 500 mL of CO(2) at a flow rate of 2.5 mL/min. These conditions resulted
      in the extraction of 61.0% of the lycopene (7.19 microg lycopene/g).

PMID- 11958636
TI  - In vitro stability and chemical reactivity of thiosulfinates.
AB  - A model reaction system was used to generate pure thiosulfinates (3) from S
      alk(en)yl-L-cysteine sulfoxides (1) to facilitate studies on the intrinsic pH and
      thermal sensitivities of individual thiosulfinate species. Thiosulfinate decay
      could be characterized as first-order processes over the pH range of 1.2-9.0 and
      at 20-80 degrees C. The stability of thiosulfinates was greatest at pH 4.5-5.5,
      followed by pH 1.2, pH 6.5-7.5, and pH 8.0-9.0. Thiosulfinates with longer and
      saturated alk(en)yl groups were generally more stable than those with shorter and
      unsaturated alk(en)yl groups. Thiosulfinates underwent thioalkyl-exchange
      reactions at pH 8-9 without loss of total thiosulfinate levels within 60-90 min
      at 20 degrees C.

PMID- 11958637
TI  - Fate and kinetic modeling of reactivity of alkanesulfenic acids and
      thiosulfinates in model systems and onion homogenates.
AB  - The dynamic changes in thiosulfinate profiles were studied in reaction systems
      containing a crude onion alliinase, S-alk(en)yl-L-cysteine sulfoxide substrates
      (1) and preformed thiosulfinates (4). Regioisomeric excesses of one of two
      possible heterologous 4 species (RS(O)SR', where R does not equal R') could be
      manipulated under conditions where alliinase, 1, and 4 levels were varied.
      Regioisomeric excesses could be explained by a thiosulfinate (4)/alkanesulfenic
      acid (2) trapping mechanism, with the greatest control over product profile
      governed by the rate of 2 generation in the system. The series of reactions
      existing in this dynamic reaction system was kinetically modeled with reasonable
      fits to the experimental data. The application of the 4/2 trapping strategy to
      manipulate thiosulfinate and related organosulfur product profiles in diluted
      onion homogenates was demonstrated using exogenous MeS(O)SMe (4a), PrS(O)SPr
      (4c), and AllS(O)SAll (4d) as the preformed thiosulfinate.

PMID- 11958638
TI  - Physicochemical and structural properties of oat globulin polymers formed by a
      microbial transglutaminase.
AB  - Oat globulin was polymerized by a microbial transglutaminase (TG), and some
      physicochemical and functional properties of polymers were studied. Reversed
      phase HPLC revealed that the number of epsilon-(gamma-glutamyl) lysine isopeptide
      bonds formed after 4 h of enzyme incubation was 2.21 micromol/g of protein. SDS
      PAGE showed that the oat globulin acidic polypeptides (AP) were more susceptible
      to polymerization than the basic polypeptides (BP), and the reactivities of both
      AP and BP were enhanced by the addition of other substrate proteins. Differential
      scanning calorimetry showed that both the denaturation temperature and
      denaturation enthalpy were decreased after TG treatment. Fourier transform
      infrared spectroscopy revealed marked increases in the intensity of two
      intermolecular beta-sheet bands associated with aggregate formation but little
      conformational changes in the polymerized protein. TG incubation led to
      progressive changes in flow properties of oat globulin dispersions, indicating
      enhanced pseudoplasticity and increased viscosity and yield stress.

PMID- 11958639
TI  - Functional properties of oat globulin modified by a calcium-independent microbial
      transglutaminase.
AB  - Oat globulin was modified by a calcium-independent microbial transglutaminase
      (TG). The TG-polymerized protein had higher solubility than the control at acidic
      pH and had improved water- and fat-binding properties. Incubation of 10% (w/v)
      oat globulin dispersions in the presence of TG at 37 degrees C led to the
      formation of a well-developed viscoelastic gel network with a microstructure
      characterized by thick strands and large clusters. The TG-induced gels had higher
      modulus values, lower loss tangent values, and lower frequency dependency than
      the heat-induced gels. The TG-induced gel system has the characteristics of
      classical polymer gel with permanent "chemical" cross-links, whereas the heat
      denatured system has the characteristics of a temporary "physical" gel with
      breakable cross-links. Fourier transform infrared spectroscopy showed marked
      shift and intensity changes in several major bands, suggesting pronounced changes
      in protein conformation during TG-induced gelation. Aggregation of protein
      molecules was also indicated by the progressive increases in two infrared bands
      (1679-1682 and 1622-1625 cm(-)(1)) associated with the formation of
      intermolecular beta-sheets and strands. Results suggest that new food polymers
      with unique functionality can be produced from oat globulin treated with TG and
      that elastic gels can be formed near neutral pH, instead of the alkaline pH
      required for thermally induced oat globulin gels.

PMID- 11958640
TI  - Temperature and pH dependence of the autoxidation rate of bovine, ovine, porcine,
      and cervine oxymyoglobin isolated from three different muscles--Longissimus
      dorsi, Gluteus medius, and Biceps femoris.
AB  - This study examined the temperature and pH dependence of the in vitro
      autoxidation rate of bovine, ovine, porcine, and cervine oxymyoglobin that had
      been isolated and purified from three muscles of different oxidative stability-
      Longissimus dorsi, Gluteus medius, and Biceps femoris. To avoid obtaining
      unreliable estimates of autoxidation rate as has occurred in many previous
      studies, in this study, precautions were taken to eliminate the effects of
      freezing, chemical reduction with hydrosulfite, and contaminating metal ions on
      the reaction rate. When these precautions were taken, the rate constants for the
      different myoglobins studied were similar to each other but were 2-7-fold lower,
      and the Ea (activation energy) was 20-100% higher than that reported in most
      previous studies. The type of muscle the myoglobin was isolated from had no
      effect on the reaction rate or the Ea; however, the species did have a
      significant effect (p < 0.05) with porcine myoglobin having a 10% lower reaction
      rate and a 20% lower Ea than myoglobin from the other species. Increasing the
      reaction pH from 5.50 to 6.50 produced an exponential increase in reaction rate
      but only a small curvilinear change in Ea that had a maximum at pH 6.00.

PMID- 11958641
TI  - Comparative studies on antigenicity and allergenicity of native and denatured egg
      white proteins.
AB  - The binding activities of IgG and IgE antibodies from egg-allergic patients to
      physically or chemically treated egg white proteins were examined and compared
      with those of rabbit anti-egg white IgG antibodies. The sera from eight patients
      and four rabbit antibodies were used in this study. The binding activities of
      human IgG antibody to partially denatured ovotransferrin (Tf), ovalbumin (OA),
      and lysozyme (Lys) forms were increased, whereas carboxymethylation (RCM) and
      heat treatment caused a dramatic decrease in the antigenicity of Tf and ovomucoid
      (OVM). Tf and OVM were major immunogenic antigens for the rabbit IgG response.
      Urea also caused Tf to exhibit greater rabbit IgG binding activity. In contrast,
      human and rabbit antibodies did not react with ovomucin. Partially denatured Tf
      and Lys also induced strong IgE binding activities. The allergenicity of Tf, OVM,
      and Lys was decreased by RCM, whereas OA retained its binding capacity. These
      results suggested that anti-OA IgE recognizes more sequential epitopes and that
      anti-OVM and Lys antibodies recognize both conformational and sequential
      epitopes. Tf and OVM were dominant allergens for the IgE antibodies of
      anaphylaxis patients, whereas IgE from atopic patients bound more strongly with
      OA and OVM.

PMID- 11958642
TI  - Biologically active lipids with antiatherogenic properties from white wine and
      must.
AB  - Wine can be considered an integral part of the Mediterranean diet. Evidence from
      epidemiological and experimental studies suggests a protective effect against the
      development of coronary heart disease with moderate consumption of wine and
      especially red wine. The exact nature of the protective effect remains to be
      established. However, mechanisms including low-density lipoproteins oxidation,
      inhibition of platelet aggregation, modification of eicosanoid metabolism, and
      endothelium-dependent relaxation of blood vessels are recognized as contributory.
      In this study, a new approach has been examined, based on previous reports that
      platelet-activating factor (PAF) is involved in atherogenesis. An attempt was
      made to detect key components in wine/must that through inhibition of PAF action
      may contribute to the protective role of white wine/must against atherosclerosis.
      More specifically, polar lipids from four wines and three musts were fractionated
      by thin-layer chromatography, and fractions were tested in vitro for their
      ability to inhibit PAF and thrombin-induced washed rabbit platelet aggregation
      and/or to cause platelet aggregation. On the basis of the above results, a white
      wine from the principal Greek grape Rompola and its respective must with and
      without extra yeast were chosen for further high-performance liquid
      chromatography separation. A significant number of biological active lipids were
      detected, and structural data for the most active lipids are provided.

PMID- 11958643
TI  - Structures and physicochemical properties of six wild rice starches.
AB  - Starches from six wild rice cultivars were studied for their chemical structures
      and physicochemical properties and compared with a long-grain rice starch. The
      six wild rice starches were similar in morphological appearance, X-ray
      diffraction patterns, swelling power, and water solubility index but different in
      amylose content, beta-amylolysis limit, branch chain length distribution, thermal
      properties, and pasting properties. The structure of the wild rice amylopectins
      was close to that of waxy rice amylopectin with more branching and a larger
      proportion of short branch chains of degree of polymerization 6-12 as compared
      with that of amylopectin from rice starch with a similar amylose content. The
      differences in branch chain length distribution of amylopectin and amylose
      content were assumed to contribute to the differences in physicochemical
      properties among the six wild rice starches as well as to the differences between
      the wild rice starches and the rice starch.

PMID- 11958644
TI  - Characterization of isoflavones and their conjugates in female rat urine using
      LC/MS/MS.
AB  - Isoflavone phytoestrogens found in soybeans are the most widely studied
      phytochemicals in human diets and soy infant formulas. The health benefits of the
      isoflavones daidzein and genistein have been reported, and concerns about
      potential adverse effects have also been raised. However, the results of direct
      analysis of isoflavones and their metabolites in biological fluids after
      consumption of soy-containing diets are scarce. This study describes an LC/MS/MS
      method for the analysis of isoflavones and their metabolites in the urine of
      female rats fed diets made with soy protein isolate. Five isoflavones (daidzein,
      genistein, glycitein, dihydrodaidzein, and O-desmethylangolensin) were identified
      by comparison with authentic standards. Seventeen conjugates of isoflavones were
      characterized in the urine, the most unusual being genistein 5-glucuronide and
      four glucuronide conjugates of reductive metabolites of daidzein. The application
      of LC/MS/MS to analyze isoflavone metabolites is simple and sensitive, and
      appears to be an excellent method for determining the bioavailability and
      metabolism of food phytochemistry.

PMID- 11958645
TI  - Human apo A-I and rat transferrin are the principal plasma proteins that bind
      wine catechins.
AB  - The processes of absorption, blood transport, tissular distribution, metabolism,
      and excretion are at present understood very little. The aim of this study was to
      investigate blood transport and identify which principal plasma proteins in
      humans and rats bind to monomeric catechin and procyanidins in red wine ex vivo.
      Human and rat plasma and serum were incubated with (+)-catechin and procyanidins
      from grape seed, the origin of red wine catechins. Proteins were separated by SDS
      PAGE and native-PAGE to determine which proteins bound to these compounds. The
      principal protein that bound to (+)-catechin in each species was sequenced. SDS
      PAGE showed that (+)-catechin and procyanidins mainly bound to a protein of about
      80 kDa in rats and 35 kDa in humans. Their sequencing indicated that these
      proteins were apo A-I in humans and transferrin in rats. The fact that red wine
      procyanidins bind to both proteins suggests that they may have a role in reverse
      cholesterol transport and in the oxidizing action of iron.

PMID- 11958646
TI  - Butyltin compounds in Portuguese wines.
AB  - Butyltin compounds are widespread contaminants that have also been found in some
      wines. The purpose of the present work was to make a survey of butyltin compounds
      in Portuguese wines. Forty-three table wines and 14 Port wines were analyzed for
      butyltin contents by using solid-phase microextraction gas chromatography mass
      spectrometry (SPME-GC-MS). In 14% of the analyzed wine samples, measurable
      dibutyltin (DBT) was found at concentrations ranging between 0.05 and 0.15
      microg/L as Sn. Monobutyltin (MBT) was also observed (0.05 microg/L as Sn) in
      just a single wine. A search for the possible sources of DBT residues found in
      the wines was carried out. Therefore, some plastics and oak wood used in the
      process of wine-making, which have been directly in contact with the musts or the
      wines, were studied to check their possible release of butyltins. The eventual
      presence of DBT was also tested directly along the vinification process, from the
      must to the finished product. The results suggest that high-density polyethylene
      containers used in the transfer of wine in an early stage of the vinification
      process may be the main sources of these contaminants. Therefore, it is
      recommendable that plastic materials to be used in wineries be previously tested
      for the release of butyltin compounds.

PMID- 11958647
TI  - Verification of dynamic and segmental IMRT delivery by dynamic log file analysis.
AB  - A program has been developed to evaluate the delivered fluence of step-and-shoot
      segmental and sliding window dynamic multileaf collimator (MLC) fields. To
      automate these checks, a number of tools have been developed using data available
      from the dynamic log files that can be created each time a dynamic delivery
      occurs. Experiments were performed with a Varian 2100EX with a 120 leaf MLC
      equipped with dynamic capabilities. A dynamic leaf sequence is delivered and
      measured with film or an amorphous silicon imager. After delivery, the dynamic
      log file is written by the accelerator control system. The file reports the
      expected and actual position for each leaf and the dose fraction every 0.055
      seconds. Leaf trajectories are calculated from this data and expected and actual
      fluence images are created from the difference of opposing leaf trajectories.
      These images can be compared with the expected delivery, measurements, and
      calculations of fluence. Tools have been developed to investigate other aspects
      of the delivery, such as specific leaf errors, beam hold-off flags sent by the
      control system to the MLC, and gap widths. This program is part of a semi
      automated quality assurance (QA) system for pretreatment fluence verification and
      daily treatment verification of dynamic multileaf collimation (DMLC) delivery.

PMID- 11958648
TI  - Verification of dose calculations with a clinical treatment planning system based
      on a point kernel dose engine.
AB  - Dose calculations with a collapsed cone algorithm implemented in a clinical
      treatment planning system have been studied. The algorithm has been evaluated in
      homogeneous as well as in heterogeneous media, and the results have been compared
      to measurements and Monte Carlo simulations. Commonly encountered clinical beam
      configurations as well as more complex geometries have been pursued to test the
      limitations of the model. The results show that the accuracy level reached allows
      for clinical use. Some situations, e.g., large wedge beams and dose calculations
      in the build up region, not specific to the collapsed cone model, show deviations
      (outside +/- 3%) compared to measurements.

PMID- 11958649
TI  - Verification of prostate treatment setup using computed radiography for portal
      imaging.
AB  - A non-film-based system was used to obtain high quality portal film images.
      Digital portal images were obtained with a computed radiography (CR) system, in
      which the film is replaced with a photostimulable phosphor plate. Digital
      processing of portal images enhanced the display contrast using regional
      histogram equalization. The images were compared to images on radiographic film,
      exposed in the same cassette. The contrast-enhanced CR images of prostate
      treatment fields facilitated identification of the entire contour of the ischium,
      the location of the pubic symphysis, and the ischial tuberosity to determine the
      anterior and inferior locations of the prostate and bladder. Identifying the
      coccyx on the processed portal images permits the physician to locate accurately
      the posterior wall of the rectum. In each case the quality of the CR image was
      judged by the clinician to be superior to conventional portal film. The
      identification of these anatomical structures on the portal images is clinically
      important for verifying 3D conformal therapy of the prostate. With the same CR
      system one may acquire digital treatment portal and simulation images. This
      provides a foundation for a picture archival communication system for radiation
      oncology. Existing software can be used to register these digital portal and
      simulation images to facilitate verification of treatment setup.

PMID- 11958650
TI  - Dosimetric verification of inverse planned step and shoot multileaf collimator
      fields from a commercial treatment planning system.
AB  - An inverse treatment planning (ITP) module on a commercial treatment planning
      system (TPS) (Helax AB, Uppsala, Sweden) is being used for an in-house clinical
      trial for treatment of nasopharyngeal cancer with contralateral parotid sparing.
      Intensity modulated radiation therapy (IMRT) fields are delivered by step and
      shoot multileaf collimator (MLC) with a DMLC enabled Varian 2300 CD (Varian
      Associates, Palo Alto, CA). A series of testing procedures have been devised to
      quantify the modeling and delivery accuracy of routine clinical inverse planned
      IMRT using Helax TMS and the Varian step and shoot MLC delivery option. Testing
      was done on specific aspects of the TPS modeling germane to DMLC. Measured
      relative dose factors (head scatter plus phantom scatter) for small MLC fields,
      normalized to a 10x10 cm2 non-MLC field, were found to differ by 2-3% from the
      TPS values for the smallest of the fields tested. Relative distributions for
      small off axis fields were found to be in good agreement. A process for the
      routine clinical verification of IMRT fields has been implemented. Each IMRT
      field in an inverse plan is imported into a flat water tank plan and a "beam's
      eye view" (BEV) dose distribution is generated. This is compared to the
      corresponding measured BEV dose distribution. The IMRT verification process has
      also been performed using an anthropomorphic phantom. Large clinical fields
      (i.e., greater than 14.5 cm in the leaf direction) caused difficulties due to a
      vendor specific machine restriction, and several techniques for dealing with
      these were examined. These techniques were (i) the use of static stepping of
      closed junctions, (ii) the use of two separate IMRT fields for a given gantry
      angle, and (iii) restricting the overall maximum field size used. The overall
      process has allowed implementation of an in-house protocol for IMRT use on an
      initial clinical site. Results of the verification measurements for the first ten
      patients treated at this center reveal an average maximum dose per IMRT field
      delivered of 71.0 cGy, with a mean local deviation from the planned dose of -1.2
      cGy, and a standard deviation of 2.4 cGy.

PMID- 11958652
TI  - Dosimetric parameters of three new solid core I-125 brachytherapy sources.
AB  - Monte Carlo calculations and TLD measurements have been performed for the purpose
      of characterizing dosimetric properties of new commercially available
      brachytherapy sources. All sources tested consisted of a solid core, upon which a
      thin layer of 125I has been adsorbed, encased within a titanium housing. The
      PharmaSeed BT-125 source manufactured by Syncor is available in silver or
      palladium core configurations while the ADVANTAGE source from IsoAid has silver
      only. Dosimetric properties, including the dose rate constant, radial dose
      function, and anisotropy characteristics were determined according to the TG-43
      protocol. Additionally, the geometry function was calculated exactly using Monte
      Carlo and compared with both the point and line source approximations. The 1999
      NIST standard was followed in determining air kerma strength. Dose rate constants
      were calculated to be 0.955+/-0.005, 0.967+/-0.005, and 0.962+/-0.005 cGy h(-1) x
      U(-1) for the PharmaSeed BT-125-1, BT-125-2, and ADVANTAGE sources, respectively.
      TLD measurements were in excellent agreement with Monte Carlo calculations.
      Radial dose function, g(r), calculated to a distance of 10 cm, and anisotropy
      function, F(r,theta), calculated for radii from 0.5 to 7.0 cm, were similar among
      all source configurations. Anisotropy constants, phi(an), were calculated to be
      0.941, 0.944, and 0.960 for the three sources, respectively. All dosimetric
      parameters were found to be in close agreement with previously published data for
      similar source configurations. The MCNP Monte Carlo code appears to be ideally
      suited to low energy dosimetry applications.

PMID- 11958651
TI  - CT gel dosimetry technique: comparison of a planned and measured 3D stereotactic
      dose volume.
AB  - This study presents a 3D dose mapping of complex dose distributions using an x
      ray computed tomography (CT) polymer gel dosimetry technique. Two polyacrylamide
      gels (PAGs) of identical composition were irradiated with the same four arc
      stereotactic treatment to maximum doses of 15 Gy (PAG1) and 8 Gy (PAG2). The PAGs
      were CT imaged using a previously defined protocol that involves image averaging
      and background subtraction to improve image quality. For comparison with the
      planned isodose distribution, the PAG images were converted to relative dose maps
      using a CT number-dose calibration curve or simple division. The PAG images were
      then co-registered with the planning CT images in the BrainLab treatment planning
      software which automatically provides reconstructed sagittal and coronal images
      for 3D evaluation of measured and planned dose. The hypo-intense high dose region
      in both sets of gel images agreed with the planned 80% isodose contour and was
      shifted by up to 1.5 and 3.0 mm in the axial and reconstructed planes,
      respectively. This demonstrates the ability of the CT gel technique to accurately
      localize the high dose region produced by the stereotactic treatment. The
      resulting agreement of the measured relative dose volume for PAG1 was within 3.0
      mm for the 50% and 80% isodose surfaces. However, the dose contrast was too low
      in PAG2 to allow for accurate definition of measured relative dose surfaces.
      Thus, a PAG should be irradiated to higher doses if quantitative relative dose
      information is required. Unfortunately, this implies use of an additional PAG and
      its CT number dose response since doses greater than 8-10 Gy fall outside the
      linear regions of the response.

PMID- 11958653
TI  - Quasi-independent monitor unit calculation for intensity modulated sequential
      tomotherapy.
AB  - The number of linac monitor units (MU) from intensity modulated sequential
      tomotherapy (IMST) is substantially larger than the MU delivered in conventional
      radiation therapy, and the relation between MU and dose is obscure due to
      complicated variation of the beam intensities. The purpose of this work was to
      develop a practical method of verifying the MU and dose from IMST so that the MU
      of each arced beam could be double-checked for accuracy. MU calculations for 41
      arced beams from 14 IMST patients were performed using the variables of vane open
      fraction time, field size, target depth, output factor, TMR, and derived
      intensity distribution. Discrepancy between planned and checked MU was quantified
      as 100 (MU(cal)-MU(plan))/MU(plan) percent. All 41 discrepancies were clustered
      between -5% to +4%, illustrated in a Gaussian-shaped histogram centered at -1.0+/
      3.5% standard deviation indicating the present MU calculations are in agreement
      with the planned expectations. To confirm the correctness of the present
      calculated MUs of the IMST plans, eight of the calculated IMST plans are
      performed dose verifications using their hybrid plans, which are created by
      transporting patient's IMST plan beams onto a spherical polystyrene Phantom for
      dose distribution within the Phantom. The dose was measured with a 0.07 cc
      ionization chamber inserted in the spherical Phantom during the hybrid plan
      irradiation. Average discrepancy between planned and measured doses was found to
      be 0.6+/-3.4% with single standard deviation uncertainty. The spread of the
      discrepancies of present calculated MUs relative to their planned ones are
      attributed to uncertainties of effective field size, effective planned dose
      corresponding to each arc, and inaccuracy of quantification of scattered dose
      from adjacent arced beams. Overall, the present calculation of MUs is consistent
      with what derived from treatment plans. Since the MUs are verified by actual dose
      measurements, therefore the present MU calculation technique is considered
      adequate for double-checking planned IMST MUs.

PMID- 11958654
TI  - A new geometric and mechanical verification device for medical LINACs.
AB  - The goal of quality assurance (QA) for a radiation oncology medical LINAC is to
      maintain an acceptable level of equipment performance and reliability. The
      increasing complexity of Radiation Oncology equipment and treatment techniques
      have led to increased demands on the work load of the medical physicist. Regular
      testing needs to be as efficient as possible. Generally, the QA tests, as
      recommended by the AAPM Task Group 40 for medical LINACs, can be grouped into two
      categories: dosimetry and mechanical checks. A new QA device has been developed
      that facilitates many of the daily and monthly mechanical QA checks. Its
      efficiency and speed is achieved through a set of QA tools that are mounted on a
      single platform, which is designed to fit into the accessory mount of the medical
      LINAC. Named Mini-GARD (MG), it verifies the accuracy of the digital readouts for
      gantry angles, collimator angles, and field sizes. It also tests crosshair
      position, the optical distance indicator (ODI), and patient setup laser
      alignment. It uses two calibrated digital levels for the gantry and collimator
      angle verification, an electronic tape measure for ODI verification, and a
      calibrated transparent projection scale for the remaining tests. This paper
      evaluates the stability and accuracy of the device in clinical tests over a
      period of a year. Results show that the MG is reliable and capable of measuring
      gantry and collimator angle constancy to +/-0.3 degrees, ODI constancy to +/-0.05
      cm, and field size accuracies to +/-0.05 cm.

PMID- 11958655
TI  - A quality control program for MR-guided focused ultrasound ablation therapy.
AB  - In this study, we propose a quality control program for MR-guided focused
      ultrasound (FUS) ablation treatment to assess FUS beam positioning accuracy, FUS
      power delivery accuracy, MR imaging quality, and FUS ablation system safety. A
      total of 353 sonication points in Lucite cards were measured, the average
      placement errors were -0.06 mm in the SI direction and -0.04 mm in the LR
      direction. Temperature elevation was calculated from MR phase difference images
      and the measured water proton chemical shift (WPCS) temperature coefficient. WPCS
      temperature calibration for phantoms yielded a temperature coefficient of 0.011
      ppm/degree C. Sixteen experiments were conducted using six different phantoms to
      test the reliability of FUS power delivery. SNR and RF power calculated from
      phantom images were analyzed and stored at the MR console. A computer program was
      developed to integrate the system power delivery and the MR image quality control
      into one automated process. In the clinical trial at our institution, we expect
      this quality control program to be carried out before each patient treatment. If
      measured quality control values exceeds or below the preset values, a system
      service and retest should be conducted before the treatment.

PMID- 11958656
TI  - Quality indicators of fresh frozen plasma and platelet utilization.
AB  - OBJECTIVE: To determine the normative rates of expiration and wastage for units
      of fresh frozen plasma (FFP) and platelets (PLTs) in hospital communities
      throughout the United States, and to examine hospital blood bank practices
      associated with more desirable (lower) rates. DESIGN: In 3 separate studies,
      participants in the College of American Pathologists Q-Probes laboratory quality
      improvement program collected data retrospectively on the numbers of units of FFP
      and PLTs that expired (outdated) prior to being used and that were wasted due to
      mishandling. Participants also completed questionnaires describing their
      hospitals' and blood banks' laboratory and transfusion practices. SETTING AND
      PARTICIPANTS: One thousand six hundred thirty-nine public and private
      institutions, more than 80% of which were known to be located in the United
      States. MAIN OUTCOME MEASURES: Quality indicators of FFP and PLT utilization: the
      rates of expiration and wastage of units of FFP and PLTs. RESULTS: Participants
      submitted data on 8 981 796 units of FFP and PLTs. In all 3 studies, aggregate
      combined FFP and PLT expiration rates ranged from 5.8% to 6.4% and aggregate
      combined FFP and PLT wastage rates ranged from 2.0% to 2.5%. Among the top
      performing 10% of participants (90th percentile and above), FFP and PLT
      expiration rates were 0.6% or lower and FFP and PLT wastage rates were 0.5% or
      lower. Among the bottom-performing 10% of participants (10th percentile and
      below), expiration rates were 13.8% or higher and wastage rates were 6.8% or
      higher. We were unable to associate selected hospital characteristics or blood
      bank practices with lower rates of FFP and PLT utilization. CONCLUSIONS: The
      rates of FFP and PLT expiration and wastage vary greatly among hospitals in the
      United States. Hospital blood bank personnel are capable of achieving FFP and PLT
      expiration and wastage rates below 1%.

PMID- 11958657
TI  - Storage and distribution of pathology digital images using integrated web-based
      viewing systems.
AB  - CONTEXT: Health care providers have expressed increasing interest in
      incorporating digital images of gross pathology specimens and photomicrographs in
      routine pathology reports. OBJECTIVE: To describe the multiple technical and
      logistical challenges involved in the integration of the various components
      needed for the development of a system for integrated Web-based viewing, storage,
      and distribution of digital images in a large health system. DESIGN: An Oracle
      version 8.1.6 database was developed to store, index, and deploy pathology
      digital photographs via our Intranet. The database allows for retrieval of images
      by patient demographics or by SNOMED code information. SETTING: The Intranet of a
      large health system accessible from multiple computers located within the medical
      center and at distant private physician offices. RESULTS: The images can be
      viewed using any of the workstations of the health system that have authorized
      access to our Intranet, using a standard browser or a browser configured with an
      external viewer or inexpensive plug-in software, such as Prizm 2.0. The images
      can be printed on paper or transferred to film using a digital film recorder.
      Digital images can also be displayed at pathology conferences by using wireless
      local area network (LAN) and secure remote technologies. CONCLUSIONS: The
      standardization of technologies and the adoption of a Web interface for all our
      computer systems allows us to distribute digital images from a pathology database
      to a potentially large group of users distributed in multiple locations
      throughout a large medical center.

PMID- 11958658
TI  - MYCC and MYCN oncogene amplification in medulloblastoma. A fluorescence in situ
      hybridization study on paraffin sections from the Children's Oncology Group.
AB  - CONTEXT: Brain tumors are the most common solid tumor in childhood, and
      medulloblastoma is the most common malignant brain tumor in this age group.
      Cytogenetic abnormalities that have been described in childhood medulloblastoma
      include loss of 17p, amplification of MYCC (c-myc), amplification of MYCN (N
      myc), and isochromosome 17q. Data on these tumors indicate that the frequency of
      MYCC amplification is 5% to 10%. Fluorescence in situ hybridization is a powerful
      tool for investigating these features on archival material. OBJECTIVES: To
      determine if intratumoral heterogeneity exists for MYCC and MYCN in
      medulloblastomas and if tumors with amplified MYCC or MYCN exhibit consistent
      histologic patterns. DESIGN: In this fluorescence in situ hybridization study, we
      investigated the frequency and prognostic significance of MYCC and MYCN
      amplification in 77 medulloblastomas derived from the Children's Oncology Group.
      RESULTS: MYCC amplification occurred in only 4 (5.2%) of 77 tumors. The 4
      patients died of clinically aggressive neoplasms within 7 months of diagnosis.
      Similarly, 4 of 77 patients' tumors were found to exhibit MYCN amplification, but
      survival data are incomplete at present, therefore prognostic significance cannot
      be characterized. CONCLUSIONS: These data establish the frequency of MYCC
      amplification in a large cohort of children with medulloblastoma and further
      suggest that MYCC amplification may be a marker of poor prognosis. Intratumoral
      heterogeneity was identified for these oncogenes in that 1 patient's tumor
      exhibited evidence of both MYCN and MYCC amplification, and this patient
      experienced a shortened survival time.

PMID- 11958659
TI  - Pulmonary neuroendocrine carcinomas. A review of 234 cases and a statistical
      analysis of 50 cases treated at one institution using a simple clinicopathologic
      classification.
AB  - CONTEXT: Primary pulmonary neuroendocrine tumors are traditionally classified
      into 3 major types: typical carcinoid (TC), atypical carcinoid (AC), and large
      cell neuroendocrine carcinoma (LC) or small cell neuroendocrine carcinoma (SC).
      Confusion arises frequently regarding the malignant nature of TC and the
      morphologic differentiation between AC and LC or SC. OBJECTIVE: To provide
      clinicopathologic evidence to streamline and clarify the histomorphologic
      criteria for this group of tumors, emphasizing the prognostic implications.
      PATIENTS: To minimize variability in diagnostic criteria and treatment plans, we
      analyzed a group of patients whose diagnosis and treatment occurred at a single
      institution. We reviewed 234 cases of primary pulmonary neuroendocrine tumors and
      thoroughly studied 50 cases of resected tumors from 1986 to 1995. RESULTS: On the
      basis of morphologic characteristics and biologic behaviors of the tumors, we
      agree with many previous investigators that these tumors are all malignant and
      potentially aggressive. Based on our accumulated data, we have modified Gould
      criteria and reclassified these tumors into 5 types: (1) well-differentiated
      neuroendocrine carcinoma (otherwise called TC) (14 cases, with less than 1
      mitosis per 10 high-power fields [HPF] with or without minimal necrosis); (2)
      moderately differentiated neuroendocrine carcinoma (otherwise called low-grade
      AC) (6 cases, with less than 10 mitoses per 10 HPF and necrosis evident at high
      magnification); (3) poorly differentiated neuroendocrine carcinoma (otherwise
      called high-grade AC) (10 cases, with more than 10 mitoses per 10 HPF and
      necrosis evident at low-power magnification); (4) undifferentiated LC (5 cases,
      with more than 30 mitoses per 10 HPF and marked necrosis); and (5)
      undifferentiated SC (15 cases, with more than 30 mitoses per 10 HPF and marked
      necrosis). The 5-year survival rates were 93%, 83%, 70%, 60%, and 40% for well,
      moderately, and poorly differentiated, and undifferentiated large cell and small
      cell neuroendocrine carcinomas, respectively. We found nodal metastasis in 28% of
      TC in this retrospective review, a figure higher than previously recorded.
      CONCLUSION: Using a grading system and terms comparable to those used for many
      years and used for neuroendocrine tumors elsewhere in the body, we found that
      classification of pulmonary neuroendocrine carcinomas as well, moderately, poorly
      differentiated, or undifferentiated provides prognostic information and avoids
      misleading terms and concepts. This facilitates communication between
      pathologists and clinicians and thereby improves diagnosis and management of the
      patient.

PMID- 11958660
TI  - Morphologic criteria for the diagnosis of prostatic adenocarcinoma in needle
      biopsy specimens. A study of 250 consecutive cases in a routine surgical
      pathology practice.
AB  - CONTEXT: The diagnosis of prostate adenocarcinoma in needle core biopsy specimens
      is based on multiple diagnostic criteria and supportive features, most of which
      have been defined mainly from observations in transurethral resection and
      prostatectomy specimens. There is little information on the frequency with which
      diagnostic and supportive features of prostate cancer occur within benign glands.
      The few reports dealing with diagnostic criteria of cancer in needle biopsies
      have been largely confined to analysis of selected cases that posed particular
      diagnostic difficulty. OBJECTIVE: To analyze the frequency with which numerous
      diagnostic or supportive features of prostate cancer occur in an unselected,
      consecutively performed series of 18-gauge prostate needle biopsy specimens.
      DESIGN: Two hundred fifty consecutive 18-gauge prostate needle biopsy specimens
      (150 malignant and 100 benign) were evaluated, using hematoxylin-eosin-stained
      histologic sections. RESULTS: The frequency of the histologic features in
      malignant and benign glands was as follows: prominent nucleoli (94% and 25% of
      malignant and benign specimens, respectively), marginated nucleoli (88% and 7%),
      multiple nucleoli (64% and 0%), blue-tinged mucinous secretions (52% and 0%),
      intraluminal crystalloids (40.6% and 1%), intraluminal amorphous eosinophilic
      material (86.7% and 2%), collagenous micronodules (2% and 0%), glomerulations
      (15.3% and 0%), perineural invasion (22% and 0%), retraction clefting (38.6% and
      7%), and invasion of fat (0.7% and 0%). CONCLUSIONS: Since not all diagnostic or
      supportive features of cancer are evident in any single case of cancer,
      particularly in needle biopsy specimens in which sampling is limited, awareness
      of these data would be helpful in the assessment of small foci of atypical glands
      being considered for cancer.

PMID- 11958661
TI  - Placental transmogrification of the lung is a histologic pattern frequently
      associated with pulmonary fibrochondromatous hamartoma.
AB  - CONTEXT: Placental transmogrification of the lung is a term introduced to
      describe a peculiar histologic pattern characterized by formation of placental
      villuslike structures in the lung parenchyma. It has been reported to occur in
      association with bullous emphysema and lipomatosis. OBJECTIVES: To study the
      relationship between placental transmogrification and pulmonary hamartomas.
      DESIGN AND METHODS: Reports of 38 cases of pulmonary hamartomas during 18 years
      (1982-1999) were reviewed. All histologic slides of these cases were examined for
      the presence of villuslike papillary projections and placenta-like structures.
      Hamartomas with prominent papillary projections or placenta-like structures were
      further investigated to assess the histogenesis and proliferation of epithelial
      and stromal cells. Immunohistochemical analysis was performed on paraffin
      embedded tissue using monoclonal antibodies against Ki-67 and thyroid
      transcription factor 1 (TTF-1) and polyclonal antibodies against c-Kit antigen (a
      stem cell factor receptor/mast cell growth factor receptor) in conjunction with
      Leder stain for naphthol-ASD-chloroacetate esterase. RESULTS: Placental
      transmogrification was identified in 6 of 38 cases of pulmonary
      fibrochondromatous hamartomas. The histologic change consisted of an abundant
      myxoid or edematous fibroadipose stroma with a respiratory epithelial lining,
      resulting in papillary projections that resembled immature placental villi.
      Epithelium lining the papillary projections was positive for TTF-1 (70%-90%) and
      Ki-67 (3%-5%). In contrast, stromal cells were negative for TTF-1 with only rare
      cells immunoreactive for Ki-67. A number of stromal spindle cells and occasional
      cells in epithelium were c-Kit immunoreactive; however, concurrent Leder stain
      demonstrated that these c-Kit-positive cells were mast cells and not stem cells.
      CONCLUSIONS: Placental transmogrification is frequently associated with pulmonary
      fibrochondromatous hamartomas and may be induced by or associated with a
      proliferation of lining epithelial components in the hamartomas. The significance
      of numerous mast cells within stroma of placental transmogrification is unclear
      and their possible role in inducing stromal proliferation needs to be further
      evaluated.

PMID- 11958662
TI  - Altered expression of G1 regulatory proteins in human soft tissue sarcomas.
AB  - CONTEXT: Soft tissue sarcomas constitute a heterogeneous group of tumors for
      which tumorigenesis is not fully understood. Altered cell-cycle regulation may
      underlie the development and/or progression of human malignancies. However, data
      concerning the occurrence of cell-cycle aberrations in soft tissue sarcomas are
      very limited. OBJECTIVES: To detect the abnormal features of cell-cycle
      regulatory proteins in soft tissue sarcomas and to determine the potential role
      of these proteins in clinical behavior. DESIGN: The p53 and Rb-cyclin D pathways
      were investigated by immunohistochemical studies of p53, mdm2, pRb, p16, cyclin
      D1, and cdk4 proteins, respectively. RESULTS: Of the 67 sarcomas analyzed,
      nuclear accumulation of p53 was detected in 25 samples (37%), and overexpression
      of mdm2 was found in 16 samples (24%). Both p53 and mdm2 expression correlated
      with tumor grade. Abnormalities involving the Rb-cyclin D pathway were identified
      in all of the tumors by the altered expression of either pRb (72%) or p16 (94%).
      Fourteen (21%) and 64 (96%) cases demonstrated cyclin D1 or cdk4 expression,
      respectively. Overexpression of cyclin D1 showed an association with pRb and p53.
      There was no correlation between pRb, p16, cyclin D1, or cdk4 and tumor grade or
      relapse. CONCLUSION: Disturbance in the cell-cycle regulatory system involving
      the p53 pathway and the Rb-cyclin D pathway is relatively frequent in soft tissue
      sarcomas and may be a contributing factor in the tumorigenesis of these tumors.
      The alterations in the Rb-cyclin D pathway probably constitute an early event,
      whereas the abnormalities in the p53 pathway seem to be involved in tumor
      progression. It is noteworthy that cyclin D1 may play a key role in linking both
      pathways.

PMID- 11958663
TI  - Lack of HER-2/neu expression in Hodgkin and non-Hodgkin lymphoma.
AB  - OBJECTIVE: Overexpression of HER-2/neu oncoprotein, a tyrosine kinase receptor,
      occurs in a variety of human cancers and has been shown to play a critical role
      in their development. This overexpression is usually associated with poor
      clinical outcome. The significance of HER-2/neu in lymphomas is unknown. The aim
      of this study was to evaluate the expression of HER-2/neu in the malignant
      lymphomas: non-Hodgkin and Hodgkin lymphomas. METHODS: We studied formalin-fixed,
      paraffin-embedded tissue from 50 patients with lymphoma. Forty-two specimens were
      from patients with various types of non-Hodgkin lymphoma, and 8 were from
      patients with Hodgkin lymphoma. HER-2/neu expression was examined by an
      immunohistochemical technique using the HercepTest. RESULTS: None of the
      specimens demonstrated overexpression or even any expression of HER-2/neu.
      Reactive plasma cells showed cytoplasmic staining, which was not found in
      malignant plasma cells from patients with multiple myeloma. CONCLUSIONS: Non
      Hodgkin and Hodgkin lymphomas do not express the HER-2/neu oncoprotein. This
      finding suggests that HER-2/neu does not play a role in these diseases.

PMID- 11958664
TI  - Activated protein C resistance, the factor V Leiden mutation, and a laboratory
      testing algorithm.
AB  - OBJECTIVES: To present the current understanding of factor V Leiden and activated
      protein C resistance, and to propose a laboratory testing algorithm. DATA
      SOURCES: Publications on MEDLINE with the terms factor V Leiden or activated
      protein C resistance through mid 2001, as well as publications in the authors'
      files, were screened for inclusion in this report. STUDY SELECTION: Original
      studies that report a novel finding on testing or clinical features of activated
      protein C resistance or factor V Leiden are included. Data Extraction.-The novel
      or key findings from the selected studies are analyzed. DATA SYNTHESIS: Protein C
      and protein S are the integral components of an anticoagulation pathway that
      limits fibrinogen conversion to fibrin through the degradation of factors Va and
      VIIIa. When factor Va is resistant to degradation by activated protein C, this
      anticoagulation pathway does not operate properly, and patients have an increased
      risk for thrombosis. This report describes the protein C/protein S pathway, the
      significance of activated protein C resistance and the factor V Leiden mutation,
      and the clinical testing used to detect activated protein C resistance and the
      factor V Leiden mutation. A proposed laboratory testing algorithm is also
      provided. CONCLUSIONS: Factor V Leiden is a risk factor for venous thrombosis and
      it is particularly common in white populations. A laboratory testing algorithm is
      proposed.

PMID- 11958665
TI  - Continuous-specimen-flow, high-throughput, 1-hour tissue processing. A system for
      rapid diagnostic tissue preparation.
AB  - CONTEXT: Current conventional tissue-processing methods employ fixation of
      tissues with neutral buffered formalin, dehydration with alcohol, and clearing
      with xylene before paraffin impregnation. Because the time required for this
      procedure is usually 8 hours or longer, it is customary to process tissues in
      automated instruments throughout the night. Although this time-honored method
      continues to serve histology laboratories well, it has a number of shortcomings,
      such as a 1-day delay of diagnosis, the need to batch specimens, the relatively
      large volumes and toxicity of reagents used, and the extent of RNA degradation.
      OBJECTIVE: To describe a rapid new method of tissue processing using a continuous
      throughput technique. Design.-We used a combination of common histologic
      reagents, excluding formalin and xylene, as well as microwave energy, to develop
      a rapid processing method. The effect of this method on the quality of
      histomorphology, histochemistry, immunohistochemistry, and RNA content of
      processed tissue was compared with that of adjacent tissue sections processed by
      the conventional processing technique. We also assessed the impact of this rapid
      processing system on our practice by comparing the turnaround times of surgical
      pathology reports before and after its implementation. RESULTS: The new
      processing method permitted preparation of paraffin blocks from fresh or prefixed
      tissue in about 1 hour. The procedure allowed continuous flow of specimens at 15
      minute intervals. It eliminated the use of formalin and xylene in the processing
      and used considerably lower volumes of other chemical reagents. Histomorphologic,
      histochemical, and immunohistochemical results were comparable to the parallel
      sections prepared by the conventional method. The new technique, however,
      preserved higher quality RNA. Use of the new methodology led to the diagnosis and
      reporting of more than one third of surgical pathology specimens on the same day
      that they were received, as compared to 1% of same-day reporting before the
      implementation of the rapid processing system. CONCLUSION: The quality of
      hematoxylin-eosin, histochemical, and immunohistochemical tissue sections
      provided by the new system is comparable to that obtained following the
      conventional processing method. The new system preserves RNA better than the
      conventional method. It also shortens the processing time to about 1 hour from
      the receipt of fresh or prefixed tissue, eliminates the need for formalin and
      xylene, and reduces the volume of other chemicals. Most importantly, it impacts
      overall patient management by allowing for considerably shorter turnaround times
      for completion of surgical pathology reports.

PMID- 11958666
TI  - Malignant eccrine spiradenoma.
AB  - Malignant transformation of eccrine spiradenoma is extremely rare. We describe
      the case of a 70-year-old man with malignant eccrine spiradenoma of the forearm
      and metastases to the axillary lymph nodes. Surgical excision with adequate
      margins and lymph node dissection was performed. Tamoxifen therapy was instituted
      after obtaining positive immunostaining results for estrogen receptor. After 41
      months of follow-up, there has been no recurrence or distant metastases. Wide
      local excision and close follow-up are crucial in the management of malignant
      eccrine spiradenoma. The role of other therapeutic modalities, including hormonal
      therapy, remains to be determined.

PMID- 11958667
TI  - Plasma cell granuloma of the thyroid.
AB  - Plasma cell granuloma of the thyroid is an uncommon lesion; only 6 cases have
      been reported in the English literature to date. All reported cases occurred in
      women, mostly after the age of 50 years. We report a case of plasma cell
      granuloma of the thyroid in a 46-year-old woman with a 20-year history of
      euthyroid goiter and a positive family history of goiter in 3 close relatives.
      The lesion was composed of sheets of plasma cells involving the entire parenchyma
      that histologically resembled plasmacytoma. Plasmacytoma was excluded by
      demonstration of polyclonal kappa/lambda light chain immunostaining and by lack
      of evidence of clonal bands by polymerase chain reaction for immunoglobulin heavy
      chain gene rearrangement. Similarly, the predominant histologic pattern in all
      previously reported cases is that of marked plasma cell infiltration. A family
      history of thyroid disease (goiter, thyroiditis) was associated with diffuse
      involvement of the thyroid. Prognosis after surgery is excellent, and to our
      knowledge no cases of malignant transformation or recurrence have been described.

PMID- 11958668
TI  - Benign fibrohistiocytoma (xanthomatous variant) of the acromion. A case report
      and review of the literature.
AB  - A number of fibrous lesions involving bone display almost identical histologic
      appearances yet may represent either reactive or neoplastic conditions, resulting
      in a confusing nomenclature and possible diagnostic confusion. We report the case
      of a young man with no significant previous medical history who presented with a
      painful lesion in the left shoulder, which consisted almost entirely of
      xanthomatous material. We discuss the possible differential diagnosis of this
      lesion and why benign fibrous histiocytoma is the preferred terminology for this
      lesion. To our knowledge, this is the first reported case of a benign fibrous
      histiocytoma involving the acromion in an adult.

PMID- 11958669
TI  - Nasal natural killer cell/T-cell lymphoma showing cellular morphology mimicking
      normal lymphocytes.
AB  - We report the autopsy case of a 34-year-old Japanese man with a nasal natural
      killer (NK)-cell/T-cell lymphoma. The patient developed the disease at 32 years
      of age, and a biopsy of the nasopharynx revealed pleomorphic lymphoma cell
      proliferation. Radiotherapy was performed, but the patient eventually died of
      respiratory failure. After radiotherapy, no histologic evidence of malignancy was
      obtained with biopsy materials featuring lymphocytic infiltration. Autopsy
      studies, including in situ hybridization for Epstein-Barr virus-encoded RNA,
      revealed generalized infiltration of normal lymphocyte-like, UCHL-1-positive, and
      Epstein-Barr virus-encoded RNA-positive lymphoma cells. Monoclonal proliferation
      of the Epstein-Barr virus-carrying cells was verified by means of Southern blot
      analysis. Retrospectively, we concluded that the normal lymphocyte-like
      presentation of the lymphoma cells, probably influenced by radiotherapy,
      prevented pathologists from recognizing the lymphoma. The utility of in situ
      hybridization for Epstein-Barr virus-encoded RNA in identification of tumor cells
      is emphasized with respect to the present case.

PMID- 11958670
TI  - False-positive AxSYM cardiac troponin I results in a 53-year-old woman.
AB  - A number of classes of endogenous antibodies, including heterophile, rheumatoid
      factor, and autoantibodies, can interfere with immunoassay measurements of many
      different analytes. Heterophile and rheumatoid factor antibody interferences have
      been described previously for the AxSYM cardiac troponin I assay. Several
      commercial products have been developed to neutralize heterophile antibody
      interferences. We describe a patient with multiple apparently falsely elevated
      cardiac troponin I results that were unique to the AxSYM analyzer. These cardiac
      troponin I results diluted linearly. When treated with 2 different heterophile
      blocking reagents, the magnitudes of the falsely elevated results increased 17-
      and 26-fold, and these results also demonstrated dilution linearity. This
      interfering substance could be removed by passage through an immobilized protein
      A column and by polyethylene glycol precipitation. It does not appear to be a
      classic heterophile antibody, nor is it a paraprotein. Laboratorians must remain
      constantly vigilant for immunoassay interferences that lead to clinically
      significant inaccurate results and must recognize that accepted methods for
      detecting and neutralizing the interference may be ineffective.

PMID- 11958671
TI  - Oncocytoma-like angiomyolipoma. A clinicopathologic and immunohistochemical study
      of 2 cases.
AB  - We report the clinical, pathologic, and immunohistochemical features of an
      unusual tumor of the kidney composed of densely eosinophilic, polygonal
      epithelioid cells. The patients were a 56-year-old woman and a 35-year-old man.
      The renal tumors were discovered during follow-up for breast carcinoma and
      evaluation for abdominal pain, respectively. The tumors closely resembled
      oncocytoma in routine sections, but were negative for epithelial markers and
      positive for HMB-45, a pattern of reactions characteristic of angiomyolipoma. In
      the woman, a single additional microscopic angiomyolipoma was present in the
      renal parenchyma at a distance from the main tumor. Both patients are alive
      without recurrence 7 and 10 years after surgery, respectively. Based on clinical,
      morphologic, and immunophenotypic features, we conclude that these tumors are
      oncocytoma-like angiomyolipomas.

PMID- 11958672
TI  - Gynecomastia with marked cellular atypia associated with chemotherapy.
AB  - Gynecomastia is a common benign male breast disease, which may exhibit mild
      cellular atypia in cytology specimens. However, marked cytologic atypia can be
      seen in gynecomastia superimposed by chemotherapy. The case described in this
      report demonstrated severe cytologic atypia of gynecomastia mimicking carcinoma
      in a patient treated with chemotherapy for acute leukemia. A distinct cytologic
      feature helpful in avoiding the diagnostic error is described, namely, atypical
      cells admixed with bland ductal cells and appearing at a different plane. The
      importance of applying strict diagnostic criteria in breast cytology and clinical
      correlation is also emphasized.

PMID- 11958673
TI  - Colchicine effect in a colonic hyperplastic polyp. A lesion mimicking serrated
      adenoma.
AB  - Colchicine effect has been described recently in gastrointestinal biopsies, where
      it can result in accumulation of metaphase mitoses and epithelial
      disorganization. We describe the case of a colonic hyperplastic polyp with
      colchicine effect from a 52-year-old woman who was receiving colchicine for
      primary biliary cirrhosis. Biopsy of the polyp revealed prominent metaphase
      mitoses and focal loss of nuclear polarity in the surface epithelium, features
      that mimicked a serrated adenoma. Distinguishing between hyperplastic polyp and
      serrated adenoma is important because of the different management implications
      and the increased potential for neoplastic progression in the latter.

PMID- 11958674
TI  - Megakaryocytes mimicking metastatic breast carcinoma.
AB  - False-positive diagnosis of lymph nodes occurs when a benign element in a lymph
      node, or in its capsule, is interpreted as metastatic carcinoma. This report
      describes a patient with breast carcinoma who had megakaryocytes in axillary
      sentinel lymph nodes mimicking metastatic carcinoma. The patient had no history
      of a hematologic disease, and we found no evidence of a concurrent hematopoietic
      disorder. The megakaryocytes were reactive for CD31, CD61, and von Willebrand
      factor, but not for cytokeratin (AE1/AE3). Megakaryocytes should be added to the
      list of benign histologic abnormalities that may simulate metastatic carcinoma in
      a sentinel lymph node.

PMID- 11958676
TI  - The crisis of 'identity' in high modernity.
AB  - The concept of 'identity' is central to much contemporary sociology, reflecting a
      crisis that manifests itself in two ways. Firstly, there is a view that identity
      is both vital and problematic in this period of high modernity. Secondly, while
      this awareness is reflected in sociology, its accounts of identity are
      inconsistent, under-theorized and incapable of bearing the analytical load
      required. As a result, there is an inherent contradiction between a valuing of
      identity as so fundamental as to be crucial to personal well-being, and a
      theorization of 'identity' that sees it as something constructed, fluid,
      multiple, impermanent and fragmentary. The contemporary crisis of identity thus
      expresses itself as both a crisis of society, and a crisis of theory. This paper
      explores the diverse ways in which 'identity' is deployed before turning to case
      studies of its use by Anthony Giddens and Manuel Castells. This strategy
      demonstrates the widespread and diverse concern with identity before exploring
      how problematic it has become, even in the work of two of the world's leading
      sociologists.

PMID- 11958675
TI  - Two isoforms of Saccharomyces cerevisiae glutaredoxin 2 are expressed in vivo and
      localize to different subcellular compartments.
AB  - Glutaredoxin (Grx)2 from Saccharomyces cerevisiae is a member of the two-cysteine
      (dithiol) subfamily of Grxs involved in the defence against oxidative stress in
      yeast. Recombinant yeast Grx2p, expressed in Escherichia coli, behaves as a
      'classical' Grx that efficiently catalyses the reduction of hydroxyethyl
      disulphide by GSH. Grx2p also catalyses the reduction of GSSG by dihydrolipoamide
      with even higher efficiency. Western blot analysis of S. cerevisiae crude
      extracts identifies two isoforms of Grx2p of 15.9 and 11.9 kDa respectively. The
      levels of these two isoforms reach a peak during the exponential phase of growth
      in normal yeast extract/peptone/dextrose ('YPD') medium, with the long form
      predominating over the short one. From immunochemical analysis of subcellular
      fractions, it is shown that both isoforms are present in mitochondria, but only
      the short one is detected in the cytosolic fraction. On the other hand, only the
      long form is prominent in microsomes. Mitochondrial isoforms should represent the
      processed and unprocessed products of an open reading frame (YDR513W), with a
      putative start codon 99 bp upstream of the GRX2 start codon described thus far.
      These results indicate that GRX2 contains two in-frame start codons, and that
      translation from the first AUG results in a product that is targeted to
      mitochondria. The cytosolic form would result either by initiation from the
      second AUG, or by differential processing of one single translation product.

PMID- 11958677
TI  - Risk, sexuality and economy.
AB  - From the mid 1980s onwards HIV/AIDS became a new subject of work reform, with a
      range of experts producing new knowledges on work and the worker in regard to
      HIV/AIDS and workplace organizations putting in place workplace HIV/AIDS policies
      and programmes. To date, much of the discussion in sociology in regard to such
      policies and programmes has focused on the issue of effectiveness and has been
      concerned with making such policy 'better'. In this article however, and with
      particular reference to sexuality, I suggest that such approaches fail to
      register that workplace HIV/AIDS policies concern new conceptualizations of
      worker identities. Specifically, I suggest that such policies may be viewed as
      part of an assemblage of work reforms which are reworking worker identities as
      risk identities. Thus I argue that workplace HIV/AIDS policies and programmes are
      best understood as risk rationalities. Further, I consider the alignment between
      such rationalities and neo-liberal modes of rule, and in particular consider the
      ways in which workplace HIV/AIDS policies render both HIV/AIDS and sexuality
      calculable and governable in terms of notions of risk, self-responsibility and
      self-management.

PMID- 11958678
TI  - Finance organizations, decisions and emotions.
AB  - Analyses of global financial markets are dominated by atomized models of decision
      making and behavioural psychology ('exuberance' or 'panic'). In contrast, this
      paper argues that overwhelmingly, finance organizations rather than 'individuals'
      make decisions, and routinely use emotions in formulating expectations. Keynes
      introduced emotion (business confidence and animal spirits) but in economics,
      emotion remains individualistic and irrational. Luhmann's system theory lies at
      the other extreme, where emotions like trust and confidence are central
      variables, functional in the reduction of complexity in sub-systems like the
      economy. The gap between irrational emotions aggregated to 'herd' behaviour in
      economics, and 'system trust' applied to finance and money as a 'medium of
      communication' in sociology, remains largely unfilled. This paper argues that
      while organizations cannot be said to 'think' or 'feel', they are rational and
      emotional, because impersonal trust, confidence and their contrary emotions are
      unavoidable in decision-making due to fundamental uncertainty. These future
      oriented emotions are prevalent within and between organizations in the financial
      sector, primarily in generating expectations. The dynamic of corporate activities
      of tense and ruthless struggle is a more plausible level of analysis than either
      financial 'manias' in aggregate or 'system trust'.

PMID- 11958679
TI  - Organizational communication and the symbolic construction of police murder
      investigations.
AB  - This paper draws upon a range of empirical data to consider the ways in which
      police murder investigations are symbolically constructed, both within and
      outside of the police organization. It is argued that a range of communicative
      formats serve to produce the activities associated with police murder
      investigations in a way that serves to legitimate the police function to both
      members of the public and police officers alike. A particular emphasis is placed
      upon understanding the connections between informal and formal communications,
      and the instrumental and expressive objectives that variously underpin them.

PMID- 11958680
TI  - Acid House and Thatcherism: noise, the mob, and the English countryside.
AB  - This paper examines why the late 1980s youth subculture Acid House provoked a
      moral panic of the scale and intensity that it did. The subculture is conceived
      as presenting a disruptive presence to Thatcherism as an hegemonic project. The
      terms under which this occurred are examined through the themes of noise, the
      mob, and the disruption of bureaucratic authority. The presence of Acid House
      within the English countryside, and in particular the Home Counties, is situated
      as enhancing the problematic status of the subculture. The scale of measures
      taken against Acid House is related to Thatcherism's 'authoritarian populism'.
      Acid House is located in terms of a history of similar forms of popular cultural
      activity. The coverage of Acid House in The Sun and The Daily Mail, and the
      parliamentary debate around the second reading of the Entertainments (Increased
      Penalties) Act, are drawn upon throughout.

PMID- 11958681
TI  - From disorganized capitalism to transnational fine tuning? Recent trends in wage
      development, industrial relations, and 'work' as a sociological category.
AB  - The disorganization thesis concentrates upon globalization and market dynamics,
      which are believed to trigger the breakdown of any kind of institutional
      structures. The diversity of capitalism approach, by contrast, places much
      emphasis on the persistence of distinct paths of national economies. Referring to
      comparative data from the OECD and other sources it is shown that some variables
      indicate a robustness of national styles of capitalism. Others hint at
      resemblance: e.g. there is a striking synchronization of the overall and sectoral
      wage development, there is a significant decrease in industrial disputes, and the
      class composition tends to become more similar. A move beyond the disorganization
      thesis and diversity of capitalism approach is suggested. Special attention
      should be paid to the profound impacts of transnational institutions and
      knowledge carriers in the form of experts and guidelines.

PMID- 11958682
TI  - 'Sites' of resistance: alternative websites and state-society relations.
AB  - Much attention has been focused on Singapore's attempt to use information
      technology to build a knowledge-based economy. This paper examines the
      implications of the unintended consequences of the Internet in the restructuring
      of state and society relations in Singapore. We use the data on Singapore-based
      and Singapore-related websites to show (a) the diversity of positions expressed
      by civil society organizations, fringe groups and even mainstream segments of
      society; (b) the negotiation process between the state and civil society over
      various rights and how developments in cyber-space have implications for
      'reality'; (c) how censorship and content regulation itself is a more complex
      multi-dimensional process such that while local politics is regulated, the multi
      ethnic character of the resident population has led to greater religious
      tolerance such that religious groups banned in some countries have found a safe
      haven in Singapore and have used the city-state as a strategic Internet node.

PMID- 11958683
TI  - CCR2 and CCR5 genotypes in HIV type 1-infected adolescents: limited contributions
      to variability in plasma HIV type 1 RNA concentration in the absence of
      antiretroviral therapy.
AB  - In HIV-1-infected individuals, plasma viral RNA concentration as well as
      preservation of CD8+ naive T cells can vary by age. Host genetic factors
      previously shown to mediate HIV-1 pathogenesis in adults and children may operate
      differently in HIV-1-infected adolescents. Our PCR-based haplotyping of genetic
      variants at the loci encoding CC (beta) chemokine receptor 2 (CCR2) and CCR5
      revealed nine haplotypes (designated A through G*2) in 179 seronegative and 228
      seropositive adolescent participants from the Reaching for Excellence in
      Adolescent Care and Health (REACH) Study of the Adolescent Medicine and HIV/AIDS
      Research Network. The influence of CCR2-CCR5 haplotypes and genotypes on plasma
      HIV-1 RNA level was assessed in 207 AIDS-free seropositive individuals (mostly
      African-American females) who either did not receive therapy or had discontinued
      therapy for 6-12 months during initial follow-up between 1996 and 1999. The CCR2
      64I-coding haplotype F*2 and the infrequent CCR5 Delta32-bearing haplotype G*2
      had negligible impact on HIV-1 RNA level (p > 0.83) and CD4+ T cell counts (p >
      0.30). In contrast, nine carriers of the E/E genotype had significantly higher (p
      = 0.007) plasma HIV-1 RNA level and slightly reduced CD4+ cell counts (p = 0.15)
      compared with those not carrying E/E or F*2 or G*2. The effect of E/E on HIV-1
      RNA was stronger (p < 0.001) in a multivariable model adjusted for F*2 or G*2 (p
      = 0.45), race (p = 0.23), gender (p = 0.002), age (p = 0.26), and history of
      antiretroviral therapy (p < 0.001). Thus, among the major CCR2-CCR5
      haplotypes/genotypes in chronically infected and predominantly African-American
      adolescents, only the E/E genotype appeared to influence early host-virus
      equilibration.

PMID- 11958684
TI  - Mother-to-child transmission in the United States of subtypes D and A/G human
      immunodeficiency virus type 1.
AB  - In the United States and Western Europe, most human immunodeficiency virus type 1
      (HIV-1) infections are caused by subtype B. We analyzed the nucleotide sequence
      of HIV-1 RNA in plasma samples from 141 children enrolled into PACTG 377, a
      comparative study of several antiretroviral therapy regimens. Phylogenetic
      analysis revealed that two children, both born in the United States, were
      infected with non-B subtypes that are most commonly found in Africa: one with
      subtype D and the other with circulating recombinant form CRF02, an A/G
      recombinant lineage. Viral load assays performed to monitor treatment response
      underestimated the levels of HIV-1 RNA in the child with the A/G recombinant.
      These cases demonstrate mother-to-child transmission of non-B subtypes of HIV-1
      in the United States. Non-B subtypes should be considered in the management of
      HIV-1-infected pregnant women and children to optimize strategies to prevent and
      treat pediatric HIV-1 infection.

PMID- 11958685
TI  - Initiation of HAART in drug-naive HIV type 1 patients prevents viral breakthrough
      for a median period of 35.5 months in 60% of the patients.
AB  - The introduction of potent combinations of antiviral drugs is a major
      breakthrough in the treatment of HIV. We investigated the long-term virologic
      outcome and the development of resistance after initiating highly active
      antiretroviral therapy (HAART) in drug-naive patients in daily clinical practice.
      Twenty-five treatment-naive HIV-1 patients were started on HAART. Fifteen
      patients responded with a drop in viral load below the limit of detection during
      35.5 (interquartile range: 7) months of therapy. In 6 of 10 patients with
      virologic failure, virus with resistance-related mutations against the received
      drugs emerged. Compared with responders (R), nonresponding (NR) patients were in
      a later disease stage at therapy start (p = 0.0089) with lower CD4 cell counts at
      baseline (p = 0.040), and a lower proportion of nonresponders showed protease
      inhibitor (PI) levels above C(min) (p = 0.049). More NR patients showed secondary
      PI mutations at baseline (p = 0.079), and the CCR2-64I coreceptor polymorphism
      was absent among NR patients, compared with 38.5% of R patients displaying CCR2
      64I (p = 0.053), although the differences were not significant. In conclusion,
      starting HAART in antiretroviral drug-naive HIV-infected patients followed in
      daily clinical practice prevented viral breakthrough for up to 44 months in 60%
      of the patients. Virologic failure was associated with the development of
      resistance-related mutations, a later stage of disease at start of therapy and
      lower PI drug levels.

PMID- 11958686
TI  - Recovery of replication-competent HIV type 1-infected circulating monocytes from
      individuals receiving antiretroviral therapy.
AB  - The affect of antiretroviral therapy (ART) on HIV-1 recovery from blood monocytes
      was determined in purified peripheral blood monocyte-derived macrophage (MDM)
      cultures from HIV-1-infected subjects with undetectable plasma viremia or active
      viral replication. Additionally, the association between replication-competent
      HIV-1-infected MDM and neurocognitive status was examined. Fifty-two individual
      with previous AIDS-defining illnesses receiving nucleoside analogues with and
      without protease inhibitors or no ART were followed for up to 1.5 years.
      Detection of plasma viremia significantly correlated with the occurrence of
      infected monocytes. Viral replication was detected in less than 10% of the MDM
      cultures from 23 individuals receiving effective antiretroviral therapy. In
      contrast, approximately 50% of the MDM cultures from 29 individuals with active
      viral replication and evidence of decreased immune function, including all
      individuals with neurocognitive impairment, produced detectable virus indicating
      that a lack of adequate ART results in increased abundance of replication
      competent blood monocytes. Proviral DNA levels were a minimum of 13-fold higher
      in MDM from subjects with active viral replication. The infrequent detection of
      viral DNA in cultures from individuals receiving effective ART suggested low
      levels of circulating monocytes harboring replication-incompetent virus. These
      studies demonstrate that HIV-infected individuals on ART with breakthrough
      viremia have significantly higher levels of circulating infected monocytes, the
      precursors of tissue macrophages.

PMID- 11958687
TI  - Ability to induce p53 and caspase-mediated apoptosis in primary CD4+ T cells is
      variable among primary isolates of human immunodeficiency virus type 1.
AB  - Infection with human immunodeficiency virus type 1 (HIV-1) is associated with
      dramatic depletion of CD4(+) T cells, the major HIV-1-induced pathogenesis.
      Apoptosis has been suggested to play an important role for the T cell depletion
      and a number of mechanisms have been proposed for the apoptosis in T cells. Here,
      we compared the levels for apoptosis induction in primary peripheral blood
      mononuclear cells (PBMCs) among several laboratory strains and primary isolates
      of the HIV-1 subtypes B and E. The results showed that apoptosis in infected
      PBMCs, preferentially in CD4+ T cell population, became detectable around the
      time for virus production by flow cytometric terminal transferase dUTP nick end
      labeling (TUNEL) technique and staining with the nuclear dye Hoechst 33342. The
      abilities to induce apoptosis in PBMCs were highly variable in individual
      isolates. The increase of p53 protein in infected PBMCs, which was initiated
      before virus production, was observed in infected PBMCs and the levels of p53
      protein were almost proportional to the rates of the isolates to induced
      apoptosis. The cells infected and cultured in the presence of Z-VAD-FMK had
      significantly decreased cell mortalities, indicating that activated caspases also
      played a significant role in the apoptosis. Thus, HIV-1-induced apoptosis in
      primary T cells was accompanied by the p53 protein and caspase activation at
      varied levels in primary isolates.

PMID- 11958688
TI  - Virologic risk factors for vertical transmission of HIV type 1 in Puerto Rico.
AB  - HIV-1 vertical transmission in Puerto Rico has decreased significantly due to the
      implementation of antiviral therapy. Several studies have shown that the
      phenotype of the HIV-1 isolates initially recovered from infected infants has
      generally been one that replicates rapidly, infects macrophages, and
      preferentially use the CCR5 coreceptor. Our hypothesis is that viral genotypic
      and phenotypic differences exist between HIV-1 nontransmitter and transmitter
      mothers. Viral DNA samples and virus isolates were analyzed from a Puerto Rican
      perinatal population. Heteroduplex tracking assay (HTA) was performed on DNA
      samples to detect env V3 evolutionary variants and the extent of heterogeneity
      within each sample. HIV-1 C2-V3 variants were cloned from each patient to study
      sequence variation among the groups. Differences in replication kinetics of viral
      isolates in macrophage and GHOST CCR5 cells were analyzed by use of repeated
      measures linear regression analysis. HTA analysis showed that only two
      nontransmitter patient samples showed the presence of evolutionary variants.
      Phylogenetic analysis between maternal-infant pairs showed that transmission of a
      single maternal variant occurred, with the exception of one sample pair. When
      evaluating amino acid sequences from cloned PCR products, nontransmitting mothers
      appear to have a higher number of distinct sequences than both the transmitting
      mothers (p = 0.0410) and the infected infants (p = 0.0315). Analysis of
      replication kinetics indicated that transmitters showed faster replication
      kinetics in GHOST CCR5 cell cultures at 12 days postinfection (p = 0.0434) and 15
      days postinfection (p = 0.0181). In conclusion, viral homogeneity and rapid
      replication kinetics were correlated with vertical transmission.

PMID- 11958689
TI  - Extracellular Nef protein activates signal transduction pathway from Ras to
      mitogen-activated protein kinase cascades that leads to activation of human
      immunodeficiency virus from latency.
AB  - We previously reported that viral antigen expression was markedly up-regulated by
      stimulation with extracellular Nef, similar to the effects of tumor necrosis
      factor (TNF)-alpha and phorbol myristate acetate, in model cells for HIV-1
      latency. In this study, we examined the molecular mechanism of this novel Nef
      function. Flow cytometry revealed specific binding of Nef on the surface of
      latently infected cells. Furthermore, activation of Ras in the cells was detected
      after treatment with Nef, indicating the involvement of Ras in Nef-mediated
      activation of HIV-1 from latency. This was also confirmed by the observations
      that HIV-1 long-terminal repeat-luciferase (LTR-Luc) activity was significantly
      up-regulated by introduction of the active Ras into uninfected cells, and that
      LTR-Luc activity observed in Nef-treated cells was specifically inhibited by
      introduction of a dominant negative Ras. In addition, PD98059 inhibited the
      activation of HIV-1 by Nef, but not by TNF-alpha. Thus, Nef-mediated reactivation
      of HIV-1 in latent model cells occurs by signal transduction from Ras to mitogen
      activated protein kinase cascades.

PMID- 11958692
TI  - Conflict and cooperation in parental care. Proceedings of a workshop. Bernried,
      Germany, 4-7 August 2000.

PMID- 11958690
TI  - Analysis of a primary isolate-like virus from simian and human immunodeficiency
      virus-infected macaque having broad neutralizing activity.
AB  - To investigate the changes of neutralizing antibodies and viruses during simian
      and human immunodeficiency virus (SHIV) infection, we examined the cross
      neutralizing ability of sequential sera from three macaques infected with SHIV,
      NM-3rN, and analyzed the sensitivity of the reisolate to neutralizing antibodies.
      Neutralizing activities of macaques' sera against the parental HIV-1 showed a
      persistent increase. Neutralizing activities were highly strain specific, but the
      spectrum of the neutralizing activity expanded against various clades of primary
      HIV-1s at 3 years after infection in one of the three macaques. The reisolate
      from an NM3-rN-infected macaque at 56 wpi, designated as R4356, was neutralized
      by sera from this macaque at a much lower titer than NM-3rN, even by the sera
      collected 2 years after the reisolation. Sera from macaques that were newly
      infected with R4356 also did not neutralize R4356 despite neutralizing NM-3rN
      strongly. These results suggested that long-term persistent infection with SHIV
      induced neutralizing antibodies with a broad spectrum. However, a virus resistant
      to the neutralizing antibodies emerged in the persistently infected macaque.

PMID- 11958693
TI  - The evolution of avian parental care.
AB  - A stage model traces key behavioural tactics and life-history traits that are
      involved in the transition from promiscuity with no parental care, the mating
      system that typifies reptiles, to that typical of most birds, social monogamy
      with biparental care. In stage I, females assumed increasing parental investment
      in precocial young, female choice of mates increased, female-biased mating
      dispersal evolved and population sex ratios became male biased. In stage II,
      consortships between mating partners allowed males to attract rare social mates,
      provided a mechanism for paternity assessment and increased female ability to
      assess mate quality. In stage III, relative female scarcity enabled females to
      demand parental investment contributions from males having some paternity
      certainty. This innovation was facilitated by the nature of avian parental care;
      i.e. most care-giving activities can be adopted in small units. Moreover, the
      initial cost of care giving to males was small compared with its benefit to
      females. Males, however, tended to decline to assume non-partitionable, risky, or
      relatively costly parental activities. In stage IV, altriciality coevolved with
      increasing biparental care, resulting in social monogamy. Approaches for testing
      behavioural hypotheses are suggested.

PMID- 11958694
TI  - Phylogenetic reconstruction of parental-care systems in the ancestors of birds.
AB  - Due to the controversy surrounding incipient avian parental care, ancestral
      parental care systems were reconstructed in a phylogeny including major extant
      amniote lineages. Using two different resolutions for the basal avian branches,
      transitions between the states no care, female care, biparental care and male
      care were inferred for the most basal branches of the tree. Uniparental female
      care was inferred for the lineage to birds and crocodiles. Using a phylogeny
      where ratites and tinamous branch off early and an ordered character-state
      assumption, a transition to biparental care was inferred for the ancestor of
      birds. This ancestor could be any organism along the lineage leading from the
      crocodile-bird split up to modern birds, not necessarily the original bird. We
      discuss the support for alternative avian phylogenies and the homology in
      parental care between crocodiles and birds. We suggest that the phylogenetic
      pattern should be used as a starting point for a more detailed analysis of
      parental care systems in birds and their relatives.

PMID- 11958695
TI  - Life-history correlates of the evolution of live bearing in fishes.
AB  - Selection for live bearing is thought to occur when the benefits of increasing
      offspring survival exceed the costs of reduced fecundity, mobility and the
      increased metabolic demands of carrying offspring throughout development. We
      present evidence that live bearing has evolved from egg laying 12 times in
      teleost (bony) fishes, bringing the total number of transitions to 21 to 22 times
      in all fishes, including elasmobranchs (sharks and rays). Live bearers produce
      larger offspring than egg layers in all of 13 independent comparisons for which
      data were available. However, contrary to our expectation there has not been a
      consistent reduction in fecundity; live bearers have fewer offspring in seven out
      of the 11 available comparisons. It was predicted that live bearers would have a
      larger body size, as this facilitates accommodation of developing offspring. This
      prediction was upheld in 14 out of 20 comparisons. However, this trend was driven
      by elasmobranchs, with large live bearers in seven out of eight comparisons.
      Thus, while the evolution of live bearing in elasmobranchs is correlated with
      predicted increases in offspring size and adult size, teleost live bearers do not
      have such a consistent suite of life-history correlates. This suggests that
      constraints or selection pressures on associated life histories may differ in
      live-bearing elasmobranchs and teleost fishes.

PMID- 11958696
TI  - Evolutionary transitions in parental care and live bearing in vertebrates.
AB  - We provide the first review of phylogenetic transitions in parental care and live
      bearing for a wide variety of vertebrates. This includes new analyses of both
      numbers of transitions and transition probabilities. These reveal numerous
      transitions by shorebirds and anurans toward uniparental care by either sex.
      Whereas most or all of the shorebird transitions were from biparental care,
      nearly all of the anuran transitions have been from no care, reflecting the
      prevalence of each form of care in basal lineages in each group. Teleost (bony)
      fishes are similar to anurans in displaying numerous transitions toward
      uniparental contributions by each sex. Whereas cichlid fishes have often evolved
      from biparental care to female care, other teleosts have usually switched from no
      care to male care. Taxa that have evolved exclusive male care without courtship
      role reversal are characterized by male territoriality and low costs of care per
      brood. Males may therefore benefit from care through female preference of
      parental ability in these species. Primates show a high frequency of transitions
      from female care to biparental care, reflecting the prevalence of female care in
      basal lineages. In the numerous taxa that display live bearing by females,
      including teleosts, elasmobranchs, squamate reptiles and invertebrates, we find
      that live bearing has always evolved from a lack of care. Although the transition
      counts and probabilities will undoubtedly be refined as phylogenetic information
      and methodologies improve, the overall biases in these taxa should help to place
      adaptive hypotheses for the evolution of care into a stronger setting for
      understanding directions of change.

PMID- 11958697
TI  - Male-only care and classical polyandry in birds: phylogeny, ecology and sex
      differences in remating opportunities.
AB  - It has been argued recently that the combination of male-only parental care and
      classical polyandry in birds is the most interesting and yet the least understood
      of all avian breeding systems. Despite a huge number of hypotheses, careful
      comparative analyses have repeatedly failed to identify consistent ecological
      differences between species showing male-only care and closely related species
      showing other patterns of care. This has led to the suggestion that such analyses
      fail because the crucial differences are between ancient lineages rather than
      between closely related species. Here, therefore, I use comparisons between
      families to test three well-known hypotheses: that male-only care is associated
      with: (i) a low rate of fecundity; (ii) large egg size relative to female size;
      or (iii) female-biased opportunities for remating. Families showing male-only
      care do not differ from families showing female-only care with respect to rate of
      fecundity or relative egg size. There is, however, a significant difference
      between these two groups of families with respect to an index of remating
      opportunities, nesting density. Families showing female-only care nest at high
      density, while those showing male-only care nest at very low density. This is one
      of the first times a consistent ecological correlate has been identified for male
      only care in birds. It suggests that female-only care arises (or persists) in
      families where remating opportunities are abundant for both sexes, whereas male
      only care arises (or persists) in families where remating opportunities are rare
      for both sexes and particularly scarce for males. This in turn suggests that sex
      differences in remating opportunities are the key ecological factor in
      determining male-only care and classical polyandry in birds.

PMID- 11958698
TI  - Intrafamilial conflict and parental investment: a synthesis.
AB  - We outline and develop current theory on how inherent genetic conflicts of
      interest between the various family members can affect the flow of parental
      investment from parents to offspring, and discuss the problems for empirical
      testing that this generates. The parental investment pattern realized in nature
      reflects the simultaneous resolution of all the conflicts between the family
      players. This depends on the genetic mechanism, the mating system and
      reproductive constraints, on whether extra demand by progeny affects current or
      future sibs, and particularly on the behavioural mechanisms underlying demand
      (begging or solicitation) and supply (provision of parental investment by
      parents). The direction of deviation from the optimal parental investment for the
      parent(s) depends on the slope of what we term the 'effect of supply on demand',
      the mechanism that determines how changes in food supply affect begging levels.
      If increasing food increases begging (positive slope), less parental investment
      is supplied than the parental optimum and if increasing food decreases begging
      (negative slope), more parental investment is supplied. The magnitude of
      deviation depends on both the 'effect of supply on demand' and on the 'effect of
      demand on supply' (the mechanism determining how changes in begging affect food
      supply, which always has a positive slope). We conclude that it will often be
      impossible to deduce the extent of underlying conflict by establishing the amount
      of parental investment given relative to the ideal optimum for the parent. Some
      possible directions for future research are discussed.

PMID- 11958699
TI  - A model of the interaction between 'good genes' and direct benefits in courtship
      feeding animals: when do males of high genetic quality invest less?
AB  - Conflict between mates over the amount of parental investment by each partner is
      probably the rule except in rare cases of genetic monogamy. In systems with
      parental care, males may frequently benefit by providing smaller investments than
      are optimal for individual female partners. Females are therefore expected to
      choose males that will provide the largest amounts of parental investment. In
      some species, however, the preferred males provide less care than their rivals.
      Focusing on species in which males invest by feeding their mates, I use a simple
      model to demonstrate the conditions under which males preferred by females may
      have optimal donations that are smaller than those of less-preferred rivals. Pre
      mating female choice may sufficiently bias the perception of mate availability of
      preferred males relative to their rivals such that preferred males gain by
      conserving resources for future matings. Similarly, 'cryptic' biases in favour of
      high-quality ejaculates by females can compensate for smaller than average
      donations received from preferred males. However, post-fertilization cryptic
      choice should not change the optimal donations of preferred males relative to
      their rivals. I discuss the implications of this work for understanding sexual
      selection in courtship-feeding animals, and the relevance of these systems to
      understanding patterns of investment for animals in general.

PMID- 11958700
TI  - Why is mutual mate choice not the norm? Operational sex ratios, sex roles and the
      evolution of sexually dimorphic and monomorphic signalling.
AB  - Biases in the operational sex ratio (OSR) are seen as the fundamental reason
      behind differential competition for mates in the two sexes, and as a strong
      determinant behind differences in choosiness. This view has been challenged by
      Kokko and Monaghan, who argue that sex-specific parental investment, mortalities,
      mate-encounter rates and quality variation determine the mating system in a way
      that is not reducible to the OSR. We develop a game-theoretic model of
      choosiness, signalling and parental care, to examine (i) whether the results of
      Kokko and Monaghan remain robust when its simplifying assumptions are relaxed,
      (ii) how parental care coevolves with mating strategies and the OSR and (iii) why
      mutual mate choice is observed relatively rarely even when both sexes vary in
      quality. We find qualitative agreement with the simpler approach: parental
      investment is the primary determinant of sex roles instead of the OSR, and
      factors promoting choosiness are high species-specific mate-encounter rate, high
      sex-specific mate-encounter rate, high cost of breeding (parental investment),
      low cost of mate searching and highly variable quality of the opposite sex. The
      coevolution of parental care and mating strategies hinders mutual mate choice if
      one parent can compensate for reduced care by the other, but promotes it if
      offspring survival depends greatly on biparental care. We argue that the relative
      rarity of mutual mate choice is not due to biases in the OSR. Instead, we
      describe processes by which sexual strategies tend to diverge. This divergence is
      prevented, and mutual mate choice maintained, if synergistic benefits of
      biparental care render parental investment both high and not too different in the
      two sexes.

PMID- 11958701
TI  - A theoretical analysis of the energetic costs and consequences of parental care
      decisions.
AB  - Should a parent care for its young or abandon them before they reach
      independence? We consider parental care behaviour as an adaptive decision,
      involving trade-offs between current and future reproduction. The condition of
      the parent is expected to influence these trade-offs. Using a dynamic programming
      model we explore how changes in the levels of energetic reserves, and time in the
      season, determine changes in parental care decisions. The novel feature of our
      model is that we have included the possibility of remating within the current
      breeding season in a consistent manner by explicitly modelling the behaviour of
      unmated animals. We show that there may be several fluctuations in the average
      duration of care during the breeding season. We also show that, because of the
      dependence of parental care behaviour on both the condition of the parent and
      time during the breeding season, changing some of the costs of care may increase
      the duration of care during one part of the season and decrease it at another.
      The model also shows that the conditions prevailing for animals with dependent
      offspring can affect the way in which an unmated animal behaves. For example, the
      behaviour of unmated animals may change to compensate (partly) for increases in
      the costs of raising offspring, which are produced at a later date (for example,
      by increasing the duration of foraging between breeding attempts). Overall, the
      model provides a good framework for understanding how various ecological and life
      history variables should influence parental care behaviour during a breeding
      season.

PMID- 11958702
TI  - Relating paternity to paternal care.
AB  - Intuition suggests, to most people, that parents should be selected to care for
      their offspring in relation to how certain they are of being the parents of those
      offspring. Theoretical models of the relationship between parental investment and
      certainty of parentage predict the two to be related only when some other
      assumptions are made, few of which can be taken for granted. I briefly review the
      models and their assumptions, and discuss two kinds of difficulty facing an
      empiricist wishing to test the models. The first is the problem of unmeasured
      (and immeasurable) variables. The second is the problem that even the most
      extensive models do not capture the complexity that can be demonstrated in real
      systems. I illustrate some of these problems, and some qualitative tests of the
      models, with experimental work on a population of the collared flycatcher. My
      conclusion is that although there are some cases where the models have
      qualitative support, we are a long way from understanding whether paternal care
      is commonly adjusted in relation to certainty of paternity.

PMID- 11958703
TI  - A self-consistent approach to paternity and parental effort.
AB  - We review the relationship between optimal parental effort and paternity, and
      emphasize the need for a self-consistent approach. A fundamental consistency
      condition is what we refer to as the conservation of paternity. Every offspring
      has exactly one father. If a male has a paternity of less than unity, then
      another male or other males must have gained the lost paternity. Our approach
      also emphasizes that paternity emerges as the result of interactions between
      males and females. From this viewpoint, if paternity changes it is because some
      aspect of the interaction changes, and the correlation between effort and
      paternity depends on the aspect that has changed. This has implications for
      comparative analyses of paternity. The conclusions that are drawn about the
      correlation between effort and paternity within a population depend on, for
      example, the types of male in the population and how their abilities are
      correlated. It is easy to construct models that predict negative correlations
      between effort and paternity.

PMID- 11958704
TI  - Parental care and adaptive brood sex ratio manipulation in birds.
AB  - Under many circumstances, it might be adaptive for parents to bias the investment
      in offspring in relation to sex. Recently developed molecular techniques that
      allow sex determination of newly hatched offspring have caused a surge in studies
      of avian sex allocation. Whether females bias the primary brood sex ratio in
      relation to factors such as environmental and parental quality is debated.
      Progress is hampered because the mechanisms for primary sex ratio manipulation
      are unknown. Moreover, publication bias against non-significant results may
      distort our view of adaptive sex ratio manipulation. Despite this, there is
      recent experimental evidence for adaptive brood sex ratio manipulation in birds.
      Parental care is a particularly likely candidate to affect the brood sex ratio
      because it can have strong direct effects on the fitness of both parents and
      their offspring. We investigate and make predictions of factors that can be
      important for adaptive brood sex ratio manipulation under different patterns of
      parental care. We encourage correlational studies based on sufficiently large
      datasets to ensure high statistical power, studies identifying and experimentally
      altering factors with sex-differential fitness effects that may cause brood sex
      ratio skew, and studies that experimentally manipulate brood sex ratio and
      investigate fitness effects.

PMID- 11958705
TI  - Adaptive sex allocation in birds: the complexities of linking theory and
      practice.
AB  - We review some recent theoretical and empirical developments in the study of sex
      allocation in birds. The advent of reliable molecular sexing techniques has led
      to a sharp increase in the number of studies that report biased offspring sex
      ratios in birds. However, compelling evidence for adaptive sex allocation in
      birds is still very scant. We argue that there are two reasons for this: (i)
      standard sex allocation models, very helpful in understanding sex allocation of
      invertebrates, do not sufficiently take the complexities of bird life histories
      and physiology into account. Recent theoretical work might bring us a step closer
      to more realistic models; (ii) experimental field and laboratory studies on sex
      allocation in birds are scarce. Recent experimental work both in the laboratory
      and in the field shows that this is a promising approach.

PMID- 11958706
TI  - Parentally biased favouritism: why should parents specialize in caring for
      different offspring?
AB  - 'Parentally biased favouritism' occurs when the two parents differentially care
      for individual offspring or kinds of offspring. Examples in birds include brood
      division and differential investment by the two parents in relation to the size
      or sex of the offspring. This paper uses mathematical models to investigate which
      ideas can, in theory, explain parentally biased favouritism. One previous
      explanation is that the parents differ in their cost of reproduction and that the
      parent who consequently invests least concentrates its care on the more valuable
      offspring. However, a mathematical model predicts the total care given by each
      parent and received by each offspring, not how much each parent cares for each
      offspring, and hence does not explain parentally biased favouritism. Parentally
      biased favouritism towards particular types of offspring can be explained by a
      difference between the parents in the benefits of caring for a given type of
      offspring or in the effort incurred in providing care to a given type of
      offspring, but then it is extreme, with at least one of the parents providing
      care to only one type of offspring. Parentally biased favouritism towards
      particular individual offspring (brood division) can be explained by parent
      offspring conflict or sexual conflict.

PMID- 11958708
TI  - Cheating and the evolutionary stability of mutualisms.
AB  - Interspecific mutualisms have been playing a central role in the functioning of
      all ecosystems since the early history of life. Yet the theory of coevolution of
      mutualists is virtually nonexistent, by contrast with well-developed
      coevolutionary theories of competition, predator-prey and host-parasite
      interactions. This has prevented resolution of a basic puzzle posed by
      mutualisms: their persistence in spite of apparent evolutionary instability. The
      selective advantage of 'cheating', that is, reaping mutualistic benefits while
      providing fewer commodities to the partner species, is commonly believed to erode
      a mutualistic interaction, leading to its dissolution or reciprocal extinction.
      However, recent empirical findings indicate that stable associations of
      mutualists and cheaters have existed over long evolutionary periods. Here, we
      show that asymmetrical competition within species for the commodities offered by
      mutualistic partners provides a simple and testable ecological mechanism that can
      account for the long-term persistence of mutualisms. Cheating, in effect,
      establishes a background against which better mutualists can display any
      competitive superiority. This can lead to the coexistence and divergence of
      mutualist and cheater phenotypes, as well as to the coexistence of ecologically
      similar, but unrelated mutualists and cheaters.

PMID- 11958707
TI  - Clone mixtures and a pacemaker: new facets of Red-Queen theory and ecology.
AB  - Host-parasite antagonistic interaction has been proposed as a potential agent to
      promote genetic polymorphism and to favour sex against asex, despite its twofold
      cost in reproduction. However, the host-parasite gene-for-gene dynamics often
      produce unstable cycles that tend to destroy genetic diversity. Here, we examine
      such diversity destroying coevolutionary dynamics of host and parasite, which is
      coupled through local or global migration, or both, between demes in a
      metapopulation structure. We show that, with global migration in the island
      model, peculiar out-of-phase islands spontaneously arise in the cluster of
      islands converging to a global synchrony. Such asynchrony induced by the
      'pacemaker islands' serves to restore genetic variation. With increasing fraction
      of local migration, spots of asynchrony are converted into loci or foci of spiral
      and target patterns, whose rotating arms then cover the majority of demes. A
      multi-locus analogue of the model reproduces the same tendency toward asynchrony,
      and the condition arises for an advantage of asexual clones over their sexual
      counterpart when enough genetic diversity is maintained through metapopulation
      storage-migration serves as a cheap alternative to sex.

PMID- 11958709
TI  - Reaction-diffusion models of within-feather pigmentation patterning.
AB  - Feathers are complex, branched keratin structures that exhibit a diversity of
      pigmentation patterns. Feather pigments are transferred into developing feather
      keratinocytes from pigment cells that migrate into the tubular feather germ from
      the dermis. Within-feather pigment patterns are determined by differential
      pigmentation of keratinocytes within independent barb ridges during feather
      development. Little is known about the molecular mechanisms that determine which
      keratinocytes receive pigment. We apply reaction-diffusion models to the growth
      of within-feather pigment patterns based on a realistic model of feather growth.
      These models accurately simulate the growth of a diversity of the within-feather
      pigmentation patterns found in real feathers, including a central patch, a
      'hollow' central patch, concentric central patches, bars, chevrons, a central
      circular spot, rows of paired spots, and arrays of offset dots. The models can
      also simulate the complex transitions between distinct pigmentation patterns
      among feathers observed in real avian plumages, including transitions from bars
      to chevrons, bars to paired dots, and bars to arrays of dots. The congruence
      between the developmental dynamics of the simulated and observed feather patterns
      indicates that the reaction-diffusion models provide a realistic and accurate
      description of the determination of pigment pattern within avian feather
      follicles. The models support the hypothesis that within-feather pigmentation
      patterning is determined by antagonistic interactions among molecular expression
      gradients within the tubular follicle and feather germ.

PMID- 11958710
TI  - Bantu language trees reflect the spread of farming across sub-Saharan Africa: a
      maximum-parsimony analysis.
AB  - Linguistic divergence occurs after speech communities divide, in a process
      similar to speciation among isolated biological populations. The resulting
      languages are hierarchically related, like genes or species. Phylogenetic methods
      developed in evolutionary biology can thus be used to infer language trees, with
      the caveat that 'borrowing' of linguistic elements between languages also occurs,
      to some degree. Maximum-parsimony trees for 75 Bantu and Bantoid African
      languages were constructed using 92 items of basic vocabulary. The level of
      character fit on the trees was high (consistency index was 0.65), indicating that
      a tree model fits Bantu language evolution well, at least for the basic
      vocabulary. The Bantu language tree reflects the spread of farming across this
      part of sub-Saharan Africa between ca. 3000 BC and AD 500. Modern Bantu
      subgroups, defined by clades on parsimony trees, mirror the earliest farming
      traditions both geographically and temporally. This suggests that the major
      subgroups of modern Bantu stem from the Neolithic and Early Iron Age, with little
      subsequent movement by speech communities.

PMID- 11958711
TI  - Visualizing patterns of craniofacial shape variation in Homo sapiens.
AB  - The geometric morphometric analysis of shape variation in complex biological
      structures such as the human skull poses a number of specific challenges: the
      registration of homologous morphologies, the treatment of bilateral symmetry, the
      graphical representation of form variability in three dimensions and the
      interpretation of the results in terms of differential growth processes. To
      visualize complex patterns of shape change, we propose an alternative to
      classical Cartesian deformation grids in the style of D'Arcy W. Thompson.
      Reference to the surface structures of the organism under investigation permits a
      comprehensive visual grasp of shape change and its tentative interpretation in
      terms of differential growth. The application of this method to the analysis of
      human craniofacial shape variation reveals distinct modes of growth and
      development of the neurocranial and viscerocranial regions of the skull. Our data
      further indicate that variations in the orientation of the viscerocranium
      relative to the neurocranium impinge on the shapes of the face and the cranial
      vault.

PMID- 11958712
TI  - Immune response and virus population composition: HIV as a case study.
AB  - Based on the current understanding of the immune response, we present what we
      believe to be a new model of intrahost virus dynamics. The model takes into
      account the relationship between virus replication rate and the level of antigen
      displayed by infected cells, and shows how the cell-directed immune response
      controls both virus load and virus replication rate. In contrast to conventional
      wisdom, it shows that the predominant virus variant does not necessarily have the
      highest replication rate. A strong immune response produces a selective advantage
      for latent viruses, whereas a deteriorating immune response invites in viruses of
      higher replication rates. The model is analysed in light of the well-studied
      HIV/AIDS disease progression, and shows how a wide range of major, seemingly
      unrelated issues in the study of HIV may be accounted for in a simple and unified
      manner.

PMID- 11958713
TI  - Basal metabolic rate and the evolution of the adaptive immune system.
AB  - Vertebrates have evolved an adaptive immune system in addition to the ancestral
      innate immune system. It is often assumed that a trade-off between costs and
      benefits of defence governs the evolution of immunological defence, but the costs
      and benefits specific to the adaptive immune system are poorly known. We used
      genetically engineered mice lacking lymphocytes (i.e. mice without adaptive, but
      with innate, immunity) as a model of the ancestral state in the evolution of the
      vertebrate immune system. To investigate if the magnitude of adaptive defence is
      constrained by the energetic costs of producing lymphocytes etc., we compared the
      basal metabolic rate of normal and lymphocyte-deficient mice. We found that
      lymphocyte-deficient mice had a higher basal metabolic rate than normal mice with
      both innate and adaptive immune defence. This suggests that the evolution of the
      adaptive immune system has not been constrained by energetic costs. Rather, it
      should have been favoured by the energy savings associated with a combination of
      innate and adaptive immune defence.

PMID- 11958714
TI  - Testosterone promotes paternal behaviour in a monogamous mammal via conversion to
      oestrogen.
AB  - Although high testosterone (T) levels inhibit paternal behaviour in birds
      breeding in temperate zones many paternal mammals have a very different breeding
      biology, characterized by a post-partum oestrus. In species with post-partum
      oestrus, males may engage in T-dependent behaviours such as aggression and
      copulation simultaneously with paternal behaviour. We previously found that T
      promotes paternal behaviour in the California mouse, Peromyscus californicus. We
      examine whether this effect is mediated by the conversion of T to oestradiol
      (E(2)) by aromatase. In the first experiment, gonadectomized males treated with T
      or E(2) implants showed higher levels of huddling and pup grooming behaviour than
      gonadectomized males treated with dihydrotestosterone or empty implants. In the
      second experiment, we used an aromatase inhibitor (fadrozole) (FAD) to confirm
      these results. Gonadectomized males treated with T + vehicle or E(2) + FAD showed
      higher levels of huddling and pup grooming behaviour than gonadectomized males
      treated with T + FAD or empty implants. Although E(2) is known to promote the
      onset of maternal behaviour to our knowledge our results are the first to
      demonstrate that E(2) can promote paternal behaviour in a paternal mammal. These
      results may explain how mammals express paternal behaviour while T levels are
      elevated.

PMID- 11958715
TI  - Eye size in birds and the timing of song at dawn.
AB  - Why do different species of birds start their dawn choruses at different times?
      We test the hypothesis that the times at which different species start singing at
      dawn are related to their visual capability at low light intensities. Birds with
      large eyes can achieve greater pupil diameters and hence, all other things being
      equal, greater visual sensitivity and resolution than birds with small eyes. We
      estimated the maximum pupil diameter of passerine birds by measuring the diameter
      of the exposed eye surface, and measured the times of the first songs at dawn of
      songbirds present in different bird communities, and the light intensities at
      these times. Using phylogenetic comparative analyses, we found that songbirds
      with large eyes started to sing at lower light intensities (and therefore
      earlier) than species with smaller eyes. These relationships were stronger when
      differences in body size were controlled for statistically, and were consistent
      between two phylogenies and when species were treated as independent data points.
      Our results therefore provide robust support for the hypothesis that visual
      capability at low light levels influences the times at which birds start to sing
      at dawn.

PMID- 11958716
TI  - Complete mitochondrial DNA genome sequences show that modern birds are not
      descended from transitional shorebirds.
AB  - To test the hypothesis put forward by Feduccia of the origin of modern birds from
      transitional birds, we sequenced the first two complete mitochondrial genomes of
      shorebirds (ruddy turnstone and blackish oystercatcher) and compared their
      sequences with those of already published avian genomes. When corrected for rate
      heterogeneity across sites and non-homogeneous nucleotide compositions among
      lineages in maximum likelihood (ML), the optimal tree places palaeognath birds as
      sister to the neognaths including shorebirds. This optimal topology is a re
      rooting of recently published ordinal-level avian trees derived from
      mitochondrial sequences. Using a penalized likelihood (PL) rate-smoothing process
      in conjunction with dates estimated from fossils, we show that the basal splits
      in the bird tree are much older than the Cretaceous-Tertiary (K-T) boundary,
      reinforcing previous molecular studies that rejected the derivation of modern
      birds from transitional shorebirds. Our mean estimate for the origin of modern
      birds at about 123 million years ago (Myr ago) is quite close to recent estimates
      using both nuclear and mitochondrial genes, and supports theories of continental
      break-up as a driving force in avian diversification. Not only did many modern
      orders of birds originate well before the K-T boundary, but the radiation of
      major clades occurred over an extended period of at least 40 Myr ago, thus also
      falsifying Feduccia's rapid radiation scenario following a K-T bottleneck.

PMID- 11958717
TI  - Song predicts immunocompetence in male European starlings (Sturnus vulgaris).
AB  - According to the immunocompetence handicap hypothesis, sexually selected
      characteristics predict immune function and this relationship is mediated by
      testosterone. In the present study, we investigated whether bird song could
      predict immunity in European starlings (Sturnus vulgaris). We recorded the
      singing and reproductive behaviours of 16 adult male starlings in an outdoor
      aviary and then assessed their cell-mediated and humoral immunity in vivo. The
      males were observed in groups of four for 2 h each day over a 4-day period. For
      each male, the number of songs produced was recorded and the average song-bout
      length was computed. Next, cell-mediated and humoral immunity were assessed via
      cutaneous swelling responses to the T-cell mitogen phytohaemagglutinin and
      antibody responses to a novel antigen, keyhole limpet haemocyanin. Song rate and
      song-bout length were positively correlated with cell-mediated and humoral
      immunity, respectively. Additionally, a negative relationship between plasma
      testosterone concentration and antibody response was observed. These data
      demonstrate that male starling song can be used as a predictor of
      immunocompetence, with more robust singers exhibiting enhanced immunity. Whether
      this relationship is mediated directly by testosterone requires further
      investigation.

PMID- 11958718
TI  - Chemosignalling of musth by individual wild African elephants (Loxodonta
      africana): implications for conservation and management.
AB  - Elephants have extraordinary olfactory receptive equipment, yet this sensory
      system has been only minimally investigated in wild elephants. We present an in
      depth study of urinary chemical signals emitted by individual, behaviourally
      characterized, wild male African elephants, investigating whether these compounds
      were the same, accentuated, or diminished in comparison with captive individuals.
      Remarkably, most emitted chemicals were similar in captive and wild elephants
      with an exception traced to drought-induced dietary cyanates among wild males. We
      observed developmental changes predominated by the transition from acids and
      esters emitted by young males to alcohols and ketones released by older males. We
      determined that the ketones (2-butanone, acetone and 2-pentanone, and 2-nonanone)
      were considerably elevated during early musth, musth and late musth,
      respectively, suggesting that males communicate their condition via these
      compounds. The similarity to compounds released during musth by Asian male
      elephants that evoke conspecific bioresponses suggests the existence of species
      free 'musth' signals. Our innovative techniques, which allow the recognition of
      precise sexual and musth states of individual elephants, can be helpful to
      managers of both wild and captive elephants. Such sampling may allow the more
      accurate categorization of the social and reproductive status of individual male
      elephants.

PMID- 11958719
TI  - Delayed prezygotic isolating mechanisms: evolution with a twist.
AB  - Assortative mating characterizes the situation wherein reproducing individuals
      pair according to similarity. Usually, the impetus for this bias is attributed to
      some type of mate choice conferring benefits (e.g., increased fitness or genetic
      compatibility) and, thereby, promoting speciation and phenotypic evolution. We
      investigate, by computer simulation of an evolving deme-structured snail
      population, the ramifications ensuing from passive assortative mating wherein
      couples exhibiting opposite shell coil direction phenotypes experience a physical
      constraint on mating success: putative mating partners inhabiting stout dextral
      and sinistral shells are unable to exchange sperm. Because shell coil chirality
      genotype is encoded at a single locus by shell coil alleles that are inherited
      maternally, snails containing sinistral alleles can present the typical dextral
      phenotype. Consequently, the incidence of a sinistral allele in as few as one
      snail can be manifested as prezygotic reproductive isolation within a deme in a
      subsequent generation. However, because the efficacy of achieving this type of
      prezygotic reproductive isolation is affected by shell form, the likelihood and
      product of single-gene speciation should be determined by deme interaction
      (migration) and composition (morphological distribution). We test this hypothesis
      and show how stochastic migration interacts with passive assortative mating
      yielding morphologically induced prezygotic reproductive isolation to produce new
      species phenotypes. The results show that demes can achieve rapid macroscopic
      phenotypic transformation and indicate that sympatric speciation might be more
      plausible than naturalists recognize conventionally.

PMID- 11958720
TI  - Bateman's principle and immunity.
AB  - The immunocompetence handicap hypothesis (ICHH) of Folstad and Karter has
      inspired a large number of studies that have tried to understand the causal basis
      of parasite-mediated sexual selection. Even though this hypothesis is based on
      the double function of testosterone, a hormone restricted to vertebrates, studies
      of invertebrates have tended to provide central support for specific predictions
      of the ICHH. I propose an alternative hypothesis that explains many of the
      findings without relying on testosterone or other biochemical feedback loops.
      This alternative is based on Bateman's principle, that males gain fitness by
      increasing their mating success whilst females increase fitness through longevity
      because their reproductive effort is much higher. Consequently, I predict that
      females should invest more in immunity than males. The extent of this dimorphism
      is determined by the mating system and the genetic correlation between males and
      females in immune traits. In support of my arguments, I mainly use studies on
      insects that share innate immunity with vertebrates and have the advantage that
      they are easier to study.

PMID- 11958721
TI  - Effects of divided attention and word concreteness on correct recall and false
      memory reports.
AB  - Lists of thematically related words were presented to participants with or
      without a concurrent task. In Experiments 1 and 2, respectively, English or
      Spanish word lists were either low or high in concreteness (concrete vs abstract
      words) and were presented, respectively, auditorily or visually for study. The
      addition of a concurrent visual or auditory task, respectively, substantially
      reduced correct recall and doubled the frequency of false memory reports
      (nonstudied critical or theme words). Divided attention was interpreted as having
      reduced the opportunity for participants to monitor successfully their
      elicitations of critical associates. Comparisons of concrete and abstract lists
      revealed significantly more recalls of false memories for abstract than concrete
      word lists. Comparisons between two levels of attention, two levels of word
      concreteness, and two presentation modalities failed to support the "more is
      less" effect by which enhanced correct recall is accompanied by increased
      frequencies of false memories.

PMID- 11958722
TI  - Why misinformation is more likely to be recognised over time: A source monitoring
      account.
AB  - Although memory for actual events tends to be forgotten over time, memory for
      misinformation tends to be retrieved at a stable rate over long delays or at a
      rate greater than that found immediately after encoding. To examine whether
      source monitoring errors contribute to this phenomenon, two experiments
      investigated subjects' memory for the source of misinformation at different
      retention intervals. Subjects viewed a slide presentation, read a narrative
      containing misinformation, and, either 10 minutes or 1 week later, completed a
      recognition test about details seen in the slides and about the source of these
      details. After the longer retention interval in both experiments, participants
      were more likely to agree that they had seen misleading information and were also
      more likely to incorrectly associate the misinformation with the slide event.
      Theoretical implications of these findings are considered.

PMID- 11958723
TI  - Source monitoring in a generative task.
AB  - Following exposure to experimenter-provided examples of space creatures, people
      tend to conform to the features contained in the examples when creating their own
      novel space creatures. In three experiments, we manipulated factors known to
      affect source-monitoring accuracy to determine how these manipulations would
      influence conformity to experimenter-provided examples. In Experiment 1 we
      altered people's cognitive agenda by means of the instructions given before the
      drawing task. In Experiment 2 we examined how time pressure would affect the
      level of conformity, and in Experiment 3 we manipulated the availability of the
      creatures during the drawing task by making them available to half the
      participants. Conformity decreased when extended source-monitoring processes were
      engaged and increased when these processes were disrupted. The results from the
      three experiments were consistent with the principles of the source-monitoring
      framework.

PMID- 11958724
TI  - Auditory memory and the irrelevant sound effect: Further evidence for changing
      state disruption.
AB  - Four experiments investigate the hypothesis that irrelevant sound interferes with
      serial recall of auditory items in the same fashion as with visually presented
      items. In Experiment 1 an acoustically changing sequence of 30 irrelevant
      utterances was more disruptive than 30 repetitions of the same utterance (the
      changing-state effect; Jones, Madden, & Miles, 1992) whether the to-be-remembered
      items were visually or auditorily presented. Experiment 2 showed that two
      different utterances spoken once (a heterogeneous compound suffix; LeCompte &
      Watkins, 1995) produced less disruption to serial recall than 15 repetitions of
      the same sequence. Disruption thus depends on the number of sounds in the
      irrelevant sequence. In Experiments 3a and 3b the number of different sounds, the
      "token-set" size (Tremblay & Jones, 1998), in an irrelevant sequence also
      influenced the magnitude of disruption in both irrelevant sound and compound
      suffix conditions. The results support the view that the disruption of memory for
      auditory items, like memory for visually presented items, is dependent on the
      number of different irrelevant sounds presented and the size of the set from
      which these sounds are taken. Theoretical implications are discussed.

PMID- 11958725
TI  - On the role of item similarity in retrieval-induced forgetting.
AB  - We report on two experiments designed to examine how the similarity of retrieval
      practised and not-retrieval-practised items influences the amount of retrieval
      induced forgetting. Participants studied categorised item lists with each
      category consisting of exemplars from two different semantic subcategories. Using
      both the retrieval practice paradigm (Experiment 1) and the output interference
      paradigm (Experiment 2) we found that the retrieval of a subset of the studied
      items impaired the subsequent recall of the nonpractised items if the two types
      of items were fairly dissimilar to each other (same category but different
      subcategory) but did not induce impairment if the two types of items were highly
      similar (same category and subcategory). These results indicate that a high
      degree of similarity of practised and nonpractised items can eliminate retrieval
      induced forgetting. They also suggest that forgetting in the retrieval practice
      paradigm and forgetting in the output interference paradigm are mediated by the
      same mechanisms. The relation of the present results to other very recent
      findings about the role of item similarity in retrieval-induced forgetting in
      discussed.

PMID- 11958726
TI  - ALS and motor neuron disorders today and tomorrow.

PMID- 11958727
TI  - Neural transplantation therapy: trying the tougher experiment.

PMID- 11958728
TI  - Intraspinal implantation of hNT neurons into SOD1 mice with apparent motor
      deficit.
AB  - INTRODUCTION: The aim of this study was to determine the effect of hNT neuron
      transplants on motor neuron function in SOD1 (G93A) mice when motor deficits were
      already apparent. METHOD: The hNT neurons were implanted into L(4)-L(5) segments
      of the ventral horn spinal cord of mice at 15-16 weeks of age: either G93A mice,
      transgenic mice carrying the normal allele for human SOD1 gene (hTg), or control
      wild type mice (wt). Behavioral tests (rotorod, beam balance, extension reflex,
      footprint) were performed prior to transplantation and at weekly intervals
      afterwards. RESULTS: HNT neuron transplantation in the SOD1 mice delayed disease
      progression for 3-4 weeks, although lifespan was not affected. CONCLUSION: These
      results suggest that hNT neuron transplantation may be a promising therapeutic
      strategy for ALS in the later phase of the neurodegeneration.

PMID- 11958729
TI  - Lasting impact in families after death from ALS.
AB  - INTRODUCTION: ALS severely affects families, who have to cope after the patient's
      death. There is no information on ongoing needs or concerns of families surviving
      the death of the ALS patient. We wished to survey these needs. METHOD: We
      developed a written questionnaire which we distributed at a single point in time
      to 32 patients' families. All patients had been followed in the McMaster
      University ALS clinic, and had died months to years earlier from ALS. RESULTS:
      The response rate was excellent (85%). ALS caused lasting emotional and financial
      hardship in families, and 37% of respondents felt they were coping poorly,
      sometimes years after the patient's death. This did not clearly relate to the
      bereavement period, nor to the physical or financial impact of the disease during
      life. In most cases the disease led to a strengthening of family ties. However,
      15% of chief caregivers felt blamed by in-laws for contributing to the death of
      the patient; in these cases family ties weakened. Less than half of families were
      still receiving ALS information, although 75% still wished to. About two-thirds
      of families had ongoing questions about the disease, and a small number remained
      concerned that they, or their children, would develop the disease. Only a third
      of families were actively involved in ongoing fund-raising activities.
      CONCLUSIONS: It is possible to survey ongoing family needs after the death of the
      ALS patient. ALS causes lasting impact in surviving family members. There are
      ongoing needs that could be met by ALS clinics, ALS organizations, and healthcare
      systems, and opportunities for greater involvement of family members in volunteer
      activities, awareness, and fundraising. Generalization across other healthcare
      systems, and comparison with other disease states, could be important.

PMID- 11958730
TI  - Masseter inhibitory reflex in amyotrophic lateral sclerosis.
AB  - OBJECTIVES: To elucidate underlying abnormalities of the masseter motor system in
      amyotrophic lateral sclerosis (ALS). METHODS: We recorded biphasic EMG
      suppressions of the masseter muscle (silent or inhibitory periods 1 and 2) after
      electrical stimulation of the mental nerve during maximum clenching of the teeth
      in 16 ALS patients and 15 healthy control subjects. We also examined the recovery
      cycle of the silent periods by delivering paired stimuli with an interstimulus
      interval of 250 ms. RESULTS: Silent period 1 in the patients was not
      significantly different from that in control subjects, whereas silent period 2
      (as measured by its area on the graph) was increased in the patients, especially
      with exaggerated jaw jerk. Only two patients showed absence of silent period 2.
      The recovery cycle of silent period 2 in the subgroup of patients with
      exaggerated jaw jerk was significantly lower than the control value. CONCLUSIONS:
      The abnormalities of the masseter inhibitory reflex in ALS could be ascribable to
      involvement of the corticobulbar or corticoreticular tract projecting to the
      inhibitory interneurons mediating silent period 2.

PMID- 11958731
TI  - Measuring mental health in amyotrophic lateral sclerosis (ALS): a comparison of
      the SF-36 Mental Health Index with the Psychological General Well-Being Index.
AB  - OBJECT: The purpose of this study was to compare the performance of the five-item
      mental health dimension of SF-36 (the Mental Health Index, MHI-5) with that of
      the 22-item Psychological General Well-Being Index (PGWB) in patients presenting
      with amyotrophic lateral sclerosis/motor neuron disease, using tests of
      reliability and validity. DESIGN: A questionnaire-based survey of patients
      diagnosed with ALS across 15 European countries. SAMPLE: Patients presenting at
      neurological clinics for treatment of their ALS were asked to join the survey.
      RESULTS: 1048 patients with ALS have been recruited, of whom 861 (82.2%) have
      returned baseline questionnaires. There was evidence supporting the internal
      consistency of both instruments, and for their construct validity in
      distinguishing between groups, in terms of gender and age. The scores on the two
      instruments were highly correlated (Spearman rank correlation 0.85). CONCLUSION:
      Both the MHI-5 and the PGWB showed high levels of construct validity and internal
      reliability in this patient group. The MHI-5 has comparable psychometric
      performance to the PGWB, and can be used to measure and compare mental health in
      defined populations.

PMID- 11958732
TI  - The ALS Patient Care Database: insights into end-of-life care in ALS.
AB  - OBJECTIVE: To study clinical practices and patient outcomes near the end of life
      in amyotrophic lateral sclerosis (ALS). BACKGROUND: Patients, families, and
      healthcare providers face several dilemmas in selecting and delivering care near
      the end of life in ALS. Published data on clinical practices and their benefits
      during end-of-life care for ALS patients consist of anecdotal reports based on
      small case series or individual case reports. METHODS: Data were obtained from
      1014 American and Canadian patients with ALS who died while participating in a
      large observational registry (the ALS Patient Care Database) during the past four
      years. Following death, a caregiver or family member provided data for each
      patient using a standard questionnaire. Data were principally generated through
      American and Canadian ALS multidisciplinary centers of excellence. RESULTS: Most
      patients died peacefully (90.7%) and 62.4% died in a hospice-supported
      environment. Advance directives were in place for 88.9% of patients and were
      followed in 96.8%. Among the 67 patients who exhibited distress in the dying
      process, symptoms included breathing difficulties (82.1%), fear/anxiety (55.2%),
      pain (23.9%), insomnia (14.9%), and choking (14.93%). Oxygen was given to 52.6%
      of patients, and pain medications were given to 74%. CONCLUSION: These data
      suggest that palliative care at the end of life was relatively well managed for
      most patients with ALS who participated in this study; nevertheless, several
      opportunities for improvement were identified.

PMID- 11958733
TI  - Ventilatory support in Japan: a new life with ALS and a positive approach to
      living with the disease.

PMID- 11958734
TI  - Requiem for chromones?

PMID- 11958735
TI  - IgG subclasses serum concentrations in a population of children with Down
      syndrome: comparative study with siblings and general population.
AB  - Serum total IgG and subclasses were determined in three different groups of
      children: with Down syndrome, their siblings and general pediatric population.
      Several cases of IgG2 and IgG4 deficiency were identified, predominantly in
      children with Down syndrome. The differences, considering three age groups, were
      statistically significant for both groups in relation to the general population
      group, with an increase of IgG1 and IgG3 and a decrease in serum concentrations
      of IgG2 and IgG4. Down syndrome children and their siblings tend o have a similar
      variation of the IgG4 serum concentration levels (P < 0.05). The mechanisms of
      this concordance are not well understood. The results point out that an adequate
      strategy to improve the immune status of Down syndrome children could have a
      positive manifestation in the immune profile of their brothers.

PMID- 11958736
TI  - Specific immune response to Parietaria judaica plant profilin: a low T cell
      proliferative response supports high IgE and skin prick test.
AB  - BACKGROUND: allergic disease caused by Parietaria judaica (Pj) has been widely
      documented in Mediterranean area. Profilins have been identified as widely
      distributed allergenic proteins. The role of Pj profilin in specific immune
      response in Pj-sensitized patients is unknown. METHODS: skin prick test and
      determination of specific and total IgE levels in serum were performed in all
      patients (n = 28) and non-allergic controls (n = 18). Peripheral blood
      mononuclear cells (PBMC) were isolated from both groups and stimulated with crude
      extract or highly purified Pj profilin. The production of type I and type II
      cytokines was determined by specific and polyclonal stimuli in patients and
      controls. T-cell lines specific to Pj profilin were established and cross
      reactivity with another highly purified profilin from Phleum pratense (Phl p) was
      evaluated. RESULTS: Pj profilin-sensitized patients showed a small but
      significantly increased in T-cell proliferative response to this profilin
      compared with non-atopic controls. The production of interleukin (IL)-4 and
      interferon (IFN)-&#947; in response to the specific stimulus was undetectable.
      However, the production of IL-4 in response to a polyclonal stimulus
      [phytohemagglutinin (PHA)] was significantly higher in atopic patients than in
      controls. The T-cell response did not correlate with the magnitude of response to
      skin prick tests with Pj profilin or with Pj-specific serum IgE levels. In
      addition, the production of IL-4 in response to a polyclonal stimulus (PHA) did
      not correlate with the individual skin prick tests to Pj profilin or with Pj
      specific IgE levels in serum. The T-cell lines tested showed no cross-reactivity
      with Phl p profilin. CONCLUSIONS: our results suggest that Pj profilin is partly
      responsible for the T-cell-mediated response in patients allergic to Pj. The high
      skin reactivity to Pj profilin is these patients was accompanied by a small
      increase in the T-cell response to this profilin. The response was highly
      specific since Pj profilin specific T-cell lines showed no cross-reactivity with
      a highly homologous profilin from Phl p. The lack of correlation between the
      proliferative T-cell response and polyclonal IL-4 production with allergen
      specific serum IgE and skin reactivity probably indicates that some of the
      responding T-cells may be involved in immune reactions other than those
      supporting IgE production.

PMID- 11958737
TI  - Pulmonary functions in atopic and nonatopic asthmatic children.
AB  - BACKGROUND: we examined how lung function and certain clinical and laboratory
      characteristics in asthmatic children were changed according to skin test
      positivity to aeroallergens. METHODS: a skin prick test was conducted using
      standardized extracts of 10 different allergens in 56 children with bronchial
      asthma, aged 5-15 years, in Dicle University Hospital. Lung function was measured
      by Microplus spirometer. RESULTS: among the 56 subjects, asthma was classified as
      mild in 16, moderate in 42 and severe in 3. At least one skin prick test was
      positive (monosensitized) in 35 subjects (62 %) and positive reactivity to two or
      more aeroallergens (polysensitized) was found in 17 subjects (30 %). Positive
      skin test reactions to aeroallergens were associated with a decrease (as
      percentage of the predicted decrease) in FEV1, FVC and PEF values. Significant
      differences were also found between prick test-positive and -negative asthmatics
      in duration of breastfeeding (8.5 5 months vs 15 7 months, respectively, p <
      0.007), age at which cow's milk had been started (5.7 1.6 vs 10.5 5.4, p =
      0.004); total serum IgE concentration (350 221 IU/ml vs 234 164 IU/ml, p = 0.02),
      age at onset of asthma symptoms (2.5 1.9 years vs 4.1 2.2 years) and number of
      asthma attacks per year (7.0 3.1 vs 5.2 3.5, p = 0.012). When one-way ANOVA and a
      post-Hoc test were used, asthma attacks were more frequent and severe and
      allergic conjunctivitis symptoms were more frequent in the polysensitized group
      than in the nonsensitized and monosensitized groups (p = 0.03). CONCLUSIONS:
      children with positive skin prick test results, especially those with combined
      sensitivity to dust mite, cat and dog, were at increase risk of more severe
      asthma.

PMID- 11958738
TI  - Relationship of clinical and aerobiological pollen data in the north-west of
      Spain.
AB  - BACKGROUND: few studies report clinical and aerobiological pollen data in the
      north-west of Spain, a region similar to northern and central Europe. Moreover,
      it is difficult to obtain patients' collaboration in filling out symptom cards.
      The aim of this study was to establish a relationship between pollen types and
      clinical data obtained through questionnaire and telephone calls. PATIENTS AND
      METHODS: from January to December 2000, 24 patients aged 28 10.6 years and
      allergic to pollens were studied. The seasonal and hourly rhythm of symptoms and
      their intensity were obtained monthly by telephone calls. Atmospheric pollen was
      collected over the same period using a Hirst-type volumetric pollen sampler.
      RESULTS: the most important pollen types recorded were Poaceae, Betula,
      Parietaria and Plantago. Most patients (83 %) showed symptoms during March and in
      the period between May and July (99 %), which coincided with the greatest
      quantity of atmospheric pollen. Fifty-six percent of the patients complained of
      symptoms during the first hours of the morning, 63 % during the central hours of
      the day and 22 % at nightfall. In specific sensitizations, symptoms were more
      evident during the hours of maximum atmospheric levels of their taxa.
      CONCLUSIONS: the method employed in the present study to obtain information on
      patients' symptomatology (telephoning their homes once a month) proved useful and
      revealed a clear relationship between the presence of certain pollens in the
      atmosphere and the development of symptoms.

PMID- 11958739
TI  - Lipoprotein profile in long term theophylline administration in children with
      asthma.
AB  - Atherosclerosis in childhood has a slowly progressive course and its clinical
      features usually become prominent in middle ages. Hypercholesterolemia is one of
      the major risk factors for the development of atherosclerosis. A clear
      correlation exists between hypercholesterolemia in childhood and atherosclerotic
      lesions extending into adulthood.In this study, we evaluated the effect of slow
      release theophylline (SRT) treatment on plasma lipid profile and assessed the
      risk for atherosclerotic coronary heart disease in children with bronchial
      asthma. Group 1 consisted of 15 children with a mean age of 10.8 3.19 years who
      received SRT for bronchial asthma for a mean period of 9.13 2.17 months. Group 2
      was composed of 15 children with a mean age of 11.40 3.78 years and followed up
      for bronchial asthma, who received no SRT treatment. Group 3 comprised 15
      children with a mean age of 9.00 3.76 years and no history of asthma or wheezing.
      In all patients lipid profiles were assessed by measuring levels of plasma
      triglyceride, total cholesterol, high density lipoprotein cholesterol (HDL-C),
      low density lipoprotein cholesterol (LDL-C) apolipoprotein A (Apo-A) and
      apolipoprotein B (Apo-B). In group 1, the mean total cholesterol level was 175.53
      24.36 mg/dl, LDL-C level was 91.00 24.07 mg/dl and Apo-B level was 87.27 12.74
      mg/dl after SRT treatment. In group 1, group 2 (control group with asthma) and
      group 3 (the non-asthmatic control group), the mean plasma lipid level after SRT
      treatment was significantly higher than that before SRT treatment. In conclusion,
      long-term SRT treatment in children with bronchial asthma may alter lipid profile
      and may increase the risk for developing atherosclerotic coronary heart disease.

PMID- 11958741
TI  - Omalizumab. A review of the new treatment of allergic asthma and seasonal
      allergic rhinitis.
AB  - The causal role of immunoglobulin E (IgE) in triggering the cascade of
      biochemical events leading to allergic disease is well established. Treatments
      that selectively inhibit IgE activity are a logical approach in managing the
      allergic response. Omalizumab is a recombinant humanised monoclonal antibody
      which specifically binds to the Cepsilon3 domain of immunoglobulin (Ig) E, the
      site of high-affinity IgE receptor binding. The clinical benefit and steroid
      sparing effect of treatment with the anti-immunoglobulin-E (IgE) antibody,
      Omalizumab, was assessed in patients with moderate-to-severe allergic asthma and
      seasonal allergic rhinitis. Intravenous and subcutaneous administration of anti
      IgE mAb reduces circulating levels of IgE in atopic patients to low levels
      commonly seen in non-atopic individuals. Anti-IgE therapy offers protection
      against allergen-induced bronchoconstriction, reduces the need for short acting
      inhaled beta 2-agonist and corticosteroids among asthmatic patients and reduces
      severity of symptoms of allergic rhinitis. Adverse events were infrequent in
      clinical trials of omalizumab, and not significantly different from placebo. The
      most frequent drug-related event was mild to moderate urticaria. They do not
      induce anaphylaxis and the occurrence of antibodies against anti-IgE mAb is
      sporadic. The results of cited studies suggest that humanized anti-IgE monoclonal
      antibodies may have important immunotherapeutic benefit for treatment of allergic
      disorders.

PMID- 11958740
TI  - Influence in the quality of life of the respiratory patients by environmental
      control and the acaricide Frontac(r).
AB  - The present prospective, open, observational study assessed the effect of the use
      of standard environmental control measures together with the application of an
      acaricide-containing aerosol of esbiol/benzyl benzoate/piperonyl butoxide/2
      phenylphenol (Frontac) on several clinical and environmental parameters in
      patients suffering from perennial allergic rhinoconjunctivitis related to house
      dust mites (HDM). Fifty-five patients were enrolled and studied for one year.
      Both symptoms and the patients' quality of life (evaluated by the
      Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)) were assessed at
      several clinic visits. The amount of HDM antigen was semi-quantitatively
      estimated using the guanine test. We found a significant decrease (p < 0.001) in
      most nasal symptoms scores: sneezing, runny nose, stuffy nose and itching. The
      overall quality of life (QoL) score also showed a significant improvement during
      the study period; the mean score decrease found was 0.86 (CI 95 %, 0.54-1.17) (p
      < 0.001). Five of the seven domains included in the questionnaire decreased
      significantly: non-hayfever symptoms; practical problems; nasal symptoms; eye
      symptoms, and emotions. These QoL score decreases were found during the first 3
      months and later remained stable at lower levels than at baseline. The content of
      guanine in dust samples decreased significantly from 2.17 0.75 to 1.43 0.68 (p <
      0.001). No toxic adverse events were recorded. In conclusion, these results show
      an improvement in the quality of life and a clinical benefit of the long-term use
      of the new chemical acaricide tested, together with environmental measures, in
      the home of patients suffering from allergic respiratory pathology.

PMID- 11958742
TI  - Barnacle hypersensitivity.
AB  - BACKGROUND: the aim of the present study is to investigate the responsible
      mechanism of different adverse reactions suffered by five patients, aged between
      six and thirty years-old, after consumption of barnacle. The symptoms were
      angioedema, dyspnea, generalized urticaria, conjunctivitis and one of them
      suffered from anaphylactic reaction. Four patients had personal atopic history.
      METHODS: the allergic study included prick by prick test with raw and boiled
      barnacle and prick-test with a standardized battery of shellfish and
      neumoallergens, specific-IgE determination to barnacle, crustacean and house-dust
      mite and SDS-PAGE immunoblotting to barnacle. Even though an oral challenge was
      proposed to three of the patients, they were reluctant to do the test and
      eventually the challenges were not carried out. RESULTS: prick to prick tests
      were positive to barnacle for all of them. Specific-IgE was found in four
      patients. The western blotting results showed an IgE-binding band whose apparent
      molecular mass ranged between 58 and 68 kDa. CONCLUSIONS: barnacle could induce
      IgE-mediated adverse reaction. Our study has demonstrated the presence of an IgE
      binding protein in barnacle extracts ranged between 58 and 68 kDa of molecular
      mass. It has not been previously described a crustacean allergen with the same
      molecular mass, so it could be a specific allergen from barnacle. We believe that
      further study will confirm this is the case.

PMID- 11958743
TI  - Allergy to pine nut.
AB  - BACKGROUND: food allergy is highly prevalent in our environment, especially among
      atopic patients. Pinus pinea is common in our region and its fruit, the pine nut,
      is allergologically important. Several cases have been reported in the literature
      that demonstrate the existence of common antigenic bands between pine nut and
      almond. In this study we try to assess this finding and the possible existence of
      common allergens by in vitro techniques. METHODS AND RESULTS: we present a 10
      year-old boy, previously diagnosed of seasonal rhinoconjunctivitis with
      sensitisation to grass and olive pollen, who had an anaphylactic reaction after
      eating pine nut. We performed in vivo (prick test, prick-by-prick) and in vitro
      tests (total and specific IgE determinations [CAP-FEIA]), histamine release test,
      and immunoblotting (SDS-PAGE). We also reviewed the literature through the
      MEDLINE database in PubMed. CONCLUSIONS: because pine nut is commonly consumed in
      our environment, the prevalence of allergic reactions is probably considerable
      and these reactions take place at an early age. We demonstrate the existence of
      common antigenic proteins between pine nut and peanuts.

PMID- 11958744
TI  - [The new national regulation on Legionella: between ambition and reality].

PMID- 11958745
TI  - [Antibiotics as growth promoters in animals. Are we going down the right road?].

PMID- 11958746
TI  - ["Collective imaginary": lyricism in public health].

PMID- 11958747
TI  - [Requests for HIV tests and their performance in primary health care. Study of
      the Sentinel Physician Network of Castilla y Leon in Spain, 1990-1996].
AB  - AIM: To describe the patterns of requests for and the carrying out of the HIV
      test in Primary Health Care and the epidemological characteristics of the
      individuals who have undergone the test. METHOD: A retrospective descriptive
      study of requests for the HIV test in Primary Health Care, in the area covered by
      the Sentinel Network of Castile and Leon between 1991 and 1996. The validity of
      the results was assured through an initial study of geographical representativity
      and populational diversity, with periodical adjustments. The information was
      obtained through weekly reports from Sentinel doctors. RESULTS: The request rate
      per 100.000 inhabitants showed a tendency to increase until 1993, levelling off
      in 1995 and 1996. There were significant differences between percentage of test
      requested by doctors (55.9%) and patients (40%), as well as between males/females
      and average for age of these. Of the 63.1% of patients with known risk factor:
      17.5% were injected drug users (IDUs) and 11.2% were through unsafe heterosexual
      contact; these factors being modified over time. The predominant risk factors
      among males were: heterosexual contact (31.1%) and the use of injected drugs
      (27.9%). The case was similar for females: 22.7% and 6.9% respectively. The
      results were positive in 3.2% of the HIV tests. CONCLUSIONS: An increase in
      requests and tests carried out between 1991 and 1993 was detected. The figures
      later stabilized and, in general, they were lower than in other studies. The
      doctor was predominantly the origin of the request. A decrease in IDUs and an
      increase in the percentage of unsafe heterosexual contact, were detected, both in
      line with data from other research. Primary Health Care had a predominant place
      in early detection of risk practice and in the areas of prevention, education and
      information.

PMID- 11958748
TI  - [Prevalence of drug utilization in the adult population of Catalonia, Spain].
AB  - OBJECTIVES: To describe the prevalence of drug utilization according to
      sociodemographic factors and self-perceived health in the adult population.
      METHODS: Cross-sectional health survey of the CRONICAT/MONICA-Catalonia study
      carried out in 1994-96 in a random sample of the general population aged 25-64
      years. A total of 3,421 participants (72% response rate) were interviewed about
      drug consumption in the previous two weeks with an open questionnaire. The
      participants were also asked about other health habits. Drugs were subsequently
      classified according to the ATC classification (1993 version). RESULTS: A higher
      proportion of women (38%) than men (26%) self-perceived poor health status (p <
      0.001). Age-adjusted total drug utilization was 57% in men (95%CI: 55-59) and 76%
      in women (95%CI: 74-78). Excluding contraceptives, regular drug utilization was
      35% in men (95%CI: 33-37) and 48% in women (95%CI: 46-51). Twenty-nine percent of
      men and 48% of women (p < 0.001) took more than one drug. Neither educational
      level nor marital status influenced drug utilization. Among men, drug consumption
      was higher in retired individuals and pensioners (68%; 95%CI: 62-74) than in
      active workers (54%; 95%CI: 52-57). The most frequently used drugs were those for
      the nervous system (35% men and 51% women; p < 0.001), alimentary tract (15%) and
      the cardiovascular system (9% and 13%; p < 0.001). Most drugs (40%) were
      prescribed by specialists and one quarter was self-prescribed. CONCLUSIONS: The
      prevalence of total drug utilization in the adult population of Catalonia is
      high, specially among women, who self-perceived worse health status. Policies of
      rationalization of drug expenditures should take the epidemiological pattern into
      account.

PMID- 11958749
TI  - [Factors associated with smoking and the intention to smoke in secondary school
      pupils: results of the ESFA project in Barcelona, Spain].
AB  - OBJECTIVE: To describe the factors asssociated with smoking and intention to
      smoke among a representative sample of first-grade pupils of secondary education
      (12-13 years old) in Barcelona. SUBJECTS AND METHODS: 37 secondary schools were
      randomly selected to evaluate the impact of a European-wide smoking prevention
      program (European Smoking prevention Frame Approach, ESFA project). In these
      schools, 1041 pupils of first grade of secondary education responded to a
      questionnaire designed at the University of Maastricht to study life-style
      attitudes and behaviours, mainly smoking. RESULTS: 9.8% of boys and 12.6% of
      girls declared to smoke either regulary or ocasionally. Among the no-smokers,
      61.4% of the boys and 73.3% of the girls reported to have the intention to smoke
      in the future. Among the boys, factors associated with smoking included social
      norms (odds ratio [OR] = 2.5; 95% confidence interval [CI]: 1.2-5.2), smoking by
      siblings (OR = 2.4; 95% CI, 1.1-5.2), attitudes against smoking (OR = 0.3; 95%
      CI, 0.1-0.6), practicing some sports in the leisure time (OR = 0.3; 95% CI, 0.1
      0.7) and having more available pocket money (OR = 3.2; 95% CI, 1.5-6.8).
      Intention to smoke was only related to attitudes (OR = 0.3; 95% CI, 0.2-0.5).
      Among girls, smoking was associated to perceived pressure to smoke (OR = 2.5; 95%
      CI, 1.2-5.0), consumption by friends (OR = 6.0; 95% CI, 2.4-15.4) and attitudes
      against smoking (OR = 0.2; 95% CI, 0.1-0.4), while intention was only associated
      to attitudes (OR = 0.4; 95% CI, 0.2-0.6) and hanging out in the street in the
      leisure time (OR = 2.2; 95% CI, 0.3-3.5). CONCLUSIONS: The results stress the
      need to deal simultaneoulsy with the different factors associated to smoking
      initiation and attitude shaping, including cognitive factors, environmental
      factors, and patterns of leisure time utilization.

PMID- 11958750
TI  - [Use of emergency medical service and sociodemographic factors].
AB  - OBJECTIVES: Health resources utilization is related to health conditions and to
      the population's sociodemographic characteristics. Low socioeconomic groups show
      increased utilization of certain resources. Emergency department utilization
      could also be affected by socioeconomic factors. The aim of this study was to
      identify differences in emergency department utilization among different
      socioeconomic groups. MATERIAL AND METHODS: A population-based study was
      performed. Census sections of the city of Santander in Spain were grouped
      according to sociodemographic variables (age, educational and professional
      attinment). Areas of the city with similar socioeconomic characteristics were
      established by cluster analysis. The place of residence of patients visiting the
      emergency department of th Hospital Marques de Valdecilla was identified and the
      utilization rate was calculated for each cluster. RESULTS: Cluster analysis was
      able to identify four different groups, each with different socioeconomic
      characteristics, which were closely related to the districts of Santander.
      Comparison of clusters 1 and 4 showed that increased emergency department
      utilization was found amongst groups with lowest socioeconomic status and higher
      mean age, with an odds ratio of 1.91 (95% CI: 1.73-2.1). Patients from higher
      socioeconomic groups were more likely to be admitted to hospital while those from
      lower socioeconomic groups made more repeat visits to the emergency department.
      CONCLUSION: Emergency department utilization is affected by the sociodemographic
      characteristics of patients' area of residence. Patients with lower socioeconomic
      status show greater use of the emergency department.

PMID- 11958751
TI  - [Vertical integration and contracting-out in generic hospital services in Spain].
AB  - OBJECTIVES: This study examines the factors that influence make or buy decisions
      corresponding to four generic services (housekeeping, laundry, food services, and
      maintenance and security) in Spanish hospitals (3,160 transactions in 790
      hospitals). METHODS: The empirical estimation of a logistic model based on
      hospital utility maximization is presented. Factors included in the model are not
      only those related to transaction costs, but also those related to public
      intervention and the political dimension. RESULTS: A total of 55.7% of hospitals
      contracted-out at least one of the generic services. The services most frequently
      contracted-out were housekeeping and maintenance and security(45.1 and 32.5%,
      respectively). In contrast, the services (94.3% and 80.1%, respectively).
      Hospital size (economies of scale), measured by the number of beds, was one of
      the most important factors influencing make or buy decisions. CONCLUSIONS: We
      find evidence that economies of scale are related to a higher level of vertical
      integration, while specialization and for-profit objectives favor the decision to
      contract-out. The choice of organizational model for laundry services presents a
      different pattern from that of the other three services. Empirical results show
      that some asset specificity could be present in laundry services.

PMID- 11958752
TI  - [Increase in hospital services utilization by persons aged 55 years or older:
      population ageing and response of the health system].
AB  - OBJECTIVES: To examine changes in hospital service utilization between 1985 and
      1994 in Spain and Andalucia and to estimate the proportion of change due to
      population ageing. METHODS: The increase in hospitalization rates between 1985
      and 1994 was calculated. Expected hospital discharges in 1994, were calculated by
      multiplying hospital discharge rates in 1985 by the population in 1994 for each
      age group. RESULTS: Between 1985 and 1994 hospitalization rates increased among
      persons aged 55 years old order. The increase ranged from 20.01% (55-64 years
      old) to 52% (more than 75 years old). The percentage of this increase due to
      population ageing was slight (range: 2.8 to 14.8%). CONCLUSIONS: The increase in
      hospitalization rates among persons aged 55 years old or older is only partially
      explained by population ageing, which can be attributed to supply and demand of
      services.

PMID- 11958753
TI  - Correspondence analysis of the Spanish National Health Survey.
AB  - This report gives a comprehensive explanation of the multivariate technique
      called correspondence analysis, applied in the context of a large survey of a
      nation's state of health, in this case the Spanish National Health Survey. It is
      first shown how correspondence analysis can be used to interpret a simple cross
      tabulation by visualizing the table in the form of a map of points representing
      the rows and columns of the table. Combinations of variables can also be
      interpreted by coding the data in the appropriate way. The technique can also be
      used to deduce optimal scale values for the levels of a categorical variable,
      thus giving quantitative meaning to the categories. Multiple correspondence
      analysis can analyze several categorical variables simultaneously, and is
      analogous to factor analysis of continuous variables. Other uses of
      correspondence analysis are illustrated using different variables of the same
      Spanish database: for example, exploring patterns of missing data and visualizing
      trends across surveys from consecutive years.

PMID- 11958754
TI  - [Alternatives to pharmaceutical distribution and reimbursement].
AB  - In Spain pharmaceutical distribution is carried out mainly thorugh the 20,000
      independent pharmacies located throughout the country. This situation contrasts
      with that in other countries where other health care providers play a major role
      in drug dispensation or where pharmacies form part of industrial conglomerates or
      commercial chains. We describe the pharmaceutical distribution chain in Spain
      wholesale and through the pharmacies and place particular emphasis on five
      aspects of relevance when considering alternatives: ownership of the pharmacy and
      norms of professional service, criteria for setting up a pharmacy, monopoly on
      dispensing, automatic ageement with the Spanish national health system and
      reimbursement system. Several alternatives found in comparable countries are
      described: mail order and on-line distribution, sale of over-the counter
      pharmaceutical products in establishments other than pharmacies, the
      estabilishment of pharmaceutical chains, dispensing by providers, the
      repercussions of electronic prescribing and the possibilities of the still
      emerging Pharmacuetical Care. The characteristics of pharmacy reimbursement
      systems are also reviewed. We recommend modification of limitations on ownership
      of pharmacies, the establishment of optional agreements between pharmacies and
      the Spanish national health system and the authorization of alternative or
      complementary channels of distribution for some products. We propose a mixed
      model of reimbursement that would include: a) a ficed price for dispensing; b)
      almost total return of the cost of the product; c) reimbursement for services
      explicity defined by the financer, and d) the possibility of a selective fixed
      payment for certain situations depending on the agreed services or a guaranteed
      minimum income.

PMID- 11958755
TI  - [Research and the recent evolution of primary health care].
AB  - Primary care in Spain has undergone a burgeoning phase in the 80's, followed by a
      decade of stagnation in the 90's, with little creativity, a routinisation of
      tasks, and the set up of service port-folios and program-contracts. On the other
      hand, the recent changes in the orientation of the research promoted by the
      health administration, in favor of basic research, at the expense of health
      services research and clinical epidemiology, are in contrast with the importance
      of primary care as a natural setting for the management of many causal agents and
      risk factors for health. Despite such limitations, the culture of research has
      become present in many primary care centres and pharmacies, and primary care
      research is increasingly present in scientific journals. Nevertheless, it is
      necessary, also for the case of primary care, to manage research, in
      differentiated and specific ways, favoring priorization, evaluation and
      responsibility through flexible organisational formulas and information systems.
      This should include contracting procedures allowing for at least part-time
      research, as well as professional career models acknowledging research and
      teaching activities. Scientific and professional associations in primary care
      face the challenge of maintaning research projects, of increasing their presence
      among professionals, of formulating opinions regarding the problems of their
      sector, as well as of reinforcing their organizational and communication
      capabilities.

PMID- 11958756
TI  - [Application of tobit regression models in modelling censored epidemiological
      variables].
AB  - Many variables in epidemiological studies are continuous measures obtained by
      means of measurement equipments with detection limits, generating censored
      distributions. The censorship, opposite to the trucation, takes place for a
      defect of the data of the sample. The distribution of a censored variable is a
      mixture between a continuous and a categorical distributions. In this case,
      results from lineal regression models, by means of ordinary least squares, will
      provide biased estimates. With one only censorhip point the tobit model must be
      used, while with several censorship points this model's generalization should
      also be used. The illustration of these models is presented through the analysis
      of the levels of mercury measured in urine in the study about health effects of a
      municipal solid-waste incinerator in the county of Mataro (Spain).

PMID- 11958757
TI  - [Your dignity is everyone's dignity].

PMID- 11958758
TI  - [Rational prescribing in patients with arterial hypertension].

PMID- 11958760
TI  - [Hypoglycemia insulin test in the assessment of the hypothalamic-pituitary
      adrenal function].
AB  - BACKGROUND: Recent advances in sensitivity and specificity of hormone
      immunoanalysis and their automatization have brought about changes in clinical
      laboratories that led us to review the need for some endocrine dynamic tests. The
      specific aim of this study was to determine the basal cortisol values predicting
      a normal or impaired response to the insulin hypoglycemia test (ITT). SUBJECTS
      AND METHOD: We retrospectively analysed cortisol responses to ITT in 320
      subjects. Moreover, we studied the impact the use of a new strategy has on
      economic cost, by means of a relative value unit (RVU) calculation. RESULTS: No
      patient with a basal cortisol < 6 g/dl (13%) responded to the test whereas all
      those with a basal cortisol > 18 g/dl responded in full. The rest of patients
      exhibited a basal cortisol level between 6-18 g/dl, 39% of them responding and
      16% showing an inadequate response. Baseline and peak cortisol concentrations
      were strongly correlated (r = 0.74; p < 0.0001). The cost of ITT was 131.6 RVU as
      compared to 17.8 RVU for cortisol. CONCLUSIONS: Basal cortisol levels below 6
      g/dl or above 18 g/dl make the test unnecessary. Cortisol measurement by
      automated methods, along with subsequent reduced assay times, allows us to apply
      new diagnosis strategies. Considering that the cost of ITT is 15 fold higher than
      that of single cortisol measurement, the potentially generated saving is
      significant.

PMID- 11958761
TI  - [Effectiveness of inhaled corticosteroids in chronic obstructive lung disease:
      systematic review].
AB  - BACKGROUND: Inhaled corticosteroids are increasingly being used in patients with
      chronic obstructive lung disease (COPD), but their effectiveness is disputed. The
      aim of this study was to define the clinical effectiveness of inhaled
      corticosteroids in non-asthmatic COPD by a systematic review of the literature.
      MATERIAL AND METHOD: Literature searches were conducted in Medline, the Cochrane
      library and the Spanish Medical Index. Only placebo-controlled trials were
      included. All trials were reviewed by two authors and data were extracted in a
      pre-defined manner. Meta-analytic techniques were used to estimate global effects
      when data were comparable. RESULTS: No clinical trials on the role of inhaled
      corticosteroids during COPD exacerbations were found. Twelve studies on patients
      under a stable condition were identified and included in the review. Short-term
      studies showed that inhaled corticosteroids induced a small increase in FEV1
      (average: 96 ml after 1-6 months). Longer term studies indicated that after 1-3
      years of continued therapy, FEV1 was higher in treated than in control patients,
      but the difference was small (51 ml, CI 3-98). There were no consistent effects
      on symptom scores or the frequency of exacerbations. CONCLUSION: The results of
      this review do not support the systematic use of inhaled corticosteroids in
      patients with non-asthmatic COPD.

PMID- 11958762
TI  - [Prevalence of hepatitis C virus in pregnant women and vertical transmission].
AB  - BACKGROUND: The objectives of this study were to know the seroprevalence of HCV
      in pregnant women and to determine its vertical transmission rate as well as the
      viremia evolution in infected children. PATIENTS AND METHOD: Two different
      populations were studied: a) all pregnant women (n = 2,615) controlled in our
      hospital during 1999, and b) newborns (n = 228) to mothers with HCV antibodies
      (Ab) who were referred to our hospital from January 1995 to September 2000.
      Eighty of these infants were born to mothers coinfected with HIV-1. HCV Ab were
      determined by ELISA and RIBA techniques and viral ARN was studied by PCR. Risk
      factors in infected pregnant women were reviewed. RESULTS: HCV Ab were detected
      in 37 women using RIBA or PCR, hence meaning a seroprevalence rate of 1.4%. Usual
      risk factors were not identified in 35% of cases. Median viral load was 3.5 * 105
      IU/ml. ARN HCV was detected in 15 infants, 9 out of them being born to mothers
      coinfected with HIV-1 (vertical transmission rate: 11.25%) and the remaining 6
      being born to mothers without HIV-1 coinfection (vertical transmission rate: 4%).
      The difference in the transmission rate had statistical significance (p < 0.05).
      CONCLUSIONS: Seroprevalence of HCV infection in our population of pregnant women
      was relatively high. HCV screening in pregnant women is useful in order to
      identify this infection not only in this population but also in newborns and,
      consequently, to follow-up the vertical transmission cases.

PMID- 11958763
TI  - [Mortality due to dementias in Catalonia, Spain: an emergent health problem].
AB  - BACKGROUND: The aims of this study were to describe the trends of mortality from
      dementias according to gender and age in Catalonia (Spain) and to estimate their
      evolution from 1979 to 2003. MATERIAL AND METHOD: The dementia death data (ICD-9:
      290-290.9 298.9, 294.9, 331.0, and 331.2) between 1979 and 1998 come from the
      Catalonian Mortality Register of the Department of Health as well as the official
      population census, lineal estimations and projections made by the Institute of
      Statistics of Catalonia. For the calculation of trend and mortality projections
      up to 2003, a Poisson regression model was adjusted for each gender, using the
      variables age, period and birth cohort. RESULTS: Dementia mortality rate moved
      from 2.14 per 100,000 inhabitants during 1979-1983 to 41.95 during 1994-1998.
      With regard to the period 1989-1998, the average percentage of the annual
      variation of mortality is estimated to be 7.5% for males and 9.6% for females.
      The increase is in part due to population aging and also to a cohort effect of
      people born before 1925. The expected annual mean number of dementia deaths
      during 1999-2003 is estimated at 4,594. CONCLUSIONS: Mortality from dementias in
      Catalonia has experienced a substantial increase over the last 20 years. Given
      the health and social impact of this group of diseases and the future
      perspectives, dementias should be considered as an emergent problem in public
      health.

PMID- 11958764
TI  - [Early detection of lung cancer: the right time].

PMID- 11958765
TI  - [European Resuscitation Council Guidelines 2000 for adult advanced life support].

PMID- 11958766
TI  - [Clinical development of antitumoral vaccines].

PMID- 11958767
TI  - [Tetrabamate and a benefit-risk ratio].

PMID- 11958768
TI  - [Data in favor of genetic heterogeneity of the hemochromatosis in the South of
      Europe].

PMID- 11958769
TI  - [Successful autologous peripheral blood stem cell transplantation in a case of
      IgM myeloma].

PMID- 11958770
TI  - [Moral deliberation and counselling].

PMID- 11958771
TI  - Behavior of a GPI-anchored protein in phospholipid monolayers at the air-water
      interface.
AB  - The interaction between alkaline phosphatase (AP), a glycosylphosphatidylinositol
      (GPI)-anchored protein (AP-GPI), and phospholipids was monitored using Langmuir
      isotherms and PM-IRRAS spectroscopy. AP-GPI was injected under C16 phospholipid
      monolayers with either a neutral polar head (1,2-dipalmitoyl-sn-glycero-3
      phosphocholine monohydrate (DPPC)) or an anionic polar head (1,2-dipalmitoyl-sn
      glycero-3-phospho-L-serine (DPPS)). The increase in molecular area due to the
      injection of protein depended on the surface pressure and the type of
      phospholipid. At all surface pressures, it was highest in the case of DPPS
      monolayers. The surface elasticity coefficient E, determined from the pi-A
      diagrams, allowed to deduct that the AP-GPI-phospholipid mixtures presented a
      molecular arrangement less condensed than the corresponding pure phospholipid
      films. PM-IRRAS spectra suggested different protein-lipid interactions as a
      function of the nature of the lipids. AP-GPI modified the organization of the
      DPPS deuterated chains whereas AP-GPI affected only the polar group of DPPC at
      low surface pressure (8 mN/m). Different protein hydration layers between the
      DPPC and DPPS monolayers were suggested to explain these results. PM-IRRAS
      spectra of AP-GPI in the presence of lipids showed a shape similar to those
      collected for pure AP-GPI, indicating a similar orientation of AP-GPI in the
      presence or absence of phospholipids, where the active sites of the enzyme are
      turned outside of the membrane.

PMID- 11958772
TI  - Reversibility of structural rearrangements in the negative vesicular membrane
      upon electrostatic adsorption/desorption of the polycation.
AB  - Interaction of small unilamellar vesicles (SUVs), composed of negative
      diphosphatidylglycerol (cardiolipin, CL(2-)) and neutral
      dipalmitoylphosphatidylcholine (DPPC), with poly(N-ethyl-4-vinylpyridinium
      bromide) (PEVP) was studied in water solution above and below the vesicular
      membrane melting point by means of differential scanning calorimetry, photon
      correlation spectroscopy, microelectrophoresis, conductometry, and fluorescence
      techniques. It has been found that CL(2-) species are homogeneously distributed
      within DPPC-CL(2-) SUV membrane leaflets and between them. Interaction of PEVP
      with DPPC-CL(2-) SUVs led to drastic structural rearrangements in the membrane if
      it was in the fluid state (liquid SUVs). Negative CL(2-) molecules migrated from
      the inner to the outer membrane leaflet and segregated in the vicinity of
      adsorbed PEVP chains. In addition, PEVP adsorption terminated completely the
      exchange of lipid molecules between the SUVs. At the same time, the integrity of
      liquid SUVs contacting PEVP remained unchanged. Since the interaction of PEVP
      with liquid SUVs was predominantly electrostatic in nature, the polycation could
      be completely removed from the vesicular membrane by addition of an excess of
      polyacrylic acid (PAA) polyanions forming a more stable electrostatic complex
      with PEVP. Removal of PEVP resulted in complete resumption of the original
      distribution of lipids in lateral and transmembrane directions as well as
      intervesicular lipid exchange. In contrast, PEVP interacting with DPPC-CL(2-)
      SUVs formed defects in the vesicular membrane if it was in the gel state (solid
      SUVs). Such interaction was contributed not only by electrostatic but most likely
      by hydrophobic interactions involving the defected membrane sites. PEVP kept
      contacting solid SUVs in the presence of an abundant amount of PAA. The
      established phenomena may be important for understanding the biological effects
      of polycations.

PMID- 11958773
TI  - Interference of serum with lipoplex-cell interaction: modulation of intracellular
      processing.
AB  - We have investigated the mechanism of lipoplex-mediated transfection, employing a
      dialkyl pyridinium surfactant (SAINT-2), and using serum as a modulator of
      complex stability and processing. Particle size and stability determine lipoplex
      internalization, the kinetics of intracellular processing, and transfection
      efficiency. Clustered SAINT-2 lipoplexes are obtained in the absence of serum (
      FBS lipoplexes), but not in its presence (+FBS lipoplexes), or when serum was
      present during lipoplex formation [FBS], conditions that mimic potential
      penetration of serum proteins. The topology of DNA in [FBS] lipoplexes shifts
      from a supercoiled, as in -FBS lipoplexes, to a predominantly open-circular
      conformation, and is more prone to digestion by DNase. Consistently, atomic force
      microscopy revealed complexes with tubular extensions, reflecting DNA that
      protrudes from the lipoplex surface. Interestingly, the internalization of [FBS]
      lipoplexes is approximately three-fold higher than that of -FBS and +FBS
      lipoplexes, yet their transfection efficiency is approximately five-fold lower.
      Moreover, in contrast to -FBS and +FBS complexes, [FBS] complexes were rapidly
      processed into the late endosomal/lysosomal degradation pathway. Intriguingly,
      transfection by [FBS] complexes is greatly improved by osmotic rupture of
      endocytic compartments. Our data imply that constraints in size and morphology
      govern the complex' ability to interact with and perturb cellular membranes,
      required for gene release. By extrapolation, we propose that serum may regulate
      these parameters in an amphiphile-dependent manner, by complex 'penetration' and
      modulation of DNA conformation.

PMID- 11958774
TI  - Effects of phosphatidylserine on membrane incorporation and surface protection
      properties of exchangeable poly(ethylene glycol)-conjugated lipids.
AB  - Liposomes containing the acidic phospholipid phosphatidylserine (PS) have been
      shown to avidly interact with proteins involved in blood coagulation and
      complement activation. Membranes with PS were therefore used to assess the
      shielding properties of poly(ethylene glycol 2000)-derivatized
      phosphatidylethanolamine (PE-PEG(2000)) with various acyl chain lengths on
      membranes containing reactive lipids. The desorption of PE-PEG(2000) from PS
      containing liposomes was studied using an in vitro assay which involved the
      transfer of PE-PEG(2000) into multilamellar vesicles, and the reactivity of PS
      containing liposomes was monitored by quantifying interactions with blood
      coagulation proteins. The percent inhibition of clotting activity of PS liposomes
      was dependent on the PE-PEG(2000) content. 1,2-Distearoyl-sn-glycero-3
      phosphoethanolamine (DSPE)-PEG(2000) which transferred out slowly from PS
      liposomes was able to abolish >80% of clotting activity of PS liposomes at 15
      mol%. This level of DSPE-PEG(2000) was also able to extend the mean residence
      time of PS liposomes from 0.2 h to 14 h. However, PE-PEG(2000) with shorter acyl
      chains such as 1,2-dimyristyl-sn-glycero-3-phosphoethanolamine-PEG(2000) were
      rapidly transferred out from PS liposomes, which resulted in a 73% decrease in
      clotting activity inhibition and 45% of administered intravenously liposomes were
      removed from the blood within 15 min after injection. Thus, PS facilitates the
      desorption of PE-PEG(2000) from PS containing liposomes, thereby providing
      additional control of PEG release rates from membrane surfaces. These results
      suggest that membrane reactivity can be selectively regulated by surface grafted
      PEGs coupled to phosphatidylethanolamine of an appropriate acyl chain length.

PMID- 11958775
TI  - Basolateral potassium channels of rabbit colon epithelium: role in sodium
      absorption and chloride secretion.
AB  - In order to assess the role of different classes of K(+) channels in
      recirculation of K(+) across the basolateral membrane of rabbit distal colon
      epithelium, the effects of various K(+) channel inhibitors were tested on the
      activity of single K(+) channels from the basolateral membrane, on macroscopic
      basolateral K(+) conductance, and on the rate of Na(+) absorption and Cl(-)
      secretion. In single-channel measurements using the lipid bilayer reconstitution
      system, high-conductance (236 pS), Ca(2+)-activated K(+) (BK(Ca)) channels were
      most frequently detected; the second most abundant channel was a low-conductance
      K(+) channel (31 pS) that exhibited channel rundown. In addition to Ba(2+) and
      charybdotoxin (ChTX), the BK(Ca) channels were inhibited by quinidine, verapamil
      and tetraethylammonium (TEA), the latter only when present on the side of the
      channel from which K(+) flow originates. Macroscopic basolateral K(+)
      conductance, determined in amphotericin-permeabilised epithelia, was also
      markedly reduced by quinidine and verapamil, TEA inhibited only from the lumen
      side, and serosal ChTX was without effect. The chromanol 293B and the
      sulphonylurea tolbutamide did not affect BK(Ca) channels and had no or only a
      small inhibitory effect on macroscopic basolateral K(+) conductance.
      Transepithelial Na(+) absorption was partly inhibited by Ba(2+), quinidine and
      verapamil, suggesting that BK(Ca) channels are involved in basolateral
      recirculation of K(+) during Na(+) absorption in rabbit colon. The BK(Ca) channel
      inhibitors TEA and ChTX did not reduce Na(+) absorption, probably because TEA
      does not enter intact cells and ChTX is 'knocked off' its extracellular binding
      site by K(+) outflow from the cell interior. Transepithelial Cl(-) secretion was
      inhibited completely by Ba(2+) and 293B, partly by quinidine but not by the other
      K(+) channel blockers, indicating that the small (<3 pS) K(V)LQT1 channels are
      responsible for basolateral K(+) exit during Cl(-) secretion. Hence different
      types of K(+) channels mediate basolateral K(+) exit during transepithelial Na(+)
      and Cl(-) transport.

PMID- 11958776
TI  - Overproduction in yeast and rapid and efficient purification of the rabbit
      SERCA1a Ca(2+)-ATPase.
AB  - Large amounts of heterologous C-terminally his-tagged SERCA1a Ca(2+)-ATPase were
      expressed in yeast using a galactose-regulated promoter and purified by Ni(2+)
      affinity chromatography followed by Reactive red chromatography. Optimizing the
      number of galactose inductions and increasing the amount of Gal4p transcription
      factor improved expression. Lowering the temperature from 28 degrees C to 18
      degrees C during expression enhanced the recovery of solubilized and active
      Ca(2+)-ATPase. In these conditions, a 4 l yeast culture produced 100 mg of Ca(2+)
      ATPase, 60 and 22 mg being pelleted with the heavy and light membrane fractions
      respectively, representing 7 and 1.7% of total proteins. The Ca(2+)-ATPase
      expressed in light membranes was 100% solubilized with L-alpha
      lysophosphatidylcholine (LPC), 50% with n-dodecyl beta-D-maltoside (DM) and 25%
      with octaethylene glycol mono-n-dodecyl ether (C(12)E(8)). Compared to LPC, DM
      preserved specific activity of the solubilized Ca(2+)-ATPase during the
      chromatographic steps. Starting from 1/6 (3.8 mg) of the total amount of Ca(2+)
      ATPase expressed in light membranes, 800 microg could be routinely purified to
      50% purity by metal affinity chromatography and then 200 microg to 70% with
      Reactive red chromatography. The purified Ca(2+)-ATPase displayed the same K(m)
      for calcium and ATP as the native enzyme but a reduced specific activity ranging
      from 4.5 to 7.3 micromol ATP hydrolyzed/min/mg Ca(2+)-ATPase. It was stable and
      active for several days at 4 degrees C or after removal of DM with Bio-beads and
      storage at -80 degrees C.

PMID- 11958777
TI  - Reduced volume of orbitofrontal cortex in major depression.
AB  - BACKGROUND: Functional neuroimaging studies have implicated dysfunction of
      orbitofrontal cortex in the symptoms of depression, and a recent postmortem study
      of depressed patients found reduced density of neurons and glia in this area. The
      purpose of this study was to measure volume of orbitofrontal cortex and other
      frontal cortical subregions in patients with major depression. METHODS: Magnetic
      resonance imaging was used to measure volume of the orbitofrontal cortex and
      other frontal cortical regions in patients with major depression in remission (n
      = 15) and comparison subjects (n = 20). RESULTS: Patients with depression had a
      statistically significant 32% smaller medial orbitofrontal (gyrus rectus)
      cortical volume, without smaller volumes of other frontal regions including
      anterior cingulate Brodmann's area 24 (subgenual gyrus), anterior cingulate
      Brodmann's area 32, subcallosal gyrus (Brodmann's area 25), or whole brain
      volume. The findings were significant after statistically controlling for brain
      size. CONCLUSIONS: These findings are consistent with smaller orbitofrontal
      cortical volume in depression.

PMID- 11958778
TI  - Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes.
AB  - BACKGROUND: Vagus nerve stimulation has shown promising results in an open, acute
      phase pilot study of adults in a treatment-resistant major depressive episode.
      This open, naturalistic follow-up study was conducted to determine whether the
      initial promising effects were sustained, and whether changes in function would
      be observed. METHODS: Thirty adult outpatients in a treatment-resistant,
      nonpsychotic major depressive episode received an additional 9 months of vagus
      nerve stimulation treatment following exit from the 3-month acute study. Changes
      in psychotropic medications and vagus nerve stimulation stimulus parameters were
      allowed during this longer-term follow-up study. A priori definitions were used
      to define response (> or = 50% reduction in baseline Hamilton Rating Scale for
      Depression total score) and remission (Hamilton Rating Scale for Depression < or
      = 10). RESULTS: The response rate was sustained [40% (12/30) to 46% (13/28); p
      =.317] and the remission rate significantly increased [17% (5/30) to 29% (8/28);
      p =.045] with an additional 9 months of long-term vagus nerve stimulation
      treatment after exit from the acute study (1 year total vagus nerve stimulation
      treatment). Significant improvements in function between acute study exit and the
      1-year follow-up assessment as measured by the Medical Outcomes Study Short Form
      36 were observed. CONCLUSIONS: Longer-term vagus nerve stimulation treatment was
      associated with sustained symptomatic benefit and sustained or enhanced
      functional status in this naturalistic follow-up study.

PMID- 11958779
TI  - Early physical and sexual abuse associated with an adverse course of bipolar
      illness.
AB  - BACKGROUND: There is growing awareness of the association between physical and
      sexual abuse and subsequent development of psychopathology, but little is known,
      however, about their relationship to the longitudinal course of bipolar disorder.
      METHODS: We evaluated 631 outpatients with bipolar I or II disorder for general
      demographics, a history of physical or sexual abuse as a child or adolescent,
      course of illness variables, and prior suicide attempts, as well as SCID-derived
      Axis I and patient endorsed Axis II comorbidity. RESULTS: Those who endorsed a
      history of child or adolescent physical or sexual abuse, compared with those who
      did not, had a history of an earlier onset of bipolar illness, an increased
      number of Axis I, II, and III comorbid disorders, including drug and alcohol
      abuse, faster cycling frequencies, a higher rate of suicide attempts, and more
      psychosocial stressors occurring before the first and most recent affective
      episode. The retrospectively reported associations of early abuse with a more
      severe course of illness were validated prospectively. CONCLUSIONS: Greater
      appreciation of the association of early traumatic experiences and an adverse
      course of bipolar illness should lead to preventive and early intervention
      approaches that may lessen the associated risk of a poor outcome.

PMID- 11958780
TI  - Enhanced recognition of disgust in bipolar illness.
AB  - BACKGROUND: Bipolar disorder is associated with functional and structural
      abnormalities in the brain circuits involved in processing emotional stimuli.
      Although impairments of cognitive function have been found to persist in bipolar
      patients during periods of euthymic mood, it is not known whether abnormalities
      in emotional processing also occur during these periods of recovery. METHODS: The
      present investigation assessed the ability of euthymic patients with bipolar
      disorder to recognize different facial expressions of emotion, compared with
      matched controls. A nonemotional facial categorization task was used to control
      for possible nonspecific differences in perception or attention. RESULTS: In
      contrast to the small impairments seen in the nonemotional categorization task,
      patients with bipolar disorder showed a robust facilitation in the discrimination
      of disgusted facial expressions. The recognition of other basic negative and
      positive emotions was unchanged. CONCLUSIONS: The present results suggest a
      selective facilitation of the processes involved in recognizing facial
      expressions of disgust in patients with bipolar disorder. This difference in
      perception may be relevant to the decreased self-esteem and social functioning
      that have been associated with the euthymic phase of this disorder.

PMID- 11958781
TI  - High rate of autoimmune thyroiditis in bipolar disorder: lack of association with
      lithium exposure.
AB  - BACKGROUND: We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs)
      and thyroid failure in outpatients with bipolar disorder compared with two
      control groups. METHODS: The TPO-Abs of outpatients with DSM-IV bipolar disorder
      (n = 226), a population control group (n = 252), and psychiatric inpatients of
      any diagnosis (n = 3190) were measured. Thyroid failure was defined as a raised
      thyroid stimulating hormone level, previously diagnosed hypothyroidism, or both.
      Subjects were compared with attention to age, gender, and exposure to lithium.
      RESULTS: The TPO-Abs were more prevalent in bipolar patients (28%) than
      population and psychiatric controls (3-18%). The presence of TPO-Abs in bipolar
      patients was associated with thyroid failure, but not with age, gender, mood
      state, rapid cycling, or lithium exposure. Thyroid failure was present in 17% of
      bipolar patients and more prevalent in women. It was associated with lithium
      exposure, especially in the presence of TPO-Abs, but not with current rapid
      cycling, although an association may have been masked by thyroid hormone
      replacement. CONCLUSIONS: Thyroid autoimmunity was highly prevalent in this
      sample of outpatients with bipolar disorder and not associated with lithium
      treatment. These variables appear to be independent risk factors for the
      development of hypothyroidism, especially in women with bipolar disorder.

PMID- 11958783
TI  - Serotonergic functioning in children with oppositional defiant disorder: a
      sumatriptan challenge study.
AB  - BACKGROUND: Several studies support the notion that disturbances in the central
      serotonergic function are related to impulsive aggression. There is recent
      evidence from studies on 5-HT(1B) knock-out mice that this specific receptor is
      involved in impulsive aggressive behavior. The aim of the present study was to
      investigate 5-HT(1B/1D) receptor functioning in normal intelligent hospitalized
      children with oppositional defiant disorder (ODD). METHODS: The growth hormone
      (GH) response to a challenge with the 5-HT(1B/1D) agonist sumatriptan was
      examined in 20 children with an ODD, of whom 13 had an attention
      deficit/hyperactivity disorder comorbidity, and 15 normal control subjects (NC).
      Blood samples for growth hormone were collected repeatedly between 8:30 and 12:00
      AM. Sumatriptan was administered at 10 AM. The effect of stress due to this
      procedure was assessed by measuring salivary cortisol. RESULTS: The GH response
      was significantly stronger in the children with ODD. After sumatriptan injection
      NC children showed a significant increase in cortisol; no such pattern was
      present in the ODD group. CONCLUSIONS: The results suggest that the postsynaptic
      5-HT(1B/1D) receptor is functionally more sensitive in children with ODD.

PMID- 11958782
TI  - Psychiatric disorders and behavioral problems in children with velocardiofacial
      syndrome: usefulness as phenotypic indicators of schizophrenia risk.
AB  - BACKGROUND: Velocardiofacial syndrome (VCFS), a genetic deletion condition with
      numerous cognitive sequelae, is associated with a high rate of psychiatric
      disorders in childhood. More recently, VCFS has been identified as a high-risk
      factor for developing adult onset schizophrenia. However, it has never been
      demonstrated that the childhood psychiatric disorders found in children with VCFS
      differ from those found in children with a similar degree of cognitive
      impairment. Identification of a specific behavioral (psychiatric) phenotype in
      childhood VCFS offers the potential for elucidating the symptomatic precursors of
      adult onset schizophrenia. METHODS: Twenty-eight children with VCFS and 29 age-
      and cognitively matched control subjects received a standardized assessment of
      childhood psychiatric disorders and behaviors measured by the Child Behavior
      Checklist (CBCL). Findings from the two groups were compared. RESULTS: The rates
      and types of psychiatric disorder and behavior problems in VCFS and cognitively
      matched control subjects were very high, but showed no significant differences.
      CONCLUSIONS: Psychopathology in children with VCFS may not differ from that found
      in cognitively matched control subjects. Another explanation is that subtle
      phenotypic differences in behavior found in VCFS can not be observed using
      standard symptom inventories. The high rate of psychopathology in children with
      VCFS is not a useful phenotypic indicator of high risk for adult onset
      schizophrenia.

PMID- 11958784
TI  - Salivary cortisol concentrations before and after carbon-dioxide inhalations in
      children.
AB  - BACKGROUND: Considerable research implicates over-activity of the hypothalamic
      pituitary adrenal axis in the pathophysiology of adult mood and anxiety
      disorders. The current study evaluates the association between salivary cortisol
      concentrations and response to carbon-dioxide inhalation in children and
      adolescents with anxiety disorders, mood disorders, or no psychiatric illness.
      The central question was whether response to carbon-dioxide inhalation is
      associated with levels of hypothalamic-pituitary adrenal axis activation. If
      confirmed, this would relate hypothalamic-pituitary adrenal axis activation in
      juveniles, as in adults, and response to a well-studied respiratory procedure.
      METHODS: Serial salivary cortisol samples were examined in 98 subjects (ages 9-17
      years), including 62 subjects with an anxiety and/or mood disorder and 36
      nonpsychiatrically ill comparisons. Samples were obtained upon arrival at the
      laboratory, following a tilt test, then before and immediately after a standard
      5% carbon dioxide inhalation procedure. RESULTS: Salivary cortisol levels pre
      carbon-dioxide inhalation were significantly higher in patients sensitive to the
      anxiogenic effects of carbon dioxide (n = 20) than in patients who did not
      respond to carbon dioxide (n = 42) and in healthy subjects, none of whom were
      sensitive to carbon dioxide (n = 36); cortisol concentrations in the latter two
      groups were indistinguishable. Salivary cortisol did not increase during carbon
      dioxide inhalation, irrespective of diagnostic group or degree of reactivity to
      the procedure. CONCLUSIONS: The current data resemble data from studies of
      laboratory-induced panic among adult patients. In both groups, activation of the
      hypothalamic-pituitary adrenal axis is associated with the response to a
      standardized stressor. Similarly, as in adults, carbon-dioxide inhalation in
      juveniles does not produce a significant change in hypothalamic-pituitary adrenal
      axis activation.

PMID- 11958785
TI  - Frontal lobe dysfunction in pathological gambling patients.
AB  - BACKGROUND: Limited data are available about the validity of the diagnosis of
      pathological gambling (PG) and about the etiology and the efficacy of different
      treatment strategies of this disorder; however, similarities in decision-making
      behavior between PG patients and patients with ventromedial prefrontal cortex
      lesions suggest a possible implication of these areas in the pathophysiology of
      this disorder, as in obsessive-compulsive disorder, in which the decision-making
      impairment is significantly associated with response to serotonin reuptake
      inhibitor treatment. Nevertheless, several studies have shown that decision
      making functioning is also impaired in drug-addicted patients who have shown
      abnormalities in ventromedial prefrontal cortex during functional neuroimaging
      studies. METHODS: We assessed the decision-making function mediated by the
      ventromedial prefrontal cortex in 20 PG patients and 40 healthy control (HC)
      subjects using the Gambling Task, which simulates real-life decision-making,
      testing the ability to balance immediate rewards against long-term negative
      consequence. RESULTS: Significant differences were found in Gambling Task
      performance between HC subjects and PG patients, who showed a specific decision
      making profile across the sequence of the game. The dissimilarity does not appear
      to depend on the basic cognitive function deficit of the PG group. CONCLUSIONS:
      These data seem to suggest the existence of a link between PG and other disorders
      (i.e., obsessive-compulsive disorder and drug addiction) all having diminished
      ability to evaluate future consequences, which may be explained at least in part
      by an abnormal functioning of the orbitofrontal cortex.

PMID- 11958786
TI  - Volumetric reduction in left subgenual prefrontal cortex in early onset
      depression.
AB  - BACKGROUND: Subgenual prefrontal cortex (SGPFC) volume reduction has been
      reported in middle age adults with major depression (MD) or bipolar affective
      disorder. In this study, the authors test the hypothesis that SGPFC reduction is
      present in adolescent onset MD, and examine differences in the magnitude of
      reduction in younger versus older women. METHODS: Subgenual prefrontal cortex
      volume was measured from T1 weighted MR images in (1) 30 young women with early
      onset MD versus eight age-matched controls, and (2) 18 middle aged women with
      recurrent MD versus nine age-matched controls. RESULTS: Left SGPFC volume was
      reduced in adolescent and middle aged females with depression. The magnitude of
      the difference between depressed and control groups (average 19% difference) was
      similar in younger and older women. CONCLUSIONS: Left subgenual cingulate volume
      reductions are present in young women with adolescent onset MD.

PMID- 11958787
TI  - Pregna-D'-pentarane structure influences progesterone receptor affinity for DNA.
AB  - Electrophoretic mobility shift assay was used to determine whether pregna-D'
      pentaranes allow progesterone receptor (PR) from rat uterine cytosol to bind
      hormone response element (HRE)-containing oligonucleotide duplexes and to measure
      the affinity of this interaction. The formation of DNA-protein complexes in low
      salt medium was progesterone-related ligand-, temperature-, and PR-dependent, and
      specific for HRE. The highest affinity of PR to DNA (equilibrium K(a) = 0.420 +/-
      0.185 nM(-1)) was found in the presence of the partial agonist/antagonist RU486,
      while the lowest affinity (K(a) = 0.074 +/- 0.013 nM(-1)) was demonstrated with
      the full agonist 6alpha-methyl-16alpha,17alpha-cyclohexanoprogesterone. With the
      exception of the strong full agonist R5020, there was a tendency toward
      correlation between the induced lower affinity of PR for DNA in the context of
      tyrosine aminotransferase HRE and the full agonistic activity of tested
      compounds.

PMID- 11958788
TI  - A simple, accurate, and sensitive assay method of dehydroepiandrosterone sulfate:
      application for quantitative determination in human breast cyst and duct fluids.
AB  - Radioimmunoassay (RIA) is the most prevalent method for measuring small amounts
      of hormones, peptides, and other compounds in human body fluids. The method,
      however, has several problems, such as cross reactions or non-specific reactions
      of the antibody used. In order to establish an improved method for assaying
      dehydroepiandrosterone sulfate (DHEAS) and cholesterol, which are the largest
      components of human breast cyst and duct fluids, we describe a simple, accurate,
      and sensitive method using high-performance liquid chromatography (HPLC). The
      samples were treated with cholesterol oxidase for quantitation of
      dehydroepiandrosterone (DHEA) and free cholesterol, and the respective oxidized
      substances, 4-androstene-3,17-dione and 4-cholesten-3-one, were extracted with n
      hexane. The extracts were analyzed by straight phase HPLC. Effluents were
      monitored by measuring absorption at 240 nm, where a newly introduced
      chromophoric group, an alpha,beta-unsaturated ketone, showed intense absorption
      (epsilon = 16,000). When the total amount of DHEA (DHEAS plus DHEA) was measured,
      the sample had been solvolyzed by sulfatase beforehand. The amounts of DHEAS were
      quantified by comparing the amounts of DHEA before and after solvolysis. Levels
      of free cholesterol, DHEAS, and DHEA in human breast cyst fluids (n = 30) were
      1.77 +/- 1.12 mmol/dl, 8.27 +/- 10.24 micromol/dl, and 0.02 +/- 0.02 micromol/dl
      (means +/- SD), respectively. The levels of sterol and steroid measured in breast
      duct fluids that were turbid, brown, dark green, or milky in color (n = 9) (mean
      levels, 3.20 +/- 2.97 mmol/dl for free cholesterol and 14.77 +/- 13.75
      micromol/dl for DHEAS) were significantly (P < 0.01) higher than the levels in
      clear or serous breast fluids (n = 21) (mean levels, 0.14 +/- 0.13 mmol/dl for
      free cholesterol and 0.04 +/- 0.07 micromol/dl for DHEAS).

PMID- 11958789
TI  - Acute relaxant effects of 17-beta-estradiol through non-genomic mechanisms in
      rabbit carotid artery.
AB  - Estrogens could play a cardiovascular protective role not only by means of
      systemic effects but also by means of direct effects on vascular structure and
      function. We have studied the acute effects and mechanisms of action of 17-beta
      estradiol on vascular tone of rabbit isolated carotid artery. 17-Beta-estradiol
      (10, 30, and 100 microM) elicited concentration-dependent relaxation of 50 mM KCl
      induced active tone in male and female rabbit carotid artery. The stereoisomer 17
      alpha-estradiol showed lesser relaxant effects in male rabbits. Endothelium
      removal did not modify relaxation induced by 17-beta-estradiol. The NO synthase
      inhibitor L-NAME (100 microM) only reduced significantly relaxation produced by
      30 microM 17-beta-estradiol. Relaxation was not modified by the estrogen receptor
      antagonist ICI 182,780 (1 microM), the protein synthesis inhibitor cycloheximide
      (1 microM), and the selective K(+) channel blockers charybdotoxin (0.1 microM)
      and glibenclamide (1 microM). CaCl(2) (30 microM -10 mM) induced concentration
      dependent contraction in rabbit carotid artery depolarized by 50 mM KCl in Ca(2+)
      free medium. Preincubation with 17-beta-estradiol (3, 10, 30, or 100 microM) or
      the L-type Ca(2+) channel blocker nicardipine (0.01, 0.1, 1, or 10 nM) produced
      concentration-dependent inhibition of CaCl(2)-induced contraction. In conclusion,
      17-beta-estradiol induces endothelium-independent relaxation of rabbit carotid
      artery, which is not mediated by classic estrogen receptor and protein synthesis
      activation. The relaxant effect is due to inhibition of extracellular Ca(2+)
      influx to vascular smooth muscle, but activation of K(+) efflux is not involved.
      Relatively high pharmacological concentrations of estrogen causing relaxation
      preclude acute vasoactive effects of plasma levels in the carotid circulation.

PMID- 11958790
TI  - New pregnane glycosides from Stelmatocrypton khasianum.
AB  - Four new pregnane glycosides, stelmatocryptonoside A, B, C, and D (1-4), were
      isolated from the stems of Stelmatocrypton khasianum. On the basis of chemical
      and spectral data, the structures of 1-4 were established as 3beta, 16alpha
      dihydroxy-pregn-5-en-20-one-16-O-beta-D-glucopyranosyl-(1-->2)-[beta-D
      glucopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside;
      3beta, 20-dihydroxy-pregn-5-en-20-beta-D-glucopyranosyl-(1-->6)-beta-D
      glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-(1-->2)-beta-D-digitalopyranoside;
      3beta, 16alpha-dihydroxy-pregn-5-en-20-one-16-O-beta-D-glucopyranosyl-(1-->2)
      beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside; and 3beta, 16alpha
      dihydroxy-pregn-5-en-20-one-16-O-beta-D-glucopyranosyl-(1-->6)-beta-D
      glucopyranosyl-(1-->6)-beta-D-glucopyranoside. This is the first report of
      pregnane glycosides with sugar chains linked at C-16 of the aglycone.

PMID- 11958791
TI  - Effect of chirality at C-20 of methyl 11beta,17alpha,20-trihydroxy-3-oxo-1,4
      pregnadien-21-oate derivatives on antiinflammatory activity.
AB  - In an effort to determine the C-20 chirality effect on the antiinflammatory
      activity of 17beta-glycolate esters, methyl 11beta,17alpha,20-trihydroxy-3-oxo
      1,4-pregnadien-21-oate and its 9alpha-fluoro analog, their acetonide and their
      carbonate derivatives were synthesized and evaluated. The agents were tested for
      their binding potency to the macrophage glucocorticoid receptor, and their effect
      on LPS-induced nitric oxide generation in RAW 264.7 cells. The acetonide
      derivatives showed the highest binding affinity while the triols and carbonates
      bound rather poorly to the receptors. With the exception of the triols, the alpha
      isomer in each pair of the agents exhibited higher binding affinity to the
      receptor than its corresponding beta-isomer, clearly indicating that C-20
      chirality has a significant effect on antiinflammatory activity. In addition, the
      alpha-isomers of the acetonides showed substantially higher binding affinity than
      the parent compound, prednisolone. In contrast to the high binding activity
      exhibited by some of the acetonides, all of the agents showed weak inhibitory
      effect on NO generation. Metabolic inactivation during assessment of NO
      inhibition may play a role in the divergence noted between receptor affinity and
      the measured biologic activity resulting from the binding.

PMID- 11958792
TI  - Sex steroids in serum of prepubertal male and female horses and correlation with
      bone characteristics.
AB  - We used radioimmunoassay (RIA) to measure monthly serum levels of unconjugated
      and conjugated sex steroids (testosterone T, androstenedione A, estradiol E(2),
      and estrone E(1)) in 4 male and 4 female foals during their first year of life.
      Maximal production of sex steroids was detected from April to August with
      hormonal peaks, corresponding to the natural breeding season in adults. In males,
      only A levels were more steady. Total estrogens (unconjugated plus conjugated
      E(2) and E(1)) were the major steroids in immature males in contrast to adults.
      Estrogens generally peaked in young females before males; the major estrogen was
      E(1), and total estrogens overtook total androgens (unconjugated and conjugated T
      and unconjugated A). We also sampled 3 male and 3 female foals with bone
      alterations in adulthood. For all animals, serum levels of four bone formation
      markers were obtained: osteocalcin (O), hydroxyproline (HP), and alkaline
      phosphatase (AP), and a radiographic score was determined. Only male foals with
      normal skeletal frame (good radiographic score GRS) in adulthood showed a
      correlation (P < 0.01) between the distribution frequency of each bone formation
      marker and unconjugated E(2) or E(1) levels; this finding highlighted the role of
      unconjugated estrogens in bone maturation in horses, since this was not found in
      the groups with bone alterations. In females, the threshold of estrogen synthesis
      and sensitivity was probably sufficient to be a nonlimiting factor at this stage
      of development. Our results strongly suggest a differential regulation of the
      estrogen/androgen balance in horses according to sex, sexual maturation, and
      photoperiod. Moreover, estrogens appear to be crucial for skeletal development in
      male colts, and these steroids are good modulators of skeletal frame
      characteristics in adulthood.

PMID- 11958793
TI  - Synthesis and receptor-binding examination of 16-hydroxymethyl-3,17-estradiol
      stereoisomers.
AB  - The four 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers were
      synthesized and tested in a radioligand-binding assay. The estrogen receptor
      recognizes these compounds, but their relative binding affinities are lower than
      2.0% relative to that of the reference molecule estra-1,3,5(10)-triene-3,17beta
      diol. The affinities of the tested compounds for the androgen and progesterone
      receptors are very low (K(i)> 100 microm and 1 microM, respectively). The
      prepared 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers are therefore
      estrogen receptor-selective molecules.

PMID- 11958794
TI  - The ligand binding profiles of estrogen receptors alpha and beta are species
      dependent.
AB  - Estrogens and selective estrogen receptor modulators are used for the treatment
      and prevention of conditions resulting from menopause. Since estrogens exert
      their activity by binding to nuclear receptors, there is intense interest in
      developing new ligands for the two known estrogen receptor subtypes, ER-alpha and
      ER-beta. Characterization assays used to profile new estrogen receptor ligands
      often utilize receptors from different species, with the assumption that they
      behave identically. To test this belief, we have profiled a number of estrogens,
      other steroids, phytoestrogens and selective estrogen receptor modulators in a
      solid phase radioligand binding assay using recombinant protein for human, rat,
      and mouse ER-alpha and ER-beta. Certain compounds show species dependent binding
      preferences for ER-alpha or ER-beta, leading to differences in receptor subtype
      selectivity. The amino acids identified by crystallography as lining the ligand
      binding cavity are the same among the three species, suggesting that as yet
      unidentified amino acids contribute to the structure of the binding site. We
      conclude from this analysis that the ability of a compound to selectively bind to
      a particular ER subtype can be species dependent.

PMID- 11958795
TI  - Cesium cholate: determination of X-ray crystal structure indicates participation
      of the ring hydroxyl groups in metal binding.
AB  - The crystal structure of cesium cholate, C(24)H(36)(OH)(3) COOCs has been
      determined with three-dimensional X-ray diffractometer data. It crystallized in
      the monoclinic space group P2(1) with unit-cell dimensions a = 11.543(5) A, b =
      8.614(3) A, and c = 12.662(5) A, beta(deg) = 107.95(2), V = 1197.7 A(3) and Z =
      2. The atomic parameters were refined to a final r = 0.0269 and R(omega) = 0.0280
      for 2342 observed reflections. Each Cs(+) is coordinated to 7 oxygen atoms from 5
      different cholate anions with Cs-O distances ranging from 2.957(4) A to 3.678(5)
      A. In this crystal, 5 cholates are coordinated with 1 Cs(+), and 5 Cs(+) are
      coordinated with 1 cholate anion. Carboxyl and all the 3 ring hydroxyl groups of
      cholate anion participate in binding to Cs(+) simultaneously, and there is no
      water molecule coordinated with the Cs(+). The pattern of successive rows
      arranged with polar (p) and non-polar (n) faces in apposition leads to the
      formation of a sandwich sheet structure with polar and non-polar channels. The Cs
      ions lie within the polar interior of the sandwich. The H-bond network is
      reorganized in forming cesium cholate from cholic acid. All the oxygen atoms in
      cholate anion are involved in H-bonding reciprocally or with water molecules to
      form an extensive 3-dimensional network of H-bonds. Compared with cholic acid and
      other similar type of steroids, the coordination structure and H-bonding of Cs
      cholate crystal are distinct.

PMID- 11958796
TI  - Testosterone inhibits bradykinin-induced intracellular calcium kinetics in rat
      aortic endothelial cells in culture.
AB  - Sex steroids have been associated with cardiovascular diseases and the
      modification of the risk of coronary artery disease (CAD). We cultured aortic
      endothelial cells from young adult male rats and loaded them with Fura 2 in order
      to evaluate the direct effects of testosterone on endothelial cells and the
      probable regulation of bradykinin-induced effects on intracellular calcium
      ([Ca(2+)](i)) kinetics, effects that are mediated through an increase in
      intracellular [IP(3)], which in turn stimulates the rapid release of Ca(2+) from
      ER stores. Our results show that testosterone had no direct effects on
      [Ca(2+)](i) kinetics, but did block bradykinin-induced increases in intracellular
      calcium concentration in endothelial cells. This effect was concentration
      dependent; the steroid was applied only 30 s before bradykinin application and
      thus, the effect can be considered nongenomic in origin. Membrane localization of
      a putative androgen receptor in endothelial cells could be responsible for this
      effect. In summary, testosterone can modulate the effects induced by activation
      of membrane-bound bradykinin receptors.

PMID- 11958797
TI  - Two neuroactive steroids in midpregnancy as measured in maternal and fetal sera
      and in amniotic fluid.
AB  - Allopregnanolone and pregnenolone sulfate, which are neuroactive steroids that
      differentially modulate the sensitivity of GABA(A) and NMDA receptors, were
      measured simultaneously in maternal and fetal sera and in amniotic fluid for the
      first time during the second trimester of gravidity. The study included 33
      pregnant women, who underwent cordocentesis due to suspicion of fetal abnormality
      or alloimmunization. Allopregnanolone concentrations in maternal and fetal sera
      were similar and close to the previously found levels in healthy controls at 20
      weeks of gestation The levels of pregnenolone sulfate in maternal serum were 2-3
      times higher and in fetal serum, as much as 10-25 times higher than those found
      by others in the serum of healthy, non-pregnant women. A positive correlation
      between maternal and fetal allopregnanolone indicate similar 5alpha-reductase
      activities or the efficient transport of allopregnanolone between the two
      subjects. No correlation of pregnenolone sulfate levels between mother and fetus
      was found. This finding suggests the autonomous production of pregnenolone
      sulfate in mother and fetus.

PMID- 11958798
TI  - Sterols in erg mutants of Phycomyces: metabolic pathways and physiological
      effects.
AB  - Phycomyces is a fungal producer of beta-carotene and other beneficial
      metabolites. Several erg mutants of Phycomyces, originally selected to study the
      effects of membrane alteration on physiological responses, have now been used to
      gain information about sterol biosynthesis in filamentous fungi. One mutant, H23,
      and its progeny were found to be blocked at episterol C-5 dehydrogenase and did
      not produce ergosterol or any other sterol with a conjugated Delta(5,7) diene
      system. This mutant showed abnormal phototropism, which was correlated with the
      altered sterol composition. Another mutant, H25, seems to be a regulatory mutant.
      All analyzed mutants synthesized ergosta-7,22,24(28)-trien-3beta-ol,
      demonstrating for the first time that the sterol C-22 dehydrogenase of Phycomyces
      is capable of recognizing sterols with a 24(28) unsaturated side chain. New
      evidence regarding the biogenesis of neoergosterol and phycomysterols, the
      potential sparking function of cholesterol, as well as the regulation of sterol
      biosynthesis in this fungus is also reported. Given these results, a pathway for
      sterol biosynthesis in Phycomyces is proposed.

PMID- 11958799
TI  - Prospective evaluation of the quality of oral anticoagulation management in an
      outpatient clinic and in general practices.
AB  - OBJECTIVE: To compare the quality of oral anticoagulant therapy (QOAT), before
      and after referral of patients on oral anticoagulant therapy (OAT) from a
      hospital outpatient clinic (HOC) to general practitioners (GPs). DESIGN:
      Prospective observational study. Patients were identified by using the Laboratory
      Information System (LIS), containing all prescribed International Normalised
      Ratio of Prothrombin Time (INR) tests, from the HOC and GPs in the hospital
      submission area. SETTING: The HOC in a rural hospital, Aarhus County, Denmark
      (55,000 inhabitants), and GPs in the submission area. SUBJECTS: 124 OAT patients
      (59.7% males. Median age 70.0: 25-75 percentile: 62.0-76.0). MAIN OUTCOME
      MEASURE: The QOAT in terms of time spent within therapeutic INR interval (TI).
      The QOAT was compared 8 months before with 8 months after altering the monitoring
      organization. For patients monitored less than 8 months before the alteration,
      the QOAT was compared to a corresponding time period after the alteration.
      RESULTS: We identified 124 OAT patients, and found a significant increase in the
      QOAT from 65.0% before to 69.1% after referral of the patients to the GPs
      (P<.0001). In 75 patients with full follow-up, the QOAT increased from 67.5%
      before to 69.7% after the alteration (P<.0001). CONCLUSION: The results indicate
      that the QOAT in this geographical area is adequate, and that the quality
      performed by the GPs was at least as good as in the HOC. In order to document and
      increase the QOAT, continuous quality surveillance using the LIS has been
      initiated.

PMID- 11958800
TI  - Premature arterial and venous events in three families. Effect of folate levels
      and MTHFR mutation mediated by family/generation and homocysteine levels.
AB  - Plasma homocysteine levels result from the effect of genetic and environmental
      factors. We investigated the hypothesis of familial association between folates,
      methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia with acute
      events, studying three families through pedigree analysis and log-linear
      graphical models. In 43 subjects, 13 had homocysteine levels of >15 micromol/l.
      In Family A, premature venous and arterial events occurred in father and son,
      respectively. In Family B, several arterial premature events occurred and very
      high homocysteine level was found in a healthy 18-year-old nephew. In Family C,
      stroke occurred at the age of 16 in a boy. In all three families, all subjects
      with premature cardiovascular events had high homocysteine level as well as MTHFR
      mutation, either homozygous or heterozygous. The present results underline that
      hyperhomocysteinemia has a direct conditional association with cardiovascular
      events. Moreover, homocysteine level is a variable that links the indirect
      association of folates, MTHFR mutation and cardiovascular event.

PMID- 11958801
TI  - Prevalence, isotype, and functionality of antiheparin-platelet factor 4
      antibodies in patients treated with heparin and clinically suspected for heparin
      induced thrombocytopenia. The pathogenic role of IgG.
AB  - Antibodies to heparin-platelet factor 4 (PF4) complexes have been observed in
      patient with heparin-induced thrombocytopenia (HIT) syndrome. These antibodies
      may be of various isotypes and differ with respect to their ability to activate
      platelets/endothelial cells. This study determined the isotypes and functionality
      of antiheparin-platelet factor 4 (AHPF4) antibodies in 111 patients treated with
      heparin and clinically suspected for HIT. In this patient population, 50% had
      detectable AHPF4 cumulative IgA, IgG, and IgM (determined by enzyme-linked
      immunosorbent assay, ELISA), but only 35% was positive when tested with the (14)C
      serotonin release assay (SRA). Using antihuman Ig specific for different
      isotypes, we found that 50% of the 111 samples was positive for IgG, 45% for IgM,
      and 37% for IgA. In 50 normal human serum (NHS) samples, only two were positive
      for IgG, but 33 were positive for IgM, indicating a potential humoral response to
      the heparin-PF4 complex prior to heparin administration. Patients that were
      ELISA(+) for AHPF4 antibody titer were subdivided into SRA-positive (+) and SRA
      negative (-) groups. The SRA(+) group had a mean ELISA optical density (OD) for
      AHPF4 IgA/IgG/IgM of 2.1, while the SRA(-) group had a mean OD of 0.8 (P<.001).
      The SRA(+) group had greater mean OD values for all three individual isotypes.
      Using flow cytometry, we determined the ability of different patient samples to
      activate platelets. Samples that contained IgG and were SRA(+) activated
      platelets (as measured by microparticle generation and P-selectin expression) in
      the presence of therapeutic concentrations of heparin. NHS and samples containing
      IgA and/or IgM that were SRA(-) were not able to produce microparticles nor were
      they able to increase expression of P-selectin. Together, these data indicate
      that IgG is the principal mediator of platelet activation in patients with HIT,
      with IgA and IgM playing a less significant role in the pathophysiology of this
      syndrome.

PMID- 11958802
TI  - Pathological haemostasis and "prothrombotic state" in Behcet's disease.
AB  - Behcet's disease (BD) is a widespread occlusive-type vasculitis with life
      threatening manifestations. The vasculopathy of BD is unique and any type of
      vessel can be involved. Moreover, vascular lesions in BD represent an occlusive
      nature suggesting a hypercoagulable/prothrombotic state. The data concerning the
      genetic defects of the coagulation cascade are expanding. There is evidence of
      universal activation of haemostatic system in BD. Procoagulant markers of
      thrombosis are elevated reflecting intravenous excessive thrombin formation.
      Defective fibrinolysis with impaired fibrinolytic kinetics may have a role in the
      hypercoagulable/prothrombotic state of BD. Endothelial cell injury and/or
      pathological activation is well documented in BD. The aim of this paper is to
      review current literature knowledge and our experience regarding the unresolved
      complicated issues of genetic thrombotic defects, in vivo haemostatic markers,
      coagulation inhibitors, impaired fibrinolysis, and endothelial injury/dysfunction
      of the hypercoagulable/prothrombotic state of BD. The clinical aspects of
      vascular thrombosis, the genetic basis of coagulation, coagulation inhibitors,
      fibrinolysis inhibitors, and endothelial dysfunction are reviewed. Challenges and
      future prospects regarding the prothrombotic state of BD are discussed together
      with new promising antithrombotic and antiplatelet treatment strategies. Better
      understanding of the exact pathogenesis of the hypercoagulable/prothrombotic
      state of this disease may help to develop novel therapeutic approaches offering a
      better outcome for Behcet's patients with thrombosis.

PMID- 11958803
TI  - A novel family with recessive von Willebrand disease due to compound
      heterozygosity for a splice site mutation and a missense mutation in the von
      Willebrand factor gene.
AB  - We report a new family with autosomal recessive von Willebrand disease (VWD) in
      which the propositus was compound heterozygous for a missense mutation in exon 42
      (G7085T, C2362F) and a C-->A splice site mutation in intron 13 of the von
      Willebrand factor (VWF) gene. The propositus had factor VIII:C approximately
      equal to 20 IU/dl, VWF antigen 5-7 IU/dl and ristocetin cofactor activity <3-7
      IU/dl. The bleeding time (BT) was markedly prolonged (>15 min). Haplotype
      analysis and mutation screening were conducted by polymerase chain reaction (PCR)
      based methodology. Each mutation appeared to be linked to a haplotype that was
      identical to the haplotype previously detected in subjects in the Veneto region
      carrying these mutations, suggesting a founder effect. In the propositus' family
      six subjects were heterozygotes for the C2362F mutation and five were
      heterozygotes for the splice site mutation. None of the heterozygotes had
      suffered from significant bleeding. The mutation C2362F and the splice site
      mutation in intron 13 are commonly observed in subjects with recessive von
      Willebrand disease in the Veneto region. These mutations are truly recessive and
      cause bleeding only in the compound heterozygous or homozygous state.

PMID- 11958804
TI  - Assessment of omega-fatty-acid-supplemented human platelets for potential
      improvement in long-term storage.
AB  - Uptake of omega (omega)-3 fatty acids can influence membrane stability and cell
      mobility. We investigated the effects of omega-3 and -6 fatty acids on the
      hemostatic efficacy of human platelets using an in vivo rabbit bleeding model. In
      vitro assays such as platelet aggregation, vWF bead-mediated ATP release and
      platelet adhesion to beads (measured by the residual platelet count [RPC] [free
      platelet count after reacting with the beads]/[baseline platelet count]x
      100=%RPC; a high %RPC indicates reduced platelet function) were conducted on
      platelets treated with 1% fish oil (omega-3); 2% fish oil emulsion or 1% soy oil
      (omega-6). Oil treatment of platelets reduced the vWF bead-induced ATP release
      insignificantly. Addition of omega-3 agents reduced physical reactivity (%RPC)
      with the vWF beads by a factor of 1.2 (oil) and 1.9 (emulsion). The omega-6 oil
      enhanced reactivity by a factor of 1.7. After washing to remove excess reagent,
      platelet resuspension was most efficient with the omega-3 emulsion. Platelet
      function was higher with the omega-3-treated platelets (%RPC=52.3%, omega-3 oil;
      63.3%, omega-3 emulsion vs. 85%, omega-6 oil; 82% untreated platelets). Ethyl
      palmitate-treated thrombocytopenic rabbits were infused with human platelets.
      Survival times of the treated platelets, as monitored by flow cytometry (6.2-8.2
      h) were comparable to untreated platelets (8.6 h). In the rabbit kidney injury
      model, blood loss after infusion of the treated platelets was similar to that of
      saline-infused rabbits (75.3+/-3.4 g). However, platelets washed prior to
      infusion reduced blood loss to a value comparable to that of fresh platelets
      (48.3+/-5 g). Furthermore, the presence of the infused platelets at the injury
      site was clearly visualized using FITC-tagged anti CD42a antibody. Thus, the
      omega-3-based agents protect the platelets from damage during the washing
      procedure as demonstrated in vitro by improved platelet resuspension, low %RPC,
      high stimulus-responsive ATP secretion and a reduction in blood loss in vivo.

PMID- 11958805
TI  - Effects of alcohol ingestion post-exercise on platelet aggregation.
AB  - The present study examined the influence of ingesting a moderate dose of alcohol
      on platelet count and platelet aggregation during recovery following exercise.
      Nineteen subjects (11 male and 8 female) were studied immediately after a
      standardised cycle ergometer test and during the 24-h period of recovery. In
      random order, alcohol (0.7 g/kg body mass) was given 1 h after exercise on one
      test occasion, while an equal volume of alcohol-free solution was administered on
      the other. Venous blood samples were obtained at baseline, post-exercise, and at
      1, 5, and 22 h post-alcohol ingestion. Blood alcohol level increased
      significantly 1 h after the ingestion of alcohol, but decreased and returned to
      the resting baseline level at 5 h during recovery. Males and females subjects
      exhibited similar mean values of platelet count, platelet aggregation, and beta
      thromboglobulin concentration at rest and following exercise and recovery. A
      significant increase in platelet count and a decrease in platelet aggregation
      using adenosine diphosphate (ADP) was found following exercise. Although plasma
      beta-thromboglobulin level (pooled data for males and females) showed an increase
      by 26.0% (from a mean pre-exercise value of 22.3-28.1 IU/ml), this rise was not
      significant (P>.05). The post-exercise increase in platelet count was mainly due
      to exercise-induced plasma volume loss. During recovery, while the increase in
      platelet count post-exercise returned to the baseline level in control and
      alcohol trials, the optical density of platelet aggregation remained
      significantly depressed at 5-h during recovery in the alcohol trial but not in
      the normal control condition. It is concluded that exercise induces significant
      reduction in platelet aggregation and the consumption of alcohol after physical
      exercise delays the normal return of platelet aggregation to the resting baseline
      levels during recovery.

PMID- 11958806
TI  - Trimucytin, a collagen-like snake venom protein, activates platelets independent
      of I-domain within alpha2 subunit of alpha2beta1 integrin.
AB  - Trimucytin is a powerful platelet aggregation inducer isolated from the venom of
      Taiwan habu snake (Trimeresurus mucrosquamatus). In this study, we found that the
      snake venom protein, crovidisin, which prevents collagen-platelet interaction
      through its high-affinity binding to collagen, inhibited competitively trimucytin
      induced aggregation of washed human platelets with a pA(2) value of 6.65. The
      ability of trimucytin in triggering platelet aggregation was suppressed by a
      monoclonal antibody (A2-IIE10) raised against the alpha2 subunit of alpha2beta1
      integrin (glycoprotein Ia/IIa), indicating that platelet alpha2beta1 integrin
      plays a central role in trimucytin's platelet reactivity. Many studies have
      localized the major reactive site of alpha2beta1 integrin to the I-domain of
      alpha2 subunit. However, Escherichia coli-produced recombinant alpha2 I-domain
      (GST-alpha2 fusion protein) blocking collagen-induced platelet aggregation failed
      to inhibit aggregation of platelets in response to trimucytin. Based on these
      findings, it is concluded that the platelet reactivity of trimucytin is
      alpha2beta1 integrin-dependent, while the I-domain present in the alpha2 subunit
      is not involved. This novel snake venom protein would be useful for mapping the
      functional domain of alpha2beta1 integrin.

PMID- 11958808
TI  - The role of platelets in blood coagulation--effects of platelet agonists and
      GPIIb/IIIa inhibitors studied by free oscillation rheometry.
AB  - We have studied the contribution of platelets to the coagulation of plasma and
      the effects of activation or inhibition of platelets on the coagulation process
      in unanticoagulated fresh whole blood (subsequently termed native blood). For
      this purpose, we have used a free oscillation rheometer (FOR), the ReoRox4, a new
      instrument that enables noninvasive viscoelastic measurements of clot formation
      in plasma and whole blood. Platelets appear essential for the initiation of
      coagulation if no activating surface is present. We prepared platelet-free plasma
      by quick centrifugation and filtration of native blood, which did not coagulate
      if stored in plastic containers at 37 degrees C but clotted if transferred to
      glass containers. Addition of platelet agonists, such as collagen or the thrombin
      receptor agonist peptide, SFLLRN, significantly accelerated the clotting of
      native blood and also changed the rheometer curve appearance, accelerating both
      onset and completion of clot formation (i.e. fibrin gel formation). Inhibition of
      platelet glycoprotein (GP) IIb/IIIa with the peptide-derived compound MK-852 or
      the antibody-derived abciximab (Reopro) prevented clot retraction and prolonged
      the clotting time with SFLLRN. In collagen-stimulated samples, MK-852 accelerated
      clotting but delayed completion of clotting while abciximab prolonged both
      clotting time and completion of clotting. To our knowledge, this is the first
      report showing that activation of platelets in native whole blood shortens the
      coagulation time ex vivo. It also describes a new instrument that enables studies
      of the viscoelastic properties of a forming whole blood clot.

PMID- 11958807
TI  - Erythropoietin and granulocyte colony-stimulating factor increase plasminogen
      activator inhibitor-1 release in HUVEC culture.
AB  - Recombinant human erythropoietin (rHuEPO) is considered to be a mitogenic and
      chemotactic agent in cultured endothelial cells (ECs). The effect of recombinant
      granulocyte-macrophage (rGM-CSF) and granulocyte (rG-CSF) colony-stimulating
      factors on the proliferation of human umbilical vein endothelial cells (HUVECs)
      has been controversial. METHODS: HUVEC proliferation and the release of
      endothelial markers in HUVEC culture stimulated by rHuEPO, rGM-CSF and G-CSF were
      measured. RESULTS: We found the dose-dependent stimulating effect of rHuEPO and
      rGM-CSF on HUVEC proliferation, but we did not achieve this with rG-CSF. rHuEPO
      like rG-CSF was an effective agent in stimulating the plasminogen activator
      inhibitor (PAI)-1 release from HUVECs to a cultured medium, while rGM-CSF failed.
      CONCLUSION: We suggest that rHuEPO showed prothrombotic changes in HUVEC culture.
      Our results support the idea of suspected rHuEPO direct prothrombotic role in
      haemodialysed patients treated with rHuEPO.

PMID- 11958809
TI  - Clopidogrel inhibits platelet adhesion and platelet-dependent mitogenesis in
      vascular smooth muscle cells.

PMID- 11958810
TI  - Dilute prothrombin time-based lupus ratio test. Integrated LA testing with
      recombinant tissue thromboplastin.
AB  - The lupus ratio (LR) test is a normalized ratio of the clotting times obtained
      with low and high phospholipid (PL) concentrations, where the test plasma is
      mixed 1:1 with normal pooled plasma (NP). As an integrated, automated, and
      computer-assisted assay, this principle has been applied to the dilute activated
      partial thromboplastin time (dAPTT) and dilute Russell viper venom time (dRVVT)
      test systems. In this study, we used recombinant thromboplastin to develop an
      automated LR test based on the dilute prothrombin time (dPT). Using plasma
      samples from a selected group of patients (N=92) with a well-defined lupus
      anticoagulant (LA) status, the dPT-based LR test showed fair agreement with the
      dAPTT-based LR test (kappa=.60, P<.001) and good agreement with the dRVVT-based
      LR test (kappa=.78, P<.001) regarding the classification of plasmas as LA
      negative or -positive. Most discordant plasmas were low positive. Correlation
      between dPT- and dRVVT-positive LRs was only moderate (r(s)=.51, P=.002), and
      correlation between dPT- and dAPTT-positive LRs was nonsignificant (r(s)=.23,
      P=.18). Using dilutions of pooled LA-positive plasma, the dAPTT-based LR test
      appeared to be the most sensitive of the three tests. This study confirms the
      general validity of the LR principle and shows that the dPT-based LR test yields
      reproducible results. The low coefficients of variation (CV) of the LR assays,
      combined with a fairly low correlation among the three tests, support the
      assumption of antibody heterogeneity of LA-positive plasmas and the desirability
      of performing more than one test.

PMID- 11958811
TI  - Anticoagulant effect and action mechanism of sulphated flavonoids from Flaveria
      bidentis.
AB  - Quercetin 3-acetyl-7,3',4'-trisulphate (ATS) and quercetin 3,7,3',4'
      tetrasulphate (QTS) obtained from Flaveria bidentis (Asteraceae) were
      investigated in vitro for anticoagulant activity. Three different concentrations
      of each flavonoid were assayed at different incubation times, showing at 1 mM
      significant prolongation on the activated partial thromboplastin time (APTT),
      less on the prothrombin time (PT), and no effect on the thrombin time (TT). In
      order to define the action mechanism of the anticoagulant activity, all
      coagulation factors were evaluated and no important activity decrease was
      observed, indicating that another mechanism is involved. Thus, thrombin
      inhibition mediated by antithrombin III (ATIII) and heparin cofactor II (HCII)
      activation was investigated in comparison to the physiological activators,
      heparin and dermatan sulphate (DS), respectively. As a conclusion, no activation
      on ATIII for neither flavonoids was observed. On the contrary, QTS much more than
      ATS produced an activation on HCII comparable to the one of DS, indicating that
      these flavonoids act as agonists of this inhibitor. A plausible explanation of
      the effects of both flavonoids could be due to the different degree of sulphation
      of these molecules. According to the results obtained, and taking in account the
      high solubility of these natural products in aqueous media and the nontoxic
      nature of this family of compounds, further investigation on the antithrombotic
      effects of these flavonoids are merited.

PMID- 11958812
TI  - Why is venous thrombosis only rarely detected in patients with suspected
      paradoxical embolism?

PMID- 11958813
TI  - The mechanism of action of antioxidants against lipoprotein peroxidation,
      evaluation based on kinetic experiments.
AB  - Peroxidation of blood lipoproteins is regarded as a key event in the development
      of atherosclerosis. Hence, attenuation of the oxidative modification of
      lipoproteins by natural and synthetic antioxidants in vivo is considered a
      possible way of prevention of cardiovascular disorders. The assessment of the
      susceptibility of lipoproteins to oxidation is commonly based on in vitro
      oxidation experiments. Monitoring of oxidation provides the kinetic profile
      characteristic for the given lipoprotein preparation. The kinetic profile of
      peroxidation is characterized by three major parameters: the lag preceding rapid
      oxidation, the maximal rate of oxidation (V(max)) and the maximal accumulation of
      oxidation products (OD(max)). Addition of antioxidants alters this pattern,
      affecting the kinetic parameters of oxidation. In particular, antioxidants may
      prolong the lag and/or decrease the V(max) and/or decrease the OD(max). Such
      specific variation of the set of kinetic parameters may provide important
      information on the mechanism of the inhibitory action of a given antioxidant
      (scavenging free radicals, metal-binding or other mechanisms). Numerous natural
      and synthetic compounds were reported to inhibit oxidation of lipoproteins. Based
      on the analysis of reported effects and theoretical considerations, we propose a
      simple protocol that relates the kinetic effects of a given antioxidant to the
      mechanism of its action.

PMID- 11958814
TI  - Natural halogenated fatty acids: their analogues and derivatives.
AB  - A comprehensive survey has been made of all fatty acids containing halogen atoms
      covalently bonded to carbon and which are deemed as naturally occurring.
      Generally thought to be minor components produced by many different organisms,
      these interesting compounds now number more than 300. Recent research, especially
      in the marine area, indicates this number will increase in the future. Sources of
      halogenated fatty acids include microorganisms, algae, marine invertebrates, and
      higher plants and some animals. Their possible biological significance has also
      been discussed

PMID- 11958816
TI  - VIth International Congress of Neuroimmunology. Edinburgh, Scotland, September 3
      7, 2001.

PMID- 11958817
TI  - Interleukin-6 and the development of social disruption-induced glucocorticoid
      resistance.
AB  - Following social disruption (SDR) stress in male mice, corticosterone resistance
      of splenocytes was accompanied by enhanced LPS-stimulated interleukin (IL)-6
      secretion. The present study examined the role of IL-6 in the development of
      corticosterone resistance. Addition of IL-6 to control splenocyte cultures did
      not induce corticosterone resistance. SDR also elevated IL-6 in plasma and liver,
      but not in spleen. IL-6 deficient mice that were exposed to SDR developed
      glucocorticoid resistance despite the absence of systemic IL-6. These findings
      suggest that although SDR enhanced IL-6 responses, IL-6 was not essential for the
      development of stress-induced splenocyte corticosterone resistance.

PMID- 11958818
TI  - Expression of functional chemokine receptors by rat cerebellar neurons.
AB  - In this study, we examined chemokine receptor expression and function in rat
      cerebellar neurons. Calcium imaging experiments demonstrated that a wide variety
      of chemokines elicited [Ca(2+)](i) transients in acutely isolated and cultured
      cerebellar Purkinje and granule neurons. In many cases, these chemokine responses
      were pertussis toxin (PTX) insensitive. In addition, chemokines activated the
      Ca(2+) and cAMP-dependent transcription factor CREB and the extracellular
      response kinases ERK1/ERK2. Chemokines increased the survival of Purkinje neurons
      deprived of their trophic support. Thus, the presence of chemokine receptors and
      the signaling pathways they activate suggest that chemokines play a role in the
      control of cerebellar neuron survival and development and may mediate
      communication between the CNS and the immune system.

PMID- 11958819
TI  - Interleukin-1 beta and interferon-gamma induce proliferation and apoptosis in
      cultured Schwann cells.
AB  - This study reports that in Schwann cell tissue culture the administration of the
      two pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interferon
      gamma (IFN-gamma), at different dosages, singly or in combination, can induce
      apoptosis and/or mitosis. Schwann cell apoptosis was maximal within 24 h of
      stimulation with 50 U/ml of IFN-gamma, while proliferation was at its peak within
      24 h with 10 U/ml IL-1 beta, and both processes decreased progressively by 48 and
      72 h. Moreover, the combination of the two cytokines did not show any synergistic
      effect. These data can be interpreted as a possible involvement of pro
      inflammatory cytokines not only in myelin disruption but also in promoting
      remyelination.

PMID- 11958820
TI  - Microglia-derived IGF-2 prevents TNFalpha induced death of mature
      oligodendrocytes in vitro.
AB  - Insulin-like growth factor-2 (IGF-2) present in media conditioned by non
      activated and interferon gamma (IFN gamma)-treated microglia reduces
      galactocerebroside(+) (GalC) oligodendrocyte apoptosis in cultures derived both
      from the CG4 cell line and primary rat cortices. Microglia-derived IGF-2 also
      acts in each culture system to block GalC(+) oligodendrocyte toxicity resulting
      from soluble microglial-derived tumour necrosis factor alpha (TNF alpha). IGF-2
      inhibits TNF alpha-induced c-Jun kinase (JNK) activation of the CG4 cell line.
      Microglial activation results in the release of soluble factors that are
      potentially toxic to oligodendrocytes but this may be offset by the production of
      soluble factors that protect these vulnerable cells. Allowing for extrapolation
      of these in vitro findings to intact tissue, our observations suggest one
      mechanism for limiting bystander damage in the context of inflammatory brain
      disease.

PMID- 11958821
TI  - Peripheral LPS administrations up-regulate Fas and FasL on brain microglial
      cells: a brain protective or pathogenic event?
AB  - We evaluated the effect of single or repeated intraperitoneal daily LPS
      injections on expression of Fas/FasL system within the brain. Results obtained,
      utilizing real-time quantitative RT-PCR, show that, while a bolus injection of
      LPS robustly increases hippocampal Fas, but not FasL, mRNA expression, repeated
      LPS administrations also induce FasL up-regulation. Immunofluorescence studies
      demonstrated, in turn, an increased number of Fas and FasL immunoreactive
      microglial cells within the brain parenchyma. The increase in FasL
      immunoreactivity was, in contrast to Fas, still evident 2 weeks following LPS
      wash-out. At all times, no Fas-positive immunoreactive neurons nor TUNEL-positive
      resident brain cells were observed. Collectively, these data provide further
      support for the existence of innate immune responses in brain and, in addition,
      raise the possibility that Fas and FasL are, within the brain parenchyma,
      differentially regulated.

PMID- 11958822
TI  - Social disruption-induced glucocorticoid resistance: kinetics and site
      specificity.
AB  - Social disruption (SDR) of male mice has been shown to induce a state of
      functional glucocorticoid (GC) resistance in splenocytes. The present study
      demonstrated that GC resistance developed following repeated, but not acute
      exposure to SDR. GC resistance was long-lasting and persisted for at least 10
      days after stress. In contrast, SDR did not alter cytokine secretion from
      peritoneal mononuclear cells treated with corticosterone. These findings suggest
      that SDR-induced GC resistance may be restricted to specific sites such as the
      spleen.

PMID- 11958823
TI  - Brain-derived neurotrophic factor in experimental autoimmune neuritis.
AB  - Long-term disability in Guillain-Barre syndrome (GBS) is associated with axonal,
      and some neuronal, degeneration. Brain-derived neurotrophic factor (BDNF) can
      prevent neuronal death following damage to motor axons and we have therefore
      examined the ability of BDNF to ameliorate the effects of experimental autoimmune
      neuritis (EAN), a model of GBS. Treatment of Lewis rats with BDNF (10 mg/kg/day)
      did not significantly affect the neurological deficit, nor significantly improve
      survival, motor function or motor innervation. The weight of the urinary bladder
      was significantly increased in control animals with EAN, but remained similar to
      normal in animals treated with BDNF. With the exception of a possibly protective
      effect indicated by bladder weight, this study suggests that BDNF may not provide
      an effective therapy for GBS, at least in the acute phase of the disease.

PMID- 11958825
TI  - Occurrence of T cells in the brain of Alzheimer's disease and other neurological
      diseases.
AB  - We investigated the occurrence of T cells in the brain parenchyma of Alzheimer's
      disease (AD), non-AD degenerative dementias and controls by semi-quantitative
      analysis of immunohistochemically stained tissue sections. In all cases, we found
      at least some T cells. The number of T cells was increased in the majority of AD
      cases compared with other cases. The phenotype of T cells in the AD brain
      indicates that they are activated but are not fully differentiated. Antigen
      triggered clonal expansion is not likely to take place. Local inflammatory
      conditions might cause accumulation and activation of T cells in the AD brain.

PMID- 11958824
TI  - Interferon-gamma-induced calcium influx in T lymphocytes of multiple sclerosis
      and rheumatoid arthritis patients: a complementary mechanism for T cell
      activation?
AB  - Autoreactive T lymphocytes are considered to play a crucial role in orchestrating
      a chronic inflammation in the central nervous system (CNS) of multiple sclerosis
      (MS) patients and in the joints of rheumatoid arthritis (RA) patients. However,
      it has been suggested that the majority of T cells in the immune infiltrate are
      nonspecifically recruited into the CNS and into the inflamed joint. In addition,
      several lines of evidence suggest an important role for interferon-gamma (IFN
      gamma) in the pathogenesis of MS and RA. We have studied whether peripheral blood
      T cells from patients with autoimmune diseases are more susceptible to activation
      in the presence of IFN-gamma. The results indicate that IFN-gamma mediates a
      sustained elevated [Ca(2+)](i) in T cells of (active) MS and RA patients as
      compared to healthy controls and patients with common viral infections. No
      [Ca(2+)](i) increase was observed in Ca(2+)-free medium, excluding an effect of
      IFN-gamma on Ca(2+)-release from intracellular stores. Although the IFN-gamma
      activated Ca(2+)-influx is insufficient to induce T cell proliferation in vitro,
      our data indicate a significantly augmented proliferation in response to
      suboptimal doses of PHA in the presence of IFN-gamma. This study suggests that
      the IFN-gamma-induced Ca(2+)-influx can act as a complementary mechanism in the
      activation of blood T lymphocytes from MS and RA patients.

PMID- 11958826
TI  - Catecholamine levels in peripheral blood lymphocytes from multiple sclerosis
      patients.
AB  - Circumstantial evidence suggests the involvement of sympathoadrenergic mechanisms
      in the progress of multiple sclerosis (MS). We studied peripheral blood
      lymphocytes from MS patients. The levels of dopamine (DA), norepinephrine (NE),
      epinephrine (E) and their metabolites in extracts of lymphocytes from 58 MS
      patients and 19 healthy controls were measured by using capillary
      electrophoresis. The MS patients were divided into clinical subgroups: a
      laboratory-supported definitive (first-attack) MS group, and a relapsing
      remitting (RR) group in remission. The peripheral blood lymphocyte level of
      epinephrine was significantly higher in the first-attack MS patients (p=0.028)
      than in the controls. However, the norepinephrine levels were significantly
      (p=0.027) lower in the RR patients in remission. The catecholamines are known to
      be able to affect the lymphocyte activity, both by stimulation and by
      immunosuppression. Our results suggest that the catecholamines are important
      regulators of lymphocyte activation in MS, and of potential importance as
      concerns new diagnostic and therapeutic methods.

PMID- 11958827
TI  - Association between the phenylethanolamine N-methyltransferase gene and multiple
      sclerosis.
AB  - Phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the
      catecholamine biosynthesis pathway, catalyzes the conversion of norepinephrine
      (NE) to epinephrine (EPI). PNMT is a candidate gene for multiple sclerosis (MS)
      for two reasons. PNMT is known to map to a region identified in two genome
      screens for MS and it directly regulates the amounts of NE and EPI, both of which
      play a significant role in the modulation of the innate immune response. The
      frequencies of two promoter polymorphisms of the PNMT gene showed genetic
      association in a case-control study of 108 patients with MS and 774 ethnically
      and age-matched control subjects. In subjects with MS, significant differences in
      the frequency of the GG genotype at the G-387A marker and the AA genotype at the
      G-182A marker were observed. Additionally, when both markers were combined and
      evaluated, highly significant differences between the polymorphism distributions
      in patients with MS and control subjects were detected. The data suggest that
      these promoter polymorphisms of the PNMT gene, both independently and
      cumulatively, show association with MS.

PMID- 11958828
TI  - Regulatory effects of estriol on T cell migration and cytokine profile:
      inhibition of transcription factor NF-kappa B.
AB  - The protective role of pregnancy in autoimmune conditions, such as multiple
      sclerosis (MS), is potentially associated with immune regulation by sex hormones
      produced during pregnancy. This study was undertaken to examine the regulatory
      effects of estriol on the T cell functions, including transmigration and the
      cytokine production. The results revealed for the first time that estriol
      significantly inhibited T cell transmigration at a concentration range typical of
      pregnancy, which correlated with decreased T cell expression of matrix
      metalloproteinase-9. Estriol was also found to alter the cytokine profile of T
      cells toward Th2 phenotype by up-regulating the production of IL-10 and
      inhibiting TNFalpha secretion of T cells. However, the inhibitory effects of
      estriol on T cells were not antigen-dependent. Further characterization indicated
      that estriol inhibited nuclear transcription factor kappa B (NF-kappa B), which
      controls a variety of immune-related genes. This study provides new evidence that
      estriol is a potent regulator for the T cell functions potentially through its
      interaction with the NF-kappa B signaling pathway.

PMID- 11958829
TI  - 5-HT(1A) receptor antagonist p-MPPI attenuates acute ethanol effects in mice and
      rats.
AB  - The effect of a selective 5-HT(1A) antagonist, 4-(2'-methoxy-)phenyl-1-[2'-(N-2"
      pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI), on acute ethanol-induced
      hypothermia, sleep and suppression of acoustic startle reflex in C3H/He mice and
      Wistar rats was studied. Administration of p-MPPI at the doses of 0.4, 0.7 and
      1.0 mg/kg reduced in a dose-dependent manner the ethanol-induced hypothermia and
      the sleep time and attenuated the ethanol-induced decrease of acoustic startle
      reflex magnitude in mice. Similar p-MPPI (0.4 mg/kg) effects on ethanol-induced
      sleep and hypothermia were obtained in rats. It was concluded that 5-HT(1A)
      receptors were involved in the mechanisms of the ethanol-induced hypothermia and
      sleep, and that 5-HT(1A) antagonist increased acute ethanol tolerance.

PMID- 11958830
TI  - Cortical brain responses to semantic incongruity and syntactic violation in
      Italian language: an event-related potential study.
AB  - The present experiment investigated cortical responses of native Italian subjects
      during reading of short sentences including semantic or morphosyntactic
      violations. Given the specificity of the Italian language in which the sequencing
      of words is relatively more free than in English or other languages, we
      investigated whether syntactic and semantic violations were able to elicit event
      related potential (ERP) components similar to those found in other languages.
      Cortical potentials evoked by the anomalous target word were recorded at frontal,
      central and parietal electrodes. Results showed that, in Italian, semantic
      anomaly elicited a negative wave (N400) in the 400-500 ms time-window and
      syntactic error evoked a slower positive wave (P600) in the 500-700 ms time
      window. Syntactic error also evoked a significant left anterior negativity in the
      350-450 ms time-window, supporting the view that syntactic processes precedes
      semantic analysis. Thus, Italian language, notwithstanding its specificity, shows
      ERPs responses to semantic and syntactic violations, with effects, scalp
      distribution and latency similar to those found in German, Dutch and English.
      Results point to a cross-linguistic consistency of the semantic and syntactic ERP
      components associated with the detection of linguistic anomalies.

PMID- 11958831
TI  - Sequence conservation between mouse and human synphilin-1.
AB  - Synphilin-1 has been shown to interact with alpha-synuclein, which in turn is
      associated with Parkinson's disease. However, the function of synphilin-1 is
      unknown. We have cloned mouse synphilin in an attempt to describe conserved and
      therefore likely functional domains. The deduced amino acid sequence of the
      protein shows extensive homology with its human counterpart, with greatest
      similarities in those regions that contain ankyrin-like motifs and the coiled
      coil domain. Expression of mouse synphilin-1 across tissues is similar to its
      human counterpart and not limited to brain. The results show that the synphilin-1
      sequence and expression patterns are conserved across species.

PMID- 11958832
TI  - Caffeine's neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      toxicity shows no tolerance to chronic caffeine administration in mice.
AB  - We investigated the effect of chronic daily caffeine treatment on caffeine's
      neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      induced dopaminergic toxicity. Mice received either caffeine (20 mg/kg) or saline
      daily for 9 days. Caffeine-induced locomotion tolerance developed within 3 days
      of treatment and persisted for the duration of the experiment. On day 10, mice
      were treated with MPTP (20 mg/kg, x4). Caffeine (20 mg/kg) or saline was
      administered 10 min before each MPTP dose. Acute pretreatment with caffeine
      attenuated MPTP-induced loss of striatal dopamine and dopamine transporter
      binding sites, and this attenuation was identical in mice pretreated chronically
      with caffeine or with saline. Thus, in contrast to the locomotor stimulant effect
      of caffeine, its neuroprotectant effect did not show tolerance to prior caffeine
      exposure. These data raise the possibility that caffeine may induce
      neuroprotection and locomotion by distinct mechanisms.

PMID- 11958833
TI  - Prolonged depolarization of rat cerebral synaptosomes leads to an increase in
      vesicular glutamate content.
AB  - Glutamate accumulation into synaptic vesicles is a vital step in glutamate
      synaptic transmission. In this study, we have explored the possibility that
      vesicular glutamate storage may be subject to some regulation. Synaptosomes were
      depolarized and subjected to [3H] glutamate under non-depolarizing conditions,
      and vesicular [3H] glutamate content was determined by a filter-based assay. We
      present evidence here that prolonged depolarization of synaptosomes leads to an
      increase in vesicular glutamate content. Induction of this enhanced state is time
      and temperature-dependent. The enhanced state has two components, one readily
      reversible and the other long-lasting. The up-regulation of glutamate storage
      capacity could lead to an increase in quantal size and play a role in modulation
      of glutamate transmission efficiency.

PMID- 11958834
TI  - Local neurokinin-1 receptor in the knee joint contributes to the induction, but
      not maintenance, of arthritic pain in the rat.
AB  - Substance P is known to exert various pro-inflammatory effects that are mediated
      by neurokinin-1 (NK-1) receptor in peripheral tissues. This study examined the
      effect of the NK-1 receptor antagonist cis-2-[diphenylmethyl]-N-[(2-iodophenyl)-1
      azabicyclo[2.2.2]octan-3-amine] (L-703,606) on nociceptive response following
      carrageenan injection (2%, 50 microl) into the knee joint cavity of the right
      hind leg. L-703,606 injection (0.1 or 1 mM, 50 microl) into the same joint cavity
      immediately before the carrageenan injection significantly reduced the
      nociceptive response. However, antagonist treatment at 5 h after carrageenan
      injection was ineffective in alleviating nociception. Neither intraperitoneal
      injection of the antagonist (1 mM, 50 microl) immediately before the carrageenan
      injection was effective. These results suggest that local NK-1 receptor
      contributes to the induction, but not maintenance, of arthritic pain.

PMID- 11958835
TI  - mRNA expression alterations of inward rectifier potassium channels in rat brain
      with cholinergic impairment.
AB  - Potassium channel dysfunction has been indicated in Alzheimer's disease. In the
      present study, spatial memory, the activity of cortical acetylcholinesterase
      (AChE) and the expressions of inward rectifier potassium channels (Kir) were
      measured after ibotenic acid lesions of nucleus basalis magnocellularis (nbm) in
      rats. Expressions of Kir (Kir2.1, Kir3.1, Kir6.1 and Kir6.2) at mRNA level were
      assessed using reverse transcription-polymerase chain reaction. At 28 days after
      ibotenic acid injection, the spatial memory of rats was significantly impaired
      accompanied by a 32% reduction of cortical AChE activity. Furthermore, the
      expression of Kir6.2 was increased by 79.3% in cortex, and that of Kir6.1 was
      increased by 172.1% in hippocampus, while no obvious changes in the mRNA
      expression of Kir2.1 and Kir3.1 were detected. This study indicated that the
      expression of adenosine triphosphate-sensitive potassium channel was area and
      channel subtype specifically increased following nbm lesions.

PMID- 11958836
TI  - Nicotine administration decreases nitric oxide synthase expression in the
      hypothalamus of food-deprived rats.
AB  - Effect of nicotine on nitric oxide synthase (NOS) expression in various
      hypothalamic regions was investigated in rats via nicotineamide adenine
      dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Sprague-Dawley rats
      were divided into the fed group, the fed and nicotine-treated group, the food
      deprived group, and the food-deprived and nicotine-treated group. The fed groups
      received abundant food and water, while food was withheld from the food-deprived
      groups for 48 h. The nicotine-treated groups were injected with nicotine.
      Following food deprivation, enhanced NAPDH-d expression was detected in the
      paraventricular nucleus, ventromedial hypothalamic nucleus, and lateral
      hypothalamic area of the hypothalamus. Nicotine administration to the food
      deprived rats resulted in decreased NADPH-d positivity. The present results
      indicate that nicotine administration is effective in limiting the enhancement in
      NOS expression following food restriction.

PMID- 11958837
TI  - 6-Hydroxydopamine lesioning differentially affects alpha-synuclein mRNA
      expression in the nucleus accumbens, striatum and substantia nigra of adult rats.
AB  - The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion and/or repeated
      administration of levodopa (L-DOPA) to normal and 6-OHDA-lesioned rats on alpha
      synuclein mRNA expression was investigated by in situ hybridization
      histochemistry. A 6-OHDA lesion of the nigro-striatal pathway alone, confirmed by
      the loss of nigral tyrosine hydroxylase mRNA expression, markedly decreased alpha
      synuclein mRNA in the lesioned substantia nigra (SN). In contrast, the levels of
      alpha-synuclein mRNA in the denervated striatum and nucleus accumbens were not
      altered. Chronic administration of L-DOPA to normal or 6-OHDA-lesioned rats had
      no effect on alpha-synuclein mRNA expression in the SN, striatum or nucleus
      accumbens. These data confirm that alpha-synuclein is localized in the nigro
      striatal tract but that its gene expression is not regulated by dopamine.

PMID- 11958838
TI  - Activation of spinal extracellular signaling-regulated kinase-1 and -2 by
      intraplantar carrageenan in rodents.
AB  - We have examined the activation of spinal extracellular signaling-regulated
      kinase (ERK) in juvenile rats and adult mice after intraplantar carrageenan or
      saline and its relationship to pain behavior. In rats, intraplantar carrageenan
      evoked a peak five-fold activation of spinal ERK at 30 min measured by
      immunoblot. Saline injection resulted in a two-fold activation. This differential
      ERK activation correlated with a 2.5-fold greater pain response and the
      development of secondary hyperalgesia in carrageenan-injected rats, whereas both
      saline and carrageenan produced similar primary hyperalgesia. In mice,
      carrageenan injection produced a peak 3.5-fold activation of ERK, but saline was
      ineffective. We conclude that ERK activation may underlie spinal nociceptive
      processing and secondary hyperalgesia after carrageenan inflammation.

PMID- 11958840
TI  - Determination of acetylcholine and dopamine content in thalamus and striatum
      after excitotoxic lesions of the pedunculopontine tegmental nucleus in rats.
AB  - The pedunculopontine tegmental nucleus (PPTg) contains cholinergic neurons whose
      principal ascending connections are with thalamic nuclei and structures
      associated with the striatum. It has been hypothesized that PPTg neurons are more
      closely associated with the substantia nigra (and therefore striatal motor
      systems) than with the ventral tegmental area (and therefore limbic striatal
      functions). In the present experiments we have examined the hypothesis that the
      PPTg is similarly associated with motor nuclei in the thalamus. Rats received
      unilateral ibotenate lesions of PPTg and were sacrificed 1, 2, 4 or 7 days later.
      Discrete thalamic nuclei, and samples of caudate-putamen and nucleus accumbens,
      were punched out and thalamic acetylcholine (ACh) and striatal ACh and dopamine
      (DA) content examined. Anteroventral nucleus had decreased ACh content after PPTg
      lesion, but a time dependent increase was found in mediodorsal nucleus; ACh
      concentration was unchanged in thalamic reticular nucleus or medial geniculate.
      No long-term lesion-dependent changes in striatal ACh or DA content were found.
      The effects of PPTg lesion on thalamic ACh content are consistent with the
      hypothesis that it has effects on motor nuclei, but also indicate that PPTg
      lesions have complex and dynamic effects on thalamic ACh content.

PMID- 11958839
TI  - Nitric-oxide-synthase-mediated cyclic guanosine monophosphate production in
      neonatal rat cerebellar prisms is resistant to calcineurin inhibition.
AB  - Although the macrolide immunosuppressant tacrolimus (FK506) is neuroprotective in
      animal models of focal and global cerebral ischaemia, the mechanism of this
      action is not known. FK506 inhibits the protein phosphatase calcineurin, whose
      substrates can include nitric oxide synthase (NOS), and the neuroprotective
      effect of FK506 has been attributed to inhibition of NOS activity. We have
      examined nitric oxide-mediated cyclic guanosine monophosphate (cGMP) accumulation
      in neonatal rat cerebellar prisms. As expected, N-methyl-D-aspartate (NMDA)
      induced a rapid, concentration dependent accumulation of cGMP that was inhibited
      by the NMDA receptor antagonist dizocilpine (MK801) and the NOS inhibitor L-nitro
      arginine methyl ester. Phosphoserine immunopositivity following NMDA exposure was
      increased in the presence of FK506, confirming inhibition of calcineurin.
      However, FK506 had no effect on NMDA-stimulated cGMP accumulation. These findings
      suggest that the neuroprotective effect of FK506 may be mediated by mechanisms
      other than increased NOS phosphorylation.

PMID- 11958841
TI  - The effect of different morphological sampling criteria on the fraction of
      bursting cells recorded in the rat subiculum in vitro.
AB  - In spite of the large variability of the fraction of bursting cells reported in
      the subiculum (from 54 to 100%), this structure has been considered as
      intrinsically bursting. Here, using visually assisted whole-cell recordings and
      Neurobiotin labeling in vitro, we correlated the electrophysiological firing
      modes of subicular cells (bursting, regular-spiking and fast-spiking) with their
      morphological characteristics (somatic size and shape). We then examined how
      different morphological sampling criteria for patching affect cell
      classification. We found a dramatic variability in the fraction of bursting
      cells, which ranged from 30 to 76% depending on the sampling criteria. We discuss
      the implications of these findings for the notion of the subiculum as an
      intrinsically bursting structure.

PMID- 11958842
TI  - Partial denervation of the locus coeruleus projections by treatment with the
      selective neurotoxin DSP-4 potentiates the long-term effect of
      parachloroamphetamine on 5-hydroxytryptamine metabolism in the rat.
AB  - Pretreatment with N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP-4), a
      neurotoxin highly selective for the locus coeruleus (LC) projections, has
      recently been found to increase the vulnerability of dopaminergic nerve terminals
      to their selective neurotoxins. In the present study, combined treatment with a
      selective serotonergic (5-HT-ergic) neurotoxin parachloroamphetamine (PCA) at low
      doses (1 or 2 mg/kg) and a low dose of DSP-4 (10 mg/kg) led to larger decreases
      in 5-hydroxyindoleacetic acid (5-HIAA) levels in several brain regions than with
      either toxin alone. A reduction in 5-hydroxytryptamine (5-HT) turnover was
      observed only after the combined treatment with low doses of DSP-4 and PCA. When
      DSP-4 (10 mg/kg) was administered 2 months before PCA (2 mg/kg), the effect of
      PCA on cortical 5-HT levels was augmented, as was the effect on cortical and
      hypothalamic 5-HIAA levels. Conclusively, after limited alterations in the LC
      projections, there is an enhanced sensitivity of 5-HT-ergic nerve terminals to
      PCA.

PMID- 11958843
TI  - A mutation in the human neurofilament M gene in Parkinson's disease that suggests
      a role for the cytoskeleton in neuronal degeneration.
AB  - Parkinson's disease (PD) is a common neurodegenerative movement disorder
      characterized by the destruction of dopaminergic neurons of the substantia nigra.
      We have identified a new mutation (Gly336Ser) in the medium neurofilament subunit
      in a patient of French-Canadian origin with early onset severe PD. This finding
      suggests, for the first time, that aberrations in neuronal molecules involved in
      the cytoskeleton could lead to the development of the pathology seen in PD.

PMID- 11958844
TI  - Transient appearance of amyloid precursor protein plaques in the brain of
      thymectomized rats after human leptomeningeal cell grafts.
AB  - Cells cultured from Alzheimer disease leptomeninges or skin were grafted into the
      cortex of adult thymectomized rats. At 3 days post-implant, plaque-like
      aggregates were found in the cortex, corpus callosum, septum and caudate nucleus.
      These structures were immunopositive for human amyloid precursor protein (APP),
      human amyloid beta peptide (Abeta), cathepsin D, apolipoprotein E and ubiquitin.
      Aberrant tau+ neurites, reactive astrocytes and microglia were associated with
      many aggregates. Although birefringent amyloid occupied the central area of most
      aggregates, these structures had disappeared by l month post-implant. Abeta and
      APP produced by grafted non-neural human cells can penetrate rat brain and form
      plaque-like structures, which can be effectively cleared by the rat.

PMID- 11958845
TI  - Galanin-like peptide stimulates food intake in the rat.
AB  - We have isolated a novel hypothalamic peptide, Galanin-like peptide (GALP), as a
      ligand for galanin receptor subtype GalR2. To investigate the physiological role
      of GALP, we examined the effect of the intracerebroventricular administration of
      GALP and found that GALP induced food intakes. GALP had ten-fold the orexigenic
      activity of galanin. We also observed the anxiogenic-like behavior after the
      administration of 1 nmol GALP. These results suggest that GALP is a novel
      orexigenic and anxiogenic peptide.

PMID- 11958846
TI  - Enhancement of spike and wave discharges by microinjection of bicuculline into
      the reticular nucleus of rats with absence epilepsy.
AB  - The aim of this study was to demonstrate the effect of administration of gamma
      aminobutyric acid (GABA)(A) receptor antagonist, bicuculline, into the reticular
      nucleus of the thalamus (nRt) on spike and wave discharges (SWD) and
      cardiovascular regulation in conscious rats with genetic absence epilepsy. Rats
      were instrumented with guide cannulas for drug injection and extradural
      electrodes for electroencephalogram recording. After a 1 week recovery period,
      iliac arterial catheters were inserted for direct measurement of blood pressure
      and heart rate. Administration of bicuculline into the nRt produced increases in
      spontaneous SWD and failed to alter blood pressure and heart rate. These data
      suggest that GABA(A) receptors located within the nRt are involved in the
      incidence of SWD, whereas they do not seem to be involved in cardiovascular
      regulation of rats with genetic absence epilepsy.

PMID- 11958847
TI  - Beta-amyloid deposition in the brains of rats chronically infused with thiorphan
      or lipopolysaccharide: the role of ascorbic acid in the vehicle.
AB  - Beta-amyloid deposition and neuroinflammation are two important features of
      Alzheimer's disease (AD) that may influence its progression. Chronic infusion of
      lipopolysaccharide (LPS) into the rodent 4th ventricle reproduces many of the
      neurobiological changes seen in AD. Chronic infusion of ascorbic acid containing
      thiorphan, an inhibitor of the enzyme neprilysin that catabolizes beta-amyloid,
      into the hippocampus induces extracellular deposition of beta-amyloid fibrils. We
      investigated whether the combined presence of chronic neuroinflammation could
      exacerbate the deposition of beta-amyloid induced by thiorphan. The infusion of
      any solution containing ascorbic acid alone or with thiorphan or LPS increased
      the level of intraneuronal beta-amyloid immunoreactivity. Solutions that did not
      contain ascorbic acid were not associated with increased intraneuronal beta
      amyloid immunoreactivity. The role of neprilysin in the deposition of beta
      amyloid in AD brains remains undetermined.

PMID- 11958848
TI  - Effects of ambient odors on reaction time in humans.
AB  - The perception of odors is well identified as having strong emotional correlates.
      The effects of ambient odors on arousal level and task performance have also been
      suspected but remain poorly assessed in the literature. The present study
      compared the reaction times of subjects between ambient odor conditions (pleasant
      and unpleasant) and a no-odor condition. The results showed that the reaction
      time in simple tasks (responses to visual or auditory stimulation) significantly
      decreased in the ambient odor conditions (whatever the pleasantness of the odors)
      compared with the no-odor condition. These results underline the importance of
      the olfactory environment in human behavior.

PMID- 11958850
TI  - Neurons in the cortical taste area receive nociceptive inputs from the whole body
      as well as the oral cavity in the rat.
AB  - Almost all mechanoreceptive neurons in the cortical taste area (CTA) of the rat
      had receptive fields (RFs) in the oral cavity, except for a few neurons at the
      border with the primary somatosensory area that had RFs on the contralateral
      rhinarium or upper lip. About one-third of the mechanoreceptive neurons with RFs
      in the oral cavity had additional RFs on the tips of limbs, earflaps or tail,
      i.e. the glabrous skin or skin with sparse hairs of the external surface of the
      body (whole body type). Most of these neurons received both innocuous and noxious
      inputs (wide dynamic range type), but some had either type of input (low
      threshold mechanoreceptive or nociceptive specific type). Some nociceptive
      neurons were responsive to taste, as previously found. Nociceptive neurons with
      the whole body type of RFs were diffusely distributed across the CTA without
      clustering. The corticocortical afferents, probably originating from the visceral
      part of the insula, may code body condition to modulate the taste responsiveness
      of the cortical taste neurons.

PMID- 11958849
TI  - The tau H1 haplotype is associated with Parkinson's disease in the Norwegian
      population.
AB  - We investigated the association of Parkinson's disease (PD) with tau gene H1
      haplotypes in the Norwegian population. In a sample of 96 unrelated PD cases and
      68 control subjects, we observed an increased risk of PD for persons with the tau
      H1 haplotype (odds ratio=5.52; 95% confidence interval: 2.64-11.10; P=2.17x10(
      6)). Findings provide evidence that tau participates in the PD pathogenic process
      and demonstrate the value of isolated populations in mapping complex traits.

PMID- 11958851
TI  - Cardiac arrest cerebral ischemia model in mice failed to cause delayed neuronal
      death in the hippocampus.
AB  - Global cerebral ischemia models for genetically engineered mice are of particular
      importance for the study of delayed neuronal death, but have been complicated by
      variability of vascular anatomy. Here we developed a 5-min cardiac arrest model
      that was not affected by vascular anatomy, and evaluated the hippocampal neuronal
      injury in BL/6 and SV129 mice. Despite prolonged anoxic depolarization for
      approximately 7 min, however, no consistent ischemic neuronal injury was noted in
      the CA1 sector of the hippocampus in both strains. Thus, our observations
      suggested that murine hippocampal neurons are relatively resistant to ischemia
      compared with those in other rodents.

PMID- 11958852
TI  - Blockade of the antinociceptive effect of spinally administered kyotorphin by
      naltrindole in mice.
AB  - We investigated the role of spinal opioid receptors in the antinociceptive effect
      of kyotorphin (Tyr-Arg, KTP) by using an in vivo mice tail-pinch test and an in
      vitro opioid receptor binding assays. Intrathecal administration of KTP produced
      a dose-dependent antinociceptive effect with an ED(50) value of 24 microg/mouse.
      This antinociception, which was reversed by the KTP antagonist Leu-Arg, was
      completely blocked by naltrindole but not by naloxonazine, beta-funaltrexamine,
      or nor-binaltorphimine. The results from the binding study in vitro indicated
      that KTP bound to spinal KTP receptors but not to any opioid receptors in the
      mouse spinal cord. These results suggest that KTP-induced antinociception is
      mediated by binding to KTP receptors followed by an indirect activation of the
      delta-opioid receptors in the spinal cord.

PMID- 11958853
TI  - Norepinephrine depresses the capsaicin-evoked miniature excitatory postsynaptic
      currents in substantia gelatinosa of the rat spinal cord.
AB  - Capsaicin selectively excites nociceptive primary afferent fibers and increases
      the frequency of glutaminergic miniature excitatory postsynaptic currents
      (mEPSCs) in the substantia gelatinosa of the spinal dorsal horn. The whole-cell
      voltage-clamp recording technique was used to examine the effect of
      norepinephrine (NE) on the capsaicin-induced increase in the frequency of mEPSCs.
      In the presence of tetrodotoxin, bath application of capsaicin (1 microM)
      remarkably enhanced the frequency of mEPSCs (295+/-52% of control). Following
      pretreatment with NE (10 microM), the capsaicin-induced frequency facilitation of
      mEPSCs was significantly depressed to 151+/-17% of the control. NE-induced
      depression in capsaicin action was blocked by yohimbine, a selective alpha(2)
      adrenergic receptor antagonist, indicating that NE exerts depression by
      activating the alpha(2)-adrenergic receptor. As the postsynaptic action of NE has
      been precluded in the present study, the results suggest that NE inhibits
      nociceptive input at a presynaptic site, the primary afferent terminal, during
      the nociceptive transmission in the spinal dorsal horn.

PMID- 11958854
TI  - Cisplatin-induced peripheral neurotoxicity in rats reduces the circulating levels
      of nerve growth factor.
AB  - The pathogenesis of the neurotoxicity of most antineoplastic drugs is unknown.
      Recent reports suggest that changes in the circulating levels of nerve growth
      factor (NGF) might be related to the dorsal root ganglia sensory neuron damage
      induced by cisplatin (CDDP), the first member of a family of widely used and very
      effective platinum-derived anticancer agents. Using a well-characterized model of
      CDDP neurotoxicity, we demonstrated that the NGF circulating level decreased
      during chronic CDDP administration in close accordance with the clinical course
      and returned to normal levels after recovery from the neurotoxic damage.
      Moreover, these changes were restricted to NGF and did not involve other trophic
      factors of the same neurotrophin family. Our findings are in agreement with
      previous in vitro and in vivo results and further suggest that NGF plays a
      specific role in the course of CDDP-induced primary sensory neuron damage.

PMID- 11958855
TI  - Oligodeoxynucleotides induce brain inflammation in rats when infused
      intracerebroventricularly.
AB  - Antisense oligodeoxynucleotides (ODNs) can inhibit gene expression in a specific
      manner. However, several studies described problems with cerebral ODN
      application. Here, we investigated the immune effects (interleukin-6 (IL-6)
      release, cell invasion into cerebrospinal fluid (CSF) and brain parenchyma) of
      'non-sense' randomized ODNs with different counterions (NH(4)(+), Na(+)) and
      modifications (with or without thioat-backbone) which were administered
      intracerebroventricularly for 48 h using osmotic mini-pumps in a rat model. All
      animals receiving ODNs showed increased IL-6 levels in the CSF as well as cell
      invasion into the CSF and brain parenchyma (P<0.05). However, the use of thioat
      backbone and ammonium as the counterion induced the highest IL-6 levels (7210+/
      1696 pg/ml, P<0.05) and the highest cell numbers in the CSF (31.6+/
      15.5x10(5)/ml, P<0.05) as well as brain parenchyma (268.1+/-143.2 HIS-48+
      cells/mm(2), P<0.01; and 31.3+/-10.7 OX-6+cells/mm(2), P<0.05) compared with the
      other groups.

PMID- 11958856
TI  - Dendritic spine formation in response to progesterone synthesized de novo in the
      developing Purkinje cell in rats.
AB  - The cerebellar Purkinje cell (PC) is a typical site for neurosteroid formation.
      We have demonstrated that this neuron possesses intranuclear receptor for
      progesterone and actively synthesizes progesterone de novo from cholesterol only
      during rat neonatal life, when the formation of the cerebellar cortex occurs
      dramatically. In this study, we therefore analyzed the effect of progesterone on
      dendritic spine formation of the PC. In vitro studies using cerebellar slice
      cultures from newborn rats showed that progesterone increases the density of PC
      dendritic spines in a dose-dependent manner. This effect was blocked by the
      progesterone receptor antagonist, RU486. Furthermore, trilostane, a specific
      inhibitor of progesterone synthesis, inhibited the increase of spine density.
      These results suggest that progesterone can promote dendritic spine formation,
      and endogenous progesterone synthesized de novo in the developing PC may induce
      such an effect.

PMID- 11958857
TI  - Cat odour exposure increases the expression of wolframin gene in the amygdaloid
      area of rat.
AB  - The aim of the present study was to find the genes expressed in the amygdaloid
      area after exposure to cat odour. Cat odour exposure was used to induce the
      ethologically relevant fear response in male rats. The differential expression of
      genes was analyzed using the cDNA Representational Difference Analysis (RDA). The
      differentially expressed clones were identified by sequencing and database
      search. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to
      confirm the differences found by the RDA. Exposure of rats to cat odour induced
      avoidance of odour stimulus and suppressed the exploratory activity of animals.
      We found that during the cat odour exposure, several genes with various functions
      were activated in the amygdaloid area. Among the identified genes, we found the
      activation of the wolframin gene. RT-PCR confirmed quantitative elevation in the
      levels of wolframin transcripts in the amygdaloid area. This study supports the
      role of wolframin in the regulation of emotional behaviour.

PMID- 11958858
TI  - Inducible nitric oxide synthase and argininosuccinate synthetase: co-induction in
      brain tissue of patients with Alzheimer's dementia and following stimulation with
      beta-amyloid 1-42 in vitro.
AB  - In Alzheimer's disease (AD), amyloid plaques within the brain are surrounded by
      activated glial cells (microglia and astrocytes). The mechanisms of glial
      activation and its effect on disease progression are not fully understood.
      Growing evidence suggests that beta-amyloid (Abeta) peptide, a major constituent
      of the amyloid plaque, is critically involved in the induction of an inflammatory
      response. The goal of this study was to examine the role of Abeta in the
      pathogenesis of local inflammation and neuronal cell death. We found increased
      mRNA levels of inducible nitric oxide synthase (iNOS) and the arginine
      regenerating enzyme argininosuccinate synthetase (ASS) within cortices of AD
      patients suggesting high output NO production. In vitro, synthetic Abeta1-42 and
      to a lesser extent Abeta1-40 induced iNOS and ASS transcription with consecutive
      NO overproduction in mixed rat neuronal-glial cultures. Furthermore, Abeta
      stimulation lead to an increased release of inflammatory cytokines interleukin
      (IL)-1beta, IL-6 and tumor necrosis factor-alpha. Again, Abeta1-42 had a much
      more pronounced effect as compared to Abeta1-40. Our data suggest that Abeta1-42
      is a key mediator of glial activation and via the induction of inflammatory
      mediators may be a critical component of the neurodegenerative process in AD.

PMID- 11958860
TI  - The amyloid-beta peptide binds to cyclin B1 and increases human cyclin-dependent
      kinase-1 activity.
AB  - The pathological features of Alzheimer's disease include deposition of amyloid
      beta (Abeta) containing plaques and increases in the expression of cyclin
      dependent kinase (CDK) enzymes. Chemical inhibition of CDKs prevents the
      neurotoxicity of the Abeta peptide. The activity of these kinases requires the
      binding of a cyclin component to the catalytic enzyme component. This study
      characterizes direct interactions between Abeta and cyclin B1. Abeta fragments
      containing the cytotoxic 31-35 region could inhibit biotinylated Abeta binding to
      cyclin B1. The same cytotoxic Abeta fragments all increased CDK-1 phosphorylation
      of known substrates in a cell free system. The CDK-1 inhibitor olomoucine
      prevented the cytotoxicity of Abeta 31-35 containing peptides in differentiated
      human teratocarcinoma cell line, Ntera 2/cl-D1 (NT-2) neurons. These direct
      interactions between cyclin B1 and Abeta provide potential mechanisms for the
      cytotoxicity of the Abeta peptide.

PMID- 11958859
TI  - Postsynaptic and presynaptic GABA(B) receptor-mediated inhibition in rat
      superficial superior colliculus neurons.
AB  - It has been reported that GABA(B) receptors are abundantly expressed in the
      superficial superior colliculus (sSC). To elucidate the action of GABA(B)
      receptors in the sSC, we tested the effect of a specific GABA(B) receptor agonist
      baclofen on sSC neurons in slices obtained from rats (16-22 days postnatal) using
      the whole-cell patch clamp technique. Bath application of baclofen (10-30 microM)
      elicited hyperpolarization associated with an increase in potassium conductance
      in morphologically different types of neurons including putative excitatory and
      inhibitory neurons. In addition, baclofen presynaptically suppressed electrically
      induced excitatory postsynaptic currents and inhibitory postsynaptic currents.
      These effects of baclofen were antagonized by a specific GABA(B) receptor
      antagonist CGP55845A (1 microM). The results suggest that the GABA(B) receptors
      have an inhibitory action at both post- and pre-synaptic sites in the sSC.

PMID- 11958861
TI  - Distinct sleep-wake stages in rats depend differentially on age.
AB  - The objective was to study age-related changes in sleep-wake stages in the rat by
      using precise polyphysiograph criteria for stage identification. Cortical and
      hippocampal electroencephalogram, and ocular and myographic activities were
      recorded in young, middle-aged, and old male Wistar rats to define 6 stages:
      active and quiet wake (AW, QW); light and deep slow wave sleep (SWS: S1, S2);
      intermediate stage of sleep (IS); and paradoxical sleep (PS). The old rats
      displayed a decrease in S1, S2, and IS, accompanied by an enhancement of AW. No
      age changes were found for QW and PS. It is suggested that the consolidation of
      SWS is primarily disturbed in the old rats, which may lead to a facilitation of
      wake.

PMID- 11958862
TI  - Expression of poly(C)-binding proteins is differentially regulated by hypoxia and
      ischemia in cortical neurons.
AB  - Hypoxia and ischemia regulate the expression of several important genes at the
      level of transcription and of mRNA stability. Two isoforms of a 40-kDa poly(C)
      binding protein, previously identified as RNA-binding proteins, bind to a hypoxia
      inducible protein-binding site in the 3'-untranslated region of erythropoietin
      and tyrosine hydroxylase mRNAs and regulate mRNA stability. To determine if
      poly(C)-binding proteins show changes in expression -- which might regulate mRNA
      stability -- in hypoxic or ischemic neuronal cells, we examined poly(C)-binding
      protein 1 and poly(C)-binding protein 2 expression in hypoxic cortical neuron
      cultures and in rat cerebral cortex after focal ischemia. Reverse transcription
      polymerase chain reaction and western blotting showed hypoxic up-regulation of
      poly(C)-binding protein 1, and down-regulation of poly(C)-binding protein 2, mRNA
      and protein expression. Hypoxia-inducible expression of poly(C)-binding protein 1
      was mediated by p38 mitogen-activated protein kinase, while hypoxia-reducible
      expression of poly(C)-binding protein 2 was mediated by protein kinase C.
      Immunostaining showed that poly(C)-binding protein 1, but not poly(C)-binding
      protein 2, expression was increased in the ischemic boundary zone (penumbra) of
      the frontal cortex after 90 min of ischemia, and persisted for at least 72 h
      after reperfusion. These results demonstrate that poly(C)-binding protein 1 and
      poly(C)-binding protein 2 in cortical neurons are differentially affected by
      hypoxic/ischemic insults, suggesting that there are functional differences
      between poly(C)-binding protein isoforms. Since we observed no poly(C)-binding
      protein expression in astroglia, alternative mRNA stability mechanisms may exist
      in these cells.

PMID- 11958863
TI  - Intracellular accumulation of beta-amyloid(1-42) in neurons is facilitated by the
      alpha 7 nicotinic acetylcholine receptor in Alzheimer's disease.
AB  - Amyloid beta(1-42), a major component of amyloid plaques, binds with
      exceptionally high affinity to the alpha 7 nicotinic acetylcholine receptor and
      accumulates intracellularly in neurons of Alzheimer's disease brains. In this
      study, we investigated the possibility that this binding plays a key role in
      facilitating intraneuronal accumulation of amyloid beta(1-42). Consecutive
      section immunohistochemistry and digital imaging were used to reveal the spatial
      relationship between amyloid beta(1-42) and the alpha 7 receptor in affected
      neurons of Alzheimer's disease brains. Results showed that neurons containing
      substantial intracellular accumulations of amyloid beta(1-42) invariably express
      relatively high levels of the alpha 7 receptor. Furthermore, this receptor is
      highly co-localized with amyloid beta(1-42) within neurons of Alzheimer's disease
      brains. To experimentally test the possibility that the binding interaction
      between exogenous amyloid beta(1-42) and the alpha 7 receptor facilitates
      internalization and intracellular accumulation of amyloid beta(1-42) in
      Alzheimer's disease brains, we studied the fate of exogenous amyloid beta(1-42)
      and its interaction with the alpha 7 receptor in vitro using cultured,
      transfected neuroblastoma cells that express elevated levels of this receptor.
      Transfected cells exhibited rapid binding, internalization and accumulation of
      exogenous amyloid beta(1-42), but not amyloid beta(1-40). Furthermore, the rate
      and extent of amyloid beta(1-42) internalization was related directly to the
      alpha 7 receptor protein level, since (1) the rate of amyloid beta(1-42)
      accumulation was much lower in untransfected cells that express much lower levels
      of this receptor and (2) internalization was effectively blocked by alpha
      bungarotoxin, an alpha 7 receptor antagonist. As in neurons of Alzheimer's
      disease brains, the alpha 7 receptor in transfected cells was precisely co
      localized with amyloid beta(1-42) in prominent intracellular aggregates.
      Internalization of amyloid beta(1-42) in transfected cells was blocked by
      phenylarsine oxide, an inhibitor of endocytosis. We suggest that the
      intraneuronal accumulation of amyloid beta(1-42) in Alzheimer's disease brains
      occurs predominantly in neurons that express the alpha 7 receptor. In addition,
      internalization of amyloid beta(1-42) may be facilitated by the high-affinity
      binding of amyloid beta(1-42) to the alpha 7 receptor on neuronal cell surfaces,
      followed by endocytosis of the resulting complex. This provides a plausible
      explanation for the selective vulnerability of neurons expressing the alpha 7
      receptor in Alzheimer's disease brains and for the fact that amyloid beta(1-42)
      is the dominant amyloid beta peptide species in intracellular accumulations and
      amyloid plaques.

PMID- 11958865
TI  - Spatio-temporal heterogeneity and cell-specificity of long-term potentiation
      induced mRNA expression in the dentate gyrus in vivo.
AB  - Gene expression in neurones can vary in response to neuronal activation. In this
      study, to analyse the spatio-temporal dynamics of the transcriptional response of
      three genes following the induction of long-term potentiation within the entire
      dentate gyrus in vivo, two new complementary approaches based on in situ
      hybridisation were developed: three-dimensional reconstruction of the pattern of
      mRNA expression within the entire dentate gyrus; and radioactive co-detection of
      two mRNA species allowing quantification of two different mRNAs in the same brain
      section. Zif268, Homer and syntaxin 1B genes were studied, and their regulated
      expression was examined three times after the induction of long-term
      potentiation. Constitutive expression of each gene under control conditions was
      homogeneous, but the spatial distribution of mRNA was heterogeneous along the
      rostro-caudal axis of the dentate gyrus following the induction of long-term
      potentiation, and different for each gene. In addition, the intensity of each
      gene-specific pattern of expression varied over time following the induction of
      long-term potentiation. Our results reveal that long-term potentiation
      differentially modulates the expression of mRNA species in cells of the dentate
      gyrus depending on their position along the rostro-caudal axis, on the gene and
      on time. We suggest that there are several molecular mechanisms of long-term
      potentiation, differing from one cluster of cells of the dentate gyrus to
      another, or that the different signaling pathways involved in long-term
      potentiation are used with varying efficiencies by different cells.

PMID- 11958866
TI  - Seizure susceptibility and epileptogenesis are decreased in transgenic rats
      overexpressing neuropeptide Y.
AB  - Functional studies in epileptic tissue indicate that neuropeptide Y and some of
      its peptide analogs potently inhibit seizure activity. We investigated seizure
      susceptibility in transgenic rats overexpressing the rat neuropeptide Y gene
      under the control of its natural promoter. Seizures were induced in adult
      transgenic male rats and their wild-type littermates by i.c.v. injection of 0.3
      microg kainic acid or by electrical kindling of the dorsal hippocampus.
      Transgenic rats showed a significant reduction in the number and duration of
      electroencephalographic seizures induced by kainate by 30% and 55% respectively
      (P<0.05 and 0.01). Transgenic rats were also less susceptible to epileptogenesis
      than wild-type littermates as demonstrated by a 65% increase in the number of
      electrical stimuli required to induce stage 5 seizures (P<0.01). This phenotype
      was associated with a strong and specific expression of neuropeptide Y mRNA in
      area CA1, a brain area involved in the seizure network. We conclude that
      endogenous neuropeptide Y overexpression in the rat hippocampus is associated
      with inhibition of seizures and epileptogenesis suggesting that this system may
      be a valuable target for developing novel antiepileptic treatments.

PMID- 11958864
TI  - Calcineurin enhances L-type Ca(2+) channel activity in hippocampal neurons:
      increased effect with age in culture.
AB  - The Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin, modulates a
      number of key Ca(2+) signaling pathways in neurons, and has been implicated in
      Ca(2+)-dependent negative feedback inactivation of N-methyl-D-aspartate receptors
      and voltage-sensitive Ca(2+) channels. In contrast, we report here that three
      mechanistically disparate calcineurin inhibitors, FK-506, cyclosporin A, and the
      calcineurin autoinhibitory peptide, inhibited high-voltage-activated Ca(2+)
      channel currents by up to 40% in cultured hippocampal neurons, suggesting that
      calcineurin acts to enhance Ca(2+) currents. This effect occurred with Ba(2+) or
      Ca(2+) as charge carrier, and with or without intracellular Ca(2+) buffered by
      EGTA. Ca(2+)-dependent inactivation of Ca(2+) channels was not affected by FK
      506. The immunosuppressant, rapamycin, and the protein phosphatase 1/2A
      inhibitor, okadaic acid, did not decrease Ca(2+) channel current, showing
      specificity for effects on calcineurin. Blockade of L-type Ca(2+) channels with
      nimodipine fully negated the effect of FK-506 on Ca(2+) channel current, while
      blockade of N-, and P-/Q-type Ca(2+) channels enhanced FK-506-mediated inhibition
      of the remaining L-type-enriched current. FK-506 also inhibited substantially
      more Ca(2+) channel current in 4-week-old vs. 2-week-old cultures, an effect
      paralleled by an increase in calcineurin A mRNA levels. These studies provide the
      first evidence that calcineurin selectively enhances L-type Ca(2+) channel
      activity in neurons. Moreover, this action appears to be increased concomitantly
      with the well-characterized increase in L-type Ca(2+) channel availability in
      hippocampal neurons with age-in-culture.

PMID- 11958867
TI  - Postnatal development of the dopaminergic system of the striatum in the rat.
AB  - The dopaminergic innervation of the developing caudate-putamen (patches and
      matrix) and nucleus accumbens (shell and core) of the rat was examined with light
      and electron microscope immunocytochemistry, using antibodies against dopamine.
      Light microscopic analysis showed, in accordance with previous studies, that
      early in life, dopaminergic fibers were relatively thick and present throughout
      the striatum. Their distribution was heterogeneous, showing dense aggregations,
      the so-called dopamine islands. The pattern of innervation became more uniform
      during the third postnatal week with most of the dopamine islands no longer
      detectable. For electron microscopic analysis, parts of the caudate-putamen
      containing dopamine islands or matrix, and of the nucleus accumbens, from the
      shell and the core of the nucleus, were selected. This analysis revealed that
      symmetrical synapses between immunoreactive profiles and unlabeled dendritic
      shafts predominated throughout development but, at the late stages, symmetrical
      axospinous synapses also became a prominent feature. These findings indicate
      that: (1) although the caudate-putamen and the nucleus accumbens have different
      connections and functions, they exhibit similar types of dopaminergic synapses,
      and (2) the relatively late detection of dopaminergic axospinous synapses
      suggests that the development of the dopaminergic system in the striatum is an
      active process, which parallels the morphological changes of striatal neurons and
      may contribute to their maturation.

PMID- 11958868
TI  - Amygdaloid projections to ventromedial striatal subterritories in the primate.
AB  - The ventral striatum is the part of the striatum associated with reward and goal
      directed behaviors, which are mediated in part by inputs from the amygdala. The
      ventral striatum is divided into 'shell' and 'core' subterritories which have
      different connectional, histochemical and pharmacological properties. Behavioral
      studies also indicate that subterritories of the ventral striatum are
      differentially involved in specific goal-directed behaviors. The amygdala is a
      heterogeneous structure which has multiple nuclei involved in processing
      emotional information. While the existence of an amygdalostriatal pathway has
      long been established, the relationship between amygdaloid afferents and specific
      subterritories of the ventral striatum is not known. In this study we
      operationally defined the ventromedial striatum as the region receiving cortical
      inputs primarily from the orbital and medial prefrontal cortex. We placed
      retrograde tracer injections into subregions of the ventromedial striatum of
      macaques monkeys to determine the relative contribution of specific amygdaloid
      inputs to each region. Calbindin-D28k immunostaining was used to further define
      the shell subterritory of the ventromedial striatum. Based on these definitions,
      the amygdala innervates the entire ventromedial striatum, and has few to no
      inputs to the central striatum. The basal and accessory basal nuclei are the
      major source of input to the ventromedial striatum, innervating both the shell
      and ventromedial striatum outside the shell. However, a restricted portion of the
      dorsomedial shell receives few basal nucleus inputs. Afferent inputs from the
      basal nucleus subdivisions are arranged such that the parvicellular subdivision
      projects mainly to the ventral shell and core, and the magnocellular subdivision
      targets the ventral shell and ventromedial putamen. In contrast, the intermediate
      subdivision of the basal nucleus projects broadly across the ventromedial
      striatum avoiding only the dorsomedial shell. The shell has a specific set of
      connections derived from the medial part of the central nucleus and
      periamygdaloid cortex. Within the shell, the dorsomedial region is distinguished
      by additional inputs from the medial nucleus. The ventromedial caudate nucleus
      forms a unique transition zone with the shell, based on inputs from the
      periamygdaloid cortex. Together, these results indicate that subterritories of
      the ventromedial striatum are differentially modulated by amygdaloid nuclei which
      play roles in processing olfactory, visual/gustatory, multimodal sensory, and
      'drive'-related stimuli.

PMID- 11958869
TI  - In vivo metabolism and clearance of substance P and co-expressed tachykinins in
      rat striatum.
AB  - Neurons expressing the preprotachykinin A gene, which encodes the sequences of
      substance P, neurokinin A, neuropeptide gamma and neuropeptide K, exemplify
      peptide co-existence. Furthermore, there is also evidence that substance P
      fragments have biological activity. However, the relative contribution of each of
      these peptides to tachykinin signalling is still poorly understood. An important
      factor which will determine the characteristics of the signal mediated by co
      localised peptides is their clearance from the extracellular space. The striatum,
      in which tachykinins are present and exert neuromodulatory roles, can be used as
      a model to investigate this aspect. Therefore, in this study we characterised in
      vivo in the striatum the metabolism and clearance of substance P and of the other
      three co-expressed peptides. After intrastriatal administration of 1 pmol,
      tritiated substance P disappeared too rapidly for metabolites to be detected.
      However, when 10 nmol substance P and 1 pmol tritiated substance P were co
      injected, substance P(1-4) and substance P(1-7), which are biologically active,
      were detected as major metabolites. Under these conditions, the rate of decay of
      tritiated substance P was 0.2 nmol/min. The effects of the peptidase inhibitors
      thiorphan, bestatin and captopril suggested that neutral endopeptidase 24.11 and
      aminopeptidases were involved in primary substance P cleavages, whereas
      angiotensin-converting enzyme was involved in secondary cleavages. The monitoring
      of the decay of unlabelled substance P by high-performance liquid chromatography
      gave a rate of 0.16 nmol/min. Using high-performance liquid chromatography with
      capillary electrophoresis, the rates of decay of 10 nmol neurokinin A or
      neuropeptide gamma were five and seven times faster than that of substance P. In
      contrast, over the time course of the experiment, no significant decay of
      neuropeptide K was detected. These results show that substance P disappears
      rapidly from the extracellular space, and supports the formation in vivo of major
      N-terminal active substance P metabolites. Our study also highlights significant
      differences in the clearance of co-expressed tachykinins and suggests that
      certain species may disappear relatively slowly from the extracellular space, and
      thus may make a significant temporal and spatial contribution to signalling.

PMID- 11958870
TI  - Nicotinic cholinergic activation of magnocellular neurons of the hypothalamic
      paraventricular nucleus.
AB  - The aim of the present work was to determine whether paraventricular neurons
      possess functional acetylcholine nicotinic receptors. Using infrared
      videomicroscopy and differential interference contrast optics, we performed whole
      cell recordings in hypothalamic slices containing the paraventricular nucleus.
      Acetylcholine, locally applied by pressure microejection in the presence of the
      muscarinic antagonist atropine, evoked a rapidly rising inward current in
      paraventricular magnocellular endocrine neurons. This current persisted in the
      presence of blockers of synaptic transmission. It could be reversibly suppressed
      by nanomolar concentrations of methyllycaconitine, a selective antagonist of
      alpha 7-containing nicotinic receptors, but was insensitive to micromolar
      concentrations of dihydro-beta-erythroidine, an antagonist acting preferentially
      on non-alpha 7 nicotinic receptors. In addition, the effect of acetylcholine
      could be mimicked by exo-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane, a recently
      synthesized nicotinic agonist specific for alpha 7 receptors. Acetylcholine also
      desensitized paraventricular nicotinic receptors. Desensitization was pronounced
      and recovery from desensitization was rapid, consistent with the notion that
      paraventricular nicotinic receptors contain the alpha 7 subunit. Nicotinic
      currents could not be evoked in paraventricular parvocellular neurons, suggesting
      that these neurons are devoid of functional nicotinic receptors. The
      electrophysiological data were corroborated by light microscopic autoradiography,
      showing that [(125)I]alpha-bungarotoxin binding sites are present in all the
      magnocellular divisions of the paraventricular nucleus but are undetectable in
      other areas of this nucleus. Immunohistochemistry, performed using antibodies
      directed against vasopressin and oxytocin, indicated that responsiveness to
      nicotinic agonists was a property of vasopressin as well as of oxytocin
      magnocellular endocrine neurons, in both the paraventricular and the supraoptic
      nucleus. We conclude that nicotinic agonists can influence the magnocellular
      neurosecretory system by directly increasing the excitability of magnocellular
      neurons. By contrast, they are probably without direct effects on paraventricular
      parvocellular neurons.

PMID- 11958871
TI  - Differential regulation of pituitary adenylate cyclase-activating peptide
      receptor variants in the rat suprachiasmatic nucleus.
AB  - Pituitary adenylate cyclase-activating peptide is densely distributed in the
      suprachiasmatic nucleus, which functions as the circadian pacemaker. A receptor
      for pituitary adenylate cyclase-activating peptide, denoted as PAC(1), exists in
      six variant forms. We used reverse transcriptase-polymerase chain reaction to
      identify the PAC(1) variants that are expressed in the suprachiasmatic nucleus.
      Dominant variant forms of PAC(1) in the suprachiasmatic nucleus were PAC(1)short,
      PAC(1)hip, and PAC(1)hop1. By in situ hybridization, we examined 24-h profiles of
      mRNAs for the identified receptor variants in the suprachiasmatic nucleus in
      constant darkness and during the light-dark cycle. In constant darkness there
      were clear circadian rhythms in PAC(1)short mRNA with a peak at circadian time 4
      but no rhythmicity was observed in PAC(1)hip mRNA or PAC(1)hop1 mRNA. In light
      dark cycles, on the other hand, PAC(1)hip mRNA displayed a bimodal rhythm with
      troughs at zeitgeber time 4 and 16 but PAC(1)hop1 mRNA stayed constant during the
      day. These results suggest that PAC(1) splice variants are differentially
      regulated in the rat suprachiasmatic nucleus.

PMID- 11958872
TI  - Interaction between neuropeptide FF and opioids in the ventral tegmental area in
      the behavioral response to novelty.
AB  - Considerable evidence has focused on the interaction between endogenous opioid
      peptides and the dopaminergic mesocorticolimbic system in behavioral responses to
      stress. Recently, it has been proposed that the CNS synthesizes and secretes
      neuropeptides that act as part of a homeostatic system to attenuate the effects
      of morphine or endogenous opioid peptides. Among these antiopioids, neuropeptide
      FF (NPFF) is particularly interesting since both NPFF immunoreactive-like
      terminals and NPFF binding sites are located in the vicinity of the dopaminergic
      cell bodies within the ventral tegmental area (VTA) suggesting an interaction at
      this level. The purpose of the present study was to evaluate the respective
      implication of opioid and antiopioid peptides at the level of the VTA in the
      locomotor response to novelty in rats. The results indicate that s.c. naloxone
      pretreatment, an opiate receptor antagonist, reduced locomotor activity in rats
      placed in a novel environment without having any effect in a familiar
      environment. This effect takes place in the VTA since intra-VTA administration of
      naloxone methobromide diminished similarly and dose-dependently the motor
      response to novelty. This effect is mainly dependent on opioid peptides released
      at VTA level since local injections of thiorphan, an inhibitor of enkephalin
      degradation, strongly increased locomotor response to novelty and this effect is
      completely prevented by the co-administration of naloxone methobromide. When
      injected in the VTA, NPFF is acting as an antiopioid compound, i.e. it reduces
      the locomotor activity triggered by exposure to novelty to the level recorded in
      a familiar environment. Moreover, NPFF decreased dose-dependently the
      potentiation of novelty-induced locomotor response produced by VTA injection of
      thiorphan. Taken together, these results suggest that NPFF neurons may
      participate at the level of the VTA to a homeostatic regulating process
      counteracting opioid effects induced by a mild stress such as novelty.

PMID- 11958874
TI  - Characterisation of the calcium responses to histamine in capsaicin-sensitive and
      capsaicin-insensitive sensory neurones.
AB  - Adult rat sensory neurones were maintained in short-term tissue culture and their
      response to histamine was studied by monitoring changes in intracellular [Ca(2+)]
      with Fura-2. The proportion of histamine-sensitive neurones increased as the
      concentration increased from 10 microM to 10 mM. The fraction of responding cells
      did not change significantly over the first week in culture. About 60% of
      histamine-sensitive cells were insensitive to capsaicin and these cells tended to
      be of small diameter. The integrated calcium response to histamine was greatest
      at 100 microM when the response consisted of two phases: an initial short-lasting
      transient followed by a sustained plateau that was dependent on extracellular
      calcium. This response was blocked by the histamine H(1) receptor antagonist
      mepyramine but not by cimetidine or thioperamide which block H(2) and H(3)
      receptors, respectively. Moreover, application of histamine increased the
      intracellular concentration of inositol 1,4,5-trisphosphate -- an effect blocked
      by mepyramine. These data show that the response is mediated by H(1) receptors.
      The phospholipase C inhibitor U73122 blocked the response to 100 microM histamine
      and significantly reduced the fraction of cells responding to 1 mM and 10 mM
      histamine as did removal of extracellular calcium. A combination of U73122 and
      calcium-free medium abolished all responses to histamine. These data suggest that
      in addition to activating phospholipase C, high concentrations of histamine gate
      an influx of calcium that is independent of store depletion. The implications of
      these results for the transduction of pruritic stimuli is discussed.

PMID- 11958873
TI  - Nociceptive afferents selectively modulate the cardiac component of the
      peripheral chemoreceptor reflex via actions within the solitary tract nucleus.
AB  - Our previous findings showed that the nucleus of the solitary tract (NTS)
      mediated part of the tachycardia evoked during somatic noxious stimulation. Here,
      we investigated the interaction between somatic nociceptor- and peripheral
      chemoreceptor-evoked cardiac changes. We sought to determine whether this
      interaction occurred within the NTS, the primary site of termination of
      chemoreceptor afferents. In a working heart-brainstem preparation of rat,
      mechanical noxious activation of a forelimb evoked a tachycardia of 17.5+/-3
      (mean+/-S.E.M.) b.p.m., whereas sodium cyanide (7-30 microg) stimulation of
      peripheral chemoreceptors produced a sub-maximal bradycardia of -140+/-15 b.p.m.
      During nociceptor stimulation the sodium cyanide-evoked bradycardia was
      attenuated to -42.6+/-12 b.p.m. but could be prevented by a multiple bilateral
      NTS microinjection of bicuculline (i.e. -173+/-18 b.p.m.). Furthermore, the
      activity of NTS neurones responding to peripheral chemoreceptor stimulation
      increased from 2.8+/-1.3 to 9.4+/-1.9 Hz during sodium cyanide injection (n=7;
      P<0.01). The latter response was attenuated reversibly to 2.9+/-0.9 Hz during
      simultaneous stimulation of the brachial nerve. Pressure ejection of bicuculline
      abolished this inhibitory action of brachial-nerve stimulation on the
      chemoreceptor-evoked excitatory synaptic response. We conclude that somatic
      noxious stimulation attenuates the chemoreceptor reflex-evoked bradycardia via a
      GABA(A)ergic mechanism in the NTS.

PMID- 11958875
TI  - Neurokinin-1 and neurokinin-3 receptors are expressed in vagal efferent neurons
      that innervate different parts of the gastro-intestinal tract.
AB  - Vagal efferent neurons innervating the digestive tract are mainly contained in
      the dorsal motor nucleus of the vagus. Previous studies have suggested that
      neurokinins and their neurokinin-1 and neurokinin-3 receptors are involved in the
      parasympathetic control of digestive functions. The purpose of the present study
      was to analyze the distribution of neurokinin-1 and neurokinin-3 receptors
      amongst vagal efferent neurons innervating the stomach, the duodenum, the ileum
      and the cecum. The immunocytochemical detection of neurokinin-1 and neurokinin-3
      receptors was combined with the immunocytochemical detection of retrogradely
      transported cholera toxin-B subunit, previously injected in the gut wall.
      Neurokinin-1 and neurokinin-3 receptors were present in 19+/-7% and 8+/-3% of
      retrogradely labeled neurons innervating the stomach. Almost half of the labeled
      neurons innervating the duodenum (46+/-7%) expressed neurokinin-1 receptors but
      less than 0.5% contained neurokinin-3 receptors. None of the retrogradely labeled
      vagal efferent neurons innervating the ileum and the cecum were immunoreactive
      for neurokinin-1 and neurokinin-3 receptors. We conclude that neurokinin-1 and
      neurokinin-3 receptors are located on vagal efferent neurons which innervate the
      stomach and that neurokinin-1 receptors are common, whereas neurokinin-3
      receptors are rare on neurons projecting to the duodenum. Additionally, the
      distal part of the rat small intestine is innervated by vagal efferent neurons
      that do not express neurokinins receptors on their membrane. This suggests that
      neurokinins may influence the parasympathetic control of different regions of the
      gastro-intestinal tract in specific ways.

PMID- 11958876
TI  - Cutaneous sympathetic motor rhythms during a fever-like response induced by
      prostaglandin E(1).
AB  - Neuronal population discharges within the CNS and in somatic and sympathetic
      motor nerves often display oscillations. Peripheral oscillations may provide a
      window into central mechanisms, as they often show coherence with population
      activity of subsets of central neurones. The reduction in heat loss through the
      cutaneous circulation during fever may be mediated via sympathetic premotor
      neurones not utilised during normal temperature regulation. Consequently, here we
      assessed, in anaesthetised rats, whether the frequency signature of population
      sympathetic discharge observed in neurones innervating the tail
      (thermoregulatory) circulation changed during a fever-like response induced by
      intracerebroventricular injection of prostaglandin E(1). We found that when core
      temperature was raised to 38.8-40.5 degrees C sympathetic activity was abolished.
      Following administration of prostaglandin (400 ng or 1 microg per rat), activity
      was restored to levels seen prior to heating (154+/-53.5%; n=10). Injection of
      vehicle had no effect (n=7). Prior to heating when most animals were in central
      apnoea (14/18) two peaks were observed in autospectra of sympathetic activity:
      one at 0.68-0.93 Hz (T-peak) and another at the frequency of ventilation (2 Hz).
      Central respiratory drive was recruited during hyperthermia where it was 1:2
      locked to the frequency of ventilation and following prostaglandin
      administration, an additional peak in sympathetic autospectra was seen at this
      frequency. Time-evolving spectra indicated that this peak resulted from the
      dynamic locking of the 'T-peak' to central respiratory drive. Our data show that
      during a fever-like response the dominant oscillations in sympathetic activity
      controlling a thermoregulatory circulation and their dynamic coupling to
      respiratory-related inputs are similar to those seen under normal conditions.
      Therefore, during this fever-like response, the neural substrate(s) underlying
      the oscillations is not reconfigured and remains capable of sculpturing the
      pattern of sympathetic neuronal discharge that may be regulated by several
      descending pathways.

PMID- 11958877
TI  - Responses of myenteric S neurones to low frequency stimulation of their synaptic
      inputs.
AB  - Previous experiments have shown that prolonged low frequency stimulation of
      presynaptic inputs causes excitation of AH neurones that considerably outlasts
      the period of stimulation in the guinea-pig small intestine. The present
      experiments compare the responses of S neurones (which are motor neurones and
      interneurones) with responses of AH neurones (intrinsic primary afferent
      neurones) to low frequency stimulation of synaptic inputs. Neurones in the
      myenteric plexus of isolated segments of guinea-pig small intestine were recorded
      from with intracellular microelectrodes. During their impalement, the neurones
      were filled with a marker dye and they were later processed to reveal their
      shapes and immunohistochemical properties. One group of neurones, inhibitory
      motor neurones to the circular muscle, was depolarised by stimulation of synaptic
      inputs at 1 Hz for 100 s to 4 min. With 4-min trains of stimuli, peak
      depolarisation was 21+/-2 mV (mean+/-S.E.M.), which was reached at about 110 s.
      Depolarisation was accompanied by increased excitability; before stimulation, a
      test intracellular pulse (500 ms) triggered 3 action potentials, at the peak of
      excitability this reached 16 action potentials. Depolarisation began to decline
      immediately at the end of stimulation. This contrasts with responses of AH
      neurones, in which depolarisation persisted after the end of the stimulus (peak
      depolarisation at 300 s). The excitation and depolarisation of inhibitory motor
      neurones was blocked by the neurokinin 1 tachykinin receptor antagonist, SR140333
      (100 nM), but excitation of AH neurones was not affected. Small or no responses
      to 1 Hz stimulation were recorded from descending filamentous interneurones,
      longitudinal muscle motor neurones and excitatory circular muscle motor neurones.
      In conclusion, this study indicates that sustained slow postsynaptic excitation
      only occurs in AH neurones, and that one type of S neurones, inhibitory motor
      neurones to the circular muscle, responds substantially, but not beyond the
      period of stimulation, to activation of synaptic inputs at 1 Hz. This slow
      excitatory postsynaptic potential evoked by low frequency stimulation is mediated
      by tachykinins.

PMID- 11958878
TI  - Differential discrimination of fast and slow synaptic waveforms by two low
      voltage-activated calcium channels.
AB  - Electrophysiological analysis of human embryonic kidney 293 cells stably
      expressing recombinant channels was used to compare how the biophysical
      properties of the low-voltage-activated Ca(2+) channels encoded by the alpha(1G)
      (Ca(V)3.1) or alpha(1I) (Ca(V)3.3) subunits shape their responses to excitatory
      synaptic potentials. In medium containing 2 mM extracellular Ca(2+) standard
      current-voltage relationships demonstrated both channel types to be clearly low
      voltage activated with significant slowly activating current responses being
      observed at -66 mV. At all test potentials examined, activation of Ca(V)3.3 was
      substantially slower than that of Ca(V)3.1. To probe how these different T-type
      channels might respond to excitatory postsynaptic potentials (EPSPs), mock EPSPs
      with different kinetic profiles were created from the sum of exponentials. These
      waveforms were then used as command templates in voltage-clamp experiments.
      Ca(V)3.1-mediated channels responded effectively to both rapidly decaying mock
      EPSPs and slowly decaying EPSPs. In contrast, Ca(V)3.3-mediated channels were
      poorly gated by rapidly decaying EPSPs but were effectively activated by the more
      prolonged synaptic response. When activated with mock EPSPs Ca(V)3.3-mediated
      currents were more resistant to steady-state depolarisation of the pre-stimulus
      holding potential. Ca(V)3.3 currents were also more resistant to repetitive
      application of prolonged EPSPs, which caused substantial inactivation of Ca(V)3.1
      mediated currents. The addition of a single mock action potential to the peak of
      a rapidly decaying EPSP voltage-clamp template greatly enhanced the currents
      produced by either Ca(V)3.1 or Ca(V)3.3-expressing cells. This facilitatory
      effect was considerably greater for Ca(V)3.3-mediated channels. From these data
      we suggest that the slow activation kinetics of Ca(V)3.3-mediated T-type channels
      enable them to respond selectively to either slow or suprathreshold synaptic
      potentials.

PMID- 11958879
TI  - MR imaging for prostate cancer staging: beauty or beast?

PMID- 11958880
TI  - Relationship between prostate volume, prostate-specific antigen nadir, and
      biochemical control.
AB  - PURPOSE: In patients treated with definitive three-dimensional conformal
      radiotherapy (3D-CRT) for localized prostatic adenocarcinoma, we sought to
      evaluate the relationship between pretreatment prostate gland volume and
      posttreatment prostate-specific antigen (PSA) nadir, as well as the relationship
      of prostate volume and PSA nadir with biochemical control (bNED). Two subgroups
      were studied: favorable (PSA <10 ng/mL, Gleason score 2-6, and T1-T2A) and
      unfavorable (one or more: PSA >/=10 ng/mL, Gleason score 7-10, T2B-T3). MATERIALS
      AND METHODS: A total of 655 men (n = 271 favorable and 384 unfavorable) were
      treated with 3D-CRT alone between May 1989 and November 1997. All patients had
      information on prostate volume and a minimum follow-up of 24 months (median 56,
      range 24-126). Of the 655 men, 481 (n = 230 favorable and 251 unfavorable)
      remained bNED at time of analysis, with biochemical failure defined in accordance
      with the American Society for Therapeutic Radiology and Oncology consensus
      definition. Factors analyzed for predictors of bNED included pretreatment
      prostate volume, posttreatment PSA nadir, pretreatment PSA, palpation T stage,
      Gleason score, center of the prostate dose, and perineural invasion (PNI). We
      also analyzed pretreatment prostate volume and its correlation to prognostic
      factors. For bNED patients, the relationship between PSA nadir and prostate
      volume was evaluated. RESULTS: On multivariate analysis, prostate volume (p =
      0.04) and palpation T stage (p = 0.02) were the only predictors of biochemical
      failure in the favorable group. On multivariate analysis of the unfavorable
      group, pretreatment PSA (p <0.0001), Gleason score (p = 0.02), palpation T stage
      (p = 0.009), and radiation dose (p <0.0001) correlated with biochemical failure,
      and prostate volume and PNI did not. For all 481 bNED patients, a positive
      correlation between pretreatment volume and PSA nadir was demonstrated (p
      <0.0001). Subgroup analysis of the favorable and unfavorable patients also
      demonstrated a positive correlation between prostate volume and PSA nadir (p =
      0.003 and p = 0.0002, respectively). Using multiple regression analysis, the
      following were found to be predictive of PSA nadir in all bNED patients: prostate
      volume (p <0.0001), pretreatment PSA (p <0.0001), palpation T stage (p = 0.0002),
      and radiation dose (p = 0.0034). Gleason score and PNI were not predictive. For
      the favorable group, palpation T stage (p = 0.0006), pretreatment PSA (p =
      0.0083), prostate volume (p = 0.0186), and Gleason score (p = 0.0592) were
      predictive of PSA nadir, and PNI and radiation dose were not predictive. In the
      unfavorable group, prostate volume (p = 0.0024), radiation dose (p = 0.0039),
      pretreatment PSA (p = 0.0182), and palpation T stage (p = 0.0296) were predictive
      of PSA nadir, and Gleason score and PNI were not predictive. CONCLUSION: This
      report is the first demonstration that prostate volume is predictive of PSA nadir
      for patients who are bNED in both favorable and unfavorable subgroups. PSA nadir
      did not correlate with bNED status in the favorable patients, but it was strongly
      predictive in the unfavorable patients. Prostate gland volume was also predictive
      of bNED failure in the favorable but not the unfavorable group.

PMID- 11958881
TI  - Erectile function after permanent prostate brachytherapy.
AB  - PURPOSE: To determine the incidence of potency preservation after permanent
      prostate brachytherapy using a validated patient-administered questionnaire and
      to evaluate the effect of multiple clinical and treatment parameters on penile
      erectile function. MATERIALS AND METHODS: Four hundred twenty-five patients
      underwent permanent prostate brachytherapy from April 1995 to October 1999. Two
      hundred nine patients who were potent before brachytherapy and who at the time of
      the survey were not receiving hormonal therapy were mailed the specific erectile
      questions of the International Index of Erectile Function (IIEF) questionnaire
      with a self-addressed stamped envelope. The questionnaire consisted of 5
      questions, with a maximal score of 25. Of the 209 patients, 181 (87%) completed
      and returned the questionnaire. The mean and median follow-up was 40.4 +/- 14.9
      and 40.6 months, respectively (range 19-75). Preimplant erectile function was
      assigned using a three-tiered scoring system (2 = erections always or nearly
      always sufficient for vaginal penetration; 1 = erections sufficient for vaginal
      penetration but considered suboptimal; 0 = the inability to obtain erections
      and/or erections inadequate for vaginal penetration). Postimplant potency was
      defined as an IIEF score >/=11. The clinical parameters evaluated for erectile
      function included patient age, preimplant potency, clinical T-stage, pretreatment
      prostate-specific antigen level, Gleason score, elapsed time after implantation,
      hypertension, diabetes mellitus, and tobacco consumption. Treatment parameters
      included radiation dose to the prostate gland, use of hormonal manipulation, use
      of supplemental external beam radiotherapy (EBRT), choice of isotope, prostate
      volume, and planning volume. The efficacy of sildenafil citrate in brachytherapy
      induced erectile dysfunction (ED) was also evaluated. RESULTS: Pretreatment
      erectile function scores of 2 and 1 were assigned to 125 and 56 patients,
      respectively. With a 6-year follow-up, 39% of patients maintained potency after
      prostate brachytherapy, with a plateau on the potency preservation curve.
      Postimplant preservation of potency (IIEF >/=11) correlated with preimplant
      erectile function (50.4% vs. 13.2% for preimplant scores of 2 and 1,
      respectively, p <0.001), patient age (57.4%, 38.2%, and 21.9% for patients <60,
      60-69, and >/=70 years old, respectively, p <0.004), use of supplemental EBRT
      (52.0% vs. 26.4% for patients without and with EBRT, p <0.001), and a history of
      diabetes mellitus (41.4% vs. 0% for patients without and with diabetes,
      respectively, p = 0.017). In multivariate analysis, clinical stage, radiation
      dose to the prostate gland, hormonal manipulation, choice of isotope, history of
      hypertension, and tobacco consumption had no effect on the ultimate preservation
      of potency. Only the preimplant potency score, use of supplemental EBRT, and
      diabetes maintained statistical significance. Sixty-two patients used sildenafil,
      with 53 (85%) reporting a favorable response. When potent patients were grouped
      with the ED patients who used sildenafil, the 6-year actuarial rate of potency
      preservation was 92%. Including the 70 impotent patients who never used
      sildenafil, the actuarial 6-year rate of potency preservation with and without
      pharmacologic support was 54% and 39%, respectively. CONCLUSION: Our results
      suggest that brachytherapy-induced ED is more common than previously reported and
      may be the result of obtaining patient information by means of a validated
      quality-of-life instrument by mail and not by personal interview. In multivariate
      analysis, only pretreatment potency, supplemental EBRT, and diabetes maintained
      statistical significance. Most patients with brachytherapy-induced ED responded
      favorably to sildenafil. Although the 6-year actuarial incidence of potency
      preservation was 39%, 52% of patients not receiving supplemental EBRT maintained
      potency. In addition, with pharmacologic support, 92% of patients maintained
      potency.

PMID- 11958883
TI  - Radiation-induced changes in cellularity and proliferation in human oral mucosa.
AB  - PURPOSE: To quantify the oral mucosal cell density and proliferation rate during
      conventional radiotherapy of head-and-neck tumors and to compare these parameters
      with clinical scoring of oral mucositis. MATERIALS AND METHODS: Between 1996 and
      1999, 22 patients were included in this study. Mucosal biopsies were taken before
      or during the radiotherapy course (5 x 2 Gy/wk). Biopsies were incubated in vitro
      with tritiated thymidine immediately after excision to label DNA-synthesizing
      cells. RESULTS: Epithelial cell density followed a biphasic radiation response. A
      steep decrease to about 50% of the preirradiation value (1000 cells/mm
      epithelium) during Week 1 was followed by a more gradual loss to about 400 cells
      at the end of treatment. The initial phase was based on the depression of
      proliferation, with 5-10 labeled cells/mm at the end of Week 1 vs. 60 labeled
      cells/mm in controls. Subsequently, proliferation was partially restituted at 20
      labeled cells/mm. A significant difference in cell numbers was seen between
      Radiation Therapy Oncology Group/European Organization for Research and Treatment
      of Cancer Grade 0 (approximately 850 cell/mm) and Grade 2 (325/mm) or Grade 3
      (370/mm). No significant differences were observed between reaction grades 1, 2,
      and 3. CONCLUSION: Conventionally fractionated radiotherapy induces a rapid
      suppression in cell production in Week 1, which results in a prompt reduction in
      cell numbers. Subsequently, a partial restoration of proliferation significantly
      reduces the rate of cell loss. These processes clearly precede the clinical
      response. Regeneration, defined as restoration of cellularity, is already under
      way when the maximal clinical response is observed. Clinical reaction grading
      corresponds poorly to cellular density measures during conventional
      fractionation.

PMID- 11958882
TI  - The role of endorectal coil MRI in patient selection and treatment planning for
      prostate seed implants.
AB  - PURPOSE: To assess the role of endorectal coil magnetic resonance imaging (MRI)
      staging for patients undergoing seed implantation (SI) with or without external
      beam radiotherapy (EBRT). MATERIALS AND METHODS: Between October 1994 and
      December 1998, 390 patients underwent prostate SI (98% Pd-103, 2% I-125). Seventy
      six percent of patients had a prostate serum antigen (PSA) < 10, 17% had PSA of
      10-20, and 7% of patients had PSA of > 20. Ten percent of patients had a Gleason
      score (GS) of 4-5, 54% had GS 6, 29% had GS 7, and 7% had GS >/= 8. Monotherapy
      was employed in 46% of patients, and the remaining 54% received combined EBRT and
      SI. Three hundred twenty-seven were staged by high-resolution phased array pelvic
      coil, or in most cases, an endorectal coil MRI. The MRI findings were used to
      guide stage-appropriate treatment recommendations, and to assist in the
      preplanning and optimization of seed distributions. The criteria utilized to
      determine MRI-based stage were founded on the reported literature from the
      University of Pennsylvania. All MRI studies were reviewed by C.A., D.B., or W.H.,
      who were unaware of clinical stage at the time of their review. The biopsy report
      was available to them as the only clinical correlate. RESULTS: Of the 327
      patients staged by MRI, 70% were upstaged from the digital rectal examination
      based clinical stage; 26% of T(1), T(2) patients were upstaged to T(3).
      Perineural invasion and the percentage of positive cores predicted for T(3) MRI
      stage (p < 0.0001 for both variables). MRI findings changed the overall treatment
      recommendation in 60/327 (18%) patients. The majority of these patients were
      advised to receive combined therapy instead of monotherapy after the MRI
      documented more extensive disease. The seed distribution was modified in 183/327
      (56%) patients, mostly related to preplanned extracapsular coverage of bulky or
      extraprostatic disease seen on MRI. With a mean follow-up of 38 months (range 3
      72), PSA freedom from progression (FFP) was 94% at 5 years. Cox regression
      analysis showed that only the percentage of positive cores (p = 0.001) and
      failure to have MRI staging (p = 0.0008) predicted for failure. Pretreatment PSA
      level, Gleason score, perineural invasion, and external beam radiotherapy did not
      significantly predict for PSA failure. We compared our MRI T(3) intermediate-risk
      group patients treated by combined therapy with a previous study of T(3)
      intermediate-risk group treated by radical prostatectomy (RP) at the University
      of Pennsylvania. Our 36-month PSA FFP was 94% compared with 21% for the previous
      study's RP patients. CONCLUSION: MRI is a valuable staging procedure for prostate
      cancer patients treated by SI. PSA FFP results appear to be improved by MRI
      staging. MRI T(3) disease can be treated more effectively by SI + EBRT than by
      RP.

PMID- 11958884
TI  - Accelerated superfractionated radiotherapy with concomitant boost for locally
      advanced head-and-neck squamous cell carcinomas.
AB  - PURPOSE: A growing body of evidence supports the efficacy of accelerated
      superfractionated radiotherapy with concomitant boost for advanced head-and-neck
      carcinomas. This study represents a single-institution experience, performed to
      identify the factors influencing tumor control, survival, and toxicity. MATERIALS
      AND METHODS: Between 1988 and 1999, 133 patients with primary squamous cell head
      and-neck carcinoma underwent accelerated superfractionated radiotherapy using a
      concomitant boost. The concomitant boost in this regimen was delivered using
      reduced fields delivered 3 times weekly in a twice-daily schedule during the
      final phase. The total radiation dose ranged from 64.8 Gy to 76.5 Gy (mean 71.1).
      Patients were evaluated in follow-up for local control and late toxicity.
      Multivariate analysis of treatment and patient parameters was performed to
      evaluate their influence on toxicity, local control, and overall survival.
      RESULTS: With a mean follow-up of 37 months, the actuarial overall survival rate
      for the entire group at 5 years was 24% and the local control rate was 57%. The
      tumor volume was the most significant predictor of local control, such that each
      1-cm(3) increase in volume was associated with a 1% decrease in local control.
      For patients with tumor volumes </=30 cm(3) vs. >30 cm(3), the 5-year disease
      specific survival rate was 52% and 27% (p = 0.004) and locoregional control rate
      was 76% and 26% (p <0.001), respectively. Seventy-six patients with a minimum of
      12 months and median of 39 months toxicity follow-up were studied for late
      effects. None of these patients experienced Grade 4 or 5 toxicity. The actuarial
      rate of significant toxicity (Grade III or greater) was 32% at 5 years. Of the
      toxicities observed, xerostomia (19%) was the most common. Multivariate analysis
      revealed N stage and dose as independent predictors of Grade 3 effects.
      CONCLUSION: The locoregional control and survival for patients in this
      institutional experience compare favorably to other published reports. Tumors of
      the larynx had the best prognosis. Larger volume tumors were associated with
      significantly lower local control and survival. Significant late effects were
      related to dose and nodal status.

PMID- 11958885
TI  - Effect of treatment delay on outcome of patients with early-stage head-and-neck
      carcinoma receiving radical radiotherapy.
AB  - PURPOSE: Access to radiotherapy (RT) has been considerably reduced in Quebec
      since the late 1980s. The aim of the present study was to analyze the impact of
      delaying treatment on the outcome of patients with early head-and-neck squamous
      cell carcinomas. MATERIALS AND METHODS: This retrospective analysis examined the
      outcome for all 623 patients with early-stage disease (T1-2, N0-1) who received
      radical RT between 1988 and 1997 at the Hotel Dieu of Quebec Hospital. Delay was
      defined as the time from initial evaluation by a radiation oncologist to the
      beginning of RT. Delay intervals were divided as follows: <30 days, 31-40 days,
      and >40 days. RESULTS: A delay of >40 days was significantly associated with an
      increased risk of local and neck failure and poorer survival relative to patients
      treated in <30 days or between 31 and 40 days. The adjusted hazard ratio and (in
      parentheses) the 95% confidence interval was 2.6 (1.07-6.4), 2.73 (1.38-5.4), and
      1.7 (1.1-2.6), respectively, for local failure, neck failure, and survival. In
      the subgroup of patients with T2N0 disease, delaying RT for >30 days was
      associated with a poor outcome, as measured by the same end points. CONCLUSION:
      Delaying RT had a deleterious effect on these patients. RT should be started as
      soon as possible in patients with squamous cell carcinoma of the head and neck,
      preferably within 20-30 days after evaluation by a radiation oncologist.

PMID- 11958886
TI  - Subcutaneous fibrosis after whole neck irradiation.
AB  - PURPOSE: To identify the risk factors for moderate to severe subcutaneous
      fibrosis after whole neck irradiation. MATERIALS AND METHODS: We analyzed 233
      cases of patients who had undergone whole neck irradiation with 4-MV X-ray or 8
      10-MeV electrons, or both, and had been followed with regard to their skin
      condition for at least 1 year. The prescribed dose to the whole neck ranged from
      19.2 to 72.4 Gy (median 50). The skin-absorbed dose was specified as that at a
      depth of 4.1 mm (d4.1-mm(depth)), and a biologically equivalent dose (BED) of
      d4.1-mm(depth) was also estimated (BED(1.8) 4.1-mm(depth)). RESULTS: Univariate
      analysis revealed that previous neck dissection, concurrent chemotherapy,
      corticosteroid administration as a part of chemotherapy, fractionation, and
      BED(1.8) 4.1-mm(depth) were significant prognostic variables. Multivariate
      analysis showed that BED(1.8) 4.1-mm(depth) and previous neck dissection were the
      only prognostic variables for moderate to severe subcutaneous fibrosis.
      CONCLUSION: A high dose to a 4.1-mm depth of the skin and a history of neck
      dissection were identified as the predominant risk factors for moderate to severe
      subcutaneous fibrosis after whole neck irradiation. A subcutaneous dose should be
      considered in radiotherapy treatment planning involving the whole neck,
      especially in cases in which patients have undergone previous neck dissection.

PMID- 11958887
TI  - Side effects and quality of life after inadvertent radiation overdosage in
      brachytherapy of head-and-neck cancer.
AB  - PURPOSE: By comparing our old (DP5, in use from 1978 to 1994) and new (Plato,
      Nucletron) dose planning system, we found that the old system underestimated
      doses by 20-25%. To study the possible consequences for the patients treated
      between 1978 and 1994, all who were still alive were invited to undergo an
      examination with respect to side effects and quality of life (QOL). MATERIALS AND
      METHODS: The degree of overdosage was calculated by comparing the isodose
      distribution generated on the two dose planning systems. Eighty-four patients
      were then invited to undergo an examination with respect to side effects and QOL.
      The side effects were scored according to the LENT SOMA system and QOL according
      to European Organization for Research and Treatment of Cancer (EORTC) Quality of
      Life Questionnaire-Core 30 (QLQ-C30), and EORTC Quality of Life Questionnaire
      Head & Neck 35 (QLQ-H&N35). RESULTS: The mean overdosage of brachytherapy was
      19.3%. No association was found between overdosage and side effects or QOL. For
      implants in the lateral border of the tongue, we found a statistically
      significant correlation between osteoradionecrosis and the following parameters:
      linear activity, total activity, dose rate, and extrapolated response dose. By
      multivariate analysis, only total implanted activity and the use of lead
      protection during brachytherapy were found to be of prognostic significance with
      respect to development of osteoradionecrosis. CONCLUSION: The incidence of side
      effects after brachytherapy at the Norwegian Radium Hospital seems to have been
      somewhat higher in the period under investigation than at other institutions.
      There may be several explanations, including the use of external beam
      radiotherapy before brachytherapy and departure from the Paris system among
      others. However, the side effects were not associated with the overdosage that
      was the basis for the study. As opposed to the general consensus of opinion, long
      term QOL was found to be worse after brachytherapy than after external beam
      radiotherapy. This calls for increased awareness and a systematic prospective
      registration of the long-term side effects of brachytherapy.

PMID- 11958888
TI  - Recurrent head-and-neck chemodectomas: a comparison of surgical and
      radiotherapeutic results.
AB  - PURPOSE: To compare the outcome of salvage radiotherapy (RT) and surgery for
      recurrent head-and-neck chemodectomas. MATERIALS AND METHODS: We retrospectively
      studied 70 patients with benign chemodectomas of the head and neck treated with
      surgery at the Cleveland Clinic between July 1969 and August 1999; 29 of these
      patients were diagnosed with recurrent tumors. Salvage RT was used in 12 patients
      (gamma knife radiosurgery for 7, conventional external beam RT for 4, and
      intensity-modulated RT for 1 patient). The median follow-up was 55 months for the
      entire group of 70 patients. RESULTS: The median time to recurrence was 36
      months. Of the recurrences, 16 were glomus jugulare, 7 were carotid body tumors,
      5 were glomus tympanicum, and 1 was thyroid paraganglioma. RT was used in 12
      patients (9 patients with glomus jugulare, 2 with glomus tympanicum, and 1 with
      thyroid paraganglioma). Surgery was performed in 17 patients (7 patients with
      glomus jugulare, 7 with carotid body, and 3 with glomus tympanicum). For patients
      with glomus jugulare and glomus tympanicum tumors, the 5-year freedom from
      disease progression was 100% for patients treated with RT vs. 62% for those
      treated with surgery (p = 0.0124). Seven patients with carotid body tumors and 1
      patient with thyroid paraganglioma were treated successfully with surgery and RT,
      respectively. No significant side effects were associated with RT; however,
      postoperative complications occurred in 8 of the 17 surgery patients (new cranial
      nerve palsies, meningitis, infection, and cerebrospinal fluid leak). CONCLUSION:
      Salvage RT appears superior to surgery and should be considered the treatment of
      choice for patients with recurrent glomus jugulare and glomus tympanicum tumors.
      For recurrent carotid body tumors, surgery produced excellent local control, most
      likely because of the easier resectability in this location.

PMID- 11958889
TI  - Prognostic influence of parapharyngeal space involvement in nasopharyngeal
      carcinoma.
AB  - PURPOSE: To assess the prognostic influence of parapharyngeal space involvement
      in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From January 1987 to
      December 1994, 197 untreated NPC patients were examined by CT scan before
      treatment. The parapharyngeal space was separated into pre-styloid and post
      styloid compartments on axial images by the styloid process. Potentially
      significant parameters were analyzed by both univariate and multivariate methods
      using SPSS 8.0 software. RESULTS: The actual survival, disease-free survival, and
      local failure-free rates were affected by the presence of parapharyngeal space
      involvement (p = 0.0115, p = 0.0035, p = 0.0367, respectively). The 5-year actual
      survival, disease-free survival, and the local failure-free rates in the patients
      without parapharyngeal space disease, or with pre-styloid and post-styloid
      compartment involvement were 87.9%, 88.0%, 96.9% and 75.0%, 71.2%, 93.7% and
      60.5%, 57.7%, 86.8%, respectively. Parapharyngeal space involvement correlated
      well with lymphadenopathy and advanced N disease. Distant metastasis is more
      likely in the presence of obvious post-styloid compartment involvement (p =
      0.0153). Age is a strong prognostic factor for survival. CONCLUSION:
      Parapharyngeal tumor involvement has significant predictive value. The
      parapharyngeal space involvement affects local tumor failure, regional tumor
      failure, and distant metastasis. Its survival rate is low

PMID- 11958890
TI  - Adjuvant irradiation for axillary metastases from malignant melanoma.
AB  - PURPOSE: To evaluate the outcome and treatment-related toxicity for patients with
      axillary lymph node metastases from malignant melanoma treated with surgery and
      radiation, with or without systemic therapy. MATERIALS AND METHODS: The medical
      records of 89 consecutive patients with axillary lymph node metastases from
      malignant melanoma were retrospectively reviewed. All patients underwent axillary
      dissection and postoperative radiation to a median dose of 30 Gy at 6 Gy/fraction
      delivered twice weekly. In 3 patients referred with microscopic residual disease,
      a single boost (4-6 Gy) was given to a reduced field. All but 2 patients were
      referred because their axillary dissections revealed features believed to predict
      a 30-50% risk of subsequent axillary recurrence: lymph nodes >/=3 cm in size (54
      patients), >/=4 lymph nodes positive (44), the presence of extracapsular
      extension (69), recurrent disease after initial surgical resection (23), or
      multiple risk factors (77). Fifty-one patients received systemic therapy before
      or after radiation therapy. RESULTS: At a median follow-up of 63 months, 47
      patients had relapsed and 43 patients had died. The actuarial overall and disease
      free survival rates at 5 years were 50% and 46%, respectively. The actuarial
      axillary control and distant metastasis-free survival rates at 5 years were 87%
      and 49%, respectively. Univariate analysis revealed that the probability of
      axillary control was inferior when the axillary disease measured >6 cm in size
      (72% vs. 93%, p = 0.02), the location of the primary tumor was unknown (74% vs.
      93%, p = 0.02), the axillary failure occurred within 18 months from diagnosis of
      the primary melanoma (84% vs. 100%, p = 0.04), or the Breslow thickness was >4 mm
      (80% vs. 96%, p = 0.04). Additionally, there was an inferior distant metastasis
      free and disease-free survival when there were >2 nodes positive for metastatic
      disease, the primary lesion had a Breslow thickness >4 mm, or the axillary
      failure occurred within 18 months from diagnosis of the primary melanoma. On
      multivariate analysis, the significantly inferior distant metastasis-free and
      disease-free survival seen when >2 nodes were positive or the recurrence occurred
      within 18 months remained significant. The small number of axillary failures
      precluded multivariate analysis for axillary control; however, stratified
      analysis suggested that size >6 cm was the factor most closely associated with
      subsequent axillary failure. Twenty-six patients developed treatment-related arm
      edema. Classification according to the severity of edema yielded 5-year actuarial
      arm edema rates of 21%, 19%, and 1%, for Grade 1 (transient or asymptomatic),
      Grade 2 (requiring medical intervention), or Grade 3 (requiring surgical
      intervention) edema, respectively. CONCLUSION: Adjuvant radiation therapy using a
      hypofractionated regimen resulted in an 87% 5-year axillary control rate,
      superior to the 50-70% local control achieved with surgery alone for lymph node
      metastases from melanoma when high-risk features are present. Improvements are
      needed for patients with bulky nodal masses >6 cm in size. Mild-to-moderate arm
      edema was common, but manageable. The degree to which radiotherapy adds to the
      risk of arm edema after axillary dissection alone cannot be addressed in the
      present analysis.

PMID- 11958891
TI  - Radiotherapy management for squamous cell carcinoma of the nasal skin: the
      Princess Margaret Hospital experience.
AB  - PURPOSE: To evaluate the outcome of radiotherapy (RT) for squamous cell carcinoma
      (SCC) of the nasal skin. MATERIALS AND METHODS: The charts of 100 patients
      referred and treated with RT during 1982 to 1993 for SCC of nasal skin were
      reviewed. Most patients (81%) were treated with orthovoltage X-rays. In general,
      lesions </=2 cm were treated to 35 Gy in 5 fractions. For tumors 2-5 cm, 45 Gy in
      10 fractions was commonly used. Lesions >5 cm or those associated with bone or
      cartilage invasion were typically treated to 50 Gy in 20 fractions. Six patients
      were lost to follow-up, leaving 94 patients assessable for local or regional
      failure analysis. Using the UICC staging system, the T stage at first
      presentation was as follows: T1, 60 patients; T2, 11 patients; T3, 0 patients,
      T4, 7 patients; TX, 16 patients. Only 1 patient had regional lymph node disease
      at presentation. Thirty-one patients were treated with surgery, followed by RT.
      Sixty-three patients were treated with primary RT. RESULTS: The local relapse
      free rate was 90% and 85% at 2 and 5 years, respectively. The actuarial 2 and 5
      year overall survival rate was 75% and 51%, respectively. The cause-specific
      survival was 96% at both 2 and 5 years. No Radiation Therapy Oncology Group Grade
      4 toxicities occurred. Univariate analysis could not identify any patient, tumor,
      or treatment factors that were statistically significant prognosticators.
      CONCLUSION: RT for SCC of nasal skin achieves excellent outcome, is well
      tolerated, and should continue to be recommended in the management of this
      disease.

PMID- 11958893
TI  - Posttreatment visual acuity in patients treated with episcleral plaque therapy
      for choroidal melanomas: dose and dose rate effects.
AB  - PURPOSE: To determine the relationship between the long-term visual function and
      the dose and dose rates delivered to critical ocular structures in patients with
      choroidal melanoma treated with 125I episcleral plaque radiotherapy. MATERIALS
      AND METHODS: From 1987 to 1994, 63 patients underwent 125I episcleral plaque
      (Collaborative Ocular Melanoma Study [COMS] design) application for the treatment
      of choroidal melanoma. The mean tumor height was 4.5 mm (range 1.7-8.3). Doses
      and dose rates at the tumor apex, macula, and optic disc were calculated. Forty
      three records were scored to assess whether a decrease in visual acuity of >2
      lines on a standard Snellen eye chart had occurred. Patient age and the presence
      of hypertension or diabetes were noted. Statistical analysis was performed to
      assess both the rate at which visual decline had occurred and the presence of
      significant factors that had contributed to this decline. RESULTS: With a median
      follow-up of 36 months, the 3-year actuarial survival rate was 93.6%. The 3-year
      actuarial local control rate was 86.9%. The median time to visual loss after
      therapy was 18.7 months. The 3-year actuarial rate of visual preservation was
      40.5%. Multivariate analysis demonstrated higher macula dose rates (p = 0.003) to
      forecast visual decline. Macula dose rates of 111 +/- 11.1 cGy/h were associated
      with a 50% risk of significant visual loss. CONCLUSION: Patients in our series
      treated with 125I plaque brachytherapy for choroidal melanoma experienced
      favorable tumor control, but with a measurable incidence of visual decline.
      Higher dose rates to the macula correlated strongly with poorer posttreatment
      visual outcome. This information may be valuable in selecting the optimal dose
      rates to treat choroidal melanomas and to predict the risk of visual decline.

PMID- 11958892
TI  - Locoregional failure of postmastectomy patients with 1-3 positive axillary lymph
      nodes without adjuvant radiotherapy.
AB  - PURPOSE: To analyze the incidence and risk factors for locoregional recurrence
      (LRR) in patients with breast cancer who had T1 or T2 primary tumor and 1-3
      histologically involved axillary lymph nodes treated with modified radical
      mastectomy without adjuvant radiotherapy (RT). MATERIALS AND METHODS: Between
      April 1991 and December 1998, 125 patients with invasive breast cancer were
      treated with modified radical mastectomy and were found to have 1-3 positive
      axillary nodes. The median number of nodes examined was 17 (range 7-33). Of the
      125 patients, 110, who had no adjuvant RT and had a minimum follow-up of 25
      months, were included in this study. Sixty-nine patients received adjuvant
      chemotherapy and 84 received adjuvant hormonal therapy with tamoxifen. Patient
      related characteristics (age, menopausal status, medial/lateral quadrant of tumor
      location, T stage, tumor size, estrogen/progesterone receptor protein status,
      nuclear grade, extracapsular extension, lymphovascular invasion, and number of
      involved axillary nodes) and treatment-related factors (chemotherapy and hormonal
      therapy) were analyzed for their impact on LRR. The median follow-up was 54
      months. RESULTS: Of 110 patients without RT, 17 had LRR during follow-up. The 4
      year LRR rate was 16.1% (95% confidence interval [CI] 9.1-23.1%). All but one LRR
      were isolated LRR without preceding or simultaneous distant metastasis. According
      to univariate analysis, age <40 years (p = 0.006), T2 classification (p = 0.04),
      tumor size >==3 cm (p = 0.002), negative estrogen receptor protein status (p =
      0.02), presence of lymphovascular invasion (p = 0.02), and no tamoxifen therapy
      (p = 0.0006) were associated with a significantly higher rate of LRR. Tumor size
      (p = 0.006) was the only risk factor for LRR with statistical significance in the
      multivariate analysis. On the basis of the 4 patient-related factors (age <40
      years, tumor >==3 cm, negative estrogen receptor protein, and lymphovascular
      invasion), the high-risk group (with 3 or 4 factors) had a 4-year LRR rate of
      66.7% (95% CI 42.8-90.5%) compared with 7.8% (95% CI 2.2-13.3%) for the low-risk
      group (with 0-2 factors; p = 0.0001). For the 110 patients who received no
      adjuvant RT, LRR was associated with a 4-year distant metastasis rate of 49.0% (9
      of 17, 95% CI 24.6-73.4%). For patients without LRR, it was 13.3% (15 of 93, 95%
      CI 6.3-20.3%; p = 0.0001). The 4-year survival rate for patients with and without
      LRR was 75.1% (95% CI 53.8-96.4%) and 88.7% (95% CI 82.1-95.4%; p = 0.049),
      respectively. LRR was independently associated with a higher risk of distant
      metastasis and worse survival in multivariate analysis. CONCLUSION: LRR after
      mastectomy is not only a substantial clinical problem, but has a significant
      impact on the outcome of patients with T1 or T2 primary tumor and 1-3 positive
      axillary nodes. Patients with risk factors for LRR may need adjuvant RT.
      Randomized trials are warranted to determine the potential benefit of
      postmastectomy RT on the survival of patients with a T1 or T2 primary tumor and 1
      3 positive nodes.

PMID- 11958894
TI  - Ki-67: a prognostic factor for low-grade glioma?
AB  - PURPOSE: Immunohistochemical techniques were used to detect the expression of Ki
      67, a nuclear proliferation marker, in 180 low-grade glioma tumor specimens to
      determine whether Ki-67 is a prognostic predictor of survival or tumor
      recurrence. MATERIALS AND METHODS: A clinical database of 180 low-grade glioma
      patients (35 children aged </=18 years and 145 adults) was compiled. Eighty
      patients had received postoperative radiotherapy (RT) and 100 patients had had RT
      deferred until the time of tumor progression/recurrence. Ki-67 indexes were
      evaluated retrospectively on tumor specimens from these patients using a
      semiautomated computer analysis technique. Ten observations were averaged per
      patient. The maximal Ki-67 value was recorded. RESULTS: The correlation between
      the Ki-67 index and survival was much higher for the averaged Ki-67 value than
      for the maximal value. Of the tumor specimens, 29% had a negative Ki-67 index
      (i.e., zero Ki-67 positive cells) and 7.7% had an average Ki-67 index of >/=5%.
      An average Ki-67 value of >/=5% was prognostically significant for reduced cause
      specific survival (CSS, p = 0.05) and a Ki-67 level >/=10% was strongly
      significant of a poor survival outcome (p = 0.009). Ki-67 was not prognostically
      significant for progression-free survival. Other prognostically significant
      factors for CSS included age (p = 0.05), Karnofsky performance status (p =
      0.0001), radiation dose (p = 0.02), extent of surgical resection (biopsy vs.
      others, p = 0.004), and timing of radiation (p = 0.0005). Ki-67 did not remain an
      independent statistically significant factor for CSS on multivariate analysis.
      Age and Ki-67 positivity (both maximal and average values) directly correlated
      (i.e., advancing age was associated with a higher Ki-67 index). When the patient
      group was further subdivided by age and timing of RT (postoperative vs.
      deferred), the prognostic significance of Ki-67 for CSS was lost. Within the
      deferred RT subgroup, a maximal Ki-67 >2% was associated with a worsened CSS.
      Within the pediatric population, Ki-67-negative patients had a 5-year CSS and
      progression-free survival of 100%. The 5-year CSS and progression-free survival
      declined significantly to 84% and 67% for patients with tumors demonstrating any
      degree of Ki-67 positivity (p = 0.005 and p = 0.006, respectively). CONCLUSION:
      Ki-67 is a useful predictor of CSS in low-grade gliomas; however, it is not
      independent of other prognostic factors, particularly age. Although Ki-67 was not
      helpful in predicting which adult patients were likely to benefit from
      postoperative RT, the results of the present study indicate a possible utility in
      the selection of pediatric patients for RT and in the selection of poorer
      prognosis patients for clinical trials.

PMID- 11958895
TI  - Stereotactic radiosurgery: the preferred management for patients with
      nonvestibular schwannomas?
AB  - PURPOSE: To review patient outcomes after radiosurgery of nonvestibular
      schwannomas. MATERIALS AND METHODS: From April 1992 to February 2000, 23 patients
      had radiosurgery at our center for nonvestibular schwannomas. Affected cranial
      nerves included the trochlear (n = 1), trigeminal (n = 10), jugular foramen
      region (n = 10), and hypoglossal (n = 2). Nine patients had undergone one or more
      prior tumor resections. One patient had a malignant schwannoma; 2 patients had
      neurofibromatosis. The median prescription isodose volume was 8.9 cc (range, 0.2
      to 17.6 cc). The median tumor margin dose was 18 Gy (range, 12 to 20 Gy); the
      median maximum dose was 36 Gy (range, 24 to 40 Gy). The median follow-up after
      radiosurgery was 43 months (range, 12 to 111 months). RESULTS: Twenty-two of 23
      tumors (96%) were either smaller (n = 12) or unchanged in size (n = 10) after
      radiosurgery. One patient with a malignant schwannoma had tumor progression
      outside the irradiated volume despite having both radiosurgery and fractionated
      radiation therapy (50.4 Gy); he died 4 years later. Morbidity related to
      radiosurgery occurred in 4 patients (17%). Three of 10 patients with trigeminal
      schwannomas suffered new or worsened trigeminal dysfunction after radiosurgery.
      One patient with a hypoglossal schwannoma had eustachian tube dysfunction after
      radiosurgery. No patient with a lower cranial nerve schwannoma developed any
      hearing loss, facial weakness, or swallowing difficulty after radiosurgery.
      CONCLUSIONS: Although the reported number of patients having radiosurgery for
      nonvestibular schwannomas is limited, the high tumor control rates demonstrated
      after vestibular schwannoma radiosurgery should apply to these rare tumors.
      Compared to historical controls treated with surgical resection, radiosurgery
      appears to have less treatment-associated morbidity for nonvestibular
      schwannomas, especially for schwannomas involving the lower cranial nerves.

PMID- 11958896
TI  - Acute toxicity and treatment interruption related to electron and photon
      craniospinal irradiation in pediatric patients treated at the University of Texas
      M. D. Anderson Cancer Center.
AB  - PURPOSE: To determine the incidence of acute toxicity and treatment interruption
      associated with electron and photon craniospinal irradiation (CSI) in children
      treated with or without chemotherapy. MATERIALS AND METHODS: A retrospective
      study involving a computerized search of the radiotherapy database at the
      University of Texas M. D. Anderson Cancer Center identified a total of 79
      eligible patients </=18 years old who had received electron (n = 46) or photon (n
      = 33) CSI from October 1980 to March 2000. Acute toxicity was graded according to
      the 1998 National Cancer Institute Common Toxicity Criteria. Chemotherapy
      sequencing was categorized as before or after CSI or no chemotherapy. The
      incidences of weight loss and skin toxicity were recorded and differences in
      treatment interruption and hematologic values with respect to modality used
      (electron vs. photon), age (</=6 or >6 years), and sequencing of chemotherapy
      were compared using chi-square tests. RESULTS: The median age of the electron
      group was lower than that of the photon group (6.7 years and 11.7 years,
      respectively). The two groups were otherwise well matched in terms of median
      spinal dose (31.1 vs. 33.3 Gy), fraction size (1.57 vs. 1.63 Gy), and total
      treatment time (32.4 vs. 30.7 days). Only 2 patients in each group (photon and
      electron) had a treatment break (>3 days). The mean number of days interrupted
      was 0.94 (photon) and 1.1 (electron) (p = 0.72). The electron and photon groups
      were well balanced in terms of receiving pre-CSI chemotherapy (37% vs. 41%, p =
      0.776). Chemotherapy given before radiotherapy vs. after or not at all was
      associated with an increased incidence of Grade 3-4 leukopenia (76% vs. 49%, p =
      0.02), thrombocytopenia (90% vs. 10%, p = 0), and neutropenia (50% vs. 15%, p =
      0.005). A younger age was associated with Grade 3-4 thrombocytopenia (29% vs.
      8.7%, p = 0.034), and decreased hemoglobin (29% vs. 6.5%, p = 0.014). The
      incidence of leukocyte depression of Grade 3-4 toxicity was 62% in the electron
      group and 32% in the photon group (p = 0.018). The incidence of Grade 3-4
      platelet toxicity was higher with electrons (21%) than with photons (4%), but the
      difference was of borderline significance (p = 0.053). The difference in Grade 1
      2 weight loss was not statistically significant (86% electron vs. 55% photon
      groups, p = 0.53), and Grade 3-4 weight loss did not occur within the entire
      study group. Most patients experienced Grade 0-1 radiation dermatitis with either
      electrons or photons. CONCLUSION: A younger patient age (</=6 years) and the
      sequence of chemotherapy before radiotherapy were associated with increased acute
      hematologic toxicity. Grade 3-4 weight loss, a surrogate for gastrointestinal
      toxicity, was not observed within the entire population. Despite the increased
      acute hematologic toxicities associated with CSI in very young children, the vast
      majority of patients were able to complete photon or electron CSI with minimal to
      no treatment interruptions. CSI with the electron technique can be used as an
      alternative to photon CSI in young children, and in our experience does not
      require the routine use of hematopoietic growth factors.

PMID- 11958897
TI  - Proton radiotherapy in management of pediatric base of skull tumors.
AB  - PURPOSE: Primary skull base tumors of the developing child are rare and present a
      formidable challenge to both surgeons and radiation oncologists. Gross total
      resection with negative margins is rarely achieved, and the risks of functional,
      structural, and cosmetic deficits limit the radiation dose using conventional
      radiation techniques. Twenty-nine children and adolescents treated with conformal
      proton radiotherapy (proton RT) were analyzed to assess treatment efficacy and
      safety. MATERIALS AND METHODS: Between July 1992 and April 1999, 29 patients with
      mesenchymal tumors underwent fractionated proton (13 patients) or fractionated
      combined proton and photon (16 patients) irradiation. The age at treatment ranged
      from 1 to 19 years (median 12); 14 patients were male and 15 female. Tumors were
      grouped as malignant or benign. Twenty patients had malignant histologic
      findings, including chordoma (n = 10), chondrosarcoma (n = 3), rhabdomyosarcoma
      (n = 4), and other sarcomas (n = 3). Target doses ranged between 50.4 and 78.6
      Gy/cobalt Gray equivalent (CGE), delivered at doses of 1.8-2.0 Gy/CGE per
      fraction. The benign histologic findings included giant cell tumors (n = 6),
      angiofibromas (n = 2), and chondroblastoma (n = 1). RT doses for this group
      ranged from 45.0 to 71.8 Gy/CGE. Despite maximal surgical resection, 28 (97%) of
      29 patients had gross disease at the time of proton RT. Follow-up after proton RT
      ranged from 13 to 92 months (mean 40). RESULTS: Of the 20 patients with malignant
      tumors, 5 (25%) had local failure; 1 patient had failure in the surgical access
      route and 3 patients developed distant metastases. Seven patients had died of
      progressive disease at the time of analysis. Local tumor control was maintained
      in 6 (60%) of 10 patients with chordoma, 3 (100%) of 3 with chondrosarcoma, 4
      (100%) of 4 with rhabdomyosarcoma, and 2 (66%) of 3 with other sarcomas. The
      actuarial 5-year local control and overall survival rate was 72% and 56%,
      respectively, and the overall survival of the males was significantly superior to
      that of the female patients (p = 0.002). Of the patients with benign tumors, 1
      patient (giant cell tumor) had local failure at 10 months. The other 8 patients
      continued to have local tumor control; all 9 patients were alive at last follow
      up (actuarial 5-year local control and overall survival rate of 89% and 100%,
      respectively). Severe late effects (motor weakness and sensory deficits) were
      observed in 2 (7%) of 29 patients. CONCLUSION: Proton RT for children with
      aggressively recurring tumors after major skull base surgery can offer a
      considerable prospect of tumor control and survival. Longer follow-up is
      necessary to assess the real value of protons, in particular with regard to bone
      growth and cosmetic outcome.

PMID- 11958898
TI  - Locoregional control in infants with neuroblastoma: role of radiation therapy and
      late toxicity.
AB  - PURPOSE: To review patterns of failure in infants with neuroblastoma and
      determine late toxicity and efficacy of radiotherapy (RT) on locoregional
      control. MATERIALS AND METHODS: From 1955 to 1998, 53 children (35 males and 18
      females) <1 year old with neuroblastoma were seen at our institution. Twenty-one
      (40%) were </=1 month of age (neonates). Seven congenital anomalies were seen in
      4 children (atrial septal defect, pulmonary valve stenosis, and absent corpus
      callosum were seen in 1 patient each; the other child had atrial and ventricular
      septal defect, aortic arch hypoplasia, and mitral valve stenosis). Primary tumor
      was located in the adrenal gland in 26 (49%), abdomen/nonadrenal in 14 (26%),
      thorax in 9 (17%), neck in 2 (4%), and pelvis in 2 (4%). All infants were
      retrospectively staged according to the International Neuroblastoma Staging
      System (INSS); 8 had Stage 1, 7 Stage 2A, 6 Stage 2B, 15 Stage 3, 6 Stage 4, and
      11 Stage 4S. All patients, except 11 with Stage 4S and 4 with Stage 4, had
      resection of the primary tumor. Sixteen infants had pathologic involvement of
      regional lymph nodes (LN+). Twenty patients received RT. Kilovoltage beams were
      used in 10, megavoltage photons in 9, and electrons in 1 child. Fifteen received
      RT to the primary site and regional nodes (postoperative 8, preoperative 7).
      Postoperative doses ranged from 15 to 25 Gy whereas preoperative doses ranged
      from 12 to 31 Gy using a median fraction size of 1.5 Gy. Chemotherapy was
      employed in 22 of 53 patients (42%) with the most common agents being
      cyclophosphamide in 22 and doxorubicin in 11. Median follow-up was 13.1 years
      (range, 2-41 years). RESULTS: Tumor control: The 5-year overall and freedom from
      progression rates were 79 +/- 9% and 81 +/- 11%; the locoregional control rate
      was 88 +/- 9%. INSS Stage was a prognostic factor for overall survival (p = 0.03)
      and freedom from progression (p = 0.035). Gender, age (</=1 month vs. >1 month),
      and primary site were not found to impact on survival or progression. None of the
      Stage 1, 2A, or 2B patients recurred. One of 15 Stage 3 and 5 of 6 Stage 4
      children recurred (6 distant metastases, 4 local failure). Four of 6 (67%) LN+
      patients treated with locoregional RT and 8 of 10 (80%) LN+ patients treated
      without RT were locally controlled. There was no isolated locoregional relapse.
      Two Stage 4S patients died of respiratory compromise secondary to hepatomegaly.
      RT toxicity: For the 20 infants who received RT, 13 are alive with long-term
      follow-up ranging from 9.3 to 41 years, median 23 years. The 10 and 15-year
      musculoskeletal toxicity rates were 38.5% and 47.3% for those receiving RT and
      3.3% for no RT (p = 0.02, log-rank test). Five of 6 infants <6 months of age and
      1 of 7 >/=6 months developed musculoskeletal toxicity. Musculoskeletal effects
      were seen in 6 RT patients and included bony hypoplasia in 6, scoliosis in 5,
      soft tissue hypoplasia in 3, slipped capital femoral epiphysis in 2, kyphosis in
      1, and osteochondroma in 1. Three required orthopedic intervention, all receiving
      >/=20 Gy. One child developed bowel obstruction at 21 months and another
      developed a leiomyosarcoma in the treatment field 34 years after RT. CONCLUSION:
      Our study shows that most LN+ infants achieve locoregional control without RT.
      Infants <6 months receiving RT were the most susceptible to musculoskeletal
      abnormalities. Further studies are needed to determine if cardiovascular
      anomalies are more frequently seen in children with neuroblastoma.

PMID- 11958899
TI  - Angiosarcoma treated with radiotherapy: impact of tumor type and size on outcome.
AB  - PURPOSE: Angiosarcoma is a rare and highly malignant vascular neoplasm. The
      purpose of this study was to elucidate the tumor characteristics and evaluate the
      efficacy of radiotherapy (RT) for angiosarcoma. MATERIALS AND METHODS: Thirty
      patients with angiosarcoma (20 males and 10 females, age range 4-89 years, median
      66) who received RT from 1986 to 1999 were enrolled in the study. Twenty-four
      patients had angiosarcoma of the face and scalp (AFS), and 6 patients had
      angiosarcomas at other sites. AFS was classified into two categories (according
      to the macroscopic features): nodular AFS (14 patients) and endophytic AFS (10
      patients). The median prescribed irradiation dose was 68 Gy. Surgery had been
      previously performed in 9 patients, and adjuvant immunotherapy using recombinant
      interleukin-2 (rIL-2) was combined during and after RT in 20 patients. Univariate
      analyses and calculation of survival by Kaplan-Meier methods were performed.
      RESULTS: Local tumor control was obtained in 17 patients (57%). However, 7 (47%)
      of them developed distant metastases. The median survival time for all patients
      was 8 months (7 months for AFS), and the 13-year overall survival rate was 25%
      (20% for AFS). Twenty-one patients died of angiosarcoma, with the cause of death
      local failure in 7 patients, distant failure in 7, and both in 7. Tumor type and
      size were found to be significant prognostic factors (p = 0.004 and p = 0.007,
      respectively), and age, total amount of rIL-2, gender, radiation dose, and
      surgery were not. Six patients (4 with nodular AFS and 2 with angiosarcoma in
      other parts) survived >2 years. No patient with endophytic AFS survived >2 years.
      Ten patients (33%) died of respiratory failure secondary to pulmonary metastases.
      High-dose rIL-2 administration suppressed the occurrence of distant metastases (p
      = 0.006). Two patients developed radiation dermatitis (Radiation Therapy Oncology
      Group Grade 4). CONCLUSION: RT, combined with complete resection or adjuvant rIL
      2 immunotherapy, could be a promising treatment strategy, leading to prolonged
      survival in patients with angiosarcoma.

PMID- 11958900
TI  - Clinical outcomes of 3D conformal hypofractionated single high-dose radiotherapy
      for one or two lung tumors using a stereotactic body frame.
AB  - PURPOSE: This study was performed to evaluate the clinical outcomes of three
      dimensional (3D) conformal hypofractionated single high-dose radiotherapy for one
      or two lung tumors using a stereotactic body frame. MATERIALS AND METHODS: Forty
      patients who were treated between July 1998 and November 2000 and were followed
      for >10 months were included in this study. Of the 40 patients, 31 had primary
      lung cancer and 9 had metastatic lung cancer. The primary lung cancer was staged
      as T1N0M0, T2N0M0, and T3N0M0 in 19, 8, and 4 patients, respectively. The primary
      sites of metastatic lung cancer were the colon in 4, tongue in 2, and
      osteosarcoma, lung cancer, and hepatocellular carcinoma in 1 each. 3D treatment
      planning was performed to maintain the target dose homogeneity within 15% and to
      decrease the irradiated lung volume from >20 Gy to <25%. All patients were
      irradiated using a stereotactic body frame and received 4 times 10-12 Gy single
      high-dose radiation at the isocenter during a period of 5-13 days (median 12).
      RESULTS: The initial 3 patients received 40, and the remaining 37 patients
      received 48 Gy after dose escalation. Of the 33 tumors followed >6 months, 6
      tumors (18%) disappeared completely after treatment. Twenty-five tumors (76%)
      decreased in size by 30% or more after treatment. Therefore, 31 tumors (94%)
      showed a local response. During the follow-up of 4-37 months (median 19), no
      pulmonary complications greater than National Cancer Institute-Common Toxicity
      Criteria Grade 2 were noted. Of the 16 patients with histologically confirmed
      T1N0M0 primary lung cancer who received 48 Gy, all tumors were locally controlled
      during the follow-up of 6-36 months (median = 19). In 9 tumors with lung
      metastases that were irradiated with 48 Gy in total, 2 tumors did not show a
      local response. Finally, 3 tumors (33%) with lung metastases relapsed locally at
      6-12 months (median 7) after treatment during the follow-up of 3-29 months
      (median 18). CONCLUSION: 3D conformal hypofractionated single high-dose
      radiotherapy of 48 Gy in 4 fractions using a stereotactic body frame was useful
      for the treatment of lung tumors.

PMID- 11958901
TI  - Comorbidity and KPS are independent prognostic factors in stage I non-small-cell
      lung cancer.
AB  - PURPOSE: To determine the prognostic role of comorbidity in Stage I non-small
      cell lung cancer (NSCLC) treated with surgery or radiotherapy (RT). MATERIALS AND
      METHODS: One hundred sixty-three patients with clinical Stage I NSCLC were
      analyzed for overall survival (OS) and comorbidity. One hundred thirteen patients
      underwent surgery (surgical group) and 50 patients received definitive
      radiotherapy (RT group). Ninety-six percent of the surgical group had lobectomy
      or pneumonectomy, and negative margins were achieved in 96% of the patients. The
      median dose to the tumor for the RT group was 61.2 Gy (range 30.8-77.4). The
      Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and the Charlson scale
      were used to rate comorbidity. Karnofsky performance scores (KPS) were available
      in 42 patients; the rest of the scores were determined retrospectively by two
      physicians independently, with 97% agreement. RESULTS: The OS was 44% for the
      surgical group and 5% for the RT group at 5 years. Noncancer-related mortality
      was observed in 31% and 62% of the surgical and RT patients, respectively. On
      univariate analysis, performed on all patients (n = 163), squamous cell
      histologic type (p <0.001), clinical Stage T2 (p = 0.062), tumor size >4 cm (p =
      0.065), >40 pack-year tobacco use (p <0.001), presence of a CIRS-G score of 4
      (extremely severe, CIRS-G4: [+]) (p <0.001), severity index of >2 (p <0.001),
      Charlson score >2 (p = 0.004), KPS <70 (p <0.001), and treatment with RT (p
      <0.001) were associated with a statistically significant inferior OS.
      Multivariate analysis with histologic features, clinical T stage, age, tobacco
      use, KPS, comorbidity [CIRS-G(4)] and treatment group on all patients showed that
      squamous cell histology, >40 pack-year tobacco use, KPS <70, and presence of CIRS
      G(4) were independently associated with an inferior OS. Treatment modality, T
      stage, and age did not have any statistically significant effect on OS.
      Statistically significant differences were found between the surgical and RT
      groups in Charlson score (p = 0.001), CIRS-G total score (p = 0.004), severity
      index (p = 0.006), CIRS-G4(+) (p <0.001), KPS (p <0.001), amount of tobacco use
      (p = 0.002), clinical tumor size (p <0.001), clinical T stage (p = 0.01), forced
      expiratory volume in 1 s (p = 0.001), and age (p = 0.008), in favor of the
      surgical group. CONCLUSION: The presence of significant comorbidity and KPS of
      <70 are both important prognostic factors, but were found to be independent of
      each other in Stage I NSCLC. Therefore, comorbidity and KPS assessment are
      recommended when analyzing the prognostic effects of tumor or treatment-related
      factors on OS.

PMID- 11958902
TI  - Treatment outcome of mucosa-associated lymphoid tissue/marginal zone non
      Hodgkin's lymphoma.
AB  - PURPOSE: To evaluate the treatment outcome in patients with mucosa-associated
      lymphoid tissue (MALT)/marginal zone (MZ) non-Hodgkin's lymphoma (NHL). MATERIALS
      AND METHODS: Between 1986 and 2000, 66 patients with clinical stage (CS) I-IV
      MALT/MZ NHL were treated; these comprise the study population. The progression
      free survival (PFS) and overall survival (OS) were calculated using the Kaplan
      Meier technique. Forty-five patients (68%) had CS I-II and 21 (32%) had CS III-IV
      disease. Twenty-nine of the 45 CS I-II patients received radiation therapy (RT)
      alone, and 6 patients had surgery and RT. The median RT dose was 3350 cGy. Among
      the 21 CS III-IV patients, treatment included chemotherapy alone (15),
      chemotherapy + RT (3), surgery (1), surgery + chemotherapy (1), and RT alone (1).
      Median follow-up was 48 months. RESULTS: All 35 early-stage and all 4 advanced
      stage patients who received RT as part of initial treatment achieved local
      control. Among the 63 evaluable patients, the 5-year OS and PFS were 90 and 57%,
      respectively. The 5-year OS was 93% and PFS was 75% among CS I-II patients; the
      corresponding estimates in CS III-IV patients were 83% and 14%, respectively.
      CONCLUSION: Modest doses of RT provide excellent local control in patients with
      MALT/MZ NHL. The poor PFS in advanced-stage patients suggests the need to develop
      alternative systemic treatment strategies for this disease.

PMID- 11958903
TI  - Long-term outcome in endometrial carcinoma favors a two- instead of a three
      tiered grading system.
AB  - PURPOSE: Endometrial carcinoma is the most common malignancy of the female
      genital tract. Recognized prognostic factors include FIGO stage, histologic
      grade, depth of myometrial invasion, and age. Although determination of these
      factors may seem clear and reproducible, the histologic grade has recently been
      the subject of debate. A retrospective analysis of long-term outcome and
      predictive factors in endometrial carcinoma was conducted, focusing on the
      prognostic value of tumor grade. MATERIALS AND METHODS: The study included 253
      patients with endometrial carcinoma Stages I to III, who were treated between
      1984 and 1993. The histologic slides were reviewed and the prognostic value of
      stage, age, myometrial invasion (depth and pattern), tumor grade, and histologic
      subtype was analyzed. The end point was cancer-specific death; the median follow
      up time was 11.7 years. RESULTS: The actuarial 5- and 10-year cancer-specific
      survival rates (CSS) were 85% and 82%, respectively. Five-year vaginal and/or
      pelvic recurrence and distant relapse rates were 7% and 15%. In multivariate
      analysis, stage, pattern of myometrial invasion, tumor grade, and age were
      independent prognostic factors. At pathology review, a shift from Grade 2 to
      Grade 1 was seen in 112 of the original 144 Grade 2 (78%). There was no
      difference in CSS between Grade 1 and Grade 2 (94 vs. 90% for original grade and
      92 vs. 95% for grade after review), whereas Grade 3 was found to be a significant
      adverse prognostic factor (p < 0.001). CONCLUSIONS: The independent prognostic
      factors for patients with endometrial cancer were stage, pattern of myometrial
      invasion, tumor grade, and age. Systematic grading led to a considerable shift
      from Grade 2 to Grade 1. However, there was no difference in prognostic
      significance between Grade 1 and 2, whereas Grade 3 was a major adverse
      prognostic factor. A two-tiered grading system, instead of the currently used
      three-tiered system seems preferable, because it has a better correlation with
      clinical outcome and is expected to have less interobserver variability.

PMID- 11958904
TI  - Clinical and angiographic outcomes after use of 90Strontium/90Yttrium beta
      radiation for the treatment of in-stent restenosis: results from the Stents and
      Radiation Therapy 40 (START 40) registry.
AB  - PURPOSE: To evaluate the safety and efficacy of a 40-mm 90Strontium/90Yttrium
      source train in the management of in-stent restenosis within native coronary
      arteries. MATERIALS AND METHODS: This multicenter, prospective registry was
      designed to compare the results of patients with in-stent restenosis treated with
      a 40-mm source train to the placebo arm of the previously reported randomized
      Stents and Radiation Trial (START). All patients entered in the registry were
      treated with repeat balloon angioplasty followed by intravascular brachytherapy.
      Radiation dose was prescribed based on vessel size. 18 Gy was delivered at 2 mm
      for vessel diameters between 2.75 and 3.35 mm, and 23 Gy was used for vessels
      between 3.36 and 4.0 mm. The efficacy endpoints for the START 40 registry
      included a reduction in the target lesion revascularization (TLR) rate, target
      vessel revascularization rates, and target vessel failure (TVF) at 8 months.
      Secondary angiographic efficacy endpoints were binary restenosis at 8 months, in
      stent minimum luminal diameter (MLD), and late loss. The safety endpoints
      included major adverse cardiac events as well as late aneurysm formation. The
      registry was designed to allow a statistically valid comparison of these results
      to the placebo group of the START 30 trial. Quantitative angiographic analysis
      was performed on the 8-month follow-up examination. Rates of restenosis were
      evaluated for various segments of the treated vessel. A separate analysis was
      performed to evaluate the relationship between vessel injury length and the
      radiated segment. RESULTS: A total of 207 patients were entered into the START 40
      registry. The postprocedure angiographic results, including the postprocedure MLD
      and percent diameter stenosis, were similar between the START 40 patients and the
      placebo group from the START trial in the stented segment of the treated vessel.
      Eight-month angiographic follow-up was available on 150 patients from the
      registry. The TLR rate was significantly reduced when compared to the placebo
      group (11% vs. 22.4% respectively, p = 0.008). A similar reduction was seen in
      terms of target vessel revascularization (15.9% vs. 24.1%, p = 0.03). The 8-month
      MLD was found to be significantly larger in the START 40 patients (1.85 mm vs.
      1.47 mm, p < 0.0001). The difference seen in the clinical endpoint of TVF (19.3%
      vs. 25.9%) did not reach statistical significance (p = 0.1). Analysis of the
      procedural angiograms revealed mismatch between the length of vessel injured and
      the location of the 90% isodose in 46% of the treated cases. Angiographic
      analysis revealed that geographic miss was associated with a higher rate of
      binary restenosis (32% vs. 18% p = 0.04) in the analysis segment. CONCLUSIONS:
      This multicenter registry demonstrates the safety and efficacy of a 40-mm
      90Strontium/90Yttrium source train in the management of patients with in-stent
      restenosis. Restenosis rates were lowered with the use of this longer source
      train when compared to the placebo arm of the START trial for lesions with a
      maximum vessel injury length of 20 mm. Angiographic analysis identified the
      importance of the accurate delineation of injury length and correct source
      positioning. These results support the continued use of beta radiation for the
      treatment of this disease process.

PMID- 11958906
TI  - Radiosensitization by oxaliplatin in a mouse adenocarcinoma: influence of
      treatment schedule.
AB  - PURPOSE: The aim of our study was to investigate if oxaliplatin (1-OHP) could be
      used as a radiosensitizer in vivo. MATERIALS AND METHODS: Experiments were
      performed in mice (C3D2F1) bearing a transplanted mammary carcinoma in a foot.
      Drugs, 1-OHP and cis-diammine-dichloro-platinum (CDDP), were administered i.p.
      Results were analyzed in terms of tumor growth delay (TGD). RESULTS: 1-OHP and
      CDDP were tested in single doses of 6 and 10 mg/kg body weight. Administration of
      either 1-OHP or CDDP produced a significant TGD but only with the dose of 10
      mg/kg. Single dose combined X-ray (10 Gy) and 1-OHP (6 and 10 mg/kg) treatments
      were performed with different sequences and time intervals (1 h, 4 h, and 24 h).
      All TGDs of these combined treatments were uniform among themselves (indicating
      that sequence and time interval did not influence the results), and did not
      depend on the drug dose. In X-ray (10 and 20 Gy) and 1-OHP (6 and 10 mg/kg)
      combined treatment, the TGDs increased only with X-ray dose. Different 1-OHP
      administration schedules were performed for fractionated experiments: two
      treatments every 4 days. The least toxic protocol (1-OHP total dose from 6 to 14
      mg/kg) was selected for combined treatments with 10 daily X-ray treatments of 2
      Gy. A clear drug dose-effect relationship was observed in those treatments with 1
      OHP doses from 10 to 14 mg/kg. CONCLUSION: Although low-dose 1-OHP did not induce
      a TGD when administered alone, in combined protocols it increased X-ray efficacy.

PMID- 11958905
TI  - Palliative radiation for vertebral metastases: the effect of variation in
      prescription parameters on the dose received at depth.
AB  - PURPOSE: To assess the effect of prescription parameters on the dose received by
      the spine during palliative radiotherapy. MATERIALS AND METHODS: In a survey,
      members of the Canadian Association of Radiation Oncologists were asked to define
      their prescription parameters for vertebral metastases. The depth of the spinal
      canal and vertebral body at 8 spinal levels was measured in 20 magnetic resonance
      imaging studies (MRIs). Survey results were applied to the measurements to assess
      the dose received at depth. The depth of spinal structures assessed at simulation
      and by diagnostic imaging was compared. RESULTS: Prescriptions were most commonly
      to D(max) 3 cm or 5 cm using 60Co-6MV photons delivering 8-30 Gy in 1-10
      fractions. Mean depths from MRI were: posterior spinal canal, 5.5 cm; anterior
      spinal canal, 6.9 cm; and anterior vertebral body, 9.6 cm. Application of the
      prescription parameters from the survey to these measurements showed a wide range
      in the dose at depth with variation in technique. Depths measured at simulation
      correlated well with diagnostic imaging. CONCLUSION: The spinal canal and
      vertebral body lie >5 cm beneath the skin, and the dose received varies by up to
      50% with changes in prescription depth. We suggest a suitable prescription point
      for vertebral metastases and a method for determining this at simulation.

PMID- 11958907
TI  - No benefits of ultrafractionation in two head-and-neck cancer cell lines with
      different inherent radiosensitivity.
AB  - PURPOSE: To assess if ultrafractionation is applicable in the context of an
      unknown hyperradiosensitivity (HRS) status, we studied the survival and repair
      capacity of two tumor cell lines after irradiation with two different
      dose/fractionation schedules that can be used in a clinical setting. MATERIALS
      AND METHODS: Squamous cell carcinoma cell lines SCC-3 (radioresistant) and SCC-6
      (radiosensitive) were used. Survival was studied by clonogenic assay after
      multiple fractions of 0.5 Gy (2 fractions/day, 6-h interval) and 2 Gy (1
      fraction/day) for a total dose of 8 Gy of gamma-rays. The capacity to repair
      single-strand and double-strand breaks (SSB, DSB) was assessed by comet assay.
      The messenger RNA (mRNA) levels of DNA-dependent protein kinase (PK) components
      were analyzed by RNase protection and real-time polymerase chain reaction (PCR).
      RESULTS: In both cell lines, no apparent difference was noted between the two
      fractionation protocols. In particular for SCC-3, the mean surviving fraction
      tended to be lower after 2 Gy than after 0.5 Gy fractions. In SCC-3 and SCC-6 no
      significant difference was observed in the repair capacity of SSB and DSB after
      exposure to single doses of 0.5 Gy or 2 Gy. After exposure to the same single
      doses, the mRNA levels of DNA-PK catalytic subunit (PKcs), Ku 70, and Ku 80 were
      similar. CONCLUSIONS: Our data do not support the concept of ultrafractionation,
      at least when using fractions of 0.5 Gy in the cell lines studied. This suggests
      that methods for testing HRS status in individual tumors need to be developed
      before the relevance of ultrafractionation can be investigated in the clinic.

PMID- 11958908
TI  - PET-guided three-dimensional treatment planning of intracavitary gynecologic
      implants.
AB  - PURPOSE: Positron emission tomography (PET) provides physiologic information that
      is not available from computed tomography (CT) or magnetic resonance studies. PET
      images may allow more accurate delineation of three-dimensional treatment
      planning target volumes of brachytherapy gynecologic (GYN) implants. This study
      evaluates the feasibility of using PET as the sole source of target, normal
      structure, and applicator delineation for intracavitary GYN implant treatment
      planning. MATERIALS AND METHODS: Standard Fletcher-Suit brachytherapy tandem and
      colpostat applicators were used for radiation delivery. After insertion of the
      applicator in the operating room, the patient was taken to a PET scanner, where
      555 MBq (15 mCi) 18F-fluorodeoxyglucose (18F-FDG) was administered intravenously.
      Forty-five minutes later, three localization tubes containing 18F-FDG were
      inserted into the source afterloading compartments of the tandem and colpostat. A
      whole-pelvis scan was performed, and the images were transferred to a commercial
      brachytherapy three-dimensional treatment planning system. A Foley catheter was
      inserted into the urinary bladder while the patient was in the operating room.
      The regions of radioactivity in the three applicator tube image were contoured
      for reconstruction of the applicator, along with the bladder, rectum, and 18F-FDG
      defined target volumes. A treatment plan was generated that included dose-volume
      histograms and three-dimensional dose distribution displays, allowing the
      physician an opportunity to determine if adequate target coverage and normal
      tissue sparing had been obtained. For a more conservative approach, three
      dimensional dose distributions and dose-volume histograms delivered with
      conventional source arrangements and loading could be observed. The accuracy of
      applicator localization from the PET images was verified using a water phantom
      containing two aluminum CT-compatible tandems. The PET-defined and CT scan
      applicator reconstructions were compared. RESULTS: Feasibility of using PET
      images for treatment planning of brachytherapy intracavitary GYN implants has
      been demonstrated. A phantom study demonstrated applicator reconstruction
      accuracy in the axial direction to be better than 2 mm. Reconstruction accuracy
      in the longitudinal direction (principally craniocaudal) was similar to the PET
      scanner's voxel size of 4.3 mm. CONCLUSIONS: Brachytherapy intracavitary GYN
      implant design has traditionally been based on patient tumor staging, palpation,
      and clinical experience. PET images have the potential to provide better spatial
      information about the relationship of tumor and normal structures to the
      applicator. This information can be used to optimize the delivery of radiation
      therapy treatments. Thus far, six patients have been scanned using this process.

PMID- 11958909
TI  - Investigations of a minimally invasive method for treatment of spinal
      malignancies with LINAC stereotactic radiation therapy: accuracy and animal
      studies.
AB  - PURPOSE: A new method for stereotactic irradiation of spinal malignancies is
      presented, with evaluations of the theoretic and practical limitations of
      localization accuracy and the implementation of the method in swine. MATERIALS
      AND METHODS: In a percutaneous procedure, a minimum of three small (1.7-mm
      diameter) titanium markers are permanently affixed to a vertebra. Markers are
      localized on biplanar radiographs while isocenter positions are determined on CT.
      An external fiducial frame defines a three-dimensional coordinate system through
      the patient. Radiographs coupled with a rigid body rotation algorithm account for
      daily differences in patient position. Phantom studies were used to verify
      theoretic uncertainty calculations from a simulation program. A swine model was
      used to evaluate the difficulty and duration of the implant technique, the
      suitability of the vertebral process as an implant site, vertebral motion due to
      normal respiration, and the ability to target one vertebra with markers in an
      adjacent vertebra. RESULTS: Theoretic accuracy studies confirmed that
      localization accuracy is a function of marker separation. Phantom studies
      involving 296 measurements showed that individual implants could be localized
      within +/-0.25 mm. The largest targeting error observed in 3,600 measurements of
      100 implant configurations was 1.17 mm. The implant procedure took 5-10 minutes
      per site. No significant migration of implants was observed up to 35 days
      postimplantation, and respiratory motion had no detectable influence on vertebral
      position. Adjacent vertebrae may be useful for targeting one another with a small
      sacrifice in localization accuracy. CONCLUSIONS: The use of implanted markers for
      localization of spinal malignancies has potential for applications in
      stereotactic radiotherapy. Phantom measurements suggest that localization
      accuracy similar to intracranial stereotactic radiotherapy techniques is
      achievable. Swine studies suggest that the implant technique is expedient and
      feasible for tumor targeting purposes.

PMID- 11958910
TI  - Performance evaluation of an 85-cm-bore X-ray computed tomography scanner
      designed for radiation oncology and comparison with current diagnostic CT
      scanners.
AB  - INTRODUCTION: The demand for computed tomography (CT) virtual simulation is
      constantly increasing with the wider adoption of three-dimensional conformal and
      intensity-modulated radiation therapy. Virtual simulation CT studies are
      typically acquired on conventional diagnostic scanners equipped with an external
      patient positioning laser system and specialized planning and visualization
      software. Virtual simulation technology has matured to a point where conventional
      simulators may be replaced with CT scanners. However, diagnostic CT scanner
      gantry bores (typically 65-70 cm) can present an obstacle to the CT simulation
      process by limiting patient positions, compared to those that can be attained in
      a conventional simulator. For example, breast cancer patients cannot always be
      scanned in the treatment position without compromising reproducibility and
      appropriateness of setup. Extremely large patients or patients requiring special
      immobilization or large setup devices are often unable to enter the limited-bore
      gantry. A dedicated 85-cm-bore radiation oncology CT scanner has the potential to
      eliminate these problems. The scanner should provide diagnostic-quality images at
      diagnostic-comparable dose levels. The purpose of this study was to independently
      evaluate the performance of a novel 85-cm-bore CT X-ray scanner designed
      specifically for radiation oncology and compare it against diagnostic-type, 70-cm
      bore scanners that may be used in the same setting. MATERIALS AND METHODS: We
      performed image quality and dosimetric measurements on an 85-cm-bore CT scanner
      (AcQSim CT, Marconi Medical Systems, Inc., Cleveland, OH) and a 70-cm-bore,
      diagnostic-type scanner (UltraZ CT, Marconi Medical Systems, Inc.). Image quality
      measurements were performed using a manufacturer-supplied phantom (Performance
      Phantom, Marconi Medical Systems, Inc.), following the manufacturer's suggested
      testing procedures, and an independent image quality phantom (CATPHAN 500, The
      Phantom Laboratory, New York, NY). The standard image quality parameters
      evaluated for the purpose of comparison were as follows: slice thickness
      accuracy, high-contrast resolution (limiting spatial resolution), low-contrast
      resolution, uniformity and noise, and CT number accuracy and linearity. Standard
      head and body protocols were employed throughout most of our measurements and
      were kept equal between the two scanners. The computed tomography dose index was
      measured for standard head and body imaging protocols using accepted methods and
      procedures. For comparison purposes, data for a diagnostic-type, 70-cm-bore
      scanner (GE HighSpeed CT/i) were extracted from the literature. The results
      obtained for the 85-cm-bore scanner are compared with the following: (1)
      manufacturer-provided autoperformance phantom test results (validating its use
      for routine quality assurance), (2) a similar set of measurements performed on a
      conventional 70-cm-bore, diagnostic-type CT scanner (UltraZ CT, Marconi Medical
      Systems, Inc.), and (3) current available data on other diagnostic-type CT
      scanners (GE HighSpeed CT/i). RESULTS: Head and body doses seem on average to be
      slightly (1-2 cGy) higher for the 85-cm-bore unit than for conventional 70-cm
      units. Measured slice thickness was within acceptable criteria, +/-0.5 mm. There
      does not seem to be any significant difference in high-contrast resolution. Both
      units render a limiting value of approximately 7-8 lp/cm for slice thickness 8-10
      mm. Both units exhibit comparable CT number uniformity, accuracy, and linearity.
      Noise levels seem to be slightly increased (by approximately 0.05-0.2%) for the
      large-bore geometry. Low-contrast resolution for both units was comparable (4.5
      5.5 mm @ 0.35%). All image quality parameters are well within diagnostic
      acceptable levels. CONCLUSION: The overall imaging performance and mechanical
      integrity of the 85-cm-bore scanner are comparable to those of conventional
      diagnostic scanners that may be employed in a radiation oncology setting.

PMID- 11958911
TI  - Dosimetric characteristics of the MammoSite RTS, a new breast brachytherapy
      applicator.
AB  - PURPOSE: A new device has been developed with the goal of making breast
      conserving therapy more widely available, by making breast brachytherapy as
      monotherapy simpler and more accurate. This is the first published report on the
      dosimetric characteristics of this device. MATERIALS AND METHODS: The experience
      of a single institution participating in a multi-institutional trial is reported.
      Twelve patients were enrolled, of whom 8 were treated. Computed tomography scans
      of all 12 patients were obtained before initiation of treatment. A commercial
      three-dimensional planning system was used for retrospective detailed analysis of
      dosimetry, including dose-volume histograms and, in selected patients, skin dose
      distributions. These data were compared to those of a similar group of patients,
      analyzed previously, that was treated with interstitial high-dose-rate
      brachytherapy. RESULTS: Compared with interstitial brachytherapy, the MammoSite
      device resulted in a treatment dose that was less uniform, with a mean dose
      homogeneity index of 0.77 vs. 0.93. Coverage and reproducibility were improved,
      with a mean D90 (minimum dose to 90% of target volume) of 90.0% of prescribed
      dose (SD 0.5, range: 89.2-90.8%) vs. 69.8% (SD 7.3, range: 61.1-83.5%) for
      interstitial brachytherapy. CONCLUSIONS: Reproducible placement was easily
      achieved in this very early experience, indicating a much smaller "learning
      curve" than for interstitial brachytherapy. Because skin doses can be increased
      with the use of this device, caution is indicated, although simple maneuvers can
      significantly reduce skin dose.

PMID- 11958912
TI  - Of scientific physicians and objective knowledge.

PMID- 11958914
TI  - Incorporating lung tumor mobility in radiotherapy planning.

PMID- 11958916
TI  - In regard to Cheng et al., examining prognostic factors of failure in
      nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy:
      impact on future clinical trials. IJROBP 2001;50:717-726.

PMID- 11958919
TI  - In regard to Jeremic et al., IJROBP 2001;50:19-25.

PMID- 11958920
TI  - Efficacy, toxicity, and cost-effectiveness of single-dose versus fractionated
      hemibody irradiation (HBI).

PMID- 11958922
TI  - In regard to Denham et al., is it time for a new formalism to categorize normal
      tissue radiation injury? IJROBP 2001;50:1105-1106.

PMID- 11958925
TI  - Radiation therapy oncology: in regard to Fu et al., IJROBP 2000;48:7-16.

PMID- 11958923
TI  - In response to Drs. Dubben, Beck-Bornholdt, and Llogie.

PMID- 11958926
TI  - On the consistent use of organ definitions and radiobiological models for the
      evaluation of complication probabilities of "tubular" organs.

PMID- 11958927
TI  - Current status of immune mechanisms of killing of intracellular microorganisms.
AB  - The interaction between intracellular pathogens and the mammalian host follows
      different pathways that reflect evolved survival mechanisms of both the pathogen
      and the host to assure each one's own survival. From the host's perspective,
      different immune mechanisms predominate at different stages of infection. Both
      phagocytic and non-phagocytic target cells participate in microbial uptake and,
      in some cases, intracellular destruction. In addition, the development of
      specific immunity ensures sustained activation of intracellular microbicidal
      mechanisms in the target cells, and induction of apoptotic or lytic target cell
      death by cytotoxic T lymphocytes. From the pathogen's perspective, different
      evasion strategies are employed to counteract host defenses. Understanding
      microbial survival strategies and the immune mechanisms that result in killing of
      intracellular pathogens will deepen our insight into the pathogenesis of
      infection that could be applied towards the development of effective vaccination
      and immunotherapy.

PMID- 11958928
TI  - Microbe-induced T cell apoptosis: subversion of the host defense system?
AB  - Cells of multicellular organisms are equipped with a self destruction program
      called apoptosis to ensure homeostasis of the organism. Contraction of the
      lymphocyte compartment following recovery from an infection is controlled by this
      mechanism. But apoptosis of lymphocytes might be an Achilles tendon accessible to
      microbes to subvert the immune system. Evidence is cumulating that microbes use
      this mechanism to destroy microbe-specific T cells. We present an overview of
      microbe-induced T cell apoptosis discussing the consequences for the pathogenesis
      of microbial infection. The conventional role of lymphocytes during infection is
      to impose apoptotic threat to infected cells, the subject of this review
      highlights the opposite, lymphocytes as targets of microbe-induced death.

PMID- 11958929
TI  - Aeromonas hydrophila vacuolating activity in the Caco-2 human enterocyte cell
      line as a putative virulence factor.
AB  - A non-enterotoxigenic strain of Aeromonas hydrophila isolated from diarrheic
      stools of an 8-month-old child was found to cause vacuolation in Caco-2 cells.
      The vacuoles became prominent 60 min after addition of the bacterial culture to
      the cell monolayers and, after 120 min, a complete disruption of the monolayers
      was observed. Cell vacuolation was not detected when Caco-2 monolayers were
      tested with sterile filtrates of overnight cultures of the A. hydrophila
      vacuolating strain AH14846. This strain produced a diffuse adherence pattern in
      Caco-2 cell monolayers, but did not produce detectable cytotonic enterotoxin in
      the suckling mouse test and only produced small quantities of aerolysin. By
      demonstrating the ability to induce vacuolation in mammalian cells of enterocytic
      lineage, the current study raises the possibility that such activity might
      contribute to gastrointestinal symptoms in infections involving Aeromonas strains
      which do not express well-established enterotoxins.

PMID- 11958930
TI  - Physical and genetic map of Enterococcus faecium ATCC19434 and demonstration of
      intra- and interspecific genomic diversity in enterococci.
AB  - A physical map of the Enterococcus faecium ATCC19434 chromosome was constructed
      by NotI, I-CeuI and Sse8387I. The chromosome was a circular DNA of 2600 kb in
      size, and contained six rRNA operons (rrn). The locations and orientations of the
      six rrn operons and 24 different determinants were mapped. Genomes of three
      additional E. faecium strains were also analyzed by I-CeuI digestion, and the
      genome sizes were found to vary from 2550 to 2995 kb. We further investigated the
      genome sizes and number of rrn operons in four E. faecalis, one E. avium, and one
      E. durans strains. The genome sizes were larger than E. faecium: 3000-3250 kb in
      E. faecalis, 3445 kb in E. avium, and 3070 kb in E. durans. E. avium and E.
      durans contained six rrn operons as in E. faecium, but all the E. faecalis
      strains possessed four rrn operons.

PMID- 11958931
TI  - Cloning, nucleotide sequence and expression of the gene encoding the cellulose
      binding protein A (CBPA) of Eubacterium cellulosolvens 5.
AB  - The nucleotide sequence of the gene encoding the cellulose-binding protein A
      (CBPA) of Eubacterium cellulosolvens 5 was determined. The gene consists of an
      open reading frame of 3453 nucleotides and encodes a protein of 1151 amino acids
      with a molecular mass of 126408 Da. The deduced amino acid sequence of CBPA
      contained one domain highly similar to a catalytic domain of glycosyl hydrolases
      belonging to family 9, two linker-like domains and four domains of unknown
      function. Among the four domains of unknown function, the domains 1 and 2 region
      had significant homology in amino acid sequence with the cellulose-binding
      domains in the family 9 glycosyl hydrolases. The cloned gene was inserted into an
      expression vector, pBAD-TOPO, and expressed in Escherichia coli as a fused
      protein. The fused protein was detected by immunoblotting using antiserum against
      CBPA.

PMID- 11958932
TI  - Occurrence of epsilon-poly-L-lysine-degrading enzyme in epsilon-poly-L-lysine
      tolerant Sphingobacterium multivorum OJ10: purification and characterization.
AB  - Epsilon-poly-L-lysine (epsilon-PL)-degrading enzyme was found in the epsilon-PL
      tolerant strain Sphingobacterium multivorum OJ10 and purified to homogeneity. The
      purified enzyme has a molecular mass of approximately 80 kDa. The enzyme
      catalyzed exo-type degradation of epsilon-PL and released L-lysine. The enzyme
      was a Co2+ or Ca2+ ion-activated aminopeptidase.

PMID- 11958933
TI  - Identification to the species level of the plant pathogens Phytophthora and
      Pythium by using unique sequences of the ITS1 region of ribosomal DNA as capture
      probes for PCR ELISA.
AB  - The ribosomal internal transcribed spacer 1 region was sequenced for 10 species
      of Pythium and eight species of Phytophthora. Alignment of the sequences revealed
      considerable sequence microheterogeneity, which was utilized to prepare a capture
      probe of unique sequence for each species. The capture probes were tested by PCR
      ELISA, combining the sensitivity and specificity of the polymerase chain reaction
      (PCR) and enzyme-linked immunosorbent assay (ELISA). The probes were entirely
      species specific, enabling the detection and identification of the amplified DNA
      of species from individual cultures or from mixed samples of the DNAs of two
      different species. This approach to species identification, which provides a
      molecular technology to process large numbers of samples and still identify the
      fungi with a high level of confidence, may greatly reduce the resources and the
      time of highly trained specialists currently needed to identify these important
      species of plant pathogenic fungi.

PMID- 11958934
TI  - Polyphosphate produced in recombinant Escherichia coli confers mercury
      resistance.
AB  - An Escherichia coli strain was generated by fusion of a merA-deleted broad
      spectrum mer operon from Pseudomonas K-62 with a bacterial polyphosphate kinase
      gene (ppk) from Klebsiella aerogenes in vector pUC119. A large amount of the ppk
      specified polyphosphate was identified in the mercury-induced bacterium with the
      fusion plasmid designated pMKB18 but not in the cells without mercury induction.
      These results suggest that the synthesis of polyphosphate as well as the
      expression of the mer genes is mercury-inducible and regulated by merR. The E.
      coli strain with pMKB18 was more resistant to both Hg2+ and C6H5Hg+ than its
      isogenic strain with cloning vector pUC119. The recombinant strain accumulated
      more mercury from Hg2+- and C6H5Hg+-contaminated medium. Hg2+ transported into
      the cytoplasm appeared to be bound by chelation with the polyphosphate produced
      by the recombinant cells. The transported phenylmercury was degraded to Hg2+
      before the chelation since polyphosphate did not directly chelate with C6H5Hg+.
      These results indicate that polyphosphate is capable of reducing the cytotoxicity
      of the transported Hg2+ probably via chelation between polyphosphate and Hg2+.

PMID- 11958935
TI  - Dual cell wall/mitochondria localization of the 'SUN' family proteins.
AB  - The Saccharomyces cerevisiae SUN family gene products, namely Sim1p, Uth1p, Nca3p
      and Sun4p, show a high degree of homology among themselves and are closely
      related to beta-glucosidase of Candida wickerhamii; however, these proteins do
      not bear such an activity. Dithiothreitol-treatment of intact cells induces the
      release of Uth1p, Sun4p and Sim1p from the cell wall. These highly glycosylated
      proteins are thus non-covalently bound to the cell wall. Two of them, Uth1p and
      Sun4p, have also been found in mitochondria. Sub-localization experiments show
      that Uth1p is inserted in the outer mitochondrial membrane and that Sun4p is
      preferentially a matrix protein. The physiological significance of this double
      localization is discussed in relation to the roles of these proteins in different
      cellular processes, namely mitochondrial biogenesis and cell septation.

PMID- 11958936
TI  - Characterization of Azotobacter vinelandii aggregation in submerged culture by
      digital image analysis.
AB  - A simple and accurate method for determining the distribution of sizes of single
      cells and aggregates of Azotobacter vinelandii by image analysis has been
      developed. A staining procedure using methylene blue helps to enhance the
      contrast between aggregates and background without altering aggregate size
      distribution. Sample dilution affected the distribution of the population and
      therefore should be avoided. Mixing and aeration conditions during culture play
      an important role in the aggregation of A. vinelandii. Cells grown under mild
      mixing conditions (unbaffled flasks) presented a thick slime layer and formed
      aggregates of up to 35 microm of average equivalent diameter. In contrast, under
      strong agitation conditions (baffled flasks) practically no aggregates were
      formed throughout cultivation. The method described can be used for the
      characterization of aggregation of other microbial cultures.

PMID- 11958937
TI  - Phylogeny of the filamentous bacterium Eikelboom Type 1851, and design and
      application of a 16S rRNA targeted oligonucleotide probe for its fluorescence in
      situ identification in activated sludge.
AB  - Micromanipulation was used to obtain an isolate (BEN 52) of Eikelboom Type 1851
      from a bulking activated sludge plant. Its 16S rDNA sequence reveals its closest
      relative is 'Roseiflexus castenholzii', a member of the phylum 'Chloroflexi',
      class 'Chloroflexi', previously called the green non-sulfur bacteria. The 16S
      rRNA targeted oligonucleotide probe designed for fluorescence in situ
      hybridisation against this sequence successfully identified filamentous bacteria
      with the morphological features of Type 1851 in activated sludge samples from
      plants in several countries and different operational configurations.

PMID- 11958938
TI  - Cloning and characterization of a major surface protein (MspTL) of Treponema
      lecithinolyticum associated with rapidly progressive periodontitis.
AB  - The gene encoding a major surface protein (MspTL) of Treponema lecithinolyticum,
      a periodontopathogen, was cloned and sequenced. The mspTL gene has a 1770-bp open
      reading frame (ORF) encoding a protein of 590 amino acids with a predicted
      molecular mass of 65 kDa which had a typical prokaryotic signal sequence (19
      amino acids). MspTL showed a high level of homology with major sheath protein
      (MspA) of Treponema maltophilum, phylogenetically the closest relative of T.
      lecithinolyticum. Southern blot analysis indicated that the mspTL gene exists in
      a single copy and Northern blot analysis showed that the mspTL transcript is
      monocistronic. Another ORF located downstream of mspTL was in the same
      orientation and encoded a putative protein, in which the first N-terminal 291
      amino acids were identified. The homologous region of this protein is also a part
      on the T. maltophilum mspA locus.

PMID- 11958939
TI  - Physical and genetic map of the Bacteroides fragilis YCH46 chromosome.
AB  - The chromosome of Bacteroides fragilis strain YCH46 was shown to be a single
      circular DNA molecule of about 5.3 Mb having 16 NotI, seven AscI, and six I-CeuI
      sites. A physical map of the chromosome was constructed by four independent
      experimental approaches: linking clone analysis, cross-Southern hybridization,
      partial restriction digestion, and two-dimensional pulsed-field gel
      electrophoresis. Six rRNA operons and 10 known genes were localized on the
      physical map.

PMID- 11958940
TI  - No animal models of AAA are valid, but some can be very useful.

PMID- 11958941
TI  - Oral sensation of ethanol in a primate model III: responses in the lingual branch
      of the trigeminal nerve of Macaca mulatta.
AB  - Ethanol administered orally has been shown to elicit a powerful response in
      rhesus monkey taste nerves. In this study we focused on the effects of ethanol on
      lingual non-gustatory receptors by recording from 70 single lingual nerve fibers.
      Of these 70 fibers, 54 (78%) responded to one or more concentrations of 0.7-12 M
      ethanol; 16 fibers (22%) were not affected. In 48 (69%) fibers, ethanol increased
      nerve activity, whereas 6 fibers (9%) exhibited suppression, which was displayed
      as a diminished response to mechanical stimulation. The excitatory response was
      characterized by regular impulse activity after a latency of 3-40 sec. With
      higher concentrations of ethanol, the latency became shorter, and the impulse
      activity evoked became higher. In many fibers the response peaked and ceased
      before the end of the 52-sec long-stimulation period. Most of the fibers affected
      by ethanol responded to light touch and cooling. During repeated touch, ethanol
      initially potentiated and then abolished the response to mechanical stimulation.
      Methanol and propanol gave similar results. Butanol only inhibited nerve
      activity.

PMID- 11958943
TI  - Effects of adolescent ethanol exposure on ethanol consumption in adult rats.
AB  - Ethanol exposure during early development could predispose an individual to
      increased ethanol consumption. Given the high prevalence of adolescent ethanol
      abuse, it is important to assess the potential impact of adolescent ethanol
      exposure on the development of alcohol drinking. The following study was designed
      to assess the initiation of ethanol consumption in adult rats after exposure to
      ethanol vapors during adolescence. Male Sprague-Dawley rats (n = 23) were exposed
      to ethanol vapor for 12 h per day for 10 consecutive days between postnatal days
      30 and 40. Ethanol vapor exposure maintained blood ethanol levels averaging 250
      mg/dl. All rats were subsequently trained to self-administer ethanol after a 52
      day withdrawal period. When ethanol consumption was assessed in the adult rats
      (>3 months old) there were no significant differences in initiation or
      maintenance of ethanol self-administration between ethanol-exposed and control
      rats. In addition, there were no group differences in the ability of a noise
      stressor presented before the drinking session to transiently decrease ethanol
      intake. Overall, these findings indicate that forced exposure to ethanol vapor
      during adolescence does not seem to be sufficient to alter initiation or
      maintenance of limited-access ethanol self-administration.

PMID- 11958942
TI  - Concentration of ethanol and other volatile compounds in the blood of acutely
      poisoned alcoholics.
AB  - The presence of volatile compounds, such as acetone, acetaldehyde, methanol,
      ethanol, isopropanol, and n-propanol, in the blood of 169 acutely poisoned
      alcoholics was determined. The clinical diagnosis of addiction was made on the
      basis of a patient interview as well as physical, psychological, and psychiatric
      examination. At the time of the patients' admission to the clinic, the mean
      concentration of ethanol in blood was 3.14 +/- 1.10 g/l and its elimination rate
      in the studied group was 0.27 +/- 0.08 g/kg/hr, an elimination rate significantly
      higher (P <.001) than that of social drinkers, which averages to 0.014 +/- 0.04
      g/kg/h. The presence of other volatile compounds in the blood of alcohol-addicted
      patients is common. The calculated elimination rate constant of methanol was
      about 0.2 h(-1). This rate seems to indicate that, in heavy drinkers, the
      elimination of methanol may be relatively fast even if the ethanol concentration
      is above 1 g/l. The elimination of other volatile compounds can be accelerated by
      large doses of ethanol, although it is not correlated with actual blood ethanol
      level. Moreover, in most of the blood samples with a methanol concentration below
      10 mg/l, the measured concentration of acetone was below 7 mg/l and that of
      isopropanol was below 2 mg/l.

PMID- 11958944
TI  - Do Spanish patients drink alcohol while undergoing treatment with
      benzodiazepines?
AB  - In this study, we analyzed patterns of combined benzodiazepines and alcohol use
      among the Spanish general population over the age of 16 years. The study was
      based on information from the 1997 Spanish National Household Health Survey. A
      total of 6,396 persons over 16 years of age, a representative sample of
      noninstitutionalized Spaniards, were surveyed. One percent of the population are
      consumers of benzodiazepines and daily drinkers of alcohol; fundamentally, these
      consumers are men, of whom 15.4% drink alcohol at a high level (>50 units/week).
      Findings show the frequency of concurrent use of benzodiazepines and alcohol by
      the Spanish population.

PMID- 11958945
TI  - Immune measures in alcohol-dependent persons with minor health abnormalities.
AB  - Altered immunity is commonly associated with alcoholism. However, few studies
      have contrasted alcoholism per se with effects of the medical sequelae or
      comorbidities of alcoholism on the immune system. We previously found few
      differences in lymphocyte subsets, mitogen response, granulocytic phagocytosis,
      or natural killer cell activity when we compared healthy urban alcohol-dependent
      individuals with community control subjects. To begin to explore the role of
      medical factors, 11 alcohol-dependent persons derived from the same clinical
      population but showing mild medical abnormalities (AMMAs), primarily abnormal
      liver function test results, were compared with the previously described 44
      alcohol-dependent persons without medical dysfunctions and 34 nonabusing
      community persons. The AMMAs had lower numbers of CD45RA + inducer
      suppressor/naive cells (P <.02) and HLA-DR+-activated T cells (P <.04) compared
      with findings for nonabusers and higher percentages of circulating CD56 + natural
      killer cells (P <.03). Mitogen responses to concanavalin A, phytohemagglutinin,
      and pokeweed mitogen; natural killer cell activity; and granulocyte functions did
      not differ across groups. The AMMAs reported higher alcohol consumption than that
      reported by the other groups. The findings seem to indicate that mild medical
      conditions, or conditions linked to abnormal liver function test results, are
      associated with some of the immune alterations reported in alcohol-dependent
      persons. Immune changes, even among chronically alcohol-dependent persons, may
      occur along a continuum associated with total alcohol exposure and intercurrent
      physiologic abnormalities. Clinical studies may need to control for such mild
      abnormalities when investigating alcohol-immune relationships, and clinical
      interventions may be especially important for alcohol-dependent individuals who
      show early signs of compromised health.

PMID- 11958946
TI  - Low doses of naltrexone reduce palatability and consumption of ethanol in outbred
      rats.
AB  - The opioid antagonist naltrexone, at doses of 1 and 3 mg/kg, has been shown to
      decrease the palatability and consumption of 10% ethanol in rats. However, a dose
      of 0.5 mg/kg of naltrexone has produced equivocal results. The purpose of the
      present study was to clarify the effects of low doses of naltrexone (0.0
      [control], 0.25, 0.50, 0.75, and 1.0 mg/kg) on palatability and consumption of
      10% ethanol. Sixty-four, male, Long-Evans hooded rats were divided into five
      groups matched for ethanol consumption. Each rat was injected over four
      consecutive days with one of five doses of naltrexone exactly 30 min before taste
      reactivity testing with 10% ethanol. When reactivity testing was completed, rats
      were acclimated to drink during a period of restricted access to fluid under
      conditions of mild fluid deprivation. Then, on four consecutive test days, rats
      were injected with naltrexone 10 min before 10% ethanol was made available for 30
      min. Although each dose of naltrexone decreased ingestive responding to 10%
      ethanol over four days, this effect was not statistically reliable. However, all
      doses of naltrexone produced significant increases in aversive responding to the
      ethanol solution. Naltrexone, at the three highest doses, produced significant
      decreases in consumption of 10% ethanol. These results were consistent with the
      interpretation that naltrexone, even at low doses, reliably reduces palatability
      and consumption of 10% ethanol.

PMID- 11958947
TI  - Short- and long-term effects of acetaldehyde on plasma.
AB  - The effect of low concentrations of acetaldehyde on activated partial
      thromboplastin time (APTT) and prothrombin time (PT) of Accuclot coagulation
      plasmas was monitored over a prolonged time to mimic effects observed in
      alcoholism. A prolongation of the APTT from 31.9 +/- 0.7 s to 32.6 +/- 0.9 s (n =
      8; P =.007) was observed after a 30-min preincubation time with 140 microM
      acetaldehyde. However, a minimum of 3.6 mM acetaldehyde was required to extend
      the APTT from 36.6 +/- 1.0 s to 41.2 +/- 0.8 s (P =.001) over an 18-h exposure
      time. Plasma acetaldehyde levels as low as 2.24 mM caused elevation of PTs from
      12.5 +/- 0.5 s to 14.4 +/- 0.2 s (P =.005) after a 24-h preincubation time. These
      findings seem to indicate that short-term contact of acetaldehyde with plasma,
      probably yielding reversible interactions, may interfere with APTTs to a greater
      extent than long-term contact, which would presumably yield stable, irreversible
      interactions. In comparing the effects of 8.94, 17.9, 89.4, and 447 mM
      acetaldehyde on the PTs of Level I, II, and III plasma, the PTs were most
      increasingly prolonged in Level III plasma and least prolonged in Level I plasma
      at each acetaldehyde concentration, although the plasmas have comparable protein
      concentrations. These findings seem to indicate that coagulation factors are
      sensitive to inactivation by acetaldehyde.

PMID- 11958948
TI  - Catecholamine depletion by reserpine blocks the anxiolytic actions of ethanol in
      the rat.
AB  - Neurochemical investigations of the anti-anxiety action of ethanol demonstrate
      that increased dopaminergic, noradrenergic, and serotonergic activity mediates
      the anxiolytic actions of ethanol. Results of studies with animals and human
      beings also confirm an involvement of the sympathetic nervous system in the
      behavioral actions of ethanol. Because enhanced sympathetic activity increases
      the release of norepinephrine from sympathetic terminals, the interruption of
      normal sympathetic activity might disrupt the anxiolytic action of ethanol. The
      present study examined the effect of chemical sympathectomy by reserpine
      pretreatment on the subsequent anxiolytic action of ethanol. Seventy-one, female,
      Sprague-Dawley rats were administered reserpine (0 or 5 mg/kg), followed 17-19 h
      later by ethanol (0, 0.5, or 1.0 g/kg). Animals were then tested in the elevated
      plus maze. Compared with saline pretreatment, which did not attenuate the
      anxiolytic actions of a 1.0-g/kg dose of ethanol, reserpine pretreatment
      completely blocked the anxiolytic action of a 1.0-g/kg dose of ethanol.
      Reserpine, by itself, did not possess anxiolytic or anxiogenic actions. Because
      the anxiolytic action of ethanol involves increased catecholamine activity and
      the depletion of norepinephrine and dopamine from sympathetic nerve terminals by
      reserpine blocked the anxiolytic action of ethanol, it is concluded that the
      anxiolytic action of ethanol requires the presence of normal catecholamine
      activity. We suggest that prostaglandin activity normally evoked by enhanced
      sympathetic nervous system activity might be involved in the anxiolytic action of
      ethanol.

PMID- 11958949
TI  - Role of mitochondria in alcoholic liver injury.
AB  - Oxidative stress and oxygen-derived free radicals are well known to play an
      important role in the pathogenesis of ethanol-associated liver injury. Active
      oxidants produced during ethanol metabolism induce mitochondrial membrane
      depolarization and permeability changes in cultured hepatocytes. These
      mitochondrial alterations (loss of DeltaPsim and mitochondrial permeability
      transition [MPT]) are now recognized as a key step in apoptosis. In recent
      studies, including ours, the MPT has been identified as a key step for the
      induction of mitochondrial cytochrome c release and caspase activation by
      ethanol. In addition, chronic and/or acute ethanol modulates intracellular,
      especially mitochondrial, antioxidant levels, leading to the increased
      susceptibility to alcoholic liver injury induced by several apoptotic stimuli. In
      this review, we address the mechanism of mitochondrial alterations and liver
      injury induced by ethanol.

PMID- 11958950
TI  - Nacystelyn inhibits oxidant-mediated interleukin-8 expression and NF-kappaB
      nuclear binding in alveolar epithelial cells.
AB  - Nacystelyn (NAL), a recently developed lysine salt of N-acetyl-L-cytokine (NAC)
      has mucolytic and antioxidant properties. In this study, we investigated the
      effect of NAL upon oxidant-mediated interleukin (IL)-8 release and the activation
      of the redox-sensitive transcription factors AP-1, NF-kappaB, and C/EBP in a
      human alveolar epithelial cell line (A549). NAL (5 mM) enhanced intracellular
      glutathione (GSH) after 4 h and abolished H(2)O(2)-induced IL-8 release from A549
      cells. This was associated with inhibition of NF-kappaB and C/EBP DNA-binding,
      measured by the Electrophoretic Mobility Shift Assay (EMSA). NAL also abolished
      the transcriptional activation of IL-8 in an IL-8-chloramphenicol acetyl
      transferase (CAT) reporter system, transfected into A549 cells. Supernatants
      obtained from H(2)O(2)-treated A549 cells induced chemotaxis of polymorphonuclear
      neutrophils, which could be inhibited by co-incubation with NAL. These data
      indicate that NAL may be used to modulate pro-inflammatory process by inhibiting
      cytokine release in the lungs and thus has therapeutic potential in inflammatory
      lung diseases.

PMID- 11958951
TI  - Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from
      old mice: role of peroxynitrite.
AB  - Vitamin E inhibits cyclooxygenase activity in macrophages from old mice by
      reducing peroxynitrite production. PGE(2) is a proinflammatory mediator that has
      been linked to a variety of age-associated diseases such as cancer, arthritis,
      and cardiovascular disease. Furthermore in the aged, increased cyclooxygenase
      (COX)-2-mediated PGE(2) production contributes to decline in T-cell-mediated
      function. Previously we reported that increased macrophage PGE(2) production in
      the aged is due to higher COX-2 activity and that supplementation with vitamin E
      significantly reduced the age-associated increase in macrophage PGE(2) production
      posttranslationally without changing COX-2 expression. Peroxynitrite, a product
      of nitric oxide (NO) and superoxide (O(-)(2)), increases the activity of COX
      without affecting its expression. Thus, we investigated if vitamin E inhibits COX
      activity through decreasing peroxynitrite formation. Macrophages from old mice
      had higher PGE(2) levels, COX activity, and NO levels than those from young mice,
      all of which were significantly reduced by vitamin E. When added individually,
      inhibitors of NO and O(-)(2) did not significantly reduce COX activity; however,
      when the inhibitors were combined, COX activity was significantly reduced in
      macrophages from old mice fed 30 ppm vitamin E. Increasing NO levels alone using
      SNAP or O(-)(2) levels, using X/XO, had no effect; however, increasing
      peroxynitrite levels using Sin-1 or X/XO + SNAP significantly increased COX
      activity in macrophages from old mice fed 500, but not those fed 30 ppm vitamin
      E. These data strongly suggest that peroxynitrite plays an important role in the
      vitamin E-induced inhibition of COX activity. These findings have important
      implications for designing interventions to reverse and/or delay age-associated
      dysregulation of immune and inflammatory responses and diseases associated with
      them.

PMID- 11958952
TI  - Superoxide modification and inactivation of a neuronal receptor-like complex.
AB  - Excessive superoxide (O(-)(2)) formation is toxic to cells and organisms. O(-)(2)
      reacts with either iron-sulfur centers or cysteines (Cys) of cytoplasmic
      proteins. Reactions with membrane proteins, however, have not been fully
      characterized. In the present studies, the reaction of O(-)(2) with a protein
      complex that has glutamate/N-methyl-D-aspartate (NMDA) receptor characteristics
      and with one of the subunits of this complex was examined. Exposure of the
      complex purified from neuronal membranes and the recombinant glutamate-binding
      protein (GBP) subunit of this complex to the O(-)(2)-generating system of
      xanthine (X) plus xanthine oxidase (XO) caused strong inhibition of L
      [3H]glutamate binding. Inhibition of glutamate binding to the complex and GBP by
      O(-)(2) was greater than that produced by H(2)O(2), another product of the X plus
      XO reaction. Mutation of two cysteine (Cys) residues in recombinant GBP
      (Cys(190,191)) eliminated the effect of O(-)(2) on L-[3H]glutamate binding. Both
      S-thiolation reaction of GBP in synaptic membranes with [35S]cystine and reaction
      of Cys residues in GBP with [3H]NEM were significantly decreased after exposure
      of membranes to O(-)(2). Inhibition of cysteylation of membrane GBP by O(-)(2)
      was still observed after iron chelation by desferrioxamine, albeit diminished,
      and was not altered by the presence of catalase. Overall, the results indicated
      that GBP exposure to O(-)(2) modified Cys residues in this protein. The
      modification was not characterized but it was probably that of disulfide
      formation.

PMID- 11958953
TI  - Acute cadmium exposure induces stress-related gene expression in wild-type and
      metallothionein-I/II-null mice.
AB  - This study examined the effect of acute cadmium on stress-related gene expression
      and free radical production in wild-type and metallothionein-I/II-null (MT-null)
      mice. Atlas Toxicology arrays showed that acute cadmium (40 micromol/kg as
      CdCl(2), ip for 3 h) markedly increased the expression of genes encoding heat
      shock proteins, heme oxygenase-1, and genes in response to DNA damage/repair. The
      expression of genes encoding cytochrome P450 enzymes, UDP
      glucuronosyltransferases, Mn-superoxide dismutase, and catalase was suppressed by
      cadmium. MT-null mice were more sensitive than wild-type mice to cadmium-induced,
      stress-related gene expression, in accord with greater activation of
      transcription factor AP-1 and phosphorylated JNK and ERK. To evaluate free
      radical production, mice were simultaneously given the spin trap agent, N-tert
      butyl-alpha-phenylnitrone (PBN, 250 mg in DMSO/kg, ip) with cadmium, and livers
      were removed 30 min later for PBN-trapped radical extraction with
      chloroform:methanol (2:1), and detected with electron spin resonance (ESR).
      Cadmium treatment caused detectable ESR signals for PBN adducts as well as lipid
      peroxidation in the liver similarly in both wild-type and MT-null mice. Thus, the
      mechanism of acute cadmium toxicity involves multiple facets including oxidative
      damage and aberrant gene expression, and absence of MT exacerbates Cd-induced
      aberrant gene expression.

PMID- 11958954
TI  - N-acetyl-L-cysteine inhibits 26S proteasome function: implications for effects on
      NF-kappaB activation.
AB  - Ionizing radiation shares with cytokines, such as TNF-alpha, an ability to
      generate free radicals in cells and activate downstream proinflammatory responses
      through NF-kappaB-dependent signal transduction pathways. Support for the role of
      free radicals in triggering such responses comes from the use of free radical
      scavengers like N-acetyl-L-cysteine (NAC). The nature of the link between free
      radical generation and NF-kappaB activation is, however, unclear. In this study,
      we explore the possibility that scavenging of free radicals by NAC might not be
      the mechanism by which it inhibits NF-kappaB activation, but rather that NAC acts
      through inhibition of proteasome function. The effect of NAC on the chymotryptic
      function of the 26s and 20s proteasome complex was measured in extracts from EVC
      304 bladder carcinoma cells by assessing degradation of fluorogenic substrates.
      NAC inhibited 26s but not 20s proteasome activity, suggesting that it interferes
      with 19s regulatory subunit function. NAC blocked radiation-induced NF-kappaB
      activity in ECV 304 cells and RAW 264.7 macrophages, as measured by a gel shift
      assay, at doses that inhibited proteasome activity. This provides a possible
      mechanism whereby NAC could block NF-kappaB activation and affect the expression
      of other molecules that are dependent on the ubiquitin/proteasome system for
      their degradation, other than by scavenging free radicals.

PMID- 11958955
TI  - Aggregation of alpha-synuclein induced by the Cu,Zn-superoxide dismutase and
      hydrogen peroxide system.
AB  - Alpha-synuclein is a major component of the abnormal protein aggregation in Lewy
      bodies of Parkinson's disease (PD) and senile plaques of Alzheimer's disease
      (AD). Previous studies have shown that the aggregation of alpha-synuclein was
      induced by copper (II) and H(2)O(2) system. Since copper ions could be released
      from oxidatively damaged Cu,Zn-superoxide dismutase (SOD), we investigated the
      role of Cu,Zn-SOD in the aggregation of alpha-synuclein. When alpha-synuclein was
      incubated with both Cu,Zn-SOD and H(2)O(2), alpha-synuclein was induced to be
      aggregated. This process was inhibited by radical scavengers and spin trapping
      agents such as 5,5'-dimethyl 1-pyrolline N-oxide and tert-butyl-alpha
      phenylnitrone. Copper chelators, diethyldithiocarbamate and penicillamine, also
      inhibited the Cu,Zn-SOD/H(2)O(2) system-induced alpha-synuclein aggregation.
      These results suggest that the aggregation of alpha-synuclein is mediated by the
      Cu,Zn-SOD/H(2)O(2) system via the generation of hydroxyl radical by the free
      radical-generating function of the enzyme. The Cu,Zn-SOD/H(2)O(2)-induced alpha
      synuclein aggregates displayed strong thioflavin-S reactivity, reminiscent of
      amyloid. These results suggest that the Cu,Zn-SOD/H(2)O(2) system might be
      related to abnormal aggregation of alpha-synuclein, which may be involved in the
      pathogenesis of PD and related disorders.

PMID- 11958956
TI  - The nitrone spin trap PBN alters the cellular response to H(2)O(2): activation of
      the EGF receptor/ERK pathway.
AB  - The nitrone spin trap PBN has been shown to protect neuronal cells from reactive
      oxygen species both in culture and in vivo. As an approach to understanding the
      molecular mechanisms by which PBN may function to protect cells, we examined
      whether PBN alters the cellular response to reactive oxygen species. H(2)O(2)
      stimulation of PC-12 cells results in weak activation of both the ERK and JNK
      signal transduction pathways. PBN pretreatment of PC-12 cells, followed by
      H(2)O(2) stimulation, results in strong and selective activation of the pro
      survival ERK pathway. H(2)O(2) induction of ERK activity in PBN-pretreated cells
      was shown to be dependent on extracellular Ca(+2) influx. Further analysis of the
      ERK pathway showed that in PBN-pretreated cells, EGF receptor and the adapter
      protein SHC were phosphorylated in a Ca(+2)-dependent, ligand-independent manner
      following H(2)O(2) stimulation. Interestingly, H(2)O(2) stimulation of PBN
      pretreated cells results in only 30% of the increase in intracellular Ca(+2) as
      compared to untreated cells following H(2)O(2) stimulation. These data suggest a
      model in which PBN attenuates H(2)O(2)-induced Ca(+2) entry, yet magnifies or
      alters Ca(+2) action, resulting in the activation of the EGF receptor/ERK
      pathway.

PMID- 11958958
TI  - The role of lateral premotor-cerebellar-parietal circuits in motor sequence
      control: a parametric fMRI study.
AB  - Functional characterisation of higher order motor systems can be obtained by
      modulating the processing demands imposed onto relevant motor circuitries. Here
      we performed whole-brain functional magnetic resonance imaging (fMRI) and
      parametric statistical analyses in eight healthy volunteers to study task-related
      recruitment of motor circuits associated with unilateral finger movement
      sequences of increasing length and complexity, but with equal basic motor
      parameters. Statistical parametric mapping software was applied for analysis.
      Categorical analysis of the main effect of motor action showed cerebral
      activation in the established cortical and subcortical motor network. Parametric
      analyses of the blood-oxygen-level-dependent (BOLD) contrast revealed significant
      signal increases correlating to sequence length and complexity in a subset of
      activated areas, notably contralateral ventral and dorsal premotor cortex,
      bilateral superior parietal cortex, left inferior frontal gyrus/Broca's area,
      right dentate nucleus, and left visual association cortex. These data underscore
      the importance of ventral premotor-cerebellar-parietal circuits in processing
      length and complexity of sequential finger movements.

PMID- 11958957
TI  - Electrophysiological correlates of visual categorization: evidence for cognitive
      dysfunctions in early Parkinson's disease.
AB  - Our aim was to examine the electrophysiological correlates of perceptual
      categorization in Parkinson's disease (PD). We recorded visual event-related
      potentials (ERPs) in a natural scene categorization task in drug naive idiopathic
      PD patients and healthy control subjects. In the control group, there was a
      significant early difference (150-250 ms poststimulus) between ERPs elicited by
      pictures containing animals and scenes without animals. In spite of relatively
      preserved basic-level visual functions, this was not observable in the PD group.
      These results raise the possibility for striatal contributions to visual
      categorization and may provide a novel protocol for further clinical studies.

PMID- 11958959
TI  - Computational modeling of pair-association memory in inferior temporal cortex.
AB  - Distinctive neuronal activities related to visual stimulus-stimulus association
      have been found in the inferior temporal (IT) cortex of monkeys. They provide an
      important clue to elucidating the memory mechanisms of the brain, but do not
      accord with existing neural network models. In the present paper, we clarify the
      computational principle required for reproducing the empirical data and construct
      a biologically feasible model that learns and performs a delayed pair-association
      task. This model is composed of two neural networks, association network N1 and
      trainer network N2, and pair-association memories are formed by their
      interactions. Specifically, N2 receives the output of N1 in addition to an
      external input, and sends a learning signal back to N1; this signal works as a
      guide for shifts in output pattern or state transitions of N1, and memory traces
      are engraved along its path, so that a trajectory attractor connecting from the
      cue-coding to the target-coding state is formed in N1. Computer simulation shows
      that the model not only distinguishes the target in the task, but also explains
      the activity of the IT neurons very well. It is reasonable to presume that N1 and
      N2 correspond to area TE and the rhinal cortex, respectively; based on this
      theory, we explain some physiological findings on learning and memory, and also
      make several predictions.

PMID- 11958960
TI  - Shadows of artistry: cortical synchrony during perception and imagery of visual
      art.
AB  - Functional and topographical differences between two groups, artists and non
      artists, during the performances of visual perception and imagery of paintings
      were presented by means of EEG phase synchrony analysis. In artists as compared
      with non-artists, significantly higher phase synchrony was found in the high
      frequency beta and gamma bands during the perception of the paintings; in the low
      frequency bands (primarily delta), phase synchrony was mostly enhanced during
      imagery. Strong decreases in phase synchrony of alpha were found primarily in
      artists for both tasks. The right hemisphere was found to present higher
      synchrony than the left in artists, whereas hemispheric asymmetry was less
      significant in non-artists. In the artists, enhanced synchrony in the high
      frequency band is most likely due to their enhanced binding capabilities of
      numerous visual attributes, and enhanced synchrony in the low frequency band
      seems to be due to the higher involvement of long-term visual memory mostly in
      imagery. Thus, the analysis of phase synchrony from EEG signals yields new
      information about the dynamical co-operation between neuronal assemblies during
      the cognition of visual art.

PMID- 11958961
TI  - Dividing attention between form and motion during transparent surface perception.
AB  - Attending to objects implies the concurrent process of features that are analyzed
      in different visual subsystems or domains. Previous works have shown that
      attention cannot be simultaneously directed to the components of motion present
      in two transparent surfaces [M. Valdes et al., Cognition 66 (1998) B13-B23], even
      though they occupy overlapping regions of space. In this paper, possible across
      domain effects in object-based attention were examined using a conjunction of
      form and motion in transparent superimposed surfaces. After directing attention
      to one surface, different combinations of motion and form judgements were
      performed. If both attributes belonged to the same surface, no interference was
      found. If the two judgements concerned features from different surfaces, a large
      performance cost was present for the attribute belonging to the uncued surface.
      The fact that these effects cut across feature domains supports the integrated
      competition hypothesis [J. Duncan, Attention and Performance XVI, The MIT Press,
      1996, pp. 549-578].

PMID- 11958962
TI  - Frontal-parietal event-related potential changes associated with practising a
      novel visuomotor task.
AB  - Learning novel visuomotor tasks requires precise processing and transformation of
      incoming sensory information to produce accurate motor responses. The present
      study characterized neural activity associated with sensorimotor processes during
      novel visuomotor learning. We hypothesized that the acquisition of a visuomotor
      skill would be accompanied by experience-dependent modulation of sensorimotor
      cortical activity. Subjects controlled a cursor on a computer screen with a
      joystick. With the goal to move the cursor to a cued target after a brief delay,
      the relationship between joystick and cursor movement was manipulated such that
      joystick movement controlled cursor velocity, not displacement (rate task).
      Individual trials in this task were further divided into early (rate1) and late
      (rate2) blocks. Event-related potentials (ERPs) were averaged to target
      presentation, the cue for movement, and movement onset. Subjects were more
      accurate after practice in late rate2 compared to early rate1 blocks. ERPs
      associated with movement onset were larger in amplitude and occurred earlier over
      centroparietal sites following practice. In contrast, ERPs to the cue to move
      were enhanced frontocentrally initially and diminished with practice. The results
      suggest that practice on a novel visuomotor task is associated with changes in
      frontoparietal networks involved in motor preparation and sensorimotor
      integration. Specifically, practice-related enhancement of movement-related ERPs
      supports experience-dependent alterations in the network subserving motor
      preparation.

PMID- 11958963
TI  - Spatial imagery in deductive reasoning: a functional MRI study.
AB  - Various cognitive theories aim to explain human deductive reasoning: (1) mental
      logic theories claim syntactic language-based proofs of derivation, (2) the
      mental model theory proposes cognitive processes of constructing and manipulating
      spatially organized mental models, and (3) imagery theories postulate that such
      abilities are based on visual mental images. To explore the neural substrates of
      human deductive reasoning, we examined BOLD (blood oxygen level dependent)
      contrasts of twelve healthy participants during relational and conditional
      reasoning with whole-brain functional magnetic resonance imaging (fMRI). The
      results indicate that, in the absence of any correlated visual input, reasoning
      activated an occipitoparietal-frontal network, including parts of the prefrontal
      cortex (Brodmann's area, BA, 6, 9) and the cingulate gyrus (BA 32), the superior
      and inferior parietal cortex (BA 7, 40), the precuneus (BA 7), and the visual
      association cortex (BA 19). In the discussion, we first focus on the activated
      occipito-parietal pathway that is well known to be involved in spatial perception
      and spatial working memory. Second, we briefly relate the activation in the
      prefrontal cortical areas and in the anterior cingulate gyrus to other imaging
      studies on higher cognitive functions. Finally, we draw some general conclusions
      and argue that reasoners envisage and inspect spatially organized mental models
      to solve deductive inference problems.

PMID- 11958964
TI  - Neural activation during an explicit categorization task: category- or feature
      specific effects?
AB  - Previous lesion-deficit and functional imaging studies have suggested that there
      are distinct category-specific regions within the human brain. Using functional
      magnetic resonance imaging, we tested this claim with a task in which
      participants decided if two items, represented by words, were members of the same
      category. Signal changes detected for all pairs of items that were from the same
      category and for tool pairs were found in rostromedial BA 6, rostral cingulate,
      and at the BA 6/44 and BA 45/46 junctions. Activation was seen in BA 6 and the
      left BA 6/44 junction for fruits and vegetables pairs and only in rostromedial BA
      6 for animal pairs. The common signal changes in the frontal lobes (BA 6/44) for
      the categories of fruits and vegetables and tools suggest that this region may be
      organized in a feature-specific, as opposed to a category-specific, manner.

PMID- 11958966
TI  - Action-based distractor effects on the manual response times of chimpanzees
      during discrimination tasks.
AB  - Two chimpanzees performed visual search and simple discrimination tasks in which
      manual pointing to the target stimulus was required. To clarify the action-based
      interference effects of the distractors, response time data were analyzed on the
      basis of the relationship among the positions of the target, distractors, and
      hand. In both tasks, clear action-based interference effects were observed.
      Firstly, distractors along the path of the manual response to the target caused
      greater interference (the response-path effect). Secondly, when distractors were
      located ipsilateral to the responding hand, response times were longer (the
      ipsilateral effect). These results are consistent with previous studies on
      selective reaching in humans, and they suggest that manual responses in
      chimpanzees are controlled by action-centered attention as is the case for
      humans.

PMID- 11958965
TI  - Age-related changes in fronto-parietal networks during spatial memory: an ERP
      study.
AB  - Spatial attention and memory were compared in young and old subjects using non
      delayed and delayed matching-to-sample tests. Both young and older subjects
      revealed a right hemisphere superiority for spatial processing. Older subjects
      were as accurate as young controls in the non-delay task supporting preserved
      attention ability in this spatial task. However, older subjects were impaired at
      3 s retention intervals supporting an encoding and/or retrieval deficit in
      spatial memory. Stimulus evaluation demands were highest in the non-delay task
      and younger subjects generated the largest posterior P3 in this condition plus an
      additional frontal P3. The frontal P3 was reduced in amplitude in the delay tasks
      in the young subjects. Retention of spatial information during the delay period
      was characterized by a negative slow wave maximal over Pz that predicted later
      memory performance and was enhanced in those subjects with high memory
      performance. Conversely, older subjects generated a frontal P3 in both delay and
      non-delay conditions and a reduced sustained posterior scalp negativity in some
      delay conditions. The results support age-related alterations in frontal-parietal
      networks during spatial memory.

PMID- 11958967
TI  - Is experimental motion blindness due to sensory suppression? An ERP approach.
AB  - Recent psychophysical studies have revealed attentional modulation of visual
      motion perception and interest now focuses on the locus of this interaction.
      Using event-related brain potentials (ERPs) we examined whether transient motion
      blindness evoked in a dual task [Vision Res. 41 (2001) 1613-1617] is related to a
      selection process occurring at the stage of sensory processing or at a higher
      level. In our paradigm, a particular change of colour of the fixation point cued
      the subject to detect a brief episode of coherent random dot motion embedded in a
      succession of episodes of incoherent motion. Detection of the coherent motion was
      significantly impaired when it occurred simultaneously with the colour cue, and
      recovered over the subsequent 300 ms. This functional relationship was reflected
      in the amplitude of a sensory, motion-evoked component (N200), and in a late
      positive complex (P300). However, a direct comparison of ERPs produced by stimuli
      that were detected or missed revealed differences only in the P300 component.
      These results indicate that attenuation of sensory motion processing does not
      account for this transient, attention-induced deficit in visual motion
      perception.

PMID- 11958968
TI  - Effect of deviant probability and interstimulus/interdeviant interval on the
      auditory N1 and mismatch negativity in the cat auditory cortex.
AB  - In passive oddball paradigm the effects of changes in interstimulus/interdeviant
      interval (ISI; IDI) and deviant probability were investigated on mismatch
      negativity (MMN), auditory N1 wave and the exogenous P1 component of the auditory
      event-related potential in the cat. An epidural electrode matrix was chronically
      implanted over the auditory fields of the neocortex, and the amplitudes of the
      aforementioned components were measured in the location of their amplitude
      maxima. Dependence of the MMN both on the ISI and IDI as well as deviant
      probability was revealed, while the amplitude of the P1 and N1 showed dependence
      merely on the ISI. This method can be used for separation of the two negative,
      often overlapping components in the cat.

PMID- 11958969
TI  - Increased dopamine tone during meditation-induced change of consciousness.
AB  - This is the first in vivo demonstration of an association between endogenous
      neurotransmitter release and conscious experience. Using 11C-raclopride PET we
      demonstrated increased endogenous dopamine release in the ventral striatum during
      Yoga Nidra meditation. Yoga Nidra is characterized by a depressed level of desire
      for action, associated with decreased blood flow in prefrontal, cerebellar and
      subcortical regions, structures thought to be organized in open loops subserving
      executive control. In the striatum, dopamine modulates excitatory glutamatergic
      synapses of the projections from the frontal cortex to striatal neurons, which in
      turn project back to the frontal cortex via the pallidum and ventral thalamus.
      The present study was designed to investigate whether endogenous dopamine release
      increases during loss of executive control in meditation. Participants underwent
      two 11C-raclopride PET scans: one while attending to speech with eyes closed, and
      one during active meditation. The tracer competes with endogenous dopamine for
      access to dopamine D2 receptors predominantly found in the basal ganglia. During
      meditation, 11C-raclopride binding in ventral striatum decreased by 7.9%. This
      corresponds to a 65% increase in endogenous dopamine release. The reduced
      raclopride binding correlated significantly with a concomitant increase in EEG
      theta activity, a characteristic feature of meditation. All participants reported
      a decreased desire for action during meditation, along with heightened sensory
      imagery. The level of gratification and the depth of relaxation did not differ
      between the attention and meditation conditions. Here we show increased striatal
      dopamine release during meditation associated with the experience of reduced
      readiness for action. It is suggested that being in the conscious state of
      meditation causes a suppression of cortico-striatal glutamatergic transmission.
      To our knowledge this is the first time in vivo evidence has been provided for
      regulation of conscious states at a synaptic level.

PMID- 11958970
TI  - Relating semantic and episodic memory systems.
AB  - Episodic and semantic memory are two forms of declarative memory which appear to
      function in distinct yet interdependent ways. Here we provide direct evidence for
      a functional relationship between these two memory systems by showing that left
      lateral temporal lobe regions involved in semantic memory play an important role
      in accurate episodic memory retrieval.

PMID- 11958971
TI  - Lateral prefrontal damage affects processing selection but not attention
      switching.
AB  - A challenge for cognitive neuroscience is to determine how the prefrontal cortex
      (PFC) contributes to the cognitive control operations that oversee thought and
      action. We studied the effects of damage to the lateral PFC in two types of
      attentional control. Subjects performed a choice reaction time task that required
      attention switching and processing selection. The performance of individuals with
      PFC or parietal cortex damage was compared with that of age-matched and young
      control subjects. Damage to the lateral PFC did not significantly impair the
      switch from attending to one color to attending to another. PFC damage did,
      however, significantly increase the effects of distractor stimuli, implicating
      the lateral PFC in processing selection. Individual subjects' performance
      suggested that the left inferior posterior PFC was the most critical for
      processing selection. Our data are consistent with the view that the lateral PFC
      contributes to the top-down control of the information flow along pathways from
      sensory input to motor output.

PMID- 11958972
TI  - Brain imaging of human memory systems: between-systems similarities and within
      system differences.
AB  - There is much evidence for the existence of multiple memory systems. However, it
      has been argued that tasks assumed to reflect different memory systems share
      basic processing components and are mediated by overlapping neural systems. Here
      we used multivariate analysis of PET-data to analyze similarities and differences
      in brain activity for multiple tests of working memory, semantic memory, and
      episodic memory. The results from two experiments revealed between-systems
      differences, but also between-systems similarities and within-system differences.
      Specifically, support was obtained for a task-general working-memory network that
      may underlie active maintenance. Premotor and parietal regions were salient
      components of this network. A common network was also identified for two episodic
      tasks, cued recall and recognition, but not for a test of autobiographical
      memory. This network involved regions in right inferior and polar frontal cortex,
      and lateral and medial parietal cortex. Several of these regions were also
      engaged during the working-memory tasks, indicating shared processing for
      episodic and working memory. Fact retrieval and synonym generation were
      associated with increased activity in left inferior frontal and middle temporal
      regions and right cerebellum. This network was also associated with the
      autobiographical task, but not with living/non-living classification, and may
      reflect elaborate retrieval of semantic information. Implications of the present
      results for the classification of memory tasks with respect to systems and/or
      processes are discussed.

PMID- 11958974
TI  - Parallel suspension polymerization for high-throughput resin synthesis.
AB  - A simple, straightforward approach for parallel suspension polymerization is
      described. This technique utilizes equipment common to most organic chemistry
      laboratories and should facilitate the custom synthesis of new polymers.

PMID- 11958975
TI  - Stereoselective synthesis of Psi[CH(2)O] pseudodipeptides and conformational
      analysis of a PhePsi[CH(2)O]Ala containing analogue of the drug desmopressin.
AB  - A method for synthesis of XaaPsi[CH(2)O]Ala/Gly pseudodipeptides in good yields
      and excellent diastereoselectivity from azido alcohols and (R)-2-chloropropionic
      acid or tert-butyl bromoacetate has been developed. Insertion of one of the
      pseudodipeptide building blocks in the peptide drug desmopressin revealed that
      methylene ether isosteres may have only a minor influence on the secondary
      structure of peptides.

PMID- 11958976
TI  - Synthesis of iodinated 3beta-aryltropanes with selective binding to either the
      dopamine or serotonin transporters.
AB  - Iodinated 3beta-aryltropanes functionalized appropriately at the 2beta-, 8- and
      aryl positions display selective binding to either the dopamine or serotonin
      transporters.

PMID- 11958977
TI  - Antibacterial activity of G6-quaternary ammonium derivatives of a lipophilic
      vancomycin analogue.
AB  - A series of G6-amino derivatives of a lipophilic vancomycin analogue was
      prepared. Antibacterial activity of the analogues was inversely proportional to
      the degree of substitution of the G6-nitrogen. The fully substituted (quaternary)
      analogues were essentially inactive against vanA phenotype VREF strains but
      retained substantial activity against other bacteria, a profile reminiscent of
      teicoplanin.

PMID- 11958979
TI  - Synthesis and antibacterial activity of linezolid analogues.
AB  - Several new compounds of oxazolidinone class were designed and synthesized
      referring to the structure-activity relationship studies and the synthesis of
      Linezolid, and their antibacterial activity was studied.

PMID- 11958978
TI  - Synthesis and photochemical protein crosslinking studies of hydrophilic
      naphthalimides.
AB  - A mixture of 4-alkylamino-1,8-naphthalimides has previously been reported to
      exhibit potential utility as a photochemical tissue-bonding reagent. In order to
      determine which constituents of the mixture were responsible for the observed
      tissue bonding and to facilitate study of the mechanism, we have synthesized each
      of the primary constituents of the mixture. Each naphthalimide synthesized has
      been demonstrated to photochemically crosslink proteins.

PMID- 11958981
TI  - Imidazo[5,1-f]triazin-4(3H)-ones, a new class of potent PDE 5 inhibitors.
AB  - 2-aryl-substituted imidazo[5,1-f][1,2,4]triazin-4(3H)-ones represent a new class
      of potent cGMP-PDE 5 inhibitors that prove to be superior to other purine
      isosteric inhibitors. Subnanomolar inhibitors of PDE 5 with activity in in vivo
      models for erectile dysfunction have been identified. BAY 38-9456 (Vardenafil
      hydrochloride) has been selected for clinical studies in the indication of
      erectile dysfunction.

PMID- 11958980
TI  - Antibody-catalyzed cleavage of the D-Ala-D-Lac depsipeptide: an immunological
      approach to the problem of vancomycin resistance.
AB  - Vancomycin resistance is currently a major healthcare problem. The development of
      a catalytic monoclonal antibody (mAb) that hydrolyzes the D-Ala-D-Lac
      depsipeptide provides a potentially novel antibiotic strategy. A phosphonate
      hapten design was used to program antibody catalysis. The characteristics of the
      hapten were shown to be important for obtaining a viable immune response and
      several catalytic mAbs that cleave a peptidoglycan model substrate. The best mAb
      afforded a >500-fold rate enhancement over background.

PMID- 11958982
TI  - Synthesis, characterization and antiamoebic activity of benzimidazole derivatives
      and their vanadium and molybdenum complexes.
AB  - Reaction of [MoO(2)(acac)(2)] (where, acac=acetyl acetone) and KVO(3) with 2
      (salicylidieneimine) benzimidazole lead to form new complexes [MoO(2)(sal
      BMZ)(2)] and K [VO(2)(sal-BMZ)(2)] [where, sal-BMZ=2-(salicylidieneimine)
      benzimidazole], which showed the monobasic bidentate nature of the ligand in
      which the phenolic oxygen and the imine nitrogen of the ligand are coordinated to
      the metal ion. These complexes were characterized along with nine other complexes
      of oxoperoxovanadium (V), molybdenum (Vl) and tungsten (Vl) with benzimidazole
      derivatives and screened in vitro by micro dilution technique for their
      amoebicidal activity with a view to search for a more effective agent against
      Entamoeba histolytica suggests that compound 2 and 3 might be endowed with
      important antiamoebic properties since they showed IC(50 )values in a microM
      range.

PMID- 11958983
TI  - Benzene fused monocyclic enediynyl amides: synthesis, reactivity and DNA-cleavage
      activity in comparison to the corresponding sulfonamides.
AB  - Monocyclic enediynyl amides 2a-2c have been synthesized via the corresponding
      free amine 5. Kinetic studies in chloroform revealed the reactivity of these
      amides towards Bergman cyclization to be less than that of the corresponding
      sulfonamides. However, differential scanning calorimetry (DSC) measurements in
      the solid state and DNA-cleavage studies in aqueous buffer showed higher
      reactivity for the amides than the sulphonamides.

PMID- 11958984
TI  - Dermorphin and deltorphin heptapeptide analogues: replacement of Phe residue by
      Dmp greatly improves opioid receptor affinity and selectivity.
AB  - The usefulness of 2,6-dimethylphenylalanine (Dmp) as a Phe surrogate in two
      opioid peptides, dermorphin (DM) and deltorphin II (DT), was investigated.
      Compared to DM, [L-Dmp(3)]DM (1) showed a 170-fold increase in mu affinity and
      only a 4-fold increase in delta affinity, resulting in a 40-fold improvement in
      mu receptor selectivity. Compared to DT, [L-Dmp(3)]DT (3) showed a 22-fold
      increase in delta affinity and somewhat of a loss in mu affinity, and
      consequently a marked (75-fold) improvement in delta receptor selectivity. The D
      Dmp replacement, however, resulted in a great loss in receptor selectivity in
      each of the peptides. The specific receptor interactions of 1 and 3 were
      confirmed by in vitro bioassays. Analogues 1 and 3 seem to be useful as
      pharmacological tools for the study of opioid systems.

PMID- 11958985
TI  - Tricyclic isoxazoles are novel inhibitors of the multidrug resistance protein
      (MRP1).
AB  - Tricyclic isoxazoles were identified from a screen as a novel class of selective
      multidrug resistance protein (MRP1) inhibitors. From a screen lead, SAR efforts
      resulted in the preparation of LY 402913 (9h), which inhibits MRP1 and reverses
      drug resistance to MRP1 substrates, such as doxorubicin, in HeLa-T5 cells
      (EC(50)=0.90 microM), while showing no inherent cytotoxicity. Additionally, LY
      402913 inhibits ATP-dependent, MRP1-mediated LTC(4) uptake into membrane vesicles
      prepared from the MRP1-overexpressing HeLa-T5 cells (EC(50)=1.8 microM). LY
      402913 also shows selectivity ( approximately 22-fold) against the related
      transporter, P-glycoprotein, in HL60/Adr and HL60/Vinc cells. Finally, when dosed
      in combination with the oncolytic MRP1 substrate vincristine, LY 402913 delays
      the growth of MRP1-overexpressing tumors in vivo.

PMID- 11958987
TI  - Biphenyls as potential mimetics of protein alpha-helix.
AB  - Based on theoretical arguments, 2,6,3',5'-substituted biphenyl analogues are
      proposed as protein alpha-helix mimetics superimposing the side chains of the
      residues i, i+1, i+3 and i+4. Knowing that many protein-protein interactions of
      therapeutical relevance involve alpha-helix contacts, the communication outlines
      how this novel category of scaffolds might potentially open access to such
      targets.

PMID- 11958986
TI  - Chemical synthesis and calcium release activity of N(1)-ether strand substituted
      cADPR mimic.
AB  - 8-Chloro cyclic inosine 5'-diphosphate ethoxymethyl ether 3 was synthesized by
      means of chemical method from protected inosine via phenylthio-type biphosphate
      substrate. The detection of Ca(2+) release activity shows that 3 is a potent
      agonist of cADPR and has activity in intact Hela cells.

PMID- 11958988
TI  - Evaluation of morphogenic regulatory activity of farnesoic acid and its
      derivatives against Candida albicans dimorphism.
AB  - A series of farnesoic acid derivatives was prepared and their morphogenic
      regulatory activities were evaluated. Their inhibitory activities against yeast
      cell growth and yeast-to-hypha transition examined in Candida albicans cells are
      dependent upon the chain length as well as the substitution patterns on the
      isoprenoid template. The preliminary structure-activity relationship of these
      compounds is described to elucidate the essential structural requirements.

PMID- 11958989
TI  - QSAR study on adenosine kinase inhibition of pyrrolo[2,3-d]pyrimidine nucleoside
      analogues using the hansch approach.
AB  - QSAR studies on series of pyrrolo[2,3-d]pyrimidine nucleoside analogues were
      performed for their adenosine kinase (AK) inhibitory activity using the Hansch
      approach. Significant correlations were obtained with hydrophobic parameter at
      position 'X'. Electronic and steric parameters on pyrimidine and pyrrole rings
      found to play an important role in the ligand-receptor interactions with the
      active sites of the enzyme. Presence of bulkier groups at 'X' and 'Y' positions
      seems to protect the title compounds from biodegradation, as is evident from
      their positive sterimol steric parameter B1 at these positions.

PMID- 11958990
TI  - Highly potent inhibitors of TNF-alpha production. Part 1: Discovery of chemical
      leads.
AB  - The discovery of 2-acylamino-2-phenylethyl disodium phosphates and as
      structurally novel inhibitors of TNF-alpha production is reported. Structure
      activity relationships (SARs) are also discussed.

PMID- 11958991
TI  - Highly potent inhibitors of TNF-alpha production. Part 2: identification of drug
      candidates.
AB  - Metabolic stabilization of the chemical lead 1, which is a structurally novel
      inhibitor of TNF-alpha production, was accomplished by introducing a (1S)-methyl
      group into the optically active backbone. As a result, 2, 3 and 4 were identified
      as drug candidates and evaluated pharmacologically. The analysis of an active
      conformer was also carried out.

PMID- 11958992
TI  - Hydrophobic modifications at 1-phosphate of inositol 1,4,5-trisphosphate
      analogues enhance receptor binding.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) analogues were synthesized in order to
      investigate the importance of the environment of 1-phosphate of IP(3) for strong
      binding to the IP(3) receptor. Our results show that hydrophobic modifications of
      the 1-phosphate moiety enhance the binding affinity, with considerable latitude
      of substituent structure.

PMID- 11958993
TI  - Structure-activity study of L-cysteine-based N-type calcium channel blockers:
      optimization of N- and C-terminal substituents.
AB  - Synthesis and structure-activity relationship (SAR) studies of L-cysteine-based N
      type calcium channel blockers are described. In the course of exploring SAR of
      the N- and C-terminal substituents, the L-cysteine derivative was found to be a
      potent N-type calcium channel blocker with an IC(50) value of 0.14 microM on IMR
      32 assay. Compound showed 12-fold selectivity for N-type over L-type calcium
      channels on AtT-20 assay.

PMID- 11958994
TI  - Benzimidazoles and isosteric compounds as potent and selective factor Xa
      inhibitors.
AB  - Benzimidazoles and their isosteric compounds as factor Xa inhibitors are
      discussed.

PMID- 11958995
TI  - Synthesis and evaluation of pseudopeptide analogues of a specific CXCR4
      inhibitor, T140: the insertion of an (E)-alkene dipeptide isostere into the
      betaII'-turn moiety.
AB  - A 14-residue peptide, T140, strongly inhibits the T-cell line-tropic HIV-1 (X4
      HIV-1) infection, since this peptide functions as a specific antagonist against a
      chemokine receptor, CXCR4. T140 takes an antiparallel beta-sheet structure with a
      type II' beta-turn. In the present paper, we have designed and synthesized
      several T140 analogues, in which an (E)-alkene dipeptide isostere was inserted
      into the type II' beta-turn moiety, as a bridging study to develop nonpeptidic
      CXCR4 inhibitors. It has been proven that the turn region of T140 can be replaced
      by the above surrogate with the maintenance of strong anti-HIV activity.

PMID- 11958996
TI  - Probing the overlap of chorismate mutase and prephenate dehydrogenase sites in
      the escherichia coli T-protein: a dehydrogenase-selective inhibitor.
AB  - An inhibitor of prephenate dehydrogenase has been identified that has no effect
      on the chorismate mutase activity in the Escherichia coli T-protein, thus
      supporting the idea of two separate active sites.

PMID- 11958997
TI  - Oxal hydroxamic acid derivatives with inhibitory activity against matrix
      metalloproteinases.
AB  - Several amines, amino acid derivatives and low molecular weight peptides
      containing an amide-bound oxal hydroxamic acid moiety have been synthesized and
      tested for their inhibitory effects towards native human gelatinase B (MMP-9) and
      the catalytic domains of the membrane type MT1-MMP (MMP-14) and of neutrophil
      collagenase (MMP-8). A number of these compounds exhibited considerable
      inhibitory activity against the tested metalloproteinases.

PMID- 11958998
TI  - Identification of a novel, orally bioavailable histamine H(3) receptor antagonist
      based on the 4-benzyl-(1H-imidazol-4-yl) template.
AB  - A novel series of histamine H(3) receptor antagonists, based on the 4-benzyl-(1H
      imidazole-4-yl) template, incorporating urea and carbamate linkers has been
      prepared. Compound 3j is a selective H(3) antagonist and demonstrates excellent
      oral plasma levels in the rat and monkey.

PMID- 11958999
TI  - Oxime derivatives of sordaricin as potent antifungal agents.
AB  - Oxime derivatives of the sordarin aglycone have been identified as potent
      antifungal agents. The in vitro spectrum of activity includes coverage against
      Candida albicans and Candida glabrata with MICs as low as 0.06 microg/mL. The
      antifungal activity was established to be exquisitely sensitive to the spatial
      orientation of the lipophilic side chains.

PMID- 11959001
TI  - Design and synthesis of antiangiogenic/heparin-binding arginine dendrimer
      mimicking the surface of endostatin.
AB  - We designed and synthesized the antiangiogenic arginine-rich dendrimers, TX-1943
      and TX-1944, which mimic the surface structure of endostatin. TX-1944 containing
      16 arginine residues is more similar in surface structure to endostatin than TX
      1943 with eight arginine residues, and has stronger in vivo antiangiogenic
      activity at 10 microg/CAM in the chicken embryo chorioallantoic membrane (CAM)
      assay. TX-1944 also has stronger activity to bind heparin and to inhibit the
      growth of rat lung endothelial (RLE) cells than TX-1943.

PMID- 11959000
TI  - Diaryl-dialkyl-substituted pyrazoles: regioselective synthesis and binding
      affinity for the estrogen receptor.
AB  - We have developed two novel series of tetrasubstituted pyrazoles, embodying 1,3
      diaryl-4,5-dialkyl or 3,5-diaryl-1,4-dialkyl substitution patterns. The scope of
      a regioselective method, developed by us earlier, was expanded to allow the
      synthesis of the first series of these tetrasubstituted pyrazoles directly from
      alpha,beta-unsaturated ketones. The binding affinity of some of these pyrazoles
      for the estrogen receptor (ER) subtypes ERalpha and ERbeta is very high, and the
      overall affinity pattern suggests the importance of three phenol substituents for
      high affinity, ERalpha-selective binding.

PMID- 11959002
TI  - Construction of the novel conformationally-restricted peptide library for
      screening of peptides that control the interaction between nucleobases.
AB  - A unique conformationally-restricted peptide library was constructed using a loop
      structure as a structural scaffold. This library was used for the screening of
      the amino acid sequences that control the interaction between nucleobase
      triplets. The peptides have PNAs at the C-terminus as the recognition site and
      the random amino acid sequence at the N-terminus as the effector for the
      interaction between PNA and its complementary DNA triplets. From the peptide
      libraries constructed by the positional scanning method, the sequences that
      affect the interaction between PNA and complementary DNA were selected. The
      difference in the characteristic results by using A-T and G-C pairs was
      presented. This study would also give us some useful information about
      interaction between peptides and nucleic acids, such as relevances between these
      biomolecules in a prebiotic era.

PMID- 11959003
TI  - Soluble polymer-supported synthesis of benzodiazepinones.
AB  - Soluble polymer-supported synthetic method provides a highly efficient route for
      the construction of biologically important 1,5-benzodiazepin-2-ones. A library of
      N-substituted benzodiazepinones can be readily assembled utilizing S(N)Ar
      reaction, reduction of nitro group and one-pot cyclization following N-alkylation
      as the key step in the synthesis. All reactions in the sequence were performed at
      room temperature to facilitate the generation of libraries in a parallel fashion.
      The crude products were obtained in 80-95% yield with 60-96% HPLC purity.

PMID- 11959005
TI  - Novel N-[1-(1-substituted 4-piperidinylmethyl)-4-piperidinyl]benzamides as potent
      colonic prokinetic agents.
AB  - A series of novel N-[1-(1-substituted 4-piperidinylmethyl)-4
      piperidinyl]benzamides was prepared and its compounds were evaluated for their
      binding to 5-HT(4) receptors and effects on gastrointestinal motility in
      conscious dogs. 4-Amino-N-[1-[1-(4-aminobutyl)-4-piperidinylmethyl]-4
      piperidinyl]-5-chloro-2-methoxybenzamide (15) was found to have a potent binding
      affinity for 5-HT(4) receptors (IC(50): 6.47nM) and showed excellent colonic
      prokinetic activity.

PMID- 11959004
TI  - Formation of thomasidioic acid from dehydrosinapinic acid dilactone under neutral
      conditions, and a remaining inhibitory activity against peroxynitrite-mediated
      protein nitration.
AB  - Dehydrosinapinic acid dilactone (1) was converted to thomasidioic acid (3) and
      (E,E)-2,3-bis(3,5-dimethoxy-4-hydroxybenzylidene)succinic acid (4) via an
      alpha,beta-unsaturated gamma-lactone type dimer (2) in phosphate buffer (pH 7.4).
      A study of the reaction mechanism was accomplished by observing the reaction of
      methyl ester of 2. The lignans (3, 4) were also prevented the peroxynitrite
      mediated protein nitration.

PMID- 11959006
TI  - Design, synthesis and bioactivity evaluation of tribactam beta lactamase
      inhibitors.
AB  - Known carbapenem compounds with inhibitory effect towards beta-lactamase enzymes
      are formed from bicyclical beta lactam structural scaffolds. On the basis of
      results from theoretical computational methods and molecular modelling we have
      designed and developed a synthetic route towards novel, biologically active
      tricyclic derivatives of carbapenems.

PMID- 11959007
TI  - Benzimidazole-4,7-diones as inhibitors of protozoal (Toxoplasma gondii) purine
      nucleoside phosphorylase.
AB  - Benzimidazole-4,7-diones derivatives substituted at 1- and/or 2-position have
      been synthetized and tested as inhibitors of purine nucleoside phosphorylase
      (PNP), isolated from two strains of Toxoplasma gondii (RH and ME 49). They were
      identified as inhibitors of both enzymes.

PMID- 11959008
TI  - Binding properties of oligonucleotides containing a modified 2'-deoxyuridine with
      a thymine ended linker to pair with 2'-deoxyadenosine.
AB  - Oligonucleotides containing in the place of thymidine the nucleoside 2, a 2'
      deoxyuridine harbouring at C-5 a thymine ended linker, were found to undergo base
      pairing with the opposite 2'-deoxyadenosine. However, the corresponding duplexes
      are significantly destabilised as compared to the fully natural ones.

PMID- 11959009
TI  - Bivalent inhibition of beta-tryptase: distance scan of neighboring subunits by
      dibasic inhibitors.
AB  - Based on bifunctional diketopiperazines as templates and m-aminomethyl
      phenylalanine as arginine mimetic, we have synthesized a new class of
      structurally related dibasic tryptase inhibitors with systematically increasing
      spacer length. These compounds were used to scan the distance between the active
      sites of two neighboring subunits of the beta-tryptase tetramer. The K(i)-values
      obtained are a function of the distance between the terminal amino groups and
      indicate optimal binding of inhibitors with 29-31 bonds between the amino groups.
      These experimental data are in full agreement with predictions derived from a
      novel modeling program that allows the docking of bivalent ligands.

PMID- 11959010
TI  - Substrate spectrum of tyrocidine thioesterase probed with randomized peptide N
      acetylcysteamine thioesters.
AB  - Apparent kinetic constants k(cat) and K(m) were determined for tyrocidine
      thioesterase (TycC TE) using randomized peptide N-acetylcysteamine thioesters as
      substrate analogues. The enzyme has been found to be adequately active for the
      synthesis of positional-scanning libraries for novel antibiotic screening with
      reduced k(cat)/K(m) in the range of 2 to 82 folds lower than that of the wild
      type sequence

PMID- 11959012
TI  - Energy metabolism of fish brain.
AB  - This review focuses on recent research on the metabolic function of fish brain.
      Fish brain is isolated from the systemic circulation by a blood-brain barrier
      that allows the transport of glucose, monocarboxylates and amino acids. The
      limited information available in fishes suggests that oxidation of exogenous
      glucose and oxidative phosphorylation provide most of the ATP required for brain
      function in teleosts, whereas oxidation of ketones and amino acids occurs
      preferentially in elasmobranchs. In several agnathans and benthic teleosts brain
      glycogen levels rather than exogenous glucose may be the proximate glucose source
      for oxidation. In situations when glucose is in limited supply, teleost brains
      utilize other fuels such as lactate or ketones. Information on use of lipids and
      amino acids as fuels in fish brain is scarce. The main pathways of brain energy
      metabolism are changed by several effectors. Thus, several parameters of brain
      energy metabolism have been demonstrated to change post-prandially in teleostean
      fishes. The absence of food in teleosts elicits profound changes in brain energy
      metabolism (increased glycogenolysis and use of ketones) in a way similar to that
      demonstrated in mammals though delayed in time. Environmental factors induce
      changes in brain energy parameters in teleosts such as the enhancement of
      glycogenolysis elicited by pollutants, increased capacity for anaerobic
      glycolysis under hypoxia/anoxia or changes in substrate utilization elicited by
      adaptation to cold. Furthermore, several studies demonstrate effects of
      melatonin, insulin, glucagon, GLP-1, cortisol or catecholamines on energy
      parameters of teleost brain, although in most cases the results are quite
      preliminary being difficult to relate the effects of those hormones to
      physiological situations. The few studies performed with the different cell types
      available in the nervous system of fish allow us to hypothesize few functional
      relationships among those cells. Future research perspectives are also outlined.

PMID- 11959013
TI  - Rapid action of cortisol and testosterone on lipogenic enzymes in a fresh water
      fish Oreochromis mossambicus: short-term in vivo and in vitro study.
AB  - Rapid action of steroid hormones on lipid metabolism is not reported so far in
      any vertebrate. The present study was intended to evaluate the quick actions of
      cortisol and testosterone on enzymes, namely malic enzyme (ME), glucose-6
      phosphate dehydrogenase (G6PDH), and isocitrate dehydrogenase (ICDH) in
      Oreochromis mossambicus. Cortisol and testosterone produced rapid and opposite
      effects on the lipogenic enzymes studied. Cortisol significantly decreased the
      activities of ME, G6PDH, as early as 5 min and ICDH as early as 10 min in vitro
      (10(-6) M), and 30 min in vivo (0.1 microg/g body wt.) whereas the same doses of
      testosterone significantly stimulated the activity of all enzymes as early as 5
      min in vitro and 30 min in vivo. Actinomycin D treatment did not interfere with
      the inhibiting effect of cortisol on enzyme activities when measured at 10 min in
      the in vitro system. The transcriptional inhibitor appeared to partially block
      the effect of cortisol in vivo. The stimulatory effect of testosterone was
      insensitive to the action of actinomycin D both in vivo and in vitro. These
      effects appear to be brought about independently of new protein synthesis because
      the rapid responses occurred within a latent period of 5-30 min and were
      insensitive to the action of actinomycin D, suggesting a non-genomic action.

PMID- 11959014
TI  - Cuticular hydrocarbons suggest three lineages in Reticulitermes (Isoptera:
      Rhinotermitidae) from North America.
AB  - Cuticular hydrocarbon mixtures can be used to discriminate insect taxa. They have
      utility for determining phylogenetic relationships where they are independent
      characters with discrete states and represent a hierarchical distribution of
      shared, derived characters. We report inferred degrees of relatedness among the
      chemical phenotypes of Reticulitermes from PAUP (phylogenetic analysis using
      parsimony) analyses of cuticular hydrocarbon characters. One hundred and forty
      one Reticulitermes colonies collected from California, Georgia, New Mexico,
      Arizona and Nevada were used. Initial maximum parsimony analyses sorted the 141
      colonies into 26 chemical phenotypes. Subsequent analyses, using the ancestral
      species Coptotermes formosanus and Heterotermes sp. as outgroups, sorted
      Reticulitermes taxa into three major lineages, each characterized by a different
      set of dominant methyl-branched or unsaturated hydrocarbon components.
      Reticulitermes in lineage I have cuticular hydrocarbon mixtures with a
      preponderance of internally branched monomethylalkanes and 11,15-dimethylalkanes.
      Those in lineage II are defined by a preponderance of 5-methylalkanes and 5,17
      dimethylalkanes. Taxa in lineage III are characterized by the predominance of
      olefins and a relative paucity of n-alkanes and methyl-branched alkanes.
      Bootstrap analyses and decay indices provided statistical support and robustness
      for these chemical-based relationships.

PMID- 11959015
TI  - Seven novel FMRFamide-like neuropeptide sequences from the eyestalk of the giant
      tiger prawn Penaeus monodon.
AB  - FMRFamide-like immunoreactivity (FLI) was localized in the eyestalk of Penaeus
      monodon by immunohistochemistry using a combination of three anti-FMRFamide-like
      peptide (FLPs) monoclonal antibodies. Approximately 3000 small neuronal cell
      bodies in the lamina ganglionalis; 100 medium to large size at the ganglion
      between the medulla interna and the medulla terminalis; and 250 medium size
      around the medulla terminalis were stained intensely. The neuronal processes in
      neuropils of the medulla externa, medulla interna, medulla terminalis, sinus
      gland and some nerve fibers in the optic nerve were also recognized. The small
      cell bodies, approximately 1500 cells, anterior to the medulla externa were
      stained inconsistently and the neuronal processes were not observed from these
      cells. Isolation of FLPs from 9000 eyestalks was performed using
      methanol/acetic/water (90:1:9) extraction. After the extract was partially
      purified using C18 cartridges, it was further purified by five to seven steps of
      RP-HPLC using three kinds of columns: C18; C8; and cyano, and three solvent
      systems: acetonitrile/trifluoro acetic acid; aceonitrile/heptafluoro butyric
      acid; and acetonitrile/triethyl ammonium acetate. Dot-ELISA using the combination
      of the same antibodies was used to monitor FLPs in the fractions during
      purification processes. Seven new sequences of FLPs were identified which can be
      divided into four subgroups according to the primary structure of the C-terminus:
      (1) GDRNFLRFamide; (2) AYSNLNYLRFamide; (3) AQPSMRLRFamide, SQPSMRLRFamide,
      SMPSLRLRFamide and DGRTPALRLRFamide; and (4) GYRKPPFNGSIFamide. These data
      indicate the high complexity of this peptide family in which multiple forms are
      usually exist.

PMID- 11959016
TI  - Immunodissection of yolk lipovitellin (LV1) demonstrates the existence of
      different LV1-domains and suggests a complex family of vitellogenin genes in the
      lizard Anolis pulchellus.
AB  - In the tropical lizard Anolis pulchellus vitellogenin (Vtg), the plasma precursor
      of egg-yolk proteins, consists of a family of five polypeptides ranging between
      116 and 226 kDa. In addition, lipovitellin-LV1, the main yolk protein, resolves
      electrophoretically into several forms. This suggests that yolk LV1 is a mixture
      of similar but distinct peptides that presumably correspond to the LV1 domains of
      the plasma Vtgs. Here, we test the hypothesis that each component of yolk LV1 is
      distinct enough to be antigenically different and that these components
      correspond to cleavage products of plasma Vtg polypeptides. Our experimental
      approach is based on adsorptions of a polyclonal antiserum against purified LV1
      with membrane-immobilized Vtgs. This immunochemical design permitted us to
      dissect sub-populations of LV1 antibodies that specifically reacted with one of
      the plasma Vtgs. The presence of unique epitopes in the LV1 components directly
      indicates differences among the structures of their plasma Vtg precursors and
      supports the idea of a heterogeneous multigene Vtg family in Anolis. These
      results also show the potential of this immunoadsorption approach for the
      identification, and even separation of proteins sharing a high degree of
      similarity in their molecular structures.

PMID- 11959017
TI  - Comparison of the variable loop regions of myosin heavy chain genes from
      Antarctic and temperate isopods.
AB  - The evolutionary adaptations of functional genes to life at low temperatures are
      not well characterised in marine and fresh water invertebrates. Temperature has
      been shown to affect the functional characteristics of fish muscles, with changes
      in the velocity of shortening and ATPase activity being associated with myosin
      heavy chain (MyHC) isoform composition and the structure of the surface loop
      regions. Two PCR products spanning loops 1 and 2 of a MyHC gene from an Antarctic
      isopod (Glyptonotus antarcticus) were sequenced and compared with those of a
      temperate isopod (Idotea resecata), slow and fast fibres from lobster (Homarus
      gammarus) and a cold water amphipod (Eulimnogammarus verrucosus), revealing
      specific differences between the species, possibly related to fibre type and
      habitat temperature. The loop 2 region from G. antarcticus myosin was cloned and
      used for Northern analysis of total RNA from the other species. The cloned myosin
      cDNA hybridised specifically to a 6.6-kb transcript, in G. antarcticus muscle. In
      contrast, cDNA probes for lobster slow myosin and actin hybridised to muscle RNA
      from all species, demonstrating that a distinct MyHC isoform is expressed in the
      Antarctic isopod, as opposed to the temperate species. The inter- and intra
      specific sequence differences in loop 2 region suggest that this may be a site
      for muscle adaptation to enable function at the low temperatures found in the
      Southern Ocean.

PMID- 11959018
TI  - Matrix metalloproteinase-like activity from hemocytes of the eastern oyster,
      Crassostrea virginica.
AB  - Investigation of oyster blood cell lysate revealed one prominent band of
      proteolytic activity when analyzed using gelatin and collagen impregnated
      polyacrylamide gel electrophoresis. The proteolytic activity was inhibited by
      1,10 phenanthroline and EDTA, but not by other proteinase inhibitors. Maximal
      activity was shown at pH 8.2 and the molecular weight of the protein responsible
      for the activity was estimated to be 68 kDa. Proteolytic activity was also
      measured by fluorescence assays containing hemocyte lysate and fluorescein
      labeled gelatin, type I or type IV collagen. Characteristics of this proteolytic
      activity suggest that an invertebrate matrix metalloproteinase is responsible.

PMID- 11959020
TI  - Effect of season on the fatty acid composition and free amino acid content of the
      sardine Sardinops melanostictus.
AB  - The purpose of this study was to clarify the seasonal variation of fatty acid
      composition and free amino acid content in the Japanese sardine (Sardinops
      melanostictus) from the sea of Hyuga-Nada, and the relationship between the fatty
      acid composition of this sardine and that of plankton in the area. The lipid
      content of sardines at the sea of Hyuga-Nada was low in February (1.8%) and high
      (7.2%) from July to September. The major fatty acids in the total lipids from
      sardine were myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0),
      palmitoleic acid (16:1 n-7), oleic acid (18:1 n-9), eicosapentaenoic acid (20:5 n
      3), and docosahexaenoic acid (22:6 n-3). The characteristics of the fatty acids
      isolated from sardines in July were similar to those from plankton in the same
      season. This reflects the deposition of plankton fatty acids in sardine depot
      fat. The season of high free histidine content in the ordinary meat corresponded
      with that of high lipid content. These results suggested that both the fatty acid
      composition of sardines and the high concentrations of certain amino acids in
      free form are influenced by the intake and seasonal variation of composition of
      plankton.

PMID- 11959019
TI  - Mechanism of biosynthesis of trimethylamine oxide from choline in the teleost
      tilapia, Oreochromis niloticus, under freshwater conditions.
AB  - The mechanism of biosynthesis of trimethylamine oxide (TMAO) from dietary
      precursors in the teleost tilapia (Oreochromis niloticus) was investigated. Diets
      supplemented with quaternary ammonium choline, glycine betaine, carnitine or
      phosphatidylcholine were administered and significant increases in TMAO levels in
      the muscle were only observed with choline. [Methyl-14C] and [1,2-14C] cholines
      were given through dietary and intraperitoneal injection routes, but 14C-TMAO was
      detected only in fish with dietary administration of [methyl-14C] choline.
      Dietary treatment with [15N] choline resulted in the formation of [15N] TMAO in
      the muscle. The incorporation of radioactivity into TMAO was also observed both
      following dietary administration and intraperitoneal injection of [14C]
      trimethylamine (TMA). When choline was introduced into the isolated intestine,
      marked increases in TMA levels occurred. These increases were significantly
      suppressed in the presence of penicillin. [14C]-TMA derived from [methyl-14C]
      choline was detected in the cavity of the isolated intestine. The introduction of
      [15N] choline into the intestinal cavity resulted in the formation of [15N] TMA.
      TMA mono-oxygenase activities were detected in the liver and kidney. We conclude
      that tilapia possess the ability to produce TMAO from choline, which is related
      to intestinal microorganisms and tissue mono-oxygenase under freshwater
      conditions.

PMID- 11959021
TI  - Lipids and fatty acids in muscle, liver and skin of three edible fish from the
      Senegalese coast: Sardinella maderensis, Sardinella aurita and Cephalopholis
      taeniops.
AB  - Lipid content and fatty acid composition were determined in three species of
      edible fish caught in Senegalese waters during the upwelling season (January,
      1993). Sardinella maderensis and Sardinella aurita are fat fish containing more
      than 5% (fresh wt.) of lipids, whereas Cephalopholis taeniops is a lean fish with
      approximately 1% of lipids. Skin, liver and muscle were studied for each fish
      species. About 40 fatty acids were identified by GC and GC/MS as methyl esters
      and N-acyl pyrrolidides. Palmitic acid was the main acid in the muscle and skin
      of all samples studied (20-33% of total fatty acids). Oleic acid was the main
      fatty acid in the liver of S. maderensis (27.2%+/-0.1) and S. aurita (44.7%+/
      0.1). Arachidonic acid was a minor component in all samples. The flesh (muscle)
      of the three fish species contained high concentrations of omega3 polyunsaturated
      fatty acids (PUFA), ranging from 16.0 to 29.1% and including 20:5 omega3
      (eicosapentaenoic acid, EPA) and 22:6 omega3 (docosahexaenoic acid, DHA) acids as
      major components. These two acids together accounted for 24.7%+/-0.1 and 12.9%+/
      0.1 of total acids in the skin of S. maderensis and S. aurita, respectively. The
      percentages of PUFA found in the fish studied were very similar to those in fish
      used commercially as sources of PUFA. Muscle sterols, which accounted for 9-11%
      of total lipids, consisted mainly of cholesterol (up to 97% of total sterols).

PMID- 11959022
TI  - Oxidative stress during vitamin A-induced abnormal tail regeneration in the
      tadpoles of Polypedates maculatus.
AB  - Vitamin A and its derivatives inhibit normal tail regeneration in amphibians. The
      most remarkable effect is the development of limbs at the cut end of the tail in
      anurans. Prior to ectopic limb development, there is an abnormal tail
      regeneration in the treated tadpoles. The purpose of the present study was to
      compare oxidative stress condition in the regenerated tail of normal and vitamin
      A (10I U/ml, 72 h) treated tadpoles. The present findings show a hyper-oxidative
      stress condition in the regenerated tail of the vitamin A-treated tadpoles of the
      Indian jumping frog, Polypedates maculatus (Anura: Rhacophoridae).

PMID- 11959023
TI  - Glyceraldehyde-3-phosphate dehydrogenase from the newt Pleurodeles waltl. Protein
      purification and characterization of a GapC gene.
AB  - The NAD(+)-dependent cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPDH,
      EC 1.2.1.12) has been purified to homogeneity from skeletal muscle of the newt
      Pleurodeles waltl (Amphibia, Urodela). The purification procedure including
      ammonium sulfate fractionation followed by Blue Sepharose CL-6B chromatography
      resulted in a 24-fold increase in specific activity and a final yield of
      approximately 46%. The native protein exhibited an apparent molecular weight of
      approximately 146 kDa with absolute specificity for NAD(+). Only one GAPDH
      isoform (pI 7.57) was obtained by chromatofocusing. The enzyme is an
      homotetrameric protein composed of identical subunits with an apparent molecular
      weight of approximately 37 kDa. Monospecific polyclonal antibodies raised in
      rabbits against the purified newt GAPDH immunostained a single 37-kDa GAPDH band
      in extracts from different tissues blotted onto nitrocellulose. A 510-bp cDNA
      fragment that corresponds to an internal region of a GapC gene was obtained by RT
      PCR amplification using degenerate primers. The deduced amino acid sequence has
      been used to establish the phylogenetic relationships of the Pleurodeles enzyme-
      the first GAPDH from an amphibian of the Caudata group studied so far--with other
      GAPDHs of major vertebrate phyla.

PMID- 11959024
TI  - A functional comparison of ovine and porcine trypsins.
AB  - Trypsin was isolated from ovine and porcine pancreas using affinity
      chromatography on immobilized p-aminobenzamidine. Molecular masses of the two
      proteins were 23900 and 23435 Da, determined by matrix-assisted laser
      desorption/ionisation time of flight (MALDI-TOF) mass spectrometry. The purified
      trypsins were compared using the kinetic properties K(m) and k(cat) which were
      determined at pH 8.0 and between 25 and 55 degrees C. Comparison of the Michaelis
      constants for ovine and porcine trypsins toward N-alpha-benzoyl-arginine-p
      nitroanilide (BapNA) indicated that ovine trypsin had higher affinity for this
      substrate than the porcine enzyme. The rates of the reactions catalysed by the
      two enzymes correlated strongly over the range of temperatures and substrate
      concentrations tested, as did the k(cat) values. The specific activity of ovine
      trypsin for BapNA was, on average, approximately 10% higher than that of the
      porcine enzyme over the range of conditions tested. Porcine trypsin was less
      susceptible to denaturation at low pH or high temperature than was ovine trypsin.
      Porcine and ovine trypsin produced seven identically sized fragments from auto
      catalytic hydrolysis. Proposed regions of identity between ovine and porcine
      trypsins were I(54)-K(77), L(98)-R(107), S(134)-K(178) and N(209)-K(116).
      Hydrolysis of beta-lactoglobulin, egg white lysozyme or casein by ovine or
      porcine trypsin yielded virtually identical patterns of fragments although the
      rate at which fragments were produced, in the case of beta-lactoglobulin,
      differed between the two enzymes. On balance the two enzymes appear to be
      functionally identical in their action.

PMID- 11959025
TI  - Occurrence and tissue distribution of c-series gangliosides in the common squid
      Todarodes pacificus.
AB  - We have recently demonstrated that the common squid Todarodes pacificus express
      acidic lipids that were reactive with a monoclonal antibody A2B5. In the present
      study, two A2B5-reactive acidic lipids were isolated from squid hepatopancreatic
      tissue and characterized for their structures by methods including glycolipid
      overlay analysis, product analysis after sialidase treatment, and electrospray
      ionization-mass spectrometry (ESI-MS). Accordingly, the two acidic lipid were
      identified as GT3 and GQ1c, respectively. Another A2B5-reactive acidic lipid in
      the tissue was tentatively assigned to GT2 based upon its reactivity to A2B5 and
      chromatographic mobility on thin-layer chromatography. The composition and
      concentration of c-series gangliosides significantly differed among squid tissues
      (i.e. hepatopancreas, cerebral ganglion, eye lens, and mantle tissue).
      Interestingly, the percentages of c-series gangliosides within total gangliosides
      of hepatopancreas and cerebral ganglion were even higher than that of cod fish
      brain, which is known to be highly enriched with this ganglioside species. These
      findings strongly support the hypothesis that c-series gangliosides in squid
      tissues are not derived from ganglioside-containing food intake, but
      biosynthesized in a tissue-specific manner.

PMID- 11959026
TI  - Differential expression of glutathione S-transferase isoenzymes in murine small
      intestine and colon.
AB  - Glutathione (GSH) S-transferase (GST) isoenzymes of the small intestine and colon
      of female A/J mice have been purified and characterized to determine their
      interrelationships with other murine GSTs. Cytosolic GST activity in the small
      intestine was at least due to six isoenzymes with isoelectric points (pI) of 9.5,
      9.3, 9.1, 8.5, 6.2 and 5.5. Small intestine isoenzymes with pI values of 9.5,
      9.3, 8.5, and 6.2 were identical to the mGSTA1-1 (Alpha class), mGSTP1-1 (Pi
      class), mGSTM1-1 (Mu class) and mGSTA4-4 (Alpha class), respectively, of other
      A/J mouse tissues on the basis of their reverse-phase HPLC elution profile,
      immunological cross-reactivity and/or N-terminal region amino acid sequence. Even
      though GST9.1 of the small intestine cross-reacted with the antibodies raised
      against Pi class GST, reverse-phase HPLC and N-terminal amino acid sequence
      analyses suggested that this isoenzyme may be structurally different from mGSTP1
      1 as well as mGSTP2-2. Likewise, despite immunological similarity with the Mu
      class GSTs, small intestine GST5.5 appeared to be different from other Mu class
      murine GSTs characterized previously. Cytosolic GST activity in the colon was
      mainly due to four isoenzymes with pI values of 9.8, 9.4, 6.6 and 5.8. While the
      identity of colon GST6.6 could not be established due to its low abundance,
      GST9.8, GST9.4 and GST5.8 were identical to mGSTP1-1, mGSTM1-1 and mGSTA4-4,
      respectively, of other A/J mouse tissues including the small intestine.
      Isoenzymes corresponding to small intestine GST9.1 and GST5.5 could not be
      detected in the colon. The results of the present study indicate that the small
      intestine of female A/J mice is better equipped for protection against toxic
      effects of electrophiles than colon.

PMID- 11959027
TI  - Partial characterization of trypsin-like protease and molecular cloning of a
      trypsin-like precursor cDNA in salivary glands of Lygus lineolaris.
AB  - Based on substrate specificity, an alkaline pH optimum, sensitivity to selected
      proteinase inhibitors, and molecular analysis, we provide evidence for the
      presence of a trypsin-like serine proteinase in the salivary gland complex (SGC)
      of the tarnished plant bug, Lygus lineolaris (Palisot de Beauvois) (Heteroptera:
      Miridae). The predominant activity in extracts of the SGC against N(2)-benzoyl-L
      arginine-p-nitroanilide (L-BApNA) was at pH 10, but a minor peak of activity also
      occurred at pH 5. The major BApNAase activity focused at 10.4 during preparative
      isoelectric focusing and was eluted with an apparent molecular weight of 23,000
      from a calibrated gel filtration column. The BApNAase fraction gave a single
      major band when analyzed on a casein zymogram. The activity was completely
      suppressed by the serine protease inhibitors, phenylmethylsulfonyl fluoride
      (PMSF) and lima bean trypsin inhibitor. A cDNA coding for a trypsin-like protein
      in the salivary glands of L. lineolaris was cloned and sequenced. The 971bp cDNA
      contained an 873-nucleotide open reading frame encoding a 291-amino acid trypsin
      precursor. The encoded protein included amino acid sequence motifs that are
      conserved with four homologous serine proteases from other insects. Typical
      features of the putative trypsin-like protein from L. lineolaris included the
      serine protease active site (His(89), Asp(139), Ser(229)), conserved cysteine
      residues for disulfide bridges, the residues (Asp(223), Gly(252), Gly(262)) that
      determine trypsin specificity, and both zymogen signal and activation peptides.
      Cloning and sequencing of a trypsin-like precursor cDNA provided additional
      direct evidence for trypsin like enzymes in the salivary glands of L. lineolaris.

PMID- 11959029
TI  - Substantial species differences in relation to formation and degradation of N
      acyl-ethanolamine phospholipids in heart tissue: an enzyme activity study.
AB  - The formation of N-acyl-ethanolamines (NAEs), including the cannabinoid receptor
      ligand anandamide, and their precursors N-acyl-ethanolamine phospholipids (NAPEs)
      are catalyzed by NAPE-hydrolyzing phospholipase D (NAPE-PLD) and N-acyl
      transferase, respectively. NAPE and NAE are suggested to have beneficial effects
      on the heart, but in the literature there are indications of species differences
      in the activity of these enzymes. We have examined heart microsomes from rats,
      mice, guinea pigs, rabbits, frogs, cows, dogs, cats, mini pigs and human beings
      for activities of these two enzymes. N-Acyl-transferase activity was very high in
      dogs and cats (>13 pmol/min/mg protein) whereas it was very low to barely
      detectable in the other species (<3 pmol/min/mg protein). NAPE-PLD activity was
      very high in rats and guinea pigs (>45 pmol/min/mg protein) whereas it was 9
      pmol/min/mg protein in frogs and below that in the other species. The ratio of
      activity between the two enzymes varied from 0.002 to 15 in the investigated
      species. The activity of the two enzymes in rat hearts as opposed to rat brain
      did not change during development. These results indicate that there may be
      substantial species differences in the generation of anandamide and other NAEs as
      well as NAPEs in heart tissues.

PMID- 11959028
TI  - Dolichol phosphate mannose synthase is differentially expressed in male and
      female worms of Schistosoma mansoni.
AB  - The cDNA encoding the Schistosoma mansoni dolichol phosphate mannose synthase was
      completely sequenced, displaying the highest homology with Cricetulus griseus and
      Saccharomyces pombe genes. The Schistosome enzyme had a K(m) of 0.127 microM, a
      value that is within the range of those reported for several other species. Thin
      layer chromatography of the radiolabelled schistosome lipid intermediate showed
      it was identical to dolichol-phosphate (C80-C105). Expression of dolichol
      phosphate mannose synthase of S. mansoni (SmDPMS) was analysed by Northern blot
      and quantified by semi-quantitative RT-PCR with cDNA from mature and immature
      male and female worms. Northern blot analysis revealed a single 1-kb band. Both
      approaches confirmed a higher level of expression in mature female worms, as
      compared to immature and male worms.

PMID- 11959030
TI  - Canine mitochondrial uncoupling proteins: structure and mRNA expression of three
      isoforms in adult beagles.
AB  - Uncoupling proteins (UCPs) are members of the mitochondrial transporter family
      that dissipate the proton gradient as heat more than via ATP synthesis. In the
      present study, nucleotide and amino acid sequences of UCPs 1, 2 and 3 of a dog
      were determined, and their mRNA expression in various peripheral tissues was
      examined. The sequences were highly (76-97%) homologous to those of other
      species. Although lower homologies (60-74%) were found when compared among the
      three canine UCPs, their deduced amino acid sequences had some common domains,
      such as three mitochondrial carrier protein motifs, six transmembrane alpha-helix
      domains, and putative purine nucleotide binding domains. By Northern blot
      analyses, UCP1 mRNA was not detected in any tissues examined. UCP2 mRNA was
      expressed in most tissues, particularly abundantly in adipose tissue, spleen and
      lung. Two sizes of UCP3 mRNA were found exclusively in heart and skeletal muscle.
      These results suggest that canine UCPs have uncoupling activity, and are involved
      in the regulation of metabolic heat production and/or energy expenditure, as do
      those of other species.

PMID- 11959031
TI  - Comparative study of the effects of short- and long-term ethanol treatment and
      alcohol withdrawal on phospholipid biosynthesis in rat hepatocytes.
AB  - This study describes the effects of short- and long-term ethanol treatment and
      withdrawal on the biosynthesis of the phospholipids phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE) in hepatocytes isolated from rats, using
      isotopically labelled choline and ethanolamine as exogenous precursors. Our
      results demonstrate that short-term ethanol consumption increases the
      incorporation of exogenous polar bases into PC and PE, whereas long-term ethanol
      administration provokes a differential effect in both PC and PE biosynthesis via
      cytidine diphosphate derivatives (CDP-derivatives), decreasing PC synthesis and
      increasing the biosynthesis of PE. We suggest that the increased biosynthesis of
      PE after ethanol treatment results from changes in lipogenic substrates produced
      as a consequence of ethanol metabolism, whilst the specific inhibition of PC
      biosynthesis seems to be a consequence of alterations of enzymes involved in the
      CDP-choline pathway. With regard to the influence of ethanol on PE methylation to
      give PC, our results demonstrate that ethanol activates this pathway in short
      term, as well as chronic ethanol treatment. Ethanol withdrawal returns the
      activity of the PC and PE pathways to control levels. The alterations in the
      biosynthesis of the main phospholipids, PC and PE, demonstrated in this study
      could be of a great physiological interest in determining the pathology of
      alcoholism.

PMID- 11959033
TI  - Purification and partial characterization of camel (Camelus Dromedarius)
      ceruloplasmin.
AB  - Adult and young camel ceruloplasmin (Cp) were isolated and purified using the
      single-step chromatography on amino ethyl-activated sepharose. There are no
      differences between the adult and the young camel protein. The molecular mass of
      the protein, as estimated by SDS-PAGE (denaturant conditions), was approximately
      130000 Da. The electrophoretic mobility of camel Cp is slightly higher as
      compared to human and sheep protein suggesting that the camel Cp is homogeneous,
      compact and more acid. The copper content was estimated to be 5.8+/-0.3 atoms per
      molecule. The spectroscopic feature includes an absorption maximum at 610 nm,
      which could be attributed to type 1 copper. The EPR spectrum was completely
      devoid of any typical signal of the type 2 copper. The kinetic parameters of the
      adult camel Cp for the specific activity as p-phenylendiamine oxidase were
      determined as K(m)=0.42 mM and V(max)=0.93 microM NADH/mn/mg Cp. The optimum pH
      for the activity was 5.7.

PMID- 11959032
TI  - Kazal-type chymotrypsin inhibitor from duck pancreas.
AB  - A chymotrypsin inhibitor of the Kazal-type has been isolated from duck pancreas,
      by affinity chromatography on immobilized chymotrypsin, gel filtration on Bio-Gel
      P-10 and reverse phase (RP)-HPLC. It inhibits bovine chymotrypsin Aalpha with an
      association constant (K(a)) of 2.06x10(7) M(-1). The complete amino acid sequence
      was determined after digestion of pyridylethylated inhibitor with Staphylococcus
      aureus V8 protease and chemical cleavage with CNBr. Duck pancreatic chymotrypsin
      inhibitor (DPCI) was found to be a single polypeptide chain composed of 65 amino
      acid residues, corresponding to a molecular mass of 7191 Da.

PMID- 11959034
TI  - Deoxyribonuclease II purified from Euglena gracilis SM-ZK, a chloroplast-lacking
      mutant: comparison with porcine spleen deoxyribonuclease II.
AB  - An acid deoxyribonuclease was extracted from Euglena gracilis SM-ZK, a
      chloroplast-lacking strain, by homogenizing the cells in 50 mM sodium acetate (pH
      4.6). The enzyme was then purified by heat treatment and a series of
      chromatographic separations. The molecular mass of the Euglena acid DNase was
      estimated to be 45 kDa by sensitive activity staining in an SDS-polyacrylamide
      gel using SYBR Green. Treatment of the Euglena enzyme with a reducing agent prior
      to electrophoresis destroyed its DNase activity in the gel, indicating that
      disulfide bridging is essential for its enzyme activity. Nucleolytic properties
      of this enzyme are essentially the same as to those of porcine DNase II. The
      Euglena enzyme acts on both double-stranded (ds) and single-stranded DNA, but
      acts preferentially on dsDNA with an optimum pH at approximately 5.3. EDTA did
      not inhibit its enzyme activity. Euglena DNase makes double-strand breaks in
      circular DNA substrate and generates a terminus with 3'-phosphate and 5'-OH.
      These results indicate that the Euglena acid DNase is in fact a member of the
      DNase II family.

PMID- 11959035
TI  - Ontogeny of erythropoietin mRNA expression in liver, kidneys and testes of the
      foetal and the neonatal pig.
AB  - Erythropoietin (EPO) mRNA expression in kidneys, liver and testes of foetal and
      neonatal pigs was analysed using a competitive RT-PCR assay. The results indicate
      that in the foetal pig, erythropoietin expression is greatest in the liver, at
      birth; hepatic and renal expression are nearly identical, and by 5 weeks of age
      there is mainly renal expression. The dynamics of the renal expression of EPO
      mRNA in the perinatal period provide a correlate for observations made earlier of
      plasma EPO concentrations. Early in foetal life (30 days after artificial
      insemination), the mesonephroi contained large amounts of EPO mRNA. As in the
      rat, the testes produced EPO mRNA in amounts comparable to the liver on a per
      gram tissue basis, though much less on a per organ basis.

PMID- 11959037
TI  - Lipids and sterols in Musca domestica L. (Diptera, Muscidae): changes after
      treatment with sucrose and lead.
AB  - Total lipid, fatty acid and sterol composition of larvae and adults of Musca
      domestica was investigated before and after feeding on sucrose syrup or on the
      same syrup containing 1% lead nitrate. The effects of sucrose and of lead ions
      were found to be different. In larvae sucrose diet inhibited the fatty acid
      elongation and stimulated the first stages of their unsaturation. A significant
      increase of phytosterol concentrations was obtained. These changes increased the
      cell membrane permeability. The addition of lead caused a decrease of the fatty
      acid unsaturation, which decreased the cell membrane permeability. In adults the
      sucrose diet had no effect on the lipid and sterol composition, while the
      addition of lead decreased the cholesterol concentration. The composition of
      lipids and sterols also depends on the diet of larvae before pupation. The data
      obtained suggested that changes in lipid and sterol composition, which control
      the permeability of the cell membrane, might be an adaptive response of the
      organism to the changes of the environment.

PMID- 11959036
TI  - Effects of carnosine on bilharzial infestation in hamsters: biochemical and
      histochemical studies.
AB  - We tested the ability of carnosine to improve some liver disorders induced by
      Schistosoma mansoni parasite in hamsters (Mesocricetus auratus). Results indicate
      that parasitic infestation induced elevation in serum alkaline phosphatase, gamma
      glutamyl transferase, aspartate aminotransferase and procollagen III peptide as a
      marker of liver fibrosis. Administration of carnosine (10 mg/day) for 15 days
      either concurrent with infection, 2 and 4 weeks post-infestation was effective in
      reducing differential worm burden. It was also effective in renormalizing blood
      glucose level depending on the time course. The most evident effect of carnosine
      was on serum procollagen III peptide level, which was lowered in infested groups
      treated with carnosine. Histopathological studies confirmed the potential use of
      carnosine for intervention in schistosomiasis.

PMID- 11959038
TI  - Glycosaminoglycan-degrading enzymes in the skin of fasted rats.
AB  - During fasting of animals, there is decreased content of skin glycosaminoglycans
      (GAGs) accompanied by decrease in their biosynthesis. Since tissue GAG content
      depends on both synthesis and degradation of these molecules, we asked whether
      fasting affects the activity of several tissue glycosidases. Therefore we
      measured the activity of skin neutral and acidic endoglycosidases, some
      exoglycosidases: beta-N-acetylhexosaminidase [EC 3.2.1.30], beta-galactosidase
      [EC 2.1.23], beta-glucuronidase [EC 3.2.1.31], alpha-iduronidase [EC 3.2.1.76],
      and two sulfatases: arylsulfatase B [EC 3.1.6.1] and 6-sulfatase [EC 3.1.6.14] in
      the skin of control and fasted rats. Although fasting was accompanied by distinct
      decrease in the activity of most neutral endoglycosidases, no characteristic
      changes in the activity of exoglycosidases were found. In contrast, we found that
      fasting is associated with increase in the activity of acidic endoglycosidases
      (of lysosomal origin) which degraded hyaluronic acid, chondroitin-4-sulfate,
      chondroitin-6-sulfate and heparin. The same GAGs were decreased in the skin of
      fasted rats. Our data suggest that the phenomenon is a result of increased
      intracellular degradation of these molecules. Therefore, not only decreased
      biosynthesis of GAGs during fasting, but also increased their intracellular
      degradation may contribute to decrease in GAG skin content.

PMID- 11959039
TI  - Influence of progressive renal dysfunction in chronic heart failure.
AB  - Chronic heart failure (CHF) is often associated with impaired renal function due
      to hypoperfusion. Such patients are very sensitive to changes in renal perfusion
      pressure, and may develop acute tubular necrosis if the pressure falls too far.
      The situation is complicated by the use of diuretics, ACE inhibitors and
      spironolactone, all of which may affect renal function and potassium balance.
      Chronic renal failure (CRF) may also be associated with fluid overload. Anaemia
      and hypertension in CRF contribute to the development of left ventricular
      hypertrophy (LVH), which carries a poor prognosis, so correction of these factors
      is important.

PMID- 11959040
TI  - Angiotensin II subtype 1 (AT1) receptors contribute to ischemic contracture and
      regulate chemomechanical energy transduction in isolated transgenic rat (alphaMHC
      hAT1)594-17 hearts.
AB  - BACKGROUND: The role of AT1 receptors in myocardial ischemia/reperfusion injury
      is unclear. We, therefore, investigated the effects of the AT1 receptor
      antagonist irbesartan (Irb) in isolated hearts of selective myocardial AT1
      overexpressing transgenic [transgenic(alphaMHC-hAT1)594-17] and Sprague-Dawley
      rats (SD) subjected to ischemia/reperfusion injury. METHODS AND RESULTS: Hearts
      of 4-week-old male SD or transgenic rats were isolated and perfused with Krebs
      Henseleit buffer with or without 10 microM Irb in Langendorff mode. After 15 min
      of stabilization, pressure-volume curves were obtained and the hearts subjected
      to 20 min ischemia followed by 30 min reperfusion. A second set of pressure
      volume curves was obtained thereafter. Left ventricular developed pressure
      (LVDP), end-diastolic pressure (LVEDP), total coronary flow (CF) and oxygen
      consumption (MVO2) were recorded continuously. Myocardial efficiency was derived
      from the slope of relations of MVO2 to pressure/volume area. After 20 min
      ischemia, LVEDP was significantly higher in transgenic than in SD (35.7+/-1.8 vs.
      29.2+/-1.0 mmHg, P<0.05) or Irb treated transgenic hearts (24.3+/-1.6 mmHg,
      P<0.05). Myocardial efficiency was increased by Irb before ischemia. Ischemia
      increased efficiency in SD but not in transgenic rats, Irb increased efficiency
      in transgenic hearts post-ischemia. CONCLUSION: Transgenic hearts developed
      ischemic contracture more rapidly than SD hearts as indicated by higher LVEDP
      during ischemia. This response was antagonized by Irb, indicating a role of AT1
      receptors in ischemic contracture, AT1-receptors also appear to be involved in
      the control of myocardial efficiency.

PMID- 11959041
TI  - Increased myocardial expression of osteopontin in patients with advanced heart
      failure.
AB  - The expression of the adhesion protein osteopontin (OP) is associated with
      cardiac hypertrophy and is significantly increased after transition to heart
      failure in experimental animal models. We, therefore, hypothesized that OP could
      be upregulated in heart failure in humans. In the present study, we investigated
      the expression of OP in myocardial biopsies obtained from patients with heart
      failure due to dilated cardiomyopathy (mean LVEF=30.3+/-4.4%, mean+/-S.D., n=10,
      group A) compared to patients with a normal left-ventricular ejection fraction
      (mean LVEF=61+/-11.2%, n=9; group B). Myocardial immunoreactivity for OP was
      examined using two different antibodies against OP. The expression of cardiac
      myocyte OP was significantly upregulated in group A in comparison to group B
      (P<0.0001). Both groups also displayed OP immunoreactivity in non-myocytes,
      including vascular smooth muscle cells and cardiac fibroblasts (P=not
      significant). Statistical analysis revealed a significant correlation of
      increased OP immunoreactivity in cardiac myocytes of patients with impaired left
      ventricular function, assessed by hemodynamic data (LVEF, RVEF, LVESVI, LVEDVI
      and LVEDP, R=-0.828, -0.671, 0.751, 0.685 and 0.461, respectively; all P<0.05).
      Furthermore, OP expression correlated with cardiac myocyte hypertrophy (mean
      diameter 21.0+/-1.8 microm in group A and 16.6+/-2.1 microm in group B;
      P<0.0001). In conclusion, the present study indicates, that factors and/or
      mechanisms involved in heart failure in patients with dilated cardiomyopathy,
      lead to induction of OP expression in humans.

PMID- 11959042
TI  - Unique effects of carvedilol on noradrenaline release in the human heart.

PMID- 11959043
TI  - Fractal correlation properties of R-R interval dynamics in asymptomatic relatives
      of patients with dilated cardiomyopathy.
AB  - BACKGROUND AND AIM: asymptomatic relatives of patients with familial dilated
      cardiomyopathy who have left ventricular enlargement [LVE] are at risk for
      progression to dilated cardiomyopathy. A novel index of the fractal correlation
      properties of heart rate variability (HRV), the short-term scaling component
      (proportional, variant(1)) in detrended fluctuation analysis, is a promising
      prognostic tool in left ventricular dysfunction. The aim of this study was to
      compare values of proportional, variant(1) and conventional HRV indices in LVE
      relatives with dilated cardiomyopathy patients and normal controls. METHODS: time
      domain and spectral HRV measures, and the short-term scaling component (
      proportional, variant(1)) were assessed from 24-h Holter recordings from 22 LVE
      relatives (left ventricular end-diastolic dimension >112% predicted, normal
      fractional shortening), 24 dilated cardiomyopathy patients and 14 controls.
      RESULTS: the time domain index SDNN was lower in dilated cardiomyopathy patients
      [101.8(+/-44.0)] than in LVE relatives [161.7(+/-53.9)] or controls [152.9(+/
      51.4)], P=0.01. Similarly, triangular index and spectral measures were reduced in
      dilated cardiomyopathy patients but not in LVE relatives or controls. In
      contrast, the short term scaling component ( proportional, variant(1)) in
      detrended fluctuation analysis was reduced in both dilated cardiomyopathy
      patients [1.06(+/-0.33)] and in LVE relatives [1.15 (+/-0.20)], compared with
      controls [1.32(+/-0.16)], P=0.01. Among DCM patients the short-term scaling
      component ( proportional, variant(1)) was significantly associated with
      echocardiographic deterioration during follow-up (3.7+/-2.1 year) (P=0.004).
      CONCLUSION: the short-term scaling component ( proportional, variant(1)) is
      reduced in asymptomatic relatives of dilated cardiomyopathy patients who have
      LVE.

PMID- 11959044
TI  - Recovery of cardiac autonomic responsiveness with low-intensity physical training
      in patients with chronic heart failure.
AB  - BACKGROUND: A gradual worsening of autonomic control of cardiovascular function
      accompanies the progression of heart failure. Exercise training modulates
      autonomic balance, and may affect the prognosis of the disease. AIMS: The
      sympathovagal balance was studied after 3 months of low-intensity rehabilitation
      compared with conventional therapy in 45 patients with heart failure (52%
      ischemic, 48% idiopathic), of whom 30 underwent rehabilitation and 15 did not. In
      11 rehabilitated patients we also studied the effects on autonomic profile of 6
      additional months of home-based training. Rehabilitated and non-rehabilitated
      patients had similar NYHA class, ejection fraction, exercise pVO2; 50% assumed
      carvedilol (39+/-5 mg/day). METHODS AND RESULTS: Autoregressive power spectral
      density of RR intervals variability were assessed during 10 min of: (1) supine
      rest and free breathing; (2) supine rest and breathing at 20 acts/min (=vagal
      stimulus); (3) standing (=sympathetic stimulus). During each period, the ratio
      LF/HF of the individual autospectrum indicated the sympathovagal balance. After 3
      months of rehabilitation, pVO2 increased (20%); LF/HF at rest was unchanged
      (8.7+/-1.2 vs. 9.2+/-1.2); it decreased with controlled breathing (-18%) and
      increased during standing (+79%) (P<0.05). These changes were more evident after
      6 months of home-based training, when pVO2 was still high: LF/HF at rest was
      reduced (5.4+/-0.9 vs. 8.5+/-2.1), decreased during controlled breathing (-17%)
      and increased during standing (87%) (P<0.05). No changes in any variable were
      seen in non-rehabilitated patients. CONCLUSIONS: A low intensity rehabilitation
      program restores autonomic tone and reactivity to vagal and sympathetic stimuli.
      Some of these effects are already evident after the initial hospital-based phase.

PMID- 11959045
TI  - Hypomagnesemia and concurrent acid-base and electrolyte abnormalities in patients
      with congestive heart failure.
AB  - BACKGROUND: Patients with severe decompensated congestive heart failure (CHF)
      commonly exhibit acid-base and electrolyte disturbances mainly due to the
      activation of several neurohumoral mechanisms as well as to drugs regularly used
      in this population. Magnesium deficit is not infrequently observed in CHF
      patients but its pathophysiology remains less well-studied as compared with other
      electrolyte alterations, such as hypokalemia. However, there is evidence that
      early detection and correction of magnesium abnormalities could obviate
      potentially deleterious arrhythmogenic effects. AIM: To assess the incidence of
      magnesium level disorders and analyze the underlying pathophysiological
      mechanisms in patients with CHF. METHODS: Eighty-six consecutive CHF patients
      (NYHA class III or IV) admitted to our hospital over a period of 5 years were
      studied. Patients with diabetes mellitus, liver or renal failure, and chronic
      obstructive lung disease were excluded. All patients received conventional
      treatment with digoxin, diuretic agents and an angiotensin converting enzyme
      inhibitor. On admission, blood and urine electrolytes and renal function
      parameters were determined. Arterial blood gases and serum anion gap
      determinations were also performed. RESULTS: Hypomagnesemia was found in 15 [n=15
      (17.4%)] CHF patients. The majority of these patients also exhibited other
      electrolyte abnormalities, such as hypokalemia, hypocalcemia and
      hypophosphatemia. Inappropriate magnesiuria (fractional excretion of magnesium
      >4%) was evident in eight hypomagnesemic patients. A variety of associated
      conditions, including poor dietary intake, also favored magnesium depletion.
      CONCLUSION: Magnesium deficit is a common electrolyte disorder in CHF (NYHA class
      III/IV) patients and several interrelated mechanisms are implicated in its
      pathogenesis. Clinicians' awareness of the incidence of hypomagnesemia in this
      population as well as its related pathophysiology could be useful for the early
      detection and appropriate treatment to inhibit its arrhythmogenic potential.

PMID- 11959047
TI  - Glucose insulin potassium infusion improves systolic function in patients with
      chronic ischemic cardiomyopathy.
AB  - OBJECTIVE: We assessed the effects of glucose-insulin-potassium (GIK) by
      echocardiography in stable patients with ischemic dysfunction. METHODS: Twelve
      male patients with stable coronary disease (SCD) and ejection fraction (EF) <45%
      were studied for systolic function. GIK (glucose 30%, 300 insulin units and KCl 6
      g/l) was infused at 1 ml/kg per h over 20 min. Hemodynamic and echocardiographic
      measurements were recorded at rest (T(0)), at the end (20 min) of GIK infusion
      (T+20), 20 and 40 min after the end of the infusion (T+40 and T+60). RESULTS: At
      T+20, a significant decrease in WMSI (wall motion score index) was observed
      compared with T(0) (2.16+/-0.14 vs. 2.30+/-0.16: P<0.05). An increase in EF was
      reported at T+40 and T+60 compared with T(0) (44.1+/-7.8% and 53.3+/-11.6% vs.
      35.6+/-4.5%, respectively: P<0.01). A decrease in WMSI was observed at T+40 and
      T+60 compared with rest (2.02+/-0.17 and 1.93+/-0.11 vs. 2.30+/-0.16,
      respectively: P<0.01). CONCLUSION: Our present work suggests that GIK infusion
      improves systolic function in patients with SCD and ejection fraction <45%.
      Further studies are needed to determine if short-term GIK infusion could be
      useful for therapeutic or diagnostic strategies in these patients.

PMID- 11959046
TI  - Lactic acidosis following heart transplantation: a common phenomenon?
AB  - BACKGROUND: Lactic acidosis (LAc) is a common form of metabolic acidosis early
      after heart transplantation (HTX). The mechanism remains unclear. This study
      analyzed 13 patients who developed severe LAc after HTX. METHODS: From a series
      of 60 consecutive heart transplant patients, we identified 13 patients with LAc
      in the first hours following HTX. Nine patients with normal or mildly elevated
      lactate levels (<5.0 mmol/l) were investigated as controls. RESULTS: Thirteen
      patients developed a moderate or severe LAc (up to 14.6 mmol/l) after HTX. Serum
      lactate levels increased immediately following surgery with a peak after 6.3+/
      1.4 h, spontaneously returning to normal values within 24 h. In contrast to the
      control group, a significant correlation was found between the maximal serum
      lactate level and the maximal dosage of inotropic drugs (r=0.93, P<0.02),
      administered during the reperfusion phase and continued for 12-24 h
      postoperatively. No correlation was found between LAc and blood gas analysis
      during extracorporeal perfusion period. CONCLUSION: LAc can occur after HTX and
      seems to be related to the inotropic support of the graft. In contrast to other
      forms, LAc after HTX has an excellent prognosis and resolves rapidly and
      spontaneously without treatment. The fact that inotropic support during and
      immediately after cardiac transplantation can enhance preexisting severe
      peripheral metabolic cellular dysfunction remains hypothetical.

PMID- 11959048
TI  - GH-independent cardiotropic activities of hexarelin in patients with severe left
      ventricular dysfunction due to dilated and ischemic cardiomyopathy.
AB  - AIM: To investigate acute cardiotropic activities of hexarelin in patients with
      severe left ventricular dysfunction due to ischemic (iCMP) and dilated
      cardiomyopathy (dCMP). METHODS AND RESULTS: We studied the effect of intravenous
      hexarelin administration on growth hormone (GH) levels and left ventricular
      ejection fraction (LVEF) evaluated by radionuclide angiography in eight patients
      with dCMP (age 53.0+/-2.8, LVEF 16.7+/-2.1%) and five patients with iCMP (age
      52.0+/-2.8 years, LVEF 22.6+/-2.1). Results were compared with a group of seven
      normal subjects (age 37.4+/-3.4 years, LVEF 64.0+/-1.5%) and seven patients with
      severe growth-hormone deficiency (GHD; age 42.0+/-4.4 years, LVEF 50.0+/-1.9%)
      previously studied with the same methodology. In dCMP and iCMP patients hexarelin
      induced a similar significant (P<0.05) increase in GH levels. In iCMP patients
      hexarelin induced a LVEF increase (peak LVEF 26.2+/-2.5%, P<0.05) as observed in
      normals and GHD, while in dCMP LVEF was unchanged (peak LVEF 17.7+/-1.7, P=NS).
      In all groups other hemodynamic parameters were unchanged. CONCLUSIONS: Acute
      hexarelin administration increases LVEF in iCMP patients (as in normals and GHD)
      but not in dCMP patients in spite of a similar GH releasing effect and basal
      LVEF. A possible explanation of the positive inotropic effect of hexarelin in
      iCMP could be a direct stimulation on viable myocardium or myocardial contractile
      reserve.

PMID- 11959049
TI  - Addition of candesartan to angiotensin converting enzyme inhibitor therapy in
      patients with chronic heart failure does not reduce levels of oxidative stress.
AB  - BACKGROUND: Angiotensin II exerts a number of harmful effects in patients with
      chronic heart failure (CHF) and, through an increase in oxidative stress, is
      thought to be critical in the development of endothelial dysfunction. Angiotensin
      II may be elevated in CHF despite treatment with angiotensin converting enzyme
      (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor
      blockade. We investigated whether the addition of angiotensin antagonism to ACE
      inhibition would reduce oxidative stress and improve endothelial function and
      exercise tolerance in patients with chronic heart failure. METHODS AND RESULTS:
      Twenty-eight heart failure patients, who were on stable ACE inhibitor therapy,
      were randomised to receive adjunctive therapy with candesartan or placebo. Plasma
      lipid-derived free radicals, TBARS and neutrophil O2-generation, markers of
      oxidative stress, were measured in venous blood. Arterial endothelial function
      was assessed as the response of the brachial artery to flow-related shear stress.
      Exercise capacity was determined by cardiopulmonary exercise testing. Compared
      with placebo, candesartan had no effect on changes in lipid derived free radicals
      (-0.1+/-1.2 vs. -0.1+/-1.0 units, respectively, P=NS), TBARS (-2.2+/-1.1 vs. 
      2.6+/-2.2 micromol/l, respectively, P=NS) or neutrophil O2-generating capacity (
      7.3+/-5.1 vs. -8.4+/-7.9 mV/5x10(5) neutrophils, respectively, P=NS). There was
      no effect on changes in brachial artery flow-mediated dilatation (0.5+/-1.0 vs.
      0.8+/-1.3%, respectively, P=NS) nor peak VO2 (1.6+/-0.7 ml/kg per min vs. 1.8+/
      0.6 ml/kg per min; P=NS). CONCLUSION: The addition of the candesartan to ACE
      inhibitor therapy had no effect on oxidative stress and did not improve
      endothelial function or exercise capacity in patients with CHF.

PMID- 11959050
TI  - Effect of dofetilide on QT dispersion and the prognostic implications of changes
      in QT dispersion for patients with congestive heart failure.
AB  - AIMS: Drug-induced changes in QT dispersion may be a way of detecting harmful
      repolarisation abnormalities for patients receiving antiarrhythmic drugs
      affecting ventricular repolarisation. METHODS AND RESULTS: In 463 congestive
      heart failure (CHF) patients enrolled in the Danish Investigations Of Arrhythmia
      and Mortality On Dofetilide-CHF (DIAMOND-CHF) study, both pre-treatment and on
      treatment day 2-6 QT dispersion was available from standard 12-lead ECGs.
      Patients were randomised in a double-blind manner to receive either placebo or
      dofetilide, a new class III antiarrhythmic drug. During a median follow-up of 19
      months (minimum 1 year), 179 patients (39%) died (135 patients from cardiac
      causes). Changes in QT dispersion did not predict all-cause or cardiac mortality
      for patients treated with dofetilide in multivariate survival analysis (Risk
      ratio: 1.02, 95% confidence interval: 0.97-1.08, P>0.4). This finding was
      independent of pre-treatment QT dispersion. Dofetilide caused a small QT
      dispersion increment of 8 ms, not different from the changes seen in the placebo
      group (3 ms). CONCLUSION: For patients with CHF and reduced left ventricular
      systolic function, changes in QT dispersion following treatment with dofetilide
      do not predict all-cause or cardiac mortality. The dofetilide-induced QT
      dispersion changes are small and comparable to those seen in placebo treated
      patients.

PMID- 11959051
TI  - Therapeutic options and heart failure survival score predictability in an
      academic heart failure center: an analysis of 120 consecutive patients during a 1
      year period.
AB  - BACKGROUND: the incidence and prevalence of patients with advanced heart failure
      is increasing worldwide and the number of cardiac transplantations remains
      limited. AIMS: it was the aim of the study to describe our experience with the
      increasing number of available medical, interventional and cardiac surgery
      options, and to assess heart failure survival score predictability in an academic
      heart failure center within a 1-year follow-up. METHODS AND RESULTS: in all
      patients who were referred for cardiac transplant evaluation within a 12-month
      period between April 1998 and March 1999 at our Interdisciplinary Heart Failure
      and Transplant Program, our team assessed all medical interventions as well as
      interventional and surgical treatment options that were available, based on the
      clinical profile on initial presentation. In 92% of the 120 patients referred for
      cardiac transplantation evaluation, drug therapy could be optimized. A
      considerable number of patients could be subjected to an organ-preserving
      intervention or surgery, either PTCA (n=11), CABG (n=4), valve repair (n=7),
      multisite pacing (n=7), or partial ventricular resection (n=5). Only a small
      group of patients with the worst heart failure survival score were listed for
      heart transplantation (n=17) or received a ventricular assist device (n=3).
      CONCLUSIONS: within a contemporary cohort of advanced heart failure patients,
      only a small number of patients will undergo cardiac transplantation, which is
      predictable by the heart failure survival score. Most patients will undergo
      optimized medical therapy and a considerable number will be subjected to
      interventional or surgical treatment options.

PMID- 11959052
TI  - Management of heart failure patients in Poland.
AB  - Over the next 10 years, heart failure is likely to become a medical and
      sociological problem as a result of improved treatment of ischaemic heart disease
      and hypertension. At present, in Poland, there are only 50% of the cardiological
      or cardiac surgery procedures (coronarography, PTCA, CABG, surgery of congenital
      or acquired heart disease) performed compared to Western Europe. After being
      registered on the waiting list, it can take anything between 3 and 12 months
      before the procedure is done. Patients with heart failure have diagnostic tests
      such as ECG, chest X-ray, and biochemical evaluation performed regardless of the
      level of care. When echocardiography, exercise testing or Holter monitoring is
      required, it is done at specialist or reference specialist facilities with a
      waiting time of approximately 1-3 months. Pharmaceutical treatment of CHF is also
      inadequate. ACE inhibitors are prescribed in approximately 68% of patients. The
      average prescribed dosage is far from that recommended in guidelines. Only 18-29%
      of patients with HF are on beta blockers. The improvement of cardiological care
      standards depends mainly on the financial resources of State Health System
      Agencies.

PMID- 11959053
TI  - Utility of history, physical examination, electrocardiogram, and chest radiograph
      for differentiating normal from decreased systolic function in patients with
      heart failure.
AB  - To determine whether clinical parameters alone can differentiate normal versus
      decreased systolic left ventricular function in patients with heart failure.
      Detailed clinical data were collected prospectively from 225 consecutive patients
      who were hospitalized with heart failure. Findings in patients with normal
      (ejection fraction > or =45%) or decreased (ejection fraction <45%) left
      ventricular function were compared. Systolic function was normal in 104 patients
      (46%) and decreased in 121 patients (54%). Patients with normal function were
      older (mean [+/- SD] age, 59 +/- 13 years vs. 54 +/- 13 years, P = 0.007) and
      more likely to be female (56% vs. 35%, P = 0.001), obese (body mass index > or
      =30 kg/m(2), 62% vs. 48%, P = 0.04), have marked systolic (> or =160 mm Hg, 50%
      vs. 27%, P <0.001) and diastolic (> or =110 mm Hg, 25% vs. 13%, P = 0.02)
      hypertension, and use calcium antagonists (34% vs. 14%, P = 0.001). Patients with
      decreased function were more likely to use alcohol (37% vs. 20%, P = 0.007),
      angiotensin-converting enzyme (ACE) inhibitors (85% vs. 62%, P <0.001), and
      digoxin (57% vs. 27%, P <0.001); and more likely to have tachycardia (51% vs.
      32%, P = 0.004), rales (89% vs. 80%, P = 0.05), electrocardiographic left
      ventricular hypertrophy (42% vs. 22%, P = 0.002), left atrial abnormality (52%
      vs. 22%, P <0.001), or flow cephalization on chest radiograph (91% vs. 79%, P =
      0.02). Only sex, tachycardia, and use of digoxin and ACE inhibitors were
      associated with ventricular function in multivariable analysis. However, the
      sensitivity, specificity, and predictive values for all clinical variables were
      low. Differences in clinical parameters in heart failure patients with decreased
      versus normal systolic function cannot predict systolic function in these
      patients, supporting recommendations that heart failure patients should undergo
      specialized testing to measure ventricular function.

PMID- 11959054
TI  - Association of forced expiratory volume with disease duration and sputum
      neutrophils in chronic asthma.
AB  - Some patients with chronic asthma develop irreversible airflow obstruction. Our
      aim was to assess whether reported duration of asthma and induced sputum cell
      counts were associated with pulmonary function in patients with asthma who did
      not smoke. Maximal forced expiratory volume in the first second (FEV(1)) was
      determined following a steroid trial (oral prednisolone, 30 mg/d [n = 92
      patients]; or inhaled fluticasone, 2000 microg/d [n = 5]; for 2 weeks) and 2.5 mg
      of nebulized albuterol. Asthma history was recorded with duration from first
      diagnosis. All subjects were nonsmokers, or were to have stopped smoking > or =5
      years previously and smoked < or =5 pack-years (n = 12). Induced sputum was
      obtained from 59 subjects for analysis of airway cell counts. Maximal FEV(1) was
      inversely associated with asthma duration (r = -0.47, P <0.0001), age (r = -0.40,
      P <0.0001), and the proportion of sputum neutrophils (r(s) = -0.50, P = 0.00004).
      After adjusting for age, both duration of disease and sputum neutrophils were
      independently associated with maximal FEV(1). Neutrophil activation, as measured
      by sputum myeloperoxidase levels, was positively associated with the proportion
      of sputum neutrophils (r(s) = 0.45, P = 0.0004) and inversely associated with
      maximal FEV(1) (r(s) = -0.59, P <0.0001). Long disease duration may be a
      predisposing factor for the development of irreversible airflow obstruction in
      patients with chronic asthma. The negative associations of sputum neutrophil
      count and activation with maximal FEV(1) suggest that neutrophils may be involved
      in the pathophysiology of irreversible airflow obstruction in asthma.

PMID- 11959055
TI  - The prognostic value of exercise testing in elderly men.
AB  - PURPOSE: Our purposes were to compare the responses to exercise testing in
      elderly (> or =65 years of age) and younger men, and to investigate whether
      exercise testing has similar prognostic value in the two age groups. METHODS: We
      included all elderly (n = 1185) and younger (n = 2789) male veterans without
      established coronary heart disease who underwent routine clinical exercise
      testing between 1987 and 2000 at two academically affiliated Veteran's Affairs
      medical center laboratories. Measurements included a standardized medical
      history, exercise testing, and all-cause mortality. RESULTS: Compared with
      younger patients, elderly patients achieved a lower workload (a mean [+/- SD] of
      7 +/- 3 vs. 10 +/- 4 metabolic equivalents [METs], P <0.001) and were more likely
      to have abnormal ST depression (27% [n = 324] vs. 16% [n = 436], P <0.001).
      During the mean follow-up of 6 years, annual mortality was twice as high among
      elderly patients as among younger patients (4% vs. 2%, P <0.001). The only
      exercise test variable that was associated significantly with time to death in
      both age groups was maximal METs achieved: each 1 MET increase in exercise
      capacity was associated with an 11% reduction in annual mortality. Exercise
      induced ST depression was more common in those who subsequently died, but was not
      an independent predictor of mortality. CONCLUSION: In elderly men, exercise
      testing provided prognostic information incremental to clinical data. Achieved
      workload (in METs) was the major exercise testing variable associated with all
      cause mortality. Its prognostic importance was the same in elderly as in younger
      men.

PMID- 11959056
TI  - Nonchemotherapy drug-induced agranulocytosis in elderly patients: the effects of
      granulocyte colony-stimulating factor.
AB  - PURPOSE: Elderly patients with nonchemotherapy drug-induced agranulocytosis
      present commonly with severe infections, and have a mortality of at least 20%. We
      studied whether granulocyte colony-stimulating factor (G-CSF), a hematopoietic
      growth factor that shortens the duration of neutropenia, is useful in these
      patients. SUBJECTS AND METHODS: We studied 54 patients > or =65 years of age who
      had drug-induced agranulocytosis, some of whom had been treated with G-CSF. We
      determined the times until hematologic recovery (defined as a neutrophil count
      >1.5 x 10(9)/L), tolerance of G-CSF, and clinical outcomes. RESULTS: Of the 54
      patients, 20 received G-CSF. Two patients who had not been treated with G-CSF
      died of uncontrolled septic shock and extensive pneumonia. The mean (+/- SD) time
      until hematologic recovery was significantly less in patients treated with G-CSF
      (6.6 +/- 3.9 days vs. 8.8 +/- 4.9 days, P <0.04). Compliance with G-CSF therapy
      was good; only mild flu-like symptoms and transient bone pain were reported in 12
      patients. CONCLUSION: Our findings suggest that G-CSF therapy may be beneficial
      in the management of drug-induced agranulocytosis in elderly patients.

PMID- 11959057
TI  - Cigarette smoking and the risk of rheumatoid arthritis among postmenopausal
      women: results from the Iowa Women's Health Study.
AB  - PURPOSE: To determine whether cigarette smoking increases the risk of rheumatoid
      arthritis among postmenopausal women. SUBJECTS AND METHODS: We followed a cohort
      of 31 336 women in Iowa who were aged 55 to 69 years in 1986 and who had no
      history of rheumatoid arthritis. Through 1997, 158 cases of rheumatoid arthritis
      were identified and validated based on review of medical records and
      supplementary information provided by physicians. Multivariable Cox proportional
      hazards regression was used to derive rate ratios (RRs) and 95% confidence
      intervals (CIs) for the association between cigarette smoking and rheumatoid
      arthritis. RESULTS: Compared with women who had never smoked, women who were
      current smokers (RR = 2.0; 95% CI: 1.3 to 2.9) or who had quit 10 years or less
      before study baseline (RR = 1.8; 95% CI: 1.1 to 3.1) were at increased risk of
      rheumatoid arthritis, but women who had quit more than 10 years before baseline
      were not at increased risk (RR = 0.9; 95% CI: 0.5 to 2.6). Both the duration and
      intensity of smoking were associated with rheumatoid arthritis. Multivariable
      adjustments for age, marital status, occupation, body mass index, age at
      menopause, oral contraceptive use, hormone replacement therapy, alcohol use, and
      coffee consumption did not alter these results. CONCLUSION: These results suggest
      that abstinence from smoking may reduce the risk of rheumatoid arthritis among
      postmenopausal women.

PMID- 11959059
TI  - Is there an association between hypertension and cancer mortality?
AB  - BACKGROUND: Because of suggestions that hypertension may increase the long-term
      risk of cancer, we assessed the relation between hypertension and malignancy.
      METHODS: We conducted a MEDLINE search of English-language articles published
      between January 1966 and January 2000 using the terms hypertension or blood
      pressure, and neoplasm or cancer or malignancy. We reviewed prospective studies
      that reported cancer incidence or mortality in hypertensive and nonhypertensive
      patients, case-control studies that reported the prevalence of hypertension in
      cancer patients and controls, and references from identified articles. RESULTS:
      We identified 10 longitudinal studies that evaluated the association between
      blood pressure and cancer mortality in 47 119 subjects. Subjects with
      hypertension experienced an increased rate of cancer mortality during durations
      of follow-up ranging 9 to 20 years, with an age- and smoking-adjusted pooled odds
      ratio of 1.23 (95% confidence interval [CI]: 1.11 to 1.36). In 13 case-control
      studies, including 6964 cases of renal cell cancer and 9181 controls, the
      adjusted odds ratio for renal cell cancer among hypertensive patients, relative
      to normotensive counterparts, was 1.75 (95% CI: 1.61 to 1.90). No clear
      association was found between hypertension and cancer of other sites. CONCLUSION:
      Hypertension was associated with an increased risk of mortality from cancer,
      particularly renal cell carcinoma.

PMID- 11959058
TI  - Is "quality of care" being mislabeled or mismeasured?
AB  - According to Francis Peabody, "The secret of the care of the patient is in caring
      for the patient." This secret has been well guarded in current approaches to
      measuring "quality of care." The measurements have concentrated on performance of
      approved technical procedures, such as the appropriate ordering of diagnostic
      tests, pharmaceutical agents, or surgery, but have generally ignored traditional
      components of caring, such as relieving pain or other symptoms, improving
      functional capacity, and assuaging anxiety or distress. By ordering the pertinent
      technical procedures, a health care system, institution, or clinician can get
      excellent ratings for "quality of care," despite gross violations of human
      caring. Although offering desirable assurance that the best procedures are being
      used, the current measurements need a more accurate label, such as "quality of
      technical performance." If the process of caring is to be emphasized and
      appraised appropriately, new methods will be required. They can be developed to
      identify specific activities in caring and perhaps to include evaluations of
      accomplishment for what patients say they want done.

PMID- 11959060
TI  - Musculoskeletal disorders of the hand and shoulder in patients with diabetes
      mellitus.

PMID- 11959061
TI  - Nonspecific interstitial pneumonitis as the sole histologic expression of
      hypersensitivity pneumonitis.

PMID- 11959062
TI  - Cases from the Osler Medical Service at Johns Hopkins University. Diagnosis:
      Polymorphic population of mature and immature hematopoietic cells consistent with
      extramedullary hematopoiesis.

PMID- 11959063
TI  - Can clinical evaluation differentiate diastolic from systolic heart failure? If
      so, is it important?

PMID- 11959064
TI  - A role for neutrophils in asthma?

PMID- 11959066
TI  - Alvan Feinstein: A tribute to quality and caring.

PMID- 11959067
TI  - "We're jinxed"--are residents' fears of being jinxed during an on-call day
      founded?

PMID- 11959068
TI  - Rhabdomyolysis with acute renal failure probably related to the interaction of
      atorvastatin and delavirdine.

PMID- 11959069
TI  - Primary mucosa-associated lymphoid tissue lymphoma of the gallbladder.

PMID- 11959070
TI  - Cancer risk and Barrett's esophagus.

PMID- 11959071
TI  - Hypertensive crisis associated with St. John's Wort.

PMID- 11959072
TI  - Telogen effluvium as a clinical presentation of human immunodeficiency virus
      infection.

PMID- 11959073
TI  - Balint's syndrome-missed or mistaken?

PMID- 11959074
TI  - Interaction between ritonavir and statins.

PMID- 11959076
TI  - Quinolones and stroke in the elderly.

PMID- 11959077
TI  - Community-based teaching: defining the added value for students and preceptors.

PMID- 11959079
TI  - Society of Biological Psychiatry 57th Annual Convention. May 16-18, 2002.
      Philadelphia, Pennsylvania, USA. Abstracts.

PMID- 11959082
TI  - Inhibition of T-type Ca(2+) currents in mouse spermatogenic cells by gossypol, an
      antifertility compound.
AB  - Gossypol, a male antifertility compound isolated from cotton, has been proved to
      inhibit capacitation and the acrosome reaction in human and mammalian sperm.
      Here, by using whole-cell recording, we observed the effects of gossypol on
      Ca(2+) and Cl(-) currents in mouse spermatogenic cells obtained by mechanical
      dissociation. The results showed that gossypol concentration-dependently and
      irreversibly inhibited T-type Ca(2+) currents in the cells. When the
      concentration of gossypol was > or =5 microM, the currents were blocked
      completely. The time to current block was progressively shortened as the gossypol
      concentration was increased from 5 to 80 microM. Moreover, the drug increased the
      time constant of inactivation in a concentration-dependent manner, while it did
      not affect the activation of the current. The inhibitory effect on the T-type
      Ca(2+) current did not correlate with signaling mediated by G proteins and
      tyrosine phosphorylation. No obvious effect of gossypol on Cl(-) currents was
      observed. These data suggest that the gossypol-induced inhibition of T-type
      Ca(2+) currents could be responsible for the antifertility activity of the
      compound, indicating a possibility to use gossypol as a local contraceptive drug.

PMID- 11959083
TI  - The influence of P-glycoprotein on morphine transport in Caco-2 cells. Comparison
      with paclitaxel.
AB  - In vitro monolayer studies using Caco-2 cells were employed here to explore P
      glycoprotein mediated transport of morphine. Bi-directional transport studies of
      10-75 microM morphine showed efflux to be twofold higher than influx (4 x 10(-6)
      compared to 2 x 10(-6) cm/s) and cellular accumulation in the efflux direction
      was eightfold higher. The cyclosporin analogue (PSC-833) equilibrated morphine
      transport in both directions. Depletion of intracellular glutathione had a
      greater effect on increasing cellular morphine accumulation than P-glycoprotein
      inhibitors, suggesting a role for glutathione in morphine transport. P
      glycoprotein had a substantially greater effect on paclitaxel accumulation,
      efflux and bi-directional transport than for morphine. Paclitaxel transport was
      below detection (<0.1 x 10(-6) cm/s) in the influx direction, yet efflux was very
      high (18.4 x 10(-6) cm/s) and P-glycoprotein inhibition increased accumulation
      >100-fold. These results reinforce the substantial role P-glycoprotein has in
      paclitaxel transport. Conversely, P-glycoprotein regulated morphine transport is
      weak. Nevertheless, morphine transport rates could be doubled when administered
      with P-glycoprotein substrates. Therefore, increased analgesia through P
      glycoprotein inhibition should be possible.

PMID- 11959085
TI  - Antidepressant activity of memory-enhancing drugs in the reduction of submissive
      behavior model.
AB  - The present study tests the activity of nootropic drugs in a behavioral test
      linked to depression. This test measures the reduction of submissive behavior in
      a competition test as the relative success of two food-restricted rats to gain
      access to a feeder. Nootropic drugs tested include piracetam (2-oxo-1
      pyrrolidineacetamide), aniracetam (1-(4-methoxybenzoyl)-2-pyrrolidinone), the
      Ampakine, Ampalex, 1-(quinoxalin-6-ylcarbonyl)piperidine, and analogs were
      compared to the antidepressants, fluoxetine ((+/-)-N-methyl-gamma-(4
      [trifluoromethyl]phenoxy)-benzenepropanamine) and desimpramine (5H
      dibenz[b,f]azepine-5-propanamine, 10,11-dihydro-N-methyl-, monohydrochloride),
      while the anxiolytic diazepam (7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin
      2(1H)-one) served as a control. Drugs were given intraperitoneally for 3 weeks.
      The antidepressant and nootropic drugs reduced submissive behavior over time. The
      effect was dose dependent as measured for fluoxetine and Ampakines. The reduction
      of submissive behavior by Ampakines gradually faded after cessation of treatment
      and had a more rapid onset of activity (during the 1st week of treatment) than
      fluoxetine (after 2 weeks). The results suggest that Ampakines may have
      antidepressant activity. The potential of depression treatment with memory
      enhancing drugs is hypothesized and the link between cognition and depression is
      discussed.

PMID- 11959084
TI  - Recombinant GABA(B) receptors formed from GABA(B1) and GABA(B2) subunits
      selectively inhibit N-type Ca(2+) channels in NG108-15 cells.
AB  - Efficient transfection of NG108-15 cells with GABA(B) receptor subunits was
      achieved using polyethylenimine. Baclofen modulated high voltage-activated Ca(2+)
      current in differentiated cells transfected with GABA(B1) and GABA(B2) receptor
      subunits or with the GABA(B2) subunit alone, but not with the GABA(B1) subunit
      alone. Characteristics of the current modulation were very similar for cells
      transfected with GABA(B1/2) and GABA(B2) subunits. Using antisense
      oligonucleotides against GABA(B1) subunits and also western immunoblotting, we
      are able to show that NG108-15 cells contain endogenous GABA(B1) subunits.
      Therefore, functional receptors can be formed by the combination of native
      GABA(B1) subunits with transfected GABA(B2) subunits, in agreement with the
      proposed heteromeric structure of GABA(B) receptors. Finally, we used selective
      channel blockers to identify the subtypes of Ca(2+) channels that are modulated
      by GABA(B) receptors. In fact, in differentiated NG108-15 cells, the recombinant
      GABA(B) receptors couple only to N-type Ca(2+) channels.

PMID- 11959086
TI  - Peripheral 5-HT(2A)-receptor-mediated formation of an inhibitor of atrial
      natriuretic peptide binding involves inflammation.
AB  - A peripheral 5-HT(2A) receptor-mediated hemodynamic change prompted formation of
      indole-2,3-dione, an endogenous inhibitor of atrial natriuretic peptide (ANP)
      receptor binding and G protein-mediated intracellular signaling (IC(50): 0.4
      microM). This effect was significantly suppressed by dexamethasone, indomethacin
      and the 5-HT(2) receptor antagonists, ketanserin or ritanserin. 5-HT(2A) receptor
      mediated acute hemodynamic change was not modified significantly by indomethacin,
      prazosin or propranolol pretreatment. A tyrosine hydroxylase inhibitor, alpha
      methyl-p-tyrosine, but not a dopamine beta hydroxylase inhibitor,
      diethyldithiocarbamate, abolished the 5-HT(2A) receptor-mediated increase in
      indole-2,3-dione. Exogenous indole-2,3-dione induced a significant increase in
      plasma catecholamine levels and decrease in urine volume. A 5-HT(2A) receptor
      mediated decrease in capillary flow may have caused an inflammatory process and
      peripheral sympathetic activation via ANP signaling inhibition. 3,4
      dihydroxyphenylalanine (DOPA)/dopamine may contribute to the progression of
      inflammation or the generation of a precursor of indole-2,3-dione. The
      observation that indole-2,3-dione abolished angiotensin AT(1) receptor-mediated
      NADPH activation in both human umbilical vein endothelial cells and smooth muscle
      cells at 20 microM may suggest that sulfhydryl-reactive indole-2,3-dione could
      influence mitochondrial function and cellular redox states via flavoenzyme
      inhibition and/or regulation of dehydrogenase-oxidase conversion.

PMID- 11959087
TI  - Sildenafil and T-1032, phosphodiesterase type 5 inhibitors, showed a different
      vasorelaxant property in the isolated rat aorta.
AB  - The vasorelaxant effects of sildenafil and T-1032 [methyl-2-(4-aminophenyl)-1,2
      dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline
      carboxylate sulfate], two phosphodiesterase type 5 inhibitors, were examined in
      the isolated rat aorta. Sildenafil and T-1032, both of which have almost the same
      potency and selectivity regarding phosphodiesterase type 5 inhibitory activity,
      produced a similar, moderate, relaxation at 10(-10) to 10(-7) M (sildenafil: 66.8
      +/- 13.7%; T-1032: 77.9 +/- 10.8% at 10(-7) M). However, sildenafil, but not T
      1032, produced further relaxation at the higher concentrations (sildenafil: 102.0
      +/- 0.6%; T-1032: 81.0 +/- 7.2% at 10(-4) M, P < 0.05). Sildenafil also produced
      a more potent relaxation than did T-1032 at the high concentrations (10(-5) and
      10(-4) M) in endothelium-denuded aortic rings and in the presence of N(G)-nitro-L
      arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor (3 x 10(-4) M).
      Moreover, the high concentrations of sildenafil, but not of T-1032, caused a
      rightward shift of the concentration-response curve for calcium chloride in K(+)
      depolarized endothelium-denuded preparations. In the ligand binding assay for the
      L-type Ca(2+) channels, the affinities of sildenafil at 10(-5) M for binding
      sites of nitrendipine and (--)-desmethoxyverapamil [(--)- D888] (35.2 +/- 3.3%
      and 35.8 +/- 1.9%, respectively) were higher than those of T-1032 (11.8 +/- 4.0%
      and -13.1 +/- 1.3%, respectively, P < 0.05). Regarding cyclic nucleotide levels,
      both phosphodiesterase type 5 inhibitors increased cGMP levels at 10(-6) M.
      However, sildenafil, but not T-1032, further increased cGMP levels at the higher
      concentrations (sildenafil: 15.7 +/- 2.7 pmol/mg protein; T-1032: 5.6 +/- 0.6
      pmol/mg protein at 10(-4) M, P < 0.05). These results suggested that high
      concentrations of sildenafil had additional vasorelaxant properties through
      mechanisms other than phosphodiesterase type 5 inhibition. Sildenafil-induced
      relaxation appears to be due to inhibition of the external Ca(2+)-dependent
      cascade for contraction and/or to an increase in cGMP levels. In contrast, T-1032
      only showed a vasorelaxant property due to phosphodiesterase type 5 inhibition.
      In conclusion, T-1032 appears to be a specific phosphodiesterase type 5 inhibitor
      compared with sildenafil and a useful compound to examine the physiological
      function of phosphodiesterase type 5.

PMID- 11959088
TI  - Differential neural activation of vascular alpha-adrenoceptors in oral tissues of
      cats.
AB  - The aim of this study was to determine the relative contribution of alpha(1)- and
      alpha(2)-adrenoceptors involved in sympathetic-evoked vasoconstrictor responses
      in tissues perfused by the lingual arterial circulation in pentobarbital
      anesthetized cats. Blood flow in the lingual artery was measured by ultrasonic
      flowmetry. Laser-Doppler flowmetry was utilized to measure oral tissue
      vasoconstrictor responses in the maxillary gingiva and from the surface of the
      tongue. Electrical stimulation of the preganglionic superior cervical sympathetic
      nerve resulted in frequency-dependent blood flow decreases at all three sites.
      These responses were stable over time and were uniformly antagonized by
      administration of phentolamine (0.3 - 3.0 mg kg(-1)). The selective alpha(1)
      adrenoceptor antagonist, prazosin (10 - 300 microg kg(-1)), attenuated
      vasoconstriction in the lingual artery and gingiva, but was ineffective in
      blocking vasoconstriction in the tongue. Subsequent administration of rauwolscine
      (300 microg kg(-1)) antagonized remaining vasoconstrictor responses. In contrast,
      rauwolscine (10 - 300 microg kg(-1)), given alone, blocked evoked
      vasoconstriction in the tongue, and was without effect on gingival or lingual
      artery vasoconstrictor responses. Subsequent administration of prazosin (300
      microg kg(-1)) largely antagonized remaining neurally elicited responses. These
      results suggest that neural vasoconstrictor responses in some regional vascular
      beds in the cat oral cavity are mediated by both alpha(1)- and alpha(2)
      adrenoceptors. In contrast, tongue surface vasoconstrictor responses to
      sympathetic nerve activation appear to be mediated primarily by alpha(2)
      adrenoceptors.

PMID- 11959090
TI  - Effects of cyclooxygenase-1/cyclooxygenase-2 inhibition on leukocyte/endothelial
      cell interactions in the rat mesentery.
AB  - Nonsteroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase activity and
      cause gastrointestinal damage in part by promoting leukocyte accumulation in the
      mucosa. Our aim was to evaluate the effects of selective blockade of the
      isoenzymes cyclooxygenase-1 and cyclooxygenase-2 on leukocyte adhesion in vivo.
      Leukocyte/endothelial cell interactions were examined in rat mesenteric venules
      before and after treatment with indomethacin, SC-560 (5-(4-chlorophenyl)-1-(4
      methoxyphenyl)-3-trifluoromethylpyrazole, cyclooxygenase-1 inhibitor), DFP (5,5
      dimethyl-3-(2-propoxy)-4-(4-methanesulfonyl)-2(5H)-furanone, cyclooxygenase-2
      inhibitor), or SC-560 plus DFP (20 mg/kg, i.v. each). Indomethacin increased
      leukocyte-rolling flux, reduced rolling velocity and elicited significant
      leukocyte adhesion. Neither SC-560 nor DFP induced these effects although their
      co-administration reproduced the indomethacin response. Indomethacin and SC-560,
      but not DFP, abolished cyclooxygenase-1 activity in blood. Plasma from
      indomethacin- or DFP-, but not from SC-560-treated rats abolished cyclooxygenase
      2 activity in activated A549 cells. Specific blockade of cyclooxygenase-1 or
      cyclooxygenase-2 does not induce any inflammatory event in the rat mesentery and
      the inflammatory response observed with non-selective NSAIDs seems to be due to
      the inhibition of both isoenzymes.

PMID- 11959089
TI  - Effect of a BLT receptor antagonist in a model of severe ischemia and reperfusion
      injury in the rat.
AB  - Pharmacological strategies which limit neutrophil recruitment may also limit the
      damage induced by the reperfusion of an ischemic vascular territory. In the
      present study, we have investigated the effects of the BLT receptor antagonist,
      CP-105,696 ((+)-1-(3S,4R)-[3-(4-phenyl-benzyl)-4-hydroxy-chroman-7-yl]
      cyclopentane carboxylic acid), on the local, remote and systemic inflammatory
      changes observed during severe intestinal ischemia (120 min) and reperfusion (120
      min) injury. The post-ischemic treatment with CP-105,696 (3 mg/kg) virtually
      abolished the increase in vascular permeability, but not neutrophil accumulation,
      in the intestine and lungs. CP-105,696 partially inhibited the reperfusion
      induced neutropenia, but failed to affect intestinal haemorrhage or lethality. CP
      105,696 had no inhibitory effect on the local and systemic increases in the
      concentrations of tumour necrosis factor (TNF-alpha), interleukin-1 beta and
      interleukin-10, but markedly suppressed interleukin-6. Overall, our results show
      that activation of BLT receptor plays a minor role in the local, remote and
      systemic injuries following severe ischemia and reperfusion in rats.

PMID- 11959091
TI  - The role of histamine H(1) receptors in late-phase reaction of allergic
      conjunctivitis.
AB  - The role of histamine H(1) receptors in the late-phase reaction of allergic
      conjunctivitis was studied using histamine H(1) receptor-deficient mice. To
      clarify the eosinophil infiltration, which is a reliable indicator of late-phase
      reaction, eosinophil peroxidase activity in the conjunctiva was measured. Mice
      were actively immunized with ovalbumin, and conjunctivitis was induced by topical
      instillation of ovalbumin. A significantly high eosinophil peroxidase level in
      the conjunctiva was observed in sensitized wild-type mice, whereas sensitized
      histamine H(1) receptor-deficient mice showed no significant increase in the
      conjunctival eosinophil peroxidase level. In addition, the elevation of
      eosinophil peroxidase level observed in sensitized wild-type mice was
      significantly antagonized by pretreatment with anti-P-selectin antibody. From
      these findings, it was concluded that eosinophil infiltration into the
      conjunctival tissue in late-phase reaction of allergic conjunctivitis is mediated
      by P-selectin stored in endothelial cells via histamine H(1) receptors.

PMID- 11959092
TI  - MAP kinase mediates growth factor-induced nuclear translocation of estrogen
      receptor alpha.
AB  - In addition to mediating the classical transcriptional effects of estrogen,
      estrogen receptors (ERs) are now known to regulate gene expression in the absence
      of estrogen by ligand-independent activation pathways, and to mediate the rapid,
      non-genomic effects of estrogen as well. ERs have been shown to associate with
      the cell membrane, and recent studies demonstrate that this subpopulation of
      membrane-associated ER mediates the rapid effects of estrogen. To date, however,
      little is known regarding the pathways that regulate the distribution of the ER
      between the nuclear and membrane fractions. In the current study, we demonstrate
      membrane localization of transiently transfected ERalpha in human vascular smooth
      muscle cells, and translocation of ERalpha from the membrane to the nucleus in
      response to both estrogen-dependent and estrogen-independent stimulation.
      Mutational analyses identified serine 118 as the critical residue regulating
      nuclear localization following estrogen-independent stimulation, but not
      following estrogen stimulation. Induction of nuclear localization of ERalpha by
      estrogen-independent, but not estrogen-dependent stimulation was blocked by both
      pharmacologic and genetic inhibition of mitogen-activated protein (MAP) kinase
      activation. Furthermore, constitutive activation of MAP kinase resulted in
      nuclear translocation of ERalpha. These overexpression studies support that MAP
      kinase-mediated phosphorylation of ERalpha induces nuclear localization of the ER
      in response to estrogen-independent, but not estrogen-dependent stimulation,
      demonstrating stimulus-specific molecular pathways regulate the nuclear
      localization of the ER. These findings identify a previously unrecognized pathway
      that regulates the intracellular localization of the ER, and represent the first
      demonstration that the distribution of the ER between membrane and nuclear
      compartments is regulated by physiologic stimuli.

PMID- 11959093
TI  - Mutations in the S4-H2 loop of eIF4E which increase the affinity for m7GTP.
AB  - Eukaryotic initiation factor 4E (eIF4E) binds the 5'-cap of eukaryotic mRNAs and
      overexpression of eIF4E in epithelial cell cancers correlates with the
      metastases/tissue invasion phenotype. Photolabeling of eIF4E with [gamma-32P]8
      azidoguanosine 5'-triphosphate (8-N3GTP) demonstrated cross-linking at Lys-119 in
      the S4-H2 loop which is distant from the m7GTP binding site [Marcotrigiano et al.
      (1997) Cell 89, 951-961; Friedland et al. (1997) Protein Sci. 6, 125-131].
      Modeling studies indicate that 8-N3GTP cross-linked with Lys-119 because it binds
      a site that is occupied by the second nucleotide of a bound mRNA. Mutagenesis of
      the S4-H2 loop produced proteins with a 5-10-fold higher affinity for m7GTP than
      wild-type eIF4E. These mutants of eIF4E may have uses in selectively purifying
      mRNAs with intact 5'-ends or in determining how the promyelocytic leukemia
      protein decreases the affinity of eIF4E for mRNA caps.

PMID- 11959094
TI  - Reactive oxygen species inhibit the succinate oxidation-supported generation of
      membrane potential in wheat mitochondria.
AB  - In order to gain a first insight into the effects of reactive oxygen species
      (ROS) on plant mitochondria, we studied the effect of the ROS producing system
      consisting of xanthine plus xanthine oxidase on the rate of membrane potential
      (DeltaPsi) generation due to either succinate or NADH addition to durum wheat
      mitochondria as monitored by safranin fluorescence. We show that the early ROS
      production inhibits the succinate-dependent, but not the NADH-dependent, DeltaPsi
      generation and oxygen uptake. This inhibition appears to depend on the impairment
      of mitochondrial permeability to succinate. It does not involve mitochondrial
      thiol groups sensitive to either mersalyl or N-ethylmaleimide and might involve
      both protein residues and/or membrane lipids, as suggested by the mixed nature.
      We propose that, during oxidative stress, early generation of ROS can affect
      plant mitochondria by impairing metabolite transport, thus preventing further
      substrate oxidation, DeltaPsi generation and consequent large-scale ROS
      production.

PMID- 11959095
TI  - Selected BTB/POZ-kelch proteins bind ATP.
AB  - Proteins with a bric-a-brac, tramtrack, broad-complex/Poxvirus zinc fingers
      (BTB/POZ) domain are implicated in a broad variety of biological processes,
      including DNA binding, regulation of gene transcription and organization of
      macromolecular structures. Kelch domain containing BTB/POZ proteins like Mayven
      and Keap1 display limited sequence similarity with the actin-fragmin kinase from
      Physarum, a protein kinase with a kelch domain. We show that mouse Keap1, a
      Caenorhabditis elegans protein that we named CKR, and human Mayven bind 5'-p
      fluorosulfonyl-benzoyl-adenosine (FSBA), a covalently modifying ATP analogue.
      Binding with 2-azido-ATP or ATP-Sepharose is also demonstrated. In contrast to
      Mayven, FSBA binding by CKR and Keap1 was specifically inhibited by excess ATP.
      The ATP binding pocket is located in the N-terminal half of Keap1. Our findings
      indicate that several, but not all, BTB/POZ-kelch domain proteins possess an
      inconspicuous ATP binding cassette.

PMID- 11959097
TI  - Substrate interferes with dimerisation of outer membrane phospholipase A.
AB  - Outer membrane phospholipase A (OMPLA) activity is regulated by reversible
      dimerisation with the dimer being the active species. Observed lag phases in
      activity indicated that dimerisation may be slow relative to turnover. A covalent
      OMPLA dimer indeed did not display lag phase behaviour. A model for OMPLA
      kinetics was proposed accounting for a slow dimerisation step. Preincubation
      conditions determined the initial amount of monomer and influenced both lag times
      and final activities. Under the conditions used, substrate concentrations higher
      than 50 mol% inhibited OMPLA activity and increased lag times. Our results may
      shed more light on mechanisms controlling OMPLA activity in vivo.

PMID- 11959096
TI  - The Sambucus nigra type-2 ribosome-inactivating protein SNA-I' exhibits in planta
      antiviral activity in transgenic tobacco.
AB  - Transgenic tobacco (Samsun NN) plants transformed with a cDNA clone encoding SNA
      I' from Sambucus nigra synthesize, and correctly process and assemble, a fully
      active type-2 ribosome-inactivating protein. Expression of SNA-I' under the
      control of the 35S cauliflower mosaic virus promoter enhances the plant's
      resistance against infection with tobacco mosaic virus. In contrast to type-1
      ribosome-inactivating proteins, the expression of SNA-I' does not affect the
      growth and fertility of the transgenic plants and is not accompanied by an
      increased expression of pathogenesis-related proteins indicating that its
      antiviral activity most probably differs from that of pokeweed antiviral protein.

PMID- 11959098
TI  - Excess noise in modified conductance states following the interaction of ryanoids
      with cardiac ryanodine receptor channels.
AB  - The interaction of ryanodine with the ryanodine receptor (RyR) produces profound
      changes in channel function. Open probability increases dramatically and
      conductance is reduced. In this report we describe differences in the properties
      of reduced conductance states produced by the interaction of ryanodine
      derivatives with RyR channels. Some reduced conductance states are considerably
      noisier than the normal open state of the RyR channel. Inspection and analysis of
      these events reveals that the excess noise arises from transitions between two
      conductance states. Following the interaction of certain ryanodine derivatives,
      RyR channels undergo transitions between two conformations with slightly
      different ion-handling properties.

PMID- 11959099
TI  - The reaction order of the dissociation reaction of the B820 subunit of
      Rhodospirillum rubrum light-harvesting I complex.
AB  - We have studied the equilibrium between the dissociated B777 form (absorbing at
      777 nm) of the light-harvesting complex of Rhodospirillum rubrum and the
      oligomeric B820 form. Analysis of the reaction order for the B820 dissociation
      reaction to form B777 shows that this reaction depends on the concentration of
      octylglucoside detergent (n-octyl-beta-D-glucopyranoside (betaOG)) present in the
      sample. At low betaOG concentrations (less than 1.2%) this reaction requires two
      components, presumably one alpha-B777 and one beta-B777, implying that the B820
      subunit is a dimer. At higher betaOG concentrations this reaction requires four
      components, implying that B820 is a tetramer. These results partly explain the
      discrepancies in the literature about the stoichiometry of B820 and open an
      original way for studying protein-detergent interactions.

PMID- 11959100
TI  - Docking studies reveal a selective binding of D-penicillamine to the
      transactivator protein of human immunodeficiency virus type 1.
AB  - DOCK and Affinity studies were carried out to study the binding of D- and L
      penicillamine to the transactivator protein (tat) of human immunodeficiency virus
      type 1 (HIV-1). These studies reveal a selective binding of D-penicillamine to
      the cysteine-rich region covering amino acid residues 20-38 of the tat protein. A
      careful analysis of the components of the binding energy of the D- and L-isomers
      reveals that the D-isomer has a more favorable van der Waals interaction
      resulting from an optimal placement of the dimethylthiomethyl side chain in the
      binding site. This observation matches the experimental data that D-penicillamine
      is a more potent inhibitor of tat-mediated transactivation than the L-isomer. The
      docking and experimental data offer an interesting approach to design structural
      molecules with potential application to block signal functions of the tat protein
      in HIV-1 pathogenesis.

PMID- 11959101
TI  - Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors in
      malignant melanoma and HaCaT keratinocytes.
AB  - We examined the biological effects of the ceramide analogues (1S,2R)-2-N
      myristoylamino-1-phenyl-1-propanol (D-e-MAPP) and (1R,2R)-2-N-myristoylamino-1-(4
      nitrophenyl)-1,3-propandiol (D-NMAPPD) on human HaCaT keratinocytes and human
      melanoma cells. We could demonstrate that D-e-MAPP and D-NMAPPD are able to
      suppress acid ceramidase activity. The elevation of the endogenous level of
      ceramide is followed by induction of apoptosis and suppression of proliferation
      in HaCaT keratinocytes. Moreover, we recently identified a group of human
      melanoma cell populations which are heterogeneously susceptible to C2-ceramide
      mediated apoptosis. Studies with these melanoma cells revealed correlation
      between ceramide-mediated apoptosis and D-NMAPPD-induced apoptosis, confirming
      the effect of this inhibitor on ceramide signaling in human melanoma cells. These
      findings suggest ceramidase inhibitors as a potential new therapeutical class of
      antiproliferative and cytostatic drugs.

PMID- 11959102
TI  - Extended longevity of Caenorhabditis elegans by knocking in extra copies of
      hsp70F, a homolog of mot-2 (mortalin)/mthsp70/Grp75.
AB  - The Caenorhabditis elegans homolog of mortalin/mthsp70/Grp75 (called mot-2
      hereafter) was isolated by screening of a nematode cDNA library with mouse mot-2
      cDNA. The isolated clone matched to hsp70F of C. elegans. Analysis with two of
      the antibodies raised against hsp70F revealed that unlike mammalian mot-2, it is
      heat inducible. Transient induction of hsp70F by heat shock led to a slight
      (<13%) extension in the C. elegans life span. The transgenic worms that
      constitutively over-expressed hsp70F predominantly in muscle showed life span
      extension (approximately 43% for mean and approximately 45% for maximum life
      span) as compared to the wild-type and green fluorescent protein-transgenic
      worms. Life span extension of human cells was obtained by over-expression of mot
      2 [Kaul et al. (2000) FEBS Lett. 474, 159-164]. Our results show, for the first
      time, that this member of the hsp70 family governs the longevity of worms and
      thus there are common pathways that determine mammalian and worm longevity.

PMID- 11959103
TI  - Lamellipodial localization of Dictyostelium myosin heavy chain kinase A is
      mediated via F-actin binding by the coiled-coil domain.
AB  - Myosin heavy chain kinase A (MHCK A) modulates myosin II filament assembly in the
      amoeba Dictyostelium discoideum. MHCK A localization in vivo is dynamically
      regulated during chemotaxis, phagocytosis, and other polarized cell motility
      events, with preferential recruitment into anterior filamentous actin (F-actin)
      rich structures. The current work reveals that an amino-terminal segment of MHCK
      A, previously identified as forming a coiled-coil, mediates anterior
      localization. MHCK A co-sediments with F-actin, and deletion of the amino
      terminal domain eliminated actin binding. These results indicate that the
      anterior localization of MHCK A is mediated via direct binding to F-actin, and
      reveal the presence of an actin-binding function not previously detected by
      primary sequence evaluation of the coiled-coil domain.

PMID- 11959105
TI  - Nicotine-modulated formation of spiroiminodihydantoin nucleoside via 8-oxo-7,8
      dihydro-2'-deoxyguanosine in 2'-deoxyguanosine-hypochlorous acid reaction.
AB  - Hypochlorous acid (HOCl) is generated by myeloperoxidase of activated neutrophils
      which kill invading microorganisms, but also cause DNA damage in inflamed
      tissues. We report here that spiroiminodihydantoin nucleoside (dS), a further
      oxidized product of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), is formed, in
      addition to 8-chloro-2'-deoxyguanosine and 8-oxo-dG, by reaction of 2'
      deoxyguanosine with HOCl. Presence of low concentrations of nicotine
      significantly enhanced the yields of these HOCl-modified nucleosides. Our results
      imply that nicotine may enhance genotoxicity and tissue damage caused by
      neutrophil activation. dS may also serve as a new biomarker for oxidative DNA
      damage induced by oxidants such as HOCl.

PMID- 11959104
TI  - Involvement of tumor necrosis factor alpha, rather than interleukin-1alpha/beta
      or nitric oxides in the heme oxygenase-1 gene expression by lipopolysaccharide in
      the mouse liver.
AB  - Heme oxygenase-1 (HO-1) is induced under various oxidative stress conditions,
      such as lipopolysaccharide (LPS) insult. Induction of HO-1 by LPS is reported to
      be mediated through interleukin-1beta (IL-1beta), rather than other inflammatory
      cytokines in the mouse liver. However, we found that IL-1alpha/beta knockout (KO)
      mice responded well to LPS insult, as did wild-type mice with respect to HO-1
      mRNA induction (about 30-fold increase). In contrast, tumor necrosis factor alpha
      KO (TNFalphaKO) mice responded very weakly to LPS in the HO-1 mRNA expression,
      but not metallothionein mRNA. Recent studies reveal that nitric oxide from
      Kupffer cells is involved in HO-1 induction in the liver produced by LPS.
      Therefore, nitrite and nitrate concentrations in the liver were also measured and
      these parameters did not increase in either IL-1KO or TNFalphaKO. In addition,
      the phosphorylation of c-JUN N-terminal kinase (JNK) and p38, but not
      extracellular signal-regulated kinase, was very low in TNFalphaKO mice due to LPS
      administration. All of these findings indicate that TNFalpha is a major candidate
      to trigger HO-1 induction in response to LPS stimulation, and that its message is
      likely transduced through JNK and p38 pathways.

PMID- 11959106
TI  - Human fibroblasts in vitro senesce with a donor-specific telomere length.
AB  - In human fibroblasts, replicative senescence, telomere length and donor age are
      closely interrelated. We analyzed these relationships for fibroblast strains from
      14 healthy human donors in the age range of 28-90 years. In vitro replicative
      capacity was correlated more closely with donor age than with telomere length ex
      vivo, especially for healthy donors. Telomere length at senescence was as
      variable as at cell explantation and increased with donor age. The data suggest a
      donor-specific, age-dependent regulation of the telomere length threshold that
      triggers senescence in human fibroblasts.

PMID- 11959107
TI  - Kinetics of precursor cleavage at the dibasic sites. Involvement of peptide
      dynamics.
AB  - The presence in the P'1 position relative to the LysArg doublet of either Phe,
      Tyr or Trp residues affects only pro-OT/Np(7-15) flexibility. This has a
      measurable effect on the dynamics of the peptide. Since the same modifications
      have a major influence on the K(m) and V(max) values of the peptide cleavage,
      these kinetic parameters should depend on the peptide substrate motions.
      Therefore, the primary kinetic contribution of substrate cleavage should arise
      from substrate dynamics rather than from the enzyme.

PMID- 11959108
TI  - A naturally occurring NAR variable domain binds the Kgp protease from
      Porphyromonas gingivalis.
AB  - The new antigen receptor (NAR) from sharks consists of a single immunoglobulin
      variable domain attached to five constant domains, and is hypothesised to
      function as an antibody. Two closely related NARs with affinity for the Kgp
      (lysine-specific) gingipain protease from Porphyromonas gingivalis were selected
      by panning an NAR variable domain library. When produced in Escherichia coli,
      these recombinant NARs were stable, correctly folded, and specifically bound Kgp
      (K(d)=1.31+/-0.26x10(-7) M). Binding localised to the Kgp adhesin domains,
      however without inhibiting adhesin activity. These naturally occurring proteins
      indicate an immune response to pathogenic bacteria and suggest that the NAR is a
      true antibody-like molecule.

PMID- 11959109
TI  - Differentiation of single-cell organisms according to elongation stages crucial
      for gene expression efficacy.
AB  - We analyzed the interrelation between the efficiency of a gene expression and the
      nucleotide composition of all protein-coding sequences in 38 unicellular
      organisms whose complete genomic sequences are known. These organisms comprise 37
      prokaryotic (29 eubacteria and eight archaebacteria) and one eukaryotic (yeast)
      species. We demonstrated that frequency analysis of gene codon composition fails
      to reflect adequately the gene expression efficiency of all these organisms. We
      constructed a measure, the elongation efficiency index, that considers
      simultaneously the information on codon frequencies and the degree of mRNA local
      self-complementarity. This measure recognizes the ribosome-coding genes as highly
      expressed in all the unicellular organisms studied. According to our analysis,
      these species fall into five groups differentiated by the process that makes the
      key contribution to the elongation rate.

PMID- 11959110
TI  - NMR measurement of the off rate from the first calcium-binding site of the
      synaptotagmin I C2A domain.
AB  - The off rate from the first calcium-binding site of the C2A domain of
      synaptotagmin I, a putative calcium receptor in neurotransmitter release, has
      been determined by 15N-nuclear magnetic resonance relaxation dispersion
      measurements. The exchange rate was obtained by fitting the dependence of the
      transverse relaxation rates on the interval between 180 degrees pulses in
      relaxation-compensated CPMG experiments at 3.2 microM calcium concentration. The
      measured k(ex) is 2.0x10(3) x s(-1). The calcium on rate of 3.5+/-1x10(7) x s(
      1), determined from the measured off rate and the dissociation constant (5.3x10(
      5) M), is close to the diffusion limit. These results are consistent with the
      proposed role of synaptotagmin I as a calcium sensor in release, but suggest that
      additional factors may help to accelerate the diffusion of Ca2+ to the sensor.

PMID- 11959111
TI  - Presence of a novel subset of NKT cells bearing an invariant V(alpha)19.1
      J(alpha)26 TCR alpha chain.
AB  - CD1d-deficient (CD1d-/-) mouse lymphocytes were analyzed to classify the natural
      killer T (NKT) cells without reactivity to CD1d. The cells bearing a V(alpha)19.1
      J(alpha)26 (AV19-AJ33) invariant TCR alpha chain, originally found in the
      peripheral blood lymphocytes, were demonstrated to be abundant in the NK1.1+ but
      not NK1.1- T cell population isolated from CD1d-/- mice. Moreover, more than half
      (11/21) of the hybrid cell lines established from CD1d-/- NKT cells expressed the
      V(alpha)19.1-J(alpha)26 invariant TCR alpha chain. The expression of the
      invariant V(alpha)19.1-J(alpha)26 mRNA was absent in beta2-microglobulin
      deficient mice. Collectively, the present findings suggest the presence of a
      second NKT cell repertoire characterized by an invariant TCR alpha chain
      (V(alpha)19.1-J(alpha)26) that is selected by an MHC class I-like molecule other
      than CD1d.

PMID- 11959112
TI  - Intracellular calcium mobilization induces period genes via MAP kinase pathways
      in NIH3T3 cells.
AB  - Mammalian period genes have a pivotal role in generating circadian rhythms and
      are rapidly induced by several stimuli in mammalian cells. In the present study,
      we revealed that treatment with thapsigargin significantly induced transcripts of
      mouse period 1 and 2 (mPer1 and mPer2) but not mPer3 among circadian related
      genes in NIH3T3 cells. Thapsigargin-induced mPer1 and mPer2 mRNA expressions took
      distinct signaling pathways from protein kinase C and cAMP, but were partially
      inhibited by inhibitors of MEK1 and p38 mitogen-activated protein kinase,
      respectively. Thus, the present study suggested that intracellular calcium is one
      of multiple signaling stimuli triggering mPer gene expression in NIH3T3 cells.

PMID- 11959113
TI  - Cleavage of a tail-anchored protein by signal peptidase.
AB  - Tail-anchored proteins are post-translationally targeted and inserted into the
      endoplasmic reticulum membrane. They do not use the co-translational signal
      recognition particle (SRP)-dependent pathway, but rather utilize an ill-defined,
      ATP-dependent mechanism. Here, we show that a tail-anchored protein can be
      cleaved by signal peptidase and that the sequence requirements for efficient
      cleavage seem to be the same as for cleavage of co-translationally targeted SRP
      dependent proteins.

PMID- 11959114
TI  - The Fluorosome technique for investigating membrane on- and off-loading of drugs
      by beta-CD and sonicated SUV.
AB  - The application of the Fluorosome technique to test drug delivery systems is
      described. Fluorosomes, egg phosphatidylcholine liposomes with bilayer embedded
      fluorophores, were employed to investigate the ability of sonicated small
      unilamellar vesicles (sSUV) and beta-cyclodextrins (beta-CD) to deliver drugs
      into or extract drugs from the fluorosome's phospholipid bilayer. The addition of
      phloretin to a fluorosome suspension resulted in fluorescence reduction
      reflecting phloretin entering the bilayer and quenching fluorophore fluorescence.
      Subsequent addition of sSUV to phloretin pretreated fluorosomes showed an
      increase in fluorescence reflecting phloretin extraction from the fluorosome
      membrane. Sequential additions of beta-estradiol loaded beta-CD to fluorosomes as
      well as the addition of beta-estradiol alone resulted in fluorescence reduction
      due to beta-estradiol insertion into the membrane. Further addition of pure beta
      CD resulted in a fluorescence increase indicating beta-estradiol extraction from
      the fluorosome membrane.

PMID- 11959115
TI  - Mining functional relationships in feature subspaces from gene expression
      profiles and drug activity profiles.
AB  - In an effort to determine putative functional relationships between gene
      expression patterns and drug activity patterns of 60 human cancer cell lines, a
      novel method was developed to discover local associations within cell line
      subsets. The association of drug-gene pairs is an explorative way of discovering
      gene markers that predict clinical tumor sensitivity to therapy. Nine drug-gene
      networks were discovered, as well as dozens of gene-gene and drug-drug networks.
      Three drug-gene networks with well studied members were discussed and the
      literature shows that hypothetical functional relationships exist. Therefore,
      this method enables the gathering of new information beyond global associations.

PMID- 11959116
TI  - Regulation of the heme A biosynthetic pathway in Saccharomyces cerevisiae.
AB  - Biosynthesis of heme A, a prosthetic group of cytochrome oxidase (COX), involves
      an initial farnesylation of heme B. The heme O product formed in this reaction is
      modified by hydroxylation of the methyl group at carbon C-8 of the porphyrin
      ring. This reaction was proposed to be catalyzed by Cox15p, ferredoxin, and
      ferredoxin reductase. Oxidation of the alcohol to the corresponding aldehyde
      yields heme A. In the present study we have assayed heme A and heme O in yeast
      COX mutants. The steady state concentrations of the two hemes in the different
      strains studied indicate that hydroxylation of heme O, catalyzed by Cox15p, is
      regulated either by a subunit or assembly intermediate of COX. The heme profiles
      of the mutants also suggest positive regulation of heme B farnesylation by the
      hydroxylated intermediate formed at the subsequent step or by Cox15p itself.

PMID- 11959117
TI  - Beta-arrestin is involved in the desensitization but not in the internalization
      of the somatostatin receptor 2A expressed in CHO cells.
AB  - The interaction of beta-arrestin-1 with the somatostatin receptor type 2A (sst2A)
      was monitored using both biochemical and confocal imaging approaches. We show
      that, using transient transfection of either beta-arrestin-1 or its dominant
      negative Delta-arrestin-1 in CHO cells stably transfected with the sst2A, beta
      arrestin-1 is colocalized with the receptor in endosomal vesicles after
      somatostatin-induced sequestration. However, this interaction leads to a role of
      beta-arrestin-1 in the desensitization of the sst2A rather than in the
      internalization process of the receptor-ligand complex.

PMID- 11959118
TI  - Conformational analysis of the GTP-binding protein MxA using limited proteolysis.
AB  - Guanosine triphosphate (GTP)-binding proteins are known to function as molecular
      switches that cycle between GTP-bound and guanosine diphosphate (GDP)-bound
      states. Switching is achieved by the fact that G-proteins in the GTP-bound
      conformation can interact with a certain set of effector molecules while they
      interact with a different set of partners in their GDP-bound conformation. The
      antiviral properties of the interferon-induced MxA protein are critically
      dependent on the ability of MxA to bind GTP. Using limited proteolysis we
      analyzed the conformations of the MxA protein under nucleotide-free, GDP-bound,
      and GTP-bound conditions. We find that whereas the conformations of nucleotide
      free MxA and GDP-bound MxA are essentially similar, GTP-binding causes a dramatic
      change in the conformation of MxA.

PMID- 11959119
TI  - Identification of ten exon deleted ERbeta mRNAs in human ovary, breast, uterus
      and bone tissues: alternate splicing pattern of estrogen receptor beta mRNA is
      distinct from that of estrogen receptor alpha.
AB  - Four different human tissues and breast cancer cell lines were screened to
      identify exon deletion variant transcripts of estrogen receptor beta (ERbeta) by
      reverse transcription-polymerase chain reaction using the 'splice targeted primer
      approach' that amplifies each category of exon deleted variants as a separate
      gene population. A total of 10 different variant mRNAs that have deletions in
      various combination of exons were identified by sequence analysis. They were exon
      2Delta; exons 2 and 5-6Delta; exon 3Delta; exon 4Delta; exon 5Delta; exons 5 and
      2Delta; exon 6Delta; exons 6 and 2Delta; exons 6, 2-3Delta; and exons 5-6Delta.
      In some cases, deletion of an exon appears to be associated with a mutation of a
      specific base. Although ERalpha and ERbeta are highly homologous, have identical
      exon and functional domain organization, exhibit similar ligand-binding profiles
      and interact with identical DNA response elements, the sequence of exon skipping
      in ERbeta pre-mRNA appears to be distinct from that of ERalpha mRNA. Furthermore,
      results described here also suggest that alternate splicing of ERbeta mRNA is
      tissue specific. The presence of a ERbeta variant profile together with other ER
      isoforms in a tissue may have functional implications in binding and response to
      a particular ligand.

PMID- 11959121
TI  - Sequence and electron paramagnetic resonance analyses of nitrate reductase NarGH
      from a denitrifying halophilic euryarchaeote Haloarcula marismortui.
AB  - Genes encoding the NarG and NarH subunits of the molybdo-iron-sulfur enzyme, a
      nitrate reductase from a denitrifying halophilic euryarchaeota Haloarcula
      marismortui, were cloned and sequenced. An incomplete cysteine motif reminiscent
      of that for a [4Fe-4S] cluster binding was found in the NarG subunit, and
      complete cysteine arrangements for binding one [3Fe-4S] cluster and three [4Fe
      4S] clusters were found in the NarH subunit. In conjunction with chemical,
      electron paramagnetic resonance, and subcellular localization analyses, we firmly
      establish that the H. marismortui enzyme is a new archaeal member of the known
      membrane-bound nitrate reductases whose homologs are found in the bacterial
      domain.

PMID- 11959120
TI  - Differential stability of tetraspanin/tetraspanin interactions: role of
      palmitoylation.
AB  - The tetraspanins associate with various surface molecules and with each other to
      build a network of molecular interactions, the tetraspanin web. The interaction
      of tetraspanins with each other seems to be central for the assembly of the
      tetraspanin web. All tetraspanins studied, CD9, CD37, CD53, CD63, CD81, CD82 and
      CD151, were found to incorporate [3H]palmitate. By site-directed mutagenesis, CD9
      was found to be palmitoylated at any of the four internal juxtamembrane regions.
      The palmitoylation of CD9 did not influence the partition in detergent-resistant
      membranes but contributed to the interaction with CD81 and CD53. In particular,
      the resistance of the CD9/CD81 interaction to EDTA, which disrupts other
      tetraspanin/tetraspanin interactions, was entirely dependent on palmitoylation.

PMID- 11959123
TI  - A specific role for tocopherol and of chemical singlet oxygen quenchers in the
      maintenance of photosystem II structure and function in Chlamydomonas
      reinhardtii.
AB  - alpha-Tocopherol concentrations were determined at low and high light intensities
      and compared with the rate of photosynthesis, photosystem II (PS II) and its
      reaction center D1 protein. Blocking of tocopherol biosynthesis at the 4
      hydroxyphenylpyruvate dioxygenase by the herbicide pyrazolynate led to a quick
      disappearance of alpha-tocopherol in high light, as well as of PS II activity and
      the D1 protein. Homogentisic acid rescued all activities. It is concluded that
      alpha-tocopherol has a continuous turnover as a scavenger of the singlet oxygen
      that arises from the quenching by oxygen of the triplet of the PS II reaction
      center and triggers the degradation of the D1 protein. Thus tocopherols are
      essential to keep photosynthesis active. We suggest that this is why plants make
      and need tocopherols. Chemical quenchers of singlet oxygen, notably
      diphenylamines, completely protect PS II, prevent D1 protein degradation and keep
      tocopherol levels even at very high light intensities. This supports the notion
      that 1O2 is the intermediate in light triggered D1 protein turnover.

PMID- 11959122
TI  - Modelling Alzheimer-specific abnormal Tau phosphorylation independently of
      GSK3beta and PKA kinase activities.
AB  - In Alzheimer's disease, neurofibrillary degeneration results from the aggregation
      of abnormally phosphorylated Tau proteins into paired helical filaments. These
      Tau variants displayed specific epitopes that are immunoreactive with anti
      phospho-Tau antibodies such as AT100. As shown in in vitro experiments, glycogen
      synthase kinase 3 beta (GSK3beta) and protein kinase A (PKA) may be key kinases
      in these phosphorylation events. In the present study, Tau was microinjected into
      Xenopus oocytes. Surprisingly, in this system, AT100 was generated without any
      GSK3beta and PKA contribution during the progesterone or insulin-induced
      maturation process. Our results demonstrate that a non-modified physiological
      process in a cell model can generate the most specific Alzheimer epitope of Tau
      pathology.

PMID- 11959124
TI  - The YbgC protein encoded by the ybgC gene of the tol-pal gene cluster of
      Haemophilus influenzae catalyzes acyl-coenzyme A thioester hydrolysis.
AB  - This paper examines the catalytic function of the protein YbgC, encoded by the
      ybgC gene of the tol-pal gene cluster in Haemophilus influenzae. The YbgC
      protein, a homologue of the Pseudomonas sp. strain CBS3 4-hydroxybenzoyl-coenzyme
      A thioesterase, conserves the active site Asp residue associated with
      thioesterase activity. The H. influenzae ybgC gene was cloned and overexpressed
      in Escherichia coli. The recombinant protein was purified and tested for
      thioesterase activity towards acyl-CoA and acyl-N-acetylcysteamine thioesters.
      The YbgC protein catalyzes the hydrolysis of short chain aliphatic acyl-CoA
      thioesters, while the D18N YbgC mutant protein (prepared to serve as a control)
      does not.

PMID- 11959125
TI  - The plant Rad50-Mre11 protein complex.
AB  - The Rad50-Mre11-Xrs2/Nbs1 protein complex plays critical roles in cellular
      processes involving DNA ends. This complex is implicated in DNA recombination and
      replication, meiosis, telomere maintenance and cellular DNA damage responses. The
      Rad50 and Mre11 proteins are essential for viability in animals, although not in
      yeast. We have prepared antibodies to the Rad50 protein of the model plant
      Arabidopsis thaliana which recognize a 175 kDa protein in wild-type Arabidopsis
      protein extracts. Furthermore, we report here demonstration of the existence of
      the Rad50-Mre11 complex by co-immunoprecipitation of the Rad50 and Mre11 proteins
      from the plant cell extracts.

PMID- 11959126
TI  - Action spectrum of psbA gene transcription is similar to that of photoinhibition
      in Synechocystis sp. PCC 6803.
AB  - The photosystem II (PSII) reaction center protein D1 undergoes rapid light
      dependent turnover, which is caused by photoinhibition. To identify the
      photoreceptor(s) involved in the light-dependent expression of the psbA gene
      encoding the D1 protein, we determined the action spectra of psbA transcription,
      PSII activity, photosynthesis and photoinhibition in Synechocystis sp. PCC 6803.
      In accordance with its phycobilisome antenna, PSII showed the highest activity in
      the spectral region from yellow to red and only low activity in the ultraviolet-A
      (UV-A) to green region. Photoinhibition, in turn, was fastest in UV-A to violet
      light and a minor peak was found in the orange region. The action spectrum of
      psbA transcription resembled closely that of photoinhibition, suggesting that
      photoinhibition creates a signal for up-regulation of the psbA gene.

PMID- 11959127
TI  - The roles of hydrogenases 3 and 4, and the F0F1-ATPase, in H2 production by
      Escherichia coli at alkaline and acidic pH.
AB  - The hyc operon of Escherichia coli encodes the H2-evolving hydrogenase 3 (Hyd-3)
      complex that, in conjunction with formate dehydrogenase H (Fdh-H), constitutes a
      membrane-associated formate hydrogenlyase (FHL) catalyzing the disproportionation
      of formate to CO2 and H2 during fermentative growth at low pH. Recently, an
      operon (hyf) encoding a potential second H2-evolving hydrogenase (Hyd-4) was
      identified in E. coli. In this study the roles of the hyc- and hyf-encoded
      systems in formate-dependent H2 production and Fdh-H activity have been
      investigated. In cells grown on glucose under fermentative conditions at slightly
      acidic pH the production of H2 was mostly Hyd-3- and Fdh-H-dependent, and Fdh-H
      activity was also mainly Hyd-3-dependent. However, at slightly alkaline pH, H2
      production was found to be largely Hyd-4, Fdh-H and F0F1-ATPase-dependent, and
      Fdh-H activity was partially dependent on Hyd-4 and F0F1-ATPase. These results
      suggest that, at slightly alkaline pH, H2 production and Fdh-H activity are
      dependent on both the F0F1-ATPase and a novel FHL, designated FHL-2, which is
      composed of Hyd-4 and Fdh-H, and is driven by a proton gradient established by
      the F0F1-ATPase.

PMID- 11959128
TI  - Agrobacterium tumefaciens supports DNA replication of diverse geminivirus types.
AB  - We have previously shown that the soil-borne plant pathogen Agrobacterium
      tumefaciens supports the replication of tomato leaf curl geminivirus (Australian
      isolate) (TLCV) DNA. However, the reproducibility of this observation with other
      geminiviruses has been questioned. Here, we show that replicative DNA forms of
      three other geminiviruses also accumulate at varying levels in Agrobacterium.
      Geminiviral DNA constructs that lacked the ability to replicate in Agrobacterium
      were rendered replication-competent by changing their configuration so that two
      copies of the viral ori were present. Furthermore, we report that low-level
      replication of TLCV DNA can occur in Escherichia coli containing a dimeric TLCV
      construct in a high copy number plasmid. These findings were reinforced by
      expression studies using beta-glucuronidase which revealed that all six TLCV
      promoters are active in Agrobacterium, and two are functional in E. coli.

PMID- 11959129
TI  - First purification of the antiquitin protein and demonstration of its enzymatic
      activity.
AB  - Antiquitin is an evolutionarily conserved protein believed to play a role in the
      regulation of cellular turgor. Based on sequence analysis, this protein is
      classified as a member of the aldehyde dehydrogenase superfamily. All previous
      studies on antiquitin have been confined to the nucleotide level, and the protein
      has never been purified and characterized. In the present investigation, the
      antiquitin protein was purified for the first time. An acetaldehyde-oxidizing
      protein was isolated from the liver of black seabream (Mylio macrocephalus) by
      chromatographies on alpha-cyanocinnamate Sepharose and Affi-gel Blue agarose,
      followed by ammonium sulfate precipitation. The purified protein was identified
      as antiquitin by the first 18 N-terminal amino acid residues which showed 83.3%
      identity with the deduced sequence of human antiquitin. Electrophoretic mobility
      studies indicated that black seabream antiquitin is a tetramer with a subunit
      molecular mass of 57.5 kDa. Kinetic analysis of the purified protein indicated
      that it catalyzes the oxidation of acetaldehyde with K(m) and V(max) values of
      2.0 mM and 1.3 U/mg, respectively. The longer aliphatic propionaldehyde and the
      aromatic benzaldehyde are also substrates of the purified enzyme. The enzyme is
      highly specific towards NAD+ as the coenzyme and is totally inactive towards
      NADP+. Maximal enzymatic activity was found at about pH 9-10.

PMID- 11959130
TI  - Conventional protein kinase C isoforms regulate human dopamine transporter
      activity in Xenopus oocytes.
AB  - The hypothesis that specific protein kinase C (PKC) isoforms regulate dopamine
      transporter (DAT) function was tested in Xenopus laevis oocytes expressing human
      (h)DAT. Activation of conventional PKCs (cPKCs) and novel PKCs (nPKCs) using 10
      nM phorbol 12-myristate 13-acetate (PMA) significantly inhibited DAT-associated
      transport currents. This effect was reversed by isoform-non-selective PKC
      inhibitors, selective inhibitors of cPKCs and deltaPKC, and by Ca2+ chelation. By
      contrast, the epsilonPKC translocation inhibitor peptide had no effect on PMA
      induced inhibition of hDAT transport-associated currents. Thus, the primary
      mechanism by which PMA regulates hDAT expressed in oocytes appears to be by
      activating cPKC(s).

PMID- 11959132
TI  - A chimera of a gelatinase inhibitor peptide with streptavidin as a bifunctional
      tumor targeting reagent.
AB  - A chimeric protein, consisting of streptavidin fused to a cyclic decapeptide with
      potent inhibitory activity for matrix metalloproteinases (MMP), has been produced
      in Escherichia coli and purified. The purified chimera formed a tetramer and
      showed full biotin-binding ability. The chimera was also capable of both binding
      to MMP-2 and inhibiting its activity. Thus, both the streptavidin moiety and the
      decapeptide of the chimera are fully functional. This bifunctional nature of the
      chimera should facilitate the application of the decapeptide since the
      streptavidin moiety can be used as a specific conjugation site for almost any
      materials upon biotinylation.

PMID- 11959131
TI  - Effect of calcium channel antagonist diltiazem and calcium ionophore A23187 on
      cyclosporine A-induced apoptosis of renal tubular cells.
AB  - Calcium channel antagonists have been reported to have a favorable impact on
      cyclosporin A (CsA)-treated kidney transplant recipients. However, it is not
      clear whether this is because of their direct effect on antagonizing the toxicity
      of CsA to renal tubular cells. In this study, we have used Madin-Darby canine
      kidney tubular cells as a model to examine the effect of diltiazem, a calcium
      channel antagonist, on CsA-induced apoptosis. Moreover, to investigate the
      possible regulation of CsA cytotoxicity by intracellular calcium level, the
      effect of the calcium ionophore A23187 on CsA-induced apoptosis was also
      examined. We found that treatment of CsA (20 microM) alone caused 20-30% cell
      death, which was apparently (30-40%) enhanced by diltiazem at 100 microg/ml,
      accompanied by more severe DNA fragmentation, activation of caspases, and a
      decreased level of Bcl-2. The caspase inhibitor ZVAD-fmk or Bcl-2 overexpression
      was capable of suppressing apoptosis induced by the synergistic effect of
      diltiazem and CsA. Moreover, the survival rate of cells treated with CsA (30
      microM) alone remained only 30%, however, it was markedly (approximately 40%)
      elevated by co-treatment with A23187 (75 ng/ml). The rescue of cells from CsA
      induced apoptosis by A23187 was correlated with AKT activation, BAD
      phosphorylation, and caspase-3 inactivation. Taken together, our results suggest
      that the reported favorable impact of diltiazem on kidney grafts is likely not
      because of its direct protection on renal tubular cells. Instead, it enhances the
      toxicity of CsA to renal tubular cells. In addition, our findings raise a
      possibility that the intracellular calcium level and the AKT pathway may
      participate in the regulation of CsA cytotoxicity.

PMID- 11959133
TI  - Transgene-driven protein expression specific to the intermediate pituitary
      melanotrope cells of Xenopus laevis.
AB  - In the present study, we examined the amphibian Xenopus laevis as a model for
      stable transgenesis and in particular targeted transgene protein expression to
      the melanotrope cells in the intermediate pituitary. For this purpose, we have
      fused a Xenopus proopiomelanocortin (POMC) gene promoter fragment to the gene
      encoding the reporter green fluorescent protein (GFP). The transgene was
      integrated into the Xenopus genome as short concatemers at one to six different
      integration sites and at a total of one to approximately 20 copies. During early
      development the POMC gene promoter fragment gave rise to GFP expression in the
      total prosencephalon, whereas during further development expression became more
      restricted. In free-swimming stage 40 embryos, GFP was found to be primarily
      expressed in the melanotrope cells of the intermediate pituitary.
      Immunohistochemical analysis of cryosections of brains/pituitaries from juvenile
      transgenic frogs revealed the nearly exclusive expression of GFP in the
      intermediate pituitary. Metabolic labelling of intermediate and anterior
      pituitaries showed newly synthesized GFP protein to be indeed primarily expressed
      in the intermediate pituitary cells. Hence, stable Xenopus transgenesis with the
      POMC gene promoter is a powerful tool to study the physiological role of proteins
      in a well-defined neuroendocrine system and close to the in vivo situation.

PMID- 11959134
TI  - A new RNase-based immunoconjugate selectively cytotoxic for ErbB2-overexpressing
      cells.
AB  - We report a new tumor-directed immunoRNase, a chimeric protein made up of an
      antibody fragment (single-chain Fv fragment) directed to ErbB2, a cell surface
      receptor, and a non-toxic, human ribonuclease, which upon cell internalization
      becomes cytotoxic. The immunoRNase is active as a ribonuclease, specifically
      binds and selectively kills ErbB2-positive cells. ErbB2 is one of the most
      specific tumor-associated antigens identified so far, overexpressed on tumor
      cells of different origin. Its choice as target antigen and that of a non-toxic,
      human RNase as the killer moiety makes this immunoRNase a new, potentially
      attractive anticancer agent.

PMID- 11959135
TI  - The nascent polypeptide-associated complex (NAC) promotes interaction of
      ribosomes with the mitochondrial surface in vivo.
AB  - The nascent polypeptide-associated complex (NAC) is a peripheral component of
      cytoplasmic ribosomes, and interacts with nascent chains as they leave the
      ribosome. Yeast mutants lacking NAC translate polypeptides normally, but have
      fewer ribosomes associated with the mitochondrial surface. The mutants lacking
      NAC suffer mitochondrial defects and have decreased levels of proteins like
      fumarase, normally targeted to mitochondria co-translationally. NAC might
      contribute to a ribosomal environment in which amino-terminal, mitochondrial
      targeting sequences can effectively adopt their appropriate conformation.

PMID- 11959136
TI  - Abnormal glycosylation and altered Golgi structure in colorectal cancer:
      dependence on intra-Golgi pH.
AB  - Abnormal glycosylation of cellular glycoconjugates is a common phenotypic change
      in many human tumors. Here, we explore the possibility that an altered Golgi pH
      may also be responsible for these cancer-associated glycosylation abnormalities.
      We show that a mere dissipation of the acidic Golgi pH results both in increased
      expression of some cancer-associated carbohydrate antigens and in structural
      disorganization of the Golgi apparatus in otherwise normally glycosylating cells.
      pH dependence of these alterations was confirmed by showing that an acidification
      defective breast cancer cell line (MCF-7) also displayed a fragmented Golgi
      apparatus, whereas the Golgi apparatus was structurally normal in its
      acidification-competent subline (MCF-7/AdrR). Acidification competence was also
      found to rescue normal glycosylation potential in MCF-7/AdrR cells. Finally, we
      show that abnormal glycosylation is also accompanied by similar structural
      disorganization and fragmentation of the Golgi apparatus in colorectal cancer
      cells in vitro and in vivo. These results suggest that an inappropriate Golgi pH
      may indeed be responsible for the abnormal Golgi structure and lowered
      glycosylation potential of the Golgi apparatus in malignant cells.

PMID- 11959137
TI  - Blue light specific and differential expression of a plastid sigma factor, Sig5
      in Arabidopsis thaliana.
AB  - The transcription of plastid gene psbD is under the control of the BLRP (blue
      light-responsive promoter) recognized by plastid-encoded RNA polymerase, in which
      nuclear-encoded sigma factors play a crucial role in the promoter recognition. We
      examined the effects of light on mRNA levels of six different SIG genes in
      Arabidopsis and found that blue light extensively induced the accumulation of
      SIG5 transcripts, but red light did not. The blue light specificity was not
      observed in the accumulations of remaining five SIG genes. The blue light
      dependency of the SIG5 expression well explains the light-dependent behavior of
      the psbD BLRP.

PMID- 11959138
TI  - Ca(v)2.3 (alpha1E) Ca2+ channel participates in the control of sperm function.
AB  - To know the function of the Ca2+ channel containing alpha(1)2.3 (alpha1E) subunit
      (Ca(v)2.3 channel) in spermatozoa, we analyzed Ca2+ transients and sperm motility
      using a mouse strain lacking Ca(v)2.3 channel. The averaged rising rates of Ca2+
      transients induced by alpha-D-mannose-bovine serum albumin in the head region of
      Ca(v)2.3-/- sperm were significantly lower than those of Ca(v)2.3+/+ sperm. A
      computer-assisted sperm motility assay revealed that straight-line velocity and
      linearity were greater in Ca(v)2.3-/- sperm than those in Ca(v)2.3+/+ sperm.
      These results suggest that the Ca(v)2.3 channel plays some roles in Ca2+
      transients and the control of flagellar movement.

PMID- 11959140
TI  - Crystal structure of human nicotinamide mononucleotide adenylyltransferase in
      complex with NMN.
AB  - The final step in the biosynthesis of nicotinamide-adenine dinucleotide, a major
      coenzyme in cellular redox reactions and involved in intracellular signaling, is
      catalyzed by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT).
      The X-ray structure of human NMNAT in complex with nicotinamide mononucleotide
      was solved by the single-wavelength anomalous dispersion method at a resolution
      of 2.9 A. Human NMNAT is a symmetric hexamer whose subunit is formed by a large
      six-stranded parallel beta-sheet with helices on both sides. Human NMNAT displays
      a different oligomerization compared to the archaeal enzyme. The protein
      nicotinamide mononucleotide interaction pattern provides insight into ligand
      binding in the human enzyme.

PMID- 11959139
TI  - Der f 16: a novel gelsolin-related molecule identified as an allergen from the
      house dust mite, Dermatophagoides farinae.
AB  - Allergen from the house dust mite (Dermatophagoides sp.) is a major trigger
      factor of allergic disorders, and its characterization is crucial for the
      development of specific diagnosis or immunotherapy. Here we report the
      identification of a novel dust mite (Dermatophagoides farinae) antigen whose
      primary structure belongs to the gelsolin family, a group of actin cytoskeleton
      regulatory proteins. Isolated mite cDNA, termed Der f 16, encodes 480 amino acids
      comprising a four-repeated gelsolin-like segmental structure, which is not seen
      in conventional gelsolin family members. Enzyme immunoassay indicated that
      recombinant Der f 16 protein, prepared using an Escherichia coli expression
      system, bound IgE from mite-allergic patients at 47% (8/17) frequency. This is
      the first evidence that the gelsolin family represents a new class of allergen
      recognizable by atopic patient IgE.

PMID- 11959141
TI  - Trans-translation mediated by Bacillus subtilis tmRNA.
AB  - Trans-translation, in which a ribosome switches between translation of an mRNA
      and a tmRNA, produces a chimera polypeptide of an N-terminal truncated
      polypeptide and a C-terminal tag-peptide encoded by tmRNA. One of the tmRNA
      binding proteins, a ribosomal protein S1, has not been found in a group of Gram
      positive bacteria. In this study, the trans-translation reaction with tmRNA from
      Bacillus subtilis belonging to this group was examined. When a truncated gene
      lacking a termination codon was expressed in B. subtilis, a 15-amino acid tag
      peptide derived from tmRNA was identified in the C-termini of the trans
      translation products. An identical tag-peptide was also found at the C-termini of
      the products from a truncated gene, when it was coexpressed with B. subtilis
      tmRNA in Escherichia coli. B. subtilis tmRNA was functional, although much less
      efficiently, in the in vitro poly(U)-dependent tag-peptide synthesis system of E.
      coli. A comparison of two bacterial tmRNAs suggests that the rule for determining
      the tag-initiation point on tmRNA may be the same in Gram-positive and Gram
      negative bacteria.

PMID- 11959142
TI  - False positive non-synonymous polymorphisms of G-protein coupled receptor genes.
AB  - Polymorphisms of G-protein coupled receptor (GPCR) genes are associated with
      disease risk and modification, and the response to receptor-directed therapy.
      Genomic sequencing ( approximately 1700 automated runs) from as many as 120
      chromosomes from 60 multiethnic individuals was performed to confirm non
      synonymous coding polymorphisms reported in the dbSNP database from 25 randomly
      selected GPCR genes. These polymorphisms were in regions of the receptors
      responsible for structural integrity, ligand binding, G-protein coupling and
      phosphoregulation. However, most of these putative polymorphisms could not be
      confirmed (false positive rate of 68%). Based on these results, we suggest that
      the variability of the superfamily is not well defined, and we caution against
      exclusive reliance on databases for selection of candidate GPCR polymorphisms for
      disease association and pharmacogenetic studies.

PMID- 11959143
TI  - NF-kappaB activation upon interaction of HIV-1 envelope glycoproteins with cell
      surface CD4 involves IkappaB kinases.
AB  - Human immunodeficiency virus type-1 envelope glycoprotein (gp120(env)) binding to
      cell surface CD4 receptor triggers a broad range of intracellular effects leading
      to T cell activation and cell cycle entry. Among these effects we and others
      previously reported on the nuclear translocation of the nuclear factor-kappaB (NF
      kappaB) transcription factor. The present work further investigates the signal
      transduction pathways involved in gp120(env)-induced NF-kappaB activation. We
      demonstrate that gp120(env)-CD4 interaction stimulates the hyperphosphorylation
      of IkappaB-alpha inhibitory protein. Conversely, overexpression of a dominant
      negative IkappaB-alpha transgene mutated at S32 and S36 residues, abolishes
      gp120(env)-induced NF-kappaB activation. IkappaB kinases (IKKs) activity was
      found to be selectively enhanced following CD4 engagement with gp120(env) and to
      mediate the phosphorylation of IkappaB-alpha while co-transfection experiments
      using dominant-negative forms of IKKs inhibited gp120(env)-induced NF-kappaB
      activation. Taken together, these results confirm that IKKs complex play a key
      role in gp120(env)-induced NF-kappaB activation.

PMID- 11959144
TI  - Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by
      nucleotides.
AB  - The protein phosphatases PP1(c), PP2A(c) and PP2Calpha are shown to
      dephosphorylate protein kinase Cdelta (PKCdelta) in vitro; of these PP2A(c)
      displayed the highest specific activity towards PKCdelta. The role of PP2A(c) in
      the dephosphorylation of PKCdelta in cells was supported by the demonstration
      that these proteins could be co-immunoprecipitated from NIH3T3 cells. However the
      observation that binding of Mg-ATP to PKCdelta could protect the enzyme from
      dephosphorylation by PP2A(c) in vitro indicates that an additional input/factor
      is required for dephosphorylation in vivo.

PMID- 11959145
TI  - The calcium-binding EF-hand in polycystin-L is not a domain for channel
      activation and ensuing inactivation.
AB  - Polycystin-L (PCL) shares high homology with polycystin-2, the product of
      polycystic kidney disease gene-2. It was previously shown that the PCL forms a
      non-selective cation channel activated by calcium influx. However, it remains
      unclear whether calcium activates/inactivates PCL by binding to the EF-hand motif
      located on the cytoplasmic carboxyl-terminus. Here we obtained two PCL splice
      variants from liver (PCL-LV, lacking the EF-hand) and testis (PCL-TS, lacking 45
      amino acids on the carboxyl tail) using PCR-based approaches. When expressed in
      Xenopus oocytes and studied using electrophysiology both splice variants
      exhibited basal cation channel activity and calcium-induced channel activation.
      While PCL-TS displayed similar activation to PCL, PCL-LV exhibited a three-fold
      increased activation. All five PCL C-terminal artificial truncation mutants also
      exhibited basal and calcium-activated channel activities, in particular the
      mutant T622X lacking the EF-hand was associated with increased activation. Our
      data demonstrate that the EF-hand and other parts of the carboxyl tail of PCL are
      not determinants of channel activation/inactivation although the EF-hand seems to
      be involved in the modulation of these processes.

PMID- 11959147
TI  - Relationship between hydrogen-bonding network and reduction potential in c-type
      cytochromes.

PMID- 11959146
TI  - CLK-1 protein has DNA binding activity specific to O(L) region of mitochondrial
      DNA.
AB  - Mutations in the clk-1 gene of Caenorhabditis elegans extend worm life span and
      slow down a variety of physiological processes. Here we report that C. elegans
      CLK-1 as well as its mouse homologue have DNA binding activity that is specific
      to the O(L) region of mitochondrial DNA. DNA binding activity of CLK-1 is
      inhibited by ADP, and is altered by mutations that extend nematode life span. Our
      results suggest that, in addition to its enzymatic function in ubiquinone
      biosynthesis, CLK-1 is involved in the regulation of mtDNA replication or
      transcription.

PMID- 11959149
TI  - Sialosyl-galactose: a common denominator of Guillain-Barre and related disorders?
AB  - The immune reactivity implicated in the pathogenesis of Guillain-Barre syndrome
      (GBS) and related diseases, which occur following infection with specific strains
      of Campylobacter jejuni bearing sialylated lipopolysaccharide structures that
      cross-react with specific gangliosides, is consistent with provocation of
      inflammation via molecular mimicry. In this review, we have focused upon
      microbial characteristics and structures, the fine structure of the essential
      carbohydrate determinants, and the application of our proposed criteria, modified
      from those of Koch for causation of infectious and of Witebsky for autoimmune
      diseases, to the circumstance of infectious induction of autoimmune disorder.

PMID- 11959150
TI  - Very early activation of m-calpain in peripheral nerve during Wallerian
      degeneration.
AB  - Peripheral nerve injury results in a series of events culminating in degradation
      of the axonal cytoskeleton (Wallerian degeneration). In the time period between
      axotomy and cytoskeletal degradation (24-48 h in rodents), there is calcium entry
      and activation of calpains within the axon. The precise timing of these events
      during this period is unknown. In the present study, antibodies were generated to
      three distinct peptide epitopes of m-calpain, and a fusion protein antibody was
      generated to the intrinsic calpain inhibitor calpastatin. These antibodies were
      used to measure changes in these proteins in mouse sciatic nerves during
      Wallerian degeneration. In sciatic nerve homogenates and cultured dorsal root
      ganglion (DRG) neurites, m-calpain protein was significantly reduced in
      transected nerves very early after nerve injury, long before axonal degeneration
      occurred. Levels of m-calpain protein remained low as compared to control nerves
      for the remainder of the 72-h time course. No changes in calpastatin protein were
      evident. Systemic treatment of animals with the protease inhibitor leupeptin
      partially prevented the rapid loss of calpain protein. Removal of calcium in DRG
      cultures had the same effect. These data indicate that m-calpain protein is lost
      very early after axonal injury, and likely reflect activation and degradation of
      this protein long before the cytoskeleton is degraded. Calpain activation may be
      an early event in a proteolytic cascade that is initiated by axonal injury and
      culminates with axonal degeneration.

PMID- 11959151
TI  - Up-regulation of interleukin-12 receptor expression in peripheral blood
      mononuclear cells of patients with HTLV-I-associated myelopathy/tropical spastic
      paraparesis.
AB  - We previously reported elevated levels of serum interleukin-12 (IL-12) in
      association with increased interferon-gamma (IFN-gamma) levels in patients with
      human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP). The interaction between IL-12 and IL-12 receptor (IL-12R)
      plays an important role in differentiation of the T helper type 1 (Th1)
      phenotype. In this study, we further examined the IL-12/IL-12R axis by
      investigating the expression of IL-12R and CD40 ligand (CD40L) in peripheral
      blood mononuclear cells (PBMC) of 18 HAM/TSP patients, and comparing the levels
      with those in 25 patients with other neurological disorders, including 4 anti
      HTLV-I-seropositive carriers as controls. Two-color analysis by flow cytometry
      revealed a significantly high percentage of IL-12R beta1+ cells in CD4+ T
      lymphocytes in HAM/TSP patients compared to the control. Furthermore, IL-12R
      beta2 mRNA expression in PBMC was detected by reverse-transcriptase polymerase
      chain reaction in 6 of 18 HAM/TSP patients, but not in any control patients. In
      contrast, there was no significant difference between the percentage of CD40L+
      cells in CD4+ T lymphocytes in HAM/TSP and control patients. Our results suggest
      Th1 immune activation in patients with HAM/TSP, which leads to chronic
      inflammation in the spinal cord, mediated by dysregulation of the IL-12/IL-12R
      axis rather than of the CD40/CD40L interaction.

PMID- 11959152
TI  - Hypercortisolemia in acute stroke is related to the inflammatory response.
AB  - Hypercortisolemia is thought to be a marker of the stress response following
      stroke. The aim of this study was to investigate the prevalence and prognostic
      significance of hypercortisolemia. The circadian variation of cortisol level and
      the relationship between serum cortisol levels and other stress, inflammatory,
      and haemostatic markers were also investigated. Seventy consecutive patients with
      their first ischemic stroke and 24 age- and sex-matched controls were included in
      the study. Serum cortisol levels (at 6:00 AM, 10:00 AM, 6:00 PM, and 10:00 PM),
      24-h urine catecholamine excretion, beta-thromboglobulin levels, and other
      standard biochemical and haematological parameters were measured on the first day
      of hospitalisation and in control subjects. Outcome measures used the Barthel
      Index at Day 30, as well as 30- and 90-day mortality rates. Hypercortisolemia,
      defined as at least two of the four measurements above the normal range of serum
      cortisol levels (i.e. >618 nmol/l from the morning samples and >460 nmol/l from
      the evening samples) was found in 25 (35.7%) of the acute stroke patients and in
      3 (12.5%) of the controls (p<0.05). Hypercortisolemia was associated with older
      age, greater severity of neurological deficit, larger ischemic lesions on CT, and
      worse prognoses (p<0.05). The study did not find a correlation between serum
      cortisol levels and other markers of the stress response such as catecholamines
      excretion and glucose levels. A significant correlation between serum cortisol
      levels and some markers of the inflammatory response, such as fever, fibrinogen
      level, white blood cell (WBC) count, and beta-thromboglobulin level, was
      established in stroke patients. Prognostic significance of hypercortisolemia in
      acute stroke patients seems to be related to the inflammatory response rather
      than to the stress response.

PMID- 11959153
TI  - Restless legs syndrome in Parkinson's disease.
AB  - INTRODUCTION: Recent clinical and functional imaging data suggest impaired
      central dopaminergic transmission in restless legs syndrome (RLS). As RLS
      responds to dopaminergic medications, an etiologic link between RLS and
      Parkinson's disease (PD) has been proposed. However, few studies have examined
      this association. OBJECTIVE: To investigate the prevalence of RLS amongst PD
      outpatient population. METHOD: The prevalence of RLS was determined by the
      diagnostic criteria of the International Restless Legs Syndrome Study Group
      (IRLSSG). Consecutive PD patients (n=125) were prospectively evaluated in our
      clinic. RESULTS: There were 77 (61.6%) males and 48 (38.4%) females with a mean
      age of 65.1+/-9.3 (SD) years (range 34-83), and mean age of onset of disease at
      59.6 years+/-10.7 (SD) years (range 30-81). Nineteen (15.2%) patients had motor
      restlessness. Of these, one (0.8%) patient had RLS-like symptoms closely
      correlated to wearing "off" effect of levodopa. None of the patients satisfied
      the IRLSSG diagnostic criteria of RLS. This was not significantly different
      compared to the 0.6% and 0.1% RLS prevalence in our general population and clinic
      population. CONCLUSIONS: Our study demonstrates that motor restlessness was
      present in 15.2% of our PD patients. However, prevalence of RLS in our PD
      patients was not significantly different from our general population or clinic
      population, suggesting that these two diseases may not share the same
      pathophysiologic mechanism.

PMID- 11959154
TI  - Diffusion MRI in three types of anoxic encephalopathy.
AB  - We report the clinical and diffusion-weighted MRI (DWI) features of three
      patients with different types of anoxic brain injury: attempted hanging (hypoxic
      hypoxia), carbon monoxide poisoning (histotoxic hypoxia), and hanging with
      cardiac arrest (hypoxic-ischemic encephalopathy, HIE). The first two patients,
      but not the third, recovered substantial neurological function. The distribution
      of DWI abnormalities was different and correlated well with the distinct
      neuropathological features of these entities. The prognosis after anoxic
      encephalopathy depends on the underlying mechanism and its severity, which may be
      reflected by DWI abnormalities.

PMID- 11959155
TI  - Detection of anti-ganglioside antibodies in Guillain-Barre syndrome and its
      variants by the agglutination assay.
AB  - Sera from 40 patients with Guillain-Barre syndrome (GBS), including the subtypes
      acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal
      neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller
      Fisher syndrome (MFS) were examined for the presence of anti-ganglioside
      antibodies using the ganglioside agglutination assay, and the enzyme-linked
      immunosorbent assay (ELISA). In the ELISA system, sera were tested for IgM and
      IgG antibodies to GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides. Antibodies
      to gangliosides were detected in 21 (53%) of the GBS patients by agglutination
      assay and in 17 (43%) of the patients by ELISA. Some of the sera reacted with
      more than one ganglioside. Antibodies were not found in the control sera that
      were studied. The agglutination assay may be useful for rapid screening of GBS
      sera for antibodies to multiple gangliosides.

PMID- 11959156
TI  - Scavenger receptor class B type I expression and elemental analysis in cerebellum
      and parietal cortex regions of the Alzheimer's disease brain.
AB  - Metal ions play an important role in health and disease by influencing cellular
      biochemical pathways. The increased concentrations of some metal ions may have
      cytotoxic effects through their ability to oxidatively modify biomolecules, which
      may cause oxidative stress-induced brain cell death leading to neurodegenerative
      disorders observed in Alzheimer's disease (AD). We therefore performed elemental
      analysis of human brain tissues by a sophisticated method of inductively coupled
      plasma mass spectrometry (ICP-MS) in two regions of the AD brain, the parietal
      cortex and cerebellum, and compared them with the age-matched control. Our
      analysis shows the differential distribution of some metal ions in the two
      regions of the brain. Most importantly, Si, Sn, Al and Mn showed significantly
      higher levels in the parietal cortex of the AD brain compared to the control. The
      other metal ions showing moderate increases in the parietal cortex were Na, Te,
      Cr, Fe and B. Since these metal ions can modify lipoproteins in the brain and
      modified lipoproteins are taken up by scavenger receptors class B type I (SR-BI),
      we also determined the presence of SR-BI in the parietal cortex and cerebellum
      regions of the control and AD brains using a sensitive method, the reverse
      transcriptase-polymerase chain reaction. Our results suggest that SR-BI are
      present in the parietal cortex as well as in the cerebellum of the control and AD
      brains, suggesting that the presence of SR-BI may be involved in the uptake of
      oxidatively modified lipoproteins and beta-amyloid (Abeta) protein complexed with
      apoE, suggesting implications in the progression of late onset AD and other
      neurodegenerative disorders characterized by the deposition of insoluble
      aggregates observed in the AD brain.

PMID- 11959157
TI  - Cytoskeleton abnormalities in axonopathies of unknown aetiology: correlations
      with morphometry.
AB  - To determine if specific axonal cytoskeleton abnormalities could be demonstrated
      in axonopathies without aetiology, nerve biopsies from five controls and nine
      cases were analyzed by morphometry and immunocytochemistry with anti
      neurofilament (NF, subunits L, M, H) and anti-beta tubulin (TUB) antibodies.
      Morphometry revealed either large fiber atrophy (decrease in large fiber density
      with increased density in small fibers), degeneration of large fibers (decrease
      in large fiber density and in total density of fibers) or of all diameter fibers.
      NF immunostaining density decreased (by 21-89%) only in cases with fiber loss, in
      parallel to myelinated fiber density as determined by morphometry. On the
      contrary, the density of fibers labelled for TUB increased significantly in all
      except two cases by 52-102% over controls. Nevertheless, in these two cases--with
      a severe loss of fibers--as well as in other cases, the ratio of the density of
      fibers labelled for TUB and NFL (TUB/NFL) increased by 48-404%. Thus, the total
      density of myelinated fibers was always inversely correlated with the TUB/NFL
      ratio. Similar abnormalities have been described only after axotomy; our cases
      could thus be compared to <<permanent axotomy>>.

PMID- 11959158
TI  - Subtype analysis of neuropathologically diagnosed patients in a Japanese
      geriatric hospital.
AB  - Dementia is a social problem in Japan, as it is in other countries. Recently,
      there has been an increase in the number of patients with Alzheimer-type dementia
      (ATD) in the population. We analyzed 239 cases of patients autopsied at
      Fukushimura Hospital over a 10-year period. Clinicopathologically, 66% of these
      cases (158 cases) presented with dementia symptoms. The predominant form of
      illness was ATD. We found dementia with Lewy bodies (DLB) to be as frequent as
      vascular dementia (VD). Although the numbers were small, limbic neurofibrillary
      tangle dementia (LNTD) and Pick's disease (PiD) followed a clinical course
      typical of these diseases. On the other hand, senile dementia of the Alzheimer's
      type (SDAT) and the common form of neocortical type DLB (diffuse Lewy body
      disease; DLBD) were difficult to distinguish from each other. We attempted to
      uncover differences between these dementias in terms of how they affect male and
      female patients. The clinical course of the male patients with the common form of
      neocortical type DLB was more or less typical, while that of the female patients
      was not.

PMID- 11959159
TI  - Severe involvement of the ambient gyrus in a case of dementia with argyrophilic
      grain disease.
AB  - We report here the severe involvement of the ambient gyrus in a case of
      argyrophilic grain (AG) dementia (AGD). The patient was a 78-year-old man who was
      first presented with prosopagnosia (agnosia of the face) at age 68, which was
      followed by progressive mental decline and the patient's death in a state of
      tetraplegia. The postmortem study showed severe atrophy of the medial temporal
      lobe with anterior gradient, most prominent in the ambient gyrus. Histologically,
      numerous AGs, pretangles and coiled bodies were detected by Gallyas-Braak (G-B)
      silver staining and also by immunostaining with various anti-tau antibodies in
      the affected area. Tau-immunoreactive ballooned neurons were also present.
      Neuronal loss and gliosis with laminar sponginess were evident in the ambient
      gyrus. Diffuse plaques were seen in the neocortex and frequently associated with
      clusters of AGs, which were morphologically distinct from neuritic plaques.
      Neurofibrillary tangles were localized in the entorhinal area. Vascular lesions
      were very scanty. Thus, this case fulfilled the morphological criteria of AGD. It
      is still unclear whether AG itself causes neuronal degeneration leading to
      dementia. The present case may reflect the importance of the ambient gyrus in the
      center of neuronal degeneration in AGD.

PMID- 11959161
TI  - Cold pressor test demonstrates residual sympathetic cardiovascular activation in
      familial dysautonomia.
AB  - In familial dysautonomia (FD), i.e. Riley-Day-syndrome, sympathetic
      cardiovascular function, as well as afferent temperature and pain mediating
      neurons, are significantly reduced. Thus, it was questioned if cold pressor test
      (CPT), which normally enhances sympathetic outflow and induces peripheral
      vasoconstriction by the activation of thermo- and nociceptive system activation,
      could be used to assess sympathetic function in FD. To evaluate whether CPT can
      be used to assess sympathetic activation in FD, we performed CPT in 15 FD
      patients and 18 controls. After a 35-min resting period, participants immersed
      their right hand and arm up to the elbow into 0-1 degrees C cold water while we
      monitored heart rate (HR), respiration, beat-to-beat radial artery blood pressure
      (BP), and laser Doppler skin blood flow (SBF) at the right index finger pulp.
      From these measurements, heart rate variability parameters were calculated: root
      mean square of successive differences (RMSSD), coefficient of variation (CV), low
      and high frequency (LF, HF) power spectra of the electrocardiogram (ECG). All
      participants perceived cold stimulation and indicated discomfort. In controls,
      SBF decreased and HR and BP increased rapidly upon CPT. After 60 s, SBF indicated
      secondary vasodilatation in six controls, BP rise attenuated and HR returned to
      baseline in all controls. In the patients, SBF remained unchanged, HR and BP
      increased significantly, but after 50-60 s of CPT and changes were lower than in
      controls (p<0.05). RMSSD and CV decreased and LF increased significantly only in
      the controls. We conclude that CPT activates sympathetic HR and BP modulation
      despite impaired pain and temperature perception in FD patients. BP increase in
      the presence of almost unchanged SBF might be due to HR increase and to
      nociceptive arousal and emotionally induced catecholamine release as seen in
      emotional crises of FD patients. CPT assesses sympathetic cardiovascular
      responses independently from baroreflex function, which is compromised in FD.

PMID- 11959160
TI  - Neurotologic manifestations of the fibromyalgia syndrome.
AB  - The purpose was to assess otologic symptoms, and audiologic and vestibular
      findings in fibromyalgia (FM) syndrome. Twenty-four female patients with FM
      syndrome (FMS) were included in the study. The assessments were based on history,
      physical examination, audiometry, bithermal caloric testing and auditory
      brainstem response (ABR) testing. Dizziness was the most common complaint of the
      patients, and was followed by tinnitus, hearing loss and vertigo. Almost 50% of
      the patients had some sort of otologic symptoms.Dix-Halpike maneuver proved
      positional rotary vertigo in 5 (20.8%) patients. The audiometry results of 23
      patients were normal. None of the patients had abnormal bithermal caloric
      testing. Although there were a variety of ABR abnormalities, the ABR results of
      the patients with and without cochleovestibular symptoms were not significantly
      different (p<0.05). In conclusion, FM patients can complain otologic symptoms
      even though they do not have any clinically or audiologically detectable ear
      disease. A neural disintegration or some other events related to neural mediators
      may be the mechanisms involved in the pathogenesis of otoneurologic as well as
      systemic manifestations of the disease that possibly leads to abnormal perception
      of the stimuli coming from internal or external environment.

PMID- 11959162
TI  - Cerebral cavernous malformation: novel mutation in a Chinese family and evidence
      for heterogeneity.
AB  - Familial cerebral cavernous malformation (CCM) is an autosomal dominant disorder
      producing vascular anomalies throughout the central nervous system associated
      with seizures and hemorrhagic stroke. Linkage analysis has shown evidence for at
      least three genetic loci underlying this disorder with a founder mutation in the
      Mexican/Hispanic community. We report the first family of Chinese ethnic origin
      with CCM having a novel mutation in the CCM1 gene. The mutation in exon 19 causes
      a premature stop codon (Q698X) predicted to produce a truncated Krev1 interaction
      trapped 1 (KRIT1) protein. Members of the family with this mutation have a wide
      range in age of onset with seizures, ataxia, spinal cord vascular malformation,
      headaches and skin lesions. An additional unrelated sporadic subject with brain
      lesions compatible with CCM as well as vascular skin findings suggesting the blue
      rubber bleb nevus (BRBN) syndrome has no mutation detected in the CCM1 gene.
      These findings expand the phenotype of and demonstrate further evidence for the
      heterogeneity in the CCM syndrome.

PMID- 11959163
TI  - Fortifying our monument amidst the changing landscape of transplantology.

PMID- 11959164
TI  - Identification of subarachnoid hemorrhages with high risk of evolution to brain
      death.

PMID- 11959166
TI  - Risk factors associated with diabetes insipidus in brain dead patients.

PMID- 11959165
TI  - Apnea test in diagnosis of brain death: comparison of two methods and analysis of
      complications.

PMID- 11959167
TI  - Influence of expanding donor age on the allocation of kidneys for
      transplantation.

PMID- 11959168
TI  - Review of cadaveric kidney donation programme at Manchester Royal Infirmary.

PMID- 11959169
TI  - Timing comparison of donation process after the new real decreto of
      transplantation in Spain.

PMID- 11959170
TI  - Experience with transplant coordination in northern Mexico following the Spanish
      model.

PMID- 11959171
TI  - The medical-nursing team specialized in the maintenance of the brain-dead heart
      beating organ donor exclusively dedicated to caring for the donor reduces donor
      loss from asystolia to zero.

PMID- 11959172
TI  - Organ donation interviews in community of Madrid, Spain.

PMID- 11959173
TI  - Introducing an informative program on donation and transplantation into secondary
      education.

PMID- 11959174
TI  - Training course on donation and transplantation for 16- to 18-year-old
      schoolchildren in the Hospital de Sant Pau.

PMID- 11959175
TI  - Quality control of cornea procurement and distribution for transplantation.

PMID- 11959176
TI  - Gene therapy in organ transplantation.

PMID- 11959177
TI  - Mycophenolate mofetil aggravates postischemic acute renal failure in rats.

PMID- 11959178
TI  - Nitric oxide in cold and warm ischemia reperfusion renal transplantation.

PMID- 11959179
TI  - The ether phospholipids trail: blood timing in renal ischemia-reperfusion injury.

PMID- 11959180
TI  - Prospective comparative study of the efficacy of Celsior solution for
      preservation in clinical liver transplant.

PMID- 11959182
TI  - Comparison of UW and Celsior solutions in experimental liver preservation by
      assessment of alpha-glutathione sulfotransferase.

PMID- 11959181
TI  - Effect of the platelet-activating factor antagonist BN-52021 on liver
      preservation (4 degrees): experimental study in isolated reperfused rat liver
      model.

PMID- 11959183
TI  - Comparative study of Celsior and Belzer solutions for hepatic graft preservation:
      preliminary results.

PMID- 11959184
TI  - Effects of urodilatin on renal graft blood flow during ischemia-reperfusion
      syndrome in a pig autotransplant model.

PMID- 11959185
TI  - Is there any risk of transmission of hepatitis B from heart donors hepatitis B
      core antibody positive?

PMID- 11959186
TI  - Clinical management of renal transplant patients with hepatitis C virus infection
      treated with cyclosporine or tacrolimus.

PMID- 11959187
TI  - Association between cytomegalovirus antigenemia and hepatitis C virus-RNA in HCV
      seropositive renal transplants.

PMID- 11959188
TI  - Use of cytomegalovirus antigenemia as a marker for preemptive treatment.

PMID- 11959189
TI  - Prevention of cytomegalovirus disease after heart transplantation: preemptive
      therapy with 7 days' intravenous ganciclovir.

PMID- 11959190
TI  - Epstein-Barr virus reactivation in kidney transplant recipients: relevance of
      serologic study.

PMID- 11959191
TI  - Prophylaxis of cytomegalovirus disease with ganciclovir or anti-CMV
      immunoglobulin in renal transplant recipients who receive antilymphocytic
      antibodies as induction therapy.

PMID- 11959192
TI  - Association between human herpesvirus type 6 and type 7, and cytomegalovirus
      disease in heart transplant recipients.

PMID- 11959193
TI  - Prevalence of past varicella zoster virus infection in candidates for kidney
      transplantation: vaccination in seronegative patients.

PMID- 11959194
TI  - Increased frequency of tuberculosis in Mexican renal transplant recipients: a
      single-center experience.

PMID- 11959195
TI  - Prophylaxis with oral fluconazole and an oral solution of amphotericin B in liver
      transplant patients.

PMID- 11959196
TI  - Treatment of mucor infection after liver or pancreas-kidney transplantation.

PMID- 11959197
TI  - Immunosuppression using tacrolimus/mycophenolate versus neoral/mycophenolate
      following kidney transplantation: a single-center experience.

PMID- 11959198
TI  - Simple tacrolimus-based immunosuppressive regimens following renal
      transplantation: a large multicenter comparison between double and triple
      therapy.

PMID- 11959199
TI  - Early cyclosporine a withdrawal in kidney transplant recipients under a sirolimus
      based immunosuppressive regimen: pathological study of graft biopsies at 1-year
      posttransplant.

PMID- 11959200
TI  - One-center comparison between primary immunosuppression based on neoral
      cyclosporine and tacrolimus for renal transplantation.

PMID- 11959201
TI  - Role of immunosuppressive treatments based on mycophenolate mofetil in
      posttransplantation renal surgical complications.

PMID- 11959202
TI  - Mycophenolate mofetil immunosuppressive therapies increase the incidence of
      cytomegalovirus infection in renal transplantation.

PMID- 11959203
TI  - Results of a triple induction regime with tacrolimus, mycophenolate mofetil, and
      prednisone in renal transplantation.

PMID- 11959204
TI  - Immunosuppression with sirolimus, cyclosporyne, and prednisone in renal
      transplantation.

PMID- 11959206
TI  - Efficacy and safety of basiliximab in pediatric renal transplantation.

PMID- 11959205
TI  - Experience with basiliximab in pediatric renal transplantation.

PMID- 11959207
TI  - Use of reduced dose of OKT3 (2.5 mg) after renal transplantation.

PMID- 11959208
TI  - Experience with tacrolimus as primary immunosuppressor in pediatric liver
      transplant.

PMID- 11959209
TI  - Immunosuppression with calcineurin inhibitors and polyclonal antibodies in liver
      transplantation.

PMID- 11959210
TI  - Prospective evaluation of a quadruple therapy based on tacrolimus after liver
      transplantation.

PMID- 11959211
TI  - Selective immunosuppression with daclizumab in liver transplantation with graft
      versus-host disease.

PMID- 11959212
TI  - Late xenograft rejection: comparison between liver and heart xenografts under low
      dose tacrolimus.

PMID- 11959213
TI  - Replacement of cyclosporine by tacrolimus for immunosuppression in heart
      transplant patients: safety and efficacy.

PMID- 11959214
TI  - Histopathological findings in heart transplant patients under tacrolimus
      mycophenolate mofetil versus cyclosporine microemulsion-azathioprine.

PMID- 11959215
TI  - Low-dose oral prednisone in the treatment of acute cardiac allograft rejection.

PMID- 11959216
TI  - Steroids withdrawal after 3 months of successful renal transplantation using a
      tacrolimus- and mycophenolate-based immunosuppression.

PMID- 11959217
TI  - Monotherapy with tacrolimus and corticosteroid withdrawal.

PMID- 11959218
TI  - De novo diabetes in solid organ transplantation.

PMID- 11959220
TI  - Arterial hypertension.

PMID- 11959219
TI  - Dyslipemia and long-term immunosuppression.

PMID- 11959221
TI  - The limitations of calcineurin and mTOR inhibitors: new directions for
      immunosuppressive strategies.

PMID- 11959222
TI  - Analysis of the adverse effects of immunosuppressive therapy in heart
      transplantation.

PMID- 11959223
TI  - Reduction in blood cyclosporine concentration by orlistat in two renal transplant
      patients.

PMID- 11959224
TI  - Predictive value of cyclosporine blood levels during the absorption phase to
      estimate the area under the curve in stable renal transplant patients.

PMID- 11959225
TI  - Tacrolimus pharmacokinetics in heart transplant.

PMID- 11959226
TI  - Use of mycophenolate mofetil in patients with transplanted heart and renal
      insufficiency: the relevance of the pharmacokinetic study.

PMID- 11959227
TI  - Preliminary results of rescue therapy with tacrolimus and mycophenolate mofetil
      in lung transplanted patients with bronchiolitis obliterans.

PMID- 11959228
TI  - Factors associated with early and late mortality following heart transplantation:
      Spanish Registry of Heart Transplantation 1984 to 1999.

PMID- 11959229
TI  - Sensitivity and specificity of clinical variables in the diagnosis of heart
      transplant rejection.

PMID- 11959230
TI  - Combined dialitic therapy in the treatment of vascular rejection after heart
      transplantation.

PMID- 11959231
TI  - Microchimerism after heart transplantation: prevalence, predisposing factors,
      natural history, and prognosis.

PMID- 11959233
TI  - Pulmonary hypertension and right ventricular failure after heart transplantation:
      usefulness of nitric oxide.

PMID- 11959232
TI  - Steroid withdrawal in nonimmunologically selected heart transplant recipients.

PMID- 11959234
TI  - Value of QT dispersion analysis for noninvasive detection of cardiac allograft
      rejection.

PMID- 11959235
TI  - Echocardiographic backscatter signal analysis in heart transplant: is it useful
      in characterizing hypertrophy?

PMID- 11959236
TI  - The value of brain natriuretic peptide for the diagnosis of heart transplant
      rejection.

PMID- 11959237
TI  - The value of oxygen consumption in the prognosis of ambulatory patients suffering
      from chronic heart failure: its relevance in heart transplantation.

PMID- 11959238
TI  - Effect of carvedilol therapy on functional mitral regurgitation, ventricular
      remodeling, and contractility in patients with heart failure due to left
      ventricular systolic dysfunction.

PMID- 11959240
TI  - Assessment of the effectiveness of descending aortomyoplasty for nonischemic
      cardiac failure using the subendocardial viability index.

PMID- 11959239
TI  - Lipid-lowering effect of atorvastatin in heart transplantation.

PMID- 11959241
TI  - Experimental treatment with beta blockers of hemodynamic and myocardial changes
      in organ donors.

PMID- 11959242
TI  - Coronary angiography in patients undergoing evaluation for lung transplantation.

PMID- 11959243
TI  - Human islet isolation in fresh pancreas or after preservation in UW solution.

PMID- 11959244
TI  - Isolation and in vitro study of porcine neonatal islet cells.

PMID- 11959245
TI  - Hydroxymethylated polysulphone for islet macroencapsulation allows rapid
      diffusion of insulin but retains PERV.

PMID- 11959247
TI  - Long-term follow-up of diabetic polyneuropathy after simultaneous pancreas and
      kidney transplantation in type 1 diabetic patients.

PMID- 11959246
TI  - Islet transplantation in seminal vesicles restores glycemia in diabetic rats: a
      preliminary study.

PMID- 11959248
TI  - Simultaneous pancreas-kidney transplant compared with kidney transplant in type I
      diabetic patients with end-stage renal disease.

PMID- 11959249
TI  - HOMA test in diabetic patients with simultaneous pancreas and kidney
      transplantation.

PMID- 11959250
TI  - Clinical noninvasive evaluation of simultaneous pancreas-kidney transplants with
      the combined use of gammagraphy, Doppler ultrasound, and serum markers.

PMID- 11959251
TI  - Combined liver-pancreas transplantation: contribution of five cases.

PMID- 11959252
TI  - High levels of nitric oxide metabolites can be correlated with rejection episodes
      in experimental pancreas transplantation.

PMID- 11959253
TI  - Pancreas transplantation with enteric drainage: duodenal segment leak.

PMID- 11959254
TI  - Children with intestinal failure evaluated for intestinal transplantation in
      Spain.

PMID- 11959255
TI  - Intestinal transplantation: the Spanish experience.

PMID- 11959256
TI  - Origin and immunophenotype of intestinal intraepithelial lymphocytes in
      experimental long-surviving small bowel allografts.

PMID- 11959257
TI  - Liver transplant: marginal donors findings from the Argentine experience.

PMID- 11959258
TI  - Evaluation of potential liver donors: expanding donor criteria?

PMID- 11959259
TI  - Late liver function with graft obtained from donors above 65 years.

PMID- 11959260
TI  - Orthotopic liver transplantation with 100 hepatic allografts from donors over 60
      years old.

PMID- 11959261
TI  - Adult living donor liver transplantation using right lobe.

PMID- 11959262
TI  - Adult living donor liver transplantation: initial results of a starting program.

PMID- 11959263
TI  - Do the results justify living donor and split liver transplant for children in
      Spain?

PMID- 11959264
TI  - Importance of training in liver resection surgery to implement programs of living
      donor liver transplantation.

PMID- 11959265
TI  - Kidney transplants from donors aged over 65 years in comparison with transplants
      from donors aged under 65 years.

PMID- 11959266
TI  - Liver transplants in patients with alcoholic cirrhosis-incidence of acute
      rejection.

PMID- 11959267
TI  - Influence of preoperative factors in liver transplantation for alcoholic
      cirrhosis.

PMID- 11959268
TI  - Liver transplantation in patients with portal thrombosis: results in 76 patients.

PMID- 11959269
TI  - Evaluation of acute renal failure in the liver transplantation perioperative
      period: incidence and impact.

PMID- 11959270
TI  - Influence of donor postreperfusion changes on graft evolution after liver
      transplant.

PMID- 11959272
TI  - Postreperfusion biopsy changes predict biliary complications after liver
      transplantation.

PMID- 11959271
TI  - Prognostic factors of early acute renal failure in liver transplantation.

PMID- 11959273
TI  - Inferior vena cava preservation technique in orthotopic liver transplantation:
      haemodynamic advantages.

PMID- 11959274
TI  - Liver transplantation in the therapy of hepatocellular carcinoma: a revision of
      our series.

PMID- 11959275
TI  - Indications and results of retransplantation after a series of 406 consecutive
      liver transplantations.

PMID- 11959276
TI  - Carcinoid tumour of the common bile duct: an exceptional indication for liver
      transplantation.

PMID- 11959277
TI  - Relationship between cardiovascular state and degree of hepatic dysfunction in
      patients treated with liver transplantation.

PMID- 11959278
TI  - Cystatin C: a marker of glomerular filtration rate in liver transplantation.

PMID- 11959279
TI  - Study of creatinine and creatinine-clearance in liver transplantation.

PMID- 11959280
TI  - Changes in pulmonary circulation during liver transplantation.

PMID- 11959281
TI  - Influence of the basal cardiovascular state on the need for venovenous bypass
      during liver transplantation.

PMID- 11959282
TI  - Effects of norepinephrine on right ventricular function during liver
      transplantation.

PMID- 11959283
TI  - Physiological changes induced by continuous arteriovenous hemodialysis during
      liver transplantation.

PMID- 11959284
TI  - Does mixed venous oxygen saturation reflect the changes in cardiac output during
      liver transplantation?

PMID- 11959285
TI  - Confirmation of graft-versus-host disease by HLA typing after liver
      transplantation.

PMID- 11959286
TI  - Expression of CD95 and apoptosis induction in peripheral blood cells from liver
      graft recipients.

PMID- 11959288
TI  - Causes of mortality after liver transplantation: period of main incidence.

PMID- 11959287
TI  - Predictive factors for postoperatory, early and late mortality in liver
      transplants.

PMID- 11959289
TI  - Recipient factors analysis in long-term allograft survival of liver
      transplantation.

PMID- 11959290
TI  - Incidence and results of arterial complications in liver transplantation:
      experience in a series of 400 transplants.

PMID- 11959291
TI  - Liver function test and prevalence of associated diseases 5 years after liver
      transplantation.

PMID- 11959292
TI  - A two-center, adult/pediatric transplant unit cooperation program for
      cadaveric/living donor liver transplantation and intestinal transplantation.

PMID- 11959293
TI  - De novo tumors after orthotopic liver transplantation.

PMID- 11959295
TI  - Early mortality in liver retransplantation: a multivariate analysis of risk
      factors.

PMID- 11959294
TI  - Outcome of cirrhotic patients with incidental hepatocellular carcinoma undergoing
      liver transplantation.

PMID- 11959296
TI  - Does hepatic retransplantation entail an increase in the number of early
      reoperations? A decade of experience.

PMID- 11959297
TI  - Late liver retransplantation versus early liver retransplantation: indications
      and results.

PMID- 11959298
TI  - Indications for liver retransplantation: 1087 orthotopic liver transplantations
      between 1986 and 1997.

PMID- 11959300
TI  - Sequential (domino) liver transplantation in familial amyloidotic polyneuropathy
      type II.

PMID- 11959299
TI  - Experience with domino or sequential liver transplantation in familial patients
      with amyloid polyneuropathy.

PMID- 11959301
TI  - Reversibility of the neurologic alterations in familial amyloidotic
      polyneuropathy type I after liver transplantation (22 cases).

PMID- 11959303
TI  - Liver transplantation experience in the north of Mexico.

PMID- 11959302
TI  - Simultaneous liver and renal transplantation in a pediatric patient with type I
      hyperoxaluria.

PMID- 11959304
TI  - Influence of cyclosporine on graft regeneration and function after liver
      transplantation: trial in pigs.

PMID- 11959305
TI  - Histology and immunopathology of heart and liver xenografts under low-dose
      tacrolimus.

PMID- 11959306
TI  - Transgenic pig-to-baboon liver xenotransplantation: clinical, biochemical, and
      immunologic pattern of delayed acute vascular rejection.

PMID- 11959308
TI  - Analytical profile comparison between pig and baboon in an orthotopic liver
      xenotransplantation model.

PMID- 11959307
TI  - Assessment of renal function during the postoperative period following liver
      xenotransplantation from transgenic pig to baboon.

PMID- 11959311
TI  - Protocol biopsies and risk factors associated with chronic allograft nephropathy.

PMID- 11959310
TI  - ABO system and blood crossmatch study in baboon: importance of designing a
      primate blood bank for orthotopic pig-to-baboon liver xenotransplantation.

PMID- 11959309
TI  - Acid-base and electrolyte disturbances in an experimental model of orthotopic
      liver xenotransplantation from pig to baboon after graft reperfusion: differences
      between h-DAF livers and unmodified livers.

PMID- 11959312
TI  - Role of smooth muscle cell migration and proliferation in allograft vascular
      disease.

PMID- 11959313
TI  - Treatment of chronic allograft nephropathy with mycophenolate mofetil after
      kidney transplantation: a Spanish multicenter study.

PMID- 11959314
TI  - Prolonged delayed graft function decreases graft survival in transplant patients
      taking cyclosporine.

PMID- 11959315
TI  - Glomerular hyperfiltration, intrarenal hemodynamics, and chronic allograft
      nephropathy: physiopathology of chronic allograft nephropathy.

PMID- 11959316
TI  - Total glomerular number in stable renal allografts.

PMID- 11959318
TI  - Are there differences in renal posttransplant evolution between the first and the
      second recipient from the same donor?

PMID- 11959317
TI  - Renal transplantation with elderly donors: double or single renal
      transplantation?

PMID- 11959319
TI  - Is there any correlation between pathologic changes for acute rejection in kidney
      transplantation (Banff 97) and graft function?

PMID- 11959320
TI  - Renal transplantation in children under 2 years.

PMID- 11959321
TI  - Delayed graft function in kidney transplant recipients: risk factors and short
      term outcome.

PMID- 11959322
TI  - Age as a risk factor in renal transplantation.

PMID- 11959323
TI  - Long-term results of renal transplantation in elderly cadaver donor recipients 65
      years old or older.

PMID- 11959324
TI  - Elderly donor kidney transplantation: arguments for double (dual) versus single
      kidney transplantation.

PMID- 11959325
TI  - Study of nonimmunological factors that could be contributed to development of
      acute vascular rejection.

PMID- 11959326
TI  - Kidney transplantation and pregnancy in a Mexican women sample.

PMID- 11959327
TI  - Study of irregular anti-N antibodies in the hematies of a renal transplant
      patient.

PMID- 11959328
TI  - An early case of de novo membranous nephropathy in a renal transplant patient.

PMID- 11959329
TI  - Persistent proteinuria as a useful parameter to distinguish between chronic renal
      rejection and cyclosporin nephrotoxicity.

PMID- 11959330
TI  - Proteinuria is an independent risk factor of cardiovascular disease in renal
      transplant patient.

PMID- 11959331
TI  - Losartan reduces massive proteinuria in kidney transplant patients: a pilot
      study.

PMID- 11959333
TI  - Apolipoprotein E alleles, dyslipemia and kidney transplantation.

PMID- 11959332
TI  - Lipoprotein(A) in renal transplant recipients.

PMID- 11959334
TI  - Fatty acid composition of low-density lipoprotein in renal transplant recipients
      treated with cyclosporine.

PMID- 11959335
TI  - Oxidation of low-density lipoproteins in renal transplant recipients treated with
      tacrolimus.

PMID- 11959336
TI  - Association between the SstI polymorphism of the apolipoprotein C-III gene,
      glucose intolerance and cardiovascular risk in renal transplant recipients.

PMID- 11959337
TI  - Lipid pattern in kidney-transplanted rats without immunosuppressive therapy.

PMID- 11959338
TI  - Effect of pravastatin treatment on the evolution of extracoronary atherosclerosis
      in renal transplant patients.

PMID- 11959339
TI  - Pravastatin improves low-density lipoprotein oxidation in renal transplantation.

PMID- 11959340
TI  - High-sensitivity C-reactive protein as pretransplant marker for acute rejection
      and cardiovascular morbidity.

PMID- 11959341
TI  - Risk factors of ischemic heart disease after renal transplantation.

PMID- 11959342
TI  - Improvement of mitral dysfunction after kidney transplantation.

PMID- 11959343
TI  - Lipid-lowering long-term effects of six different statins in hypercholesterolemic
      renal transplant patients under cyclosporine immunosuppression.

PMID- 11959344
TI  - Effects of cerivastatin in dyslipemia and other cardiovascular risk factors after
      renal transplantation.

PMID- 11959346
TI  - Bone mass and mineral metabolism in kidney transplant patients.

PMID- 11959347
TI  - Sildenafil (Viagra) in kidney transplant recipients with erectile dysfunction.

PMID- 11959345
TI  - Double-blind, crossover, comparative study of doxazosin and enalapril in the
      treatment of hypertension in renal transplant patients under cyclosporine
      immunosuppression.

PMID- 11959348
TI  - Superior mesenteric venous drainage for kidney transplantation in patients with
      inferior vena cava thrombosis: presentation of two cases.

PMID- 11959349
TI  - Influence of renal posttransplantation dyslipidemia on the degree and severity of
      carotid and femoral atherosclerosis evaluated by B-mode ultrasound.

PMID- 11959350
TI  - Usefulness of a semiquantitative evaluation of Doppler waveforms from kidney
      grafts during dysfunction episodes.

PMID- 11959351
TI  - Exercise capacity in hemodialysis and renal transplant patients.

PMID- 11959358
TI  - Serum cholesterol levels and mood symptoms in the postpartum period.
AB  - During pregnancy, the total serum cholesterol concentration rises up to 43%,
      followed by a rapid fall after delivery. Mild depressive symptoms ('postpartum
      blues') are a common complication of the puerperium and affect 30-85% of women in
      the early postpartum period. Based on these observations, it has been suggested
      that the sudden fall in cholesterol levels after delivery could serve as a
      'natural model' to test the suggested association between cholesterol and mood.
      The present study was designed to expand the database concerning the association
      between cholesterol levels and mood in the postpartum period and to address some
      methodological problems raised by previous studies. Forty-seven healthy
      primiparous women were interviewed with a structured clinical interview on two
      occasions: during late pregnancy (median: day -20 before the expected delivery)
      and during the early postpartum period (median: day 32 after delivery). On both
      occasions, serum concentrations of total and HDL cholesterol were measured and
      mood symptoms were assessed with the state form of Spielberger's State-Trait
      Anxiety Index (STAI), the state form of the State-Trait Anger Scale (STAS), and
      the Beck Depression Inventory (BDI). We found significant, albeit moderate,
      relationships between serum cholesterol levels and mood symptoms in the
      postpartum period that were not present during late pregnancy. Lower postpartum
      levels of total cholesterol were associated with symptoms of anxiety (r=-0.30,
      P=0.04), anger/hostility (r=-0.31, P=0.04), and depression (r=-0.35, P=0.02), and
      lower postpartum levels of HDL cholesterol were associated with symptoms of
      anxiety (r=-0.34, P=0.02). This study confirms that the physiological fall in
      blood lipids in the postpartum period can be a useful model to test the
      relationship between serum cholesterol levels and mood.

PMID- 11959352
TI  - Discrepancies in HLA-C typing in transplantation: comparison of PCR-SSP and
      serology results.

PMID- 11959359
TI  - Relationship of temperament and behaviour measures to the prolactin response to
      fenfluramine in depressed men.
AB  - Low central nervous systems (CNS) serotonin has been linked to aggression,
      impulsivity and disinhibition in both animal and human studies. Low cerebrospinal
      fluid (CSF) 5-hydroxindoleacetic acid (5HIAA) has been reported in violent
      criminals, arsonists and violent suicide attempters. Reduced prolactin response
      to fenfluramine has been found in aggressive patients and criminal offenders.
      Cloninger's dimension of harm avoidance is hypothesised to be related to CNS
      serotonin levels, but studies have reported contradictory results. Forty-eight
      men with major depression received a fenfluramine challenge as well as a number
      of measures of temperament and behaviour: the Tridimensional Personality
      Questionnaire (TPQ); the Eysenck Personality Questionnaire (EPQ); the Barratt
      Impulsivity Scale (BIS); the Hopkins Symptom Checklist (SCL-90); and clinician
      rated personality disorder symptoms. The prolactin response to fenfluramine was
      not related to EPQ or TPQ measures except the TPQ dimension of reward dependence
      and the EPQ Lie scale. The prolactin response to fenfluramine was not related to
      BIS measures or to SCL-90 measures except the SCL-90 somatization scale. The
      prolactin response to fenfluramine was not related to personality disorder
      diagnoses or to a measure of repeated self-harm. Thus, in a sample of moderately
      depressed male outpatients, there was very little relationship between
      personality, behavioural measures and the prolactin response to fenfluramine. We
      suggest that alterations in serotonin functioning, when measured using the
      prolactin response to fenfluramine, may be more commonly linked to behavioural
      abnormalities in personality-disordered or criminal samples.

PMID- 11959360
TI  - Application of the seven-factor model of personality to early childhood.
AB  - The seven-factor model of personality developed by Cloninger and colleagues
      describes personality as a function of developmental aspects of character
      superimposed on heritable dimensions of temperament. The objective of this study
      was to determine whether this model could be applied to early childhood. We
      tested a preschool version of the Temperament and Character Inventory (the
      preschool TCI) in 305 children aged 2-5 years. Exploratory factor analysis
      provided support for the presence of distinct domains of temperament (comprising
      four factors) and character (comprising three factors). The preschool TCI
      demonstrated high internal consistency for each of the seven factors (Cronbach's
      alpha values: 0.70-0.93). Inter-individual differences in novelty seeking, reward
      dependence and cooperativeness were highly preserved (Pearson's r values 0.75,
      0.64 and 0.80, respectively) in 29 subjects who were studied over a 3-year period
      from toddlerhood to early school age. Future studies are warranted to test the
      extent to which early childhood measurements of the seven factors might predict
      the development of personality disorders.

PMID- 11959361
TI  - Temporal association between childhood psychopathology and substance use
      disorders: findings from a sample of adults with opioid or alcohol dependency.
AB  - Adults with substance use disorders (SUD; alcohol or drug abuse or dependence)
      were evaluated to determine if childhood-onset psychopathology preceded the onset
      of SUD. Using structured psychiatric interviews, we assessed 47 clinically
      referred adults with SUD (27 with opioid dependence and 20 with alcohol
      dependence), with attention to childhood-onset psychopathology. A sequence of
      psychopathology and SUD was reconstructed using mean diagnosis onset data. Sixty
      two percent of the 47 SUD adults (mean age 39.3+/-6.6 years) had early-onset SUD
      (defined as < or = 18 years) and 38% had late-onset SUD (> or = 19 years at
      onset). Psychopathology preceded the onset of SUD in 56% of adults. Attention
      deficit/hyperactivity disorder, multiple anxiety, and disruptive disorders
      typically preceded the onset of SUD; in contrast, mood disorders (specifically
      depressive and bipolar disorders) followed the onset of SUD. The majority of
      clinically referred adults with SUD had psychopathology that began in childhood,
      frequently preceding the onset of their SUD. These findings further highlight the
      importance of targeting antecedent disorders for preventive and early
      intervention programs aimed at reducing the risk for SUD.

PMID- 11959362
TI  - Neuropsychological performance in medicated vs. unmedicated patients with
      obsessive-compulsive disorder.
AB  - To date, there have been no formal investigations of neuropsychological
      performance in patients with obsessive-compulsive disorder (OCD) taking
      psychotropic medications. The purpose of this study was to determine whether
      medicated and unmedicated patients with OCD demonstrate differences in
      neuropsychological functioning. Fifty-two patients with a primary DSM-IV
      diagnosis of OCD participated in the study; 28 were taking serotonin reuptake
      inhibitors (SRIs), and 24 were treatment-naive (n=8) or had finished a washout
      period prior to their inclusion in other studies (n=16). The groups were well
      matched with regard to demographic and clinical variables, including symptom
      severity. Each group was administered a comprehensive neuropsychological battery
      to assess general intelligence, attention, verbal and non-verbal working memory,
      declarative and procedural learning, visuo-constructive skills, and executive
      functions. SRI-medicated did not differ from SRI-free patients on any
      neuropsychological measure. Benzodiazepines seemed to improve the patients'
      functioning on a semantic verbal fluency test. In addition, there were
      significant interactions between SRIs and benzodiazepines on the perseverative
      errors of the Wisconsin Card Sorting Test and on reaction times. SRI-medicated
      patients with OCD are able to perform on cognitive functioning tests at a
      comparable level with that of SRI-free patients, and these results have positive
      implications for OCD patients who respond to SRIs. The interactions between SRIs
      and benzodiazepines and their effect on cognition in OCD are likely to be complex
      and deserve further study.

PMID- 11959363
TI  - The Family Questionnaire: development and validation of a new self-report scale
      for assessing expressed emotion.
AB  - The level of expressed emotion (EE) as assessed in the Camberwell Family
      Interview (CFI) has proved to be one of the best predictors of relapse in
      schizophrenia. The present study describes the development and validation of the
      Family Questionnaire (FQ), a brief self-report questionnaire measuring the EE
      status (criticism, emotional overinvolvement) of relatives of patients with
      schizophrenia. The FQ classifications in the initial sample of relatives (N=76)
      correlated significantly with the ratings in the CFI subcategories 'criticism'
      (78% correct classifications) and 'emotional overinvolvement' (71% correct
      classifications), as well as with the overall CFI EE ratings (74% correct
      classifications). A validation study in an independent second sample (N=79)
      yielded similar results. The overall correct classification rate of 74% remained
      unchanged. The FQ had better agreement with the CFI on emotional overinvolvement
      than did other short EE questionnaires.

PMID- 11959364
TI  - Functional brain asymmetry and attentional modulation in young and stabilised
      schizophrenic patients: a dichotic listening study.
AB  - Impaired functional brain asymmetry has been shown in schizophrenic patients, in
      addition to attentional deficits related to this laterality impairment. However,
      it has usually been shown in older patients with frequent positive symptoms. This
      is a matter of concern because previous studies have suggested that such deficits
      interact with subgroup characteristics, especially positive symptoms like
      hallucinations and age/duration of the illness. Thus, in this study, we tested a
      homogeneous group of young and stabilised schizophrenic patients. We used a
      verbal dichotic listening test with consonant-vowel syllables to study brain
      asymmetry and attentional modulation. Nineteen patients were compared with
      healthy subjects with the same age, handedness and gender distribution. All
      subjects were tested during a divided and two focused attention conditions. The
      patient and reference group showed the same performance pattern. This indicates
      that young and stabilised patients show normal functional brain asymmetry and
      normal ability to modulate attention. It is suggested that impairments in
      functional asymmetry and attentional modulation may follow a continuum related to
      symptomatology and age/duration of illness.

PMID- 11959365
TI  - Use and automation of a rule in schizophrenia.
AB  - Schizophrenia is associated with cognitive deficits and information-processing
      anomalies. Several studies have shown impairments in frontal lobe functions such
      as discovering rules, adopting strategies and working memory. We have evaluated
      the performances of schizophrenic patients on three different tasks of
      information processing. The first was a simple reaction time task, the second
      consisted of discriminating the color of the stimuli, and the third required the
      use of a rule of permutation. The schizophrenic patients (n=17) showed a task
      dependent increase in time for responses in comparison with the control group
      (n=17). This increase was particularly important in the last task, which requires
      the use of the rule. These results confirm and expand the previously described
      impairment of patients with schizophrenia in the ability to use rules. They are
      discussed in terms of deficit in executive functions probably due to frontal lobe
      malfunctioning.

PMID- 11959366
TI  - Risperidone-induced increase in serum prolactin is correlated with positive
      symptom improvement in chronic schizophrenia.
AB  - The elevation in serum prolactin (PRL) concentration in schizophrenic patients
      treated with typical antipsychotic drugs is well documented. Recently, increased
      prolactin levels have been reported in patients taking risperidone. The purpose
      of this study was to explore the effect of the atypical antipsychotic drug
      risperidone on serum prolactin, and to investigate the relationship between the
      change in PRL and the therapeutic outcome. In this study, 30 male inpatients with
      a diagnosis of chronic schizophrenia (DSM-III-R) were assigned to 12 weeks of
      treatment with risperidone after a 2-week washout period. The risperidone dose
      was fixed at 6 mg/day. Clinical efficacy was determined using the Positive and
      Negative Syndrome Scale (PANSS). Serum PRL was assayed in serum by
      radioimmunometric assay in schizophrenic patients before and after 12-week
      treatment, as compared to 30 age-matched normal male subjects. The results showed
      that risperidone treatment significantly increased the serum PRL. A significant
      and positive relationship between the change in PRL at pre- and post-treatment
      and the reduction rate of PANSS positive subscore was observed. Risperidone
      treatment significantly increased the serum PRL levels of schizophrenic patients.
      There was a close relationship between the improvement in positive symptoms and
      the change of serum PRL level before and after risperidone treatment. The serum
      PRL levels at baseline could be used to predict the responses of schizophrenic
      patients to risperidone.

PMID- 11959367
TI  - Procedural memory in schizophrenia assessed using a mirror reading task.
AB  - The preservation of procedural memory in individuals with schizophrenia has been
      confirmed by methods such as the Tower of Hanoi, pursuit rotor and mirror reading
      tests. However, the cognitive procedural memory of Japanese subjects with
      schizophrenia has never been assessed using mirror reading. To better determine
      the characteristics of cognitive procedural memory in schizophrenia, a Japanese
      version of the mirror reading task, consisting of cards with words written in
      Japanese katakana characters in mirror image, was administered to 18 Japanese
      patients with schizophrenia and 21 normal controls. The results indicated that
      the patients indeed learned the skill despite exhibiting lower overall
      performances in reading time than the controls, their scores displaying
      correlation with the severity of schizophrenic negative symptoms. This suggests
      that procedural memory for this task is retained in individuals with
      schizophrenia. It is important for them to use their preserved procedural memory
      for efficient rehabilitative efforts.

PMID- 11959368
TI  - Expression of pituitary adenylate cyclase-activating polypeptide and PACAP type 1
      receptor in the rat gastric and colonic myenteric neurons.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to regulate
      gastric acid secretion and intestinal motility. In the present study, the pattern
      of distribution of PACAP and PACAP type 1 receptor (PAC1) immunoreactivities were
      examined in the rat stomach and distal colon using a specific polyclonal antibody
      raised against rat/human PAC1. Western blot of the membrane preparations of
      NIH/3T3 cells transfected with the human PAC1 obtained by using rabbit polyclonal
      anti-PAC1 antibody showed a protein band with a molecular mass of approximately
      50 kDa. NIH/3T3 cells transfected with the human PAC1 and incubated with the anti
      PAC1 antibody displayed surface cell-type immunoreactivity, which was
      internalized following ligand exposure. In gastric or colonic longitudinal
      muscle/myenteric plexus (LMMP) whole mount preparations as well as cryostat
      sections, PACAP immunoreactivity was observed in cell bodies within the myenteric
      ganglia and nerve fibers in the muscle layers and mucosa. PAC1 immunoreactivity
      was confined mainly on the surface of the nerve cells. PACAP and PAC1
      immunoreactivities showed a similar pattern of distribution in gastric and
      colonic tissues. Adjacent sections or LMMP whole mount preparations labeled with
      protein gene product 9.5 (PGP 9.5) revealed the neuronal identity of myenteric
      cells bearing PAC1. The neuronal localization of PACAP and PAC1 receptors
      supports their role in the neural regulation of gastric acid secretion and
      gastrointestinal motor function.

PMID- 11959369
TI  - Involvement of nitric oxide and potassium channels in the bradykinin-induced
      vasodilatation in the rat kidney perfused ex situ.
AB  - The role of nitric oxide (NO), K(+) channels, and arachidonic acid metabolism,
      via cytochrome P450 and cyclooxygenase pathways, in the renal vasodilatory effect
      of bradykinin was examined in the isolated rat kidney perfused ex situ with a
      blood-free solution. Bradykinin (BK, 0.25-1.0 microM) induced a dose-dependent
      reduction of 10-35% in the relative renal vascular resistance (rRVR) of isolated
      kidneys preconstricted with phenylephrine (PHE, 0.17-0.35 microM). The
      vasodilating effect of 0.5 microM bradykinin was significantly inhibited by the
      nitric oxide synthase inhibitors, N(G)-nitro-L-arginine (95% inhibition) and N(G)
      nitro-L-arginine methyl ester (45-75% inhibition). Clotrimazole, an inhibitor of
      cytochrome P450 pathway but not indomethacin, a cyclooxygenase inhibitor, reduced
      the renal vasodilator response to bradykinin by 84%. The nonspecific K(+) channel
      inhibitor, tetraethylammonium ion (TEA) and the selective inhibitor of Ca(2+)
      activated K(+) channels, charybdotoxin (ChTX) greatly attenuated the vasodilator
      response to bradykinin by approximately 84% and 79%, respectively. These two K(+)
      channel inhibitors showed similar effects on vasodilatation induced by S-nitroso
      acetyl-D,L-penicillamine (1 microM), a nitric oxide donor. The results suggest
      that bradykinin releases nitric oxide which, by opening potassium channels
      specifically the Ca(+)-dependent type, mediates the renal vasodilator response to
      bradykinin in the isolated kidney perfused ex situ.

PMID- 11959370
TI  - Diabetes-induced changes of nitric oxide influence on the cardiovascular action
      of secretin.
AB  - The modulation by condition of the lack or the excess of nitric oxide (NO) on
      cardiovascular action of secretin in diabetic rats was investigated. In vitro the
      isolated heart function and in vivo, the systolic (SBP), diastolic (DSP) blood
      pressure and heart rate (HR) were measured. Secretin evoked inotropic positive
      effect and increased coronary outflow (CO), in vivo did not increase systemic
      pressure and the highest dose of the peptide increased the heart rate. NO
      synthase inhibitor, N(G) nitro-L-arginine methyl ester (L-NAME) deeply increased
      the systemic pressure and in vitro decreased coronary outflow. L-arginine and
      sodium nitroprusside (SNP) did not influence the isolated heart function and in
      vivo decreased the systemic pressure. L-NAME preserved the inotropic positive
      effect of secretin and the increase of the coronary outflow. In vivo co
      administration of L-NAME+secretin evoked hypotensive effect and abolished the
      increase of the heart rate after the highest dose of the peptide. L-arginine
      abolished inotropic positive effect of the peptide and the increase of coronary
      outflow. In vivo co-administration of these substances caused hypotension and
      attenuated the increase of the heart rate after the highest dose of secretin. Co
      injection of SNP and secretin preserved the inotropic effect of secretin and
      abolished the increase of the coronary outflow. In vivo infusion of SNP+secretin
      evoked hypotension and similarly to L-arginine, SNP abolished tachycardia induced
      by the highest dose of secretin. Both the lack and the excess of nitric oxide
      changed the cardiovascular action of secretin in diabetic rats.

PMID- 11959371
TI  - Immunoneutralization of endogenous glucagon-like peptide-2 reduces adaptive
      intestinal growth in diabetic rats.
AB  - Supraphysiological doses of glucagon-like peptide-2 (GLP-2) have been shown to
      induce intestinal growth by increasing villus height and crypt depth and by
      decreasing apoptosis, but a physiological effect of GLP-2 has not yet been
      demonstrated. Earlier, we found elevated levels of endogenous GLP-2 in untreated
      streptozotocin diabetic rats associated with marked intestinal growth. In the
      present study, we investigated the role of endogenous GLP-2 for this adaptive
      response. We included four groups of six rats: (1) diabetic rats treated with
      saline, (2) diabetic rats treated with non-specific antibodies, (3) diabetic rats
      treated with polyclonal GLP-2 antibodies and (4) non-diabetic control rats
      treated with saline. All animals were treated with once daily intraperitoneal
      injections for 13 days and killed on day 14. Diabetic rats treated with saline or
      non-specific antibodies had a significantly (P<0.01) increased area of mucosa
      (13.00+/-0.64 and 13.37+/-0.60 mm(2), respectively) in the proximal part of the
      small intestine compared with non-diabetic controls (7.97+/-0.70 mm(2)). In
      contrast, diabetic rats treated with GLP-2 antibodies had a significantly
      (P<0.01) smaller increase in area of mucosa in the proximal part of the small
      intestine (10.84+/-0.44 mm(2)). Antibody treatment had no effect on body weight,
      blood glucose concentrations and food intake. Thus, blocking of endogenous GLP-2
      in a model of adaptive intestinal growth reduces the growth response, providing
      strong evidence for a physiological growth factor function of GLP-2.

PMID- 11959372
TI  - Attenuation of negatively regulated ANP secretion by calcium in hypertrophied
      atria.
AB  - Abnormal intracellular Ca(2+)-handling has been described in various heart
      diseases associated with cardiac hypertrophy. The crucial role of Ca(2+) in the
      excitation-secretion coupling in atrial cardiomyocytes is not well established.
      To investigate modulation of atrial natriuretic peptide (ANP) secretion regulated
      by Ca(2+) in hypertrophied atria, responsiveness of stretch-induced ANP to Ca(2+)
      was studied using isolated perfused quiescent hypertrophied rat atria. Male
      Sprague-Dawley rats were given a single subcutaneous injection of 50 mg/kg
      monocrotaline (MCT) and were sacrificed at 5-6 weeks. In isolated perfused
      hypertrophied right atria from MCT rats, changes in atrial volume induced by
      increased atrial pressure caused proportional increases in mechanically
      stimulated extracellular fluid (ECF) translocation and stretch-induced ANP
      secretion. Stretch-induced ANP secretion was markedly increased by the depletion
      of extracellular Ca(2+). However, an accentuation of stretch-induced ANP
      secretion by Ca(2+) depletion was markedly attenuated in hypertrophied right
      atria, as compared to control right atria. Therefore, stretch-induced ANP
      secretion in terms of ECF translocation by Ca(2+) depletion in hypertrophied
      atria was significantly lower than in control right atria. However, no
      significant differences were observed between nonhypertrophied and control left
      atria. Depletion of extracellular Ca(2+) caused a decrease in intracellular
      calcium in single beating atrial myocytes, which was significantly attenuated in
      hypertrophied atrial myocytes. The results suggest that attenuation of Ca(2+)
      induced negative regulation of ANP secretion in hypertrophied atria may be due to
      the disturbance of intracellular Ca(2+) regulation.

PMID- 11959374
TI  - Increased somatostatin mRNA expression in periventricular nucleus of rat
      hypothalamus during hypoxia.
AB  - We reported that hypoxia inhibited the growth hormone (GH) and induced
      somatostatin (SS) release from the hypothalamic median eminence (ME) of rats.
      This study is designed to examine the SS mRNA alterations in the periventricular
      nucleus (PeN) of the hypothalamus in rats and the possible involvement of
      glucocorticoid (GC) during hypoxia. Rats were exposed to hypoxia in a simulated
      hypobaric chamber. SS mRNA levels in the PeN were tested by in situ
      hybridization. Hypoxia of 5-km altitude (10.8% O(2)) for 2, 5 and 24 h increased
      the SS mRNA expression by 34.72%, 50.31% and 95.05% (p<0.05), respectively.
      Severe hypoxia of 7-km altitude (8.2% O(2)) enhanced the SS expression by 79.08%
      (p<0.01), 74.90% (p<0.01) and 71.40% (p<0.05), respectively. Prolonged hypoxia (5
      km for 5 days) exposure augmented a 2.5-fold SS mRNA (p<0.001). One week post
      adrenalectomy (ADX), SS mRNA level was significantly increased. During hypoxia, 5
      km for 5 h, SS mRNA in ADX rats was not further increased. An increased SS mRNA
      was showed by pretreatment with low dose of dexamethasone (DEX) (125 microg/kg,
      i.p.) to ADX animals but this increase was depressed by a high dose of DEX (500
      microg/kg, i.p.). The data suggested that (1) hypoxia stimulated the expression
      of SS mRNA in the PeN of rat hypothalamus. (2) Increased circulating GC levels
      might play a role in upregulating the SS mRNA in the rat PeN during hypoxia.

PMID- 11959373
TI  - Two classes of endothelin receptors mediating contraction in esophageal
      muscularis mucosae.
AB  - Endothelin (ET) causes contraction of the esophageal muscularis mucosae. To
      characterize the ET receptor subtypes involved in contraction, we measured
      contraction of isolated muscularis mucosae strips caused by ET-related peptides
      and binding of (125)I-ET-1 to cell membranes prepared from the guinea pig
      esophageal muscularis mucosae. Autoradiography demonstrated (125)I-ET-1 binding
      to the muscularis mucosae and muscularis propria. ET-1 caused tetrodotoxin and
      atropine-insensitive contraction of esophageal muscularis mucosae strips. The
      relative potencies for ET isopeptides to cause contraction were ET-1=ET-2>ET-3.
      FR-139317, an ET(A) receptor antagonist, or BQ-788, an ET(B) receptor antagonist,
      alone did not alter responses to ET-1. However, the combination of both
      antagonists almost abolished the ET-1-induced contraction, indicating synergistic
      inhibition. Desensitization to sarafotoxin S6c, an ET(B) receptor agonist, failed
      to abolish the response to ET-1, which was completely inhibited by FR-139317.
      These indicate the involvement of both ET(A) and ET(B) receptors in the
      contraction. Binding of (125)I-ET-1 to cell membranes of the muscularis mucosae
      was saturable and specific. Analysis of dose-inhibition curves demonstrated the
      presence of ET(A) and ET(B) receptors. This study demonstrates that the
      esophageal muscularis mucosae possesses both ET(A) and ET(B) receptors mediating
      muscle contraction. There is cooperation between these two subtypes of ET
      receptors in the esophagus mediating muscle contraction.

PMID- 11959375
TI  - Differential glucocorticoid effects on repair mechanisms and NF-kappaB activity
      in the intestinal epithelium.
AB  - Glucocorticoids are effective agents in the management of inflammatory bowel
      diseases. However, information about their effects on repair mechanisms of the
      intestinal epithelium is incomplete.Therefore, the aim was to analyse in vitro
      effects of glucocorticoids on proliferation, restitution, and apoptosis as well
      as their effects on activity and expression of nuclear factor (NF)-kappaB, a
      known regulator of apoptosis and inflammation, in intestinal epithelial cells.Non
      transformed rat jejunum epithelial cells (IEC-6) were cultured in the presence
      and absence of various concentrations of prednisolone and budesonide. IEC-6 cell
      proliferation was assessed by [3H]-thymidine incorporation. Restitution was
      analysed by an IEC-6 in vitro assay. Apoptosis was evaluated by ELISA and
      fluorescence microscopy. DNA binding activity and nuclear expression of NF-kappaB
      was determined by electrophoretic mobility shift assays and Western blotting,
      respectively. Prednisolone and budesonide stimulated IEC-6 cell proliferation at
      low to medium pharmacologic concentrations (prednisolone: 10(-9) to 10(-6) M;
      budesonide: 10(-11) to 10(-8) M). In contrast, high concentrations (>5 x 10(-5)
      M) had inhibitory effects on proliferation. 10(-7) M prednisolone and 10(-8) M
      budesonide increased restitution of IEC-6 cells, whereas high concentrations (10(
      4) M) of prednisolone and budesonide decreased restitution. Apoptosis of IEC-6
      cells was substantially enhanced by 10(-4) M budesonide; apoptosis was slightly
      increased by the highest prednisolone concentration used (5 x 10(-4) M).
      Furthermore, both glucocorticoids inhibited DNA binding activity and nuclear NF
      kappaB expression in IEC-6 cells in a dose- and time-dependent fashion. In
      conclusion, prednisolone and budesonide modulate repair mechanisms of intestinal
      epithelial cells in vitro in a dose-dependent manner and profoundly modulate the
      inflammatory regulator NF-kappaB.

PMID- 11959377
TI  - Left ventricular mass, arterial compliance and high risk of coronary heart
      disease in South Asians.

PMID- 11959376
TI  - Left ventricular mass and arterial compliance: relation to coronary heart disease
      and its risk factors in South Indian adults.
AB  - BACKGROUND: Rates of coronary heart disease (CHD) in India are rising, and are
      now similar to those in Western countries. The prevalence of conventional CHD
      risk factors such as hypercholesterolaemia, hypertension, smoking and obesity,
      tend to be lower in Indian than Western populations, and fail to explain these
      high rates of disease. Increased left ventricular (LV) mass and decreased
      arterial compliance predict a higher risk of CHD in Western populations, but
      there are no published data from India. We have measured LV mass and arterial
      compliance, and examined their relation to CHD and other known risk factors, in
      men and women living in Mysore, South India. METHODS: We examined 435 men and
      women born in Mysore during 1934-1953. LV mass was measured by echocardiography
      and arterial compliance (derived from pulse wave velocity, PWV) was measured by a
      non-invasive optical method in three arterial segments. RESULTS: The mean LV mass
      was 149 g (S.D. 37) in men and 125 g (S.D. 32) in women. The mean PWV was 4.14
      m/s in the aorto-radial, 3.28 m/s in the aorto-femoral and 13.59 m/s in the
      femoro-popliteal-posterior tibial segments. LV mass and PWV were positively
      correlated with each other and with systolic and diastolic blood pressures, non
      insulin dependant diabetes mellitus, fasting plasma glucose, insulin, proinsulin
      concentrations and serum triglyceride concentrations (p<0.05 for all),
      independently of age, sex and body size. In addition, LV mass correlated
      negatively with fasting serum HDL-cholesterol (p=0.02). Higher LV mass was
      associated with an increased risk of CHD (p=0.05). CONCLUSIONS: The mean LV mass
      in this Indian population is low compared with Western populations, though as in
      the West, increased LV mass is associated with an increased risk of CHD. Greater
      LV mass and reduced arterial compliance are associated with higher levels of many
      known CHD risk factors especially with those which form the Insulin Resistance
      Syndrome.

PMID- 11959378
TI  - Plasma profiles of peripheral monocyte-related inflammatory markers in patients
      with arterial hypertension. Correlations with plasma endothelin-1.
AB  - BACKGROUND: This study investigates the plasma activity of inflammatory mediators
      such as granulocyte-macrophage colony-stimulating factor (GM-CSF), C-C chemokines
      and soluble adhesion molecules, produced by monocyte-endothelial cell adhesive
      interaction, in patients with arterial hypertension. METHODS: We studied 66
      untreated patients with mild to moderate arterial hypertension
      (hypercholesterolemic: 34, normocholesterolemic: 32) and 30 sex- and age-matched
      normocholesterolemic normotensive controls. Plasma concentrations of GM-CSF,
      macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein
      1alpha (MIP-1alpha), RANTES (regulated on activation normally T-cell expressed
      and secreted), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble
      vascular cell adhesion molecule-1 (sVCAM-1), as well as plasma endothelin-1 (ET
      1), were determined in study population by ELISA and RIA, respectively. RESULTS:
      Hypertensives exhibited significantly higher levels of GM-CSF (6.5+/-1.3 vs.
      2.3+/-0.7 pg/ml, P=0.099), MCP-1 (175+/-31 vs. 120+/-24 pg/ml, P=0.0093), MIP
      1alpha (23+/-4 vs. 15+/-2 pg/ml, P=0.0089), RANTES (17+/-4 vs. 14+/-3 ng/ml,
      P=0.047), sICAM-1 (235+/-39 vs. 187+/-21 ng/ml, P=0.0041), sVCAM-1 (684+/-42 vs.
      589+/-23 ng/ml, P=0.0045) and ET-1 (6.1+/-1.5 vs. 2.4+/-0.3 pg/ml, P=0.0095) than
      those of normotensives. The normocholesterolemic hypertensives had significantly
      lower levels of GM-CSF, MCP-1, MIP-1alpha, sICAM-1 and sVCAM-1 than
      hypercholesterolemic hypertensives but higher than normotensives. In
      hypertensives, ET-1 levels were significantly correlated with mean arterial
      pressure (r=0.51, P=0.028), MCP-1 values (r=0.45, P=0.047) and sICAM-1 levels
      (r=0.64, P=0.0090). Significant correlations were also found between LDL
      cholesterol values and plasma inflammatory factors GM-CSF (r=0.58, P=0.0088), MCP
      1 (r=0.49, P=0.040) and sICAM-1 (r=0.53, P=0.034) in the hypercholesterolemic sub
      group of hypertensives. CONCLUSIONS: Inflammatory markers of monocyte-endothelial
      cell adhesive interaction are elevated in hypertensives in comparison to
      normotensives and may be related to plasma ET-1 activity. The coexistence of
      hypercholesterolemia may enhance this inflammatory process induced by arterial
      hypertension.

PMID- 11959379
TI  - Chemokines and other novel inflammatory markers in hypertension: what can their
      plasma levels tell us?

PMID- 11959380
TI  - Effect of exercise training on skeletal muscle fibre characteristics in men with
      chronic heart failure. Correlation between skeletal muscle alterations, cytokines
      and exercise capacity.
AB  - BACKGROUND: In patients with congestive heart failure (CHF) there is a shift from
      aerobic type I muscle fibres to less aerobic type II fibres. Exercise training
      has been shown to have beneficial effects on exercise performance, peripheral
      pathology and the neurohumoral profile in stable patients with CHF. This study
      evaluated the effect of a 3 month exercise training program on skeletal muscle
      characteristics and the correlation of these to cytokines and exercise capacity
      in CHF patients. METHODS: Skeletal muscle biopsies for enzyme-histochemical
      analysis were performed in 15 CHF patients in New York Heart Association classes
      II-III, with a mean ejection fraction of 33+/-5% before and after a 12 week
      training period. The patients were trained for 30 min, five times a week at 80%
      of the peak heart rate achieved at baseline ergometer cycle test. Fifteen healthy
      men were used as controls. Plasma samples were examined by enzyme immunoassays
      for levels of pro-inflammatory cytokines. RESULTS: (a) At baseline we found
      muscle atrophy in five of the patients. The percent area of type I fibres (40.7+/
      12.0 vs. 56.4+/-11.0%, P<0.05) and the thickness of type IIA (56.10+/-7.8 vs.
      71.6+/-11.9 microm, P<0.001) and B-fibres (49.0+/-8.9 vs. 63.9+/-10.6 microm,
      P<0.001) were reduced, whereas the percent area of type IIA fibres (52.1+/-13.3
      vs. 36.4+/-9.9%, P<0.05) was increased in heart failure patients compared to
      healthy controls. There was a modest correlation between fibre thickness and the
      level of interleukin 6 (r=-0.657, P=0.008). (b) After exercise training there was
      a reduction in muscle area examined by light-microscopy, measured as a percentage
      of field (-2.7, P=0.003) with an concomitant increase in interstitium. This
      reduction correlated to the increase in the 6-min walk test (r=-0.558, P=0.031).
      The thickness of type IIB fibres increased (+5.6 microm, P=0.068) and the area of
      type I fibres decreased (-6.1%, P=0.062). CONCLUSIONS: Patients with CHF have a
      relatively increased area of type IIA fibres and a relatively decreased area of
      type I fibres compared to healthy individuals. The thickness of type IIA and type
      IIB fibres is decreased compared to normal individuals. A modest negative
      correlation between the level of interleukin 6 and fibre thickness at baseline,
      suggests that inflammatory cytokines may be involved in the pathogenesis of the
      CHF related myopathy. A significant correlation between the reduction of muscle
      area, with increased interstitum, and the increase in the 6-min walk test may
      indicate that the improvement is due to increased capillary density permitting
      better flow reserve to exercising muscles.

PMID- 11959381
TI  - Skeletal muscle response to exercise and treatment: another sibyl in the heart
      failure syndrome?

PMID- 11959382
TI  - Prognostication and risk stratification by assessment of left atrioventricular
      plane displacement in patients with myocardial infarction.
AB  - BACKGROUND: Mean left atrioventricular plane displacement is strongly related to
      prognosis in patients with heart failure. We aimed to examine its value for
      prognostication and risk stratification in patients hospitalised for acute
      myocardial infarction. METHODS AND RESULTS: Left atrioventricular plane
      displacement was assessed by echocardiography in 271 consecutive patients with
      acute myocardial infarction. Mean prospective follow-up was 628 days.
      Atrioventricular plane displacement was readily assessed in all patients and was
      significantly lower in patients who died (n=41, 15.1%) compared to the survivors:
      8.2(5.6) v. 10.0(5.5) mm, P<0.0001. Overall mortality was 31.3% in the lowest
      quartile with regard to atrioventricular plane displacement (<8.00 mm) and 10.1%
      in the combined upper three quartiles. Thus, the hazard ratio for an
      atrioventricular plane displacement <8.0 mm compared to 8 mm or more was 3.1,
      P=0.0001. The combined mortality/heart failure hospitalisation incidence was
      43.8% in the lowest and 14.6% in the combined upper three quartiles: Risk ratio
      3.0, P<0.0001. In multivariate analysis, including age and history of atrial
      fibrillation, left atrioventricular plane displacement was an independent
      prognostic marker. CONCLUSION: In post-myocardial infarction patients,
      echocardiographic assessment of atrioventricular plane displacement showed a
      strong, independent prognostic value. Determination of left atrioventricular
      plane displacement can be readily performed in virtually all patients, and may in
      clinical practice facilitate identification of high-risk patients.

PMID- 11959383
TI  - Plasma fibrinogen and troponin I in acute coronary syndrome and stable angina.
AB  - We aimed to determine whether there is a stratification among patients with
      different stages of coronary artery disease with respect to plasma fibrinogen
      levels, and to assess diagnostic value of plasma fibrinogen in comparison to
      troponin I in patients with acute coronary syndrome. Fifty-one consecutive
      patients presenting to our department with acute coronary syndrome within the
      last 24 h and 52 patients with stable angina with no episode of unstable disease
      within the last month were analysed. Forty-nine patients with acute coronary
      syndrome in which both troponin I and fibrinogen levels were present were further
      evaluated. Blood was collected on admission for routine laboratory tests.
      Statistical analysis was done using Student's t-test, Pearson correlation and chi
      square test, P<0.05 being considered statistically significant. Plasma fibrinogen
      levels (g/l) were significantly higher in patients presenting with unstable than
      with stable angina (3.87+/-1.2 vs. 3.26+/-0.65 P=0.002). We have found
      significant correlation between fibrinogen and troponin I levels in unstable
      patients (r=0.43, P=0.0015). In patients with acute coronary syndrome an
      increased inflammation and cardiac injury seem to coexist and correlate. These
      results seem to confirm the role of this acute phase protein in the
      pathophysiology of acute coronary syndrome.

PMID- 11959384
TI  - Absence of change of signal-averaged electrocardiogram identifies patients with
      ventricular arrhythmias who are non-responders to amiodarone.
AB  - OBJECTIVES: The aim of this study was to assess the ability of a non-invasive
      study, the signal-averaged ECG (SAECG), to predict the effect of amiodarone at
      ventricular level. BACKGROUND: Amiodarone is the main drug drug used in the
      treatment of ventricular arrhythmias. Standard ECG does not detect any change in
      QRS complex resulting from amiodarone therapy. SAECG is more sensitive than ECG
      for detecting changes in QRS complex. METHODS: The study examined the effects of
      amiodarone on SAECG in relation to the results of programmed ventricular
      stimulation in 68 patients with old myocardial infarction, spontaneous and
      inducible sustained ventricular tachycardia (VT). RESULTS: Amiodarone prolonged
      the total QRS duration (dur) (129+/-28 vs. 140+/-30 ms, P<0.05) and low amplitude
      signal (LAS) dur (45+/-20 vs. 51+/-20 ms, P<0.1), whereas the root-mean-square
      voltage of the last 40 ms of QRS complex (RMS 40) was significantly reduced (20+/
      16 vs. 14+/-9 microV, P<0.05). Changes in SAECG parameters did not differ
      significantly in patients in whom amiodarone prevented the inducibility of VT
      (n=15) and those in whom VT remained inducible with amiodarone (n=53), but in
      baseline QRS duration was significantly shorter in patients in whom amiodarone
      prevented the VT induction (118+/-26 vs. 133+/-28 ms, P<0.05). In patients in
      whom amiodarone did not prolong the cycle length of VT (n=15), SAECG did not
      change significantly (QRS dur 131+/-29 vs. 132+/-27 ms, LAS 42+/-20 vs. 42+/-19
      ms, RMS 40 22+/-14 vs. 19+/-11 microV). Comparison of the SAECG data in patients
      with no inducible VT and those with slowed VT differed significantly (P<0.05)
      between the control state and the recording with amiodarone. CONCLUSIONS: The
      effects of amiodarone on VT inducibility are predicted by a shorter baseline QRS
      duration and the degree of drug-induced prolongation of filtered QRS duration.
      Amiodarone prolonged the QRS duration, LAS duration and decreased RMS 40; this
      effect was more important in patients with no inducible VT and in those with only
      slowed VT, than in patients with unchanged or accelerated VT. The absence of
      changes of QRS duration predicted the induction of a more rapid or not slowed VT
      with amiodarone with a sensitivity of 87% and a specificity of 83%. Therefore,
      SAECG appears as an useful and simple means to predict the effects of amiodarone
      in patients with myocardial infarction and VT.

PMID- 11959385
TI  - Hemodynamic basis of the reduced oxygen uptake relative to work rate during
      incremental exercise in patients with chronic heart failure.
AB  - BACKGROUND: The ratio of the increase in oxygen uptake to the increase in work
      rate (DeltaVO2/DeltaWR) during incremental exercise is reduced in patients with
      severe chronic heart failure (CHF). However, the pathophysiological basis of the
      reduced O2 uptake relative to work rate has not been elucidated. METHODS: To
      elucidate the hemodynamic basis of the reduced ratio of DeltaVO2/DeltaWR during
      exercise in severe CHF, 48 patients with CHF (15 patients in class I, 21 in class
      II and 12 in class III) performed maximal ergometer exercise with respiratory gas
      analysis. Cardiac output and systemic O2 extraction were measured at 1-min
      intervals during exercise. RESULTS: Both peak VO2 and peak cardiac output
      decreased as the severity of CHF advanced. Patients in class III showed
      significantly reduced DeltaVO2/DeltaWR than those in class I (8.2+/-0.9 vs. 9.8+/
      1.5 ml/min/W, P<0.01). Cardiac output at rest was significantly lower, and O2
      extraction at rest was significantly higher in class III than class I. The ratio
      of the increase in cardiac output to the increase in work rate (DeltaCO/DeltaWR)
      was significantly lower in class III than class I (42.5+/-14.5 vs. 60.6+/-10.3
      ml/min/W), and the ratio of the increase in O2 extraction to the increase in work
      rate (DeltaO2 extraction/DeltaWR) was significantly higher in class III than
      class I (0.45+/-0.13 vs. 0.34+/-0.08%/W). The DeltaVO2/DeltaWR was significantly
      correlated with the DeltaCO/DeltaWR (r=0.67, P<0.01), and the DeltaCO/DeltaWR was
      inversely correlated with DeltaO2 extraction/DeltaWR (r=-0.65, P<0.01).
      CONCLUSIONS: Decreased O2 supply due to reduced cardiac output was not fully
      compensated by the increased O2 extraction. Reduced ratio of DeltaVO2/DeltaWR in
      advanced CHF reflected the severely attenuated cardiac output response to
      exercise.

PMID- 11959386
TI  - Different associations of C-reactive protein, fibrinogen and C3 with traditional
      risk factors in middle-aged men.
AB  - BACKGROUND: Some acute phase proteins are associated with both ischemic events
      and traditional risk factors. Since they are strongly interrelated, each of them
      partly reflects the characteristics of other proteins. This study was carried out
      to ascertain the specific preferential associations of some acute phase proteins
      with traditional risk factors for atherosclerotic disease. METHODS: High
      sensitivity C-reactive protein, fibrinogen and C3-complement were assessed in 288
      unselected men aged 55-64 years. Three multiple linear regression analyses were
      performed, in which each of the three acute phase proteins was considered the
      dependent variable of both traditional risk factors and the other two proteins.
      RESULTS: The three acute phase proteins strongly correlated with each other.
      Moreover, C-reactive protein was independently associated with triglycerides
      (P<0.0001), age (P=0.0130), body mass index (P=0.0179), and acute (P=0.0280) and
      chronic (P=0.0582) inflammations (R2=0.17). Fibrinogen was associated with
      alcohol consumption (inversely, P=0.0001) and smoking (P=0.0598) (R2=0.06).
      Finally, C3 was associated with insulin (P<0.0001), cholesterol (P=0.0001),
      sedentarity (P=0.0028), glucose (P=0.0077), and systolic blood pressure
      (P=0.0124) (R2=0.28). CONCLUSIONS: When simultaneously studied in multivariate
      analysis, acute phase proteins have different preferential associations with
      traditional risk factors, a probable consequence of their involvement in
      different cellular activations and metabolic processes.

PMID- 11959387
TI  - Insulin resistance in moderate chronic heart failure is related to
      hyperleptinaemia, but not to norepinephrine or TNF-alpha.
AB  - OBJECTIVES: Chronic heart failure (CHF) has emerged as an insulin-resistant
      state, independently of ischaemic aetiology. The underlying mechanisms of this
      finding are not known. Catecholamines, tumor necrosis factor alpha (TNFalpha) and
      leptin, the adipocyte specific hormone, have all been implicated as mediators of
      impaired insulin sensitivity. The purpose of this study was to examine in
      patients with CHF and in comparison to healthy controls subjects whether
      norepinephrine, TNFalpha or leptin relate to insulin sensitivity. DESIGN: 41
      patients with CHF (age 60+/-2 years, NYHA I/II/III/IV 4/12/22/3, peak oxygen
      consumption 17.6+/-1.0 ml/kg per min) and 21 healthy controls of similar age and
      total and regional fat distribution were studied in a cross-sectional study.
      Insulin sensitivity was assessed by intravenous glucose tolerance testing using
      the minimal model approach; catecholamines, TNFalpha and soluble TNF receptors 1
      and 2 were also measured. Total and regional body fat mass was assessed by dual
      energy X-ray absorptiometry. RESULTS: Insulin sensitivity was reduced in CHF
      patients compared to controls by 31% (P<0.01) and fasting insulin was higher in
      patients than in controls (79.1+/-9.7 vs. 41.4+/-6.0 pmol/l, P<0.01). Patients
      had, compared to healthy controls, elevated serum leptin levels (8.28+/-0.84 vs.
      4.83+/-0.68 ng/ml), norepinephrine (3.45+/-0.34 vs. 1.87+/-0.16 nmol/l, both
      P<0.01) and soluble TNF-receptors 1 (1280+/-141 vs. 639+/-52 pg/ml) and 2 (2605+/
      184 vs. 1758+/-221 pg/ml, both P<0.01). Leptin levels corrected for total body
      fat mass were higher in CHF patients than in controls (41.3+/-3 vs. 24.3+/-2
      pg/ml per 100 g, P<0.001). TNFalpha was not significantly different between the
      groups. In both groups there was an inverse correlation between insulin
      sensitivity and serum leptin (r=-0.65, P<0.0001 for pooled subjects); in
      contrast, no significant relation was found between insulin sensitivity and
      norepinephrine or TNFalpha. In multivariate regression analysis, leptin emerged
      as the only significant predictor of insulin sensitivity (standardised
      coefficient=-0.59, P<0.001), independent of body fat mass, age and peak VO2.
      CONCLUSION: In moderate CHF, elevated leptin levels directly and independently
      predict insulin resistance. Elevated serum leptin levels could play a role in the
      impaired regulation of energy metabolism in CHF. In contrast to observations in
      other conditions, TNFalpha and norepinephrine are not related to insulin
      resistance in moderate CHF.

PMID- 11959388
TI  - Isolated pulmonary valve Pseudomonas aeruginosa endocarditis related to catheter
      embolism.

PMID- 11959390
TI  - Transient reversion of atrial fibrillation during an episode of digitalis
      toxicity.

PMID- 11959389
TI  - Magnetic resonance image (MRI) of an acquired aorto-pulmonary fistula, associated
      with cerebral and paradoxical embolism.
AB  - Aorto-pulmonary fistula has been described in Marfan's syndrome, with severe
      degeneration of connective tissue, particularly severe at the aortic site.
      Rarely, the chronic evolution of this condition could determine the formation of
      a fistula between the aorta and the adjacent anatomic structures [Ann Thorac Surg
      59 (1995) 1563; J Cardiovasc Surg 29 (1988) 403; Thorax 28 (1973) 521]. Here, we
      describe the first case of aorto-pulmonary fistula, with cerebral and paradoxical
      embolism, described with angio-nuclear magnetic resonance (MRI) of the heart.

PMID- 11959391
TI  - Low QRS voltage in cardiac tamponade: a study of 70 cases.

PMID- 11959392
TI  - Acute short-term effect of VVI pacing mode on P wave dispersion in patients with
      dual chamber pacemakers.
AB  - The acute or chronic effect of VVI pacing on P wave duration in the same patient
      with dual chamber pacemaker has not been studied before. Hence, with the purpose
      of determining whether VVI pacing increases dispersion of atrial refractoriness,
      we undertook a comparative study with the aid of a simple noninvasive approach,
      namely P wave dispersion (PWD) determined from surface electrocardiogram in the
      same patients who were implanted with dual chamber pacemakers. Pmax duration
      calculated in VVI paced mode was significantly higher than in VDD paced mode
      (121+/-21 vs. 111+/-17 ms, P=0.021). PWD (33+/-15 vs. 40+/-23 ms, P=0.062) did
      not demonstrate any significant difference between VDD and VVI paced modes,
      respectively. In conclusion, the findings of our study suggest that short-term
      VVI pacing itself does not have any direct effect on PWD in patients with dual
      chamber pacemakers. Different pacing modes in the long term might be responsible
      for altering PWD and the occurrence of atrial fibrillation while affecting the
      autonomic nervous system.

PMID- 11959394
TI  - Cyclooxygenase (COX)-2 and cell cycle activity in a transgenic mouse model of
      Alzheimer's disease neuropathology.
AB  - Prior studies have shown that cyclooxygenase (COX)-2, an enzyme involved in
      inflammatory mechanisms as well as neuronal activities, is up-regulated in the
      Alzheimer's disease (AD) brain and may represent a therapeutic target for anti
      inflammatory treatments. We report the effect of neuronal overexpression of human
      (h)COX-2 in a murine model of AD neuropathology. Transgenic mice expressing both
      the human amyloid precursor protein mutation (APPswe) and the human presenilin
      (PS1-A246E) mutation, with resultant AD plaque pathology, were crossed with
      transgenic mice expressing human (h)COX-2 in neurons. At 12 months of age, the
      APPswe/PS1-A246E/hCOX-2 triple-transgenic mice showed an elevation in the number
      of phosphorylated retinoblastoma (pRb) tumor suppressor protein and active
      caspase-3 immunopositive neurons, compared to double APPswe/PS1-A246E or single
      hCOX-2 transgenic controls. No detectable influence of neuronal hCOX-2 on AD
      neuropathology was found in the brain of APPswe/PS1-A246E/hCOX-2 triple
      transgenic mice, compared to double APPswe/PS1-A246E. In vitro studies revealed
      that hCOX-2 overexpression in primary cortico-hippocampal neurons derived from
      the hCOX-2 transgenics accelerates beta-amyloid (Abeta)(1-42)-mediated apoptotic
      damage which was prevented by the cell cycle dependent (CDK) inhibitor,
      flavoperidol. The data indicates that COX-2 overexpression causes alteration of
      neuronal cell cycle in a murine model of AD neuropathology, and provides a
      rational basis for targeting neuronal COX-2 in therapeutic research aimed at
      slowing the clinical progression of AD.

PMID- 11959395
TI  - FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition
      without APP overproduction.
AB  - To investigate the consequences of mutant presenilin-1 (PS-1) expression under
      the control of the normal PS-1 gene, a gene-targeted mouse bearing the FAD
      mutation P264L was made. Gene-targeted models are distinct from transgenic models
      because the mutant gene is expressed at normal levels, in the absence of the wild
      type protein. PS-1(P264L/P264L) mice had normal expression of PS-1 mRNA, but
      levels of the N- and C-terminal protein fragments of PS-1 were reduced while
      levels of the holoprotein were increased. When crossed into
      Tg(HuAPP695.K670N/M671L)2576 mice, the PS-1(P264L) mutation accelerated the onset
      of amyloid (Abeta) deposition in a gene-dosage dependent manner. Tg2576/PS
      1(P264L/P264L) mice also had Abeta deposition that was widely distributed
      throughout the brain and spinal cord. APP(NLh/NLh)/PS-1(P264L/P264L) double gene
      targeted mice had elevated levels of Abeta42, sufficient to cause Abeta
      deposition beginning at 6 months of age. Abeta deposition increased linearly over
      time in APP(NLh/NLh)/PS-1(P264L/P264L) mice, whereas the increase in Tg2576 mice
      was exponential. The APP(NLh/NLh)/PS-1(P264L/P264L) double gene-targeted mouse
      represents an animal model that exhibits Abeta deposition without overexpression
      of APP.

PMID- 11959396
TI  - Proinflammatory effects of M-CSF and A beta in hippocampal organotypic cultures.
AB  - Macrophage colony stimulating factor (M-CSF) is a microglial activator expressed
      at increased levels in the brain in Alzheimer's disease. In monotypic microglial
      cultures, M-CSF strongly augments amyloid beta (Abeta) induced microglial
      production of proinflammatory cytokines and nitric oxide. However, this
      augmentation could be due to strong autocrine and paracrine effects in monotypic
      cultures. We used hippocampal organotypic cultures to test M-CSF/Abeta
      augmentation in a system modeling intact brain. Combined M-CSF/Abeta treatment
      increased interleukin-1 (IL-1) and macrophage inflammatory protein 1-alpha
      expression by microglia, whereas inducible nitric oxide synthase (iNOS)
      expression was localized primarily to astroglia. Induction of cytokines and iNOS
      was also observed after lipopolysaccharide treatment of organotypic hippocampal
      cultures, but iNOS expression was localized mainly to microglia rather than
      astrocytes. Treatment with M-CSF/Abeta did not result in neuronal death. These
      results demonstrate that combined M-CSF/Abeta treatment results in a strong
      inflammatory response in the organotypic environment without inducing
      neurotoxicity.

PMID- 11959397
TI  - Cerebrospinal fluid tau in dementia disorders: a large scale multicenter study by
      a Japanese study group.
AB  - A large scale multicenter study of cerebrospinal fluid (CSF) tau levels was
      conducted to determine the cut-off value, sensitivity and specificity for
      clinical usage as a biomarker of Alzheimer's disease (AD). Its use for early and
      differential diagnosis and the factors that increase CSF tau levels were also
      examined. CSF samples from a total of 1,031 subjects including 366 patients with
      AD, 168 patients with non-Alzheimer type dementia (NA), 316 patients with non
      dementia neurological diseases (ND) and 181 normal controls (NC) were measured
      using ELISA for tau. The cut-off value of tau, 375 pg/ml, showed 59.1%
      sensitivity and 89.5% specificity for diagnosis of AD compared with the other
      groups. The tau levels were increased from the early to late stages of AD.
      Elevation of CSF tau in the non-tauopathy and tauopathy dementia groups, chronic
      and acute damage to the cerebrum, and meningeal disturbance were other factors
      that required attention for clinical practice. Measurement of CSF tau was useful
      as a biomarker for early and differential diagnosis of AD.

PMID- 11959398
TI  - Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in
      platelets and brain from patients with Alzheimer's disease.
AB  - Evidence suggests that mitochondrial dysfunction is prominent in Alzheimer's
      disease (AD). A failure of one or more of the mitochondrial electron transport
      chain enzymes or of F(1)F(0)-ATPase (ATP synthase) could compromise brain energy
      stores, generate damaging reactive oxygen species (ROS), and lead to neuronal
      death. In the present study, cytochrome c oxidase (COX) and F(1)F(0)-ATPase
      activities of isolated mitochondria from platelets and postmortem motor cortex
      and hippocampus from AD patients and age-matched control subjects were assayed.
      Compared with controls, COX activity was decreased significantly in platelets (
      30%, P < 0.01, n = 20) and hippocampus (-35 to -40%, P < 0.05, n = 6), but not in
      motor cortex from the AD patients. In contrast, in AD platelets and brain
      tissues, F(1)F(0)-ATP hydrolysis activity was not significantly changed.
      Moreover, the ATP synthesis rate was similar in mitochondria of platelets from AD
      patients and controls. These results demonstrate that COX but not F(1)F(0)-ATPase
      is a mitochondrial target in AD, in both a brain association area and in
      platelets. A reduced COX activity may make the tissue vulnerable to
      excitotoxicity or reduced oxygen availability.

PMID- 11959399
TI  - Distribution of plasma alpha 1-antichymotrypsin levels in Alzheimer disease
      patients and controls and their genetic controls.
AB  - Alzheimer's disease (AD) is a complex multifactorial disease in which many
      genetic and environmental factors are involved. Recent studies have shown that
      alpha(1)-antichymotrypsin (ACT) is one of the candidate genes for AD. Elevated
      levels of ACT have been widely, but not universally reported in the cerebrospinal
      fluid and plasma of AD patients. The genetic association between the ACT/codon 
      17*A allele of the signal peptide polymorphism and AD has been shown in some
      studies. One hypothesis is that the ACT/codon -17*A allele is in linkage
      disequilibrium with unknown functional mutation(s) in the ACT gene.
      Alternatively, the more hydrophobic character of the alanine (codon -17*A) may
      enhance ACT translocation into the endoplasmic reticulum and the Golgi apparatus,
      thus being secreted at higher levels. Therefore, this study was undertaken to
      determine the distribution of ACT plasma levels in cases (n = 397) and controls
      (n = 118) and the impact of ACT polymorphisms, including codon -17, on plasma ACT
      levels. In our cohort, plasma ACT levels were significantly higher in AD patients
      than controls (542.13 +/- 7.11 mg/liter vs. 496.62 +/- 12.79 mg/liter; P =
      0.002). The ACT/codon -17 polymorphism showed significant association with ACT
      levels in male AD patients, while the effect of the intron 4 polymorphism was
      significant in both male and female patients. Codon 227 polymorphism was
      associated with lower ACT levels in AD patients. In conclusion, ACT may play an
      important role in the AD pathogenesis and genetic variation in the ACT gene
      appears to have some effect on plasma ACT concentrations.

PMID- 11959400
TI  - The effect of increased concentrations of homocysteine on the concentration of
      (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with
      Alzheimer's disease.
AB  - There is evidence that increased blood concentrations of homocysteine may be a
      risk factor for Alzheimer's disease. (E)-4-hydroxy-2-nonenal (HNE) is a
      neurotoxic product of lipid peroxidation that is increased in the ventricular
      fluid and brains of patients with Alzheimer's disease. We measured the
      concentrations of homocysteine, HNE, vitamin B(12) and folate in the plasma of 27
      patients with Alzheimer's disease and 25 control subjects. There was a
      statistically significant increase in the plasma concentration of homocysteine (P
      < 0.001) and HNE (P < 0.001) in the Alzheimer's disease patients compared to the
      control group. There was a significant decrease in the plasma concentration of
      vitamin B(12) (P < 0.001) and folate (P = 0.002) in the Alzheimer's group
      compared to the controls. There was a significant positive correlation between
      the plasma concentrations of homocysteine and HNE in the patients with
      Alzheimer's disease (r = 0.661, P < 0.001). A significant negative correlation
      was found between the plasma concentration of homocysteine and the plasma
      concentrations of vitamin B(12) (r = -0.605, P = 0.0006) and folate (r = 0.586, P
      = 0.001). We also measured the concentrations of homocysteine, HNE, vitamin B(12)
      and folate in the cerebrospinal fluid (CSF) of 8 patients with Alzheimer's
      disease compared to 6 control subjects. The concentrations of homocysteine (P =
      0.032) and HNE (P = 0.001) were significantly higher in the CSF of Alzheimer's
      patients than in the control subjects. There were significant positive
      correlations between the CSF concentrations of homocysteine and HNE (r = 0.924, P
      = 0.001). There was also a significant positive correlation between the plasma
      concentration of homocysteine and the CSF concentrations of homocysteine (r =
      0.850, P = 0.007) and HNE (r = 0.092, P = 0.002). These results demonstrate that
      there is a relationship between increased homocysteine concentrations and
      increased HNE concentrations in Alzheimer's disease.

PMID- 11959401
TI  - Inositol monophosphatase activity in normal, Down syndrome and dementia of the
      Alzheimer type CSF.
AB  - Inositol monophosphatase (IMPase), a cytoplasmic enzyme that hydrolyses inositol
      monophosphates to produce inositol is also found in the cerebrospinal fluid
      (CSF). Since levels of inositol have been previously reported to be elevated in
      Down syndrome (DS) CSF, IMPase activity was measured in CSF of DS subjects to
      establish whether altered inositol levels may be related to changes in IMPase
      activity. In addition, and to better understand the regulation of IMPase
      expression in the CSF, enzyme activity was measured in normal aging, patients
      with Alzheimer-type or multi-infarct dementia (DAT and MID, respectively) and in
      CSF obtained by repeat lumbar puncture or from sequential aliquots of CSF from
      along the rostro-caudal axis. IMPase activity was relatively constant in CSF
      obtained from repeated lumbar puncture and there was no significant rostro-caudal
      gradient of activity in either normal or DS subjects, indicating that the enzyme
      originates from both brain and spinal cord. Compared to respective age-matched
      normal subjects, CSF IMPase activity was unaltered in DS, DAT and MID. However,
      in normal volunteers there was a significant positive correlation between age and
      CSF IMPase activity. Furthermore, there were significant correlations between CSF
      IMPase activity and acetylcholinesterase and butyrylcholinesterase activities and
      total protein, suggesting co-regulation of these parameters within the CSF.

PMID- 11959402
TI  - Taste, smell and neuropsychological performance of individuals at familial risk
      for Alzheimer's disease.
AB  - The purpose of the study was to determine whether there are chemosensory and
      neuropsychological changes that predate the onset of Alzheimer's disease in
      individuals at enhanced risk of developing the condition. To study this question,
      a unique sample of individuals (n = 33) was studied who were genetically at-risk
      for AD by virtue of documented multigenerational evidence of the disease (so
      called multiplex families). The performance of at-risk individuals was evaluated
      on various smell, taste, and neuropsychological measures at baseline and 18
      months later. Their performance was compared to a control group (n = 32) that was
      matched in age, gender, education, and race. At baseline the at-risk group
      performed worse than the control group on the chemosensory measures of phenethyl
      alcohol smell detection, smell memory, and taste memory, and on a memory measure
      involving recall of narrative information (Logical Memory I from the Wechsler
      Memory Scale- Revised). Across both sessions, the at-risk group had lower smell
      memory scores than the control group. At-risk status was not significantly
      associated with APOE status. The results of this and other studies suggest that
      individuals who are genetically at risk for developing AD may perform more poorly
      on memory and smell measures compared to those not at risk. This effect may be
      separate from one known genetic risk factor of AD, APOE, and supports that
      multiple genes are likely responsible for the disease and its associated memory
      and other neurocognitive symptoms.

PMID- 11959403
TI  - Substitution at codon 22 reduces clearance of Alzheimer's amyloid-beta peptide
      from the cerebrospinal fluid and prevents its transport from the central nervous
      system into blood.
AB  - A point mutation of G to C at codon 693 of the amyloid-beta (Abeta) precursor
      protein gene results in Glu to Gln substitution at position 22 of the Abeta
      (AbetaQ22) associated with hereditary cerebrovascular amyloidosis with hemorrhage
      Dutch type. Factors that regulate AbetaQ22 levels in the central nervous system
      (CNS) are largely unknown. By using ventriculo-cisternal perfusion technique in
      guinea pigs, we demonstrated that clearance from the cerebrospinal fluid and
      transport from the CNS to blood of [(125)I]-AbetaQ22 (1 nM) were reduced by 36%
      and 52%, respectively, in comparison to the wild type Abeta(1-40) peptide. In
      contrast to significant uptake and transport of Abeta(1-40) across the brain
      capillaries and leptomeningeal vessels, AbetaQ22 was not taken up at these CNS
      vascular transport sites, which was associated with its 53% greater accumulation
      in the brain. The CNS clearance of Abeta(1-40) was half-saturated at 23.6 nM;
      AbetaQ22 had about 6.8-fold less affinity for the CNS efflux transporters and its
      elimination relied mainly on transport across the choroid plexus. Thus, the Dutch
      mutation impairs elimination of Abeta from brain by reducing its rapid transport
      across the blood-brain barrier and the vascular drainage pathways, which in turn
      may result in accumulation of the peptide around the blood vessels and in brain.

PMID- 11959404
TI  - A bivariate genetic analysis of cerebral white matter hyperintensities and
      cognitive performance in elderly male twins.
AB  - White matter hyperintensities (WMHs) are frequently observed on MRI scans of
      elderly nondemented people and have been associated in the past with cognitive
      impairment and physical dysfunction. Individual differences in the prevalence and
      severity of WMHs have been documented and more recently we reported on the
      significant contribution of genetic influences to this variability. The objective
      of the present study was to further investigate, in the context of a behavioral
      genetic paradigm, the nature of the association between WMHs and cognitive and
      physical function. MRI brain scans and a battery of neuropsychological and
      physical function tests were given to 142 male-male twin pairs [72 monozygotic
      (MZ) and 70 dizygotic (DZ)], participants in the 4th exam of the NHLBI Twin
      Study. Biometric genetic modeling was used to estimate the genetic and/or
      environmental covariation between WMHs and cognitive and physical summary scores.
      The phenotypic association between WMHs and cognitive function in this sample of
      twins was modest but statistically significant. Genetic analyses of cognitive and
      physical function summary scores found that 55% to 70% of the observed
      variability was due to genetic influences. A further decomposition of the
      phenotypic association between WMHs and cognitive function found that 70% to 100%
      of the phenotypic covariation was due to common genetic effects. Similar results
      explained the association between WMHs and performance on two physical function
      tests. We conclude from these analyses that common genetic influences explain to
      a large extent previously observed phenotypic associations between large amounts
      of WMHs and poor cognitive and physical function in the elderly.

PMID- 11959405
TI  - The microvascular frontal-subcortical syndrome of aging.
AB  - Many features of aging suggest dysfunction in both frontal and subcortical
      regions. Connections between the two areas form a series of pathways that
      critically influence various aspects of cognition, motor control, affect, and as
      recently discovered, normal urinary function. Age-related changes in the
      structure and integrity of these circuits may be associated with cognitive
      impairment, mood disorders, loss of balance, falls, and urinary dysfunction. In
      addition, cardiovascular risk factors in elderly people are associated with the
      development of cerebral microangiopathic changes in both the periventricular
      white matter and basal ganglia. These lesions are common, usually unsuspected,
      and were previously believed to be clinically innocuous. However, increasing
      evidence supports a role for these lesions as a cause for both dysfunction in
      frontal-subcortical systems, and many clinical features of aging that account for
      substantial disability. Because this form of cerebrovascular disease is
      potentially preventable, interventions that address risk factors for the
      development of cerebral microangiopathy may go a long way in preventing
      disability for the next generation of elderly persons.

PMID- 11959406
TI  - Normal aging in the central nervous system: quantitative MR diffusion-tensor
      analysis.
AB  - The purpose of this study is to elucidate changes in mean diffusivity (ADC) and
      fractional anisotropy (FA) using MR diffusion tensor imaging (DTI) in the central
      nervous system during normal aging. We studied 50 normal volunteers (30 men, 20
      women; mean age 44.8 +/- 14.0; age range, 21-69 years) without disorders
      affecting the central nervous system. The frontal, parietal white matter,
      lentiform nucleus, posterior limb of internal capsule, thalamus, genu and
      splenium of the corpus callosum were selected for investigation. There was no
      significant difference in ADC or FA between male and female or between the right
      and left hemisphere. A significant ADC increase with advancing age was observed
      in frontal white matter (P = 0.010) and lentiform nucleus (P = 0.022). A
      significant FA decline was found only in the genu of the corpus callosum (P <
      0.001) with advancing age. Quantitative diffusion tensor analysis correlate with
      normal aging and may help in assessing normal age-related changes and serve as a
      standard for comparison with neurodegenerative disorders.

PMID- 11959407
TI  - Age-related changes in neural trace generation of rule-based auditory features.
AB  - Young (M = 22) and elderly volunteers (M = 74) participated in an ERP study that
      examined rule-based feature ion in the auditory modality. Stimuli were either a
      frequent ascending tone pair or an infrequent descending tone pair. Tone-pairs
      were presented under three conditions. Physical feature monaural (1 tone pair),
      feature monaural (10 tone pairs), and feature binaural (10 tone pairs).
      Volunteers watched a silent movie during ERP recordings. After completion of the
      ERP session all volunteers participated in a behavioral discrimination task. MMNs
      were elicited under all three conditions for the young. For the elderly, MMNs
      were elicited under both monaural conditions but not under binaural conditions.
      Behavioral discrimination was high under the physical feature condition but fell
      to near chance under the two rule-based feature conditions for both age groups.
      Thus rule-based neural representations were generated for both age groups under
      monaural conditions, but only for the young under binaural conditions, suggesting
      that there is an age-related decline in the efficacy of integrating multiple
      sources into a single auditory stream.

PMID- 11959408
TI  - Comparison of maternal separation and early handling in terms of their
      neurobehavioral effects in aged rats.
AB  - In the rat, relative to pup nonhandling (NH), early handling (EH) leads to old
      adult offspring with a hyporesponsive HPA axis, superior spatial cognition, and
      greater hippocampal (HIPP) neuronal density. The present study compared the
      effects of EH and repeated maternal separation (MS), in the form of 6-hr
      separation on each of 4 days beginning at day 12, on spatial cognition,
      corticosterone (CORT) levels, and HIPP characteristics, in aged rats. Male Wistar
      rat pups were exposed to EH, MS, NH or our normal in-house husbandry (CON) and
      tested at 18-20 months. Relative to NH and CON, EH demonstrated superior spatial
      cognition, reduced CORT stress response, reduced CA-field volume and no change in
      HIPP neuronal number. MS demonstrated a trend to superior spatial cognition, an
      unaffected CORT stress response, reduced CA-field volume and no change in HIPP
      neuronal number. These findings are important in terms of the life-span
      mechanisms via which postnatal manipulations induce neurobehavioral effects, and
      the mechanisms via which CORT and HIPP structure relate to HIPP function.

PMID- 11959409
TI  - Interactions between aging and cortical cholinergic deafferentation on attention.
AB  - Pre-existing trauma to basal forebrain corticopetal cholinergic neurons has been
      hypothesized to render this system vulnerable to age-related processes. The
      present longitudinal study assessed the interactions between the effects of
      partial cortical cholinergic deafferentation and aging on sustained attention
      performance. After pre-surgical training, animals were given sham-surgery or
      bilateral infusions of the immunotoxin 192 IgG-saporin into the basal forebrain.
      The lesion was intended to yield a limited loss of cortical cholinergic inputs
      and thus to produce minor immediate effects on sustained attention performance.
      All animals were tested continuously until age 36 months. The attentional
      performance of lesioned and sham-lesioned animals did not dissociate until age 31
      months, when the lesioned animals exhibited an impairment in overall sustained
      attention performance. Importantly, this impairment interacted with the effects
      of time-on-task, and thus reflected a specific impairment in attentional
      processes. These results support the notion that pre-existing damage to the basal
      forebrain corticopetal cholinergic neurons yields age-related impairments in the
      attentional capabilities that depend on the integrity of this neuronal system.

PMID- 11959410
TI  - No effect of age and estrogen on aromatic L- amino acid decarboxylase activity in
      rhesus monkey brain.
AB  - A variety of studies have shown an effect of estrogen on dopamine function and
      suggest that estrogen may modulate central dopaminergic activity. Positron
      emission tomography (PET) and the dopamine metabolism tracer, [18F]6-fluoro-L-m
      tyrosine (FMT) were used to evaluate dopaminergic function in the frontal cortex
      and striatum in six aged, but pre-menopausal, female monkeys before and after
      ovariectomy (OVX). Dynamic PET brain uptake data and metabolite-corrected blood
      input functions were fit to a three-compartment model for FMT uptake. Prior to
      OVX, all animals showed preferential accumulation of the tracer bilaterally in
      the striatum and less but measurable activity in the frontal cortex. Paired
      comparisons showed that there were no significant differences in FMT uptake
      (K(i)) in either brain region before and after OVX. In addition, FMT uptake did
      not differ from a group of young adult female monkeys at either time point. These
      findings may represent a compensatory up-regulation of aromatic L- amino acid
      decarboxylase (AADC) activity.

PMID- 11959411
TI  - Does postural instability affect the initiation of human gait?
AB  - During gait initiation (GI), decoupling of the center of mass and center of
      pressure allows the center of mass to fall forwards. Subjects initiated gait
      rapidly before and after tibial nerve block of the tibial nerve. Static single
      limb stability, stance limb ground reaction forces, electromyogram and temporal
      data were measured. It was hypothesized that postural stability would decrease
      post-block and that this would affect the kinetic and temporal properties of GI.
      Subjects had significantly decreased postural stability post-block and changes in
      normal gait kinetics, however, no changes were noted in ground reaction forces or
      relative temporal data of the GI task. The finding that GI was unaffected by
      diminished single leg postural instability suggests that GI is a pre-programmed
      task.

PMID- 11959412
TI  - Dorsal horn synaptosomal content of aspartate, glutamate, glycine and GABA are
      differentially altered following chronic constriction injury to the rat sciatic
      nerve.
AB  - The present study directly examined the axon terminal (synaptosomal) level of
      amino acid neurotransmitters in rats following chronic constriction injury (CCI)
      to the sciatic nerve. Dorsal horn, synaptosomal content of aspartate (Asp),
      glutamate (Glu), glycine and gamma-aminobutyric acid (GABA) was assessed in these
      rats, and in normal age-matched and younger rats. The synaptosomal content of Asp
      and Glu in CCI rats was increased by 44-46% compared with control rats (P<0.016).
      The synaptosomal content of GABA in younger rats was 33% lower than that observed
      in control rats (P<0.005). Altered axon terminal levels of amino acid
      neurotransmitters accompany the painful symptoms of neuropathy. The lower axon
      terminal level of GABA in younger rats may help to explain the age-dependency of
      pain development in animal models of nerve injury.

PMID- 11959413
TI  - Egestive feeding responses in Aplysia persist after sectioning of the cerebral
      buccal connectives: evidence for multiple sites of control of motor programs.
AB  - Ingestive and egestive behaviors in Aplysia are generated by motor neurons and
      interneurons chiefly located in the buccal ganglion, but cerebral ganglion
      neurons appear to contribute to both ingestive and egestive motor programs. We
      investigated if the cerebral ganglion input to the buccal ganglion is necessary
      for the generation of buccal ingestive and egestive behaviors in free-moving
      animals. We confirmed a prior study that showed that animals with lesions of the
      cerebro-buccal connectives (CBCs) do not exhibit rhythmic biting following
      seaweed stimulation of the lips, but do show swallowing of seaweed inserted into
      the buccal cavity. We found that CBC-lesioned animals also exhibited rejection of
      a tube inserted into the buccal cavity and esophagus. The programs for swallowing
      and rejection behaviors were similar to those observed before lesioning the CBCs,
      although the rate of swallowing was slower. These results suggest that the
      cerebral input to the buccal ganglion is necessary for generating biting
      responses, but is not required for producing swallowing or rejection responses.

PMID- 11959415
TI  - Initiation of a vertical jump: the human body's upward propulsion depends on
      control of forward equilibrium.
AB  - The aim of the study was to understand: (i), how far anticipatory postural
      adjustments (APA) participate in the sequences of a complex task; (ii), how, in
      the sagittal plane, horizontal and vertical progressions of the center of gravity
      (CG) are managed to achieve the prescribed goal. A posturo-kinetics sequence is
      identified during which forward CG progression is controlled in terms of a center
      of pressure (CP)-CG interaction. CP shifts and horizontal CG accelerations are
      correlated in timing and amplitude. There exists a control of whole body
      progression during the impulse, implying a braking of forwards movement. Vertical
      and horizontal CG accelerations are inter-dependent, and backward CP shift
      duration is related to its forward displacement. During the vertical jump
      initiation, whole body vertical propulsion and forward fall are linked. To
      increase impulse amplitude, initial whole body disequilibrium is lengthened and
      forward CG acceleration is greater. APA programming is probably elaborated on the
      basis of cognitive evaluation of the antero-posterior disturbance.

PMID- 11959414
TI  - Stimulatory effects of pituitary adenylate cyclase-activating polypeptide on
      inositol phosphates accumulation in avian cerebral cortex and hypothalamus.
AB  - This study has demonstrated that the short and long form of the pituitary
      adenylate cyclase-activating polypeptide (PACAP), i.e. PACAP(27) and PACAP(38),
      moderately but significantly, and in a concentration (0.5-5 microM)-dependent
      manner, stimulated inositol phosphates (IPs) accumulation in myo-[(3)H]inositol
      prelabeled cerebral cortical and hypothalamal slices of chick and duck, and in
      slices of rat cerebral cortex; both peptides had no effect on IPs formation in
      rat hypothalamus. Vasoactive intestinal peptide (VIP; 0.5-5 microM) weakly
      enhanced IPs accumulation in chick hypothalamus, had no significant action in
      chick cerebral cortex (in fact there was a tendency to attenuate the IPs response
      in this tissue), and slightly, but significantly, inhibited the IPs accumulation
      in rat cerebral cortex. VIP showed no activity in rat hypothalamus. It is
      concluded that the stimulatory action of PACAP on phosphoinositide metabolism in
      avian cerebral cortex, similar to rat cerebral cortex, is mediated via
      phospholipase C-linked PAC(1) type receptors. In chick hypothalamus, however,
      there may be a component of VPAC type receptors stimulating IPs formation.

PMID- 11959416
TI  - Amplitude of somatosensory cortical evoked potentials is correlated with
      spontaneous activity of spinal neurones in the cat.
AB  - Simultaneous recordings of cortical evoked potentials in the posterior sigmoid
      gyrus, and spontaneous negative cord dorsum potentials (CDPs) of the L6 lumbar
      spinal segment, were made in the anaesthetised cat. The electrodes were
      positioned in cortical and spinal somatosensory regions where the largest
      spontaneous and evoked negative potentials were detected. Evoked potentials were
      produced by electrical stimulation to cutaneous nerves or by mechanical
      stimulation of the hindpaw skin. We found that both electrically and mechanically
      cortical evoked potentials were facilitated during the spontaneous negative CDPs.
      The magnitude of such facilitation was proportional to the amplitude of the
      'conditioning' spontaneous negative CDPs. This led to a high positive correlation
      between amplitude fluctuations of spontaneous negative CDPs and fluctuations of
      the cortical evoked potentials. This observation suggests that transmission of
      cutaneous sensory information in ascending pathways could be facilitated when
      dorsal horn spinal neurones are active.

PMID- 11959417
TI  - Equine estrogens induce apolipoprotein E and glial fibrillary acidic protein in
      mixed glial cultures.
AB  - Premarin, which contains several equine estrogens, as well as estradiol (E2) as a
      minor component, is widely used for replacement therapy of estrogen deficits, but
      little is known of its direct actions on brain cells. In mixed glial cultures,
      apolipoprotein E (apoE) and glial fibrillary acidic protein (GFAP) are induced by
      estrogens. GFAP induction showed an inverted-U shape E2 dose response, with a
      maximum induction at 1 pM, whereas apoE mRNA induction was greatest at 100 pM.
      GFAP and ApoE mRNAs were induced by equine estrogens in the following order:
      E2=equilin>estrone>17 alpha-dihydroequilenin. However, the induction of apoE
      secretion by 17 alpha-dihydroequilenin was as effective as by the other
      estrogens. The greater response of apoE secretion than GFAP mRNA induction to 17
      alpha-dihydroequilenin might be therapeutically important because of the glial
      scarring during brain lesions, in which GFAP induction has a major role in
      inhibiting neurite outgrowth, whereas apoE secretion supports neurite outgrowth.

PMID- 11959419
TI  - Expression of super cervical ganglion-10 (SCG-10) mRNA in the monkey cerebral
      cortex during postnatal development.
AB  - We used Northern blot analysis to measure SCG10 mRNA expression in various areas
      of the monkey cerebral cortex during postnatal development. In all areas, SCG10
      mRNA expression was highest immediately after birth, decreased sharply until
      postnatal day 70 (P70) and then decreased slowly until the adult stage.
      Expression levels were similar in all areas at all time points during
      development, including the adult stage. These findings confirm that axonal growth
      in the monkey cerebral cortex is most vigorous before or during the perinatal
      period, progresses similarly in all areas until P70, and continues at lower
      levels during late development.

PMID- 11959418
TI  - Daily rhythm of glutathione peroxidase activity, lipid peroxidation and
      glutathione levels in tissues of pinealectomized rats.
AB  - Melatonin is a component of the antioxidant defense system since it has radical
      scavenging and antioxidant activities. In the present study, we aimed to
      investigate the endogenous rhythm of antioxidant enzyme glutathione peroxidase
      (GSH-Px) activity, oxidized glutathione (GSSG) and lipid peroxidation levels in
      tissues of pinealectomized rats (PINX). Rats were sacrificed by decapitation at 4
      h intervals. GSH-Px activity, GSSG and lipid peroxidation levels showed a daily
      rhythm both in controls and in PINX rats. GSH-Px and GSSG exhibited the peak
      levels after the peak time of melatonin which was determined previously by other
      groups. Lipid peroxidation levels increased progressively during the night and
      started to decline before the GSH-Px peak time. These findings suggest that
      endogenous melatonin is involved in the night time increase of GSH-Px activity
      and GSSG levels and modulates the daily rhythm pattern of GSH-Px. In conclusion,
      pinealectomy which eliminates the melatonin rhythm has a supressor effect on GSH
      Px activity levels.

PMID- 11959420
TI  - Functional characterizations of cocaine- and amphetamine-regulated transcript
      mRNA expression in rat hypothalamus.
AB  - Anatomical relationships of hypothalamic cocaine- and amphetamine-regulated
      transcript (CART) with other hypothalamic neuropeptides were examined by using in
      situ hybridization histochemistry and immunohistochemistry. CART mRNA was found
      in various regions in rat hypothalamus, including the periventricular nucleus,
      paraventricular nucleus, dorsomedial nucleus, perifornical regions, lateral
      nucleus, and the arcuate nucleus. In the paraventricular nucleus, CART mRNA is
      colocalized with vasopressin and corticotropin-releasing factor-containing
      neurons. Moreover, either fasting or diabetes attenuates CART mRNA expression in
      the hypothalamus, demonstrating that CART mRNA regulation is related to the fuel
      availability and peripheral hormonal status. Our findings suggest that the
      presence of CART mRNA in specific cell groups of the hypothalamus plays a role in
      hypothalamic regulation of neuroendocrine functions.

PMID- 11959421
TI  - Effects of near-infra-red laser irradiation on adenosine triphosphate and
      adenosine diphosphate contents of rat brain tissue.
AB  - Low-power, near-infra-red laser irradiation has been used to relieve patients
      from various kinds of pain, though the precise mechanisms of such biological
      actions of the laser have not yet been resolved. To investigate the cellular
      mechanisms by near-infra-red laser on the nervous system, we examined the effect
      of 830-nm laser irradiation on the energy metabolism of the rat brain. The diode
      laser was applied for 15 min with an irradiance of 4.8 W/cm(2). Tissue adenosine
      triphosphate (ATP) content of the irradiated area in the cerebral cortex was 19%
      higher than that of the non-treated area, whereas the adenosine diphosphate (ADP)
      content showed no significant difference. Laser irradiation at another wavelength
      (652 nm) had no effect on either ATP or ADP contents. The temperature of the
      tissue was increased by 4.4-4.7 degrees C during the irradiation of both
      wavelengths. These results suggest that the increase in tissue ATP content did
      not result from the thermal effect, but from a specific effect of the laser
      operated at the 830-nm wavelength.

PMID- 11959422
TI  - Effect of cyclopiazonic acid on membrane currents in isolated inner hair cells
      from guinea-pig cochlea.
AB  - Cyclopiazonic acid (CPA) is a reticulum-like intracellular Ca(2+) store
      depletory, which raises intracellular Ca(2+) concentration. The effect of CPA on
      membrane currents in isolated inner hair cells (IHCs) from guinea-pig cochlea was
      investigated by the patch-clamp technique in the whole-cell configuration. Four
      out of eight IHCs showed an augmentation of the currents and the other four cells
      showed an inhibition of the currents by extracellular CPA application. The
      activation kinetics of outward currents were not changed by CPA. Three out of
      four IHCs obtained from the basal part of the cochlea demonstrated augmentation,
      whereas three out of four IHCs from the apical part demonstrated inhibition of
      the currents. This result suggests that Ca(2+)-activated currents were dominant
      in the basal IHCs of the cochlea.

PMID- 11959423
TI  - Expanded polyglutamine stretches form an 'aggresome'.
AB  - To understand the pathogenetic mechanisms underlying polyglutamine (polyQ)
      diseases, we investigated the mechanisms of the formation of aggregate bodies
      containing expanded polyQ stretches, focusing on dentatorubral-pallidoluysian
      atrophy (DRPLA). We demonstrated that the expression of a truncated DRPLA protein
      containing expanded polyQ stretches in COS-7 cells resulted in the formation of
      perinuclear aggregate bodies that are co-localized with gamma-tubulin, a protein
      marker for the microtubules-organizing center (MTOC). A collapsed vimentin
      network surrounded these aggregate bodies. Furthermore, disruption of the
      microtubules (MTs) with nocodazole resulted in the formation of small aggregate
      bodies that were scattered throughout the cytoplasm. These findings suggest that
      the truncated DRPLA proteins containing expanded polyQ stretches unfold and form
      small aggregate bodies in the cell periphery. These aggregates move on MTs to the
      MTOC, where they remain as distinct 'aggresomes''.

PMID- 11959424
TI  - An alternatively spliced form of rodent alpha-synuclein forms intracellular
      inclusions in vitro: role of the carboxy-terminus in alpha-synuclein aggregation.
AB  - In the rat, the -synuclein gene is alternatively spliced and exists in three
      forms, rat synuclein 1 (rSYN1), synuclein 2 (rSYN2) and synuclein 3. rSYN2 cDNA
      encodes a 149 amino acid protein that is homologous to rSYN1 and human -synuclein
      for the first 100 amino acids, but is divergent for the 49 amino acid carboxy
      terminal region. We demonstrate here that rSYN2 forms small aggregates throughout
      the cytoplasm when overexpressed in human H4 cells, whereas rSYN1 expression is
      diffuse. Inhibition of the proteasome promotes the formation of larger,
      cytoplasmic rSYN2 inclusions in transfected cells. Although a survey of the
      available databases suggests that there is no human splice form equivalent of
      rSYN2, thus arguing against a direct role in Lewy body formation and Parkinson's
      disease, these data nonetheless suggest that modifications of the carboxy
      terminal region of -synuclein predispose it to inclusion formation.

PMID- 11959425
TI  - Presence of the N-methyl-D-aspartic acid R1 glutamatergic receptor subunit in the
      lumbosacral spinal cord of male rats.
AB  - The lumbosacral spinal cord contains neurones that control the lower urogenital
      and digestive tracts. Spinal neurones respond to activation from the periphery
      and supraspinal nuclei. Glutamate, acting through a variety of receptors, is an
      established transmitter of excitatory pathways to the spinal cord. Using
      immunohistochemical methods, we reveal the presence of the N-methyl-D-aspartic
      acid R1 (NMDAR1) glutamatergic receptor subunit in the lumbosacral spinal network
      that controls urogenital and digestive functions: the dorsal horn; the area
      around the central canal including the dorsal grey commissure; the sacral
      parasympathetic nucleus; and pudendal motoneurones. A complete thoracic spinal
      section did not alter labelling. Using retrograde labelling techniques, we
      identify sacral preganglionic neurones and pudendal neurones that are NMDAR1
      immunoreactive. Glutamate, acting at NMDA receptors, can therefore co-ordinate
      the activity of the autonomic and somatic outflows to the pelvic organs.

PMID- 11959426
TI  - Polymorphisms of chromogranin B gene associated with schizophrenia in Chinese Han
      population.
AB  - Chromogranin is a widespread family of proteins in the neurosystem, whose
      function is guiding the sorting and secretion of neuropeptides. Using functional
      and positional evidences, chromogranin B was selected as a candidate gene for
      schizophrenia. We systematically screened all the promoter and exon regions of
      the gene and detected 15 single nucleotide polymorphisms (SNPs), among which four
      SNPs (including two non-synonymous SNPs) were selected for association analysis.
      In a cohort of Chinese Han schizophrenia cases and controls, the results of both
      the individual SNPs and the haplotypes of SNPs were significantly positive
      (P<0.01). Our results confirm the role of neuropeptides in the pathogenesis of
      schizophrenia.

PMID- 11959427
TI  - Measurement of 5-hydroxytryptamine release in the rat medial vestibular nucleus
      using in vivo microdialysis.
AB  - The function of the 5-hydroxytryptamine (5-HT) system in the medial vestibular
      nucleus (MVN) was evaluated using KCl-evoked 5-HT release assessed by in vivo
      microdialysis. The release of 5-HT in the MVN was increased by the local
      application of KCl (100 mM) in a calcium-dependent manner. Likewise, perfusion of
      a 5-HT reuptake blocking agent, clomipramine (1 microM), increased extracellular
      levels of 5-HT in the MVN. Finally, pretreatment with the selective 5-HT(1A)
      agonist, 8-hydroxy-2-(di-N-propylamino) tetralin (1 mg/kg, intraperitoneally),
      attenuated the KCl-evoked 5-HT release. These findings suggest that 5-HT stored
      in vesicles is released from nerve terminals in the MVN. In addition, its
      regulation may be mediated by control of somatodendritic 5-HT(1A) receptor
      activation.

PMID- 11959428
TI  - Hypotonic medium increases calcium permeant channels activity in human normal and
      dystrophic myotubes.
AB  - Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin
      and an elevated intracellular calcium level. Single-channel recordings were
      performed with the cell-attached configuration of the patch-clamp technique. The
      present study shows, on human co-cultured normal and dystrophic muscle cells, the
      evidence for an increased activity of calcium permeant cationic mechano-sensitive
      channels under hypotonic medium stimulation. This activity was particularly
      enhanced in DMD cells. The hypotonic medium induced drastic changes in the single
      channel activity characteristics, which are: a large increase of the calcium over
      potassium permeability ratio; and a great enhancement of the quantity of current
      crossing through these channels. These channels could contribute to a significant
      calcium entry, which could participate in the abnormal calcium homeostasis
      observed in DMD muscle.

PMID- 11959429
TI  - Expression of highly polysialylated neural cell adhesion molecule in rat
      subventricular zone with exposure to repeated kindled seizures.
AB  - Immunoreactive highly polysialylated neural cell adhesion molecule (PSA-NCAM)
      expression was examined in the rat with repeated exposure to amygdaloid kindled
      generalized seizures (GS). In the sham control brain, PSA-NCAM staining was
      slightly observed in the subventricular zone (SVZ) of the striatum. The number of
      PSA-NCAM positive cells increased four times in the bilateral SVZ after three
      consecutive GS, with a further increase after 30 consecutive GS. As PSA-NCAM is
      involved in neural plasticity as well as migration of neural stem cells (NSC),
      expression of PSA-NCAM in the SVZ suggests that the recurrent GS may mainly
      contribute to reconstruction of synaptic network and could also contribute to NSC
      migration after kindling.

PMID- 11959430
TI  - Rhizobial acyl carrier proteins and their roles in the formation of bacterial
      cell-surface components that are required for the development of nitrogen-fixing
      root nodules on legume hosts.
AB  - Acyl carrier protein (ACP) of Escherichia coli is a small acidic protein which
      functions as carrier of growing acyl chains during their biosynthesis and as
      donor of acyl chains during transfer to target molecules. This unique ACP of E.
      coli is expressed constitutively. In more complex bacteria, multiple ACPs are
      present, indicating a channeling of pools of multi-carbon units into different
      biosynthetic routes. In rhizobia, for example, besides the constitutive ACP
      (AcpP) involved in the biosynthesis and transfer of common fatty acids, three
      specialized ACPs have been reported: (1) the flavonoid-inducible nodulation
      protein NodF, (2) AcpXL that transfers 27-hydroxyoctacosanoic acid to a sugar
      backbone during lipid A biosynthesis, and (3) the RkpF protein which is required
      for the biosynthesis of rhizobial capsular polysaccharides. All three of those
      specialized rhizobial ACPs are required for the biosynthesis of cell-surface
      molecules that play a role in establishing the symbiotic relationship between
      rhizobia and their legume hosts. Surprisingly, the recently sequenced genomes
      from Mesorhizobium loti and Sinorhizobium meliloti suggest even more candidates
      for ACPs in rhizobia.

PMID- 11959431
TI  - Transposon Tn1721 distribution among strains of Xylella fastidiosa.
AB  - Transposons are mobile genetic elements found within the genomes of various
      organisms including bacteria, fungi, plants and animals. Fragments of the
      transposon Tn1721 were found included in the genome of Xylella fastidiosa strain
      9a5c. Regions from such fragments were PCR-amplified using specially designed
      primers (TNP(1) and TNP(2)). In order to detect insertions of the Tn1721 element,
      both primers were used and one of them included a region of the transposon
      (TNP(1)) and the other one had the right repeat and part of the bacterial
      chromosome (TNP(2)). The PCR products obtained from strain 9a5c were used as a
      pattern for fragment size comparisons when DNA samples from other X. fastidiosa
      strains were used as template for the PCR assays. Differences were observed
      concerning the PCR products of such amplifications when some X. fastidiosa
      strains isolated from grapevine and plum were used. For the citrus-derived
      strains only the strains U187d and GP920b produced fragments with different sizes
      or weak band intensity. Such variations in the X. fastidiosa genome related to
      disrupted Tn1721 copies are probably due to the possibility of such a transposon
      element being still able to duplicate even after deletion events might have taken
      place and also because the bacterial strains in which the main differences were
      detected are derived from different host plants cultivated under different
      climate conditions from the one used as reference.

PMID- 11959432
TI  - Chitin synthesis during in planta growth and asexual propagation of the
      cellulosic oomycete and obligate biotrophic grapevine pathogen Plasmopara
      viticola.
AB  - PCR amplification of two CHS gene fragments of the obligate biotroph Plasmopara
      viticola, the causal agent of downy mildew of grapevine, is described. While one
      fragment shows homology to fungal class IV chitin synthases, the other fragment
      groups with other oomycete chitin synthases to form a novel class of chitin
      synthases most closely related to class I-III. RT-PCR experiments indicate that
      PvCHS1 is constitutively expressed, whereas PvCHS2 is specifically transcribed in
      sporangiophores and sporangia. Analyses of wheat germ agglutinin labeling
      patterns by confocal laser scanning microscopy show that chitin is present on the
      surface of hyphal cell walls during in planta growth, and of sporangiophores and
      sporangia.

PMID- 11959433
TI  - Oral colonization and immune responses to Streptococcus gordonii expressing a
      pertussis toxin S1 fragment in mice.
AB  - The ability of a recombinant Streptococcus gordonii RJM4 expressing the N
      terminal 179-amino acid fragment of S1 subunit of pertussis toxin (PT) as a
      SpaP/S1 fusion protein was tested for oral colonization and immunogenicity in
      BALB/c mice. Following two consecutive oral inoculations, 100% of the mice were
      colonized by the recombinant strains for up to 9 weeks and >60% of the animals
      still retained the strains after 19 weeks. RJM4 recovered from the animals
      continued to express the SpaP/S1 fusion protein indicating the stability of the
      fusion gene in vivo. Secretory (S) IgA antibody against PT could be detected in
      saliva from RJM4-colonized mice but not from the control groups of mice. SIgA
      against SpaP was also detected in saliva from the RJM4-inoculated and the S.
      gordonii SL3 (control)-inoculated mice. Serum antibodies against PT and SpaP were
      not detected in these animals. In conclusion, long-term oral colonization of
      BALB/c mice with our recombinant S. gordonii was established and the colonization
      elicited mucosal antibodies against PT and SpaP.

PMID- 11959434
TI  - Isolation and characterization of dibenzofuran-degrading bacteria.
AB  - Two bacterial strains capable of utilizing dibenzofuran (DF) as a sole carbon
      source were isolated from soil samples of reclaimed land. The strains designated
      HL1 and HL7 were identified as Klebsiella sp. and Sphingomonas sp., respectively,
      on the basis of biochemical characteristics and the sequences of the 16S
      ribosomal DNA. Sphingomonas sp. strain HL7 degraded non-, mono- and also
      dichlorinated DF and dibenzo-p-dioxin (DD). Klebsiella sp. strain HL1 was able to
      degrade non- and monochlorinated DFs and DDs, but not dichlorinated ones. The
      metabolites formed from DF by strains HL1 and HL7 were similar to those by dioxin
      degrading bacteria Sphingomonas sp. strain RW1 except for salicylic acid and
      catechol. Strain HL7 had a gene homologous to that encoding the dioxin
      dioxygenase alpha-subunit (dxnA1) gene of Sphingomonas sp. strain RW1. However,
      Southern hybridization analysis showed that the size of an EcoRV-digested genomic
      fragment involving the dioxin dioxygenase gene of strain HL7 was smaller than
      that of strain RW1, and that strain HL1 did not have the homologous gene. Strains
      HL1 and HL7 provided useful information regarding the dioxygenase genes.

PMID- 11959435
TI  - Nucleotide structure of the Scytalidium hyalinum and Scytalidium dimidiatum 18S
      subunit ribosomal RNA gene: evidence for the insertion of a group IE intron in
      the rDNA gene of S. dimidiatum.
AB  - The molds Scytalidium dimidiatum (Nattrassia mangiferae synanamorph) and
      Scytalidium hyalinum are responsible for dermatomycosis in humans. We sequenced
      their 18S subunit ribosomal RNA gene to identify these species with molecular
      biology-based methods. The coding sequences differed by a single polymorphism (A
      in S. dimidiatum, G in S. hyalinum). Moreover, we found an insert at position
      1199 in the 18S rRNA gene sequence of S. dimidiatum. Its potential secondary
      structure was characteristic of a group IE intron. Bioinformatic and phylogenic
      group IE intron analyses generated four main homogeneous clusters. The S.
      dimidiatum intron is original and not related with other known IE group introns.

PMID- 11959436
TI  - Anaerobic C-ring cleavage of genistein and daidzein by Eubacterium ramulus.
AB  - Eubacterium ramulus, a flavonoid-degrading anaerobic bacterium from the human
      gastrointestinal tract, was tested for its ability to transform the isoflavonoids
      genistein-7-O-glucoside (genistin), genistein and daidzein. Genistein was
      completely degraded by E. ramulus via 6'-hydroxy-O-desmethylangolensin to 2-(4
      hydroxyphenyl)-propionic acid. Dihydrogenistein was neither observed as an
      intermediate in this transformation nor converted itself by growing cells or cell
      free extracts of E. ramulus. Genistein-7-O-glucoside was partially transformed by
      way of genistein to the product 2-(4-hydroxyphenyl)-propionic acid. Daidzein was
      in part degraded to O-desmethylangolensin, the corresponding metabolite to 6'
      hydroxy-O-desmethylangolensin. The hydroxyl group in position 6' of O
      desmethylangolensin is crucial for further degradation.

PMID- 11959437
TI  - The effect of antibiotic treatment on the intracellular nucleotide pools of
      Staphylococcus aureus.
AB  - In an assessment of antibiotic action on Staphylococcus aureus, we found that
      distinct changes in intracellular nucleotide pools occur depending on the
      antibiotic mode of action. In particular, we have quantitated the effect of
      antibiotics on pools of the nucleotide guanosine 3'-diphosphate, 5'-triphosphate
      (pppGpp). Intracellular pppGpp levels increased in response to treatment with the
      isoleucyl tRNA synthetase inhibitor mupirocin, the uncoupler carbonyl cyanide-m
      chlorophenylhydrazone, and rifampicin. These compounds were distinguishable by
      the degree in which they increased the pppGpp pool and by their differential
      effect on the pools of other nucleotides. This technique has been used to confirm
      and to refute the expected mode of action of several compounds identified as
      possible inhibitors of tRNA synthetases. Our results provide the framework for
      using nucleotide analysis in the assessment of novel antimicrobial compounds with
      unknown modes of action.

PMID- 11959438
TI  - ISMmy1, a novel insertion sequence of Mycoplasma mycoides subsp. mycoides small
      colony type.
AB  - A new insertion sequence, ISMmy1, has been identified in the bovine pathogen
      Mycoplasma mycoides subsp. mycoides biotype small colony (MmymySC). The
      occurrence of ISMmy1 in 15 MmymySC strains and 12 other mycoplasmas was examined
      by Southern blotting. All MmymySC strains showed identical hybridisation patterns
      except for the type strain PG1(T), the vaccine strain T1Sr49, and the strain
      Afade, which all had unique patterns. ISMmy1-like sequences were also found in
      the bovine pathogen Mycoplasma bovis strain Donetta(T) while mycoplasmas that are
      phylogenetically closer to MmymySC lack ISMmy1. This observation suggests
      horizontal transfer between MmymySC and M. bovis.

PMID- 11959439
TI  - Identification of a promoter for the crystal protein-encoding gene cry1Ia from
      Bacillus thuringiensis subsp. kurstaki.
AB  - Expression of cry1Ia, one of the insecticidal protein genes of Bacillus
      thuringiensis subsp. kurstaki, was studied at the transcriptional level. By
      primer extension analysis, we have identified for the first time, the
      transcription start point of cry1Ia. Upstream from the cry1Ia transcription start
      point, was found a nucleotide sequence partially homologous to the consensus
      sequence for the E sigma(E) holoenzyme of Bacillus subtilis. Thus, it was
      strongly suggested that the identified cry1Ia promoter was under the control of
      sigma(35), the B. thuringiensis homolog of sigma(E). The transcriptional activity
      from the promoter was detected only for the sporulating cells at T2 and T5
      stages.

PMID- 11959440
TI  - Transcriptional regulation of pseudobactin synthesis in the plant growth
      promoting Pseudomonas B10.
AB  - We have investigated the iron-dependent regulation of the psbA gene, encoding the
      enzyme L-ornithine N(5)-oxygenase in the rhizobacterium Pseudomonas B10. We have
      cloned and characterized a Pseudomonas B10 gene, designated psbS, required for
      psbA expression. PsbS is endowed with structural and functional features of
      extracytoplasmatic function (ECF) sigma factors, and is closely related to the
      iron starvation sigmas PvdS, PbrA, and PfrI, which mediate the iron-repressible
      expression of pseudobactin biosynthesis genes in different Pseudomonas species.
      Expression of psbA was found to be indirectly controlled by Fur, which abrogates
      psbS transcription in the presence of sufficient iron.

PMID- 11959441
TI  - Vacuolar H(+)-ATPase, but not mitochondrial F(1)F(0)-ATPase, is required for NaCl
      tolerance in Saccharomyces cerevisiae.
AB  - Salt tolerance in Saccharomyces cerevisiae is a complex trait, involving
      regulation of membrane polarization, Na(+) efflux and sequestration of Na(+) in
      the vacuole. Since transmembrane transport energized by H(+)-adenosine
      triphosphatases (ATPases) is common to all of these tolerance mechanisms, the
      objective of this study was to characterize the responses of the plasma membrane
      H(+)-ATPase, vacuolar H(+)-ATPase and mitochondrial F(1)F(0)-ATPase to NaCl
      stress. We hypothesized that since the vacuolar ATPase is responsible for
      generating the proton motive force required for import of cations (such as Na(+))
      into the vacuole, strains lacking this activity should be hypersensitive to NaCl.
      We found that strains lacking vacuolar ATPase activity were in fact
      hypersensitive to NaCl, while strains lacking ATP synthase were not. This effect
      was specific to the ionic component of NaCl stress, since the mutant strains were
      indistinguishable from wild-type and complemented strains in the presence of
      sorbitol.

PMID- 11959442
TI  - Mycosporine-2-glycine is the major mycosporine-like amino acid in a unicellular
      cyanobacterium (Euhalothece sp.) isolated from a gypsum crust in a hypersaline
      saltern pond.
AB  - Mycosporine-like amino acids (MAAs) were extracted from a unicellular
      cyanobacterium (Euhalothece sp.) isolated from a gypsum crust on the bottom of a
      hypersaline saltern pond in Eilat, Israel. When grown at high light intensities,
      this isolate contained high concentrations of two MAAs, one showing maximum
      optical density at 331 nm and one at 362 nm. The compound absorbing at 331 nm was
      purified by preparative high performance liquid chromatography, and its structure
      was elucidated by one-dimensional ((1)H and (13)C) and two-dimensional nuclear
      magnetic resonance, mass spectrometry and amino acid analysis, and identified as
      mycosporine-2-glycine. This is the first report of mycosporine-2-glycine in
      cyanobacteria.

PMID- 11959443
TI  - Isolation and characterization of a motile hydrogenotrophic methanogen from rice
      paddy field soil in Japan.
AB  - A hydrogenotrophic motile methanogen was isolated from flooded Japanese paddy
      field soil. Anaerobic incubation of the paddy soil on H(2)-CO(2) at 20 degrees C
      led to the enrichment of symmetrically curved motile autofluorescent rods. The
      methanogenic strain TM20-1 isolated from the culture was halotolerant and
      utilized H(2)-CO(2), 2-propanol-CO(2), or formate as a sole methanogenic
      substrate. Based on the 16S rRNA gene sequence similarity (94.8%) with
      Methanospirillum hungateii, and on the physiological and phenotypic
      characteristics, TM20-1 was suggested to be a newly identified species belonging
      to the genus Methanospirillum. This is the first report of isolation of the genus
      Methanospirillum strain from a rice paddy field.

PMID- 11959444
TI  - Identification of the cadBA operon from Vibrio vulnificus and its influence on
      survival to acid stress.
AB  - By a transposon-tagging method, cadBA genes encoding a lysine/cadaverin
      antiporter and a lysine decarboxylase were identified and cloned from Vibrio
      vulnificus. The deduced amino acid sequences of cadBA were 64-97% similar to
      those reported from other Enterobacteriaceae. Functions of cadBA genes on acid
      tolerance were assessed by comparing acid tolerances of V. vulnificus and its
      isogenic mutants, whose cadBA genes were separately inactivated by allelic
      exchanges. The results demonstrated that gene products of cadBA contribute to
      acid tolerance of V. vulnificus, and that their contribution is dependent on
      prior exposure of cells to moderately acidic pH.

PMID- 11959445
TI  - Aspergillus nidulans sod(VI)C1 mutation causes defects in cell wall biogenesis
      and protein secretion.
AB  - Growth at the restrictive temperature (42 degrees C) of Aspergillus nidulans
      B120, carrying the conditional-lethal mutation sod(VI)C1, was partially improved
      by the addition of 1.0 M sorbitol to the medium. The mutant grown at 42 degrees
      C, with osmotic stabilizer, showed abnormal hyphal morphology, a decrease in beta
      1,3-glucan synthase activity as well as cell wall sugar content, but an increase
      in chitin synthase activity and N-acetyl-glucosamine content. The mutation also
      affected the secretion of extracellular protease. The temperature-dependent osmo
      sensitive phenotype of a Saccharomyces cerevisiae alpha-COP mutation can be
      rescued by the A. nidulans sod(VI)C(+) gene. These results indicate that the
      sod(VI)C1 mutation affects proper processing of secretory proteins destined for
      the surface of cells or beyond.

PMID- 11959446
TI  - Colicins produced by the Escherichia fergusonii strains closely resemble colicins
      encoded by Escherichia coli.
AB  - Plasmid DNA of six Escherichia fergusonii colicinogenic strains (three producers
      of colicin E1, two of Ib and one of Ia) was isolated and the colicin-encoding
      regions of the corresponding Col plasmids were sequenced. Two new variants of
      colicin E1, one of colicin Ib, and one of colicin Ia were identified as well as
      new variants of the colicin E1 and colicin Ib immunity proteins and the colicin
      E1 lysis polypeptide. The recombinant Escherichia coli producer harboring pColE1
      from E. fergusonii strain EF36 (pColE1-EF36) was found to be only partially
      immune to E1 colicins produced by two other E. fergusonii strains suggesting that
      pColE1-EF36 may represent an ancestor ColE1 plasmid.

PMID- 11959447
TI  - Induction and repression of the sty operon in Pseudomonas putida CA-3 during
      growth on phenylacetic acid under organic and inorganic nutrient-limiting
      continuous culture conditions.
AB  - The effects of various nutrient-limiting conditions on expression of the sty
      operon in Pseudomonas putida CA-3 were investigated. It was observed that
      limiting concentrations of the carbon source phenylacetic acid, resulted in high
      levels of phenylacetyl coenzyme A (CoA) ligase activity, this was accompanied
      also by upper pathway styrene monooxygenase enzyme activity. The introduction of
      inorganic nutrient limitations, (nitrate, sulfate and phosphate), caused a
      dramatic reduction in detectable levels of phenylacetyl CoA ligase activity,
      particularly in the presence of the primary carbon source, succinate. Under these
      conditions it was no longer possible to detect styrene monooxygenase activity.
      Reverse transcription PCR analysis of total RNA, isolated under each of the
      continuous culture conditions examined, revealed that variations in the levels of
      enzyme activity coincided with altered patterns of corresponding paaK
      (phenylacetyl CoA ligase) and styA (styrene monooxygenase) gene expression.
      Transcription of the upper pathway regulatory sensor kinase gene styS was also
      observed to be growth condition-dependent. These observations suggest that
      induction/repression of the sty operon in P. putida CA-3, during growth on
      phenylacetic acid under continuous culture conditions, involves regulatory
      mechanisms coordinately affecting both the upper and lower pathways and acting at
      the level of gene transcription.

PMID- 11959448
TI  - Agaricus bisporus and Coprinus bilanatus TRP2 genes are tri-functional with
      conserved intron and domain organisations.
AB  - Cloned homobasidiomycete TRP2 genes for Agaricus bisporus and Coprinus bilanatus
      were sequence-characterised. Both genes encode tri-functional proteins with
      activity domains for glutamine amidotransferase (GAT; G domain), indole glycerol
      phosphate synthase (InGP; C domain) and phosphoribosyl anthranilate isomerase (F
      domain). A conserved intron disrupts the GAT-coding sequence in both genes.
      Consensus amino acid (aa) signatures were identified for GAT and InGP, but in the
      latter 15-aa signature, one residue did not fit the previously defined consensus.
      Protein architecture and parsimony analysis with analogous proteins indicate
      domain organisation (NH(2)-G-C-F-COOH) was as for other filamentous fungi. The
      data do not support earlier suggestions that the three activity domains are
      detached in A. bisporus.

PMID- 11959449
TI  - Active and energy-dependent rapid formation of cell aggregates in the
      thermophilic photosynthetic bacterium Chloroflexus aggregans.
AB  - The thermophilic filamentous phototroph Chloroflexus aggregans was able to form a
      bacterial mat-like dense cell aggregate rapidly. The aggregate formation, which
      was observed in growing cells in a liquid medium in a bottle, occurred every time
      within 20-30 min after the cells were dispersed by shaking. The aggregation
      depended on the energy supplied by photosynthesis or respiration. Cells
      aggregated most rapidly under temperature and pH conditions that support maximum
      growth. The aggregation was also accelerated by the addition of 3-isobutyl-1
      methylxanthine that inhibits cyclic 3',5'-AMP phosphodiesterase. Microscopic
      observation revealed that the bacterium has a fast gliding mobility (1-3 microm
      s(-1)). The distinctive cell aggregation of C. aggregans was due to this rapid
      gliding movement.

PMID- 11959450
TI  - Mycoplasma gallisepticum rpoA gene cluster.
AB  - Two conservative gene clusters, the S10 ribosomal protein region and one (of the
      two) set of rRNA genes, were split in a genome crossover rearrangement event in
      Mycoplasma gallisepticum. As a result of the rearrangement the major part of the
      S10 ribosomal protein cluster is located upstream of genes for 23S-5S rRNA (rrn23
      5), but the genes infA-rpl36-rps13-rpoA-rpl17 are located immediately downstream
      of the isolated gene for 16S rRNA (rrn16). A new ribosomal protein cluster infA
      rpl36-rps13-rpoA-rpl17-rps16-trmD-rpl19 was formed. Reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis revealed that this ribosomal protein
      cluster is an operon.

PMID- 11959451
TI  - Nitrogen assimilation in Corynebacterium diphtheriae: pathways and regulatory
      cascades.
AB  - Genes encoding proteins for ammonium uptake, assimilation, and the nitrogen
      regulatory system in Corynebacterium diphtheriae were studied on basis of
      homology searches using Corynebacterium glutamicum genes as query sequences.
      Regulation of transcription of these genes in response to nitrogen starvation was
      analyzed by RNA hybridization experiments and knock-out mutants were generated to
      verify the function of distinct genes. In this communication, we were able to
      identify the key components of ammonium assimilation pathways and nitrogen
      regulation in C. diphtheriae. Moreover, we show in this study that molecular
      biology methods and vectors developed for C. glutamicum can be applied in C.
      diphtheriae. The results obtained strengthens the role of C. glutamicum as a
      model organism for mycolic acids-containing actinomycetes.

PMID- 11959452
TI  - Inactivation of a Helicobacter pylori DNA methyltransferase alters dnaK operon
      expression following host-cell adherence.
AB  - The Helicobacter pylori hpyIM gene encodes a type II DNA methyltransferase that
      is highly conserved among strains. To investigate the potential role of M.HpyI
      methyltransferase activity in controlling gene expression in H. pylori, we
      analyzed gene transcription profiles in wild-type strain J166 and an isogenic
      hpyIM mutant strain using gene arrays. This analysis showed that the expression
      of a majority of genes was unaffected by hpyIM mutation, especially in
      exponential phase cultures. However, in stationary phase cultures and in cells
      adherent to AGS gastric epithelial cells in vitro, loss of hpyIM function altered
      the expression of the stress-responsive dnaK operon. Complementation of the hpyIM
      mutation using a shuttle plasmid encoding a wild-type copy of the gene re
      established the wild-type pattern of dnaK operon expression. These data suggested
      that hpyIM, encoding a DNA methyltransferase, may have a role in H. pylori
      physiology that supersedes its original function in a type II restriction
      modification system.

PMID- 11959455
TI  - Genetic defects in hepatobiliary transport.
AB  - Bile formation, the exocrine function of the liver, represents a process that is
      unique to the hepatocyte as a polarized epithelial cell. The generation of bile
      flow is an osmotic process and largely depends on solute secretion by primary
      active transporters in the apical membrane of the hepatocyte. In recent years an
      impressive progress has been made in the discovery of these proteins, most of
      which belong to the family of ABC transporters. The number of identified ABC
      transporter genes has been exponentially increasing and the mammalian subfamily
      now counts at least 52. This development has been of crucial importance for the
      elucidation of the mechanism of bile formation, and it is therefore not
      surprising that the development in this field has run in parallel with the
      discovery of the ABC genes. With the identification of these transporter genes,
      the background of a number of inherited diseases, which are caused by mutations
      in these solute pumps, has now been elucidated. We now know that at least six
      primary active transporters are involved in canalicular secretion of biliary
      components (MDR1, MDR3, BSEP, MRP2, BCRP and FIC1). Four of these transporter
      genes are associated with inherited diseases. In this minireview we will shortly
      describe our present understanding of bile formation and the associated inherited
      defects.

PMID- 11959456
TI  - Events upstream of mitochondrial protein import limit the oxidative capacity of
      fibroblasts in multiple mitochondrial disease.
AB  - To investigate whether protein import is defective in mitochondrial disease, we
      compared the rate of import and the expression of protein import machinery
      components in skin fibroblasts from control subjects and a patient with multiple
      mitochondrial disease (MMD). The patient exhibited a 35% decrease in cytochrome c
      oxidase activity and a 59% decrease in cellular oxygen consumption compared to
      control. Western blot analyses revealed that patient levels of MDH, mtHSP70,
      HSP60, and Tom20 protein were 57%, 20%, 75% and 100% of control cells,
      respectively. MDH and Tom20 mRNA levels were not different from control levels,
      whereas mtHSP70 mRNA were 50% greater than control. Radiolabeled MDH was imported
      into mitochondria with equal efficiency between patient (44% of total
      synthesized) and control (43%) cells, although the total MDH synthesized in
      patient cells was reduced by about 40%. The unaffected levels of mRNA and post
      translational import into mitochondria, combined with reduced protein levels of
      MDH, mtHSP70, and HSP60 suggest a translational defect in this patient with MMD.
      This was verified by the 50% reduction in overall cellular protein synthesis in
      the patient compared to control. Further, the similar import rates between
      patient and control cells suggest an important role for Tom20, but a lesser role
      for mtHSP70 in regulating protein import into mitochondria.

PMID- 11959457
TI  - Effects of aluminum and zinc on the oxidative stress caused by 6-hydroxydopamine
      autoxidation: relevance for the pathogenesis of Parkinson's disease.
AB  - Aluminum and zinc have been related to the pathogenesis of Parkinson's disease
      (PD), the former for its neurotoxicity and the latter for its apparent
      antioxidant properties. 6-Hydroxydopamine (6-OHDA) is an important neurotoxin
      putatively involved in the pathogenesis of PD, its neurotoxicity often being
      related to oxidative stress. The potential effect of these metals on the
      oxidative stress induced by 6-OHDA autoxidation and the potential of ascorbic
      acid (AA), cysteine, and glutathione to modify this effect were investigated.
      Both metals, particularly Al3+, induced a significant reduction in *OH production
      by 6-OHDA autoxidation. The combined action of AA and a metal caused a
      significant and sustained increase in *OH generation, particularly with Al3+,
      while the effect of sulfhydryl reductants was limited to only the first few
      minutes of the reaction. However, both Al3+ and Zn2+ provoked a decrease in the
      lipid peroxidation induced by 6-OHDA autoxidation using mitochondrial
      preparations from rat brain, assessed by TBARS formation. In the presence of AA,
      only Al3+ induced a significant reduction in lipid peroxidation. After
      intrastriatal injections of 6-OHDA in rats, tyrosine hydroxylase
      immunohistochemistry revealed that Al3+ reduces 6-OHDA-induced dopaminergic
      lesion in the striatum, which corroborates the involvement of lipid peroxidation
      in 6-OHDA neurotoxicity and appears to discard the participation of this
      mechanism on PD by Al3+ accumulation. The previously reported antioxidant
      properties of Zn2+ appear to be related to the induction of Zn2+-containing
      proteins and not to the metal per se.

PMID- 11959458
TI  - alpha-Mannosidosis in the guinea pig: cloning of the lysosomal alpha-mannosidase
      cDNA and identification of a missense mutation causing alpha-mannosidosis.
AB  - alpha-Mannosidosis is a lysosomal storage disorder caused by deficient activity
      of the lysosomal alpha-mannosidase. We report here the sequencing and expression
      of the lysosomal alpha-mannosidase cDNA from normal and alpha-mannosidosis guinea
      pigs. The amino acid sequence of the guinea pig enzyme displayed 82-85% identity
      to the lysosomal alpha-mannosidase in other mammals. The cDNA of the alpha
      mannosidosis guinea pig contained a missense mutation, 679C>T, leading to
      substitution of arginine by tryptophan at amino acid position 227 (R227W). The
      R227W allele segregated with the alpha-mannosidosis genotype in the guinea pig
      colony and introduction of R227W into the wild-type sequence eliminated the
      production of recombinant alpha-mannosidase activity in heterologous expression
      studies. Furthermore, the guinea pig mutation has been found in human patients.
      Our results strongly indicate that the 679C>T mutation causes alpha-mannosidosis
      and suggest that the guinea pig will be an excellent model for investigation of
      pathogenesis and evaluation of therapeutic strategies for human alpha
      mannosidosis.

PMID- 11959459
TI  - Oxidative stress increases internal calcium stores and reduces a key
      mitochondrial enzyme.
AB  - Fibroblasts from patients with genetic and non-genetic forms of Alzheimer's
      disease (AD) show many abnormalities including increased bombesin-releasable
      calcium stores (BRCS), diminished activities of the mitochondrial alpha
      ketoglutarate dehydrogenase complex (KGDHC), and an altered ability to handle
      oxidative stress. The link between genetic mutations (and the unknown primary
      event in non-genetic forms) and these other cellular abnormalities is unknown. To
      determine whether oxidative stress could be a convergence point that produces the
      other AD-related changes, these experiments tested in fibroblasts the effects of
      H(2)O(2), in the presence or absence of select antioxidants, on BRCS and KGDHC.
      H(2)O(2) concentrations that elevated carboxy-dichlorofluorescein (c-H(2)DCF)
      detectable ROS increased BRCS and decreased KGDHC activity. These changes are in
      the same direction as those in fibroblasts from AD patients. Acute treatments
      with the antioxidants Trolox, or DMSO decreased c-H(2)DCF-detectable ROS by about
      90%, but exaggerated the H(2)O(2)-induced increases in BRCS by about 4-fold and
      did not alter the reduction in KGDHC. Chronic pretreatments with Trolox more than
      doubled the BRCS, tripled KGDHC activities, and reduced the effects of H(2)O(2).
      Pretreatment with DMSO or N-acetyl cysteine diminished the BRCS and either had no
      effect, or exaggerated the H(2)O(2)-induced changes in these variables. The
      results demonstrate that BRCS and KGDHC are more sensitive to H(2)O(2) derived
      species than c-H(2)DCF, and that oxidized derivatives of the antioxidants
      exaggerate the actions of H(2)O(2). The findings support the hypothesis that
      select abnormalities in oxidative processes are a critical part of a cascade that
      leads to the cellular abnormalities in cells from AD patients.

PMID- 11959460
TI  - Role of glycine-33 and methionine-35 in Alzheimer's amyloid beta-peptide 1-42
      associated oxidative stress and neurotoxicity.
AB  - Recent theoretical calculations predicted that Gly33 of one molecule of amyloid
      beta-peptide (1-42) (Abeta(1-42)) is attacked by a putative sulfur-based free
      radical of methionine residue 35 of an adjacent peptide. This would lead to a
      carbon-centered free radical on Gly33 that would immediately bind oxygen to form
      a peroxyl free radical. Such peroxyl free radicals could contribute to the
      reported Abeta(1-42)-induced lipid peroxidation, protein oxidation, and
      neurotoxicity, all of which are prevented by the chain-breaking antioxidant
      vitamin E. In the theoretical calculations, it was shown that no other amino
      acid, only Gly, could undergo such a reaction. To test this prediction we studied
      the effects of substitution of Gly33 of Abeta(1-42) on protein oxidation and
      neurotoxicity of hippocampal neurons and free radical formation in synaptosomes
      and in solution. Gly33 of Abeta(1-42) was substituted by Val (Abeta(1-42G33V)).
      The substituted peptide showed almost no neuronal toxicity compared to the native
      Abeta(1-42) as well as significantly lowered levels of oxidized proteins. In
      addition, synaptosomes subjected to Abeta(1-42G33V) showed considerably lower
      dichlorofluorescein-dependent fluorescence - a measure of reactive oxygen species
      (ROS) - in comparison to native Abeta(1-42) treatment. The ability of the
      peptides to generate ROS was also evaluated by electron paramagnetic resonance
      (EPR) spin trapping methods using the ultrapure spin trap N-tert-butyl-alpha
      phenylnitrone (PBN). While Abeta(1-42) gave a strong mixture of four- and six
      line PBN-derived spectra, the intensity of the EPR signal generated by Abeta(1
      42G33V) was far less. Finally, the ability of the peptides to form fibrils was
      evaluated by electron microscopy. Abeta(1-42G33V) does not form fibrils nearly as
      well as Abeta(1-42) after 48 h of incubation. The results suggest that Gly33 may
      be a possible site of free radical propagation processes that are initiated on
      Met35 of Abeta(1-42) and that contribute to the peptide's toxicity in Alzheimer's
      disease brain.

PMID- 11959461
TI  - FAD-linked mutations in presenilin 1 alter the length of Abeta peptides derived
      from betaAPP transmembrane domain mutants.
AB  - gamma-Secretase is an enzymatic activity responsible for the final cleavage of
      the amyloid precursor protein leading to the production of the amyloid beta
      peptide (Abeta). gamma-Secretase is likely an aspartyl protease, since its
      activity can be inhibited by both pepstatin and active-site directed aspartyl
      protease inhibitors. Recent work has indicated that presenilins 1 and 2 may
      actually be the gamma-secretase enzymes. Presenilin (PS) mutations, which lead to
      an increase in the production of a longer form of Abeta, are also the most common
      cause of familial Alzheimer's disease (FAD). Therefore, in an attempt to better
      characterize the substrate preferences of gamma-secretase, we performed
      experiments to determine how FAD-linked mutations in PS1 would affect the
      generation of Abeta peptides from full length precursor substrates that we have
      previously demonstrated to be proteolytically cleaved at alternative sites and/or
      by enzymatic activities that are pharmacologically distinct. Presenilin mutations
      increased the production of Abeta peptides from sites distal to the primary
      cleavage site ('longer' peptides) and in several cases also decreased production
      of 'shorter' peptides. These results support a model in which the FAD-linked
      mutants subtly alter the conformation of the gamma-secretase complex to favor the
      production of long Abeta.

PMID- 11959462
TI  - Magnetic investigations of human mesencephalic neuromelanin.
AB  - Pigmentation of neurons in substantia nigra is due to neuromelanin, a pigment
      that stores large amounts of iron. Human mesencephalic neuromelanin has been
      investigated by means of magnetic susceptibility measurements as a function of
      temperature. Magnetic measurements provide a physico-chemical characterization of
      the iron cluster buried in the organic melanin matrix and support the view that
      iron is not simply chelated, but rather is organized in a three-dimensional
      network. The paramagnetism of isolated iron ions is observed, in agreement with
      electron paramagnetic resonance spectroscopy. Furthermore, antiferromagnetic
      grains with a large size distribution function are present. These grains contain
      N spins coupled antiferromagnetically; however, N(1/2) spins are decoupled from
      the grain bulk and parallelly aligned. The latter subgrains are superparamagnetic
      with a blocking temperature ranging between 5 K and room temperature. This
      behavior has not been observed in synthetic melanin, where the paramagnetic
      contribution is strongly enhanced. Preliminary results on pigment isolated from
      patients affected by Parkinson's disease, a neurodegenerative pathology involving
      primarily pigmented neurons in substantia nigra pars compacta, show a lower total
      magnetization compared to control neuromelanin. The temperature behavior of zero
      field cooling and field cooling magnetizations is similar for both. The
      significant depletion of iron content in Parkinson's disease neuromelanin could
      indicate a progressive Fe migration from its storage environment to the cytosol.

PMID- 11959463
TI  - Lactate accumulation rather than ATP depletion predicts ischemic myocardial
      necrosis: implications for the development of lethal myocardial injury.
AB  - In ischemia, the myocardial metabolic status determines the expansion of
      necrosis. Decreased ATP levels and increased lactate contents in ischemic
      myocardium undergoing lethal injury are known to be related to the expansion of
      irreversible damage. However, their individual contributions have not yet been
      firmly established. Using two differently effective protocols of ischemic
      preconditioning (IP short and IP long), ischemic cardioplegic arrest (CP) and
      their combination (IP+CP) to directly influence the metabolic status of porcine
      myocardium, graded preservations in ATP content and decreases in lactate
      accumulation during 45 min ischemia could be achieved (control: ATP, 0.15+/-0.03;
      lactate, 60.53+/-4.89 micromol/g wet weight; IP short, 0.33+/-0.10/27.42+/-3.90;
      IP long, 0.60+/-0.10/17.49+/-2.14; CP, 0.98+/-0.12/11.82+/-0.96; IP+CP, 2.24+/
      0.28/10.88+/-0.89; all P<0.001 vs. control). At the same time, a graded reduction
      of myocardial necrosis was observed (90.0+/-3.1 vs. 31.7+/-4.55 vs. 5.05+/-2.1
      vs. 0.0 [isolated patchy necroses] vs. none). Regression analysis revealed only a
      weak correlation of infarct size and ATP preservation (r=0.567). In fact, there
      was a biphasic relation: with ATP levels above 1 micromol/g wet weight, no
      infarction occurred. ATP levels below this threshold value were associated with
      steep increase in infarct size. However, even for this latter range, the
      regression coefficient remained low (r=0.654). Instead, over the entire range,
      there was a close, rectilinear correlation of infarct size and lactate
      accumulation (r=0.939). These data indicate that lactate accumulation rather than
      ATP depletion determines the development of lethal myocardial injury. However,
      the biphasic relation between ATP depletion and infarct size suggests the latter
      to play a permissive role, since above a threshold value of 1 micromol/g wet
      weight neither substantial lactate accumulation nor infarction was observed.
      Below this threshold, however, infarct size increased as lactate accumulated.

PMID- 11959464
TI  - Mediated biosensors.
AB  - Direct electrode transfer between enzyme and the electrode in biosensors requires
      high efficiency therefore, synthetic replacement for oxygen led to the
      development of enzyme mediators and modified electrodes in biosensor fabrication.
      In this context, a number of electron acceptors and complexes have been used.
      Present paper gives an overview of various methodologies involved in the mediated
      systems, their merits and wide applications.

PMID- 11959465
TI  - Reusable sensors in intrapartum foetal reflection pulse oximetry.
AB  - OBJECTIVES: To evaluate the accuracy of intrapartum foetal pulse oximetry
      (SO(2POX)) using reusable sensors and the effect of a sensor performance test on
      data quality. Furthermore, to assess the sensor-related costs by using reusable
      sensors and sensor performance test. METHODS: 36 reusable sensors were used for
      SO(2POX) during labour of 289 term foetuses. A sensor performance test device
      assessing the emitter and receiver capability and the firmness of attachment of
      the sensors had been developed and used in the last 134 measurements before each
      resterilisation. Oxygen saturation (SaO(2)) at birth was measured
      spectrophotometrically after cord blood sampling. The accuracy of SO(2POX) was
      evaluated by analysing its relationship to SaO(2). The valid SO(2POX) data, as
      confirmed by subsequent sensor test in the second group, was considered
      comparable with those with single sensor use. Sensor-related average cost
      (sensors, test device and sterilisation) of such measurements was compared with
      that of single sensor use. RESULTS: Eight sensors failed performance test despite
      valid pulse oximetry signal output during their last measurements. There were
      significant overall linear correlations between SO(2POX) and SaO(2) (r=0.45,
      P<0.0001). Separate analyses of regression in the group without sensor
      performance testing showed an r(2) of 0.41, whereas in the group with subsequent
      sensor performance testing, the r(2) was 0.52 (P<0.05). By reusing the sensors,
      the sensor-related cost per valid measurement was $18.9 and 71% lower compared to
      single use of sensors ($65). CONCLUSIONS: Pulse oximetry may reflect fetal oxygen
      saturation. Data quality may be compromised by insufficient sensor performance,
      even though the reflection signal quality is acceptable. If sensor performance is
      tested before each measurement, reusable sensors may reduce the costs of fetal
      pulse oximetry.

PMID- 11959466
TI  - Interaction of monosulfonate tetraphenyl porphyrin, a competitive inhibitor, with
      acetylcholinesterase.
AB  - Monosulfonate tetraphenyl porphyrin (TPPS(1)) forms a 1:1 complex with electric
      eel acetylcholinesterase (AChE) inducing a loss in TPPS(1) absorbance at 402 nm
      and the appearance of a new absorbance centered at 442 nm. In the presence of
      AChE, the fluorescence of TPPS(1) at 652 nm is slightly narrowed, with the
      maximal 652 nm fluorescence shifted from 407 to 412 nm excitation wavelength. The
      fluorescence peak of TPPS(1) at 712 nm shifts to 716 nm in the presence of AChE.
      TPPS(1) is a competitive inhibitor of AChE. The addition of acetylcholine iodide
      (AChI) or the competitive inhibitor tetracaine to the preformed AChE-TPPS(1)
      complex results in a loss of the 442 nm absorbance band as the porphyrin is
      displaced from AChE. The absorbance peak does not decrease in the presence of
      procaine, a non-competitive inhibitor.

PMID- 11959467
TI  - Gas phase activity of anti-FITC antibodies immobilized on a surface acoustic wave
      resonator device.
AB  - In this paper we present the results of a series of experiments on the activity
      of antibodies in a vapor phase sensor. For these experiments the sensor component
      was a ST-Quartz resonator with a center frequency of approximately 250 MHz. Anti
      FITC antibodies were attached to the electrodes on the device surface via a
      protein-A crosslinker. Surface acoustic wave (SAW) resonator devices with various
      coatings were mounted in TO-8 packages, inserted into our sensor head module and
      subjected to various fluorescent analyte gases. Numerous controls were performed
      including the use of coated and uncoated devices along with devices coated with
      antibodies which were not specific for the target analyte. The SAW immunosensor
      response was monitored and a baseline frequency shift was observed when the
      analyte being presented was the antigen for the immobilized antibody. To provide
      an independent measure of antibody/antigen binding, the devices were removed from
      the sensor head, washed with a buffer solution to remove any unbound analyte, and
      then inspected using a confocal laser scanning microscope (CLSM). Since all the
      analytes being used in these experiments were fluorescent this afforded us the
      opportunity to visualize the attachment of the analyte to the antibody film.
      Given the high resolution of the CLSM, we were able to identify the location of
      the attachment of the fluorescent analytes relative to the 1.5 microm wide
      electrodes of the SAW device. We believe that these experiments demonstrate that
      we have achieved real time molecular recognition of these small molecules in the
      vapor phase.

PMID- 11959468
TI  - Ion-exchange voltammetry and electrocatalytic sensing capabilities of cytochrome
      c at polyestersulfonated ionomer coated glassy carbon electrodes.
AB  - The incorporation and electrochemical behaviour of cytochrome c (Cyt C) at glassy
      carbon electrodes modified with the polyestersulfonated ionomer Eastman AQ 55 are
      examined. The presence of the polyelectrolytic coating allows the
      preconcentration of the protein within the polymer and the observation of the
      direct electrochemistry of Cyt C at the modified electrode without addition of
      promoters or mediators in the solutions. The dependence of voltammetric signals
      on typical parameters such as solution pH and nature or concentration of the
      supporting electrolyte supports the ion-exchange nature of the incorporation
      process. The relevant role of the permselectivity of the polymeric modifier is
      highlighted also by the study of electrocatalytic processes which take place at
      the modified electrode loaded with Cyt C. No electrocatalytic effect is observed
      when the electrogenerated dication (ferricenylmethyl)trimethylammonium is present
      as possible oxidant. On the contrary, electrocatalytic current enhancements are
      observed for anionic substrates such as Fe(CN)(6)(3-) (oxidant) and ascorbate
      (reductant). Catalytic currents increase with the substrate concentration, with
      higher sensitivity for Fe(CN)(6)(3-). Due to ionic repulsion, the reaction with
      anions occurs at the polymer-solution interface. In the case of chemically
      unstable substrates, such as superoxide anion, ionic repulsion slow down the
      approach rate of the substrate so that spontaneous decomposition can prevail over
      the reaction with Cyt C incorporated in the coating.

PMID- 11959469
TI  - Voltage-induced inhibition of antigen-antibody binding at conducting optical
      waveguides.
AB  - Optical waveguides coated with electrically conducting indium-tin oxide (ITO) are
      demonstrated here as a new class of substrate for fluorescent immunosensors.
      These waveguides combine electrochemical control with evanescent excitation and
      image-based detection. Presented here are preliminary results utilizing these
      waveguides that demonstrate influence of waveguide voltage on antigen binding.
      Specifically, waveguide surfaces were bisected into electrically addressable
      halves, anti-ovalbumin immobilized in patterns on their surfaces, and a 1.3 V
      bias applied between waveguide halves in the presence of Cy5-labeled ovalbumin in
      10 mM phosphate buffer (pH 7.4) containing 150 mM NaCl and 0.05% Tween-20.
      Fluorescence imaging indicated that binding of the antigen to positively biased
      waveguide halves was inhibited nearly 10-fold compared with negatively biased
      waveguide halves and unbiased controls. Furthermore, it is shown that ovalbumin
      binding to positively biased waveguide regions is regenerated after removal of
      applied voltage. These results suggest that electrochemical control of
      immunosensor substrates can be used as a possible strategy toward minimizing
      cross-reactive binding and/or nonspecific adsorption, immunosensor regeneration,
      and controlled binding.

PMID- 11959470
TI  - On-line microbial biosensing and fingerprinting of water pollutants.
AB  - The potential for biosensors to contribute to on-line toxicity testing for
      monitoring of water quality is currently constrained both by the relevance of the
      biosensors available and the technology for biosensor delivery. This paper
      reports the use of novel slow release biosensor delivery for on-line monitoring
      instrumentation, with environmentally relevant bacteria for both simple toxicity
      testing and more complex toxicity fingerprinting of industrial effluents. The on
      line toxicity test, using bioluminescence-based biosensors, proved to be as
      sensitive and reliable as the corresponding batch test, with comparable
      contaminant EC(50) values from both methods. Toxicity fingerprinting through the
      investigation of the kinetics (dose-response) and the dynamics (response with
      time) of the biosensor test response proved to be diagnostic of both effluent
      type and composition. Furthermore, the slow release of biosensors immobilised in
      a polyvinyl alcohol (PVA) matrix greatly improved biosensor delivery, did not
      affect the sensitivity of toxicity testing, and demonstrated great potential for
      inclusion in on-line monitoring instrumentation.

PMID- 11959471
TI  - Enhancement of operational stability of an enzyme biosensor for glucose and
      sucrose using protein based stabilizing agents.
AB  - With the incorporation of lysozyme during the immobilization step, considerable
      enhancement of the operational stability of a biosensor has been demonstrated in
      the case of an immobilized single enzyme (glucose oxidase) system for glucose and
      multienzyme (invertase, mutarotase and glucose oxidase) system for sucrose. Thus
      an increased number of repeated analyses of 750 samples during 230 days for
      glucose and 400 samples during 40 days of operation for sucrose have been
      achieved. The increased operational stability of immobilized single and
      multienzyme system, will improve the operating cost effectiveness of the
      biosensor.

PMID- 11959472
TI  - Transient absorption and photovoltage study of' self-assembled
      bacteriorhodopsin/polycation multilayer films.
AB  - A series of organized (PDAC/PM)(n) (poly(diallyldimethylammonium chloride)/purple
      membrane) multilayer films were prepared by alternate adsorptions of positively
      charged PDAC polyelectrolyte and negatively charged purple membrane (PM). The
      kinetics of the photocycle of bacteriorhodopsin (bR) in PM was studied by flash
      photolysis and transient photovoltage methods. Although the orientation of the
      adsorbed bR depends on the pH of the PM suspension, the kinetics of the photo
      induced reaction cycle in dehydrated films is independent of the deposition pH.
      In dry (PDAC/PM)(n) films the decay of the M intermediate to the initial bR state
      is multiexponential and delayed to several minutes for both orientations. A
      simultaneous two-exponential decay in millisecond time domain was observed at red
      wavelengths. The source of the red-shifted absorption is suggested to be the
      C(610) intermediate of the cis photocycle of bR.

PMID- 11959474
TI  - Determination of ivermectin in bovine liver by optical immunobiosensor.
AB  - A rapid and sensitive biosensor immunoassay was developed for residues of the
      antiparasitic agent ivermectin in bovine liver. A detection limit of 19.1 ng g(
      1) was achieved. The sensor employed was a Biacore optical instrument based on
      surface plasmon resonance. 5-O-succinoylivermectin-apo-transferrin conjugate was
      used to produce monoclonal antibody while a second derivative, ivermectin-oxime,
      was immobilised onto the surface of a sensor chip. A range of assay parameters
      (flow rate, injection time, temperature) and extraction techniques were
      investigated. In the final assay procedure, ivermectin was extracted with
      acetonitrile followed by C(8) SPE clean-up. Matrix effect was minimised by
      increasing the flow rate to 25 microl min(-1) and reducing the sample injection
      time to 2 min. The average value for liver samples spiked at 100 ng g(-1) (the
      MRL for the drug) and 50 ng g(-1) concentrations were 93.7 and 43.2 ng g(-1),
      respectively.

PMID- 11959473
TI  - A new amperometric enzyme electrode for alcohol determination.
AB  - A new enzyme electrode for the determination of alcohols was developed by
      immobilizing alcohol oxidase in polvinylferrocenium matrix coated on a Pt
      electrode surface. The amperometric response due to the electrooxidation of
      enzymatically generated H(2)O(2) was measured at a constant potential of +0.70 V
      versus SCE. The effects of substrate, buffer and enzyme concentrations, pH and
      temperature on the response of the electrode were investigated. The optimum pH
      was found to be pH 8.0 at 30 degrees C. The steady-state current of this enzyme
      electrode was reproducible within +/-5.0% of the relative error. The sensitivity
      of the enzyme electrode decreased in the following order: methanol>ethanol>n
      butanol>benzyl alcohol. The linear response was observed up to 3.7 mM for
      methanol, 3.0 mM for ethanol, 6.2 mM for n-butanol, and 5.2 mM for benzyl
      alcohol. The apparent Michaelis-Menten constant (K(Mapp)) value and the
      activation energy, E(a), of this immobilized enzyme system were found to be 5.78
      mM and 38.07 kJ/mol for methanol, respectively.

PMID- 11959475
TI  - Construction of an acetylcholinesterase-choline oxidase biosensor for aldicarb
      determination.
AB  - In this study, acetylcholinesterase and choline oxidase were co-immobilized on
      poly(2-hydroxyethyl methacrylate) membranes and the change in oxygen consumption
      upon aldicarb introduction was measured. Immobilization of the enzymes was
      achieved either by entrapment or by surface attachment via a hybrid
      immobilization method including epichlorohydrin and Cibacron Blue F36A
      activation. Immobilized enzymes had a long-storage stability (only 15% activity
      decrease in 2 months in wet storage and no activity loss in dry storage).
      Aldicarb detection studies showed that a linear working range of 10-500 and 10
      250 ppb aldicarb could be achieved by entrapped and surface immobilized enzymes,
      respectively. Enzymes immobilized on membrane surfaces responded to aldicarb
      presence more quickly than entrapped enzymes. Aldicarb concentrations as low as
      23 and 12 ppb could be detected by entrapped and surface immobilized enzymes,
      respectively, in 25 min.

PMID- 11959476
TI  - A glucose biosensor based on microporous polyacrylonitrile synthesized by single
      rare-earth catalyst.
AB  - A glucose biosensor was constructed by electrochemical adsorption of glucose
      oxidase (GOD) in microporous polyacrylonitrile (PAN), which was synthesized by
      single rare-earth catalyst-Y(OAr)(3.) The biosensor shows a fast response, good
      operational stability and reproducibility. The influences of molecular weight of
      polymer, pH, operating potential and temperature on the biosensor response were
      explored by amperometric method. The apparent activation energy and optimum pH of
      enzyme-catalyzed reaction are 35.9 kJ mol(-1) and 6.2, respectively.

PMID- 11959477
TI  - An AFM determination of the effects on surface roughness caused by cleaning of
      fused silica and glass substrates in the process of optical biosensor
      preparation.
AB  - The covalent attachment of organic films and of biological molecules to fused
      silica and glass substrates is important for many applications. For applications
      such as biosensor development, it is desired that the immobilised molecules be
      assembled in a uniform layer on the surface so as to provide for reproducibility
      and speed of surface interactions. For optimal derivatisation the surface must be
      appropriately cleaned to remove contamination, to create surface attachment sites
      such as hydroxyl groups, and to control surface roughness. The irregularity of
      the surface can be significant in defining the integrity and density of
      immobilised films. Numerous cleaning methods exist for fused silica and glass
      substrates and these include gas plasmas, and combinations of acids, bases and
      organic solvents that are allowed to react at varying temperatures. For many
      years, we have used a well established method based on a combination of washing
      with basic peroxide followed by acidic peroxide to clean and hydroxylate the
      surface of fused silica and glass substrates before oligonucleotide
      immobilisation. Atomic force microscopy (AFM) has been used to evaluate the
      effect of cleaning on surface roughness for various fused silica and glass
      samples. The results indicate that surface roughness remains substantial after
      use of this common cleaning routine, and can provide a surface area that is more
      than 10% but less than 30% larger than anticipated from geometric considerations
      of a planar surface.

PMID- 11959478
TI  - Manometric biosensor for on-line measurement of milk urea.
AB  - Performance of a prototype sensor for on-line measurement of urea in milk during
      milking was evaluated. The sensor was based on a manometric assay of the carbon
      dioxide generated by the enzymatic hydrolysis of urea. Temperature compensation
      of the sensor was described briefly, and was shown to be effective. The
      calibration of the sensor was described and resulted in a standard calibration
      error of about 0.15 mM of urea. The standard error of the sensor in milk was
      shown to be about 0.25 mM (given a physiological range of about 2-7 mM in cow
      milk). The sensor was simple, inexpensive, suffered from no interferences in raw
      milk, and completed a measurement cycle in about 5 min (less than the time to
      milk a typical cow). A custom made sampling device, whereby milk was passively
      collected from the milk line under vacuum, was shown to collect an ample volume
      within 10 s to run a test with the sensor. No measurable bubbles or foam were
      introduced from the sampling mechanism so that the milk sampled was not
      diminished in density compared to samples taken by other methods.

PMID- 11959479
TI  - Stabilized lipid film based biosensor for atenolol.
AB  - This work reports a technique for the stabilization after storage in air of a
      lipid film based biosensor for atenolol. Microporous filters composed of glass
      fibers (nominal pore sizes 0.7 and 1.0 microm) were used as supports for the
      formation and stabilization of these devices. The lipid film is formed on the
      filter by polymerization prior to its use. Methacrylic acid was the functional
      monomer, ethylene glycol dimethacrylate was the crosslinker and 2,2'-azobis-(2
      methylpropionitrile) was the initiator. The method for preparation of stabilized
      lipid film biosensor is studied throughout this work. The response towards
      atenolol of these stabilized lipid membrane biosensor, for repetitive use,
      composed of phosphatidylcholine was compared with planar freely suspended bilayer
      lipid membranes (BLMs). The stabilized lipid membranes provided similar
      artificial ion gating events as BLMs in the form of transient signals and can
      function for repetitive uses after storage in air. This will allow the practical
      use of the techniques for chemical sensing based on lipid films and
      commercialization of these devices.

PMID- 11959480
TI  - Detection of Staphylococcus aureus enterotoxin B at femtomolar levels with a
      miniature integrated two-channel surface plasmon resonance (SPR) sensor.
AB  - Surface plasmon resonance (SPR) biosensors offer the capability for continuous
      real-time monitoring. The commercial instruments available have been large in
      size, expensive, and not amenable to field applications. We report here an SPR
      sensor system based on a prototype two-channel system similar to the single
      channel Spreeta devices. This system is an ideal candidate for field use. The two
      channel design provides a reference channel to compensate for bulk refractive
      index (RI), non-specific binding and temperature variations. The SPR software
      includes a calibration function that normalizes the response from both channels,
      thus enabling accurate referencing. In addition, a temperature-controlled
      enclosure utilizing a thermo-electric module based on the Peltier effect provides
      the temperature stability necessary for accurate measurements of RI. The complete
      SPR sensor system can be powered by a 12V battery. Pre-functionalized,
      disposable, gold-coated thin glass slides provide easily renewable sensor
      elements for the system. Staphylococcus aureus enterotoxin B (SEB), a small
      protein toxin was directly detectable at sub-nanomolar levels and with
      amplification at femtomolar levels. A regeneration procedure for the sensor
      surface allowed for over 60 direct detection cycles in a 1-month period.

PMID- 11959481
TI  - Plant tissue-based chemiluminescence flow biosensor for determination of unbound
      dopamine in rabbit blood with on-line microdialysis sampling.
AB  - A novel plant tissue-based chemiluminescence (CL) biosensor for dopamine combined
      with flow injection analysis is presented in this paper. The potato roots act as
      molecular recognition elements. Dopamine is oxidized by oxygen under the
      catalysis of polyphenol oxidase in the tissue column to produce hydrogen
      peroxide, which can react with luminol in the presence of peroxidase of potato
      tissue to generate CL signal. The CL emission intensity was linear with dopamine
      concentration in the range of 1x10(-5)-1x10(-7) g/ml and the detection limit was
      5.3x10(-8) g/ml (3sigma) with a relative standard deviation of 1.7%. Combined
      with microdialysis sampling, the biosensor was applied to monitor the variation
      of dopamine level in the blood of rabbit after the administration of dopamine to
      demonstrate the favorable resolution and reliability of the system for in vivo on
      line monitoring.

PMID- 11959482
TI  - A miniature fiber optic surface plasmon resonance sensor for fast detection of
      Staphylococcal enterotoxin B.
AB  - A fiber optic surface plasmon resonance (SPR) biosensor for detection of
      Staphylococcal enterotoxin B (SEB) is reported. The sensor is based on spectral
      interrogation of surface plasmons in a miniature sensing element based on a side
      polished single-mode optical fiber with a thin metal overlayer. For specific
      detection of SEB, the SPR sensor is functionalized with a covalently crosslinked
      double-layer of antibodies against SEB. The SPR biosensor is demonstrated to be
      able to detect ng/ml concentrations of SEB in less than 10 min.

PMID- 11959483
TI  - Micromolded PDMS planar electrode allows patch clamp electrical recordings from
      cells.
AB  - The patch clamp method measures membrane currents at very high resolution when a
      high-resistance 'gigaseal' is established between the glass microelectrode and
      the cell membrane (Pflugers Arch. 391 (1981) 85; Neuron 8 (1992) 605). Here we
      describe the first use of the silicone elastomer, poly(dimethylsiloxane) (PDMS),
      for patch clamp electrodes. PDMS is an attractive material for patch clamp
      recordings. It has low dielectric loss and can be micromolded (Annu. Rev. Mat.
      Sci. 28 (1998) 153) into a shape that mimics the tip of the glass micropipette.
      Also, the surface chemistry of PDMS may be altered to mimic the hydrophilic
      nature of glass (J. Appl. Polym. Sci. 14 (1970) 2499; Annu. Rev. Mat. Sci. 28
      (1998) 153), thereby allowing a high-resistance seal to a cell membrane. We
      present a planar electrode geometry consisting of a PDMS partition with a small
      aperture sealed between electrode and bath chambers. We demonstrate that a planar
      PDMS patch electrode, after oxidation of the elastomeric surface, permits patch
      clamp recording on Xenopus oocytes. Our results indicate the potential for high
      throughput patch clamp recording with a planar array of PDMS electrodes.

PMID- 11959484
TI  - An integrated, stacked microlaboratory for biological agent detection with DNA
      and immunoassays.
AB  - An integrated, stacked microlaboratory for performing automated electric-field
      driven immunoassays and DNA hybridization assays was developed. The stacked
      microlaboratory was fabricated by orderly laminating several different functional
      layers (all 76 x 76 mm(2)) including a patterned polyimide layer with a flip-chip
      bonded CMOS chip, a pressure sensitive acrylic adhesive (PSA) layer with a
      fluidic cutout, an optically transparent polymethyl methacrylate (PMMA) film, a
      PSA layer with a via, a patterned polyimide layer with a flip-chip bonded silicon
      chip, a PSA layer with a fluidic cutout, and a glass cover plate layer.
      Versatility of the stacked microlaboratory was demonstrated by various automated
      assays. Escherichia coli bacteria and Alexa-labeled protein toxin staphylococcal
      enterotoxin B (SEB) were detected by electric-field-driven immunoassays on a
      single chip with a specific-to-nonspecific signal ratios of 4.2:1 and 3.0:1,
      respectively. Furthermore, by integrating the microlaboratory with a module for
      strand displacement amplification (SDA), the identification of the Shiga-like
      toxin gene (SLT1) from E. coli was accomplished within 2.5 h starting from a
      dielectrophoretic concentration of intact E. coli bacteria and finishing with an
      electric-field-driven DNA hybridization assay, detected by fluorescently labeled
      DNA reporter probes. The integrated microlaboratory can be potentially used in a
      wide range of applications including detection of bacteria and biowarfare agents,
      and genetic identification.

PMID- 11959485
TI  - A signal process method for DNA segments separation in micro-channel
      electrophoresis.
AB  - This paper presents a signal process method for DNA segments separation in micro
      channel electrophoresis. It is developed and optimized by using a laser induced
      fluorescence (LIF) based detection system. In this detection system, signal is
      sampled and processed through a novel signal process module. The results show
      that this signal process method provides good signal-to-noise ratios and lower
      limit of detection (LOD).

PMID- 11959486
TI  - Sensing technologies for contaminated sites and groundwater.

PMID- 11959490
TI  - Theoretical and computational advances in biomolecular NMR spectroscopy.
AB  - Recent developments in experimental and computational aspects of NMR spectroscopy
      have had a significant impact on the accuracy and speed of macromolecular
      structure determination in solution, particularly with regard to systems of high
      complexity (such as protein complexes). These include experiments designed to
      provide long-range orientational and translational restraints, improvements in
      internal coordinate dynamics used for simulated annealing, and the development of
      database potentials of mean force to improve the description of the non-bonded
      contacts.

PMID- 11959491
TI  - Modeling supramolecular assemblages.
AB  - There has been some progress (but not much) in simulating supramolecular
      assemblages in the past year. The two main technical advances have been, firstly,
      the establishment of a protocol for extracting equilibrium thermodynamic data
      from forced (i.e. nonequilibrium) simulations and experiments, and, secondly, the
      development of a method for accurately calculating the electrostatics of enormous
      systems. Some recent applications have demonstrated the increasing feasibility of
      performing meaningful simulations of very large systems.

PMID- 11959492
TI  - Protein folding: the free energy surface.
AB  - Quantitative models and experiments are revealing how the folding free energy
      surface of a protein is sculpted by sequence and environment. The sometimes
      conflicting demands of folding, structure and function determine which folding
      pathways, if any, dominate. Recent advances include experimental estimates of
      diffusive barrier-crossing times, the observation of ultrafast folders amenable
      to full-atom simulation, the use of thermodynamic tuning and nonconservative
      mutations to probe 'hidden' parts of the free energy surface, and a complete
      microscopic theory of folding.

PMID- 11959493
TI  - Electronic excitations of biomolecules studied by quantum chemistry.
AB  - Significant methodological advances have been made over the past ten years in
      developing reliable quantum chemical methods for the treatment of electronically
      excited states. These methods can nowadays be used routinely by the experienced
      researcher to accurately compute excitation spectra of medium-sized organic
      molecules; results have been reported for several popular photobiological
      systems, including green fluorescent protein. First steps are currently being
      taken to account for the solvochromic shifts of chromophore excitations caused by
      particular protein environments and to dynamically simulate photochemical
      reactions in the excited states.

PMID- 11959494
TI  - Ab initio protein structure prediction.
AB  - Steady progress has been made in the field of ab initio protein folding. A
      variety of methods now allow the prediction of low-resolution structures of small
      proteins or protein fragments up to approximately 100 amino acid residues in
      length. Such low-resolution structures may be sufficient for the functional
      annotation of protein sequences on a genome-wide scale. Although no consistently
      reliable algorithm is currently available, the essential challenges to developing
      a general theory or approach to protein structure prediction are better
      understood. The energy landscapes resulting from the structure prediction
      algorithms are only partially funneled to the native state of the protein. This
      review focuses on two areas of recent advances in ab initio structure prediction
      improvements in the energy functions and strategies to search the caldera region
      of the energy landscapes.

PMID- 11959495
TI  - Theoretical and computational models of ion channels.
AB  - Computational studies can make meaningful contributions to our understanding of
      biological ion channels. A wide variety of methods, at different levels of
      approximation, can be used. Over the past few years, progress in the experimental
      determination of three-dimensional structures has given a fresh impetus to the
      theorists. Noteworthy progress has been made in carefully constructing realistic
      models of a number of complex biological channels to address important questions
      about their function.

PMID- 11959496
TI  - Molecular dynamics simulations.
AB  - Molecular dynamics simulations have become a standard tool for the investigation
      of biomolecules. Simulations are performed of ever bigger systems using more
      realistic boundary conditions and better sampling due to longer sampling times.
      Recently, realistic simulations of systems as complex as transmembrane channels
      have become feasible. Simulations aid our understanding of biochemical processes
      and give a dynamic dimension to structural data; for example, the transformation
      of harmless prion protein into the disease-causing agent has been modeled.

PMID- 11959497
TI  - Complexity and simplicity of ligand-macromolecule interactions: the energy
      landscape perspective.
AB  - The energy landscape approach has contributed to recent progress in understanding
      the complexity and simplicity of ligand-macromolecule interactions. Significant
      advances in computational structure prediction of ligand-protein complexes have
      been made using approaches that include the effects of protein flexibility and
      incorporate a hierarchy of energy functions. The results suggest that the
      complexity of structure prediction in molecular recognition may be determined by
      low-resolution properties of the underlying binding energy landscapes and by the
      nature of the energy funnels near the native structures of the complexes.

PMID- 11959498
TI  - Biomolecular diffusional association.
AB  - The primary method for the computational study of biomolecular diffusional
      association is Brownian dynamics. Recent work has seen advances in the efficiency
      of computing association rates and in the accuracy of simulation models. New
      areas to which Brownian dynamics has been applied include protein polymerisation
      and protein adsorption to a surface. There has recently been particularly intense
      study of protein-protein association, and Brownian dynamics, together with other
      theoretical and experimental approaches, has led to new insights into the
      determinants of protein-protein binding kinetics.

PMID- 11959500
TI  - Clamp loaders and sliding clamps.
AB  - A coherent view of the structure and function of DNA polymerase processivity
      factors (sliding clamps and clamp loaders) is emerging from recent structural
      studies. Crystal structures of sliding clamps from the T4 and RB69
      bacteriophages, and from an archaebacterium expand the gallery of ring-shaped
      processivity factors and clarify how the clamp interacts with the DNA polymerase.
      Crystallographic and electron microscopic views of clamp loaders from bacteria,
      archaebacteria and eukaryotes emphasize their common architecture and have
      produced models of how ATPbinding might be coupled to clamp opening/loading.

PMID- 11959501
TI  - Transcription factor complexes.
AB  - Considerable progress has been made during the past year on structural studies of
      the eukaryotic and bacterial transcription factors that control RNA polymerase
      function via the formation of multiprotein complexes on promoter DNA. Recently
      determined structures include negative cofactor 2 recognizing a preformed TATA
      box-binding protein-DNA binary complex, a dimer of BmrR bound to both DNA and
      tetra-phenylphosphonium, DNA-bound complexes of SarA and FadR, leukemia
      associated AML1-CBFbeta-DNA ternary complexes and a SAP1-SRF-DNA ternary complex.

PMID- 11959502
TI  - Machinery of protein folding and unfolding.
AB  - During the past two years, a large amount of biochemical, biophysical and low- to
      high-resolution structural data have provided mechanistic insights into the
      machinery of protein folding and unfolding. It has emerged that dual
      functionality in terms of folding and unfolding might exist for some systems. The
      majority of folding/unfolding machines adopt oligomeric ring structures in a
      cooperative fashion and utilise the conformational changes induced by ATP
      binding/hydrolysis for their specific functions.

PMID- 11959503
TI  - Membrane protein complexes.
AB  - A wide range of membrane protein structures have been published during the past
      two years. These have included proteins from both eucaryotic and heterologously
      overexpressed sources. Whereas some of these proteins were crystallised using
      conventional techniques, others employed the new methods of lipidic cubic phase
      crystallisation and antibody fragment co-crystallisation. These and other new
      approaches to the expression and crystallisation of membrane proteins are
      accelerating structural studies of membrane protein complexes.

PMID- 11959504
TI  - The assembly of protein subunits and cofactors in photosystem I.
AB  - The recently determined crystal structures of photosystems I and II at 2.5 A and
      3.8 A resolution, respectively, have improved the structural basis for
      understanding the processes of light trapping, exciton transfer and electron
      transfer occurring in the primary steps of oxygenic photosynthesis. Understanding
      the assembly of the 12 protein subunits and 128 cofactors in photosystem I allows
      us to study the possible functions of the individual players in this protein
      cofactor complex.

PMID- 11959506
TI  - Deriving folds of macromolecular complexes through electron cryomicroscopy and
      bioinformatics approaches.
AB  - Intermediate-resolution (7-9A) structures of large macromolecular complexes can
      be obtained by electron cryomicroscopy. This structural information, combined
      with bioinformatics data for the individual protein components or domains, can
      lead to a fold model for the entire complex. Such approaches have been
      demonstrated with the 6.8 A structure of the rice dwarf virus to derive models
      for the major capsid shell proteins.

PMID- 11959505
TI  - The cytoplasmic face of cell contact sites.
AB  - The cytoplasmic face of cell contact sites comprises large macromolecular
      assemblies that link transmembrane cell adhesion molecules to the cytoskeleton.
      These assemblies are dynamic structures that are the targets of regulatory
      signals that control cell adhesiveness. Recent studies of the biochemistry and
      structure of the cadherin-catenin complex, vinculin and proteins of the
      ezrin/radixin/moesin family have begun to reveal the architecture of these
      assemblies and the mechanisms that are involved in their regulation.

PMID- 11959507
TI  - Introduction: regulation of lymphocyte homeostasis.

PMID- 11959508
TI  - Homeostatic expansion versus antigen-driven proliferation: common ends by
      different means?
AB  - The requirements for T-cell proliferation driven by "space-filling" (homeostatic
      expansion) differ significantly from those for antigen-driven responses. Here we
      review these differences and discuss their implications for regulation of T-cell
      responses and the size of the T-cell compartment.

PMID- 11959509
TI  - Maintaining the status quo: T-cell homeostasis.
AB  - Lymphocyte numbers and subset composition are maintained at relatively constant
      levels throughout adulthood. Fluctuations in cell numbers due to infection, loss
      of cells, or other influences are smoothed out by unknown mechanisms that return
      the system to homeostasis. Regulation of lymphocyte numbers could be controlled
      at several points: rate of production, alteration in life span by diminution or
      enhancement of survival, or by division of cells within the compartment. Cell
      numbers within the immune system appear to be controlled by homeostatic
      mechanisms that influence each of these points. This discussion will focus on the
      regulation of peripheral cell numbers by the antigen-independent proliferation of
      T cells, which has recently been demonstrated to contribute to the maintenance
      and recovery of lymphocyte homeostasis.

PMID- 11959510
TI  - MHC-dependent survival of naive T cells? A complicated answer to a simple
      question.
AB  - The differentiation and survival of developing alpha beta thymocytes depends on
      effective T-cell receptor (TCR) signaling upon recognition of self peptide/major
      histocompatibility complex (MHC) molecule ligands. Although this concept is
      uniformly accepted with regard to immature thymocytes, there are conflicting
      reports as to whether or not MHC recognition is required for survival of mature
      peripheral naive T cells. In this review, we assess these reports critically and
      conclude that in many cases, the differences observed in CD4(+) T-cell recovery
      between MHC-expressing and MHC-deficient animals can be attributed to
      proliferation occurring only in the MHC-expressing lymphopenic animals studied in
      these models systems, rather than to effects of MHC recognition on cell viability
      per se. Still other reports involve experimental manipulations that may have
      affected the intrathymic development of the T cells such that they receive a
      "poor" selecting signal, fail to fully mature, and thus behave more like
      thymocytes in their survival characteristics (i.e., show MHC dependence). With
      respect to CD8(+) T cells, we discuss data suggesting that some clones are more
      dependent upon the presence of MHC class I for survival than others. We propose
      that some CD8(+) T cells even in a wild-type host may behave like the manipulated
      CD4(+) T cells just described, and fail to mature completely with respect to
      their survival requirements. Although the proportion of CD8(+) cells in this MHC
      dependent state is not known, the corresponding fraction among CD4(+) T cells
      seems to be rather small. Overall, our analysis of the available data suggests
      that most or all mature CD4(+) (and perhaps also many CD8(+)) T lymphocytes do
      not depend on self-recognition for their viability in the periphery.

PMID- 11959511
TI  - Naive to memory T-cell differentiation during homeostasis-driven proliferation.
AB  - During homeostasis-driven T-cell proliferation, naive T cells stably acquire the
      cell surface markers and functional properties of antigen-induced memory T cells.
      Thus, in T-cell-deficient individuals, homeostasis-driven T-cell proliferation
      appears to restore only the memory T-cell compartment, whereas the reconstitution
      of the naive T-cell compartment depends on de novo T-cell development in the
      thymus.

PMID- 11959512
TI  - The puzzling world of murine T regulatory cells.
AB  - T regulatory cells are essential for downregulation of undesired immune responses
      and prevention of autoimmune diseases, organ rejection, and graft versus host
      disease. This review describes the considerable progress made in the recent years
      in the characterization of the many subsets that constitute the puzzled world of
      murine T regulatory cells.

PMID- 11959513
TI  - Homeostasis of intestinal immune regulation.
AB  - Regulatory CD4 T cells with the capacity to inhibit potentially harmful immune
      responses have been described in various experimental systems. Although the
      observations are converging towards the naturally activated CD25(+) CD4 T cells
      as a major population responsible for this protection, there is still
      considerable disagreement on the molecular and cellular requirements involved to
      achieve a stable immune homeostasis in vivo.

PMID- 11959515
TI  - Fighting restenosis from the inside out.

PMID- 11959514
TI  - Plasticity of lymphoid compartments during HIV infection and treatments: hopes
      and limits.
AB  - Immune reconstitution during antiretroviral therapy has recently been shown to
      depend upon multiple factors at work in T-cell homeostasis, amongst which the
      reduction of thymus dysfunction and of immune hyperactivation is instrumental.
      The restoration of host defenses against opportunistic pathogens is, however,
      balanced by the poor immunity restored against HIV thus giving a satisfying link
      between antigen stimulation and the reconstitution of immune responses to
      pathogens.

PMID- 11959516
TI  - Who should be taking aspirin?

PMID- 11959518
TI  - Heart lines. Angioplasty vs. bypass.

PMID- 11959517
TI  - Chelation therapy.

PMID- 11959519
TI  - Ask the doctor. I've been diagnosed with atrial fibrillation. My daughter gave me
      a clipping from a natural health magazine that says the most common reason for
      this heart rhythm problem is magnesium deficiency. Is there any truth to this?

PMID- 11959520
TI  - Cancer. Support groups: study casts some doubt.

PMID- 11959521
TI  - Alcohol. Lift a glass (but not too many) to health.

PMID- 11959522
TI  - Eye Surgery. LASIK: buyer beware.

PMID- 11959523
TI  - Brain health. TIAs: heed these warning signs of stroke.

PMID- 11959524
TI  - By the way doctor... The doctor I've had for over 40 years just retired. I've
      found another one--he's awfully young, but it seems like everyone is these days!
      With a new doctor, do you think I need to get a complete physical? I'm 83, take
      medication to keep my blood pressure under control and lower my cholesterol, but
      I'm basically health--knock wood.

PMID- 11959525
TI  - By the way doctor... I have two perfectly good hearing aids, so my hearing
      wouldn't be so bad if it weren't for the huge buildup of earwax that makes them
      useless. It happens as quickly as two or three days after the doctor has cleaned
      out my ears. Is there anything I can do?

PMID- 11959526
TI  - The mind and the immune system--Part I.

PMID- 11959527
TI  - Drug treatments for alcoholism.

PMID- 11959528
TI  - Brain tissue loss in schizophrenia.

PMID- 11959530
TI  - Personality and cancer.

PMID- 11959531
TI  - Should you have a stress test before you exercise?

PMID- 11959529
TI  - Trends in smoking and their meaning.

PMID- 11959532
TI  - Bladder cancer.

PMID- 11959533
TI  - Knocked cold: a concussion discussion.

PMID- 11959534
TI  - On call. I'm a 62-year-old man in good health. I take Zocor for my cholesterol as
      well as a baby aspirin and several vitamins every day. My problem may seem silly,
      but it's really a nuisance: uncontrollable yawning. Do you have any idea why I
      yawn so much or what I can do about it?

PMID- 11959536
TI  - Chronic conditions. How to cope with COPD.

PMID- 11959535
TI  - Guidelines target many women for statins.

PMID- 11959537
TI  - Dermatology. What skin creams can and can't do.

PMID- 11959538
TI  - New breast cancer drugs expand treatment options.

PMID- 11959539
TI  - Vive la difference: women's sense of smell.

PMID- 11959540
TI  - By the way, doctor. Your article about anxiety in the March 2002 issue neglected
      to mention the herb kava as a treatment for anxiety. I've been using it, and I
      thought its effectiveness for anxiety was widely accepted. Why did you omit it?

PMID- 11959543
TI  - TEM-80, a novel inhibitor-resistant beta-lactamase in a clinical isolate of
      Enterobacter cloacae.
AB  - Enterobacter cloacae Ecl261 was isolated with Escherichia coli Ec257 from the
      urine of a patient living in a nursing home. Both isolates were resistant to
      ticarcillin (MICs, 1,024 microg/ml), without significant potentiation of its
      activity by 2 microg of clavulanate per ml (MICs, 512 microg/ml), and susceptible
      to naturally active cephalosporins. This inhibitor-resistant phenotype was
      conferred in both strains by similar conjugative plasmids of 40 kb (Ecl261) and
      30 kb (Ec257), which also conveyed resistance to sulfonamides and trimethoprim.
      Clinical and transconjugant strains produced a beta-lactamase with a pI of 5.2
      which belonged to the TEM family, as indicated by specific PCR amplification.
      Compared with TEM-1, this enzyme exhibited lower catalytic efficiencies (14- and
      120-fold less for amoxicillin and ticarcillin, respectively), and higher
      concentrations of beta-lactamase inhibitors were required to yield a 50%
      reduction in benzylpenicillin hydrolysis (750-, 82-, and 50-fold higher
      concentrations for clavulanate, sulbactam, and tazobactam, respectively). Gene
      sequencing revealed four nucleotide differences with the nucleotide sequence of
      bla(TEM-1A). The first replacement (T32C), located in the promoter region, was
      described as being responsible for the increase in the level of beta-lactamase
      production. The three other changes led to amino acid substitutions that define a
      new inhibitor-resistant TEM (IRT) beta-lactamase, TEM-80 (alternate name, IRT
      24). Two of them, Met69Leu and Asn276Asp, have previously been related to
      inhibitor resistance. The additional mutation, Ile127Val, was demonstrated by
      site-directed mutagenesis to have a very weak effect, at least alone, on the IRT
      phenotype. This is the first description of an IRT beta-lactamase in E. cloacae.
      The horizontal transfer of bla(TEM-80) may have occurred either from Ec257 to
      Ecl261 or in the reverse order.

PMID- 11959542
TI  - Biosynthetic gene cluster of simocyclinone, a natural multihybrid antibiotic.
AB  - The entire simocyclinone biosynthetic cluster (sim gene cluster) from the
      producer Streptomyces antibioticus Tu6040 was identified on six overlapping
      cosmids (1N1, 5J10, 2L16, 2P6, 4G22, and 1K3). In total, 80.7 kb of DNA from
      these cosmids was sequenced, and the analysis revealed 49 complete open reading
      frames (ORFs). These ORFs include genes responsible for the formation and
      attachment of four different moieties originating from at least three different
      pools of primary metabolites. Also in the sim gene cluster, four ORFs were
      detected that resemble putative regulatory and export functions. Based on the
      putative function of the gene products, a model for simocyclinone D8 biosynthesis
      was proposed. Biosynthetic mutants were generated by insertional gene
      inactivation experiments, and culture extracts of these mutants were analyzed by
      high-performance liquid chromatography. Production of simocyclinone D8 was
      clearly detectable in the wild-type strain but was not detectable in the mutant
      strains. This indicated that indeed the sim gene cluster had been cloned.

PMID- 11959541
TI  - Antiparasitic agent atovaquone.

PMID- 11959544
TI  - Origin and evolution of the AmpC beta-lactamases of Citrobacter freundii.
AB  - To determine whether the widespread clinical use of beta-lactams has been
      selective for Citrobacter freundii-derived alleles of plasmid ampC genes, we
      generated a Bayesian consensus phylogeny of the published ampC sequences and
      compared the MICs of 16 beta-lactam antibiotics for Escherichia coli strains
      containing cloned copies of the C. freundii ampC alleles. We found that for the
      majority of compounds investigated, there has been essentially no increase in
      beta-lactam resistance conferred by those alleles. We also found that ampC
      alleles from the chromosomes of two beta-lactam-sensitive C. freundii strains
      isolated in the 1920s, before the clinical use of antibiotics, were as effective
      at providing beta-lactam resistance in E. coli as were the plasmid-borne alleles
      from beta-lactam-resistant clinical isolates. These results suggest that
      selection for increased resistance to beta-lactam antibiotics has not been a
      significant force directing the evolution of the C. freundii ampC alleles found
      in beta-lactam-resistant clinical isolates.

PMID- 11959545
TI  - Emergence of group A streptococcus strains with different mechanisms of macrolide
      resistance.
AB  - The mechanisms of resistance to macrolides in seven group A streptococcal
      (Streptococcus pyogenes) isolates that were the cause of pharyngitis in children
      who were unsuccessfully treated with azithromycin (10 mg/kg of body weight/day
      for 3 days) were evaluated. All posttreatment strains were found to be
      genetically related to the pretreatment isolates by random amplified polymorphism
      DNA analysis and pulsed-field gel electrophoresis. Two isolates had acquired
      either a mef(A) or an erm(B) gene, responsible for macrolide efflux and ribosomal
      modification, respectively. Three isolates displayed mutations in the gene
      encoding the L4 ribosomal protein that is part of the exit tunnel within the 50S
      subunit of the bacterial ribosome. In the two remaining posttreatment strains,
      the mechanisms of macrolide resistance could not be elucidated.

PMID- 11959546
TI  - Fitness cost of chromosomal drug resistance-conferring mutations.
AB  - To study the cost of chromosomal drug resistance mutations to bacteria, we
      investigated the fitness cost of mutations that confer resistance to different
      classes of antibiotics affecting bacterial protein synthesis (aminocyclitols, 2
      deoxystreptamines, macrolides). We used a model system based on an in vitro
      competition assay with defined Mycobacterium smegmatis laboratory mutants;
      selected mutations were introduced by genetic techniques to address the
      possibility that compensatory mutations ameliorate the resistance cost. We found
      that the chromosomal drug resistance mutations studied often had only a small
      fitness cost; compensatory mutations were not involved in low-cost or no-cost
      resistance mutations. When drug resistance mutations found in clinical isolates
      were considered, selection of those mutations that have little or no fitness cost
      in the in vitro competition assay seems to occur. These results argue against
      expectations that link decreased levels of antibiotic consumption with the
      decline in the level of resistance.

PMID- 11959547
TI  - ColE1-like plasmid pIP843 of Klebsiella pneumoniae encoding extended-spectrum
      beta-lactamase CTX-M-17.
AB  - The resistance of Klebsiella pneumoniae BM4493, isolated in Ho Chi Minh City,
      Vietnam, to cefotaxime and aztreonam was due to production of a novel beta
      lactamase, CTX-M-17. The bla(CTX-M-17) gene was borne by 7,086-bp plasmid pIP843,
      which was entirely sequenced and which was found to belong to the ColE1 family.
      The 876-bp bla(CTX-M-17) gene differed from bla(CTX-M-14) by 2 nucleotides, which
      led to the single amino acid substitution Glu289-->Lys. bla(CTX-M-17) was flanked
      upstream by an ISEcp1-like element and downstream by an insertion sequence (IS)
      IS903 variant designated IS903-C. The transcriptional start site of bla(CTX-M-17)
      was located 109 nucleotides upstream from the initiation codon in the ISEcp1-like
      element, which also provided the promoter sequences. Plasmid pIP843, which was
      non-self-transferable and nonmobilizable, contained five open reading frames
      transcribed in the same orientation. Regions homologous to sequences coding for
      putative RNA II and RNA I transcripts, a rom gene, which is involved in
      initiation of replication, and a cer-like gene, which is responsible for the
      stability of ColE1-like plasmids, were identified. Consensus sequences for
      putative replication (oriV) and transfer (oriT) origins were present. Results of
      primer extension experiments indicated that ISEcp1 provides the promoter for
      expression of bla(CTX-M-17) and may contribute to dissemination of this gene.

PMID- 11959548
TI  - Susceptibilities of Mycoplasma fermentans and Mycoplasma hyorhinis to membrane
      active peptides and enrofloxacin in human tissue cell cultures.
AB  - Mycoplasmas, which are bacteria that are devoid of a cell wall and which belong
      to the class Mollicutes, are pathogenic for humans and animals and are frequent
      contaminants of tissue cell cultures. Although contamination of cultures with
      mycoplasma can easily be monitored with fluorescent dyes that stain DNA and/or
      with molecular probes, protection and decontamination of cultures remain serious
      challenges. In the present work, we investigated the susceptibilities of
      Mycoplasma fermentans and Mycoplasma hyorhinis to the membrane-active peptides
      alamethicin, dermaseptin B2, gramicidin S, and surfactin by growth inhibition and
      lethality assays. In the absence of serum, the four peptides killed mycoplasmas
      at minimal bactericidal concentrations that ranged from 12.5 to 100 microM, but
      in all cases the activities were decreased by the presence of serum. As a result,
      under standard culture conditions (10% serum) only alamethicin and gramicidin S
      were able to inhibit mycoplasma growth (MICs, 50 microM), while dermaseptin B2
      and surfactin were ineffective. Furthermore, 8 days of treatment of HeLa cell
      cultures experimentally contaminated with either mycoplasma species with 70
      microM enrofloxacin cured the cultures of infection, whereas treatment with
      alamethicin and gramicidin S alone was not reliable because the concentrations
      and treatment times required were toxic to the cells. However, combination of
      alamethicin or gramicidin S with 70 microM enrofloxacin allowed mycoplasma
      eradication after 30 min or 24 h of treatment, depending on the mycoplasma and
      peptide considered. HeLa cell cultures experimentally infected with mycoplasmas
      should prove to be a useful model for study of the antimycoplasma activities of
      antibiotics and membrane-active peptides under conditions close to those found in
      vivo.

PMID- 11959549
TI  - Antibacterial activity of licochalcone A against spore-forming bacteria.
AB  - Licochalcone A was isolated from the roots of licorice, Glycyrrhiza inflata,
      which has various uses in the food and pharmaceutical industries; isolation was
      followed by extraction with ethanol and column chromatography with silica gel. In
      this study, the activities of licochalcone A against some food contaminant
      microorganisms were evaluated in vitro. The vegetative cell growth of Bacillus
      subtilis was inhibited in a licochalcone A concentration-dependent manner and was
      completely prevented by 3 micrograms of licochalcone A/ml. Licochalcone A showed
      a high level of resistance to heating at 80 to 121 degrees C for 15 min.
      Licochalcone A did not inhibit the germination of heat-treated spores of B.
      subtilis induced by L-alanine. Licochalcone A showed effects against all gram
      positive bacteria tested and especially was effective against all Bacillus spp.
      tested, with MICs of 2 to 3 micrograms/ml, but was not effective against gram
      negative bacteria or eukaryotes at 50 micrograms/ml. Although the cationic
      antimicrobial peptides protamine and epsilon-poly-L-lysine resulted in the loss
      of antimicrobial activity in the presence of either 3% (wt/vol) NaCl or protease
      at 20 micrograms/ml, the antibacterial activity of licochalcone A was resistant
      to these conditions. Thus, licochalcone A could be a useful compound for the
      development of antibacterial agents for the preservation of foods containing high
      concentrations of salts and proteases, in which cationic peptides might be less
      effective.

PMID- 11959550
TI  - Characterization of imidazo[4,5-d]pyridazine nucleosides as modulators of
      unwinding reaction mediated by West Nile virus nucleoside
      triphosphatase/helicase: evidence for activity on the level of substrate and/or
      enzyme.
AB  - Compounds that interact with DNA or RNA generally act as inhibitors of enzymes
      that unwind DNA or RNA. In the present study we describe the synthesis and
      properties of some nucleoside analogues that interact with double-stranded DNA
      but that, in contrast, facilitate the unwinding reaction mediated by West Nile
      (WN) virus nucleoside triphosphatase (NTPase)/helicase. The nucleoside analogues
      described, 1-(2'-O-methyl-beta-D-ribofuranosyl)imidazo[4,5-d]pyridazine
      4,7(5H,6H)-dione (HMC-HO4), 1-(beta-D-ribofuranosyl)imidazo[4,5-d]pyridazine
      4,7(5H,6H)-dione, and 1-(2'-deoxy-alpha-D-ribofuranosyl)imidazo[4,5-d]pyridazine
      4,7(5H,6H)dione, all contain the imidazo[4,5-d]pyridazine ring system. The extent
      of the enhancing effect on helicase activity was found to be dependent on the
      time of exposure of the DNA substrate to the compounds and their concentrations.
      The nucleoside analogues were nevertheless found to be capable of uncoupling the
      ATPase and helicase activities of the enzyme by a mechanism operating on the
      level of the enzyme. Thus, in the case of HMC-HO4, the direct interaction with
      the enzyme caused inhibition of its helicase activity, with a half-maximal
      inhibitory concentration of 30 microM. The similar potency of the compound
      against replication of WN virus in cell culture suggests that inhibition of the
      helicase activity of the viral enzyme is responsible for the observed antiviral
      activity of HMC-HO4 and may indeed represent an important mode of action of
      antiviral drugs in general. Comparative studies performed with the related
      NTPase/helicase from hepatitis C virus revealed that the extent of the effects
      mediated by imidazo[4,5-d]pyridazine nucleosides is enzyme specific. The
      substances described may represent a starting point for the development of a new
      class of helicase-specific antivirals.

PMID- 11959551
TI  - Efficacies of fluconazole, caspofungin, and amphotericin B in Candida glabrata
      infected p47phox-/- knockout mice.
AB  - Candida glabrata is the second leading cause of adult candidemia, resulting in
      high mortality. Amphotericin B is considered the treatment of choice, while the
      efficacy of fluconazole is controversial and caspofungin efficacy is unknown. To
      ascertain drug efficacy in vivo, the utility of a murine model of C. glabrata
      infection was investigated. C. glabrata was found to cause progressive, lethal
      infection when injected intravenously into C57BL/6 mice with reduced oxidative
      microbicidal capacity due to knockout of the p47(phox) gene. Spleen and kidney
      organ CFU counts were determined in groups of mice 2 days after the mice
      completed 6 days of daily intraperitoneal drug treatment, which began on the day
      of infection. Daily injections of fluconazole at 80 mg/kg did not reduce spleen
      or kidney CFU counts after infection with C. glabrata strains having in vitro
      fluconazole MICs of 2, 32, or 256 microg/ml compared to saline-treated controls.
      However, this fluconazole regimen reduced spleen CFU counts in mice infected with
      Candida albicans, an infection that is known to be responsive to fluconazole.
      Caspofungin at 5 mg/kg and amphotericin B at 5 mg/kg were both effective in
      reducing fungal burden in spleens and kidneys of C. glabrata-infected mice. Ten
      mice treated for 6 days with caspofungin at 1 mg/kg survived for 15 days, though
      all 10 saline-injected mice died or were so ill that they had to be sacrificed by
      96 h postinfection. This murine model provided evidence of the efficacy of
      amphotericin B and caspofungin but not of fluconazole against C. glabrata
      infection.

PMID- 11959552
TI  - A missense mutation in the fabB (beta-ketoacyl-acyl carrier protein synthase I)
      gene confers tiolactomycin resistance to Escherichia coli.
AB  - Thiolactomycin (TLM) is an antibiotic that inhibits bacterial type II fatty acid
      synthesis at the condensing enzyme step, and beta-ketoacyl-acyl carrier protein
      synthase I (FabB) is the relevant target in Escherichia coli. TLM resistance is
      associated with the upregulation of efflux pumps. Therefore, a tolC knockout
      mutant (strain ANS1) was constructed to eliminate the contribution of type I
      secretion systems to TLM resistance. Six independent TLM-resistant clones of
      strain ANS1 were isolated, and all possessed the same missense mutation in the
      fabB gene (T1168G) that directed the expression of a mutant protein, FabB(F390V).
      FabB(F390V) was resistant to TLM in vitro. Leucine is the only other amino acid
      found at position 390 in nature, and the Staphylococcus aureus FabF protein,
      which contains this substitution, was sensitive to TLM. Structural modeling
      predicted that the CG2 methyl group of the valine side chain interfered with the
      positioning of the C11 methyl on the isoprenoid side chain of TLM in the binary
      complex, whereas the absence of a bulky methyl group on the leucine side chain
      permitted TLM binding. These data illustrate that missense mutations that
      introduce valine at position 390 confer TLM resistance while maintaining the
      vital catalytic properties of FabB.

PMID- 11959553
TI  - Identification of essential residues in the Erm(B) rRNA methyltransferase of
      Clostridium perfringens.
AB  - Macrolide-lincosamide-streptogramin B resistance is widespread, with the
      determinants encoding resistance to antibiotics such as erythromycin being
      detected in many bacterial pathogens. Resistance is most commonly mediated by the
      production of an Erm protein, a 23S rRNA methyltransferase. We have undertaken a
      mutational analysis of the Erm(B) protein from Clostridium perfringens with the
      objective of developing a greater understanding of the mechanism of action of
      this protein. A recombinant plasmid that carried the erm(B) gene was mutated by
      either in vitro hydroxylamine mutagenesis or passage through the mutator strain
      XL1-Red. Twenty-eight independently derived mutants were identified, nine of
      which had single point mutations in the erm(B) gene. These mutants produced
      stable but nonfunctional Erm(B) proteins, and all had amino acid changes within
      conserved methyltransferase motifs that were important for either substrate
      binding or catalysis. Modeling of the C. perfringens Erm(B) protein confirmed
      that the point mutations all involved residues important for the structure and/or
      function of this rRNA methyltransferase. These regions of the protein therefore
      represent potential targets for the rational development of methyltransferase
      inhibitors.

PMID- 11959554
TI  - NB2001, a novel antibacterial agent with broad-spectrum activity and enhanced
      potency against beta-lactamase-producing strains.
AB  - Enzyme-catalyzed therapeutic activation (ECTA) is a novel prodrug strategy to
      overcome drug resistance resulting from enzyme overexpression. beta-Lactamase
      overexpression is a common mechanism of bacterial resistance to beta-lactam
      antibiotics. We present here the results for one of the beta-lactamase ECTA
      compounds, NB2001, which consists of the antibacterial agent triclosan in a
      prodrug form with a cephalosporin scaffold. Unlike conventional beta-lactam
      antibiotics, where hydrolysis of the beta-lactam ring inactivates the antibiotic,
      hydrolysis of NB2001 by beta-lactamase releases triclosan. Evidence supporting
      the proposed mechanism is as follows. (i) NB2001 is a substrate for TEM-1 beta
      lactamase, forming triclosan with a second-order rate constant (k(cat)/K(m)) of
      greater than 77,000 M-1 s-1. (ii) Triclosan is detected in NB2001-treated, beta
      lactamase-producing Escherichia coli but not in E. coli that does not express
      beta-lactamase. (iii) NB2001 activity against beta-lactamase-producing E. coli is
      decreased in the presence of the beta-lactamase inhibitor clavulanic acid. NB2001
      was similar to or more potent than reference antibiotics against clinical
      isolates of Staphylococcus aureus (including MRSA), Staphylococcus epidermidis,
      Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis, Moraxella
      catarrhalis and Haemophilus influenzae. NB2001 is also active against Klebsiella
      pneumoniae, Enterobacter aerogenes, and Enterobacter cloacae. The results
      indicate that NB2001 is a potent, broad-spectrum antibacterial agent and
      demonstrate the potential of ECTA in overcoming beta-lactamase-mediated
      resistance.

PMID- 11959555
TI  - Characterization of plasmids carrying CMY-2 from expanded-spectrum cephalosporin
      resistant Salmonella strains isolated in the United States between 1996 and 1998.
AB  - Sequencing of DNA from 15 expanded-spectrum cephalosporin (e.g., ceftriaxone)
      resistant Salmonella isolates obtained in the United States revealed that
      resistance to ceftriaxone in all isolates was mediated by cmy-2. Hybridization
      patterns revealed three plasmid structures containing cmy-2 in these 15 isolates.
      These data suggest that the spread of cmy-2 among Salmonella strains is occurring
      through mobilization of the cmy-2 gene into different plasmid backbones and
      consequent horizontal transfer by conjugation.

PMID- 11959556
TI  - Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b,
      and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren,
      cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin
      susceptible, -intermediate, and -resistant pneumococci.
AB  - Amino acid alterations in or flanking conserved motifs making up the active
      binding sites of penicillin-binding proteins (PBPs) 1a, 2b, and 2x of pneumococci
      were correlated with changes in affinities of penicillin, ampicillin,
      amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor for these PBPs. Four
      penicillin-susceptible (PSSP), eight penicillin-intermediate (PISP), and six
      penicillin-resistant (PRSP) pneumococci were studied by DNA sequencing of the
      penicillin-binding sites of the pbp1a, -2x, and -2b genes of strains and by
      determining 50% inhibitory concentrations of the seven agents for PBP1a, -2x, and
      -2b. Two PSSP strains had alterations in PBP2x (L(546)-->V) (one strain) or PBP2b
      (T(445)-->A) (one strain). All eight PISP strains had at least two alterations-
      T(338)-->P or A or H(394)-->Y in PBP2X and T(445)-->A in BPB2b. All PRSP strains
      had the same changes seen in PISP strains, as well as T(371)-->A or S
      substitutions in PBP1a. The two most resistant PRSP strains had a second change
      in PBP2x (M(339)-->F) in a conserved motif. The affinities of penicillin and
      ampicillin for all three PBPs were decreased for PRSP and most PISP strains. The
      affinity of amoxicillin for PBP1a and -2x was decreased only for PRSP. Cefaclor
      and cefprozil showed decreased affinity of PRSP but not PISP for all three PBPs.
      Cefuroxime showed decreased affinity of PISP and PRSP for PBP1a and -2x but no
      change for PBP2b. Cefditoren showed no difference in PBP affinity based on
      penicillin or cefditoren MICs, indicating a different PBP target for this agent.
      Overall, the MICs for and PBP affinities of the strains correlated with the
      changes found in the PBP active binding sites.

PMID- 11959557
TI  - Widespread distribution of a tet W determinant among tetracycline-resistant
      isolates of the animal pathogen Arcanobacterium pyogenes.
AB  - Tetracycline resistance is common among isolates of the animal commensal and
      opportunistic pathogen Arcanobacterium pyogenes. The tetracycline resistance
      determinant cloned from two bovine isolates of A. pyogenes was highly similar at
      the DNA level (92% identity) to the tet(W) gene, encoding a ribosomal protection
      tetracycline resistance protein, from the rumen bacterium Butyrivibrio
      fibrisolvens. The tet(W) gene was found in all 20 tetracycline-resistant isolates
      tested, indicating that it is a widely distributed determinant of tetracycline
      resistance in this organism. In 25% of tetracycline-resistant isolates, the
      tet(W) gene was associated with a mob gene, encoding a functional mobilization
      protein, and an origin of transfer, suggesting that the determinant may be
      transferable to other bacteria. In fact, low-frequency transfer of tet(W) was
      detected from mob+ A. pyogenes isolates to a tetracycline-sensitive A. pyogenes
      recipient. The mobile nature of this determinant and the presence of A. pyogenes
      in the gastrointestinal tract of cattle and pigs suggest that A. pyogenes may
      have inherited this determinant within the gastrointestinal tracts of these
      animals.

PMID- 11959558
TI  - Characterization and movement of the class 1 integron known as Tn2521 and Tn1405.
AB  - Two putative transposons, Tn2521 and Tn1405, carrying determinants for the PSE-4
      beta-lactamase and for resistance to streptomycin, spectinomycin, and
      sulfonamides were previously isolated from the chromosome of Pseudomonas
      aeruginosa Dalgleish. Detailed mapping and determination of the complete sequence
      of Tn2521 revealed that it is a class 1 integron, here renamed In33, with a
      backbone structure identical to that of In4 from Tn1696. In33 contains two gene
      cassettes, blaP1 and aadA1, replacing the aacC1-orfE-aadA2-cmlA1 cassette array
      in In4. Although In33 does not include any transposition genes, movement of In33
      (Tn2521) targeted to a single location in the IncP-1 plasmid R18-18 has been
      reported previously (M. I. Sinclair and B. W. Holloway, J. Bacteriol. 151:569
      579, 1982). A 5-bp duplication of the target, which lies within the res site
      recognized by the ParA resolvase of R18-18, was present, indicating that the
      mechanism of movement was transposition. Together, these data indicate that class
      1 integrons that are defective in self-transposition can move under appropriate
      circumstances. The Tn1405 isolate studied was found to represent only the
      cassette array of In33, which had replaced the cassette array in the recipient
      plasmid R388, probably by homologous recombination.

PMID- 11959559
TI  - Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in
      Canada during 2000.
AB  - A total of 2,245 clinical isolates of Streptococcus pneumoniae were collected
      from 63 microbiology laboratories from across Canada during 2000 and
      characterized at a central laboratory. Of these isolates, 12.4% were not
      susceptible to penicillin (penicillin MIC, >or=0.12 microg/ml) and 5.8% were
      resistant (MIC, >or=2 microg/ml). Resistance rates among non-beta-lactam agents
      were the following: macrolides, 11.1%; clindamycin, 5.7%; chloramphenicol, 2.2%;
      levofloxacin, 0.9%; gatifloxacin, 0.8%; moxifloxacin, 0.4%; and trimethoprim
      sulfamethoxazole, 11.3%. The MICs at which 90% of the isolates were inhibited
      (MIC90s) of the fluoroquinolones were the following: gemifloxacin, 0.03
      microg/ml; BMS-284756, 0.06 microg/ml; moxifloxacin, 0.12 microg/ml;
      gatifloxacin, 0.25 microg/ml; levofloxacin, 1 microg/ml; and ciprofloxacin, 1
      microg/ml. Of 578 isolates from the lower respiratory tract, 21 (3.6%) were
      inhibited at ciprofloxacin MICs of >or=4 microg/ml. None of the 768 isolates from
      children were inhibited at ciprofloxacin MICs of >or=4 microg/ml, compared to 3
      of 731 (0.6%) from those ages 15 to 64 (all of these >60 years old), and 27 of
      707 (3.8%) from those over 65. The MIC90s for ABT-773 and telithromycin were
      0.015 microg/ml for macrolide-susceptible isolates and 0.12 and 0.5 microg/ml,
      respectively, for macrolide-resistant isolates. The MIC of linezolid was <or=2
      microg/ml for all isolates. Many of the new antimicrobial agents tested in this
      study appear to have potential for the treatment of multidrug-resistant strains
      of pneumococci.

PMID- 11959560
TI  - Effects of compounds found in propolis on Streptococcus mutans growth and on
      glucosyltransferase activity.
AB  - Propolis, a resinous bee product, has been shown to inhibit the growth of oral
      microorganisms and the activity of bacterium-derived glucosyltransferases (GTFs).
      Several compounds, mainly polyphenolics, have been identified in this natural
      product. The present study evaluated the effects of distinct chemical groups
      found in propolis on the activity of GTF enzymes in solution and on the surface
      of saliva-coated hydroxyapatite (sHA) beads. Thirty compounds, including
      flavonoids, cinnamic acid derivatives, and terpenoids, were tested for the
      ability to inhibit GTFs B, C, and D from Streptococcus mutans and GTF from S.
      sanguinis (GTF Ss). Flavones and flavonols were potent inhibitors of GTF activity
      in solution; lesser effects were noted on insolubilized enzymes. Apigenin, a
      4',5,7-trihydroxyflavone, was the most effective inhibitor of GTFs, both in
      solution (90.5 to 95% inhibition at a concentration of 135 microg/ml) and on the
      surface of sHA beads (30 to 60% at 135 microg/ml). Antibacterial activity was
      determined by using MICs, minimum bactericidal concentrations (MBCs), and time
      kill studies. Flavanones and some dihydroflavonols, as well as the sesquiterpene
      tt-farnesol, inhibited the growth of S. mutans and S. sobrinus; tt-farnesol was
      the most effective antibacterial compound (MICs of 14 to 28 microg/ml and MBCs of
      56 to 112 microg/ml). tt-Farnesol (56 to 112 microg/ml) produced a 3-log-fold
      reduction in the bacterial population after 4 h of incubation. Cinnamic acid
      derivatives had negligible biological activities. Several of the compounds
      identified in propolis inhibit GTF activities and bacterial growth. Apigenin is a
      novel and potent inhibitor of GTF activity, and tt-farnesol was found to be an
      effective antibacterial agent.

PMID- 11959561
TI  - Purification, characterization, and identification of novel inhibitors of the
      beta-ketoacyl-acyl carrier protein synthase III (FabH) from Staphylococcus
      aureus.
AB  - Staphylococcus aureus is a versatile and dangerous pathogen and one of the major
      causes of community-acquired and hospital-acquired infections. The rise of
      multidrug-resistant strains of S. aureus requires the development of new
      antibiotics with previously unexploited mechanisms of action, such as inhibition
      of the beta-ketoacyl-acyl carrier protein (ACP) synthase III (FabH). This enzyme
      initiates fatty acid biosynthesis in a bacterial type II fatty acid synthase,
      catalyzing a decarboxylative condensation between malonyl-ACP and an acyl
      coenzyme A (CoA) substrate and is essential for viability. We have identified
      only one fabH in the genome of S. aureus and have shown that it encodes a protein
      with 57, 40, and 34% amino acid sequence identity with the FabH proteins of
      Bacillus subtilis (bFabH1), Escherichia coli (ecFabH), and Mycobacterium
      tuberculosis (mtFabH). Additional genomic sequence analysis revealed that this S.
      aureus FabH (saFabH) is not mutated in certain methicillin-resistant S. aureus
      (MRSA) and vancomycin-resistant S. aureus (VRSA) strains. saFabH was expressed in
      E. coli with an N-terminal polyhistidine tag and subsequently purified by metal
      chelate and size exclusion chromatography. Analysis by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis revealed a molecular mass of 37 kDa, while gel
      filtration demonstrated a mass of 66.7 kDa, suggesting a noncovalent homodimeric
      structure for saFabH. The apparent K(m) for malonyl-ACP was 1.76 +/- 0.40 microM,
      and the enzyme was active with acetyl-CoA (k(cat), 16.18 min(-1); K(m), 6.18 +/-
      0.9 microM), butyryl-CoA (k(cat), 42.90 min(-1); K(m), 2.32 +/- 0.12 microM), and
      isobutyryl-CoA (k(cat), 98.0 min(-1); K(m), 0.32 +/- 0.04 microM). saFabH was
      weakly inhibited by thiolactomycin (50% inhibitory concentration [IC50], >100
      microM) yet was efficiently inhibited by two new FabH inhibitors, 5-chloro-4
      phenyl-[1,2]-dithiol-3-one (IC50, 1.87 +/- 0.10 microM) and 4-phenyl-5
      phenylimino-[1,2,4]dithiazolidin-3-one (IC50, 0.775 +/- 0.08 microM).

PMID- 11959562
TI  - Antimicrobial activity of quinupristin-dalfopristin combined with other
      antibiotics against vancomycin-resistant enterococci.
AB  - Interactions between quinupristin-dalfopristin and six other antimicrobials were
      examined by checkerboard arrays against 50 clinical isolates of vancomycin
      resistant Enterococcus faecium selected to represent a range of susceptibilities
      to individual agents. Unequivocal synergistic or antagonistic interactions at
      clinically relevant concentrations were infrequently encountered when the
      streptogramin was combined with chloramphenicol, ampicillin, imipenem,
      vancomycin, or teicoplanin. Combinations with doxycycline resulted in synergistic
      inhibition in 36% of checkerboards. Against 10 strains of Enterococcus faecalis,
      synergistic interactions were found when quinupristin-dalfopristin was combined
      with doxycycline (four strains), either glycopeptide (three strains), or
      ampicillin (two strains). Combination with quinupristin-dalfopristin increased
      the ampicillin MIC from 1 to 4 microg/ml for one strain. For 10 strains of E.
      faecium, interactions were also assessed by time-kill methods using
      concentrations of the agents attainable in human serum. Most of these
      antimicrobials augmented killing by quinupristin-dalfopristin to a minor degree.
      Against 2 of the 12 strains in this collection that were not highly resistant to
      gentamicin, the combination of quinupristin-dalfopristin (2 microg/ml) plus
      gentamicin (5 microg/ml) resulted in killing approaching 3 log(10) CFU/ml. With
      the exception of doxycycline, inhibitory interactions between quinupristin
      dalfopristin and other agents tested against vancomycin-resistant strains of E.
      faecium were uncommon at clinically relevant concentrations.

PMID- 11959563
TI  - Change in colony morphology of Candida lusitaniae in association with development
      of amphotericin B resistance.
AB  - It is not uncommon to see amphotericin B treatment failure in patients with
      systemic infection caused by Candida lusitaniae. We report a patient with stage
      IV ovarian carcinoma and C. lusitaniae sepsis whose treatment with amphotericin B
      failed. The initial blood isolate was susceptible to amphotericin B in vitro;
      however, the MIC for a blood isolate recovered 7 weeks after treatment began
      showed a fourfold increase. Direct subculture of two positive blood samples
      obtained within a week of the patient's death showed the coexistence of two
      distinct colony color variants on CHROMagar Candida (CAC). One variant was
      susceptible to amphotericin B, and one was resistant. These results emphasize the
      importance of repeat amphotericin B susceptibility testing for patients with
      persistent C. lusitaniae infection. The presence of colony variants on CAC may
      signal the emergence of amphotericin B resistance in C. lusitaniae and should be
      investigated.

PMID- 11959564
TI  - Characterization of wild-type and cidofovir-resistant strains of camelpox,
      cowpox, monkeypox, and vaccinia viruses.
AB  - Cidofovir ([(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] [HPMPC])
      resistant forms of camelpox, cowpox, monkeypox, and vaccinia viruses were
      developed by prolonged passage in Vero 76 cells in the presence of drug. Eight-
      to 27-fold-higher concentrations of cidofovir were required to inhibit the
      resistant viruses than were needed to inhibit the wild-type (WT) viruses.
      Resistant viruses were characterized by determining their cross-resistance to
      other antiviral compounds, examining their different replication abilities in two
      cell lines, studying the biochemical basis of their drug resistance, and
      assessing the degrees of their virulence in mice. These viruses were cross
      resistant to cyclic HPMPC and, with the exception of vaccinia virus, to (S)-1-(3
      hydroxy-2-phosphonylmethoxypropyl)adenine. Three of the four resistant cowpox and
      monkeypox viruses exhibited reduced abilities to infect and replicate in 3T3
      cells compared to their abilities in Vero 76 cells. Compared to the WT virus
      polymers the resistant cowpox virus DNA polymerase was 8.5-fold less sensitive to
      inhibition by cidofovir diphosphate, the active form of the drug. Intracellular
      phosphorylation of [3H]cidofovir was not stimulated or inhibited by infection
      with resistant cowpox virus. In intranasally infected BALB/c mice, WT cowpox
      virus was 80-fold more virulent than the resistant virus. Cidofovir treatment
      (100 mg/kg of body weight, given one time only as early as 5 min after virus
      challenge) of a resistant cowpox virus infection could not protect mice from
      mortality. However, the drug prevented mortality in 80 to 100% of the mice
      treated with a single 100-mg/kg dose at 1, 2, 3, or 4 days after WT virus
      challenge. By application of these results to human orthopoxvirus infections, it
      is anticipated that resistant viruses may be untreatable with cidofovir but their
      virulence may be attenuated. Studies will need to be conducted with cidofovir
      resistant monkeypox virus in monkeys to further support these hypotheses.

PMID- 11959565
TI  - Anti-human immunodeficiency virus interactions of SCH-C (SCH 351125), a CCR5
      antagonist, with other antiretroviral agents in vitro.
AB  - SCH-C (SCH 351125) is a small-molecule antagonist of the human immunodeficiency
      virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses
      with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. We have studied
      anti-HIV-1 interactions of SCH-C with other antiretroviral agents in vitro.
      Synergistic interactions were seen with nucleoside reverse transcriptase
      inhibitors (zidovudine and lamivudine), nonnucleoside reverse transcriptase
      inhibitors (efavirenz), and protease inhibitors (indinavir) at all inhibitory
      concentrations evaluated. We have also studied antiviral interactions between the
      HIV-1 fusion inhibitor T-20 and SCH-C against a panel of R5 HIV-1 isolates. We
      found synergistic interactions against all the viruses tested, some of which
      harbored resistance mutations to reverse transcriptase and protease inhibitors.
      Anti-HIV-1 synergy was also observed between SCH-C and another R5 virus
      inhibitor, aminooxypentane-RANTES. These findings suggest that SCH-C may be a
      useful anti-HIV drug in combination regimens and that a combination of chemokine
      coreceptor/fusion inhibitors may be useful in the treatment of multidrug
      resistant viruses.

PMID- 11959566
TI  - Effects of specific antibodies against Streptococcus pneumoniae on
      pharmacodynamic parameters of beta-lactams in a mouse sepsis model.
AB  - A dose-ranging study to investigate the in vivo effects of the presence of
      specific antibodies on the efficacy of beta-lactam treatment of sepsis caused by
      Streptococcus pneumoniae (non-beta-lactam-susceptible serotype 6B isolate) was
      performed with a BALB/c mouse model. Hyperimmune serum was obtained from mice
      immunized with the heat-inactivated strain. The rate of mortality was 100% in
      nontreated animals in the absence of specific antibodies. A single injection of a
      one-half or one-quarter dilution of hyperimmune serum produced 60 to 40% survival
      rates. In the absence of specific antibodies, the minimal effective doses of
      amoxicillin and cefotaxime that produced survival rates of 100 and 80% were 25
      and 50 mg/kg of body weight (three times a day for up to six doses),
      respectively. These doses produced times that the levels in serum remained above
      the MIC (deltaT > MICs) approximately 30% of the dosing interval. When specific
      antibodies were present (by administration of a one-half or one-quarter dilution
      of hyperimmune serum), the minimal effective doses of the antibiotics were 3.12
      and 6.25 mg/kg ( approximately 8 times lower), with the deltaT > MICs being
      approximately 3 and 5% of the dosing interval for amoxicillin and cefotaxime,
      respectively. This in vivo combined pharmacodynamic effect offers possibilities
      that can be used to address penicillin resistance.

PMID- 11959567
TI  - Pharmacodynamic activity and efficacy of linezolid in a rat model of pneumococcal
      pneumonia.
AB  - Linezolid is a new oxazolidinone antibiotic with potent activity against gram
      positive bacteria, including Streptococcus pneumoniae. The pharmacodynamic
      activity and in vivo efficacy of linezolid were compared to those of ceftriaxone
      in an immunocompetent rat model of pneumococcal pneumonia. Rats infected
      intratracheally with 8 x 10(7) CFU of a penicillin-sensitive (MIC, 0.032
      microg/ml) strain of S. pneumoniae were treated for 5 days beginning 18 h
      postinfection. Groups of rats were sham treated with oral phosphate-buffered
      saline or received oral liquid linezolid at 25 or 50 mg/kg of body weight twice a
      day (b.i.d.) or subcutaneous ceftriaxone at 100 mg/kg once daily. Mortality was
      monitored for 10 days postinfection; blood culturing was performed on day 1
      (pretreatment) and on days 3, 5, and 10 postinfection for the determination of
      bacteremia. Serum also was collected for the determination of pharmacokinetic and
      pharmacodynamic parameters at 30 min and at 3, 5, and 12 h (linezolid) or 3, 5,
      and 24 h (ceftriaxone) postdose. The cumulative mortality rates were 100% for the
      sham-treated group, 58.3% for the low-dose linezolid group, 8.3% for the high
      dose linezolid group, and 0% for the ceftriaxone group. Rats in each of the
      antibiotic treatment groups had significantly fewer bacteria (P < 0.00001) in
      their bronchoalveolar lavage fluid (BALF) on day 3 postinfection than sham
      treated rats. There also were significantly fewer organisms in the BALF of rats
      treated with ceftriaxone than in the BALF of rats treated with either dose of
      linezolid. Oral linezolid at 50 mg/kg b.i.d. therefore was as effective as
      ceftriaxone in experimental pneumococcal pneumonia, whereas the 25-mg/kg b.i.d.
      dose was significantly less effective. All pharmacodynamic parameters reflected
      efficacy and were significantly different for the two dosage regimens of
      linezolid (P < 0.01). However, the free-fraction pharmacodynamic parameters
      predictive of outcome were a value of >39% for the percentage of time in the
      experimental dosing interval during which the linezolid concentration exceeded
      the MIC and a value of >147 for the ratio of the area under the serum
      concentration-time curve to the MIC.

PMID- 11959568
TI  - In vitro and in vivo activities of posaconazole against Coccidioides immitis.
AB  - Posaconazole (SCH 56592) was tested against 25 strains of Coccidioides immitis to
      determine their in vitro susceptibilities. The geometric mean 48-h MIC of
      posaconazole (POSA) was 0.5 microg/ml, the MIC range was 0.25 to 1 microg/ml, and
      the MIC at which 50% of the isolates tested are inhibited (MIC50) and the MIC90
      were 0.5 and 1 microg/ml, respectively. The geometric mean 48-h MIC of
      itraconazole (ITRA) was 0.23 microg/ml, the MIC range was 0.125 to 0.5 microg/ml,
      and the MIC50 and MIC90 were both 0.25 microg/ml. Two strains of C. immitis were
      selected for in vivo studies on the basis of the POSA 48-h MICs for the isolates.
      POSA orally administered at 0.01, 0.1, 0.5, 1, 5, and 10 mg/kg of body weight/day
      was compared with ITRA administered at 10 and 30 mg/kg three times a day. The
      spleens and livers of mice that died or survived to day 50 were removed to
      measure the fungal burdens. Mice had >or=90% survival when they were treated with
      >or=0.5 mg of POSA per kg or 30 mg of ITRA per kg. Cultures of whole spleens and
      livers from mice treated with 10 mg of POSA per kg showed >or=70% sterilization.
      No sterilization of whole spleens and livers from mice treated with ITRA was
      seen. POSA displayed potent in vivo activity against the two strains of C.
      immitis tested.

PMID- 11959569
TI  - Pharmacokinetics of amino acid phosphoramidate monoesters of zidovudine in rats.
AB  - In vitro studies have demonstrated that water-soluble, nontoxic phosphoramidates
      of azidothymidine (zidovudine [AZT]) have significant and specific anti-human
      immunodeficiency virus and anticancer activity. Although polar, these compounds
      are internalized and processed to the corresponding nucleoside monophosphates.
      Eight methyl amide and methyl ester phosphoramidate monoesters composed of D- or
      L-phenylalanine or tryptophan and AZT were synthesized. The plasma stability and
      protein binding studies were carried out in vitro. Then in vivo pharmacokinetic
      evaluations of six of the compounds were conducted. Sprague-Dawley rats received
      each compound by intravenous bolus dose, and serial blood and urine samples were
      collected. AZT and phosphoramidate concentrations in plasma and urine were
      quantitated by high-performance liquid chromatography with UV or fluorescence
      detection. Pharmacokinetic parameters were calculated by standard
      noncompartmental means. The plasma half-lives of the phosphoramidates were 10- to
      20-fold longer than the half-life of AZT. Although the renal clearances of the
      phosphoramidates were similar to AZT, their total body clearances were
      significantly greater than that of AZT. The 3- to 15-fold-larger volume of
      distribution (Vss) for the phosphoramidates relative to AZT appeared to be
      dependent on the stereochemistry of the amino acid, with the largest values being
      associated with the L-amino acids. The increased Vss indicates a much greater
      tissue distribution of the phosphoramidate prodrugs than of AZT. Amino acid
      phosphoramidate monoesters of AZT have improved pharmacokinetic properties over
      AZT and significant potential as in vivo pronucleotides.

PMID- 11959570
TI  - Effect of telithromycin (HMR 3647) on polymorphonuclear neutrophil killing of
      Staphylococcus aureus in comparison with roxithromycin.
AB  - HMR 3647 (telithromycin), a new ketolide, is active on intracellular pathogens.
      It was previously demonstrated that it inhibits superoxide anion production in a
      time- and concentration-dependent manner, at concentrations which inhibit 50% of
      the control response of about 55 microg/ml (5 min) to 30 microg/ml (30 min);
      these values are similar to those obtained with roxithromycin, a classical
      erythromycin A derivative. Here we investigated whether these drugs modified the
      bactericidal activity of human polymorphonuclear neutrophils (PMN) on four
      strains of Staphylococcus aureus with different profiles of susceptibility to
      macrolides and ketolides. We found that the main factor involved in killing was
      the antibacterial potency of the drugs, although combinations of antibiotics with
      PMN were slightly more active than each component used alone against two of the
      four strains. In addition, high concentrations of the drugs, which impaired the
      PMN oxidative burst, did not impair PMN bactericidal activity. Likewise, some
      cytokines which enhance PMN oxidative metabolism did not modify PMN bactericidal
      activity in the presence or absence of macrolides or ketolides. These data
      suggest that oxygen-independent mechanisms contribute to the bactericidal
      activity of PMN on these strains of S. aureus. Both live and/or heat-killed
      bacteria impaired the uptake of telithromycin and roxithromycin (but not that of
      levofloxacin, a quinolone) in a concentration-dependent manner, owing to a
      modulation of PMN transductional systems involved in the activation of the
      macrolide carrier.

PMID- 11959571
TI  - PEPT1-mediated cefixime uptake into human intestinal epithelial cells is
      increased by Ca2+ channel blockers.
AB  - Ca2+ channel blockers like nifedipine have been shown to increase the oral
      bioavailability of beta-lactam antibiotics, such as cefixime, in humans. The
      molecular mode of action of Ca2+ channel blockers on beta-lactam absorption,
      however, has not yet been defined. Using the Caco-2 human intestinal epithelial
      cell line, we assessed whether alterations in intracellular free Ca2+ ion
      (Ca2+in) concentrations by Ca2+ channel blockers or by Ca2+ ionophores affect
      [14C]cefixime absorption. Reduction of Ca2+in levels by Ca2+ channel blockers
      (nifedipine, verapamil, diltiazem, or bepridil) at concentrations of 100 microM
      led to 35 to 50% increases in the cellular uptake of 1 mM [14C]cefixime.
      Increases in Ca2+in levels by Ca2+ ionophores, on the other hand, led to 40%
      reductions in [14C]cefixime absorption. Nifedipine increased the V(max) of
      cefixime transport by 67%, whereas the K(m) of cefixime transport remained
      unaffected. By measuring the pH in Caco-2 cells loaded with the pH-sensitive
      fluorescent dye 2',7'-bis(2-carboxyethyl)-5-(6)-carboxyfluorescein, we show that
      cefixime transport mediated by the intestinal H+-coupled peptide transporter
      PEPT1 leads to intracellular acidification. This acid load was reduced by
      nifedipine, although the Ca2+ channel blocker increased the level of H+ and
      cefixime cotransport. Increases in Ca2+in levels by ionomycin enhanced the
      decline in intracellular pH induced by cefixime alone, although ionomycin reduced
      the level of H+ and cefixime cotransport. In conclusion, our studies demonstrate
      that alterations of Ca2+in levels, e.g., by Ca2+ channel blockers, affect pH
      regulatory systems, such as apical Na+ and H+ exchange, and thereby alter the H+
      gradient that serves as the driving force for uptake of beta-lactams into
      intestinal epithelial cells.

PMID- 11959572
TI  - Nonparametric population pharmacokinetic analysis of amikacin in neonates,
      infants, and children.
AB  - The therapeutic and toxic effects of amikacin are known to depend on its
      concentration in plasma, but the pharmacokinetics of this drug in neonates,
      infants, and children and the influences of clinical and biological variables
      have been only partially assessed. Therapeutic drug monitoring data collected
      from 155 patients (49 neonates, 77 infants, and 29 children) receiving amikacin
      were analyzed by a nonparametric population-based approach, the nonparametric
      maximum-likelihood method. We assessed the effects of gestational and postnatal
      age, weight, Apgar score, and plasma creatinine and urea concentrations on
      pharmacokinetic parameters. There is no specific formulation of amikacin for
      neonates and infants. We therefore used an error model to account for errors due
      to dilution during preparation of the infusion. The covariates that reduced the
      variance of clearance from plasma and the volume of distribution by more than 10%
      were postnatal age (43 and 28%, respectively) and body weight (30.4 and 17.4%,
      respectively). The expected reduction of clearance was about 10% for the plasma
      creatinine concentration. The other covariates studied (Apgar scores, plasma urea
      concentration, gestational age, sex) were found to have little effect.
      Simulations showed that a smaller percentage of patients had a maximum
      concentration in plasma/MIC ratio greater than 8 with a regimen of 7.5 mg/kg of
      body weight twice daily than with a regimen of 15 mg/kg once a day for MICs of 1
      to 8 mg/liter.

PMID- 11959573
TI  - In vitro and in vivo antifungal activities of TAK-456, a novel oral triazole with
      a broad antifungal spectrum.
AB  - TAK-456 is a novel oral triazole compound with potent and broad-spectrum in vitro
      antifungal activity and strong in vivo efficacy against Candida albicans and
      Aspergillus fumigatus. TAK-456 inhibited sterol synthesis of C. albicans and A.
      fumigatus by 50% at 3 to 11 ng/ml. TAK-456 showed strong in vitro activity
      against clinical isolates of Candida spp., Aspergillus spp., and Cryptococcus
      neoformans, except for Candida glabrata. The MICs at which 90% of the isolates
      tested were inhibited byTAK-456, fluconazole, itraconazole, voriconazole, and
      amphotericin B were 0.25, 4, 0.5, 0.13, and 0.5 microg/ml, respectively, for
      clinical isolates of C. albicans and 1, >64, 0.5, 0.5, and 0.5 microg/ml,
      respectively, for clinical isolates of A. fumigatus. Therapeutic activities of
      TAK-456 and reference triazoles against systemic lethal infections caused by C.
      albicans and A. fumigatus in mice were investigated by orally administering drugs
      once daily for 5 days, and efficacies of the compounds were evaluated by the
      prolongation of survival. In normal mice, TAK-456 and fluconazole were effective
      against infection caused by fluconazole-susceptible C. albicans at a dose of 1
      mg/kg. In transiently neutropenic mice, therapeutic activity of TAK-456 at 1
      mg/kg of body weight against infection with the same strain was stronger than
      those at 1 mg/kg of fluconazole. TAK-456 was effective against infections with
      two strains of fluconazole-resistant C. albicans at a dose of 10 mg/kg. TAK-456
      also expressed activities similar to or higher than those of itraconazole against
      the infections caused by two strains of A. fumigatus in neutropenic mice at a
      dose of 10 mg/kg. These results suggest that TAK-456 is a promising candidate for
      development for the treatment of candidiasis and aspergillosis in humans.

PMID- 11959574
TI  - DPC 817: a cytidine nucleoside analog with activity against zidovudine- and
      lamivudine-resistant viral variants.
AB  - Highly active antiretroviral therapy (HAART) is the standard treatment for
      infection with the human immunodeficiency virus (HIV). HAART regimens consist of
      protease inhibitors or nonnucleoside reverse transcriptase inhibitors combined
      with two or more nucleoside reverse transcriptase inhibitors (NRTIs). DPC 817,
      2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (PSI 5582 D-D4FC) is a potent
      inhibitor of HIV type 1 replication in vitro. Importantly, DPC 817 retains
      activity against isolates harboring mutations in the reverse transcriptase gene
      that confer resistance to lamivudine (3TC) and zidovudine (AZT), which are
      frequent components of initial HAART regimens. DPC 817 combines this favorable
      resistance profile with rapid uptake and conversion to the active metabolite DPC
      817-triphosphate, which has an intracellular half-life of 13 to 17 h.
      Pharmacokinetics in the rhesus monkey suggest low clearance of parent DPC 817 and
      a plasma half-life longer than that of either AZT or 3TC. Together, these
      properties suggest that DPC 817 may be useful as a component of HAART regimens in
      individuals with resistance to older NRTI agents.

PMID- 11959575
TI  - Presence of a group II intron in a multiresistant Serratia marcescens strain that
      harbors three integrons and a novel gene fusion.
AB  - We analyzed the role of integrons in the dissemination of antibiotic resistance
      in a recent multiresistant clinical isolate, Serratia marcescens SCH88050909
      (SCH909). This isolate harbors three integrons, all on a 60-kb conjugative
      plasmid. By PCR, hybridization, and sequencing analyses, we found that integron 1
      has the dfrA1 and ant(3")-Ia cassettes. The first cassette in integron 2 contains
      the ant(2")-Ia gene, separated from its attC site (59-base element) by a 1,971-bp
      insert containing a group II intron; this intron codes for a putative maturase
      reverse transcriptase on the complementary strand and is the first such intron to
      be found associated with an integron. The attC site is followed by a novel
      aminoglycoside resistance gene, ant(3")-Ii-aac(6')-IId, which has been
      characterized for its bifunctional ANT(3")-I and AAC(6')-II activities. DNA
      sequence analysis of this fused cassette suggests that insertion and excision due
      to the integrase activity could have an important role in the evolution of
      aminoglycoside resistance genes. This gene is followed by an unknown open reading
      frame with a typical attC site and a partial cassette composed of the beginning
      of the bla(OXA-10) cassette interrupted by IS1. The sequence downstream of IS1
      revealed that the bla(OXA-10) cassette is incomplete and that the 3' conserved
      segment of this integron is absent. Integron 3 is in a Tn1696-like transposon
      with the aac(3)-Ia cassette followed by three unknown cassettes and ant(3")-Ia.
      The presence of the group II intron and the relationship of group II introns in
      eubacteria with mobile elements suggest a possible role of this element in events
      such as cassette formation and/or plasmid evolution.

PMID- 11959576
TI  - tcrB, a gene conferring transferable copper resistance in Enterococcus faecium:
      occurrence, transferability, and linkage to macrolide and glycopeptide
      resistance.
AB  - A newly discovered gene, designated tcrB, which is located on a conjugative
      plasmid conferring acquired copper resistance in Enterococcus faecium, was
      identified in an isolate from a pig. The tcrB gene encodes a putative protein
      belonging to the CPx-type ATPase family with homology (46%) to the CopB protein
      from Enterococcus hirae. The tcrB gene was found in E. faecium isolated from pigs
      (75%), broilers (34%), calves (16%), and humans (10%) but not in isolates from
      sheep. Resistant isolates, containing the tcrB gene, grew on brain heart infusion
      agar plates containing up to 28 mM CuSO4 compared to only 4 mM for the
      susceptible isolates. Copper resistance, and therefore the presence of the tcrB
      gene, was strongly correlated to macrolide and glycopeptide resistance in
      isolates from pigs, and the tcrB gene was shown to be located on the same
      conjugative plasmid as the genes responsible for resistance to these two
      antimicrobial agents. The frequent occurrence of this new copper resistance gene
      in isolates from pigs, where copper sulfate is being used in large amounts as
      feed additive, suggests that the use of copper has selected for resistance.

PMID- 11959577
TI  - High prevalence of KatG Ser315Thr substitution among isoniazid-resistant
      Mycobacterium tuberculosis clinical isolates from northwestern Russia, 1996 to
      2001.
AB  - A total of 204 isoniazid (INH)-resistant strains of Mycobacterium tuberculosis
      isolated from different patients in the northwestern region of Russia from 1996
      to 2001 were screened by a PCR-restriction fragment length polymorphism (RFLP)
      assay. This assay uses HapII cleavage of an amplified fragment of the katG gene
      to detect the transversion 315AGC-->ACC (Ser-->Thr), which is associated with INH
      resistance. This analysis revealed a 93.6% prevalence of the katG S315T mutation
      in strains from patients with both newly and previously diagnosed cases of
      tuberculosis (TB). This mutation was not found in any of 57 INH-susceptible
      isolates included in the study. The specificity of the assay was 100%; all
      isolates that contained the S315T mutation were classified as resistant by a
      culture-based susceptibility testing method. The Beijing genotype, defined by
      IS6110-RFLP analysis and the spacer oligonucleotide typing (spoligotyping)
      method, was found in 60.3% of the INH-resistant strains studied. The katG S315T
      shift was more prevalent among Beijing genotype strains than among non-Beijing
      genotype strains: 97.8 versus 84.6%, respectively, for all isolates, including
      those from patients with new and previously diagnosed cases, isolated from 1999
      to 2001 and 100.0 versus 86.5%, respectively, for isolates from patients with new
      cases isolated from 1996 to 2001. The design of this PCR-RFLP assay allows the
      rapid and unambiguous identification of the katG 315ACC mutant allele. The
      simplicity of the assay permits its implementation into routine practice in
      clinical microbiology laboratories in regions with a high incidence of TB where
      this mutation is predominant, including northwestern Russia.

PMID- 11959578
TI  - Pharmacodynamic assessment of clarithromycin in a murine model of pneumococcal
      pneumonia.
AB  - The pharmacodynamic profile of clarithromycin (CLR) was evaluated with a murine
      model of pneumonia. Eight Streptococcus pneumoniae isolates, including three
      macrolide-sensitive and five macrolide-resistant strains, were inoculated
      intratracheally into immunocompromised ICR mice as 10(8)-CFU bacterial
      suspensions. Orally administered CLR daily doses ranging from 5 to 600 mg/kg of
      body weight were given over 5 days, during which animal survival was monitored.
      The bacterial density in lung tissues was examined after 24 h of CLR treatment
      and in control groups. Pharmacokinetic analysis of CLR in mice demonstrated that
      the regimen of 150 mg/kg twice a day was representative of human pharmacokinetics
      and was used to compare the efficacy of CLR against sensitive and resistant S.
      pneumoniae strains. Immunocompetent CBA/J mice were also infected and treated as
      described above and evaluated for bacterial density and survival to assess the
      effect of the presence of leukocytes. All three pharmacodynamic parameters, the
      duration (percent) of the time that serum CLR concentrations remain above the MIC
      (%T>MIC), the ratio of the area under the concentration-time curve from 0 to 24 h
      (AUC(0-24)) to the MIC, and the ratio of the maximum concentration of drug in
      serum to the MIC, were found to be closely correlated to CLR bacterial efficacy
      (P < 0.001). Furthermore, all parameters had close correlation to bacterial
      density (r(2) = 0.72 to 0.82), median survival (r(2) = 0.93 to 0.94), and total
      percent survival (r(2) = 0.91 to 0.92). These in vivo data suggest that the
      bacterial activity of CLR is closely correlated with all three parameters over a
      wide range of exposures and, as a consequence of parameter interdependency, AUC(0
      24)/MIC is the most reasonable predictor of antibiotic efficacy. In this
      neutropenic pneumonia model, CLR was less efficacious against S. pneumoniae
      strains for which MICs were >or=4 microg/ml. However, the presence of leukocytes
      in the immunocompetent mice resulted in improved bactericidal activity, relative
      to that in the neutropenic animals, despite an MIC of 4 microg/ml.

PMID- 11959579
TI  - Effects of metronidazole, tetracycline, and bismuth-metronidazole-tetracycline
      triple therapy in the Helicobacter pylori SS1 mouse model after 1 day of dosing:
      development of an H. pylori lead selection model.
AB  - We evaluated the effect of optimized doses and dosing schedules of metronidazole,
      tetracycline, and bismuth-metronidazole-tetracycline (BMT) triple therapy with
      only 1 day of dosing on Helicobacter pylori SS1 titers in a mouse model. A
      reduction of bacterial titers was observable with 22.5 and 112.5 mg of
      metronidazole per kg of body weight (as well as BMT) given twice daily and four
      times daily (QID). Two hundred milligrams of tetracycline per kilogram, given
      QID, resulted in only a slight reduction of H. pylori titers in the stomach. We
      argue that optimization of doses based on antimicrobial drug levels in the animal
      and shortened (1 or 2 days) drug administration can be used to facilitate early
      evaluation of putative anti-H. pylori drug candidates in lieu of using human
      doses and extended schedules (7 to 14 days), as can be deduced from the results
      seen with these antimicrobial agents.

PMID- 11959580
TI  - In vitro Plasmodium falciparum drug sensitivity assay: inhibition of parasite
      growth by incorporation of stomatocytogenic amphiphiles into the erythrocyte
      membrane.
AB  - Lupeol, which shows in vitro inhibitory activity against Plasmodium falciparum
      3D7 strain with a 50% inhibitory concentration (IC50) of 27.7 +/- 0.5 microM, was
      shown to cause a transformation of the human erythrocyte shape toward that of
      stomatocytes. Good correlation between the IC50 value and the membrane curvature
      changes caused by lupeol was observed. Preincubation of erythrocytes with lupeol,
      followed by extensive washing, made the cells unsuitable for parasite growth,
      suggesting that the compound incorporates into erythrocyte membrane irreversibly.
      On the other hand, lupeol-treated parasite culture continued to grow well in
      untreated erythrocytes. Thus, the antiplasmodial activity of lupeol appears to be
      indirect, being due to stomatocytic transformation of the host cell membrane and
      not to toxic effects via action on a drug target within the parasite. A number of
      amphiphiles that cause stomatocyte formation, but not those causing echinocyte
      formation, were shown to inhibit growth of the parasites, apparently via a
      mechanism similar to that of lupeol. Since antiplasmodial agents that inhibit
      parasite growth through erythrocyte membrane modifications must be regarded as
      unsuitable as leads for development of new antimalarial drugs, care must be
      exercised in the interpretation of results of screening of plant extracts and
      natural product libraries by an in vitro Plasmodium toxicity assay.

PMID- 11959581
TI  - A chemically modified tetracycline (CMT-3) is a new antifungal agent.
AB  - Several chemically modified tetracycline analogs (CMTs), which were chemically
      modified to eliminate their antibacterial efficacy, were unexpectedly found to
      have antifungal properties. Of 10 CMTs screened in vitro, all exhibited
      antifungal activities, although their efficacies varied. Among these compounds,
      CMT-315, -3, and -308 were found to be the most potent as antifungal agents. The
      MICs of CMT-3 against 47 strains of fungi in vitro were determined by using
      amphotericin B (AMB) and doxycycline as positive and negative controls,
      respectively. The MICs of CMT-3 were generally found to be between 0.25 and 8.00
      microg/ml, a range that approximates the blood levels of this drug when
      administrated orally to humans. Of all the yeast species tested to date, Candida
      albicans showed the greatest sensitivity to CMT-3. The filamentous species most
      susceptible to CMT-3 were found to be Epidermophyton floccosum, Microsporum
      gypseum, Pseudallescheria boydii, a Penicillium sp., Scedosporium apiospermum, a
      Tricothecium sp., and Trichophyton rubrum. Growth inhibition of C. albicans by
      CMT-3, determined by a turbidity assay, indicated a 50% inhibitory concentration
      of 1 microg/ml. Thirty-nine strains, including 20 yeasts and 19 molds, were used
      to measure viability (the ability to grow after treatment with a drug) inhibition
      by CMT-3 and AMB. CMT-3 exhibited fungicidal activity against most of these
      fungi, especially the filamentous fungi. Eighty-four percent (16 of 19) of the
      filamentous fungi tested showed more than 90% inhibition of viability by CMT-3.
      In contrast, AMB showed fungicidal activity against all yeasts tested. However,
      most of the filamentous fungi (16 of 19) showed less than 50% inhibition of
      viability by AMB, indicating that AMB is fungistatic against most of these
      filamentous fungi. To begin to identify the sites in fungal cells affected by CMT
      3, C. albicans and a Penicillium sp. were incubated with the compound at 35
      degrees C, and then the fluorescence of CMT-3 was observed by confocal laser
      scanning electron microscopy. CMT-3 appeared to have widespread intracellular
      distribution throughout C. albicans and the Penicillium sp. The mechanisms of the
      antifungal activity of CMT-3 are now being explored.

PMID- 11959582
TI  - Potato dextrose agar antifungal susceptibility testing for yeasts and molds:
      evaluation of phosphate effect on antifungal activity of CMT-3.
AB  - The broth macrodilution method (BMM) for antifungal susceptibility testing,
      approved by the National Committee for Clinical Laboratory Standards (NCCLS), was
      found to have deficiencies in testing of the antifungal activity of a new type of
      antifungal agent, a nonantibacterial chemically modified tetracycline (CMT-3).
      The high content of phosphate in the medium was found to greatly increase the
      MICs of CMT-3. To avoid the interference of phosphate in the test, a new method
      using potato dextrose agar (PDA) as a culture medium was developed. Eight strains
      of fungi, including five American Type Culture Collection strains and three
      clinical isolates, were used to determine the MICs of amphotericin B and
      itraconazole with both the BMM and the PDA methods. The MICs of the two
      antifungal agents determined with the PDA method showed 99% agreement with those
      determined with the BMM method within 1 log(2) dilution. Similarly, the overall
      reproducibility of the MICs with the PDA method was above 97%. Three other
      antifungal agents, fluconazole, ketoconazole, and CMT-3, were also tested in
      parallel against yeasts and molds with both the BMM and the PDA methods. The MICs
      of fluconazole and ketoconazole determined with the PDA method showed 100%
      agreement within 1 log(2) dilution of those obtained with the BMM method.
      However, the MICs of CMT-3 determined with the BMM method were as high as 128
      times those determined with the PDA method. The effect of phosphate on the
      antifungal activity of CMT-3 was evaluated by adding Na2HPO4 to PDA in the new
      method. It was found that the MIC of CMT-3 against a Penicillium sp. increased
      from 0.5 microg/ml (control) to 2.0 microg/ml when the added phosphate was used
      at a concentration of 0.8 mg/ml, indicating a strong interference of Na2HPO4 with
      the antifungal activity of CMT-3. Except for fluconazole, all the other
      antifungal agents demonstrated clear end points among the yeasts and molds
      tested. Nevertheless, with its high reproducibility, good agreement with NCCLS
      proposed MIC ranges, and lack of interference of phosphate, the PDA method shows
      promise as a useful assay for antifungal susceptibility testing and screening for
      new antifungal agents, especially for drugs that may be affected by high
      (supraphysiologic) phosphate concentrations.

PMID- 11959583
TI  - Plasmidic extended-spectrum beta-lactamases in Vibrio cholerae O1 El Tor isolates
      in Argentina.
AB  - Since 1992 there have been seven major outbreaks of cholera in Argentina.
      Susceptibility analysis of 1,947 isolates (40% of reported cases) of Vibrio
      cholerae O1 biotype El Tor suggested the presence of extended-spectrum beta
      lactamases (ESBLs) in 28 isolates. Because of their different susceptibility
      profiles, V. cholerae isolates M1502, M1516, M1573, and M3030 (all of which are
      of the Ogawa serotype) were selected for the present study. By susceptibility
      analysis, isoelectric focusing, and PCR-based restriction fragment length
      polymorphism analysis, CTX-M-type enzymes were identified in three isolates,
      whereas a PER-2-type enzyme, in addition to a TEM-1-like enzyme, was identified
      in the other isolate. The presence of these ESBLs in V. cholerae isolates
      resulted in MICs well below those commonly observed for members of the family
      ENTEROBACTERIACEAE: Genes that encode both ESBLs were transferred to Escherichia
      coli by conjugation, together with all determinants of resistance to non-beta
      lactam antibiotics (gentamicin, kanamycin, and sulfamethoxazole for all isolates;
      amikacin and streptomycin for three isolates; trimethoprim, tetracycline, and
      chloramphenicol for two isolates). Plasmid profile analysis and Southern blotting
      revealed the presence of single plasmids of about 150 kb in the four V. cholerae
      isolates and their respective transconjugants and revealed that the plasmids
      harbored genes encoding CTX-M-type or PER-2-type ESBLs. These results strongly
      suggest the broad spread of these ESBLs among genera belong to families other
      than the ENTEROBACTERIACEAE:

PMID- 11959584
TI  - Interactions between biocide cationic agents and bacterial biofilms.
AB  - The resistance of bacterial biofilms to physical and chemical agents is
      attributed in the literature to various interconnected processes. The limitation
      of mass transfer alters the growth rate, and physiological changes in the
      bacteria in the film also appear. The present work describes an approach to
      determination of the mechanisms involved in the resistance of bacteria to
      quaternary ammonium compounds (benzalkonium chloride) according to the C-chain
      lengths of those compounds. For Pseudomonas aeruginosa CIP A 22, the level of
      resistance of the bacteria in the biofilm relative to that of planktonic bacteria
      increased with the C-chain length. For cells within the biofilm, the
      exopolysaccharide induced a characteristic increase in surface hydrophilicity.
      However, this hydrophilicity was eliminated by simple resuspension and washing.
      The sensitivity to quaternary ammonium compounds was restored to over 90%.
      Staphylococcus aureus CIP 53 154 had a very high level of resistance when it was
      in the biofilm form. A characteristic of bacteria from the biofilm was a
      reduction in the percent hydrophobicity, but the essential point is that this
      hydrophobicity was retained after the biofilm bacteria were resuspended and
      washed. The recovery of sensitivity was thus only partial. These results indicate
      that the factors involved in biofilm resistance to quaternary ammonium compounds
      vary according to the bacterial modifications induced by the formation of a
      biofilm. In the case of P. aeruginosa, we have underlined the involvement of the
      exopolysaccharide and particularly the three-dimensional structure (water
      channels). In the case of S. aureus, the role of the three-dimensional structure
      is limited and drastic physiological changes in the biofilm cells are more highly
      implicated in resistance.

PMID- 11959585
TI  - Intrapulmonary pharmacokinetics of linezolid.
AB  - In this study, our objective was to determine the steady-state intrapulmonary
      concentrations and pharmacokinetic parameters of orally administered linezolid in
      healthy volunteers. Linezolid (600 mg every 12 h for a total of five doses) was
      administered orally to 25 healthy adult male subjects. Each subgroup contained
      five subjects, who underwent bronchoscopy and bronchoalveolar lavage (BAL) 4, 8,
      12, 24, or 48 h after administration of the last dose. Blood was obtained for
      drug assay prior to administration of the first dose and fifth dose and at the
      completion of bronchoscopy and BAL. Standardized bronchoscopy was performed
      without systemic sedation. The volume of epithelial lining fluid (ELF) recovered
      was calculated by the urea dilution method, and the total number of alveolar
      cells (AC) was counted in a hemocytometer after cytocentrifugation. Linezolid was
      measured in plasma by a high-pressure liquid chromatography (HPLC) technique and
      in BAL specimens and AC by a combined HPLC-mass spectrometry technique. Areas
      under the concentration-time curves (AUCs) for linezolid in plasma, ELF, and AC
      were derived by noncompartmental analysis. Half-lives for linezolid in plasma,
      ELF, and AC were calculated from the elimination rate constants derived from a
      monoexponential fit of the means of the observed concentrations at each time
      point. Concentrations (means +/- standard deviations) in plasma, ELF, and AC,
      respectively, were 7.3 +/- 4.9, 64.3 +/- 33.1, and 2.2 +/- 0.6 microg/ml at the 4
      h BAL time point and 7.6 +/- 1.7, 24.3 +/- 13.3, and 1.4 +/- 1.3 microg/ml at the
      12-h BAL time point. Linezolid concentrations in plasma, ELF, and AC declined
      monoexponentially, with half-lives of 6.9, 7.0, and 5.7 h, respectively. For a
      MIC of 4, the 12-h plasma AUC/MIC and maximum concentration/MIC ratios were 34.6
      and 3.9, respectively, and the percentage of time the drug remained above the MIC
      for the 12-h dosing interval was 100%; the corresponding ratios in ELF were 120
      and 16.1, respectively, and the percentage of time the drug remained above the
      MIC was 100%. The long plasma and intrapulmonary linezolid half-lives and the
      percentage of time spent above the MIC of 100% of the dosing interval provide a
      pharmacokinetic rationale for drug administration every 12 h and indicate that
      linezolid is likely to be an effective agent for the treatment of pulmonary
      infections.

PMID- 11959586
TI  - Bloodstream infections by extended-spectrum beta-lactamase-producing Escherichia
      coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome.
AB  - To determine the epidemiologic features and clinical outcomes of bloodstream
      infections caused by extended-spectrum beta-lactamase (ESBL)-producing
      Escherichia coli and Klebsiella pneumoniae isolates, cases of bacteremia caused
      by these organisms in children were analyzed retrospectively. Among the 157 blood
      isolates recovered from 1993 to 1998 at the Seoul National University Children's
      Hospital, the prevalence of ESBL production was 17.9% among the E. coli isolates
      and 52.9% among the K. pneumoniae isolates. The commonest ESBLs were SHV-2a and
      TEM-52. A novel ESBL, TEM-88, was identified. Pulsed-field gel electrophoresis
      analysis of the ESBL-producing organisms showed extensive diversity in clonality.
      The medical records of 142 episodes were reviewed. The risk factors for
      bloodstream infection with ESBL-producing organisms were prior hospitalization,
      prior use of oxyimino-cephalosporins, and admission to an intensive care unit
      within the previous month. There was no difference in clinical severity between
      patients infected with ESBL-producing strains (the ESBL group) and those infected
      with ESBL-nonproducing strains (the non-ESBL group) at the time of presentation.
      However, the overall fatality rate for the ESBL group was significantly higher
      than that for the non-ESBL group: 12 of 45 (26.7%) versus 5 of 87 (5.7%) (P =
      0.001). In a subset analysis of patients treated with extended-spectrum
      cephalosporins with or without an aminoglycoside, favorable response rates were
      significantly higher in the non-ESBL group at the 3rd day (6 of 17 versus 33 of
      51; P = 0.035), the 5th day (6 of 17 versus 36 of 50; P < 0.05), and the end of
      therapy (9 of 17 versus 47 of 50; P < 0.001). In conclusion, the ESBL production
      of the infecting organisms has a significant impact on the clinical course and
      survival of pediatric patients with bacteremia caused by E. coli and K.
      pneumoniae.

PMID- 11959587
TI  - Accessory gene regulator (agr) locus in geographically diverse Staphylococcus
      aureus isolates with reduced susceptibility to vancomycin.
AB  - The majority of infections with glycopeptide intermediate-level resistant
      Staphylococcus aureus (GISA) originate in biomedical devices, suggesting a
      possible increased ability of these strains to produce biofilm. Loss of function
      of the accessory gene regulator (agr) of S. aureus has been suggested to confer
      an enhanced ability to bind to polystyrene. We studied agr in GISA, hetero-GISA,
      and related glycopeptide-susceptible S. aureus isolates. All GISA strains from
      diverse geographic origins belong to agr group II. All GISA strains were
      defective in agr function, as demonstrated by their inability to produce delta
      hemolysin. Hetero-GISA isolate A5940 demonstrated a nonsense mutation in agrA
      that was not present in a pulsed-field gel electrophoresis-indistinguishable
      vancomycin-susceptible isolate from the same patient. Various other agr point
      mutations were noted in several clinical GISA and hetero-GISA isolates. A
      laboratory-generated agr-null strain demonstrated a small but reproducible
      increase in vancomycin heteroresistance after growth in vitro in subinhibitory
      concentrations of vancomycin. This was not seen in the isogenic agr group II
      parent strain in which agr was intact. The in vitro bactericidal activity of
      vancomycin was attenuated in the agr-null strain compared to the parent strain.
      These findings imply that compromised agr function is advantageous to clinical
      isolates of S. aureus toward the development of vancomycin heteroresistance,
      perhaps through the development of vancomycin tolerance.

PMID- 11959589
TI  - In vitro interactions of artemisinin with atovaquone, quinine, and mefloquine
      against Plasmodium falciparum.
AB  - The interactions of artemisinin with atovaquone, quinine, and mefloquine were
      investigated in three Plasmodium falciparum strains (strains F-32, FCR-3, and K
      1) by an in vitro culture assay. The parasites were cultured for 48 h in the
      presence of different concentrations and proportions of two drugs at a time in a
      checkerboard design. The response parameters were determined, and the sums of the
      fractional inhibitory concentrations (sigmaFICs) of the drug combinations were
      calculated for different degrees of inhibition (50% effective concentration
      [EC50], EC90, and EC99). Within therapeutically relevant molar ratios (19 to
      200), the combination of quinine and artemisinin showed mean sigmaFICs of 1.71 at
      the EC50, 0.36 at the EC90, and 0.13 at the EC99, indicating increasing
      synergism. Within the range of molar ratios of 4.3 to 50, the combination of
      mefloquine and artemisinin yielded mean sigmaFCIs of 0.93, 0.44, and 0.31 at the
      EC50, EC90, and EC99, respectively, indicating synergism. The atovaquone
      combination showed additive activity to synergism at atovaquone/artemisinin
      proportions considered relevant to the in vivo situation, i.e., between 4.3 and
      200, with the mean sigmaFICs decreasing from 1.34 at the EC50 to 0.85 and 0.23 at
      the EC90 and EC99, respectively. Interstrain differences in the degree of drug
      interaction were seen with the three strains for all combinations. Synergism was
      most consistent with quinine.

PMID- 11959588
TI  - Comparison of levofloxacin, alatrofloxacin, and vancomycin for prophylaxis and
      treatment of experimental foreign-body-associated infection by methicillin
      resistant Staphylococcus aureus.
AB  - The prophylactic and therapeutic activities of two fluoroquinolones, levofloxacin
      and alatrofloxacin (the L-Ala-L-Ala prodrug of trovafloxacin), were compared to
      those of vancomycin in two different experimental models of foreign-body
      associated infections caused by methicillin-resistant but quinolone-susceptible
      Staphylococcus aureus (MRSA) isolates. In a guinea pig model of prophylaxis,
      subcutaneously implanted tissue cages were infected with 10(3) CFU of MRSA, which
      was a 100% infectious dose in control animals. A single dose of 50 mg of
      levofloxacin per kg of body weight, administered intraperitoneally 3 h before
      bacterial challenge, was more efficient than vancomycin for the prevention of
      infections in tissue cages with MRSA inocula of 10(4) and 10(5) CFU. In a rat
      model used to evaluate therapy of chronic tissue cage infection caused by MRSA,
      the efficacies of 7-day high-dose regimens of levofloxacin (100 mg/kg once a day
      [q.d.] or 50 mg/kg twice a day [b.i.d.]) or alatrofloxacin (50 mg/kg q.d.) were
      compared to the efficacy of vancomycin (50 mg/kg b.i.d.). Active levels of
      levofloxacin, trovafloxacin, and vancomycin were continuously present in tissue
      cage fluid, with the levels exceeding the minimal bactericidal concentrations for
      MRSA during therapy. The q.d. and b.i.d. regimens of levofloxacin had equivalent
      activities and were significantly (P < 0.05) more active than alatrofloxacin or
      vancomycin in decreasing the viable counts of MRSA in tissue cage fluids. No
      quinolone-resistant mutants emerged during therapy with either fluoroquinolone.
      The mechanisms explaining the inferior activity of alatrofloxacin compared to the
      activity of levofloxacin against chronic foreign-body-associated infections by
      MRSA are unknown.

PMID- 11959590
TI  - Antagonism between aminoglycosides and beta-lactams in a methicillin-resistant
      Staphylococcus aureus isolate involves induction of an aminoglycoside-modifying
      enzyme.
AB  - We encountered three clinical isolates of methicillin-resistant Staphylococcus
      aureus which were susceptible to netilmicin and arbekacin in the absence of beta
      lactam antibiotics but which were resistant to them in the presence of beta
      lactam antibiotics. One of these strains, KU5801, was used to further investigate
      the antagonism between aminoglycosides and beta-lactam antibiotics. beta-Lactam
      antibiotics induced bacterial synthesis of aminoglycoside-6'-N-acetyltransferase
      and 2"-O-phosphotransferase [AAC(6')-APH(2")] in association with decreased
      antimicrobial activities of aminoglycosides. A 14.4-kb EcoRI fragment that
      included the genes that control for beta-lactam-inducible aminoglycoside
      resistance was cloned from a 31-kb conjugative plasmid present in KU5801.
      Restriction fragment mapping and PCR analysis suggested that a Tn4001-like
      element containing a gene encoding AAC(6')-APH(2") was located downstream from a
      truncated blaZ gene. The DNA sequence between blaR1 and a Tn4001-like element was
      determined. The Tn4001-IS257 hybrid structure was cointegrated into the blaZ
      gene, and the typical sequences for the termination of transcription were not
      found between these regions. We deduced that antagonism of aminoglycosides by
      beta-lactam antibiotics in isolate KU5801 involved transcription of the aac(6')
      Ie-aph(2")-Ia gene under the influence of the system regulating penicillinase
      production.

PMID- 11959592
TI  - Crystal structure of (-)-mefloquine hydrochloride reveals consistency of
      configuration with biological activity.
AB  - The absolute configuration of (-)-mefloquine has been established as 11R,12S by X
      ray crystallography of the hydrochloride salt, thus allowing comparison of the
      configuration of mefloquine's optical isomers to those of quinine and quinidine.
      (-)-Mefloquine has the same stereochemistry as quinine, and (+)-mefloquine has
      the same stereochemistry as quinidine. Since (+)-mefloquine is more potent than (
      )-mefloquine in vitro against the D6 and W2 strains of Plasmodium falciparum and
      quinidine is more potent than quinine, a common stereochemical component for
      antimalarial activity is implicated. The crystal of (-)-mefloquine hydrochloride
      contained four different conformations which mainly differ in a small rotation of
      the piperidine ring. These conformations are essentially the same as the
      crystalline conformations of racemic mefloquine methylsulfonate monohydrate,
      mefloquine hydrochloride, and mefloquine free base. The crystallographic
      parameters for (-)-mefloquine hydrochloride hydrate were as follows: C17H17F
      (6)N(2)O(+)Cl(-) .0.25 H2O; M(r), 419.3; symmetry of unit cell, orthorhombic;
      space group, P2(1)2(1)2(1); parameters of unit cell, a = 12.6890 +/- 0.0006 A (1
      A = 0.1 nm), b = 18.9720 +/- 0.0009 A, c = 32.189 +/- 0.017 A; volume of unit
      cell, 7,749 +/- 4 A(3); number of molecules per unit cell, 16; calculated
      density, 1.44 g cm(-3); source of radiation, Cu Kalpha (lambda = 1.54178 A); mu
      (absorption coefficient), 2.373 mm(-1); room temperature was used; final R(1)
      (residual index), 0.0874 for 3,692 reflections with intensities greater than
      2sigma. All of the hydroxyl and amine hydrogen atoms participate in
      intermolecular hydrogen bonds with chloride ions. The orientation of the amine
      and hydroxyl groups in (+)-mefloquine may define the optimal geometry for
      hydrogen bonding with cellular constituents.

PMID- 11959591
TI  - Shiga-like toxin II derived from Escherichia coli O157:H7 modifies renal handling
      of levofloxacin in rats.
AB  - The effect of Shiga-like toxin II (SLT-II) (2 microg/animal), which was derived
      from Escherichia coli O157:H7, on renal handling of levofloxacin (LVX), a model
      drug for quinolone antimicrobial agents, was investigated in rats 24 h after
      intravenous injection. In histopathological examination, acute tubular injury was
      observed in SLT-II-treated rats, but the glomeruli were not injured. SLT-II
      significantly increased the steady-state concentration of LVX in plasma to 1.5
      fold that of control rats. SLT-II induced significant decreases in the glomerular
      filtration rate (GFR) and renal clearance (CL(R)) of LVX. SLT-II slightly, but
      significantly, increased the unbound fraction and decreased renal plasma flow
      with no change in the extraction ratio of p-aminohippurate. SLT-II significantly
      increased concentrations of tumor necrosis factor alpha (TNF-alpha) and nitrite
      and nitrate (NOx) in plasma. The TNF-alpha inhibitor pentoxifylline partly, but
      significantly, inhibited SLT-II-induced decreases in the GFR and CL(R) of LVX; in
      contrast, S-methylisothiourea, a selective inhibitor of inducible nitric oxide
      synthase, did not. Western blotting analysis revealed that SLT-II did not alter
      the levels of multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein
      in kidneys 24 h after injection, assuming the lack of involvement of Mrp2 and P
      glycoprotein in SLT-II-induced acute renal tubular injury and renal handling of
      LVX observed 24 h after SLT-II injection. The present study suggests that SLT-II
      impairs the renal handling of LVX by decreasing GFR and causing decreased renal
      plasma flow.

PMID- 11959593
TI  - Chromosomal system for studying AmpC-mediated beta-lactam resistance mutation in
      Escherichia coli.
AB  - In some enterobacterial pathogens, but not in Escherichia coli, loss-of-function
      mutations in the ampD gene are a common route to beta-lactam antibiotic
      resistance. We constructed an assay system for studying mechanism(s) of
      enterobacterial ampD mutation using the well-developed genetics of E. coli. We
      integrated the Enterobacter ampRC genes into the E. coli chromosome. These cells
      acquire spontaneous recombination- and SOS response-independent beta-lactam
      resistance mutations in ampD. This chromosomal system is useful for studying
      mutation mechanisms that promote antibiotic resistance.

PMID- 11959594
TI  - Effects of specific zidovudine resistance mutations and substrate structure on
      nucleotide-dependent primer unblocking by human immunodeficiency virus type 1
      reverse transcriptase.
AB  - Nucleotide-dependent unblocking of chain-terminated DNA by human immunodeficiency
      virus type 1 reverse transcriptase (RT) is enhanced by the presence of mutations
      associated with 3'-azido-3'-deoxythymidine (AZT) resistance. The increase in
      unblocking activity was greater for mutant combinations associated with higher
      levels of in vivo AZT resistance. The difference between mutant and wild-type
      activity was further enhanced by introduction of a methyl group into the
      nucleotide substrate and was decreased for a nonaromatic substrate, suggesting
      that pi-pi interactions between RT and an aromatic structure may be facilitated
      by these mutations.

PMID- 11959595
TI  - 30S ribosomal subunit assembly is a target for inhibition by aminoglycosides in
      Escherichia coli.
AB  - The aminoglycosides paromomycin and neomycin were examined in Escherichia coli
      cells for an inhibitory effect on 30S ribosomal subunit assembly. Both compounds
      inhibited the growth rate, viable cell number, and protein synthesis rate with
      similar 50% inhibitory concentrations. Each drug also showed a concentration
      dependent inhibition of 30S subunit formation. The inhibitory effect on 30S
      particle formation was approximately equivalent to the inhibitory effect on
      translation for these antibiotics.

PMID- 11959596
TI  - New Mg2+-dependent oxytetracycline resistance determinant tet 34 in Vibrio
      isolates from marine fish intestinal contents.
AB  - A new oxytetracycline (OTC) resistance (Otc(r)) determinant, Tet 34, was cloned
      from chromosomal DNA of Vibrio sp. no. 6 isolated from intestinal contents of
      cultured yellowtail (Seriola quinqueradiata). The transformant, containing cloned
      Tet 34, could grow in broth containing 25 microg of drug per ml with 10 mM MgCl2.
      Tet 34 encoded an open reading frame (ORF) 154 amino acids long. The amino acid
      sequence of the ORF was homologous to sequences of several bacterial xanthine
      guanine phosphoribosyltransferases (XPRTs), which act in purine nucleotide
      salvage synthesis. Mg2+ binding site residues and the active site were highly
      conserved in XPRT and the ORF of Tet 34. The results suggest that Tet 34 encodes
      a new Mg2+-dependent Otc(r) mechanism.

PMID- 11959597
TI  - Activities of new fluoroquinolones, ketolides, and other antimicrobials against
      blood culture isolates of viridans group streptococci from across Canada, 2000.
AB  - The rates of nonsusceptibility to penicillin, erythromycin, and clindamycin of
      191 blood culture isolates of viridans group streptococci collected from across
      Canada in 2000 were 36, 42, and 10%, respectively. Although 8% of the strains
      were resistant to ciprofloxacin (MIC >or= 4 microg/ml), the MICs of gemifloxacin,
      BMS 284756, telithromycin, and ABT 773 at which 90% of the strains were inhibited
      were 0.06, 0.06, 0.12, and 0.03 microg/ml, respectively.

PMID- 11959598
TI  - Pharmacokinetics of piperacillin-tazobactam in anuric intensive care patients
      during continuous venovenous hemodialysis.
AB  - The pharmacokinetics of piperacillin-tazobactam were investigated in eight anuric
      intensive care patients treated by continuous venovenous hemodialysis (CVVHD).
      The elimination half-life of piperacillin was 4.3 +/- 1.2 h, and that of
      tazobactam was 5.6 +/- 1.3 h. The contribution of CVVHD to the overall
      elimination was relevant (>25%) for both drugs.

PMID- 11959599
TI  - Comparative pharmacodynamics of three newer fluoroquinolones versus six strains
      of staphylococci in an in vitro model under aerobic and anaerobic conditions.
AB  - Six strains of staphylococci were exposed to levofloxacin, moxifloxacin, or
      trovafloxacin in an in vitro pharmacodynamic model under both aerobic and
      anaerobic conditions. Each agent demonstrated a rapid 3-log(10) kill versus
      susceptible isolates regardless of condition. Against clinical isolates with
      reduced susceptibility, regrowth occurred by 24 h and was frequently associated
      with further increases in MICs.

PMID- 11959600
TI  - Association of metronidazole resistance and natural competence in Helicobacter
      pylori.
AB  - To study whether the capability of horizontal DNA transfer is associated with
      metronidazole resistance in Helicobacter pylori, a total of 81 clinical isolates
      were tested for MICs of metronidazole (MTZ). The MIC assays were performed by
      using the E-test and reconfirmed by the agar dilution method. Natural competence
      assays were performed by transferring a chloramphenicol acetyltransferase
      cassette and a 23S rRNA gene from a clarithromycin-resistant strain (with an A-to
      G mutation at nucleotide 2143) by using natural transformation. Of the 81
      isolates, 65 (80.2%) were naturally competent while 16 were not. Among the 65
      naturally competent strains, 39 (60%) were highly resistant to MTZ (MICs, >32
      microg/ml) while only 2 of 16 (12.5%) noncompetent strains were highly MTZ
      resistant (P, <0.001). Therefore, there is an association between natural
      competence and MTZ resistance.

PMID- 11959601
TI  - Lack of interaction of fluoroquinolones with lipopolysaccharides.
AB  - Fluoroquinolones are known to chelate with di- and trivalent cations, and it has
      accordingly been claimed that they perturb the integrity of the outer membrane
      (OM) of gram-negative bacteria. So far, chelation has not been assessed in
      biologically relevant test systems. Therefore, we investigated the interaction of
      ciprofloxacin and moxifloxacin in the absence and presence of Mg2+ with whole
      bacteria and isolated lipopolysaccharide (LPS) from various rough mutant strains
      of Salmonella enterica chemotypes by applying different biophysical techniques.
      We found that the fluoroquinolones did not disturb the integrity of the OM and
      neither were incorporated into LPS monolayers nor displaced Ca2+ from LPS
      monolayers, suggesting that chelation of fluoroquinolones with divalent cations
      does not contribute to the antibacterial effect of fluoroquinolones.

PMID- 11959602
TI  - rpoB mutation conferring rifampin resistance in Streptococcus pyogenes.
AB  - Streptococcus pyogenes BM4478 and Staphylococcus aureus BM4479 were isolated from
      a patient undergoing rifampin therapy. High-level resistance to rifampin was due
      to the following mutations in the rpoB gene: Ser522Leu in strain BM4478 and
      His526Asn and Ser574Leu in strain BM4479.

PMID- 11959603
TI  - Macrolide and tetracycline resistance and molecular relationships of clinical
      strains of Streptococcus agalactiae.
AB  - Mechanisms for tetracycline and macrolide resistance in 54 isolates of
      erythromycin-resistant Streptococcus agalactiae were analyzed by PCR. The erm(B),
      erm(A), and mef(A) genes, either alone or in combination, were detected in all
      the erythromycin-resistant isolates. The tet(M) and tet(O) genes were responsible
      for tetracycline resistance. Random amplification of polymorphic DNA indicated
      different clonal origins of the isolates.

PMID- 11959605
TI  - In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B,
      and fluconazole against 37 clinical isolates of zygomycetes.
AB  - In vitro antifungal susceptibility testing results of a new antifungal triazole,
      posaconazole (POS), were compared to results with amphotericin B (AMB),
      itraconazole (ITC), voriconazole (VRC), and fluconazole (FLC) against clinical
      agents of zygomycosis. The MICs of POS at which 50% and 90% of the isolates were
      inhibited were 0.25 and 4 microg/ml, respectively. POS was significantly more
      active than VRC and FLC and slightly more active than ITC. The results suggest
      that POS has significant potential for clinical development against the
      zygomycetes.

PMID- 11959604
TI  - Outbreak of infections caused by Enterobacter cloacae producing the integron
      associated beta-lactamase IBC-1 in a neonatal intensive care unit of a Greek
      hospital.
AB  - Nineteen of 27 ceftazidime-resistant Enterobacter cloacae isolates from a
      neonatal intensive care unit in Thessaloniki, Greece, had genes coding for the
      novel extended-spectrum beta-lactamase IBC-1; 18 of those 19 harbored similar
      conjugative plasmids and belonged to two distinct genetic lineages. A synergy
      test with ceftazidime and imipenem enabled us to identify five unrelated bla(IBC
      1)-carrying E. cloacae isolates from other wards of the hospital. It seems that
      this integron-associated gene is capable of dispersing both by clonal spread and
      by gene dissemination.

PMID- 11959606
TI  - In vitro activities of free and lipid formulations of amphotericin B and nystatin
      against clinical isolates of Coccidioides immitis at various saprobic stages.
AB  - We investigated the susceptibilities of hyphal, mixed hyphal, ungerminated
      arthroconidial, and germinated arthroconidial populations of Coccidioides immitis
      to lipid formulations of amphotericin B and nystatin and their conventional
      preparations, utilizing the National Committee for Clinical Laboratory Standards
      M38-P broth macrodilution method. The differences in effects of the three
      different growth stages of the saprobic phase of C. immitis on the MIC/minimum
      lethal concentration (MLC) ratio were not statistically significant for any of
      the antifungal agents tested. These results suggest that either inocula could be
      used for in vitro susceptibility studies with C. immitis.

PMID- 11959607
TI  - Human immunodeficiency virus (HIV) Type 1 reverse transcriptase resistance
      mutations in hepatitis B virus (HBV)-HIV-coinfected patients treated for HBV
      chronic infection once daily with 10 milligrams of adefovir dipivoxil combined
      with lamivudine.
AB  - Adefovir dipivoxil (ADV) at a suboptimal concentration for human immunodeficiency
      virus type 1 (HIV-1) (10 mg once daily) can be used to treat hepatitis B virus
      (HBV) infection in HIV-1-HBV-coinfected patients and does not, even in the case
      of uncontrolled HIV-1 replication, select for either ADV mutations at codons 65
      and 70 or any other particular HIV-1 reverse transcriptase resistance profile.

PMID- 11959608
TI  - Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice.
AB  - In this crossover study in 12 healthy volunteers, coadministration of amprenavir
      (1,200 mg; single dose) with grapefruit juice slightly reduced the maximum
      concentration of drug in serum (Cmax) compared to administration with water (7.11
      versus 9.10 microg/ml), slightly increased the time to Cmax (1.13 versus 0.75 h),
      and did not affect the area under the concentration-time curve from 0 to 12 h
      (AUC(0-12)), the AUC(0-infinity), or the concentration at 12 h. Therefore,
      grapefruit juice does not clinically significantly affect amprenavir
      pharmacokinetics.

PMID- 11959609
TI  - Different aminoglycoside-resistant phenotypes in a rabbit Staphylococcus aureus
      endocarditis infection model.
AB  - The impact of different types of enzymatic resistance on the in vivo
      antibacterial activity of aminoglycosides (amikacin, gentamicin, and netilmicin)
      was studied in the rabbit endocarditis model with four strains of Staphylococcus
      aureus. Animals were treated in a manner simulating the administration of a
      single daily human dose. Amikacin had no effect on the three kanamycin-resistant
      strains despite apparent susceptibility in the disk diffusion test. Gentamicin
      appears to be the preferable aminoglycoside for treatment of staphylococcal
      infections.

PMID- 11959610
TI  - Distribution of azithromycin in plasma and tonsil tissue after repeated oral
      administration of 10 or 20 milligrams per kilogram in pediatric patients.
AB  - Azithromycin concentrations in the tonsils of 56 pediatric patients, treated with
      10 or 20 mg of the drug per kg of body weight for 3 days, were compared.
      Azithromycin levels in plasma and tonsil samples were determined up to 8.5 days
      after the last dose. The 20-mg/kg regimen resulted in an improved tonsillar
      distribution of azithromycin, suggesting the achievement of enhanced therapeutic
      concentrations at infective sites of the upper respiratory tract.

PMID- 11959611
TI  - Design and antileishmanial activity of amphotericin B-loaded stable ionic
      amphiphile biovector formulations.
AB  - A new delivery system, Ionic Amphiphilic Biovector (ABV), comprised of anionic
      lipids (dipalmitoyl phosphatidyl glycerol) included in a cationic cross-linked
      polysaccharide matrix was used as a reservoir for amphotericin B (AmB). Two ABV
      formulations exhibited an in vitro and in vivo efficacy similar to commercial
      AmBisome against Leishmania donovani-infected mice. The higher stability of these
      ABV formulations indicates their potential for further development and
      applications.

PMID- 11959612
TI  - Site-specific recombination with the chromosomal tRNA(Leu) gene by the large
      conjugative Haemophilus resistance plasmid.
AB  - Characterization of the sequences involved in recombination of the Haemophilus
      plasmid p1056 with the Haemophilus influenzae chromosome produced evidence
      indicating site-specific recombination with chromosomal tRNA(Leu). attP sequences
      identical to those of p1056 were found in six plasmids of diverse origin,
      suggesting that a family of Haemophilus plasmids recombines with chromosomal
      tRNA(Leu).

PMID- 11959613
TI  - Characterization of a laboratory-derived, high-level ampicillin-resistant
      Salmonella enterica serovar Typhimurium strain that caused meningitis in an
      infant.
AB  - A Salmonella enterica serovar Typhimurium strain that harbored a plasmid carrying
      a TEM-1-type beta-lactamase gene was isolated from the blood and cerebrospinal
      fluid of an infant with meningitis. This 3.2-kb plasmid was further characterized
      to be a nonconjugative pGEM series cloning vector containing a foreign insert.
      The strain was likely laboratory derived and contaminated the environment before
      it caused the infection.

PMID- 11959614
TI  - Gemifloxacin is efficacious against penicillin-resistant and quinolone-resistant
      pneumococci in experimental meningitis.
AB  - In experimental rabbit meningitis, gemifloxacin penetrated inflamed meninges well
      (22 to 33%) and produced excellent bactericidal activity (change in log(10)
      [Deltalog(10)] CFU/ml/h, -0.68 +/- 0.30 [mean and standard deviation]), even
      superior to that of the standard regimen of ceftriaxone plus vancomycin (-0.49 +/
      0.09 deltalog(10) CFU/ml/h), in the treatment of meningitis due to a penicillin
      resistant pneumococcal strain (MIC, 4 mg/liter). Even against a penicillin- and
      quinolone-resistant strain, gemifloxacin showed good bactericidal activity (-0.48
      +/- 0.16 deltalog(10) CFU/ml/h). The excellent antibacterial activity of
      gemifloxacin was also confirmed by time-kill assays over 8 h in vitro.

PMID- 11959615
TI  - Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA
      polymerases alpha, delta, and epsilon*.
AB  - Tenofovir diphosphate (PMPApp) is a weak inhibitor of DNA polymerases (pol)
      alpha, delta, and epsilon*, with values for the Ki for PMPApp ((PMPApp)Ki)
      relative to the Km for dATP ((dATP)Km) of 10.2, 10.2, and 15.2, respectively. Its
      incorporation into DNA was about 1,000-fold less efficient than that of dATP,
      with (PMPApp)Km values 350-, 2,155-, and 187-fold higher than (dATP)Km values for
      pol alpha, delta, and epsilon*, respectively.

PMID- 11959616
TI  - Interaction between grapefruit juice and praziquantel in humans.
AB  - After a single oral dose of praziquantel with 250 ml of grapefruit juice, the
      area under the concentration-time curve and the maximum concentration in plasma
      of praziquantel (Cmax) were significantly increased (Cmax for water treatment,
      637.71 +/- 128.5 ng/ml; and Cmax for grapefruit juice treatment, 1,037.65 +/-
      305.7 ng/ml, P < 0.05). No statistically significant differences were found in
      the time to maximum concentration of drug in plasma or elimination half-life.

PMID- 11959617
TI  - In vitro activity of linezolid against Clostridium difficile.
AB  - We examined the in vitro activity of linezolid against Clostridium difficile,
      including isolates with reduced susceptibility to metronidazole or vancomycin.
      The MIC at which 50% of the isolates were inhibited (MIC50) and MIC90 were 0.5
      and 2 microg/ml, respectively (range, 0.03 to 4 microg/ml). MICs were always <or=
      4 microg/ml, and thus, all isolates were considered susceptible.

PMID- 11959618
TI  - Ca(2+) oscillations, gradients, and homeostasis in vascular smooth muscle.
AB  - Vascular smooth muscle shows both plasticity and heterogeneity with respect to
      Ca(2+) signaling. Physiological perturbations in cytoplasmic Ca(2+) concentration
      ([Ca(2+)](i)) may take the form of a uniform maintained rise, a transient uniform
      [Ca(2+)](i) elevation, a transient localized rise in [Ca(2+)](i) (also known as
      spark and puff), a transient propagated wave of localized [Ca(2+)](i) elevation
      (Ca(2+) wave), recurring asynchronous Ca(2+) waves, or recurring synchronized
      Ca(2+) waves dependent on the type of blood vessel and the nature of stimulation.
      In this overview, evidence is presented which demonstrates that interactions of
      ion transporters located in the membranes of the cell, sarcoplasmic reticulum,
      and mitochondria form the basis of this plasticity of Ca(2+) signaling. We focus
      in particular on how the junctional complexes of plasmalemma and superficial
      sarcoplasmic reticulum, through the generation of local cytoplasmic Ca(2+)
      gradients, maintain [Ca(2+)](i) oscillations, couple these to either contraction
      or relaxation, and promote Ca(2+) cycling during homeostasis.

PMID- 11959619
TI  - Effect of endovascular cooling on myocardial temperature, infarct size, and
      cardiac output in human-sized pigs.
AB  - Mild hypothermia reduces myocardial infarct size in small animals; however, the
      extent of myocardial protection in large animals with greater thermal mass
      remains unknown. We evaluated the effects of mild endovascular cooling on
      myocardial temperature, infarct size, and cardiac output in 60- to 80-kg
      isoflurane-anesthetized pigs. We occluded the left anterior descending coronary
      artery for 60 min, followed by reperfusion for 3 h. An endovascular heat-exchange
      catheter was used to either lower core body temperature to 34 degrees C (n = 11)
      or maintain temperature at 38 degrees C (n = 11). Additional studies assessed
      myocardial viability and microvascular perfusion with (99m)Tc-sestamibi
      autoradiography. Endovascular cooling reduced infarct size compared with
      normothermia (9 +/- 6% vs. 45 +/- 8% of the area at risk; P < 0.001), whereas the
      area at risk was comparable (19 +/- 3% vs. 20 +/- 7%; P = 0.65). Salvaged
      myocardium showed normal sestamibi uptake, confirming intact microvascular flow
      and myocyte viability. Cardiac output was maintained in hypothermic hearts
      because of an increase in stroke volume, despite a decrease in heart rate. Mild
      endovascular cooling to 34 degrees C lowers myocardial temperature sufficiently
      in human-sized hearts to cause a substantial cardioprotective effect, preserve
      microvascular flow, and maintain cardiac output.

PMID- 11959620
TI  - Central mechanisms of acute ANG II modulation of arterial baroreflex control of
      renal sympathetic nerve activity.
AB  - Short-term intravenous infusion of angiotensin II (ANG II) into conscious rabbits
      reduces the range of renal sympathetic nerve activity (RSNA) by attenuating
      reflex disinhibition of RSNA. This action of ANG II to attenuate the arterial
      baroreflex range is exaggerated when ANG II is directed into the vertebral
      circulation, which suggests a mechanism involving the central nervous system.
      Because an intact area postrema (AP) is required for ANG II to attenuate arterial
      baroreflex-mediated bradycardia and is also required for maintenance of ANG II
      dependent hypertension, we hypothesized that attenuation of maximum RSNA during
      infusion of ANG II involves the AP. In conscious AP-lesioned (APX) and AP-intact
      rabbits, we compared the effect of a 5-min intravenous infusion of ANG II (10 and
      20 ng x kg(-1) x min(-1)) on the relationship between mean arterial blood
      pressure (MAP) and RSNA. Intravenous infusion of ANG II into AP-intact rabbits
      resulted in a dose-related attenuation of maximum RSNA observed at low MAP. In
      contrast, ANG II had no effect on maximum RSNA in APX rabbits. To further
      localize the central site of ANG II action, its effect on the arterial baroreflex
      was assessed after a midcollicular decerebration. Decerebration did not alter
      arterial baroreflex control of RSNA compared with the control state, but as in
      APX, ANG II did not attenuate the maximum RSNA observed at low MAP. The results
      of this study indicate that central actions of peripheral ANG II to attenuate
      reflex disinhibition of RSNA not only involve the AP, but may also involve a
      neural interaction rostral to the level of decerebration.

PMID- 11959621
TI  - Effect of repeated episodes of reversible myocardial ischemia on myocardial blood
      flow and function in humans.
AB  - Nine patients with coronary artery disease and normal left ventricular (LV)
      function underwent two episodes of dobutamine-induced ischemia to determine
      whether repeated episodes of ischemia lead to cumulative stunning. Positron
      emission tomography (PET) and oxygen 15-labeled H(2)O was used to assess
      myocardial blood flow (MBF) at baseline, peak stress, and after stress for each
      ischemic episode. Quantitative echocardiographic assessment of global ejection
      fraction (EF) and regional systolic function (SF) was performed at rest and
      regular intervals after dobutamine. SF was assessed for regions subtended by a
      coronary artery with a >70% diameter stenosis. Both EF and SF were more severely
      impaired 45 min after the second episode of stress compared with 45 min after the
      first (both P < 0.01), despite no difference in duration of the two dobutamine
      infusions or MBF at peak stress (1.72 vs. 1.69). After both episodes of ischemia,
      when LV function was impaired but subsequently recovered, MBF (1.15 +/- 0.39 and
      1.20 +/- 0.43, respectively) was no different to baseline MBF (1.02 +/- 0.35),
      confirming that repeated episodes of dobutamine-induced ischemia lead to
      cumulative myocardial stunning.

PMID- 11959622
TI  - A novel approach to blood plasma viscosity measurement using fluorescent
      molecular rotors.
AB  - Molecular rotors, a group of fluorescent molecules with viscosity-dependent
      quantum yield, were tested for their suitability to act as fluorescence-based
      plasma viscometers. The viscosity of samples of human plasma was modified by the
      addition of pentastarch (molecular mass 260 kDa, 10% solution in saline) and
      measured with a Brookfield viscometer. Plasma viscosity was 1.6 mPa x s, and the
      mixtures ranged up to 4.5 mPa x s (21 degrees C). The stimulated light emission
      of the molecular rotors mixed in the plasma samples yielded light intensity that
      was nonoverlapping and of significantly different intensity for viscosity steps
      down to 0.3 mPa x s (n = 5, P < 0.0001). The mathematical relationship between
      intensity (I) and viscosity (eta) was found to be eta = (kappaI)(nu). After
      calibration and scaling the fluorescence based measurement had an average
      deviation versus the conventional viscometric measurements that was <1.8%. These
      results show the suitability of molecular rotors for fast, low-volume biofluid
      viscosity measurements achieving accuracy and precision comparable to mechanical
      viscometers.

PMID- 11959623
TI  - GABA(A) receptor activation at medullary sympathetic neurons contributes to
      postexercise hypotension.
AB  - A single bout of exercise results in a postexercise hypotension (PEH) that is
      accompanied by a reduced baroreflex function. Based on the role of rostral
      ventrolateral medulla (RVLM) neurons in controlling sympathetic nerve activity
      (SNA) and blood pressure, the role of gamma-aminobutyric acid (GABA) in
      controlling RVLM neuronal activity, and the reduced baroreflex-SNA relationship
      during PEH, we determined whether: 1) RVLM neuronal activity is decreased during
      PEH, 2) GABA(A)-receptor mechanisms mediate the decrease, and 3) baroreflex
      control of RVLM activity is reduced. Spontaneously hypertensive rats (SHR) were
      subjected to 40 min of treadmill or sham exercise (Sham PEH). PEH lasted 10 h in
      conscious and anesthetized SHR, indicating that the anesthetics did not affect
      the expression of PEH. Extracellular RVLM neuronal activity having a cardiac and
      sympathetic rhythm, lumbar SNA, and blood pressure were recorded at rest and
      during baroreflex function curves. Resting RVLM neuronal activity was lower and
      was increased to a greater extent by GABA(A)-receptor antagonism in PEH versus
      Sham PEH (P < 0.05). Baroreflex control of RVLM neuronal activity operated with a
      reduced gain (P < 0.05). Thus increased GABA signaling at RVLM neurons may
      contribute to PEH.

PMID- 11959624
TI  - Protein kinase C-delta modulates apoptosis induced by hyperglycemia in adult
      ventricular myocytes.
AB  - We evaluated the direct effect of hyperglycemia on apoptosis of adult rat
      ventricular myocytes (ARVM) in vitro. Hyperglycemia (16.5 mM) for 24 h increased
      apoptosis by greater than threefold (48.2 +/- 4.4%, by the TdT-mediated dUTP nick
      end labeling method) compared with baseline (14.7 +/- 2.5%). Hyperosmolarity with
      mannitol (11.0 mM) in the presence of 5.5 mM glucose also increased apoptosis by
      approximately twofold of baseline. Both glucose and mannitol treatment resulted
      in the membrane translocation of protein kinase C (PKC)-delta, and the activation
      of PKC-delta was confirmed by immune complex kinase assay. PKC-delta-specific
      translocation inhibitor peptide (deltaV1-1) attenuated only apoptosis induced by
      hyperglycemia but not by mannitol. A PKC-epsilon-specific translocation inhibitor
      peptide (epsilonV1-1) affected neither type of apoptosis. Moderate overexpression
      of PKC-delta by adenovirus gene transfer prevented the antiapoptotic effect of
      deltaV1-1. Furthermore, deltaV1-1 attenuated the production of reactive oxygen
      species (ROS) by glucose. Taken together, our results indicate that increased ROS
      production regulated by PKC-delta is in part responsible for the induction of
      apoptosis by hyperglycemia and that apoptosis by hyperglycemia is mechanistically
      different from that by hyperosmolarity.

PMID- 11959625
TI  - Effect of AT(1) receptor blockade on cardiac apoptosis in angiotensin II-induced
      hypertension.
AB  - Angiotensin II (ANG II) via AT(1) receptors induces apoptosis in cardiomyocytes
      in vitro. We tested the hypothesis that in vivo AT(1) receptor stimulation is
      accompanied by cardiac apoptosis and attempted to elucidate the molecular
      mechanisms involved in the death signaling pathway. Male Sprague-Dawley rats
      received ANG II (120 ng x kg(-1) x min(-1) sc) for 7 days with or without the
      AT(1) receptor antagonist losartan (10 mg x kg(-1) x day(-1) orally). Cardiac
      function was assessed by echocardiography. Apoptosis in the heart was detected
      and quantified by in situ TdT-mediated dUTP nick-end labeling (TUNEL) and
      radiolabeled DNA laddering. Expression of bax, bcl-2, caspase 3, and AT(1) and
      AT(2) receptors was examined by Western blot analysis. Activity of caspase 3 was
      also measured by a fluorometric immunosorbent enzyme assay. Tail cuff systolic
      blood pressure was elevated (P < 0.01, n = 6) in ANG II-infused rats (173 +/- 3
      mmHg) versus controls (111 +/- 2 mmHg) and reduced by losartan (134 +/- 4 mmHg).
      Cardiac function was essentially unchanged in ANG II-infused rats. Increased
      internucleosomal DNA cleavage by TUNEL assay and radiolabeled DNA laddering
      showed results compatible with enhanced cardiomyocyte apoptosis in the hearts of
      ANG-II infused rats. The bax-to-bcl-2 ratio, expression of the active form of
      caspase 3 (17 kDa), and activity of caspase 3 in the hearts of the ANG II group
      increased more than twofold above controls. Protein expression of AT(1) and AT(2)
      receptors was significantly increased in ANG II-infused rats compared with
      control rats. Losartan-treated ANG II-infused rats exhibited normalized
      apoptosis, bax, caspase 3 activity, and AT(1) receptors. ANG II stimulation of
      AT(1) receptors in the heart in vivo is associated with an increased rate of
      apoptosis without major hemodynamic consequences. Bax and caspase 3 are involved
      in the apoptotic signaling pathway in this experimental paradigm.

PMID- 11959626
TI  - Cardiac contractility modulation by electric currents applied during the
      refractory period.
AB  - Inotropic effects of electric currents applied during the refractory period have
      been reported in cardiac muscle in vitro using voltage-clamp techniques. We
      investigated how electric currents modulate cardiac contractility in normal
      canine hearts in vivo. Six dogs were instrumented to measure regional segment
      length, ventricular volume (sonomicrometry), and ventricular pressure. Cardiac
      contractility modulating (CCM) electric currents (biphasic square pulses,
      amplitude +/-20 mA, total duration 30 ms) were delivered during the refractory
      period between pairs of electrodes placed on anterior and posterior walls. CCM
      significantly increased index of global contractility (E(es)) from 5.9 +/- 2.9 to
      8.3 +/- 4.6 mmHg/ml with anterior CCM, from 5.3 +/- 1.8 to 8.9 +/- 4.0 mmHg/ml
      with posterior CCM, and from 6.1 +/- 2.6 to 11.0 +/- 7.0 mmHg/ml with combined
      CCM (P < 0.01, no significant change in volume axis intercept). End-systolic
      pressure-segment length relations showed contractility enhancement near CCM
      delivery sites, but not remotely. Relaxation was not influenced. CCM increased
      mean aortic pressure, but did not change peripheral resistance. Locally applied
      electrical currents enhanced global cardiac contractility via regional changes in
      myocardial contractility without impairing relaxation in situ.

PMID- 11959627
TI  - Vascular smooth muscle cell membrane depolarization after NOS inhibition
      hypertension.
AB  - Nitric oxide (NO) synthase (NOS) inhibition with N(omega)-nitro-L-arginine (L
      NNA) produces L-NNA hypertensive rats (LHR), which exhibit increased sensitivity
      to voltage-dependent Ca(2+) channel-mediated vasoconstriction. We hypothesized
      that enhanced contractile responsiveness after NOS inhibition is mediated by
      depolarization of membrane potential (E(m)) through attenuated K(+) channel
      conductance. E(m) measurements demonstrated that LHR vascular smooth muscle cells
      (VSMCs) are depolarized in open, nonpressurized (-44.5 +/- 1.0 mV in control vs. 
      36.8 +/- 0.8 mV in LHR) and pressurized mesenteric artery segments (-41.8 +/- 1.0
      mV in control vs. -32.6 +/- 1.4 mV in LHR). Endothelium removal or exogenous L
      NNA depolarized control VSMCs but not LHR VSMCs. Superfused L-arginine
      hyperpolarized VSMCs from both the control and LHR groups and reversed L-NNA
      induced depolarization (-44.5 +/- 1.0 vs. -45.8 +/- 2.1 mV). A Ca(2+)-activated
      K(+) channel agonist, NS-1619 (10 microM), hyperpolarized both groups of arteries
      to a similar extent (from -50.8 +/- 1.0 to -62.5 +/- 1.2 mV in control and from 
      43.7 +/- 1.1 to -55.6 +/- 1.2 mV in LHR), although E(m) was still different in
      the presence of NS-1619. In addition, superfused iberiotoxin (50 nM) depolarized
      both groups similarly. Increasing the extracellular K(+) concentration from 1.2
      to 45 mM depolarized E(m), as predicted by the Goldman-Hodgkin-Katz equation.
      These data support the hypothesis that loss of NO activation of K(+) channels
      contributes to VSMC depolarization in L-NNA-induced hypertension without a change
      in the number of functional large conductance Ca(2+)-activated K(+) channels.

PMID- 11959628
TI  - 14,15-Dihydroxyeicosatrienoic acid relaxes bovine coronary arteries by activation
      of K(Ca) channels.
AB  - Epoxyeicosatrienoic acids (EETs) cause vascular relaxation by activating smooth
      muscle large conductance Ca(2+)-activated K(+) (K(Ca)) channels. EETs are
      metabolized to dihydroxyeicosatrienoic acids (DHETs) by epoxide hydrolase. We
      examined the contribution of 14,15-DHET to 14,15-EET-induced relaxations and
      characterized its mechanism of action. 14,15-DHET relaxed U-46619-precontracted
      bovine coronary artery rings but was approximately fivefold less potent than
      14,15-EET. The relaxations were inhibited by charybdotoxin, iberiotoxin, and
      increasing extracellular K(+) to 20 mM. In isolated smooth muscle cells, 14,15
      DHET increased an iberiotoxin-sensitive, outward K(+) current and increased K(Ca)
      channel activity in cell-attached patches and inside-out patches only when GTP
      was present. 14,15-[(14)C]EET methyl ester (Me) was converted to 14,15
      [(14)C]DHET-Me, 14,15-[(14)C]DHET, and 14,15-[(14)C]EET by coronary arterial
      rings and endothelial cells but not by smooth muscle cells. The metabolism to
      14,15-DHET was inhibited by the epoxide hydrolase inhibitors 4-phenylchalcone
      oxide (4-PCO) and BIRD-0826. Neither inhibitor altered relaxations to
      acetylcholine, whereas relaxations to 14,15-EET-Me were increased slightly by
      BIRD-0826 but not by 4-PCO. 14,15-DHET relaxes coronary arteries through
      activation of K(Ca) channels. Endothelial cells, but not smooth muscle cells,
      convert EETs to DHETs, and this conversion results in a loss of vasodilator
      activity.

PMID- 11959629
TI  - Cardiac troponin T isoforms demonstrate similar effects on mechanical performance
      in a regulated contractile system.
AB  - Alteration of troponin T (TnT) isoform expression has been reported in human and
      animal models of myocardial failure. The two adult beef cardiac TnT isoforms
      (TnT(3) and TnT(4)) were isolated for comparative functional analysis. Thin
      filaments were reconstituted containing pure populations of the isoforms. The in
      vitro motility assay was used to directly compare the effect of the two TnT
      isoforms on force and unloaded shortening as a function of free calcium. We found
      no significant differences between the two isoforms in terms of calcium
      sensitivity, cooperativity, or maximal activation (velocity and force) as
      assessed in a fully calcium-regulated system. Activation by myosin strong binding
      was similar for thin filaments containing either of the two TnT isoforms. Whereas
      maximally activated velocity and cooperativity was depressed at pH 6.5, no
      difference between thin filaments containing the two isoforms was detected. From
      the small magnitude of the TnT isoform shifts detected in myocardial failure and
      the lack of significant mechanical effect detected in the motility assay,
      variable TnT isoform expression is unlikely to be any functional significance in
      heart failure.

PMID- 11959630
TI  - Targeted myocardial transgenic expression of HIV Tat causes cardiomyopathy and
      mitochondrial damage.
AB  - Cardiac effects of human immunodeficiency virus (HIV) transactivator (Tat) are
      unclear, but Tat decreases liver glutathione (an important mitochondrial
      antioxidant) when ubiquitously expressed in transgenic mice (TG). With an alpha
      myosin heavy chain promoter, Tat was selectively targeted to murine cardiac
      myocytes. One high-expression hemizygous ((+/-)Tat(high); 12 copies) and two low
      expression ((+/-)Tat(lowA,B); 2-5 copies) TG lines were created. Cardiomyopathy
      was documented with increased left ventricle (LV) mass, ventricular expression of
      atrial natriuretic factor (ANF) mRNA, mitochondrial ultrastructural defects, and
      myocardial depletion of glutathione. In (+/-)Tat(high) TGs, normalized LV mass
      (determined echocardiographically) increased 46% (90 days), 134% (240 days), and
      96% (365 days) compared with wild-type littermates (WT). LV fractional shortening
      was decreased to 28% (90 days), 27% (240 days), and 19% (365 days). (+/-)Tat(low)
      LV mass was unchanged (<or=365 days). ANF in (+/-)Tat(high) ventricles (180 days)
      was twofold WT values. Glutathione was selectively decreased in (+/-)Tat(high)
      hearts (120 days). (+/-)Tat(high) hearts contained damaged mitochondria (>or=210
      days); however, profound mitochondrial destruction occurred in homozygous
      (+/+)Tat(high) hearts (10 days) and the pups died (14 days). Tat caused cardiac
      dysfunction in this TG and may impact on cardiomyopathy in acquired
      immunodeficiency syndrome.

PMID- 11959631
TI  - Inhibition of neurons in commissural nucleus of solitary tract reduces
      sympathetic nerve activity in SHR.
AB  - Neurons in the commissural nucleus of the solitary tract (commNTS) play an
      important role in certain cardiovascular responses dependent on sympathetic
      vasoconstrictor activation, including the arterial chemoreceptor reflex.
      Electrolytic lesions of the commNTS elicit a fall in arterial pressure (AP) in
      spontaneously hypertensive rats (SHR). To determine whether the latter result 1)
      arose from elimination of commNTS neuronal activity rather than en passant axons
      and 2) was accompanied by a reduction in sympathetic nerve activity, we evaluated
      the effect of inhibition of neurons in the commNTS on basal splanchnic
      sympathetic nerve activity (SNA), AP, and heart rate (HR) in SHR, Wistar-Kyoto
      (WKY), and Sprague-Dawley (SD) rats. In chloralose-anesthetized, paralyzed, and
      artificially ventilated SHR, microinjection of GABA into the commNTS markedly
      decreased splanchnic SNA, AP, and HR. The reductions in SNA and AP following
      similar microinjections in WKY and SD rats were significantly less than those in
      SHR. Our findings suggest that tonically active neurons in the commNTS contribute
      to the maintenance of SNA and the hypertension in SHR. The level of tonic
      discharge of these commNTS neurons in normotensive WKY and SD rats may be lower
      than in SHR.

PMID- 11959632
TI  - Decreased Smad 7 expression contributes to cardiac fibrosis in the infarcted rat
      heart.
AB  - We examined the role of the transforming growth factor (TGF)-beta(1) signaling
      inhibitor Smad 7 in cardiac fibrosis. TGF-beta(1) (10 ng/ml) was found to
      increase cytosolic Smad 7 expression in primary adult rat fibroblasts and induce
      rapid nuclear export of exogenous Smad 7 in COS-7 cells. Furthermore,
      overexpression of Smad 7 in primary adult fibroblasts was associated with
      suppressed collagen type I and III expression. We detected Smad 7, phosphorylated
      Smad 2, TGF-beta type I receptor (TbetaRI), and TGF-beta(1) proteins in
      postmyocardial infarct (MI) rat hearts. In 2 and 4 wk post-MI hearts, Smad 7 and
      TbetaRI expression were decreased in scar tissue, whereas TGF-beta(1) expression
      was increased in scar and viable tissue. In the 8 wk post-MI heart, Smad 7
      expression was decreased in both scar tissue and myocardium remote to the infarct
      scar. Finally, we confirmed that these changes are paralleled by decreased
      expression of cytosolic phosphorylated receptor-regulated Smad 2 in 4-wk viable
      myocardium and in 2- and 4-wk infarct scar tissues. Taken together, our data
      imply that decreased inhibitory Smad 7 signal in cardiac fibroblasts may play a
      role in the pathogenesis of cardiac fibrosis in the post-MI heart.

PMID- 11959633
TI  - Role of superoxide anion in regulating pressor and vascular hypertrophic response
      to angiotensin II.
AB  - Our purpose was to address the role of NAPDH oxidase-derived superoxide anion in
      the vascular response to ANG II. Blood pressure, aortic superoxide anion, 3
      nitrotyrosine, and medial cross-sectional area were compared in wild-type mice
      and in mice that overexpress human superoxide dismutase (hSOD). The pressor
      response to ANG II was significantly less in hSOD mice. Superoxide anion levels
      were increased twofold in ANG II-treated wild-type mice but not in hSOD mice. 3
      Nitrotyrosine increased in aortic endothelium and adventitia in wild-type but not
      hSOD mice. In contrast, aortic medial cross-sectional area increased 50% with ANG
      II in hSOD mice, comparable to wild-type mice. The lower pressor response to ANG
      II in the mice expressing hSOD is consistent with a pressor role of superoxide
      anion in wild-type mice, most likely because it reacts with nitric oxide. Despite
      preventing the increase in superoxide anion and 3-nitrotyrosine, the aortic
      hypertrophic response to ANG II in vivo was unaffected by hSOD.

PMID- 11959634
TI  - Echocardiographic assessment of LV hypertrophy and function in aortic-banded
      mice: necropsy validation.
AB  - We characterized the time course of the left ventricular (LV) geometric and
      functional changes after aortic banding, validated them by necropsy, and
      investigated the sensitivity of echocardiographic findings on LV hypertrophy.
      C57BL/6 mice were subjected to transverse aortic constriction (TAC) or sham
      operation; echocardiographic assessments were performed before or at 2, 4, 6, and
      11 wk after surgery; and some of the mice were euthanized at the corresponding
      time points. There was a progressive increase in diastolic posterior wall
      thickness and LV systolic dimension; the percentage of LV fractional shortening
      (LV%FS) decreased progressively at 4 wk, whereas these parameters remained stable
      in sham-operated mice. Echo LV mass and LV%FS correlated well with actual whole
      heart mass and ratio of lung weight to body weight, respectively (r = 0.765 and 
      0.749, respectively; P < 0.0001). These results suggest that the development of
      myocardial hypertrophy and systolic dysfunction is a time-dependent process.
      Echocardiographic assessment of myocardial hypertrophy and functional changes
      correlate well with the actual heart mass and lung mass. Echocardiography is
      sensitive enough to assess myocardial hypertrophy and heart functional changes
      induced by pressure overload in mice.

PMID- 11959635
TI  - Induction of apoptosis in vascular smooth muscle cells by mechanical stretch.
AB  - We studied the response of porcine vascular smooth muscle cells (PVSMCs) to
      cyclic sinusoidal stretch at a frequency of 1 Hz. Cyclic stretch with an area
      change of 25% caused an increase in PVSMC apoptosis, which was accompanied by
      sustained activation of c-Jun NH(2)-terminal kinases (JNK) and the mitogen
      activated protein kinase p38. Cyclic stretch with an area change of 7% had no
      such effect. Infection of PVSMCs with recombinant adenoviruses expressing
      constitutively active forms of upstream molecules that activate JNK and p38 also
      led to apoptosis. The simultaneous blockade of both JNK and p38 pathways with
      adenovirus-mediated expression of dominant-negative mutants of c-Jun and p38
      caused a significant decrease (to 1/2) of the apoptosis induced by 25% cyclic
      stretch. The 25% stretch also caused sustained clustering of tumor necrosis
      factor-alpha (TNF-alpha) receptor-1 and its association with TNF-alpha receptor
      associated factor-2 (TRAF-2). Overexpressing the wild-type TRAF-2 in PVSMCs
      caused an increase in apoptosis. In contrast, the expression of a dominant
      negative mutant of TRAF-2 attenuated stretch-induced apoptois. These results
      support the hypothesis that circumferential overload under hypertensive
      conditions induces a clustering of death receptors that cause vascular smooth
      muscle cell apoptosis.

PMID- 11959636
TI  - Baroreflex modulation of muscle sympathetic nerve activity during cold pressor
      test in humans.
AB  - The purpose of this project was to test the hypothesis that baroreceptor
      modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered
      during the cold pressor test. Ten subjects were exposed to a cold pressor test by
      immersing a hand in ice water for 3 min while arterial blood pressure, heart
      rate, and MSNA were recorded. During the second and third minute of the cold
      pressor test, blood pressure was lowered and then raised by intravenous bolus
      infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope
      of the relationship between MSNA and diastolic blood pressure was more negative
      (P < 0.005) during the cold pressor test (-244.9 +/- 26.3 units x beat(-1) x
      mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1)
      x mmHg(-1)), whereas no significant change in the slope of the relationship
      between heart rate and systolic blood pressure was observed. These data suggest
      that baroreceptors remain capable of modulating MSNA and heart rate during a cold
      pressor test; however, the sensitivity of baroreflex modulation of MSNA is
      elevated without altering the sensitivity of baroreflex control of heart rate.

PMID- 11959637
TI  - Mechanism of cGMP contribution to the vasodilator response to NO in rat middle
      cerebral arteries.
AB  - This study examined the mechanism by which cGMP contributes to the vasodilator
      response to nitric oxide (NO) in rat middle cerebral arteries (MCA).
      Administration of a NO donor, diethylaminodiazen-1-ium-1,2-dioate (DEA-NONOate),
      or 8-bromo-cGMP (8-BrcGMP) increased the diameter of serotonin-preconstricted MCA
      by 79 +/- 3%. The response to DEA-NONOate, but not 8-BrcGMP, was attenuated by
      iberiotoxin (10(-7) M) or a 80 mM high-K(+) media, suggesting that activation of
      K(+) channels contributes to the vasodilator response to NO but not 8-BrcGMP. The
      effects of NO and cGMP on the vasoconstrictor response to Ca(2+) were also
      studied in MCA that were permeabilized with alpha-toxin and ionomycin. Elevations
      in bath Ca(2+) from 10(-8) to 10(-5) M decreased the diameter of permeabilized
      MCA by 76 +/- 5%. DEA-NONOate (10(-6) M) and 8-BrcGMP (10(-4) M) blunted this
      response by 60%. Inhibition of guanylyl cyclase with 1H-[1,2,4]oxadiazole[4,3-a]
      quinoxalin-1-one (10(-5) M) blocked the inhibitory effect of the NO donor, but
      not 8-BrcGMP, on Ca(2+)-induced vasoconstriction. 8-BrcGMP (10(-4) M) had no
      effect on intracellular Ca(2+) concentration ([Ca(2+)](i)) in control, serotonin
      stimulated, or alpha-toxin- and ionomycin-permeabilized vascular smooth muscle
      cells isolated from the MCA. These results indicate that the vasodilator response
      to NO in rat MCA is mediated by activation of Ca(2+)-activated K(+) channels via
      a cGMP-independent pathway and that cGMP also contributes to the vasodilator
      response to NO by decreasing the contractile response to elevations in
      [Ca(2+)](i).

PMID- 11959638
TI  - Threshold effects of respiratory muscle work on limb vascular resistance.
AB  - The purpose of this study was to determine whether the human diaphragm, like limb
      muscle, has a threshold of force output at which a metaboreflex is activated
      causing systemic vasoconstriction. We used Doppler ultrasound techniques to
      quantify leg blood flow (Q(L)) and utilized the changes in mouth twitch pressure
      (DeltaP(M)T) in response to bilateral phrenic nerve stimulation to quantify the
      onset of diaphragm fatigue. Six healthy male subjects performed four randomly
      assigned trials of identical duration (8 +/- 2 min) and breathing pattern [20
      breaths/min and time spent on inspiration during the duty cycle (time spent on
      inspiration/total time of one breathing cycle) was 0.4] during which they
      inspired primarily with the diaphragm. For trials 1-3, inspiratory resistance and
      effort was gradually increased [30, 40, and 50% maximal inspiratory pressure
      (MIP)], diaphragm fatigue did not occur, and Q(L), limb vascular resistance
      (LVR), and mean arterial pressure remained unchanged from control (P > 0.05). The
      fourth trial utilized the same breathing pattern with 60% MIP and caused
      diaphragm fatigue, as shown by a 30 +/- 12% reduction in P(M)T with bilateral
      phrenic nerve stimulation. During the fatigue trial, Q(L) and LVR were unchanged
      from baseline at minute 1, but LVR rose 36% and Q(L) fell 25% at minute 2 and by
      52% and 30%, respectively, during the final minutes of the trial. Both LVR and
      Q(L) returned to control within 30 s of recovery. In summary, voluntary increases
      in inspiratory muscle effort, in the absence of fatigue, had no effect on LVR and
      Q(L), whereas fatiguing the diaphragm elicited time-dependent increases in LVR
      and decreases in Q(L). We attribute the limb vasoconstriction to a metaboreflex
      originating in the diaphragm, which reaches its threshold for activation during
      fatiguing contractions.

PMID- 11959639
TI  - Pressure-volume-based single-beat estimations cannot predict left ventricular
      contractility in vivo.
AB  - The end-systolic pressure-volume relationship is regarded as a useful index for
      assessing the contractile state of the heart. However, the need for preload
      alterations has been a serious limitation to its clinical applications, and there
      have been numerous attempts to develop a method for calculating contractility
      based on one single pressure-volume loop. We have evaluated four of these
      methods. Pressure-volume data were obtained by combined pressure and conductance
      catheters in 37 pigs. All four methods were applied to 88 steady-state pressure
      volume files, including eight files sampled during dopamine infusions. Estimates
      of single-beat contractility (elastance) were compared with preload-varied
      multiple-beat elastance [E(es(MB))]. All methods had a low average bias (-0.3 to
      0.5 mmHg/ml) but limits of agreement (+/-2 SD) were unacceptably high (+/-2.6 to
      +/-3.8 mmHg/ml). In the dopamine group, E(es(MB)) showed an increase of 1.7 +/-
      0.8 mmHg/ml (mean +/- SD) compared with baseline (P < 0.001). None of the single
      beat methods predicted this increase in contractility. It is therefore doubtful
      whether any of the methods allow for single-beat assessment of contractility.

PMID- 11959640
TI  - Heart rate dynamics in monoamine oxidase-A- and -B-deficient mice.
AB  - Heart rate (HR) dynamics were investigated in mice deficient in monoamine oxidase
      A and B, whose phenotype includes elevated tissue levels of norepinephrine,
      serotonin, dopamine, and phenylethylamine. In their home cages, spectral analysis
      of R-R intervals revealed more pronounced fluctuations at all frequencies in the
      mutants compared with wild-type controls, with a particular enhancement at 1-4
      Hz. No significant genotypic differences in HR variability (HRV) or entropies
      calculated from Poincare plots of the R-R intervals were noted. During exposure
      to the stress of a novel environment, HR increased and HRV decreased in both
      genotypes. However, mutants, unlike controls, demonstrated a rapid return to
      baseline HR during the 10-min exposure. Such modulation may result from an
      enhanced vagal tone, as suggested by the observation that mutants responded to
      cholinergic blockade with a decrease in HRV and a prolonged tachycardia greater
      than controls. Monoamine oxidase-deficient mice may represent a useful
      experimental model for studying compensatory mechanisms responsible for changes
      in HR dynamics in chronic states of high sympathetic tone.

PMID- 11959641
TI  - Increases in endothelial Ca(2+) activate K(Ca) channels and elicit EDHF-type
      arteriolar dilation via gap junctions.
AB  - In skeletal muscle arterioles, the pathway leading to non-nitric oxide (NO), non
      prostaglandin-mediated endothelium-derived hyperpolarizing factor (EDHF)-type
      dilations is not well characterized. To elucidate some of the steps in this
      process, simultaneous changes in endothelial intracellular Ca(2+) concentration
      ([Ca(2+)](i)) and the diameter of rat gracilis muscle arterioles (approximately
      60 microm) to acetylcholine (ACh) were measured by fura 2 microfluorimetry (in
      the absence of NO and prostaglandins). ACh elicited rapid increases in
      endothelial [Ca(2+)](i) (101 +/- 7%), followed by substantial dilations (73 +/-
      2%, coupling time: 1.3 +/- 0.2 s) that were prevented by endothelial loading of
      an intracellular Ca(2+) chelator [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid]. Arteriolar dilations to ACh were also inhibited by
      intraluminal administration of the Ca(2+)-activated K(+) (K(Ca)) channel blockers
      charybdotoxin plus apamin or by palmitoleic acid, an uncoupler of myoendothelial
      gap junctions without affecting changes in endothelial [Ca(2+)](i). The presence
      of large conductance K(Ca) channels on arteriolar endothelial cells was
      demonstrated with immunohistochemisty. We propose that in skeletal muscle
      arterioles, EDHF-type mediation is evoked by an increase in endothelial
      [Ca(2+)](i), which by activating endothelial K(Ca) channels elicits
      hyperpolarization that is conducted via myoendothelial gap junctions to the
      smooth muscle resulting in decreases in [Ca(2+)](i) and consequently dilation.

PMID- 11959642
TI  - Sequential opening of IP(3)-sensitive Ca(2+) channels and SOC during alpha
      adrenergic activation of rabbit vena cava.
AB  - Alpha(1)-aderenoceptor-mediated constriction of rabbit inferior vena cava (IVC)
      is signaled by asynchronous wavelike Ca(2+) oscillations in the in situ smooth
      muscle. We have shown previously that a putative nonselective cationic channel
      (NSCC) is required for these oscillations. In this report, we show that the
      application of 2-aminoethoxyphenyl borate (2-APB) to antagonize inositol 1,4,5
      trisphosphate (InsP(3))-sensitive Ca(2+) release channels (IP(3)R channels) can
      prevent the initiation and abolish ongoing alpha(1)-aderenoceptor-mediated tonic
      constriction of the venous smooth muscle by inhibiting the generation of these
      intracellular Ca(2+) concentration ([Ca(2+)](i)) oscillations. The observed
      effects of 2-APB can only be attributed to its selective inhibition on the IP(3)R
      channels, not to its slight inhibition of the L-type voltage-gated Ca(2+) channel
      and the sarco(endo)plasmic reticulum Ca(2+) ATPase. Furthermore, 2-APB had no
      effect on the ryanodine-sensitive Ca(2+) release channel and the store-operated
      channel (SOC) in the IVC. These results indicate that the putative NSCC involved
      in refilling the sarcoplasmic reticulum (SR) and maintaining the tonic
      contraction is most likely an SOC-type channel because it appears to be activated
      by IP(3)R-channel-mediated SR Ca(2+) release or store depletion. This is in
      accordance with its sensitivity to Ni(2+) and La(3+) (SOC blockers). More
      interestingly, RT-PCR analysis indicates that transient receptor potential (Trp1)
      mRNA is strongly expressed in the rabbit IVC. The Trp1 gene is known to encode a
      component of the store-operated NSCC. These new data suggest that the activation
      of both the IP(3)R channels and the SOC are required for PE-mediated [Ca(2+)](i)
      oscillations and constriction of the rabbit IVC.

PMID- 11959643
TI  - Oxygen radicals trigger activation of NF-kappaB and AP-1 and upregulation of ICAM
      1 in reperfused canine heart.
AB  - We investigated whether oxygen radicals generated during ischemia-reperfusion
      trigger postischemic inflammation in the heart. Closed-chest dogs underwent 90
      min coronary artery occlusion, followed by 1- or 3-h reperfusion: 10 dogs
      received the cell-permeant oxygen radical scavenger N-(2-mercaptopropionyl)
      glycine (MPG; 8 mg x kg(-1) x h(-1) intracoronary) beginning 5 min before
      reperfusion, and 9 dogs received vehicle. Blood flow (microspheres),
      intercellular adhesion molecule (ICAM)-1 protein expression
      (immunohistochemistry), ICAM-1 gene activation (Northern blotting), nuclear DNA
      binding activity of nuclear factor (NF)-kappaB and AP-1 (electrophoretic mobility
      shift assays), and neutrophil (PMN) accumulation (myeloperoxidase activity) were
      assessed in myocardial tissue samples. ICAM-1 protein expression was high in
      vascular endothelium after ischemia-reperfusion but was markedly reduced by MPG.
      MPG treatment also markedly decreased expression of ICAM-1 mRNA and tissue PMN
      accumulation. Nuclear DNA binding activities of NF-kappaB and AP-1, increased by
      ischemia-reperfusion, were both markedly decreased by MPG at 1 h of reperfusion.
      However, by 3 h, AP-1 activity was only modestly reduced by MPG and NF-kappaB
      activity was not significantly different from ischemic-reperfused controls. These
      results suggest that oxygen radicals generated in vivo during reperfusion trigger
      early activation of NF-kappaB and AP-1, resulting in upregulation of the ICAM-1
      gene in vascular endothelium and subsequent tissue accumulation of activated
      PMNs.

PMID- 11959644
TI  - Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias
      in the swine right ventricle.
AB  - We tested the hypothesis that sildenafil, singly or in combination with nitric
      oxide (NO) donors, promotes ventricular tachycardia (VT) and ventricular
      fibrillation (VF). Vulnerability to VT/VF was tested by rapid pacing in eight
      isolated normal swine right ventricles (RV). The endocardial activation was
      optically mapped, and the dynamic action potential duration (APD) restitution
      curves were constructed with metal microelectrodes. At baseline, no VT/VF could
      be induced. Sildenafil (0.2 microg/ml) or NO donor singly or in combination did
      not alter VT/VF vulnerability. However, when 2 microg/ml sildenafil was combined
      with NO donors, the incidence of VT and VF rose significantly (P < 0.01). VT with
      a single periodic wavefront was induced in five of eight RVs, and VF with
      multiple wavefronts was induced in all eight RVs. The sildenafil-NO donor pro
      VT/VF combination significantly increased the maximum slope of the APD
      restitution curve and the amplitude of the APD alternans. The pro-VT/VF effects
      of sildenafil were reversible after drug-free Tyrode solution perfusion. We
      conclude that a sildenafil (2 microg/ml) and NO donor combination increases VT/VF
      vulnerability in the normal RV by a mechanism compatible with the restitution
      hypothesis.

PMID- 11959645
TI  - Expression of human smooth muscle calponin in transgenic mice revealed with a
      bacterial artificial chromosome.
AB  - Defining regulatory elements governing cell-restricted gene expression can be
      difficult because cis-elements may reside tens of kilobases away from start
      site(s) of transcription. Artificial chromosomes, which harbor hundreds of
      kilobases of genomic DNA, preserve a large sequence landscape containing most, if
      not all, regulatory elements controlling the expression of a particular gene.
      Here, we report on the use of a bacterial artificial chromosome (BAC) to begin
      understanding the in vivo regulation of smooth muscle calponin (SM-Calp). Long
      and accurate polymerase chain reaction, sequencing, and in silico analyses
      facilitated the complete sequence annotation of a BAC harboring human SM-Calp
      (hSM-Calp). RNase protection, in situ hybridization, Western blotting, and
      immunohistochemistry assays showed the BAC clone faithfully expressed hSM-Calp in
      both cultured cells and transgenic mice. Moreover, expression of hSM-Calp
      mirrored that of endogenous mouse SM-Calp suggesting that all cis-regulatory
      elements governing hSM-Calp expression in vivo were contained within the BAC.
      These BAC mice represent a new model system in which to systematically assess
      regulatory elements governing SM-Calp transcription in vivo.

PMID- 11959646
TI  - Decrease in cardiac output and muscle sympathetic activity during vasovagal
      syncope.
AB  - The importance of cardiac output (CO) to blood pressure level during vasovagal
      syncope is unknown. We measured thermodilution CO, mean blood pressure (MBP), and
      leg muscle mean sympathetic nerve activity (MSNA) each minute during 60 degrees
      head-up tilt in 26 patients with recurrent syncope. Eight patients tolerated tilt
      (TT) for 45 min (mean age 60 +/- 5 yr) and 15 patients developed syncope during
      tilt (TS) (mean age 58 +/- 4 yr, mean tilt time 15.4 +/- 2 min). In TT patients,
      CO decreased during the first minute of tilt (from 3.2 +/- 0.2 to 2.5 +/- 0.3 l x
      min(-1) x m(-2), P = 0.001) and thereafter remained stable between 2.5 +/- 0.3 (P
      = 0.001) and 2.4 +/- 0.2 l x min(-1) x m(-2) (P = 0.004) at 5 and 45 min,
      respectively. In TS patients, CO decreased during the first minute (from 3.3 +/-
      0.2 to 2.7 +/- 0.1 l x min(-1) x m(-2), P = 0.02) and was stable until 7 min
      before syncope, falling to 2.0 +/- 0.2 at syncope (P = 0.001). Regression slopes
      for CO versus time during tilt were -0.01 min(-1) in TT versus -0.1 l x min(-1) x
      m(-2) x min(-1) in TS (P = 0.001). However, MBP was more closely correlated to
      total peripheral resistance (R = 0.56, P = 0.001) and MSNA (R = 0.58, P = 0.001)
      than CO (R = 0.32, P = 0.001). In vasovagal reactions, a progressive decline in
      CO may contribute to hypotension some minutes before syncope occurs.

PMID- 11959647
TI  - Complementary role of extracellular ATP and adenosine in ischemic preconditioning
      in the rat heart.
AB  - Although adenosine is an important mediator of ischemic preconditioning (IPC),
      its relative contribution to IPC remains unknown. Because adenosine is formed
      through the hydrolysis of ATP, the present study investigated the role of ATP and
      adenosine in IPC. Isolated and buffer-perfused rat hearts underwent IPC by three
      cycles of 5-min ischemia and 5-min reperfusion before 25 min of global ischemia.
      The rate-pressure product (RPP) 30 min after reperfusion was taken as an endpoint
      of functional protection. Interstitial fluid (ISF) adenine nucleotides and
      adenosine were measured by cardiac microdialysis techniques. Inhibition of IPC
      induced recovery of RPP was partial by the adenosine receptor antagonist 8-(p
      sulfophenyl)theophylline (SPT; 100 microM) or by the structurally distinct P2Y
      purinoceptor antagonists suramin (300 microM) or reactive blue (RB; 10 microM)
      but was additive when SPT was given with suramin or RB. The P2X antagonist
      pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid tetrasodium (50 microM) had
      no effect on functional protection. The improved functional recovery was not
      significantly affected by an ecto-5'-nucleotidase inhibitor, alpha,beta-methylene
      adenosine diphosphate (AMP-CP; 100 microM), alone but was inhibited by AMP-CP
      plus SPT, suramin, or RB. ISF ATP and adenosine increased temporarily by 10-fold
      during IPC. AMP-CP augmented the increase in ISF ATP associated with the decrease
      in ISF adenosine. There was a reciprocal correlation between the ISF
      concentration of ATP and adenosine in preconditioned hearts. In addition, there
      was a significant correlation between ISF adenosine and ATP and the inhibitory
      potency of SPT and suramin or RB against functional protection conferred by IPC.
      These results suggest that extracellular ATP and adenosine play a complementary
      role in IPC through P2Y purinoceptors and adenosine receptors, respectively.

PMID- 11959648
TI  - Copper-induced vascular endothelial growth factor expression and wound healing.
AB  - Angiogenesis plays a central role in wound healing. Among many known growth
      factors, vascular endothelial growth factor (VEGF) is believed to be the most
      prevalent, efficacious, and long-term signal that is known to stimulate
      angiogenesis in wounds. Whereas a direct role of copper to facilitate
      angiogenesis has been evident two decades ago, the specific targets of copper
      action remained unclear. This report presents first evidence showing that
      inducible VEGF expression is sensitive to copper and that the angiogenic
      potential of copper may be harnessed to accelerate dermal wound contraction and
      closure. At physiologically relevant concentrations, copper sulfate induced VEGF
      expression in primary as well as transformed human keratinocytes. Copper shared
      some of the pathways utilized by hypoxia to regulate VEGF expression. Topical
      copper sulfate accelerated closure of excisional murine dermal wound allowed to
      heal by secondary intention. Copper-sensitive pathways regulate key mediators of
      wound healing such as angiogenesis and extracellular matrix remodeling. Copper
      based therapeutics represents a feasible approach to promote dermal wound
      healing.

PMID- 11959649
TI  - Serotonin 5-HT(3) receptors on mechanosensitive neurons with cardiac afferents.
AB  - In rats, the mechanosensitive cardiorenal baroreflex influencing renal excretory
      function might be impaired by serotonin occurring in coronary arteries, e.g., in
      hypertension. Because the afferent limb of this reflex could be affected, we
      investigated the responses of nodose ganglion cells (one neuron of reflex) to
      osmotic, mechanical stress in presence or absence of the serotonin 5-HT(3)
      receptor agonist phenylbiguanide (PBG). Current-voltage relationships (from -100
      to +50 mV) were obtained using cell patch recordings while the cells were exposed
      to control or hypoosmotic solutions to induce mechanical stress. This protocol
      was repeated after low doses of PBG (10 microM), angiotensin II (10 nM), or the
      stretch-activated channel blocker gadolinium (20 microM) were added to the
      extracellular medium (EM). Hypoosmotic EM induced significant changes in cellular
      conductance. The full-range current-voltage relationship allowed for the
      calculation of a mean reversal potential of -13 +/- 1.2 mV with respect to this
      change in cellular conductance (n = 44). This increase in conductance was
      impaired after addition of either PBG or gadolinium to the EM,which was
      statistically evaluated at a voltage of -80 mV, where influences of voltage-gated
      channels are not likely to interfere with the responses recorded. The serotonin 5
      HT(3) receptor antagonist tropisetron (10 nM) prevented the PBG effect on
      conductance responses. Angiotensin II had no influence. Hence, serotonin might
      decrease the mechanical sensitivity of afferent cardiac nerves controlling renal
      sympathetic nerve activity.

PMID- 11959650
TI  - Gene transfer of Cu/Zn SOD to cerebral vessels prevents FPI-induced CBF
      autoregulatory dysfunction.
AB  - The goal of this study was to determine whether gene transfer of human copper
      zinc (Cu/Zn) superoxide dismutase (SOD) has preventive effects on cerebral blood
      flow (CBF) autoregulatory dysfunction after fluid percussion injury (FPI). Rats
      subjected to FPI (2-2.5 atm) exhibited enhanced activity of reduced NADP (NADPH)
      oxidase in the cerebral vasculature. In line with these findings, the rats showed
      not only reduced vasodilation of the pial artery in response to calcitonin gene
      related peptide and levcromakalim but also impaired autoregulatory vasodilation
      in response to acute hypotension. The FPI-induced hemodynamic alterations were
      significantly prevented by pretreatment with diphenyleneiodonium (10 micromol/l),
      an NAD(P)H oxidase inhibitor. Intracisternal application of recombinant
      adenovirus (100 microl of 1 x 10(10) pfu/ml)-encoding human Cu/Zn SOD 3 days
      before FPI prevented the impairment of vasodilation to hypotension and
      vasorelaxants, resulting in the restoration of CBF autoregulation. Our findings
      demonstrate that FPI-induced impairment of CBF autoregulation is closely related
      with NAD(P)H oxidase-derived superoxide anion, and these alterations can be
      prevented by the recombinant adenovirus-mediated transfer of human Cu/Zn SOD gene
      to the cerebral vasculature.

PMID- 11959651
TI  - Effects of aging on vasoconstrictor and mechanical properties of rat skeletal
      muscle arterioles.
AB  - Exercise capacity and skeletal muscle blood flow during exercise are reduced with
      advancing age. This reduction in blood flow capacity may be related to increased
      reactivity of skeletal muscle resistance vessels to vasoconstrictor stimuli. The
      purpose of this study was to test the hypothesis that aging results in increased
      vasoconstrictor responses of skeletal muscle resistance arterioles. First-order
      (1A) arterioles (90-220 microm) from the gastrocnemius and soleus muscles of
      young (4 mo) and aged (24 mo) Fischer-344 rats were isolated, cannulated, and
      pressurized via hydrostatic reservoirs. Vasoconstriction in response to increases
      in norepinephrine (NE; 1 x 10(-9)-1 x 10(-4) M) and KCl (20-100 mM)
      concentrations and increases in intraluminal pressure (10-130 cmH(2)O) were
      evaluated in the absence of flow. Responses to NE and KCl were similar in both
      soleus and gastrocnemius muscle arterioles from young and aged rats. In contrast,
      active myogenic responses to changes in intraluminal pressure were diminished in
      soleus and gastrocnemius arterioles from aged rats. To assess whether alterations
      in the mechanical properties of resistance arterioles underlie altered myogenic
      responsiveness, passive diameter responses to pressure and mechanical stiffness
      were evaluated. There was no effect of age on the structural behavior (passive
      pressure-diameter relationship) or stiffness of arterioles from either the soleus
      or gastrocnemius muscles. These results suggest that aging does not result in a
      nonspecific decrease in vasoconstrictor responsiveness of skeletal muscle
      arterioles. Rather, aging-induced adaptations of vasoreactivity of resistance
      arterioles appear to be limited to mechanisms that are uniquely involved in the
      signaling of the myogenic response.

PMID- 11959652
TI  - Calcium- and superoxide anion-mediated mitogenic action of substance P on cardiac
      fibroblasts.
AB  - Substance P is released from nerve endings in the heart under pathological
      conditions like ischemia, but its action on cardiac cells has not been
      investigated. This study tested the hypothesis that substance P is mitogenic to
      adult cardiac fibroblasts and delineated the underlying mechanism(s). Substance
      P, acting via neurokinin-1 (NK-1) receptors, stimulated cellular hyperplasia over
      a range of 1-10 micromol/l. It elicited no change in net collagen production,
      total protein synthesis, or cell protein content but increased (45)Ca uptake and
      superoxide generation. EGTA, N-acetyl-cysteine, and superoxide dismutase
      attenuated the hyperplastic response to substance P. A combination of substance P
      and EGTA enhanced superoxide generation without an increase in DNA synthesis,
      showing that an increase in superoxide production does not result in hyperplasia
      when extracellular Ca(2+) is chelated. Together, the data suggest that substance
      P may activate, via NK-1 receptors, a hyperplastic but not hypertrophic response
      in adult cardiac fibroblasts and that alterations in redox state and Ca(2+)
      homeostasis may act in concert to mediate its mitogenic action.

PMID- 11959653
TI  - Pharmacological correction of hypothermic P(50) shift does not alter outcome from
      focal cerebral ischemia in rats.
AB  - Hypothermia decreases the arterial PO(2) at which hemoglobin is 50% saturated
      (P(50)), increasing hemoglobin O(2)-binding affinity. We used RSR13, a synthetic
      allosteric modifier of hemoglobin that increases P(50), to study the role of
      altered hemoglobin O(2)-binding affinity in mild hypothermic neuroprotection.
      RSR13 (150 mg/kg iv) restored P(50) to normothermic values. Rats underwent 70 min
      of middle cerebral artery occlusion (MCAO) at 30.0, 34.0, or 37.5 degrees C with
      hemoglobin saturation held at 98-100%. The 34.0 degrees C group received RSR13 or
      vehicle before ischemia. After 7 days of recovery, infarct volumes were reduced
      in all hypothermic groups, without evidence of a detrimental effect on infarct
      size or neurological score as a result of P(50) correction. To examine for a
      beneficial effect of P(50) correction, ischemia duration was increased to 120 min
      in rats maintained at 34.0 degrees C. Correction of P(50) by RSR13 did not alter
      cerebral infarct sizes or neurological scores. The decrease in P(50), caused by
      mild hypothermia, could not be associated with infarct size or neurological
      deficit resulting from ischemic brain hypoxia in rats.

PMID- 11959654
TI  - Increased nonoxidative glycolysis despite continued fatty acid uptake during
      demand-induced myocardial ischemia.
AB  - During stress, patients with coronary artery disease frequently fail to increase
      coronary flow and myocardial oxygen consumption (MVO(2)) in response to a greater
      demand for oxygen, resulting in "demand-induced" ischemia. We tested the
      hypothesis that dobutamine infusion with flow restriction stimulates nonoxidative
      glycolysis without a change in MVO(2) or fatty acid uptake. Measurements were
      made in the anterior wall of anesthetized open-chest swine hearts (n = 7). The
      left anterior descending (LAD) coronary artery flow was controlled via an
      extracorporeal perfusion circuit, and substrate uptake and oxidation were
      measured with radiotracers. Demand-induced ischemia was produced with intravenous
      dobutamine (15 microg x kg(-1) x min(-1)) and 20% reduction in LAD flow for 20
      min. Despite no change in MVO(2), there was a switch from lactate uptake (5.9 +/-
      3.1) to production (74.5 +/- 16.3 micromol/min), glycogen depletion (66%), and
      increased glucose uptake (105%), but no change in anterior wall power or the
      index of anterior wall energy efficiency. There was no change in the rate of
      tracer-measured fatty acid uptake; however, exogenous fatty acid oxidation
      decreased by 71%. Thus demand-induced ischemia stimulated nonoxidative glycolysis
      and lactate production, but did not effect fatty acid uptake despite a fall in
      exogenous fatty acid oxidation.

PMID- 11959655
TI  - Channels involved in transient currents unmasked by removal of extracellular
      calcium in cardiac cells.
AB  - In cardiac cells that lack macroscopic transient outward K(+) currents (I(to)),
      the removal of extracellular Ca(2+) can unmask "I(to)-like" currents. With the
      use of pig ventricular myocytes and the whole cell patch-clamp technique, we
      examined the possibility that cation efflux via L-type Ca(2+) channels underlies
      these currents. Removal of extracellular Ca(2+) and extracellular Mg(2+) induced
      time-independent currents at all potentials and time-dependent currents at
      potentials greater than -50 mV. Either K(+) or Cs(+) could carry the time
      dependent currents, with reversal potential of +8 mV with internal K(+) and +34
      mV with Cs(+). Activation and inactivation were voltage dependent [Boltzmann
      distributions with potential of half-maximal value (V(1/2)) = -24 mV and slope = 
      9 mV for activation; V(1/2) = -58 mV and slope = 13 mV for inactivation]. The
      time-dependent currents were resistant to 4-aminopyridine and to DIDS but blocked
      by nifedipine at high concentrations (IC(50) = 2 microM) as well as by verapamil
      and diltiazem. They could be increased by BAY K-8644 or by isoproterenol. We
      conclude that the I(to)-like currents are due to monovalent cation flow through L
      type Ca(2+) channels, which in pig myocytes show low sensitivity to nifedipine.

PMID- 11959656
TI  - Sex differences in repolarization homogeneity and its circadian pattern.
AB  - The reason for sex differences in arrhythmic risk remains unclear. Heterogeneity
      of ventricular repolarization is directly linked to arrhythmogenesis; thus we
      investigated repolarization homogeneity and its circadian pattern in men and
      women. During 24-h Holter recordings in 60 healthy subjects (27 males), a 12-lead
      electrocardiogram (ECG) was obtained every 30 s. RR and QT intervals, and, after
      singular-value decomposition, two characteristics of repolarization homogeneity
      were calculated in each ECG. Corrected QT (QTc) values were obtained using an
      individually optimized heart rate (HR) correction formula. All values were
      averaged over 10-min time bands from 0000 to 2400. There were substantial sex
      differences in both global repolarization homogeneity (measured by the total
      cosine of the angle between QRS and T wave vectors) and regional homogeneity of
      repolarization (quantified independently by the relative T wave residuum).
      Whereas women throughout the 24 h followed more closely the pattern of inverse
      sequence between depolarization and repolarization, they also showed much higher
      localized repolarization heterogeneity than men. In both women and men,
      repolarization irregularity was greatest during morning hours. A sex difference
      was also observed for HR and QTc interval; however, the circadian patterns of the
      repolarization homogeneity descriptors were different from those of HR and QTc
      intervals.

PMID- 11959657
TI  - Forebrain-mediated adaptations to myocardial infarction in the rat.
AB  - Recent studies suggest that the forebrain contributes to the circulatory
      derangements leading to heart failure after myocardial injury. We tested that
      hypothesis by examining the effect of myocardial infarction (MI) or sham MI (MI
      s) on neurohumoral regulation in rats with prior anteroventral (AV) third
      ventricle lesion (AV3V-x) or sham lesion (AV3V-s). AV3V-s/MI rats had higher
      sodium intake, lower urine volume, and lower urinary sodium excretion than AV3V
      s/MI-s rats. AV3V-x/MI rats had lower sodium intake and higher urine volume than
      AV3V-s/MI or AV3V-s/MI-s rats and urinary sodium excretion comparable to AV3V
      s/MI-s rats. AV3V-x had no effect on baseline plasma renin activity (PRA). One
      week after MI, PRA had increased in AV3V-s but decreased in AV3V-x rats. AV3V-x
      reduced renal sympathetic nerve activity in MI and MI-s rats. AV3V-x improved
      baroreflex function in MI rats but diminished it in MI-s rats. Survival beyond 2
      wk was lower in the AV3V-x/MI rats than in all other groups. These results
      confirm a critical role for the forebrain in the neurohumoral adjustments to MI.

PMID- 11959658
TI  - Burn plasma mediates cardiac myocyte apoptosis via endotoxin.
AB  - Thermal trauma is associated with cardiac myocyte apoptosis in vivo. To determine
      whether cardiac myocyte apoptosis could be secondary to burn-induced cytokines or
      inflammatory mediators, we investigated the effects of tumor necrosis factor
      alpha (TNF-alpha) and burn plasma on a murine cardiac myocyte cell line and
      primary culture myocytes. HL-1 cells were exposed to plasma isolated from burned
      or sham rats. Burn, but not sham plasma, induced significant increases in caspase
      3 activity and DNA fragmentation. Similar results were obtained in primary
      culture rat myocytes. A dose-dependent increase in caspase-3 activity was
      observed when HL-1 cells were incubated with increasing concentrations of TNF
      alpha. Even though TNF-alpha increased apoptosis, enzyme-linked immunosorbent
      assay detected no TNF-alpha in burn plasma. Burn plasma also failed to induce TNF
      alpha mRNA, eliminating an autocrine mechanism of TNF-alpha secretion and
      binding. Also, treatment of burn plasma containing rhuTNFR:Fc failed to inhibit
      apoptosis. To examine the possibility that endotoxin within burn plasma might
      account for the apoptotic effect, burn plasma was preincubated with rBPI(21).
      Caspase-3 activity was reduced to control levels. These data indicate that burn
      plasma induces apoptosis in cardiac myocytes via an endotoxin-dependent mechanism
      and suggest that systemic inhibition of endotoxin may provide a therapeutic
      approach for treatment of burn-associated cardiac dysfunction.

PMID- 11959659
TI  - Action potential duration restitution and ventricular fibrillation due to rapid
      focal excitation.
AB  - The focal source hypothesis of ventricular fibrillation (VF) posits that rapid
      activation from a focal source, rather than action potential duration (APD)
      restitution properties, is responsible for the maintenance of VF. We injected
      aconitine (100 microg) into normal isolated perfused swine right ventricles (RVs)
      stained with 4-[beta-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium (di-4
      ANEPPS) for optical mapping studies. Within 97 +/- 163 s, aconitine induced
      ventricular tachycardia (VT) with a mean cycle length 268 +/- 37 ms, which
      accelerated before converting to VF. Drugs that flatten the APD restitution
      slope, including diacetyl monoxime (10-20 mM, n = 6), bretylium (10-20 microg/ml,
      n = 3), and verapamil (2-4 microg/ml, n = 3), reversibly converted VF to VT in
      all cases. In two RVs, VF persisted despite of the excision of the aconitine
      site. Simulations in two-dimensional cardiac tissue showed that once VF was
      initiated, it remained sustained even after the "aconitine" site was eliminated.
      In this model of focal source VF, the VT-to-VF transition occurred due to a wave
      break outside the aconitine site, and drugs that flattened the APD restitution
      slope converted VF to VT despite continuous activation from aconitine site.

PMID- 11959660
TI  - Del1 mediates VSMC adhesion, migration, and proliferation through interaction
      with integrin alpha(v)beta(3).
AB  - Del1 is a matrix protein transiently expressed by embryonic endothelial cells. It
      was recently demonstrated that vascular endothelial cells adhere and interact
      with Del1 through alpha(v)beta(3)- integrins, providing an autocrine angiogenic
      signaling pathway in this cell type. To determine whether Del1 might signal to
      other cell types in the vessel wall in a paracrine fashion, studies were
      conducted with vascular smooth muscle cells (VSMC). Del1 promoted adhesion and
      migration of VSMC in a dose-dependent fashion. These functions were mediated
      through alpha(v)beta(3)-integrins, as the vitronectin receptor inhibitory peptide
      containing penacillamine (PCN) arginine-glycine-aspartic acid (PCN-RGD) and an
      antibody specific for the alpha(v)beta(3)-integrin specifically blocked both
      adhesion and migration. Adhesion of VSMC to Del1 was associated with organization
      of actin filaments and formation of focal contacts enriched in vinculin and
      alpha(v)beta(3). Furthermore, Del1 supported VSMC proliferation at least in part
      by inhibiting these cells from undergoing apoptosis. These data, in conjunction
      with evidence that Del1 expression is reactivated in vascular injury, suggest
      that Del1 may have a paracrine role in vessel wall development and remodeling.

PMID- 11959661
TI  - Enhanced IPC by activation of pertussis toxin-sensitive and -insensitive G
      protein-coupled purinoceptors.
AB  - Extracellular ATP plays an important role in ischemic preconditioning (IPC)
      through the activation of P(2y) purinoceptors. This study examined whether ATP
      stimulated P(2y) purinoceptors are coupled to pertussis toxin (PTX)-insensitive G
      protein and whether activation of this pathway enhances myocardial protection
      afforded by IPC. The rat was treated with PTX for 48 h, and the heart was then
      isolated and buffer perfused. The heart underwent IPC by three cycles of 5-min
      ischemia and 5-min reperfusion before 25 min of global ischemia. Isovolumic left
      ventricular function was measured, and functional recovery at 30 min after
      reperfusion was taken as an end point of myocardial protection. PTX pretreatment
      partially inhibited functional protection by IPC. Treatment with 100 microM 8-(p
      sulfophenyl) theophylline (SPT) during IPC had no further effect on PTX-induced
      inhibition of functional protection by IPC, whereas suramin (300 microM) or
      reactive blue (RB) (10 microM) completely abolished myocardial protection in the
      preconditioned heart pretreated with PTX. Supplementation with adenosine (30
      microM), ATP (30 microM), or UTP (50 microM) significantly enhanced IPC-induced
      functional protection, although preconditioning with these nucleotides without
      IPC had no protective effect. Adenosine-enhanced IPC was inhibited by
      pretreatment with PTX and SPT but not by suramin or RB, whereas ATP-enhanced IPC
      was inhibited by suramin or RB in combination with PTX pretreatment. On the other
      hand, UTP-enhanced IPC was not affected by PTX pretreatment but was inhibited by
      suramin or RB. Adenosine supplemented IPC without PTX pretreatment and ATP
      supplemented IPC with PTX pretreatment were not affected by nitric oxide synthase
      inhibitor N(omega)-nitro-L-arginine methyl ester (100 microM). Although the
      protein kinase C inhibitor Ro318425 (0.3 microM) or tyrosine kinase inhibitor
      genistein (50 microM) had no significant effect on the functional protection
      afforded by adenosine-supplemented IPC without PTX pretreatment and ATP
      supplemented IPC with PTX pretreatment, the combination of Ro318425 and genistein
      attenuated functional protection afforded by both the purinoceptor agonist
      supplemented IPC. These results suggest the crucial involvement of PTX-sensitive
      and -insensitive G protein coupled purinoceptors in enhanced IPC by
      supplementation with adenosine, ATP, and UTP.

PMID- 11959663
TI  - The promise of translational physiology.

PMID- 11959662
TI  - Role of ET-1 receptor binding and [Ca(2+)](i) in contraction of coronary arteries
      from DOCA-salt hypertensive rats.
AB  - Hypertension is associated with an increase in coronary artery disease, but
      little is known about the regulation of coronary vascular tone by endothelin-1
      (ET-1) in hypertension. The present study evaluated the mechanisms mediating
      altered contraction to ET-1 in coronary small arteries from deoxycorticosterone
      acetate (DOCA)-salt hypertensive rats. DOCA-salt rats exhibited an increase in
      systolic blood pressure and plasma ET-1 levels compared with placebo rats.
      Contraction to ET-1 (1 x 10(-11) to 3 x 10(-8) M), measured in isolated coronary
      small arteries maintained at a constant intraluminal pressure of 40 mmHg, was
      largely reduced in vessels from DOCA-salt rats compared with placebo rats. To
      determine the role of endothelin receptor binding in the impaired contraction to
      ET-1, (125)I-labeled ET-1 receptor binding was measured in membranes isolated
      from coronary small arteries. Maximum binding (fmol/mg protein) and binding
      affinity were similar in coronary membranes from DOCA-salt rats compared with
      placebo rats. Changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) were
      measured in freshly dissociated coronary small artery smooth muscle cells loaded
      with fura 2. ET-1 (10(-9) M) produced a 30 +/- 9% increase in [Ca(2+)](i) in
      smooth muscle cells from placebo rats, but had no effect on cells from DOCA-salt
      rats (2 +/- 2%). In summary, the ET-1-induced coronary artery contraction and
      increase in [Ca(2+)](i) are impaired in DOCA-salt hypertensive rats, whereas
      endothelin receptor binding is not altered. These results suggest endothelin
      receptor uncoupling from signaling mechanisms and indicate that impaired
      [Ca(2+)](i) signaling contributes to the decrease in ET-1-induced contraction of
      coronary small arteries in DOCA-salt hypertensive rats.

PMID- 11959664
TI  - What is written, read, and cited in AJP-regulatory, integrative and comparative
      physiology?

PMID- 11959665
TI  - Regulation of body weight.

PMID- 11959666
TI  - The use of microcomputed tomography to study microvasculature in small rodents.
AB  - Appropriate nephron function is dependent on the intrarenal arrangement of blood
      vessels. The preferred and primary means to study the architecture of intrarenal
      circulation has been by filling it with opaque substances such as india ink,
      radio-opaque contrast material, or various polymers for study by light or
      scanning electron microscopy. With such methodologies, superficial vessels may
      obscure deep vessels and little quantitative information may be obtained. Serial
      section microtomy has not been practical because of problems relating to
      alignment and registration of adjacent sections, lost sections, and preparation
      time and effort. Microcomputed tomography (micro-CT) overcomes such limitations
      and provides a means to study the three-dimensional architecture of filled
      vessels within an intact rodent kidney and to obtain more quantitative
      information. As an example of micro-CT's capabilities, we review the use of micro
      CT to study the alterations in renal microvasculature caused by the development
      of liver cirrhosis after chronic bile duct ligation. In this example, micro-CT
      evidence shows a selective decrease in cortical vascular filling in the kidney,
      with a maintenance of medullary vascular filling. These changes may contribute to
      the salt and water retention that accompanies cirrhosis. These results indicate
      that micro-CT is a promising method to evaluate renal vascular architecture in
      the intact rodent kidney relative to physiological and pathological function.

PMID- 11959667
TI  - Venular-arteriolar communication in the regulation of blood flow.
AB  - Muscle blood flow is regulated to meet the metabolic needs of the tissue. With
      the vasculature arranged as a successive branching of arterioles and the larger,
      >50 microm, arterioles providing the major site of resistance, an increasing
      metabolic demand requires the vasodilation of the small arterioles first then the
      vasodilation of the more proximal, larger arterioles. The mechanism(s) for the
      coordination of this ascending vasodilation are not clear and may involve a
      conducted vasodilation and/or a flow-dependent response. The close arteriolar
      venular pairing provides an additional mechanism by which the arteriolar diameter
      can be increased due to the diffusion of vasoactive substances from the venous
      blood. Evidence is presented that the venular endothelium releases a relaxing
      factor, a metabolite of arachidonic acid, that will vasodilate the adjacent
      arteriole. The stimulus for this release is not known, but it is hypothesized
      that hypoxia-induced ATP release from red blood cells may be responsible for the
      stimulation of arachidonic release from the venular endothelial cells. Thus the
      venous circulation is in an optimal position to monitor the overall metabolic
      state of the tissue and thus provide a feedback regulation of arteriolar
      diameter.

PMID- 11959668
TI  - Fat depot origin affects adipogenesis in primary cultured and cloned human
      preadipocytes.
AB  - Fat distribution varies among individuals with similar body fat content. Innate
      differences in adipose cell characteristics may contribute because lipid
      accumulation and lipogenic enzyme activities vary among preadipocytes cultured
      from different fat depots. We determined expression of the adipogenic
      transcription factors peroxisome proliferator activated receptor-gamma (PPAR
      gamma) and CCAAT/enhancer binding protein-alpha (C/EBP-alpha) and their targets
      in abdominal subcutaneous, mesenteric, and omental preadipocytes cultured in
      parallel from obese subjects. Subcutaneous preadipocytes, which had the highest
      lipid accumulation, glycerol-3-phosphate dehydrogenase (G3PD) activity, and
      adipocyte fatty acid binding protein (aP2) abundance, had highest PPAR-gamma and
      C/EBP-alpha expression. Levels were intermediate in mesenteric and lowest in
      omental preadipocytes. Overexpression of C/EBP-alpha in transfected omental
      preadipocytes enhanced differentiation. The proportion of differentiated cells in
      colonies derived from single subcutaneous preadipocytes was higher than in
      mesenteric or omental clones. Only cells that acquired lipid inclusions exhibited
      C/EBP-alpha upregulation, irrespective of depot origin. Thus regional variation
      in adipogenesis depends on differences at the level of transcription factor
      expression and is a trait conferred on daughter cells.

PMID- 11959669
TI  - Two nitridergic peptides are encoded by the gene capability in Drosophila
      melanogaster.
AB  - A Drosophila gene (capability, capa) at 99D on chromosome 3R potentially encodes
      three neuropeptides: GANMGLYAFPRV-amide (capa-1), ASGLVAFPRV-amide (capa-2), and
      TGPSASSGLWGPRL-amide (capa-3). Capa-1 and capa-2 are related to the lepidopteran
      hormone cardioacceleratory peptide 2b, while capa-3 is a novel member of the
      pheromone biosynthesis-activating neuropeptide/diapause hormone/pyrokinin family.
      By immunocytochemistry, we identified four pairs of neuroendocrine cells likely
      to release the capa peptides into the hemolymph: one pair in the subesophageal
      ganglion and the other three in the abdominal neuromeres. In the Malpighian
      (renal) tubule, capa-1 and capa-2 increase fluid secretion rates, stimulate
      nitric oxide production, and elevate intracellular Ca(2+) and cGMP in principal
      cells. Capa-stimulated fluid secretion, but not intracellular Ca(2+)
      concentration rise, is inhibited by the guanylate cyclase inhibitor methylene
      blue. The actions of capa-1 and capa-2 are not synergistic, implying that both
      act on the same pathways in tubules. The capa gene is thus the first to be shown
      to encode neuropeptides that act on renal fluid production through nitric oxide.

PMID- 11959670
TI  - Transepithelial organic anion transport by shark choroid plexus.
AB  - Spiny dogfish shark (Squalus acanthias) lateral and IV choroid plexuses (CPs) are
      ultrastructurally similar to the corresponding tissues of rat. However, shark IV
      CP is proportionally larger and easily accessible. Moreover, this epithelial
      sheet can be halved and studied in Ussing flux chambers. We have used confocal
      fluorescence microscopy and radiotracer techniques to characterize
      transepithelial transport of the organic anions (OAs) fluorescein (FL) and 2,4
      dichlorophenoxyacetic acid (2,4-D), respectively, by shark CP. Lateral and IV CP
      accumulated 1 microM FL, with highest levels in the underlying extracellular
      spaces, intermediate levels in epithelial cells, and lowest levels in the medium.
      2,4-D and probenecid inhibited FL accumulation in cells and extracellular spaces,
      suggesting that these substrates compete for common carriers. Unidirectional
      absorptive [cerebrospinal fluid (CSF)-to-blood] and secretory (blood-to-CSF)
      fluxes of 10 microM [(14)C]2,4-D were measured under short-circuited conditions
      in IV CP mounted in Ussing chambers. 2,4-D underwent net absorption, with an
      average flux ratio of 7. Probenecid, 2,4,5-trichlorophenoxyacetic acid, and 5
      hydroxyindolacetic acid reduced net absorption, reversibly inhibiting
      unidirectional absorption, with no effect on secretion. Ouabain irreversibly
      reduced net 2,4-D absorption and cellular and extracellular accumulation of FL,
      suggesting energetic coupling of OA absorption to Na(+) transport. Collectively,
      these data indicate that shark CP actively removes OAs from CSF by a process that
      is specific and active.

PMID- 11959671
TI  - Mechanisms for maintaining extracellular glutamate levels in the anoxic turtle
      striatum.
AB  - The turtle Trachemys scripta is one of a limited group of vertebrates that can
      withstand hours to days without oxygen. One facet of anoxic survival is the
      turtle's ability to maintain basal extracellular glutamate levels, whereas in
      most vertebrates, anoxia triggers massive excitotoxic glutamate release. We
      investigated glutamate release and reuptake in the anoxic turtle and the effects
      of adenosine and ATP-sensitive potassium (K(ATP)) channels on glutamate
      homeostasis. Striatal extracellular glutamate was measured in anesthetized T.
      scripta by microdialysis in normoxia and over 2-h anoxia. Glutamate release is
      decreased by 44% in the early anoxic turtle; this anoxia-induced decrease in
      glutamate release was prevented when K(ATP) channels and adenosine receptors were
      blocked simultaneously but not when either mechanism was blocked individually. We
      hypothesize that the continued release and reuptake of glutamate during anoxia
      help maintain neuronal tone and aid in the recovery of a functional neuronal
      network after long periods of anoxia, whereas activation of adenosine and/or
      K(ATP) conserves energy by reducing glutamate release and lowering transport
      costs.

PMID- 11959672
TI  - Inhibiting adenosine deaminase modulates the systemic inflammatory response
      syndrome in endotoxemia and sepsis.
AB  - By pharmacological manipulation of endogenous adenosine, using chemically
      distinct methods, we tested the hypothesis that endogenous adenosine tempers
      proinflammatory cytokine responses and oxyradical-mediated tissue damage during
      endotoxemia and sepsis. Rats were pretreated with varying doses of pentostatin
      (PNT; adenosine deaminase inhibitor) or 8-sulfophenyltheophylline (8-SPT;
      adenosine receptor antagonist) and then received either E. coli endotoxin
      (lipopolysaccharide; 0.01 or 2.0 mg/kg) or a slurry of cecal matter in 5%
      dextrose in water (200 mg/kg). Resultant levels of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-1beta, and IL-10 were measured in serum and in liver and
      spleen. Untreated, 2 mg/kg lipopolysaccharide elevated serum TNF-alpha, IL-1beta,
      and IL-10. PNT dose dependently attenuated, without ablating, the elevation in
      serum TNF-alpha and IL-1beta and raised liver and spleen IL-10. PNT also
      attenuated elevation of TNF-alpha in serum, liver, and spleen at 4 and 24 h after
      sepsis induction, and 8-SPT resulted in higher proinflammatory cytokines.
      Modulating endogenous adenosine was also effective in exacerbated (8-SPT) or
      diminished (PNT) tissue peroxidation. Survival from sepsis was also improved when
      PNT was used as a posttreatment. These data indicate that endogenous adenosine is
      an important modulatory component of systemic inflammatory response syndromes.
      These data also indicate that inhibition of adenosine deaminase may be a novel
      and viable therapeutic approach to managing the systemic inflammatory response
      syndrome without ablating important physiological functions.

PMID- 11959673
TI  - Cardiovascular alterations and autonomic imbalance in an experimental model of
      depression.
AB  - Depressed patients with and without a history of cardiovascular pathology display
      signs, such as elevated heart rate, decreased heart rate variability, and
      increased physiological reactivity to environmental stressors, which may indicate
      a predisposition to cardiovascular disease. The specific physiological mechanisms
      associating depression with such altered cardiovascular parameters are presently
      unclear. The current study investigated cardiovascular regulation in the chronic
      mild stress rodent model of depression and examined the specific autonomic
      nervous system mechanisms underlying the responses. Sprague-Dawley rats exposed
      to a series of mild, unpredictable stressors over 4 wk displayed anhedonia (an
      essential feature of human depression), along with elevated resting heart rate,
      decreased heart rate variability, and exaggerated pressor and heart rate
      responses to air jet stress. Results obtained from experiments studying autonomic
      blockade suggest that cardiovascular alterations in the chronic mild stress model
      are mediated by elevated sympathetic tone to the heart. The present findings have
      implications for the study of pathophysiological links between affective
      disorders and cardiovascular disease.

PMID- 11959674
TI  - Pharyngeal branch of the glossopharyngeal nerve plays a major role in reflex
      swallowing from the pharynx.
AB  - Mechanical stimulation of the pharyngeal areas readily elicits reflex swallowing.
      However, it is much more difficult for electrical stimulation of the
      glossopharyngeal nerve (GPN) to evoke reflex swallowing than it is for
      stimulation of the superior laryngeal nerve (SLN) to do so. These paradoxical
      findings remain unexplained; hence, the main purpose of this study was to explain
      this contradiction by using a urethane-anesthetized rat. Mechanical stimulation
      easily elicited reflex swallowing from the pharynx. The posterior pillars,
      posterior pharyngeal wall, and the soft palate of the rat were extremely
      reflexogenic areas for swallowing. Sectioning the pharyngeal branch of the GPN
      (GPN-ph), however, eliminated the swallowing reflex from these areas. In
      contrast, sectioning the lingual branch of the GPN had no effect on the
      elicitation of swallowing. Electrical stimulation of the GPN-ph and SLN elicited
      sequentially occurring swallows. The relationship between stimulus frequency and
      the latency of swallowing for the GPN-ph was approximately the same as that for
      the SLN. These results indicate that the GPN-ph plays a major role in the
      initiation of reflex swallowing from the pharynx in rats.

PMID- 11959675
TI  - HPA-axis responses during experimental colitis in the rat.
AB  - We investigated the responses of the hypothalamic-pituitary-adrenal (HPA) axis
      during experimental colitis induced by intracolonic administration of 2,4,6
      trinitrobenzenesulfonic acid in the rat. On days 3 and 7 after induction of
      colitis, the corticotropin-releasing hormone (CRH) mRNA level in the
      parvocellular paraventricular nucleus (pPVN) of the hypothalamus was reduced, the
      plasma ACTH level remained at the basal level, and the plasma corticosterone
      (Cort) level was high. Induction of colitis on day 3 after adrenalectomy with
      Cort pellet replacement (ADX + Cort) resulted in a marked increase in CRH mRNA on
      day 7 after induction of colitis compared with noncolitic ADX + Cort animals.
      Pair feeding to match the food intake of the colitic animals resulted in no
      significant change in CRH mRNA in the pPVN, plasma ACTH, and Cort compared with
      healthy control animals. These findings indicated that CRH mRNA expression in the
      pPVN was inhibited by glucocorticoid feedback during this experimental colitis,
      and the decrease in food intake during colitis was not simply responsible for the
      expression of CRH mRNA. It is inferred that the HPA axis including the CRH level
      in the pPVN is altered in patients with inflammatory bowel disease.

PMID- 11959676
TI  - beta-Adrenergic modulation of muscarinic cholinergic receptor expression and
      function in developing heart.
AB  - Imbalances of beta-adrenoceptor (beta-AR) and muscarinic ACh receptor (mAChR)
      input are thought to underlie perinatal cardiovascular abnormalities in
      conditions such as sudden infant death syndrome. Administration of isoproterenol,
      a beta(1)/beta(2)-AR agonist, to neonatal rats on postnatal days (PN) 2-5 caused
      downregulation of cardiac m(2)AChRs and a corresponding decrement in their
      control of adenylyl cyclase activity. Terbutaline, a beta(2)-selective agonist
      that crosses the placenta and the blood-brain barrier, was also effective when
      given either on PN 2-5 or during gestational days 17-20. Terbutaline failed to
      downregulate brain m(2)AChRs, even though it downregulated beta-ARs; beta-ARs and
      m(2)AChRs are located on different cell populations in the brain, but they are on
      the same cells in the heart. Destruction of catecholaminergic neurons with
      neonatal 6-hydroxydopamine upregulated cardiac but not brain m(2)AChRs. These
      results suggest that perinatal beta-AR stimulation shifts cardiac receptor
      production away from the generation of m(2)AChRs so that the development of
      sympathetic innervation acts as a negative modulator of cholinergic function.
      Accordingly, tocolytic therapy with beta-AR agonists may compromise the perinatal
      balance of adrenergic and cholinergic inputs.

PMID- 11959677
TI  - NOS inhibition restores renal responses to atrial distension during pregnancy.
AB  - Nitric oxide (NO) biosynthesis increases during pregnancy and has been shown to
      suppress baroreceptor activity. The renal response to a simulated increase in
      circulating blood volume (atrial distension) is also attenuated at this time. We
      hypothesized that blocking NO biosynthesis during pregnancy would restore the
      renal response. Female rats were implanted with indwelling intracardiac balloons
      and central venous cannulas. After recovery, they were mated, and on day 14 of
      pregnancy, osmotic minipumps containing the NO synthase inhibitor N(G)-nitro-L
      arginine methyl ester (L-NAME) or its inactive enantiomer N(G)-nitro-D-arginine
      methyl ester (D-NAME) (120 mg/2 ml at 10 microg/min) were implanted. In response
      to atrial distension (1 h), urine output increased in the D- and L-NAME-treated
      virgin rats. During pregnancy (day 20), this response was attenuated in the D
      NAME-treated, but not the L-NAME-treated, animals, i.e., after a simulated
      increase in circulating blood volume, inhibition of NO biosynthesis restored the
      renal response of pregnant rats to that seen in virgin animals. We conclude that,
      during normal pregnancy, increased NO biosynthesis blunts the reflex renal
      response to atrial distension.

PMID- 11959678
TI  - Daily CCK injection enhances reduction of body weight by chronic
      intracerebroventricular leptin infusion.
AB  - In the present study, we tested the hypothesis that a single daily injection of
      the gut peptide CCK, together with continuous leptin infusion, would produce
      significantly greater loss of body weight than leptin alone. We found that a
      single daily intraperitoneal injection of CCK-8 (0.5 microg/kg) significantly
      enhanced the weight-reducing effects of 0.5 microg/day leptin infused
      continuously into the lateral ventricle of male Sprague-Dawley rats by osmotic
      minipump. However, CCK and leptin together did not enhance reduction of daily
      chow intake. Furthermore, there was no synergistic reduction of 30-min sucrose
      intake, although a significant main effect of both leptin and CCK was observed on
      sucrose intake. These results 1) confirm our previous reports of synergy between
      leptin and CCK on body weight, 2) demonstrate that enhancement of leptin-induced
      weight loss does not require bolus administration of leptin, and 3) suggest that
      enhanced body weight loss following leptin and CCK does not require synergistic
      reduction of food intake by leptin and CCK.

PMID- 11959679
TI  - Accelerated recovery after endotoxic challenge in heat shock-pretreated mice.
AB  - The inflammatory response induced by bacterial lipopolysaccharide (LPS) has
      profound metabolic and physiological effects. Thus hepatic glucose production is
      depressed after LPS administration, which is, at least in part, due to the
      downregulation of phosphoenolpyruvate carboxykinase (PEPCK) expression. PEPCK is
      a key regulatory enzyme of the gluconeogenic pathway. Expression of heat shock
      proteins (hsps) is a well-conserved response to stress correlated with protection
      from subsequent insults including inflammation. In this study, the expression of
      PEPCK was observed to be preserved after injection of LPS in heat shock
      pretreated mice. Protection of PEPCK expression was limited to the time after
      heat shock treatment that displayed hsp70. Comparison of the transcription rate
      and mRNA levels of PEPCK after LPS injection between mice that were heat shock
      pretreated or not indicated that the preservation of PEPCK expression was not due
      to initial protection from the LPS challenge. On the contrary, it was mediated by
      a rapid recovery after the LPS insult at the level of transcription. These
      observations suggest that the mechanism of heat shock-mediated protection (stress
      tolerance) after LPS challenge is due to an increase in the capacity of the
      organism to recover rather than deterrence from the insult.

PMID- 11959680
TI  - Feeding melatonin enhances the phase shifting response to triazolam in both young
      and old golden hamsters.
AB  - Aging alters many aspects of circadian rhythmicity, including responsivity to
      phase-shifting stimuli and the amplitude of the rhythm of melatonin secretion. As
      melatonin is both an output from and an input to the circadian clock, we
      hypothesized that the decreased melatonin levels exhibited by old hamsters may
      adversely impact the circadian system as a whole. We enhanced the diurnal rhythm
      of melatonin by feeding melatonin to young and old hamsters. Animals of both age
      groups on the melatonin diet showed larger phase shifts than control-fed animals
      in response to an injection with the benzodiazepine triazolam at a circadian time
      known to induce phase advances in the activity rhythm of young animals. Thus
      melatonin treatment can increase the sensitivity of the circadian timing system
      of young animals to a nonphotic stimulus, and the ability to increase this
      sensitivity persists into old age, indicating exogenous melatonin might be useful
      in reversing at least some age-related changes in circadian clock function.

PMID- 11959681
TI  - Predominant activation of endothelin-dependent cardiac hypertrophy by
      norepinephrine in rat left ventricle.
AB  - Locally released endothelin (ET)-1 has been recently identified as an important
      mediator of cardiac hypertrophy. It is still unclear, however, which primary
      stimulus specifically activates ET-dependent signaling pathways. We therefore
      examined in adult rats (n = 51) the effects of a selective ET(A) receptor
      antagonist in experimental models of cardiac hypertrophy, in which myocardial
      growth is predominantly initiated by a single primary stimulus. Rats were exposed
      to mechanical overload (ascending aortic stenosis), increased levels of
      circulating ANG II (ANG II infusion combined with hydralazine), or adrenergic
      stimulation (infusion of norepinephrine in a subpressor dose) for 7 days. All
      experimental treatments significantly increased left ventricular weight/body
      weight ratios compared with untreated rats, whereas systolic left ventricular
      peak pressure was increased only after ascending aortic stenosis. ET(A) receptor
      blockade exclusively reduced norepinephrine-induced cardiac hypertrophy and
      atrial natriuretic peptide gene expression. Blood pressure levels and heart rates
      remained unaffected during ET(A) receptor blockade in all experimental groups.
      These data indicate that in rat left ventricle, the ET-dependent signaling
      pathway leading to early development of cardiac hypertrophy and fetal gene
      expression is primarily activated by norepinephrine.

PMID- 11959682
TI  - Effects of amylin-related peptides on food intake, meal patterns, and gastric
      emptying in rats.
AB  - We previously demonstrated that amylin inhibits food intake and gastric emptying
      in rats with half-maximal effective doses (ED(50)s) of 8 and 3 pmol x kg(-1) x
      min(-1) and maximal inhibitions of 78 and 60%, respectively. In this study of
      identical design, rats received intravenous infusions of salmon calcitonin (sCT),
      rat calcitonin (rCT), rat calcitonin gene-related peptide (rCGRP), and rat
      adrenomedullin (rADM) for 3 h at dark onset, and food intake was measured for 17
      h or for 15 min and gastric emptying of saline was measured during the final 5
      min. sCT, rCGRP, and rADM inhibited food intake with estimated ED(50)s of 0.5,
      26, and 35 pmol x kg(-1) x min(-1) and maximal inhibitions of 88, 90, and 49%,
      respectively. rCT was not effective at doses up to 100 pmol x kg(-1) x min(-1).
      sCT, rCGRP, rADM, and rCT inhibited gastric emptying with ED(50)s of 1, 130, 160,
      and 730 pmol x kg(-1) x min(-1) and maximal inhibitions of 60, 66, 60, and 33%,
      respectively. These results suggest that amylin and sCT may act by a common
      mechanism to decrease food intake, which includes inhibition of gastric emptying.

PMID- 11959683
TI  - Seasonal dynamics of flight muscle fatty acid binding protein and catabolic
      enzymes in a migratory shorebird.
AB  - We developed an ELISA to measure heart-type fatty acid binding protein (H-FABP)
      in muscles of the western sandpiper (Calidris mauri), a long-distance migrant
      shorebird. H-FABP accounted for almost 11% of cytosolic protein in the heart.
      Pectoralis H-FABP levels were highest during migration (10%) and declined to 6%
      in tropically wintering female sandpipers. Premigratory birds increased body fat,
      but not pectoralis H-FABP, indicating that endurance flight training may be
      required to stimulate H-FABP expression. Juveniles making their first migration
      had lower pectoralis H-FABP than adults, further supporting a role for flight
      training. Aerobic capacity, measured by citrate synthase activity, and fatty acid
      oxidation capacity, measured by 3-hydroxyacyl-CoA-dehydrogenase and carnitine
      palmitoyl transferase activities, did not change during premigration but
      increased during migration by 6, 12, and 13%, respectively. The greater relative
      induction of H-FABP (+70%) with migration than of catabolic enzymes suggests that
      elevated H-FABP is related to the enhancement of uptake of fatty acids from the
      circulation. Citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and carnitine
      palmitoyl transferase were positively correlated within individuals, suggesting
      coexpression, but enzyme activities were unrelated to H-FABP levels.

PMID- 11959684
TI  - Neuropeptide Y effects on vasorelaxation and intestinal contraction in the
      Atlantic cod Gadus morhua.
AB  - Neuropeptide Y (NPY) has prominent cardiovascular effects in mammals and sharks,
      but no such effect has previously been demonstrated in any teleost fish. In the
      Atlantic cod, we found that cod NPY (10(-10)-10(-6) M) relaxed celiac arteries
      precontracted with epinephrine, and weak contractions were elicited in intestinal
      ring preparations. A few NPY-immunoreactive nerve fibers were present along small
      gut arteries. The results suggest that cod NPY produces vasorelaxation both by a
      direct action on smooth muscle and by release of prostaglandins, but with no
      involvement of nitric oxide, leukotrienes, or endothelium-derived relaxing
      factors. An additional indirect effect involving another neurotransmitter may
      occur. Cod NPY (10(-7) M) and human NPY (10(-7) M) had identical effects on the
      vessels. Small differences only in the effects of porcine [Leu(31),Pro(34)]NPY,
      NPY-(13-36), and cod NPY suggest the presence of a Y(1) subfamily receptor,
      similar to the zebrafish Ya receptor. A physiological role for NPY in teleost
      vasculature is concluded, but surprisingly the effect, a vasodilation, is
      opposite to that in mammals and is mediated by prostaglandins.

PMID- 11959685
TI  - Stressful animal housing conditions and their potential effect on sympathetic
      neurotransmission in mice.
AB  - Although the sympathetic nervous system (SNS) plays a major role in mediating the
      peripheral stress response, due consideration is not usually given to the effects
      of prolonged stress on the SNS. The present study examined changes in
      neurotransmission in the SNS after exposure of mice (BALB/c) to stressful housing
      conditions. Focal extracellular recording of excitatory junction currents (EJCs)
      was used as a relative measure of neurotransmitter release from different regions
      of large surface areas of the mouse vas deferens. Mice were either group housed
      (control), isolation housed (social deprivation), group housed in a room
      containing rats (rat odor stress), or isolation housed in a room containing rats
      (concurrent stress). Social deprivation and concurrent stressors induced an
      increase of 30 and 335% in EJC amplitude, respectively. The success rate of
      recording EJCs from sets of varicosities in the concurrent stressor group was
      greater compared with all other groups. The present study has shown that some
      common animal housing conditions act as stressors and induce significant changes
      in sympathetic neurotransmission.

PMID- 11959686
TI  - Anti-inflammatory agents inhibit the induction of leptin by tumor necrosis factor
      alpha.
AB  - Tumor necrosis factor (TNF)-alpha stimulates the secretion of the adipocyte
      derived hormone leptin. However, the cellular mechanisms by which TNF-alpha
      influences leptin production are poorly understood. To examine this issue,
      epididymal fat pads were isolated from mice and cultured in recombinant murine
      TNF-alpha (100 ng/ml). Compared with medium-treated controls, steady-state leptin
      expression was increased in TNF-alpha-treated explants. Culture with inhibitors
      of translation (cycloheximide) or transcription (actinomycin-D) abrogated the
      induction of leptin following TNF-alpha. Explants were also cultured in the
      presence of the anti-inflammatory p38 mitogen-activated protein kinase inhibitor
      (SB-203580) or PG J(2) metabolite [15-deoxy-Delta(12,14)-PG J(2) (PGJ)] and then
      exposed to TNF-alpha. Both compounds completely abolished TNF-alpha-induced
      increases in leptin production. To test the relevance of this in vivo, mice were
      pretreated with PGJ and then given TNF-alpha. PGJ treatment markedly blunted the
      TNF-alpha-induced increase in leptin, TNF-alpha, and interleukin-6 gene
      expression in epididymal adipose tissue. Collectively, these data indicate that
      TNF-alpha acutely activates leptin expression and that anti-inflammatory agents
      can abrogate TNF-alpha-induced hyperleptinemia.

PMID- 11959687
TI  - Facilitatory role of NO in neural norepinephrine release in the rat kidney.
AB  - We examined modulation by nitric oxide (NO) of sympathetic neurotransmitter
      release and vasoconstriction in the isolated pump-perfused rat kidney. Electrical
      renal nerve stimulation (RNS; 1 and 2 Hz) increased renal perfusion pressure and
      renal norepinephrine (NE) efflux. Nonselective NO synthase (NOS) inhibitors
      [N(omega)-nitro-L-arginine methyl ester (L-NAME) or N(omega)-nitro-L-arginine],
      but not a selective neuronal NO synthase inhibitor (7-nitroindazole sodium salt),
      suppressed the NE efflux response and enhanced the perfusion pressure response.
      Pretreatment with L-arginine prevented the effects of L-NAME on the RNS-induced
      responses. 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
      (carboxy-PTIO), which eliminates NO by oxidizing it to NO(2), suppressed the NE
      efflux response, whereas the perfusion pressure response was less susceptible to
      carboxy-PTIO. 8-Bromoguanosine cGMP suppressed and a guanylate cyclase inhibitor
      [4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one] enhanced the RNS
      induced perfusion pressure response, but neither of these drugs affected the NE
      efflux response. These results suggest that endogenous NO facilitates the NE
      release through cGMP-independent mechanisms, NO metabolites formed after NO(2)
      rather than NO itself counteract the vasoconstriction, and neuronal NOS does not
      contribute to these modulatory mechanisms in the sympathetic nervous system of
      the rat kidney.

PMID- 11959688
TI  - M(3)-receptor knockout mice: muscarinic receptor function in atria, stomach
      fundus, urinary bladder, and trachea.
AB  - Negative chronotropic and smooth muscle contractile responses to the nonselective
      muscarinic agonist carbamylcholine were compared in isolated tissues from M(3)
      muscarinic receptor knockout and wild-type mice. Carbamylcholine (10(-8)-3.0 x
      10(-5) M) induced a concentration-dependent decrease in atrial rate that was
      similar in atria from M(3)-receptor knockout and wild-type mice, indicating that
      M(3) receptors were not involved in muscarinic receptor-mediated atrial rate
      decreases. In contrast, the M(3) receptor was a major muscarinic receptor
      involved in smooth muscle contraction of stomach fundus, urinary bladder, and
      trachea, although differences existed in the extent of M(3)-receptor involvement
      among the tissues. Contraction to carbamylcholine was virtually abolished in
      urinary bladder from M(3)-receptor knockout mice, suggesting that contraction was
      predominantly due to M(3)-receptor activation. However, approximately 50-60%
      maximal contraction to carbamylcholine occurred in stomach fundus and trachea
      from M(3)-receptor knockout mice, indicating that contraction in these tissues
      was also due to M(2)-receptor activation. High concentrations of carbamylcholine
      relaxed the stomach fundus from M(3)-receptor knockout mice by M(1)-receptor
      activation. Thus M(3)-receptor knockout mice provided unambiguous evidence that
      M(3) receptors 1) play no role in carbamylcholine-induced atrial rate reduction,
      2) are the predominant receptor mediating carbamylcholine-induced urinary bladder
      contractility, and 3) share contractile responsibility with M(2) receptors in
      mouse stomach fundus and trachea.

PMID- 11959689
TI  - Involvement of adrenergic pathways in activation of catalase by myocardial
      ischemia-reperfusion.
AB  - In situ rabbit hearts were subjected to 15 min of regional myocardial ischemia,
      and at various time points of reperfusion, antioxidant enzyme activity and mRNA
      expression were measured in ischemic and nonischemic myocardium. Catalase
      activity increased significantly in both ischemic and nonischemic myocardium,
      peaking at 1 h after reperfusion and then gradually returning to the control
      level. Northern blot analysis showed enhanced expression of catalase mRNA in both
      areas. There were no changes in redox status, because glutathione levels were not
      altered by ischemia-reperfusion (I/R). We also tested whether catalase activation
      in the heart results from signaling pathways that might influence not only the
      heart but also other organs. We found that catalase activity in the brain was
      increased after myocardial I/R and ischemic stress to the intestine was
      equipotent to myocardial I/R in catalase activation. We next sought to elucidate
      the possible involvement of the adrenergic system in catalase stimulation induced
      by ischemic stimuli. After pretreatment with the alpha-adrenergic receptor
      antagonist prazosin, I/R failed to increase catalase activity in the heart and
      brain. Intravenous norepinephrine increased catalase activity in the heart,
      brain, and liver. This study shows that brief I/R activates a signaling mechanism
      to induce catalase activation in multiple organs and the alpha-adrenergic system
      is involved as an intermediate pathway in this signal transmission.

PMID- 11959690
TI  - Cardiovascular responses to caloric restriction and thermoneutrality in C57BL/6J
      mice.
AB  - We utilized variations in caloric availability and ambient temperature (T(a)) to
      examine interrelationships between energy expenditure and cardiovascular function
      in mice. Male C57BL/6J mice (n = 6) were implanted with telemetry devices and
      housed in metabolic chambers for measurement of mean arterial pressure (MAP),
      heart rate (HR), O(2) consumption (VO(2)), and locomotor activity. Fasting (T(a)
      = 23 degrees C), initiated at the onset of the dark phase, resulted in large and
      transient depressions in MAP, HR, VO(2), and locomotor activity that occurred
      during hours 6-17, which suggests torporlike episodes. Food restriction (14 days,
      60% of baseline intake) at T(a) = 23 degrees C resulted in progressive reductions
      in MAP and HR across days that were coupled with an increasing occurrence of
      episodic torporlike reductions in HR (<300 beats/min) and VO(2) (<1.0 ml/min).
      Exposure to thermoneutrality (T(a) = 30 degrees C, n = 6) reduced baseline light
      period MAP (-14 +/- 2 mmHg) and HR (-184 +/- 12 beats/min). Caloric restriction
      at thermoneutrality produced further reductions in MAP and HR, but indications of
      torporlike episodes were absent. The results reveal that mice exhibit robust
      cardiovascular responses to both acute and chronic negative energy balance.
      Furthermore, we conclude that T(a) is a very important consideration when
      assessing cardiovascular function in mice.

PMID- 11959691
TI  - Frequency modulation of mesenteric and renal vascular resistance.
AB  - The hypothesis was tested that low-frequency vasomotions in individual vascular
      beds are integrated by the cardiovascular system, such that new fluctuations at
      additional frequencies occur in arterial blood pressure. In anesthetized rats (n
      = 8), the sympathetic splanchnic and renal nerves were simultaneously stimulated
      at combinations of frequencies ranging from 0.075 to 0.8 Hz. Blood pressure was
      recorded together with mesenteric and renal blood flow velocities. Dual nerve
      stimulation at low frequencies (<0.6 Hz) caused corresponding oscillations in
      vascular resistance and blood pressure, whereas higher stimulation frequencies
      increased the mean levels. Blood pressure oscillations were only detected at the
      individual stimulation frequencies and their harmonics. The strongest periodic
      responses in vascular resistance were found at 0.40 +/- 0.02 Hz in the mesenteric
      and at 0.32 +/- 0.03 Hz (P < 0.05) in the renal vascular bed. Thus frequency
      modulation of low-frequency vasomotions in individual vascular beds does not
      cause significant blood pressure oscillations at additional frequencies.
      Furthermore, our data suggest that sympathetic modulation of mesenteric vascular
      resistance can initiate blood pressure oscillations at slightly higher
      frequencies than sympathetic modulation of renal vascular resistance.

PMID- 11959692
TI  - Protein kinase-dependent and Ca(2+)-independent cAMP inhibition of ANP release in
      beating rabbit atria.
AB  - Regulation of atrial release of atrial natriuretic peptide (ANP) is coupled to
      changes in atrial dynamics. However, the mechanism by which mechanical stretch
      controls myocytic ANP release must be defined. The purpose of this study was to
      define the mechanism by which cAMP controls myocytic ANP release in perfused,
      beating rabbit atria. The cAMP-elevating agents forskolin and 3-isobutyl-1
      methylxanthine (IBMX) inhibited myocytic ANP release. The activation of adenylyl
      cyclase with forskolin inhibited ANP release, which was a function of an increase
      in cAMP production. Inhibitors for L-type Ca(2+) channels and protein kinase A
      (PKA) attenuated a minor portion of the forskolin-induced inhibition of ANP
      release. Go-6976 and KN-62, which are specific inhibitors for protein kinase C
      alpha and Ca(2+)/calmodulin kinase, respectively, failed to modulate forskolin
      induced inhibition of ANP release. The nonspecific protein kinase inhibitor
      staurosporine blocked forskolin-induced inhibition of ANP release in a dose
      dependent manner. Staurosporine but not nifedipine shifted the relationship
      between cAMP and ANP release. Inhibitors for L-type Ca(2+) channels and PKA and
      staurosporine blocked forskolin-induced accentuation of atrial dynamics. These
      results suggest that cAMP inhibits atrial myocytic release of ANP via protein
      kinase-dependent and L-type Ca(2+)-channel-dependent and -independent signaling
      pathways.

PMID- 11959693
TI  - Molecular and functional characterization of a urea transporter from the kidney
      of a short-finned pilot whale.
AB  - Cetaceans (whales and dolphins) always excrete urine with an osmolality markedly
      higher than that of plasma. Although the mechanisms by which cetaceans
      concentrate urine have not been elucidated, data support a role for medullary
      urea accumulation in this process, as is the case for terrestrial mammals.
      Therefore, we hypothesized that facilitated urea transporters are present in the
      kidney of cetaceans. Using 5'/3'-rapid amplification of cDNA ends, we cloned a
      2.7-kb cDNA from the kidney of the short-finned pilot whale Globicephala
      macrorhynchus. The putative open-reading frame encoded a 397-amino acid protein
      [pilot whale urea transporter A2 (whUT-A2)] that has 94% amino acid sequence
      identity to the A2 isoform of the human urea transporter (hUT-A2). Heterologous
      expression of whUT-A2 cRNA in Xenopus oocytes induced phloretin-inhibitable urea
      transport. Although Northern analysis and RT-PCR indicated that whUT-A2 was
      exclusively expressed in kidney, Western blotting using a polyclonal antibody to
      rat UT-A1/UT-A2 detected various immunoreactive proteins in kidney and other
      tissues. Furthermore, RT-PCR analysis suggested the presence of alternatively
      spliced UT-A transcripts in the kidney as well as extrarenal tissues. We conclude
      that renal urea transporters are highly conserved among mammals inhabiting
      terrestrial and pelagic environments. A urea-based concentrating mechanism,
      presumably evolved to meet the demands of an arid terrestrial environment, may
      have contributed a fortuitous preadaptation that enabled the ancestors of
      cetaceans to reinvade the sea.

PMID- 11959694
TI  - Behavioral, plasma, and calorimetric changes related to food texture modification
      in men.
AB  - We hypothesized that food texture modifications might alter anticipatory
      reflexes, feeding behavior, and the postabsorptive consequences of ingestion. Two
      sets of complete meals with different textures but the same macronutrient
      composition were prepared. The first set was either a soup containing chunks of
      food (mixture) or the same soup blended until smooth (puree). The second set was
      either a rusk (R), a sandwich loaf (SL), or a liquid rusk meal (LR). We measured
      hunger and fullness feelings after ingestion of each food in a calibrated lunch,
      the ingestion rate, the duration between lunch and a spontaneous dinner request,
      the energy value, and the macronutrient composition of the ad libitum dinner. We
      also studied plasma modifications and respiratory gas exchanges from lunch to
      dinner. Feelings of hunger and fullness were not affected by texture
      modifications. The puree soup was consumed faster than the mixture (P < 0.05),
      and insulin, triacylglycerol, and energy expenditure were greater with the puree
      (P < 0.05). LR was less palatable than the other rusk lunch versions (P < 0.001),
      and R was ingested more slowly (P < 0.05). The lowest increase in plasma glucose
      occurred with SL, and the highest energy expenditure was seen with LR (P < 0.05).
      In humans, food texture modification affects not only eating patterns and
      palatability of ingestants but also metabolic management.

PMID- 11959695
TI  - Glomerular and tubular responses to N(G)-nitro-L-arginine methyl ester are age
      dependent in conscious lambs.
AB  - The present experiments were carried out to investigate the role of endogenously
      produced NO in modulating renal function during postnatal maturation under
      physiological conditions. In conscious, chronically instrumented lambs aged
      approximately 1 (n = 8) and approximately 6 wk (n = 8) of postnatal life, various
      parameters of glomerular and tubular function were measured for 1 h before and 1
      h after intravenous injection of 20 mg/kg of N(G)-nitro-L-arginine methyl ester
      (L-NAME; experiment 1) or its inactive isomer D-NAME (experiment 2). After
      administration of L-NAME to 1-wk-old lambs, glomerular filtration rate (GFR) and
      filtration factor (FF) decreased by approximately 50% at 20 min, remaining
      decreased at 60 min. In 6-wk-old lambs, GFR and FF remained constant after L
      NAME. Proximal fractional Na(+) reabsorption decreased after L-NAME
      administration to lambs aged 6 wk, resulting in a prompt natriuresis; this was
      sustained for 60 min. There were no effects of L-NAME on proximal fractional
      Na(+) reabsorption in 1-wk-old lambs. In 6-wk-old lambs, urinary flow rate
      increased by approximately 500%, free water clearance increased by approximately
      50%, and urinary osmolality decreased by approximately 60% after L-NAME
      administration; no effects on these variables were measured in 1-wk-old lambs.
      The diuresis after L-NAME administration to 6-wk-old lambs was unaccompanied by
      any changes in plasma levels of arginine vasopressin. There were no effects of D
      NAME on any of the measured variables. We conclude that endogenously produced
      nitric oxide modulates glomerular and tubular function in an age-dependent
      manner.

PMID- 11959696
TI  - Neuronal NO modulates spontaneous and ANG II-stimulated fetal swallowing behavior
      in the near-term ovine fetus.
AB  - Spontaneous fetal swallowing occurs at a markedly higher rate compared with
      spontaneous adult drinking activity. This high rate of fetal swallowing is
      critical for amniotic fluid volume regulation. Central NO is critical for
      maintaining the normal rate of fetal swallowing, as nonselective inhibition of NO
      (with central N(G)-nitro-L-arginine methyl ester) suppresses spontaneous and
      angiotensin II (ANG II)-stimulated swallowing. We sought to differentiate the
      contributions of central endothelial vs. neuronal NO in the regulation of
      spontaneous and stimulated fetal swallowing, using a selective neuronal NO
      synthase (nNOS) inhibitor. Six time-dated pregnant ewes and fetuses were
      chronically prepared with fetal vascular and intracerebroventricular (i.c.v.)
      catheters and electrocorticogram (ECoG) and esophageal electromyogram electrodes
      and studied at 130 +/- 1 days of gestation. After an initial 2-h baseline period
      (0-2 h), the selective nNOS inhibitor N-propyl-L-arginine (NPLA) was injected
      i.c.v. (2-4 h). At 4 h, the dose of NPLA was repeated, together with ANG II, and
      fetal swallowing was monitored for a final 2 h. Four fetuses also received an
      identical control study (on an alternate day) in which NPLA was replaced with
      artificial cerebrospinal fluid (aCSF). Suppression of nNOS by i.c.v. NPLA
      significantly reduced mean (+/- SE) spontaneous fetal swallowing (1.35 +/- 0.12
      to 0.50 +/- 0.07 swallows/min; P < 0.001). Injection of ANG II in the presence of
      NPLA had no dipsogenic effect on fetal swallowing (0.68 +/- 0.09 swallows/min).
      In the aCSF study, i.c.v. aCSF did not change fetal swallowing (0.93 +/- 0.10 vs.
      0.95 +/- 0.09 swallows/min), whereas i.c.v. ANG II resulted in a significant
      increase in the rate of fetal swallowing (2.0 +/- 0.04 swallows/min; P = 0.001).
      We speculate that the suppressive dipsogenic effects of central NPLA indicate
      that spontaneous and ANG II- stimulated fetal swallowing is dependent on central
      nNOS activity.

PMID- 11959697
TI  - Aortic blood flow subtraction: an alternative method for measuring total renal
      blood flow in conscious dogs.
AB  - We have measured total renal blood flow (TRBF) as the difference between signals
      from ultrasound flow probes implanted around the aorta above and below the renal
      arteries. The repeatability of the method was investigated by repeated,
      continuous infusions of angiotensin II and endothelin-1 seven times over 8 wk in
      the same dog. Angiotensin II decreased TRBF (350 +/- 16 to 299 +/- 15 ml/min), an
      effect completely blocked by candesartan (TRBF 377 +/- 17 ml/min). Subsequent
      endothelin-1 infusion reduced TRBF to 268 +/- 20 ml/min. Bilateral carotid
      occlusion (8 sessions in 3 dogs) increased arterial blood pressure by 49% and
      decreased TRBF by 12%, providing an increase in renal vascular resistance of 69%.
      Dynamic analysis showed autoregulation of renal blood flow in the frequency range
      <0.06-0.07 Hz, with a peak in the transfer function at 0.03 Hz. It is concluded
      that continuous measurement of TRBF by aortic blood flow subtraction is a
      practical and reliable method that allows direct comparison of excretory function
      and renal blood flow from two kidneys. The method also allows direct comparison
      between TRBF and flow in the caudal aorta.

PMID- 11959698
TI  - Obesity by choice: the powerful influence of nutrient availability on nutrient
      intake.
AB  - The consumption of nutrients by rodents is markedly influenced by the number of
      containers of each nutrient provided. Most rats given a choice from separate
      sources of protein, carbohydrate, and fat thrived if given one cup of each but
      half failed to thrive if given one cup of each and three extra cups of
      carbohydrate or fat. Rats given five bottles of sucrose solution and one bottle
      of water became fatter than rats given five bottles of water and one of sucrose.
      These studies in rats may point to a model for human obesity, in which the
      availability of food can override physiological controls of ingestion.

PMID- 11959700
TI  - CT screening for lung cancer: frequency and significance of part-solid and
      nonsolid nodules.
AB  - OBJECTIVE: In the Early Lung Cancer Action Project (ELCAP), we found not only
      solid but also part-solid and nonsolid nodules in patients at both baseline and
      repeat CT screening for lung cancer. We report the frequency and significance of
      part-solid and nonsolid nodules in comparison with solid nodules. MATERIALS AND
      METHODS: We reviewed all instances of a positive finding in patients at baseline
      (from one to six noncalcified nodules) and annual repeat screenings (from one to
      six newly detected noncalcified nodules with interim growth) to classify each of
      the nodules as solid, part-solid, or nonsolid. We defined a solid nodule as a
      nodule that completely obscures the entire lung parenchyma within it. Part-solid
      nodules are those having sections that are solid in this sense, and nonsolid
      nodules are those with no solid parts. Chi-square statistics were used to test
      for differences in the malignancy rates. RESULTS: Among the 233 instances of
      positive results at baseline screening, 44 (19%) involved a part-solid or
      nonsolid largest nodule (16 part-solid and 28 nonsolid). Among these 44 cases of
      positive findings, malignancy was diagnosed in 15 (34%) as opposed to a 7%
      malignancy rate for solid nodules (p = 0.000001). The malignancy rate for part
      solid nodules was 63% (10/16), and the rate for nonsolid nodules was 18% (5/28).
      Even after standardizing for nodule size, the malignancy rate was significantly
      higher for part-solid nodules than for either solid ones (p = 0.004) or nonsolid
      ones (p = 0.03). The malignancy type in the part-solid or nonsolid nodules was
      predominantly bronchioloalveolar carcinoma or adenocarcinoma with
      bronchioloalveolar features, contrasting with other subtypes of adenocarcinoma
      found in the solid nodules (p = 0.0001). At annual repeat screenings, only 30
      instances of positive test results have been obtained; seven of these involved
      part-solid or nonsolid nodules. CONCLUSION: In CT screening for lung cancer, the
      detected nodule commonly is either only part-solid or nonsolid, but such a nodule
      is more likely to be malignant than a solid one, even when nodule size is taken
      into account.

PMID- 11959701
TI  - Decreasing the radiation dose for renal stone CT: a feasibility study of single-
      and multidetector CT.

PMID- 11959702
TI  - Dynamic CT features of inhalational anthrax infection.

PMID- 11959703
TI  - Determinants of differences among radiologists in starting salaries.
AB  - OBJECTIVE: We sought to ascertain the actual effect of each of a broad range of
      factors that plausibly might affect starting salary. MATERIALS AND METHODS: We
      surveyed radiologists who completed training in 1997 and obtained 487 relevant
      responses. Multiple regression analysis was used to identify the independent
      effects of characteristics of the physician, his or her job and employment
      search, and market area characteristics of his or her practice locality. RESULTS:
      Academic starting salaries were, other things equal, 6% below private practice.
      Residency-only graduates had incomes 7% below a typical fellowship income. Only a
      few fellowship fields garnered incomes that were significantly different from the
      typical income. More managed care in a locality was associated with lower income,
      and a higher percentage of elderly in the locality was associated with a higher
      income. We found no statistically significant (p < 0.05) effects of sex, job
      location constraints, local per capita income, local cost of living, or
      (generally) graduate quality as measured by the ranking of a graduate's residency
      program. CONCLUSION: The determinants of income are multiple and varied,
      including physician characteristics, such as field of subspecialty training; job
      characteristics, such as academic versus private practice employment; and market
      area characteristics. However, the study yielded as many puzzling, negative
      findings, such as the lack of effect of physician quality or of even severe
      locational constraints, as positive, expected findings.

PMID- 11959704
TI  - Too few radiologists?
AB  - OBJECTIVE: The purpose of our study was to model the supply and demand for
      diagnostic radiologists over the next 30 years under alternative scenarios.
      MATERIALS AND METHODS: We used responses from the American College of Radiology's
      2000 Survey of Diagnostic Radiologists and Radiation Oncologists to determine the
      current age distribution and activity of diagnostic radiologists. The numbers
      entering the profession were projected using three assumptions: no change in
      training programs, reduction of residency to 3 years (or otherwise increasing the
      annual number of graduates by one third), and elimination of most fellowship
      programs. Demand projections assume a 5% shortage in 2001 and depend on growth
      rates of the population, aging, scenarios of growth of age-standardized demand,
      and the effect of possibly productivity-enhancing technologies such as PACS
      (picture archiving and communication systems). RESULTS: Only a one-third increase
      in annual graduates materially increases the work-force relative to current
      training patterns. In all cases, the growth rate of the demand for radiologists
      far outstrips the supply over a 30-year horizon. In the shorter term, projections
      of current trends point to an increasing shortage, but rapid major productivity
      increases could produce a surplus. CONCLUSION: Those in the field of diagnostic
      radiology should consider measures to mitigate the increasing shortage, while
      monitoring developments that might signal departures from current trends in
      supply and demand.

PMID- 11959705
TI  - Complications of lung abscess aspiration and drainage.

PMID- 11959706
TI  - Coil sensitivity encoding in MR imaging: advantages and disadvantages in clinical
      practice.

PMID- 11959707
TI  - Spontaneous discharge of a firearm in an MR imaging environment.

PMID- 11959708
TI  - Dependent pooling: a contrast-enhanced sign of cardiac arrest during CT.
AB  - OBJECTIVE: The purpose of this study is to describe the imaging features of
      cardiac arrest that occur during CT. CONCLUSION: CT features of cardiac arrest
      are characterized by a pooling of contrast agent in the dependent parts of the
      right side of the body, including the venous system and the right lobe of the
      liver. If medical professionals are aware of these specific imaging features,
      prompt cardiac resuscitation can be initiated to avoid permanent brain damage and
      death.

PMID- 11959710
TI  - Etymology of selected medical terms used in radiology: the mythologic connection.

PMID- 11959711
TI  - Quality of virtual colonoscopy in patients who have undergone radiation therapy
      or surgery: how successful are we?
AB  - OBJECTIVE: In patients who have a history of abdominopelvic radiation, surgery,
      or both, conventional colonoscopy may fail to examine the entire colon. The
      purpose of this study is to assess whether high-quality virtual colonoscopy can
      be achieved in this patient population. MATERIALS AND METHODS: After colonic
      cleansing, 61 patients (16 men and 45 women; mean age, 64 years; age range, 27-81
      years) underwent 63 virtual colonoscopy examinations after using either single-
      or multidetector CT (slice thickness, 3.75-5.0 mm; table speed, 1.7-11.25 cm/sec;
      pitch, 1.5-3.0; and overlapped reconstructions, 1.95-2.5 cm) in supine and prone
      positions after IV administration of 1 mg of glucagon and rectal air
      insufflation. Conventional two-dimensional axial images were analyzed on a PACS
      (picture archiving and communication system) workstation. Two radiologists, who
      were unaware of patient history, independently evaluated the colonic distention
      on a 4-point scale (4 = optimal distention) and fluid retention on a 3-point
      scale (3 = no fluid) for all segments of the colon in patients who were imaged in
      both the supine and prone positions. Segmental and total average colon scores
      were calculated. RESULTS: Forty-one patients (65%; 43 examinations, 67%)
      underwent prior surgery, radiation, or both (surgery, n = 29; radiation, n = 3;
      both, n = 11). The average overall colonic distention and fluid retention for
      this group was 3.13 and 2.38, respectively, versus 3.24 and 2.3 in the control
      group (p = not significant). CONCLUSION: High-quality examinations were achieved
      in patients who had previously undergone radiation, surgery, or both with no
      clinically significant difference in distention or fluid retention compared with
      the controls.

PMID- 11959712
TI  - Gastric mucosa-associated lymphoid tissue lymphoma: helical CT findings and
      pathologic correlation.
AB  - OBJECTIVE: The purpose of this study was to describe helical CT findings of
      gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to correlate them
      with pathologic findings. MATERIALS AND METHODS: We retrospectively reviewed CT
      examinations of 58 patients with confirmed gastric MALT lymphomas. Using the
      histopathologic grade of the MALT lymphomas, we divided the patients into two
      groups: those with high-grade lymphoma (n = 21) and those with low-grade lymphoma
      (n = 37). Common CT findings for the two groups were reviewed and compared.
      RESULTS: Forty (69%) of the 58 patients showed at least one abnormality of the
      stomach on CT. Abnormalities included diffuse or segmental gastric wall
      thickening (66%, 38/58), lymphadenopathy (40%, 23/58), ulcer (22%, 13/58), and
      gastric mass (3%, 2/58). Eighteen (31%) of 58 patients were found to have no
      abnormality. The high-grade group had a higher incidence of abnormalities seen on
      CT than the low-grade group (100% vs 51%, respectively). Gastric wall thickening
      in the high-grade group was more diffuse (48% vs 8%) and severe (71% vs 14%;
      severe or moderate) than that seen in the low-grade group. Lymphadenopathy was
      visualized in 67% of the high-grade group and in 24% of the low-grade group.
      Gastric ulcer was found in 57% of the high-grade group and in only 5% of the low
      grade group. The gastric mass formation was seen in only two patients in the high
      grade group. CONCLUSION: The CT findings of gastric MALT lymphoma that the two
      groups had in common were gastric wall thickening and lymphadenopathy. Although
      our results pointed to no specific CT finding for differentiating high-grade from
      low-grade gastric MALT lymphomas, we found that the absence of abnormality on CT
      is highly predictive of low-grade MALT lymphoma.

PMID- 11959713
TI  - Non-Hodgkin's lymphoma of the appendix: clinical and CT findings with pathologic
      correlation.
AB  - OBJECTIVE: The purpose of this report is to describe the clinical, CT, and
      pathologic features of non-Hodgkin's lymphoma of the vermiform appendix.
      CONCLUSION: Non-Hodgkin's lymphoma of the appendix typically manifests with acute
      symptoms in patients who have no prior history of lymphoma. Most patients with
      the disease present clinically with signs and symptoms suggestive of acute
      appendicitis. On CT, lymphomatous infiltration of the appendix produces markedly
      diffuse mural soft-tissue thickening (range of diameters, 2.5-4.0 cm; mean
      diameter, 3.2 cm). The vermiform morphology of the appendix is usually
      maintained, and aneurysmal dilatation of the lumen is sometimes seen. Stranding
      of the periappendiceal fat seen on CT may represent superimposed inflammation or
      even direct lymphomatous extension. Coexisting abdominal lymphadenopathy is not
      seen in all patients. Although appendiceal lymphoma is rare, the characteristic
      CT appearance could lead to a preoperative diagnosis.

PMID- 11959715
TI  - Renal excretion of ingested gastrografin: clinical relevance in early
      postoperative treatment of patients who have undergone gastric surgery.
AB  - OBJECTIVE: We performed this study to evaluate the clinical relevance of renal
      excretion of ingested Gastrografin (methylglucamine diatrizoate) revealed on CT
      in the early treatment of patients who have undergone gastric surgery. SUBJECTS
      AND METHODS: Unenhanced abdominal CT was performed before and then 1 hr to 1 hr
      30 min after Gastrografin ingestion in 30 patients 7 days after gastric surgery
      and in 19 healthy adults who served as the control group. CT scans were reviewed
      for the opacification of the renal collecting system or urinary bladder after
      Gastrografin ingestion, a finding that represents renal excretion of the ingested
      contrast medium. RESULTS: In the control group, four (21 %) of the 19 healthy
      adults showed renal excretion of ingested Gastrografin visualized as
      opacification of the urinary tract on CT scans obtained 1 hr to 1 hr 30 min after
      ingestion of the substance. Renal excretion of the ingested Gastrografin was seen
      in 19 (63%) of the 30 patients, a significantly larger percentage than in the
      control group (z score, p < 0.01). No patient showed either radiologic or
      clinical evidence of leakage from the anastomotic site. CONCLUSION: Renal
      excretion of ingested Gastrografin is frequently visualized on CT in patients
      without anastomotic leakage during the early postoperative period after gastric
      surgery, and this phenomenon is not rare, even in healthy adults. Therefore,
      renal excretion seen on CT should not be regarded as a sign of anastomotic
      leakage in early postoperative patients.

PMID- 11959716
TI  - Dynamic sonography of pancreatic tumors: comparison with dynamic CT.
AB  - OBJECTIVE: The aim of this study was to examine the usefulness of dynamic
      sonography in the characterization of pancreatic tumors. MATERIALS AND METHODS:
      IV contrast-enhanced pancreatic sonography (dynamic sonography) with Levovist was
      performed in 43 patients with pancreatic mass lesions (32 with pancreatic
      adenocarcinomas, four with inflammatory pancreatic masses, three with islet cell
      tumors, two with serous cystadenomas, one with a solid and cystic tumor, and one
      with metastatic pancreatic cancer). We calculated a contrast index using a time
      intensity curve: contrast index equals elevation of intensity in the tumor
      divided by elevation of intensity in the pancreatic parenchyma. We classified the
      tumors into three groups according to the contrast index: a slightly enhanced
      group (contrast index < 0.5), a moderately enhanced group (contrast index = 0.5
      1.5), and a well-enhanced group (contrast index > 1.5), and we compared these
      results with those from dynamic CT. RESULTS: The contrast indexes of 32
      adenocarcinomas, four inflammatory pancreatic masses, three islet cell tumors,
      two serous cystadenomas, one solid and cystic tumor, and one metastatic tumor
      were, respectively, 0.12 +/- 0.095 (mean +/- SD), 0.54 +/- 0.420, 1.74 +/- 0.555,
      1.09 +/- 1.380, 1.67, and 2.07. Thirty-five tumors, including all 32
      adenocarcinomas, were classified in the slightly enhanced group, three were
      classified in the moderately enhanced group, and five were classified in the well
      enhanced group. In 93% (40/43) of tumors, the grade of enhancement on dynamic
      sonography was closely correlated with the grade of enhancement on dynamic CT.
      CONCLUSION: Dynamic sonography can assist in the characterization of pancreatic
      tumors.

PMID- 11959718
TI  - Bowel obstruction revealed by multidetector CT.

PMID- 11959719
TI  - Methylcellulose as a rectal contrast agent for MR imaging of rectal carcinoma.

PMID- 11959720
TI  - Sonographically observed echogenic response during intraoperative radiofrequency
      ablation of cirrhotic livers: pathologic correlation.
AB  - OBJECTIVE: We performed a study to determine the correlation between the diameter
      of the echogenic response observed with intraoperative sonography during
      radiofrequency ablation of the cirrhotic liver and the mean diameter of tissue
      necrosis. SUBJECTS AND METHODS: A total of 22 intraoperative radiofrequency
      ablations were created in 11 cirrhotic livers. The largest diameter of the
      sonographically observed echogenic response surrounding and perpendicular to the
      radiofrequency probe was measured. The subsequent zone of necrosis observed at
      pathology in the hepatectomy specimens after liver transplantation was measured
      in three planes and compared with the measured diameter of the echogenic
      response. RESULTS: During all except three ablations, a hyperechoic region was
      visualized surrounding the radiofrequency probe. The diameter of the echogenic
      response correlated significantly with the mean diameter of necrosis (correlation
      coefficient, 0.84). However, the echogenic response overestimated the minimal
      diameter of necrosis (mean difference, 0.8 +/- 0.4 cm) in 18 of 22 ablations and
      underestimated the maximum diameter of necrosis (mean difference, 0.9 +/- 0.8 cm)
      in 16 of 22 ablations. CONCLUSION: The diameter of the echogenic response
      observed with intraoperative sonography during radiofrequency ablation of the
      cirrhotic liver correlates closely with the mean diameter of the subsequent area
      of tissue necrosis. However, the solitary diameter of the echogenic response as
      measured in our study was often greater than the smallest diameter and less than
      the largest diameter of the area of tissue necrosis. Therefore, the echogenic
      response associated with radiofrequency ablation of the cirrhotic liver should be
      viewed only as a rough approximation of the area of induced tissue necrosis; the
      final assessment of the adequacy of ablation should be deferred to an alternative
      imaging technique.

PMID- 11959721
TI  - Transient postpartum portosystemic shunting revealed by MR venography.

PMID- 11959722
TI  - Thin-section multidetector CT angiography of renal artery stents.
AB  - OBJECTIVE: This study was undertaken as a pilot investigation to compare
      multidetector CT angiography with conventional catheter angiography for the
      visualization of the renal artery lumen after renal artery stent placement.
      SUBJECTS AND METHODS: CT angiography was performed within 24-48 hr of renal
      artery stent placement in 15 patients. Two patients had bilateral stents,
      resulting in a total of 17 stents. CT angiography was performed using a
      multidetector scanner and a bolus of IV contrast material with the scanning delay
      determined by a small-volume timing bolus. A volumetric data set was acquired
      through the stented arteries in the axial plane using a 4.0 x 1.25 mm detector
      configuration and a pitch of 3:1. The stent lumen diameter, as measured on direct
      CT angiography and curved multiplanar reformations in both the axial and coronal
      planes, was compared with that measured on catheter angiography. RESULTS: The
      lumina of all 17 stents were well visualized and patent on both CT angiography
      and catheter angiography. Anatomic definition, including stent position and wall
      apposition in the renal artery, correlated well with catheter angiography. The
      diameter of the renal artery stent lumen measured on catheter angiography (mean,
      5.9 +/- 1.3 mm) was greater than that on CT angiography (mean stent lumen
      diameter for direct axial plane was 4.6 +/- 1.0 mm, for curved multiplanar
      reformations in the axial plane was 4.3 +/- 1.0 mm, and for curved multiplanar
      reformations in the coronal plane was 4.4 +/- 1.0 mm) in 14 (82%) of 17 stents.
      CONCLUSION: CT angiography produced interpretable multiplanar images of the renal
      artery, even with a metallic stent in place, and was adequate for determining
      stent patency. Compared with catheter angiography, the intrastent luminal
      diameter was underestimated in most patients who underwent CT angiography.

PMID- 11959724
TI  - Using pullback pressure measurements to identify venous stenoses persisting after
      successful angioplasty in failing hemodialysis grafts.
AB  - OBJECTIVE: We used pullback pressure measurements to identify venous stenoses
      persisting after angioplasty of failing hemodialysis grafts. MATERIALS AND
      METHODS: Fifty angioplasty procedures were performed in 32 patients with elevated
      venous pressures at dialysis. Grafts were initially evaluated on digital
      subtraction angiography, and all stenoses measuring greater than 50% on
      angiography underwent angioplasty. In successful cases (residual stenosis < 30%),
      pullback pressure measurements were obtained from the superior vena cava to the
      graft to identify hemodynamically significant (> 10 mm Hg) stenoses. These
      lesions were then treated with repeated angioplasty. RESULTS: Hemodynamically
      significant stenoses with a gradient range of 10-27 mm Hg (mean, 16 mm Hg) were
      found in nine (18%) of 50 procedures. All gradients occurred at sites of previous
      angioplasty. Repeated angioplasty of these stenoses performed with larger
      angioplasty balloons reduced gradients to less than 3 mm Hg in six stenoses and
      to 5 mm Hg in three stenoses. In this subgroup, primary patency was eight (89%)
      of nine stenoses at 1 month and 2 months and five (56%) of nine stenoses at 6
      months. Using life table analysis, we found that primary patency of the entire
      population was 84% at 1 month, 66% at 2 months, and 47% at 6 months. The mean
      time between interventions was 6 months, and the thrombosis rate was 0.32 per
      year. CONCLUSION: Pullback pressure measurements are a useful adjunct to
      angiography to evaluate the hemodynamic results of angioplasty in patients with
      failing hemodialysis grafts.

PMID- 11959725
TI  - Balloon-occluded retrograde transvenous obliteration of gastric fundal varices
      with hemorrhage.
AB  - OBJECTIVE: This study was performed to evaluate the clinical efficacy,
      feasibility, and complications of balloon-occluded retrograde transvenous
      obliteration for patients with hemorrhage from gastric fundal varices. SUBJECTS
      AND METHODS: Between December 1994 and February 2001, 24 consecutive patients
      with hemorrhage from gastric fundal varices were enrolled in this study. Balloon
      occluded retrograde transvenous obliteration consisted of injecting 5%
      ethanolamine oleate iopamidol through the outflow vessels during balloon
      occlusion. The treatment was performed during acute bleeding in 11 patients and
      electively in 13 patients. Among those patients with acute bleeding, six were
      treated for temporary hemostasis with balloon tamponade, and five were treated
      endoscopically. RESULTS: Cannulation into the outflow vessels was performed in 23
      patients, but the balloon catheter could not be inserted in one patient who had
      inferior phrenic vein outflow. Complete success was obtained in 88% (21/24) of
      patients, and partial success was obtained in two patients. In nine of 11
      patients with acute bleeding, complete success was achieved. Rebleeding from
      gastric varices was not observed in patients treated with complete success,
      whereas two patients treated partially rebled within 1 week of the treatment
      (rate of rebleeding, 9%). Eradication of gastric varices was obtained in all
      patients (n = 19) who were examined by endoscopy 3 months after the treatment.
      Eight patients experienced worsening of esophageal varices. These patients were
      treated endoscopically because of findings that suggested a risk of hemorrhage.
      The overall mortality rate was 4% (1/24). No damage to the kidney was observed,
      although 11 patients had macrohematuria. CONCLUSION: Balloon-occluded retrograde
      transvenous obliteration followed by any hemostatic procedure might be effective
      for both prophylaxis of rebleeding and eradication of gastric fundal varices,
      even in urgent cases.

PMID- 11959726
TI  - Feasibility and effectiveness of using coronary stents in the treatment of
      hepatic artery stenoses after orthotopic liver transplantation: preliminary
      report.
AB  - OBJECTIVE: Our aim is to evaluate the feasibility, efficacy, and patency of using
      coronary stents for the treatment of hepatic artery stenosis after liver
      transplantation. CONCLUSION: Hepatic artery stenosis after liver transplantation
      can be treated using coronary stents. The low rate of complication, high
      technical success, and 1-year patency rates are encouraging.

PMID- 11959727
TI  - Potentially life-saving role for temporary endovascular balloon occlusion in
      atypical mediastinal hematoma.

PMID- 11959728
TI  - Value of dynamic contrast-enhanced MR imaging in diagnosing and classifying
      peripheral vascular malformations.
AB  - OBJECTIVE: Our purpose was to evaluate prospectively whether MR imaging,
      including dynamic contrast-enhanced MR imaging, could be used to categorize
      peripheral vascular malformations and especially to identify venous malformations
      that do not need angiography for treatment. SUBJECTS AND METHODS: In this blinded
      prospective study, two observers independently correlated MR imaging findings of
      27 patients having peripheral vascular malformations with those of diagnostic
      angiography and additional venography. MR diagnosis of the category, based on a
      combination of conventional and dynamic contrast-enhanced MR parameters, was
      compared with the angiographic diagnosis using gamma statistics. Sensitivity and
      specificity of conventional MR imaging and dynamic contrast-enhanced MR imaging
      in differentiating venous from nonvenous malformations were determined. RESULTS:
      Excellent agreement between the two observers in determining MR categories (gamma
      = 0.99) existed. Agreement between MR categories and angiographic categories was
      high for both observers (gamma = 0.97 and 0.92). Sensitivity of conventional MR
      imaging in differentiating venous and nonvenous malformations was 100%, whereas
      specificity was 24-33%. Specificity increased to 95% by adding dynamic contrast
      enhanced MR imaging, but sensitivity decreased to 83%. CONCLUSION: Conventional
      and dynamic contrast-enhanced MR parameters can be used in combination to
      categorize vascular malformations. Dynamic contrast-enhanced MR imaging allows
      diagnosis of venous malformations with high specificity.

PMID- 11959729
TI  - Echogenic polymer coating: does it improve needle visualization in
      sonographically guided biopsy?

PMID- 11959730
TI  - Removal of renal fungus balls using a mechanical thrombectomy device.

PMID- 11959731
TI  - Multidetector CT virtual bronchoscopy to grade tracheobronchial stenosis.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of noninvasive
      multidetector CT (virtual bronchoscopic images, axial CT slices, coronal
      reformatted images, and sagittal reformatted images) in depicting and allowing
      accurate grading of tracheobronchial stenosis with that of flexible bronchoscopy.
      MATERIALS AND METHODS: Multidetector CT and flexible bronchoscopy were used to
      examine 200 bronchial sections obtained from 20 patients (15 patients with
      bronchial carcinoma and five without central airways disease). Multidetector CT
      was performed using the following parameters: collimation, 4 x 2 mm, pitch,
      1.375; and reconstruction intervals, 2 mm. Postprocessing was performed using
      surface rendering and multiplanar reformatted images. CT images were
      independently interpreted by two radiologists. The tracheobronchial stenoses
      revealed on flexible bronchoscopy were graded by a pulmonologist. RESULTS:
      Virtual bronchoscopic findings, axial CT scans, and multiplanar reformatted
      images were highly accurate (98% accuracy for virtual bronchoscopic images, 96%
      for axial slices and coronal reformatted images, and 96.5% for sagittal
      reformatted images) in revealing tracheobronchial stenosis. In allowing accurate
      grading of tracheobronchial stenosis, images from virtual bronchoscopy correlated
      closely (r = 0.91) with those of flexible bronchoscopy. Because use of virtual
      bronchoscopic images reduced the overestimation of stenosis, these images allowed
      better assessment of stenosis than did axial CT slices (r = 0.84) or multiplanar
      reformatted images (r = 0.84) alone. CONCLUSION: Multidetector CT virtual
      bronchoscopy is a reliable noninvasive method that allows accurate grading of
      tracheobronchial stenosis. However, it should be combined with the interpretation
      of axial CT images and multiplanar reformatted images for evaluation of
      surrounding structures and optimal spatial orientation.

PMID- 11959732
TI  - Air trapping on CT of patients with pulmonary embolism.
AB  - OBJECTIVE: We evaluated the relationship of air trapping to mosaic perfusion in
      patients with pulmonary embolism. SUBJECTS AND METHODS: Forty-one consecutive
      patients with suspected pulmonary embolism underwent expiratory CT followed by
      helical CT angiography. After excluding 12 patients who had airway disease or
      were smokers, we divided the patients into two groups: those with (n = 15) and
      without (n = 14) pulmonary embolism. For each patient, six expiratory images were
      evaluated for the presence of air trapping, and the corresponding six images from
      CT angiography were evaluated for the presence of mosaic perfusion. Clot
      locations were assessed on CT angiography and were correlated with the presence
      of air trapping and mosaic perfusion. RESULTS: In patients with pulmonary
      embolism, mosaic perfusion was identified in 32 areas (seven patients, 46.7%),
      and air trapping was identified 68 areas (nine patients, 60%). Of the 32 areas of
      mosaic perfusion, 23 areas (71.9%) showed air trapping on expiratory CT scans. Of
      the 68 areas with air trapping on expiratory scans, 23 areas (33.8%) showed
      mosaic perfusion on inspiratory scans, and 44 areas (64.7%) had clots in the
      arteries leading to them. Clots were more frequently identified in areas of lower
      attenuation on inspiratory CT scans and air trapping (21/23) than in those of
      normal attenuation on inspiratory CT scans and air trapping (23/45) (p < 0.005).
      Only one patient without pulmonary embolism had air trapping (p < 0.005).
      CONCLUSION: Air trapping is common in pulmonary embolism and may be the cause of
      mosaic perfusion. Air trapping can be seen distal to vessels not showing
      pulmonary embolism.

PMID- 11959733
TI  - Intimal sarcoma of the pulmonary arteries seen as a mosaic pattern of lung
      attenuation on high-resolution CT.

PMID- 11959734
TI  - Preoperative MR imaging-guided needle localization of breast lesions.
AB  - OBJECTIVE: MR imaging of the breast can depict cancer that is occult on
      mammography and at physical examination. Our study was undertaken to determine
      the ease of performance and the outcome of MR imaging-guided needle localization
      and surgical excision of breast lesions. MATERIALS AND METHODS: Retrospective
      review revealed 101 consecutive breast lesions that had preoperative MR imaging
      guided needle localization with commercially available equipment, including a 1.5
      T magnet with a breast surface coil, a dedicated biopsy compression device, and
      MR imaging-compatible hookwires. Imaging studies and medical records were
      reviewed. RESULTS: Histologic findings in these 101 lesions were carcinoma in 31
      (30.7%), high-risk lesions (atypical ductal hyperplasia or lobular carcinoma in
      situ) in nine (8.9%), and benign lesions in 61 (60.4%). Fifteen (48.4%) of 31
      carcinomas were ductal carcinoma in situ, and 16 (51.6%) were infiltrating
      carcinoma (size range, 0.1-2.0 cm; median, 1.2 cm). Carcinoma was found in 16
      (45.7%) of 35 lesions detected in women with synchronous cancer, 10 (32.3%) of 31
      lesions detected on MR imaging for problem solving, and five (14.3%) of 35
      lesions detected on MR screening. The time range to perform MR imaging-guided
      localization was 15-59 min (median time, 31 min). Complications encountered in
      three cases were retained wire fragments in two and breakage of the wire tip in
      one. CONCLUSION: MR imaging-guided needle localization can be performed quickly
      and safely with commercially available equipment. The positive predictive value
      of MR imaging-guided needle localization (30.7%) was comparable to that reported
      for mammographically guided needle localization and was highest in women with
      synchronous breast cancer.

PMID- 11959735
TI  - Comparison of sitting versus prone position for stereotactic large-core breast
      biopsy in surgically proven lesions.
AB  - OBJECTIVE: Our purpose was to compare the two different body positions for
      stereotactic large-core breast biopsy with regard to sensitivity, specificity,
      and accuracy, as well as complication rate. SUBJECTS AND METHODS: Two hundred
      patients had large-core breast biopsy performed either in the prone (n = 100) or
      in the sitting (n = 100) position and subsequently underwent surgical resection.
      The histopathologic findings of large-core breast biopsy and surgery of all 200
      patients were compared; sensitivity, specificity, and accuracy were calculated
      for both groups. Biopsy-associated complications were prospectively recorded for
      immediate and delayed events and for technical failures in both groups. RESULTS:
      Sensitivity (96%), specificity (100%), and accuracy (98%) were the same for both
      groups with two false-negative findings in each group. The two false-negative
      results in the sitting group were caused by vasovagal reactions, whereas those in
      the prone group were caused by technical failure and uncomfortable biopsy
      position. More statistically significant complications (seven vs four, p < 0.001)
      and vasovagal reactions (seven vs two, p < 0.0001) were seen in the sitting
      group. CONCLUSION: For performance of large-core breast biopsy, both the prone
      and sitting positions are reliable and accurate methods. However, vasovagal
      reactions that could potentially complicate biopsy were seen significantly more
      often in the sitting position.

PMID- 11959737
TI  - MR imaging features of infiltrating lobular carcinoma of the breast:
      histopathologic correlation.
AB  - OBJECTIVE: Our study aimed to correlate the dynamic contrast-enhanced MR
      appearance of infiltrating lobular carcinoma of the breast with histopathologic
      findings. MATERIALS AND METHODS: We retrospectively reviewed the high-resolution,
      fat-suppressed and dynamic contrast-enhanced MR images of 13 of 20 women
      diagnosed with pathologically proven infiltrating lobular carcinoma of the
      breast. Twelve of the 13 women presented with breast symptoms and underwent
      mammography. Five of the women also had breast sonography. MR imaging was
      performed for evaluation of disease extent before the patients underwent modified
      radical mastectomy (n = 11) or lumpectomy (n = 2). Three experienced radiologists
      reviewed the MR scans. The tumor pattern types described on imaging were
      correlated with a detailed analysis of the pathology. RESULTS: We found three
      patterns of infiltrating lobular carcinoma on MR imaging. The tumor pattern on
      imaging correlated with pathologic tumor morphology. We found the following
      patterns of infiltrating lobular carcinoma: a solitary mass with irregular
      margins (n = 4) that corresponded to the same appearance at pathology; multiple
      lesions, either connected by enhancing strands (n = 6) or separated by
      nonenhancing intervening tissue (n = 2), that correlated with the pathologic
      appearance of noncontiguous tumor foci, with malignant cells streaming in single
      file fashion in the breast stroma or small tumor aggregates separated by normal
      tissue; and enhancing septa only, which were correlated with the histopathologic
      appearance of tumor cells streaming in the breast stroma (n = 1). CONCLUSION:
      Infiltrating lobular carcinoma may be detected on MR imaging as solitary or
      multiple lesions that correspond to tumor morphology on pathologic examination.
      The appearance of multiple lesions or of enhancing fibroglandular breast elements
      on MR imaging is suggestive of infiltrating lobular carcinoma.

PMID- 11959738
TI  - Lupus mastitis: radiologic and pathologic features.

PMID- 11959739
TI  - Aspergilloma of the breast in a woman with acute myeloid leukemia.

PMID- 11959740
TI  - Occult fractures of the waist of the scaphoid: early diagnosis by high-spatial
      resolution sonography.
AB  - OBJECTIVE: This study evaluated the diagnostic accuracy of high-spatial
      resolution sonography in the diagnosis of occult fractures of the waist of the
      scaphoid. SUBJECTS AND METHODS: Sonography of the scaphoid bone with a 12-MHz
      transducer was performed in 54 patients with clinically suspected scaphoid
      fracture and normal findings on initial radiographs, including specific scaphoid
      images. Three levels of clinical suspicion were considered: high (20%), moderate
      (30%), and low (50%). Attention was paid to the continuity of the scaphoid cortex
      and to the surrounding soft tissues (i.e., hemarthrosis or hematoma). Data from
      early sonograms were then compared with the results of radiography repeated 10-14
      days after the initial trauma. In cases of persistent suspicion despite normal
      findings on follow-up radiographs, the presence of fracture was evaluated on CT
      (four patients), MR imaging (one patient), or bone scanning (one patient).
      RESULTS: Follow-up examinations proved fracture of the scaphoid waist in five
      patients. In all patients, diagnosis of fracture was suspected on initial
      sonograms showing cortical disruption associated with soft-tissue abnormalities.
      There was one false-positive finding and no false-negative results. Using
      cortical disruption as a diagnostic criterion, we found the sensitivity,
      specificity, and accuracy of high-resolution sonography for the depiction of
      scaphoid fracture to be 100%, 98%, and 98%, respectively. Using soft-tissue
      abnormalities alone as a criterion, we found the sensitivity, specificity, and
      accuracy of high-resolution sonography to be 100%, 65%, and 68%, respectively.
      The overall prevalence of occult fracture was 9%, ranging from 3.7% for low
      suspicion to 27% for high suspicion of fracture. CONCLUSION: High-resolution
      sonography is a reliable and accurate method of evaluating occult fractures of
      the scaphoid waist. Cortical disruption is the diagnostic key. Soft-tissue
      abnormalities alone lack specificity.

PMID- 11959741
TI  - Artifacts, anatomic variants, and pitfalls in sonography of the foot and ankle.

PMID- 11959742
TI  - Intramuscular myxoma: characteristic MR imaging features.
AB  - OBJECTIVE: The purpose of our study was to identify the characteristic MR imaging
      features of intramuscular myxoma. MATERIALS AND MATERIALS: We retrospectively
      reviewed the MR imaging features of 20 patients with intramuscular myxoma.
      Clinical assessment included the age and sex of the patient and location of the
      tumor. Radiologic evaluation included the lesion size and shape, border
      definition, signal on T1- and T2-weighted or fluid-sensitive MR sequences,
      enhancement pattern, presence or absence of a fat rind, and presence or absence
      of increased signal in the adjacent muscle on T2-weighted or fluid-sensitive MR
      sequences. RESULTS: The mean age of patients presenting with intramuscular myxoma
      was 61 years (range, 15-85 years; median, 64 years). The mean lesion size was 6.9
      cm (range, 3-17 cm; median, 6.3 cm). A peritumoral fat rind was present in 13 of
      the patients (65%) with myxoma, and an increased signal in the adjacent muscle on
      fluid-sensitive sequences was present in 11 patients (55%). Intramuscular myxomas
      were homogeneously low in signal intensity on T1-weighted MR sequences in 19
      patients (95%), with all lesions showing a high signal intensity on T2-weighted
      or fluid-sensitive MR sequences. Twelve of the myxomas had well-defined borders,
      and eight had borders that were partially ill defined. Of the 11 lesions imaged
      after gadolinium administration, six (55%) showed intense heterogeneous
      enhancement. CONCLUSION: Findings of a mass that on MR images shows a
      perilesional fat rind, the signal intensity of fluid, and an increased signal in
      the adjacent muscle on T2-weighted or fluid-sensitive MR sequences are strongly
      suggestive of intramuscular myxoma. The degree of lesion enhancement varies but
      is most frequently intense and heterogeneous. Although the recognition of these
      features likely will not obviate biopsy of any individual lesion, it will allow
      more accurate prebiopsy diagnosis and preoperative planning.

PMID- 11959743
TI  - Radiologic and clinical spectrum of occipital condyle fractures: retrospective
      review of 107 consecutive fractures in 95 patients.
AB  - OBJECTIVE: We proposed to characterize the radiologic spectrum of occipital
      condyle fractures in a large series of patients and to correlate fracture
      pathology with neurosurgical treatment and patient outcome. MATERIALS AND
      METHODS: We conducted a retrospective review of the findings on conventional
      radiography, CT, and MR imaging in 95 patients with 107 occipital condyle
      fractures. We described fracture patterns according to two previously published
      classification systems. Clinical findings, neurosurgical management, and patient
      outcome were obtained from the medical records. RESULTS: Inferomedial avulsions
      (Anderson and Montesano type III) were the most common type of occipital condyle
      fracture, constituting 80 (75%) of 107 overall fractures. Unilateral occipital
      condyle fractures were found in 73 (77%) of 95 patients, and 58 patients were
      treated nonoperatively; occipitocervical fusion was required in nine patients for
      complex C1-C2 injuries, and six patients died. Bilateral occipital condyle
      fractures or occipitoatlantoaxial joint injuries were seen in 22 (23%) of 95
      patients. Occipitocervical fusion or halo traction for the craniocervical
      junction was required in 12 patients, all of whom had CT evidence of bilateral
      occipitoatlantoaxial joint disruption and six of whom showed normal
      craniocervical relationships on conventional radiographs. Six patients with
      nondisplaced fractures were treated nonoperatively, and four patients died.
      Thirty (32%) of 95 patients showed continued disability, whereas 55 (57.5%) of 95
      patients had good outcomes at 1 month. Associated cervical spine injuries were
      present in 29 (31%) of 95 patients. CONCLUSION: Given their associated traumatic
      brain and cervical spine injuries, occipital condyle fractures are markers of
      high-energy traumas. That conventional radiographs alone may miss up to half of
      the patients with acute craniocervical instability has not been well established.
      Avulsion fracture type and fracture displacement are associated with both injury
      mechanism and the need for surgical stabilization. In this series, most
      unilateral occipital condyle fractures were treated nonoperatively, whereas
      bilateral occipitoatlantoaxial joint injuries with findings of instability
      usually required surgical stabilization.

PMID- 11959744
TI  - Aberrant subclavian arteries: cross-sectional imaging findings in infants and
      children referred for evaluation of extrinsic airway compression.
AB  - OBJECTIVE: The purpose of our study was to describe patterns of airway
      compression identified on cross-sectional imaging in infants and children with
      either right aortic arch and aberrant left subclavian artery or left aortic arch
      with aberrant right subclavian artery. MATERIALS AND METHODS: Data from MR
      imaging and CT performed to evaluate pediatric patients for extrinsic airway
      compression were reviewed for cases that revealed an aberrant right or left
      subclavian artery. Clinical, endoscopic, and imaging findings in identified cases
      were reviewed. Recurrent patterns of extrinsic compression were reviewed among
      cases. RESULTS: Twelve patients with right aortic arch with aberrant left
      subclavian artery and nine patients with left aortic arch and aberrant right
      subclavian artery were identified. All 12 with right aortic arch with aberrant
      left subclavian artery had airway compression shown, with multiple sites or
      diffuse compression in six. Of these 12 patients, nine had compression at the
      level of the arch and aberrant subclavian artery (10 had Kommerell's
      diverticulum), and nine had compression of the distal airway in association with
      a midline descending aorta. Five of the nine patients with left aortic arch and
      aberrant right subclavian artery had airway compression shown, all at the level
      of the arch and aberrant subclavian artery. None of these compressions was
      associated with either Kommerell's diverticulum or midline descending aorta.
      CONCLUSION: Both right and left aberrant subclavian arteries can be associated
      with symptomatic airway compression, but the patterns of compression are
      different. The airway compression in right aortic arch with aberrant left
      subclavian artery is often associated with either Kommerell's diverticulum or
      midline descending aorta, whereas compression associated with left aortic arch
      and aberrant right subclavian artery is not.

PMID- 11959745
TI  - Imaging findings in pediatric patients with persistent airway symptoms after
      surgery for double aortic arch.
AB  - OBJECTIVE: The purpose of this study was to review the imaging findings of
      children referred for cross-sectional imaging to evaluate persistent airway
      symptoms after surgical therapy for double aortic arch. CONCLUSION: Airway
      narrowing is clearly shown on cross-sectional imaging in patients with persistent
      airway symptoms after surgical therapy for double aortic arch. Two patterns of
      airway compression are typically seen: narrowing of the trachea at the level of
      the postsurgical arch and narrowing of the left main bronchus as a result of
      compression from a midline descending aorta. Both patterns may be seen in
      patients regardless of whether the left or the right arch has been ligated.

PMID- 11959746
TI  - MR imaging of popliteal pterygium syndrome in pediatric patients.
AB  - OBJECTIVE: Our purpose was to describe the use of MR imaging in the evaluation of
      the positions of the popliteal artery and peroneal nerve in children with
      popliteal pterygium syndrome for preoperative planning and to describe the
      typical appearance of popliteal pterygium on MR imaging. CONCLUSION: By depicting
      the popliteal artery and peroneal nerve either in normal positions or abnormally
      located immediately adjacent to the pterygium, MR imaging provides useful
      information for preoperative planning in children with popliteal pterygium
      syndrome. The MR appearance of a popliteal pterygium is that of a band of
      abnormal tissue extending from the ischium to the os calcis that has signal
      characteristics of fibrous tissue often attached to a belly of anomalous muscle.

PMID- 11959748
TI  - CT of pregnant women for urinary tract calculi, pulmonary thromboembolism, and
      acute appendicitis.

PMID- 11959749
TI  - Magic angle effect in articular cartilage.

PMID- 11959750
TI  - Chopped liver...all over again.

PMID- 11959751
TI  - Free "PowerPointing".

PMID- 11959752
TI  - Metformin hydrochloride in patients undergoing myelography.

PMID- 11959753
TI  - Bone scintigraphy reveals a solid and papillary epithelial neoplasm of the
      pancreas.

PMID- 11959754
TI  - Emphysematous gastritis associated with gastric infarction in a patient with
      adult polycystic renal disease: CT diagnosis.

PMID- 11959755
TI  - Gastroduodenal mucosal prolapse: diagnosis using conventional abdominal
      radiographs.

PMID- 11959756
TI  - Enterolith around a migrated biliary stent.

PMID- 11959757
TI  - Contraceptives, pregnancy, and RA.

PMID- 11959758
TI  - Case Number 23: Tuberculous tenosynovitis.

PMID- 11959759
TI  - Sarcoidosis: TB or not TB?

PMID- 11959760
TI  - Calcium apatite crystals in synovial fluid rice bodies.
AB  - BACKGROUND: Rice bodies can occur in the joints in many rheumatic conditions, but
      they are most common in rheumatoid arthritis. They are generally believed to
      occur rarely in patients with osteoarthritis, but one study reported rice bodies
      with apatite crystals. OBJECTIVE: To report on a series of joint fluids with rice
      bodies containing apatite clumps and examine their clinical pictures. METHODS:
      All synovial fluid analysis reports for 10 years were reviewed for rice bodies
      and eight patients were reported on. A series of patients with a variety of
      diseases with synovial fluid rice bodies found to contain calcific material is
      described. All were examined by compensated polarised light and alizarin red
      stain, and four were examined by electron microscopy. RESULTS: The eight patients
      all had alizarin red S chunks embedded throughout the rice body. Transmission
      electron microscopy disclosed the presence of a matrix of collagen, fibrin, and
      amorphous materials containing typical apatite crystals. Clinical diagnoses,
      radiographic findings, and leucocyte counts varied, but six of the eight patients
      had had previous repeated corticosteroid injections into the joints. CONCLUSION:
      Aggregates of apatites may be more common than previously recognised in rice
      bodies as they are not routinely sought. Whether they are a result of joint
      damage or depot steroid injections and whether that might contribute to further
      joint injury now needs to be investigated.

PMID- 11959761
TI  - Characterisation of the cell type-specificity of collagenase 3 mRNA expression in
      comparison with membrane type 1 matrix metalloproteinase and gelatinase A in the
      synovial membrane in rheumatoid arthritis.
AB  - OBJECTIVE: To study the pattern and cell type-specificity of collagenase 3,
      membrane-type 1 matrix metalloproteinase (MT1-MMP), and gelatinase A mRNA
      expression in the synovial membrane in rheumatoid arthritis (RA). METHODS: The
      mRNA expression of collagenase 3, MT1-MMP, and gelatinase A was characterised by
      northern blot analysis, reverse transcriptase-polymerase chain reaction, and in
      situ hybridisation. In situ hybridisation was performed in combination with the
      immunohistochemical detection of cell type-specific antigens. RESULTS: Synovial
      membrane specimens from 19 of 21 patients with RA expressing collagenase 3 mRNA
      were positive for MT1-MMP and gelatinase A mRNA. In control samples from patients
      without destructive inflammatory joint diseases collagenase 3 mRNA was not
      expressed and only in two of seven cases was a coexpression of MT1-MMP and
      gelatinase A mRNA detected. Fibroblast-like cells of the synovial membrane were
      found to be the predominant source of collagenase 3, MT1-MMP, and gelatinase A
      mRNA expression in lining and sublining layers as well as at the synovial
      membrane-cartilage interface. Additionally, the expression of MT1-MMP mRNA was
      detected in endothelial cells. Collagenase 3 mRNA expression was found in about
      5% of CD68 positive macrophages. CONCLUSIONS: Collagenase 3 mRNA is expressed
      simultaneously with MT1-MMP and gelatinase A mRNA in fibroblast-like cells of the
      synovial membrane in RA. These results suggest (a) a broad extracellular
      proteolytic potential of fibroblast-like cells and (b) an important role of cell
      surface associated procollagenase 3 activation by MT1-MMP and gelatinase A for
      cartilage degradation by invading fibroblast-like cells.

PMID- 11959762
TI  - Clinical, immunological, and immunogenetic aspects of autoantibody production
      against Ro/SSA, La/SSB and their linear epitopes in primary Sjogren's syndrome
      (pSS): a European multicentre study.
AB  - OBJECTIVES: To investigate the clinical and immunogenetic aspects of antibody
      formation against Ro/SSA and La/SSB as well as their linear B cell epitopes in
      patients with primary Sjogren's syndrome (pSS) from different European countries.
      PATIENTS AND METHODS: Ninety patients with pSS from six European centres were
      studied. Serum samples from all patients were tested in a control laboratory for
      anti-Ro/SSA and anti-La/SSB autoantibodies by RNA precipitation assay and
      autoantibodies to the previously reported B cell linear epitopes of Ro 60 kDa
      (p169-190aa and p211-232aa) and La/SSB (p147-154aa, p291-302aa, p301-318aa, and
      p349-364aa). DNA from 88 patients was used for the determination of HLA-DRB1, 
      DQA1, and -DQB1 genotypes. Analysis of the results was performed in the 88
      patients who were genotyped and tested also for antipeptide antibodies. RESULTS:
      Antibodies to B cell epitopes of Ro 60 kDa were detected at a low frequency
      (range 10-37%). In contrast, B cell epitopes of La/SSB were detected frequently
      (range 58-86%) among the anti-La/SSB positive sera. Autoantibodies to the La/SSB
      epitope, p349-364aa, were significantly positively associated with longer disease
      duration (p<0.05), recurrent or permanent parotid gland enlargement (p<0.005),
      and a higher proportion of non-exocrine manifestations (p<0.005), compared with
      patients without autoantibodies. The presence of anti-Ro/SSA and anti-La/SSB
      autoantibodies was significantly associated with the presence of HLA-DRB1*03 and
      DQB1*02 (p=0.038 and p=0.034, respectively). This association was even more
      prominent and extended to HLA-DQA1*0501 when patients were stratified according
      the presence of autoantibodies to discrete La/SSB B cell epitopes in comparison
      with autoantibody negative patients (p<0.01). They were found also to be highly
      associated with the alleles HLA-DQB1*02 and HLA-DQA1*0501 as well as the presence
      of a shared amino acid motif in the region 59-69aa of DQB1 first domain (p<0.01,
      respectively). CONCLUSIONS: Autoantibodies against La/SSB, binding to four
      synthetic peptides, derived from the sequence of the La protein were identified
      with increased frequency in sera of patients with pSS. The formation of
      autoantibodies against B cell epitope analogues of La/SSB in European patients
      with pSS may be dependent on the presence of a permissive HLA-DQ heterodimer,
      most prominently represented by the HLA-DQA1*0501/DQB1*0201 heterodimer,
      suggesting that a model of HLA restricted presentation of La/SSB peptide
      determinants is crucial for the autoimmune response against La/SSB.

PMID- 11959763
TI  - Pregnancy and oral contraceptive use do not significantly influence outcome in
      long term rheumatoid arthritis.
AB  - BACKGROUND: Oral contraceptives (OC) and pregnancy are known to have an influence
      on the risk of onset of rheumatoid arthritis (RA). Pregnancy itself has
      beneficial effects on the activity of the disease, with relapses post partum. It
      is not known, however, whether OC and pregnancies influence the ultimate outcome
      of RA. OBJECTIVES: To explore whether OC use and pregnancies influence the 12
      year outcome in RA as measured by radiological damage and disability. METHODS: In
      a prospective inception cohort of 132 female patients with recent RA according to
      the 1987 American College of Rheumatology criteria-a cohort initially gathered to
      study the association between hormonal factors and the onset of RA-outcome was
      assessed in a follow up after 12 years. The outcome was evaluated in 112 (85%)
      women by the radiological damage of hands and feet as measured with the Sharp
      score modification van der Heijde (SHS), the damage of the large joints measured
      with the Larsen score (LS) of large joints (0-60), and the disability measured
      with the Health Assessment Questionnaire (HAQ). The median values of each outcome
      variable were calculated for several subgroups of patients stratified for OC use
      and pregnancies before and after onset of the disease and the tertiles of the
      total number of months of OC use and of pregnancies. The association of OC use
      and pregnancies before and after onset of the disease with the outcome variables
      was calculated using Spearman's rank correlation (r(s)). The combined influence
      of OC use and pregnancies on the SHS, LS, and HAQ at 12 years was estimated using
      ordinal polytomous logistic regression. RESULTS: The median values of the SHS,
      LS, and HAQ showed a trend towards less radiological joint damage and less
      disability in women with long term OC use and multiple pregnancies. This
      difference, however, was not significant, except for the HAQ score in women with
      three or more pregnancies in life. There was no association between pregnancies,
      however defined, and any parameter of RA outcome after 12 years (maximum r(s)=
      0.10). The only significant correlation was found between OC use before symptom
      onset and the LS (r(s)=-0.22, p<0.05). The combination of hormonal variables
      explained no more than a maximum of 3% of the variance of the 12 year outcome as
      measured by the SHS. CONCLUSION: OC use and pregnancy do not significantly
      influence outcome in long term RA. There is, however, a trend for patients with
      multiple pregnancies and long term OC use to have less radiographic joint damage
      and a better functional level.

PMID- 11959764
TI  - Outcome of a cohort of 300 patients with systemic lupus erythematosus attending a
      dedicated clinic for over two decades.
AB  - OBJECTIVE: To examine the mortality rate and causes of death in a cohort of 300
      patients with systemic lupus erythematosus (SLE). METHODS: A retrospective
      analysis was performed on all patients attending the SLE clinic between 1978 and
      2000. Information was obtained on those patients lost to follow up. Cause of
      death was analysed and categorised as early (<5 years after diagnosis of SLE) and
      late (>5 years after diagnosis of SLE). Standardised mortality rates were
      obtained. RESULTS: The patients were followed up for a median of 8.3 years.
      Seventy three (24%) patients were no longer followed up at the end of the study
      period, of whom 41 (14%) had died. Of the 32 patients lost to follow up, 14 were
      being actively followed up within the UK, 16 were followed up outside the UK, and
      two patients were untraceable. The most common cause of death was malignancy,
      which accounted for eight (20%) deaths, followed by infection and vascular
      disease, which accounted for seven (17%) deaths each. CONCLUSIONS: Malignancy was
      the most common cause of death. Cause of death varied depending on disease
      duration. Forty per cent of early deaths were due to SLE related renal disease,
      whereas 23% of late deaths were due to vascular causes. Death due to infection
      occurred throughout the follow up period. There was a fourfold increased risk of
      death in our cohort of patients with SLE compared with the general population.

PMID- 11959765
TI  - Critical illness in systemic lupus erythematosus and the antiphospholipid
      syndrome.
AB  - OBJECTIVES: To investigate the causes, course, and outcome of critical illness
      requiring emergency admission to the intensive care unit (ICU) in patients with
      systemic lupus erythematosus (SLE) or the antiphospholipid syndrome (APS), or
      both. METHODS: Critically ill patients with SLE or APS, or both, admitted to a
      London teaching hospital ICU over a 15 year period were studied. Demographic,
      diagnostic, physiological, laboratory, and survival data were analysed. Kaplan
      Meier survival curves were constructed by age, time from first diagnosis of SLE,
      and time from first ICU admission. The log rank test and a backwards stepwise Cox
      regression were used to identify factors associated with reduced survival.
      RESULTS: Sixty one patients with SLE alone (39%) and/or APS (61%) required 76
      emergency admissions to the ICU. Patients had high severity of illness scores
      (median APACHE II 22 (range 8-45)) and multiorgan dysfunction. The primary
      diagnoses for patients admitted were infection in 31/76 (41%), renal disease in
      16/76 (21%), cardiovascular disease in 12/76 (16%), and coagulopathies in 11/76
      (14%). The commonest secondary diagnosis was renal dysfunction (49%). Factors
      associated with an increased risk of death were cyclophosphamide before
      admission, low white cell count, and high severity of illness score. Before
      adjustment for these factors renal disease had a strong adverse effect on long
      term survival (analysis by age at diagnosis p=0.005, analysis by time since first
      ICU admission, p=0.07). After adjustment, infection at admission to ICU was
      associated with an increased ICU mortality (p=0.02) and was the cause of death in
      13/17 patients who died in the ICU. Similarly, after adjustment, APS was
      associated with reduced ICU survival (p=0.1) and reduced long term (p=0.03)
      survival. Seventeen patients (28%) died in the ICU, and 31 patients (51%) had
      died by the last follow up. Median time from ICU admission to death was four
      years. Overall five year survival from the first ICU admission was 43%.
      CONCLUSION: Critical illness requiring ICU admission may occur in patients with
      SLE and APS. In this study, ICU survival was better than previously described,
      but long term survival was poor. Cyclophosphamide administration, low white cell
      count, and high severity of illness score were associated with reduced survival.
      Before adjustment for these factors, only renal disease had an adverse effect on
      outcome but after adjustment, infection and APS reduced survival.

PMID- 11959766
TI  - Effect of pain reduction on postural sway, proprioception, and quadriceps
      strength in subjects with knee osteoarthritis.
AB  - OBJECTIVE: To investigate whether alleviation of knee pain influences quadriceps
      function, proprioceptive acuity, and postural stability in patients with knee
      osteoarthritis (OA). METHODS: A crossover, within-subject, double blind study
      design involving 68 subjects with painful knee OA. Each subject received an intra
      articular injection into one or both knees (both if symptomatic) of either 5 ml
      0.5% bupivacaine or 5 ml 0.9% saline. Two weeks later they received an injection
      of the alternative agent. Subjects and observer were unaware of the order of
      injection, which was randomly assigned. Knee pain (100 mm visual analogue scale),
      static postural sway, knee proprioceptive acuity, maximum voluntary contraction
      (MVC), and percentage activation of the quadriceps were assessed immediately
      before and one hour after each injection. RESULTS: Significant pain reduction was
      achieved one hour post-bupivacaine (mean difference as a percentage change 56.85,
      95% CI 31.01 to 73.65; p<0.001) and post-saline (mean difference as a percentage
      change 41.94, 95% CI 11.57 to 76.66; p< 0.001), with no significant difference
      between the two. Both MVC and activation increased significantly post-bupivacaine
      (mean percentage differences 18.83, 95% CI -31.79 to -0.26, and -11.90, 95% CI 
      39.53 to 2.97, respectively; both p<0.001) and post-saline (mean percentage
      differences -7.64, 95% CI -21.96 to 4.73, and -10.71, 95% CI -25.19 to 2.60
      respectively; both p<0.001). Proprioception worsened after bupivacaine (mean
      percentage difference -28.15%, 95% CI -83.47 to 19.74; p=0.009), but there was no
      effect on postural sway; saline injection had no effects. There was no order
      effect, and comparison of median percentage changes showed no significant
      differences between injections for change in MVC, activation, proprioception, or
      sway. CONCLUSION: Reduction in knee pain through either peripheral (local
      anaesthetic) or central (placebo) mechanisms resulted in increased MVC. This
      increase, however, did not result in improvements in proprioception or static
      postural stability, suggesting that other mechanisms play a part in these
      functions, at least in this acute model.

PMID- 11959767
TI  - Work status and productivity costs due to ankylosing spondylitis: comparison of
      three European countries.
AB  - OBJECTIVE: To compare work disability, sick leave, and productivity costs due to
      ankylosing spondylitis (AS) of three European countries. METHODS: 216 patients
      with AS from the Netherlands, France, and Belgium participated in a two year
      observational study. Employment and work disability rates at baseline were
      adjusted for age and sex. Productivity costs were calculated by both the friction
      cost method and the human capital approach. The adjusted contributions of country
      to employment, work disability, and having an episode of sick leave were assessed
      by logistic regression and the contribution of the country to days of sick leave
      and costs by Cox proportional hazard analysis. RESULTS: 209 patients completed
      the two years' follow up with sufficient data for cost analysis. Adjusted
      employment was 55% in the Netherlands as compared with 72% in both other
      countries and only in the Netherlands was it lower than expected in the general
      population. Adjusted work disability was 41%, 23%, and 9% in the Netherlands,
      France, and Belgium and in all countries was higher than expected in the general
      population. In those with a paid job, the mean number of days of sick leave per
      patient per year because of AS was 19 (range 0-130), six (range 0-77), and nine
      (range 0-60 ) in the Netherlands, France, and Belgium respectively. Applying the
      friction cost method to those with a paid job resulted in mean costs per patient
      per year of 1257 euros (range 0-7356), 428 euros (range 0-5979), and 476 euros
      (range 0-2354) in the Netherlands, France, and Belgium. Applying the human
      capital approach to the whole group resulted in mean costs per patient per year
      of 8862 euros (range 0-46 818), 3188 euros (range 0-43 550), and 3609 euros
      (range 0-34 320) in the three countries, respectively. After adjusting for
      sociodemographic and disease characteristics, living in the Netherlands, as
      compared with both other countries, was associated with a higher chance of being
      work disabled (odds ratio (OR)=3.82; 95% confidence interval (CI) 1.33 to 11.01),
      but not with the risk of having an episode of sick leave. Similarly, living in
      the Netherlands contributed independently to the number of days sick leave
      (OR=0.65; 95% CI 0.43 to 0.97), a higher amount of friction costs (OR=0.63; 95%
      CI 0.42 to 0.96), and a higher amount of human capital costs (OR=0.46; 95% CI
      0.32 to 0.68). CONCLUSION: There are remarkable differences in work status and
      productivity costs between the three European countries. This has implications
      for the generalisability of health economic studies.

PMID- 11959769
TI  - Delayed examination of synovial fluid by ordinary and polarised light microscopy
      to detect and identify crystals.
AB  - OBJECTIVE: To determine the reliability of a delay in the microscopic examination
      of synovial fluid (SF) to detect and identify crystals. METHODS: Ninety one SF
      samples were examined, 31 with monosodium urate (MSU) crystals, 30 with crystals
      of calcium pyrophosphate dihydrate (CPPD), and 30 containing no crystals. The
      specimens were stored with EDTA, sodium heparin, and without anticoagulant at 4
      degrees C before examination at 24 and 72 hours with ordinary and polarised light
      microscopy. Another aliquot of the same samples was stored in a plastic container
      without anticoagulant at -80 degrees C and examined after two months. RESULTS:
      When the samples stored at 4 degrees C were re-examined after 24 hours,
      intracellular crystals of MSU were seen in 90/93 (97%) cases where they had been
      identified previously and 89/93 (96%) cases after 72 hours. Similarly, CPPD
      crystals were identified in 90/90 (100%) and 87/90 (97%) cases after 24 and 72
      hours. Examination of the samples stored at -80 degrees C showed intracellular
      MSU crystals in 25/31 (81%) of cases and CPPD crystals in 25/30 (83%). No
      crystals were seen in any sample which had previously been diagnosed as crystal
      free. CONCLUSIONS: Deferred microscopic examination of refrigerated or deep
      frozen SF provides a strong probability of detecting MSU or CPPD crystals if
      these are present initially.

PMID- 11959768
TI  - gammadelta T cell subsets in patients with arthritis and chronic neutropenia.
AB  - BACKGROUND: An abnormal distribution of subsets of gammadelta T cells, which are
      a component of the inflammatory infiltrate in arthritic synovium, has been
      demonstrated in the peripheral blood (PB) of patients with arthritis and
      neutropenia. OBJECTIVE: To evaluate whether the clinical manifestations of
      patients with arthritis and neutropenia are related to the specific gammadelta T
      cell subset predominant in the PB. METHODS: Flow cytometry of PB lymphocytes in
      six consecutive patients with chronic neutropenia and arthritis was performed.
      Variable (V) gamma and delta gene families were analysed by polymerase chain
      reaction. cDNA was subjected to direct automated sequencing of T cell receptor
      (TCR) genes. RESULTS: Three patients had non-deforming and non-erosive rheumatoid
      factor (RF)(+) polyarticular rheumatoid arthritis, RF(+) oligoarticular
      arthritis, or RF(-) non-deforming oligoarticular psoriatic arthritis with
      persistent expansions of Vgamma1(+)/Vdelta2(+), Vgamma2(+)/Vdelta2(+), or
      Vgamma1(+)/Vdelta (undetermined (2- 1-)) T cells, respectively. The other three
      patients, without persistent expansion of gammadelta T cells, had either non
      deforming and non-erosive oligo- or polyarthritis with a balanced distribution of
      several Vdelta and Vgamma genes, or severe erosive RF(+) arthritis with
      deficiency of all but Vgamma1(+)/Vdelta1(+) T cells. CONCLUSIONS: gammadelta T
      cell lymphoproliferations in chronic neutropenia and arthritis use different
      Vgamma and Vdelta gene families, often forming T cell receptor (TCR) structures
      that are infrequent in normal adult PB. Arthritis with Vgamma1(+)/Vdelta2(+),
      Vgamma2(+)/Vdelta2(+), or Vgamma1(+)/Vdelta2(-)/Vdelta1(-) gammadelta T cells in
      the PB is non-deforming and non-erosive, suggesting a protective effect of these
      cells, as opposed to a more pathogenic contribution of Vgamma1(+)/Vdelta1(+)
      cells.

PMID- 11959770
TI  - Comparison of rheumatological and gastrointestinal symptoms after infection with
      Campylobacter jejuni/coli and enterotoxigenic Escherichia coli.
AB  - OBJECTIVES: To estimate the incidence of postinfectious joint complaints after
      Campylobacter jejuni/coli enteritis compared with enteritis caused by
      enterotoxigenic E coli (ETEC). To compare gastrointestinal symptoms, antibiotic
      treatment, and antibody levels among patients with and without joint symptoms.
      METHOD: Questionnaires were sent to 210 consecutive patients with Campylobacter
      infection and an equal number of patients with E coli (ETEC). Blood samples for
      anti-Campylobacter antibodies were collected after two weeks, three months, six
      months, and two years. RESULTS: Twenty seven of 173 (16%) patients with
      Campylobacter and 10/177 (6%) with E coli (ETEC) reported joint symptoms
      (p=0.004). In the Campylobacter group duration of diarrhoea was a median of 13
      days for patients with arthralgia and seven days for those without joint pain
      (p=0.0058). Patients with E coli had diarrhoea of longer duration than patients
      infected with Campylobacter (14 days v seven days; p=0.0005). E coli patients had
      fewer gastrointestinal symptoms than Campylobacter patients (p=0.0001). Fifty
      nine per cent of Campylobacter patients with joint pain had received antibiotic
      treatment because of enteritis compared with 26% with enteritis only (p=0.03).
      Campylobacter species and serotypes were equally distributed in both groups and
      there was no difference in anti-Campylobacter antibody levels between the groups.
      CONCLUSION: There was a significantly increased risk of developing joint symptoms
      after contracting Campylobacter infection compared with E coli. Campylobacter
      patients with joint pain had more severe gastrointestinal symptoms and longer
      duration of diarrhoea. Antibiotic treatment does not seem to prevent reactive
      joint symptoms. Levels of anti-Campylobacter antibodies were the same in both
      groups.

PMID- 11959771
TI  - Prevalence of rheumatic diseases in a rheumatological outpatient practice.
AB  - OBJECTIVE: To assess the prevalence and distribution of rheumatic diseases in a
      community based rheumatological outpatient practice. METHODS: Rheumatological
      diagnoses of 3751 consecutive new and returning patients were recorded using a
      standard diagnosis form. RESULTS: 6264 rheumatological diagnoses were made in
      3751 patients, of whom 1097 were newly referred; 69% of all patients were female.
      Inflammatory joint and spine diseases were diagnosed in 42% of all patients
      (including 5% with connective tissue diseases), soft tissue rheumatism in 37%,
      degenerative joint and spine diseases in 36%, and metabolic bone diseases in 17%
      of all patients. In new patients soft tissue rheumatism was most prevalent (51%),
      45% had osteoarthritis, 24% had inflammatory joint and spine disease (including
      2% with connective tissue disease), and 13% had metabolic bone disease. One of 10
      new patients was diagnosed with definite rheumatoid arthritis. In returning
      patients the prevalence of inflammatory rheumatic diseases was higher (49%,
      including 6% with connective tissue diseases). 28% of the returning patients had
      rheumatoid arthritis. Osteoarthritis was present in 33% and metabolic bone
      disease in 19% of the returning patients. CONCLUSIONS: Soft tissue rheumatism and
      degenerative joint and spine diseases are the most common rheumatological
      diagnoses in newly referred patients visiting a community based rheumatological
      outpatient practice. Inflammatory rheumatic diseases were most prevalent in
      returning patients.

PMID- 11959772
TI  - Relationship of hypovitaminosis D and secondary hyperparathyroidism with bone
      mineral density among UK resident Indo-Asians.
AB  - BACKGROUND: There is a high prevalence of vitamin D deficiency in UK resident
      Indo-Asians and this may be complicated by secondary hyperparathyroidism.
      OBJECTIVE: To investigate the relationship between these conditions and bone
      mineral density (BMD) in Indo-Asian rheumatology patients. METHODS: 110 Indo
      Asian patients presenting to a general rheumatology clinic were selected for the
      study, of whom 77 were vitamin D deficient (HD), and 33 also had associated
      secondary hyperparathyroidism (HD-SHPT). BMD measurements at the femoral neck
      (FN), lumbar spine (LS), distal radius (DR), and radius 33% were obtained. T and
      Z scores were used in the evaluation of the dual energy x ray absorptiometry
      findings. The Mann-Whitney U test and chi(2) tests were used in the statistical
      analysis. RESULTS: The patients with HD-SHPT had significantly lower serum 25-OH
      vitamin D, higher serum alkaline phosphatase, and lower calcium levels than the
      HD group. Both T and Z scores failed to show any significant difference between
      the groups in the LS, but patients with HD-SHPT compared with those with HD had
      significantly lower FN T scores (-1.05 (1.47) v 0.28 (1.22), p=0.003), FN Z
      scores (-0.45 (1.27) v 0.26 (0.96), p=0.001), DR T scores (-1.83 (1.82) v -0.44
      (1.77), p<0.001), DR Z scores (-1.25 (1.44) v -0.08 (1.6), p=0.001), radius 33% T
      scores (-1.65 (1.66) v -0.79 (1.21), p=0.008), and radius 33% Z scores (-1.07
      (1.28) v -0.44 (1.1), p=0.017). CONCLUSION: Hypovitaminosis D complicated by
      secondary hyperparathyroidism is associated with significantly decreased bone
      mineral density.

PMID- 11959773
TI  - Humoral and cell mediated immune response to cow's milk proteins in Behcet's
      disease.
AB  - OBJECTIVE: To investigate the humoral and cellular immune response against cow's
      milk proteins in Behcet's disease and to distinguish any behaviour during active
      or inactive disease. METHODS: Peripheral blood mononuclear cells from 16 patients
      and from eight normal controls were cultured in the presence of
      phytohaemagglutinin (PHA), beta-casein, beta-lactoglobulin, or chicken egg
      albumin. Interferon gamma (IFNgamma) and interleukin 4 (IL4) were measured in the
      culture supernatants by enzyme linked immunosorbent assay (ELISA). Serum samples
      from 46 patients with Behcet's disease and from 37 healthy subjects were also
      studied for antibody detection. Antibodies to beta-casein, beta-lactoglobulin,
      and chicken egg albumin were determined by ELISA. RESULTS: High IFNgamma but not
      IL4 levels were found in the supernatants of lymphocytes from patients with
      active disease cultured in the presence of cow's milk proteins. Levels were
      comparable with those obtained in cultures stimulated with PHA. A significantly
      higher level of anti-beta-casein and anti-beta-lactoglobulin IgG and IgA
      antibodies was found in patients with active Behcet's disease. No relation was
      found between their occurrence and the age of the patients, the duration of
      disease, or the presence of gastrointestinal abnormalities. Antibodies to chicken
      albumin were detected at low levels and with a prevalence similar to that of
      healthy subjects. CONCLUSION: The results indicate that an active immune response
      occurs in Behcet's disease. This response involves an increased frequency of
      antibodies to cow's milk protein and a strong Th1 polarisation after exposure to
      these antigens. The occurrence of these abnormalities supports a putative role
      for cow's milk proteins immune response in the pathogenesis of Behcet's disease.

PMID- 11959774
TI  - Obstruction of the pulmonary artery by granulomatous vasculitis: a clinical,
      morphological, and immunological analysis.

PMID- 11959775
TI  - Rheumatism in the early 18th century: a doctor's diary.

PMID- 11959776
TI  - Successful use of infliximab in a patient with treatment resistant
      spondyloarthropathy related uveitis.

PMID- 11959777
TI  - Incidence of systemic lupus erythematosus among 255 patients with uveitis of
      unknown origin.

PMID- 11959778
TI  - Raynaud's phenomenon affecting the tongue of a patient with scleroderma.

PMID- 11959779
TI  - T cell response to human HSP60 and yersinia 19 kDa in ankylosing spondylitis and
      rheumatoid arthritis: no evidence for a causal role of these antigens in the
      pathogenesis.

PMID- 11959780
TI  - Kikuchi-Fujimoto disease and peripheral arthritis: a first!

PMID- 11959781
TI  - Guidelines for the treatment of osteoarthritis.

PMID- 11959782
TI  - Rheumatic pneumonia.

PMID- 11959783
TI  - Salmonella arteritis.

PMID- 11959784
TI  - 2-Chloro-N6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate is a
      selective high affinity P2Y1 receptor antagonist: commentary on Boyer et al.

PMID- 11959785
TI  - Bretylium or 6-OHDA-resistant, action potential-evoked Ca2+ transients in
      varicosities of the mouse vas deferens: commentary on Jackson and Cunnane.

PMID- 11959786
TI  - Bretylium or 6-OHDA-resistant, action potential-evoked Ca2+ transients in
      varicosities of the mouse vas deferens.
AB  - Action potential-evoked calcium transients in varicosities in mouse vas deferens
      were monitored using laser scanning confocal microscopy. Their significance was
      examined by comparison with excitatory junction potentials (EJPs) and neurogenic
      contractions, both indirect measurements of transmitter release. Bretylium
      abolished EJPs, as well as the ATP and NA-mediated phases of contraction.
      However, bretylium revealed a prominent late component of contraction that was
      atropine-sensitive. Bretylium abolished calcium transients in 21%, enhanced in
      16% and had no effect in 63% of varicosities examined. Pre-treatment with 6-OHDA
      reduced NA levels to below detectable levels but many strings of varicosities
      still responded to nerve impulses with 'normal' calcium transients. Varicosities
      in which calcium transients were abolished by these agents were sympathetic. The
      identity of those varicosities in which calcium transients were resistant to
      bretylium (sympathetic but no uptake-1 sites, parasympathetic, sensory) remains
      to be established.

PMID- 11959787
TI  - A direct inhibitory action of prostaglandins upon ACTH secretion at the late
      stages of the secretory pathway of AtT-20 cells.
AB  - 1. The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used as a
      model system for the study of the effects of prostaglandins upon the late stages
      of the adrenocorticotrophin (ACTH) secretory pathway. 2. Calcium (1 nM - 100
      microM), guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) (1 - 100 microM) and
      mastoparan (1 and 10 microM) all stimulated ACTH secretion from permeabilized AtT
      20 cells in a concentration-dependent manner. GTP-gamma-S and mastoparan
      stimulated ACTH secretion from permeabilized cells in the absence of calcium. Co
      incubation with prostaglandins E(1) and E(2) (PGE(1), PGE(2)) (10 microM) but not
      prostaglandin F(2 alpha) (PGF(2 alpha)) (10 microM) significantly inhibited
      calcium-, GTP-gamma-S and mastoparan-evoked secretion by 30 - 50%. 3. The effects
      of PGE(1) and PGE(2) upon GTP-gamma-S (100 microM)-, calcium (10 microM)- and
      mastoparan (10 microM)-evoked secretion were concentration-dependent. PGE(1)
      significantly inhibited GTP-gamma-S- and calcium-evoked secretion at
      concentrations of PGE(1) above 1 microM but mastoparan-evoked secretion only at
      the highest concentration of PGE(1) investigated (10 microM). PGE(2) was much
      more potent than PGE(1) and significantly inhibited GTP-gamma-S- and calcium
      evoked secretion at 10 nM and above and mastoparan-evoked secretion above 1
      microM. 4. The inhibitory effects of PGE(1) and PGE(2) upon calcium-, GTP-gamma-S
      and mastoparan-stimulated ACTH secretion from permeabilized cells were pertussis
      toxin (PTX) sensitive. 5. In intact cells PGE(1), PGE(2) and PGF(2 alpha) (1 nM -
      10 microM) acting singly had little or no effect upon ACTH secretion. However,
      only PGE(2) (1 nM - 10 microM) significantly inhibited corticotrophin-releasing
      factor-41 (CRF-41) (100 nM)-evoked secretion in a concentration dependent manner.
      6. The present study finds that prostaglandins of the E series exert an
      inhibitory action, via a pertussis toxin-sensitive GTP-binding (G)-protein, in
      the late stages of the ACTH secretory pathway distal to the G-exocytosis
      (Ge)/calcium point of control.

PMID- 11959788
TI  - Aponecrotic, antiangiogenic and antiproliferative effects of a novel dextran
      derivative on breast cancer growth in vitro and in vivo.
AB  - 1. Since the sodium phenylacetate (NaPa) was reported to enhance the inhibitory
      effect of carboxymethyl benzylamide dextran (CMDB) on the breast cancer growth,
      we performed the esterification of CMDB with NaPa to obtain a new drug carrying
      the characteristics of these two components. A new molecule, phenylacetate
      carboxymethyl benzylamide dextran, was named NaPaC. 2. We investigated in vitro
      and in vivo the effects of NaPaC on MCF-7ras cell growth as well as its apoptotic
      and antiangiogenic effects in comparison to NaPa and CMDB. In addition, we
      assessed in vitro the antiproliferative effects of these drugs on other breast
      cancer cells, including MDA-MB-231, MDA-MB-435 and MCF-7. 3. In vitro, NaPaC
      inhibited MCF-7ras cell proliferation by 40% at concentration lower than that of
      CMDB and NaPa (12 microM vs 73 microM and 10 mM). IC(50)s were 6 and 28 microM
      for NaPaC and CMDB, respectively. The similar results were obtained for three
      other breast cancer cell lines. NaPaC reduced the DNA replication and induced
      cell recruitment in G(0)/G(1) phase more efficiently than its components.
      Moreover, it induced a cell death at concentration 1000-fold lower than NaPa. 4.
      In vivo, CMDB (150 mg kg(-1)) and NaPa (40 mg kg(-1)) inhibited the MCF-7ras
      tumour growth by 37 and 57%, respectively, whereas NaPaC (15 mg kg(-1)) decreased
      tumour growth by 66% without toxicity. 5. NaPa or CMDB reduced the microvessel
      number in tumour by 50% after 7 weeks of treatment. NaPaC had the same effect
      after only 2 weeks. After 7 weeks, it generated a large necrosis area without
      detectable microvessels. In vitro, NaPaC inhibited human endothelial cell
      proliferation more efficiently than CMDB or NaPa. NaPaC interacts with vascular
      endothelial growth factor as observed by affinity electrophoresis. 6. NaPaC acts
      like NaPa and CMDB but in more potent manner than components used separately. Its
      antiproliferative, aponecrotic and anti-angiogenic actions make it a good
      candidate for a new anti-cancer drug.

PMID- 11959789
TI  - Rolipram inhibits leukocyte-endothelial cell interactions in vivo through P- and
      E-selectin downregulation.
AB  - 1. Rolipram, a selective phosphodiesterase (PDE) type 4 inhibitor, was used to
      characterize leukocyte recruitment mechanisms in models of acute and subacute
      inflammation. Intravital microscopy within the rat mesenteric microcirculation
      was employed. 2. Mesentery superfusion with PAF (0.1 microM) induced a
      significant increase in leukocyte rolling flux, adhesion and emigration at 60
      min. Rolipram pretreatment, markedly inhibited these parameters by 100, 95 and
      95% respectively. 3. Similar effects were observed when the mesentery was
      superfused with LPS (1 microg ml(-1)) for the same time period and these
      leukocyte parameters were nearly abrogated by rolipram pretreatment. 4. LPS
      exposure of the mesentery for 4 h caused a greater increase in leukocyte rolling
      flux, adhesion and emigration which were inhibited by rolipram administration by
      51, 71 and 81% respectively. 5. Immunohistochemistry revealed a significant
      increase in P-selectin expression after 60 min superfusion with PAF which was
      attenuated by rolipram. 6. LPS exposure of the mesentery for 4 h caused a
      significant increase in P- and E-selectin, intercellular adhesion molecule-1
      (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. Rolipram
      pretreatment down-regulated both P- and E-selectin expression but had no effect
      on ICAM-1 and VCAM-1 expression. 7. Significant increases in plasma cyclic AMP
      levels were detected at 4.5 h after rolipram administration. 8. In conclusion, we
      have demonstrated that rolipram is a potent in vivo inhibitor of leukocyte
      endothelial cell interactions. The effects observed are mediated through
      endothelial P- and E-selectin downregulation. Therefore, selective PDE-4
      inhibitors may be useful in the control of different inflammatory disorders.

PMID- 11959790
TI  - NCX4016 (NO-aspirin) reduces infarct size and suppresses arrhythmias following
      myocardial ischaemia/reperfusion in pigs.
AB  - 1. The effect of the nitro-derivative of aspirin, NCX4016, was assessed on
      ischaemic ventricular arrhythmias and myocardial infarct size in anaesthetized
      pigs in comparison to native aspirin. 2. Pigs were given aspirin (10 mg kg(-1);
      n=6), low dose NCX4016 (18.4 mg kg(-1); n=6) or high dose NCX4016 (60 mg kg(-1);
      n=7) orally for 5 days prior to coronary occlusion and reperfusion. None of the
      interventions had any effect on baseline haemodynamics prior to coronary
      occlusion in comparison to control pigs (n=9). Aspirin and high dose NCX4016 both
      prevented the generation of thromboxane A(2) from platelets activated ex vivo
      with A23187 (30 microM), whereas all three interventions markedly attenuated
      platelet aggregation in response to collagen in whole blood in comparison to
      controls. 3. None of the drug interventions had any effect on the incidence of
      ventricular fibrillation (VF) during myocardial ischaemia (100% in all groups).
      However, 60 mg kg(-1) NCX4016 significantly attenuated the total number of
      premature ventricular beats (PVB's) (62+/-16 vs 273+/-40 in control pigs; P<0.05)
      during the first 30 min of occlusion. The higher dose of NCX4016 also
      significantly reduced myocardial infarct size (22.6+/-3.7% of area at risk vs
      53.0+/-2.8% of area at risk in control pigs; P<0.05). 4. These results suggest
      that the nitro-derivative of aspirin, NCX4016, is an effective antiplatelet
      agent, which unlike aspirin also reduces the extent of myocardial injury
      following ischaemia and reperfusion.

PMID- 11959791
TI  - Complex regional haemodynamic effects of anandamide in conscious rats.
AB  - 1. Experiments were carried out in conscious, chronically instrumented, male,
      Sprague-Dawley rats to delineate the regional haemodynamic effects of the
      putative endogenous cannabinoid, anandamide, (0.075 - 3 mg kg(-1)), and to
      dissect some of the mechanisms involved. 2. At all doses of anandamide, there was
      a significant, short-lived increase in mean arterial blood pressure associated
      with vasoconstriction in renal, mesenteric and hindquarters vascular beds. 3. The
      higher doses (2.5 and 3 mg kg(-1)), caused an initial, marked bradycardia
      accompanied, in some animals, by a fall in arterial blood pressure which preceded
      the hypertension. In addition, after the higher doses of anandamide, the
      hindquarters vasoconstriction was followed by vasodilatation. 4. Although some of
      the effects described above resembled those of 5-HT (25 microg kg(-1)), the
      bradycardia and hypotensive actions of the latter were abolished by the 5HT(3)
      receptor antagonist, azasetron, whereas those of anandamide were generally
      unaffected. 5. None of the cardiovascular actions of anandamide were influenced
      by the CB(1)-receptor antagonist, AM 251, but its bradycardic effect was
      sensitive to atropine, and its hindquarters vasodilator action was suppressed by
      the beta(2)-adrenoceptor antagonist, ICI 118551. 6. The results differ, in
      several aspects, from those previously reported in anaesthetized animals, and
      underscore the important impact anaesthesia can have on responses to anandamide.

PMID- 11959792
TI  - Inhibition of spontaneous acetylcholine secretion by 2-chloroadenosine as
      revealed by a protein kinase inhibitor at the mouse neuromuscular junction.
AB  - 1. Previous studies have reported discrepancies in the potencies of A(1)
      adenosine receptor agonists at mouse motor nerve terminals. In addition,
      conflicting results on the role of protein kinase A (PKA) in mediating the
      inhibitory effects of A(1) receptor agonists have been published. We thus decided
      to investigate the possibility of endogenous control of adenosine receptor
      sensitivity by protein kinases, using a variety of protein kinase inhibitors in
      conjunction with the adenosine receptor agonist 2-chloroadenosine (CADO). 2.
      CADO, at the concentration employed previously to study spontaneous ACh release
      in the mouse (1 microM), did not inhibit spontaneous ACh release in our
      experiments. However, a higher concentration of CADO (10 microM) produced highly
      statistically-significant reductions in spontaneous ACh release. 3. In the
      presence of the non-selective protein kinase inhibitor, H7 (50 microM), the
      potency of CADO was increased such that 1 microM CADO now reduced spontaneous
      quantal ACh release to approximately 63% of control. 4. Both H7, and the
      selective PKA inhibitor, KT5720 (500 nM) prevented increases in ACh release
      produced by CPT cyclic AMP (250 microM), suggesting these kinase inhibitors were
      blocking PKA. In contrast to H7, however, KT5720, did not reveal an inhibitory
      effect of 1 microM CADO. A number of other non-selective PKA inhibitors also
      failed to increase the potency of CADO. 5. The results suggest that an endogenous
      H7-sensitive process modulates the sensitivity of the mouse A(1) adenosine
      receptor and that the inhibitory effects of CADO are independent of cyclic AMP
      accumulation or PKA inhibition.

PMID- 11959793
TI  - Mouse beta 3a- and beta 3b-adrenoceptors expressed in Chinese hamster ovary cells
      display identical pharmacology but utilize distinct signalling pathways.
AB  - 1. This study characterizes the mouse beta(3a)-adrenoceptor (AR) and the splice
      variant of the beta(3)-AR (beta(3b)-AR) expressed in Chinese hamster ovary cells
      (CHO-K1). 2. Stable clones with high (approximately 1200), medium (approximately
      500) or low receptor expression (approximately 100 fmol mg protein(-1)) were
      determined by saturation binding with [(125)I]-(-)-cyanopindolol. Competition
      binding studies showed no significant differences in affinity of beta-AR ligands
      for either receptor. 3. Several functional responses of each receptor were
      measured, namely extracellular acidification rate (EAR; cytosensor
      microphysiometer), cyclic AMP accumulation, and Erk1/2 phosphorylation. The
      beta(3)-AR agonists BRL37344, CL316243, GR265162X, L755507, SB251023, the non
      conventional partial beta-AR agonist CGP12177 and the beta-AR agonist (-)
      isoprenaline caused concentration-dependent increases in EAR in cells expressing
      either splice variant. CL316243 caused concentration-dependent increases in
      cyclic AMP accumulation and Erk1/2 phosphorylation in cells expressing either
      receptor. 4. PTX treatment increased maximum EAR and cyclic AMP responses to
      CL316243 in cells expressing the beta(3b)-AR but not in cells expressing the
      beta(3a)-AR at all levels of receptor expression. 5. CL316243 increased Erk1/2
      phosphorylation with pEC(50) values and maximum responses that were not
      significantly different in cells expressing either splice variant. Erk1/2
      phosphorylation was insensitive to PTX or H89 (PKA inhibitor) but was inhibited
      by LY294002 (PI3K gamma inhibitor), PP2 (c-Src inhibitor), genistein (tyrosine
      kinase inhibitor) and PD98059 (MEK inhibitor). 6. The adenylate cyclase
      activators forskolin or cholera toxin failed to increase Erk1/2 levels although
      both treatments markedly increased cyclic AMP accumulation in both beta(3a)- or
      beta(3b)-AR transfected cells. 7. These results suggest that in CHO-K1 cells, the
      beta(3b)-AR, can couple to both G(s) and G(i) to stimulate and inhibit cyclic AMP
      production respectively, while the beta(3a)-AR, couples solely to G(s) to
      increase cyclic AMP levels. However, the increase in Erk1/2 phosphorylation
      following receptor activation is not dependent upon coupling of the receptors to
      G(i) or the generation of cyclic AMP.

PMID- 11959795
TI  - Characterization of cocaine and antidepressant-sensitive norepinephrine
      transporters in rat placental trophoblasts.
AB  - 1. This paper reports on a primary cell culture system that predominantly
      expresses native norepinephrine (NE) transporters (NETs), and is amenable to
      biophysical as well as biochemical analyses. 2. Previous research has identified
      human and rat placentas as rich sources of NET. We have exploited this to develop
      primary cultures of rat placental trophoblasts. NE uptake in these cultures is
      about 10 times higher when compared to 5HT uptake. The presence of NET protein is
      revealed by immunoblot analysis, while there is no detectable SERT protein. 3. NE
      transport in rat trophoblasts is sensitive to NET-specific antagonists,
      desipramine (DS) and nisoxetine (NX), but not to the dopamine-transporter (DAT)
      specific antagonist, GBR12909 or to the serotonin (5HT) transporter (SERT)
      specific antagonist paroxetine (PX). Drugs of abuse such as cocaine and
      amphetamine also inhibit NE transport in these cells. Together these results
      suggest that rat placental trophoblasts predominantly express NET over other
      monoamine transporters. 4. Patch-clamp analysis reveals that NETs in intact rat
      trophoblasts are electrogenic. Comparison of NE uptake with NE-induced currents
      suggests that these two modes of transporter activity are differentially
      regulated.

PMID- 11959794
TI  - Regulation of IL-13 synthesis in human lymphocytes: implications for asthma
      therapy.
AB  - 1. IL-13 is an important mediator in inflammatory diseases such as asthma. IL-13
      is mainly produced by T cells. However, signalling pathways leading to induction
      of this cytokine are not well-characterized. We analysed the regulation of IL-13
      in human peripheral blood mononuclear cells and CD4(+) T cells. 2. Cyclosporine
      (CsA) and FK-506 inhibited IL-13 synthesis, when cells were stimulated by
      TPA/ionomycin. However, stimulation by alpha-CD3/alpha-CD28 led to an enhanced IL
      13 synthesis. 3. NF-kappa B inhibitor N-tosyl-L-lysine chloromethylketone (TLCK)
      inhibited IL-13 synthesis more effectively after TPA/ionomycin stimulation. After
      alpha-CD3/alpha-CD28 stimulation, only 300 microM TLCK inhibited IL-13 synthesis.
      Dexamethasone inhibited IL-13 equally effective after alpha-CD3/alpha-CD28 and
      TPA/ionomycin stimulation. 4. p38 MAPK inhibitor SB203580 inhibited IL-13
      synthesis only partially. MEK inhibitor U0126 inhibited TPA/ionomycin induced IL
      13 synthesis very effectively, whereas alpha-CD3/alpha-CD28 stimulated IL-13
      induction was resistant to this drug. 5. These results were confirmed in purified
      CD4(+) T cells. In difference to PBMCs alpha-CD3/alpha-CD28 stimulated IL-13
      synthesis was effectively inhibited by CsA, FK-506 and U0126. 6. Therefore U0126
      was tested in an animal model of allergic asthma. We could demonstrate for the
      first time that inhibition of the MEK - ERK cascade is a therapeutic option for
      asthma. Intraperitoneal administration of 10 mg kg(-1) U0126 reduced lung
      eosinophilia in ovalbumin-challenged Brown Norway rats by 44%. 7. These results
      demonstrate that different signalling pathways are involved in regulating IL-13
      synthesis in primary human T cells. Characterizing highly potent inhibitors of IL
      13 synthesis can be exploited to identify new drugs to treat immunological
      diseases such as asthma.

PMID- 11959796
TI  - Effects of chronic administration of the novel endothelin antagonist J-104132 on
      endothelial dysfunction in streptozotocin-induced diabetic rat.
AB  - 1. The biosynthesis of endothelin-1 is increased in the diabetic state. So this
      peptide may cause diabetic vascular complications. We tested this possibility by
      chronically administering J-104132, a potent orally active mixed antagonist of
      endothelin A and B (ET(A)/ET(B)) receptors to streptozotocin (STZ)-induced
      diabetic rats and focusing on changes in endothelial function. 2. The
      acetylcholine (ACh)-induced endothelium-dependent relaxation was impaired in
      diabetic rats and this impairment was significantly attenuated following chronic
      administration of J-104132 (10 mg kg(-1), p.o., daily for 4 weeks). 3. In an in
      vitro experiment using aortae from diabetic rats, the ACh-induced relaxation was
      not changed by the presence of J-104132 (3 x 10(-9) M). 4. The expression levels
      of the mRNA for endothelial nitric oxide synthase was comparable among aortae
      from the three groups (control, diabetic and chronically J-104132-treated
      diabetic). 5. The amount of superoxide anion was significantly greater in aortae
      from diabetic rats than in controls. Chronic J-104132 treatment significantly
      decreased the level of superoxide anion in diabetic rats. 6. The expression of
      the p22phox mRNA for the NADH/NADPH oxidase subunit was significantly increased
      in STZ-induced diabetic rats and this increase was completely prevented by
      chronic administration of J-104132. 7. These results suggest that in STZ-induced
      diabetic rats, ET-1 may be directly involved in impairing endothelium-dependent
      relaxation via increased superoxide-anion production.

PMID- 11959797
TI  - Direct visualization of ligand-protein interactions using atomic force
      microscopy.
AB  - 1. Streptavidin is a 60-kDa tetramer which binds four molecules of biotin with
      extremely high affinity (K(A) approximately 10(14) M(-1)). We have used atomic
      force microscopy (AFM) to visualize this ligand-protein interaction directly. 2.
      Biotin was tagged with a short (152-basepair; 50-nm) DNA rod and incubated with
      streptavidin. The resulting complexes were then imaged by AFM. The molecular
      volume of streptavidin calculated from the dimensions of the protein particles
      (105+/-3 nm(3)) was in close agreement with the value calculated from its
      molecular mass (114 nm(3)). Biotinylation increased the apparent size of
      streptavidin (to 133+/-2 nm(3)), concomitant with an increase in the thermal
      stability of the tetramer. 3. Images of streptavidin with one to four molecules
      of DNA-biotin bound were obtained. When two ligands were bound, the angle between
      the DNA rods was either acute or obtuse, as expected from the relative
      orientations of the biotin binding sites. The ratio of acute : obtuse angles (1 :
      3) was lower than the expected value (1 : 2), indicating a degree of steric
      hindrance in the binding of the DNA-biotin. The slight under-representation of
      higher occupancy states supported this idea. 4. Streptavidin with a single
      molecule of DNA-biotin bound was used to tag biotinylated beta-galactosidase, a
      model multimeric enzyme. 5. The ability to image directly the binding of a ligand
      to its protein target by AFM provides useful information about the nature of the
      interaction, and about the effect of complex formation on the structure of the
      protein. Furthermore, the use of DNA-biotin/streptavidin tags could potentially
      shed light on the architecture of multi-subunit proteins.

PMID- 11959798
TI  - Activity profile of calpains I and II in chronically infarcted rat myocardium-
      influence of the calpain inhibitor CAL 9961.
AB  - 1. The calpains have been proposed to be activated following cardiac ischaemia
      and to contribute to myocyte damage after myocardial infarction (MI). In this
      study, the activity of calpains I and II in the infarcted and non-infarcted rat
      myocardium and the action of the selective calpain inhibitor, CAL 9961, has been
      investigated. 2. MI was induced by permanent ligation of the left coronary
      artery. One, 3, 7 and 14 days post MI, the enzymes calpain I and II were
      separated from homogenates of the interventricular septum (IS) and left
      ventricular free wall (LVFW) by chromatography on DEAE-Sepharose. The activity of
      the calpains was measured in sham-operated and MI animals chronically treated
      with placebo or CAL 9961 (15 mg kg(-1) d(-1) s.c.) in a synthetic substrate
      assay. Treatment was started 3 days before MI induction. 3. Calpain I activity
      reached highest values in IS 14 days post MI, whereas maximum activity of calpain
      II was measured in LVFW 3 days post MI. In experiments in vitro, CAL 9961
      completely inhibited both calpains. In vivo, chronic treatment of MI animals with
      CAL 9961 partially prevented the increase in calpain I activity in IS and reduced
      calpain II activity in LVFW to sham levels. 4. Our findings demonstrate that
      calpains I and II are activated after MI, however, both enzymes differ in their
      regional and temporal activation within the infarcted myocardium. Chronic
      inhibition of these enzymes with CAL 9961 might limit the calpain-induced
      myocardial damage and preserve cardiac structural integrity post MI.

PMID- 11959799
TI  - Xestospongin C, a novel blocker of IP3 receptor, attenuates the increase in
      cytosolic calcium level and degranulation that is induced by antigen in RBL-2H3
      mast cells.
AB  - 1. We evaluated the role of the cross-linking of Fc epsilon RI-mediated inositol
      1,4,5-triphosphate (IP(3)) in the increase in cytosolic Ca(2+) level
      ([Ca(2+)](i)) using xestospongin C, a selective membrane permeable blocker of
      IP(3) receptor, in RBL-2H3 mast cells. 2. In the cells sensitized with anti
      dinitrophenol (DNP) IgE, DNP-human serum albumin (DNP-HSA) and thapsigargin
      induced degranulation of beta-hexosaminidase and a sustained increase in
      [Ca(2+)](i). Xestospongin C (3 - 10 microM) inhibited both of these changes that
      were induced by DNP-HSA without changing those induced by thapsigargin. 3. In the
      absence of external Ca(2+), DNP-HSA induced a transient increase in [Ca(2+)](i).
      Xestospongin C (3 - 10 microM) inhibited this increase in [Ca(2+)](i). 4. In the
      cells permeabilized with beta-escin, the application of IP(3) decreased Ca(2+) in
      the endoplasmic reticulum (ER) as evaluated by mag-fura-2. Xestospongin C (3 - 10
      microM) inhibited the effect of IP(3). 5. After the depletion of Ca(2+) stores
      due to stimulation with DNP-HSA or thapsigargin, the addition of Ca(2+) induced
      capacitative calcium entry (CCE). Xestospongin C (3 - 10 microM) inhibited the
      DNP-HSA-induced CCE, whereas it did not affect the thapsigargin-induced CCE. 6.
      These results suggest that Fc epsilon RI-mediated generation of IP(3) contributes
      to Ca(2+) release not only in the initial phase but also in the sustained phase
      of the increase in [Ca(2+)](i), resulting in prolonged Ca(2+) depletion in the
      ER. The ER Ca(2+) depletion may subsequently activate CCE to achieve a continuous
      [Ca(2+)](i) increase, which is necessary for degranulation in the RBL-2H3 mast
      cells. Xestospongin C may inhibit Ca(2+) release and consequently may attenuate
      degranulation.

PMID- 11959800
TI  - Stimulation of protein kinase B and p70 S6 kinase by the histamine H1 receptor in
      DDT1MF-2 smooth muscle cells.
AB  - 1. Previous studies have shown that the histamine H(1) receptor activates p42/p44
      mitogen-activated protein kinases (MAPK) in DDT(1)MF-2 smooth muscle cells via a
      phosphatidylinositol 3-kinase (PI-3K)-dependent pathway. In this study the effect
      of histamine H(1) receptor stimulation on protein kinase B (PKB) and p70 S6
      kinase, both of which are downstream targets of PI-3K, has been investigated.
      Increases in PKB and p70 S6 kinase activation were monitored by Western blotting
      using phospho-specific PKB (Ser(473)) and p70 S6 kinase (Thr(421)/Ser(424))
      antibodies. 2. Histamine stimulated time and concentration-dependent increases in
      the phosphorylation of PKB and p70 S6 kinase in DDT(1)MF-2 cells. Both responses
      were completely inhibited by the histamine H(1) receptor antagonist mepyramine
      and following pre-treatment with pertussis toxin, to block G(i)/G(o) protein
      dependent pathways. 3. The PI-3K inhibitors wortmannin (IC(50) 5.9+/-0.5 nM) and
      LY 294002 (IC(50) 6.9+/-0.8 microM) attenuated the increase in PKB
      phosphorylation induced by histamine (100 microM) in a concentration-dependent
      manner. 4. Histamine-induced increases in p70 S6 kinase phosphorylation were
      partially sensitive to rapamycin (20 nM; 68% inhibition) but completely blocked
      by wortmannin (100 nM), LY 294002 (30 microM) and the MAPK kinase inhibitor PD
      98059 (50 microM). 5. In summary, these data demonstrate that the histamine H(1)
      receptor stimulates PKB and p70 S6 kinase phosphorylation in DDT(1)MF-2 smooth
      muscle cells. However, functional studies revealed that histamine does not
      stimulate DDT(1)MF-2 cell proliferation or attenuate staurosporine-induced
      caspase-3 activity. The challenge for future research will be to link the
      stimulation of these kinase pathways with the physiological and
      pathophysiological roles of the histamine H(1) receptor.

PMID- 11959801
TI  - The sleep hormone oleamide modulates inhibitory ionotropic receptors in mammalian
      CNS in vitro.
AB  - 1. We examine the sensitivity of GABA(A) and glycine receptors (same ionotropic
      superfamily) to oleamide. We address subunit-dependence/modulatory mechanisms and
      analogies with depressant drugs. 2. Oleamide modulated human GABA(A) currents
      (alpha(1)beta(2)gamma(2L)) in oocytes (EC(50), 28.94+/-s.e.mean of 1.4 microM;
      Maximum 216%+/-35 of control, n=4). Modulation of human alpha1 glycine homo
      oligomers (significant), was less marked, with a lower EC(50) (P<0.05) than GABA
      receptors (EC(50), 22.12+/-1.4 microM; Maximum 171%+/-30, n=11). 3. Only the
      hypnogenic cis geometric isomer enhanced glycine currents (without altering slope
      or maximal current, it reduced the glycine EC(50) from 322 to 239 microM:
      P<0.001). Modulation was not voltage-dependent or associated with a shift in
      E(r). 4. beta 1 containing GABA(A) receptors (insensitive to many depressant
      drugs) were positively modulated by oleamide. Oleamide efficacy was circa 2x
      greater at alpha(1)beta(1)gamma(2L) than alpha(1)beta(2)gamma(2L) (P=0.007).
      Splice variation in gamma subunits did not alter oleamide sensitivity. 5. cis
      9,10-Octadecenoamide had no effect on the equilibrium binding of [(3)H]-muscimol
      or [(3)H]-EBOB to mouse brain membranes. It does not directly mimic GABA, or
      operate as a neurosteroid-, benzodiazepine- or barbiturate-like modulator of
      GABA(A)-receptors. 6. The transport of [(3)H]-GABA into mouse brain
      synaptoneurosomes was unaffected by high micromolar concentrations of cis-9,10
      octadecenoamide. Oleamide does not enhance GABA-ergic currents or prolong IPSCs
      by inhibiting GABA transport. 7. Oleamide is a non-selective modulator of
      inhibitory ionotropic receptors. The sleep lipid exerts its effects indirectly,
      or at a novel recognition site on the GABA(A) complex.

PMID- 11959802
TI  - The involvement of smooth muscle P2X receptors in the prolonged vasorelaxation
      response to purine nucleotides in the rat mesenteric arterial bed.
AB  - 1. ATP and adenine dinucleotides can elicit three different types of vasomotor
      response in the rat mesenteric arterial bed; vasocontraction, rapid relaxation
      (which may be masked by contraction) and slow and prolonged vasorelaxation.
      Contraction is mediated by smooth muscle P2X receptors and rapid relaxation by
      endothelial P2Y receptors. The mechanism of prolonged relaxation is, however,
      controversial. 2. In the present study, bolus injection of doses of alpha,beta
      methylene ATP (alpha,beta-meATP; 5 pmol - 0.5 micromol; P2X receptor agonist) in
      methoxamine-preconstricted rat isolated mesenteric arterial beds, mimicked the
      action of ATP, causing contraction (R(max) 76+/-9 mmHg) followed by prolonged
      relaxation (78+/-11%; t(1/2) 14.6+/-1.5 min). KCl also elicited a biphasic
      response (R(max) contraction 73+/-8 mmHg; R(max) prolonged relaxation 70+/-6%;
      t(1/2) 7.7+/-1.9 min). 3. P2X receptor desensitization caused by perfusion with
      alpha,beta-meATP (10 microM) abolished contraction and prolonged relaxation to
      doses of alpha,beta-meATP (50 nmol). Rapid relaxation (32+/-7%; t(1/2) 32+/-2 s)
      was revealed, which was abolished by removal of the endothelium using distilled
      water. 4. Sodium deoxycholate treatment blocked contractile and prolonged
      relaxation responses to alpha,beta-meATP, ATP and KCl, whilst distilled water
      treatment had no significant effect on either phase of the biphasic responses. 5.
      These data indicate that smooth muscle P2X receptors are involved in both phases
      of the biphasic response (contraction followed by prolonged relaxation) to purine
      nucleotides in the rat isolated mesenteric arterial bed. Caution should be
      applied when using sodium deoxycholate to remove the endothelium because of
      possible damage caused by the detergent to receptors and/or the vascular smooth
      muscle.

PMID- 11959804
TI  - 2-Chloro N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate is a
      selective high affinity P2Y(1) receptor antagonist.
AB  - 1. We reported previously that bisphosphate derivatives of adenosine are
      antagonists of the P2Y(1) receptor and that modification of the ribose in these
      analogues is tolerated in the P2Y(1) receptor binding pharmacophore. 2. Here we
      delineate the pharmacological activity of one such non-nucleotide molecule, 2
      chloro N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate
      (MRS2279), in which the ribose is replaced by a cyclopentane ring constrained in
      the (N)-conformation by a cyclopropane moiety. 3. MRS2279 antagonized 2MeSADP
      stimulated inositol phosphate formation in turkey erythrocyte membranes with
      competitive kinetics (pK(B)=7.75). High affinity competitive antagonism by
      MRS2279 was also observed at the human P2Y(1) receptor (pK(B)=8.10) stably
      expressed in 1321N1 human astrocytoma cells. Antagonism was specific for the
      P2Y(1) receptor since MRS2279 had no effect on activation of the human P2Y(2),
      P2Y(4), P2Y(6), or P2Y(11) receptors by their cognate agonists. 4. MRS2279 also
      did not block the capacity of ADP to act through the Gi/adenylyl cyclase linked
      P2Y receptor of platelets to inhibit cyclic AMP accumulation. 5. In contrast, the
      P2Y(1) receptor is known to be obligatory in the process of ADP-induced platelet
      aggregation, and MRS2279 competitively inhibited ADP-promoted platelet
      aggregation with an apparent affinity (pK(B)=8.05) similar to that observed at
      the human P2Y(1) receptor heterologously expressed in 1321N1 cells. 6. Taken
      together these results illustrate selective high affinity antagonism of the
      P2Y(1) receptor by a non-nucleotide molecule that should prove useful for
      pharmacological delineation of this receptor in various tissues.

PMID- 11959803
TI  - In vitro and in vivo pharmacology of a structurally novel Na+-H+ exchange
      inhibitor, T-162559.
AB  - 1. We investigated the inhibitory effects of a non-acylguanidine Na(+)-H(+)
      exchange (NHE) inhibitor, T-162559 ((5E,7S)-[7-(5-fluoro-2-methylphenyl)-4-methyl
      7,8-dihydro-5(6H)-quinolinylideneamino] guanidine dimethanesulphonate), on NHE-1,
      and its cardioprotective effect against ischaemia and reperfusion injury in rats
      and rabbits. 2. T-162559 inhibited human platelet NHE-1 in a concentration
      dependent manner, with an IC(50) value of 13+/-3 nmol l(-1), making it 16 and
      three times more potent than cariporide IC(50): 209+/-75 nmol l(-1), P<0.01) and
      eniporide (IC(50): 40+/-11 nmol l(-1), P=0.066), respectively. T-162559 also
      inhibited rat NHE-1 with an IC(50) value of 14+/-2 nmol l(-1), which was five and
      three times lower than that of cariporide (IC(50): 75+/-7 nmol l(-1), P<0.01) and
      eniporide (IC(50): 44+/-2 nmol l(-1), P<0.01), respectively. 3. T-162559
      inhibited, in a concentration-dependent manner, the reduction in cardiac
      contractility, progression of cardiac contracture, and increase in lactate
      dehydrogenase release after global ischaemia and reperfusion in perfused rat
      hearts. The inhibitory effects of T-162559 were observed at a lower concentration
      range (10 - 100 nmol l(-1)) than with cariporide and eniporide. T-162559 did not
      alter basal cardiac contractility or coronary flow after reperfusion, suggesting
      that it exerts direct cardioprotective effects on the heart. 4. Intravenous
      administration of T-162559 (0.03 and 0.1 mg kg(-1)) significantly inhibited the
      progression of myocardial infarction induced by left coronary artery occlusion
      and reperfusion in rabbits; the infarct size normalized by area at risk was 74+/
      6% in the vehicle group, and 47+/-5% and 51+/-7% in the T-162559-0.03 mg kg(-1)
      and T-162559-0.1 mg kg(-1) groups (both P<0.05), respectively. 5. These results
      indicate that the new structural NHE-1 inhibitor T-162559 is more potent than
      cariporide and eniporide and possesses a cardioprotective effect against
      ischaemia and reperfusion injury in rat and rabbit models.

PMID- 11959805
TI  - Generalized loss of inhibitory innervation reverses serotonergic inhibition into
      excitation in a rabbit model of TNBS-colitis.
AB  - 1. Inflammation may affect subpopulations of neurons of the myenteric plexus. 2.
      In the present study the effect of trinitrobenzene sulphonic acid (TNBS) induced
      colitis on nitrergic, purinergic and adrenergic inhibitory neurotransmission was
      studied as well as the consequences of the related changes on the response of 5
      HT agonists using these neurotransmitters to mediate their effect. 3. Strips from
      normal and colitis rabbits (135 mg kg(-1) TNBS) were subjected to electrical
      field stimulation (EFS, 0.3 ms, 6V, 0.5 - 32 Hz, 10 s train). The response was
      measured isometrically in the absence or presence of L-NAME, suramin,
      guanethidine, the 5-HT agonists (5-HT(1/5A/7): 5-carboxamidotryptamine (5-CT), 5
      HT(2): alpha-methyl-5-HT, 5-HT(3): 2-methyl-5-HT, 5-HT(4): 5-methoxytryptamine (5
      MeOT)) or a combination. 4. In normal strips L-NAME (1 - 32 Hz), suramin (0.5 -
      2, 8 Hz) and guanethidine (4, 16, 32 Hz) increased the response to EFS. This
      effect was abolished in inflamed strips and was accompanied by a decrease in nNOS
      expression. 5. In normal strips all 5-HT agonists induced pronounced (5-CT, alpha
      methyl-5-HT) or small (2-methyl-5-HT, 5-MeOT) inhibitory neural responses. In
      inflamed strips this was reversed to cholinergic excitatory responses. 6. The
      effect of inflammation on the 5-HT(4) response was mimicked by preincubation of
      normal strips with L-NAME or suramin. Accordingly, in inflamed strips L-NAME or
      suramin did not affect the excitatory effects of 5-MeOT. 7. TNBS-colitis
      abolishes nitrergic, purinergic and adrenergic neurotransmission. This reverses
      serotonergic inhibition into excitation.

PMID- 11959806
TI  - Second messenger-dependent protein kinases and protein synthesis regulate
      endogenous secretin receptor responsiveness.
AB  - 1. The present study investigated the role of second messenger-dependent protein
      kinase A (PKA) and C (PKC) in the regulation of endogenous secretin receptor
      responsiveness in NG108-15 mouse neuroblastomaxrat glioma hybrid cells. 2. In
      whole cell cyclic AMP accumulation studies, activation of PKC either by phorbol
      12-myristate 13-acetate (PMA) or by purinoceptor stimulation using uridine 5'
      triphosphate (UTP) decreased secretin receptor responsiveness. PKC activation
      also inhibited forskolin-stimulated cyclic AMP accumulation but did not affect
      cyclic AMP responses mediated by the prostanoid-IP receptor agonist iloprost, or
      the A(2) adenosine receptor agonist 5'-(N-ethylcarboxamido) adenosine (NECA). 3.
      In additivity experiments, saturating concentrations of secretin and iloprost
      were found to be additive in terms of cyclic AMP accumulation, whereas saturating
      concentrations of NECA and iloprost together were not. This suggests
      compartmentalization of G(s)-coupling components in NG108-15 cells and possible
      heterologous regulation of secretin receptor responsiveness at the level of
      adenylyl cyclase activation. 4. Cells exposed to the PKA inhibitor H-89,
      exhibited a time-dependent increase in secretin receptor responsiveness compared
      to control cells. This effect was selective since cyclic AMP responses to
      forskolin, iloprost and NECA were not affected by H-89 treatment. Furthermore,
      treatment with the protein synthesis inhibitor cycloheximide produced a time
      dependent increase in secretin receptor responsiveness. 5. Together these results
      indicate that endogenous secretin receptor responsiveness is regulated by PKC,
      PKA and protein neosynthesis in NG108-15 cells.

PMID- 11959807
TI  - Receptor subtypes Y1 and Y5 mediate neuropeptide Y induced feeding in the guinea
      pig.
AB  - 1. Neuropeptide Y (NPY) is one of the most potent stimulants of food intake. It
      has been debated which receptor subtype mediates this response. Initially Y(1)
      was proposed, but later Y(5) was announced as a 'feeding' receptor in rats and
      mice. Very little is known regarding other mammals. The present study attempts to
      characterize the role of NPY in feeding behaviour in the distantly related guinea
      pig. When infused intracerebroventricularly, NPY dose-dependently increased food
      intake. 2. PYY, (Leu(31),Pro(34))NPY and NPY(2 - 36) stimulated feeding, whereas
      NPY(13 - 36) had no effect. These data suggest that either Y(1) or Y(5) receptors
      or both may mediate NPY induced food intake in guinea-pigs. 3. The Y(1) receptor
      antagonists, BIBO 3304 and H 409/22 displayed nanomolar affinity for the Y(1)
      receptor (K(i) values 1.1+/-0.2 nM and 5.6+/-0.9 nM, respectively), but low
      affinity for the Y(2) or Y(5) receptors. When guinea-pigs were pretreated with
      BIBO 3304 and H 409/22, the response to NPY was inhibited. 4. The Y(5)
      antagonist, CGP 71683A had high affinity for the Y(5) receptor (K(i) 1.3+/-0.05
      nM) without having any significant activities at the Y(1) and Y(2) receptors.
      When CGP 71683A was infused into brain ventricles, the feeding response to NPY
      was attenuated. 5. The present study shows that NPY stimulates feeding in guinea
      pigs through Y(1) and Y(5) receptors. As the guinea-pig is very distantly related
      to the rat and mouse, this suggests that both Y(1) and Y(5) receptors may mediate
      NPY-induced hyperphagia also in other orders of mammals.

PMID- 11959808
TI  - Resolution of P-glycoprotein and non-P-glycoprotein effects on drug permeability
      using intestinal tissues from mdr1a (-/-) mice.
AB  - 1. Intestinal xenobiotic transporters are a significant barrier to the absorption
      of many orally administered drugs. P-glycoprotein (PGP) is the best known, but
      several others, including members of the multidrug resistance-associated protein
      (MRP) family, are also expressed. Definitive information on their precise effect
      on intestinal drug permeability is scarce due to a lack of specific inhibitors
      and the difficulty of studying non-PGP activity in the presence of high PGP
      expression. 2. We have investigated the in vitro use of intestinal tissues from
      PGP knockout (mdr1a (-/-)) mice as a tool for dissecting the mechanisms of
      intestinal drug efflux. The permeability characteristics of digoxin (DIG),
      paclitaxel (TAX) and etoposide (ETOP) were measured in ileum from mdr1a (-/-) and
      wild-type (FVB) mice mounted in Ussing chambers. 3. DIG and TAX exhibited marked
      efflux across FVB tissues (B-A : A-B apparent permeability (P(app)) ratio 10 and
      17 respectively) which was absent in mdr1a (-/-) tissues, confirming that PGP is
      the sole route of intestinal efflux for these compounds. The A-B P(app) of both
      compounds was 3 - 5 fold higher in mdr1a (-/-) than in FVB. 4. Polarized
      transport of ETOP in FVB tissues was reduced but not abolished in mdr1a (-/-)
      tissues. Residual ETOP efflux in mdr1a (-/-) tissues was abolished by the MRP
      inhibitor MK571, indicating involvement of both PGP and MRP. 5. MK571 abolished
      calcein efflux in mdr1a (-/-) tissues, while quinidine had no parallel effect in
      FVB tissues, suggesting involvement of MRP but not PGP. 6. Tissues from mdr1a (-/
      ) mice provide a novel approach for investigating the influence of PGP ablation
      on intestinal permeability and for resolving PGP and non-PGP mechanisms that
      modulate drug permeability.

PMID- 11959810
TI  - ARID proteins: a diverse family of DNA binding proteins implicated in the control
      of cell growth, differentiation, and development.
AB  - The ARID family of DNA binding proteins was first recognized approximately 5
      years ago. The founding members, murine Bright and Drosophila dead ringer (Dri),
      were independently cloned on the basis of their ability to bind to AT-rich DNA
      sequences, although neither cDNA encoded a recognizable DNA binding domain.
      Mapping of the respective binding activities revealed a shared but previously
      unrecognized DNA binding domain, the consensus sequence of which extends across
      approximately 100 amino acids. This novel DNA binding domain was designated AT
      rich interactive domain (ARID), based on the behavior of Bright and Dri. The
      consensus sequence occurs in 13 distinct human proteins and in proteins from all
      sequenced eukaryotic organisms. The majority of ARID-containing proteins were not
      cloned in the context of DNA binding activity, however, and their features as DNA
      binding proteins are only beginning to be investigated. The ARID region itself
      shows more diversity in structure and function than the highly conserved
      consensus sequence suggests. The basic structure appears to be a series of six
      alpha-helices separated by beta-strands, loops, or turns, but the structured
      region may extend to an additional helix at either or both ends of the basic six.
      It has also become apparent that the DNA binding activity of ARID-containing
      proteins is not necessarily sequence specific. What is consistent is the evidence
      that family members play vital roles in the regulation of development and/or
      tissue-specific gene expression. Inappropriate expression of ARID proteins is
      also increasingly implicated in human tumorigenesis. This review summarizes
      current knowledge about the structure and function of ARID family members, with a
      particular focus on the human proteins.

PMID- 11959809
TI  - Involvement of purinergic signalling in central mechanisms of body temperature
      regulation in rats.
AB  - 1. P2 purinoreceptors are present in hypothalamic and brainstem nuclei that are
      involved in the regulation of body temperature (T(b)). The role of ATP acting on
      these P2 receptors in thermoregulation was investigated by studying the effects
      of the stable ATP analogue alpha,beta-methyleneATP (alpha,beta-meATP) and P2
      receptor antagonists suramin and pyridoxal-5'-phosphate-6-azophenyl-2',4'
      disulphonic acid (PPADS) on T(b) when injected intracerebroventricularly (i.c.v.)
      via a pre-implanted cannula in conscious rats at various ambient temperatures and
      during lipopolysaccharide (LPS)-induced fever. 2. Depending on ambient
      temperature, alpha,beta-meATP (0.2 micromol, i.c.v.) induced a fall in T(b) (-3.3
      degrees C, P<0.05), no changes in T(b) when compared to pre-injection levels, or
      an increase in T(b) ( approximately 1.0 degrees C, P<0.05) in rats maintained at
      10 degrees C, 25 degrees C and 30 degrees C ambient temperature, respectively. 3.
      Suramin (7 nmol, i.c.v.) induced a lasting (up to 6 h) increase in T(b) (on
      average 1.2 degrees C, P<0.05) in rats kept at 25 degrees C or 30 degrees C, but
      failed to induce any rise in T(b) in rats at 10 degrees C ambient temperature. An
      increase in T(b) was also observed in rats (25 degrees C ambient temperature)
      treated with PPADS (0.2 micromol, i.c.v.). 4. alpha,beta-meATP (0.2 micromol)
      injected i.c.v. or directly into the anterior hypothalamus caused a profound fall
      in T(b) (by 0.9 degrees C and 1.0 degrees C, respectively; P<0.05) during LPS
      (E.coli; 50 microg kg(-1))-induced fever in rats at 25 degrees C ambient
      temperature. Fever was initiated more rapidly in rats treated with suramin (7
      nmol) or PPADS (70 nmol), however its late phase was unaffected. Suramin (7 nmol)
      and PPADS (70 nmol) injected at the time when fever was already developed (2.5 h
      after LPS injections) did not alter febrile T(b). 5. These data indicate that
      purinergic signalling may play a significant role in central mechanisms of T(b)
      regulation at various ambient temperatures and during fever.

PMID- 11959812
TI  - A possible role for insulin-like growth factor-binding protein-3
      autocrine/paracrine loops in controlling hepatocellular carcinoma cell
      proliferation.
AB  - Hepatocellular carcinoma (HCC) is a common malignancy, but treatment outcomes
      have generally remained poor. Specific factors important for the pathogenesis of
      HCC are incompletely understood. Insulin-like growth factors (IGFs) are potent
      autocrine and paracrine mitogens for liver cancer cell proliferation, and their
      bioactivity is reduced by IGF-binding protein 3 (IGFBP-3). In the present study,
      we report that IGFBP-3 protein levels were either undetectable (28.5%) or low
      (71.5%) in human HCC samples examined compared with matched non-neoplastic liver
      tissue by Western blotting. IGFBP-3 was localized to nontumor liver cells by
      immunohistochemistry with greater immunointensity than neoplastic liver cells.
      Levels of type I receptor (IGF-IR) were found to be low in approximately 39% of
      human HCC samples examined compared with matched nontumor tissues. IGF-II was
      overexpressed in 32%, whereas IGF-I expression was decreased in 100% of HCC
      samples. In vitro studies revealed that IGF-I and IGF-II induced HepG2 cell
      proliferation in a dose-dependent manner. Treatment of HepG2 cells with either
      human recombinant IGFBP-3 (hrIGFBP-3) or IGF-II antibody led to a significant
      reduction in cell proliferation. Cotreating these cells with hrIGFBP-3
      significantly attenuated the mitogenic activity of IGF-I. IGF-I-induced
      phosphorylation of IGF-IR beta subunit, IRS-1, mitogen-activated protein kinase,
      Elk-1, and Akt-1 as well as phosphatidylinositol 3'-kinase activity was
      significantly attenuated when hepG2 cells were pretreated with hrIGFBP-3. Our
      data indicate that loss of autocrine/paracrine IGFBP-3 loops may lead to HCC
      tumor growth and suggest that modulating production of the IGFs, IGFBP-3, and IGF
      IR may represent a novel approach in the treatment of HCC.

PMID- 11959813
TI  - Smad3 in the mammary epithelium has a nonredundant role in the induction of
      apoptosis, but not in the regulation of proliferation or differentiation by
      transforming growth factor-beta.
AB  - Transforming growth factor-beta (TGF-beta) regulates proliferation,
      morphogenesis, and functional differentiation in the mammary gland and plays
      complex roles in mammary tumorigenesis. Here we show that the signaling mediators
      Smad1-Smad5 are expressed at all stages of mammary gland development. To begin to
      investigate which Smads mediate which TGF-beta responses, we have analyzed
      mammary gland development in Smad3 null mice. Smad3 null virgin females showed
      delayed mammary gland development. However, this phenotype was secondary to
      ovarian insufficiency because Smad3 null mammary epithelium developed normally in
      hormonally supplemented Smad3 null mice or when transplanted into wild-type
      hosts. Absence of Smad3 had no effect on the ability of TGF-beta to inhibit the
      growth of mammary epithelial cells in culture, and no compensatory changes in
      expression or activation of Smad2 were seen in the Smad3 null epithelium. A small
      but significant decrease in apoptotic cells was seen in involuting glands from
      Smad3 null transplants. The results suggest that epithelial Smad3 is dispensable
      for TGF-beta effects on proliferation and differentiation in the mammary gland,
      but that it contributes in a nonredundant manner to the induction of apoptosis.

PMID- 11959814
TI  - Signaling adaptor protein v-Crk activates Rho and regulates cell motility in 3Y1
      rat fibroblast cell line.
AB  - The adaptor protein Crk has been reported to associate with focal adhesions and
      is thought to be involved in integrin-mediated signaling pathway. However, the
      precise mechanism of Crk-dependent regulation of cytoskeleton still remains under
      investigation. In this study, we have established a v-Crk-inducible cell line in
      rat fibroblasts 3Y1 cells and found that v-Crk activated Rho and induced actin
      stress fiber formation. In addition to the induction of tyrosine-phosphorylation
      of p130(Cas) and paxillin, we demonstrated that v-Crk induced threonine
      phosphorylated bands sized at 72/78 kDa found specifically in 3Y1 cells. Both of
      the inhibitors of Rho and Rho-associated kinase, C3 and Y27632, respectively,
      inhibited these v-Crk-induced biochemical effects. Although v-Crk-induced cells
      exhibited a decrease of cell motility, integrin stimulation recovered the
      suppression of motility. Furthermore, v-Crk enhanced motility in chemotactic
      assay toward fibronectin with additional activation of Rho and the increase of
      levels of CD44 cleavage. These results suggest that v-Crk activated Rho and
      induced actin stress fiber formation and CD44 cleavage leading to the regulation
      of cell motility.

PMID- 11959811
TI  - Differential regulation of a novel variant of the alpha(6) integrin, alpha(6p).
AB  - We have reported previously the existence of an M(r) 70,000 form of the alpha(6)
      integrin called alpha(6p) in a variety of human epithelial cell lines. Four
      different experimental conditions were used to examine the regulation of alpha(6)
      and alpha(6p) integrin. The production of the alpha(6) integrin was decreased by
      45% using a protein translation inhibitor (2.25 microM puromycin), whereas
      production of the alpha(6p) variant was unaffected. The alpha(6p) variant was
      decreased 60% by actin depolymerization (10 microM cytochalasin D) corresponding
      to a decrease in its surface expression, whereas alpha(6) integrin production was
      unaffected. The alpha(6p) variant was resistant to endoglycosidase H treatment,
      whereas the alpha(6) integrin was both sensitive and resistant to endoglycosidase
      H treatment, indicating retention in the endoplasmic reticulum and processing
      through the Golgi apparatus. Additionally, digestion by endoglycosidase F
      demonstrated both alpha(6p) and alpha(6) integrin contained NH(2)-linked
      glycosylations and both shifted M(r) approximately 10,000 on enzymatic digestion.
      Finally, inhibition of serine/threonine phosphatases by either calyculin A (15
      nM) or okadaic acid (62 microM) did not affect alpha(6p), whereas the production
      of alpha(6) integrin was decreased by 50%. These data suggest that the production
      of the alpha(6p) variant is distinct from alpha(6) integrin and may involve a
      post-translational processing event at the cell surface.

PMID- 11959815
TI  - Role of the Src homology 2 domain-containing protein Shb in murine brain
      endothelial cell proliferation and differentiation.
AB  - To study the role of the Src homology 2 (SH2) domain-containing protein Shb in
      angiogenesis, wild-type Shb and SH2 domain-mutated Shb (R522K Shb) were
      overexpressed in murine immortalized brain endothelial cells. The wild-type Shb
      cells exhibited an increased rate of apoptosis on serum withdrawal. Both wild
      type Shb and R522K Shb cells exhibited enhanced spreading concomitant with
      cytoskeletal rearrangements that occurred independently of fibroblast growth
      factor (FGF)-2 stimulation. However, these effects may partly be caused by
      altered regulation of Rac1 and Rap1 activation in the Shb cells. The Shb-induced
      cytoskeletal rearrangements were not dependent on phosphatidylinositol 3' kinase
      activity, but could be reversed by inhibition of Src family kinases. FGF-2 failed
      to further enhance migration of wild-type Shb and R522K Shb cells. The R522K Shb
      cells cultured in collagen gels exhibit diminished tubular morphogenesis when
      treated with FGF-2, implicating the need for a functional Shb molecule in this
      process. These data suggest that Shb plays a role in the proliferation and
      differentiation of endothelial cells and, hence, participates in angiogenesis.

PMID- 11959816
TI  - Caenorhabditis elegans PlexinA, PLX-1, interacts with transmembrane semaphorins
      and regulates epidermal morphogenesis.
AB  - The plexin family transmembrane proteins are putative receptors for semaphorins,
      which are implicated in the morphogenesis of animal embryos, including axonal
      guidance. We have generated and characterized putative null mutants of the C.
      elegans plexinA gene, plx-1. plx-1 mutants exhibited morphological defects:
      displacement of ray 1 and discontinuous alae. The epidermal precursors for the
      affected organs were aberrantly arranged in the mutants, and a plx-1::gfp
      transgene was expressed in these epidermal precursor cells as they underwent
      dynamic morphological changes. Suppression of C. elegans transmembrane
      semaphorins, Ce-Sema-1a and Ce-Sema-1b, by RNA interference caused a displacement
      of ray 1 similar to that of plx-1 mutants, whereas mutants for the Ce-Sema-2a/mab
      20 gene, which encodes a secreted-type semaphorin, exhibited phenotypes distinct
      from those of plx-1 mutants. A heterologous expression system showed that Ce-Sema
      1a, but not Ce-Sema-2a, physically bound to PLX-1. Our results indicate that PLX
      1 functions as a receptor for transmembrane-type semaphorins, and, though Ce-Sema
      2a and PLX-1 both play roles in the regulation of cellular morphology during
      epidermal morphogenesis, they function rather independently.

PMID- 11959817
TI  - Semaphorin 1a and semaphorin 1b are required for correct epidermal cell
      positioning and adhesion during morphogenesis in C. elegans.
AB  - The semaphorin family comprises secreted and transmembrane proteins involved in
      axon guidance and cell migration. We have isolated and characterized deletion
      mutants of C. elegans semaphorin 1a (Ce-sema-1a or smp-1) and semaphorin 1b (Ce
      sema-1b or smp-2) genes. Both mutants exhibit defects in epidermal functions. For
      example, the R1.a-derived ray precursor cells frequently fail to change
      anterior/posterior positions completely relative to their sister tail lateral
      epidermal precursor cell R1.p, causing ray 1 to be formed anterior to its normal
      position next to ray 2. The ray cells, which normally separate from the lateral
      tail seam cell (SET) at the end of L4 stage, remains connected to the SET cell
      even in adult mutant males. The ray 1 defects are partially penetrant in each
      single Ce-sema-1 mutant at 20 degrees C, but are greatly enhanced in Ce-sema-1
      double mutants, suggesting that Ce-Sema-1a and Ce-Sema-1b function in parallel to
      regulate ray 1 position. Both mutants also have defects in other aspects of
      epidermal functions, including head and tail epidermal morphogenesis and touch
      cell axon migration, whereas, smp-1 mutants alone have defects in defecation and
      brood size. A feature of smp-1 mutants that is shared with mutants of mab-20
      (which encodes Sema-2a) is the abnormal perdurance of contacts between epidermal
      cells.

PMID- 11959818
TI  - Regulation of APETALA3 floral homeotic gene expression by meristem identity
      genes.
AB  - The Arabidopsis APETALA3 (AP3) floral homeotic gene is required for specifying
      petal and stamen identities, and is expressed in a spatially limited domain of
      cells in the floral meristem that will give rise to these organs. Here we show
      that the floral meristem identity genes LEAFY (LFY) and APETALA1 (AP1) are
      required for the activation of AP3. The LFY transcription factor binds to a
      sequence, with dyad symmetry, that lies within a region of the AP3 promoter
      required for early expression of AP3. Mutation of this region abolishes LFY
      binding in vitro and in yeast one hybrid assays, but has no obvious effect on AP3
      expression in planta. Experiments using a steroid-inducible form of LFY show
      that, in contrast to its direct transcriptional activation of other floral
      homeotic genes, LFY acts in both a direct and an indirect manner to regulate AP3
      expression. This LFY-induced expression of AP3 depends in part on the function of
      the APETALA1 (AP1) floral homeotic gene, since mutations in AP1 reduce LFY
      dependent induction of AP3 expression. LFY therefore appears to act through
      several pathways, one of which is dependent on AP1 activity, to regulate AP3
      expression.

PMID- 11959819
TI  - A mitogen gradient of dorsal midline Wnts organizes growth in the CNS.
AB  - Cell cycle progression and exit must be precisely patterned during development to
      generate tissues of the correct size, shape and symmetry. Here we present
      evidence that dorsal-ventral growth of the developing spinal cord is regulated by
      a Wnt mitogen gradient. Wnt signaling through the beta-catenin/TCF pathway
      positively regulates cell cycle progression and negatively regulates cell cycle
      exit of spinal neural precursors in part through transcriptional regulation of
      cyclin D1 and cyclin D2. Wnts expressed at the dorsal midline of the spinal cord,
      Wnt1 and Wnt3a, have mitogenic activity while more broadly expressed Wnts do not.
      We present several lines of evidence suggesting that dorsal midline Wnts form a
      dorsal to ventral concentration gradient. A growth gradient that correlates with
      the predicted gradient of mitogenic Wnts emerges as the neural tube grows with
      the proliferation rate highest dorsally and the differentiation rate highest
      ventrally. These data are rationalized in a 'mitogen gradient model' that
      explains how proliferation and differentiation can be patterned across a growing
      field of cells. Computer modeling demonstrates this model is a robust and self
      regulating mechanism for patterning cell cycle regulation in a growing tissue.
      Supplemental data available on-line

PMID- 11959820
TI  - Fgf3 and Fgf8 are required together for formation of the otic placode and
      vesicle.
AB  - Fgf3 has long been implicated in otic placode induction and early development of
      the otocyst; however, the results of experiments in mouse and chick embryos to
      determine its function have proved to be conflicting. In this study, we
      determined fgf3 expression in relation to otic development in the zebrafish and
      used antisense morpholino oligonucleotides to inhibit Fgf3 translation.
      Successful knockdown of Fgf3 protein was demonstrated and this resulted in a
      reduction of otocyst size together with reduction in expression of early markers
      of the otic placode. fgf3 is co-expressed with fgf8 in the hindbrain prior to
      otic induction and, strikingly, when Fgf3 morpholinos were co-injected together
      with Fgf8 morpholinos, a significant number of embryos failed to form otocysts.
      These effects were made manifest at early stages of otic development by an
      absence of early placode markers (pax2.1 and dlx3) but were not accompanied by
      effects on cell division or death. The temporal requirement for Fgf signalling
      was established as being between 60% epiboly and tailbud stages using the Fgf
      receptor inhibitor SU5402. However, the earliest molecular event in induction of
      the otic territory, pax8 expression, did not require Fgf signalling, indicating
      an inductive event upstream of signalling by Fgf3 and Fgf8. We propose that Fgf3
      and Fgf8 are required together for formation of the otic placode and act during
      the earliest stages of its induction.

PMID- 11959821
TI  - Heparan sulphate proteoglycans and spinal neurulation in the mouse embryo.
AB  - Heparan sulphate proteoglycans have been implicated in the binding and
      presentation of several growth factors to their receptors, thereby regulating
      cellular growth and differentiation. To investigate the role of heparan sulphate
      proteoglycans in mouse spinal neurulation, we administered chlorate, a
      competitive inhibitor of glycosaminoglycan sulphation, to cultured E8.5 embryos.
      Treated embryos exhibit accelerated posterior neuropore closure, accompanied by
      suppression of neuroepithelial bending at the median hinge point and accentuated
      bending at the paired dorsolateral hinge points of the posterior neuropore. These
      effects appear specific, as they can be prevented by addition of heparan sulphate
      to the culture medium, whereas heparitinase-treated heparan sulphate and
      chondroitin sulphate are ineffective. Both N- and O-sulphate groups appear to be
      necessary for the action of heparan sulphate. In situ hybridisation analysis
      demonstrates a normal distribution of sonic hedgehog mRNA in chlorate-treated
      embryos. By contrast, patched 1 transcripts are abnormally abundant in the
      notochord, and diminished in the overlying neuroepithelium, suggesting that sonic
      hedgehog signalling from the notochord may be perturbed by inhibition of heparan
      sulphation. Together, these results demonstrate a regulatory role for heparan
      sulphate in mouse spinal neurulation.

PMID- 11959822
TI  - Inductive patterning of the embryonic brain in Drosophila.
AB  - In vertebrates (deuterostomes), brain patterning depends on signals from adjacent
      tissues. For example, holoprosencephaly, the most common brain anomaly in humans,
      results from defects in signaling between the embryonic prechordal plate
      (consisting of the dorsal foregut endoderm and mesoderm) and the brain. I have
      examined whether a similar mechanism of brain development occurs in the
      protostome Drosophila, and find that the foregut and mesoderm act to pattern the
      fly embryonic brain. When the foregut and mesoderm of Drosophila are ablated,
      brain patterning is disrupted. The loss of Hedgehog expressed in the foregut
      appears to mediate this effect, as it does in vertebrates. One mechanism whereby
      these defects occur is a disruption of normal apoptosis in the brain. These data
      argue that the last common ancestor of protostomes and deuterostomes had a
      prototype of the brains present in modern animals, and also suggest that the
      foregut and mesoderm contributed to the patterning of this 'proto-brain'. They
      also argue that the foreguts of protostomes and deuterostomes, which have
      traditionally been assigned to different germ layers, are actually homologous.

PMID- 11959823
TI  - A new role for Mos in Xenopus oocyte maturation: targeting Myt1 independently of
      MAPK.
AB  - The resumption of meiosis in Xenopus arrested oocytes is triggered by
      progesterone, which leads to polyadenylation and translation of Mos mRNA, then
      activation of MAPK pathway. While Mos protein kinase has been reported to be
      essential for re-entry into meiosis in Xenopus, arrested oocytes can undergo
      germinal vesicle breakdown (GVBD) independently of MAPK activation, leading us to
      question what the Mos target might be if Mos is still required. We now
      demonstrate that Mos is indeed necessary, although is independent of the MAPK
      cascade, for conversion of inactive pre-MPF into active MPF. We have found that
      Myt1 is likely to be the Mos target in this process, as Mos interacts with Myt1
      in oocyte extracts and Mos triggers Myt1 phosphorylation on some sites in vivo,
      even in the absence of MAPK activation. We propose that Mos is involved, not only
      in the MAPK cascade pathway, but also in a mechanism that directly activates MPF
      in Xenopus oocytes.

PMID- 11959824
TI  - The C. elegans LAR-like receptor tyrosine phosphatase PTP-3 and the VAB-1 Eph
      receptor tyrosine kinase have partly redundant functions in morphogenesis.
AB  - Receptor-like protein-tyrosine phosphatases (RPTPs) form a diverse family of cell
      surface molecules whose functions remain poorly understood. The LAR subfamily of
      RPTPs has been implicated in axon guidance and neural development. Here we report
      the molecular and genetic analysis of the C. elegans LAR subfamily member PTP-3.
      PTP-3 isoforms are expressed in many tissues in early embryogenesis, and later
      become localized to neuronal processes and to epithelial adherens junctions. Loss
      of function in ptp-3 causes low-penetrance defects in gastrulation and epidermal
      development similar to those of VAB-1 Eph receptor tyrosine kinase mutants. Loss
      of function in ptp-3 synergistically enhances phenotypes of mutations in the C.
      elegans Eph receptor VAB-1 and a subset of its ephrin ligands, but does not show
      specific interactions with several other RTKs or morphogenetic mutants. The
      genetic interaction of vab-1 and ptp-3 suggests that LAR-like RPTPs and Eph
      receptors have related and partly redundant functions in C. elegans
      morphogenesis.

PMID- 11959825
TI  - Organ-specific cell division abnormalities caused by mutation in a general cell
      cycle regulator in C. elegans.
AB  - The precise control of cell division during development is pivotal for
      morphogenesis and the correct formation of tissues and organs. One important gene
      family involved in such control is the p21/p27/p57 class of negative cell cycle
      regulators. Loss of function of the C. elegans p27 homolog, cki-1, causes extra
      cell divisions in numerous tissues including the hypodermis, the vulva, and the
      intestine. We have sought to better understand how cell divisions are controlled
      upstream or in parallel to cki-1 in specific organs during C. elegans
      development. By taking advantage of the invariant cell lineage of C. elegans, we
      used an intestinal-specific GFP reporter in a screen to identify mutants that
      undergo cell division abnormalities in the intestinal lineage. We have isolated a
      mutant with twice the wild-type complement of intestinal cells, all of which
      arise during mid-embryogenesis. This mutant, called rr31, is a fully dominant,
      maternal-effect, gain-of-function mutation in the cdc-25.1 cell cycle phosphatase
      that sensitizes the intestinal lineage to an extra cell division. We showed that
      cdc-25.1 acts at the G1/S transition, as ectopic expression of CDC-25.1 caused
      entry into S phase in intestinal cells. In addition, we showed that the cdc
      25.1(gf) requires cyclin E. The extra cell division defect was shown to be
      restricted to the E lineage and the E fate is necessary and sufficient to
      sensitize cells to this mutation.

PMID- 11959826
TI  - A changing morphogen gradient is interpreted by continuous transduction flow.
AB  - In vertebrate development, most signalling factors behave as morphogens,
      eliciting divergent cell fates according to their concentration. We ask how cells
      interpret morphogen concentration as it changes during the establishment of a
      gradient. Using dissociated blastula cells of Xenopus exposed to activin for only
      10 minutes, we have followed the phosphorylation of tagged Smad2, the principal
      activin transducer, from a cytoplasmic pool to the nucleus in real time. We show
      that a changing concentration of extracellular activin is rapidly and
      continuously transduced to provide a corresponding nuclear concentration of
      Smad2, even though gene response may be delayed for several hours. Nuclear Smad2
      concentration changes up as the extracellular concentration of activin increases.
      We conclude that cells interpret a changing extracellular concentration by
      maintaining a continuous flow of activated transducer from a large cytoplasmic
      pool to the nucleus where it is degraded. The volume of this flow determines the
      steady state concentration of Smad2 in the nucleus and this is used by cells to
      interpret extracellular morphogen concentration.

PMID- 11959827
TI  - Cdx1 and Cdx2 have overlapping functions in anteroposterior patterning and
      posterior axis elongation.
AB  - Mouse Cdx and Hox genes presumably evolved from genes on a common ancestor
      cluster involved in anteroposterior patterning. Drosophila caudal (cad) is
      involved in specifying the posterior end of the early embryo, and is essential
      for patterning tissues derived from the most caudal segment, the analia. Two of
      the three mouse Cdx paralogues, Cdx 1 and Cdx2, are expressed early in a Hox-like
      manner in the three germ layers. In the nascent paraxial mesoderm, both genes are
      expressed in cells contributing first to the most rostral, and then to
      progressively more caudal parts of the vertebral column. Later, expression
      regresses from the anterior sclerotomes, and is only maintained for Cdx1 in the
      dorsal part of the somites, and for both genes in the tail bud. Cdx1 null mutants
      show anterior homeosis of upper cervical and thoracic vertebrae. Cdx2-null
      embryos die before gastrulation, and Cdx2 heterozygotes display anterior
      transformations of lower cervical and thoracic vertebrae. We have analysed the
      genetic interactions between Cdx1 and Cdx2 in compound mutants. Combining mutant
      alleles for both genes gives rise to anterior homeotic transformations along a
      more extensive length of the vertebral column than do single mutations. The most
      severely affected Cdx1 null/Cdx2 heterozygous mice display a posterior shift of
      their cranio-cervical, cervico-thoracic, thoraco-lumbar, lumbo-sacral and sacro
      caudal transitions. The effects of the mutations in Cdx1 and Cdx2 were co
      operative in severity, and a more extensive posterior shift of the expression of
      three Hox genes was observed in double mutants. The alteration in Hox expression
      boundaries occurred early. We conclude that both Cdx genes cooperate at early
      stages in instructing the vertebral progenitors all along the axis, at least in
      part by setting the rostral expression boundaries of Hox genes. In addition, Cdx
      mutants transiently exhibit alterations in the extent of Hox expression domains
      in the spinal cord, reminding of the strong effects of overexpressing Cdx genes
      on Hox gene expression in the neurectoderm. Phenotypical alterations in the
      peripheral nervous system were observed at mid-gestation stages. Strikingly, the
      altered phenotype at caudal levels included a posterior truncation of the tail,
      mildly affecting Cdx2 heterozygotes, but more severely affecting Cdx1/Cdx2 double
      heterozygotes and Cdx1 null/Cdx2 heterozygotes. Mutations in Cdx1 and Cdx2
      therefore also interfere with axis elongation in a cooperative way. The function
      of Cdx genes in morphogenetic processes during gastrulation and tail bud
      extension, and their relationship with the Hox genes are discussed in the light
      of available data in Amphioxus, C. elegans, Drosophila and mice.

PMID- 11959828
TI  - Hes6 regulates myogenic differentiation.
AB  - Hes6 is a basic helix-loop-helix transcription factor homologous to Drosophila
      Enhancer of Split (EoS) proteins. It is known to promote neural differentiation
      and to bind to Hes1, a related protein that is part of the Notch signalling
      pathway, affecting Hes1-regulated transcription. We show that Hes6 is expressed
      in the murine embryonic myotome and is induced on C2C12 myoblast differentiation
      in vitro. Hes6 binds DNA containing the Enhancer of Split E box (ESE) motif, the
      preferred binding site of Drosophila EoS proteins, and represses transcription of
      an ESE box reporter. When overexpressed in C2C12 cells, Hes6 impairs normal
      differentiation, causing a decrease in the induction of the cyclin-dependent
      kinase inhibitor, p21(Cip1), and an increase in the number of cells that can be
      recruited back into the cell cycle after differentiation in culture. In Xenopus
      embryos, Hes6 is co-expressed with MyoD in early myogenic development.
      Microinjection of Hes6 RNA in vivo in Xenopus embryos results in an expansion of
      the myotome, but suppression of terminal muscle differentiation and disruption of
      somite formation at the tailbud stage. Analysis of Hes6 mutants indicates that
      the DNA-binding activity of Hes6 is not essential for its myogenic phenotype, but
      that protein-protein interactions are. Thus, we demonstrate a novel role for Hes6
      in multiple stages of muscle formation.

PMID- 11959829
TI  - Mosaic analyses reveal the function of Drosophila Ras in embryonic dorsoventral
      patterning and dorsal follicle cell morphogenesis.
AB  - In Drosophila melanogaster, the Ras signal transduction pathway is the primary
      effector of receptor tyrosine kinases, which govern diverse developmental
      programs. During oogenesis, epidermal growth factor receptor signaling through
      the Ras pathway patterns the somatic follicular epithelium, establishing the
      dorsoventral asymmetry of eggshell and embryo. Analysis of follicle cell clones
      homozygous for a null allele of Ras demonstrates that Ras is required cell
      autonomously to repress pipe transcription, the critical first step in embryonic
      dorsoventral patterning. The effects of aberrant pipe expression in Ras mosaic
      egg chambers can be ameliorated, however, by post-pipe patterning events, which
      salvage normal dorsoventral polarity in most embryos derived from egg chambers
      with dorsal Ras clones. The patterned follicular epithelium also determines the
      final shape of the eggshell, including the dorsal respiratory appendages, which
      are formed by the migration of two dorsolateral follicle cell populations.
      Confocal analyses of mosaic egg chambers demonstrate that Ras is required both
      cell- and non cell-autonomously for morphogenetic behaviors characteristic of
      dorsal follicle cell migration, and reveal a novel, Ras-dependent pattern of
      basal E-cadherin localization in dorsal midline follicle cells.

PMID- 11959830
TI  - Cerebellar proteoglycans regulate sonic hedgehog responses during development.
AB  - Sonic hedgehog promotes proliferation of developing cerebellar granule cells. As
      sonic hedgehog is expressed in the cerebellum throughout life it is not clear why
      proliferation occurs only in the early postnatal period and only in the external
      granule cell layer. We asked whether heparan sulfate proteoglycans might regulate
      sonic hedgehog-induced proliferation and thereby contribute to the specialized
      proliferative environment of the external granule cell layer. We identified a
      conserved sequence within sonic hedgehog that is essential for binding to heparan
      sulfate proteoglycans, but not for binding to the receptor patched. Sonic
      hedgehog interactions with heparan sulfate proteoglycans promote maximal
      proliferation of postnatal day 6 granule cells. By contrast, proliferation of
      less mature granule cells is not affected by sonic hedgehog-proteoglycan
      interactions. The importance of proteoglycans for proliferation increases during
      development in parallel with increasing expression of the glycosyltransferase
      genes, exostosin 1 and exostosin 2. These data suggest that heparan sulfate
      proteoglycans, synthesized by exostosins, may be critical determinants of granule
      cell proliferation.

PMID- 11959831
TI  - GATA6 regulates differentiation of distal lung epithelium.
AB  - GATA6 is a member of the GATA family of zinc-finger transcriptional regulators
      and is the only known GATA factor expressed in the distal epithelium of the lung
      during development. To define the role that GATA6 plays during lung epithelial
      cell development, we expressed a GATA6-Engrailed dominant-negative fusion protein
      in the distal lung epithelium of transgenic mice. Transgenic embryos lacked
      detectable alveolar epithelial type 1 cells in the distal airway epithelium.
      These embryos also exhibited increased Foxp2 gene expression, suggesting a
      disruption in late alveolar epithelial differentiation. Alveolar epithelial type
      2 cells, which are progenitors of alveolar epithelial type 1 cells, were
      correctly specified as shown by normal thyroid transcription factor 1 and
      surfactant protein A gene expression. However, attenuated endogenous surfactant
      protein C expression indicated that alveolar epithelial type 2 cell
      differentiation was perturbed in transgenic embryos. The number of proximal
      airway tubules is also reduced in these embryos, suggesting a role for GATA6 in
      regulating distal-proximal airway development. Finally, a functional role for
      GATA factor function in alveolar epithelial type 1 cell gene regulation is
      supported by the ability of GATA6 to trans-activate the mouse aquaporin-5
      promoter. Together, these data implicate GATA6 as an important regulator of
      distal epithelial cell differentiation and proximal airway development in the
      mouse.

PMID- 11959832
TI  - Control of photoreceptor cell morphology, planar polarity and epithelial
      integrity during Drosophila eye development.
AB  - We report that the hindsight (hnt) gene, which encodes a nuclear zinc-finger
      protein, regulates cell morphology, cell fate specification, planar cell polarity
      and epithelial integrity during Drosophila retinal development. In the third
      instar larval eye imaginal disc, HNT protein expression begins in the
      morphogenetic furrow and is refined to cells in the developing photoreceptor cell
      clusters just before their determination as neurons. In hnt mutant larval eye
      tissue, furrow markers persist abnormally posterior to the furrow, there is a
      delay in specification of preclusters as cells exit the furrow, there are
      morphological defects in the preclusters and recruitment of cells into specific R
      cell fates often does not occur. Additionally, genetically mosaic ommatidia with
      one or more hnt mutant outer photoreceptor cells, have planar polarity defects
      that include achirality, reversed chirality and misrotation. Mutants in the JNK
      pathway act as dominant suppressors of the hnt planar polarity phenotype,
      suggesting that HNT functions to downregulate JUN kinase (JNK) signaling during
      the establishment of ommatidial planar polarity. HNT expression continues in the
      photoreceptor cells of the pupal retina. When an ommatidium contains four or more
      hnt mutant photoreceptor cells, both genetically mutant and genetically wild-type
      photoreceptor cells fall out of the retinal epithelium, indicating a role for HNT
      in maintenance of epithelial integrity. In the late pupal stages, HNT regulates
      the morphogenesis of rhabdomeres within individual photoreceptor cells and the
      separation of the rhabdomeres of adjacent photoreceptor cells. Apical F-actin is
      depleted in hnt mutant photoreceptor cells before the observed defects in
      cellular morphogenesis and epithelial integrity. The analyses presented here,
      together with our previous studies in the embryonic amnioserosa and tracheal
      system, show that HNT has a general role in regulation of the F-actin-based
      cytoskeleton, JNK signaling, cell morphology and epithelial integrity during
      development.

PMID- 11959833
TI  - Broad specifies pupal development and mediates the 'status quo' action of
      juvenile hormone on the pupal-adult transformation in Drosophila and Manduca.
AB  - The understanding of the molecular basis of the endocrine control of insect
      metamorphosis has been hampered by the profound differences in responses of the
      Lepidoptera and the Diptera to juvenile hormone (JH). In both Manduca and
      Drosophila, the broad (br) gene is expressed in the epidermis during the
      formation of the pupa, but not during adult differentiation. Misexpression of BR
      Z1 during either a larval or an adult molt of Drosophila suppressed stage
      specific cuticle genes and activated pupal cuticle genes, showing that br is a
      major specifier of the pupal stage. Treatment with a JH mimic at the onset of the
      adult molt causes br re-expression and the formation of a second pupal cuticle in
      Manduca, but only in the abdomen of Drosophila. Expression of the BR isoforms
      during adult development of Drosophila suppressed bristle and hair formation when
      induced early or redirected cuticle production toward the pupal program when
      induced late. Expression of BR-Z1 at both of these times mimicked the effect of
      JH application but, unlike JH, it caused production of a new pupal cuticle on the
      head and thorax as well as on the abdomen. Consequently, the 'status quo' action
      of JH on the pupal-adult transformation is mediated by the JH-induced re
      expression of BR.

PMID- 11959835
TI  - Exogenous growth factors induce the production of ganglion cells at the retinal
      margin.
AB  - Neural progenitors at the retinal margin of the post-hatch chicken normally
      produce amacrine and bipolar cells, but not photoreceptor or ganglion cells. The
      purpose of this study was to test whether exogenous growth factors influence the
      types of cells produced by progenitors at the retinal margin. We injected
      insulin, FGF2 or a combination of insulin and FGF2 into the vitreous chamber of
      post-hatch chickens. To assay for growth factor-induced changes at the retinal
      margin, we used in situ hybridization and immunocytochemistry on cryosections.
      One day after the final injection, we found that insulin alone stimulated the
      addition of cells to the retinal margin, but this was not further increased when
      FGF2 was applied with insulin. Insulin alone increased the number of cells in the
      progenitor zone that expressed neurofilament, and this was further increased when
      FGF2 was applied with insulin. These neurofilament-expressing cells in the
      progenitor zone included differentiating neurons that expressed Islet1 or Hu.
      Four days after the final dose of growth factor, we found that the production of
      ganglion cells was induced by co-injection of insulin and FGF2, but not by either
      insulin or FGF2 alone. We conclude that the types of cells produced by
      progenitors at the retinal margin can be altered by exogenous growth factors and
      that normally the microenvironment imposes limitations on the types of neurons
      produced.

PMID- 11959834
TI  - Novel retinoic acid generating activities in the neural tube and heart identified
      by conditional rescue of Raldh2 null mutant mice.
AB  - Retinoid control of vertebrate development depends upon tissue-specific
      metabolism of retinol to retinoic acid (RA). The RA biosynthetic enzyme RALDH2
      catalyzes much, but not all, RA production in mouse embryos, as revealed here
      with Raldh2 null mutants carrying an RA-responsive transgene. Targeted disruption
      of Raldh2 arrests development at midgestation and eliminates all RA synthesis
      except that associated with Raldh3 expression in the surface ectoderm of the eye
      field. Conditional rescue of Raldh2(-/-) embryos by limited maternal RA
      administration allows development to proceed and results in the establishment of
      additional sites of RA synthesis linked to Raldh1 expression in the dorsal retina
      and to Raldh3 expression in the ventral retina, olfactory pit and urinary tract.
      Unexpectedly, conditionally rescued Raldh2(-/-) embryos also possess novel sites
      of RA synthesis in the neural tube and heart that do not correspond to expression
      of Raldh1-3. RA synthesis in the mutant neural tube was localized in the spinal
      cord, posterior hindbrain and portions of the midbrain and forebrain, whereas
      activity in the mutant heart was localized in the conotruncus and sinus venosa.
      In the posterior hindbrain, this novel RA-generating activity was expressed
      during establishment of rhombomeric boundaries. In the spinal cord, the novel
      activity was localized in the floorplate plus in the intermediate region where
      retinoid-dependent interneurons develop. These novel RA-generating activities in
      the neural tube and heart fill gaps in our knowledge of how RA is generated
      spatiotemporally and may, along with Raldh1 and Raldh3, contribute to rescue of
      Raldh2(-/-) embryos by producing RA locally.

PMID- 11959836
TI  - A complex syndrome of left-right axis, central nervous system and axial skeleton
      defects in Zic3 mutant mice.
AB  - X-linked heterotaxy (HTX1) is a rare developmental disorder characterized by
      disturbances in embryonic laterality and other midline developmental field
      defects. HTX1 results from mutations in ZIC3, a member of the GLI transcription
      factor superfamily. A targeted deletion of the murine Zic3 locus has been created
      to investigate its function and interactions with other molecular components of
      the left-right axis pathway. Embryonic lethality is seen in approximately 50% of
      null mice with an additional 30% lethality in the perinatal period. Null embryos
      have defects in turning, cardiac development and neural tube closure.
      Malformations in live born null mice include complex congenital heart defects,
      pulmonary reversal or isomerism, CNS defects and vertebral/rib anomalies.
      Investigation of nodal expression in Zic3-deficient mice indicates that, although
      nodal is initially expressed symmetrically in the node, there is failure to
      maintain expression and to shift to asymmetric expression. Subsequent nodal and
      Pitx2 expression in the lateral plate mesoderm in these mice is randomized,
      indicating that Zic3 acts upstream of these genes in the determination of left
      right asymmetry. The phenotype of these mice correctly models the defects found
      in human HTX1 and indicates an important role for Zic3 in both left-right and
      axial patterning.

PMID- 11959837
TI  - A crucial role of beta 1 integrins for keratinocyte migration in vitro and during
      cutaneous wound repair.
AB  - Integrins are ubiquitous transmembrane receptors that play crucial roles in cell
      cell and cell-matrix interactions. In this study, we have determined the effects
      of the loss of beta 1 integrins in keratinocytes in vitro and during cutaneous
      wound repair. Flow cytometry of cultured beta 1-deficient keratinocytes confirmed
      the absence of beta 1 integrins and showed downregulation of alpha 6 beta 4 but
      not of alpha v integrins. beta 1-null keratinocytes were characterised by poor
      adhesion to various substrates, by a reduced proliferation rate and by a strongly
      impaired migratory capacity. In vivo, the loss of beta 1 integrins in
      keratinocytes caused a severe defect in wound healing. beta 1-null keratinocytes
      showed impaired migration and were more densely packed in the hyperproliferative
      epithelium. Surprisingly, their proliferation rate was not reduced in early
      wounds and even increased in late wounds. The failure in re-epithelialisation
      resulted in a prolonged inflammatory response, leading to dramatic alterations in
      the expression of important wound-regulated genes. Ultimately, beta 1-deficient
      epidermis did cover the wound bed, but the epithelial architecture was abnormal.
      These findings demonstrate a crucial role of beta 1 integrins in keratinocyte
      migration and wound re-epithelialisation. Movies available on-line

PMID- 11959838
TI  - A glimpse into the molecular entrails of endoderm formation.

PMID- 11959839
TI  - Requirement of fibroblast growth factor 10 in development of white adipose
      tissue.
AB  - Fibroblast growth factors (FGFs) are important intercellular signaling molecules
      in developmental processes. Here, we show that FGF10 is secreted by cultured
      preadipocytes and that prevention of FGF10 signaling inhibits the expression of
      C/EBPbeta and the subsequent differentiation of these cells. An active form of
      C/EBPbeta rescued differentiation of the cells in which FGF10 signaling was
      blocked. Development of white adipose tissue and the expression of C/EBPbeta in
      this tissue of FGF10 knockout mice were markedly reduced, and the ability of
      embryonic fibroblasts derived from FGF10 knockout mice to differentiate into
      adipocytes was impaired. Therefore, FGF10 plays an important role in
      adipogenesis, at least partly by contributing to the expression of C/EBPbeta
      through an autocrine/paracrine mechanism.

PMID- 11959840
TI  - Cell surface proteins Nasrat and Polehole stabilize the Torso-like extracellular
      determinant in Drosophila oogenesis.
AB  - Structural cell-surface and extracellular-matrix proteins modulate intercellular
      signaling events during development, but how this is achieved remains largely
      unknown. Here we identify a novel family of Drosophila proteins, Nasrat and
      Polehole, that coat the oocyte surface and play two roles: They mediate assembly
      of the eggshell, and act in the Torso RTK signaling pathway that specifies the
      terminal regions of the embryo. Nasrat and Polehole are essential for
      extracellular accumulation of Torso-like, a factor secreted during oogenesis that
      initiates Torso receptor activation. Stabilization of secreted factors by
      specialized pericellular proteins may be a general mechanism during signaling and
      developmental patterning.

PMID- 11959841
TI  - SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase
      that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc
      finger proteins.
AB  - Posttranslational modification of histones has emerged as a key regulatory signal
      in eukaryotic gene expression. Recent genetic and biochemical studies link H3
      lysine 9 (H3-K9) methylation to HP1-mediated heterochromatin formation and gene
      silencing. However, the mechanisms that target and coordinate these activities to
      specific genes is poorly understood. Here we report that the KAP-1 corepressor
      for the KRAB-ZFP superfamily of transcriptional silencers binds to SETDB1, a
      novel SET domain protein with histone H3-K9-specific methyltransferase activity.
      Although acetylation and phosphorylation of the H3 N-terminal tail profoundly
      affect the efficiency of H3-K9 methylation by SETDB1, we found that methylation
      of H3-K4 does not affect SETDB1-mediated methylation of H3-K9. In vitro
      methylation of the N-terminal tail of histone H3 by SETDB1 is sufficient to
      enhance the binding of HP1 proteins, which requires both an intact chromodomain
      and chromoshadow domain. Indirect immunofluoresence staining of interphase nuclei
      localized SETDB1 predominantly in euchromatic regions that overlap with HP1
      staining in nonpericentromeric regions of chromatin. Moreover, KAP-1, SETDB1, H3
      MeK9, and HP1 are enriched at promoter sequences of a euchromatic gene silenced
      by the KRAB-KAP-1 repression system. Thus, KAP-1 is a molecular scaffold that is
      targeted by KRAB-ZFPs to specific loci and coordinates both histone methylation
      and the deposition of HP1 proteins to silence gene expression.

PMID- 11959842
TI  - E2F mediates cell cycle-dependent transcriptional repression in vivo by
      recruitment of an HDAC1/mSin3B corepressor complex.
AB  - Despite biochemical and genetic data suggesting that E2F and pRB (pocket protein)
      families regulate transcription via chromatin-modifying factors, the precise
      mechanisms underlying gene regulation by these protein families have not yet been
      defined in a physiological setting. In this study, we have investigated promoter
      occupancy in wild-type and pocket protein-deficient primary cells. We show that
      corepressor complexes consisting of histone deacetylase (HDAC1) and mSin3B were
      specifically recruited to endogenous E2F-regulated promoters in quiescent cells.
      These complexes dissociated from promoters once cells reached late G1, coincident
      with gene activation. Interestingly, recruitment of HDAC1 complexes to promoters
      depended absolutely on p107 and p130, and required an intact E2F-binding site. In
      contrast, mSin3B recruitment to certain promoters did not require p107 or p130,
      suggesting that recruitment of this corepressor can occur via E2F-dependent and 
      independent mechanisms. Remarkably, loss of pRB had no effect on HDAC1 or mSin3B
      recruitment. p107/p130 deficiency triggered a dramatic loss of E2F4 nuclear
      localization as well as transcriptional derepression, which is suggested by
      nucleosome mapping studies to be the result of localized hyperacetylation of
      nucleosomes proximal to E2F-binding sites. Taken together, these findings show
      that p130 escorts E2F4 into the nucleus and, together with corepressor complexes
      that contain mSin3B and/or HDAC1, directly represses transcription from target
      genes as cells withdraw from the cell cycle.

PMID- 11959843
TI  - Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian
      cells.
AB  - RNA interference (RNAi) was first recognized in Caenorhabditis elegans as a
      biological response to exogenous double-stranded RNA (dsRNA), which induces
      sequence-specific gene silencing. RNAi represents a conserved regulatory motif,
      which is present in a wide range of eukaryotic organisms. Recently, we and others
      have shown that endogenously encoded triggers of gene silencing act through
      elements of the RNAi machinery to regulate the expression of protein-coding
      genes. These small temporal RNAs (stRNAs) are transcribed as short hairpin
      precursors (approximately 70 nt), processed into active, 21-nt RNAs by Dicer, and
      recognize target mRNAs via base-pairing interactions. Here, we show that short
      hairpin RNAs (shRNAs) can be engineered to suppress the expression of desired
      genes in cultured Drosophila and mammalian cells. shRNAs can be synthesized
      exogenously or can be transcribed from RNA polymerase III promoters in vivo, thus
      permitting the construction of continuous cell lines or transgenic animals in
      which RNAi enforces stable and heritable gene silencing.

PMID- 11959844
TI  - The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs
      required for cell division but not cell growth.
AB  - Plant microtubules are organized into specific cell cycle-dependent arrays that
      have been implicated in diverse cellular processes, including cell division and
      organized cell expansion. Mutations in four Arabidopsis genes collectively called
      the PILZ group result in lethal embryos that consist of one or a few grossly
      enlarged cells. The mutant embryos lack microtubules but not actin filaments.
      Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly,
      trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is
      normal. The four PILZ group genes were isolated by map-based cloning and are
      shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and
      E, and associated small G-protein Arl2 that mediate the formation of alpha/beta
      tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in
      cytosolic protein complexes and did not colocalize with microtubules. Another
      gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown
      to encode a TFC A ortholog. Our genetic ablation of microtubules shows their
      requirement in cell division and vesicle trafficking during cytokinesis, whereas
      cell growth is mediated by microtubule-independent vesicle trafficking to the
      plasma membrane during interphase.

PMID- 11959845
TI  - Control of neuronal subtype identity by the C. elegans ARID protein CFI-1.
AB  - The Caenorhabditis elegans hermaphrodite nervous system is composed of 302
      neurons that fall into at least 118 diverse classes. Here we describe cfi-1, a
      gene that contributes to the development of neuronal diversity. cfi-1 promotes
      appropriate differentiation of the URA sensory neurons and inhibits URA from
      expressing the male-specific CEM neuronal fate. The UNC-86 POU homeodomain
      protein is present in CEM and URA neurons, and can promote expression of CEM
      specific genes in both CEM and URA, but CFI-1 inhibits expression of these genes
      in the URA cells. cfi-1 also promotes appropriate differentiation and glutamate
      receptor expression in the AVD and PVC interneurons. cfi-1 encodes a conserved
      neuron- and muscle-restricted DNA-binding protein containing an A/T rich
      interaction domain (ARID). ARID proteins regulate early patterning and muscle
      fate in Drosophila, but they have not previously been implicated in the control
      of neuronal subtype identity.

PMID- 11959846
TI  - p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas.
AB  - Interactions between the p53 and PI3K/AKT pathways play a significant role in the
      determination of cell death/survival. In benign cells these pathways are
      interrelated through the transcriptional regulation of PTEN by p53, which is
      required for p53-mediated apoptosis. PTEN exerts its effects by decreasing the
      phosphorylated AKT fraction, thereby diminishing prosurvival activities. However,
      the link between these pathways in cancer is not known. In this study, PIK3CA,
      encoding the p110alpha catalytic subunit of PI3K, is identified as an oncogene
      involved in upper aerodigestive tract (UADT) carcinomas. Simultaneous
      abnormalities in both pathways are rare in primary tumors, suggesting that
      amplification of PIK3CA and mutation of p53 are mutually exclusive events and
      either event is able to promote a malignant phenotype. Moreover, the negative
      effect of p53 induction on cell survival involves the transcriptional inhibition
      of PIK3CA that is independent of PTEN activity, as PTEN is not expressed in the
      primary tumors. Conversely, constitutive activation of PIK3CA results in
      resistance to p53-related apoptosis in PTEN deficient cells. Thus, p53 regulates
      cell survival by inhibiting the PI3K/AKT prosurvival signal independent of PTEN
      in epithelial tumors. This inhibition is required for p53-mediated apoptosis in
      malignant cells.

PMID- 11959847
TI  - Regulation of the Neurospora circadian clock by casein kinase II.
AB  - Phosphorylation of clock proteins represents an important mechanism regulating
      circadian clocks. In Neurospora, clock protein FREQUENCY (FRQ) is progressively
      phosphorylated over time, and its level decreases when it is extensively
      phosphorylated. To identify the kinase phosphorylating FRQ and to understand the
      function of FRQ phosphorylation, a FRQ-phosphorylating kinase was purified and
      identified as casein kinase II (CKII). Disruption of the catalytic subunit gene
      of CKII in Neurospora resulted in hypophosphorylation and increased levels of FRQ
      protein. In addition, the circadian rhythms of frq RNA, FRQ protein, and clock
      controlled genes are abolished in the CKII mutant. Our data suggest that the
      phosphorylation of FRQ by CKII may have at least three functions; it decreases
      the stability of FRQ, reduces the protein complex formation between FRQ and the
      WHITE COLLAR proteins, and is important for the closing of the Neurospora
      circadian negative feedback loop. Taken together, our results suggest that CKII
      is an important component of the Neurospora circadian clock.

PMID- 11959849
TI  - Proteasome inhibitors reduce luciferase and beta-galactosidase activity in tissue
      culture cells.
AB  - Reporter enzymes are commonly used in cell biology to study transcriptional
      activity of genes. Recently, reporter enzymes in combination with compounds that
      inhibit proteasome function have been used to study the effect of blocking
      transcription factor degradation on gene activation. While investigating the
      effect of proteasome inhibition on steroid receptor activation of the mouse
      mammary tumor virus (MMTV) promoter, we found that treatment with proteasome
      inhibitors enhanced glucocorticoid activation of the promoter attached to a
      chloramphenicol acetyltransferase (CAT) reporter, but inhibited activation of
      MMTV attached to a firefly luciferase or beta-galactosidase reporter. MMTV RNA
      levels under these conditions correlated with the promoter activity observed
      using the CAT reporter, suggesting that proteasome inhibitor treatment interfered
      with luciferase or beta-galactosidase reporter assays. Washout experiments
      demonstrated that the majority of luciferase activity was lost if the proteasome
      inhibitor was added at the same time luciferase was produced, not once the
      functional protein was made, suggesting that proteasome inhibition interferes
      with production of luciferase protein. Indeed, we found that proteasome inhibitor
      treatment dramatically reduced the levels of luciferase and beta-galactosidase
      protein produced, as determined by Western blot. Thus, treatment with proteasome
      inhibitors interferes with luciferase and beta-galactosidase reporter assays,
      possibly by inhibiting production of a functional reporter protein.

PMID- 11959850
TI  - Kinetic mechanism of activation of the Cdk2/cyclin A complex. Key role of the C
      lobe of the Cdk.
AB  - Eukaryotic cell cycle progression is controlled by the ordered action of cyclin
      dependent kinases, activation of which occurs through the binding of the cyclin
      to the Cdk followed by phosphorylation of a conserved threonine in the T-loop of
      the Cdk by Cdk-activating kinase (CAK). Despite our understanding of the
      structural changes, which occur upon Cdk/cyclin formation and activation, little
      is known about the dynamics of the molecular events involved. We have
      characterized the mechanism of Cdk2/cyclin A complex formation and activation at
      the molecular and dynamic level by rapid kinetics and demonstrate here that it is
      a two-step process. The first step involves the rapid association between the
      PSTAIRE helix of Cdk2 and helices 3 and 5 of the cyclin to yield an intermediate
      complex in which the threonine in the T-loop is not accessible for
      phosphorylation. Additional contacts between the C-lobe of the Cdk and the N
      terminal helix of the cyclin then induce the isomerization of the Cdk into a
      fully mature form by promoting the exposure of the T-loop for phosphorylation by
      CAK and the formation of the substrate binding site. This conformational change
      is selective for the cyclin partner.

PMID- 11959848
TI  - A sporulation membrane protein tethers the pro-sigmaK processing enzyme to its
      inhibitor and dictates its subcellular localization.
AB  - The developmental transcription factor sigmaK is derived from the inactive
      precursor protein pro-sigmaK by regulated proteolysis during the process of
      sporulation in the bacterium Bacillus subtilis. The putative pro-sigmaK
      processing enzyme SpoIVFB is a member of a family of membrane-embedded
      metalloproteases and is held inactive by two other integral membrane proteins,
      SpoIVFA and BofA. Herein we show that the processing enzyme and its two
      regulators exist in a multimeric complex that localizes to the membrane
      surrounding the developing spore (the forespore). We further show that one of the
      regulators, SpoIVFA, plays a central role in both the formation of this complex
      and its subcellular localization. Evidence is presented in support of a model in
      which SpoIVFA acts as a platform for bringing BofA and SpoIVFB together, whereby
      BofA inhibits pro-sigmaK processing until a signal has been received from the
      forespore.

PMID- 11959851
TI  - A RING finger protein Praja1 regulates Dlx5-dependent transcription through its
      ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein,
      Dlxin-1.
AB  - Msx2 and Dlx5 are homeodomain proteins that play an important role in osteoblast
      differentiation and whose expression is induced by bone morphogenetic proteins.
      Recently we have identified a novel protein, Dlxin-1, that associates with these
      homeodomain proteins and regulates Dlx5-dependent transcriptional function
      (Masuda, Y., Sasaki, A., Shibuya, H., Ueno, N., Ikeda, K., and Watanabe, K.
      (2001) J. Biol. Chem. 276, 5331-5338). In an attempt to elucidate the molecular
      function of Dlxin-1, two closely related RING finger proteins, Praja1 and
      Neurodap-1, were isolated by yeast two-hybrid screening using the C-terminal
      necdin homology domain of Dlxin-1 as bait. Glutathione S-transferase pull-down
      and immunoprecipitation/Western blotting assays following co-transfection of
      Dlxin-1 and Praja1 revealed that Praja1 binds to the C-terminal necdin homology
      domain of Dlxin-1 in vitro and in vivo, respectively. Overexpression of Praja1
      caused a decrease in Dlxin-1 protein level, which was reversed when a proteasome
      inhibitor was added. Overexpression of Praja1 with a mutation in the RING finger
      inhibited the decrease in Dlxin-1 protein, pointing to the importance of
      ubiquitin-protein isopeptide ligase (E3) activity associated with RING finger.
      Wild-type Praja1, but not its RING finger mutant, promoted ubiquitination of
      Dlxin-1 in vivo. Finally, expression of Praja1 down-regulated Dlx5-dependent
      transcriptional activity in a GAL4-dependent assay. These results suggest that
      Praja1 regulates the transcription function of the homeodomain protein Dlx5 by
      controlling the stability of Dlxin-1 via an ubiquitin-dependent degradation
      pathway.

PMID- 11959852
TI  - Structure of the antimicrobial peptide tachystatin A.
AB  - The solution structure of antimicrobial peptide tachystatin A from the Japanese
      horseshoe crab (Tachypleus tridentatus) was determined by two-dimensional nuclear
      magnetic resonance measurements and distance-restrained simulated annealing
      calculations. The correct pairs of disulfide bonds were also confirmed in this
      study. The obtained structure has a cysteine-stabilized triple-stranded beta
      sheet as a dominant secondary structure and shows an amphiphilic folding observed
      in many membrane-interactive peptides. Interestingly, tachystatin A shares
      structural similarities with the calcium channel antagonist omega-agatoxin IVA
      isolated from spider toxin and mammalian defensins, and we predicted that omega
      agatoxin IVA also have the antifungal activity. These structural comparisons and
      functional correspondences suggest that tachystatin A and omega-agatoxin IVA may
      exert the antimicrobial activity in a manner similar to defensins, and we have
      confirmed such activity using fungal culture assays. Furthermore, tachystatin A
      is a chitin-binding peptide, and omega-agatoxin IVA also showed chitin-binding
      activities in this study. Tachystatin A and omega-agatoxin IVA showed no
      structural homology with well known chitin-binding motifs, suggesting that their
      structures belong to a novel family of chitin-binding peptides. Comparison of
      their structures with those of cellulose-binding proteins indicated that Phe(9)
      of tachystatin A might be an essential residue for binding to chitin.

PMID- 11959853
TI  - Actin-induced closure of the actin-binding cleft of smooth muscle myosin.
AB  - The putative actin-binding interface of myosin is separated by a large cleft that
      extends into the base of the nucleotide binding pocket, suggesting that it may be
      important for mediating the nucleotide-dependent changes in the affinity for
      myosin on actin. We have genetically engineered a truncated version of smooth
      muscle myosin containing the motor domain and the essential light chain-binding
      region (MDE), with a single tryptophan residue at position 425 (F425W-MDE) in the
      actin-binding cleft. Steady-state fluorescence of F425W-MDE demonstrates that Trp
      425 is in a more solvent-exposed conformation in the presence of MgATP than in
      the presence of MgADP or absence of nucleotide, consistent with closure of the
      actin-binding cleft in the strongly bound states of MgATPase cycle for myosin.
      Transient kinetic experiments demonstrate a direct correlation between the rates
      of strong actin binding and the conformation of Trp-425 in the actin-binding
      cleft, and suggest the existence of a novel conformation of myosin not previously
      seen in solution or by x-ray crystallography. Thus, these results directly
      demonstrate that: 1) the conformation of the actin-binding cleft mediates the
      affinity of myosin for actin in a nucleotide-dependent manner, and 2) actin
      induces conformational changes in myosin required to generate force and motion
      during muscle contraction.

PMID- 11959854
TI  - Transcriptional induction of CYP1A1 by oltipraz in human Caco-2 cells is aryl
      hydrocarbon receptor- and calcium-dependent.
AB  - Oltipraz, a synthetic derivative of the cruciferous vegetable product 1,2
      dithiole-3-thione, is considered as one of the most potent chemoprotectants. It
      modulates both cytochrome P-450 (CYP) and glutathione S-transferase expression
      and activities in rat tissues. Its effects, however, are variable according to
      the enzyme, tissue, and species. We show here that, as previously found in rat
      lung and kidney, CYP1A1 is inducible by oltipraz in both rat intestine and Caco-2
      cells, a cell line originated from a human colon adenocarcinoma. In these cells,
      a 50 microm oltipraz treatment increased CYP1A1 mRNA ( approximately 30-fold),
      protein and activity. mRNA level was augmented as early as 2 h after the
      beginning of treatment, suggesting a transcriptional activation, and was maximal
      between 8 and 12 h. Transient transfection of Caco-2 cells with constructs
      containing different sizes of the 5'-flanking region of the CYP1A1 gene upstream
      of the luciferase reporter gene showed an increase in luciferase activity in
      oltipraz-treated cells, which correlates with the presence of the xenobiotic
      responsive element (XRE). Furthermore we demonstrated that resveratrol, an
      antagonist of the aryl hydrocarbon (Ah) receptor, inhibited the induction of both
      CYP1A1 promoter activity and mRNA by oltipraz, supporting the involvement of the
      Ah receptor in this induction. In an attempt to further characterize the
      mechanism of CYP1A1 induction, we showed a rapid increase in intracellular
      calcium concentration upon treatment of Caco-2 cells with oltipraz. Moreover, the
      effect of this compound on CYP1A1 was strongly abolished in the presence of BAPTA
      AM, a well known chelator of intracellular calcium, and 2-aminoethyl
      diphenylborate, an inhibitor of store-operated calcium channels. These results
      bring the first demonstration that oltipraz activates transcription of the CYP1A1
      gene through the Ah receptor-XRE pathway in Caco-2 cells and that CYP1A1
      induction relies upon an increase of intracellular calcium concentration.

PMID- 11959855
TI  - A unique substrate binding mode discriminates membrane type-1 matrix
      metalloproteinase from other matrix metalloproteinases.
AB  - In our study, we characterized the substrate recognition properties of membrane
      type-1 matrix metalloproteinase (MT1-MMP; also known as MMP-14), a key enzyme in
      tumor cell invasion and metastasis. A panel of optimal peptide substrates for MT1
      MMP was identified using substrate phage display. The substrates can be
      segregated into four groups based on their degree of selectivity for MT1-MMP.
      Substrates with poor selectivity for MT1-MMP are comprised predominately of the
      Pro-X-X- downward arrow-X(Hy) motif that is recognized by a number of MMPs.
      Highly selective substrates lack the characteristic Pro at the P(3) position;
      instead they contain an Arg at the P(4) position. This P(4) Arg is essential for
      efficient hydrolysis and for selectivity for MT1-MMP. Molecular modeling
      indicates that the selective substrates adopt a linear conformation that extends
      along the entire catalytic pocket of MT1-MMP, whereas non-selective substrates
      are kinked at the conserved P(3) Pro residue. Importantly, the selective
      substrates can be made non-selective by insertion of a proline kink at P(3),
      without significantly reducing overall k(cat)/K(m) values. Altogether the study
      provides a structural basis for selective and non-selective substrate recognition
      by MT1-MMP. The findings in this report are likely to explain several aspects of
      MT1-MMP biology.

PMID- 11959856
TI  - 5'-,3'-inverted thymidine-modified antisense oligodeoxynucleotide targeting
      midkine. Its design and application for cancer therapy.
AB  - Oligodeoxynucleotides modified at both 5'- and 3'-ends with inverted thymidine
      (5'-,3'-inverted T) were introduced as new reagents for antisense strategies.
      These modifications were performed to make the oligodeoxynucleotides resistant to
      nucleases. The effectiveness of these oligodeoxynucleotides was evaluated in
      terms of inhibition of synthesis of midkine (MK), a heparin-binding growth
      factor, and consequent inhibition of growth of CMT-93 mouse rectal carcinoma
      cells. 5'-,3'-Inverted T antisense MK suppressed synthesis of MK by CMT-93 cells
      and their growth in culture. Furthermore, 5'-,3'-inverted T oligodeoxynucleotides
      exhibited less cytotoxicity and better stability than phosphorothioate
      oligodeoxynucleotides. When 5'-,3'-inverted T antisense MK was mixed with
      atelocollagen, and injected into CMT-93 tumors pregrown in nude mice, tumor
      growth was markedly suppressed as compared with tumors injected with sense
      controls. The suppressive effect of 5'-,3'-inverted T antisense MK on tumor
      growth was stronger than that of phosphorothioate antisense MK. These findings
      indicated the usefulness of inverted thymidine-modified antisense
      oligodeoxynucleotides as a new reagent instead of phosphorothioate-modified
      oligodeoxynucleotides.

PMID- 11959857
TI  - Alternate substrate inhibition of cholesterol esterase by thieno[2,3
      d][1,3]oxazin-4-ones.
AB  - In a kinetic study, the interaction of bovine pancreatic cholesterol esterase
      (CEase) with fused 1,3-oxazin-4-ones and 1,3-thiazin-4-ones was investigated, and
      the compounds were characterized as alternate substrate inhibitors. Inhibition
      assays were performed in the presence of sodium taurocholate with p-nitrophenyl
      butyrate as chromogenic substrate. Strong active site-directed inhibition was
      detected for 2-diethylaminothieno[2,3-d][1,3]oxazin-4-ones with a cycloaliphatic
      chain at positions 5,6. The most potent inhibitors, compounds 3 and 4, exhibited
      K(i) values of 0.58 and 1.86 microm, respectively. An exchange of the ring oxygen
      by sulfur and the removal of the cycloaliphatic moiety as well as the replacement
      of the thiophene ring by benzene led to a loss of inhibitory potency. CEase has
      the capability to catalyze the hydrolysis of representatives of fused 1,3-oxazin
      4-ones as well as the highly stable 1,3-thiazin-4-ones by using an acylation
      deacylation mechanism. Hydrolyses were performed in the presence of a high enzyme
      concentration, and products were identified spectrophotometrically and by means
      of high performance liquid chromatography. The kinetic parameters V(max)I and
      V(max)I/K(m)(I) for the CEase-catalyzed turnover were determined. The compounds
      whose enzyme-catalyzed hydrolysis followed first-order kinetics (K(m)(I) > 25
      microm) failed to inhibit CEase. On the other hand, inhibitors 3 (initial
      concentration of 25 microm) and 4 (20 microm) were hydrolyzed by CEase under
      steady-state conditions in the first phase of the reaction. Rate-limiting
      deacylation was demonstrated in nucleophilic competition experiments with ethanol
      as acyl acceptor wherein the conversion of compound 3 was accelerated up to an
      ethanol concentration of 1.5 m. The characterization of these compounds (i.e. 3
      and 4) as alternate substrate inhibitors is not only based on the verification of
      the CEase-catalyzed hydrolysis. It also rests upon the concurrence of
      corresponding K(i) values obtained in the inhibition assay compared with
      separately determined K(m)(I) values of their enzyme-catalyzed consumption, as
      could be predicted from the kinetic model used in this study.

PMID- 11959858
TI  - Pseudomonas aeruginosa aspartate transcarbamoylase. Characterization of its
      catalytic and regulatory properties.
AB  - Aspartate transcarbamoylase from Pseudomonadaceae is a class A enzyme consisting
      of six copies of a 36-kDa catalytic chain and six copies of a 45-kDa polypeptide
      of unknown function. The 45-kDa polypeptide is homologous to dihydroorotase but
      lacks catalytic activity. Pseudomonas aeruginosa aspartate transcarbamoylase was
      overexpressed in Escherichia coli. The homogeneous His-tagged protein isolated in
      high yield, 30 mg/liter of culture, by affinity chromatography and crystallized.
      Attempts to dissociate the catalytic and pseudo-dihydroorotase (pDHO) subunits or
      to express catalytic subunits only were unsuccessful suggesting that the pDHO
      subunits are required for the proper folding and assembly of the complex. As
      reported previously, the enzyme was inhibited by micromolar concentrations of all
      nucleotide triphosphates. In the absence of effectors, the aspartate saturation
      curves were hyperbolic but became strongly sigmoidal in the presence of low
      concentrations of nucleotide triphosphates. The inhibition was unusual in that
      only free ATP, not MgATP, inhibits the enzyme. Moreover, kinetic and binding
      studies with a fluorescent ATP analog suggested that ATP induces a conformational
      change that interferes with the binding of carbamoyl phosphate but has little
      effect once carbamoyl phosphate is bound. The peculiar allosteric properties
      suggest that the enzyme may be a potential target for novel chemotherapeutic
      agents designed to combat Pseudomonas infection.

PMID- 11959860
TI  - HIV-1 Tat protein-mediated transactivation of the HIV-1 long terminal repeat
      promoter is potentiated by a novel nuclear Tat-interacting protein of 110 kDa,
      Tip110.
AB  - Human immunodeficiency virus type 1 (HIV-1) gene expression and replication is
      highly dependent on and modulated by interactions between viral and host cellular
      factors. Tat protein, encoded by one of the HIV-1 regulatory genes, tat, is
      essential for HIV-1 gene expression. A number of host cellular factors have been
      shown to interact with Tat in this process. During our attempts to determine the
      molecular mechanisms of Tat interaction with brain cells, we isolated a cDNA
      clone that encodes a novel Tat-interacting protein of 110 kDa or Tip110 from a
      human fetal brain cDNA library. GenBank BLAST search revealed that Tip110 was
      almost identical to a previously cloned KIAA0156 gene with unknown functions. In
      vivo binding of Tip110 with Tat was confirmed by immunoprecipitation and Western
      blotting, in combination with mutagenesis. The yeast three-hybrid RNA-protein
      interaction assay indicated no direct interaction of Tip110 with Tat
      transactivating response element RNA. Nevertheless, Tip110 strongly synergized
      with Tat on Tat-mediated chloramphenicol acetyltransferase reporter gene
      expression and HIV-1 virus production, whereas down-modulation of constitutive
      Tip110 expression inhibited HIV-1 virus production. Northern blot analysis showed
      that Tip110 mRNA was expressed in a variety of human tissues and cells. Moreover,
      digital fluorescence microscopic imaging revealed that Tip110 was expressed
      exclusively in the nucleus, and within a nuclear speckle structure that has
      recently been described for human cyclin T and CDK9, two critical components for
      Tat transactivation function on HIV-1 long terminal repeat promoter. Taken
      together, these data demonstrate that Tip110 regulates Tat transactivation
      activity through direct interaction, and suggest that Tip110 is an important
      cellular factor for HIV-1 gene expression and viral replication.

PMID- 11959859
TI  - Functional characterization of two novel mammalian electrogenic proton-dependent
      amino acid cotransporters.
AB  - We cloned two cDNAs encoding proton/amino acid cotransporters, designated as
      mPAT1 and mPAT2, from murine tissues. They were identified by sequence similarity
      to the amino acid/auxin permease family member of lower eukaryotes. We
      functionally characterized both transporters by flux studies and
      electrophysiology after expression in Xenopus laevis oocytes. Both mPAT1 and
      mPAT2 induced a pH-dependent electrogenic transport activity for small amino
      acids (glycine, alanine, and proline) that is altered by membrane potential.
      Direct evidence for amino acid/H(+)-symport was shown by intracellular
      acidification, and a flux coupling stoichiometry for proline/H(+)-symport of 1:1
      was determined for both transporters. Besides small apolar L-amino acids, the
      transporters also recognize their D-enantiomers and selected amino acid
      derivatives such as gamma-aminobutyric acid. The mPAT1 transporter, the murine
      orthologue of the recently cloned rat LYAAT-1 transporter, can be considered as a
      low affinity system when compared with mPAT2. The mRNA of mPAT1 is highly
      expressed in small intestine, colon, kidney, and brain; the mPAT2-mRNA is mainly
      found in heart and lung. Phenotypically, the PAT1 transporter possesses the same
      functional characteristics as the previously described proton-dependent amino
      acid transport process in apical membranes of intestinal and renal epithelial
      cells.

PMID- 11959861
TI  - A novel dual specificity phosphatase SKRP1 interacts with the MAPK kinase MKK7
      and inactivates the JNK MAPK pathway. Implication for the precise regulation of
      the particular MAPK pathway.
AB  - Mitogen-activated protein kinases (MAPKs) are activated in response to various
      extracellular stimuli, and their activities are regulated by upstream activating
      kinases and protein phosphatases such as MAPK phosphatases (MKPs). We report the
      identification and characterization of a novel MKP termed SKRP1 (SAPK pathway
      regulating phosphatase 1). It contains an extended active site sequence motif
      conserved in all MKPs but lacks a Cdc25 homology domain. Immunoblotting analysis
      revealed that SKRP1 is constitutively expressed, and its transcripts of 4.0 and
      1.0 kb were detected in almost tissues examined. SKRP1 was highly specific for c
      Jun N-terminal kinase (JNK) in vitro and effectively suppressed the JNK
      activation in response to tumor necrosis factor alpha or thapsigargin. Endogenous
      SKRP1 was present predominantly in the cytoplasm and co-localized with JNK.
      However, SKRP1 does not bind directly to its target JNK, but co-precipitation of
      SKRP1 with the MAPK kinase MKK7, a JNK activator, was found in vitro and in vivo.
      Furthermore, we found that SKRP1 did not interfere with the co-precipitation of
      MKK7 with JNK. Together, our findings indicate that SKRP1 interacts with its
      physiological substrate JNK through MKK7, thereby leading to the precise
      regulation of JNK activity in vivo.

PMID- 11959862
TI  - Scaffold role of a mitogen-activated protein kinase phosphatase, SKRP1, for the
      JNK signaling pathway.
AB  - Stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1)
      has been identified as a member of the mitogen-activated protein kinase (MAPK)
      phosphatase (MKP) family that interacts physically with the MAPK kinase (MAPKK)
      MKK7, a c-Jun N-terminal kinase (JNK) activator, and inactivates the MAPK JNK
      pathway. Although these findings indicated that SKRP1 contributes to the precise
      regulation of JNK signaling, it remains to be elucidated how SKRP1 is integrated
      into this pathway. We report that SKRP1 also plays a scaffold role for the JNK
      signaling, judged by the following observations. SKRP1 selectively formed the
      stable complexes with MKK7 but not with MKK4 and biphasically regulated the MKK7
      activity and MKK7-induced gene transcription in vivo. Co-precipitation analysis
      between SKRP1 and MKK7-activating MAPKK kinases (MAPKKKs) revealed that SKRP1
      also interacted with the MAPKKK, apoptosis signal-regulating kinase 1 (ASK1), but
      not with MAP kinase kinase kinase 1 (MEKK1). Consistent with these findings,
      SKRP1 expression increased the ASK1-MKK7 complexes in a dose-dependent manner and
      specifically enhanced the activation of MKK7 by ASK1. Thus, our findings are, to
      our knowledge, the first evidence to show that an MKP also functions as a
      scaffold protein for the particular MAPK signaling.

PMID- 11959863
TI  - Calcium-sensitive phospholipid binding properties of normal and mutant ferlin C2
      domains.
AB  - Mutations in dysferlin, a novel membrane protein of unknown function, lead to
      muscular dystrophy. Myoferlin is highly homologous to dysferlin and like
      dysferlin is a plasma membrane protein with six C2 domains highly expressed in
      muscle. C2 domains are found in a variety of membrane-associated proteins where
      they have been implicated in calcium, phospholipid, and protein-binding. We
      investigated the pattern of dysferlin and myoferlin expression in a cell culture
      model of muscle development and found that dysferlin is expressed in mature
      myotubes. In contrast, myoferlin is highly expressed in elongated "prefusion"
      myoblasts and is decreased in mature myotubes where dysferlin expression is
      greatest. We tested ferlin C2 domains for their ability to bind phospholipid in a
      calcium-sensitive manner. We found that C2A, the first C2 domain of dysferlin and
      myoferlin, bound 50% phosphatidylserine and that phospholipid binding was
      regulated by calcium concentration. A dysferlin point mutation responsible for
      muscular dystrophy was engineered into the dysferlin C2A domain and demonstrated
      reduced calcium-sensitive phospholipid binding. Based on these data, we propose a
      mechanism for muscular dystrophy in which calcium-regulated phospholipid binding
      is abnormal, leading to defective maintenance and repair of muscle membranes.

PMID- 11959864
TI  - DGAT1 is not essential for intestinal triacylglycerol absorption or chylomicron
      synthesis.
AB  - Dietary triacylglycerols are a major source of energy for animals. The absorption
      of dietary triacylglycerols involves their hydrolysis to free fatty acids and
      monoacylglycerols in the intestinal lumen, the uptake of these products into
      enterocytes, the resynthesis of triacylgylcerols, and the incorporation of newly
      synthesized triacylglycerols into nascent chylomicrons for secretion. In
      enterocytes, the final step in triacylglycerol synthesis is believed to be
      catalyzed primarily through the actions of acyl-CoA:diacylglycerol
      acyltransferase (DGAT) enzymes. In this study, we analyzed intestinal
      triacylglycerol absorption and chylomicron synthesis and secretion in DGAT1
      deficient (Dgat1(-/-)) mice. Surprisingly, DGAT1 was not essential for
      quantitative dietary triacylglycerol absorption, even in mice fed a high fat
      diet, or for the synthesis of chylomicrons. However, Dgat1(-/-) mice had reduced
      postabsorptive chylomicronemia (1 h after a high fat challenge) and accumulated
      neutral-lipid droplets in the cytoplasm of enterocytes when chronically fed a
      high fat diet. These results suggest a reduced rate of triacylglycerol absorption
      in Dgat1(-/-) mice. Analysis of intestine from Dgat1(-/-) mice revealed activity
      for two other enzymes, DGAT2 and diacylglycerol transacylase, that catalyze
      triacylglycerol synthesis and apparently help to compensate for the absence of
      DGAT1. Our findings indicate that multiple mechanisms for triacylglycerol
      synthesis in the intestine facilitate triacylglycerol absorption.

PMID- 11959865
TI  - Ikaros-CtIP interactions do not require C-terminal binding protein and
      participate in a deacetylase-independent mode of repression.
AB  - Ikaros and Aiolos are Kruppel zinc finger proteins that play key roles in hemo
      lymphoid development and homeostasis. We have previously shown that they can
      repress transcription through the recruitment of histone deacetylases (HDACs).
      Here, we provide the first functional evidence that these proteins can also
      repress gene function in a manner that does not require deacetylase activity.
      This functionality can be attributed in part to Ikaros interactions with the HDAC
      independent corepressor, C-terminal binding protein (CtBP). However, mutations
      that block Ikaros-CtBP interactions do not abolish Ikaros's repression activity,
      implicating the involvement of additional corepressors. Consistent with this
      expectation, we show that Ikaros can interact with a CtBP-interacting protein
      (CtIP), which has also been linked to a deacetylase-independent strategy of
      repression. Despite being a CtBP interactor, CtIP's association with Ikaros does
      not require CtBP but instead relies upon its Rb interaction domain.
      Significantly, Ikaros can interact with Rb, which itself can repress gene
      function in a deacetylase-independent manner. A mutation in Ikaros that abrogates
      CtIP interactions significantly reduces repression, and a double mutation that
      prevents interaction with both CtIP and CtBP even further alleviates repression.
      Finally, we show that CtIP and CtBP can interact with the general transcription
      factors, TATA binding protein and transcription factor IIB, which suggests a
      possible mechanism for their deacetylase-independent mode of repression.

PMID- 11959866
TI  - Primary structure and characteristics of a lectin from skin mucus of the Japanese
      eel Anguilla japonica.
AB  - Two types of lactose-binding lectins, AJL-1 and AJL-2, were purified from the
      skin mucus extract of the Japanese eel Anguilla japonica by lactose affinity
      chromatography and subsequent gel filtration. The molecular masses of AJL-1 and
      AJL-2 were 16,091 and 31,743 Da, respectively. Intact AJL-1 was comprised of two
      identical 16-kDa subunits having blocked N termini and no disulfide bonds. AJL-2
      was a homodimer with disulfide bonds. Based on the N-terminal amino acid sequence
      of the AJL-2 monomer, the nucleotide sequence of cDNA encoding this lectin was
      determined by 3'- and 5'-rapid amplification of cDNA ends. The deduced amino acid
      sequence showed approximately 30% homology with C-type lectins, which bind to
      carbohydrates in a Ca(2+)-dependent manner. In addition, AJL-2 exhibited highly
      conserved consensus amino acid residues of the C-type carbohydrate recognition
      domain, although this lectin showed Ca(2+)-independent activity. Gene expression
      of AJL-2 was detected only in the skin by Northern blot analysis, and this lectin
      localization was demonstrated in the club cells by immunohistochemistry. These
      results indicate that AJL-2 is secreted on the body surface and function as a
      component of skin mucus. AJL-2 agglutinated Escherichia coli and suppressed its
      growth, suggesting that this lectin is involved in host defense.

PMID- 11959867
TI  - Computer-assisted mutagenesis of ecotin to engineer its secondary binding site
      for urokinase inhibition.
AB  - Inhibitors of urokinase-type plasminogen activator (uPA) were selected in vitro
      from two ecotin phage-display libraries to study the effect on binding of amino
      acid substitutions at critical positions 108, 110, 112, and 113 within the 100s
      loop (RNKL, respectively, in wild type ecotin). The first, a focused library, was
      the result of a computation-assisted approach using the three-dimensional
      structure of the ecotin-trypsin complex to guide the modeling of amino acid
      substitutions predicted to increase affinity for uPA. The second, a complete
      library, allowed for all substitutions at the above identified positions. The
      consensus sequences selected from the focused, and complete libraries were RRWS
      and R(R/N)QL, respectively. Inhibition constant determinations showed ecotin
      variants containing these sequences to be similarly potent (K(i) = 1-2 nm). These
      substitutions were combined with previously identified substitutions in another
      critical region of ecotin. One of these combinations (D70R/M84R/RRQL) is the
      tightest (K(i) = 50 pm) ecotin variant inhibitor of uPA. The blending of
      combinatorial methods and computer algorithms designed to predict stronger
      binders has allowed us to obtain protein derivatives that exhibit greatly
      increased affinity for a predetermined target. This technology can be applied to
      select for enhanced binding interactions at protein-protein interfaces and
      accelerate the process of protease inhibitor development.

PMID- 11959868
TI  - Effect of polymerization on the subdomain 3/4 loop of yeast actin.
AB  - The Holmes F-actin model predicts a polymerization-dependent conformation change
      of a subdomain 3/4 loop with a hydrophobic tip (residues 266-269), allowing
      interaction with a hydrophobic surface on the opposing strand of the filament
      producing filament stabilization. We introduced cysteines in place of Val(266),
      Leu(267), and Leu(269) in yeast actin to allow attachment of pyrene maleimide.
      Pyrene at each of these positions produced differing fluorescence spectra in G
      actin. Polymerization decreased the fluorescence for the 266 and 267 probes and
      increased that for the 269 probe. The direction of the fluorescence change was
      mirrored with a smaller and less hydrophobic probe, acrylodan, when attached to
      266 or 269. Following polymerization, increased acrylamide quenching was observed
      for pyrene at 266 or 267 but not 269. The 267 probe was the least accessible of
      the three in G- and F-actin. F-actin quenching was biphasic for the 265, 266, and
      269 but not 267 probes, suggesting that in F-actin, the pyrene samples multiple
      environments. Finally, in F-actin the probe at 266 interacts with one at Cys(374)
      on a monomer in the opposing strand, producing a pyrene excimer band. These
      results indicate a polymerization-dependent movement of the subdomain 3/4 loop
      partially consistent with Holmes' model.

PMID- 11959870
TI  - Cancer control in Australia: into the 21(st) Century.
AB  - Australia ranks highly internationally for cancer control, in part because cancer
      registries provide comprehensive national incidence and mortality and other
      cancer data annually. This has facilitated short- and long-term planning over the
      last quarter of a century. For example, male death rates from lung cancer in
      Australia peaked around 1985 and are now falling steeply, whereas female rates
      are still rising. In women, cervical cancer incidence and mortality have fallen
      owing to cervical screening over the last quarter of a century. Breast cancer
      mortality is now trending downwards after a half-century plateau, probably
      because of better treatment protocols. Cancer registry based State and national
      population treatment surveys over the last 15 years have identified both
      deficiencies and strengths in evidenced-based treatment of cancer in Australia.
      For example, in the State of Victoria, 5-yearly population based breast cancer
      treatment surveys have shown that the proportion of women who had a mastectomy
      versus a lumpectomy as their primary surgical operation fell from 78% in 1986 to
      47% 1995. All Australians are covered by a universal health care system.
      Therefore, socio-economic status is not a barrier to accessing high quality
      cancer control, whether it be prevention, screening, treatment or education. In
      addition, non-government organizations (NGOs) specializing in cancer control have
      been providing free or highly subsidized support services to patients and their
      families for over half a century in most states. These NGOs have also been very
      active in public education about cancer, especially cancer prevention.

PMID- 11959871
TI  - The strategy for esophageal cancer control in high-risk areas of China.
AB  - Even though the mortality from esophageal cancer has decreased during the last
      two decades nationwide in China, the mortality from esophageal cancer in high
      risk areas is still at a high level. Moreover, the 5-year survival rate of
      patients with resectable esophageal cancer after treatment ranges between 20 and
      30%, as majority of patients with esophageal cancer were diagnosed in late
      stages. Therefore, esophageal cancer control in high-risk areas in China remains
      a critical task. A strategy is proposed that the high-risk population would be
      screened by endoscopy with mucosal iodine staining and biopsy of all unstained
      lesions and diagnosis of severe dysplasia carcinoma in situ, and intra-mucosal
      carcinoma could be cured by radical mucosectomy. A pilot study showed that the
      strategy is feasible and cost-effective for the high prevalence of premalignant
      lesions and carcinomas in early stages. It would be expected that the mortality
      from esophageal cancer could be decreased in high-risk areas if the proposed
      strategy is carried out on a large scale.

PMID- 11959872
TI  - Cancer control efforts in the Indian subcontinent.
AB  - The Indian subcontinent in South Asia occupies 2.4% of the world land mass and is
      home to 16.5% of the world population. At present, it is roughly estimated that
      approximately 1 million new cancer cases per annum will be recorded and at any
      given time there will be 3 million cancer patients in India. Nevertheless, cancer
      is not a frequent disease for the Indian population. Cancer statistics
      demonstrate that cancers frequently observed in India are lifestyle dependent,
      with offending factors such as tobacco usage, low socio-economic status, multiple
      pregnancies and poor sexual hygiene. These factors are closely related to the
      population living in rural surroundings and they are targets for cancer
      prevention. Low socio-economic status and low literacy rates ensure that most
      patients are diagnosed at an advanced stage of the disease. It is very difficult
      for these patients to achieve a cure and they are always treated by palliative
      care with much cost and morbidity. Therefore, it is reasonable to postulate that
      the strategy for cancer control in India should be focused on health education
      for the rural population and the creation of an infrastructure for cancer
      management. These systems with appropriate low-cost technology might be able to
      be duplicated as a model for developing countries with low capital inputs.

PMID- 11959873
TI  - Cancer in Indonesia, present and future.
AB  - Cancer control has been in effect in Indonesia since the early 1920s. It was the
      Dutch Colonial Government who started with the Institution for Cancer Control,
      which was closed by the Japanese Occupation Administration between 1942 and 1945.
      After the independence of the Republic of Indonesia, a Cancer Control Foundation
      was established in 1962. At present, clinical and non-clinical departments in
      government teaching hospitals (there are 13 teaching hospitals) usually handle
      all cancer problems. In 1993, Dharmais Cancer Center in Jakarta was established
      and has become the top referral cancer hospital for Indonesia. Until now, there
      have been no nationwide accurate data on cancer registration, owing to a lack of
      funds and manpower. Cancer data collection is usually provided as a relative
      frequency study from several departments of the teaching hospitals. It is
      currently estimated that there will be at least 170-190 new cancer cases annually
      for each 100 000 people. The most frequent and primary cancers are cervix,
      breast, lymph node, skin and nasopharynx. Since Indonesia is now in a transition
      phase and has many problems concerning the economy and health care, we suggested
      a well-planned cancer control program. It includes the primary, secondary and
      tertiary prevention of cancer in cities, where inhabitants can afford to
      subsidize a certain proportion of the budgets for the implementation of this
      program.

PMID- 11959874
TI  - Overview of cancer control programs in Japan.
AB  - Japan has a population of about 127 million, with an average life expectancy that
      is one of the highest in the world. Cancer has been the leading cause of death in
      Japan since 1981. The incidence of cancer for all sites in 1994 was estimated to
      be 440 000; crude incidence rates per 100 000 for males and females were 416.3
      and 299.4, respectively. In 1997, the number of cancer deaths was 275 413; crude
      death rates for males and females per 100 000 were 273.0 and 169.9, respectively.
      Projections for 2015 indicate that 890 000 people will develop cancer and 450 000
      will die as a result. It is not too much to say that Japan is now amid a 'Cancer
      Era'. Meanwhile, the progress in medical sciences is improving survival in cancer
      patients; in cancer patients diagnosed during 1987-89, relative 5-year survival
      was reported to be 41.2% for all sites and cancer survivorship research estimated
      the number of cancer survivors for all sites in 1998 who have lived for between 5
      and 24 years after diagnosis to be 1.5 million. The Ministry of Health and
      Welfare is focusing on five different measures in the implementation of its
      cancer control programs: public health education, nationwide cancer screening
      programs, development and support of specialized medical institutions, training
      of specialists and promotion of basic and clinical cancer research. As a tool for
      public health education, the Ministry published in 2000 a 10-year health
      promotion program entitled 'Healthy Japanese in the 21st Century'. In the plan,
      seven particular goals are enumerated with regard to cancer. In practice, issues
      of concern include the development of new modalities, telling the truth to cancer
      patients, clinical trials and bioethical issues.

PMID- 11959875
TI  - Cancer in Korea: present features.
AB  - In 1995, more than 50 000 persons died in Korea due to cancers and around 230 000
      cancer patients were under medical treatment. Cancer patients accounted for 8.3%
      of all inpatients. The medical care expenditure for cancer patients accounted for
      15-18% of all expenditure for inpatients. The age standardized annual incidence
      rate of all cancers in the period 1992-95 was 290.8 per 100 000 in males and
      173.4 in females. The cumulative rates for the age span 0-74 years were 35.8% in
      males and 20% in females. Four cancer sites, stomach, liver, lung and colorectum,
      comprise two-thirds of all new cancers in males. For females, the major sites
      include uterine cervix and breast in addition to the above four sites. The age
      adjusted cancer death rate in 1995 was 179.0 in males and 73.5 in females, which
      accounted for 24.1 and 17.7% of all deaths in males and females, respectively.
      Some changing patterns of major cancers were observed, especially in the older
      age group. Early detection programs for specific cancer sites such as stomach,
      liver, colorectum, breast and uterine cervix have been adopted and conducted
      since 1992 by several medical insurance companies. However, it was not until 1995
      that the Korean government considered a national cancer control program. In 1995,
      the 'Ten Year Plan for Cancer Control, Korea' was formulated and the government
      adopted the plan as a national policy in 1996. The economic crisis in Korea in
      1997, however, hindered carrying out the plan.

PMID- 11959876
TI  - Overview of cancer in Malaysia.
AB  - The problem of cancer in Malaysia is a growing one. It is now the fourth leading
      cause of death among medically certified deaths. Cancer of the lung is the most
      common killer among malignancies. It is estimated that the annual incidence of
      cancer is 30 000. The majority of patients are found at a late stage of the
      disease. The National Cancer Control Program aims to reduce the incidence and
      mortality of cancer and to improve the quality of life of cancer patients.
      Policies encompass prevention, early diagnosis, treatment, palliative care and
      rehabilitation. The program for prevention includes an anti-smoking campaign and
      immunization of babies against hepatitis B. Papanicolaou's smear and breast self
      examination are among efforts for the early detection of cancer. Public education
      and the promotion of healthy lifestyles have been actively carried out.
      Facilities for treatment and palliative care are being developed further.
      Networks between the public and private sectors and non-governmental
      organizations have been on-going. Apart from the establishment and upgrading of
      treatment facilities, the need for training of skilled staff in the treatment of
      cancer is highlighted.

PMID- 11959877
TI  - Developing areas in cancer in New Zealand.
AB  - New Zealand has a cancer profile similar to those of Western developed countries,
      with a high rate of melanoma, similar to Australia. Statistics separating the
      Maori from the non-Maori population, although open to difficulties in
      interpretation, show higher rates in Maori of liver, stomach, lung and cervix
      uterine cancer and lower rates of colorectal cancer and of melanoma. Screening
      and prevention programmes are limited by resource constraints; there is
      population screening for cervical cancer and breast cancer screening is being
      developed. Screening for hepatitis B and liver cancer is proposed, despite
      conflicting scientific opinions, while screening for colorectal cancer is not
      planned, despite randomized trial evidence of benefit. There is no clear national
      cancer control programme at present. Investigation of stomach cancer in Maori
      families had identified a new gene.

PMID- 11959878
TI  - Cancer and the Philippine Cancer Control Program.
AB  - Cancer is the third leading cause of morbidity and mortality in the Philippines.
      Leading cancer sites/types are lung, breast, cervix, liver, colon and rectum,
      prostate, stomach, oral cavity, ovary and leukemia. There is at present a low
      cancer prevention consciousness and most cancer patients seek consultation only
      at advanced stages. Cancer survival rates are relatively low. The Philippine
      Cancer Control Program, begun in 1988, is an integrated approach utilizing
      primary, secondary and tertiary prevention in different regions of the country at
      both hospital and community levels. Six lead cancers (lung, breast, liver,
      cervix, oral cavity, colon and rectum) are discussed. Features peculiar to the
      Philippines are described; and their causation and prevention are discussed. A
      recent assessment revealed shortcomings in the Cancer Control Program and urgent
      recommendations were made to reverse the anticipated 'cancer epidemic'. There is
      also today in place a Community-based Cancer Care Network which seeks to develop
      a network of self-sufficient communities sharing responsibility for cancer care
      and control in the country.

PMID- 11959879
TI  - An overview of the cancer control programme in Singapore.
AB  - Singapore is a multiracial, multireligious and multicultural society. Today,
      cancer is the leading cause of death in Singapore and about one in four deaths is
      from cancer. The Singapore Cancer Registry has been in existence for more than 25
      years and its accuracy of data for incidence, distribution, changing patterns,
      etc., is close to 100%. These statistics revealed that the incidence of cancer is
      related to the racial distribution of the population. A national concerted cancer
      control programme is targeted at prevention, early detection and integrated
      management. Strong laws against smoking and a national vaccination programme
      against hepatitis are in place.

PMID- 11959880
TI  - Cancer epidemiology and control in Taiwan: a brief review.
AB  - Malignant neoplasm has become the leading cause of death in Taiwan since 1982.
      There has been a decreasing trend for cancers of the stomach and cervix uteri,
      while an increasing trend has been observed for cancers of the lung, liver, oral
      cavity, colon and rectum, breast and prostate. International comparison and
      migrant studies have shown an elevated risk of hepatocellular carcinoma,
      nasopharyngeal carcinoma and cervical neoplasia in Taiwan. The national hepatitis
      B vaccination program, started in July 1984, has resulted in a significant
      decrease in childhood hepatocellular carcinoma in Taiwan. A decrease in
      prevalence of cigarette smoking has been observed among middle-aged men since the
      control of tobacco hazards was enacted in 1997. Free mass screening of cervical
      neoplasia and colorectal cancer has been implemented in the national health
      insurance program since 1995. Project-based screening for hepatocellular
      carcinoma, nasopharyngeal carcinoma and breast cancer among high-risk groups was
      started in 1994. Most cancer patients are diagnosed by pathological examinations
      and treated by surgical operation, chemotherapy and radiotherapy in major
      teaching hospitals in Taiwan. The Taiwan Collaborative Oncology Group has been
      organized to assess the efficacy of various treatment modalities through
      multicentric clinical trials. There has been a striking increase in expenditure
      for medical care of cancer patients. Cancer researchers mainly sponsored by the
      National Science Council and Department of Health are engaged in basic,
      epidemiological and clinical studies on major cancers in Taiwan. Major fields of
      the research include cancer genomics, gene therapy, molecular epidemiology and
      DNA vaccine.

PMID- 11959881
TI  - Cancer control in Thailand.
AB  - Cancer in Thailand is becoming a significant health problem. It is the leading
      cause of death in Thailand. Several cancers can be prevented by a nationwide
      campaign of health education to prevent raw fish intake and an antismoking
      campaign. An appropriate cervical cancer and breast cancer screening program can
      improve the recent prevalence of both and lead to better results of treatment.
      Research related to the carcinogenesis mechanism of certain cancers can lead to
      greater understanding and a better plan of control.

PMID- 11959882
TI  - The situation with cancer control in Vietnam.
AB  - Vietnam is one of the poor, developing countries. Malnutrition and infectious
      diseases are still major health problems. Cancer ranks in a relatively modest
      position of priority. The reason is partly explained by a shortage of treatment
      facilities and poor quality of health and vital statistics. The leading cancers
      in the country are lung, liver, stomach, colon-rectum and nasopharynx in males
      and breast, cervix, stomach, liver, colon-rectum and lung in females. Although
      the country has some common patterns of cancer such as a relatively high
      incidence of nasopharynx, liver and stomach and a relatively low incidence of
      breast and prostate cancer compared with international data, the geographical
      distribution of cancer is not homogenous within the country. The most remarkable
      difference is observed in cancer of the cervix uteri, of which the incidence in
      the South is, at least four times higher than that in the North. Other less
      extensive differences are observed in cancer of the lung, stomach, nasopharynx
      and breast, the incidence of which seems to be higher in the North than in the
      South, and the liver, which seems to be more frequent in the South than in the
      North. It was estimated that in 1990 the cancer incidence in Vietnam was about
      133 per 100 000 in males and 91.7 per 100 000 in females and that the mortality
      was 105.9 and 58.5 per 100 000, respectively (standardization to the world's
      population). In that year, Vietnam had at least 52 700 new cancer cases and 37
      700 dead from cancer. Although the National Cancer Control Program is still in
      preparation, some efforts by the government have already been made with tobacco
      control, improving the cancer treatment net, mass media education and production
      of vaccine against HBV. Cancer control in Vietnam still has to deal with
      challenges such as poor quality of cancer morbidity and mortality data, shortage
      of resources for establishing a comprehensive cancer control network from the
      center to the peripheries, lack of data for an anti-tobacco program and
      misunderstanding or limited knowledge of general practitioners and the public
      about the disease.

PMID- 11959883
TI  - COX-2 in cancer--a player that's defining the rules.

PMID- 11959884
TI  - Estrogen, tamoxifen, and the brain.

PMID- 11959885
TI  - On the eve of protein destruction: ubiquitin research begins to pay off.

PMID- 11959886
TI  - For proteomics research, a new race has begun.

PMID- 11959888
TI  - NIH seeks comment on proposed data sharing policy.

PMID- 11959889
TI  - Aerosolized chemotherapy? Inhalation therapy gains ground.

PMID- 11959890
TI  - Systematic review of psychological therapies for cancer patients: overview and
      recommendations for future research.
AB  - Many cancer patients use psychological therapies because they expect them to cure
      their cancer or to improve their recovery. Despite these high expectations, both
      patients and oncologists report being moderately to very satisfied with the
      results of psychological therapies. Previous reviews of the literature have
      concluded that psychological therapies may help cancer patients in various ways,
      ranging from reducing the side effects of cancer treatments to improving
      patients' immune function and longevity. However, because those reviews lacked
      methodologic rigor, we critically and systematically reviewed all identifiable
      publications about psychological therapies used by cancer patients to provide an
      objective and scientific evaluation of nontraditional therapies. We identified
      627 relevant papers that reported on 329 intervention trials by searching
      MEDLINE, Healthplan, Psychlit, and Allied and Complementary Medicine databases
      and in the bibliographies of the papers identified. Despite increased use of
      randomized, controlled trial designs over time, the methodologic quality of the
      intervention trials, on 10 internal validity indicators, was generally
      suboptimal, with only one trial achieving a quality rating of "good" for its
      methodology. Using effectiveness results from 34 trials with psychosocial
      outcomes, 28 trials with side effect outcomes, 10 trials with conditioned side
      effect outcomes, and 10 trials with survival or immune outcomes, we make only
      tentative recommendations about the effectiveness of psychological therapies for
      improving cancer patients' outcomes. Nevertheless, by exploring the relative
      effectiveness of the different intervention strategies for each outcome and
      follow-up period, we suggest the specific therapies that should be considered for
      further investigation. In addition, we suggest how future trials can maximize
      their internal validity by describing the minimal reporting standards that should
      be required in this field.

PMID- 11959891
TI  - Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced
      apoptosis in prostate cancer cells.
AB  - BACKGROUND: The antitumor activity of cyclooxygenase-2 (COX-2) inhibitors is
      thought to involve COX-2 enzyme inhibition and apoptosis induction, but it is
      unclear whether COX-2 inhibition is required for apoptosis. Different COX-2
      inhibitors have similar IC(50) values (concentration for 50% inhibition) for COX
      2 inhibition but differ considerably in their abilities to induce apoptosis,
      suggesting the involvement of a COX-2-independent pathway in apoptosis. To test
      this hypothesis, we investigated the effect of COX-2 depletion on apoptosis and
      performed a structure-activity analysis of the COX-2 inhibitor celecoxib in the
      androgen-independent prostate cancer cell line PC-3. METHODS: Tetracycline
      inducible (Tet-On) COX-2 antisense clones were isolated to assess the effect of
      COX-2 expression on cell viability and sensitivity to apoptosis induced by COX-2
      inhibitors. Untreated Tet-On clones differentially expressed COX-2, and
      doxycycline-treated clones were depleted of COX-2. We synthesized and
      characterized various celecoxib derivatives with various COX-2 inhibitory
      activities and determined their apoptotic activity in PC-3 cells. Apoptosis was
      assessed with four tests. RESULTS: In contrast to the effect of COX-2 inhibitors,
      which induced apoptosis, COX-2 depletion did not induce cell death.
      Susceptibility to COX-2 inhibitor-induced apoptosis was independent of the level
      of COX-2 expression. Structure-activity analysis found no correlation between
      apoptosis induction and COX-2 inhibition. Some celecoxib derivatives that lacked
      COX-2 inhibitory activity facilitated apoptosis and vice versa. Moreover,
      celecoxib and apoptosis-active celecoxib derivatives mediated cell death by
      inhibiting the same pathway. CONCLUSION: We have dissociated the apoptosis
      inducing activity from the COX-2 inhibitory activity by structural modifications
      of the COX-2 inhibitor celecoxib. This separation of activities may provide a
      molecular basis for the development of new classes of apoptosis-inducing agents.

PMID- 11959892
TI  - The effects of tamoxifen and estrogen on brain metabolism in elderly women.
AB  - BACKGROUND: Tamoxifen is used to treat breast cancer and may reduce the risk of
      breast cancer. However, there are conflicting reports as to whether tamoxifen use
      is associated with changes in brain metabolism and function or cognitive
      impairment. Consequently, we assessed the effects of tamoxifen and estrogen on
      the brain chemistry of elderly women. METHODS: We used proton magnetic resonance
      spectroscopy to measure the concentrations of N-acetyl-containing compounds, myo
      inositol (MI), total creatine (creatine plus phosphocreatine), and choline
      containing compounds in the frontal white matter, basal ganglia, and hippocampus
      of 76 elderly women of whom 16 had received tamoxifen therapy, 27 had received
      estrogen as hormone replacement therapy (HRT), and 33 had received neither
      (control group). A two-way analysis of variance (ANOVA) was performed to
      determine the statistical significance of differences in cerebral metabolite
      concentrations among subject groups and brain regions. All statistical tests were
      two-sided. RESULTS: Women in the tamoxifen and HRT groups had lower
      concentrations of MI in all areas than women in the control group (P =.02;
      overall group effect on ANOVA). Compared with the control group, the tamoxifen
      group (P =.004) and the HRT group (P =.06) had lower concentrations of MI in
      their basal ganglia. The MI concentration in the basal ganglia was inversely
      correlated with the duration of tamoxifen treatment (rho = -.72; P =.005).
      CONCLUSIONS: The reduced concentrations of MI in the brains of women treated with
      tamoxifen and HRT, compared with those of control women, suggest that tamoxifen
      has an effect similar to that of estrogen. These results, if confirmed, may
      alleviate concerns about the safety of using tamoxifen to reduce breast cancer
      risk in elderly women.

PMID- 11959893
TI  - Targeting urokinase-type plasminogen activator receptor on human glioblastoma
      tumors with diphtheria toxin fusion protein DTAT.
AB  - BACKGROUND: The prognosis for patients with brain cancer is poor, and new
      therapies are urgently needed. Recombinant toxic proteins that specifically
      target tumor cells appear to be promising. Urokinase-type plasminogen activator
      (uPA) receptor (uPAR) is expressed on the surface of glioblastoma and some other
      tumor cells and endothelial cells. We synthesized a recombinant fusion protein,
      DTAT, which contains the catalytic portion of diphtheria toxin (DT) for cell
      killing fused to the noninternalizing amino-terminal (AT) fragment of uPA, and
      investigated its effectiveness in targeting uPAR-positive tumor cells. METHODS:
      In vitro cytotoxicity of DTAT was measured by cell proliferation assays. For in
      vivo studies, athymic nude mice (four to five animals/group) bearing uPAR
      expressing human glioblastoma (U118MG) cell-induced tumors were injected with
      DTAT or control protein. Tumor volume was assessed over time, and differences
      between treatments were analyzed by Student's t test. Effects of DTAT on body
      organ systems were evaluated in normal, tumor-free C57BL/6 mice histologically
      and functionally by serum enzyme tests. All statistical tests were two-sided.
      RESULTS: In vitro, DTAT was highly potent and selective in killing uPAR
      expressing glioblastoma cells (U118MG, U373MG, and U87MG) and human umbilical
      vein endothelial cells. In vivo, compared with mice treated with control
      proteins, DTAT caused a statistically significant (P =.05) regression of small
      U118MG cell-induced tumors in all mice. Control fusion proteins that did not
      react with glioblastoma cells had no effect on tumor growth. DTAT given to tumor
      free C57BL/6 mice had little effect on kidney, liver, heart, lung, and spleen
      histologies. Serum analysis in the same mice showed no elevation in blood urea
      nitrogen, indicating lack of effect on kidney function but a statistically
      significant (P =.046), albeit non-life-threatening, elevation in liver alanine
      aminotransferase levels. CONCLUSION: DTAT may have potential for intracranial
      glioblastoma therapy because of its ability to target tumor cells and tumor
      vasculature simultaneously and its apparent lack of systemic effects.

PMID- 11959894
TI  - Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of
      nine prospective studies.
AB  - BACKGROUND: Reproductive and hormonal factors are involved in the etiology of
      breast cancer, but there are only a few prospective studies on endogenous sex
      hormone levels and breast cancer risk. We reanalyzed the worldwide data from
      prospective studies to examine the relationship between the levels of endogenous
      sex hormones and breast cancer risk in postmenopausal women. METHODS: We analyzed
      the individual data from nine prospective studies on 663 women who developed
      breast cancer and 1765 women who did not. None of the women was taking exogenous
      sex hormones when their blood was collected to determine hormone levels. The
      relative risks (RRs) for breast cancer associated with increasing hormone
      concentrations were estimated by conditional logistic regression on case-control
      sets matched within each study. Linear trends and heterogeneity of RRs were
      assessed by two-sided tests or chi-square tests, as appropriate. RESULTS: The
      risk for breast cancer increased statistically significantly with increasing
      concentrations of all sex hormones examined: total estradiol, free estradiol, non
      sex hormone-binding globulin (SHBG)-bound estradiol (which comprises free and
      albumin-bound estradiol), estrone, estrone sulfate, androstenedione,
      dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone. The RRs
      for women with increasing quintiles of estradiol concentrations, relative to the
      lowest quintile, were 1.42 (95% confidence interval [CI] = 1.04 to 1.95), 1.21
      (95% CI = 0.89 to 1.66), 1.80 (95% CI = 1.33 to 2.43), and 2.00 (95% CI = 1.47 to
      2.71; P(trend)<.001); the RRs for women with increasing quintiles of free
      estradiol were 1.38 (95% CI = 0.94 to 2.03), 1.84 (95% CI = 1.24 to 2.74), 2.24
      (95% CI = 1.53 to 3.27), and 2.58 (95% CI = 1.76 to 3.78; P(trend)<.001). The
      magnitudes of risk associated with the other estrogens and with the androgens
      were similar. SHBG was associated with a decrease in breast cancer risk (P(trend)
      =.041). The increases in risk associated with increased levels of all sex
      hormones remained after subjects who were diagnosed with breast cancer within 2
      years of blood collection were excluded from the analysis. CONCLUSION: Levels of
      endogenous sex hormones are strongly associated with breast cancer risk in
      postmenopausal women.

PMID- 11959895
TI  - Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and
      malignant human ovarian surface epithelial cells.
AB  - BACKGROUND: Reproductive hormones are associated with risk for epithelial ovarian
      cancer. To determine the effect of such hormones on the activation of interleukin
      6 (IL-6)/STAT3 (signal transducer and activator of transcription-3) signaling,
      which may be involved in ovarian cancer, we investigated the status of STAT3, IL
      6, and its receptor in immortalized human ovarian surface epithelial (HOSE) and
      ovarian cancer (OVCA) cell lines. METHODS: Two immortalized HOSE cell lines and
      two OVCA cell lines were cultured with gonadotropins, sex steroid hormones,
      and/or IL-6, alone or with specific inhibitors or IL-6-neutralizing antibodies.
      Expression of IL-6, the IL-6 receptor alpha chain (IL-6Ralpha), and
      phosphorylated and unphosphorylated STAT3 messenger RNAs (mRNAs) and proteins in
      all cells was determined. Cell proliferation and soft-agar colony formation were
      assessed. STAT3 activity was investigated in OVCA cells transfected with a
      dominant negative STAT3 (Dn-STAT3), wild-type STAT3, or an empty control vector.
      All statistical tests were two-sided. RESULTS: Levels of IL-6 mRNA and protein
      increased in all cells treated with follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), 17beta-estradiol, or estrone but increased only in OVCA
      cells treated with testosterone and 5alpha-dihydrotestosterone. For all lines, IL
      6 antibodies partially inhibited hormone-stimulated cell proliferation but
      completely inhibited IL-6-enhanced cell proliferation. IL-6 induced STAT3
      phosphorylation and activation in HOSE cells; STAT3 was constitutively activated
      in OVCA cells. Higher levels of IL-6Ralpha and STAT3 transcription factors were
      observed in OVCA cells than in HOSE cells. After transfection, Dn-STAT3
      suppressed endogenous STAT3 and inhibited all forms of IL-6-stimulated OVCA cell
      proliferation (OVCA 429 cells, P<.001; OVCA 432 cells, P<.006), whereas wild-type
      STAT3 enhanced HOSE cell proliferation (wild-type STAT3 at 0.5 microg/mL in HOSE
      306 cells, P<.002; STAT3 at 1.0 microg/mL in HOSE 306 or both concentrations of
      wild-type STAT3 in HOSE 642 cells, P<.001). CONCLUSIONS: The IL-6/STAT3 signaling
      pathway may mediate FSH-, LH-, and estrogen-stimulated HOSE cell proliferation.
      Increased IL-6Ralpha expression and constitutive STAT3 activation may be
      associated with ovarian cancer.

PMID- 11959896
TI  - Re: modification of clinical presentation of prostate tumors by a novel genetic
      variant in CYP3A4.

PMID- 11959898
TI  - Re: Helicobacter pylori seropositivity as a risk factor for pancreatic cancer.

PMID- 11959900
TI  - Genetic analysis of traditional and evolved Basmati and non-Basmati rice
      varieties by using fluorescence-based ISSR-PCR and SSR markers.
AB  - The objective of the present study was to make use of efficient molecular marker
      systems to reveal genetic relationships in traditional and evolved Basmati (EB)
      and semidwarf non-Basmati (NB) rice varieties. A subset of three rice groups was
      analyzed by using 19 simple sequence repeat (SSR) loci and 12 inter-SSR-PCR
      primers. A total of 70 SSR alleles and 481 inter-SSR-PCR markers were revealed in
      24 varieties from the three groups. The lowest genetic diversity was observed
      among the traditional Basmati varieties, whereas the EB varieties showed the
      highest genetic diversity by both the marker assays. The results indicated that
      the subset of aromatic rice varieties analyzed in the present study is probably
      derived from a single land race. The traditional Basmati (TB) and semidwarf NB
      rice varieties used in the present study were clearly delineated by both marker
      assays. A number of markers, which could unambiguously distinguish the TB
      varieties used in the present study from the evolved and NB rice varieties, were
      identified. The potential use of these markers in Basmati rice-breeding programs
      and authentication of TB varieties used in the present study are envisaged.

PMID- 11959901
TI  - A mutation that prevents paramutation in maize also reverses Mutator transposon
      methylation and silencing.
AB  - Both paramutation and Mutator (Mu) transposon inactivation involve heritable
      changes in gene expression without concomitant changes in DNA sequence. The
      mechanisms by which these shifts in gene activity are achieved are unknown. Here
      we present evidence that these two phenomena are linked mechanistically. We show
      that mutation of a gene, modifier of paramutation 1 (mop1), which prevents
      paramutation at three different loci in maize, can reverse methylation of Mutator
      elements reliably. In mop1 mutant backgrounds, methylation of nonautonomous Mu
      elements can be reversed even in the absence of the regulatory MuDR element.
      Previously silenced MuDR elements are reactivated sporadically after multiple
      generations of exposure to mop1 mutations. MuDR methylation is separable from
      MuDR silencing, because removal of methylation does not cause immediate
      reactivation. The mop1 mutation does not alter the methylation of certain other
      transposable elements including those just upstream of a paramutable b1 gene. Our
      results suggest that the mop1 gene acts on a subset of epigenetically regulated
      sequences in the maize genome and paramutation and Mu element methylation require
      a common factor, which we hypothesize influences chromatin structure.

PMID- 11959902
TI  - Pregnancy status and fetal prion genetics determine PrPSc accumulation in
      placentomes of scrapie-infected sheep.
AB  - Ovine scrapie is a fatal neurodegenerative disorder that may be transmitted
      through exposure to infected uterine and placental tissues. Susceptibility to
      scrapie is primarily controlled by polymorphisms in the prion protein (PrP) gene.
      Scrapie in the U.S. Suffolk breed and in many breeds in Europe occurs in sheep
      homozygous for glutamine (171QQ), but rarely in sheep heterozygous for glutamine
      and arginine (171QR) or homozygous for arginine (171RR) at codon 171 of the PrP
      gene. This study demonstrated that accumulation of PrP(Sc) in uterine-placental
      epithelial cells in the placentome was determined by fetal PrP genotype and the
      pregnancy status of scrapie-infected ewes. PrP(Sc) was detected in 171QQ
      placentomes of infected ewes, but not in placentomes of infected ewes pregnant
      with 171QR conceptuses or in the non-pregnant uterus of infected ewes. The
      distribution of PrP(Sc) plaques in placentomes was temporally associated with
      stage of gestation. There was a tendency toward increased size and number of
      placentomal PrP(Sc) plaques from the endometrial stalk (maternal side) to
      chorionic plate (fetal side). These results indicate that accumulation of PrP(Sc)
      is eliminated or reduced to undetectable levels in reproductive and placental
      tissues if infected ewes are not pregnant or conceive conceptuses with a
      resistant PrP genotype.

PMID- 11959903
TI  - Distinct roles for jasmonate synthesis and action in the systemic wound response
      of tomato.
AB  - Plant defense responses to wounding and herbivore attack are regulated by signal
      transduction pathways that operate both at the site of wounding and in undamaged
      distal leaves. Genetic analysis in tomato indicates that systemin and its
      precursor protein, prosystemin, are upstream components of a wound-induced,
      intercellular signaling pathway that involves both the biosynthesis and action of
      jasmonic acid (JA). To examine the role of JA in systemic signaling, reciprocal
      grafting experiments were used to analyze wound-induced expression of the
      proteinase inhibitor II gene in a JA biosynthetic mutant (spr-2) and a JA
      response mutant (jai-1). The results showed that spr-2 plants are defective in
      the production, but not recognition, of a graft-transmissible wound signal.
      Conversely, jai-1 plants are compromised in the recognition of this signal but
      not its production. It was also determined that a graft-transmissible signal
      produced in response to ectopic expression of prosystemin in rootstocks was
      recognized by spr-2 but not by jai-1 scions. Taken together, the results show
      that activation of the jasmonate biosynthetic pathway in response to wounding or
      (pro)systemin is required for the production of a long-distance signal whose
      recognition in distal leaves depends on jasmonate signaling. These findings
      suggest that JA, or a related compound derived from the octadecanoid pathway, may
      act as a transmissible wound signal.

PMID- 11959904
TI  - Functional correction of established central nervous system deficits in an animal
      model of lysosomal storage disease with feline immunodeficiency virus-based
      vectors.
AB  - Gene transfer vectors based on lentiviruses can transduce terminally
      differentiated cells in the brain; however, their ability to reverse established
      behavioral deficits in animal models of neurodegeneration has not previously been
      tested. When recombinant feline immunodeficiency virus (FIV)-based vectors
      expressing beta-glucuronidase were unilaterally injected into the striatum of
      adult beta-glucuronidase deficient [mucopolysaccharidosis type VII (MPS VII)]
      mice, an animal model of lysosomal storage disease, there was bihemispheric
      correction of the characteristic cellular pathology. Moreover, after the
      injection of FIV-based vectors expressing beta-glucuronidase into brains of beta
      glucuronidase-deficient mice with established impairments in spatial learning and
      memory, there was dramatic recovery of behavioral function. Cognitive improvement
      resulting from expression of beta-glucuronidase was associated with alteration in
      expression of genes associated with neuronal plasticity. These data suggest that
      enzyme replacement to the MPS VII central nervous system goes beyond restoration
      of beta-glucuronidase activity in the lysosome, and imparts improvements in
      plasticity and spatial learning.

PMID- 11959905
TI  - Glycine residues in potassium channel-like selectivity filters determine
      potassium selectivity in four-loop-per-subunit HKT transporters from plants.
AB  - Plant HKT proteins comprise a family of cation transporters together with
      prokaryotic KtrB, TrkH, and KdpA transporter subunits and fungal Trk proteins.
      These transporters contain four loop domains in one polypeptide with a proposed
      distant homology to K(+) channel selectivity filters. Functional expression in
      yeast and Xenopus oocytes revealed that wheat HKT1 mediates Na(+)-coupled K(+)
      transport. Arabidopsis AtHKT1, however, transports only Na(+) in eukaryotic
      expression systems. To understand the molecular basis of this difference we
      constructed a series of AtHKT1/HKT1 chimeras and introduced point mutations to
      AtHKT1 and wheat HKT1 at positions predicted to be critical for K(+) selectivity.
      A single-point mutation, Ser-68 to glycine, was sufficient to restore K(+)
      permeability to AtHKT1. The reverse mutation in HKT1, Gly-91 to serine, abrogated
      K(+) permeability. This glycine in P-loop A of AtHKT1 and HKT1 can be modeled as
      the first glycine of the K(+) channel selectivity filter GYG motif. The
      importance of such filter glycines for K(+) selectivity was confirmed by
      interconversion of Ser-88 and Gly-88 in the rice paralogues OsHKT1 and OsHKT2.
      Surprisingly, all HKT homologues known from dicots have a serine at the filter
      position in P-loop A, suggesting that these proteins function mainly as Na(+)
      transporters in plants and that Na(+)/K(+) symport in HKT proteins is associated
      with a glycine in the filter residue. These data provide experimental evidence
      that the glycine residues in selectivity filters of HKT proteins are structurally
      related to those of K(+) channels.

PMID- 11959906
TI  - Plasticity of orientation preference maps in the visual cortex of adult cats.
AB  - In contrast to the high degree of experience-dependent plasticity usually
      exhibited by cortical representational maps, a number of experiments performed in
      visual cortex suggest that the basic layout of orientation preference maps is
      only barely susceptible to activity-dependent modifications. In fact, most of
      what we know about activity-dependent plasticity in adults comes from experiments
      in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that
      has been proven highly effective in other cortical areas, we demonstrate here
      that enforced synchronous cortical activity induces major changes of orientation
      preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic
      signals and electrophysiological single-cell recordings, we show that a few hours
      of intracortical microstimulation (ICMS) lead to an enlargement of the cortical
      representational zone at the ICMS site and an extensive restructuring of the
      entire OPM layout up to several millimeters away, paralleled by dramatic changes
      of pinwheel numbers and locations. At the single-cell level, we found that the
      preferred orientation was shifted toward the orientation of the ICMS site over a
      region of up to 4 mm. Our results show that manipulating the synchronicity of
      cortical activity locally without invoking training, attention, or reinforcement,
      OPMs undergo large-scale reorganization reminiscent of plastic changes observed
      for nonvisual cortical maps. However, changes were much more widespread and
      enduring. Such large-scale restructuring of the visual cortical networks
      indicates a substantial capability for activity-dependent plasticity of adult
      visual cortex and may provide the basis for cognitive learning processes.

PMID- 11959907
TI  - Segmented nanofibers of spider dragline silk: atomic force microscopy and single
      molecule force spectroscopy.
AB  - Despite its remarkable materials properties, the structure of spider dragline
      silk has remained unsolved. Results from two probe microscopy techniques provide
      new insights into the structure of spider dragline silk. A soluble synthetic
      protein from dragline silk spontaneously forms nanofibers, as observed by atomic
      force microscopy. These nanofibers have a segmented substructure. The segment
      length and amino acid sequence are consistent with a slab-like shape for
      individual silk protein molecules. The height and width of nanofiber segments
      suggest a stacking pattern of slab-like molecules in each nanofiber segment. This
      stacking pattern produces nano-crystals in an amorphous matrix, as observed
      previously by NMR and x-ray diffraction of spider dragline silk. The possible
      importance of nanofiber formation to native silk production is discussed. Force
      spectra for single molecules of the silk protein demonstrate that this protein
      unfolds through a number of rupture events, indicating a modular substructure
      within single silk protein molecules. A minimal unfolding module size is
      estimated to be around 14 nm, which corresponds to the extended length of a
      single repeated module, 38 amino acids long. The structure of this spider silk
      protein is distinctly different from the structures of other proteins that have
      been analyzed by single-molecule force spectroscopy, and the force spectra show
      correspondingly novel features.

PMID- 11959908
TI  - Adaptive aberration correction in a confocal microscope.
AB  - The main advantage of confocal microscopes over their conventional counterparts
      is their ability to optically "section" thick specimens; the thin image slices
      thus obtained can be used to reconstruct three-dimensional images, a capability
      which is particularly useful in biological applications. However, it is well
      known that the resolution and optical sectioning ability can be severely degraded
      by system or specimen-induced aberrations. The use of high aperture lenses
      further exacerbates the problem. Moreover, aberrations can considerably reduce
      the number of photons that reach the detector, leading to lower contrast. It is
      rather unfortunate, therefore, that in practical microscopy, aberration-free
      confocal imaging is rarely achieved. Adaptive optics systems, which have been
      used widely to correct aberrations in astronomy, offer a solution here but also
      present new challenges. The optical system and the source of aberrations in a
      confocal microscope are considerably different and require a novel approach to
      wavefront sensing. This method, based upon direct measurement of Zernike
      aberration modes, also exhibits an axial selectivity similar to that of a
      confocal microscope. We demonstrate an adaptive confocal fluorescence microscope
      incorporating this modal sensor together with a deformable membrane mirror for
      aberration correction. Aberration corrected images of biological specimens show
      considerable improvement in contrast and apparent restoration of axial
      resolution.

PMID- 11959909
TI  - Molecular characterization of meiotic recombination across the 140-kb multigenic
      a1-sh2 interval of maize.
AB  - The 140-kb a1-sh2 interval of the maize genome contains at least four genes (a1,
      yz1, x1, and sh2). Partial sequence analysis of two haplotypes has revealed many
      single nucleotide polymorphisms and InDel polymorphisms, including several large
      structural polymorphisms. The physical positions of 101 meiotic recombination
      breakpoints are not distributed uniformly across the interval and are instead
      concentrated within three recombination hot spots. Two of these recombination hot
      spots are genic (a1 and yz1) and one is apparently nongenic. The x1 gene is not a
      recombination hot spot. Thus, these results suggest that not all hot spots are
      genes and indicate that not all genes are hot spots. Two of the 101 recombination
      events arose by means of either noncrossover events involving conversion tract
      lengths of at least 17 kb or double-crossover events. Only one recombination
      breakpoint mapped to the approximately 80-kb distal portion of the a1-sh2
      interval that contains large amounts of repetitive DNA including
      retrotransposons; in this region the ratio of genetic to physical distance is
      less than 0.5% of the genome's average. These results establish that the
      retrotransposon faction of the maize genome is relatively inert
      recombinationally.

PMID- 11959910
TI  - Allometric scaling and maximum efficiency in physiological eigen time.
AB  - General optimization results from physics indicate that maximum efficiency of a
      process, in the sense of minimum overall entropy production, is achieved when the
      rate of entropy production is constant over time, however not in ordinary clock
      time but on an, in general varying, "eigen time" scale, intrinsic to the system.
      We identify the eigen time of a biological system with "physiological time,"
      which generally scales with the 1/4 power of body mass, M(1/4), over a vast range
      of species. Since it is equally well established that metabolic rate scales as
      M(3/4), it follows that organisms produce entropy at the same intrinsic rate,
      fulfilling a necessary condition for maximum efficiency, and are all,
      furthermore, equally efficient on the physiological eigen time scale.

PMID- 11959911
TI  - Sustained stimulation shifts the mechanism of endocytosis from dynamin-1
      dependent rapid endocytosis to clathrin- and dynamin-2-mediated slow endocytosis
      in chromaffin cells.
AB  - Transient stimulation of secretion in calf chromaffin cells is invariably
      followed by rapid endocytosis (RE), a clathrin- and K(+)-independent process with
      a half time of several seconds. Here we show that when exocytosis is triggered in
      a more sustained manner, a much slower form of endocytosis (SE) replaces RE. SE
      is complete within 10 min and is abolished when anticlathrin antibodies are
      introduced into the cell or when intracellular K(+) is removed. RE, but not SE,
      is blocked by intracellular administration of antidynamin-1 antibodies; the
      inverse specificity was found for antidynamin-2 antibodies. Replacement of
      extracellular Ca(2+) by Ba(2+) or Sr(2+) completely blocked RE but had little
      effect on SE. Thus chromaffin cells exhibit two kinetically and mechanistically
      distinct forms of endocytosis that are coupled to different extents of exocytosis
      and are mediated by different isoforms of dynamin. We surmise that RE is
      associated with the transient fusion ("kiss-and-run") mechanism of transmitter
      release and is the prevalent means of vesicle recapture and recycling under
      normal physiological conditions, whereas the clathrin-based SE mechanism comes
      into play only at higher levels of stimulation and may be associated with
      complete fusion of vesicles with the plasma membrane.

PMID- 11959912
TI  - Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b
      receptor antagonist, SSR149415, suggest an innovative approach for the treatment
      of stress-related disorders.
AB  - The limbic localization of the arginine vasopressin V(1b) receptor has prompted
      speculation as to a potential role of this receptor in the control of emotional
      processes. To investigate this possibility, we have studied the behavioral
      effects of SSR149415, the first selective and orally active non-peptide
      antagonist of vasopressin V(1b) receptors, in a variety of classical (punished
      drinking, elevated plus-maze, and light/dark tests) and atypical (fear/anxiety
      defense test battery and social defeat-induced anxiety) rodent models of anxiety,
      and in two models of depression [forced swimming and chronic mild stress (CMS)].
      When tested in classical tests of anxiety, SSR149415 produced anxiolytic-like
      activity at doses that ranged from 1 to 30 mg/kg (i.p. or p.o.), but the
      magnitude of these effects was overall less than that of the benzodiazepine
      anxiolytic diazepam, which was used as a positive control. In contrast, SSR149415
      produced clear-cut anxiolytic-like activity in models involving traumatic stress
      exposure, such as the social defeat paradigm and the defense test battery (1-30
      mg/kg, p.o.). In the forced swimming test, SSR149415 (10-30 mg/kg, p.o.) produced
      antidepressant-like effects in both normal and hypophysectomized rats. Moreover,
      in the CMS model in mice, repeated administration of SSR149415 (10 and 30 mg/kg,
      i.p.) for 39 days improved the degradation of the physical state, anxiety,
      despair, and the loss of coping behavior produced by stress. These findings point
      to a role for vasopressin in the modulation of emotional processes via the V(1b)
      receptor, and suggest that its blockade may represent a novel avenue for the
      treatment of affective disorders.

PMID- 11959913
TI  - Truncated hemoglobin HbN protects Mycobacterium bovis from nitric oxide.
AB  - Mycobacterium tuberculosis, the causative agent of human tuberculosis, and
      Mycobacterium bovis each express two genes, glbN and glbO, encoding distantly
      related truncated hemoglobins (trHbs), trHbN and trHbO, respectively. Here we
      report that disruption of M. bovis bacillus Calmette-Guerin glbN caused a
      dramatic reduction in the NO-consuming activity of stationary phase cells, and
      that activity could be restored fully by complementing knockout cells with glbN.
      Aerobic respiration of knockout cells was inhibited markedly by NO in comparison
      to that of wild-type cells, indicating a protective function for trHbN. TyrB10,
      which is highly conserved in trHbs and interacts with the bound oxygen, was found
      essential for NO consumption. Titration of oxygenated trHbN (trHbN.O(2)) with NO
      resulted in stoichiometric oxidation of the protein with nitrate as the major
      product of the reaction. The second-order rate constant for the reaction between
      trHbN.O(2) and NO at 23 degrees C was 745 microM(-1).s(-1), demonstrating that
      trHbN detoxifies NO 20-fold more rapidly than myoglobin. These results establish
      a role for a trHb and demonstrate an NO-metabolizing activity in M. tuberculosis
      or M. bovis. trHbN thus might play an important role in persistence of
      mycobacterial infection by virtue of trHbN's ability to detoxify NO.

PMID- 11959914
TI  - Isoform-specific interaction of HP1 with human TAFII130.
AB  - The general transcription factor TFIID facilitates recruitment of the
      transcription machinery to gene promoters and regulates initiation of
      transcription by RNA polymerase II. hTAF(II)130, a component of TFIID, interacts
      with and serves as a coactivator for multiple transcriptional regulatory
      proteins, including Sp1 and CREB. A yeast two-hybrid screen has identified an
      interaction between hTAF(II)130 and heterochromatin protein 1 (HP1), a chromatin
      associated protein whose function has been implicated in gene silencing. We find
      that hTAF(II)130 associates with HP1 in an isoform-specific manner: HP1alpha and
      HP1gamma bind to hTAF(II)130, but not HP1beta. In addition, we show that
      endogenous hTAF(II)130 and components of TFIID in HeLa nuclear extracts associate
      with glutathione S-transferase-HP1alpha and -HP1gamma. hTAF(II)130 possesses a
      pentapeptide HP1-binding motif, and mutation of the hTAF(II)130 HP1 box
      compromises the interaction of hTAF(II)130 with HP1. We demonstrate that Gal4-HP1
      proteins interfere with hTAF(II)130-mediated activation of transcription. Our
      results suggest that HP1alpha and HP1gamma associate with hTAF(II)130 to mediate
      repression of transcription, supporting a new model of transcriptional repression
      involving a specific interaction between a component of TFIID and chromatin.

PMID- 11959915
TI  - Retroviral-mediated transmission of a mouse VL30 RNA to human melanoma cells
      promotes metastasis in an immunodeficient mouse model.
AB  - Infection of a human melanoma cell line by a retroviral vector resulted in
      transmission of a mouse VL30 (mVL30-1) retroelement RNA to some of the cells
      infected by the retrovirus, followed by synthesis, integration, and expression of
      the mVL30-1 cDNA. One vector carried a tissue factor (TF) transgene that
      generated high TF melanoma clones, and another vector was a control without the
      TF transgene that generated low TF clones. Some high TF melanoma clones contained
      the mVL30-1 retroelement and others did not, and some low TF melanoma clones
      contained the mVL30-1 retroelement and others did not. Each type of melanoma
      clone was tested for its metastatic potential in severe combined immunodeficient
      (SCID) mice, by i.v. injection of the cells to generate lung tumors. None of the
      low TF clones that either contained or lacked the mVL30-1 retroelement generated
      lung tumors, consistent with earlier results showing that high TF expression
      promoted metastasis. The high TF clones containing the mVL30-1 retroelement were
      strongly metastatic, in contrast to the high TF clones lacking the mVL30-1
      retroelement, which were weakly metastatic. Southern hybridization analyses
      showed that the mVL30-1 cDNA integrated into different genomic sites in different
      melanoma clones, suggesting that the effect of the mVL30-1 retroelement on
      metastasis depends not on integration per se but instead on expression of the
      mVL30-1 RNA. A role for the mVL30-1 RNA in metastasis and possibly other cell
      functions is an unexpected finding, because the RNA appears to lack significant
      coding potential for a functional protein. The metastatic effect might be
      mediated directly by a noncoding mVL30-1 RNA or by a peptide or small protein
      encoded by one of the short ORFs in the mVL30-1 RNA.

PMID- 11959916
TI  - Antigen challenge leads to in vivo activation and elimination of highly polarized
      TH1 memory T cells.
AB  - TH1 memory T cells derived from T cell receptor transgenic mice, in which the T
      cell antigen receptor is specific for a cytochrome C peptide in association with
      I-E(k), were transferred into normal B10.A mice and allowed to adopt a resting
      phenotype. When challenged, 30-60 days after transfer, with i.v. cytochrome C,
      the transgenic cells rapidly became activated, expressed mRNA for IFNgamma, and
      began to divide. However, after 48 h, the frequency of the cells fell
      progressively, reaching levels only slightly above the limit of detection by day
      8 and thereafter remain depressed for up to 90 days. The remaining cells were
      anergic as shown by limitation in proliferation and IFNgamma production in
      response to in vitro antigen stimulation. Even if challenged with antigen
      emulsified in complete Freund's adjuvant, the overall pattern was similar, except
      that in the draining lymph nodes, the surviving antigen-specific cells were not
      anergic, although spleen cells were still strikingly anergic. Thus, antigenic
      challenge of mice possessing resting memory TH1 CD4 T cells leads to the
      unanticipated loss of most of the specific cells and an apparent depletion rather
      than enhancement of immunologic memory.

PMID- 11959917
TI  - Lysosomal destabilization in p53-induced apoptosis.
AB  - The tumor suppressor wild-type p53 can induce apoptosis. M1-t-p53 myeloid
      leukemic cells have a temperature-sensitive p53 protein that changes its
      conformation to wild-type p53 after transfer from 37 degrees C to 32 degrees C.
      We have now found that these cells showed an early lysosomal rupture after
      transfer to 32 degrees C. Mitochondrial damage, including decreased membrane
      potential and release of cytochrome c, and the appearance of apoptotic cells
      occurred later. Lysosomal rupture, mitochondrial damage, and apoptosis were all
      inhibited by the cytokine IL-6. Some other compounds can also inhibit apoptosis
      induced by p53. The protease inhibitor N-tosyl-l-phenylalanine chloromethyl
      ketone inhibited the decrease in mitochondrial membrane potential and cytochrome
      c release, the Ca(2+)-ATPase inhibitor thapsigargin inhibited only cytochrome c
      release, and the antioxidant butylated hydroxyanisole inhibited only the decrease
      in mitochondrial membrane potential. In contrast to IL-6, these other compounds
      that inhibited some of the later occurring mitochondrial damage did not inhibit
      the earlier p53-induced lysosomal damage. The results indicate that apoptosis is
      induced by p53 through a lysosomal-mitochondrial pathway that is initiated by
      lysosomal destabilization, and that this pathway can be dissected by using
      different apoptosis inhibitors. These findings on the induction of p53-induced
      lysosomal destabilization can also help to formulate new therapies for diseases
      with apoptotic disorders.

PMID- 11959918
TI  - Ab initio protein structure prediction on a genomic scale: application to the
      Mycoplasma genitalium genome.
AB  - An ab initio protein structure prediction procedure, TOUCHSTONE, was applied to
      all 85 small proteins of the Mycoplasma genitalium genome. TOUCHSTONE is based on
      a Monte Carlo refinement of a lattice model of proteins, which uses threading
      based tertiary restraints. Such restraints are derived by extracting consensus
      contacts and local secondary structure from at least weakly scoring structures
      that, in some cases, can lack any global similarity to the sequence of interest.
      Selection of the native fold was done by using the convergence of the simulation
      from two different conformational search schemes and the lowest energy structure
      by a knowledge-based atomic-detailed potential. Among the 85 proteins, for 34
      proteins with significant threading hits, the template structures were reasonably
      well reproduced. Of the remaining 51 proteins, 29 proteins converged to five or
      fewer clusters. In the test set, 84.8% of the proteins that converged to five or
      fewer clusters had a correct fold among the clusters. If this statistic is simply
      applied, 24 proteins (84.8% of the 29 proteins) may have correct folds. Thus, the
      topology of a total of 58 proteins probably has been correctly predicted. Based
      on these results, ab initio protein structure prediction is becoming a practical
      approach.

PMID- 11959919
TI  - Tau is essential to beta -amyloid-induced neurotoxicity.
AB  - Senile plaques and neurofibrillary tangles, the two hallmark lesions of
      Alzheimer's disease, are the results of the pathological deposition of proteins
      normally present throughout the brain. Senile plaques are extracellular deposits
      of fibrillar beta-amyloid peptide (Abeta); neurofibrillary tangles represent
      intracellular bundles of self-assembled hyperphosphorylated tau proteins.
      Although these two lesions are often present in the same brain areas, a
      mechanistic link between them has yet to be established. In the present study, we
      analyzed whether tau plays a key role in fibrillar Abeta-induced neurite
      degeneration in central neurons. Cultured hippocampal neurons obtained from wild
      type, tau knockout, and human tau transgenic mice were treated with fibrillar
      Abeta. Morphological analysis indicated that neurons expressing either mouse or
      human tau proteins degenerated in the presence of Abeta. On the other hand, tau
      depleted neurons showed no signs of degeneration in the presence of Abeta. These
      results provide direct evidence supporting a key role for tau in the mechanisms
      leading to Abeta-induced neurodegeneration in the central nervous system. In
      addition, the analysis of the composition of the cytoskeleton of tau-depleted
      neurons suggested that the formation of more dynamic microtubules might confer
      resistance to Abeta-mediated neurodegeneration.

PMID- 11959921
TI  - Genetic complementation in apicomplexan parasites.
AB  - A robust forward genetic model for Apicomplexa could greatly enhance functional
      analysis of genes in these important protozoan pathogens. We have developed and
      successfully tested a genetic complementation strategy based on genomic insertion
      in Toxoplasma gondii. Adapting recombination cloning to genomic DNA, we show that
      complementing sequences can be shuttled between parasite genome and bacterial
      plasmid, providing an efficient tool for the recovery and functional assessment
      of candidate genes. We show complementation, gene cloning, and biological
      verification with a mutant parasite lacking hypoxanthine-xanthine-guanine
      phosphoribosyltransferase and a T. gondii cDNA library. We also explored the
      utility of this approach to clone genes based on function from other apicomplexan
      parasites using Toxoplasma as a surrogate. A heterologous library containing
      Cryptosporidium parvum genomic DNA was generated, and we identified a C. parvum
      gene coding for inosine 5-monophosphate-dehydrogenase (IMPDH). Interestingly,
      phylogenetic analysis demonstrates a clear eubacterial origin of this gene and
      strongly suggests its lateral transfer from epsilon-proteobacteria. The
      prokaryotic origin of this enzyme might make it a promising target for
      therapeutics directed against Cryptosporidium.

PMID- 11959922
TI  - Kinesin-microtubule binding depends on both nucleotide state and loading
      direction.
AB  - Kinesin is a motor protein that transports organelles along a microtubule toward
      its plus end by using the energy of ATP hydrolysis. To clarify the nucleotide
      dependent binding mode, we measured the unbinding force for one-headed kinesin
      heterodimers in addition to conventional two-headed kinesin homodimers under
      several nucleotide states. We found that both a weak and a strong binding state
      exist in each head of kinesin corresponding to a small and a large unbinding
      force, respectively; that is, weak for the ADP state and strong for the
      nucleotide-free and adenosine 5'-[beta,gamma-imido]triphosphate states. Model
      analysis showed that (i) the two binding modes in each head could be explained by
      a difference in the binding energy and (ii) the directional instability of
      binding, i.e., dependence of unbinding force on loading direction, could be
      explained by a difference in the characteristic distance for the kinesin
      microtubule interaction during plus- and minus-end-directed loading. Both these
      factors must play an important role in the molecular mechanism of kinesin
      motility.

PMID- 11959924
TI  - Evolution of supercolonies: the Argentine ants of southern Europe.
AB  - Some ants have an extraordinary social organization, called unicoloniality,
      whereby individuals mix freely among physically separated nests. This type of
      social organization is not only a key attribute responsible for the ecological
      domination of these ants, but also an evolutionary paradox and a potential
      problem for kin selection theory because relatedness between nest mates is
      effectively zero. The introduction of the Argentine ant in Europe was apparently
      accompanied by a dramatic loss of inter-nest aggression and the formation of two
      immense supercolonies (which effectively are two unicolonial populations).
      Introduced populations experienced only limited loss of genetic diversity at
      neutral markers, indicating that the breakdown of recognition ability is unlikely
      to be merely due to a genetic bottleneck. Rather, we suggest that a "genetic
      cleansing" of recognition cues occurred after introduction. Indeed workers of the
      same supercolony are never aggressive to each other despite the large
      geographical distance and considerable genetic differentiation between sampling
      sites. By contrast, aggression is invariably extremely high between the two
      supercolonies, indicating that they have become fixed for different recognition
      alleles. The main supercolony, which ranges over 6,000 km from Italy to the
      Spanish Atlantic coast, effectively forms the largest cooperative unit ever
      recorded.

PMID- 11959923
TI  - Decreased expression of the transcription factor NURR1 in dopamine neurons of
      cocaine abusers.
AB  - Chronic exposure to cocaine induces long-term adaptations that are likely to
      involve changes in transcription factor expression. This possibility has not been
      examined in the cocaine-exposed human brain. The transcription factor nurr1 is
      highly expressed in rodent midbrain dopamine neurons and is essential for their
      proper phenotypic development. Here we show that human NURR1 gene expression is
      robust within control subjects and reduced markedly within the dopamine neurons
      of human cocaine abusers. NURR1 is known to regulate transcription of the gene
      encoding the cocaine-sensitive dopamine transporter (DAT). We show here that DAT
      gene expression also is reduced markedly in the dopamine neurons of NURR1
      deficient cocaine abusers, suggesting that NURR1 plays a critical role in vivo in
      controlling human DAT gene expression and adaptation to repeated exposure to
      cocaine.

PMID- 11959925
TI  - A compelling genetic hypothesis for a complex disease: PRODH2/DGCR6 variation
      leads to schizophrenia susceptibility.

PMID- 11959926
TI  - Yeast weighs in on the elusive spindle matrix: New filaments in the nucleus.

PMID- 11959927
TI  - The past as the key to the present: resurrection of ancient proteins from
      eosinophils.

PMID- 11959929
TI  - Beyond molecules: self-assembly of mesoscopic and macroscopic components.
AB  - Self-assembly is a process in which components, either separate or linked,
      spontaneously form ordered aggregates. Self-assembly can occur with components
      having sizes from the molecular to the macroscopic, provided that appropriate
      conditions are met. Although much of the work in self-assembly has focused on
      molecular components, many of the most interesting applications of self
      assembling processes can be found at larger sizes (nanometers to micrometers).
      These larger systems also offer a level of control over the characteristics of
      the components and over the interactions among them that makes fundamental
      investigations especially tractable.

PMID- 11959930
TI  - Dendrimers and supramolecular chemistry.

PMID- 11959931
TI  - Two-dimensional supramolecular chemistry with molecular Tinkertoys.

PMID- 11959932
TI  - Supramolecular chemistry and self-assembly.
AB  - Supramolecular systems--their successes, problems, and potential--are discussed
      with allusion to specific examples.

PMID- 11959933
TI  - Supramolecular recognition: on the kinetic lability of thermodynamically stable
      host-guest association complexes.
AB  - A molecular receptor consisting of a spacer bearing two cofacially disposed
      terpyridyl-palladium-ligand (terpy-Pd-L) units rigidly separated by about 7 A has
      been investigated for molecular recognition of planar aromatic molecules. It is
      found that although the receptor forms stable 1:2 host-guest association
      complexes with 9-methylanthracene (9-MA), the guest undergoes very rapid site
      exchange within the receptor and with external free 9-MA. A crystal structure of
      the 2:1 adduct shows one 9-MA in the molecular cleft defined by the two terpy-Pd
      L units and the other resides on an outside face of one terpy-Pd-L unit. To
      establish the site residency time of the guests, a number of tethered molecules
      were prepared. These involve an anthracene molecule tethered to a pyridine ligand
      bound to the palladium atoms to form intramolecular host-guest adducts. Rotating
      frame Overhauser effects were used to infer the site residency of the anthracene
      guests in the receptor. Variable-temperature (1)H NMR spectroscopy of the
      intramolecular host-guest complexes has revealed that the site residency time of
      the anthracene guests is 1.6 x 10(-5) sec at 20 degrees C and 1.3 sec at -90
      degrees C in acetone solution. Whereas the guests are thermodynamically stable,
      they are kinetically very labile. A crystal structure of one of the tethered host
      guest adducts reveals the expected structure which is the same as that determined
      in solution by (1)H rotating-frame Overhauser enhancement spectroscopy
      experiments.

PMID- 11959934
TI  - Factors affecting the threading of axle molecules through macrocycles: binding
      constants for semirotaxane formation.
AB  - The threading of more or less linear axle molecules through macrocyclic
      molecules, a fundamental process relating to the formation of interlocked
      molecular structures, has been investigated through the study in acetone of the
      equilibrium constants for the formation of pseudorotaxanes by NMR methods. The 30
      new axle molecules have in common a secondary ammonium group, present as the
      thiocyanate salt, and an anthracen-9-ylmethyl group, but are rendered unique by
      the second amine substituent. All rotaxanes involve the well known polyether
      macrocycle, benzo[24]crown-8. The constants for the binding of axles having
      linear groups ranging from 2 to 18 carbon atoms show little variation in binding
      constant but are divided into two groups by their equilibration rates. Those with
      less than five methylene groups react rapidly on the NMR timescale, whereas those
      having more than five methylene groups are slow. Branching inhibits binding, but
      the effect decreases as the branch is moved away from the amine. Phenyl groups
      weaken binding when close to the amine but strengthen binding when more remote.
      Some functional groups decrease pseudorotaxane stability (alcohol functions),
      whereas others increase binding (carboxylic acid groups).

PMID- 11959935
TI  - Biomimetic macrocyclic receptors for carboxylate anion recognition based on C
      linked peptidocalix[4]arenes.
AB  - Two neutral macrobicyclic anion receptors 4 and 6, containing a calix[4]arene in
      the cone conformation, two l-alanine units, and a 2,6-diacylpyridine or a
      phthaloyl bridge, are described. The x-ray crystal structure of the acetone
      complexes of the pyridine containing macrocycle 6 shows the four amide NH groups
      to be in close proximity to the chiral pocket delimited by the pyridine and one
      aromatic nucleus of the calix[4]arene. This conformation is also the most stable
      in acetone-d6 solution, as proven by one- and two-dimensional NMR spectral
      measurements. Electrospray ionization-MS and (1)H NMR experiments reveal that the
      two ligands strongly bind carboxylate anions in acetone solution. H-bonding
      interactions between the carboxylate anions and the amide NH groups, together
      with pi/pi stacking, are invoked to explain the efficiency and the selectivity of
      these anion receptors.

PMID- 11959936
TI  - Guest-induced organization of an optimal receptor from a dynamic receptor
      library: spectroscopic screening.
AB  - Complexation of a cis-protected palladium ion and a family of exo-bidentate and 
      tridentate ligands results in the formation of an equilibrium mixture of numerous
      metal-linked receptors that are referred to as a dynamic receptor library. We
      found that a guest induced the selective formation of the optimal receptor of its
      own. Screening of the library by using difference NMR facilitates the search for
      new receptors because in difference NMR only receptors interacting with the guest
      can be observed. An unpredictable heterotopic receptor was discovered by this
      screening method. Interestingly, the new receptor thus found was assembled
      quantitatively only in the presence of its optimal guest.

PMID- 11959937
TI  - Adjusting the binding thermodynamics, kinetics, and orientation of guests within
      large synthetic hydrophobic pockets.
AB  - Kinetic analysis of the host guest complexation of a large, open molecular basket
      and a highly complementary adamantoid guest reveals that for these types of
      systems a dissociative mechanism is in operation. Hence, the resident adamantyl
      guest must completely vacate the cavity before another guest molecule can move in
      to replace it. As a result of the rigid nature of the host, the energy barrier to
      this process is relatively high, about 16 kcal mol(-1) at room temperature.
      Modifying the cavity of the host by dangling either a methyl group or a hydroxyl
      group from the portal rim alters the thermodynamic binding profile of these
      hosts. (1)H NMR shift data analysis also reveals that these functional groups can
      adjust the orientation that monosubstituted guests adopt within the cavity.
      Additionally, (1)H NMR studies of the binding of (E)1,4-dibromoadamantane allow
      the observation of two energetically similar diastereomeric complexes. An
      examination of this guest binding to the three hosts reveals that the interchange
      between the isomers is much faster than the entry and egression rates, and that
      the functional groups at the rim of each cavity influence both the rates of
      reorientation and the equilibrium relating the isomers.

PMID- 11959938
TI  - "Size-selectivity" in the template-directed assembly of dinuclear triple-stranded
      helicates.
AB  - The self-assembly of supramolecular structures depends on a subtle interplay of a
      series of different control mechanisms. The geometric as well as electronic
      complementarity of the molecular building blocks is crucial for the specific
      formation of defined supramolecular species. In addition, secondary effects, like
      templating, also have an important function. The templating ability of different
      cations in the formation of triple-stranded helicate-type complexes from alkyl
      bridged di(8-hydroxyquinoline) ligands is investigated by introduction of alkyl
      chains of different length as ligand spacers. Hereby a "size-selectivity" between
      the cations and the dinuclear helicate-type complexes [(ligand)(3)M(2)] is
      observed. Large cations support the formation of big dinuclear complexes, whereas
      small cations are able to template the formation of small complexes.

PMID- 11959939
TI  - Substituent effects on cation-pi interactions: a quantitative study.
AB  - A synthetic supramolecular complex has been adapted to quantify cation-pi
      interactions in chloroform by using chemical double-mutant cycles. The
      interaction of a pyridinium cation with the pi-face of an aromatic ring is found
      to be very sensitive to the pi-electron density. Electron-donating substituents
      lead to a strong attractive interaction (-8 kJ/mol(-1)), but electron-withdrawing
      groups lead to a repulsive interaction (+2 kJ/mol(-1)).

PMID- 11959940
TI  - Systematic assembly of the double molecular boxes: [Cs subset
      [CpCo(CN)(3)](4)[Cp*Ru](3)] as a tridentate ligand.
AB  - Cubic cage compounds composed of Co-CN-Ru linkages have been prepared which
      illustrate the following features: (i) new motifs for alkali metal ion
      complexation (i.e., cationic receptors for cations), (ii) a new family of triaza
      metalloligands, and (iii) a double box-like cage. The cages are synthesized by
      the condensation of [CpCo(CN)(3)](-) and [Cp*Ru(NCMe)(3)](+) (cyclopentadienyl,
      Cp; pentamethylcyclopentadienyl, Cp*) the presence of Cs(+). The species [Cs
      subset[[CpCo(CN)(3)](4)[Cp*Ru](4)](+) and [Cs
      subset[[CpCo(CN)(3)](4)[Cp*Ru](3)[Cp*Rh]](2+) illustrate the box-completion
      reaction Cs subset Co(4)Ru(3) + M (M = Cp*Rh(2+), Cp*Ru(+)). With the naked ion
      precursors [Na(NCMe)(6)](+) and [Fe(NCMe)(6)](2+), the box-completion reactions
      afforded [Na[Cs subset[CpCo(CN)(3)](4)[Cp*Ru](3)]](2)](+) and [Fe[Cs subset
      [CpCo(CN)(3)](4)[Cp*Ru](3)]](2)](2+). These cages provide the first examples, to
      our knowledge, of the double-box motif.

PMID- 11959941
TI  - New supramolecular trigonal prisms from zinc(II)- 1,4,7,10-tetraazacyclododecane
      (cyclen) complexes and trithiocyanurate in aqueous solution.
AB  - The multiple bonding between multinuclear zinc(II)-1,4,7,10-tetraazacyclododecane
      (cyclen, a 12-membered tetraamine) complexes and multidentate ligands is an
      effective method for constructing supramolecular complexes having well defined
      and distinct structures in aqueous solution. Herein we present examples of
      supramolecular D(3h) prisms formed by self-assembly of linearly dimeric or
      trimeric zinc(II)-cyclen complexes with a potentially trianionic C(3) subunit
      trithiocyanuric acid (TCA(3-)), wherein Zn(2+)-S(-) or Zn(2+)-N(-) coordination
      bonds and hydrogen bonds are responsible for stability of the multicomponent
      architectures in aqueous solution at neutral pH.

PMID- 11959942
TI  - Geometric requirements and examples of important structures in the assembly of
      square building blocks.
AB  - The basic structures for linking squares into polyhedra and networks
      (reticulation) are enumerated, and corresponding examples are described in which
      crystals were synthesized by linking paddle wheel (square) units into metal
      organic frameworks (MOFs)--named MOF-102 to MOF-112.

PMID- 11959943
TI  - Using multimodal ligands to influence network topology in silver(I) coordination
      polymers.
AB  - A range of Ag(I) one- and two-dimensional coordination frameworks has been
      prepared and structurally characterized by using the multimodal ligand 3,6-di
      pyrazin-2-yl-(1,2,4,5)-tetrazine, which offers both monodentate and chelating
      binding sites. It is demonstrated that multimodal ligands can be used to prepare
      coordination frameworks with novel and unusual topologies and to influence the
      precise geometrical arrangement of both ligands and metal centers within such
      supramolecular arrays.

PMID- 11959944
TI  - Cluster self-assembly of di[gold(I)]halonium cations.
AB  - Treatment of gold(I) halide complexes of the type L-Au-X [where L = PPh(3),
      PEt(3) with X = Cl, Br, I, or L = 2,6-(MeO)(2)C(6)H(3)PPh(2) with X = Cl] with
      AgSbF(6) in the molar ratio 2:1 in dichloromethane/tetrahydrofuran at -78 degrees
      C affords high yields of di[gold(I)]halonium salts of the formula
      [X[Au(PR(3))](2)](+) SbF(6)(-) (2-8). A determination of the crystal structures
      of the four triarylphosphine complexes (2-4, 8) revealed the presence of novel
      tetranuclear dications with a highly symmetrical structure (point group S(4))
      that arises from self-assembly of the dinuclear monocations through a set of four
      equivalent aurophilic Au-Au interactions. A comparison with two reference
      structures of corresponding chloronium perchlorate and bromonium
      tetrafluoroborate salts with monomeric, dinuclear cations shows that the geometry
      of the latter is greatly altered on dimerization to optimize the interactions
      between the closed-shell metal centers (Au: 5d(10)). Weak metallophilic bonding
      clearly becomes significant only in crystal lattices where anions with a larger
      ionic radius (SbF(6)(-) vs. BF(4)(-), ClO(4)(-)) reduce the otherwise dominant
      role of strong interionic Coulomb forces. The results indicate that aurophilic
      bonding is indeed an ubiquitous, quite dependable mode of intermetallic
      interactions provided that the right environment is chosen to allow the weak
      forces to become operative.

PMID- 11959945
TI  - Biomimetic self-assembly of a functional asymmetrical electronic device.
AB  - This paper introduces a biomimetic strategy for the fabrication of asymmetrical,
      three-dimensional electronic devices modeled on the folding of a chain of
      polypeptide structural motifs into a globular protein. Millimeter-size polyhedra
      patterned with logic devices, wires, and solder dots-were connected in a linear
      string by using flexible wire. On self-assembly, the string folded spontaneously
      into two domains: one functioned as a ring oscillator, and the other one as a
      shift register. This example demonstrates that biomimetic principles of design
      and self-organization can be applied to generate multifunctional electronic
      systems of complex, three-dimensional architecture.

PMID- 11959946
TI  - Hydrogen bonding and perhalometallate ions: a supramolecular synthetic strategy
      for new inorganic materials.
AB  - A synthetic strategy for constructing ionic hydrogen-bonded materials by
      combining perhalometallate anions with cations able to serve as hydrogen bond
      donors is presented. The approach is based on identification of well defined
      hydrogen bond acceptor sites on the anions by a combination of experimental and
      theoretical approaches. Selective population of these sites by hydrogen bond
      donors has the potential to afford organized crystalline arrays in one, two, or
      three dimensions. The approach is applicable to a wide range of metal centers.

PMID- 11959947
TI  - Resorcinarenes with 2-benzimidazolone bridges: self-aggregation, self-assembled
      dimeric capsules, and guest encapsulation.
AB  - The synthesis and spectroscopic characterization of self-assembled dimeric
      resorcinarenes 1a-d containing four 2-benzimidazolone (cyclic urea) bridges are
      reported. The nanometer-size capsules are held together by a cyclic array of
      complementary hydrogen bonds. Unlike the related imide-bridged resorcinarenes
      reported by Rebek and coworkers [Heinz, T., Rudkevich, D. M. & Rebek, J., Jr.
      (1998) Nature (London) 394, 764-766], these strongly bound dimers aggregate in
      chloroform solutions yielding different self-organized structures, depending on
      the nature and length of the four carbon chains attached at the bottom of each
      resorcinarene platform, as revealed by transmission electron microscopy. Thus,
      phenethyl groups (dimer 1c x 1c) produce long fibers, probably arising from tail
      to tail contacts and subsequent threading of the resulting linear self-assembled
      polymers, whereas long alkyl chains (dimers 1a x 1a and 1b x 1b) induce formation
      of large reverse vesicles of 0.8-2.2 microm diameter through side to side
      extensive stacking. Presumably, the rigidity of the dimer precludes folding of
      the aggregate into smaller vesicles. On the contrary, dimer 1d. 1d, containing
      four nine-carbon chains and a cis-double bond, does not substantially aggregate
      and gives rise to reasonably resolved (1)H NMR spectra. The compound was shown to
      be dimeric either by matrix-assisted laser desorption ionization-time-of-flight
      and vapor pressure osmometry. Encapsulation studies were followed by NMR.
      Propionic or pivalic acid was included in the capsules, probably as head to head
      hydrogen-bonded dimers in mesitylene-d(12), a solvent too big to be a guest by
      its own. Longer dimeric carboxylic acids or larger substrates, like 2-adamantyl
      azide or cyclohexylcarbodiimide, do not encapsulate, but mixtures of a long and a
      short carboxylic acid (i.e., propionic-adamantyl or propionic-cyclohexyl) yield
      pairwise complexes.

PMID- 11959948
TI  - From reactants to products via simple hydrogen-bonding networks: Information
      transmission in chemical reactions.
AB  - The transmission of information is ubiquitous in nature and often occurs through
      supramolecular hydrogen bonding processes. Here we report that there is a
      remarkable correlation during synthesis between the efficiency of the hydrogen
      bond-directed assembly of peptide-based [2]rotaxanes and the symmetry distortion
      of the macrocycle in the structure of the final product. It transpires that the
      ability of the flexible macrocycle-precursor to wrap around an unsymmetrical
      hydrogen bonding template affects both the reaction yield and a quantifiable
      measure of the symmetry distortion of the macrocycle in the product. When the
      yields of peptide rotaxane-forming reactions are high, so is the symmetry
      distortion in the macrocycle; when the yields are low, indicating a poor fit
      between the components, the macrocycle symmetry is relatively unaffected by the
      thread. Thus during a synthetic sequence, as in complex biological assembly
      processes, hydrogen bonding can code and transmit "information"--in this case a
      distortion from symmetry--between chemical entities by means of a
      supramolecularly driven multicomponent assembly process. If this phenomenon is
      general, it could have far reaching consequences for the use of supramolecular
      directed reactions in organic chemistry.

PMID- 11959949
TI  - Circular dichroism readout of sugar recognition in the cleft of a fused-pyridine
      receptor.
AB  - Dicarboxamide host 2 forms 1:1 complexes with n-octyl pyranosides derived from D
      glucose, D-mannose, D-galactose, D-fucose, D-lyxose, and D-arabinose. Association
      constants (K(a)) in the range of 77-940 M(-1) were measured in chloroform by
      means of induced circular dichroism and fluorescence spectroscopy. Variations in
      K(a) values correspond qualitatively to expected differences in hydrogen-bonding
      abilities of guest hydroxyl groups. Induced circular dichroism effects for
      complexes of saccharides bearing equatorial 3-OH, 4-OH, and 6-OH groups show that
      the host chromophore is twisted in a P-helical conformation. A structural model
      is proposed that is also consistent with the results of previous studies
      involving complexation of dicarboxylic acid 1 with cationic saccharides in
      methanol.

PMID- 11959950
TI  - Hydrogen bond-directed aggregation of diazadibenzoperylene dyes in low-polarity
      solvents and the solid state.
AB  - The formation of complex superstructures via hydrogen bonding of two ditopic
      building blocks, diazadibenzoperylenes 1a,b and isophthalic acid 2, has been
      investigated. It was found that only the phenoxy-substituted diazadibenzoperylene
      1a forms extended assemblies with 2 in complexes of a 1:1 stoichiometry, whereas
      for the 4-tert-butylphenoxy-substituted analogue 1b, no indications for
      superstructure formation with 2 were found. The different behavior is explained
      by the presence of additional pi-pi interactions, which are only observed for [1a
      x 2], as revealed by concentration-dependent optical absorption and fluorescence
      spectroscopy. Based on variable temperature x-ray diffraction studies, a lamellar
      structure for [1a x 2] is proposed that takes into account the concept of
      microphase-segregation.

PMID- 11959951
TI  - A self-assembled, redox-responsive receptor for the selective extraction of LiCl
      from water.
AB  - There is considerable interest in synthetic ionophores with high affinity and
      selectivity for Li(+). But so far, compounds that selectively bind Li(+) in the
      presence of other alkali and alkaline earth metal ions are rare and current
      approaches toward this goal are often accompanied with substantial synthetic
      efforts. Here we describe a trinuclear ruthenium metallamacrocyclic complex (1)
      that was obtained by self-assembly of ruthenium halfsandwich complexes and 3
      hydroxy-2-pyridone ligands. This complex was shown to be an extremely potent
      receptor for LiCl with an affinity high enough to extract LiCl from water. The
      selectivity of this receptor is exceptional: even in the presence of a large
      excess of Na(+), K(+), Cs(+), Ca(2+), and Mg(2+), Li(+) was extracted
      exclusively. The Li(+)/Na(+) selectivity ratio was determined to be higher than
      1,000:1. Compared with other synthetic ionophores, the receptor 1 offers two
      additional advantages: (i) the synthesis can be accomplished in one step by using
      simple starting materials; and (ii) the presence of lithium ions can be detected
      electrochemically. Complex 1 is therefore a very attractive candidate for the
      construction of a Li(+)-specific chemosensor.

PMID- 11959952
TI  - Self-assembly of a metal-ion-bound monolayer of trigonal connectors on mercury:
      an electrochemical Langmuir trough.
AB  - The adsorption of the trigonal connector, 1,3,5-tris[10-(3
      ethylthiopropyl)dimethylsilyl-1,10-dicarba-closo-decaboran-1-yl]benzene (1), from
      acetonitrile/0.1 M LiClO(4) on the surface of mercury at potentials ranging from
      +0.3 to -1.4 V (vs. aqueous Ag/AgCl/1 M LiCl) was examined by voltammetry,
      Langmuir isotherms at controlled potentials, and impedance measurements. No
      adsorption is observed at potentials more negative than approximately -0.85 V.
      Physisorption is seen between approximately -0.85 and 0 V. At positive
      potentials, adsorbate-assisted anodic dissolution of mercury occurs and an
      organized surface layer is formed. Although the mercury cations are reduced at 
      0.10 V, the surface layer remains metastable to potentials as negative as -0.85
      V. Its surface areas per molecule and per redox center are compatible with a
      regular structure with the connectors 1 woven into a hexagonal network by RR'S-
      >Hg(2)(2+)<--SRR' or RR'S-->Hg(2+)<--SRR' bridges. The structure is simulated
      closely by geometry optimization in the semiempirical AM1 approximation.

PMID- 11959953
TI  - Formation of oriented molecular nanowires on mica surface.
AB  - Molecular "nanowire" structures composed of the charge transfer complex of a bis
      tetrathiafulvalene substituted macrocycle and tetrafluorotetracyanoquinodimethane
      were constructed on mica substrates by employing the Langmuir-Blodgett technique.
      The nanowires transferred from a dilute aqueous potassium chloride subphase had
      typical dimensions of 2.5 nm x 50 nm x 1 microm. The nanowires are oriented to
      specific directions, corresponding to the directions of the potassium-ion array
      on the mica surface having sixfold symmetry. Such correlation between the
      nanowires and the substrate surface was also observed when a dilute aqueous
      rubidium chloride subphase was used. On the other hand, the correlation
      completely disappeared when the subphase contained divalent cations, indicating
      that the molecular nanowires orient by recognizing the monocation array on the
      mica surface. The nanowires formed by the vertical dipping method coexist with
      the monolayers. Only nanowire structures are, however, observed when we apply the
      horizontal lifting method. Based on the crystal structure of a related complex, a
      possible structure of the nanowires is presented. The conductivity of the
      nanowires was estimated to be of the order of 10(-3) S x cm(-1). The nanowires
      formed specific (regular) structures such as T-shape junctions, suggesting their
      use in construction of future molecular nanoscale devices.

PMID- 11959954
TI  - Colloidal assemblies on patterned silane layers.
AB  - The site-selective assembly of colloidal polymer particles onto laterally
      patterned silane layers was studied as a model system for the object assembly
      process at mesoscale dimensions. The structured silane monolayers on silicon
      oxide substrates were fabricated by a combination of liquid- and gas-phase
      deposition of different trialkoxysilanes with a photolithographic patterning
      technique. By using this method various types of surface functionalizations such
      as regions with amino functions next to areas of the bare silica surface or
      positively charged regions of a quaternary ammonium silane surrounded by a
      hydrophobic octadecylsilane film could be obtained. Furthermore, a
      triethoxysilane with a photoprotected amino group was synthesized, which allowed
      direct photopatterning after monolayer preparation, leading to free NH(2) groups
      at the irradiated regions. The different silane monolayer patterns were used to
      study the surface assembly behavior of carboxylated methacrylate particles by
      optical and scanning electron microscopy. In dependence of the assembly
      conditions (different surface functionalizations, pH, and drying conditions), a
      selective preference of the particles for a specific surface type versus others
      was found. Site-specific colloid adsorption could be observed also on the
      photosensitive silane layers after local deprotection with light. From the
      photosensitive silane and positively charged ammonium silane, molecularly mixed
      monolayers were prepared, which allowed particle adsorption and photoactivation
      within the same monolayer as shown by fluorescence labeling.

PMID- 11959955
TI  - Metal ion recognition and molecular templating in self-assembled monolayers of
      cyclic and acyclic polyethers.
AB  - Our recent work with cyclic and acyclic polyether self-assembled monolayers
      (SAMs) on gold is presented. A series of dithia-crown-tetrathiafulvalene
      derivatives with one or two disulfide groups has been prepared, and their SAMs on
      gold have been characterized by electrochemistry and by reflection-absorption
      infrared spectroscopy. These SAMs are extremely stable on repeated
      electrochemical potential scans and can selectively recognize alkali metal ions.
      Acyclic polyether derivatives can also self-assemble on gold to yield selective
      metal ion recognition domains. Impedance spectroscopy data for these SAMs fit the
      Langmuir isotherm and allow the determination of ion association constants. Some
      of the SAMs prepared with new acyclic polyether derivatives are able to detect
      potassium cations selectively when templated in their presence. These structures
      are believed to be a consequence of ion "imprinting" during the process of SAM
      formation.

PMID- 11959956
TI  - Selective immobilization of proteins to self-assembled monolayers presenting
      active site-directed capture ligands.
AB  - This paper describes a method for the selective and covalent immobilization of
      proteins to surfaces with control over the density and orientation of the
      protein. The strategy is based on binding of the serine esterase cutinase to a
      self-assembled monolayer presenting a phosphonate ligand and the subsequent
      displacement reaction that covalently binds the ligand to the enzyme active site.
      Surface plasmon resonance (SPR) spectroscopy showed that cutinase binds
      irreversibly to a monolayer presenting the capture ligand at a density of 1%
      mixed among tri(ethylene glycol) groups. The covalent immobilization is specific
      for cutinase, and the glycol-terminated monolayer effectively prevents unwanted
      nonspecific adsorption of proteins. To demonstrate that the method could be used
      to immobilize proteins of interest, a cutinase-calmodulin fusion protein was
      constructed and immobilized to the monolayer. SPR showed that calcineurin
      selectively associated with the immobilized calmodulin. This capture ligand
      immobilization method combines the advantages that the immobilization reaction is
      highly selective for the intended protein, the tether is covalent and, hence,
      stable, and the method avoids the need for synthetic modification and rigorous
      purification of proteins before immobilization. These characteristics make the
      method well suited to a range of applications and, in particular, for
      constructing protein microarrays.

PMID- 11959957
TI  - Intramolecular DNA coiling mediated by metallo-supramolecular cylinders:
      differential binding of P and M helical enantiomers.
AB  - We have designed a synthetic tetracationic metallo-supramolecular cylinder that
      targets the major groove of DNA with a binding constant in excess of 10(7) M(-1)
      and induces DNA bending and intramolecular coiling. The two enantiomers of the
      helical molecule bind differently to DNA and have different structural effects.
      We report the characterization of the interactions by a range of biophysical
      techniques. The M helical cylinder binds to the major groove and induces dramatic
      intramolecular coiling. The DNA bending is less dramatic for the P enantiomer.

PMID- 11959958
TI  - Supramolecular self-assembled fullerene nanostructures.
AB  - Four ionic fullerene derivatives, which are relatively soluble in polar solvents,
      are shown to organize into morphologically different nanoscale structures.
      Spheres, nanorods, and nanotubules form in water depending on the side chain
      appendage of the fullerene spheroid. Images at different nanoscale structures
      were obtained via transmission electron microscopy. Also, computer simulations
      were used for investigating the relative spatial arrangements. The efficient
      method to fabricate almost perfect and uniformly shaped nanotubular crystals,
      which order spontaneously by self-assembly, opens the way to the possibility of
      exploiting the fullerene properties at the nanometer scale.

PMID- 11959959
TI  - Plastic- and liquid-crystalline architectures from dendritic receptor molecules.
AB  - Host molecules with U-shaped receptor cavities have been derivatized at their
      convex side with two n-hydrocarbon tails (1), two first-generation (2), and two
      second-generation (3) monodendritic hydrocarbon tails. Although hosts 1 and 2
      display plastic-crystalline behavior, evidence suggests that host 3 forms a cubic
      liquid-crystalline phase. In this phase, molecules of 3 are arranged in spherical
      supramacromolecular assemblies, in which the receptor cavities are situated in
      the core and the hydrocarbon tails at the periphery. The 1:1 host-guest complex
      of 3 with methyl 3,5dihydroxybenzoate forms a similar liquid-crystalline phase,
      with the guest included in the core of the assemblies.

PMID- 11959960
TI  - Modulation of protein-protein interactions by synthetic receptors: design of
      molecules that disrupt serine protease-proteinaceous inhibitor interaction.
AB  - In the present article we describe the design and evaluation of a synthetic
      receptor that binds to the exterior surface of chymotrypsin and disrupts its
      interaction with proteinaceous inhibitors, such as soybean trypsin inhibitor,
      basic pancreatic trypsin inhibitor, ovomucoid turkey inhibitor, and Bowman-Birk
      inhibitor. Using enzyme kinetics, nondenaturing gel electrophoresis, and gel
      filtration chromatography we show that the receptor is particularly effective at
      blocking the chymotrypsin-soybean trypsin inhibitor complex and that the
      mechanism involves formation of an initial ternary complex followed by a time
      dependent displacement of the proteinaceous inhibitor.

PMID- 11959961
TI  - De novo design of biomimetic antimicrobial polymers.
AB  - The design of polymers and oligomers that mimic the complex structures and
      remarkable biological properties of proteins is an important endeavor with both
      fundamental and practical implications. Recently, a number of nonnatural peptides
      with designed sequences have been elaborated to provide biologically active
      structures; in particular, facially amphiphilic peptides built from beta-amino
      acids have been shown to mimic both the structures as well as the biological
      function of natural antimicrobial peptides such as magainins and cecropins.
      However, these natural peptides as well as their beta-peptide analogues are
      expensive to prepare and difficult to produce on a large scale, limiting their
      potential use to certain pharmaceutical applications. We therefore have designed
      a series of facially amphiphilic arylamide polymers that capture the physical and
      biological properties of this class of antimicrobial peptides, but are easy to
      prepare from inexpensive monomers. The design process was aided by molecular
      calculations with density functional theory-computed torsional potentials. This
      new class of amphiphilic polymers may be applied in situations where inexpensive
      antimicrobial agents are required.

PMID- 11959962
TI  - Fibronectin extension and unfolding within cell matrix fibrils controlled by
      cytoskeletal tension.
AB  - Evidence is emerging that mechanical stretching can alter the functional states
      of proteins. Fibronectin (Fn) is a large, extracellular matrix protein that is
      assembled by cells into elastic fibrils and subjected to contractile forces.
      Assembly into fibrils coincides with expression of biological recognition sites
      that are buried in Fn's soluble state. To investigate how supramolecular assembly
      of Fn into fibrillar matrix enables cells to mechanically regulate its structure,
      we used fluorescence resonance energy transfer (FRET) as an indicator of Fn
      conformation in the fibrillar matrix of NIH 3T3 fibroblasts. Fn was randomly
      labeled on amine residues with donor fluorophores and site-specifically labeled
      on cysteine residues in modules FnIII(7) and FnIII(15) with acceptor
      fluorophores. Intramolecular FRET was correlated with known structural changes of
      Fn in denaturing solution, then applied in cell culture as an indicator of Fn
      conformation within the matrix fibrils of NIH 3T3 fibroblasts. Based on the level
      of FRET, Fn in many fibrils was stretched by cells so that its dimer arms were
      extended and at least one FnIII module unfolded. When cytoskeletal tension was
      disrupted using cytochalasin D, FRET increased, indicating refolding of Fn within
      fibrils. These results suggest that cell-generated force is required to maintain
      Fn in partially unfolded conformations. The results support a model of Fn fibril
      elasticity based on unraveling and refolding of FnIII modules. We also observed
      variation of FRET between and along single fibrils, indicating variation in the
      degree of unfolding of Fn in fibrils. Molecular mechanisms by which mechanical
      force can alter the structure of Fn, converting tensile forces into biochemical
      cues, are discussed.

PMID- 11959963
TI  - Noncovalent self-assembly of a heterotetrameric diiron protein.
AB  - Diiron and dimanganese proteins catalyze a wide range of hydrolytic and oxygen
      dependent reactions. To probe the mechanisms by which individual members of this
      class of proteins are able to catalyze such a wide range of reactions, we have
      prepared a model four-helix bundle with a diiron site located near the center of
      the bundle. The four-helix bundle is constructed by the noncovalent self-assembly
      of three different chains (A(a), A(b), and B) that self-assemble into the desired
      heterotetramer when mixed in a 1:1:2 molar ratio. On addition of ferrous ions and
      oxygen, the protein forms a complex with a UV-visible spectrum closely resembling
      that of peroxo-bridged diferric species in natural proteins and model compounds.
      By combining a small collection of n variants of these peptides, it should now be
      possible to prepare an n(3) member library, which will allow systematic
      exploration of the features giving rise to the catalytic properties of this class
      of proteins.

PMID- 11959964
TI  - Investigation of the role of ansocalcin in the biomineralization in goose
      eggshell matrix.
AB  - The role of proteins in biomineralization and the mechanism of eggshell formation
      are not well understood. We have isolated and purified the major protein,
      ansocalcin from goose eggshell matrix. The amino acid sequence study indicates
      that ansocalcin is homologous to the chicken eggshell protein, ovocleidin 17, and
      C-type lectins. Ansocalcin nucleates polycrystalline aggregates of calcite
      crystals in in vitro mineralization experiments. The polycrystalline aggregates
      obtained at higher concentration of ansocalcin appears to be similar to the
      crystals observed at the mamillary layer of the eggshell.

PMID- 11959965
TI  - Positioning protein molecules on surfaces: a nanoengineering approach to
      supramolecular chemistry.
AB  - We discuss a nanoengineering approach for supramolecular chemistry and self
      assembly. The collective properties and biofunctionalities of molecular ensembles
      depend not only on individual molecular building blocks but also on organization
      at the molecular or nanoscopic level. Complementary to "bottom-up" approaches,
      which construct supramolecular ensembles by the design and synthesis of
      functionalized small molecular units or large molecular motifs, nanofabrication
      explores whether individual units, such as small molecular ligands, or large
      molecules, such as proteins, can be positioned with nanometer precision. The
      separation and local environment can be engineered to control subsequent
      intermolecular interactions. Feature sizes as small as 2 x 4 nm(2) (32
      alkanethiol molecules) are produced. Proteins may be aligned along a 10-nm-wide
      line or within two-dimensional islands of desired geometry. These high-resolution
      engineering and imaging studies provide new and molecular-level insight into
      supramolecular chemistry and self-assembly processes in bioscience that are
      otherwise unobtainable, e.g., the influence of size, separation, orientation, and
      local environment of reaction sites. This nanofabrication methodology also offers
      a new strategy in construction of two- and three-dimensional supramolecular
      structures for cell, virus, and bacterial adhesion, as well as biomaterial and
      biodevice engineering.

PMID- 11959966
TI  - Shape-selective transport through rectangle-based molecular materials: thin-film
      scanning electrochemical microscopy studies.
AB  - Microporous thin films (approximately equal to 50 to 400 nm) composed of
      discrete, cavity-containing molecular rectangles have been prepared. The films,
      which contain both amorphous and microcrystalline domains, display shape
      selective transport behavior. They are permeable to small molecules and to
      molecules that are short or narrow in at least one dimension--for example,
      elongated planar molecules--but are impermeable to molecules lacking a narrow
      dimension. However, the shape selectivity is based on transport through
      intramolecular rather than intermolecular cavities. By using redox-active probe
      molecules, rates of transport through the rectangle-based material have been
      extracted from electrochemical measurements. Spatially resolved measurements
      obtained via scanning electrochemical microscopy have permitted transport through
      individual microcrystals to be evaluated semiquantitatively. The measurements
      reveal that transport is roughly two orders of magnitude slower than observed
      with thin microcrystalline films of molecular squares featuring similar-sized
      cavities. The differences likely reflect the fact that cavities within the square
      based materials, but not the rectangle-based material, align to form simple one
      dimensional channels.

PMID- 11959973
TI  - Early statistical detection of anthrax outbreaks by tracking over-the-counter
      medication sales.
AB  - The recent series of anthrax attacks has reinforced the importance of
      biosurveillance systems for the timely detection of epidemics. This paper
      describes a statistical framework for monitoring grocery data to detect a large
      scale but localized bioterrorism attack. Our system illustrates the potential of
      data sources that may be more timely than traditional medical and public health
      data. The system includes several layers, each customized to grocery data and
      tuned to finding footprints of an epidemic. We also propose an evaluation
      methodology that is suitable in the absence of data on large-scale bioterrorist
      attacks and disease outbreaks.

PMID- 11959967
TI  - Iron uptake in ferritin is blocked by binding of [Cr(TREN)(H(2)O)(OH)](2+), a
      slow dissociating model for [Fe(H(2)O)(6)](2+).
AB  - Ferritin concentrates iron as a hydrous ferric oxide in a protein cavity (8 nm in
      diameter) by using eight pores along the threefold symmetry axes of the
      octahedral supramolecular structure. The role of ligand exchange in the entry of
      Fe(II) hexahydrate into ferritin protein has been studied with
      [Cr(TREN)(H(2)O)(OH)](2+) [TREN = N(CH(2)CH(2)NH(2))(3)], a model for
      Fe(H(2)O)(6)2+ with only two exchangeable ligands. The results show that five
      different ferritin proteins, varying in pore structure, oxidation sites, and
      nucleation sites, bind Cr(TREN) at functional protein sites, based on inhibition
      of iron mineralization and oxidation. Properties of Cr(TREN)-ferritin adducts
      include an increased isoelectric point, a shift in the Cr(TREN) UV/vis spectrum
      consistent with exchange of water for protein carboxylate or thiolate ligands,
      binding affinities of 50-250 microM, and a slow rate of dissociation (k = 4 x 10(
      6) sec(-1)). The relationship of Cr(TREN) inhibition of iron oxidation and
      mineralization by Cr(TREN) to the known structures of the various ferritins
      tested suggests that Cr(TREN) plugs the ferritin pores, obstructing Fe(II) entry
      in folded and unfolded pores. Because only two exchangeable waters are sufficient
      for pore binding of Cr(TREN), the physiological Fe(II) donor must bind to the
      pore with few exchangeable ligands. These results show the advantage of using
      stable model complexes to explore properties of transient Fe-protein complexes
      during Fe mineralization in ferritin.

PMID- 11959974
TI  - Human antibodies against spores of the genus Bacillus: a model study for
      detection of and protection against anthrax and the bioterrorist threat.
AB  - A naive, human single-chain Fv (scFv) phage-display library was used in bio
      panning against live, native spores of Bacillus subtilis IFO 3336 suspended in
      solution. A direct in vitro panning and enzyme-linked immunosorbent assay-based
      selection afforded a panel of nine scFv-phage clones of which two, 5B and 7E,
      were chosen for further study. These two clones differed in their relative
      specificity and affinity for spores of B. subtilis IFO 3336 vs. a panel of spores
      from 11 other Bacillus species/strains. A variety of enzyme-linked immunosorbent
      assay protocols indicated these scFv-phage clones recognized different spore
      epitopes. Notably, some spore epitopes markedly changed between the free and
      microtiter-plate immobilized state as revealed by antibody-phage binding. An
      additional library selection procedure also was examined by constructing a Fab
      chain-shuffled sublibrary from the nine positive clones and by using a
      subtractive panning strategy to remove crossreactivity with B. licheniformis
      5A24. The Fab-phage clone 52 was improved compared with 5B and was comparable to
      7E in binding B. subtilis IFO 3336 vs. B. licheniformis 5A24, yet showed a
      distinctive crossreactivity pattern with other spores. We also developed a method
      to directly detect individual spores by using fluorescently labeled antibody
      phage. Finally, a variety of "powders" that might be used in deploying spores of
      B. anthracis were examined for antibody-phage binding. The strategies described
      provide a foundation to discover human antibodies specific for native spores of
      B. anthracis that can be developed as diagnostic and therapeutic reagents.

PMID- 11959975
TI  - Mechanism of inactivation on prion conversion of the Saccharomyces cerevisiae
      Ure2 protein.
AB  - The [URE3] infectious protein (prion) of Saccharomyces cerevisiae is a self
      propagating amyloid form of Ure2p. The C-terminal domain of Ure2p controls
      nitrogen catabolism by complexing with the transcription factor, Gln3p, whereas
      the asparagine-rich N-terminal "prion" domain is responsible for amyloid filament
      formation (prion conversion). On filament formation, Ure2p is inactivated,
      reflecting either a structural change in the C-terminal domain or steric blocking
      of its interaction with Gln3p. We fused the prion domain with four proteins whose
      activities should not be sterically impeded by aggregation because their
      substrates are very small: barnase, carbonic anhydrase, glutathione S
      transferase, and green fluorescent protein. All formed amyloid filaments in
      vitro, whose diameters increased with the mass of the appended enzyme. The
      helical repeat lengths were consistent within a single filament but varied with
      the construct and between filaments from a single construct. CD data suggest
      that, in the soluble fusion proteins, the prion domain has no regular secondary
      structure, whereas earlier data showed that in filaments, it is virtually all
      beta-sheet. In filaments, the activity of the appended proteins was at most
      mildly reduced, when substrate diffusion effects were taken into account,
      indicating that they retained their native structures. These observations suggest
      that the amyloid content of these filaments is confined to their prion domain
      containing backbones and imply that Ure2p is inactivated in [URE3] cells by a
      steric blocking mechanism.

PMID- 11959976
TI  - Comprehensive human genome amplification using multiple displacement
      amplification.
AB  - Fundamental to most genetic analysis is availability of genomic DNA of adequate
      quality and quantity. Because DNA yield from human samples is frequently
      limiting, much effort has been invested in developing methods for whole genome
      amplification (WGA) by random or degenerate oligonucleotide-primed PCR. However,
      existing WGA methods like degenerate oligonucleotide-primed PCR suffer from
      incomplete coverage and inadequate average DNA size. We describe a method, termed
      multiple displacement amplification (MDA), which provides a highly uniform
      representation across the genome. Amplification bias among eight chromosomal loci
      was less than 3-fold in contrast to 4-6 orders of magnitude for PCR-based WGA
      methods. Average product length was >10 kb. MDA is an isothermal, strand
      displacing amplification yielding about 20-30 microg product from as few as 1-10
      copies of human genomic DNA. Amplification can be carried out directly from
      biological samples including crude whole blood and tissue culture cells. MDA
      amplified human DNA is useful for several common methods of genetic analysis,
      including genotyping of single nucleotide polymorphisms, chromosome painting,
      Southern blotting and restriction fragment length polymorphism analysis,
      subcloning, and DNA sequencing. MDA-based WGA is a simple and reliable method
      that could have significant implications for genetic studies, forensics,
      diagnostics, and long-term sample storage.

PMID- 11959978
TI  - Stop codons affect 5' splice site selection by surveillance of splicing.
AB  - Pre-mRNA splicing involves recognition of a consensus sequence at the 5' splice
      site (SS). However, only some of the many potential sites that conform to the
      consensus are true ones, whereas the majority remain silent and are not normally
      used for splicing. We noticed that in most cases the utilization of such a latent
      intronic 5' SS for splicing would introduce an in-frame stop codon into the
      resultant mRNA. This finding suggested a link between SS selection and
      maintenance of an ORF within the mRNA. Here we tested this idea by analyzing the
      splicing of pre-mRNAs in which in-frame stop codons upstream of a latent 5' SS
      were mutated. We found that splicing with the latent site is indeed activated by
      such mutations. Our findings predict the existence of a checking mechanism, as a
      component of the nuclear pre-mRNA splicing machine, to ensure the maintenance of
      an ORF. This notion is highly important for accurate gene expression, as
      perturbations that would lead to splicing at these latent sites are expected to
      introduce in-frame stop codons into the majority of mRNAs.

PMID- 11959977
TI  - Structural basis for Hif-1 alpha /CBP recognition in the cellular hypoxic
      response.
AB  - The cellular response to low tissue oxygen concentrations is mediated by the
      hypoxia-inducible transcription factor HIF-1. Under hypoxic conditions, HIF-1
      activates transcription of critical adaptive genes by recruitment of the general
      coactivators CBP/p300 through interactions with its alpha-subunit (Hif-1 alpha).
      Disruption of the Hif-1 alpha/p300 interaction has been linked to attenuation of
      tumor growth. To delineate the structural basis for this interaction, we have
      determined the solution structure of the complex between the carboxy-terminal
      activation domain (CAD) of Hif-1 alpha and the zinc-binding TAZ1 (CH1) motif of
      cyclic-AMP response element binding protein (CREB) binding protein (CBP). Despite
      the overall similarity of the TAZ1 structure to that of the TAZ2 (part of the
      CH3) domain of CBP, differences occur in the packing of helices that can account
      for differences in specificity. The unbound CAD is intrinsically disordered and
      remains relatively extended upon binding, wrapping almost entirely around the
      TAZ1 domain in a groove through much of its surface. Three short helices are
      formed upon binding, stabilized by intermolecular interactions. The Asn-803 side
      chain, which functions as a hypoxic switch, is located on the second of these
      helices and is buried in the molecular interface. The third helix of the Hif-1
      alpha CAD docks in a deep hydrophobic groove in TAZ1, providing extensive
      intermolecular hydrophobic interactions that contribute to the stability of the
      complex. The structure of this complex provides new insights into the mechanism
      through which Hif-1 alpha recruits CBP/p300 in response to hypoxia.

PMID- 11959979
TI  - Protein deamidation.
AB  - A completely automatic computerized technique for the quantitative estimation of
      the deamidation rates of any protein for which the three-dimensional structure is
      known has been developed. Calculations of the specific deamidation rates of
      170,014 asparaginyl residues in 13,335 proteins have been carried out. The
      calculated values have good quantitative reliability when compared with
      experimental measurements. These rates demonstrate that deamidation may be a
      biologically relevant phenomenon in a remarkably large percentage of proteins.

PMID- 11959980
TI  - In vitro reconstitution and activity of a C/D box methylation guide
      ribonucleoprotein complex.
AB  - The genomes of hyperthermophilic Archaea encode dozens of methylation guide, C/D
      box small RNAs that guide 2'-O-methylation of ribose to specific sites in rRNA
      and various tRNAs. The genes encoding the Sulfolobus homologues of eukaryotic
      proteins that are known to be present in C/D box small nucleolar
      ribonucleoprotein (snoRNP) complexes were cloned, and the proteins (aFIB, aNOP56,
      and aL7a) were expressed and purified. The purified proteins along with an in
      vitro transcript of the Sulfolobus sR1 small RNA were reconstituted in vitro,
      into an RNP complex. The order of assembly of the three proteins onto the RNA was
      aL7a, aNOP56, and aFIB. The complex was active in targeting S-adenosyl methionine
      (SAM)-dependent, site-specific 2'-O-methylation of ribose to a short fragment of
      ribosomal RNA (rRNA) that was complementary to the D box guide region of the sR1
      small RNA. The presence of aFIB was essential for methylation; mutant proteins
      having amino acid replacements in the SAM-binding motif of aFIB were able to
      assemble into an RNP complex, but the resulting complexes were defective in
      methylation activity. These experiments define the minimal number of components
      and the conditions required to achieve in vitro RNA guide-directed 2'-O
      methylation of ribose in a target RNA.

PMID- 11959981
TI  - Polypurine (A)-rich sequences promote cross-kingdom conservation of internal
      ribosome entry.
AB  - The internal ribosome entry sites (IRES), IRES(CP,148)(CR) and IRES(MP,75)(CR),
      precede the coat protein (CP) and movement protein (MP) genes of crucifer
      infecting tobamovirus (crTMV), respectively. In the present work, we analyzed the
      activity of these elements in transgenic plants and other organisms. Comparison
      of the relative activities of the crTMV IRES elements and the IRES from an animal
      virus--encephalomyocarditis virus--in plant, yeast, and HeLa cells identified the
      148-nt IRES(CP,148)(CR) as the strongest element that also displayed IRES
      activity across all kingdoms. Deletion analysis suggested that the polypurine (A)
      rich sequences (PARSs) contained in IRES(CP,148)(CR) are responsible for these
      features. On the basis of those findings, we designed artificial PARS-containing
      elements and showed that they, too, promote internal translation from dicistronic
      transcripts in vitro, in tobacco protoplasts and in HeLa cells. The maximum IRES
      activity was obtained from multiple copies of either (A)(4)G(A)(2)(G)(2) or
      G(A)(2-5) as contained in IRES(CP,148)(CR). Remarkably, even homopolymeric
      poly(A) was moderately active, whereas a poly(G) homopolymer was not active.
      Furthermore, a database search for existing PARS sequences in 5'-untranslated
      regions (5'UTR) of genes in tobacco genome allowed the easy identification of a
      number of IRES candidates, in particular in the 5'UTR of the gene encoding
      Nicotiana tabacum heat-shock factor 1 (NtHSF1). Consistent with our prediction,
      the 5'UTR of NtHSF1 turned out to be an IRES element active in vitro, in plant
      protoplasts and HeLa cells. We predict that PARS elements, when found in other
      mRNAs, will show a similar activity.

PMID- 11959982
TI  - Posttranslational modification of the umuD-encoded subunit of Escherichia coli
      DNA polymerase V regulates its interactions with the beta processivity clamp.
AB  - The Escherichia coli umuDC (pol V) gene products participate in both a DNA damage
      checkpoint control and translesion DNA synthesis. Interactions of the two umuD
      gene products, the 139-aa UmuD and the 115-aa UmuD' proteins, with components of
      the replicative DNA polymerase (pol III), are important for determining which
      biological role the umuDC gene products will play. Here we report our biochemical
      characterizations of the interactions of UmuD and UmuD' with the pol III beta
      processivity clamp. These analyses demonstrate that UmuD possesses a higher
      affinity for beta than does UmuD' because of the N-terminal arm of UmuD (residues
      1-39), much of which is missing in UmuD'. Furthermore, we have identified
      specific amino acid residues of UmuD that crosslink to beta with p
      azidoiodoacetanilide, defining the domain of UmuD important for the interaction.
      We have recently proposed a model for the solution structure of UmuD(2) in which
      the N-terminal arm of each protomer makes extensive contacts with the C-terminal
      globular domain of its intradimer partner, masking part of each surface. Taken
      together, our findings suggest that UmuD(2) has a higher affinity for the beta
      clamp than does UmuD'(2) because of the structures of its N-terminal arms. Viewed
      in this way, posttranslational modification of UmuD, which entails the removal of
      its N-terminal 24 residues to yield UmuD', acts in part to attenuate the affinity
      of the umuD gene product for the beta-clamp. Implications of these structure
      function analyses for the checkpoint and translesion DNA synthesis functions of
      the umuDC gene products are discussed.

PMID- 11959984
TI  - Expanding the biosynthetic repertoire of plant type III polyketide synthases by
      altering starter molecule specificity.
AB  - Type III polyketide synthases (PKS) generate an array of natural products by
      condensing multiple acetyl units derived from malonyl-CoA to thioester-linked
      starter molecules covalently bound in the PKS active site. One strategy adopted
      by Nature for increasing the functional diversity of these biosynthetic enzymes
      involves modifying polyketide assembly by altering the preference for starter
      molecules. Chalcone synthase (CHS) is a ubiquitous plant PKS and the first type
      III PKS described functionally and structurally. Guided by the three-dimensional
      structure of CHS, Phe-215 and Phe-265, which are situated at the active site
      entrance, were targeted for site-directed mutagenesis to diversify CHS activity.
      The resulting mutants were screened against a panel of aliphatic and aromatic CoA
      linked starter molecules to evaluate the degree of starter molecule specificity
      in CHS. Although wild-type CHS accepts a number of natural CoA thioesters, it
      does not use N-methylanthraniloyl-CoA as a substrate. Substitution of Phe-215 by
      serine yields a CHS mutant that preferentially accepts this CoA-thioester
      substrate to generate a novel alkaloid, namely N-methylanthraniloyltriacetic acid
      lactone. These results demonstrate that a point mutation in CHS dramatically
      shifts the molecular selectivity of this enzyme. This structure-based approach to
      metabolic redesign represents an initial step toward tailoring the biosynthetic
      activity of plant type III PKS.

PMID- 11959983
TI  - Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin
      resistance associated with defects in Akt activation in 3T3-L1 adipocytes.
AB  - Increased flux of glucose through the hexosamine biosynthetic pathway (HSP) is
      believed to mediate hyperglycemia-induced insulin resistance in diabetes. The end
      product of the HSP, UDP beta-N-acetylglucosamine (GlcNAc), is a donor sugar
      nucleotide for complex glycosylation in the secretory pathway and for O-linked
      GlcNAc (O-GlcNAc) addition to nucleocytoplasmic proteins. Cycling of the O-GlcNAc
      posttranslational modification was blocked by pharmacological inhibition of O
      GlcNAcase, the enzyme that catalyzes O-GlcNAc removal from proteins, with O-(2
      acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc). PUGNAc
      treatment increased levels of O-GlcNAc and caused insulin resistance in 3T3-L1
      adipocytes. Insulin resistance induced through the HSP by glucosamine and chronic
      insulin treatment correlated with increased O-GlcNAc levels on nucleocytoplasmic
      proteins. Whereas insulin receptor autophosphorylation and insulin receptor
      substrate 2 tyrosine phosphorylation were not affected by PUGNAc inhibition of O
      GlcNAcase, downstream phosphorylation of Akt at Thr-308 and glycogen synthase
      kinase 3 beta at Ser-9 was inhibited. PUGNAc-induced insulin resistance was
      associated with increased O-GlcNAc modification of several proteins including
      insulin receptor substrate 1 and beta-catenin, two important effectors of insulin
      signaling. These results suggest that elevation of O-GlcNAc levels attenuate
      insulin signaling and contribute to the mechanism by which increased flux through
      the HSP leads to insulin resistance in adipocytes.

PMID- 11959985
TI  - Holocarboxylase synthetase is an obligate participant in biotin-mediated
      regulation of its own expression and of biotin-dependent carboxylases mRNA levels
      in human cells.
AB  - Holocarboxylase synthetase (HCS) catalyzes the covalent attachment of biotin to
      five biotin-dependent carboxylases in human cells. Multiple carboxylase
      deficiency (MCD) is a life-threatening disease characterized by the lack of
      carboxylase activities because of deficiency of HCS activity. Here, we report the
      obligatory participation of HCS in the biotin-dependent stimulation of the level
      of HCS mRNA and those of acetyl-CoA carboxylase and the alpha subunit of
      propionyl-CoA carboxylase in human cells. Fibroblasts from patients with MCD are
      unable to increase HCS mRNA in response to biotin unless the vitamin
      concentration is raised 100-fold, in keeping with mutations that cause a reduced
      affinity for biotin by the mutant enzyme. The outcome is deficient synthesis of
      biotinyl-5'-AMP, the active form of the vitamin in the biotinylation reaction.
      HCS and carboxylase mRNA levels in normal and MCD fibroblasts and HepG2 cells can
      be restored by the addition of the cGMP analogue, 8-Br-cGMP, and can be abolished
      by the addition of inhibitors of the soluble form of guanylate cyclase. We
      propose a regulatory role for biotin in the control of HCS and carboxylase mRNA
      levels through a signaling cascade that requires HCS, guanylate cyclase, and cGMP
      dependent protein kinase.

PMID- 11959986
TI  - The frameshift signal of HIV-1 involves a potential intramolecular triplex RNA
      structure.
AB  - The cis-acting mRNA elements that promote programmed -1 ribosomal frameshifting
      present a natural target for the rational design of antiretroviral
      chemotherapies. It has been commonly accepted that the HIV-1 frameshifting signal
      is special, because its downstream enhancer element consists of a simple mRNA
      stem loop rather than a more complex secondary structure such as a pseudoknot.
      Here we present three lines of evidence, bioinformatic, structural, and genetic,
      showing that the biologically relevant HIV-1 frameshift signal contains a complex
      RNA structure that likely includes an extended RNA triple-helix region. We
      suggest that the potential intramolecular triplex structure is essential for
      viral propagation and viability, and that small molecules targeted to this RNA
      structure may possess antiretroviral activities.

PMID- 11959988
TI  - Unspecific hydrophobic stabilization of folding transition states.
AB  - Here we present a method for determining the inference of non-native
      conformations in the folding of a small domain, alpha-spectrin Src homology 3
      domain. This method relies on the preservation of all native interactions after
      Tyr/Phe exchanges in solvent-exposed, contact-free positions. Minor changes in
      solvent exposure and free energy of the denatured ensemble are in agreement with
      the reverse hydrophobic effect, as the Tyr/Phe mutations slightly change the
      polypeptide hydrophilic/hydrophobic balance. Interestingly, more important Gibbs
      energy variations are observed in the transition state ensemble (TSE).
      Considering the small changes induced by the H/OH replacements, the observed
      energy variations in the TSE are rather notable, but of a magnitude that would
      remain undetected under regular mutations that alter the folded structure free
      energy. Hydrophobic residues outside of the folding nucleus contribute to the
      stability of the TSE in an unspecific nonlinear manner, producing a significant
      acceleration of both unfolding and refolding rates, with little effect on
      stability. These results suggest that sectors of the protein transiently reside
      in non-native areas of the landscape during folding, with implications in the
      reading of phi values from protein engineering experiments. Contrary to previous
      proposals, the principle that emerges is that non-native contacts, or
      conformations, could be beneficial in evolution and design of some fast folding
      proteins.

PMID- 11959987
TI  - Stimulation of retinoic acid production and growth by ubiquitously expressed
      alcohol dehydrogenase Adh3.
AB  - Influence of vitamin A (retinol) on growth depends on its sequential oxidation to
      retinal and then to retinoic acid (RA), producing a ligand for RA receptors
      essential in development of specific tissues. Genetic studies have revealed that
      aldehyde dehydrogenases function as tissue-specific catalysts for oxidation of
      retinal to RA. However, enzymes catalyzing the first step of RA synthesis,
      oxidation of retinol to retinal, remain unclear because none of the present
      candidate enzymes have expression patterns that fully overlap with those of
      aldehyde dehydrogenases during development. Here, we provide genetic evidence
      that alcohol dehydrogenase (ADH) performs this function by demonstrating a role
      for Adh3, a ubiquitously expressed form. Adh3 null mutant mice exhibit reduced RA
      generation in vivo, growth deficiency that can be rescued by retinol
      supplementation, and completely penetrant postnatal lethality during vitamin A
      deficiency. ADH3 was also shown to have in vitro retinol oxidation activity.
      Unlike the second step, the first step of RA synthesis is not tissue-restricted
      because it is catalyzed by ADH3, a ubiquitous enzyme having an ancient origin.

PMID- 11959989
TI  - Comparison of the dynamics of substrate access channels in three cytochrome P450s
      reveals different opening mechanisms and a novel functional role for a buried
      arginine.
AB  - Understanding the mechanism and specificity of substrate binding in the
      cytochrome P450 (P450) superfamily is an important step toward explaining its key
      role in drug metabolism, toxicity, xenobiotic degradation, and several
      biosynthetic pathways. Here we investigate the ligand exit pathways and
      mechanisms of P450cam (CYP101), P450BM-3 (CYP102), and P450eryF (CYP107A1) by
      using random expulsion molecular dynamics and classical molecular dynamics
      simulations. Although several different pathways are found for each protein, one
      pathway is common to all three. The mechanism of ligand exit along this pathway
      is, however, quite different in the three different proteins. For P450cam, small
      backbone conformational changes, in combination with aromatic side chain
      rotation, allow for the passage of the rather rigid, compact, and hydrophobic
      substrate, camphor. In P450BM-3, larger transient backbone changes are observed
      on ligand exit. R47, situated at the entrance to the channel, appears important
      in guiding negatively charged fatty acid substrates in and out of the active
      site. In P450eryF, an isolated buried arginine, R185, stabilized by four hydrogen
      bonds to backbone carbonyl oxygen atoms, is located in the exit channel and is
      identified as having a particularly unusual functionality, dynamically gating
      channel opening. The results for these three P450s suggest that the channel
      opening mechanisms are adjusted to the physico-chemical properties of the
      substrate and can kinetically modulate protein-substrate specificity.

PMID- 11959991
TI  - Knotting probability of DNA molecules confined in restricted volumes: DNA
      knotting in phage capsids.
AB  - When linear double-stranded DNA is packed inside bacteriophage capsids, it
      becomes highly compacted. However, the phage is believed to be fully effective
      only if the DNA is not entangled. Nevertheless, when DNA is extracted from a
      tailless mutant of the P4 phage, DNA is found to be cyclic and knotted
      (probability of 0.95). The knot spectrum is very complex, and most of the knots
      have a large number of crossings. We quantified the frequency and crossing
      numbers of these knots and concluded that, for the P4 tailless mutant, at least
      half the knotted molecules are formed while the DNA is still inside the viral
      capsid rather than during extraction. To analyze the origin of the knots formed
      inside the capsid, we compared our experimental results to Monte Carlo
      simulations of random knotting of equilateral polygons in confined volumes. These
      simulations showed that confinement of closed chains to tightly restricted
      volumes results in high knotting probabilities and the formation of knots with
      large crossing numbers. We conclude that the formation of the knots inside the
      viral capsid is driven mainly by the effects of confinement.

PMID- 11959990
TI  - Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha.
AB  - Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes
      by hypoxia-inducible factor-1 (HIF-1) in complex with the CBP and p300
      transcriptional coactivators. We report the solution structure of the
      cysteine/histidine-rich 1 (CH1) domain of p300 bound to the C-terminal
      transactivation domain of HIF-1 alpha. CH1 has a triangular geometry composed of
      four alpha-helices with three intervening Zn(2+)-coordinating centers. CH1 serves
      as a scaffold for folding of the HIF-1 alpha C-terminal transactivation domain,
      which forms a vise-like clamp on the CH1 domain that is stabilized by extensive
      hydrophobic and polar interactions. The structure reveals the mechanism of
      specific recognition of p300 by HIF-1 alpha, and shows how HIF-1 alpha
      transactivation is regulated by asparagine hydroxylation.

PMID- 11959992
TI  - Is the first hydration shell of lysozyme of higher density than bulk water?
AB  - Characterization of the physical properties of protein surface hydration water is
      critical for understanding protein structure and folding. Here, using molecular
      dynamics simulation, we provide an explanation of recent x-ray and neutron
      solution scattering data that indicate that the density of water on the surface
      of lysozyme is significantly higher than that of bulk water. The simulation
      derived scattering profiles are in excellent agreement with the experiment. In
      the simulation, the 3-A-thick first hydration layer is 15% denser than bulk
      water. About two-thirds of this increase is the result of a geometric
      contribution that would also be present if the water was unperturbed from the
      bulk. The remaining third arises from modification of the water structure and
      dynamics, involving approximately equal contributions from shortening of the
      average water-water O-O distance and an increase in the coordination number.
      Variation in the first hydration shell density is shown to be determined by
      topographical and electrostatic properties of the protein surface. On average,
      denser water is found in depressions on the surface in which the water dipoles
      tend to be aligned parallel to each other by the electrostatic field generated by
      the protein atoms.

PMID- 11959994
TI  - A minimal system allowing tubulation with molecular motors pulling on giant
      liposomes.
AB  - The elucidation of physical and molecular mechanisms by which a membrane tube is
      generated from a membrane reservoir is central to the understanding of the
      structure and dynamics of intracellular organelles and of transport intermediates
      in eukaryotic cells. Compelling evidence exists that molecular motors of the
      dynein and kinesin families are involved in the tubulation of organelles. Here,
      we show that lipid giant unilamellar vesicles (GUVs), to which kinesin molecules
      have been attached by means of small polystyrene beads, give rise to membrane
      tubes and to complex tubular networks when incubated in vitro with microtubules
      and ATP. Similar tubes and networks are obtained with GUVs made of purified Golgi
      lipids, as well as with Golgi membranes. No tube formation was observed when
      kinesins were directly bound to the GUV membrane, suggesting that it is critical
      to distribute the load on both lipids and motors by means of beads. A kinetic
      analysis shows that network growth occurs in two phases: a phase in which
      membrane-bound beads move at the same velocity than free beads, followed by a
      phase in which the tube growth rate decreases and strongly fluctuates. Our work
      demonstrates that the action of motors bound to a lipid bilayer is sufficient to
      generate membrane tubes and opens the way to well controlled experiments aimed at
      the understanding of basic mechanisms in intracellular transport.

PMID- 11959993
TI  - Changes in myosin S1 orientation and force induced by a temperature increase.
AB  - Force generation in myosin-based motile systems is thought to result from an
      angular displacement of the myosin subfragment 1 (S1) tail domain with respect to
      the actin filament axis. In muscle, raised temperature increases the force
      generated by S1, implying a greater change in tail domain angular displacement.
      We used time-resolved x-ray diffraction to investigate the structural corollary
      of this force increase by measuring M3 meridional reflection intensity during
      sinusoidal length oscillations. This technique allows definition of S1
      orientation with respect to the myofilament axis. M3 intensity changes were
      approximately sinusoid at low temperatures but became increasingly distorted as
      temperature was elevated, with the formation of a double intensity peak at
      maximum shortening. This increased distortion could be accounted for by assuming
      a shift in orientation of the tail domain of actin-bound S1 toward the
      orientation at which M3 intensity is maximal, which is consistent with a tail
      domain rotation model of force generation in which the tail approaches a more
      perpendicular projection from the thin filament axis at higher temperatures. In
      power stroke simulations, the angle between S1 tail mean position during
      oscillations and the position at maximum intensity decreased by 4.7 degrees,
      corresponding to a mean tail displacement toward the perpendicular of 0.73 nm for
      a temperature-induced force increase of 0.28 P(0) from 4 to 22 degrees C. Our
      findings suggest that at least 62% of crossbridge compliance is associated with
      the tail domain.

PMID- 11959995
TI  - Modulation of protein translation by Nck-1.
AB  - In mammals, Nck represented by two genes, is a 47-kDa SH2/SH3 domain-containing
      protein lacking intrinsic enzymatic function. Here, we reported that the first
      and the third SH3 domains of Nck-1 interact with the C-terminal region of the
      beta subunit of the eukaryotic initiation factor 2 (eIF2 beta). Binding of eIF2
      beta was specific to the SH3 domains of Nck-1, and in vivo, the interaction
      Nck/eIF2 beta was demonstrated by reciprocal coimmunoprecipitations. In addition,
      Nck was detected in a molecular complex with eIF2 beta in an enriched ribosomal
      fraction, whereas no other SH2/SH3 domain-containing adapters were found. Cell
      fractionation studies demonstrated that the presence of Nck in purified ribosomal
      fractions was enhanced after insulin stimulation, suggesting that growth factors
      dynamically regulate translocation of Nck to ribosomes. In HEK293 cells, we
      observed that transient overexpression of Nck-1 significantly enhanced Cap
      dependent and -independent protein translation. This effect of Nck-1 required the
      integrity of its first and third SH3 domains originally found to interact with
      eIF2 beta. Finally, in vitro, Nck-1 also increased protein translation, revealing
      a direct role for Nck-1 in this process. Our study demonstrates that in addition
      to mediate receptor tyrosine kinase signaling, Nck-1 modulates protein
      translation potentially through its direct interaction with an intrinsic
      component of the protein translation machinery.

PMID- 11959996
TI  - A Los1p-independent pathway for nuclear export of intronless tRNAs in
      Saccharomycescerevisiae.
AB  - Los1p, the Saccharomyces cerevisiae exportin-t homologue, binds tRNA and
      functions in pre-tRNA splicing and export of mature tRNA from the nucleus to the
      cytosol. Because LOS1 is unessential in yeast, other pathways for tRNA nuclear
      export must exist. We report that Cca1p, which adds nucleotides C, C, and A to
      the 3' end of tRNAs, is a multicopy suppressor of the defect in tRNA nuclear
      export caused by los1 null mutations. Mes1p, methionyl-tRNA synthetase, also
      suppresses the defect in nuclear export of tRNA(Met) in los1 cells. Thus, Cca1p
      and Mes1p seem to function in a Los1p-independent tRNA nuclear export pathway.
      Heterokaryon analysis indicates that Cca1p is a nucleus/cytosol-shuttling
      protein, providing the potential for Cca1p to function as an exporter or an
      adapter in this tRNA nuclear export pathway. In yeast, most mutations that affect
      tRNA nuclear export also cause defects in pre-tRNA splicing leading to tight
      coupling of the splicing and export processes. In contrast, we show that
      overexpressed Cca1p corrects the nuclear export, but not the pre-tRNA-splicing
      defects of los1Kan(r) cells, thereby uncoupling pre-tRNA splicing and tRNA
      nuclear export.

PMID- 11959997
TI  - On the mitogenic properties of Rap1b: cAMP-induced G(1)/S entry requires
      activated and phosphorylated Rap1b.
AB  - We have shown that the small GTPase Rap1b, a protein known to antagonize the
      mitogenic and transforming activity of Ras, is endowed with both mitogenic and
      tumorigenic properties. Rap1b can be activated by cAMP, an intracellular message
      known to either stimulate or inhibit cell proliferation. The oncogenic property
      of Rap1b was revealed in a model system in which cAMP stimulates cell
      proliferation and was linked to Rap's ability to promote S phase entry. We have
      now tested the significance of the mitogenic action of Rap1b in a physiologically
      relevant model, the differentiated thyroid follicular cells, a system that
      requires thyroid-stimulating hormone (TSH), acting via cAMP, to mediate a full
      mitogenic response. Here we report that cAMP-dependent hormonal stimulation of
      DNA synthesis requires Rap1b in a manner dependent on its phosphorylation by
      protein kinase A.

PMID- 11959998
TI  - Distinct SNARE complexes mediating membrane fusion in Golgi transport based on
      combinatorial specificity.
AB  - Syntaxin-5 (Sed5) is the only syntaxin needed for transport into and across the
      yeast Golgi, raising the question of how a single syntaxin species could mediate
      vesicle transport in both the anterograde and the retrograde direction within the
      stack. Sed5 is known to combine with two light chains (Bos1 and Sec22) to form
      the t-SNARE needed to receive vesicles from the endoplasmic reticulum. However,
      the yeast Golgi contains several other potential light chains with which Sed5
      could potentially combine to form other t-SNAREs. To explore the degree of
      specificity in the choice of light chains by a t-SNARE, we undertook a
      comprehensive examination of the capacity of all 21 Sed5-based t-SNAREs that
      theoretically could assemble in the yeast Golgi to fuse with each of the 7
      potential v-SNAREs also present in this organelle. Only one additional of these
      147 combinations was fusogenic. This functional proteomic strategy thereby
      revealed a previously uncharacterized t-SNARE in which Sed5 is the heavy chain
      and Gos1 and Ykt6 are the light chains, and whose unique cognate v-SNARE is Sft1.
      Immunoprecipitation experiments confirmed the existence of this complex in vivo.
      Fusion mediated by this second Golgi SNAREpin is topologically restricted, and
      existing genetic and morphologic evidence implies that it is used for transport
      across the Golgi stack. From this study, together with the previous functional
      proteomic analyses which have tested 275 distinct quaternary SNARE combinations,
      it follows that the fusion potential and transport pathways of the yeast cell can
      be read out from its genome sequence according to the SNARE hypothesis with a
      predictive accuracy of about 99.6%.

PMID- 11959999
TI  - Bfa1 can regulate Tem1 function independently of Bub2 in the mitotic exit network
      of Saccharomyces cerevisiae.
AB  - In budding yeast, exit from mitosis is achieved by inactivation of Cdc28/Clb2
      activity. Although it is not clear at present how mitotic exit is triggered, a
      growing body of evidence suggests that the Tem1 GTPase plays a critical role in
      mediating this pathway and that Bfa1 and Bub2 constitute a two-component GTPase
      activating protein to negatively regulate Tem1. Here, we have demonstrated that
      introduction of bfa1 Delta suppresses the growth defects associated with the cdc5
      1 mutation significantly better than that of bub2 Delta, suggesting that Bfa1 may
      have a previously uncharacterized role in this pathway. Overexpression of BFA1
      efficiently arrested the cell cycle at postanaphase even in the absence of BUB2,
      whereas overexpression of BUB2 weakly induced mitotic arrest only in the presence
      of BFA1. Coimmunoprecipitation and in vitro binding studies indicate that Bfa1
      binds strongly to Tem1 independently of Bub2. Provision of GDP+AlF(4)(-), which
      mimics the GTPase transition state, enhanced the Bub2-Tem1 interaction both in
      vitro and in vivo. Interestingly, introduction of bfa1 Delta, but not bub2 Delta,
      greatly increased the interaction between Tem1 and Cdc15, a step that is thought
      to be critical for activating the mitotic exit network. Our data suggest that, in
      addition to its role as a putative, two-component GTPase-activating protein with
      Bub2, Bfa1 also can play a role in the regulation of mitotic exit by directly
      inhibiting the interaction between Tem1 and Cdc15 even in the absence of Bub2.

PMID- 11960000
TI  - Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18
      mSin3 corepressor complex.
AB  - The Suppressor of Fused [Su(fu)] protein plays a conserved role in the regulation
      of Gli transcription factors of the hedgehog (Hh) signaling pathway that controls
      cell fate and tissue patterning during development. In both Drosophila and
      mammals, Su(fu) represses Gli-mediated transcription, but the mode of its action
      is not completely understood. Recent evidence suggests that Su(fu) physically
      interacts with the Gli proteins and, when overexpressed, sequesters Gli in the
      cytoplasm. However, Su(fu) also traverses into the nucleus under the influence of
      a serine-threonine kinase, Fused (Fu), and has the ability to form a DNA-binding
      complex with Gli, suggesting that it has a nuclear function. Here we report that
      the mouse homolog of Su(fu) [mSu(fu)] specifically interacts with SAP18, a
      component of the mSin3 and histone deacetylase complex. In addition, we
      demonstrate that mSu(fu) functionally cooperates with SAP18 to repress
      transcription by recruiting the SAP18-mSin3 complex to promoters containing the
      Gli-binding element. These results provide biochemical evidence that Su(fu)
      directly participates in modulating the transcriptional activity of Gli.

PMID- 11960001
TI  - Xpbx1b and Xmeis1b play a collaborative role in hindbrain and neural crest gene
      expression in Xenopus embryos.
AB  - Pbx1 is a homeodomain protein that functions in complexes with other homeodomain
      containing proteins to regulate gene expression during embryogenesis and
      oncogenesis. Pbx proteins bind DNA cooperatively as heterodimers or higher order
      complexes with Meis family members and Hox proteins and are believed to specify
      cell identity during development. Here, we present evidence that Pbx1, in
      partnership with Meis1b, can regulate posterior neural markers and neural crest
      marker genes during Xenopus development. A Xenopus homolog of the Pbx1b
      homeodomain protein was isolated and shown to be expressed throughout
      embryogenesis. Xpbx1b expression overlaps with Xmeis1 in several areas, including
      the lateral neural folds, caudal branchial arch, hindbrain, and optic cup. When
      ectopically expressed, Xpbx1b can synergize with Xmeis1b to promote posterior
      neural and neural crest gene expression in ectodermal explants. Further, a
      physical interaction between these two homeodomain proteins is necessary for
      induction of these genes in embryonic tissue. In addition, coexpression of
      Xmeis1b and Xpbx1b leads to a prominent shift in the localization of Xmeis1b from
      the cytoplasm to the nucleus, suggesting that nuclear transport or retention of
      Xmeis1b may depend upon Xpbx1b. Finally, expression of a mutant construct in
      which Xpbx1b protein is fused to the repressor domain from Drosophila Engrailed
      inhibits posterior neural and neural crest gene expression. These data indicate
      that Xpbx1b and its partner, Xmeis1b, function in a transcriptional activation
      complex during hindbrain and neural crest development.

PMID- 11960003
TI  - Coping with crowds: density-dependent disease resistance in desert locusts.
AB  - Parasite transmission generally exhibits some form of positive density
      dependence. Thus, as population density increases, so too does the per capita
      risk of becoming infected. Under such circumstances, natural selection should
      favor individuals that use cues associated with population density to determine
      the optimal allocation of resources to disease resistance mechanisms. As a
      consequence, individuals experiencing crowded conditions are predicted to be more
      resistant to parasites and pathogens than those experiencing low-density
      conditions. This phenomenon (termed "density-dependent prophylaxis") [Wilson, K.
      & Reeson, A. F. (1998) Ecol. Entomol. 23, 100-101] is predicted to be
      particularly prevalent in outbreak pest species and in species exhibiting density
      dependent phase polyphenism, such as the desert locust, Schistocerca gregaria.
      Here we show that, as predicted, desert locusts reared under crowded conditions
      are significantly more resistant than solitary locusts to the entomopathogenic
      fungus, Metarhizium anisopliae var. acridum, a key natural disease of acridids
      and an important agent in locust and grasshopper biocontrol. Moreover, enhanced
      pathogen resistance in crowded locusts is associated with elevated antimicrobial
      activity, but not with any difference in thermal preferences or behavioral fever
      response. These results have implications for understanding the development and
      biocontrol of locust plagues.

PMID- 11960002
TI  - A nonsense mutation in zebrafish gata1 causes the bloodless phenotype in vlad
      tepes.
AB  - Vlad tepes (vlt(m651)) is one of only five "bloodless" zebrafish mutants isolated
      through large-scale chemical mutagenesis screening. It is characterized by a
      severe reduction in blood cell progenitors and few or no blood cells at the onset
      of circulation. We now report characterization of the mutant phenotype and the
      identification of the gene mutated in vlt(m651). Embryos homozygous for the
      vlt(m651) mutation had normal expression of hematopoietic stem cell markers
      through 24 h postfertilization, as well as normal expression of myeloid and
      lymphoid markers. Analysis of erythroid development revealed variable expression
      of erythroid markers. Through positional and candidate gene cloning approaches we
      identified a nonsense mutation in the gata1 gene, 1015C --> T (Arg-339 --> Stop),
      in vlt(m651). The nonsense mutation was located C-terminal to the two zinc
      fingers and resulted in a truncated protein that was unable to bind DNA or
      mediate GATA-specific transactivation. A BAC clone containing the zebrafish gata1
      gene was able to rescue the bloodless phenotype in vlt(m651). These results show
      that the vlt(m651) mutation is a previously uncharacterized gata1 allele in the
      zebrafish. The vlt(m651) mutation sheds new light on Gata1 structure and function
      in vivo, demonstrates that Gata1 plays an essential role in zebrafish
      hematopoiesis with significant conservation of function between mammals and
      zebrafish, and offers a powerful tool for future studies of the hematopoietic
      pathway.

PMID- 11960004
TI  - Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at
      low ecologically relevant doses.
AB  - Atrazine is the most commonly used herbicide in the U.S. and probably the world.
      It can be present at several parts per million in agricultural runoff and can
      reach 40 parts per billion (ppb) in precipitation. We examined the effects of
      atrazine on sexual development in African clawed frogs (Xenopus laevis). Larvae
      were exposed to atrazine (0.01-200 ppb) by immersion throughout larval
      development, and we examined gonadal histology and laryngeal size at
      metamorphosis. Atrazine (> or =0.1 ppb) induced hermaphroditism and
      demasculinized the larynges of exposed males (> or =1.0 ppb). In addition, we
      examined plasma testosterone levels in sexually mature males. Male X. laevis
      suffered a 10-fold decrease in testosterone levels when exposed to 25 ppb
      atrazine. We hypothesize that atrazine induces aromatase and promotes the
      conversion of testosterone to estrogen. This disruption in steroidogenesis likely
      explains the demasculinization of the male larynx and the production of
      hermaphrodites. The effective levels reported in the current study are realistic
      exposures that suggest that other amphibian species exposed to atrazine in the
      wild could be at risk of impaired sexual development. This widespread compound
      and other environmental endocrine disruptors may be a factor in global amphibian
      declines.

PMID- 11960006
TI  - Origin of a complex key innovation in an obligate insect-plant mutualism.
AB  - Evolutionary key innovations give organisms access to new ecological resources
      and cause rapid, sometimes spectacular adaptive radiation. The well known
      obligate pollination mutualism between yuccas and yucca moths is a major model
      system for studies of coevolution, and it relies on the key innovation in the
      moths of complex tentacles used for pollen collecting and active pollination.
      These structures lack apparent homology in other insects, making them a rare
      example of a novel limb. We performed anatomical and behavioral studies to
      determine their origin and found evidence of a remarkably simple mechanism.
      Morphological analyses of the tentacles and adjacent mouthparts in pollinators
      and closely related taxa showed that the tentacle appears abruptly in female
      pollinating yucca moths. Several morphological synapomorphies between the galeae,
      which constitute the characteristic lepidopteran proboscis, and the tentacle
      suggest that the tentacle evolved quickly through expression of the genetic
      template for the galea at an apical growth bud on the first segment of the
      maxillary palp. Behavioral data indicate that tentacle and proboscis movements
      are controlled by a shared hydraulic extension mechanism, thus no new mechanism
      was needed for tentacle function. Known developmental paths from other insects
      can explain the origin of this sex-specific key innovation in a few steps.

PMID- 11960005
TI  - In deep trouble: habitat selection constrained by multiple enemies in
      zooplankton.
AB  - Habitat selection behavior is an important predator-avoidance strategy for many
      organisms. Its particular expression is often explained as the result of a
      tradeoff between avoiding antagonists and acquiring resources. However, there is
      need for a broader perspective on this behavior, as organisms are often
      simultaneously involved in complex antagonistic relationships with multiple types
      of enemies. We show experimentally that a tradeoff between predator and parasite
      avoidance may be important in the evolution of habitat selection behavior in the
      waterflea, Daphnia magna. In this species, negatively phototactic clones suffer
      less from visually hunting predators by residing in deeper and darker portions of
      the water column during the day. However, this behavior increases the risk of
      parasitic infections when the Daphnia are exposed to pond sediments containing
      parasite spores. Positively phototactic clones, which are at a higher risk of
      predation, are less exposed to parasite spores in the sediment and consequently
      suffer less from parasitic infection. We show that the increased risk of
      infection remains even if the animals change their phototactic behavior on
      exposure to chemical cues from fish. This tradeoff highlights a substantial cost
      of predator-induced changes in habitat selection behavior. Tradeoffs caused by
      multiple enemies may explain genetic polymorphism for habitat selection behavior
      in many natural populations.

PMID- 11960007
TI  - Evaluating the arrayed primer extension resequencing assay of TP53 tumor
      suppressor gene.
AB  - Identification of mutations in the tumor suppressor gene TP53 has implications
      for the molecular epidemiology and for the molecular pathology of human cancer.
      We have developed and evaluated an arrayed primer extension assay for covering
      both strands of a region of the coding sequence containing more than 95% of the
      mutations described so far in TP53. On average, 97.5% of the arrayed TP53 gene
      sequence can be analyzed from either sense or antisense strands, and 81% from
      both strands. A patient DNA sample is amplified and annealed to arrayed primers,
      which then promote DNA polymerase extension reactions with four fluorescently
      labeled dideoxynucleotides. The TP53 gene chip spans exons 2-9 plus two introns
      from both strands. The performance of the assay was evaluated by using freshly
      extracted genomic DNA, as well as DNA extracted from archival (paraffin-embedded)
      DNA samples. The arrayed primer extension-based TP53 gene test provides an
      accurate and efficient tool for DNA sequence analysis of this frequently mutated
      gene for both research and clinical applications.

PMID- 11960008
TI  - Developmental specificity of recruitment of TBP to the TATA box of the human
      gamma-globin gene.
AB  - It is unclear whether the core promoter is involved in developmental regulation.
      To address this question, we mutated the TATA box of the human gamma-globin gene,
      produced transgenic mice, and examined the effect of the mutation during the
      course of mouse development. In our test system, the gamma-globin gene is
      expressed at similar levels in the embryonic and adult erythroid cells. The TATA
      box mutation dramatically reduced expression of the gamma-globin gene in the
      adult but not in embryonic erythroid cells. In addition, the disruption of the
      gamma TATA box significantly reduced the recruitment of TATA box-binding protein
      (TBP) in the adult cells, but not in embryonic cells, suggesting that the
      recruitment of TBP to the gamma gene promoter is developmentally specific.
      Similarly, the recruitment of transcription factor II B and RNA polymerase II to
      the gamma promoter was affected in the adult but not in embryonic cells. The
      distinct effects of the TATA mutation in the embryonic and adult developmental
      stages suggest that the basal transcription apparatus can be recruited to a core
      promoter in a developmental stage-dependent manner. The TATA mutation resulted in
      a shift of transcription initiation site 6 bp or longer upstream to the cap site
      both in the embryonic and adult erythrocytes. We conclude that the TATA box
      determines the initiation site but not the efficiency of transcription of the
      gamma-globin gene.

PMID- 11960009
TI  - A DNA vector-based RNAi technology to suppress gene expression in mammalian
      cells.
AB  - Double-stranded RNA-mediated interference (RNAi) has recently emerged as a
      powerful reverse genetic tool to silence gene expression in multiple organisms
      including plants, Caenorhabditis elegans, and Drosophila. The discovery that
      synthetic double-stranded, 21-nt small interfering RNA triggers gene-specific
      silencing in mammalian cells has further expanded the utility of RNAi into
      mammalian systems. Here we report a technology that allows synthesis of small
      interfering RNAs from DNA templates in vivo to efficiently inhibit endogenous
      gene expression. Significantly, we were able to use this approach to demonstrate,
      in multiple cell lines, robust inhibition of several endogenous genes of diverse
      functions. These findings highlight the general utility of this DNA vector-based
      RNAi technology in suppressing gene expression in mammalian cells.

PMID- 11960010
TI  - cdk-7 Is required for mRNA transcription and cell cycle progression in
      Caenorhabditis elegans embryos.
AB  - CDK7 is a cyclin-dependent kinase proposed to function in two essential cellular
      processes: transcription and cell cycle regulation. CDK7 is the kinase subunit of
      the general transcription factor TFIIH that phosphorylates the C-terminal domain
      (CTD) of RNA polymerase II, and has been shown to be broadly required for
      transcription in Saccharomyces cerevisiae. CDK7 can also phosphorylate CDKs that
      promote cell cycle progression, and has been shown to function as a CDK
      activating kinase (CAK) in Schizosaccharomyces pombe and Drosophila melanogaster.
      That CDK7 performs both functions in metazoans has been difficult to prove
      because transcription is essential for cell cycle progression in most cells. We
      have isolated a temperature-sensitive mutation in Caenorhabditis elegans cdk-7
      and have used it to analyze the role of cdk-7 in embryonic blastomeres, where
      cell cycle progression is independent of transcription. Partial loss of cdk-7
      activity leads to a general decrease in CTD phosphorylation and embryonic
      transcription, and severe loss of cdk-7 activity blocks all cell divisions. Our
      results support a dual role for metazoan CDK7 as a broadly required CTD kinase,
      and as a CAK essential for cell cycle progression.

PMID- 11960011
TI  - Genes on chromosomes 1 and 13 have significant effects on Ascaris infection.
AB  - Nematode parasites show a characteristic aggregated distribution among hosts.
      This observation has important implications for pathogenesis, immunology, and
      control of these infections, but the relative roles of environment and genetics
      in determining these patterns have remained uncertain. This paper presents the
      results of the first genome scan for susceptibility to infection with roundworm
      (Ascaris lumbricoides). Data on 375 genetic markers were generated for each of
      444 members of a genetically isolated Nepalese population, the Jirels. Ascaris
      worm burden as assessed by egg counts was measured in these same individuals by
      using the Kato Katz thick smear method. The extensive genealogical data available
      for the population allowed assignment of all 444 individuals to a single pedigree
      that contained 6,209 pairs of relatives that were informative for genetic
      analysis. A variance components linkage analysis resulted in the unequivocal
      localization of two genes (one on chromosome 1 and another on chromosome 13) with
      clear, significant effects on susceptibility to Ascaris infection. This is the
      first evidence that individual quantitative trait loci influence variation in
      Ascaris burden in humans.

PMID- 11960012
TI  - T-bet regulates IgG class switching and pathogenic autoantibody production.
AB  - A molecular understanding of the regulation of IgG class switching to IL-4
      independent isotypes, particularly to IgG2a, remains largely unknown. The T-box
      transcription factor T-bet directly regulates Th1 lineage commitment by CD4 T
      cells, but its role in B lymphocytes has been largely unexplored. We show here a
      role for T-bet in the regulation of IgG class switching, especially to IgG2a. T
      bet-deficient B lymphocytes demonstrate impaired production of IgG2a, IgG2b, and
      IgG3 and, most strikingly, are unable to generate germ-line or postswitch IgG2a
      transcripts in response to IFN-gamma. Conversely, enforced expression of T-bet
      initiates IgG2a switching in cell lines and primary cells. This function
      contributes critically to the pathogenesis of murine lupus, where the absence of
      T-bet strikingly reduces B cell-dependent manifestations, including autoantibody
      production, hypergammaglobulinemia, and immune-complex renal disease and, in
      particular, abrogates IFN-gamma-mediated IgG2a production. Classical T cell
      manifestations persisted, including lymphadenopathy and cellular infiltrates of
      skin and liver. These results identify T-bet as a selective transducer of IFN
      gamma-mediated IgG2a class switching in B cells and emphasize the importance of
      this regulation in the pathogenesis of humorally mediated autoimmunity.

PMID- 11960013
TI  - IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase.
AB  - Toll/IL-1 receptor family members are central components of host defense
      mechanisms in a variety of species. One well conserved element in their signal
      transduction is Ser/Thr kinases, which couple early signaling events in a
      receptor complex at the plasma membrane to larger signalosomes in the cytosol.
      The fruit fly Drosophila melanogaster has one member of this family of kinases,
      termed Pelle. The complexity of this pathway is vastly increased in vertebrates,
      and several Pelle homologs have been described and termed IL-1 receptor
      associated kinase (IRAK). Here we report the identification of a novel and
      distinct member of the IRAK family, IRAK-4. IRAK-4 is the closest human homolog
      to Pelle. Endogenous IRAK-4 interacts with IRAK-1 and TRAF6 in an IL-1-dependent
      manner, and overexpression of IRAK-4 can activate NF-kappa B as well as mitogen
      activated protein (MAP) kinase pathways. Most strikingly, and in contrast to the
      other IRAKs, IRAK-4 depends on its kinase activity to activate NF-kappa B. In
      addition, IRAK-4 is able to phosphorylate IRAK-1, and overexpression of dominant
      negative IRAK-4 is blocking the IL-1-induced activation and modification of IRAK
      1, suggesting a role of IRAK-4 as a central element in the early signal
      transduction of Toll/IL-1 receptors, upstream of IRAK-1.

PMID- 11960014
TI  - Amyloid fibers are water-filled nanotubes.
AB  - A study of papers on amyloid fibers suggested to us that cylindrical beta-sheets
      are the only structures consistent with some of the x-ray and electron microscope
      data. We then found that our own 7-year-old and hitherto enigmatic x-ray diagram
      of poly-L-glutamine fits a cylindrical sheet of 31 A diameter made of beta
      strands with 20 residues per helical turn. Successive turns are linked by
      hydrogen bonds between both the main chain and side chain amides, and side chains
      point alternately into and out of the cylinder. Fibers of the exon-1 peptide of
      huntingtin and of the glutamine- and asparagine-rich region of the yeast prion
      Sup35 give the same underlying x-ray diagrams, which show that they have the same
      structure. Electron micrographs show that the 100-A-thick fibers of the Sup35
      peptide are ropes made of three protofibrils a little over 30 A thick. They have
      a measured mass of 1,450 Da/A, compared with 1,426 Da/A for a calculated mass of
      three protofibrils each with 20 residues per helical turn wound around each other
      with a helical pitch of 510 A. Published x-ray diagrams and electron micrographs
      show that fibers of synuclein, the protein that forms the aggregates of Parkinson
      disease, consist of single cylindrical beta-sheets. Fibers of Alzheimer A beta
      fragments and variants are probably made of either two or three concentric
      cylindrical beta-sheets. Our structure of poly-L-glutamine fibers may explain
      why, in all but one of the neurodegenerative diseases resulting from extension of
      glutamine repeats, disease occurs when the number of repeats exceeds 37-40. A
      single helical turn with 20 residues would be unstable, because there is nothing
      to hold it in place, but two turns with 40 residues are stabilized by the
      hydrogen bonds between their amides and can act as nuclei for further helical
      growth. The A beta peptide of Alzheimer's disease contains 42 residues, the best
      number for nucleating further growth. All these structures are very stable; the
      best hope for therapies lies in preventing their growth.

PMID- 11960015
TI  - Aggregation of proteins with expanded glutamine and alanine repeats of the
      glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid beta
      peptide of amyloid plaques.
AB  - The exon-1 peptide of huntingtin has 51 Gln repeats and produces the symptoms of
      Huntington's disease in transgenic mice. Aggregation of the yeast Sup35 protein
      into prions has been attributed to its glutamine-rich and asparagine-rich domain.
      Here, we show that poly-L-asparagine forms polar zippers similar to those of poly
      L-glutamine. In solution at acid pH, the glutamine-rich and asparagine-rich 18
      residue Sup35 peptide, rendered soluble by the addition of two aspartates at the
      amino end and two lysines at the carboxyl end, gives a beta-sheet CD spectrum; it
      aggregates at neutral pH. A poly-alanine peptide D(2)A(10)K(2) gives an alpha
      helical CD spectrum at all pHs and does not aggregate; a peptide with the
      sequence of the C-terminal helix of the alpha-chain of human hemoglobin, preceded
      by two aspartates and followed by two lysines, exhibits a random coil spectrum
      and does not aggregate either. Alignment of several beta-strands with the
      sequence of the 42-residue Alzheimer's amyloid beta-peptide shows that they can
      be linked together by a network of salt bridges. We also asked why single amino
      acid replacements can so destabilize the native structures of proteins that they
      unfold and form amyloids. The difference in free energy of a protein molecule
      between its native, fully ordered structure and an amorphous mixture of randomly
      coiled chains is only of the order of 10 kcal/mol. Theory shows that
      destabilization of the native structure by no more than 2 kcal/mol can increase
      the probability of nucleation of disordered aggregates from which amyloids could
      grow 130,000-fold.

PMID- 11960016
TI  - Overexpression of the cytotoxic T cell GalNAc transferase in skeletal muscle
      inhibits muscular dystrophy in mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is a congenital X-linked myopathy caused by
      lack of dystrophin protein expression. In DMD, the expression of many dystrophin
      associated proteins (DAPs) is reduced along the sarcolemmal membrane, but the
      same proteins remain concentrated at the neuromuscular junction where utrophin, a
      dystrophin homologue, is expressed [Matsumura, K., Ervasti, J. M., Ohlendieck,
      K., Kahl, K. D. & Campbell, K. (1992) Nature (London) 360, 588-591]. This outcome
      has led to the concept that ectopic expression of a "synaptic scaffold" of DAPs
      and utrophin along myofibers might compensate for the molecular defects in DMD.
      Here we show that transgenic overexpression of the synaptic CT GalNAc transferase
      in the skeletal muscles of mdx animals (mdx/CT) increases the expression of
      utrophin and many DAPs, including dystroglycans, sarcoglycans, and dystrobrevins,
      along myofibers. Protein expression of utrophin and DAPs was equal to or above
      that of wild-type mice. In addition, alpha-dystroglycan was glycosylated with the
      CT carbohydrate antigen in mdx/CT but not in mdx muscles. mdx/CT mice have little
      or no evidence of muscular dystrophy by several standard measures; Serum creatine
      kinase levels, percentage of centrally located myofiber nuclei, and variance in
      myofiber diameter in mdx/CT muscles were dramatically reduced compared with mdx
      mice. These data suggest that ectopic expression of the CT GalNAc transferase
      creates a functional dystrophin-related complex along myofibers in the absence of
      dystrophin and should be considered as a target for therapeutic intervention in
      DMD.

PMID- 11960017
TI  - Gating the bacterial mechanosensitive channel MscL invivo.
AB  - YggB and MscL are the major mechanosensitive channels in Escherichia coli, and
      each can rescue the double knockout mutant from osmotic downshock. However, the
      role of MscL in wild-type bacteria is in question, not only because cells without
      MscL survive severe osmotic downshocks, but because 1.8 times more suction is
      required to gate MscL than YggB under patch clamp. Here, we extend previous
      evidence [Ajouz, B., Berrier, C., Garrigues, A., Besnard, M. & Ghazi, A. (1998)
      J. Biol. Chem. 273, 26670-26674] to show that downshock gates MscL in vivo even
      in the presence of YggB. We have made this determination by engineering a channel
      we can structurally modify in vivo (Leu-19-->Cys MscL). MscLs with charges in
      their constrictions are known to open easily and transiently to substates and
      stop cell growth. In this study, we use downshock to stretch this region open to
      allow attachment of a charged thiosulfonate reagent MTSET(+), thereby creating a
      toxic channel. Therefore, channel opening can be monitored by loss of colony
      forming units. By this measure, we find that an approximately 800 mmol/kg
      downshock from 1,200 mmol/kg medium opens Leu-19-->Cys MscL in the presence of
      YggB, but a downshock of only approximately 400 mmol/kg is required in the
      absence of YggB. In parallel, Leu-19-->Cys MscL, stretched open by large
      sustained suction in the presence of MTSET(+) in voltage-clamped patches,
      subsequently flickers open with little suction. These observations show that MscL
      opening is triggered by a specific downshock, even in the presence of YggB, that
      YggB buffers MscL gating in vivo, and that residue 19 becomes exposed upon
      channel opening.

PMID- 11960018
TI  - Differential activation of the human orbital, mid-ventrolateral, and mid
      dorsolateral prefrontal cortex during the processing of visual stimuli.
AB  - There is considerable uncertainty about the precise functional contribution of
      the different parts of the prefrontal cortex to mnemonic processing. Changes in
      regional cerebral blood flow were measured with positron emission tomography in
      normal human subjects exposed to abstract visual designs under various
      conditions. It was demonstrated that the processing of stimuli that deviate from
      expectations involves selectively the orbitofrontal cortex, namely the part of
      the frontal cortex that is preferentially linked with the limbic system. By
      contrast, when the subject is making an explicit decision on the contents of
      memory (e.g., judgments of relative stimulus familiarity), the mid-ventrolateral
      prefrontal cortex is involved. The mid-dorsolateral prefrontal cortex is engaged
      when monitoring of information within working memory is required.

PMID- 11960019
TI  - Perception of biological motion without local image motion.
AB  - A vivid perception of the moving form of a human figure can be obtained from a
      few moving light points on the joints of the body. This is known as biological
      motion perception. It is commonly believed that the perception of biological
      motion rests on image motion signals. Curiously, however, some patients with
      lesions to motion processing areas of the dorsal stream are severely impaired in
      image motion perception but can easily perceive biological motion. Here we
      describe a biological motion stimulus based on a limited lifetime technique that
      tests the perception of a moving human figure in the absence of local image
      motion. We find that subjects can spontaneously recognize a moving human figure
      in displays without local image motion. Their performance is very similar to that
      for classic point-light displays. We also find that tasks involving the
      discrimination of walking direction or the coherence of a walking figure can be
      performed in the absence of image motion. Thus, although image motion may
      generally aid processes such as segmenting figure from background, we propose
      that it is not the basis for the precept of biological motion. Rather, we suggest
      biological motion is derived from dynamic form information on body posture
      evolving over time.

PMID- 11960020
TI  - Fighting fruit flies: a model system for the study of aggression.
AB  - Despite the importance of aggression in the behavioral repertoire of most
      animals, relatively little is known of its proximate causation and control. To
      take advantage of modern methods of genetic analysis for studying this complex
      behavior, we have developed a quantitative framework for studying aggression in
      common laboratory strains of the fruit fly, Drosophila melanogaster. In the
      present study we analyze 73 experiments in which socially naive male fruit flies
      interacted in more than 2,000 individual agonistic interactions. This allows us
      to (i) generate an ethogram of the behaviors that occur during agonistic
      interactions; (ii) calculate descriptive statistics for these behaviors; and
      (iii) identify their temporal patterns by using sequence analysis. Thirty-minute
      paired trials between flies contained an average of 27 individual agonistic
      interactions, lasting a mean of 11 seconds and featuring a variety of intensity
      levels. Only few fights progressed to the highest intensity levels (boxing and
      tussling). A sequential analysis demonstrated the existence of recurrent patterns
      in behaviors with some similarity to those seen during courtship. Based on the
      patterns characterized in the present report, a detailed examination of
      aggressive behavior by using mutant strains and other techniques of genetic
      analysis becomes possible.

PMID- 11960021
TI  - The neural system that bridges reward and cognition in humans: an fMRI study.
AB  - We test the hypothesis that motivational and cognitive processes are linked by a
      specific neural system to reach maximal efficiency. We studied six normal
      subjects performing a working memory paradigm (n-back tasks) associated with
      different levels of monetary reward during an fMRI session. The study showed
      specific brain activation in relation with changes in both the cognitive loading
      and the reward associated with task performance. First, the working memory tasks
      activated a network including the dorsolateral prefrontal cortex [Brodmann area
      (BA) 9/46] and, in addition, in the lateral frontopolar areas (BA 10), but only
      in the more demanding condition (3-back task). This result suggests that lateral
      prefrontal areas are organized in a caudo-rostral continuum in relation with the
      increase in executive requirement. Second, reward induces an increased activation
      in the areas already activated by working memory processing and in a
      supplementary region, the medial frontal pole (BA 10), regardless of the level of
      cognitive processing. It is postulated that the latter region plays a specific
      role in monitoring the reward value of ongoing cognitive processes. Third, we
      detected areas where the signal decreases (ventral-BA 11/47 and subgenual
      prefrontal cortices) in relation with both the increase of cognitive demand and
      the reward. The deactivation may represent an emotional gating aimed at
      inhibiting adverse emotional signals to maximize the level of performance. Taken
      together, these results suggest a balance between increasing activity in cortical
      cognitive areas and decreasing activity in the limbic and paralimbic structures
      during ongoing higher cognitive processing.

PMID- 11960022
TI  - Filamentous phage as vector-mediated antibody delivery to the brain.
AB  - Early diagnosis of Alzheimer's disease is prevented by lack of means to visualize
      and target beta amyloid plaques in the brains of affected people. There are many
      methods of detecting amyloid plaques by staining postmortem brain tissue, but
      none are available for monitoring in living patients. We propose anti-beta
      amyloid antibodies as a highly specific probe to monitor amyloid plaque formation
      in living patients. Intranasal administration of filamentous phage as delivery
      vector of anti-beta amyloid antibody fragment into Alzheimer's APP transgenic
      mice enables in vivo targeting of beta amyloid plaques. The plaques were co
      visualized both by thioflavin-S and fluorescent-labeled anti-phage antibodies in
      the olfactory bulb and the hippocampus region. The genetically engineered
      filamentous bacteriophage proved to be an efficient and nontoxic viral delivery
      vector to the brain, offering an obvious advantage over other mammalian vectors.
      The ability to image A beta deposits in vivo would arguably provide the most
      useful diagnostic and monitoring test for early diagnosis of Alzheimer's disease.

PMID- 11960023
TI  - Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A
      dependent manner.
AB  - Several ion channels and pumps are regulated by syntaxin 1A, a component of the
      synaptic vesicle docking and fusion apparatus. One such regulated protein is the
      rat brain gamma-aminobutyric acid (GABA) transporter GAT1. The N-terminal
      cytoplasmic domain of GAT1 directly interacts with syntaxin 1A; this interaction
      induces a decrease in the rate at which GABA and associated ions are transported.
      GAT1 function also is regulated by transporter substrates, raising the
      possibility that substrates mediate at least some of their effects by regulating
      the interaction between GAT1 and syntaxin 1A. In oocytes expressing GAT1 and
      syntaxin 1A, superfusion of transporter substrates increases the GAT1 transport
      rate. The substrate-induced rate change (i) is prevented by coapplication of GAT1
      antagonists, (ii) does not occur in oocytes expressing GAT1 alone, and (iii) does
      not occur in oocytes expressing interaction-deficient syntaxin 1A mutants. In
      oocytes, and in hippocampal neurons that endogenously express both GAT1 and
      syntaxin 1A, substrate application results in a decrease in the fraction of
      syntaxin 1A that is bound to GAT1 on a time-scale comparable to the substrate
      induced change in transport rates. These data suggest that substrate
      translocation regulates GAT1-syntaxin 1A interactions and provide a mechanism by
      which GABA transport can be increased during times of rising synaptic GABA
      concentrations.

PMID- 11960024
TI  - Progressive photoreceptor degeneration, outer segment dysplasia, and rhodopsin
      mislocalization in mice with targeted disruption of the retinitis pigmentosa-1
      (Rp1) gene.
AB  - Retinitis pigmentosa (RP), a common group of human retinopathic diseases, is
      characterized by late-onset night blindness, loss of peripheral vision, and
      diminished or absent electroretinogram (ERG) responses. Mutations in the
      photoreceptor-specific gene RP1 account for 5-10% of cases of autosomal dominant
      RP. We generated a mouse model of the RP1 form of RP by targeted disruption of
      the mouse ortholog (Rp1) of human RP1. In Rp1(-/-) mice, the number of rod
      photoreceptors decreased progressively over a period of 1 year, whereas that of
      cone photoreceptors did not change for at least 10 months. Light and electron
      microscopic analysis revealed that outer segments of Rp1(-/-) rods and cones were
      morphologically abnormal and became progressively shorter in length. Before
      photoreceptor cell death, rhodopsin was mislocalized in inner segments and cell
      bodies of Rp1(-/-) rods. Rod ERG amplitudes of Rp1(-/-) mice were significantly
      smaller than those of Rp1(+/+) mice over a period of 12 months, whereas those of
      Rp1(+/-) mice were intermediate. The decreases in cone ERG amplitudes were slower
      and less severe than those in rods. These findings demonstrate that Rp1 is
      required for normal morphogenesis of photoreceptor outer segments and also may
      play a role in rhodopsin transport to the outer segments. The phenotype of Rp1
      mutant mice resembles the human RP1 disease. Thus, these mice provide a useful
      model for studies of RP1 function, disease pathology, and therapeutic
      interventions.

PMID- 11960025
TI  - Identification of genes expressed with temporal-spatial restriction to developing
      cerebellar neuron precursors by a functional genomic approach.
AB  - Hedgehog pathway activation is required for proliferation of cerebellar granule
      cell neuron precursors during development and is etiologic in certain cerebellar
      tumors. To identify genes expressed specifically in granule cell neuron
      precursors, we used oligonucleotide microarrays to analyze regulation of 13,179
      genes/expressed sequence tags in heterogeneous primary cultures of neonatal mouse
      cerebellum that respond to the mitogen Sonic hedgehog. In conjunction, we applied
      experiment-specific noise models to render a gene-by-gene robust indication of up
      regulation in Sonic hedgehog-treated cultures. Twelve genes so identified were
      tested, and 10 (83%) showed appropriate expression in the external granular layer
      (EGL) of the postnatal day (PN) 7 cerebellum and down-regulation by PN 15, as
      verified by in situ hybridization. Whole-organ profiling of the developing
      cerebellum was carried out from PN 1 to 30 to generate a database of temporal
      gene regulation profiles (TRPs). From the database an algorithm was developed to
      capture the TRP typical of EGL-specific genes. The "TRP-EGL" accurately predicted
      expression in vivo of an additional 18 genes/expressed sequence tags with a
      sensitivity of 80% and a specificity of 88%. We then compared the positive
      predictive value of our analytical procedure with other widely used methods, as
      verified by the TRP-EGL in silico. These findings suggest that replicate
      experiments and incorporation of noise models increase analytical specificity.
      They further show that genome-wide methods are an effective means to identify
      stage-specific gene expression in the developing granule cell lineage.

PMID- 11960026
TI  - Supercool or dehydrate? An experimental analysis of overwintering strategies in
      small permeable arctic invertebrates.
AB  - Soil invertebrate survival in freezing temperatures has generally been considered
      in the light of the physiological adaptations seen in surface living insects.
      These adaptations, notably the ability to supercool, have evolved in concert with
      surface invertebrates' ability to retain body water in a dry environment.
      However, most soil invertebrates are orders of magnitude less resistant to
      desiccation than these truly terrestrial insects, opening the possibility that
      the mechanisms involved in their cold-hardiness are also of a radically different
      nature. Permeable soil invertebrates dehydrate when exposed in frozen soil. This
      dehydration occurs because the water vapor pressure of supercooled water is
      higher than that of ice at the same temperature. The force of this vapor pressure
      difference is so large that even a few degrees of supercooling will result in
      substantial water loss, continuing until the vapor pressure of body fluids equals
      that of the surrounding ice. At this stage, the risk of tissue ice formation has
      been eliminated, and subzero survival is ensured. Here we show that these soil
      invertebrates do not base their winter survival on supercooling, as do many other
      ectotherms, but instead dehydrate and equilibrate their body-fluid melting point
      to the ambient temperature. They can achieve this equilibration even at the
      extreme cooling rates seen in polar soils.

PMID- 11960027
TI  - Resting and circadian release of nitric oxide is controlled by leptin in male
      rats.
AB  - Because leptin stimulates nitric oxide (NO) release from the hypothalamus and
      anterior pituitary gland, we hypothesized that it also might release NO from
      adipocytes, the principal source of leptin. Consequently, plasma concentrations
      of leptin and NO, estimated from its metabolites NO(3) and NO(2) (NO(3)-NO(2)),
      were measured in adult male rats. There was a linear increase of both leptin and
      NO(3)-NO(2) with body weight that was associated with a parallel rise in fat
      mass. These findings indicate that release of leptin and NO is directly related
      to adipocyte mass. Furthermore, there was a parallelism in circadian rhythm of
      both substances, with peaks at 0130 h and nadirs at 0730 h. Measurement of both
      leptin and NO(3)-NO(2) in plasma from individual rats revealed that NO(3)-NO(2)
      increased linearly with leptin. Incubation of epididymal fat pads with leptin or
      its i.v. injection in conscious rats increased NO(3)-NO(2) release. The release
      of NO(3)-NO(2) in vivo and in vitro exceeded that of leptin by many fold,
      indicating that leptin activates NO synthase. Leptin increased tumor necrosis
      factor (TNF)-alpha release at a 100-fold lower dose than required for NO release
      in vitro and in vivo, suggesting that it also may participate in leptin-induced
      NO release. However, because many molecules of leptin were required to release a
      molecule of TNF-alpha in vivo and in vitro, we believe that leptin-induced TNF
      alpha release is an associated phenomenon not involved in NO production. The
      results support the hypothesis that adipocytes play a major role in NO release by
      activating NO synthase in the adipocytes and the adjacent capillary endothelium.

PMID- 11960028
TI  - A dynamin-like protein (ADL2b), rather than FtsZ, is involved in Arabidopsis
      mitochondrial division.
AB  - Recently, the FtsZ protein, which is known as a key component in bacterial cell
      division, was reported to be involved in mitochondrial division in algae. In
      yeast and animals, however, mitochondrial fission depends on the dynamin-like
      proteins Dnm1p and Drp1, respectively, whereas in green plants, no potential
      mitochondrial division genes have been identified. BLAST searches of the nuclear
      and mitochondrial genome sequences of Arabidopsis thaliana did not find any
      obvious homologue of the alpha-proteobacterial-type ftsZ genes. To determine
      whether mitochondrial division of higher plants depends on a dynamin-like
      protein, we cloned a cDNA for ADL2b, an Arabidopsis homologue of Dnm1p, and
      tested its subcellular localization and its dominant-negative effect on
      mitochondrial division. The fusion protein of green fluorescent protein and ADL2b
      was observed as punctate structures localized at the tips and at the constriction
      sites of mitochondria in live plant cells. Cells expressing dominant-negative
      mutant ADL2b proteins (K56A and T77F) showed a significant fusion, aggregation,
      and/or tubulation of mitochondria. We propose that mitochondrial division in
      higher plants is conducted by dynamin-like proteins similar to ADL2b in
      Arabidopsis. The evolutional points of loss of mitochondrial FtsZ and the
      functional acquisition of dynamin-like proteins in mitochondrial division are
      discussed.

PMID- 11960030
TI  - Individual differences versus social dynamics in the formation of animal
      dominance hierarchies.
AB  - Linear hierarchies, the classical pecking-order structures, are formed readily in
      both nature and the laboratory in a great range of species including humans.
      However, the probability of getting linear structures by chance alone is quite
      low. In this paper we investigate the two hypotheses that are proposed most often
      to explain linear hierarchies: they are predetermined by differences in the
      attributes of animals, or they are produced by the dynamics of social
      interaction, i.e., they are self-organizing. We evaluate these hypotheses using
      cichlid fish as model animals, and although differences in attributes play a
      significant part, we find that social interaction is necessary for high
      proportions of groups with linear hierarchies. Our results suggest that dominance
      hierarchy formation is a much richer and more complex phenomenon than previously
      thought, and we explore the implications of these results for evolutionary
      biology, the social sciences, and the use of animal models in understanding human
      social organization.

PMID- 11960031
TI  - Images in endoscopy: ascites with pseudocysts in a woman with Chlamydia
      trachomatis infection of the pelvis.

PMID- 11960029
TI  - Arabidopsis disrupted in SQD2 encoding sulfolipid synthase is impaired in
      phosphate-limited growth.
AB  - The sulfolipid sulfoquinovosyldiacylglycerol is one of the three nonphosphorous
      glycolipids that provide the bulk of the structural lipids in photosynthetic
      membranes of seed plants. Unlike the galactolipids, sulfolipid is anionic at
      physiological pH because of its 6-deoxy-6-sulfonate-glucose (sulfoquinovose) head
      group. The biosynthesis of this lipid proceeds in two steps: first, the assembly
      of UDP-sulfoquinovose from UDP-glucose and sulfite, and second, the transfer of
      the sulfoquinovose moiety from UDP-sulfoquinovose to diacylglycerol. The first
      reaction is catalyzed by the SQD1 protein in Arabidopsis. Here we describe the
      identification of the SQD2 gene of Arabidopsis. We propose that this gene encodes
      the sulfoquinovosyltransferase catalyzing the second step of sulfolipid
      biosynthesis. Expression of SQD1 and SQD2 in Escherichia coli reconstituted plant
      sulfolipid biosynthesis in this bacterium. Insertion of a transfer DNA into this
      gene in Arabidopsis led to complete lack of sulfolipid in the respective sqd2
      mutant. This mutant showed reduced growth under phosphate-limited growth
      conditions. The results support the hypothesis that sulfolipid can function as a
      substitute of anionic phospholipids under phosphate-limited growth conditions.
      Along with phosphatidylglycerol, sulfolipid contributes to maintaining a
      negatively charged lipid-water interface, which presumably is required for proper
      function of photosynthetic membranes.

PMID- 11960032
TI  - Images in endoscopy: tubal torsion with severe congestion managed
      laparoscopically.

PMID- 11960033
TI  - Routine clinical examination is not sufficient for diagnosing and locating deeply
      infiltrating endometriosis.
AB  - STUDY OBJECTIVE: To determine whether routine clinical examination is sufficient
      for the diagnosis and establishing the location of deeply infiltrating
      endometriosis (DIE). DESIGN: Retrospective analysis (Canadian Task Force
      classification II-2). SETTING: University-affiliated hospital. Patients. One
      hundred sixty women with histologically proved deeply infiltrating endometriosis.
      MEASUREMENTS AND MAIN RESULTS: Speculum examination allowed endometriotic lesions
      to be viewed in only 14.4% (23) of patients, and a classic, painful, spheric
      nodule was palpated in only 43.1% (69). Results of routine clinical examination
      varied significantly with location of DIE. Whereas a nodule was found in 80.0%
      (24) of patients with vaginal endometriosis, this rate dropped to only 35.3% (6)
      and 33.3% (34) in those with DIE of the digestive tract and uterosacral
      ligaments, respectively (p <0.0001). CONCLUSION: High locations of DIE lesions at
      the level of uterosacral ligaments, bottom of the pouch of Douglas, and upper one
      third of the posterior vaginal wall explain why results of routine clinical
      examination are so poor. The term "deep endometriosis infiltrating the
      rectovaginal septum" is generally incorrect in the true anatomic sense.

PMID- 11960034
TI  - Cost analysis of tubal anastomosis by laparoscopy and by laparotomy.
AB  - STUDY OBJECTIVE: To compare the costs of tubal anastomosis performed by
      laparoscopy and by laparotomy. DESIGN: Cost analysis study using the hospital
      administrative database (Canadian Task Force classification II-2). SETTING:
      University teaching hospital. PATIENTS: Eighty-nine women. Intervention. Tubal
      anastomosis by laparoscopy (43) and by laparotomy (46). MEASUREMENTS AND MAIN
      RESULTS: Tubal anastomosis took longer when performed by laparoscopy than by
      laparotomy; however, the total time patients spent in the operating room was
      similar. Women treated by laparoscopy spent more time in the recovery room. Labor
      costs for nurses in the operating room and recovery room costs were significantly
      higher in the laparoscopy group. Costs for operating room supplies were similar.
      Pharmacy costs and expenses in the ward were lower in the laparoscopy group. The
      mean total cost for laparoscopic tubal anastomosis was $861 +/- 137 and for
      laparotomy was $1348 +/- 188 (p <0.001). CONCLUSION: Laparoscopic tubal
      anastomosis costs less than tubal anastomosis by laparotomy.

PMID- 11960035
TI  - Total laparoscopic hysterectomy for very enlarged uteri.
AB  - STUDY OBJECTIVE: To evaluate short-term outcome of total laparoscopic
      hysterectomy (TLH) performed in women with very enlarged uteri. DESIGN: Case
      control study (Canadian Task Force classification II-2). SETTING: Hospital
      gynecologic service. PATIENTS: Thirty-four consecutive women with very enlarged
      uteri. INTERVENTION: Total laparoscopic hysterectomy for benign pathology.
      MEASUREMENTS AND MAIN RESULTS: Women with uterine enlargement (group 1) were
      compared with 68 women with uteri weighing 300 g or less (group 2) who underwent
      TLH during the same period. Matching was based on patient age +/- 2 years,
      surgeon (experienced senior, fellow), whether or not Burch operation was
      performed, and whether or not adnexectomy was performed. The groups were compared
      for complication rates, operating time, hospital stay, change in perioperative
      hemoglobin concentration, and vaginal and laparoscopic uterine morcellation. They
      did not differ statistically significantly in terms of indications for surgery,
      parity, postmenopausal status, and preoperative hemoglobin levels. No difference
      was seen in complication rates between groups. Operating time was significantly
      shorter (p <0.001) in women with smaller uteri than in those with very enlarged
      uteri, 108 +/- 35 and 156 +/- 50 minutes, respectively. The groups did not differ
      significantly in day 1 hemoglobin level drop, analgesia requirement (oral,
      intravenous opioid), time to passing gas and stool, or hospital stay. No
      conversion to laparotomy was required in either group. CONCLUSION: A very
      enlarged uterus should not be considered a contraindication for TLH. However, it
      may be necessary to undertake certain surgical steps to ensure optimal exposure
      of the operative field and more effective and safer excision of the uterine
      vascular pedicle.

PMID- 11960036
TI  - Resectoscopic surgery in women with abnormal uterine bleeding and nonatypical
      endometrial hyperplasia.
AB  - STUDY OBJECTIVE: To evaluate the role of resectoscopic surgery in the diagnosis
      and treatment of women with abnormal uterine bleeding and endometrial hyperplasia
      without atypia. DESIGN: Retrospective analysis (Canadian Task Force
      classification II-2). SETTING: University-affiliated teaching hospital. PATIENTS:
      Twenty-five women with simple and seven with complex hyperplasia. INTERVENTION:
      Hysteroscopic endometrial ablation. MEASUREMENTS AND MAIN RESULTS: In patients
      with simple hyperplasia, average age, parity, body mass index, and mean arterial
      pressure were 53.2 years, 2.4 pregnancies, 30 kg/m2, and 99.5 mm Hg,
      respectively; in those with complex hyperplasia corresponding figures were 48
      years, 2 pregnancies, 36 kg/m2, and 100 mm Hg. Nineteen of 32 women had
      postmenopausal bleeding, 9 of whom were taking combined hormone replacement
      therapy. Two had subsequent hysterectomies, one for pain and the other for
      incomplete resection due to an enlarged uterus. Resection could not be completed
      in one morbidly obese woman. One patient died from heart disease. During the
      follow-up of 1 to 8 years (mean 4 yrs) all patients remained amenorrheic with no
      evidence of recurrent disease or progression to cancer. CONCLUSION: Resectoscopic
      surgery by experienced hysteroscopists may be effective therapy for endometrial
      hyperplasia without atypia, especially in women at high risk for medical therapy
      or hysterectomy. Patient surveillance is mandatory for early detection and
      management of recurrent disease and progression to cancer.

PMID- 11960037
TI  - Resectoscopic surgery in 10 women with abnormal uterine bleeding and atypical
      endometrial hyperplasia.
AB  - STUDY OBJECTIVE: To evaluate the role of the resectoscope in the diagnosis and
      treatment of women with abnormal uterine bleeding (AUB) and atypical endometrial
      hyperplasia. DESIGN: Retrospective case series (Canadian Task Force
      classification III-3). SETTING: University-affiliated teaching hospital.
      PATIENTS: Ten women. Intervention. Hysteroscopic evaluation after preoperative
      endometrial biopsy indicated simple hyperplasia without atypia, complex
      hyperplasia with atypia, or inadequate specimen. MEASUREMENTS AND MAIN RESULTS:
      Atypical hyperplasia was confirmed in eight patients after total endomyometrial
      resection. Hysterectomy was offered to all patients but accepted by only two: one
      for bilateral ovarian serous cystadenomas and the second for a granulosa cell
      ovarian tumor. No residual endometrium was found in hysterectomy specimens. Seven
      women were amenorrheic and well 1 to 9 years after resection. An additional
      patient with amenorrhea died from colon cancer 2 years after resection.
      CONCLUSION: Resectoscopic surgery confirmed or detected atypical endometrial
      hyperplasia in eight women and excluded it in two patients with AUB and a
      previous diagnosis of simple hyperplasia, atypical hyperplasia, or inadequate
      specimen. Skillful resectoscopic surgery may be an alternative to hysterectomy in
      selected patients with atypical hyperplasia who are compliant with regular and
      long-term follow-up.

PMID- 11960038
TI  - Laparoscopic findings, management, histopathology, and outcome of 25 women with
      cyclic leg pain.
AB  - STUDY OBJECTIVE: To determine pelvic findings, histopathology, and clinical
      outcome in women with chronic pelvic pain and cyclic sciatica-like pain after
      laparoscopic surgery. DESIGN: Retrospective cohort study (Canadian Task Force
      classification II-2). SETTING: University-affiliated teaching hospital. PATIENTS:
      Of 2115 women with chronic pelvic pain, 25 also complained of cyclic pain
      radiating to the leg (right 15, left 9, both 1), pain over buttocks, and
      paresthesia of the thighs and/or knees, exacerbated during menses. INTERVENTION:
      Laparoscopy. MEASUREMENTS AND MAIN RESULTS: Laparoscopic findings were
      endometriosis nodules (5 patients), peritoneal pockets and/or peritoneal
      endometriosis (19), and inflammatory peritoneum (1). Associated pelvic
      endometriosis was identified and confirmed in 17 women (68%). No additional
      lesions other than peritoneal pockets were found in eight (32%). All nodules,
      peritoneal pockets, and abnormal peritoneum were excised with a combination of
      hydrodissection and carbon dioxide laser. Peritoneum over resultant deep defects
      was sutured with one to three 2-0 nonabsorbable sutures in accordance with the
      surgeon's practice and experience. Endometriosis was confirmed in all five
      nodules, and histology of excised pockets showed endometriosis in nine (60.0%),
      endosalpingiosis in two (13.3%), chronic inflammation in one (6.7%), and normal
      tissue in three (20.0%). After laparoscopic excision sciatic symptoms were
      eliminated in 19, markedly improved in 4, remained the same in 2, and recurred in
      3 patients after 2 years. CONCLUSION: Cyclic leg signs and symptoms were
      associated with pelvic peritoneal pockets, endometriosis nodules, or surface
      endometriosis of the posterolateral pelvic peritoneum. We hypothesize that the
      pain associated with these lesions is more likely referred pain originating from
      pelvic peritoneum than direct irritation of the lumbosacral plexus of the sciatic
      nerve.

PMID- 11960039
TI  - Comparison of laparoscopy and laparotomy in patients with endometrial cancer.
AB  - STUDY OBJECTIVE: To evaluate results and feasibility of laparoscopic surgery in
      patients with stage I endometrial cancer. DESIGN: Prospective, nonrandomized
      study (Canadian Task Force classification II-I). SETTING: University tertiary
      referring center. PATIENTS: Fifty-one women with stage I endometrial cancer
      followed for 1 year. INTERVENTION: Laparoscopy (27 women) and open surgery (24).
      MEASUREMENTS AND MAIN RESULTS: We recorded operating time, complications, and
      length of hospital stay. Operating time differed between groups, 87 versus 143
      minutes for laparotomy and laparoscopy, respectively. Hospital stay was 6.2 days
      and 4.3 days, respectively. In the laparotomy group one patient experienced wound
      dehiscence and another had a vesicovaginal fistula requiring secondary repair.
      Complications in the laparoscopy group were one conversion to laparotomy because
      of bladder perforation and one case of septicemia that required laparotomy on the
      second postoperative day. Perioperative transfusions were administered to two
      women in the laparotomy group and none in the laparoscopy group. CONCLUSION:
      Laparoscopy may play an important role in treatment of early endometrial cancer.
      The procedure is difficult, however, and should be reserved to dedicated
      laparoscopists. It has low morbidity and, contrary to earlier recommendations,
      may be performed in older women with comorbidity.

PMID- 11960041
TI  - Relationship between obesity and the risk of gynecologic laparoscopy in Korean
      women.
AB  - STUDY OBJECTIVE: To determine whether obesity increases risk of performing
      laparoscopic gynecologic surgery in Korean women. DESIGN: Retrospective analysis
      over 35 consecutive months (Canadian Task Force classification II-2). SETTING:
      University-affiliated hospital. PATIENTS: Two hundred seventy-seven women who
      underwent gynecologic laparoscopic surgery. INTERVENTION: Patients were analyzed
      by chart review. MEASUREMENTS AND MAIN RESULTS: Obesity was defined as body mass
      index (BMI) 25 kg/m(2) or greater. Patients were categorized on the basis of BMI
      [weight (kg)/height(2) (m(2))] as obese (BMI > or =25, 74 women) or nonobese (BMI
      < 25, 203). Each group was further divided into three subgroups according to
      operation difficulty. No significant differences in patient age, parity,
      menopausal status, medicosurgical illness, or history of intraabdominal surgery
      were apparent between groups, except for distribution of operation difficulty and
      adhesion grade; however, the adhesion grade was evenly distributed in each
      operation grade subgroup. In the two BMI groups, no significant differences were
      seen in surgical values (estimated blood loss, operating time, operative
      complications, postoperative complications, hospital stay, rate of conversion to
      laparotomy). CONCLUSION: Obesity had generally been thought to increase the risk
      of laparoscopic surgery. In our study in obese Korean women, however, it did not
      seem to increase the risk, and gynecologic laparoscopic surgery was performed
      safely.

PMID- 11960040
TI  - Perceived proficiency in endoscopic techniques among senior obstetrics and
      gynecology residents.
AB  - STUDY OBJECTIVES: To assess current training methods in laparoscopic surgery
      employed in United States obstetrics and gynecology residency programs, level of
      proficiency in various minimally invasive surgery procedures amongst senior
      obstetrics and gynecology residents, and ways in which training in minimally
      invasive surgery can be improved. DESIGN: Survey (Canadian Task Force
      classification III). SETTING: Accredited obstetrics and gynecology programs in
      the United States. SUBJECTS: All fourth-year residents in accredited obstetrics
      and gynecology programs in the United States. INTERVENTION: Residents received a
      survey regarding their perceived proficiency performing various laparoscopic
      procedures and the type of training they received in these techniques.
      MEASUREMENTS AND MAIN RESULTS: Responses were received from 133 programs (52.4%)
      and 295 residents (26.8%). Of these, 67% of residents thought emphasis on
      laparoscopic surgery training should be increased or greatly increased; 87%
      thought laparoscopic skills were important for building a successful practice.
      Formal teaching methods were clearly associated with improved perception of
      proficiency, and those with higher perception of proficiency expected to perform
      more laparoscopic procedures after graduation. Residents lacked perceived
      competency in most advanced laparoscopic procedures. CONCLUSION: Residents seem
      to benefit significantly from a formal curriculum in minimally invasive surgery,
      but they do not feel competent performing some advanced procedures on graduation.
      In our opinion, more emphasis should be placed on training in laparoscopic
      surgery in United States obstetrics and gynecology programs.

PMID- 11960042
TI  - Short-term administration of tibolone plus GnRH analog before laparoscopic
      myomectomy.
AB  - STUDY OBJECTIVE: To evaluate whether tibolone modifies the effectiveness of
      gonadotropin-releasing hormone (GnRH) analog administered before laparoscopic
      myomectomy. DESIGN: Prospective, randomized, open, placebo-controlled clinical
      trial (Canadian Task Force classification I). SETTING: University-affiliated
      hospital. PATIENTS: Sixty-six women with symptomatic leiomyomas. INTERVENTIONS:
      Patients received 2 months of treatment with GnRH analog and iron plus tibolone
      (group A) or placebo (group B); group C received only iron. Laparoscopic
      myomectomy was performed after medical treatment. MEASUREMENTS AND MAIN RESULTS:
      Uterine volume, number and volume of leiomyomas, echogenicity and volume of the
      largest leiomyomas, hematologic values, and myoma-related symptoms were evaluated
      at baseline, 1 week before, and 1 week after surgery. We observed significant (p
      <0.05) reductions in uterine and leiomyomata volume, myoma-related symptoms, and
      improvement in hematologic values before surgery in groups A and B, without
      significant difference between groups compared with baseline values and group C.
      Operating time and blood loss were significantly (p <0.05) lower in groups A and
      B, without significant difference compared with group C. After surgery,
      significant numbers of women in group C had worsening of hematologic values (p
      <0.05). CONCLUSION: Adding tibolone to the GnRH analog regimen before
      laparoscopic myomectomy does not modify the effectiveness of GnRH analog
      administered alone.

PMID- 11960043
TI  - Perioperative complication rates of primary and repeat hysteroscopic endometrial
      ablations.
AB  - STUDY OBJECTIVE: To determine perioperative complication rates at primary and
      repeat endometrial ablations. DESIGN: Prospective cohort study (Canadian Task
      Force classification II-2). SETTING: Tertiary care teaching hospital. PATIENTS:
      Seventy-five women who underwent a repeat ablation and 800 who had a primary
      ablation by the same surgeon (GAV) between 1990 and 2000 for a diagnosis of
      menorrhagia and/or dysmenorrhea. INTERVENTIONS: Hysteroscopic ablation involving
      coagulation or resection of endometrium, and second ablation after failure of the
      first. MEASUREMENTS AND MAIN RESULTS: Serious perioperative complications were
      uterine perforation, hemorrhage, excess fluid absorption, and genital tract
      burns. They occurred in 9.3% of repeat ablations compared with 2.05% of primary
      ablations (p = 0.006). CONCLUSION: Repeat endometrial ablation has a
      significantly higher rate of perioperative complications than primary ablation.

PMID- 11960044
TI  - Two techniques of laparoscopic retropubic urethropexy.
AB  - STUDY OBJECTIVE: To compare two techniques of transperitoneal laparoscopic
      urethropexy. DESIGN: Prospective, randomized, open trial (Canadian Task Force
      classification I). SETTING: University-affiliated department of gynecology and
      obstetrics. PATIENTS: Sixty women with genuine stress incontinence.
      INTERVENTIONS: Transperitoneal laparoscopic retropubic urethropexy using
      nonabsorbable sutures (group A) and polypropylene mesh fixed with tacks or
      staples (group B). MEASUREMENTS AND MAIN RESULTS: Failure was assessed
      subjectively and objectively. Subjective evaluation was performed asking patients
      if they had urine loss and having them describe symptomatology on a visual analog
      scale before surgery and at each follow-up visit. Objective evaluation was by
      clinical examination and/or multichannel urodynamic studies. No significant
      differences in intraoperative and postoperative complications were observed
      between groups. The subjective failure rate was not significantly different
      between groups 3, 6, and 12 months after surgery. At 3 and 6 months the objective
      failure rate was not significantly different; however, at 12 months it was
      significantly lower in group A than in group B. CONCLUSION: Transperitoneal
      laparoscopic retropubic urethropexy is more effective with sutures than with
      mesh.

PMID- 11960045
TI  - Intrauterine adhesions after conservative and surgical management of spontaneous
      abortion.
AB  - STUDY OBJECTIVE: To determine the frequency of intrauterine adhesions (IUA) after
      conservative management, medical evacuation, and surgical evacuation for
      spontaneous abortion. DESIGN: Prospective follow-up study (Canadian Task Force
      classification II-2). SETTING: Gynecology unit in a teaching hospital. PATIENTS:
      Eighty-two women who had been treated with conservative management, medical
      evacuation, or surgical evacuation of retained products of conception after
      spontaneous abortions in a randomized, controlled trial. MEASUREMENTS AND MAIN
      RESULTS: Hysteroscopic diagnosis of IUA 6 months after initial treatment was the
      primary outcome measure. No cases of IUA were found in patients managed
      conservatively or by medical evacuation, whereas two cases (7.7%) of filmy IUA
      were detected in those managed by surgical evacuation. There was no statistical
      significant difference in the rate of self-reported reduced menstrual flow 6
      months after initial treatment by any method. CONCLUSION: The prevalence of IUA
      was low after each modality of treatment for spontaneous abortion. Conservative
      management and medical evacuation are both acceptable alternatives to standard
      surgical evacuation.

PMID- 11960046
TI  - Long-term histopathologic and morphologic changes after thermal endometrial
      ablation.
AB  - STUDY OBJECTIVE: To outline long-term histologic features of endometrial
      ablation. DESIGN: Prospective longitudinal study (Canadian Task Force
      classification II-3). SETTING: Tertiary-care teaching hospital. PATIENTS: Twenty
      six patients. INTERVENTION: Thermal ablation followed by second-look office
      hysteroscopy with endometrial biopsy. MEASUREMENTS AND MAIN RESULTS: Mean follow
      up time to second-look hysteroscopy after ablation was 33.4 +/- 2,1 months.
      Complete atrophy, partial adhesions or obliteration of the cavity, and fibrosis
      were observed at second-look hysteroscopy. Whereas all random biopsies were
      normal before ablation, biopsies after ablation revealed diminished endometrial
      glands with necrosis and scarring. The number of endometrial glands was not
      correlated with amount of bleeding or menstrual pattern. No premalignant or
      malignant lesions were found after ablation. CONCLUSION: Although efficacy of
      endometrial ablation is related to initial thermal destruction and correlated
      with postablation hysteroscopic and histologic findings, endometrial regrowth is
      an expected development, not a failure of ablation.

PMID- 11960047
TI  - Laparoscopic uterine artery occlusion for symptomatic leiomyomas.
AB  - STUDY OBJECTIVE: To describe a laparoscopic technique that safely occludes both
      uterine arteries, overcoming an altered surgical field resulting from scarring
      and/or uterine leiomyomatous growth. DESIGN: Prospective analysis (Canadian Task
      Force classification II-2). SETTING: Nonprofit community hospital. PATIENTS:
      Eight women with leiomyomas with abnormal uterine bleeding, pelvic pain or
      pressure, and/or anemia. INTERVENTION: Bilateral laparoscopic retroperitoneal
      uterine artery occlusion. MEASUREMENTS AND MAIN RESULTS: Occlusion at the initial
      track of the uterine artery was performed by laparoscopic coated ligature in six
      patients. In two obese patients with deep retroperitoneal space, vascular clips
      were placed endoscopically using the same dissecting technique. All patients were
      discharged within 20 hours after the procedure. All five women with abnormal
      bleeding reported satisfactory decrease; none reported amenorrhea. Of eight with
      preoperative pain or pressure, seven reported complete disappearance and one
      significant relief. All three patients with anemia had normal red cell counts
      after 1 month. CONCLUSION: Laparoscopic uterine artery occlusion using a lateral
      retroperitoneal technique is safe and effective in women with pelvic scarring and
      altered pelvic anatomy.

PMID- 11960048
TI  - Left upper quadrant approach in gynecologic laparoscopic surgery using reusable
      instruments.
AB  - STUDY OBJECTIVE: To determine the usefulness of the left upper quadrant approach
      in gynecologic laparoscopic surgery. DESIGN: Retrospective study (Canadian Task
      Force classification II-2). SETTING: University referral center. PATIENTS: Twenty
      four women with longitudinal scars from previous laparotomy through or close to
      the umbilicus. INTERVENTION: Left upper quadrant was chosen as the site of
      primary entry of the reusable Veress needle (ninth or tenth left intercostal
      space) and reusable primary cannula (left upper quadrant just below the left
      subcostal margin). MEASUREMENTS AND MAIN RESULTS: Intraabdominal adhesions
      between old longitudinal scars and underlying bowel or omentum were present in 14
      patients. Adhesions involving omentum only were present in 10 patients, bowel
      only in 2, and both omentum and bowel in 2. The only intraoperative complication
      was emphysema in one woman. All operative procedures were completed
      laparoscopically. CONCLUSION: The left upper quadrant approach is a safe entry
      point for reusable instruments at laparoscopic surgery in patients with midline
      incisions close to the umbilicus.

PMID- 11960049
TI  - Neovagina construction by combined laparoscopic-perineal sigmoid colpoplasty in a
      patient with Rokitansky syndrome.
AB  - We created a neovagina by sigmoid colpoplasty using a combined laparoscopic
      perineal approach in a 19-year-old woman with Rokitansky syndrome. Operating time
      was 4 hours and 45 minutes. No perioperative or postoperative complications
      occurred. Hemoglobin level fell by 1 g/dl. Total doses of morphine, nonsteroidal
      antiinflammatory drugs (NSAIDs), and paracetamol were 20 mg, 350 mg, and 28 g,
      respectively. Hospital stay was 7 days. The length of the neovagina was 12 cm. By
      comparison, in the three reported cases of laparotomic-perineal sigmoid
      vaginoplasty, mean operating time was 5 hours and 40 minutes; 24-hour fall in
      hemoglobin was 3.2 g/dl (range 2.1-4.3 g/dl); mean doses of morphine, NSAIDs, and
      paracetamol were 42.6 mg, 300 mg, and 40 g, respectively; mean hospital stay was
      11.3 days; and length of neovaginas was 10, 12, and 12 cm. Although sigmoid
      colpoplasty is a reliable and reproducible technique, it requires experience in
      laparoscopic colonic surgery. The combined laparoscopic-perineal approach is
      associated with less analgesic requirement, shorter hospital stay, and similar
      anatomic results compared with the laparotomic-perineal approach.

PMID- 11960050
TI  - Hysteroscopic treatment of intrauterine lesions in premenopausal and
      postmenopausal women.
AB  - STUDY OBJECTIVE: To compare the safety and efficacy of hysteroscopic surgery in
      the management of intrauterine lesions in premenopausal and postmenopausal women
      and, in particular, to investigate whether glycine absorption is different
      between these populations. DESIGN: Comparative study (Canadian Task Force
      classification II-2). SETTING: Tertiary care university hospital. PATIENTS:
      Thirty postmenopausal and 78 premenopausal women with intrauterine polyps or
      myomas. INTERVENTION: Hysteroscopic myomectomy or polypectomy. MEASUREMENTS AND
      MAIN RESULTS: One hundred eight procedures were completed successfully by
      hysteroscopy; in two cases myomectomy was completed in a second operation for a
      deeply embedded myoma. No major complications occurred in either group. Median
      operating time, mean glycine absorption, and median postoperative hospital stay
      were not significantly different between groups. During mean follow-up of 15
      months (range 1-39 mo), four women underwent hysterectomy (1 for endometrial
      cancer, 1 for complex hyperplasia with atypia, 2 for pelvic pain and
      menorrhagia). CONCLUSION: Hysteroscopic surgery is an effective and safe
      therapeutic option for intrauterine lesions regardless of a woman's menopausal
      status.

PMID- 11960052
TI  - Ischemic uterine rupture and hysterectomy 3 months after uterine artery
      embolization.
AB  - The exact frequency and extent of complications after uterine artery embolization
      (UAE) have yet to be documented in the literature. Ischemic necrosis and rupture
      of the uterus is a theoretical concern of this procedure. Rupture of the uterus
      from any cause is a very serious gynecologic complication requiring immediate
      surgical intervention to prevent death. Ischemic necrosis and rupture of the
      uterus can occur months after UAE. In our patient they occurred 3 months after
      UAE for treatment of symptomatic uterine myomas, and required hysterectomy. To
      our knowledge, this is the first report of ischemic uterine rupture after UAE in
      the United States.

PMID- 11960051
TI  - A simple, inexpensive method of specimen removal at laparoscopy.
AB  - After completing operative laparoscopy, it is often necessary to enlarge a 5-mm
      port to 10 or 12 mm for tissue removal. This may increase the risk of vessel
      injury and herniation, and has obvious cosmetic drawbacks. A simple, cost
      effective technique for tissue removal does not require enlarging the 5-mm port.
      A long, firm thread is sutured to a sterile plastic bag. When tissue removal is
      required, the optic telescope is removed and the bag is blindly introduced
      through the available optical 11- or 12-mm cannula. The telescope is
      reintroduced, keeping the end of the thread outside the cannula sleeve. The
      specimen is placed in the bag and the bag is removed by pulling the suture
      through the optical cannula after removing the telescope. This technique was
      performed successfully in over 300 patients, with no difficulty or complication
      either during or after surgery. The device is inexpensive and takes 2 minutes to
      assemble.

PMID- 11960053
TI  - Laparoscopic treatment of primary ovarian pregnancy.
AB  - Ovarian pregnancy is an uncommon type of ectopic pregnancy. A 35-year-old,
      gravida 3, para 3 woman was admitted because of a vaginal bleeding of 17 days'
      duration after amenorrhea for 10 weeks. She had right lower quadrant pain. Serum
      beta-human chorionic gonadotropin concentration was 1530 mIU/ml. Transabdominal
      ultrasonography showed a normal-size uterus, empty uterine cavity, solid cystic
      mass 43 x 39 mm on the right adnexa, and no free fluid in the pouch of Douglas.
      Diagnostic operative laparoscopy under general anesthesia was performed for
      suspected ectopic pregnancy. Right oophorectomy was done because of minimal
      intact ovary tissue. It was later histopathologically confirmed as primary
      ovarian pregnancy. The woman experienced no postoperative complications.

PMID- 11960054
TI  - Comparison of sonohysterography and hysteroscopy: lessons learned and avoiding
      pitfalls.
AB  - We compared ultrasound images of the uterine cavity obtained by sonohysterography
      (SHG) with those of hysteroscopy in an attempt to avoid inaccurate
      interpretations. Women referred for abnormal bleeding or infertility underwent
      SHG before treatment. Those with an abnormal study underwent hysteroscopy for
      confirmation and treatment. Abnormal SHG studies are frequent, with false
      positive images including blood clots, mucus plugs, and shearing of normal
      endometrium relatively common. Uterine pathology generally seen on SHG, including
      anomalies, polyps, and myomas, is consistent with that seen at hysteroscopy.
      Performing intraoperative SHG concomitantly with hysteroscopy adds value due to
      SHG's three-dimensional images to confirm depth of pathology and false negative
      hysteroscopy findings.

PMID- 11960055
TI  - Biochemical changes after laparoscopy and bladder injury.

PMID- 11960056
TI  - Toupet or not Toupet, that is the question.

PMID- 11960057
TI  - Associated primary tumors in patients with gastric cancer.

PMID- 11960059
TI  - Training and certifying gastroenterologists as physician nutrition specialists.
AB  - Because nutrition is an integral aspect of the science and practice of
      gastroenterology, all gastroenterology fellows should receive training in core
      aspects of nutrition (level 1 training). Some gastroenterologists also wish to
      train more extensively in nutrition (level 2) and become physician nutrition
      specialists. The Intersociety Professional Nutrition Education Consortium,
      composed of representatives from eight national societies with significant
      nutrition interests, including the American Gastroenterological Association, and
      three credentialing bodies, has developed a paradigm and training requirements
      for physician-nutrition specialists that recognizes their varied backgrounds and
      areas of interest. Opportunities exist for gastroenterology fellows to obtain
      physician nutrition specialist training within their gastroenterology fellowships
      and to be eligible to take the Certification Examination for Physician Nutrition
      Specialists offered by the new American Board of Physician Nutrition
      Specialists.* This article reviews the development of consensus on subspecialty
      training for physicians in nutrition; it also encourages directors of
      gastroenterology fellowships to develop training opportunities and
      gastroenterology fellows to consider identifying nutrition as an area of emphasis
      for their careers.

PMID- 11960060
TI  - Characterization of long-term outcomes after Toupet fundoplication: symptoms,
      medication use, and health status.
AB  - GOALS AND BACKGROUND: Fundoplication is increasingly used for the treatment of
      gastroesophageal reflux disease (GERD). Few studies have tracked patient outcomes
      of the Toupet method for more than 1 year. Further clinical, physiologic, and
      patient-based outcome measures have not been well characterized for this method.
      The current study conducts a long-term, comprehensive outcome evaluation in
      patients receiving Toupet fundoplication. STUDY: Fifty-five patients who had
      previously undergone fundoplication were examined. In a subset of 24 patients,
      esophagogastroduodenoscopy was used to assess the severity of reflux esophagitis.
      Manometry and ambulatory pH monitoring also were performed. RESULTS: Patients
      were studied 2.9 (+/- 0.7) years after surgery. Sixty-seven percent of the sample
      reported heartburn, 51% reported postoperative bloating, 33% reported
      regurgitation, and 20% reported dysphagia. Thirty-three percent reported the use
      of prescription medications for GERD-related symptoms. Health status was
      diminished relative to population norms. Degree of GERD severity was associated
      with symptom reports and medication use. CONCLUSIONS: Although fundoplication is
      thought to be a curative procedure, the current findings suggest that many
      patients take symptomatic therapies and report symptoms and diminished health
      status up to 2 years after the procedure. These outcomes are associated with
      physiologic findings. Thus, these findings suggest that symptom-free status and
      absence of medication use cannot be assumed for all patients after Toupet
      fundoplication.

PMID- 11960061
TI  - Sociodemographics, general health, and psychologic health in uninvestigated
      dyspepsia: a comparison of public and private patients.
AB  - GOALS: To compare the dyspepsia severity, general health, and psychologic health
      of patients with uninvestigated dyspepsia presenting in private and public
      settings. STUDY: Patients in this cross-sectional study were recruited from the
      Houston Veterans Administration (VA) General Medicine Outpatient Clinic and from
      the nearby private practice of a family physician. To be included, patients had
      to be at least 18 years of age and had to report a history of dyspepsia
      (epigastric discomfort) without alarm of at least 1 week's duration. Clinical
      information was obtained. Dyspepsia severity was measured using dyspepsia-related
      health scales, general health was measured using the Short Form 36, and
      psychologic health was measured using six scales. RESULTS: The authors enrolled
      159 patients (59 VA). There were no differences in VA and private patients in
      most of the clinical characteristics related to dyspepsia. Compared with the
      private patients, the VA patients had worse scores on all Short Form 36
      subscales, had lower expectations for treatment outcome, were more depressed, and
      had less optimism about life. CONCLUSIONS: Burden of illness and psychologic
      factors such as patient expectations are known to have important effects on
      patient outcomes. Striking differences in these factors exist in patients with
      uninvestigated dyspepsia seen in private and public settings. In the future,
      these factors must be taken into account both in conducting studies in dyspepsia
      and in interpreting the results for different practice settings.

PMID- 11960062
TI  - Atypical and aggressive upper gastrointestinal ulceration associated with aspirin
      abuse.
AB  - BACKGROUND: Unusual resistance to treatment in 5% to 7% of 1,845 peptic ulcers
      examined under endoscopy from 1987 to 1996 prompted a search for unusual causes.
      Although some ulcers were caused by Zollinger-Ellison syndrome (ZES), an atypical
      clinical course in other patients, especially with those with multiple ulcers,
      suggested abuse of aspirin. STUDY: Patients who did not have ZES were questioned
      closely regarding aspirin use and were tested for serum salicylate to detect
      surreptitious abuse. RESULTS: The authors identified 37 patients with aspirin
      related ulcers but otherwise intact upper gastrointestinal tracts. There were 12
      men and 25 women aged 18 to 73 years; 18 admitted to current aspirin abuse (>1
      g/d), but 19 denied it despite objective evidence from elevated serum salicylate
      (8.4 +/- 1.2 mg/dL). The clinical presentation was atypical, with only 10
      patients having single ulcers, whereas 27 had 83 multiple or multiorgan ulcers.
      Overall, there were 32 duodenal, 57 gastric, and 4 esophageal ulcers. Omeprazole
      healed 64% of ulcers, but despite follow-up maintenance with H2 receptor
      antagonists, all ulcers recurred rapidly, often in a new location. Thirty of 37
      patients had serious complications: 18 bled; 9 had pyloric and 2, duodenal
      stenosis; 2, esophageal strictures; and 2, perforation. Six patients who stopped
      using aspirin healed easily. The 80% who did not stop on advice after diagnosis
      were considered abusers. CONCLUSION: Patients with aspirin abuse have atypical,
      often multiple, intractable ulcers with many complications. These ulcers differ
      from conventional Helicobacter pylori peptic ulcers and also from those found in
      patients with ZES. Unless aspirin use is stopped, these ulcers remain incurable
      and dangerous.

PMID- 11960063
TI  - Endoscopic evidence of mucosal injury in patients taking ticlopidine compared
      with patients taking aspirin/nonsteroidal antiinflammatory drugs and controls.
AB  - BACKGROUND: Ticlopidine is a novel antiplatelet agent used alone or in
      combination with aspirin and anticoagulants in the treatment and prevention of
      various vascular diseases. Gastrointestinal side effects, including bleeding,
      have been reported with use of ticlopidine in most of the vascular prevention
      trials. We studied the endoscopic evidence of mucosal damage in patients taking
      ticlopidine compared with patients taking aspirin/nonsteroidal antiinflammatory
      drugs (NSAIDs) and matched controls. STUDY: We performed a longitudinal review of
      gastrointestinal endoscopy, pharmacy databases, and medical records of patients
      referred to our service over a period of 6 months for endoscopic evaluation of
      upper gastrointestinal bleeding, unexplained anemia, or abdominal pain. Data were
      collected and analyzed for 55 patients taking ticlopidine, 77 age- and gender
      matched patients taking aspirin or NSAIDs, and 560 age- and gender-matched
      control patients not taking any of these medications. RESULTS: The overall
      prevalence of ulcers was marginally higher in the aspirin/NSAID group than in the
      ticlopidine group (35% vs. 29%) and was significantly higher among patients
      taking aspirin, NSAIDs, or ticlopidine than among controls (15%). Gastritis was
      also noted more frequently in the aspirin/NSAID and ticlopidine groups than in
      the control group. Endoscopic evidence of esophagitis was significantly more
      frequent in the control group than in the aspirin/NSAID and ticlopidine groups.
      There was no significant difference across groups in the prevalence of ulcers,
      gastritis, or esophagitis. CONCLUSIONS: Patients taking ticlopidine are more
      likely to have endoscopic evidence of mucosal damage than matched control
      patients and are nearly as likely to have such damage as endoscopically evaluated
      patients taking aspirin or NSAIDs. However, these findings must be confirmed
      using prospective cohort data for patients in primary care settings, to avoid
      referral bias.

PMID- 11960064
TI  - Associated primary tumors in patients with gastric cancer.
AB  - GOAL: To determine the prevalence of associated primary tumors in patients with
      gastric cancer. STUDY: Retrospective study of 2,668 patients with gastric cancer
      observed at our department between July 1974 and December 1999. Associated tumors
      were diagnosed using Warren and Gates criteria, and included tumors that were not
      considered to be a metastasis, invasion, or recurrence of gastric cancer.
      RESULTS: Of all, 3.4% (n = 78) had primary tumors other than gastric cancer, 27%
      of which were synchronous (n = 21) and 73%, metachronous (n = 57). The mean
      follow-up time was 4 years (range, 1-13 years), and the male-to-female ratio was
      1:1. The median age at diagnosis of gastric cancer was 67 years (range, 37-84
      years), 69 years for patients with synchronous tumors versus 60 years for those
      with metachronous (p = 0.050). For at least half the patients the median time
      interval to metachronous cancer was 3 years (range, 1-22 years). Seventy-eight
      percent (n = 61) had two cancers; most were colonic (19%), uterine and ovarian
      (16%), and breast tumors (13%). Seventeen percent (n = 13) had three tumors:
      colon (46%), breast (23%), and skin (23%). Four percent (n = 3) had four tumors.
      One case with seven tumors was also observed [colon, breast (two tumors), uterus,
      skin, and stomach (two tumors)]. No statistically significant differences were
      found between synchronous and metachronous with regard to sex, gastric cancer
      location, and staging (TNM). Sixty-three percent (n = 49) died while under
      observation. CONCLUSIONS: We found associated tumors in 3.4% of patients with
      gastric cancer. The most frequent associated tumors were breast and colon cancer.
      Surveillance for these tumors would be appropriate, at least in first years,
      after diagnosis of gastric cancer.

PMID- 11960065
TI  - Prolonged use of proton pump inhibitors, CagA status, and the outcome of
      Helicobacter pylori gastritis.
AB  - GOALS AND BACKGROUND: To assess whether prolonged use of proton pump inhibitors
      (PPIs) in patients infected with Helicobacter pylori has adverse effects on
      gastritis. STUDY: We studied 34 H. pylori-positive individuals with reflux
      esophagitis, Barrett esophagus, or nonulcer dyspepsia. Half of them were on
      maintenance treatment with PPIs (mean, 8 years) and half were not.H. pylori and
      CagA status were tested serologically. Gastric biopsies were classified
      histopathologically by the updated Sydney classification. RESULTS: Proton pump
      inhibitors in H. pylori gastritis are associated with significantly less antral
      inflammation and lower H. pylori density, regardless of CagA status. There was a
      tendency toward more antral atrophy in patients with the CagA strain who were
      undergoing maintenance treatment with PPIs (p = 0.08), but there was an opposite
      tendency in CagA-negative individuals (p = 0.08). Intestinal metaplasia was seen
      more frequently in CagA-positive, treated individuals (p = 0.028). CONCLUSIONS:
      These findings support the hypothesis that CagA status is important in the
      progression to atrophy and that maintenance treatment with PPIs accelerate this
      progression, while reducing inflammatory infiltration.

PMID- 11960066
TI  - The incidence of Helicobacter pylori infection is not increased among obese young
      individuals in Greece.
AB  - GOALS: To identify possible risk factors affecting the acquisition of
      Helicobacter pylori (Hp) infection and to investigate whether the incidence of
      infection is higher among obese and overweight verus normal-weight young adults
      in Greece. STUDY: Serum was obtained from 224 young male Navy recruits (mean age,
      22.84 years) during their induction into the Hellenic Navy. An enzyme-linked
      immunosorbent assay to detect Hp-specific IgG serum antibodies, as well as
      gastroscopy with biopsy, were used to identify the infected individuals. A
      structured questionnaire was filled out for each subject regarding environmental
      conditions, socioeconomic conditions, dietary habits, and data related to their
      personal and family health history. RESULTS: H. pylori positivity rate was
      27.23%. Univariate analysis recognized that the number of siblings in the same
      bedroom was significantly higher among Hp-positive than Hp-negative individuals.
      Logistic regression analysis showed that sharing the same bedroom with more than
      one sibling during childhood and consumption of fast food are independent
      predictors of Hp acquisition. The presence of obesity (body mass index > or =25
      kg/m2) remained unrelated to the Hp status of the individuals. CONCLUSIONS: These
      data suggest that the risk of Hp infection does not increase in overweight young
      persons. Sharing the same bedroom with more than one sibling during childhood is
      an important determinant in acquiring Hp infection. Increased fast food
      consumption could be an important source of the infection outside of the home.

PMID- 11960067
TI  - One-week quadruple therapy is an effective salvage regimen for Helicobacter
      pylori infection in patients after failure of standard triple therapy.
AB  - Standard triple therapy remains an important option for eradicating Helicobacter
      pylori (Hp) in developing countries because of its relatively low cost. However,
      salvage therapies after failure of this regimen remain undefined. The authors
      therefore investigate the efficacy of 1-week quadruple therapy as a second-line
      treatment of Hp infection after failure of standard triple therapy. Seventy-eight
      patients who failed Hp eradication using a 2-week bismuth-based triple therapy
      were enrolled and received a course of 1-week quadruple therapy (lansoprazole, 30
      mg twice daily; bismuth subcitrate, 120 mg four times daily; clarithromycin, 500
      mg twice daily; and amoxicillin, 1,000 mg twice daily) as a salvage regimen. The
      Hp status was reassessed 7 weeks after cessation of therapy. Among the 78
      patients, Hp eradication was achieved in 65 (83%, 95% confidence interval = 75
      91%) by intention-to-treat analysis. Only five (6%) patients had side effects,
      and all (100%) showed good drug compliance. Multivariate analysis disclosed that
      coffee drinking was an independent factor for treatment failure (odds ratio =
      5.3, 95% confidence interval = 1.2-23.6, p = 0.028). The authors therefore
      conclude that their 1-week quadruple therapy is an effective salvage regimen for
      Hp infection after failure of standard triple therapy in the population examined.
      The benefits of this regimen include the high eradication rate, the short
      duration of treatment, fewer side effects, and good drug compliance. Coffee
      consumption possibly is an important factor in failure of the rescue regimen. The
      mechanisms underlying the association between coffee drinking and eradication
      failure require further research.

PMID- 11960068
TI  - Eosinophilic gastroenteritis and gluten-sensitive enteropathy in the same
      patient.
AB  - We report the clinical and laboratory features of a 19-year-old man with findings
      of both eosinophilic gastroenteritis and gluten-sensitive enteropathy. Before the
      onset of clinical symptoms, the patient had received a series of hepatitis B
      vaccinations but had not developed a measurable antibody response or any allergic
      reaction. Radioallergosorbent test results were positive to several foods, and
      the total serum immunoglobulin E (IgE) level was elevated. Adherence to a gluten
      free diet caused a normalization in the endomysial antibody titer; however, the
      total serum IgE level continued to increase, and the total eosinophil count
      remained elevated. Symptoms of recurrent vomiting and abdominal pain necessitated
      prednisone burst therapy. The simultaneous occurrence of eosinophilic
      gastroenteritis and gluten-sensitive enteropathy is rare; therapy should be
      directed to each disorder individually.

PMID- 11960069
TI  - Isolated superior mesenteric artery thrombosis: a rare cause for recurrent
      abdominal pain in a child.
AB  - A 4-year-old boy was evaluated for recurrent abdominal pain and failure to thrive
      over a 1-year period in a pediatric subspecialty clinic. Results of the extensive
      workup mostly were unremarkable. Eventually, imaging studies of the abdominal
      aorta revealed an isolated thrombosis of the superior mesenteric artery trunk and
      compensatory hypertrophy of the inferior mesenteric artery. He had been having
      abdominal angina symptoms and fear of eating. A detailed family history suggested
      a possible hypercoagulable state. However, an extensive hematologic evaluation
      did not reveal a recognizable defect that could produce thrombotic events. He was
      treated by arterial graft bypass surgery and started on conventional
      anticoagulants. Several months later, he developed repeat, near-total thrombosis
      of the graft with recurrence of his symptoms. After balloon dilation of the graft
      and starting him on appropriate anticoagulant maintenance regimen, he had good
      symptom relief, and the graft remained patent. This presentation was unusually
      prolonged for the type of vascular problem identified. The possibility of
      vascular problems in children, therefore, should be considered. Unidentified
      cause of hereditary clotting tendency is another challenging aspect of this case.

PMID- 11960070
TI  - Cheilitis granulomatosa and optic neuropathy as rare extraintestinal
      manifestations of Crohn's disease.
AB  - Crohn's disease can be accompanied by extraintestinal manifestations. The authors
      report on a 39-year-old patient who presented with cheilitis granulomatosa as the
      first manifestation of Crohn's disease. Four years later, intestinal Crohn's
      disease was diagnosed. One year afterward, acute loss of visual acuity from optic
      neuropathy developed as another rare extraintestinal manifestation of Crohn's
      disease.

PMID- 11960071
TI  - The role of endoscopic retrograde cholangiopancreatography in acute and chronic
      pancreatitis.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) plays a pivotal role in the
      management of patients with acute and chronic pancreatitis. Whereas endoscopic
      observation during ERCP permits recognition of abnormalities involving the major
      and minor duodenal papillae such as papillary tumors or choledochocele,
      radiographic evaluation enables the detection of structural abnormalities of
      pancreaticobiliary ducts like strictures or calculi. Sphincter of Oddi manometry,
      a technical advance of ERCP, is essential for the diagnosis of sphincter of Oddi
      dysfunction, which may present clinically as recurrent pancreatitis. Because
      structural alterations of the pancreatic duct forms the hallmark of chronic
      pancreatitis, ERCP is highly sensitive and specific in diagnosing chronic
      pancreatitis. Apart from its diagnostic role, ERCP offers a variety of
      possibilities for therapeutic interventions in selected problems associated with
      pancreatitis. Endoscopic papillectomy and mucosal resection for tumors of the
      papilla, unroofing of a choledochocele, and sphincterotomy for sphincter ablation
      in sphincter of Oddi dysfunction are some of the therapeutic interventions
      possible during ERCP. Pancreatic ductal hypertension, which is considered to be
      the major pathophysiologic mechanism for disabling abdominal pain in chronic
      pancreatitis, also can be managed by ERCP-directed treatments. Pancreatic
      sphincterotomy, dilation of strictures, lithotripsy, extraction of calculi, and
      deployment of endoprosthesis constitute the commonly used therapeutic techniques
      in this situation. Besides offering a noninvasive alternative, these treatments
      are associated with a favorable clinical outcome comparable with that of
      operative treatments. Nevertheless, complications such as acute pancreatitis,
      bleeding, perforation, or sepsis may occur in 5% to 10% of patients undergoing
      these procedures. Therefore, careful selection of patients, appropriate
      preoperative care, and a team approach, including surgeon, interventional
      radiologist, and endoscopist, are important.

PMID- 11960072
TI  - Survival and prognostic indicators in patients with hepatitis B virus-related
      cirrhosis after onset of hepatic decompensation.
AB  - GOALS: To determine the 2-year survival and prognostic indicators of hepatitis B
      virus-related cirrhosis after the onset of hepatic decompensation. BACKGROUND:
      Chronic hepatitis B (CHB) patients with cirrhosis and resultant hepatic
      decompensation have reduced survival. However, the natural history of these
      patients has not been well characterized in previous studies. Better
      understanding of survival and prognostic indicators is essential in management of
      these patients, especially in determining who should be candidates for orthotopic
      liver transplantation. STUDY: This is a retrospective longitudinal study of 96
      patients with CHB-related cirrhosis after the onset of hepatic decompensation.
      The overall survival was ascertained, and clinical and laboratory variables were
      analyzed. Significant prognostic indicators for survival at 2 years were
      determined using univariate and multivariate analyses with Cox regression model.
      RESULTS: The overall survival was 80% at 2 years after onset of decompensation.
      With univariate and multivariate analyses, hepatic encephalopathy and
      hypoalbuminemia less than 2.8 g/dL were significant prognostic indicators of poor
      survival probability. The hazard ratios were 5.22 (95% confidence interval, 1.67
      16.3) and 8.57 (95% confidence interval, 1.94-37.8), respectively. Patients with
      hypoalbuminemia less than 2.8 g/dL had a 2-year survival of only 62%.
      CONCLUSIONS: Our study showed that of CHB patients who developed the first
      episode of hepatic decompensation, those with hepatic encephalopathy or
      significant hypoalbuminemia or both have worse prognoses. They should be
      considered potential candidates for liver transplantation.

PMID- 11960073
TI  - Duplex Doppler ultrasound of the hepatic artery in patients with acute alcoholic
      hepatitis.
AB  - BACKGROUND: Acute alcoholic hepatitis (AAH) is a clinical diagnosis associated
      with increased hepatic artery diameter and flow. Duplex Doppler ultrasound (DDU)
      has been shown to accurately measure arterial flow in both liver and kidney
      transplant patients. The authors conducted a blinded, controlled study to
      evaluate the accuracy of measuring hepatic artery parameters with DDU in
      diagnosing AAH. STUDY: Duplex Doppler ultrasound was performed by an
      investigator, blinded to group makeup, on 22 consecutive hospital inpatients with
      the clinical diagnosis of AAH. The diagnosis of AAH was based on specific
      criteria, including the following: recent alcohol abuse, hyperbilirubinemia,
      prolonged prothrombin time, leukocytosis, hepatomegaly, hepatic bruit, and marked
      redistribution of isotope on 99mTc-sulfur colloid liver-spleen scan. Controls
      were 12 cirrhotic patients without AAH and 17 healthy volunteers. Duplex Doppler
      ultrasound measurements were obtained most consistently from the proximal right
      hepatic artery. Measured parameters included the following: peak systolic
      velocity (PSV); resistive index = (PSV - end diastolic velocity [EDV])/PSV;
      pulsatility index = (PSV - EDV)/mean velocity; and hepatic artery diameter.
      RESULTS: The mean hepatic artery diameter was significantly larger in patients
      with AAH (3.55 +/- 0.72 mm) than in patients with cirrhosis (2.75 +/- 0.69 mm; p
      = 0.003) and healthy controls (2.68 +/- 0.69 mm; p = 0.001). The mean PSV was
      significantly higher in patients with AAH (187 +/- 52 cm/s) compared with
      cirrhotic (67 +/- 51 cm/s) and healthy (66 +/- 51 cm/s) controls (p = 0.0001).
      The mean resistive index was lower in AAH patients (0.60 +/- 0.11) compared with
      cirrhotic (0.69 +/- 0.10; p value was not significant) and healthy controls (0.72
      +/- 0.11; p = 0.004). The mean pulsatility index was lower in AAH patients (1.04
      +/- 0.47) compared with cirrhotic (1.36 +/- 0.45; p value was not significant)
      and healthy controls (1.53 +/- 0.45; p = 0.01). CONCLUSIONS: In the appropriate
      clinical setting, an elevated hepatic artery diameter or PSV measurement is
      suggestive of AAH. Duplex Doppler ultrasound offers a noninvasive test to assist
      in the diagnosis of AAH.

PMID- 11960074
TI  - Helicobacter pylori, gastric juice, and arterial ammonia levels in patients with
      cirrhosis.
AB  - Helicobacter pylori urease activity is a potential source of ammonia in the
      stomach of patients with cirrhosis. However, the possible role of H. pylori in
      the pathogenesis of hepatic encephalopathy deserves further investigations. The
      current study evaluates the relationship among H. pylori infection, gastric juice
      ammonia concentrations, and arterial ammonia levels in patients with cirrhosis.
      Overall, 14 patients with cirrhosis with overt hepatic encephalopathy, 19 with
      subclinical hepatic encephalopathy, and 13 without encephalopathy were enrolled.
      All patients underwent upper endoscopy, and gastric biopsy specimens were taken
      for H. pylori assessment (rapid urease test, histology, and culture). A gastric
      juice sample and an arterial blood sample were obtained for ammonia level
      assessment. Patients with overt encephalopathy had both higher arterial ammonia
      levels and a more severe hepatic impairment than the remaining patients, whereas
      gastric juice ammonia concentrations did not differ among the three groups. H.
      pylori prevalence was similar among groups. Patients with H. pylori infection had
      significantly higher gastric juice ammonia concentrations than those without
      infection (2.3 +/- 1.3 vs. 0.9 +/- 0.6 mmol/L, respectively; p = 0.003); however,
      no difference in arterial ammonia levels emerged between the two groups (37.7 +/-
      18.6 vs. 37.6 +/- 18.8 micromol/L, respectively). No significant correlation was
      found between gastric juice ammonia concentrations and arterial ammonia levels.
      The data suggest that liver impairment remains crucial in ammonia disposal in
      patients with cirrhosis, whereas H. pylori infection does not seem to play a
      major role in the pathogenesis of hyperammonemia in these patients.

PMID- 11960075
TI  - Rosiglitazone-induced granulomatous hepatitis.
AB  - Granulomatous hepatitis has many causes. Drugs are an important etiologic factor.
      Several oral hypoglycemic agents are available for treatment of type II diabetes.
      Rosiglitazone, a thiazolidinedione, is a newer agent in this class. It has not
      been shown to be hepatotoxic in the premarketing trials. However, a few case
      reports have implicated it as a cause of acute hepatocellular injury. The authors
      report a case of granulomatous hepatitis associated with use of rosiglitazone.
      Liver function tests should be done regularly to monitor patients on this
      medication.

PMID- 11960076
TI  - Losartan-induced hepatic injury.
AB  - Losartan, an angiotensin II receptor antagonist, is widely used for the treatment
      of hypertension. Clinical experience with this drug has demonstrated that it is
      safe. Losartan-induced hepatic toxicity is extremely rare. We report a case of
      severe hepatic toxicity and fibrosis caused by losartan use, and we review four
      previously reported cases. Drug-induced hepatic injury may be seen during the
      treatment of hypertension by losartan and the clinician should be aware of this
      toxicity, especially during the initial phase of treatment.

PMID- 11960077
TI  - Double wire-assisted placement of a nasojejunal feeding tube across duodenal bulb
      stricture to the ligament of Treitz.

PMID- 11960078
TI  - Acute tension hydrothorax: a life-threatening complication of cirrhosis.

PMID- 11960081
TI  - A twin registry study of familial and individual risk factors for trauma exposure
      and posttraumatic stress disorder.
AB  - This study examines the association of individual and familial risk factors with
      exposure to trauma and posttraumatic stress disorder (PTSD) in male twins (N =
      6744) from the Vietnam Era Twin Registry. Independent reports of familial
      psychopathology from co-twins were used to avoid the potential biases of the
      family history method. Risk for exposure to traumatic events was increased by
      service in Southeast Asia, preexisting conduct disorder, preexisting substance
      dependence, and a family history of mood disorders whose effects appear to be
      partly genetic. Preexisting mood disorders in the individual were associated with
      decreased odds of traumatic exposure. Risk of developing PTSD following exposure
      was increased by an earlier age at first trauma, exposure to multiple traumas,
      paternal depression, less than high school education at entry into the military,
      service in Southeast Asia, and preexisting conduct disorder, panic disorder or
      generalized anxiety disorder, and major depression. Results suggest the
      association of familial psychopathology and PTSD may be mediated by increased
      risk of traumatic exposure and by preexisting psychopathology.

PMID- 11960082
TI  - Heritability of social anxiety-related concerns and personality characteristics:
      a twin study.
AB  - Negative evaluation fears figure prominently in the cognitive psychology of
      patients with social phobia. In this study, we examine the heritability of
      negative evaluation fears by using a twin sample. The authors also examine the
      relationships between negative evaluation fears and personality dimensions
      relevant to social phobia. Scores on the brief version of the Fear of Negative
      Evaluation Scale (BFNE) were examined in a sample of 437 (245 monozygotic and 192
      dizygotic) twin pairs. Biometrical model fitting was conducted by using standard
      statistical methods. Genetic and environmental correlations with personality
      dimensions (from the Dimensional Assessment of Personality Pathology-Basic
      Questionnaire) were also calculated. Broad heritability estimate of the BFNE was
      48%. Additive genetic effects and unique environmental effects emerged as the
      primary influences on negative evaluation fears. Genetic correlations between
      BFNE scores and the submissiveness, anxiousness, and social avoidance facets of
      the Dimensional Assessment of Personality Pathology-Basic Questionnaire were high
      (r(g) =.78 to.80). A cognitive dimension central to the phenomenology (and,
      perhaps, cause) of social phobia, the fear of being negatively evaluated, is
      moderately heritable. Moreover, the same genes that influence negative evaluation
      fears appear to influence a cluster of anxiety-related personality
      characteristics. Implications and limitations of these findings are discussed.

PMID- 11960083
TI  - Social anxiety spectrum: gender differences in Italian high school students.
AB  - Gender differences in the social anxiety spectrum and their correlation with
      other psychopathological features were analyzed in 520 students by using two
      questionnaires: the Social Anxiety Spectrum Self-Report (SHY-SR), which explores
      social anxiety spectrum, and the General Spectrum Measure (GSM), which explores
      panic-agoraphobia, mood, obsessive-compulsive, and eating-behavior features. Mean
      SHY-SR total score was significantly higher in women than in men, and gender
      differences were particularly pronounced for interpersonal sensitivity domain.
      Likewise, GSM scores were higher in women, except for the manic section. The SHY
      SR domains correlated significantly with all GSM sections, except for the manic
      section. In conclusion, women reported more symptoms than men (who belonged to
      different psychopathologic dimensions) and displayed a profile of social anxiety
      spectrum that differs quantitatively but not qualitatively from the men's
      profile. The correlation between social anxiety spectrum and other
      psychopathological features mirrors previous findings concerning the high
      comorbidity of axis-I social anxiety disorder.

PMID- 11960084
TI  - Health functioning impairments associated with posttraumatic stress disorder,
      anxiety disorders, and depression.
AB  - Although anxiety disorders have been associated with impairments in self-reported
      health functioning, the relative effect of various anxiety disorders has not been
      studied. We compared health functioning of patients with a principal diagnosis of
      posttraumatic stress disorder (PTSD), panic disorder (PD), generalized anxiety
      disorder (GAD), and major depressive disorder (MDD). Patients with PTSD and MDD
      were equally impaired on overall mental health functioning, and both were
      significantly worse than patients with PD and GAD. PTSD was associated with
      significantly worse physical health functioning relative to PD, GAD, and MDD.
      Hierarchical regression showed that the association of PTSD with physical health
      functioning was unique and was not caused by the effects of age, depression, or
      comorbid anxiety disorders. Both PTSD and comorbid anxiety accounted for unique
      variance in mental functioning. These results highlight the association of PTSD
      with impaired physical and mental functioning and suggest that effective
      treatment of PTSD may affect overall health.

PMID- 11960085
TI  - Caregiver burden in recent-onset schizophrenia and spectrum disorders: the
      influence of symptoms and personality traits.
AB  - Earlier studies that used two symptom dimensions indicate that the caregiver
      burden for patients with schizophrenia is significantly determined by their
      negative symptoms. The purpose of this study is to examine the relationship
      between symptom severity in recent-onset schizophrenia and caregiver burden in a
      more differentiated way (i.e., five-symptom dimensions). Based on previous
      research, which shows that patients' personality traits influence the course of
      schizophrenia, we theorize that personality traits could also influence caregiver
      burden. So far, this hypothesis has never been studied. Therefore, the second
      purpose of this study is to examine whether patients' personality traits would
      contribute to caregiver burden. The results of this study showed that the
      disorganization symptom component was the predicting variable of the subscales
      supervision, tension, urging, distress, and the overall amount of caregiver
      burden in a linear regression analysis. Personality traits of patients played no
      substantial role in caregiver burden. These findings suggest that
      psychoeducational programs should address the severity of disorganization
      symptoms to reduce caregiver burden in the early phase of schizophrenia.

PMID- 11960086
TI  - Predictors of stable personality disorder diagnoses in outpatients with remitted
      depression.
AB  - This study examined the stability of comorbid personality disorder diagnoses once
      an outpatient's depression remitted. The sample consisted of 75 outpatients who
      responded to treatment in an 8-week acute treatment phase for depression, who met
      criteria for remission throughout a 26-week continuation phase, and who completed
      a personality assessment (Structured Clinical Interview for DSM-III-R-axis II
      Disorders) at the beginning and at the end of each treatment phase. The authors
      found that after a major depressive disorder is successfully treated, personality
      disorder diagnoses remain stable across time during continuation treatment.
      Gender was the only potential predictor variable that was significant: the
      proportion of men who had a stable personality disorder diagnosis in cluster A or
      cluster B was significantly greater than the proportion of women who had a stable
      personality disorder diagnosis in these two clusters. Among women, those with any
      stable personality disorder had a significantly longer duration of the current
      major depressive disorder compared with those who never met criteria for any
      personality disorder; this was also true for women with a cluster C personality
      disorder diagnosis.

PMID- 11960089
TI  - Completion of advance directives for general health care among inpatients with
      schizophrenia.

PMID- 11960087
TI  - Predictors of posttraumatic stress in civilians 1 year after air attacks: a study
      of Yugoslavian students.
AB  - The level of posttraumatic stress, other psychological symptoms, and potential
      predictors were assessed in 139 medical students 1 year after experiencing air
      attacks in Belgrade, Yugoslavia. Eleven percent of the students showed high
      levels of posttraumatic stress (scores > 34) on the Impact of Event Scale; lower
      degrees of intrusion symptoms were reported by 32% of the students and avoidance
      symptoms were reported by 45%. Although gender, distress during previous
      stressful events, and exposure to trauma during the attacks were all of some
      predictive value, distress during the attacks was the best predictor for
      symptoms. This association remained significant when the influence of other
      psychological symptoms was controlled. The type of previous stressful events
      interacted with the degree of exposure to trauma during the attacks in predicting
      avoidance symptoms, but not intrusion symptoms. The findings suggest that
      predictors for high and low thresholds of symptoms may be similar. The quality of
      previous stressful events can modify the response to subsequent trauma.

PMID- 11960090
TI  - Defense mechanisms in Chinese patients with comorbid anxiety and depression.

PMID- 11960091
TI  - Familial and personal handedness in phobic anxiety disorder.

PMID- 11960117
TI  - What's in a name?

PMID- 11960118
TI  - I am a Nurse.

PMID- 11960119
TI  - End-of-life issues in the emergency department.

PMID- 11960120
TI  - Hand creams and medical gloves.

PMID- 11960121
TI  - Millipedes--health consequences.

PMID- 11960122
TI  - A comparison of nurses' needs/concerns and hospital disaster plans following
      Florida's Hurricane Floyd.
AB  - INTRODUCTION: The idea for this study was inspired by the response to Hurricane
      Floyd. Nurses are relied upon and expected to fulfill responsible roles during
      disaster situations, but little is known about the needs or concerns that nurses
      experience when they meet expectations and function as disaster responders.
      METHODS: Official copies of disaster protocols from 4 area hospitals were
      reviewed, and 4 focus groups consisting of ED nurses from respective hospitals
      provided information about nurses' concerns or needs in response to Hurricane
      Floyd. RESULTS: Of primary importance to nurses was family safety, pet care, and
      personal safety while at work. Secondary concerns were basic needs such as food,
      water, sleep, shelter, and rest. Group commitment levels to providing care during
      disaster situations varied greatly. Participants requested that hospital policy
      revisions address work assignments, pay/financial compensation, flexibility for
      extenuating circumstances, pet care, family sheltering, and provision of basic
      needs. DISCUSSION: It is not sufficient for a few key officials and planners to
      know their roles and responsibilities during a disaster; the roles of everyone
      involved must be clearly understood. Many participants described their conflict
      as family commitment versus professional obligation. We identified several areas
      of concerns in our interviews, and those areas have been clearly defined in the
      revised protocols. Other areas have yet to be addressed.

PMID- 11960123
TI  - The effect of standard care, ibuprofen, and distraction on pain relief and
      patient satisfaction in children with musculoskeletal trauma.
AB  - INTRODUCTION: The purpose of this study was to determine the effectiveness of
      nursing interventions in decreasing pain for children with minor musculoskeletal
      trauma and moderate pain and to examine patient satisfaction. METHODS: Children
      were assigned to 1 of 3 intervention groups: (1) standard care (ice, elevation,
      and immobilization) only; (2) standard care and ibuprofen; or (3) standard care
      and distraction. Children were monitored for pain ratings for 60 minutes.
      Children who sustained minor musculoskeletal trauma within the past 24 hours and
      presented with pain ratings of 2 or greater using the 0-5 Wong/Baker faces scale
      were included. Two patient satisfaction questions were asked of parents upon
      their child's discharge from the emergency department. RESULTS: A statistically
      significant decrease in pain for all patients (76) occurred at 30 minutes (F =
      4.39, P <.05) and was maintained at 60 minutes. The distraction group
      demonstrated a statistically significant reduction in pain compared with the
      other groups at 30 minutes; this reduction was maintained at 60 minutes (F =
      47.07, P <.05). Parents of only 6 children expressed dissatisfaction with overall
      pain management. Twelve percent of children who were not in the group receiving
      medication received analgesics while in the emergency department. At discharge,
      only 37% of children with fractures and/or sprains had received medications for
      pain. DISCUSSION: Children with musculoskeletal trauma may be under-medicated.
      Distraction techniques can be an effective adjunct to analgesia for children with
      musculoskeletal pain in the emergency department and should be made available.
      Ibuprofen may not be an effective analgesic for children with these injuries;
      stronger analgesics may be required.

PMID- 11960124
TI  - Characteristics and treatment of patients with heart failure in the emergency
      department.
AB  - INTRODUCTION: This study was conducted to develop a detailed profile of patients
      who come to the emergency department for heart failure treatment. METHODS:
      Patient interviews were supplemented by medical record reviews in a convenience
      sample of 57 participants. A structured interview guide included data concerning
      patient characteristics and ED treatment. RESULTS: Participants used a variety of
      self-care strategies before coming to the emergency department. Many of the
      patients studied (25%) reported barriers to medication adherence, such as memory
      problems and lack of knowledge regarding self-administration. The most frequently
      reported symptoms were breathing difficulties (88%), chest discomfort (35%), and
      fatigue (16%). Seventy-four percent of the participants were classified as
      specific activity scale class III or IV, indicating moderate to severe functional
      limitation. Mean quality of life at the time of interview was 5.1 (on a 1 to 10
      scale). Length of stay was < or = 2 days for 33%. DISCUSSION: A number of the
      findings of this study have implications for ED nurses. For example, almost one
      third of the patients studied had not received directions for a low-sodium diet
      during hospitalization, when fluid volume overload with sodium retention was the
      most common cause of hospitalization in a study of patients with decompensated
      heart failure. Hospital lengths of stay of no more than 2 days suggest that early
      detection and treatment of acute heart failure may reduce the need for ED visits
      for some patients. Patients need education and support with self-help strategies
      and need to better understand the administration of their medication.

PMID- 11960125
TI  - Understanding the newer automated external defibrillator devices:
      electrophysiology, biphasic waveforms, and technology.

PMID- 11960126
TI  - Acuity-based ED nurse staffing: a successful 5-year experience.

PMID- 11960128
TI  - Suspicious powder is everywhere.

PMID- 11960130
TI  - Spring--what better time to teach bike and helmet safety? Ideas for posters and
      community events.

PMID- 11960131
TI  - ED physician fined under EMTALA for refusing to treat intoxicated patient.

PMID- 11960133
TI  - A consortium to educate new ED nurses: Portland, Oregon's experience.

PMID- 11960134
TI  - Night shifts and breast cancer risk: policy implications.

PMID- 11960135
TI  - Excellence in forensic practice: a clinical ladder model for recruiting and
      retaining sexual assault nurse examiners (SANEs).

PMID- 11960136
TI  - Massive transfusion: don't stop.

PMID- 11960137
TI  - An 18-year-old woman with unexplained vision loss.

PMID- 11960139
TI  - Primary cutaneous nocardiosis with epidural abscess caused by Nocardia
      brasiliensis: a case report.
AB  - Dissemination of primary cutaneous nocardiosis is a rare event. An interesting
      case of a 20 year old female labourer with progressive weakness in both the lower
      limbs and large multiple subcutaneous abscesses over the back, since 4 years, is
      presented. MRI showed an epidural abscess compressing the cord. Histopathology of
      skin lesions suggested a chronic suppurative lesion. Microbiological tests on the
      aspirate from the skin lesion identified the causative organism as Nocardia
      brasiliensis.

PMID- 11960141
TI  - New hopes for neurologically disabled.

PMID- 11960142
TI  - Idiopathic hypertrophic cranial pachymeningitis: easy to suspect, difficult to
      prove.

PMID- 11960143
TI  - Moyamoya disease: a review.
AB  - Moyamoya is probably an inherited vasocclusive disease first described in Japan
      and now reported from all over the world. Genetic linkage studies and study of
      the factors possibly involved in its pathogenesis have shed new light on this
      disease. There is some suggestion that the pathogenesis may vary between races. A
      number of revascularization procedures have been devised. There is still
      controversy regarding the timing and the type of surgery. Functional MRI and PET
      scanning may provide more objective criterion on the outcome of these procedures.
      Neuropsychological studies may also be of use in judging the benefits of surgery.
      In this review, some of the recent advances in the study of the genetics and
      pathogenesis of the disease are reviewed and the clinical manifestation and the
      role of surgery are discussed. Relative lack of literature from outside Japan and
      the Korean peninsula has hampered the understanding of the disease in other
      countries.

PMID- 11960144
TI  - Selection of ideal candidates for epilepsy surgery in developing countries.
AB  - In order to become cost-effective, epilepsy surgery centers in developing
      countries will have to achieve excellent results by selecting candidates destined
      to have a seizure-free outcome using locally available limited technology and
      expertise, without compromising on patient safety. Our experience illustrates
      that this goal can be accomplished by selecting patients, whose epileptogenic
      zone can be unquestionably established, based on history, magnetic resonance
      imaging, and interictal and ictal scalp electroencephalogram findings. Patients
      with mesial temporal lobe epilepsy, and those with circumscribed potentially
      epileptogenic lesions belong to this category. A stepwise approach by reserving
      more difficult to treat patients to later date as experience develops, or by
      referring them to a better-equipped center, will help each center to understand
      its capabilities and limitations and to move forward. It would be essential to
      work with and educate the local public and professionals, if the epilepsy surgery
      program in a developing region were to have a lasting impact, It is encouraging
      to note that, despite major challenges, in the last one-decade, several epilepsy
      centers in the developing world have not only successfully implemented epilepsy
      surgery programs, but also have produced results comparable to that from
      developed countries at a fractional cost.

PMID- 11960145
TI  - A radiological evaluation of allografts (ethylene oxide sterilized cadaver bone)
      and autografts in anterior cervical fusion.
AB  - Serial roentgenograms of 40 patients who had 70 cervical intervertebral spaces
      grafted with ethylene oxide sterilized cadaver bone and 28 patients who received
      44 iliac crest auto grafts for anterior cervical spine fusion, were studied. The
      radiological evaluation was made on the basis of settlement of intervertebral
      spaces, fusion rate, delayed union, non-union, graft collapse and extrusion of
      the graft. Indigenous methodologies were designed for the assessment of
      settlement of grafted intervertebral spaces in percentage. Disc space settlement
      was more common in autografts (93% cases) than in allografts (80% cases). The
      average percentage of settlement of intervertebral disc space (S%) was 22 in
      autografts and 28 in allografts during the first four months. By the end of eight
      months, allograft disc spaces settle more. No significant difference was noted in
      fusion rate at the end of one year viz. allografts (90% cases) and autografts
      (93% cases). Autograft and allograft (ethylene oxide sterilized cadaver bone) are
      equally useful in anterior cervical spine fusions.

PMID- 11960147
TI  - Sarcoglycanopathies: a report of 25 cases.
AB  - Twenty five patients with sarcoglycanopathies were studied prospectively. 21 of
      them had mild phenotype. Muscle involvement was more pronounced in adductor and
      flexor groups of muscles of the limbs, hip adductor muscles being the weakest.
      The selective and differential weakness between weak hip adductors and stronger
      hip abductors resulted in the hip abduction sign in 64% of cases. Distal muscle
      involvement in lower limbs was seen in 92% of cases, but was mild and late in the
      course of the disease. 44% patients had winging of scapulae. Immunocytochemistry
      showed multiple sarcoglycan deficiencies in 84% patients. Primary beta and delta
      sarcoglycanopathy was seen in the remaining 16% cases. Secondary dystrophin
      reduction was seen in 44% patients and correlated with beta sarcoglycan
      deficiency but not with functional disability.

PMID- 11960146
TI  - Microneural anastomosis with fibrin glue: an experimental study.
AB  - An experimental study was designed to compare the histological analysis of nerve
      anastomosis with 10-0 microsurgical sutures and fibrin adhesive. Wistar albino
      rats' sciatic nerves were transected and repaired either with fibrin adhesive
      Beriplast P (M/s Centeon-Cadila Health Care) or with 10-0 monofilament
      microsutures. Histological assessment was performed at 10, 20, 30, 60 and 90 days
      after surgery. Functional recovery of the sciatic nerves started at two months
      and was near normal by three months. Separation of the stumps did not occur in
      any of the glued nerves. Histological evaluation showed no appreciable difference
      in the outcome of nerve regeneration after microsurgical repair using sutures or
      fibrin tissue adhesive. However, inflammation and granuloma formation were
      appreciated at the suture site, which presented a focal hindrance to myelin and
      axonal regeneration. Fibrin glueing is attractive for clinical purposes, since it
      is simpler and less time consuming than suturing.

PMID- 11960148
TI  - The lateralizing significance of version of head and dystonic limb posturing in
      epileptic seizures.
AB  - Several clinical signs have been described for lateralization and localization of
      seizure focus in complex partial seizures; however, the specificity of each of
      these has been widely debated upon. The present study was done to evaluate
      'dystonic unilateral limb posturing' and 'versive head movements' for
      lateralization and localization of epileptic foci in patients with intractable
      partial complex seizures, being investigated with long term Video-EEG monitoring.
      Fifteen patients with 46 seizures, studied with long term Video EEG, had either
      one or both of these signs. The video recordings of the clinical behaviour were
      noted and later compared with the corresponding EEG. Unilateral dystonic limb
      posturing and versive head movements had good lateralising value in complex
      partial seizures, suggestive of temporal lobe origin, contralateral to the
      seizure focus, with a specificity of 87.5% and 86% respectively. In addition,
      turning of the whole body to one side was associated with a contralateral seizure
      focus in 100% cases. Appendicular automatisms were found to be of no lateralising
      significance, as they occurred on either side with equal frequency. These motor
      phenomena should, therefore, be enquired about in detail, during history taking
      for lateralization or localization of seizure focus.

PMID- 11960149
TI  - Prognostic factors influencing the outcome of thalamic glioma.
AB  - Retrospective analysis of 27 patients of thalamic glioma including adults and
      children treated over a period of 7 years from 1991-1997 was done. The study
      group included 19 males and 8 females; 9 patients were less than 15 years and 18
      patients more than 15 years of age at the time of diagnosis. The commonest
      symptoms were headache and vomiting. 12 patients underwent VP shunt as an initial
      procedure and 7 underwent total or partial surgical resection. Confirmed
      histopathological examination was possible in 16 patients; while 12 had low grade
      astrocytoma, 4 cases had high grade histology. All patients were treated with
      radiotherapy to a total dose of 50-60 Gy in 25-30 fractions. Median follow up was
      9.63 months. The disease free survival in these patients was 28% at 2 years.
      Prognostic factors which included age, sex, duration of symptoms, surgical
      procedures, histology and radiotherapy dose were evaluated for significance. A
      subtotal resection conferred a better prognosis.

PMID- 11960150
TI  - CSF beta-1 Globulin--a potential marker in differentiating multiple sclerosis and
      acute disseminated encephalomyelitis: a preliminary study.
AB  - The exact diagnosis of demyelinating diseases is an enigma even in the best
      neurological centres. In the present study, the potential role of differential
      CSF proteins has been critically evaluated in differentiating multiple sclerosis
      (MS) and acute disseminated encephalomyelitis (ADEM). Cellulose acetate
      electrophoresis was carried out on CSF and serum samples of 14 MS patients, 23
      ADEM patients and 30 controls. There was no statistically significant difference
      between serum electrophoresis of controls and MS patients. However, in case of
      CSF electrophoresis there was a statistically significant decrease in beta-1
      fraction in 92.2% of MS patients (p=0.01). A comparison between serum
      electrophoresis of controls and ADEM patients indicated a statistically
      significant decrease in serum albumin in 87% patients and an increase of alpha-2
      globulin in 73.9%. There was no statistically significant difference between CSF
      electrophoresis of controls and ADEM patients except for the prealbumin fraction
      which was raised in 60.9% of patients. No statistically significant difference
      was seen between the serum electrophoresis of ADEM and MS patients. However, on
      comparing CSF electrophoresis, it was seen that beta-1 fraction was significantly
      higher in ADEM patients (p<0.05). The predictive value of beta-1 fraction in
      differentiating MS and ADEM was then evaluated. The negative predictive value was
      100% indicating that all samples with a beta-1 fraction of>6.5% cannot be
      diagnosed as MS. The significant decrease in beta-1 fraction in MS patients may
      prove to be an early indicator in differentiating between MS and ADEM patients.

PMID- 11960151
TI  - Hypertrophic pachymeningitis: varied manifestations of a single disease entity.
AB  - Hypertrophic pachymeningitis is a unique clinical entity characterised by
      fibrosis and thickening of the duramater with resulting neurological dysfunction.
      Three cases of this entity are described. Presenting features were headaches and
      cranial neuropathies in two patients and predominantly cerebellar dysfunction in
      the third. One of the patients also had evidence of spinal involvement. Lower
      cranial nerves were chiefly involved in two patients whereas optic nerve was the
      predominantly affected nerve in one. Except for the presence of rheumatoid
      arthritis in one of the patients, we could not document clinical or biochemical
      evidence of any predisposing infective, inflammatory or infiltrative condition in
      the other two. All three patients had characteristic changes on imaging
      suggestive of thickened and enhancing duramater. Although variable steroid
      responsiveness was seen in all the three patients, tendency towards steroid
      dependence was evident. The clinical presentations, causes, radiological
      features, management options and differential diagnosis of this unique clinical
      syndrome have been discussed.

PMID- 11960152
TI  - Idiopathic hypertrophic cranial pachymeningitis.
AB  - Idiopathic hypertrophic cranial pachymeningitis is a rare form of fibrosing
      chronic inflammatory process of unknown etiology, which causes thickening of the
      intracranial dura mater. We present four patients with hypertrophic cranial
      pachymeningitis who presented with chronic headache and cranial nerve palsies.
      The diagnosis of idiopathic hypertrophic cranial pachymeningitis was based on
      neuroimaging findings of thickened enhancing dura, exclusion of known causes and
      histopathologic findings compatible with nonspecific inflammation in the
      meningeal biopsies. Corticosteroid therapy was effective in all cases in inducing
      a complete or partial remission of the neurologic symptoms and signs. We describe
      the clinical, radiological and pathological features of idiopathic hypertrophic
      cranial pachymeningitis and discuss the relationship of this entity with other
      inflammatory fibrosclerotic disorders to explain the pathogenesis. A high index
      of suspicion, prompt confirmation of the diagnosis by meningeal biopsy, and early
      institution and long-term maintenance of steroid therapy may help to prevent
      irreversible neurologic sequelae, especially blindness.

PMID- 11960153
TI  - Correlation of serum and salivary carbamazepine concentration in epileptic
      patients: implications for therapeutic drug monitoring.
AB  - Therapeutic drug monitoring (TDM) of carbamazepine (CBZ) in saliva is an
      attractive alternative, because its collection is painless, non-invasive and
      simpler than drawing blood. Salivary drug levels, also closely reflect the free
      drug concentration. The aim of the study was to evaluate the suitability of
      saliva in routine TDM of CBZ in adult epileptic patients. Blood and saliva
      samples were taken simultaneously at 0 hours and 24 hours of CBZ dosing from 31
      epileptic patients, receiving CBZ monotherapy for three or more months. Levels of
      CBZ in both these fluids were measured by high performance liquid chromatography.
      Strong and highly significant correlation was found between serum and salivary
      CBZ concentration (r = 0.659, p<0.001). Estimation of CBZ level in saliva is thus
      a practicable, valid and convenient method of TDM in epileptic patients.

PMID- 11960154
TI  - Dexamethasone therapy for bacterial meningitis in adults: a double blind placebo
      control study.
AB  - Routine use of steroids in the treatment of bacterial meningitis remains
      controversial. A prospective placebo controlled double blind study of
      dexamethasone was carried out in 40 patients (age>10 years) of acute bacterial
      meningitis. The patients were randomly assigned to receive either placebo (n=20)
      or dexamethasone (n=20) in addition to injection ceftriaxone 100 mg/kg/day
      (maximum 4 gm/day) for 14 days. Dexamethasone sodium phosphate was given in dose
      of 0.6 mg/kg/day in 4 divided doses, for first 4 days of therapy. First dose of
      dexamethasone was given 15 minutes prior to first dose of ceftriaxone. Baseline
      demographics, clinical and laboratory features of the two groups were similar.
      Clinical improvement of signs of meningeal irritation was rapid in dexamethasone
      group than in the placebo group, but no significant difference was observed
      regarding resolution of fever, headache and vomiting. Secondary fever (mean+/-SD
      15.00), gastrointestinal tract bleeding (mean+/-SD 15.00) and psychiatric
      manifestations (mean+/-SD 10.00) were more common in dexamethasone group.
      Neurological complications and hearing loss were more common and severe in
      placebo group as compared to the dexamethasone group (p<0.05). It is concluded
      that dexamethasone may be beneficial in some aspects of bacterial meningitis, in
      adults. A study with a larger number of cases in each group is recommended.

PMID- 11960155
TI  - Pneumatic splints: fabrication and use in neurorehabilitation.
AB  - Asymmetrical tone and weakness in antagonistic muscles often result in
      misalignment of joint, contractures and deformities. Traditional static splints
      used to prevent these complications are expensive, have to be custom made and
      cannot be used when deformities are marked. Authors describe fabrication and use
      of pneumatic splints, which are economic, safe and easy to apply. These splints
      have wide application in the management of common medical problems in
      neurological rehabilitation like hypotension, edema, pain, spasticity and early
      deformities.

PMID- 11960156
TI  - Omental transplantation for temporal lobe epilepsy: report of two cases.
AB  - The authors present two patients, with poorly controlled temporal lobe epilepsy,
      who received transplants of omental tissue on the anterior perforated space and
      left temporal lobe. At present, 26 months after the operation, the first patient
      has improved about 85 percent; whereas the second patient has complete control of
      seizures nine months after the operation. These clinical results indicate that
      epileptic seizures can be reduced or aborted with this new surgical modality
      (reconstructive technique).

PMID- 11960157
TI  - Primary intraspinal primitive neuroectodermal tumor (PNET): a rare occurrence.
AB  - The concept of primitive neuroectodermal tumors (PNETs) has been evolving for
      many years, as has been its nomenclature. A 5 year old boy presented with pain in
      lower cervicodorsal region and left leg. Preoperative MRI of the spine and
      paravertebral region revealed a hyperintense lobulated lesion extending from D1
      D4 with a large intraspinal and thoracic component. A total removal of tumor was
      achieved via a dorsal laminectomy and right posterolateral thoracotomy. The
      pathological findings were consistent with PNET. Post operative neurological
      examination had been unremarkable. Six months follow up scan showed no
      recurrence. A review of the literature shows that only 18 cases of primary
      intraspinal PNETs have been reported to date and the present case is exclusive,
      in which the tumor was thoracic, extradural in location and the child is alive at
      8 months of follow up, with no evidence of tumor recurrence/metastasis. Primary
      intraspinal PNETs are rare tumors and carry a poor prognosis. Newer modalities of
      treatment should be tried to improve survival.

PMID- 11960158
TI  - High cervical and lumbar canal stenosis of varied etiology: a case report.
AB  - Developmental stenosis without any significant spondylotic changes frequently
      occurs at C3 vertebra or below, and typically extends to C6-C7. However, high
      cervical focal canal stenosis is unusual. A case of cervical canal segmental
      stenosis at C2-3 level in addition to a developmental stenosis of the lumbar
      region, in a 45 year old male, has been presented in this article. The dynamics
      of the spinal canal in relation to the likely pathology of such conditions are
      reviewed. We speculate that focal segmental stenosis in the high cervical region
      may be due to a possible premature fusion of the neurocentral synchondrosis of
      the cartilage, or due to an abnormal rotary biomechanics which can result in
      facetal hypertrophy.

PMID- 11960159
TI  - Familial trigeminal neuralgia.
AB  - Familial trigeminal neuralgia is infrequent. A report of a couple and their son
      being afflicted by this malady is presented. The clinical features, radiological
      findings and surgical management are discussed and literature reviewed.

PMID- 11960160
TI  - Cervico thoracic junction spinal tuberculosis presenting as radiculopathy.
AB  - A case of cervico thoracic junctional area spinal tuberculosis presenting as
      painful radiculitis of the upper extremity is reported. The predominant symptom
      of radicular pain and muscle weakness in the hand, along with a claw deformity,
      led to considerable delay in diagnosis. The presence of advanced bone destruction
      with severe instability was demonstrated on the MRI scan done later. Surgical
      management by radical anterior debridement and fusion, along with chemotherapy,
      led to resolution of the upper extremity symptoms. The brachial plexus
      radiculopathy secondary to tuberculosis has not been reported. The absence of
      myelopathic signs even in the presence of advanced bone destruction, thecal
      compression and instability is uncommon in adults.

PMID- 11960161
TI  - Syringomyelia as a cause of limb hypertrophy.
AB  - A case of limb hypertrophy secondary to syringomyelia is presented.

PMID- 11960163
TI  - Stiff person syndrome and myasthenia gravis.
AB  - Association of stiff person syndrome, an immune related disorder of anterior horn
      cells and myasthenia gravis an endplate disorder with similar pathogenesis, is
      rare. This communication documents this association in the Indian literature for
      the first time.

PMID- 11960162
TI  - Atypical manifestation of dural arteriovenous fistula.
AB  - A case of secondary dural arteriovenous fistula presenting as infantile stroke,
      in a fifteen month old boy, is reported. The initial impression on CT scan in
      this case was misleading, due to the atypical appearance of the pathological
      periventricular blood vessels, interpreted as periventricular calcification.

PMID- 11960164
TI  - Scorpion bite and multiple cerebral infarcts.
AB  - Multiple cerebral infarcts, bilateral optic neuropathy with limb ischemia,
      following scorpion bite is documented. Vasospasm and autonomic storm due to
      envenomation is a plausible explanation for this symptom complex.

PMID- 11960165
TI  - A case of emotional facial palsy with ipsilateral anterior inferior cerebellar
      artery territory infarction.
AB  - Emotional facial palsy (EFP) commonly results from anterolateral thalamic or
      striatocapsular infarcts. Its occurrence in brainstem lesions is uncommon, with
      previously reported cases being restricted to superior cerebellar artery
      infarction (3 cases). We report an unusual case of EFP ipsilateral to an anterior
      inferior cerebellar artery infarction, which opens new insights into the facial
      corticobulbar tract pathway.

PMID- 11960166
TI  - Polyglandular endocrinopathy in myotonic dystrophy: letter to editor.

PMID- 11960167
TI  - Preliminary observations on valproate and cystic ovaries: letter to editor.

PMID- 11960168
TI  - Leber's idiopathic stellate neuroretinitis: letter to editor.

PMID- 11960169
TI  - Rare shunt complication : letter to editor.

PMID- 11960170
TI  - Acyclovir induced extrapyramidal symptoms : letter to editor.

PMID- 11960171
TI  - Subclavian steal syndrome: neuroimage.

PMID- 11960177
TI  - A taxonomic bibliography of the South American snakes of the Crotalus durissus
      complex (Serpentes, Viperidae).
AB  - A survey is made of the taxonomic literature on South American rattlesnakes
      (genus Crotalus, family Viperidae). Two main areas are emphasized: the
      attribution of the names proposed in the eighteenth century by Linnaeus and
      Laurenti, and the current scheme of division in subspecies. The attribution of
      names is examined based on the original descriptions and on relevant previous and
      contemporary literature. The presently adopted scheme, proposed by Klauber (1941,
      1972) is found not entirely satisfactory, but reasonable enough--besides being
      hallowed by use. The scheme of geographical differentiation, intrinsically
      important and with broad practical implications (differentiation of the venom) is
      found to be the culmination of a long series of deficient analyses, and in urgent
      need of proper investigation.

PMID- 11960178
TI  - The lizard cerebral cortex as a model to study neuronal regeneration.
AB  - The medial cerebral cortex of lizards, an area homologous to the hippocampal
      fascia dentata, shows delayed postnatal neurogenesis, i.e., cells in the medial
      cortex ependyma proliferate and give rise to immature neurons, which migrate to
      the cell layer. There, recruited neurons differentiate and give rise to zinc
      containing axons directed to the rest of cortical areas, thus resulting in a
      continuous growth of the medial cortex and its zinc-enriched axonal projection.
      This happens along the lizard life span, even in adult lizards, thus allowing one
      of their most important characteristics: neuronal regeneration. Experiments in
      our laboratory have shown that chemical lesion of the medial cortex (affecting up
      to 95% of its neurons) results in a cascade of events: first, massive neuronal
      death and axonal-dendritic retraction and, secondly, triggered ependymal
      neuroblast proliferation and subsequent neo-histogenesis and regeneration of an
      almost new medial cortex, indistinguishable from a normal undamaged one. This is
      the only case to our knowledge of the regeneration of an amniote central nervous
      centre by new neuron production and neo-histogenesis. Thus the lizard cerebral
      cortex is a good model to study neuronal regeneration and the complex factors
      that regulate its neurogenetic, migratory and neo-synaptogenetic events.

PMID- 11960182
TI  - Shamanism or science?
AB  - The interconnection of the three organismic levels, metabolism, morphology, and
      biogeography, can now be amplified into a multipart architecture, introducing
      plant bioactivity through ethnobotany-oriented descriptions. Only via such an
      integrative model, the diverse organismic levels can be connected within a more
      holistic, realistic scheme. Construction of qualitative and quantitative models
      via evolutionarily conceived implantation into dahlgrenograms and Sporne indices,
      allows ethnobotany to acquire predictive validity. The coherence of such systems
      was demonstrated by comparison of the vast ethnobotanical Brazilian database by
      Pio Correa with relatively very minute databases referring to three Amazonian
      Indian societies.

PMID- 11960179
TI  - Structure and anticoagulant properties of sulfated glycosaminoglycans from
      primitive Chordates.
AB  - Dermatan sulfates and heparin, similar to the mammalian glycosaminoglycans, but
      with differences in the degree and position of sulfation were previously isolated
      from the body of the ascidian Styela plicata and Ascidia nigra. These differences
      produce profound effects on their anticoagulant properties. S. plicata dermatan
      sulfate composed by 2-O-sulfated alpha-L-iduronic acid and 4-O-sulfated N-acetyl
      beta-D-galactosamine residues is a potent anticoagulant due to a high heparin
      cofactor II activity. Surprisingly, it has a lower potency to prevent thrombus
      formation on an experimental model and a lower bleeding effect in rats than the
      mammalian dermatan sulfate. In contrast, A. nigra dermatan sulfate, also enriched
      in 2-O-sulfated alpha-L-iduronic acid, but in this case sulfated at O-6 of the N
      acetyl-beta-D-galactosamine units, has no in vitro or in vivo anticoagulant
      activity, does not prevent thrombus formation but shows a bleeding effect similar
      to the mammalian glycosaminoglycan. Ascidian heparin, composed by 2-O-sulfated
      alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (75%) and alpha-L-iduronic
      acid, N- and 6-O-sulfated glucosamine (25%) disaccharide units has an
      anticoagulant activity 10 times lower than the mammalian heparin, is about 20
      times less potent in the inhibition of thrombin by antithrombin, but has the same
      heparin cofactor II activity as mammalian heparin.

PMID- 11960183
TI  - Pharmaceuticals from natural products: current trends.
AB  - The use of products extracted from plants for medicinal purposes can be traced to
      the beginnings of civilization and up until the end of the nineteenth century
      natural products were the principal source of medicines. Since then their
      relative importance has oscillated according to the strategies of large
      pharmaceutical companies. Now that these strategies are changing, there are new
      opportunities for countries like Brazil, in which a large proportion of the
      world's biodiversity is located. There are, however, new circumstances that must
      be taken into consideration: material must be collected by groups which are
      formally authorized to do so and under the conditions of the Convention of
      Biological Diversity, the discovery process is being successively outsourced to
      smaller specialized firms and there is a growing integration with producers of
      cosmetics and phytomedicines.

PMID- 11960184
TI  - Secondary metabolites from marine microorganisms.
AB  - After 40 years of intensive research, chemistry of marine natural products has
      become a mature field. Since 1995, there are signals of decreased interest in the
      search of new metabolites from traditional sources such as macroalgae and
      octocorals, and the number of annual reports on marine sponges stabilized. On the
      contrary, metabolites from microorganisms is a rapidly growing field, due, at
      least in part, to the suspicion that a number of metabolites obtained from algae
      and invertebrates may be produced by associated microorganisms. Studies are
      concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish
      and mainly from marine invertebrates such as sponges, mollusks, tunicates,
      coelenterates and crustaceans. Although it is still to early to define
      tendencies, it may be stated that the metabolites from microorganisms are in most
      cases quite different from those produced by the invertebrate hosts. Nitrogenated
      metabolites predominate over acetate derivatives, and terpenes are uncommon.
      Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated;
      among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids
      predominate.

PMID- 11960185
TI  - A multidisciplinary approach to the study of the fluminense vegetation.
AB  - The fluminense vegetation, more specifically the flora from the Jurubatiba
      restinga has been investigated by a multidisciplinary team of botanists, chemist,
      radiobiologist, insect physiologists and geneticist. Vouchers of 564 specimens
      have been collected, identified, organized in an herbarium, and a database is
      being build up containing, in addition to classical botanical data, chemical data
      and information on the potential economic use either for landscape gardening,
      alternative foods or as medicinal plants. Phytochemical studies of the
      Guttiferae, Clusia hilariana, yielded oleanolic acid and nemorosone. Their
      biological activities against the haematophagous insect Rhodnius prolixus vector
      of Chagas disease have been investigated. Finally, it has been observed that
      aquatic plants possessed high levels of the natural radionuclide polonium-210,
      which seems to be originated mainly from soil rather than from atmospheric
      supply.

PMID- 11960186
TI  - Phytochemical characterization of essential oil from Ocimum selloi.
AB  - Ocimum selloi Benth, a native plant of Brazil, has medicinal uses as anti
      diarrheic, antispasmodic and anti-inflammatory product. The yield of essential
      oils of the inflorescences, containing flowers and seeds, was 0.6%, and the yield
      of leaves, collected in two different seasons, was 0.25% (June 2000) and 0.20%
      (January 2001), respectively. The essential oils of the inflorescences and leaves
      presented as major constituents trans-anethol (41.34%, 45.42%, 58.59%) and methyl
      chavicol (27.10%, 24.14%, 29.96%).

PMID- 11960187
TI  - Semiquantitative mercury determination in fish: a tool for poisoning prevention.
AB  - Human exposure to mercury intoxication through contaminated fish ingestion has
      been well studied, mainly among Japanese population. The Brazilian population,
      particularly in the Amazon region, is now in focus due to findings of fish
      contamination. Major health impacts caused by mercury affect mostly people who
      have a regular fish diet. A continuous checking for mercury content in the most
      consumed fish could prevent human intoxication. A simple, non-instrumental method
      to allow a continuous checking of the mercury content in fish was developed.
      Based on this method, we are proposing a prevention action where community agents
      can be trained to perform fish analysis. Technical Schools and Universities
      located nearby the affected areas would be in charge of quality control programs
      for the fish analysis as well as for the selection, training and update for
      operators.

PMID- 11960188
TI  - The 42-kDa coat protein of Andean potato mottle virus acts as a transcriptional
      activator in yeast.
AB  - Interactions of viral proteins play an important role in the virus life cycle,
      especially in capsid assembly. Andean potato mottle comovirus (APMoV) is a plant
      RNA virus with a virion formed by two coat proteins (CP42 and CP22). Both APMoV
      coat protein open reading frames were cloned into pGBT9 and pGAD10, two-hybrid
      system vectors. HF7c yeast cells transformed with the p9CP42 construct grew on
      yeast dropout selection media lacking tryptophan and histidine. Clones also
      exhibited beta-galactosidase activity in both qualitative and quantitative
      assays. These results suggest that CP42 protein contains an amino acid motif able
      to activate transcription of His3 and lacZ reporter genes in Saccharomyces
      cerevisiae. Several deletions of the CP42 gene were cloned into the pGBT9 vector
      to locate the region involved in this activation. CP42 constructions lacking 12
      residues from the C-terminal region and another one with 267 residues deleted
      from the N-terminus are still able to activate transcription of reporter genes.
      However, transcription activation was not observed with construction
      p9CP42deltaC57, which does not contain the last 57 amino acid residues. These
      results demonstrate that a transcription activation domain is present at the C
      terminus of CP42 between residues 267 and 374.

PMID- 11960189
TI  - Comparison of the specificity of PCR and the histopathological detection of
      leishmania for the diagnosis of American cutaneous leishmaniasis.
AB  - More precise and rapid diagnostic methods for American cutaneous leishmaniasis
      (ACL) are necessary because of the growing number of cases observed in Brazil,
      including the northeastern region of the State of Sao Paulo. We applied PCR to 54
      skin or mucosal biopsies from patients with a clinical and/or laboratory
      diagnosis of ACL using primers 13A and 13B, with positive results being obtained
      for 82% of the samples. When the PCR results were compared to those of
      histopathological leishmania detection, PCR showed superior results with 81.5%
      sensitivity and 95% CI of 68.0-95.1%. The Montenegro skin test (MST) was positive
      in 88.7% of patients. Since MST cannot be used as a diagnostic tool in endemic
      areas, the present results strongly suggest the use of PCR for the etiological
      confirmation of ACL, with emphasis on the mucosal form.

PMID- 11960190
TI  - c-Myc protein expression is not an independent prognostic predictor in cervical
      squamous cell carcinoma.
AB  - The c-myc protein is known to regulate the cell cycle, and its down-regulation
      can lead to cell death by apoptosis. The role of c-myc protein as an independent
      prognostic determinant in cervical cancer is controversial. In the present study,
      a cohort of 220 Brazilian women (mean age 53.4 years) with FIGO stage I, II and
      III (21, 28 and 51%, respectively) cervical squamous cell carcinomas was analyzed
      for c-myc protein expression using immunohistochemistry. The disease-free
      survival and relapse-rate were analyzed using univariate (Kaplan-Meier) survival
      analysis for 116 women who completed the standard FIGO treatment and were
      followed up for 5 years. Positive c-myc staining was detected in 40% of
      carcinomas, 29% being grade 1, 9% grade 2, and 2% grade 3. The distribution of
      positive c-myc according to FIGO stage was 19% (17 women) in stage I, 33% (29) in
      stage II, and 48% (43) in stage III of disease. During the 60-month follow-up,
      disease-free survival in univariate (Kaplan-Meier) survival analysis (116 women)
      was lower for women with c-myc-positive tumors, i.e., 60.5, 47.5 and 36.6% at 12,
      36, and 60 months, respectively (not significant). The present data suggest that
      immunohistochemical demonstration of c-myc does not possess any prognostic value
      independent of FIGO stage, and as such is unlikely to be a useful prognostic
      marker in cervical squamous cell carcinoma.

PMID- 11960191
TI  - Brain SPECT imaging in Sydenham's chorea.
AB  - The objective of the present study was to determine whether brain single-photon
      emission computed tomography (SPECT) imaging is capable of detecting perfusional
      abnormalities. Ten Sydenham's chorea (SC) patients, eight females and two males,
      8 to 25 years of age (mean 13.4), with a clinical diagnosis of SC were submitted
      to brain SPECT imaging. We used HMPAO labeled with technetium-99m at a dose of
      740 MBq. Six examinations revealed hyperperfusion of the basal ganglia, while the
      remaining four were normal. The six patients with abnormal results were females
      and their data were not correlated with severity of symptoms. Patients with
      abnormal brain SPECT had a more recent onset of symptoms (mean of 49 days)
      compared to those with normal SPECT (mean of 85 days) but this difference did not
      reach statistical significance. Brain SPECT can be a helpful method to determine
      abnormalities of the basal ganglia in SC patients but further studies on a larger
      number of patients are needed in order to detect the phase of the disease during
      which the examination is more sensitive.

PMID- 11960192
TI  - The distribution of presumptive thoracic paraganglionic tissue in the common
      marmoset (Callithrix jacchus).
AB  - The aortic-pulmonary regions (APR) of seven adult marmosets (Callithrix jacchus)
      and the region of the right subclavian artery of a further three marmosets were
      diffusion-fixed with 10% buffered formol-saline solution. In both regions serial
      5 microm sections were cut and stained by the Martius yellow, brilliant crystal
      scarlet and soluble blue method. Presumptive thoracic paraganglionic (PTP) tissue
      was only observed in the APR. PTP tissue was composed of small groups of cells
      that varied in size and number. The distribution of the groups of cells was
      extremely variable, so much so that it would be misleading to attempt to classify
      their position; they were not circumscribed by a connective tissue capsule, but
      were always related to the thoracic branches of the left vagus nerve. The cells
      lay in loose areolar tissue characteristic of this part of the mediastinum and
      received their blood supply from small adjacent connective tissue arterioles.
      Unlike the paraganglionic tissue found in the carotid body the cells in the
      thorax did not appear to have a profuse capillary blood supply. There was,
      however, a close cellular-neural relationship. The cells, 10-15 microm in
      diameter, were oval or rounded in appearance and possessed a central nucleus and
      clear cytoplasm. No evidence was found that these cells possessed a 'companion'
      cell reminiscent of the arrangement of type 1 and type 2 cells in the carotid
      body. In conclusion, we found evidence of presumed paraganglionic tissue in the
      APR of the marmoset which, however, did not show the characteristic histological
      features of the aortic body chemoreceptors that have been described in some non
      primate mammals. A survey of the mediastina of other non-human primates is
      required to establish whether this finding is atypical for these animals.

PMID- 11960193
TI  - Effect of actinomycin D on simian rotavirus (SA11) replication in cell culture.
AB  - Rotaviruses are the major cause of viral diarrhea in humans and animals.
      Actinomycin D (Act D) is an antibiotic that intercalates DNA and therefore
      inhibits DNA-dependent transcription. The current study was carried out to assess
      the influence of Act D on the replication of simian rotavirus (SA11) in cell
      culture. Virus-infected MA-104 cell cultures were studied in the presence of Act
      D at concentrations of 1.25 and 2.5 microg/ml. Treatment of rotavirus-infected
      cells with 2.5 microg/ml Act D 48 h post-infection reduced the cytoplasmic
      metachromasia after staining with acridine orange by 25%. Viral RNA labeled with
      3H-uridine in the presence of the drug was separated by polyacrylamide gel
      electrophoresis. Viral RNA replication was not affected by Act D, but increased
      3H-uridine uptake was demonstrable by infected cells in the presence of the drug.
      This possibly was due to the inhibition of cellular RNA synthesis by Act D, which
      thus enhances incorporation of the radionuclide into the viral RNA. Act D reduced
      the number of infected cells presenting virus-specific fluorescence 48 h post
      infection by more than 50%. These data suggest that Act D may have complexed with
      viral RNA and prevented newly synthesized mRNA from being translated, but may not
      have prevented early replication.

PMID- 11960194
TI  - Effects of elevated calcium on motor and exploratory activities of rats.
AB  - The effects of serum and brain calcium concentration on rat behavior were tested
      by maintaining animals on either distilled water (N = 60) or water containing 1%
      calcium gluconate (N = 60) for 3 days. Animals that were maintained on high
      calcium drinking water presented increased serum calcium levels (control = 10.12
      +/- 0.46 vs calcium treated = 11.62 +/- 0.51 microg/dl). Increase of brain
      calcium levels was not statistically significant. In the behavioral experiments
      each rat was used for only one test. Rats that were maintained on high calcium
      drinking water showed increased open-field behavior of ambulation (20.68%) and
      rearing (64.57%). On the hole-board, calcium-supplemented animals showed
      increased head-dip (67%) and head-dipping (126%), suggesting increased ambulatory
      and exploratory behavior. The time of social interaction was normal in animals
      maintained on drinking water containing added calcium. Rats supplemented with
      calcium and submitted to elevated plus-maze tests showed a normal status of
      anxiety and elevated locomotor activity. We conclude that elevated levels of
      calcium enhance motor and exploratory behavior of rats without inducing other
      behavioral alterations. These data suggest the need for a more detailed analysis
      of several current proposals for the use of calcium therapy in humans, for
      example in altered blood pressure states, bone mineral metabolism disorders in
      the elderly, hypocalcemic states, and athletic activities.

PMID- 11960195
TI  - Polysiloxane/PVA-glutaraldehyde hybrid composite as solid phase for
      immunodetections by ELISA.
AB  - We developed an efficient method to prepare a hybrid inorganic-organic composite
      based on polyvinyl alcohol (PVA) and polysiloxane using the sol-gel disc
      technique. Antigen obtained from Yersinia pestis was covalently immobilized onto
      these discs with glutaraldehyde and used as solid phase in ELISA for antibody
      detection in serum of rabbits experimentally immunized with plague. Using 1.25
      microg antigen per disc, a peroxidase conjugate dilution of 1:4,000 and a serum
      dilution of 1:200 were adequate for the establishment of the procedure. These
      values are similar to those used for PVA-glutaraldehyde discs, plasticized filter
      paper discs and the polyaniline-Dacron composite discs. This procedure is
      comparable to that which utilizes the adsorption of the antigen to conventional
      PVC plates, with the amount of antigen being one fourth that employed in
      conventional PVC plates (5 microg/well). In addition to the performance of the
      polysiloxane/PVA-glutaraldehyde disc as a matrix for immunodetection, its easy
      synthesis and low cost are additional advantages for commercial application.

PMID- 11960196
TI  - Episodes of water deprivation enhance daily hypertonic NaCl intake in rats.
AB  - Water and 1.8% NaCl intake was recorded daily in adult male rats (N = 6)
      submitted to four water deprivations plus four sodium appetite tests, each at the
      end of each 7-day interval, or in controls (non-deprived, N = 6). Water
      deprivation was achieved by removing water and 1.8% NaCl for 24 h. Water was then
      offered for 2 h. At the end of this period, 1.8% NaCl was also offered in
      addition to water (sodium appetite test). Average daily 1.8% NaCl intake was
      enhanced from 5.2 +/- 1.0 to 15.7 +/- 2.5 ml from the first to the fifth week in
      the experimental group and was unchanged in the control group. Daily water intake
      was not altered in either group. Thus, repeated episodes of water deprivation
      enhance daily NaCl intake.

PMID- 11960197
TI  - Proconvulsant effects of high doses of venlafaxine in pentylenetetrazole
      convulsive rats.
AB  - Venlafaxine, an atypical antidepressant drug, has been used to treat several
      neurological disorders, presenting excellent efficacy and tolerability. Clinical
      seizures after venlafaxine treatment have occasionally been reported when the
      drug was used at very high doses or in combination with other medications. The
      aim of the present study was to investigate the convulsant effects of venlafaxine
      in rats under controlled laboratory conditions. Adult male Wistar rats (8 per
      group) receiving venlafaxine or saline at the doses of 25-150 mg/kg were
      subjected 30 min later to injections of pentylenetetrazole at the dose of 60
      mg/kg. The animals receiving 75, 100 and 150 mg/kg venlafaxine presented
      increased severity of convulsion when compared to controls (P = 0.02, P = 0.04,
      and P = 0.0004, respectively). Indeed, an increased percentage of death was
      observed in these groups (50, 38, and 88%, respectively) when compared to the
      percentage of death in the controls (0%). The group receiving 150 mg/kg showed an
      reduction in death latency (999 +/- 146 s) compared to controls (1800 +/- 0 s;
      cut-off time). Indeed, in this group, all animals developed seizures prior to
      pentylenetetrazole administration. Surprisingly, the groups receiving venlafaxine
      at the doses of 25 and 50 mg/kg showed a tendency towards an increase in the
      latency to the first convulsion. These findings suggest that venlafaxine at doses
      of 25 and 50 mg/kg has some tendency to an anticonvulsant effect in the rat,
      whereas doses of 75, 100 and 150 mg/kg presented clear proconvulsant effects in
      rats submitted to the pentylenetetrazole injection. These findings are the first
      report in the literature concerning the role of venlafaxine in seizure genesis in
      the rat under controlled conditions.

PMID- 11960198
TI  - Effect of acute treatment with a water-alcohol extract of Erythrina mulungu on
      anxiety-related responses in rats.
AB  - We investigated the effect of acute oral treatment with a water-alcohol extract
      of the inflorescence of Erythrina mulungu (EM, Leguminosae-Papilionaceae) (100,
      200 and 400 mg/kg) on rats submitted to different anxiety models: the elevated T
      maze (for inhibitory avoidance and escape measurements), the light/dark
      transition, and the cat odor test. These models were selected for their presumed
      capacity to demonstrate specific subtypes of anxiety disorders as recognized in
      clinical practice. Treatment with 200 mg/kg EM impaired avoidance latencies
      (avoidance 1 - 200 mg/kg EM: 18 +/- 7 s, control group: 40 +/- 9 s; avoidance 2 -
      200 mg/kg EM: 15 +/- 4 s, control group: 110.33 +/- 38 s) in a way similar to the
      reference drug diazepam (avoidance 1: 3 +/- 0.79 s; avoidance 2: 3 +/- 0.76 s),
      without altering escape. Additionally, the same treatments increased the number
      of transitions (200 mg/kg EM: 6.33 +/- 0.90, diazepam: 10 +/- 1.54, control
      group: 2.78 +/- 0.60) between the two compartments and the time spent in the
      lighted compartment in the light/dark transition model (200 mg/kg EM: 39 +/- 7 s;
      diazepam: 61 +/- 9 s; control group: 14 +/- 4 s). The dose of 400 mg/kg EM also
      increased this last measurement (38 +/- 8 s). These results were not due to motor
      alterations since no significant effects were detected in the number of crossings
      or rearings in the arena. Furthermore, neither EM nor diazepam altered the
      behavioral responses of rats to a cloth impregnated with cat odor. These
      observations suggest that EM exerts anxiolytic-like effects on a specific subset
      of defensive behaviors, particularly those that have been shown to be sensitive
      to low doses of benzodiazepines.

PMID- 11960199
TI  - Excitotoxic median raphe lesions aggravate working memory storage performance
      deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus
      in the inhibitory avoidance task in rats.
AB  - The interactions between the median raphe nucleus (MRN) serotonergic system and
      the septohippocampal muscarinic cholinergic system in the modulation of immediate
      working memory storage performance were investigated. Rats with sham or ibotenic
      acid lesions of the MRN were bilaterally implanted with cannulae in the dentate
      gyrus of the hippocampus and tested in a light/dark step-through inhibitory
      avoidance task in which response latency to enter the dark compartment
      immediately after the shock served as a measure of immediate working memory
      storage. MRN lesion per se did not alter response latency. Post-training
      intrahippocampal scopolamine infusion (2 and 4 microg/side) produced a more
      marked reduction in response latencies in the lesioned animals compared to the
      sham-lesioned rats. Results suggest that the immediate working memory storage
      performance is modulated by synergistic interactions between serotonergic
      projections of the MRN and the muscarinic cholinergic system of the hippocampus.

PMID- 11960200
TI  - Evaluation of the cholinomimetic actions of trimethylsulfonium, a compound
      present in the midgut gland of the sea hare Aplysia brasiliana (Gastropoda,
      Opisthobranchia).
AB  - Trimethylsulfonium, a compound present in the midgut gland of the sea hare
      Aplysia brasiliana, negatively modulates vagal response, indicating a probable
      ability to inhibit cholinergic responses. In the present study, the
      pharmacological profile of trimethylsulfonium was characterized on muscarinic and
      nicotinic acetylcholine receptors. In rat jejunum the contractile response
      induced by trimethylsulfonium (pD2 = 2.46 +/- 0.12 and maximal response = 2.14 +/
      0.32 g) was not antagonized competitively by atropine. The maximal response
      (Emax) to trimethylsulfonium was diminished in the presence of increasing doses
      of atropine (P<0.05), suggesting that trimethylsulfonium-induced contraction was
      not related to muscarinic stimulation, but might be caused by acetylcholine
      release due to presynaptic stimulation. Trimethylsulfonium displaced [3H]
      quinuclidinyl benzilate from rat cortex membranes with a low affinity (Ki = 0.5
      mM). Furthermore, it caused contraction of frog rectus abdominis muscles (pD2 =
      2.70 +/- 0.06 and Emax = 4.16 +/- 0.9 g), which was competitively antagonized by
      d-tubocurarine (1, 3 or 10 microM) with a pA2 of 5.79, suggesting a positive
      interaction with nicotinic receptors. In fact, trimethylsulfonium displaced [3H]
      nicotine from rat diaphragm muscle membranes with a Ki of 27.1 microM. These
      results suggest that trimethylsulfonium acts as an agonist on nicotinic
      receptors, and thus contracts frog skeletal rectus abdominis muscle and rat
      jejunum smooth muscle via stimulation of postjunctional and neuronal
      prejunctional nicotinic cholinoreceptors, respectively.

PMID- 11960201
TI  - Plasma and testicular testosterone levels, volume density and number of Leydig
      cells and spermatogenic efficiency of rabbits.
AB  - Plasma and tissue testosterone concentrations were determined by radioimmunoassay
      in 12 eight-month-old sexually mature New Zealand White rabbits and evaluated for
      possible associations with spermatogenic efficiency as well as with volume
      density and number of Leydig cells. Testicular tissue was processed
      histologically and histometry was performed in order to quantify germ cells,
      Sertoli cells and Leydig cells. Spermatogenic efficiency, reported as the ratios
      among germ cells (spermatogonia, primary spermatocytes and round spermatids) and
      by the ratio of germ cells to Sertoli cells, was not associated with testosterone
      levels. However, Leydig cell parameters such as number of Leydig cells per gram
      of testis, total number of Leydig cells per testis and percent cell volume of
      Leydig cell nuclei were correlated significantly with testosterone levels. The
      statistically significant correlation (r = 0.82, P<0.05) observed between
      testosterone levels and the number of Leydig cells per gram of testis suggests
      that, in the rabbit, the latter parameter can serve as a criterion for monitoring
      testosterone levels in this species under normal conditions.

PMID- 11960202
TI  - Diet and healthy bones.

PMID- 11960203
TI  - Glucorticoids and bone: some general remarks and some special observations in
      pediatric patients.

PMID- 11960204
TI  - The fetal origins of osteoporotic fracture.

PMID- 11960205
TI  - Rickets.

PMID- 11960206
TI  - Sir James Paget: the man and the eponym.

PMID- 11960207
TI  - The "muscle-bone unit" in children and adolescents.

PMID- 11960208
TI  - Detection of osteoporosis by dual energy X-ray absorptiometry (DXA) of the
      calcaneus: is the WHO criterion applicable?
AB  - The study assessed the precision, sensitivity, and specificity of a recently
      developed peripheral dual-energy X-ray absorptiometry (DXA) scanner, applied to
      the calcaneus, in the identification of individuals with osteoporosis at axial
      sites by DXA. Two hundred and two women, aged 55.2 +/- l3.7 years (mean +/- SD),
      participated in the study. The precisions (coefficient of variation) of
      measurements in vitro (0.48%) and in vivo (1.40%) were very good. The in vivo
      precision was independent of the operator, foot size, foot width, weight, height,
      and body mass index. Calcaneus BMD correlated moderately (r = 0.494-0.690, P
      <0.001) with axial BMD measurements by DXA. Using the World Health Organization
      (WHO) criterion for defining osteoporosis (T score ? -2.5) the specificity of the
      calcaneus to identify patients with osteoporosis at total hip, femoral neck,
      spine, or any of these axial sites was excellent (97.0%, 97.0%, 96.5%, and 97.1%,
      respectively); however, the sensitivity was poor (58.8%, 36.4%, 21.8%, and 20.3%,
      respectively). Therefore, the WHO criterion is not appropriate for DXA calcaneus.
      Based on femoral neck BMD for detection of osteoporosis, a more appropriate
      calcaneus T score threshold would be -1.4 by analyses of receiver-operator
      characteristic curves; this might serve to select those patients who might
      appropriately be referred for axial DXA.

PMID- 11960210
TI  - Deletion of chromosome 1, but not mutation of MEN-1, predicts prognosis in
      sporadic pancreatic endocrine tumors.
AB  - Pancreatic endocrine tumors (PETs) may be sporadic or inherited in the multiple
      endocrine neoplasia type 1 (MEN-1) syndrome. The inherited form is caused by
      mutations of the MEN-1 gene, which functions as a tumor suppressor gene and maps
      to chromosome 11q13. These tumors tend to have a better prognosis than their
      sporadic counterparts, which often have mutations of the MEN-1 gene. Previous
      molecular analyses of sporadic PETs suggest a high frequency of loss of
      heterozygosity (LOH) at chromosome 1 as well as mutation of MEN-1. In this study
      we correlate abnormalities of MEN-1 and chromosome 1 LOH with the biological
      behavior of sporadic PETs. Loss of heterozygosity for markers at chromosome 11q13
      and mutation of MEN-1 were equally frequent in tumors with or without liver
      metastases. Mutation of MEN-1 is more frequent in gastrinomas than in non
      gastrinomas. Loss of heterozygosity for markers on chromosome 1 is more frequent
      in PETs with liver metastases. These results suggest a molecular tumor model in
      which there is a dichotomy in the development of benign and malignant PETs.

PMID- 11960209
TI  - Inducible nitric oxide synthase: from cloning to therapeutic applications.
AB  - Elucidation of the many roles of nitric oxide (NO) in homeostasis and disease
      states has uncovered many areas where manipulation of NO production would be of
      therapeutic benefit. Recent advances in gene transfer technology and the cloning
      of the inducible nitric oxide synthase (iNOS) gene have led to the development of
      strategies for gene therapy to increase NO production for the treatment of
      disorders ranging from vascular restenosis to impaired wound healing. This review
      summarizes the current status of iNOS gene therapy research.

PMID- 11960211
TI  - Application of molecular biology studies to gene therapy treatment strategies.
AB  - The diagnosis of pancreatic cancer continues to produce fear in both patients and
      practitioners in large part owing to the likely incurability in all for whom the
      diagnosis is made. It is this reality that continually motivates the surgical and
      medical oncologists who endeavor to treat these patients. Currently, the cure
      rate for pancreatic cancer has improved only minimally, and the overall survival
      of patients remains dismal, with fewer than 5% of patients alive at 5 years and
      92% of these patients dead at 2 years. This current treatment status has
      stimulated numerous studies endeavoring to understand the diverse mechanisms of
      cell growth in this tumor. Intensive investigative efforts have produced the
      understanding of new tumor suppressor genes such as DPC4 and an increasing
      understanding of tyrosine kinase receptors and signal transduction and their
      regulation of programmed cell death (apoptosis). Detection of these numerous
      genetic defects may give new insights and understanding of the highly chemo- and
      radioresistant nature of pancreatic cancer. These same findings also provide the
      basis for the development of new potential therapies for pancreatic cancer
      through gene therapy. This paper reviews the significant molecular biologic
      findings and their influence on the development of gene therapy strategies in the
      treatment of pancreatic adenocarcinoma.

PMID- 11960212
TI  - Radical second resection provides survival benefit for patients with T2
      gallbladder carcinoma first discovered after laparoscopic cholecystectomy.
AB  - Port site recurrence or peritoneal seeding is a fatal complication following
      laparoscopic cholecystectomy for gallbladder carcinoma. The aims of this
      retrospective analysis were to determine the association of gallbladder
      perforation during laparoscopic cholecystectomy with port site/peritoneal
      recurrence and to determine the role of radical second resection in the
      management of gallbladder carcinoma first diagnosed after laparoscopic
      cholecystectomy. A total of 28 patients undergoing laparoscopic cholecystectomy
      for gallbladder carcinoma were analyzed, of whom 10 had a radical second
      resection. Five patients had recurrences; port site/peritoneum recurrence in 3
      and distant metastasis in 2. The incidence of port site/peritoneal recurrence was
      higher in patients with gallbladder perforation (3/7, 43%) than in those without
      (0/21, 0%) (p = 0.011). The outcome after laparoscopic cholecystectomy was worse
      in 7 patients with gallbladder perforation (cumulative 5-year survival of 43%)
      than in those without (cumulative 5-year survival of 100%) (p <0.001). Among 13
      patients with a pT2 tumor, the outcome after radical second resection (cumulative
      5-year survival of 100%) was better than that after laparoscopic cholecystectomy
      alone (cumulative 5-year survival of 50%) (p = 0.039), although there was no
      survival benefit of radical second resection in the 15 patients with a pT1 tumor
      (p = 0.65). In conclusion, gallbladder perforation during laparoscopic
      cholecystectomy is associated with port site/peritoneal recurrence and worse
      patient survival. Radical second resection may be beneficial for patients with
      pT2 gallbladder carcinoma first discovered after laparoscopic cholecystectomy.

PMID- 11960213
TI  - Intramuscular administration of very high dose of alpha-tocopherol protects liver
      from severe ischemia/reperfusion injury.
AB  - The effect of intramuscular administration of high (30 mg/kg body weight for 3
      days) or very high (300 mg/kg body weight for 3 days) doses of a-tocopherol to
      Wistar rats subjected to total severe warm hepatic ischemia and reperfusion was
      investigated. After a 60-minute period of total hepatic ischemia and 120 minutes
      of reperfusion, animals were killed, and liver samples were taken for
      determination of malondialdehyde (MDA) and histological examinations. Blood
      samples were also taken for assay of serum a-tocopherol, alanine transaminase
      (ALT), aspartate transaminase (AST), and lactic dehydrogenase (LDH). Additional
      animals were followed for a 7-day survival rate determination. Results showed
      that ischemia and reperfusion decreased the survival rate to 10%, whereas the
      levels of AST, ALT, and LDH in serum were increased compared with levels in
      animals that were sham operated. The MDA concentrations in liver were also
      increased, from 1.142 to 1.567 nmoles/g, whereas the levels of a-tocopherol in
      serum were decreased from 10.20 to 1.80 mmol/L. Pretreatment with a-tocopherol
      increased the viability to 50% and 70%, for the high and very high doses,
      respectively, and decreased the levels of AST, ALT, and LDH in serum. It also
      decreased the MDA concentrations in liver to 0.975 and 0.774 nmoles/g for the
      high and very high doses of a-tocopherol, respectively, whereas it increased the
      level of a-tocopherol in serum to 11.25 and 13.02 mmol/L for the high and very
      high doses, respectively. Histological examinations showed protection of the
      liver parenchyma in the animals treated with a-tocopherol.

PMID- 11960215
TI  - Endocrine gene neurotensin: molecular mechanisms and a model of intestinal
      differentiation.
AB  - The peptide neurotensin (NT) is an important intestinal hormone that affects
      gastrointestinal (GI) secretion, motility, and growth. This review describes the
      effects of NT in the GI tract and the distribution and localization of the gene
      encoding NT (i.e., NT/N). In addition, the molecular regulation of NT/N gene
      expression is discussed with special emphasis on the transcription factors,
      signal transduction pathways, and the role of gene methylation in modulating NT/N
      gene expression. Our studies have identified the NT/N gene as an excellent
      molecular model by which to define factors regulating intestinal cell
      differentiation. The in-depth analysis of the cellular processes leading to the
      expression of "model" intestinal genes, such as NT/N, can provide better
      understanding of normal gut development and function as well as defining more
      clearly the cellular events leading to gut neoplasia.

PMID- 11960216
TI  - Impact factors: facts and myths.

PMID- 11960217
TI  - Correlation of 3D MR coronary angiography with selective coronary angiography:
      feasibility of the motion-adapted gating technique.
AB  - The aim of this study was to verify the feasibility of a respiratory motion
      compensation technique (motion-adapted gating, MAG) for visualization of coronary
      arteries (CA) by correlation with selective coronary angiography (SCA). Fifteen
      subjects (11 patients, mean age 61.3 years, age range 41-73 years; and 4 healthy
      volunteers, mean age 32.3 years, age range 31-35 years) were investigated. A
      Philips Gyroscan ACS-NT was used, operating at 1.5 T, was combined with the
      PowerTrak 6000 gradient system. An ECG-triggered, respiratory motion-gated 3D
      turbo field echo sequence was used. The real-time algorithm utilized the concept
      of k-space weighting in combination with automatic analysis of respiratory
      motion. The main CA were investigated. Qualitative analysis was performed by
      three blinded investigators. Visibility was graded on a five-point scale (0=not
      visualized, 1=insufficient, 2=sufficient, 3=good, 4=excellent). Segments graded 2
      4 were defined as adequately visualized. Sixty-two of 88 assessable CA segments
      in patient, and 22 of 32 in volunteer group were adequately visualized.
      Visibility of CA was classified as excellent for proximal RCA (avg. 3.6+/-0.5),
      good for LM, proximal LAD, proximal LCX, middle RCA and sufficient for middle
      LAD. Sensitivity, specificity, positive and negative predictive values for
      coronary MRA in detection of CA stenoses with luminal narrowing >/=50% were 88,
      94, 83, and 96%, respectively. Magnetic resonance imaging in combination with MAG
      has proven to be a promising technique for noninvasive imaging of CA due to good
      image quality and a patient convenient free-breathing technique.

PMID- 11960218
TI  - Imaging of lymphadenopathy in the neck.
AB  - Imaging is playing a major role in the assessment of cervical lymphadenopathy. In
      infectious disease, the assessment of abscess formation and the relation of the
      abscess to surrounding vital structures is crucial for its management. In head
      and neck malignancies, imaging can be helpful for staging. Imaging of the neck
      for the assessment of nodal metastases can be used to detect occult metastases or
      to assess operability of palpable metastases. The detection of small occult
      metastases has limitations, as micrometastases cannot be depicted; however,
      imaging can fulfill a role in diminishing the risk of occult metastases, and thus
      influence management. For this purpose a very sensitive technique is necessary.
      The currently used radiological criteria are not sensitive enough to accomplish
      enough reduction of the risk of occult metastases; therefore, more sensitive CT
      and MRI criteria, but especially ultrasound-guided aspiration, should be employed
      to assess the clinically negative neck.

PMID- 11960219
TI  - CT findings in a case of laryngeal sarcoidosis.
AB  - Laryngeal sarcoidosis is a rare manifestation of systemic sarcoidosis. It affects
      mainly the supraglottic larynx. Involvement of the glottic and subglottic levels
      are exceptional. We present the case of a 56-year-old man with a 2-year history
      of systemic sarcoidosis, involving the mucosa of paranasal sinuses, a joint, and
      mediastinal lymph nodes, who developed laryngeal sarcoidosis. We emphasize the CT
      appearance of laryngeal sarcoidosis.

PMID- 11960220
TI  - Olfactory schwannoma.
AB  - Olfactory schwannomas are very rare. For this reason they have never been
      diagnosed preoperatively. We report a case and describe the CT and MR imaging
      findings. Clinically, the young age of presentation, and radiologically the
      presence of bone scalloping, and the absence of both bone sclerosis and a dural
      tail, may help in the differential diagnosis of meningioma.

PMID- 11960221
TI  - Multidetector helical CT of the liver for tumor detection and characterization.
AB  - Multidetector-row CT (MDCT) scanners have been recently introduced into clinical
      practice. Major attributes that are improved are the z-axis coverage speed and
      the longitudinal resolution. These improvements translate into rapid hepatic
      imaging and allow new imaging protocols. Thin sections can now be used on a
      routine basis in single-breath-hold technique. This results in improved lesion
      detection and the nearly isotropic image acquisition provides high-resolution
      multiplanar reformations. Furthermore, the ability to scan through the entire
      liver in 10 s or less allows acquisition of two separate sets of CT images of the
      liver within the time generally regarded as the hepatic arterial dominant phase
      in monoslice CT; thus, MDCT may demonstrate three clear separate distinct hepatic
      circulatory phases with a triple-pass technique. Multidetector-row CT with the
      improvements in morphological and functional information compared with single
      slice CT enables a comprehensive approach to hepatic imaging within a single
      examination.

PMID- 11960222
TI  - The multistep process of hepatocarcinogenesis in cirrhosis with imaging
      correlation.
AB  - Hepatocarcinogenesis in the cirrhotic liver has recently become a subject of
      intense investigation. The development of hepatocellular nodules demonstrating
      varying degrees of cellular and architectural atypia suggests that these nodular
      lesions represent a pathway of carcinogenesis in cirrhosis of different
      etiologies. This pathway involves processes, such as capillarization and
      neoangiogenesis, leading to a gradual change in blood supply from portal to
      arterial, as a dysplastic nodule becomes hepatocellular carcinoma. These changes
      in intranodular blood supply create different enhancement patterns in the two
      phases of liver circulation after an intravenous contrast injection on multi
      phase helical CT or dynamic gadolinium-enhanced MRI. This article reviews the
      current concepts regarding the vascular changes occurring in dysplastic nodules
      in the multistep process of hepatocarcinogenesis, along with the associated
      imaging manifestations. Some practical issues and dilemmas regarding the follow
      up and biopsy of these lesions are also discussed.

PMID- 11960223
TI  - Hemoretroperitoneum associated with liver bare area injuries: CT evaluation.
AB  - In hepatic injury restricted to the postero-superior region of segment VII (bare
      area), hemoperitoneum may be absent and this condition may be associated with
      hemoretroperitoneum. The aim of this paper is to present the association between
      bare area injuries and hemoretroperitoneum evaluated by CT. The CT examinations
      of 32 patients with blunt liver trauma were reviewed and the number and location
      of lesions were evaluated. Right lobe involvement was identified, focusing on the
      bare area lesions. The presence of hemoperitoneum and hemoretroperitoneum were
      determined. In the 32 patients 44 parenchymal lesions were detected. Segment VII
      was involved in 16 cases: 5 patients presented an intraparenchymal lesion, 11
      patients a lesion emerging to the liver surface. In 8 cases the lesion was
      localized in the bare area. In the 16 patients presenting a segment-VII lesion,
      hemoperitoneum was detected in 3 cases, hemoretroperitoneum in 4 cases, and both
      conditions in 4 cases. A traumatic hepatic lesion may be associated with
      hemoretroperitoneum rather than hemoperitoneum. This justifies the absence of
      clinical signals of peritoneal irritation; the negativity of both US scan and
      peritoneal lavage may cause an inappropriate therapeutic management. Computed
      tomography yields both the detection of the parenchymal damage and the correct
      localization of the intraperitoneal and retroperitoneal hemorrhage.

PMID- 11960224
TI  - Fat containing unusual tumor of the pancreas.
AB  - Fat-containing pancreatic tumors are very rare. In the literature, less than ten
      cases of lipoma originating from the pancreas have been reported. We present a
      case of pancreatic lipoma in a 65-year-old woman with findings of
      ultrasonography, computed tomography, and magnetic resonance imaging in addition
      to a brief review of the literature.

PMID- 11960225
TI  - Pancreatic involvement in primary amyloidosis: radiologic findings.
AB  - Amyloidosis is a rare disease that can involve a great variety of organs. As a
      consequence, clinical and radiological manifestations are very different as well.
      We report on a patient with primary amyloidosis who presented with diffuse
      pancreatic involvement detected by ultrasound, helical CT, and MRI. There are
      very few imaging descriptions about this glandular involvement in amyloidosis in
      the literature. Despite the apparent uncommon radiological appearance, we believe
      that this entity should be taken into account in the differential diagnosis of
      diffuse infiltrative pancreatic lesions in the appropriate clinical and
      analytical setting.

PMID- 11960226
TI  - Imaging of the posterior pelvic floor.
AB  - Disorders of the posterior pelvic floor are relatively common. The role of
      imaging in this field is increasing, especially in constipation, prolapse and
      anal incontinence, and currently imaging is an integral part of the investigation
      of these pelvic floor disorders. Evacuation proctography provides both structural
      and functional information for rectal voiding and prolapse. Dynamic MRI may be a
      valuable alternative as the pelvic floor muscles are visualised, and it is
      currently under evaluation. Endoluminal imaging is important in the management of
      anal incontinence. Both endosonography and endoanal MRI can be used for detection
      of anal sphincter defects. Endoanal MRI has the advantage of simultaneously
      evaluating external sphincter atrophy, which is an important predictive factor
      for the outcome of sphincter repair. Many aspects of constipation and prolapse
      remain incompletely understood and treatment is partly empirical; however,
      imaging has a central role in management to place patients into treatment-defined
      groups.

PMID- 11960227
TI  - Swallowing abnormalities in multiple sclerosis: correlation between
      videofluoroscopy and subjective symptoms.
AB  - The purpose of this study was to evaluate if subjective symptoms indicating an
      impaired deglutition correlate with videofluoroscopic findings in patients with
      multiple sclerosis (MS). Videofluoroscopic examinations of 18 MS patients were
      analyzed by a radiologist and a logopedist and compared with the symptoms of
      these patients. Four patients complained about permanent dysphagia. Six patients
      reported mild and intermittent difficulties in swallowing, but were asymptomatic
      at the time of videofluoroscopy. Eight patients had no symptoms regarding their
      deglutition. All patients ( n=4) who complained of permanent dysphagia showed
      aspiration. All patients ( n=6) with mild and intermittent difficulties in
      swallowing showed undercoating of the epiglottis and/or laryngeal penetration. Of
      those 8 patients without any swallowing symptoms, only 2 had a normal
      videofluoroscopy. Swallowing abnormalities seem to be much more frequent in
      patients with MS than generally believed and they may easily be missed clinically
      as long as the patients do not aspirate.

PMID- 11960228
TI  - Mesenteric lipoma: report of a case with emphasis on US findings.
AB  - Mesenteric lipoma (ML) is a relatively rare disease that has been very
      infrequently reported. We present the clinical data and medical imaging results
      of an asymptomatic case with ML incidentally detected by sonography (US). On US
      the lesion was imaged as a well-demarcated hypoechoic mass with multiple linear
      echoes. The mass also changed location under probe compression. The lesion was
      imaged as a clearly demarcated non-enhanced homogeneous fat-density mass on CT.
      Color Doppler US and angiography confirmed the avascular nature of the mass.
      Knowledge of the US findings in this case is useful for the diagnosis of ML.

PMID- 11960229
TI  - Duplex ultrasonographic study of the renal arteries before and after renal artery
      stenting.
AB  - The aim of our study was to evaluate feasibility and accuracy of colour-coded
      duplex US in the detection of renal artery stenosis before and after stenting.
      Eighty-four patients (23 women, 61 men; mean age 64 years) with significant renal
      artery stenosis were studied with Doppler US, before and after stenting. A
      combined anterior and translumbar approach was used to visualise the renal
      arteries. Renal artery stenosis and in-stent restenosis were proved by the
      increase of renal peak systolic velocity (PSV) and reno-aortic ratio (RAR).
      Laboratory-specific threshold values of PSV and RAR were used to assess
      sensitivity and specificity of Doppler US. The renal arteries were visualised in
      all patients (feasibility 100%). A statistically significant difference of PSV
      and RAR was demonstrated between patent and stenotic renal arteries, before
      stenting, and between stenotic and stented renal arteries. No difference was
      demonstrated in cases of in-stent restenosis ( n=21). Before stenting,
      sensitivity of PSV and RAR was 93%, whereas specificity rates were 92 and 96%,
      respectively. After stenting sensitivity and specificity rates were,
      respectively, 90 and 93% for PSV, and 95 and 95% for RAR. Doppler US represents a
      feasible and reliable technique in the detection of renal artery stenosis and in
      stent restenosis, although laboratory-specific threshold values are required to
      improve its accuracy.

PMID- 11960230
TI  - Angiography for renal artery stenosis: no additional impairment of renal function
      by angioplasty.
AB  - The aim of this study was to compare renal function between patients with renal
      angiography and patients with renal angiography and angioplasty (AP) for renal
      artery stenosis (RAS). Forty-seven patients with suspected RAS were prospectively
      investigated by digital subtraction angiography (DSA) using non-ionic low osmolar
      contrast media (CM). In 22 patients RAS was detected and in 16 cases an
      angioplasty was performed in the same session. The following parameters were
      determined 1 day prior to and after the DSA, respectively: serum creatinine (S
      Crea, micromol/l) and single-shot inulin clearance (In-Cl, ml/min) for the
      evaluation of renal function; and urine alpha 1-microglobuline (AMG, microg/g
      Crea) and beta-N-acetyl-glucoseaminidase (beta-NAG, U/g Crea) as markers of
      tubular toxicity. Serum creatinine was measured additionally 2 days after CM had
      been injected. In both groups with and without AP 174+/-65 and 104+/-56 ml of CM
      ( p<0.0005) were used, respectively. There were no differences with regard to
      renal function or risk factors for CM nephrotoxicity between both groups. In the
      group with AP S-Crea and In-Cl (each: mean+/-SD) did not change significantly
      (before DSA: 171+/-158 and 61+/-24, after DSA: 189+/-177 and 61+/-25,
      respectively), beta-NAG (median) rose from 4 to 14 ( p<0.05) and AMG from 8 to 55
      (n.s., because of high SD). In the group without AP S-Crea increased from 134+/
      109 to 141+/-113 ( p<0.01), In-Cl dropped from 65+/-26 to 62+/-26 ( p<0,01), beta
      NAG (median) rose from 4 to 8 ( p=0.01), and AMG from 7 to 10 (n.s.). A rise in
      baseline S-Crea by more than 25% or 44 micromol/l occurred in 4 and 2 patients in
      the group with and without AP, respectively. Creatinine increase was reversible
      in all cases within 7 days. In this study using sensitive methods to detect
      changes of renal function and tubular toxicity no additional renal function
      impairment in DSA with angioplasty for RAS compared with DSA alone could be
      demonstrated. Our data suggest that AP performed for RAS has a beneficial effect
      on renal function.

PMID- 11960231
TI  - Replacement lipomatosis related to renal tuberculosis: imaging findings in one
      case.
AB  - Replacement lipomatosis of the kidney in a case of long-standing renal
      tuberculosis is reported. The radiologic and pathologic findings are described
      and the differential diagnosis is discussed. A hypothesis is given to explain the
      association of renal tuberculosis and replacement lipomatosis of the kidney.

PMID- 11960232
TI  - MR microscopy of hyaline cartilage: current status.
AB  - Cartilage degenerative diseases, such as osteoarthritis, affect million of
      people. Magnetic resonance imaging is presently the most accurate imaging
      modality in evaluating the state of hyaline cartilage; however, clinical MRI does
      not accurately reveal early degenerative alterations in cartilage, due mainly to
      low spatial resolution. Magnetic resonance microscopy (MRM, or microMRI) appears
      exceptionally well suited to the in vitro or ex vivo study of this heterogeneous
      tissue, due to its high spatial resolution; however, despite this, further
      studies are necessary to evaluate the potential of MRM in the detection of early
      cartilage damage. Herein we briefly review the current applications of MRM in the
      study of hyaline cartilage. In particular, we review the MR appearance of hyaline
      cartilage on high-resolution images, the different MRM techniques used to image
      normal and enzymatically or chemically degraded cartilage and the potential use
      of contrast agents. The future directions and the relevance of MRM findings for a
      better understanding of cartilage physiology in health and disease are also
      discussed.

PMID- 11960233
TI  - MR imaging of the anterior intermeniscal ligament: classification according to
      insertion sites.
AB  - Our objective was to study the frequency of anterior intermeniscal ligament on MR
      imaging and to make a classification according to its insertion sites on MR
      images. Sagittal T1-weighted and thin-section transverse T2*-weighted MR images
      of the knee were prospectively evaluated in 229 subjects without significant
      synovial effusion or total rupture of the anterior cruciate ligament. By using
      thin-section transverse images, the ligament was classified into three types
      according to its insertion sites (type A: between anterior horns of medial and
      lateral menisci; type B: between anterior horn of medial meniscus and anterior
      margin of lateral meniscus; type C: between anterior margins of medial and
      lateral menisci). On sagittal images location of the ligament was determined with
      respect to a line drawn between anterior of the tibial epiphysis and posterior of
      the intercondylar notch to look for a relation between its type on transverse
      images and location on sagittal images. Separately, arthroscopy was made in 36
      patients to verify the MR assessment of the presence of the ligament. Anterior
      intermeniscal ligament was found in 53% of the subjects. Type B was the most
      common group (58%). Magnetic resonance imaging has a sensitivity and a
      specificity of 67 and 100%, respectively, in the detection of the ligament. Types
      A and C had a statistically significant location posterior and anterior,
      respectively, to the master line on sagittal images. In arthroscopy, the ligament
      was either cord-like (67%) or flat (33%) in appearance. Routine sagittal MR
      images can help identify anterior intermeniscal ligament.

PMID- 11960234
TI  - MRI-guided trephine biopsy and fine-needle aspiration in the diagnosis of bone
      lesions in low-field (0.23 T) MRI system using optical instrument tracking.
AB  - The purpose of this study was to evaluate the feasibility of MRI-guided bone
      biopsy with optical instrument tracking and evaluate advantage of combined fine
      needle aspiration (FNA) with trephine biopsy. Twenty trephine bone biopsies and
      13 FNAs were performed under MRI and CT guidance in 14 patients. Informed consent
      was obtained from all patients. The evaluation of diagnostic accuracy was
      achieved by comparing the histopathological and cytological diagnosis with
      current or final diagnosis made during 6-month clinical follow-up. A 0.23-T open
      MRI scanner with interventional tools (Outlook Proview, Marconi Medical Systems,
      Cleveland, Ohio) was used. A surface coil was used. For trephine biopsy MRI
      compatible bone biopsy set (Daum medical, Schwerin, Germany) was used. The FNA
      was performed with MRI compatible 20-G needle (Cook, Bloomington, Ind.). The
      diagnostic accuracy of MRI-guided trephine biopsy was 95%. The FNA sample
      diagnosis concurred with the histological in 54%. Our results show that MRI
      guidance in bone biopsies is accurate and safe. It is comparable to CT-guided or
      open biopsy. The role of combined FNA with bone biopsies remains controversial.

PMID- 11960235
TI  - Hemophilic arthropathy. A scoring system for magnetic resonance imaging.
AB  - The aim of this study was to define a system for scoring hemophilic arthropathy
      (HA) based on MR findings, providing for objective evaluation of the degree of
      joint involvement and evolution after on-demand administration of FVIII
      substitutional therapy or prophylactic treatment. A total of 133 MR examinations
      (89 basal and 44 during follow-up) were performed in 25 patients. Patients were
      divided in two groups depending on the therapy received and the length of time
      that the disease had been evolving at the start of the study. Group I was
      composed of 10 patients with secondary prophylaxis and group II was composed by
      15 treated on demand. T1-weighted and T2*-weighted images performed on a 0.5-T
      unit were prospectively evaluated. The joint involvement was established on a
      scale of 0 (no abnormalities), I (minimal amount of hemosiderin), II (large
      amount of hemosiderin and isolated cartilaginous erosion), III (cartilage
      destruction, bone erosions, and subchondral cysts) to IV (large internal joint
      derangement, secondary osteoarthritis and/or ankylosis). At basal MR examination,
      patients of group I showed no abnormalities ( n=28, 75.6%), grade I ( n=3), and
      grade II ( n=6) of HA. Patients of group II corresponded to MR grades III ( n=21)
      and IV ( n=11) of HA. The MR follow-up showed improvement in three joints of
      group I and worsening in 5 joints in group I and 2 joints in group II. Early
      signs of HA were detected in 10 joints with MR imaging but were underestimated on
      plain radiographs. Advanced degrees of HA were classified as severe under both
      imaging techniques. Magnetic resonance is the preferred imaging technique to
      assess HA. The earliest signs of joint damage, detected by MR, are overlooked by
      plain radiography. The MR scoring system can be used for evaluating HA. Follow-up
      MR should be performed to evaluate regression or worsening of the abnormalities,
      primarily in the case of patients with prophylaxis who usually suffer normal or
      early joint involvement not detected by other means.

PMID- 11960236
TI  - Radiation-induced osteochondroma of the T4 vertebra causing spinal cord
      compression.
AB  - A case of a radiation-induced osteochondroma arising from the vertebral body of
      T4 in an 18-year-old man is reported. The patient presented with a history of
      progressive left lower extremity weakness. At 7 years of age, he had undergone
      resection of a cerebellar medulloblastoma and received adjunctive craniospinal
      irradiation and systemic chemotherapy. Both CT and MR imaging revealed an
      extradural mass contiguous with the posteroinferior endplate of the T4 vertebral
      body. This case indicates that radiation-induced osteochondroma should be
      considered in the differential diagnosis of patients with symptoms of myelopathy
      or nerve root compression and a history of radiation therapy involving the spine
      in childhood.

PMID- 11960237
TI  - Cranial imaging in child abuse.
AB  - Serious head injury in children less than 2 years old is often the result of
      child abuse. The role of the different neuroimaging modalities in child abuse is
      reviewed. Skull X-ray and cranial CT are mandatory. Repeat or serial imaging may
      be necessary and brain MR imaging may contribute to the diagnostic work-up,
      particularly in the absence of characteristic CT findings. The radiologist plays
      an important role in accurately identifying non-accidental cranial trauma. The
      clinical presentation can be non-specific or misleading. The possibility should
      be considered of a combined mechanism, i.e., an underlying condition with
      superimposed trauma. In this context, the radiologist is in the front line to
      suggest the possibility of child abuse. It is therefore important to know the
      spectrum of, sometimes subtle, imaging findings one may encounter.
      Ophthalmological examination is of the greatest importance and is discussed here,
      because the combination of retinal hemorrhages and subdural hematoma is very
      suggestive of non-accidental cranial trauma.

PMID- 11960239
TI  - Solitary hepatic infantile hemangioendothelioma: dynamic gadolinium-enhanced MR
      imaging findings.
AB  - We report the MRI findings of a solitary hepatic infantile hemangioendothelioma
      (IHE) diagnosed in a 14-day-old girl. To the best of our knowledge, only one
      report has illustrated the dynamic gadolinium-enhanced MR imaging features of IHE
      previously. Compounding the rarity of presentation as a solitary mass, the
      gadolinium-enhanced MRI appearance in our case is unique, because the IHE showed
      an early rim-like pseudocapsular enhancement followed by progressive fill-in of
      the lesion on delayed imaging.

PMID- 11960238
TI  - Proton magnetic resonance spectroscopy of the brain of a neonate with nonketotic
      hyperglycinemia: in vivo-in vitro (ex vivo) correlation.
AB  - Nonketotic hyperglycinemia (NKH) is an inborn error of amino acid metabolism
      caused by a defect in the glycine cleavage multienzyme complex resulting in high
      concentrations of glycine within the brain and spinal cord. Quantitative magnetic
      resonance spectroscopy ((1)H-MRS) allows measurement of absolute glycine
      concentrations within different parts of the brain in vivo. In addition, (1)H-MRS
      may be useful in monitoring treatment of NKH and to differentiate this disease
      from other disorders of glycine metabolism.

PMID- 11960241
TI  - Similarities and differences of MR findings between Japanese encephalitis and
      Wilson's disease.
AB  - Although Japanese Encephalitis (JE) and Wilson's disease (WD) are different
      entities, MR findings in both these conditions are quite similar. The purpose of
      this retrospective study was to find out the similarities and differences between
      JE and WD on MR imaging. The study group comprised 25 proven cases of JE and 10
      cases of WD. Spin echo (SE) TI- and T2-weighted imaging was performed on a 1.5-T
      MR system. Fourteen of these 35 cases (10 JE, 4 WD) were also examined using T1
      weighted magnetization transfer (MT) SE sequence before and after contrast
      administration. Although both JE and WD showed similar topographical distribution
      of lesions, predominant involvement of the basal ganglia and thalami, there were
      some differences. Brain stem lesion was more frequent for WD than for JE, and
      posteromedial part of the thalami was spared in WD. The lesion characteristics
      were also different between both; in WD mixed intensity in the basal ganglia and
      hyperintense linear rim at the peripheral putamen was observed frequently,
      whereas hyperintense basal ganglia on T2-weighted images, subacute hemorrhage in
      the thalami and meningeal enhancement were seen only in the patients with JE.
      These characteristic lesion criteria may help in differentiation of JE from WD on
      MR imaging.

PMID- 11960240
TI  - Growing Region Segmentation Software (GRES) for quantitative magnetic resonance
      imaging of multiple sclerosis: intra- and inter-observer agreement variability: a
      comparison with manual contouring method.
AB  - Lesion area measurement in multiple sclerosis (MS) is one of the key points in
      evaluating the natural history and in monitoring the efficacy of treatments. This
      study was performed to check the intra- and inter-observer agreement variability
      of a locally developed Growing Region Segmentation Software (GRES), comparing
      them to those obtained using manual contouring (MC). From routine 1.5-T MRI study
      of clinically definite multiple sclerosis patients, 36 lesions seen on proton
      density-weighted images (PDWI) and 36 enhancing lesion on Gd-DTPA-BMA-enhanced T1
      weighted images (Gd-T1WI) were randomly chosen and were evaluated by three
      observers. The mean range of lesion size was 9.9-536.0 mm(2) on PDWI and 3.6-57.2
      mm(2) on Gd-T1WI. The median intra- and inter-observer agreement were,
      respectively, 97.1 and 90.0% using GRES on PDWI, 81.0 and 70.0% using MC on PDWI,
      88.8 and 80.0% using GRES on Gd-T1WI, and 85.8 and 70.0% using MC on Gd-T1WI. The
      intra- and inter-observer agreements were significantly greater for GRES compared
      with MC ( P<0.0001 and P=0.0023, respectively) for PDWI, while no difference was
      found between GRES an MC for Gd-T1WI. The intra-observer variability for GRES was
      significantly lower on both PDWI ( P=0.0001) and Gd-T1WI ( P=0.0067), whereas for
      MC the same result was found only for PDWI ( P=0.0147). These data indicate that
      GRES reduces both the intra- and the inter-observer variability in assessing the
      area of MS lesions on PDWI and may prove useful in multicentre studies.

PMID- 11960242
TI  - Thoracic spinal intradural arachnoid cyst: report of two cases and review of
      literature.
AB  - We report two cases of spinal intradural arachnoid cyst at the thoracic level,
      presenting with long-standing symptoms of spinal cord compression and MRI
      findings that were overlooked for sometime initially. Because of the rarity of
      this disease, and because of the subtle changes on MRI, there was a definite
      delay in the diagnosis. In this report we emphasize the value of MRI and CT
      myelography in this disorder, and the need for them to be strongly correlated
      with the progression of the clinical picture.

PMID- 11960243
TI  - Preoperative and early postoperative magnetic resonance imaging in two cases of
      childhood choroid plexus carcinoma.
AB  - We present and illustrate the MRI appearances of two children with choroid plexus
      carcinoma. The MRI characteristics of these rare tumours are reviewed. Since
      total surgical resection is a significant prognostic factor, early postoperative
      MRI was performed in both cases to ensure surgical clearance. In one case a
      complete resection was documented and this patient remains well at short-term
      follow-up. Residual tumour was noted in the second case, but despite "second
      look" surgery there was subsequent local relapse.

PMID- 11960244
TI  - MR imaging of the vessel wall.
AB  - Since the risks for thrombosis are more dependent on plaque composition than on
      the degree of luminal narrowing, the radiological assessment of atherosclerosis
      should extend beyond mere depiction of the arterial lumen. High-resolution MRI of
      the vessel wall can provide important information about the individual makeup of
      atherosclerotic plaques, potentially enabling early detection and
      characterization of lesions before narrowing of the vessel lumen occurs. The MR
      based assessment of the vessel wall with sufficient spatial resolution and image
      contrast, however, remains challenging. Requirements include high signal-to-noise
      ratio, high contrast-to-noise ratio, good signal penetration depth and
      homogeneous signal throughout the vessel under investigation, as well as imaging
      protocols encompassing various contrast weightings. Numerous dedicated
      radiofrequency (RF) coils have been developed to achieve these goals employing
      either external surface phased-array coils, or alternatively, utilizing
      intravascular coils to image the vessel wall from inside the vessel and thus
      being invasive. For the non-invasive approach of imaging with surface coils, the
      carotid and the right coronary arteries have been favoured since they are of
      critical importance and since they are relatively superficial structures,
      accessible from the outside. To detect the early development of plaque and
      visualize it globally rather than locally, intravascular contrast agents on the
      basis of ultrasmall particles of iron oxide can be used as a marker of macrophage
      activity within the plaque. In the long run, it appears likely that the
      combination of luminal MR angiography with the administration of susceptibility
      based contrast agents and subsequent high-resolution MR of detected
      atherosclerotic lesions with dedicated RF coils could evolve as the diagnostic
      concept of choice for the assessment of atherosclerotic disease.

PMID- 11960245
TI  - Life-threatening vascular complications after central venous catheter placement.
AB  - The purpose of this retrospective study was to report 11 cases of severe vascular
      complications after central venous catheter misplacement. For each patient, data
      collection included body mass index, the diagnosis at admission, the site of the
      procedure, the type of catheter, coagulation parameters, the imaging modalities
      performed and the applied treatment. Eight patients had a lesion of the
      subclavian artery. Brachiocephalic vein perforations were assessed in three more
      patients. All patients had a chest roentgenogram after the procedure, six a CT
      examination, and four an angiographic procedure. Seven patients had a body mass
      index above 30, and 5 patients had coagulation disorders prior to the procedure.
      Seven patients were conservatively managed, 2 patients died despite
      resuscitation, 1 patient was treated with a stent graft, and one by
      superselective embolization. Subclavian or jugular vein temporary catheter
      positioning is a practical approach. Identification of any iatrogenic perforation
      of the subclavian artery or central veins urges obtaining a chest roentgenogram
      and, when required, a chest CT, selective angiograms or venograms. Body mass
      index superior to 30, previous unsuccessful catheterization attempts, and
      coagulation factor depletion seemed to account for risk factors. Recognition of
      clinical and radiological complications is mandatory.

PMID- 11960246
TI  - Subclavian artery angioplasty for the treatment of angina using a double balloon
      technique to protect a left internal mammary artery graft.
AB  - Percutaneous transluminal angioplasty (PTA) has proven to be a safe and effective
      method of treating subclavian stenosis with technical success rates ranging from
      83 to 100%. This technique, however, can result in distal embolisation. In the
      presence of a previous internal mammary bypass graft this may prove catastrophic,
      especially when that graft provides the dominant supply to the heart. Clearly any
      technique of reducing the risk of graft embolisation is valuable in this small
      subgroup of patients. The deployment of a double balloon to protect the left
      internal mammary artery graft to prevent this potentially fatal event has not
      been described previously.

PMID- 11960247
TI  - Bilateral transpopliteal approach for treatment of complex SFA and iliac
      occlusions.
AB  - We present a successful case of percutaneous intentional extraluminal
      recanalization (PIER) of bilateral long superficial femoral artery (SFA)
      occlusions and a long iliac artery occlusion through ultrasound-guided retrograde
      popliteal artery punctures. To our knowledge, PIER of SFA occlusions via
      popliteal approach has been reported in only three cases, and subintimal
      recanalization of combined SFA and iliac occlusions has not been reported.

PMID- 11960248
TI  - Aneurysms of saphenous vein grafts as late complication of coronary artery bypass
      surgery: successful exclusion by percutaneous transcatheter embolization.
AB  - We report a case of a 71-year-old man with a long coronary artery disease history
      and two sets of coronary artery bypass grafts. He developed large aortocoronary
      saphenous vein graft aneurysms in the two grafts from the first set of
      aortocoronary saphenous venous 20 years later. During the previous 3 years, the
      aneurysms grew in diameter from 22 to 50 mm. Because of severe renal
      insufficiency, and in order to avoid jeopardizing the late normal coronary artery
      bypass grafts by further thoracic surgery, we excluded successfully these altered
      grafts percutaneously by using 13 coils during the same procedure.

PMID- 11960249
TI  - Introduction to the DICOM standard.
AB  - Digital Imaging and Communication in Medicine (DICOM) has become one of the most
      popular standards in medicine. In the beginning, DICOM was used for communication
      of image data between different systems. Actual developments of the
      standardisation enables increasingly more DICOM-based services for the
      integration of modalities and information systems (e.g. RIS, PACS). In this
      article a review of the historical background, the technological concept, the
      organizational structure and current developments is given.

PMID- 11960250
TI  - Structural changes induced by antineoplastic therapies: keys to evaluate tumor
      response to treatment.
AB  - The criteria to define therapeutic response in oncology are those proposed by
      Miller, characterized by four response categories (complete response, partial
      response, no change, progression of disease), and based upon both measurable and
      non-measurable (and otherwise assessable) morphological parameters in comparison
      with baseline and subsequently modified following the Response Evaluation
      Criteria In Solid Tumors. In addition to these classical morphological criteria,
      we review the predictive value of structural changes in the evaluation of
      response to antineoplastic therapies. The goal of the present review is to
      evaluate in detail structural variations (calcification, fibrosis,
      differentiation, necrosis, cavitation, vascularization, edema, and pseudocapsule
      formation) induced by therapy, and to ascertain their significance in terms of
      biological evolution of the neoplastic process.

PMID- 11960251
TI  - Side markings of the neonatal chest X-ray: two legal cases of pneumothorax side
      mix up.
AB  - Two medicolegal case reports are presented. They involve chest X-ray with left
      and-right side confusion due to lack of radio-opaque side markers. Two premature
      babies with pneumothorax got thoracostomy on the wrong side, in one case with a
      fatal outcome.

PMID- 11960252
TI  - Pneumatosis intestinalis in the first weeks of life.

PMID- 11960253
TI  - Potentially misleading CT findings in fatty liver cirrhosis.

PMID- 11960254
TI  - Adventitial cystic disease of the popliteal artery: role of MRA.

PMID- 11960255
TI  - Differential diagnosis of asymptomatic retroperitoneal cystic lesion: a new case
      of retroperitoneal bronchogenic cyst.

PMID- 11960263
TI  - Assessing minimal residual disease (MRD) in leukemia: a changing definition and
      concept?
AB  - The term minimal residual disease (MRD) in its currently accepted application
      refers to low-level disease detected in a whole variety of clinical situations.
      It is used to describe residual disease after suboptimal induction chemotherapy,
      but at the same time refers to the lowest levels of disease potentially
      compatible with cure or to molecularly defined relapse after long-term remission.
      This discussion intends to redefine MRD into some biologically relevant
      subcategories which may warrant their own independent terminology.

PMID- 11960264
TI  - High-dose carboplatin and regimen-related toxicity following autologous bone
      marrow transplant.
AB  - Pharmacokinetic analysis of carboplatin dosing suggests a more accurate
      prediction of toxicity when the dose is based on the area under the plasma
      concentration vs time curve (AUC) instead of body surface area (BSA). We
      retrospectively calculated the carboplatin AUC of 117 patients who received an
      autologous stem cell transplant following a conditioning regimen consisting of
      carboplatin 1800 mg/m(2) and cyclophosphamide 6000 mg/m(2) to identify whether
      higher carboplatin exposure resulted in an increase in regimen-related non
      hematologic toxicities. The most common non-hematologic toxicities were
      gastrointestinal and hepatic. Twenty (17%) patients experienced additional > or
      =grade 2 toxicity, specifically, renal toxicity significantly associated with a
      higher median AUC of 10.2 mg/ml(-1) min (P = 0.001). Prior platinum therapy was
      also significantly associated with toxicity (P = 0.052). While carboplatin dose
      based on BSA varied minimally (median 990 (range 450-1340) mg, the calculated AUC
      showed a near four-fold range of exposure (median 7.8 (range 3.6 to 13.8) mg/ml(
      1) min). These data suggest a relationship between non-hematologic adverse events
      and the estimated AUC. Prospective trials will be necessary to identify the
      target carboplatin AUC which optimizes outcome and minimizes toxicity in the
      autologous transplant setting.

PMID- 11960265
TI  - Efficacy of an early intensification treatment integrating chemotherapy,
      autologous stem cell transplantation and radiotherapy for poor risk primary
      mediastinal large B cell lymphoma with sclerosis.
AB  - The aim of our study was to evaluate the impact of an early intensification
      programme including chemotherapy (CHT), autologous stem cell transplantation
      (ASCT) and radiation therapy (RT) in patients with primary mediastinal large B
      cell lymphoma (MLCL) with sclerosis presenting with adverse prognostic factors.
      Between 1993 and 1999, 19 patients with MLCL were referred to our institution.
      Four patients were classified as low risk according to the age-adjusted
      International Prognostic Index (AA-IPI). Fifteen (79%) were categorised in the
      high-intermediate or high risk group and were considered eligible for ASCT.
      Induction therapy consisted of VACOP-B (etoposide, doxorubicin, cyclophosphamide,
      vincristine, prednisone and bleomycin) for 12 weeks. After induction therapy the
      four low risk patients achieved a complete remission (CR) and did not undergo
      ASCT. Of the 15 poor risk patients, five achieved CR, seven partial remission
      (PR), and three showed refractory disease (RD). All these patients received
      mobilising therapy consisting of high-dose cyclophosphamide. After peripheral
      stem cell (PSC) collection, to obtain a greater tumor mass reduction before
      transplantation, the seven patients in PR underwent further treatment with high
      dose etoposide and those with RD received two cycles of DHAP (dexamethasone,
      cytarabine and cisplatin). At the time of ASCT, seven patients were in CR, six in
      PR and two had RD. After transplantation using BEAM as preparative regimen, all
      patients but one achieved a CR. Seven patients with minimal (<25%) residual mass
      at computed tomography scan received further mediastinal RT even if they had a
      negative Ga(67) scan. At a median follow-up of 35 months from transplantation the
      disease free survival is 93%. The outcome following this programme of early
      intensification in poor prognosis MLCL results in a high incidence of durable
      remissions even in patients with refractory disease.

PMID- 11960267
TI  - Arylsulfatase-A in umbilical cord blood: gestational age and mode of delivery do
      not influence enzyme activity.
AB  - The possibility of using umbilical cord blood for transplantation in several
      enzyme deficiencies has received increasing attention because of the availability
      of cord blood, the reduced incidence of post-transplantation complications, such
      as graft-versus-host disease and the possible accomplishment of good corrective
      results following transplantation, even in cases of greater HLA disparity. The
      use of hematopoietic stem cells from unrelated donors is even more highly
      recommended for the treatment of inherited enzyme deficiencies, because it might
      reduce the risk of the transplanted cells originating from a carrier of the
      defect, which might have an inadequate corrective ability. Our study was designed
      to elucidate whether the gestational age and mode of delivery influences the
      arylsulfatase-A activity in the umbilical cord blood. Enzyme activities proved to
      be similar in the four populations studied (full-term normal spontaneous vaginal
      delivery, full-term caesarean section, preterm normal spontaneous vaginal
      delivery and preterm caesarean section). Therefore, umbilical cord blood samples
      seem to be suitable for transplantation in metachromatic leukodystrophy,
      regardless of gestational age and mode of delivery. Moreover, our results are the
      first published data on normal values for arylsulfatase-A activity in human
      umbilical cord blood.

PMID- 11960266
TI  - Donation of stem cells from blood or bone marrow: results of a randomised study
      of safety and complaints.
AB  - Biological consequences and physical complaints were compared for donors randomly
      assigned either to blood stem cell (BSC) or bone marrow (BM) donation. In the
      period 1994-1999, 61 consecutive donors were included. The BSC donors were given
      G-CSF 10 microg/kg s.c., daily during 5 days before the first leukapheresis.
      Nineteen donors had one leukapheresis, 10 required two and one donor needed three
      leukaphereses in order to reach the target cell number of 2 x 10(6) CD34(+)
      cells/kg bw of the recipient. A median platelet nadir of 102 x 10(9)/l was
      reached shortly after the last leukapheresis. Three weeks post harvest, 17 of 30
      BSC donors had a mild leukopenia. Six had a leukopenia lasting more than a year
      before returning to normal values. Both groups were monitored prospectively
      through a standardised questionnaire completed by the donors. BSC donation was
      significantly less burdensome than BM donation and was preferred by the donors.
      The short-term risks of BSC mobilisation and harvest seem negligible. The
      potential long-term effects of G-CSF are unresolved and the donors must be
      followed closely.

PMID- 11960268
TI  - Outcome of second hematopoietic cell transplantation in Hurler syndrome.
AB  - Hurler syndrome (HS) is an autosomal recessive, inherited metabolic storage
      disorder due to deficiency of lysosomal alpha-L-iduronidase (IDU) enzyme
      activity. Untreated patients develop progressive mental retardation and
      multisystem morbidity with a median life expectancy of 5 years. Allogeneic
      hematopoietic cell transplantation (HCT) can achieve stabilization and even
      improvement of intellect, with long-term survival. However, children with HS have
      an increased incidence of graft failure, usually with concomitant autologous
      marrow reconstitution. Between 1983 and 2000, 71 Hurler children underwent HCT at
      the University of Minnesota. Of these 71, 19 (27%) experienced graft failure. We
      report HCT outcomes in all 11 Hurler patients receiving a second HCT at the
      University of Minnesota. Median age at second HCT was 25 months (range, 16 to 45
      months); median time from first HCT was 8 months (range, 4 to 18.5 months). The
      conditioning regimen consisted of cyclophosphamide/TBI/ATG (n = 8) or
      busulfan/cyclophosphamide/ATG (n = 3). The source of bone marrow was an unrelated
      donor in six, matched sibling in four, and mismatched related in one. Five of the
      11 grafts were T cell depleted prior to infusion. Overall, 10 of 11 patients
      showed donor-derived engraftment, of whom three developed grade 3 to 4 acute
      GVHD. Five of 11 patients are surviving a median of 25 months (range, 2 months to
      12 years) with an overall actuarial survival of 50% (95% CI, 27% to 93%) at 4
      years. All five show sustained donor engraftment with normalization of IDU
      activity levels. Three of five evaluable patients demonstrated stabilization of
      neuropsychological function after second HCT. Currently, allogeneic donor-derived
      hematopoiesis provides the only chance for long-term survival and improved
      quality of life in Hurler patients. While graft failure in Hurler patients
      requires further investigation, a timely second HCT can be well-tolerated and
      beneficial.

PMID- 11960269
TI  - Clinical scale isolation of T cell-depleted CD56+ donor lymphocytes in children.
AB  - We present a clinical scale method for immunomagnetic separation of CD56+ donor
      natural killer cells for adoptive immunotherapy of pediatric leukemias after
      allogeneic transplantation. This time-saving and partially automated procedure
      employed CD56+ selection followed by CD3+ depletion, resulting in a median purity
      of 98.6% NK cells and a four-log depletion of T cells. The enriched NK cells
      demonstrated high cytotoxic activity against K562 target cells and fresh leukemic
      blasts with low HLA class I expression, which could be further enhanced by IL-2
      stimulation. Lysis of NK-insensitive leukemic cells with high HLA class I
      expression could also be demonstrated via ADCC. Due to the high degree of T cell
      depletion, alloreactive proliferation in mixed lymphocyte cultures and response
      to T cell-specific mitogen stimulation was profoundly decreased. Our results
      suggest that, even in the case of mismatched donors, infusions of donor NK cells
      with extremely low T cell content may be a promising treatment option for
      leukemic minimal residual disease after allogeneic transplantation without risk
      of inducing severe GVHD.

PMID- 11960270
TI  - Cataracts in patients receiving stem cell transplantation after conditioning with
      total body irradiation.
AB  - One hundred and ninety-three patients with hematological malignancies and a
      follow-up > or =1 year, treated with stem cell transplantation (45 autologous, 99
      allogeneic T cell-depleted matched, 49 allogeneic T cell-depleted mismatched)
      from July 1985 to May 1998, were considered evaluable for the development of
      cataracts. Total body irradiation (TBI), administered either according to a
      hyperfractionated scheme (HTBI) or in a single dose (STBI), was employed in the
      conditioning regimens. HTBI was prescribed in 94% of patients undergoing
      allogeneic matched transplant, while STBI was used in 71% of patients receiving
      allogeneic mismatched and in all patients undergoing autologous transplant. The
      median follow-up was 7.56 years in the HTBI and 3.02 years in the STBI group.
      Among the different risk factors analyzed by univariate analysis only the TBI
      scheme and type of transplant reached statistical significance (P < 0.0001 and P
      < 0.001, respectively). By multivariate analysis only the TBI scheme was an
      independent factor for cataract development (STBI vs HTBI RR 7.2; P < 0.01). Our
      results showed that STBI is more cataractogenic than HTBI. The incidence of
      cataract we observed was among the lowest described in the literature. T cell
      depletion, because it prevents graft-versus-host disease and reduces the
      protracted use of post-transplant steroids, explains the results we obtained.

PMID- 11960271
TI  - Clinicopathological features and risk factors of clinically overt haemorrhagic
      cystitis complicating bone marrow transplantation.
AB  - Haemorrhagic cystitis (HC) is an important complication after bone marrow
      transplantation (BMT). Overt HC (grade > or =2, gross haematuria, clot retention
      and impairment of renal function), clinically more important than mild and occult
      HC (grade 1, microscopic haematuria), leads to substantial morbidity and
      occasional mortality. We retrospectively analyzed 32 cases of clinically overt HC
      from a series of 236 BMT patients. Significant risk factors included the use of
      busulphan during conditioning, allogeneic BMT and acute GVHD. Logistic regression
      showed GVHD to be the most important risk factor. According to the time of
      engraftment, HC could be divided into pre- and post-engraftment subtypes. Pre
      engraftment HC was brief, not more severe than grade 2, and subsided with
      supportive treatment. In contrast, post-engraftment HC was protracted, often of
      grade > or =3, associated with severe GVHD, and required surgical intervention in
      many cases. Polyoma BK viruria, but not adenoviruria, could be demonstrated in
      both types of HC. The increased severity and association with GVHD of post
      engraftment HC suggested that attack of urothelium by immunocompetent cells,
      possibly directed against BK viral antigens, might play a pathogenetic role.

PMID- 11960272
TI  - Guillain-Barre syndrome after allogeneic hematopoietic stem cell transplantation.
AB  - Guillain-Barre syndrome is a rare complication in the setting of hematopoietic
      stem cell transplantation. We report three children with T cell lymphoma/leukemia
      in whom this syndrome developed soon after they received unrelated donor
      transplants. The rapid onset of symptoms raises the concern that the bone marrow
      transplant conditioning regimen (ie, total body irradiation, cyclophosphamide and
      cytosine arabinoside) might have precipitated the clinical syndrome of ascending
      polyneuropathy. Although central nervous system toxicity has been well described
      with high-dose cytosine arabinoside therapy, peripheral neuropathy of the
      Guillain-Barre type has been reported only infrequently. We review possible
      factors contributing to the development of this syndrome in these three patients.

PMID- 11960273
TI  - Allogeneic bone marrow transplantation for active Epstein-Barr virus-related
      lymphoproliferative disease and hemophagocytic lymphohistiocytosis in an infant
      with severe combined immunodeficiency syndrome.
AB  - A 5-month-old male presented with fever, hepatosplenomegaly, leukocytosis with
      atypical lymphoblasts, anemia and thrombocytopenia. Severe combined
      imunodeficiency syndrome (T-, B+, NK+), B lymphoproliferative disease and
      hemophagocytic lymphohistiocytosis triggered by Epstein-Barr virus (EBV) were
      diagnosed. As his clinical situation deteriorated rapidly, BMT was performed with
      unmanipulated marrow stem cells from his EBV-positive HLA-identical sister after
      conditioning with dexamethasone (1.75 mg/kg/day), cyclophosphamide (114 mg/kg)
      and etoposide (10 mg/kg), with no immunosuppression given post transplant.
      Engraftment occurred on day 6 with explosive proliferation of donor CD8(+) T
      cells. The patient died 3 days later from acute respiratory distress syndrome.
      Autopsy revealed full donor engraftment and no signs of hemophagocytic
      lymphohistiocytosis or B lymphoproliferative disease. Thus, transplanted T cells
      can expand very rapidly within days after BMT and clear EBV lymphoproliferative
      disease and hemophagocytic lymphohistiocytosis.

PMID- 11960274
TI  - Successful autologous peripheral blood stem cell transplantation in transformed
      follicular lymphoma previously treated with radioimmunotherapy (iodine (131)I
      tositumomab).
AB  - While the use of radioimmunotherapy for lymphoma increases, the feasibility and
      efficacy of autologous stem cell transplant for subsequent relapse remains
      unknown. We report a 48-year-old male with transformed follicular mixed non
      Hodgkin's lymphoma. After treatment with three different combination chemotherapy
      regimens, at relapse he received radioimmunotherapy with iodine (131)I
      tositumomab (anti-CD20), with very good response. At later relapse, a second
      course of (131)I tositumomab was given unsuccessfully. He underwent peripheral
      blood stem cell harvest, chemoradiotherapy conditioning and autologous
      transplantation with prompt engraftment and without significant complications. He
      remains in complete remission with normal blood counts 25 months post autograft.

PMID- 11960275
TI  - Non-invasive determination of the paternal HLA haplotype of a fetus using kinetic
      PCR to detect fetal microchimerism in maternal plasma.
AB  - Knowledge of fetal HLA type can be important if cord blood (CB) is being
      considered as a stem cell source for transplantation. The feasibility of
      determining the paternally inherited HLA haplotype of a fetus was explored
      through analysis of fetal DNA in the maternal circulation. A 5-year-old child
      with relapsed acute leukemia was a candidate for transplantation. The HLA type of
      the fetal sibling was needed to assist with evaluation of this potential cord
      blood donor. DNA was isolated from maternal plasma and whole blood. Kinetic PCR
      using sequence-specific primers for paternal HLA-A, -B, and -DRB1 alleles was
      performed. Alleles corresponding to one paternal haplotype were detectable in
      plasma, but not in whole blood. Alleles from the alternative haplotype were not
      detectable. This demonstrated that the fetus shared at least one haplotype with
      the patient and therefore arrangements were made to bank the CB. The maternal
      haplotype of the fetus could not be determined in the presence of maternal DNA.
      The prenatal fetal typing was confirmed by typing the newborn's CB. This rapid
      non-invasive technique may facilitate the selection of CB units for banking based
      on needed HLA types.

PMID- 11960276
TI  - Chronic active Epstein-Barr virus infection (CAEBV) successfully treated with
      allogeneic peripheral blood stem cell transplantation.
AB  - We report a pediatric case of CAEBV and T cell-based Hodgkin's-like disease
      successfully treated with allo PBSCT from an HLA-matched sibling. The diagnosis
      of CAEBV was made from clinical signs and the presence of the EBV genome in PBMC
      and tumor cells. Conditioning with busulfan (BU) + etoposide (VP16) +
      cyclophosphamide (CY) was effective and well tolerated. EBV was totally
      eradicated by 3 months after allo PBSCT. Although she suffered from chronic GVHD
      of the liver, she has been well and free of disease for 47 months since PBSCT. We
      suggest allo PBSCT for CAEBV as a potent therapeutic strategy for eradication of
      the EBV genome and allowing immunological reconstitution.

PMID- 11960277
TI  - Elevated blood drug levels obtained from indwelling silicon catheters during oral
      cyclosporine A administration.
AB  - Cyclosporine A (CsA) may be bound to and released from the inner surface of
      central venous catheters resulting in spuriously elevated blood drug levels. We
      observed this phenomenon in a boy transplanted because of aplastic anemia up to 9
      weeks after CsA had been switched from intravenous to oral administration. In
      comparison to phlebotomy, simultaneous blood sampling from the double lumen
      catheter resulted in a greater than 10-fold, or two-fold increase in drug levels,
      respectively, depending on whether or not the line used for prior CsA infusion
      was selected. Thus, prolonged binding of CsA to the inner surface of venous
      catheters should also be considered during oral administration.

PMID- 11960279
TI  - Human parainfluenza type 4 infection: a case report highlighting pathogenicity
      and difficulties in rapid diagnosis in the post-transplant setting.

PMID- 11960278
TI  - Dental development after successful treatment of infantile osteopetrosis with
      bone marrow transplantation.
AB  - A 3-week-old boy was diagnosed with congenital osteopetrosis. He underwent a bone
      marrow transplant at 6 weeks of age. At 3 years of age the primary teeth had all
      erupted, but the canines and the first molars totally lacked root development.
      The teeth were smaller in size and had evidence of both enamel hypomineralization
      and hypoplasia. In the permanent dentition, multiple missing teeth were found.
      The incisors were conical and the mandibular laterals were extremely small. All
      permanent teeth had normal eruption. This case shows that dental development and
      eruption of teeth can be reconstituted in a child with congenital osteopetrosis.
      Bone marrow transplantation induces normalization of osteoclast function, which
      is a prerequisite for normal dental development and eruption of teeth.

PMID- 11960280
TI  - Defibrotide as a promising treatment for thrombotic thrombocytopenic purpura in
      patients undergoing bone marrow transplantation.

PMID- 11960281
TI  - Epileptic seizures after autologous peripheral blood progenitor infusion in a
      patient treated with high-dose chemotherapy for myeloma.

PMID- 11960282
TI  - Cancer therapy utilizing an adenoviral vector expressing only E1A.
AB  - The human adenovirus type 5 (Ad5) early region 1A (E1A) proteins have been shown
      to have potent antitumor effects, due to their ability to reprogram oncogenic
      signalling pathways in tumor cells. The success of E1A antitumor therapy in
      animal models has led to its use in phase I and phase II clinical trials, where
      liposome-based delivery vehicles are being used to deliver a plasmid encoding
      E1A. To increase the efficiency of E1A delivery to tumors, we have developed an
      Ad vector deleted of all viral protein coding sequences (termed helper-dependent
      Ad vectors, hdAds) with the exception of E1A, designated hdAd-E1A. In culture,
      this vector mediated high-level expression of E1A gene products. A549 cells, a
      human lung adenocarcinoma cell line, infected with hdAd-E1A showed a reduced
      proliferative capacity in adherent culture, and the ability to form colonies in
      soft agarose was completely abolished. In contrast, A549 infected with an hdAd
      expressing beta-gal were able to form colonies of a similar size and frequency as
      uninfected cells. Under serum-depleted conditions, expression of E1A within A549
      led to the induction of apoptosis. Finally, A549 cells treated with hdAd-E1A
      showed approximately 10-fold greater sensitivity to the chemotherapeutic drug
      cisplatin. Taken together, these data indicate that the use of hdAd provides a
      simple and effective method to deliver E1A to cancer cells, and results in
      reduction in the tumorigenic potential of the cells, as well as increasing the
      cells sensitivity to anticancer drugs.

PMID- 11960283
TI  - Novel vaccination protocol consisting of injecting MUC1 DNA and nonprimed
      dendritic cells at the same region greatly enhanced MUC1-specific antitumor
      immunity in a murine model.
AB  - In order to induce specific antitumor immunity in mice, we attempted to immunize
      C57BL/6 mice with DNA vaccine encoding MUC1 polypeptide. When the mice immunized
      with MUC1 DNA were challenged with EL4-muc, MUC1-transfected syngeneic lymphoma
      cells, they completely rejected tumors. When DNA vaccine was given to the EL4-muc
      tumor-bearing mice, this vaccination was insufficient to suppress tumor growth in
      the mice. However, activated, but nonprimed dendritic cells (DCs) obtained from
      syngeneic mice and MUC1 DNA vaccine were given simultaneously to the same site of
      EL4-muc tumor-bearing mice, tumor growth was markedly suppressed accompanying
      prolongation of survival time. MUC1 antigen was detected on the DCs at the
      vaccination site and in regional nodes in the mice which received MUC1 DNA
      vaccine and DCs. These mice showed markedly enhanced cellular immune responses
      specific for MUC1 compared to those in mice vaccinated with MUC1 DNA alone. No
      significant difference in titers of antibodies to MUC1 between the two groups was
      observed. These results suggest that nonprimed DCs inoculated at the DNA vaccine
      site are essential for eliciting strong antitumor cellular immunity to suppress
      tumor growth efficiently in DNA-vaccinated mice. This animal model is useful for
      developing DNA vaccine for anti-cancer immunotherapy.

PMID- 11960284
TI  - Early gene therapy-induced apoptotic response in BT4C gliomas by magnetic
      resonance relaxation contrast T1 in the rotating frame.
AB  - The design and evaluation of therapeutic gene transfection protocols and vectors
      are under extensive development. Magnetic resonance imaging (MRI) techniques can
      aid considerably in the development of experimental treatment approaches, as well
      as in determining treatment response by observing gross tissue morphology.
      However, through a unique set of contrast parameters, namely T1, T2, and
      diffusion, more information about tissue status can be obtained while delineating
      and classifying tumor characteristics in more detail. We show here that T1
      relaxation in the rotating frame, T1rho, provides unique in vivo MRI contrast.
      Ganciclovir treatment of HSV-tk+BT4C gliomas, which effectively eradicates these
      tumors, resulted in significantly prolonged T1rho relaxation times in MRI already
      after 3 days of treatment, whereas conventional contrast parameters were elevated
      after 6-8 days of therapy. Interestingly, the prolonged T1rho values were
      observed while an increase in tumor volume was still taking place. The regions of
      elevated T1rho relaxation coincided with high apoptotic activity as determined by
      histology, suggesting that T1rho MRI contrast could be used as a novel early
      indicator of cytotoxic cell damage in gliomas.

PMID- 11960285
TI  - DNA vaccination with AFP-encoding plasmid DNA prevents growth of subcutaneous AFP
      expressing tumors and does not interfere with liver regeneration in mice.
AB  - The oncofetal alpha-fetoprotein (AFP) is reexpressed in the majority of
      hepatocellular carcinomas and may be used as a target molecule for an
      immunotherapy or prophylaxis against this tumor. We investigated the potential of
      DNA vaccination with AFP-expressing plasmid DNA to induce an immune response
      against AFP-expressing tumor cells in DBA/2 mice. 62.5% of mice vaccinated with
      AFP-expressing plasmid DNA, rejected subcutaneous syngeneic AFP-expressing P815
      tumors, whereas only 16.7% of mice vaccinated with control plasmid rejected these
      tumor cells (P=.03). Mean survival of mice after challenge with subcutaneous AFP
      expressing tumor cells was prolonged for 8 days in mice vaccinated with AFP
      expressing DNA (35 days) compared to mice vaccinated with control plasmid (27
      days). To rule out possible autoimmune reactions against regenerating liver,
      which also reexpresses AFP, we evaluated the influence of AFP-specific DNA
      vaccination on liver regeneration in DBA/2 mice. Histologic quantification of
      proliferating hepatocytes and of the amount of necrotic liver tissue in carbon
      tetrachloride-damaged liver did not reveal statistically significant differences
      in mice vaccinated with AFP-expressing plasmid compared to control mice. These
      data suggest that AFP-specific DNA vaccination represents a useful tool to
      inhibit growth of AFP-expressing tumors in mice that does not affect liver
      regeneration.

PMID- 11960286
TI  - Immuno-viral therapy of brain tumors by combination of viral therapy with cancer
      vaccination using a replication-conditional HSV.
AB  - Here we developed an effective therapeutic approach using a replication
      conditional mutant of herpes simplex virus (HSV), G207, for the treatment of
      metastatic tumors in the immunologically privileged central nervous system. An
      experimental model of brain metastasis was developed using BALB/c mice that
      harbored both intracranial (i.c.) and subcutaneous (s.c.) mouse CT26 colon
      adenocarcinoma tumors. Intratumoral injections of G207 into s.c. tumors elicited
      cytotoxic T-cell responses not only to HSV but also to a tumor antigen; however,
      only a limited antitumor effect was observed on metastatic brain tumors. To
      improve this antitumor effect, G207 was also injected into the brain tumor. After
      intratumoral injections of G207 into both i.c. and s.c. CT26 tumors, a
      significant antitumor effect was observed in the metastatic brain tumors. This
      therapeutic efficacy was absent in athymic mice, indicating that the antitumor
      effect could be mediated by T cells. Cytotoxic T-cell responses to HSV and the
      tumor antigen were induced by injections of G207 into i.c. and s.c. CT26 tumors.
      These results suggest that HSV-infected brain tumors may be efficiently
      eliminated by the induced anti-HSV T cells as well as by antitumor T cells.
      Therefore, this strategy of immuno-viral therapy, involving direct viral
      oncolytic activities and inducing antitumor and antiviral immune responses, may
      be useful for the treatment of tumors in the immunologically privileged central
      nervous system.

PMID- 11960287
TI  - Light-induced adenovirus gene transfer, an efficient and specific gene delivery
      technology for cancer gene therapy.
AB  - A main issue for further clinical progress of cancer gene therapy is to develop
      technologies for efficient and specific delivery of therapeutic genes to tumor
      cells. In this work, we describe a photochemical treatment that substantially
      improves gene delivery by adenovirus, one of the most efficient gene delivery
      vectors known. Transduction of two different cell lines was studied by
      microscopy, flow cytometry, and an enzymatic assay, employing a beta
      galactosidase-encoding adenovirus. The photochemical treatment induced a >20-fold
      increase in gene transduction, compared with conventional adenovirus infection,
      both when measured as the percentage of cells transduced, and when measured as
      the total beta-galactosidase activity in the cell population. The effect was most
      pronounced at lower virus doses, where in some cases the same transduction
      efficiency could be achieved with a 20 times lower virus dose than with
      conventional infection. Photochemical treatments are already in clinical use for
      cancer therapy, and generally are very specific and have few side effects. The
      photochemical internalization technology described thus has a clear potential for
      improving both the efficiency and the specificity of gene delivery in cancer gene
      therapy, making it possible to achieve efficient site-specific in vivo gene
      delivery by adenoviral vectors.

PMID- 11960288
TI  - TRAIL enhances thymidine kinase/ganciclovir gene therapy of neuroblastoma cells.
AB  - The clinical benefit of suicide gene therapy of tumors has been marginal, mostly
      due to the low gene transfer efficiency in vivo. The death-inducing ligand,
      TRAIL, effectively kills many tumor cell types, while sparing most normal
      tissues. We hypothesized that TRAIL may enhance HSV thymidine kinase/ganciclovir
      (TK/GCV) gene therapy of tumor cells by augmenting both target and bystander cell
      kill. Human SH-EP neuroblastoma cells expressing TK as well as bystander cells
      were effectively killed by apoptosis, and their clonogenicity was ablated
      following GCV. Human TRAIL enhanced TK/GCV-induced cell death and decreased
      clonogenicity of TK-expressing cells and also of bystander cells. Cooperation
      between TRAIL and TK/GCV depended both on caspase activation and on mitochondrial
      apoptogenic function because both the broad-spectrum caspase inhibitor zVAD.fmk
      and overexpression of Bcl-2 decreased enhancement of cell kill by TRAIL.
      Facilitation of TRAIL signalling by up-regulation of TRAIL receptors did not
      contribute to enhancement because cell surface expression of the agonistic TRAIL
      receptors 1 and 2 was not increased by TK/GCV. In conclusion, the concerted
      activation of caspases and the mitochondrial amplification of caspase activation
      by TK/GCV may explain the cooperative effect of TK/GCV and TRAIL on the kill of
      neuroblastoma cells. Because combined treatment also augmented the bystander cell
      kill, the addition of TRAIL may increase the efficacy of TK/GCV gene therapy of
      neuroblastoma.

PMID- 11960289
TI  - Inhibition of tumor growth by recombinant vaccinia virus expressing GA733/CO17
      1A/EpCAM/KSA/KS1-4 antigen in mice.
AB  - The human colorectal carcinoma (CRC)-associated GA733 antigen (Ag), also named
      CO17-1A/EpCAM/KSA/KS1-4, has been a useful target in passive immunotherapy of CRC
      patients with monoclonal antibody (mAb) and in active immunotherapy with anti
      idiotypic antibodies or with recombinant protein. These approaches have targeted
      single epitopes (monoclonal anti-GA733 antibodies and anti-idiotypic antibodies)
      or extracellular domain epitopes (recombinant protein), primarily by B cells. To
      determine whether a reagent that induces immunity to a larger number of both B-
      and T-cell epitopes might represent a superior vaccine, we analyzed the capacity
      of full-length GA733 Ag expressing multiple potentially immunogenic epitopes and
      encoded by recombinant vaccinia virus (VV GA733-2) to induce humoral, cellular,
      and/or protective immunity in mice. VV GA733-2 induced Ag-specific antibodies
      that reacted predominantly to unknown epitopes on the Ag and lysed Ag-positive
      CRC targets in conjunction with murine peritoneal macrophages as effector cells.
      Immunized mice developed Ag-specific, proliferative and delayed-type
      hypersensitive lymphocytes. VV GA733-2 inhibited growth of ras-transformed
      syngeneic tumor cells expressing the human GA733 Ag in mice. These results
      suggest the potential of VV GA733-2 as a candidate vaccine for patients with CRC,
      possibly in combination with recombinant GA733-2-expressing adenovirus, which has
      been shown to induce cytolytic antibodies and T cells as well as tumor protective
      effects in mice. The combined vaccine approach may be superior to the use of
      either vaccine alone in patients who are pre-immune to both viruses.

PMID- 11960290
TI  - Human natural killer cell line modified with a chimeric immunoglobulin T-cell
      receptor gene leads to tumor growth inhibition in vivo.
AB  - The gene transfer of tumor-specific chimeric immunoglobulin T-cell receptors
      (cIgTCRs) combining antibody-like specificity with the effector cell function
      could be an attractive tool in immunotherapy. In this study, we directed the
      human natural killer (NK) cell line YT to tumor cells by gene transfer of a
      cIgTCR with specificity against the human carcinoembryonic antigen (CEA). The
      cIgTCR was constructed of a CEA-specific humanized single-chain Fv antibody
      fragment fused to the IgG1 Fc domain and the CD3 zeta chain. YT cells were
      transfected with the cIgTCR gene by electroporation and cIgTCR-expressing cells
      were enriched by immunoaffinity purification. cIgTCR-expressing YT cells
      specifically lysed CEA(+) colon carcinoma cell lines, which were resistant to the
      parental YT cell line. The lysis was not inhibited in the presence of soluble
      CEA. Receptor gene-modified YT cells retained their CEA-specific cytolytic
      activity after gamma-irradiation in vitro and inhibited the tumor growth in vivo
      after adoptive transfer into NOD/SCID mice. This gene-modified NK cell line
      available in unlimited source might be useful in clinical immunotherapy of CEA(+)
      cancer.

PMID- 11960291
TI  - Effective gene transfer to solid tumors using different nonviral gene delivery
      techniques: electroporation, liposomes, and integrin-targeted vector.
AB  - In this study, we measured transfection efficiency in vitro and in vivo using the
      following nonviral approaches of gene delivery: injection of plasmid DNA,
      electroporation-assisted, liposome-enhanced, and integrin-targeted gene delivery,
      as well as the combination of these methods. Four histologically different tumor
      models were transfected with a plasmid encoding the green fluorescent protein
      (GFP) (B16 mouse melanoma, P22 rat carcinosarcoma, SaF mouse sarcoma, and T24
      human bladder carcinoma) using adherent cells, dense cell suspensions, and solid
      tumors. Emphasis was placed on different electroporation conditions to optimise
      the duration and amplitude of the electric pulses, as well as on different DNA
      concentrations for effective gene delivery. In addition, transfection efficiency
      was correlated with cell density of the tumors. The major in vivo findings were:
      (a) electroporation-assisted gene delivery with plasmid DNA, employing long
      electric pulses with low amplitude, yielded significantly better GFP expression
      than short electric pulses with high amplitude; (b) electroporation combined with
      liposome-DNA complexes yielded the highest percentage of transfected tumor area
      in B16F1 tumor (6%); (c) transfection efficiency of electroporation-assisted
      plasmid DNA delivery was dependent on tumor type; (d) integrin-targeted vector,
      alone or combined with electroporation, was largely ineffective. In conclusion,
      our results demonstrate that some nonviral methods of gene delivery are feasible
      and efficient in transfecting solid tumors. Therefore, this makes nonviral
      methods attractive for further development.

PMID- 11960292
TI  - Fatty acid analysis of wild ruminant tissues: evolutionary implications for
      reducing diet-related chronic disease.
AB  - HYPOTHESES: Consumption of wild ruminant fat represented the primary lipid source
      for pre-agricultural humans. Hence, the lipid composition of these animals'
      tissues may provide insight into dietary requirements that offer protection from
      chronic disease in modern humans. METHOD: We examined the lipid composition of
      muscle, brain, marrow and subcutaneous adipose tissue (AT) from 17 elk (Cervus
      elaphus), 15 mule deer (Odocoileus hemionus), and 17 antelope (Antilicapra
      americana) and contrasted them to wild African ruminants and pasture and grain
      fed cattle. RESULTS: Muscle fatty acid (FA) was similar among North American
      species with polyunsaturated fatty acids/saturated fatty acids (P/S) values from
      0.80 to 1.09 and n-6/n-3 FA from 2.32 to 2.60. Marrow FA was similar among North
      American species with high levels (59.3-67.0%) of monounsaturated FA; a low P/S
      (0.24-0.33), and an n-6/n-3 of 2.24-2.88. Brain had the lowest n-6/n-3 (1.20
      1.29), the highest concentration of 22:6 n-3 (elk, 8.90%; deer, 9.62%; antelope,
      9.25%) and a P/S of 0.69. AT had the lowest P/S (0.05-0.09) and n-6/n-3 (2.25
      2.96). Conjugated linoleic acid (CLA) isomers were found in marrow of antelope
      (1.5%), elk (1.0%) and deer (1.0%), in AT (deer, 0.3%; antelope, 0.3%) in muscle
      (antelope, 0.4%; elk, trace), but not in brain. CONCLUSIONS: Literature
      comparisons showed tissue lipids of North American and African ruminants were
      similar to pasture-fed cattle, but dissimilar to grain-fed cattle. The lipid
      composition of wild ruminant tissues may serve as a model for dietary lipid
      recommendations in treating and preventing chronic disease.

PMID- 11960293
TI  - Anemia in pregnancy in rural Tanzania: associations with micronutrients status
      and infections.
AB  - OBJECTIVE: We studied the association between anemia in pregnancy and
      characteristics related to nutrition and infections. DESIGN: Cross-sectional
      study. SETTING: Four antenatal clinics in rural northern Tanzania.
      SUBJECTS/METHODS: A total of 2547 women were screened for hemoglobin (Hb) and
      malaria plasmodia in capillary blood and for infections in urine. According to
      their Hb, they were assigned to one of five groups and selected accordingly,
      Hb<70 g/l (n=10), Hb=70-89 g/l (n=61), Hb=90-109 g/l (n=86), Hb=110-149 g/l
      (n=105) and Hb> or =150 g/l (n=50). The 312 selected subjects had venous blood
      drawn, were interviewed, and their arm circumference was measured. The sera were
      analyzed for ferritin, iron, total iron binding capacity (TIBC), cobalamin,
      folate, vitamin A, C-reactive protein (CRP), and lactate dehydrogenase (LD).
      Transferrin saturation (TFsat) was calculated. Urine was examined by dipsticks
      for nitrite. MAIN OUTCOME MEASURES: Unadjusted and adjusted odds ratio (OR and
      AOR) of anemia with Hb<90 g/l. RESULTS: Anemia (Hb<90 g/l) was associated with
      iron deficiency (low s-ferritin; AOR 3.4). The association with vitamin
      deficiencies were significant in unadjusted analysis (low s-folate; OR 3.1, low s
      vitamin A; OR 2.6). Anemia was also associated with markers of infections
      (elevated s-CRP; AOR 3.5, urine nitrite positive; AOR 2.4) and hemolysis
      (elevated s-LD; AOR 10.1). A malaria positive blood slide was associated with
      anemia in unadjusted analysis (OR 2.7). An arm circumference less than 25 cm was
      associated with anemia (AOR 4.0). The associations with less severe anemia (Hb 90
      109 g/l) were similar, but weaker. CONCLUSIONS: Anemia in pregnancy was
      associated with markers of infections and nutritional deficiencies. This should
      be taken into account in the management of anemia at antenatal clinics.
      SPONSORSHIP: The study was supported by the Norwegian Research Council (NFR) and
      the Centre for International Health, University of Bergen.

PMID- 11960294
TI  - Trends in overweight and obesity prevalence in Chilean children: comparison of
      three definitions.
AB  - OBJECTIVE: To compare trends in prevalence of overweight and obesity among
      Chilean children using three different criteria. METHODS: Descriptive cross
      sectional school-based study to analyse these trends in 6-y-old boys and girls
      who entered first grade in 1987, 1990, 1993, 1996 and 2000. Gender-specific
      prevalence of overweight and obesity were determined with three criteria: weight
      for height (W-H) Z-scores compared to NCHS 1977; present reference used by the
      Ministry of Health; and body mass index (BMI) compared to the revised US CDC
      Growth Charts with cut-off values of P85-95 and P-95 and IOTF reference with cut
      offs extrapolated from an adult BMI of 25 and 30. RESULTS: The prevalence of
      overweight determined by W-H (WHO) increased from 15% in 1987 to 20% in 2000 for
      boys and from 17.2 to 21.8% for girls. With BMI-CDC, the increase was from 13.2
      to 19.2% for boys and 12 to 18.5% for girls. With BMI-IOTF, rates were very
      similar. Prevalence of obesity using W-H (WHO) increased from 6.5% in 1987 to 17%
      in 2000 for boys and from 7.8 to 18.6% for girls. Using BMI-CDC, the increase was
      from 5.1 to 14.7% for boys and from 4 to 15.8% for girls; using BMI-IOTF
      prevalence estimates were much lower. CONCLUSIONS: Obesity prevalence in children
      has increased over time, and trends are similar independent of criteria. The
      reference used to define prevalence is important since it provides different
      estimates. Policy makers should be aware that a spurious drop in prevalence may
      appear if the IOTF reference is compared to the other criteria.

PMID- 11960295
TI  - Energy intake and expenditure of free-living, lactating Colombian women in an
      urban setting.
AB  - OBJECTIVES: To examine the components of energy balance during lactation in a
      population of economically disadvantaged women in an urban developing country
      setting in order to better understand the metabolic response to lactation.
      DESIGN: Cross-sectional comparison of lactating (LACT) and non-pregnant non
      lactating (NPNL) women. Body size and composition were assessed via
      anthropometry, energy intake was measured using estimated diet records and energy
      expenditure using indirect calorimetry and the Flex-Heart Rate method. SETTING:
      Low-income neighborhoods of Cali, Colombia. SUBJECTS: Lactating women (n=15)
      studied at 2.4+/-0.8, 5.5+/-0.8 and 8.9+/-1.2 months postpartum, and NPNL women
      (n=48) studied in three measurement rounds at 0, 3.5+/-0.6 and 7.1+/-1.0 months.
      RESULTS: There were no significant differences between LACT and NPNL women in
      anthropometric dimensions, but LACT women showed decreases in waist-hip ratio,
      lean body mass and increases in mid-arm circumference and percentage body fat
      with time. Energy intake was higher in LACT women (P=0.04), but there were no
      significant between-group differences in energy expenditure variables.
      CONCLUSION: This group of women met the cost of lactation principally via
      increased energy intake.

PMID- 11960296
TI  - Validity of total and segmental impedance measurements for prediction of body
      composition across ethnic population groups.
AB  - OBJECTIVES: To test the impact of body build factors on the validity of impedance
      based body composition predictions across (ethnic) population groups and to study
      the suitability of segmental impedance measurements. DESIGN: Cross-sectional
      observational study. SETTINGS: Ministry of Health and School of Physical
      Education, Nanyang Technological University, Singapore. SUBJECTS: A total of 291
      female and male Chinese, Malays and Indian Singaporeans, aged 18-69, body mass
      index (BMI) 16.0-40.2 kg/ m2. METHODS: Anthropometric parameters were measured in
      addition to impedance (100 kHz) of the total body, arms and legs. Impedance
      indexes were calculated as height2/impedance. Arm length (span) and leg length
      (sitting height), wrist and knee width were measured from which body build
      indices were calculated. Total body water (TBW) was measured using deuterium
      oxide dilution. Extra cellular water (ECW) was measured using bromide dilution.
      Body fat percentage was determined using a chemical four-compartment model.
      RESULTS: The bias of TBW predicted from total body impedance index (bias:
      measured minus predicted TBW) was different among the three ethnic groups, TBW
      being significantly underestimated in Indians compared to Chinese and Malays.
      This bias was found to be dependent on body water distribution (ECW/TBW) and
      parameters of body build, mainly relative (to height) arm length. After
      correcting for differences in body water distribution and body build parameters
      the differences in bias across the ethnic groups disappeared. The impedance index
      using total body impedance was better correlated with TBW than the impedance
      index of arm or leg impedance, even after corrections for body build parameters.
      CONCLUSIONS: The study shows that ethnic-specific bias of impedance-based
      prediction formulas for body composition is due mainly to differences in body
      build among the ethnic groups. This means that the use of 'general' prediction
      equations across different (ethnic) population groups without prior testing of
      their validity should be avoided. Total body impedance has higher predictive
      value than segmental impedance.

PMID- 11960297
TI  - The effect of nutritional intervention in elderly subjects residing in group
      living for the demented.
AB  - OBJECTIVES: We studied the nutritional status and the effects of nutritional
      intervention on body weight, cognition and activities of daily life (ADL)
      function in demented individuals. DESIGN: Controlled non-randomised study.
      SETTING: Group-living for demented elderly (GLD), ie community assisted housing.
      SUBJECTS AND INTERVENTIONS: Twenty-two residents living in one of two units (GLD
      I), received oral liquid supplements (1720 kJ/410 kcal/day) and the personnel of
      the GLD-I were given nutritional education. Fourteen residents in the other unit
      (GLD-C) served as controls. After 6 months 21 (83 (4) y, 81% women) and 12 (85
      (4) y, 100% women) of the participants, respectively, were re-examined according
      to body mass index (BMI, kg/m2), cognitive function (Mini Mental State
      Examination (MMSE, 0-30 p) and Clinical Dementia Rating Scale (CDR) and the Katz'
      ADL index. RESULTS: Body mass index (BMI) < or =20 was found in 19% of the
      participants and 44% had BMI< or =23. BMI correlated with MMSE (r=0.43, P<0.01).
      The weight of the residents in the intervention group increased by 3.4 (3) kg
      (P=0.001) at follow-up, whereas the weight remained unchanged in the control
      group. The cognitive function was low at the start in both groups, ie MMSE
      approximately 9 and no apparent positive effect of the nutritional intervention
      was seen. In addition, the ADL functions appeared to deteriorate in both groups.
      CONCLUSIONS: Being underweight was common among demented elderly in group-living
      and was related to low cognitive capacity. Five months of oral supplementation,
      along with education of personnel, was followed by a weight gain. In this study
      the nutritional treatment did not affect the rate of decline in cognitive
      function or Katz' ADL index. SPONSORSHIP: Supported by grants from the Swedish
      National Board of Health and Social Welfare. Semper Foods AB provided the liquid
      supplements.

PMID- 11960298
TI  - Calcium, phosphorus and magnesium balance: FM 85 fortification of human milk does
      not meet mineral needs of extremely low birthweight infants.
AB  - OBJECTIVE: Extremely low birthweight (<1000 g) infants are growing rapidly and
      their nutritional requirements for calcium, phosphorus, magnesium are high.
      DESIGN: Prospective, mineral balance. SETTING: The study was carried out at the
      Department of Neonatology, Virchow-Hospital, Charite Berlin and the Department of
      Molecular Trace Element Research, Hahn-Meitner-Institute Berlin. SUBJECTS:
      Nineteen infants <1000 g birthweight were admitted, nine infants dropped out and
      10 infants (birthweight 730-995 g), fed fortified human milk were included.
      INTERVENTION: We collected infant's urine and feces for 72 h, a sample of human
      milk and infant's blood at 7 and 12 weeks of age. Elements were measured by
      inductively coupled plasma atomic emission spectrophotometry. RESULTS: Mean
      (s.d.) mineral concentration in milk was low especially at 12 weeks: calcium 9.88
      (+/-3.58) mmol/l, phosphorus 7.02 (+/-3.81) mmol/l, magnesium 1.59 (+/-0.54)
      mmol/l. Calcium retention was minimal or negative during the study, whereas
      phosphorus and magnesium balances were positive. Caffeine and diuretics increased
      mineral excretion. Serum alkaline phosphatase was mostly <800 U/l, and 162 U/l in
      one infant with zinc deficiency at 12 weeks. Alkaline phosphatase correlated with
      absorption and retention of phosphorus, and with longitudinal growth.
      CONCLUSIONS: Infants <1000 g have high nutritional needs for calcium, phosphorus
      and magnesium, which are not met by a human milk fortifier widely used in Europe.
      Controlled trials are needed to assess requirements, duration and risks of
      mineral supplementation.

PMID- 11960299
TI  - Drinks consumed by 18-month-old children: are current recommendations being
      followed?
AB  - OBJECTIVE: To examine the types of drinks consumed by children at 18 months of
      age, determine any associations with socio-demographic characteristics and
      investigate the use of a bottle for providing these drinks. DESIGN: A total of
      1026 randomly chosen children from the Avon Longitudinal Study of Pregnancy and
      Childhood (ALSPAC) were studied. METHODS: As part of a dietary diary completed
      when their children were 18 months of age, mothers were asked to record all
      drinks consumed over a 24 h period and to report the containers used to give
      these drinks. Socio-demographic characteristics were obtained via self-completion
      questionnaire. RESULTS: Dietary records were available for 1026 children at 18
      months. A wide variety of drinks were given at this age. In all, 64% of children
      had received at least one drink in a bottle and 10% solely used a bottle. Bottle
      users consumed a significantly greater volume of milk drinks compared to those
      who used a cup or other container. The types of drinks consumed and adherence to
      the guidelines on weaning were associated with several socio-demographic
      characteristics. In particular, children with mothers of lower educational level
      were more likely to receive fizzy drinks and low-calorie soft drinks, more likely
      to drink from a bottle, and less likely to drink from a cup. CONCLUSION: We have
      shown that certain groups of mothers with 18-month-old children are not following
      the current guidelines on weaning. Assuming these guidelines have scientific
      validity, it is clear that nutritional education needs to be targeted at these
      mothers to help them feed their children in the optimal way, to protect from
      nutritional deficiencies, possible later obesity and poor dental health.
      SPONSORSHIP: University of Bristol.

PMID- 11960300
TI  - Study of the effect of a liquid nutrition supplement on the nutritional status of
      psycho-geriatric nursing home patients.
AB  - OBJECTIVES: To evaluate the acceptance of a multinutrient liquid nutrition
      supplement in psycho-geriatric nursing home patients and the effect on weight,
      plasma nutrients and activities of daily life. DESIGN: Double-blind, placebo
      controlled 12-week intervention study. SETTING: Two nursing homes in Boxtel, The
      Netherlands. SUBJECTS: Forty-two (body mass index (BMI) <23 kg/m2 for men or <25
      kg/m2 for women) psycho-geriatric nursing home patients aged 60 y or over.
      INTERVENTIONS: Provision with a complete micronutrient-enriched liquid nutrition
      supplement of 125 ml and 0.6 MJ (135 kcal) or placebo twice daily during daytime
      between main meals. Study parameters were assessed at 0, 6 and 12 weeks. MAIN
      OUTCOME FOR MEASURES: Weight, Barthel index of daily activities, several plasma
      values (albumin, C-reactive protein (CRP), homocysteine, thiamine, thiamine
      diphosphate (TDF), vitamin B6, vitamin B12, folic acid, vitamin D), bowel
      function. RESULTS: The supplement was well accepted. Thirty-five patients
      completed the intervention period (16 control group; 19 supplement group).
      Baseline daily nutrient intake was low. A statistically significant improvement
      was observed for body weight (difference between groups 2.2 kg, P=0.03), and
      homocysteine, vitamin B1, TDF, vitamin B6, vitamin B12, folate and vitamin D in
      the supplement group compared to the placebo group. No significant difference was
      observed in the Barthel index (mean difference -0.3+/-1.1 for both groups). No
      difference in occurrence of diarrhoea was observed. CONCLUSIONS: The study shows
      that nutritional supplementation is well accepted and can improve the nutritional
      status of psycho-geriatric nursing home patients. SPONSORSHIP: Numico Research
      BV.

PMID- 11960301
TI  - Fat content of the diet among pre-school children in Britain; relationship with
      food and nutrient intakes.
AB  - OBJECTIVE: To investigate the relationship between the percentage of energy from
      fat and food and nutrient intakes at 18 and 43 months of age. DESIGN: Diet was
      assessed using a 3 day unweighed food record. The children were divided into
      quartiles of fat intake as a percentage of energy (QFI), and food and nutrient
      intakes in the different QFIs were compared. SUBJECTS: A total of 1026 children
      at 18 months and 863 children at 43 months, taking part in the Avon Longitudinal
      Study of Pregnancy and Childhood, participated. RESULTS: At 18 months the mean
      (s.d.) fat intake was 31.2 (2.8) % of energy in the lowest QFI and 43.1 (2.2) %
      in the highest. Energy intake increased slightly with increasing QFI. The
      percentage of energy derived from total sugar, and in particular non-milk
      extrinsic sugar fell as QFI increased, as did the ratio of polyunsaturated to
      saturated fatty acids. Intakes of retinol equivalents and zinc increased
      significantly with increasing QFI, while intakes of iron and most water soluble
      vitamins fell. There was a particularly marked fall in vitamin C intake as fat
      intake increased, from 11.8 mg/MJ in the lowest QFI, to 6.0 mg/MJ in the highest
      (P<0.001). Consumption of whole milk increased substantially with percentage
      energy from fat, from 51 g/MJ in the lowest QFI to 116 g/MJ in the highest
      (P<0.001), while consumption of fruit and fruit juice fell. The results obtained
      at 43 months were very similar. CONCLUSIONS: The chances of a suboptimal intake
      of zinc and retinol were higher at lower fat intakes. However, intakes of the fat
      soluble vitamins E and D were unrelated to fat intake and intakes of iron and
      vitamin C fell as fat intakes increased. Some suggestions for improving diet in
      this age group have been given. SPONSOR: University of Bristol.

PMID- 11960302
TI  - Lipoprotein responses to weight loss and weight maintenance in high-risk obese
      subjects.
AB  - OBJECTIVE: To examine changes in plasma lipids and lipoproteins after 51 months
      of reduced energy intake and sustained weight loss. METHODS: One-hundred patients
      were randomized to one of two dietary interventions for 3 months (weight loss
      period). Groups A and B received an energy-restricted diet plan of 5.2-6.3 MJ/day
      but group B was further instructed to replace two of three meals with a nutrient
      fortified liquid meal replacement (MR). Upon completion of the weight loss
      period, all patients were given the same instructions regarding energy intake and
      were advised to use one MR daily. Body weight and 7 day food diaries were
      measured monthly or bimonthly and blood lipids at baseline, 3, 9 and 51 months.
      RESULTS: Of the original 100 patients 75 had completed 4 y. Of those 75, 73 had
      complete lipid records. Baseline body weights of Groups A and B were 90.7+/-14.0
      and 91.6+/-9.8 kg, respectively. The percentage change in total cholesterol
      (%DeltaTC) decreased in a linear fashion with increasing weight loss, when all
      data was combined, but did not approach statistical significance (P< or =0.26,
      r=0.02). Further regression analysis found a significant negative linear
      relationship (P< or =0.0001, r=0.69) between initial total cholesterol (TC)
      concentrations and %DeltaTC. Hence, data from 27 of the 73 completers who
      exhibited an elevated serum total cholesterol (> or =6.2 mmol/l) were isolated
      and analyzed further. Baseline TC was 6.75+/-0.64, 5.85+/-0.63 at 9 months
      (P<0.05) and 5.76+/-0.52 mmol/l at 51 months (P<0.05). Similar values for VLDL
      cholesterol were 1.33+/-0.80, 0.74+/-0.24 and 0.66+/-0.21 mmol/l by 51 months
      (P<0.05). Weight decreased by 5.2+/-5.1, 7.6+/-4.9 and 6.7+/-4.6% at 3, 9 and 51
      months, respectively. CONCLUSION: Continuous energy restriction associated with a
      clinically meaningful weight loss significantly improved the lipid profile of
      high-risk patients. Similar weight and diet changes occurring in patients with
      normal plasma cholesterol were either increased or without affect.

PMID- 11960303
TI  - Peroxisome proliferator-activated receptor-gamma agonists inhibit experimental
      allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1
      differentiation.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear
      receptor transcription factor that regulates adipocyte differentiation and
      glucose homeostasis. PPARgamma agonists are potent therapeutic agents for the
      treatment of type 2 diabetes and obesity. PPARgamma agonists also prevent
      inflammation in animal models, suggesting their use for the treatment of human
      inflammatory diseases. Experimental allergic encephalomyelitis (EAE) is a Th1
      cell-mediated inflammatory demyelinating disease model of multiple sclerosis (MS)
      and IL-12 plays a crucial role in the pathogenesis of EAE and MS. In this study
      we have examined the effect of PPARgamma agonists on the pathogenesis of EAE. In
      vivo treatment of SJL/J mice with PPARgamma agonists, 15-deoxydelta(12,14)
      prostaglandin J2 or Ciglitazone, decreased the duration and clinical severity of
      active immunization and adoptive transfer models of EAE. PPARgamma agonists
      inhibited EAE in association with a decrease in IL-12 production and
      differentiation of neural antigen-specific Th1 cells. In vitro treatment of
      activated T cells with PPARgamma agonists inhibited IL-12-induced activation of
      JAK-STAT signaling pathway and Th1 differentiation. These findings highlight the
      fact that PPARgamma agonists regulate central nervous system inflammation and
      demyelination by inhibiting IL-12 production, IL-12 signaling and Th1
      differentiation in EAE.

PMID- 11960304
TI  - Atopy in children in relation to BCG vaccination and genetic polymorphisms at
      SLC11A1 (formerly NRAMP1) and D2S1471.
AB  - The influence of the SLC11A1 (formerly NRAMP1) gene on the association between
      BCG vaccination and atopy in children was studied in 179 children, BCG vaccinated
      in infancy, and 307 children without BCG vaccination, all 3 to 8 years of age and
      with atopic heredity. DNAs were genotyped for a functional repeat polymorphism
      (designated GTn) in the promoter of SLC11A1 and a linked microsatellite D2S1471.
      Associations between genotype, atopic symptoms and allergen-specific IgE
      antibodies in relation to the BCG status of the children were assessed. Atopy in
      relation to SLC11A1 GTn-alleles was similarly distributed between the two groups.
      In BCG vaccinated children, genotype associations were observed for D2S1471 and
      atopy, with carriage of allele 5 conferring increased risk of atopy (odds ratio
      (OR) 2.6; 95% confidence interval (CI) 1.3-5.5; P = 0.01), and particularly IgE
      responses to airborne allergens (OR = 4.3; 95% CI 1.7-10.7; P = 0.002). No
      linkage disequilibrium was found between the SLC11A1 GTn repeat and the
      microsatellite D2S1471, and therefore no haplotype associations were observed for
      atopy in BCG- or non-BCG vaccinated children. Stratification by BCG vaccination
      unmasked a potential genetic risk factor for atopy in the region of the SLC11A1
      locus, and point to the importance of genotype by environment interactions in
      determining disease susceptibility.

PMID- 11960305
TI  - Distribution of TAP gene polymorphisms and extended MHC haplotypes in Mexican
      Mestizos and in Seri Indians from northwest Mexico.
AB  - The study of the genetic structure is very useful for investigating the
      biological significance of polymorphism and may provide clues to understand
      population origins. We present TAP1/TAP2 gene analysis in the Seri indians from
      Sonora, and in Mestizos from the highlands of Mexico. Thirty-two Seri and 89
      Mestizos were studied. TAP genes were typed using the ARMS-PCR technique. The
      most frequent alleles in Seri were: TAP1*0101/02, (68.8%); TAP1*02011/02012,
      (31.2%); TAP2*0201, (38.7%) and TAP2*0101, (29.0%). TAP1*0301, TAP1*0401,
      TAP2*0102 TAP2*0103 and TAP2H were absent in them. For Mestizos, the prevalent
      alleles were: TAP1*0101/02 (75.8%); TAP1*02011/12 (20.3%); TAP2*0101 (45.4%) and
      TAP2*0201 (29.3%). These results are similar to those found in Kaingang and
      Caucasians from Brazil, four Mediterranean, other Caucasians, two Oriental and
      one African group. In Seri, the extended prevalent haplotypes are typically
      Amerindian, such as TAP1*0101/2-TAP2*0201-QBP3.21-DQB1*0302-QAP*3.1-DQA1*03011
      DRB1*0407-B*3501-A*0201 (HF = 16.6%). Thirty-two extended haplotypes were found
      in Seri, although TAP contributed scarcely to diversity. Mestizos show Amerindian
      and Caucasian combinations. No difference was detected in the distribution of
      amino acids in the individual variable sites, between both groups. These findings
      are the basis for further anthropological studies and to explore the contribution
      of TAP genes to disease expression in Mexicans.

PMID- 11960306
TI  - Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African
      and South Asian populations.
AB  - Natural killer (NK) and some T cells express killer cell immunoglobulin-like
      receptors (KIRs), which interact with HLA class I expressed by target cells and
      consequently regulate cytolytic activity. The number of KIR loci can vary and so
      a range of genetic profiles is observed. We have determined the KIR genetic
      profiles from one African (n = 62) and two South Asian (n = 108, n = 78)
      populations. Several of the KIRs are present at significantly different
      frequencies between the two major ethnic groups (eg KIR2DS4 gene frequency 0.82
      African, 0.47 S Asian. Pc < 1 x 10(-6)) and this is due to uneven distribution of
      two KIR haplotype families 'A' and 'B'. All three populations described here
      displayed a greater degree of diversity of KIR genetic profiles than other
      populations investigated, which indicates further complexity of underlying
      haplotypes; in this respect we describe two individuals who appear homozygous for
      a large deletion including the previously ubiquitous 2DL4. We have also
      reanalysed three populations that we studied previously, for the presence of a
      KIR which is now known to be an indicator of the 'B' haplotype. South Asians had
      the highest overall frequencies of all KIR loci characteristic of 'B' haplotypes
      (Pc < 0.0001 to < 0.004). Furthermore, gene frequency independent deviances in
      the linkage disequilibrium were apparent between populations.

PMID- 11960307
TI  - Association study between CD30 and CD30 ligand genes and type 1 diabetes in the
      Japanese population.
AB  - CD30-CD30 ligand (CD30L) signal transduction appears to protect against
      autoimmune diabetes by preventing expansion of autoreactive T cells and
      suppressing Th1-cytokine response. The purpose of this study was to determine
      whether CD30 or CD30L genes serve as a novel susceptibility gene for type 1
      diabetes in humans. We screened CD30 and CD30L genes for polymorphisms in
      Japanese patients with type 1 diabetes and control subjects. Then, association
      studies were performed between each of the identified polymorphisms and type 1
      diabetes. Direct-sequencing analysis of the CD30 and CD30L genes revealed four
      polymorphisms: one in the CD30 gene (-201G/A from the transcription start site),
      and three in the CD30L gene [CA repeat in the promoter, 276G/A in the exon 3, 
      73T/C in the intron 3 (IVS3 -73T/C)]. Association studies revealed no association
      between the CD30 and CD30L genes and type 1 diabetes in the whole population. In
      the female and male subpopulations, however, the frequency of (CA)(9) allele of
      the CD30L gene promoter or T allele of IVS3 -73T/C polymorphism in the CD30L gene
      was slightly higher in female patients with type 1 diabetes than that in control
      females. In conclusion, we could not find significant association between CD30 or
      CD30L genes and type 1 diabetes, but (CA)(9) allele in the promotor or T allele
      of -73T/C in intron 3 in CD30L gene might play a minor role in the pathogenesis
      of type 1 diabetes, only in the Japanese female population.

PMID- 11960308
TI  - Gender and smoking-related risk reduction of periodontal disease with variant
      myeloperoxidase alleles.
AB  - Myeloperoxidase (MPO) is an oxidative enzyme expressed in polymorphonuclear
      leukocytes. It is involved in the defence against periodontal bacteria, and is
      also able to mediate inflammatory tissue destruction in periodontal disease. A
      G/A polymorphism in the promoter region of the MPO gene at position -463 has been
      assumed to exert profound effects on the expression of the enzyme. It is the aim
      of this study to evaluate whether this polymorphism may influence the risk of
      periodontal diseases. A total of 3148 subjects were randomly selected from the
      general population in the SHIP study (Study of Health in Pomerania). Periodontal
      status, health-related and socio-economic items were assessed. All subjects aged
      40-60 years (n = 1103) were included in this study, and 1083 genotyped for the
      MPO -463 G/A polymorphism by PCR and RFLP methods. The genotype frequencies
      determined were homozygous wild type G/G 65.9% (95% CI 63.5-68.6), heterozygous
      A/G 31.4% (28.8-34.4), and homozygous variant A/A 2.7% (2.0-3.8). Only female
      subjects have a significantly reduced risk of severe periodontal disease when
      bearing the variant genotypes A/G or A/A. In female subjects the reduction in
      periodontal risk was significant for non-smokers (OR = 0.48; 95% CI 0.23-0.96);
      the smoke-related increase in risk was also reduced (OR = 0.50; 95% CI 0.22
      1.10). When adjusted for age, smoking, and education the odds ratios were
      calculated as 0.52 (P = 0.01) and 0.97 (P = 0.90) for female and male subjects,
      respectively. The results of this study confirm the assumption that the MPO -463A
      allele variants are protective in the pathogenesis of periodontal diseases. This
      holds true only with women but not with men. The results are discussed with
      respect to the known influences of sexual hormones on MPO activity.

PMID- 11960309
TI  - Association between IL-4 genotype and IL-4 production in the Japanese population.
AB  - We have identified that there are only two IL-4 gene haplotypes (I and II) in the
      Japanese population. There are significant differences among three genotypes
      (I/I, I/II and II/II) in the IL-4 producing proportion of peripheral Th cells
      using intracellular cytokine detection assay. These results make it likely that
      IL-4 genotype could influence the type of immune response.

PMID- 11960310
TI  - The IDDM13 region containing the insulin-like growth factor binding protein-5
      (IGFBP5) gene on chromosome 2q33-q36 and the genetic susceptibility to rheumatoid
      arthritis.
AB  - We considered that the constitutive over-expression by cultured rheumatoid
      arthritis (RA) fibroblast-lineage synoviocytes of genes like IGFBP5 could
      indicate new candidate susceptibility genes. IGFBP5 is located in a region where
      an insulin-dependent diabetes mellitus (IDDM) susceptibility locus, IDDM13 (2q33
      q36), has been mapped. Previous evidence that non-MHC IDDM loci overlap RA
      susceptibility loci made IGFBP5 and its region an interesting candidate locus
      which was tested for linkage. Forty-nine sibships (2-4 affected siblings per
      sibship) with RA were genotyped with microsatellite markers covering an 11.2 cM
      interval in the IGFBP5/IDDM13 region. Both the two-point LOD scores and a
      'nonparametric' allele-sharing analysis revealed no evidence for linkage (max LOD
      = 0.54, P = 0.5, respectively). Adjustments for the presence of 'shared-epitope'
      alleles did not significantly change the LOD scores. These results suggest that,
      despite the involvement of the 2q33-q36 chromosomal region in another organ
      specific autoimmune disease, it is unlikely that this region harbors a RA
      susceptibility locus.

PMID- 11960311
TI  - Novel SNPs in a candidate gene, CRTH2, for allergic diseases.
AB  - Sequencing analyses of genomic DNA samples from a Chinese population identified
      four single-nucleotide polymorphisms (SNPs) of the CRTH2 gene, encoding a
      chemoattractant receptor predominantly expressed on Th2 cells and a receptor for
      prostaglandin D2 (PGD2). Two coding-region SNPs with a T to G and a C to A
      substitutions, resulting in codon changes from Phe to Val and Pro to Thr,
      respectively. Two additional SNPs were discovered in the 3' untranslated region
      (3'-UTR). These newly identified SNPs will be useful for further functional study
      of variant CRTH2 gene, and for genetic studies of asthma and other immunologic
      diseases.

PMID- 11960312
TI  - Pegylated GL67 lipoplexes retain their gene transfection activity after exposure
      to components of CF mucus.
AB  - The highly viscous secretions lining the upper airways and bronchi of cystic
      fibrosis (CF) patients may pose a significant barrier to successful gene therapy
      of the lung. In this report we examined the influence of CF mucus components
      (albumin, DNA, mucin and phospholipids) on the gene transfection activity of
      cationic DOTAP-based lipoplexes and pegylated GL67-based lipoplexes which
      previously have been used in CF clinical studies. Upon exposure of the cationic
      DOTAP:DOPE lipoplexes to either albumin, linear DNA or mucin (at concentration
      ratios expected to occur in vivo) a significant decrease in gene transfection
      activity was observed. This was primarily due to aggregation of the lipoplexes.
      However, exposure of pegylated GL67 lipoplexes to the same components did not
      affect their gene transfection activity. Indeed, it was determined that CF mucus
      components did not interact significantly with these pegylated GL67 lipoplexes.
      These results suggest that charge shielding of cationic gene carriers with pEG
      may favor their physicochemical stability in CF mucus and thereby aid in
      preserving their transfection activity.

PMID- 11960313
TI  - Development of safe and efficient novel nonviral gene transfer using ultrasound:
      enhancement of transfection efficiency of naked plasmid DNA in skeletal muscle.
AB  - Although clinical trials of stimulation of angiogenesis by transfection of
      angiogenic growth factors using naked plasmid DNA or adenoviral vector have been
      successful, there are still unresolved problems for human gene therapy such as
      low transfection efficiency and safety. From this viewpoint, it is necessary to
      develop safe and efficient novel nonviral gene transfer methods. As therapeutic
      ultrasound induces cell membrane permeabilization, ultrasound irradiation might
      increase the transfection efficiency of naked plasmid DNA into skeletal muscle.
      Thus, we examined the transfection efficiency of naked plasmid DNA using
      ultrasound irradiation with echo contrast microbubble (Optison) in vitro and in
      vivo experiments. First, we examined the feasibility of ultrasound-mediated
      transfection of naked plasmid DNA into skeletal muscle cells. Luciferase plasmid
      mixed with or without Optison was transfected into cultured human skeletal muscle
      cells using ultrasound (1 MHz; 0.4 W(2)) for 30 s. Interestingly, luciferase
      activity was markedly increased in cells treated with Optison, while little
      luciferase activity could be detected without Optison (P < 0.01). Electron
      microscopy demonstrated the transient formation of holes (less than 5 microM) in
      the cell surface, which could possibly explain the rapid migration of the
      transgene into the cells. Next, we studied the in vivo transfection efficiency of
      naked plasmid DNA using ultrasound with Optison into skeletal muscle. Two days
      after transfection, luciferase activity in skeletal muscle transfected with
      Optison using ultrasound was significantly increased about 10-fold as compared
      with plasmid alone. Successful transfection was also confirmed by beta
      galactosidase staining. Finally, we examined the feasibility of therapeutic
      angiogenesis using naked hepatocyte growth factor (HGF) plasmid in a rabbit
      ischemia model using the ultrasound-Optison method. Five weeks after
      transfection, the angiographic score and the number of capillary density in
      rabbits transfected with Optison using ultrasound was significantly increased as
      compared with HGF plasmid alone (P < 0.01), accompanied by a significant increase
      in blood flow and blood pressure ratio (P < 0.01). Overall, the ultrasound
      transfection method with Optison enhanced the transfection efficiency of naked
      plasmid DNA in vivo as well as in vitro. Transfection of HGF plasmid by the
      ultrasound-Optison method could be useful for safe clinical gene therapy to treat
      peripheral arterial disease without a viral vector system.

PMID- 11960314
TI  - Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes
      functional recovery in a rat model of Parkinson's disease.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a strong candidate agent in
      the neuroprotective treatment of Parkinson's disease (PD). We investigated
      whether adeno-associated viral (AAV) vector-mediated delivery of a GDNF gene in a
      delayed manner could prevent progressive degeneration of dopaminergic (DA)
      neurons, while preserving a functional nigrostriatal pathway. Four weeks after a
      unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), rats received
      injection of AAV vectors expressing GDNF tagged with FLAG peptide (AAV-GDNFflag)
      or beta-galactosidase (AAV-LacZ) into the lesioned striatum. Immunostaining for
      FLAG demonstrated retrograde transport of GDNFflag to the substantia nigra (SN).
      The density of tyrosine hydroxylase (TH)-positive DA fibers in the striatum and
      the number of TH-positive or cholera toxin subunit B (CTB, neuronal tracer)
      labeled neurons in the SN were significantly greater in the AAV-GDNFflag group
      than in the AAV-LacZ group. Dopamine levels and those of its metabolites in the
      striatum were remarkably higher in the AAV-GDNFflag group compared with the
      control group. Consistent with anatomical and biochemical changes, significant
      behavioral recovery was observed from 4-20 weeks following AAV-GDNFflag
      injection. These data indicate that a delayed delivery of GDNF gene using AAV
      vector is efficacious even 4 weeks after the onset of progressive degeneration in
      a rat model of PD.

PMID- 11960315
TI  - Regression of tumors by IFN-alpha electroporation gene therapy and analysis of
      the responsible genes by cDNA array.
AB  - The key to success with nonviral gene therapy as a treatment for cancer is to
      discover effective therapeutic genes and gene delivery methods and to understand
      how tumors are eradicated. We discovered that electroporation of IFN-alpha DNA
      into tumors in the SCCVII tumor-bearing mice led to tumor eradication in 50% of
      the mice and a more than two-fold increase in survival time when compared with
      controls (P = 0.0012). Analyses using cDNA array and Northern blot indicated that
      the genes responsible for the therapeutic effect of electro-IFN-alpha gene
      therapy included IRF-7, Granzyme A, Granzyme C, Gjb2, Krt14, Mig, IP-10 and MCP3.
      Because most of these genes have been known to either inhibit angiogenesis (Mig,
      IP-10), inhibit tumor growth (Gjb2, MCP3), kill tumor cells (Granzyme A and C),
      or induce expression of antitumor gene (IRF-7), they may become promising
      therapeutic gene candidates for a combination gene therapy approach to cancer
      treatment.

PMID- 11960317
TI  - Polyion complex micelles as vectors in gene therapy--pharmacokinetics and in vivo
      gene transfer.
AB  - To establish non-viral gene delivery systems for intravenous administration,
      complexes of DNA and block copolymer consisting of poly-L-lysine and
      poly(ethylene glycol) were tested in in vivo turnover studies. The polyion
      complex micelles have self-assembling core-shell structures, yielding spherical
      nano-particles with small absolute values of zeta-potential. Southern blot
      analysis showed that supercoiled DNA was observed for 30 min and open circular or
      linear DNA was seen for 3 h after intravenous administration of PIC micelles
      having the charge ratios of 1:4 and PLL length of 48 mer. The PIC micelles with
      shorter PLL length showed lower stability in the blood stream suggesting that DNA
      is able to persist as an intact molecule in the blood stream using this system.
      Though having no ligands, PIC micelles with charge ratios of 1:2 and 1:4
      transfected efficiently into HepG2 cells. Preincubation with free copolymer
      inhibited expression of the reporter gene, suggesting that adsorption of block
      copolymer to the cell surface blocked the interaction site of the PIC micelles.
      When the PIC micelles were injected via supramesenteric vein, expression of the
      gene was observed only in the liver and was sustained for 3 days. It was
      suggested that this gene delivery system is intrinsically efficient.

PMID- 11960316
TI  - The potential for efficacy of the modified (ICP 34.5(-)) herpes simplex virus
      HSV1716 following intratumoural injection into human malignant glioma: a proof of
      principle study.
AB  - We have previously demonstrated the safety of intratumoural administration of the
      selectively replication-competent herpes simplex virus mutant HSV1716 in patients
      with high-grade glioma (HGG). Here we show its potential for efficacy by
      demonstrating that the virus survives and replicates when injected into the
      tumours of patients. Since HSV replication is a cytolytic process it must result
      in tumour cell killing. Twelve patients with biopsy-verified HGG received an
      intratumoural injection of 10(5) plaque-forming units (p.f.u.) of HSV1716. Four
      to 9 days after inoculation, tumours were removed and assayed for evidence of
      viral replication. In two patients, HSV1716, in excess of the input dose was
      recovered from the injection site. HSV DNA was detected by PCR at the sites of
      inoculation in 10 patients and at distal tumour sites in four. HSV-specific
      antigen was detected in tumour tissue from two patients. In five patients an
      immunological response to HSV1716, as detected by changes in levels of IgG and
      IgM, was demonstrated. This study demonstrates that HSV1716 replicates in HGG
      without causing toxicity in both HSV-seropositive and -seronegative patients.

PMID- 11960318
TI  - Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in
      vivo transient focal cerebral ischemia in an animal model.
AB  - Acute cerebral ischemia causes hypoxic neuronal cell death by necrosis and
      apoptosis. Expression of anti-apoptotic transgenes in ischemic brain may provide
      a useful therapeutic strategy for alleviation of postischemic damage. The present
      study investigates liposome-mediated transfer of the human bcl-2 protein in a rat
      model of focal transient ischemia due to middle cerebral artery (MCA) occlusion.
      Two different types of plasmid vectors were used for bcl-2 expression: one driven
      by the constitutive cytomegalovirus promoter (pCMV) and another based on the
      hypoxia-inducible human vascular endothelial growth factor promoter (pHRE).
      Cationic liposome/plasmid DNA complexes (lipoplexes) were injected directly into
      the cerebrospinal fluid (CSF) of rats immediately after MCA occlusion. The brains
      of treated and control animals were analyzed 48 h later. Infarct volumes and
      numbers of apoptotic cells were quantified. Occlusion of the MCA resulted in
      ipsilateral cerebral infarcts in all study animals. Transfer of the bcl-2 gene
      resulted in high level widespread protein expression in the case of the pCMV-bcl2
      plasmid, while animals treated with the pHRE-bcl2 vector showed lower expression
      levels of bcl2 which were in addition limited to the ischemic area. Treatment
      with pCMV-bcl2, but not with pHRE-bcl2, was able to significantly reduce the
      infarct volume, which was 109 +/- 8 mm(3) for pCMV-bcl2, 152 +/- 29 mm(3) for
      pHRE-bcl2, and 155 +/- 18 mm(3) for control animals. Animals transfected with
      either vector showed a significant reduction in numbers of apoptotic cells in the
      infarct and penumbra area compared with controls. There were no short-term
      neurological side-effects of the CSF injection of lipoplexes or of bcl-2
      expression. In conclusion, the hypoxia-inducible bcl-2 expression mediated by
      intrathecal lipoplexes may represent a novel, biologically safe and lesion
      selective therapeutic approach for neuroprotection after acute cerebral ischemia.
      DOI: 10.1038/sj/gt/3301676

PMID- 11960319
TI  - Spotlight on molecular targeted therapy: introduction.

PMID- 11960320
TI  - The proteasome: a novel target for cancer chemotherapy.
AB  - The ubiquitin-proteasome system is an important regulator of cell growth and
      apoptosis. The potential of specific proteasome inhibitors to act as novel anti
      cancer agents is currently under intensive investigation. Several proteasome
      inhibitors exert anti-tumour activity in vivo and potently induce apoptosis in
      tumour cells in vitro, including those resistant to conventional chemotherapeutic
      agents. By inhibiting NF-kappaB transcriptional activity, proteasome inhibitors
      may also prevent angiogenesis and metastasis in vivo and further increase the
      sensitivity of cancer cells to apoptosis. Proteasome inhibitors also exhibit some
      level of selective cytotoxicity to cancer cells by preferentially inducing
      apoptosis in proliferating or transformed cells or by overcoming deficiencies in
      growth-inhibitory or pro-apoptotic molecules. High expression of oncogene
      products like c-Myc also makes cancer cells more susceptible to proteasome
      inhibitor-induced apoptosis. The induction of apoptosis by proteasome inhibitors
      varies between cell types but often occurs following an initial accumulation of
      short-lived proteins such as p53, p27, pro-apoptotic Bcl-2 family members or
      activation of the stress kinase JNK. These initial events often result in a
      perturbation of mitochondria with concomitant release of cytochrome c and
      activation of the Apaf-1 containing apoptosome complex. This results in
      activation of the apical caspase-9 followed by activation of effector caspases-3
      and -7, which are responsible for the biochemical and morphological changes
      associated with apoptosis.

PMID- 11960321
TI  - MCL1 provides a window on the role of the BCL2 family in cell proliferation,
      differentiation and tumorigenesis.
AB  - The MCL1 gene (myeloid cell leukemia-1) was discovered serendipitously about a
      decade ago and proved to be a member of the emerging BCL2 gene family. Ongoing
      studies of this gene provide an interesting perspective on the role of the BCL2
      family in transitions in cell phenotype. Specifically, gene products that
      influence cell viability as a major effect (eg MCL1, BCL2 and other family
      members) can act as key determinants in cell proliferation, differentiation and
      tumorigenesis. Although they do not have a direct role in
      proliferation/differentiation programs, these genes can either permit these
      programs to proceed or prevent them. Through such effects, the BCL2 family
      regulates the normal flow of cells through cycles of proliferation and along
      various pathways of differentiation. A model is presented suggesting that this is
      accomplished by sustaining or inhibiting viability at critical points in the cell
      lifecycle. These critical points represent windows of time during which cell fate
      transitions are effected. They can also be visualized as windows that open or
      close to promote or prevent continued progression along various cell fate
      pathways. The pattern of BCL2 family expression at these points allows for the
      proliferation differentiation, and continued viability of cell types that are
      needed, while aborting these processes for cells that are overabundant or no
      longer needed. The combined action of the various family members can therefore
      control the fate of cells, tissues and even the organism. This mechanism
      involving apoptosis-related genes is readily executable, and is poised to respond
      to external signals through the differential regulation of BCL2 family members.
      As such, it plays an important role in the maintenance of tissue homeostasis and
      function. Alterations that affect the BCL2 family impair the capacity to control
      the flow of cells through these critical points, and thereby 'leave the window
      open' for cell immortalization and cancer. Targeting this family may thus provide
      a means of inhibiting cancer development and inducing apoptosis in tumor cells.

PMID- 11960322
TI  - Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs.
AB  - Geldanamycin (GA), herbimycin A and radicicol bind heat-shock protein-90 (Hsp90)
      and destabilize its client proteins including v-Src, Bcr-Abl, Raf-1, ErbB2, some
      growth factor receptors and steroid receptors. Thus, Hsp90-active agents induce
      ubiquitination and proteasomal degradation of numerous oncoproteins. Depending on
      the cellular context, HSP90-active agents cause growth arrest, differentiation
      and apoptosis, or can prevent apoptosis. HSP-active agents are undergoing
      clinical trials. Like targets of most chemotherapeutics, Hsp90 is not a cancer
      specific protein. By attacking a nonspecific target, HSP-90-active compounds
      still may preferentially kill certain tumor cells. How can this be achieved? How
      can therapeutic potentials be exploited? This article starts the discussion.

PMID- 11960323
TI  - Classical and novel retinoids: their targets in cancer therapy.
AB  - Retinoids are important mediators of cellular growth and differentiation.
      Retinoids modulate the growth of both normal and malignant cells through their
      binding to retinoid nuclear receptors and their subsequent activation. While
      retinoids have demonstrated therapeutic efficacy in the treatment of acute
      promyelocytic leukemia, their spectrum of activity remains limited. Other agents
      such as histone deacetylase inhibitors may significantly increase retinoid
      activity in a number of malignant cell types. The novel retinoids N-(4
      hydroxyphenyl) retinamide (4-HPR) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2
      naphthalene carboxylic acid (CD437; AHPN) induce apoptosis in a wide variety of
      malignant cells. Their mechanism(s) of action remain unclear, although a number
      of potential targets have been identified. Whether the retinoid receptors are
      involved in 4-HPR and CD473/AHPN mediated apoptosis remains unclear. Both 4-HPR
      and CD437/AHPN display significant potential as therapeutic agents in the
      treatment of a number of premalignant and malignant conditions.

PMID- 11960324
TI  - Large-scale gene expression analysis in molecular target discovery.
AB  - The evolution of simple arrays consisting of a few genes to ones composed of
      thousands of genes and/or ESTs has allowed investigators unprecedented views of
      the molecular mechanisms within cells. Due to the enormous quantities of
      information derived from microarray analysis, new types of problems have
      surfaced, such as where to store all of the data. The ability to solve database
      or statistical problems has required the bench biologist to collaborate with
      database developers, software designers and statisticians to determine solutions
      for storage, analysis and interpretation of microarray data. The collaborative
      effort between these extremely diverse disciplines has led to the development of
      creative database query and gene expression analysis tools, producing significant
      reductions in the time required by researchers to filter through the datasets and
      discover the key processes perturbed by the diseases of interest. Both
      unsupervised and supervised analysis methods have been applied to gene expression
      data leading to the discovery of novel therapeutic targets and diagnostic
      markers. Furthermore, tumor classification based on their respective molecular
      fingerprints has led to the classification of cancer subtypes and the discovery
      of novel molecular taxonomies that may eventually lead to improved patient
      stratification and superior therapeutic strategies.

PMID- 11960325
TI  - Identification of novel targets for cancer therapy using expression proteomics.
AB  - Although most drugs target proteins, the proteome has remained largely untapped
      for the discovery of drug targets. The sequencing of the human genome has had a
      tremendous impact on proteomics and has provided a framework for protein
      identification. There is currently substantial interest in implementing
      proteomics platforms for drug target discovery. Although the field is still in
      the early stages, current proteomic tools include a variety of technologies that
      could be implemented for large-scale protein expression analysis of cells and
      tissues, leading to discovery of novel drug targets. Proteomics uniquely allows
      delineation of global changes in protein expression patterns resulting from
      transcriptional and post-transcriptional control, post-translational
      modifications and shifts in proteins between different cellular compartments.
      Some of the current technologies for proteome profiling and the application of
      proteomics to the analysis of leukemias by our group are reviewed.

PMID- 11960326
TI  - The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic
      intervention in leukemia.
AB  - The Raf/MEK/ERK (MAPK) signal transduction cascade is a vital mediator of a
      number of cellular fates including growth, proliferation and survival, among
      others. The focus of this review centers on the MAPK signal transduction pathway,
      its mechanisms of activation, downstream mediators of signaling, and the
      transcription factors that ultimately alter gene expression. Furthermore,
      negative regulators of this cascade, including phosphatases, are discussed with
      an emphasis placed upon chemotherapeutic intervention at various points along the
      pathway. In addition, mounting evidence suggests that the PI3K/Akt pathway may
      play a role in the effects elicited via MAPK signaling; as such, potential
      interactions and their possible cellular ramifications are discussed.

PMID- 11960327
TI  - HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs
      as triggers of tumor-specific apoptosis.
AB  - The statin family of drugs target HMG-CoA reductase, the rate-limiting enzyme of
      the mevalonate pathway, and have been used successfully in the treatment of
      hypercholesterolemia for the past 15 years. Experimental evidence suggests this
      key biochemical pathway holds an important role in the carcinogenic process.
      Moreover, statin administration in vivo can provide an oncoprotective effect.
      Indeed, in vitro studies have shown the statins can trigger cells of certain
      tumor types, such as acute myelogenous leukemia, to undergo apoptosis in a
      sensitive and specific manner. Mechanistic studies show bcl-2 expression is down
      regulated in transformed cells undergoing apoptosis in response to statin
      exposure. In addition, the apoptotic response is in part due to the depletion of
      the downstream product geranylgeranyl pyrophosphate, but not farnesyl
      pyrophosphate or other products of the mevalonate pathway including cholesterol.
      Clinically, preliminary phase I clinical trials have shown the achievable plasma
      concentration corresponds to the dose range that can trigger apoptosis of tumor
      types in vitro. Moreover, little toxicity was evident in vivo even at high
      concentrations. Clearly, additional clinical trials are warranted to further
      assess the safety and efficacy of statins as novel and immediately available anti
      cancer agents. In this article, the experimental evidence supporting a role for
      the statin family of drugs to this new application will be reviewed.

PMID- 11960328
TI  - Developmental therapeutics program at the NCI: molecular target and drug
      discovery process.
AB  - As the drug discovery and developmental arm of the National Cancer Institute
      (NCI), the Developmental Therapeutics Program (DTP) plans, conducts and
      facilitates development of therapeutic agents for cancer and AIDS. DTP's goal is
      to turn 'molecules into medicine for the public health'. Areas of support by DTP
      are discovery, development and pathways to development for the intramural and the
      extramural community. The Developmental Therapeutics Program (DTP) operates a
      repository of synthetic and pure natural products, which are evaluated as
      potential anticancer agents. The repository derives from a historical database of
      greater than 600 000 compounds, which have been supplied to DTP from a variety of
      sources worldwide. The in vitro anti-cancer drug cell line screen established at
      DTP is unique in several respects. It has changed the NCI emphasis from a
      compound-oriented drug discovery effort to a disease-panel oriented exercise,
      emphasized human tumor cells derived from solid tumors, developed a high volume
      screening method that can adapt to processing of numerous chemical agents or
      natural source-derived extracts, that has minimized the use of animals, and saved
      on the amount of material required for the initial screening. The hollow fiber
      assay created at the DTP has demonstrated the ability to provide quantitative
      initial indices of in vivo drug efficacy, with minimum expenditures of time and
      materials and is currently being utilized as the initial in vivo experience for
      agents found to have reproducible activity in the in vitroanticancer drug screen.
      Drugs showing activity with unique mechanisms of actions are being further
      developed for treatment of hematopoietic neoplasms, prominent examples being
      flavopiridol, UCN-01 and depsipeptide among others.

PMID- 11960329
TI  - Myeloid differentiation (MyD)/growth arrest DNA damage (GADD) genes in tumor
      suppression, immunity and inflammation.
AB  - Myeloid differentiation (MyD) primary response and growth arrest DNA damage
      (Gadd) genes comprise a set of overlapping genes, including known (IRF-1, EGR-1,
      Jun) and novel (MyD88, Gadd45alpha, MyD118/Gadd45beta, GADD45gamma, MyD116/
      Gadd34) genes, that have been cloned by virtue of being co-ordinately induced
      upon the onset of terminal myeloid differentiation and following exposure of
      cells to stress stimuli. In recent years it has become evident that MyD/Gadd play
      a role in blood cell development, where they function as positive regulators of
      terminal differentiation, lineage-specific blood cell development and control of
      blood cell homeostasis, including growth inhibition and apoptosis. MyD/Gadd are
      also involved in inflammatory responses to invading micro-organisms, and response
      to environmental stress and physiological stress, such as hypoxia, which results
      in ischemic tissue damage. An intricate network of interactions among MyD/GADD
      genes and gene products appears to control their diverse functions. Deregulated
      growth, increased cell survival, compromised differentiation and deficiencies in
      DNA repair are hallmarks of malignancy and its progression. Thus, the role
      MyD/Gadd play in negative growth control, including cell cycle arrest and
      apoptosis, and in DNA repair, make them attractive molecular targets for tumor
      suppression. The role MyD/Gadd play in innate immunity and host response to
      hypoxia also make these genes and gene products attractive molecular targets to
      treat immunity and inflammation disorders, such as septic shock and ischemic
      tissue damage.

PMID- 11960330
TI  - Toward a new paradigm of cell plasticity.
AB  - The standard paradigm of embryologic development and adult tissue reconstitution
      posits unidirectional, hierarchical lineages. The presumed mechanisms underlying
      these differentiative pathways are gene restrictions, such as methylation and
      heterochromatin formation, which are commonly described as irreversible. However,
      recent discoveries regarding multi-organ stem cells demonstrate that 'true
      plasticity' exists, with cells of one organ turning into cells of other organs,
      including differentiative transformations that cross barriers between tissues
      derived from different primitive germ layers. These findings, along with earlier
      experiments into heterokaryon formation and longstanding recognition of reactive
      and neoplastic lesions in humans and animals, suggest that lineage pathways are
      not, in fact, unidirectional. Moreover, physiologic mechanisms of reversal of
      gene restrictions have been recognized. Therefore, in response to these
      observations, we suggest a new paradigm of cell plasticity, elucidating three
      guiding principles of 'genomic completeness', 'uncertainty of cell
      characterization', and 'stochastic nature of cell origins and fates'. These
      principles imply a change in the way data can be interpreted and could alter
      subsequent hypothesis formation. This new paradigm will hopefully lead us forward
      to a more flexible and creative exploration of the potential of adult vertebrate
      cells.

PMID- 11960332
TI  - Unique molecular and cellular features of acute myelogenous leukemia stem cells.
AB  - It is well known in the field of acute myelogenous leukemia (AML) that many
      different translocations and genetic aberrancies are found with the various forms
      of the disease. Indeed, specific translocations are often associated with disease
      subtypes that manifest themselves through the accumulation of immature myeloid
      cells at varying stages of differentiation. Moreover, the differentiation state
      of myeloid blast populations has been utilized as a means of categorizing
      different AML subtypes (French, American, British, or FAB classification system).
      Thus, the notion that AML is a family of related but distinct diseases is a
      common view. Interestingly, however, studies in recent years that have formalized
      the concept of a leukemic stem cell (LSC) have also begun to define shared
      developmental, cellular and molecular features amongst the malignant stem cells
      that give rise to different AML subtypes. Moreover, some of these conserved
      features appear to be unique to the leukemia stem/progenitor cell population, and
      are not found in normal hematopoietic stem cells (HSCs). This article will
      summarize data emerging from the study of LSCs and suggest how distinct molecular
      and cellular characteristics of the LSC population may provide new opportunities
      for AML therapy.

PMID- 11960331
TI  - Elucidating critical mechanisms of deregulated stem cell turnover in the chronic
      phase of chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) has been studied intensively for many years; yet
      its treatment remains problematic and its biology remains elusive. In chronic
      phase, the leukemic clone appears to be maintained by a small number of BCR-ABL
      positive hematopoietic stem cells that differentiate normally and amplify slowly.
      In contrast, as these cells enter the intermediate stages of lineage restriction,
      their progeny are selectively expanded and generate an enlarged pool of
      neoplastic progenitors. Recent analyses of purified subsets of primitive CML
      cells have provided a coherent explanation for this dichotomous behavior of BCR
      ABL-positive stem and progenitor cells based on the discovery of an unusual
      autocrine IL-3/G-CSF mechanism activated in them. This only partially counteracts
      in vivosignals that maintain normal stem cells in a quiescent state but, when
      active in CML stem cells, promotes their differentiation in favor of their self
      renewal. In more differentiated CML progenitors, the same mechanism has a more
      potent mitogenic effect which is then extinguished when the cells enter the
      terminal stages of differentiation. Thus, further expansion of the clone is
      limited until inevitably additional mutations are acquired that further distort
      or override the regulatory mechanisms still operative in the chronic phase.

PMID- 11960333
TI  - Development of gene therapy for hematopoietic stem cells using lentiviral
      vectors.
AB  - Lentiviral vectors are promising tools for the development of gene therapy since
      they can transduce both quiescent and dividing target cells. Lentiviral vectors
      may be particularly promising gene delivery tools for hematopoietic stem cells
      since these target cells tend to be quiescent and are therefore difficult target
      cells for vectors that require dividing targets. Human hematopoietic stem cells
      that can repopulate NOD/SCID mice have been efficiently transduced using HIV-1
      based lentiviral vectors and similar vectors can also transduce murine
      hematopoietic stem cells. HIV-1 vectors that contain strong general promoters can
      generate high levels of transgene expression and very high expression levels can
      be generated in erythroid cells in vivo using beta-globin regulatory sequences to
      control the expression of the transgene. Current lentiviral vectors have a
      similar level of biosafety as oncoretroviral vectors and can therefore
      theoretically be used in clinical gene therapy protocols. Future challenges
      include the generation of lentiviral vectors that can express more than one
      transgene at high levels and the generation of safe permanent packaging cells for
      practical use in clinical gene therapy trials.

PMID- 11960334
TI  - STI-571 must select for drug-resistant cells but 'no cell breathes fire out of
      its nostrils like a dragon'.
AB  - Seemingly disappointing, the Bcr-Abl kinase inhibitor STI-571 shares an
      'unfortunate' characteristic with conventional cancer drugs: the development of
      drug resistance. I argue that the resistance must develop even faster to STI-571
      than to conventional drugs, because STI-571 is so effective. This is predictable,
      but is it inevitable? And how do mechanisms of resistance in relapse depend on a
      degree of remission. In addition to mutation rate and number of tumor cells, one
      additional factor determines relapse vs. 'extinction' of the leukemia cell
      population.

PMID- 11960335
TI  - Results of a phase II trial of a combination of oral cytarabine ocfosfate (YNK01)
      and interferon alpha-2b for the treatment of chronic myelogenous leukemia
      patients in chronic phase.
AB  - Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is
      resistant to systemic deamination after oral administration. Following initial
      studies indicating significant anti-tumour activity of YNK01 a phase II trial was
      initiated in order to assess the tolerability and efficacy of a combination of
      this agent with interferon alpha-2b (IFN-alpha2b) in recently diagnosed chronic
      phase CML patients (n = 98). The treatment was subdivided into cycles consisting
      of 4 weeks of continuous administration of IFN-alpha-2b (3 MU/m(2)/day 1st week
      and then 5 MU/m(2)/day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the
      end of each cycle the dose of YNK01 was adjusted according to the blood count
      observed during the previous 4 weeks. The median time from diagnosis to inclusion
      in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients
      (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of
      98 patients, two achieved a complete cytogenetic response, 14 a partial response
      (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19
      patients were not evaluable for cytogenetic response. During the trial, 20
      patients progressed to accelerated (6) or blastic phases (14). The median time to
      progression was 15 months (range 2-38 months). At 3 years the overall survival
      was 79% (95% CI, 70-88). Although the complete hematological response rate
      compared favorably with the 40% response rate previously obtained with the
      subcutaneous formulation of Ara-c, the cytogenetic response rate was less than
      expected. Most of the patients experienced side-effects and all permanently
      stopped YNK01. Although the combination seems attractive the initial dose of 600
      mg per day is probably too high and should be reconsidered in further trials.

PMID- 11960336
TI  - Less intense conditioning with fludarabine, cyclophosphamide, idarubicin and
      etoposide (FCIE) followed by allogeneic unselected peripheral blood stem cell
      transplantation in elderly patients with leukemia.
AB  - The objective of this study was to assess toxicity and feasibility of achieving
      engraftment of allogeneic blood progenitor cells following nonmyeloablative
      conditioning according to the FCIE protocol (fludarabine 25 mg/m(2)/day, days -7
      to -3; cyclophosphamide 200 mg/m(2)/day, days -7 to -3; idarubicin 12
      mg/m(2)/day, days -7 to -5; etoposide 250 mg/m(2)/day, days -4 to -3) in elderly
      patients with leukemia. Eleven patients were included in the study: six patients
      with acute myeloid leukemia (AML) in complete remission (CR); three patients with
      refractory or relapsed AML; one patient with chronic myeloid leukemia; one
      patient with acute lymphoblastic leukemia. The median age of the patients was 62
      years. All patients received blood progenitor cells from an HLA-identical sibling
      with 8.8 x 10(6) CD34(+) cells/kg (median; range 4.7 to 26.2 x 10(6)/kg) and 5.5
      x 10(8) CD3(+)cells/kg (median; range 4.5 to 7.9 x 10(8)/kg). Graft-versus-host
      disease (GVHD) prophylaxis consisted of cyclosporine and three courses of
      methotrexate. The median duration of white blood cell counts <1 x 10(9)/l was 17
      days and of platelet counts <50 x 10(9)/l 20 days. In two patients acute GVHD
      grade I occurred. Nine of 10 patients analyzed developed mixed chimerism. Of
      seven patients transplanted in CR, three remained in CR 19 to 31 months after
      transplantation. Three patients with refractory leukemia did not achieve CR,
      while the patient with relapsed AML achieved a 3rd CR. After a median follow-up
      time of 22 months, chronic GVHD was mild and limited. The data from this pilot
      study in elderly patients with leukemia show that the combination of primarily
      immunosuppressive (FC) and antileukemic (IE) drugs for nonmyeloablative
      conditioning has moderate nonhematological toxicity and allows engraftment of
      allogeneic blood progenitor cells.

PMID- 11960337
TI  - Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy
      with stem cell transplantation induces a high rate of complete response and
      improves event-free survival in mantle cell lymphoma: a prospective study.
AB  - Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor
      prognosis. We have conducted a prospective study in patients with MCL to evaluate
      a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if
      CHOP failed to induce complete remission. Responding patients then proceeded to
      an intensification therapy with autologous peripheral blood stem cell
      transplantation (APBSCT). Twenty-eight consecutive patients with newly diagnosed
      aggressive MCL were included. After four cycles of CHOP regimen, two complete
      responses (CR) were obtained (7%) and 14 (50%), five (18%) and seven (25%)
      patients achieved partial (PR), minor (MR) and no response, respectively (one
      patient died from septic complications during CHOP induction). The two patients
      in CR after CHOP underwent intensification with TBI, high-dose cyclophosphamide
      etoposide and APBSCT. The other twenty-five patients received DHAP and in this
      group a response rate of 92% (21 CR (84%), two PR (8%)) was observed. Two
      patients had progressive disease. The twenty-three responding patients received
      high-dose therapy (TAM8 regimen: TBI-cytarabine-melphalan) followed by APBSCT.
      One of the two partial responding patients achieved CR after TAM8. After a median
      follow-up of 47.6 months (range, 14-70), seven patients have relapsed. Our data
      confirm that: (1) CHOP regimen induces a low CR rate in MCL; (2) CHOP plus DHAP
      appears to be much more efficient and allows a large proportion of patients to
      proceed to high-dose therapy in CR; (3) consolidation therapy including TBI and
      high-dose Arac-C followed by APBSCT may improve event-free survival.

PMID- 11960338
TI  - Long-term follow-up of short intensive multiagent chemotherapy without high-dose
      methotrexate ('Orange') in children with advanced non-lymphoblastic non-Hodgkin's
      lymphoma: a children's cancer group report.
AB  - Despite prolonged therapy (18 months), children with advanced non-lymphoblastic,
      non-Hodgkin's lymphoma (NHL) treated on previous Children's Cancer Group (CCG)
      trials achieved less than a 60% 5-year event-free survival (EFS). In this study
      we piloted a shorter but more intensive protocol ('Orange') to determine the
      feasibility, safety, and efficacy of this alternative treatment approach. Thirty
      nine children received a CHOP-based induction, etoposide/ifosfamide
      consolidation, DECAL (dexamethasone, etoposide, cisplatin, cytosine arabinoside
      (Ara-C) and L-asparaginase) intensification, and either one or two similar but
      less intense maintenance courses. Patients were stratified to standard-risk (5
      months) vs high-risk (7 months) treatment. High risk was defined as either bone
      marrow disease, CNS disease, mediastinal mass > or = one-third thoracic diameter
      at T5 and/or LDH > or =2 times institutional upper limits of normal. All other
      patients were considered to be standard risk. Results were compared with the
      previous CCG NHL study (CCG-503). Sixteen and 23 patients were considered
      standard- vs. high-risk, respectively. The 5-year EFS and overall survival (OS)
      were 77 +/- 7% and 80 +/- 7%, respectively. The 5-year EFS and OS were
      significantly better in the standard- vs. high-risk subgroups (100% vs. 61 +/-
      11%) (P < 0.003) and (100% vs. 65 +/- 11%) (P < 0.01), respectively. Lactate
      dehydrogenase (LDH) > or =2 x normal (NL) was associated with significantly
      poorer outcomes (LDH > or =2 x NL vs. <2 x NL) (5-year EFS: 55 +/- 12% vs. 100%)
      (P < 0.0004). This CCG hybrid regimen, 'Orange', of short and more intensive
      therapy resulted in a significant improvement in outcomes compared with the
      previous CCG trial of more prolonged but less intense therapy. This regimen that
      deletes high-dose methotrexate, if confirmed in a larger trial, could be
      considered as an alternative treatment approach in children without high tumor
      burdens (LDH <2 x NL) and Murphy stage III disease.

PMID- 11960339
TI  - Prognostic variables in newly diagnosed children and adolescents with acute
      myeloid leukemia: Children's Cancer Group Study 213.
AB  - The objective of this study was to identify biologic parameters that were
      associated with either exceptionally good or poor outcome in childhood acute
      myeloid leukemia (AML). Among the children with AML who entered Children's Cancer
      Group trial 213, 498 patients without Down syndrome or acute promyelocytic
      leukemia (APL) comprise the basis for this report. Univariate comparisons of the
      proportion of patients attaining complete remission after induction (CR) indicate
      that, at diagnosis, male gender, low platelet count (< or =20 000/microl),
      hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB)
      category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of
      induction, and +8 are associated with lower CR rates, while abnormal 16 is
      associated with a higher CR rate. Multivariate analysis suggests high platelet
      count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM
      blast percentage, and abnormal 16 are independent prognostic factors associated
      with better CR. Univariate analysis demonstrated a significant favorable
      relationship between platelet count at diagnosis (>20 000/microl), absence of
      hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with
      overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage,
      and abnormal 16 were determined to be independent prognostic factors associated
      with better survival.

PMID- 11960340
TI  - Plant stress hormones suppress the proliferation and induce apoptosis in human
      cancer cells.
AB  - Cellular stressors induce various outcomes including inhibition of cell
      proliferation and cell death. Sodium salicylate (SA), a plant stress hormone, can
      suppress the proliferation or cause apoptosis in certain mammalian cancer cells.
      Plant stress hormones are activators of cellular responses, including cell death,
      to diverse stress situations in plants. Thus, we hypothesized that plant stress
      hormones share the ability to adversely affect cancer cells. We found that the
      plant stress hormone SA suppressed proliferation of lymphoblastic leukemia,
      prostate, breast and melanoma human cancer cells. Jasmonic acid (JA), a plant
      stress hormone belonging to the Jasmonate family, induced death in lymphoblastic
      leukemia cells and caused suppression of cell proliferation in the other human
      cancer cells mentioned above. Another member of the Jasmonate family, methyl
      jasmonate (MJ), induced death in each of the cell lines. Plant stress hormones
      did not affect normal human lymphocytes, in contrast to their strong effect on
      lymphoblastic leukemia cells. JA and MJ caused apoptotic death, as determined by
      characteristic nuclear morphology, flow cytometric DNA profile and elevation of
      caspase-3 activity. Finally, mice bearing EL-4 lymphoma and treated with MJ,
      survived for significantly (P = 0.00953) longer periods of time than untreated
      mice. These findings suggest that plant stress hormones may potentially be a
      novel class of anti-cancer drugs.

PMID- 11960342
TI  - Primary myelodysplasia occurring in adults under 50 years old: a
      clinicopathologic study of 52 patients.
AB  - Although myelodysplastic syndromes (MDSs) are generally thought to be diseases of
      elderly patients, younger patients also have rarely been diagnosed with MDS. This
      is a report of the clinical, morphologic and cytogenetic features of 52 cases of
      primary MDS occurring in adults under the age of 50 years. Cases secondary to
      chemotherapy or radiotherapy were excluded. There were 31 males and 21 females.
      The median age at presentation was 39 years (range, 18 to 49 years). The interval
      between onset of symptoms and diagnosis was brief (median, 4 weeks; range, 1-32
      weeks). Of the 49 patients for whom information about duration of symptoms was
      available, 13 (27%) were asymptomatic. Forty-two (81%) of the patients were
      classified using FAB criteria for blood and bone marrow morphology: refractory
      anemia (RA), 11; refractory anemia with ringed sideroblasts (RARS), four;
      refractory anemia with excess blasts (RAEB), 12; chronic myelomonocytic leukemia
      (CMML), three; refractory anemia with excess blasts in transformation (RAEB-T),
      12 patients. Ten patients could not be categorized. Abnormalities involving
      chromosome 7 was the most frequent cytogenetic abnormality (31%). Partial
      chromosomal deletion and chromosome gain were also common abnormalities (22% and
      9%, respectively). Translocations accounted for only 9% of the main cytogenetic
      abnormalities encountered in this patient population. For the 49 patients for
      whom information regarding AML transformation was available, 23 (47%) progressed
      to acute myeloid leukemia, with an overall median time to progression of 2 months
      (range 3 weeks to 3 years). In each category except for RARS, approximately half
      of the patients progressed, with a slightly less median time to progression in
      RAEB-T than for the other subtypes of MDS. Thirteen patients underwent bone
      marrow transplantation at the time of presentation of their disease.

PMID- 11960341
TI  - Arsenic trioxide therapy for relapsed or refractory Japanese patients with acute
      promyelocytic leukemia: need for careful electrocardiogram monitoring.
AB  - Recent studies have shown that arsenic trioxide (As(2)O(3)) can induce complete
      remission in patients with acute promyelocytic leukemia (APL). We tested the
      efficacy and safety of As(2)O(3) for the treatment of patients with APL who had
      relapsed from or become refractory to all-trans retinoic acid (ATRA) and
      conventional chemotherapy in a prospective study. As(2)O(3) at a dose of 0.15
      mg/kg was administered until the date of bone marrow remission to a maximum of 60
      days. In patients who achieved complete remission (CR), one additional course of
      As(2)O(3) was administered using the same dose for 25 days. Of 14 patients, 11
      (78%) achieved CR. Six of 10 patients who achieved CR showed disappearance of PML
      RARalpha transcript by RT-PCR assay. The duration of As(2)O(3)-induced CR ranged
      from 4 to 22 months (median, 8 months) at a median follow-up of 17 months.
      Adverse events included 13 electrocardiogram abnormalities (13 QTc prolongation,
      eight ventricular premature contraction, four nonsustained ventricular
      tachycardia and two paroxysmal supraventricular tachycardia), seven nausea and
      vomiting, four pruritus, three peripheral neuropathy, three fluid retention and
      one APL differentiation syndrome. Four patients received antiarrhythmic agents.
      Hyperleukocytosis developed in five patients and in three cytotoxic drugs were
      necessary. Other adverse events were relatively mild. As(2)O(3) treatment is
      effective and relatively safe in relapsed or refectory patients with APL. Cardiac
      toxicities in patients with QTc prolongation should be carefully monitored.

PMID- 11960343
TI  - Significance of the levels of bone marrow lymphoid infiltrate in chronic
      lymphocytic leukemia patients with nodular partial remission.
AB  - Patients with chronic lymphocytic leukemia (CLL) are considered in nodular
      partial remission (nPR) when they are in remission but bone marrow biopsies show
      rare nodules. The significance of the level of residual disease in nPR is not
      known. We studied 91 previously untreated CLL patients who were treated with
      fludarabine alone, fludarabine with prednisone, or fludarabine with
      cyclophosphamide and achieved nPR at the end of six courses. We compared bone
      marrow lymphoid infiltration before therapy and at the end of three and six
      courses of therapy as evaluated by a pathologist in retrospective fashion with
      that of the routine evaluation at the time of performing bone marrow biopsy. We
      then compared these results with those obtained by computer-aided
      histomorphometry in 28 patients in nPR. There was significant correlation (P <
      0.05) between pathologists as well as between pathologists and histomorphometry.
      Upon correlation with clinical characteristics, there was significant correlation
      (P 0.01) between marrow involvement before therapy and white blood cell counts
      (wbc), hemoglobin (hgb), absolute lymphocyte counts, and beta2-microglobulin
      (beta2-m) but none of these parameters correlated with the lymphoid infiltrate at
      the end of three or six courses of therapy. more importantly, lymphoid
      infiltration after three and six courses did not correlate with time to
      progression (ttp) or overall survival (os). however, patients with >70% marrow
      involvement before therapy had a significantly shorter TTP (P = 0.02). All 91
      patients showed similar results. However, we found reverse correlation between
      marrow lymphoid infiltrate at the end of three courses and OS (P = 0.01).

PMID- 11960344
TI  - Immunoglobulin diversification in B cell malignancies: internal splicing of heavy
      chain variable region as a by-product of somatic hypermutation.
AB  - In this study we describe alternative splicing of somatically mutated
      immunoglobulin (Ig) variable heavy chain (V(H)) genes in three distinct primary B
      cell non-Hodgkin's lymphomas (B-NHL). In two V4-34 expressing lymphomas, ie a
      post-germinal center type B cell chronic lymphocytic leukemia (B-CLL) and a
      follicular lymphoma (FL), internally spliced V(H) gene transcripts were found in
      which a sequence stretch of 116 bp between the framework region 1 (FR1) and
      complementarity determining region 2 (CDR2) had been deleted. We provide evidence
      that for this alternative IgV(H) mRNA processing a known cryptic 5' splice donor
      site and a previously unidentified cryptic 3' splice acceptor site were used.
      Site-directed mutagenesis showed that the cryptic 3' splice acceptor site had
      been activated by specific somatic point mutations. The B-CLL further harbored a
      triplication of the rearranged JH3 gene segment including the putative N region
      and part of the JH3-JH4 intron sequence. This triplication probably took place
      via a repeated mechanism of DNA double strand break followed by homologous
      recombination, a mechanism which was recently proposed also involved in the
      somatic hypermutation process and is compatible with the post-germinal center
      derivation of this B-CLL. Finally, in a V4-34 expressing diffuse large B cell
      lymphoma, we observed alternative IgV(H) mRNA processing using the same cryptic
      5' splice donor site and the normal splice acceptor site of the CH1-C(mu) exon.
      The significance of alternative IgV(H) processing in B cell malignancies and as a
      potential mechanism of somatic Ig diversification is discussed.

PMID- 11960345
TI  - Allogeneic hematopoietic stem cell transplantation for 27 children with juvenile
      myelomonocytic leukemia diagnosed based on the criteria of the International JMML
      Working Group.
AB  - Prognostic factors of juvenile myelomonocytic leukemia (JMML) have not been
      clarified because of its very low incidence and inaccuracy in the diagnosis. The
      purpose of this study was to evaluate children with JMML given an allogeneic
      hematopoietic stem cell transplantation (SCT) and the role of different variables
      potentially influencing outcome in a nationwide survey in Japan based on the
      newly proposed criteria by the International JMML Working Group. The study
      patients were 27 children who underwent SCT among 55 JMML patients
      retrospectively collected in the survey. The source of grafts was HLA-identical
      siblings in 12 cases, HLA-matched unrelated individuals in 10 and others in five.
      Total body irradiation was used in 18 cases. Event-free and overall survival (OS)
      at 4 years after SCT were 54.2 +/- 11.2% (s.e.) and 57.9 +/- 11.0% (s.e.),
      respectively. Six patients died of relapse and three of complications. Patients
      with abnormal karyotypes showed a significantly lower OS than those with normal
      karyotypes (P < 0.001). Patients below 1 year of age showed a significantly
      higher OS than those of 1 year of age or more (P = 0.02). Patients with grade 0-1
      acute graft-versus-host disease (GVHD) or chronic GVHD had a more favorable OS
      than those without them, although they were not statistically significant (P >
      0.05). Other variables studied were not associated with OS. A multivariate
      analysis of these factors yielded the abnormal karyotype as the only significant
      risk factor for lower OS (risk ratio: 11.0; 95% CI: 2.7-45.1).

PMID- 11960346
TI  - Migratory behavior of leukemic cells from acute myeloid leukemia patients.
AB  - The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4
      contribute to stem cell homing and may play a role in the trafficking of leukemic
      cells. Therefore, we analyzed migration across Transwell filters of cells derived
      from bone marrow (BM) or peripheral blood (PB) from 26 acute myeloid leukemia
      (AML) patients. The presence of the extracellular matrix protein fibronectin (FN)
      strongly enhanced the spontaneous and SDF-1-induced migration of leukemic PB and
      BM cells. No differences in spontaneous, SDF-1-induced migration or CXCR-4
      expression were observed between the different AML subtypes. Subsequently, it was
      determined whether SDF-1 preferentially promoted migration of subsets of leukemic
      cells. Leukemic cells expressing CD34, CD38 and HLA-DR were preferentially
      migrating, whereas cells expressing CD14 and CD36 showed diminished migration.
      Analysis of paired PB and BM samples indicated that significantly higher SDF-1
      induced migration was observed in AML for CD34(+) BM-derived cells compared to
      CD34(+) PB-derived cells, suggesting a role for SDF-1 in the anchoring of
      leukemic cells in the BM or other organs. The lower percentage of circulating
      leukemic blasts in patients with a relatively high level of SDF-1-induced
      migration also supports this hypothesis. In conclusion, we have shown that
      primary AML cells are migrating towards SDF-1 independent of the AML subtypes.

PMID- 11960347
TI  - AML1 gene over-expression in childhood acute lymphoblastic leukemia.
AB  - The present study was conducted on a series of 41 Egyptian children with newly
      diagnosed acute lymphoblastic leukemia (ALL) to investigate TEL and AML1
      abnormalities. The TEL-AML1 fusion was observed in six patients both by RT-PCR
      and FISH analyses, with a frequency of 22.2% among the B-lineage group, whereas
      TEL deletion was seen by FISH analysis in seven patients (17.1%). By FISH
      analysis, nine patients (22%) showed evidence of extra AML1 copies. In five of
      these patients the extra copies were due to non-constitutional trisomy 21,
      whereas in the remaining four cases they were due to tandem AML1 copies on
      der(21), as evidenced by metaphase FISH. Unexpectedly however, enhanced AML1
      expression levels were seen by real-time quantitative RT-PCR in 18 out of the 41
      ALL patients (43.9%). This high level of AML1 expression could be an important
      factor contributing to the pathogenesis and progression of childhood ALL. One key
      mechanism for over-expression seems to be the extra copies of AML1, but other
      mechanisms may involve an alteration of the activity of the AML1 promoter. Here,
      we also report two novel findings. The first is an intragenic deletion of TEL
      exon 7 in a case of T cell ALL. This deletion creates a frame-shift and results
      in a truncated protein lacking the C-terminus that includes the ETS domain. This
      shorter TEL is presumably unable to bind DNA. The second finding is a
      rearrangement of AML1 in a case of T cell ALL due to t(4;21)(q31;q22). This is
      the first reported chromosomal translocation where AML1is rearranged in childhood
      T cell ALL.

PMID- 11960348
TI  - ETV6/AML1 fusion by FISH in adult acute lymphoblastic leukemia.
AB  - Dual-color interphase fluorescence in situ hybridization (FISH) with ETV6 and
      AML1 probes was used for the first time on a series of 159 adult patients with
      acute lymphoblastic leukemia (ALL), for detection of the t(12;21)(p13;q22)
      translocation. Seven patients (4.4%) were found, with 50-100% of positive cells,
      of whom one of two tested, proved negative for the fusion product by RT-PCR. Two
      of them, aged 43 and 50 years, are the oldest patients so far confirmed to have
      the translocation. Three who relapsed at 10, 11 and 24 months, suggest that
      adults may not enjoy the good short-term prognosis reported for t(12;21)-positive
      children. Thirty-one-negative cases had signal numbers differing from the two
      expected for each gene. In 15 cases these results were consistent with the
      karyotype. In nine cases with uninformative cytogenetics, the numbers were
      consistent with those for centromeres and indicated a hidden aneuploidy. Loss of
      ETV6 genes in two cases and AML1 amplification in three others were not suspected
      from the cytogenetics. In conclusion, FISH proved to be reliable in defining
      ETV6/AML1 positivity in this group of patients as well as providing valuable
      insights into negative cases.

PMID- 11960350
TI  - Importance of MEK-1/-2 signaling in monocytic and granulocytic differentiation of
      myeloid cell lines.
AB  - Activation of the MEK/ERK/MAP kinase signaling pathway promotes the proliferation
      and survival of hematopoietic cells. The kinases MEK-1, MEK-2, ERK-1/MAPK and ERK
      2/MAPK are activated by phosphorylation at specific sites, and these events can
      be monitored using phospho-specific antibodies. In this report we examined the
      importance of the MEK/ERK/MAP kinase pathway in the monocytic and granulocytic
      differentiation of myeloid cell lines. Induction of monocytic differentiation in
      HL-60 cells by treatment with phorbol 12-myristate 13-acetate (PMA) led to rapid
      and sustained activation of MEK-1/-2, ERK-1/MAPK and ERK-2/MAPK, while induction
      of granulocytic differentiation by retinoic acid (RA) caused similar activation
      of MEK-1/-2 and ERK-2/MAPK, but not ERK-1/MAPK. The total levels of these kinases
      were not affected during the course of differentiation along either pathway.
      Pretreatment of cells with 5 microM of the MEK-1/-2-specific inhibitor U0126
      abrogated PMA- or RA-induced activation of ERK-1/MAPK and ERK-2/MAPK.
      Importantly, pretreatment of HL-60 cells with U0126 was found to potently inhibit
      both monocytic and granulocytic differentiation, as assessed by cytochemical
      staining for non-specific esterase or nitroblue tetrazolium reduction, flow
      cytometric analysis of myeloid surface markers, and immunoblotting for the cell
      cycle inhibitor p21 WAF1/Cip1. Similar results were seen in U937 cells, where
      U0126 inhibited PMA-induced monocytic differentiation, and in 32D cells, where G
      CSF-induced granulocytic differentiation was inhibited by U0126 pretreatment.
      Additional experiments revealed that inhibition of MEK-1/-2 in HL-60 cells
      resulted in nearly complete inhibition of differentiation-induced cell death
      during monocytic differentiation. By contrast, U0126 only partially inhibited
      cell death resulting from granulocytic differentiation. Taken together, our
      findings demonstrate that the MEK/ERK/MAP kinase signaling pathway is activated,
      and plays a critical role, during both monocytic and granulocytic differentiation
      of myeloid cell lines.

PMID- 11960349
TI  - Downregulation of IL-6-induced STAT3 tyrosine phosphorylation by TGF-beta1 is
      mediated by caspase-dependent and -independent processes.
AB  - To explore the possible cross-talk between the IL-6 and TGF-beta1 pathways in AML
      blast cells, the effect of TGF-beta1 pretreatment on IL-6-induced STAT3 tyrosine
      phosphorylation was studied. A reduction of STAT3 tyrosine phosphorylation after
      TGF-beta1 pretreatment was observed in four out of 40 AML cases (10%), although
      all of the AML cases responded to TGF-beta1 by means of SMAD3 translocation. The
      reduced IL-6-mediated STAT3 tyrosine phosphorylation after pre-treatment with TGF
      beta1 was associated with apoptosis and coincided with the degradation of certain
      cellular proteins, including JAK1 and -2 and Tyk2, without affecting the ERK
      expression and phosphorylation. Furthermore, treatment of AML blasts with the
      cytostatic agent VP16, as an alternative way to induce apoptosis, resulted in a
      similar degree of degradation of JAK kinases and concomitant reduction of IL-6
      mediated STAT3 tyrosine phosphorylation. Although degradation of JAK kinases
      could be rescued by incubating the cells with the pan-caspase inhibitor Z-VAD
      fmk, the attenuating effect of TGF-beta1 treatment on the STAT3 tyrosine
      phosphorylation was still partly present. It was shown that in AML cells cultured
      in the presence of Z-VAD-fmk, TGF-beta1 pretreatment resulted in a reduction of
      JAK1 phosphorylation upon IL-6 stimulation. Expression of SOCS1 and -3 could be
      ruled out as a possible cause of reduced JAK1 phosphorylation levels in the
      investigated AML case.

PMID- 11960351
TI  - Analysis of CD20-dependent cellular cytotoxicity by G-CSF-stimulated neutrophils.
AB  - Rituximab, a chimeric CD20 monoclonal antibody (mAb), is widely used in the
      treatment of patients with low-grade non-Hodgkin's lymphoma. Possible anti-tumour
      mechanisms involve complement-mediated lysis and/or antibody-dependent cellular
      cytotoxicity (ADCC). Because G-CSF greatly enhances the cytotoxicity of
      neutrophils (PMN) in ADCC, the clinical efficacy of rituximab might be enhanced
      by the addition of G-CSF. Therefore, we investigated the neutrophil-mediated CD20
      dependent cellular cytotoxicity in B cell lines. In contrast to previous studies
      by others, we found that G-CSF-primed PMN are capable of functioning as effector
      cells in CD20-dependent cellular cytotoxicity. However, HLA class II mAbs were
      far more effective. The differences between HLA class II- and CD20-mediated PMN
      ADCC were not due to: (1) the use of chimeric (hIgG1) mAbs vs mIgG2a mAbs; (2)
      HLA class II-induced apoptosis as an 'ADCC-sensitising' mechanism; (3) CD20
      induced inhibition of ADCC; (4) inferior membrane mobility of CD20. Analysis of
      Fcgammareceptor (FcgammaR) involvement showed that although CD20-induced ADCC was
      mediated mainly via FcgammaRI, for optimal lysis FcgammaRI and FcgammaRII were
      both required. In contrast, in HLA class II-dependent ADCC both FcgammaRI and II
      were capable of independently inducing maximum lysis. The mechanism underlying
      these differences in FcgammaR-binding and activation remains to be elucidated.

PMID- 11960352
TI  - T and B leukemic cell lines exhibit different requirements for cell death:
      correlation between caspase activation, DFF40/DFF45 expression, DNA fragmentation
      and apoptosis in T cell lines but not in Burkitt's lymphoma.
AB  - The execution phase of apoptosis occurs through the activation and function of
      caspases which cleave key substrates that orchestrate the death process. Here, we
      have compared the sensitivity of various T and B cell lines to death receptor or
      staurosporine-induced apoptosis. First, we found a lack of correlation between
      death receptor expression and sensitivity to Fas or Trail. By contrast, a
      correlation between caspase activation, DNA fragmentation and cell death in T
      cell lines was evidenced. Among T cells, CEM underwent apoptosis in response to
      CH11 but were resistant to Trail in agreement with the absence of Trail receptors
      (DR4 and DR5) on their surface. The B cell line SKW 6.4 was sensitive to CH11 and
      staurosporine but resistant to Trail. As B cell lines expressed significant
      levels of DR4 and DR5, resistance to Trail in SKW 6.4 is likely due to the
      expression of the decoy receptor DcR1. Burkitt's lymphoma such as RPMI 8866 and
      Raji did not exhibit DNA fragmentation in response to CH11, Trail or
      staurosporine but showed long-term caspase-dependent loss of viability upon
      effector treatment. The B cell lines used in this study express very weak or
      undetectable levels of DFF40 and relatively high levels of DFF45. Interestingly,
      cytosolic extracts from RPMI 88.66 but not other B lymphoma exhibit altered
      levels of cytochrome c-dependent caspase activation. Taken together, our results
      show that: (1) death receptor expression does not correlate with sensitivity to
      apoptosis; (2) the very low ratio of DFF40 vs. DFF45 is unlikely to explain by
      itself the lack of DNA fragmentation observed in certain B cell lines; and (3) a
      defective cytochrome c-dependent caspase activation might account at least in
      part for the insensitivity of certain Burkitt's lymphoma (RPMI 88.66) to
      apoptosis. Thus it seems that resistance of Burkitt's lymphoma to apoptosis is
      not governed by a general mechanism, but is rather multifactorial and differs
      from one cell line to another.

PMID- 11960353
TI  - Nitric oxide induces the apoptosis of human BCR-ABL-positive myeloid leukemia
      cells: evidence for the chelation of intracellular iron.
AB  - Anti-leukemia activity of human macrophages involves the generation of nitric
      oxide (NO) derivatives. However, leukemic transformation may involve mechanisms
      that rescue cells from NO-mediated apoptosis. In the present work, we analyzed
      the effects of exogenous NO on the proliferation of BCR-ABL(+) chronic
      myelogenous leukemia (CML) cells. As normal leukocytes, the proliferation of
      leukemia cells was inhibited by SNAP (S-nitroso-N-acetyl-penicillamine), GEA
      (Oxatriazolium amino-chloride), and SIN-1 (Morpholino-sydnonimine), whereas SNP
      (sodium nitroprusside) had no effect on leukemia cell growth. SIN-1 induced
      higher anti-proliferation activity in BCR-ABL(+) cells, compared to normal
      hemopoietic cells. Inhibition of leukemia cell proliferation correlated with
      increased apoptosis and DEVDase activity. The simultaneous addition of exogenous
      iron reversed NO-mediated inhibition of cell growth, caspase activation and
      apoptosis in all BCR-ABL(+) cells tested. The quantification of intracellular
      iron levels in leukemia cells indicated that NO induced an early, dose-dependent
      decrease in ferric iron levels. Accordingly, elevation of intracellular iron
      protected leukemia cells from NO-mediated apoptosis. Together, the present work
      reveals the presence of an iron-dependant mechanism for leukemia cell rescue from
      NO-induced growth inhibition and apoptosis.

PMID- 11960354
TI  - Antibody status to HHV-6 in children with leukaemia.
AB  - Forty children with acute lymphoblastic (33) or myeloid leukaemia (seven) were
      studied for IgG and IgM antibodies and IgG avidity against human herpesvirus 6
      (HHV-6) at the time of diagnosis, and compared with age-, sex- and season-matched
      children with various neurological diseases of suspected viral origin. Of the
      children with leukaemia, 97.5% had IgG antibodies and 40% IgM antibodies to HHV-6
      compared with 92.3% and 7.7% of reference subjects (P = 0.005). A seronegative
      child with leukaemia seroconverted 3 weeks after the diagnosis. The avidity of
      IgG antibodies (based on the resistance to urea treatment) was high in all
      children with leukaemia. One reference child had HHV-6-specific IgG antibodies
      with low avidity, which together with his positive IgM indicated an acute
      infection. The presence of specific IgM antibodies in 40% of children with
      leukaemia and the high avidity of IgG suggest a reactivation or an inaproppriate
      primary response to HHV-6 infection. The results support the conclusion of the
      role of the HHV-6 infection at the onset of childhood leukaemia.

PMID- 11960355
TI  - Acute lymphoblastic leukemia incidence during socioeconomic transition: selective
      increase in children from 1 to 4 years.
AB  - Pre-school acute lymphoblastic leukemia (ALL) peak is consistent in developed but
      not in developing countries and its magnitude apparently correlates with the
      socioeconomic status. A population-based study describing ALL incidence during
      socioeconomic transition has been lacking. Central European post-communist
      countries (with very low foreign migration and centralized statistics) offer
      reliable data for the period before and during major socioeconomic changes.
      Population-based data on Czech ALL patients younger than 18 years were taken from
      two independent Czech national registries partially overlapping in time (1980
      1998, n = 1236 and 1991-1999, n = 570). During the 1980s and 1990s, ALL incidence
      among children 1-4 years increased 1.5 times (P = 0.01). This increase was more
      prominent in females than in males (slopes 0.13 and 0.09, P values 0.03 and
      >0.05, respectively). No significant change was observed in other age groups (0,
      5-9, 10-14, 15-17 years or all others combined). We discuss possible underlying
      socioeconomic factors including infant care and breast-feeding, hygiene, birth
      order, industry and pollution. Moreover, we try to pinpoint the
      immunophenotypic/molecular-genetic subsets of ALL that might be socioeconomically
      affected. Selective increase of ALL in children 1-4 years old provides
      epidemiological evidence that etiology and/or trigger mechanisms are different
      for a considerable proportion of these children and that these mechanisms are
      exogenous.

PMID- 11960356
TI  - Relationship between expression of genes involved in cell cycle control and
      apoptosis in diffuse large B cell lymphoma: a preferential survivin-cyclin B
      link.
AB  - Accumulating evidence suggests that lack of balance between proliferation and
      apoptosis may lead to clonal expansion and cancer emergence. In diffuse large B
      cell lymphoma (DLBCL), survivin expression by tumor cells has been recently
      described as a poor prognostic marker. We assessed the relationship between
      survivin gene up-regulation and several other factors involved in either cell
      cycle or apoptosis control. The expression of 34 genes from 27 cases of DLBCL
      with typical IPI factor-related poor prognostic outcome was analyzed by RNase
      protection assay. Using non-neoplastic tissues and low grade lymphomas as
      control, survivin expression was high in 80% of the cases without significant
      relation to patient overall survival (P = 0.64). However, the expression of
      several genes encoding for cell cycle inhibitors, cyclins, Bcl-2 or IAP family
      factors was significantly associated with the survivin up-regulation. Gene
      expression profiling showed that both survivin and cyclin B expression can define
      two subgroups of DLBCL: the previously described germinal center-like and
      activated B-like lymphomas, determined by protein expression analysis. We also
      identified a preferential survivin-cyclin B relationship (P = 0.017), suggesting
      that cyclin B over-expression, when linked to survivin over-expression in
      aggressive forms of lymphoma, might demonstrate a specific G2/M transition
      promotion.

PMID- 11960357
TI  - Immunologic manipulation in AML: from bench to bedside.

PMID- 11960358
TI  - Mpl and the hematopoietic stem cell.

PMID- 11960359
TI  - Cooperativity between mutations in tyrosine kinases and in hematopoietic
      transcription factors in AML.

PMID- 11960360
TI  - Postremission therapy in older adults with acute myeloid leukemia: an opportunity
      for new drug development.

PMID- 11960361
TI  - Therapy of secondary leukemia.

PMID- 11960362
TI  - Long-term outcome of allogeneic transplants in acute myeloid leukemia.

PMID- 11960363
TI  - Mixed allogeneic chimerism and graft-versus-leukemia effects in acute myeloid
      leukemia.

PMID- 11960364
TI  - A single split-signal FISH probe set allows detection of TAL1 translocations as
      well as SIL-TAL1 fusion genes in a single test.
AB  - About 30% of T cell acute lymphoblastic leukemias (T-ALL) carry TAL1 gene
      aberrations. In the majority of cases (approximately 25%), this concerns a
      submicroscopic deletion of approximately 90 kb in chromosome region 1p32, which
      deletes the coding regions of the SIL gene and the untranslated region of the
      TAL1 gene, thereby placing the TAL1 gene under control of the SIL promoter
      region. Translocation (1;14)(p32;q11) involving the TAL1 gene occurs at a much
      lower frequency (3%), whereas some other rare variant translocations have been
      described as well. In this study we developed a set of TAL1 FISH probes based on
      the split-signal FISH principle that enables detection of both types of TAL1 gene
      aberrations in single test. For this purpose, one probe was designed downstream
      of the TAL1 gene (TAL1-D) and the second probe in the region upstream of the TAL1
      gene, partly covering the SIL gene (SIL-U). We show that this split-signal FISH
      probe set allows reliable detection of the unaffected SIL-TAL1 gene region with a
      fusion signal, SIL-TAL1 fusion genes with loss of the SIL-U signal, and TAL1 gene
      translocations with a split-signal, independent of the involved partner gene.

PMID- 11960365
TI  - A competitive PCR-based method using TCRD, TCRG and IGH rearrangements for rapid
      detection of patients with high levels of minimal residual disease in acute
      lymphoblastic leukemia.

PMID- 11960366
TI  - Polymorphisms in methylenetetrahydrofolate reductase and methotrexate sensitivity
      in childhood acute lymphoblastic leukemia.

PMID- 11960367
TI  - Induction of human MDR1 gene expression by 2-acetylaminofluorene is mediated by
      effectors of the phosphoinositide 3-kinase pathway that activate NF-kappaB
      signaling.
AB  - The expression of P-glycoprotein encoded by the multidrug resistance (MDR1) gene
      is associated with the emergence of the MDR phenotype in cancer cells. Human MDR1
      and its rodent homolog mdr1a and mdr1b are frequently overexpressed in liver
      cancers. However, the underlying mechanisms are largely unknown. The
      hepatocarcinogen 2-acetylaminofluorene (2-AAF) efficiently activates rat mdr1b
      expression in cultured cells and in Fisher 344 rats. We recently reported that
      activation of rat mdr1b in cultured cells by 2-AAF involves a cis-activating
      element containing a NF-kappaB binding site located -167 to -158 of the rat mdr1b
      promoter. 2-AAF activates IkappaB kinase (IKK), resulting in degradation of
      IkappaBbeta and activation of NF-kappaB. In this study, we report that 2-AAF
      could also activate the human MDR1 gene in human hepatoma and embryonic
      fibroblast 293 cells. Induction of MDR1 by AAF was mediated by DNA sequence
      located at -6092 which contains a NF-kappaB binding site. Treating hepatoma cells
      with 2-AAF activated phosphoinositide 3-kinase (PI3K) and its downstream
      effectors Rac1, and NAD(P)H oxidase. Transient transfection assays demonstrated
      that constitutively activated PI3K and Rac1 enhanced the activation of the MDR1
      promoter by 2-AAF. Treatment of hepatoma cells with 2-AAF also activated another
      PI3K downstream effector Akt. Transfection of recombinant encoding a dominant
      activated Akt also enhanced the activation of MDR1 promoter activation by 2-AAF.
      These results demonstrated that 2-AAF up-regulates MDR1 expression is mediated by
      the multiple effectors of the PI3K signaling pathway.

PMID- 11960368
TI  - Phosphorylation of HDM2 by Akt.
AB  - The HDM2 protein is a key regulator of the tumour suppressor, p53. Control of
      HDM2 function is critical for normal cell proliferation and stress responses, and
      it is becoming evident that multiple modifications of HDM2 can regulate its
      function within cells. In this study we show that HDM2 associated with the serine
      threonine kinase, Akt, in response to growth factor stimulation of human primary
      cells. This association was concurrent with phosphorylation of Akt (at Ser 473),
      and resulted in elevated expression of HDM2 and enhanced nuclear localization.
      However, analysis of HDM2 proteins mutated at the consensus Akt recognition sites
      at serines 166 and 186 indicated that modification at these residues was not
      sufficient for the increased expression of the protein, which was blocked by the
      PI3 kinase inhibitor LY294002. Tryptic peptide and mutational analyses revealed
      evidence for an Akt phosphorylation site in HDM2 additional to the two consensus
      sites.

PMID- 11960369
TI  - Cell permeable BH3-peptides overcome the cytoprotective effect of Bcl-2 and Bcl
      X(L).
AB  - Peptides corresponding to the BH3 domains of Bax (BaxBH3) or Bcl-2 (Bcl2BH3) are
      potent inducers of apoptosis when fused to the Atennapedia plasma membrane
      translocation domain (Ant). BaxBH3Ant and Bcl2BH3Ant caused a mitochondrial
      membrane permeabilization (MMP) and apoptosis, via a mechanism that was not
      inhibited by overexpressed Bcl-2 or Bcl-X(L), yet partially inhibited by
      cyclosporin A (CsA), an inhibitor of the mitochondrial permeability transition
      pore. When added to isolated mitochondria, BaxBH3 and Bcl2BH3 induced MMP, which
      was inhibited by CsA. However, Bcl-2 or Bcl-X(L) failed to inhibit MMP induced by
      BaxBH3 and Bc2BH3 in vitro, while they efficiently suppressed the induction of
      MMP by the Vpr protein (from human immunodeficiency virus-1), a ligand of the
      adenine nucleotide translocator (ANT). BaxBH3 but not Bcl2BH3 was found to
      interact with ANT, and only BaxBH3 (not Bcl2BH3) permeabilized ANT
      proteoliposomes and induced ANT to form non-specific channels in
      electrophysiological experiments. In contrast, both BaxBH3 and Bcl2BH3 were able
      to stimulate channel formation by recombinant Bax protein. Thus, BaxBH3 might
      induce MMP via an action on at least two targets, ANT and Bax-like proteins. In
      contrast, Bcl2BH3 would elicit MMP in an ANT-independent fashion. In purified
      mitochondria, two ligands of ANT, bongkrekic acid and the protein vMIA from
      cytomegalovirus, failed to prevent MMP induced by BaxBH3 or Bcl2BH3. In
      conclusion, BaxBH3 and Bcl2BH3 induce MMP and apoptosis through a mechanism which
      overcomes cytoprotection by Bcl-2 and Bcl-X(L).

PMID- 11960370
TI  - Phorbol esters inhibit fibroblast growth factor-2-stimulated fibroblast
      proliferation by a p38 MAP kinase dependent pathway.
AB  - Treatment of fibroblasts with the phorbol ester, 12-O-tetradecanoyl phorbol 13
      acetate (TPA), specifically inhibits fibroblast growth factor-2 (FGF-2) induced
      proliferation. TPA treatment has little or no effect on FGF receptor activation
      but specifically inhibits the activation of p38 MAPK but not other downstream
      signaling pathways implicated in cell proliferation. p38 MAPK was recently shown
      to be required for the FGF-2-stimulated proliferation of fibroblasts. The effect
      of TPA on both p38 MAPK activation and cell proliferation can be reversed by
      treatment with the PKC inhibitor Go6983. The TPA-mediated inhibition of p38 MAPK
      activation requires phosphatase activity and is at least partially mediated by
      ERKs since it is reduced by treatment with the MEK inhibitor PD98059. In
      contrast, the FGF-2-stimulated differentiation of PC12 cells, which express the
      same FGF receptor as Swiss 3T3 fibroblasts, is not affected by TPA treatment,
      consistent with a lack of involvement of p38 MAPK activity in this process. These
      data indicate that the effects of TPA treatment on cellular function are not only
      cell type but also stimulus specific and are dependent upon the distinct pathways
      activated downstream of each stimulus.

PMID- 11960371
TI  - Gap junction intercellular communication propagates cell death in cancerous
      cells.
AB  - Gap junction intercellular communication (GJIC) or cell coupling has an important
      function in maintaining tissue homeostasis and is thus a critical factor in the
      life and death balance of cells. While the role of GJIC in cell growth regulation
      has been much studied, its involvement in apoptosis remains unclear. In this
      study we elucidated the possibility that cell death is propagated via gap
      junctions, employing the rat bladder carcinoma cell line BC31. BC31 cells
      proliferate quickly, are tumorigenic, and are well-coupled via gap junctions that
      contain the gap junction protein Connexin43 (Cx43). In addition, these cells are
      predisposed to spontaneous death by apoptosis, particularly upon achieving
      confluency. We found that many dying BC31 cells express Cx43 just as their non
      apoptotic counterparts do. Furthermore, Cx43 in apoptotic cells could be
      functionally competent, supporting coupling of these cells with their non
      apoptotic neighbors, and as a result, clusters of coordinately dying cells were
      observed. The role of Cx43 and GJIC in propagating cell death was shown by
      analysing clones of BC31 cells expressing a mutant of Cx43 that is a dominant
      negative inhibitor of GJIC, and by using beta-glycyrrhetinic acid to inhibit
      intrinsic cell coupling in BC31 cells: in both cases the formation of clusters of
      dying cells was abrogated, and the intensity of cell death was considerably
      decreased. These results suggest that GJIC spreads cell-killing signals initially
      generated by a single cell that spontaneously initiates apoptosis, into healthy
      surrounding cells, thus increasing the level of cell death. Treatment of BC31
      cells with the sleep-inducing lipid Oleamide, which selectively restricts gap
      junction permeability to Ca(2+) ions, did not abrogate coordinated cell death by
      clusters, indicating that Ca(2+) ions are the most probable cell-killing signals
      spread through gap junctions.

PMID- 11960372
TI  - Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis.
AB  - Non-receptor and receptor tyrosine kinases, such as Src and EGF receptor (EGFR),
      are major inducers of vascular endothelial growth factor (VEGF), one of the most
      potent mediators of angiogenesis. While tyrosine kinases signal through multiple
      pathways, signal transducer and activation of transcription 3 (Stat3) is a point
      of convergence for many of these and is constitutively activated with high
      frequency in a wide range of cancer cells. Here, we show that VEGF expression
      correlates with Stat3 activity in diverse human cancer cell lines. An activated
      Stat3 mutant (Stat3C) up-regulates VEGF expression and stimulates tumor
      angiogenesis. Stat3C-induced VEGF up-regulation is abrogated when a Stat3-binding
      site in the VEGF promoter is mutated. Furthermore, interrupting Stat3 signaling
      with dominant-negative Stat3 protein or Stat3 antisense oligonucleotide in tumor
      cells down-regulates VEGF expression. Consistent with an important role of Stat3
      in VEGF up-regulation induced by various oncogenic tyrosine kinases, v-Src
      mediated VEGF expression is inhibited when Stat3 signaling is blocked. Moreover,
      chromatin immunoprecipitation assays indicate that Stat3 protein binds to the
      VEGF promoter in vivo and mutation of a Stat3-binding site in the VEGF promoter
      abrogates v-Src-induced VEGF promoter activity. These studies provide evidence
      that the VEGF gene is regulated directly by Stat3 protein, and indicate that
      Stat3 represents a common molecular target for blocking angiogenesis induced by
      multiple signaling pathways in human cancers.

PMID- 11960373
TI  - Induction of the interleukin-2/15 receptor beta-chain by the EWS-WT1
      translocation product.
AB  - EWS-WT1 is a chimeric transcription factor resulting from fusion of the N
      terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc
      fingers of the Wilms tumor suppressor WT1. This translocation underlies
      desmoplastic small round cell tumor (DSRCT), which is noted for the abundance of
      reactive stroma surrounding islets of tumor cells, suggestive of paracrine
      signals contributing to tumor cell proliferation. Hybridization to high-density
      oligonucleotide microarrays can be used to identify targets of EWS-WT1.
      Expression of EWS-WT1 from a tetracycline-regulated promoter leads to the
      induction of growth-associated genes, of which the most remarkable is the beta
      chain of the interleukin-2/15 receptor (IL-2/15Rbeta). Potent transcriptional
      activation by the chimeric protein maps to two bindings sites within the IL
      2/15Rbeta promoter. Analysis of primary DSRCT tumor specimens demonstrates high
      levels of IL-2/15Rbeta within the tumor cells, along with expression of IL-2 and
      IL-15 by the abundant hyperplastic endothelial cells within the reactive stroma.
      Activation of this cytokine signaling pathway is consistent with the nuclear
      localization of its downstream effectors, phosphorylated STAT3 and STAT5. These
      observations suggest that the transcriptional induction of a cytokine receptor by
      a tumor-associated translocation product enables a proliferative response of
      epithelial cancer cells to ligands secreted by the surrounding stroma.

PMID- 11960374
TI  - P53 mediates ceramide-induced apoptosis in SKN-SH cells.
AB  - Ceramide induces apoptotic cell death in a dose- and time-dependent manner in
      neuroblastoma SKN-SH cells. Pretreatment with caspase inhibitors blocks cell
      death, suggesting that a set of caspase activities including caspase 1, as well
      as caspase 3, are involved in ceramide-induced apoptosis in SKN-SH cells.
      Treatment with a caspase inhibitor 3 h after ceramide addition did not inhibit
      cell death, although caspase activity was substantially reduced. Ceramide-induced
      apoptosis is accompanied by accumulation of p53 followed by an increase of Bax
      and decrease of Bcl-2 levels. Inhibition of p53 expression with p53 antisense
      oligonucleotides inhibits apoptosis and prevents the increase in Bax and decrease
      in Bcl-2. Furthermore, pretreatment with p53 antisense oligonucleotides markedly
      inhibits the induction of caspase activity. These results suggest that p53
      regulates the ratio Bcl-2/Bax and the expression/activation of caspases during
      ceramide-induced apoptosis in SKN-SH cells. Caspase inhibition did not alter the
      expression of p53, Bcl-2 and Bax. Thus ceramide-induced reduction in the Bcl
      2/Bax ratio, increase in caspase activity, and apoptosis is dependent upon
      increases in cellular p53 levels which play a critical role in the regulation of
      apoptotic cell death.

PMID- 11960375
TI  - The mesenchyme expresses T cell receptor mRNAs: relevance to cell growth control.
AB  - The mesenchyme plays a crucial regulatory role in organ formation and
      maintenance. However, comprehensive molecular characterization of these cells is
      lacking. We found unexpectedly that primary mesenchyme, as well as mesenchymal
      cell clones, express T cell receptor (TCR)alphabeta mRNAs, lacking the variable
      region. Immunological and genetic evidence support the expression of a
      corresponding TCRbeta protein. Additionally, mRNAs encoding TCR complex
      components including CD3 and zeta chain are present. A relatively higher
      expression of the mesenchymal TCRbeta mRNA by cultured mesenchymal cell clones
      correlates with fast growth, whereas poorly expressing cells are slow growers and
      are contact inhibited. The clones that express relatively higher amount of the
      TCR mRNA exhibit an increased capacity to form tumors in nude mice. However, the
      expression of this mRNA in the mesenchyme is not per se leading to tumorigenesis,
      as demonstrated by primary mesenchyme that does not form tumors in mice while
      expressing moderate amounts of the TCR transcripts. The expression of mesencymal
      TCRbeta was confined to the G2/M phases of the cell cycle in the MBA-13
      mesenchymal cell line. This cell cycle dependent expression, considered together
      with the correlation between growth properties and the level of TCR expression by
      cell clones, implies association of mesenchymal TCR with cell growth control.

PMID- 11960377
TI  - Overexpression of B-type cyclins alters chromosomal segregation.
AB  - To identify genes which overexpression results into chromosomal instability
      (CIN), we developed a biological approach based on a yeast indicator strain in
      which CIN can be detected by a sectoring phenotype. Screening in this strain of a
      yeast genomic library cloned into a high copy vector led us to identify, among
      the clones generating 100% of sectoring colonies, Clb5, one of the six B-type
      cyclins present in yeast. Overexpression of cyclin B2 and cyclin B1, the two
      human homologs of Clb5, in the CIN indicator strain resulted also into a
      sectoring phenotype and induced, like overexpression of Clb5, an abnormal
      sensitivity to benomyl, indicating that overexpression of B-type cyclins alters
      the spindle checkpoint. In a series of 38 primary colorectal cancers, we detected
      in five tumors (13%) an accumulation of cyclin B1, which was neither related to
      mRNA overexpression nor to mutation within the coding region, and in five other
      tumors (13%) a 2-10-fold increase of cyclin B2 mRNA which was not related to gene
      amplification. These results suggest that overexpression of cyclins B, resulting
      from different mechanisms, could contribute, through an alteration of the spindle
      checkpoint, to the chromosomal instability observed in cancer.

PMID- 11960376
TI  - UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction
      blocking drug.
AB  - Protein-protein interactions play critical regulatory roles in mediating signal
      transduction. Previous studies have identified an unconventional, small-molecule,
      Src signal transduction inhibitor, UCS15A. UCS15A differed from conventional Src
      inhibitors in that it did not alter the levels or the tyrosine kinase activity of
      Src. Our studies suggested that UCS15A exerted its Src-inhibitory effects by a
      novel mechanism that involved the disruption of protein-protein interactions
      mediated by Src. In the present study we have examined the ability of UCS15A to
      disrupt the interaction of Src-SH3 with Sam68, both in vivo and in vitro. This
      ability of UCS15A was not restricted to Src-SH3 mediated protein-protein
      interactions, since the drug was capable of disrupting the in vivo interactions
      of Sam68 with other SH3 domain containing proteins such as Grb2 and PLCgamma. In
      addition, UCS15A was capable of disrupting other typical SH3-mediated protein
      protein interactions such as Grb2-Sos1, cortactin-ZO1, as well as atypical SH3
      mediated protein-protein interactions such as Grb2-Gab1. However, UCS15A was
      unable to disrupt the non-SH3-mediated protein-protein interactions of beta
      catenin, with E-cadherin and alpha-catenin. In addition, UCS15A had no effect on
      the SH2-mediated interaction between Grb2 and activated Epidermal Growth Factor
      receptor. Thus, the ability of UCS15A, to disrupt protein-protein interactions
      appeared to be restricted to SH3-mediated protein-protein interactions. In this
      regard, UCS15A represents the first example of a non-peptide, small molecule
      agent capable of disrupting SH3-mediated protein-protein interactions. In vitro
      analyses suggested that UCS15A did not bind to the SH3 domain itself but rather
      may interact directly with the target proline-rich domains.

PMID- 11960378
TI  - Constitutive activation of Stat3alpha in brain tumors: localization to tumor
      endothelial cells and activation by the endothelial tyrosine kinase receptor
      (VEGFR-2).
AB  - Members of the normally latent family of transcription factors signal/inducers
      and activators of transcription (Stat) are activated in a number of human tumors
      and tumor-derived cell lines. In the case of Stat3, it is believed that this
      activation leads to the induction of survival signals as well as increased
      proliferation. In this study, we demonstrate that Stat3 is constitutively
      activated in glioma and medulloblastoma tumors and that the activated protein
      localizes predominantly to the tumor endothelial cells in the highly vascularized
      glioma tumors. Our efforts to elucidate potential mechanism(s) for this activated
      protein have shown that coexpression of Stat3alpha and the vascular endothelial
      growth factor receptor-2 (VEGFR-2) result in ligand-independent activation of
      Stat3alpha tyrosine phosphorylation and subsequent transcriptional activation in
      non-endothelial cells. We also show that activated Stat3alpha can increase
      transcription from the vascular endothelial growth factor (VEGF) gene. Taken
      together, these results suggest that the activated Stat3alpha found in brain
      tumors may be due to the endothelial tyrosine kinase VEGFR-2 and that Stat3alpha
      may play a central role in autocrine VEGF activation.

PMID- 11960379
TI  - Identification of signal transduction pathways involved in constitutive NF-kappaB
      activation in breast cancer cells.
AB  - Nuclear factor-kappaB (NF-kappaB) is usually maintained in an inactive form in
      the cytoplasm through its association with inhibitor of kappaB (IkappaB)
      proteins, and is activated upon stimulation of cells with a variety of signals.
      However, constitutive activation of NF-kappaB is observed in a number of cancers
      including breast cancer. The signaling pathways that are involved in constitutive
      NF-kappaB activation remain largely unknown. Using breast cancer cell lines
      derived from transgenic mice that overexpress specific oncogene/growth factors in
      the mammary gland, we show that heregulin but not her2/neu, c-Myc or v-Ha-ras
      plays a major role in constitutive NF-kappaB activation. Her2/neu potentiated
      tumor necrosis factor alpha (TNFalpha)-inducible NF-kappaB activation whereas c
      Myc potentiated 12-o-tetracecanyolphorbol-13-acetate (TPA)-induced NF-kappaB
      activation. Heregulin-mediated NF-kappaB activation correlated with
      phosphorylation of epidermal growth factor receptor (EGFR) and ErbB3 but not
      her2/neu. Tryphostin AG1517, which inhibits heregulin-mediated phosphorylation of
      EGFR, her2/neu and ErbB3 reduced NF-kappaB activation. In contrast, emodin, which
      blocks phosphorylation of her2/neu by heregulin, failed to reduce NF-kappaB
      activation. These results suggest that heregulin induces NF-kappaB independent of
      her2/neu. PI3 kinase/AKT, protein kinase A (PKA) and IkappaB kinase appear to be
      downstream signaling molecules involved in NF-kappaB activation as specific
      inhibitors of these kinases but not inhibitors of ERK/MAP kinase or protein
      kinase C reduced heregulin-mediated NF-kappaB activation. Based on these results,
      we propose that heregulin increases the expression of pro-invasive, pro
      metastatic and anti-apoptotic genes in cancer cells through autocrine activation
      of NF-kappaB, which leads to invasive and drug-resistant growth of breast cancer.

PMID- 11960380
TI  - Bloom's syndrome protein response to ultraviolet-C radiation and hydroxyurea
      mediated DNA synthesis inhibition.
AB  - Bloom's syndrome (BS) arises through mutations in both copies of the BLM gene
      that encodes a RecQ 3'-5' DNA helicase. BS patients are predisposed to developing
      all the cancers that affect the general population, and BS cells exhibit marked
      genetic instability. We showed recently that BLM protein contributes to the
      cellular response to ionizing radiation by acting as downstream ATM kinase
      effector. We now show that following UVC treatment, BLM-deficient cells exhibit a
      reduction in the number of replicative cells, a partial escape from the G2/M cell
      cycle checkpoint, and have an altered p21 response. Surprisingly, we found that
      hydroxyurea-treated BLM-deficient cells exhibit an intact S phase arrest, proper
      recovery from the S phase arrest, and intact p53 and p21 responses. We also show
      that the level of BLM falls sharply in response to UVC radiation. This UVC
      induced reduction in BLM does not require a functional ATM gene and does not
      result from a subcellular compartment change. Finally, we demonstrate that
      exposure to UVC and hydroxyurea treatment both induce BLM phosphorylation via an
      ATM-independent pathway. These results are discussed in the light of their
      potential physiological significance with regard to the role of BLM in the
      cellular pathways activated by UVC radiation or HU-mediated inhibition of DNA
      synthesis.

PMID- 11960382
TI  - The N-myc and c-myc downstream pathways include the chromosome 17q genes nm23-H1
      and nm23-H2.
AB  - Gain of chromosome 17q material is the most frequent genetic abnormality in
      neuroblastomas. The common region of gain is at least 375 cR large, which has
      precluded the identification of genes with a role in neuroblastoma pathogenesis.
      Neuroblastoma also frequently show amplification of the N-myc oncogene, which
      correlates closely with 17q gain. Both events are strong predictors of
      unfavorable prognosis. To identify genes that are part of the N-myc downstream
      pathway, we constructed SAGE libraries of an N-myc transfected and a control cell
      line. This identified the chromosome 17q genes nm23-H1 and nm23-H2 as being 6-10
      times induced in the N-myc expressing cells. Northern and Western blot analysis
      confirmed this up-regulation. Time-course experiment shows that both genes are
      induced within 4 h after N-myc is switched on. Furthermore, we demonstrate also
      that c-myc can up-regulate nm23-H1 and nm23-H2 expression. Neuroblastoma tumor
      and cell line panels reveal a striking correlation between N-myc amplification
      and mRNA and protein expression of both nm23 genes. We show that the nm23 genes
      are located at the edge of the common region of chromosome 17q gain previously
      described in neuroblastoma cell lines. Our findings suggest that nm23-H1 and nm23
      H2 expression is increased by 17q gain in neuroblastoma and can be further up
      regulated by myc overexpression. These observations suggest a major role for nm23
      H1 and nm23-H2 in tumorigenesis of unfavorable neuroblastomas.

PMID- 11960381
TI  - The new synthetic matrix metalloproteinase inhibitor (Roche 28-2653) reduces
      tumor growth and prolongs survival in a prostate cancer standard rat model.
AB  - The therapeutic efficacy of synthetic inhibitors of matrix-metalloproteinases
      (MMPs) in various cancers has been demonstrated. A novel inhibitor, Ro 28-2653,
      with high selectivity for MMP2, MMP9 and membrane type 1-MMP was evaluated in an
      orthotopic prostate cancer rat model. Efficacy was determined by recording tumor
      growth and survival endpoints. Prostate cancer was induced by inoculating R3327
      Dunning tumor cells (MatLyLu) into the ventral lobe of the prostates of 148
      Copenhagen rats. Daily oral treatment with Ro 28-2653 (10-300 mg/kg per day) was
      started on day 1 or on day 6 after tumor cell injection. Animals were sacrificed
      on day 20 for determination of tumor weights. For survival studies, rats received
      daily oral Ro 28-2653 (100 mg/kg per day) or vehicle for up to 30 days. Tumor
      induction was successful in 100% of the animals. Ro 28-2653 reproducibly reduced
      the tumor weights by up to 90% in a dose-dependent manner. In addition, an
      inhibitory effect in rats with established tumors (treatment start at day 6) was
      shown. A significantly prolonged survival of Ro 28-2653-treated rats was also
      demonstrated. Selective inhibition of MMP activity is a novel therapeutic
      approach, which bears promise for studies in patients with prostate cancer.

PMID- 11960383
TI  - C-terminus of p53 is required for G(2) arrest.
AB  - Mutation of four lysine residues in the p53 C-terminal domain inhibits MDM2
      dependent ubiquitination of p53 and alters its subcellular distribution. This
      implies that modification (such as acetylation and phosphorylation) of amino acid
      residues in p53 C-terminal domain, regulate the biological functions of p53. In
      this study, we demonstrated that p53 with lysine residues 372, 373, 381, and 382
      mutated to alanine (the A4 mutant) retained the transactivation activity of wild
      type p53, although the transactivation activity of p21 promoter by the A4 mutant
      was slightly reduced. The inducible expression of wild-type p53 and the A4 mutant
      in H1299 cells caused growth inhibition due to cell-cycle arrest. Consistent with
      previous studies, the expression of wild-type p53 elicited G(1) and G(2) arrests.
      However, the cells expressing the A4 mutant underwent G(1) arrest but not G(2)
      arrest. Cyclin B1-associated kinase activity was reduced in cells expressing wild
      type p53 but not A4, when the cells underwent G(2) arrest. This suggests that
      modification of the p53 C-terminal domain might inhibit p53-mediated G(2) arrest.
      In other words, p53 requires an intact C-terminus to induce G(2) arrest.

PMID- 11960386
TI  - A new impetus for The Hematology Journal.

PMID- 11960384
TI  - Activation of caspase-3 and cleavage of Rb are associated with p16-mediated
      apoptosis in human non-small cell lung cancer cells.
AB  - The p16 tumor suppressor gene is frequently inactivated in human cancer tissues
      and cell lines. We previously reported that wild-type p16 expression from an
      adenovirus vector (Adv/p16) induced p53-dependent apoptotic cell death in non
      small cell lung cancer (NSCLC) cell lines. Here we show the potential mechanism
      of apoptosis induced by Adv/p16 infection. Infection of human NSCLC cell line
      A549, which carries the wild-type p53 gene, with Adv/p16 resulted in activation
      of caspase-3, accompanied by the cleavage of its substrate poly (ADP-ribose)
      polymerase (PARP), on day 3 of infection. The retinoblastoma (Rb) cell cycle
      regulator protein was also cleaved after activation of caspase-3; when the levels
      of Rb significantly diminished, apoptosis began. When A549 cells were pretreated
      with the caspase-inhibitory peptide N-acetyl-asp-Glu-Val-Asp-CHO (aldehyde) (Ac
      DEVD-CHO), Adv/p16-mediated apoptosis and Rb cleavage were greatly inhibited.
      Furthermore, MDM2, a negative regulator of p53 expression was upregulated 3 days
      after Adv/p16 infection, and MDM2 was subsequently cleaved by caspase-3; MDM2
      cleavage was inhibited by Ac-DEVD-CHO treatment. These data implied that cleavage
      of Rb, in addition to activation of caspase-3, represented a mechanism by which
      Adv/p16 induced apoptotic cell death in human NSCLC cells. Our results support
      the clinical relevance of Adv/p16 as a treatment for p16-null human NSCLC that
      express wild-type p53.

PMID- 11960385
TI  - Aberrant CpG island methylation in cancer cell lines arises in the primary
      cancers from which they were derived.
AB  - A higher prevalence of epigenetic inactivation of tumor suppressor genes has been
      reported in cancer cell line populations compared to primary cancer populations.
      Cancer-related genes are commonly methylated in cancer cell lines but it is not
      known the extent to which tumor suppressor genes may be artificially methylated
      in vitro. We therefore examined 10 pancreatic cancer cell lines and corresponding
      primary tumors for aberrant DNA methylation of promoter CpG islands of eight
      genes and seven CpG islands. Using methylation-specific PCR (MSP), methylation
      was not detected at any of the 15 CpG islands in 15 normal pancreata or in an
      immortalized normal pancreatic duct epithelial (HPDE) cell line. Of 150 loci
      examined, 49 loci were methylated in both primary carcinomas and their
      corresponding cell lines, 95 loci were not methylated in either cell lines or
      their corresponding primary carcinomas. There were four loci methylated only in
      cell lines while another two loci were methylated only in primary carcinomas.
      Overall, the methylation status of primary carcinomas and their cell lines were
      concordant in 96% of cases (144 of 150) (J statistic; J=0.92, P<0.0001). We
      conclude that most of the DNA methylation of tumor suppressor genes observed in
      cancer cell lines is present in the primary carcinomas from which they were
      derived.

PMID- 11960387
TI  - The ABL tyrosine kinase inhibitor STI571 (Glivec) in Philadelphia positive acute
      lymphoblastic leukemia - promises, pitfalls and possibilities.

PMID- 11960388
TI  - Classical and new prognostic factors in chronic lymphocytic leukemia: where to
      now?

PMID- 11960389
TI  - Genetic alterations underlying the pathogenesis of MALT lymphoma.

PMID- 11960390
TI  - Primary orbital lymphoma.

PMID- 11960391
TI  - Repeat abdominal ultrasound evaluation of 100 patients with type I Gaucher
      disease treated with enzyme replacement therapy for up to 7 years.
AB  - With the advent of enzyme replacement therapy for Gaucher disease, there was a
      need to assess response to treatment repeatedly over relatively short periods of
      time; hence abdominal ultrasound was used in our referral clinic because it was
      convenient, safe and inexpensive. In 100 treated patients monitored for 2-7
      years, nearly all had reduction in hepatosplenomegaly. The per cent reduction was
      more dramatic in patients who started treatment when older than 16 years. This
      effect may be explained by a correlation between per cent reduction and degree of
      baseline organomegaly. Because children often initiate therapy sufficiently early
      to preclude developing massive organomegaly, the observed per cent reduction is
      commensurately less. For all patients treated for more than five years, plateau
      ing in response was seen after the first three years of treatment. This study
      permits us to reconsider less frequent evaluations of organ volumes. Our findings
      also underscore the efficacy of enzyme replacement, but raise the question of the
      need for dose reduction as nearly normal organ volumes are achieved.

PMID- 11960392
TI  - Structural rearrangements of chromosome 3 in 57 patients with acute myeloid
      leukemia: clinical, hematological and cytogenetic features.
AB  - INTRODUCTION: Structural rearrangements of chromosome 3q have been described in
      approximately 2% of patients with acute myeloid leukemia. Breakpoints are mainly
      located in the 3q21 and 3q26 regions but may occur elsewhere on chromosome 3. To
      determine the relationship between these breakpoints and the hematological
      parameters, including outcome of these patients, we analysed data from newly
      diagnosed adult AML patients with 3q rearrangements referred to our institution
      over a 15-year period. MATERIALS AND METHODS: This retrospective study was
      conducted using data from 57 AML patients (median age: 64 years, range 19-82)
      with 3q rearrangements. Cytogenetic analysis was performed using standard
      techniques (RHG banding, FISH). Data concerning AML patients with 3q
      abnormalities were compared for outcome with those from patients with normal
      karyotype and from patients with 5q deletion, treated according to the same
      intensive protocols for the same time period. RESULTS: Patients with myeloid
      malignancy displaying 3q rearrangement were assigned to five subgroups, including
      those with: 3q21/q26 rearrangement; 3q21 alone, including t(1;3)(p36;q21); 3q26
      alone, resulting in translocations involving multiple chromosome partners;
      t(3;5); 3q deletions. Among these patients, 37 were treated in AML chemotherapy
      trials. Complete remission was achieved in 43% (26/57) of cases. Five patients
      died early. Sixteen patients were resistant to induction chemotherapy. Median DFS
      and median OS were 4.5 and 8.8 months respectively. Relapse was observed in 34%
      of patients achieving CR. Comparison of the outcome of CR patients with that of
      patients presenting with normal karyotype (intermediate-risk) or complete/partial
      5q deletion (high-risk) confirmed the very poor prognosis of patients carrying 3q
      chromosomal rearrangements. CONCLUSION: These data confirm that 3q rearrangements
      at q21 or q26 are recurring chromosomal abnormalities in AML. Appearing
      frequently in combination with monosomy 7 and an abnormal megakaryopoiesis,
      patients with these abnormalities have a particularly poor prognosis.

PMID- 11960393
TI  - Cytokine release by activated T-cells in large granular lymphocytic leukemia
      associated with autoimmune disorders.
AB  - INTRODUCTION: Patients with T-cell large granular lymphocytic leukemia (T-LGLL)
      have a high incidence of autoimmune disorders. The pathogenesis of associated T
      LGLL and autoimmune abnormalities is not clear. In this study we have
      investigated the role of cytokines in the development of immune complications in
      LGLL. PATIENTS AND METHODS: We studied clinical and laboratory features of 15
      patients diagnosed with T-LGLL. The patients had various autoimmune disturbances:
      persistent neutropenia, immune thrombocytopenia, pure red-cell aplasia,
      Hashimoto's thyroiditis, sicca syndrome, systemic lupus erythemathosus, systemic
      scleroderma. The T-LGLL cells obtained from these patients were activated by
      phytohemagglutinin and incubated for 3 days. Using ELISA technique we analysed
      the release of sIL-2R, IL-4, IL-6, IL-8, IL-10, IL-12 and TNF-alpha in the
      supernatant. RESULTS: Cytokine analysis of supernatants obtained from the LGLL T
      cells stimulated with PHA revealed increased sIL-2R production in 40% (six
      patients), TNF-alpha - in 47% (seven patients), IL-6 - in 67% (10 patients), IL
      10 - in 47% (seven) and IL-8 - in 60% (nine) of patients. Levels of IL-4 and IL
      12 were not elevated compared to controls. No correlation was found between LGL
      count, CD4 versus CD8 expansion, or in the clinical findings of the patients and
      cytokine release in vitro. CONCLUSION: Our findings showing the potential of LGLL
      cells for cytokine release in vitro suggests that these cells may play a major
      role in the immune disturbances observed in large granular lymphocytic leukemia
      accompanied by autoimmunity features.

PMID- 11960394
TI  - Plasma thrombopoietin levels in patients with chronic renal failure.
AB  - INTRODUCTION: Thrombopoietin (Tpo) is the most important regulator of
      thrombocytopoiesis. The main sites of Tpo production are the liver and the kidney
      produce Tpo. In the current study, the influence of renal failure on overall Tpo
      production was evaluated. MATERIALS AND METHODS: Tpo levels were measured in 23
      patients on hemodialysis (HD) and 16 patients on chronic ambulatory peritoneal
      dialysis (CAPD). Plasma glycocalicin (GC) levels and platelet counts were
      measured as parameters of platelet mass and platelet turnover. RESULTS: Platelet
      counts were significantly lower in the HD group, both before 207+/-98 x 10(9)/l
      (P<0.001) and after hemodialysis 202+/-102 x 10(9)/l (P<0.001) when compared to
      healthy controls, 293+/-79 x 10(9)/l. No significant difference was found between
      platelet counts in patients on CAPD and healthy donors. Mean plasma Tpo levels of
      HD patients were higher both before 23+/-18 AU/ml (P<0.0001) and after dialysis
      25+/-26 AU/ml (P<0.0001), as compared to Tpo levels in healthy controls (11+/-8
      AU/ml). Patients on CAPD had significantly higher Tpo concentrations, 29+/-25
      AU/ml than healthy controls (P<0.0001). There was no difference in Tpo level
      between the HD and CAPD group. No correlation was found between Tpo concentration
      and platelet count, hematocrit, creatinine or uremia levels. The GC concentration
      was significantly higher in HD patients and CAPD patients when compared to
      healthy controls. There was no correlation between GC and Tpo level or platelet
      count. CONCLUSION: These results confirm the increased platelet turnover in
      patients with chronic renal failure. Moreover this study shows that the kidney
      does not seem to play a major role in the overall Tpo production in the body.

PMID- 11960395
TI  - The combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is
      feasible and can be an option for relapsed/refractory multiple myeloma.
AB  - INTRODUCTION: Thalidomide has recently proven to be a useful drug for treatment
      of refractory and relapsed multiple myeloma patients, up to 35% of whom achieve
      remission. However, little is known about the potential additive or synergistic
      effect upon its association with other drugs with proven efficacy in MM. MATERIAL
      AND METHODS: The present pilot study was designed to evaluate the toxicity and
      response rate of the association of thalidomide, cyclophosphamide and
      dexamethasone (ThaCyDex) in 22 refractory or relapsed MM patients. The protocol
      scheduled the administration of thalidomide at escalating doses (200 to 800
      mg/day), daily oral cyclophosphamide (CTX) (50 mg/day) and pulsed dexamethasone
      (40 mg/day, four days every three weeks). RESULTS: Adverse effects were moderate
      (grade <or=2) with only two patients in whom treatment was withdrawn due to
      neuropathy and severe somnolence. Infections were recorded in six patients, four
      requiring hospitalization for intravenous antibiotic therapy. No cases of
      thrombocytopenia grade >or=2 were noted. Other side effects included grade <or=2
      constipation (29%), somnolence (35%) or dizziness (12%). In addition, one case of
      meralgia paresthetica and one with a deep venous thrombosis were noted. Two cases
      displayed hyperglycemia and myopathy attributed to dexamethasone, which was
      solved upon changing to prednisone. With a median follow-up of 12 months, 17
      patients were evaluable for response; 13 (77%) responded to the therapy,
      including nine cases (53%) with a >50% M-component reduction (two of them with a
      complete remission). Only two responders have already progressed, with a
      projected event free survival of 51% at 12 months. Seven patients have died due
      to disease progression (n=5), sudden death (n=1) and infection (n=1). CONCLUSION:
      This study shows that ThaCyDex is a feasible and promising therapeutic approach
      for patients with relapsed/refractory MM.

PMID- 11960396
TI  - All trans retinoic acid in combination with intermediate-dose cytarabine and
      idarubicin in patients with relapsed or refractory non promyelocytic acute
      myeloid leukemia: a phase II randomized trial.
AB  - INTRODUCTION: All trans retinoic acid has shown a remarkable effectiveness in
      acute promyelocytic leukemia. These results have encouraged studies of treatment
      with ATRA in other acute myeloid leukemia subtypes. PATIENTS AND METHODS: In
      order to evaluate toxicity and antileukemic efficacy of all ATRA in patients with
      relapsed or refractory non promyelocytic AML, 95 patients (median age, 58 years;
      range, 20 to 80 years), with unclassified AML according to the FAB classification
      or secondary AML at diagnosis, or refractory or relapsing AML, received induction
      therapy with Idarubicin, 10 mg/m(2)/day, for 3 days and cytarabine, 1000
      mg/m(2)/12 h, for 6 days, alone or combined, on a randomized basis, with ATRA, 45
      mg/m(2)/day, from day 1 to complete remission. Patients in CR received
      maintenance therapy with 6 monthly courses combining Ida, 10 mg/m(2)/day,
      intravenously, on day 1 with Ara-C100 mg/m(2)/day, subcutaneously, from day 1 to
      day 5. RESULTS: Results were evaluated after one induction course. Overall 54
      patients (57%, 26 with ATRA and 28 without ATRA) achieved CR including five
      patients treated at time of initial diagnosis, seven previously resistant, 38 in
      first relapse and four in further relapse. Thirty patients (31%) had resistant
      disease and 11 (12%) died from toxicity. Median time for neutrophil recovery to
      0.5 x 10(9)/l and platelets to 20 x 10(9)/l was 31 and 21 days respectively.
      Severe toxicity (WHO grade >or=3) included infections (37%), diarrhea (9%),
      bleeding (3%), vomiting (16%), hyperbilirubinemia (5%), mucositis (6%) and
      hypercreatininemia (2%). No ATRA syndrome was noted in the ATRA arm. Median
      overall survival for the entire cohort was 6.3 months and median disease-free
      survival was 4.7 months. There were no statistical differences in terms of CR,
      DFS, and OS between the two arms. CONCLUSION: We conclude that ATRA in
      combination with Ida and Ara-C can be administered safely to high-risk AML
      patients. However, in this setting, ATRA did not offer any advantage when
      compared to chemotherapy alone.

PMID- 11960397
TI  - Patterns of mortality in sickle cell disease in adults in France and England.
AB  - INTRODUCTION: An understanding of the causes of death among patients with sickle
      cell disease may be informative for both epidemiology and pathogenesis. This
      information should aid anticipation of dangerous clinical conditions, counselling
      patients and design of preventive therapies. PATIENTS AND METHODS: All deaths
      known to four European sickle cell disease centres over a 10-year period were
      retrospectively analysed. The circumstances of death were classified as follows:
      (1) acute sickle related vaso-occlusion; (2) chronic organ failure related to
      sickle cell disease; (3) infection; and (4) miscellaneous causes. RESULTS: Sixty
      one adult patients (mean age: 32+/-11 years) died during the study period. Twelve
      patients suddenly died at home; most of them exhibited symptoms of vaso-occlusion
      but in eight patients, the cause of death was unknown. The primary cause of death
      in the 53 evaluable patients was sickle related vaso-occlusion (27 out of 53;
      51%) which manifested mainly by acute multiorgan failure (n=13) and acute chest
      syndrome (n=9). Ten of the 27 patients (37%) who died in these circumstances had
      an apparent mild disease before their deaths. Ten patients (19%) died of
      documented infection. Ten of the evaluable patients (19%) died of a chronic
      terminal visceral involvement related to sickle cell disease which was mainly
      liver cirrhosis. Four patients died by suicide or because of refusal of care and
      two patients died of iatrogenic complication. CONCLUSION: The primary cause of
      death in adults appears to be vaso-occlusive, even in patients with no overt
      organ-system failure. Our results emphasise that the circumstances of death in
      sickle cell disease are different between adults and children. The deaths among
      adults appear not to be easily assigned to a few preventable causes as they are
      in children.

PMID- 11960398
TI  - Sustained complete remission of chronic refractory immune thrombocytopenic
      purpura (ITP) of 10 years duration after only two infusions of rituximab.

PMID- 11960400
TI  - [Interventional radiology - When united the weak are also strong].

PMID- 11960401
TI  - [Organ-sparing surgery of renal cell carcinoma - operative technique and findings
      in radiological follow-up].
AB  - Nephron-sparing surgery of renal cell carcinoma in the 1970's and 1980's in
      patients with bilateral renal tumors or reduced renal function (imperative
      indication) has shown a very low risk of recurrent cancer. Today, nephron-sparing
      surgery in renal cell carcinoma is considered in an increasing number of patients
      with expected sufficient renal function after nephrectomy (elective indication).
      Resection technique, the use of Tabotamp(R) to reduce bleeding, and pseudotumors
      do complicate the interpretation of the images. It has been not yet defined which
      diagnostic modality is best suited for follow-up after renal cell carcinoma
      resection. Follow-up protocols in different institutions show a wide variety. The
      follow-up of patients after nephron-sparing surgery is performed by annual
      sonography or MRI every three months. Up to now, CT and ultrasound are the
      standard methods. MRI with its multiplanar imaging and improved soft tissue
      contrast seems to have an equal diagnostic value. Additionally, MRI seems to be
      suited for patients with reduced renal function. The aim of this paper is to give
      guidelines for the radiologist to understand the different surgical procedures
      and to evaluate the postoperative findings. Different imaging modalities in the
      follow-up of patients and special radiological phenomena are discussed.

PMID- 11960403
TI  - [Image quality of paper prints compared to film copies in CT investigations].
AB  - PURPOSE: Evaluation of image quality of paper prints in routine CT
      investigations. METHOD: The image quality of paper prints from 104 CT scans of
      daily routine investigations was analysed by three observer three observers
      according to a five-point ranking scale for contrast, grey level, spatial
      resolution, and subjective confidence in correct evaluation. Each study was rated
      "acceptable" or "not acceptable for documentation". RESULTS: In 312 ratings the
      mean grade for contrast was 2.7, for grey levels 3.2, and for spatial resolution
      3.3. Grades ranged from 1 = very good to 5 = insufficient. Subjective confidence
      in correct evaluation was rated as "certain" in 77.4 %, "likely" in 18.4 % and
      "impossible to evaluate" in 4.2 % of cases. 93.7 % of printed CT images were
      rated "acceptable for documentation". CONCLUSION: Image quality of paper prints
      does not reach the quality of laser films concerning its contrast, grey levels,
      and spatial resolution. Nevertheless, paper prints are acceptable for
      documentation of findings in most CT investigations. A high confidence in correct
      evaluation was found. Limitations are found in documentation of small coin
      lesions of the lung and ischemic lesions of the neurocranium.

PMID- 11960402
TI  - [Alar ligaments: radiological aspects in the diagnosis of patients with whiplash
      injuries].
AB  - Post-traumatic changes of the alar ligaments have been proposed to be the cause
      of chronic pain in patients after whiplash injury of the cervical spine. In
      addition to an asymmetric dens position, widening of the atlantodental distance
      to more than 12 mm can be an indirect sign of an alar ligament rupture. CT is
      recommended for detection of a avulsion fracture of the occipital condyle.
      Isolated ruptures of the alar ligaments are best visualized on MRI. In patients
      with chronic impairments after whiplash injuries changes of the alar ligaments on
      MRI must be differentiated from normal variants in healthy individuals.

PMID- 11960404
TI  - [The prognostic value of quantified MRI at an early stage of Bell's palsy].
AB  - OBJECTIVE: The aim of the study was to assess whether MRI has a prognostic value
      at an early stage of Bell's palsy. MATERIAL AND METHODS: Prospective, blinded
      study on 30 patients suffering from Bell's palsy, who came to hospital until the
      sixth day of illness, to receive high doses steroid therapy. MRI was done on the
      first day of inpatient treatment as a gradient-echo-sequence with a slice
      thickness of 0.7 mm before and after i. v. administration of 0.1 mmol GdDTPA/kg
      weight. The signal intensity increase was evaluated quantitatively by region on
      interest (ROI). The results were compared to the clinical outcome and the results
      of electrophysiology. RESULTS: The examinations of all patients could be
      evaluated. The 3 patients who developed a chronic facial paralysis were detected
      by MRI on the first day of inpatient treatment. The patients, who showed MR signs
      for an unfavorable course, had a highly significant pathologic compound muscle
      action potential (CMAP) as a result of the electrophysiologic measurement. Rather
      than using complex measurement procedures it is possible to obtain reliable
      prognostic information from just one measurement within the Internal auditory
      canal before and after i. v. administration of contrast. CONCLUSION: MRI has a
      prognostic value at an early stage of the illness. In the clinical setting this
      measurement is easy to perform, so that it is possible to obtain prognostic
      information at a stage when causal treatment is still possible.

PMID- 11960405
TI  - [Is a dynamic MRI examination of the pancreas still necessary?].
AB  - PURPOSE: Evaluation of the diagnostic potential of a dynamic MR examination of
      the pancreas. MATERIAL AND METHODS: Retrospective study on 49 patients who
      underwent MRI of the pancreas (2 insulinomas, 2 cystadenomas, 19 pancreatic
      carcinomas, 26 patients with chronic pancreatitis). Interpretation was done in
      two steps: Initial evaluation of T2-weighted TSE-sequences, T1-weighted gradient
      echo sequences before and after injection of Gadolinium-DTPA i. v. Afterwards,
      additional evaluation of a dynamic contrast-enhanced MRI series of the pancreas
      with four dynamic scans. RESULT: Dynamic MR examination of the pancreas is useful
      in case of insulinomas. However, in case of pancreatic cancer an additional
      dynamic MR examination of the pancreas does not provide further clinically
      relevant information. CONCLUSION: In patients with a suspicion of pancreatic
      cancer, the injection of contrast material should preferably be used for the
      performance of a contrast-enhanced MR angiography at the expense of a dynamic MR
      examination.

PMID- 11960406
TI  - [Diagnostic value of secretin injections in dynamic MR pancreatography].
AB  - PURPOSE: To evaluate the effect of intravenous injections of secretin during MRP
      procedures. MATERIAL AND METHODS: From 1998 to 2001, 340 patients were examined
      with MRP. Depending on the native MRI/MRP diagnosis, 110 of them received an
      injection of secretin followed by multiple MRP's (every 2 minutes) up to 10 min
      after injection. Diagnosis included healthy persons (n = 23), pancreas divisum (n
      = 11), chronic pancreatitis (n = 68), and pancreatic tumors (n = 22); some
      patients had more than 1 diagnosis. Visibility of duct structures and amount of
      fluid filling of the duodenum after secretin injection were evaluated (dynamic
      examination) based on a five-point scale. Differences were tested statistically
      by means of Mc Nemar's test and ROC analysis. RESULTS: The visibility of the
      pancreatic duct could be increased significantly after secretin injection in all
      subgroups (p < 0.05). Statistically, it turned out not to be important at what
      time point after injection the MRP was taken. It was possible to evaluate the
      excretion rate of the pancreas. In healthy persons and those with pancreas
      divisum, the fluid filling of the duodenum was significantly higher than in those
      with chronic pancreatitis or pancreatic tumors. However, this finding alone did
      not suffice in differentiating between both groups (sensitivity 0.68 and
      specificity 0.59, respectively). CONCLUSION: The i. v. injection of secretin
      improves the ability of MRP to evaluate the pancreas by increasing the visibility
      of the pancreatic duct structures and provides a method to assess the excretion
      rate of the gland.

PMID- 11960407
TI  - [Selective CT mesentericography in the diagnostics of obscure overt intestinal
      bleeding: preliminary results].
AB  - AIM: To evaluate intra-arterial CT mesentericography (CTM) in the diagnostics of
      severe obscure overt intestinal bleeding in comparison with conventional
      mesentericography (MG) and surgery. METHODS: In 8 patients (23 - 82 years, mean
      59 years), CTM was performed via the catheter left in the superior mesenteric
      artery after MG to detect the source of bleeding. Early and late-phase spiral CT
      scans were acquired after administration of contrast medium. Active bleeding was
      considered to be present if extravasation of contrast medium into the bowel was
      found. The results of MG and CTM were compared with the results of surgery.
      RESULTS: With MG active bleeding was found in one patient, with CTM in five
      patients. In three patients, both MG and CTM were negative. Six patients
      underwent surgery. Five cases of bleeding detected with CTM were confirmed by
      surgery. In one case, bleeding found with CTM was not confirmed by surgery. One
      patient underwent surgery although all imaging procedures were negative. The
      source of bleeding remained unknown. Surgically, the site of bleeding was located
      in the jejunum in 3 patients (jejunitis, jejunal ulcers, carcinoid), one patient
      had a diverticulum in the ascending colon. The colonic bleeding site was
      correctly localized with CTM, whereas the small bowel bleeding could only roughly
      be assigned to the proximal or distal jejunum or jejunoileal transition area.
      CONCLUSION: Preliminary results indicate that selective CTM is superior to MG in
      the evaluation of severe obscure overt intestinal bleeding.

PMID- 11960408
TI  - [The value of different spiral CT phases in the detection of liver metastases].
AB  - PURPOSE: To assess the value of the non-contrast phase (NCP), hepatic-arterial
      phase (HAP) and portal-venous phases (PVP) for the detection of liver metastases
      by spiral CT. METHODS: In order to detect liver metastases, 119 patients (58
      women, 61 men; mean age: 62 years) underwent triphasic spiral CT (8 mm
      collimation, 12 mm table increment/rotation, 7 mm reconstruction increment). NCP,
      HAP (20 s delay) and PVP (70 s delay) scans were acquired (contrast medium
      injection rate: 4 ml/s). CT analysis comprised independent evaluation of the
      three scan series for detection and conspicuity of liver metastases (conspicuity
      score: 0 = not visible, 1 = barely visible, 2 = clearly visible, 3 = distinctly
      visible). RESULTS: In 83 of the 119 patients, 478 liver metastases were detected
      (110 hypervascular and 368 hypovascular lesions). 285 (60 %) metastases were
      detected on NCP scans. Significantly more lesions were seen on HAP (n = 375, 78
      %) and on PVP (n = 428, 90 %). No lesion was detected on NCP studies alone. For
      all detected metastases, mean conspicuity was 1.2 +/- 0.4 on NCP, 1.8 +/- 0.8 on
      HAP and 2.2 +/- 0.8 PVP. Hypervascular lesions were best seen on HAP with a
      conspicuity score of 2.0 +/- 0.8 versus 1.3 +/- 0.5 on NCP and 1.5 +/- 0.8 on
      PVP. Hypovascular lesions reached the highest conspicuity on PVP with 2.4 +/- 0.8
      versus 1.2 +/- 0.4 on NCP and 1.7 +/- 0.7 on HAP. CONCLUSION: For detection of
      liver metastases with spiral CT, contrast series seem to be sufficient. For
      tumors likely to seed hypervascular metastases, HAP scans should be applied in
      addition to the PVP.

PMID- 11960409
TI  - [Submillimeter 3D coronary MR angiography with real-time navigator correction in
      107 patients with suspected coronary artery disease].
AB  - PURPOSE: To evaluate the clinical value of high-resolution coronary MR
      angiography (coronary MRA) in a large group of patients with suspected coronary
      artery disease. METHODS AND MATERIAL: 107 patients with suspected coronary artery
      disease underwent free-breathing coronary MRA (Intera, 1.5 T, Philips Medical
      Systems). To compensate for artefacts due to respiratory motion, a right
      hemidiaphragmatic navigator with real time-time slice correction was used. An ECG
      gated, fat-suppressed, 3D segmented-k-space gradient echo sequence (in plane
      resolution 0.70 x 0.79 mm(2)) was used. Cardiac catheterization with selective
      coronary angiography was performed in all patients. Visualization of the coronary
      arteries (CA) was qualitatively assessed using a four-point grading scale.
      RESULTS: Image quality of grade 1 was achieved in 24 %, grade 2 in 48 %, grade 3
      in 24 % and grade in in 4 % of patients. Based on an evaluation of the coronary
      MRAs of all patients (n = 107) sensitivity and specificity for the detection of
      stenoses > 60 % in the proximal and middle main coronary arteries were 74 % and
      63 %, respectively. In coronary MRAs with good quality [grade 1 and 2, n = 77/107
      (72 %)] sensitivity and specificity for the detection of coronary stenoses were
      88 % and 91 %, respectively. CONCLUSION: Submillimeter 3D coronary MRA with real
      time navigator correction allows high quality imaging of the proximal and middle
      main coronary arteries with good sensitivity and specificity for detection of
      stenoses > 50 % in selected patients. However, in about 28 % of patients image
      quality is severely impaired.

PMID- 11960410
TI  - [Morphologic and functional assessment of vascular abnormalities of the pulmonary
      vasculature by breath-hold MR techniques].
AB  - PURPOSE: To evaluate breath-hold MR techniques for morphologic and functional
      assessment of vascular abnormalities of the pulmonary vasculature. PATIENTS AND
      METHODS: 13 patients aged 11 to 60 years with different vascular abnormalities of
      the pulmonary vasculature (5 patients with 16 arteriovenous malformations, 8
      patients with partial anomalous pulmonary venous return) underwent MR imaging at
      1.5 T. For morphological assessment, a contrast-enhanced 3D MR angiography (ce
      MRA) was performed after a timing run. Segmented cine- and velocity-encoded GRE
      sequences were used for delineation of associated cardiac septal defects and for
      determination of systemic left-to-right or intrapulmonary shunt volumes.
      Selective intra arterial digital subtraction angiography, cardiac
      catheterization, and the intraoperative situs served as reference standards.
      RESULTS: Ce-MRA allowed for detection of all vascular abnormalities and for
      anatomic characterization of 14/16 arteriovenous malformations. Flow measurements
      in the feeding arteries allowed for determination of intrapulmonary shunt volumes
      in 4/5 patients. Flow measurements performed in the pulmonary arteries and the
      ascending aorta enabled determination of systemic left-to-right shunting in
      patients with anomalous pulmonary venous return. Cine-sequences clearly depicted
      associated cardiac septal defects. CONCLUSION: Breath-hold MR techniques allow
      for morphological and functional characterization of vascular anomalies of the
      pulmonary vasculature. Therefore, they are the non-invasive method of choice for
      planning further treatment.

PMID- 11960411
TI  - [Chronic thromboembolic pulmonary hypertension: diagnostic impact of Multislice
      CT and selective Pulmonary-DSA].
AB  - PURPOSE: To evaluate the diagnostic impact of multislice-CT and selective
      pulmonary DSA in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS:
      994 vessel segments of 14 consecutive patients with CTEPH were investigated with
      multislice-CT (slice thickness 3 mm, collimation 2.5 mm, reconstruction intervall
      2 mm) and selective pulmonary DSA (posterior-anterior, 45 degrees oblique, and
      lateral projection. Analysis was performed by 2 investigators independently for
      CT and DSA. Diagnostic criteria were occlusions and non-occlusive changes like
      webs and bands, irregularities of the vessel wall, diameter reduction and
      thromboembolic depositions at different levels from central pulmonary arteries to
      subsegmental arteries. Reference diagnosis was made by synopsis of CT and DSA by
      consensus. RESULTS: Concerning patency CT and DSA showed concordant findings
      overall in 88.9 %, 92.9 % for segmental arteries and 85.4 % for subsegmental
      arteries. Concerning any thromboembolic changes, multislice-CT was significantly
      inferior to selective DSA (concordance 67.0 % overall, 70.4 % for segments and
      63.6 % for subsegments). Non-occlusive changes of the vessels were significantly
      underdiagnosed by CT (concordance of CT versus DSA: 23.1 %). CONCLUSION:
      Multislice-CT and selective pulmonary DSA are equivalent for diagnosis of vessel
      occlusions at the level of segmental and subsegmental arteries. However, for
      visualisation of the non-occlusive thromboembolic changes of the vessel wall
      selective pulmonary DSA is still superior compared to multislice-CT. Multislice
      CT and selective pulmonary DSA are complementary tools for diagnosis and
      treatment planning of chronic thromboembolic pulmonary hypertension (CTEPH).

PMID- 11960412
TI  - [CT-guided sympathicolysis in peripheral artery disease - Indications, patient
      selection and long-term results].
AB  - PURPOSE: Assessment of long-term results of CT-guided lumbar sympathicolysis
      (LSL) in advanced peripheral arterial vascular disease (pavd). Establishment of a
      suitable patient selection. PATIENTS AND METHODS: LSL was performed in 138 cases
      with Fontaine stages III (13 %) and IV (87 %). 250 consecutive patients were
      examined with a radionuclide perfusion study of the feet prior to and during
      peridural anaesthesia (PDA) in order to select suitable patients for LSL. LSL was
      not performed in patients with impaired perfusion under PDA (n = 112). Early and
      long-term results after one to five years were evaluated. RESULTS: In 79 % an
      initial improvement was found after LSL. After more than one year success was
      established in 38 %. 49 % of the cases had a progression of the disease. This is
      significantly better compared to a control group with conservative treatment and
      an initial improvement of 36 %. After more than one year only12 % revealed an
      improvement. In 82 % the disease was progressive. Diabetics showed also a
      positive response to LSL. CONCLUSION: LSL has a positive influence on the course
      of pvad in patients selected by radionuclide perfusion studies. Diabetes and
      angiographic findings do not play any first role in patient selection for LSL.

PMID- 11960414
TI  - [MR imaging of gastric wall layers in vitro: correlation to thehistologic wall
      structure].
AB  - PURPOSE: To correlate gastric wall layers visible of MRI with the anatomical
      structure of the gastric wall. METHODS: After macroscopic preparation 5 x 5 cm
      post-mortem tissue sections of the gastric antrum were evaluated using a 2.4
      Tesla MR unit (Bruker, Ettlingen, Germany). MR imaging consisted of T2-weighted
      multi-spinecho sequences in longitudinal and axial directions. The specimens then
      were stained with hematoxylin-eosin for histological examination. After that
      histological correlation of the gastric wall layers visible on MRI was performed.
      RESULTS: In all specimens four gastric wall layers could be clearly identified on
      MRI. The direct comparison of those layers to the histological findings showed
      the following correlation: 1) intermediate signal = mucosa, 2) hypointense signal
      = lamina muscularis mucosae, 3) hyperintense signal = submucosa, 4) intermediate
      signal = muscularis propria. CONCLUSIONS: Gastric wall layers visible on MRI were
      successfully correlated to the anatomic layers of the gastric wall. This allows
      us for the first time to classify invasion of gastric carcinoma using high
      spatial-resolution MR imaging. However, the subserosa and serosa are excluded
      from this conclusion, because so far a reliable statement concerning the value of
      MRI to depict these very variable layers is not possible.

PMID- 11960413
TI  - [Endovascular implantation of stent-grafts in the thoracic aorta -mid-term
      results of a prospective controlled study].
AB  - PURPOSE: To evaluate the effectiveness and safety of endovascular treatment of
      various descending thoracic aortic pathologies with covered stent-grafts as an
      alternative to open surgery. METHODS: Among 16 patients (5 type B dissections, 5
      contained ruptures, 3 aneurysms of the descending aorta, 1 thoraco-abdominal
      aneurysm, 1 mural thrombosis, 1 patch aneurysm) treated between November 1997 and
      November 2000, eight patients received Talent stent-grafts and another 8 patients
      underwent a Gore-TAG stent-graft implantation. A clinical follow-up and control
      CT scans were obtained after the procedure and then at six-month intervals.
      RESULTS: Deployment of the stent-grafts was technically successful in all cases.
      Sufficient aortic reconstruction was achieved in all but one patient who needed
      surgical treatment. One patient died two days after the procedure from aortic
      rupture due to retrograde type A dissection. Another patient died 19 months after
      the procedure from an unknown cause. There was no occurrence of distal
      embolization, paralysis or infection. During follow-up, all patients remained
      free from recurrence or late complications of their disease. CONCLUSION:
      Endoluminal treatment of thoracic aortic pathologies with covered stent-grafts
      appears to be a safe and feasible method with at least mid-term efficacy.

PMID- 11960415
TI  - [Radiology of atlanto-occipital subluxation].

PMID- 11960416
TI  - [Schistosoma mansoni--involvement of the liver. Diagnosis by magnetic resonance
      tomography (MRT)].

PMID- 11960417
TI  - [Hyperdense areal in the putamen after intra-arterial medialysis: contrast media
      extravasation or hemorrhage?].

PMID- 11960418
TI  - [Concerning the commentary by J. Blobel (Fortschr Rontgenstr 2001; 173: rubric
      Medicine and Market].

PMID- 11960419
TI  - [Cost-effectiveness analysis of preoperative MR mammography in suspect breast
      lesions].

PMID- 11960420
TI  - Contrasting copper-dioxygen chemistry arising from alike tridentate alkyltriamine
      copper(I) complexes.
AB  - Copper(I)-dioxygen interactions are of great interest due to their role in
      biological O2-processing as well as their importance in industrial oxidation
      processes. We describe here the study of systems which lead to new insights
      concerning the factors which govern Cu(II)-mu-eta2:eta2 (side-on) peroxo versus
      Cu(III)-bis-mu-oxo species formation. Drastic differences in O2-reactivity of
      Cu(I) complexes which differ only by a single -CH3 versus -H substituent on the
      central amine of the tridentate ligands employed are observed. [Cu(MeAN)]B(C6F5)4
      (1) (MeAN = N,N,N',N',N'-pentamethyl-dipropylenetriamine) reacts with O2 at -80
      degrees C to form almost exclusively the side-on peroxo complex
      [{CuII(MeAN)}2(O2)]2+ (3) in CH2Cl2, tetrahydrofuran, acetone, and diethyl ether
      solvents, as characterized by UV-vis and resonance Raman spectroscopies. In sharp
      contrast, [Cu(AN)]B(C6F5)4 (2) (AN = 3, 3'-iminobis(N,N-dimethyl-propylamine) can
      support either Cu2O2 structures in a strongly solvent-dependent manner. Extreme
      behavior is observed in CH2Cl2 solvent, where 1 reacts with O2 giving 3, while 2
      forms exclusively the bis-mu-oxo species [{CuIII(AN)}2(O)2]2+ (4Oxo). Stopped
      flow kinetics measurements also reveal significant variations in the oxygenation
      reactions of 1 versus 2, including the observations that 4Oxo forms much faster
      than does 3; the former decomposes quickly, while the latter is quite stable at
      193 K. The solvent-dependence of the bis-mu-oxo versus side-on peroxo preference
      observed for 2 is opposite to that reported for other known copper(I) complexes;
      the factors which may be responsible for the unusual behavior of 1/O2 versus 2/O2
      (possibly N-H hydrogen bonding in the AN chemistry) are suggested. The factors
      which affect bis-mu-oxo versus side-on peroxo formation continue to be of
      interest.

PMID- 11960421
TI  - Crystallographic characterization of the structure of the endohedral fullerene
      [Er2@C82 isomer I] with C(s) cage symmetry and multiple sites for erbium along a
      band of ten contiguous hexagons.
AB  - The structure of one of the three previously separated isomers of {Er2@C82} has
      been determined through a single-crystal X-ray structure determination of the
      noncovalent adduct, {Er2@C82 Isomer I}.{CoII(OEP)}.1.4(C6H6).0.3(CHCl3). The C82
      cage is identified specificlly as the Cs(82:6) isomer (one of nine possible
      isolated pentagon isomers) from the crystallographic data. The carbon atoms of
      the C82 cage were individually identified and refined with only a constraint that
      required the two halves of the cage to possess similar bond lengths. Although the
      carbon cage is well ordered at 113 K, the erbium atoms are disordered. The
      electron density within the cage of {Er2@C82 Isomer I} has been modeled with two
      major sites with occupancies of 0.35 and 21 other individual erbium sites with
      occupancies ranging from 0.138 to 0.011. These erbium sites all reside near the
      walls of the fullerence and cluster near a band of ten contiguous hexagons that
      encircles the carbon cage. Since two other isomers of C82 (C3v(82:8) and
      C2v(82:9)) have a similar band of ten contiguous hexagons, it is tempting to
      speculate that the other two known isomers of {Er2@C82} have these cage
      structures.

PMID- 11960422
TI  - Reversing a rotaxane recognition motif: threading oligoethylene glycol
      derivatives through a dicationic cyclophane.
AB  - An already well-established recognition motif-namely one in which the NH2+
      centers in the rod sections of the dumbbell components of rotaxanes are encircled
      by macrocyclic polyether components-has been turned simultaneously outside-in and
      inside-out, a fact that has been proved beyond any doubt by the stoppering of
      both ends of a [2]pseudorotaxane to give a stable [2]rotaxane. The
      [2]pseudorotaxane is formed in nitromethane when a benzylic dibromide, obtained
      after reacting an excess of 1,4-bis(bromomethyl)benzene with hexaethylene glycol,
      is added to an equimolar amount of a dicationic cyclophane in which two -CH2OCH2-
      chains link a pair of dibenzylammonium ions through the para positions on their
      phenyl rings. When the [2]pseudorotaxane is reacted in nitromethane with
      triphenylphosphine, a [2]rotaxane and the corresponding free dumbbell compound
      are isolated in 58 and 31% yields, respectively. The structure of the [2]rotaxane
      is established by using mass spectrometry (FABMS and ESMS) and NMR (1H and 13C)
      spectroscopy in nitromethane-d3. The [2]rotaxane exhibits quite dramatic changes
      in the 1H chemical shifts of the signals for its CH2N+ and CH2O protons compared
      with those in the free dumbbell compound. The 1H NMR spectrum of the
      [2]pseudorotaxane shows many similar features. Titration experiments with three
      of the six different CH2O probes give an average Ka value of 2900 +/- 750 M-1 in
      nitromethane-d3. The new recognition motif for the template-directed synthesis of
      rotaxanes can now be exploited at both the molecular and macromolecular levels of
      structure with numerous potential applications in sight.

PMID- 11960423
TI  - Identification of a set of genes involved in the formation of the substrate for
      the incorporation of the unusual "glycolate" chain extension unit in ansamitocin
      biosynthesis.
AB  - The unusual "glycolate" extender unit at C-9/C-10 of ansamitocin is not derived
      from 2-hydroxymalonyl-CoA or 2-methoxymalonyl-CoA, as demonstrated by feeding
      experiments with the corresponding 1-13C-labeled N-acetylcysteamine thioesters
      but is formed from an acyl carrier protein (ACP)-bound substrate, possibly 2
      methoxymalonyl-ACP, elaborated by enzymes encoded by a subcluster of five genes,
      asm12-17, from the ansamitocin bisosynthetic gene cluster.

PMID- 11960424
TI  - An unusual ruthenium-catalyzed cycloisomerization of alkynes and propargyl
      alcohols.
AB  - CpRu(NCCH3)3+PF6- catalyzes the cycloisomerization of diyne-ols to
      alpha,beta,gamma,delta-unsaturated aldehydes and ketones in good-to-excellent
      yields. 1-Hydroxy-2,7-diynes and 1-hydroxy-2,8-diynes can be utilized to form
      highly functionalized five- and six-membered rings, respectively. Tertiary as
      well as secondary propargyl alcohols are cycloisomerized to a single isomeric
      product. A wide variety of tether substitution can be tolerated. Even totally
      unsubstituted tethers can be employed, as geminal disubstituents are not required
      for cyclization. Additional hydroxyl substituents at an alternative "internal"
      propargylic position are eliminated during the reaction-a feature that leads to a
      convenient cyclopentadiene synthesis. Furthermore, 3-hydroxy-1,6-diynes also can
      be cyclized to form cross-conjugated aldehydes.

PMID- 11960425
TI  - Amphotericin B covalent dimers forming sterol-dependent ion-permeable membrane
      channels.
AB  - Polyenemacrolides such as amphotericin B (AmB) were thought to assemble together
      and form an ion channel across plasma membranes. Their antimicrobial activity has
      been accounted for by this assemblage, whose stability and activity are dependent
      on sterol constituents of lipid bilayer membranes. The structure of this channel
      like assemblage formed in biomembranes has been a target of extensive
      investigations for a long time. For the first step to this goal, we prepared
      several AmB dimers with various linkers and tested for their channel-forming
      activity. Among these, AmB dimers that bore an aminoalkyl-dicarboxylate tether
      covalently linked between amino groups of AmB showed potent hemolytic activity.
      Furthermore, K+ influx actions monitored by measuring the pH of the liposome
      lumen by 31P NMR revealed that the dimers formed the molecular assemblage similar
      to that of AmB in phospholipid membrane. Judging from changes in 31P NMR spectra,
      the dimers appeared to induce "all-or-none"-type ion flux across the liposome
      membrane in the presence of ergosterol, which suggested that the ion channel
      formed by ergosterol/dimer is similar to that of AmB. With these data in hand, we
      are now trying to elucidate the structure of the ion-channel complex by making
      the labeled conjugates of AmB for NMR measurements.

PMID- 11960426
TI  - Thiophene and butadiene-thiolate complexes of molybdenum: observations relevant
      to the mechanism of hydrodesulfurization.
AB  - Mo(PMe3)6 reacts with thiophene to give the eta5-thiophene complex (eta5
      C4H4S)Mo(PMe3)3 and the eta5-butadiene-thiolate complex (eta5
      C4H5S)Mo(PMe3)2(eta2-CH2PMe2), which are the first examples of (i) eta5-thiophene
      coordination and (ii) C-S cleavage and hydrogenation by a molybdenum compound.
      Deuterium labeling studies suggest that the hydrogenation of thiophene may
      involve an alkylidene intermediate, an observation that has ramifications for the
      mechanisms of hydrodesulfurization.

PMID- 11960427
TI  - A pi-stacking terthiophene-based quinodimethane is an n-channel conductor in a
      thin film transistor.
AB  - A terthiophene-based quinodimethane, 3',4'-dibutyl-5,5' '-bis(dicyanomethylene)
      5,5' '-dihydro-2,2':5',2' '-terthiophene (1) was synthesized and crystallized.
      Compound 1 has a planar quinoid geometry that is stabilized by dicyanomethylene
      groups at each end of the molecule. In the crystal each molecule is part of a
      dimerized face-to-face pi-stack, with intermolecular spacings of 3.47 and 3.63 A,
      respectively. Cyclic voltammetry showed that 1 could be reversibly reduced and
      oxidized in methylene chloride solution. Thin film transistors (TFTs) were
      prepared by vacuum evaporation of 1 onto SiO2(300 nm)/Si substrates, followed by
      evaporation of Ag source and drain contacts. The doped Si substrate served as the
      gate electrode. X-ray diffraction and atomic force microscopy indicate the films
      are polycrystalline, with the long axes of the molecules approximately
      perpendicular to the substrate. The TFT measurements revealed n-channel
      conduction in films of 1, with room-temperature electron field effect mobilities
      as high as 0.005 cm2/Vs. The butyl side chains give 1 appreciable solubility in a
      range of common solvents, and preliminary TFT results on films cast from
      chlorobenzene show electron mobility as high as 0.002 cm2/Vs. These results
      indicate that pi-stacked quinoidal thiophene oligomers are a promising new class
      of soluble n-channel organic semiconductors.

PMID- 11960428
TI  - Halophilic reactions of a stable silylene with chloro and bromocarbons.
AB  - A number of disilanes have been synthesized from a stable silylene, 1 (N,N'-di
      tert-butyl-1,3-diaza-2-silacyclopent-4-en-2-ylidene), and a variety of
      halocarbons. It is proposed that disilane formation is a result of an initial
      halophilic interaction between the silylene and halocarbon. Formation of
      disilanes from 1 and CCl4, 2a, CHCl3, 2b, CH2Cl2, 2c, benzyl chloride, 2d, and
      bromobenzene, 5, are described here. An X-ray crystal structure of 2b was
      determined.

PMID- 11960429
TI  - Cyclocopolymerization: a mechanistic probe for dual-site alternating
      copolymerization of ethylene and alpha-olefins.
AB  - The copolymerization of ethylene with 1,5-hexadiene or 1-hexene was studied with
      the series of ansa-metallocenes Me2Si(Cp)(9-Flu)ZrCl2 (1), Me2Si(1-Ind)(9
      Flu)ZrCl2 (3), and Me2Si(9-Flu)2ZrCl2 (4). 1,5-Hexadiene, a monomer which
      requires two insertion events to be cyclopolymerized, when copolymerized with
      ethylene using 3/MAO, gave a copolymer with a novel architecture. When compared
      with the copolymerization of 1-hexene with ethylene, the observed striking
      differences between the two copolymers provided compelling evidence for a dual
      site alternating copolymerization mechanism in both cases. The copolymerization
      results from 1/MAO and 4/MAO further support this.

PMID- 11960430
TI  - Individually addressable submicron scale light-emitting devices based on
      electroluminescence of solid Ru(bpy)3(ClO4)2 films.
AB  - A submicron light-emitting device (LED) was fabricated from lithographically
      fabricated parallel indium-tin oxide (ITO) finger electrodes (0.9 mum wide)
      separated by a 1.1 mum gap. A single layer of an amorphous (a) Ru(bpy)3(ClO4)2
      film ( approximately 100 nm thick) was spin-coated on the electrode array. Ga:In
      or carbon paste was employed as a liftable upper contact electrode. Films (
      approximately 1.5 mum thick) of single-crystal Ru(bpy)3(ClO4)2 (xyl) between two
      ITO electrodes in a sandwich cell were also prepared and produce
      electroluminescence. As with larger cells of this type, the high-resolution
      electroluminescence produced showed a high external efficiency ( approximately
      3.4%), a low turn-on voltage (2.3 V), and reasonable stability. The single
      crystal cells also behaved as photovoltaic devices and a short-circuit
      photocurrent was observed when they were irradiated without a bias voltage.

PMID- 11960431
TI  - Carbon-carbon bond activation of R-CN (R = Me, Ar, iPr, tBu) using a cationic
      Rh(III) complex.
AB  - Addition of 1.0 equiv of Ph3SiH to [Cp*(PMe3)Rh(Me)(CH2Cl2)]+BAr'4- (1) resulted
      in release of methane and quantitative formation of
      [Cp*(PMe3)Rh(SiPh3)(CH2Cl2)]+BAr'4- (2). Subsequent addition of 1.0 equiv of MeCN
      to 2 caused immediate displacement of dichloromethane to form the eta1-nitrile
      adduct [Cp*(PMe3)Rh(SiPh3)(NCMe)]+BAr'4- (3). Upon standing at room-temperature
      overnight, complex 3 converted quantitatively to another product which has been
      characterized as the C-C activation product, [Cp*(PMe3)Rh(Me)(CNSiPh3)]+BAr'4-
      (5). Addition of other nitrile substrates (R-CN, R = Ph, (4-CF3)Ph, (4-MeO)Ph,
      iPr, tBu) to 2 also resulted in C-C activation of the R-CN bond to form
      [Cp*(PMe3)Rh(R)(CNSiPh3)]+BAr'4-. Evidence for an eta2-iminoacyl intermediate
      complex, [Cp*(PMe3)Rh(eta2-C(R)=N(SiPh3)]+BAr'4-, is also presented.

PMID- 11960432
TI  - A photoactivated precipiton for reagent sequestration in solution-phase
      synthesis.
AB  - Precipitons are molecular phase tags for chemical separations. They can be
      switched from a high-solubility to a low-solubility state to facilitate product,
      reagent, or catalyst isolation. This paper presents the first photoactivated
      precipiton and demonstrates that this precipiton is an efficient amine scavenging
      agent in solution-phase syntheses of amides, ureas, and imines. This approach to
      amine scavenging offers advantages over solid-phase scavenging methods. The amine
      is captured in a homogeneous medium, so the capture is much faster than seen with
      isocyanate resins, and only a small excess of the scavenger is required.

PMID- 11960433
TI  - Evidence for a strong hydrogen bond in the catalytic dyad of transition-state
      analogue inhibitor complexes of chymotrypsin from proton-triton NMR isotope
      shifts.
AB  - We present here the first accurate measurements of 1H (H) versus 3H (T) isotope
      shift (DeltadeltaT-H = deltaT - deltaH) in a protein. This approach was used to
      investigate the strength of the hydrogen bond between His57 and Asp102 in the
      catalytic dyad of chymotrypsin in three transition-state analogue inhibited
      complexes: N-acetyl-l-phenylalanyl trifluoromethyl ketone (N-AcF-CF3), N-acetyl-l
      valyl-l-phenylalanyl trifluoromethyl ketone (N-AcVF-CF3), and N-acetyl-l-leucyl-l
      -phenylalanyl trifluoromethyl ketone (N-AcLF-CF3). The measured DeltadeltaT-H
      values for His57 Hdelta1 in these complexes were between -0.63 and -0.68 ppm.
      These values are consistent with a strong hydrogen bond in each of these
      complexes, but not with a very strong hydrogen bond, which would be expected to
      have a DeltadeltaT-H. value near or greater than zero.

PMID- 11960435
TI  - Phase coherent electronics: a molecular switch based on quantum interference.
AB  - The phenomenon of quantum mechanical interference may be used to control the
      conductivity of ballistic molecular wires. Using a simple model we demonstrate
      plausible effects and discuss its potential uses for constructing coherence-based
      molecular electronics.

PMID- 11960434
TI  - Oxygen transfer from sulfoxides: oxidation of alkylarenes catalyzed by a
      polyoxomolybdate, [PMo12O40]3-.
AB  - The polyoxomolydate of the Keggin structure, PMo12O403-, catalyzes, under
      anaerobic conditions, oxygen transfer from sulfoxides to alkylarenes such as
      xanthene and diphenylmethane to yield xanthen-9-one and benzophenone,
      respectively. With use of 17O and 18O labeled phenylmethylsulfoxide it was shown
      that the sulfoxide is complexed by the polyoxometalate and the oxygen is
      transferred from the sulfoxide to the alkylarene. There is a good correlation
      between the reaction rate and the heterolytic benzylic C-H bond energy indicating
      a hydride transfer reaction from the alkylarene to the polyoxometalate-sulfoxide
      complex. In the case of triphenylmethane the resulting carbocation reacts to
      yield 9-phenylfluorene as the major product. The reaction kinetics supports such
      a reaction pathway.

PMID- 11960436
TI  - Intrinsic deuterium isotope effects on benzylic hydroxylation by tyrosine
      hydroxylase.
AB  - Tyrosine hydroxylase (TyrH) is a mononuclear, non-heme iron monooxygenase that
      catalyzes the pterin-dependent hydroxylation of tyrosine to
      dihydroxyphenylalanine. When 4-methylphenylalanine is used as a substrate for
      TyrH, 4-hydroxymethylphenylalanine is one of the amino acid products. To examine
      the mechanism of benzylic hydroxylation, the products and their isotopic
      compositions were determined with 4-methylphenylalanines containing a mono-, di-,
      or trideuterated methyl group as substrates. Intrinsic primary and secondary
      deuterium isotope effects for benzylic hydroxylation of 9.6 +/- 0.9 and 1.21 +/-
      0.08, respectively, were derived from the data. The magnitudes of these isotope
      effects are consistent with quantum mechanical tunneling of the hydrogen. The
      similarity of the effects to those seen for benzylic hydroxylation by other
      enzymes supports a mechanism where a high valence iron-oxo species, Fe(IV)=O, is
      the hydroxylating intermediate.

PMID- 11960437
TI  - Stereochemistry of the transmetalation of Grignard reagents to copper (I) and
      manganese (II).
AB  - Transmetalation of a chiral secondary Grignard reagent to Cu(I) or Mn(II) occurs
      with partial racemization in a manner that suggests the sequence of two
      transmetalation cycles, one with racemization (caused by ET ?) and the other one
      with (predominant) retention of configuration.

PMID- 11960438
TI  - Dipolar waves as NMR maps of protein structure.
AB  - The anisotropy of nuclear spin interactions results in a unique mapping of
      structure to the resonance frequencies and split tings observed in NMR spectra,
      however, the determination of molecular structure from experimentally measured
      spectral parameters is complicated by angular ambiguities resulting from the
      symmetry properties of dipole-dipole and chemical shift interactions. This issue
      can be addressed through the periodicity inherent in secondary structure
      elements, which can be used as an index of topology. Distinctive wheel-like
      patterns are observed in two-dimensional 1H-15N heteronuclear dipolar/15N
      chemical shift PISEMA (polarization inversion spin-exchange at the magic angle)
      spectra of helical membrane proteins in highly aligned lipid bilayer samples. One
      dimensional dipolar waves are an extension of two-dimensional PISA (polarity
      index slant angle) wheels to map protein structure in NMR spectra of both highly
      and weakly aligned samples. Dipolar waves describe the periodic wavelike
      variations of the magnitudes of the static heteronuclear dipolar couplings as a
      function of residue number in the absence of chemical shift effects. Weakly
      aligned samples of proteins display these same effects, primarily as residual
      dipolar couplings (RDCs), in solution NMR spectra. The corresponding properties
      of the RDCs in solution NMR spectra of weakly aligned helices represent a
      convergence of solid-state and solution NMR approaches to structure
      determination.

PMID- 11960439
TI  - Magnetically-induced solid-state electrochemical detection of DNA hybridization.
AB  - A magnetic triggering of a solid-state electrical transduction of DNA
      hybridization is described. Positioning of an external magnet below the thick
      film electrode attracts the DNA/particle network and enables the solid-state
      electrochemical stripping detection of the silver tracer. TEM imaging indicates
      that the hybridization event results in a three-dimensional aggregate structure
      in which duplex segments link the metal nanoparticles and magnetic spheres, and
      that most of this assembly is covered with the silver precipitate. This leads to
      a direct contact of the metal tag with the surface (in connection to the magnetic
      collection) and enables the solid-state electrochemical transduction (without
      prior dissolution and subsequent electrodeposition of the metal), using oxidative
      dissolution of the silver tracer. No such aggregates (and hence magnetic
      "collection") are observed in the presence of noncomplementary DNA, that is,
      without the linking hybrid. The new method couples high sensitivity of silver
      amplified assays with effective discrimination against excess of closely related
      nucleotide sequences (including single-base imperfections). Such direct
      electrical detection of DNA/metal-particle assemblies can bring new capabilities
      to the detection of DNA hybridization, and could be applied to other bioaffinity
      assays.

PMID- 11960440
TI  - Planar array of 1D gold nanoparticles on ridge-and-valley structured carbon.
AB  - For fabrication of a planar array of 1D chains of gold nanoparticles prepared by
      a chemical process, the faceted (110) planes of sodium chloride crystals were
      used as templates to produce nanoscale ridge-and-valley structured carbon layers
      by a vacuum process. When these carbon layers loaded on copper grids were dipped
      in toluene solution of 3.4 nm gold nanoparticles followed by natural dry, a
      planar array of 1D chains of gold nanoparticles were formed on carbon layers,
      where the nanoparticles were immobilized predominantly in valleys and partly on
      ridges of carbon layers.

PMID- 11960441
TI  - Unusual role of oxygen in electron-transfer processes.
AB  - Molecular oxygen's unique involvement in electron-transfer processes is
      demonstrated on a series of dyads between porphyrin derivatives and fullerene
      C60. It has been shown for the first time that oxygen can serve as an inhibitor
      of back electron transfer by enhancing intersystem crossing of a singlet radical
      ion pair into its triplet state. The effect is observed only when energy of the
      charge-separated state is lower than that of the locally excited triplet states.
      Due to the spin statistics, the reverse intersystem crossing is less efficient,
      allowing use of oxygen and other paramagnetic species for impeding charge
      recombination in various electron-transfer systems.

PMID- 11960442
TI  - Observation of conserved solution-phase secondary structure in gas-phase tryptic
      peptides.
AB  - Results from ion mobility studies of tryptic peptides suggest that, in some
      cases, the gas-phase structures can be related to the solution-phase structure of
      the parent protein. The interpretation of ion mobility measurements is supported
      by results from molecular modeling and H/D exchange experiments on the same
      peptides. This study clearly illustrates the utility of IM-MS for screening
      complex mixtures for peptides having intrinsically stable secondary/tertiary
      structures, and/or posttranslational modification.

PMID- 11960443
TI  - Distinguishing surface versus buried cation sites in aluminosilicate mesoporous
      materials.
AB  - Mesoporous MCM-41 aluminosilicates were prepared through direct synthesis and
      surface grafting resulting in the incorporation of aluminum into the pore walls
      and onto the wall surface, respectively. 7Li and 23Na NMR studies of ion
      exchanged Li and Na-Al-MCM-41 were able to distinguish between cations in the
      surface region and those buried deeper in the pore walls. Thus it was
      demonstrated that most of the cations in the grafted Al-MCM-41 locate in the
      surface region, whereas the cations in the synthesized Al-MCM-41 are distributed
      throughout the pore walls. The NMR spectra of dehydrated Li- and Na-MCM-41
      resemble those of glassy materials, reflecting the amorphous nature of this class
      of mesoporous materials. 7Li NMR studies of dehydrated Li-Al-MCM-41 prepared from
      direct synthesis in the presence of oxygen showed that most of the Li+ cations
      are not accessible to O2, while the Li+ cations in Al-grafted Li-Al-MCM-41 are
      accessible, which also confirms their locations. This study provides valuable
      insights for the understanding of the structure and properties of aluminosilicate
      mesoporous materials.

PMID- 11960444
TI  - Atom-efficient assembly of 1,5-oxygen-bridged medium-sized carbocycles by
      sequential combination of a Ru-catalyzed alkyne-alkene coupling and a Prins-type
      cyclization.
AB  - Ruthenium-catalyzed coupling of readily accessible 1-trimethylsilyl-1-alkyn-3-ols
      to allyl ethyl ether followed by in situ ketalization and Lewis-acid induced
      cyclization affords 1,5-oxygen-bridged eight- and nine-membered carbocycles,
      products which are difficult to construct with previously published strategies.

PMID- 11960445
TI  - Pd(0)-catalyzed reaction of alkynes with trifurylgermane and CO providing
      acylgermanes: the example of hydrometalcarbonylation of alkynes.
AB  - A direct synthesis of acylmetals from alkynes with group 14 metal hydride and CO
      is reported. The Pd(0)-catalyzed reaction of alkynes with tri(2-furyl)germane
      under ambient pressure of CO provides alpha,beta-unsaturated acylgermanes in good
      yields. Conversion of acylgermanes to the corresponding amides is achieved.

PMID- 11960446
TI  - Nickel-catalyzed cross-coupling reaction of grignard reagents with alkyl halides
      and tosylates: remarkable effect of 1,3-butadienes.
AB  - A new method for the cross-coupling reaction of Grignard reagents with alkyl
      chlorides, bromides, and tosylates has been developed by the use of a nickel
      catalyst in the presence of a diene as an additive. This reaction proceeds
      efficiently at 0-25 degrees C in THF using primary and secondary alkyl and aryl
      Grignard reagents. Nickel complexes bearing no phosphine ligands, such as NiCl2,
      Ni(acac)2, and Ni(COD)2, afford the coupling products in good yields, whereas
      NiCl2(PPh3)2 and NiCl2(dppp) were less effective. 1,3-Butadiene shows the highest
      activity as an additive for the present coupling reaction. A plausible reaction
      pathway was proposed.

PMID- 11960447
TI  - Lipase polystyrene giant amphiphiles.
AB  - A new type of giant amphiphilic molecule has been synthesized by covalently
      connecting a lipase enzyme headgroup to a maleimide-functionalized polystyrene
      tail (40 repeat units). The resulting biohybrid forms catalytic micellar rods in
      water.

PMID- 11960448
TI  - Unusually sharp dependence of water exchange rate versus lanthanide ionic radii
      for a series of tetraamide complexes.
AB  - The tetraamide ligand, DOTA-tetra(glycine ethyl ester), forms complexes with the
      lanthanide(III) cations that exist in solution predominantly as the square
      antiprism structure with single, slowly exchanging inner-sphere water molecule.
      Variable-temperature 1H and 17O NMR studies revealed that the bound water
      lifetimes in these complexes were sharply dependent upon the ionic radius of Ln3+
      cation. A novel lanthanide-induced shift technique was used to unmask the bound
      water 17O resonance of SmL3+ and YL3+ complexes from the bulk water resonance.
      The bound water lifetime (tauM298) was approximately 800 mus in the EuL3+ complex
      but became much shorter (several microseconds) for Ln3+ cations with larger and
      smaller ionic radii. This demonstrates that water exchange is exquisitely fine
      tuned in this macrocyclic tetraamide system and that a variety of Ln3+ complexes
      meet with the exchange requirement, Deltaomega*tauM >/= 1, necessary for an
      efficient MT agent.

PMID- 11960449
TI  - Transition-metal nanoparticles in imidazolium ionic liquids: recyclable catalysts
      for biphasic hydrogenation reactions.
AB  - 1-n-Butyl-3-methylimidazolium hexafluorophosphate room-temperature ionic liquid
      is not only suitable as a medium for the preparation and stabilization of iridium
      nanoparticles but also ideal for the generation of recyclable biphasic catalytic
      systems for hydrogenation reactions. Thus, Ir(0) nanoparticles with a mean
      diameter of 2 nm have been prepared by reduction of Ir(I) dissolved in the ionic
      liquid with H2. This catalytic solution can be reused several times for the
      biphasic hydrogenation of olefins under mild reaction conditions.

PMID- 11960450
TI  - Enantioselective synthesis of (-)-terpestacin and (-)-fusaproliferin:
      clarification of optical rotational measurements and absolute configurational
      assignments establishes a homochiral structural series.
AB  - An enantioselective synthesis of the syncytium formation inhibitor (-)
      terpestacin (1, 19 steps, 5.8% yield from the allylation product of (R,R)
      pseudoephedrine propionamide, 3) and the fungal metabolite (-)-fusaproliferin (2,
      21 steps, 5.3% yield from 3) in their natural configurations is described. The
      route employs a series of stereoselective enolate alkylation reactions to
      establish the initial stereogenic center, set the quaternary carbon
      configuration, close the 15-membered ring, and introduce the side-chain residue
      with proper stereocontrol. Careful analysis of our synthetic materials alongside
      natural samples has revealed that several errors were made in the earlier
      measurements of optical rotation or in the absolute stereochemical assignments of
      these natural products. Clarifying all discrepancies, we show here that natural
      terpestacin (1) is levorotatory, not dextrorotatory as originally described, but
      was correctly assigned as the (1S,11S,15R,23S)-enantiomer. Fusaproliferin (2) is
      levorotatory, as reported, but is in fact the (1S,11S,15R,23S)-enantiomer and not
      the antipodal configuration originally assigned.

PMID- 11960451
TI  - Catalytic, enantioselective aldol additions to ketones.
AB  - Catalytic, enantioselective additions of a trichlorosilyl ketene acetal to
      ketones have been demonstrated. The trichlorosilyl enolate of methyl acetate
      undergoes a rapid and high-yielding aldol addition to a wide range of ketones
      (aromatic, olefinic, acetylenic, aliphatic) in the presence of a catalytic amount
      of pyridine N-oxide. Moreover, in the presence of a catalytic amount (10 mol %)
      of a chiral bispyridine bis N-oxide (possessing both axial and central chiral
      elements) the aldol addition takes place again in excellent yield and with good
      stereoselectivity. The enantioselectivities of the additions are highly variable
      (7-86% ee) and are strongly dependent on the structure of the ketone acceptor.
      Aromatic methyl ketones gave the highest selectivity, whereas olefinic ketones
      were the least selective.

PMID- 11960452
TI  - On the effect of covalently appended quinolones on termini of DNA duplexes.
AB  - Quinolones are gyrase inhibitors that are widely used as antibiotics in the
      clinic. When covalently attached to oligonucleotides as 5'-acylamido
      substituents, quinolones were found to stabilize duplexes of oligonucleotides
      against thermal denaturation. For short duplexes, such as qu-T*GCGCA, where qu is
      a quinolone residue and T is a 5'-amino-5'-deoxythymidine residue, an increase in
      the UV melting point of up to 27.8 degrees C was measured. The stabilizing effect
      was demonstrated for all quinolones tested, namely nalidixic acid, oxolinic acid,
      pipemidic acid, cinoxacin, norfloxacin, and ofloxacin. The three-dimensional
      structure of (oa-T*GCGCA)2, where oa is an oxolinic acid residue, was solved by
      two-dimensional NMR spectroscopy and restrained molecular dynamics. In this
      complex, the oxolinic acid residues disrupt the terminal T1:A6 base pairs and
      stack on the G2:C5 base pairs. The displaced adenosine residues bind in the minor
      groove of the core duplex, while the thymidine residues pack against the oxolinic
      acid residues. The "molecular cap" thus formed fits tightly on the G:C base
      pairs, resulting in increased base-pairing fidelity, as demonstrated in UV
      melting experiments with the sequence oa-T*GGTTGAC and target strands containing
      a mismatched nucleobase. The structure of the "molecular cap" with its disrupted
      terminal base pair may also be helpful for modeling how quinolones block re
      ligation of DNA strands in the active site of gyrases.

PMID- 11960453
TI  - Sol-gel encapsulated horseradish peroxidase: a catalytic material for
      peroxidation.
AB  - This study addresses the viability of sol-gel encapsulated HRP (HRP:sol-gel) as a
      recyclable solid-state catalytic material. Ferric, ferric-CN, ferrous, and
      ferrous-CO forms of HRP:sol-gel were investigated by resonance Raman and UV
      visible methods. Electronic and vibrational spectroscopic changes associated with
      changes in spin state, oxidation state, and ligation of the heme in HRP:sol-gel
      were shown to correlate with those of HRP in solution, showing that the heme
      remains a viable ligand-binding complex. Furthermore, the high-valent HRP:sol-gel
      intermediates, compound I and compound II, were generated and identified by time
      resolved UV-visible spectroscopy. Catalytic activity of the HRP:sol-gel material
      was demonstrated by enzymatic assays by using I(-), guaiacol, and ABTS as
      substrates. Encapsulated HRP was shown to be homogeneously distributed throughout
      the sol-gel host. Differences in turnover rates between guaiacol and I(-)
      implicate mass transport of substrate through the silicate matrix as a defining
      parameter in the peroxidase activity of HRP:sol-gel. HRP:sol-gel was reused as a
      peroxidation catalyst for multiple reaction cycles without loss of activity,
      indicating that such materials show promise as reusable catalytic materials.

PMID- 11960454
TI  - Selective sterol-phospholipid associations in fluid bilayers.
AB  - The nearest-neighbor preferences of three exchangeable lipid monomers (two
      phospholipids that differ in length, A and B, and a derivative of cholesterol, C)
      have been quantified in the fluid bilayer state by use of the nearest-neighbor
      recognition method (Davidson, S. K. M.; Regen, S. L. Chem. Rev. 1997, 97, 1269).
      Thus, an analysis of the equilibrium dimer distributions has shown that (i) the
      sterol favors both phospholipids as nearest neighbors relative to other sterol
      molecules, (ii) that this recognition is selective (i.e., the sterol favors the
      longer phospholipid as a nearest neighbor over the shorter one, especially when
      the sterol concentrations in the bilayer is high (e.g., 40 mol %), and (iii) the
      phospholipids, themselves, are unable to recognize each other. Taken together,
      these findings indicate that the probable mechanism by which cholesterol induces
      homoassociation of A and B in analogous bilayers is one in which the sterol
      "pulls" two or more of the longer phospholipid monomers (B) out of a "sea" of
      randomly mixed A and B. These findings also lend support for the notion of
      cholesterol-phospholipid complexation in fluid bilayers. The biological
      implications of these findings are briefly discussed.

PMID- 11960455
TI  - A convergent three-component total synthesis of the powerful immunosuppressant (
      )-sanglifehrin a.
AB  - The potent immunosuppressive agent (-)-sanglifehrin A (5), initially discovered
      in a soil sample from Malawi, has been synthesized in a highly convergent and
      stereocontrolled manner. The enantioselective approach relies on initial
      construction of the iodovinyl carboxylic acid 14, which is coupled to tripeptide
      59 in advance of a key macrolactonization step that generates 61a. An alternative
      protocol that involves the linkage of 14 to 46 for possible construction of the
      large ring failed due to an inability to bring about a corresponding
      macrolactamization maneuver. An efficient means for elaborating the C26-N42
      spirolactam western sector of 5 is also detailed. This requisite fragment was
      assembled through the proper adaptation of consecutive aldol tactics for
      construction of the nine stereogenic centers, six of which are contiguous. The
      first aldol process consisted of the tin triflate-mediated reaction of the
      aldehyde derived from 72 with enantiopure ketone 73 to generate the syn C36-C37
      relationship resident in 75. Once the conversion of 75 to 78 had been completed,
      the attachment to ketone 66 was effected with (+)-DIPCl, thereby setting the C33
      C34 relationship as anti. Once functional group modifications had given rise to
      62, spirolactamization was achieved to deliver predominantly 94, thereby setting
      the stage for the acquisition of vinyl stannane 13 and its subsequent palladium
      catalyzed Stille coupling to 61b. Controlled acidic hydrolysis completed the
      synthesis of 5. Other important features of the present route are addressed where
      relevant.

PMID- 11960456
TI  - Cyclopropylcarbinyl-type ring openings. Reconciling the chemistry of neutral
      radicals and radical anions.
AB  - Cyclopropylcarbinyl --> homoallyl and related rearrangements of radical ions (a)
      are frequently used as mechanistic "probes" to detect the occurrence of single
      electron transfer in chemical and biochemical processes, (b) provide the basis
      for mechanism-based drug design, and (c) are important tools in organic
      synthesis. Unfortunately, these rearrangements are poorly understood, especially
      with respect to the effect of substrate structure on reactivity. Frequently,
      researchers assume that the same factors which govern the reactivity of neutral
      free radicals also pertain to radical ions. The results reported herein
      demonstrate that in some cases structure-reactivity trends in radical ion
      rearrangements are very different from neutral radicals. For radical ions,
      delocalizations of both charge and spin are important factors governing their
      reactivity.

PMID- 11960457
TI  - Asymmetric synthesis of A-240610.0 via a new atropselective approach for axially
      chiral biaryls with chirality transfer.
AB  - A new approach for atropselective preparation of axially chiral biaryl was
      developed. This process proceeded through a chirality transfer from a stereogenic
      center of a secondary alcohol to the stereogenic axis via regioselective
      intramolecular silyl group migration. This methodology allowed for the
      preparation of a single atropisomer 2 in good yield (85%) with high
      diastereoselectivity (99:1), which subsequently led to the successful development
      of an efficient asymmetric synthesis of A-240610.0, 1.

PMID- 11960458
TI  - Self-complementarity of oligo-2-aminopyridines: a new class of hydrogen-bonded
      ladders.
AB  - A new class of hydrogen-bonded ladders based on hydrogen-bonded dimerization of
      oligo-alpha-aminopryidines has been demonstrated. Jorgensen's model can be
      successfully applied to this hydrogen-bonding system in nonpolar solvents. The
      results show the competitive enthalpy/entropy compensation relationship upon
      dimerization. Although increasing the number of hydrogen-bonding interactions
      would enhance the hydrogen-bonding stabilization enthalpy, this stabilization
      enthalpy per unit would be partially sacrificed to compensate for the entropy
      loss due to dimerization. These results clearly support the importance of
      preorganization in designing hydrogen-bonding guest-host molecules.

PMID- 11960459
TI  - Extreme electronic modulation of the cofacial porphyrin structural motif.
AB  - The synthesis, electrochemistry, and optical spectroscopy of an extensive series
      of cofacial bis[(porphinato)zinc(II)] compounds are reported. These species were
      synthesized using sequential palladium-catalyzed cross-coupling and cobalt
      mediated [2+2+2] cycloaddition reactions. This modular methodology enables facile
      control of the nature of macrocycle-to-macrocycle connectivity and allows
      unprecedented modulation of the redox properties of face-to-face porphyrin
      species. We report the synthesis of 5,6-bis[(5',5''-10',20'-bis[4-(3-methoxy-3
      methylbutoxy)phenyl]porphinato)zinc(II)]indane (1), 5,6-bis[(2'-5',10',15',20'
      tetraphenylporphinato)zinc(II)]indane (2), 5-([2'-5',10',15',20'
      tetraphenylporphinato]zinc(II))-6-[(5"-10'',20''-bis[4-(3-methoxy-3
      methylbutoxy)phenyl]porphinato)zinc(II)]indane (3), 5-([2'-5',10',15',20'
      tetrakis(trifluoromethyl)porphinato]zinc(II))-6-[(5' '-10' ',20' '-bis[4-(3
      methoxy-3-methylbutoxy)phenyl]porphinato)zinc(II)]indane (4), 5-(2'
      5',10',15',20'-[tetrakis(trifluoromethyl)porphinato]zinc(II))-6-[(2''
      5'',10'',15'',20''-tetraphenylporphinato)zinc(II)]indane (5), 5,6-bis([2'-5',15'
      diphenyl-10',20'-(trifluoromethyl)porphinato]zinc(II))indane (6), and 5,6-bis([2'
      5',10',15',20'-tetrakis(trifluoromethyl)porphinato]zinc(II))indane (7); 4-7
      define the first examples of cofacial bis[(porphinato)metal] compounds in which
      sigma-electron-withdrawing perfluoroalkyl groups serve as macrocycle
      substituents, while 2, 6, and 7 constitute the first such structures that possess
      a beta-to-beta linkage topology. Cyclic voltammetric studies show that the
      electrochemically determined HOMO and LUMO energy levels of these cofacial
      bis(porphinato) complexes can be lowered by 780 and 945 mV, respectively,
      relative to the archetypal members of this class of compounds; importantly, these
      orbital energy levels can be modulated over well-defined increments throughout
      these wide potentiometric domains. Analyses of these cofacial
      bis[(porphinato)metal] potentiometric data, in terms of the absolute and relative
      frontier orbital energies of their constituent [porphinato]zinc(II) building
      blocks, as well as the nature of macrocycle-to-macrocycle connectivity, provide
      predictive electronic structural models that rationalize the redox behavior of
      these species.

PMID- 11960460
TI  - Functional analogue reaction systems of the DMSO reductase isoenzyme family:
      probable mechanism of S-oxide reduction in oxo transfer reactions mediated by
      bis(dithiolene)-tungsten(IV,VI) complexes.
AB  - The recent development of structural and functional analogues of the DMSO
      reductase family of isoenzymes allows mechanistic examination of the minimal
      oxygen atom transfer paradigm M(IV) + QO M(VI) O + Q with the biological metals M
      = Mo and W. Systematic variation of the electronic environment at the WIV center
      of desoxo bis(dithiolene) complexes is enabled by introduction of para
      substituted phenyl groups in the equatorial (eq) dithiolene ligand and the axial
      (ax) phenolate ligand. The compounds [W(CO)2(S2C2(C6H4-p-X)2)2] (54-60%) have
      been prepared by ligand transfer from [Ni(S2C2(C6H4-p-X)2)2] to [W(CO)3(MeCN)3].
      A series of 25 complexes [W(IV)(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- ([X4,X'], X =
      Br, F, H, Me, OMe; X' = CN, Br, H, Me, NH2; 41-53%) has been obtained by ligand
      substitution of five dicarbonyl complexes with five phenolate ligands. Linear
      free energy relationships between E1/2 and Hammett constant p for the electron
      transfer series [Ni(S2C2(C6H4-p-X)2)2]0,1-,2- and [W(CO)2(S2C2(C6H4-p-X)2)2]0,1
      ,2- demonstrate a substituent influence on electron density distribution at the
      metal center. The reactions [WIV(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- + (CH2)4SO
      [W(VI)O(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- + (CH2)4S with constant substrate are
      second order with large negative activation entropies indicative of an
      associative transition state. Rate constants at 298 K adhere to the Hammett
      equations log(k([X4,X']/k[X4,H]) = rho(ax)sigma(p) and log(k[X4,X']/k([H4,X']) =
      4rho(eq)sigma(p). Electron-withdrawing groups (EWG) and electron-donating groups
      (EDG) have opposite effects on the rate such that k(EWG) > k(EDG). The effects of
      X' on reactivity are found to be approximately 5 times greater than that of X
      (rho(ax) = 2.1, rho(eq) = 0.44) in the Hammett equation. Using these and other
      findings, a stepwise oxo transfer reaction pathway is proposed in which an early
      transition state, of primary W(IV)-O(substrate) bond-making character, is rate
      limiting. This is followed by a six-coordinate substrate complex and a second
      transition state proposed to involve atom and electron transfer leading to the
      development of the W(VI)=O group. This work is the most detailed mechanistic
      investigation of oxo transfer mediated by a biological metal.

PMID- 11960461
TI  - A new strategy for the enantioselective synthesis of carba-prostacyclin analogues
      based on organocopper conjugate addition to a bicyclic azoene and its application
      to the synthesis of 13,14-dinor-inter-p-phenylene carbacyclin.
AB  - An enantioselective synthesis of E/Z-13,14-dinor-inter-p-phenylene carbacyclin
      (E/Z-2d) by a new strategy has been realized that holds the prospect of serving
      as a general route for carba-prostacyclin analogues. The key intermediate in this
      synthesis is the bicyclic azoene Ts-9, and the key step is the regio- and
      stereoselective conjugate addition of the chiral arylcopper compound Cu-8d/P-n
      Bu3 to the azoene with formation of hydrazone 7d. Enantioselective synthesis of
      azoene Ts-9 of 95% ee from ketone 4 was accomplished in four and five steps,
      respectively. Thus, enantioselective deprotonation of bicyclic ketone 4 with
      chiral base Li-10 and trapping of lithium enolate 11 with ClSiMe3 gave enol ether
      12, which was chlorinated with N-chlorosuccinimide (NCS) to afford chloro ketone
      13. Alternatively, chloro ketone 13 was also prepared upon chlorination of 11
      with NCS. Chloro ketone 13 was converted to chloro hydrazone 14, which upon
      treatment with a mild base furnished azoene Ts-9. Arylcopper compound 8d of 98%
      ee was obtained in two steps from alcohol 16, which was prepared by
      enantioselective reduction of ketone 17 with (-)-diisopinocampheylchloroborane.
      Carbacyclin derivative E/Z-2d was found to be essentially inactive as an
      inhibitor of ADP induced human platelet aggregation, having an IC50 of >10
      micromol/L.

PMID- 11960462
TI  - Regioselective synthesis and properties of novel [60]fullerene bisadducts
      containing a dibenzocrown ether moiety.
AB  - The reactions of [60]fullerene with bis-o-quinodimethane precursors 3, 4, and 5
      containing a dibenzo-18-crown-6, 24-crown-8 and 30-crown-10 moiety, respectively,
      were investigated. Both 3 and 4 provided trans-4 bisadducts 6a and 7a,
      respectively, as major product, though the selectivity in the latter was lower
      than that in the former. As minor product, 6b (cis-2) was produced from 3, while
      7c (e) as well as 7b (cis-2) were produced from 4. Precursor 5 exclusively
      afforded e bisadduct 8 without any other regioisomers. These bisadducts showed
      different ionophoric properties from one another; for instance, 6a and 7b
      exhibited a high complexing ability toward the K+ ion, while 6b hardly showed
      complexation with any alkali metal ions. The selectivity coefficients
      (K(Na,K)(pot)) of 6a and 7b toward K+ over Na+ ion, determined with an ion
      selective electrode, were much higher than that of dibenzo-18-crown-6.

PMID- 11960463
TI  - Palladium-arene interactions in catalytic intermediates: an experimental and
      theoretical investigation of the soft rearrangement between eta1 and eta2
      coordination modes.
AB  - A series of dichloro-bridged arylbicycloheptylpalladium complexes have been
      synthesized and characterized by means of NMR spectroscopy. The compound
      [(C16H19)PdCl]2*CH2Cl2 with ortho and para methyl substituents at the arene has
      been characterized by means of X-ray diffraction techniques. The C(ipso) atom of
      the arene lies almost at the fourth planar coordination site of the metal [Pd
      C(ipso) = 2.22(1) A (average)], and due to the arene's tilting, the substituted
      C(ortho) atom is relatively close to the metal atom [2.54(1) A (average)]. The
      coordinated C(ipso)-C(ortho) linkage, in a seemingly dihapto coordination, is
      anti with respect to the CH2 bridge of the bicycloheptyl unit. Variable
      temperature NMR experiments for the para-substituted dimer 9 reveal restricted
      rotation of the two aryl groups about the corresponding C-C(ipso) bonds (DeltaE <
      or =17 kcal x mol(-1)). DFT-B3LYP calculations have been carried out on the known
      and similar monomer (phenylbicycloheptenyl)Pd(PPh3)I (4) and its related
      substituted derivatives. The essential results are as follows: (i) The potential
      energy surface for twisting the phenyl ring away from the symmetric eta(1)
      coordination in 4 is very flat (DeltaE < or = 1 kcal x mol(-1)) whereas an Atoms
      in Molecules analysis excludes the existence of an actual Pd-C(ortho) bond in the
      seemingly eta2-type conformer. (ii) Complete rotation of the unsubstituted phenyl
      ring is not facile but feasible. A significant strain affects the transition
      state structure featuring a Pd-HC(aryl) agostic-type bond. The calculated
      destabilization of 10.3 kcal x mol(-1), with respect to the ground state, can be
      compared to the experimental barrier of the dimer 9. (iii) Various methyl
      substituted derivatives of 4 have been optimized, and their structural and
      energetic trends are discussed. An almost ideal eta1 coordination is shown by the
      anti conformer of the C(ortho)-substituted complex due steric effects. For all of
      the other cases, a slipped eta2 coordination may be described. As a general
      conclusion, the unsaturated metal center receives pi electron density of the
      arene mainly through its C(ipso) atom. The effect may be slightly improved if the
      C(ortho) atom also gets closer to the metal, but in no case, does the slipped
      eta2 coordination seem to be crucial for the stability of the system.

PMID- 11960464
TI  - Long-range electron transfer in porphyrin-containing [2]-rotaxanes: tuning the
      rate by metal cation coordination.
AB  - A series of [2]-rotaxanes has been synthesized in which two Zn(II)-porphyrins
      (ZnP) electron donors were attached as stoppers on the rod. A macrocycle attached
      to a Au(III)-porphyrin (AuP+) acceptor was threaded on the rod. By selective
      excitation of either porphyrin, we could induce an electron transfer from the ZnP
      to the AuP+ unit that generated the same ZnP*+-AuP* charge-transfer state
      irrespective of which porphyrin was excited. Although the reactants were linked
      only by mechanical or coordination bonds, electron-transfer rate constants up to
      1.2x10(10) x s(-1) were obtained over a 15-17 A edge-to-edge distance between the
      porphyrins. The resulting charge-transfer state had a relatively long lifetime of
      10-40 ns and was formed in high yield (>80%) in most cases. By a simple variation
      of the link between the reactants, viz. a coordination of the phenanthroline
      units on the rotaxane rod and ring by either Ag+ or Cu+, we could enhance the
      electron-transfer rate from the ZnP to the excited 3AuP+. We interpret our data
      in terms of an enhanced superexchange mechanism with Ag+ and a change to a
      stepwise hopping mechanism with Cu+, involving the oxidized Cu(phen)22+ unit as a
      real intermediate. When the ZnP unit was excited instead, electron transfer from
      the excited 1ZnP to AuP+ was not affected, or even slowed, by Ag+ or Cu+. We
      discuss this asymmetry in terms of the different orbitals involved in mediating
      the reaction in an electron- and a hole-transfer mechanism. Our results show the
      possibility to tune the rates of electron transfer between noncovalently linked
      reactants by a convenient modification of the link. The different effect of Ag+
      and Cu+ on the rate with ZnP and AuP+ excitation shows an additional possibility
      to control the electron-transfer reactions by selective excitation. We also found
      that coordination of the Cu+ introduced an energy-transfer reaction from 1ZnP to
      Cu(phen)2+ (k = 5.1x10(9) x s(-1)) that proceeded in competition with electron
      transfer to AuP+ and was followed by a quantitative energy transfer to give the
      3ZnP state (k = 1.5x10(9) x s(-1)).

PMID- 11960465
TI  - Monolayers as models for supported catalysts: zirconium phosphonate films
      containing manganese(III) porphyrins.
AB  - Organized monolayer films of a manganese tetraphenylporphyrin have been prepared
      and used as supported oxidation catalysts. Manganese 5,10,15,20
      tetrakis(tetrafluorophenyl-4'-octadecyloxyphosphonic acid) porphyrin (1) has been
      immobilized as a monolayer film by a combination of Langmuir-Blodgett (LB) and
      self-assembled monolayer techniques that use zirconium phosphonate linkages to
      bind the molecule to the surface. Analysis by FTIR, XPS, UV-vis and polarized
      optical spectroscopy show that the films consist of noninteracting molecules
      effectively anchored and oriented nearly parallel to the surface. The monolayer
      films are stable to the solvent and temperature conditions needed to explore
      organic oxidations. The activity of films of 1 toward the epoxidation of
      cyclooctene using iodosylbenzene as the oxidant was compared to that of Manganese
      5,10,15,20-tetrakis(pentafluorophenyl) porphyrin (2) and 1 under equivalent
      homogeneous conditions. The immobilized porphyrin 1 shows an enhanced activity
      relative to either homogeneous reaction. The main difference between 1 and 2 is
      the four alkyl phosphonate arms in 1 designed to incorporate the porphyrin within
      the films. The increased activity of immobilized 1 is a combination of the
      porphyrin structure, which prohibits the formation of mu-oxo dimers even in
      solution, and a change in conformation when anchored to the surface. The study
      demonstrates that careful monolayer studies can provide useful models for the
      design and study of supported molecular catalyst systems.

PMID- 11960466
TI  - The s-p bonded representatives of the prominent BaAl4 structure type: a case
      study on structural stability of polar intermetallic network structures.
AB  - This work presents a detailed, combined experimental and theoretical study on the
      structural stability of s-p bonded compounds with the BaAl4 structure type (space
      group I4/mmm, Z = 2) as part of a broad program to investigate the complex
      questions of structure formation and atomic arrangements in polar intermetallics.
      From ab initio calculations employing pseudopotentials and a plane wave basis
      set, we extracted optimized structural parameters, binding energies, and the
      electronic structure of the systems AeX(III)4, AeX(II)2X(IV)2, AeX(II)2X(III)2
      (Ae = Ca, Sr, Ba; X(II) = Mg, Zn; X(III) = Al, Ga; X(IV) = Si, Ge). For all
      systems we found a pronounced pseudo-gap in the density of states separating
      network X42- bonding from antibonding electronic states that coincides with the
      Fermi level for an electron count of 14 electrons per formula unit, the optimum
      value for stable BaAl4-type polar intermetallics. However, the synthesis and
      structural characterization (from X-ray single crystal and powder diffraction
      data) of the new compounds AeZn2-Al2+, AeZn2-deltaGa2+delta (Ae = Ca, Sr, Ba;
      delta = 0-0.2) and AeMg0.9Al3.1, AeMg1.7Ga2.3 (Ae = Sr, Ba) manifested that
      electron deficiency is rather frequent for BaAl4-type polar intermetallics. The
      site preference for different "X" elements in the ternary systems was quantified
      by calculating "coloring energies", which, for some systems, was strongly
      dependent on the size of the electropositive Ae component. The Ae2+ cations
      decisively influence the nearest neighbor distances in the encapsulating
      polyanionic networks X4(2-) and the structures of these networks are surprisingly
      flexible to the size of the Ae component without changing the overall bonding
      picture. A monoclinically distorted variant of the BaAl4 structure occurs when
      the cations become too small for matching the size of encapsulating X4(2-) cages.
      An even larger size mismatch leads to the formation of the EuIn4 structure type.

PMID- 11960467
TI  - Mechanistic comparison of cyclic ester polymerizations by novel iron(III)
      alkoxide complexes: single vs multiple site catalysis.
AB  - The complexes Fe2(OCHPh2)6 and L2FeOR (R = Et or CHPh2, L = N,N'
      bis(trimethylsilyl)benzamidinate) were structurally characterized, and
      comparative studies of the behavior of those compounds comprising the same
      alkoxide (Ph2HCO-) in polymerizations of -caprolactone (CL) and D,L-lactide (LA)
      were performed. Both Fe2(OCHPh2)6 and L2FeOCHPh2 are effective polymerization
      catalysts, as reflected by molecular weight control, polydispersities, and end
      group analysis, but the diiron complex generally exhibits greater polymerization
      control, particularly for CL. Kinetic investigations of the polymerization of CL
      revealed the same first-order dependence on [CL] for both catalysts, but
      different orders in [catalyst] that signified a distinct contrast in mechanism.
      Analysis that invoked the presence of a termination-causing impurity at low
      concentration yielded a first-order dependence on [Fe2(OCHPh2)6], but the order
      in [L2FeOCHPh2] was found to be one-half. This fractional dependence was
      interpreted by using a model of active chain aggregation. Comparison of the
      derived propagation rate constants (k(prop)) revealed a approximately 50-fold
      greater value for the diiron complex compared to the single site mononuclear
      compound. Implications of these findings for understanding cyclic ester
      polymerization mechanisms and catalyst design are discussed.

PMID- 11960468
TI  - Artifacts in the electron paramagnetic resonance spectra of C60 fullerene ions:
      inevitable C120O impurity.
AB  - Aspects of the electron paramagnetic resonance (EPR) spectra of C60n- fulleride
      ions (n = 2, 3) and the EPR signal observed in solid C60 are reinterpreted.
      Insufficient levels of reduction and the unrecognized presence of C120O, a
      ubiquitous and unavoidable impurity in air-exposed C60, have compromised most
      previously reported spectra of fullerides. Central narrow line width signals
      ("spikes") are ascribed to C120On- (n = odd). Signals arising from axial triplets
      (g approximately 2.0015, D = 26-29 G) in the spectrum of C602- are ascribed to
      C120On- (n = 2 or 4). Their D values are more realistic for C120O than C60. Less
      distinct signals from "powder" triplets (D approximately 11 G) are ascribed to
      aggregates of C120On- (n = odd) arising from freezing nonglassing solvents. In
      highly purified samples of C60, we find no evidence for a broad approximately 30
      G signal previously assigned to a thermally accessible triplet of C60(2-). The
      C60(2-) ion is EPR-silent. Signals previously ascribed to a quartet state of the
      C60(3-) ion are ascribed to C120O4-. Uncomplicated, authentic spectra of C60- and
      C60(3-) become available when fully reduced samples are prepared under strictly
      anaerobic conditions from freshly HPLC-purified C60. Solid off-the-shelf C60 has
      an EPR signal (g approximately 2.0025, DeltaH(pp) approximately 1.5 G) that is
      commonly ascribed to the radical cation C60*+. This signal can be reproduced by
      exposing highly purified, EPR-silent C60 to oxygen in the dark. Doping C60 with
      an authentic C60*+ salt gives a signal with much greater line width (DeltaH(pp) =
      6-8 G). It is suggested that the EPR signal in air-exposed samples of C60 arises
      from a peroxide-bridged diradical, *C60-O-O-C60* or its decomposition products
      rather than from C60*+. Solid-state C60 is more sensitive to oxygen than
      previously appreciated such that contamination with C120O is almost impossible to
      avoid.

PMID- 11960469
TI  - Control of stability through overlap matching: closo-carborynes and closo
      silaborynes.
AB  - The matching of ring and cap orbitals for overlap is used to arrive at the best
      carborynes among the many possibilities. Accordingly, 1,2-carboranes, 1,2
      silaboranes (C2BnHn+2, and Si2BnHn+2, n = 4, 5, 8, and 10), and their dehydrogeno
      derivatives were studied with use of the Density Functional Theory (B3LYP/6
      311+G*). The dehydrogenation of 2,3-C2B5H7 (6a) to 2,3-C2B5H5 (13a) is estimated
      to be even less endothermic than those of benzene and 1,2- C2B10H12 (1a) to
      benzyne and 1,2-C2B10H10 (8a) by more than 21 kcal/mol. This is due to the extra
      stabilization gained through better overlap of the C2B3H3 ring with the 2 BH
      caps. The relatively larger size of the Si atom leads to overlap requirements in
      silaboranes that are different from those in carboranes. The lower Si-Si single
      bond energy and the preference of Si for lower coordination result in unusual
      structures in dehydrogenosilaboranes. One of the Si atoms moves away from the
      surface in Si2B10H10 (15), Si2B8H8 (16, 17, and 18), and 1,2-Si2B5H5 (19). One Si
      atom forms a bridge to a trigonal surface in 2,3-Si2B5H5 (20) and 1,2-Si2B4H4
      (21). Estimates of three-dimensional aromaticity with NICS calculations show that
      the exohedral double bond does not influence three-dimensional aromaticity.

PMID- 11960470
TI  - Theoretical studies to understand surface chemistry on carbon anodes for lithium
      ion batteries: how does vinylene carbonate play its role as an electrolyte
      additive?
AB  - To elucidate the role of vinylene carbonate (VC) as a solvent additive in organic
      polar solutions for lithium-ion batteries, reductive decompositions for vinylene
      carbonate (VC) and ethylene carbonate (EC) molecules have been comprehensively
      investigated both in the gas phase and in solution by means of density functional
      theory calculations. The salt and solvent effects are incorporated with the
      clusters (EC)nLi+(VC) (n = 0-3), and further corrections that account for bulk
      solvent effects are added using the polarized continuum model (PCM). The electron
      affinities of (EC)nLi+(VC) (n = 0-3) monotonically decrease when the number of EC
      molecules increases; a sharp decrease of about 20.0 kcal/mol is found from n = 0
      to 1 and a more gentle variation for n > 1. For (EC)nLi+(VC) (n = 1-3), the
      reduction of VC brings about more stable ion-pair intermediates than those due to
      reduction of the EC molecule by 3.1, 6.1, and 5.3 kcal/mol, respectively. This
      finding qualitatively agrees with the experimental fact that the reduction
      potential of VC in the presence of Li salt is more negative than that of EC. The
      calculated reduction potentials corresponding to radical anion formation are
      close to the experimental potentials determined with cyclic voltammetry on a gold
      electrode surface (-2.67, -3.19 eV on the physical scale for VC and EC
      respectively vs experimental values -2.96 and -2.94 eV). Regarding the
      decomposition mechanisms, the VC and EC moieties undergo homolytic ring opening
      from their respective reduction intermediates, and the energy barrier of VC is
      about one time higher than that of EC (e.g., 20.1 vs 8.8 kcal/mol for
      (EC)2Li+(VC)); both are weakly affected by the explicit solvent molecules and by
      a bulk solvent represented by a continuum model. Alternatively, starting from the
      VC-reduction intermediate, the ring opening of the EC moiety via an
      intramolecular electron-transfer transition state has also been located; its
      barrier lies between those of EC and VC (e.g., 17.2 kcal/mol for (EC)2Li+(VC)).
      On the basis of these results, we suggest the following explanation about the
      role that VC may play as additive in EC-based lithium-ion battery electrolytes;
      VC is initially reduced to a more stable intermediate than that from EC
      reduction. One possibility then is that the reduced VC decomposes to form a
      radical anion via a barrier of about 20 kcal/mol, which undergoes a series of
      reactions to give rise to more active film-forming products than those resulting
      from EC reduction, such as lithium divinylene dicarbonate, Li-C carbides, lithium
      vinylene dicarbonate, R-O-Li compound, and even oligomers with repeated vinylene
      and carbonate-vinylene units. Another possibility starting from the VC-reduction
      intermediate is that the ring opening occurs on the unreduced EC moiety instead
      of being on the reduced VC, via an intramolecular electron transfer transition
      state, the energy barrier of which is lower than that of the former, in which VC
      just helps the intermediate formation and is not consumed. The factors that
      determine the additive functioning mechanism are briefly discussed, and
      consequently a general rule for the selection of electrolyte additive is
      proposed.

PMID- 11960471
TI  - The energy landscape of unsolvated peptides: helix formation and cold
      denaturation in Ac-A4G7A4 + H+.
AB  - Ion mobility measurements and molecular dynamics simulations were performed for
      unsolvated A4G7A4 + H+ and Ac-A4G7A4 + H+ (Ac = acetyl, A = alanine, G = glycine)
      peptides. As expected, A4G7A4 + H+ adopts a globular conformation (a compact,
      random-looking, three-dimensional structure) over the entire temperature range
      examined (100-410 K). Ac-A4G7A4 + H+ on the other hand is designed to have a flat
      energy landscape with a marginally stable helical state. This peptide shows at
      least four different conformations at low temperatures (<230 K). The two
      conformations with the largest cross sections are attributed to - and partial 
      helices, while the one with the smallest cross section is globular. The other
      main conformation may be partially helical. Ac-A4G7A4 + H+ becomes predominantly
      globular at intermediate temperatures and then becomes more helical as the
      temperature is raised further. This unexpected behavior may be due to the helix
      having a higher vibrational entropy than the globular state, as predicted by some
      recent calculations (Ma, B.; Tsai, C.-J.; Nussinov, R. Biophys. J. 2000, 79, 2739
      2753).

PMID- 11960472
TI  - A microfluidic device with a linear temperature gradient for parallel and
      combinatorial measurements.
AB  - Methods for obtaining combinatorial and array-based data as a function of
      temperature are needed in the chemical and biological sciences. It is presently
      quite difficult to employ temperature as a variable using standard wellplate
      formats simply because it is very inconvenient to keep each well at a distinct
      temperature. In microfluidics, however, the situation is very different due to
      the short length scales involved. In this article, it is shown how a simple
      linear temperature gradient can be generated across dozens of parallel
      microfluidic channels simultaneously. This result is exploited to rapidly obtain
      activation energies from catalytic reactions, melting point transitions from
      lipid membranes, and fluorescence quantum yield curves from semiconductor
      nanocrystal probes as a function of temperature. The methods developed here could
      quite easily be extended to protein crystallization, phase diagram measurements,
      chemical reaction optimization, or multivariable experiments.

PMID- 11960473
TI  - Photoinduced electron-transfer processes along molecular wires based on
      phenylenevinylene oligomers: a quantum-chemical insight.
AB  - Quantum-chemical techniques are applied to model the mechanisms of photoinduced
      charge transfer from a pi-electron donating group (tetracene, D) to a pi-electron
      acceptor moiety (pyromellitimide, A) separated by a bridge of increasing size (p
      phenylenevinylene oligomers, B). Correlated Hartree-Fock semiempirical approaches
      are exploited to calculate the four main parameters controlling the transfer rate
      (k(RP)) in the framework of Marcus-Jortner-Levich's formalism: (i) the electronic
      coupling between the initial and final states; (ii) and (iii) the internal and
      external reorganization energy terms; and (iv) the variation of the free Gibbs
      energy. The charge transfer is shown to proceed in these compounds through two
      competing mechanisms, coherent (superexchange) versus incoherent (bridge
      mediated) pathways. While superexchange is the dominant mechanism for short
      bridges, incoherent transfer through hopping along the phenylene vinylene segment
      takes over in longer chains (for ca. three phenylenevinylene repeat units). The
      influence of the chemical structure of the pi-conjugated phenylenevinylene bridge
      on the electronic properties and the rate of charge transfer is also
      investigated.

PMID- 11960474
TI  - Formation and characterization of the gallium and indium subhydride molecules
      Ga2H2 and In2H2: a matrix isolation study.
AB  - Ga2 reacts spontaneously with H2 in solid Ar matrixes at 12 K to form the cyclic
      molecule Ga(mu-H)2Ga. In2 does not react with H2 under similar conditions, but
      irradiation at wavelengths near 365 nm induces the formation of the corresponding
      indium hydride, In(mu-H)2In. The molecules have been identified and characterized
      by the IR spectra displayed by matrixes containing the metal and H2, D2, HD, or
      H2 + D2; they each have planar, dihydrido-bridged structures with D2h symmetry,
      as endorsed by comparison of the measured spectra (i) with the properties
      forecast by quantum chemical calculations and (ii) with the spectra of known
      gallium and indium hydrides. Both are photolabile under visible light (lambda >
      450 nm): green light (lambda = ca. 546 nm) causes Ga(mu-H)2Ga to isomerize to a
      mixture of HGaGaH and H2GaGa, whereas broad-band visible irradiation (lambda >
      450 nm) of In(mu-H)2In gives rise to the isomer HInInH, together with InH. The
      isomerization can be reversed by UV photolysis (lambda = ca. 365 nm) of HGaGaH,
      H2GaGa, and HInInH or by near-IR photolysis (lambda > 700 nm) of HGaGaH and
      H2GaGa.

PMID- 11960476
TI  - O2 penetration and proton burial depth in proteins: applicability to fold family
      recognition.
AB  - Paramagnetically induced relaxation effects of O2 and the nitroxide 4-hydroxy
      TEMPO were measured for the amide protons of perdeuterated rubredoxin from the
      hyperthermophilic archaeon Pyrococcus furiosus and the mesophilic bacterium
      Clostridium pasteurianum. For both O2 and the impermeant nitroxide, the induced
      relaxation at the static solvent inaccessible amide sites is dominated by long
      range interactions with the paramagnetic species in the bulk aqueous phase. The
      upper bound of O2 solubility in the internal matrix of the rubredoxins is one
      tenth that of the bulk aqueous phase. Furthermore, the difference between the
      oxygen solubilities inside the two rubredoxins is at most 1% that of bulk water
      O2 solubility, suggesting that there are only modest differences in this measure
      of fluidity for the mesophile vs hyperthermophile protein interiors. Calculations
      based on the assumption of a paramagnet uniformly distributed on the protein
      exterior yield accurate predictions at nearly all amide sites for the minimum
      relaxation value observed from either the O2 or nitroxide data. Model
      calculations indicate that the readily obtained paramagnetically induced
      relaxation effects should prove effective in recognition of structural homology
      for proteins that are too widely diverged for sequence-based recognition.

PMID- 11960475
TI  - 59Co solid-state NMR as a new probe for elucidating metal binding in
      polynucleotides.
AB  - Although magnesium fulfills several essential biochemical roles, direct studies
      on this ion are complicated by its unfavorable spectroscopic characteristics.
      This contribution explores the possibility of monitoring magnesium-nucleic acid
      binding via a combination of [Co(NH3)6]3+ as surrogate for [Mg(H2O)6]2+, and of
      high-resolution solid-state 59Co NMR as a spectroscopic probe. Such strategy
      quenches fast cationic exchanges between bound and free states, while exploiting
      the superior NMR properties of the 59Co spin. Experiments on relatively small
      amounts of tRNA can then discern resonances corresponding to different metal
      binding environments. These characterizations were assisted by studies on model
      compounds and by multinuclear 31P-59Co recoupling experiments.

PMID- 11960477
TI  - Hydronium ion complex of 18-crown-6: where are the protons? A density functional
      study of static and dynamic properties.
AB  - A quantum-chemical study employing the BLYP density functional is reported for
      the complex of H3O+ with 18-crown-6. According to a Car-Parrinello molecular
      dynamics (CPMD) study at 340 K, the complex is quite flexible, and is
      characterized by three quasi-linear (two-center) hydrogen-bond interactions for
      most of the time. On a time scale of 10 ps, frequent inversions of H3O+ are
      observed, as well as two 120 degrees rotations switching the hydrogen bonds from
      one set of crown-ether O atoms to the other. These results are consistent with
      density-functional studies of stationary points on the potential energy surface,
      which show how the crown "catalyzes" the guest's inversion. Two close-lying
      minima are characterized, as well as two distinct transition states connecting
      them, either via H3O+ inversion or rotation, with barriers of 1.0 and 4.6
      kcal/mol, respectively, at the BLYP/II'//BLYP/6-31G level. Orbital interactions
      between lone pairs on ether O atoms and hydronium sigma(OH) antibonding orbitals
      are important factors for the directionality of the hydrogen bonds.

PMID- 11960478
TI  - An NMR and quantum-mechanical investigation of tetrahydrofuran solvent effects on
      the conformational equilibria of 1,4-butanedioic acid and its salts.
AB  - Vicinal proton-proton NMR couplings have been used to compare the influences of
      water and tetrahydrofuran (THF) as solvents on the conformational equilibria of
      1,4-butanedioic (succinic) acid and its mono- and dianionic salts. An earlier NMR
      investigation (Lit, E. S.; Mallon, F. K.; Tsai, H. Y.; Roberts, J. D. J. Am Chem.
      Soc. 1993, 115, 9563-9567) showed that, in water, the conformational preferences
      for the gauche conformations for butanedioic acid and its monoanion and dianion
      were, respectively, approximately 84%, 66%, and 43%, essentially independent of
      the nature of the cation or concentration. We now report the corresponding gauche
      percentages calculated in the same way for 0.05 M solutions in THF to be 66%, 90
      100%, and 46-64%. Substantial evidence was adduced for the rotational angle
      between the substituents in the monoanion being approximately 70 degrees. The
      positions of conformational equilibria of the salts in THF, particularly of the
      dianion, were found to be rather insensitive to concentration and temperature,
      but more sensitive to the amount of water present. Ab initio quantum-mechanical
      calculations for 1,4-butanedioate dianion indicate that, as expected for the gas
      phase, the trans conformation of the dianion should be heavily favored over the
      gauche, but, in both THF and water, the gauche conformation is calculated to
      predominate with rotational angles substantially less than 60 degrees. This
      conclusion is, in fact, generally consistent with the experimental vicinal proton
      couplings, which are wholly inconsistent with the trans conformation.

PMID- 11960479
TI  - Metal-benzene and metal-CO bond energies in neutral and ionic C6H6Cr(CO)3 studied
      by threshold photoelectron-photoion coincidence spectroscopy and density
      functional theory.
AB  - photoelectron-photoion coincidence spectroscopy and density functional theory
      calculations have been used to investigate the dissociation kinetics of the
      benzene chromium tricarbonyl ion, BzCr(CO)3+ (Bz = C6H6). The dissociation of the
      BzCr(CO)3+ ion proceeds by the sequential loss of three CO and benzene ligands.
      The first and third CO and the benzene loss reactions were associated with
      metastable precursor ions (lifetimes in the microsecond range). By simulating the
      resulting asymmetric time-of-flight peak shapes and breakdown diagram, the 0 K
      appearance energies of the four product ions were determined to be 8.33 +/- 0.05,
      8.93 +/- 0.05, 9.97 +/- 0.06, and 11.71 +/- 0.06 eV, respectively. Combined with
      the ionization energy of BzCr(CO)3, 7.30 +/- 0.05 eV, the three successive Cr-CO
      bond energies in the BzCr(CO)3+ were found to alternate, with values of 1.03 +/-
      0.05, 0.60 +/- 0.05, and 1.04 +/- 0.05 eV, respectively, and the Bz-Cr bond
      energy in BzCr+ is 1.74 +/- 0.05 eV, a trend confirmed by the density functional
      theory (DFT) calculations. Using the heats of formation of the fully dissociated
      products, C6H6, Cr+, and CO, the 298 K heats of formation the ionic BzCr(CO)n+ (n
      = 03) species were determined. By scaling the DFT calculated bond energies for
      the neutral molecules, the heats of formation of the neutral BzCr(CO)n (n = 03)
      were also obtained.

PMID- 11960480
TI  - Theoretical study on the stability of N-glycosyl bonds: why does N7-platination
      not promote depurination?
AB  - The depurination reaction of guanosine, protonated or modified with cisplatin at
      the N7 position, has been studied by density functional theory (DFT), coupled
      with a continuum treatment of solvation. Protonation accelerates the depurination
      reaction whereas N7-platination, the initial product of cisplatin binding to DNA,
      does not. The computed reaction energy profiles demonstrate that N7-platination
      has only a minor effect on the energetics of the transition state, whereas
      protonation lowers it by approximately 10 kcal mol(-1). The orbitals involved in
      N7-Pt/H bonding are examined, and electronic differences between the two
      substituted guanines are identified. Natural bond orbital analysis, fragment
      orbital analysis, and extended transition-state theory reveal how the
      electronically different substituents at the N7 position control the stability of
      the N9-C1' bond. The detailed description of the electronic structure of the N7
      substituted guanosines and the computational protocol developed to obtain a
      realistic model for these systems not only explain a longstanding enigma but also
      provide guidelines for further studies toward understanding the interactions of
      cisplatin with DNA.

PMID- 11960481
TI  - Microwave investigation of sulfuric acid monohydrate.
AB  - The complex H2SO4-H2O has been observed by rotational spectroscopy in a
      supersonic jet. A-type spectra for 18 isotopic forms have been analyzed, and the
      vibrationally averaged structure of the system has been determined. The complex
      forms a distorted, six-membered ring with the water unit acting as both a
      hydrogen bond donor and a hydrogen bond acceptor toward the sulfuric acid. One of
      the H2SO4 protons forms a short, direct hydrogen bond to the water oxygen, with
      an H...O distance of 1.645(5) A and an O-H...O angle of 165.2(4) degrees.
      Additionally, the orientation of the water suggests a weaker, secondary hydrogen
      bond between one of the H2O hydrogens and a nearby S=O oxygen on the sulfuric
      acid, with an O...H distance of 2.05(1) A and an O-H...O angle of 130.3(5)
      degrees. The experimentally determined structure is in excellent agreement with
      previously published DFT studies. Experiments with HOD in the jet reveal the
      formation of only isotopomers involving deuterium in the secondary hydrogen bond,
      providing direct experimental evidence for the secondary H...O interaction.
      Extensive isotopic substitution has also permitted a re-determination of the
      structure of the H2SO4 unit within the complex. The hydrogen-bonding OH bond of
      the sulfuric acid elongates by 0.07(2) A relative to that in free H2SO4, and the
      S=O bond involved in the secondary interaction stretches by 0.04(1) A. These
      changes reflect substantial distortion of the H2SO4 moiety in response to only a
      single water molecule, and prior to the proton transfer event. Spectral data
      indicate that the complex undergoes at least one, and probably more than one type
      of internal motion. Although the sulfuric acid in this work was produced from
      direct reaction of SO3 and water in the jet, experiments with H2(18)O indicate
      that about 2-3% of the acid is formed via processes not normally associated with
      the gas-phase hydration of SO3.

PMID- 11960482
TI  - Benzdiynes (1,2,4,5-tetradehydrobenzenes): direct observation by wavelength
      selective photolyses of benzenetetracarboxylic dianhydrides in low-temperature
      nitrogen matrixes.
AB  - Toward direct observation of benzdiynes, we investigated the wavelength-selective
      photolyses of five kinds of benzenetetracarboxylic dianhydride derivatives in
      nitrogen matrixes at 13 K. In the first step of the photolyses, all dianhydrides
      were converted into benzynedicarboxylic anhydrides with loss of CO and CO2 upon
      irradiation at 308 nm. In the second step, the benzyne intermediates were
      photolyzed at 266 nm. In these photolyses, the generation of two kinds of
      benzdiynes, 3,6-difluoro-1,4-benzdiyne and 3,6-bis(trifluoromethyl)-1,4
      benzdiyne, was confirmed by good correspondence between observed and calculated
      IR spectra. These benzdiynes were converted into the corresponding hexatriynes
      upon further irradiation at 266 nm. Benzdiynes were not observed in the
      photolyses of the other three dianhydrides: only hexatriynes were observed as
      major photoproducts. These results suggested that benzdiynes were generated first
      and then converted into hexatriynes and that the efficiency of the decomposition
      of benzdiynes depended on the substituents. The dynamics of the generation and
      decomposition of benzdiynes in the matrixes was analyzed by using a successive
      reaction scheme.

PMID- 11960483
TI  - General framework for studying the dynamics of folded and nonfolded proteins by
      NMR relaxation spectroscopy and MD simulation.
AB  - A general framework is presented for the interpretation of NMR relaxation data of
      proteins. The method, termed isotropic reorientational eigenmode dynamics (iRED),
      relies on a principal component analysis of the isotropically averaged covariance
      matrix of the lattice functions of the spin interactions responsible for spin
      relaxation. The covariance matrix, which is evaluated using a molecular dynamics
      (MD) simulation, is diagonalized yielding reorientational eigenmodes and
      amplitudes that reveal detailed information about correlated protein dynamics.
      The eigenvalue distribution allows one to quantitatively assess whether overall
      and internal motions are statistically separable. To each eigenmode belongs a
      correlation time that can be adjusted to optimally reproduce experimental
      relaxation parameters. A key feature of the method is that it does not require
      separability of overall tumbling and internal motions, which makes it applicable
      to a wide range of systems, such as folded, partially folded, and unfolded
      biomolecular systems and other macromolecules in solution. The approach was
      applied to NMR relaxation data of ubiquitin collected at multiple magnetic fields
      in the native form and in the partially folded A-state using MD trajectories with
      lengths of 6 and 70 ns. The relaxation data of native ubiquitin are well
      reproduced after adjustment of the correlation times of the 10 largest
      eigenmodes. For this state, a high degree of separability between internal and
      overall motions is present as is reflected in large amplitude and collectivity
      gaps between internal and overall reorientational modes. In contrast, no such
      separability exists for the A-state. Residual overall tumbling motion involving
      the N-terminal beta-sheet and the central helix is observed for two of the
      largest modes only. By adjusting the correlation times of the 10 largest modes, a
      high degree of consistency between the experimental relaxation data and the iRED
      model is reached for this highly flexible biomolecule.

PMID- 11960484
TI  - A computational ensemble pharmacophore model for identifying substrates of P
      glycoprotein.
AB  - P-glycoprotein (P-gp) functions as a drug efflux pump, mediating multidrug
      resistance and limiting the efficacy of many drugs. Clearly, identification of
      potential P-gp substrate liability early in the drug discovery process would be
      advantageous. We describe a multiple-pharmacophore model that can discriminate
      between substrates and nonsubstrates of P-gp with an accuracy of 63%. The
      application of this filter allows large virtual libraries to be screened
      efficiently for compounds less likely to be transported by P-gp.

PMID- 11960485
TI  - Structure-based design and synthesis of 2-benzylidene-benzofuran-3-ones as
      flavopiridol mimics.
AB  - Novel 2-benzylidene-benzofuran-3-ones were designed and synthesized to mimic
      flavopiridol, a well-established inhibitor of cyclin-dependent kinases (CDKs)
      which is currently undergoing clinical evaluation. The underlying design concepts
      as well as the synthesis and structure-activity relationships (CDKs 1, 2, and 4
      enzyme assays) of these mimics are described. Inhibitors of CDKs 1 and 2 that are
      more potent and selective than flavopiridol were obtained.

PMID- 11960486
TI  - Exploration of the pharmacophore of 3-alkyl-5-arylimidazolidinediones as new
      CB(1) cannabinoid receptor ligands and potential antagonists: synthesis,
      lipophilicity, affinity, and molecular modeling.
AB  - A set of 29 3-alkyl 5-arylimidazolidinediones (hydantoins) with affinity for the
      human cannabinoid CB(1) receptor was studied for their lipophilicity and
      conformational properties in order to delineate a pharmacophore. These molecules
      constitute a new template for cannabinoid receptor recognition, since (a) their
      structure differs from that of classical cannabinoid ligands and (b) antagonism
      is the mechanism of action of at least three compounds (20, 21, and 23). Indeed,
      in the [(35)S]-GTP gamma S binding assay using rat cerebellum homogenates, they
      behave as antagonists without any inverse agonism component. Using a set of
      selected compounds, experimental lipophilicity was measured by RP-HPLC and
      calculated by a fragmental method (CLOGP) and a conformation-dependent method
      (CLIP based on the molecular lipophilicity potential). These approaches revealed
      two models which differentiate the binding mode of nonpolar and polar hydantoins
      and which could explain, at least for compounds 20, 21, and 23, the mechanism of
      action of this new family of cannabinoid ligands.

PMID- 11960487
TI  - Structure-based design of novel potent nonpeptide thrombin inhibitors.
AB  - The clinical syndromes of thromboembolism are evoked by an excessive stimulation
      of the coagulation cascade. In this context, the serine protease thrombin plays a
      key role. Considerable efforts have therefore been devoted to the discovery of
      safe, orally active inhibitors of this enzyme. On the basis of the X-ray crystal
      structure of the peptide-like thrombin inhibitor NAPAP complexed with bovine
      thrombin, we have designed a new structural class of nonpeptidic inhibitors
      employing a 1,2,5-trisubstituted benzimidazole as the central scaffold. Supported
      by a series of X-ray structure analyses, we optimized the activity of these
      compounds. Thrombin inhibition in the lower nanomolar range could be achieved
      although the binding energy mainly results from nonpolar, hydrophobic
      interactions. To improve in vivo potency, we increased the overall hydrophilicity
      of the molecules by introducing carboxylate groups. The very polar compound 24
      (BIBR 953) exhibited the most favorable activity profile in vivo. This
      zwitterionic molecule was converted into the double-prodrug 31 (BIBR 1048), which
      showed strong oral activity in different animal species. On the basis of these
      results, 31 was chosen for clinical development.

PMID- 11960488
TI  - Vinyl sulfide cyclized analogues of angiotensin II with high affinity and full
      agonist activity at the AT(1) receptor.
AB  - Vinyl sulfide cyclized analogues of the octapeptide angiotensin II that are
      structurally related to the cyclic disulfide agonist c[Hcy(3,5)]Ang II have been
      prepared. The synthesis relies on the reaction of the mercapto group of a
      cysteine residue in position 3 with the formyl group of allysine incorporated in
      position 5 of angiotensin II. A mixture of the cis and the trans isomers was
      formed, and these were separated and isolated by RP-HPLC. Thus, the three-atom
      CH(2)[bond]S[bond]S element of the AT(1) receptor agonist c[Hcy(3,5)]Ang II has
      been displaced by a bioisosteric three-atom S[bond]CH[double bond]CH element. A
      comparative conformational analysis of the 13-membered ring systems of
      c[Hcy(3,5)]Ang II and the 13-membered cyclic vinyl sulfides with cis and trans
      configuration, respectively, suggested that all three systems adopted very
      similar low-energy conformations. This similarity was also reflected in the
      bioactivity. Both of the compounds that contained the ring systems encompassing
      the cis or trans vinyl sulfide elements between positions 3 and 5 exhibited K(i)
      values less than 2 nM and exerted full agonism at the AT(1) receptor. In
      contrast, vinyl sulfide cyclization involving the amino acid residues 5 and 7
      rendered inactive compounds. The cyclic vinyl sulfides that have agonist activity
      were both shown to possess low-energy conformers compatible with the previously
      proposed 3D model for the bioactive conformation of Ang II.

PMID- 11960489
TI  - Binding mode analysis of 3-(4-benzoyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2
      propenamide: a new synthetic histone deacetylase inhibitor inducing histone
      hyperacetylation, growth inhibition, and terminal cell differentiation.
AB  - The binding mode of 3-(4-aroyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamides 1a-c,
      belonging to a recently reported class of synthetic histone deacetylase (HDAC)
      inhibitors (Massa, S.; et al. J. Med. Chem. 2001, 44, 2069-2072), into the new
      modeled HDAC1 catalytic core is presented, and enzyme/inhibitor interactions are
      discussed. HDAC1 X-ray coordinates were obtained by virtual "mutation" of those
      of histone deacetylase-like protein, a bacterial HDAC homologue. In in vitro
      antimaize HD2 as well as antimouse HDAC1 assay, compounds 1a-c showed inhibitory
      activities in the low micromolar range. Similarly, 1a-c are endowed with anti
      HDAC activity in vivo: on mouse A20 cells, 1a-c induced histone hyperacetylation
      leading to a highly increased acetylation level of H4 as compared to control
      histones. Results obtained with acid-urea-triton polyacrylamide gel
      electrophoresis have been confirmed by Western Blot experiments. Finally,
      compound 1a, chosen as a representative member of this class of HDAC inhibitors,
      resulted endowed with antiproliferative (45 and 85% cell growth inhibition at 40
      and 80 microM, respectively) and cellular differentiation (18 and 21% of
      benzidine positive cells at the same concentrations) activities in murine
      erythroleukemic cells.

PMID- 11960490
TI  - Investigation of potential bioisosteric replacements for the carboxyl groups of
      peptidomimetic inhibitors of protein tyrosine phosphatase 1B: identification of a
      tetrazole-containing inhibitor with cellular activity.
AB  - Protein tyrosine phosphatases (PTPs) constitute a diverse family of enzymes that,
      together with protein tyrosine kinases, control the level of intracellular
      tyrosine phosphorylation, thus regulating many cellular functions. PTP1B
      negatively regulates insulin signaling, in part, by dephosphorylating key
      tyrosine residues within the regulatory domain of the beta-subunit of the insulin
      receptor, thereby attenuating receptor kinase activity. Inhibitors of PTP1B would
      therefore have the potential of prolonging the phosphorylated (activated) state
      of the insulin receptor and are anticipated to be a novel treatment of the
      insulin resistance characteristic of type 2 diabetes. We previously reported a
      series of small molecular weight peptidomimetics as competitive inhibitors of
      PTP1B, with the most active analogues having K(i) values in the low nanomolar
      range. Furthermore, we confirmed that the O-carboxymethyl salicylic acid moiety
      is a remarkably effective novel phosphotyrosine mimetic. Because of the low cell
      permeability of this compound class, it was important to investigate the
      possibility of replacing one or both of the remaining carboxyl groups while
      maintaining PTP1B inhibitory activity. The analogues described herein further
      support the importance of an acidic functionality at both positions of the
      tyrosine head moiety. An important discovery was the ortho tetrazole analogue 29
      (K(i) = 2.0 microM), which was equipotent to the dicarboxylic acid analogue 2
      (K(i) = 2.0 microM). Solution of the X-ray cocrystal structure of the ortho
      tetrazole analogue 29 bound to PTP1B revealed that the tetrazole moiety is well
      accommodated in the active site and binds in a fashion similar to the ortho
      carboxylate analogue 2 reported previously. This novel monocarboxylic acid
      analogue revealed significantly higher Caco-2 cell permeability as compared to
      all previous compounds. Furthermore, compound 29 exhibited modest enhancement of
      insulin-stimulated 2-deoxyglucose uptake by L6 myocytes.

PMID- 11960491
TI  - Identification of nonpeptidic urotensin II receptor antagonists by virtual
      screening based on a pharmacophore model derived from structure-activity
      relationships and nuclear magnetic resonance studies on urotensin II.
AB  - The vasoactive cyclic 11-amino acid peptide urotensin II (U-II) has recently been
      discovered as the endogenous ligand of the orphan G-protein-coupled receptor
      GPR14. As U-II might be involved in the regulation of cardiovascular homeostasis
      and pathology, a nonpeptidic GPR14/U-II antagonist is of considerable basic and
      therapeutic interest. We have performed structure-activity relationship studies
      on U-II by investigating 25 peptide analogues to mobilize intracellular calcium
      in GPR14-transfected CHO cells, demonstrating that only the side chains of the
      residues Trp-7, Lys-8, and Tyr-9 are required for receptor recognition and
      activation. The solution structure of U-II derived by nuclear magnetic resonance
      has served as a structural template for a three-dimensional three point
      pharmacophore query for the virtual screening of the Aventis compound repository
      for nonpeptidic U-II receptor antagonists. Highly active lead compounds of six
      different scaffold classes could be identified, antagonizing the biological
      activity of U-II in vitro. The most potent compound identified by the virtual
      screening approach, 1-(3-carbamimidoyl-benzyl)-4-methyl-1H-indole-2-carboxylic
      acid (naphthalen-1-ylmethyl)amide, reveals an IC(50) of 400 nM in a functional
      fluorometric imaging plate reader assay and constitutes a promising lead.

PMID- 11960492
TI  - Cyclodextrin-derived host molecules as reversal agents for the neuromuscular
      blocker rocuronium bromide: synthesis and structure-activity relationships.
AB  - A series of mono- and per-6-substituted cyclodextrin derivatives were synthesized
      as synthetic receptors (or host molecules) of rocuronium bromide, the most widely
      used neuromuscular blocker in anaesthesia. By forming host-guest complexes with
      rocuronium, these cyclodextrin derivatives reverse the muscle relaxation induced
      by rocuronium in vitro and in vivo and therefore can be used as reversal agents
      of the neuromuscular blocker to assist rapid recovery of patients after surgery.
      Because this supramolecular mechanism of action does not involve direct
      interaction with the cholinergic system, the reversal by these compounds, e.g.,
      compound 14 (Org 25969), is not accompanied by cardiovascular side effects
      usually attendant with acetylcholinesterase inhibitors such as neostigmine. The
      structure-activity relationships are consistent with this supramolecular
      mechanism of action and are discussed herein. These include the effects of
      binding cavity size and hydrophobic and electrostatic interaction on the reversal
      activities of these compounds.

PMID- 11960493
TI  - Polysaccharide-oligoamine based conjugates for gene delivery.
AB  - This work describes a versatile and universal polycation system based on
      oligoamines grafted on natural polysaccharides that is capable of complexing
      various plasmids and administering them into various cells in high yield to
      produce a desired protein. These polycations are expected to better meet the
      requirements for effective complexation and delivery of plasmid or an antisense
      and to biodegrade into nontoxic components at a controlled rate. The developed
      biodegradable polycations are based on spermine, a natural tetramine, conjugated
      to dextran or arabinogalactan. These polycations were prepared by reductive
      amination of oxidized polysaccharides with the desired oligoamines. The Schiff
      base conjugates thus obtained were reduced to the stable amine conjugates by
      sodium borohydride. Over 300 different polycations were prepared starting from
      various polysaccharides and oligoamines, mainly oligoamines of two to four amino
      groups. Although most of these conjugates formed stable complexes with various
      plasmids as determined by turbidity experiments, only a few polycations were
      found to be active in transfecting cells. This work indicates that the structure
      of the polycation plays a significant role in the transfection activity of
      polycations.

PMID- 11960494
TI  - Rational design, synthesis, and biological activity of novel conformationally
      restricted vitamin D analogues, (22R)- and (22S)-22-ethyl-1,25-dihydroxy-23,24
      didehydro-24a,24b-dihomo-20-epivitamin D(3).
AB  - Two new vitamin D analogues, (22R)- and (22S)-22-ethyl-1,25-dihydroxy-23,24
      didehydro-24a,24b-dihomo-20-epivitamin D(3) (3 and 4), were rationally designed
      on the basis of the active space group concept previously proposed by us. The 22R
      ethyl group of 3 restricts the mobility of the side chain to active space
      regions, whereas the 22S ethyl group of 4 confines the side chain to an inactive
      region. The double bond at C(23) further restricts the side chain flexibility.
      These compounds (3 and 4) were synthesized using ortho ester Claisen
      rearrangement as the key step. As expected, the 22R isomer 3 has nearly 100 times
      higher efficacy than 1,25-dihydroxyvitamin D(3) (1) in cell differentiation,
      although its affinity for the vitamin D receptor (VDR) was one-seventh of that of
      1. The 22S isomer 4 has significantly lower efficacy than 3. A docking study in
      combination with site-directed mutation analysis revealed that two carbon
      elongated side chain analogue 3 could be fitted in the ligand binding pocket of
      the VDR by adopting a stable conformation.

PMID- 11960495
TI  - Preparation and characterization of platinum(II) and (IV) complexes of 1,3
      diaminepropane and 1,4-diaminebutane: circumvention of cisplatin resistance and
      DNA interstrand cross-link formation in CH1cisR ovarian tumor cells.
AB  - The reaction of Pt(dimethyl sulfoxide)(2)CBDCA (CBDCA = 1,1
      cyclobutanedicarboxylate) with 1,4-diaminebutane and 1,3-diaminepropane ligands
      yields, under certain conditions, new [Pt(diamine)(2)]CBDCA complexes (1a,b),
      where the CBDCA ligand has been removed from the coordination sphere of the
      platinum atom by the diamine ligand, instead of forming the expected
      [Pt(diamine)CBDCA] complexes (1'a,b). The structure of complexes 1a and 1'b was
      solved by X-ray diffraction. Complex 1a crystallizes in the orthorhombic system,
      in the noncentrosymmetric C222 space group, with unit cell parameters: a =
      20.053(2) A; b = 8.655(2) A, c = 5.711(3) A; V = 991.2(6) A(3); delta (calcd) =
      1.627 mg/m(3); and R = 0.050. The Pt atom displays an unexpected distorted
      tetrahedral coordination with a N-Pt-N inner bond angle equal to 81(2) degrees
      for N atoms of the same 1,3-propanediamine ligand and a N-Pt-N bond angle for
      different ligands equal to 135.4(9) degrees. Complex 1'b crystallizes in the
      monoclinic system, in the centrosymmetric P2(1)/c space group, with unit cell
      parameters: a = 6.007(2) A; b = 15.336(4) A, c = 13.232(5) A; beta = 101.90(3)
      degrees; V = 1192.8(7) A(3); delta (calcd) = 2.369 mg/m(3); and R = 0.067.
      Cytotoxicity data show that of all the synthesized compounds, only complexes 1'a
      and 1'b exhibit remarkable cytotoxic properties. Thus, in contrast with
      carboplatin (cis-diammine-1,1-cyclobutane dicarboxilatoplatinum(II)), compounds
      1'a and 1'b, which also contain the CBDCA ligand, are able to circumvent
      cisplatin (cis-diamminedichloroplatinum(II)) resistance in several tumor cells.
      Moreover, after 24 h of incubation of CH1cisR ovarian tumor cells with 10 microM
      of compounds 1'a and 1'b, the level of DNA interstrand cross-links (ICLs) induced
      by compounds 1'a and 1'b is 3.3 and 3.8 times higher, respectively, than that of
      carboplatin and 3.5 and 4.0 times higher, respectively, than that of cisplatin.
      Interestingly, under the same conditions, the intracellular accumulation of
      compounds 1'a and 1'b is similar to that of carboplatin and cisplatin. However,
      the extent of binding to DNA of compounds 1'a and 1'b is similar to that of
      cisplatin but slightly higher than that of carboplatin. We propose that
      circumvention of cisplatin resistance in CH1cisR cells by compounds 1'a and 1'b
      might be related to its higher ability to form DNA ICLs relative to carboplatin
      and cisplatin.

PMID- 11960496
TI  - 5'-Deoxy congeners of 9-(3-amido-3-deoxy-beta-D-xylofuranosyl)-N(6)
      cyclopentyladenine: new adenosine A(1) receptor antagonists and inverse agonists.
AB  - The synthesis and structure-activity relationship of N(6)-cyclopentyl-3'
      substituted-xylofuranosyladenosine analogues with respect to various adenosine
      receptors were explored in order to identify selective and potent antagonists and
      inverse agonists for the adenosine A(1) receptor. In particular, the effects of
      removal of the 5'-OH group and introduction of selected substituents at the 3'
      NH(2) position of 9-(3-amino-3-deoxy-beta-D-xylofuranosyl)-N(6)
      cyclopentyladenine were probed. A solid phase-assisted synthetic approach was
      used to optimize the 3'-amide functionality. In view of the general concern of
      the presence of a 5'-OH moiety with regard to cellular toxicity, the present
      study describes 5'-deoxy compounds with reasonable affinity for the human
      adenosine A(1) receptor. Interestingly, this study shows that optimization of the
      3'-"up" amide substituent can substantially compensate for the drop in affinity
      for the adenosine A(1) receptor, which is generally observed upon removal of the
      5'-OH group. The fact that for several 3'-amido-substituted (5'-deoxy)-N(6)
      cyclopentyladenosine derivatives, guanosine 5'-triphosphate-induced shifts in
      K(i) values were significantly lower than 1 implies that these analogues behave
      as inverse agonists. This is further supported by their 1,3-dipropyl-8
      cyclopentylxanthine-like capacity to increase forskolin-induced adenosine cyclic
      3',5'-phosphate production.

PMID- 11960497
TI  - Synthesis of nitroindole derivatives with high affinity and selectivity for
      melatoninergic binding sites MT(3).
AB  - The aim of this study was to synthesize selective ligands for melatoninergic
      subtype receptors that could elucidate the physiological role of melatonin (N
      acetyl-5-methoxytryptamine, 1). So, we first investigated the role of a nitro
      substituent in the 4-, 6-, or 7-position of the indole heterocycle. Comparatively
      to melatonin, its analogues that nitrated in the 6- or 7-position (6 and 22) lose
      MT(3) but retain good MT(1) and MT(2) affinities, whereas the 4-nitro isomer (5)
      shows very high affinity (nanomolar) and selectivity for the MT(3) binding sites.
      N-Methylation of the indole nucleus of compound 5 potentiates these effects and
      affords the most potent and selective MT(3) ligand (17). The 2-iodo derivatives
      (12 and 10) of compounds 5 and 17 have also been synthesized to evaluate their
      binding profile with a view to further develop MT(3) selective radioligands.

PMID- 11960498
TI  - Structure-activity relationships of methoctramine-related polyamines as muscular
      nicotinic receptor noncompetitive antagonists. 2. Role of polymethylene chain
      lengths separating amine functions and of substituents on the terminal nitrogen
      atoms.
AB  - Polymethylene tetraamine methoctramine (1) is a prototypical antimuscarinic
      ligand endowed with a significant affinity for muscular nAChRs. Thus, according
      to the universal template approach, structural modifications were performed on 1
      in order to improve affinity and selectivity for the muscle-type nAChR. The
      polyamine derivatives synthesized were tested at both frog rectus and Torpedo
      nAChRs and at guinea pig left atria (M(2)) and ileum longitudinal muscle (M(3))
      mAChRs. All of the compounds, like prototype 1, were noncompetitive antagonists
      of nicotinic receptors while being competitive antagonists at M(2) and M(3)
      mAChRs. The biological profile of polyamines 4-7 revealed that increasing the
      number of amine functions and the chain length separating these nitrogen atoms
      led to a significant improvement in potency at nAChRs. Moreover, the role of the
      number and type of amine functions in the interaction with nAChRs was further
      investigated through the synthesis of compounds 9 and 10. Tetraamines 8 and 11,
      bearing a rather rigid spacer between the nitrogen atoms instead of the very
      flexible polymethylene chain, displayed a profile similar to that of 1 at nAChRs,
      whereas a significant decrease in potency was observed at mAChRs. Tetraamine 12,
      bearing a 2-methoxyphenethyl group, was less potent than 1, whereas tetraamine
      13, carrying a diphenylethyl moiety, was more potent than 1, confirming that an
      increase in size of the hydrophobic group on the terminal nitrogen atoms
      increases significantly the binding affinity for nAChRs. Tetraamines 14-17 were
      significantly more potent than prototype 2 at both frog rectus and Torpedo
      nAChRs, confirming that an increase in the distance between the amine functions
      results in a parallel increase in the affinity for nAChRs. To gain insight into
      the mode of interaction of polymethylene tetraamines with nAChRs, photolabile (19
      and 20) and fluorescent (21 and 22) compounds were synthesized. A most intriguing
      finding was the observation that 19, which bears two identical azido groups on
      the terminal nitrogen atoms, was found to bind the Torpedo nAChR with a 1:1
      stoichiometry, suggesting a U-shaped conformation in the receptor interaction.
      Moreover, the high potency shown by fluorescent compounds 21 and 22 appears
      promising for a further characterization of the polymethylene tetraamines binding
      site with the muscle-type nAChR.

PMID- 11960499
TI  - Halogenated diazirines as photolabel mimics of the inhaled haloalkane
      anesthetics.
AB  - The inhaled anesthetics are low affinity volatile compounds whose mechanism of
      action remains unclear, in part due to the difficulty of determining their
      binding targets. Photolabeling may help resolve this difficulty, and thus we have
      synthesized six compounds (four previously unreported) with structural and
      physical similarity to halothane (1-bromo-1-chloro-2,2,2-trifluoroethane), a
      commonly used clinical anesthetic. These compounds incorporate either a diazo,
      diazirine, or azido group to provide photolability in the long-UV range and to
      provide a highly reactive photolysis product. While several of the compounds have
      immobilizing activity in tadpoles, it is complicated by either toxicity or very
      low potency. One compound however, a halogenated three-carbon diazirine 4, is a
      potent anesthetic, is apparently nontoxic, potentiates GABA(A) Cl(-) currents,
      and stabilizes serum albumin, all of which are features of halothane. When tagged
      with radioactivity, this compound should serve as a reasonable probe of
      haloalkane anesthetic binding targets and sites.

PMID- 11960500
TI  - 3-Heteroaryl-2-pyridones: benzodiazepine site ligands with functional delectivity
      for alpha 2/alpha 3-subtypes of human GABA(A) receptor-ion channels.
AB  - A novel series of 3-heteroaryl-5,6-bis(aryl)-1-methyl-2-pyridones were developed
      with high affinity for the benzodiazepine (BZ) binding site of human gamma
      aminobutyric acid (GABA(A)) receptor ion channels, low binding selectivity for
      alpha 2- and/or alpha 3- over alpha 1-containing GABA(A) receptor subtypes and
      high binding selectivity over alpha 5 subtypes. High affinity appeared to be
      associated with a coplanar conformation of the pyridone and sulfur-containing 3
      heteroaryl rings resulting from an attractive S.O intramolecular interaction.
      Functional selectivity (i.e., selective efficacy) for alpha 2 and/or alpha 3
      GABA(A) receptor subtypes over alpha1 was observed in several of these compounds
      in electrophysiological assays. Furthermore, an alpha 3 subtype selective inverse
      agonist was proconvulsant and anxiogenic in rodents while an alpha 2/alpha 3
      subtype selective partial agonist was anticonvulsant and anxiolytic, supporting
      the hypothesis that subtype selective BZ site agonists may provide new anxiolytic
      therapies.

PMID- 11960501
TI  - Synthesis and biological evaluation of structurally highly modified analogues of
      the antimitotic natural product curacin A.
AB  - Structure-activity relationship analysis of synthetic analogues of curacin A
      revealed the lack of activity of traditional heterocyclic replacements of the
      thiazoline ring or cyclopropyl analogues of the core diene segment. The
      significance of the C(3)-C(4)-(Z)-alkene geometry was established, and a novel
      oxime analogue was designed that displays biological properties that are a close
      match of the natural product lead. The much less lipophilic, structurally
      simplified oxime 50 was only slightly weaker at inhibiting the growth of cultured
      human tumor cells than the natural product and was found to be more potent than
      curacin A at inhibiting the assembly of purified tubulin. Accordingly, the oxime
      moiety is likely to serve as a novel bioisostere of the (Z)-alkene group.

PMID- 11960502
TI  - 6-[2-(Phosphonomethoxy)alkoxy]pyrimidines with antiviral activity.
AB  - 6-Hydroxypyrimidines substituted at positions 2 and 4 by hydrogen, methyl, amino,
      cyclopropylamino, dimethylamino, methylsulfanyl, or hydroxyl group afford by the
      reaction with diisopropyl 2-(chloroethoxy)methylphosphonate in the presence of
      NaH, Cs(2)CO(3), or DBU a mixture of N(1)- and O(6)-[2
      (diisopropylphosphorylmethoxy)ethyl] isomers which were converted to the free
      phosphonic acids by treatment with bromotrimethylsilane followed by hydrolysis.
      Analogously, 2,4-diamino-6-hydroxypyrimidine gave on reaction with [(R)- and (S)
      2-(diisopropylphosphorylmethoxy)propyl] tosylate, followed by deprotection, the
      enantiomeric 6-[2-(phosphonomethoxy)propoxy]pyrimidines. 2,4-Diamino-6
      sulfanylpyrimidine gave, on treatment with diisopropyl 2
      (chloroethoxy)methylphosphonate in the presence of NaH and subsequent
      deprotection, 2,4-diamino-6-[[2-(phosphonomethoxy)ethyl]sulfanyl]pyrimidine. 2
      Amino-4-hydroxy-6-[2-(phosphonomethoxy)ethyl]pyrimidine was obtained from the
      appropriate 2-amino-4-chloropyrimidine derivative by alkaline hydrolysis and
      ester cleavage. Direct alkylation of 2-amino-4,6-dihydroxypyrimidine afforded a
      mixture of 2-amino-4,6-bis[2-(phosphonomethoxy)ethyl]- and 2-amino-1,4-bis[2
      (phosphonomethoxy)ethyl]pyrimidine. None of the N(1)-[2-(phosphonomethoxy)ethyl]
      isomers exhibited any antiviral activity against DNA viruses or RNA viruses
      tested in vitro. On the contrary, the O(6)-isomers, namely the compounds derived
      from 2,4-diamino-, 2-amino-4-hydroxy-, or 2-amino-4-[2-(phosphonomethoxy)ethoxy]
      6-hydroxypyrimidine, inhibited the replication of herpes viruses [herpes simplex
      type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and
      cytomegalovirus (CMV)] and retroviruses [Moloney sarcoma virus (MSV) and human
      immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2)], their activity being
      most pronounced against the latter. The antiviral activity was lower if the
      oxygen at the position 6 was replaced by a sulfur atom, as in 2,4-diamino-6-[2
      (phosphonomethoxy)ethylsulfanyl]pyrimidine. In analogy to N(9)-[2
      (phosphonomethoxy)propyl]-2,6-diaminopurine (PMPDAP), solely the (R)-2,4-diamino
      6-[2-(phosphonomethoxy)propoxy]pyrimidine exerted antiviral activity, whereas its
      (S)-enantiomer was essentially inactive.

PMID- 11960504
TI  - Synthesis of N-[4-[1-ethyl-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]
      L-glutamic acid as an antifolate.
AB  - N-[4-[1-Ethyl-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic
      acid 3 was designed and synthesized to investigate the effect of homologation of
      a C9-methyl to an ethyl on dihydrofolate reductase (DHFR) inhibition and on
      antitumor activity. Compound 3 was obtained via a concise seven step synthesis
      starting from palladium-catalyzed carbonylation of 4-propionylphenol, followed by
      a Wittig reaction with 2,4-diamino-5-(chloromethyl)furo[2,3-d]pyrimidine (6),
      catalytic hydrogenation, hydrolysis, and standard peptide coupling with diethyl L
      glutamate. The biological results indicated that extending the C9-methyl group to
      an ethyl on the C8-C9 bridge region (analogue 3) doubled the inhibitory potency
      against recombinant human (rh) DHFR (IC(50) = 0.21 microM) as compared to the C9
      methyl analogue 1 and was 4-fold more potent than the C9-H analogue 2. As
      compared to 1, compound 3 demonstrated increased growth inhibitory potency
      against several human tumor cell lines in culture with GI(50) values < 1.0 x 10(
      8) M. Compound 3 was also a weak inhibitor of rh thymidylate synthase. Compounds
      1 and 3 were efficient substrates of human folylpolyglutamate synthetase (FPGS).
      Further evaluation of the cytotoxicity of 3 in methotrexate-resistant CCRF-CEM
      cell sublines and metabolite protection studies implicated DHFR as the primary
      intracelluar target. Thus, alkylation of the C9 position in the C8-C9 bridge of
      the classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidine is highly conducive
      to DHFR and tumor inhibitory activity as well as FPGS substrate efficiency.

PMID- 11960503
TI  - Further studies on conformationally constrained tricyclic tropane analogues and
      their uptake inhibition at monoamine transporter sites: synthesis of (Z)-9
      (substituted arylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes as a novel class
      of serotonin transporter inhibitors.
AB  - A novel series of conformationally constrained tricyclic tropane analogues, (Z)-9
      (substituted arylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes, were prepared,
      and their abilities to inhibit high-affinity uptake of dopamine (DA), serotonin
      (5-HT), and norepinephrine (NE) into rat brain nerve endings (synaptosomes) were
      evaluated. First, a systematic screening of a variety of different substituents
      on the phenyl ring indicated that the substitution pattern plays an important
      role in the monoamine transporter activity. Most compounds in this series
      possessed a very low activity at the DA transporter (DAT) but a good to excellent
      affinity for the 5-HT transporter (SERT). In the case of para-substituted phenyl
      analogues, the electronic character of the substituent did not affect uptake
      inhibition as dramatically as observed in some benztropine analogues. Among these
      compounds, the 4-bromophenyl and 4-isopropylphenyl analogues 8d and 8j exhibited
      the highest potency at the SERT with a K(i) value of 10 nM. In the 3,4
      disubstituted phenyl series, even more potent and highly selective compounds were
      discovered. Compound 8o has a K(i) value of 2.3 nM for uptake inhibition at the
      SERT, a DAT/SERT uptake ratio of 2360, and a NET/SERT uptake ratio of 200.
      Compound 8p exhibited a K(i) value of 1.8 nM for uptake inhibition at the SERT, a
      DAT/SERT uptake ratio of 1740, and a NET/SERT uptake ratio of 151. These
      compounds are 3-4-fold more potent than the antidepressant medication fluoxetine,
      and the selectivities for SERT over DAT and NET are also better than those of
      fluoxetine. Second, a variety of functional modifications on the ester moiety
      were investigated. Substitution by other esters or amides as well as alkenes did
      not increase potency, while most of the acetates or benzoates (16-21, 23, and 24)
      and the ketone 28 exhibited significantly improved activity. A good hydrogen
      bonding ability of the substituent is believed to be required for high activity.
      The most potent and selective ligand is compound 23, which displayed a K(i) value
      of 0.06 nM and has essentially no activity at the DAT or NET. The present results
      have important implications for drug addiction as well as a number of psychiatric
      diseases.

PMID- 11960505
TI  - Studies on the synthesis and opioid agonistic activities of mitragynine-related
      indole alkaloids: discovery of opioid agonists structurally different from other
      opioid ligands.
AB  - Mitragynine (1) is a major alkaloidal component in the Thai traditional medicinal
      herb, Mitragyna speciosa, and has been proven to exhibit analgesic activity
      mediated by opioid receptors. By utilizing this natural product as a lead
      compound, synthesis of some derivatives, evaluations of the structure-activity
      relationship, and surveys of the intrinsic activities and potencies on opioid
      receptors were performed with guinea pig ileum. The affinities of some compounds
      for mu-, delta-, and kappa-receptors were determined in a receptor binding assay.
      The essential structural moieties in the Corynanthe type indole alkaloids for
      inducing the opioid agonistic activity were also clarified. The oxidative
      derivatives of mitragynine, i.e., mitragynine pseudoindoxyl (2) and 7
      hydroxymitragynine (12), were found as opioid agonists with higher potency than
      morphine in the experiment with guinea pig ileum. In addition, 2 induced an
      analgesic activity in the tail flick test in mice.

PMID- 11960510
TI  - Increasing incidence of type 2 diabetes in children and adolescents: treatment
      considerations.
AB  - The emerging public health problem of type 2 diabetes in youth reflects
      increasing rates of childhood obesity. As in adults, type 2 diabetes in children
      is part of the insulin resistance syndrome that includes hypertension,
      dyslipidemia and other atherosclerosis risk factors, and hyperandrogenism seen as
      premature adrenarche and polycystic ovary syndrome. Studies in children document
      risk factors for type 2 diabetes and associated cardiovascular risk factors,
      including obesity, family history, diabetic gestation, and underweight or
      overweight for gestational age. Genetically determined insulin resistance, or
      limited beta-cell reserve, has been demonstrated in high risk individuals. This
      genetic background, considered advantageous in a feast and famine existence (the
      thrifty genotype), is rendered detrimental with abundant food and physical
      inactivity, a lifestyle demonstrated to be typical of families of children with
      type 2 diabetes. Case finding in high risk individuals who are asymptomatic may
      be an appropriate response to the public health challenge of type 2 diabetes in
      children, because risk factors for cardiovascular disease are already present at
      the time of diagnosis. Treatment is dictated by the degree of metabolic
      derangement and symptoms. The only data on the use of oral hypoglycemic agents in
      children has been with metformin. Prevention efforts will require community and
      government involvement to reduce obesity and increase physical activity in the
      child, as well as adult, population.

PMID- 11960511
TI  - Should pediatric patients with hyperlipidemia receive drug therapy?
AB  - Hyperlipidemia is now established as a major risk factor for causation of
      coronary heart disease (CHD) in adults; however, there is much debate on the
      level of coronary risk at which lipid-lowering drugs should be used. These issues
      of possible harm or lack of benefit from long-term use of lipid-lowering therapy,
      and cost effectiveness, are also pertinent in the pediatric setting. Evidence
      from several countries indicates that children have an increasing prevalence of
      obesity, hyperlipidemia and type 2 diabetes mellitus. Children who have high
      serum lipids 'track' these increased levels into adulthood. In some countries
      there is a trend to screen children for hypercholesterolemia. Family history
      itself is a poor discriminator in determining which children need to be screened
      and treated. Estimation of apolipoprotein B and/or apolipoprotein E genotype can
      improve prediction. Measuring high density lipoprotein cholesterol also helps,
      but obesity appears to be the best marker for screening children at high risk.
      These considerations should not cloud the need for case finding and treatment of
      children with genetic disorders. Low fat diets have been shown to be well
      tolerated and effective in children; however, there are no major long-term
      studies demonstrating harm or benefit in those on lipid-lowering drugs.
      Nevertheless, concerns regarding the psychological effect and the theoretical
      metabolic effects of long-term lipid lowering remain. Lipid-lowering drugs should
      be generally restricted to children with genetic disorders of lipid metabolism.
      Children with diabetes mellitus, hypertension or nonlipid-related inherited
      disorders leading to premature CHD in adults should be treated with diet, and
      with lipid-lowering drugs when they reach adulthood. Children with secondary
      hyperlipidemia should be assessed individually. A number of drugs and
      nutriceuticals are available for use in children, but only a few drugs are
      licensed for use in children.

PMID- 11960514
TI  - Ethical issues in including pediatric cancer patients in drug development trials.
AB  - Since the biology, pharmacology and toxicology of pediatric cancer is so
      different from cancer in adults, it is impossible to extrapolate from adult
      cancer experience; however, conducting studies in children with cancer is
      ethically and clinically very complex. This is especially so in phase 1 trials,
      aimed at dose finding for new modalities, where the chances to cure the child who
      failed standard therapy are marginal to non-existent. Hence, the child may be
      exposed to risks and discomfort which may be unbalanced by potential benefits.
      This situation, which is difficult for consenting adults, is much more complex
      when a parent gives proxy consent. This review addresses the ethical and clinical
      framework of such studies in the most vulnerable of children.

PMID- 11960512
TI  - Management of croup.
AB  - Croup, or laryngotracheobronchitis, is a common childhood illness most often
      caused by viral infections. It is usually a benign, self-limiting disease, but
      can result in life-threatening upper airway obstruction. Until recently, it was
      not uncommon for children with severe croup to be admitted to intensive care for
      intubation. Management used to be limited to supportive measures, including mist
      therapy. The use of corticosteroids in patients with croup was controversial for
      many years but has, in the last decade, transformed the management of this
      disorder. Although corticosteroids do not alter the history of the viral
      infection, an adequate dose of oral or parenteral dexamethasone or nebulized
      budesonide has been shown to have a beneficial effect on the symptoms of croup.

PMID- 11960513
TI  - Treatment options for juvenile-onset systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an inflammatory chronic disease
      characterized by the presence of activated helper T-cells that induce a B-cell
      response, resulting in the secretion of pathogenic autoantibodies and the
      formation of immune complexes. SLE in children is a disease of low prevalence
      with a wide range of clinical manifestations, which means that the number of
      randomized controlled studies are few and usually involve a small number of
      patients. In recent years, new therapeutic agents have appeared and the role of
      older treatments has been clarified. Many of these treatments are designed to
      reduce inflammation. The spectrum is broad and ranges from traditional
      nonsteroidal anti-inflammatory drugs (NSAIDs) to cytotoxic agents that have anti
      inflammatory effects. The current treatment of children or adults depends on the
      clinical expression of the disease. Minor manifestations usually respond to the
      administration of NSAIDs, low doses of corticosteroids, hydroxychloroquine, or
      methotrexate. Thalidomide could be used for refractory skin lesions. Major
      manifestations can endanger the patient's life and require early, aggressive
      treatment. Kidney disease and other manifestations have been related to the
      formation or deposit of tissular immune complexes. Therefore, for years the main
      aim of treatment has been to suppress the immune response. The immunosuppressant
      treatments used in children with SLE include high doses of corticosteroids,
      azathioprine, methotrexate, cyclosporine, and cyclophosphamide. Several
      combinations of medications have been used to obtain a rapid remission or to
      reduce the risk of toxicity of prolonged administration of cytotoxic agents.
      Intravenous gamma-globulin has been successfully used in the treatment of lupus
      nephritis, vasculitis, and acute thrombocytopenia. In spite of numerous published
      studies, the use of these drugs is still controversial. The immunosuppression
      achieved with these treatments is nonspecific, not always effective, and
      associated with significant toxicities; the most significant being growth
      retardation, accelerated atherosclerosis and severe infectious complications. The
      purpose of new biological therapies is to achieve specific immunosuppression,
      which makes it possible to design more effective and less toxic therapeutic
      strategies. Mycophenolate mofetil is a promising alternative in patients who do
      not respond to high doses of cyclophosphamide or azathioprine. Some recently
      developed monoclonal antibodies such as anti-CD40L or anti-IL-10, or other
      molecules such as LJP394 may prove useful in the near future. Finally, stem cell
      transplantation may be proposed in patients with severe juvenile-onset SLE who do
      not respond to any treatment.

PMID- 11960516
TI  - The most powerful therapeutic force.

PMID- 11960515
TI  - Exercise-induced asthma in children.
AB  - Exercise-induced asthma (EIA) is a relatively common problem in children, but may
      not be recognized because children either do not report their symptoms, or avoid
      activities that cause it. Clarifying the diagnosis of EIA, in particular
      separating EIA from other causes of exertional dyspnea, is essential. Treating
      EIA in children is challenging because of the nature of their physical
      activities, which are often not planned, and may be prolonged. Keeping children
      active is an important goal to ensure healthy physical and social development.
      Many children with EIA are well managed with an inhaled short-acting beta(2)
      adrenoceptor agonist before exercise or if symptoms develop. The approach to more
      troublesome EIA depends on whether the child has persistent asthma and requires
      better prevention, or the EIA is an isolated clinical problem. The options for
      treatment also depend on the timing, frequency, and duration of activity that
      induces EIA. Options include the addition of a cromone, a leukotriene modifier,
      an inhaled corticosteroid, or switching to use a long-acting beta(2)-adrenoceptor
      agonist. The use of warm-up exercises has been shown to be helpful by using the
      refractory period but is not practical for most children with EIA. A final
      consideration for successful management of EIA in children is that the delivery
      of medication needs to be age-appropriate.

PMID- 11960518
TI  - Hormone replacement therapy falls out of favor with expert committee.

PMID- 11960519
TI  - Changes in anesthesiology practice are explicated.

PMID- 11960520
TI  - Peptides prove predictive for heart failure patients.

PMID- 11960525
TI  - Is one selective serotonin reuptake inhibitor better than another?

PMID- 11960526
TI  - Is one selective serotonin reuptake inhibitor better than another?

PMID- 11960527
TI  - Is one selective serotonin reuptake inhibitor better than another?

PMID- 11960528
TI  - Is one selective serotonin reuptake inhibitor better than another?

PMID- 11960530
TI  - Laparoscopic-assisted surgery for colon cancer.

PMID- 11960531
TI  - Laparoscopic-assisted surgery for colon cancer.

PMID- 11960533
TI  - Withholding of data among academic geneticists.

PMID- 11960535
TI  - Lactobacillus strains and vaginal ecology.

PMID- 11960536
TI  - Thrombolytic therapy vs primary percutaneous coronary intervention for myocardial
      infarction in patients presenting to hospitals without on-site cardiac surgery: a
      randomized controlled trial.
AB  - CONTEXT: Trials comparing primary percutaneous coronary intervention (PCI) and
      thrombolytic therapy for treatment of acute myocardial infarction (MI) suggest
      primary PCI is the superior therapy, although they differ with respect to the
      durability of benefit. Because PCI is often limited to hospitals that have on
      site cardiac surgery programs, most acute MI patients do not have access to this
      therapy. OBJECTIVE: To determine whether treatment of acute MI with primary PCI
      is superior to thrombolytic therapy at hospitals without on-site cardiac surgery
      and, if so, whether superiority is durable. DESIGN: The Atlantic Cardiovascular
      Patient Outcomes Research Team (C-PORT) trial, a prospective, randomized trial
      conducted from July 1996 through December 1999. SETTING: Eleven community
      hospitals in Massachusetts and Maryland without on-site cardiac surgery or extant
      PCI programs. PATIENTS: Four hundred fifty-one thrombolytic-eligible patients
      with acute MI of less than 12 hours' duration associated with ST-segment
      elevation on electrocardiogram. INTERVENTIONS: After a formal primary PCI
      development program was completed at all sites, patients were randomly assigned
      to receive primary PCI (n = 225) or accelerated tissue plasminogen activator
      (bolus dose of 15 mg and an infusion of 0.75 mg/kg for 30 minutes followed by 0.5
      mg/kg for 60 minutes; n = 226). After initiation of assigned treatment, all care
      was determined by treating physicians. MAIN OUTCOME MEASURES: Six-month composite
      incidence of death, recurrent MI, and stroke; median hospital length of stay.
      RESULTS: The incidence of the composite end point was reduced in the primary PCI
      group at 6 weeks (10.7% vs 17.7%; P =.03) and 6 months (12.4% vs 19.9%; P =.03)
      after index MI. Six-month rates for individual outcomes were 6.2% vs 7.1% for
      death (P =.72), 5.3% vs 10.6% for recurrent MI (P =.04), and 2.2% vs 4.0% for
      stroke (P =.28) for primary PCI vs thrombolytic therapy, respectively. Median
      length of stay was also reduced in the primary PCI group (4.5 vs 6.0 days; P
      =.02). CONCLUSIONS: Compared with thrombolytic therapy, treatment of patients
      with primary PCI at hospitals without on-site cardiac surgery is associated with
      better clinical outcomes for 6 months after index MI and a shorter hospital stay.

PMID- 11960537
TI  - Cognitive and motor outcomes of cocaine-exposed infants.
AB  - CONTEXT: Maternal use of cocaine during pregnancy remains a significant public
      health problem, particularly in urban areas of the United States and among women
      of low socioeconomic status. Few longitudinal studies have examined cocaine
      exposed infants, however, and findings are contradictory because of methodologic
      limitations. OBJECTIVE: To assess the effects of prenatal cocaine exposure on
      child developmental outcomes. DESIGN: Longitudinal, prospective, masked,
      comparison birth cohort study with recruitment in 1994-1996. SETTING: Obstetric
      unit of a large US urban teaching hospital. PARTICIPANTS: Four hundred fifteen
      consecutively enrolled infants (218 cocaine-exposed and 197 unexposed) identified
      from a high-risk, low-socioeconomic status, primarily black (80%) population
      screened through clinical interview and urine and meconium samples for drug use.
      The retention rate was 94% at 2 years of age. MAIN OUTCOME MEASURES: The Bayley
      Mental and Motor Scales of Infant Development, assessed at 6.5, 12, and 24 months
      of corrected age. RESULTS: Controlled for confounding variables, cocaine exposure
      had significant effects on cognitive development, accounting for a 6-point
      deficit in Bayley Mental and Motor Scales of Infant Development scores at 2
      years, with cocaine-exposed children twice as likely to have significant delay
      (mental development index <80) (odds ratio, 1.98; 95% confidence interval, 1.21
      3.24; P =.006). For motor outcomes, there were no significant cocaine effects.
      CONCLUSIONS: Cocaine-exposed children had significant cognitive deficits and a
      doubling of the rate of developmental delay during the first 2 years of life.
      Because 2-year outcomes are predictive of later cognitive outcomes, it is
      possible that these children will continue to have learning difficulties at
      school age.

PMID- 11960538
TI  - Improving the quality of hemodialysis treatment: a community-based randomized
      controlled trial to overcome patient-specific barriers.
AB  - CONTEXT: Mortality rates among US hemodialysis patients are the highest in the
      industrialized world at 23% per year. Measures of dialysis dose (Kt/V) correspond
      strongly with survival and are inadequate in one sixth of patients. Inadequate
      dialysis is also associated with increased hospitalizations and high inpatient
      costs. Our previous work identified 3 barriers to adequate hemodialysis: dialysis
      underprescription, catheter use, and shortened treatment time. OBJECTIVE: To
      determine the effect of a tailored intervention on adequacy of hemodialysis.
      DESIGN AND SETTING: Community-based randomized controlled trial with recruitment
      from April 1999 to June 2000 at 29 hemodialysis facilities in northeast Ohio.
      PARTICIPANTS: Forty-four nephrologists and their 169 randomly selected adult
      patients receiving inadequate hemodialysis. INTERVENTION: Nephrologists were
      randomly assigned to an intervention (n = 21) or control (n = 23) group. For
      patients in the intervention group (n = 85), depending on the barrier(s) present,
      a study coordinator gave nephrologists recommendations about optimizing dialysis
      prescriptions, expedited conversion of catheters to surgically created grafts or
      fistulas, and educated patients about the importance of compliance with treatment
      time. Patients in the control group (n = 84) continued to receive usual care.
      MAIN OUTCOME MEASURES: Changes in Kt/V and specific barriers after 6 months.
      RESULTS: At baseline, intervention and control patients had similar Kt/V
      measurements, specific barriers, and demographic and medical characteristics.
      After 6 months, intervention patients had 2-fold larger increases in Kt/V
      compared with control patients (+0.20 vs +0.10; P<.001) and were more likely to
      achieve their facility Kt/V goal (62% vs 42%; P =.01). Intervention patients also
      had nearly 3-fold larger increases in dialysis prescription (+0.16 vs +0.06;
      P<.001) and were 4 times more likely to change from use of catheters to use of
      fistulas/grafts (28% vs 7%; P =.04). CONCLUSIONS: An intervention tailored to
      patient-specific barriers resulted in increased hemodialysis dose. Extending this
      approach to the 33 000 persons in the United States receiving inadequate
      hemodialysis may substantially enhance patient survival, diminish
      hospitalizations, and decrease inpatient expenditures.

PMID- 11960539
TI  - Transfusion-related acute lung injury: report of a clinical look-back
      investigation.
AB  - CONTEXT: Transfusion-related acute lung injury (TRALI) is a syndrome that
      includes dyspnea, hypotension, bilateral pulmonary edema, and fever. TRALI is the
      third leading cause of transfusion-related mortality, but it is probably
      underdiagnosed and underreported. OBJECTIVE: To determine if blood products from
      a frequent plasma donor, whose blood product was implicated in a fatal case of
      TRALI, caused symptoms of TRALI in other recipients of her plasma. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective chart review (conducted from November
      2000 through April 2001) of 50 patients who received blood components within 2
      years (October 1998 through October 2000) from a donor linked to a transfusion
      related fatality. MAIN OUTCOME MEASURE: Occurrence of mild/moderate (dyspnea with
      fever, chills, hypotension, and/or hypoxemia) or severe (acute pulmonary edema or
      need for mechanical ventilation) reaction associated with transfusion. RESULTS:
      Superimposed illness prevented assessment of TRALI in 14 patients. Of the 36
      patient charts that could be reviewed, 7 mild/moderate reactions were reported in
      6 patients (16.7%) and 8 severe reactions were reported in 8 patients (22.2%). Of
      5 patients who received multiple transfusions from the same donor, 2 experienced
      2 reactions: one had 2 mild/moderate reactions and the other had both a
      mild/moderate and a severe reaction. While 5 of the 7 mild/moderate reactions
      were reported to the hospital transfusion service, only 2 of the 8 severe
      reactions were reported. Only 2 reactions (1 mild/moderate and 1 severe) were
      reported to the regional blood collection facility. CONCLUSIONS: TRALI was
      frequently underdiagnosed and underreported in recipients of blood products from
      a donor whose blood products may have caused TRALI in several transfusion
      recipients. Clinical education and awareness of this often-overlooked diagnosis
      are imperative for appropriate prevention and treatment.

PMID- 11960540
TI  - Gastroesophageal reflux, barrett esophagus, and esophageal cancer: scientific
      review.
AB  - CONTEXT: Gastroesophageal reflux disease (GERD) is a risk factor for
      adenocarcinoma of the esophagus, a rare cancer whose incidence is increasing.
      Adenocarcinoma may develop from Barrett esophagus, a metaplastic change of the
      esophageal epithelium from squamous to intestinalized columnar mucosa, which is
      associated with chronic reflux. Some have recommended that patients with chronic
      reflux symptoms undergo upper endoscopy to assess for Barrett esophagus and to
      screen for cancer. OBJECTIVES: To review the evidence linking GERD and Barrett
      esophagus to esophageal adenocarcinoma and to examine the utility of upper
      endoscopy as a screening tool in adenocarcinoma of the esophagus among
      individuals with GERD. DATA SOURCES: A MEDLINE search was performed to identify
      all pertinent English-language reports about GERD, adenocarcinoma, and Barrett
      esophagus from 1968 through 2001. Reports were of randomized controlled clinical
      trials if available, case-control data if trials were unavailable, and cohort
      studies if case-control data were unavailable. Pertinent bibliographies were also
      reviewed to find reports not otherwise identified. STUDY SELECTION AND DATA
      EXTRACTION: Studies were selected by using the search terms gastroesophageal
      reflux, adenocarcinoma, and Barrett's esophagus, with subheadings for
      classification, complications, drug therapy, economics, epidemiology, mortality,
      surgery, and prevention and control. Clinical guidelines for the care of subjects
      with GERD and Barrett esophagus were retrieved and abstracted. DATA SYNTHESIS:
      Cohort studies demonstrate that symptoms of GERD occur monthly in almost 50% of
      US adults and weekly in almost 20%. Three large case-control studies demonstrate
      a positive association between reflux symptoms and risk of adenocarcinoma of the
      esophagus, with more prolonged and severe symptoms accentuating this risk.
      However, because of the low incidence of adenocarcinoma of the esophagus and the
      ubiquity of reflux symptoms, the risk of cancer in any given individual with
      reflux symptoms is low. No randomized trial data are available to demonstrate
      either decreased cancer incidence or increased life expectancy in subjects with
      GERD who undergo screening endoscopy. CONCLUSIONS: Strong evidence supports the
      association of GERD and adenocarcinoma of the esophagus; however, the risk of
      cancer in any given individual with GERD is low. Barrett esophagus appears to be
      a common precursor lesion to this cancer. Given the low absolute risk of cancer
      in those with GERD and the lack of demonstrated efficacy of endoscopic screening,
      insufficient evidence exists to endorse routine endoscopic screening of patients
      with chronic GERD symptoms.

PMID- 11960541
TI  - Gastroesophageal reflux, Barrett esophagus, and esophageal cancer: clinical
      applications.
AB  - Gastroesophageal reflux disease (GERD), a condition commonly encountered in the
      primary care setting, is a risk factor for adenocarcinoma of the esophagus.
      Despite the ubiquity of the complaint, considerable uncertainty exists with
      respect to several basic questions, including when to perform endoscopy in
      patients with chronic reflux symptoms and how to address the cancer risk
      associated with GERD. These clinical vignettes illustrate common clinical
      questions encountered in caring for patients with GERD, especially as they relate
      to the issue of cancer risk. Applying data reviewed in the companion article, we
      propose practical answers to common clinical situations regarding care of
      patients with reflux. We also present an algorithm for treatment of patients with
      chronic GERD symptoms.

PMID- 11960542
TI  - Primary percutaneous coronary intervention for all?

PMID- 11960543
TI  - Cocaine-exposed infants and developmental outcomes: "crack kids" revisited.

PMID- 11960544
TI  - Patient safety efforts should focus on medical injuries.

PMID- 11960545
TI  - Patient safety efforts should focus on medical errors.

PMID- 11960550
TI  - Evidence for the nitration of gamma-tocopherol in vivo: 5-nitro-gamma-tocopherol
      is elevated in the plasma of subjects with coronary heart disease.
AB  - This study investigated the hypothesis that nitration of gamma-tocopherol may be
      an important mechanism for the detoxification of reactive nitrogen oxide species
      in vivo. Using liquid chromatography-tandem MS we have shown that gamma
      tocopherol can be nitrated in vivo to form 5-nitro-gamma-tocopherol and that
      concentrations of this compound are elevated in the plasma of subjects with
      coronary heart disease. In addition, we demonstrate in carotid-artery
      atherosclerotic plaque that nitration of gamma-tocopherol is also evident at
      levels similar to that seen in the plasma of subjects with coronary heart
      disease.

PMID- 11960551
TI  - Cell density related gene expression: SV40 large T antigen levels in immortalized
      astrocyte lines.
AB  - BACKGROUND: Gene expression is affected by population density. Cell density is a
      potent negative regulator of cell cycle time during exponential growth. Here, we
      asked whether SV40 large T antigen (Tag) levels, driven by two different
      promoters, changed in a predictable and regular manner during exponential growth
      in clonal astrocyte cell lines, immortalized and dependent on Tag. RESULTS:
      Expression and cell cycle phase fractions were measured and correlated using flow
      cytometry. T antigen levels did not change or increased during exponential growth
      as a function of the G1 fraction and increasing cell density when Tag was
      transcribed from the Moloney Murine Leukemia virus (MoMuLV) long terminal repeat
      (LTR). When an Rb-binding mutant T antigen transcribed from the LTR was tested,
      levels decreased. When transcribed from the herpes thymidine kinase promoter, Tag
      levels decreased. The directions of change and the rates of change in Tag
      expression were unrelated to the average T antigen levels (i.e., the expression
      potential). CONCLUSIONS: These data show that Tag expression potential in these
      lines varies depending on the vector and clonal variation, but that the observed
      level depends on cell density and cell cycle transit time. The hypothetical
      terms, expression at zero cell density and expression at minimum G1 phase
      fraction, were introduced to simplify measures of expression potential.

PMID- 11960552
TI  - Transforming growth factor-beta1 blocks the enhancement of tumor necrosis factor
      cytotoxicity by hyaluronidase Hyal-2 in L929 fibroblasts.
AB  - BACKGROUND: Functional antagonism between transforming growth factor beta (TGF
      beta) and hyaluronidase has been demonstrated. For example, testicular
      hyaluronidase PH-20 counteracts TGF-beta1-mediated growth inhibition of
      epithelial cells. PH-20 sensitizes various cancer cells to tumor necrosis factor
      (TNF) cytotoxicity by upregulating proapoptotic p53 and WW domain-containing
      oxidoreductase (WOX1). TGF-beta1 blocks PH-20-increased TNF cytotoxicity. In the
      present study, the functional antagonism between TGF-beta1 and lysosomal
      hyaluronidases Hyal-1 and Hyal-2 was examined. RESULTS: Murine L929 fibroblasts
      were engineered to stably express green-fluorescent protein (GFP)-tagged
      hyaluronidase (GFP-Hyal-1 or GFP-Hyal-2) or GFP alone. Compared to control cells,
      Hyal-2-expressing cells had a significantly increased sensitivity to TNF
      cytotoxicity (approximately 60-110% increase), while Hyal-1-expressing cells were
      less sensitive to TNF (approximately 20-90% increase). TNF activated NF-kappaB,
      along with IkappaBalpha degradation, occurred at 20 to 60 min in Hyal-2 cells
      post stimulation, but at the 20 min time point in both control and Hyal-1 cells.
      Hyal-2 cells, but not Hyal-1 and control cells, constitutively expressed WOX1,
      and transiently expressed Hyal-2 enhanced WOX1-mediated cell death. Unlike PH-20,
      Hyal-1 and Hyal-2 did not induce p53 expression. Hyal-2 translocated from the
      lysosome to the mitochondria during staurosporine-mediated apoptosis, suggesting
      that Hyal-2 may damage mitochondria. Finally, Hyal-1 and Hyal-2 blocked TGF-beta1
      enhanced L929 cell growth. In contrast, TGF-beta1 inhibited Hyal-1- and Hyal-2
      increased TNF cytotoxicity in L929 cells by 30-50%. CONCLUSIONS: TGF-beta1 limits
      the ability of Hyal-2 to induce TNF cytotoxicity in L929 cells. Hyal-2-increased
      TNF cytotoxicity in L929 cells appears to be correlated with upregulation of
      WOX1, a prolonged NF-kappaB activation, and Hyal-2 translocation to the
      mitochondria during apoptosis.

PMID- 11960553
TI  - Biofilm formation by nontypeable Haemophilus influenzae: strain variability,
      outer membrane antigen expression and role of pili.
AB  - BACKGROUND: Nontypeable Haemophilus influenzae is an important cause of otitis
      media in children and lower respiratory tract infection in adults with chronic
      obstructive pulmonary disease (COPD). Several lines of evidence suggest that the
      bacterium grows as a biofilm in the human respiratory tract. RESULTS: Fifteen
      clinical isolates from middle ear fluid of children with otitis media and 15
      isolates from sputum of adults with COPD were studied in an in vitro assay of
      biofilm formation. Striking variability among isolates was observed in their
      ability to form biofilms. Analysis of cell envelopes revealed minimal differences
      in banding patterns in polyacrylamide gels, alteration of expression of an
      epitope on lipooligosaccharide, and preservation of expression of selected
      epitopes on outer membrane proteins P2, P5 and P6 in biofilms compared to
      planktonically grown cells. A pilus-deficient variant showed a marked impairment
      in biofilm formation compared to its isogenic parent. CONCLUSIONS: Nontypeable H.
      influenzae forms biofilms in vitro. Clinical isolates show substantial
      variability in their ability to grow as biofilms. Three major outer membrane
      proteins (P2, P5 and P6) are expressed during growth as a biofilm. Expression of
      lipooligosaccharide is altered during growth as a biofilm compared to planktonic
      growth. Pili are important in biofilm formation. As the role of biofilms in human
      infection becomes better defined, characterization of biofilms may be important
      in understanding the pathogenesis of infection and immune response to nontypeable
      H. influenzae in children with otitis media and adults with COPD.

PMID- 11960554
TI  - Cdc5 influences phosphorylation of Net1 and disassembly of the RENT complex.
AB  - BACKGROUND: In S. cerevisiae, the mitotic exit network (MEN) proteins, including
      the Polo-like protein kinase Cdc5 and the protein phosphatase Cdc14, are required
      for exit from mitosis. In pre-anaphase cells, Cdc14 is sequestered to the
      nucleolus by Net1 as a part of the RENT complex. When cells are primed to exit
      mitosis, the RENT complex is disassembled and Cdc14 is released from the
      nucleolus. RESULTS: Here, we show that Cdc5 is necessary to free nucleolar Cdc14
      in late mitosis, that elevated Cdc5 activity provokes ectopic release of Cdc14 in
      pre-anaphase cells, and that the phosphorylation state of Net1 is regulated by
      Cdc5 during anaphase. Furthermore, recombinant Cdc5 and Xenopus Polo-like kinase
      can disassemble the RENT complex in vitro by phosphorylating Net1 and thereby
      reducing its affinity for Cdc14. Surprisingly, although RENT complexes containing
      Net1 mutants (Net1(7m) and Net1(19m') lacking sites phosphorylated by Cdc5 in
      vitro are refractory to disassembly by Polo-like kinases in vitro, net1(7m) and
      net1(19m') cells grow normally and exhibit only minor defects in releasing Cdc14
      during anaphase. However, net1(19m') cells exhibit a synergistic growth defect
      when combined with mutations in CDC5 or DBF2 (another MEN gene). CONCLUSIONS: We
      propose that although Cdc5 potentially disassembles RENT by directly
      phosphorylating Net1, Cdc5 mediates exit from mitosis primarily by
      phosphorylating other targets. Our study suggests that Cdc5/Polo is unusually
      promiscuous and highlights the need to validate Cdc5/Polo in vitro
      phosphorylation sites by direct in vivo mapping experiments.

PMID- 11960555
TI  - Natural antisense RNA inhibits the expression of BCMA, a tumour necrosis factor
      receptor homologue.
AB  - BACKGROUND: BCMA (B-cell maturation) belongs to the tumour necrosis factor
      receptor gene family, and is specifically expressed in mature B lymphocytes.
      Antisense BCMA RNA is produced by transcription from the same locus and has
      typical mRNA features, e.g, polyadenylation, splicing, Kozak consensus sequence
      and an ORF (p12). To investigate the function of antisense BCMA RNA, we expressed
      BCMA in cell lines, in the presence of antisense p12 or a mutant lacking the
      initiation ATG codon (p12-ATG). RESULTS: Overexpression of both p12 and p12-ATG
      antisense BCMA resulted in a large decrease in the amount of BCMA protein
      produced, with no change in BCMA RNA levels, indicating that BCMA expression is
      regulated by antisense BCMA RNA at the translational level. We have also observed
      slight adenosine modifications, suggestive of the activity of a double-stranded
      RNA-specific adenosine deaminase. CONCLUSION: These data suggest that antisense
      BCMA may operate under physiological conditions using similar antisense-mediated
      control mechanisms, to inhibit the expression of the BCMA gene.

PMID- 11960557
TI  - Preoperative Acute Normovolaemic Hemodilution (ANH) in combination with
      Hypotensive Epidural Anaesthesia (HEA) during knee arthroplasty surgery. No
      effect on transfusion rate. A randomized controlled trial [ISRCTN87597684].
AB  - BACKGROUND: Hypotensive epidural anaesthesia (HEA) combines a high epidural
      anaesthesia, performing a sympathetic blockade, with low-dose iv-infusion of
      epinephrine to stabilize circulation in the conscious patient. Mean artery blood
      pressure is reduced to 45-50 mmHg and hereby a reduced blood loss. In this study
      we have combined HEA with preoperative acute normovolaemic hemodilution (ANH) in
      attempt to further reduce the blood loss and need for blood transfusion in total
      knee arthroplasty surgery (TKR). METHODS: Twenty-eight patients scheduled for TKR
      are randomised to ANH or no hemodilution (non-ANH). Both groups are anaesthetized
      with HEA. ANH is established with predonation of 20 % of the total blood volume,
      and replacement with equal volume of HAES 6 %. Blood re-transfusion is completed
      within 6 h. RESULTS: A mean of 877 ml blood was predonated (19.7 % of the total
      blood volume). Blood loss was, except from the intraoperative loss, significantly
      higher in ANH group. The total loss was 1306 mL (ANH) vs. 1026 mL (non-ANH), p <
      0.05. Except from the first hour postoperatively, hematocrit was identical in
      between groups postoperatively. The amount of blood transfusion was identical 386
      ml (ANH) vs. 343 ml (non-ANH) (ns). 50 % went through surgery without receiving
      blood (ANH) vs. 58 % (non-ANH). No renal, neurological or cardiopulmonary
      complications were registered. CONCLUSIONS: These data suggest no benefits in
      combining HEA and ANH in TKR surgery. Probably because of the reduced viscosity
      of the blood after ANH, there is an increased postoperative blood loss. The need
      for homologous blood transfusion was identical.

PMID- 11960556
TI  - Advanced analysis of a cryptochrome mutation's effects on the robustness and
      phase of molecular cycles in isolated peripheral tissues of Drosophila.
AB  - BACKGROUND: Previously, we reported effects of the cry(b) mutation on circadian
      rhythms in period and timeless gene expression within isolated peripheral
      Drosophila tissues. We relied on luciferase activity driven by the respective
      regulatory genomic elements to provide real-time reporting of cycling gene
      expression. Subsequently, we developed a tool kit for the analysis of behavioral
      and molecular cycles. Here, we use these tools to analyze our earlier results as
      well as additional data obtained using the same experimental designs. RESULTS:
      Isolated antennal pairs, heads, bodies, wings and forelegs were evaluated under
      light-dark cycles. In these conditions, the cry(b) mutation significantly
      decreases the number of rhythmic specimens in each case except the wing.
      Moreover, among those specimens with detectable rhythmicity, mutant rhythms are
      significantly weaker than cry+ controls. In addition, cry(b) alters the phase of
      period gene expression in these tissues. Furthermore, peak phase of luciferase
      reported period and timeless expression within cry+ samples is indistinguishable
      in some tissues, yet significantly different in others. We also analyze rhythms
      produced by antennal pairs in constant conditions. CONCLUSIONS: These analyses
      further show that circadian clock mechanisms in Drosophila may vary in a tissue
      specific manner, including how the cry gene regulates circadian gene expression.

PMID- 11960558
TI  - 2, 4-diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR
      signals and ulcer in rat jejunum.
AB  - BACKGROUND: It has been suggested that one aspect of non-steroidal anti
      inflammatory drugs induced intestinal damage is due to either uncoupling of
      mitochondrial oxidative phosphorylation or inhibition of electron transport. We
      investigated the latter possibility using electron paramagnetic resonance
      spectroscopy. RESULTS: Electron paramagnetic studies of NSAIDS on sub
      mitochondrial particles revealed that indomethacin, but not with nabumetone,
      bound to a site near to Complex I and ubiquinone to generate a radical species.
      Normal rats exhibited prominent [3Fe-4S]ox signals (g approximately 2.01) at 20
      K. One hour after indomethacin there was a prominent, intense and broad
      absorption pattern at (g approximately 2.07) suggesting, appearance of radical
      species overlapping [3Fe-4S]ox and was unaffected by pretreatment with 2,4
      diamino -6-hydroxy pyrimidine. At 24 hrs, when macroscopic ulcers were seen,
      there was a new signal due to a nitric oxide radical (NO*). In contrast,
      nabumetone and 2,4 diamino-6-hydroxy pyrimidine pre-treated animals receiving
      indomethacin exhibited electron paramagnetic resonance spectra identical to those
      of controls at 24 hrs and neither was associated with small intestinal ulcers.
      Indomethacin and 2,4 diamino hydroxy pyrimidine pre-treated rats, but not
      nabumetone, had increased intestinal permeability. CONCLUSION: The results
      suggest that the in vivo effects of indomethacin modulate the mitochondrial
      respiratory chain directly at 1 h and 24 h through formation of nitric oxide. NO*
      appears to play an important role in the late pathogenic stages of NSAID
      enteropathy and may be the site for targeted treatment to reduce their toxicity.

PMID- 11960559
TI  - Tetramethylpyrazine attenuates spinal cord ischemic injury due to aortic cross
      clamping in rabbits.
AB  - BACKGROUND: Lower limb paralysis occurs in 11% of patients after surgical
      procedure of thoracic or thoracoabdominal aneurysms and is an unpredictable and
      distressful complication. The aim of this study was to investigate the effects of
      tetramethylpyrazine (TMP), an intravenous drug made from traditional Chinese
      herbs, on the neurologic outcome and histopathology after transient spinal cord
      ischemia in rabbits. METHODS: Forty-five male New Zealand white rabbits were
      anesthetized with isoflurane and spinal cord ischemia was induced for 20 min by
      infrarenal aortic occlusion. Animals were randomly allocated to one of five
      groups (n = 8 each). Group C received no pharmacologic intervention. Group P
      received intravenous infusion of 30 mg x kg(-1) TMP within 30 min before aortic
      occlusion. Group T1, Group T2 and Group T3 received intravenous infusion of 15,
      30 and 60 mg x kg(-1) TMP respectively within 30 min after reperfusion. In the
      sham group (n = 5), the animals underwent the same procedures as the control
      group except infrarental aortic unocclusion. Neurologic status was scored by
      using the Tarlov criteria (in which 4 is normal and 0 is paraplegia) at 4 h, 8 h,
      12 h, 24 h, and 48 h after reperfusion. All animals were sacrificed at 48 h after
      reperfusion and the spinal cords (L5) were removed immediately for
      histopathologic study. RESULTS: All animals in the control group became
      paraplegic. Neurologic status and histopathology (48 h) in the Groups P, T2 and
      T3 were significantly better than those in the control group (P < 0.05). There
      was a strong correlation between the final neurologic scores and the number of
      normal neurons in the anterior spinal cord (r = 0.776, P < 0.01). CONCLUSION:
      Tetramethylpyrazine significantly reduces neurologic injury related to spinal
      cord ischemia and reperfusion after aortic occlusion within a certain range of
      dose.

PMID- 11960560
TI  - Delayed minocycline but not delayed mild hypothermia protects against embolic
      stroke.
AB  - BACKGROUND: Inflammatory reactions occurring in the brain after ischemia may
      contribute to secondary damage. In the present study, effects of minocycline, an
      anti-inflammatory agent, alone or in combination with mild hypothermia on focal
      embolic cerebral ischemia have been examined. METHODS: Focal ischemic injury was
      induced by embolizing a preformed clot into the middle cerebral artery (MCA).
      Infarction volume was measured at 48 h after the injury. Mortality was also
      recorded. RESULTS: Delayed administration of minocycline alone or delayed
      minocycline plus delayed mild hypothermia reduced the infarction volume
      significantly. However, delayed mild hypothermia alone was not protective and
      delayed mild hypothermia in combination with minocycline did not show any
      additive effect. CONCLUSIONS: These results suggest that minocycline is
      beneficial in focal ischemic brain injury, and the lack of the enhanced
      neuroprotection may be due to the brief exposure to hypothermia.

PMID- 11960561
TI  - Adolescent standing postural response to backpack loads: a randomised controlled
      experimental study.
AB  - BACKGROUND: Backpack loads produce changes in standing posture when compared with
      unloaded posture. Although 'poor' unloaded standing posture has been related to
      spinal pain, there is little evidence of whether, and how much, exposure to
      posterior load produces injurious effects on spinal tissue. The objective of this
      study was to describe the effect on adolescent sagittal plane standing posture of
      different loads and positions of a common design of school backpack. The
      underlying study aim was to test the appropriateness of two adult 'rules-of
      thumb'-that for postural efficiency, backpacks should be worn high on the spine,
      and loads should be limited to 10% of body weight. METHOD: A randomised
      controlled experimental study was conducted on 250 adolescents (12-18 years),
      randomly selected from five South Australian metropolitan high schools. Sagittal
      view anatomical points were marked on head, neck, shoulder, hip, thigh, knee and
      ankle. There were nine experimental conditions: combinations of backpack loads
      (3, 5 or 10% of body weight) and positions (backpack centred at T7, T12 or L3).
      Sagittal plane photographs were taken of unloaded standing posture (baseline),
      and standing posture under the experimental conditions. Posture was quantified
      from the x (horizontal) coordinate of each anatomical point under each
      experimental condition. Differences in postural response were described, and
      differences between conditions were determined using Analysis of Variance models.
      RESULTS: Neither age nor gender was a significant factor when comparing postural
      response to backpack loads or conditions. Backpacks positioned at T7 produced the
      largest forward (horizontal) displacement at all the anatomical points. The
      horizontal position of all anatomical points increased linearly with load.
      CONCLUSION: There is evidence refuting the 'rule-of-thumb' to carry the backpack
      high on the back. Typical school backpacks should be positioned with the centre
      at waist or hip level. There is no evidence for the 10% body weight limit.

PMID- 11960562
TI  - Human rights in the biotechnology era 1.
AB  - BACKGOUND: The concept of Human Rights has become the modern civilising standard
      to which all should aspire and indeed attain. DISCUSSION: In an era characterised
      by widening disparities in health and human rights across the world and
      spectacular advances in biotechnology it is necessary to reflect on the extent to
      which human rights considerations are selectively applied for the benefit of the
      most privileged people. Attention is drawn particularly to sub-Saharan Africa as
      a marginalised region at risk of further marginalisation if the power associated
      with the new biotechnology is not used more wisely than power has been used in
      the past. To rectify such deficiencies it is proposed that the moral agenda
      should be broadened and at the very least the concept of rights should be more
      closely integrated with duties SUMMARY: New forms of power being unleashed by
      biotechnology will have to be harnessed and used with greater wisdom than power
      has been used in the past. Widening disparities in the world are unlikely to be
      diminished merely by appealing to human rights. We recommend that a deeper
      understanding is required of the underlying causes of such disparities and that
      the moral discourse should be extended beyond human rights language.

PMID- 11960563
TI  - Abstracts of the 43rd Annual and 2nd Mediterranean Meeting of the Scandinavian
      College of Neuro-Psychopharmacology (SCNP). April 10-13, 2002.

PMID- 11960564
TI  - Predictors of mental distress in early adulthood: a five-year follow-up of 709
      high-school students.
AB  - Mental health risk factors in adolescence were examined as predictors of mental
      distress in early adulthood. A cohort of 709 Finnish adolescents was studied in
      1990 (mean age 16.8) and in 1995. Trait anxiety, defence styles, life events,
      self-esteem and somatic symptoms were evaluated as predictors of high scores in
      the General Health Questionnaire in adulthood. Females (36%) were more likely to
      be distressed than males (23%). High trait anxiety and somatic symptom scores
      among adolescent females, and high immature defence style scores among males
      predicted mental distress. Males with low trait anxiety in adolescence had less
      distress. The results indicate trait anxiety as an important predictor of mental
      distress. Gender differences in other predictors suggest gender differences in
      coping.

PMID- 11960565
TI  - Psychiatric disorders in children with intellectual disability.
AB  - We investigated psychiatric disorders in intellectually disabled children; the
      prevalence rate and types of psychiatric disorders, and the association of
      psychiatric disorders with sex, residence type, level of disability, and epilepsy
      were examined. The population comprised 155 intellectually disabled children.
      Medical information was obtained from case files, which indicated that a
      psychiatric disorder had previously been diagnosed for 11% of patients. A careful
      re-examination of the case files revealed a psychiatric disorder for 33%. The
      criteria of a psychiatric ICD-10 diagnosis were fulfilled by 23%, and a further
      10% had an unspecified mental disorder. The most common diagnoses were pervasive
      developmental disorders and hyperkinetic disorders. The former were less common
      among children with mild intellectual disability. In conclusion, about one-third
      of children with intellectual disability have a psychiatric disorder which needs
      to be taken into account in treatment.

PMID- 11960566
TI  - False claims of victimization: a historical illustration of a contemporary
      problem.
AB  - In this article, a false claim of victimization made by a man in his late 20s
      during a 17th-century outbreak of mass allegations of Satanic abuse is described
      and discussed in relation to contemporary issues with relevance to psychiatry and
      applied mental health.

PMID- 11960567
TI  - Mental and personality disorders as well as personality traits in a Swedish male
      criminal population.
AB  - The study describes personality traits and the presence of personality disorders
      and mental disorders in a consecutive series of 130 male prisoners in Swedish
      jails sentenced for serious criminality. The investigation included a psychiatric
      examination by means of the Structured Clinical Interview (SCID) as well as
      information taken from criminal records. Personality assessments were made by
      means of self-report questionnaires, the Karolinska Scales of Personality (KSP)
      and the DSM-IV and ICD-10 Personality Disorder Questionnaire (DIP-Q). The most
      common mental disorders were alcohol and drug abuse/dependence, which were
      present in 55% of the subjects. Personality disorders, too, were common, being
      present in 56% of the subjects. In the KSP, high scores were found in scales
      related to impulsiveness, sensation-seeking, nervous tension and distress,
      cognitive-social anxiety, hostility and aggression. Very low scores were found in
      the Socialization scale, reflecting a high degree of psychopathy-related
      personality traits. Despite the high morbidity, the global level of functioning
      was unexpectedly high, 66 according to GAF. The male prisoners sentenced for
      heavy criminality had a high degree of both mental disorders and personality
      disorders. Furthermore, psychopathy-related personality traits were common.

PMID- 11960568
TI  - Block-training in group psychotherapy in the Baltic States: Experiences from
      three years of training.
AB  - Since March 1995, the Institute of Group Analysis, Norway has been responsible
      for a block-training programme in group psychotherapy in Vilnius, Lithuania.
      Training takes place in English during five weekends per year, with participants
      from all three Baltic countries. There are three levels: one year basic course,
      two years advanced course and two years qualifying course. Elements in the
      training are self-experience in small and large groups, supervision and theory
      discussions. The plan is to educate local staff, who can then train colleagues on
      an independent basis. Evaluations show a high degree of satisfaction with the
      different elements of the course, and an initial honeymoon attitude has given way
      to a more realistic realization of what is required of a personal and
      professional commitment. Experiences from the first three years of training are
      presented.

PMID- 11960569
TI  - Non-compliance in community psychiatry: failed appointments in the referral
      system to psychiatric outpatient treatment.
AB  - Knowledge about the drop-out pattern of psychiatric patients in the referral
      phase for outpatient treatment is limited. The aim of the present study was to
      investigate the importance of selected psychiatric, demographic and
      administrative parameters in this matter. In a newly opened community psychiatric
      unit with an open referral system, available relevant data concerning the
      referred patients were gathered over a 6-month period. Of the 137 patients
      included in the study, 32% did not show up for their first appointment. On making
      further attempts to contact the patients, the drop-out frequency dropped to 16%,
      demonstrating that it is worthwhile offering new appointments to the patients who
      do not show up. There was no demonstrable relation between the time the patients
      had waited for the first appointment with a psychiatrist and the drop-out
      frequency. For patients who had been referred with a diagnosis of psychosis (F 20
      29, WHO criteria), or addiction, or had been previously admitted to psychiatric
      hospital, there was a significant increase in the drop-out rate.

PMID- 11960570
TI  - How should a scientific team be effectively formed and managed.
AB  - In the research process, hypotheses, observations and raw data are systematically
      transformed into new knowledge and scientific rules. People and human input are
      essential features of the research; the intellectual process performed by the
      individual scientists and their team. Unplanned administration and human
      conflicts are the major causes of unsuccessful research. In this article, some
      essential organizational and psychological aspects of the scientific team are
      described and discussed. In addition, practical guidelines on forming, working
      and managing a research team are presented.

PMID- 11960571
TI  - Closing the gaps in genetics legislation and policy: a report by the new york
      state task force on life and the law.
AB  - The New York State Task Force on Life and the Law, a state bioethical policy
      commission, recently completed a project addressing the ethical, legal, and
      social concerns surrounding the predictive uses of genetic testing. Its report,
      Genetic Testing and Screening in the Age of Genomic Medicine, makes legislative,
      public policy, and practice recommendations on a host of issues. As part of this
      project, the Task Force reviewed the current policy and legislative landscapes
      related to confidentiality protections for genetic information and the use of
      genetic information by insurers. It also assessed requirements for informed
      consent to clinical genetic testing and for the use of clinical samples for
      genetics research. The Task Force considered gaps and unintended consequences of
      relevant genetic testing legislation and assessed its flexibility to address new
      uses of genetic testing, such as pharmacogenetic testing, and new ways of
      offering tests, such as multiplex testing panels. The Task Force also considered
      the relevance of the pleiotropic characteristic of genes for issues of informed
      consent to genetic testing and the confidentiality of genetic information. The
      Task Force's recommendations, presented here, seek to promote the appropriate
      uses of clinical genetic testing and research while preventing potential harms.

PMID- 11960572
TI  - Detection of sequence variations in the adenomatous polyposis coli (APC) gene
      using denaturing high-performance liquid chromatography.
AB  - We have evaluated the usefulness of denaturing high performance liquid
      chromatography (dHPLC) for scanning the adenomatous polyposis coli (APC) gene for
      point mutations, small deletions, and insertions. Our assay consists of 28 sets
      of primers to amplify the 15 exons of the APC gene. All PCR reactions were
      amplified simultaneously using the same reaction conditions in a 96-well format
      and then analyzed by dHPLC, using empirically determined optimum temperatures for
      partial fragment denaturation. Previously studied DNA specimens from 47 familial
      adenomatous polyposis (FAP) patients were analyzed by dHPLC and all mutations
      were correctly identified and confirmed by sequence analysis. This approach
      identified a single-base substitution in exon 6 and a 2-bp insertion in exon 15
      that initially had not been detected by single-strand conformational polymorphism
      (SSCP) analysis. A novel mutation in exon 15 of the APC gene, 2065delG (codon
      689) that had previously been undetected by the protein truncation test (PTT) was
      also identified by dHPLC. We present our validation studies of dHPLC technology
      for APC gene analysis in terms of sensitivity and specificity and compare it to
      current standard scanning technologies including PTT, SSCP, and conformational
      sensitive gel electrophoresis (CSGE).

PMID- 11960573
TI  - Factor V Leiden mutation screened by PCR and detected with lanthanide-labeled
      probes.
AB  - The Factor V Leiden mutation is an important human polymorphism, responsible for
      increased risk of venous thrombosis in heterozygotes as well as homozygotes.
      Therefore, screening is a useful possibility, and many detection systems have
      been described for PCR products. We have developed a simplified and robust assay
      using oligonucleotide probes for normal and mutant sequences, labeled with
      europium and samarium, respectively, and measured by time-resolved fluorescence.
      Populations consisting of 233 Welsh and 148 Irish subjects were examined by both
      restriction fragment length polymorphism (RFLP) analysis and our assay. The
      allele frequency was 14/466 in the Welsh and 5/296 in the Irish population, in
      line with other surveys of European populations. Results were not obtained in
      2/381 samples by RFLP, compared with 1/381 with our method. We conclude that our
      method represents an improved system capable of considerable throughput at
      reasonable cost.

PMID- 11960574
TI  - HFE genotype frequencies in consecutive reference laboratory specimens:
      comparisons among referral sources and association with initial diagnosis.
AB  - We quantified HFE genotype frequencies in specimens submitted by physicians
      grouped by specialty and determined associations of genotypes with initial
      diagnosis based on phenotyping in patients evaluated at an iron disorders center.
      Of 526 specimens (519 from Alabama), these "typical" hemochromatosis-associated
      genotypes were detected: 85 C282Y/C282Y, 50 C282Y/H63D, and 27 H63D/H63D.
      Respective frequencies of C282Y/C282Y in specimens from an iron disorders center
      (n = 156), gastroenterologists (n = 147), hematologists/medical oncologists (n =
      85), liver transplant surgeons (n = 11), endocrinologists and rheumatologists (n
      = 9), and "other sources" (n = 7) were greater (p < 0.05) than in population
      controls. In 44 patients from an iron disorders center initially diagnosed as
      "presumed hemochromatosis," 27 (61.4%) had C282Y/C282Y, 10 (22.7%) had
      C282Y/H63D, and 3 (6.8%) had H63D/H63D. C282Y/C282Y was not detected in 48
      patients with "abnormality probably not an iron overload disorder." A total of
      20.5% of 44 family members of patients had "typical" hemochromatosis-associated
      HFE genotypes (7.0% controls; p = 0.02). We conclude that most physicians who
      submitted specimens identify patients by phenotyping who have greater frequencies
      of "typical" hemochromatosis-associated HFE genotypes than controls, and that HFE
      mutation testing is useful in detecting hemochromatosis in family members of
      persons with hemochromatosis or iron overload.

PMID- 11960575
TI  - Web-site-based recruitment for research studies on abdominal aortic and
      intracranial aneurysms.
AB  - Our current understanding on the pathogenesis of abdominal aortic and
      intracranial aneurysms is limited, but genetic and environmental factors as well
      as their interactions are likely to play important roles in the development and
      rupture of aneurysms. To identify genetic factors contributing to these diseases,
      we are carrying out genome-wide screening studies, which require a large number
      of patients and family members. Current methods of finding patients who qualify
      for genetic studies are, however, often costly and ineffective. To improve
      patient recruitment, a Web site was developed (cmmg.biosci.wayne.edu/ags). The
      site gives general information about our study, solicits participation into the
      study, and provides links to relevant medical and educational sites. During the
      time period of July, 1999, to December, 2000, the site received 5, 108 visits (13
      visits/day). Approximately 20 research study applications are received each
      month. A total of 49% (57/117) of the individuals responding to the aortic
      aneurysm and 63% (84/134) responding to the intracranial aneurysm study report at
      least two affected blood relatives in the family and, therefore, qualify for our
      genetic studies. In conclusion, Web-based patient recruitment is successful and
      provides an improved success rate due to the fact that the responders are more
      motivated to participate in research studies.

PMID- 11960576
TI  - A primer for predicting risk of disease in HFE-linked hemochromatosis.
AB  - Since the discovery of the hemochromatosis gene (HFE) in 1996, there has been
      increasing interest in diagnostic testing for the C282Y and H63D mutations. The
      high frequency of these two alleles and their incomplete penetrance in
      homozygotes and compound heterozygotes make genetic counseling for
      hemochromatosis different from some other autosomal recessive conditions in that
      parents and children may also be at risk for iron overload, while homozygotes may
      remain asymptomatic. We provide a guideline for genetic counseling in HFE-linked
      hemochromatosis based on the genetic probability of inheriting HFE mutations and
      known information about expression of iron overload in various HFE genotypes.
      Genetic probabilities were based on allele frequencies derived from large
      population studies and Hardy-Weinberg equilibrium estimates. Expression of iron
      overload in those of various genotypes was based on available estimates of serum
      ferritin from population screening studies. Estimates for the likelihood of
      clinical iron overload requiring follow-up screening or treatment are provided by
      gender and genotype. The probability of inheriting HFE mutations and developing
      iron overload can be estimated in family members of a proband with HFE mutations.
      Many C282Y homozygotes will not have clinical iron overload. The risk is highest
      in men and their C282Y homozygous brothers and significantly lower in homozygous
      women. Iron overload is uncommon in compound heterozygotes and H63D homozygotes.

PMID- 11960577
TI  - Acceptance of neonatal genetic screening for hereditary hemochromatosis by
      informed parents.
AB  - The aim of this study was to assess attitudes to neonatal genetic screening for
      hereditary hemochromatosis. A total of 135 consecutive, pregnant women and their
      partners attending a hospital antenatal clinic in the Australian Capital
      Territory were given detailed written and verbal information about potential
      risks and benefits of neonatal genetic screening. Issues such as uncertainty of
      disease expression, confidentiality, genetic discrimination, and storage of
      genetic data were addressed. Attitudes were assessed by interview and
      questionnaire. There was a high level of acceptance for neonatal genetic
      screening in general (99%) and for hemochromatosis in particular (91.5%). There
      was no association of prior knowledge of hemochromatosis, family history of
      hemochromatosis, ethnicity, age, education, or occupation class with
      nonacceptance. Of the subjects, 39.5% reported feeling "a little anxious" about
      the prospect of screening their infants, although only 5.4% reported feeling
      "very anxious." Reasons given for nonacceptance of screening included inability
      of the child to give informed consent, insufficient evidence that diagnosis of
      hemochromatosis in childhood is beneficial, risk of discrimination on genetic
      grounds, lack of agreement between partners, and privacy issues. These data
      suggest that an Australian neonatal genetic screening program for hemochromatosis
      is likely to be accepted by this and similar groups of subjects, but there should
      be an opportunity for parents who object to screening to opt out of any such
      program.

PMID- 11960578
TI  - Mutation analysis in Rett syndrome.
AB  - Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by
      mutations in the MECP2 gene. Mutations have been demonstrated in more than 80% of
      females with typical features of Rett syndrome. We identified mutations in the
      MECP2 gene and documented the clinical manifestations in 65 Rett syndrome
      patients to characterize the genotype-phenotype spectrum. Bidirectional
      sequencing of the entire MECP2 coding region was performed. We diagnosed 65
      patients with MECP2 mutations. Of these, 15 mutations had been reported
      previously and 13 are novel. Two patients have multiple deletions within the
      MECP2 gene. Eight common mutations were found in 43 of 65 patients (66.15%). The
      majority of patients with identified mutations have the classic Rett phenotype,
      and several had atypical phenotypes. MECP2 analysis identified mutations in
      almost all cases of typical Rett syndrome, as well as in some with atypical
      phenotypes. Eleven (20.4%) of the 54 patients with defined mutations and in whom
      phenotypic data were obtained did not develop acquired microcephaly. Hence,
      microcephaly at birth or absence of acquired microcephaly does not obviate the
      need for MECP2 analysis. We have initiated cascade testing starting with PCR
      analysis for common mutations followed by sequencing, when necessary. Analysis of
      common mutations before sequencing the entire gene is anticipated to be the most
      efficacious strategy to identify Rett syndrome gene mutations.

PMID- 11960579
TI  - Detection of severe nondeletional alpha-thalassemia mutations using a single-tube
      multiplex ARMS assay.
AB  - Alpha-thalassemia is a common hereditary anemia due to decreased or absent
      synthesis of alpha-globin chains. The most common causes of alpha-thalassemia are
      deletions that remove one or both functional alpha-globin genes, with a small
      proportion of cases involving nondeletional mutations of the alpha2- or alpha1
      globin genes. Herein, we describe a single-tube multiplex amplification
      refractory mutation system (ARMS) assay for rapid detection of six of the most
      common and severe nondeletional alpha-thalassemia mutations. These alleles are
      found predominantly among southeast Asian populations, and are associated with
      the most severe forms of hemoglobin (Hb) H disease or Hb H hydrops fetalis.

PMID- 11960580
TI  - Genetic analysis of Brugada syndrome in Israel: two novel mutations and possible
      genetic heterogeneity.
AB  - Idiopathic ventricular fibrillation in patients with an electrocardiogram (ECG)
      pattern of right bundle branch block and ST-segment elevation in leads V1 to V3
      (now frequently called Brugada syndrome) is associated with a high incidence of
      syncopal episodes or sudden death. The disease is inherited as an autosomal
      dominant trait. Mutations in SCN5A, a cardiac sodium channel gene, have been
      recently associated with Brugada syndrome. We have analyzed 7 patients from
      Israel affected with Brugada syndrome. The families of these patients are
      characterized by a small number of symptomatic members. Sequencing analysis of
      SCN5A revealed two novel mutations, G35S and R104Q, in two Brugada patients, and
      a possible R34C polymorphism in two unrelated controls. No mutations were
      detected in 5 other patients, suggesting genetic heterogeneity. Low penetrance is
      probably the cause for the small number of symptomatic members in the two
      families positive for the SCN5A mutations.

PMID- 11960581
TI  - Two families with blepharophimosis/ptosis/epicanthus inversus syndrome have
      mutations in the putative forkhead transcription factor FOXL2.
AB  - Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES) is an autosomal
      dominant disorder that is characterized by distinctive eyelid abnormalities. Two
      clinical subtypes have been described in which type I, but not type II, is
      associated with premature ovarian failure. Both types of BPES are linked to 3q22
      23, and the gene has recently been identified as the putative forkhead
      transcription factor FOXL2. We report mutation screening of FOXL2 in two families
      with this condition. The two mutations detected were frameshift mutations
      resulting from a small insertion or duplication within the gene. Both mutations
      would result in the production of novel carboxyl terminii, one terminating the
      predicted protein earlier than the wild type, and the other giving rise to a
      larger protein product, assuming these proteins or their mRNA were not degraded.
      Based on the present data, this would suggest that the first family should be
      type I and the second, type II. Although there is evidence of infertility in the
      first family, all 3 females in the youngest generation have normal pelvic
      ultrasound and hormone levels, suggesting that the divide between types I and II
      may not be as distinct as has been suggested.

PMID- 11960582
TI  - Evaluation of dHPLC for CX26 mutation screening in patients from southern France
      with sensorineural deafness.
AB  - The GJB2 gene (or CX26 for connexin 26) is one of the major genes causing
      nonsyndromic sensorineural hearing loss (NSSNHL). More than 50 sequence
      variations have been identified as polymorphisms or associated with autosomal or
      recessive forms of deafness. Though a major mutation, 35delG, is easily
      detectable by PCR digest; it is often present in the compound heterozygous state
      in our population in trans with recurrent, but less frequent, mutations. The CX26
      gene is composed of a single coding exon that facilitates sequencing strategies.
      However, for mutation screening purposes, it is necessary to use high-throughput
      and cost-effective genotyping methods. Therefore, we have assessed denaturing
      high-performance liquid chromatography (dHPLC) in patients with known mutations
      in the CX26 gene. We conclude that dHPLC analysis is suitable for rapid and
      reliable scanning of the gene in deaf patients.

PMID- 11960583
TI  - Chromosome 8.

PMID- 11960584
TI  - The role of infection in the genesis and complications of atherosclerosis.

PMID- 11960586
TI  - Is heart failure with preserved systolic function an overlooked enigma?
AB  - Heart failure with preserved systolic function, or diastolic heart failure,
      represents the neglected other half of the pandemic of heart failure. Unlike
      previously held beliefs, diastolic heart failure carries with it the same
      connotation of morbidity and mortality as systolic heart failure, particularly in
      the elderly. Due to lack of standards in application of the diagnosis of
      diastolic heart failure, studies are difficult to interpret due to heterogeneity
      in the clinical criteria applied to the patient enrollment. It is imperative that
      preventive efforts be implemented in high-risk groups, and screening measures
      with newer biomarkers be considered for identifying underlying structural heart
      disease in order to employ preventive therapy early in the course of illness. No
      evidence-based therapeutic strategy to reduce morbidity and mortality has been
      established, even after the diagnosis of diastolic heart failure is manifest.
      Current therapy targets lusitropic abnormalities in the realm of impaired
      relaxation, abnormal diastolic compliance, avoidance of tachycardia, and
      restoration of atrial booster pump function. Outcomes-based placebo-controlled
      clinical trials are currently underway to define appropriate therapeutic
      strategies in diastolic heart failure.

PMID- 11960587
TI  - Prevention of heart failure.
AB  - In light of the increasing prevalence, morbidity, and mortality of heart failure,
      preventative strategies are urgently needed. Risk factors include coronary artery
      disease, renal insufficiency, diabetes, and smoking. Essential strategies for
      prevention of heart failure are modification of risk factors for its development,
      and detection and treatment of asymptomatic left ventricular dysfunction (ALVD).
      In patients with ALVD, angiotensin-converting enzyme (ACE) inhibitor and beta
      blocker therapy can prevent progression to symptomatic heart failure. Additional
      recently identified preventative strategies include ACE inhibitor therapy for all
      coronary artery disease and diabetic patients, clopidogrel therapy in acute
      coronary syndromes, and avoidance of calcium channel blockers and alpha-blockers
      as first-line antihypertensive therapy.

PMID- 11960588
TI  - The role of inflammation in the pathogenesis of heart failure.
AB  - Heart failure is not a simple defect in the pumping function of cardiac muscle,
      but rather a complex systemic inflammatory disease affecting many organ systems.
      Recognition of this fact has led to new therapeutic interventions such as
      angiotensin-converting enzyme inhibitors and beta-blockers, which have a
      significant impact on the quality of life and survival of patients with heart
      failure. During the course of heart failure, the steps involved in the activation
      of inflammation are now better understood. As a result, new therapies will
      develop that block, modify, or prevent these inflammatory changes, and supplement
      our armamentarium for providing better and longer lives for patients.

PMID- 11960589
TI  - The role of endothelin in the pathogenesis of heart failure.
AB  - In fewer than than 15 years since its discovery, endothelin is now recognized as
      playing a central role in the pathogenesis of chronic heart failure. This review
      examines the signaling pathways and mechanism of action of endothelin in relation
      to the studies that have elucidated this role. Early investigations observed that
      the endothelin system is markedly upregulated in heart failure, whereas others
      demonstrated that endothelin is the most potent vasoconstrictor. However, it has
      multiple other actions, including mediating pathologic hypertrophy and fibrosis
      of both ventricular and vascular tissues, acting as a proarrhythmic, and
      potentiating the effects of other neurohormones. Endothelin receptor antagonists
      were developed to investigate the hypothesis that these adverse effects could be
      prevented and experimental studies showed promise in this regard. Clinical
      studies to date have not fulfilled this promise. Further analysis of these trials
      will hopefully provide insight into these disparate findings and guidance for
      future investigations.

PMID- 11960591
TI  - The role of race in heart failure therapy.
AB  - Heart failure in blacks is a unique malady characterized by a different natural
      history, more worrisome prognosis, and potential variances in the response to
      current medical therapy for heart failure. The overwhelming burden of
      hypertension as a putative cause of left ventricular dysfunction identifies this
      illness. Although differences in the response to medical therapy have been
      described, angiotensin-converting enzyme inhibitors and beta-blockers remain the
      most appropriate therapy. Certain genetic polymorphisms may exist that explain
      the observed differences.

PMID- 11960592
TI  - Hypertrophic cardiomyopathy: management issues in the new millennium.
AB  - Hypertrophic cardiomyopathy is an inherited cardiac disorder. Sudden cardiac
      death frequently occurs in otherwise healthy individuals, and accounts for nearly
      35% of all sudden deaths within this age group. Although symptoms occur commonly,
      they often go unreported. Despite this, a degree of functional limitation is
      often seen on objective assessment. Management of hypertrophic cardiomyopathy is
      aimed at relieving symptoms, identifying and treating those individuals at
      increased risk of sudden death, and screening family members.

PMID- 11960593
TI  - New surgical treatments for heart failure.
AB  - Medical therapy for heart failure is quickly advancing, but long-term survival
      unfortunately remains poor. New surgical techniques seek to halt and reverse the
      progression of heart failure. Positron emission tomography has refined patient
      selection techniques for coronary artery bypass grafting in the failing heart.
      Left ventricular (LV) remodeling surgery and new devices change the shape of the
      LV and decrease LV wall stress. Passive restraint devices improve systolic
      function by preventing ventricular dilatation. LV assist devices have proven to
      be effective and provide a significantly higher 1-year survival rate when
      compared with maximal medical therapy. New ideas and devices are defining a new
      role for surgical treatment of the aging population of the United States and may
      provide the answer to long-term management of heart failure.

PMID- 11960594
TI  - Current status and future expectations for multisite pacing in heart failure.
AB  - The number of patients with congestive heart failure (CHF) has achieved
      astonishing proportions. It is a debilitating and usually lethal condition, aside
      from being responsible for an enormous proportion of health care expenditures.
      Advances in medical therapy have not been sufficient to significantly improve
      prognosis, and heart transplantation can only benefit a minority of patients.
      Biventricular pacing has emerged as a promising form of therapy for patients with
      severe, medical refractory CHF with ventricular conduction defects. However,
      there are many technical issues to be solved, and better methods of selecting
      patients who respond favorably to this form of therapy are yet to be developed.
      This article reviews the rationale, delivery modes, and available data supporting
      multisite cardiac pacing as an alternative form of therapy for the failing heart.

PMID- 11960595
TI  - Chemokines as novel therapeutic targets in inflammatory diseases.
AB  - Chemokines and their receptors are a large family of inflammatory molecules
      responsible for a number of biological functions, including the accumulation of
      leukocytes at tissue sites. Over the past 10 years, a number of studies have
      indicated a role for chemokines and chemokine receptors in the pathophysiology of
      several inflammatory diseases, examples of which are multiple sclerosis,
      atherosclerosis, rheumatoid arthritis, and gastrointestinal diseases including
      hepatic disease. For this reason, it is not surprising that modulation of their
      pharmacology could be a prime target for drug discovery. This commentary provides
      a brief synopsis of our current knowledge of the role of chemokines and their
      receptors in the inflammatory process, and highlights the pros and possibly cons
      of chemokine and chemokine receptor antagonism in the therapeutic approach to
      several inflammatory diseases.

PMID- 11960596
TI  - Selective inhibition of STAT3 phosphorylation by sodium salicylate in cardiac
      fibroblasts.
AB  - The effects of salicylate on the phosphorylation and nuclear translocation of
      signal transducers and activators of transcription (STATs) induced by interferon
      gamma (IFN-gamma) were studied in rat cardiac fibroblasts as a possible model for
      the anti-inflammatory effects of salicylate on this signaling pathway. Salicylate
      inhibited the tyrosine phosphorylation of both STAT1 and STAT3, but had a more
      pronounced effect on STAT3 activation. Salicylate pretreatment prevented both the
      nuclear translocation and the DNA-binding activity of STAT1 and STAT3, assessed
      by immunoblotting and gel shift assays, respectively. In addition to causing
      phosphorylation at tyrosine residues, IFN-gamma also phosphorylated STAT3 and
      STAT1 at serine 727. Salicylate attenuated both tyrosine and serine
      phosphorylations of STAT3, and also suppressed extracellular signal-regulated
      kinase (ERK) activation, implicating the effect of salicylate on ERK as a
      possible mechanism for attenuating STAT3 activation. The possibility that
      salicylate might affect signaling cascades by altering the redox state of the
      cells was examined, and its effects differed from those of other reducing agents.
      Salicylate did attenuate the effects of hydrogen peroxide on STAT
      phosphorylation, consistent with a mechanism involving an interaction between
      salicylate and reactive oxygen species within the cell.

PMID- 11960597
TI  - In vitro pharmacokinetics and pharmacodynamics of 1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU).
AB  - The relationship between treatment efficacy and the pharmacokinetics (PK) and
      pharmacodynamics (PD) of anticancer drugs is poorly defined. 1,3-Bis(2
      chloroethyl)-1-nitrosourea (BCNU) is an alkylating agent used in the treatment of
      brain and other forms of cancer. It is postulated that BCNU kills cells by
      forming DNA interstrand cross-links. The present study was undertaken to
      characterize the PK and PD of BCNU in mouse L1210 cells. L1210 cells were exposed
      to BCNU (0-160 microM) and analyzed for intracellular BCNU concentrations, DNA
      interstrand cross-links, cell cycle phase, and cytotoxicity. The half-life of
      BCNU in cells was approximately 40 min. The maximum reduction of mitochondrial
      enzyme activity (maximum cell death) achieved within 24 hr after exposure to BCNU
      was concentration-dependent and could be described by a Hill equation. At lower
      concentrations, the area under the DNA interstrand cross-link-time curve linearly
      correlated with the maximum cell death and the area under the BCNU concentration
      time curve. BCNU induced cell accumulation in the G(2)/M phase of the cell cycle,
      which continued even after apparent completion of cross-link repair. Loss of
      membrane permeability was minimal (approximately 2%) during the first 24 hr.
      Thereafter, cells died exponentially over the next 9 days, primarily by necrosis.
      In conclusion, while cytotoxicity was concentration-dependent, an indirect
      relationship was found among the time-course of BCNU concentrations, DNA
      interstrand cross-links, and cell death. Because of the disparity between the
      time-scale of PK and PD, focusing only on the early events may provide limited
      information about the process of anticancer drug-induced cell death.

PMID- 11960598
TI  - Biochemical changes associated with a multidrug-resistant phenotype of a human
      glioma cell line with temozolomide-acquired resistance.
AB  - Temozolomide (TMZ) is a newly approved alkylating agent for the treatment of
      malignant gliomas. To investigate resistance mechanisms in a multidrug
      therapeutic approach, a TMZ-resistant human glioma cell line, SF188/TR, was
      established by stepwise exposure of human SF188 parental cells to TMZ for
      approximately 6 months. SF188/TR showed 6-fold resistance to TMZ and cross
      resistance to a broad spectrum of other anticancer agents that included 3-5-fold
      resistance to melphalan (MEL), gemcitabine (GEM), paclitaxel (PAC), methotrexate
      (MTX), and doxorubicin (DOX), and 1.6-2-fold resistance to cisplatin (CDDP) and
      topotecan (TPT). Alkylguanine alkyltransferase (AGT) activity was increased
      significantly in the resistant cell line compared with the parental cell line
      (P<0.05), whereas no significant differences occurred in the cellular uptake of
      TMZ and PAC between resistant and parental cells. Depletion of AGT by O(6)
      benzylguanine significantly increased the cytotoxicity of TMZ in both the
      sensitive and resistant cell lines, but did not influence the cytotoxicity of the
      other drugs tested. Treatment with TMZ caused SF188 cells to accumulate in S
      phase, whereas SF188/TR cells were unaffected. Expression of Bcl-2 family members
      in SF188/TR cells compared with SF188 cells indicated that the pro-apoptotic
      proteins (i.e. Bad, Bax, Bcl-X(S)) were reduced 2-4-fold in the resistant cell
      line, whereas the anti-apoptotic proteins Bcl-2 and Bcl-X(L) were expressed at
      similar levels in both cell lines. In conclusion, the mechanism of resistance of
      SF188/TR cells to TMZ involved increased activity of AGT, a primary resistance
      mechanism, whereas the broad cross-resistance pattern to other anticancer drugs
      was due to a common secondary resistance mechanism related to alterations in the
      relative expression of the pro-apoptotic and anti-apoptotic proteins.

PMID- 11960599
TI  - Chronic ethanol administration decreases the ligand binding properties and the
      cellular content of the mannose 6-phosphate/insulin-like growth factor II
      receptor in rat hepatocytes.
AB  - We have shown previously that chronic ethanol administration impairs the
      maturation of lysosomal enzymes in rat hepatocytes. The mannose 6
      phosphate/insulin-like growth factor II receptor (M6P/IGF-IIR) is a protein that
      facilitates the transport of lysosomal enzymes into the lysosome. Therefore, we
      examined whether ethanol consumption altered the ligand binding properties and
      the cellular content of M6P/IGF-IIR. Rats were pair-fed liquid diets containing
      either ethanol (36% of calories) or isocaloric maltose-dextrin for either 1 week
      or 5-7 weeks. Hepatocytes prepared from these animals were examined for receptor
      ligand binding and receptor content. One week of ethanol feeding had no
      significant effect on ligand [radioiodinated pentamannose phosphate conjugated to
      bovine serum albumin ((125)I-PMP-BSA)] binding to hepatocytes, but cells from
      rats fed ethanol for 5-7 weeks bound less (125)I-PMP-BSA than pair-fed controls.
      Scatchard plot analysis revealed that the number of (125)I-PMP-BSA binding sites
      in hepatocytes from ethanol-fed rats was 49% lower than that of controls. (125)I
      PMP-BSA binding by perivenular (PV) and periportal (PP) hepatocytes from ethanol
      fed rats was, respectively, 40 and 48% lower than their controls, but there was
      no significant difference between these two types of hepatocytes. Ligand blot
      analysis using (125)I-insulin-like growth factor II ((125)I-IGF-II) also showed
      that the receptor in lysates of hepatocytes from ethanol-fed rats bound 26-27%
      less ligand than controls. Similarly, immunoblot analysis of cell lysates from
      ethanol-fed rats revealed 62% lower levels of immunoreactive M6P/IGF-IIR than
      controls. Feeding rats a low carbohydrate-ethanol diet did not exacerbate the
      reduction in M6P/IGF-IIR-ligand binding nor did it reduce the levels of
      immunoreactive receptor. Our findings indicate that chronic ethanol consumption
      lowers M6P/IGF-IIR activity and content in hepatocytes. This reduction may
      account, in part, for the impaired processing and delivery of acid hydrolases to
      lysosomes previously observed in ethanol-fed rats.

PMID- 11960600
TI  - Sensitization of human neutrophil defense activities through activation of
      platelet-activating factor receptors by ginkgolide B, a bioactive component of
      the Ginkgo biloba extract EGB 761.
AB  - Ginkgolide B (GKB, BN 52021) was described as a platelet-activating factor (Paf)
      receptor antagonist. However, it is not known whether all GKB biological effects
      are mediated through Paf receptor antagonism only. To gain insight into the drug
      mode of action, we investigated here the effects of GKB per se on functional and
      signaling activities in human polymorphonuclear leukocytes (PMN). Treatment of
      PMN with GKB (0.5-12 microM) stimulates a rapid and weak production of reactive
      oxygen species determined by chemiluminescence. ROS production required the
      activation of protein kinase C (PKC), tyrosine kinases and p38 mitogen-activated
      protein kinase as indicated by inhibitory effects of, respectively, GF 109203X
      (IC(50) of 0.5 microM), genistein (IC(50) of 0.5 microM) and SB 203580 (IC(50) of
      0.2 microM) or SB 202190 (IC(50) of 1.1 microM). GKB stimulated a Pertussis toxin
      sensitive PLD activity assessed by the formation of tritiated phosphatidic acid
      and choline. By contrast, GKB did prevent the Paf-mediated PLD activity and CL
      response (IC(50) of 2 microM). Interestingly, both GKB and Paf-induced CL
      response were prevented by selective Paf antagonists such as CV 6209 or WEB 2086
      indicating that GKB may directly activate Paf receptors. Finally, GKB potentiated
      the CL response induced by fMet-Leu-Phe and zymosan. These results show that GKB
      is the first partial agonist of the Paf receptor described so far capable of
      priming the polymorphonuclear leukocyte function.

PMID- 11960601
TI  - Induction of G(2)/M arrest and inhibition of c-myc and p53 transcription by WP631
      in Jurkat T lymphocytes.
AB  - WP631, a new DNA-binding drug that bisintercalates into DNA with high affinity,
      seems to be highly cytotoxic against Jurkat T lymphocytes. The purpose of this
      study was to gain new insights into the mechanisms by which WP631 halts
      proliferation in this cell type. Treating Jurkat cells with nanomolar
      concentrations of WP631 produced G(2)/M arrest, inhibited the transcription of c
      myc and p53 genes, and induced limited apoptosis during the duration of
      treatment. Suppression of c-myc and p53 expression, and time-dependent decline in
      c-Myc and p53 protein levels, was associated with growth arrest. A weak
      interdependence was also found between the potent antiproliferative activity and
      the apoptotic response; treatment with WP631 for 24-36hr produced arrest in
      G(2)/M and allowed for partial DNA repair. Longer treatments with WP631 allowed
      some repaired cells to re-enter the cell cycle, but produced aneuploidy or
      apoptosis in others.

PMID- 11960602
TI  - Obligatory role of membrane events in the regulatory effect of metformin on the
      respiratory chain function.
AB  - From recent findings about the indirect effect of metformin (MET) targeted on the
      respiratory chain complex I, we reconsidered this question and tried to determine
      the causality of any alteration at this enzymatic level using Xenopus laevis
      oocytes. Addition of MET (50 microM) reduced by 40% the rotenone-sensitive
      activity of complex I only in incubating intact oocytes but not in mitochondria
      isolated by differential centrifugation. The drug prior injected inside these
      cells had also no measurable effect. In spite of this and the weak binding of MET
      to the mitochondrial fraction, there was a fairly good correlation between the
      marked inhibitory action of MET on complex I and its progressive appearance
      within the oocyte cytoplasm. The intriguing observation that MET as a liposomal
      form was again able to exert its role when added directly to isolated
      mitochondria is in accordance with a membrane-mediated uptake and vesicular
      routing of MET. Furthermore, a temperature-dependent effect was clearly shown. At
      4 degrees, oocytes failed to take up efficiently MET and accordingly its
      subsequent action on respiration was therefore lost. Likewise, MET transport was
      hindered and inhibition of complex I totally disappeared when a structural
      analog, asymmetrical dimethylarginine (ADMA), was placed together with MET either
      at an identical concentration or in excess. These data strongly support the view
      that MET may recognise some specific membranous sites, likely belonging to
      effector systems, before penetrating the cell in a bound state via an obscure
      endocytotic event which still has to be identified.

PMID- 11960603
TI  - Distinct binding properties of the AT(1) receptor antagonist [(3)H]candesartan to
      intact cells and membrane preparations.
AB  - [(3)H]-2-Ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benzimidazoline
      7-carboxylic acid ([(3)H]candesartan), a non-peptide angiotensin II type 1
      receptor (AT(1) receptor) antagonist bound with high affinity and specificity to
      intact adherent human AT(1) receptor transfected Chinese hamster ovary cells. The
      binding characteristics were preserved when cells were suspended, but the
      dissociation was 3-4-fold faster and the affinity 2-fold lower, while examining
      [(3)H]candesartan binding to cell membranes. These data suggested the role of the
      intracellular organisation of living CHO-hAT(1) cells in antagonist-AT(1)
      receptor interactions. Yet, a specific role of microtubule or actin filaments of
      the cytoskeleton, receptor phosphorylation by Protein Kinase C, membrane
      polarity, cytoplasmic components like ATP and the need of an intact cell membrane
      could be excluded. The potential effect of protease degradation or receptor
      oxidation during the membrane preparation was also unlikely. The dissociation
      rate and the equilibrium dissociation constant of [(3)H]candesartan increased
      with the temperature for both intact cells and membranes. Thermodynamic studies
      suggested that the bonds between candesartan and the hAT(1) receptor may be of
      different nature in intact CHO-hAT(1) cells and membranes thereof. Whereas the
      binding was almost completely enthalpy-driven on intact cells, there was a mixed
      contribution of both enthalpy and entropy on membranes.

PMID- 11960604
TI  - Troglitazone does not protect rat pancreatic beta cells against free fatty acid
      induced cytotoxicity.
AB  - Thiazolidinediones are a novel class of antidiabetic drugs that reduce insulin
      resistance through interaction with nuclear peroxisome proliferator-activated
      receptor (PPAR)gamma. One of these agents, troglitazone, was also proposed to
      protect beta cells against FFA-induced toxicity, but this effect has not yet been
      directly demonstrated. We recently reported in vitro conditions under which free
      fatty acids (FFA) cause beta cell death by necrosis or apoptosis. The present
      study investigates whether troglitazone (10 microM) interferes with this FFA
      induced toxicity. Addition of this compound did not protect against oleate- or
      palmitate-induced toxicity. On the contrary, it increased palmitate-induced
      necrosis during the first two days of culture, and elevated (increase by 10-20%,
      P<0.05) both oleate- and palmitate-induced apoptosis after 8 days. These results
      do not support the view that troglitazone exerts a direct protective effect on
      beta cells that are exposed to cytotoxic FFA concentrations. They instead
      indicate that the agent may sensitize pancreatic beta cells to FFA-induced
      damage, raising the possibility that its use facilitates the deleterious effect
      of increased FFA levels on the pancreatic beta cell mass.

PMID- 11960605
TI  - Effect of protein-bound uraemic toxins on the thermodynamic characteristics of
      human albumin.
AB  - The ability of albumin to bind drugs and other lipophilic organic acids is
      decreased in chronic renal failure by the accumulation of albumin-bound uraemic
      toxins such as hippuric acid, indoxyl sulphate and 3-carboxy-4-methyl-5-propyl-2
      furanpropanoic acid (CMPF). This furan acid is the most highly bound and is not
      removed by haemodialysis. The inhibitory effects of these three uraemic toxins on
      the interaction of three marker ligands sodium octanoate (for medium chain fatty
      acids), salicylic acid and phenol red (bilirubin site/site I) with albumin have
      been investigated by differential scanning microcalorimetry and flow
      microcalorimetry. CMPF was the most potent inhibitor and its binding site
      coincided with that of bilirubin (site I). Indoxyl sulphate binds to the site for
      medium-chain fatty acids and tryptophan (site II) and hippuric acid, the weakest
      inhibitor, inhibited binding to the salicylic acid site.

PMID- 11960606
TI  - Dose-dependent cysteine-mediated protection of insulin-producing cells from
      damage by hydrogen peroxide.
AB  - AIMS/HYPOTHESIS: Oxidative damage is believed to play a key role in the process
      of pancreatic beta cell destruction leading to type 1 diabetes. The beta cells
      are sensitive to oxidative stress because their intracellular anti-oxidative
      defence mechanisms are weak. The defence mechanisms depend heavily on
      glutathione, the synthesis of which is dependent on the availability of cysteine.
      We investigated whether an increased amount of cysteine available could protect
      beta cells from oxidative damage. METHODS: Rat insulinoma cells (RINm5F) were
      exposed to 50 or 100 microM hydrogen peroxide in the presence of three different
      cysteine concentrations (0.1, 1 and 5mM). Cell viability was analyzed by vital
      staining and the cellular metabolic status by C,N-diphenyl-N'-4,5-dimethyl
      thiazol-2-yl tetrazolium bromide (MTT) analysis. Intracellular insulin, DNA and
      glutathione contents were measured. The mechanism of death was further clarified
      by gel electrophoretic DNA fragmentation analysis. RESULTS: Hydrogen peroxide
      decreased cell viability and induced functional impairment. Vital staining
      indicated that 1mM cysteine effectively protected the cells. The protective
      effect was confirmed by the MTT assay showing preserved metabolic integrity, and
      by measurements of intact intracellular insulin and DNA content. Cysteine
      increased intracellular glutathione. Gel electrophoretic analysis of DNA revealed
      hydrogen peroxide-induced apoptotic fragmentation. This was also abolished by 1mM
      cysteine. The therapeutic window of cysteine was narrow: 0.1mM cysteine provided
      inadequate protection, and 5mM cysteine was already toxic in this setting.
      CONCLUSION: A proper dose of cysteine could provide a safe and effective means to
      protect beta cells from oxidative damage.

PMID- 11960607
TI  - Modulation of apoptosis and improved redox metabolism with the use of a new
      antioxidant formula.
AB  - Oxidative stress is involved in the pathogenesis of a wide spectrum of diseases,
      implicating that strategies directed at counterbalancing oxidative processes
      could have a role in clinical medicine. There is also an evidence that oxidative
      stress acts as a major determinant of apoptotic cell death. Many studies have
      reported favourable effects of antioxidant formulas on several parameters of the
      oxidant-antioxidant balance, but none of them has focused whether antioxidant
      formulas could modulate apoptosis. We investigated in 20 healthy individuals the
      effect of supplementation with a formula containing alpha-tocopherol, alpha
      lipoic acid, coenzyme Q(10), carnitines, and selenomethionine, on plasma oxidant
      status and peroxide levels, erythrocyte antioxidant enzymes, lymphocyte
      apoptosis, and generation of ROS at the mitochondrial level. Control subjects
      received only carnitines or an incomplete formula with alpha-tocopherol, alpha
      lipoic acid, coenzyme Q(10), and selenomethionine. Supplementation with the
      complete formula resulted in a significant increase in the plasma antioxidant
      status that was mirrored by a decrease in blood peroxide levels and a reduced
      generation of ROS at the mitochondrial level. This was associated with a
      significant decrease in the frequency of peripheral blood lymphocytes, with
      either CD4 or CD8 phenotype, undergoing apoptosis. Less consistent results were
      found when either incomplete formula was used. Our study suggests that
      supplementation with antioxidant formulas can modulate the process of apoptosis
      under in vivo conditions. The clinical potential of this strategy in the
      treatment of diseases with an elevated commitment to apoptosis should be
      explored.

PMID- 11960608
TI  - A selective plasmin inhibitor, trans-aminomethylcyclohexanecarbonyl-L-(O
      picolyl)tyrosine-octylamide (YO-2), induces thymocyte apoptosis.
AB  - The treatment of rat thymocytes with YO-2, a novel inhibitor of plasmin, resulted
      in an increase in DNA fragmentation. DNA fragmentation was also induced by
      another YO compounds such as YO-0, -3, -4 and -5. These YO compounds are the
      inhibitor of plasmin activity. On the other hand, YO-1, -6 and -8 that hardly
      inhibit plasmin activity had no effect on DNA fragmentation. Analysis of
      fragmented DNA from thymocytes treated with YO-2 by agarose gel electrophoresis
      revealed that the compound caused internucleosomal DNA fragmentation. In
      addition, judging from a laser scanning microscopy, annexin V-positive and
      propidium iodide-negative cells were increased by the treatment of the cells with
      the compound. Moreover, chromatin condensation was observed in thymocytes treated
      with the compound. These results demonstrated that YO-2 induces thymocyte
      apoptosis. There seemed to be some correlation between the apoptosis induced by
      YO compounds and their plasmin inhibitory effect. However, because the other
      protease inhibitors including pepstatin A, leupeptin, AEBSF, DFP and E-64-d did
      not affect DNA fragmentation, YO compounds are likely to have unique mechanism on
      plasmin or to show the effect on the other plasmin-like proteases. The plasmin
      inhibitory activity may have an important role in YO-2-induced apoptosis.
      Furthermore, the stimulations of caspase-8, -9 and -3-like activities were
      observed in thymocytes treated with YO-2. These results suggest that YO-2 induces
      thymocyte apoptosis via activation of caspase cascade.

PMID- 11960609
TI  - Protection by ascorbic acid from denaturation and release of cytochrome c,
      alteration of mitochondrial membrane potential and activation of multiple
      caspases induced by H(2)O(2), in human leukemia cells.
AB  - We investigated peroxide and superoxide accumulation, cytochrome c nature and
      release from mitochondria, as well as caspase activation during exposure of HL-60
      cells to H(2)O(2) and the protective effect of ascorbic acid. Exposure of the
      cells to 100 microM H(2)O(2) resulted in intracellular accumulation of peroxides,
      denaturation of cytochrome c that was identified in the mitochondria and cytosol,
      release of native cytochrome c to the cytosol and fall in mitochondrial membrane
      potential (DeltaPsi(m)). Loading of cells with ascorbic acid before exposure to
      H(2)O(2) resulted in a dose-dependent protective effect against: intracellular
      accumulation of peroxides, DeltaPsi(m) alteration, cytochrome c denaturation and
      release. The accumulation of peroxides induced processings and activations of
      procaspase-8, -9 and -3. Double staining with antiserum which recognizes the p18
      subunit of cleaved caspase-3 and with Hoechst had shown that a high percentage of
      cells exposed to 100 microM H(2)O(2) stained positively with the antibody and
      showed features of apoptosis. Ascorbic acid loading prevented caspase activation
      induced by H(2)O(2). We conclude that ascorbic acid protects against activation
      of apoptotic cascades in HL-60 cells exposed to H(2)O(2) and against apoptosis.

PMID- 11960610
TI  - Stem cell toxicity of oxazaphosphorine metabolites in comparison to their
      antileukemic activity.
AB  - The oxazaphosphorine agent cyclophosphamide (CP) is an alkylating agent with a
      relative low stem cell toxicity. The aim of this study was to further evaluate
      the stem cell toxicity of the active metabolites of CP and its structural
      analogue ifosfamide (IFO) in comparison to their antileukemic efficacy. Cells of
      different malignant hematologic disorders (HL-60, HS-Sultan and THP-1) and CD34+
      stem cells were treated with cytotoxic CP-metabolite mafosfamide (MAFO) and IFO
      metabolites 4-hydroxy-IFO (4-OH-IFO) and chloroacetaldehyde. The clonogenity of
      the cells was investigated by using a colony-forming assay. All metabolites
      reduced the formation of both tumor-derived colonies and stem cell-derived CFU
      GMs in a concentration-dependent manner. Our data showed a relative tumor
      specific, stem cell protecting action of the substances tested with a higher
      toxicity against tumor cells (IC(50) against HS-Sultan: MAFO 1.1 microM; 4-OH-IFO
      1.3 microM; CAA 3 microM) than against stem cells (IC(50) MAFO 14.8 microM; 4-OH
      IFO 16.9 microM; CAA 14 microM). However, while the cytotoxic action of 4-OH-IFO
      corresponded to MAFOs activity, CAAs cytotoxic effect against the hematologic
      tumor cells was lower. In conclusion, the results confirm the observed
      cytotoxicity of CAA against solid tumors for cells of malignant hematologic
      disorders. Although the relative cytotoxic specificity of CAA is lower than for 4
      OH-IFO and MAFO, also CAA, like 4-OH-IFO and MAFO, was found to be in part a
      tumoricidal, stem cell protecting substance.

PMID- 11960611
TI  - Modulation of dendritic release of dopamine by metabotropic glutamate receptors
      in rat substantia nigra.
AB  - A superfusion system was used to study the effects of metabotropic glutamate
      receptor (mGluR) ligands upon the release of [(3)H]dopamine ([(3)H]DA) previously
      taken up by rat substantia nigra (SN) slices. trans-(+/-)-1-Amino-(1S,3R)
      cyclopentane dicarboxylic acid (trans-ACPD; 100 and 600 microM), a group I and II
      mGluR agonist, evoked the release of [(3)H]DA from nigral slices. This last
      effect was reduced significantly by (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)
      glycine (MCCG; 300 microM), an antagonist of group II mGluR, or by the addition
      of tetrodotoxin (D-APV; 1 microM) to the superfusion medium. D-(-)-2-Amino-5
      phosphono-valeric acid (100 microM), an N-methyl-D-aspartate receptor antagonist,
      or the presence of Mg(2+) (1.2mM) in the superfusion medium did not modify trans
      ACPD-induced [(3)H]DA release. In addition, a group II mGluR agonist such as
      (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV; 100 microM)
      significantly induced the release of [(3)H]DA from nigral slices, whereas a group
      I mGluR agonist such as (RS)-3,5-dihydroxyphenylglycine (DHPG; 50 and 100 microM)
      did not modify the release of the [(3)H]-amine. Further experiments showed that
      the NMDA (100 microM)-evoked release of [(3)H]DA was decreased significantly by
      prior exposure of SN slices to trans-ACPD. Finally, partial denervation of the DA
      nigro-striatal pathway with 6-hydroxydopamine (6-OH-DA) increased trans-ACPD
      induced release of [(3)H]DA, whereas it decreased trans-ACPD inhibitory effects
      on NMDA-evoked release of [(3)H]DA from nigral slices. The present results
      suggest that the dendritic release of DA in the SN is regulated by mGluR
      activation. Such nigral mGluR activation may produce opposite effects upon basal
      and NMDA-evoked release of DA in the SN. In addition, such mGluR-induced effects
      in the SN are modified in response to partial denervation of the DA nigro
      striatal pathway.

PMID- 11960612
TI  - Developmental regulation of flavin-containing monooxygenase form 1 in the liver
      and kidney of fetal and neonatal rabbits.
AB  - Flavin-containing monooxygenases (FMOs) comprise a multi-gene family and catalyze
      the oxygenation of soft nucleophilic sulfur, nitrogen, phosphorus, and selenium
      in xenobiotics. Previous studies have demonstrated that FMO is regulated
      developmentally and by the administration of certain steroid hormones. This study
      examined the expression of FMO form 1 in the livers and kidneys of fetal and
      neonatal rabbits, from day 25 of gestation through 3 weeks of age, by assaying
      FMO1 mRNA and protein levels, as well as catalytic activity. FMO1 mRNA and
      protein expression and FMO catalytic activity were present in fetal livers at the
      earliest time point measured (day 25 of gestation), although at levels
      approximately 10% of that found in adult livers. Hepatic FMO1 mRNA levels
      increased during and after gestation; levels were not significantly different
      from those measured in adult male livers. FMO1 protein content and activity rose
      rapidly after birth to reach 70-80% of adult levels by 3 weeks of age. The
      expression of FMO1 in fetal and neonatal kidneys was markedly lower than in
      liver. FMO1 mRNA levels never averaged more than 3.4% of adult male liver levels,
      but did not differ from adult kidney levels at any of the points measured.
      Protein levels and enzyme activity rose significantly after birth to
      approximately 30% of the level in adult kidneys by 3 weeks of age. The early
      developmental appearance of FMO1 suggests a possible role in the metabolism of
      xenobiotics through transplacental or lactational exposures.

PMID- 11960613
TI  - Modulation of the beta-adrenergic receptor system of vascular smooth muscle cells
      in vitro and in vivo by chronically elevated endothelin-1 levels.
AB  - Endothelin-1 (ET-1) levels are chronically elevated in several cardiovascular
      diseases and correlate with an increased mortality. However, in contrast to acute
      biological activities such as vasoconstriction, little is known about long-term
      effects of ET-1. In this study we determined the effects of ET-1 on the beta(2)
      adrenergic receptor (AR) system. Incubation of smooth muscle cells with ET-1 for
      72 hr led to increased beta(2)AR density as determined by radioligand binding.
      Experiments with inhibitors of protein and RNA synthesis as well as RT-PCR
      revealed that beta(2)AR upregulation required de novo synthesis. In addition,
      protein kinase C but neither NO nor prostaglandin metabolism were involved in
      this effect. The enhanced expression of beta(2)AR was associated with an
      increased expression of its stimulatory G-protein and the receptor's ability to
      stimulate adenylyl cyclase. To study chronic effects of ET-1 in vivo, rats were
      infused with ET-1 for 3 weeks. Similarly as in cultured cells, prolonged ET-1
      exposure led to increased betaAR expression in vivo. As a consequence, beta(2)AR
      induced vasodilatation was increased in aortic rings from ET-1-treated animals.
      Our results therefore suggest that chronically elevated ET-1 levels in vitro and
      in vivo induce counterregulatory mechanisms by increasing betaARs that attenuate
      the vasoconstrictive effects of ET-1.

PMID- 11960614
TI  - Inhibition of gluconeogenesis by vanadium and metformin in kidney-cortex tubules
      isolated from control and diabetic rabbits.
AB  - Effect of vanadyl acetylacetonate (VAc) and metformin on gluconeogenesis has been
      studied in isolated hepatocytes and kidney-cortex tubules of rabbit. Glucose
      formation from alanine+glycerol+octanoate, pyruvate or dihydroxyacetone was
      inhibited by 50-80% by 100 microM VAc or 500 microM metformin in renal tubules of
      control and alloxan-diabetic animals, while the inhibitory action of these
      compounds in hepatocytes was less pronounced (by about 20-30%). In contrast to
      VAc, metformin increased the rate of lactate formation by about 2-fold in renal
      tubules incubated with alanine+glycerol+octanoate. In view of VAc-induced changes
      in intracellular gluconeogenic intermediates and gluconeogenic enzyme activities,
      it is likely that this compound may decrease fluxes through pyruvate carboxylase,
      phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6
      phosphatase. In contrast to VAc, metformin-induced decrease in renal
      gluconeogenesis may result from a decline of cytosolic oxaloacetate level and
      consequently PEPCK activity. Following 6 days of VAc administration (1.275 mg
      Vkg(-1) body weight daily) the blood glucose level in alloxan-diabetic rabbits
      was normalised while blood glucose changes in control animals were not observed.
      On the contrary, in diabetic animals treated for 6 days with metformin (200 mg
      kg(-1) body weight day(-1)) a high blood glucose level was maintained.
      Unfortunately, VAc-treated control and diabetic rabbits exhibited elevated serum
      urea and creatinine levels. In VAc-treated animals vanadium was accumulated in
      kidney-cortex up to 7.6+/-0.6 microg Vg(-1) dry weight. In view of a potential
      vanadium nephrotoxicity a therapeutic application of vanadium compounds needs a
      critical re-evaluation.

PMID- 11960616
TI  - Rapid activation of endothelial NO synthase by estrogen: evidence for a steroid
      receptor fast-action complex (SRFC) in caveolae.
AB  - Estrogen has important atheroprotective and vasoactive properties related to its
      capacity to stimulate nitric oxide (NO) production by endothelial NO synthase.
      Previous work has shown that these effects are mediated by estrogen receptor (ER)
      alpha functioning in a nongenomic manner via calcium-dependent, MAP kinase
      dependent mechanisms. Recent studies have demonstrated that estradiol (E(2))
      activates eNOS in isolated endothelial plasma membranes in the absence of added
      calcium, calmodulin or eNOS cofactors. Studies of blockade by ICI 182,780 and by
      ER alpha antibody, and also immunoidentification experiments indicate that the
      process is mediated by a subpopulation of plasma membrane-associated ER alpha.
      Fractionation of endothelial cell plasma membranes has further revealed that ER
      alpha protein is localized to caveolae, and that E(2) causes stimulation of eNOS
      in isolated caveolae which is ER-dependent and calcium-dependent, whereas
      noncaveolae membranes are insensitive. Furthermore, in intact endothelial cells
      the activation of eNOS by E(2) is prevented by pertussis toxin, and exogenous GDP
      beta S inhibits the response in isolated plasma membranes. Coimmunoprecipitation
      studies have shown that E(2) exposure causes interaction between ER alpha and
      G(alpha i) on the plasma membrane, and eNOS activation by E(2) is enhanced by
      overexpression of G(alpha i) and attenuated by expression of a protein regulator
      of G protein signaling (RGS), RGS4. Thus, a subpopulation of ER alpha is
      localized to caveolae in endothelial cells, where they are coupled via G(alpha i)
      to eNOS in a functional signaling module. Emphasizing the dependence on cell
      surface-associated receptors, these observations provide evidence for the
      existence of a steroid receptor fast-action complex, or SRFC, in caveolae.

PMID- 11960617
TI  - Membrane mediated signaling mechanisms are used differentially by metabolites of
      vitamin D(3) in musculoskeletal cells.
AB  - 1 alpha,25(OH)(2)D(3) and 24R,25(OH)(2)D(3) mediate their effects on chondrocytes
      and osteoblasts in part through increased activity of protein kinase C (PKC). For
      both cell types, 1 alpha,25(OH)(2)D(3) exerts its effects primarily on more
      mature cells within the lineage, whereas 24R,25(OH)(2)D(3) exerts its effects
      primarily on relatively immature cells. Studies using the rat costochondral
      cartilage growth plate as a model indicate that the two metabolites increase PKC
      activity by different mechanisms. In growth zone cells (prehypertrophic/upper
      hypertrophic cell zones), 1 alpha,25(OH)(2)D(3) causes a rapid increase in PKC
      that does not involve new gene expression. 1 alpha,25(OH)(2)D(3) binds its
      membrane receptor (1,25-mVDR), resulting in activation of phospholipase A(2) and
      the rapid release of arachidonic acid, as well as activation of
      phosphatidylinositol-specific phospholipase C, resulting in formation of
      diacylglycerol and inositol-1,4,5-tris phosphate (IP(3)). IP(3) leads to release
      of intracellular Ca(2+) from the rough endoplasmic reticulum, and together with
      diacylglycerol, the increased Ca(2+) activates PKC. PKC is then translocated to
      the plasma membrane, where it initiates a phosphorylation cascade, ultimately
      phosphorylating the extracellular signal-regulated kinase-1 and -2 (ERK1/2)
      family of MAP kinases (MAPK). PKC increases are maximal at 9 min, and MAPK
      increases are maximal at 90 min in these cells. By contrast, 24R,25(OH)(2)D(3)
      increases PKC through activation of phospholipase D in resting zone cells. Peak
      production of diacylglycerol via phospholipase D2 is at 90 min, as are peak
      increases in PKC. Some of the effect is direct on existing plasma membrane PKC,
      but most is due to new PKC expression; translocation is not involved. Arachidonic
      acid and its metabolites also play differential roles in the mechanisms,
      stimulating PKC in growth zone cells and inhibiting PKC in resting zone cells.
      24R,25(OH)(2)D(3) decreases phospholipase A(2) activity and prostaglandin
      production, thereby overcoming this potential inhibitory component, which may
      account for the delay in the PKC response. Ultimately, ERK1/2 is phosphorylated.
      PKC-dependent MAPK activity transduces some, but not all, of the physiological
      responses of each cell type to its respective vitamin D metabolite, suggesting
      that the membrane receptor(s) and nuclear receptor(s) may function
      interdependently to regulate proliferation and differentiation of musculoskeletal
      cells, but different pathways are involved at different stages of phenotypic
      maturation.

PMID- 11960618
TI  - The dynamic and elusive membrane estrogen receptor-alpha.
AB  - Many studies have demonstrated the nuclear forms of steroid receptors and their
      activities, while fewer investigators have identified and described the membrane
      forms of these receptors. Our immuno-identification approaches for the
      qualitative and quantitative comparison of the membrane form of the estrogen
      receptor-alpha (mER alpha) to its nuclear counterpart now allow us to address
      questions about the comparative levels and regulation of these receptor forms. ER
      alpha-specific antisense oligonucleotides eliminate mER alpha expression, while
      only mildly reducing the nuclear ER alpha. Success of immuno-identification for
      the mER alpha is very sensitive to different fixation protocols, affecting cell
      permeability (and thus distinction from the intracellular form) and differential
      epitope preservation. All such identifications must be accompanied by proof of
      cell membrane integrity and focal plane assessments. The mER alpha expression on
      selected cells declines rapidly with cell passage number and cell density.
      Expression of mER alpha is enhanced by serum starvation and selection for
      specific phases of the cell cycle. The hinge region of the protein is sensitive
      to ligand-induced epitope masking and to antibody-induced changes in receptor
      mediated responses. Responsive cells are often diluted within cell populations by
      loss of the membrane receptor form. The bimodality of the rapid estrogen action,
      with inhibitory doses between picomolar and nanomolar stimulatory concentrations,
      requires detailed dose-response curves. Finally, responsive cells can be lost
      from assays, as upon estrogen treatment they rapidly round up and leave the
      substrates to which they are attached. These regulatory phenomena demonstrate
      that levels of the membrane form of the estrogen receptor are very dynamic.

PMID- 11960619
TI  - Activation of Maxi Cl(-) channels by antiestrogens and phenothiazines in NIH3T3
      fibroblasts.
AB  - The identification of alternative estrogen actions has been accumulating steadily
      over the past two decades. Typically, these novel actions are not directly
      related to nuclear transcriptional events but related to the interaction of
      estrogens with sites present at plasma membrane or cytosolic locations. These
      alternative effects, widely known as non-genomic effects, range from the
      modulation of plasma membrane ion channel activity to the regulation of different
      intracellular signalling cascades. In the present study we have investigated the
      modulation of a large conductance chloride channel (Maxi Cl(-)) by estrogens, non
      steroidal triphenylethylene antiestrogens and phenothiazines in NIH3T3
      fibroblasts and the dependence on guanosine triphosphate (GTP) of the Maxi Cl(-)
      activation. Our data identifies the non-steroidal antiestrogens toremifene and
      tamoxifen, and the phenothiazines chlorpromazine and triflupromazine as
      activators of Maxi Cl(-) channels. In contrast, 17 beta-estradiol and cAMP, added
      prior to the exposure to antiestrogens, prevent channel activation. The pure
      antiestrogen ICI 182780 did not activate the channel nor prevent its activation
      by non-steroidal antiestrogens. The activation of Maxi Cl(-) channels by
      toremifene and tamoxifen required the presence of intracellular nucleotides and
      was inhibited by the stable analog, GDP beta -S, suggesting the participation of
      a G-protein in the activation process. Little is known about the physiological
      relevance of Maxi Cl(-) channels. However, that fact that its regulation by
      estrogens and antiestrogens is shared by different cell types might imply a
      common role which needs to be identified.

PMID- 11960620
TI  - Estrogen modulation of K(+) channel activity in hypothalamic neurons involved in
      the control of the reproductive axis.
AB  - Here we report on the progress we have made in elucidating the mechanisms through
      which estrogen alters synaptic responses in hypothalamic neurons. We examined the
      modulation by estrogen of the coupling of various receptor systems to inwardly
      rectifying and small conductance, Ca(2+)-activated K(+) (SK) channels. We used
      intracellular sharp-electrode and whole-cell recordings in hypothalamic slices
      from ovariectomized female guinea pigs. Estrogen rapidly uncouples mu-opioid
      receptors from G protein-gated inwardly rectifying K(+) (GIRK) channels in beta
      endorphin neurons, manifest by a reduction in the potency of mu-opioid receptor
      agonists to hyperpolarize these cells. This effect is blocked by inhibitors of
      protein kinase A and protein kinase C. Estrogen also uncouples gamma-aminobutyric
      acid (GABA)(B) receptors from the same population of GIRK channels coupled to mu
      opioid receptors. At 24 h after steroid administration, the GABA(B)/GIRK channel
      uncoupling observed in GABAergic neurons of the preoptic area (POA) is associated
      with reduced agonist efficacy. Conversely, estrogen enhances the efficacy of
      alpha(1)-adrenergic receptor agonists to inhibit apamin-sensitive SK currents in
      these POA GABAergic neurons, and does so in both a rapid and sustained fashion.
      Finally, we observed a direct, steroid-induced hyperpolarization of both arcuate
      and POA neurons, among which gonadotropin-releasing hormone (GnRH) neurons are
      particularly sensitive. These findings indicate a richly complex yet coordinated
      steroid modulation of K(+) channel activity that serves to control the
      excitability of hypothalamic neurons involved in regulating the reproductive
      axis.

PMID- 11960621
TI  - Molecular tools for study of genomic and rapid signal transduction responses
      initiated by 1 alpha,25(OH)(2)-vitamin D(3).
AB  - The steroid hormone 1 alpha,25(OH)(2)-vitamin D(3) [1 alpha,25(OH)(2)D(3)]
      mediates through its widely distributed nuclear receptor (VDR(nuc)) regulation of
      gene transcription (genomic responses) and through a putative membrane receptor
      (VDR(mem)) a variety of rapid responses. Rapid responses studied in our
      laboratories include opening of voltage-gated calcium and chloride channels in
      ROS 17/2.8 osteoblast cells, activation of MAP-kinase in human leukemia NB4 cells
      and chick intestinal cells, release of insulin by rat pancreatic beta-cells, and
      in chick duodena transcaltachia (the rapid hormonal stimulation of intestinal
      Ca(2+) transport). 1 alpha,25(OH)(2)D(3) is conformationally flexible (side
      chain, seco B-ring and A-ring) and accordingly is able to generate a large array
      of different shapes to serve as ligands for available receptors (VDR(nuc) and
      VDR(mem)) in the vitamin D endocrine system. Our laboratories have utilized a
      number of conformationally restricted analogs of 1 alpha,25(OH)(2)D(3) (from a
      library of several hundred analogs) to evaluate the preferred shape of the
      ligands for rapid and genomic responses. The determination of the X-ray structure
      of the 1 alpha,25(OH)(2)D(3)-occupied VDR(nuc) revealed that the preferred ligand
      shape was a twisted 6-s-trans bowl shape [Molecular Cell 5 (2000) 173-179].
      Optimal agonists for genomic responses include 1 alpha,25(OH)(2)D(3) and other
      side chain conformationally flexible analogs such as 20-epi-1 alpha,25(OH)(2)D(3)
      [approximately equal to 200-500-fold more potent than 1 alpha,25(OH)(2)D(3)] and
      21-(3'-hydroxy-3-methylbutyl)-1 alpha,25(OH)(2)D(3) [an analog with two side
      chains] all which can achieve the preferred VDR(nuc) shape. In contrast, rapid
      responses require a 6-s-cis shape of the agonist ligand such as can be achieved
      by the natural hormone 1 alpha,25(OH)(2)D(3) or by analogs permanently locked in
      the 6-s-cis shape such as 1 alpha,25(OH)(2)lumisterol(3) or 1 alpha,25(OH)(2)-7
      dehydrocholesterol. Additionally, we have discovered analogs that are specific in
      their antagonist properties for either rapid or genomic responses. Thus, 1
      beta,25(OH)(2)D(3) is an antagonist of only rapid responses [via the VDR(mem)],
      while 23S-25-dehydro-1 alpha,25(OH)D(3)-26,23-lactone is an antagonist of only
      nuclear responses [via the VDR(nuc)]. In conclusion, we have presented evidence
      that 1 alpha,25(OH)(2)D(3) mediated rapid response and genomic response signal
      transduction pathways utilize differing shapes of ligand, both as agonists and
      antagonists.

PMID- 11960622
TI  - Microarray detection of gene expression changes induced by 1,25(OH)(2)D(3) and a
      Ca(2+) influx-activating analog in osteoblastic ROS 17/2.8 cells.
AB  - 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) treatment of osteoblastic ROS 17/2.8
      cells initiates membrane-initiated rapid responses through activation of Ca(2+)
      influx and longer-term nuclear receptor-mediated changes in gene expression.
      Ca(2+) influx triggers a change in the phosphorylation state of the bone matrix
      protein, osteopontin (OPN), detectable at 3 h and prior to nuclear receptor
      mediated events. This study aimed to determine if Ca(2+) influx induced by
      1,25(OH)(2)D(3) would produce nuclear receptor-independent changes in gene
      expression. We employed a rat cDNA microarray strategy to screen the
      transcriptional changes at 3 h of treatment with 1,25(OH)(2)D(3) and with an
      analog of 1,25(OH)(2)D(3) (25(OH)-16ene-23yne-D(3) [AT]) that we previously
      showed to activate Ca(2+) influx without binding to the nuclear receptor. Arrays
      also were screened with cDNA from ROS 17/2.8 cells treated for 24 h, when nuclear
      receptor-mediated transcriptional events would occur. Rat gene filters
      (GeneFilter, Research Genetics) were hybridized with labeled cDNA probes from
      treatment groups. Among 5000 different clones on the array filters, we identified
      a family of genes which were altered 2-fold or greater following treatment with
      1,25(OH)(2)D(3) or analog AT for 3 h. Cluster analysis also revealed genes whose
      expression was significantly up-regulated at 24 h, including OPN. Analysis of
      rapid changes in gene expression revealed changes affecting a diverse range of
      cellular pathways and functions, including protein kinases and phosphatases,
      Ca(2+) signaling, cell adhesion and secretion. These findings provide clear
      evidence of rapid changes in gene expression associated with Ca(2+) influx
      mediated by 1,25(OH)(2)D(3), and shed light on the nuclear-receptor independent
      signaling pathway affecting OPN phosphorylation.

PMID- 11960623
TI  - Cellular functions of plasma membrane estrogen receptors.
AB  - Strong evidence now exists for the presence and importance of plasma membrane
      estrogen receptors (ER) in a variety of cells that are targets for steroid
      action. When estradiol (E2) binds cell surface proteins, the initiation of signal
      transduction triggers downstream signaling cascades that contribute to important
      functions. These functions include cell growth and survival, migration, and new
      blood vessel formation. In some instances these effects result from the
      initiation of gene transcription, upregulated through signaling from the
      membrane. The membrane ER probably originates from the same gene and transcript
      that produces the nuclear receptor. In the membrane, ER appear to localize mainly
      to discrete domains of the plasma membrane, known as caveolae, but the mechanisms
      by which this small pool of ER translocates to this site are currently unknown.
      At the caveolae, a cross talk with signaling molecules facilitates E2/ER cell
      biologic actions. This both includes direct stimulation of signaling via G
      protein activation, and a cross-activation of the epidermal growth factor
      receptor (EGFR). This review article highlights some of the important advances in
      understanding the cell biology of estrogen action that emanates from the
      membrane.

PMID- 11960624
TI  - Non-genomic stimulation of tyrosine phosphorylation cascades by 1,25(OH)(2)D(3)
      by VDR-dependent and -independent mechanisms in muscle cells.
AB  - Studies with different cell types have shown that modulation of various of the
      fast as well as long-term responses to 1,25(OH)(2)D(3) depends on the activation
      of tyrosine kinase pathways. Recent investigations of our laboratory have
      demonstrated that 1,25(OH)(2)D(3) rapidly stimulates in muscle cells tyrosine
      phosphorylation of PLC-gamma and the growth-related proteins MAPK and c-myc. We
      have now obtained evidence using antisense technology indicating that VDR
      dependent activation of Src mediates the fast stimulation of tyrosine
      phosphorylation of c-myc elicited by the hormone. This non-genomic action of
      1,25(OH)(2)D(3) requires tyrosine phosphorylation of the VDR. Immunoprecipitation
      under native conditions coupled to Western blot analysis revealed 1,25(OH)(2)D(3)
      dependent formation of complexes between Src and the VDR and c-myc. However, the
      activation of MAPK by the hormone was only partially mediated by the VDR and
      required in addition increased PKC and intracellular Ca(2+). Following its
      phosphorylation, MAPK translocates into the nucleus where it regulates c-myc
      transcription. Altogether these results indicate that tyrosine phosphorylation
      plays a role in the stimulation of muscle cell growth by 1,25(OH)(2)D(3). Data
      were also obtained involving tyrosine kinases and the VDR in hormone regulation
      of the Ca(2+) messenger system by mediating the stimulation of store-operated
      calcium (SOC; TRP) channels. Congruent with this action, 1,25(OH)(2)D(3) induces
      a rapid translocation of the VDR to the plasma cell membrane which can be blocked
      by tyrosine kinase inhibitors. Of mechanistic relevance, an association between
      the VDR and TRP proteins with the participation of the scaffold protein INAD was
      shown.

PMID- 11960626
TI  - Nongenomic effects of aldosterone: cellular aspects and clinical implications.
AB  - Nongenomic action of aldosterone has been observed in many cell types which often
      are different from the classic target tissues for mineralocorticoid action, such
      as vascular cells. As judged from their time scale and insensitivity toward
      inhibitors of protein synthesis, effects are not mediated by the classic
      mineralocorticoid receptor pathway. Here we summarize studies on rapid in vitro
      aldosterone effects, e.g. ion fluxes, and second messengers involved therein.
      Furthermore, several clinical studies on in vivo aldosterone action have shown
      rapid effects on cardiovascular parameters, among them baroreflex and vascular
      resistance. Taken together with the beneficial effect of aldosterone antagonism
      in heart failure patients that was demonstrated in the Randomized Aldactone
      Evaluation Study (RALES), aldosterone may be an equally important factor of the
      renin-angiotensin-aldosterone system in cardiovascular pathogenesis.

PMID- 11960625
TI  - Non-genomic convergent and divergent signalling of rapid responses to aldosterone
      and estradiol in mammalian colon.
AB  - Studies from our laboratory have demonstrated rapid ( < 1 min) non-genomic
      activation of Na(+)-H(+) exchange, K(+) recycling, PKC activity and a PKC
      dependent Ca(2+) entry through L-type Ca(2+) channels specifically by
      mineralocorticoids in distal colon. Aldosterone directly stimulates the activity
      of the PKC alpha isoform (but not PKC delta, PKC epsilon and PKC zeta) in a cell
      free assay system containing only purified commercially available enzyme,
      appropriate substrate peptide, co-factors and lipid vesicles. The primary ion
      transport target of the non-genomic signal transduction cascade elicited by
      aldosterone in epithelia is the Na(+)-H(+) exchanger. In isolated colonic crypts,
      aldosterone produced a PKC alpha sensitive intracellular alkalinisation within 1
      min of hormone addition. Intracellular alkalinisation upregulates an ATP
      dependent K(+) channel, which is involved in K(+) recycling to maintain the
      electrical driving force for Na(+) absorption, while inhibiting a Ca(2+) 
      dependent K(+) channel, which generates the charge balance for Cl(-) secretion.
      The non-genomic response to aldosterone in distal colon appears to enhance the
      capacity for absorption while down-regulating the potential for secretion. We
      have also demonstrated rapid (< 1 min) non-genomic activation of Na(+)-H(+)
      exchange, K(+) recycling, PKC alpha activity, and a PKC delta- and PKA-dependent
      Ca(2+) entry through di-hydropyridine-blockable Ca(2+) channels specifically by
      17beta-estradiol in distal colon. These rapid effects are female gender specific
      and are insensitive to inhibitors of the classical estrogen receptor (ER). 17
      beta-Estradiol directly stimulated the activity of both PKC delta and PKC alpha
      (but not PKC epsilon or PKC zeta) in a cell-free assay system. E2 rapidly
      inhibited basolateral K(Ca) channel activity which would be expected to result in
      an acute inhibition of Cl(-) secretion. Physiological concentrations of E2 (0.1
      10 nM) reduced both basal and secretagogue-induced Cl(-) secretion. This anti
      secretory effect of E2 is sensitive to PKC inhibition, intracellular Ca(2+)
      chelation, and is female gender specific and insensitive to inhibitors of the
      classical ER. These observations link rapid non-genomic activation of second
      messengers with a rapid gender-specific physiological effect in the whole tissue.
      Aldosterone and E2 differ in their protein kinase signal transduction and both
      hormones stimulate specific PKC isoforms indicating both common and divergent
      signalling systems for salt-retaining steroid hormones. The physiological
      function of non-genomic effects of aldosterone and estradiol is to shift the
      balance from net secretion to net absorption in a pluripotential epithelium.

PMID- 11960627
TI  - Rapid actions of aldosterone on cells from renal epithelium: the possible role of
      EGF-receptor signaling.
AB  - It has been suggested that steroids interact with peptide hormones in part by
      rapid, potentially non-genomic, mechanisms. The peptide hormone epidermal growth
      factor (EGF) regulates cell proliferation and ion transport using ERK1/2 as
      downstream signal. Furthermore, the EGF-receptor (EGF-R) is involved in signaling
      by G-protein-coupled receptors, growth hormone and cytokines via transactivation.
      We show that aldosterone modulates Na(+)/H(+)-exchange in renal collecting duct
      derived Madin-Darby canine kidney (MDCK) cells via ERK1/2 in a similar way as
      compared to growth factors. Furthermore, we tested the hypothesis that
      aldosterone uses the EGF-R as heterologous signal transducer in MDCK cells.
      Aldosterone induces a rapid increase of ERK1/2 phosphorylation and cytosolic
      Ca(2+)-concentration of similar extend as compared to EGF. Furthermore,
      aldosterone stimulates EGF-R Tyr-phosphorylation. Inhibition of EGF-R kinase
      abolished aldosterone-induced signaling. Aldosterone-induced Ca(2+)-influx seems
      to be mediated by the activation of ERK1/2, whereas ERK1/2 activation does not
      depend on Ca(2+)-influx. Our data show that aldosterone uses the EGF-R-ERK1/2
      signaling cascade to elicit its rapid effects in MDCK cells.

PMID- 11960628
TI  - Characterization of membrane nongenomic receptors for progesterone in human
      spermatozoa.
AB  - Rapid, nongenomic actions of steroid hormones have been characterized only
      recently. They may be mediated by interaction with a poorly characterized
      membrane receptor, by classic receptor located to the plasma membrane, or by
      interaction of the classic receptor with other signaling effectors. Among these,
      rapid effects of progesterone on human spermatozoa have been shown to be mediated
      by interaction with one or more membrane receptors. Two proteins, respectively of
      57 and 28 kDa, representing the possible surface progesterone receptors in human
      spermatozoa, have been identified by our group employing an antibody (c-262)
      directed against the progesterone binding domain of the genomic receptor. The two
      proteins have been immunoprecipitated using c-262, isolated by 2D gel
      electrophoresis and analyzed by Maldi-Tof. Preliminary results of the analysis in
      data bank of the obtained masses suggest that the two proteins represent
      previously unidentified ones since they do not match with any protein in the
      database. We have also performed RT-PCR analysis with RNA extracted from human
      spermatozoa, utilizing various oligoprimers in different regions of the human
      progesterone genomic receptor. Results indicate the presence of transcripts for
      the complete genomic receptor. However, several previously published studies in
      the literature indicate the absence of expression of the genomic receptor in
      human spermatozoa. In this light posttranscriptional/posttraductional
      modifications of the receptor can be hypothesized. Interestingly, with primers
      amplifying in the DNA-binding domain of the progesterone receptor gene, we
      detected a higher molecular weight transcript when compared to the placenta.
      Further studies are needed to determine whether the sequences of the transcripts
      obtained by RT-PCR analysis of human sperm RNA match exactly with the human
      genomic receptor gene and to define the sequence of the higher molecular weight
      transcript detected in the DNA-binding region.

PMID- 11960629
TI  - Progestin membrane receptors involved in the meiotic maturation of teleost
      oocytes: a review with some new findings.
AB  - The endocrine control of oocyte maturation in fish has proven to be a valuable
      model for investigating rapid, nongenomic steroid actions at the cell surface.
      Considerable progress has been made over the last decade in identifying and
      characterizing progestin membrane receptors mediating these actions in fish, in
      understanding the hormonal regulation and physiological roles of these receptors
      in oocyte maturation, in elucidating the signal transduction pathways they
      activate, and in determining their nature. Recent advances on these topics are
      briefly reviewed. New data demonstrating the involvement of pertussis toxin
      sensitive inhibitory G-proteins in induction of oocyte maturation by the
      maturation-inducing steroid (MIS) in teleosts is also presented. In addition, the
      cloning strategy to isolate the MIS receptor gene from spotted seatrout ovaries
      and the characteristics of a novel gene and protein discovered by this approach
      are discussed. Current evidence suggests this G-protein-coupled receptor-like
      protein is the long sought after MIS receptor mediating meiotic maturation of
      teleost oocytes.

PMID- 11960630
TI  - Withdrawal properties of a neuroactive steroid: implications for GABA(A) receptor
      gene regulation in the brain and anxiety behavior.
AB  - Early work in the field established that the 5 alpha-reduced metabolite of
      progesterone 3 alpha-OH-5 alpha-pregnan-20-one (allopregnanolone or 3 alpha,5
      alpha-THP) is a potent positive modulator of the GABA(A) receptor (GABAR), the
      receptor mediating the effects of the primary inhibitory transmitter in the
      brain. This steroid acts in a manner similar to sedative drugs, such as the
      barbiturates, both in terms of potentiating GABA-induced inhibition in vitro and
      in behavioral assays, by reducing anxiety and seizure susceptibility. Because
      sedative compounds exhibit withdrawal properties that result in behavioral
      hyperexcitability, our laboratory has more recently investigated the effect of
      prolonged application and rapid removal (i.e. 'withdrawal') of this steroid,
      administered in vivo to female rats. Withdrawal from 3 alpha,5 alpha-THP produces
      a state of increased anxiety and lowered seizure threshold, similar to withdrawal
      from other GABA-modulatory drugs such as the benzodiazepines and alcohol. Hormone
      withdrawal also produced increases in the alpha 4-containing GABAR, an effect
      correlated with insensitivity of the GABAR to modulation by the benzodiazepine
      class of tranquilizers, as would normally occur under control conditions. In
      addition, changes in intrinsic channel properties, including a marked
      acceleration in the decay rate was also observed as a result of declining levels
      of 3 alpha,5 alpha-THP. Such a change would result in less inhibitory total
      current, and the resulting increase in neuronal excitability could then underlie
      the observed behavioral excitability following hormone withdrawal. These results
      suggest that actions of this steroid on a traditional transmitter receptor in the
      brain lead to alterations in GABAR subunit composition that result in changes in
      the intrinsic channel properties of the receptor and behavioral excitability.
      These results may have implications for endogenous fluctuations in this hormone
      which may accompany premenstrual dysphoric disorder.

PMID- 11960631
TI  - Rapid glucocorticoid effects on immune cells.
AB  - Apart from their classic genomic effects, it is well known that glucocorticoids
      also have rapid, nongenomically mediated effects. Three different mechanisms are
      currently under discussion as being responsible for these effects: (1) specific
      interaction with the cytosolic glucocorticoid receptor (cGCR), (2) nonspecific
      interactions with cellular membranes and (3) specific interactions with membrane
      bound glucocorticoid receptors (mGCR). With regard to the first mechanism, there
      is evidence that although the binding of glucocorticoids to the cGCR-associated
      multi-protein complex induces the further processes of the classic path, it also
      leads to a rapid intracellular signalling through other components of the complex
      (e.g. Src). For the second mechanism, a nonspecific interactive effect with
      cellular membranes through the intercalation of glucocorticoid molecules is being
      discussed, which primarily alters cellular functions by influencing cation
      transport via the plasma membrane and by increasing the proton leak of the
      mitochondria. With regard to the third, mGCR-mediated mechanism, the first
      evidence has now been found to suggest a physiological expression of membrane
      bound glucocorticoid receptors on human cells, whereas in humans this had
      previously only been demonstrated on lymphoma cells. The clinical importance and
      therapeutic relevance of these rapid glucocorticoid effects remains unclear at
      present, although effects on intracellular signalling, interferences with
      bioenergetically relevant cell functions and the induction of apoptosis via the
      mGCR are being discussed. This article gives a detailed presentation of the data
      available at present concerning rapid glucocorticoid effects on immune cells.

PMID- 11960632
TI  - Testosterone signaling in T cells and macrophages.
AB  - This review summarizes data about non-genomic actions of testosterone on murine
      malaria, T cells and macrophages produced by our group during the last 15 years.
      In C57BL/10 mice, testosterone induces a lethal outcome of blood stage infections
      with Plasmodium chabaudi which normally takes a self-healing course controlled by
      genes of the H-2 complex and the non-H-2 background. This suppressive effect of
      testosterone is mediated neither via the classic intracellular androgen receptor
      (AR) response nor, after conversion of testosterone to estradiol, via the
      estrogen receptor. Testosterone acts non-genomically, i.e. through surface
      receptors, on murine T cells and macrophages, which becomes evident as a rapid
      rise in the intracellular free Ca(2+) concentration ([Ca(2+)](i)). In T cells,
      this rise reflects predominantly influx of extracellular Ca(2+), while it is
      predominantly due to release of Ca(2+) from intracellular Ca(2+)-stores in
      macrophages. The testosterone-induced rise in [Ca(2+)](i) of both macrophages and
      T cells is not inhibited by the AR-blocker cyproterone, and it is also inducible
      by the plasma membrane impermeable ligand testosterone-BSA. The surface receptors
      initiate a transcription-independent signaling pathway of testosterone.
      Currently, we are trying to isolate testosterone surface receptors and to
      investigate a possible cross-talk of non-genomic testosterone signaling with
      other genotropic signaling pathways.

PMID- 11960633
TI  - Signal transduction mechanisms mediating rapid, nongenomic effects of cortisol on
      prolactin release.
AB  - While the mechanisms governing genomically mediated glucocorticoid actions are
      becoming increasingly understood, relatively little is known with regard to the
      cell signaling pathways that transduce rapid glucocorticoid actions. Studies of
      the cultured tilapia rostral pars distalis (RPD), a naturally segregated region
      of the fish pituitary gland that contains a 95-99% pure population of prolactin
      (PRL) cells and is easily dissected and maintained in a completely defined, serum
      free media, indicate that physiological concentrations of cortisol rapidly
      inhibit PRL release. The attenuative action of cortisol on PRL release occurs
      within 10-20 min, is insensitive to the protein synthesis inhibitor,
      cycloheximide, and mimicked by its membrane impermeable analog, cortisol-21
      hemisuccinate-conjugated bovine serum albumin (BSA). Cortisol and somatostatin, a
      peptide known to work through membrane receptors to inhibit PRL release, rapidly
      and reversibly reduces intracellular free Ca(2+) (Ca(i)(2+)), and inhibits
      45Ca(2+) influx and BAYK-8644 induced PRL release. Preliminary investigations
      show cortisol, but not somatostatin, suppresses phospholipase C (PLC) activity in
      PRL cell membrane preparations. In addition, cortisol and somatostatin reduce
      intracellular cAMP and membrane adenylyl cyclase activity. These findings
      indicate that the acute inhibitory effects of cortisol on PRL release occur
      through a nongenomic mechanism involving interactions with the plasma membrane
      and inhibition of both the Ca(2+) and cAMP signal transduction pathways. Cortisol
      may reduce Ca(i)(2+) by inhibiting influx through L-type voltage-gated channels
      and possibly release through a PLC/inositol triphosphate sensitive intracellular
      Ca(2+) pool. In addition, it is also likely the steroid inhibits adenylyl cyclase
      activity in events leading to reduced cAMP production and the subsequent release
      of PRL.

PMID- 11960635
TI  - Expression and regulation of interleukin-1 receptors in the brain. Role in
      cytokines-induced sickness behavior.
AB  - Sickness behavior refers to the coordinated set of behavior changes that develop
      in sick individuals during the course of an infection. At the molecular level,
      these changes are due to the effects of proinflammatory cytokines as interleukin
      1 on the brain. The purpose of this article is not to review the entire field of
      cytokines and behavior, but rather to address the role of interleukin-1 receptors
      (IL-1Rs) in sickness behavior. We briefly describe the notion of sickness
      behavior and present the distribution of IL-1Rs in the central nervous system of
      the human, mouse and rat. We then bring arguments in favor of the functionality
      of the various subtypes of receptors and evaluate the nature of the signaling
      pathways activated by brain IL-1Rs to initiate central modifications leading to
      symptoms of sickness. Finally, modulation of IL-1 action on its receptor by
      various opposing factors including glucocorticoids and anti-inflammatory
      cytokines is discussed.

PMID- 11960637
TI  - Inhibition of NF-kappaB activity by plasmid expressed alphaMSH peptide.
AB  - Alpha-Melanocyte Stimulating Hormone (alphaMSH) is a neuroimmunomodulatory
      peptide with remarkable anti-inflammatory properties. Daily or twice daily
      administration of the peptide reduces the symptoms of several inflammatory animal
      disease models and the peptide has demonstrated safety in human trials.
      Unfortunately, the pharmacokinetics of peptide delivery are not favorable from
      the pharmaceutical perspective. For this reason, plasmid-based vectors were
      created that constitutively express the immunomodulatory peptide. The fusion
      constructs encode the 13 amino acids of alphaMSH in frame with the first domain
      of serum albumin, separated by a linker and furin cleavage sites. The fusion
      proteins were expressed and processed in human fetal kidney (293) cells.
      Supernatant from B16/F10 cells transfected with the constructs stimulated
      secretion of melanin from melanocytes. Furthermore, transfected cytoskeletal
      muscle (Sol8) cells secreted bioactive alphaMSH that reduced NF-kappaB-mediated
      transcriptional activation of a luciferase reporter gene. The activity of these
      vectors provides tools and the impetus for testing the constructs in several
      animal models of chronic inflammation.

PMID- 11960636
TI  - Avirulent Semliki Forest virus replication and pathology in the central nervous
      system is enhanced in IL-12-defective and reduced in IL-4-defective mice: a role
      for Th1 cells in the protective immunity.
AB  - Experimental infection of mice with avirulent Semliki Forest virus (SFV) has been
      used as a model of demyelinating disease in humans. A number of studies have
      shown that T cells may be important for mediating demyelination, but the role of
      T cells is still, unclear. Here, we show that neuronal necrosis, but not
      demyelination, was more severe in interleukin (IL)-12-defective mice compared
      with wild-type mice and this correlated with higher virus titers in the brain. In
      contrast, the severity of demyelination and neuronal depletion was reduced in IL
      4-defective mice and this correlated with reduced brain virus titers and enhanced
      SFV-specific IFN-gamma production. The findings indicate that type 1 T cells play
      a role in the control of SFV replication but not directly in SFV-induced
      pathology in the CNS.

PMID- 11960638
TI  - Increased expression of pro-inflammatory cytokines and lack of up-regulation of
      anti-inflammatory cytokines in early distemper CNS lesions.
AB  - To investigate the pathogenesis of early lesions in canine distemper virus (CDV)
      leukoencephalomyelitis, the expressions of pro- and anti-inflammatory cytokines
      such as interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, tumor necrosis
      factor (TNF)-alpha, interferon (IFN)-gamma and transforming growth factor (TGF)
      beta and the housekeeping genes beta-actin and GAPDH were studied using semi
      quantitative RT-PCR. Relative cytokine values were related to the degree of CDV
      infection, MHC class II expression and infiltration of CD4-, CD8- and CD3epsilon
      positive lymphocytes. Actin up-regulation, in contrast to GAPDH, was influenced
      by CDV infection and therefore could not be used as an internal standard to study
      cytokine expression. In early CDV infection of the cerebellum, either no
      detectable lesions or mild infiltration of CD8 positive cells or demyelination
      and up-regulation of MHC class II antigen were observed. IL-6, -8, -12 and TNF
      alpha transcripts were found in 94%, 94%, 78% and 56% of distemper dogs,
      respectively, compared to 17%, 33%, 0% and 0% in controls, whereas IL-1beta, -2
      and IFN-gamma were not detectable in any of the studied cerebella. Conversely, IL
      10 and TGF-beta transcripts were present in 83% and 100% of the investigated
      cerebella of distemper dogs and controls. Relative RT-PCR results, expressed as
      %GAPDH, revealed a significant up-regulation of IL-6, -8, -12 and TNF-alpha mRNA
      in distemper dogs; whereas IL-10 and TGF-beta showed only a weak and not
      significantly increased expression following infection. Relative pro-inflammatory
      cytokine expression values were highest following CDV infection, indicating that
      the virus itself directly triggered the up-regulation of the pro-inflammatory
      cytokines. Succeeding changes, such as lymphocyte infiltration, MHC class II up
      regulation and demyelination resulted only in a minor additional increase in
      cytokine expression, implying a secondary or by-stander mechanism of cytokine
      activation by these changes. Disease initiation and progression in early
      distemper leukoencephalomyelitis seemed to be due to a lacking or inappropriate
      response of the anti-inflammatory cytokines in the presence of a vigorous up
      regulation of pro-inflammatory cytokines.

PMID- 11960639
TI  - Regulation of class I MHC expression in skeletal muscle: deleterious effect of
      aberrant expression on myogenesis.
AB  - Aberrant expression of class I major histocompatibility complex (MHC) occurs on
      myofibers in inflammatory myopathies. The mechanisms responsible for such
      expression are unknown. Here we show that class I MHC expression is
      developmentally regulated during muscle regeneration with significant levels only
      in myoblasts. Injection of gamma-IFN plasmid leads to muscle inflammation,
      induction of class I MHC in regenerating, but not mature myofibers, and
      attenuation of regeneration. Gene transfer of class I MHC in vivo and in vitro
      also attenuates muscle differentiation. Thus, cytokines may contribute to the
      pathogenesis of inflammatory myopathies by upregulating class I MHC and leading
      to deleterious effects on muscle repair.

PMID- 11960640
TI  - Role of IL-5 during primary and secondary immune response to acetylcholine
      receptor.
AB  - To analyze the role of the Th2 cytokine interleukin-5 (IL-5) in experimental
      autoimmune myasthenia gravis (EAMG) pathogenesis, we induced clinical EAMG in
      C57BL/6 and IL-5 gene-knockout (KO) mice in the C57BL/6 background. IL-5 KO mice
      had a significantly reduced incidence and severity of EAMG. Despite their
      increased resistance to EAMG, IL-5 KO mice displayed intact secondary antibody
      and lymphoproliferative responses to acetylcholine receptor (AChR) after
      immunization with this molecule. However, the relative resistance of IL-5 KO mice
      was associated with a reduced primary lymphocyte response to AChR, and reduced C3
      levels in muscle extracts compared to those in C57BL/6 mice.

PMID- 11960641
TI  - Mice deficient in fractalkine are less susceptible to cerebral ischemia
      reperfusion injury.
AB  - Fractalkine (FKN), also known as neurotactin, is a CX(3)C chemokine that exists
      in both secreted and neuronal membrane-bound forms and is upregulated during
      brain inflammation. There is accumulating evidence that FKN induces chemotaxis by
      binding to its receptor CX(3)CR1 on leukocytes and microglia. We generated FKN
      deficient mice to study the role of FKN in postischemic brain injury. After
      transient focal cerebral ischemia, FKN-deficient mice had a 28% reduction in
      infarction size and lower mortality rate, when compared to wild-type littermates.
      The findings of this study indicate a possible role for FKN in augmenting
      postischemic injury and mortality after transient focal cerebral ischemia.

PMID- 11960642
TI  - Cytokines regulate alpha(1)-adrenergic receptor mRNA expression in human
      monocytic cells and endothelial cells.
AB  - The family of adrenergic receptors (AR) plays a central role in regulation of the
      activity of many organ systems. Consequently, regulated expression of the various
      subtypes of AR is an important mechanism in maintaining homeostasis. Previously,
      we have shown that alpha(1)-AR triggering of peripheral blood mononuclear cells
      from patients with juvenile chronic arthritis results in increased IL-6
      production. In contrast, alpha(1)-AR agonists do not alter cytokine production by
      cells of healthy individuals. The aim of the present study was to investigate
      whether pro-inflammatory cytokines can regulate the expression of mRNA encoding
      AR of the alpha(1)-family. We show that human THP-1 monocytic cells express mRNA
      encoding of two of the three cloned subtypes of alpha(1)-AR: alpha(1b)-AR and
      alpha(1d)-AR mRNA. The cytokines TNF-alpha and IL-1beta decrease level of mRNA
      for alpha(1d)-AR in THP-1 monocytic cells. In contrast, alpha(1b)-AR mRNA levels
      are not affected by these two cytokines. Interestingly, IL-1beta and TNF-alpha
      induce the expression of alpha(1a)-AR mRNA in THP-1 monocytic cells. In human
      umbilical vein endothelial cells (HUVEC), IL-1beta and TNF-alpha decrease both
      alpha(1b)-AR and alpha(1d)-AR mRNA levels in HUVEC. alpha(1a)-AR mRNA is not
      detectable in HUVEC.IL-6 and IL-8, two other pro-inflammatory cytokines tested in
      this study, do not change alpha(1)-AR subtype levels in HUVEC or monocytic cells.
      Our data demonstrate that TNF-alpha and IL-1beta can regulate expression of
      alpha(1)-AR mRNA and that cytokine regulation of alpha(1)-AR expression is
      subtype- and tissue-specific.

PMID- 11960643
TI  - Immunoregulation of IL-6 secretion by endogenous and exogenous adenosine and by
      exogenous purinergic agonists in splenic tissue slices.
AB  - In recent years, the role of norepinephrine, opioids, and neuropeptide Y for
      sympathetic regulation of murine spleen cells has been characterised. In this
      study, we describe the role of exogenous and endogenous adenosine and exogenous
      P2X(1) and P2Y(1) agonists for spontaneous splenic IL-6 secretion from spleen
      slices. The P2X(1) agonist beta,gamma-methylene ATP inhibited IL-6 secretion at
      10(-5) M, whereas the P2Y(1) agonist 2-methylthio ATP increased IL-6 secretion at
      10(-6) to 10(-8) M. Furthermore, adenosine (at 5 x 10(-8), 10(-7), 5 x 10(-7) M)
      inhibited IL-6 secretion via A1 adenosine receptors, whereas an A2(A) adenosine
      receptor agonist increased IL-6 secretion in the presence of 10(-7) M cortisol.
      To determine the effects of endogenous adenosine, electrical field stimulation
      was applied in order to release endogenous ATP, which yields adenosine after
      conversion from ATP. Electrical field stimulation markedly reduced IL-6
      secretion, which was attenuated by the A1 antagonist DPCPX but not by the A2
      antagonist 8-(3-Chlorostyryl)caffeine. Thus, via A1 adenosine receptors,
      adenosine was found to be a strong inhibitor of splenic IL-6 secretion. This
      study further expands our earlier description of the complexity of the local
      dialogue of sympathetic nerves and macrophages in lymphoid organs.

PMID- 11960644
TI  - The differential role of spinal MHC class II and cellular adhesion molecules in
      peripheral inflammatory versus neuropathic pain in rodents.
AB  - The present study was designed to determine the role of central expression of
      immunoregulatory molecules in the development and maintenance of allodynia
      following a peripheral inflammatory insult or nerve transection. Differential
      spinal expression of major histocompatibility complex (MHC) class II, platelet
      endothelial cellular adhesion molecule (PECAM), intercellular adhesion molecule
      (ICAM) and CD4 was observed in the two injury models. Intraplantar zymosan
      produced transient allodynia and only PECAM and ICAM immunoreactivity. In
      contrast, persistent mechanical allodynia and enhanced spinal PECAM, ICAM, MHC
      class II and CD4 immunoreactivity was observed following peripheral nerve
      transection. MHC class II knockout mice exhibited attenuated allodynia following
      spinal nerve transection as compared to wild-type control mice. These findings
      suggest that central neuroimmune activation may contribute to the maintenance of
      neuropathic pain following peripheral L5 spinal nerve transection but not
      following a peripheral inflammatory insult.

PMID- 11960645
TI  - Sympathetic nervous system plays a major role in acute cold/restraint stress
      inhibition of host resistance to Listeria monocytogenes.
AB  - BALB/c mice exposed to acute cold/restraint stress (ACRS) had significantly lower
      host resistance to Listeria monocytogenes (LM) than controls. The stress hormones
      corticosterone (CORT) and norepinephrine (NE), which are known to modulate immune
      responses, were evaluated as the cause of the decline in immune defense. The
      involvement of CORT and NE was investigated by pretreating mice with the CORT
      synthesis inhibitor metyrapone and the chemical sympathectomy drug 6
      hydroxydopamine (6-OHDA), respectively. LM burdens in spleen and liver were
      determined three days post-infection. 6-OHDA significantly decreased the LM
      burden in both control and stressed animals. 6-OHDA also completely blocked the
      stress effects observed in spleens while only partially affecting the liver. The
      6-OHDA-uptake inhibitor desipramine aided confirmation that peripheral
      sympathetic adrenergic nerves and NE depletion, rather than the direct action of
      6-OHDA, were responsible for the decreased susceptibility to LM. The results
      suggest that the peripheral sympathetic nervous system (SNS) postganglionic
      neurotransmitter NE plays a major role in LM host resistance and has significant
      tissue-dependent effects after ACRS. In contrast, metyrapone-treated animals had
      further decreased host resistance to LM, suggesting a potential protective effect
      of CORT after ACRS. Altogether, the results suggest that stress hormones play an
      important role in stress-modulated host resistance and that NE is the major
      hormone involved in ACRS-induced suppression of host resistance.

PMID- 11960646
TI  - hNT neurons express an immunosuppressive protein that blocks T-lymphocyte
      proliferation and interleukin-2 production.
AB  - Ntera2/D1 cells had an A1 B8 Bw6 Cw7 DR3 DR52 major histocompatibility complex
      (MHC) genotype. Its neuronal derivative, hNT neurons, expressed A1 B8 Bw6 MHC
      class I molecules, but did not activate, and its hNT supernatant suppressed
      allogeneic mixed lymphocyte cultures (MLC) >98% (p<0.01), phytohemagglutinin
      (PHA)-activated T-cell proliferation >87% (p<0.01), even 48 h after stimulation,
      suppressed phorbol 12-myristate 13-acetate (PMA)/ionomycin-induced T-cell
      proliferation >99% (p<0.001), and reduced interleukin-2 (IL-2) production
      (p<0.01), while maintaining T cells in a quiescent G(0)/G(1) state without
      lowering their viability. This immunosuppressive activity was attributed to a 40
      100-kDa anionic hNT protein with an isoelectric point of 4.8.

PMID- 11960647
TI  - Pathological and regulatory effects of anti-myelin antibodies in experimental
      allergic encephalomyelitis in mice.
AB  - Neurological deficit in experimental allergic encephalomyelitis (EAE) and
      multiple sclerosis (MS) is probably a consequence of synergy between T and B cell
      responses to CNS antigens. During the demyelinating phase of chronic relapsing
      EAE in ABH mice, anti-myelin oligodendrocyte glycoprotein (MOG) responses were
      increased compared to the inflammatory acute phase, but such levels did not
      correlate with the severity of clinical disease. The pathogenicity of antibodies
      (Ab) to MOG, myelin basic protein (MBP), proteolipid protein (PLP) and
      galactocerebroside (GalC) was investigated in vivo following injection at the
      onset of EAE. An IgG2a monoclonal Ab (mAb), clone Z12, directed to MOG augmented
      clinical disease and demyelination in ABH and C57BL/6 mice, but not MOG knock-out
      mice. No effect was observed with F(ab(2))' fragments of Z12 or with the anti-MOG
      IgG1 mAbs, clones Y10 or 8-18C5. Cobra venom factor partially reduced the
      augmenting effect of mAb Z12 suggesting a role for complement. The pathogenic
      effect of anti-myelin Abs was not restricted to MOG since an anti-GalC mAb
      exacerbated inflammation in the CNS while an MBP mAb (clone 22) reduced clinical
      disease. Taken together, these data provide further evidence that myelin-reactive
      Abs generated during autoimmune neurological disease may play an important role
      not only in the pathogenesis of disease but also the regulation of myelin
      targeted autoimmune disease.

PMID- 11960648
TI  - Stimulation with phytohaemagglutinin induces the synthesis of catecholamines in
      human peripheral blood mononuclear cells: role of protein kinase C and
      contribution of intracellular calcium.
AB  - Although it is now established that immunocompetent cells produce catecholamines
      (CA), which in turn may act as autocrine/paracrine mediators, little is known
      about the mechanisms regulating CA production in these cells. In the present
      study, evidence is provided that stimulation of human cultured peripheral blood
      mononuclear cells (PBMCs) with phytohaemagglutinin (PHA) induces the expression
      of tyrosine hydroxylase (TH) mRNA and subsequently increases intracellular CA
      levels through protein kinase C (PKC) activation and the contribution of
      intracellular Ca(++)-dependent mechanisms. Increased production of CA in PHA
      stimulated PBMCs suggests a preferential involvement of catecholaminergic
      pathways in the functional modulation of activated cells. These findings may help
      to better define the role of immunocompetent cell-derived CA in the neuroimmune
      network.

PMID- 11960649
TI  - IL-18 is linked to raised IFN-gamma in multiple sclerosis and is induced by
      activated CD4(+) T cells via CD40-CD40 ligand interactions.
AB  - We investigated T cell receptor induced IL-18 secretion, the cellular and
      molecular mechanisms associated with the induction of IL-18 and the role of IL-18
      in IFN-gamma production in the different stages of multiple sclerosis (MS). We
      found that anti-CD3/CD28 induced IL-18 production by peripheral blood mononuclear
      cells was increased in both relapsing-remitting and secondary progressive MS. In
      controls and relapsing-remitting MS neutralizing anti-IL-12 and anti-IL-18 alone
      equally suppressed IFN-gamma production whereas in progressive MS, maximum
      suppression of IFN-gamma was only observed when neutralizing anti-IL-12 and anti
      IL-18 were given together, suggesting that in progressive MS, IL-12 and IL-18
      function in a non-linked manner to induce IFN-gamma. Elevated IL-18 production in
      MS was dependent on the interaction of antigen presenting cells with activated
      CD4(+) T cells via CD40-CD40 ligand and the levels of IL-18 correlated with
      disease duration in secondary progressive MS. These results demonstrated that IL
      18 has an important role in augmenting Th-1 type immune responses in MS and may
      be involved in immune changes that occur when patients enter the progressive
      stage.

PMID- 11960650
TI  - Chromosome 7q21-22 and multiple sclerosis: evidence for a genetic susceptibility
      effect in vicinity to the protachykinin-1 gene.
AB  - Chromosome 7q21-22 and, in particular, the region surrounding D7S554 emerged from
      the recent American genome screen in multiple sclerosis (MS) as the most
      promising region genome-wide for harboring a disease susceptibility gene. We
      tested association between D7S554 and MS in 217 Sardinian trio MS families by the
      transmission disequilibrium test (TDT), and in a Northern Irish case-control
      study comprising 542 individuals. In both populations, we found evidence for
      significant allelic association (P(c)=0.04 and P(c)=0.0002, respectively). In a
      second stage, we analysed five microsatellite markers in a 4 megabase interval on
      chromosome 7q21-22 in the same set of Sardinian families. Parental transmission
      of a single allele of one of these markers, i.e. D7S3126, was significantly
      distorted (P(c)=0.008). D7S554 and D7S3126 are located at distances of,
      respectively, 40 and 81 kb 5' from the startcodon of the protachykinin-1 gene
      (TAC1), and occur in strong linkage disequilibrium (P<10(-7)). Our study
      indicates that the previous finding of linkage with D7S554 refers possibly to the
      presence of an MS susceptibility effect in vicinity to TAC1. In addition, a
      second independent association was uncovered between a microsatellite
      polymorphism in the plasminogen activator inhibitor-1 gene, i.e. D7S477, and MS.
      Overall, the analysis presented here may contribute to the increasingly refined
      genomic map of MS and underscores the requirement for a further high-resolution
      screening of chromosome 7q21-22.

PMID- 11960651
TI  - Immunological disturbances in the central nervous system linked to MRI findings
      in multiple sclerosis.
AB  - To clarify immunological disturbances in the central nervous system (CNS) in
      multiple sclerosis (MS) by linking to magnetic resonance imaging (MRI) findings,
      22 patients with relapsing remitting MS were studied. Cerebrospinal fluid (CSF)
      samples were analyzed during a total of 27 independent MS stages (20 active, 7
      inactive) on 25 occasions during which gadolinium (Gd)-enhanced MRI scans were
      performed. The number of Gd-enhanced lesions was significantly correlated with
      CSF cell counts, as well as the number of CD4(+)CD29(+) helper inducer and IL-2
      receptor (CD25)-positive activated helper T cells. In contrast, T(2) lesion load
      in the brain showed a trend of association with elevated IgG index.

PMID- 11960652
TI  - The expression of pro- and anti-apoptosis Bcl-2 family proteins in lymphocytes
      from patients with multiple sclerosis.
AB  - Programmed cell death (apoptosis) is critical for the normal development and
      homeostasis of the immune system. There is increasing evidence that
      dysregulations of apoptotic pathways are associated with autoimmune disease,
      including multiple sclerosis (MS). Cellular commitment to apoptosis is partly
      regulated by the Bcl-2 family proteins, which includes the death antagonists Bcl
      2 and Bcl-X(L), and death agonists Bax and Bad. Since the role of these proteins
      in the pathogenesis of MS is currently unknown, we analyzed their expression
      profile in peripheral and intrathecal lymphocytes from MS patients and
      appropriate controls. We observed a significant reduction in the expression
      ratios of pro-apoptotic to anti-apoptotic Bcl-2 members in both peripheral and
      intrathecal lymphocytes from MS patients when compared to corresponding ratios in
      patients with inflammatory or noninflammatory neurologic controls, or healthy
      individuals. The relative coexpression ratios of these pro- and anti-apoptotic
      Bcl-2 family proteins in MS were more significant than the expression of
      individual members. The low cellular expression ratios of pro-apoptotic proteins
      in MS were confirmed in vitro activated T lymphocytes. Cellular expression of Bcl
      2, Bcl-X(L), Bax or Bad in MS patients was independent of the expression of other
      apoptotic regulatory molecules, such as Fas receptor protein or FLIP. Our
      findings suggest that the abnormal expression patterns of Bcl-2 family proteins
      in MS may promote apoptotic resistance of potentially pathogenic, autoreactive
      lymphocytes, and may allow for continuing cellular proliferation and tissue
      destruction within the central nervous system.

PMID- 11960653
TI  - A sensitive flow cytometry method for anti-GM1 antibodies detection.
AB  - High-affinity anti-GM1 antibodies are frequently described in several nervous
      system diseases, mainly in multifocal motor neuropathy (MMN) and some acute
      neuropathies. These antibodies are currently detected using enzyme-linked
      immunosorbent assay (ELISA) and immuno-thin-layer-chromatography (immuno-TLC)
      methods. We report in this article a new method based on the incorporation of
      exogenous GM1 in a selected cell line to detect anti-GM1 antibodies using flow
      cytometry (FC). This method is evaluated on 80 sera from normal blood donors
      (NBD) and patients suffering various nervous system diseases. It appears to be as
      sensitive as our method ELISA for the diagnosis of some motor neuron syndromes.

PMID- 11960654
TI  - Altered expression of glutamate transporters in experimental autoimmune
      encephalomyelitis.
AB  - Amelioration of experimental autoimmune encephalomyelitis (EAE) by blockade of
      the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor, 2,3
      dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), has been recently
      demonstrated [Nat. Med. 6 (2000) 67; Nat. Med. 6 (2000) 62]. However, the
      mechanisms underlying regulation of the extracellular glutamate concentration in
      EAE are unclear. To address this, we examined the expression of three distinct
      Na(+)-dependent glutamate transporters (GLT-1, GLAST and EAAC1) in the spinal
      cord of the Lewis rat EAE. EAE induced a dramatic increase in EAAC1 protein and
      mRNA levels, which corresponded closely with the course of neurological symptoms.
      In contrast, the levels of GLT-1 and GLAST protein were down-regulated in the
      spinal cord at the peak of disease symptoms, and no recovery was observed after
      remission. Furthermore, these changes in GLT-1, GLAST and EAAC1 expression were
      suppressed by treatment with NBQX. These results suggest that AMPA receptor
      activation precedes the altered expression of glutamate transporters, and that
      the dysregulation of extracellular glutamate concentration might play a critical
      role in pathological changes and neuronal dysfunction in EAE.

PMID- 11960655
TI  - Increased sialyl Lewis(x) antigen-positive cells mediated by HTLV-1 infection in
      peripheral blood CD4(+) T lymphocytes in patients with HTLV-1-associated
      myelopathy.
AB  - Sialyl Lewis(x) antigen-positive (sLe(x+)) cells play an important role in the
      first step of transmigration of T lymphocytes through vascular endothelial cells
      into tissues. We compared the proportion of sLe(x+) cells in peripheral blood
      CD4(+) T lymphocytes between patients with HTLV-1-associated myelopathy (HAM) and
      control patients, by using flow cytometry. The percentage of sLe(x+) cells in
      peripheral blood CD4(+) T lymphocytes was significantly higher in HAM patients
      compared to control patients. Interferon-gamma (IFN-gamma), but not interleukin-4
      (IL-4), production by the sLe(x+) cell population of peripheral blood CD4(+) T
      lymphocytes was significantly higher in HAM patients than in control patients. In
      addition, comparison of the HTLV-1 proviral load between sLe(x+) and sLe(x-)
      cells in peripheral blood CD4(+) T lymphocytes of HAM patients showed that the
      HTLV-1 proviral load was significantly higher (two- to eight-fold), concomitant
      with enhanced IFN-gamma production, in the sLe(x+) than in the sLe(x-) cell
      population. Our findings indicate that the sLe(x+) cell population, which has
      features of activated Th1 cells with up-regulated expression of E- and P-selectin
      ligands mediated by HTLV-1 infection, is increased in peripheral blood CD4(+) T
      lymphocytes in HAM patients, suggesting their involvement in transmigration of
      peripheral T lymphocytes from the peripheral blood into tissues.

PMID- 11960656
TI  - Thymic myoid cells and germinal center formation in myasthenia gravis; possible
      roles in pathogenesis.
AB  - In early-onset myasthenia gravis (EOMG), the thymus usually shows medullary lymph
      node-type infiltrates, rearranged bands of hyperplastic epithelium and focal
      fenestrations in the intervening laminin borders. This resemblance to autoimmune
      target organs may reflect autoantigen expression by rare thymic myoid cells, long
      ago implicated circumstantially as agents provocateurs. In this quantitative
      study, they were frequently seen at the laminin fenestrations; if so, germinal
      centers (GC) were significantly commoner nearby, our most EOMG-specific finding
      (not seen in a distinct MG patient subset). As autoantibodies became detectable,
      myoid cell involvement apparently progressed. Our unifying hypothesis--that an
      early autoantibody attack on myoid cells provokes local GC formation--helps to
      resolve many puzzles.

PMID- 11960657
TI  - Cerebrospinal fluid levels of nitric oxide metabolites predict response to
      methylprednisolone treatment in multiple sclerosis and optic neuritis.
AB  - The role of nitric oxide (NO) in multiple sclerosis (MS) is not clear. We found
      increased cerebrospinal fluid concentrations of the NO degradation products
      nitrate (NO(x)) in clinically definite MS but not in clinically isolated
      syndromes. High CSF concentrations of NO(x) correlated with long attack duration.
      Patients carrying the truncated CC chemokine receptor allele CCR5 Delta32 had
      lower serum concentration of NO(x) at later attack stages. NO(x) concentrations
      did not change after methylprednisolone treatment but high concentrations were
      associated with more pronounced treatment responses. These findings suggest an
      association of high CSF levels of NO(x) with more severe disease activity in
      relapsing-remitting MS.

PMID- 11960658
TI  - [Total knee arthroplasty: reproducibility of gait speed].
AB  - OBJECTIVE: To calculate the inter-session (test-retest) and inter-observers'
      reproducibility of the maximal gait speed measured in patients recently operated
      for osteoarthritis with a total knee arthroplasty. METHODS: Evaluation of the
      maximal gait speed in 20 patients [t72 +/- 6.5 years] on a 10-meter track by two
      observers using a manual stopwatch and by an automatic photoelectric stopwatch.
      The maximal gait speed was measured from three trials in two conditions, with and
      without crutches, with 1 day of interval at the third and the fourth post-surgery
      week. RESULTS: The inter-session reproducibility (1-day test-retest) is 0.91
      [intraclass correlation coefficient] with crutches and 0.9 without crutches at
      the third post-surgery week, and 0.96 and 0.94 at the fourth post-surgery week
      with and without crutches respectively. The inter-observers' reproducibility is
      0.9 to 0.99. CONCLUSION: When a standardized protocol is used, the
      reproducibility of maximal gait speed measurements is excellent. These tests
      evaluate easily and objectively the maximal gait speed in patients recently
      operated with a total knee arthroplasty.

PMID- 11960659
TI  - [Quality of life of a population of 54 ambulatory children with cerebral palsy. A
      cross-sectional study].
AB  - To evaluate the impact of handicap on quality of life in children with cerebral
      palsy and living in family. METHOD: A descriptive study by investigation was
      conducted in children with cerebral palsy, with the ability to walk, from 4 to 12
      years of age, and in their family. Quality of life was evaluated with the AUQUEI
      questionnaire. Another questionnaire was given to the parents to collect the
      different variables, which could influence quality of life of the child. RESULTS:
      The mean age was 9 years. Associations between the studied variables and the
      quality of life were observed for motor function, number of siblings and the
      quantity of hours of reeducation given by the family. Parents evaluated their
      quality of life on the visual scale at 72.23 mm (95CI: 51.60-92.84). There was no
      correlation between the assessment of quality of life of parents and children.
      DISCUSSION-CONCLUSION: The better the child's motor function the less satisfied
      he was. This result shows the poor correlation between quality of life and
      general condition, impairment or disability. The greater the number of children
      in the family the less satisfied the child was within the family and the more
      satisfied the child was at school. A handicapped child has perhaps a more
      difficult place in the close family and an easier time in a school where the
      environment is more neutral. The more time that is devoted by the family to
      reeducation the less the child is satisfied. Quality of life seems to be
      influenced negatively by the demands of physical therapy, which do not correspond
      to the reality of the abilities of the child.

PMID- 11960660
TI  - [Efficacy at six months of the botulinum toxin A in the post-stroke lower limb's
      muscular overactivity].
AB  - OBJECTIVE: Post-stroke hemiplegic patients are often disabled by a muscular
      overactivity of the lower limb which can be treated by botulinum toxin A (BTX).
      The aim of this study was to assess the length of this efficiency as expressed by
      the patient. MATERIAL AND METHOD: The study was conducted among consecutive
      patients with post-stroke hemiplegia, disabled by a distal muscular overactivity
      of the lower limb. The injection of BTX (Botox Allergan) was given under
      electrostimulation guidance. Efficiency was assessed by the patient at 1, 3 and 6
      months, by means of a three-point scale (absent, real but not enough, very good),
      on the basis of individual objectives previously defined after the precise
      description of the symptoms, their type of triggering and their functional
      impact. RESULTS: Fifty-seven sessions were conducted in 36 patients. At 1 month,
      81% of the sessions were efficient, 39% with very good results. At 6 months, 57%
      of the sessions were still efficient with 25% of very good results. The best
      results were observed on the permanent extension of the great toe: the efficiency
      remained very good at 6 months for 47% of the sessions. CONCLUSION: Having been
      assessed by the patients on the basis of individual objectives, the good result
      of the treatment by BTX can persist for more than 6 months. This assessment is
      partly subjective but is, in clinical use, the main basis for the treatment
      discussion.

PMID- 11960661
TI  - [Portable ultrasonographic device and bladder dysfunction management in stroke
      patients].
AB  - OBJECTIVE: To determine the usefulness of a portable ultrasonographic device in
      the management and rehabilitation of stroke patients' bladder voiding impairment
      in the early stage and to propose a well-fitted screening protocol. MATERIAL AND
      METHOD: A prospective observational study of 33 inpatients admitted into our
      stroke rehabilitation program. A urinary elimination assessment protocol defines
      the criteria of intermittent catheterization. The determination of bladder volume
      was performed with a Bladderscan BVI 3000 portable ultrasonographic device.
      RESULTS: Urinary retention was present in ten of the 33 patients at admission,
      who were started on one or many intermittent catheterizations. Retention was
      resolved for seven of them at discharge. The portable ultrasonographic device
      allows a very accurate bladder volume assessment, especially useful in at-risk
      patients: those with cognitive impairments, diabetes mellitus, and prestroke
      urinary pathology. A new version of our first screening protocol increases the
      ability to detect patients with true urinary retention. Results are discussed
      according to the literature data. CONCLUSION: The portable ultrasonographic
      device is a simple and noninvasive tool, useful for diagnosis, follow-up and
      therapy guidance of urinary retention after stroke. An adapted protocol is
      proposed in order to assess and rehabilitate this trouble. The goal is to avoid
      long-term catheterization and its linked infectious risk.

PMID- 11960662
TI  - Active conformation of some arylpiperazine postsynaptic 5-HT(1A) receptor
      antagonists.
AB  - The synthesis and pharmacological properties of novel conformationally restricted
      arylpiperazine (2b-4b) or 1,2,3,4-tetrahydroisoquinoline (5b and 6b) derivatives
      of the known, flexible 5-HT(1A) receptor ligands 2a-6a (K(i)=0.95-7 nM) with
      different intrinsic activities are reported. Replacement of a tetramethylene
      chain with a 1e,4e-disubstituted cyclohexane ring in the structure of flexible
      ligands resulted in insignificant diminution of the 5-HT(1A) receptor affinity in
      the case of 2b-4b (K(i)=15-52 nM), whereas derivatives 5b and 6b were practically
      inactive (K(i)>1354 nM). The results of in vivo behavioural tests showed that 2a
      and 3a acted as postsynaptic 5-HT(1A) receptor partial agonists. Like the
      flexible 4a, the new rigid compounds 2b-4b showed features of postsynaptic 5
      HT(1A) receptor antagonists. Since all possible conformations of the constrained
      compounds belong to an extended family--as indicated by molecular modelling
      studies--our hypothesis that such conformations are responsible for the blockade
      of postsynaptic 5-HT(1A) receptors has been confirmed. Determination of regions
      explored by terminal amide, or imide and hydrocarbon groups of the restricted
      compounds as well as the results of in vitro and in vivo studies allowed us to
      discuss the bioactive conformations of flexible ligands.

PMID- 11960663
TI  - Synthesis, molecular structure and anticancer activity of 1-allyl-3-amino-2-(4
      chloro-2-mercaptobenzenesulphonyl)guanidine derivatives.
AB  - A series of 3-allylamino-6-chloro-7-R-1,1-dioxo-1,4,2-benzodithiazines (2a-e) was
      obtained by the reaction of 6-chloro-3-methylthio-1,4,2-benzodithiazine-1,1
      dioxides (1a-e) with allylamine. Selective hydrazinolysis of the
      allylaminobenzodithiazines (2a-e) gave the appropriate 1-allyl-3-amino-2-(4
      chloro-2-mercaptobenzenesulphonyl)guanidines (3a-e) in good yields. The reaction
      of 3a with dimethylsulphate under alkaline conditions provided the methylthio
      derivative 4. The structures of these compounds were confirmed on the basis of
      elemental analysis, spectral data (IR, 1H- and 13C-NMR) and X-ray analysis.
      Screening data indicated that the compounds 3a and 3d exhibited significant in
      vitro activities against numerous human tumour cell lines, whereas compounds 3b
      and 3c showed a moderate activity.

PMID- 11960664
TI  - Structure-based design of nitrosoureas containing tyrosine derivatives as
      potential antimelanoma agents.
AB  - Two new nitrosoureas (TNUs), containing tyrosine derivatives as carriers of
      nitrosourea cytotoxic group have been synthesised. The physicochemical properties
      such as half-life time (tau(0.5)), alkylating and carbamoylating activities were
      determined. The nitrosoureas showed a higher inhibiting effect on the DOPA
      oxidase activity of mushroom tyrosinase than that of the antitumour drug N'
      cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU). In vitro cytotoxic
      effects of newly synthesised tyrosine containing nitrosoureas have been studied
      and compared to those of CCNU. A higher cytotoxicity to B16 melanoma cells than
      to YAC-1 and to lymphocytes was demonstrated for the tyrosine containing
      nitrosoureas in comparison with CCNU. Based on the results presented, we accept
      that a new trend for synthesis of more selective and less toxic nitrosourea
      derivatives as potential antimelanomic drugs might be developed.

PMID- 11960665
TI  - Synthesis, cytotoxic activities and proposed mode of binding of a series of
      bis([(9-oxo-9,10-dihydroacridine-4-carbonyl)amino]alkyl) alkylamines.
AB  - A series of bis([(9-oxo-9,10-dihydroacridine-4-carbonyl)amino]alkyl) alkylamines
      have been prepared and their antiproliferative properties have been tested
      against HT-29 cell lines. Compounds 6b and 6d showed an interesting cytotoxic
      profile and were subjected to further cytotoxic evaluation, DNA binding
      properties and molecular modelling studies. The evaluation of the cytotoxic
      activity of compounds 6b and 6d against pairs of cisplatin-sensitive and 
      resistant ovarian tumour cells shows that both compounds may be endowed with
      interesting antitumour properties because they are able to circumvent cisplatin
      resistance in A2780cisR, CH1cisR and Pam 212-ras tumour cells. On the other hand,
      DNA binding data indicate that compounds 6b and 6d are able to intercalate
      stronger than acridine within the double helix. Both compounds displace ethidium
      bromide with an efficiency ten times higher than acridine from several linear
      double-stranded DNAs and induce 43 degrees unwinding in supercoiled pBR322 DNA
      while acridine unwinds pBR322 DNA by only 24 degrees. Altogether these data
      indicate that the significant conformational changes induced by compounds 6b and
      6d in the double helix are due to a bis-intercalative DNA binding mode. We
      propose that binding to DNA through bisintercalation might be at least in part
      responsible for the remarkable cytotoxic properties of these acridine
      derivatives. The complex of 6b with d(GCGCGC)(2) in the four possible
      orientations that the ligand can adopt when binding to the DNA hexamer have been
      modelled and subjected to molecular dynamics simulations with the aim of
      evaluating the binding preferences of this bisintercalating agent into the DNA
      molecule. The predictions suggest that 6b binds to d(GCGCGC)(2) with a parallel
      orientation of the chromophores relative to each other and with a preference for
      binding through the minor groove of the hexamer. The possible relevance of these
      findings to the process of bisintercalation and the antitumour profile of these
      compounds is discussed in this paper.

PMID- 11960666
TI  - Synthesis and DNA interaction of a mixed proflavine-phenanthroline Troger base.
AB  - We report the synthesis of an asymmetric Troger base containing the two well
      characterised DNA binding chromophores, proflavine and phenanthroline. The mode
      of interaction of the hybrid molecule was investigated by circular and linear
      dichroism experiments and a biochemical assay using DNA topoisomerase I. The data
      are compatible with a model in which the proflavine moiety intercalates between
      DNA base pairs and the phenanthroline ring occupies the DNA groove. DNase I
      cleavage experiments were carried out to investigate the sequence preference of
      the hybrid ligand and a well resolved footprint was detected at a site
      encompassing two adjacent 5'-GTC.5-GAC triplets. The sequence preference of the
      asymmetric molecule is compared to that of the symmetric analogues.

PMID- 11960667
TI  - Synthesis and antibacterial activity of dual-action agents of a beta-lactam
      antibiotic with cytotoxic agent mitozolomide or temozolomide.
AB  - Dual-action agents 5a-f and 12a-f, a beta-lactam antibiotic combined with a
      cytotoxic agent, mitozolomide (Meto) or temozolomide (Temo), were synthesised.
      The antibacterial activity (MICs) of the dual-action agents has been determined
      against a panel of bacteria including several beta-lactamase producing strains.
      The tests showed 5a-f active against the non-beta-lactamase producing methicillin
      sensitive Staphylococcus aureus (MSSA) strains, however, little synergistic
      effect between the beta-lactam and the cytotoxic agent was observed. 12a-f
      demonstrated some synergistic effect against bacteria. 12a, in particular, is
      active against ampicillin resistant (beta-lactamase-producing) strains of
      Serratia marcescens.

PMID- 11960668
TI  - Synthesis and cytotoxic evaluation of alpha-methylene-gamma-butyrolactone bearing
      naphthalene and naphtho[2,1-b]furan derivatives.
AB  - Naphthalene alpha-methylene-gamma-butyrolactones exhibits a unique cytotoxicity
      profile. They are highly cytostatic for leukaemia cancer cells but are not
      cytocidal. For almost all the solid tumours tested, they are both cytostatic and
      cytocidal. Substitution of a bromo atom on either naphthalene or both naphthalene
      and gamma-phenyl moiety of the lactone enhanced potency while retaining the same
      cytotoxicity profile. The tricyclic naphtho[2,1-b]furan derivatives, prepared
      from 2-hydroxy-1-naphthaldehyde in an efficient pathway, also possess the same
      cytotoxicity profile.

PMID- 11960669
TI  - 3-O-substituted benzyl pyridazinone derivatives as COX inhibitors.
AB  - New 3-O-substituted benzyl pyridazinone compounds have been synthesised and
      evaluated for their cyclooxygenase inhibitory activity and COX-2 selectivity.
      Among the compounds synthesised, three compounds (11b-11d) have shown in vitro
      COX-2 selectivity. These compounds have been evaluated for their in vivo
      potential using carrageenan-induced rat paw edema assay. One compound (11b)
      showed 32% anti-inflammatory activity at 30 mgkg(-1) dose.

PMID- 11960670
TI  - Synthesis and immunofluorescence assay of a new biotinylated paclitaxel.
AB  - 7-(5'-Biotinylamidopropanoyl)paclitaxel was synthesised by chemical methods; its
      immunofluorescence assay and the cell uptake experiments were performed by use of
      human leukemia U937 cells. The results indicate that paclitaxel is arresting cell
      cycle at the G(2)M phase only.

PMID- 11960672
TI  - Protein adducts of malondialdehyde and 4-hydroxynonenal in livers of iron loaded
      rats: quantitation and localization.
AB  - Pathophysiological mechanisms for hepatocellular injury, fibrosis and/or
      cirrhosis in hepatic iron overload are poorly understood. An increase in
      intracellular transit pool of iron can catalyze peroxidation of lipids to produce
      reactive aldehydes such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE).
      Covalent binding of such lipid aldehydes with proteins may cause impairment in
      cellular function and integrity. This investigation was focused on quantitative
      determination of MDA and HNE-protein adducts, and to establish a correlation
      between iron deposition and formation and localization of MDA and HNE-protein
      adducts, using immunohistochemistry. To achieve iron overload, male SD rats were
      fed a 2.5% carbonyl iron-supplemented diet for six weeks, while control animals
      received standard diet. Total iron as well as low molecular weight chelatable
      iron (LMWC-Fe) in the hepatic tissue of rats fed the iron supplemented diet
      increased significantly ( approximately 14- and approximately 15-fold,
      respectively). Quantitative ELISA for MDA-and HNE-protein adducts showed
      remarkable increases of 186 and 149%, respectively, in the liver homogenates of
      rats fed the iron-supplemented diet. Sections of liver stained for iron showed
      striking iron deposits in periportal (zone 1) hepatocytes, which was less
      dramatic in midzonal (zone 2) cells. Livers from iron-loaded rats showed strong,
      diffuse staining for both MDA and HNE adducts, which was highly pronounced in
      centrilobular (zone 3) hepatocytes, but was also evident in midzonal cells (zone
      2). The demonstration of greater formation of both MDA and HNE-protein adducts
      provides evidence of iron-catalyzed lipid peroxidation in vivo. Although in this
      model of iron overload there was no evidence of tissue injury, our results
      provide an account of some of the initiating factors or early molecular events in
      hepatocellular damage that may lead to the pathological manifestations seen in
      chronic iron overload.

PMID- 11960673
TI  - Effects of furazolidone, PCB77, PCB126, Aroclor 1248, paraquat and p,p'-DDE on
      transketolase activity in embryonal chicken brain.
AB  - The effect of in ovo exposure to PCBs, DDE and paraquat on transketolase activity
      was measured in 19-day-old chicken embryos. Furazolidone was used as a positive
      control for decreased activity of the enzyme. The potency of contaminants to
      interact with transketolase was also tested in an in vitro system, using control
      brain 7000xg supernatants containing the enzyme. No effects were found on
      transketolase activity after in ovo or in vitro exposure to PCB126, Aroclor, DDE
      or paraquat. PCB77 decreased transketolase activity in vitro, but only at
      concentrations that, extrapolated to in ovo exposure, would be lethal to the
      embryo. Furazolidone decreased transketolase activity both in ovo and in vitro.
      For this contaminant, thiamine residues were analysed in the yolk sacs, but no
      differences were found between exposed and non-exposed eggs. Transketolase is
      dependent on thiamine pyrophosphate as a cofactor, and therefore, the decreased
      enzyme activity could be the result of an interaction between furazolidone and
      thiamine metabolism. Since thiamine residues were not affected by furazolidone
      and transketolase inhibition in vitro was similar to the inhibition after in ovo
      exposure, it was concluded that furazolidone interacted with transketolase on the
      enzymatic level rather than by a depletion of thiamine.

PMID- 11960674
TI  - In vitro cytokine release from rat type II pneumocytes and alveolar macrophages
      following exposure to JP-8 jet fuel in co-culture.
AB  - Alveolar type II epithelial cells (AIIE) and pulmonary alveolar macrophages (PAM)
      are involved in pulmonary toxicity of JP-8 jet fuel exposure. To further
      elucidate their inflammatory mechanisms, the effect(s) of JP-8 jet fuel on
      cytokine secretion were examined in a transformed rat AIIE cell line (RLE-6TN)
      culture alone, primary PAM (from Fischer 344 rats) culture alone, and the co
      culture of AIIE and primary PAM. A series of JP-8 jet fuel concentrations (0-0.8
      microg/ml), which may actually be encountered in alveolar space of lungs exposed
      in vivo, were placed in cell culture for 24 h. Cultured AIIE alone secreted
      spontaneously interleukin (IL)-1beta and -6 [below detectable limits for IL-10
      and tumor necrosis factor-alpha (TNF-alpha)], whereas cultured PAM alone secreted
      IL-1beta, -10, and TNF-alpha, in a concentration-dependent manner. These data
      suggest that the release of cytokines, not only from PAM but also from AIIE
      cells, may contribute to JP-8 jet fuel-induced inflammatory response in the
      alveolar space. However, the co-cultures of AIIE and PAM showed no significant
      changes in IL-1beta, -6, and TNF-alpha at any JP-8 jet fuel concentration
      compared to control values. These cytokine levels in co-cultures of AIIE and PAM
      were inversely related to these of cultured AIIE or PAM alone. Interestingly, IL
      10 levels in the co-culture system were concentration-dependently increased up to
      1058% at JP-8 concentrations of 0.8 microg/ml, although under detectable limits
      in cultured AIIE alone and no significant concentration change in cultured PAM
      alone. It appears that PAM may possibly act via paracrine and/or autocrine
      pathways to signal AIIE cells to regulate cytokine release.

PMID- 11960676
TI  - Dichloroacetate toxicokinetics and disruption of tyrosine catabolism in B6C3F1
      mice: dose-response relationships and age as a modifying factor.
AB  - Dichloroacetate (DCA) is a rodent carcinogen commonly found in municipal drinking
      water supplies. Toxicokinetic studies have established that elimination of DCA is
      controlled by liver metabolism, which occurs by the cytosolic enzyme glutathione
      S-transferase-zeta (GST-zeta). DCA is also a mechanism based inhibitor of GST
      zeta, and a loss in GST-zeta enzyme activity occurs following repeated doses or
      prolonged drinking water exposures. GST-zeta is identical to an enzyme that is
      part of the tyrosine catabolism pathway known as maleylacetoacetate isomerase
      (MAAI). In this pathway, GST-zeta plays a critical role in catalyzing the
      isomerization of maleylacetoacetate to fumarylacetoacetate. Disruption of
      tyrosine catabolism has been linked to increased cancer risk in humans. We
      studied the elimination of i.v. doses of DCA to young (10 week) and aged (60
      week) mice previously treated with DCA in their drinking water for 2 and 56
      weeks, respectively. The diurnal change in blood concentrations of DCA was also
      monitored in mice exposed to three different drinking water concentrations of DCA
      (2.0, 0.5 and 0.05 g/l). Additional experiments measured the in vitro metabolism
      of DCA in liver homogenates prepared from treated mice given various recovery
      times following treatment. The MAAI activity was also measured in liver cytosol
      obtained from treated mice. Results indicated young mice were the most sensitive
      to changes in DCA elimination after drinking water treatment. The in vitro
      metabolism of DCA was decreased at all treatment rates. Partial restoration (
      approximately 65% of controls) of DCA elimination capacity and hepatic GST-zeta
      activity occurred after 48 h recovery from 14 d 2.0 g/l DCA drinking water
      treatments. Recovery from treatments could be blocked by interruption of protein
      synthesis with actinomycin D. MAAI activity was reduced over 80% in liver cytosol
      from 10-week-old mice. However, MAAI was unaffected in 60-week-old mice. These
      results indicate that in young mice, inactivation and re-synthesis of GST-zeta is
      a highly dynamic process and that exogenous factors that deplete or reduce GST
      zeta levels will decrease DCA elimination and may increase the carcinogenic
      potency of DCA. As mice age, the elimination capacity for DCA is less affected by
      reduced liver metabolism and mice appear to develop some toxicokinetic
      adaptation(s) to allow elimination of DCA at rates comparable to naive animals.
      Reduced MAAI activity alone is unlikely to be the carcinogenic mode of action for
      DCA and may in fact, only be important during the early stages of DCA exposure.

PMID- 11960675
TI  - A venom extract from the sea anemone Bartholomea annulata produces haemolysis and
      lipid peroxidation in mouse erythrocytes.
AB  - The haemolytic and peroxidative effects of crude extracts from Bartholomea
      annulata, a common Caribbean sea anemone, were investigated in erythrocytes
      isolated from NIH male albino mice. Significant concentration-dependent effects
      were found on both haemolysis (evaluated as release of haemoglobin) and lipid
      peroxidation (as a common index of oxidative damage to membrane lipids) in red
      blood cells. Moreover, the incubation of erythrocytes in the presence of either a
      general antioxidant, reduced glutathione (GSH, 50 microM), or an iron chelator,
      desferrioxamine (DFA, 10 microM), resulted in a significant attenuation of
      haemolysis in both cases. In light of these findings, the in vitro toxicological
      characterization of the venom, as well as the involvement of oxygen radical
      mediated membrane damage as a potential mechanism of toxicity associated with
      haemolysis are discussed.

PMID- 11960677
TI  - Developmental lead exposure differentially alters the susceptibility to
      chemoconvulsants in rats.
AB  - Sprague-Dawley rats were exposed to lead (Pb) acetate (0.2% w/v) in drinking
      water from postnatal day (PN) 1 through PN 25 followed by discontinuing Pb
      exposure for 25 days. The convulsion signs produced by the i.v. infusion of
      convulsants were observed at PN 25 and PN 50. Pb exposure significantly decreased
      pentylenetetrazol (PTZ)-, picrotoxin (PIC)-, and strychnine (STRY)-induced, but
      increased N-methyl-D-aspartate (NMDA) and 4-aminopyridine (4-AP)-induced
      convulsion thresholds at PN 25. After rehabilitation, the Pb-induced changes in
      PTZ-, NMDA- and 4-AP- induced convulsions persisted till PN 50. In contrast, the
      thresholds for PIC- and STRY-induced convulsions were reversed to an increase at
      PN 50. Blood Pb concentrations were 46.9 +/- 6.8 and 11.4 +/- 1.1 microg/dl at PN
      25 and PN 50, respectively. The results demonstrate that developmental Pb
      exposure does not result in a global and persistent lowering of threshold in
      response to convulsive stimuli and the Pb-induced changes may be due to a
      selective modulation of inhibitory and excitatory neurotransmission depending on
      age and Pb concentration in blood.

PMID- 11960678
TI  - Interactions between pesticides and components of pesticide formulations in an in
      vitro neurotoxicity test.
AB  - Organophosphate (OP) pesticides are often used in combination with one another
      and with the components of formulations. Evidence already exists for interactions
      in the neurotoxic effects of OPs through interference with metabolism, but there
      is also potential for interactions related directly to cell damage. The purpose
      of this work was to investigate this possibility for OPs and the components of
      one of their common formulations in vitro. NB2a neuroblastoma cells were induced
      to differentiate in the presence of the OPs diazinon and chlorpyrifos, in
      combination with a commercial formulation (identified as Commercial Formulation
      1) of the compounds and, independently, the components of that formulation. The
      compounds were tested in pairs in various proportions and the resulting
      inhibition of neurite outgrowth was measured by light microscopy and quantitative
      image analysis. Interactions were determined in terms of enhanced or reduced
      effects of the paired compounds in comparison with the expected additive effects
      estimated from the effects of each compound on its own. Synergism was detected
      between combinations of: 10 microM chlorpyrifos and 500 nM pyrethrum;
      chlorpyrifos and one of the solvents (regular spirit) found in Commercial
      Formulation 1. All other combinations of OPs and products were additive in their
      neurotoxicity. The data suggest that exposure to multiple OP-containing pesticide
      formulations may lead to synergistic neurotoxicity by a direct mechanism at the
      cellular level.

PMID- 11960679
TI  - Brainstem control of head movements during orienting; organization of the
      premotor circuits.
AB  - When an object appears in the visual field, animals orient their head, eyes, and
      body toward it in a well-coordinated manner (orienting movement). The head
      movement is a major portion of the orienting movement. Interest in the neural
      control of head movements in the monkey and human have increased in the 1990's,
      however, fundamental knowledge about the neural circuits controlling the
      orienting head movement continues to be based on a large number of experimental
      studies performed in the cat. Thus, it is crucial now to summarize information
      that has been clarified in the cat for further advancement in understanding the
      neural control of head movements in different animal species. The superior
      colliculus (SC) has been identified as the primary brainstem center controlling
      the orienting. Its output signal is transmitted to neck motoneurons via two major
      separate pathways: one through the reticulospinal neurons (RSNs) in the pons and
      medulla and the other through neurons in Forel's field H (FFH) in the
      mesodiencephalic junction. The tecto-reticulo-spinal pathway controls orienting
      chiefly in the horizontal direction, while the tecto-FFH-spinal pathway controls
      orienting in the vertical direction. In each pathway, a subgroup of neurons
      functions as premotor neurons for both extraocular and neck motoneurons, while
      others are specified for each, which allows both coordinated and separate control
      of eye and head movements. Head movements almost always produce shifts in the
      center of gravity that might cause postural disturbances. The postural
      equilibrium may be maintained by transmitting the orienting command to the limb
      segments via descending axons of the reticulospinal and long propriospinal
      neurons. The SC and brainstem relay neurons receive descending inputs from higher
      order structures such as the cerebral cortex, cerebellum, and basal ganglia.
      These inputs may serve context-dependent control of orienting by modulating the
      activities of the primary brainstem pathways.

PMID- 11960680
TI  - The TRP family of cation channels: probing and advancing the concepts on receptor
      activated calcium entry.
AB  - Stimulation of membrane receptors linked to a phospholipase C and the subsequent
      production of the second messengers diacylglycerol and inositol-1,4,5
      trisphosphate (InsP(3)) is a signaling pathway of fundamental importance in
      eukaryotic cells. Signaling downstream of these initial steps involves
      mobilization of Ca(2+) from intracellular stores and Ca(2+) influx through the
      plasma membrane. For this influx, several contrasting mechanisms may be
      responsible but particular relevance is attributed to the induction of Ca(2+)
      influx as consequence of depletion of intracellular calcium stores. This
      phenomenon (frequently named store-operated calcium entry, SOCE), in turn, may be
      brought about by various signals, including soluble cytosolic factors,
      interaction of proteins of the endoplasmic reticulum with ion channels in the
      plasma membrane, and a secretion-like coupling involving translocation of
      channels to the plasma membrane. Experimental approaches to analyze these
      mechanisms have been considerably advanced by the discovery of mammalian homologs
      of the Drosophila cation channel transient receptor potential (TRP). Some members
      of the TRP family can be expressed to Ca(2+)-permeable channels that enable SOCE;
      other members form channels activated independently of stores. TRP proteins may
      be an essential part of endogenous Ca(2+) entry channels but so far expression of
      most TRP cDNAs has not resulted in restitution of channels found in any mammalian
      cells, suggesting the requirement for further unknown subunits. A major exception
      is CaT1, a TRP channel demonstrated to provide Ca(2+)-selective, store-operated
      currents identical to those characterized in several cell types. Ongoing and
      future research on TRP channels will be crucial to understand the molecular basis
      of receptor-mediated Ca(2+) entry, with respect to the structure of the entry
      channels as well as to the mechanisms of its activation and regulation.

PMID- 11960681
TI  - From single extracellular unit recording in experimental and human Parkinsonism
      to the development of a functional concept of the role played by the basal
      ganglia in motor control.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects
      the whole basal ganglia (BG). Various techniques have been used to study BG
      physiology and pathophysiology. Among these, extracellular single unit recording
      remains of particular importance. An impressive number of studies of BG
      electrophysiological activity have been carried out, both in non-human and in
      human primates, but the data collected show many omissions and disparities. BG
      activity has been well defined in the physiological situation, but remains far
      from clear in the Parkinsonian and virtually unexplored in the dopamine (DA)
      replacement situation. This paper provides a brief synopsis of (i) recording
      techniques and (ii) BG electrophysiological activity in normal, Parkinsonian, and
      dopamine-replacement situations. We have restricted the data used to those
      obtained in BG structures of human and non-human primates. Only single unit
      recordings have been reported and four electrophysiological characteristics
      retained: mean firing frequency, firing pattern, periodic oscillation, and
      response to both passive and active movement. We have attempted to summarize (i)
      the commonly accepted characteristics of each BG structure in the three
      situations, (ii) discrepancies that exist, and (iii) missing elements. Then, the
      main successive theories aimed to explain the role played by BG in motor control
      are presented and discussed in the light of the most recently obtained results
      using the latest technological advances.

PMID- 11960682
TI  - Cell and nucleus deformation in compressed chondrocyte-alginate constructs:
      temporal changes and calculation of cell modulus.
AB  - Mechanical loading is essential for the homeostasis of articular cartilage and
      may be necessary for achieving functional tissue engineered cartilage repair
      using isolated cells seeded in scaffolds such as alginate. Chondrocyte
      mechanotransduction is poorly understood, but may involve cell deformation and
      associated distortion of intracellular organelles. The present study used
      confocal microscopy to examine cell and nucleus morphology in isolated
      chondrocytes compressed in alginate constructs. Compression of 2% alginate
      resulted in cell deformation from a spherical to an oblate ellipsoid morphology
      with conservation of cell volume. Cell deformation was associated with
      deformation, to a lesser degree, of the nucleus. Despite constant cell
      deformation over a 25 min period of static compression, the nucleus deformation
      reduced significantly, particularly in the axis perpendicular to the applied
      compression. Constructs made of a lower alginate concentration exhibited a
      reduced compressive modulus with an altered cellular response to compression. In
      1.2% alginate, compression resulted in cell deformation which was initially of a
      similar magnitude to that in 2% alginate but subsequently reduced over a 60 min
      period reflecting the viscoelastic behaviour of the gel. This phenomenon enabled
      the calculation of a stress-strain relationship for the cell with an estimated
      Young's modulus value of approx. 3 kPa.

PMID- 11960683
TI  - Cytochrome c forms complexes and is partly reduced at interaction with GPI
      anchored alkaline phosphatase.
AB  - Cytochrome (cyt) c forms complexes, undergoes a conformational change and becomes
      partly reduced at interaction with membrane anchored alkaline phosphatase (AP), a
      glycoprotein which is released into the body fluid in forms differing in
      hydrophobicity. The proportion of products formed in the mixtures depends on pH,
      ionic strength, temperature and the buffer composition. The reaction terminates
      in an equilibrium between cyt c(FeII) and other cyt c conformers. Optimal
      conditions for the rate of the reaction are 100 mM glycine/NaOH, pH 9.7-9.9, at
      which 68-74% of cyt c is found in the reduced state. The interaction affects
      compactness of the haem cleft as shown by changes induced in CD spectra of the
      Soret region and changes in optical characteristics of phenylalanine, tyrosine
      and tryptophan residues. Differential scanning calorimetry of AP+cyt c mixtures
      revealed a creation of at least two types of complexes. A complex formed by non
      coulombic binding prevails at substoichiometric AP/cyt c ratios, at higher ratios
      more electrostatic attraction is involved and at 1:1 molar ratio an apparent
      complexity of binding forces occurs. The rapid phase of the cyt c(FeII) formation
      depends on the presence of the hydrophobic alkylacylphosphoinositol
      (glycosylphosphatidylinositol) moiety, the protein part of the enzyme
      participates in an electrostatic and much slower phase of cyt c(FeII) creation.
      The results show that non-coulombic interaction may participate at interaction of
      cyt c with cellular proteins.

PMID- 11960684
TI  - Iodination significantly influences the binding of human transferrin to the
      transferrin receptor.
AB  - The human transferrin receptor (TfR) and its ligand, the serum iron carrier
      transferrin, serve as a model system for endocytic receptors. Although the
      complete structure of the receptor's ectodomain and a partial structure of the
      ligand have been published, conflicting results still exist about the magnitude
      of equilibrium binding constants, possibly due to different labeling techniques.
      In the present study, we determined the equilibrium binding constant of purified
      human TfR and transferrin. The results were compared to those obtained with
      either iodinated TfR or transferrin. Using an enzyme-linked assay for receptor
      ligand interactions based on the published direct calibration ELISA technique, we
      determined an equilibrium constant of Kd=0.22 nM for the binding of unmodified
      human Tf to surface-immobilized human TfR. In a reciprocal experiment using
      soluble receptor and surface-bound transferrin, a similar constant of Kd=0.23 nM
      was measured. In contrast, covalent labeling of either TfR or transferrin with
      125I reduced the affinity 3-5-fold to Kd=0.66 nM and Kd=1.01 nM, respectively.
      The decrease in affinity upon iodination of transferrin is contrasted by an only
      1.9-fold decrease in the association rate constant, suggesting that the
      iodination affects rather the dissociation than the association kinetics. These
      results indicate that precautions should be taken when interpreting equilibrium
      and rate constants determined with covalently labeled components.

PMID- 11960685
TI  - Differential lipoprotein transport pathways of K-vitamins in healthy subjects.
AB  - Vitamin K is a group name for K1 (phylloquinone) and K2 (menaquinones). Both
      forms contribute to the tissue vitamin K status. Following intestinal absorption,
      the serum transport of these lipophilic compounds to their target tissues takes
      place via lipoproteins. In previous studies we have found that K1 is
      preferentially accumulated in the liver, whereas menaquinones have a more
      widespread distribution pattern. Here we have tested whether these differences
      may be explained by the different liposolubility of the various K-vitamers,
      resulting in their association with different lipoprotein particles. Six healthy
      male volunteers received a mixture containing 2 micromol of each of three K
      vitamers (K1, MK-4, and MK-9) dissolved in corn oil. Blood was obtained at
      baseline and at different time intervals after intake for the measurement of
      vitamin K in serum and in the lipoprotein fractions. During the first 4 h after
      intake all K-vitamins were found to be associated predominantly with the
      triacylglycerol-rich lipoprotein (TGRLP) fraction. Since the TGRLP fraction is
      mainly cleared by the liver, this suggests that initially most of the K-vitamins
      are transported to the liver. In contrast to K1, however, both menaquinones
      investigated were also found in TGRLP and low-density lipoprotein, whereas MK-4
      was even present in high-density lipoprotein. This explains why menaquinones may
      have a different distribution profile and suggests a relatively large impact of
      menaquinones on extra-hepatic vitamin K status than generally assumed. Moreover,
      the very long half-life time of MK-9 in the circulation indicates that it may
      form a more constant source of vitamin K than are either K1 or MK-4.

PMID- 11960686
TI  - Effects of interleukin-15 (IL-15) on adipose tissue mass in rodent obesity
      models: evidence for direct IL-15 action on adipose tissue.
AB  - Interleukin-15 (IL-15) is a proinflammatory cytokine with multifunctional effects
      outside the immune system. Previous studies have indicated that treatment of
      normal rats with IL-15 reduces white adipose tissue (WAT) mass, but it was
      unclear if these effects were direct or indirect. In the present study, the
      effects of IL-15 on WAT mass and lipid metabolism were studied in two genetic
      models of obesity: the leptin receptor-negative fa/fa Zucker rat and the leptin
      deficient ob/ob mouse. Lean Zucker rats, lean (+/+), and obese mice (ob/ob)
      responded to IL-15 with reductions in WAT mass and lipoprotein lipase activity
      (LPL), with no decreases in food intake. In contrast, fa/fa Zucker rats did not
      respond to IL-15 administration by any of the above measures of fat mass or lipid
      metabolism. In addition, ribonuclease protection assays (RPAs) were used to
      demonstrate that all three subunits (gamma(c), beta and alpha) of the IL-15
      receptor complex are expressed by rat and mouse WAT, suggesting that the effects
      of IL-15 on adipose tissue metabolism could be direct. Additionally, the fa/fa
      rats expressed 84% lower levels of the gamma(c) signaling receptor subunit than
      lean Zucker rats, suggesting this decrease may play a role in the lack of adipose
      tissue response to IL-15 in the fa/fa genotype and lending further support for a
      direct action of IL-15 on adipose tissue.

PMID- 11960687
TI  - Subcellular localization of endo-beta-N-acetylglucosaminidase and high-mannose
      type free N-glycans in plant cell.
AB  - Subcellular distribution of plant endo-beta-N-acetylglucosaminidase (endo-beta
      GlcNAc-ase) and high-mannose type free N-glycans produced by the endoglycosidase
      has been analyzed using cotyledons of pumpkin seedlings as the model plant cells.
      Each organelle in the cotyledons was fractionated by ultracentrifugation with the
      sucrose density gradient system and the endo-beta-GlcNAc-ase activity in each
      fraction was assayed with fluorescence labeled N-glycans as substrates. The
      endoglycosidase activity was exclusively recovered in the soluble fraction
      (cytosol fraction) but not in other specific organellar fractions, suggesting
      that the endoglycosidase would reside predominantly in the cytosol. The
      quantitative analysis of high-mannose type free N-glycans occurring in each
      fraction showed that more than 70% of the free N-glycans was recovered from the
      soluble fraction, suggesting the endoglycosidase would work in the cytosol and
      the resulting free N-glycans would accumulate in the same fraction. The pumpkin
      endo-beta-GlcNAc-ase (endo-CM) partially purified from the cotyledons showed
      optimum activity around pH 6.5, supporting this enzyme would reside in the
      cytosol. Furthermore, the detailed analysis of substrate specificity of endo-CM
      using various high-mannose type N-glycans showed that the pumpkin enzyme, as well
      as other plant endo-beta-N-acetylglucosaminidases, were highly active toward the
      high-mannose type glycans bearing the Man(alpha1)-2Man(alpha1)-3Man(beta1)
      structural unit.

PMID- 11960688
TI  - Determination of intracellular glutathione and thiols by high performance liquid
      chromatography with a gold electrode at the femtomole level: comparison with a
      spectroscopic assay.
AB  - Glutathione (GSH) is an important thiol, which has multiple functions in human
      metabolism, including the detoxification of xenobiotics, radioprotection and
      antioxidant defense. Here we provide a sensitive and specific method to quantify
      intracellular GSH and other thiols using an electrochemical detector coupled to a
      high performance liquid chromatograph (HPLC-ECD). This HPLC-ECD system includes a
      specially devised gold electrode with a large surface area and a thin gasket to
      provide an extremely high sensitivity to thiols. The standard curve for GSH
      showed a good linear relationship at low femtomole levels (r=0.970). We could
      simultaneously detect GSH, cysteine, N-acetylcysteine, gamma-glutamyl-cysteine
      and cysteinyl-glycine by this method. We compared the specificity and sensitivity
      of this method with those of the conventional spectroscopic method by measuring
      the amounts of GSH in HL-60 cell extracts. Although the values obtained from
      these methods were closely correlated (r=0.984), the electrochemical method was
      much more specific for GSH. This method could detect 2 fmol of GSH and was 6
      orders and 2-3 orders of magnitude more sensitive than the spectroscopic method
      and previous methods using HPLC, respectively. As an example of the application
      of this method, we demonstrated that the time-dependent alteration in
      intracellular GSH and cysteine levels could be easily measured using buthionine
      sulfoximine, an inhibitor of GSH synthesis. On the basis of these results, the
      advantage of this electrochemical method is extremely sensitive and specific to
      detect femtomole levels of GSH and other various thiols.

PMID- 11960689
TI  - Glycogen phosphorylase is activated in response to glucose deprivation but is not
      responsible for enhanced glucose transport activity in 3T3-L1 adipocytes.
AB  - We have previously shown that glucose deprivation activates glucose transport in
      a time- and protein synthesis-dependent fashion in 3T3-L1 adipocytes, a mouse
      cell line. Coincident with this is loss of glycogen. Because glycogen
      phosphorylase (GP) is responsible for glycogen degradation, we have examined its
      regulation to determine the relationship between transport activation and
      glycogen turnover. We first cloned the adipose GP cDNA and found sequence
      similarity to rat and human liver GP. Because the mouse liver GP cDNA sequence
      was unavailable, we cloned this cDNA as well and showed 100% identity between
      mouse adipose and liver sequences. A 3.1 kb transcript was readily observed in
      total RNA isolated from mouse liver or adipose by Northern blot analysis but,
      surprisingly, not in either total or poly(A) selected RNA from 3T3-L1 adipocytes.
      To evaluate regulation in 3T3-L1 adipocytes, we amplified GP mRNA from total RNA
      using multiplex, semi-quantitative PCR but found that expression did not change
      in response to deprivation. GP protein levels did not change either. However,
      endogenous GP activity from glucose-deprived cells was significantly elevated
      relative to controls, due to an increase in the phosphorylated form of GP (GPa).
      Finally, we overexpressed GP to determine its direct influence on the glucose
      transport system. These results were negative, which suggests that the nutrient
      control of glucose transport and GP occurs independently despite kinetic
      similarities in transport activation and glycogen turnover.

PMID- 11960690
TI  - Effect of lecithin and MgCO3 as additives on the enzymatic activity of carbonic
      anhydrase encapsulated in poly(lactide-co-glycolide) (PLGA) microspheres.
AB  - A model enzyme, carbonic anhydrase, was encapsulated and released from
      poly(lactide-co-glycolide) (PLGA) microspheres (1-3 microm) made by a novel phase
      inversion technique. Lecithin was used as a surfactant in the encapsulation
      process and was incorporated in either the organic phase, aqueous phase, both
      phases, or not at all. Additional microspheres were also made with lecithin
      incorporated in the aqueous phase and a basic salt, MgCO3, in the polymeric
      phase. Released carbonic anhydrase, protein extracted from microspheres, or
      enzyme incubated with lecithin and PLGA were analyzed via HPLC and activity assay
      to determine the effect of these additives on protein integrity and activity.
      Lecithin in the aqueous phase appeared to increase the fraction of enzyme in
      monomeric form as well as its activity for both extracted protein and released
      protein as compared to the other formulations without MgCO3. Incubation of enzyme
      with PLGA degradation products indicated that the acidic environment within the
      microspheres aids in the irreversible inactivation of the encapsulated protein.
      Addition of MgCO3 further increased the amount of monomer in both the extracted
      and released protein by decreasing the amount of acid-induced cleavage and
      noncovalent aggregation, but still greatly decreased the activity of the enzyme.

PMID- 11960691
TI  - Cloning and nucleotide sequence analysis of the Streptococcus sobrinus gtfU gene
      that produces a highly branched water-soluble glucan.
AB  - Streptococcus sobrinus has four gtf genes, gtfI, gtfS, gtfT, and gtfU, on the
      chromosome. These genes correspond respectively to the enzymes GTF-I, GTF-S1, GTF
      S2, and GTF-S3. An Escherichia coli MD66 clone that contained the S. sobrinus
      gtfU gene was characterized. Immunological properties showed that the protein
      produced by the E. coli MD66 clone was similar to S. sobrinus GTF-S1. Biological
      properties and a linkage analysis of the glucans by 13C NMR spectrometry revealed
      that the protein produced by the E. coli MD66 clone was GTF-S1.

PMID- 11960692
TI  - The molecular pathology of Kaposi's sarcoma-associated herpesvirus.
AB  - Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is the eighth and most
      recently identified human herpesvirus (HHV-8). KSHV was discovered in 1994 by
      Chang et al. who used representational difference analysis to search for DNA
      sequences present in AIDS-associated KS but not in adjacent normal skin [1]. The
      virus has since been shown to be specifically associated with all forms of this
      disease and has fulfilled all of Hill's criteria for causation (reviewed in ).
      KSHV is also found in all cases of primary effusion lymphoma and in a
      plasmablastic variant of multicentric Castleman's disease. Over the last few
      years a wealth of data has been gained on the role of KSHV genes during
      infection. This review is an attempt to assemble this information into a more
      complete picture of how KSHV may cause disease.

PMID- 11960693
TI  - GTPase activating proteins: critical regulators of intracellular signaling.

PMID- 11960694
TI  - Activation of the p53 tumor suppressor protein.
AB  - The p53 tumor suppressor gene plays an important role in preventing cancer
      development, by arresting or killing potential tumor cells. Mutations within the
      p53 gene, leading to the loss of p53 activity, are found in about half of all
      human cancers, while many of the tumors that retain wild type p53 carry mutations
      in the pathways that allow full activation of p53. In either case, the result is
      a defect in the ability to induce a p53 response in cells undergoing oncogenic
      stress. Significant advances have been made recently in our understanding of the
      molecular pathways through which p53 activity is regulated, bringing with them
      fresh possibilities for the design of cancer therapies based on reactivation of
      the p53 response.

PMID- 11960695
TI  - Contributions of Myc to tumorigenesis.
AB  - Despite intensive research, the mechanisms by which deregulation of myc gene
      expression contributes to tumorigenesis are still not fully resolved and many
      aspects are still enigmatic. Several recent reviews, including one published in
      this series a few months ago, have summarized recent progress in our
      understanding of the biochemistry of Myc proteins [Eisenmann, Genes Dev. (2001)
      in press; Amati et al., Biochim. Biophys. Acta 1471 (2001) 135-145]. Also, the
      evidence documenting a central role of Myc proteins in human tumorigenesis has
      been extensively reviewed [Henriksson and Luscher, Cancer Res. 68 (1996) 109
      182]. In this article, we will argue that current progress allows us to present
      testable hypotheses on how Myc affects specific properties of transformed cells.

PMID- 11960696
TI  - Cyclin D-dependent kinases, INK4 inhibitors and cancer.
AB  - The Cyclin D-Cdk4,6/INK4/Rb/E2F pathway plays a key role in controlling cell
      growth by integrating multiple mitogenic and antimitogenic stimuli. The
      components of this pathway are gene families with a high level of structural and
      functional redundancy and are expressed in an overlapping fashion in most tissues
      and cell types. Using classical transgenic technology as well as gene-targeting
      in ES cells, a series of mouse models have been developed to study the in vivo
      function of individual components of this pathway in both normal homeostasis and
      tumor development. These models have proven to be useful to define specific as
      well as redundant roles among members of these cell cycle regulatory gene
      families. This pathway is deregulated in the vast majority of human tumors by
      genetic and epigenetic alterations that target at least some of its key members
      such as Cyclin D1, Cdk4, INK4a and INK4b, pRb etc. As a consequence, some of
      these molecules are currently being considered as targets for cancer therapy, and
      several novel molecules, such as Cdk inhibitors, are under development as
      potential anti-cancer drugs.

PMID- 11960697
TI  - The promise of gene expression analysis in hematopoetic malignancies.

PMID- 11960699
TI  - TGF-beta is required for programmed cell death in interdigital webs of the
      developing mouse limb.
AB  - During limb formation massive cell death in the mesenchyme of the interdigital
      spaces accompanies the formation of free digits. Members of the transforming
      growth factor beta (TGF-) superfamily were discussed to play a key role in cell
      cell interactions, important in the regulation of programmed cell death (PCD).
      TGF-beta itself is believed to be involved in epithelial-mesenchymal
      interactions. Here, we demonstrate that PCD is significantly reduced in
      interdigital spaces of the developing limbs of Tgfbeta2-/-Tgfbeta3-/- double
      knockouts. The regression of interdigital webs seems to be doses-dependent as
      interdigital mesenchyme is at least partly reduced in Tgfbeta2-/-Tgfbeta3+/-
      mutants, whereas interdigital zones of Tgfbeta2-/-Tgfbeta3-/- double knockouts
      reveal only minimal signs of regression. We conclude that TGF- is a critical
      extrinsic regulator of PCD.

PMID- 11960700
TI  - Contribution of gastrin-releasing peptide and its receptor to villus development
      in the murine and human gastrointestinal tract.
AB  - Recent studies have shown that aberrantly expressed gastrin-releasing peptide
      (GRP) and its receptor (GRP-R) critically regulate tumor cell differentiation in
      colon cancers developing in humans and mice. This finding suggested that the
      ability of GRP/GRP-R to promote a well-differentiated phenotype in colon cancer
      might reflect a re-capitulation of a normal role in regulating intestinal
      organogenesis. To determine if this was the case, we compared and contrasted
      intestinal development in GRPR-/- mice with their wild type littermates. GRP/GRP
      R co-expression in wild type mice was only observed in villous enterocytes
      between N-1 and N-12. During this time frame villous growth was completely
      attenuated in GRPR-/- mice. The contribution of GRP/GRP-R to villous growth was
      due to their act in increasing enterocyte proliferation prior to N-8 but
      increasing enterocyte size thereafter. From N-12 onwards, small intestinal
      villous growth in GRPR-/- mice resumed such that no difference in this structure
      could be detected at adulthood between mice of either genotype. We next studied
      GRP/GRP-R expression in human abortuses. These proteins were co-expressed by
      villous enterocytes only between weeks 14 and 20 post-conception, a time frame
      analogous to when they are expressed in the murine intestine. Thus, this study
      shows for the first time that GRP/GRP-R play a transient and non-critical role in
      intestinal development, yet provides a rationale for their re-appearance in colon
      cancer.

PMID- 11960701
TI  - The small GTPase Rap1 is an immediate downstream target for Hoxb4 transcriptional
      regulation.
AB  - The Hox genes are a family of homeodomain-containing transcription factors which
      determine anteroposterior identity early on in development. Although a lot is now
      known about their regulation and function, very little is known of their effector
      (downstream target) genes. Here we show that the small GTPase Rap1 is a direct,
      negatively regulated target of Hoxb4 and is excluded from Hoxb4 expressing cells.

PMID- 11960702
TI  - Correlation of expression patterns of homothorax, dachshund, and Distal-less with
      the proximodistal segmentation of the cricket leg bud.
AB  - We describe the expression pattern of Gryllus homothorax (Gbhth) and dachshund
      (Gbdac), a cricket homologue of Drosophila homothorax and dachshund, together
      with localization of Distal-less or Extradenticle protein during leg development.
      We correlated their expression patterns with the morphological segmentation of
      the leg bud. The boundary of Gbhth/GbDll subdivision is correlated with the
      segment boundary of the future trochanter/femur at early stages. Gbdac expression
      subdivides the leg bud into the presumptive femur and more distal region. During
      the leg proximodistal formation, although the early expression patterns of GbDll,
      Gbdac, and Gbhth significantly differ from those of Drosophila imaginal disc,
      their expression patterns in the fully segmented Gryllus leg were similar to
      those in the Drosophila late third instar disc.

PMID- 11960703
TI  - Expression of zebrafish mab21 genes marks the differentiating eye, midbrain and
      neural tube.
AB  - Mab21 homolog in Caenorhabditis elegans is expressed in the sensory ray cells and
      determines the ray identity (Dev. Dyn. 221 (2001) 422). Similarly, vertebrate
      homologs of this gene have been shown to express in the craniofacial tissues,
      limb bud and neural tissues. We report here the cloning and expression analysis
      of two zebrafish mab21 genes. Both genes have a conserved open reading frame of
      1080 nucleotides. Phylogenetic analysis suggested that the two family subgroups
      existed prior to the divergence of vertebrates. Their expression profiles
      revealed that mab21l1 was turned on in embryos as early as 8 h post-fertilization
      (hpf) while mab21l2 was first detected at around 11 hpf. In situ hybridization
      results showed that expression of these mab21 genes marked the early
      differentiating olfactory bulbs, eye primordia, midbrain and subsequently the
      branchial pouches and neural tube.

PMID- 11960704
TI  - Expression of amylase and other pancreatic genes in Xenopus.
AB  - To better understand the relationship between the endocrine and exocrine cell
      types in the Xenopus pancreas, we have cloned the Xenopus amylase cDNA and
      compared its expression profile with that of four other pancreatic markers:
      insulin, glucagon, elastase and trypsinogen. Our results demonstrate that the
      first pancreatic marker to be expressed is insulin, exclusively in the dorsal
      pancreas. These insulin-expressing cells form small groups which resemble islets,
      but no insulin is detected in the ventral pancreas until stage 47. In contrast,
      the exocrine markers, amylase, elastase and trypsinogen are first expressed only
      in the ventral pancreas beginning at stage 41; by stage 45 their expression
      extends into the dorsal pancreas. Glucagon, on the other hand, is not expressed
      in the pancreas until stage 45. In the endocrine cell clusters we do not find
      glucagon-expressing cells surrounding insulin-expressing cells, either in the
      tadpole or in the mature frog pancreas.

PMID- 11960705
TI  - TRIM9 is specifically expressed in the embryonic and adult nervous system.
AB  - The TRIM family members are defined by the presence of the tripartite motif
      (RING, B-box and coiled-coil domains or RBCC). They have been implicated in a
      variety of processes, such as regulation of development and oncogenesis. We
      report the expression analysis of a member of this family, TRIM9. Its expression
      is mainly confined to the central nervous system. The developing neocortex, the
      dorsal thalamus, the midbrain, the basal area of the hindbrain and spinal cord
      show high level of expression during embryogenesis. In adult brain, TRIM9 is
      detected in the Purkinje cells of the cerebellum, in the hippocampus, and in the
      cortex.

PMID- 11960706
TI  - Cloning of the mouse Sef gene and comparative analysis of its expression with
      Fgf8 and Spry2 during embryogenesis.
AB  - We report the cloning and expression analysis of a mouse gene encoding a novel
      transmembrane protein. Expression of Sef is similar to that of Fgf8 and Spry2
      during early embryogenesis, being prominent in the forebrain, mid-hindbrain
      boundary, branchial arches, somites, limb bud and tailbud of mouse embryos. These
      expression profiles indicate that Fgf8, Spry2 and Sef belong to a synexpression
      group and suggest that these genes may functionally interact during embryonic
      development. From E12.5 onwards, partially distinct patterns of expression of
      these genes are observed in the neuroepithelium, sense organs and endodermal
      derived organs, that are known sites of expression of other Fgfs.

PMID- 11960707
TI  - Non-overlapping expression of Olig3 and Olig2 in the embryonic neural tube.
AB  - Olig family is a novel sub-family of basic helix-loop-helix transcription factors
      recently identified. Olig1 and Olig2 were first reported to promote
      oligodendrocyte differentiation, and later Olig2 was reported to be involved in
      motoneuron specification as well. Olig3 was isolated as a third member of Olig
      family, but its precise expression pattern is poorly understood. Here, we
      describe detailed Olig3 expression analyses in the neural tube of embryonic mice.
      Olig3 was first detected in the dorsal neural tube from the midbrain/hindbrain
      boundary to the spinal cord. In E11.5 spinal cord, Olig3 was transiently
      expressed in the lateral margin of the subventricular zone as three ventral
      clusters at the level of the p3, p2 and p0 domains, as well as in the dorsal
      neural tube. Olig3 was co-expressed with Nkx2.2 in the lateral margin of the p3
      domain. In forebrain, Olig3 was expressed in the dorsal thalamus while Olig2 was
      complementarily expressed in the ventral thalamus with an adjacent boundary at
      E12.5. Olig3 is specifically and transiently expressed in different types of
      progenitors of embryonic central nervous system and then disappears in the course
      of development.

PMID- 11960708
TI  - Expression of tissue inhibitor of metalloproteinases (TIMPs) during early cardiac
      development.
AB  - Matrix metalloproteinases (MMPs) mediate cell migration and tissue remodeling and
      are important in cardiac development. We examined the expression patterns of two
      MMP inhibitors, tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3, during
      critical stages of cardiac development. Both TIMP-2 and TIMP-3 mRNA were
      expressed in the endocardium prior to and during early cushion cell formation.
      TIMP-2 was continually expressed within the outflow tract (OT) and
      atrioventricular (AV) cushion cells at all stages examined, whereas TIMP-3 mRNA
      was undetectable in the AV cushion cells soon after their formation.
      Subsequently, TIMP-3 mRNA disappeared in cushion cells of the distal OT and this
      loss progressed toward the ventricle until eventually all of the OT cushion cells
      lacked detectable TIMP-3 transcripts. TIMP-3, but not TIMP-2, was also expressed
      within remodeling myocardium. Immunocytochemistry confirmed these findings. These
      observations suggest that TIMP-2 and TIMP-3 have important but unique roles in
      early cardiac development.

PMID- 11960709
TI  - Expression patterns of aristaless in developing appendages of Gryllus bimaculatus
      (cricket).
AB  - We report the isolation and expression patterns of aristaless (al), a paired-type
      homeobox gene, of Gryllus bimaculatus (Gb), a hemimetabola model insect. Gryllus
      al (Gbal) is expressed in the most distal region of developing labrum, antenna,
      mandible, maxilla, labium, leg, cercus, and hindgut. Gbal is also expressed in
      the proximal region, corresponding to the presumptive coxopodite, of the
      developing antenna, mandible, maxilla, labium, and leg, but not in the developing
      labrum, cercus, and hindgut. During development of the leg, expression of Gbal
      changes dynamically with the progress in leg segmentation: Gbal is expressed in
      order in the presumptive pretarsus, coxa, femur, tibia and tarsus before
      appearance of morphological segmentation.

PMID- 11960711
TI  - Nestin is expressed in mesenchymal and not epithelial cells of the developing
      mouse pancreas.
AB  - Stem cell research and the prospect of stem cell based therapies depend
      critically on the identification of specific markers that can be used for the
      identification and selection of stem and progenitor cells. Nestin is expressed in
      neuronal progenitor cells and has also been suggested to mark multipotent
      pancreatic stem cells. We show here that, throughout pancreatic development,
      markers of pancreatic progenitor cells and differentiated pancreatic cells are
      expressed in E-cadherin-positive epithelial cells that do not express nestin. The
      data presented demonstrate that nestin is expressed in mesenchymal and not
      epithelial cells of the developing mouse pancreas.

PMID- 11960710
TI  - Expression of a novel TGIF subclass homeobox gene, Tex1, in the spermatids of
      mouse testis during spermatogenesis.
AB  - The homeobox gene superfamily is highly conserved during evolution. These genes
      act as transcription factors during several important developmental processes
      through their 60 amino acid homeodomains that recognize and bind to the
      regulatory region of their target genes. We isolated a novel homeobox gene
      designated Tex1 from a mouse testis cDNA library by degenerate oligonucleotide
      polymerase chain reaction (PCR) screening. Three extra amino acid residues, AYP,
      are inserted between the first and second helices of the homeodomain, which makes
      Tex1 a TGIF subclass homeobox gene. Tex1 was expressed specifically in the testis
      as seen by both Northern blot and RT-PCR analysis. Tex1 expression is initiated
      at around day 20 of testes. Furthermore, the results of in situ hybridization
      analysis reveal that the expression of Tex1 in testis is restricted in the germ
      cells at spermatid stage. Based on these data, it is suggested that Tex1, a novel
      testis homeobox gene, may play a crucial role during spermatogenesis.

PMID- 11960712
TI  - Expression of the ERK-specific MAP kinase phosphatase PYST1/MKP3 in mouse embryos
      during morphogenesis and early organogenesis.
AB  - Mitogen-activated-protein kinase (MAP kinase) cascades are effector mechanisms
      for many growth factor signals implicated in developmental processes, including
      appendage outgrowth and organogenesis. The cascade culminates in extracellular
      signal-regulated MAP kinase (ERK), which enters the nucleus. ERK activity
      reflects the competing actions of upstream activator kinases and inhibitory MAP
      kinase phosphatases. We have studied embryonic expression of the dual-specificity
      MAP kinase phosphatase PYST1/MKP3, which is a specific and potent regulator of
      the ERK class of MAP kinases. We found dynamic patterns of mPyst1 messenger RNA
      in important signalling centres associated with cell proliferation and patterning
      in developing mouse embryos, including presegmental paraxial mesoderm, limb bud
      and branchial arch mesenchyme, midbrain/hindbrain isthmus, and nasal, dental,
      hair, and mammary placodes. Most of these have been characterised as sites of
      FGF/FGFR signalling.

PMID- 11960714
TI  - Hoxc12 expression pattern in developing and cycling murine hair follicles.
AB  - We examine the Hoxc12 RNA expression pattern during both hair follicle
      morphogenesis and cycling in direct comparison to its only upstream neighbor,
      Hoxc13. Expression of both genes is restricted to the epidermal part of the
      follicle excluding the outer root sheath and interfollicular epidermis in a
      distinct stage-dependent and cyclical manner. During the progressive growth phase
      (anagen) of developing and cycling follicles, the distinct proximo-distal
      expression domain of Hoxc12 overlaps only proximally, at the upper-most region of
      the bulb, with the more proximally restricted Hoxc13 domain. This arrangement of
      the expression domains of the two genes along the proximal-toward-distal axis of
      increasing follicular differentiation correlates with the sequential expression
      of first Hoxc13 and then Hoxc12. This indicates a reversal of the typical
      temporal colinearity of Hox gene activation otherwise observed along the anterior
      posterior morphogenetic axis of the embryo (review: Cell 78 (1994) 191).

PMID- 11960713
TI  - Gap junctions in Drosophila: developmental expression of the entire innexin gene
      family.
AB  - Invertebrate gap junctions are composed of proteins called innexins and eight
      innexin encoding loci have been identified in the now complete genome sequence of
      Drosophila melanogaster. The intercellular channels formed by these proteins are
      multimeric and previous studies have shown that, in a heterologous expression
      system, homo- and hetero-oligomeric channels can form, each combination
      possessing different gating characteristics. Here we demonstrate that the
      innexins exhibit complex overlapping expression patterns during oogenesis,
      embryogenesis, imaginal wing disc development and central nervous system
      development and show that only certain combinations of innexin oligomerization
      are possible in vivo. This work forms an essential basis for future studies of
      innexin interactions in Drosophila and outlines the potential extent of gap
      junction involvement in development.

PMID- 11960724
TI  - Photofrin as a specific radiosensitizing agent for tumors: studies in comparison
      to other porphyrins, in an experimental in vivo model.
AB  - The use of ionizing radiation for tumor treatment represents a well established
      therapeutic modality. The efficiency and selectivity of radiotherapeutic
      protocols can be often enhanced by the addition of specific chemical compounds
      that optimise the response of the tumor to the incident radiation as compared
      with peritumoral tissue districts. The results of this study showed that
      Photofrin, a porphyrin derivative which is presently used as a tumor
      photosensitizing agent in photodynamic therapy (PDT), can also act as an
      efficient tumor radiosensitizer. To test this possibility, we used nude mice
      subcutaneously implanted with human bladder cancer RT4. The mice were injected
      with different porphyrin-type photosensitizing agents, including Photofrin, 5
      aminolevulinic acid, chlorin e(6), haematoporphyrin, protoporphyrin, Zn
      tetrasulphophtalocyanine, and irradiated with 5 and 15 Gy using a Siemens X-ray
      device. Even though all the porphyrins accumulated in significant amounts in the
      neoplastic lesion, only Photofrin significantly improved the response of the
      tumor to irradiation by increasing the doubling time of the tumor volume from 6.2
      days in the untreated control group to 10.9 days in the 5 and 15 Gy-irradiated
      groups. The tumor response was maximal with injected Photofrin doses of 7.5
      mg/kg, and was not further enhanced by injection of higher doses. Our hypothesis
      is, that the radiosensitizing effect of Photofrin seems to be due to some
      oligomeric constituents which could specifically react with radiogenerated
      radicals thereby amplifying the effect of the X-ray radiation.

PMID- 11960715
TI  - CAP1 expression is developmentally regulated in Xenopus.
AB  - We have cloned and characterized a Xenopus member of the cyclase associated
      protein (CAP) gene family. xCAP1 is expressed as a maternal transcript, but is up
      regulated prior to gastrulation and subsequently localizes to head mesenchyme,
      lens, otic vesicle, and trunk mesoderm including the pronephros. At different
      stages, the gene also appears to differentiate surface from deep (sensorial)
      ectoderm. As in Drosophila, Xenopus CAP1 is expressed in the developing eye,
      specifically in the differentiating lens. However, in distinction to Drosophila,
      Xenopus CAP1 does not express in periodically arrayed neural bands.

PMID- 11960725
TI  - Delayed luminescence from bovine Achilles' tendon and its dependence on collagen
      structure.
AB  - Delayed luminescence from ox Achilles' tendons is found to depend on the order
      parameters of the collagen fibres and on both water content and the temperature,
      which affect those parameters.

PMID- 11960726
TI  - Comparative analysis of foetal calf and human low density lipoprotein: relevance
      for pharmacodynamics of photosensitizers.
AB  - The effects of differences in lipoprotein content on the distribution of the
      novel hydrophobic photosensitizer n-butyl-3-[18-(2-butylcarbamoyl-ethyl)
      3,7,12,17-tetramethyl-18,13-divinyl-22,24-dihydro-porphin-2-yl]propionamide (PP-N
      3) and haematoporphyrin ester (HpE), a relatively hydrophilic photosensitizer, in
      human (HS) and foetal calf sera (FCS), were investigated. The binding
      characteristics of human and foetal calf low-density lipoprotein (LDL) were
      characterised using a human fibroblast line (Vag 12). The uptake into cells of
      HpE and PP-N-3 was also examined. A comparison of the lipoprotein content,
      composition and receptor-binding characteristics of foetal calf and human serum
      was also carried out. LDL content was measured directly using sequential
      ultracentrifugation to isolate LDL. In our study, we found haematoporphyrin ester
      to bind to human very low-density lipoprotein (VLDL), LDL and high-density
      lipoprotein (HDL) in the ratio 2:31:65. In the case of PP-N-3 this ratio was
      56:10:33. As VLDL was not detected in foetal calf serum, only binding to LDL and
      HDL was observed. Using the sequential ultracentrifugation technique, foetal calf
      serum was found to contain LDL which in turn did bind to human LDL receptors. The
      uptake of PP-N-3 and HpE in the presence of low density lipoprotein from foetal
      calf serum (FC-LDL) was not significantly different to values observed in the
      presence of human serum low density lipoprotein (HS-LDL).

PMID- 11960727
TI  - Indications for chlororespiration in relation to light regime in the marine
      diatom Thalassiosira weissflogii.
AB  - The marine diatom Thalassiosira weissflogii was cultured under a light regime
      simulating the daily rise and fall of the sun. The light regime caused a daily
      cycle in non-photochemical quenching. Remarkable were the changes in fluorescence
      directly after a light-to-dark transition that occurred in addition to the
      changes induced by non-photochemical quenching. A transient non-photochemical
      reduction of PQ and of Q(A) was indicated by a transient increase in apparent
      F(o) and by changes in the shape of the fluorescence induction curve. The
      observed changes developed approximately the first 100-120 s after a light-to
      dark transition and could be reversed by the application of far-red illumination.
      Chlororespiration is thought to cause the reduction of PQ and, as the PQ-pool is
      in equilibrium with Q(A), also a reduction of Q(A). The function and ecological
      relevance of chlororespiration are discussed.

PMID- 11960728
TI  - All-trans to 13-cis retinal isomerization in light-adapted bacteriorhodopsin at
      acidic pH.
AB  - The flash photolysis kinetic spectra of the intermediate M(412) of
      bacteriorhodopsin were monitored during the process of acid titration. In the
      light-adapted state, the maximum peak amplitude of M(412) absorbance of
      bacteriorhodopsin decreased (pK(a)=3.40+/-0.05) as the pH decreased from 7.3 to
      1.9. In the dark-adapted state, the maximum peak amplitude of M(412) absorbance
      of bacteriorhodopsin increased as the pH decreased from 6.9 to 4.1, and then
      decreased (pK(a)=2.85+/-0.05) as the pH dropped to 2.1. These different trends in
      the change in the maximum peak amplitude suggested that not only the transition
      of purple membrane to blue membrane had taken place in both light and dark
      adapted states, but also the fraction of all-trans-bR had changed during the acid
      titration. The pH-dependent absorption changes at 640 nm of bacteriorhodopsin in
      both light- and dark-adapted states were also observed. The pK(a)-values of the
      purple-to-blue transition were 3.80+/-0.05 in light-adapted state and 3.40+/-0.05
      in dark-adapted state, respectively. According to Balashov's method, the fraction
      of all-trans-bR was assayed as the pH decreased. All these results indicated that
      the purple-to-blue transition of light-adapted bacteriorhodopsin was accompanied
      by an all-trans to 13-cis retinal isomerization at acidic pH.

PMID- 11960729
TI  - Effect of helium/neon laser irradiation on nerve growth factor synthesis and
      secretion in skeletal muscle cultures.
AB  - Low energy laser irradiation therapy in medicine is widespread but the mechanisms
      are not fully understood. The aim of the present study was to elucidate the
      mechanism by which the light might induce therapeutic effects. Skeletal muscle
      cultures were chosen as a target for light irradiation and nerve growth factor
      (NGF) was the biochemical marker for analysis. It was found that there is a
      transient elevation of intracellular calcium in the myotubes immediately after
      irradiation (P<0.001). Preincubation of the myotubes with either the
      photosensitizers 5-amino-levulinic acid (5-ALA), or with hematoporphyrin (Hp)
      enhanced the elevation of cytosolic calcium (P<0.001) after helium/neon
      irradiation (633 nm) with an energy of 3 J/cm(2). In addition, helium/neon
      irradiation augmented the level of NGF mRNA fivefold and increased NGF release to
      the medium of the myotubes. Thus, it is speculated that transient changes in
      calcium caused by light can modulate NGF release from the myotubes and also
      affect the nerves innervating the muscle. The NGF is probably responsible for the
      beneficial effects of low-level light.

PMID- 11960730
TI  - Photoconductivity of synthetic dopa-melanin polymer.
AB  - The photoconductivity effect in synthetic dopa-melanin polymer with relation to
      the charge hopping conduction has been investigated. Measurements of the rise and
      decay of photocurrents upon visible radiation (400-800 nm) and at temperatures of
      293-326 K allowed the determination of the major trapping levels as follows: 56,
      35 and 26 kJ/mol. Spectral response of the steady-state photocurrent in the range
      367-1100 nm showed significant departures from the absorption spectrum of
      melanin. The high concentration of traps or recombination centers can explain the
      long time-constants calculated from the photocurrent rise and decay curves. The
      results obtained can support the postulated earlier polarons and hopping model of
      conductivity in synthetic dopa-melanin.

PMID- 11960731
TI  - Transient reduction in the tRNA 4-thiouridine content induced by ultraviolet A
      during post-irradiation growth in Enterobacter cloacae.
AB  - The influence of previous exposure to ultraviolet-A radiation (UVA) was studied
      on the susceptibility of Enterobacter cloacae to undergo the growth delay effect.
      Comparison of growth curves corresponding to irradiated and control cells showed
      that a previous treatment with UVA almost abolished the growth delay effect. UV
      absorption spectra of tRNA, and reverse phase HPLC analysis of hydrolysed tRNA,
      demonstrated a low content of 4-thiouridine in E. cloacae cells grown after UVA
      exposure at low doses. Since 4-thiouridine is the UVA target responsible for
      initiation of growth delay, this observation explained the influence of previous
      exposure to UVA on the susceptibility of this organism to undergo growth delay. A
      similar but weaker alteration was found when Escherichia coli was assayed. The
      results suggest that, in addition to cross-linking with cytidine residues, the
      content of 4-thiouridine in tRNA may be modified by UVA by an unknown mechanism.

PMID- 11960732
TI  - Photophysical, photochemical, and thermodynamic properties of shikimic acid
      derivatives: calycin and rhizocarpic acid (lichens).
AB  - Photophysical and photochemical parameters of the lichen metabolites calycin and
      rhizocarpic acid were determined. Experiments were carried out in micellar
      solutions of 3% Brij 35, at pH 2 and 12, and in acetonitrile. Both metabolites
      absorb in the UV-A and UV-B regions, and emit fluorescence in the visible region
      of the solar spectrum. Shifts were not observed in the absorption spectra, at pH
      2 and 12. The low phi(c), between 10(-5) and 10(-2), shows that both compounds
      are photostable in the experimental conditions. For rhizocarpic acid, two values
      of pK(a) were obtained: 5.1 corresponding to the hydroxyl group, and 9.0
      corresponding to the protonated nitrogen. Calycin presents only one value of
      pK(a): 4.9, that is attributed to the hydroxyl group. L-(+)-Gluconic-gamma
      lactonic acid was used as a reference model; the compound showed greater
      photoinstability, demonstrating that the photodegradation observed occurs mainly
      in the oxolane carbonylic ring.

PMID- 11960733
TI  - Effects of potassium halides on bacterial bioluminescence.
AB  - The effects of potassium halides KCl, KBr and KI on NADH:FMN-oxidoreductase
      luciferase bioluminescent coupled enzyme system were studied. The influence of
      salt additions on bioluminescence intensity and bioluminescence light yield was
      investigated. The inhibition and activation parameters of the salts were
      calculated using their dependencies on concentration of the salts. The
      correlation between the inhibition of bioluminescence intensity and the halide
      mass was demonstrated: the inhibiting ability of the salts increases with the
      increase of atomic weight of the anions. The inhibition parameters increase and
      the activation parameters decrease, accordingly.

PMID- 11960735
TI  - A photoprotective role for O(2) as an alternative electron sink in
      photosynthesis?
AB  - Photoprotection of the photosynthetic apparatus has two essential elements:
      first, the thermal dissipation of excess excitation energy in the photosystem II
      antennae (i.e. non-photochemical quenching), and second, the ability of
      photosystem II to transfer electrons to acceptors within the chloroplast (i.e.
      photochemical quenching). Recent studies indicate that the proportion of absorbed
      photons that are thermally dissipated through the non-photochemical pathway often
      reaches a maximum well before saturating irradiances are reached. Hence,
      photochemical quenching is crucial for photoprotection at saturating light
      intensities. When plants are exposed to environmental stresses and the
      availability of CO(2) within the leaf is restricted, the reduction of oxygen by
      both the photorespiratory and the Mehler ascorbate peroxidase pathways appears to
      play a critical photoprotective role, substituting for CO(2) in sustaining
      electron flow. Induction of high activity of the Mehler ascorbate peroxidase
      pathway may be associated with acclimation to environmental stress.

PMID- 11960736
TI  - A plant for all seasons: alterations in photosynthetic carbon metabolism during
      cold acclimation in Arabidopsis.
AB  - Low temperatures lead to the inhibition of sucrose synthesis and photosynthesis.
      The biochemical and physiological adaptations of plants to low temperatures
      include the post-translational activation and increased expression of enzymes of
      the sucrose synthesis pathway, the changed expression of Calvin cycle enzymes,
      and changes in the leaf protein content. Recent progress has been made in
      understanding both the signals that trigger these processes and how the
      regulation of photosynthetic carbon metabolism interacts with other processes
      during cold acclimation.

PMID- 11960737
TI  - Potential impacts of global elevated CO(2) concentrations on plants.
AB  - Early experiments investigating the effects of CO(2) enrichment on plants
      frequently showed photosynthetic stimulation and reduced stomatal aperture over
      short time periods. Work on the effects of elevated CO(2) has advanced in two
      major areas: by the extension of long-term and field experiments, and through
      investigations on the wide range of negative feedbacks affecting plant responses
      to CO(2). Downward photosynthetic acclimation in response to CO(2) enrichment is
      frequently observed over the short and long term, and indicates the activity of
      diverse feedback mechanisms. CO(2) is generally viewed as a limiting
      photosynthetic resource. However, recent work on stomatal development has shown
      that this view is simplistic: long- and short-distance signalling of CO(2)
      concentration are necessary components of normal plant development.

PMID- 11960738
TI  - Plasticity of seed protein composition in response to nitrogen and sulfur
      availability.
AB  - Seed composition is genetically programmed, but the implementation of that
      program is affected by many factors including the nutrition of the parent plant.
      In particular, seeds demonstrate a remarkable capacity to maintain nitrogen
      homeostasis in conditions of varying sulfur supply. They do this by altering the
      expression of individual genes encoding abundant storage proteins. The signal
      transduction pathways that modulate gene expression in seeds in response to N and
      S availability involve both transcriptional and post-transcriptional mechanisms.

PMID- 11960739
TI  - Biosynthesis of flavonoids and effects of stress.
AB  - The accumulation of red or purple flavonoids is a hallmark of plant stress.
      Mounting evidence points to diverse physiological functions for these compounds
      in the stress response. Advances are also being made toward understanding how
      plants control the types and amounts of flavonoids that are produced in response
      to different cues.

PMID- 11960740
TI  - Rewriting the lignin roadmap.
AB  - Considerable interest in lignin biosynthesis has been fueled by the many roles
      that lignin plays in development and in resistance to biotic and abiotic stress,
      as well as its importance to industry and agriculture. Although the pathway
      leading to the lignin polymer has been studied for decades, new insights into the
      enzymes of the pathway have required a complete re-evaluation of how we think
      lignin precursors are synthesized. Although free hydroxycinnamic acids have long
      been thought to be key intermediates, it has become apparent that many of the
      hydroxylation and methylation steps in the pathway occur instead at the level of
      hydroxycinnamic acid esters, and their corresponding aldehydes and alcohols.

PMID- 11960741
TI  - Oxylipin metabolism in response to stress.
AB  - Oxylipins comprise a group of biologically active compounds whose structural
      diversity is generated by the coordinate action of lipases, lipoxygenases, and a
      group of cytochromes P450 that are specialized for the metabolism of hydroperoxy
      fatty acids. Research on oxylipins has focused mainly on the biosynthesis of the
      plant signaling molecule jasmonic acid, and its role in the regulation of
      developmental and defense-related processes. Recent genetic studies indicate that
      metabolic precursors of jasmonate are active as signals in their own right, and
      that the synthesis and perception of jasmonates is critical for wound-induced
      systemic defense responses. Increasing evidence indicates that the collective
      biological importance of oxylipins in plants is comparable to that of the
      eicosanoid family of lipid mediators in animals.

PMID- 11960742
TI  - The formation and function of plant volatiles: perfumes for pollinator attraction
      and defense.
AB  - Plants synthesize and emit a large variety of volatile organic compounds with
      terpenoids and fatty-acid derivatives the dominant classes. Whereas some
      volatiles are probably common to almost all plants, others are specific to only
      one or a few related taxa. The rapid progress in elucidating the biosynthetic
      pathways, enzymes, and genes involved in the formation of plant volatiles allows
      their physiology and function to be rigorously investigated at the molecular and
      biochemical levels. Floral volatiles serve as attractants for species-specific
      pollinators, whereas the volatiles emitted from vegetative parts, especially
      those released after herbivory, appear to protect plants by deterring herbivores
      and by attracting the enemies of herbivores.

PMID- 11960743
TI  - Synthesis and turnover of folates in plants.
AB  - Folates are essential cofactors for one-carbon transfer reactions, which are
      central to plant metabolism. Plants synthesize folates de novo, and are key
      sources of dietary folate for humans. Research into plant folates therefore
      impacts human nutrition. Biochemical progress, the sequencing of the Arabidopsis
      genome, and EST databases are now painting a clear picture of the folate
      synthesis pathway in plants and its surprising compartmentation. Moreover, new
      analytical advances will help to elucidate plant folate turnover and transport,
      which are practically unexplored.

PMID- 11960744
TI  - Enhancement of tolerance of abiotic stress by metabolic engineering of betaines
      and other compatible solutes.
AB  - The accumulation of compatible solutes, such as betaines, proline and sugar
      alcohols, is a widespread response that may protect plants against environmental
      stress. It is not yet fully understood how these compounds are involved in the
      stress tolerance of whole plants. Some plants have been genetically engineered to
      express enzymes that catalyze the synthesis of various compatible solutes. Some
      interventions have increased the tolerance of some crop plants to abiotic stress.
      Furthermore, analysis of such transgenic plants has begun to clarify the roles of
      compatible solutes in stress tolerance.

PMID- 11960745
TI  - Plants in space.
AB  - Virtually all scenarios for the long-term habitation of spacecraft and other
      extraterrestrial structures involve plants as important parts of the contained
      environment that would support humans. Recent experiments have identified several
      effects of spaceflight on plants that will need to be more fully understood
      before plant-based life support can become a reality. The International Space
      Station (ISS) is the focus for the newest phase of space-based research, which
      should solve some of the mysteries of how spaceflight affects plant growth.
      Research carried out on the ISS and in the proposed terrestrial facility for
      Advanced Life Support testing will bring the requirements for establishing
      extraterrestrial plant-based life support systems into clearer focus.

PMID- 11960746
TI  - A novel lipid compound, epolactaene, induces apoptosis: its action is modulated
      by its side chain structure.
AB  - A novel lipid compound, epolactaene, was isolated from the culture supernatant of
      Penicillium sp. 1689-P and it has already been reported that it induced neurite
      outgrowth in a human neuroblastoma cell line. In this study, we first
      investigated the effects of epolactaene on a human leukemia B-cell line, BALL-1
      cells, and clarified that epolactaene induces apoptosis in BALL-1 cells in a dose
      and time-dependent manner. Furthermore, we focused on the side chain structure
      of epolactaene, and chemically synthesized epolactaene derivatives. One
      derivative, which has a straight long alkyl chain as its side chain, induced
      apoptosis more effectively than epolactaene. On the other hand, other derivatives
      with a short alkyl side chain had weaker apoptosis-inducing actions. A good
      correlation was found between the apoptosis-inducing action of these compounds
      and their octanol/water partition coefficients (log P). These results suggested
      that the apoptosis-inducing activities of epolactaene and its derivatives were
      related to the hydrophobicity of these compounds; so that side chain structure of
      epolactaene is very important for its apoptosis-inducing activities. These
      apoptosis-inducing actions of epolactaene and its derivatives were also observed
      in various blood tumor cell lines and normal lymphocytes.

PMID- 11960747
TI  - Incorporation of semi-fluorinated alkanes in the bilayer of small unilamellar
      vesicles of phosphatidylserine: impact on fusion kinetics.
AB  - Semi-fluorinated alkanes C(n)F(2n+1)C(m)H(2m+1) (FnHm) can be co-dispersed with
      standard phospholipids to form 'fluorinated' vesicles, i.e. vesicles with an
      internal fluorinated film within their bilayer membrane. This paper reports the
      effect of the presence of such FnHm diblocks in phosphatidylserine (PS)-based
      small unilamellar vesicles (SUVs) on their kinetics of fusion. Fusion was induced
      by calcium ions and monitored by the terbium/dipicolinic acid assay. The diblocks
      were composed of a 10-carbon long linear hydrocarbon segment and of a linear
      fluorocarbon segment of four, six or eight carbon atoms. We found that the
      incorporation of FnHm in the PS membrane considerably modifies the kinetics of
      the process of fusion, with Ca(2+) concentration having a much more limited
      effect on the fluorinated vesicles. Both the rates of fusion and the rates of
      release of the internal content, as evaluated by the release of 5,6
      carboxyfluorescein, were much lower for the fluorinated SUVs than for those based
      on phosphatidylserine alone, the highest effect being obtained for F6H10 with a
      10 times slower rate of fusion and a 40-fold reduction in the release of content.
      FnHm molecules are proposed to have a dual action: by hindering fusion and
      release by creating an inert, hydrophobic and lipophobic fluorinated film in the
      core of the membrane, and by stabilizing the membrane by increasing van der Waals
      interactions in the hydrocarbon region.

PMID- 11960748
TI  - Inhibition of the plastidial phosphatidylcholine synthesis by silver, copper,
      lead and mercury induced by formation of mercaptides with the lyso-PC
      acyltransferase.
AB  - Plastids greatly rely on the import of extraplastidial precursors for the
      synthesis of their own lipids, and several studies have shown that a lyso-PC
      acyltransferase located in the envelope may be involved in the import process.
      Because the presence of heavy metals in soil or in nutrient solutions induces
      changes in the lipid composition of plastid membranes (and therefore greatly
      reduces the photosynthetic capability of plants), we analysed the effect of
      several metal salts on plastidial lyso-PC acyltransferase activity. Among the 12
      heavy metals studied, silver, copper, mercury and lead inhibited this activity.
      Metal bound to the enzyme was not - or only very slightly - released from the
      protein except when thiol-reducing agents (and not imidazole) were added. The
      results strongly suggest that the inhibitory effect is due to a formation of
      mercaptide between metal and cysteine(s). The relationship between the inhibition
      of the plastidial lyso-PC acyltransferase activity and the in vivo effects of
      metal salts on the plastid membranes is discussed.

PMID- 11960749
TI  - Beta-D-glucopyranosyl caldarchaetidylglycerol is the main lipid of the
      acidophilic, mesophilic, ferrous iron-oxidising archaeon Ferroplasma acidiphilum.
AB  - Chloroform-methanol-extractable lipids account for about 5% by weight of dry
      cells of the acidophilic, autotrophic, mesophilic, ferrous compound-oxidising,
      cell wall-less archaeon Ferroplasma acidiphilum strain Y(T), about 90% of these
      being contributed by phospholipids and glycophospholipids. The most abundant
      constituent (about 55% of total lipids) was purified by DEAE cellulose and silica
      gel column chromatography. By means of matrix-assisted laser desorption
      ionisation mass spectrometry, infrared spectroscopy, (1)H-nuclear magnetic
      resonance spectroscopy, and chemical degradation experiments it was established
      to be beta-D-glucopyranosyl caldarchaetidylglycerol, the isopranyl chains of
      which have a cyclopentane ring each.

PMID- 11960750
TI  - Dexamethasone stimulates very low density lipoprotein (VLDL) receptor gene
      expression in differentiating 3T3-L1 cells.
AB  - To characterize endocrine mechanisms of very low density lipoprotein (VLDL)
      receptor regulation we studied mouse adipocytic 3T3-L1 cells. Lipid filled
      adipocyte-like cells are formed during a 5-7 day time course in the presence of
      insulin, dexamethasone and isobutylmethylxanthine (IBMX). The VLDL receptor
      protein, in the form of its approximately 120 and approximately 100 kDa type I
      and type II isoforms, as well as binding of (125)I-beta-VLDL, was induced several
      fold during differentiation. Among the three different constituents added to the
      culture medium only dexamethasone (1 microM), but not insulin or IBMX, induced a
      time- and dose-dependent increase of VLDL receptor expression. Inclusion of RU
      486 (10 microM) blocked the stimulatory effect of dexamethasone on VLDL receptor
      mRNA and protein levels. 3.6 kb of the 5'-untranslated region representing the
      VLDL receptor promoter were cloned and sequenced, and the transcriptional start
      site was determined by primer extension to be located 574 bases upstream from the
      initiating methionine. To investigate the functionality of the promoter,
      luciferase reporter gene constructs for the region -181 to -3726 bases were
      assembled and transfected into 3T3-L1 cells. An increased reporter gene activity
      was recorded when comparing preconfluent cells to fully differentiated cells.
      Between day 0 and day 2 (48 h after transfection) reporter gene activity was
      induced by dexamethasone, but not by insulin or IBMX. RU-486 inhibited this
      stimulatory effect for all constructs tested. No classical glucocorticoid
      receptor (GR) response element was found in the sequenced region of the VLDL
      receptor promoter. Thus, an indirect stimulatory effect mediated via GR on VLDL
      receptor gene transcription is the most likely mechanism of VLDL receptor gene
      activation in differentiating 3T3-L1 cells.

PMID- 11960751
TI  - Overexpression of PEMT2 downregulates the PI3K/Akt signaling pathway in rat
      hepatoma cells.
AB  - Phosphatidylethanolamine N-methyltransferase 2 (PEMT2) is an isoform of PEMT that
      converts phosphatidylethanolamine to phosphatidylcholine in mammalian liver.
      Overexpression of PEMT2 led to inhibition of proliferation of hepatoma cells [J.
      Biol. Chem. 269 (1994) 24531]. The present study aims to unravel the molecular
      mechanism of the reduced proliferation, especially the signaling transducer
      proteins involved in this process. Thus, we chose PI3K/Akt pathway that is
      initiated by growth factors and leads to cell survival and proliferation. Rat
      hepatoma CBRH-7919 cells transfected with pemt2-cDNA showed that: (1) signaling
      proteins including c-Met, PDGF receptor, PI3K, Akt and Bcl-2 all had reduced
      expression as shown by Western blotting studies; (2) flow cytometric and DNA
      ladder assays showed that 22.9% of the pemt2-transfected cells were undergoing
      apoptosis; (3) the activity of Akt was decreased as shown by Western blotting
      using antibody directed against p-Akt (Thr308); (4) wortmannin and PD98059,
      inhibitors of PI3K and MEK, respectively, both inhibited Akt activity, indicating
      that PI3K and MAPK pathways were merging at Akt in CBRH-7919 cells. The above
      results suggest that overexpression of PEMT2 strongly downregulated the PI3K/Akt
      signaling pathway at multiple sites and induced apoptosis. This, at least partly,
      explains the molecular mechanism of impaired proliferation induced by pemt2
      transfection.

PMID- 11960752
TI  - Effect of acetaminophen on the myeloperoxidase-hydrogen peroxide-nitrite mediated
      oxidation of LDL.
AB  - Myeloperoxidase, in the presence of hydrogen peroxide and nitrite, promotes the
      lipid peroxidation of low density lipoprotein (LDL); the modified lipoprotein is
      then capable of being readily endocytosed by macrophages. Since acetaminophen has
      been shown to inhibit the leukocyte myeloperoxidase antimicrobial system and is,
      under certain experimental conditions, an antioxidant, the effect of
      acetaminophen on the myeloperoxidase-hydrogen peroxide-nitrite mediated oxidation
      of LDL was examined. The content of LDL lipid hydroperoxides after incubation
      with 50 nM myeloperoxidase, 100 microM nitrite and a hydrogen peroxide generating
      system for 6 h was reduced by approx. 80% in the presence of 25-250 microM
      acetaminophen. The production of thiobarbituric acid-reactive substances was also
      inhibited by acetaminophen to a similar extent. Acetylsalicylic acid (25-100
      microM) did not inhibit LDL lipid peroxidation mediated by the myeloperoxidase
      enzyme system. LDL, treated with myeloperoxidase, hydrogen peroxide and nitrite
      for 14 h, was metabolized by macrophages to a much greater extent than native
      LDL. The presence of acetaminophen prevented the modification of LDL; the
      lipoprotein was metabolized by macrophages to the same extent as was native LDL.
      These results demonstrate that acetaminophen is a potent inhibitor of the
      myeloperoxidase-hydrogen peroxide-nitrite mediated modification of LDL.

PMID- 11960753
TI  - Expression of genes encoding chalcone synthase, flavanone 3-hydroxylase and
      dihydroflavonol 4-reductase correlates with flavanol accumulation during
      heartwood formation in Juglans nigra.
AB  - Heartwood formation is generally characterized by the accumulation of phenolic
      substances that increase the natural color and durability of wood. Although there
      is evidence that these substances are synthesized in aging sapwood cells, little
      is known about heartwood formation at the molecular level. We monitored seasonal
      changes in flavanol concentration across the stems of 23-year-old Juglans nigra
      L. trees by sampling growth rings extending from the differentiating xylem to the
      heartwood. We also analyzed expression of phenylpropanoid and flavonoid
      structural genes in these samples. In the sapwood-heartwood transition zone,
      flavanol accumulation was correlated with the transcription levels of the
      chalcone synthase (CHS) and flavanone 3-hydroxylase (F3H) genes. We also observed
      correlations between flavanol accumulation and the amount of dihydroflavonol 4
      reductase (DFR) gene transcript in October, January and May. Although
      transcription of phenylalanine ammonia-lyase (PAL) and 4-coumarate:CoA ligase
      (4CL) genes did not correlate with flavanol accumulation, PAL genes were strongly
      expressed in the transition zone of samples collected in autumn, suggesting that
      their transcription in these tissues contributes to phenolic biosynthesis.
      Western immunoblotting showed that accumulation of CHS protein correlated with
      the amount of CHS gene transcript, whereas accumulation of PAL protein did not
      correlate with the the transcription levels PAL genes. Preliminary analyses
      revealed that PAL and CHS activities were higher in the transition zone than in
      the inner sapwood in autumn, winter, and spring. Thus, CHS activity could be
      regulated mainly at the transcriptional level, whereas post-translational
      modifications could modulate PAL activity. We conclude that flavanols are
      synthesized de novo in J. nigra sapwood cells that are undergoing transformation
      to heartwood.

PMID- 11960754
TI  - SAGE profiling and demonstration of differential gene expression along the axial
      developmental gradient of lignifying xylem in loblolly pine (Pinus taeda).
AB  - Wood formation has been studied extensively at the cellular and biochemical
      levels, but remains poorly understood with respect to gene expression and
      regulation. As a first step toward identifying genes specifically involved in
      wood formation and characterizing their roles in determining wood quality, serial
      analysis of gene expression (SAGE) was used to quantify gene expression in
      lignifying xylem from a single, 10-year-old loblolly pine (Pinus taeda L.). Two
      SAGE libraries were generated based on lignifying xylem isolated from either the
      upper (crown) or lower (base) portions of the trunk. Over 85,000 tags
      representing a maximum of 27,398 expressed genes were analyzed from the crown
      wood library, and more than 65,000 tags, representing a maximum of 25,983
      expressed genes, were analyzed in the base wood library. Combining these data
      sets to reflect the sum of genes expressed in lignifying xylem, 150,855 tags were
      cataloged, representing a maximum of 42,641 different genes. Currently, this
      study represents the most extensive analysis of its kind in a higher plant and
      provides a quantitative description of the transcriptome representing the
      lignifying xylem of a 10-year-old loblolly pine.

PMID- 11960755
TI  - Gravimorphism in current-year shoots of Abies balsamea: involvement of
      compensatory growth, indole-3-acetic acid transport and compression wood
      formation.
AB  - We investigated the cause of gravimorphic growth inhibition in current-year
      shoots of balsam fir (Abies balsamea (L.) Mill.) seedlings displaced from their
      normal orientation in the gravitational field. Tilting the main stem of seedlings
      decreased shoot elongation, cambial growth as measured by tracheid production,
      and leaf dry weight of the terminal shoot and the lateral shoots on the lower
      side of the tilted stem. Removing either the terminal shoot or all lateral shoots
      induced compensatory growth in the remaining shoots, but did not reduce the
      inhibitory effect of tilting on shoot growth. Bending the apical part of a tilted
      main stem to restore it to the vertical did not fully reverse the inhibition of
      terminal shoot growth caused by stem tilting. Stem tilting inhibited cambial
      activity at the base of decapitated terminal shoots treated apically with indole
      3-acetic acid (IAA) and decreased the basipetal transport of a [1-(14)C]-IAA
      pulse. Stem tilting also induced compression wood formation on the lower side of
      the tilted stem. Compression wood formation was associated with increases in
      cambial activity and stem respiration. Stem tilting did not affect either the net
      photosynthetic rate in 1-year-old leaves or the xylem water potential in current
      year lateral shoots. These results support the hypothesis that gravimorphic
      growth inhibition in a current-year shoot on a tilted stem involves reductions in
      (1) the shoot's capacity to export IAA, and hence to mobilize photoassimilates,
      and (2) the supply of photoassimilates available for import by the shoot, as a
      result of increased cambial sink activity associated with compression wood
      formation outside that shoot.

PMID- 11960756
TI  - Photosynthetic acclimation of overstory Populus tremuloides and understory Acer
      saccharum to elevated atmospheric CO2 concentration: interactions with shade and
      soil nitrogen.
AB  - We exposed Populus tremuloides Michx. and Acer saccharum Marsh. to a factorial
      combination of ambient and elevated atmospheric CO2 concentrations ([CO2]) and
      high-nitrogen (N) and low-N soil treatments in open-top chambers for 3 years. Our
      objective was to compare photosynthetic acclimation to elevated [CO2] between
      species of contrasting shade tolerance, and to determine if soil N or shading
      modify the acclimation response. Sun and shade leaf responses to elevated [CO2]
      and soil N were compared between upper and lower canopy leaves of P. tremuloides
      and between A. saccharum seedlings grown with and without shading by P.
      tremuloides. Both species had higher leaf N concentrations and photosynthetic
      rates in high-N soil than in low-N soil, and these characteristics were higher
      for P. tremuloides than for A. saccharum. Electron transport capacity (Jmax) and
      carboxylation capacity (Vcmax) generally decreased with atmospheric CO2
      enrichment in all 3 years of the experiment, but there was no evidence that
      elevated [CO2] altered the relationship between them. On a leaf area basis, both
      Jmax and Vcmax acclimated to elevated [CO2] more strongly in shade leaves than in
      sun leaves of P. tremuloides. However, the apparent [CO2] x shade interaction was
      largely driven by differences in specific leaf area (m2 g-1) between sun and
      shade leaves. In A. saccharum, photosynthesis acclimated more strongly to
      elevated [CO2] in sun leaves than in shade leaves on both leaf area and mass
      bases. We conclude that trees rooted freely in the ground can exhibit
      photosynthetic acclimation to elevated [CO2], and the response may be modified by
      light environment. The hypothesis that photosynthesis acclimates more completely
      to elevated [CO2] in shade-tolerant species than in shade-intolerant species was
      not supported.

PMID- 11960757
TI  - Induction of discolored wood in Scots pine (Pinus sylvestris).
AB  - Induction of discolored wood in Scots pine (Pinus sylvestris L.) trees by
      treatment with ethylene, carbon dioxide, nitrogen (hypoxia) or wounding from
      early April to late September was investigated. All treatments induced formation
      of discolored wood upward and downward from the drill hole. The amount of
      discolored wood formed above the drill hole depended on the treatment in the
      following order: ethylene > carbon dioxide = nitrogen > wounding; and below the
      drill hole in the order: ethylene > carbon dioxide = nitrogen = wounding. Based
      on chemical analyses (HPLC/UV, GS/MS, LC/MS and 1H-NMR), discolored wood induced
      by wounding or treatment with ethylene or carbon dioxide showed compositional
      similarities to natural heartwood, whereas discolored wood induced by nitrogen
      treatment showed fewer similarities to natural heartwood. The results suggest
      that ethylene is an important factor controlling heartwood formation, although
      wounding and internal concentrations of carbon dioxide may also play a role.

PMID- 11960758
TI  - Responses of Acer negundo genders to interannual differences in water
      availability determined from carbon isotope ratios of tree ring cellulose.
AB  - Understanding the responses of riparian trees to water availability is critical
      for predicting the effects of changes in precipitation on riparian ecosystems.
      Dioecious Acer negundo L. (box elder) is a common riparian tree that is highly
      sensitive to water stress. Earlier studies indicated that the genders of A.
      negundo respond differently to water availability, with males being more
      conservative in their water use than females. To assess the potential effects of
      changes in precipitation on the sex ratio of riparian trees, we extended earlier
      studies of A. negundo by analyzing responses of male and female genotypes to
      interannual differences in water availability in a common garden. We measured
      growth of tree rings and used stable carbon isotope analysis of tree ring alpha
      cellulose to integrate physiological responses to annual water treatments. During
      dry years, male and female trees exhibited similar growth and physiological
      responses. However, during wet years, females exhibited higher growth rates and
      lower carbon isotope ratios (indicating less conservative water use) than did
      males. Furthermore, we found that male trees exhibited similar stomatal behavior
      (inferred from integrated carbon isotope ratios) whether years were wet or dry,
      whereas females did not exhibit a consistent response to changes in water
      availability. We predict that with increasing precipitation and soil water
      availability, the representation of females will be favored because of shifts in
      the competitive interactions of the genders. Such changes may affect the
      reproductive output of these riparian trees and may influence overall water flux
      from riparian ecosystems. In addition, this study demonstrates the utility of
      carbon isotope analysis for assessing long-term responses of tree populations to
      shifts in water availability.

PMID- 11960759
TI  - Effects of phloem girdling in conifers on apical control of branches, growth
      allocation and air in wood.
AB  - We investigated effects of stem phloem girdles on apical control of branch angle,
      stem and branch growth and stem air content in six conifer species. A stem girdle
      2 cm above a branch caused the branch to bend upward in all six species. Upward
      bending was associated with increased formation and action of compression wood
      (CW) in the lower portion of the branch. Compression wood also formed in the main
      stem below the branch, suggesting increased auxin production in the branch. A
      stem girdle 2 cm below a branch (the branch remained directly connected to the
      apex and distal branches) released the branch from apical control in Tsuga
      canadensis (L.) Carr., Pinus contorta Dougl. ex Loud. and Pseudotsuga menziesii
      (Mirb.) Franco. The branch bent up, but there was no CW formation in the stem. In
      Pinus rigida Mill., the branch exhibited increased cambial activity but did not
      bend up. A stem girdle > 20 cm below a branch did not release the branch from
      apical control in any of the species. These results support the hypothesis that
      branches compete with the subjacent stem for branch-produced photosynthate and
      that when the branch lacks this competitive sink it is released from apical
      control. A stem girdle 2 cm below a branch did not cause release of apical
      control in either Juniperus virginiana L. or Picea abies (L.) Karst. In these
      species, decreased shoot elongation and cambial activity above the girdle
      probably prevented release. A stem girdle 2 cm below a branch increased air
      content in the stem below the girdle in four of five species, whereas the other
      girdle treatments had no significant effect on stem air content. Although growth
      was inhibited above the girdle in the two species with the largest increase in
      air content, growth was not inhibited in the other species. High air content in
      stem segments isolated from distal auxin and carbohydrate sources is consistent
      with the hypothesis that a carbohydrate supply is required to refill embolized
      cells.

PMID- 11960760
TI  - Ecophysiological characteristics of Taiwan alder (Alnus formosana) seedlings
      adapted to the subtropical region.
AB  - We investigated several ecophysiological characteristics of seedlings of a low
      elevation (100-200 m) and a high-elevation (2000-2400 m) population of Taiwan
      alder (Alnus formosana Makino) from subtropical Taiwan. Both populations had a
      wide optimal temperature range for photosynthesis, and there was little
      difference in the optimal temperature range for photosynthesis between
      populations. Photosynthetic rate (P(N)) was near maximal from 20 to 35 degrees C
      when seedlings of both the low-elevation and the high-elevation populations were
      acclimated at a day/night temperature of 30/23 degrees C. When seedlings were
      acclimated at a day/night temperature of 20/10 degrees C, P(N) was near maximal
      over the range 15-35 degrees C in the low-elevation population and 15-30 degrees
      C in the high-elevation population. Compared with nine other tree species native
      to Taiwan, Taiwan alder had a high P(N) and stomatal conductance (g(s)) under
      well-watered conditions. Reflecting its higher transpiration rate, Taiwan alder
      had a significantly greater leaf-air temperature difference than camphor
      (Cinnamomum camphora (L.) J. Presl), a co-occurring lowland tree species with
      leaves similar in shape and size to those of Taiwan alder. Despite higher g(s),
      high root and shoot hydraulic conductances enabled Taiwan alder to maintain
      higher leaf water potentials than camphor under well-watered conditions. We
      conclude that both photosynthetic characteristics and water relations are
      important factors enabling Taiwan alder to adapt to a wide temperature range,
      thereby ensuring its success at both high and low elevations in subtropical
      Taiwan.

PMID- 11960761
TI  - Responses of transpiration and photosynthesis to reversible changes in
      photosynthetic foliage area in western red cedar (Thuja plicata) seedlings.
AB  - Experiments were conducted on 1-year-old western red cedar (Thuja plicata Donn.)
      seedlings to determine the response of illuminated foliage to reversible changes
      in total photosynthetic foliage area (L(A)). Reductions in L(A) were brought
      about by either shading the lower foliage or by reducing the ambient CO2
      concentration (c(a)) of the air surrounding the lower part of the seedling. In
      the latter case, the vapor pressure was also changed so that transpiration rates
      (E) could be manipulated independently of photosynthetic rates (A). We
      hypothesized that following such treatments, short-term compensatory changes
      would occur in stomatal conductance (g(s)) and A of the remaining foliage. These
      changes would occur in response to hydraulic signals generated by changes in the
      water potential gradient rather than changes in the distribution of sources and
      sinks of carbon within the seedling. When a portion of the foliage was shaded,
      there was an immediate reduction in whole-seedling E and a concomitant increase
      in g(s), A and E in the remaining illuminated foliage. However, the intercellular
      CO2 concentration did not change. These compensatory effects were fully reversed
      after the shade was removed. When the lower foliage A was reduced to < 0 micromol
      m-2 s-1, by shading or lowering c(a), and E was either unchanged or increased (by
      adjusting the vapor pressure deficit), there was no significant increase in g(s)
      and A in the remaining foliage. We conclude that compensatory responses in
      illuminated foliage occur only when reductions in L(A) are accompanied by a
      reduction in whole-plant E. The relationship between the reduction in whole
      seedling E and the increase in A is highly linear (r2 = 0.68) and confirms our
      hypothesis of the strong regulation of g(s) by hydraulic signals generated within
      the seedling. We suggest that the mechanism of the compensatory effects is a
      combination of both increased CO2 supply, resulting from increased g(s), and a
      response of the rate of carboxylation, possibly related to the activity of
      Rubisco.

PMID- 11960762
TI  - Effects of exogenous diamines on the interaction between ectomycorrhizal fungi
      and adventitious root formation in Scots pine in vitro.
AB  - Production of free and conjugated polyamines by two ectomycorrhizal fungi,
      Pisolithus tinctorius (Pers.) Coker and Couch and Paxillus involutus (Batsch)
      Fr., was studied in vitro. Spermidine was the main polyamine in the mycelium of
      both fungi. Paxillus involutus also produced large amounts of the diamine
      putrescine, whereas Pisolithus tinctorius contained traces of the diamine
      cadaverine and released into the culture medium an unknown compound probably
      related to cadaverine or N-methylputrescine. Both fungi accelerated adventitious
      root formation and increased subsequent root growth of Scots pine (Pinus
      sylvestris L.) hypocotyl cuttings in vitro. Exogenous cadaverine enhanced rooting
      caused by Pisolithus tinctorius and also promoted mycorrhiza formation by the
      fungus. Putrescine and Paxillus involutus had a synergistic effect on root
      initiation, but not on subsequent root growth. We conclude that specific diamines
      may be involved in the interaction between ectomycorrhizal fungi and adventitious
      root formation in Scots pine, and that the effects of specific exogenous
      polyamines are dependent on the fungal strain and its ability to produce these
      compounds. The finding that Paxillus involutus enhanced rooting and root growth
      without mycorrhiza formation indicates that fungal-induced rooting is not
      necessarily related to visible mycorrhiza formation.

PMID- 11960763
TI  - Growth rate and survivorship of drought: CO2 effects on the presumed tradeoff in
      seedlings of five woody legumes.
AB  - Traits that promote rapid growth and seedling recruitment when water is plentiful
      may become a liability when seedlings encounter drought. We tested the hypothesis
      that CO2 enrichment reinforces any tradeoff between growth rate and drought
      tolerance by exaggerating interspecific differences in maximum relative growth
      rate (RGR) and survivorship of drought among seedlings of five woody legumes. We
      studied invasive species of grasslands that differ in distribution along a
      rainfall gradient. Survivorship of drought at ambient CO2 concentration ([CO2])
      was negatively related to RGR in well-watered seedlings in one of two
      experiments, but the relationship was weak because interspecific differences in
      RGR were small. Contrary to our hypothesis, there was no significant relationship
      among well-watered seedlings between RGR at ambient [CO2] and either the relative
      or absolute increase in RGR at elevated [CO2]. As predicted, however, CO2
      enrichment reinforced interspecific differences in survivorship of seedlings
      exposed to similar rates of soil water depletion. Doubling [CO2] improved
      seedling survivorship of the most drought-tolerant species throughout the period
      of soil water depletion, but did not consistently affect survivorship of more
      drought-sensitive species. Midday xylem pressure potentials of drought-treated
      seedlings were less negative at elevated [CO2] than at ambient [CO2], but no
      other measured trait was consistently correlated with improved survivorship at
      high [CO2]. Carbon dioxide enrichment may not reinforce species differences in
      RGR, but could exaggerate interspecific differences in drought tolerance. To the
      extent that seedling persistence in grasslands correlates with drought
      survivorship, our results indicate a positive effect of CO2 enrichment on
      recruitment of woody legumes that are currently tolerant of drought.

PMID- 11960764
TI  - Short-term light and leaf photosynthetic dynamics affect estimates of daily
      understory photosynthesis in four tree species.
AB  - Instantaneous measurements of photosynthesis are often implicitly or explicitly
      scaled to longer time frames to provide an understanding of plant performance in
      a given environment. For plants growing in a forest understory, results from
      photosynthetic light response curves in conjunction with diurnal light data are
      frequently extrapolated to daily photosynthesis (A(day)), ignoring dynamic
      photosynthetic responses to light. In this study, we evaluated the importance of
      two factors on A(day) estimates: dynamic physiological responses to
      photosynthetic photon flux density (PPFD); and time-resolution of the PPFD data
      used for modeling. We used a dynamic photosynthesis model to investigate how
      these factors interact with species-specific photosynthetic traits, forest type,
      and sky conditions to affect the accuracy of A(day) predictions. Increasing time
      averaging of PPFD significantly increased the relative overestimation of A(day)
      similarly for all study species because of the nonlinear response of
      photosynthesis to PPFD (15% with 5-min PPFD means). Depending on the light
      environment characteristics and species-specific dynamic responses to PPFD,
      understory tree A(day) can be overestimated by 6-42% for the study species by
      ignoring these dynamics. Although these overestimates decrease under cloudy
      conditions where direct sunlight and consequently understory sunfleck radiation
      is reduced, they are still significant. Within a species, overestimation of
      A(day) as a result of ignoring dynamic responses was highly dependent on daily
      sunfleck PPFD and the frequency and irradiance of sunflecks. Overall, large
      overestimates of A(day) in understory trees may cause misleading inferences
      concerning species growth and competition in forest understories with < 2% full
      sunlight. We conclude that comparisons of A(day) among co-occurring understory
      species in deep shade will be enhanced by consideration of sunflecks by using
      high-resolution PPFD data and understanding the physiological responses to
      sunfleck variation.

PMID- 11960765
TI  - Gas exchange, water relations and osmotic adjustment in Phillyrea latifolia grown
      at various salinity concentrations.
AB  - Leaf gas exchange, water relations and osmotic adjustment were studied in
      hydroponically grown Phillyrea latifolia L. plants exposed to 5 weeks of salinity
      stress (0, 80, 160, 240 and 320 mM NaCl) followed by 5 weeks of treatment with
      half-strength Hoagland solution. Whole-plant relative growth rate and root/shoot
      and lateral/structural root ratios were also evaluated. Net CO2 assimilation
      rate, stomatal conductance and transpiration rate were markedly decreased by all
      of the salt treatments. Growth was also strongly depressed by all salt
      treatments, especially lateral root growth. Leaf water potential decreased soon
      after salinity stress was imposed, whereas there was a lag of several weeks
      before leaf osmotic potential decreased in response to the salt treatments. After
      5 weeks of salinization, leaf turgor of salt-treated plants was similar to that
      of controls. Although Na+ + Cl- contributed little to the salt-induced changes in
      osmotic potential at full turgor (Psi(piFT)), the contributions of K+, mannitol
      (Man) and glucose (Glc) to Psi(piFT) markedly increased as external salinity
      increased. Salt accumulation was negligible in the youngest leaves, which mostly
      accumulated soluble carbohydrates and K+; in contrast, old leaves served as
      storage sinks for Na+ and Cl-. Photosynthetic performance of salt-treated plants
      fully recovered once salt was leached from the root zone, with the recovery rate
      depending on the severity of the salt stress previously experienced by the
      plants. Recovery of gas exchange occurred even though the leaves still had a salt
      load similar to that detected in leaves at the end of the 5-week salinity period,
      and had markedly lower concentrations of K+ and soluble carbohydrates than
      control leaves. We conclude that salt-induced water stress primarily controlled
      gas exchange of salt-treated P. latifolia leaves, whereas the salt load in the
      leaves did not cause irreversible damage to the photosynthetic apparatus.

PMID- 11960766
TI  - Comparison of water-use efficiency of seedlings from two sympatric oak species:
      genotype x environment interactions.
AB  - Seedlings of two sympatric oak species, Quercus robur L. and Quercus petraea
      (Matt.) Liebl., were grown in common garden conditions to test for potential
      interspecific differences in intrinsic water-use efficiency (WUE). Intrinsic
      water-use efficiency was estimated based on carbon isotope composition of shoots
      (delta13C) and on gas exchange measurements (ratio of net CO2 assimilation rate
      to stomatal conductance (A/g(sw))). In addition, genotype x environment
      interactions were tested by subjecting the seedlings to four irradiance
      treatments (8, 18, 48 and 100% of incident solar irradiance) imposed by neutral
      shading nets, and, in the 100% irradiance treatment, two watering regimes. In all
      treatments, initial growth of Q. robur was faster than that of Q. petraea. In
      both species, there was a tight correlation between delta13C and A/g(sw).
      Intrinsic water-use efficiency increased with increasing irradiance (almost
      doubling from 8 to 100% irradiance), and this effect paralleled the increase in A
      with increasing irradiance. In full sun, WUE of Q. petraea seedlings was 10-15%
      higher than in Q. robur seedlings, with the difference attributable to a
      difference between the species in g(sw). The interspecific difference in WUE was
      maintained during drought, despite the appreciable increase in WUE and decrease
      in growth imposed by drought. No interspecific differences in WUE were observed
      at low irradiances, suggesting a strong genotype x environment interaction for
      WUE. These findings confirm the existence of interspecific genetic differences in
      WUE, but also show that there is large intraspecific variability and plasticity
      in WUE. The initially greater height and biomass increments in Q. robur seedlings
      illustrate the ability of this species to out-compete Q. petraea in the early
      stages of forest regeneration. For adult trees growing in closed canopies, the
      high WUE of Q. petraea may contribute significantly to its survival during dry
      years, whereas the low WUE of Q. robur may account for the frequently observed
      declines in adult trees of this species following drought.

PMID- 11960767
TI  - Seasonal regulation of a 24-kDa protein from red-osier dogwood (Cornus sericea)
      xylem.
AB  - Previously, we showed that an apparent cell wall-plasma membrane interaction in
      xylem ray parenchyma differed between cold acclimated and non-acclimated red
      osier dogwood (Cornus sericea L.) (Ristic and Ashworth 1994). For the present
      study, a calcium chloride extraction method was used to identify cell-wall
      associated xylem proteins that accumulated during periods of cold acclimation. A
      24-kDa protein represented the predominant protein in both total protein and
      CaCl2 extracts during cold acclimation of field-grown plants. Two-dimensional gel
      electrophoresis separated the 24-kDa protein into four basic isoforms. The most
      abundant and basic isoform had a high glycine content. In-gel digestion of this
      basic 24-kDa isoform generated three partial peptide fragments, of which one
      exhibited homology to the dehydrin protein family. An anti-dehydrin polyclonal
      antibody cross-reacted with the 24-kDa protein, providing further evidence that
      this protein is related to dehydrins. The 24-kDa protein began to accumulate in
      late August, reached a maximum in midwinter, declined during the spring months
      and was absent in early summer.

PMID- 11960768
TI  - Charcoal affects early development and hormonal concentrations of somatic embryos
      of hybrid larch.
AB  - Embryogenic tissue of hybrid larch (Larix x marschlinsii Coaz) was multiplied on
      Medium M (modified MSG medium supplemented with the plant growth regulators
      (PGRs) 2,4-dichlorophenoxyacetic acid (2,4-D; 9 microM) and N-6-benzyladenine
      (2.25 microM)). After 1 week, cultures were transferred to either MSG lacking
      PGRs (Medium C-) or MSG lacking PGRs but supplemented with 1% activated charcoal
      (Medium C+). Embryos were sampled after 1 week on Medium M, C- or C+. Embryos
      were analyzed by ELISA for abscisic acid (ABA), abscisic acid-glucose ester, 2,4
      D, indole-3-acetic acid (IAA), indole-3-aspartate (IAAsp), zeatin (Z), zeatin
      riboside (ZR), isopentenyladenine (iP) and isopentenyladenosine (iPA). Transfer
      of embryos to Medium C+ reduced the embryo concentrations of 2,4-D and iPA, but
      resulted in elevated concentrations of IAA, IAAsp, ABA, Z, ZR and iP. Charcoal
      reduced 2,4-D concentrations of embryos by an order of magnitude greater than PGR
      free medium alone. Charcoal affected embryo concentrations of five of the eight
      PGRs quantified. Use of either C+ or C- medium as part of the maturation
      protocols also affected germination and plantlet establishment of the embryos. A
      1-week treatment on Medium C+ positively influenced plantlet establishment and
      generally reduced variability during both germination and plantlet establishment.

PMID- 11960769
TI  - Cutting-edge technology. II. Proteomics: core technologies and applications in
      physiology.
AB  - Technologies for proteomics, e.g., studies examining the protein complement of
      the genome, have been in development for over 20 years. More recently, proteomics
      has become formalized by combining techniques for large-scale protein separation
      with very precise, high-fidelity approaches that analyze, identify, and
      characterize the separated proteins. These methods bring to reality the powerful
      scope of proteomics, enabling researchers to investigate cellular function at the
      protein level and thus representing one of proteomics' most fitting applications.
      In this review, we take a brief and concise look at some of the current,
      physiologically relevant technologies that comprise proteomics and report
      specific applications in which proteomics has provided valuable biological
      insight.

PMID- 11960770
TI  - Nuclear receptors. II. Intestinal corticosteroid receptors.
AB  - Two corticosteroid receptors have been cloned; they are the glucocorticoid
      receptor and the mineralocorticoid receptor. These receptors are members of the
      steroid/thyroid/retinoid receptor family of nuclear transactivating factors,
      which are characterized by two highly conserved zinc fingers in the central DNA
      binding domain, a COOH-terminal domain that encompasses the ligand binding site,
      and a variable NH(2)-terminal domain. In addition to these cloned receptors,
      other corticosteroid receptors have recently been identified in intestine.
      Steroid binding studies have identified two novel putative corticosteroid
      receptors in intestinal epithelia, and molecular cloning studies have detected
      two low-affinity receptors in small intestine that are activated by
      corticosteroids and induce CYP3A gene expression. This article focuses on the
      identification of these novel corticosteroid receptors and the potential role
      they may play in intestinal physiology.

PMID- 11960771
TI  - Physiology and pathophysiology of the interstitial cells of Cajal: from bench to
      bedside. IV. Genetic and animal models of GI motility disorders caused by loss of
      interstitial cells of Cajal.
AB  - Several human motility disorders have been shown to be associated with loss or
      defects in interstitial cells of Cajal (ICC) networks. Because tissue samples for
      these studies were taken from patients with well-advanced motility problems, it
      is difficult to determine whether the loss of ICC is a cause or a consequence of
      the disease process. To establish the cause-and-effect relationship of ICC loss
      in motility disorders, it may be feasible to use animal models in which ICC are
      lost as motility dysfunction develops. Several models with defects in ICC
      networks have been developed, and these include animals with defects in the Kit
      signaling pathway (e.g., white-spotting mutants that have defects in Kit
      receptors; steel mutants that have mutations in stem cell factor, the ligand for
      Kit; and animals that are chronically treated with reagents that block Kit or
      downstream signaling proteins). ICC do not die when Kit signaling is blocked,
      rather, they redifferentiate into a smooth muscle-like phenotype. Diabetic
      animals (NOD/LtJ mice), animals with chronic bowel obstruction, and inflammatory
      bowel models also have defects in ICC networks that have been associated with
      motility disorders. By studying these models with molecular and genomic
      techniques it may be possible to determine the signals that cause loss of ICC and
      find ways of restoring ICC to dysfunctional tissues. This article discusses
      recent progress in the utilization of animal models to study the consequences of
      losing ICC on the development of motility disorders.

PMID- 11960772
TI  - Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human
      embryonic kidney cells.
AB  - Cryptdins are antimicrobial peptides secreted by Paneth cells located at the base
      of intestinal crypts. In addition to their antimicrobial function, cryptdins may
      also regulate salt and water secretion by intestinal epithelial cells. Recent
      work with short-circuit current measurements indicated that at least one cryptdin
      peptide, cryptdin 3, induces apical conductance(s) in Cl(-) secretory, including
      cystic fibrosis, epithelia. In the present study, we characterized the cryptdin 3
      induced anion channel activity in human embryonic kidney (HEK) cells with single
      channel patch-clamp techniques. The patch pipette was filled with solution
      containing different concentrations of cryptdin 3, and, after gigaseal formation,
      the channel activity was recorded with either cell-attached or inside-out patch
      modes. We found an anion selective channel with a conductance of 15 pS and open
      probability of 0.19, regardless of cryptdin 3 concentration. The mean open and
      closed times varied with the cryptdin 3 concentration. For cryptdin 3
      concentrations of 10, 4, 1, and 0.5 microg/ml in the pipette, the corresponding
      mean open times were 1.2, 7.0, 9.0, and 17.4 ms and the corresponding mean closed
      times were 1.1, 1.6, 4.2, and 12.5 ms. These results suggest that cryptdin 3
      forms anion-selective channels on the cytoplasmic membrane of HEK cells and that
      the kinetics of one such channel are affected by its interaction with other such
      channels.

PMID- 11960773
TI  - Gastrin biosynthesis in canine G cells.
AB  - Gastrin requires extensive posttranslational processing for full biological
      activity. It is presumed that progastrin is cleaved at pairs of basic amino acids
      by a prohormone convertase to form a glycine-extended intermediate (G-Gly) that
      serves as a substrate for peptidyl-glycine alpha-amidating monooxygenase (PAM),
      resulting in COOH-terminally amidated gastrin. To confirm the nature of
      progastrin processing in a primary cell line, we performed [(35)S]methionine
      labeled pulse-chase biosynthetic experiments in canine antral G cells.
      Radiolabeled progastrin reached a peak earlier than observed for G-Gly or
      amidated gastrin. G-Gly radioactivity accumulated in G cells and preceded the
      appearance of radioactivity in amidated gastrin. The conversion of G-Gly to
      amidated gastrin was enhanced by the PAM cofactor ascorbic acid. To determine
      whether one member of the prohormone convertase family (PC2) was responsible for
      progastrin cleavage, G cells were incubated with PC2 antisense oligonucleotide
      probes. Cells treated with antisense probes had reduced PC2 expression, an
      accumulation of radiolabeled progastrin, and a delay in the formation of amidated
      gastrin. Progastrin in antral G cells is cleaved via PC2 to form G-Gly that is
      converted to amidated gastrin via the actions of PAM.

PMID- 11960775
TI  - A novel ultrasound technique to study the biomechanics of the human esophagus in
      vivo.
AB  - The objectives of this study were to validate a novel ultrasound technique and to
      use it to study the circumferential stress-strain properties of the human
      esophagus in vivo. A manometric catheter equipped with a high-compliance bag and
      a high-frequency intraluminal ultrasonography probe was used to record esophageal
      pressure and images. Validation studies were performed in vitro followed by in
      vivo studies in healthy human subjects. Esophageal distensions were performed
      with either an isovolumic (5-20 ml of water) or with an isobaric (10-60 mmHg)
      technique. Sustained distension was also performed for 3 min in each subject. The
      circumferential wall stress and strain were calculated. In vitro studies indicate
      that the ultrasound technique can make measurements of the esophageal wall with
      an accuracy of 0.01 mm. The in vivo studies provide the necessary data to compute
      the Kirchhoff's stress, Green's strain, and Young's elastic modulus during
      esophageal distensions. The stress-strain relationship revealed a linear shape,
      the slope of which corresponds to the Young's modulus. During sustained
      distensions, we found dynamic changes of stress and strain during the period of
      distension. We describe and validate a novel ultrasound technique that allows
      measurement of biomechanical properties of the esophagus in vivo in humans.

PMID- 11960774
TI  - Intestinal NaCl transport in NHE2 and NHE3 knockout mice.
AB  - Sodium/proton exchangers [Na(+)/H(+) (NHEs)] play an important role in salt and
      water absorption from the intestinal tract. To investigate the contribution of
      the apical membrane NHEs, NHE2 and NHE3, to electroneutral NaCl absorption, we
      measured radioisotopic Na(+) and Cl(-) flux across isolated jejuna from wild-type
      [NHE(+)], NHE2 knockout [NHE2(-)], and NHE3 knockout [NHE3(-)] mice. Under basal
      conditions, NHE(+) and NHE2(-) jejuna had similar rates of net Na(+)
      (approximately 6 microeq/cm(2) x h) and Cl(-) (approximately 3 microeq/cm(2) x h)
      absorption. In contrast, NHE3(-) jejuna had reduced net Na(+) absorption
      (approximately 2 microeq/cm(2) x h) but absorbed Cl(-) at rates similar to NHE(+)
      and NHE2(-) jejuna. Treatment with 100 microM 5-(N-ethyl-N-isopropyl) amiloride
      (EIPA) completely inhibited net Na(+) and Cl(-) absorption in all genotypes.
      Studies of the Na(+) absorptive flux (J) indicated that J in NHE(+) jejunum was
      not sensitive to 1 microM EIPA, whereas J in NHE3(-) jejunum was equally
      sensitive to 1 and 100 microM EIPA. Treatment with forskolin/IBMX to increase
      intracellular cAMP (cAMP(i)) abolished net NaCl absorption and stimulated
      electrogenic Cl(-) secretion in all three genotypes. Quantitative RT-PCR of
      epithelia from NHE2(-) and NHE3(-) jejuna did not reveal differences in mRNA
      expression of NHE3 and NHE2, respectively, when compared with jejunal epithelia
      from NHE(+) siblings. We conclude that 1) NHE3 is the dominant NHE involved in
      small intestinal Na(+) absorption; 2) an amiloride-sensitive Na(+) transporter
      partially compensates for Na(+) absorption in NHE3(-) jejunum; 3) cAMP(i)
      stimulation abolishes net Na(+) absorption in NHE(+), NHE2(-), and NHE3(-)
      jejunum; and 4) electroneutral Cl(-) absorption is not directly dependent on
      either NHE2 or NHE3.

PMID- 11960776
TI  - PKC-zeta is required in EGF protection of microtubules and intestinal barrier
      integrity against oxidant injury.
AB  - Using monolayers of human intestinal (Caco-2) cells, we showed that epidermal
      growth factor (EGF) protects intestinal barrier integrity against oxidant injury
      by protecting the microtubules and that protein kinase C (PKC) is required.
      Because atypical PKC-zeta isoform is abundant in wild-type (WT) Caco-2 cells, we
      hypothesized that PKC-zeta mediates, at least in part, EGF protection. Intestinal
      cells (Caco-2 or HT-29) were transfected to stably over- or underexpress PKC
      zeta. These clones were preincubated with low or high doses of EGF or a PKC
      activator [1-oleoyl-2-acetyl-sn-glycerol (OAG)] before oxidant (0.5 mM H(2)O(2)).
      Relative to WT cells exposed to oxidant, only monolayers of transfected cells
      overexpressing PKC-zeta (2.9-fold) were protected against oxidant injury as
      indicated by increases in polymerized tubulin and decreases in monomeric tubulin,
      enhancement of architectural stability of the microtubule cytoskeleton, and
      increases in monolayer barrier integrity toward control levels (62% less
      leakiness). Overexpression-induced protection was OAG independent and even EGF
      independent, but EGF significantly potentiated PKC-zeta protection. Most
      overexpressed PKC-zeta (92%) resided in membrane and cytoskeletal fractions,
      indicating constitutive activation of PKC-zeta. Stably inhibiting PKC-zeta
      expression (95%) with antisense transfection substantially attenuated EGF
      protection as demonstrated by reduced tubulin assembly and increased microtubule
      disassembly, disruption of the microtubule cytoskeleton, and loss of monolayer
      barrier integrity. We conclude that 1) activation of PKC-zeta is necessary for
      EGF-induced protection, 2) PKC-zeta appears to be an endogenous stabilizer of the
      microtubule cytoskeleton and of intestinal barrier function against oxidative
      injury, and 3) we have identified a novel biological function (protection) among
      the atypical isoforms of PKC.

PMID- 11960777
TI  - Inhibition of gastric cancer cell proliferation by resveratrol: role of nitric
      oxide.
AB  - Resveratrol is a dietary phytochemical that has been shown to inhibit
      proliferation of a number of cell lines, and it behaves as a chemopreventive
      agent in assays that measure the three stages of carcinogenesis. We tested for
      its chemopreventive potential against gastric cancer by determining its
      interaction with signaling mechanisms that contribute to the proliferation of
      transformed cells. Low levels of exogenous reactive oxygen (H(2)O(2)) stimulated
      [(3)H]thymidine uptake in human gastric adenocarcinoma SNU-1 cells, whereas
      resveratrol suppressed both synthesis of DNA and generation of endogenous O(2)(-)
      but stimulated nitric oxide (NO) synthase (NOS) activity. To address the role of
      NO in the antioxidant action of resveratrol, we measured the effect of sodium
      nitroprusside (SNP), an NO donor, on O(2)(-) generation and on [(3)H]thymidine
      incorporation. SNP inhibited DNA synthesis and suppressed ionomycin-stimulated
      O(2)(-) generation in a concentration-dependent manner. Our results revealed that
      the antioxidant action of resveratrol toward gastric adenocarcinoma SNU-1 cells
      may reside in its ability to stimulate NOS to produce low levels of NO, which, in
      turn, exert antioxidant action. Resveratrol-induced inhibition of SNU-1
      proliferation may be partly dependent on NO formation, and we hypothesize that
      resveratrol exerts its antiproliferative action by interfering with the action of
      endogenously produced reactive oxygen. These data are supportive of the action of
      NO against reactive oxygen and suggest that a resveratrol-rich diet may be
      chemopreventive against gastric cancer.

PMID- 11960778
TI  - Regulation of triacylglycerol and phospholipid trafficking by fatty acids in
      newborn swine enterocytes.
AB  - We (Wang H, Berschneider HM, Du J, and Black DD. Am J Physiol Gastrointest Liver
      Physiol 272: G935-G942, 1997; Wang H, Lu S, Du J, Yao Y, Berschneider HM, and
      Black DD. Am J Physiol Gastrointest Liver Physiol 280: G1137-G1144, 2001)
      previously showed that different fatty acids influence synthesis and secretion of
      triacylglycerol (TG) and phospholipid (PL) in a newborn swine enterocyte cell
      line (IPEC-1). The most striking effects were produced by stearic acid (SA;
      18:0), which modestly affected TG and PL synthesis but reduced TG and PL
      secretion, and by eicosapentaenoic acid (EPA; 20:5), which reduced TG and PL
      synthesis and TG secretion relative to oleic acid (OA; 18:1). To define the
      mechanism of these effects, differentiated IPEC-1 cells were incubated for 24 h
      with OA, SA, or EPA and [(3)H]glycerol. Endoplasmic reticulum (ER) and Golgi (G)
      content of labeled lipids and apolipoprotein (apo) B and apoAI protein were
      measured. Relative to OA, SA did not impair ER TG synthesis, but reduced movement
      of labeled TG from ER to G. EPA impaired both ER TG synthesis and movement of
      labeled TG from ER to G. PL followed the same pattern, except ER synthesis of PL
      was relatively unaffected by EPA. Carbonate treatment demonstrated decreased
      partitioning of labeled lipid from ER membrane to lumen in EPA-treated cells.
      Organelle apoB and apoAI content demonstrated opposite patterns after SA and EPA
      incubation. We conclude that SA and EPA adversely influence immature enterocyte
      ER to G lipid trafficking, compared with OA. Furthermore, EPA inhibits ER lipid
      synthesis and transfer of membrane lipid to luminal particles. Regulation of
      apoAI ER to G trafficking is independent of that of apoB.

PMID- 11960779
TI  - Mechanism of staurosporine-induced apoptosis in murine hepatocytes.
AB  - Staurosporine (STS) induces apoptosis in various cell lines. We report in this
      study that primary cultured mouse hepatocytes are less sensitive to STS compared
      with Jurkat cells and Huh-7 cells. In contrast to the cell lines, no apparent
      release of cytochrome c or loss of mitochondrial transmembrane potential was
      detected in primary hepatocytes undergoing STS-induced apoptosis. Caspase-3 was
      activated in primary hepatocytes by STS treatment, but caspase-9 and -12 were not
      activated, and caspase-3 activation is not dependent on caspase-8. These findings
      point to a novel pathway for caspase-3 activation by STS in primary hepatocytes.
      Pretreatment with caspase inhibitor converted STS-induced apoptosis of
      hepatocytes to necrotic cell death without significantly changing total cell
      death. Thus STS causes hepatocytes to commit to death upstream of the activation
      of caspases. We also demonstrated that STS dramatically sensitized primary
      hepatocytes to tumor necrosis factor-alpha-induced apoptosis. STS activated I
      kappa B kinase and nuclear factor-kappa B (NF-kappa B) nuclear translocation and
      DNA binding but inhibited transactivation of I kappa B-alpha, inducible nitric
      oxide synthase, and inhibitor of apoptosis protein-1 in hepatocytes and NF-kappa
      B reporter in transfected Huh-7 cells.

PMID- 11960780
TI  - Alterations of the VIP-stimulated cAMP pathway in rat distal colon after
      abdominal irradiation.
AB  - Ionizing radiation induces hyporesponsiveness of rat colonic mucosa to vasoactive
      intestinal peptide (VIP). Possible mechanisms responsible for this
      hyporesponsiveness of the cAMP communication pathway in rat colon were
      investigated. VIP- and forskolin-stimulated short-circuit current (I(sc))
      responses were studied after a 10-Gy abdominal irradiation in Ussing chambers as
      well as in single, isolated crypts. Adenylyl cyclase (AC) activity and VIP
      receptor characteristics were determined in mucosal membrane preparations. In
      addition, alterations in crypt morphology were studied. Impaired secretory
      responses to VIP and forskolin were observed 4 days after irradiation (decrease
      of 80%). cAMP analog-stimulated I(sc) responses were unchanged. In isolated
      crypts, VIP- and forskolin-stimulated cAMP accumulation was markedly reduced by
      80 and 50%, respectively. VIP-stimulated AC activity and VIP receptor number were
      decreased in membrane preparations. No major change of cellularity was associated
      with these functional alterations. In conclusion, the decreased secretory
      responses to VIP of rat colon are associated with reduced cAMP accumulation,
      decreased AC activity, and diminution of VIP receptor numbers without a marked
      decrease of crypt cell number.

PMID- 11960781
TI  - cAMP modulation of Ca(2+)-regulated exocytosis in ACh-stimulated antral mucous
      cells of guinea pig.
AB  - Effects of cAMP accumulation on ATP-dependent priming and Ca(2+)-dependent fusion
      in Ca(2+)-regulated exocytosis were examined in antral mucous cells of guinea
      pigs by using video-enhanced contrast microscopy. The Ca(2+)-regulated exocytosis
      activated by 1 microM ACh consisted of two phases, an initial transient phase
      followed by a sustained phase, which were potentiated by cAMP accumulation.
      Depletion of ATP by 100 microM dinitrophenol (uncoupler of oxidative
      phosphorylation) or anoxia induced the sustained phase without the initial
      transient phase in Ca(2+)-regulated exocytosis. However, accumulation of cAMP
      before depletion of ATP induced and potentiated an initial transient phase
      followed by a sustained phase in Ca(2+)-regulated exocytosis. This suggests that
      the initial transient phase of Ca(2+)-regulated exocytosis is induced by fusion
      of all primed granules maintained by ATP and that accumulation of cAMP
      accelerates ATP-dependent priming of the exocytotic cycle. Moreover, ACh and
      Ca(2+) dose-response studies showed that accumulation of cAMP shifted the dose
      response curves to the low concentration side, suggesting that it increases
      Ca(2+) sensitivity in the fusion of the exocytotic cycle. In conclusion, cAMP
      accumulation increases the number of primed granules and Ca(2+) sensitivity of
      the fusion, which potentiates Ca(2+)-regulated exocytosis in antral mucous cells.

PMID- 11960782
TI  - Peripheral CRF activates myenteric neurons in the proximal colon through CRF(1)
      receptor in conscious rats.
AB  - Corticotropin-releasing factor (CRF) injected peripherally induces clustered
      spike-burst activity in the proximal colon through CRF(1) receptors in rats. We
      investigated the effect of intraperitoneal CRF on proximal colon ganglionic
      myenteric cell activity in conscious rats using Fos immunohistochemistry on the
      colonic longitudinal muscle/myenteric plexus whole mount preparation. In vehicle
      pretreated rats, there were only a few Fos immunoreactive (IR) cells per ganglion
      (1.2 +/- 0.6). CRF (10 microg/kg ip) induced Fos expression in 19.6 +/- 2.1
      cells/ganglion. The CRF(1)/CRF(2) antagonist astressin (33 microg/kg ip) and the
      selective CRF(1) antagonist CP-154,526 (20 mg/kg sc) prevented intraperitoneal
      CRF-induced Fos expression in the proximal colon (number of Fos-IR
      cells/ganglion: 2.7 +/- 1.2 and 1.0 +/- 1.0, respectively), whereas atropine (1
      mg/kg sc) had no effect. Double labeling of Fos with protein gene product 9.5
      revealed the neuronal identity of activated cells that were encircled by varicose
      fibers immunoreactive to vesicular acetylcholine transporter. Fos
      immunoreactivity was mainly present in choline acetyltransferase-IR nerve cell
      bodies but not in the NADPH-diaphorase-positive cells. These results indicate
      that peripheral CRF activates myenteric cholinergic neurons in the proximal colon
      through CRF(1) receptor.

PMID- 11960783
TI  - EGF promotes gastric mucosal restitution by activating Na(+)/H(+) exchange of
      epithelial cells.
AB  - This study was conducted to determine whether the contributions of epidermal
      growth factor (EGF) to gastric mucosal restitution after injury are mediated by
      stimulation of Na(+)/H(+) exchangers in surface mucous cells (SMC). Intact sheets
      of guinea pig gastric mucosae were incubated in vitro. Intracellular pH (pH(i))
      in SMC was measured fluorometrically, using 2',7'- bis-(2-carboxyethyl)-5-(and-6)
      carboxyfluorescein. Restitution after Triton X-100-induced injury was evaluated
      by recovery of electrical resistance. At neutral luminal pH, exogenous EGF (ex
      EGF) increased pH(i) and enhanced restitution in the absence but not in the
      presence of serosal HCO. During exposure to luminal acid, ex-EGF not only
      prevented intracellular acidosis but also promoted restitution. These effects of
      ex-EGF were blocked by serosal amiloride or anti-EGF-receptor antibody. In the
      absence of ex-EGF, restitution was inhibited by replacement of luminal and
      serosal solutions with fresh solutions and was blocked more completely by serosal
      anti-EGF-receptor antibody. These results suggest that both endogenous and ex-EGF
      contribute to restitution via basolateral EGF receptors, with effects mediated,
      at least in part, by stimulation of basolateral Na(+)/H(+) exchangers.

PMID- 11960784
TI  - 5-HT(2A) receptors: location and functional analysis in intestines of wild-type
      and 5-HT(2A) knockout mice.
AB  - The distribution and function of the 5-hydroxytryptamine (5-HT(2A)) receptor were
      investigated in the intestines of wild-type (5-HT(2A) +/+) and knockout (5-HT(2A)
      -/-) mice. In 5-HT(2A) +/+ mice, rats, and guinea pigs, 5-HT(2A) receptor
      immunoreactivity was found on circular and longitudinal smooth muscle cells,
      neurons, enterocytes, and Paneth cells. Muscular 5-HT(2A) receptors were
      concentrated in caveolae; neuronal 5-HT(2A) receptors were found intracellularly
      and on the plasma membranes of nerve cell bodies and axons. Neuronal 5-HT(2A)
      immunoreactivity was detected as early as E14 in ganglia, intravillus nerves, and
      the deep muscle plexus. The 5-HT(2A) -/- colon did not express 5-HT(2A) receptors
      and did not contract in response to exogenous 5-HT. 5-HT(2A) -/- enterocytes were
      smaller, Paneth cells fewer, and muscle layers thinner (and showed degeneration)
      compared with those of 5-HT(2A) +/+ littermates. The 5-HT(2A) receptor may thus
      be required for the maintenance and/or development of enteric neuroeffectors and
      other enteric functions, although gastrointestinal and colonic transit times in 5
      HT(2A) -/- and +/+ mice did not differ significantly.

PMID- 11960785
TI  - HSP27 phosphorylation and interaction with actin-myosin in smooth muscle
      contraction.
AB  - We have investigated the role of heat shock protein 27 (HSP27) phosphorylation
      and the association of HSP27 with contractile proteins actin, myosin, and
      tropomyosin. Smooth muscle cells were labeled with [(32)P]orthophosphate. C2
      ceramide (0.1 microM), an activator of protein kinase C (PKC), induced a
      sustained increase in HSP27 phosphorylation that was inhibited by calphostin C.
      C2-ceramide-induced (0.1 microM) sustained colonic smooth muscle cell contraction
      was accompanied by significant increases in the association of HSP27 with
      tropomyosin and in the association of HSP27 with actin. The significant increases
      occurred at 30 s after stimulation and were sustained at 4 min. Contraction was
      also associated with strong colocalization of HSP27 with tropomyosin and with
      actin as observed after immunofluorescent labeling of tropomyosin, actin, and
      HSP27 followed by confocal microscopy. Transfection of smooth muscle cells with
      HSP27 phosphorylation mutants indicated that phosphorylation of HSP27 could
      affect myosin association with actin. In conclusion 1) HSP27 phosphorylation
      appears to be necessary for reorganization of HSP27 inside the cell and seems to
      be directly correlated with the PKC signal transduction pathway, and 2) agonist
      induced phosphorylation of HSP27 modulates actin-myosin interaction through thin
      filament regulation of tropomyosin.

PMID- 11960788
TI  - A personal introduction to eye movements.
AB  - The presentations at this meeting demonstrate that the control of eye movements
      is probably the best understood motor system from the level of genes and
      molecules to the neural orchestration of complex behaviors. Here I review my
      early involvement in this field, with personal impressions of how our current
      concepts developed and the individuals who shaped them.

PMID- 11960786
TI  - Electrical rhythmicity and spread of action potentials in longitudinal muscle of
      guinea pig distal colon.
AB  - Using simultaneous intracellular recordings, we have characterized 1) electrical
      activity in the longitudinal muscle (LM) of isolated segments of guinea pig
      distal colon free to contract spontaneously and 2) extent of propagation of
      spontaneous action potentials around the circumference of the colon. In all
      animals, rhythmical spontaneous depolarizations (SDs) were recorded that are
      usually associated with the generation of action potentials. Recordings from
      pairs of LM cells, separated by 100 microm in the circumferential axis, revealed
      that each action potential was phase locked at the two electrodes (mean
      propagation velocity: 3 mm/s). However, at an increased electrode separation
      distance of 1 mm circumferentially, action potentials and SDs became increasingly
      uncoordinated at the two recording sites. No SDs or action potentials ever
      propagated from one circumferential edge to the other (i.e., 13 mm apart). When
      LM strips were separated from the myenteric plexus and circular muscle,
      rhythmically firing SDs and action potentials were still recorded. Atropine (1
      microM) or tetrodotoxin (1 microM) either reduced the frequency of SDs or
      temporarily abolished activity, whereas nifedipine (1 microM) always abolished
      SDs and action potentials. Kit-positive interstitial cells of Cajal were present
      at the level of the myenteric plexus and circular and longitudinal muscle. In
      summary, SDs and action potentials in LM propagate over discrete localized zones,
      usually <1 mm around the circumference of the colon. Furthermore, in contrast to
      the classic slow wave, rhythmic depolarizations in LM appear to be generated by
      an intrinsic property of the smooth muscle itself and are critically dependent on
      opening of L-type Ca(2+) channels.

PMID- 11960789
TI  - Extraocular muscle: cellular adaptations for a diverse functional repertoire.
AB  - Oculomotor control systems are considerably more complex and diverse than are
      spinal skeletomotor systems. Moreover, individual skeletal muscles are frequently
      functional role-specific, while all extraocular muscles operate across a very
      wide dynamic range. We contend that the novel phenotype of the extraocular
      muscles is a direct consequence of the functional demands imposed upon this
      muscle group by the central eye movement controllers. This review highlights five
      basic themes of extraocular muscle biology that set them apart from more typical
      skeletal muscles, specifically, the (a) novel innervation pattern, (b)
      heterogeneity in contractile proteins, (c) structural and functional
      compartmentalization of the rectus and oblique muscles, (d) diversity of
      extraocular muscle fiber types, and (e) relationship between the novel muscle
      phenotype and the differential response of these muscles in neuromuscular and
      endocrine disease. Finally, new data from broad genome-wide profiling studies are
      reviewed, with global gene expression patterns lending substantial support to the
      notion that the extraocular muscles are fundamentally different from traditional
      skeletal muscle. This novel eye muscle phenotype represents an adaptation that
      exploits the full range of variability in skeletal muscle to meet the needs of
      visuomotor systems.

PMID- 11960790
TI  - The orbital pulley system: a revolution in concepts of orbital anatomy.
AB  - Magnetic resonance imaging (MRI) now enables precise visualization of the
      mechanical state of the living human orbit. Resulting insights have motivated
      histological re-examination of human and simian orbits, providing abundant
      consistent evidence for the active pulley hypothesis, a re-formulation of ocular
      motor physiology. Each extraocular muscle (EOM) consists of a global layer (GL)
      contiguous with the tendon and inserting on the eyeball, and a similar-sized
      orbital layer (OL) inserting on a connective tissue ring forming the EOM pulley.
      The pulley controls the EOM path and serves as the EOM's functional origin.
      Activity of the OL positions the pulley along each rectus EOM to assure that its
      pulling direction shifts by half the change in ocular orientation, the half-angle
      behavior characteristic of a linear ocular motor plant. Half-angle behavior is
      equivalent to Listing's law of ocular torsion, and makes 3-D ocular rotations
      effectively commutative. Pulleys are configured to maintain oblique EOM paths
      orthogonal to half-angle behavior, and violate Listing's law during the vestibulo
      ocular reflex. Rectus pulley positions shift during convergence, facilitating
      stereopsis. Innervations, fiber types, and metabolism of the OL and GL differ,
      consistent with the elastic loading of the former, and viscous loading of the
      latter. Disorders of the location and stability of rectus pulleys are associated
      with predictable patterns of incomitant strabismus that may mimic cranial nerve
      palsies. Surgical interventions improve defective pulley function. Understanding
      of ocular motor control requires characterization of the behavior of the EOM
      pulleys as well as knowledge of angular eye orientation.

PMID- 11960791
TI  - Mechanics of eye movements: implications of the "orbital revolution".
AB  - Our understanding of the functional structure of extraocular muscles has
      undergone a profound change: while these muscles used to be represented by
      strings running straight from their origin in the posterior orbita to their
      insertion on the globe, we now know that their paths and pulling directions are
      dominated by fibromuscular pulley structures, keeping them close to the orbital
      wall for most of their path. An overview is presented of recent models that have
      been developed to understand the implications of muscle pulleys for the neural
      control of eye movements and the applications of such models to the
      interpretation of experimental data.

PMID- 11960792
TI  - Differential susceptibility of the ocular motor system to disease.
AB  - This review summarizes an alternative approach to the understanding of
      neuromuscular disease. By contrasting disease susceptibility of extraocular
      muscle and ocular motor neurons, it is hoped that unique insights into disease
      mechanisms may be identified. Disorder of eye movements leads to dramatic
      symptoms for patients and the ocular motor system is relatively limited in its
      ability to compensate rapidly for such disruptions. However, more profound
      reasons exist as to why myasthenia gravis compromises neuromuscular transmission
      at ocular muscle synapses as well as why Graves' ophthalmopathy exists. In
      contrast, muscular dystrophies spare the eye muscles while devastating all other
      skeletal muscles; the same is true for motor neuron diseases. It is hoped that
      this review will encourage others to view the world of neuromuscular diseases as
      delineated into those that spare the ocular motor system and those that do not.

PMID- 11960793
TI  - Applications of molecular genetics to the understanding of congenital ocular
      motility disorders.
AB  - The congenital fibrosis syndromes (CFS), including congenital fibrosis of the
      extraocular muscles (CFEOM) and Duane syndrome (DS), are rare congenital
      strabismus syndromes that present with nonprogressive restrictive ophthalmoplegia
      with or without ptosis. Although historically believed to result from primary
      extraocular muscle (EOM) fibrosis, our laboratory's work is based on the
      hypothesis that these disorders result from distinct, but analogous,
      developmental defects of the oculomotor (nIII), trochlear (nIV), and abducens
      (nVI) nuclei. We have defined three inherited CFEOM phenotypes (CFEOM1-3) and
      have mapped each phenotype to a distinct genetic locus (FEOM1-3). Individuals
      with CFEOM1 are born with bilateral ptosis and both eyes fixed in a downward
      position with absent upgaze and aberrant horizontal gaze. This disorder maps to
      the FEOM1 locus on chromosome 12cen.(1,2) Neuropathology studies of CFEOM1 reveal
      the absence of the superior division of oculomotor nerve and its corresponding
      alpha motor neurons in the midbrain, with abnormalities of target EOMs.(3) These
      neuropathology findings parallel those previously identified in Duane syndrome,
      in which there is an absence of nVI and the abducens nerve.(4,5) Individuals with
      CFEOM2 are born with bilateral ptosis and exotropia. This atypical form of CFEOM
      maps to the FEOM2 locus on chromosome 11q13 and results from mutations in ARIX
      (PHOX2A).(6,7) ARIX encodes a homeodomain transcription factor protein previously
      shown to be required for nIII/nIV development in mouse and zebrafish.(8,9)
      Together, these findings support the hypothesis that the congenital fibrosis
      syndromes result from parallel defects in nIII, nIV, and nVI nuclear development.
      Functional studies of the CFEOM genes should provide additional insight into the
      unique features of the extraocular lower motor neuron axis in health and disease.
      (For full (refs. 1-9), see reference list of the main paper.)

PMID- 11960794
TI  - Calcium channelopathy mutants and their role in ocular motor research.
AB  - Thanks to technical advances in eye movement recording, the mouse is destined to
      become increasingly important in ocular motor research. An advantage of this
      species is the wide range of existing mutant strains and techniques to generate
      new mutations affecting specific cell types. Mutations of ion channels may be
      used to modulate the intrinsic properties of neurons, and this approach may
      generate insight into the degree to which neuronal computations depend upon those
      intrinsic properties as opposed to the properties of circuits of neurons.
      Dendritic calcium currents carried by P-type voltage-activated calcium channels
      have been widely postulated to perform important computational functions in
      cerebellar Purkinje cells. Mutations of this channel lead to human diseases, and
      several ataxic strains of mice are now known to harbor mutations of this calcium
      channel. Murine P-channel mutants such as rocker are ataxic, but have normal or
      near-normal numbers of cerebellar Purkinje cells and thus offer the opportunity
      to study the effects of biophysical perturbations as opposed to outright cell
      destruction or inactivation. Initial studies of rocker mice reveal an array of
      ocular motor abnormalities, including static hyperdeviation of the eyes and an
      attenuation of vestibulo-ocular reflex gains at high stimulus frequencies. The
      pattern of gain and phase abnormalities is entirely different in lurcher, an
      ataxic mutant in which Purkinje cells degenerate. The ocular motor abnormalities
      of rocker progress with animal age, underscoring the importance of careful
      attention to animal age when performing ocular motor studies in this short-lived
      species.

PMID- 11960795
TI  - Modern concepts of brainstem anatomy: from extraocular motoneurons to
      proprioceptive pathways.
AB  - The extraocular muscles, unlike the skeletal muscles, contain non-twitch muscle
      fibers. Recent experiments have located the non-twitch motoneurons. They lie
      around the periphery of the oculomotor, trochlear and abducens nuclei, separate
      from the more usual twitch motoneurons that cluster within the boundaries of the
      classical motor nuclei. The premotor inputs to non-twitch neurons were traced by
      the injection of rabies virus into the distal tip of the lateral rectus muscle.
      Retrogradely labeled cells were found in areas associated with the neural
      integrator, vergence and smooth pursuit premotor areas, but not the saccadic
      premotor burst neurons or the direct vestibulo-ocular pathways. The rabies
      tracing emphasizes for the first time that the central mesencephalic reticular
      formation (cMRF) and the supraoculomotor area exert direct premotor control over
      the non-twitch motoneurons. Because the two sets of motoneurons do not receive
      the same afferents, they must have different functions; these are not yet
      clarified. These results are not compatible with the concept of a single final
      common pathway from motoneurons to eye muscles. Putative sensory receptors,
      palisade endings, are located at the tips of non-twitch muscle fibers reminiscent
      of an inverted muscle spindle, which would make the non-twitch motoneurons, gamma
      motoneurons. We propose that twitch motoneurons are the major source of tension
      used for eye movements, whereas non-twitch motoneurons are more important for
      fine alignment of the eyes. Furthermore, the non-twitch motoneurons could be
      controlled through sensory feedback networks (including perhaps proprioceptive
      signals from the palisade endings) that are relayed through the superior
      colliculus and via cMRF to the non-twitch motoneurons. The clinical repercussions
      of these hypotheses are discussed.

PMID- 11960796
TI  - Studies of the role of the paramedian pontine reticular formation in the control
      of head-restrained and head-unrestrained gaze shifts.
AB  - Results of three experiments related to the role of the paramedian pontine
      reticular formation (PPRF) in the control of gaze are described. (1) Chronic unit
      recording methods, used to study the on-directions of short-lead burst neurons in
      head-restrained monkeys, and (2) reversible inactivation techniques confirmed the
      traditional view of the importance of PPRF in the control of horizontal eye
      movements. Reversible inactivation of neurons in the vicinity of identified short
      lead burst neurons produced dramatic reductions in the speed of saccades to
      horizontal target displacements. The reductions in velocity were largely
      compensated for by an increase in saccade duration. Only minor, if any, effects
      were observed upon the velocity, duration, and amplitude of saccades to upward
      target displacements. (3) Microstimulation was applied to omnipause neurons to
      gate activity of excitatory burst neurons that discharge during coordinated eye
      head movements. The microstimulation failed to noticeably slow (prevent) head
      movements when stimulation was applied during (prior to onset of) gaze shifts,
      suggesting that signals relayed to motoneurons innervating the neck muscles are
      not inhibited by the omnipause neurons. In other words, the desired gaze signal
      is parsed into eye and head pathways upstream of the excitatory burst neurons.

PMID- 11960798
TI  - Contribution of the superior colliculus and the mesencephalic reticular formation
      to gaze control.
AB  - Converging lines of evidence support a role for the intermediate and deep layers
      of the superior colliculus (SC) and the mesencephalic reticular formation (MRF)
      in the control of combined head and eye movements (i.e., gaze). Recent
      microstimulation, single-cell recording, and lesion experiments are reviewed in
      which monkeys are free to move their heads. Cells in the SC discharge in advance
      of combined head and eye movements and most likely provide a gaze error signal to
      downstream structures. In contrast, the neurons in the MRF are of at least two
      types. Eye cells have features that are similar to neurons in the rostral portion
      of the SC, but fire before the onset of horizontal eye movments. A second group
      of MRF neurons begin to fire after the onset of the gaze shift and are most
      closely associated with movements of the head. The peak discharge of these late
      onset MRF neurons occurs near the peak head velocity. Stimulation in the rostral
      SC generates eye movements with fixed amplitude and direction. A similar response
      is noted after stimulation of the more dorsal portion of the caudal MRF.
      Stimulation in the caudal portion of the SC produces combined head and eye
      movements of fixed amplitude. Electrical activation of the more ventral portions
      of the caudal MRF generates goal-directed and centering eye movements. Temporary
      inactivation of the SC with the GABA agonist muscimol generated hypometria and
      curved trajectories of contralateral eye movements. Inactivation of the caudal
      MRF produced contralateral hypermetria and ipsilateral hypometria of saccades.
      Release of the monkey's head demonstrated a profound contralateral head tilt.
      Taken together, these data suggest that the gaze signal generated in the SC is
      filtered by neurons in the MRF to generate a feedback signal of eye motor error.
      The head signal found in the MRF could cancel a portion of the gaze signal coming
      from the SC in the form of head velocity feedback.

PMID- 11960797
TI  - The contribution of midbrain circuits in the control of gaze.
AB  - The midbrain contains several structures important for the generation of
      torsional and vertical eye movements including the rostral interstitial nucleus
      of the MLF (riMLF) and the interstitial nucleus of Cajal (iC). While the riMLF is
      the immediate premotor structure for the generation of torsional and vertical
      saccades, the iC is considered a major part of the neural integrator for
      torsional and vertical eye movements. Experiments in monkeys show that a
      unilateral inactivation of the riMLF with muscimol leads to spontaneous
      contralesional torsional nystagmus, whereas an iC inactivation causes
      ipsilesional torsional nystagmus. In addition, inactivation of either structure
      leads to a tonic ocular torsion to the contralesional side. While the deficits
      after a riMLF lesion are thought to result from an imbalance of the saccade
      generator, a vestibular imbalance probably causes the deficits after an iC
      lesion. Contralesional and ipsilesional torsional nystagmus is also found in
      patients with unilateral mesencephalic lesions. A detailed analysis of the
      lesions from MRI scans shows a preferential involvement of the riMLF for patients
      with contralesional torsional nystagmus, and a major involvement of iC in cases
      with ipsilesional torsional nystagmus. Thus, the direction of torsional nystagmus
      appears to be a valuable topodiagnostic sign for patients with midbrain lesions.

PMID- 11960799
TI  - Neural discharge in the superior colliculus during target search paradigms.
AB  - Neural studies of oculomotor function in the past have been conducted with the
      use of very simple visual stimuli. More recently there has been a new emphasis on
      using more natural stimuli to extend our knowledge of oculomotor organization.
      Visual search paradigms are an example of the use of these more natural visual
      surrounds. In search a subject must locate and saccade to a target that appears
      simultaneously with an array of distractors. When monkeys are used in this
      paradigm, it is possible to record from neurons located in various central
      structures in the brain while the initial visual response, subsequent
      discrimination processes and final saccadic movement unfold. In the present study
      we used an array of four visual stimuli, and the target was distinguished by its
      odd color from three distractors of uniform color. Location of the target within
      the array and its color were randomly selected on each trial. Neurons located in
      the deeper layers of the superior colliculus (SC) were recorded by standard
      methods in blocks of search trials. We found several new features in the
      discharge of SC neurons using this search paradigm that have not previously been
      reported in studies using single-target visual displays. (1) In contrast to the
      "winner take all" behavior previously reported for the SC, we found evidence of
      concurrent processing of alternative movement vectors. When incorrect movements
      were made to distractor locations, this concurrent activity was associated with
      significantly shorter intersaccadic intervals. (2) The discharge profile of the
      visual response in many units was modified by the appearance of a second
      prominent peak which followed the initial phasic visual response, but which was
      clearly differentiated from a third burst in activity associated with a saccade
      into the cell's response field. In some neurons, the activity in this second peak
      was discriminatory for the impending saccade vector. That is, it was larger when
      the target appeared in the response field of the cell than when it contained a
      distractor. This target selection signal was thus distinct from the burst
      normally associated with saccades into the movement fields of SC neurons. (3)
      Some saccades in search had a curved trajectory bowing toward the location of a
      distractor. These saccades were accompanied by an elevated discharge of neurons
      coding that distractor.

PMID- 11960800
TI  - Midbrain disorders of vertical gaze: a quantitative re-evaluation.
AB  - The mesodiencephalic junction is the site of the prenuclear control of vertical
      eye motion. We measured vertical saccades, smooth pursuit (SP), the vertical
      vestibulo-ocular reflex (VOR), and its interactions with vision during active
      head motion in 21 patients with midbrain lesions causing palsy of vertical
      saccades, upward, downward, or in both directions. Most patients with limited
      slow or slowed saccades in one direction on clinical examination had slowed
      saccades in the opposed direction. SP gain was decreased in both directions in
      most patients, and decreased upward or downward in few. VOR gain was subnormal in
      both directions in many patients, and upward only in one; phase lead of the VOR
      was recorded in 33% of them. Subnormal SP and VOR gains were often dissociated.
      Visually enhanced VOR gains were subnormal in both directions in many patients.
      Cancellation of the VOR was impaired in many patients, both upward and downward
      in most and upward in few patients. Gaze (eye plus head) tracking gain was
      subnormal in 29% of patients. Defective SP and defective cancellation of the VOR
      during head free tracking were often dissociated. We conclude that VOR and SP
      gains are usually subnormal in patients with paresis of vertical saccades.
      Impairment of pursuit and the VOR are often dissociated. Phase lead of the VOR
      implicates damage to velocity-to-position neural integrator for vertical eye
      motion. These associations and dissociations of impaired vertical eye motion
      signify discrete structural and functional effects of supranuclear midbrain
      damage that are undetected by examination of saccades.

PMID- 11960801
TI  - Cerebellar influences on saccade plasticity.
AB  - Inaccurate saccades adapt to become more accurate. In this experiment the role of
      cerebellar output to the oculomotor system in adapting saccade size was
      investigated. We measured saccade adaptation after temporary inactivation of
      saccade-related neurons in the caudal part of the fastigial nucleus which
      projects to the oculomotor brain stem. We located caudal fastigial nucleus
      neurons with single unit recording and injected 0.1% muscimol among them. Two
      monkeys received bilateral injections and two monkeys unilateral injections.
      Unilateral injections made ipsiversive saccades hypermetric (gains >1.5) and
      contraversive saccades hypometric (gains approximately 0.6). Bilateral injections
      made both leftward and rightward saccades hypermetric (gains >1.5). During
      unilateral inactivation neither ipsiversive nor contraversive saccade size
      adapted after approximately 1,000 saccades. During bilateral inactivation,
      adaptation was either small or very slow. Most intact monkeys completely adapt
      after approximately 1,000 saccades to similar dysmetrias produced by
      intrasaccadic target displacement. After the monkeys receiving bilateral
      injections made >1,000 saccades in each horizontal direction, we placed them in
      the dark so that the muscimol dissipated without the monkeys receiving visual
      feedback about its saccade gain. After the dark period, 20-degree saccades were
      adapted to be 12% smaller, and 4-degree saccades to be 7% smaller. We expect this
      difference in adaptation because during caudal fastigial nucleus inactivation,
      monkeys made many large overshooting saccades and few small overshooting
      saccades. We conclude from these results that: (1) caudal fastigial nucleus
      activity is important in adapting dysmetric saccades; and (2) bilateral caudal
      fastigial nucleus inactivation impairs the relay of adapted signals to the
      oculomotor system, but it does not stop all adaptation from occurring.

PMID- 11960802
TI  - Distributed model of collicular and cerebellar function during saccades.
AB  - How does the brain tell the eye where to go? Classical models of rapid eye
      movements are lumped control systems that compute analogs of physical signals
      such as desired eye displacement, instantaneous error, and motor drive.
      Components of these lumped models do not correspond well with anatomical and
      physiological data. We have developed a more brain-like, distributed model
      (called a neuromimetic model), in which the superior colliculus (SC) and
      cerebellum (CB) play novel roles, using information about the desired target and
      the movement context to generate saccades. It suggests that the SC is neither
      sensory nor motor; rather it encodes the desired sensory consequence of the
      saccade in retinotopic coordinates. It also suggests a non-computational scheme
      for motor control by the cerebellum, based on context learning and a novel
      spatial mechanism, the pilot map. The CB learns to use contextual information to
      initialize the pilot signal that will guide the saccade to its goal. The CB
      monitors feedback information to steer and stop the saccade, and thus replaces
      the classical notion of a displacement integrator. One consequence of this model
      is that no desired eye movement signal is encoded explicitly in the brain; rather
      it is distributed across activity in both the SC and CB. Another is that the
      transformation from spatially coded sensory information to temporally coded motor
      information is implicit in the velocity feedback loop around the CB. No explicit
      spatial-to-temporal transformation with a normalization step is needed.

PMID- 11960803
TI  - The cerebellar contribution to eye movements based upon lesions: binocular three
      axis control and the translational vestibulo-ocular reflex.
AB  - The study of human cerebellar patients and monkeys with experimental cerebellar
      lesions has taught us much about the role of the cerebellum in normal ocular
      motor control. Here we emphasize recent findings that point to a role for the
      cerebellum in (1) the control of the three-dimensional axis about which the eye
      rotates in response to visual and vestibular stimuli, and (2) the generation of
      the translational VOR. Findings in cerebellar patients include abnormalities of
      eye torsion during attempted fixation that suggest a cerebellar role in the
      control of torsion so that Listing's law is obeyed. Abnormal torsion during
      vertical pursuit suggests that central processing of information for smooth
      pursuit may be based upon a phylogenetically old, semicircular canal coordinate
      scheme. Inappropriate and disconjugate vertical and torsional eye movements
      ("cross-coupling") occur during brief, high-acceleration rotations of the head.
      This suggests a role for the cerebellum in the binocular control of the rotation
      axis of the VOR. Finally, abnormalities of the modulation of the translational
      VOR with near viewing in cerebellar patients, but with sparing of the very
      initial 25-30 msec of response, suggests an important role for the cerebellum in
      the translational VOR.

PMID- 11960804
TI  - Spatial orientation of caloric nystagmus.
AB  - The spatial orientation of the slow-phase eye velocity of caloric nystagmus was
      investigated in cynomolgus monkeys after all six semicircular canals had been
      plugged. Normal animals generate responses that have dominant convective
      components produced by movement of the endolymph in the lateral canal toward or
      away from gravity. As a result, the direction of horizontal slow-phase velocity
      induced by cold-water irrigation changes direction with changes in head position
      with regard to gravity. Plugging produced a dense overgrowth of bone that blocked
      the flow of endolymph, but the end organs were intact. Robust caloric nystagmus
      was elicited after recovery, but the horizontal (yaw) component was now always
      toward the stimulated (ipsilateral) side, regardless of head position re gravity.
      The induced caloric nystagmus had strong spatial orientation properties after
      canal plugging. With animals upright, the three-dimensional velocity vector of
      the caloric nystagmus was close to the yaw axis with small vertical and roll
      components. Roll components became stronger in supine and prone positions and
      vertical components were enhanced in the right- and left-side down positions. In
      each instance, the addition of the roll and vertical components moved the
      velocity vector of the nystagmus closer to the spatial vertical. Modeling
      supported the postulate that the caloric nystagmus after canal plugging is
      influenced by three factors: (1) a reduction in neural activity in the ampullary
      nerves on the stimulated side due to cooling of the nerves; (2) contraction of
      the endolymph in the closed space between the cupula and the plug due to cooling,
      which resulted in deflection of the cupula and hair cells toward the plug
      (ampullofugal deflection); and (3) alignment of eye velocity to gravity due to
      the orientation properties of velocity storage. Although convection is the most
      prominent factor in producing caloric responses in the normal state, our results
      suggest that alteration of nerve activity due to thermal effects, endolymph
      contraction or expansion, and velocity storage are also likely to contribute to
      the total response.

PMID- 11960805
TI  - The role of the lateral intraparietal area of the monkey in the generation of
      saccades and visuospatial attention.
AB  - The brain cannot monitor or react towards the entire world at a given time.
      Instead, using the process of attention, it selects objects in the world for
      further analysis. Neuronal activity in the monkey intraparietal area has the
      properties appropriate for a neuronal substrate of attention: instead of all
      objects being represented in the parietal cortex, only salient objects are. Such
      objects can be salient because of their physical properties (recently flashed
      objects or moving objects) or because they can be made important to the animal by
      virtue of a task. Although lateral intraparietal area (LIP) neurons respond
      through the delay period of a memory-guided saccade, they also respond in an
      enhanced manner to distractors flashed during the delay period of a memory-guided
      saccade being generated to a position outside the receptive field. This activity
      parallels the monkey's psychophysical attentional process: attention is
      ordinarily pinned at the goal of a memory-guided saccade, but it shifts briefly
      to the locus of a task-irrelevant distractor flashed briefly during the delay
      period and then returns to the goal. Although neurons in LIP have been implicated
      as being directly involved in the generation of saccadic eye movements, their
      activity does not predict where, when, or if a saccade will occur. The ensemble
      of activity in LIP, however, does accurately describe the locus of attention.

PMID- 11960806
TI  - Effects of cortical lesions on saccadic: eye movements in humans.
AB  - Our knowledge of the cortical control of saccadic eye movements (saccades) in
      humans has recently progressed mainly because of lesion and transcranial magnetic
      stimulation (TMS) studies, but also because of functional imaging. It is now well
      known that the frontal eye field is involved in the control of intentional
      saccades, the parietal eye field in that of reflexive saccades, the supplementary
      eye field (SEF) in the initiation of motor programs comprising saccades, the pre
      SEF in the learning of these programs, and the dorsolateral prefrontal cortex
      (DLPFC) in saccade inhibition, prediction and spatial working memory. Saccades
      may also be used as a convenient model of motricity to study general cognitive
      processes such as motivation and spatial memory. Thus, it has been shown that the
      posterior part of the anterior cingulate cortex, called the cingulate eye field,
      is involved in motivation and the preparation of all intentional saccades, but
      not in reflexive saccades. Recently, our understanding of the cortical control of
      spatial memory has noticeably progressed by using the simple visuo-oculomotor
      model represented by the memory-guide saccade paradigm, in which a single saccade
      is made to the remembered position of a unique visual item presented a while
      before. Transcranial magnetic stimulation studies have determined that after a
      brief stage of spatial integration in the posterior parietal cortex (inferior to
      300 ms), short-term spatial memory (i.e., up to 15-20 seconds) is controlled by
      the DLPFC. Behavioral and lesion studies have shown that medium-term spatial
      memory (between 15 and 20 seconds and a few minutes) is specifically controlled
      by the parahippocampal cortex, before long-term memorization (i.e., after a few
      minutes) in the hippocampal formation. These different but complementary study
      methods used in humans have thus contributed to a better understanding of both
      eye movement physiology and general cognitive processes preparing motricity as
      whole.

PMID- 11960807
TI  - Visual-vestibular and visuovisual cortical interaction: new insights from fMRI
      and pet.
AB  - PET and fMRI studies have revealed that excitation of the vestibular system by
      caloric or galvanic stimulation not only activates the parietoinsular vestibular
      cortex but also bilaterally deactivates the occipital visual cortex. Likewise,
      visual motion stimulation not only activates the visual cortex but also
      deactivates the parietoinsular vestibular cortex. These findings are functionally
      consistent with the hypothesis of an inhibitory reciprocal visual-vestibular
      interaction for spatial orientation and motion perception. Transcallosal
      visuovisual interaction between the two hemispheres was found by using half-field
      visual motion stimulation: activation of motion-sensitive areas hMT/V5 and
      deactivations of the primary visual cortex contralateral to the stimulated
      hemisphere. The functional significance of these inter- and intra-sensory
      interactions could be that they (A) allow a shift of the sensorial weight between
      two incongruent sensory inputs and (B) ensure a correspondence of the two
      hemispheres during evaluation of contradictory motion stimulation of the right
      and left hemifields. In terms of mathematical modeling, these findings may
      reflect the concepts of a sensory conflict mechanism or a mismatch between
      expected and actual sensory input.

PMID- 11960808
TI  - Scanpaths: the path to understanding abnormal cognitive processing in
      neurological disease.
AB  - Scanpaths, the sequence of saccades and fixations during visual search, provide
      the means to study a range of cognitive activities: planning, visuospatial
      attention, and spatial working memory. By measuring scanpaths, we have been able
      to identify impairment of working memory in patients with spatial hemineglect.
      Scanpaths during cognitively demanding tasks indicate a defect of working memory
      in patients with Parkinson's disease. Studies of scanpaths in patients with
      homonymous hemianopia have provided the means to develop a new strategy for
      visual rehabilitation.

PMID- 11960809
TI  - Antisaccades and task switching: studies of control processes in saccadic
      function in normal subjects and schizophrenic patients.
AB  - Executive functions allow us to respond flexibly rather than stereotypically to
      the environment. We examined two such functions, task switching and inhibition in
      the antisaccade paradigm, in two studies. One study involved 18 normal subjects;
      the other, 21 schizophrenic patients and 16 age-matched controls. Subjects
      performed blocks of randomly mixed prosaccades and antisaccades. Repeated trials
      were preceded by the same type of trial (i.e., an antisaccade following an
      antisaccade), and switched trials were preceded by a trial of the opposite type.
      We measured accuracy rate and latency as indices of processing costs. Whereas
      schizophrenic patients had a threefold increase in error rate for antisaccades
      compared to normals, the effect of task switching on their accuracy did not
      differ from that in normal subjects. Moreover, the accuracy rate of trials
      combining antisaccade and task switching was equivalent to a multiplication of
      the accuracy rates from trials in which each was done alone. Schizophrenic
      latencies were disproportionately increased for antisaccades, but again they were
      no different from normal subjects in the effect of task switching. In both groups
      the effect of task switching on antisaccades was a paradoxical latency reduction.
      We conclude that the executive dysfunction in schizophrenia is not generalized
      but selective, sparing task switching from exogenous cues, in which the switch is
      limited to a stimulus-response remapping. The accuracy data in both groups
      support independence of antisaccade and task-switching functions. The paradoxical
      task-switching benefit in antisaccadic latency effects challenges current models
      of task switching. It suggests either carryover inhibition by antisaccadic
      performance in the prior trial or facilitation of antisaccades by simultaneous
      performance of other cognitive operations.

PMID- 11960810
TI  - Neural mechanisms for the control of vergence eye movements.
AB  - Our recent studies in non-human primates have identified and characterized
      cerebro-ponto-cerebellar pathways involved in the control of vergence eye
      movements. Specifically, within the deep cerebellar nuclei and nucleus
      reticularis tegmenti pontis, we have identified neurons that are related to
      either the near response (convergence and increased ocular accommodation) or the
      far response (divergence and decreased ocular accommodation). In addition, within
      the prearcuate region (area 8a), we have characterized neurons related not only
      to either the far response or the near response, but also to the sensorimotor
      transformations underlying these eye movements. Because the vergence-related
      prearcuate region abuts the frontal eye fields, we suggest that the extent of the
      frontal eye fields be expanded to include this region. We further suggest that
      with inclusion of this vergence-related region, the frontal eye fields are
      important for all voluntary eye movements.

PMID- 11960811
TI  - Neural basis of disjunctive eye movements.
AB  - New evidence has challenged a widely accepted interpretation of Hering's law of
      equal innervation, which states that disjunctive saccades are produced by the
      linear addition of conjugate and vergence innervation commands produced by
      independent oculomotor subsystems. We hypothesize, instead, that saccades are
      produced by a monocular premotor control network. A model, based on this
      hypothesis and consistent with known brain-stem anatomy, simulates realistic
      disjunctive saccades including initial and late slow vergence movements.

PMID- 11960812
TI  - Population coding in cortical area MST.
AB  - Disparity steps applied to large patterns elicit vergence eye movements at
      ultrashort latencies. Disparity tuning curves, describing the dependence of the
      amplitude of the initial vergence responses on the amplitude of the disparity
      steps, resemble the derivative of a gaussian and indicate that appropriate servo
      like behavior occurs only with small disparity steps (<1 degree). Lesion data
      from monkeys suggest that these vergence responses are mediated, at least in
      part, by neurons in the medial superior temporal area of the cerebral cortex, and
      we here review a recent study of the associated single unit activity in that
      area. Few medial superior temporal neurons have disparity tuning curves whose
      shapes resemble the tuning curve for vergence. Yet, when the disparity tuning
      curves for all of the disparity-sensitive cells recorded from a given monkey are
      summed together, they match the tuning curves for the vergence responses of that
      monkey very closely, even reproducing that animal's idiosyncracies. When all of
      the spike trains elicited by a given disparity step are summed together to give
      an average discharge profile for the whole population of recorded cells, many are
      noisy, but others that are less so match the temporal profile of the motor
      response, vergence velocity, quite well. We conclude that the discharges of the
      disparity-sensitive cells in the medial superior temporal area each represent
      only a very limited aspect of the sensory stimulus (and/or associated motor
      response?), but when pooled together, they provide a complete description of the
      vergence velocity motor response: population coding.

PMID- 11960813
TI  - Adaptive control of vergence in humans.
AB  - Vergence eye alignment minimizes horizontal, vertical, and cyclodisparities to
      optimize stereo-depth perception. Only the horizontal component of vergence is
      under voluntary control. Couplings with voluntary version and horizontal vergence
      guide vertical vergence and cyclovergence. Can these couplings be modified in
      response to sensory demands on binocular vision? We have modified vertical
      vergence and cyclovergence in response to optical changes in disparity. Vertical
      vergence was stimulated with aniseikonic lenses that exaggerated vertical
      disparity in tertiary gaze. Vertical vergence adapted in an hour to produce
      nonconcomitant changes in vertical phoria that varied with vertical eye position
      in tertiary gaze. Cyclovergence was stimulated with cyclodisparities that varied
      with gaze elevation and convergence angle. Cyclovergence adapted within 2 hours
      to produce nonconcomitant changes in cyclophoria that varied with gaze elevation
      and convergence. The adaptive couplings for vertical vergence and cyclovergence
      are modeled as a combination of passive orbital mechanics and active gain control
      of the vertical recti and obliques. Vergence adaptation is a calibration process
      that adjusts the innervation for horizontal, vertical, and torsion components of
      vergence to the physical constraints set by the extraocular muscles and orbital
      connective tissues. Passive orbital mechanics simplify the neural control for
      precise vertical vergence and cyclovergence that are needed to achieve binocular
      alignment under open-loop conditions in response to perceived spatial location.

PMID- 11960814
TI  - Inferior vestibular neuritis.
AB  - Sudden, spontaneous, unilateral loss of vestibular function without simultaneous
      hearing loss or brain stem signs is generally attributed to a viral infection
      involving the vestibular nerve and is called acute vestibular neuritis. The
      clinical hallmarks of acute vestibular neuritis are vertigo, spontaneous
      nystagmus, and unilateral loss of lateral semicircular function as shown by
      impulsive and caloric testing. In some patients with vestibular neuritis the
      process appears to involve only anterior and lateral semicircular function, and
      these patients are considered to have selective superior vestibular neuritis.
      Here we report on two patients with acute vertigo, normal lateral semicircular
      canal function as shown by both impulsive and caloric testing, but selective loss
      of posterior semicircular canal function as shown by impulsive testing and of
      saccular function as shown by vestibular evoked myogenic potential testing. We
      suggest that these patients had selective inferior vestibular neuritis and that
      contrary to conventional teaching, in a patient with acute spontaneous vertigo,
      unilateral loss of lateral semicircular canal function is not essential for a
      diagnosis of acute vestibular neuritis.

PMID- 11960815
TI  - Otolith function: basis for modern testing.
AB  - The major challenge in developing a robust test of otolith function, particularly
      with regard to linear vestibulo-ocular reflex (LVOR) and perceptual measures, is
      to find a way in which graded lesions are reflected in graded response properties
      and abnormalities. The ability of the vestibulo-ocular reflex (VOR) to compensate
      and adapt to dysfunction and pathology presents formidable challenges for
      registering localizing clinical findings, whether in the angular vestibulo-ocular
      reflex (AVOR), the LVOR, or both. Based on a variety of considerations, various
      forms of eccentric rotation seem to provide the most convenient, and potentially
      the most useful, means to generate motion profiles from which otolith function
      can be directly assessed. Both translational and tilt responses can be recorded
      depending on the stimulus profile. The near-centric version is particularly
      enticing because of the ability to study one labyrinth at a time, much like
      calorics. In that case and in others in which the tilt-LVOR is prominent,
      measures of the perceived visual vertical are useful and by all accounts similar
      to ocular torsion. The latter does hold the important advantage of being an
      objective measure, requiring no intervention on the part of the patient. The
      translational-LVOR can be derived from eccentric rotation responses with the head
      displaced forward as well as backward, while viewing near targets in hopes of
      generating a large addition or subtraction (even inversion) of an otherwise AVOR
      driven reflex. These considerations provide an impetus to pursue improved methods
      of quantifying otolith function in a clinical population. The sobering caveat is
      that the diagnosis of total unilateral vestibular loss presents little challenge
      either clinically or by classic testing (e.g., calorics), and yet most of our
      efforts in developing quantifiable measures of dysfunction over the years have
      yielded results that are modest and hardly compelling.

PMID- 11960816
TI  - Vergence-mediated modulation of the human horizontal angular VOR provides
      evidence of pathway-specific changes in VOR dynamics.
AB  - The horizontal vestibulo-ocular reflex (VOR) evoked by passive, high
      acceleration, head-on-body rotations (head thrusts) while viewing a far (124-cm)
      or near (15-cm) target was recorded (scleral search coil) in four subjects with
      normal vestibular function and in one subject with unilateral vestibular
      hypofunction. For responses in the subjects with normal vestibular function, the
      latency of responses relative to the onset of head movement was 7.5 +/- 1.5 ms
      for the VOR and 21.6 +/- 1.2 ms for the vergence-mediated increase in VOR gain.
      The gain of the VOR at the peak of the velocity response while viewing a far
      target was 1.01 +/- 0.06; while viewing a near target, it was 1.25 +/- 0.08 (p
      <0.003). The responses were modeled with two pathways based on the different
      latencies. The "far-viewing" pathway was represented by a constant gain term. The
      "near-viewing" pathway was represented by a first-order lead term, a gain that
      was dependent on viewing distance, and a delay. Analysis of the responses
      revealed that the lead term was greater for the adducting than the abducting eye.
      In the subject with unilateral vestibular hypofunction, ipsilesional responses
      showed no change in VOR gain with respect to viewing distance. Contralesional
      responses retained the vergence-dependent increase in gain. A bilateral model was
      developed based on the data from the subjects with normal vestibular function.
      Simulations of this model when inputs were eliminated from one side predict the
      changes observed in the subject with unilateral vestibular hypofunction. The
      response asymmetries arise because the near-viewing pathway is more susceptible
      to inhibitory cutoff than is the far-viewing pathway.

PMID- 11960817
TI  - Genetics of familial episodic vertigo and ataxia.
AB  - The familial episodic ataxias are prototypical inherited channelopathies that
      result in episodes of vertigo and ataxia triggered by stress and exercise.
      Episodic ataxia type 1 (EA-1) is caused by missense mutations in the potassium
      channel gene KCNA1, whereas episodic ataxia type 2 (EA-2) is caused by missense
      and nonsense mutations in the calcium channel gene CACNA1A. These ion channels
      are crucial for both central and peripheral neurotransmission. Within the last
      few years, the genetic mechanisms underlying these relatively rare familial
      episodic ataxia syndromes have been worked out. They provide a model for
      understanding the mechanisms of more common recurrent vertigo and ataxia
      syndromes, particularly those associated with migraine. Migraine affects as many
      as 15-20% of the general population, and it has been estimated that about 25% of
      patients with migraine experience spontaneous attacks of vertigo and ataxia. We
      identified 24 families with migraine and benign recurrent vertigo inherited in an
      autosomal dominant fashion. These families have numerous features in common with
      EA-1 and EA-2 (particularly EA-2), suggesting that benign recurrent vertigo may
      be an inherited channelopathy. An ion channel mutation shared by brain and inner
      ear could explain the combined central and peripheral features of the syndrome.

PMID- 11960818
TI  - Animal models for visual deprivation-induced strabismus and nystagmus.
AB  - The development of gaze-stabilizing systems depends on normal vision during
      infancy. Monkeys reared with binocular lid suture (BLS) for the first 25-40 days
      of life have strabismus, optokinetic nystagmus deficits, latent nystagmus, and
      decreased binocular cells in the visual cortex and nucleus of the optic tract.
      When BLS is extended to 55 days, pendular and congenital nystagmus also occurs.
      Eyelids in infant monkeys are hairless and thin, but BLS still degrades sensory
      fusion, motion, and form perception. To determine to what extent these visual
      properties are critical in the development of normal gaze stabilization, we
      examined infant monkeys reared with one opaque contact lens over one eye,
      alternated to the fellow eye every other day (AMO); and monkeys reared in a 3-Hz
      strobe environment. Monkeys reared with AMO develop strabismus, but have normal
      optokinetic nystagmus and no spontaneous nystagmus. Area 17 is monocular, but the
      medial temporal area and the nucleus of the optic tract are binocular. Monkeys
      reared in strobe light develop pendular nystagmus but not strabismus. We were
      puzzled by the results of the AMO monkeys until we examined infant monkeys with
      BLS that were prevented from seeing form through the lids. This was done by
      leaving the tarsal plate intact behind the eyelid. They developed similar to the
      AMO monkeys. These results suggest that disruption of sensory fusion during
      infancy (BLS, AMO) causes strabismus. If strabismus occurs while the monkeys have
      some form vision from each eye (BLS without tarsal plate), then the nucleus of
      the optic tract becomes monocular, which causes optokinetic nystagmus deficits
      and latent nystagmus. Infant monkeys reared without visual motion develop
      pendular nystagmus.

PMID- 11960819
TI  - Development of new treatments for congenital nystagmus.
AB  - The use of ocular motor data as the basis for the development of both nonsurgical
      and surgical therapies for congenital nystagmus (CN) has been underway since the
      mid-1960s. This paper presents three nonsurgical therapies (composite prisms,
      soft contact lenses, and afferent stimulation) and a new surgical therapy (four
      muscle tenotomy) hypothesized from analysis of ocular motor data. The expanded
      nystagmus acuity function test was developed to both predict and measure the
      effectiveness of CN therapies and for intersubject comparisons. Base-out prisms
      may be used to damp CN during distance fixation in patients whose CN damps during
      near fixation and who are binocular (i.e., they have no strabismus). Soft contact
      lenses may be used in those whose CN damps with afferent stimulation of the
      ophthalmic division of the trigeminal nerve. Cutaneous afferent stimulation
      (rubbing, vibration, or electricity) of the forehead or neck damps CN in some
      individuals. Finally, as first demonstrated in an achiasmic Belgian sheepdog and
      later in humans, tenotomy of the four horizontal rectus muscles and reattachment
      at their original sites may also damp CN. Taken together, these findings suggest
      the existence of one or more proprioceptive feedback loops acting to change the
      small-signal gain of the extraocular plant. Four-muscle tenotomy provides a
      needed therapeutic option for the many individuals with CN for whom other
      surgical therapies are contraindicated. Tenotomy may also prove useful in see-saw
      nystagmus (it abolished it in the aforementioned canine) or other types of
      nystagmus; further studies of the latter are required.

PMID- 11960820
TI  - A neurobiological approach to acquired nystagmus.
AB  - The development of animal and mathematical models for several forms of acquired
      nystagmus has led to more comprehensive knowledge of these disorders. In the best
      understood forms, such as periodic alternating nystagmus, our range of knowledge
      includes an animal model, the neurotransmitters involved, and effective
      treatment. For some other forms, such as downbeat nystagmus, we have an animal
      model, but reliable treatment is lacking. In other cases, exemplified by acquired
      pendular nystagmus, we have only a provisional hypothesis for pathogenesis to
      account for the oscillations, without an animal model, but effective treatment is
      possible in some patients. The present trend of studying all aspects of the
      neurobiology of nystagmus, from molecules to behavior, seems to be the best
      approach to extend our knowledge and to identify new treatments, but much remains
      to be done.

PMID- 11960821
TI  - Extraocular muscle gene expression and function after dark rearing.

PMID- 11960822
TI  - Conservation of synapse-signaling pathways at the extraocular muscle
      neuromuscular junction.

PMID- 11960823
TI  - Extraocular muscle fatigue.

PMID- 11960825
TI  - Ocular motor myotonic phenomenon in myotonic dystrophy.

PMID- 11960824
TI  - Nitric oxide and cGMP modulation of extraocular muscle contraction.

PMID- 11960826
TI  - Midbrain reticular formation circuitry subserving gaze in the cat.

PMID- 11960827
TI  - Activity in the primate rostral superior colliculus during the "gap effect" for
      pursuit and saccades.

PMID- 11960828
TI  - Time-optimality and the spectral overlap of saccadic eye movements.

PMID- 11960829
TI  - Knowledge of future target position influences saccade-associated head movements.

PMID- 11960830
TI  - Normal and abnormal slowing of saccades: are they one and the same phenomenon?

PMID- 11960831
TI  - Smooth pursuit tracking: saccade amplitude modulation during exposure to
      microgravity.

PMID- 11960832
TI  - Saccadic palsy after cardiac surgery: visual disability and rehabilitation.

PMID- 11960833
TI  - Small vertical saccades have normal speeds in progressive supranuclear palsy
      (PSP).

PMID- 11960834
TI  - Saccadic and vestibular abnormalities in multiple sclerosis: sensitive clinical
      signs of brainstem and cerebellar involvement.

PMID- 11960836
TI  - Anticompensatory eye position ("contraversion") in optokinetic nystagmus.

PMID- 11960835
TI  - A form of inherited cerebellar ataxia with saccadic intrusions, increased
      saccadic speed, sensory neuropathy, and myoclonus.

PMID- 11960837
TI  - Adaptive control of saccades in children with dancing eye syndrome.

PMID- 11960838
TI  - Integration of motion signals for smooth pursuit eye movements.

PMID- 11960839
TI  - Visually driven eye movements elicited at ultra-short latency are severely
      impaired by MST lesions.

PMID- 11960840
TI  - Neuronal activity in monkey cortical area 6 during the initial phase of smooth
      pursuit against a stationary background.

PMID- 11960841
TI  - Perisaccadic occipital EEG changes quantified with wavelet analysis.

PMID- 11960842
TI  - Human gaze shifts to acoustic and visual targets.

PMID- 11960843
TI  - A bayesian approach to change blindness.

PMID- 11960844
TI  - Sensory processing delays measured with the eye-movement correlogram.

PMID- 11960845
TI  - Inhibitory control of saccade generation mediated by various oculomotor regions
      in response to reading difficulty.

PMID- 11960846
TI  - Botulinum toxin therapy for apraxia of lid opening.

PMID- 11960848
TI  - Binocular eye movement responses to dichoptically presented horizontal and/or
      vertical stimulus steps.

PMID- 11960847
TI  - Distinguishing progressive supranuclear palsy from other forms of Parkinson's
      disease: evaluation of new signs.

PMID- 11960849
TI  - Visual processing in disparity vergence control.

PMID- 11960850
TI  - Anticipatory saccadic-vergence responses in humans.

PMID- 11960851
TI  - Vergence eye movements in strabismus patients.

PMID- 11960852
TI  - Vergence disorders in progressive supranuclear palsy.

PMID- 11960853
TI  - A new way to find the primary position in three-dimensional measurements.

PMID- 11960854
TI  - Neural mechanisms of three-dimensional eye and head movements.

PMID- 11960855
TI  - The visuomotor transformation for arm movement accounts for 3-D eye orientation
      and retinal geometry.

PMID- 11960856
TI  - Implementation of Listing's law in patients with unilateral sixth nerve palsy.

PMID- 11960857
TI  - Hyperdeviation and static ocular counterroll in unilateral abducens nerve palsy.

PMID- 11960858
TI  - Vestibulo-ocular responses during mirror-viewing.

PMID- 11960859
TI  - The effects of horizontal head position (yaw axis) and step velocity on the
      vestibulo-ocular reflex.

PMID- 11960860
TI  - The vertical vestibulo-ocular reflex, and visual-vestibular interaction during
      active head motion.

PMID- 11960861
TI  - A three-channel model for generating the vestibulo-ocular reflex in each eye.

PMID- 11960862
TI  - Rectified cross-axis adaptation of the vestibulo-ocular reflex in rhesus monkey.

PMID- 11960863
TI  - Three-dimensional eye-movement responses to surface galvanic vestibular
      stimulation in normal subjects and in patients: a comparison.

PMID- 11960864
TI  - Translational VOR responses to abrupt interaural accelerations in normal humans.

PMID- 11960865
TI  - Rapid adaptation of translational vestibulo-ocular reflex: time course,
      consolidation, and specificity.

PMID- 11960866
TI  - Rapid adaptation of translational vestibulo-ocular reflex: independence of
      retinal slip.

PMID- 11960867
TI  - Effects of a large-field visual scene on the vergence response to naso-occipital
      linear motion in monkeys.

PMID- 11960868
TI  - Dynamic changes of eye cyclo position during head tilt.

PMID- 11960869
TI  - The myth of static ocular counter-rolling: the response of the eyes to head tilt.

PMID- 11960870
TI  - Otolith effect on torsional quick phases of vestibular nystagmus in humans.

PMID- 11960871
TI  - Impaired linear vestibulo-ocular reflex initiation and vestibular catch-up
      saccades in older persons.

PMID- 11960872
TI  - A new differential diagnosis for spontaneous nystagmus: lateral canal
      cupulolithiasis.

PMID- 11960874
TI  - Unilateral rebound nystagmus: one manifestation of two different pathologic
      processes.

PMID- 11960873
TI  - Changes in the angular vestibulo-ocular reflex after a single dose of
      intratympanic gentamicin for Meniere's disease.

PMID- 11960875
TI  - Delayed-onset seesaw nystagmus posttraumatic brain injury with bitemporal
      hemianopia.

PMID- 11960876
TI  - Main sequence of convergence retraction nystagmus indicates a disorder of
      vergence.

PMID- 11960877
TI  - Effects of intravenous opioids on eye movements in humans: possible mechanisms.

PMID- 11960878
TI  - Evaluation of current optical methods for treating the visual consequences of
      nystagmus.

PMID- 11960879
TI  - Latency of dynamic and gaze-dependent optotype recognition in patients with
      infantile Nystagmus syndrome versus control subjects.

PMID- 11960880
TI  - A robust, normal ocular motor system model with latent/manifest latent nystagmus
      and dual-mode fast phases.

PMID- 11960881
TI  - A hypothetical fixation system capable of extending foveation in congenital
      nystagmus.

PMID- 11960882
TI  - Congenital periodic alternating nystagmus: response to baclofen.

PMID- 11960883
TI  - Infections and the risk of relapse in multiple sclerosis.

PMID- 11960884
TI  - The minicolumn hypothesis in neuroscience.
AB  - The minicolumn is a continuing source of research and debate more than half a
      century after it was identified as a component of brain organization. The
      minicolumn is a sophisticated local network that contains within it the elements
      for redundancy and plasticity. Although it is sometimes compared to subcortical
      nuclei, the design of the minicolumn is a distinctive form of module that has
      evolved specifically in the neocortex. It unites the horizontal and vertical
      components of cortex within the same cortical space. Minicolumns are often
      considered highly repetitive, even clone-like, units. However, they display
      considerable heterogeneity between areas and species, perhaps even within a given
      macrocolumn. Despite a growing recognition of the anatomical basis of the
      cortical minicolumn, as well as its physiological properties, the potential of
      the minicolumn has not been exploited in fields such as comparative neuroanatomy,
      abnormalities of the brain and mind, and evolution.

PMID- 11960885
TI  - Prospective study on the relationship between infections and multiple sclerosis
      exacerbations.
AB  - One of the characteristics of multiple sclerosis is the unpredictable occurrence
      of exacerbations and remissions. These fluctuations in disease activity are
      related to alterations in (auto-)immune activity. Exacerbations lead to short
      term morbidity, but may also influence long-term disability. This longitudinal
      study in 73 patients with relapsing-remitting multiple sclerosis assessed the
      contribution of systemic infections to the natural course of exacerbations. In
      addition, we analysed whether infections lead to an increase in the number of
      gadolinium-enhancing lesions. A total of 167 infections and 145 exacerbations
      were observed during 6466 patient weeks. During a predefined at-risk period (ARP)
      of 2 weeks before until 5 weeks after the onset of a clinical infection
      (predominantly upper airway infections), there was an increased risk of
      exacerbations (rate ratio 2.1), which is in accordance with previous studies.
      Exacerbations with onset during the ARP led more frequently to sustained deficit
      [increase of > or =1 Expanded Disability Status Scale (EDSS) point or > or =0.5
      above EDSS 5.5 for >3 months] than exacerbations with onset outside the ARP, with
      a rate ratio of 3.8. Minor and major exacerbations were equally distributed
      between the ARP and non-ARP onset groups. ARP exacerbations were associated with
      significantly higher plasma levels of the inflammatory marker soluble
      intracellular adhesion molecule 1 than non-ARP exacerbations, indicating
      relatively enhanced immune activation during ARP relapses. Three serial MRI scans
      were performed after the onset of an infection over a 6-week period. There was no
      difference in the number of gadolinium-enhancing lesions between the three time
      points. In conclusion, exacerbations in the context of a systemic infection lead
      to more sustained damage than other exacerbations. There is no indication that
      this effect occurs through enhanced opening of the blood-brain barrier.

PMID- 11960886
TI  - The aetiology of sporadic adult-onset ataxia.
AB  - The nosology and aetiology of sporadic adult-onset ataxia are poorly understood.
      The aim of the present study was to answer the following questions: (i) How many
      sporadic ataxia patients have a genetic cause? (ii) How many sporadic ataxia
      patients suffer from multiple system atrophy (MSA)? (iii) Is there a specific
      association between sporadic ataxia and serum anti-glutamic acid decarboxylase
      (GAD) or antigliadin antibodies? and (iv) What are the clinical features of
      patients with unexplained sporadic ataxia? The study was performed in 112
      patients who met the following inclusion criteria: (i) progressive ataxia; (ii)
      onset after 20 years; (iii) informative and negative family history (no similar
      disorders in first- and second-degree relatives; parents older than 50 years);
      and (iv) no established symptomatic cause. Thirty-two patients (29%) met the
      clinical criteria of possible (7%) or probable (22%) MSA. The Friedreich's ataxia
      mutation was found in five patients (4%), the spinocerebellar ataxia (SCA) 2
      mutation in one (1%), the SCA3 mutation in two (2%) and the SCA6 mutation in
      seven (6%). The disease remained unexplained in 65 patients (58%). We did not
      detect anti-GAD antibodies in any of our patients. Antigliadin antibodies were
      present in 14 patients, 10 patients with unexplained ataxia (15%) and 4 patients
      with an established diagnosis (9%). Patients with unexplained sporadic ataxia had
      a median disease onset of 56.0 years. Decreased vibration sense (62%), decreased
      or absent ankle reflexes (40%), increased ankle reflexes (39%), dysphagia (38%)
      and extensor plantar responses and/or spasticity (34%) were the most frequent
      extracerebellar symptoms. Compared with MSA, disease progression was
      significantly slower.

PMID- 11960887
TI  - Pathological, clinical and genetic heterogeneity in progressive supranuclear
      palsy.
AB  - We have identified two groups of patients with clinically typical and atypical,
      pathologically diagnosed progressive supranuclear palsy (PSP), and investigated
      their genetic and molecular pathological characteristics. Those with clinically
      typical PSP are more likely to have the PSP susceptibility genotype and to have
      the deposition of PSP-type hyperphosphorylated tau protein. The clinically
      atypical PSP group contains a number of different clinical syndromes, including
      an L-dopa unresponsive bradykinetic syndrome and a clinical syndrome closely
      resembling idiopathic Parkinson's disease. The clinically atypical PSP group are
      less likely to have the PSP susceptibility genotype and often have the deposition
      of Alzheimer's disease paired helical filament type hyperphosphorylated tau. This
      study suggests that the tau PSP susceptibility genotype is most strongly
      associated with clinically typical PSP. Neurofibrillary tangle parkinsonian
      disorders, which pathologically resemble PSP but involve the deposition of
      Alzheimer's disease-type tau often without involvement of the tau susceptibility
      genotype, need to be distinguished for diagnostic and research purposes.

PMID- 11960888
TI  - Persistence of attacks of cluster headache after trigeminal nerve root section.
AB  - Cluster headache is a strictly unilateral headache that occurs in association
      with cranial autonomic features. We report a patient with a trigeminal nerve
      section who continued to have attacks. A 59-year-old man described a 14-year
      history of left-sided episodes of excruciating pain centred on the retro-orbital
      and orbital regions. These episodes lasted 1-4 h, recurring 2-3 times daily. The
      attacks were associated with ipsilateral ptosis, conjunctival injection,
      lacrimation, rhinorrhoea and facial flushing. From 1986 to 1988, he had trials of
      medications without any benefit. In February 1988, he had complete surgical
      section of the left trigeminal sensory root that shortened the attacks in length
      for 1 month without change in their frequency or character. In April 1988, he had
      further surgical exploration and the root was found to be completely excised;
      post-operatively, there was no change in the symptoms. From 1988 to 1999, he had
      a number of medications, including verapamil and indomethacin, all of which were
      ineffective. Prednisolone 30 mg orally daily rendered the patient completely pain
      free. Sumatriptan 100 mg orally and 6 mg subcutaneously aborted the attack after
      approximately 45 and 15 min, respectively. He was completely anaesthetic over the
      entire left trigeminal distribution. Left corneal reflex was absent. Motor
      function of the left trigeminal nerve was preserved. Neurological and physical
      examination was otherwise normal. MRI scan showed a marked reduction in the
      calibre of the left trigeminal nerve from the nerve root exit zone in the pons to
      Meckel's cave. An ECG-gated three-dimensional multislab MRI inflow angiogram was
      performed. No dilatation was observed in the left internal carotid artery during
      the cluster attack. Blink reflexes were elicited with a standard electrode and
      stimulus. Stimulation of the left supraorbital nerve produced neither ipsilateral
      nor contralateral blink reflex response. Stimulation of the right supraorbital
      nerve produced an ipsilateral response with a mean R2 onset latency of 36 ms and
      a contralateral response with a mean R2 onset latency of 32 ms. Lack of
      ipsilateral vessel dilatation makes the role of vascular factors in the
      initiation of cluster attacks questionable. With complete section of the left
      trigeminal sensory root the brain would perceive neither vasodilatation nor a
      peripheral neural inflammatory process; however, the patient continued to have an
      excellent response to sumatriptan. The case illustrates that cluster headache may
      be generated primarily from within the brain, and that triptans may have anti
      headache effects through an entirely central mechanism.

PMID- 11960889
TI  - Decrease of sympathetic cardiovascular modulation after temporal lobe epilepsy
      surgery.
AB  - In temporal lobe epilepsy (TLE), there is evidence of ictal and interictal
      autonomic dysregulation, predominantly with sympathetic overactivity. The effects
      of TLE surgery on autonomic cardiovascular control and on baroreflex sensitivity
      (BRS) have not been studied. To evaluate such effects, we monitored heart rate
      (HR), systolic blood pressure (BP(sys)) and respiration in 18 TLE patients 3-4
      months before and after TLE surgery. We used Blackman-Tukey spectral analysis to
      assess sympathetic and parasympathetic modulation as powers of HR and BP(sys)
      oscillations in the low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15
      0.5 Hz) bands. BRS was determined as the LF transfer function gain between BP and
      HR. After surgery, HR, BP(sys), respiration and HF powers remained unchanged,
      while LF powers of HR (1.57 +/- 1.54 bpm(2)) and BP(sys) (2.19 +/- 1.34 mmHg(2))
      and BRS (0.68 +/- 0.31 bpm/mmHg) were smaller than pre-surgical LF powers of HR
      (3.87 +/- 3.26 bpm(2)) and BP(sys) (4.80 +/- 3.84 mmHg(2)) and BRS (1.12 +/- 0.39
      bpm/mmHg; P < 0.05). After TLE surgery, there is a reduction of sympathetic
      cardiovascular modulation and BRS that might result from decreased influences of
      interictal epileptogenic discharges on brain areas involved in cardiovascular
      autonomic control. TLE surgery seems to stabilize the cardiovascular control in
      epilepsy patients by reducing the risk of sympathetically mediated
      tachyarrhythmias and excessive bradycardiac counter-regulation, both of which
      might be relevant for the pathophysiology of sudden unexpected death in epilepsy
      patients (SUDEP). Thus, TLE surgery might contribute to reducing the risk of
      SUDEP.

PMID- 11960890
TI  - Occurrence and characterization of peripheral nerve involvement in
      neurofibromatosis type 2.
AB  - Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder
      characterized by the occurrence of bilateral vestibular schwannomas, various
      brain and spinal tumours as well as peripheral nerve tumours, cutaneous tumours
      and juvenile posterior lenticular opacity. NF2 is caused by mutations in both
      alleles of a tumour suppressor gene coding for a protein called schwannomin or
      merlin. It is suggested that the development of NF2 tumours is caused by complete
      inactivation of the merlin/schwannomin gene. Interestingly, in a NF2 mouse model,
      peripheral nerve pathology was more frequently described than schwannomas.
      However, review of the literature shows that patients suffering from NF2 seldom
      have unexplained clinical features of peripheral nerve lesion unrelated to tumour
      masses. Single case reports describe sural nerve biopsies, which histologically
      show onion-bulb-like formations, seemingly originating from Schwann cells. We
      have conducted a systematic investigation to determine the occurrence and
      aetiology of peripheral nerve involvement in NF2 patients. We investigated 15
      patients with definite NF2 and in 10 of these found electrophysiological evidence
      of neuropathy. In this study we present the classification of neuropathy,
      correlation to clinical findings, and histological findings of a sural nerve
      biopsy. We conclude that peripheral neuropathy, mostly of axonal type, is a
      common clinical finding in NF2. We hypothesize that the aetiology of this
      frequent peripheral neuropathy syndrome in NF2 is caused by compression effects
      of multiple tumourlets, originating along the length of the peripheral nerves on
      adjacent nerve fibres, by local influences of the endoneurial pathological cells
      on adjacent nerve fibres and/or the inability of these cells to properly adhere
      to, or ensheath, the axon.

PMID- 11960891
TI  - A newly identified chromosomal microdeletion and an N-box mutation of the AChR
      epsilon gene cause a congenital myasthenic syndrome.
AB  - Congenital myasthenic syndromes (CMSs) are frequently caused by mutations of the
      coding region of the acetylcholine receptor epsilon subunit (AChRepsilon) gene
      leading to a reduced expression of the acetylcholine receptor (AChR) at the
      postsynaptic membrane. Two recent observations have linked two different N-box
      mutations of the human AChRepsilon promoter to a clinical CMS phenotype. N-boxes
      are regulatory sequence elements of mammalian promoters that confer synapse
      specific expression of several genes, including the AChR subunit genes. Here, we
      report on a novel point mutation (epsilon-154G-->A) in the N-box of the
      AChRepsilon promoter in a German CMS pedigree. Semiquantitative analysis of
      AChRepsilon mRNA levels in the patient's muscle indicated significantly impaired
      AChRepsilon expression. We provide additional evidence of a pathogenic role for
      this mutation using the mutated promoter (epsilon-154G-->A) driving a
      heterologous gene (luciferase) in rat skeletal muscle. We show that agrin-induced
      gene expression is significantly reduced by the N-box mutant (mt) compared with
      the wild-type (wt) promoter. Refined haplotype analysis and direct sequencing
      revealed maternal inheritance of the mutant AChRepsilon promoter (epsilon-154G-
      >A) together with paternal inheritance of a chromosomal microdeletion (Delta1290
      bp) encompassing the promoter and the first two exons of the AChRepsilon gene in
      the index patient. In conclusion, we provide genetic and functional evidence that
      a mutation of the AChRepsilon subunit promoter (epsilon-154G-->A) causes CMS due
      to the reduction of gene expression in skeletal muscle. Moreover, this is the
      first report of a chromosomal microdeletion affecting an AChR gene. This type of
      mutation may be missed in standard screening techniques of CMS patients.

PMID- 11960892
TI  - Brain activation and sexual arousal in healthy, heterosexual males.
AB  - Despite the brain's central role in sexual function, little is known about
      relationships between brain activation and sexual response. In this study, we
      employed functional MRI (fMRI) to examine relationships between brain activation
      and sexual arousal in a group of young, healthy, heterosexual males. Each subject
      was exposed to two sequences of video material consisting of explicitly erotic
      (E), relaxing (R) and sports (S) segments in an unpredictable order. Data on
      penile turgidity was collected using a custom-built pneumatic pressure cuff. Both
      traditional block analyses using contrasts between sexually arousing and non
      arousing video clips and a regression using penile turgidity as the covariate of
      interest were performed. In both types of analyses, contrast images were computed
      for each subject and these images were subsequently used in a random effects
      analysis. Strong activations specifically associated with penile turgidity were
      observed in the right subinsular region including the claustrum, left caudate and
      putamen, right middle occipital/ middle temporal gyri, bilateral cingulate gyrus
      and right sensorimotor and pre-motor regions. Smaller, but significant activation
      was observed in the right hypothalamus. Few significant activations were found in
      the block analyses. Implications of the findings are discussed. Our study
      demonstrates the feasibility of examining brain activation/sexual response
      relationships in an fMRI environment and reveals a number of brain structures
      whose activation is time-locked to sexual arousal.

PMID- 11960893
TI  - Posterior parietal cortex is implicated in continuous switching between verbal
      fluency tasks: an fMRI study with clinical implications.
AB  - We investigated whether posterior parietal cortex controls attentional switching
      when the tasks involve neither spatial nor visual cognition. Normal volunteers
      were scanned using functional MRI (fMRI). In all conditions, subjects were
      required to covertly produce words in verbal fluency tasks. They did so at a rate
      of one every 2 s (with eyes closed) in response to an auditory beep. In the non
      switching (NS) trials, subjects responded with a series of items from a
      prespecified semantic category (SC) (e.g. fruits or cars) and from overlearned
      sequences (OSs) (days of the week, months of the year or letters of the
      alphabet). Instructions as to which category items should be drawn from on a
      given run of trials were presented over fMRI-compatible earphones prior to each
      run. In the switching (S) trials, subjects produced a series of word triads from
      three SCs: for example, fruits, cars and furniture (e.g. pear, Mercedes, table.);
      and from three OSs: days of the week, months of the year and letters of the
      alphabet (e.g. Monday, January, A.). This design is factorial, with the factors
      verbal class (SC or OSs) and switching conditions (S or NS). Increases in neural
      activity (P < 0.05, corrected for multiple comparisons) were observed only in
      superior posterior parietal cortex bilaterally as a main effect of the S
      conditions compared with the NS conditions. When SC fluency was compared with OS
      fluency, significant activations were found in anterior cingulate cortex
      bilaterally, the left inferior frontal gyrus, the middle frontal gyrus
      bilaterally, frontal operculum bilaterally and in the cerebellar vermis. These
      results support the hypothesis that superior posterior parietal cortex is a
      supramodal area implicated in task switching, even when no visual or spatial
      component is implicated in the tasks. Task switching, frequently used to examine
      'frontal' executive functions, may also be clinically relevant to the assessment
      of patients with superior posterior parietal lesions.

PMID- 11960894
TI  - Sound localization in callosal agenesis and early callosotomy subjects: brain
      reorganization and/or compensatory strategies.
AB  - In order to evaluate the callosal involvement in sound localization, the present
      study examined the response accuracy of acallosal and early callosotomized
      subjects to monaural and binaural auditory targets presented in three-dimensional
      space. In these subjects, bilateral localization cues, such as interaural time
      and level differences, are integrated at the cortical and subcortical levels
      without the additional support of the callosal commissure. Because acallosal and
      early-callosotomized subjects have developed with this reduced source of binaural
      activation of cortical cells, they might have perfected their ability to use
      monaural sound localization cues. This hypothesis was tested by assessing
      localization performance under both binaural and monaural listening conditions.
      Five subjects with callosal agenesis, one callosotomized subject operated early
      in life and 19 control subjects were asked to localize broad-band noise bursts
      (BBNBs) of fixed intensity in the horizontal plane in an anechoic chamber. BBNBs
      were delivered through randomly selected loudspeakers. Two conditions were
      tested: (i) localization of a stationary sound source; and (ii) localization of a
      moving sound source. Listeners had to report the apparent stimulus location by
      pointing to its perceived position on a graduated perimeter. The results
      indicated that the acallosal subjects were less accurate than controls, but only
      in the binaural moving sound condition. More interestingly, in the monaural
      testing conditions, some of the acallosal subjects and the early-callosotomized
      subject performed significantly better than control subjects. This suggests that,
      because of the absence of the corpus callosum, these subjects compensate for
      their reduced access to cortically determined binaural cues by making more
      efficient use of monaural cues.

PMID- 11960895
TI  - Language-specific tuning of visual cortex? Functional properties of the Visual
      Word Form Area.
AB  - The first steps in the process of reading a printed word belong to the domain of
      visual object perception. They culminate in a representation of letter strings as
      an ordered set of abstract letter identities, a representation known as the
      Visual Word Form (VWF). Brain lesions in patients with pure alexia and functional
      imaging data suggest that the VWF is subtended by a restricted patch of left
      hemispheric fusiform cortex, which is reproducibly activated during reading. In
      order to determine whether the operation of this Visual Word Form Area (VWFA)
      depends exclusively on the visual features of stimuli, or is influenced by
      language-dependent parameters, brain activations induced by words, consonant
      strings and chequerboards were compared in normal subjects using functional MRI
      (fMRI). Stimuli were presented in the left or right visual hemifield. The VWFA
      was identified in both a blocked-design experiment and an event-related
      experiment as a left-hemispheric inferotemporal area showing a stronger
      activation to alphabetic strings than to chequerboards, and invariant for the
      spatial location of stimuli. In both experiments, stronger activations of the
      VWFA to words than to strings of consonants were observed. Considering that the
      VWFA is equally activated by real words and by readable pseudowords, this result
      demonstrates that the VWFA is initially plastic and becomes attuned to the
      orthographic regularities that constrain letter combination during the
      acquisition of literacy. Additionally, the use of split-field stimulation shed
      some light on the cerebral bases of the classical right visual field (RVF)
      advantage in reading. A left occipital extrastriate area was found to be
      activated by RVF letter strings more than by chequerboards, while no symmetrical
      region was observed in the right hemisphere. Moreover, activations in the
      precuneus and the left thalamus were observed when subjects were reading RVF
      versus left visual field (LVF) words, and are likely to reflect the attentional
      component of the RVF advantage.

PMID- 11960896
TI  - Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese
      patients.
AB  - We investigated the disease progression and survival in 230 Japanese patients
      with multiple system atrophy (MSA; 131 men, 99 women; 208 probable MSA, 22
      definite; mean age at onset, 55.4 years). Cerebellar dysfunction (multiple system
      atrophy-cerebellar; MSA-C) predominated in 155 patients, and parkinsonism
      (multiple system atrophy-parkinsonian; MSA-P) in 75. The median time from initial
      symptom to combined motor and autonomic dysfunction was 2 years (range 1-10).
      Median intervals from onset to aid-requiring walking, confinement to a
      wheelchair, a bedridden state and death were 3, 5, 8 and 9 years, respectively.
      Patients manifesting combined motor and autonomic involvement within 3 years of
      onset had a significantly increased risk of not only developing advanced disease
      stage but also shorter survival (P < 0.01). MSA-P patients had more rapid
      functional deterioration than MSA-C patients (aid-requiring walking, P = 0.03;
      confinement to a wheelchair, P < 0.01; bedridden state, P < 0.01), but showed
      similar survival. Onset in older individuals showed increased risk of confinement
      to a wheelchair (P < 0.05), bedridden state (P = 0.03) and death (P < 0.01).
      Patients initially complaining of motor symptoms had accelerated risk of aid
      requiring walking (P < 0.01) and confinement to a wheelchair (P < 0.01) compared
      with those initially complaining of autonomic symptoms, while the time until
      confinement to a bedridden state and survival were no worse. Gender was not
      associated with differences in worsening of function or survival. On MRI, a
      hyperintense rim at the lateral edge of the dorsolateral putamen was seen in
      34.5% of cases, and a 'hot cross bun' sign in the pontine basis (PB) in 63.3%.
      These putaminal and pontine abnormalities became more prominent as MSA-P and MSA
      C features advanced. The atrophy of the cerebellar vermis and PB showed a
      significant correlation particularly with the interval following the appearance
      of cerebellar symptoms in MSA-C (r = 0.71, P < 0.01, r = 0.76 and P < 0.01,
      respectively), but the relationship between atrophy and functional status was
      highly variable among the individuals, suggesting that other factors influenced
      the functional deterioration. Atrophy of the corpus callosum was seen in a
      subpopulation of MSA, suggesting hemispheric involvement in a subgroup of MSA
      patients. The present study suggested that many factors are involved in the
      progression of MSA but, most importantly, the interval from initial symptom to
      combined motor and autonomic dysfunction can predict functional deterioration and
      survival in MSA.

PMID- 11960898
TI  - Subcortical aphasia and neglect in acute stroke: the role of cortical
      hypoperfusion.
AB  - We have hypothesized that most cases of aphasia or hemispatial neglect due to
      acute, subcortical infarct can be accounted for by concurrent cortical
      hypoperfusion. To test this hypothesis, we demonstrate: (i) that pure subcortical
      infarctions are associated with cortical hypoperfusion in subjects with
      aphasia/neglect; (ii) that reversal of cortical hypoperfusion is associated with
      resolution of the aphasia; and (iii) that aphasia/neglect strongly predicts
      cortical ischaemia and/or hypoperfusion. We prospectively evaluated a consecutive
      series of 115 patients who presented within 24 h of onset or progression of
      stroke symptoms, with MRI sequences including diffusion weighted imaging (DWI)
      and perfusion weighted imaging (PWI), and detailed testing for aphasia or
      hemispatial neglect. The association between aphasia or neglect and cortical
      infarct (or dense ischaemia) on DWI and cortical hypoperfusion indicated by PWI,
      was evaluated with chi-squared analyses. Fisher exact tests were used for
      analyses with small samples. Cases of DWI lesion restricted to subcortical white
      matter and/or grey matter structures (n = 44) were examined for the presence of
      aphasia or neglect, and for the presence of cortical hypoperfusion. In addition,
      subjects who received intervention to restore perfusion were evaluated with DWI,
      PWI, and cognitive tests before and after intervention. Finally, the positive
      predictive value of the cognitive deficits for identifying cortical abnormalities
      on DWI and PWI were calculated from all patients. Of the subjects with only
      subcortical lesions on DWI in this study (n = 44), all those who had aphasia or
      neglect showed concurrent cortical hypoperfusion. Among the patients who received
      intervention that successfully restored cortical perfusion, 100% (six out of six)
      showed immediate resolution of aphasia. In the 115 patients, aphasia and neglect
      were much more strongly associated with cortical hypoperfusion (chi(2) = 57.3 for
      aphasia; chi(2) = 28.7 for neglect; d.f. = 1; P < 0.000001 for each), than with
      cortical infarct/ischaemia on DWI (chi(2) = 8.5 for aphasia; chi(2) = 9.7 for
      neglect; d.f. = 1; P < 0.005 for each). Aphasia showed a much higher positive
      predictive value for cortical abnormality on PWI (95%) than on DWI (62%), as did
      neglect (100% positive predictive value for PWI versus 74% for DWI). From these
      data we conclude that aphasia and neglect due to acute subcortical stroke can be
      largely explained by cortical hypoperfusion.

PMID- 11960897
TI  - Seizures and raised intracranial pressure in Vietnamese patients with Japanese
      encephalitis.
AB  - Japanese encephalitis (JE) causes at least 10 000 deaths each year. Death is
      presumed to result from infection, dysfunction and destruction of neurons. There
      is no antiviral treatment. Seizures and raised intracranial pressure (ICP) are
      potentially treatable complications, but their importance in the pathophysiology
      of JE is unknown. Between 1994 and 1997 we prospectively studied patients with
      suspected CNS infections referred to an infectious disease referral hospital in
      Ho Chi Minh City, Vietnam. We diagnosed Japanese encephalitis virus (JEV), using
      antibody detection, culture of serum and CSF, and immunohistochemistry of autopsy
      material. We observed patients for seizures and clinical signs of brainstem
      herniation, measured CSF opening pressures (OP) and, on a subset of patients,
      performed EEGs. Of 555 patients with suspected CNS infections, 144 (26%) were
      infected with JEV (134 children and 10 adults). Seventeen (12%) patients died and
      33 (23%) had severe sequelae. Of the 40 patients with witnessed seizures, 24
      (62%) died or had severe sequelae, compared with 26 (14%) of 104 with no
      witnessed seizures [odds ratio (OR) 4.50, 95% confidence interval (CI) 1.94
      10.52, P < 0.0001]. Patients in status epilepticus (n = 25), including 15 with
      subtle motor seizures, were more likely to die than those with other seizures (P
      = 0.003). Patients with seizures were more likely to have an elevated CSF OP (P =
      0.033) and to develop brainstem signs compatible with herniation syndromes (P <
      0.0001). Of 11 patients with CSF OP > or =25 cm, five (46%) died, compared with
      seven (9%) of 80 patients with lower pressures [OR 8.69, 95% CI 1.73-45.39, P =
      0.005). Of the 50 patients with a poor outcome, 35 (70%) had signs compatible
      with herniation syndromes (including 19 with signs of rostro-caudal progression),
      compared with nine (10%) of those with better outcomes (P < 0.0001). Of 11
      patients with CSF OP > or =25 cm, five (46%) died, compared with seven (9%) of 80
      patients with lower pressures (OR 8.69, 95% CI 1.73-45.39, P = 0.005). The
      combination of coma, multiple seizures, brainstem signs and illness for 7 or more
      days was an accurate predictor of outcome, correctly identifying 42 (84%) of 50
      patients with a poor outcome and 82 (87%) of 94 with a better outcome. These
      findings suggest that in JE, seizures and raised ICP may be important causes of
      death. The outcome may be improved by measures aimed at controlling these
      secondary complications.

PMID- 11960899
TI  - Human regional cerebral glucose metabolism during non-rapid eye movement sleep in
      relation to waking.
AB  - Sleep is an essential human function. Although the function of sleep has
      generally been regarded to be restorative, recent data indicate that it also
      plays an important role in cognition. The neurobiology of human sleep is most
      effectively analysed with functional imaging, and PET studies have contributed
      substantially to our understanding of both rapid eye movement (REM) and non-rapid
      eye movement (NREM) sleep. In this study, PET was used to determine patterns of
      regional glucose metabolism in NREM sleep compared with waking. We hypothesized
      that brain structures related to waking cognitive function would show a
      persistence of function into the NREM sleep state. Fourteen healthy subjects (age
      range 21-49 years; 10 women, 4 men) underwent concurrent EEG sleep studies and
      [(18)F]fluoro-2-deoxy-D-glucose PET scans during waking and NREM sleep. Whole
      brain glucose metabolism declined significantly from waking to NREM sleep.
      Relative decreases in regional metabolism from waking to NREM sleep occurred in
      wide areas of frontal, parietal, temporal and occipital association cortex,
      primary visual cortex, and in anterior/dorsomedial thalamus. After controlling
      for the whole-brain declines in absolute metabolism, relative increases in
      regional metabolism from waking to NREM were found bilaterally in the dorsal
      pontine tegmentum, hypothalamus, basal forebrain, ventral striatum, anterior
      cingulate cortex and extensive regions of the mesial temporal lobe, including the
      amygdala and hippocampus, and in the right dorsal parietal association cortex and
      primary somatosensory and motor cortices. The reductions in relative metabolism
      in NREM sleep compared with waking are consistent with prior findings from blood
      flow studies. The relative increases in glucose utilization in the basal
      forebrain, hypothalamus, ventral striatum, amygdala, hippocampus and pontine
      reticular formation are new observations that are in accordance with the view
      that NREM sleep is important to brain plasticity in homeostatic regulation and
      mnemonic processing.

PMID- 11960900
TI  - The neural substrates of episodic memory impairment in Alzheimer's disease as
      revealed by FDG-PET: relationship to degree of deterioration.
AB  - In a previous investigation, we raised the hypothesis that in Alzheimer's disease
      the cerebral structures implicated in episodic memory deficits may differ
      according to the severity of cognitive impairment. To test this hypothesis, Story
      Recall test scores and PET measurements of resting cerebral glucose utilization,
      a measure of synaptic integrity, were obtained in 40 patients. Using SPM96
      (statistical parametric mapping 1996), positive correlations between the two sets
      of data were calculated on a voxel basis, first in the whole patient sample and
      then separately in the two subgroups of 20 patients differing in Mini-Mental
      State Examination score, i.e. those with least impaired and those with most
      impaired performance ('less severe' and 'more severe' subgroups, respectively).
      In the whole sample, significant correlations (P < 0.05, corrected for multiple
      tests) involved bilaterally not only several limbic structures (the
      hippocampal/rhinal cortex regions, posterior cingulate gyrus and retrosplenial
      cortex) but also, and less expectedly, some temporo-occipital association areas.
      However, the subgroup analysis disclosed that, in the less severe subgroup, all
      significant correlations (P < 0.005, uncorrected) were restricted to the
      parahippocampal gyrus and retrosplenial cortex, in accordance with both the
      distribution of changes in tau in early Alzheimer's disease and the known
      involvement of this network in normal and impaired memory function, while in the
      more severe subgroup they mainly involved the left temporal neocortex, which is
      known to be implicated in semantic memory. These findings suggest that, when
      episodic memory is mildly impaired, limbic functions are still sufficient to
      subserve the remaining performance, whereas with more severe memory deficit
      resulting from accumulated pathology the neocortical areas that are normally
      involved in semantic memory are recruited, perhaps as a form of (inadequate)
      compensatory mechanism.

PMID- 11960901
TI  - Dynamics of visual feature analysis and object-level processing in face versus
      letter-string perception.
AB  - Neurones in the human inferior occipitotemporal cortex respond to specific
      categories of images, such as numbers, letters and faces, within 150-200 ms. Here
      we identify the locus in time when stimulus-specific analysis emerges by
      comparing the dynamics of face and letter-string perception in the same 10
      individuals. An ideal paradigm was provided by our previous study on letter
      strings, in which noise-masking of stimuli revealed putative visual feature
      processing at 100 ms around the occipital midline followed by letter-string
      specific activation at 150 ms in the left inferior occipitotemporal cortex. In
      the present study, noise-masking of cartoon-like faces revealed that the response
      at 100 ms increased linearly with the visual complexity of the images, a result
      that was similar for faces and letter-strings. By 150 ms, faces and letter
      strings had entered their own stimulus-specific processing routes in the inferior
      occipitotemporal cortex, with identical timing and large spatial overlap.
      However, letter-string analysis lateralized to the left hemisphere, whereas face
      processing occurred more bilaterally or with right-hemisphere preponderance. The
      inferior occipitotemporal activations at approximately 150 ms, which take place
      after the visual feature analysis at approximately 100 ms, are likely to
      represent a general object-level analysis stage that acts as a rapid gateway to
      higher cognitive processing.

PMID- 11960902
TI  - Morphometry of human superficial dorsal and dorsolateral column fibres:
      significance to spinal cord stimulation.
AB  - In spinal cord stimulation (SCS) large diameter cutaneous (Abeta) fibres in the
      dorsal columns (DCs) are activated and have an inhibiting effect on the
      transmission of pain signals by Adelta and C fibres from the corresponding
      dermatome(s). The largest Abeta fibres can be activated up to a maximum depth of
      about 0.25 mm in the DCs. No data are available on the distribution of the large
      fibres in this superficial human DC layer at the common SCS levels Th(10-11).
      Such data are indispensable to improve the predictive capability of a computer
      model of SCS. The whole myelinated fibre population in the superficial 300 microm
      of the dorsal column (DC(0-300)) at Th(10-11 )of two human subjects was
      morphometrically analysed. Some data was obtained from a third subject. The
      superficial dorsolateral column (DLC(0-300)) was included in this analysis
      because it was hypothesized that large dorsal spinocerebellar tract fibres could
      also be activated by SCS. Only very few fibres larger than 10.7 microm were
      found: a mean of 68 (0.5%) in DC(0-300) and 114 (2%) in DLC(0-300). Considering
      that the effect of SCS is primarily attributed to activation of these largest
      fibres, it is concluded that a surprisingly small average amount of 2.4 fibres
      per running 0.1 mm width and 6 fibres per segmental division of the DC is
      involved. Distinct mediolateral heterogeneity in fibre composition was found in
      both DC(0-300) and DLC(0-300). In the DC(0-300), the mean diameter of fibres > or
      =7.1 microm increases significantly by 5% from medial to lateral. Density (i.e.
      number of fibres per 1000 microm(2)) and frequency (i.e. percentage of a fibre
      size group compared to its parent population) of the large fibres increase
      significantly from medial to lateral in the DC(0-300). For fibres > or =10.7
      microm, these parameters increase by 200 and 269%, respectively. It is concluded
      that the difference in stimulation threshold of large Abeta fibres in the median
      and lateral DC can be mainly attributed to the absence and presence,
      respectively, of collaterals at the stimulation site. Marked differences were
      found between DC(0-300) and DLC(0-300). The largest DLC(0-300) fibres (> or =10.7
      microm) have a 320% higher frequency and a 473% higher density. Their mean
      diameter is, however, only 2% larger. The largest DLC(0-300) fibres are not
      likely to be recruited by SCS, since they are not larger than their DC(0-300)
      counterparts, they lack collaterals (which would reduce the threshold stimulus
      substantially) and they are more remote from the stimulation electrode.

PMID- 11960903
TI  - Interlimb reflexes and synaptic plasticity become evident months after human
      spinal cord injury.
AB  - Persons with long-standing injury to the cervical spinal cord resulting in
      complete or partial paralysis typically develop a wide spectrum of involuntary
      movements in muscles receiving innervation caudal to the level of injury. We have
      previously shown that these movements include brief and discrete contraction of
      muscles in the hand and forearm in response to innocuous sensory stimulation to
      the feet and legs, but we have been unable to replicate these interlimb reflexes
      in able- bodied subjects. Properties of these muscle responses indicate that the
      synaptic contacts between ascending sensory fibres and motor neurones of the
      cervical enlargement are more efficacious than normal. If these connections are
      present at all times, and require the more rostrally-placed spinal cord injury to
      allow their emergence, one might expect their appearance relatively soon
      following injury, as has been shown for studies of 'latent' synapses. Conversely,
      delayed appearance of these interlimb reflexes would suggest either the
      development of new synaptic connections or a profound strengthening of existing
      circuits in the cervical spinal cord due to a combination of afferent target loss
      and motor neurone denervation from motor tracts originating rostral to the injury
      site. In this study, we used repeated examinations of persons with acute injury
      to the cervical spinal cord to examine the time post-injury at which interlimb
      reflexes are first seen. Using tibial nerve stimulation at the knee as a
      screening test, a total of 24 subjects were found to develop interlimb reflexes
      following spinal cord injury. Latencies between stimulation and EMG were as brief
      as 32 ms for muscles of the forearm and 44 ms for muscles in the hand. These
      minimal delays all but rule out a supraspinal route for these interlimb reflexes.
      Interlimb reflexes first became evident no sooner than approximately 6 months
      following injury, and in some individuals were not seen until well over 1 year
      post-injury. Enhanced lower limb segmental excitability had emerged in nearly all
      of these subjects weeks or months prior to the first appearance of interlimb
      reflexes, arguing against a manifestation of traditional post-traumatic
      spasticity as a basis for this activity. This prolonged delay between time of
      injury and emergence of interlimb reflex activity lends support to the hypothesis
      that this activity represents an example of plasticity-and perhaps 'regenerative
      sprouting'-in the human spinal cord following traumatic injury.

PMID- 11960904
TI  - p53-Mdm2--the affair that never ends.
AB  - The p53-Mdm2 paradigm represents the best-studied relationship between a tumor
      suppressor gene which functions as a transcription factor and an oncogene, which
      functions primarily as an E3 protein ligase. The intimate relationship between
      these two partners has expanded to include almost every cellular biological
      system - from development, to growth control and programmed cell death. The
      affair between Mdm2 and p53 is closely controlled by a complex array of post
      translational modifications, which in turn dictates the stability and activity of
      p53 and Mdm2. Functional diversity depends on the association with a large subset
      of partner proteins, which dictates the type of activity and corresponding
      selectivity. Here we summarize the current understanding of post-translational
      modifications and their effect on conformation-based functional relationship
      between Mdm2 and p53, as it pertains to their diverse cellular biological
      functions.

PMID- 11960905
TI  - Effect of wild-type, S15D and R175H p53 proteins on DNA end joining in vitro:
      potential mechanism of DNA double-strand break repair modulation.
AB  - Balanced regulation of DNA double-strand break (DSB) repair is crucial for
      genetic integrity and cell survival. Cells perform DSB repair either by
      homologous recombination (HR) or by non-homologous end joining (NHEJ). Either
      option carries risk for DNA instability. The presence in the cell of the tumour
      suppressor p53 has been shown to suppress the levels of HR; however, the effect
      of p53 on DNA EJ is less well understood. Here we demonstrate dramatically
      increased DNA EJ activity in cell-free extracts from p53(-/-) mouse embryo
      fibroblasts (MEFs) compared with p53(+/+) MEFs. The addition of wild-type (wt)
      p53 to p53(-/-) MEFs extracts inhibited DNA EJ in a dose-dependent manner.
      Binding of wt p53 to DNA ends in vitro protected them from exonuclease attack and
      inhibited T4 DNA ligase-dependent EJ. This inhibitory effect was markedly
      enhanced for p53 R175H, a cancer-derived mutant of p53. In contrast, inhibition
      was negated in the presence of p53 S15D, a phosphorylation-mimicking mutant
      protein. Interestingly, p53 S15D stimulated in vitro DNA EJ of the blunt-ended
      DNA by T4 DNA ligase. Here we discuss the possibility that, in conjunction with
      its ability to control levels of HR, p53 may also serve to suppress DNA EJ in
      cells under normal conditions. This suppression may be associated with DNA
      dependent protein kinases or ATM kinases, providing potential crosstalk between
      major cellular pathways of DNA repair and cell-cycle checkpoint mechanisms.

PMID- 11960906
TI  - Hypermethylation of the imprinted NNAT locus occurs frequently in pediatric acute
      leukemia.
AB  - Recent studies have demonstrated imprinting of the human neuronatin (NNAT) gene.
      NNAT maps to 20q11.2-q12, a region exhibiting loss of heterozygosity in acute
      myeloid leukemia and myelodysplastic/myeloproliferative disease. To investigate
      possible epigenetic dysregulation of genes in this region relevant to
      leukemogenesis, we analyzed methylation of the NNAT gene in normal tissues and in
      leukemias. We found a differential methylation pattern, typical of imprinted
      genes, at sites in the CpG island containing NNAT exon 1 in normal pituitary,
      peripheral blood cells and bone marrow-derived CD34-positive hematopoietic
      progenitor cells. Substantial or complete loss of the unmethylated NNAT allele
      was observed in leukemia cell lines and in 20 of 29 (69%) acute myeloid or
      lymphoid leukemia samples. While most highly expressed in brain, NNAT mRNA was
      also detected in normal hematopoietic progenitor cells and in leukemia cells
      exhibiting the normal methylation pattern, although not in hypermethylated
      leukemia cells. Demethylation by treatment of hypermethylated leukemia cells with
      5-aza-2'-deoxycytidine resulted in reactivation of NNAT expression, concomitant
      with a reversion to the normal methylation pattern. The data demonstrate that
      hypermethylation of the NNAT locus is a frequent event in both myeloid and
      lymphoid acute leukemias of childhood. Aberrant hypermethylation of the NNAT
      locus suggests that the dysregulation of genes at 20q11.2-q12 in leukemia may be
      the result of epigenetic as well as genetic events.

PMID- 11960907
TI  - Malignant conversion of non-tumorigenic murine skin keratinocytes overexpressing
      PACE4.
AB  - Proprotein convertases (PCs) have been implicated in tumor cell invasion by
      processing a variety of substrates including matrix metalloproteinases (MMPs).
      PACE4, a member of the family of PCs was shown to enhance mouse skin carcinoma
      progression by increasing tumor cell invasiveness. However, the effects of PACE4
      on malignant conversion have not been investigated. In the present study we
      address the possible role of PACE4 as a trigger of malignant conversion by
      transfecting with a full-length PACE4 cDNA, three keratinocyte cell lines with no
      or little tumorigenic potential, i.e. non-tumorigenic BALB/MK-2 cells,
      tumorigenic non-invasive MT1/2 cells and tumorigenic moderately invasive p117
      mouse skin keratinocytes. Overexpression of PACE4 led to a significant increase
      in the processing of stromelysin-3, a well-characterized substrate of this PC.
      When assayed for invasive ability, the PACE4-transfected cells were invasive both
      in vitro and in vivo, whereas their control counterparts were not. In addition,
      an enhanced processing ability of MT2-MMP a known substrate of PCs was detected
      in the PACE4-transfected cells. This was accompanied by MMP-2 and MMP-9
      activation in PACE4 transfectants. Invasion and MMP processing were remarkably
      reduced when PACE4 was inhibited with a specific antibody. By triggering the
      processing of crucial invasion-related proteases, PACE4 is not only able to
      enhance the invasive ability of malignant cells as demonstrated previously, but
      also played a significant role in converting non-invasive keratinocytes into
      malignant cells.

PMID- 11960909
TI  - Growth inhibition, cell-cycle arrest and apoptosis in human T-cell leukemia by
      the isothiocyanate sulforaphane.
AB  - Glucosinolates (GL) can inhibit, retard or reverse experimental multistage
      carcinogenesis. When brassica plant tissue is broken, GLs are hydrolyzed by the
      endogenous enzyme myrosinase (Myr), releasing many products including
      isothiocyanates (ITC). Synthetic ITCs like sulforaphane exert chemopreventive
      effects against chemically induced tumors in animals, modulating enzymes required
      for carcinogens' activation/detoxification and/or the induction of cell-cycle
      arrest and apoptosis in tumor cell lines. To investigate the chemopreventive
      potential of ITCs while reproducing the circumstances of dietary contact with
      sulforaphane, we studied proliferation, apoptosis induction and p53, bcl-2 and
      bax protein expression in Jurkat T-leukemia cells by sulforaphane, the ITC
      generated in situ in a quantitative manner by Myr starting from glucoraphanin
      (GRA). Jurkat cells were treated with different doses of GRA-Myr mixture. Effects
      on cell growth or survival were evaluated by counting trypan blue-excluding
      cells. Cell-cycle progression, apoptosis and expression of p53, bax and bcl-2
      proteins were analyzed by flow cytometry. Results were analyzed by two-sided
      Fisher's exact test. Sulforaphane, but not GRA, caused G(2)/M-phase arrest (P =
      0.028) and increase of apoptotic cell fraction (P < 0.0001) in a time- and dose
      dependent manner. Necrosis was observed after prolonged exposure to elevated
      sulforaphane doses. Moreover, it markedly increased p53 and bax protein
      expression, and slightly affected bcl-2 expression. These findings indicate that
      sulforaphane but not the native GL GRA can exert both protective and toxic
      effects inhibiting leukemic cell growth. Sulforaphane therefore deserves study as
      a potential chemopreventive/chemotherapeutic antileukemic agent.

PMID- 11960908
TI  - Antitumor activity of Z-ajoene, a natural compound purified from garlic:
      antimitotic and microtubule-interaction properties.
AB  - Ajoene, a garlic stable oil-soluble sulfur rich compound was generally isolated
      as a mixture of two isomers [(E, Z)-4,5,9-trithiadodeca-1,6,11-triene-9-oxide].
      It has been described essentially as a potent inhibitor of platelet aggregation
      in vitro and in vivo. The antiproliferative effects of ajoene and experiments
      using a single isomer had received little attention. The present study aims at
      defining the antitumor activities of cis-Z-ajoene in vitro and in vivo.
      Antiproliferative activity of Z-ajoene was demonstrated against a panel of human
      tumor cell lines with IC(50) values varying from 5.2 mM to 26.1 mM and at a lower
      extent in normal marsupial kidney cells (PtK2). Meanwhile, Z-ajoene arrested HL60
      cells in G(2)/M phase of cell cycle in a dose and time-dependent way. In PtK2
      cells, exposure to 20 microM Z-ajoene for 6 h induced a complete disassembly of
      the microtubule network, that was associated with an increased number of cells
      blocked in early mitotic stages. An IC(50) for microtubule disassembly of 1
      microM was determined by a fully automated microplate-based multi-detection
      reader. In vitro, a reversible inhibition of the microtubule protein assembly was
      observed with an IC(50) of 25 microM Z-ajoene. In vivo, Z-ajoene inhibited tumor
      growth by 38% and 42% in mice grafted with sarcoma 180 and hepatocarcinoma 22,
      respectively. For the first time, Z-ajoene was shown to be a potent inhibitor of
      tumor cell growth both in vitro and in vivo. The microtubule cytoskeleton
      appeared to be one of the Z-ajoene targets, but the mechanisms by which Z-ajoene
      interacted with microtubule appeared different from those of other microtubule
      poisons such as those of the Vinca alkaloids family. The ability of Z-ajoene to
      preferentially suppress the growth of neoplastic cells could provide a new
      approach in tumor therapy.

PMID- 11960910
TI  - Induction of apoptosis in the lung but not in the liver of rats receiving intra
      tracheal instillations of chromium(VI).
AB  - Several studies have shown that hexavalent chromium [Cr(VI)] induces apoptosis in
      a variety of in vitro test systems. We instilled intra-tracheally either saline
      or sodium dichromate (0.25 mg/kg body weight), for three consecutive days, to
      Sprague-Dawley rats. TUNEL analyses showed a marked increase of the apoptotic
      index in both bronchial epithelium and lung parenchyma of Cr(VI)-treated rats,
      but no effect was detected in their liver. In parallel, the expression of 13 out
      of 18 apoptosis-related genes, evaluated by cDNA array analysis, was
      significantly enhanced in rat lung. The overexpressed genes included c-Jun N
      terminal kinases 1, 2 and 3, bcl-x, bcl-2-associated death promoter and bcl-2
      related ovarian killer protein, caspases 1, 3 and 6, DNase I precursor, DNA
      topoisomerases I and II alpha, and poly(ADP-ribose) polymerase. The enhancement
      of p53 expression in the lung was borderline to statistical significance.
      Expressions of bcl-2, bax-alpha, mdm2 and DNA topoisomerase IIB were not enhanced
      to a significant extent in lung. No induction of gene expression was observed in
      rat liver. RT-PCR analyses confirmed that Cr(VI) enhances the expression of c-Jun
      N-terminal kinase 1, caspase 6, and DNase I precursor but not that of bcl-2 in
      lung, while none of these genes was overexpressed in the liver of Cr(VI)-treated
      rats. The lack of stimulation of apoptosis in the liver parallels the failure of
      Cr(VI) to produce genotoxic damage, as we previously observed under identical
      experimental conditions. These negative findings may be ascribed to reduction of
      Cr(VI) to Cr(III) when traveling from the respiratory tract to the liver. On the
      other hand, induction of apoptosis in the respiratory tract parallels the
      occurrence of genotoxic effects and oxidative DNA damage produced by Cr(VI) in
      the same tissue. As previously shown in another laboratory, Cr(VI) did not induce
      lung tumors after 30 months of administration of the same daily dose. Therefore,
      apoptosis is likely to provide a protective mechanism at a post-genotoxic stage
      of Cr(VI) carcinogenesis.

PMID- 11960911
TI  - CYP2A6 gene deletion reduces oral cancer risk in betel quid chewers in Sri Lanka.
AB  - We investigated the relationship between inter-individual difference in CYP2A6
      genotype and susceptibility to oral cancer among habitual betel quid chewers in a
      Sri Lanka population. A total of 286 subjects showing oral malignant or
      premalignant lesions and 135 control subjects with no lesions were analyzed. The
      frequency of homozygotes for CYP2A6*4C mutation, a gene deletion type of
      polymorphism, was significantly lower in the case subjects than the controls. The
      odds ratio (OR) of the group homozygous for the deletion was significantly lower
      and calculated to be 0.14 (95% CI; 0.03-0.72). In the allelic base analysis,
      there was also a significant decrease in the OR of the deletion allele. Our data
      suggest that deficient CYP2A6 activity due to genetic polymorphism reduces oral
      cancer risk in betel quid chewers.

PMID- 11960912
TI  - The XPD variant alleles are associated with increased aromatic DNA adduct level
      and lung cancer risk.
AB  - The DNA repair protein xeroderma pigmentosum complementation group D (XPD) is
      involved in the nucleotide excision repair of DNA lesions induced by many tobacco
      and environmental carcinogens. In order to study the functional impact of the
      common polymorphisms in XPD exon 10 (G > A, Asp312Asn) and exon 23 (A > C,
      Lys751Gln), we have genotyped 185 Swedish lung cancer cases (97 smokers and 88
      never-smokers) and 162 matched population controls (83 smokers and 79 never
      smokers). Presence of one or two variant alleles was associated with increased
      risk for lung cancer among never-smokers only, in particular younger (<70 years)
      never-smokers [odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.1-6.5 for
      exon 10; OR = 3.2, 95% CI = 1.3-8.0 for exon 23, adjusted for age, gender and
      environmental tobacco smoke]. Aromatic DNA adduct level (AL) in peripheral
      lymphocytes was found to be similar between cases and controls, but significantly
      increased by current or recent smoking. Overall, there was a significant trend
      for increasing AL with increasing number of variant alleles in exon 10 (P = 0.02)
      or in exon 23 (P = 0.001). In addition, subjects with the combined exon 10 AA and
      exon 23 CC genotype showed a significantly higher AL compared with all those with
      any of the other genotypes (P = 0.02). We conclude that the XPD variant alleles
      may be associated with reduced repair of aromatic DNA adducts in general and
      increased lung cancer risk among never-smokers.

PMID- 11960913
TI  - Demonstration of UV-dimers in human skin DNA in situ 3 weeks after exposure.
AB  - Data on DNA repair rates of specific types of DNA lesions are very limited in
      humans in situ. Rate of repair of UV-induced DNA damage was followed in the skin
      of 17 volunteers up to 3 weeks of UV exposure, using a (32)P-postlabelling
      technique for the determination of specific photoproducts. The subjects of skin
      phototypes I and IV were exposed to 40 mJ/cm(2) of solar simulating radiation on
      buttock skin, and biopsies were taken at 0 h, 48 h and 3 weeks of exposure for
      the analysis of two cyclobutane pyrimidine dimers, TT=C and TT=T, and two 6-4
      photoproducts, TT-C and TT-T, as trinucleotides. Repair rates were heterogeneous
      for different photoproducts. T=T dimers were repaired slower than C=T dimers, and
      2.3-9.0% of the initial T=T damage remained unrepaired after 3 weeks, and was
      detectable in 16/17 subjects. The identity of the identified photoproducts was
      confirmed by a photochemical reversion assay. Damage level correlated with skin
      types, type I being more sensitive than type IV in an age-matched comparison.
      This is the first time the persistence of defined human DNA damage is
      demonstrated up to 3 weeks. Long-lasting DNA damage increases the likelihood of
      mutations.

PMID- 11960914
TI  - CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter
      individual variation in expression and relevance to nitrosamine metabolism.
AB  - Oesophageal cancer is one of the most common and lethal malignancies in the
      world. Despite many efforts, treatment is still ineffective for most cases; thus,
      the development of preventive strategies is crucial for decreasing the burden
      presented by this disease. Environmental factors, particularly nitrosamines, are
      thought to be involved in the genesis of oesophageal tumours, and knowledge about
      the expression of enzymes capable of activating pre-carcinogens in human
      oesophagus is very important for the development of preventive measures. We
      analysed the expression of CYP1A1, CYP1A2, CYP2A6/2A7, CYP2E1 and CYP3A4 mRNA in
      oesophageal mucosa of 50 patients by semi-quantitative RT-PCR. In five patients,
      who suffered from squamous cell carcinoma, we measured Nnitrosodimethylamine and
      N-nitrosodiethylamine metabolism in normal and tumorous tissue. CYP2A6/2A7 mRNA
      was expressed in 61% and CYP2E1 mRNA in 96% of the patients, but in the latter a
      lower degree of inter-individual variation was observed. These enzymes were
      expressed either in the distal or middle portions of the oesophagus of 90% of the
      patients. CYP1A1, CYP1A2 and CYP3A4 mRNA expression was not detected in any
      portion of the oesophagus. Oesophageal microsomes activated N
      nitrosodimethylamine with a low degree of inter-individual variation and
      microsomes prepared from the tumour of a patient who strongly expressed
      CYP2A6/2A7 mRNA activated N-nitrosodiethylamine. We conclude that the human
      oesophagus expresses CYP2A6/2A7 and CYP2E1 and can activate nitrosamines.
      Notably, the expression of these enzymes is preferentially localized to the most
      common sites where tumours arise.

PMID- 11960916
TI  - Enhanced spontaneous and aflatoxin-induced liver tumorigenesis in xeroderma
      pigmentosum group A gene-deficient mice.
AB  - Xeroderma pigmentosum (XP) is an autosomal recessive hereditary disease featuring
      defective nucleotide excision repair (NER). XP patients are highly sensitive to
      sunlight and develop skin cancer at an early age. While the fact that XP patients
      have a large increase in mortality from skin cancers has been extensively
      documented, the relation between XP and internal tumors has received little
      attention. We therefore analyzed development of spontaneous and aflatoxin B(1)
      (AFB(1))-induced liver tumors in XPA-deficient congenic mice, originally created
      by repeated back-crosses with inbred C3H/HeN mice. Spontaneous liver tumors were
      assessed at the age of 16 months in two separate experiments using F5 and F10
      lines. The incidence of and average number of spontaneous tumors per mouse were
      significantly higher in XPA-/- than in XPA+/+ and +/- mice. Similarly, F10 XPA-/-
      mice receiving i.p. injection of 0.6 or 1.5 mg/kg b.w. AFB(1) at 7 days of age
      demonstrated more liver tumors than their heterozygous or homozygous positive
      counterparts when examined at month 11. These results demonstrate that XPA
      deficient mice have increased susceptibility to both spontaneous liver tumor
      development and AFB(1)-induced hepatocarcinogenesis.

PMID- 11960915
TI  - Carcinogenic aristolochic acids upon activation by DT-diaphorase form adducts
      found in DNA of patients with Chinese herbs nephropathy.
AB  - Aristolochic acid (AA), a naturally occurring nephrotoxin and rodent carcinogen,
      has recently been associated with the development of urothelial cancer in humans.
      Understanding which enzymes are involved in AA activation and/or detoxication is
      important in the assessment of an individual susceptibility to this natural
      carcinogen. We examined the ability of enzymes of rat renal and hepatic cytosolic
      fractions to activate AA to metabolites forming DNA adducts by the nuclease P1
      enhanced version of the (32)P-postlabeling assay. Cytosolic fractions of both
      these organs generated AA-DNA adduct patterns reproducing those found in renal
      tissues from humans exposed to AA. 7-(Deoxyadenosin-N(6)-yl)aristolactam I, 7
      (deoxyguanosin-N(2)-yl)aristolactam I and 7-(deoxyadenosin-N(6)-yl)aristolactam
      II were identified as AA-DNA adducts formed from AAI and 7-(deoxyguanosin-N(2)
      yl)aristolactam II and 7-(deoxyadenosin-N(6)-yl)aristolactam II were generated
      from AAII by hepatic cytosol. Qualitatively the same AA-DNA adduct patterns were
      observed, although at lower levels, upon incubation of AAs with renal cytosol. To
      define the role of cytosolic reductases in the reductive activation of AA, we
      investigated the modulation of AA-DNA adduct formation by cofactors, specific
      inducers or selective inhibitors of the cytosolic reductases, DT-diaphorase,
      xanthine oxidase (XO) and aldehyde oxidase. The role of the enzymes in AA
      activation was also investigated by correlating the DT-diaphorase- and XO
      dependent catalytic activities in cytosolic sample with the levels of AA-DNA
      adducts formed by the same cytosolic sample. On the basis of these studies, we
      attribute most of the cytosolic activation of AA to DT-diaphorase, although a
      role of cytosolic XO cannot be ruled out. With purified DT-diaphorase, the
      participation of this enzyme in the formation of AA-DNA adducts was confirmed.
      The binding orientation of AAI in the active site of DT-diaphorase was predicted
      by computer modeling based on published X-ray structures. The results presented
      here are the first report demonstrating a reductive activation of carcinogenic
      AAs by DT-diaphorase.

PMID- 11960917
TI  - Gene expression profiling of initiated epidermal cells with benign or malignant
      tumor fates.
AB  - High-density oligonucleotide array technology was used to search for gene
      expression changes that may predict or cause sporadic tumorigenesis. To reduce
      variation among samples, a non-transformed mouse epidermal keratinocyte clone was
      compared with its carcinoma-producing or papilloma-producing 7,12
      dimethylbenz[a]anthracene-initiated cell derivative. The majority of the
      approximately 12 325 genes or expressed sequence tags (ESTs) analyzed remained
      unaltered reflective of the clonal nature of the model. Consistent gene
      expression changes among biological replicates included 69 in malignancy-prone
      initiated cells, 46 in papilloma-precursor initiated cells and an additional 45
      with changes in both initiated cell lineages. The changes covered a broad
      spectrum of cellular activities, implying that multiple pathways cooperate at the
      initiation of carcinogenesis. There was a tendency in the malignancy-prone cells
      for differences in proliferation and apoptosis-related genes. The benign lineage
      tended toward aberrant expression of genes involved in differentiation and
      epidermal barrier function. Several independently confirmed gene expression
      changes revealed plausible effectors to bypass an activated ras protein in
      proliferation pathways and to compromise the wild-type p53 and other apoptosis
      pathways at initiation of carcinogenesis. The differential expression patterns of
      the initiated cells are consistent with the hypothesis that changes in gene
      expression at initiation may cooperate with subsequent oncogenic changes to
      determine malignant fate. The cloned epidermal cell lineages allowed detection of
      putative early cancer genes in a model that is conducive to testing their direct
      role in epithelial multistep carcinogenesis in vitro and in vivo.

PMID- 11960918
TI  - Genetic status of cell cycle regulators in squamous cell carcinoma of the
      oesophagus: the CDKN2A (p16(INK4a) and p14(ARF) ) and p53 genes are major targets
      for inactivation.
AB  - We determined inactivation of the CDKN2A (p16(INK4a) and p14(ARF)) gene in 21
      cases of oesophageal squamous cell carcinoma (OSCC). The tumours were also
      analysed for mutations in exons 5-8 and allelic losses in the p53 gene. In
      addition, we screened the CDKN2B (p15 INK4b), CDKN2C (p18 INK4c), CDK4 and p53R2
      genes for mutations in the tumour tissues. Besides concomitant alterations in the
      CDKN2A and p53 loci in more than half of the cases, our results showed that in 18
      OSCC (86%) the CDKN2A (p16(INK4a) and p14(ARF) ) gene was affected through
      mutations, homozygous/hemizygous deletions and promoter hypermethylation. Eight
      out of 10 tumours with mutations or promoter hypermethylation specific to the
      CDKN2A/p16 INK4a gene showed loss of the wild-type allele. One tumour with a
      single base deletion in the N-terminus (codon 8) of the CDKN2A/p16(INK4a) gene
      carried a novel germ-line mutation or a rare polymorphism (Ile51Met) in exon 2 of
      the CDK4 gene. Promoter hypermethylation in the CDKN2A/p14 ARF gene was detected
      in 11 tumours. In the p53 gene 15 mutations were detected in 14 tumours. We
      detected an inverse relationship between CDKN2A/p16 INK4a inactivation and
      frequency of loss of heterozygosity at the p53 locus (OR 0.09, 95% CI 0.01-0.98;
      Fisher exact test, P-value approximately 0.03). Screening of nine exons of the
      p53R2 [Human Genome Organisation (HUGO) official name RRM2B] gene resulted in
      identification of a novel polymorphism in the 5' untranslated region, which was
      detected in four cases. Our results suggest that the CDKN2A (p16(INK4a) and
      p14(ARF) ) and p53 genes involved in the two cell cycle pathways are major and
      independent targets of inactivation in OSCC.

PMID- 11960919
TI  - Overexpression of a dominant-negative ornithine decarboxylase in mouse skin:
      effect on enzyme activity and papilloma formation.
AB  - A transgenic mouse line expressing a truncated form of the ornithine
      decarboxylase (ODC) dominant-negative mutant K69A/C360A under the control of the
      keratin 6 promoter has been established (K6/ODCdn mice). These mice were
      backcrossed onto both the DBA/2J and C57BL/6J backgrounds for subsequent
      tumorigenesis experiments utilizing an initiation/promotion protocol. In short
      term experiments, expression of the ODCdn protein product was induced in the
      epidermis within 24 h after application of the tumor promoter tetradecanoyl
      phorbol acetate (TPA) to the skin, and ODC activity in the epidermis of K6/ODCdn
      mice was reduced by at least 75% compared with littermate controls. However, in
      tumorigenesis experiments utilizing a variety of initiator (7,12
      dimethylbenz[a]anthracene; DMBA) and promoter (TPA) concentrations, K6/ODCdn mice
      formed at least as many tumors as their littermate controls regardless of
      background strain. In experiments utilizing chrysarobin, a tumor promoter with a
      different mechanism of action than TPA, again there was no significant difference
      in tumor formation between K6/ODCdn mice and littermate controls. Similarly, when
      K6/ODCdn mice were crossed with K5/ODC mice, a transgenic line described
      previously which forms tumors without application of a promoting agent, double
      transgenic mice formed as many tumors as mice expressing the K5/ODC transgene
      alone. Analysis of epidermis following multiple TPA applications revealed a
      dramatic spike in ODC activity in both K6/ODCdn mice and non-transgenic mice
      after six applications, and western blot analysis suggested a stabilization of
      endogenous wild-type ODC in K6/ODCdn transgenic mice. ODC activity, endogenous
      protein and polyamines were also elevated in tumors from K6/ODCdn mice. The
      accumulation of endogenous ODC protein is most probably the result of competition
      from the transgene-derived ODCdn protein for binding of antizyme, which is known
      to regulate ODC activity by stimulating degradation of the ODC protein.

PMID- 11960920
TI  - Association of CYP2C9 genotypes leading to high enzyme activity and colorectal
      cancer risk.

PMID- 11960923
TI  - Multiple sclerosis and thermoregulatory dysfunction.

PMID- 11960924
TI  - Modeling the energetics of 100-m running by using speed curves of world
      champions.
AB  - The present study aims to assess energy demand and supply in 100-m sprint
      running. A mathematical model was used in which supply has two components,
      aerobic and anaerobic, and demand has three components, energy required to move
      forward (C), energy required to overcome air resistance (Caero), and energy
      required to change kinetic energy (Ckin). Supply and demand were equated by using
      assumed efficiency of converting metabolic to external work. The mathematical
      model uses instantaneous velocities registered by the 1997 International
      Association of Athletics Federations world champions at 100 m in men and women.
      Supply and demand components obtained in the male champion were (in J/kg) aerobic
      30 (5%), anaerobic 607 (95%), C 400 (63%), Caero 83 (13%), Ckin 154 (24%).
      Comparatively, a model that uses the average velocity of the male and female 100
      m champions overestimates Ckin by 37 and 44%, respectively, and underestimates
      Caero by 14%. We argued that such a model is not appropriate because Ckin and
      Caero are nonlinear functions of velocity. Neither height nor body mass seems to
      have any advantage in the energetics of sprint running.

PMID- 11960925
TI  - Raised plasma G-CSF and IL-6 after exercise may play a role in neutrophil
      mobilization into the circulation.
AB  - We examined the hypothesis that the short, intensive exercise-induced increase in
      circulating neutrophil counts is affected by the interaction between the
      endocrine and immune systems. Twelve male winter-sports athletes underwent a
      maximal exercise test on a treadmill. Blood samples were collected before,
      immediately after (Post), and 1 h (Post 1 h) and 2 h (Post 2 h) after the
      exercise. The neutrophil counts increased significantly at Post 1 h (P < 0.05)
      and remained significantly high even at Post 2 h (P < 0.05), showing a leftward
      shift. Plasma granulocyte colony-stimulating factor (G-CSF) increased at Post (P
      < 0.05), and interleukin-6 (IL-6) increased at Post 1 h (P < 0.05). Plasma G-CSF
      at Post significantly correlated with the numbers of both neutrophils and stab
      cells at Post 1 h (P < 0.05). Plasma IL-6 at Post 1 h levels also correlated
      significantly with the number of neutrophils at Post 2 h (P < 0.05). The increase
      in the levels of plasma G-CSF and IL-6 after intensive exercise may play a role
      in the mobilization of neutrophils into the circulatory system.

PMID- 11960926
TI  - Increases in maximal accumulated oxygen deficit after high-intensity interval
      training are not gender dependent.
AB  - Gender differences in maximal accumulated oxygen deficit (MAOD) were examined
      before and after 4 and 8 wk of high-intensity interval training. Untrained men (n
      = 7) and women (n = 7) cycled at 120% of pretraining peak oxygen uptake (VO2
      peak) to exhaustion (MAOD test) pre-, mid-, and posttraining. A posttraining
      timed test was also completed at the MAOD test power output, but this test was
      stopped at the time to exhaustion achieved during the pretraining MAOD test. The
      14.3 +/- 5.2% increase in MAOD observed in men after 4 wk of training was not
      different from the 14.0 +/- 3.0% increase seen in women (P > 0.05). MAOD
      increased by a further 6.6 +/- 1.9% in men, and this change was not different
      from the additional 5.1 +/- 2.3% increase observed in women after the final 4 wk
      of training. VO2 peak measured during incremental cycling increased significantly
      (P < 0.01) in male but not in female subjects after 8 wk of training. Moreover,
      the accumulated oxygen (AO2) uptake was higher in men during the posttraining
      timed test compared with the pretraining MAOD test (P < 0.01). In contrast, the
      AO2 uptake was unchanged from pre- to posttraining in female subjects. The
      increase in MAOD with training was not different between men and women,
      suggesting an enhanced ability to produce ATP anaerobically in both groups.
      However, the increase in VO2 peak and AO2 uptake obtained in male subjects after
      training indicates improved oxidative metabolism in men but not in women. We
      conclude that there are basic gender differences that may predispose men and
      women to specific metabolic adaptations after a period of intense interval
      training.

PMID- 11960927
TI  - Nonlinearity of respiratory mechanics during bronchoconstriction in mice with
      airway inflammation.
AB  - Respiratory system resistance (R) and elastance (E) are commonly estimated by
      fitting the linear equation of motion P = EV + RV + P0 (Eq. 1) to measurements of
      respiratory pressure (P), lung volume (V), and flow (V). However, the respiratory
      system is unlikely to behave linearly under many circumstances. We determined the
      importance of respiratory system nonlinearities in two groups of mechanically
      ventilated Balb/c mice [controls and mice with allergically inflamed airways
      (ova/ova)], by assessing the impact of the addition of nonlinear terms (E2V2 and
      R2V(V)) on the goodness of model fit seen with Eq. 1. Significant improvement in
      fit (51.85 +/- 4.19%) was only seen in the ova/ova mice during
      bronchoconstriction when the E2V2 alone was added. An improvement was also
      observed with addition of the E2V2 term in mice with both low and high lung
      volumes ventilated at baseline, suggesting a volume-dependent nonlinearity of E.
      We speculate that airway closure in the constricted ova/ova mice accentuated the
      volume-dependent nonlinearity by decreasing lung volume and overdistending the
      remaining lung.

PMID- 11960929
TI  - Correlation properties of tidal volume and end-tidal O2 and CO2 concentrations in
      healthy infants.
AB  - We investigated whether breath-to-breath fluctuations in tidal volume (VT) and
      end-tidal O2 and CO2 exhibit long-range correlations and whether parameters
      describing the correlations can be used as noninvasive descriptors of control of
      breathing. We measured VT and end-tidal O2 and CO2 over n = 352 +/- 104 breaths
      in 26 term, healthy, unsedated infants (mean age +/- SD: 36 +/- 6 days) and
      calculated the detrended fluctuation function [F(n)]. The F(n) of the breath-to
      breath time series of VT, O2, and CO2 revealed a linear increase with a breath
      number on log-log plots with a slope that was significantly different from 0.5
      (random) and thus consistent with scale-invariant behavior. Long-range
      correlations were stronger for O2 than for VT and CO2. The F(n) of many
      individual signals exhibited a crossover behavior indicating that control
      mechanisms regulating fluctuations of VT, O2, and CO2 may be different on
      different time scales. Thus breathing has a memory up to at least 400 breaths
      that can be characterized by the simple indicator alpha.

PMID- 11960928
TI  - Diaphragm arterioles are less responsive to alpha1- adrenergic constriction than
      gastrocnemius arterioles.
AB  - The sympathetic nervous system has greater influence on vascular resistance in
      low-oxidative, fast-twitch skeletal muscle than in high-oxidative skeletal muscle
      (17). The purpose of this study was to test the hypothesis that arterioles
      isolated from low-oxidative, fast-twitch skeletal muscle [the white portion of
      gastrocnemius (WG)] possess greater responsiveness to adrenergic constriction
      than arterioles isolated from high-oxidative skeletal muscle [red portion of the
      gastrocnemius muscle (RG) and diaphragm (Dia)]. Second-order arterioles (2As)
      were isolated from WG, RG, and Dia of rats and reactivity examined in vitro.
      Results reveal that Dia 2As constrict less to norepinephrine (NE) (10(-9) to 10 (
      4) M) than 2As from RG and WG, which exhibited similar NE-induced constrictions.
      This difference was not endothelium dependent, because responses of denuded 2As
      were similar to those of intact arterioles. The blunted NE-induced constrictor
      response of Dia 2As appears to be the result of differences in alpha1-receptor
      effects because 1) arterioles from Dia also responded less to selective alpha1
      receptor stimulation with phenylephrine than RG and WG arterioles; 2) arterioles
      from Dia, RG, and WG dilated similarly to isoproterenol (10(-9) to 10(-4) M) and
      did not respond to selective alpha2-receptor stimulation with UK-14304; and 3)
      endothelin-1 produced similar constriction in 2As from Dia, RG, and WG. We
      conclude that differences in oxidative capacity and/or fiber type composition of
      muscle tissue do not explain different NE responsiveness of Dia 2As compared with
      2As from gastrocnemius muscle. Differences in alpha1-adrenergic constrictor
      responsiveness among arterioles in skeletal muscle may contribute to nonuniform
      muscle blood flow responses observed during exercise and serve to maintain blood
      flow to Dia during exercise-induced increases in sympathetic nerve activity.

PMID- 11960930
TI  - Interactive effects of mental and physical stress on cardiovascular control.
AB  - Physiological responses to mental tasks and physical exercise were studied
      independently and combined. We hypothesized that combined mental and physical
      stresses produce a synergistic interaction. We studied cardiovascular responses
      to 5 min of static handgrip, mental arithmetic, and the combined stimuli in
      random order in 12 healthy subjects. Muscle sympathetic nerve activity (SNA) and
      mean arterial blood pressure (MAP) responses to handgrip and the combined stimuli
      exceeded responses to mental arithmetic, yet no significant difference existed
      between responses to handgrip and the combined stimuli. Peak changes in SNA (in
      %) were greatest during handgrip (188 +/- 41), followed by the combined stimuli
      (166 +/- 31) and mental arithmetic (51 +/- 9). Peak changes in MAP (in mmHg) were
      also greatest during handgrip (26 +/- 4), followed by the combined stimuli (23 +/
      3) and then mental arithmetic (8 +/- 2). Peak changes in heart rate (in
      beats/min) followed the same trend: handgrip (15 +/- 2), combined (13 +/- 2), and
      mental arithmetic (10 +/- 2). Mental stimulation did not synergistically interact
      with or add to the responses elicited by handgrip exercise; in fact, a trend
      existed for math during handgrip to reduce responses relative to handgrip alone.

PMID- 11960931
TI  - Relaxation of guinea pig trachealis during electrical field stimulation increases
      with age.
AB  - Our laboratory has previously shown that maturation of airway smooth muscle (ASM)
      contractility may play a role in the airway hyperresponsiveness displayed by
      juveniles of many species, including humans (Chitano P, Wang J, Cox CM, Stephens
      NL, and Murphy TM. J Appl Physiol 88: 1338-1345, 2000). ASM relaxation, which
      could also contribute to airway hyperresponsiveness, has neither been described
      nor quantified during maturation. Therefore, we studied ASM relaxation during and
      after electrical field stimulation (EFS) in tracheal strips from 1-wk-old, 3-wk
      old, and 3-mo-old guinea pigs. Strips were stimulated (60 Hz, 18 V) at their
      optimal length for 15, 20, and 25 s, with and without the cyclooxygenase
      inhibitor indomethacin. To evaluate the role of the epithelium, deepithelialized
      strips from adult animals were also studied. New indexes were developed to
      quantify relaxation during EFS. We measured the time course of tension relaxation
      and its maximum rate (RTR) during the EFS, as well as the residual tension at the
      end of the EFS (TCT(end)). After EFS, we measured the maximum RTR and the time
      needed to reduce to half the TCT(end). Relaxation during the EFS significantly
      increased with age. Indomethacin reduced this age difference by increasing
      relaxation in strips from younger animals. By contrast, removal of the epithelium
      in adult strips decreased relaxation. Relaxation after EFS decreased with age and
      was not affected by indomethacin. In adult strips, it was further reduced by
      epithelium removal. Our results show that during EFS 1) airway smooth muscle
      relaxation increases with age, 2) cyclooxygenase metabolites oppose relaxation in
      younger animals, and 3) epithelium removal inhibits relaxation. We suggest that a
      reduced ASM relaxing ability during stimulation may be involved in juvenile
      airway hyperresponsiveness.

PMID- 11960933
TI  - Mechanical ventilation results in progressive contractile dysfunction in the
      diaphragm.
AB  - These experiments tested the hypothesis that a relatively short duration of
      controlled mechanical ventilation (MV) will impair diaphragmatic maximal specific
      force generation (specific P(o)) and that this force deficit will be exacerbated
      with increased time on the ventilator. To test this postulate, adult Sprague
      Dawley rats were randomly divided into one of six experimental groups: 1) control
      (n = 12); 2) 12 h of MV (n = 4); 3) 18 h of MV (n = 4); 4) 18 h of anesthesia and
      spontaneous breathing (n = 4); 5) 24 h of MV (n = 7); and 6) 24 h of anesthesia
      and spontaneous breathing (n = 4). MV animals were anesthetized, tracheostomized,
      and ventilated with room air. Animals in the control group were acutely
      anesthetized but were not exposed to MV. Animals in two spontaneous breathing
      groups were anesthetized and breathed spontaneously for either 18 or 24 h. No
      differences (P > 0.05) existed in diaphragmatic specific P(o) between control and
      the two spontaneous breathing groups. In contrast, compared with control, all
      durations of MV resulted in a reduction (P < 0.05) in diaphragmatic specific
      tension at stimulation frequencies ranging from 15 to 160 Hz. Furthermore, the MV
      induced decrease in diaphragmatic specific P(o) was time dependent, with specific
      P(o) being approximately 18 and approximately 46% lower (P < 0.05) in animals
      mechanically ventilated for 12 and 24 h, respectively. These data support the
      hypothesis that relatively short-term MV impairs diaphragmatic contractile
      function and that the magnitude of MV-induced force deficit increases with time
      on the ventilator.

PMID- 11960932
TI  - Distal projection of insufflated gas during tracheal gas insufflation.
AB  - Tracheal gas insufflation (TGI) flushes expired gas from the ventilator circuitry
      and central airways, augmenting CO2 clearance. Whereas a significant portion of
      this washout effect may occur distal to the injection orifice, the penetration
      and mixing behavior of TGI gas has not been studied experimentally. We examined
      the behavior of 100% oxygen TGI injected at set flow rates of 1-20 l/min into a
      simulated trachea consisting of a smooth-walled, 14-mm-diameter tube. Models
      incorporating a separate coaxial TGI injector, a rough-walled trachea, and a
      bifurcated trachea were also studied. One-hundred percent nitrogen, representing
      expiratory flow, passed in the direction opposite to TGI at set flow rates of 1
      25 l/min. Oxygen concentration within the "trachea" was mapped as a function of
      axial and radial position. Three consistent findings were observed: 1) mixing of
      expiratory and TGI gases occurred close to the TGI orifice; 2) the oxygenated
      domain extended several centimeters beyond the endotracheal tube, even at high
      expiratory flows, but had a defined distal limit; and 3) more distally from the
      site of gas injection, the TGI gas tended to propagate along the tracheal wall,
      rather than as a central projection. We conclude that forward-directed TGI
      penetrates a substantial distance into the central airways, extending the
      compartment susceptible to CO2 washout.

PMID- 11960934
TI  - Chronic hypoxia increases MCA contractile response to U-46619 by reducing NO
      production and/or activity.
AB  - Chronic hypoxia alters contractile sensitivity of isolated arteries to alpha
      adrenergic stimulation and other agonists. However, most studies have been
      performed in thoracic aortas or other large vessels making little contribution to
      vascular resistance in their respective circulations. To determine the effect of
      chronic hypoxia on the vasoconstrictor response in a small, resistance-sized
      vessel, we studied second and third generation middle cerebral arteries (MCA;
      approximately 75-microm internal diameter before mounting). MCA were isolated
      from normoxic (inspired oxygen = 125 Torr) and hypoxic (8 wk at 3,960 m; inspired
      oxygen = 90 Torr) guinea pigs, and their vasoconstrictor responses were
      determined to the thromboxane mimetic U-46619 by using dual-pipette video
      microscopy. Arteries from hypoxic animals had greater contractile sensitivity to
      U-46619 compared with those of the normoxic animals (-log EC50 = 7.86 +/- 0.11
      vs. 7.62 +/- 0.06, respectively, P < 0.05). Addition of the nitric oxide (NO)
      inhibitor nitro-L-arginine (200 microM) to the vessel bath eliminated the
      differences in contractile sensitivity between the MCA from the normoxic and
      chronically hypoxic groups. Supplementation with L-arginine in the drinking water
      sufficient to raise plasma L-arginine levels 41% reduced MCA contractile
      sensitivity to U-46619 in the normoxic group (-log EC50 = 7.22 +/- 0.31, P < 0.05
      compared with the nonsupplemented normoxic group) but not in the chronically
      hypoxic group. These results show that chronic hypoxia increases the sensitivity
      of the MCA to the vasoconstrictor U-46619, likely because of a reduction in NO
      production and/or activity.

PMID- 11960935
TI  - Changes in force-velocity properties of trachealis due to oscillatory strains.
AB  - The physically dynamic environment of the lung constantly modulates the
      mechanical properties of airway smooth muscle. In vitro experiments have shown
      that contractility of the muscle is compromised by oscillatory strains, perhaps
      through disruption of cross-bridge interaction and organization of the
      contractile filaments. To understand the mechanism by which oscillation affects
      contractility, functional changes of the muscle in terms of force-velocity
      relationship were assessed before and after imposition of length oscillation in
      both relaxed and activated states. The oscillation protocol was designed to
      reduce isometric force by 15-20%, followed by measurement of force-velocity
      properties. Maximal velocity and power changed by +8 and -14%, respectively,
      after oscillation applied in the relaxed state and changed by -15 and -25%,
      respectively, after oscillation applied during contraction. A simple model of
      reduced activation could not account for the results; neither could the results
      be explained satisfactorily by the current cross-bridge theory of contraction.
      The results, however, could be explained if the possibility of reorganization of
      the contractile filaments due to oscillatory strains was considered.

PMID- 11960936
TI  - Muscle inflammatory cells after passive stretches, isometric contractions, and
      lengthening contractions.
AB  - We tested the hypotheses that lengthening contractions, isometric contractions,
      and passive stretches increase muscle inflammatory cells (neutrophils and
      macrophages) and that prior conditioning with lengthening contractions, isometric
      contractions, or passive stretches reduces neutrophils and macrophages after
      subsequent lengthening contractions. Extensor digitorum longus muscles in
      anesthetized mice were subjected in situ to lengthening contractions, isometric
      contractions, or passive stretches. Six hours or 3 days after a protocol of
      contractions or passive stretches, neutrophils and macrophages were quantified in
      muscle cross sections. Three days after isometric contractions or passive
      stretches, neutrophils were elevated (P < 0.05) 3.7- and 5.5-fold, respectively,
      relative to controls. Both macrophages and neutrophils were increased 51.2- and
      7.9-fold, respectively, after lengthening contractions. Prior lengthening
      contractions, isometric contractions, or passive stretches reduced inflammatory
      cells after lengthening contractions performed 2 wk later. The major finding of
      this study was that passive stretches and isometric contractions elevated
      neutrophils without causing overt signs of injury. Because both passive stretches
      and isometric contractions elevated neutrophils and afforded some protection from
      contraction-induced muscle injury, neutrophils and/or the related inflammatory
      events may contribute to the induction of a protective mechanism.

PMID- 11960937
TI  - Early onset of pulmonary gas exchange disturbance during progressive exercise in
      healthy active men.
AB  - Some recent studies of competitive athletes have shown exercise-induced hypoxemia
      to begin in submaximal exercise. We examined the role of ventilatory factors in
      the submaximal exercise gas exchange disturbance (GED) of healthy men involved in
      regular work-related exercise but not in competitive activities. From the 38
      national mountain rescue workers evaluated (36 +/- 1 yr), 14 were classified as
      GED and were compared with 14 subjects matched for age, height, weight, and
      maximal oxygen uptake (VO2 max; 3.61 +/- 0.12 l/min) and showing a normal
      response (N). Mean arterial PO2 was already lower than N (P = 0.05) at 40% VO2
      max and continued to fall until VO2 max (GED: 80.2 +/- 1.6 vs. N: 91.7 +/- 1.3
      Torr). A parallel upward shift in the alveolar-arterial oxygen difference vs.
      %VO2 max relationship was observed in GED compared with N from the onset
      throughout the incremental protocol. At submaximal intensities, ideal alveolar
      PO2, tidal volume, respiratory frequency, and dead space-to-tidal volume ratio
      were identical between groups. As per the higher arterial PCO2 of GED at VO2 max,
      subjects with an exaggerated submaximal alveolar-arterial oxygen difference also
      showed a relative maximal hypoventilation. Results thus suggest the existence of
      a common denominator that contributes to the GED of submaximal exercise and
      affects the maximal ventilatory response.

PMID- 11960938
TI  - Variability of ground reaction forces during treadmill walking.
AB  - The purpose of this study was to investigate whether or not the neuromuscular
      locomotor system is optimized at a unique speed by examining the variability of
      the ground reaction force (GRF) pattern during walking in relation to different
      constant speeds. Ten healthy male subjects were required to walk on a treadmill
      at 3.0, 4.0, 5.0, 6.0, 7.0, and 8.0 km/h. Three components [vertical (F(z)),
      anteroposterior (F(y)), and mediolateral (F(x)) force] of the GRF were
      independently measured for approximately 35 steps consecutively for each leg. To
      quantify the GRF pattern, five indexes (first and second peaks of F(z), first and
      second peaks of F(y), and F(x) peak) were defined. Coefficients of variation were
      calculated for these five indexes to evaluate the GRF variability for each
      walking speed. It became clear for first and second peaks of F(z) and F(x) peak
      that index variabilities increased in relation to increments in walking speed,
      whereas there was a speed (5.5-5.8 km/h) at which variability was minimum for
      first and second peaks of F(y), which were related to forward propulsion of the
      body. These results suggest that there is "an optimum speed" for the
      neuromuscular locomotor system but only for the propulsion control mechanism.

PMID- 11960939
TI  - Membrane leakage and increased content of Na+ -K+ pumps and Ca2+ in human muscle
      after a 100-km run.
AB  - During prolonged exercise, changes in the ionic milieu in and surrounding the
      muscle fibers may lead to fatigue or damage of the muscle and thereby impair
      performance. In 10 male subjects, we investigated the effects of 100 km running
      on muscle and plasma electrolyte contents, muscle Na+ -K+ pump content, and
      plasma concentrations of creatine kinase (CK) and lactate dehydrogenase (LDH).
      After completion of a 100-km run, significant increases were found in plasma K+
      (from 4.0 +/- 0.1 to 5.5 +/- 0.2 mM, P < 0.001), muscle Na+ -K+ pump content
      (from 334 +/- 11 to 378 +/- 17 pmol/g, P < 0.05), and total muscle Ca2+ content
      (from 0.84 +/- 0.03 to 1.02 +/- 0.04 micromol/g, P < 0.001). There was also a
      large increase in the plasma levels of the muscle-specific enzymes CK and LDH,
      which reached peak values at the end of the run and lasted several days after the
      run, indicating that a significant degree of muscle membrane leakage was present.
      The simultaneous occurrence of raised cellular Ca2+ content and muscle membrane
      leakage supports the theory that Ca2+ plays a role in the initiation of
      degenerative processes in muscles after severe exercise.

PMID- 11960940
TI  - Modulation of phrenic motoneuron excitability by ATP: consequences for
      respiratory-related output in vitro.
AB  - On the basis of the high level of P2X receptor expression found in phrenic
      motoneurons (MN) in rats (Kanjhan et al., J Comp Neurol 407: 11-32, 1999) and
      potentiation of hypoglossal MN inspiratory activity by ATP (Funk et al., J
      Neurosci 17: 6325-6337, 1997), we tested the hypothesis that ATP receptor
      activation also modulates phrenic MN activity. This question was examined in
      rhythmically active brain stem-spinal cord preparations from neonatal rats by
      monitoring effects of ATP on the activity of spinal C4 nerve roots and phrenic
      MNs. ATP produced a rapid-onset, dose-dependent, suramin- and pyridoxal-phosphate
      6-azophenyl-2',4'-disulphonic acid 4-sodium-sensitive increase in C4 root tonic
      discharge and a 22 +/- 7% potentiation of inspiratory burst amplitude. This was
      followed by a slower, 10 +/- 5% reduction in burst amplitude. ATPgammaS, the
      hydrolysis-resistant analog, evoked only the excitatory response. ATP induced
      inward currents (57 +/- 39 pA) and increased repetitive firing of phrenic MNs.
      These data, combined with persistence of ATP currents in TTX and immunolabeling
      for P2X2 receptors in Fluoro-Gold-labeled C4 MNs, implicate postsynaptic P2
      receptors in the excitation. Inspiratory synaptic currents, however, were
      inhibited by ATP. This inhibition differed from that seen in root recordings; it
      did not follow an excitation, had a faster onset, and was induced by ATPgammaS.
      Thus ATP inhibited activity through at least two mechanisms: 1) a rapid P2
      receptor-mediated inhibition and 2) a delayed P1 receptor-mediated inhibition
      associated with hydrolysis of ATP to adenosine. The complex effects of ATP on
      phrenic MNs highlight the importance of ATP as a modulator of central motor
      outflows.

PMID- 11960941
TI  - Prolonged hypobaric hypoxemia attenuates vasopressin secretion and renal response
      to osmostimulation in men.
AB  - Effects of hypobaric hypoxemia on endocrine and renal parameters of body fluid
      homeostasis were investigated in eight normal men during a sojourn of 8 days at
      an altitude of 4,559 m. Endocrine and renal responses to an osmotic stimulus (5%
      hypertonic saline, 3.6 ml/kg over 1 h) were investigated at sea level and on day
      6 at altitude. Several days of hypobaric hypoxemia reduced body weight (-2.1 +/-
      0.4 kg), increased plasma osmolality (+5.3 +/- 1.4 mosmol/kgH(2)O), elevated
      blood pressure (+12 +/- 1 mmHg), reduced creatinine clearance (122 +/- 6 to 96 +/
      10 ml/min), inhibited the renin system (19.5 +/- 2.0 to 10.9 +/- 0.9 mU/l) and
      plasma vasopressin (1.14 +/- 0.16 to 0.38 +/- 0.06 pg/ml), and doubled
      circulating levels of norepinephrine (103 +/- 16 to 191 +/- 35 pg/ml) and
      endothelin-1 (3.0 +/- 0.2 to 6.3 +/- 0.6 pg/ml), whereas urodilatin excretion
      rate decreased from day 2 (all changes P < 0.05 compared with sea level). Plasma
      arginine vasopressin response and the antidiuretic response to hypertonic saline
      loading were unchanged, but the natriuretic response was attenuated. In
      conclusion, chronic hypobaric hypoxemia 1) elevates the set point of plasma
      osmolality-to-plasma vasopressin relationship, possibly because of concurrent
      hypertension, thereby causing hypovolemia and hyperosmolality, and 2) blunts the
      natriuretic response to hypertonic volume expansion, possibly because of elevated
      circulating levels of norepinephrine and endothelin, reduced urodilatin
      synthesis, or attenuated inhibition of the renin system.

PMID- 11960942
TI  - Effects of spontaneous swallows on breathing in awake goats.
AB  - The effects of spontaneous swallows on breathing before, during, and after
      solitary swallows were investigated in 13 awake goats. Inspiratory (TI) and
      expiratory (TE) time and respiratory output were determined from inspiratory
      airflow [tidal volume (VT)] and peak diaphragmatic activity (Dia(peak)). The
      onset time for 1,128 swallows was determined from pharyngeal muscle electrical
      activity. During inspiration, the later the swallowing onset, the greater
      increase in TI and VT, whereas there was no significant effect on TE and
      Dia(peak). Swallows in early expiration increased the preceding TI and reduced
      TE, whereas later in expiration swallows increased TE. After expiratory swallows,
      TI and VT were reduced whereas minimal changes in Dia(peak) were observed. Phase
      response analysis revealed a within-breath, phase-dependent effect of swallowing
      on breathing, resulting in a resetting of the respiratory oscillator. However,
      the shift in timing in the breaths after a swallow was not parallel, further
      demonstrating a respiratory phase-dependent effect on breathing. We conclude
      that, in the awake state, within- and multiple-breath effects on respiratory
      timing and output are induced and/or required in the coordination of breathing
      and swallowing.

PMID- 11960943
TI  - Effects of microgravity on myogenic factor expressions during postnatal
      development of rat skeletal muscle.
AB  - To clarify the role of gravity in the postnatal development of skeletal muscle,
      we exposed neonatal rats at 7 days of age to microgravity. After 16 days of
      spaceflight, tibialis anterior, plantaris, medial gastrocnemius, and soleus
      muscles were removed from the hindlimb musculature and examined for the
      expression of MyoD-family transcription factors such as MyoD, myogenin, and MRF4.
      For this purpose, we established a unique semiquantitative method, based on RT
      PCR, using specific primers tagged with infrared fluorescence. The relative
      expression of MyoD in the tibialis anterior and plantaris muscles and that of
      myogenin in the plantaris and soleus muscles were significantly reduced (P <
      0.001) in the flight animals. In contrast, MRF4 expression was not changed in any
      muscle. These results suggest that MyoD and myogenin, but not MRF4, are sensitive
      to gravity-related stimuli in some skeletal muscles during postnatal development.

PMID- 11960944
TI  - Determinants of exercise performance in normal men with externally imposed
      expiratory flow limitation.
AB  - To understand how externally applied expiratory flow limitation (EFL) leads to
      impaired exercise performance and dyspnea, we studied six healthy males during
      control incremental exercise to exhaustion (C) and with EFL at approximately 1.
      We measured volume at the mouth (Vm), esophageal, gastric and transdiaphragmatic
      (Pdi) pressures, maximal exercise power (W(max)) and the difference (Delta) in
      Borg scale ratings of breathlessness between C and EFL exercise. Optoelectronic
      plethysmography measured chest wall and lung volume (VL). From Campbell diagrams,
      we measured alveolar (PA) and expiratory muscle (Pmus) pressures, and from Pdi
      and abdominal motion, an index of diaphragmatic power (W(di)). Four subjects
      hyperinflated and two did not. EFL limited performance equally to 65% W(max) with
      Borg = 9-10 in both. At EFL W(max), inspiratory time (TI) was 0.66s +/- 0.08,
      expiratory time (TE) 2.12 +/- 0.26 s, Pmus approximately 40 cmH2O and DeltaVL
      DeltaVm = 488.7 +/- 74.1 ml. From PA and VL, we calculated compressed gas volume
      (VC) = 163.0 +/- 4.6 ml. The difference, DeltaVL-DeltaVm-VC (estimated blood
      volume shift) was 326 ml +/- 66 or 7.2 ml/cmH2O PA. The high Pmus and long TE
      mimicked a Valsalva maneuver from which the short TI did not allow recovery.
      Multiple stepwise linear regression revealed that the difference between C and
      EFL Pmus accounted for 70.3% of the variance in DeltaBorg. DeltaW(di) added
      12.5%. We conclude that high expiratory pressures cause severe dyspnea and the
      possibility of adverse circulatory events, both of which would impair exercise
      performance.

PMID- 11960945
TI  - Respiratory muscle dynamics and control during exercise with externally imposed
      expiratory flow limitation.
AB  - To determine how decreasing velocity of shortening (U) of expiratory muscles
      affects breathing during exercise, six normal men performed incremental exercise
      with externally imposed expiratory flow limitation (EFLe) at approximately 1 l/s.
      We measured volumes of chest wall, lung- and diaphragm-apposed rib cage (Vrc,p
      and Vrc,a, respectively), and abdomen (Vab) by optoelectronic plethysmography;
      esophageal, gastric, and transdiaphragmatic pressures (Pdi); and end-tidal CO2
      concentration. From these, we calculated velocity of shortening and power (W) of
      diaphragm, rib cage, and abdominal muscles (di, rcm, ab, respectively). EFLe
      forced a decrease in Uab, which increased Pab and which lasted well into
      inspiration. This imposed a load, overcome by preinspiratory diaphragm
      contraction. Udi and inspiratory Urcm increased, reducing their ability to
      generate pressure. Pdi, Prcm, and Wab increased, indicating an increased central
      drive to all muscle groups secondary to hypercapnia, which developed in all
      subjects. These results suggest a vicious cycle in which EFLe decreases Uab,
      increasing Pab and exacerbating the hypercapnia, which increases central drive
      increasing Pab even more, leading to further CO2 retention, and so forth.

PMID- 11960946
TI  - Blood flow distribution within the airway wall.
AB  - Altered perfusion of the bronchial mucosal plexus relative to the adventitial
      plexus may contribute to geometric changes in the airway wall and lumen. We
      studied bronchial perfusion distribution in sheep by using fluorescent
      microspheres at baseline and during intrabronchial artery challenge with
      methacholine chloride (MCh; n = 7). Additionally, we measured airway resistance
      (Raw) during MCh with control or increased perfusion (n = 9). Raw with MCh was
      significantly greater for high than control flow. Microspheres in histological
      sections lodged predominantly in the mucosa (60%), and this was not altered by
      MCh. However, more microspheres lodged in airways >1-mm in diameter during MCh
      and increased perfusion than MCh and control flow. In airways < or =1 mm in
      diameter, fewer microspheres lodged during control than increased flow. If the
      number of microspheres represents regional agonist access to airway smooth
      muscle, then the differences observed in Raw can be explained by the distribution
      of agonist. During challenge, there was greater MCh delivery to larger airways
      during increased flow and less delivery to smaller airways during control flow.
      The results demonstrate the effects of axial perfusion distribution on Raw.

PMID- 11960947
TI  - Influence of vitamin C supplementation on oxidative and immune changes after an
      ultramarathon.
AB  - The purpose of this randomized study was to measure the influence of vitamin C (n
      = 15 runners) compared with placebo (n = 13 runners) supplementation on oxidative
      and immune changes in runners competing in an ultramarathon race. During the 7
      day period before the race and on race day, subjects ingested in randomized,
      double-blind fashion 1,500 mg/day vitamin C or placebo. On race day, blood
      samples were collected 1 h before race, after 32 km of running, and then again
      immediately after race. Subjects in both groups maintained an intensity of
      approximately 75% maximal heart rate throughout the ultramarathon race and ran a
      mean of 69 km (range: 48-80 km) in 9.8 h (range: 5-12 h). Plasma ascorbic acid
      was markedly higher in the vitamin C compared with placebo group prerace and rose
      more strongly in the vitamin C group during the race (postrace: 3.21 +/- 0.29 and
      1.28 +/- 0.12 microg/100 microl, respectively, P < 0.001). No significant group
      or interaction effects were measured for lipid hydroperoxide, F2-isoprostane,
      immune cell counts, plasma interleukin (IL)-6, IL-10, IL-1-receptor antagonist,
      or IL-8 concentrations, or mitogen-stimulated lymphocyte proliferation and IL-2
      and IFN-gamma production. These data indicate that vitamin C supplementation in
      carbohydrate-fed runners does not serve as a countermeasure to oxidative and
      immune changes during or after a competitive ultramarathon race.

PMID- 11960948
TI  - Effects of muscle activation on fatigue and metabolism in human skeletal muscle.
AB  - Increasing stimulation frequency has been shown to increase fatigue but not when
      the changes in force associated with changes in frequency have been controlled.
      An effect of frequency, independent of force, may be associated with the
      metabolic cost resulting from the additional activations. Here, two separate
      experiments were performed on human medial gastrocnemius muscles. The first
      experiment (n = 8) was designed to test the effect of the number of pulses on
      fatigue. The declines in force during two repetitive, 150-train stimulation
      protocols that produced equal initial forces, one using 80-Hz trains and the
      other using 100-Hz trains, were compared. Despite a difference of 600 pulses
      (23.5%), the protocols produced similar rates and amounts of fatigue. In the
      second experiment, designed to test the effect of the number of pulses on the
      metabolic cost of contraction, 31P-NMR spectra were collected (n = 6) during two
      ischemic, eight-train stimulation protocols (80- and 100-Hz) that produced
      comparable forces despite a difference of 320 pulses (24.8%). No differences were
      found in the changes in P(i) concentration, phosphocreatine concentration, and
      intracellular pH or in the ATP turnover produced by the two trains. These results
      suggest that the effect of stimulation frequency on fatigue is related to the
      force produced, rather than to the number of activations. In addition, within the
      range of frequencies tested, increasing total activations did not increase
      metabolic cost.

PMID- 11960949
TI  - Effects of OSA, inhalational anesthesia, and fentanyl on the airway and
      ventilation of children.
AB  - To assess effects of anesthesia and opioids, we studied 13 children with
      obstructive sleep apnea (OSA, age 4.0 +/- 2.2 yr, mean +/- SD) and 24 age-matched
      control subjects (5.8 +/- 4.0 yr). Apnea indexes of children with OSA were 29.4
      +/- 18 h-1, median 30 h-1. Under inhalational anesthetic, closing pressure at the
      mask was 2.2 +/- 6.9 vs. -14.7 +/- 7.8 cmH2O, OSA vs. control (P < 0.001). After
      intubation, spontaneous ventilation was 115.5 +/- 56.9 vs. 158.7 +/- 81.6 ml x kg
      1 small middle dot min-1, OSA vs. control (P = 0.02), despite elevated PCO2 (49.3
      vs. 42.1 Torr, OSA vs. control, P < 0.001). Minute ventilation fell after
      fentanyl (0.5 microg/kg iv), with central apnea in 6 of 13 OSA cases vs. 1 of 23
      control subjects (P < 0.001). Consistent with the finding of reduced spontaneous
      ventilation, apnea was most likely when end-tidal CO2 exceeded 50 Torr during
      spontaneous breathing under anesthetic. Thus children with OSA had depressed
      spontaneous ventilation under anesthesia, and opioids precipitated apnea in
      almost 50% of children with OSA who were intubated but breathing spontaneously
      under inhalational anesthesia.

PMID- 11960950
TI  - Lengthening contraction-induced inflammation is linked to secondary damage but
      devoid of neutrophil invasion.
AB  - Inflammation triggered by exercise-induced muscle damage (EIMD) has been
      postulated to influence the extent of tissue destruction. We tested the
      hypotheses that 1) repressing inflammation decreases secondary damage production
      and 2) EIMD leads to a sequential appearance of inflammatory cells in which
      neutrophil accumulation precedes macrophage invasion. Rat ankle dorsiflexor
      muscles were submitted to in situ lengthening contractions. Measurement of in
      vitro contractile properties, inflammatory cell concentrations, and histological
      staining were performed postprotocol. Rats were treated with diclofenac, a
      nonsteroidal anti-inflammatory drug (NSAID group) to repress inflammation or with
      the vehicle solution (EIMD group). Muscles from the NSAID group had smaller force
      deficits on days 2 and 3 postexercise. This effect was associated with
      significantly smaller increases in the concentration of muscle macrophage ED1+
      and ED2+. Surprisingly, neutrophils did not accumulate post-EIMD. These results
      suggest that inflammation-induced ED1+ macrophage accumulation is responsible for
      the secondary damage observed 2-3 days post-EIMD. We further conclude that an
      increase in ED1+ macrophage concentration can occur in absence of previous
      neutrophil invasion.

PMID- 11960951
TI  - Involvement of nitric oxide synthase in skeletal muscle adaptation to chronic
      overload.
AB  - The purpose of this study was to determine the necessity of nitric oxide (NO) for
      hypertrophy and fiber-type transition in overloaded (OL) skeletal muscle.
      Endogenous NO production was blocked by administering N(G)-nitro-L-arginine
      methyl ester (L-NAME; 0.75 mg/ml; approximately 100 mg x kg-1 x day-1) in
      drinking water. Thirty-eight female Sprague-Dawley rats (approximately 250 g)
      were randomly divided into four groups: control-nonoverloaded (Non-OL), control
      OL, L-NAME-Non-OL, and L-NAME-OL. Chronic overload of the plantaris was induced
      bilaterally by surgical removal of the gastrocnemius and soleus. Rats in the Non
      OL groups received sham surgeries. L-NAME treatment began 24 h before surgery and
      continued until the rats were killed 14 days postsurgery. Although OL induced
      hypertrophy in both control (+76%) and L-NAME (+39%) conditions (P < 0.05), mean
      plantaris-to-body mass ratio in the L-NAME-OL group was significantly lower (P <
      0.05) than that in the control-OL group. Microphotometric analysis of
      histochemically determined fiber types revealed increases in cross-sectional area
      (P < 0.05) for all fiber types (types I, IIA, and IIB/X) in the OL plantaris from
      control rats, whereas L-NAME-OL rats exhibited increases only in type I and IIB/X
      fibers. SDS-PAGE analysis of myosin heavy chain (MHC) composition in the
      plantaris indicated a significant (P < 0.05) OL effect in the control rats.
      Specifically, the mean proportion of type I MHC increased 6% (P < 0.05), whereas
      the proportion of type IIb MHC decreased approximately 9% (P < 0.05). No
      significant OL effects on MHC profile were observed in the L-NAME rats. These
      data support a role of NO in overload-induced skeletal muscle hypertrophy and
      fiber-type transition.

PMID- 11960952
TI  - Role of nitric oxide in heparin-induced attenuation of hypoxic pulmonary vascular
      remodeling.
AB  - Heparin and nitric oxide (NO) attenuate changes to the pulmonary vasculature
      caused by prolonged hypoxia. Heparin may increase NO; therefore, we hypothesized
      that heparin may attenuate hypoxia-induced pulmonary vascular remodeling via a NO
      mediated mechanism. In vivo, rats were exposed to normoxia (N) or hypoxia (H; 10%
      O(2)) with or without heparin (1,200 U x kg-1 x day-1) and/or the NO synthase
      (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME; 20 mg x kg-1 x day
      1) for 3 days or 3 wk. Heparin attenuated increases in pulmonary arterial
      pressure, the percentage of muscular pulmonary vessels, and their medial
      thickness induced by 3 wk of H. Importantly, although L-NAME alone had no effect,
      it prevented these effects of heparin on vascular remodeling. In H lungs, heparin
      increased NOS activity and cGMP levels at 3 days and 3 wk and endothelial NOS
      protein expression at 3 days but not at 3 wk. In vitro, heparin (10 and 100 U x
      kg-1 x ml-1) increased cGMP levels after 10 min and 24 h in N and anoxic (0% O2)
      endothelial cell-smooth muscle cell (SMC) coculture. SMC proliferation, assessed
      by 5-bromo-2'-deoxyuridine incorporation during a 3-h incubation period, was
      decreased by heparin under N, but not anoxic, conditions. The antiproliferative
      effects of heparin were not altered by L-NAME. In conclusion, the in vivo results
      suggest that attenuation of hypoxia-induced pulmonary vascular remodeling by
      heparin is NO mediated. Heparin increases cGMP in vitro; however, the heparin
      induced decrease in SMC proliferation in the coculture model appears to be NO
      independent.

PMID- 11960953
TI  - Effects of chronic sympathectomy on vascular function in the human forearm.
AB  - To determine whether endothelial function is altered by chronic surgical
      sympathectomy, we infused ACh, isoproterenol, nitroprusside (NTP), and the nitric
      oxide synthase inhibitor NG-mono-methyl-L-arginine (L-NMMA) into the brachial
      arteries of nine patients 5-64 mo after thoracic sympathectomy for hyperhidrosis.
      Age- and gender-matched controls were also studied. Forearm blood flow (FBF) was
      measured by venous occlusion plethysmography. Lower body negative pressure was
      used to assess reflex vasoconstrictor responses. Tyramine, which acts locally and
      causes norepinephrine release from sympathetic nerves, was also administered via
      the brachial artery. FBF at rest was 2.5 +/- 0.4 ml x dl-1 x min-1 in the
      patients and 2.5 +/- 0.3 ml x dl-1 x min-1 in the controls (P = 0.95). The normal
      vasoconstrictor responses to lower body negative pressure were abolished in the
      patients. By contrast, tyramine produced dose-dependent vasoconstriction in the
      patients that was identical to that of controls. The dose-response curves to ACh
      were similar in patients and controls, with maximum values of 19.3 +/- 4.4 vs.
      25.5 +/- 2.8 ml x dl-1 x min-1, respectively. L-NMMA reduced baseline FBF
      similarly and reduced the maximal FBF response to ACh in both groups (patients
      8.9 +/- 3.5 vs. controls 9.7 +/- 2.5 ml x dl-1 x min-1). The vasodilation to
      isoproterenol was similar and blunted to the same extent in both groups by L
      NMMA. The responses to NTP in patients and controls were similar and not affected
      by L-NMMA. We conclude that, in humans, chronic surgical sympathectomy does not
      cause major disruptions in vascular function in the forearm. The normal
      vasoconstrictor responses to tyramine indicate that there were viable sympathetic
      nerves in the forearm that were not engaged by LBNP.

PMID- 11960954
TI  - Role of skin blood flow and sweating rate in exercise thermoregulation after bed
      rest.
AB  - Two potential mechanisms, reduced skin blood flow (SBF) and sweating rate (SR),
      may be responsible for elevated intestinal temperature (T(in)) during exercise
      after bed rest and spaceflight. Seven men underwent 13 days of 6 degrees head
      down bed rest. Pre- and post-bed rest, subjects completed supine submaximal cycle
      ergometry (20 min at 40% and 20 min at 65% of pre-bed rest supine peak exercise
      capacity) in a thermoneutral room. After bed rest, T(in) was elevated at rest
      (+0.31 +/- 0.12 degrees C) and at the end of exercise (+0.33 +/- 0.07 degrees C).
      Percent increase in SBF during exercise was less after bed rest (211 +/- 53 vs.
      96 +/- 31%; P < or = 0.05), SBF/T(in) threshold was greater (37.09 +/- 0.16 vs.
      37.33 +/- 0.13 degrees C; P < or = 0.05), and slope of SBF/T(in) tended to be
      reduced (536 +/- 184 vs. 201 +/- 46%/ degrees C; P = 0.08). SR/T(in) threshold
      was delayed (37.06 +/- 0.11 vs. 37.34 +/- 0.06 degrees C; P < or = 0.05), but the
      slope of SR/T(in) (3.45 +/- 1.22 vs. 2.58 +/- 0.71 mg x min-1 x cm-2 x degrees C
      1) and total sweat loss (0.42 +/- 0.06 vs. 0.44 +/- 0.08 kg) were not changed.
      The higher resting and exercise T(in) and delayed onset of SBF and SR suggest a
      centrally mediated elevation in the thermoregulatory set point during bed rest
      exposure.

PMID- 11960955
TI  - Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant
      male Zucker rats.
AB  - We hypothesized that estradiol treatment would improve vascular dysfunction
      commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham
      operation or 17beta-estradiol pellet implantation was performed in male lean and
      obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and
      potassium chloride was exaggerated in control obese rats compared with lean rats,
      but estradiol significantly attenuated VC in the obese rats. Estradiol reduced
      the PE EC50 in all groups. This effect was cyclooxygenase independent, because
      preincubation with indomethacin reduced VC response to PE similarly in a subset
      of control and estrogen-treated lean rats. Endothelium-independent vasodilation
      (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent
      VD to ACh was significantly impaired in obese compared with lean rats. Estradiol
      improved VD in lean and obese rats by decreasing EC50 but impaired function by
      decreasing maximal VD. The shift in EC50 corresponded to an upregulation in
      nitric oxide synthase III protein expression in the aorta of the estrogen-treated
      obese rats. In summary, estrogen treatment improves vascular function in male
      insulin-resistant, obese rats, partially via an upregulation of nitric oxide
      synthase III protein expression. These effects are counteracted by adverse
      factors, such as hyperlipidemia and, potentially, a release of an endothelium
      derived contractile agent.

PMID- 11960956
TI  - Early changes of type 2B fibers after denervation of rat EDL skeletal muscle.
AB  - Skeletal muscle type 2B fibers normally receive a moderate level of motoneuron
      discharge. As a consequence, we hypothesize that type 2B fiber properties should
      be less sensitive to the absence of the nerve. Therefore, we have investigated
      the response of sarcoplasmic reticulum and myofibrillar proteins of type 2B
      fibers isolated from rat extensor digitorum longus muscle after denervation (2
      and 7 days). Single fibers were identified by SDS-PAGE of myosin heavy chain
      isoforms. Electrophysiological and isometric contractile properties of the whole
      muscle were also analyzed. The pCa-tension relationship of type 2B single fibers
      was shifted to the left at 2 days and to right at 7 days after denervation, with
      significant differences in the Hill coefficients and pCa threshold values in 2-
      vs. 7-day-denervated fibers. The sarcoplasmic reticulum Ca2+ uptake capacity and
      rate significantly decreased after 2 days of denervation, whereas both increased
      at 7 days. Caffeine sensitivity of sarcoplasmic reticulum Ca2+ release was
      transitory and markedly increased in 2-day-denervated fibers. Our results
      indicate that type 2B fiber functional properties are highly sensitive to the
      interruption of nerve supply. Moreover, most of 2-day-denervated changes were
      reverted at 7 days.

PMID- 11960957
TI  - Gender governs the relationship between exercise intensity and growth hormone
      release in young adults.
AB  - We previously reported that in young adult males growth hormone (GH) release is
      related to exercise intensity in a linear dose-response manner (Pritzlaff et al.
      J Appl Physiol 87: 498-504, 1999). To investigate the effects of gender and
      exercise intensity on GH release, eight women (24.3 +/- 1.3 yr, 171 +/- 3.2 cm
      height, 63.6 +/- 8.7 kg weight) were each tested on six randomly ordered
      occasions [1 control condition (C), 5 exercise conditions (Ex)]. Serum GH
      concentrations were measured in samples obtained at 10-min intervals between 0700
      and 0900 (baseline) and 0900 and 1300 (Ex + recovery or C). Integrated GH
      concentrations (IGHC) were calculated by trapezoidal reconstruction. During Ex,
      subjects exercised for 30 min (0900-0930) at one of the following intensities
      [normalized to the lactate threshold (LT)]: 25 and 75% of the difference between
      LT and rest, at LT, and at 25 and 75% of the difference between LT and peak O2
      uptake. No differences were observed among conditions for baseline IGHC. To
      determine whether total (Ex + recovery) IGHC changed with increasing exercise
      intensity, slopes associated with individual linear regression models were
      subjected to a Wilcoxon signed-rank test. To test for gender differences, data in
      women were compared with the previously published data in men. A Wilcoxon ranked
      sums two-tailed test was used to analyze the slopes and intercepts from the
      regression models. Total IGHC increased linearly with increasing exercise
      intensity. The slope and intercept values for the relationship between total IGHC
      and exercise intensity were greater in women than in men. Deconvolution analysis
      (0700-1300 h) revealed that, regardless of gender, increasing exercise intensity
      resulted in a linear increase in the mass of GH secreted per pulse and summed GH
      production rate, with no changes in GH secretory pulse frequency or apparent half
      life of elimination. Exercise reduced the half-duration of GH secretory burst in
      men but not in women. Gender comparisons revealed that women had greater basal
      (nonpulsatile) GH secretion across all conditions, more frequent GH secretory
      pulses, a greater GH secretory pulse amplitude, a greater production rate, and a
      trend for a greater mass of GH secreted per pulse than men. We conclude that, in
      young adults, the GH secretory response to exercise is related to exercise
      intensity in a linear dose-response pattern. For each incremental increase in
      exercise intensity, the fractional stimulation of GH secretion is greater in
      women than in men.

PMID- 11960958
TI  - Metabolic and appetite responses to prolonged walking under three isoenergetic
      diets.
AB  - The effects of three isoenergetic diets on metabolic and appetite responses to
      prolonged intermittent walking were investigated. Eight men undertook three 450
      min walks at intensities varying between 25-30 and 50-55% of maximal O2 uptake.
      In a balanced design, the subjects were given breakfast, snacks, and lunch
      containing total carbohydrate (CHO), protein (P), and fat (F) in the following
      amounts (g/70 kg body mass): mixed diet, 302 CHO, 50 P, 84 F; high-CHO diet, 438
      CHO, 46 P, 35 F; high-fat diet, 63 CHO, 44 P, 196 F. Substrate balance was
      calculated by indirect calorimetry over the 450-min exercise period. Blood
      samples were taken before exercise and every 45 min during the exercise period.
      The high-fat diet resulted in a negative total CHO balance (-140 +/- 1 g) and a
      lower negative fat balance (-110 +/- 33 g) than the other two diets (P < 0.05).
      Plasma glucagon, nonesterified fatty acids, glycerol, and 3-hydroxybutyrate were
      higher with the high-fat diet (P < 0.05 vs. high CHO), whereas plasma insulin was
      lower after high fat (P < 0.05 vs. mixed and high CHO). Subjective ratings of
      fatigue and appetite showed no differences between the three trials. Although
      diet influenced the degree of total CHO and fat oxidation, fat was the main
      source of energy in all trials.

PMID- 11960959
TI  - The human spleen as an erythrocyte reservoir in diving-related interventions.
AB  - Twelve subjects without and ten subjects with diving experience performed short
      diving-related interventions. After labeling of erythrocytes, scintigraphic
      measurements were continuously performed during these interventions. All
      interventions elicited a graduated and reproducible splenic contraction,
      depending on the type, severity, and duration of the interventions. The splenic
      contraction varied between approximately 10% for "apnea" (breath holding for 30
      s) and "cold clothes" (cold and wet clothes applied on the face with no breath
      holding for 30 s) and approximately 30-40% for "simulated diving" (simulated
      breath-hold diving for 30 s), "maximal apnea" (breath holding for maximal
      duration), and "maximal simulated diving" (simulated breath-hold diving for
      maximal duration). The strongest interventions (simulated diving, maximal apnea,
      and maximal simulated diving) elicited modest but significant increases in
      hemoglobin concentration (0.1-0.3 mmol/l) and hematocrit (0.3-1%). By an indirect
      method, the splenic venous hematocrit was calculated to 79%. No major differences
      were observed between the two groups. The splenic contraction should, therefore,
      be included in the diving response on equal terms with bradycardia, decreased
      peripheral blood flow, and increased blood pressure.

PMID- 11960960
TI  - Regulation of flow and wall shear stress in arteriolar networks of the hamster
      cheek pouch.
AB  - Our purpose was to define arteriolar network hemodynamics during moderate
      increases in interstitial adenosine or nitric oxide in the hamster (n = 34,
      pentobarbital sodium 70 mg/kg) cheek pouch tissue. The network consists of a feed
      arteriole (approximately 12-microm diameter, approximately 800-microm length)
      with three to six branches. Observations of diameter, red blood cell flux, and
      velocity were obtained at the feed before the branch and within the branch. A
      comparison of baseline with suffused adenosine or sodium nitroprusside (SNP) 10(
      9) to 10(-5) M showed the following. First, diameter change was heterogeneous by
      agonist, did not reflect the expected dilatory response, and was related to
      location within the network. With adenosine, upstream branch points constricted
      and those downstream dilated, even at 10(-5) M. With SNP, upstream branch points
      dilated, whereas those downstream constricted. Second, with adenosine, changes in
      diameter, flux, and velocity together resulted in no change in wall shear stress
      until 10(-5) M. Wall shear stress was not maintained at a constant level with
      Nomega-nitro-L-arginine (10(-5) M), suggesting a role for flow-dependent diameter
      changes with adenosine. With SNP, diameter change correlated with the baseline
      (before SNP) shear stress conditions.

PMID- 11960961
TI  - In situ rat fast skeletal muscle is more efficient at submaximal than at maximal
      activation levels.
AB  - The influence of stimulation frequency on efficiency (= total work output/high
      energy phosphate consumption) was studied using in situ medial gastrocnemius
      muscle tendon complexes of the rat. The muscles performed 20 repeated concentric
      contractions (2/s) at 34 degrees C. During these repeated contractions, the
      muscle was stimulated via the severed sciatic nerve with either 60, 90, or 150
      Hz. The muscle was freeze-clamped immediately after these contractions, and high
      energy phosphate consumption was determined by measuring intramuscular chemical
      change relative to control muscles. The average values (+/-SD) of efficiency
      calculated for 60, 90, and 150 Hz were 18.5 +/- 1.5 (n = 7), 18.6 +/- 1.5 (n =
      9), and 14.7 +/- 1.3 mJ/micromol phosphate (n = 9). The results indicate that the
      efficiency of the muscles that were submaximally activated (60 or 90 Hz) was
      higher (+26%, P < 0.05) than that of those maximally activated (150 Hz).
      Additional experiments showed that the low efficiency at maximal activation
      levels is unlikely to be the result of a higher energy turnover by the Ca2+ 
      ATPase relative to the total energy turnover. Therefore, alternative explanations
      are discussed.

PMID- 11960962
TI  - Low sodium intake does not impair renal compensation of hypoxia-induced
      respiratory alkalosis.
AB  - Acute hypoxia causes hyperventilation and respiratory alkalosis, often combined
      with increased diuresis and sodium, potassium, and bicarbonate excretion. With a
      low sodium intake, the excretion of the anion bicarbonate may be limited by the
      lower excretion rate of the cation sodium through activated sodium-retaining
      mechanisms. This study investigates whether the short-term renal compensation of
      hypoxia-induced respiratory alkalosis is impaired by a low sodium intake. Nine
      conscious, tracheotomized dogs were studied twice either on a low-sodium (LS =
      0.5 mmol sodium x kg body wt-1 x day-1) or high-sodium (HS = 7.5 mmol sodium x kg
      body wt-1 x day-1) diet. The dogs breathed spontaneously via a ventilator circuit
      during the experiments: first hour, normoxia (inspiratory oxygen fraction =
      0.21); second to fourth hour, hypoxia (inspiratory oxygen fraction = 0.1). During
      hypoxia (arterial PO2 34.4 +/- 2.1 Torr), plasma pH increased from 7.37 +/- 0.01
      to 7.48 +/- 0.01 (P < 0.05) because of hyperventilation (arterial PCO2 25.6 +/-
      2.4 Torr). Urinary pH and urinary bicarbonate excretion increased irrespective of
      the sodium intake. Sodium excretion increased more during HS than during LS,
      whereas the increase in potassium excretion was comparable in both groups. Thus
      the quick onset of bicarbonate excretion within the first hour of hypoxia-induced
      respiratory alkalosis was not impaired by a low sodium intake. The increased
      sodium excretion during hypoxia seems to be combined with a decrease in plasma
      aldosterone and angiotensin II in LS as well as in HS dogs. Other factors, e.g.,
      increased mean arterial blood pressure, minute ventilation, and renal blood flow,
      may have contributed.

PMID- 11960963
TI  - Heterogeneous responses of human limbs to infused adrenergic agonists: a
      gravitational effect?
AB  - Unlike quadrupeds, the legs of humans are regularly exposed to elevated pressures
      relative to the arms. We hypothesized that this "dependent hypertension" would be
      associated with altered adrenergic responsiveness. Isoproterenol (0.75-24 ng x
      100 ml limb volume-1 x min-1) and phenylephrine (0.025-0.8 microg x 100 ml limb
      volume-1 x min-1) were infused incrementally in the brachial and femoral arteries
      of 12 normal volunteers; changes in limb blood flow were quantified by using
      strain-gauge plethysmography. Compared with the forearm, baseline calf vascular
      resistance was greater (38.8 +/- 2.5 vs. 26.9 +/- 2.0 mmHg x 100 ml x min x ml-1;
      P < 0.001) and maximal conductance was lower (46.1 +/- 11.9 vs. 59.4 +/- 13.4 ml
      x ml-1 x min-1 x mmHg-1; P < 0.03). Vascular conductance did not differ between
      the two limbs during isoproterenol infusions, whereas decreases in vascular
      conductance were greater in the calf than the forearm during phenylephrine
      infusions (P < 0.001). With responses normalized to maximal conductance, the half
      maximal response for phenylephrine was significantly less for the calf than the
      forearm (P < 0.001), whereas the half-maximal response for isoproterenol did not
      differ between limbs. We conclude that alpha1- but not beta-adrenergic-receptor
      responsiveness in human limbs is nonuniform. The relatively greater response to
      alpha1-adrenergic-receptor stimulation in the calf may represent an adaptive
      mechanism that limits blood pooling and capillary filtration in the legs during
      standing.

PMID- 11960964
TI  - Respiratory events and periodic breathing in cyclists sleeping at 2,650-m
      simulated altitude.
AB  - We examined the initial effect of sleeping at a simulated moderate altitude of
      2,650 m on the frequency of apneas and hypopneas, as well as on the heart rate
      and blood oxygen saturation from pulse oximetry (SpO2) during rapid eye movement
      (REM) and non-rapid eye movement (NREM) sleep of 17 trained cyclists. Pulse
      oximetry revealed that sleeping at simulated altitude significantly increased
      heart rate (3 +/- 1 beats/min; means +/- SE) and decreased SpO2 (-6 +/- 1%)
      compared with baseline data collected near sea level. In response to simulated
      altitude, 15 of the 17 subjects increased the combined frequency of apneas plus
      hypopneas from baseline levels. On exposure to simulated altitude, the increase
      in apnea was significant from baseline for both sleep states (2.0 +/- 1.3
      events/h for REM, 9.9 +/- 6.2 events/h for NREM), but the difference between the
      two states was not significantly different. Hypopnea frequency was significantly
      elevated from baseline to simulated altitude exposure in both sleep states, and
      under hypoxic conditions it was greater in REM than in NREM sleep (7.9 +/- 1.8
      vs. 4.2 +/- 1.3 events/h, respectively). Periodic breathing episodes during sleep
      were identified in four subjects, making this the first study to show periodic
      breathing in healthy adults at a level of hypoxia equivalent to 2,650-m altitude.
      These results indicate that simulated moderate hypoxia of a level typically
      chosen by coaches and elite athletes for simulated altitude programs can cause
      substantial respiratory events during sleep.

PMID- 11960965
TI  - CO2 dialysis in nucleus tractus solitarius region of rat increases ventilation in
      sleep and wakefulness.
AB  - To evaluate the function of widely distributed central chemoreceptors during
      sleep and wakefulness in the rat, we focally stimulate single chemoreceptor sites
      during naturally occurring sleep-wake cycles by microdialysis of artificial
      cerebrospinal fluid equilibrated with 25% CO2. In retrotrapezoid nucleus, this
      increased ventilation (tidal volume) by 24% only in wakefulness (Li A, Randall M,
      and Nattie E. J Appl Physiol 87: 910-919, 1999). In caudal medullary raphe, it
      increased ventilation (frequency) by 15-20% only in sleep (Nattie EE and Li A. J
      Appl Physiol 90: 1247-1257, 2001). Here, in nucleus tractus solitarius (NTS),
      focal acidification significantly increased ventilation by 11% in sleep and 7% in
      wakefulness rostrally (n = 5) and by 16% in sleep and 28% in wakefulness caudally
      (n = 5). The sleep-wake cycle was unaltered. Dialysis with 5% CO2 had no effect.
      Dialysis with 50% CO2 caudally did not further stimulate ventilation but did
      disrupt sleep. Central chemoreceptors in the NTS affect breathing in both sleep
      and wakefulness. The threshold for arousal in caudal NTS is greater than that for
      the stimulation of breathing.

PMID- 11960966
TI  - Alterations in corticospinal excitability with imposed vs. voluntary fatigue in
      human hand muscles.
AB  - We aimed to determine whether postexercise depression of motor-evoked potentials
      (MEPs) could be demonstrated without voluntary muscle activation in humans.
      Voluntary fatigue was induced with a 2-min maximal voluntary contraction (MVC) of
      the first dorsal interosseous (FDI) muscle. On another occasion, "electrical
      fatigue" was induced with trains of shocks delivered for 2 min over the FDI motor
      point. Five of the twelve subjects also underwent "sequential fatigue" consisting
      of a 2-min MVC of FDI followed by 20 min of rest and then 2 min of motor point
      stimulation. Voluntary fatigue induced MEP depression that persisted for at least
      20 min. Electrical fatigue induced a transient MEP facilitation that subsided 20
      min after the stimulation and became depressed within 30 min. Thus MEP depression
      can be induced by both voluntary and electrical fatigue. With electrical fatigue,
      the initial depression is "masked" by transient MEP facilitation, reflecting
      cortical plasticity induced by the prolonged electrical stimulation. MEP
      depression probably reflects tonic afferent input from the exercising muscle that
      alters cortical excitability without altering spinal excitability.

PMID- 11960967
TI  - Effects of albumin supplementation on microvascular permeability in septic
      patients.
AB  - Albumin has a stabilizing effect on endothelium and helps maintain capillary
      permeability to macromolecules. Critically ill patients with sepsis may have
      profound hypoalbuminemia, but the effect of this hypoalbuminemia on microvascular
      permeability is unknown. To determine the degree and potential importance of this
      effect, we measured the transcapillary escape rate (TER) of (125)I-labeled
      albumin in 12 adult patients fulfilling American College of Chest
      Physicians/Society of Critical Care Medicine criteria for septic shock. We
      measured TER over a 90-min baseline period and then repeated these measurements
      immediately after the rapid infusion of 200 ml of 20% albumin. At baseline,
      patients had a mean serum albumin concentration of 10.3 +/- 3.8 g/l, which, at 30
      min after the albumin infusion, was 18.5 +/- 3.7 g/l. The baseline TER was 6.7 +/
      1.5%/h, with a postinfusion TER of 6.4 +/- 2.1%/h (P = 0.550). Albumin
      supplementation sufficient to nearly double serum concentrations in profoundly
      hypoalbuminemic septic patients had no clinically significant effect in reducing
      microvascular permeability.

PMID- 11960968
TI  - Gender-related differences in elite gymnasts: the female athlete triad.
AB  - High-intensity training can alter the normal pattern of pubertal development in
      elite gymnasts. We investigated sex hormones, the ob gene product leptin, body
      composition, nutrition, and eating habits in female and male elite gymnasts from
      national cadres to elucidate gender-related differences. Serum leptin levels were
      decreased, particularly in pubertal girls, and did not show the normal
      developmental pattern. After leptin levels were transformed into standard
      deviation scores, mainly pubertal female gymnasts had significantly lower values
      than normal controls of the same gender, pubertal stage, and body mass index. The
      percentage of body fat was reduced compared with a normal age-matched population
      in both genders but to a higher degree in female gymnasts. When leptin standard
      deviation scores were based on percent body fat instead of body mass index, mean
      values were still significantly decreased compared with those of normal controls:
      -1.05 in girls (P < 0.001) and -0.60 in boys (P = 0.025). In both genders, total
      energy consumption and nutritional intake were insufficient, although to a lesser
      extent in male gymnasts. Pubertal development is influenced to a different degree
      in female and male elite gymnasts. In contrast to their male counterparts, high
      intensity training takes place during the sensitive phase of pubertal maturation
      in female gymnasts. Whereas the girls displayed low estrogen levels,
      hypoleptinemia, reduced body fat mass, insufficient caloric intake, and retarded
      menarche, the pubertal development of male gymnasts remained almost unaltered.

PMID- 11960969
TI  - Expression of angiotensin II type 1 (AT(1)) receptor in the rostral ventrolateral
      medulla in rats.
AB  - In the present study, the changes of amino acids release in the spinal cord after
      the application of angiotensin II (ANG II) in the rostral ventrolateral medulla
      (RVLM) and the distribution of ANG receptors on neurons of the RVLM were
      investigated. A microdialysis experiment showed that microinjection of
      angiotensin II into the RVLM significantly (P < 0.01) increased the release of
      aspartate and glutamate in the intermediolateral column of the spinal cord.
      Immunofluorescence technique combined with confocal microscopy demonstrated that
      most of the glutamatergic and GABAergic neurons in the RVLM of both Wistar and
      spontaneously hypertensive rats (SHR) were double labeled with ANG type 1 (AT1)
      receptor. Immunocytochemical studies demonstrated that the mean optic density of
      AT1 receptor of the cell surface as well as the whole cell was higher (P < 0.05)
      in SHR than that in Wistar rats, indicating that the higher expression of AT1
      receptors in the RVLM may contribute to the higher responsiveness of SHR to ANG
      II stimulation. Immunogold staining and electronmicroscopic study demonstrated
      that AT1 receptor in the RVLM was distributed on the rough endoplasmic reticulum,
      cell membrane, and nerve processes. The results suggest that effects evoked by
      ANG II in the RVLM are closely related to glutamatergic and GABAergic pathways.
      These results indirectly support the hypothesis that ANG II in the RVLM may
      activate vasomotor sympathetic glutamatergic neurons, leading to an increase in
      sympathetic nerve activity and arterial blood pressure.

PMID- 11960970
TI  - Effects of all-trans retinoic acid on angiotensin II-induced myocyte hypertrophy.
AB  - We used cultured neonatal rat cardiac myocytes to test the hypothesis that all
      trans retinoic acid (atRA) may act to modulate ANG II actions in inducing myocyte
      hypertrophy. Our observations were as follows. 1) atRA (10(-7) to approximately
      10(-5) M ) inhibited ANG II-induced hyperplasia of fibroblasts in a dose
      dependent manner. 2) Treatment of atRA attenuated the ANG II-induced increase in
      total cell protein content. 3) Treated with ANG II (10(-7) M) for 5 days, the
      cultured neonatal rat cardiac myocytes demonstrated an apparent accumulation of
      sarcomeric fiber proteins and Golgi's complex, as well as reorganization of the
      sarcomeric unit within individual myocytes. atRA (10(-6) M) treatment reduced the
      accumulation of contractile proteins and Golgi's complex without affecting the
      ANG II-induced reorganization of the sarcomeric unit. 4) atRA attenuated the ANG
      II-induced increase in intracellular Ca2+. Our results show that atRA inhibits
      some effects of ANG II on neonatal rat cardiac myocytes and suggest that atRA may
      be a therapeutic candidate for the prevention and therapy of cardiac hypertrophy
      and remodeling.

PMID- 11960971
TI  - Characterization of LPS-induced lung inflammation in cftr-/- mice and the effect
      of docosahexaenoic acid.
AB  - The mechanism by which Pseudomonas causes excessive inflammation in the cystic
      fibrosis lung is unclear. We have reported that arachidonic acid is increased and
      docosahexaenoic acid (DHA) decreased in lung, pancreas, and ileum from cftr-/-
      mice. Oral DHA corrected this defect and reversed the pathology. To determine
      which mediators regulate inflammation in lungs from cftr-/- mice and whether
      inhibition occurs with DHA, cftr-/- and wild-type (WT) mice were exposed to
      aerosolized Pseudomonas lipopolysaccharide (LPS). After 2 days of LPS, tumor
      necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2, and KC
      levels in bronchoalveolar lavage fluid were increased in cftr-/- compared with WT
      mice and not suppressed by pretreatment with oral DHA. Neutrophil levels were not
      different between cftr-/- and WT mice. After 3 days of aerosolized LPS,
      neutrophil concentration, TNF-alpha, and the eicosanoids 6-keto-PGF1alpha,
      PGF2alpha, PGE2, and thromboxane B2 were all increased in bronchoalveolar lavage
      fluid from cftr-/- mice compared with WT controls. Oral DHA had no significant
      effect on TNF-alpha levels in cftr-/- mice. In contrast, neutrophils and
      eicosanoids were decreased in cftr-/- but not in WT mice treated with DHA,
      indicating that the effects of DHA on these inflammatory parameters may be
      related to correction of the membrane lipid defect.

PMID- 11960972
TI  - Heat shock proteins: modifying factors in physiological stress responses and
      acquired thermotolerance.
AB  - Cells from virtually all organisms respond to a variety of stresses by the rapid
      synthesis of a highly conserved set of polypeptides termed heat shock proteins
      (HSPs). The precise functions of HSPs are unknown, but there is considerable
      evidence that these stress proteins are essential for survival at both normal and
      elevated temperatures. HSPs also appear to play a critical role in the
      development of thermotolerance and protection from cellular damage associated
      with stresses such as ischemia, cytokines, and energy depletion. These
      observations suggest that HSPs play an important role in both normal cellular
      homeostasis and the stress response. This mini-review examines recent evidence
      and hypotheses suggesting that the HSPs may be important modifying factors in
      cellular responses to a variety of physiologically relevant conditions such as
      hyperthermia, exercise, oxidative stress, metabolic challenge, and aging.

PMID- 11960973
TI  - Uncoupling proteins and thermoregulation.
AB  - Energy balance in animals is a metabolic state that exists when total body energy
      expenditure equals dietary energy intake. Energy expenditure, or thermogenesis,
      can be subcategorized into groups of obligatory and facultative metabolic
      processes. Brown adipose tissue (BAT), through the activity of uncoupling protein
      1 (UCP1), is responsible for nonshivering thermogenesis, a major component of
      facultative thermogenesis in newborn humans and in small mammals. UCP1, found in
      the mitochondrial inner membrane in BAT, uncouples energy substrate oxidation
      from mitochondrial ATP production and hence results in the loss of potential
      energy as heat. Mice that do not express UCP1 (UCP1 knockouts) are markedly cold
      sensitive. The recent identification of four new homologs to UCP1 expressed in
      BAT, muscle, white adipose tissue, brain, and other tissues has been met by
      tremendous scientific interest. The hypothesis that the novel UCPs may regulate
      thermogenesis and/or fatty acid metabolism guides investigations worldwide.
      Despite several hundred publications on the new UCPs, there are a number of
      significant controversies, and only a limited understanding of their
      physiological and biochemical properties has emerged. The discovery of UCP
      orthologs in fish, birds, insects, and even plants suggests the widespread
      importance of their metabolic functions. Answers to fundamental questions
      regarding the metabolic functions of the new UCPs are thus pending and more
      research is needed to elucidate their physiological functions. In this review, we
      discuss recent findings from mammalian studies in an effort to identify potential
      patterns of function for the UCPs.

PMID- 11960976
TI  - Effect of acute heat shock on gene expression by human peripheral blood
      mononuclear cells.
AB  - We studied the effect of heat shock on gene expression by normal human cells.
      Peripheral blood mononuclear cells (PBMCs) were obtained from healthy adults.
      Paired samples from each subject were subjected to either 20 min of heat shock
      (43 degrees C) or control (37 degrees C) conditions and then returned to 37
      degrees C. RNA was isolated 160 min later, and five representative samples were
      analyzed on Affymetrix gene chip arrays containing approximately 12,600 probes. A
      biologically meaningful effect was defined as a statistically significant,
      twofold or greater difference in expression of sequences that were detected in
      all five experiments under control (downregulated sequences) or heat shock
      (upregulated sequences) conditions. Changes occurred in 395 sequences (227
      increased by heat shock, 168 decreased), representing 353 Unigene numbers, in
      every functional category previously implicated in the heat shock response. By RT
      PCR, we confirmed the findings for one upregulated sequence (Rad, a G protein)
      and one downregulated sequence (osteopontin, a cytokine). We conclude that heat
      shock causes extensive gene expression changes in PBMCs, affecting all functional
      categories of the heat shock response.

PMID- 11960975
TI  - Hypothermic protection of the ischemic heart via alterations in apoptotic
      pathways as assessed by gene array analysis.
AB  - Hypothermia improves resistance to ischemia in the cardioplegia-arrested heart.
      This adaptive process produces changes in specific signaling pathways for
      mitochondrial proteins and heat-shock response. To further test for hypothermic
      modulation of other signaling pathways such as apoptosis, we used various
      molecular techniques, including cDNA arrays. Isolated rabbit hearts were perfused
      and exposed to ischemic cardioplegic arrest for 2 h at 34 degrees C [ischemic
      group (I); n = 13] or at 30 degrees C before and during ischemia [hypothermic
      group (H); n = 12]. Developed pressure, the maximum first derivative of left
      ventricular pressure, oxygen consumption, and pressure-rate product (P < 0.05)
      recovery were superior in H compared with in I during reperfusion. mRNA
      expression for the mitochondrial proteins, adenine translocase and the beta
      subunit of F1-ATPase, was preserved by hypothermia. cDNA arrays revealed that
      ischemia altered expression of 13 genes. Hypothermia modified this response to
      ischemia for eight genes, six related to apoptosis. A marked, near fivefold
      increase in transformation-related protein 53 in I was virtually abrogated in H.
      Hypothermia also increased expression for the anti-apoptotic Bcl-2 homologue Bcl
      x relative to I but decreased expression for the proapoptotic Bcl-2 homologue
      bak. These data imply that hypothermia modifies signaling pathways for apoptosis
      and suggest possible mechanisms for hypothermia-induced myocardial protection.

PMID- 11960977
TI  - Identification of functionally important residues of the epidermal growth factor
      2 domain of factor IX by alanine-scanning mutagenesis. Residues Asn(89)-Gly(93)
      are critical for binding factor VIIIa.
AB  - This paper describes the consequences of alanine-scanning mutagenesis on 28
      positions of the second epidermal growth factor (EGF-2) domain of factor IX. We
      identified four positions of Gln(97), Phe(98), Tyr(115), and Leu(117) that are
      critical for secretion of factor IX. Of the remaining mutations, 4 mutants (V86A,
      E113A, K122A, and S123A) are as active as wild-type factor IX (IXwt); 16 (D85A,
      K100A, N101A, D104A, N105A, R116A, E119A, T87A, I90A, K91A, R94A, E96A, S102A,
      K106A, T112A, and N120A) retain reduced but detectable activity, and 4 (N89A,
      N92A, G93A, and V107A) are nearly inert in the clotting assay. Both factor XIa
      and the factor VIIa-tissue factor complex effectively catalyzed the activation of
      these mutants except N89A. The mutant V107A failed to form the factor tenase
      complex with factor VIIIa because of a 35-fold increase in K(d). The mutants N89A
      and N92A did not compete with factor IXwt for factor VIIIa binding, and G93A
      exhibited a 6-fold increase in K(i) values in the competitive binding assay. It
      appears that mutations at these positions have significantly affected the
      interaction between factor IX and factor VIIIa, although other mutations had
      little effect on the binding of factor IX to factor VIIIa. Mutations in two
      regions, Thr(87)-Gly(93) and Asn(101)-Val(107), significantly increased the K(m)
      value of factor IXa (2-10-fold) in cleavage of factor X in the absence of factor
      VIIIa. In the presence of factor VIIIa, the catalytic efficiency of each mutant
      toward factor X paralleled its clotting activity. Briefly, we propose two
      relatively distinctive functions of factor IX for two adjacent regions in the EGF
      2 domain; the first loop region (residues 89-94) is involved with the binding of
      its cofactor, factor VIIIa, and the third loop with connected beta-sheets
      (residues 102-108) is involved in the proper binding to the substrate, factor X.

PMID- 11960978
TI  - Evidence for a transition state analog, MgADP-aluminum fluoride-acetate, in
      acetate kinase from Methanosarcina thermophila.
AB  - Aluminum fluoride has become an important tool for investigating the mechanism of
      phosphoryl transfer, an essential reaction that controls a host of vital cell
      functions. Planar AlF(3) or AlF(4)(-) molecules are proposed to mimic the
      phosphoryl group in the catalytic transition state. Acetate kinase catalyzes
      phosphoryl transfer of the ATP gamma-phosphate to acetate. Here we describe the
      inhibition of acetate kinase from Methanosarcina thermophila by preincubation
      with MgCl(2), ADP, AlCl(3), NaF, and acetate. Preincubation with butyrate in
      place of acetate did not significantly inhibit the enzyme. Several NTPs can
      substitute for ATP in the reaction, and the corresponding NDPs, in conjunction
      with MgCl(2), AlCl(3), NaF, and acetate, inhibit acetate kinase activity.
      Fluorescence quenching experiments indicated an increase in binding affinity of
      acetate kinase for MgADP in the presence of AlCl(3), NaF, and acetate. These and
      other characteristics of the inhibition indicate that the transition state
      analog, MgADP-aluminum fluoride-acetate, forms an abortive complex in the active
      site. The protection from inhibition by a non-hydrolyzable ATP analog or
      acetylphosphate, in conjunction with the strict dependence of inhibition on the
      presence of both ADP and acetate, supports a direct in-line mechanism for acetate
      kinase.

PMID- 11960979
TI  - Complex regulation of human neuronal nitric-oxide synthase exon 1c gene
      transcription. Essential role of Sp and ZNF family members of transcription
      factors.
AB  - Neuronal nitric-oxide synthase (nNOS) is expressed in a variety of human tissues
      and shows a complex transcriptional regulation with the presence of nine
      alternative first exons (1a-1i) resulting in nNOS transcripts with differing 5'
      untranslated regions. We previously demonstrated that nNOS exon 1c, one of the
      predominant transcripts in the human gastrointestinal tract, is driven by a
      separate promoter (Saur, D., Paehge, H., Schusdziarra, V., and Allescher, H. D.
      (2000) Gastroenterology 118, 849-858). The present study focused on the
      quantitative expression of nNOS first exon variants in different human tissues
      and the characterization of the basal nNOS exon 1c promoter. In human brain,
      skeletal muscle, colon, and TGW-nu-I neuroblastoma cells, first exon expression
      patterns were analyzed by quantitative real-time reverse transcription-PCR. In
      these tissues/cells exon 1c was one of the most abundant first exons of nNOS. By
      transient transfections of TGW-nu-I and HeLa cells with reporter plasmids
      containing a series of 5' and 3' deletions in the exon 1c regulatory region, the
      minimal TATA-less promoter was localized within 44 base pairs. Gel mobility shift
      assays of this cis-regulatory region revealed a high complexity of the basal
      promoter with a cooperative binding of several transcription factors, like Sp and
      ZNF family members. When the Sp binding site of the minimal promoter construct
      was mutated, promoter activity was completely abolished in both cell lines,
      whereas mutation of the common binding site of ZNF76 and ZNF143 resulted in a
      decrease of 53% in TGW-nu-I and 37% in HeLa cells. In Drosophila Schneider cells
      expression of Sp1, the long Sp3 isoform, ZNF76 and ZNF143 potently transactivated
      the nNOS exon 1c promoter. These results identify the critical regulatory region
      for the nNOS exon 1c basal promoter and stress the functional importance of
      multiple protein complexes involving Sp and ZNF families of transcription factors
      in regulating nNOS exon 1c transcription.

PMID- 11960980
TI  - The bone-specific transcriptional regulator Cbfa1 is a target of mechanical
      signals in osteoblastic cells.
AB  - A primary goal of bone research is to understand the mechanism(s) by which
      mechanical forces dictate the cellular and metabolic activities of osteoblasts,
      the bone-forming cells. Several studies indicate that osteblastic cells respond
      to physical loading by transducing signals that alter gene expression patterns.
      Accumulated data have documented the fundamental role of the osteoblast-specific
      transcription factor Cbfa1 (core-binding factor) in osteoblast differentiation
      and function. Here, we demonstrate that low level mechanical deformation
      (stretching) of human osteoblastic cells directly up-regulates the expression and
      DNA binding activity of Cbfa1. This effect seems to be fine tuned by stretch
      triggered induction of distinct mitogen-activated protein kinase cascades. Our
      novel finding that activated extracellular signal-regulated kinase mitogen
      activated protein kinase physically interacts and phosphorylates endogenous Cbfa1
      in vivo (ultimately potentiating this transcription factor) provides a molecular
      link between mechanostressing and stimulation of osteoblast differentiation.
      Elucidation of the specific modifiers and cofactors that operate in this
      mechanotranscription circuitry will contribute to a better understanding of
      mechanical load-induced bone formation which may set the basis for
      nonpharmacological intervention in bone loss pathologies.

PMID- 11960981
TI  - Activation of the cation channel long transient receptor potential channel 2
      (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of activation
      independent of ADP-ribose.
AB  - LTRPC2 is a cation channel recently reported to be activated by adenosine
      diphosphate-ribose (ADP-ribose) and NAD. Since ADP-ribose can be formed from NAD
      and NAD is elevated during oxidative stress, we studied whole cell currents and
      increases in the intercellular free calcium concentration ([Ca(2+)](i)) in long
      transient receptor potential channel 2 (LTRPC2)-transfected HEK 293 cells after
      stimulation with hydrogen peroxide (H(2)O(2)). Cation currents carried by
      monovalent cations and Ca(2+) were induced by H(2)O(2) (5 mm in the bath
      solution) as well as by intracellular ADP-ribose (0.3 mm in the pipette solution)
      but not by NAD (1 mm). H(2)O(2)-induced currents developed slowly after a
      characteristic delay of 3-6 min and receded after wash-out of H(2)O(2).
      [Ca(2+)](i) was rapidly increased by H(2)O(2) in LTRPC2-transfected cells as well
      as in control cells; however, in LTRPC2-transfected cells, H(2)O(2) evoked a
      second delayed rise in [Ca(2+)](i). A splice variant of LTRPC2 with a deletion in
      the C terminus (amino acids 1292-1325) was identified in neutrophil granulocytes.
      This variant was stimulated by H(2)O(2) as the wild type. However, it did not
      respond to ADP-ribose. We conclude that activation of LTRPC2 by H(2)O(2) is
      independent of ADP-ribose and that LTRPC2 may mediate the influx of Na(+) and
      Ca(2+) during oxidative stress, such as the respiratory burst in granulocytes.

PMID- 11960982
TI  - Molecular determinants of voltage-dependent human ether-a-go-go related gene
      (HERG) K+ channel block.
AB  - The structural determinants for the voltage-dependent block of ion channels are
      poorly understood. Here we investigate the voltage-dependent block of wild-type
      and mutant human ether-a-go-go related gene (HERG) K(+) channels by the
      antimalarial compound chloroquine. The block of wild-type HERG channels expressed
      in Xenopus oocytes was enhanced as the membrane potential was progressively
      depolarized. The IC(50) was 8.4 +/- 0.9 microm when assessed during 4-s voltage
      clamp pulses to 0 mV. Chloroquine also slowed the apparent rate of HERG
      deactivation, reflecting the inability of drug-bound channels to close. Mutation
      to alanine of aromatic residues (Tyr-652 or Phe-656) located in the S6 domain of
      HERG greatly reduced the potency of channel block by chloroquine (IC(50) > 1 mm
      at 0 mV). However, mutation of Tyr-652 also altered the voltage dependence of the
      block. In contrast to wild-type HERG, block of Y652A HERG channels was diminished
      by progressive membrane depolarization, and complete relief from block was
      observed at +40 mV. HERG channel block was voltage-independent when the hydroxyl
      group of Tyr-652 was removed by mutating the residue to Phe. Together these
      findings indicate a critical role for Tyr-652 in voltage-dependent block of HERG
      channels. Molecular modeling was used to define energy-minimized dockings of
      chloroquine to the central cavity of HERG. Our experimental findings and modeling
      suggest that chloroquine preferentially blocks open HERG channels by cation-pi
      and pi-stacking interactions with Tyr-652 and Phe-656 of multiple subunits.

PMID- 11960983
TI  - Respiratory detoxification of nitric oxide by the cytochrome c nitrite reductase
      of Escherichia coli.
AB  - Nitric oxide is a key element in host defense against invasive pathogens. The
      periplasmic cytochrome c nitrite reductase (NrfA) of Escherichia coli catalyzes
      the respiratory reduction of nitrite, but in vitro studies have shown that it can
      also reduce nitric oxide. The physiological significance of the latter reaction
      in vivo has never been assessed. In this study the reduction of nitric oxide by
      Escherichia coli was measured in strains active or deficient in periplasmic
      nitrite reduction. Nrf(+) cells, harvested from cultures grown anaerobically,
      possessed a nitric-oxide reductase activity with physiological electron donation
      of 60 nmol min(-1) x mg dry wt(-1), and an in vivo turnover number of NrfA of 390
      NO* s(-1) was calculated. Nitric-oxide reductase activity could not be detected
      in Nrf(-) strains. Comparison of the anaerobic growth of Nrf(+) and Nrf(-)
      strains revealed a higher sensitivity to nitric oxide in the NrfA(-) strains. A
      higher sensitivity to the nitrosating agent S-nitroso-N-acetyl penicillamine
      (SNAP) was also observed in agar plate disk-diffusion assays. Oxygen respiration
      by E. coli was also more sensitive to nitric oxide in the Nrf(-) strains compared
      with the Nrf(+) parent strain. The results demonstrate that active periplasmic
      cytochrome c nitrite reductase can confer the capacity for nitric oxide reduction
      and detoxification on E. coli. Genomic analysis of many pathogenic enteric
      bacteria reveals the presence of nrf genes. The present study raises the
      possibility that this reflects an important role for the cytochrome c nitrite
      reductase in nitric oxide management in oxygen-limited environments.

PMID- 11960984
TI  - Isolation and proteomic characterization of human Parvulin-associating
      preribosomal ribonucleoprotein complexes.
AB  - Human parvulin (hParvulin; Par14/EPVH) belongs to the third family of
      peptidylprolyl cis-trans isomerases that exhibit an enzymatic activity of
      interconverting the cis-trans conformation of the prolyl peptide bond, and shows
      sequence similarity to the regulator enzyme for cell cycle transitions, human
      Pin1. However, the cellular function of hParvulin is entirely unknown. Here, we
      demonstrate that hParvulin associates with the preribosomal ribonucleoprotein
      (pre-rRNP) complexes, which contain preribosomal RNAs, at least 26 ribosomal
      proteins, and 26 trans-acting factors involved in rRNA processing and assembly at
      an early stage of ribosome biogenesis. Since an amino-terminal domain of
      hParvulin, which is proposed to be a putative DNA-binding domain, was alone
      sufficient to associate in principle with the pre-rRNP complexes, the association
      is probably through protein-RNA interaction. In addition, hParvulin co
      precipitated at least 10 proteins not previously known to be involved in ribosome
      biogenesis. Coincidentally, most of these proteins are implicated in regulation
      of microtubule assembly or nucleolar reformation during the mitotic phase of the
      cell. Thus, these results, coupled with the preferential nuclear localization of
      hParvulin, suggest that hParvulin may be involved in ribosome biogenesis and/or
      nucleolar re-assembly of mammalian cells.

PMID- 11960985
TI  - Retinol/ethanol drug interaction during acute alcohol intoxication in mice
      involves inhibition of retinol metabolism to retinoic acid by alcohol
      dehydrogenase.
AB  - Substantial evidence indicates that one consequence of alcohol intoxication is a
      reduction in retinoic acid (RA) levels. Studies on the mechanism have shown that
      chronic ethanol consumption induces P450 enzymes that increase RA degradation,
      thus accounting for much but not all of the observed decrease in RA. A reduction
      in RA synthesis may also be involved as ethanol competitively inhibits retinol
      oxidation catalyzed by alcohol dehydrogenase (ADH) in vitro. This may be
      important during acute ethanol intoxication and may contribute to adverse
      retinol/ethanol drug interactions. Here we have examined mice for the effect of
      either acute ethanol intoxication or Adh1 gene disruption on RA synthesis and
      degradation. RA produced following a dose of retinol (50 mg/kg) was reduced 87%
      by pretreatment with an intoxicating dose of ethanol (3.5 g/kg). RA produced in
      Adh1-null mutant mice following a 50-mg/kg dose of retinol was reduced 82%
      relative to wild-type mice, thus similar to wild-type mice pretreated with
      ethanol. Reduced RA production was associated with increased retinol levels in
      both ethanol-treated wild-type mice and Adh1-null mutant mice, indicating reduced
      clearance of the retinol dose. RA degradation following a dose of RA (10 mg/kg)
      was increased only 42% by ethanol pretreatment (3.5 g/kg) and only 26% in Adh1
      null mutant mice relative to wild-type mice. These findings demonstrate that the
      reduced RA levels observed during acute retinol/ethanol drug interaction are due
      primarily to a decrease in ADH-catalyzed RA synthesis and secondarily to an
      increase in RA degradation.

PMID- 11960986
TI  - Structure of human chitotriosidase. Implications for specific inhibitor design
      and function of mammalian chitinase-like lectins.
AB  - Chitin hydrolases have been identified in a variety of organisms ranging from
      bacteria to eukaryotes. They have been proposed to be possible targets for the
      design of novel chemotherapeutics against human pathogens such as fungi and
      protozoan parasites as mammals were not thought to possess chitin-processing
      enzymes. Recently, a human chitotriosidase was described as a marker for Gaucher
      disease with plasma levels of the enzyme elevated up to 2 orders of magnitude.
      The chitotriosidase was shown to be active against colloidal chitin and is
      inhibited by the family 18 chitinase inhibitor allosamidin. Here, the crystal
      structure of the human chitotriosidase and complexes with a chitooligosaccharide
      and allosamidin are described. The structures reveal an elongated active site
      cleft, compatible with the binding of long chitin polymers, and explain the
      inactivation of the enzyme through an inherited genetic deficiency. Comparison
      with YM1 and HCgp-39 shows how the chitinase has evolved into these mammalian
      lectins by the mutation of key residues in the active site, tuning the substrate
      binding specificity. The soaking experiments with allosamidin and
      chitooligosaccharides give insight into ligand binding properties and allow the
      evaluation of differential binding and design of species-selective chitinase
      inhibitors.

PMID- 11960987
TI  - ATF4 is a mediator of the nutrient-sensing response pathway that activates the
      human asparagine synthetase gene.
AB  - Transcription from the asparagine synthetase (A.S.) gene is increased in response
      to either amino acid (amino acid response) or glucose (endoplasmic reticulum
      stress response) deprivation. These two independent pathways converge on the same
      set of genomic cis-elements within the A.S. promoter referred to as nutrient
      sensing response elements (NSRE) 1 and 2, both of which are necessary for gene
      activation. The NSRE-1 sequence was used to screen ATF/CREB family members by
      electrophoresis mobility shift assays and supershift by specific antibodies. The
      results indicated that ATF4 binds to the NSRE-1 sequence and that the amount of
      the ATF4 complex was increased when extracts from amino acid-deprived or glucose
      deprived cells were tested. Using electrophoresis mobility shift assay
      experiments and a probe that contained both NSRE-1 and NSRE-2, mutation of the
      NSRE-1 sequence completely prevented formation of the ATF4-containing complexes,
      whereas mutation of the NSRE-2 sequence did not. Overexpression of ATF4 increased
      A.S. promoter-driven transcription, whereas an inhibitory dominant negative ATF4
      mutant blocked both basal and starvation-enhanced transcription. Collectively,
      the results provide both in vitro and in vivo evidence for a role of ATF4 in the
      transcriptional activation of the A.S. gene in response to nutrient deprivation.

PMID- 11960988
TI  - Effect of the Streptococcus pneumoniae MmsA protein on the RecA protein-promoted
      three-strand exchange reaction. Implications for the mechanism of
      transformational recombination.
AB  - Streptococcus pneumoniae is a naturally transformable bacterium that is able to
      incorporate DNA from its environment into its own chromosome. This process, known
      as transformational recombination, is dependent in part on the mmsA gene, which
      encodes a protein having a sequence that is 40% identical to that of the
      Escherichia coli RecG protein, a junction-specific DNA helicase believed to be
      involved in the branch migration of recombinational intermediates. We have
      developed an expression system for the MmsA protein and have purified the MmsA
      protein to more than 99% homogeneity. The MmsA protein has DNA-dependent ATP
      hydrolysis and DNA junction-helicase activities that are similar to those of the
      E. coli RecG protein. The effect of the MmsA protein on the S. pneumoniae RecA
      protein-promoted three-strand exchange reaction was also investigated. In the
      standard direction (circular single-stranded (ss) DNA + linear double-stranded
      (ds) DNA --> linear ssDNA + nicked circular dsDNA), the MmsA protein appears to
      promote the branch migration of partially exchanged intermediates in a direction
      opposite of the RecA protein, resulting in a nearly complete inhibition of the
      overall strand exchange reaction. In the reverse direction (linear ssDNA + nicked
      circular dsDNA --> circular ssDNA + linear dsDNA), however, the MmsA protein
      appears to facilitate the conversion of partially exchanged intermediates into
      fully exchanged products, leading to a pronounced stimulation of the overall
      reaction. These results are discussed in terms of the molecular mechanism of
      transformational recombination.

PMID- 11960989
TI  - Structure and function of human erythrocyte pyruvate kinase. Molecular basis of
      nonspherocytic hemolytic anemia.
AB  - Deficiency of human erythrocyte isozyme (RPK) is, together with glucose-6
      phosphate dehydrogenase deficiency, the most common cause of the nonspherocytic
      hemolytic anemia. To provide a molecular framework to the disease, we have solved
      the 2.7 A resolution crystal structure of human RPK in complex with fructose 1,6
      bisphosphate, the allosteric activator, and phosphoglycolate, a substrate
      analogue, and we have functionally and structurally characterized eight mutants
      (G332S, G364D, T384M, D390N, R479H, R486W, R504L, and R532W) found in RPK
      deficient patients. The mutations target distinct regions of RPK structure,
      including domain interfaces and catalytic and allosteric sites. The mutations
      affect to a different extent thermostability, catalytic efficiency, and
      regulatory properties. These studies are the first to correlate the clinical
      symptoms with the molecular properties of the mutant enzymes. Mutations greatly
      impairing thermostability and/or activity are associated with severe anemia. Some
      mutant proteins exhibit moderate changes in the kinetic parameters, which are
      sufficient to cause mild to severe anemia, underlining the crucial role of RPK
      for erythrocyte metabolism. Prediction of the effects of mutations is difficult
      because there is no relation between the nature and location of the replaced
      amino acid and the type of molecular perturbation. Characterization of mutant
      proteins may serve as a valuable tool to assist with diagnosis and genetic
      counseling.

PMID- 11960990
TI  - Three camelid VHH domains in complex with porcine pancreatic alpha-amylase.
      Inhibition and versatility of binding topology.
AB  - Camelids produce functional antibodies devoid of light chains and CH1 domains.
      The antigen-binding fragment of such heavy chain antibodies is therefore
      comprised in one single domain, the camelid heavy chain antibody VH (VHH). Here
      we report on the structures of three dromedary VHH domains in complex with
      porcine pancreatic alpha-amylase. Two VHHs bound outside the catalytic site and
      did not inhibit or inhibited only partially the amylase activity. The third one,
      AMD9, interacted with the active site crevice and was a strong amylase inhibitor
      (K(i) = 10 nm). In contrast with complexes of other proteinaceous amylase
      inhibitors, amylase kept its native structure. The water-accessible surface areas
      of VHHs covered by amylase ranged between 850 and 1150 A(2), values similar to or
      even larger than those observed in the complexes between proteins and classical
      antibodies. These values could certainly be reached because a surprisingly high
      extent of framework residues are involved in the interactions of VHHs with
      amylase. The framework residues that participate in the antigen recognition
      represented 25-40% of the buried surface. The inhibitory interaction of AMD9
      involved mainly its complementarity-determining region (CDR) 2 loop, whereas the
      CDR3 loop was small and certainly did not protrude as it does in cAb-Lys3, a VHH
      inhibiting lysozyme. AMD9 inhibited amylase, although it was outside the direct
      reach of the catalytic residues; therefore it is to be expected that inhibiting
      VHHs might also be elicited against proteases. These results illustrate the
      versatility and efficiency of VHH domains as protein binders and enzyme
      inhibitors and are arguments in favor of their use as drugs against diabetes.

PMID- 11960992
TI  - Biochemical properties of purified recombinant human beta-carotene 15,15'
      monooxygenase.
AB  - Beta-carotene 15,15'-monooxygenase (BCO), formerly known as beta-carotene 15,15'
      dioxygenase, catalyzes the first step in the synthesis of vitamin A from dietary
      carotenoids. We have biochemically and enzymologically characterized the purified
      recombinant human BCO enzyme. A highly active BCO enzyme was expressed and
      purified to homogeneity from baculovirus-infected Spodoptera frugiperda 9 insect
      cells. The K(m) and V(max) of the enzyme for beta-carotene were 7 microm and 10
      nmol retinal/mg x min, respectively, values that corresponded to a turnover
      number (k(cat)) of 0.66 min(-1) and a catalytic efficiency (k(cat)/K(m)) of
      approximately 10(5) m(-1) x min(-1). The enzyme existed as a tetramer in
      solution, and substrate specificity analyses suggested that at least one
      unsubstituted beta-ionone ring half-site was imperative for efficient cleavage of
      the carbon 15,15'-double bond in carotenoid substrates. High levels of BCO mRNA
      were observed along the whole intestinal tract, in the liver, and in the kidney,
      whereas lower levels were present in the prostate, testis, ovary, and skeletal
      muscle. The current data suggest that the human BCO enzyme may, in addition to
      its well established role in the digestive system, also play a role in peripheral
      vitamin A synthesis from plasma-borne provitamin A carotenoids.

PMID- 11960991
TI  - Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells.
      A role for HER2 AND PKC-delta.
AB  - Activation of mitogen-activated protein kinase (Erk/MAPK) is a critical signal
      transduction event for estrogen (E(2))-mediated cell proliferation. Recent
      studies from our group and others have shown that persistent activation of Erk
      plays a major role in cell migration and tumor progression. The signaling
      mechanism(s) responsible for persistent Erk activation are not fully
      characterized, however. In this study, we have shown that E(2) induces a slow but
      persistent activation of Erk in MCF-7 breast carcinoma cells. The E(2)-induced
      Erk activation is dependent on new protein synthesis, suggesting that E(2)
      induced growth factors play a major role in Erk activation. When MCF-7 cells were
      treated with E(2) in the presence of an anti-HER-2 monoclonal antibody
      (herceptin), 60-70% of E(2)-induced Erk activation is blocked. In addition, when
      untreated MCF-7 cells were exposed to conditioned medium from E(2)-treated cells,
      Erk activity was significantly enhanced. Furthermore Erk activity was blocked by
      an antibody against HER-2 or by heregulin (HRG) depletion from the conditioned
      medium through immunoprecipitation. In contrast, epidermal growth factor receptor
      (Ab528) antibody only blocked 10-20% of E(2)-induced Erk activation, suggesting
      that E(2)-induced Erk activation is predominantly mediated through the secretion
      of HRG and activation of HER-2 by an autoctine/paracrine mechanism. Inhibition of
      PKC-delta-mediated signaling by a dominant negative mutant or the relatively
      specific PKC-delta inhibitor rottlerin blocked most of the E(2)-induced Erk
      activation but had no effect on TGF alpha-induced Erk activation. By contrast
      inhibition of Ras, by inhibition of farnesyl transferase (Ftase-1) or dominant
      negative (N17)-Ras, significantly inhibited both E(2)- and TGF alpha-induced Erk
      activation. This evaluation of downstream signaling revealed that E(2)-induced
      Erk activation is mediated by a HRG/HER-2/PKC-delta/Ras pathway that could be
      crucial for E(2)-dependent growth-promoting effects in early stages of tumor
      progression.

PMID- 11960993
TI  - An endogenous Drosophila receptor for glycans bearing alpha 1,3-linked core
      fucose residues.
AB  - The genome of Drosophila melanogaster encodes several proteins that are predicted
      to contain Ca(2+)-dependent, C-type carbohydrate-recognition domains. The CG2958
      gene encodes a protein containing 359 amino acid residues. Analysis of the CG2958
      sequence suggests that it consists of an N-terminal domain found in other
      Drosophila proteins, a middle segment that is unique, and a C-terminal C-type
      carbohydrate-recognition domain. Expression studies show that the full-length
      protein is a tetramer formed by noncovalent association of disulfide-linked
      dimers that are linked through cysteine residues in the N-terminal domain. The
      expressed protein binds to immobilized yeast invertase through the C-terminal
      carbohydrate-recognition domain. Competition binding studies using
      monosaccharides demonstrate that CG2958 interacts specifically with fucose and
      mannose. Fucose binds approximately 5-fold better than mannose. Blotting studies
      reveal that the best glycoprotein ligands are those that contain N-linked glycans
      bearing alpha1,3-linked fucose residues. Binding is enhanced by the additional
      presence of alpha1,6-linked fucose. It has previously been proposed that labeling
      of the Drosophila neural system by anti-horseradish peroxidase antibodies is a
      result of the presence of difucosylated N-linked glycans. CG2958 is a potential
      endogenous receptor for such neural-specific carbohydrate epitopes.

PMID- 11960994
TI  - Methyl-CpG binding domain protein 2 represses transcription from hypermethylated
      pi-class glutathione S-transferase gene promoters in hepatocellular carcinoma
      cells.
AB  - During the pathogenesis of human hepatocellular carcinoma (HCC), the CpG island
      encompassing the pi-class glutathione S-transferase gene (GSTP1) becomes
      hypermethylated. Repression of transcription accompanying CpG island
      hypermethylation has been proposed to be mediated by methyl-CpG binding domain
      (MBD) proteins. We report here that inhibition of transcription from
      hypermethylated GSTP1 promoters in Hep3B HCC cells, which fail to express GSTP1
      mRNA or GSTP1 polypeptides, appears to be mediated by MBD2. Treatment of Hep3B
      cells with 5-azadeoxycytidine (5-aza-dC), a methyltransferase inhibitor,
      activated GSTP1 expression, whereas treatment with trichostatin A, a histone
      deacetylase inhibitor, had little effect. To more precisely assess the
      contribution of the pattern of GSTP1 CpG island methylation on GSTP1 mRNA
      expression, Hep3B cells were treated for 72 h with 5-aza-dC and then subjected to
      limiting dilution cloning. Bisulfite sequencing was used to map the methylation
      patterns of the GSTP1 promoter region in GSTP1-expressing and -non-expressing
      clones. In the clone that expressed GSTP1 mRNA determined by Northern blot
      analysis and quantitative reverse transcriptase (RT)-PCR, widespread
      demethylation of at least one GSTP1 allele was evident. Chromatin
      immunoprecipitation experiments revealed the presence of MBD2, but not Sp1, at
      the GSTP1 promoter in Hep3B cells. In contrast, Sp1 was detected at the GSTP1
      promoter in a GSTP1-expressing Hep3B 5-aza-dC subclone. To test whether MBD2
      might be responsible for the inhibition of GSTP1 transcription from
      hypermethylated GSTP1 promoters, siRNAs were used to reduce MBD2 polypeptide
      levels in Hep3B cells. SssI-catalyzed methylation of GSTP1 promoter sequences
      resulted in diminished luciferase reporter activity after transfection into Hep3B
      cells. However, when hypermethylated GSTP1 promoter sequences were transfected
      into Hep3B cells that had been treated with siRNA-targeting MBD2 mRNA, no
      repression of luciferase reporter expression was evident. These findings
      implicate MBD2 in the repression of GSTP1 expression associated with GSTP1 CpG
      island hypermethylation in HCC cells.

PMID- 11960995
TI  - Escherichia coli apurinic-apyrimidinic endonucleases enhance the turnover of the
      adenine glycosylase MutY with G:A substrates.
AB  - The DNA repair enzyme MutY plays an important role in the prevention of DNA
      mutations resulting from the presence of the oxidatively damaged lesion 7,8
      dihydro-8-oxo-2'-deoxyguanosine (OG). MutY is a base excision repair (BER)
      glycosylase that removes misincorporated adenine residues from OG:A mispairs, as
      well as G:A and C:A mispairs. We have previously shown that, under conditions of
      low MutY concentrations relative to an OG:A or G:A substrate, the time course of
      the adenine glycosylase reaction exhibits biphasic kinetic behavior due to slow
      release of the DNA product by MutY. The dissociation of MutY from its product may
      require the recruitment of other proteins from the BER pathway, such as an
      apurinic-apyrimidinic (AP) endonuclease, as turnover-enhancing cofactors. The
      effect of the AP endonucleases endonuclease IV (Endo IV), exonuclease III (Exo
      III), and Ape1 on the reaction kinetics of MutY with G:A- and OG:A-containing
      substrates was investigated. The effect of the glycosylases UDG and MutM and the
      DNA polymerase pol I was also characterized. Endo IV and Exo III, unlike Ape1,
      UDG, and pol I, greatly enhance the rate of product release with a G:A substrate,
      whereas the rate constant for the adenine removal step remains unchanged.
      Furthermore, the turnover rate with a truncated form of MutY, Stop 225, which
      lacks 125 amino acids of the C terminus, is unaffected by the presence of Endo IV
      or Exo III. These results constitute the first evidence of an interaction between
      the MutY-product DNA complex and Endo IV or Exo III. Furthermore, they suggest a
      role for the C-terminal domain of MutY in mediating this interaction.

PMID- 11960996
TI  - An N-terminal truncated form of Orp150 is a cytoplasmic ligand for the anti
      proliferative mushroom Agaricus bisporus lectin and is required for nuclear
      localization sequence-dependent nuclear protein import.
AB  - Nuclear localization sequence-dependent nuclear protein import is essential for
      maintaining cell function and can be selectively blocked in epithelial cells by
      mushroom (Agaricus bisporus) lectin. Here we report that a major intracellular
      ligand for this lectin is an N-terminally truncated form of oxygen-regulated
      protein 150 (Orp150), which lacks the endoplasmic reticulum translocation signal
      peptide of full-length Orp150. This cytoplasmic form of Orp150 expresses the
      lectin carbohydrate ligand (sialyl-2,3-galactosyl-beta1,3-N-acetylgalactosamine
      alpha) and is shown to be essential for nuclear localization sequence-dependent
      nuclear protein import.

PMID- 11960997
TI  - SUMO-1 modification of histone deacetylase 1 (HDAC1) modulates its biological
      activities.
AB  - Histone deacetylation plays a central role in the regulation of genes linked to
      virtually all biological processes. This modification reaction is dependent on a
      family of related histone deacetylases (HDACs), which function as key components
      of large multiprotein complexes involved in the development of normal and
      neoplastic cells. The mechanisms regulating HDACs and their roles in such
      processes are not understood, and these form the major focus for the current
      study. Here, in the course of assessing possible post-translational modifications
      of HDAC1, we demonstrated that HDAC1 is a substrate for SUMO-1 (small ubiquitin
      related modifier) modification in vitro and in vivo. The HDAC1 lysines targeted
      for modification were identified as C-terminal Lys-444 and Lys-476, which are
      also present in mammalian HDAC2 and lower vertebrate HDAC1/2 orthologs yet absent
      from other HDAC family members, pointing to a means of differential regulation
      among HDAC proteins. Mutation of these target residues (lysine to arginine
      substitution) profoundly reduced HDAC1-mediated transcriptional repression in
      reporter assays without affecting HDAC1 ability to associate with mSin3A and
      eliminated HDAC1-induced cell cycle and apoptotic responses upon overexpression.
      Together, the results demonstrate that HDAC1 is modified by SUMO-1, and this
      modification can dramatically affect HDAC1 activity in a number of surrogate
      biological assays.

PMID- 11960998
TI  - The first years of the Journal of Biological Chemistry.

PMID- 11960999
TI  - Angiotensin II directly stimulates ENaC activity in the cortical collecting duct
      via AT(1) receptors.
AB  - Angiotensin II (AngII) helps to regulate overall renal tubular reabsorption of
      salt and water, yet its effects in the distal nephron have not been well studied.
      The purpose of these studies was to determine whether AngII stimulates luminal
      Na(+) transport in the cortical collecting duct (CCD). Intracellular Na(+)
      concentration ([Na(+)](i)), as a reflection of Na(+) transport across the apical
      membrane, was measured with fluorescence microscopy using sodium-binding
      benzofuran isophthalate (SBFI) in isolated, perfused CCD segments dissected from
      rabbit kidneys. Control [Na(+)](i), during perfusion with 25 mM NaCl and a Na(+)
      free solution in the bath containing the Na(+)-ionophore monensin (10 microM, to
      eliminate basolateral membrane Na(+) transport) averaged 19.3 +/- 5.2 mM (n =
      16). Increasing luminal [NaCl] to 150 mM elevated [Na(+)](i) by 9.87 +/- 1.5 mM
      (n = 7; P < 0.05). AngII (10(-9) M) added to the lumen significantly elevated
      baseline [Na(+)](i) by 6.3 +/- 1.0 mM and increased the magnitude (Delta = 25.2
      +/- 3.7 mM) and initial rate ( approximately 5 fold) of change in [Na(+)](i) to
      increased luminal [NaCl]. AngII when added to the bath had similar stimulatory
      effects; however, AngII was much more effective from the lumen. Thus, AngII
      significantly increased the apical entry of Na(+) in the CCD. To determine if
      this apical entry step occurred via the epithelial Na(+) channel (ENaC), studies
      were performed using the specific ENaC blocker, benzamil hydrochloride (10(-6)
      M). When added to the perfusate, benzamil almost completely inhibited the
      elevations in [Na(+)](i) to increased luminal [NaCl] in both the presence and
      absence of AngII. These results suggest that AngII directly stimulates Na(+)
      channel activity in the CCD. AT(1) receptor blockade with candesartan or losartan
      (10(-6) M) prevented the stimulatory effects of AngII. Regulation of ENaC
      activity by AngII may play an important role in distal Na(+) reabsorption in
      health and disease.

PMID- 11961000
TI  - Low tonicity mediates a downregulation of cyclooxygenase-1 expression by
      furosemide in the rat renal papilla.
AB  - It is well known that loop diuretics enhance the renal excretion of prostanoids;
      therefore, this study aimed to characterize the influence of loop diuretics on
      the intrarenal expression of cyclooxygenases, which are the key enzymes for
      prostanoid formation. Male Sprague-Dawley rats were infused with furosemide (12
      mg/kg per d) for 6 d, and the expression of cyclooxygenase-1 and -2 (Cox-1 and
      Cox-2) was analyzed in the different kidney zones. Furosemide increased Cox-2
      mRNA expression approximately twofold in the cortex, but it left Cox-1 mRNA
      expression unaltered there. In the outer medulla, furosemide changed neither Cox
      1 nor Cox-2 mRNA expression. In the inner medulla, however, furosemide decreased
      Cox-1 and Cox-2 mRNA levels to approximately 30% and 60% of their control levels,
      respectively. The downregulation of mRNA was paralleled by a decrease of Cox
      protein in the collecting ducts and interstitial cells. Moreover, tissue
      prostaglandin E(2) (PGE(2)) concentrations in the papilla were markedly decreased
      by furosemide to about 30% of the control level. Furosemide lowered urine
      osmolality from 1550 mosmol/kg to 480 mosmol/kg; therefore, further consideration
      was given to the influence of tonicity as a possible mediator of the effects of
      furosemide on the Cox expression. Water loading was therefore used to reduce the
      medullary tonicity by a second maneuver. Water loading led to a similar reduction
      in papillary Cox mRNA expression and PGE(2) content like furosemide. To
      investigate the influence of the osmolarity on the expression of Cox and the
      production of PGE(2) under defined in vitro conditions, inner medullary
      collecting duct cells were incubated with culture medium containing graded
      amounts of NaCl ranging from 200 mmol/L to 600 mmol/L, and Cox-1 and Cox-2 mRNA
      abundance were determined after 24 h an 48 h. Cox-1 and Cox-2 mRNA abundance
      changed in parallel with the osmolarity. The data suggest that loop diuretics
      decrease the expression of cyclooxygenases and consequently tissue PGE(2)
      concentrations in the kidney inner medulla. This effect could be related to the
      breakdown of the papillary osmotic gradient induced by loop diuretics.

PMID- 11961001
TI  - Purinergic receptor signaling at the basolateral membrane of macula densa cells.
AB  - Purinergic receptors are important in the regulation of renal hemodynamics;
      therefore, this study sought to determine if such receptors influence macula
      densa cell function. Isolated glomeruli containing macula densa cells, with and
      without the cortical thick ascending limb, were loaded with the Ca(2+) sensitive
      indicators, Fura Red (confocal microscopy) or fura 2 (conventional video image
      analysis). Studies were performed on an inverted microscope in a chamber with a
      flow-through perfusion system. Changes in cytosolic calcium concentration
      ([Ca(2+)](i)) from exposed macula densa plaques were assessed upon addition of
      adenosine, ATP, UTP, ADP, or 2-methylthio-ATP (2- MeS-ATP) for 2 min added to the
      bathing solution. There was no change in [Ca(2+)](i) with addition of adenosine
      (10(-7) to 10(-3) M). UTP and ATP (10(-4) M) caused [Ca(2+)](i) to increase by
      268 +/- 40 nM (n = 21) and 295 +/- 53 nM (n = 21), respectively, whereas in
      response to 2MesATP and ADP, [Ca(2+)](i) increased by only 67 +/- 13 nM (n = 8)
      and 93 +/- 36 nM (n = 14), respectively. Dose response curve for ATP (10(-7) to
      10(-3) M) added in bath showed an EC(50) of 15 microM. No effect on macula densa
      [Ca(2+)](i) was seen when ATP was added from the lumen. ATP caused similar
      increases in macula densa [Ca(2+)](i) in the presence or absence of bath Ca(2+)
      and addition of 5 mM ethyleneglycotetraacetic acid (EGTA). Suramin (an antagonist
      of P2X and P2Y receptors) completely inhibited ATP-induced [Ca(2+)](i) dynamics.
      Also, ATP-Ca(2+) responsiveness was prevented by the phospholipase C inhibitor, U
      73122, but not by its inactive analog, U-73343. These results suggest that macula
      densa cells possess P2Y(2) purinergic receptors on basolateral but not apical
      membranes and that activation of these receptors results in the mobilization of
      Ca(2+).

PMID- 11961002
TI  - ATP depletion of tubular cells causes dissociation of the zonula adherens and
      nuclear translocation of beta-catenin and LEF-1.
AB  - This study examined the events associated with the reversible disruption of the
      structural and functional integrity of the zonula occludens (ZA) induced by ATP
      depletion of renal tubular cells. It shows that loss of the ZA after ATP
      depletion is associated with the withdrawal of E-cadherin, alpha-catenin, and
      beta-catenin, probably as intact cadherin-catenin complexes from the basolateral
      membrane of tubular cells. The relative amounts of all three proteins increased
      in the Triton X-100-insoluble fraction of cell lysates and decreased in the
      Triton X-100-soluble pool. These changes were reversed with repletion of cell
      ATP. It is additionally shown that ATP depletion induces nuclear translocation of
      beta-catenin and T cell factor (TCF)/lymphoid enhancer factor-1 (LEF-1), a
      transcriptional factor with which beta-catenin associates. The redistribution of
      the ZA proteins as intact E-cadherin-catenin complexes from the plasma membrane
      facilitates the rapid recovery of the ZA after sublethal ischemic injury. The
      translocation of beta-catenin and TCF/LEF-1 to the nucleus indicates that ATP
      depletion may activate the wnt/wingless signal transduction pathway. Thus,
      entirely novel evidence is provided that both of the known roles of beta-catenin,
      as a structural part of the ZA and as a component of the wnt/wingless pathway,
      play a role after sublethal ischemic injury to tubular cells. It is also
      speculated that the nuclear translocation of beta-catenin and TCF/LEF-1 modulates
      gene expression after ischemic injury and may contribute to events necessary for
      renal regeneration and repair after ischemic injury.

PMID- 11961003
TI  - Angiotensin III activates nuclear transcription factor-kappaB in cultured
      mesangial cells mainly via AT(2) receptors: studies with AT(1) receptor-knockout
      mice.
AB  - Nuclear factor-kappaB (NF-kappaB) regulates many genes involved in renal
      pathophysiologic processes. It was previously demonstrated that angiotensin II
      (AngII) and its amino-terminal degradation product AngIII activate NF-kappaB in
      mesangial cells. However, which are the Ang receptor subtypes involved in the NF
      kappaB pathway and whether these Ang peptides act through the same or different
      receptors in mesangial cells have not been evaluated. Under the culture
      conditions used, quiescent rat mesangial cells expressed both AT(1) and AT(2)
      receptors. To investigate the receptors involved in the NF-kappaB pathway, two
      different approaches were used, i.e., pharmacologic studies, using specific AT(1)
      and AT(2) receptor antagonists and agonists, and studies in AT(1) receptor
      knockout mice. In cultured rat mesangial cells, both AT(1) and AT(2) receptor
      antagonists inhibited AngII-induced NF-kappaB DNA binding activity, whereas NF
      kappaB activation elicited by AngIII was mainly blocked by the AT(2) receptor
      antagonist. Similar results were observed for cytosolic IkappaBalpha degradation.
      An AT(2) receptor agonist also activated NF-kappaB. In AT(1) receptor-knockout
      murine mesangial cells, AngIII and AngII increased NF-kappaB activity and
      degraded cytosolic IkappaBalpha; both processes were blocked by the AT(2)
      receptor antagonist. These data demonstrate that, in mesangial cells, NF-kappaB
      activation is mediated by AT(1) and AT(2) receptors, suggesting a novel
      intracellular signaling mechanism for AT(2) receptors in the kidney. Some
      differences in Ang peptide receptor-mediated responses were also observed. AngII
      activates NF-kappaB via AT(1) and AT(2) receptors, whereas AngIII acts mainly via
      AT(2) receptors. These results suggest the potential involvement of the
      AngIII/AT(2) receptor/NF-kappaB pathway in pathophysiologic processes in the
      kidney and provide a better understanding of the renin-angiotensin system.

PMID- 11961004
TI  - The hypertrophic effect of transforming growth factor-beta is reduced in the
      absence of cyclin-dependent kinase-inhibitors p21 and p27.
AB  - Transforming growth factor-beta (TGF-beta) has both antiproliferative and
      hypertrophic effects on mesangial cells (MC). However, it is not known if these
      processes are independent or if they share common signaling pathways.
      Proliferation and hypertrophy are regulated by specific cell-cycle regulatory
      proteins, where the cyclin-dependent kinase (CDK) inhibitors inhibit target
      cyclin-CDK complexes. This study examined whether the growth regulatory effects
      of TGF-beta were determined by the CDK inhibitors p21 and p27. Accordingly,
      cultured MC from wild type (+/+) and single and double null (-/-) p21 and p27
      mice were grown in 5% serum in the presence or absence of TGF-beta1 (2 ng/ml).
      Proliferation ([(3)H]-thymidine incorporation, cell number, cell cycle) and
      hypertrophy ([(3)H]-leucine incorporation, total protein content, forward light
      scatter) were measured after 24 h, 48 h, and 96 h. TGF-beta inhibited
      proliferation in +/+ and p21/p27 double -/- MC to a similar extent. TGF-beta
      induced hypertrophy in +/+ MC (18.0% increase at 48 h), and to lesser extent in
      p21 -/- (12.8%) and p27 -/- MC (11.5%) measured by forward light scatter
      analysis. In p21/p27 double -/-, the hypertrophic effects of TGF-beta were
      significantly reduced (3.9% at 48 h). Similar results were obtained by measuring
      hypertrophy by total protein and [(3)H]-leucine incorporation. In conclusion, the
      CDK inhibitors p21 and p27 are not required for the antiproliferative effects of
      TGF-beta. However, the hypertrophic growth effects of TGF-beta are reduced in the
      absence of both p21 and p27. These data suggest that the regulation of the
      antiproliferative and hypertrophic effects of TGF-beta may be distinct processes.

PMID- 11961005
TI  - Protein overload-induced NF-kappaB activation in proximal tubular cells requires
      H(2)O(2) through a PKC-dependent pathway.
AB  - Abnormal traffic of proteins through the glomerular capillary has an intrinsic
      toxicity that results in tubular dysfunction and interstitial inflammation. It
      has been previously shown that in porcine proximal tubular cells high
      concentrations of albumin activated NF-kappaB, which is responsible for the
      enhanced synthesis of the inflammatory chemokine RANTES. This study investigates
      whether reactive oxygen species (ROS) served as second messengers in protein
      overload-induced NF-kappaB activation. Human proximal tubular cells (HK-2) were
      incubated (5 to 60 min) with human albumin and IgG (1 to 30 mg/ml). Both proteins
      induced a rapid or significant increase in hydrogen peroxide (H(2)O(2))
      production at 5 min and persisting at 60 min. This effect was dose-dependent. The
      contribution of H(2)O(2) in regulating NF-kappaB activation was evaluated by
      using the antioxidants dimethyl-thiourea and pyrrolidine dithiocarbamate in
      protein-overloaded HK-2 cells. Both agents, by preventing H(2)O(2) generation,
      induced human albumin or IgG inhibited NF-kappaB activation. Stimulation of HK-2
      with exogenous H(2)O(2) resulted in the activation of a NF-kappaB subunit pattern
      similar to that obtained after protein challenge. Specific inhibitors of protein
      kinase C (PKC) activity significantly prevented H(2)O(2) production and
      consequent NF-kappaB activation, suggesting that ROS generation in HK-2 cells
      occurs downstream of PKC activation. Either antioxidants or PKC inhibitor almost
      completely abolished the upregulation of the monocyte chemoattractant protein-1
      gene induced by excess albumin, as evaluated by real-time PCR, thus supporting a
      role for PKC and ROS as critical signals for the expression of NF-kappaB
      dependent inflammatory genes. To identify the enzymatic sources responsible for
      the increased H(2)O(2) production, the effect of dyphenyleneiodonium, an
      inhibitor of the membrane NADP(H) oxidase, was studied, as was the effect of
      rotenone, which blocks complex I of the mitochondrial respiratory chain. It was
      found that both agents significantly reduced the exaggerated H(2)O(2) induced by
      protein overload. These data indicate that exposure to excess proteins in
      proximal tubular cells induces the formation of ROS, which are responsible for NF
      kappaB activation and consequent induction of NF-kappaB-dependent inflammatory
      signals.

PMID- 11961006
TI  - Sgk1 gene expression in kidney and its regulation by aldosterone: spatio-temporal
      heterogeneity and quantitative analysis.
AB  - The serine-threonine kinase sgk1 was recently identified as a gene rapidly
      induced by mineralocorticoids, resulting in increased sodium transport in vitro.
      To carefully localize and quantify the renal sgk1 expression response to
      aldosterone, in situ hybridization was performed on kidneys of mice having
      aldosterone excess over a range of doses and durations. In control and
      adrenalectomized animals, the glomeruli and inner medullary collecting ducts were
      the major sites of sgk1 expression, which was maintained independent of
      aldosterone. Sgk1 upregulation induced by aldosterone excess exhibited spatio
      temporal heterogeneity. Both acute (3-h) and chronic (6-d) aldosterone excess
      stimulated sgk1 expression in the distal nephron, i.e., from the distal
      convoluted tubules through to the outer medullary collecting ducts. Treatments
      for 6 d with low sodium diet (0.03% [I]) and aldosterone infusions (50 microg/kg
      per d [II], 150 microg/kg per d [III], and 750 microg/kg per d [IV]) generated
      elevation of circulating aldosterone. Across these treatments (I through IV), the
      circulating level correlated with the progressive induction of sgk1 expression,
      with highly stimulated tubules first appearing in cortex (I) and continuing
      downward (II) until there was a strong stimulation throughout outer medulla (III
      and IV). Interestingly, chronic but not acute aldosterone excess caused a slight
      increase of sgk1 expression in glomerulus (30 to 50%; P < 0.01) and a dramatic
      downregulation in the initial portion of inner medulla, which could result from
      diminished interstitial osmolarity. Relative quantification (versus control) of
      sgk1 upregulation in individual tubules revealed: (1) a 1.8-fold increase of sgk1
      mRNA at 3 h (150 microg/kg injection) and (2) a dose-dependence of chronic
      upregulation reaching a ceiling of eightfold elevation.

PMID- 11961007
TI  - Transcription factor IRF-1 in kidney transplants mediates resistance to graft
      necrosis during rejection.
AB  - In many circumstances kidney transplants remain viable despite extensive
      inflammation, permitting rejection episodes to be reversed. The mechanisms by
      which the kidney resists host effector mechanisms are not known. In mouse kidney
      transplants, resistance requires interferon-gamma (IFN-gamma), which acts on the
      graft to protect the graft from necrosis during the first days of rejection as
      well as inducing major histocompatibility complex (MHC) expression. Because some
      effects of IFN-gamma are mediated by transcription factor IRF-1, the role of IRF
      1 in the donor tissue early phases of rejection of mouse kidney allografts was
      studied. H-2(b) kidneys were transplanted from mice with wild-type IRF-1 genes
      (WT) or mice with disrupted IRF-1 genes (IRF-1KO) into CBA (H-2(k)) recipients.
      At day 5 and day 7, IRF-1KO and WT kidneys were functioning despite typical
      rejection pathology: interstitial infiltration and tubulitis. However, function
      deteriorated rapidly in rejecting IRF-1KO allografts, associated with widespread
      epithelial necrosis, peritubular capillary congestion, glomerulitis, and fibrin
      thrombi in small veins by day 7. At day 21, WT kidneys were viable despite severe
      tubulitis and arteritis, whereas IRF-1KO kidneys showed massive necrosis of the
      epithelium despite patent large vessels. Compared with WT kidneys, rejecting IRF
      1KO kidneys showed less induction of donor MHC yet had similar mRNA levels of
      perforin, granzyme B, and Fas ligand and evoked host alloantibody responses. Thus
      in rejecting kidney transplants, IRF-1 in the graft mediates MHC induction, but
      it also mediates resistance to necrosis, an effect that could be crucial to
      permit success in interventions against rejection.

PMID- 11961008
TI  - Osteopontin synthesis and localization along the human nephron.
AB  - In normal human and rat kidneys, osteopontin (OPN) is present at the apical
      surface of cells in the distal nephron. After ischemic or toxic renal damage in
      rats, OPN is upregulated in distal tubular cells (DTC) and expressed de novo in
      perinuclear vesicles in proximal tubular cells (PTC). In the first phase of this
      study, OPN localization in ischemic human biopsies was compared with that in
      ischemic rat kidneys. In the second phase, cultures of PTC and DTC were used to
      investigate human renal OPN synthesis, secretion, and localization. OPN
      localization in human biopsies after renal ischemia was comparable to that in
      ischemic rat kidneys. Microscopic and flow cytometric detection of
      immunofluorescent OPN staining in tubular cell cultures demonstrated strong
      plasma membrane localization in DTC, whereas mainly perinuclear intracellular
      expression was observed in PTC. Northern blotting and reverse transcription-PCR
      demonstrated production of a single OPN mRNA in PTC and DTC. Detection of OPN by
      Western blotting and enzyme-linked immunosorbent assay demonstrated that PTC and
      DTC synthesized and secreted the same three molecular mass OPN forms, in
      comparable amounts. Finally, confocal microscopy demonstrated different staining
      patterns for endocytotic/lysosomal vesicles and perinuclear OPN; however,
      perinuclear OPN exhibited colocalization with the Golgi apparatus. In conclusion,
      human renal OPN localization in cell cultures demonstrated differences between
      PTC and DTC comparable to those observed after renal ischemia in vivo. Therefore,
      these cell cultures represented an excellent model for the study of human OPN
      synthesis, secretion, and localization in PTC versus DTC. It is reported for the
      first time that intracellular OPN is located in the Golgi apparatus of both PTC
      and DTC and that PTC and DTC are able to produce and secrete the same OPN
      isoforms, in comparable amounts.

PMID- 11961009
TI  - Mesangial cell-binding anti-DNA antibodies in patients with systemic lupus
      erythematosus.
AB  - The mechanisms by which anti-DNA antibodies contribute to the pathogenesis of
      lupus nephritis (LN) remain to be elucidated. This study investigates the binding
      of polyclonal anti-DNA immunoglobulins from patients with systemic lupus
      erythematosus (SLE) to human mesangial cells (HMC) in vitro. Testing of cross
      sectional serum samples from 280 LN patients (108 during active disease; 172
      during remission), 35 SLE patients without renal involvement, 72 patients with
      non-lupus primary glomerular diseases, and 37 healthy subjects with a cellular
      enzyme-linked immunosorbent assay showed significant IgG mesangial cell-binding
      activity in patients with SLE, particularly those with active LN (P < 0.0001).
      Significant HMC-binding activity was demonstrated in 83.9%, 42.8%, and 47.1% of
      patients with active LN, inactive LN, and non-renal SLE, respectively. This was
      predominantly attributed to binding by anti-DNA antibodies, and immune complex
      binding accounted for 4.6%, 3.5%, and 2.8% of seropositive samples in the
      respective groups. Longitudinal studies in 27 LN patients demonstrated
      correlation between serial levels of anti-DNA antibodies, serum HMC-binding
      activity, and disease activity in 18 patients (66.7%). Affinity-purified
      polyclonal IgG anti-DNA antibodies from sera with HMC-binding activity showed
      significant binding to cultured HMC, and to a lesser extent glomerular and
      proximal tubular epithelial cells and human umbilical vein endothelial cells, but
      not tumor cell lines, peritoneal mesothelial cells, bronchial epithelial cells,
      or fibroblasts. The binding of anti-DNA antibodies to HMC was increased 1.47-fold
      (P = 0.0059) after the removal of Ig-associated DNA by DNase treatment, but it
      was unaffected by DNase treatment of HMC membrane. Controlled trypsinization of
      membrane proteins in HMC resulted in a 1.26-fold (P = 0.0025) increase in their
      binding by anti-DNA antibodies. In conclusion, subsets of anti-DNA antibodies
      from patients with SLE are capable of binding to HMC. The association of such
      binding with renal involvement and disease activity and its modulation by DNA
      concentration suggest that Ig binding to HMC can be a potential marker for
      disease activity in selected patients and that the binding of anti-DNA antibodies
      to HMC may be a pathogenetic mechanism in LN.

PMID- 11961010
TI  - The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates
      with the severity of renal disease.
AB  - The severity of renal cystic disease in the major form of autosomal dominant
      polycystic kidney disease (PKD1) is highly variable. Clinical data was analyzed
      from 324 mutation-characterized PKD1 patients (80 families) to document factors
      associated with the renal outcome. The mean age to end-stage renal disease (ESRD)
      was 54 yr, with no significant difference between men and women and no
      association with the angiotensin-converting enzyme polymorphism. Considerable
      intrafamilial variability was observed, reflecting the influences of genetic
      modifiers and environmental factors. However, significant differences in outcome
      were also found among families, with rare examples of unusually late-onset PKD1.
      Possible phenotype/genotype correlations were evaluated by estimating the effects
      of covariants on the time to ESRD using proportional hazards models. In the total
      population, the location of the mutation (in relation to the median position;
      nucleotide 7812), but not the type, was associated with the age at onset of ESRD.
      Patients with mutations in the 5' region had significantly more severe disease
      than the 3' group; median time to ESRD was 53 and 56 yr, respectively (P =
      0.025), with less than half the chance of adequate renal function at 60 yr (18.9%
      and 39.7%, respectively). This study has shown that the position of the PKD1
      mutation is significantly associated with earlier ESRD and questions whether PKD1
      mutations simply inactivate all products of the gene.

PMID- 11961011
TI  - A novel approach to investigation of the pathogenesis of active minimal-change
      nephrotic syndrome using subtracted cDNA library screening.
AB  - Clinical and experimental observations suggest that minimal-change nephrotic
      syndrome (MCNS) results from T cell dysfunction, via unknown mechanisms. For the
      identification of genes that are potentially involved in MCNS, a subtractive cDNA
      library was constructed from cDNA from T cell-enriched peripheral blood
      mononuclear cells obtained from the same patient during relapse versus remission
      ("relapse minus remission"). This library was screened by differential
      hybridization with forward ("relapse minus remission") and reverse ("remission
      minus relapse") subtractive cDNAs probes, as well as unsubtracted probes from
      relapse and remission, and irrelevant nephrotic syndrome (membranous
      nephropathy). A total of 84 transcripts were isolated, of which 12 matched
      proteins of unknown function and 30 were unknown clones. Among the 42 known
      transcripts, at least 18 are closely involved in the T cell receptor-mediated
      complex signaling cascade, including genes encoding components of the T cell
      receptor and proteins associated with the cytoskeletal scaffold, as well as
      transcription factors. In particular, it was demonstrated that the expression
      levels of Fyb/Slap, L-plastin, and grancalcin were increased during relapse,
      suggesting that the integration of proximal signaling after T cell engagement
      involves the preferential recruitment of these cytoskeleton-associated proteins
      in MCNS. Because very low levels of interleukin-12 receptor beta2 mRNA were
      detected in relapse samples, the interleukin-12 signaling pathway might be
      defective, suggesting that, in MCNS, T cell activation evolves toward a T helper
      2 phenotype. Therefore, the combination of subtractive cloning and differential
      screening constitutes an efficient approach to the identification of genes that
      are likely to be involved in the pathophysiologic processes of MCNS.

PMID- 11961012
TI  - Mutations in theCOL4A4 and COL4A3 genes cause familial benign hematuria.
AB  - Familial benign hematuria (FBH) is a common autosomal dominant disorder
      characterized by the presence of persistent or recurrent hematuria. The clinical
      and pathologic features of this syndrome resemble those of early Alport syndrome
      (AS), and for this reason a common molecular defect has been proposed. The
      COL4A3/4 genes seem to be involved in both autosomal AS and FBH. This study
      involves a linkage analysis for the COL4A3/4 loci and a search for mutations
      within these genes in 11 biopsy-proven FBH families. Haplotype analysis showed
      that linkage to the COL4A3/4 locus could not be excluded in eight of nine
      families. One family was not linked to this locus; however, it included three
      affected women who could be X-linked AS carriers. Two families were too small to
      perform linkage analysis. COL4A3 and COL4A4 mutation screening disclosed six new
      pathogenic mutations, two in the COL4A3 gene (G985V and G1015E) and four in the
      COL4A4 gene (3222insA, IVS23-1G>C, 31del11, and G960R). It is the first time that
      mutations within the COL4A3 gene are described in families with FBH. This study
      clearly demonstrates the main role of the COL4A4 and COL4A3 genes in the
      pathogenesis of FBH.

PMID- 11961013
TI  - Brain uptake of myoinositol after exogenous administration.
AB  - An acute increase in plasma tonicity results in an adaptive increase in brain
      organic osmolyte content, but this process requires several days to occur. Slow
      reaccumulation of brain organic osmolytes may contribute to osmotic
      demyelination. It was investigated whether administration of intravenous
      myoinositol in rats could speed entry of the osmolyte into the brain. Two groups
      of animals were studied: normonatremic animals and animals with hyponatremia (105
      mmol/L) of 3-d duration. Animals were intravenously administered either 1 M NaCl
      to induce a 25 to 28 mM increase in serum sodium concentration over 200 min or an
      infusate that maintained serum sodium concentration. In some animals, myoinositol
      was administered intravenously over the same time period to raise plasma
      myoinositol levels by 5 to 10 mM. Brain myoinositol, electrolyte, and water
      contents were determined at the end of the infusions. In both normonatremic and
      hyponatremic rats, infusion of hypertonic saline without myoinositol or infusion
      of myoinositol without hypertonic saline did not increase brain myoinositol
      levels above control levels. In normonatremic animals, concurrent infusion of
      hypertonic saline and myoinositol increased brain myoinositol levels by about 50%
      above control levels. Brain myoinositol content in animals with uncorrected
      hyponatremia was about 50% of that found in normonatremic controls; concurrent
      infusion of hypertonic saline and myoinositol increased brain myoinositol to
      levels similar to those found in normonatremic controls. Intravenous infusion of
      myoinositol did not alter brain water content compared with animals not infused
      with myoinositol. In conclusion, systemic infusion of myoinositol can rapidly
      increase brain myoinositol content, but only when plasma tonicity is
      concomitantly increased.

PMID- 11961014
TI  - Selective cyclooxygenase-2 inhibition impairs glomerular capillary healing in
      experimental glomerulonephritis.
AB  - Selective cyclooxygenase-2 (COX-2) inhibitors have anti-inflammatory activity and
      reduce proteinuria in experimental membranous glomerulonephritis. Antiangiogenic
      properties of COX-2 inhibitors were recently reported. Whether these properties
      are relevant to the glomerular healing process in inflammatory glomerular
      diseases was investigated. For evaluation of the effects of selective COX-2
      inhibitors on the glomerular healing process in a rat model of
      mesangioproliferative glomerulonephritis (induced by anti-Thy 1.1 antibody), a
      selective COX-2 inhibitor (rofecoxib or celecoxib) or vehicle was administered
      daily from day 1 after disease induction until euthanasia on day 6. Additional
      nephritic rats were treated with rofecoxib or vehicle from day 1 to day 10 and
      were monitored until day 28. Selective COX-2 inhibition led to significant
      increases in mesangiolysis (up to +71%) on days 2 and 6 and in albuminuria (up to
      3.1-fold) on day 6. This augmentation of glomerular capillary damage was
      associated with rarefaction of glomerular endothelial cells, whereas the
      proliferation and activation of mesangial cells were not affected. No significant
      effects on the glomerular influx of polymorphonuclear neutrophils or the
      infiltration and proliferation of monocytes/macrophages at day 2 were noted.
      These effects were independent of systemic hemodynamic features, because
      rofecoxib did not affect systolic BP on day 2 or 5. Nephritic rats treated with
      rofecoxib for 10 d demonstrated persistent glomerular injury at day 28, as
      indicated by increased albuminuria (10-fold) and mesangial type IV collagen
      deposition (+24%). In normal rats, 5-d administration of rofecoxib failed to
      induce albuminuria or morphologic renal damage. In conclusion, selective COX-2
      inhibitors impair glomerular capillary repair after mesangiolysis in rats with
      anti-Thy 1.1 glomerulonephritis. These data suggest that selective COX-2
      inhibitors should be used with caution among patients with inflammatory
      endocapillary glomerular disorders.

PMID- 11961015
TI  - Henoch-Schonlein Purpura in adults: outcome and prognostic factors.
AB  - Henoch-Schonlein Purpura nephritis (HSPN) has been extensively studied in
      children but, its natural history in adults is much less known. A cohort of 250
      adults suffering HSP was retrospectively analyzed for a median follow-up period
      of 14.8 yr. All patients had biopsies consistent with HSP (predominant IgA
      mesangial deposits) associated with purpura, bowel angina, and/or abdominal pain.
      At presentation, palpable purpura was present in 96% of patients, and arthritis
      was reported in 61%, and gastrointestinal involvement in 48%. Thirty-two percent
      of the patients showed renal insufficiency (Creatinine clearance [CrCl] <50
      ml/min), usually associated with proteinuria (99%) and/or hematuria (93%).
      Endocapillary glomerulonephritis was the most frequent lesion on renal biopsy
      (61%). At the end of follow-up, patient survival was only 74%. The first cause of
      death was carcinoma (most of them of respiratory or digestive tract). Regarding
      renal function, 11% of patients reached end-stage renal failure, 13% exhibited
      severe renal failure (CrCl <30 ml/min), and 14% moderate renal insufficiency
      (CrCl <50 ml/min). Clinical remission defined as the absence of proteinuria,
      hematuria, and a normal renal function was achieved in only 20%. This is a
      retrospective study; therefore, it is not possible to demonstrate any steroid
      and/or cyclophosphamide efficacy in diminishing the incidence of renal
      insufficiency. Multivariate analysis demonstrated that renal function impairment
      and proteinuria level at presentation and, on renal biopsy, the degree of
      interstitial fibrosis, percentage of sclerotic glomeruli, and presence of
      glomeruli with fibrinoid necrosis were associated with a poor renal prognosis.
      The data indicate that clinical presentation of HSPN in adults is severe and its
      outcome relatively poor, worse than in children. Identification of clinical and
      histologic prognostic factors may permit the design of appropriate therapeutic
      prospective studies.

PMID- 11961016
TI  - Determinants of modality selection among incident US dialysis patients: results
      from a national study.
AB  - Few studies have comprehensively addressed the association of social factors and
      elements of pre-end-stage renal disease (ESRD) care with the selection of
      dialysis modality. This study examines the relative contribution of demographic,
      medical, social, pre-ESRD, and geographic factors to modality assignment among
      new ESRD patients. Data were collected from the Dialysis Mortality and Morbidity
      Wave 2 Study, a national random sample of 4025 patients in 1996 and 1997. In
      multivariate analyses, the selection of peritoneal dialysis (PD) over
      hemodialysis (HD) was significantly associated with younger age, white race,
      fewer comorbid conditions, and lower serum albumin. Greater use of PD was seen in
      patients who were employed, married, and living with someone before the start of
      ESRD and in those who were more autonomous and more accomplished educationally.
      Patients referred earlier to a nephrologist (> 4 mo versus < or =4 mo) and seen
      more frequently by a nephrologist (> or =2 visits versus < 2 visits) in the pre
      ESRD period had greater PD use. Of the factors listed, 25% of the variability
      (R(2)) in PD use was explained by demographic (4.1%), comorbid (1.2%), social/pre
      ESRD (14.5%), and geographic (5.2%) factors. This study identifies several
      clinical, social, and pre-ESRD factors with the selection of PD, and it
      underscores the importance of patient education, autonomy, and a strong social
      support system in improving rates of PD use in the United States. As pre-ESRD
      patient care is an important contributor to PD use in the United States, greater
      efforts should be expended in improving its delivery earlier in the pre-ESRD
      period.

PMID- 11961017
TI  - Trends in anemia management among US hemodialysis patients.
AB  - This study was undertaken to describe the relationship between hematocrit (Hct)
      and changes in the prescribed dose of erythropoietin (EPO) as well as selected
      patient and process care measures across annual national samples of hemodialysis
      patients from 1994 to 1998. This study uses the cohorts identified in the ESRD
      Core Indicators Project, random samples of 6181, 6241, 6364, 6634, and 7660
      patients, stratified by ESRD Networks drawn for each year from 1994 to 1998.
      Patient demographic and clinical information was collected from October to
      December for each year. Surrogates of iron stores and patterns of iron and EPO
      administration were profiled from 1996 to 1998. Multivariable stepwise linear
      regression analyses were performed to adjust for potential confounding variables
      and to identify independent variables associated with Hct and EPO dose. Mean Hct
      and EPO dose increased each year from 31.1 +/- 5.2% to 34.1 +/- 3.7% and from
      58.2 +/- 41.8 U/kg to 68.2 +/- 55.0 U/kg, respectively (P = 0.0001). Increasing
      Hct was positively associated with male gender, more years on dialysis, older
      age, higher urea reduction ratio and transferrin saturation, prescription of
      intravenous iron, and lower ferritin and EPO dose in multivariable models (all P
      = 0.0001). Male gender, older age, diabetes, higher Hct, and increasing weight,
      urea reduction ration, and transferrin saturation were associated with lower EPO
      doses (all P < 0.01). Conversely, intravenous EPO and iron were associated with
      higher prescribed EPO doses (all P = 0.0001). Although increasing Hct is
      associated with decreasing EPO dose at the patient level, the increase in Hct
      seen across years among the cohorts of hemodialysis patients in the United States
      has been associated with increasing doses of EPO at the population level.

PMID- 11961018
TI  - Receptor for advanced glycation end products on human synovial fibroblasts: role
      in the pathogenesis of dialysis-related amyloidosis.
AB  - An important component of amyloid fibrils in dialysis-related amyloidosis (DRA)
      is beta(2)-microglobulin (beta(2)m) modified with advanced glycation end products
      (AGE). The amyloid deposits are located principally in joint structures, with
      adjacent chronic inflammatory reaction characterized by monocyte infiltration.
      This study examined the interaction of AGE-beta(2)m with human synovial
      fibroblasts and investigated the proinflammatory effects of that interaction. It
      was demonstrated that human synovial fibroblasts constitutively expressed the
      receptor for AGE (RAGE). RAGE expression was detected mainly in synovial intima
      and was upregulated in DRA synovium. (125)I-AGE-beta(2)m bound to immobilized
      human synovial fibroblasts in a specific, dose-dependent manner (K(d) of
      approximately 138.0 nM), and binding was inhibited by anti-RAGE IgG. Incubation
      of human synovial fibroblasts with AGE-beta(2)m induced degradation of this AGE
      modified protein, as well as increased monocyte chemoattractant protein-1 (MCP-1)
      mRNA and protein expression. The amount of MCP-1 produced by AGE-beta(2)m
      stimulated human synovial fibroblasts was sufficient to induce the chemotaxis of
      monocytes. MCP-1 synthesis resulted from engagement of RAGE, because the increase
      in MCP-1 synthesis was attenuated by preincubation of human synovial fibroblasts
      with anti-RAGE IgG. These data provide evidence of RAGE-mediated perturbation of
      human synoviocytes, which may be involved in the pathogenesis of inflammatory
      processes associated with DRA.

PMID- 11961019
TI  - Effects of increased peritoneal clearances on mortality rates in peritoneal
      dialysis: ADEMEX, a prospective, randomized, controlled trial.
AB  - Small-solute clearance targets for peritoneal dialysis (PD) have been based on
      the tacit assumption that peritoneal and renal clearances are equivalent and
      therefore additive. Although several studies have established that patient
      survival is directly correlated with renal clearances, there have been no
      randomized, controlled, interventional trials examining the effects of increases
      in peritoneal small-solute clearances on patient survival. A prospective,
      randomized, controlled, clinical trial was performed to study the effects of
      increased peritoneal small-solute clearances on clinical outcomes among patients
      with end-stage renal disease who were being treated with PD. A total of 965
      subjects were randomly assigned to the intervention or control group (in a 1:1
      ratio). Subjects in the control group continued to receive their preexisting PD
      prescriptions, which consisted of four daily exchanges with 2 L of standard PD
      solution. The subjects in the intervention group were treated with a modified
      prescription, to achieve a peritoneal creatinine clearance (pCrCl) of 60 L/wk per
      1.73 m(2). The primary endpoint was death. The minimal follow-up period was 2 yr.
      The study groups were similar with respect to demographic characteristics, causes
      of renal disease, prevalence of coexisting conditions, residual renal function,
      peritoneal clearances before intervention, hematocrit values, and multiple
      indicators of nutritional status. In the control group, peritoneal creatinine
      clearance (pCrCl) and peritoneal urea clearance (Kt/V) values remained constant
      for the duration of the study. In the intervention group, pCrCl and peritoneal
      Kt/V values predictably increased and remained separated from the values for the
      control group for the entire duration of the study (P < 0.01). Patient survival
      was similar for the control and intervention groups in an intent-to-treat
      analysis, with a relative risk of death (intervention/control) of 1.00 [95%
      confidence interval (CI), 0.80 to 1.24]. Overall, the control group exhibited a 1
      yr survival of 85.5% (CI, 82.2 to 88.7%) and a 2-yr survival of 68.3% (CI, 64.2
      to 72.9%). Similarly, the intervention group exhibited a 1-yr survival of 83.9%
      (CI, 80.6 to 87.2%) and a 2-yr survival of 69.3% (CI, 65.1 to 73.6%). An as
      treated analysis revealed similar results (overall relative risk = 0.93; CI, 0.71
      to 1.22; P = 0.6121). Mortality rates for the two groups remained similar even
      after adjustment for factors known to be associated with survival for patients
      undergoing PD (e.g., age, diabetes mellitus, serum albumin levels, normalized
      protein equivalent of total nitrogen appearance, and anuria). This study provides
      evidence that increases in peritoneal small-solute clearances within the range
      studied have a neutral effect on patient survival, even when the groups are
      stratified according to a variety of factors (age, diabetes mellitus, serum
      albumin levels, normalized protein equivalent of total nitrogen appearance, and
      anuria) known to affect survival. No clear survival advantage was obtained with
      increases in peritoneal small-solute clearances within the range achieved in this
      study.

PMID- 11961020
TI  - Increased oxidative damage to peripheral blood leukocyte DNA in chronic
      peritoneal dialysis patients.
AB  - This study focuses on the extent of oxidative DNA damage in peripheral blood
      leukocytes of chronic peritoneal dialysis (CPD) patients. 8-Hydroxy 2'
      deoxyguanosine (8-OHdG) contents in peripheral leukocyte DNA were measured by an
      HPLC-electrochemical detection method in 24 age- and sex-matched healthy
      subjects, 22 nondialyzed patients with advanced renal failure, and 42 CPD
      patients. Mean 8-OHdG content was the highest in CPD patients, followed by the
      nondialyzed patients, and then by the healthy subjects (19.4 versus 11.9 versus
      8.3/10(6) dG; ANOVA P < 0.001). In nondialyzed subjects, peripheral leukocyte 8
      OHdG contents inversely correlated with renal creatinine clearance (r = -0.772; P
      < 0.001). Deficiency of blood antioxidants in CPD and nondialyzed patients was
      expressed by the lower plasma levels of ascorbate, cholesterol-standardized alpha
      tocopherol and whole-blood reduced glutathione, and the higher levels of whole
      blood oxidized glutathione as compared with healthy subjects (ANOVA P < 0.05).
      Mean serum ferritin and iron levels and transferrin saturation were higher in the
      CPD patients than those in the nondialyzed patients and controls (ANOVA P <
      0.05). Flow cytometric analyses of intracellular reactive oxygen species
      production of peripheral leukocytes showed that spontaneous production by
      granulocytes, as well as phorbol-12-myristate-13-acetate (PMA)-induced production
      by granulocytes, lymphocytes and monocytes, were the highest from CPD patients,
      followed by nondialyzed patients, and then by the healthy subjects (ANOVA P <
      0.05). Forward stepwise multiple regression disclosed that uremia, PD treatment,
      spontaneous and PMA-induced reactive oxygen species production in leukocytes, and
      serum iron were the independent determinants of peripheral leukocyte 8-OHdG
      content (R(2) = 0.769; P < 0.001). In conclusion, profound increased 8-OHdG
      levels in peripheral leukocyte DNA occur in the course of chronic renal failure,
      gradually increase with its progression, and are further exacerbated by PD
      treatment.

PMID- 11961021
TI  - Riboflavin is a determinant of total homocysteine plasma concentrations in end
      stage renal disease patients.
AB  - The effect of thiamine (vitamin B(1)) or riboflavin (vitamin B(2)) availability
      on fasting total homocysteine (tHcy) plasma levels in end-stage renal disease
      patients is unknown. A cross-sectional study was performed in a population of non
      vitamin supplemented patients maintained on continuous ambulatory peritoneal
      dialysis. Red blood cell availability of thiamine (alpha-ETK) and of riboflavin
      (alpha-EGR), along with other predictors of tHcy plasma levels, was considered in
      the analysis. There was a linear association of alpha-EGR with tHcy plasma
      concentrations (P = 0.009), which was not observed for alpha-ETK. Among red blood
      cell vitamins, alpha-EGR was the only predictor of tHcy levels (P = 0.035),
      whereas alpha-ETK, red blood cell pyridoxal-5-phosphate supply (alpha-EGOT) and
      red blood cell folate levels had no effect. The risk for having a high tHcy
      plasma levels within the fourth quartile (plasma tHcy >38.3 micromol/L) was
      increased by an alpha-EGR > median (odds ratio, 4.706; 95% confidence interval,
      1.124 to 19.704; P = 0.026). By way of contrast, alpha-ETK had no effect in these
      analyses. Independent predictors of tHcy plasma levels were serum albumin, alpha
      EGR, red blood cell folate, and certain MTHFR genotypes. A logistic regression
      analysis showed that the MTHFR genotype is a predictor for having a tHcy plasma
      concentration within the fourth quartile. In summary, riboflavin availability, as
      measured by alpha-EGR, is a determinant of fasting tHcy plasma levels in
      peritoneal dialysis patients. This finding may have implications for tHcy
      lowering therapy in individuals with end-stage renal disease.

PMID- 11961022
TI  - Prevalence of low glomerular filtration rate in nondiabetic Americans: Third
      National Health and Nutrition Examination Survey (NHANES III).
AB  - End-stage renal disease is an important and costly health problem. Strategies for
      its prevention are urgently needed. Knowledge of the population-based prevalence
      of renal insufficiency in nondiabetic adults would inform such strategies. Black
      and white nondiabetic adult participants in the Third National Health and
      Nutrition Examination Survey were analyzed. The analysis was stratified by age,
      gender, and race, and four clinically applicable methods were used to assess
      renal function. There were 13,251 complete records for analysis. By the
      Modification of Diet in Renal Diseases (MDRD) GFR (GFR) prediction Equation 7,
      58% (95% confidence interval [CI], 56 to 60%) of the total adult nondiabetic
      black and white US population had MDRD GFR below 80 ml/min per 1.73m(2), 13% (95%
      CI, 11 to 14%) below 60 ml/min per 1.73m(2), and 0.26% (95% CI, 0.19 to 0.33%)
      below 30 ml/min per 1.73m(2). By the Cockcroft-Gault formula, the equivalent
      figures were 39% (95% CI, 37 to 41%), 14% (95% CI, 12% - 16%), and 0.81% (95% CI,
      0.46 to 1.2%), respectively. The findings of an unexpectedly high prevalence of
      low clearance and the increased prevalence of low clearance with age were
      consistent across the four clearance estimation methods used and for each race
      sex stratum. The absolute magnitude of the prevalence of low clearance was,
      however, dependent on the clearance method used. Assessed by estimation from
      serum creatinine, low clearance may be very common, particularly with advancing
      age. The prognosis (in terms of risk for progression and end-stage renal disease)
      of low clearance in unreferred populations may differ from that in referred
      populations and requires further study.

PMID- 11961023
TI  - Refining predictive models in critically ill patients with acute renal failure.
AB  - Mortality rates in acute renal failure remain extremely high, and risk-adjustment
      tools are needed for quality improvement initiatives and design (stratification)
      and analysis of clinical trials. A total of 605 patients with acute renal failure
      in the intensive care unit during 1989-1995 were evaluated, and demographic,
      historical, laboratory, and physiologic variables were linked with in-hospital
      death rates using multivariable logistic regression. Three hundred and fourteen
      (51.9%) patients died in-hospital. The following variables were significantly
      associated with in-hospital death: age (odds ratio [OR], 1.02 per yr), male
      gender (OR, 2.36), respiratory (OR, 2.62), liver (OR, 3.06), and hematologic
      failure (OR, 3.40), creatinine (OR, 0.71 per mg/dl), blood urea nitrogen (OR,
      1.02 per mg/dl), log urine output (OR, 0.64 per log ml/d), and heart rate (OR,
      1.01 per beat/min). The area under the receiver operating characteristic curve
      was 0.83, indicating good model discrimination. The model was superior in all
      performance metrics to six generic and four acute renal failure-specific
      predictive models. A disease-specific severity of illness equation was developed
      using routinely available and specific clinical variables. Cross-validation of
      the model and additional bedside experience will be needed before it can be
      effectively applied across centers, particularly in the context of clinical
      trials.

PMID- 11961024
TI  - Preemptive kidney transplantation: the advantage and the advantaged.
AB  - It remains unclear whether preemptive transplantation is beneficial, and if so,
      who benefits. A total of 38,836 first, kidney-only transplants between 1995 and
      1998 were retrospectively studied. A surprising 39% of preemptive transplants
      were from cadaver donors, and the proportions of cadaver donor transplants that
      were preemptive changed little, from 7.3% in 1995 to 7.7% in 1998. Preemptive
      transplants using cadaver donors were more likely among recipients aged 0 to 17
      yr versus 18 to 29 yr (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.94
      to 3.17), white versus black (OR, 2.33; 95% CI, 2.03 to 2.68), able to work
      versus unable to work (OR, 1.42; 95% CI, 1.26 to 1.61), covered by private
      insurance versus Medicare (OR, 4.77; 95% CI, 4.26 to 5.32), or recipients with a
      college degree versus no college degree (OR, 1.34; 95% CI, 1.17 to 1.54).
      Preemptive transplants were less likely for Hispanics versus non-Hispanics (OR,
      0.57; 95% CI, 0.50 to 0.67), patients with type 2 versus type 1 diabetes (OR,
      0.76; 95% CI, 0.61 to 0.96), and for 2 to 5 HLA mismatches compared with 0 HLA
      mismatches (OR range, 0.77 to 0.82). In adjusted Cox proportional hazards
      analysis, the relative risk of graft failure for preemptive transplantation was
      0.75 (0.67 to 0.84) among 25,758 cadaver donor transplants and 0.73 (0.64 to
      0.83) among 13,078 living donor transplants, compared with patients who received
      a transplant after already being on dialysis. Preemptive transplantation was
      associated with a reduced risk of death: 0.84 (0.72 to 0.99) for cadaver donor
      transplants and 0.69 (0.56 to 0.85) for living donor transplants. Thus,
      preemptive transplantation, which is associated with improved patient and graft
      survival, is less common among racial minorities, those who have less education,
      and those who must rely on Medicare for primary payment. Alterations in the
      payment system, emphasis on early referral, and changes in cadaver kidney
      allocation could increase the number of patients who benefit from preemptive
      transplantation.

PMID- 11961025
TI  - Withdrawal of cyclosporine or prednisone six months after kidney transplantation
      in patients on triple drug therapy: a randomized, prospective, multicenter study.
AB  - Uncertainty exists regarding the necessity of continuing triple therapy
      consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone
      (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were
      randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug
      therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels
      were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo
      after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients
      after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P =
      0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven
      chronic rejection was present in one patient in the control group, in nine
      patients after CsA withdrawal (P = 0.006 versus control group); and in four
      patients after discontinuation of Pred (NS). Graft loss occurred in two versus
      one patient after CsA or Pred withdrawal, respectively, and in two patients in
      the control group (NS). Patients who successfully withdrew CsA had a
      significantly lower serum creatinine during follow-up. Pred withdrawal resulted
      in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio
      increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a
      significantly increased incidence of biopsy-proven acute and chronic rejection.
      Pred withdrawal was safe and resulted in a reduction in mean arterial pressure.
      However, patient and graft survival and renal function 2 yr after RTx were not
      different among groups.

PMID- 11961026
TI  - Association of hepatitis C with posttransplant diabetes in renal transplant
      patients on tacrolimus.
AB  - Posttransplant diabetes mellitus (PTDM) remains a common complication of
      immunosuppression. Although multiple risk factors have been implicated, none have
      been clearly identified as predisposing to the increased PTDM frequency observed
      in patients on tacrolimus. Hepatitis C virus (HCV) has been associated with
      diabetes and is a significant renal transplant comorbidity. In this study,
      records of 427 kidney recipients who had no known diabetes before transplantation
      were retrospectively examined. A multivariate logistic regression model was fit
      with covariates that had unadjusted relationships with PTDM to examine the
      independent relationship of HCV and the odds of development of PTDM by 12 mo
      posttransplant. A potential interaction between HCV and the use of tacrolimus as
      maintenance therapy on the odds of the development of PTDM was examined. Overall,
      PTDM occurred more frequently in HCV(+) than HCV(-) patients (39.4% versus 9.8%;
      P = 0.0005). By multivariate logistic regression, HCV (adjusted odds ratio [OR],
      5.58; 95% confidence interval [CI], 2.63 to 11.83; P = 0.0001), weight at
      transplantation (adjusted OR 1.028; 95% CI, 1.00 to 1.05; P = 0.001), and
      tacrolimus (adjusted OR, 2.85; 95% CI, 1.01 to 5.28; P = 0.047) were associated
      with PTDM. A significant interaction (P = 0.0001) was detected between HCV status
      and tacrolimus use for the odds of PTDM. Among the HCV(+) cohort, PTDM occurred
      more often in tacrolimus-treated than cyclosporine A-treated patients (57.8%
      versus 7.7%; P < 0.0001). PTDM rates in HCV(-) patients were similar between the
      two calcineurin inhibitors (10.0% versus 9.4%; P = 0.521, tacrolimus versus
      cyclosporine A). In conclusion, HCV is strongly associated with PTDM in renal
      transplant recipients and appears to account for the increased diabetogenicity
      observed with tacrolimus.

PMID- 11961027
TI  - Vasodilatory N-methyl-D-aspartate receptors are constitutively expressed in rat
      kidney.
AB  - N-methyl-D-aspartate receptor (NMDA-R) is an amino acid receptor and membrane
      calcium channel. NMDA-R is activated by binding of coagonists, L-glutamine and L
      glycine. In the brain, calcium entry via NMDA-R activates type I nitric oxide
      synthase (NOS I). The kidney also contains NOS I and vasodilates in response to L
      glycine. In this study, NMDA-R mRNA was demonstrated in rat kidney cortex by
      reverse transcriptase-PCR and cDNA sequencing. NMDA-R protein was demonstrated in
      kidney cortex by immunoblotting. To study the functional role of renal NMDA-R,
      renal hemodynamic effects of NMDA-R inhibition were assessed in rats using a
      blocker of the NMDA calcium channel (75 mg/kg MK-801 intraperitoneally) or an
      inhibitor of glycine binding to NMDA-R (30 mg/kg 5,7-dichlorokynurenic acid
      intraperitoneally). Renal blood flow was measured by perivascular pulse Doppler.
      GFR was measured by 3H-inulin clearance. Measurements were made before and during
      glycine infusion. Both NMDA-R antagonists caused renal vasoconstriction and
      attenuated the renal vasodilatory response to glycine infusion. These effects
      were not mediated by the renal nerves. The glycine response was not inhibited by
      aortic snare used to mimic the effects of NMDA-R inhibitors on basal renal blood
      flow. NMDA-R are expressed in kidney cortex, where they exert a tonic
      vasodilatory influence and may account for the vasodilatory response to glycine
      infusion.

PMID- 11961028
TI  - N-linked glycosylation is critical for the plasma membrane localization of
      nephrin.
AB  - The expression pattern, subcellular localization, and the role of glycosylation
      of the human nephrin was examined in transfected cells. Stable cell lines,
      constitutively expressing a full-length human nephrin cDNA construct, were
      generated from transfected immortalized mouse podocytes (IMP) and a human
      embryonic kidney cell line (HEK-293). Immunofluorescence confocal microscopy of
      transfected cells showed plasma membrane localization of the recombinant nephrin.
      Immunoblotting showed that the recombinant nephrin expressed in transfected cell
      lines migrated as a double band with a molecular weight of 185 kD. When cells
      were treated with the N-glycosylation inhibitor, tunicamycin, the molecular
      weight of nephrin was decreased to a single immunoband of 150 kD, indicating that
      the shift in the electrophoretic migration of nephrin is due to N-linked
      carbohydrate moieties. It was further shown that this glycosylation process is
      highly sensitive to inhibition by tunicamycin, which is a naturally occurring
      antibiotic, leading to retention of nonglycosylated nephrin molecules in the
      endoplasmic reticulum. It was concluded that N-glycosylation of nephrin is
      crucial for its proper folding and thereby plasma membrane localization;
      therefore, inhibition of this process might be an important factor in the onset
      of pathogenesis of some acquired glomerular diseases.

PMID- 11961029
TI  - Immunotactoid glomerulopathy.

PMID- 11961030
TI  - Proteomics and the kidney.
AB  - Proteomics can be defined as "the systematic analysis of proteins for their
      identity, quantity, and function." The central concept is "multiplexing," i.e.,
      simultaneous analysis of all proteins in a defined protein population, rather
      than investigation of one protein at a time, as in traditional biochemistry. Two
      major approaches have been described: (1) mass spectrometry-based approaches and
      (2) protein micro-array approaches. The purpose of this Science Watch article is
      to describe the fundamental features of these two approaches and to speculate on
      how proteomics will be useful in nephrology and nephrology research in the coming
      years.

PMID- 11961031
TI  - T cells and minimal change disease.

PMID- 11961032
TI  - Anemia management in chronic kidney disease: role of factors affecting epoetin
      responsiveness.

PMID- 11961033
TI  - The ADEMEX Study: make haste slowly.

PMID- 11961034
TI  - Letter from the authors of "Improved Growth in Young Children with Severe Chronic
      Renal Insufficiency Who Use Specified Nutritional Therapy," which appeared on
      pages 2418-2426 of the November 2001 issue of JASN.

PMID- 11961037
TI  - Characteristics of the fetal/maternal interface with potential usefulness in the
      development of future immunological and pharmacological strategies.
AB  - A study of the fundamental biology of the maternal-fetal interface reveals the
      complex interactions among multiple cell types and regulatory factors necessary
      to support a successful pregnancy. Cells of decidua and trophoblast lineages play
      central roles in creating the maternal-fetal interface and are sources of
      regulatory factors that can determine the quality and success of pregnancy. The
      regulatory factors considered here are major placental histocompatibility complex
      proteins, pregnancy-specific regulatory factors for uterine inflammatory cells,
      and hormone-controlled placental multidrug-resistant transport systems. Potential
      targets are discussed and presented as areas where researchers may identify novel
      pharmacological and immunological strategies that eventually will extend to the
      clinic to improve the quality and success of pregnancy.

PMID- 11961038
TI  - Genetic manipulation of noradrenergic neurons.
AB  - The neurotransmitter norepinephrine has been the focus of intense investigation
      for nearly a century. With advances in technology come novel approaches for
      testing hypotheses about the physiological roles of norepinephrine and the genes
      involved in norepinephrine (NE) biosynthesis, metabolism, and noradrenergic
      signaling. Homologous recombination techniques, which generate mice deficient in
      specific gene products, aid the integrated physiologist and pharmacologist in the
      evaluation of protein function. Mouse models lacking proteins involved in NE
      biosynthesis or metabolism provide tools to expand the knowledge previously
      gleaned from pharmacologic studies. Removal of the biosynthetic enzymes tyrosine
      hydroxylase and dopamine-beta-hydroxylase yield animals deficient in
      norepinephrine and have been used to further examine the role of NE in diverse
      physiologic roles. Complete removal of the vesicular monoamine transporter has
      demonstrated that mobilizing neurotransmitters to vesicles is required for animal
      survival. Lastly, the generation of animals in which the ability to remove NE
      from the synapse is impaired (norepinephrine transporter deficiency and
      extraneuronal monoamine transporter deficiency) and in which the enzymes
      responsible for the metabolism of NE have been removed (catechol-O
      methyltransferase and monoamine oxidase) has facilitated the study of the long
      term physiological consequences of altered NE homeostasis.

PMID- 11961039
TI  - Binding and functional comparisons of two types of tumor necrosis factor
      antagonists.
AB  - Two tumor necrosis factor (TNF) antagonists infliximab (a chimeric monoclonal
      antibody) and etanercept (a p75 TNF receptor/Fc fusion protein) have been
      approved for treatment of rheumatoid arthritis. However, these agents have shown
      different degrees of clinical benefit in controlled clinical trials in other TNF
      mediated diseases such as Crohn's disease (CD) and psoriasis. We investigated
      whether structural differences between these two antagonists translate into
      different binding and functional characteristics. To study the binding of
      infliximab and etanercept to both the soluble and cell-surface transmembrane
      forms of TNF, a variety of in vitro binding and cell-based assays were performed.
      Binding assays using (125)I-labeled TNF showed that infliximab binds to both
      monomer and trimer forms of soluble TNF (sTNF), whereas etanercept binding is
      restricted to the trimer form. Infliximab formed stable complexes with sTNF,
      whereas etanercept formed relatively unstable complexes, resulting in release of
      dissociated TNF. KYM-1D4 cell killing assays and human umbilical vein endothelial
      cell activation assays demonstrated that TNF that had dissociated from etanercept
      was bioactive. Infliximab also formed more stable complexes with the
      transmembrane form of TNF expressed on transfected cells relative to analogous
      complexes formed with etanercept. Additionally, more infliximab molecules bound
      to the transmembrane TNF with higher avidity than etanercept. Although both
      infliximab and etanercept inhibited transmembrane TNF-mediated activation of
      human endothelial cells, infliximab was significantly more effective. The
      differences between infliximab and etanercept in their TNF binding
      characteristics may help explain their differential efficacy in CD and psoriasis
      clinical trials.

PMID- 11961040
TI  - Three-dimensional quantitative structure-activity relationship for inhibition of
      human ether-a-go-go-related gene potassium channel.
AB  - The protein product of the human ether-a-go-go gene (hERG) is a potassium channel
      that when inhibited by some drugs may lead to cardiac arrhythmia. Previously, a
      three-dimensional quantitative structure-activity relationship (3D-QSAR)
      pharmacophore model was constructed using Catalyst with in vitro inhibition data
      for antipsychotic agents. The rationale of the current study was to use a
      combination of in vitro and in silico technologies to further test the
      pharmacophore model and qualitatively predict whether molecules are likely to
      inhibit this potassium channel. These predictions were assessed with the
      experimental data using the Spearman's rho rank correlation. The antipsychotic
      based hERG inhibitor model produced a statistically significant Spearman's rho of
      0.71 for 11 molecules. In addition, 15 molecules from the literature were used as
      a further test set and were also well ranked by the same model with a
      statistically significant Spearman's rho value of 0.76. A Catalyst General hERG
      pharmacophore model was generated with these literature molecules, which
      contained four hydrophobic features and one positive ionizable feature. Linear
      regression of log-transformed observed versus predicted IC(50) values for this
      training set resulted in an r(2) value of 0.90. The model based on literature
      data was evaluated with the in vitro data generated for the original 22 molecules
      (including the antipsychotics) and illustrated a significant Spearman's rho of
      0.77. Thus, the Catalyst 3D-QSAR approach provides useful qualitative predictions
      for test set molecules. The model based on literature data therefore provides a
      potentially valuable tool for discovery chemistry as future molecules may be
      synthesized that are less likely to inhibit hERG based on information provided by
      a pharmacophore for the inhibition of this potassium channel.

PMID- 11961042
TI  - Modulation of the rat hippocampal dinucleotide receptor by adenosine receptor
      activation.
AB  - Diadenosine pentaphosphate (Ap(5)A) and ATP stimulate an intracellular free
      calcium concentration ([Ca(2+)](I)) increase in rat hippocampal synaptosomes via
      different receptors as demonstrated by the lack of cross-desensitization between
      Ap(5)A and ATP responses. The ATP response was inhibited by P2 receptor
      antagonists and not by the dinucleotide receptor antagonist, diinosine
      pentaphosphate (Ip(5)I). In contrast, the Ap(5)A response was inhibited by Ip(5)I
      but not by P2 receptor antagonists. Studies in single hippocampal synaptic
      terminals showed that 31% of them responded to Ap(5)A by a [Ca(2+)](i) increase.
      Adenosine receptors (A(1), A(2A), and A(3)) were also present in isolated
      terminals as demonstrated by immunohistochemistry. The activation of A(1) or
      A(2A) receptors by specific agonists changed the sigmoid concentration-response
      curve for Ap(5)A (EC(50) = 33.5 +/- 4.5 microM) into biphasic curves. When the
      high-affinity adenosine receptors A(1) or A(2A) were activated, the Ap(5)A dose
      response curves showed a high-affinity component with EC(50) values of 41.1 +/-
      1.9 pM and 99.9 +/- 10.2 nM, respectively. The low-affinity component showed
      EC(50) values of 17.1 +/- 0.8 and 21.6 +/- 1.4 microM for A(1) and A(2A) receptor
      activation, respectively. However, the adenosine A(3) receptor activation induced
      a right shift of the dinucleotide concentration-response curve, showing an EC(50)
      value of 331.4 +/- 54.6 microM. In addition, in the presence of the A(2A)
      agonist, the Ap(5)A calcium influx responses were increased up to 300% of the
      control values. These results clearly demonstrate that the activation of
      presynaptic adenosine receptors is able to modulate the dinucleotide response in
      hippocampal nerve terminals.

PMID- 11961041
TI  - Hepoxilin analogs inhibit bleomycin-induced pulmonary fibrosis in the mouse.
AB  - Bleomycin has been suggested to incite plasma extravasation and influx of
      inflammatory cells leading to pulmonary fibrosis. We hypothesized that stable
      analogs of the 12-lipoxygenase product, hepoxilin, may attenuate these effects.
      We initially investigated the effects of the four hepoxilin analogs (PBT-1 to -4)
      coadministered intradermally with bleomycin and found that PBT-1 and -2
      significantly opposed the vascular permeability effects of bleomycin in rat skin.
      We subsequently tested the hepoxilin analogs for their actions in opposing the
      intratracheal bleomycin-evoked acute inflammatory phase of lung fibrosis in the
      mouse, characterized by a marked accumulation of macrophages and an increase in
      the rate of collagen synthesis and deposition. We found that the bleomycin-evoked
      effects on macrophage influx were inhibited by all the hepoxilin analogs (PBT-1, 
      3, and -4 > PBT-2) administered i.p. for 8 days. Increased total lung collagen
      was completely abrogated by PBT-1 and -2, whereas PBT-3 and -4 had little effect.
      A dose-response study with PBT-1 indicated that the effective dose for inhibition
      of bleomycin-induced inflammatory and histological changes was below 10
      microg/day. These studies demonstrate an in vivo action of stable analogs of
      hepoxilin and support an effect on inflammation and vascular permeability from
      these novel compounds, especially for PBT-1.

PMID- 11961043
TI  - The role of transmembrane helix 5 in agonist binding to the human H3 receptor.
AB  - We have used alanine scanning mutagenesis to identify residues in transmembrane
      domain 5 of the histamine H3 receptor that are important for agonist binding. All
      of the mutants generated were functionally expressed as demonstrated by their
      ability to bind [(125)I]iodoproxyfan with comparable affinity to the wild-type
      receptor and their ability to inhibit forskolin-stimulated cAMP formation when
      activated by histamine. Many mutations produced small changes in the potency of
      histamine, but the most pronounced reduction in potency and affinity of the
      agonists, histamine, R-alpha-methylhistamine, imetit, and impentamine, was seen
      with mutation of glutamate 206. Our modeling suggests that this residue plays a
      key role in ligand binding by interacting with the imidazole ring of histamine.
      Interestingly, L199A greatly reduced agonist potency in functional assays but had
      only minor effects on agonist affinity, implicating a role for this residue in
      the mechanism of receptor activation. We also studied the functional effects of
      the mutations by linking the receptor to calcium signaling using a chimeric G
      protein. A comparison of the two functional assays demonstrated contrasting
      effects on agonist activity. Histamine, imetit, and impentamine were full
      agonists in the cAMP assay, but imetit exhibited only partial agonist activity
      through the chimeric G protein. Furthermore, impentamine, another potent agonist
      in the cAMP assay, was only able to activate the E206A mutant in the calcium
      assay despite being inactive at the wild-type receptor. These observations
      suggest that the agonist receptor complexes formed by these three different H3
      agonists are not conformationally equivalent.

PMID- 11961044
TI  - Involvement of Rho-kinase pathway for angiotensin II-induced plasminogen
      activator inhibitor-1 gene expression and cardiovascular remodeling in
      hypertensive rats.
AB  - Angiotensin II (Ang II) is a potent stimulator of plasminogen activator inhibitor
      1 (PAI-1) expression, which is an important regulator of pathogenesis of
      atherosclerosis. Rho-kinase, a downstream target protein of small GTP-binding
      protein Rho, plays a key role for various cellular functions. We evaluated the
      cardioprotective effects of a specific Rho-kinase inhibitor, (R)-(+)-trans-N-(4
      pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632), and an Ang II type 1
      receptor antagonist, candesartan, on PAI-1 gene expression and cardiovascular
      remodeling in Ang II-induced hypertensive rats. Rats given Ang II alone (200
      ng.kg(-1).min(-1)) were compared with rats also receiving Ang II plus Y-27632 or
      Ang II plus candesartan. Ang II-induced PAI-1 mRNA up-regulation in the left
      ventricle was inhibited by Y-27632 and candesartan. In addition, increased RhoA
      protein, Rho-kinase, and c-fos gene expression, and myosin light chain
      phosphorylation were suppressed by Y-27632 and candesartan. In contrast, Y-27632
      had no effect on Ang II-stimulated phospho-p42/p44 extracellular signal-regulated
      kinases (ERK) and phospho-p70S6 kinase activities, which are reported to be
      involved in Ang II-induced protein synthesis. Moreover, activated Ang II-induced
      phosphorylation of ERK and p70S6 kinase were blocked by candesartan. Y-27632 or
      candesartan administration resulted in significant improvements in the wall-to
      lumen ratio, perivascular fibrosis, and myocardial fibrosis. These results
      suggested that differential activation of Rho-kinase and ERK pathways may play a
      critical role in Ang II-induce PAI-1 gene expression, and up-regulation of Rho
      kinase plays a key role in the pathogenesis of Ang II-induced hypertensive rats.
      Thus, inhibition of the Rho-kinase pathway may be at least a useful therapeutic
      strategy for treating cardiovascular remodeling.

PMID- 11961045
TI  - Pharmacokinetic analysis of in vivo disposition of succinylated proteins targeted
      to liver nonparenchymal cells via scavenger receptors: importance of molecular
      size and negative charge density for in vivo recognition by receptors.
AB  - In vivo disposition characteristics of succinylated (Suc-) proteins were studied
      after intravenous injection in mice in relation to their molecular
      characteristics as negatively charged macromolecules. Recombinant superoxide
      dismutase (SOD; molecular mass, 32 kDa), bovine serum albumin (BSA; molecular
      mass, 67 kDa), and bovine IgG (molecular mass, 150 kDa) were used to produce
      succinylated derivatives with different degrees of modification. (111)In-labeled
      Suc-SODs were rapidly excreted into the urine with no significant hepatic uptake.
      In contrast, (111)In-Suc-BSA and Suc-IgG were significantly taken up by liver
      nonparenchymal cells via scavenger receptors (SRs) according to the degree of
      succinylation and the dose injected. Interestingly, highly succinylated BSAs
      exhibited significant accumulation in the kidney at higher doses when the hepatic
      uptake was saturated. Pharmacokinetic analysis demonstrated that the hepatic
      uptake of succinylated proteins depended on the molecular size and the estimated
      surface density of succinylated amino residues. Further analysis based on a
      physiological pharmacokinetic model, involving a saturable process with Michaelis
      Menten kinetics, revealed that the surface density of negative charges was
      correlated with the affinity of larger succinylated proteins for the hepatic SRs.
      Thus, the present study has provided useful basic information for a therapeutic
      strategy and the molecular design of succinylated proteins for use as drug
      carriers and therapeutic agents per se for SR-mediated targeting in vivo.

PMID- 11961046
TI  - The role of superoxide and nuclear factor-kappaB signaling in N-methyl-D
      aspartate-induced necrosis and apoptosis.
AB  - N-Methyl-D-aspartate (NMDA) receptor-mediated cell death is complex, probably
      involving elements of necrosis and apoptosis. The mechanisms underlying this
      phenomenon are incompletely understood but have been suggested to involve
      reactive oxygen species such as nitric oxide and superoxide anion (O(2)) and
      nuclear factor-kappaB (NF-kappaB) signaling. In this study, we used a selective
      nonpeptidyl superoxide dismutase mimetic (M40403) and SN50, a peptide inhibitor
      of NF-kappaB translocation, to investigate the role of O(2) and the potential
      downstream signaling molecules in cell death induced by activation of the NMDA
      receptor. Application of NMDA to a mixed neuronal/glial forebrain culture
      resulted in an early increase in the release of cytoplasmic lactate dehydrogenase
      (LDH), which peaked at 4 h. This was followed by a reduction in mitochondrial
      metabolism of the dye MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium
      bromide] that continued to decrease throughout the 20-h exposure. A substantial
      increase in DNA fragmentation as measured by an enzyme-linked immunosorbent assay
      (ELISA) specific for DNA-associated histone proteins (nucleosomes) was observed
      at 7 and 20 h. M40403 and SN50 blocked NMDA-induced changes in LDH release at 2,
      4, and 20 h, MTT metabolism at 4 and 20 h, and DNA fragmentation at 20 h as
      measured by the ELISA and by an increase in terminal dUTP-nick end labeling.
      M40403 also prevented NMDA-induced nuclear transport of NF-kappaB and increased
      expression of Bax relative to Bcl-X(L). SN50 was also able to block NMDA-induced
      cell death as well as the increased Bax/Bcl-X(L) ratio. Time course studies and
      experiments with SN50 and M40403 suggest that O(2) production and NF-kappaB
      translocation may be involved in necrosis and apoptosis, but the latter also
      requires an increased expression of Bax. The ability of M40403 to prevent NMDA
      induced cell death relatively early in this cascade suggests its potential
      therapeutic utility in central nervous systems diseases such as stroke that are
      associated with increased NMDA receptor-mediated production of O(2).

PMID- 11961047
TI  - Gastric effects of galanin and its interaction with leptin on brainstem neuronal
      activity.
AB  - Galanin is a 29-amino acid peptide that is widely distributed throughout the
      central nervous system, peripheral nervous system, and gastrointestinal and
      genitourinary tracts. Leptin is a hormone secreted from adipose tissue and the
      gut and other tissues. In this study, using an in vitro neonatal rat preparation,
      we investigated the gastric effects of galanin and its interaction with leptin on
      nucleus tractus solitarius (NTS) neurons receiving gastric vagal inputs. We
      showed that peripheral gastric galanin (300 nM) produced a mean inhibition
      response of 53.2 +/- 2.1% compared with the control level of 100% (P < 0.01) in
      27 of 58 neurons tested. A concentration-dependent effect of galanin on NTS
      neuronal activity was observed. The galanin receptor antagonist [galanin-(1-12)
      Pro3-(Ala-Leu)2-Ala amide], or M40, significantly reversed the galanin-induced
      inhibition effect (P < 0.01). In contrast, we showed that the peripheral gastric
      effect of leptin (10 nM) produced a mean activation response of 167.4 +/- 8.2%
      compared with the control level. The NTS neurons that we recorded could respond
      to both galanin and leptin or respond to only one of them. Subsequently, we
      evaluated gastric interactions between galanin and leptin on NTS unitary activity
      when galanin (100 nM) and leptin (10 nM) were applied together in the gastric
      compartment. We observed that the effect of leptin when applied alone (168.8 +/-
      7.7%) was reduced to 146.2 +/- 4.7% after coapplication of both compounds (P <
      0.05 compared with leptin alone; P < 0.01 compared with galanin alone, 55.1 +/-
      3.2%). Our data suggest that galanin modulates the leptin signals, which regulate
      the ingestive process in neonates.

PMID- 11961049
TI  - On the role of phosphatase in regulation of cardiac L-type calcium current by
      cyclic GMP.
AB  - Does cGMP, via protein kinase G, inhibit cAMP-stimulated Ca(2+) current
      (I(Ca(L))) in mammalian ventricular myocytes by phosphorylating the calcium
      channel at a site different from that acted on by cAMP or by dephosphorylating
      the calcium channel through phosphatase(s)? We tested these possibilities in
      guinea pig ventricular myocytes superfused with Tyrode's solution (35 degrees C)
      and dialyzed with adenosine 5'-O-(3-thiotriphosphate) ([ATPgammaS](pip)).
      ATPgammaS is a kinase substrate but thiophosphorylated proteins are not
      phosphatase substrates. With 5 mM [ATPgammaS](pip), I(Ca(L)) increased gradually
      over 20 to 25 min and then rapidly in the presence of 3-isobutyl-1
      methylxanthine. 8-Bromo-cGMP (8-Br-cGMP; 1 mM) did not inhibit I(Ca(L))
      significantly (-3 +/- 11.8%, n = 21) in contrast to results with ATP dialysis ().
      Similar results were obtained with 0.1 mM carbachol (CCh). I(Ca(L)) increased
      after longer dialysis (>/=40 min) with ATPgammaS; again, 8-Br-cGMP had no effect.
      Also, isoproterenol (ISO) did not stimulate and CCh, alone or in the presence of
      ISO, did not inhibit I(Ca(L)). Block of CCh effect by ATPgammaS, although
      consistent with cGMP action in muscarinic inhibition, could be explained by
      guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) formation from ATPgammaS via
      nucleoside diphosphate kinase. GTPgammaS uncouples muscarinic and beta
      adrenoceptors from intracellular effectors. Failure of 8-Br-cGMP to reduce
      I(Ca(L)) irreversibly excludes calcium channel phosphorylation as an inhibitory
      mechanism. We propose that cGMP inhibits I(Ca(L)) by activating phosphatase(s) in
      guinea pig ventricular myocytes.

PMID- 11961048
TI  - Role of cyclooxygenase-2 in neuronal cell cycle activity and glutamate-mediated
      excitotoxicity.
AB  - In previous studies we found that neuronal overexpression of human cyclooxygenase
      (COX)-2 in transgenic mice potentiated excitotoxicity in vivo and in vitro. To
      clarify the molecular mechanisms involved in COX-2-mediated potentiation of
      excitotoxicity, we used cDNA microarray to identify candidate genes the
      expression of which is altered in the cerebral cortex of homozygous human hCOX-2
      transgenic mice. We found that the mRNA expression of the cell cycle kinase (CDK)
      inhibitor-inhibitor kinase (INK) p18(INK4), a specific inhibitor of CDK 4,6,
      which controls the activation of the retinoblastoma (Rb) tumor suppressor protein
      phosphorylation, was decreased in the brain of adult hCOX-2 homozygous
      transgenics. Conversely, chronic treatment of the hCOX-2 transgenics with the
      preferential COX-2 inhibitor nimesulide reversed the hCOX-2-mediated decrease of
      cortical p18(INK4) mRNA expression in the brain. Further in vitro studies
      revealed that in primary cortico-hippocampal neurons derived from homozygous hCOX
      2 transgenic mice, COX-2 overexpression accelerates glutamate-mediated apoptotic
      damage that is prevented by the CDK inhibitor flavoperidol. Moreover, treatment
      of wild-type primary cortico-hippocampal neuron cultures with the COX-2
      preferential inhibitor nimesulide significantly attenuated glutamate-mediated
      apoptotic damage, which coincided with inhibition of glutamate-mediated pRb
      phosphorylation. These data indicate that hCOX-2 overexpression causes neuronal
      cell cycle deregulation in the brain and provides further rationale for targeting
      neuronal COX-2 in neuroprotective therapeutic research.

PMID- 11961050
TI  - Clinical pharmacokinetics of 5-aminolevulinic acid in healthy volunteers and
      patients at high risk for recurrent bladder cancer.
AB  - 5-Aminolevulinic acid (ALA) is a precursor of protoporphyrin IX (PpIX) that is
      being evaluated for use in photodiagnosis and phototherapy of malignant and
      nonmalignant disorders. Previous clinical studies using topical, oral, and
      intravesical administration have been conducted in attempts to determine the
      optimal route of administration for ALA. The purpose of these studies was to
      examine the systemic pharmacokinetics and elimination of ALA, the bioavailability
      of ALA after oral and intravesical doses, and the factors that affect ALA
      concentrations in the bladder during intravesical treatment. The disposition of
      ALA was evaluated in six healthy volunteers receiving single intravenous and oral
      doses (100 mg) and eight patients at high risk for recurrent bladder cancer
      receiving an intravesical dose (1.328 g) of ALA. The mean (+/-S.D.) plasma area
      under the plasma concentration-time curve from time 0 to infinity of PpIX (0.20
      +/- 0.11 microg small middle dot h/ml) after intravenous administration of ALA
      was not significantly different from that observed after oral administration of
      ALA (0.15 +/- 0.11 microg*h/ml; P = 0.49). ALA terminal half-life was
      approximately 45 min after intravenous or oral administration. The oral
      bioavailability of ALA was approximately 60%. After intravesical administration,
      urine production was largely responsible for decreases in ALA concentration in
      the bladder, with less than 1% being absorbed into the systemic circulation. In
      summary, oral and intravenous administration of ALA at these doses results in
      modest plasma levels of PpIX. Regional administration (i.e., intravesical) of ALA
      resulted in a significant pharmacokinetic advantage, with urinary bladder being
      exposed to concentrations approximately 20,000-fold higher than systemic
      circulation.

PMID- 11961052
TI  - Pharmacokinetics and cell trafficking dynamics of 2-amino-2-[2-(4
      octylphenyl)ethyl]propane-1,3-diol hydrochloride (FTY720) in cynomolgus monkeys
      after single oral and intravenous doses.
AB  - The pharmacokinetics and cell trafficking dynamics of 2-amino-2-[2-(4
      octylphenyl)ethyl]propane-1,3-diol hydrochloride (FTY720), a novel
      immunosuppressive agent, were examined in cynomolgus monkeys (three males and
      three females). After single doses of 0.1 mg/kg p.o. or i.v. bolus and 1 mg/kg
      p.o. were administered to the animals, the concentrations of FTY720, and the
      numbers of lymphocytes, CD20+CD2-B cells, and CD2+CD20-T cells in blood were
      measured over 23 days. A linear three-compartment model characterized the time
      course of FTY720 concentrations with a terminal half-life of about 31 h,
      clearance of about 0.53 l/h/kg, and bioavailability of about 38%. The dynamic
      responses were not area under the curve (or dose) proportional for either males
      or females. An indirect response model with a distribution pool captured the cell
      trafficking data for all doses for each cell type, where initial blood counts
      (R(0)) were about 7650, 2100, and 5250 cells/microl; maximum fractional
      inhibition (I(max)) about 0.88, 0.85, and 0.91; influx (k(in)) about 6014, 1312,
      and 5662 cells/microl/h; efflux (k(out)) about 0.798, 0.555, and 1.08 h(-1);
      intercompartmental k(cp) about 0.134, 0.192, and 0.082 h(-1); and
      intercompartmental k(pc) rate constants about 3.9 x 10(-4), and 0.016 and 8.9 x
      10(-6) h(-1) for lymphocytes, B cells, and T cells, respectively. The inhibition
      concentration IC(50) was about 0.48 microg/l for all cells, which was remarkably
      low. The apparent distribution volumes of peripheral pool (V(p)) were markedly
      larger than blood volume (V(b)) for all cells. The I(max) for cell trafficking
      was achieved at doses smaller than that producing graft protection, indicating
      stronger central than peripheral effects of this drug. The profound cell
      trafficking effects of FTY720 can be readily captured and interpreted with an
      extended indirect response model.

PMID- 11961051
TI  - Dynorphin A(1-17)-induced feeding: pharmacological characterization using
      selective opioid antagonists and antisense probes in rats.
AB  - Ventricular administration of the opioid dynorphin A(1-17) induces feeding in
      rats. Because its pharmacological characterization has not been fully identified,
      the present study examined whether a dose-response range of general and selective
      opioid antagonists as well as antisense oligodeoxynucleotide (AS ODN) opioid
      probes altered daytime feeding over a 4-h time course elicited by dynorphin.
      Dynorphin-induced feeding was significantly reduced by a wide range of doses (5
      80 nmol i.c.v.) of the selective kappa(1)-opioid antagonist nor-binaltorphamine.
      Correspondingly, AS ODN probes directed against either exons 1 and 2, but not 3
      of the kappa-opioid receptor clone (KOR-1) reduced dynorphin-induced feeding,
      whereas a missense oligodeoxynucleotide control probe was ineffective.
      Furthermore, AS ODN probes directed against either exons 1 or 2, but not 3 of the
      kappa(3)-like opioid receptor clone (KOR-3/ORL-1) also attenuated dynorphin
      induced feeding. Although the selective mu-antagonist beta-funaltrexamine (20-80
      nmol) reduced dynorphin-induced feeding, an AS ODN probe directed only against
      exon 1 of the mu-opioid receptor clone was transiently effective. Neither general
      (naltrexone, 80 nmol) nor delta (naltrindole, 80 nmol)-selective opioid
      antagonists were particularly effective in reducing dynorphin-induced feeding,
      and an AS ODN probe targeting the individual exons of the delta-opioid receptor
      clone failed to significantly reduce dynorphin-induced feeding. These converging
      antagonist and AS ODN data firmly implicate the kappa(1)-opioid receptor and the
      KOR-1 and KOR-3/ORL-1 opioid receptor genes in the mediation of dynorphin-induced
      feeding.

PMID- 11961053
TI  - Biochemical and behavioral characterization of novel methylphenidate analogs.
AB  - As part of a project to develop treatment agents for cocaine abuse, (+/-)-threo
      methylphenidate (TMP) and 11 analogs were characterized biochemically and
      behaviorally to assess their potential as anti-cocaine medications. The compounds
      contained aryl and/or nitrogen substitutions, and/or replacement of the ester
      function by an alcohol or ether. All of the analogs, except for the N-methyl
      substituted compounds, showed increased inhibitory potency against (3)H-(-)-2
      beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1,5-naphthalenedisulfonate
      ([(3)H]WIN 35,428) ([(3)H]WIN) binding to the dopamine transporter, compared with
      TMP. In general, parallel results were obtained for inhibition of [(3)H]dopamine
      ([(3)H]DA) uptake. Although compounds with N-substitutions were proportionally
      less potent at blocking DA uptake than WIN binding (compared with the
      unsubstituted compounds), one such compound that was 6-fold more potent against
      [(3)H]WIN binding than [(3)H]DA uptake did not attenuate inhibition by cocaine of
      synaptosomal [(3)H]DA transport. The compounds were significantly less potent in
      displacing [(3)H]citalopram binding from the serotonin transporter. In cocaine
      discrimination studies in rats, all but two of the analogs (both N-substituted)
      completely generalized with the cocaine stimulus. Robust positive correlations
      were observed between potency in the drug discrimination assay and activity at
      the dopamine transporter, but not the serotonin transporter. When tested for
      their ability to alter cocaine discrimination, four of the analogs (three of
      which had N-substitutions and shallow dose-response curves as cocaine
      substitutes) actually enhanced cocaine discrimination, often at combined doses of
      cocaine and test compound that were inactive when given separately. Taken
      together, the results suggest that TMP analogs may have potential as substitution
      therapies for the treatment of cocaine abuse.

PMID- 11961054
TI  - Correlation of neurokinin (NK) 1 receptor occupancy in gerbil striatum with
      behavioral effects of NK1 antagonists.
AB  - Interest in central neurokinin (NK) 1 receptors has increased based on reports of
      the therapeutic potential for NK1 antagonists in anxiety and depression. In these
      studies, an ex vivo binding procedure was used to correlate NK1 receptor
      occupancy in striatum by NK1 antagonists with their potency to inhibit NK1
      agonist-induced foot tapping in gerbils (GFT). The following compounds were
      administered orally: CP-99,994 [(+)-cis-n-[(2-methoxyphenyl)methyl]-2-phenyl-3
      piperidinamine), L-742,694 [5-[[2(S)-[[3,5-bis(trifluoromethyl)phenyl]methoxy]
      3(S)-phenyl-4-morpholinyl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one]), MK-869 [5
      [[2(R)-[1(R)-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3(S)-(4-fluorophenyl)-4
      morpholinyl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one], CP-122,721 [cis-n-[[2
      methoxy-5-(trifluoromethoxy)phenyl]methyl]-2-phenyl-3-piperidinamine], L-760,735
      F [4-[[2(R)-[1(R)-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3(S)-(4-fluorophenyl)-4
      morpholinyl]methyl]-N,N-dimethyl-1H-1,2,3-triazole-5- methanamine], GR205171 [N
      [[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]phenyl]methy]-2(S)-phenyl
      3(S)-piperidinamine], L-733,060 [(2S,3S)3-([3,5-bis(trifluoro
      methyl)phenyl]methoxy)-2-phenylpiperidine], and L-733,061 [(2R,3R)-3-([3,5
      bis(trifluoromethyl)phenyl]methoxy)-2-phenylpiperidine]. Two hours later, gerbils
      received the NK1 agonist GR73632 [H(2)N-(CH(2))(4)-CO-Phe-Pro-NMe-Leu-Met-NH(2)]
      i.c.v. and foot tapping was measured for 5 min. The same procedure was used for
      ex vivo binding studies except that saline, rather than agonist, was administered
      i.c.v. before dissection of the striatum. The tissue homogenate was then used in
      an equilibrium radioligand binding assay. When IC(50) values for inhibition of ex
      vivo (125)I-substance P binding by NK1 antagonists were compared with the
      corresponding EC(50) values for inhibition of GFT, a significant positive
      correlation was observed (r(2) = 0.97, p < 0.001). This result indicates that
      increased NK1 receptor occupancy in striatum by NK1 antagonists parallels the
      inhibition of agonist-mediated GFT. For all compounds, the dose that produced the
      maximum inhibition of GFT resulted in less than 100% ex vivo receptor occupancy
      in striatum. When gerbils did not receive the i.c.v. saline injection before ex
      vivo binding, thereby leaving the blood-brain barrier (BBB) intact, the IC(50)
      values for antagonists were unchanged, suggesting that potential damage to the
      BBB caused by the i.c.v. injection did not affect determinations of antagonist
      potency in the GFT model.

PMID- 11961055
TI  - Enhancement of glutathione cardioprotection by ascorbic acid in myocardial
      reperfusion injury.
AB  - The present experiment determined the effects of glutathione and ascorbic acid,
      the two most important hydrophilic antioxidants, on myocardial ischemia
      reperfusion injury and evaluated their relative therapeutic values. Isolated rat
      hearts were subjected to ischemia (30 min) and reperfusion (120 min) and treated
      with ascorbic acid, glutathione monoethyl ester (GSHme), or their combination at
      the onset of reperfusion. Administration of 1 mM GSHme alone, but not 1 mM
      ascorbic acid alone, significantly attenuated postischemic injury (P < 0.05
      versus vehicle). Most interestingly, coadministration of ascorbic acid with GSHme
      markedly enhanced the protective effects of GSHme (P < 0.01 versus vehicle). The
      protection exerted by the combination of GSHme and ascorbic acid at 1 mM each was
      significantly greater than that observed with 1 mM GSHme alone (P < 0.05).
      Moreover, treatment with GSHme alone or GSHme plus ascorbic acid markedly reduced
      myocardial nitrotyrosine levels, suggesting that these treatments attenuated
      myocardial peroxynitrite formation. These results demonstrated that 1) GSHme, but
      not ascorbic acid, exerted protective effects against ischemia-reperfusion
      injury; and 2) the protective effects of GSHme were further enhanced by
      coadministration with ascorbic acid, suggesting a synergistic effect between
      GSHme and ascorbic acid.

PMID- 11961056
TI  - Tissue expression, ontogeny, and inducibility of rat organic anion transporting
      polypeptide 4.
AB  - To date, organic anion transporting polypeptide 4 (Oatp4; Slc21a10) is known as a
      liver-specific and sodium-independent transporter that mediates transport of a
      variety of compounds. The purpose of this study was to determine whether Oatp4
      mRNA expression is specific to the liver compared with Oatp1, 2, 3, or 5. In
      addition, the effect of gender and age was determined by assessing the expression
      of Oatp4 mRNA during the postnatal development of rats. Furthermore, to determine
      whether Oatp4 gene expression is coordinately modulated by drug-metabolizing
      enzyme inducers, male rats were administered chemicals known to induce the
      expression of drug-metabolizing enzymes through six mechanisms: the aryl
      hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor,
      peroxisome proliferator-activated receptor, electrophile response element, or
      CYP2E1 inducers. The levels of Oatp1, 2, 3, 4, and 5 mRNA were measured using the
      branched DNA signal amplification technique. The tissue distribution of Oatp4 was
      almost exclusively expressed in liver in contrast to Oatp1, 2, 3, and 5. The
      hepatic expression of Oatp4 was low in newborn rats and increased gradually to
      the adult level with no significant difference between genders. The expression of
      Oatp4 was not consistently induced by any of the six groups of enzyme inducers.
      These findings continue to suggest that Oatp4 is expressed specifically in the
      liver. The preference of Oatp4 for endogenous compounds coupled with its
      refractory response to known drug-metabolizing enzyme inducers suggests that
      Oatp4 may be largely responsible for the homeostasis of endogenous rather than
      exogenous chemicals, including pharmaceuticals.

PMID- 11961057
TI  - A synthetic isoquinoline alkaloid, 1-(beta-naphthylmethyl)-6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinoline (YS 51), reduces inducible nitric oxide synthase
      expression and improves survival in a rodent model of endotoxic shock.
AB  - In the present study, the effects of 1-(beta-naphthylmethyl)-6,7-dihydroxy
      1,2,3,4-tetrahydroisoquinoline (YS 51), a positional isomer of 1-(alpha
      naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (YS 49), on nitric
      oxide production and inducible nitric oxide synthase (iNOS) mRNA expression were
      investigated in RAW 264.7 cells, mouse monocyte macrophage, exposed to
      lipopolysaccharide (LPS) plus interferon (IFN)-gamma. In addition, the effects of
      YS 51 on vascular reactivity in vitro and ex vivo, iNOS protein expression (rat
      lung) and survival rate (mice), were also investigated in LPS-treated rodents.
      Treatment with YS 51 reduced not only nitric oxide production (IC(50), 23.5
      microM), but also expression of iNOS mRNA in RAW 264.7 cells in a concentration
      dependent manner. Incubation of rat endothelium-denuded thoracic aorta with LPS
      (300 ng/ml) for 8 h in vitro resulted in suppression of vasoconstrictor effects
      to phenylephrine, which was restored by coincubation with YS 51. Treatment with
      YS 51 before (30 min) injection of LPS resulted in significant reduction of the
      expression of iNOS protein in rat lung tissue and restored the vascular
      contractility to 9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F(2alpha)
      (U46619), ex vivo. The plasma concentration of nitrite/nitrate (NOx) level was
      significantly (p < 0.01) reduced by YS 51 (10 and 20 mg/kg, i.p) in LPS-treated
      (10 mg/kg, i.p) rats. Furthermore, YS 51 significantly increased the survival
      rate in LPS-injected mice. In RAW 264.7 cells, YS 51 inhibited the formation of
      nuclear factor-kappaB-DNA complex and iNOS promoter activity in a concentration
      dependent manner, indicating that iNOS gene expression was modified
      transcriptionally by YS 51. These data strongly suggest that YS 51, a positional
      isomer of YS 49, might be beneficial in septic shock and/or endotoxin-induced
      inflammatory disorders.

PMID- 11961059
TI  - Short- and long-term influences of heavy metals on anionic drug efflux from renal
      proximal tubule.
AB  - We recently demonstrated in isolated killifish renal proximal tubules that two
      classes of nephrotoxicants, aminoglycoside antibiotics and radiocontrast agents,
      rapidly decrease transport mediated by multidrug resistance protein 2 (Mrp2) by
      causing endothelin (ET) release and signaling through an ET(B) receptor and
      protein kinase C (PKC). In the present study, we used killifish proximal tubules,
      fluorescein methotrexate, a fluorescent model substrate for Mrp2, and confocal
      microscopy to examine the effects of two heavy metal salts (CdCl(2) and HgCl(2))
      on Mrp2 function. Three patterns of effects were seen. First, exposing tubules to
      10 microM CdCl(2) or 100 nM HgCl(2) for 30 min reduced Mrp2-mediated transport.
      This reduction was abolished by the ET(B) receptor antagonist, RES-701-1, and by
      the PKC-selective inhibitor, bis-indolylmaleimide I; neither of these
      pharmacological tools by itself affected transport. As with aminoglycoside
      antibiotics and radiocontrast agents, the acute effects of 10 microM CdCl(2) or
      100 nM HgCl(2) on transport were also blocked by nifedipine, suggesting that
      Ca(2+) also initiated cadmium and mercury action. Second, exposure to higher
      concentrations of CdCl(2) and HgCl(2) appeared to be toxic. Third, exposing
      tubules for 6 to 24 h to lower levels of CdCl(2) increased Mrp2-mediated
      transport and Mrp2 immunostaining at the luminal membrane of the proximal tubule
      cells. Together, these findings indicate that exposure of renal proximal tubules
      to heavy metals initially leads to reduced Mrp2 function but is followed by an
      induction in Mrp2-mediated transport after long-term exposure.

PMID- 11961058
TI  - Bryostatin 1 increases 1-beta-D-arabinofuranosylcytosine-induced cytochrome c
      release and apoptosis in human leukemia cells ectopically expressing Bcl-x(L).
AB  - The ability of the protein kinase C down-regulator bryostatin 1 to potentiate 1
      beta-D-arabinofuranosylcytosine (ara-C)-induced apoptosis was examined in human
      leukemia cells (U937) over-expressing the antiapoptotic protein Bcl-x(L).
      Coadministration of bryostatin 1 with ara-C resulted in enhanced cytosolic
      release of cytochrome c and Smac/DIABLO, procaspase-3 and -9 activation, loss of
      mitochondrial membrane potential (Deltapsi(m)), poly(ADP-ribosyl)phosphorylase
      degradation, apoptosis, and loss of clonogenic survival in U937/Bcl-x(L) cells,
      although effects were not as marked as in empty-vector control cells. Whereas the
      broad caspase inhibitor ZVAD-fluoromethyl ketone blocked ara-C/bryostatin 1
      mediated caspase activation, loss of Deltapsi(m, )and apoptosis in U937 cells, it
      failed to diminish cytochrome c release. In contrast, ectopic expression of Bcl
      x(L) blocked cytochrome c redistribution as well as all other events involved in
      ara-C/bryostatin 1-mediated apoptosis. The ability of ectopic expression of
      cytokine response modifier A to attenuate, albeit partially, bryostatin 1
      mediated potentiation of ara-C-related apoptosis suggested a contributory role
      for activation of the extrinsic pathway in this phenomenon. Finally, the F(0)F(1)
      ATPase inhibitor oligomycin effectively blocked cytochrome c release as well as
      loss of Deltapsi(m) and apoptosis in U937/Bcl-x(L) cells. Together, these
      findings support the concept that bryostatin 1 potentiates ara-C lethality in
      human leukemia cells ectopically expressing Bcl-x(L) by diminishing the capacity
      of this antiapoptotic protein to antagonize cytochrome c release. In addition,
      they raise the possibility that activation of caspase cascades operating
      independently of Bcl-x(L)-associated mitochondrial actions may also contribute to
      enhanced lethality.

PMID- 11961060
TI  - Intestinal metabolism promotes regional differences in apical uptake of
      indinavir: coupled effect of P-glycoprotein and cytochrome P450 3A on indinavir
      membrane permeability in rat.
AB  - The purpose of this study was to investigate transport and metabolism
      contributions to low indinavir permeability in rat ileum and enhanced drug
      permeability in the jejunum. Permeability models utilized included single pass in
      situ rat intestinal perfusion and rat intestinal tissue mounted in Ussing
      chambers. Intestinal metabolism was measured by fractional appearance of
      metabolite (F(met)), determined as the percentage of the predominant metabolite
      M6 over luminal loss of indinavir in the perfusion model. Among the results,
      indinavir exhibited bidirectional transport across rat ileum. Verapamil and
      cyclosporin A inhibited net flux by 37 and 38%, respectively. Intestinal
      metabolism of indinavir was most significant in upper jejunum (F(met) = 65.78 +/-
      19.02%), decreasing in midjejunum (F(met) = 31.58 +/- 5.63%). M6 was not
      detectable in ileum or colon. Western blot analysis of rat intestinal mucosal
      tissue samples confirmed that the axial expression of CYP3A was consistent with
      the regional pattern of formation of M6. Intestinal metabolism was saturable and
      could be inhibited by the CYP3A inhibitor, ketoconazole. A low luminal
      concentration of indinavir (1 microM) was associated with high F(met) (87.90 +/-
      14.30%), whereas a high luminal concentration of indinavir (50 microM) was
      associated with low F(met) (35.84 +/- 11.59%). In the presence of ketoconazole,
      both F(met) and permeability of indinavir were reduced in the jejunum. These
      results suggest that 1) intracellular metabolism of indinavir enhances apical
      uptake of indinavir in the rat jejunum as a function of the increased
      concentration gradient generated across the epithelial cell membrane and 2) the
      efflux transporter P-glycoprotein limits apical uptake of indinavir in the ileum,
      resulting in low apparent permeability.

PMID- 11961061
TI  - Accelerated metabolism of nicotine and cotinine in pregnant smokers.
AB  - Cigarette smoking is the foremost modifiable risk factor for adverse pregnancy
      outcomes. Nicotine is a suspected fetal neuroteratogen. There is concern that
      nicotine may achieve toxic levels during pregnancy if nicotine replacement
      therapies are prescribed at doses used in the nonpregnant state. Ten healthy,
      volunteer, pregnant smokers received infusions of deuterium-labeled nicotine and
      cotinine during pregnancy and again postpartum. From blood and urine
      measurements, the following were determined: clearance (renal and nonrenal) of
      nicotine and cotinine, clearance of nicotine via the cotinine pathway (an
      indicator of CYP2A6 activity), and daily intake of nicotine from smoking. The
      clearance of nicotine and cotinine was significantly higher (60 and 140%,
      respectively), and the half-life of cotinine was much shorter (8.8 versus 16.6 h,
      P < 0.01) during pregnancy. Although plasma levels of cotinine were lower during
      pregnancy (119 versus 202 ng/ml, P < 0.05), daily intake of nicotine from smoking
      was similar during pregnancy and postpartum. For a given level of intake, the
      pharmacologic and toxicologic effects of nicotine during pregnancy are
      anticipated to be less than expected from nicotine metabolism data in nonpregnant
      women. Our data indicate that no downward dose adjustment needs to be made for
      nicotine replacement therapy during pregnancy. Conversely, higher than usual
      doses of nicotine may be necessary to optimize efficacy. Lower cotinine levels
      observed during pregnancy do not necessarily reflect less smoke exposure, and cut
      off levels used to classify nonsmokers, passive smokers, and active smokers need
      to be established for pregnancy.

PMID- 11961063
TI  - Enhanced neuroprotective effects of basic fibroblast growth factor in regional
      brain ischemia after conjugation to a blood-brain barrier delivery vector.
AB  - Basic fibroblast growth factor (bFGF) has minimal pharmacological effects in the
      central nervous system in the absence of blood-brain barrier (BBB) disruption.
      BBB transport of bFGF occurs via an absorptive-mediated transcytosis mechanism,
      which is relatively inefficient. To enhance the BBB transport of bFGF, this
      neurotrophin was reformulated to enable receptor-mediated transport across the
      BBB via the transferrin receptor. bFGF was monobiotinylated and coupled to a BBB
      drug-delivery vector comprised of streptavidin (SA) and the OX26 monoclonal
      antibody to the rat transferrin receptor. The entire conjugate of biotinylated
      bFGF bound to the OX26-SA is designated bio-bFGF/OX26-SA. The bFGF retains
      receptor-binding affinity and has increased brain uptake following conjugation to
      OX26-SA. The bio-bFGF/OX26-SA conjugate protects cortical cell cultures against
      hypoxia/reoxygenation insult in a dose-dependent manner in vitro. A single
      intravenous injection of bio-bFGF/OX26-SA, equivalent to a dose of 25 microg/kg
      bFGF, produces an 80% reduction in infarct volume in the brain of rats subjected
      to permanent occlusion of the middle cerebral artery in parallel with a
      significant improvement of neurologic deficit. The neuroprotection is time
      dependent, and there is a 67% reduction in stroke volume if the conjugate is
      administered at 60 min after arterial occlusion, whereas no significant reduction
      in stroke volume is observed if treatment is delayed 2 h. In conclusion,
      neuroprotection in regional brain ischemia is possible following the delayed
      intravenous injection of low doses of bFGF providing the neurotrophin is
      conjugated to a BBB drug-targeting system.

PMID- 11961062
TI  - Inhibition of cAMP accumulation by kappa-receptor activation in isolated iris
      ciliary bodies: role of phosphodiesterase and protein kinase C.
AB  - The present study was designed to examine the roles of protein kinase C (PKC) and
      phosphodiesterase (PDE) in modulating the action of kappa receptor stimulation on
      cAMP accumulation in isolated iris-ciliary bodies (ICBs) of New Zealand White
      rabbits. The kappa receptor agonist, (+/-)-1-(3,4-dichlorophenyl)acetyl-2-(1
      pyrrolidinyl)methylpiperidine (BRL-52537) (BRL), and the PKC activator, phorbol
      12,13-dibutyrate (PDBu), both caused a concentration-dependent inhibition of
      forskolin-stimulated cAMP production. The inhibitory effect of BRL on cAMP levels
      was significantly reduced in the presence of the selective kappa receptor
      antagonist, norbinaltorphimine (10(-6) M), but the effect of PDBu was not, thus
      supporting the involvement of kappa-opioid receptors in the response to BRL. In
      the presence of 3-isobutyl-1-methylxanthine or rolipram (10(-5) M), the
      inhibitory effect of BRL or PDBu (10(-6) M) on cyclic AMP accumulation was
      abolished. In the presence of the selective PKC antagonist, chelerythrine (10(-6)
      M), the inhibitory effect of PDBu or BRL (10(-6) M) was significantly reduced.
      Direct measurement of PDE activity demonstrated the ability of BRL and PDBu (10(
      6) M) to augment the activity of these enzymes. Preincubation of ICBs with
      rolipram (10(-5) M) or chelerythrine (10(-6) M) caused significant reversal of
      both BRL- and PDBu-induced increases in PDE activity. These results indicate that
      stimulation of PKC and PDE4 activity is part of the complex mechanism whereby
      kappa-opioid receptor agonists reduce levels of cAMP in the rabbit ICB. This
      mechanism of action could contribute to the ability of kappa-opioid agonists to
      suppress aqueous flow rate and to lower intraocular pressure.

PMID- 11961064
TI  - Differential actions of peripheral corticotropin-releasing factor (CRF),
      urocortin II, and urocortin III on gastric emptying and colonic transit in mice:
      role of CRF receptor subtypes 1 and 2.
AB  - Peripheral CRF inhibits gastric emptying and stimulates colonic motor function in
      rats. We investigated the role of CRF(1) and CRF(2) receptors in i.p. CRF-induced
      alterations of gut transit in conscious mice using selective CRF(1) and CRF(2)
      ligands injected i.p. Gastric emptying 2 h after ingestion of a solid chow meal
      and colonic transit (time to expel a bead inserted into the distal colon) were
      determined simultaneously. Rat/human (r/h)CRF, which has CRF(1) > CRF(2) binding
      affinity, decreased distal colonic transit time at lower doses (6-12 microg/kg)
      than those inhibiting gastric emptying (20-60 microg/kg). Ovine CRF, a
      preferential CRF(1) receptor agonist (6-60 microg/kg), reduced significantly the
      colonic transit time without altering gastric emptying, whereas the selective
      CRF(2) receptor agonists mouse urocortin II (20-60 microg/kg) and urocortin III
      (120 microg/kg) inhibited significantly gastric emptying without modifying
      colonic transit. The CRF(1)/CRF(2) receptor antagonist, astressin (30-120
      microg/kg), dose dependently prevented r/hCRF (20 microg/kg)-induced inhibition
      of gastric emptying and reduction of colonic transit time. The selective CRF(1)
      receptor antagonists, NBI-27914 (C(18)H(20)Cl(4)N(4)C(7)H(8)O(3)S) and CP-154,526
      (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4
      yl]ethylamine) (5-30 mg/kg), dose dependently blocked r/hCRF action on the colon
      without influencing the gastric response, whereas the CRF(2) receptor antagonist,
      antisauvagine-30 (30-100 microg/kg), dose dependently abolished r/hCRF-induced
      delayed gastric emptying and had no effect on colonic response. These data show
      that i.p. r/hCRF-induced opposite actions on upper and lower gut transit in
      conscious mice are mediated by different CRF receptor subtypes: the activation of
      CRF(1) receptors stimulates colonic propulsive activity, whereas activation of
      CRF(2) receptors inhibits gastric emptying.

PMID- 11961065
TI  - A new family of thromboxane receptor antagonists with secondary thromboxane
      synthase inhibition.
AB  - We report herein a novel class of thromboxane receptor (TP receptor) antagonists
      modeled on unstable natural lipids that we identified several years ago, the
      hepoxilins. These antagonists have been rendered chemically and biologically more
      stable than the natural compounds through structural modification by chemical
      synthesis. We demonstrate that the analogs inhibit the aggregation of human
      platelets in vitro evoked by the thromboxane receptor agonists, I-BOP ([1S
      [1alpha,2alpha(Z),3beta(1E,3S*),4alpha]]-7-[3-[3-hydroxy-4-(4-iodophenoxy)-1
      butenyl]-7-oxabi-cyclo[2.2.1]hept-2-yl]5-heptenoic acid) and U46619 (9,11-dideoxy
      9alpha,11alpha-methanoepoxy-prosta-5Z,13E-dien-1-oic acid). The most potent of
      the analogs described, PBT-3 [10(S)-hydroxy-11,12-cyclopropyl-eicosa-5Z,8Z,14Z
      trienoic acid methyl ester], has an IC(50) versus aggregation by I-BOP = 0.6 x
      10(-7) M and versus U46619 = 7 x 10(-7) M, representing one of the most potent
      anti-aggregating substances so far described. PBT-3 also inhibits thromboxane
      formation and aggregation evoked by collagen with an IC(50) = 8 x 10(-7) M. Other
      PBT (hepoxilin cyclopropane) analogs so far tested were 5- to 10-fold less
      active, and the native hepoxilins were about 500-fold less active. Neither PBT-3
      nor the other analogs inhibited 12-lipoxygenase, phospholipase A(2), or
      cyclooxygenase 1 or 2, and weakly stimulated adenyl cyclase (threshold
      stimulation at 10(-7) M and little selectivity for each of the PBT compounds). TP
      antagonism by PBT-3 was further demonstrated in receptor binding studies through
      use of (125)I-BOP, where the IC(50) for PBT-3 was 8 x 10(-9) M, approximately 16
      fold less than for I-BOP itself. These findings identify a new mode of action of
      PBT-3 and other related analogs as primarily TP antagonists. These studies
      identify a new family of compounds useful in further development as novel
      therapeutics for thromboxane-mediated diseases.

PMID- 11961066
TI  - Geraniol, a component of plant essential oils, sensitizes human colonic cancer
      cells to 5-Fluorouracil treatment.
AB  - Differentiation of human colonic cancer cells at confluency has been correlated
      to their increased resistance to chemotherapeutic agents. The aim of this study
      was to determine whether blocking Caco-2 cell differentiation could sensitize the
      cells to 5-fluorouracil (5-FU) treatment. We show that in cells at confluency,
      geraniol (400 microM) prevented the formation of brush-border membranes and
      inhibited the expression of intestinal hydrolases (sucrase, lactase, alkaline
      phosphatase). The antiproliferative effect of geraniol (400 microM) together with
      5-FU (5 microM) was twice that of 5-FU alone. The cytotoxicity induced by 5-FU
      was enhanced in the presence of geraniol, as shown by a 50% increase of lactate
      dehydrogenase release in the culture medium. These effects are related to
      enhanced intracellular accumulation of 5-FU in the presence of geraniol as shown
      by a 2-fold increase in intracellular 5-[6-(3)H]FU (1.5 microCi/ml). It is
      concluded that geraniol sensitizes colonic cancer cells to 5-FU treatment, by
      increasing the cytotoxicity of the drug, and that this results from the
      facilitated transport of 5-FU and the blockade of the morphological and
      functional differentiation of the cancer cells.

PMID- 11961067
TI  - Nongenomic regulation of the kinetics of exocytosis by estrogens.
AB  - The role of nongenomic action of estrogens on elicited catecholamine secretion
      and exocytosis kinetics was studied in perfused rat adrenals and in cultured
      bovine chromaffin cells. 17beta-Estradiol as well as the estrogen receptor
      modulators raloxifene and LY117018, but not 17alpha-estradiol, inhibited at the
      micromolar range the catecholamine output elicited by acetylcholine or high
      potassium. However, these agents failed to modify the secretion elicited by high
      Ca(2+) in glands treated with the ionophore A-23187 (calcimycin), suggesting that
      estrogens did not directly act on the secretory machinery. At the single cell
      level, estrogens modified the kinetics of exocytosis at nanomolar range. All of
      the drugs tested except 17alpha-estradiol produced a profound slowing down of the
      exocytosis as measured by amperometry. LY117018 also reduced the granule content
      of catecholamines. 17beta-Estradiol reduced the intracellular free Ca(2+) but
      only at micromolar concentrations, whereas nanomolar concentrations increased the
      cAMP levels. These effects were reproduced with the nonpermeable drug 17beta
      estradiol-horseradish peroxidase and antagonized with nanomolar concentrations of
      the antiestrogen ICI 182,780 (fulvestrant). Our data suggest the presence of
      membrane sites that regulate both the exocytotic phenomenon and the total
      catecholamine release with high and low affinity, respectively.

PMID- 11961068
TI  - Conjugates of nucleoside analogs with lactosaminated human albumin to selectively
      increase the drug levels in liver blood: requirements for a regional
      chemotherapy.
AB  - Nucleoside analogs (NAs) conjugated with galactosyl terminating peptides
      selectively enter hepatocytes via the asialoglycoprotein receptor and, after
      intracellular release from the carrier, partly exit from these cells into the
      bloodstream, resulting in higher concentrations in liver blood than in systemic
      circulation. Therefore, conjugates of anticancer NAs can be exploited to
      accomplish a loco-regional noninvasive treatment of liver micrometastases. In the
      present experiments we studied whether the enhancement of drug levels in liver
      blood achieved when NAs are given in the coupled form depends on the rate of drug
      elimination from the bloodstream. Three NAs, adenine arabinoside (ara-A), 5
      fluoro-2'-deoxyuridine (FUdR), and 2',2'-difluorodeoxycytidine, were coupled with
      lactosaminated human albumin, a galactosyl terminating carrier. In rats that
      received an intravenous bolus injection of these conjugates, we compared the drug
      concentrations in liver blood to those in the systemic circulation. We found that
      enhanced levels of NAs in liver blood were only achieved by administering the
      conjugates of the drugs (ara-A and FUdR), which are rapidly cleared from the
      bloodstream. Increased drug levels also were obtained when ara-A and FUdR
      conjugates were slowly infused (a way of administration often used for anticancer
      drugs). The experiments also showed that galactosyl terminating conjugates of NAs
      might have the potential to produce a therapeutic effect only when the coupled
      drugs are active at low blood concentrations, since the amounts of drugs
      introduced into hepatocytes and released by these cells in the bloodstream cannot
      be increased when the receptor for the hepatic uptake of galactosyl terminating
      peptides is saturated.

PMID- 11961069
TI  - Muscarinic receptor knockout mice: role of muscarinic acetylcholine receptors
      M(2), M(3), and M(4) in carbamylcholine-induced gallbladder contractility.
AB  - Muscarinic receptors play a major role in gallbladder function, although the
      muscarinic receptor(s) mediating smooth muscle contractility is unclear. This
      study compared smooth muscle contractile responses to carbamylcholine (10(-7)-10(
      3) M) in isolated gallbladder from wild-type and M(2), M(3), and M(4) receptor
      knockout mice. Carbamylcholine-induced contraction in gallbladder was associated
      with tachyphylaxis and the release of a cyclooxygenase product because
      indomethacin (10(-6) M) inhibited carbamylcholine-induced contraction. The M(3)
      receptor was the major muscarinic receptor involved in contraction because
      carbamylcholine-induced contractility was inhibited in gallbladder from M(3)
      receptor knockout mice. Furthermore, the muscarinic receptor antagonists 11-[[[2
      diethylamino-O-methyl]-1-piperidinyl]acetyl]-5,11-dihydrol-6H-pyridol[2,3
      b][1,4]benzodiazepine-6-one (AF-DX 116) and pirenzepine dextrally shifted
      contraction to carbamylcholine in gallbladder from wild-type, M(2), and M(4)
      receptor knockout mice, with affinities consistent with M(3) receptor
      interaction. In addition, maximal contraction to carbamylcholine was reduced in
      gallbladder from M(2) receptor knockout mice and affinities for AF-DX 116 and
      pirenzepine in gallbladder from M(3) receptor knockout mice were consistent with
      their affinities at M(2) receptors. In M(4) receptor knockout mice, contraction
      to carbamylcholine was dextrally shifted, although the affinities for AF-DX 116
      and pirenzepine in gallbladder from M(2) or M(3) knockout mice were not similar
      to their affinities at M(4) receptors. The M(4) receptor may serve as an
      accessory protein necessary for optimal potency of M(2) and M(3) receptor
      mediated responses. Thus, muscarinic receptor knockout mice provided direct and
      unambiguous evidence that M(3), and to a lesser extent, M(2) receptors are the
      predominant muscarinic receptors mediating gallbladder contractility, and M(4)
      receptors appear necessary for optimal potency of carbamylcholine in gallbladder
      contraction.

PMID- 11961071
TI  - Agonist, antagonist, and inverse agonist characteristics of TIPP (H-Tyr-Tic-Phe
      Phe-OH), a selective delta-opioid receptor ligand.
AB  - Recent evidence indicates that the well established delta-opioid antagonist TIPP
      (H-Tyr-Tic-Phe-Phe-OH) also displays agonist activity in several cellular models.
      Therefore, it is possible that TIPP, and structurally related compounds, might
      represent a novel class of opioid agonists exhibiting unique characteristics. The
      purpose of this study was to examine the properties of TIPP at selected points of
      the signal transduction pathway (i.e., receptor binding, G-protein activation,
      and effector regulation) in GH(3)DORT cells (GH(3) cells expressing delta-opioid
      receptors) and compare them with that of an established delta-opioid agonist, [D
      Pen(2),D-Pen(5)]-enkephalin (DPDPE). DPDPE exhibited properties of an agonist in
      all assays. In contrast, TIPP demonstrated characteristics of an agonist,
      antagonist, or inverse agonist, depending on the step in the signal transduction
      cascade examined and the assay conditions employed. In receptor binding assays,
      the addition of guanine nucleotides and sodium ions increased the affinity of
      TIPP for delta-opioid receptors in both membrane preparations and digitonin
      permeabilized cells, which is characteristic of an inverse agonist. In assays
      measuring G-protein activation, TIPP failed to stimulate guanosine 5'-O-(3
      [(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding in membrane preparations,
      which is consistent with an antagonist profile. However, when using cells semi
      permeabilized with digitonin, TIPP exhibited properties of an agonist, producing
      concentration-dependent, antagonist-reversible stimulation of [(35)S]GTPgammaS
      binding. Finally, in assays examining regulation of the intracellular effector
      adenylyl cyclase, TIPP exhibited characteristics of an agonist, producing
      inhibition of enzyme activity in both membrane preparations and whole cells.
      Therefore, although DPDPE and TIPP act similarly as agonists to regulate the
      intracellular effector adenylyl cyclase, they demonstrate significant differences
      in the signal transduction cascade preceding this final point of convergence.

PMID- 11961070
TI  - Characterization of nicotinic agonist-induced [(3)H]dopamine release from
      synaptosomes prepared from four mouse brain regions.
AB  - The inhibition of uptake of [(3)H]dopamine into synaptosomes prepared from four
      mouse brain regions was investigated. The inhibition curves demonstrated that in
      three regions, striatum, nucleus accumbens, and olfactory tubercle,
      [(3)H]dopamine was taken up exclusively by dopaminergic terminals. In frontal
      cortex, however, only a portion of the uptake was into dopaminergic terminals,
      with a larger amount taken up by noradrenergic terminals, and another small
      portion by serotonergic terminals. Release studies in frontal cortex indicated
      that in this region only dopaminergic and noradrenergic terminals are capable of
      packaging [(3)H]dopamine in a form allowing vesicle-mediated release;
      additionally, only the dopaminergic terminals have functional presynaptic nAChRs
      that, when stimulated by nicotinic agonists, evoke [(3)H]dopamine release.
      Agonist-stimulated [(3)H]dopamine release was characterized from synaptosomes
      prepared from four mouse brain regions. alpha-Conotoxin MII was a partial
      inhibitor of dopamine release in all of the brain regions, which suggests that a
      minimum of two nicotinic cholinergic receptors (nAChRs) are expressed in the
      nerve terminals of all four brain regions. No nicotine-induced [(3)H]dopamine
      release was detected in any brain region when the synaptosomes were prepared from
      beta2 null mutant mice, which indicates that the beta2 subunit is required for
      all nAChRs mediating this release. Dose-response curves were constructed for
      seven agonists in each of the brain regions. The pharmacological properties of
      synaptosomal [(3)H]dopamine release appear similar across the four brain regions.
      The results suggest that all four regions express the same nAChRs, although
      subtle regional differences may exist.

PMID- 11961072
TI  - Pharmacokinetic advantage of intrapericardially applied substances in the rat.
AB  - Intrapericardial application of therapeutic agents may open perspectives for
      target-directed therapy of the diseased heart. This study was performed to
      investigate whether intrapericardial drug application is beneficial from a
      pharmacokinetic point of view. Male Wistar rats were provided with
      intrapericardial and intravascular catheters for substance administration and
      sampling. Intrapericardial bolus injections of fluorescent macromolecules
      [fluorescein isothiocyanate (FITC)-rat IgG, molecular weight about 155 kDa; Texas
      Red rat serum albumin, mol. wt. 67 kDa; Texas Red fibroblast growth factor (FGF),
      mol. wt. 18 kDa; and FITC heparin, mean mol. wt. 18 kDa] resulted in substance
      concentrations in pericardial fluid that exceeded those in plasma, for several
      hours. Pericardial fluid volumes of catheter-instrumented rats, derived from
      (initial) central compartment volumes, ranged between 0.5 and 0.9 ml/kg. After
      chronic (7 days) intrapericardial infusions with osmotic minipumps, pericardial
      fluid/plasma concentration ratios (local advantages) were 7 to 10 for the
      fluorescent proteins and >30 for FITC-heparin. This can be explained by the low
      substance clearances in pericardial fluid compared with plasma. Local advantages
      of the small substances cortisol (mol. wt. = 362.5) and a carbonic acid
      derivative thereof (mol. wt. = 348) were 14 and 420. Intrapericardial infusion of
      (125)I-FGF-2 yielded 8 times higher cardiac tissue levels than systemic infusion,
      whereas (125)I-FGF-2 was found in the entire heart. Pharmacokinetic profiles of
      intrapericardially applied substances are such that desired local drug
      concentrations can be obtained at lower dosages, whereas systemic concentrations
      remain low (thus reducing the potential risk of peripheral side effects).
      Therefore, intrapericardial application of therapeutic agents provides a
      promising strategy for site-specific treatment of heart or coronary diseases.

PMID- 11961073
TI  - Resorcinol derivatives: a novel template for the development of cannabinoid
      CB(1)/CB(2) and CB(2)-selective agonists.
AB  - The role of the oxygen of the benzopyran substituent of Delta(9)
      tetrahydrocannabinol in defining affinity for brain cannabinoid (CB(1)) receptors
      is not well understood; however, it is known that opening the pyran ring can
      result in either increased potency and affinity, as in CP 55,940 [(-)-cis-3-[2
      hydroxy-4(1,1- dimethyl-heptyl)phenyl]-trans-4-(3-hydroxy-propyl)cyclohexanol],
      or in an inactive cannabinoid, as in cannabidiol. In the present study, a series
      of bicyclic resorcinols that resemble cannabidiol were synthesized and tested in
      vitro and in vivo. Analysis of the structure-activity relationships of these
      analogs revealed several structural features that were important for maintaining
      CB(1) receptor recognition and in vivo activity, including the presence of a
      branched lipophilic side chain and free phenols as well as substitution of a
      cyclohexane as the second ring of these bicyclic cannabinoids. Many of these
      analogs exhibited CB(2) selectivity, particularly the dimethoxyresorcinol
      analogs, and this selectivity was enhanced by longer side chain lengths. Hence,
      unlike cannabidiol, these resorcinol derivatives had good affinity for CB(1)
      and/or CB(2) receptors as well as potent in vivo activity. These results suggest
      that the resorcinol series represent a novel template for the development of
      CB(2)-selective cannabinoid agonists that have the potential to offer insights
      into similarities and differences between structural requirements for receptor
      recognition at CB(1) and CB(2) receptors.

PMID- 11961074
TI  - Relative reinforcing strength of three N-methyl-D-aspartate antagonists with
      different onsets of action.
AB  - The potential contribution of onset and duration of pharmacological action to the
      reinforcing strength of three intravenously delivered N-methyl-D-aspartate
      antagonists was evaluated in this study. The onsets and durations of action of
      ketamine, phencyclidine, and dizocilpine were evaluated by observation and
      tabulation of their behavioral effects in rhesus monkeys after i.v.
      administration. The reinforcing effects of each drug were tested in a paradigm in
      which the fixed ratio requirements for i.v. drug injection were increased
      systematically. The peak observable effect of ketamine occurred immediately after
      its administration. There were some immediately observable effects of
      phencyclidine, although the peak effect of phencyclidine was delayed for 3 to 10
      min. Dizocilpine had few immediate effects and a peak effect 32 min after
      administration. Ketamine had the shortest duration of action, followed by
      phencyclidine and dizocilpine. Analysis of demand curves and response output
      curves that were normalized to account for potency differences among the drugs
      revealed that ketamine and phencyclidine were equally effective as reinforcers,
      and they were both much stronger reinforcers than was dizocilpine. The data
      therefore suggest that a fast onset of action increases the reinforcing strength
      of drugs, although duration of action may play a role as well.

PMID- 11961075
TI  - Relative reinforcing effects of three opioids with different durations of action.
AB  - The role of duration of action on the relative reinforcing effects of three
      opioid drugs (fentanyl, alfentanil, and remifentanil) was evaluated. Duration and
      onset of action were determined using measures of respiratory depression and
      antinociception after i.v. administration. Effects on minute volume of
      respiration indicated that each of the three opioids had immediate onsets of
      action after i.v. administration. Fentanyl's duration of suppression of
      respiration and antinociception was longer than that of alfentanil, which was
      longer than that of remifentanil. Reinforcing strength was measured in i.v. self
      administration studies in which the fixed ratio resulting in drug administration
      was increased from one session to the next. Comparisons were made of the
      behavioral economic variables P(max) and area under the demand curve (O(max)).
      Remifentanil maintained higher rates of responding than did alfentanil, and
      alfentanil maintained higher rates of responding than did fentanyl. When
      normalized demand functions were compared, however, the drugs did not differ
      significantly from each other in terms of P(max) or O(max). These data agree with
      those of others who have suggested that duration of action is not an important
      contributor to drugs' reinforcing strength.

PMID- 11961076
TI  - P2Y(13): identification and characterization of a novel Galphai-coupled ADP
      receptor from human and mouse.
AB  - We have identified an orphan G protein-coupled receptor, SP174, that shares a
      high degree of homology with the recently described ADP receptor P2Y(12). mRNA
      for SP174 is abundant in the brain and in cells of the immune system. In the
      present study, we demonstrate that SP174 is also a receptor for ADP, which is
      coupled to Galphai. ADP potently stimulates SP174 with an EC(50) of 60 nM, and
      other related nucleotides are active as well, with a rank order of potency 2
      methylthio-ADP tetrasodium = adenosine 5'-O-2-(thio)diphosphate = 2-methylthio
      ATP tetrasodium > ADP > AP3A >ATP > IDP. This pharmacological profile is similar
      to that for P2Y(12). We have also identified the murine homolog of SP174, which
      exhibits 75% homology to the human receptor. ADP is also a potent agonist at the
      murine receptor, and its pharmacological profile is similar to its human
      counterpart, but ADP and related nucleotides are more potent at the murine
      receptor than the human receptor. In keeping with the general nomenclature for
      the purinergic receptors, we propose designating this novel receptor P2Y(13).

PMID- 11961077
TI  - Dual modulation of striatal acetylcholine release by hyperforin, a constituent of
      St. John's wort.
AB  - Extracts of the medicinal plant St. John's wort (Hypericum perforatum) are widely
      used for the treatment of mild to moderate depression. Hyperforin, a constituent
      of St. John's wort, is known to inhibit the sodium-dependent uptake of
      catecholamines and amino acids into synaptic nerve endings, probably by
      interference with mechanisms controlling the synaptic sodium concentration.
      Because de novo synthesis of acetylcholine (ACh) is dependent on sodium-dependent
      high-affinity choline uptake, we studied the effect of hyperforin on choline (Ch)
      uptake in vitro and on striatal ACh release in vivo using microdialysis. In rat
      brain synaptosomes, hyperforin inhibited high-affinity choline uptake with an
      IC(50) of 8.5 microM, whereas low-affinity uptake was not affected. Local
      infusion of hyperforin (100 microM) via the dialysis probe caused a delayed
      reduction of ACh release and a concomitant increase of Ch levels. Infusion of a
      lower concentration of hyperforin (10 microM), however, increased striatal ACh
      release and lowered Ch levels. Systemic administration of hyperforin (1-10 mg/kg
      i.p.) led to therapeutic plasma levels of hyperforin and caused a significant
      elevation of striatal ACh release. Behavioral testing revealed a reduction of
      locomotor activity in mice treated with high-dose (10 mg/kg) hyperforin. We
      conclude that low doses of hyperforin stimulate striatal ACh release by an
      unknown mechanism, whereas high doses inhibit synaptic choline uptake and ACh
      release. The results are discussed with respect to the therapeutic use of St.
      John's wort in patients with neurodegenerative disorders.

PMID- 11961078
TI  - Allosteric modulation of muscarinic receptor signaling: alcuronium-induced
      conversion of pilocarpine from an agonist into an antagonist.
AB  - Previous studies on allosteric interactions at muscarinic receptors have often
      focused on ligand-receptor binding interactions, because ligand binding seemed to
      reflect functional consequences. The prototypal allosteric agent alcuronium is
      known to bind with similar affinity to the M(2) subtype of muscarinic
      acetylcholine receptors whether or not the receptors are occupied by the agonist
      pilocarpine. To determine allosteric modulation of receptor signaling by
      alcuronium, the effects of pilocarpine were measured in contracting guinea pig
      left atria and on G-protein coupling in M(2)-transfected Chinese hamster ovary
      (CHO) cell membranes. Alcuronium dose-dependently suppressed pilocarpine-induced
      reduction of isometric contraction force in atria (pIC(50, Alc) = 5.63) without
      any effect on the EC(50) of pilocarpine, consistent with an allosteric mechanism.
      In contrast, alcuronium shifted the concentration-effect curve of the agonist
      oxotremorine M to the right without affecting the maximal effect, in a formally
      competitive manner (pK(A, Alc) = 5.54). If pilocarpine remained receptor bound in
      the presence of alcuronium, this indicates that pilocarpine can no longer act as
      an agonist. In support of this hypothesis, pilocarpine acted as a competitive
      antagonist against oxotremorine M in the presence of 10 microM alcuronium.
      Measuring guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding
      in CHO-M(2) membranes yielded similar results. Alcuronium suppressed pilocarpine
      induced stimulation of [(35)S]GTPgammaS binding (pIC(50, Alc) = 5.47) without
      shift in EC(50), whereas it competitively shifted the response to oxotremorine M
      (pK(A, Alc) = 5.97). [(3)H]Oxotremorine M binding data corresponded with the
      functional findings. In conclusion, alcuronium converted the agonist pilocarpine
      into an antagonist-a novel type of functional allosteric interaction.

PMID- 11961079
TI  - Subconductance activity induced by quinidine and quinidinium in purified cardiac
      sarcoplasmic reticulum calcium release channels.
AB  - This study examined the effects of quinidine, quinine, and the quaternary
      quinidine derivative, quinidinium, on the conductance and activity of purified
      cardiac sarcoplasmic reticulum calcium release channels/ryanodine receptors (RyR)
      incorporated into planar lipid bilayers. Quinidine (50-500 microM) reduced the
      single-channel open probability in a voltage- and concentration-dependent manner.
      Reduction of channel activity was evident only at positive holding potentials
      where current flow is from the cytoplasmic to luminal side of the channel and
      when the drug was present only on the cytoplasmic face of the channel. A more
      pronounced effect was the appearance of a subconductance state at positive
      potentials. Single channel recordings and dose-response experiments revealed that
      at least two quinidine molecules were involved in reduction of the RyR activity.
      The permanently charged quinidinium compound produced nearly identical effects as
      quinidine when present only on cytoplasmic side of the channel, suggesting the
      positive-charged form of quinidine is responsible for the effects on the channel.
      There was no stereospecificity in the effects of quinidine because the
      levoisomer, 100 microM quinine, produced a similar subconductance activity of the
      channel. Ryanodine modification of the channel prevented subconductance activity.
      These findings suggest that the quinidine-induced subconductance activity may be
      the result of a partial occlusion of the channel pore interfering with ion
      conduction. Modification of the channel by ryanodine alters quinidine binding to
      the channel through a conformational change in protein structure.

PMID- 11961080
TI  - Anti-inflammatory effects of a cyclosporine receptor-binding compound, D-43787.
AB  - By virtue of its binding to cyclophilin, the cellular receptor for cyclosporine
      (CsA), we could identify a new compound D-43787 [N-[(1-tert-butyloxycarbonyl)
      indolin-2-(S)-carbonyl]-indolin-2-(S)-carbonacid-[N-epsilon-benzyloxycarbonyl)-2
      (S)-lysin methylester]-amide] exhibiting immunomodulating properties. It
      inhibited cell proliferation induced by 12-O-tetradecanoylphorbol-13-acetate
      (TPA)/ionomycin and anti-CD3/CD28 with an IC(50) of 0.3 microM. The protein
      phosphatase calcineurin, which is the target of the CsA-cyclophilin complex, is
      not inhibited by D-43787. It inhibited T helper cell (Th) 2 cytokines interleukin
      (IL)-4, -5, and -13 more effectively than the Th1 cytokine interferon (IFN)-gamma
      in human primary T cells. The IC(50) for IL-5 and IL-13 in TPA/ionomycin
      stimulated peripheral blood mononuclear cells (PBMC) is 0.7 +/- 0.1 and 0.5 +/-
      0.1 microM, respectively, whereas the IC(50) for IFN-gamma is 2.0 +/- 0.4 microM.
      When PBMC were stimulated with anti-CD3/CD28, the IC(50) for IL-4, -5, and -13
      were 1.5 +/- 0.2, 1.8 +/- 0.2, and 1.9 +/- 0.4 microM, respectively. IFN-gamma
      was only partially inhibited under these conditions. This effect was even more
      pronounced in pure CD4(+) T cells. Pretreatment of human monocytes with D-43787
      inhibited lipopolysaccharide-induced proinflammatory cytokines IL-6 and TNFalpha
      with an IC(50) of 1.2 +/- 0.1 and 4.7 +/- 0.9 microM, respectively. In vivo, D
      43787 potently inhibited late-phase eosinophilia in actively sensitized and
      challenged guinea pigs (10 mg/kg, i.p.: 51%) and Brown-Norway rats (1 mg/kg,
      intrapulmonary: 66% 30 mg/kg, i.p.: 50%). In adjuvant-induced arthritis, D-43787
      (10-40 mg/kg, b.i.d., i.p.) dose dependently reduced edema development on both
      hind paws. The potency of D-43787 was comparable with that of indomethacin and
      dexamethasone. In conclusion, we characterized a novel Th2 selective
      immunosuppressive drug with possible anti-asthmatic/anti-inflammatory effects.
      Its mode of action is distinct from that of CsA.

PMID- 11961081
TI  - Pulmonary eosinophilia in a murine model of allergic inflammation is attenuated
      by small molecule alpha4beta1 antagonists.
AB  - Inhibition of alpha4beta1/vascular cell adhesion molecule-1 (VCAM-1) interactions
      have therapeutic potential in treating allergic airway disease because of the
      importance of these adhesion molecules in the trafficking of eosinophils,
      lymphocytes, and monocytes. We examined several small molecule inhibitors of
      alpha4beta1/VCAM-1 interactions with in vitro potencies (IC(50) values) ranging
      from 0.52 nM (CP-664511; 3-[3-(1-[2-[3-methoxy-4-(3-O-tolyl-ureido)phenyl]
      acetylamino]-3-methyl-butyl)isoxazol-5-yl]-propionic acid) to 38.5 nM (CP-609643;
      3-[3-methyl-1-[2-[4-(3-O-tolyl-ureido)-phenyl]-acetylamino]-butyl)-isoxazol-5-yl]
      propionic acid). The same compounds were evaluated in vivo using a murine model
      of ovalbumin-induced pulmonary eosinophilia. In this model, systemic
      administration of antibodies against alpha4 reduced bronchoalveolar lavage (BAL)
      eosinophilia approximately 60%. Small molecule alpha4beta1 antagonists were
      administered by intratracheal instillation and demonstrated dose-dependent
      inhibition of BAL eosinophil numbers and achieved a maximum inhibition of
      approximately 60%. In general, the rank order of potency for these compounds in
      vitro was consistent with that observed in vivo, which confirms that their
      efficacy is likely via blockade of alpha4beta1/VCAM-1 interactions. The most
      potent compound, CP-664511, also inhibited BAL eosinophilia following s.c.
      administration (1-10 mg/kg, s.c.). These data support the utility of small
      molecule alpha4beta1 antagonists in the treatment of relevant diseases, such as
      asthma.

PMID- 11961082
TI  - Propargylamines induce antiapoptotic new protein synthesis in serum- and nerve
      growth factor (NGF)-withdrawn, NGF-differentiated PC-12 cells.
AB  - (-)-Deprenyl and structurally related propargylamines increase neuronal survival
      independently of monoamine oxidase B (MAO-B) inhibition, in part by decreasing
      apoptosis. We found that deprenyl and two other propargylamines, one of which
      does not inhibit monoamine oxidase B, increased survival in trophically withdrawn
      6-day nerve growth factor (NGF)- and 9-day NGF-differentiated PC-12 cells but not
      in NGF naive or 3-day NGF-differentiated PC-12 cells. Four days of prior NGF
      exposure were required for the propargylamine-mediated antiapoptosis. Studies
      using actinomycin D, cycloheximide, and camptothecin revealed that the
      maintenance of both transcription and translation, particularly between 2 and 6 h
      after trophic withdrawal, was required for propargylamine-mediated antiapoptosis.
      Metabolic labeling of newly synthesized proteins for two-dimensional protein gel
      autoradiography and scintillation counting showed that the propargylamines either
      increased or reduced the levels of new synthesis or induced de novo synthesis of
      a number of different proteins, most notably proteins in the mitochondrial and
      nuclear subfractions. Western blotting for whole cell or subcellular fraction
      lysates showed that the timing of new protein synthesis changes or subcellular
      redistribution of apoptosis-related proteins induced by the propargylamines were
      appropriate to antiapoptosis. The apoptosis-related proteins included superoxide
      dismutases (SOD1 and SOD2), glutathione peroxidase, c-JUN, and glyceraldehyde-3
      phosphate dehydrogenase. Most notable were the prevention of apoptotic decreases
      in BCL-2 levels and increases in mitochondrial BAX levels. In general, (-)
      deprenyl-related propargylamines appear to reduce apoptosis by altering the
      levels or subcellular localization of proteins that affect mitochondrial membrane
      permeability, scavenge oxidative radicals, or participate in specific apoptosis
      signaling pathways.

PMID- 11961083
TI  - Enhanced inhibition of a mutant neuronal nicotinic acetylcholine receptor by
      agonists: protection of function by (E)-N-methyl-4-(3-pyridinyl)-3-butene-1-amine
      (TC-2403).
AB  - Inhibition of neuronal nicotinic receptors can be regulated by sequence in the
      beta subunit second transmembrane domain (TM2). The incorporation of a
      beta4(6'F10'T) subunit, which contains sequence from the muscle beta subunit at
      the TM2 6' and 10' positions of the neuronal beta4 subunit, increases the loss of
      receptor responsiveness after the application of acetylcholine (ACh), nicotine,
      or 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXB), an alpha7-selective partial
      agonist. Inhibition of receptor responsiveness following agonist exposure may
      occur through either an enhancement of desensitization, increased channel block
      by an agonist, or alternatively via allosteric modulation. Although DMXB produces
      very little activation of either alpha3beta4 or alpha3beta4(6'F10'T) receptors,
      DMXB shows an enhanced use-and voltage-dependent inhibition of
      alpha3beta4(6'F10'T) receptors compared with wild-type. In contrast, the
      alpha4beta2-selective agonist (E)-N-methyl-4-(3-pyridinyl)-3-butene-1-amine (TC
      2403, previously identified as RJR-2403) shows increased activation of
      alpha3beta4(6'F10'T) receptors compared with alpha3beta4 receptors (as related to
      ACh activation) but with no significant increase in antagonist activity. The
      interaction between the binding of local anesthetics and the functional
      inhibition produced by these agonists was evaluated. The binding of the local
      anesthetics to their inhibitory sites does not affect inhibitory effects of DMXB
      and nicotine. However, TC-2403 can protect receptor function from the inhibitory
      effects of other agonists, suggesting that TC-2403, as well as agonists that
      cause inhibition, may be binding to an allosteric site, either promoting or
      inhibiting channel opening. The ability of TC-2403 to protect receptor function
      from agonist-induced inhibition may point toward valuable new combination drug
      therapies.

PMID- 11961084
TI  - Modulation of cellular expression of glucocorticoid receptor and glucocorticoid
      response element-DNA binding in rat brain during alcohol drinking and withdrawal.
AB  - To define the molecular mechanisms of abnormal hypothalamic pituitary adrenal
      (HPA) axis during ethanol dependence, we investigated the effect of chronic
      ethanol treatment (15 days) and its withdrawal (24 h) on the expression of
      glucocorticoid receptors (GRs) and glucocorticoid response element (GRE)-DNA
      binding in the rat brain. The effects of chronic mianserin [serotonin (5
      HT)(2A/2C) antagonist] treatment on these parameters in various brain structures
      of control diet-fed and ethanol-fed rats were also investigated. It was found
      that ethanol treatment and withdrawal significantly decreased the GR protein
      levels in cortical (cingulate gyrus, frontal, parietal, and piriform cortex) and
      amygdaloid (central, medial, and basolateral) structures and paraventricular
      nucleus (PVN) of hypothalamus of rats. It was also observed that ethanol
      treatment produced significant reductions in GR protein levels in various
      hippocampal structures (CA1, CA2, CA3, and dentate gyrus), but these changes were
      normalized during ethanol withdrawal. Ethanol treatment also significantly
      decreased GRE-DNA binding in rat cortex and hippocampus, which remained decreased
      in the cortex but reverted to normal in hippocampus during ethanol withdrawal.
      Chronic mianserin (alone) treatment had no effect on cortical GRE-DNA binding and
      GR protein levels in cortical, amygdaloid, or PVN structures but significantly
      decreased the GR protein expression in various hippocampal structures and GRE-DNA
      binding in whole hippocampus. However, when administered concurrently with
      ethanol treatment, mianserin significantly antagonized the reductions in cortical
      GRE-DNA binding and in GR protein expression in cortical, PVN, and central, but
      not medial and basolateral, amygdaloid structures during ethanol withdrawal. On
      the other hand, mianserin treatment along with ethanol administration
      significantly decreased the hippocampal GRE-DNA binding and GR protein expression
      in various hippocampal structures during ethanol withdrawal. Furthermore, ethanol
      treatment and its withdrawal or mianserin treatment had no effect on the neuron
      specific nuclear protein levels in the various brain structures. Taken together,
      these results indicate that interaction of 5-HT(2A/2C) receptors with GRs in
      cortical, central amygdaloid, and PVN structures may play a role in neural
      mechanisms of alcohol dependence. It is possible that decreased GR expression in
      PVN may be responsible for the abnormal HPA axis during ethanol exposure and
      withdrawal.

PMID- 11961087
TI  - Enhanced tenodesis for retrocalcaneal surgery.
AB  - Retrocalcaneal surgery is complex and difficult. Over the years, many different
      approaches to retrocalcaneal surgery have been described. Partial or total
      release of the tendo Achillis is often necessary, with reattachment being of
      paramount importance to allow for optimal function following surgery. Although
      numerous anchoring devices have been introduced for tendo Achillis reattachment,
      the authors have found the DePuy TiMAX Spider Plate (DePuy ACE, Warsaw, Indiana)
      to be superior. This article describes the Spider Plate and associated surgical
      technique, which have greatly enhanced the outcome of retrocalcaneal surgery.

PMID- 11961086
TI  - Predislocation syndrome. Progressive subluxation/dislocation of the lesser
      metatarsophalangeal joint.
AB  - Progressive subluxation/dislocation of the lesser toes resulting from idiopathic
      inflammation about one or more of the lesser metatarsophalangeal joints is a
      common cause of metatarsalgia that is frequently unrecognized or misdiagnosed.
      The disorder results from a failure of the plantar plate and collateral ligaments
      that stabilize the metatarsophalangeal joints and is typically associated with
      abnormal forefoot loading patterns. The authors refer to this condition as
      predislocation syndrome and have devised a clinical staging system that is based
      on the clinical signs and symptoms present during examination. A thorough review
      of predislocation syndrome and an overview of the conservative and surgical
      treatment options available for this disorder are presented.

PMID- 11961088
TI  - Evaluation and treatment of stage 0 Charcot's neuroarthropathy of the foot and
      ankle.
AB  - Charcot's neuroarthropathy is a relatively common disease in patients with
      diabetic neuropathy. If unrecognized or left untreated, Charcot's
      neuroarthropathy can result in a severely misshapen and unstable foot and ankle.
      Ulceration, soft-tissue infection, and osteomyelitis frequently ensue, and
      partial or complete amputation of the foot is not uncommon. A high index of
      suspicion and proper interpretation of clinical and diagnostic findings are
      essential to establish a timely and accurate diagnosis and to institute
      appropriate treatment. The pathogenesis of neuroarthropathy is reviewed and
      diagnosis and treatment of the stage 0 diabetic Charcot foot are presented.

PMID- 11961089
TI  - The Jones compression bandage. Review and clinical applications.
AB  - Lower-extremity edema is a common condition that can be caused by many
      pathophysiologic processes. Control of edema associated with surgery or trauma is
      important and will help minimize pain and discomfort and prevent wound
      complications and blisters. Many techniques are used to control edema. The Jones
      compression dressing is an excellent tool that has been used successfully by the
      senior author for 18 years. It continues to be a primary treatment technique for
      the control of edema.

PMID- 11961090
TI  - Syme's amputation. Surgical technique, prosthetic considerations, and case
      reports.
AB  - Amputation at the level of the ankle joint is a valuable but underused procedure
      for a variety of conditions affecting the foot and ankle. The procedure provides
      a comfortable and durable stump that allows the lower-extremity amputee to
      function with minimal disability. This article reviews the indications for Syme's
      amputation, provides a detailed surgical description of the procedure, and
      discusses postoperative prosthetic considerations. In addition, three case
      reports are presented in which Syme's procedure was successfully used as an
      alternative to higher-level amputation.

PMID- 11961091
TI  - Synovial osteochondromatosis. A case report and review of the literature.
AB  - Synovial osteochondromatosis is a benign disease of unknown etiology that
      involves the articular and periarticular structures. The disorder primarily
      affects men, and trauma is the most common predisposing factor. The authors
      review the literature, clinical findings, proposed etiology, classification,
      ancillary tests, histopathology, differential diagnosis, treatment options, and
      prognosis. A case report of this rare entity is also presented.

PMID- 11961092
TI  - Presidential address. The American Podiatric Medical Association.

PMID- 11961093
TI  - Evolution of class B floral homeotic proteins: obligate heterodimerization
      originated from homodimerization.
AB  - The class B floral homeotic genes from the higher eudicot model systems
      Arabidopsis and Antirrhinum are involved in specifying the identity of petals and
      stamens during flower development. These genes exist in two different types
      termed DEF- and GLO-like genes. The proteins encoded by the class B genes are
      stable and functional in the cell only as heterodimeric complexes of a DEF- and a
      GLO-like protein. In line with this, heterodimerization is obligate for DNA
      binding in vitro. The genes whose products have to heterodimerize to be stable
      and functional are each other's closest relatives within their genomes. This
      suggests that the respective genes originated by gene duplication, and that
      heterodimerization is of relative recent origin and evolved from
      homodimerization. To test this hypothesis we have investigated the dimerization
      behavior of putative B proteins from phylogenetic informative taxa, employing
      electrophoretic mobility shift assays and the yeast two-hybrid system. We find
      that an ancestral B protein from the gymnosperm Gnetum gnemon binds DNA in a
      sequence-specific manner as a homodimer. Of the two types of B proteins from the
      monocot Lilium regale, the GLO-like protein is still able to homodimerize,
      whereas the DEF-like protein binds to DNA only as a heterodimeric complex with
      the GLO-like protein. These data suggest that heterodimerization evolved in two
      steps after a gene duplication that gave rise to DEF- and GLO-like genes.
      Heterodimerization may have originated after the gymnosperm-angiosperm split
      about 300 MYA but before the monocot-eudicot split 140-200 MYA.
      Heterodimerization may have become obligate for both types of flowering plant B
      proteins in the eudicot lineage after the monocot-eudicot split.

PMID- 11961095
TI  - Comparative genetics and evolution of annexin A13 as the founder gene of
      vertebrate annexins.
AB  - Annexin A13 (ANXA13) is believed to be the original founder gene of the 12-member
      vertebrate annexin A family, and it has acquired an intestine-specific expression
      associated with a highly differentiated intracellular transport function.
      Molecular characterization of this subfamily in a range of vertebrate species was
      undertaken to assess coding region conservation, gene organization, chromosomal
      linkage, and phylogenetic relationships relevant to its progenitor role in the
      structure-function evolution of the annexin gene superfamily. Protein diagnostic
      features peculiar to this subfamily include an alternate isoform containing a KGD
      motif, an elevated basic amino acid content with polyhistidine expansion in the
      5'-translated region, and the conservation of 15% core tetrad residues specific
      to annexin A13 members. The 12 coding exons comprising the 58-kb human ANXA13
      gene were deduced from BAC clone sequencing, whereas internal repetitive elements
      and neighboring genes in chromosome 8q24.12 were identified by contig analysis of
      the draft sequence from the human genome project. A unique exon splicing pattern
      in the annexin A13 gene was corroborated by coanalysis of mouse, rat, zebrafish,
      and pufferfish genomic DNA and determined to be the most distinct of all
      vertebrate annexins. The putative promoter region was identified by phylogenetic
      footprinting of potential binding sites for intestine-specific transcription
      factors. Mouse annexin A13 cDNA was used to map the gene to an orthologous
      linkage group in mouse chromosome 15 (between Sdc2 and Myc by backcross
      analysis), and the zebrafish cDNA permitted its localization to linkage group 24.
      Comparative analysis of annexin A13 from nine species traced this gene's
      speciation history and assessed coding region variation, whereas phylogenetic
      analysis showed it to be the deepest-branching vertebrate annexin, and
      computational analysis estimated the gene age and divergence rate. The unique,
      conserved aspects of annexin A13 primary structure, gene organization, and
      genetic maps identify it as the probable common ancestor of all vertebrate
      annexins, beginning with the sequential duplication to annexins A7 and A11
      approximately 700 MYA, before the emergence of chordates.

PMID- 11961094
TI  - Differential evolutionary dynamics of duplicated paralogous Adh loci in
      allotetraploid cotton (Gossypium).
AB  - Levels and patterns of nucleotide diversity vary widely among lineages. Because
      allopolyploid species contain duplicated (homoeologous) genes, studies of
      nucleotide diversity at homoeologous loci may facilitate insight into the
      evolutionary dynamics of duplicated loci. In this study, we describe patterns of
      sequence diversity from an alcohol dehydrogenase homoeologous locus pair (AdhC)
      in allotetraploid cotton (Gossypium, Malvaceae). These data are compared with
      equivalent information from another homoeologous alcohol dehydrogenase gene pair
      (AdhA, Small, Ryburn, and Wendel 1999. Mol. Biol. Evol. 16:491-501) which has an
      overall slower evolutionary rate than AdhC. As expected from the predicted
      correlation between nucleotide diversity and evolutionary rate, nucleotide
      diversity was higher for AdhC than for AdhA. In addition, nucleotide diversity is
      higher in the D-subgenome of allotetraploid cotton for AdhC, confirming earlier
      observations for AdhA. These observations indicate that for these two pairs of
      Adh loci, the null hypothesis of equivalent evolutionary dynamics for duplicated
      genes in allotetraploid cotton is rejected.

PMID- 11961096
TI  - Ancient lineages of non-LTR retrotransposons in the primitive eukaryote, Giardia
      lamblia.
AB  - Mobile elements that use reverse transcriptase to make new copies of themselves
      are found in all major lineages of eukaryotes. The non-long terminal repeat (non
      LTR) retrotransposons have been suggested to be the oldest of these eukaryotic
      elements. Phylogenetic analysis of non-LTR elements suggests that they have
      predominantly undergone vertical transmission, as opposed to the frequent
      horizontal transmissions found for other mobile elements. One prediction of this
      vertical model of inheritance is that the oldest lineages of eukaryotes should
      exclusively harbor the oldest lineages of non-LTR retrotransposons. Here we
      characterize the non-LTR retrotransposons present in one of the most primitive
      eukaryotes, the diplomonad Giardia lamblia. Two families of elements were
      detected in the WB isolate of G. lamblia currently being used for the genome
      sequencing project. These elements are clearly distinct from all other previously
      described non-LTR lineages. Phylogenetic analysis indicates that these Genie
      elements (for Giardia early non-LTR insertion element) are among the oldest known
      lineages of non-LTR elements consistent with strict vertical descent. Genie
      elements encode a single open reading frame with a carboxyl terminal endonuclease
      domain. Genie 1 is site specific, as seven to eight copies are present in a
      single tandem array of a 771-bp repeat near the telomere of one chromosome. The
      function of this repeat is not known. One additional, highly divergent, element
      within the Genie 1 lineage is not located in this tandem array but is near a
      second telomere. Four different telomere addition sites could be identified
      within or near the Genie elements on each of these chromosomes. The second
      lineage of non-LTR elements, Genie 2, is composed of about 10 degenerate copies.
      Genie 2 elements do not appear to be site specific in their insertion. An unusual
      aspect of Genie 2 is that all copies contain inverted repeats up to 172 bp in
      length.

PMID- 11961097
TI  - Archaeal phylogeny based on ribosomal proteins.
AB  - Until recently, phylogenetic analyses of Archaea have mainly been based on
      ribosomal RNA (rRNA) sequence comparisons, leading to the distinction of the two
      major archaeal phyla: the Euryarchaeota and the Crenarchaeota. Here, thanks to
      the recent sequencing of several archaeal genomes, we have constructed a
      phylogeny based on the fusion of the sequences of the 53 ribosomal proteins
      present in most of the archaeal species. This phylogeny was remarkably congruent
      with the rRNA phylogeny, suggesting that both reflected the actual phylogeny of
      the domain Archaea even if some nodes remained unresolved. In both cases, the
      branches leading to hyperthermophilic species were short, suggesting that the
      evolutionary rate of their genes has been slowed down by structural constraints
      related to environmental adaptation. In addition, to estimate the impact of
      lateral gene transfer (LGT) on our tree reconstruction, we used a new method that
      revealed that 8 genes out of the 53 ribosomal proteins used in our study were
      likely affected by LGT. This strongly suggested that a core of 45 nontransferred
      ribosomal protein genes existed in Archaea that can be tentatively used to infer
      the phylogeny of this domain. Interestingly, the tree obtained using only the
      eight ribosomal proteins likely affected by LGT was not very different from the
      consensus tree, indicating that LGT mainly brought random phylogenetic noise. The
      major difference involves organisms living in similar environments, suggesting
      that LGTs are mainly directed by the physical proximity of the organisms rather
      than by their phylogenetic proximity.

PMID- 11961098
TI  - Loss of urate oxidase activity in hominoids and its evolutionary implications.
AB  - We have determined and compared the promoter, coding, and intronic sequences of
      the urate oxidase (Uox) gene of various primate species. Although we confirm the
      previous observation that the inactivation of the gene in the clade of the human
      and the great apes results from a single CGA to TGA nonsense mutation in exon 2,
      we find that the inactivation in the gibbon lineage results from an independent
      nonsense mutation at a different CGA codon in exon 2 or from either one-base
      deletion in exon 3 or one-base insertion in exon 5, contrary to the previous
      claim that the cause is a 13-bp deletion in exon 2. We also find that compared
      with other organisms, the primate functional Uox gene is exceptional in terms of
      usage of CGA codons which are prone to TGA nonsense mutations. Nevertheless, we
      demonstrate rather strong selective constraint against nonsynonymous sites of the
      functional Uox gene and argue that this observation is consistent with the fact
      that the Uox gene is unique in the genome and evolutionarily conserved not only
      among animals but also among eukaryotes. Another finding that there are a few
      substitutions in the cis-acting element or CAAT-box (or both) of primate
      functional Uox genes may explain the lowered transcriptional activity. We suggest
      that although the inactivation of the hominoid Uox gene was caused by independent
      nonsense or frameshift mutations, the gene has taken a two-step deterioration
      process, first in the promoter and second in the coding region during primate
      evolution. It is also argued that the high concentration of uric acid in the
      blood of humans and nonhuman primates has developed molecular coevolution with
      the xanthine oxidoreductase in purine metabolism. However, it remains to be
      answered whether loss of Uox activity in hominoids is related to protection from
      oxidative damage and the prolonged life span.

PMID- 11961099
TI  - Evolution of the phosphoglycerate mutase processed gene in human and chimpanzee
      revealing the origin of a new primate gene.
AB  - Processed genes are created by retroposition from messenger RNA of expressed
      genes. The estimated amount of processed copies of genes in the human genome is
      10,000-14,000. Some of these might be pseudogenes with the expected pattern for
      nonfunctional sequences, but some others might be an important source of new
      genes. We have studied the evolution of a Phosphoglycerate mutase processed gene
      (PGAM3) described in humans and believed to be a pseudogene. We sequenced PGAM3
      in chimpanzee and macaque and obtained polymorphism data for human coding region.
      We found evidence that PGAM3 likely produces a functional protein, as an example
      of addressing functionality for human processed pseudogenes. First, the open
      reading frame was intact despite many deletions that occurred in the 3'
      untranslated region. Second, it appears that the gene is expressed. Finally,
      interspecies and intraspecies variation for PGAM3 was not consistent with the
      neutral model proposed for pseudogenes, suggesting that a new functional primate
      gene has originated. Amino acid divergence was significantly higher than
      synonymous divergence in PGAM3 lineage, supporting positive selection acting in
      this gene. This role of selection was further supported by the excess of rare
      alleles in a population genetic analysis. PGAM3 is located in a region of very
      low recombination; therefore, it is conceivable that the rapid fixation events in
      this newly arising gene may have contributed to a selective sweep of variation in
      the region.

PMID- 11961100
TI  - Ylli, a non-LTR retrotransposon L1 family in the dimorphic yeast Yarrowia
      lipolytica.
AB  - During the course of a random sequencing project of the genome of the dimorphic
      yeast Yarrowia lipolytica, we have identified sequences that were repeated in the
      genome and that matched the reverse transcriptase (RT) sequence of non-long
      terminal repeat (non-LTR) retrotransposons. Extension of sequencing on each side
      of this zone of homology allowed the definition of an element over 6 kb long. The
      conceptual translation of this sequence revealed two open reading frames (ORFs)
      that displayed several characteristics of non-LTR retrotransposons: a Cys-rich
      motif in the ORF1, an N-terminal endonuclease, a central RT, and a C-terminal
      zinc finger domain in the ORF2. We called this element Ylli (for Y. lipolytica
      LINE). A total of 19 distinct repeats carrying the 3' untranslated region (UTR)
      and all ending with a poly-A tail were detected. Most of them were very short, 17
      being 134 bp long or less. The number of copies of Ylli was estimated to be
      around 100 if these short repeats are 5' truncations. No 5' UTR was clearly
      identified, indicating that entire and therefore active elements might be very
      rare in the Y. lipolytica strain tested. Ylli does not seem to have any insertion
      specificity. Phylogenetic analysis of the RT domain unambiguously placed Ylli
      within the L1 clade. It forms a monophyletic group with the Zorro non-LTR
      retrotransposons discovered in another dimorphic yeast Candida albicans. BLAST
      comparisons showed that ORF2 of Ylli is closely related to that of the slime mold
      Dictyostelium discoideum L1 family, TRE.

PMID- 11961101
TI  - Nucleotide variation of the duplicated amylase genes in Drosophila kikkawai.
AB  - We examined levels and patterns of the nucleotide polymorphism of the Amylase
      genes with a head-to-head duplication in Drosophila kikkawai. The levels of
      variation in D. kikkawai were comparable to those in Drosophila melanogaster.
      Tajima's test, Fu and Li's test, HKA test, and MK test did not show significant
      departure from neutrality. We found an excess of replacement changes in the
      within-locus class, representing polymorphism in one of the duplicated genes,
      compared with the between-locus class, representing polymorphism shared between
      the duplicated genes. Most replacement changes in the within-locus class were
      singletons. These results suggest that most replacement changes are deleterious.
      A contrasting evolutionary pattern, involving concerted evolution in the coding
      regions but differential evolution in the 5'-flanking regions, was observed.
      However, unlike the duplicated Amy genes of D. melanogaster, the coding regions
      of the duplicated genes in D. kikkawai tended to diverge. Using Ohta's model of
      the small multigene family, we found that recombination (interchromosomal equal
      crossing-over) rate was one order higher than gene conversion (unequal crossing
      over) rate, resulting in a considerable but incomplete homogenization of the
      duplicated coding regions. Linkage disequilibria were found in the intron as well
      as within and around the regulatory cis-element sequences of one of the
      duplicated genes (Amy1). The possible causes of these linkage disequilibria were
      discussed.

PMID- 11961102
TI  - Purifying selection and birth-and-death evolution in the histone H4 gene family.
AB  - Histones are small basic proteins encoded by a multigene family and are
      responsible for the nucleosomal organization of chromatin in eukaryotes. Because
      of the high degree of protein sequence conservation, it is generally believed
      that histone genes are subject to concerted evolution. However, purifying
      selection can also generate a high degree of sequence homogeneity. In this study,
      we examined the long-term evolution of histone H4 genes to determine whether
      concerted evolution or purifying selection was the major factor for maintaining
      sequence homogeneity. We analyzed the proportion (p(S)) of synonymous nucleotide
      differences between the H4 genes from 59 species of fungi, plants, animals, and
      protists and found that p(S) is generally very high and often close to the
      saturation level (p(S) ranging from 0.3 to 0.6) even though protein sequences are
      virtually identical for all H4 genes. A small proportion of genes showed a low
      level of p(S) values, but this appeared to be caused by recent gene duplication.
      Our findings suggest that the members of this gene family evolve according to the
      birth-and-death model of evolution under strong purifying selection. Using
      histone-like genes in archaebacteria as outgroups, we also showed that H1, H2A,
      H2B, H3, and H4 histone genes in eukaryotes form separate clusters and that these
      classes of genes diverged nearly at the same time, before the eukaryotic kingdoms
      diverged.

PMID- 11961103
TI  - Testing a covariotide model of DNA substitution.
AB  - The concomitantly variable codons hypothesis of DNA substitution argues that at
      any time only a fraction of the codons in a gene are capable of accepting a
      mutation. However, as mutations are fixed at some positions in a gene, the sites
      that are potentially variable also change because of changed functional
      constraints. This hypothesis has been termed the "covarion" hypothesis or when
      the model is applied to nucleotides, the "covariotide" hypothesis. The covarion
      covariotide model has proven to be remarkably difficult to test. Here I examine a
      covariotide hypothesis for 11 genes using a likelihood ratio test. I show that in
      nine of the genes examined a covariotide model provides a better explanation of
      the data than a model that does not allow constraints to change over time.

PMID- 11961104
TI  - Evaluation of methods for detecting recombination from DNA sequences: empirical
      data.
AB  - The performance of 14 different recombination detection methods was evaluated by
      analyzing several empirical data sets where the presence of recombination has
      been suggested or where recombination is assumed to be absent. In general,
      recombination methods seem to be more powerful with increasing levels of
      divergence, but different methods showed distinct performance. Substitution
      methods using summary statistics gave more accurate inferences than most
      phylogenetic methods. However, definitive conclusions about the presence of
      recombination should not be derived on the basis of a single method. Performance
      patterns observed from the analysis of real data sets coincided very well with
      previous computer simulation results. Previous recombination inferences from some
      of the data sets analyzed here should be reconsidered. In particular,
      recombination in HIV-1 seems to be much more widespread than previously thought.
      This finding might have serious implications on vaccine development and on the
      reliability of previous inferences of HIV-1 evolutionary history and dynamics.

PMID- 11961105
TI  - Functional diversification during evolution of the murine alpha(1)-proteinase
      inhibitor family: role of the hypervariable reactive center loop.
AB  - Alpha(1)-proteinase inhibitor (alpha(1)-PI) is a member of the serpin superfamily
      of serine proteinase inhibitors that are involved in the regulation of a number
      of proteolytic processes. Alpha(1)-PI, like most serpins, functions by covalent
      binding to, and inhibition of, target proteinases. The interaction between
      alpha(1)-PI and its target is directed by the so-called reactive center loop
      (RCL), an approximately 20 residue domain that extends out from the body of the
      alpha(1)-PI polypeptide and determines the inhibitor's specificity. Mice express
      at least seven closely related alpha(1)-PI isoforms, encoded by a family of genes
      clustered at the Spi1 locus on chromosome 12. The amino acid sequence of the RCL
      region is hypervariable among alpha(1)-PIs, a phenomenon that has been attributed
      to high rates of evolution driven by positive Darwinian selection. This suggests
      that the various isoforms are functionally diverse. To test this notion, we have
      compared the proteinase specificities of individual alpha(1)-PIs from each of the
      two mouse species. As predicted from the positive Darwinian selection hypothesis,
      the various alpha(1)-PIs differ in their ability to form covalent complexes with
      serine proteinases, such as elastase, trypsin, chymotrypsin, and cathepsin G. In
      addition, they differ in their binding ability to proteinases in crude snake
      venoms. Importantly, the RCL region of the alpha(1)-PI polypeptide is the primary
      determinant of isoform-specific differences in proteinase recognition, indicating
      that hypervariability within this region drives the functional diversification of
      alpha(1)-PIs during evolution. The possible physiological benefits of alpha(1)-PI
      diversity are discussed.

PMID- 11961106
TI  - Genome evolution and developmental constraint in Caenorhabditis elegans.
AB  - It has been hypothesized that evolutionary changes will be more frequent in later
      ontogeny than early ontogeny because of developmental constraint. To test this
      hypothesis, a genomewide examination of molecular evolution through ontogeny was
      carried out using comparative genomic data in Caenorhabditis elegans and
      Caenorhabditis briggsae. We found that the mean rate of amino acid replacement is
      not significantly different between genes expressed during and after
      embryogenesis. However, synonymous substitution rates differed significantly
      between these two classes. A genomewide survey of correlation between codon bias
      and expression level found codon bias to be significantly correlated with mRNA
      expression (r(s) = -0.30 and P < 10(-131)) but does not alone explain differences
      in dS between classes. Surprisingly, it was found that genes expressed after
      embryogenesis have a significantly greater number of duplicates in both the C.
      elegans and C. briggsae genomes (P < 10(-20) and P < 10(-13)) when compared with
      early-expressed and nonmodulated genes. A similarity in the distribution of
      duplicates of nonmodulated and early-expressed genes, as well as a
      disproportionately higher number of early pseudogenes, lend support to the
      hypothesis that this difference in duplicate number is caused by selection
      against gene duplicates of early-expressed genes, reflecting developmental
      constraint. Developmental constraint at the level of gene duplication may have
      important implications for macroevolutionary change.

PMID- 11961107
TI  - Molecular evolution of nuclear genes in Cupressacea, a group of conifer trees.
AB  - We surveyed the molecular evolutionary characteristics of 11 nuclear genes from
      10 conifer trees belonging to the Taxodioideae, the Cupressoideae, and the
      Sequoioideae. Comparisons of substitution rates among the lineages indicated that
      the synonymous substitution rates of the Cupressoideae lineage were higher than
      those of the Taxodioideae. This result parallels the pattern previously found in
      plastid genes. Likelihood-ratio tests showed that the nonsynonymous-synonymous
      rate ratio did not change significantly among lineages. In addition, after
      adjustments for lineage effects, the dispersion indices of synonymous and
      nonsynonymous substitutions were considerably reduced, and the latter was close
      to 1. These results indicated that the acceleration of evolutionary rates in the
      Cupressoideae lineage occurred in both the nuclear and plastid genomes, and that
      generally, this lineage effect affected synonymous and nonsynonymous
      substitutions similarly. We also investigated the relationship of synonymous
      substitution rates with the nonsynonymous substitution rate, base composition,
      and codon bias in each lineage. Synonymous substitution rates were positively
      correlated with nonsynonymous substitution rates and GC content at third codon
      positions, but synonymous substitution rates were not correlated with codon bias.
      Finally, we tested the possibility of positive selection at the protein level,
      using maximum likelihood models, assuming heterogeneous nonsynonymous-synonymous
      rate ratios among codon (amino acid) sites. Although we did not detect strong
      evidence of positively selected codon sites, the analysis suggested that
      significant variation in nonsynonymous-synonymous rate ratio exists among the
      sites. The most likely sites for action of positive selection were found in the
      ferredoxin gene, which is an important component of the apparatus for
      photosynthesis.

PMID- 11961108
TI  - An insect molecular clock dates the origin of the insects and accords with
      palaeontological and biogeographic landmarks.
AB  - A unified understanding of >390 Myr of insect evolution requires insight into
      their origin. Molecular clocks are widely applied for evolutionary dating, but
      clocks for the class Insecta have remained elusive. We now define a robust
      nucleotide and amino acid mitochondrial molecular clock encompassing five insect
      orders, including the Blattaria (cockroaches), Orthoptera (crickets and locusts),
      Hemiptera (true bugs), Diptera, and Lepidoptera (butterflies and moths).
      Calibration of the clock using one of the earliest, most extensive fossil records
      for insects (the early ancestors of extant Blattaria) was congruent with all
      available insect fossils, with biogeographic history, with the Cambrian
      explosion, and with independent dating estimates from Lepidopteran families. In
      addition, dates obtained from both nucleotide and amino acid clocks were
      congruent with each other. Of particular interest to vector biology is the early
      date of the emergence of triatomine bugs (99.8-93.5 MYA), coincident with the
      formation of the South American continent during the breakup of Gondwanaland.
      More generally, we reveal the insects arising from a common ancestor with the
      Anostraca (fairy shrimps) at around the Silurian-Ordovician boundary (434.2-421.1
      MYA) coinciding with the earliest plant megafossil. We explore Tilyard's theory
      proposing that the terrestrial transition of the aquatic arthropod ancestor to
      the insects is associated with a particular plant group (early vascular plants).
      The major output of the study is a comprehensive series of dates for deep
      branching points within insect evolution that can act as calibration points for
      further dating studies within insect families and genera.

PMID- 11961109
TI  - Evaluating hypotheses of deuterostome phylogeny and chordate evolution with new
      LSU and SSU ribosomal DNA data.
AB  - We investigated evolutionary relationships among deuterostome subgroups by
      obtaining nearly complete large-subunit ribosomal RNA (LSU rRNA)-gene sequences
      for 14 deuterostomes and 3 protostomes and complete small-subunit (SSU) rRNA-gene
      sequences for five of these animals. With the addition of previously published
      sequences, we compared 28 taxa using three different data sets (LSU only, SSU
      only, and combined LSU + SSU) under minimum evolution (with LogDet distances),
      maximum likelihood, and maximum parsimony optimality criteria. Additionally, we
      analyzed the combined LSU + SSU sequences with spectral analysis of LogDet
      distances, a technique that measures the amount of support and conflict within
      the data for every possible grouping of taxa. Overall, we found that (1) the LSU
      genes produced a tree very similar to the SSU gene tree, (2) adding LSU to SSU
      sequences strengthened the bootstrap support for many groups above the SSU-only
      values (e.g., hemichordates plus echinoderms as Ambulacraria; lancelets as the
      sister group to vertebrates), (3) LSU sequences did not support SSU-based
      hypotheses of pterobranchs evolving from enteropneusts and thaliaceans evolving
      from ascidians, and (4) the combined LSU + SSU data are ambiguous about the
      monophyly of chordates. No tree-building algorithm united urochordates
      conclusively with other chordates, although spectral analysis did so, providing
      our only evidence for chordate monophyly. With spectral analysis, we also
      evaluated several major hypotheses of deuterostome phylogeny that were
      constructed from morphological, embryological, and paleontological evidence. Our
      rRNA-gene analysis refutes most of these hypotheses and thus advocates a
      rethinking of chordate and vertebrate origins.

PMID- 11961111
TI  - G protein-coupled receptors as direct targets of inhaled anesthetics.
AB  - The molecular pharmacology of inhalational anesthetics remains poorly understood.
      Despite accumulating evidence suggesting that neuronal membrane proteins are
      potential targets of inhaled anesthetics, most currently favored membrane protein
      targets lack any direct evidence for anesthetic binding. We report herein the
      location of the binding site for the inhaled anesthetic halothane at the amino
      acid residue level of resolution in the ligand binding cavity in a prototypical G
      protein-coupled receptor, bovine rhodopsin. Tryptophan fluorescence quenching and
      direct photoaffinity labeling with [(14)C]halothane suggested an interhelical
      location of halothane with a stoichiometry of 1 (halothane/rhodopsin molar
      ratio). Radiosequence analysis of [(14)C]halothane-labeled rhodopsin revealed
      that halothane contacts an amino acid residue (Trp265) lining the ligand binding
      cavity in the transmembrane core of the receptor. The predicted functional
      consequence, competition between halothane and the ligand retinal, was shown here
      by spectroscopy and is known to exist in vivo. These data suggest that
      competition with endogenous ligands may be a general mechanism of the action of
      halothane at this large family of signaling proteins.

PMID- 11961110
TI  - Retortamonad flagellates are closely related to diplomonads--implications for the
      history of mitochondrial function in eukaryote evolution.
AB  - We present the first molecular phylogenetic examination of the evolutionary
      position of retortamonads, a group of mitochondrion-lacking flagellates usually
      found as commensals of the intestinal tracts of vertebrates. Our phylogenies
      include small subunit ribosomal gene sequences from six retortamonad isolates
      four from mammals and two from amphibians. All six sequences were highly similar
      (95%-99%), with those from mammals being almost identical to each other. All
      phylogenetic methods utilized unequivocally placed retortamonads with another
      amitochondriate group, the diplomonads. Surprisingly, all methods weakly
      supported a position for retortamonads cladistically within diplomonads, as the
      sister group to Giardia. This position would conflict with a single origin and
      uniform retention of the doubled-cell organization displayed by most diplomonads,
      but not by retortamonads. Diplomonad monophyly was not rejected by Shimodaira
      Hasegawa, Kishino-Hasegawa, and expected likelihood weights methods but was
      marginally rejected by parametric bootstrapping. Analyses with additional
      phylogenetic markers are needed to test this controversial branching order within
      the retortamonad + diplomonad clade. Nevertheless, the robust phylogenetic
      association between diplomonads and retortamonads suggests that they share an
      amitochondriate ancestor. Because strong evidence indicates that diplomonads have
      secondarily lost their mitochondria (rather than being ancestrally
      amitochondriate), our results imply that retortamonads are also secondarily
      amitochondriate. Of the various groups of eukaryotes originally suggested to be
      primitively amitochondriate under the archezoa hypothesis, all have now been
      found to have physical or genetic mitochondrial relics (or both) or form a robust
      clade with an organism with such a relic.

PMID- 11961112
TI  - Parthenolide, an inhibitor of the nuclear factor-kappaB pathway, ameliorates
      cardiovascular derangement and outcome in endotoxic shock in rodents.
AB  - Parthenolide is a sesquiterpene lactone used in folk medicine for its anti
      inflammatory activity. Recent in vitro studies have shown that this compound
      inhibits the nuclear factor (NF)-kappaB pathway. This study examines the effect
      of parthenolide in endotoxic shock in rodents. Endotoxic shock was induced by
      administration of Escherichia coli endotoxin in rats. Three groups of rats
      received parthenolide (0.25, 0.5, or 1 mg/kg) 15 min before endotoxin; another
      group received parthenolide (1 mg/kg) 3 h after endotoxin. In vehicle-treated
      rats, administration of endotoxin caused severe hypotension, which was associated
      with a marked hyporeactivity to norepinephrine in ex vivo thoracic aortas.
      Immunohistochemistry showed positive staining for nitrotyrosine, poly(ADP-ribose)
      synthetase (PARS) and apoptosis, whereas Northern blot analysis showed increased
      mRNA expression of inducible nitric-oxide synthase (iNOS) in thoracic aortas.
      Elevated levels of plasma nitrate/nitrite were also found. Elevated lung levels
      of myeloperoxidase activity were indicative of infiltration of neutrophils. These
      inflammatory events were preceded by cytosolic degradation of inhibitor
      kappaBalpha (IkappaBalpha) and activation of nuclear NF-kappaB in the lung. In
      vivo pretreatment and post-treatment with parthenolide improved the hemodynamic
      profile and reduced plasma nitrate/nitrite and lung neutrophil infiltration in a
      dose-dependent fashion. Vascular hyporeactivity of ex vivo aortas was
      ameliorated. Treatment with parthenolide also abolished nitrotyrosine formation,
      PARS expression, and apoptosis and reduced iNOS mRNA content in thoracic aortas.
      DNA binding of NF-kappaB was inhibited by parthenolide in the lung, whereas
      degradation of IkappaBalpha was unchanged. In a separate set of experiments,
      pretreatment or post-treatment with parthenolide significantly improved survival
      in mice challenged with endotoxin. We conclude that parthenolide exerts
      beneficial effects during endotoxic shock through inhibition of NF-kappaB.

PMID- 11961113
TI  - Three-dimensional quantitative structure-activity relationships of inhibitors of
      P-glycoprotein.
AB  - P-glycoprotein (P-gp) is an efflux transporter involved in limiting the oral
      bioavailability and tissue penetration of a variety of structurally divergent
      molecules. A better understanding of the structural requirements of modulators of
      P-gp function will aid in the design of therapeutic agents. Toward this goal,
      three-dimensional quantitative structure-activity relationship (3D-QSAR) models
      were generated using in vitro data associated with inhibition of P-gp function.
      Several approaches were undertaken with multiple iterations, yielding Catalyst 3D
      QSAR models being able to qualitatively rank-order and predict IC(50) values for
      P-gp inhibitors excluded from the model in question. The success of these
      validations suggests that a P-gp pharmacophore for 27 inhibitors of digoxin
      transport in Caco-2 cells consisted of four hydrophobes and one hydrogen bond
      acceptor. A second pharmacophore generated with 21 inhibitors of vinblastine
      binding to plasma membrane vesicles derived from CEM/VLB(100) cells contained
      three ring aromatic features and one hydrophobic feature. A third pharmacophore
      generated with 17 inhibitors of vinblastine accumulation in P-gp expressing LLC
      PK1 cells contained four hydrophobes and one hydrogen bond acceptor. A final
      pharmacophore was generated for inhibition of calcein accumulation in P-gp
      expressing LLC-PK1 cells and found to contain two hydrophobes, a ring aromatic
      feature, and a hydrogen bond donor. The similarity of features for the
      pharmacophores of P-gp inhibitors of digoxin transport and vinblastine binding
      suggest some commonality in their binding sites. Utilization of such models may
      prove to be of value for prediction of molecules that may modulate one or more P
      gp binding sites.

PMID- 11961114
TI  - Application of three-dimensional quantitative structure-activity relationships of
      P-glycoprotein inhibitors and substrates.
AB  - Using in vitro data, we previously built Catalyst 3-dimensional quantitative
      structure activity relationship (3D-QSAR) models that qualitatively rank and
      predict IC(50) values for P-glycoprotein (P-gp) inhibitors. These models were
      derived and tested with data for inhibition of digoxin transport, calcein
      accumulation, vinblastine accumulation, and vinblastine binding. In the present
      study, 16 inhibitors of verapamil binding to P-gp were predicted using these
      models. These inhibition results were then used to generate a new pharmacophore
      that consisted of one hydrogen bond acceptor, one ring aromatic feature, and two
      hydrophobes. This model predicted the rank order of the four data sets described
      previously and correctly ranked the inhibitory potency of a further four
      verapamil metabolites identified in the literature. The degree of similarity in
      rank ordering prediction by these inhibitor pharmacophore models generated to
      date confirms a likely overlap in the sites to which the three P-gp substrates
      used in these studies (verapamil, vinblastine, and digoxin) bind. Alignment of
      the three substrate probes indicated that they are likely to bind the same or
      overlapping sites within P-gp. Important features on these substrates include
      multiple hydrophobic and hydrogen bond acceptor features, which are widely
      dispersed and in agreement among most of the five inhibitor pharmacophores we
      have described so far. These 3D-QSAR models will be useful for future prediction
      of likely substrates and inhibitors of P-gp.

PMID- 11961115
TI  - Expression and functional characterization of rat organic anion transporter 3
      (rOat3) in the choroid plexus.
AB  - We reported previously that an efficient efflux system for benzylpenicillin (PCG)
      is located on the choroid plexus (CP). In this study, we investigated the
      involvement of rat organic anion transporter 1 (rOat1; Slc22a6) and rOat3
      (Slc22a8) in the uptake of PCG and p-aminohippurate (PAH) by the CP. Western blot
      analysis indicates the expression of rOat3, but not rOat1, on the CP, and
      immunohistochemical staining shows that rOat3 is localized on the brush border
      membrane of the choroid epithelial cells. PCG and PAH were found to be taken up
      by isolated rat CP, with K(m) values of 111 and 354 microM, respectively. A
      mutual inhibition study suggests that the same transporter is responsible for the
      uptake of PCG and PAH by isolated rat CP. This was confirmed by examining the
      effect of organic anions and cimetidine on their uptake. Estradiol-17beta
      glucuronide and cimetidine were found to be selective inhibitors of rOat3. The
      inhibition constants of the inhibitors including estradiol-17beta-glucuronide and
      cimetidine were comparable for the uptake of PAH and PCG by isolated rat CP. In
      addition, these values were also comparable with those for rOat3, but not with
      those for rOat1. These results suggest that rOat3 is mainly responsible for the
      uptake of PCG and PAH by isolated rat CP, and it functions as one of the
      detoxification systems on the CP by removing its substrates from the
      cerebrospinal fluid.

PMID- 11961116
TI  - L-Acetylcarnitine induces analgesia by selectively up-regulating mGlu2
      metabotropic glutamate receptors.
AB  - L-Acetylcarnitine (LAC, 100 mg/kg, s.c.), a drug commonly used for the treatment
      of painful neuropathies, substantially reduced mechanical allodynia in rats
      subjected to monolateral chronic constriction injury (CCI) of the sciatic nerve
      and also attenuated acute thermal pain in intact rats. In both cases, induction
      of analgesia required repeated injections of LAC, suggesting that the drug
      induces plastic changes within the nociceptive pathway. In both CCI- and sham
      operated rats, a 24-day treatment with LAC increased the expression of
      metabotropic glutamate (mGlu) receptors 2 and 3 in the lumbar segment of the
      spinal cord, without changing the expression of mGlu1a or -5 receptors. A similar
      up-regulation of mGlu2/3 receptors was detected in the dorsal horns and dorsal
      root ganglia of intact rats treated with LAC for 5-7 days, a time sufficient for
      the induction of thermal analgesia. Immunohistochemical analysis showed that LAC
      treatment enhanced mGlu2/3 immunoreactivity in the inner part of lamina II and in
      laminae III and IV of the spinal cord. An increased mGlu2/3 receptor expression
      was also observed in the cerebral cortex but not in the hippocampus or cerebellum
      of LAC-treated animals. Reverse transcription-polymerase chain reaction combined
      with Northern blot analysis showed that repeated LAC injections selectively
      induced mGlu2 mRNA in the dorsal horns and cerebral cortex (but not in the
      hippocampus). mGlu3 mRNA levels did not change in any brain region of LAC-treated
      animals. To examine whether the selective up-regulation of mGlu2 receptors had
      any role in LAC-induced analgesia, we have used the novel compound LY 341495,
      which is a potent and systemically active mGlu2/3 receptor antagonist. LAC
      induced analgesia was largely reduced 45 to 75 min after a single injection of LY
      341495 (1 mg/kg, i.p.) in both CCI rats tested for mechanical allodynia and
      intact rats tested for thermal pain. We conclude that LAC produces analgesia
      against chronic pain produced not only by peripheral nerve injury but also by
      acute pain in intact animals and that LAC-induced analgesia is associated with
      and causally related to a selective up-regulation of mGlu2 receptors. This offers
      the first example of a selective induction of mGlu2 receptors and discloses a
      novel mechanism for drug-induced analgesia.

PMID- 11961117
TI  - The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2)
      attenuates the development of acute and chronic inflammation.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily of ligand-activated transcription factors that are
      related to retinoid, steroid, and thyroid hormone receptors. The PPAR-gamma
      receptor subtype seems to play a pivotal role in the regulation of cellular
      proliferation and inflammation. Recent evidence also suggests that the
      cyclopentenone prostaglandin (PG) 15-deoxyDelta(12,14)-PGJ(2) (15d-PGJ(2)), which
      is a metabolite of prostaglandin D(2), functions as an endogenous ligand for PPAR
      gamma. We postulated that 15d-PGJ(2) would attenuate inflammation. In the present
      study, we have investigated the effects of 15d-PGJ(2) of acute and chronic
      inflammation (carrageenan-induced pleurisy and collagen-induced arthritis,
      respectively) in animal models. We report for the first time, to our knowledge,
      that 15d-PGJ(2) (given at 10, 30, or 100 microg/kg i.p. in the pleurisy model or
      at 30 microg/kg i.p every 48 h in the arthritis model) exerts potent anti
      inflammatory effects (e.g., inhibition of pleural exudate formation, mononuclear
      cell infiltration, delayed development of clinical indicators, and histological
      injury) in vivo. Furthermore, 15d-PGJ(2) reduced the increase in the staining
      (immunohistochemistry) for nitrotyrosine and poly (ADP-ribose) polymerase and the
      expression of inducible nitric-oxide synthase and cyclooxygenase-2 in the lungs
      of carrageenan-treated mice and in the joints from collagen-treated mice. Thus,
      15d-PGJ(2) reduces the development of acute and chronic inflammation. Therefore,
      the cyclopentenone prostaglandin 15d-PGJ(2) may be useful in the therapy of acute
      and chronic inflammation.

PMID- 11961119
TI  - Antidepressant treatments induce the expression of basic fibroblast growth factor
      in cortical and hippocampal neurons.
AB  - New experimental evidence suggests that the mechanism of action of
      antidepressants includes the induction of neurotrophic factor synthesis in
      selected brain areas. The present study is aimed at establishing whether
      prolonged antidepressant treatments increase the expression of basic fibroblast
      growth factor (FGF2), a polypeptide growth factor that has a broad neurotrophic
      activity in the adult central nervous system. Rats received a single dose or long
      term (3 weeks) administration of desipramine (DMI), fluoxetine (FLU), and
      mianserin (MIA), then were sacrificed at 5 and 24 h after the last injection.
      RNase protection assay and Western blot analysis revealed that all antidepressant
      drugs elicited an anatomically specific increase in FGF2 mRNA and protein. The
      increase in FGF2 mRNA after a single injection was seen only at 5 h after the
      injection and was restricted to the entorhinal cortex, whereas the effect of the
      long-term treatments lasted up to 24 h and occurred in the entire cortex and
      hippocampus. Immunohistochemical analysis of FGF2 immunoreactivity was carried
      out to investigate which cell types responded to the antidepressant treatments.
      DMI and MIA increased FGF2 proteins predominantly in neurons of layer V
      throughout the cerebral cortex and in some neurofilament-positive cells of the
      hippocampus. FLU increased FGF2 immunoreactivity mainly in neurofilament-positive
      cells of the hippocampus. These findings may explain the therapeutic efficacy of
      antidepressants in affective disorders.

PMID- 11961118
TI  - Differences in the cellular localization and agonist-mediated internalization
      properties of the alpha(1)-adrenoceptor subtypes.
AB  - The cellular localization, agonist-mediated internalization, and desensitization
      properties of the alpha(1)-adrenoceptor (alpha(1)-AR) subtypes conjugated with
      green fluorescent protein (alpha(1)-AR/GFP) were assessed using real-time imaging
      of living, transiently transfected human embryonic kidney (HEK) 293 cells. The
      alpha(1B)-AR/GFP fluorescence was detected predominantly on the cell surface.
      Stimulation of the alpha(1B)-AR with phenylephrine led to an increase in
      extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and promoted
      rapid alpha(1B)-AR/GFP internalization. Long-term exposure (15 h) to
      phenylephrine resulted in desensitization of the alpha(1B)-AR-mediated activation
      of ERK1/2 phosphorylation. Alpha(1A)-AR/GFP fluorescence was detected not only on
      the cell surface but also intracellularly. The rate of internalization of the
      cell surface population alpha(1A)-AR/GFPs was slower than that seen for the
      alpha(1B)-AR. Agonist exposure also resulted in desensitization of the alpha(1A)
      AR-mediated increase in ERK1/2 phosphorylation. The alpha(1D)-AR/GFP fluorescence
      was detected mainly intracellularly, and this localization was unaffected by
      exposure to phenylephrine. Phenylephrine treatment of alpha(1D)-AR/GFP expressing
      cells increased ERK1/2 phosphorylation. However, this increase was not
      significant. Cotransfection with beta-arrestin 1 did not increase the rate or
      extent of agonist-stimulated alpha(1A)- or alpha(1B)-AR/GFP internalization.
      However, a dominant-negative form of the beta-arrestin 1, beta-arrestin 1 (319
      418), blocked agonist-mediated internalization of both the alpha(1A)- and
      alpha(1B)-ARs. These data show that transfected alpha(1)-AR/GFP fusion proteins
      are functional, that there are differences in the cellular distribution and
      agonist-mediated internalization between the alpha(1)-ARs, and that agonist
      mediated alpha(1)-AR internalization is dependent on arrestins and can be
      desensitized by long-term exposure to an agonist. These differences could
      contribute to the diversity in physiologic responses regulated by the alpha(1)
      ARs.

PMID- 11961120
TI  - Mutagenesis and modelling of the alpha(1b)-adrenergic receptor highlight the role
      of the helix 3/helix 6 interface in receptor activation.
AB  - Computer simulations on a new model of the alpha1b-adrenergic receptor based on
      the crystal structure of rhodopsin have been combined with experimental
      mutagenesis to investigate the role of residues in the cytosolic half of helix 6
      in receptor activation. Our results support the hypothesis that a salt bridge
      between the highly conserved arginine (R143(3.50)) of the E/DRY motif of helix 3
      and a conserved glutamate (E289(6.30)) on helix 6 constrains the alpha1b-AR in
      the inactive state. In fact, mutations of E289(6.30) that weakened the R143(3.50)
      E289(6.30) interaction constitutively activated the receptor. The functional
      effect of mutating other amino acids on helix 6 (F286(6.27), A292(6.33),
      L296(6.37), V299(6.40,) V300(6.41), and F303(6.44)) correlates with the extent of
      their interaction with helix 3 and in particular with R143(3.50) of the E/DRY
      sequence.

PMID- 11961121
TI  - Reduced phosphodiesterase 3 activity and phosphodiesterase 3A level in synthetic
      vascular smooth muscle cells: implications for use of phosphodiesterase 3
      inhibitors in cardiovascular tissues.
AB  - Vascular smooth muscle cells (VSMC) in situ function to control contraction and
      are said to express a contractile phenotype. However, during development or in
      response to vascular damage, VSMC proliferate and express a more synthetic
      phenotype. A survey of literature values for contractile and synthetic VSMC
      phosphodiesterase (PDE) 3 and PDE4 activities identified a marked difference in
      the PDE3 and PDE4 activities of these cells. In this study, a comparison of PDE3
      and PDE4 activities in contractile and synthetic VSMC demonstrates that a reduced
      PDE3/PDE4 activity ratio in synthetic VSMC correlates with a reduced PDE3
      activity and is associated with marked reductions in PDE3A mRNA and protein
      levels. Because we show that similar reductions in PDE3 activity and PDE3A levels
      occur upon culture of human aortic VSMC and that this phenomenon associates with
      the phenotypic switch that occurs to VSMC in response to vascular damage, our
      findings are presented in the context that PDE3 inhibition might be expected to
      selectively alter functions of contractile VSMC.

PMID- 11961122
TI  - Refinement of the conformation of a critical region of charge-charge interaction
      between cholecystokinin and its receptor.
AB  - Insight into the molecular basis of cholecystokinin (CCK) binding to its receptor
      has come from receptor mutagenesis and photoaffinity labeling studies, with both
      contributing to the current hypothesis that the acidic Tyr-sulfate-27 residue
      within the peptide is situated adjacent to basic Arg(197) in the second loop of
      the receptor. Here, we refine our understanding of this region of interaction by
      examining a structure-activity series of these positions within both ligand and
      receptor and by performing three-dimensional molecular modeling of key pairs of
      modified ligand and receptor constructs. The important roles of Arg(197) and Tyr
      sulfate-27 were supported by the marked negative impact on binding and biological
      response with their natural partner molecule when the receptor residue was
      replaced by acidic Asp or Glu and when the peptide residue was replaced by basic
      Arg, Lys, p-amino-Phe, p-guanidino-Phe, or p-methylamino-Phe. Complementary
      ligand-receptor charge-exchange experiments were unable to regain the lost
      function. This was supported by the molecular modeling, which demonstrated that
      the charge-reversed double mutants could not form a good interaction without
      extensive rearrangement of receptor conformation. The models further predicted
      that R197D and R197E mutations would lead to conformational changes in the
      extracellular domain, and this was experimentally supported by data showing that
      these mutations decreased peptide agonist and antagonist binding and increased
      nonpeptidyl antagonist binding. These receptor constructs also had increased
      susceptibility to trypsin degradation relative to the wild-type receptor. In
      contrast, the relatively conservative R197K mutation had modest negative impact
      on peptide agonist binding, again consistent with the modeling demonstration of
      loss of a series of stabilizing inter- and intramolecular bonds. The strong
      correlation between predicted and experimental results support the reported
      refinement in the three-dimensional structure of the CCK-occupied receptor.

PMID- 11961123
TI  - 2-Methoxyestradiol and analogs as novel antiproliferative agents: analysis of
      three-dimensional quantitative structure-activity relationships for DNA synthesis
      inhibition and estrogen receptor binding.
AB  - 2-Methoxyestradiol (2-MEO), a metabolite of estrogen, is an attractive lead
      compound for the development of novel antitumor and anti-inflammatory agents,
      because it embodies antiproliferative and antiangiogenic activities in one
      molecule. However, the affinity of 2-MEO for the estrogen receptor would lead to
      undesirable side effects. As a prelude to the design of 2-MEO-like compounds with
      an optimal activity profile, we assayed 2-MEO and a series of analogs for their
      ability to cause G(1) cell-cycle arrest (by measuring inhibition of DNA synthesis
      in human cultured airway smooth muscle) and to inhibit binding of [(3)H]estradiol
      at the estrogen receptor (ER; from rat uterine smooth muscle). One compound, a
      diacetoxy enediol derivative, was identified with reasonable potency for DNA
      synthesis (pIC(50) = 5.97) but showed negligible affinity for the ER (pIC(50) <
      5). Three-dimensional quantitative structure-activity relationships were
      developed for these activities using comparative molecular field analysis (CoMFA)
      techniques. Comparison of optimized CoMFA models revealed distinct structural
      requirements for DNA synthesis inhibition and ER binding. For example, DNA
      synthesis inhibition is enhanced by electropositive substitutions in the 2
      position below the plane of the steroid A-ring, whereas ER binding is favored by
      electronegative substitution in this position. Similarly, DNA synthesis
      inhibition correlates negatively with increased steric bulk in regions clustered
      around the A and B rings; changes in steric bulk in these regions has little
      correlation with ER binding. These observations will guide the design of new
      analogs with improved potency for desired characteristics (e.g., DNA synthesis
      inhibition) with minimal unwanted activities (e.g., ER binding).

PMID- 11961124
TI  - Importance of the gamma-aminobutyric acid(B) receptor C-termini for G-protein
      coupling.
AB  - Functional gamma-aminobutyric acid(B) (GABA(B)) receptors assemble from two
      subunits, GABA(B(1)) and GABA(B(2).) This heteromerization, which involves a C
      terminal coiled-coil interaction, ensures efficient surface trafficking and
      agonist-dependent G-protein activation. In the present study, we took a closer
      look at the implications of the intracellular C termini of GABA(B(1)) and
      GABA(B(2)) for G-protein coupling. We generated a series of C-terminal mutants of
      GABA(B(1)) and GABA(B(2)) and tested them for physical interaction, surface
      trafficking, coupling to adenylyl cyclase, and G-protein-gated inwardly
      rectifying potassium channels in human embryonic kidney (HEK) 293 cells as well
      as on endogenous calcium channels in sympathetic neurons of the superior cervical
      ganglion (SCG). We found that the C-terminal interaction contributes only partly
      to the heterodimeric assembly of the subunits, indicating the presence of an
      additional interaction site. The described endoplasmic reticulum retention signal
      within the C terminus of GABA(B(1)) functioned only in the context of specific
      amino acids, which constitute part of the GABA(B(1)) coiled-coil sequence. This
      finding may provide a link between the retention signal and its shielding by the
      coiled coil of GABA(B(2).) In HEK293 cells, we observed that the two well-known
      GABA(B) receptor antagonists [S-(R*,R*)]-[3-[[1-(3,4-dichlorophenyl)ethyl]amino]
      2-hydroxypropyl](cyclohexylmethyl) phosphinic acid (CGP54626) and (+)-(2S)-5,5
      dimethyl-2-morpholineacetic acid (SCH50911) CGP54626 and SCH50911 function as
      inverse agonists. The C termini of GABA(B(1)) and GABA(B(2)) strongly influenced
      agonist-independent G-protein coupling, although they were not necessary for
      agonist-dependent G-protein coupling. The C-terminal GABA(B) receptor mutants
      described here demonstrate that the active receptor conformation is stabilized by
      the coiled-coil interaction. Thus, the C-terminal conformation of the GABA(B)
      receptor may determine its constitutive activity, which could be a therapeutic
      target for inverse agonists.

PMID- 11961125
TI  - Functional and analytical evidence for scavenging of oxygen radicals by L
      arginine.
AB  - L-Arginine, the substrate of nitric oxide synthase, is known to exert favorable
      effects in the prevention and treatment of cardiovascular diseases. In several
      conditions, including atherosclerosis and ischemia/reperfusion, where oxygen
      metabolites are thought to mediate endothelial and myocardial injury, L-arginine
      has protective effects. Here we studied the mechanisms by which L-arginine
      protects against oxygen radical-induced myocardial injury. Buffer-perfused rat
      hearts were subjected to oxygen radicals generated by electrolysis or to
      hypoxanthine and xanthine oxidase, which generates superoxide anions (O(2)). Both
      sources of radicals impaired myocardial contractility, whereas L-arginine
      prevented the impairment. The observation that D-arginine as well as nitric oxide
      synthase inhibitors, such as N(G)-nitro-L-arginine but not glycine, had similar
      cardioprotective effects indicated that the protection might be due to a direct
      chemical interaction of L-arginine and its derivatives with oxygen radicals. In
      support, L-arginine and the derivatives prevented the formation of O(2) as
      determined by sensitive standard methods, whereas glycine did not. The radical
      scavenging activity of L-arginine and derivatives was dose-dependent, with an
      apparent rate constant of approximately 4.8 x 10(3) M s(-1) for the reaction of L
      arginine with O(2) as determined by electron paramagnetic resonance spectroscopy
      using 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine (TEMPONE-H) as spin trap. In
      summary, the results of this study demonstrate protective effects of L-arginine
      against oxygen radical-induced cardiac injury by free radical scavenging.

PMID- 11961126
TI  - Post-transcriptional regulation of hepatic NADPH-cytochrome P450 reductase by
      thyroid hormone: independent effects on poly(A) tail length and mRNA stability.
AB  - Thyroid hormone [triiodothyronine (T3)] positively regulates NADPH cytochrome
      P450 reductase (P450R) mRNA expression in rat liver, with P450R transcription
      initiation being a key regulated step. T3 is presently shown to have significant
      post-transcriptional effects on P450R expression. T3 increased the size of
      cytoplasmic P450R mRNA by approximately 105 nucleotides 12 h after T3 treatment,
      followed by a return to basal levels at 24 h. Primer extension analysis and
      Northern hybridization with 5'-untranslated region probes revealed no change in
      P450R mRNA 5' structure with T3 treatment. By contrast, RNase H analysis revealed
      a transient, T3-induced increase in P450R mRNA poly(A) tail, from approximately
      100 to approximately 205 A. This increase in P450R polyadenylation, detectable in
      the nucleus 8 h after T3 treatment and in the cytoplasm at 12 h, was transient
      and was reversed by 16 h, when the T3-induced accumulation of cytoplasmic P450R
      mRNA was near maximal. Actinomycin D blocked the increase in P450R poly(A) tail
      and the induction of P450R mRNA, indicating a requirement for ongoing gene
      transcription for both T3 responses. T3 treatment destabilized P450R mRNA in rat
      liver in vivo, as shown by the T3-dependent 6-fold decrease in cytoplasmic P450R
      mRNA half-life, from a basal value of >or=16 h in uninduced liver to
      approximately 2.5 h, measured 24 h after T3 administration. These findings
      demonstrate that T3 increases nuclear polyadenylation of P450R RNA as a
      transient, early regulatory response and that this response is temporally
      dissociated from the subsequent decrease in cytoplasmic P450R mRNA stability.

PMID- 11961127
TI  - Up-regulation of glutamate receptors in nucleus tractus solitarii underlies
      potentiation of baroreceptor reflex by heat shock protein 70.
AB  - Whereas induction of the 70-kDa heat shock protein (HSP70) in the nucleus tractus
      solitarii (NTS), the terminal site in the brain stem for primary baroreceptor
      afferents, augments baroreceptor reflex (BRR) response, the underlying cellular
      and molecular mechanism is essentially unexplored. In Sprague-Dawley rats, we
      evaluated the hypothesis that HSP70 may potentiate BRR response by up-regulating
      the molecular synthesis and functional expression of glutamate receptors in the
      NTS. Animals subjected to brief hyperthermic heat shock (HS; 42 degrees C for 15
      min) exhibited augmented expression of NR1 or NR2A subunit of N-methyl-D
      aspartate (NMDA) receptors, GluR1 or GluR4 subunits of alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate receptors and KA1 subunit of kainate receptors in
      the NTS. Intriguingly, this up-regulation of glutamate receptors was preceded by
      an increase in HSP70 expression at the NTS. The HS-induced augmentation in
      responsiveness of barosensitive NTS neurons to transient hypertension or
      potentiation of BRR response was discernibly blunted by MK-801 or 6-cyano-7
      nitroquinoxaline-2,3-dione. Bilateral microinjection into the NTS of an antisense
      hsp70 oligonucleotide (50 pmol) before HS significantly suppressed the induced
      expression of HSP70 or the increase in glutamate receptor subunits in the dorsal
      medulla and discernibly attenuated the potentiation of BRR response. Control
      microinjection into the NTS of sense or scrambled hsp70 oligonucleotide (50 pmol)
      was ineffective. These findings suggest that HSP70 induced by HS may enhance BRR
      response by up-regulating the molecular synthesis and functional expression of
      NR1 or NR2A subunit of NMDA receptors and GluR1, GluR4, or KA1 subunit of non
      NMDA receptors in the NTS.

PMID- 11961128
TI  - Ethylbromide tamoxifen, a membrane-impermeant antiestrogen, activates smooth
      muscle calcium-activated large-conductance potassium channels from the
      extracellular side.
AB  - Smooth-muscle calcium-activated large-conductance potassium channels (BK
      channels) are activated by tamoxifen and 17-beta-estradiol. This increase in
      NP(o), the number of channels, N, multiplied by open probability, depends on the
      presence of the regulatory beta1-subunit. Furthermore, a previous study indicated
      that 17-beta-estradiol might bind an extracellular site on the beta1-subunit.
      Because tamoxifen and 17-beta-estradiol may share a common binding site, we
      hypothesized that tamoxifen activates BK channels through a site on the
      extracellular surface of the membrane. A membrane-impermeant analog of tamoxifen,
      ethylbromide tamoxifen, was synthesized and used to test this hypothesis in whole
      cell, outside-out, cell-attached, and inside-out patches from canine colonic
      smooth muscle cells. Ethylbromide tamoxifen is positively charged and is
      therefore membrane-impermeant. In whole-cell experiments, ethylbromide tamoxifen
      increased K(+) current at potentials positive to +40 mV, which has previously
      been attributed to BK channels. Unlike tamoxifen, ethylbromide tamoxifen did not
      inhibit delayed rectifier current. In outside-out patches, ethylbromide tamoxifen
      increased BK channel NP(o) with an EC(50) value of 1 microM. Ethylbromide
      tamoxifen did not increase BK channel NP(o) in cell-attached or inside-out
      patches; however, subsequent addition of equimolar tamoxifen did. Both drugs
      diminished BK channel unitary conductance to a degree that paralleled the effect
      on NP(o), suggesting an additional interaction with the pore-forming alpha
      subunit. An interaction of tamoxifen with the pore was supported by a right shift
      in the concentration-response curve for tetraethylammonium; similar results were
      evident with iberiotoxin and charybdotoxin block. Our data suggest that
      ethylbromide tamoxifen does not easily traverse the plasma membrane and that
      tamoxifen binding responsible for activation of BK channels is at an
      extracellular site. The tamoxifen binding site may be within the extracellular
      loop of the BK channel beta1-subunit or, alternatively, on an as-yet-unidentified
      mediator that has an extracellular binding site.

PMID- 11961129
TI  - Metabotropic glutamate receptor 1 internalization induced by muscarinic
      acetylcholine receptor activation: differential dependency of internalization of
      splice variants on nonvisual arrestins.
AB  - In this study, we characterized the glutamate- or second-messenger kinase
      dependent internalization of the rat metabotropic glutamate receptor 1 (mGluR1)
      splice variants 1a, 1b, and 1c, and assessed the arrestin and dynamin dependence
      of these processes. To facilitate this we inserted a hemagglutinin epitope tag in
      the extracellular N-terminal domain of the splice variants. Quantification of
      glutamate-induced mGluR1 splice variant internalization provided by enzyme-linked
      immunosorbent assay and confirmed by immunofluorescent microscopy indicated that
      each splice variant underwent rapid internalization, which was strongly inhibited
      by coexpression of dominant-negative mutant (DNM) arrestin or dynamin. In
      addition glutamate-induced rapid translocation of arrestin-2-green fluorescent
      protein (GFP) or arrestin-3-GFP from cytosol to membrane was observed in cells
      expressing mGluR1 splice variants. Glutamate-induced internalization of mGluR1a
      and mGluR1c was partially blocked by a selective inhibitor of protein kinase C
      (PKC), 2-[1-(3-dimethylamino-propyl)indol-3-yl]-3-(1H-indol-3-yl)maleimide (GF
      109203X), whereas mGluR1b internalization was not significantly affected by this
      inhibitor. Similarly, inositol phosphate production after glutamate-induced
      activation of mGluR1a and mGluR1c was increased after PKC inhibition, whereas
      glutamate-induced mGluR1b stimulation was unaffected. Activation by carbachol of
      endogenously expressed M(1) muscarinic receptors in human embryonic kidney 293
      cells, induced the internalization of mGluR1 splice variants, which was partially
      blocked by pretreatment with inhibitors of either PKC or Ca(2+) calmodulin
      dependent kinase II (CaMKII). Expression of DNM-arrestin with mGluR1a or 1c
      strongly inhibited carbachol-induced internalization. However, coexpression of
      DNM-arrestin with mGluR1b was less effective in reducing carbachol-induced
      receptor internalization. In addition, arrestin-2-GFP or arrestin-3-GFP underwent
      significant carbachol-induced translocation from cytosol to membrane in cells
      coexpressing mGluR1a or 1c but not in cells coexpressing mGluR1b. This study
      demonstrates that the internalization of mGluR1 splice variants is subject to PKC
      and CaMKII regulation. In addition, regulation by these kinases confers
      differential arrestin dependence.

PMID- 11961130
TI  - Methamphetamine causes coordinate regulation of Src, Cas, Crk, and the Jun N
      terminal kinase-Jun pathway.
AB  - The clinical abuse of methamphetamine (METH) is a major concern because it can
      cause long-lasting neurodegenerative effects in humans. Current concepts of the
      molecular mechanisms underlying these complications have centered on the
      formation of reactive oxygen species. Herein, we provide cDNA microarray evidence
      that METH administration caused the induction of c-Jun and of other members
      involved in the pathway leading to c-Jun activation [stress-activated protein
      kinase/Jun N-terminal kinase (JNK3), Crk-associated substrate-Cas and c-Src]
      after environmental stresses or cytokine stimulation. Reverse transcription
      polymerase chain reaction analysis confirmed these increases and also showed that
      the expression of JNK1 and JNK3 but not JNK2 was also increased in the METH
      treated mice. Western blot analysis showed that METH increased the expression of
      c-Jun phosphorylated at serine-63 and serine-73 residues. Other upstream members
      of the JNK pathway, including phosphorylated JNKs, mitogen-activated protein
      kinase kinase 4, mitogen-activated protein kinase kinase 7, Crk II, Cas, and c
      Src were also increased at the protein level. These values returned to baseline
      by 1 week after drug treatment. These results are discussed in terms of their
      support for a possible role of the activation of the JNK/Jun pathway in the
      pathophysiological effects of METH.

PMID- 11961131
TI  - Five amino acids of the Xenopus laevis CRF (corticotropin-releasing factor) type
      2 receptor mediate differential binding of CRF ligands in comparison with its
      human counterpart.
AB  - The ligand selectivity of human (hCRF(2A)) and Xenopus laevis (xCRF(2)) forms of
      the corticotropin-releasing factor type 2 (CRF(2)) receptor differs. The purpose
      of this study was to identify amino acids in these two CRF(2) receptors
      conferring these differences. An amino acid triplet in the third extracellular
      domain (Asp(262)Leu(263)Val(264) in hCRF(2A) or Lys(264)Tyr(265)Ile(266) in
      xCRF(2)) was found to diverge between both receptors. When binding and signaling
      characteristics of receptor mutants hR2KYI and xR2DLV were assessed, the tri
      amino acid motif replacement produced receptors with binding properties
      resembling the xCRF(2) receptor. The converse mutation created a mutant receptor
      with a binding pharmacology identical to the profile of the hCRF(2A) receptor.
      This effect was most notable for xR2DLV, which possessed a binding affinity for
      astressin approximately 15-fold greater for astressin than sauvagine. In
      contrast, the binding profiles of the hCRF(2A) receptor and hR2KYI did not
      differ. These data indicate that another domain of the xCRF(2) receptor mediated
      low-affinity binding of astressin. Two amino acids in the first extracellular
      domain differ in xCRF(2) (Asp(69)Ser(70)) and hCRF(2A) (Glu(66)Tyr(67))
      receptors. The hCRF(2A) receptor mutant (hR2DS-KYI) bound astressin with a low
      affinity indistinguishable from the xCRF(2) receptor. Therefore, these data
      demonstrate that ligand selectivity differences between amphibian and human forms
      of the CRF(2A) receptor are governed by these two motifs of the extracellular
      domains of the xCRF(2) receptor.

PMID- 11961132
TI  - Lack of susceptibility of bicyclic nucleoside analogs, highly potent inhibitors
      of varicella-zoster virus, to the catabolic action of thymidine phosphorylase and
      dihydropyrimidine dehydrogenase.
AB  - The susceptibility of the bicyclic nucleoside analogs (BCNAs), highly potent and
      selective inhibitors of varicella-zoster virus (VZV), to the enzymes involved in
      nucleoside/nucleobase catabolism has been investigated in comparison with the
      established anti-VZV agent (E)-5-(2-bromovinyl)-2'-deoxyuridine [BVDU; brivudine
      (Zostex)]. Whereas human and bacterial thymidine phosphorylases (TPases)
      efficiently converted BVDU to its antivirally inactive free base (E)-5-(2
      bromovinyl)uracil (BVU), BCNAs showed no evidence of conversion to the free base
      in the presence of these enzymes. The lack of substrate affinity of TPase for the
      BCNAs could be rationalized by computer-assisted molecular modeling of the BCNAs
      in the TPase active site. Moreover, in contrast with BVU, which is a potent and
      selective inhibitor of dihydropyrimidine dehydrogenase (DPD) (50% inhibitory
      concentration; 10 microM in the presence of a 25 microM concentration of the
      natural substrate thymine), the free base (Cf 1381; 6-octyl-2,3-dihydrofuro[2,3
      d]pyrimidin-2-one) of BCNA (Cf 1368; 3-(2'-deoxy-beta-D-ribofuranosyl)-6-octyl
      2,3-dihydrofuro[2,3-d]pyrimidin-2-one) and the free base Cf 2200 [6-(4-n
      pentylphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one] of BCNA (Cf 1743; 3-(2'
      deoxy-beta-D-ribofuranosyl)-6-(4-n-pentylphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin
      2-one) did not inhibit the DPD-catalyzed catabolic reaction of pyrimidine bases
      (i.e., thymine) and pyrimidine base analogs [i.e., 5-fluorouracil (FU)] at a
      concentration of 250 microM. Consequently, whereas BVU caused a dramatic rise of
      FU levels in FU-treated mice, the BCNAs did not affect FU levels in such mice.
      From our data it is evident that BCNAs represent highly stable anti-VZV compounds
      that are not susceptible to breakdown by nucleoside/nucleobase catabolic enzymes
      and are not expected to interfere with cellular catabolic processes such as those
      involved in FU catabolism.

PMID- 11961133
TI  - Native CYP2C11: heterologous expression in Saccharomyces cerevisiae reveals a
      role for vacuolar proteases rather than the proteasome system in the degradation
      of this endoplasmic reticulum protein.
AB  - Cytochromes P450 (P450s) are hemoprotein enzymes committed to the metabolism of
      chemically diverse endo- and xenobiotics. They are anchored to the endoplasmic
      reticulum (ER) membrane with the bulk of their catalytic domain exposed to the
      cytosol, and thus they constitute excellent examples of integral monotopic ER
      proteins. Physiologically they are known to turn over asynchronously, but the
      determinants that trigger their proteolytic disposal and the pathways for such
      cellular disposal are not well defined. We recently showed that CYP3A4, the
      dominant human liver drug-metabolizing enzyme, and its rat liver orthologs
      undergo ubiquitin-dependent 26S proteasomal degradation not only after suicide
      inactivation, but also when CYP3A4 is expressed in Saccharomyces cerevisiae,
      presumably in its "native" form. The latter findings, obtained by the use of
      strains either with compromised proteasomal degradation of 3-hydroxy-3
      methylglutaryl-CoA reductase (HMGR) or deficient in ubiquitin-conjugating enzymes
      (Ubc; UBC), revealed that this native monotopic P450 enzyme, in common with the
      polytopic HMGR, required the function of certain HRD (HMGR degradation) and UBC
      genes. In this study, we examined the degradation of CYP2C11, a male rat liver
      specific P450, by heterologous expression in S. cerevisiae under comparable
      conditions. We report that unlike CYP3A4 and HMGR, the degradation of CYP2C11 in
      S. cerevisiae is independent of either HRD or UBC gene function, but it is
      largely dependent on vacuolar (lysosomal) proteolysis. These findings with two
      monotopic ER hemoproteins, CYP2C11 and CYP3A4, and the polytopic ER protein HMGR
      attest to the remarkable mechanistic diversity of cellular proteolytic disposal
      of ER proteins.

PMID- 11961134
TI  - A G-quadruplex-interactive potent small-molecule inhibitor of telomerase
      exhibiting in vitro and in vivo antitumor activity.
AB  - The telomerase complex is responsible for telomere maintenance and represents a
      promising cancer therapeutic target. We describe herein the antitelomerase and
      antitumor properties of a small-molecule compound designed by computer modeling
      to interact with and stabilize human G-quadruplex DNA, a structure that may form
      with telomeric DNA, thereby inhibiting access to telomerase. The 3,6,9
      trisubstituted acridine 9-[4-(N,N-dimethylamino)phenylamino]-3,6-bis(3
      pyrrolodinopropionamido) acridine (BRACO19) represents one of the most potent
      cell-free inhibitors of human telomerase yet described (50% inhibitory
      concentration of 115 +/- 18 nM). Moreover, in contrast to G-quadruplex
      interactive agents described previously, BRACO19 did not cause nonspecific acute
      cytotoxicity at similar concentrations to those required to completely inhibit
      telomerase activity. There exists a 90-fold differential (mean 50% inhibitory
      concentration for acute cell kill across seven human tumor cell lines of 10.6 +/-
      0.7 microM). The exposure of 21NT human breast cancer cells, which possess
      relatively short telomeres, to nonacute cytotoxic concentrations of BRACO19 (2
      microM) resulted in a marked reduction in cell growth after only 15 days. This
      was concomitant with a reduction in intracellular telomerase activity and onset
      of senescence as indicated by an increase in the number of beta-galactosidase
      positive-staining cells. Intraperitoneal administration of nontoxic doses of
      BRACO19 (2 mg/kg) to mice bearing advanced stage A431 human vulval carcinoma
      subcutaneous xenografts and previously treated with paclitaxel induced a
      significant increase in antitumor effect compared with that observed with
      paclitaxel alone. BRACO19 thus represents the first of a "second generation" of G
      quadruplex-mediated telomerase/telomere-interactive compounds. It possesses
      nanomolar potency against telomerase but low nonspecific cytotoxicity, growth
      inhibitory effects, and induction of senescence in a human breast cancer cell
      line and, moreover, significant antitumor activity in vivo when administered post
      paclitaxel to mice bearing a human tumor xenograft carcinoma.

PMID- 11961135
TI  - Regulation of fibronectin fibrillogenesis by protein kinases in cultured rat
      osteoblasts.
AB  - Fibronectin (Fn) plays an important role in the regulation of adhesion,
      migration, and maturation of osteoblasts. Fn fibrillogenesis is involved in the
      process of bone mineralization. To elucidate the regulatory role of protein
      kinases in the formation of fibrillar Fn matrix, Fn synthesis and assembly were
      examined in cultured osteoblasts. Osteoblasts assembled the endogenously released
      soluble Fn into immobilized form on the substratum in a time-dependent manner.
      Both 12-O-tetradecanoylphorbol-13 acetate (TPA) and forskolin increased the
      synthesis of Fn. However, the extracellular assembly of Fn fibril from both
      endogenously released and exogenously applied soluble Fn was increased by TPA but
      decreased by forskolin. Protein kinase C (PKC) inhibitors, such as H7, Ro 318220,
      and Go 6976, inhibited Fn fibrillogenesis. These results suggest that the dynamic
      of Fn fibrillogenesis is differentially regulated by the activation of PKC and
      protein kinase A (PKA). Both classic and novel isoforms of PKC are involved in
      the action of TPA in osteoblasts. It has been reported that alpha5beta1 integrin
      is related to Fn fibrillogenesis. Immunocytochemistry and flow cytometry showed
      that TPA and forskolin increased and inhibited, respectively, the clustering and
      surface expression of alpha5 integrins. TPA and forskolin did not affect protein
      levels of alpha5 integrins. The Western blot and reverse transcriptase-polymerase
      chain reaction showed that protein and mRNA levels of beta1 integrins also were
      not affected by TPA and forskolin. These results suggest that TPA and forskolin
      may affect the surface expression of alpha5beta1 integrins. cAMP response element
      binding protein phosphorylation is involved in the action of forskolin but not
      that of TPA. Our results suggest that PKC activation enhanced Fn fibrillogenesis,
      whereas PKA activation inhibited extracellular Fn fibrillogenesis in primary
      cultured osteoblasts. Cytosolic Fn synthesis and extracellular Fn assembly may be
      differentially regulated by the activation of PKA.

PMID- 11961136
TI  - Identification of albumin precursor protein, Phi AP3, and alpha-smooth muscle
      actin as novel components of redox sensing machinery in vascular smooth muscle
      cells.
AB  - Aerobic organisms are continually subjected to environmental stressors that
      compromise redox homeostasis and induce cellular injury. In vascular smooth
      muscle cells (vSMCs), the activation/repression of redox-regulated genes after
      environmental stress often involves protein binding to cis-acting antioxidant
      response elements (AREs). The present study was conducted to identify proteins
      that participate in redox-regulated protein binding to human c-Ha-ras and mouse
      glutathione S-transferase A1 AREs in vSMCs after oxidant injury. Challenge of
      vSMCs with 0.3 or 3 microM hydrogen peroxide, 3-methylcholanthrene,
      benzo[a]pyrene-7,8-diol, 3-hydroxy benzo[a]pyrene, and benzo[a]pyrene-3,6-quinone
      induced concentration-related increases in ARE protein binding. The profiles of
      ARE complex assembly were comparable, but exhibited chemical specificity.
      Pretreatment with 0.5 mM N-acetylcysteine inhibited activation of ARE protein
      binding in hydrogen peroxide-treated cells. Preparative electrophoretic mobility
      shift assays coupled to Western analysis identified NF-E2-related proteins 1 and
      2 and JunD in complexes assembled on AREs. Polyethylenimine affinity and sequence
      specific serial immobilized DNA affinity chromatography followed by N-terminal
      sequencing identified albumin precursor protein, phi AP3, and alpha-smooth muscle
      actin as members of the ARE signaling pathway. Sequence analysis of albumin
      protein revealed homology to the redox-regulated transcription factors Bach1 and
      2, as well as cytoskeletal and molecular motor proteins. These results implicate
      albumin precursor protein, phi AP3, and alpha-smooth muscle actin as participants
      in redox sensing in vSMCs, and suggest that protein complex assembly involves
      interactions between leucine zipper and zinc finger transcription factors with
      cytoskeletal proteins.

PMID- 11961137
TI  - Substrate-induced up-regulation of aldose reductase by methylglyoxal, a reactive
      oxoaldehyde elevated in diabetes.
AB  - Methylglyoxal (MG), a reactive dicarbonyl produced during glucose metabolism,
      induced a dose- and time-dependent increase in aldose reductase (AR) mRNA level
      in rat aortic smooth muscle cells (SMCs). AR has been implicated in the
      pathogenesis of diabetic complications, whereas the clinical efficacy of AR
      inhibitors has not been unequivocally proven. The enzyme catalyzes the reduction
      of glucose in the polyol pathway, as well as that of MG, which is known to be a
      preferred substrate of AR. A maximum of 4.5-fold induction of AR mRNA by MG was
      accompanied by elevated enzyme activity and protein levels and was completely
      abolished in the presence of cycloheximide or actinomycin D. Pretreatment of SMCs
      with N-acetyl-L-cysteine significantly suppressed the MG-induced AR expression,
      whereas DL-buthionine-(S,R)-sulfoximine further augmented the MG-induced increase
      in AR mRNA level. Intracellular levels of reactive oxygen species determined
      using 2',7'-dichlorofluorescein diacetate were significantly elevated in SMCs
      treated with MG, suggesting the involvement of oxidative stress in this process.
      However, inconsistent with our previous findings on oxidative stress-induced up
      regulation of AR, the inhibition of extracellular signal-regulated kinase by 2'
      amino-3'-methoxyflavone (PD98059) did not affect MG-induced AR expression,
      whereas blockade of the p38 mitogen-activated protein kinase pathway by 4-(4
      fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl) imidazol (SB203580)
      significantly suppressed the induction. The cytotoxic effect of MG on SMCs was
      significantly enhanced in the presence of the AR inhibitor ponalrestat,
      indicating a protective role of AR against MG-induced cell damage. Taken
      together, these observations indicated that substrate-induced induction of AR by
      MG during hyperglycemic conditions may hinder vascular remodeling and accelerate
      the development of vascular lesions in diabetes.

PMID- 11961138
TI  - Critical molecular determinants of voltage-gated sodium channel sensitivity to mu
      conotoxins GIIIA/B.
AB  - GIIIA/B mu-conotoxins block the rat skeletal muscle sodium channel (rNa(v)1.4)
      with high affinity by binding to specific residues in the pore. However, human
      Na(v)1.4 (hNa(v)1.4) channels, which are resistant to block by GIIIA/B, have
      these same pore residues. We used chimera constructs, site-directed mutagenesis,
      and electrophysiological techniques to investigate which residues determine
      GIIIA/B selectivity. Exchange of serine 729 in the D2/S5-S6 linker of rat
      Na(v)1.4 with leucine (S729L), the corresponding residue in hNa(v)1.4, reduces
      the sensitivity of rNa(v)1.4 by approximately 20-fold and largely accounts for
      the differential sensitivity of rNa(v)1.4 and hNa(v)1.4 to both GIIIA and GIIIB.
      To determine whether D2/S5-S6 linker residues might contribute to the resistance
      of neuronal channels to GIIIA/B, we exchanged residues in this linker that
      differed between rNa(v)1.4 and neuronal channels. Substitution of aspargine 732
      with lysine (N732K), the corresponding residue in rNa(v)1.1a and rNa(v)1.7,
      reduced the GIIIB sensitivity of rNa(v)1.4 by approximately 20-fold. The N732K
      substitution, however, only reduced GIIIA sensitivity of rNa(v)1.4 by
      approximately 4-fold, demonstrating that GIIIA and GIIIB have distinct
      interactions with the D2/S5-S6 linker. Our data indicate that naturally occurring
      variants in the extra-pore region of the D2/S5-S6 linker contribute to the
      isoform-specific sensitivity of sodium channels to GIIIA/B. Because S729 and N732
      are not part of the high-affinity binding site for mu-conotoxins, these extra
      pore residues probably influence the accessibility of the toxin to the binding
      site within the pore and/or the stability of the toxin-channel complex. Our
      results should aid the development of toxins that block specific neuronal sodium
      channel isoforms.

PMID- 11961139
TI  - The critical role of transmembrane prolines in human prostacyclin receptor
      activation.
AB  - The human prostacyclin receptor (hIP), a G protein-coupled receptor (GPCR), plays
      important roles in vascular smooth muscle relaxation as well as the prevention of
      platelet aggregation. It has been postulated that GPCR transmembrane (TM)
      prolines serve as molecular hinges or swivels and are necessary for proper
      binding and activation. By individually (as well as collectively) mutating these
      hIP prolines to alanine, the ability to form key structural and functional
      configurations was removed. Significant effects on both binding and activation
      were observed. Two highly conserved prolines across GPCRs, Pro-154, and Pro-254
      (TMVI), showed the greatest effect on decreasing both binding and activation when
      changed to alanine. Along the extracellular boundary of the highly conserved
      transmembrane III domain, a proline-to-alanine mutation at position 89 (P89A)
      revealed normal binding affinity in comparison with the 1D4-epitope-tagged hIP
      (hIP1D4) wild-type control (K(i), iloprost = 3 +/- 2 versus 7 +/- 3 nM,
      respectively). In contrast, activation was markedly affected, with an EC(50) of
      12.0 +/- 2.5 nM compared with that of 1.2 +/- 0.3 nM (10-fold difference) for the
      hIP1D4. Movement within TMIII has been shown to be necessary for effective GPCR
      activation. Both the extracellular location (above the putative binding pocket)
      along with an exclusive effect upon activation suggest that this movement is
      facilitated by the presence of Pro-89 and independent from the actions of ligand
      binding. This finding strongly supports a model in which proline residues serve
      as molecular hinges or swivels, essential for coupling receptor binding to
      activation.

PMID- 11961140
TI  - Enhanced detection of receptor constitutive activity in the presence of
      regulators of G protein signaling: applications to the detection and analysis of
      inverse agonists and low-efficacy partial agonists.
AB  - Fusion proteins between the human 5-hydroxytryptamine (5-HT)(1A) receptor and
      either wild type or certain pertussis toxin-resistant forms of G(o1)alpha and
      G(i1)alpha display constitutive GTPase activity that can be inhibited by the
      inverse agonist spiperone. Addition of recombinant regulator of G protein
      signaling (RGS) 1 or RGS16 to membranes expressing these fusion proteins resulted
      in elevation of this constitutive GTPase activity without significantly altering
      the binding affinity of antagonist/inverse agonist ligands. For a 5-HT(1A)
      receptor-(Cys(351)Ile)G(o1)alpha fusion protein the increase in basal GTPase
      activity was greater than 4-fold. Enzyme kinetic analysis demonstrated that the
      effect of RGS1 was as a GTPase-activating protein for the fusion construct. In
      the presence of the RGS proteins, both agonists and inverse agonists produced
      much more robust regulation of high-affinity GTPase activity than in their
      absence. This allowed detection of the partial agonist nature of WAY100635, which
      has been described previously as a neutral antagonist at the 5-HT(1A) receptor.
      Of a range of ligands studied, only haloperidol functioned as a neutral ligand in
      the presence of RGS1. These studies show that addition of a recombinant RGS
      protein provides a simple and novel means to elevate the fraction of basal
      membrane GTPase activity contributed by the constitutive activity of a receptor.
      By so doing, it also greatly enhances the ability to detect and analyze the
      effects of inverse agonists and to discriminate between neutral ligands and those
      with low levels of positive intrinsic efficacy.

PMID- 11961142
TI  - Maleimide is a potent inhibitor of topoisomerase II in vitro and in vivo: a new
      mode of catalytic inhibition.
AB  - Maleimide, N-ethyl-maleimide (NEM), and N-methyl-maleimide (NMM) were identified
      as potent catalytic inhibitors of purified human topoisomerase IIalpha, whereas
      the ring-saturated analog succinimide was completely inactive. Catalytic
      inhibition was not abrogated by topoisomerase II mutations that totally abolish
      the effect of bisdioxopiperazine compounds on catalytic inhibition, suggesting a
      different mode of action by these maleimides. Furthermore, in DNA cleavage assay
      maleimide and NEM could antagonize etoposide-induced DNA double-strand breaks.
      Consistently, maleimide could antagonize the effect of topoisomerase II poisons
      in three different in vivo assays: 1) In an alkaline elution assay maleimide
      protected against etoposide-induced DNA damage. 2) In a band depletion assay
      maleimide reduced etoposide-induced trapping of topoisomerase IIalpha and beta on
      DNA. 3) In a clonogenic assay maleimide antagonized the cytotoxicity of etoposide
      and daunorubicin on four different cell lines of human and murine origin. at-MDR
      cell lines with reduced nuclear topoisomerase IIalpha content are fully sensitive
      to maleimide, indicating that it is not a topoisomerase II poison in vivo. Our
      finding that topoisomerase II is sensitive to maleimide, NMM, and NEM but
      insensitive to succinimide demonstrates a strict requirement for the unsaturated
      ring bond for activity. We suggest that the observed antagonism in vitro and in
      vivo is caused by covalent modification of topoisomerase II cysteine residues
      reducing the amount of catalytically active enzyme sensitive to the action of
      topoisomerase II poisons.

PMID- 11961141
TI  - The nicotinic allosteric potentiating ligand galantamine facilitates synaptic
      transmission in the mammalian central nervous system.
AB  - In this study, the patch-clamp technique was used to determine the effects of
      galantamine, a cholinesterase inhibitor and a nicotinic allosteric potentiating
      ligand (APL) used for treatment of Alzheimer's disease, on synaptic transmission
      in brain slices. In rat hippocampal and human cerebral cortical slices, 1 microM
      galantamine, acting as a nicotinic APL, increased gamma-aminobutyric acid (GABA)
      release triggered by 10 microM acetylcholine (ACh). Likewise, 1 microM
      galantamine, acting as an APL on presynaptically located nicotinic receptors
      (nAChRs) that are tonically active, potentiated glutamatergic or GABA-ergic
      transmission between Schaffer collaterals and CA1 neurons in rat hippocampal
      slices. The cholinesterase inhibitors rivastigmine, donepezil, and metrifonate,
      which are devoid of nicotinic APL action, did not affect synaptic transmission.
      Exogenous application of ACh indicated that high and low levels of nAChR
      activation in the Schaffer collaterals inhibit and facilitate, respectively,
      glutamate release onto CA1 neurons. The finding then that the nAChR antagonists
      methyllycaconitine and dihydro-beta-erythroidine facilitated glutamatergic
      transmission between Schaffer collaterals and CA1 neurons indicated that in a
      single hippocampal slice, the inhibitory action of strongly, tonically activated
      nAChRs in some glutamatergic fibers prevails over the facilitatory action of
      weakly, tonically activated nAChRs in other glutamatergic fibers synapsing onto a
      given neuron. Galantamine is known to sensitize nAChRs to activation by low, but
      not high agonist concentrations. Therefore, at 1 microM, galantamine is likely to
      increase facilitation of synaptic transmission by weakly, tonically activated
      nAChRs just enough to override inhibition by strongly, tonically activated
      nAChRs. In conclusion, the nicotinic APL action can be an important determinant
      of the therapeutic effectiveness of galantamine.

PMID- 11961143
TI  - Supersensitivity of human metabotropic glutamate 1a receptor signaling in L929sA
      cells.
AB  - The effect of antagonist pretreatment on the signaling properties of the human
      metabotropic glutamate 1a (hmGlu1a) receptor was examined in stably transfected
      L929sA cells. Pre-exposure of hmGlu1a receptor-expressing cells to the mGlu1
      receptor antagonists (S)-4-carboxy-3-hydroxyphenylglycine and 7
      (hydroxyimino)cyclo-propa[b]chromen-1a-carboxylate ethyl ester dramatically
      enhanced subsequent glutamate-induced phosphoinositide hydrolysis and
      intracellular [Ca(2+)] rise. We found clear indications that the antagonist
      mediated enhancement of glutamate-evoked mGlu1a receptor signaling is caused by
      the development of mGlu1a receptor supersensitivity: the potency of glutamate was
      increased by 3-fold after 24 h antagonist pretreatment and the potency of the
      antagonists was significantly decreased in antagonist-pretreated cells. The
      kinetic profile of the antagonist-mediated enhancement showed that the maximal
      increase in intracellular [Ca(2+)] was already reached after 30-min pretreatment,
      suggesting that de novo receptor synthesis is not involved in the process of
      mGlu1a receptor supersensitization. Glutamate-mediated phosphoinositide
      hydrolysis increased up to 24 h after antagonist treatment. Although it seemed
      likely that the hmGlu1a receptor could desensitize after activation by
      endogenously present glutamate, removal of glutamate from the extracellular
      medium with GPT resulted in a much smaller enhancement of glutamate
      responsiveness. Moreover, the magnitude of antagonist-mediated receptor
      supersensitivity was much larger than the magnitude of agonist-induced receptor
      desensitization. These results suggest that antagonist-evoked mGlu1 receptor
      supersensitivity is not merely the result of a blockade of agonist-induced
      desensitization. Finally, we found that antagonist pretreatment doubled the
      amount of receptors at the cell surface. Our findings are the first lines of
      evidence that prolonged antagonist treatment can supersensitize the hmGlu1a
      receptor. In view of the potential therapeutic application of mGlu1 receptor
      antagonists, it will be important to know whether these phenomena occur in vivo.

PMID- 11961144
TI  - Further insight into mechanism of action of clodronate: inhibition of
      mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing
      metabolite.
AB  - Bisphosphonates are currently the most important class of antiresorptive drugs
      used for the treatment of diseases with excess bone resorption. Recent studies
      have shown that bisphosphonates can be divided into two groups with distinct
      molecular mechanisms of action depending on the nature of the R(2) side chain.
      Alendronate, like other nitrogen-containing bisphosphonates, inhibits bone
      resorption and causes apoptosis of osteoclasts and other cells in vitro by
      preventing post-translational modification of GTP-binding proteins with
      isoprenoid lipids. Clodronate, a bisphosphonate that lacks a nitrogen, does not
      inhibit protein isoprenylation but can be metabolized intracellularly to a beta
      gamma-methylene (AppCp-type) analog of ATP, which is cytotoxic to macrophages in
      vitro. The detailed molecular basis for the cytotoxic effects of adenosine-5'
      [beta,gamma-dichloromethylene]triphosphate (AppCCl(2)p) has not been determined
      yet. We addressed this question by studying the effects of alendronate,
      clodronate, and the clodronate metabolite AppCCl(2)p on isolated mitochondria,
      mitochondrial fractions, and mitochondrial membrane potential in isolated human
      osteoclasts. We found that AppCCl(2)p inhibits mitochondrial oxygen consumption
      by a mechanism that involves competitive inhibition of the ADP/ATP translocase.
      Alendronate or the native form of clodronate did not have any immediate effect on
      mitochondria. However, longer treatment with liposome-encapsulated clodronate
      caused collapse of the mitochondrial membrane potential, although prominent
      apoptosis was a late event. Hence, inhibition of the ADP/ATP translocase by the
      metabolite AppCCl(2)p is a likely route by which clodronate causes osteoclast
      apoptosis and inhibits bone resorption.

PMID- 11961145
TI  - Restenosis after angioplasty.

PMID- 11961146
TI  - Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene
      therapy.
AB  - BACKGROUND: X-linked severe combined immunodeficiency due to a mutation in the
      gene encoding the common gamma (gamma(c)) chain is a lethal condition that can be
      cured by allogeneic stem-cell transplantation. We investigated whether infusion
      of autologous hematopoietic stem cells that had been transduced in vitro with the
      gamma(c) gene can restore the immune system in patients with severe combined
      immunodeficiency. METHODS: CD34+ bone marrow cells from five boys with X-linked
      severe combined immunodeficiency were transduced ex vivo with the use of a
      defective retroviral vector. Integration and expression of the gamma(c) transgene
      and development of lymphocyte subgroups and their functions were sequentially
      analyzed over a period of up to 2.5 years after gene transfer. RESULTS: No
      adverse effects resulted from the procedure. Transduced T cells and natural
      killer cells appeared in the blood of four of the five patients within four
      months. The numbers and phenotypes of T cells, the repertoire of T-cell
      receptors, and the in vitro proliferative responses of T cells to several
      antigens after immunization were nearly normal up to two years after treatment.
      Thymopoiesis was documented by the presence of naive T cells and T-cell antigen
      receptor episomes and the development of a normal-sized thymus gland. The
      frequency of transduced B cells was low, but serum immunoglobulin levels and
      antibody production after immunization were sufficient to avoid the need for
      intravenous immunoglobulin. Correction of the immunodeficiency eradicated
      established infections and allowed patients to have a normal life. CONCLUSIONS:
      Ex vivo gene therapy with gamma(c) can safely correct the immune deficiency of
      patients with X-linked severe combined immunodeficiency.

PMID- 11961147
TI  - Intravascular gamma radiation for in-stent restenosis in saphenous-vein bypass
      grafts.
AB  - BACKGROUND: Intracoronary radiation therapy is effective in reducing the
      recurrence of in-stent stenosis in native coronary arteries. We examined the
      effects of intravascular gamma radiation in patients with in-stent restenosis of
      saphenous-vein bypass grafts. METHODS: A total of 120 patients with in-stent
      restenosis in saphenous-vein grafts, the majority of whom had diffuse lesions,
      underwent balloon angioplasty, atherectomy, additional stenting, or a combination
      of these procedures. If the intervention was successful, the patients were
      randomly assigned in a double-blind fashion to intravascular treatment with a
      ribbon containing either iridium-192 or nonradioactive seeds. The prescribed
      dose, delivered at a distance of 2 mm from the source, was 14 to 15 Gy in vessels
      that were 2.5 to 4.0 mm in diameter and 18 Gy in vessels with a diameter that
      exceeded 4.0 mm. The primary end points were death from cardiac causes, Q-wave
      myocardial infarction, revascularization of the target vessel, and a composite of
      these events at 12 months. RESULTS: Revascularization and radiation therapy were
      successfully accomplished in all patients. At six months, the restenosis rate was
      lower in the 60 patients assigned to the iridium-192 group than in the 60
      assigned to the placebo group (21 percent vs. 44 percent, P=0.005). At 12 months,
      the rate of revascularization of the target lesion was 70 percent lower in the
      iridium-192 group than in the placebo group (17 percent vs. 57 percent, P<0.001),
      and the rate of major cardiac events was 49 percent lower (32 percent vs. 63
      percent, P<0.001). CONCLUSIONS: The results of our study support the use of gamma
      radiation therapy for the treatment of in-stent restenosis in patients with
      bypass grafts.

PMID- 11961148
TI  - Erythromycin-resistant group A streptococci in schoolchildren in Pittsburgh.
AB  - BACKGROUND: Resistance to erythromycin has been very uncommon among group A
      streptococci in the United States. METHODS: As part of a longitudinal study, we
      obtained surveillance throat cultures twice monthly and with each new respiratory
      tract illness from children in kindergarten through grade 8 at one school in
      Pittsburgh. Screening for resistance to erythromycin and clindamycin was
      initially accomplished with use of the Kirby-Bauer disk-diffusion test. The
      minimal inhibitory concentration of resistant isolates was determined by the E
      test. A double disk-diffusion test was used to characterize the resistance
      phenotype, and the polymerase-chain-reaction assay was used to identify the
      resistance gene. The molecular relatedness of strains was determined by field
      inversion gel electrophoresis. RESULTS: A total of 1794 throat cultures were
      obtained from 100 children between October 2000 and May 2001, of which 318
      cultures (18 percent) from 60 of the children were positive for group A
      streptococci. Forty-eight percent of these isolates (153 of 318) were resistant
      to erythromycin. None were resistant to clindamycin. Results of the double disk
      diffusion test indicated the presence of the M phenotype of erythromycin
      resistance. Molecular typing indicated that the outbreak was due to a single
      strain of group A streptococci. Of 100 randomly selected isolates of group A
      streptococci obtained from the community between April and June 2001, 38 were
      resistant to erythromycin. CONCLUSIONS: In January 2001, during a longitudinal
      study of schoolchildren, we detected the emergence of erythromycin resistance in
      pharyngeal isolates of group A streptococci. This clonal outbreak also affected
      the wider community.

PMID- 11961149
TI  - Development of Kaposi's sarcoma in a surgical wound.

PMID- 11961150
TI  - Image in clinical medicine. Coronary-artery fistula with a giant aneurysm.

PMID- 11961152
TI  - Nonalcoholic fatty liver disease.

PMID- 11961151
TI  - Schistosomiasis.

PMID- 11961153
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 12-2002. A 50-year-old man with eosinophilia and fluctuating
      hepatic lesions.

PMID- 11961154
TI  - Successful gene therapy for severe combined immunodeficiency.

PMID- 11961156
TI  - Macrolide-resistant group a streptococcus--now in the United States.

PMID- 11961157
TI  - Group psychosocial support in metastatic breast cancer.

PMID- 11961158
TI  - Cranial CT before lumbar puncture in suspected meningitis.

PMID- 11961159
TI  - HLA matching for hematopoietic stem-cell transplants.

PMID- 11961160
TI  - Mesenteric venous thrombosis.

PMID- 11961161
TI  - Severe hyperosmolar metabolic acidosis due to a large dose of intravenous
      lorazepam.

PMID- 11961163
TI  - Progress and problems in defining susceptibility genes for rheumatic diseases.

PMID- 11961162
TI  - The popliteal-artery entrapment syndrome in a patient using anabolic steroids.

PMID- 11961164
TI  - Family studies in systemic lupus erythematosus.

PMID- 11961165
TI  - The therapeutic uses of intravenous immunoglobulins in autoimmune rheumatic
      diseases.

PMID- 11961166
TI  - Sacral and iliac articular cartilage thickness and cellularity: relationship to
      subchondral bone end-plate thickness and cancellous bone density.
AB  - OBJECTIVES: To measure the thickness and cellularity of adult human sacral and
      iliac articular cartilages and the thickness and density of the subchondral
      bones. METHODS: The right sacroiliac joints of 15 adult patients were examined
      post-mortem. HOME (Highly Optimized Microscope Environment) microscopy was used
      to measure articular cartilage and subchondral bone end-plate thickness.
      Conventional morphometric techniques were employed to estimate cartilage
      cellularity and cancellous bone density. RESULTS: Sacral articular cartilage was
      thicker than iliac (1.81 vs 0.80 mm, P<0.001). Iliac cartilage cell density in
      all zones was higher than sacral. The overall mean was 31.19 x 10(-3) vs. 23.23 x
      10(-3)/mm(3), P<0.001. Superficial zones contained more cells than middle and
      deep zones but there were large differences between the cell numbers of the
      middle and deep zones of both sacral and iliac cartilages. Iliac subchondral bone
      end-plates were thicker than sacral (0.36 vs 0.23 mm, P<0.001). The thickness of
      these plates was related inversely to that of the overlying articular cartilages.
      Iliac subchondral cancellous bone was twice as dense as sacral (22.07 vs. 12.05%,
      P<0.001), a ratio recognized anteriorly, centrally and posteriorly. CONCLUSIONS:
      Adult human sacral cartilage is thick and of low cell density. It rests upon a
      thin bone end-plate supported by porous, cancellous bone. Iliac cartilage and
      bone display the converse proportions. The identification of these variables may
      assist understanding of normal sacroiliac joint function and the interpretation
      of tissue changes in the spondylarthropathies.

PMID- 11961167
TI  - The wafer test: a semi-quantitative test to screen for xerostomia.
AB  - OBJECTIVE: To develop a screening test for xerostomia. METHODS: A cross-sectional
      study was conducted among 152 healthy subjects aged <20-60 yr, 30 patients with
      primary Sjogren's syndrome and 60 patients with other connective tissue diseases,
      sampled randomly. A validated screening questionnaire for sicca syndrome and the
      Schirmer-1 and wafer tests were carried out in all subjects. In addition, non
      stimulated whole salivary flow was measured in a random sample of 113
      participants. The main outcome was the time of dissolution of the wafer. RESULTS:
      Time of dissolution of the wafer was 2.8+/-2.1 min in the healthy group, 3.3+/
      1.5 min in the connective tissue diseases group, and 9.2+/-3.9 min in the primary
      Sjogren's syndrome group (P<0.001). The correlation coefficient between the wafer
      test and non-stimulated whole salivary flow was -0.60 [95% confidence interval
      (CI) -0.47, -0.71]. A cut-off value of 4 min ('wafer 4') showed sensitivity of
      92.9%, specificity of 71.7%, a positive predictive value of 31.7%, a negative
      predictive value of 98.6%, accuracy of 74.3%, an ROC (receiver operating curve)
      value of 82.3 and a likelihood ratio of 3.3 (95% CI 2.3, 4.6) for xerostomia. The
      proportion of patients with wafer 4 was 8% in the healthy group, 23% in the
      connective tissue diseases group and 93% in the primary Sjogren's syndrome group
      (P<0.001). Wafer 4 was a significant predictor of xerostomia after controlling
      for age, gender, temperature and relative humidity. CONCLUSION: The wafer test is
      valid and reliable for identifying subjects with xerostomia.

PMID- 11961168
TI  - Who should have priority for a knee joint replacement?
AB  - OBJECTIVES: To explore patients' views on who should have priority for total knee
      replacement (TKR). METHODS: In-depth, semistructured interviews were conducted
      with 25 patients on the waiting list for a TKR. RESULTS: All participants were
      willing to comment on waiting lists and prioritization for TKR. Two major themes
      emerged: what they thought should happen, and what they thought did happen. They
      thought that priority should be based on length and degree of suffering, pain
      severity, immobility, paid employment, payment of National Insurance
      contributions, and caring for dependants. In contrast, they thought that what
      actually happened depended on age and weight, excessive complaining and access to
      private practice. CONCLUSIONS: The participants agreed with health professionals
      that pain and disability should be key criteria on which to prioritize people for
      a TKR. However, they also argued for a fair decision-making process that also
      included additional factors specific to the patient's circumstances. Criteria to
      aid prioritization for joint surgery need to accommodate the views of patients as
      well as professionals.

PMID- 11961169
TI  - Immune responses to native beta(2)-glycoprotein I in patients with systemic lupus
      erythematosus and the antiphospholipid syndrome.
AB  - OBJECTIVE: To identify HLA class II associations with anti beta(2)-glycoprotein I
      (beta2GPI) antibodies in a cohort of Caucasian patients with systemic lupus
      erythematosus (SLE) and to determine whether these HLA genotypes act as
      restriction elements for lymphocyte proliferation to native human beta2GPI in
      vitro. METHODS: Anti-beta2GPI antibodies were detected in patient sera using
      enzyme-linked immunosorbent assays (ELISAs). HLA class II alleles (DRB1, DQB1)
      were determined by polymerase chain reaction-based DNA genotyping. In vitro
      peripheral blood mononuclear cell (PBMC) responses to native human beta2GPI were
      measured in a 7-day proliferation assay. RESULTS: We identified three groups of
      Caucasian SLE patients using these ELISAs. In group 1, 16 out of 18 SLE patients
      (89%) with anti-beta2GPI antibodies were positive for HLA-DRB1*0401/4/8, DR11 or
      DRB1*1302 (P=0.001 vs controls) compared with 23 out of 53 patients (43%) in
      group 2 with anti-cardiolipin antibodies only, 57 out of 151 patients (38%) in
      group 3 (SLE patients without anticardiolipin antibodies) and 109 out of 225
      controls (48%). Fourteen patients with anti-beta2GPI antibodies had greater
      median stimulation indices to beta2GPI in vitro compared with the 15 controls
      studied (P=0.04). CONCLUSION: The HLA class II and PBMC proliferation data
      suggest that beta2GPI may be both a T- and B-cell autoantigen in SLE.

PMID- 11961170
TI  - Polymorphism in the immunoglobulin VH gene V1-69 affects susceptibility to
      rheumatoid arthritis in subjects lacking the HLA-DRB1 shared epitope.
AB  - OBJECTIVE: To investigate the contribution of polymorphism in the immunoglobulin
      heavy chain variable region V1-69 gene set to genetic susceptibility to
      rheumatoid arthritis (RA) in Czech and British patients. METHODS: We used V1-69
      gene sequence-specific polymerase chain reaction (PCR) and restriction enzyme
      digestion to study polymorphism in the V1-69 gene set in germline DNA of 109
      Czech and 159 British RA patients and 164 ethnically matched controls.
      Polymorphism was further studied by nucleotide sequencing of the V1-69 gene locus
      in germline DNA. RESULTS: We found that all patients and controls had at least
      one V1-69 gene copy. In the Czech RA cohort, the dimorphic nucleotide in codon 73
      of V1-69 (GAA or AAA) was present in the homozygous form 73(A/A) in 31 of 109
      (28.4%) RA patients vs 12 of 79 (15.2%) controls [odds ratio (OR)=2.22, P<0.001].
      When the RA patients and controls were classified according to HLA shared epitope
      (SE) status, 73(A/A) was found in 18 of 76 (23.7%) SE(+) patients compared with
      13 of 38 (34.2%) SE(-) patients, four of 12 (18.2) SE(+) controls and eight of 57
      (14%) SE(-) controls. This suggests that homozygosity for the dimorphic sequence
      73(A) contributed to susceptibility to RA in SE(-) Czech individuals (OR=3.2,
      P<0.001). The most striking observation was that none of the 38 SE(-) Czech
      patients, compared with 11 of 76 (14.5%) SE(+) RA patients, three of 22 (13.6%)
      SE(+) and 11 of 57 (19.3%) SE(-) ethnically matched controls, were homozygous for
      the alternative dimorphic sequence 73(G/G) (OR=9.1, P<0.05). These data, however,
      were not replicated in a Caucasoid British RA population. CONCLUSION: The
      dimorphic sequence at codon 73 (73(A/A)) of the V1-69 gene contributes to genetic
      susceptibility in SE(-) Czech RA patients.

PMID- 11961171
TI  - Neuropsychological function in systemic lupus erythematosus: a five-year
      longitudinal study.
AB  - OBJECTIVE: To evaluate potential changes in cognitive functions over a 5-yr
      period in patients with systemic lupus erythematosus (SLE). METHODS: Twenty-eight
      patients with SLE were examined at baseline and after a mean follow-up of 60.7+/
      5.0 months using standardized neuropsychological tests. Group changes in
      performance over time were measured and the effects of baseline values for
      subsequent changes in individual variables after 5 yr were evaluated. RESULTS:
      When all SLE patients were considered as a group, seven out of nine (78%)
      neuropsychological variables remained unchanged and two (22%) improved
      significantly during the observation period, possibly due to methodological bias.
      Analysis of the importance of the level of initial cognitive performance for
      subsequent changes during the observation period, demonstrated that cognitive
      changes were not significantly influenced by baseline levels, except for a trend
      in three of nine variables. Neither demographic nor disease-associated
      quantitative factors were associated with cognitive changes over time.
      CONCLUSION: Cognitive dysfunction seems to be a relatively stable feature of
      central nervous system involvement in SLE. A decrease in performance over time
      was not demonstrated consistently in the majority of domains.

PMID- 11961172
TI  - Dry eyes and mouth syndrome--a subgroup of patients presenting with sicca
      symptoms.
AB  - OBJECTIVE: To evaluate the characteristics of patients presenting with symptoms
      suggestive of Sjogren's syndrome (SS) but failing to satisfy diagnostic criteria.
      METHODS: Clinical, serological and histological data were collected on 34
      patients presenting with dry eyes and/or mouth who did not satisfy the Vitali
      criteria for the diagnosis of SS. They were compared with 136 patients with
      primary SS, 38 patients with secondary SS, and 13 patients without SS.
      Questionnaires on symptoms from each group were compared with 43 healthy
      controls. RESULTS: The 34 patients who did not satisfy the diagnostic criteria
      for SS or any other connective tissue disease were designated dry eyes and mouth
      syndrome (DEMS). Their demography including age was similar to that of a primary
      SS group and there was no more atrophy seen on their biopsies compared with SS
      and non-SS controls. They scored highly on visual analogue scales of symptoms but
      had few objective signs. All were negative for anti-Ro and anti-La although the
      prevalence of antinuclear antibodies (19%) was increased compared with a normal
      population. There was no excess of SS-associated tissue types. CONCLUSION: There
      was no evidence that age, salivary gland atrophy or subclinical SS accounted for
      the symptoms in DEMS. Most of the patients fitted into a spectrum of disease
      which tended more towards fibromyalgia and/or chronic fatigue syndrome.

PMID- 11961173
TI  - In polymyalgia rheumatica serum prolactin is positively correlated with the
      number of typical symptoms but not with typical inflammatory markers.
AB  - OBJECTIVES: Hyperprolactinaemia has been associated with the active phase of
      human systemic lupus erythematosus and rheumatoid arthritis. In the present
      study, we investigated the role of prolactin (PRL) in relation to the number of
      typical symptoms and serum markers of systemic inflammation in patients with
      polymyalgia rheumatica (PMR). METHODS: One hundred and two PMR patients presented
      with typical symptoms such as adynamia, bilateral muscular pain in shoulders,
      upper arms or neck, bilateral muscular pain in the pelvic girdle, headache,
      morning stiffness, arthralgia, symptoms of depression, fever, initial weight loss
      (>4 kg/month), and transient visual symptoms. If one of the mentioned symptoms
      was present, the corresponding item was scored with one point (maximum unweighted
      item points=10). PRL, interleukin-2 (IL-2), IL-6, IL-1 receptor antagonist (IL
      1ra), tumour necrosis factor (TNF), soluble IL-2 receptor (sIL-2R), and soluble
      vascular cell adhesion molecule (sVCAM) were measured by enzyme-linked
      immunosorbent assay in patients and 31 age-matched healthy controls. RESULTS:
      Fifteen PMR patients with elevated PRL had a higher number of symptoms as
      compared with patients with normal levels (P=0.003). PRL was correlated with the
      number of symptoms (all PMR patients: r(rank)=+0.380, P<0.001) and duration of
      morning stiffness (all PMR patients: r(rank)=+0.335, P=0.002) irrespective of
      prior corticosteroid treatment. However, PRL did not correlate with markers of
      systemic inflammation such as erythrocyte sedimentation rate, C-reactive protein,
      serum IL-1ra, IL-2, sIL-2R, IL-6, TNF, and sVCAM. CONCLUSION: The number of
      symptoms in PMR patients was positively correlated with PRL, but PRL was not
      correlated with serum markers of inflammation. This indicates that PRL is not a
      pro-inflammatory stimulus in patients with PMR. The inter-relationship between
      PRL and symptoms or duration of morning stiffness may be more a sign of central
      nervous system involvement, as it can be observed in people with depressed mood
      or under psychological stress.

PMID- 11961174
TI  - Drug survival, efficacy and toxicity of monotherapy with a fully human anti
      tumour necrosis factor-alpha antibody compared with methotrexate in long-standing
      rheumatoid arthritis.
AB  - OBJECTIVES: To compare the 48-week drug survival, efficacy and toxicity of
      monotherapy with a fully human anti-tumour necrosis factor-alpha (TNF-alpha)
      monoclonal antibody (moAb) and methotrexate (MTX) in patients with active long
      standing rheumatoid arthritis (RA). Secondary aims were to identify potential
      predictors for clinical response. METHODS: Patients with RA, enrolled in phase I
      trials with a human anti-TNF-alpha moAb and followed for at least 48 weeks at our
      centre, were compared with patients receiving MTX monotherapy without folate
      supplementation. The first 6 weeks of anti-TNF therapy were placebo-controlled
      and followed by an open-label study. Patients treated with MTX participated in a
      48-week, double-blind, phase III study of MTX alone vs MTX with folate
      supplementation, which was co-ordinated by our department. The studies with anti
      TNF-alpha and MTX were performed in the same period and had very similar
      inclusion, exclusion, response and stop criteria. RESULTS: Sixty-one patients
      treated with anti-TNF-alpha moAb were compared with 137 receiving MTX
      monotherapy. At baseline, patients in the anti-TNF-alpha group had a longer
      disease duration (median 108 vs 50 months, P=0.0001) and a more protracted
      history of second-line anti-rheumatic drugs than those treated with MTX (median 4
      vs 1, P=0.0001). The 48-week dropout rate was lower among patients treated with
      anti-TNF (23 vs 45% in the MTX group, P<0.005). Proportional hazard analysis
      showed a significantly lower dropout risk among anti-TNF-treated patients
      [relative risk (95% confidence interval): 0.28 (0.12-0.6) uncorrected and 0.17
      (0.06-0.45) corrected for confounders). The 48-week area under the curve for the
      disease activity score (DAS) was smaller in the anti-TNF-alpha group than in the
      MTX group (P=0.005). The percentage of responders was higher in the anti-TNF
      alpha group over the whole study period. The median percentage of visits in which
      a patient fulfilled the European League Against Rheumatism (EULAR) response
      criteria was 83% in the anti-TNF-alpha group vs 40% in the MTX group (P=0.0001).
      Clinical and demographic characteristics were, in general, poor predictors for
      response to therapy at week 48. The clinical response after the first anti-TNF
      alpha dose tended to increase the chance of prolonged efficacy of this approach
      [relative risk (95% confidence interval): 2 (0.75-6.0)]. The previous number of
      second-line drugs was the only predictive variable for response to MTX to which
      it was inversely related [relative risk (95% confidence interval): -0.71 (-0.57
      to -0.88)]. CONCLUSIONS: In patients with active, long-standing RA, blocking TNF
      alpha is more effective and better tolerated than MTX monotherapy. An early
      response increases the chance of a sustained effect of anti-TNF-alpha. In
      contrast to MTX, the response to anti-TNF-alpha is not affected by previous
      disease-modifying anti-rheumatic drug history.

PMID- 11961175
TI  - Primary Sjogren's syndrome associated with inclusion body myositis.
AB  - OBJECTIVE: To describe three new patients with inclusion body myositis (IBM)
      associated with primary Sjogren's syndrome (pSS) and summarize the clinical and
      serological picture for all six patients reported so far. PATIENTS AND METHODS:
      Three out of 518 (0.6%) pSS patients followed in our department over a period of
      15 yr (1985-2000) also presented IBM. The diagnosis was based on histological
      criteria. Previous reports described four more patients with IBM associated with
      pSS. Five out of six were females; the mean age of IBM onset was 53.3+/-14.0 yr
      and the disease duration 8.0+5.8 yr. RESULTS: Four out of six patients presented
      IBM several years after the onset of pSS. Four out of six patients presented
      extraglandular manifestations, such as arthralgias, vitamin B12 deficiency,
      interstitial kidney disease and biliary cirrhosis. The serological picture did
      not differ significantly from that observed in pSS alone. CONCLUSION: Although
      rare, IBM may be seen in patients with pSS and it affects predominantly women.
      The clinical and pathological pictures do not differ from those observed in
      idiopathic IBM. A common autoimmune pathway in these two diseases, but no
      definite conclusions can be drawn.

PMID- 11961176
TI  - No evidence of parvovirus B19, Chlamydia pneumoniae or human herpes virus
      infection in temporal artery biopsies in patients with giant cell arteritis.
AB  - OBJECTIVES: Recent studies have suggested that infective agents may be involved
      in the pathogenesis of giant cell arteritis (GCA), in particular Chlamydia
      pneumoniae and parvovirus B19. We investigated temporal arteries from patients
      with GCA for these infections as well as human herpes viruses using the
      polymerase chain reaction (PCR). METHODS: Thirty temporal artery biopsies from 30
      patients suspected of having GCA within a period of 1 yr were examined. Thirteen
      patients had classical GCA, two had biopsy-negative GCA, 10 patients had
      polymyalgia rheumatica and five patients had other conditions. DNA was extracted
      from frozen biopsies and PCR was used to amplify genes from Chlamydia pneumoniae,
      parvovirus B19 and each of the eight human herpes viruses: herpes simplex viruses
      HSV-1 and 2, Epstein-Barr virus, cytomegalovirus, varicella zoster virus and
      human herpes viruses HHV-6, -7 and -8. RESULTS: In all 30 biopsies, PCR was
      negative for DNAs of parvovirus B19, each of the eight human herpes viruses and
      C. pneumoniae. CONCLUSIONS: We found no evidence of DNA from parvovirus B19,
      human herpes virus or C. pneumoniae in any of the temporal arteries. These agents
      do not seem to play a unique or dominant role in the pathogenesis of GCA.

PMID- 11961177
TI  - A case-control study examining the role of physical trauma in the onset of
      fibromyalgia syndrome.
AB  - OBJECTIVE: To investigate whether physical trauma may precipitate the onset of
      fibromyalgia syndrome (FMS). DESIGN: A case-control study was carried out to
      compare fibromyalgia out-patients with controls attending non-rheumatology out
      patient clinics. METHOD: One hundred and thirty-six FMS patients and 152 age- and
      sex-matched controls completed a postal questionnaire about any physical trauma
      in the 6 months before the onset of their symptoms. RESULTS: Fifty-three (39%)
      FMS patients reported significant physical trauma in the 6 months before the
      onset of their disease, compared with only 36 (24%) of controls (P<0.007). There
      was no significant difference between FMS patients who had a history of physical
      trauma and those who did not have physical trauma with regard to age, sex,
      disease duration, employment status and whether their job at onset was manual.
      CONCLUSION: Physical trauma in the preceding 6 months is significantly associated
      with the onset of FMS.

PMID- 11961178
TI  - Sex hormonal factors and chronic widespread pain: a population study among women.
AB  - OBJECTIVE: The observation of higher rates of chronic widespread pain, the
      cardinal feature of fibromyalgia, in women has led to hypotheses about the role
      of sex hormonal factors in the aetiology of symptoms. There is little available
      evidence from epidemiological studies on their importance or role. METHODS: A
      population postal survey was carried out involving 1178 female participants
      living in south-east Cheshire in the north-west of England. RESULTS: Amongst pre-
      and peri-menopausal women, the risk of chronic widespread pain was unrelated
      either to the length of the menstrual cycle or the usual length of period
      reported by participants. Risk was similar in current users and non-users of the
      oral contraceptive pill, and amongst users there was no relationship with
      duration of use. However, the reporting of chronic widespread pain showed a
      relationship with total score on a premenstrual symptom questionnaire. However,
      this relationship was explained by pain symptoms. Amongst post-menopausal women,
      reporting chronic widespread pain was not related to age at menopause. An
      increased (but non-significant) risk of chronic widespread pain was associated
      with current hormone replacement therapy (HRT), which may be a consequence of HRT
      being prescribed for menopausal symptoms. CONCLUSION: This study, conducted on a
      large unselected population, has not demonstrated an association between sex
      hormonal factors and chronic widespread pain.

PMID- 11961179
TI  - Platelet function is inhibited by non-selective non-steroidal anti-inflammatory
      drugs but not by cyclo-oxygenase-2-selective inhibitors in patients with
      rheumatoid arthritis.
AB  - BACKGROUND: Interaction with platelet function by non-steroidal anti-inflammatory
      drugs (NSAIDs) is related to the inhibition of cyclo-oxygenase-1 (COX-1). In
      patients with rheumatoid arthritis (RA), only one of the COX-2-selective NSAIDs
      (nabumetone) has been demonstrated to spare platelet function partially.
      OBJECTIVE: To compare the effects of the COX-2-selective inhibitor, meloxicam,
      with those of the non-selective NSAID, naproxen, on platelet function and
      thromboxane levels in RA patients. METHODS: In this randomized, controlled, cross
      over trial, 10 RA patients used meloxicam 7.5 mg bid and naproxen 500 mg bid,
      each during a 2-week period. Washout periods were applied. Before and after each
      2-week period of NSAID intake, laboratory studies were performed. RESULTS:
      Platelet aggregation was significantly less influenced, thromboxane levels were
      less inhibited (246 vs 117 pg/ml) and bleeding times were less prolonged with
      meloxicam than with naproxen (3.2 vs 2.3 min). Moreover, the results of all tests
      during meloxicam exposure were comparable with baseline values. CONCLUSION: In RA
      patients, meloxicam, a representative of the selective COX-2 inhibitors, does not
      interfere with platelet function and thromboxane levels, in contrast with
      naproxen (a non-selective COX inhibitor).

PMID- 11961180
TI  - Tumour necrosis factor receptor II polymorphism and juvenile idiopathic
      arthritis.
AB  - OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a complex polygenic disorder.
      The encouraging outcome of anti-tumour necrosis factor (TNF) treatment, as well
      as serological studies, has implicated TNF and its receptors (TNFRI and TNFRII,
      or TNFRSF1B) in the pathogenesis of JIA. The purpose of this study was to
      investigate the exon 6 TNFRII single nucleotide polymorphism (SNP) in a well
      defined UK cohort of JIA patients, using case-control association analysis.
      METHODS: A total of 435 patients, spanning seven JIA subgroups, and 261 healthy
      individuals were screened for the polymorphism using the polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: No
      significant differences were observed between the SNP allelic or genotypic
      frequencies of patients and controls, or between JIA subgroups. CONCLUSIONS: This
      TNFRII exon 6 SNP does not seem to be associated with susceptibility to JIA.

PMID- 11961181
TI  - Immune complexes contain immunoglobulin A rheumatoid factor in serum and synovial
      fluid of patients with polyarticular juvenile rheumatoid arthritis.

PMID- 11961182
TI  - Acute lethal pancreatitis in childhood systemic lupus erythematosus.

PMID- 11961183
TI  - Neuromyelitis optica (Devic's syndrome) in systemic lupus erythematosus: a case
      report.

PMID- 11961184
TI  - Failure of G-CSF therapy in neutropenia associated with Sjogren's syndrome.

PMID- 11961185
TI  - Stevens-Johnson syndrome in association with hydroxychloroquine treatment for
      rheumatoid arthritis.

PMID- 11961186
TI  - Endochondral ossification in Achilles and patella tendinopathy.

PMID- 11961187
TI  - Urticarial vasculitis: a paraneoplastic presentation of B-cell non-Hodgkin's
      lymphoma.

PMID- 11961190
TI  - The trust factor.

PMID- 11961191
TI  - Sleeping with the enemy: treatment of fatigue in individuals with cancer.

PMID- 11961192
TI  - Breast cancer prevention.

PMID- 11961193
TI  - Prevention in the balance.

PMID- 11961194
TI  - Viral oncolysis.
AB  - The concept of using replicating viruses as anticancer agents is not a new one,
      but the ability to genetically modify these viruses into increasingly potent and
      tumor-specific vectors is a recent phenomenon. As more is learned about the
      functions of viral gene products in controlling the mammalian cell cycle and in
      disabling cellular defense mechanisms, specific viral functions can be augmented
      or eliminated to enhance antineoplastic efficacy. In this article, general
      mechanisms by which oncolytic viruses achieve their antitumor efficacy and
      specificity are reviewed. The paradoxical roles of the immune response are
      addressed with respect to oncolytic viral therapy, as it, on one hand, impedes
      the spread of viral infection, and on the other, augments tumor cell destruction
      through the recruitment of T cells "vaccinated" against tumor antigens. The most
      commonly used oncolytic viruses are each reviewed in turn, including
      adenoviruses, herpes simplex viruses, vaccinia viruses, reoviruses, and Newcastle
      disease viruses. Special attention is focused on the unique biology of each of
      these viruses as well as the status of several of these mutants in clinical
      trials.

PMID- 11961195
TI  - The cancer patient and quality of life.
AB  - Over the last decade, clinicians have accepted that while survival and disease
      free survival are critical factors for cancer patients, overall quality-of-life
      is fundamental. This review considers recent developments in the field of quality
      of life, oncological challenges and future directions.

PMID- 11961196
TI  - Comparable efficacy of epoetin alfa for anemic cancer patients receiving platinum
      and nonplatinum-based chemotherapy: a retrospective subanalysis of two large,
      community-based trials.
AB  - BACKGROUND: Data from two large, community-based clinical trials that evaluated
      the efficacy of epoetin alfa in anemic cancer patients receiving chemotherapy
      were retrospectively analyzed to determine if clinical outcomes were different
      depending on whether chemotherapy was platinum- or nonplatinum-based. PATIENTS
      AND METHODS: Patients received epoetin alfa 150-300 IU/kg (Glaspy: Study 1; n =
      2,342) or 10,000-20,000 IU (Demetri: Study 2; n = 2,370) s.c. three times each
      week for 4 months. Efficacy end points were changes in transfusion requirements,
      hemoglobin (Hb) levels, and quality of life (QOL). A total of 4,298 out of 4,712
      patients (platinum-based, n = 1,601; nonplatinum-based, n = 2,697), who both
      received chemotherapy and had available data, were eligible for this
      retrospective analysis. RESULTS: Baseline characteristics across groups were
      comparable with few exceptions, which were anticipated in view of the
      characteristics of the two different chemotherapy types. Decreases in transfusion
      requirements after 2, 3, and 4 months were significant, regardless of
      chemotherapy type. Mean increases in Hb level from baseline to final evaluation
      ranged from 1.6 g/dl to 2.0 g/dl across study groups and were significant,
      regardless of chemotherapy type. QOL, as measured by the Linear Analog Scale
      Assessment (LASA), improved significantly by 20%-43%, regardless of chemotherapy
      type, and improvements were associated with increases in Hb. Epoetin alfa was
      well tolerated in both studies, regardless of chemotherapy type. CONCLUSION:
      Treatment of anemic cancer patients with epoetin alfa results in significant
      reduction in transfusion requirements, increase in Hb levels, and improvements in
      QOL, regardless of whether the chemotherapy is platinum- or nonplatinum-based.

PMID- 11961197
TI  - The effect of nonmalignant systemic disease on tolerance to radiation therapy.
AB  - PURPOSE: Some patients with nonmalignant systemic diseases, like collagen
      vascular disease (CVD), hypertension, diabetes mellitus, and inflammatory bowel
      disease (IBD), tolerate radiation therapy poorly. Although the mechanisms of each
      of these disease processes are different, they share a common microvessel
      pathology that is potentially exacerbated by radiotherapy. This article reviews
      and evaluates available data examining the effects of these benign disease
      processes on radiation tolerance. METHODS: We conducted a thorough review of the
      Anglo-American medical literature from 1960 to 2001 on the effects of
      radiotherapy on CVD, hypertension, diabetes mellitus, and IBD. RESULTS: Fifteen
      studies were identified that examined the effects of radiation therapy for cancer
      in patients with CVDs. Thirteen of 15 studies documented greater occurrences of
      acute and late toxicities (range 7%-100%). Higher rates of complications were
      noted especially for nonrheumatoid arthritis CVDs. Nine studies evaluated the
      effects of hypertension and diabetes on radiation tolerance. All nine studies
      documented higher rates of late toxicities than in a "control" group (range 34%
      100%). When patients had both diabetes and hypertension, the risk of late
      toxicities was even higher. Six studies examined radiation tolerance of patients
      with IBD irradiated to the abdomen and pelvis. Five of these six studies showed
      greater occurrences of acute and late toxicities for patients with IBD, even with
      precautionary measures like reduced fraction size and volume and patient
      immobilization (13%-29%). CONCLUSION: The majority of published studies
      documented lower radiation tolerance for patients who have CVD, diabetes
      mellitus, hypertension, and IBD. This may reflect a publication bias, as the
      majority of these studies are retrospective with small numbers of patients and
      use different scoring scales for complications. These factors may contribute to
      an overestimation of true radiation-induced morbidity. Although the paucity of
      data makes precise estimates difficult, a subset of patients, in particular,
      those with active CVD, IBD, or a combination of uncontrolled hypertension with
      type I diabetes, is likely to be at higher risk. Future prospective trials need
      to document these disease entities when reporting treatment-related complications
      and also must monitor toxicities associated with quiescent versus active IBD and
      CVD, type I versus type II diabetes, and levels of hypertension (controlled
      versus uncontrolled) matched for radiation-specific treatment sites, field size,
      fractionation, and total dose.

PMID- 11961198
TI  - Osteogenic sarcoma presenting with lung metastasis.
AB  - A patient with osteogenic sarcoma presenting with lung metastases is discussed
      with attention to appropriate diagnosis, staging, and treatment. Multimodality
      treatment options using chemotherapy, orthopedic surgery and thoracic surgery are
      presented. Physical medicine and rehabilitation evaluation and treatment are
      included. Current research options are discussed.

PMID- 11961199
TI  - Between parent and child: negotiating cancer treatment in adolescents.
AB  - Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at
      Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The
      Schwartz Center is a non-profit organization dedicated to supporting and
      advancing compassionate health care delivery, which provides hope to the patient,
      support to caregivers, and sustenance to the healing process. The center sponsors
      the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers
      reflect on important psychosocial issues faced by patients, their families, and
      their caregivers, and gain insight and support from fellow staff members. Cancer
      in adolescents presents an extra dynamic of psychosocial complexity. The case of
      a 19-year-old woman with acute myelocytic leukemia is discussed. Her disease was
      refractory to allogeneic transplantation, and she died with severe graft-versus
      host disease. Ms. P and her mother established very different relationships with
      the team which supported them through the transitions in her care, and Ms. P was
      able to die at home, with hospice care. The personal connection with the team
      enabled a degree of positive adjustment through the nightmare of loss. The
      epidemiology of cancer in adolescents and paradigms of care are reviewed.
      Psychosocial aspects of adolescence, opportunities for personal growth and
      support, and the challenge of end-of-life care are discussed.

PMID- 11961200
TI  - The molecular perspective: tamoxifen and the estrogen receptor.

PMID- 11961204
TI  - Advances in the management of acute promyelocytic leukemia and other hematologic
      malignancies with arsenic trioxide.
AB  - Acute promyelocytic leukemia (APL), once considered the most devastating subtype
      of acute myeloid leukemia, is now the most treatable of all subtypes as a result
      of intensive research into its molecular pathogenesis. This research has led to a
      rational approach to treatment in which the use of the differentiating agent all
      trans-retinoic acid (ATRA) has proven to be effective first-line treatment for
      inducing complete remission. Arsenic trioxide (ATO) is currently used to treat
      relapsed disease, further enhancing survival rates in a patient population for
      which limited salvage options exist. This review discusses the molecular
      mechanisms responsible for development of APL and the evolution of treatment
      options over the last three decades, including the major advances using ATRA and
      ATO in the last 12 years. The mechanism of action of ATO is also described in
      view of this agent's potential for broader therapeutic application in a variety
      of hematologic malignancies.

PMID- 11961205
TI  - Molecular targets of arsenic trioxide in malignant cells.
AB  - Arsenic trioxide (As2O3; ATO) has considerable efficacy in the treatment of
      relapsed acute promyelocytic leukemia (APL), inducing partial differentiation and
      promoting apoptosis of malignant promyelocytes. Although initial studies focused
      on the role of the characteristic APL fusion protein, PML-RARalpha, in mediating
      response to ATO, subsequent investigations have revealed that ATO acts on
      numerous intracellular targets. ATO broadly affects signal transduction pathways
      and causes a wide range of alterations leading to apoptosis. Key mediators of
      sensitivity to ATO-induced apoptosis include intracellular glutathione and
      hydrogen peroxide (H2O2). The loss of inner mitochondrial membrane potential is
      also an important step in ATO-mediated cell killing. Cellular and physiologic
      pathways affected by ATO provide some clues as to the mechanisms for the biologic
      effects of ATO. Recent research has shown that hematologic cancers other than APL
      and solid tumors derived from several tissue types may be responsive to
      monotherapy or combination therapy with ATO. A better understanding of the
      mechanisms of action of ATO may help guide the use of ATO for the treatment of a
      wide variety of malignancies and allow its potential in cancer therapy to be
      fully realized.

PMID- 11961206
TI  - Nontraditional cytotoxic therapies for relapsed/refractory multiple myeloma.
AB  - Multiple myeloma remains an incurable disease, with median survival rates of 4-6
      years even with aggressive, high-dose chemotherapy, bone marrow transplantation,
      and intensive supportive care. Additionally, multiple myeloma is primarily a
      disease of the elderly, many of whom cannot tolerate aggressive chemotherapy.
      Thus, newer treatments with good safety profiles are needed to improve the
      quality of responses and, hopefully, to translate into prolonged progression and
      overall survival. The pathophysiology of multiple myeloma is complex, involving
      many pathways and interactions among cytokines, adhesion molecules, angiogenesis,
      and mechanisms of resistance, which, taken together, provide multiple targets for
      novel therapeutic modalities. Agents currently under investigation for treating
      multiple myeloma include thalidomide and its successors, PS-341, and arsenic
      trioxide. Thalidomide and immunomodulatory drugs both exhibit activity against
      multiple myeloma by affecting different levels of the immune system. PS-341 is a
      proteasome inhibitor that halts the cell cycle, resulting in apoptosis; it also
      inhibits a key transcription factor and may have antiangiogenic activity. Arsenic
      trioxide activates multicellular mechanisms to induce apoptosis, inhibit
      angiogenesis, and stimulate immune responses. Preclinical and early clinical data
      suggest that combination regimens should be pursued, given the different
      mechanisms of action of these compounds on the immune system and their non
      overlapping toxicities at low dosages.

PMID- 11961207
TI  - Multifaceted approach to the treatment of bcr-abl-positive leukemias.
AB  - Bcr-Abl-positive leukemias include chronic myelogenous leukemia (CML), both
      myeloid and lymphoid blast-phase CML, and some cases of acute lymphoblastic
      leukemia. The chimeric bcr-abl gene codes for a tyrosine kinase that is
      constitutively activated in the leukemic cells and plays the central role in
      leukemogenesis. Hematologic malignancies, including Bcr-Abl-positive leukemias,
      also frequently have overactivity of the Ras signaling pathway, leading to
      abnormal transduction of growth and survival signals. New and investigational
      therapeutic options that target these specific molecular defects of leukemic
      cells include the tyrosine kinase inhibitor imatinib mesylate (STI571) and
      farnesyltransferase inhibitors (R115777, SCH66336), which block localization of
      Ras proteins to the cell membrane. While single-agent therapy with these new
      agents may produce hematologic and cytogenetic remissions in patients with Bcr
      Abl-positive leukemias, molecular remissions are less common, and resistance may
      develop. Therefore, the development of a multifaceted therapeutic approach to
      these leukemias is of great interest. Arsenic trioxide (ATO), which has
      significant activity in patients with relapsed and refractory acute promyelocytic
      leukemia, is a potential addition to the therapeutic arsenal. While some of the
      molecular activities of ATO are specific to acute promyelocytic leukemia,
      arsenicals also have a broad variety of antineoplastic properties that may be
      useful in combination therapy with agents that target specific molecular defects
      of Bcr-Abl-positive leukemias.

PMID- 11961208
TI  - New approaches to the treatment of myelodysplasia.
AB  - The therapeutic dilemma that confronts the management of patients with
      myelodysplastic syndromes (MDS) is illustrated by the absence of a Food and Drug
      Administration-approved agent with an indication for this disease. Clinical
      heterogeneity and inadequate understanding of the disease pathobiology have
      limited progress in the development of novel therapeutics. Preclinical
      investigations indicate that reciprocal interaction between the malignant clone
      and the microenvironment serve to create a hostile milieu that reinforces
      ineffective blood cell production. Ineffective hematopoiesis, the hallmark of
      MDS, arises from impaired progenitor responsiveness to normal trophic signals and
      excess local generation of inhibitory cytokines, which promote accelerated
      apoptotic loss of progenitors and their progeny. Evidence to support this model
      derives from cytokine neutralization studies and the direct relationship between
      plasma tumor necrosis factor-alpha concentration and DNA oxidation and
      glutathione depletion in malignant CD34+ progenitors. Recent investigations
      indicate that angiogenic molecules generated by malignant myelomonocytic
      precursors represent integral diffusable signals that reinforce leukemia
      progenitor self-renewal while promoting the generation of proapoptotic cytokines
      and medullary angiogenic response. The potential for leukemia evolution is
      compounded by epigenetic events including methylation silencing of the p15 proto
      oncogene or activating ras point mutations. Delineation of such biologic features
      that are central to the pathobiology of MDS provides a reliable framework for the
      development of novel therapeutics. Antiangiogenic agents in clinical testing
      include vascular endothelial growth factor (VEGF) receptor tyrosine kinase
      inhibitors, thalidomide and related analogues, and the recombinant VEGF
      neutralizing antibody, bevacizumab. Agents whose actions may restore
      differentiation programs, such as the DNA methyltransferase inhibitors or histone
      deacetylase inhibitors, offer the prospect to promote effective hematopoiesis
      while impacting the potential for leukemia evolution. RAS farnesyl transferase
      inhibitors have shown encouraging preliminary results in acute myeloid leukemia
      and are currently under investigation in advanced MDS and chronic myelomonocytic
      leukemia. Arsenic trioxide (ATO) interacts with a spectrum of biologic targets
      that may be uniquely suited to MDS. ATO is a potent inducer of apoptosis in thiol
      depleted malignant progenitors and neovascular endothelium, while promoting
      differentiation through histone acetylation and inactivation of transcriptional
      corepressors. The identification of relevant biologic targets in MDS has raised
      expectations for the development of disease-specific therapies for MDS in the
      years that follow.

PMID- 11961209
TI  - Choline deficiency associated with diethanolamine carcinogenicity.

PMID- 11961210
TI  - Environmental stress mediates changes in neuroimmunological interactions.
AB  - Combinations of environmental stress coordinately increase toxicological assaults
      on health, dependent on the genetics of the exposed organism. Multiple gene
      variances between individuals influence the risks associated with environmental
      exposures, and environmental stress presents in multiple forms including
      chemical, physical, and psychological stresses. Combined chemical, physical, and
      psychological stresses are suggested as exacerbating the initiation and/or
      duration of illnesses, and many of the detrimental outcomes on health are posited
      to relate to changes in neuroendocrine immune circuitry. However, most human
      epidemiological or experimental animal studies have not considered the
      combination of chemical, physical, and psychological stress on health status.
      Current consideration is being given to "real world" exposures for assessment of
      health risk, but this mainly relates to evaluation of chemical mixtures. In
      addition to concomitant chemical exposures having agonistic and/or antagonistic
      interactions, the physical and psychological status of the individual can
      influence exposure outcomes. An individual's psychosocial environment is likely
      to be important in epidemiological investigations. Neuroimmunology is a
      burgeoning discipline, and neurotoxicology and immunotoxicology studies should
      consider the bidirectional regulatory mechanisms between these organ systems and
      the potential long-term influences of psychological stress. This mini-review
      discusses some intriguing data from animal and human studies, which address the
      regulatory pathways between the neural, endocrine, and immune systems, with
      emphasis on psychological stress.

PMID- 11961211
TI  - Epigenetics and DNA methylation come of age in toxicology.
AB  - A wide variety of chemical and physical agents have the potential to produce
      adverse effects by causing heritable changes to the genome, resulting in
      heritable alterations in phenotype. These are often assumed to be a consequence
      of mutation. However, mutagenesis is not the only mechanism underlying heritable
      alterations to the genome. It is important to understand that there may also be
      an epigenetic basis for this. DNA methylation is the epigenetic mechanism that
      this review focuses upon. We indicate how altered methylation may play a key role
      in a variety of chemical-induced toxicities, including, but not limited to,
      carcinogenesis, and we point out how an assessment of methylation status can
      provide important information as a component of an overall safety assessment.

PMID- 11961212
TI  - PBPK modeling of the percutaneous absorption of perchloroethylene from a soil
      matrix in rats and humans.
AB  - Perchloroethylene (PCE) is a widely used volatile organic chemical. Exposures to
      PCE are primarily through inhalation and dermal contact. The dermal absorption of
      PCE from a soil matrix was compared in rats and humans using real-time MS/MS
      exhaled breath technology and physiologically based pharmacokinetic (PBPK)
      modeling. Studies with rats were performed to compare the effects of loading
      volume, concentration, and occlusion. In rats, the percutaneous permeability
      coefficient (K(P)) for PCE was 0.102 +/- 0.017, and was independent of loading
      volume, concentration, or occlusion. Exhaled breath concentrations peaked within
      1 h in nonoccluded exposures, but were maintained over the 5 h exposure period
      when the system was occluded. Three human volunteers submerged a hand in a
      container of PCE-laden soil for 2 h and their exhaled breath was continually
      monitored during and for 2.5 h following exposure. The absorption and elimination
      kinetics of PCE were slower in these subjects than initially predicted based upon
      the PBPK model developed from rat dermal kinetic data. The resulting K(P) for
      humans was over 100-fold lower than for the rat utilizing a single, well-stirred
      dermal compartment. Therefore, two additional PBPK skin compartment models were
      evaluated: a parallel model to simulate follicular uptake and a layered model to
      portray a stratum corneum barrier. The parallel dual dermal compartment model was
      not capable of describing the exhaled breath kinetics, whereas the layered model
      substantially improved the fit of the model to the complex kinetics of dermal
      absorption through the hand. In real-world situations, percutaneous absorption of
      PCE is likely to be minimal.

PMID- 11961213
TI  - In vitro bioavailability of heavy metals in pressure-treated wood dust.
AB  - Pressure treatment with chromium, copper, and arsenic (CCA) is the most prevalent
      method for protecting wood used in outdoor construction projects. Although these
      metals are tightly bound to the wood fibers and are not released under most
      conditions of use, we examined the bioavailability of metals in CCA pressure
      treated wood dust in vitro. Cytotoxicity and metallothionein (MT) mRNA expression
      were examined in V79 Chinese hamster lung fibroblast cells incubated with
      respirable-size wood dust generated by sanding CCA-treated and untreated
      (control) Southern yellow pine. In colony survival studies, increased
      cytotoxicity (p < 0.05) occurred in V79 cells treated with CCA wood dust (351 +/-
      77 microg/ml, mean +/- SE) compared with control wood dust (883 +/- 91
      microg/ml). Increased cytotoxicity with CCA wood dust also occurred in an arsenic
      resistant subline of V79 cells, thus suggesting that arsenic was not responsible
      for the increased cytotoxicity. Metallothionein mRNA was significantly increased
      after 48 h of treatment with CCA wood dust compared with control wood dust.
      Incubation of CCA wood dust in cell culture media resulted in the transfer of
      copper, but not chromium or arsenic, into the media. Moreover, the treatment of
      cells with this filtered extract resulted in significantly increased
      metallothionein mRNA, suggesting that bioavailable copper is responsible for
      inducing metallothionein mRNA in V79 cells. Thus, these bioassays suggest that
      metals become bioavailable during in vitro culture of phagocytic V79 cells with
      CCA wood dust.

PMID- 11961215
TI  - Associations between weight loss-induced changes in plasma organochlorine
      concentrations, serum T(3) concentration, and resting metabolic rate.
AB  - Organochlorine compounds are released from body fat into the bloodstream during
      weight loss. Because these compounds may impair thyroid status, which is
      implicated in the control of resting metabolic rate (RMR), the aim of this study
      was to determine if the augmentation in plasma organochlorine concentrations
      might be associated with the decrease in serum T(3) concentration and RMR
      observed in response to body weight loss. Plasma organochlorine concentrations,
      serum T(3) concentration, and RMR were measured before and after weight loss in
      16 obese men who followed a nonmacronutrient-specific energy-restricted diet for
      15 weeks. As expected, a significant decrease in serum T(3) concentration and RMR
      was observed after the program, whereas concentrations of most detected
      organochlorines were significantly increased. Changes in organochlorine
      concentrations were negatively associated with changes in serum T(3)
      concentration (significantly for p,p'-DDT, HCB, Aroclor 1260, PCB 28, PCB 99, PCB
      118, and PCB 170) and with changes in RMR adjusted for weight loss (significantly
      for HCB and PCB 156). In conclusion, organochlorines released in plasma during
      weight loss are associated with the documented decrease in serum T(3)
      concentration and RMR. Further studies are needed to verify whether these
      findings are causally related.

PMID- 11961214
TI  - Diethanolamine induces hepatic choline deficiency in mice.
AB  - The purpose of the present experiments was to test the hypothesis that
      diethanolamine (DEA), an alkanolamine shown to be hepatocarcinogenic in mice,
      induces hepatic choline deficiency and to determine whether altered choline
      homeostasis was causally related to the carcinogenic outcome. To examine this
      hypothesis, the biochemical and histopathological changes in male B6C3F1 mice
      made choline deficient by dietary deprivation were first determined.
      Phosphocholine (PCho), the intracellular storage form of choline was severely
      depleted, decreasing to about 20% of control values with 2 weeks of dietary
      choline deficiency. Other metabolites, including choline, glycerophosphocholine
      (GPC), and phosphatidylcholine (PC) also decreased. Hepatic concentrations of S
      adenosylmethionine (SAM) decreased, whereas levels of S-adenosylhomocysteine
      (SAH) increased. Despite these biochemical changes, fatty liver, which is often
      associated with choline deficiency, was not observed in the mice. The dose
      response, reversibility, and strain-dependence of the effects of DEA on choline
      metabolites were studied. B6C3F1 mice were dosed dermally with DEA (0, 10, 20,
      40, 80, and 160 mg/kg) for 4 weeks (5 days/week). Control animals received either
      no treatment or dermal application of 95% ethanol (1.8 ml/kg). PCho was most
      sensitive to DEA treatment, decreasing at dosages of 20 mg/kg and higher and
      reaching a maximum 50% depletion at 160 mg/kg/day. GPC, choline, and PC also
      decreased in a dose-dependent manner. At 80 and 160 mg/kg/day, SAM levels
      decreased while SAH levels increased in liver. A no-observed effect level (NOEL)
      for DEA-induced changes in choline homeostasis was 10 mg/kg/day. Choline
      metabolites, SAM and SAH returned to control levels in mice dosed at 160 mg/kg
      for 4 weeks and allowed a 2-week recovery period prior to necropsy. In a manner
      similar to dietary choline deficiency, no fatty change was observed in the liver
      of DEA-treated mice. In C57BL/6 mice, DEA treatment (160 mg/kg) also decreased
      PCho concentrations, without affecting hepatic SAM levels, suggesting that strain
      specific differences in intracellular methyl group regulation may influence
      carcinogenic outcome with DEA treatment. Finally, in addition to the direct
      effects of DEA on choline homeostasis, dermal application of 95% ethanol for 4
      weeks decreased hepatic betaine levels, suggesting that the use of ethanol as a
      vehicle for dermal application of DEA may exacerbate or confound the biochemical
      actions of DEA alone. Collectively, the results demonstrate that DEA treatment
      causes a spectrum of biochemical changes consistent with choline deficiency in
      mice and demonstrate a clear dose concordance between DEA-induced choline
      deficiency and hepatocarcinogenic outcome.

PMID- 11961216
TI  - Evaluation of the 20-day pubertal female assay in Sprague-Dawley rats treated
      with DES, tamoxifen, testosterone, and flutamide.
AB  - The Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC) has
      recommended the rodent pubertal female assay as a Tier I test to detect potential
      endocrine disrupters (EDs). This assay is designed to screen estrogenic activity
      in immature rats exposed to chemicals during sexual maturation. The aim of this
      study was to evaluate whether this assay can detect the EDs with effects brought
      about through various mechanisms. Immature Sprague-Dawley female rats (21 days of
      age) were dosed daily for 20 days by oral gavage (DES, tamoxifen, and flutamide)
      or sc injection (testosterone). The mean age at vaginal opening (VO) was 32.3 +/-
      0.5 days in control rats. Although VO was unaffected by DES at doses of 0.2 and
      1.0 microg/kg, a high dose of DES (5.0 microg/kg) significantly advanced the age
      at VO to 24 days. Both tamoxifen (50 and 200 microg/kg) and flutamide (25 mg/kg)
      also significantly accelerated VO to 27.8 +/- 0.5, 25.1 +/- 0.1, and 26.1 +/-
      0.1, respectively. However, testosterone dose-dependently delayed VO (exposure to
      1.0 mg/kg extended VO to 37.3 +/- 0.8 days, and VO did not occur in 2 of 10
      animals by the time of necropsy at 41 days of age). Estrous cyclicity was
      monitored in rats from VO to necropsy. Irregular cycles were observed in the
      groups treated with DES (5.0 microg/kg), tamoxifen (200 microg/kg), testosterone
      (1.0 mg/kg), and flutamide (25 mg/kg). High dose of DES showed a persistent
      estrus state throughout the entire observation period. In addition, the number of
      days in diestrus was increased by tamoxifen (200 microg/kg) and flutamide (25
      mg/kg) treatments. Significant decreases in ovarian weight were observed in 5.0
      microg/kg DES (64% of control), 25 mg/kg flutamide (76% of control), and 200
      microg/kg tamoxifen (47% of control). Testosterone also significantly decreased
      the ovarian weights in all treatment groups. Uterine weights were also decreased
      significantly at high doses of tamoxifen (200 microg/kg, 39% of control) or
      testosterone (1.0 mg/kg, 47% of control). In hormone analysis, tamoxifen
      significantly increased serum E(2) levels at 50 microg/kg. The mean serum levels
      of TSH were significantly increased in tamoxifen (10 and 50 microg/kg),
      testosterone (0.2 mg/kg), and flutamide (1.0 and 25 mg/kg) treatment groups
      compared with the control. However, serum T(4) levels were significantly reduced
      by testosterone. Furthermore, serum T(3) levels were significantly increased in
      DES, tamoxifen (10 and 50 microg/kg), testosterone (1.0 mg/kg), and flutamide
      (1.0 and 5 mg/kg). Our data demonstrate that the rodent pubertal female assay is
      useful for identifying potential EDs having not only estrogenic/antiestrogenic
      but also androgenic/antiandrogenic activities. However, further validation study
      is necessary to identify chemicals that operate through other action mechanisms,
      including steroid biosynthesis inhibitors and thyroid inhibitors. Moreover,
      additional data on other compounds with weak endocrine disrupting activity will
      be required to further characterize the sensitivity of the female pubertal assay.

PMID- 11961217
TI  - Persistent abnormalities in the rat mammary gland following gestational and
      lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure during gestation has revealed
      reproductive anomalies in rat offspring, including inconclusive reports of
      stunted mammary development in females (Brown et al., 1998, Carcinogenesis 19,
      1623-1629; Lewis et al., 2001, TOXICOL: Sci. 62, 46-53). The current studies were
      designed to examine mammary-gland development in female offspring exposed in
      utero and lactationally to TCDD, and to determine a critical exposure period and
      cellular source of these effects. Long-Evans rats were exposed to 1 microg
      TCDD/kg body weight (bw) or vehicle on gestation day (GD) 15. TCDD-exposed
      females sacrificed on postnatal days (PND) 4, 25, 33, 37, 45, and 68 weighed
      significantly less than control litter mates, and peripubertal animals exhibited
      delayed vaginal opening and persistent vaginal threads, yet did not display
      altered estrous cyclicity. Mammary glands taken from TCDD-exposed animals on PND
      4 demonstrated reduced primary branches, decreased epithelial elongation, and
      significantly fewer alveolar buds and lateral branches. This phenomenon persisted
      through PND 68 when, unlike fully developed glands of controls, TCDD-exposed rats
      retained undifferentiated terminal structures. Glands of offspring exposed to
      TCDD or oil on gestation days 15 and 20 or lactation days 1, 3, 5, and 10 were
      examined on PND 4 or 25 to discern that GD 15 was a critical period for
      consistent inhibition of epithelial development. Experiments using mammary
      epithelial transplantation between control and TCDD-exposed females suggested
      that the stroma plays a major role in the retarded development of the mammary
      gland following TCDD exposure. Our data suggest that exposure to TCDD prior to
      migration of the mammary bud into the fat pad permanently alters mammary
      epithelial development in female rat offspring.

PMID- 11961218
TI  - Effects of primary exposure to environmental and natural estrogens on
      vitellogenin production in carp (Cyprinus carpio) hepatocytes.
AB  - Vitellogenin (vtg) is a precursor of the yolk proteins lipovitelline and
      phosvitin and is synthesized as a consequence of estrogen-dependent gene
      expression in female and male hepatocytes of egg-laying vertebrates. Freshly
      isolated carp hepatocytes of a genetically uniform strain of adult male carp
      (Cyprinus carpio) were used to investigate the effects of primary exposure to
      estrogenic compounds on the vitellogenic response to xenoestrogens. Isolated carp
      hepatocytes were first exposed (primary exposure) to 50 or 100 microM of either
      methoxychlor (MXCL) or bisphenol A (BPA), different concentrations of estrone
      (E1; 1 or 10 nM) or 17beta-estradiol (E2; 0.1 or 1 nM) for 2 days. Hepatocytes
      were exposed to xenoestrogens (secondary exposure) at both 2 and 5 days after
      isolation. Hepatocytes were cultured for a total period of 8 days. A competitive
      indirect ELISA was used to determine the level of vtg after 8 days. The
      concentration of chemicals used for the primary exposure induced vtg to a level
      that was less than 10% of the response elicited by E2 (1000 nM). A cytotoxic
      response, measured by MTT, was not observed after primary exposure to any of the
      xenoestrogens. After primary exposure to MXCL, vtg production in response to E2
      was increased by 4-fold, and vitellogenesis in response to E1 treatment was
      doubled compared with vitellogenesis without pretreatment. No significant
      differences were observed between primary exposure to 50 and 100 microM MXCL.
      Primary exposure to 50 and 100 microM BPA increased the maximum vtg production in
      response to secondary E2 exposure by about 5- and 7-fold, respectively. Primary
      exposure to BPA (50 and 100 microM) followed by secondary exposure to E1 showed a
      4- and 5-fold increase of the vtg synthesis in comparison to E1 exposure alone.
      Primary exposure to the endogenous estrogens had no significant influence on the
      vtg synthesis in response to secondary exposure to E1 or E2. Compared to
      hepatocytes exposed only to MXCL or BPA, primary exposure to E2 increased the vtg
      synthesis in hepatocytes induced by MXCL or BPA by almost a factor of 2. Primary
      exposure to E1 increased vitellogenesis after secondary exposure to MXCL only
      marginally. The present results indicate that weakly estrogenic environmental
      chemicals such as MXCL and BPA can increase the sensitivity of carp hepatocytes
      towards endogenous estrogens with respect to VTG synthesis.

PMID- 11961219
TI  - In vitro hepatotoxicity of the cyanobacterial alkaloid cylindrospermopsin and
      related synthetic analogues.
AB  - Cylindrospermopsin (CY), a sulfate ester of a tricyclic guanidine substituted
      with a hydroxymethyluracil, is a cyanobacterial toxin of increasing environmental
      import as it frequently occurs in drinking water reservoirs. As a toxin, CY
      mainly targets the liver but also involves other organs. In hepatocytes CY
      inhibits the synthesis of protein and of glutathione, leading to cell death. The
      total chemical synthesis of CY has recently been reported (Xie et al., 2000, J.
      Am. Chem. Soc. 22, 5017-5024). The synthesis has provided analogues of CY to
      study aspects of the relationship between chemical structure and activity that
      contribute to toxicity. Protein synthesis inhibition was measured in vitro using
      a rabbit reticulocyte system. Primary cultures of rat hepatocytes were used to
      determine the biological activity of CY and analogues in intact cells. Protein
      synthesis and cell glutathione levels were measured. We could distinguish between
      CY transport and biological activity by comparing the results in vitro to those
      in intact cells. The role of the sulfate group in CY toxicity was examined by
      comparing biological effects of CY with that of CY-DIOL (synthetic CY lacking the
      sulfate group). The sulfate group was found not to play a role in CY activity or
      in its uptake into cells, since there was no significant difference in biological
      activity in vitro or in cells between natural CY and CY-DIOL. The orientation of
      the hydroxyl group at C7 also had no impact on biological activity or transport
      of CY, since the C7 epimer of CY (EPI-CY) and the corresponding diol (EPI-DIOL)
      had activity similar to RAC-CY in vitro and in intact cells. AB-MODEL, the
      analogue lacking an intact C ring, and the methyl and hydroxyl groups of ring A
      could inhibit protein synthesis (but at concentrations 500-1000-fold higher than
      natural CY). Other structurally simpler synthetic analogues lacked biological
      activity.

PMID- 11961220
TI  - Proinflammatory and Th1 cytokine alterations following ultraviolet radiation
      enhancement of disease due to influenza infection in mice.
AB  - Exposure of rodents to immunosuppressive agents such as ozone, dioxin, or
      ultraviolet radiation (UVR) leads to increased morbidity and mortality following
      influenza virus infection. However, these adverse effects are not related to the
      suppression of virus-specific immune responses. Our laboratory showed that UVR
      increased the morbidity, mortality, and pathogenesis of influenza virus without
      affecting protective immunity to the virus, as measured by resistance to
      reinfection, suggesting that UVR and other immunosuppressive pollutants such as
      dioxin and ozone may exacerbate early responses that contribute to the
      pathogenesis of a primary viral infection. In the present study, we examined the
      mechanism of UVR-enhanced mortality in the absence of effects on virus-specific
      immunity and tested the hypothesis that modulation of cytokine levels was
      associated with increased deaths and body weight loss. BALB/c mice were exposed
      to 8.2 kJ/m(2) UVR and were infected 3 days later with a sublethal influenza
      virus infection (LD(40) of mouse-adapted Hong Kong influenza A/68, H(3)N(2)).
      Influx of inflammatory cells, proinflammatory cytokines, and cytokines produced
      by T-helper lymphocytes (Th1 and Th2) were measured in lung homogenates (LH) as
      well as in bronchoalveolar lavage fluid (BAL). UVR preexposure decreased the
      influenza-induced lymphocytic influx 5 days after infection, but did not alter
      macrophage and neutrophil influx into the lung, or increase virus titers
      significantly. Although interferon (IFN)-gamma, total interleukin (IL)-12, IL-6,
      and TNF-alpha were altered in mice that received UVR exposure prior to infection,
      no clear association was made that correlated with the UVR-induced increase in
      body weight loss and mortality due to influenza infection.

PMID- 11961222
TI  - Neonatal exposure to the brominated flame retardant 2,2',4,4',5
      pentabromodiphenyl ether causes altered susceptibility in the cholinergic
      transmitter system in the adult mouse.
AB  - Polybrominated diphenyl ethers (PBDEs) are used as flame-retardants and have
      recently been shown to be increasing in the environment and in human mother's
      milk. We have recently reported that neonatal exposure to 2,2',4,4',5-pentaBDE
      (PBDE 99) can induce persistent aberrations in spontaneous behavior and also
      affect learning and memory functions in the adult animal. The present study
      indicates that the cholinergic system, in its developing stage, may be a target
      of and sensitive to PBDEs. Neonatal exposure of male NMRI mice on postnatal day
      10, to 2,2',4,4',5-pentaBDE (8 mg/kg bw) was shown to alter the response to a
      cholinergic agent, nicotine, at an adult age. The nicotine-induced behavior test
      revealed a hypoactive response to nicotine in PBDE 99-treated animals, whereas
      the response of controls was an increased activity. These findings show
      similarities to observations made from neonatal exposure to PCBs and nicotine,
      compounds shown to affect cholinergic nicotinic receptors. This indicates that
      PBDE 99 can affect the cholinergic system and might thereby interact with other
      environmental toxicants.

PMID- 11961221
TI  - A brominated flame retardant, 2,2',4,4',5-pentabromodiphenyl ether: uptake,
      retention, and induction of neurobehavioral alterations in mice during a critical
      phase of neonatal brain development.
AB  - Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame
      retardant additives. In a recent study, we have seen that neonatal exposure to
      some brominated flame retardants can cause permanent aberrations in spontaneous
      motor behavior that seem to worsen with age. In view of an increasing amount of
      PBDEs in mother's milk and in the environment, the present study was undertaken
      to investigate whether there is a critical and limited phase, during neonatal
      life, for induction of persistent neurotoxic effects of 2,2',4,4',5-pentaBDE
      (PBDE 99). Neonatal NMRI male mice were exposed on day 3, 10, or 19 to 8 mg
      2,2',4,4',5-pentaBDE/kg body weight. Uptake and retention of 2,2',4,4',5
      penta[(14)C]BDE were studied in the mouse brain after exposure to 1.5 M becquerel
      (Bq) 2,2',4,4',5-penta[(14)C]BDE /kg body weight (bw) on postnatal day 3, 10, or
      19. Spontaneous motor behavior was observed in 4-month-old mice. Mice exposed to
      2,2',4,4',5-pentaBDE on day 3 or 10 showed significantly impaired spontaneous
      motor behavior, whereas no effect was seen in mice exposed on day 19. Neonatal
      mice exposed to 2,2',4,4',5-penta[(14)C]BDE 99 on postnatal day 3, 10, or 19 were
      sacrificed 24 h or 7 days posttreatment. The amount of radioactivity, given as
      per mille ( per thousand) of total amount administered, was between 3.7 and 5.1
      per thousand in the three different age categories at 24 h after administration.
      Seven days after the administration, 2,2',4,4',5-penta[(14)C]BDE or its
      metabolites could still be detected in the brain. The amount of radioactivity in
      the brain was not higher in mice exposed on day 3 or 10 when compared to exposure
      on day 19. Thus, the behavioral disturbances observed in adult mice following
      neonatal exposure to 2,2',4,4',5-pentaBDE are induced during a defined critical
      period of neonatal brain development.

PMID- 11961223
TI  - Cadmium-metallothionein interactions in the olfactory pathways of rats and pikes.
AB  - Deposition of cadmium onto the olfactory epithelium results in transport of the
      metal along the primary olfactory neurons to the olfactory bulbs of the brain.
      The present investigation was undertaken to determine the intracellular ligand
      binding of cadmium during this process. (109)Cd(2+) was applied on the olfactory
      epithelium of rats and pikes, and the subcellular distribution of the metal in
      the olfactory pathways was then examined. Two groups of rats were used: one
      pretreated with intranasal instillations of nonlabeled cadmium and the other
      given physiological saline (controls). Cellular fractionations showed that the
      (109)Cd(2+) was predominantly present in the cytosol of all samples, both in the
      rats and the pikes. Gel filtrations of the olfactory epithelium of control rats
      killed 2 h after the (109)Cd(2+) instillation showed that the metal was recovered
      in two peaks with elution volumes corresponding to metallothionein (MT) and
      glutathione (GSH)-the latter peak being the predominant one. However, in the
      epithelium of the cadmium-pretreated rats killed at 2 h, (109)Cd(2+) was
      recovered in one peak corresponding to MT. In the olfactory epithelium and bulbs
      of both groups of rats killed at 48 h, as well as in the olfactory epithelium,
      nerves, and bulbs of pikes killed at this interval, (109)Cd(2+) was recovered in
      one peak corresponding to MT. Immunohistochemistry of the olfactory system of
      rats given cadmium in the right nasal cavity showed induction of MT in the
      neuronal, sustentacular, and basal cells of the right olfactory epithelium, in
      the nerve fascicles in the lamina propria of the right olfactory mucosa, and in
      the olfactory nerve layer of the right olfactory bulb. On the left side, the
      immunoreactivity was low in these structures. MT immunoreactivity was observed in
      the glomeruli of both the right and the left olfactory bulbs. However, the
      staining was homogeneously distributed within the entire glomeruli of the right
      bulb, whereas it showed a mesh-like pattern corresponding to the localization of
      astrocytes in the glomeruli of the left bulb. We conclude that exposure of the
      olfactory epithelium to cadmium results in induction of MT in the primary
      olfactory neurons and a transport of the metal in these neurons as a cadmium
      metallothionein (CdMT) complex. Our results further indicate that GSH is a ligand
      that can interact with cadmium before the metal binds to MT.

PMID- 11961224
TI  - Biochemical changes in the central nervous system of rats exposed to 1
      bromopropane for seven days.
AB  - 1-Bromopropane is used widely as an alternative to ozone-depleting solvents. The
      neurotoxic effects of this agent have been described in humans and experimental
      animals. Here we investigated the underlying mechanisms of the neurotoxic effects
      of 1-bromopropane by examining the initial biochemical changes in the central
      nervous system. Four groups of 9 Wistar male rats each were exposed to 200, 400,
      or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 7 days. At the end
      of the experiment, the cerebrum, cerebellum, brain stem and lumbar enlargement of
      the spinal cord were dissected out from each rat (n = 8) for biochemical
      analyses. Morphological examinations of the nervous system were performed in the
      remaining rat of each group. 1-Bromopropane dose-dependently decreased
      neurospecific gamma-enolase, total glutathione, and nonprotein sulfhydryl groups
      in the cerebrum and cerebellum. Creatine kinase activity decreased dose
      dependently in the brain and spinal cord. Histopathological examination showed
      swelling of preterminal axons in gracile nucleus and degeneration of myelin in
      peripheral nerves. Our results of low levels of gamma-enolase suggested that 1
      bromopropane might primarily cause functional or cellular loss of neurons in the
      cerebrum and cerebellum. Glutathione depletion or modification to functional
      proteins containing a sulfhydryl base as a critical site might be the underlying
      mechanism of 1-bromopropane neurotoxicity.

PMID- 11961225
TI  - Evaluation of the aromatase inhibitor fadrozole in a short-term reproduction
      assay with the fathead minnow (Pimephales promelas).
AB  - Cytochrome P450 aromatase (CYP19) is a key enzyme in vertebrate steroidogenesis,
      catalyzing the conversion of C19 androgens to C18 estrogens such as beta
      estradiol (E2). The objective of this study was to assess effects of the CYP19
      inhibitor fadrozole on fathead minnow (Pimephales promelas) reproductive
      endocrinology and physiology in a short-term reproduction assay proposed for
      identifying specific classes of endocrine-disrupting chemicals. A concentration
      dependent reduction in fecundity was observed in fish exposed for 21 days to
      water concentrations of fadrozole ranging from 2 to 50 microg/l. Consistent with
      the expected mechanism of action, there was a significant inhibition of brain
      aromatase activity in both male and female fathead minnows exposed to fadrozole.
      In females, this inhibition was accompanied by a concentration-dependent decrease
      in plasma E2 and vitellogenin concentrations; the latter observation is
      consistent with the fact that activation of the estrogen receptor by E2 initiates
      hepatic vitellogenin production in oviparous vertebrates. Histological assessment
      of ovaries from females exposed to fadrozole indicated a decrease in mature
      oocytes and an increase in preovulatory atretic follicles. Exposure of male
      fathead minnows to fadrozole significantly increased plasma concentrations of the
      androgens testosterone (T) and 11-ketotestosterone (KT) and resulted in a marked
      accumulation of sperm in the testes. Results of this study indicate that the
      proposed fathead minnow assay should effectively identify test chemicals as
      potential aromatase inhibitors, both in the context of their reproductive
      toxicity and the specific mechanism of action. These results also should be of
      utility in assessing the potential ecological risk of CYP19 inhibitors, in
      particular in the context of relating alterations in subcellular indicators of
      endocrine function (changes in steroids, proteins) to adverse consequences in the
      whole organism.

PMID- 11961226
TI  - Effects of subchronic exposure to a complex mixture of persistent contaminants in
      male rats: systemic, immune, and reproductive effects.
AB  - Human populations throughout the world are exposed daily to low levels of
      environmental contaminants. The consequences of potential interactions of these
      compounds to human endocrine, reproductive, and immune function remain unknown.
      The current study examines the effects of subchronic oral exposure to a complex
      mixture of ubiquitous persistent environmental contaminants that have been
      quantified in human reproductive tissues. The dosing solution used in this study
      contained organochlorines (2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD],
      polychlorinated biphenyls [PCBs],p,p'-dichlorodiphenoxydichloroethylene [p,p'
      DDE],p,p-dichlorodiphenoxytrichloroethane [p,p'-DDT], dieldrin, endosulfan,
      methoxychlor, hexachlorobenzene, and other chlorinated benzenes,
      hexachlorocyclohexane, mirex and heptachlor) as well as metals (lead and
      cadmium). Each chemical was included in the mixture at the minimum risk level
      (MRL) or tolerable daily intake (TDI) as determined by the U.S. EPA or ATSDR or,
      for TCDD, at the no observable effect level (NOEL) used to calculate the TDI.
      Sexually mature male rats were exposed to this complex mixture at 1, 10, 100, and
      1000 times the estimated safe levels daily for 70 days. On day 71, all animals
      were sacrificed and a variety of physiological systems assessed for toxic
      effects. Evidence of hepatotoxicity was seen in the significant enlargement of
      the liver in the 1000x group, reduced serum LDH activity (100x), and increased
      serum cholesterol and protein levels (both 1000x). Hepatic EROD activities were
      elevated in animals exposed to10x and above. The mixture caused decreased
      proliferation of splenic T cells at the highest dose and had a biphasic effect on
      natural killer cell lytic activity with an initial increase in activity at 1x
      followed by a decrease to below control levels in response to 1000x. No treatment
      related effects were seen on bone marrow micronuclei, daily sperm production,
      serum LH, FSH, or prolactin levels or weights of most organs of the reproductive
      tract. The weights of the whole epididymis and of the caput epididymis were
      significantly decreased at 10x and higher doses, although no effect was seen on
      cauda epididymal weight. The sperm content of the cauda epididymis was increased
      at the 1x level but not significantly different from control at higher dose
      levels. A slight, but significant, increase in the relative numbers of spermatids
      was seen in the animals from the 1000x group with a trend towards reduced
      proportion of diploid cells at the same dose. Only minor, nondose related changes
      were seen in parameters related to condensation of chromatin, as determined by
      flow cytometry, in epididymal sperm. We conclude that the mixture induced effects
      on the liver and kidney and on general metabolism at high doses but caused only
      minor effects on immune function, reproductive hormone levels, or general indices
      of reproductive function measures. These data suggest that additive or
      synergistic effects of exposure to contaminants resulting in residue levels
      representative of contemporary human tissue levels are unlikely to result in
      adverse effects on immune function or reproductive physiology in male rats.

PMID- 11961227
TI  - Evaluation of spinosad in a two-generation dietary reproduction study using
      Sprague-Dawley rats.
AB  - Spinosad, an insecticide derived from a naturally occurring bacterium via
      fermentation, represents a new class of insecticides acting by a novel mode of
      action. A dietary study was conducted in Sprague-Dawley rats in which groups of
      30 rats/sex/dosage level were given diets that provided 0, 3, 10, or 100 mg
      spinosad/kg body weight/day, 7 days/week, for 2 successive generations. Following
      10 weeks of dietary exposure, the P1 generation was mated twice to produce F1a
      and F1b litters. After weaning, groups of 30 rats/sex/dosage level were selected
      from the F1a litters, given diets containing spinosad for 12 weeks, and mated to
      produce the F2 generation. Dietary administration of spinosad to rats at a dosage
      of 100 mg/kg/day over 2 generations produced parental toxicity and effects on the
      offspring. Among adult males, body weights and weight gains were decreased 2-9%
      relative to controls, with P1 males more affected than P2. Absolute and relative
      liver, kidney, heart, spleen, and thyroid weights were increased by from 12% to
      as much as 240% of control values. Histologic changes consistent with cationic
      amphiphilic compounds were noted in the kidneys, lungs, mesenteric lymph nodes,
      spleen, and thyroid of P1 and P2 males and females. In females given 100
      mg/kg/day, though premating body weights were not affected, weight gains during
      the F1a and F1b gestation periods were depressed 15-16%. Increased incidences of
      dystocia, and vaginal bleeding and mortality occurred during parturition and
      lactation at 100 mg/kg/day. Effects on the offspring (decreased litter size and
      survival through day 4 of lactation) were limited to the high-dosage group. Signs
      indicative of poor maternal care noted in the pups (stomachs void of milk, cold,
      thin, etc.) were observed at 100 mg/kg/day. Early postnatal effects on the
      offspring were considered likely secondary to the effects in maternal animals
      around the time of parturition. At 100 mg/kg/day, weight gain in pups was
      depressed throughout lactation, with statistically significantly decreased
      weights noted toward the latter half of the lactation period. There were no
      treatment-related effects on adults or their offspring at 3 or 10 mg/kg/day in
      either generation. Based on these results, spinosad is not considered a selective
      reproductive toxicant, (i.e., no effects on reproductive parameters were noted
      below a level that produced toxicity in the adults) and the no observed effect
      level (NOEL) for both parental and reproductive/perinatal toxicity was 10
      mg/kg/day.

PMID- 11961228
TI  - Lung cancer.

PMID- 11961230
TI  - Whatever happened to thrombopoietin?

PMID- 11961231
TI  - The McLeod syndrome: an example of the value of integrating clinical and
      molecular studies.

PMID- 11961232
TI  - Point mutations causing the McLeod phenotype.
AB  - BACKGROUND: The McLeod phenotype is defined by absence of Kx, weakening of Kell
      system antigens, and acanthocytosis. Individuals with the McLeod phenotype
      usually develop late-onset neuromuscular abnormalities. Gene deletions,
      insertions, and point mutations that affect RNA splicing or that lead to
      premature stop codons have been reported to cause the McLeod phenotype. The
      McLeod phenotype may also be caused by mutations at a different splice site and
      by a novel mutation encoding an amino acid substitution that prevents transport
      to the cell surface. STUDY DESIGN AND METHODS: The coding and flanking intron
      regions of XK from four male, unrelated individuals with the McLeod phenotype and
      non-chronic granulomatous disease were sequenced and compared with the wild type
      sequence. Genomic DNA was amplified by PCR, and the products were sequenced. In
      one case, the mutant cDNA was expressed in a heterologous cell, and cell surface
      expression was determined. RESULTS: Three individuals with the McLeod phenotype
      had mutations that disrupted conserved GT sequences present at RNA splice sites.
      Two of them had G>C mutations at the 5' splice site of intron 1, and one had a
      G>A mutation at the 5' splice site of intron 2. One person with the McLeod
      phenotype had a 746C>G mutation in exon 3 encoding an R222G substitution. In a
      transfected cell, the expressed protein from the latter mutant did not travel to
      the cell surface. CONCLUSION: The McLeod phenotype may be caused by several
      different mutations.

PMID- 11961233
TI  - A weak blood group A phenotype caused by a new mutation at the ABO locus.
AB  - BACKGROUND: A number of alleles have been described for ABO encoding for common
      and rare ABO blood group phenotypes. Critical mutations in the coding sequence of
      ABO that may confer the different specificity and activity of the
      glycosyltransferases encoded by this gene locus have been identified. STUDY
      DESIGN AND METHODS: Three unrelated patients from Germany, Turkey, and Bosnia who
      were diagnosed as having variant A subgroups were subjected to extended ABO
      typing. Serologic investigations were performed with standard methods. The
      genetic basis of the ABO phenotypes was determined by haplotype-specific sequence
      analysis of the last two exons (exons 6 and 7) of ABO and the intervening intron.
      RESULTS: The RBCs of all three patients showed serologic A characteristics being
      similar to subgroup A(x). The serum of all three patients contained weakly
      reactive anti-A. In all three patients, sequence analysis indicated an A allele
      with a nucleotide sequence identical to ABO(*)A101 except for a single-base
      substitution in exon 7 at position 502, where C was replaced by G. This point
      mutation resulted in an amino acid exchange from arginine to glycine at position
      168. The nucleotide sequence of intron 6 of the A allele was found to be
      identical to the ABO(*)A101 sequence in each patient. CONCLUSION: This study
      suggests that a variant A phenotype can arise from the new R168G polymorphism,
      reflecting the importance of this region for the ABO transferase efficiency.

PMID- 11961234
TI  - Platelet transfusion refractoriness caused by a mismatch in HLA-C antigens.
AB  - BACKGROUND: HLA-C antigens have been thought to be of little significance in
      determining the efficacy of platelet transfusions. However, six alloimmunized
      patients were encountered who were refractory to platelet transfusions because of
      anti-HLA-Cw3, -Cw3, -Cw7, or -Cw8. STUDY DESIGN AND METHODS: Between 1995 and the
      present, 88 patients with hematologic malignancies became refractory to random
      donor platelet transfusions due to HLA antibodies. HLA-A- and HLA-B-compatible
      platelet transfusions were successful in boosting platelet levels with 82 of the
      patients. This study concerns the remaining six HLA-immunized patients who were
      refractory to HLA-A- and HLA-B-compatible platelet transfusions. The response to
      the platelet transfusions was assessed by calculating both 1- and 24-hour
      posttransfusion CCIs for each transfusion. RESULTS: The average CCI(1 hour) and
      CCI(24 hours) in all patients were 20.0 and 12.8 for HLA-A-, HLA-B-, and HLA-C
      compatible transfusions and were 1.4 and 1.2 for HLA-A- and HLA-B-compatible but
      HLA-C-incompatible transfusions, respectively (p < 0.001). CONCLUSION: These
      findings clearly indicate that matching of the HLA-C antigens is also required in
      some alloimmunized patients to obtain the effectiveness of platelet transfusions.

PMID- 11961235
TI  - Flow cytometric monocyte phagocytic assay for predicting platelet transfusion
      outcome.
AB  - BACKGROUND: A new flow cytometric monocyte phagocytic assay (FMPA) was developed
      with 5-chloromethyl fluorescein diacetate (CMFDA)-labeled platelets for
      predicting the outcome of platelet transfusion. STUDY DESIGN AND METHODS: Twelve
      patients with a history of multiple platelet transfusions and 21 controls were
      enrolled in this study. Platelets labeled with CMFDA were incubated with patient
      serum and then incubated with monocytes. They were then analysed by flow
      cytometry. Monocytes that had phagocytized platelets (%) were detected as a CMFDA
      positive platelet population with a CD14+ monocyte gate. The performance of FMPA
      was evaluated in 29 transfusions by 1- and 24-hour CCIs and platelet
      crossmatching. RESULTS: FMPA results were well correlated with 1-hour (r = 
      0.818, p = 0.001) and 24-hour (r = -0.782, p = 0.001) CCIs. In the group with
      high FMPA results (mean +/- SD, 79.1 +/- 7.3%), nine of 10 positive crossmatches
      revealed low CCIs, and six of seven negative crossmatches revealed high CCIs. The
      CCI predictability of crossmatching in the group with high FMPA results was high
      (88.2%). In the group with low FMPA results (mean +/- SD, 34.6 +/- 7.8%), all 12
      transfusions revealed high CCIs even though in four transfusions there were
      positive results in both platelet antibody testing and platelet crossmatching.
      CONCLUSION: FMPA is designed with near in vivo conditions to measure an immune
      response to transfused platelets, including phagocytosis. This is a useful method
      for predicting the outcome of platelet transfusion.

PMID- 11961236
TI  - Frequency distribution of antigens in the human platelet antigen-1 system in the
      western Indian population.
AB  - BACKGROUND: Neonatal alloimmune thrombocytopenic purpura (NAITP) occurring
      because of fetomaternal incompatibility in the human platelet antigen-1 (HPA-1)
      system is increasingly being detected worldwide. Several studies have reported
      the frequency and distribution of HPA-1 alleles in different countries and ethnic
      populations. A paucity of data regarding the frequency of the antigens in the HPA
      1 system in the Indian population prompted an undertaking of this study. The
      molecular method of genotyping the platelet antigens is preferred to serology. It
      will enable future prenatal diagnosis in mothers suspected to have NAITP so that
      they can be managed better. STUDY DESIGN AND METHODS: Five hundred six unrelated
      subjects were screened for the alleles in the HPA-1 system, of which 185 were
      healthy males and 321 were females. DNA was extracted from the peripheral blood
      WBCs of these subjects, followed by PCR amplification and agarose gel
      electrophoresis of the PCR-amplified products. RESULTS: Four hundred two out of
      506 subjects (79.44%) were found to be homozygous for HPA-1a. Ninety-nine
      subjects (19.57%) were heterozygous HPA-1a/HPA-1b, and five subjects out of 506
      (0.99%) were homozygous for HPA-1b. CONCLUSION: Homozygosity for HPA-1b exists in
      the Indian population at a frequency of 0.99 percent, whereas homozygosity for
      HPA-1a is present in approximately 79 percent of the population. Hence, 0.98 x
      0.79 of the females (0.77%) in the reproductive age group are likely to be
      pregnant with an HPA-1a-positive fetus, leading to a setting in which NAITP might
      develop. The development of NAITP also depends on the HLA type of the mother;
      nevertheless, the number of pregnancies in which the fetus is at risk for NAITP
      in India is quite significant.

PMID- 11961237
TI  - Human plasma thrombopoietin levels are regulated by binding to platelet
      thrombopoietin receptors in vivo.
AB  - BACKGROUND: Data from several studies support the hypothesis that thrombopoietin
      (TPO) plasma levels are regulated via circulating platelet (PLT) numbers by
      binding to PLT TPO receptors (TPO-Rs). In this study, PLT numbers and TPO plasma
      levels were measured following the transfusion of unmanipulated, sham-saturated,
      and TPO-R-saturated PLT preparations to provide additional in vivo evidence for
      this regulatory mechanism. STUDY DESIGN AND METHODS: Following in vitro
      experiments to characterize pegylated recombinant human megakaryocyte growth and
      development factor (PEG-rHuMGDF) binding characteristics, PLT numbers and TPO
      plasma levels were measured following the transfusion of unmanipulated, sham
      saturated, and TPO-R-saturated PLT preparations in thrombocytopenic patients.
      Sham-saturated and TPO-R-saturated PLTs were prepared by a 1-hour incubation
      without and with 40 ng per mL of PEG-rHuMGDF, respectively, and subsequent
      washing and resuspension. RESULTS: In vitro, 2.72 +/- 0.8 ng of PEG-rHuMGDF per 1
      x 10(8) PLTs was bound within 1 hour of incubation. No additional PEG-rHuMGDF was
      bound following a second incubation with PEG-rHuMGDF, and bound PEG-rHuMGDF was
      not released over time. In vivo, TPO plasma levels decreased significantly (p <
      0.001), by 30.7 +/- 5.8 and 20.9 +/- 2.1 percent after transfusion of
      unmanipulated and sham-saturated PLT preparations, respectively. However, TPO
      plasma levels were unaffected after the transfusion of TPO-R-saturated PLTs
      despite comparable transfusion-induced PLT count increases. CONCLUSION: These
      data strongly support the concept that binding to PLT TPO-R is directly involved
      in human TPO plasma level regulation in vivo.

PMID- 11961238
TI  - Rapid down modulation of P-selectin glycoprotein ligand-1 (PSGL-1, CD162) by G
      CSF in humans.
AB  - BACKGROUND: In vitro and animal studies suggest a critical role for P-selectin
      glycoprotein ligand-1 (PSGL-1) in the regulation of WBC adhesion and neutrophil
      counts. As WBC activation decreases PSGL-1 expression on WBCs in vitro, the
      effects of G-CSF on PSGL-1 expression were examined. STUDY DESIGN AND METHODS:
      Two different G-CSF doses (1 and 5 microg/kg IV) were compared with high-dose
      dexamethasone (1 mg/kg twice daily) and placebo in a randomized, double-blind,
      four-way cross-over trial in eight healthy volunteers. Surface expression of WBC
      adhesion molecules was quantified by flow cytometry. RESULTS: Both G-CSF and
      dexamethasone led to a delayed down regulation of L-selectin. In contrast, G-CSF
      rapidly down regulated PSGL-1 expression on neutrophils within 90 minutes,
      whereas neither dexamethasone nor placebo had an effect. Similarly, incubation of
      WBCs with clinically relevant G-CSF concentrations (60 microg/L) for 90 minutes
      down modulated PSGL-1 expression on neutrophils and enhanced CD11b expression,
      compatible with a direct PSGL-1 down regulation by G-CSF-induced neutrophil
      activation. Similar to G-CSF, GM-CSF down regulated PSGL-1 in vitro. Both drugs
      induced shedding of soluble PSGL-1, supporting the concept that proteolytic
      cleavage is a potential mechanism of PSGL-1 down regulation on neutrophils.
      CONCLUSION: G-CSF, but not dexamethasone, down regulates PSGL-1 expression on the
      surface of neutrophils in humans. This could also partly explain the synergistic
      effects when both drugs are combined for optimal mobilization of neutrophils for
      clinical granulocyte transfusion programs.

PMID- 11961239
TI  - Cellular prion protein is expressed on endothelial cells and is released during
      apoptosis on membrane microparticles found in human plasma.
AB  - BACKGROUND: Blood and plasma of animals experimentally infected with
      transmissible spongiform encephalopathies (TSEs) can transmit TSE infection by
      transfusion. A conformational isoform of prion protein (PrPsc) is believed to be
      the TSE-infectious agent that propagates by converting the cellular prion protein
      (PrPc) to additional molecules of PrPsc. In orally infected animals, PrPsc
      accumulates in intestinal endothelial cells. In blood, two thirds of PrPc resides
      in plasma, but its source is not known. STUDY DESIGN AND METHODS: The expression
      of PrPc in cultured human umbilical vein endothelial cells (HUVECs) was studied
      using flow cytometry, immunoblotting, and RT-PCR. Flow cytometry was used to
      characterize endothelial membrane microparticles (MPs) in cell culture
      supernatants and in normal human plasma. RESULTS: HUVECs and bovine aorta
      endothelial cells express PrPc. The number of surface PrPc molecules per cell in
      HUVECs was 58,000 +/- 2,800. The induction of apoptosis in HUVECs led to a marked
      release of membrane MPs (60,000-80,000 MPs/10(3) cells) that expressed PrPc and
      other endothelial antigens. The presence of endothelial cell-derived MPs
      expressing PrPc was demonstrated in platelet-free human plasma. CONCLUSION:
      Endothelial cell apoptosis is associated with the release of PrPc-positive MPs.
      These MPs contribute to the PrPc pool in plasma and may have a role in
      disseminating TSE infectivity in blood.

PMID- 11961240
TI  - Volume of RBCs, 24- and 48-hour posttransfusion survivals, and the lifespan of
      (51)Cr and biotin-X-N-hydroxysuccinimide (NHS)-labeled autologous baboon RBCs:
      effect of the anticoagulant and blood pH on (51)Cr and biotin-X-NHS elution in
      vivo.
AB  - BACKGROUND: The RBC injury that occurs during collection of the first few
      milliliters of blood into the pH 5.0 ACD (NIH, Formula A) is referred to as the
      lesion of collection. The RBC injury was evaluated by labeling the ACD RBCs with
      (51)Cr and measuring the 24-hour posttransfusion survival. The effect of the
      acidification of ACD blood on the in vivo elution of (51)Cr from the RBC has not
      been reported. STUDY DESIGN AND METHODS: Baboon blood was collected in heparin
      and in ACD and CP2D at different ratios of blood to anticoagulant. ACD blood with
      a pH of 5.7 to 6.9 was labeled with (51)Cr. Heparinized blood with a pH of 7.4
      was labeled with biotin-X-N-hydroxysuccinimide (NHS). ACD blood with a pH of 5.9
      was labeled with both (51)Cr and biotin-X-NHS. The RBC volumes, 24- and 48-hour
      posttransfusion survivals, and lifespans (T50) were measured. RESULTS: The RBC
      volume of ACD blood with a pH ranging from 5.7 to 6.9 was not affected by (51)Cr
      labeling. (51)Cr-labeled ACD blood with a pH of 6.9 had an RBC volume that was
      significantly greater than that seen in heparinized blood with a pH of 7.4
      labeled with biotin-X-NHS. In vivo elution of (51)Cr from the RBCs prepared from
      the ACD blood with a pH of 5.7 to 6.9 and in vivo elution of biotin-X-NHS from
      RBCs prepared from ACD blood with a pH of 5.9 were associated with reductions in
      24- and 48-hour posttransfusion survivals and T50. CONCLUSIONS: The anticoagulant
      and the pH of the medium in which the RBCs were labeled with (51)Cr or biotin-X
      NHS affected in vivo elution of the label from the RBCs and may reduce
      posttransfusion survival values.

PMID- 11961241
TI  - Detection of HCV core antigen in human serum and plasma with an automated
      chemiluminescent immunoassay.
AB  - BACKGROUND: Currently, the detection of HCV infection in blood donors relies on
      the ability of immunoassays to detect circulating HCV antibodies. However, a
      significant delay exists between the time of infection and the development of
      antibodies. This delay (window period) can last up to 70 days. The introduction
      of NAT for the detection of HCV RNA has reduced this window period dramatically.
      However, NAT is labor intensive, prone to contamination, and expensive as
      compared with standard serologic tests. STUDY DESIGN AND METHODS: An automated,
      microparticle-based chemiluminescent assay for the detection of HCV core antigen
      in human serum and plasma was developed. The specificity and sensitivity of this
      prototype assay were evaluated by testing a population of normal blood donors and
      commercially available seroconversion panels. RESULTS: The HCV core antigen assay
      exhibited a 99.9-percent specificity by detecting a single repeatably reactive
      sample out of 1004 normal donors tested. Assay sensitivity was determined by
      comparing the HCV core antigen detection rate with the antibody seroconversion
      profile and the rate of HCV RNA detection. Among 15 seroconversion panels
      examined, core antigen was detected in 69 of 70 antibody-negative and/or RNA
      positive samples for a sensitivity relative to NAT of 98.6 percent. CONCLUSION:
      These data indicate that the automated, microparticle-based chemiluminescent HCV
      core antigen assay can reduce the window period for detection of potentially
      infected blood donors by 32.7 days, and it represents a viable alternative to HCV
      RNA testing.

PMID- 11961242
TI  - Potential value of Plasmodium falciparum-associated antigen and antibody
      detection for screening of blood donors to prevent transfusion-transmitted
      malaria.
AB  - BACKGROUND: Malaria antibody detection is a valuable tool in the prevention of
      transfusion-transmitted malaria in countries with a high proportion of donors
      with travel exposure to malaria. The immunofluorescent antibody test (IFAT) is
      still the reference method, but it is not suitable for screening of blood donors.
      ELISA would be an interesting alternative to the IFAT, but it lacks sensitivity.
      STUDY DESIGN AND METHODS: To evaluate the potential value of a combined screening
      strategy based on malaria antigen and antibody detection, plasma samples from 203
      patients infected with Plasmodium falciparum were tested with an ELISA for the
      detection of malaria antibodies (Malaria IgG CELISA, Cellabs) and a P. falciparum
      histidine-rich protein-2 kit (Malaria P.f., ICT Diagnostics) for the detection of
      malaria antigens. RESULTS: Among patients with positive IFAT results, CELISA had
      a sensitivity of 71 percent, whereas the combined screening tests (CELISA and
      Malaria P.f.) had a sensitivity of 88 percent (p < 0.001). Sequential samples
      from 50 patients were tested. The combined screening tests shortened the
      detection of seroconversion from 11.4 +/- 1.6 to 5.3 +/- 1.1 days (p < 0.001).
      CONCLUSION: Combined malaria antigen and antibody detection, with methods
      compatible with mass screening, may constitute an attractive alternative to the
      IFAT for blood donor screening.

PMID- 11961243
TI  - Donor anti-Jk(a) causing hemolysis in a liver transplant recipient.
AB  - BACKGROUND: Hemolytic transfusion reactions have been observed in recipients of
      ABO- and/or D-mismatched marrow, peripheral blood, and solid organs. Passenger
      lymphocyte syndrome occurs when immunocompetent donor lymphocytes transferred
      during transplantation produce alloantibodies against host antigens. CASE REPORT:
      The first case of a delayed, anti-Jk(a)-mediated hemolytic reaction in a liver
      transplant recipient, caused by passenger donor lymphocytes, is reported here. A
      43-year-old man underwent liver transplantation. Six weeks later, the patient
      underwent a second liver transplant. On Day 10 of the second transplant, clinical
      hemolysis ensued; anti-Jk(a) was detected. The patient's DAT became positive, and
      anti-Jk(a) was eluted from his RBCs. On Day 35 of the patient's second
      transplant, 3 weeks after the last blood transfusion, the patients' DAT was still
      weakly positive with anti-Jk(a) in the eluate. Six months later, serum antibody
      screening was negative, but the DAT was still weakly positive. The patient's RBCs
      tested Jk(a+), whereas the second donor's RBCs were Jk(a-). CONCLUSION: This is
      the first documentation of clinically significant hemolysis caused by anti-Jk(a),
      produced by passenger lymphocytes transferred from the donor's liver to the
      transplant recipient.

PMID- 11961244
TI  - Reticulated platelets predict platelet count recovery following chemotherapy.
AB  - BACKGROUND: A laboratory measure that predicted the timing of platelet recovery
      after chemotherapy could guide prophylactic platelet transfusion. Reticulated
      platelets (RPs) are the youngest circulating platelets; an increased percentage
      of RPs is diagnostic of increased marrow platelet production, such as seen with
      idiopathic thrombocytopenic purpura, whereas a low percentage of RPs with
      thrombocytopenia indicates marrow suppression. This study examined whether the
      percentage of RPs, in combination with a newly devised measurement of "stress
      thrombopoiesis," the RP maturation index (RP-MI), could predict platelet count
      recovery following chemotherapy-induced thrombocytopenia. STUDY DESIGN AND
      METHODS: Platelet count nadirs were retrospectively determined in 35 chemotherapy
      induced thrombocytopenia patients; percentage of RPs and RP-MI values were
      assayed at the early nadir (no imminent platelet recovery) and the late nadir
      (imminent platelet recovery). The latter was defined by a platelet count increase
      of 20 x 10(9) per L or more in the subsequent 48 hours without platelet
      transfusion. RESULTS: Early in the nadir (when platelet recovery did not occur in
      the subsequent 48 h after sampling), a low RP-MI and a low percentage of RPs were
      found in 29 of 35 patients. Late in the nadir, when recovery was imminent, 27 of
      30 evaluable patients had elevated percentages of RPs or RP-MI values; the mean
      time from sampling to an increase of 20 x 10(9) per L or more was 42 hours. The
      positive and negative predictive values of this assay were 82 and 91 percent,
      respectively. Furthermore, when thrombocytopenia was severe (platelet count < or
      = 20 x 10(9)/L), an elevated RP-MI and/or percentage of RPs correctly predicted
      imminent platelet count recovery in five of five patients. CONCLUSION: This
      noninvasive, rapid, whole-blood assay of stress thrombopoiesis provides
      reproducible indices for timing platelet recovery following chemotherapy and the
      potential to optimize the use of prophylactic platelet transfusions in
      chemotherapy patients.

PMID- 11961245
TI  - Response to vWF-coated beads and soluble p-selectin to characterize apheresis
      platelets: a comparison of three cell separators.
AB  - BACKGROUND: Plateletpheresis technologies differ among various cell separators.
      Differences in centrifugation force, centrifugation time, and platelet
      concentration in the platelet concentrate may affect platelet activation and
      function. STUDY DESIGN AND METHODS: In a three-way crossover design, 12 donors
      were randomly assigned to three types of cell separators, two continuous flow
      systems (Amicus DN, Fenwall Division, Baxter and Spectra LRS, Gambro BCT) and one
      intermittent flow system (MCS+, Haemonetics). The response to vWF-coated beads
      was determined in the peripheral blood and fresh platelet concentrates to obtain
      information about the initiating step of platelet aggregation, that is, platelet
      adhesion. Levels of soluble p-selectin were measured as a marker of platelet
      activation. RESULTS: Platelet yield and concentration of platelets were higher in
      platelet concentrates obtained with the Amicus DN than with the Spectra LRS or
      the MCS+. Maximal aggregation was significantly higher in platelets from the
      Amicus DN than in platelets from the Spectra LRS or the MCS+. Higher
      concentrations of soluble p-selectin were seen in platelet concentrates obtained
      with the Amicus DN than in concentrates from the Spectra LRS or the MCS+, but
      they did not differ after correction for the number of platelets per component.
      CONCLUSIONS: Different plateletpheresis procedures induced distinct changes of
      platelet function. Platelets collected using the Amicus DN retained the strongest
      adhesion capacity irrespective of their activation.

PMID- 11961246
TI  - Bacterial contamination of blood components needs to be confirmed.

PMID- 11961247
TI  - Leishmania donovani transmission by packed RBC transfusion to anemic dogs in the
      United States.

PMID- 11961248
TI  - A new mutation detected in RhAG of a Japanese family with Rh(mod) syndrome may
      form a longer RhAG protein.

PMID- 11961249
TI  - Evaluation of fructose diphosphate in RBC preservation.

PMID- 11961250
TI  - The VP1 capsid protein of adeno-associated virus type 2 is carrying a
      phospholipase A2 domain required for virus infectivity.
AB  - The unique region of the VP1 protein of parvoviruses was proposed to contain a
      parvoviral phospholipase A2 (pvPLA2) motif. Here, PLA2 activity is shown in the
      unique region of adeno-associated virus type 2 (AAV-2) VP1 when expressed as an
      isolated domain in bacteria. Mutations in this region of the capsid protein
      strongly reduced the infectivity of mutant virions in comparison to wild-type AAV
      2. This correlated with effects on the activity of PLA2. The mutations had no
      influence on capsid assembly, packaging of viral genomes into particles or
      binding to and entry into HeLa cells. However, a delayed onset and reduced amount
      of early gene expression, as measured by Rep immunofluorescence, was observed.
      These results suggest that pvPLA2 activity is required for a step following
      perinuclear accumulation of virions but prior to early gene expression.

PMID- 11961251
TI  - Cloning and sequencing of TT virus genotype 6 and expression of antigenic open
      reading frame 2 proteins.
AB  - The near-full-length genome of a TT virus (TTV) (HEL32), closely related to the
      previously uncharacterized genotype 6, was cloned and sequenced. The genomic
      organization of HEL32 was compared to 41 published near-full-length TTV sequences
      representing 17 genotypes. In the majority of genomes, the open reading frame
      (ORF) 2 region was divided into two separate ORFs, 2a and 2b. The ORF2a sequence
      was conserved among all genotypes, while the ORF2b region showed more
      variability. The two corresponding putative proteins of HEL32 were expressed in
      prokaryotes and their antigenic potential was studied. IgM and IgG antibodies to
      the respective ORF2-encoded proteins, fp2a and fp2b, and the presence of TTV DNA
      were studied in the sera of 89 constitutionally healthy adults. By immunoblot
      using the small TTV proteins as antigens, strong IgM and IgG reactivities were
      found in 9 and 10% of subjects, respectively. Follow-up studies for 12-15 years
      of three subjects showed either a persistent coexistence of IgM and TTV DNA or
      the appearance of viral DNA regardless of pre-existing antibodies. The low
      prevalence of IgG could be due to the weak immunogenicity of these probably non
      structural proteins or to a genotype-specific antibody response. By nested PCR of
      the conserved ORF2a region, the prevalence of TTV DNA was 85%. TTV genotype 6
      sequences were found by specific PCR in 3 of 35 (8.6%) subjects. The low
      prevalence of TTV IgG compared to the high TTV DNA prevalence, the coexistence of
      antibodies and viral DNA and the appearance of TTV DNA regardless of pre-existing
      antibodies suggest that the B-cell immunity against these minor TTV proteins
      would not be cross protective.

PMID- 11961252
TI  - Virus replication and virion export in X-deficient hepatitis B virus transgenic
      mice.
AB  - The function of the X protein (pX) in the replication cycle of mammalian
      hepadnaviruses is enigmatic. Using tissue culture experiments it has been shown
      that the X gene product is not central to hepatitis B virus (HBV) replication and
      virion export. However, at present it is still unclear whether this also applies
      to the in vivo situation. Using a terminally redundant X-deficient HBV DNA
      construct, transgenic mice were established that exhibited high-level expression
      of the viral core protein in liver and kidneys. Importantly, replicative DNA
      intermediates and mature viral genomes could be detected in the liver and serum
      of these mice, respectively. These findings indicate that, in the in vivo model
      of transgenic mice, the HBV X (HBx) gene product is not required for HBV
      replication and virion secretion.

PMID- 11961253
TI  - The products of the UL10 (gM) and the UL49.5 genes of Marek's disease virus
      serotype 1 are essential for virus growth in cultured cells.
AB  - The role of the products of the UL10 and the UL49.5 homologous genes of Marek's
      disease virus serotype 1 (MDV-1) in virus replication was investigated. Deletion
      of either open reading frame in an infectious bacterial artificial chromosome
      clone (BAC20) of MDV-1 resulted in progeny viruses that were unable to spread
      from cell to cell. After transfection of UL10- or UL49.5-negative BAC20 DNA into
      chicken or quail cells, only single infected cells were observed by indirect
      immunofluorescence analysis. In contrast, plaque formation was restored when
      mutant BAC DNAs were co-transfected with the corresponding expression plasmid
      encoding either the UL10-encoded gM or the UL49.5 gene product. These data
      demonstrate that gM and its putative complex partner, the UL49.5 homologous
      protein, are essential for MDV-1 growth in cultured cells. Thus, MDV-1 represents
      the first example of a member of the family Herpesviridae for which the highly
      conserved membrane proteins are indispensable for cell-to-cell spread.

PMID- 11961254
TI  - Analysis of intracellular and intraviral localization of the human
      cytomegalovirus UL53 protein.
AB  - Human cytomegalovirus (HCMV) UL53 belongs to a family of conserved herpesvirus
      genes. In this work, the expression and localization of the UL53 gene product was
      analysed. Results obtained showed that pUL53 is a new structural protein. In
      infected human fibroblasts, pUL53 localizes in cytoplasmic perinuclear granular
      formations together with other structural viral proteins. In the nucleus, pUL53
      forms patches at the nuclear periphery and co-localizes with lamin B at the
      internal nuclear membrane level. Immunoelectron microscopy studies have disclosed
      that nuclear pseudo-inclusions are labelled, whereas nucleocapsid formations
      within the intranuclear skein are negative. Furthermore, the mature virus
      particle maintains pUL53 at its tegumental level. These data suggest that pUL53
      could be involved either in nucleocapsid maturation or in the egress of
      nucleocapsids from the nucleus to the cytoplasm through the nuclear membrane, a
      role compatible with the function hypothesized for UL31, its positional homologue
      in herpes simplex virus type 1.

PMID- 11961255
TI  - Direct targeting of human cytomegalovirus protein kinase pUL97 by kinase
      inhibitors is a novel principle for antiviral therapy.
AB  - The protein kinase pUL97, encoded by human cytomegalovirus (HCMV), is an
      important determinant of virus replication. Recently, indolocarbazoles were
      identified as a class of substances that inhibit the pUL97 kinase activity in
      vitro. In parallel, it was shown that indolocarbazoles interfere with HCMV
      replication; however, the causal relationship between inhibition of pUL97 kinase
      activity and virus replication has not been clarified. Here evidence is provided
      that indolocarbazole-mediated inhibition of virus replication is a direct result
      of diminished pUL97 protein kinase activity. In cell culture infections, a strong
      and selective antiviral activity was measured with respect to several strains of
      HCMV in contrast with other related or non-related viruses. For fine
      quantification, recombinant HCMVs expressing green fluorescent protein were used,
      demonstrating the high sensitivity towards compounds NGIC-I and Go6976.
      Interestingly, a ganciclovir-resistant virus mutant (UL97-M460I) showed increased
      sensitivity to both compounds. Supporting this concept, transfection experiments
      with cloned pUL97 revealed that ganciclovir-resistant mutants were characterized
      by reduced levels of autophosphorylation compared with wild-type and possessed
      particularly high sensitivity to indolocarbazoles. Moreover, the Epstein-Barr
      virus-encoded homologous kinase, BGLF4, which showed a similar pattern of
      autophosphorylation and ganciclovir phosphorylation activities, was not
      inhibited. Importantly, a cytomegalovirus deletion mutant, lacking a functional
      UL97 gene and showing a severe impairment of replication, was completely
      insensitive to indolocarbazoles. Thus, our findings indicate that a specific
      block in the activity of pUL97 is the critical step in indolocarbazole-mediated
      inhibition of virus replication and that pUL97 might be targeted very efficiently
      by a novel antiviral therapy.

PMID- 11961256
TI  - Epstein-Barr virus latent membrane protein 2B (LMP2B) co-localizes with LMP2A in
      perinuclear regions in transiently transfected cells.
AB  - Epstein-Barr virus is a human gammaherpesvirus that infects and establishes
      latency in B lymphocytes in vivo. The latent membrane protein 2 (LMP2) gene is
      expressed in latently infected B cells and encodes two protein isoforms, LMP2A
      and LMP2B, that are identical except for an additional N-terminal 119 aa
      cytoplasmic domain which is present in the LMP2A isoform. A panel of fusion
      proteins was constructed in which the fluorescent enhanced green fluorescent
      protein and DsRed protein domains were fused to the N- and C-termini of LMP2A and
      LMP2B. By fluorescence microscopy, LMP2B localized to perinuclear regions of both
      live and fixed transiently transfected cells. Co-localization was detected with
      markers for the endoplasmic reticulum and the trans-Golgi network. No evidence of
      co-localization of LMP2B with endosomes or surface expression was obtained.
      Transiently expressed LMP2B co-localized with transiently or constitutively
      expressed LMP2A. Confocal microscopy confirmed that LMP2A proteins localized to
      intracellular perinuclear compartments with markers for the trans-Golgi network.
      Only LMP2A proteins with C-terminal truncations were detected in the plasma
      membrane with extracellular loop1 epitope tags. These results indicate that the
      transmembrane domain of LMP2 proteins possess intracellular retention signals and
      suggest that LMP2A-mediated signalling effects are likely to be ectopic,
      originating from sites inside the cell close to the nucleus.

PMID- 11961258
TI  - Orf virus encodes a functional dUTPase gene.
AB  - The present study is the first report on the functional activity of a
      parapoxvirus-encoded dUTPase. The dUTPase gene of the attenuated orf virus
      (ORFV), strain D1701, was expressed as a bacterial thioredoxin fusion protein. In
      vitro assays showed that ORFV dUTPase was highly specific for dUTP as substrate.
      The enzyme was active over a broad pH range (pH 6.0-9.0), with maximal enzymatic
      activity at pH 7.0 in the presence of Mg(2+) cations. Kinetic studies of the
      recombinant ORFV dUTPase revealed an apparent K(m) of 4.0 microM, which is more
      similar to that of the mammalian or African swine fever virus enzyme than to the
      K(m) of vaccinia virus dUTPase. Enzyme activity was also found with purified ORFV
      particles, indicating its virion association.

PMID- 11961257
TI  - Lysine residues of Epstein-Barr virus-encoded nuclear antigen 2 do not confer
      secondary modifications via ubiquitin or SUMO-like proteins but modulate
      transcriptional activation.
AB  - Epstein-Barr virus nuclear antigen 2 (EBNA2) is essential for transformation
      through activation of viral and cellular genes. Within 487 residues, EBNA2
      contains six lysine (K) residues (positions 335, 357, 359, 363, 366 and 480),
      which were mutated to arginine (R) residues, either individually or in
      combination, and tested for subcellular localization, mobility by SDS-PAGE and
      transactivation of three promoters. All mutants featuring the K(480)R mutation
      within the nuclear localization signal were partially cytoplasmic with a reduced
      level of transactivation of the latent membrane protein 1 (LMP1) promoter (-327
      to +40). The K(366)R mutation also showed a decrease in transactivation of a
      promoter consisting only of 12 recombination signal-binding protein-Jkappa
      binding sites, while all mutants with the K(335)R exchange showed a markedly
      elevated transactivation with the -327 to +40 construct and all mutants showed
      slightly reduced transactivation with a -634 to +40 LMP1 promoter. None of the
      mutants exhibited altered migration in SDS-PAGE, excluding secondary
      modification, i.e. through SUMO-like proteins.

PMID- 11961259
TI  - Orf virus-encoded interleukin-10 stimulates the proliferation of murine mast
      cells and inhibits cytokine synthesis in murine peritoneal macrophages.
AB  - Orf virus (ORFV) is the type species of the parapoxvirus genus and produces
      cutaneous pustular lesions in sheep, goats and humans. The genome encodes a
      polypeptide with remarkable homology to interleukin-10 (IL-10), particularly
      ovine IL-10, and also to IL-10-like proteins encoded by Epstein-Barr virus (EBV)
      and equine herpesvirus. IL-10 is a pleiotropic cytokine that can exert either
      immunostimulatory or immunosuppressive effects on many cell types. We have
      expressed and purified C-terminal FLAG and His(6)-tagged versions of ORFV-IL-10
      and shown that ORFV-IL-10 costimulates murine mast cells (MC/9) and inhibits
      tumour necrosis factor-alpha synthesis in activated mouse peritoneal macrophages.
      Our results demonstrate that although ORFV-IL-10 is structurally similar to EBV
      IL-10 it has evolved a different spectrum of activities. EBV-IL-10 does not
      stimulate the proliferation of thymocytes or mast cells whereas ORFV-IL-10 has
      both of these activities. Recent studies show that the critical difference in
      molecular structure of human IL-10 and EBV-IL-10, which may be the basis of their
      functional differences, is linked to a single amino acid substitution. Consistent
      with the activity spectrum reported here for ORFV-IL-10, the viral gene encodes
      the critical amino acid seen in human IL-10. Although the ORFV-IL-10 gene has
      clearly undergone significant evolutionary change at the nucleotide level
      compared with ovine IL-10, it has largely retained the polypeptide structure and
      functional characteristics of its ovine counterpart, suggesting that mutations of
      the gene to a potentially more potent immunosuppressive form may compromise the
      co-existence of host and virus.

PMID- 11961260
TI  - Administration to mice of a monoclonal antibody that neutralizes the
      intracellular mature virus form of vaccinia virus limits virus replication
      efficiently under prophylactic and therapeutic conditions.
AB  - The WHO smallpox eradication program was concluded 21 years ago and the non
      vaccinated population is now at risk of poxvirus infections, either by contact
      with monkeypox or through bioterrorism. Since drugs specific against poxvirus
      infections are limited, neutralizing monoclonal antibodies (mAbs) that are
      effective in vivo may be an important tool in controlling poxvirus infections. To
      this end, we studied the efficacy of the mAb C3, reactive against the trimeric 14
      kDa protein of vaccinia virus (VV) localized in the membrane of the intracellular
      form of mature virus, for its ability to neutralize VV infection in mice. The
      results show that prophylactic as well as therapeutic administration of mAb C3
      can be an effective means of control of VV replication within the host. The
      interval of antibody efficacy following a single administration, before and after
      VV inoculation, has been defined. This study reinforces the notion that
      neutralizing mAbs should be developed to control health-related human infections
      by poxviruses.

PMID- 11961261
TI  - Identification and localization of a prawn white spot syndrome virus gene that
      encodes an envelope protein.
AB  - Among the important challenges to shrimp aquaculture worldwide are the diseases
      caused by viruses, in particular by white spot syndrome virus (WSSV), which has a
      genome estimated to contain 305 kb. By analysis and comparison of the WSSV
      genomic DNA and cDNA libraries, an ORF (vp28 gene) was identified. The gene,
      encoding a novel 204-amino-acid protein, was expressed in Escherichia coli and
      purified. A specific antibody was raised using the purified VP28 protein. After
      inoculation of healthy adult Penaeus monodon shrimp with WSSV, the gene
      transcript and VP28 protein were first detected at low levels at 6 and 18 h post
      infection, respectively. These experiments suggest that it might be a late gene.
      Immuno-electron microscopy with gold-labelled antibody revealed that the gold
      particles were distributed in the outer envelope of WSSV virions and showed that
      vp28 encodes a virus envelope protein.

PMID- 11961262
TI  - Characterization of two genes of the polydnavirus of Chelonus inanitus and their
      stage-specific expression in the host Spodoptera littoralis.
AB  - Chelonus inanitus (Braconidae, Hymenoptera) is a solitary egg-larval parasitoid
      of Spodoptera littoralis. Along with the egg the female wasp injects
      polydnaviruses, which are prerequisites for successful parasitoid development.
      The polydnavirus genome is segmented and consists of double-stranded circular
      DNA. Proviral DNA is integrated in the wasp's genome; virus replication is
      restricted to the wasp's ovary and does not occur in the parasitized host. The
      polydnavirus of C. inanitus (CiV) protects the parasitoid larva from
      encapsulation by the host's immune system and causes a developmental arrest of
      the host in the prepupal stage. Here we report on the first two cloned CiV genes,
      which are named CiV14g1 and CiV14g2 because of their localization on segment
      CiV14. The cDNA of CiV14g1 has a size of 2036 bp; the gene contains seven exons
      interrupted by six introns of similar size and encodes a putative polypeptide of
      548 amino acids. The cDNA of CiV14g2 has a size of 618 bp; the gene consists of
      three exons and encodes a putative peptide of 77 amino acids. Transcript
      quantities of both genes are very low up to the penultimate larval instar of the
      host. In the last instar, at the stage of pupal cell formation, CiV14g1
      expression increases about 5-fold and CiV14g2 expression about a 1000-fold. These
      are the first data to show strong upregulation of polydnavirus genes towards the
      end of parasitization. These two genes might be involved in the reduction of host
      ecdysteroids observed at this stage.

PMID- 11961263
TI  - Restriction of poliovirus RNA replication in persistently infected nerve cells.
AB  - The aetiology of post-polio syndrome may involve persistence of poliovirus (PV)
      in the CNS. PV persists in the CNS of infected paralysed mice for over a year
      after the acute phase of paralytic poliomyelitis. However, infectious PV
      particles cannot be recovered from homogenates of CNS from paralysed mice after
      the acute phase of disease, indicating that PV replication is restricted. To
      identify the molecular mechanism by which PV replication is limited, PV RNA
      synthesis was analysed by estimating the relative level of genomic (plus-strand)
      and complementary (minus-strand) PV RNA in the CNS of persistently infected mice.
      PV RNA replication decreased during the 6 months following onset of paralysis,
      due mainly to inhibition of plus-strand RNA synthesis. Thus, restriction of PV
      RNA synthesis may contribute to persistence by limiting virus replication in the
      mouse CNS. Interestingly, viral RNA replication was similarly inhibited in
      neuroblastoma IMR-32 cell cultures persistently infected with PV. This in vitro
      model thus shows that cellular factors play a role in the inhibition of viral RNA
      synthesis.

PMID- 11961265
TI  - Prevalence of vaccine-derived polioviruses in the environment.
AB  - A survey of poliovirus in river and sewage water was conducted from October 1993
      to September 1995 in Toyama Prefecture, Japan. In this study, 25 isolates
      differentiated as type 2 vaccine-derived polioviruses (VDPVs) were characterized
      using mutant analysis by PCR and restriction-enzyme cleavage (MAPREC) to estimate
      the ratio of 481-G revertants correlated to neurovirulence in a virus population.
      Of these isolates, 23 (92%) comprised between 44 and 96% 481-G revertants by
      MAPREC. The other two isolates had revertant percentages close to the 0.6% of the
      attenuated reference strain. It was presumed that these 23 isolates would be
      variant with potential neurovirulence by MAPREC analysis. Of the 23 isolates,
      three were isolated from river water. Moreover, our results by MAPREC showed that
      type 2 poliovirus was phenotypically more variable than type 1 (69%) or type 3
      (55%), as determined in previous studies. The prevalence of virulent-type VDPVs
      in river and sewage water suggested that the oral poliovaccine itself had led to
      wide environmental pollution in nature. To terminate the cycle of virus
      transmission in nature, the ecology of VDPVs should be studied further. A hygiene
      programme, inactivated poliovirus vaccine immunization and well-maintained herd
      immunity may play key roles in reducing the potential risk of infection by
      virulent VDPVs.

PMID- 11961264
TI  - Comparison of neuropathogenicity of poliovirus in two transgenic mouse strains
      expressing human poliovirus receptor with different distribution patterns.
AB  - In order to determine the influence of poliovirus receptor (PVR) expression on
      poliovirus cell tropism and neuropathogenesis, two transgenic (tg) mouse models
      were produced in which PVR was expressed under the transcriptional control of the
      human PVR gene promoter (hg-PVR mice) and the CAG promoter (CAG-PVR mice). Then
      the pathogenicity of poliovirus after intracerebral inoculation of the type 1
      Mahoney strain was compared. These showed completely different clinical and
      pathological changes. In the former, the expression of PVR in neurons in the
      central nervous system (CNS) conferred susceptibility to poliovirus, and a
      paralytic disease that resembled the human poliomyelitis occurred. In the latter,
      PVR expression was detected in glial and ependymal cells in addition to the
      neurons. Paralysis of the limbs and death were rarely observed and mice survived
      without showing substantial clinical abnormality. Histopathological examination
      revealed that glial and ependymal cells also became susceptible to poliovirus
      infection. Poliovirus antigens were mainly detected in ependymal and glial cells
      and hippocampal neurons near the lateral ventricles in the brain, but were not
      frequently detected in neurons in the brainstem unlike in the hg-PVR mice. The
      levels of viral antigens and virus recovered from the CNS of CAG-PVR mice began
      to decrease as early as 2 days after inoculation, which suggested induction of a
      fast immune response. These results suggest that the neuropathogenicity of
      poliovirus changes markedly depending on the specific expression of the PVR
      molecule in the CNS.

PMID- 11961266
TI  - Long-range RNA-RNA interactions between distant regions of the hepatitis C virus
      internal ribosome entry site element.
AB  - Efficient internal initiation of translation from the hepatitis C virus (HCV)
      internal ribosome entry site (IRES) requires sequences of domain II, but the
      precise role of these sequences is still unknown. In this study, the formation of
      RNA-RNA complexes in the HCV IRES was evaluated. Using transcripts that contain
      the sequences of the structural HCV IRES domains II, IIIabcd, IIIabc, IV and
      IIIef-IV, specific long-range interactions between domains II and IV, as well as
      domains II and IIIabcd, have been found. These interactions were readily detected
      in a gel mobility-shift assay and required the presence of magnesium ions. A high
      concentration of nonspecific competitors, an 80 nt fragment of 18S rRNA or
      poly(I:C), did not interfere with the formation of RNA complexes. Interestingly,
      an RNA oligonucleotide bearing the sequence of stem-loop IIId interacted with
      domain II but not with domain IV or IIIef-IV, strongly suggesting that the
      interaction between domains II and IIIabcd was mediated by the IIId hairpin.
      Interaction between domains IIIabcd and IV was barely detected, consistent with
      the result that the apical part of domain III folds independently of the rest of
      the IRES. Moreover, the addition of stem-loop IIIef sequences to domain IV
      significantly reduced its ability to interact, which is in agreement with the
      formation of a compact RNA structure of domain IV with IIIef. The interactions
      observed in the absence of proteins between domains II and IV as well as stem
      loop IIId and domain II may be transient, having a regulatory role in the
      translation efficiency of the HCV IRES.

PMID- 11961267
TI  - Non Fc receptor-mediated infection of human macrophages by dengue virus serotype
      2.
AB  - Four human monocyte-derived macrophage membrane proteins, with apparent molecular
      masses of 27, 45, 67 and 87 kDa, were identified as possible receptors for dengue
      virus serotype 2 (DEN-2) (Mexican isolate 200787/1983), based on affinity
      chromatography, immunofluorescence, virus overlay protein-binding assays and
      Western blotting. Additionally, mouse polyclonal antibodies raised against each
      of the four proteins were capable of partially inhibiting in vitro DEN-2
      infection of monocyte-macrophages, thus supporting the notion of a role for such
      proteins as DEN-2 receptors. Parallel studies were carried out using the human
      promonocytic U-937 cell line, both as undifferentiated cells and as monocyte-like
      phorbol myristate acetate (PMA)-differentiated cells, as target cells. Whereas
      interaction between DEN-2 and undifferentiated U-937 cells was almost negligible,
      PMA-differentiated U-937 cells were shown to harbour putative receptors (with
      molecular masses of 45 and 67 kDa) for DEN-2, similar to those found in human
      monocyte-derived macrophages. To our knowledge, this is the first report that
      describes putative receptors for DEN-2 in primary cultures of human macrophages.

PMID- 11961268
TI  - Characterization of HLA-A2.1-restricted epitopes, conserved in both Hantaan and
      Sin Nombre viruses, in Hantaan virus-infected patients.
AB  - Nine different CTL epitopes, conserved in both Hantaan virus (HTNV) and Sin
      Nombre virus (SNV), were selected for study. The binding affinity of each peptide
      with HLA-A2.1 molecules in vitro was determined and antigen-specific responses
      from seven donors who had a previous field infection with HTNV were examined.
      Although the strength or frequency of CTL activity showed different patterns in
      the seven patients, five of seven patients showed significant activity against at
      least one or more epitope peptides. In particular, the peptide ILQDMRNTI (HTNV,
      aa 334-342; SNV, aa 333-341), which elicited CTL activity in five patients, was
      shown to be specifically HLA-A2.1-restricted in partially cloned CD8+ T cells and
      also induced activated and effector CD8+ T cell-producing T cytotoxic (Tc) type 1
      cytokines, such as IL-2 and IFN-gamma. The results suggest that this epitope
      would serve as a useful component for the intervention of both HTNV and SNV
      infection.

PMID- 11961269
TI  - Effect of addition of new oligosaccharide chains to the globular head of
      influenza A/H2N2 virus haemagglutinin on the intracellular transport and
      biological activities of the molecule.
AB  - The haemagglutinin (HA) of influenza A/H2N2 virus possesses six antigenic sites
      (I-A to I-D, II-A and II-B), and sites I-A, I-B and I-C are located in the
      regions corresponding to sites A, B and D on the H3 HA. We demonstrated
      previously that most escape mutants selected by mAbs to site I-A, I-B or I-C had
      acquired a new oligosaccharide at position 160, 187 or 131, respectively, but
      this has never occurred during circulation of A/H2N2 virus in humans. Here, to
      examine whether the H2 HA has the potential to gain two new oligosaccharides on
      its tip, 31 double escape mutants were isolated by using a single escape mutant
      with an oligosaccharide at position 160, 187 or 131 as a parental virus and a mAb
      to an antigenic site different from that to which the mAb used for selection of
      the parental virus was directed as a selecting antibody, but there were no
      mutants with two new oligosaccharides. Glycosylation-site HA mutants containing
      one to three oligosaccharides at positions 160, 187 and 131 were also constructed
      and their intracellular transport and biological activities were analysed. The
      results showed that all of the mutant HAs were transported to the cell surface
      but exhibited a decrease in both receptor-binding and cell-fusing activities.
      Thus, influenza A/H2N2 virus may have failed to increase the number of
      oligosaccharides on the HA because, if this happens, the biological activities of
      the HA are reduced, decreasing the ability of the virus to replicate in humans.

PMID- 11961270
TI  - A CD46CD[55-46] chimeric receptor, eight short consensus repeats long, acts as an
      inhibitor of both CD46 (MCP)- and CD150 (SLAM)-mediated cell-cell fusion induced
      by CD46-using measles virus.
AB  - According to their cellular receptor use, measles virus (MV) strains can be
      separated into two phenotypes, CD46-using and CD46-non-using. A long chimeric
      receptor, CD46CD[55-46], was generated from the CD46 backbone, encompassing the
      four short consensus repeat (SCR) domains of CD46 linked via a flexible glycine
      hinge to SCR1 and SCR2 of CD55, SCR3 and SCR4 of CD46 and the STP, transmembrane
      and cytoplasmic tail of CD46. This chimeric receptor was proficient for MV
      binding but deficient in mediating MV-induced cell-to-cell fusion and virus
      replication, possibly due to the extended distance between the MV haemagglutinin
      (H) binding site (CD46 SCR1-SCR2) and the cell membrane. When coexpressed with
      either wild-type CD46 or CD150, this fusion-incompetent receptor exerted a
      dominant negative effect and inhibited both cell-to-cell fusion and entry of MV
      with CD46-using, but not CD46-non-using, phenotype. A soluble octameric CD46
      C4bpalpha exhibited similar CD46- and CD150-mediated fusion inhibition properties
      only against CD46-using MV. This suggests that the long CD46CD[55-46] receptor
      acts by sequestering incoming MV prior to its binding to the shorter functional
      CD46 or CD150 receptor.

PMID- 11961271
TI  - Measles virus-induced modulation of host-cell gene expression.
AB  - The influence of measles virus (MV) infection on gene expression by human
      peripheral blood mononuclear cells (PBMCs) was examined with cDNA microarrays.
      The mRNA levels of more than 3000 cellular genes were compared between uninfected
      PBMCs and cells infected with either the Edmonston MV strain or a wild-type MV
      isolate. The MV-induced upregulation of individual genes identified by microarray
      analyses was confirmed by RT-PCR. In the present study, a total of 17 genes was
      found to be upregulated by MV infection. The Edmonston strain grew better in the
      PBMC cultures than the wild-type MV, and the Edmonston strain was a stronger
      inducer of the upregulated host cell genes than the wild-type virus. The anti
      apoptotic B cell lymphoma 3 (Bcl-3) protein and the transcription factor NF
      kappaB p52 subunit were upregulated in infected PBMCs both at the mRNA and at the
      protein level. Several genes of the interferon system including that for
      interferon regulatory factor 7 were upregulated by MV. The genes for a number of
      chaperones, transcription factors and other proteins of the endoplasmic reticulum
      stress response were also upregulated. These included the gene for the pro
      apoptotic and growth arrest-inducing CHOP/GADD153 protein. Thus, the present
      study demonstrated the activation by MV of cellular mechanisms and pathways that
      may play a role in the pathogenesis of measles.

PMID- 11961272
TI  - High avidity cytotoxic T lymphocytes to a foreign antigen are efficiently
      activated following immunization with a recombinant paramyxovirus, simian virus
      5.
AB  - Our previous work has shown that high avidity cytotoxic T lymphocytes (CTL) are
      optimal for virus clearance in vivo and thus it is necessary that an effective
      vaccine is capable of eliciting high avidity CTL. To determine if vaccination
      with the paramyxovirus simian virus 5 (SV5) elicits a high avidity response to a
      model foreign antigen, a recombinant virus was engineered to express chicken
      ovalbumin (rSV5-Ova). To compare the CTL response elicited with rSV5-Ova and a
      recombinant vaccinia virus expressing ovalbumin (rVV-Ova), mice were vaccinated
      intranasally with various doses of each vector and the Ova-specific CTL response
      was determined by ELISPOT analysis. Here, it has been shown that rSV5 can be
      equally as effective as rVV in eliciting antigen-specific CTL, in terms of both
      the total number of CTL and the number of high avidity cells. This has
      implications for both the design of vaccine vectors and the route utilized for
      vaccine administration for the elicitation of high avidity CTL responses. The
      advantages and future potential use of rSV5 vaccine vectors are discussed.

PMID- 11961273
TI  - Mutational analysis of a human immunodeficiency virus type 1 Tat protein
      transduction domain which is required for delivery of an exogenous protein into
      mammalian cells.
AB  - The human immunodeficiency virus type 1 (HIV-1) Tat protein transduction domain
      (PTD), which contains a high proportion of arginine and lysine residues, is
      responsible for highly efficient protein transduction through the plasma
      membrane. To identify the role of the PTD sequence motif in transduction, various
      deletions and substitutions were introduced into the PTD. Tat-green fluorescent
      protein (GFP) fusion proteins, containing various lengths of the Tat PTD, were
      expressed and the extent of their transduction into mammalian cells was analysed
      by Western blot analysis and fluorescence microscopy. Deletion analysis of PTD
      mapped to a nine amino acid motif (residues 49-57: RKKRRQRRR) sufficient for
      transduction. Further deletion of this Tat basic domain either at the N terminus
      or at the C terminus significantly decreased transduction efficiency. The
      transduction efficiencies of GFPs fused to nine consecutive lysine (9Lys-GFP) or
      arginine (9Arg-GFP) residues were similar to that of Tat(49-57)-GFP. The
      transduced proteins localized to both the nucleus and the cytosol, as assessed by
      confocal microscopy and Western blot analysis of subcellular fractions from
      transduced cells. Thus, the availability of recombinant GFP fusion proteins
      facilitates the simple and specific identification of protein transduction
      mediated by these peptide sequences. The modified PTD sequences designed in this
      study may provide useful tools necessary for delivering therapeutic
      proteins/peptides into cells.

PMID- 11961275
TI  - Muscovy duck reovirus sigmaC protein is atypically encoded by the smallest genome
      segment.
AB  - Although muscovy duck reovirus (DRV) shares properties with the reovirus isolated
      from chicken, commonly named avian reovirus (ARV), the two virus species are
      antigenically different. Similar to the DRV sigmaB-encoded gene (1201 bp long)
      previously identified, the three other double-stranded RNA small genome segments
      of DRV have been cloned and sequenced. They were 1325, 1191 and 1124 bp long,
      respectively, and contained conserved terminal sequences common to ARVs. They
      coded for single expression products, except the smallest (S4), which contained
      two overlapping open reading frames (ORF1 and ORF2). BLAST analyses revealed that
      the proteins encoded by the 1325 and 1191 bp genes shared high identity levels
      with ARV sigmaA and sigmaNS, respectively, and to a lesser extent with other
      orthoreovirus counterparts. No homology was found for the S4 ORF1-encoded p10
      protein. The 29.4 kDa product encoded by S4 ORF2 appeared to be 25% identical to
      ARV S1 ORF3-encoded sigmaC, a cell-attachment oligomer inducing type-specific
      neutralizing antibodies. Introduction of large gaps in the N-terminal part of the
      DRV protein was necessary to improve DRV and ARV sigmaC amino acid sequence
      alignments. However, a leucine zipper motif was conserved and secondary structure
      analyses predicted a three-stranded alpha-helical coiled-coil feature at this
      amino portion. Thus, despite extensive sequence divergence, DRV sigmaC was
      suggested to be structurally and probably functionally related to ARV sigmaC.
      This work provides evidence for the diversity of the polycistronic S class genes
      of reoviruses isolated from birds and raises the question of the relative
      classification of DRV in the Orthoreovirus genus.

PMID- 11961274
TI  - Co-expression of interleukin-5 influences replication of simian/human
      immunodeficiency viruses in vivo.
AB  - The positive effect of the co-expression of T helper (Th) cell type 2 cytokine
      interleukin-5 (IL-5) on nef-deleted simian/human immunodeficiency virus (SHIV)
      replication in vitro has been observed previously. To analyse whether the growth
      advantage of IL-5-containing SHIV (NI-IL5) in vitro would be relevant in vivo,
      the virus was inoculated into monkeys. Three rhesus macaques were inoculated
      intravenously with 10(4) TCID(50) of NI-IL5. Results were compared with those
      obtained previously from SHIV NM-3rN (intact) and SHIV-dn (nef-deleted)-infected
      monkeys. Cytokine production, analysed by IL-5 ELISA, showed a twofold increase
      in IL-5 concentration in the plasma soon after the peak of virus replication.
      Virus replication and antibody production were greater in monkeys inoculated with
      IL-5-expressing SHIV than in monkeys inoculated with nef-deleted SHIV without IL
      5. These findings show a stimulation of SHIV replication by co-expression of IL-5
      and suggest the important role of Th2-type cytokines in human immunodeficiency
      virus type 1 infection.

PMID- 11961276
TI  - Initial infection of roots and leaves reveals different resistance phenotypes
      associated with coat protein gene-mediated resistance to Potato mop-top virus.
AB  - Resistance to the pomovirus Potato mop-top virus (PMTV) was studied in potato
      (Solanum tuberosum cv. Saturna) and Nicotiana benthamiana transformed with the
      coat protein (CP) gene of PMTV. The incidence of PMTV infections was reduced in
      tubers of the CP-transgenic potatoes grown in the field in soil infested with the
      viruliferous vector, Spongospora subterranea. However, in those tubers that were
      infected, all three virus RNAs were detected and virus titres were high. The CP
      transgenic N. benthamiana plants were inoculated with PMTV using two methods.
      Following mechanical inoculation of leaves, no RNA 3 (the CP-encoding RNA
      homologous to the transgene) was detected in leaves, but in some plants low
      amounts of RNA 3 were detected in roots; RNA 2 was readily detected in leaves and
      roots of several plants. Inoculation of roots using viruliferous S. subterranea
      resulted in infection of roots in all plants and the three PMTV RNAs were
      detected. However, no systemic movement of PMTV from roots to the above-ground
      parts was observed, indicating a novel expression of resistance. These data
      indicate that the CP gene-mediated resistance to PMTV specifically restricts
      accumulation of PMTV RNA 3, and is more effective in leaves than roots.
      Furthermore, expression of resistance is different depending on whether leaves or
      roots are inoculated. Data do not exclude the possibility that both a protein
      mediated and an RNA-mediated resistance mechanism are involved.

PMID- 11961277
TI  - Proteolytic processing of potyviral proteins and polyprotein processing
      intermediates in insect and plant cells.
AB  - Processing of the polyprotein encoded by Potato virus A (PVA; genus Potyvirus)
      was studied using expression of the complete PVA polyprotein or its mutants from
      recombinant baculoviruses in insect cells. The time-course of polyprotein
      processing by the main viral proteinase (NIaPro) was examined with the pulse
      chase method. The sites at the P3/6K1, CI-6K2 and VPg/NIaPro junctions were
      processed slowly, in contrast to other proteolytic cleavage sites which were
      processed at a high rate. The CI-6K2 polyprotein was observed in the baculovirus
      system and in infected plant cells. In both cell types the majority of CI-6K2 was
      found in the membrane fraction, in contrast to fully processed CI. Deletion of
      the genomic region encoding the 6K1 protein prevented proper proteolytic
      separation of P3 from CI, but did not affect processing of VPg, NIaPro, NIb or CP
      from the polyprotein. The 6K2-encoding sequence could be removed without any
      detectable effect on polyprotein processing. However, deletion of either the 6K1
      or 6K2 protein-encoding regions rendered PVA non-infectious. Mutations at the
      6K2/VPg cleavage site reduced virus infectivity in plants, but had a less
      pronounced, albeit detectable, effect on proteolytic processing in the
      baculovirus system. The results of this study indicate that NIaPro catalyses
      proteolytic cleavages preferentially in cis, and that the 6K1/CI and NIb/CP sites
      can also be processed in trans. Both 6K peptides are indispensable for virus
      replication, and proteolytic separation of the 6K2 protein from the adjacent
      proteins by NIaPro is important for the rate of virus replication and movement.

PMID- 11961278
TI  - In vivo generation of hybrids between different species of RNA phages.
AB  - Hybrids between different species or genera of the single-stranded RNA coliphages
      have not been found in nature. Here, it has been shown that viable hybrids
      between different phage species can easily be generated in the laboratory by in
      vivo recombination. cDNA of species I phage MS2 located on a plasmid and lacking
      part of its 5' untranslated leader (5' UTR) was complemented with another plasmid
      carrying the 5' half of the genome of fr, a species I phage, or of KU1, a species
      II representative with low sequence similarity. When the two plasmids were
      present in the same cell there was spontaneous production of hybrid phages.
      Interestingly, these hybrids did not arise by a double or single crossover that
      would replace the missing MS2 sequences with those of fr or KU1. Rather, hybrids
      arose by attaching the complete 5' UTR of fr or KU1 to the 5' terminus of the
      defective MS2 phage. Several elements of the 5' UTR then occurred twice, one from
      KU1 (or fr) and the other from MS2. These redundant elements are in most cases
      deleted upon evolution of the hybrids. As a result, the 5' UTR of KU1 (or fr)
      then replaced that of MS2. It was earlier shown that this 5' UTR could assume two
      alternating structures that facilitated transient translation of the proximal
      maturation gene. Apparently, this timer function of the 5' UTR was exchangeable
      and could function independently of the rest of the genome. When hybrids were
      competed against wild-type, they were quickly outgrown, probably explaining their
      absence from natural isolates.

PMID- 11961279
TI  - Mutant prion protein acquires resistance to protease in mouse neuroblastoma
      cells.
AB  - Conversion of the cellular isoform of the prion protein (PrP(C)) into the
      pathogenic isoform (PrP(Sc)) is thought to be the causative event in prion
      diseases. Biochemically, PrP(Sc) differs from PrP(C) in its partial resistance to
      proteinase K (PK). The amino acid sequence AGAAAAGA, comprising residues 112-119
      of the murine PrP(C), has been shown to be amyloidogenic and evolutionarily
      conserved. To assess the effect of mutations at and around this hydrophobic
      sequence on protease resistance, the sequence was replaced either by alanines or
      by glycines and, in a third mutant, a large part surrounding this region was
      removed. The PrP mutant carrying substitutions of glycines for alanines showed PK
      resistance and aberrant proteolytic processing. Tetracycline-induced expression
      of this mutant indicated that resistance to protease is acquired concurrent with
      the synthesis of the protein. These findings indicate that mutations in the
      central hydrophobic region lead to immediate alterations in PrP structure and
      processing.

PMID- 11961280
TI  - New Zealand sheep with scrapie-susceptible PrP genotypes succumb to experimental
      challenge with a sheep-passaged scrapie isolate (SSBP/1).
AB  - Scrapie does not occur in New Zealand (NZ), although PrP gene alleles associated
      with susceptibility to the disease are found at relatively high frequencies in NZ
      sheep. The hypothesis that scrapie is a genetic disease of sheep is thus unlikely
      to be true. To confirm that NZ sheep are actually susceptible to scrapie
      infection, NZ sheep of various PrP genotypes were challenged by subcutaneous
      inoculation with a sheep-passaged scrapie isolate (SSBP/1). Showing similar PrP
      genetics to that seen in UK sheep, all NZ sheep carrying the VRQ PrP allele
      developed clinical signs typical of scrapie, with characteristic
      neurodegenerative changes and PrP(Sc) evident on histopathological examination of
      their brains and lymphoid tissues. The incubation periods recorded in NZ sheep
      were generally shorter than those found in UK sheep. The results confirm that New
      Zealand sheep are as susceptible as their UK counterparts to experimental scrapie
      infection by subcutaneous inoculation.

PMID- 11961281
TI  - Max Ferdinand Perutz 1914-2002.

PMID- 11961282
TI  - Local squaring functions.
AB  - Simple modifications to the Sayre squaring method determine a class of functional
      atomic form constraints representing the likelihood that a particular atomic form
      occupies a localized volume of the unit cell. The functional formulation, as
      opposed to the traditional structure-factor equation formulation, facilitates
      modeling multiple atom types and integrating atomic form information into
      established density-modification routines. Two complementary methods of phase
      refinement are considered. The first method constructs an atomic resolution
      probabilistic filter from the atomic form functions. The probabilistic filter is
      used to modify density throughout the unit cell, in both the solvent and
      macromolecular regions of the unit cell. The second method exploits the automated
      map interpretation aspects of the atomic form functions. A simple iterative phase
      refinement procedure alternating the two methods successively is applied to three
      small metalloproteins, with significant phase improvements beyond that obtained
      with conventional density modification or refinement in accordance with
      reciprocal-space squaring equations.

PMID- 11961283
TI  - The asymptotic leading term of anisotropic small-angle scattering intensities.
      II. Non-convex particles.
AB  - For anisotropic particulate samples with scattering contrast (delta n)(2), the
      leading asymptotic term of the scattering intensity, along a direction q (q/q) of
      reciprocal space, is [4 pi(2)(delta n)(2)/q(4)]sigmaj [1/kappaG.j(+/-q)]. Here,
      kappaG.j(+/-q)denotes the Gaussian curvature value at the points (labelled by j)
      of the interphase surface where the normal is either parallel or antiparallel to
      q. If the Gaussian curvature vanishes at, say, the jth of these points, the
      corresponding contribution takes the form Cj/qalpha with 2< or = alphaj<4, Cj and
      alphaj being determined by the local behaviour of the surface. However, the
      intensity detected by a counter pixel, with opening solid angle deltaomega(q0)
      along (mean) direction q0, asymptotically still behaves as 4pi(2) (delta
      n)(2)(deltaomega(q0))/q(4), where S(deltaomega(q0)) is the area of that part of
      the interface that has its normals inside deltaomega(q0).

PMID- 11961284
TI  - Wavefunctions derived from experiment. III. Topological analysis of crystal
      fragments.
AB  - A constrained wavefunction model has been used to extract a Hartree-Fock
      wavefunction for C2H2O4.4H2O from both low-angle (sin theta /lambda < 0.71 A-1,
      571 reflections) and full (sin theta / lambda < 1.00 A-1, 968 reflections)
      experimental X-ray diffraction data for crystalline alpha-oxalic acid dihydrate
      (alpha-C2H2O4.2H2O) using polarized double-zeta and triple-zeta Gaussian basis
      sets. Properties obtained from the zero-flux partitioning of the total charge
      density distribution derived from these wavefunctions, as well as from multipole
      refinement of the experimental data, are calculated and compared. This work
      represents the first calculation of integrated atomic properties derived from the
      fitting of Gaussian density functions to experimental X-ray diffraction data. In
      particular, atomic kinetic energies derived from experimental data are presented
      for the first time. The results obtained from the constrained (experimental)
      charge density show qualitatively similar properties to those obtained from
      conventional ab initio gas-phase calculations, though the quantitative
      differences are often substantial. The accuracy of integrated properties
      calculated using this procedure was established from the analysis of a
      wavefunction derived from simulated random-error diffraction data; that is, data
      obtained by adding normally distributed errors to the experimental structure
      factors. Analysis of this random-error wavefunction indicated that most
      topological properties are accurate to within approximately 5%, although the
      error is much larger for those properties that have a steep gradient in the
      region being evaluated [e.g. the value of V(2)rho(rb) at bond critical points] or
      are very small (e.g. the atomic dipole moment). Calculations of the constrained
      wavefunction using both the larger basis set and the complete set of experimental
      data yield results that agree quantitatively with the smaller calculations.

PMID- 11961285
TI  - Wavefunctions derived from experiment. IV. Investigation of the crystal
      environment of ammonia.
AB  - Constrained Hartree-Fock calculations have been performed to obtain wavefunctions
      that reproduce experimental X-ray structure-factor magnitudes for crystalline NH3
      to within the limits of experimental error. Different model densities using both
      a single molecule and clusters of NH3 in the calculation of X-ray structure
      factor magnitudes have been examined. The effects of the crystalline lattice on
      the experimental wavefunction of the NH3 unit can be reproducibly recovered. The
      construction of structure-factor magnitudes based on normally distributed random
      perturbations of the experimental values has also been used to gauge the accuracy
      of integrated atomic properties obtained from the wavefunctions, the point at
      which the constraint procedure should be terminated, and the approximate error in
      the experimental sigma(k) values.

PMID- 11961286
TI  - Three-beam X-ray diffraction in a semi-infinite perfect crystal.
AB  - The approach to multibeam X-ray diffraction by Shen [Acta Cryst. (1986). A42, 525
      533] has been carefully re-examined for three-beam Laue-Laue diffraction in a
      perfect non-absorbing semi-infinite crystal. A modified version of Shen's theory
      is shown to be equivalent to the Takagi-Taupin formalism. The perturbation of the
      two-beam integrated power when a third beam is being excited is thus expressed by
      non-diverging terms. Both Aufhellung and Umweganregung terms are recovered.

PMID- 11961287
TI  - Energy landscape paving for X-ray structure determination of organic molecules.
AB  - The efficiency of a recently proposed novel global optimization method, energy
      landscape paving (ELP), is evaluated with regard to the problem of crystal
      structure determination from simulated X-ray diffraction data comprising
      integrated diffraction intensities. The new approach has been tested using the
      example of 9-(methylamino)-1H-phenalen-1-one 1,4-dioxan-2-y1 hydroperoxide
      solvate (C14H11NO.C4H8O4). The results indicate that, for this example, ELP
      outperforms standard techniques such as simulated annealing.

PMID- 11961288
TI  - Ab initio determination of a crystal structure by means of the Schrodinger
      equation.
AB  - It is shown that the use of the Schrodinger equation may lead to the ab initio
      determination of the positions of the nuclei in a crystal, given a limited number
      of diffracted-beam intensities. In particular, it is shown that an extremely
      simplified Schrodinger equation in physical momentum space provides a
      sufficiently sound theoretical basis to develop an algorithm using diffraction
      data alone. This algorithm has been tested with a known 41 atom crystalline
      structure (not including hydrogen atoms) in space group P1. The extracted
      information is sufficient to determine the positions of all atoms. In addition,
      theoretical developments relevant to the connection between momentum space in
      quantum mechanics and diffraction theory have been formulated.

PMID- 11961289
TI  - Likelihood-based refinement. I. Irremovable model errors.
AB  - In conventional structure refinement, the discrepancy between the calculated
      magnitudes and those observed in X-ray experiments is attributed to errors
      inherent in preliminary assigned values of the model parameters. However, the
      chosen set of model parameters may not be adequate to describe the structure
      factors precisely. For example, if some atoms are not included in the current
      model, then the structure factors calculated from such a partial model contain
      'irremovable errors'. These errors cannot be eliminated by any choice of the
      parameters of the partial structure. Probabilistic modelling suggests a way to
      take irremovable errors into account. Every trial set of values of the model
      parameters is now associated with the joint probability distribution of the
      calculated magnitudes, rather than with a particular set of magnitudes. The new
      goal of the refinement is formulated as the search for the distribution that is
      the most consistent with the observed data. The statistical likelihood is a
      possible measure of the consistency. The suggested quadratic approximation of the
      likelihood function allows the likelihood-based refinement to be considered as a
      kind of least-squares refinement that uses appropriate weights and modified
      targets for the calculated magnitudes. This in turn enables the analysis of
      tendencies of the likelihood-based refinement in comparison with the classical
      least-squares refinement.

PMID- 11961290
TI  - Direct phasing by binary integer programming.
AB  - In the absence of phase information, a variety of electron-density distributions
      is consistent with the observed magnitudes. This ambiguity may be reduced
      significantly if the distribution values are restricted to 0 or 1, i.e. when the
      object of search is an envelope rather than a continuous electron-density
      distribution. The binarizing in both real (the grid-point density values) and
      reciprocal (the phases) spaces allows the usual structure-factor equations to be
      replaced by a system of linear inequalities with binary unknowns. A special
      computer procedure is applied to obtain several sets of values, which satisfy or
      almost satisfy these inequalities. The averaging of the found phase sets allows
      the final map to be calculated. The approach was tested with calculated and
      experimental data for a known protein structure. The size of the grid for the
      envelope calculation is at the moment the major limitation of the approach.
      Nevertheless, even for a very small grid, some structure information can be
      extracted and used as a starting point for further phase improvement or as a way
      to solve the molecular replacement problem.

PMID- 11961292
TI  - On the spectrum of fullerenes.
AB  - The most symmetrical C50 to C70 fullerenes with minimum numbers of pairs of
      adjacent pentagonal facets are considered in this paper. Like the well known C60
      (35m) and C70 (10m2) fullerenes with no adjacent pentagonal facets, they appear
      to be stable in physical experiments and cause the visible peaks in mass spectra
      of carbon clusters produced by laser vaporization of carbon.

PMID- 11961291
TI  - Diffraction by partially occupied helices.
AB  - An expression for cylindrically averaged intensity diffracted by a partially
      occupied helix (i.e. by a set of identical molecules bound to some, but not all,
      points of a discrete helix) is derived. The result is compared with previous
      studies and its application to muscle diffraction is discussed.

PMID- 11961294
TI  - Corrections to Crystallographic Groups of Four-Dimensional Space by Brown et al.
      (1978) [New York: Wiley and Sons].

PMID- 11961296
TI  - Three-dimensional approach to stem cell therapy.
AB  - Recent progress in stem cell research is opening a new hope for cell therapy in
      regenerative medicine. Two breakthroughs were made in the stem cell era, one, new
      discoveries in multi-potentiality of adult stem cells beyond the traditionally
      appreciated extent, and the other, establishment of pluripotent stem cell from
      human embryo. In addition to the newly identified multi-potentiality of adult
      stem cells, their ability to be trans-differentiated toward other tissue types
      (stem cell plasticity) as well as to migrate toward the site of tissue damage
      make adult stem cells particularly attractive choice for stem cell based therapy.
      Stem cell therapy for organ regeneration, therefore, could be approached from
      three distinct dimensions: first, direct differentiation of multi-potent stem
      cells toward desired tissue types; secondly, regeneration of specific tissues
      through in vivo stem cell plasticity, and lastly, by tissue-specific stem cells
      from many types of organs. While each approach in stem cell therapy poses
      distinctive limitations for their successful clinical applications, understanding
      regulatory mechanisms of stem cell self-renewal and their in vivo engraftment
      will mostly extend their medical efficacy of stem cell based therapy.

PMID- 11961297
TI  - Expression and regulation of endothelial nitric oxide synthase by vascular
      endothelial growth factor in ECV 304 cells.
AB  - Nitric oxide (NO) seems to play a pivotal role in the vascular endothelial growth
      factor (VEGF)-induced endothelial cell proliferation. This study was designed to
      investigate the role and intracellular signal pathway of endothelial nitric oxide
      synthase (eNOS) activation induced by VEGF. ECV 304 cells were treated with
      VEGF(165) and then cell proliferation, eNOS protein and mRNA expression levels
      were analyzed to elucidate the functional role of eNOS in cell proliferation
      induced by VEGF. After exposure of cells to VEGF(165), eNOS activity and cell
      growth were increased by approximately two-fold in the VEGF(165) -treated cells
      compared to the untreated cells. In addition, VEGF stimulated eNOS expression at
      both the mRNA and protein levels in a dose-dependent manner. Phosphatidylinositol
      3 kinase (PI-3K) inhibitors were used to assess PI-3K involvement in eNOS
      regulation. LY294002 was found to attenuate VEGF-stimulated eNOS expression.
      Wortmannin was not as effective as LY294002, but the reduction effect was
      detectable. Cells activated by VEGF showed increased ERK1/2 levels. Moreover, the
      VEGF-induced eNOS expression was reduced by the PD98059, MAPK pathway inhibitor.
      This suggests that eNOS expression might be regulated by PI-3K and the ERK1/2
      signaling pathway. In conclusion, VEGF(165) induces ECV 304 cell proliferation
      via the NO produced by eNOS. In addition, eNOS may be regulated by the PI-3K or
      mitogen-activated protein kinase pathway.

PMID- 11961298
TI  - Early Screening of oxacillin-resistant Staphylococcus aureus and Staphylococcus
      epidermidis from blood culture.
AB  - The timely detection of blood-borne pathogens is one of the most important
      functions of the microbiology laboratory. Recently, methicillin-resistant
      staphylococci have become the most important pathogens seen by the laboratory.
      The purpose of this study was to evaluate Staphy agar, a novel screening medium,
      for the detection methicillin-resistant Staphylococcus aureus, S. epidermidis, or
      other coagulase-negative staphylococci (CNS) from positive blood cultures showing
      Gram-positive cocci in clusters. Eighty-six blood cultures that yielded Gram
      positive cocci in clusters were included in this study. The organisms were
      finally identified by the Vitek system, and oxacillin resistance was confirmed by
      polymerase chain reaction (PCR)-based mecA gene detection. The identification and
      oxacillin resistance of all S. aureus strains showed complete agreement with the
      Vitek and PCR results. The presumptive detection of S. epidermidis and other CNS
      were consistent with the Vitek system in 94.7%, and the screening of oxacillin
      resistance was consistent with the result of PCR in 92.1% of 38 strains. The
      Staphy agar method is reliable and rapid for differentiating Gram-positive cocci
      in clusters in blood and for determining their methicillin resistance.

PMID- 11961299
TI  - Mantle cell lymphoma, blastoid variant, diagnosed on the basis of cytomorphology
      and flow cytometric immunophenotyping of the lymph node aspirate and peripheral
      blood.
AB  - Mantle cell lymphoma, blastoid variant (B-MCL), is a very rare type of non
      Hodgkin's lymphoma exhibiting an aggressive clinical course. We describe a case
      of B-MCL showing generalized lymphadenopathy and leukemic conversion in a 62-yr
      old man. The case was diagnosed and subclassified as B-MCL on the basis of cyto
      morphology and immunophenotype. Microscopic examination of the peripheral blood
      (PB) showed a spectrum of cells ranging from small mature lymphocytes to medium-
      and large-sized lymphocytes with blast-like chromatin and prominent nucleoli. The
      lymphoma cells were monoclonal B cells with moderately intense surface IgM. They
      were CD5 positive, cyclin D1 positive, CD10 negative, and CD23 negative. The flow
      cytometric immunophenotyping and DNA ploidy analysis of the PB and material
      obtained by aspiration cytology supported the diagnosis of B-MCL. These findings
      underline the utility of aspiration cytology in diagnosing B-MCL when
      cytomorphologic examination is combined with flow cytometric analysis of immuno
      phenotype and demonstration of proliferation markers.

PMID- 11961300
TI  - Bronchiolitis obliterans organizing pneumonia: clinicopathologic review of a
      series of 45 Korean patients including rapidly progressive form.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathological
      syndrome associated with a variety of disease entities. The aim of this study was
      to review cases with initial diagnosis of BOOP applying uniform histopathologic
      criteria, and analyze the clinical characteristics of proven cases of BOOP
      including rapidly progressive form. A total of 81 cases, initially diagnosed as
      BOOP and with available tissue sections, was collected. Thirty six cases (44.4%)
      were excluded from the study, more than two thirds of which were given a revised
      diagnosis of interstitial pneumonitis/fibrosis other than BOOP. Thirty one
      patients were classified as idiopathic BOOP, 8 patients as secondary BOOP, and 6
      patients as rapidly progressive BOOP. Open lung biopsy specimen from all six
      cases with lethal outcome showed more severe interstitial inflammation and septal
      fibrosis and/or alveolar exudate with a varying degree than those with good
      prognosis. There was no difference by the sexes. The two most frequent presenting
      symptoms were cough and dyspnea. Bilateral multifocal consolidation was a common
      radiological finding. More than 70% cases of idiopathic BOOP experienced clinical
      improvements. The diagnosis of BOOP is usually suggested by clinicoradiologic
      findings, but needs to be confirmed histopathologically, preferably through
      surgical open or video-assisted thoracoscopic biopsy.

PMID- 11961301
TI  - Risk factors for hepatitis C virus infection among Koreans according to the
      hepatitis C virus genotype.
AB  - To investigate risk factors for HCV infection according to the genotype, we
      studied 178 patients positive for HCV-PCR and 226 controls that were negative for
      the anti-HCV antibody. One hundred and twenty five controls (community control)
      were recruited from spouses of HCV-PCR-positive patients and the other 101 from
      hospital visitors (hospital control). HCV genotyping was performed by PCR, and
      epidemiological data were obtained from all participants. The distribution of HCV
      genotypes was as follows -- 1a (0.6%), 1b (39.9%), 2a (38.2%), 2b (0%), 3 (1.1%),
      and unclassified (20.2%). By multivariate analysis, blood transfusion (OR 2.90)
      and endoscopy (OR 2.80) were found to be risk factors for HCV genotype 1b versus
      the community control. Similarly, blood transfusion (OR 3.17) was found to be
      risk factors for HCV genotype 1b versus the hospital control. Blood transfusion
      (OR 2.75) and endoscopy (OR 3.57) were risk factors for HCV genotype 2a versus
      the community control, and blood transfusion (OR 4.55) and endoscopy (OR 2.16)
      were those versus the hospital control. Our results suggest that the risk factors
      for HCV infection are similar among the different genotypes. Blood transfusion
      and endoscopy were found to be associated with HCV infection.

PMID- 11961302
TI  - NF-kappa B binding activity and cyclooxygenase-2 expression in persistent CCl(4)
      treated rat liver injury.
AB  - The involvement of NF-kappa B binding activity is known to be important in the
      mechanism of acute liver injury and in the induction of cyclooxygenase (COX-2).
      This study was performed to evaluate NF-kappa B binding activity and the
      expression of COX-2 in chronic liver injury induced by carbon tetrachloride
      (CCl(4)). Liver tissues from Sprague-Dawley rats were collected at 1, 3, 5, and
      7th week after intraperitoneal injection of 0.1 mL of CCl(4)/100 g body weight
      twice a week. Reactive oxy-gen species (ROS) were measured in the
      postmitochondrial fraction by dichlorofluorescein formation with a fluorescent
      probe. An electrophoretic mobility shift assay was performed for NF-kappa B
      binding activity. Western blot was performed to measure the level of COX-1, COX
      2, p65, p50, and I B proteins. ROS and NF-kappa B activity increased during the
      CCl4-induced chronic liver injury. The expression of nuclear p65 protein and p50
      protein increased compared with that of the control, while the cytoplasmic I B
      protein decreased as the inflammation persisted. The expression of COX-2 in
      CCl(4)-treated rat liver increased compared with that of the control. It could be
      suggested that ROS produced by CCl(4) treatment increased NF-kappa B binding
      activity and thereby COX-2 expression, and these might be implicated in the
      progress of chronic liver damage.

PMID- 11961303
TI  - Clinical prognostic values of vascular endothelial growth factor, microvessel
      density,and p53 expression in esophageal carcinomas.
AB  - Vascular endothelial growth factor (VEGF) is known to play a key role in tumor
      angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF. We
      investigated the effect of VEGF on esophageal carcinoma and the correlation
      between VEGF and p53. Tissue samples were taken from 81 patients with esophageal
      carcinoma after surgery. VEGF and p53 expressions were examined by
      immunohistochemical staining. Microvessels in the tumor stained for CD34 antigen
      were also counted. VEGF and p53 expressions were observed in 51.3% (41/80) and
      51.9% (41/79), respectively. The microvessel density was 70.9+/-6.7 (mean+/-SE)
      in VEGF-positive group and 68.7+/-5.1 in VEGF-negative group. However, no
      correlation was noted between VEGF and p53 expression. Whereas the tumor size,
      nodal status, depth of invasions, and tumor stage were associated with poor
      overall survival, VEGF expression or p53 expression was not. These results
      indicate that VEGF and p53 are highly expressed in esophageal carcinomas. Since
      the VEGF expression is not correlated with the p53 expression, microvessel
      density or clinicopathological findings, further studies with other angiogenic
      molecules are needed to determine the role in esophageal carcinomas.

PMID- 11961304
TI  - Effects of high glucose on interleukin-6 production in human mesangial cells.
AB  - Interleukin (IL)-6 is an autocrine growth factor for mesangial cells. It is not
      known whether high glucose influences IL-6 production in mesangial cells.
      Angiotensin II (AGII) is involved in the progression of renal diseases including
      diabetic nephropathy. Therefore, we evaluated the effects of high glucose in
      concert with AGII on IL-6 production in human mesangial cells and the modulation
      by blocking AGII. After 48 hr of culture, IL-6 mRNA expression was analyzed by
      reverse transcription and polymerase chain reaction (PCR). Quantitative
      determination of IL-6 concentrations in the culture supernatants of mesangial
      cells was performed using a sandwich enzyme immunoassay kit. Incubation of
      mesangial cells with high glucose (450 mg/dL) reduced the ratio of PCR products
      for IL-6 to beta-actin on densitometric results, while AGII (10(-7)M) increased
      it. The IL-6 secretion in the supernatant was also increased by AGII and
      decreased by high glucose. The IL-6 mRNA expression and IL-6 secretion in
      combination of high glucose and AGII were higher than those in high glucose and
      similar with those in control media. The addition of losartan (10(-6)M) or
      captopril (10(-6)M) to high glucose had no additional effects on IL-6 production.
      These results suggest that whereas AGII increases IL-6 production, high glucose
      decreases it. The IL-6 production of mesangial cells in diabetic milieu may be
      complicated and depend on the local effects of high glucose and/or AGII.

PMID- 11961305
TI  - Differential expressions of Fas and Fas ligand in human placenta.
AB  - To investigate the expressions of Fas and Fas ligand (FasL) in human placenta, we
      studied the expressions of Fas and FasL in placenta with RT-PCR, immunoblotting
      and immunostaining. We observed amplified products of Fas and FasL transcripts,
      the band of Fas (52 kDa) and multiple bands of FasL (42-52 kDa) in placenta. Fas
      and FasL localized mainly on fetal vessels and on syncytiotrophoblasts
      respectively. The differential distribution of Fas and FasL in human placenta may
      reflect intrinsic expressions of them by trophoblasts during differentiation. The
      increased expression of Fas in trophoblasts may promote apoptosis of placenta in
      pathologic condition such as preeclampsia.

PMID- 11961307
TI  - Validation of a Korean version of the Fibromyalgia Impact Questionnaire.
AB  - The aim of this study was to translate the Fibromyalgia Impact Questionnaire
      (FIQ) into Korean and to evaluate its reliability and validity for use with
      Korean-speaking patients with fibromyalgia (FM). After translating the FIQ into
      Korean, we administered it to 55 patients with FM (28 patients filled out the
      questionnaire again 7 days later) together with a Korean version of the Health
      Assessment Questionnaire (HAQ) and the Symptom Checklist-90-Revision (SCL-90-R).
      The tender-point count (TPC) was calculated from tender points identified by
      thumb palpation. In addition to sociodemographic characteristics, the severity of
      relevant current clinical symptoms, e.g., pain intensity, fatigue, and morning
      stiffness, were assessed by 10-cm visual analog scales (VAS). The test-retest
      reliability was between 0.466 and 0.780 (total 0.778). Cronbach's alpha was 0.800
      for FIQ1 (the first assessment) and 0.857 for FIQ2 (the second assessment),
      indicating acceptable levels of internal consistency for both assessments.
      Significant correlations were obtained between the FIQ items, the HAQ, the
      severity of clinical symptoms, and the subscales of the SCL-90-R. In conclusion,
      the Korean version of the FIQ is a reliable and valid instrument for measuring
      health status and physical functioning in Korean patients with FM.

PMID- 11961306
TI  - Vero cell co-culture counteracts the detrimental effects of hydrosalpinx fluid on
      the development of mouse embryos in vitro.
AB  - Recent studies have suggested that the hydrosalpinx has a negative effect on
      pregnancy outcome, with markedly diminished implantation and increased early
      pregnancy loss. Fluid from the hydrosalpinx may leak into and accumulate in the
      uterine cavity. It is not clear, however if this creates a hostile local
      environment in the uterus for embryo implantation or exerts a direct embryotoxic
      effect. This study was conducted to investigate the detrimental effects of
      hydrosalpinx fluid (HSF) on the development of mouse embryos in vitro and to
      demonstrate whether Vero cells overcome these adverse effects. HSF was collected
      from three women with bilateral hydrosalpinx at the time of laparoscopic surgery.
      Collected fluid was centrifuged and the supernatant was frozen at -20 degrees C.
      For co-culture, Vero cells were commercially obtained in a frozen state and
      cultured using Ham's F10 medium. Single-cell mouse embryos (B6CBAF1) were
      cultured for 5 days in 0, 0.4, 0.8, and 1.2% of HSF in media with and without
      Vero cells and examined daily to record the number of embryos reaching expanded
      blastocyst and hatching stage. Co-culture of mouse embryos with Vero cells at
      0.8% HSF concentration significantly enhanced embryo development, but not at 1.2%
      hydrosalpinx fluid concentration. These results suggest that HSF is highly
      embryotoxic and Vero cells are likely to overcome these detrimental effects to
      some degree.

PMID- 11961308
TI  - The effect of intrathecal gabapentin on mechanical and thermal hyperalgesia in
      neuropathic rats induced by spinal nerve ligation.
AB  - Gabapentin decreases the level of glutamate and elevates that of alpha-amino
      butyric acid in the central nervous system. Gabapentin was shown to have
      antinociceptive effects in several facilitated pain models. Intrathecal
      gabapentin was also known to be effective in reducing mechanical allodynia in
      animals with neuropathic pain. In this study, we investigated to see whether
      intrathecal gabapentin produces antihyperalgesic effects on thermal and
      mechanical hyperalgesia in neuropathic rats and whether its effects are
      associated with motor impairment. To induce neuropathic pain in Sprague-Dawley
      rats, left L5 and L6 spinal nerves were ligated. After a week, lumbar
      catheterization into subarachnoid space was performed. Then, paw withdrawal times
      to thermal stimuli and vocalization thresholds to paw pressure were determined
      before and up to 2 hr after intrathecal injection of gabapentin. Also, motor
      functions including performance times on rota-rod were determined. Intrathecal
      gabapentin attenuated significantly thermal and mechanical hyperalgesia in
      neuropathic rats, but did not block thermal and mechanical nociception in sham
      operated rats. Intrathecal gabapentin of antihyperalgesic doses inhibited motor
      coordination performance without evident ambulatory dysfunction. This study
      demonstrates that intrathecal gabapentin is effective against thermal and
      mechanical hyperalgesia, in spite of moderate impairment of motor coordination.

PMID- 11961309
TI  - Ultrastructural characteristics of the round window membrane during pneumococcal
      otitis media in rat.
AB  - To understand better the pathogenesis of inner ear (IE) damage caused by otitis
      media (OM), the round window membrane(RWM) structure was investigated in a rat
      model for pneumococcal otitis media (POM). The RWM of 25 rats were evaluated
      light and electron microscopically on 1 day, 3 days, 6 days, 10 days, and 20 days
      after the unilateral inoculation of type 3 pneumococcus suspension into their
      middle ear cavities. The thickness of the RWM increased in various stages of the
      pneumococcus-evoked otitis media, compared with that of the normal. The
      thickening was most pronounced on day 1, being about 4 to 5 times greater than
      that of the normal RWM. All layers of the RWM were affected by the pneumococcal
      infection, but the major changes were confined to the subepithelial space close
      to the basement membrane (BM). Together with alterations to the BM, the most
      distinct pathological features were characterized by an increase and hypertrophy
      of fibroblasts in association with abundant collagen fibers. Elastic fibers
      observed close to the inner mesothelial layer under a high power magnification
      also increased during the experiment. These results will be relevant to a better
      understanding of the histologic implication of RWM in stages of acute otitis
      media involving pneumococcus-evoked otitis media.

PMID- 11961310
TI  - Comorbid mental disorders among the patients with alcohol abuse and dependence in
      Korea.
AB  - This study investigated the patterns of alcohol disorder comorbidity with other
      psychiatric disorders, using Korean nationwide epidemiological data. By two-stage
      cluster sampling, 5,176 adult household residents of Korea were interviewed using
      the Korean version of the Diagnostic Interview Schedule. Psychiatric disorders
      strongly associated with alcohol disorders were, other drug abuse or dependence,
      major depression, simple phobia, antisocial personality disorder, tobacco
      dependence, and pathological gambling. Male alcoholics had a tendency to begin
      with tobacco dependence, and some male pathological gamblers first had alcohol
      disorders. The presence of comorbid psychiatric disorders was associated with a
      more severe form and the later onset of alcohol disorders, and associated with
      help-seeking for alcohol abuse/dependence.

PMID- 11961311
TI  - Expression of TNF-alpha and TGF-beta 1 in the rat brain after a single high-dose
      irradiation.
AB  - Cytokines and growth factors are important regulatory proteins controlling the
      growth and differentiation of normal and malignant glial cells. In this study, we
      investigated the expression and origin of tumor necrosis factor-alpha (TNF-alpha)
      and transforming growth factor-beta 1 (TGF-beta 1) in the subacute brain injury
      after a single high-dose irradiation using 60 Sprague-Dawley rats. The right
      cerebral hemispheres of rats were exposed to a single 10 Gy dose of gamma rays
      using Ir-192. The radiation effect was assessed at 1 week, 2 weeks, 4 weeks, 6
      weeks, and 8 weeks after irradiation, and the results were compared with those in
      sham operation group. Histological changes characteristic of radiation injury
      were correlated with the duration after the single dose irradiation. The loss of
      cortical thickness also increased with the lapse of time after irradiation. The
      TNF-alpha expression in the irradiated cerebral hemispheres was significantly
      increased compared with that in the sham operation group. TGF-beta 1 expression
      was also increased in the irradiated hemispheres. Immunohistochemical study
      revealed that TGF-beta 1 was expressed predominantly by infiltrating macrophages
      and astrocytes around the necrotic areas. These findings indicate that TNF-alpha
      and TGF-beta 1 may play prominent roles in the radiation injuries after a single
      high-dose irradiation.

PMID- 11961312
TI  - No association of factor XIII Val34Leu polymorphism with primary intracerebral
      hemorrhage and healthy controls in Korean population.
AB  - The polymorphism in the factor XIII A-subunit gene (FXIII Val34Leu) has been
      recognized as a risk factor for primary intracerebral hemorrhage (PICH). In
      addition, FXIII Val34Leu has a significant ethnic heterogeneity. FXIII Val34Leu
      was detected in 41.7-54.8% of the Westerners, but in 2.5% of the Asians. We aimed
      to evaluate the prevalence of FXIII Val34Leu in patients with PICH and in healthy
      controls among Koreans. We recruited 58 in-patients with PICH, defined by brain
      computed tomography or magnetic resonance imaging, and 48 controls matched for
      age, sex, and risk factors for cerebrovascular diseases. Genomic DNA was
      extracted from blood. A 183-bp fragment of exon 2/intron B of the factor XIII
      Asubunit gene was amplified by polymerase chain reaction (PCR). The factor XIII
      genotype was determined through a single-stranded conformational polymorphism.
      Fifty-eight patients and 48 controls showed the same band patterns on SSCP. In
      addition, we directly sequenced six random-selected DNA segments using DNA auto
      sequencer. In conclusion, the results of this study suggest that FXIII Val34Leu
      be absent or rare both in patients with PICH and in healthy controls among
      Koreans.

PMID- 11961314
TI  - A case of maternal tetanus in Korea.
AB  - Tetanus is uncommon in Korea due to the introduction of vaccination programs and
      advances in public health. A case of maternal tetanus occurred on the 9 day
      postpartum in a 29-yr-old woman, who had not received a 10-yr-booster of tetanus
      diphtheria toxoid after receiving the primary series of tetanus-toxoid-containing
      vaccine. There has hitherto been no reports on maternal tetanus in Korea. This
      case illustrates that tetanus remains a medical problem, principally among non-
      and under-immunized adults. The only way to fully prevent this disease is to
      ensure adequate immunization in all adults.

PMID- 11961313
TI  - Outcome of postoperative intratumoral bleomycin injection for cystic
      craniopharyngioma.
AB  - Total excision is a treatment of choice in preventing the relapse of
      craniopharyngioma, but for tumors involving an extensive area, it is often
      associated with an increased risk of complications. We have performed a partial
      or subtotal tumor removal followed by repeated injection of bleomycin into the
      remaining tumor through a subcutaneous reservoir as postoperative adjuvant
      therapy. A retrospective review of clinical, radiological, and surgical data was
      performed for 10 patients (5 males and 5 females; age, 3-65 yr; follow-up
      duration, 12-79 months) with cystic craniopharyngiomas. The measurements of
      lactate dehydrogenase (LDH) level at each aspiration were performed. The
      shrinkage and/or stabilization of tumor was initially noted in all cases. The
      recurrence of tumor was seen in 4 cases (40%). The decreased or increased level
      of LDH was interpreted as tumor shrinkage or recurrence, respectively. The
      transient toxic reactions were observed in 3 patients (30%). Our study
      demonstrates that postoperative bleo-mycin injection for cystic
      craniopharyngioma, although does not appear to eradicate the tumor, decreases and
      stabilizes the tumor size, when used as an adjuvant therapy in young patients.

PMID- 11961315
TI  - Two episodes of Stenotrophomonas maltophilia endocarditis of prosthetic mitral
      valve: report of a case and review of the literature.
AB  - Stenotrophomonas maltophilia (previously named Xanthomonas maltophilia) is an
      aerobic, non-fermentive, Gram-negative bacillus that is wide spread in the
      environment. It was considered to be an organism with limited pathogenic
      potential, which was rarely capable of causing diseases in human other than those
      who were in debilitated or immunocompromised state. More recent studies have
      established that Stenotrophomonas maltophilia can behave as a true pathogen.
      Endocarditis due to this organism is rare, and only 24 cases of Stenotrophomonas
      maltophilia endocarditis have been reported in the medical literature. Most cases
      were associated with risk factors, including intravenous drug abuse, dental
      treatment, infected intravenous devices, and previous cardiac surgery. We present
      a case with two episodes of Stenotrophomonas maltophilia endocarditis after
      mitral valve prosthesis implantation, which was treated with antibiotics
      initially, and a combination of antibiotics and surgery later. To our knowledge,
      this is the first case of repetitive endocarditis due to Stenotrophomonas
      maltophilia.

PMID- 11961316
TI  - Aortoesophageal fistula associated with tuberculous mediastinitis, mimicking
      esophageal Dieulafoy's disease.
AB  - Aortoesophageal fistula is a rare and lethal disorder that may result from
      primary diseases of aorta or esophagus, aortic bypass graft, ingestion of foreign
      body, trauma, surgical procedure or instrumentation. Tuberculous fistula is
      extremely rare. We present a 27-yr-old female patient with aortoesophageal
      fistula associated with tuberculous mediastinitis. The patient experienced
      massive hematemesis and esophagoscopy revealed a small mucosal defect with
      exudate-coated blood vessel like Dieulafoy 's lesion on about 25 cm from the
      incisor teeth. Despite two sessions of endoscopic hemostatic procedures, active
      massive hemorrhage recurred and was controlled effectively with a prompt
      insertion of Sengstaken-Blakemore tube. The patient underwent open thoracotomy,
      which revealed aortoesophageal fistula. Numerous white-yellowish, millet seed
      like tubercles were scattered in pleural and abdominal cavity. Division of
      fistular tract and esophageal resection with Ivor-Lewis anastomosis were
      performed. Histopathologic study confirmed tuberculous pleuritis and peritonitis.
      The patient died of postoperative pulmonary complication.

PMID- 11961317
TI  - Successful treatment of progressive rheumatoid interstitial lung disease with
      cyclosporine: a case report.
AB  - Treatment of interstitial lung disease (ILD) in rheumatoid arthritis (RA) has
      been controversial. Although there have been several anecdotal reports on the
      efficacies of corticosteroids or cytotoxic agents such as methotrexate,
      cyclophosphamide, azathioprine, and D-penicillamine for the treatment of ILD
      associated with RA, no controlled studies have been performed. To date,
      corticosteroids have been a central agent for the treatment of this disease, but
      their effects are partial and temporary in most cases. In addition, the adverse
      effects of these agents are considerable. On the other hand, limited information
      is available on the cyclosporine use in ILD associated with RA. We describe a 49
      yr old female patient with RA and ILD that had initially responded to high dose
      prednisolone and cyclophosphamide intravenous pulse therapy, and the lung disease
      was aggravated with the tapering of prednisolone. After 10 months of follow-up
      loss, the patient was successfully treated with low dose cyclosporine without
      high dose corticosteroids.

PMID- 11961318
TI  - Old abdominal pregnancy presenting as an ovarian neoplasm.
AB  - Abdominal pregnancy is extremely rare, but even more unusual is the prolonged
      retention of an advanced abdominal pregnancy with lithopedion formation. The
      presentation of lithopedion as an ovarian tumor without a symptom has not been
      reported in Korea. A 63-yr-old, gravida 2, para 1, woman was referred to us with
      an abdominal mass. Pelvic examination revealed normal postmenopausal uterus and a
      fetal head-sized movable hard mass in the lower abdomen. The computed tomographic
      scan showed a densely echogenic mass of 10-cm in diameter as an ovarian neoplasm.
      Laparotomy disclosed a lithopedion, of which the bones and cartilages were well
      preserved. There have been controversies on the treatment of lithopedion.
      Although some cases are stable for a long time, the morbidity increases when the
      operation is performed in an elderly patient. So we believe that the surgical
      intervention should be done as soon as possible after thorough consideration of
      the morbidity and the risk.

PMID- 11961319
TI  - Extraskeletal chondroma of the fallopian tube.
AB  - Extraskeletal chondroma can occur in the hands, feet, head and neck. This tumor
      usually presents as a small solitary nodule. The histogenesis of the tumor is
      controversial, but some have suggested a metaplastic origin. Chondroma of the
      fallopian tube is very rare. There is only one report in English literature. The
      origin of this tumor can be subcoelomic mesenchyme of the tubal serosa or
      mesenchyme of the myosalpinx. We describe a case of chondroma arising from the
      serosal surface of the fallopian tube with a review of literature. A 30-yr-old
      woman visited hospital due to left adnexal mass. On operating finding, 2 x 3 cm
      sized nodular mass was noted on the left tubal serosal area. The excised mass
      showed multilobulated appearance covered with thin fibrous membrane. The cut
      surface was solid, grayish yellow, and myxoid with a focal gelatinous area. The
      microscopic finding showed islands and elongated lobules of mature benign
      cartilage without cytologic atypia.

PMID- 11961320
TI  - Reactive cutaneous cytophagocytosis in nocardiosis.
AB  - Cutaneous nocardiosis, which usually manifests in the form of pustules,
      abscesses, or subcutaneous nodules, is occasionally found in immunocompromised
      patients. A 59-yr-old Korean man with myasthenia gravis and thymoma developed
      nodular skin lesions on his trunk. Histopathologically, abscess formation with a
      dense infiltrate of neutrophils and many cytophagic histiocytes were observed.
      Numerous filamentous organisms, which turned out to be Nocardia asteroides by
      culture, were also found. After sulfamethoxazole-trimethoprim therapy, all of the
      skin lesions rapidly decreased in size, with a marked diminution of the number of
      cytophagic histiocytes, and cleared up within four months. On reporting a case of
      cutaneous nocardiosis showing unusual histopathologic findings, we considered
      that reactive conditions should be included in the differential diagnosis of the
      cutaneous cytophagocytosis, and that nocardiosis could be one of the diseases
      showing reactive cytophagocytosis.

PMID- 11961321
TI  - Leber's hereditary optic neuropathy with 3460 mitochondrial DNA mutation.
AB  - Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease
      causing acute or subacute, bilateral optic atrophy mainly in young men. It is
      found to be a mitochondrial disorder with the primary mitochondrial DNA (mtDNA)
      mutations at 11,778, 3460, and 14,484. The incidence of each mutation is reported
      to be race-dependent. Point mutations at mtDNA nucleotide position 11,778 and
      14,484 have been reported in Korean patients with LHON, however there has been no
      report of mtDNA mutation at nucleotide position 3460. Molecular genetic analyses
      at four primary sites (11,778, 14,484, 15,257, and 3460) of mitochondrial DNA
      using the polymerase chain reaction, restriction enzyme digestion, and direct
      sequencing were performed in a 35-yr-old man with severe visual loss. A point
      mutation in the mtDNA at nucleotide position 3460 was identified and a conversion
      of a single alanine to a threonine was confirmed. To our knowledge, this is the
      first report confirming mtDNA mutation at nucleotide position 3460 in Korean
      patients with LHON. Detailed molecular analyses would be very helpful for the
      correct diagnosis of optic neuropathy of unknown etiology and for genetic
      counseling.

PMID- 11961322
TI  - Metachronous germinoma after total removal of mature teratoma in the third
      ventricle: a case report.
AB  - A rare case of intraventricular germinoma in the third ventricle, which occurred
      30 months after total removal of mature teratoma on the same location in a 29- yr
      old man is presented. Recurrence is supposed to represent an acceleration of
      localized dysplastic processes of totipotent germ cells present in the midline
      neuraxis or a growth of unidentified microscopic residue of germinoma component
      in mature teratoma. Although the radiation therapy after total removal of mature
      teratoma is still controversial, careful follow-up is warranted for evaluating a
      possible recurrence of other germ cell tumors.

PMID- 11961323
TI  - In vivo repeatability and reproducibility of the quantitative light-induced
      fluorescence method.
AB  - In vivo repeatability and reproducibility of the quantitative light-induced
      fluorescence (QLF) method were tested with respect to three variables: lesion
      area, and average and maximum changes in lesion fluorescence. To test the image
      capturing stages, three analysts each captured images of 15 incipient smooth
      surface lesions in vivo, and the images were analysed by one of the analysts. To
      test the analytical stage of the method, three analysts analysed the images of 15
      in vivo incipient smooth surface lesions. For the image-capturing stage, inter
      examiner reliability showed an intra-class correlation coefficient (r) between
      0.95 and 0.98. For the analytical stage, intra-examiner reliability for all three
      analysts showed a value of r between 0.93 and 0.99. Inter-examiner reliability
      showed a value of r between 0.95 and 0.99. It was concluded that the in vivo
      repeatability and reproducibility of the QLF method are excellent.

PMID- 11961324
TI  - A Monte Carlo simulation of the influence of sound enamel scattering coefficient
      on lesion visibility in light-induced fluorescence.
AB  - Quantitative light-induced fluorescence (QLF) is based on the dark appearance of
      a white spot in otherwise highly fluorescent enamel. This can be explained by the
      increased scattering coefficient in the white spot compared with that of sound
      enamel. The aim of this study was to estimate the effect of different sound
      enamel scattering coefficients (s(SE)) and enamel thickness d, caused by
      developmental enamel differences, on the fluorescence appearance of white-spot
      lesions. We ran a Monte Carlo simulation of a 4 x 4 mm(2) illuminated enamel slab
      on a highly fluorescent background. The slab had a 0.7 x 0.7 mm(2), 100-microm
      deep, white spot in the center. Fluorescent and back-scattered photons re-emitted
      from the central 2 x 2 mm(2) were recorded. We found that the fluorescence photon
      excitance from the white spot (F(WS)) was less than that of sound enamel (F(SE)),
      with an optimum difference for S(SE) between 20 and 80/mm. For s(SE) <20/mm, both
      F(SE) and F(WS) decreased with d. We found no relation with d for s(SE) >20/mm.
      The results indicate that for small s(SE), we are suffering from edge losses,
      which explains why the optimum for lesion visibility is not found at s(SE) =
      0/mm, as would be expected.

PMID- 11961325
TI  - Validity and reproducibility of a laser fluorescence system for detecting the
      activity of white-spot lesions on free smooth surfaces in vivo.
AB  - The aim of the study was to determine the reproducibility and validity of
      DIAGNOdent in detecting active and arrested caries lesions on free smooth
      surfaces. Volunteers were selected from state schools of Piracicaba, Sao Paulo,
      Brazil. Overall, 220 lesions were clinically examined. Two specially trained
      ('calibrated') examiners performed both clinical and laser evaluations
      independently, and after a 1-week interval, the examinations were repeated. The
      intra-examiner agreement for the laser evaluation was substantial (kappa(ex1) =
      0.79, kappa(ex2) = 0.71). There was almost perfect agreement between the two
      examiners for the clinical examination (kappa(ex1) = 0.95, kappa(ex2) = 0.85).
      The inter-examiner agreement showed substantial reproducibility (kappa = 0.77)
      for the laser examination and almost perfect agreement (kappa = 0.85) for the
      clinical evaluation. The validation criterion was the clinical examination of
      white spots, recorded as active or arrested. The sensitivity was 0.72 and the
      specificity was 0.73, which indicates that the DIAGNOdent was a good auxiliary
      method for detecting incipient caries lesions on free smooth surfaces. The
      utilization of both methods can improve the efficacy of caries diagnosis.

PMID- 11961326
TI  - Light-induced fluorescence studies on dehydration of incipient enamel lesions.
AB  - Changes in the hydration state of enamel affect its optical qualities, such as
      light scattering and fluorescence. In this study, the rate of fluorescence loss
      was measured when incipient enamel lesions with different de-remineralization
      history were left to dehydrate. Four groups of lesions were studied. In groups A,
      B and C, the lesions were prepared in vitro in an acid-gel system. Group A was
      kept as control, and groups B and C were remineralized (4 weeks) without and with
      1 ppm F in solution, respectively. Group D consisted of natural incipient
      lesions. Enamel fluorescence was measured for all lesions immediately after
      removal from water and subsequently at short intervals for 30 min. The change in
      fluorescence with dehydration varied between the groups. In lesions from groups A
      and B, it followed a double exponential decrease, while in lesions from groups C
      and D, it followed a mono-exponential decrease. In all groups, the fluorescence
      of sound surfaces declined mono-exponentially. The 'fractional fluorescence
      difference', defined as (L(sound) - L(carious) )/L(sound), became constant after
      periods of dehydration of about 5, 5, 20 and 5 min for groups A to D,
      respectively. The observation of the change of fluorescence with dehydration
      should be taken into consideration when planning studies that use fluorescence as
      an assessment method. However, it might also be used to gain insight into the
      properties for fluid transport inside the various lesions, relevant to de
      remineralization or fluoride treatments.

PMID- 11961327
TI  - Caries incidence in young type 1 diabetes mellitus patients in relation to
      metabolic control and caries-associated risk factors.
AB  - The aim of this study was to evaluate the caries incidence in a group of young
      patients with type 1 diabetes mellitus over a 3-year period from the onset of the
      disease in relation to metabolic control and to caries-associated risk factors.
      Sixty-four children and adolescents (8-15 years of age) had their diabetes
      treated and monitored according to a standard medical protocol and received
      extensive preventive oral health care based on individual needs. Data on blood
      glucose and glycosylated haemoglobin (Hb A(Ic)) were collected from the medical
      records. Whole saliva was collected every 3rd month and secretion rate, buffer
      capacity, glucose concentration, mutans streptococci and lactobacilli counts were
      determined. Dental examinations, including radiographs, were carried out once a
      year. Patients with less good metabolic control (>8.0% Hb A(Ic)) exhibited higher
      glucose levels in resting saliva (p < 0.05) and a significantly higher caries
      incidence (p < 0.05) compared to those with good metabolic control. The most
      influential determinants for high caries development during the 3-year follow-up
      period were metabolic control (odds ratio, OR = 5.7), poor oral hygiene (OR =
      6.5), previous caries experience (OR = 5.3) and high levels of salivary
      lactobacilli (OR = 5.0). The findings suggest that the level of metabolic control
      and traditional caries risk markers are important factors for caries development
      in children and adolescents with type 1 diabetes mellitus.

PMID- 11961328
TI  - Effect of a triclosan-containing toothpaste supplemented with 10% xylitol on
      mutans streptococci in saliva and dental plaque. A 6-month clinical study.
AB  - The aim of the present investigation was to evaluate the effect of the
      combination of triclosan and xylitol in toothpaste on mutans streptococci (MS) in
      saliva and dental plaque. 155 individuals with >10(5) MS/ml saliva were included
      in a 6-month double-blind clinical study. They were divided into three groups (n
      = 51-52) balanced according to their MS counts at baseline. Each group used one
      of the following types of dentifrice: (1) Colgate Total with the addition of 10%
      xylitol (Total-Xylitol), (2) Colgate Total and (3) Colgate Total without
      triclosan and without xylitol. Whole saliva and pooled plaque samples were
      obtained after 2, 4 and 6 months. When comparing the MS counts within the groups
      for saliva and plaque samples, Total-Xylitol showed significant reduction at all
      three sampling occasions (p < 0.001). Mean reduction at the 6-month sample for
      saliva was 0.81/ml and for plaque 0.89 per sample (log values). ANOVA revealed
      significant differences between Total-Xylitol and the two other products at 6
      months for MS in saliva and dental plaque. The conclusion from this 6- month
      study is that the addition of 10% xylitol to a triclosan-containing dentifrice
      reduces the number of MS in saliva and dental plaque.

PMID- 11961329
TI  - Fluoride concentrations in saliva and dental plaque in young children after
      intake of fluoridated milk.
AB  - This study determined fluoride (F) concentrations in whole saliva and dental
      plaque after intake of fluoridated milk using a randomised crossover experimental
      design. Eighteen healthy children (6-8 years) were subjected to each of four
      different 3-day drinking regimens: (a) 200 ml F-free tap water; (b) 200 ml tap
      water with 1.0 mg F; (c) 200 ml standard milk, and (d) 200 ml standard milk with
      1.0 mg F. A washout period of 7 days was organised between the different drinking
      regimens. All children used F-free toothpaste prior to and during the trial and
      were instructed to avoid F-rich food and drinks. F concentration in unstimulated
      whole saliva was determined at baseline and after 15 and 120 min and in plaque
      samples at baseline and after 2 h. The mean baseline values ranged from 0.01 to
      0.02 mg F/l in saliva and between 10.4 and 14.2 mg F/l in dental plaque. A
      statistically significant (p < 0.05) increase of F was disclosed in saliva 15 min
      after drinking F-containing milk and water (0.052 and 0.058 mg F/l,
      respectively). After 2 h, the salivary F(-) concentrations were back to baseline
      values. In the plaque, however, a statistically significant (p < 0.01) twofold
      increase was found at 2 h after the intake of fluoridated milk and water,
      respectively. The results indicate that consumption of fluoridated milk
      contributes to a F storing process with significantly elevated F concentrations
      in dental plaque up to 2 h after intake. Further studies are required to
      determine the 'therapeutic concentration' of F in dental plaque after intake of
      fluoridated milk.

PMID- 11961330
TI  - Changes in lactate and other ions in plaque and saliva after a fluoride rinse and
      subsequent sucrose administration.
AB  - The purpose of this study was to examine plaque and saliva composition after a
      fluoride rinse and subsequent sucrose application. Fifteen subjects accumulated
      plaque for 48 h, and then rinsed with a fluoride rinse based on 228 microg/g
      (ppm) Na2SiF6 and some received no rinse. After 60 min, upper and lower buccal
      molar plaque samples and 1-min saliva samples were collected. The subjects then
      rinsed with 10% g/g sucrose solution, and 7 and 15 min later, a second and a
      third set of samples were collected. Plaque fluid and clarified saliva were then
      recovered from these samples by centrifugation, and the remaining plaque acid
      extracted. The plaque fluid, centrifuged saliva, and plaque extract samples were
      then analyzed using micro techniques for pH, free calcium, phosphate, organic
      acids (plaque fluid and saliva only) and fluoride. Considering both the fluoride
      rinse and no-rinse groups, the most notable compositional changes in saliva 7 min
      after the sucrose rinse were pH -0.40 unit, free calcium 0.42 mM, lactate 5.2 mM,
      phosphate -1.3 mM, and fluoride 2.8 microM; while in plaque fluid, the
      corresponding changes were pH -1.59 unit, free calcium 1.5 mM, lactate 35 mM,
      phosphate -1.6 mM and fluoride -26 microM. After sucrose rinsing, undersaturation
      was found with respect to dicalcium phosphate dihydrate in saliva and plaque
      fluid and with respect to tooth enamel in some plaque fluid samples. Plaque fluid
      composition appeared to be strongly influenced by salivary clearance, diffusive
      loss of ions into the water phase of the rinse, and lower jaw pooling of the
      sucrose and fluoride components of the rinses. After the experimental rinse, the
      fluoride concentration in plaque fluid [86 +/- 22 mM (upper molar site), 162 +/-
      150 mM (lower molar site)], saliva (26 +/- 18 mM), and whole plaque [99 +/- 97
      microg/g (upper molar site), 197 +/- 412 microg/g (lower molar site)] was
      comparable to the values in previous studies using this rinse. These very high
      plaque fluid fluoride concentrations, compared with the 'no-rinse' samples,
      induced an approximately 0.3-unit increase in the plaque fluid pH 7 min after the
      sucrose rinse, a small decrease (approximately 20%) in lactate production and a
      modest increase in enamel saturation. Although these changes were all
      statistically significant, no correlation was found between the decrease in
      lactate concentration and plaque fluid fluoride, pH or whole plaque fluoride.

PMID- 11961331
TI  - Acidogenicity of buccal plaque after a single rinse with amine fluoride -
      stannous fluoride mouthrinse solution.
AB  - Caries and gingivitis prevention may benefit from chemotherapeutic plaque
      control, therefore we compared in a cross-over study with 5 subjects the anti
      acidogenic effects of a single use of AmF-SnF2 mouthrinse solutions (Meridol with
      and without 5% alcohol) with baseline and with the effects of a placebo and a
      chlorhexidine mouthrinse (CHX). Buccal plaque was collected 0.5, 3 and 8 h after
      the subjects used one of the mouthrinses, each time before and after a rinse with
      10% sucrose to induce lactic acid production. Samples were analysed for acid
      anions by capillary electrophoresis and for protein. At 0.5 h after the use of
      AmF-SnF2 or CHX, the concentration of acetate in resting plaque was 70% lower
      than at baseline or after using the placebo. Average post-sucrose acetate and
      lactate concentrations in the placebo group were 30-80% higher than at baseline;
      up to 3 h this difference was significant. 8 h after using AmF-SnF2 or CHX, the
      post-sucrose acetate and lactate concentrations were still 30-50% lower than
      after the placebo, and up to 40% lower than at baseline. To conclude, AmF-SnF2 in
      both Meridol formulations and CHX were shown to have a similar potency to inhibit
      acid production after a single rinse.

PMID- 11961332
TI  - The influence of salivary variables on fluoride retention in dental plaque
      exposed to a mineral-enriching solution.
AB  - This study was carried out to examine interindividual differences in salivary
      variables related to plaque accumulation and to estimate their influence on the
      fluoride retention in plaque in vivo by a mineral-enriching solution. Two saliva
      samples were taken from 10 subjects, once after brushing and once after 24 h
      without brushing. Calcium, phosphate and monofluorophosphatase (MFPase) activity
      in the saliva samples were determined. The salivary flow rate and the debris
      index were also recorded. After plaque had formed over 3 days within in situ
      plaque-generating devices, subjects were instructed to rinse with a mineral
      enriching mouthrinse three times a day on 4 consecutive days. Plaque exposed to
      distilled water plus flavoring agents served as a control. Fluoride-free
      dentifrice was used during the experimental period. Twenty-four hours after the
      last rinsing, the samples were removed from the mouth, and fluoride and mineral
      distributions in plaque analyzed using a method previously reported by the
      authors. Salivary flow, MFPase activity and calcium concentration in saliva were
      significantly higher after 24 h of plaque accumulation. Rinsing with the mineral
      enriching solution produced retention of fluoride and phosphate in the outer and
      middle layers of plaque. Salivary calcium concentration had a direct effect on
      fluoride uptake in plaque, but no obvious relationship was found between other
      salivary variables and the plaque fluoride retention. The salivary calcium effect
      may be due to enhanced bacterial cell wall binding of fluoride via calcium
      bridging.

PMID- 11961333
TI  - Fluoride and urea chewing gums in an intra-oral experimental caries model.
AB  - The aim of the present investigation was to evaluate the effect of sugar-free
      chewing gums containing fluoride (F) and urea in an intra-oral experimental
      caries model. Placebo chewing gums (without any active ingredient) and no gum
      served as controls. Fifteen subjects participated in a cross-over, single-blind
      study. Demineralised enamel and dentine blocks were embedded in circular plastic
      discs and bonded to the buccal surfaces of the lower canines and first premolars.
      The discs were removed and analysed using transversal microradiography after each
      of the six 4-week periods during which the subjects used either test or placebo
      products or no product. The results revealed that frequent use of sugar-free
      chewing gum is sufficient to inhibit further demineralisation of previously
      demineralised enamel and dentine specimens in the oral cavity. Comparing F, urea
      and placebo gums, the data showed that there was little or no difference between
      the products, except for an inhibitory effect on the chewing side of the
      dentition after using F chewing gums.

PMID- 11961334
TI  - Further modification to soft drinks to minimise erosion. A study in situ.
AB  - Soft drinks have been successfully modified to reduce enamel erosion. The aim of
      this study was to further modify an original low erosive blackcurrant drink
      product by the addition of a gum, to manipulate more favourably other drink
      parameters. The study was a single-blind, randomised four treatment crossover
      design involving 12 healthy volunteers. During 10 working-day study periods,
      subjects wore enamel samples in the mid palatal region of a removable appliance.
      Specimens were taped to expose a 2-mm enamel window. The drinks under test were:
      (1) Orange juice, (2) Original blackcurrant drink, (3) Water, and (4)
      Experimental blackcurrant drink. Drinks were imbibed at 250-ml volumes 4 times a
      day during appliance wearing from 09.00 to 17.00. Appliances were removed at
      lunchtime. Measurements of specimens were made at baseline, 2, 5 and 10 days
      using a profilometer. One 5-day and one 10-day specimen from each subject during
      each treatment were ultrasonicated. Significant differences, in erosion between
      drinks, were seen at days 5 and 10. Comparisons of preselected pairs of drinks of
      interest showed significantly reduced erosion by the two blackcurrant drinks
      compared to orange juice with no significant differences from water. The original
      blackcurrant drink produced significantly less erosion than the experimental
      drink. Ultrasonication removed enamel from the Orange juice specimens but very
      little from those exposed to water and the two blackcurrant drinks. Extrapolating
      the effects of both blackcurrant drinks suggested that alone they should not
      cause significant clinical erosion in a lifetime's intake of 1 litre per day.

PMID- 11961335
TI  - Fluoride is unable to reduce dental erosion from soft drinks.
AB  - The main aim of the present study was to compare the erosive capabilities of some
      fruit-flavoured drinks, fresh or saturated with CaF2, with their content of acids
      and with previous results from some carbonated soft drinks. The other aim was to
      measure and compare the rates of dissolution of CaF2 in some carbonated and non
      carbonated drinks and water. Seven commercially available fruit-flavoured drinks
      were diluted for drinking. Two human molars, each with two approximately 4 x 4 mm
      windows, were exposed continuously to 500 ml of each drink with or without prior
      equilibration with CaF2 under gentle agitation for 48 h. The depths of the
      erosions were then measured on microradiographs made from sections. Dissolution
      rate of CaF2 was measured by suspending 0.5 g of the salt in 0.5 litre of the
      drinks for 2, 10 and 60 min followed by solution analysis. The pH of the drinks
      was 2.83-3.51. The amount of NaOH required to bring pH to 5.5 ranged from 12-42
      mmol/l, which is more than the amount necessary for most carbonated soft drinks.
      Equilibration with CaF2 gave total fluoride concentrations of 3-8 ppm. The depths
      of the lesions induced by the drinks without added fluoride were 450-625 microm
      whilst those developed by the drinks equilibrated with CaF2 were 350-625 microm.
      The dissolution of CaF2 was faster in the carbonated drinks and in distilled
      water than in the non-carbonated drinks. In conclusion, non-carbonated fruit
      flavoured drinks contain considerable amounts of acids which, in vitro, induce
      erosions in teeth similar to those induced by carbonated soft drinks. Saturation
      with CaF2 reduced the in vitro development of erosions by 28% induced by drinks
      with pH above 3; in drinks with pH below 3, erosions were not affected by pH,
      despite total fluoride concentrations of up to 20 ppm.

PMID- 11961336
TI  - Effect of omeprazole on regional and temporal variations in intragastric acidity.
AB  - BACKGROUND: Conventional techniques for measuring gastric acidity have
      demonstrated the decrease in gastric acidity produced by proton pump inhibitors
      (PPI); however, such techniques do not detect transient or localized pH changes
      which may modify the intragastric environment without affecting the therapeutic
      efficacy of PPIs. AIM: To investigate local and temporal variations in
      intragastric pH and to test the hypothesis that omeprazole produces prolonged,
      generalized gastric anacidity (pH >6). METHODS: A single-blind study was
      conducted with triple-point 24-hour gastric pH-metry on days 7, 14 and 21 in 14
      healthy, Helicobacter pylori-negative volunteers (7 M; 20-46 years) who received
      placebo for 7 days, followed by omeprazole 20 mg daily for 14 days. RESULTS:
      Omeprazole increased the median 24-hour pH significantly in the distal corpus
      (placebo: 1.3 (95% CI 1.1 to 1.6); omeprazole week 1: 4.0 (2.6-5.0); omeprazole
      week 2: 4.0 (2.8-4.6)) and at all other gastric recording sites (p < 0.01). At
      both corpus sites, nocturnal pH was lower and mealtime pH was higher than the non
      meal daytime pH during placebo and both omeprazole administration periods; in the
      antrum, however, the major difference noted was that meal-time pH was higher than
      non-meal daytime pH. Antral pH was lower during meals and higher at night than
      proximal corpus pH. During placebo, gastric pH >6.0 was observed at 1 site only
      for 1.7% (median; 95% CI 0.4-3.3%), at 2 sites simultaneously for 0.24% (0.0
      1.0%) and at 3 sites for 0.0% (0.0-0.28%), respectively, of the recording
      periods; during the second week of omeprazole, the equivalent results were 7.7%
      (1.4-14.0%), 4.9% (0.21-15.7%) and 4.7% (0.0-9.9%), respectively. CONCLUSIONS:
      Omeprazole, 20 mg daily, does not produce gastric anacidity despite significant
      increases in median 24-hour pH values. The time-, meal- and site-related
      variations in gastric pH observed under normal physiological conditions are seen
      to persist, with prolonged periods of low pH throughout the stomach and
      preservation of the normal, meal-related rise and nocturnal fall in gastric pH
      during omeprazole administration.

PMID- 11961337
TI  - Relevance of underlying disease and bacterial vacA and cagA status on the
      efficacy of Helicobacter pylori eradication.
AB  - AIM: To study the effects of Helicobacter pylori associated diseases and the
      bacterial vacA and cagA statuses on the efficacy of H. pylori eradication.
      METHODS: A prospective study in a consecutive series of outpatients of a
      gastroenterological institution and of a primary practice. A series of 146 H.
      pylori positive patients with peptic ulcer disease (PUD; n = 40) or nonulcer
      dyspepsia (NUD; n = 106) were evaluated. H. pylori vacA genotpyes and cagA status
      were determined directly in gastric biopsy specimens by polymerase chain
      reaction. The patients were treated with triple-therapy regimens consisting of a
      proton pump inhibitor and two antibiotics twice daily for 7 days. Reevaluation of
      H. pylori was determined 4-5 weeks later by endoscopy or 13C urea breath test.
      RESULTS: 123 patients completed the study. In 8 patients, colonization with two
      or more H. pylori strains was found. The overall cure rate was 84.6% (104/123).
      The eradication rates were significantly higher in patients with PUD (94.4%,
      34/36) than in those with NUD (81.6%, 71/87; p < 0.05). In patients with cagA
      positive H. pylori strains, the eradication rate was 89.0% (73/82) as compared
      with 78.8% (26/33) in those with cagA-negative strains (p = 0.15). The vacA
      genotype had no effect on the efficacy of H. pylori eradication. CONCLUSION:
      Using 1-week triple-therapy regimens, treatment of H. pylori infection is more
      effective in patients with PUD than in those with NUD.

PMID- 11961338
TI  - Lack of therapeutic effect of a specially designed yogurt for the eradication of
      Helicobacter pylori infection.
AB  - BACKGROUND: Current antibiotic treatment for Helicobacter pylori infection is
      often associated with frequent adverse effects and resistance to antibiotics.
      Alternative treatment methods to control H. pylori infection are needed. Some
      specific strains of lactic acid bacteria (probiotics) in dairy products are known
      to inhibit the growth of H. pylori in vitro. A clinical trial was conducted to
      see the efficacy of a specially designed yogurt product containing specific
      probiotics on the eradication of H. pylori. METHOD: The yogurt was prepared using
      three Lactobacillus spp. (L. acidophilus and L. casei) and one commercial starter
      culture (L. acidophilus, L. bulgaricus and Streptococcus thermophilus). All these
      cultures were previously evaluated, and found to have strong in vitro inhibitory
      effects on the growth of H. pylori. Twenty-seven asymptomatic women positive for
      H. pylori on gastric biopsy and 13C urea breath test were recruited, and
      administered 175 ml of the yogurt three times a day for 30 days. The 13C urea
      breath test was administered again, one month after stopping the yogurt treatment
      to detect the presence of H. pylori. RESULTS: In 26 of 27 subjects, the urea
      breath test values remained positive, indicating that the consumption of the
      yogurt had no effect on the eradication of H. pylori. CONCLUSION: Although the
      designed fermented milk containing lactobacilli is very effective in the
      inhibition of H. pylori growth in vitro, eradication of this infection in humans
      is difficult to achieve by consuming this product.

PMID- 11961339
TI  - Effect of lipopolysaccharide on peptide transporter 1 expression in rat small
      intestine and its attenuation by dexamethasone.
AB  - BACKGROUND/AIM: The peptide transporter (PepT1) activity is upregulated or
      preserved under certain pathological conditions. The aim of this study was to
      investigate the PepT1 expression during lipopolysaccharide (LPS) treatment and
      the effect of dexamethasone on PepT1 expression. METHODS: Rats were injected
      daily for 3 days with (1) LPS; (2) LPS plus dexamethasone; (3) dexamethasone, and
      (4) saline only. Mucosal specimens were used for Northern blot and Western blot
      analyses. Tissues of small intestine were taken for histological studies. In
      addition, tumor necrosis factor alpha and interleukin 1 beta levels were
      determined 3 h after single injections of the above mediators. RESULTS: Northern
      blot analysis revealed that LPS treatment significantly decreased the expression
      of mRNA for PepT1 (32-62% of controls) at different time points. In the LPS +
      dexamethasone group, it was 66-95% of controls. The protein level of PepT1 in the
      jejunum was consistent with the mRNA expression level. Immunohistochemistry also
      showed a reduction of PepT1 immunoreactivity in the LPS group. LPS treatment
      resulted in increased tumor necrosis factor alpha and interleukin 1 beta levels,
      but dexamethasone treatment profoundly counteracted the cytokine production.
      CONCLUSIONS: This is the first report that LPS treatment reduces PepT1 expression
      in the rat small intestine. Short-term treatment with dexamethasone attenuated
      the effects of LPS by decreasing the cytokine levels.

PMID- 11961340
TI  - Effect of fasting on diarrhoea in collagenous colitis.
AB  - BACKGROUND/AIM: Diarrhoea in collagenous colitis has been considered as secretory
      though the pathophysiology has been studied thoroughly in only a few patients.
      The result of fasting is one way to distinguish between secretory and osmotic
      diarrhoea. Our aim was to investigate the effect of fasting on diarrhoea in
      collagenous colitis. METHODS: Fourteen patients with collagenous colitis were
      admitted to the hospital for investigation. All were female. Five of these did
      not have diarrhoea during admission and were excluded. Stools were examined for
      weight, electrolytes, pH, fat and osmolality during a period on a normal diet and
      during fasting. RESULTS: During the fasting period the faecal weight was
      significantly reduced from median 757 (440-3,198) to 191 (22- 2,197) g. The
      faecal sodium concentration was also reduced, though not significantly, during
      fasting from median 65 (29-85) to 45 (19-88) mmol/l. The osmotic gaps varied
      according to the method of calculation applied. CONCLUSIONS: The data indicate
      that the cause of the diarrhoea in collagenous colitis could be multifactorial.
      In some patients an osmotic factor dominates and in others a secretory factor,
      while in some patients a combination of both seems to exist.

PMID- 11961341
TI  - Effect of cholecystokinin-B gastrin receptor blockade on chemically induced colon
      carcinogenesis in mice: follow-up at 52 weeks.
AB  - BACKGROUND/AIMS: The potential role of gastrin and the cholecystokinin-B (CCK
      B)/gastrin receptor in the genesis of colon cancer is debated. Aberrant crypt
      foci (ACF) are considered to be preneoplastic lesions of colon cancer. We aimed
      to assess whether the CCK-B/gastrin receptor antagonist, CR2945, may prevent the
      development of ACF and adenocarcinoma in the experimental model of
      dimethylhydrazine (DMH)-induced colorectal cancer. MATERIALS AND METHODS: 226 CD1
      mice were randomized into 3 groups (sham, control and treated) and received
      intraperitoneal injections of NaCl 0.9%, DMH, and DMH + CR2945, respectively, for
      5 weeks. 168 mice were sacrificed at 15, 38, 45 and 52 weeks after the first
      injection day. The colon and rectum were investigated for frequency, multiplicity
      and distribution of ACF as well as for adenocarcinoma at histology. The
      expression of gastrin was assessed in tumor samples at histology by
      immunohistochemistry. RESULTS: ACF frequency and multiplicity significantly
      increased with time in both controls and treated mice with no difference between
      groups except that at week 45. 38.8% of controls and 14.3% of treated mice
      developed cancer (p = 0.004). No cancer was positive for gastrin at
      immunohistochemistry. The mean number of cancers per mouse and the proportion of
      mice with cancer increased with time with statistically significant difference
      between controls and treated mice at week 38 only but not afterwards. A
      significant correlation between cancer and ACF frequency (r = 0.35) and
      multiplicity (r = 0.25) was observed. CONCLUSIONS: Our findings support the
      preneoplastic significance of ACF and indicate that CR2945 treatment does not
      interfere with the DMH-induced carcinogenic process.

PMID- 11961342
TI  - Relationship between the effects of cisapride on gastric emptying and plasma
      glucose concentrations in diabetic gastroparesis.
AB  - BACKGROUND/AIMS: The effect of erythromycin on gastric emptying is attenuated
      during hyperglycaemia. The aim of this study was to determine in patients with
      diabetic gastroparesis whether the effect of cisapride on gastric emptying of
      solids and liquids is influenced by the plasma glucose concentration. METHODS:
      Nineteen patients with type 1 diabetes mellitus, who had delayed gastric emptying
      of solids and/or liquids, were studied. On 2 separate days, each patient received
      cisapride (20 mg) or placebo orally 60 min before scintigraphic measurement of
      gastric emptying of a mixed solid (ground beef) and liquid (dextrose) meal. The
      plasma glucose concentrations were measured at -5, 30, 60, 90, and 120 min during
      each gastric emptying measurement. RESULTS: Cisapride accelerated both solid
      (retention at 100 min 43 +/- 4 vs. 69 +/- 4%, p < 0.001) and liquid (T50 27 +/- 2
      vs. 39 +/- 2 min, p < 0.001) gastric emptying. The mean plasma glucose level was
      not significantly different after placebo when compared with cisapride (19.5 +/-
      1.1 vs. 18.2 +/- 1.0 mmol/l). The change in the 50% emptying time (T50) for
      liquid, but not solid, emptying was related (r = 0.55, p = 0.01) to the change in
      the plasma glucose AUC from 0 to 30 min between the placebo and cisapride tests,
      i.e., the acceleration was greater if the plasma glucose concentration was
      relatively less during the gastric emptying test performed on cisapride.
      CONCLUSION: The effect of cisapride on gastric emptying, at least that of
      liquids, in patients with diabetic gastroparesis appears to be dependent on the
      plasma glucose concentration.

PMID- 11961343
TI  - CCK-stimulated changes in pancreatic acinar morphology are mediated by rho.
AB  - BACKGROUND/AIMS: Treatment of isolated pancreatic acini with high concentrations
      of cholecystokinin (CCK) is known to induce rapid changes in the cellular
      morphology. The signalling pathways remain to be characterized. METHODS:
      Pancreatic acini were permeabilized by digitonin and incubated with various
      agents. The acinar morphology was investigated by microscopy. The activation of
      p125 focal adhesion kinase was determined by Western blot analysis. Amylase was
      measured photometrically. RESULTS: The functionality of the permeabilized acini
      was tested by measuring stimulated amylase release. 300 microM GTP gamma S was
      almost as efficient as CCK to stimulate amylase release, while 300 microM GDP
      beta S inhibited the CCK-stimulated amylase release. Stimulation of permeabilized
      acini with 0.1 microM CCK induced similar morphological changes as in
      unpermeabilized acini. Incubation of permeabilized acini with GTP gamma S
      mimicked the CCK-induced changes, whereas a preincubation with GDP beta S
      prevented the CCK effects on the acinar morphology. Inhibition of the small G
      protein rho, which activates p125 focal adhesion kinase, by Clostridium botulinum
      C3 transferase also prevented the CCK-stimulated morphological changes.
      Preincubation of intact acini with cell-permeable inhibitors of protein kinase C,
      MEK or p38MAPK, or with the intracellular calcium chelator BAPTA/AM was without
      significant effect on the CCK-stimulated changes. CONCLUSION: The CCK-induced
      morphological changes seem to be mediated by G protein signalling via the small G
      protein rho and the associated activation of p125 focal adhesion kinase.

PMID- 11961345
TI  - Pheochromocytoma presenting as an abdominal emergency: association with
      perforation of the colon.
AB  - A pheochromocytoma is a rare tumor derived from the adrenal medulla (or from
      chromaffin cells of sympathetic ganglia). Its symptoms derive mostly from the
      excessive release of catecholamines (adrenaline and noradrenaline). Hypertension
      is the most recognized feature of this disease, but gastrointestinal
      manifestations can on rare occasions be just as serious and life threatening.
      This report describes a rare case of a 70-year-old woman with pheochromocytoma
      who developed an acute abdominal emergency with shock and panperitonitis as a
      result of perforation of the descending colon which was effectively treated by
      surgical removal of the tumor and the perforated colon. There have been 2 such
      cases in the English literature in whom a pheochromocytoma was associated with
      perforation of the colon. Successful surgical removal of such a pheochromocytoma
      has been not reported previously. Our case demonstrates the importance of
      recognizing that a pheochromocytoma presents with a wide spectrum of
      manifestations, and rapid treatment brings improvement to the patient.

PMID- 11961344
TI  - Effect of the somatostatin analogue lanreotide on meal-stimulated portal blood
      flow in patients with liver cirrhosis.
AB  - BACKGROUND: Lanreotide, a new long-acting somatostatin analogue, has been shown
      to inhibit the meal-stimulated increase of splanchnic blood flow in healthy
      volunteers. To date, similar data in patients with liver cirrhosis have not been
      available. We have examined the effect of lanreotide compared with placebo on
      meal-stimulated portal blood flow in patients with liver cirrhosis using Doppler
      ultrasound. METHODS: 20 cirrhotic patients (placebo n = 12, lanreotide n = 8)
      with proven portal hypertension were studied after an overnight fast. Lanreotide,
      at a dose of 100 microg/h, was infused intravenously over 7 h after a 1-hour
      basal period. In parallel to the intravenous infusion, a liquid test meal (Ensure
      plus, 1.5 kcal/min) was perfused for 7 h through an intraduodenal tube at a rate
      of 3 ml/min. Blood pressure, heart rate and portal vein blood flow (PVF, ml/min,
      Doppler technique) were determined at regular intervals. RESULTS: Baseline PVF
      amounted to 725 +/- 182 ml/min in the placebo and to 917 +/- 252 ml/min in the
      lanreotide group (n.s.). The meal-stimulated increase in PVF was blunted by
      lanreotide (AUC, % x min): 62,709.6 +/- 6,817 (placebo) vs. 45,237 +/- 2,507
      (lanreotide), p < 0.05. Lanreotide also blunted the postprandial increase in
      heart rate for the first 2 h of meal perfusion. CONCLUSIONS: Because of potent
      inhibition of postprandial splanchnic hyperemia in patients with liver cirrhosis,
      lanreotide may be useful in the treatment of complications of portal
      hypertension.

PMID- 11961347
TI  - MRCP in situs inversus.

PMID- 11961348
TI  - Use of laser in the relief of malignant dysphagia: a district hospital
      experience.
AB  - BACKGROUND: Endoscopic laser treatment offers rapid relief from dysphagia. The
      major drawback of laser therapy is the need for repeated treatment at 4- to 6
      week intervals. Laser therapy is often done in tertiary referral centres and is
      said to require special expertise that is not available in many peripheral
      hospitals. For smaller centres, intubation is likely to be the only treatment
      option even though it gives less quality of palliation. AIM: To report the
      experience of a district general hospital in laser treatment of malignant
      dysphagia. METHODS: A retrospective study on patients who had laser therapy for
      relief from malignant dysphagia from march 1995 to January 2000 was performed in
      a district general hospital in the UK. RESULTS: Forty patients (25 males and 15
      females) with histologically proven oesophageal carcinoma were unsuitable for
      surgical resection. Trainees, under supervision, did 20% of the sessions.
      Treatment was done on a day case basis with no outpatient follow-up. The patients
      had direct access to the service whenever dysphagia got worse. The median number
      of sessions per patient was 4 (range 1-13). The median palliation period per
      session was 7 (range 1-32) weeks. The median total palliation period was 7
      months. There was no procedure-related mortality. CONCLUSION: Laser therapy is a
      safe, easy to teach and learn technique for relief from malignant dysphagia. It
      can be done on a day case basis with minimum need for follow-up and hospital
      visits. Such a service could be provided in a district general hospital set-up
      once equipment and experience are available, thus saving patients from having to
      travel to specialist units.

PMID- 11961349
TI  - Serum soluble interleukin-2 receptor as a predictor of lymph node metastasis in
      early gastric cancer.
AB  - BACKGROUND: In the present study, we investigated the clinical significance of
      serum soluble IL-2R as a predictor of lymph node metastasis in patients with
      early gastric cancer. PATIENTS AND METHODS: Seventy-four patients with early
      gastric cancer were enrolled in this study. Levels of serum soluble IL-2R were
      measured by an enzyme-linked immunosorbent assay. RESULT: Significant differences
      in serum soluble IL-2R between the control group and cases of T1 were not
      recognized. On the other hand, levels of serum soluble IL-2R in 74 patients with
      early gastric cancer (T1) were significantly lower than those of T2, T3, and T4
      (p < 0.05). There were no significant differences in serum soluble IL-2R between
      cases of mucosal and submucosal invasion (379 +/- 42 vs. 382 +/- 35 U/ml). Six of
      35 patients with submucosal invasion (17.1%) had lymph node metastasis, but none
      of the 39 patients with mucosal invasion. In the 6 cases showing lymph node
      metastasis, the macroscopic types were IIc + Ul(+) in 4, and IIc + IIa and IIc +
      IIb in 1, respectively. Histopathologically, there were 5 poorly and 1 moderately
      differentiated adenocarcinomas. In 6 cases with lymph node metastasis, serum
      soluble IL-2R levels were significantly higher than in those without lymph node
      metastasis (556.8 +/- 73 vs. 329 +/- 22 U/ml, respectively, mean +/- SEM, p <
      0.05). Five of these 6 cases demonstrated statistically significantly increased
      levels of serum soluble IL-2R (sensitivity 83%, specificity 63%), suggesting
      serum soluble IL-2R as a predictor of lymph node metastasis in early gastric
      cancer (p < 0.05). CONCLUSION: According to these data, in patients of early
      gastric cancer with increased levels of serum soluble IL-2R, endoscopic mucosal
      resection or minimal invasive gastrectomy without dissection of regional lymph
      nodes should be avoided, since there is a high risk of lymph node metastasis.

PMID- 11961350
TI  - Total gastrectomy is not always necessary for advanced gastric cancer of the
      cardia.
AB  - BACKGROUND: It is unclear whether total gastrectomy (TG) is always necessary for
      gastric cancer of the cardia. We therefore investigated whether cardiac cancers
      treated by TG would have been cured by proximal gastrectomy (PG). METHODS:
      Photocopies of the resected stomachs of 55 patients who had received TG for
      cardiac cancer were reviewed. A simulated resection line for PG was drawn
      connecting a point 5 cm from the pyloric ring on the lesser curvature with a
      point 15 cm from the pyloric ring on the greater curvature. The distal surgical
      margin between the tumor edge and the simulated resection line was measured, and
      lymph nodes (LN) dissected surgically were examined for tumor involvement.
      RESULTS: Tumor location fell into three categories, upper-middle (UM, n = 28),
      upper (U, n = 18), and upper-esophagus (UE, n = 9). The means of the simulated
      surgical margins were 1.0 cm for UM, 4.7 cm for U, and 5.7 cm for UE tumors. UE
      tumors had no metastasis to No. 4d, 5, or 6 LN, and only one U tumor showed
      metastasis to No. 4d and 5 LN. In contrast, UM tumors had a higher incidence of
      these nodes involved. CONCLUSION: Advanced gastric cancer located in the U or UE
      regions is mostly curable by PG.

PMID- 11961351
TI  - Reoperative surgery for postcholecystectomy bile duct injuries.
AB  - BACKGROUND: Surgical repair for a postcholecystectomy bile duct injury can be
      complicated by the development of an anastomotic stricture which necessitates re
      intervention. The authors reviewed their experience with patients requiring re
      operation after unsuccessful surgical repair of the bile duct injury, to analyze
      the possible causes of the failure of the operative procedure and the long-term
      outcome following revisional surgery. METHODS: Retrospective analysis of the
      records of 41 patients referred to a tertiary care center for the management of
      recurrent stricture following surgical repair performed for a postcholecystectomy
      bile duct injury. RESULTS: Before referral, 69 operative procedures had been
      performed on these 41 patients. Factors likely to be associated with increased
      chances of failure of the biliary reconstructive procedures included presentation
      with cholangitis after the biliary injury, no cholangiographic study before the
      surgical repair and surgical intervention within 3 weeks of the injury. Thirty
      seven (90%) patients were found to have strictures at or above the level of
      confluence of right and left hepatic ducts, while at the time of the index repair
      only 12 (29%) patients had an injury at that level. Revisional surgery in all the
      patients was a Roux-en-Y hepaticojejunostomy. One patient died, 2 patients with
      multiple previous operations developed recurrence and needed intervention again.
      Over a mean follow-up period of 4.2 years, 90% patients had a satisfactory
      outcome. CONCLUSION: Development of recurrent stricture following surgical repair
      of a postcholecystectomy biliary injury can be related to the technique and
      timing of the surgical procedure, the complication may therefore be avoidable in
      some patients. In experienced hands the results of revisional surgery are good
      but are adversely affected as the number of previous repairs increases.

PMID- 11961352
TI  - Clinical experience with different techniques of pancreatic head resection for
      chronic pancreatitis.
AB  - BACKGROUND/AIMS: Recently organ-saving procedures have become popular in the
      treatment of chronic pancreatitis with head enlargement. The purpose of this
      study is to compare the results of three different procedures. METHODS: Between
      1991 and 1998, 32 Beger operations, 13 Frey procedures and 21 pylorus-preserving
      pancreatoduodenectomies (PPPDs) were performed. The pre-, intra- and
      postoperative data were detailed. During the follow-up examination the quality of
      life, body weight, consumption of alcohol and enzymes, as well as the
      carbohydrate metabolism were checked. RESULTS: Considering the operative and late
      mortality and reoperation rate, there was no difference between the procedures.
      The postoperative hospitalization time was the shortest after the duodenum
      preserving pancreatic head resections (Beger and Frey). While the rate of early
      morbidity was higher after PPPDs, there was no difference in late morbidity
      between the groups. The condition of the patients was better and the development
      rate of diabetes was lower after the Beger procedure than after PPPDs.
      CONCLUSION: Consequently duodenum-preserving pancreatic head resections seem to
      be more advantageous than PPPD. Nevertheless the latter operation is the only
      possibility in some situations.

PMID- 11961353
TI  - Management of fistulas in Crohn's disease.
AB  - AIM: This study was conducted to clarify operative indications, surgical
      treatment, and postoperative complications of intra-abdominal fistulas in Crohn's
      disease. METHODS: Of 213 patients undergoing surgical treatment for Crohn's
      disease in our institution between 1972 and 2000, 55 patients (25.8%) found to
      have 81 intra-abdominal fistulas were retrospectively reviewed. RESULTS: The most
      common indication for surgery was intestinal obstruction. A fistula represented a
      single indication for surgical treatment in 9 operations (15.5%). All patients
      with intra-abdominal fistulas underwent resection of the diseased intestinal
      segment. Closure of the fistulous defect of the affected lesion was achieved by
      suture (n = 27), stapled fistulectomy (n = 12), or resection (n = 11). Resection
      of the diseased bowel was achieved by en bloc removal of the fistula in 15 cases.
      When the fistula opened through the abdominal wall (n = 12), the diseased portion
      of the intestine was resected, and the fistulous tract was debrided. Only 1
      patient died postoperatively from multiple organ failure because of anastomotic
      breakdown. CONCLUSIONS: The surgical treatment of an intra-abdominal fistula in
      Crohn's disease is based on resection of the diseased intestinal segments, and
      the affected lesion can be sutured. This procedure can be achieved safely, and
      the incidence of postoperative complications is low.

PMID- 11961354
TI  - Acute appendicitis during pregnancy.
AB  - BACKGROUND: To analyze the diagnosis and surgical treatment of acute appendicitis
      during pregnancy. METHODS: The records of 24 pregnant patients who underwent
      surgery with preliminary diagnosis of acute appendicitis between January 1990 and
      July 2000 were reviewed retrospectively. RESULTS: Between January 1990 and July
      2000, there were 31,480 deliveries and the incidence of acute appendicitis was
      1/1,312. Twenty patients had pathologically proven acute appendicitis (83.3%). Of
      the remaining 4 patients, one had hemorrhagic ovarian cyst, one had ovarian cyst
      rupture and in two cases no surgical pathology was diagnosed. Gestational stage
      at the diagnosis was first trimester in 7 patients, second trimester in 12
      patients and third trimester in 5 patients. Five patients had abortions and
      premature delivery occurred in 2 patients. CONCLUSION: Diagnosis of acute
      appendicitis is difficult in pregnancy. Delay in diagnosis and surgery results in
      increase in complications. Emergency surgical intervention should be performed
      when acute appendicitis is suspected during pregnancy.

PMID- 11961355
TI  - Outcome of temporary stomas. A prospective study of temporary intestinal stomas
      constructed between 1989 and 1996.
AB  - PURPOSE: The purpose of this study was to examine the outcome of patients to whom
      a temporary stoma was constructed in our institution. METHOD: The outcome of
      patients operated on over an 8-year period was prospectively examined. Special
      attention was given to the influence of age on complications and closure of
      stomas. RESULTS: Between 1989 and 1996, a total of 349 intestinal stomas were
      constructed in 342 patients. In 141 of these patients, the stoma could be
      considered as temporary. The 30-day mortality rate was 7%. The overall
      complication rate was 50%. Pure stoma-related complications were observed in 12%
      of the patients. The final closure rate of temporary stomas was 67%. The closure
      rate was significantly higher if the temporary stomas were of the double-barrel
      type. There was no significant difference in the closure rate between patients
      with benign and malignant diseases, but the rate decreased significantly in age
      groups over 70 years. CONCLUSIONS: Forty percent of stomas constructed are
      considered as temporary, but only two-thirds of temporary stomas are closed
      subsequently. Especially end stomas tend to become permanent in patients over 70
      years of age, although the morbidity rates of stoma closure do not differ from
      those of younger patients.

PMID- 11961357
TI  - Partial fistulotomy and modified cutting seton procedure in the treatment of high
      extrasphincteric perianal fistulae.
AB  - AIM: In our prospective study the method of partial distal fistulotomy and
      modified cutting seton for high extrasphincteric perianal fistulae is discussed.
      METHODS: 10 patients (9 males and 1 female) with high extrasphincteric perianal
      fistulae were treated with partial distal fistulotomy and modified cutting seton.
      Four or five threads were introduced through the tract; one was tied tightly at
      the end of the operation, others were tightened every 10th day. While the tied
      thread cut the tissue, the others drained the tract. The follow-up period ranged
      from 3 months to 9 years. RESULTS: None of the patients developed major fecal
      incontinence. 2 of the 10 patients complained of incontinence due to flatus.
      CONCLUSION: Distal fistulotomy and modified cutting seton can be used in perianal
      fistulae with high anal or rectal opening, because it combines the effects of
      both cutting and loose setons and because the postoperative results regarding
      continence are satisfactory.

PMID- 11961356
TI  - Local formalin instillation: an effective treatment for uncontrolled radiation
      induced hemorrhagic proctitis.
AB  - AIM: The aim of this study was to evaluate the efficacy of local instillation of
      4% formalin in the management of uncontrolled radiation-induced and ischemic
      hemorrhagic proctitis. PATIENTS AND METHODS: Eight patients were reviewed.
      Operation characteristics, morbidity and long-term results were analyzed.
      RESULTS: All patients were followed for a median of 18 months. In 5 patients the
      bleeding stopped after a single treatment and in 3 after a second one. During
      follow-up no recurrent rectal bleeding occurred, no further medical treatment was
      needed and in all patients the complaints had disappeared. CONCLUSION: Local
      instillation of 4% formalin is an effective treatment for uncontrolled radiation
      induced and ischemic hemorrhagic proctitis.

PMID- 11961358
TI  - Paraesophageal bronchogenic cyst associated with multiple epithelial splenic
      cysts.
AB  - BACKGROUND: Bronchogenic cysts are rare congenital cystic lesions of foregut
      origin. They are the result of abnormal budding of the primitive tracheobronchial
      tube. Nonparasitic, true splenic cysts are another rare entity that might occur
      as incidental findings but may lead to deleterious courses in case of ruptures.
      CASE REPORT: We report here the first case of the uncommon association of a
      paraesophageal bronchogenic cyst and multiple primary splenic cysts in a 23-year
      old woman suffering from dysphagia and chest pain. Successful complete resection
      of the paraesophageal cyst was performed using an abdominal, transhiatal approach
      and splenic cysts were subjected to organ-preserving TA stapler resection.
      CONCLUSION: Thus far there is no proof or genetic indication for a direct
      association of bronchogenic cysts and multiple splenic cysts, however, the
      uncommon coincidence of both lesions in our patient might suggest a common
      origin. Difficulties in preoperative diagnosis, histopathological characteristics
      and surgical treatment modalities are presented.

PMID- 11961359
TI  - Cutaneous metastases from a gastrointestinal stromal tumor of the stomach: review
      of literature.
AB  - Gastrointestinal stromal tumors (GIST) are neoplasms of mesenchymal origin which
      may or may not be malignant. Malignant GIST rarely metastasize to distal organs.
      A case of cutaneous metastasis from GIST has been presented. This case is
      particularly interesting because not only did the patient have multiple
      metastases from GIST, but eventually developed cutaneous metastasis. This
      phenomenon has not been reported in the literature. The most current literature
      on gastrointestinal stromal tumors has been reviewed.

PMID- 11961360
TI  - Muir-Torre syndrome: a case for surveillance of the ampulla of Vater.
AB  - A 64-year-old man with Muir-Torre syndrome (MTS), a condition characterized by
      the association of multiple sebaceous tumours and kerato-acanthomas with internal
      malignancies, developed a carcinoma of the ampulla of Vater. This is the 2nd
      reported ampullary carcinoma in 205 reported cases of MTS, suggesting a higher
      prevalence in MTS patients than in the general population. As an ampullary
      carcinoma is potentially amenable to surgical resection, particularly when
      detected early, patients with MTS should undergo regular endoscopic surveillance
      of the ampulla of Vater.

PMID- 11961361
TI  - Diverticulitis presenting as a strangulated inguinal hernia.
AB  - BACKGROUND/AIM: Inguinal hernia is a common diagnosis for patients presenting
      with a painful groin mass; other potentially dangerous diagnoses may mimic a
      groin hernia. We present 3 unusual cases of diverticulitis with perforation. The
      resulting abscess presented clinically as an atypical strangulated inguinal
      hernia. METHODS/RESULTS: From July 1, 1999, to June 30, 2000, 344 patients were
      admitted to the Johns Hopkins Bayview Medical Center with the diagnosis of
      diverticulitis. Of these patients, 44 (12.8%) required surgical intervention. We
      report here 3 cases in that academic year of diverticulitis complicated by
      perforation and abscess formation that presented as atypical strangulated
      inguinal hernias. In addition to being rare and difficult to diagnose, such cases
      illustrate that a tender inguinal mass may not represent a hernia. CONCLUSIONS:
      The diagnosis of strangulated inguinal hernias remains primarily one of clinical
      suspicion. Radiologic and laboratory studies should augment, not replace, one's
      clinical diagnosis. In addition, the differential diagnosis of inguinal masses is
      discussed.

PMID- 11961362
TI  - Edward Delos Churchill (1897-1972). A giant in surgery and surgical education and
      leadership.

PMID- 11961363
TI  - The aging liver: structural and functional changes and their consequences for
      drug treatment in old age.
AB  - BACKGROUND/OBJECTIVE: Numerous age-related changes in hepatic structure and
      function have been described, although liver function seems to be quite well
      maintained in old age. Few consistent and reproducible observations and a lack of
      correlation between structural and functional data characterize the present state
      of our knowledge. In contrast to renal clearance, no equally reliable method
      exists to estimate hepatic drug clearance. The contribution of age to altered
      drug clearance in the elderly is difficult to assess as drug interactions,
      numbers and types of drugs taken at a time, underlying disease and increased
      interindividual variability are superimposed to the aging process. METHODS: A
      comprehensive computer-assisted search of the literature. RESULTS: A decline in
      liver volume and blood flow and a reduction in in vitro and in vivo metabolic
      capacity have been shown in older subjects, and the physiologic basis of reduced
      hepatic drug clearance in this age group. CONCLUSIONS: After decades of research
      into the matter, the old and well-known aphorism "start lower--go slower" is
      valid more than ever in the field of geriatric prescribing. Not only renally
      excreted drugs but also substances which are metabolized and excreted by the
      liver should be used at a starting dose which is 30-40% smaller than the average
      dose used in middle-aged adults.

PMID- 11961364
TI  - Cytokine levels and phagocytic activity in patients with Alzheimer's disease.
AB  - BACKGROUND: Clinical observations indicate that patients with Alzheimer's disease
      show a greater susceptibility to infections. One possible explanation is that
      this predisposition is due to alterations in their immune system. OBJECTIVE: To
      investigate this assumption, pro- and anti-inflammatory cytokines, as well as the
      phagocytic activity and superoxide anion generation was examined in aged
      individuals with and without Alzheimer's disease. METHODS: The production of IL
      1beta, IL-2, IL-6, TNFalpha and IL-10 by peripheral blood mononuclear cells from
      12 patients with Alzheimer's disease was compared with that of 12 age-matched
      individuals without any signs of dementia and 12 middle-aged healthy volunteers
      who served as an additional control. The engulfing capacity of the phagocytic
      cells was detected by counting cells containing latex beads and the number of
      particles internalized by each individual cell. RESULTS: The secretion of IL-2
      was markedly low in the demented patients, compared with both elderly and middle
      aged subjects. IL-1beta and TNFalpha production was similar in the individuals of
      the 3 groups. The production of IL-6 and IL-10 was significantly lower when
      compared to that of the middle-aged, but did not differ between the elderly
      patients with and without dementia. The phagocytic function of both
      polymorphonuclear cells and monocytes was decreased in individuals of the elderly
      groups with a low number of engulfed latex particles by each individual
      polymorphonuclear cell. The production of superoxide anions was increased only by
      monocytes from the elderly groups. CONCLUSIONS: The results suggest that although
      the impaired immune function in patients with Alzheimer's disease is related to
      the aging process, the significant low IL-2 production in these patients may play
      a role in their increased susceptibility to infections.

PMID- 11961365
TI  - Cardiovascular responses to lower body negative pressure in the elderly: role of
      reduced leg compliance.
AB  - BACKGROUND: It is warranted to test the hypothesis that the orthostatic tolerance
      does not diminish in the aging process per se in healthy individuals. OBJECTIVE:
      The purpose of the present study was to examine the effects of aging on
      cardiovascular response and baroreflex sensitivity during lower body negative
      pressure (LBNP) with a special reference to leg compliance. METHODS: Fifteen
      healthy old male subjects [mean age 68.2 +/- (SE) 0.8 years] and 22 young male
      subjects [mean age 21.4 +/- (SE) 0.3 years] underwent a 21-min bout of ramped
      LBNP (from 0 to -60 mm Hg, 10 mm Hg each for 3 min). Heart rate (HR), blood
      pressure, stroke volume (SV), forearm blood flow, and leg volume were measured
      throughout the experimental period. The arterial baroreflex sensitivity was
      calculated from spontaneous changes in beat-to-beat arterial pressure and HR
      during LBNP. RESULTS: The leg compliance was lower, and the orthostatic tolerance
      index was higher in old than in young participants. The LBNP-associated increases
      in leg volume and HR and the decreases in SV were lower in old subjects,
      suggesting that the reduction of venous return was less in magnitude in old
      subjects during LBNP. The baseline value of baroreflex sensitivity evaluated by
      the sequence analysis was smaller, and no LBNP-related change was observed in old
      subjects, whereas a gradual LBNP-related reduction was observed in young
      subjects. The slope of regression between DeltaSV and change in forearm vascular
      resistance during LBNP was identical in both age groups. CONCLUSIONS: We conclude
      that: (1) aging per se does not increase the intolerance to orthostatic stress
      induced by LBNP; (2) a low magnitude of venous return reduction during LBNP
      contributes to a higher tolerance in the old because of lower leg compliance, and
      (3) the sensitivity of baroreflex control of the HR is attenuated in the old;
      however, there is no deterioration of the sensitivity of the peripheral
      vasoconstriction during LBNP.

PMID- 11961366
TI  - Creatinine clearance, Cockcroft-Gault formula and cystatin C: estimators of true
      glomerular filtration rate in the elderly?
AB  - BACKGROUND: The aim of this study was to assess the accuracy and precision of
      estimators of true glomerular filtration rate (GFR) (Cockcroft formula, measured
      creatinine clearance (CCR) and a cystatin-C-based estimation) in elderly patients
      attending a geriatric department. Additionally, parameters influencing GFR in the
      elderly were evaluated. METHODS: 30 patients aged 57-90 years treated in the
      Geriatric Department for pulmonary or cerebral diseases were included in the
      study. Nine patients were diabetic and 16 hypertensive. Exclusion criteria were
      advanced dementia, acute heart failure and primary renal disease. Inulin
      clearance (CINU), CCR and estimation by Cockcroft-Gault equation (CG) were
      performed on the same day. For comparison of the methods an analysis according to
      Bland and Altman was used, depicting the mean difference between the methods and
      the limits of agreement of the differences, representing their 95% interval of
      confidence. Furthermore, the influence of confounding variables on GFR estimation
      was analyzed by multiple regression. RESULTS: Baseline characteristics showed a
      median age of 74.5 years and a median body weight of 66.7 kg. Median values for
      serum creatinine 88.4 micromol/l, 5.74 mmol/l for urea and 1.57 mg/l for cystatin
      C. CCR (median: 51.6 ml/min) and CG (median: 63.0 ml/min) underestimated CINU
      (median: 83.3 ml/min). Both methods showed poor precision compared with CINU. The
      upper limit of agreement of the difference was 101.3 ml/min for CCR and 81.4
      ml/min for CG, the lower limit was -33.8 ml/min for CCR and -24.6 ml/min for CG.
      Among frequently used variables to predict GFR, the reciprocal of serum
      creatinine and body weight revealed a significant influence but not age or
      gender. A cystatin-C-based estimation of GFR, derived from regression analysis,
      did not improve the precision of the estimation of GFR compared to CG.
      Additionally, the occurrence of diabetes mellitus disclosed a borderline
      influence on the estimation of GFR. CONCLUSION: CCR is not only inconvenient and
      time consuming, but also imprecise and inaccurate in the elderly, mainly due to
      reduced muscle mass and erroneous urine sampling. CG and a cystatin-C-based
      estimation are slightly more adequate, but overall there is no sufficiently
      precise formula for GFR estimation in the elderly.

PMID- 11961367
TI  - Characteristics of single fallers and recurrent fallers among hospital in
      patients.
AB  - BACKGROUND: Recurrent fallers constitute a minority of patients who fall but
      contribute considerably to the total number of falls recorded. OBJECTIVE: To
      study the characteristics of recurrent fallers in a hospital setting. METHODS: In
      a prospective observational study we investigated the characteristics of 1,025
      patients admitted to a geriatric non-acute hospital. Patients were followed until
      discharge and were classified as non-fallers, single fallers or recurrent
      fallers. RESULTS: We identified 824 non-fallers, 136 single fallers and 65
      recurrent fallers contributing 175 falls. Compared to non-fallers, recurrent
      fallers were more likely to have pre-admission falls (p = 0.004), confusion (p <
      0.0001), an unsafe gait (p = 0.0001) and be on tranquillisers (p = 0.018) and
      antidepressants (p = 0.006). They had longer stays in hospital (p < 0.0001) and
      more nursing home discharges (p = 0.0001). There was considerable overlap with
      risk factors for single fallers but compared to this group they were more likely
      to be confused (p = 0.027), and on antidepressant medication (p = 0.009). They
      also had a longer length of stay (p < 0.001) and more nursing home discharges (p
      = 0.03). Confusion (p = 0.0001), unsafe gait (p = 0.0006) and antidepressants (p
      = 0.018) were independently associated with recurrent falls. CONCLUSIONS: It is
      important to recognise the risk factors that prospectively identify a recurrent
      faller because of the significant contribution to total falls by a relatively
      small number of patients. This may be useful not only in trying to reduce total
      falls but also in trying to reduce injury.

PMID- 11961368
TI  - Effects of age on the relationship between drinking and atherosclerotic risk
      factors.
AB  - BACKGROUND: Drinking modulates the progress of atherosclerotic cardiovascular
      diseases by affecting atherosclerotic risk factors. However, age-dependent
      effects of drinking on atherosclerotic risk factors have not been clarified in
      detail. OBJECTIVE: In this cross-sectional study, we investigated whether the
      relationship between drinking and atherosclerotic risk factors is influenced by
      age in male workers (12,386 men aged from 20 to 69 years) in Yamagata, a district
      of Japan. METHODS: The subjects were divided into five age groups, and each group
      was further divided into three subgroups according to ethanol consumption. The
      mean levels of each atherosclerotic risk factor were compared among the groups.
      RESULTS: Neither body mass index nor fasting blood glucose levels were
      significantly affected by drinking at any age. In the heavy drinkers (ethanol
      consumption of 30 g per day or more) in all age groups, blood pressure, serum
      triglyceride and HDL cholesterol levels were significantly higher and serum LDL
      cholesterol level and the atherogenic index were significantly lower than in the
      nondrinkers. In the light drinkers (ethanol consumption of less than 30 g per
      day) in all age groups, serum HDL cholesterol level and the atherogenic index
      were also higher and lower, respectively, than in the nondrinkers. However, light
      drinking significantly increased blood pressure only in the middle aged and
      relatively elderly groups (40-49, 50-59, 60-69 years of age) and significantly
      decreased the serum LDL cholesterol level only in relatively young and middle
      aged groups (30-39, 40-49, 50-59 years of age). Thus, the effects of light
      drinking on blood pressure and serum LDL cholesterol are dependent on age. The
      serum triglyceride level was not significantly affected by light drinking in any
      age group. CONCLUSIONS: Our results suggest that light drinking increases blood
      pressure in the middle-aged and the elderly but not in the young, while its
      beneficial effects on serum HDL cholesterol and atherogenic index are not changed
      with age.

PMID- 11961369
TI  - Positive association between total lymphocyte count and femur bone mineral
      density in hip-fractured women.
AB  - BACKGROUND: Protein depletion appears to play a detrimental role in the causes of
      hip fracture and low bone mineral density has been observed in protein-depleted
      subjects. OBJECTIVE: To investigate the association between femur bone mineral
      density and total lymphocyte count, a marker of the protein nutrition status, in
      elderly hip-fractured women. METHODS: 210 white women affected by their first hip
      fracture either spontaneous or due to minimal trauma consecutively admitted to a
      rehabilitation hospital were studied. 34 women were ruled out because of
      confounding factors altering their lymphocyte count. Both total lymphocyte count
      and bone mineral density at the unfractured femur were evaluated. The correlation
      between these two variables was studied by Pearson's coefficient. Bonferroni
      adjustment was used for multiple comparisons. Bone density was measured by DXA
      (Hologic QDR 4500W). RESULTS: A positive correlation was observed between
      lymphocyte count and bone mineral density measured at both total proximal femur
      (r = 0.21; p < 0.05) and intertrochanteric area (r = 0.21; p < 0.05). Stepwise
      linear multiple regression analysis showed that the association with total
      lymphocyte count was independent of age, weight, height, body mass index, time
      between surgery and blood sample collection for lymphocyte count and type of hip
      fracture (cervical or trochanteric) when bone mineral density was evaluated both
      at total proximal femur (p < 0.05) and intertrochanteric area (p < 0.05).
      CONCLUSION: Our results support the role exerted by protein nutrition in bone
      health, at least in elderly frail women. From this point of view, a total
      lymphocyte count is a suitable, inexpensive marker.

PMID- 11961370
TI  - Usefulness of calf circumference measurement in assessing the nutritional state
      of hospitalized elderly people.
AB  - BACKGROUND: Malnutrition is a widespread but largely unrecognized problem in aged
      patients, more so as it is a contributing factor to the increased morbidity and
      mortality in this age group. Since direct measurements of body composition are
      not possible in a large number of patients, good anthropometric reference data
      are fundamental in assessing the nutritional state of elderly people. OBJECTIVE:
      To examine the efficacy of calf circumference (CC) measurement for assessing the
      nutritional state of the elderly. METHODS: The nutritional state was assessed by
      anthropometric and biological measurements in 911 elderly patients consecutively
      admitted to a geriatric unit. In the first instance, univariate analysis was
      performed for CC and other nutritional parameters. Linear and multiple stepwise
      regressions were performed to study the association between anthropometric or
      biological parameters and CC. At a later stage, the specificity, sensitivity and
      the optimal cutoff CC were established for 2 groups of patients: malnourished and
      controls. Finally, patients were classified according to this cutoff in order to
      verify the efficacy of CC in assessing their nutritional state. RESULTS: The
      results of univariate analysis showed significant correlations between CC and
      other nutritional anthropometric markers (r = 0.706, p < 0.0001 with body mass
      index (BMI) and r = 0.661, p < 0.0001 with fat free mass) and biological markers
      (r = 0.219, p < 0.0001 with albumin and r = 0.162, p < 0.0001 with
      transthyretin). Multiple regression confirmed associations between CC and
      tricipital skinfold thickness (p < 0.0001), fat free mass (p < 0.0001), BMI (p <
      0.0001), and serum albumin (p < 0.0001; r(2) = 0.561). The optimal cutoff for CC
      was found to be 30.5 cm for both men (sensitivity 73.2%, specificity 72.8%) and
      women (sensitivity 78.8%, specificity 61.1%). The classification of patients
      according to this discriminating factor was confirmed for the optimal cutoff
      value. CONCLUSION: Calf circumference is a pertinent marker of nutritional state.
      The cutoff of 30.5 cm provides a good diagnostic capacity.

PMID- 11961371
TI  - Difficulties of recruitment for a randomized controlled trial involving influenza
      vaccination in healthy older people.
AB  - BACKGROUND: In a randomized controlled trial to determine the cost benefits of
      influenza vaccination in fit healthy individuals aged 65-74 years, recruiting
      individuals to the study was more difficult than anticipated. OBJECTIVES: To
      investigate reasons for poor recruitment. MATERIALS AND METHODS: 6,058 people
      were initially identified as eligible for the study but only 729 (12%) were
      subsequently randomized. Individuals (n = 2,583) who returned cards indicating
      that they did not wish to participate were sent a postal questionnaire asking for
      reasons why they felt unable to consent for the study. RESULTS: 1,173/2,583
      (45.4%) questionnaires were returned. A total of 2,621 reasons were given for
      nonparticipation, i.e. a mean of 2.2 reasons per questionnaire returned. Reasons
      given for noninvolvement were: reluctance to participate in a research project
      (53%); concerned about side effects (34%); self-perceived view of not requiring
      influenza vaccination (31.7%); preference for own doctor to give the vaccine
      (29.1%); objection to name "Geriatric Medicine" on the letter of invitation
      (25.2%); already been vaccinated (17.3%); illness requiring vaccination out of
      the study (13.8%); previous bad reaction to the vaccine (6.4%); unable to attend
      on day of vaccination (4.3%); unable to get to general practice surgery (4%);
      already involved in a clinical trial (2.5%); fear of needles/dislike of
      injections (1.6%); doubts about vaccine efficacy (0.3%); egg allergy (0.2%).
      CONCLUSION: Inaccurate beliefs about influenza vaccination persist across a wide
      section of the community. Efforts should be made by all health professionals to
      correct these false beliefs and ensure that those at risk can be easily
      recognized and targeted for vaccination.

PMID- 11961372
TI  - Vasculitis in the very elderly.
AB  - BACKGROUND: Whatever may be their clinical presentation, vasculitis syndromes
      (VS) have a bad prognosis in the very elderly. OBJECTIVE: The aim of this work
      was to study VS particularities in very old people. Most published studies on VS
      in elderly people concern patients older than 60 years; studies concerning very
      old patients are unusual. METHODS: We studied retrospectively subjects older than
      75 years with a diagnosis of VS from the Departments of Geriatrics and Internal
      Medicine at Dijon University Hospital. These subjects were hospitalized between
      January 1995 and December 1999. Data were obtained from the medical files of
      these patients. Several aspects were considered: type of VS, associated diseases,
      treatment, complications, and outcome. RESULTS: Twelve patients, 5 men and 7
      women aged 79-91 (mean age 82.3) years, were included. Primary VS was observed in
      half of the patients and secondary VS in the others. The initial clinical
      presentation was often polymorphous and unspecific; 8 of the patients died, 2
      developed progressive severe functional impairment, 1 was stabilized under
      therapy, and 1 patient with VS secondary to infection recovered. Most patients
      either died quickly or progressively deteriorated from infections, malnutrition,
      or functional impairment. CONCLUSION: The health of the majority of patients
      (83%) deteriorated dramatically, leading to death or severe functional
      impairment.

PMID- 11961373
TI  - On the role of aging in the etiology of autoimmunity.
AB  - Several types of diseases, among others autoimmune illnesses, could be coupled
      with the general processes of aging. The two-edged sword of immune defense is
      directed on one side against environmental attacks and on the other against the
      body itself. However, one has to make a difference between normal (physiological)
      clearance and autoimmune diseases, although both sides of autoimmunity are
      influenced by the general processes of senescence. Aging of the thymus seems to
      be one of the key elements in the etiology of autoimmunity, although other cell
      types and their aging also play a substantial role in this process. Spontaneous
      genetic instability, acquired genetic mutations due to aging and the age-related
      alterations in the information level of the body may together be important
      elements in the pathomechanism of both physiological autoimmunity and autoimmune
      diseases. Nevertheless, physiological autoimmunity seems to be directed mostly by
      natural factors (such as aging and apoptosis) but primary autoimmune diseases may
      be caused by genetic instability that is enhanced by aging as well.

PMID- 11961374
TI  - A comparative study of two psychometric approaches to detect risk status for
      dementia.
AB  - This study results from an effort to examine the relationship between the
      diagnostic potentials for detecting risk status for dementia of a cognitive
      plasticity approach and a traditional status-oriented procedure (test battery) by
      Storandt et al. [Arch Neurol 1984;41:497-499]. The aim is to compare prediction
      accuracy for risk for developing dementia with these two approaches. A sample of
      106 community-dwelling elderly adults were tested with both procedures, and their
      scores on the Structured Interview for the Diagnosis of Dementia used as external
      criterion for predicting risk status. The findings show that figural relations
      pretest and training gains account for a considerable amount of individual
      differences in mental status similar to that explained by the traditional test
      battery. In addition, the accuracy of discrimination between healthy and at-risk
      participants appears slightly higher when using the figural pretest and training
      gains. These results suggest the conclusion that use of figural relations tests
      and the cognitive plasticity approach represents a viable alternative to the
      traditional, status-oriented test battery as a means of early diagnosis of
      dementia in nonclinical populations.

PMID- 11961375
TI  - Sitting position to prevent aspiration in bed-bound patients.

PMID- 11961376
TI  - Regulation of plasma adenosine levels in normal pregnancy.
AB  - The aim of this study was to investigate the possible mechanism of the regulation
      of plasma adenosine concentration [ADO] in normal pregnancy. We measured the
      activities of circulating enzymes that are involved in the production and
      metabolism of adenosine, and plasma [ADO] in nonpregnant (n = 14) and normal
      pregnant women (n = 14) in the third trimester. In pregnant women, the activity
      of plasma 5'-nucleotidase and plasma [ADO] were significantly elevated and plasma
      adenosine deaminase activity was significantly reduced. Enzymatic activities of
      both plasma enzymes appear to be changed in a way that would favor increased
      adenosine concentrations.

PMID- 11961377
TI  - Value of subcutaneous drainage system in obese females undergoing cesarean
      section using pfannenstiel incision.
AB  - OBJECTIVE: To determine whether closed subcutaneous drainage systems were
      efficacious in reducing the rate of wound breakdown of Pfannenstiel incision
      after cesarean section (CS) in obese females. DESIGN: Prospective controlled
      clinical trial. PARTICIPANTS: 118 obese pregnant females with a body mass index
      >32 undergoing CS were divided into two groups: group I (n = 78) with closed
      subcutaneous drainage system and group II (n = 40) without drainage system.
      Incision closure technique was standardized. Prophylactic antibiotics were given
      routinely to both groups. OUTCOME MEASURES: Primary outcomes were the incidence
      of wound breakdown in both groups together with rate of hematoma formation and
      occurrence of fever. Secondary outcomes were amount of fluid drained, need for
      redressing. RESULTS: Wound breakdown occurred in 9 cases in group I (11.5%),
      while it happened in 5 cases in group II (12.5%) (p > 0.05). Relative risk was
      0.92 (95% CI 0.26-3.75). Hematoma formation was observed in only 1 case in the
      nondrainage group (group II). Fever was observed in 18 cases in group I (23.1%)
      in the first 24 h postoperative while in group II, 13 cases developed fever
      (32.5%) (p > 0.05). The need for redressing within the first 24 h was only in
      2.5% of cases in group I while it was 17.9% in group II (p < 0.05). CONCLUSION:
      We found no significant benefit in using a subcutaneous drain as a prophylactic
      measure against wound breakdown in obese pregnant females undergoing CS as long
      as they received a prophylactic antibiotic.

PMID- 11961378
TI  - Can myomectomy be performed during pregnancy?
AB  - OBJECTIVE: To evaluate the effectiveness, safety, complications and outcome of
      pregnancy after myomectomy performed during pregnancy. MATERIAL AND METHODS: Five
      pregnant women with myomas requiring operation because of severe abdominal pain
      were included in the series at the Department of Obstetrics and Gynecology,
      Selcuk University Faculty of Medicine between October 1, 1996 and February 24,
      2001. The patients were controlled with ultrasonography and cardiotocography
      every month up to 32 gestational weeks and then every 2 weeks. Cesarean section
      was performed on all patients at 37-40 weeks. Complications and fetoneonatal
      outcome were recorded. RESULTS: The mean age of the patients was 31.4 +/- 3.5
      years. The mean parity was 1.4 +/- 1.6. The median gestational age at the time of
      myomectomy was 17.8 +/- 3.4 weeks. The mean size of the myomas was 14.0 +/- 3.8
      cm. The main symptom of all patients was severe abdominal pain in spite of
      analgesic medication. The mean duration of the operation was 40.0 +/- 7.9 min.
      The mean blood loss was 280.0 +/- 83.6 ml. The mean number of myomas removed was
      2.8 +/- 1.3. CONCLUSION: Myomectomy during pregnancy can be performed if
      necessary.

PMID- 11961380
TI  - The lunar cycle and the number of deliveries in Austria between 1970 and 1999.
AB  - The effect of the moon on the number of newborns has been investigated
      extensively with contradictory results but with few significant findings. In this
      paper, a possible lunar effect is analyzed by a nonlinear Poisson regression
      model similar to a Fourier analysis based on all children (n = 2,760,362) born in
      Austria between 1970 and 1999, i.e. 371 lunar cycles. We found no significant
      effect even when considering the influence of parity and gestation. Our study is
      in contrast to a French study using a similarly large data base which showed a
      weak but significant effect. Nevertheless, significant p values based on very
      large samples must be interpreted cautiously. Our study is in concordance with
      other studies which often use small and selected samples or rather inefficient
      statistical methods. We conclude that there is no significant effect of the lunar
      cycle on the number of deliveries in Austria.

PMID- 11961379
TI  - Frequency of factor V, prothrombin and methylenetetrahydrofolate reductase gene
      variants in preeclampsia.
AB  - BACKGROUND: The association between thrombophilic variants (Leiden mutation of
      the factor V gene, G20210A mutation of the prothrombin gene and C677T
      polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene) with
      preeclampsia was investigated in a north-eastern Italian population. METHODS:
      Fifty-eight preeclamptic (PE) women and 74 normal pregnancies were evaluated.
      Genotypes were determined by polymerase chain reaction. RESULTS: The frequency of
      heterozygous carriers of the factor V Leiden was similar between PE women (5.2%)
      compared to the control subjects (4.1%; p 0.76). Also the frequencies of G20210A
      and C677T mutations were similar between PE and control subjects. CONCLUSIONS: In
      this population, we found no difference in the prevalence of genetic risk factors
      for thrombosis in women with preeclampsia compared with control subjects.

PMID- 11961381
TI  - Obstetrics and perinatal outcome of adolescent nulliparous pregnant women.
AB  - OBJECTIVE: To study obstetrics and perinatal outcome in nulliparous teenage
      singleton pregnancies at a referral teaching hospital in the eastern province of
      Saudi Arabia. METHOD: All singleton births during 1996-2000 of nulliparous
      mothers aged < or =17 years at King Fahd University Hospital were reviewed (n =
      102) and compared with births of a control group of nulliparous mothers aged 20
      24 years who delivered during the same period (n = 102). RESULTS: The incidence
      of nulliparous teenage pregnancies was 0.8%. As compared with women aged 20-24
      years, women of 17 years or less were at higher risk of very preterm birth (p <
      0.05). The 5-min Apgar scores were not different between the two groups. Babies
      born to younger mothers had a significantly lower birth weight than those born to
      older mothers (p < 0.001); the incidence of a low birth weight (<2,500 g) was
      significantly lower in the control group (p < 0.04). There were no significant
      differences in distribution of mode of delivery, admission to the special care
      baby unit, antenatal complications, cesarean section indications, perinatal
      mortality rate, and early neonatal complications between the two groups.
      CONCLUSION: The increase in the very preterm births and the subsequently lower
      birth weight observed in nulliparous teenage women suggest that the maternal age
      may be a risk factor for very preterm births and associated long-term hazards.

PMID- 11961382
TI  - Effects of ondansetron, granisetron, ramosetron, and azasetron on human
      neutrophil functions.
AB  - Neutrophil functions play an important role in the antibacterial or antitumor
      host defense system. Ondansetron, granisetron, ramosetron, and azasetron are
      often used in gynecological patients as a prophylaxis against postoperative
      emesis or chemotherapy-induced emesis. In this study, using an ex vivo system, we
      have shown that these antiemetics at clinically relevant concentrations had no
      effect on superoxide (O(-)(2)) and hydrogen peroxide (H(2)O(2)) production of
      neutrophils, although high doses of these drugs significantly inhibited it to a
      similar degree. The drugs failed to impair chemotaxis or phagocytosis and to
      scavenge O(-)(2) or H(2)O(2) generated by an acellular system. Inhibition of the
      reactive oxygen species production may be due to attenuation of calcium elevation
      in neutrophils with these antiemetics. Our findings suggest that we are able to
      use these antiemetics in gynecological patients with cancer or those undergoing
      surgery without great caution.

PMID- 11961383
TI  - Prediction of the effect of metformin treatment in patients with polycystic ovary
      syndrome.
AB  - The objective of the study was to find predictors of a successful therapy with
      metformin in polycystic ovary syndrome. 24 women with polycystic ovary syndrome
      were examined (oral glucose tolerance test and gonadotropin-releasing hormone
      analogue test) before and after a 6-month course of metformin (1 g/day). In 58%
      of the women, a significant improvement in the menstrual cycle pattern was
      observed. After a treatment course, a significant reduction in gonadotropin
      releasing hormone analogue stimulated levels of testosterone (p < 0.05), free
      testosterone index (p < 0.01), luteinizing hormone (p < 0.05), and estradiol (p <
      0.01) was found. The best prediction of the improvement in menstrual cyclicity
      after metformin was achieved with a combination of basal values of 17
      hydroxyprogesterone, testosterone, sex hormone binding globulin, and
      androstenedione. These variables correctly classified 86.7% of the responders.
      The best predictor of changes in the index of free testosterone after metformin
      treatment was the combination of estradiol and androstenedione in the
      gonadotropin-releasing hormone analogue test, with basal testosterone correctly
      classifying 91.7% of the subjects.

PMID- 11961384
TI  - Human endometrial epithelial cells modulate the activation of gelatinase a by
      stromal cells.
AB  - Metalloproteinases (MMPs) are central effectors in endometrial physiology. Their
      production is tightly regulated by ovarian steroids and cytokines. Using
      zymography, we investigated MMP-2 production by human endometrial cells treated
      with estradiol-17beta + progesterone (E(2)+P) and by various key cytokines in
      endometrial physiology (IL-1beta, LIF, TGF-beta, and TNF-alpha). No gelatinase
      activity was detected in the culture media of epithelial cells. In basal
      conditions, stromal cells produced the pro form of MMP-2. MMP-2
      production/activation was not directly affected by cytokine treatment.
      Interestingly, activated MMP-2 was only detected after treatment of stromal cells
      with culture medium from epithelial cells. Cytokine treatment of epithelial cells
      increased the capacity of conditioned medium to stimulate stromal cells to
      activate MMP-2. As the tissue inhibitor of MMP-2 (TIMP-2) is a regulator of
      gelatinase A activity, its concentration was measured by ELISA. TIMP-2 production
      by stromal cells was not affected by cytokines or by epithelial cell-conditioned
      medium. These results strongly suggest that regulation of stromal MMP-2
      activation involves soluble factor(s) derived from the epithelial compartment.

PMID- 11961385
TI  - Pure red cell aplasia and acute hepatitis during pregnancy.
AB  - Pure red cell aplasia during pregnancy is rare. We present a case in a 26-year
      old pregnant woman, referred to our hospital at 31 weeks' gestation because of
      severe anemia caused by acute hepatitis. She was treated with repeated blood
      transfusions and the pure red cell aplasia gradually remitted during the
      pregnancy. A live infant was delivered by cesarean section at 34 weeks'
      gestation. Postpartum, the pure red cell aplasia and hemolytic anemia remitted
      completely. Our case illustrates that pure red cell aplasia may occur late in
      pregnancy associated with acute viral hepatitis and is reversible during
      pregnancy without any necessity for steroid therapy.

PMID- 11961386
TI  - Transdermal estradiol in menopausal women depresses interleukin-6 without
      affecting other markers of immune response.
AB  - OBJECTIVE: The aim of this study was to analyze the effect of transdermal
      estradiol replacement therapy (HRT) on immune function in menopausal women. STUDY
      DESIGN: A prospective comparative study was carried out in 30 women, aged 48-55
      years, who were divided into two groups; 20 of them received transdermal
      estradiol 50 microg/day during 3 months and 10 who refused to receive HRT served
      as controls. Serum interleukins were quantified by specific immunoenzymatic
      assays; in addition, hormones of somatotropin axis and prolactin (PRL) were
      quantified by IRMA and RIA. RESULTS: Baseline elevated interleukin (IL)-6 levels
      decreased significantly (p < 0.001) after transdermal HRT as compared with the
      nontreated group. Contrarily, IL-2 and IL-10 levels as well as mitogenic induced
      T-cell proliferation were unchanged under HRT. Insulin-like growth factor-I,
      growth hormone and PRL levels were unaltered by transdermal HRT. CONCLUSION:
      Decrement of IL-6 in parallel with absent effect on some indices of immune
      activity suggests a beneficial action of transdermal HRT. These findings contrast
      with those demonstrating an increment of immune response in women taking oral
      HRT. Thus, the route of administra tion determines the effect of HRT on immune
      function.

PMID- 11961387
TI  - Local erythematous dermatitis after intravenous docetaxel.
AB  - We report the case of a patient who developed a local skin eruption over the vein
      following intravenous infusion of docetaxel at 4-week intervals. The skin lesions
      were limited to an area of the forearm proximal to the site of infusion. They
      appeared 1 week after the infusion and were diagnosed as erythema multiforme
      (mixed-type) based on the histological findings.

PMID- 11961388
TI  - Induction of labor in grand multiparous women and previous cesarean section: is
      it safe?
AB  - OBJECTIVE: To compare the outcome of induced and spontaneous labor in grand
      multiparous women with one previous lower segment cesarean section, so that the
      safety of labor induction could be assessed. METHOD: In 56 women labor was
      induced and their outcomes were compared with those of 177 women with spontaneous
      labor. All women were multiparous and had had one previous cesarean section.
      RESULTS: There were no significant differences in the incidences of 1- and 5-min
      Apgar scores, congenital malformation, cesarean section rates and uterine scar
      dehiscence or uterine rupture. There were 4 cases of intrauterine fetal death in
      the induction group, but no case of intrapartum or early neonatal death in the 2
      groups. In the study group, 80.4% of the women delivered vaginally compared with
      84.3% in the control group. CONCLUSION: In this moderate-sized study, we may
      conclude that when there is no absolute indication for repeating cesarean
      section, induction of labor may be a safe option in these high-risk women.

PMID- 11961389
TI  - Three-dimensional sonographic features of nuchal edema.
AB  - OBJECTIVE: To describe the three-dimensional (3D) sonographic features of nuchal
      edema in the early second trimester of pregnancy. METHODS: From 16 to 22 weeks of
      gestation 5 cases with nuchal edema were studied using transabdominal 3D
      sonography. RESULTS: Nuchal edema could be easily imaged with both two
      dimensional and 3D sonography; however, visualization of the continuity and
      curvature of structures was more easily accomplished with 3D sonography. Before
      20 weeks of gestation, the skin has a transparent structure, so the bony
      structures are clearly identified. 3D sonography allowed visualization of nuchal
      edema in all three dimensions at the same time, providing an improved overview
      and a more clearly defined demonstration of the adjusted anatomical planes.
      CONCLUSION: These results suggest that 3D sonography provides a novel means of
      visualizing nuchal edema in utero.

PMID- 11961390
TI  - Laparoscopic conservation of the ovaries in cases with massive ovarian oedema.
AB  - Two women, one 27 years old (case 1) and the other 20 years old (case 2), were
      evaluated due to right lower quadrant pain. The lactate dehydrogenase level was
      increased in case 1 and the dihydroepiandostrone level was increased in both
      cases. Preoperative transvaginal ultrasonography revealed solid masses, but the
      tumour markers were within normal limits. At laparoscopy, oedematous ovaries were
      diagnosed in both cases. Untwisting of the ovaries and laparoscopic wedge
      resection combined with frozen section analysis resulted in conservation of the
      ovaries in both cases. The patients are symptom-free after 1 year of follow-up.

PMID- 11961391
TI  - Unruptured pelvic abscesses in pregnancy: report of two cases.
AB  - Pelvic abscess is a rare entity in pregnancy. The true etiology is uncertain but
      a flare-up of an old pelvic inflammatory disease is most likely. Usually, these
      patients undergo laparotomy and these abscesses are discovered incidentally, as
      described in our series. Surgical drainage and conservative surgical procedures
      under antibiotics are recommended during pregnancy albeit there is no consensus
      on patient management. Through this report, we aim to discuss this clinical
      entity and to underline the importance of patient management in case of its
      diagnosis.

PMID- 11961392
TI  - Does a failure of crystal inhibition cause calcium renal stones?

PMID- 11961393
TI  - Role of apoptosis in fibrogenesis.

PMID- 11961394
TI  - Role of nitric oxide in inflammatory conditions.
AB  - Nitric oxide (NO) plays an important regulatory/modulatory role in a variety of
      inflammatory conditions. NO is a small, short-lived molecule that is released
      from a variety of cells in response to homeostatic and pathologic stimuli. It may
      act as a vasodilator and a platelet inhibitor and may interfere with adhesion
      molecules to prevent neutrophil adhesion. NO release may also lead to the
      formation of highly reactive species such as peroxynitrite and stable
      nitrosothiols and may cause mitochondrial damage and nitration of protein
      tyrosine residues. In addition, NO inhibits cell proliferation via inhibition of
      polyamine synthesis and cell uptake and may well act as a 'brake' on the
      proliferative response following cytokine exposure. All three isoforms of nitric
      oxide synthases are found in the kidney during inflammation. The site of NO
      release impacts significantly on its net function and structural impact. NO plays
      a protective role in many forms of immune injury, such as nephrotoxic serum
      induced glomerulonephritis, autoimmune tubular interstitital nephritis, and
      experimental allergic encephalomyelitis. NO overproduction in sepsis, after
      cytokine exposure, inducible NO synthase transcription, and local inflammation
      can autoinhibit endothelial NO synthase, leading to selective renal and
      mesenteric vasoconstriction.

PMID- 11961395
TI  - Plasma orexin concentrations in patients on hemodialysis.
AB  - BACKGROUND: Orexins A and B are neuropeptides that regulate feeding behavior and
      are localized exclusively in neurons within and around the lateral hypothalamic
      area. Intracerebroventricular injection of orexin A stimulates food consumption
      in rats. Plasma concentrations of orexins may reflect nutritional states and may
      have clinical significance in patients on hemodialysis. In this study, we
      investigated the relationship between plasma orexin concentrations and
      nutritional states in patients on hemodialysis. METHOD: We measured plasma orexin
      concentrations in patients on hemodialysis (HD group, n = 67), patients with IgA
      nephropathy (n = 10), patients with diabetes mellitus (n = 11) and healthy
      controls (n = 10). We examined the relationships between plasma orexin
      concentrations and nutritional indices. RESULTS: Plasma orexin A concentrations
      were significantly higher in the HD group than in the control group and showed a
      significant correlation with serum creatinine. In all subjects, there was a
      positive correlation between the plasma orexin A concentration and the serum
      creatinine concentration, but there were no correlations between these
      concentrations in each group. In the HD group, plasma orexin A concentrations had
      a significant positive correlation with the serum albumin concentration and
      percent creatinine generation rate (%CGR). Multiple regression analysis
      demonstrated that %CGR was the only independent factor associated with plasma
      orexin A concentrations. CONCLUSION: Plasma orexin A concentrations are increased
      in patients on hemodialysis. It is possible that the kidney plays a major role in
      the clearance of orexins. The plasma orexin A concentration is significantly
      correlated with %CGR, and it may be able to be used as a clinical marker of the
      nutritional state in patients on hemodialysis.

PMID- 11961396
TI  - Clinical effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension
      in hemodialysis patients.
AB  - Orthostatic hypotension is one of the major factors interfering with everyday
      activities in hemodialysis patients, but there has been no effective agent for
      treating it. In order to clarify the clinical effects of L-threo-3,4
      dihydroxyphenylserine (L-DOPS) on orthostatic hypotension of hemodialysis
      patients, we conducted a randomized, double-blind comparative trial. 149 regular
      hemodialysis patients with orthostatic hypotension were randomly allocated to
      three groups and L-DOPS at doses of 400 mg, 200 mg or placebo was orally
      administrated to each group 30 min before starting every hemodialysis for 4
      weeks. Changes of blood pressure (BP) in orthostatic hypotension immediately
      after completion of hemodialysis and symptoms related to orthostatic hypotension
      were compared between the three groups. In the 400-mg group, systolic and
      diastolic BP after standing increased significantly and the drop of mean BP after
      standing was also reduced compared with pretreatment levels. No such changes were
      observed in the placebo group. Fatiguability, malaise/weakness, dizziness and
      light-headed feeling, the interdialytic symptoms commonly observed in
      hemodialysis patients who developed orthostatic hypotension, were improved to a
      significant extent in the L-DOPS group compared with the placebo group. In
      particular, the improvement was more remarkable for the L-DOPS 400-mg group than
      the placebo group in patients with diabetic nephropathy, lower systolic BP after
      standing, and the long duration type of orthostatic hypotension. The incidence of
      adverse events was comparable between the three groups, and all recovered after
      discontinuation of L-DOPS or concomitantly administered drugs, or without any
      treatment. These findings indicate that L-DOPS taken before hemodialysis prevents
      orthostatic hypotension in patients undergoing hemodialysis, and is also
      effective for the interdialytic symptoms related to orthostatic hypotension.

PMID- 11961397
TI  - Platelet GPIIb/IIIa is activated and platelet-leukocyte coaggregates formed in
      vivo during hemodialysis.
AB  - BACKGROUND/AIM: During hemodialysis, platelets and leukocytes are activated and
      form platelet-leukocyte coaggregates in which GPIIb/IIIa (CD41/CD61) and CD62P (P
      selectin) are involved. However, it is still controversial whether platelet
      activation and platelet-leukocyte coaggregate formation are dependent on the
      dialyzer membrane material. METHOD: We examined the appearance of activation
      dependent antibody on platelets as an index of platelet activation, and the
      appearance of platelet-specific antigen on leukocytes as an index of platelet
      leukocyte coaggregation, during hemodialysis in 7 patients treated using
      regenerated cellulose (RC) membrane and next using polysulfone (PS) membrane. In
      order to reduce the influence of factors other than dialyzer membrane material,
      this study was conducted in a prospective crossover fashion using a pyrogen-free
      bicarbonate dialysate. Moreover, flow cytometric techniques with whole blood were
      employed, which reduce artificial cell activation during the cell or plasma
      separation procedure. The platelet-specific monoclonal antibodies used in this
      study were anti-CD61, PAC-1 (which recognizes only the conformationally activated
      GPIIb/IIIa) and anti-CD62P. RESULTS: Changes in the percentage of PAC-1-positive
      platelets were significantly greater during hemodialysis with RC than with PS.
      However, changes in the percentage of CD62P-positive platelets were not
      significantly different between hemodialysis with RC and PS. Changes in the
      percentage of CD61- or CD62P-positive leukocytes were significantly greater
      during hemodialysis with RC than with PS. Although changes in percentage of PAC-1
      positive platelets did not parallel those of CD62P-positive platelets during
      hemodialysis, there was a significant positive correlation between the percentage
      of CD61-positive leukocytes and the percentage of CD62P-positive leukocytes.
      CONCLUSION: This study, conducted in a prospective crossover fashion using a
      pyrogen-free bicarbonate dialysate in order to reduce the influence of factors
      other than the dialyzer membrane material, demonstrated that both the degrees of
      GPIIb/IIIa activation and platelet-leukocyte coaggregation were greater during
      hemodialysis with RC than PS.

PMID- 11961398
TI  - Marked increases in macrophage colony-stimulating factor and interleukin-18 in
      maintenance hemodialysis patients: comparative study of advanced glycation end
      products, carboxymethyllysine and pentosidine.
AB  - BACKGROUND: Recent studies have demonstrated the crucial involvement of advanced
      glycation end products (AGEs) in major complications of long-term hemodialysis
      (HD) patients. HD, in a clinical setting, is characterized by increased
      production of proinflammatory cytokines. AGEs and cytokines are presumed to be
      responsible for the development of major complications in long-term HD. We
      therefore investigate here the relationship between a newly identified cytokine,
      interleukin-18 (IL-18), and two AGEs, carboxymethyllysine-hemoglobin (CML-Hb) and
      pentosidine. METHODS: CML-Hb, pentosidine macrophage colony-stimulating factor (M
      CSF), and IL-18 were evaluated in 35 patients undergoing stable maintenance HD.
      CML-Hb and pentosidine were measured by a dot blot and competitive ELISA.
      Cytokines were measured with a cytokine-specific ELISA. RESULTS: Circulating
      levels of CML-Hb and pentosidine were elevated in HD patients as compared to
      controls. The serum values of M-CSF and IL-18 were significantly increased in the
      HD patients in comparison to controls. Moreover, these two AGEs and serum values
      of M-CSF, M-CSF and IL-18 showed significant correlation by simple and multiple
      regression analysis. CONCLUSION: Elevation of circulating IL-18 levels was
      demonstrated in maintenance HD patients relative to controls. A correlative
      increase in M-CSF and IL-18 suggests the presence of a primed state of
      monocytes/macrophages in HD patients.

PMID- 11961399
TI  - Acute renal failure in bone marrow transplant patients admitted to the intensive
      care unit.
AB  - BACKGROUND/AIMS: Review of bone marrow transplant (BMT) cases admitted to our
      intensive care unit (ICU) and to compare co-morbidity and outcome of BMT patients
      developing or not developing acute renal failure (ARF). METHODS: A case review of
      BMT patients admitted to the ICU (a 16-bed medico-surgical ICU in a tertiary care
      teaching institution) over a 4-year period. RESULTS: Between January 1994 and
      December 1998, 57 among 441 BMT patients (12.9%) were admitted to the ICU, mainly
      for respiratory distress (58%) and hypotension (32%). Forty-two patients (73.7%)
      presented ARF as defined as a doubling of serum creatinine. Compared to the 15
      other patients, ARF patients had a higher APACHE II score (30 +/- 8 vs. 25 +/- 7,
      p < 0.05). For ARF vs. non-ARF patients, there was no difference in age (43.8 +/-
      10.8 vs. 44.3 +/- 11.1 years), in requirement for mechanical ventilation (76 vs.
      73%) and vasopressors (69 vs. 60%), and in prevalence of graft-versus-host
      disease (19 vs. 13%) or neutropenia (69 vs. 67%), but the prevalence of sepsis
      (83 vs. 60%) and liver failure (69 vs. 40%) was higher. Maximum serum bilirubin
      was markedly increased in ARF compared to non-ARF patients (p < 0.005). For both
      subgroups, no difference in the administration of potential nephrotoxic agents
      was identified. Usually, ARF was considered multifactorial by clinicians, with
      ATN being the most frequent diagnosis (55%). Maximum serum creatinine reached a
      mean of 330 +/- 130 micromol/l. In 74% of cases, ARF occurred concomitantly or
      after admission to the ICU. Oligoanuria was present in 38%, whereas polyuria was
      observed in 17%. Fourteen ARF patients (33%) required dialytic support. Mortality
      rates were significantly different in ARF vs. non-ARF patients (88 vs. 60%, p <
      0.05). Predictive factors for the development of ARF were liver failure (odds
      ratio (OR) 5.9), low serum albumin (OR 1.2) and APACHE II score (OR 1.1), whereas
      variables predictive of mortality were mechanical ventilation (OR 14.8), ARF (OR
      5.8), liver failure (OR 3.7), and APACHE II score (OR 1.2). CONCLUSIONS: This
      study confirms that ARF in BMT patients admitted to the ICU is frequent,
      multifactorial, related to liver failure, and that its development has a negative
      impact on outcome.

PMID- 11961400
TI  - Clinical effect of intravenous calcitriol administration on secondary
      hyperparathyroidism. A double-blind study among 4 doses.
AB  - BACKGROUND/AIMS: Although the PTH-suppressive effect of intravenous calcitriol
      has already been demonstrated by various studies, the precise dose-response to
      calcitriol has not been fully determined for uremic secondary hyperparathyroidism
      (2HPT). In order to investigate in detail the dose-response of intravenous
      calcitriol and the adequate initial dose against 2HPT, a randomized prospective
      double-blind study was conducted. METHOD: One-hundred and sixty-two patients with
      2HPT undergoing hemodialysis three times per week were randomly assigned to four
      calcitriol (Ro21-5535) treatment groups, 0 (placebo), 1, 1.5 or 2 microg.
      Calcitriol or placebo was given intravenously after each dialysis for 12 weeks
      under double-blind conditions. RESULTS: Calcitriol dose-dependently reduced both
      intact-PTH and high-sensitivity assay mid-terminal (HS)-PTH levels. The rate of
      per-week change in intact-PTH was 0.0% in the placebo group, -7.8% in the 1
      microg group, -18.9% in the 1.5-microg group and -24.1% in the 2-microg group.
      Calcitriol dose-dependently increased the rate of increase in serum Ca adjusted
      by albumin level. The per-week increases in adjusted serum Ca were -0.01, 0.08,
      0.23 and 0.35 mg/dl in the placebo, 1-, 1.5- and 2-microg groups, respectively.
      Although the degree of PTH suppression was correlated with the adjusted serum Ca
      increase, by-patients investigation revealed that the number of patients with
      suppression of PTH despite of no or slight elevation of adjusted serum Ca level
      was largest in the 1-microg group among the three calcitriol groups. CONCLUSION:
      Intravenous calcitriol was found to have a clear dose-dependent effect on PTH
      reduction in patients with 2HPT, and the appropriate initial dose of this agent
      was determined to be 1 microg per dialysis session.

PMID- 11961401
TI  - Urinary retinol-binding protein as a prognostic marker in glomerulopathies.
AB  - Tubulointerstitial involvement seems to have a decisive influence on the
      progression of glomerular diseases. We have prospectively evaluated the levels of
      urinary retinol-binding protein (urRBP), a marker of proximal tubular
      dysfunction, in patients with different glomerulopathies (GPs) and correlated
      these levels with disease progression. By studying 238 patients with GPs, we
      found that urRBP tend to be lower in minimal change disease, glomerular hematuria
      and poststreptococcal glomerulonephritis as compared to focal segmental
      glomerulosclerosis, membranous nephropathy and membranoproliferative
      glomerulonephritis. By following 149 patients for up to 10 years, we have
      concluded that high levels of urRBP can identify patients who will progress with
      loss of renal function (defined as doubling of serum creatinine level) and that a
      urRBP level >1 mg/l was an efficient and independent indicator of poor prognosis
      as shown by multivariate analysis. This prediction was possible at a time when
      serum creatinine and creatinine clearance were still in the normal range. Our
      data suggest that this laboratory test adds important clinical information to the
      follow-up of GPs.

PMID- 11961402
TI  - The product of duration and amount of proteinuria (proteinuria index) is a
      possible marker for glomerular and tubulointerstitial damage in IgA nephropathy.
AB  - BACKGROUND/AIMS: IgA nephropathy (IgAN) is one of the major causes for chronic
      renal failure (CRF). Presence of massive proteinuria, hypertension, increased
      serum creatinine level and sclerotic histopathological changes of the glomerulus
      are known to be determinants for the progression of CRF. However, the
      relationships between duration of proteinuria/hematuria and histopathological
      changes, which may be correlated with the renal prognosis, have not been
      clarified. METHODS: A cross-sectional, univariate analysis of clinical parameters
      on the four glomerular and three tubulointerstitial histopathological grades in
      57 untreated biopsy-proven IgAN patients (M/F = 32/25) was performed. RESULTS:
      The age at the time of renal biopsy (35.2 +/- 13.0 years; mean +/- SD), average
      duration of proteinuria (5.3 +/- 5.8 years), mean urinary protein excretion (0.99
      +/- 1.22 g/day), serum creatinine (Cr 0.97 +/- 0.28 mg/dl), Cr clearance (Ccr
      75.5 +/- 29.4 ml/min), and blood urea nitrogen (BUN 15.4 +/- 3.9 mg/dl) were well
      correlated with both histopathological grades. The product of duration (years)
      and urinary protein excretion (g/day) at the time of renal biopsy was more
      significantly correlated with glomerular and tubulointerstitial histopathological
      grades and serum Cr. CONCLUSION: The natural course of IgAN is steadily
      progressive depending on the duration and amount of proteinuria. The product of
      these two factors (proteinuria index) may be a useful predictor for glomerular
      and interstitial histopathological changes and the fate of renal function in
      IgAN.

PMID- 11961403
TI  - The presence and prognostic importance of glomerular macrophage infiltration in
      renal allografts.
AB  - AIM: The purpose of this study was to analyze the role of intraglomerular
      macrophage infiltration in human renal allografts by examining biopsies from
      kidney grafts that were dysfunctional after transplantation. METHODS: Eighty
      three patients (58 men, 25 women) of a mean age of 30.2 +/- 1.4 years were
      evaluated. In all cases, biopsy specimens were examined for the presence of
      macrophage infiltration in the glomeruli. The infiltration of these cells was
      evaluated immunohistochemically using monoclonal antibody CD68, which labels
      macrophage cytoplasm. 10 renal allograft biopsies with normal histopathology were
      used as control group. The CD68-positive macrophages in all glomeruli were
      counted and the glomerular macrophage index (GMI) was calculated. RESULTS: Of the
      83 patients, 40 showed acute rejection (AR), 33 showed chronic rejection (CR) and
      10 showed cyclosporin A (CsA) toxicity. Only the biopsies of 28 patients stained
      positive for CD68 in the glomeruli. Neither patients with CsA toxicity nor
      controls showed intraglomerular macrophages. The CD68-positive group consisted of
      7/33 CR and 21/40 AR patients. We observed intraglomerular macrophages in only 6
      of the 20 AR cases that responded to steroid therapy (mean GMI 0.3 +/- 0.1) and
      in 15 of the 20 steroid-resistant AR cases (mean GMI 1.7 +/- 1.2; p < 0.01). The
      outcome of grafts that contained intraglomerular macrophages was significantly
      worse than the outcomes of other grafts noticed during the follow-up. CONCLUSION:
      We conclude that the presence of glomerular macrophages can be considered a
      marker for rejection and is a valuable additional criterion of rejection in the
      histological examination of renal allograft biopsies. The presence of
      intraglomerular macrophages indicates that the outcome of the graft will be
      significantly worse than that of grafts without intraglomerular macrophage
      infiltration.

PMID- 11961404
TI  - Exogenous nitric oxide inhibits VCAM-1 expression in human peritoneal mesothelial
      cells. Role of cyclic GMP and NF-kappaB.
AB  - Leukocyte adhesion to mesothelium is an important step during peritonitis, which
      is mediated by adhesion molecules including vascular cell adhesion molecule-1
      (VCAM-1). We investigated the effect of exogenous nitric oxide (NO) on VCAM-1
      expression in cultured human peritoneal mesothelial cells and its signal
      transduction pathway. Mesothelial cells were exposed to tumor necrosis factor
      alpha (TNF-alpha) in the presence or absence of NO donors, 3-morpholino
      sydnonimine (SIN-1) and nitroprusside (NP). VCAM-1 mRNA and protein expression
      were measured by Northern blot analysis and flow cytometry. Nuclear factor-kappaB
      (NF-kappaB) binding activity was determined by electrophoretic mobility shift
      assay. Both SIN-1 and NP inhibited the TNF-alpha induced VCAM-1 mRNA expression
      in a dose dependent manner (0.25-2 mM). SIN-1 also suppressed the cell surface
      expression of VCAM-1 molecule. Furthermore, SIN-1 and NP inhibited the VCAM-1
      mRNA expression induced by interleukin-1beta or lipopolysaccharide as well. NF
      kappaB inhibitor, PDTC dose dependently inhibited the TNF-alpha induced VCAM-1
      mRNA expression. SIN-1 inhibited the TNF-alpha- induced NF-kappaB binding
      activity. Analogue of cGMP (8-bromo-cGMP) had no significant effect on TNF-alpha
      induced VCAM-1 mRNA expression and guanylate cyclase inhibitor (ODQ) also had no
      significant influence on the inhibitory effect of SIN-1. These results suggest
      that exogenous NO inhibits VCAM-1 expression via suppression of NF-kappaB through
      a cGMP-independent pathway.

PMID- 11961405
TI  - A new point mutation in the COL4A5 gene described in a Spanish family with X
      linked Alport syndrome.
AB  - BACKGROUND/AIM: Alport syndrome is a hereditary glomerulonephritis, X-linked in
      85% of the cases. This form is associated with mutations in the COL4A5 gene which
      encodes the alpha5 chain of type IV collagen. We have performed the mutational
      analysis of the COL4A5 gene in a Spanish family with X-linked Alport syndrome.
      METHODS: We have analyzed three polymorphic markers close to the gene to confirm
      the X chromosome linkage. By means of the PCR technique, we have screened the 51
      exons of the gene. RESULTS: The segregation of the alleles from the analyzed
      markers was in agreement with the X linkage. Direct sequencing of PCR-amplified
      products has shown a CCT-to-CTT change in exon 25, resulting in substitution of a
      proline for a leucine at position 619 of the polypeptide chain (nucleotide 2058).
      CONCLUSIONS: Although proline is considered a nonconserved amino acid, it is
      essential, upon hydroxylation, in the maintenance of a stable alpha chain triple
      helix collagen. Furthermore, the change cosegregates with the disease in all
      affected members of the family, not being present in 80 control chromosomes. This
      represents a new mutation in the COL4A5 gene found in the Spanish population.

PMID- 11961406
TI  - Sustained expression of thrombospondin-1 is associated with the development of
      glomerular and tubulointerstitial fibrosis in the remnant kidney model.
AB  - BACKGROUND/AIMS: Transforming growth factor-beta1 (TGF-beta1) has been implicated
      in the development of progressive nephrosclerosis in the remnant kidney model of
      chronic renal insufficiency. Thrombospondin-1 (TSP-1) is an extracellular matrix
      protein which has been recently shown to be capable of converting TGF-beta from
      its latent to its active form. We studied the expression of TSP-1 mRNA and
      protein during the development of glomerular and tubulointerstitial
      nephrosclerosis in the renal ablation model particularly in relation to TGF-beta1
      expression. METHODS: The remnant kidney model in the rat was investigated 3 days,
      1 week, 2 weeks, 3 weeks, 4 weeks, 7.5 weeks and 10 weeks after disease
      induction. Using single and double immunostaining techniques, renal tissues were
      examined for TSP-1 protein, TGF-beta1, platelet-derived growth factor BB,
      extracellular matrix proteins, such as collagens and fibronectin, myofibroblast
      formation and macrophage influx. TSP-1 mRNA expression was investigated using a
      radioactive in situ hybridization technique. RESULTS: De novo expression of TSP-1
      mRNA and protein occurred in all glomerular cell types as well as in tubular
      cells, myofibroblasts and some macrophages in areas of tubulointerstitial injury.
      TSP-1 expression preceded and was sustained during the development of
      tubulointerstitial and glomerular fibrosis and was frequently localized at sites
      of increased expression of TGF-beta1, but not of platelet-derived growth factor
      BB. CONCLUSION: In the remnant kidney model, the time course and localization of
      TSP-1 are consistent with its playing a role as a local activator of TGF-beta1,
      thereby potentially participating in the development of nephrosclerosis.

PMID- 11961407
TI  - GLEPP1 receptor tyrosine phosphatase (Ptpro) in rat PAN nephrosis. A marker of
      acute podocyte injury.
AB  - Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein
      tyrosine phosphatase located on the apical cell membrane of visceral glomerular
      epithelial cell and foot processes. This receptor plays a role in regulating the
      structure and function of podocyte foot process. To better understand the utility
      of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1
      protein and mRNA were examined by immunohistochemistry, Western blot and RNase
      protection assay in a model of podocyte injury in the rat. Puromycin
      aminonucleoside nephrosis was induced by single intraperitoneal injection of
      puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7,
      11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute
      phase of proteinuria associated with foot process effacement (days 5-11) and the
      chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At
      day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6
      x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6)
      moles/glomerulus, p < 0.005). This occurred in association with an increase in
      urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In
      contrast, podocalyxin did not change significantly at this time. By day 11,
      GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a
      time when glomerular scarring was present, GLEPP1 was absent from
      glomerulosclerotic areas although the total glomerular content of GLEPP1 was not
      different from normal. We conclude that GLEPP1 expression, unlike podocalyxin,
      reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker
      of podocyte injury.

PMID- 11961408
TI  - Angiotensin II enhances glomerular expression of a nonmuscle myosin heavy chain,
      SMemb, with extracellular matrix accumulation.
AB  - BACKGROUND/AIMS: We previously showed that the mesangial expression of nonmuscle
      type myosin heavy chain, SMemb, was related to glomerular sclerosis. Although
      angiotensin II (AII) is known to promote the glomerular accumulation of
      extracellular matrix and sclerosis, the effect of AII on the mesangial expression
      of SMemb is unknown. Thus, we investigated the effect of AII on the mesangial
      expression of SMemb and synthesis of fibronectin. METHODS: We continuously
      administered AII to Sprague-Dawley rats with subcutaneous osmotic minipumps for
      14 days. Control animals received normal saline instead. The effects of oral
      administration of an AII type 1 (AT1) receptor antagonist, candesartan cilexetil,
      and a vasodilator, hydralazine, were also examined. RESULTS: Semiquantitative
      immunohistochemical evaluation and Western blot analysis showed that AII
      significantly enhanced glomerular expression of SMemb (0.87 +/- 0.33 vs. 0.40 +/-
      0.19 for immunohistochemical grading, p < 0.05; 2.55 +/- 0.88 vs. 1.16 +/- 0.75
      for Western blot analysis, p < 0.05). Glomerular fibronectin was also increased
      in AII-administered rats (301.7 +/- 206.8 ng/5 microg protein vs. 95.8 +/- 81.3
      ng/5 microg protein, p < 0.05). Candesartan cilexetil attenuated these effects.
      On the other hand, hydralazine did not change the glomerular expression of SMemb
      enhanced by AII administration. CONCLUSION: All induced a phenotypic alteration
      in mesangial cells, enhanced the mesangial expression of SMemb and stimulated the
      fibronectin synthesis. These results suggest that the mesangial expression of
      SMemb is related to glomerular matrix accumulation and that AII mediates both
      mesangial processes via AT1 receptors.

PMID- 11961409
TI  - Glomerular cell replication and cell loss through apoptosis in experimental
      diabetes mellitus.
AB  - AIM: To evaluate changes in the glomerular cell balance between replication and
      apoptosis in experimental diabetes mellitus (DM) in relation to morphometric
      data. METHODS: Adult Sprague-Dowley rats with streptozotocin-induced DM and
      controls of the same age and strain were sacrificed 4 and 8 weeks and 6 months
      after disease onset. Cell replication was demonstrated with MIB-5, and apoptosis
      with the terminal uridine nick end labeling technique. Glomerular size and
      glomerular cell population were estimated morphologically. RESULTS: Diabetic and
      control rats showed irrelevant MIB-5 positivity at all time points. Glomerular
      apoptosis was minimal in rats with 4 and 8 weeks of DM and in controls. Rats with
      6 months of DM showed significantly higher glomerular apoptosis values than
      controls (2.49 +/- 0.25 vs. 0.65 +/- 0.16%; p < 0.001). The mean cell count per
      glomerular profile was significantly lower in these diabetic rats (64.02 +/- 1.93
      vs. 78.27 +/- 0.99; p < 0.001), a change that correlated with that in apoptosis.
      The glomerular cell density was further decreased in diabetic rats because of the
      diabetic increase in mean glomerular volume (1.598 vs. 0.927 10(6) microm).
      CONCLUSIONS: Apoptosis is associated with loss of glomerular cells in rats with
      long-term, streptozotocin-induced DM and - to a considerably lower degree - in
      controls of the same age and strain. These changes could be relevant to
      glomerulosclerosis associated with long-term, streptozotocin-induced DM.

PMID- 11961410
TI  - Hyperthermia preconditioning induces renal heat shock protein expression,
      improves cold ischemia tolerance, kidney graft function and survival in rats.
AB  - BACKGROUND: Evidence indicates that hyperthermia preconditioning (HP) can be
      protective in kidney transplantation, possibly through increased heat shock
      protein (HSP) expression. A detailed study about individual HSPs and functional
      preservation is lacking, however. Therefore, we studied the effects of HP on
      kidney graft survival, function and HSP expression. METHODS: Male Lewis rats were
      or were not subjected to whole-body hyperthermia 24 h prior to kidney
      procurement. Kidneys were stored in UW solution at 4 degrees C for 32, 40 or 45
      h. Recipient kidneys were both removed and single isografts transplanted
      orthotopically. RESULTS: HP strongly induced HSP72 and HSP32 expression.
      Following 32-hour cold ischemia, most animals survived even without prior HP.
      However, HP strongly reduced functional impairment induced by cold ischemia.
      Following 40-hour cold ischemia, kidneys from donors without HP did not recover
      function and all animals died within 3 days. In contrast, HP-exposed kidneys
      tolerated 40-hour storage significantly better, with 44% of rats surviving until
      sacrifice on day 7. In these animals, renal function was still better compared to
      animals with 32-hour-stored kidneys without HP. Histological alterations were
      also diminished following HP. CONCLUSION: Our data show that HP induces renal
      HSP72 and, for the first time, HSP32. HP increases survival following
      transplantation and acts by improving several parameters of kidney function
      including proteinuria, volume output and creatinine clearance.

PMID- 11961411
TI  - Minimal change nephrotic syndrome developing during postoperative interferon-beta
      therapy for malignant melanoma.
AB  - A 64-year-old man presented with proteinuria during postoperative interferon
      (IFN)-beta therapy against malignant melanoma. Renal pathologic findings were
      consistent with minimal change nephrotic syndrome (MCNS) showing extensive foot
      process effacement of visceral glomerular epithelial cells (podocyte). Nephrotic
      range proteinuria gradually regressed after stoppage of local injection of IFN
      beta without glucocorticoid treatment. To our knowledge this is the first report
      that demonstrates histological abnormalities of the glomerulus associated with
      postoperative IFN-beta therapy for the malignant melanoma.

PMID- 11961412
TI  - Bismuth subcitrate nephrotoxicity. A reversible cause of acute oliguric renal
      failure.
AB  - Bismuth subcitrate is a known nephrotoxic agent that may lead to acute oliguric
      renal failure when ingested in toxic doses. We report a 17-year-old girl who was
      admitted to the emergency room with complaints of nausea, vomiting, and anuria.
      She had taken 25 tablets containing 300 mg bismuth subcitrate (total 7.5 g). The
      patient was managed with hemodialysis started a week after ingestion. Bismuth
      subcitrate nephrotoxicity should be considered in the differential diagnosis of
      acute renal failure.

PMID- 11961413
TI  - Increased serum levels of interleukin-12 may be associated with Th1
      differentiation in hemodialysis patients.

PMID- 11961414
TI  - Recovering from hepatorenal syndrome: reversibility of renal vasospasm
      demonstrated by Doppler ultrasound.

PMID- 11961415
TI  - Urea kinetics on 8-hour hemodialysis: the third slope meaning.

PMID- 11961416
TI  - Intradialytic amino acid supplementation.

PMID- 11961417
TI  - Brain atrophy in uremia: its underevaluated meaning and consequences.

PMID- 11961418
TI  - The relationship between vowel and consonant duration in Orkney and Shetland
      dialects.
AB  - In Shetland dialect, the northernmost branch of Lowland Scots, stressed
      monosyllables, when closed by a consonant, generally contain either a
      durationally short vowel followed by a durationally long consonant, or a long
      vowel followed by a short consonant. This feature, first described in the 1950s,
      can most likely be ascribed to the Scandinavian substratum of the dialect.
      Although several experimental investigations into the duration of Scottish vowels
      have been carried out recently, most of them in the light of the Scottish vowel
      length rule, none of them so far have looked at Shetland dialect or the
      relationship between the duration of the vowel and the final consonant. In the
      present study we will examine vowel and final consonant duration in monosyllabic
      words in both Shetland and Orkney dialects, as well as in Standard Scottish
      English and Standard Norwegian, in order to establish whether in Shetland
      dialect, durationally short consonants follow durationally long vowels and vice
      versa and if so, if this is indeed a feature peculiar to Shetland.

PMID- 11961419
TI  - Voiceless consonants and locus equations: a comparison with electropalatographic
      data on coarticulation.
AB  - The appropriateness of using locus equations in a study of voiceless consonants
      is examined. The consonants investigated are the stops /t k/ and the fricatives
      /theta s integral/. The slope value of the locus equation, indicating degree of
      coarticulation in the CV syllable, is compared with electropalatographic (EPG)
      data on coarticulation. It is shown that, overall, there is a very poor
      correlation between locus equation and EPG data as regards coarticulation. It is
      also shown that more accurate locus equation results - in terms of their
      correlation with EPG data - are obtained for stop consonants when F2 onset is
      sampled at stop release, rather than at the onset of voicing for the vowel.
      Finally, results for the voiceless consonants are compared with results for their
      homorganic voiced counterparts. Whilst there is no significant difference between
      voiced and voiceless consonants in the EPG data, there is a significant
      difference between voiced and voiceless consonants in the locus equation data.
      These results suggest that locus equations cannot provide invariant cues for stop
      and fricative place of articulation across the voiced-voiceless distinction.

PMID- 11961420
TI  - An x-ray investigation of pharyngeal constriction in American English schwa.
AB  - A study of early X-ray footage of 4 subjects was conducted to test the prediction
      that there may be a midpharyngeal constriction in American English schwa. Results
      show a significant constriction during schwa relative to lingual rest position
      for all 4 speakers. This evidence contradicts views of American English schwa as
      having no articulatory target or place features, as well as those which have
      suggested a neutral target throughout the vocal tract. These findings, however,
      support claims connecting English schwa with reduced /r/. In addition to the
      basic effect 1 subject showed a bimodal pattern in schwa, which may indicate that
      this subject has distinct schwas in lexical vs. functional words, a property that
      has also been observed with respect to /r/ in r-vocalizing dialects.

PMID- 11961421
TI  - The production of english vowels by fluent early and late Italian-English
      bilinguals.
AB  - The primary aim of this study was to determine if fluent early bilinguals who are
      highly experienced in their second language (L2) can produce L2 vowels in a way
      that is indistinguishable from native speakers' vowels. The subjects were native
      speakers of Italian who began learning English when they immigrated to Canada as
      children or adults ('early' vs. 'late' bilinguals). The early bilinguals were
      subdivided into groups differing in amount of continued L1 use (early-low vs.
      early-high). In experiment 1, native English-speaking listeners rated 11 English
      vowels for goodness. As expected, the late bilinguals' vowels received
      significantly lower ratings than the early bilinguals' vowels did. Some of the
      early-high subjects' vowels received lower ratings than vowels spoken by a group
      of native English (NE) speakers, whereas none of the early-low subjects' vowels
      differed from the NE subjects' vowels. Most of the observed differences between
      the NE and early-high groups were for vowels spoken in a nonword condition. The
      results of experiment 2 suggested that some of these errors were due to the
      influence of orthography.

PMID- 11961422
TI  - Using new information technology to treat tobacco dependence.
AB  - Smoking cessation programs that can be disseminated at a large scale and at a low
      cost are needed to decrease smoking-related mortality and morbidity. Research
      showed that several computer-based smoking cessation programs are effective, in
      particular when they are combined with pharmacotherapy. When available on the
      Internet, these programs can reach thousands of smokers at a low cost per
      participant. Some of these programs are designed to complement smoking cessation
      counseling given by physicians to their patients who smoke. They can be a useful
      adjunct to medical advice and should be prescribed in association with
      pharmacotherapy.

PMID- 11961423
TI  - Singing the chronic obstructive pulmonary disease blues.

PMID- 11961424
TI  - Are COPD patients with nocturnal REM sleep-related desaturations more prone to
      developing chronic respiratory failure requiring long-term oxygen therapy?
AB  - BACKGROUND: Nocturnal oxygen desaturations (NOD), especially during REM sleep,
      have been described in patients with COPD. However, the role of NOD in the
      evolution of COPD to chronic respiratory failure has not been well studied.
      OBJECTIVE: The aim of our study was to evaluate whether NOD is a risk factor for
      the development of chronic respiratory failure in COPD patients. METHODS: We
      studied 34 consecutive COPD patients with a stable daytime PaO(2) >60 mm Hg over
      a period of 42 months. We classified patients as desaturators (NOD) when episodic
      desaturations were found mainly during REM sleep, independently of baseline
      SaO(2) values. RESULTS: At enrollment 19 patients (55.8%) had NOD. Over the
      follow-up period, 10 patients (29.4%) were included in a long-term oxygen therapy
      (LTOT) programme (9 were desaturators). The LTOT was initiated a median time of
      22 +/- 6.8 months after enrollment. Patients who were subsequently prescribed
      LTOT had lower values of FEV(1) at enrollment, with a higher degree of NOD and
      PaCO(2). Stable respiratory failure developed earlier in patients with NOD: the
      two enrollment curves for LTOT differed significantly (log-rank test 2.56, p =
      0.005). PaCO(2), NOD and FEV(1) were statistically significantly associated, both
      in univariate and multivariate Cox proportional hazards analyses, with an
      increased risk of entering a LTOT programme. CONCLUSIONS: We conclude that NOD
      may represent an independent risk factor for the development of chronic
      respiratory failure in COPD patients with daytime PaO(2) >60 mm Hg. A larger
      study is needed to confirm the role of NOD in the natural history of COPD and
      subsequently to identify the most appropriate therapeutic approach.

PMID- 11961425
TI  - Effect of body position on arterial oxygen tension in the elderly.
AB  - BACKGROUND: It is well known that body position can have an effect on gas
      exchange though the magnitude of this effect has not been studied thoroughly in
      the elderly. OBJECTIVES: This study analyzes the effect body position change has
      on arterial oxygen tension (PaO(2)) and arterial carbon dioxide tension (PaCO(2))
      in healthy elderly. METHODS: We tested 46 "lung-healthy" elderly, including 30
      women and 16 men, 67-88 years of age. Blood was drawn from the radial artery
      first in the sitting position and subsequently in the supine position. Spirometry
      was performed. RESULTS: Mean (SD) sitting PaO(2) was 10.53 kPa (1.22), whereas
      mean supine PaO(2) was 9.85 kPa (1.33). The difference between sitting and supine
      PaO(2) was 0.68 kPa (0.86) and was statistically significant. Sitting PaCO(2) was
      5.06 kPa (0.47) and supine PaCO(2) was 5.05 kPa (0.54). The difference between
      sitting and supine PaO(2) correlated positively with FEV(1)/FVC %, negatively
      with the corresponding difference between sitting and supine PaCO(2), and
      negatively with BMI. CONCLUSIONS: We conclude that the significant difference in
      PaO(2) in sitting and supine positions clearly shows that the position needs to
      be considered both when attempting to establish reference values and when
      evaluating gas exchange in elderly persons. The positional changes in oxygenation
      are related to the corresponding change in PaCO(2), and to FEV(1)/FVC % and BMI.

PMID- 11961427
TI  - Rhinovirus is associated with severe asthma exacerbations and raised nasal
      interleukin-12.
AB  - BACKGROUND: Rhinovirus (RV) is associated with asthma exacerbations in
      longitudinal studies, but the role in patients with acute severe asthma who
      require admission to a hospital emergency room remains to be fully defined. The
      cytokines interleukin-10 (IL-10) and IL-12 may be elevated or suppressed by viral
      infections and contribute to a worsening of airway inflammation in asthmatics.
      OBJECTIVES: We assessed the association of RV with acute severe asthma and nasal
      IL-10 and IL-12. METHODS: Patients admitted to a hospital emergency asthma
      service had nasal aspirates (NAs) taken and peak expiratory flow (PEF) measured
      on admission and again 7, 28 and 56 days after admission. RV was sought in all
      NAs using a validated polymerase chain reaction assay and IL-10 and IL-12 were
      measured on admission and after 56 days in a subgroup of 22 asthmatics and 6
      normal controls. RESULTS: Thirty-seven asthmatics with a reduced PEF (%
      predicted) of 50.4 +/- 2.5% (mean +/- SEM) on admission were studied. RV was
      detected in NAs of 13 patients (35%) on admission, in 6 of the 13 patients after
      7 days (16%), in 1 patient after 28 and 56 days and was absent in controls. IL-10
      was not increased on admission or after 56 days. Measurements of IL-12 were
      raised on admission compared to 56 days later in asthmatics with RV detectable (p
      = 0.04). In asthmatics without RV, nasal IL-12 levels were correlated with PEF
      measurements over this period (r = 0.5, p < 0.05). CONCLUSIONS: A temporal
      relationship between the presence of nasal RV and emergency room admission for
      acute severe asthma was found in one third of patients. Low levels of IL-10
      during RV infections could contribute to unopposed synthesis of pro-inflammatory
      cytokines whilst increases in IL-12 may amplify nasal and endobronchial
      inflammation.

PMID- 11961426
TI  - Airway responsiveness to inhaled acetaldehyde in subjects with allergic rhinitis:
      relationship to methacholine responsiveness.
AB  - BACKGROUND: Asthmatic subjects have an exaggerated airway response to inhaled
      acetaldehyde, but no information is available on airway responsiveness to this
      bronchoconstrictor agent in subjects with allergic rhinitis. OBJECTIVE: The aim
      of this study was to determine the effect of inhaled acetaldehyde on lung
      function in nonasthmatic subjects with allergic rhinitis. METHODS: A total of 78
      adults (43 subjects with allergic rhinitis, 16 asthmatics and 19 healthy
      subjects) were challenged with increased concentrations of acetaldehyde and
      methacholine. The response to each bronchoconstrictor agent was measured by the
      provocative concentration required to produce a 20% fall in FEV(1) (PC(20)).
      RESULTS: The geometric mean PC(20) acetaldehyde value for asthmatics was 35.5
      mg/ml compared with 67.6 mg/ml in subjects with allergic rhinitis and with 80.0
      mg/ml in healthy subjects (p < 0.001). The PC(20) acetaldehyde values in the
      allergic rhinitis group were also significantly lower than in the healthy control
      group (p = 0.04). All of the subjects with allergic rhinitis and increased
      responsiveness to acetaldehyde showed airway hyperresponsiveness to methacholine,
      but 9 patients with hyperresponsiveness to methacholine failed to respond to
      acetaldehyde. CONCLUSIONS: We conclude that subjects with allergic rhinitis are
      less responsive to inhaled acetaldehyde than asthmatic subjects, but more than
      healthy controls. Furthermore, only approximately half the patients with allergic
      rhinitis and airway hyperresponsiveness to methacholine exhibit
      bronchoconstriction with inhaled acetaldehyde, thus suggesting that airway
      hyperresponsiveness to methacholine may not be the sole factor leading to
      bronchoconstriction in response to acetaldehyde.

PMID- 11961428
TI  - Increased lung uptake of technetium-99m hexamethylpropylene amine oxime in
      systemic lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) can affect every organ.
      Involvement of the lungs in this disease is a significant cause of morbidity and
      mortality. OBJECTIVES: To assess pulmonary vascular endothelium damage in SLE by
      lung uptake of technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO).
      METHODS: Lung uptake of (99m)Tc-HMPAO was measured in 20 SLE patients and for
      comparison in 25 controls without SLE, referred for brain imaging due to dementia
      or stroke. Of the 20 SLE patients, 10 had significant clinical pulmonary
      manifestations. However, all SLE patients had normal chest X-ray findings.
      Anterior lung image, including a large part of the liver, was taken 10 min after
      intravenous injection of 20-25 mCi of (99m)Tc-HMPAO. Regions of interest were
      calculated over the liver and lung. RESULTS: The mean lung/liver uptake ratio in
      patients without SLE was 0.36 +/- 0.1. The mean lung/liver uptake ratio in SLE
      patients was 0.79 +/- 0.58. The difference was significant. CONCLUSIONS: Our
      results indicated that determining the ratio of lung/liver uptake of (99m)Tc
      HMPAO may be a useful complementary method to assess pulmonary injury in SLE
      patients.

PMID- 11961429
TI  - Late-onset congenital cystic adenomatoid malformation of the lung. Embryology,
      clinical symptomatology, diagnostic procedures, therapeutic approach and clinical
      follow-up.
AB  - BACKGROUND: Congenital cystic adenomatoid malformation of the lung (CCAM) is an
      embryonic developmental anomaly of an unknown etiology usually diagnosed
      antenatally by imaging techniques. A minority of cases may not be identified by
      prenatal imaging techniques and may go unnoticed for the first 6 months of their
      extrauterine life. Due to its rarity, physicians are unlikely to suspect the
      condition. OBJECTIVES: To highlight the embryology, clinical symptomatology,
      diagnostic procedures, therapeutic approach and clinical follow-up of a series of
      12 patients with late-onset CCAM. METHODS: An observational study which offers
      the description of the clinical presentation, diagnostic methods, treatment and
      follow-up of 12 patients with late-onset CCAM. SETTING: A 600-bed teaching
      hospital in a reference area of 350,000 inhabitants. PATIENTS: 12 patients from
      1983 to 1999. RESULTS: Twelve diagnosed cases of late-onset CCAM. Mean age at
      diagnosis: 6.7 years (range: 6 months to 23 years). CLINICAL PRESENTATION: 9 out
      of 12 (75%) with repeated lung infections, 2 out of 12 (16%) chance finding, and
      1 case (8%) with pneumothorax. On pathological examination, 7 were found to be
      CCAM type I and 4 CCAM type II according to Stocker's classification; 1 patient
      is currently awaiting surgery. The diagnostic method of choice nowadays is a
      computed tomography (CT) scan performed in the 7 more recent cases; in the former
      5 cases an isotopic lung scan was done (and in 2 of them a bronchography was also
      performed). TREATMENT: 11 patients were operated: 8 lobectomies, 2
      segmentectomies and 1 localized resection. Mean follow-up: 8 years (range: 6
      months to 16 years). COMPLICATIONS: One reintervention due to a reappearance of
      the lesion in the patient who underwent localized resection of the CCAM. No cases
      of malignancy were found. CONCLUSIONS: Late-onset CCAM is an infrequent illness
      which requires a high level of clinical suspicion. It usually presents in the
      form of repeated infections. The most frequent pathological forms are type I and
      II (Stocker). The diagnostic method of choice is the CT scan. The recommended
      treatment is radical surgery of the lesion once diagnosis has been established.
      Malignancy and relapses are very infrequent when radical surgery is not
      postponed.

PMID- 11961430
TI  - Direct demonstration of the productive capability of cytokines at the single cell
      level in lung sarcoidosis using multicolor cytometry.
AB  - BACKGROUND: Sarcoidosis is a chronic systemic disorder of unknown etiology
      characterized by noncaseating epithelioid cell granulomatous lesions, around
      which an increasing number of CD4+ T cells infiltrate. These CD4+ T cells may
      release interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). These cytokines
      are considered to play an important role in pathogenesis of sarcoidosis. METHODS:
      We employed a modification of Jung's method using multicolor flow cytometry to
      assess the capability of single cells obtained from bronchoalveolar lavage (BAL)
      fluid to produce various cytokines. BAL CD4+ T cell production of IFN-gamma, IL-2
      and IL-4 after phorbol ester and ionomycin stimulation were studied. RESULTS: The
      percentage of IFN-gamma- and IL-2-producing CD4+ T cells was significantly higher
      in patients with sarcoidosis compared to healthy volunteers [84.7 +/- 7.5 vs.
      51.2 +/- 14.8% (p < 0.005), and 75.3 +/- 8.7 vs. 39.8 +/-11.0% (p < 0.001),
      respectively]. No significant difference in the percentage of IL-4-producing CD4+
      T cells was noted (1.2 +/- 0.6 vs. 3.5 +/- 2.6%; not significant), whereas the
      absolute number of IL-4-producing CD4+ T cells was significantly higher in
      patients with sarcoidosis compared to healthy volunteers (563.6 +/- 330.2 vs.
      50.9 +/- 66.9/ml; p < 0.005). In the IL-4-producing CD4+ T cells, about 80% of
      cells concomitantly produced IFN-gamma and more than 60% of cells also produced
      IL-2. CONCLUSION: We demonstrate that Th1-like-producing cells are predominant in
      the CD4+ as well as in the CD8+ T cell subset of patients with sarcoidosis. We
      for the first time demonstrated concomitant capabilities of BAL CD4+ T cells to
      produce Th1 and Th2 cytokines at the single cell level by multicolor flow
      cytometry.

PMID- 11961431
TI  - Leiomyosarcoma of the trachea masquerading as chronic asthma.

PMID- 11961432
TI  - A case of malignant pleural mesothelioma with unexpectedly long survival without
      active treatment.
AB  - Malignant pleural mesothelioma (MPM) is a disease with a very dismal prognosis. A
      median survival of 6-18 months is expected in most patients. Rarely, patients may
      survive unexpectedly long. We present the case of a patient with MPM who survived
      for more than 10 years without active treatment after the disease had been
      diagnosed.

PMID- 11961433
TI  - Intermittent positive airway pressure by nasal mask as a treatment for
      respiratory insufficiency in a patient with syringomyelia.
AB  - We report a case of a 73-year-old woman with chronic respiratory failure in
      association with syringohydromyelia and sleep apnea. She was initially intubated
      and mechanically ventilated. Weaning from the ventilator was only successful
      after nasal intermittent positive airway pressure therapy was started. A
      normalization of arterial blood gas exchange could be achieved.

PMID- 11961434
TI  - Disseminated Mycobacterium intracellulare infection in an HIV-negative,
      nonimmunosuppressed patient with multiple endobronchial polyps.
AB  - Endobronchial lesions caused by nontuberculous mycobacterial disease are
      extremely rare, but we recently encountered a case of disseminated disease due to
      Mycobacterium intracellulare presenting as multiple endobronchial polypoid
      lesions in an HIV-negative host. The patient was a 45-year-old Japanese female
      with fever, loss of body weight and cervical lymphadenopathy. Chest X-rays
      demonstrated a left hilar mass, and bronchoscopy revealed multiple polypoid
      lesions in the left main bronchus and bronchus of the left upper lobe. The
      infection later progressed, involving generalized lymphadenopathy, liver splenic
      and cutaneous abscesses, pulmonary infiltration, pleural effusion, and costal
      fracture. Finally, in two separate cutaneous abscesses M. intracellulare was
      identified by a DNA probe method. Antimycobacterial drugs were given, and the
      endobronchial lesions along with other symptoms and signs greatly improved.

PMID- 11961435
TI  - Multiple pulmonary arterial aneurysms in Behcet's disease: clinical and
      radiologic remission after cyclophosphamide and corticosteroid therapy.
AB  - Behcet's disease (BD) with pulmonary arterial aneurysm is rare and often
      associated with a poor prognosis. But there is also a chance that the aneurysm
      may completely resolve with medical therapy. A 39-year-old man presented with
      fever, malaise, bilateral chest pain, recurrent oral ulcers, and hemoptysis. The
      chest radiograph showed a round opacity in the right hilum. Computed tomography
      and magnetic resonance angiography (MRA) further revealed multiple, bilateral
      pulmonary arterial aneurysms consistent with the diagnosis of BD. The patient was
      started on a course of cyclophosphamide and corticosteroid therapy that resulted
      in cessation of his symptoms and complete resolution of radiologic findings. The
      chest radiograph and MRA reverted to normal on long-term follow-up. He is still
      alive and symptom-free 20 months after diagnosis.

PMID- 11961437
TI  - Extensive tracheobronchial wall thickening and luminal narrowing in a patient
      with longstanding hoarseness.

PMID- 11961436
TI  - Diffuse infiltrative lung disease associated with flecainide. Report of two
      cases.
AB  - We present two patients who developed subacute diffuse infiltrative lung disease
      while receiving flecainide for supraventricular arrhythmia. They had bilateral
      subpleural lung opacities on computed tomography. Bronchoalveolar lavage revealed
      increased numbers of lymphocytes and eosinophils, and a low CD4/CD8 ratio.
      Nonspecific interstitial pneumonia was documented by open lung biopsy in patient
      1. The outcome was favorable after flecainide withdrawal and prednisone
      treatment. Drug-induced pneumonitis should be suspected in patients treated with
      flecainide presenting with subacute diffuse infiltrative lung disease.

PMID- 11961438
TI  - Evidence-based medicine: a prescription to change the culture of pediatric
      orthopaedics.

PMID- 11961439
TI  - Juvenile-onset scoliosis followed up to adulthood: orthopaedic and functional
      outcomes.
AB  - This retrospective review describes 52 children with juvenile-onset scoliosis
      followed up for at least 2 years after skeletal maturity and completion of
      treatment. The purpose was to compare clinical and radiographic characteristics
      and curve progression, as well as orthopaedic, functional, and psychosocial
      outcomes in children treated by observation, bracing, or surgery. Seventeen
      percent of patients were treated with observation and 33% with bracing; and 50%
      required surgery. Median rib-vertebral angle difference and mean level of apical
      vertebra differed by treatment group. Neither brace nor surgical treatment
      negatively affected self-esteem. Results suggest that juvenile scoliosis is more
      likely to progress, less likely to respond to bracing, and more likely to require
      surgical treatment than adolescent idiopathic scoliosis.

PMID- 11961440
TI  - Radiographic outcomes using freeze-dried cancellous allograft bone for posterior
      spinal fusion in pediatric idiopathic scoliosis.
AB  - The senior author (A.G.) has gained extensive experience using freeze-dried
      cancellous allograft chips to obtain solid posterior fusion in patients with
      adolescent idiopathic scoliosis. The purpose of this study is to determine
      whether this form of allograft bone will yield successful fusion rates and
      maintain a minimal loss of curve correction when combined with current segmental
      posterior spinal instrumentation systems. Radiographs of 55 patients were
      evaluated by two masked reviewers using a previously devised grading system. At
      an average follow-up of 39 months (minimum 24 months), the overall fusion rate
      was 92.7% and the loss of curve correction was 3.4 degrees. The results of this
      study show that freeze-dried allograft chips yield successful fusion rates and
      only minimal loss of curve when combined with current posterior spinal
      instrumentation systems in patients with pediatric idiopathic scoliosis.

PMID- 11961441
TI  - Subcutaneous rodding for progressive spinal curvatures: early results.
AB  - This study retrospectively reviewed the clinical records and radiographs of 11
      patients with progressive early-onset scoliosis who failed to respond to
      nonoperative management and who underwent consecutive distraction of subcutaneous
      rods. Eleven children were treated by consecutive distraction of subcutaneous
      rods, and in two patients with rodding and anterior apical fusion. At surgery,
      the average patient age was 5.66 years, with a mean Cobb angle of 74 degrees and
      an average Pedriole angle of 39 degrees. The etiology of the scoliosis included
      four syndromic and one each congenital, post-rib resection, post-spinal tumor
      resection, neurofibromatosis, myelomeningocele, infantile idiopathic, and
      juvenile idiopathic. Subcutaneous rodding halted curve progression in all
      patients. At an average of 5.1 years after surgery, one patient showed no
      deterioration of the curve and nine patients showed an improvement of > or =40%
      in the magnitude of the original curvature. Eight of these patients had already
      had definitive surgery performed with segmental spinal instrumentation and
      fusion. Spinal growth occurred in all 11 patients and ranged from 0.5 to 4.5 cm
      (mean 2.0). Early results from these patients show that subcutaneous rodding with
      consecutive distraction allows correction of progressive early-onset scoliosis
      that failed to respond to nonsurgical management, preserving the individual
      growth potential of the spinal column and delaying definitive surgical treatment.
      Rotational deformity did not deteriorate radiographically, but clinical deformity
      increased subjectively. The amount of growth achieved and the number of
      procedures required to obtain these results raises the question of whether
      patients would be better served by a single anterior, posterior fusion and
      instrumentation at a young age.

PMID- 11961442
TI  - Posterior ISOLA segmental spinal system in the treatment of scoliosis.
AB  - The aim of the current study was to evaluate the effectiveness and safety profile
      of the posterior ISOLA Segmental Spinal System in the treatment of scoliosis.
      Forty-one patients (31 girls, 10 boys) were reviewed retrospectively. The average
      age was 14.2 years and the mean follow-up was 24 months. There were 32 cases of
      idiopathic scoliosis, 5 cases of neuromuscular scoliosis, and 4 miscellaneous
      types. An average of 12.3 levels were fused posteriorly. The average preoperative
      Cobb's angle, apical vertebral rotation, apical vertebral translation, lumbar
      lordosis, and thoracic kyphosis were 65.9 degrees, 2.2, 47.8 mm, 40 degrees, and
      28 degrees, respectively. The corresponding postoperative data were 34.4 degrees
      (47.8% correction), 1.8, 23.1 mm, 40.2 degrees, and 26.7 degrees. There were five
      minor complications and one deep wound infection. The ISOLA Segmental Spinal
      System was an effective and safe posterior system that could be used in different
      types and patterns of scoliosis with low complication rates.

PMID- 11961443
TI  - Surgical treatment of scoliosis in Marfan syndrome: guidelines for a successful
      outcome.
AB  - Twenty-three patients with Marfan syndrome who had a posterior spinal
      arthrodesis, with or without instrumentation, autogenous iliac crest bone graft,
      and postoperative immobilization were retrospectively reviewed to formulate
      guidelines for the treatment of scoliosis. Patients in group 1 (7 patients) had
      both the primary and secondary curves arthrodesed, whereas patients in group 2
      (16 patients) underwent selective arthrodesis of the entire primary and a partial
      arthrodesis of the secondary curves. Thirteen patients had triple curves, nine
      had double curves, and one patient had a single curve. At the time of follow-up
      all patients in group 1 had minimal or no progression of their curves, whereas 5
      patients in group 2 had minimal or no progression and 11 had marked progression
      of at least one curve. There were no pseudarthroses or hardware failures. The
      authors recommend arthrodesing both the primary and secondary curves in all
      patients with Marfan syndrome.

PMID- 11961444
TI  - Distinguishing scintigraphic features of spondylolysis.
AB  - A scintigraphic pattern of increased uptake was observed in the pedicles of the
      affected segment and a triangular pattern of uptake in the sagittal projection of
      tomographic studies of pars fractures. It was hypothesised that these
      observations were specific for pars fractures. A retrospective study of 25 young
      athletes (age 9-16 years) with a variety of spinal disorders was undertaken. Back
      pain was present for an average of 4 months. Diagnosis was confirmed by
      radiologic studies and/or response to treatment. All 15 children with
      spondylolysis had evidence of increased uptake in the ipsilateral or
      contralateral pedicle. None of the other causes of back pain showed this pattern.
      A specific triangular pattern of uptake was seen in the sagittal view in these
      patients. The authors describe two unique features of spondylolysis that add to
      the confidence with which the scintigraphic diagnosis may be made.

PMID- 11961445
TI  - Causes of false-negative ultrasound scans in the diagnosis of septic arthritis of
      the hip in children.
AB  - Ultrasound scans of the hip were carried out in 132 children with hip pain during
      an 18-month period to evaluate the hip for the presence of an effusion. Seventy
      three of these patients were followed up long enough to ascertain the presence or
      absence of septic arthritis. The remaining 59 patients were discharged with
      diagnoses other than septic arthritis but could not be located to confirm the
      ultimate accuracy of the diagnosis. Four patients were initially determined to
      have no effusion but subsequently were diagnosed with septic arthritis (false
      negative rate of 5%). Two of these patients had inadequate initial ultrasound
      examinations. Two children had ultrasound examinations that even on retrospective
      review did not reveal an effusion. Both of these children had had symptoms for
      <24 hours, and one had a contralateral hip effusion. The authors recommend using
      the negative results of an ultrasound scan as evidence of the absence of septic
      arthritis in children with caution when symptoms have been present for <24 hours
      or when bilateral disease exists.

PMID- 11961446
TI  - Short-term intravenous antibiotic treatment of acute hematogenous bone and joint
      infection in children: a prospective randomized trial.
AB  - Thirty-three cases of acute hematogenous bone or joint infection in children were
      randomly treated with short-term (7 days for joint infection, 10 days for bone
      infection) or long-term (14 days and 21 days, respectively) intravenous
      antibiotics after surgical drainage. The treatment outcome was measured through a
      detailed scoring system that included the ability to eradicate infection, the
      functional status of the limb, and the radiographic appearance of the bone and
      joint. The results were similar in both groups, showing the added benefit of a
      shorter hospital stay for children with blood-borne musculoskeletal infection.
      The use of this scoring system in choosing the route of antibiotic administration
      is recommended.

PMID- 11961447
TI  - Nontuberculous spondylodiscitis in children.
AB  - Forty-two children with nontuberculous spondylodiscitis treated between 1966 and
      1997 were reviewed, and the clinical, paraclinical, and therapeutic results are
      presented. The study shows the difficulties of diagnosis and understanding the
      pathophysiology of the disease. Additional information is provided by new imaging
      techniques, disc aspiration, and biopsy. The mean age at treatment was 4 years 6
      months. The initial clinical presentation was often misleading and the diagnosis
      was often delayed (42 days average). Standard radiographs and technetium bone
      scans were important for diagnosis and patient follow-up. Magnetic resonance
      imaging and needle aspiration of the disc gave an additional reliable aid in
      differential diagnosis and helped to guide treatment. Bacteria were isolated in
      22 of the 35 samples taken (55% Staphylococcus aureus, 27% Kingella kingae;
      Coxiella burnetii in one sample). The functional outcome is good if treatment is
      properly carried out. Disc fibrosis and occasional vertebral fusion develop
      inevitably in the long term. According to these results, nontuberculous
      spondylodiscitis is truly osteomyelitis of the spine.

PMID- 11961448
TI  - Deep vein thrombosis associated with pediatric musculoskeletal sepsis.
AB  - Deep vein thrombosis (DVT) is uncommon in children but can occur given certain
      circumstances. The authors describe four children in whom DVT developed in
      association with musculoskeletal sepsis. One child died. Prothrombotic screens
      were performed on the three surviving children, showing normal hematologic
      parameters. The severity of DVT complicating musculoskeletal sepsis is
      emphasized, particularly the potential for septic embolic complications. Deep
      vein thrombosis should be considered in any child with musculoskeletal sepsis,
      particularly when a limb is severely swollen or when there are pulmonary septic
      emboli.

PMID- 11961449
TI  - Primary subacute epiphyseal osteomyelitis: role of conservative treatment.
AB  - Primary subacute epiphyseal osteomyelitis is a rare disease. Owing to its
      insidious onset, mild symptoms, and inconsistent supportive laboratory data,
      diagnosis and treatment are usually delayed. The authors report a retrospective
      review of 16 patients with hematogenous osteomyelitis primarily affecting the
      epiphysis. In all of these patients an osteolytic lesion developed. In eight
      patients it was confined to the epiphysis or apophysis alone; in the other
      patients there was contiguous involvement of the adjacent metaphysis. Complete
      clinical and radiologic healing was observed in all patients after antibiotic
      therapy alone. Based on this experience, in view of the controversy in the
      literature, the authors recommend a conservative treatment policy in the
      management of both epiphyseal and epiphyseal-metaphyseal subacute osteomyelitis
      as the treatment of choice. Surgery should be reserved for persistent infection
      that does not respond to appropriate antibiotic therapy or when bone lesions
      cannot be distinguished from bone tumors by use of all available imaging
      modalities.

PMID- 11961450
TI  - Eight-year prospective targeted ultrasound screening program for instability and
      at-risk hip joints in developmental dysplasia of the hip.
AB  - The use of targeted ultrasound screening for at-risk hips to reduce the rate of
      surgery in developmental dysplasia of the hip is unproven. A prospective trial
      was undertaken in an attempt to clarify this matter. This study was undertaken
      between May 1992 and April 2000. There were 28,676 live births. Unstable and at
      risk hips were routinely targeted for ultrasound examination. One thousand eight
      hundred six infants underwent ultrasound examination (6.3% of the birth
      population). Twenty-five children (18 with dislocations, 7 with dysplasia)
      required surgical intervention in the form of open reduction of the hip or pelvic
      or femoral osteotomy (0.87 per 1,000 births for dysplasia, 0.63 per 1,000 births
      for dislocation). Targeted ultrasound screening does not reduce the overall rate
      of surgery compared with the best conventional clinical screening programs. The
      development of a national targeted ultrasound screening program for at-risk hips
      cannot be justified on a cost or result basis.

PMID- 11961451
TI  - Radiograph evaluation in children with acute hip pain.
AB  - Acute hip pain is relatively common in children. The etiology varies according to
      age and sex. Conventional radiography is commonly used to evaluate the painful
      hip. The views obtained depend on local departmental protocol, and there is no
      scientific basis for the choice of preferred projection. The authors' aim was to
      evaluate the role of anteroposterior (AP) and frog lateral (FL) radiographs in
      children younger than 14 years of age with hip pain to develop rational, evidence
      based investigation guidelines. Four investigators retrospectively reviewed AP
      and FL radiographs of 96 children. The results were analyzed using the chi-square
      statistic. Overall results showed a reduction in sensitivity to about 70% and
      specificity to 90% when using a single view instead of combined views. These
      results indicate that despite the potential risks of increased radiation exposure
      with more than one view, combined AP and FL radiographs improve the diagnostic
      accuracy compared with single views alone. The authors believe that the
      additional radiation burden is therefore justified.

PMID- 11961452
TI  - Prognostic value of Catterall and Herring classification in Legg-Calve-Perthes
      disease: follow-up to skeletal maturity of 32 patients.
AB  - To compare the prognostic value of the Catterall and Herring classification, 32
      patients, treated without surgery for unilateral Perthes diseases, were reviewed
      and classified at skeletal maturity according to Stulberg. The Catterall
      classification had no significant prognostic correlation with the final outcome.
      Only some head at-risk signs, such as lateral epiphyseal calcification and
      epiphyseal subluxation >4 mm, were prognostic. The Herring lateral pillar was not
      predictive when it was considered alone, but it became prognostic when related to
      age at onset. Moreover, in group C of the Herring classification (lateral pillar
      <50%), the final outcome was better in children younger than 6 years. This last
      observation strengthens the opinion that age and related residual skeletal
      moulding are also of prognostic value in Perthes disease.

PMID- 11961453
TI  - Adduction sign in pediatric hip arthrography.
AB  - Various techniques for improving the success of needle placement in hip
      arthrography have been described. The authors describe a simple consistent sign
      that occurs in both subluxated and dislocated hips and is present only when the
      needle is correctly placed within the hip joint. This, in conjunction with other
      techniques, has improved their quality of hip arthrography.

PMID- 11961454
TI  - Early reduction, arthrotomy, and cannulated screw fixation in unstable slipped
      capital femoral epiphysis treatment.
AB  - Sixteen consecutive cases of unstable slipped capital femoral epiphysis treated
      with urgent reduction and pinning during a 7-year period are presented. In 2 of
      the 16 patients, avascular necrosis of the femoral head developed. Ten of the 16
      patients were treated within 24 hours after the onset of acute symptoms by
      reduction, arthrotomy, and cannulated screw fixation of the hip using two screws.
      In none of these patients did avascular necrosis of the femoral head develop. Two
      patients required hardware removal for persistent pain, and one required a
      revision pinning after a nondisplaced femoral neck fracture. Chondrolysis did not
      develop in any patient, and no hip progressed after fixation. At last follow-up
      (mean 27 months after surgery), two patients walked with a moderate limp. Three
      reported persistent mild pain in the affected hip. Early reduction of unstable
      hips with arthrotomy and pinning using two cannulated screws to minimize the risk
      of avascular necrosis is recommended.

PMID- 11961455
TI  - Twenty-year follow-up of hip problems in arthrogryposis multiplex congenita.
AB  - Nineteen patients with arthrogryposis (38 hips) with significant hip problems
      were reviewed (13 dislocations, 9 subluxations, 16 contractures). The average
      follow-up was 20 years, with 15 patients reaching skeletal maturity. All patients
      had minimal or no pain. Thirteen of the 19 patients were community walkers. The
      dislocation group in general had more stiffness of the hip joint than the
      subluxation and the contracture groups. However, the long-term functional results
      were comparable among these three groups. Closed treatment always failed in
      treating dislocation of hips in arthrogryposis. Open reduction was successful in
      stabilizing the hip, but the hips were usually stiffer. However, after 20 years
      of follow-up, the function of the openly reduced hips was comparable with others.

PMID- 11961456
TI  - Upper extremity limb-length discrepancy in brachial plexus palsy.
AB  - Residual limb shortening is common after obstetric brachial plexus palsy. The
      exact limb-length discrepancy remains undetermined, and the purpose of this paper
      is to determine the resultant discrepancy. Twenty-two skeletally immature
      patients with obstetric brachial plexus palsies were examined. Radiographs of
      both the involved and uninvolved humerii and forearms were obtained with a
      radiographic ruler placed adjacent to the extremity. Each limb segment was
      measured and the discrepancy calculated as a percentage compared with the normal
      side. Twenty-one of the 22 children had some shortening of the limb at both the
      humerus and forearm level. The involved limb averaged 92% of the uninvolved limb.
      The humeral length averaged 93% and the forearm length averaged 90%. Children
      with upper brachial plexus lesions had significantly less forearm and total limb
      shortening compared with those with global lesions. There was no correlation
      between age and percentage difference of the humeral, forearm, and total length.

PMID- 11961457
TI  - Long-term results of lower limb lengthening by physeal distraction.
AB  - Of the many methods of limb elongation, lengthening by physeal distraction is
      among the newest. The goal of this study was to estimate the long-term results of
      femoral and tibial lengthening by epiphyseal distraction. The authors examined 40
      patients who underwent 24 femoral and 16 tibial lengthenings. The average follow
      up period was 9.6 years. An average of 4.6 cm of femoral lengthening and 4.7 cm
      of tibial lengthening was achieved. The femoral healing index was 38.1 days/cm
      and the tibial healing index was 35.7 days/cm. After lengthening the epiphyseal
      cartilage started to function in all patients, and premature growth cartilage
      fusion was not observed during follow-up. Complications occurred in eight
      patients during femoral lengthening and in four during tibial lengthening. The
      authors suggest that physeal distraction is a good method for moderate and simple
      limb lengthening. Particular care should be applied to knee joint function,
      especially during femoral lengthening.

PMID- 11961458
TI  - Long-term results of lower limb lengthening by the Wagner method.
AB  - Methods of limb lengthening have been continuously modified. The construction of
      an apparatus for gradual bone distraction was a great improvement. The aim of
      this study was to evaluate the long-term results of lower limb elongation using
      the Wagner technique. Between 1983 and 1989, 45 patients underwent surgery in the
      authors' institution. There were 31 femoral and 15 tibial lengthenings. The
      operation and lengthening procedure were performed according to the rules
      published by the method's author. The intended amount of lengthening was achieved
      in 80% of patients during tibial elongation and in only 52% during femoral
      elongation because of many problems, obstacles, and complications during
      treatment. A significant percentage of improper (deficient or irregular) new bone
      formation led to femoral malunion in three patients and to tibial and femoral
      delayed bone consolidation in six patients. Fast distraction produced great
      forces on the surrounding joint surfaces, resulting in a limited range of motion
      and joint stiffness. The Wagner technique does not seem to be effective and is
      associated with a long duration of treatment and some complications impairing the
      function of the limb.

PMID- 11961459
TI  - Early results of the modified Simmonds-Menelaus procedure for adolescent hallux
      valgus.
AB  - Adolescent hallux valgus is a common problem, and there is no agreement about the
      best surgical technique to use to correct this deformity. Excellent results have
      been reported with a distal soft tissue procedure and an associated osteotomy at
      the base of the first metatarsal. The current study reports the early results of
      using an incomplete osteotomy at the base of the first metatarsal. No hardware
      was used to fix the osteotomy, and the postoperative immobilization was shorter.
      The study included 20 feet in 11 female patients. All osteotomies healed
      primarily without complications. The average preoperative hallux valgus of 31.2
      degrees was reduced to 17.8 degrees at a minimum of 2 years follow-up. The
      average intermetatarsal angle improved from 13.5 degrees in the preoperative
      period to 11.3 degrees. Using the duPont bunion rating score as an outcome
      assessment, the authors had 4 excellent and 16 good results.

PMID- 11961460
TI  - Pediatric unilateral below-elbow amputees: retrospective analysis of 34 patients
      given multiple prosthetic options.
AB  - Thirty-four unilateral below-elbow amputees from the Shriners Hospitals for
      Children/Twin Cities were retrospectively analyzed in long-term follow-up. All of
      these patients were provided with a variety of prosthetic options, including a
      "passive" cosmetic upper extremity device. Most of the patients were also fitted
      with conventional prostheses using a body-powered voluntary closing terminal
      device (97%) as well as myoelectric prostheses (82%). These patients were
      considered consistent prosthetic users by the clinic team. The average follow-up
      was 14 years, with many of the patients being followed up throughout their entire
      childhood. All patients were sent questionnaires, and the authors carried out
      patient interviews and chart review. Final analysis indicated that 15 patients
      (44%) selected a simple cosmetic "passive hand" as their prosthesis of choice. In
      long-term follow-up 14 patients (41%) continued as multiple users. Fourteen
      patients (41%) selected the conventional prosthesis using a voluntary closing
      terminal device as the prosthesis of choice. Only five patients (15%) selected
      the myoelectric device as their primary prosthesis. The authors conclude that
      successful unilateral pediatric amputees may choose multiple prostheses on the
      basis of function and that frequently the most functional prosthesis selected in
      the long term is the simplest in design. The authors believe strongly that
      unilateral pediatric amputees should be offered a variety of prosthetic options
      to help with normal activities of daily living.

PMID- 11961461
TI  - Surgical prevention of foot deformity in patients with Duchenne muscular
      dystrophy.
AB  - The purpose of this study was to evaluate the results of a modification of the
      posterior tibial tendon transfer in Duchenne muscular dystrophy patients with
      regard to foot deformity and ambulation. The records of 57 patients with Duchenne
      muscular dystrophy were retrospectively reviewed. Three treatment groups were
      studied: group 1, those who had surgery to maintain ambulation; group 2, those
      who had surgery to correct and maintain foot position; and group 3, those who had
      no surgery. All surgical patients had posterior tibial tendon transfer and
      Achilles tendon lengthening as part of their procedure. Thirty-four patients
      returned for interviews and examinations to assess outcomes and foot position.
      The mean age at cessation of ambulation for those who had surgery was 11.2 years
      versus 10.3 years for those who did not have surgery. Of 48 feet in 24 patients
      who underwent lower extremity surgery to correct and maintain foot position, 94%
      were clinically satisfactory at a mean of 8.5 years after surgery. Regardless of
      the desire to continue ambulation, all patients should have posterior tibial
      tendon transfer, Achilles tendon lengthening, and toe flexor tenotomies to
      maintain plantigrade feet.

PMID- 11961462
TI  - Pediatric lower extremity surgery using a hand table.
AB  - Operating on the pediatric lower extremity has its own inherent challenges due to
      the diversity of the problems, the smaller size of the patient, and the often
      distorted anatomy associated with congenital malformations. Additional concerns
      arise with respect to positioning on the operating table to meet the surgeon's
      comfort, the anesthesiologist's need for proximity, and facility of radiographic
      imaging. The authors use a standard hand table to ameliorate these additional
      concerns without allocation of additional hospital resources.

PMID- 11961463
TI  - Late open reduction internal fixation of lateral condyle fractures.
AB  - To study the effects of late open reduction of lateral condyle fracture (LCF) on
      avascular necrosis (AVN), amount of displacement, and improvement, the records of
      11 children with an open capitellar physis and a malunion or a nonunion treated
      >3 weeks after injury were reviewed. Preoperative and postoperative displacement
      amounts were recorded. Radiographs were reviewed for AVN, lateral overgrowth, or
      fishtail deformity. There were no cases of AVN. Three patients had occasional
      pain. Four patients had displacement of >10 mm before surgery. In fractures with
      >1 cm of displacement, fragment position was minimally improved surgically, but
      final alignment and range of motion were good. These fractures showed more
      radiographic deformities at the time of late open reduction. The risk of AVN with
      late open reduction of LCF at >3 weeks is reduced if no tissue is stripped off
      the fracture fragment posteriorly. Even children without anatomic reduction had
      functional arms with little or no pain.

PMID- 11961464
TI  - Orthopaedic manifestations of Marinesco-Sjogren syndrome.
AB  - Two patients with Marinesco-Sjogren syndrome had striking orthopaedic
      abnormalities that seemed to arise from multiple areas of physeal growth arrest.
      Major involvement was seen in the distal femora, where bilateral hypoplasia of
      the lateral condyles resulted in progressive valgus, patellar dislocation, and
      quadriceps dysfunction. Marinesco-Sjogren syndrome seems to arise from an error
      in lysosomal handling of lipids. Timely orthopaedic intervention may be helpful
      in prolonging ambulation in these patients.

PMID- 11961465
TI  - Prenatal ultrasonography in antenatal orthopaedics: a new subspecialty.

PMID- 11961466
TI  - Early failure of Pavlik harness treatment of developmental hip dysplasia:
      clinical and ultrasound predictors.

PMID- 11961467
TI  - The use of allografts for Pemberton osteotomies.

PMID- 11961470
TI  - Comparing health care systems: the importance and limitations of outcome
      measures.

PMID- 11961468
TI  - The effect of early amniocentesis on foot deformity in the neonate.

PMID- 11961472
TI  - Personal choices of health plans by managed care experts.
AB  - BACKGROUND: Expert opinion has not been used as a basis for comparing different
      forms of health insurance, in part because this perspective may not be
      appropriately sensitive to aspects of care that consumers value. RESEARCH DESIGN:
      Using a case-control design, managed care experts were surveyed at 17 academic
      institutions in the United States to determine the type of health plan they chose
      (fee-for-service, HMO, POS, PPO, or catastrophic). Controls consisted of
      academicians from other disciplines at these institutions who ostensibly faced
      the same insurance options. We then compared the choices of physician experts,
      nonphysician experts and controls using a multinomial logit model that was
      sensitive to the choice set available at each institution. We also examined the
      choice behavior of respondents within moderate (< $150,000) and high (> or
      =$150,000) income levels. RESULTS: Four hundred thirty-seven experts and 465
      controls were surveyed and responses were received from 73.7% and 52.7%,
      respectively. Physician experts were approximately half as likely (14.9%) as
      controls (26.6%) or nonphysician experts (27.6%) to enroll in HMO plans. In
      moderate-income households, both physicians (Relative Risk [RR] = 0.42; P <0.01)
      and nonphysician experts (RR = 0.71; P <0.1) were less likely than controls to
      opt for an HMO. Experts' propensity to choose HMO coverage varied little with
      income, whereas controls' propensity changed dramatically between moderate (39.1%
      in HMOs) and high (14.0% in HMOs) income categories. CONCLUSIONS: The aversion of
      physician experts, and nonphysician experts with moderate income, to HMO plans
      may be caused by their stronger distaste for the constraints on choice and access
      that typically accompany HMO coverage. Alternatively, it may be explained by
      their superior ability to absorb, understand, and use information about available
      insurance options. Insights into quality in managed care may also play a role.

PMID- 11961471
TI  - Health care factors related to stage at diagnosis and survival among Medicare
      patients with colorectal cancer.
AB  - BACKGROUND: With the growth in enrollment of Medicare patients in HMOs the
      effectiveness of care received by Medicare/HMO patients continues to be of
      concern. By considering the relationship of insurance to stage at diagnosis, this
      study inquires whether HMOs emphasize early diagnosis of colorectal cancer to a
      greater extent than FFS plans, if particular HMO types (group/nongroup models)
      are more successful in doing so, and how this pertains to survival. METHODS: Data
      for 1329 Medicare patients with colorectal cancer, diagnosed 1987 to 1993, and
      residing in northern California, were acquired from a population-based cancer
      registry. Insurance included two types of Medicare HMOs (group and nongroup
      model) and three fee-for-service (FFS) categories: Medicare with private
      supplement, Medicare/Medicaid, and Medicare only. The relationships of insurance
      to AJCC stage at diagnosis and of insurance to survival following diagnosis were
      examined, respectively, with logistic regression models and survival analysis
      (controlling for age, ethnicity, tumor location, educational level, sex, and
      hospital type). RESULTS: Likelihood of early stage colorectal cancer was greater
      for Medicare patients in nongroup model HMOs or having private FFS supplements
      than for those in group model HMOs, Medicare/Medicaid, or Medicare alone. All
      cause and colorectal cancer mortality did not differ significantly among Medicare
      patients with group model HMO, nongroup model HMO and private FFS supplements.
      Medicare/Medicaid patients experienced significantly greater all-cause mortality
      than private FFS patients. CONCLUSIONS: Differences within this study population
      in early stage diagnosis of colorectal cancer and breast cancer, respectively, by
      type of Medicare supplemental insurance may be attributable to which preventive
      screening measures are included in health plan report cards.

PMID- 11961473
TI  - Searching literature databases for health care economic evaluations: how
      systematic can we afford to be?
AB  - BACKGROUND: As the health care economic-evaluation literature continues to grow,
      a need for sound methods to conduct systematic reviews of the existing evidence
      is emerging. So far, reviews of economic evaluations have relied upon
      noncomprehensive sources and have adopted simplistic search methods, both likely
      to lead to biased results. OBJECTIVE: To provide evidence of the performance of
      alternative approaches for identifying published health care economic evaluations
      and to illustrate what forms of bias may affect systematic reviews of such
      studies. METHODS: The sensitivity and specificity of alternative search
      strategies were tested for the period January to March 1997, using seven major
      medical and social science literature databases, one economic evaluation database
      and a published bibliography. Studies were selected blindly by pairs of reviewers
      (agreement 94.1%-96.5%), using a two-stage procedure. RESULTS: By limiting the
      scope of a review to Medline and by using appropriate search strategies,
      researchers may significantly reduce the number of nonrelevant references
      retrieved by their electronic searches (sensitivity 72%, specificity 75%,
      compared with more extensive strategies), which require exclusion by manual
      screening. The yield of searches based on specialized bibliographies and
      databases may be different because of variations in selection criteria, coverage
      and time lag for inclusion of references. CONCLUSIONS: Medline is the key source
      for reviews of economic evaluations. Researchers may select from the search
      strategies proposed in this paper the one that offers an optimal balance between
      sensitivity and specificity in relation to the aims of their review. Manual
      searches and searches of databases other than Medline have a limited incremental
      yield. The sensitivity of all search strategies increases when tighter
      methodological standards are set, but more research is needed on methods for
      identifying methodologically sound studies.

PMID- 11961474
TI  - Health literacy and preventive health care use among Medicare enrollees in a
      managed care organization.
AB  - BACKGROUND: Many older adults in Medicare managed care programs have low health
      literacy, and this may affect use of preventive services. OBJECTIVES: To
      determine whether older adults with inadequate health literacy were less likely
      to report receiving influenza and pneumococcal vaccinations, mammograms, and
      Papanicolaou smears than individuals with adequate health literacy after
      adjusting for other covariates. RESEARCH DESIGN: Cross-sectional survey; home
      interviews with community dwelling enrollees. SUBJECTS: Medicare managed care
      enrollees 65 to 79 years old in four US cities (n = 2722). MEASURES: Short Test
      of Functional Health Literacy in Adults and self-reported preventive service use.
      RESULTS: In bivariate analyses, self-reported lack of preventive services was
      higher among individuals with inadequate health literacy than those with adequate
      health literacy: never had an influenza vaccination: 29% versus 19% (P = 0.000);
      never had a pneumococcal vaccination: 65% versus 54% (P = 0.000); no mammogram in
      the last 2 years: 24% versus 17% (P = 0.017); never had a Papanicolaou smear: 10%
      versus 5% (P = 0.002). After adjusting for demographics, years of school
      completed, income, number of physician visits, and health status, people with
      inadequate health literacy were more likely to report they had never received the
      influenza (OR, 1.4; 95% CI, 1.1-1.9) or pneumococcal vaccination (OR, 1.3; 95%
      CI, 1.1-1.7), and women were less likely to have received a mammogram (OR, 1.5;
      95% CI, 1.0-2.2) or Papanicolaou smear (OR, 1.7; 95% CI, 1.0-3.1). CONCLUSIONS:
      Among Medicare managed care enrollees, inadequate health literacy is
      independently associated with lower use of preventive health services.

PMID- 11961475
TI  - Why are hospital-based nursing homes so costly? Relative importance of acuity and
      treatment setting.
AB  - OBJECTIVES: To determine the extent to which higher costs in hospital-based
      skilled nursing facilities (HBSNF) can be explained by observable resident
      characteristics and unobservable selection effects, implying a design shortcoming
      of the skilled nursing facility prospective payment system (SNF PPS) implemented
      for Medicare-covered stays by the Balanced Budget Act of 1997 (BBA 1997).
      RESEARCH DESIGN: Data on resident characteristics from the Minimum Data Set (MDS)
      are combined with staff time costs from the Centers for Medicare and Medicaid
      Services' (CMS, formerly HCFA) 1995 and 1997 SNF Staff Time Measurement (STM)
      studies and nontherapy ancillary claim costs extracted from CMS SNF claim
      records. An endogenous switching model was estimated to measure the effect on
      costs of the relatively high acuity of HBSNF residents, net of differences purely
      attributable to the treatment setting. RESULTS: It was found that virtually the
      entire HBSNF differential is attributable to setting effects with resident
      characteristics and selection effects playing a negligible role. In addition, it
      was found that marginal costs associated with particular services and conditions
      are often lower in hospital-based than in freestanding facilities. CONCLUSIONS:
      HBSNFs incur high costs regardless of the characteristics of their residents.
      Their high fixed costs accompany relatively low marginal costs associated with
      admitting high-acuity residents. Consequently, a PPS casemix system that depends
      on resident characteristics and excludes consideration of facility
      characteristics (as mandated by BBA 1997) need not unfairly penalize HBSNFs,
      provided a powerful casemix system is used and HBSNFs specialize in the care of
      high-acuity residents.

PMID- 11961476
TI  - Organizational interventions to improve health outcomes of older persons.
AB  - BACKGROUND: With the reorganization of the financing of health care and creation
      of systems of care, it is possible to design and implement organizational
      interventions to improve the care of older persons beyond the services that can
      be provided by an individual provider. OBJECTIVES: To review the effectiveness of
      organizational interventions for older persons, describe barriers to
      dissemination of success models into practice settings, and identify future
      directions for such interventions. METHODS: Selective review of organizational
      interventions that have been aimed primarily at the geriatric population and have
      been formally evaluated using conventional research designs, usually randomized
      clinical trials. RESULTS: Organizational interventions can be classified into two
      groups: component models and systems changes. The former can be superimposed upon
      an intact system but do not fundamentally change the system of care whereas the
      latter modify the basic structure of primary care. A variety of organizational
      interventions have been implemented in diverse settings, but the evidence
      supporting the effectiveness of these interventions is inconsistent. Even when
      such interventions have been effective in research settings, these interventions
      rarely reduce health care costs. Moreover, there have been formidable barriers to
      implementation of successful interventions into practice. CONCLUSIONS:
      Organizational interventions are potentially powerful methods to influence health
      care and maintain health status of older persons. Nevertheless, gaps between
      knowledge and practice and unanswered questions about the effectiveness of
      organizational interventions currently limit the potential value of this approach
      to improving health care of older persons.

PMID- 11961477
TI  - State AIDS Drug Assistance Programs: equity and efficiency in an era of rapidly
      changing treatment standards.
AB  - BACKGROUND: The 54 state AIDS Drug Assistance Programs (ADAP) provide medications
      to HIV-infected persons with limited resources. Eligibility and coverage vary,
      raising concerns about health inequities. OBJECTIVE: To compare the relative
      clinical and economic performance of ADAP programs. RESEARCH DESIGN: A state
      transition simulation model of HIV disease was used to explore the clinical
      consequences and lifetime costs associated with selected state policies. Clinical
      data came from the Multicenter AIDS Cohort Study, AIDS Clinical Trials Group
      Protocol 320, and other published randomized trials. Cost data came from the
      national AIDS Cost and Services Utilization Survey, and the 1999 Red Book. ADAP
      data came from National Association of State and Territorial AIDS Directors
      reports and interviews. MEASURES: Projected life expectancy, quality-adjusted
      life expectancy, total lifetime direct medical costs, cost-effectiveness in
      dollars per quality-adjusted life year (QALY) gained. RESULTS: ADAPs vary
      considerably in terms of formulary policies, health outcomes, expected costs, and
      cost-efficiency. Conservative projections, based on a cohort with starting mean
      CD4 count of 250 cells/microL, yield life expectancies ranging from 5.36 to 6.81
      life years (4.69-6.01 quality-adjusted life years [QALYs]). Total per person
      lifetime direct medical costs range from $81,200 to $112,700; higher costs
      reflect increased spending on medications. Expected costs per QALY gained range
      from $7000 to $28,000. Under pessimistic assumptions regarding initial CD4
      counts, drug efficacy, and discounting, the most comprehensive policy remains
      below $33,000/QALY. CONCLUSIONS: Even the most comprehensive ADAPs constitute a
      cost-effective use of HIV care resources. A uniform, national ADAP formulary
      warrants consideration.

PMID- 11961478
TI  - Modelling valuations for Eq-5d health states: an alternative model using
      differences in valuations.
AB  - OBJECTIVES: The EQ-5D is a preference-based measure of health and is increasingly
      being used in the evaluation of health technologies. A 'tariff' of values for all
      243 EQ-5D health states has been generated using direct valuations on a subset of
      these states. The tariff is used to express the value of differences between
      health states, and so this paper explores whether a tariff with better predictive
      ability can be calculated using differences between values rather than using the
      values themselves. METHODS: The original tariff (reported in this journal) was
      based on valuations for 42 EQ-5D states elicited from a representative sample of
      2997 members of the UK general population using the time trade-off method. This
      same data are used to estimate a tariff based upon the differences in value
      between the worst possible state (33333) and all other states. RESULTS: A simple
      model that fits the data well is one in which the differences in value between
      33333 and all other states are explained in terms of the change in each dimension
      plus a term to pick up whether some dimensions change by the maximum amount
      whereas others do not change at all. The mean absolute difference between the
      actual values and those predicted by this model is 0.03 (compared with 0.039 in
      the original model). CONCLUSION: The model presented in this paper predicts the
      difference between 33333 and all other states remarkably well and can be used to
      generate a tariff for all EQ-5D health states. In fact, this model more
      accurately predicts the values of states for which there are direct observations,
      and so we recommend its comparison with the original model in evaluative studies.

PMID- 11961479
TI  - A guest editorial: what is the correct cesarean rate and how do we get there?

PMID- 11961480
TI  - Insulinoma in pregnancy: a case report and review of the literature.
AB  - Insulinomas are rare tumors with an incidence of approximately four cases per
      million person-years. Nineteen cases of insulinoma during pregnancy have been
      reported. Hypoglycemic symptoms usually appear during the first trimester. A 28
      year-old primigravida was admitted at 6 weeks of gestation after referral for
      uncontrolled seizures. Her previous seizure work-up included a normal EEG and a
      normal magnetic resonance imaging of the brain. Elevated fasting insulin and C
      peptide levels accompanied severe hypoglycemia. The patient was managed with
      glucose monitoring, frequent small meals, and rare doses of glucagon. Postpartum
      testing was consistent with insulinoma, and magnetic resonance imaging indicated
      a mass in the tail of the pancreas. During surgical exploration with
      intraoperative ultrasound, two insulinomas were removed from the tail of the
      pancreas. The hypoglycemic episodes resolved and the fasting glucose levels
      normalized. Insulinomas are rare in pregnancy and can be difficult to diagnose.
      Symptoms may resolve during the second and third trimesters, possibly due to
      changes in glucose metabolism associated with pregnancy. Misdiagnosis has been
      fatal. Careful management during pregnancy and aggressive treatment after
      delivery are essential. TARGET AUDIENCE: Obstetricians and Gynecologists, Family
      Physicians. LEARNING OBJECTIVES: After completion of this article, the reader
      will be able to describe the pathophysiology of an insulinoma, to list the
      potential tests used to make the diagnosis of insulinoma, and to outline
      potential treatment options for a patient with an insulinoma.

PMID- 11961481
TI  - Nonbilharzial bladder carcinoma complicating pregnancy: review of the literature.
AB  - The purpose of this review is to evaluate tumor presentation and characteristics,
      and maternal-fetal outcomes of pregnancies complicated by nonbilharzial bladder
      carcinoma. The mean age of the patients was 29.5 years (range = 18-40). Symptoms
      and diagnosis occurred after the first trimester in 20 (83%) and 22 (92%) cases,
      respectively. Presenting complaints included painless gross hematuria [N = 12
      (50%)], vaginal bleeding [N = 7 (29%)], dysuria [N = 2 (8.4%)], abdominal pain [N
      = 2 (8.4%)], and 1 instance each of urgency, frequency, recurrent cystitis, and
      no symptoms. Tumors were initially identified by ultrasound [N = 12 (50%)],
      cystoscopy [N = 11 (46%)], and intravenous urography [N = 1 (4.5%)]. Transitional
      cell carcinoma was found in 17 (74%), adenocarcinoma in 5 (22%), and squamous
      cell carcinoma in 1 (4.5%) patient. Tumors did not favor a specific bladder
      location, tended to be low grade [8 (40%) = grade 1, 7 (35%) = grade 2; 5 (21%) =
      grade 3], and noninvasive [N = 19 (79%)]. Treatment was typically by
      transurethral resection (N = 18), but 3 women required radical cystectomy, 2
      received radiation, 1 received chemotherapy, and 1 underwent partial cystectomy.
      Three (14%) women died of their disease and 3 (14%) fetuses were lost because of
      complications of cancer or its treatment. Bladder carcinoma in pregnancy can
      mimic cystitis or obstetric hemorrhage and should be considered when evaluations
      for these conditions are negative. Routine ultrasound evaluation of the bladder
      in these patients may improve the diagnostic yield. Pregnancy is not a
      contraindication to treating most forms of bladder cancer. TARGET AUDIENCE:
      Obstetricians and Gynecologists, Family Physicians. LEARNING OBJECTIVES: After
      completion of this article, the reader will be able to list the various types of
      bladder cancers, to describe the presenting symptoms in a patient with a bladder
      cancer, and to outline the work up and treatment strategies for bladder cancer.

PMID- 11961482
TI  - Congenital cytomegalovirus infection: review of the epidemiology and outcome.
AB  - Cytomegalovirus (CMV) is one of the most common viral causes of congenital
      infection. A future decision to lower its incidence by vaccination will depend on
      epidemiological conditions within a country and on the safety of the vaccine to
      be used, because a life vaccine may cause latency and subsequent reactivation
      that still may harm the fetus. The aim was to review the epidemiological studies
      published so far, with respect to factors that affect the incidence of congenital
      CMV infection, and factors that may influence its outcome, such as preexisting
      maternal immunity. The study included the data of 19 studies that were retrieved
      from a MEDLINE search during the period 1977 to 1997. The incidence of congenital
      CMV infection varied between 0.15% and 2.0% and seemed to correlate with the
      level of preexisting immunity in the population. Although preexisting maternal
      immunity was reported to strongly reduce transmission, the severity of congenital
      CMV infection (symptoms at birth and or sequelae later in life) was not
      significantly greater after virus transmission due to a primary infection of the
      mother as compared with recurrence or reinfection. The data indicate that
      preexisting immunity of the mother does not significantly mitigate the outcome of
      congenital infection. Moreover, life vaccines may bear a serious risk when
      transmittable to the fetus. TARGET AUDIENCE: Obstetricians and Gynecologists,
      Family Physicians. LEARNING OBJECTIVES: After completion of this article, the
      reader will be able to describe the natural course of a CMV infection, to list
      the potential sequelae of a congenital CMV infection, to outline potential
      strategies to prevent transmission of CMV, and to summarize the diagnostic work
      up of a patient with a potential CMV infection.

PMID- 11961483
TI  - Enzyme leakage, trypsinogen activation, and inflammatory response in endoscopic
      retrograde cholangiopancreatography-induced pancreatitis.
AB  - INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP)-induced
      pancreatitis (EIP) provides an opportunity to study different pathophysiologic
      events early in the course of acute pancreatitis. AIMS: To investigate whether
      the leakage of pancreatic proenzymes (anionic trypsinogen), pancreatic protease
      activation (carboxypeptidase B activation peptide), cytokine response
      (interleukin [IL]-1 receptor antagonist, IL-6, and soluble tumor necrosis factor
      receptor-I) and neutrophil activation (neutrophil gelatinase-associated lipocalin
      and polymorphonuclear elastase) differ between patients with and without EIP. A
      second aim was to clarify the temporal relation between these different events.
      METHODOLOGY: Ninety-nine nonconsecutive patients undergoing ERCP were
      investigated in the study. RESULTS: Fourteen of 99 patients undergoing ERCP
      developed mild EIP. Six hours after the investigation the concentration of
      anionic trypsinogen was significantly higher in patients with EIP than in
      patients without EIP. The day after ERCP, higher concentrations of anionic
      trypsinogen, carboxypeptidase B activation peptide, IL-6, and polymorphonuclear
      elastase were recorded in the EIP group. No significant differences in IL-1
      receptor antagonist, soluble tumor necrosis factor receptor-I or neutrophil
      gelatinase-associated lipocalin were found between the groups in this study.
      CONCLUSION: Mild EIP was accompanied by early leakage of proenzymes and later
      activation of trypsinogen/proteases. A significant cytokine response and
      neutrophil activation were recorded the day after ERCP, but further studies are
      needed to determine the temporal relation between these different
      pathophysiologic events.

PMID- 11961484
TI  - Use of biocytin as neuroanatomic tracer in harvested human pancreas: a confocal
      laser scanning microscopy analysis.
AB  - INTRODUCTION: To identify central neuroanatomic structure, biocytin labeling has
      recently been used. To date, there are no bibliographic references about the use
      of this molecule in investigations of the peripheral nervous system. In the
      present study, fresh, harvested human pancreas was used to evidence pancreatic
      innervations by biocytin. AIM: To investigate for the first time pancreatic
      innervation in harvested pancreas from human multiorgan cadaveric donors.
      METHODOLOGY: Biocytin labeling was used as a neuroanatomic tracing method, and
      confocal laser scanning microscopy was used for analysis for description by means
      of high-resolution images. RESULTS: The application of biocytin-avidin staining
      in harvested human pancreas revealed numerous bundles of nervous fibers,
      intrapancreatic ganglia, few small solitary neurons, and a large number of
      positive supporting cells (glial-like cells). Biocytin appeared to pass through
      gap junctions between glial elements and neurons and among the neurons. In human
      pancreas, biocytin is rapidly transported in both anterograde and retrograde
      directions, with consequent visualization of fine details of pancreatic
      innervation morphology. Indeed, evidence of anterograde and retrograde
      transportation of biocytin has been demonstrated in the extensive labeling of
      pancreatic preganglionic and postganglionic fibers as well as a great number of
      chemical buds that wind through exocrine tissue or undetermined target cells.
      CONCLUSION: To our knowledge, this is the first report of the successful use of
      biocytin in neuronal retrograde and anterograde labeling in the human peripheral
      nervous system.

PMID- 11961485
TI  - Processing of the major pancreatic zymogen granule membrane protein, GP2.
AB  - INTRODUCTION: The pancreatic exocrine secretory granule, the zymogen granule,
      releases digestive enzymes into the intestine. GP2 is the most abundant zymogen
      granule membrane protein. Coincident with exocrine secretion, GP2 is released
      from the membrane and secreted into the pancreatic duct. AIM: To characterize
      changes in the structure of GP2 as it progresses through the secretory pathway.
      METHODOLOGY: Polarized MDCK cells that express the rat GP2 gene were used to
      examine the sequential processing of the polypeptide backbone. RESULTS: Within
      the cell, GP2 is initially proteolytically processed from a 55- to a 53-kd form
      at or before the trans-Golgi network. The protein is then processed to a 51-kd
      form, which is found on the apical plasma membrane and in secretions. Similar
      processing was also observed in primary rat pancreatic cultures and in MDCK cells
      that express human GP2. The amino-terminal sequence of human GP2 derived from
      pancreatic secretions was determined for two human patients and began at Gly39,
      revealing a potential processing site. CONCLUSIONS: In contrast to other
      digestive enzymes secreted by the pancreas that are activated by proteolysis in
      the intestine, GP2 undergoes sequential intracellular cleavage. Alterations in
      GP2 structure by proteolysis may regulate GP2 function at specific sites within
      the pancreatic cell.

PMID- 11961486
TI  - Matrix metalloproteinase-2 in pancreatic juice for diagnosis of pancreatic
      cancer.
AB  - INTRODUCTION: Matrix metalloproteinase-2 (MMP-2) has an activity to degrade type
      IV collagen and is associated with invasion angiogenesis of malignant tumor. AIM:
      A diagnostic value of MMP-2 in pancreatic juice was studied in the diagnosis of
      pancreatic cancer. METHODOLOGY: Using gelatin zymography, active MMP-2 and proMMP
      2 were determined in pancreatic juice obtained endoscopically from 12 patients
      with pancreatic cancer, 11 with chronic pancreatitis, and 7 control subjects.
      RESULTS: ProMMP-2 was detected in 12 of 12 patients (100%) with pancreatic
      cancer, 6 of 11 (54.5%) with chronic pancreatitis, and 3 of 7 (42.9%) controls.
      Active MMP-2 was detected in 11 patients (91.6%) with pancreatic cancer, 2
      (18.2%) with chronic pancreatitis, and none of the control subjects. An
      activation ratio of MMP-2 (active MMP-2/total MMP-2) in pancreatic juice is
      significantly higher in pancreatic cancer (23.4 +/- 4.4%, mean +/- SE) than in
      chronic pancreatitis (2.1 +/- 1.7%) and controls (0%) (p < 0.01). Active MMP-2
      was also detected in pancreatic juice from three cases of small pancreatic cancer
      (tumor <2 cm in diameter). CONCLUSION: Our observation suggests that detection of
      active MMP-2 in pancreatic juice using gelatin zymography may be useful for the
      diagnosis of pancreatic cancer.

PMID- 11961487
TI  - Long-term overexpression of membrane type-1 matrix metalloproteinase and matrix
      metalloproteinase-2 in oleic acid-induced pancreatitis in rats.
AB  - INTRODUCTION: The matrix metalloproteinase (MMP) plays important roles in
      extracellular matrix turnover. However, little is known about the roles of MMP-2
      and type IV collagen, and the relationship between MMP-2 and membrane type-1
      matrix metalloproteinase (MT1-MMP) during progressive destruction of acinar cells
      in pancreatitis. AIMS AND METHODOLOGY: To examine the serial changes in the
      expression and activity of MMP-2 and expression of MT1-MMP and tissue inhibitor
      of matrix metalloproteinase-2 (TIMP-2) in rats after induction of pancreatitis by
      intraductal infusion of oleic acid, and to determine protein concentrations by
      Western blot analysis and localization of type IV collagen by immunostaining.
      RESULTS: Gelatinolytic activity of pro-and active MMP-2 and concentrations of MT1
      MMP protein, as determined by zymography and Western blot analysis, respectively,
      increased significantly from 6 hours to day 42 after intraductal infusion of
      oleic acid. TIMP-2 mRNA expression was significantly higher than that at time 0
      throughout the study period, and gelatinolytic activity of active MMP-2 increased
      from day 3 to day 42. In addition, immunoreactivity for type IV collagen was
      detected as a discontinuous line along the basement membranes of ducts, vessels,
      tubular complexes, and acinar cells. CONCLUSION: Our findings indicate that long
      term increases of gelatinolytic activity of active MMP-2 cause continuous
      disorganization of type IV collagen in basement membranes during progressive
      atrophy of pancreatic gland in oleic acid-induced pancreatitis, and that MT1-MMP
      and TIMP-2 work as activating factors during proMMP-2 activation. Moreover,
      basement membranes disorganization in the sustentacula of acinar cells and duct
      epithelia seems to participate in continuous derangement of acinar cells and duct
      epithelium.

PMID- 11961488
TI  - Ultrasonographic splanchnic arterial flow measurement in severe acute
      pancreatitis.
AB  - INTRODUCTION: Duplex ultrasonographic technology is now capable of detecting flow
      signals in the various splanchnic vessels and calculating the concomitant flow
      velocities using fast-Fourier transformation. AIM: To use Doppler sonography to
      investigate how splanchnic hemodynamics vary during the early stage of severe
      acute pancreatitis. METHODOLOGY: Six patients with severe acute pancreatitis
      (age, 59.0 +/- 6.57 years; four men, two women) and seven with mild to moderate
      acute pancreatitis (age, 60.1 +/- 7.41 years; five men, two women) were examined
      with Doppler sonography immediately after disease onset. The maximum velocity,
      minimum velocity, mean velocity, pulsatility index, and resistive index were
      determined from the Doppler spectra from the proper hepatic artery, celiac
      artery, and superior mesenteric artery. We also examined 15 healthy subjects
      (age, 59.3 +/- 4.60 years; 10 men, five women) as controls. RESULTS: The maximum
      velocity of the proper hepatic artery in patients with severe acute pancreatitis
      was significantly higher than that in patients with mild to moderate acute
      pancreatitis (p = 0.011) and in control subjects (p = 0.0047). Similarly,
      significant increases in both the minimum velocity and the mean velocity of the
      proper hepatic artery were observed in patients with severe acute pancreatitis.
      Neither pulsatility index nor resistive index of the proper hepatic artery showed
      a significant difference among the three groups. There were no significant
      differences among the three groups with respect to the flow velocity of the
      superior mesenteric artery. In contrast, the pulsatility index of the superior
      mesenteric artery in patients with severe acute pancreatitis was significantly
      lower than that in patients with mild to moderate acute pancreatitis (p = 0.0058)
      or in control subjects (p = 0.0024). For patients with acute pancreatitis, a
      significant inverse correlation was obtained between the maximum velocity of the
      proper hepatic artery and the pulsatility index of the superior mesenteric artery
      (r = -0.658, p = 0.0145). CONCLUSION: The increase in the hepatic arterial flow
      velocity and the decrease in the superior mesenteric arterial pulsatility index
      may represent early events of the severe type of acute pancreatitis.

PMID- 11961489
TI  - Splenic atrophy in experimental severe acute pancreatitis.
AB  - INTRODUCTION: In severe acute pancreatitis, immunologic impairment is supposed to
      be linked to the development of subsequent infectious complications. AIM: To
      examine alterations of spleen in rat experimental severe acute pancreatitis.
      METHODOLOGY: Severe necrotizing pancreatitis was induced by retrograde injection
      of 3% sodium deoxycholate into the biliopancreatic ducts of male Wistar rats.
      RESULTS: In the rats with pancreatitis 12 and 24 hours after the induction,
      splenic weights were significantly lower than those of sham-operated rats.
      Numbers of splenocytes were also significantly reduced simultaneously. By in situ
      nick-end labeling, DNA fragmentation enzyme linked immunosorbent assay (ELISA),
      and DNA electrophoresis, no apoptosis was detected on the splenocytes from the
      rats with pancreatitis 6, 12, and 24 hours after the onset. Peripheral
      lymphocytes in the rats with pancreatitis were significantly decreased 6, 12, and
      24 hours after the onset compared with those in sham-operated rats. With
      antecedent splenectomy, peripheral lymphocyte counts 12 hours after the onset
      were significantly lower than those in rats who had not undergone splenectomy.
      Moreover, nuclear fragmentation was noted, and DNA fragments were significantly
      increased in peripheral lymphocytes at 6 hours in sodium deoxycholate
      pancreatitis. CONCLUSION: These results indicate that splenic atrophy resulting
      from splenocyte reduction occurs in rat experimental severe acute pancreatitis.
      It is suggested that splenocytes are recruited into systemic circulation in
      response to peripheral lymphocyte reduction as a result of apoptosis.

PMID- 11961490
TI  - Endogenous somatostatin inhibits interaction of insulin and cholecystokinin on
      exocrine secretion of isolated, perfused rat pancreas.
AB  - INTRODUCTION: Although somatostatin inhibits pancreatic exocrine secretion, the
      inhibitory mechanism of endogenous somatostatin is not clearly understood. AIM:
      To investigate the effect of endogenous somatostatin on the interaction between
      endogenous insulin and exogenous cholecystokinin (CCK) in exocrine secretion of
      the totally isolated, perfused rat pancreas. METHODOLOGY: Endogenous releases of
      somatostatin and insulin were induced by 18 mM glucose. Streptozotocin (75 mg/kg)
      or cysteamine (300 mg/kg) was injected into rats 24 hours before the experiment
      to deplete insulin or somatostatin in the pancreas. RESULTS: Glucose (18 mM)
      enhanced CCK (10 pM)-stimulated secretions of fluid and amylase in the normal
      pancreas, which was further elevated by a somatostatin antagonist. Exogenous
      insulin (100 nM) also enhanced CCK-stimulated secretions in the streptozotocin
      treated pancreas, which was also markedly increased by the somatostatin
      antagonist. The glucose (18 mM)-enhanced CCK-stimulated secretions were much
      higher in the cysteamine-treated pancreas than in the normal pancreas, which was
      dose-dependently reduced by exogenous somatostatin (30, 100 pM). However,
      endogenous or exogenous somatostatin did not modify the pancreatic responses to
      CCK alone. CONCLUSION: Endogenous somatostatin inhibits the interaction of
      endogenous insulin and CCK on pancreatic exocrine secretion in the rat rather
      than reducing the action of CCK alone or endogenous release of insulin.

PMID- 11961491
TI  - Insulin inhibits secretin-induced pancreatic bicarbonate output via cholinergic
      mechanisms.
AB  - INTRODUCTION: Exogenous insulin inhibits secretin-stimulated pancreatic
      bicarbonate output via a dose-dependent mechanism; this effect is prevented by
      pancreatic denervation. AIMS: To investigate possible cholinergic mediation, we
      examined the effect of bethanechol on secretin-stimulated pancreatic secretion
      during euglycemic, hyperinsulinemic clamp. METHODOLOGY: In four dogs with chronic
      pancreatic fistulas, euglycemic, hyperinsulinemic clamp (1.25 mU/kg/min) was
      begun after a 30-minute basal period; computer-assisted glucose administration
      maintained euglycemia. Control studies were performed with volume-matched and
      rate-matched vehicle infusion. After 1 hour, secretin infusion was begun at a
      dosage of 16 ng/kg/h; the dose was doubled every 30 minutes. The studies were
      then repeated during background bethanechol infusion (90 microg/kg/h) begun 30
      minutes after clamp initiation. Pancreatic juice was analyzed for bicarbonate and
      protein; serum samples were analyzed for glucose and insulin. RESULTS: Exocrine
      outputs and serum glucose and insulin levels did not differ in the basal period.
      Insulin levels were significantly elevated during the euglycemic,
      hyperinsulinemic clamp (62 microU/mL versus 12 microU/mL; p < 0.01); glucose
      levels did not differ. As before, secretin-induced bicarbonate output was
      inhibited by euglycemic, hyperinsulinemic clamp. The inhibitory effect of insulin
      was reversed by bethanechol. Despite the euglycemic, hyperinsulinemic clamp,
      secretin-induced bicarbonate output was potentiated by bethanechol at higher
      secretin doses (p < 0.05). CONCLUSION: These data confirm that cholinergic
      mechanisms mediate insulin's inhibition of secretin-induced pancreatic
      bicarbonate output.

PMID- 11961492
TI  - Role of the Gly40Ser mutation in the glucagon receptor gene in Brazilian patients
      with type 2 diabetes mellitus.
AB  - INTRODUCTION: A missense mutation in the glucagon receptor gene (Gly40Ser) has
      been associated with type 2 diabetes mellitus in some populations. AIM: To
      investigate whether this mutation is associated with type 2 diabetes in Brazilian
      patients and its functional significance in vivo. METHODOLOGY: One hundred
      fifteen patients with type 2 diabetes and 115 control subjects were screened by
      restriction-enzyme digestion with BstE II. The in vivo implications were
      investigated by 1 mg glucagon intravenous injection and plasma C-peptide (before
      and after 6 minutes) and glucose measurements (before and after 30, 60, 90, and
      120 minutes), and first-phase insulin response (1 + 3 minutes) to intravenous
      glucose tolerance test. These procedures were performed in two groups of patients
      with diabetes, which differed only by the presence or absence of the Gly40Ser
      mutation, and two groups of control subjects. RESULTS: The mutation was detected
      in two patients with diabetes (1.7%) and in four control subjects (3.5%) (not
      significant). Patients with diabetes and carriers of Gly40Ser showed basal C
      peptide levels significantly lower than noncarriers (0.70 ng/mL versus 1.50
      ng/mL, p = 0.008). No differences were found between Gly40Ser carriers and
      noncarriers in control subjects within the parameters studied. CONCLUSION: Our
      results show that the Gly40Ser mutation in the glucagon receptor gene is not
      associated with type 2 diabetes in a Brazilian population. However, a reduction
      of insulin secretion was observed in Gly40Ser carriers.

PMID- 11961493
TI  - International symposium: mechanism of pancreatitis--between bedside and
      laboratory.

PMID- 11961494
TI  - Cullen's sign in pancreatic trauma.

PMID- 11961495
TI  - Unusual presentation of pancreatic hydatid cyst in a child.

PMID- 11961496
TI  - Reason for performing endoscopic retrograde cholangiopancreatography (ERCP) and
      ES in a patient with severe gallstone pancreatitis even in the absence of main
      bile duct stones.

PMID- 11961497
TI  - A nested case-control study on risk of pancreatic cancer among workers in the
      rubber industry.

PMID- 11961498
TI  - [Growth disorders in Down's syndrome: growth hormone treatment].
AB  - BACKGROUND: The aim of the study was evaluate the short and long-term effects of
      growth hormone therapy in subjects affected by Trisomy 21. METHODS: The growth
      curves of 10 Down's syndrome patients (3 males and 7 females) aged between 21 and
      35 years old were analysed. During pre- or peripuberty these subjects had
      received growth hormone (GH) therapy lasting an average of 3.02 years. At
      distance of between 10 to 15 years after the end of GH therapy, routine
      laboratory tests (thyroid hormones, glycemia, glycosylated hemoglobin,
      transaminase) were carried out together with a full hematological assay
      (hemochrome using leukocyte formula, morphological study of blood components).
      RESULTS: GH therapy resulted in an increased rate of growth among these subjects
      and a improvement in final stature of 5.16 cm in males and 7.35 cm in females.
      The long-term controls did not reveal any hematological changes or changes in
      HbA1c concentrations, thyroid function and hepatic function, thus confirming the
      absence of collateral effects of GH therapy in subjects with Down's Syndrome.
      CONCLUSIONS: In view of these results, we are convinced that GH therapy is
      extremely positive in trisomy 21, given the marked improvements in terms of
      growth, the absence of collateral effects and the possible psychological benefits
      of increased stature, in particular a better insertion in society.

PMID- 11961499
TI  - [Prevalence and aggressiveness of thyroid carcinoma with diameter less than one
      centimetre in iodine deficiency areas].
AB  - BACKGROUND: The introduction of highly sensitive imaging techniques has made it
      possible to detect many non-palpable thyroid nodules with size less than 1
      centimetre. The prevalence of these lesions appears to be high in the general
      population and increases in iodine deficiency areas. Fine needle aspiration
      biopsy (FNAB) is considered the most reliable test for the diagnosis of thyroid
      nodules. METHODS: From January 1991 to December 2000, 6627 nodules were referred
      for FNAB to our department. In 4871 (73.5%) euthyroid patients the mean daily
      urinary excretion of iodine was 73+/-18 micromg/day. RESULTS: In 2401 nodules
      (36.2%) the diameter was less than one centimetre. Histologic confirmation of
      malignancy was available in 187 (89.9%) of 208 operated nodules with diameter
      more than 1 cm and in 64 (78%) of 82 with diameter less than 1 cm. Logistic
      regression analysis indicated that a solid hypoechoic feature was a useful
      criterion to predict malignancy (p<0.001), as well as the presence of
      calcification (p<0.5) and blurred margins (p<0.5). Lymph node metastases were
      present in 24.3% of carcinomas with diameter more than 1 cm but, surprisingly,
      also in 20.3% of those with diameter less than 1 cm. No correlation was seen
      between diameter of carcinoma nodules and presence of lymph node metastasis.
      CONCLUSIONS: These data suggest that the potential malignancy of thyroid nodules
      is not only correlated to the diameter but to other parameters such as the
      biological difference of thyroid cancer that could be hypothesized in an iodine
      deficiency area. In conclusion, FNAB is recommended for nodules with diameter
      less than 1 centimetre when sonographic findings suggest malignancy such as a
      hypoechoic pattern, an irregular margin or internal microcalcification.

PMID- 11961500
TI  - [Melatonin/circadian rhythm. Is there a feedback between epiphysis and
      hypophysis?].
AB  - BACKGROUND: The study evaluates the circadian rhythm of melatonin in relation to
      sex and age and identified contemporary alterations in the secreton of some
      hypophyseal hormones, suggesting that melatonin may exert a modulatory action on
      the latter. METHODS: The melatonin metabolite (6-hydroxymelatonin sulfate) was
      assayed in urine samples from 48 subjects of both sexes aged between 25 and 60
      years old using the RIA method described by Arendt, modified for the ise of
      iodine markers. A blood sample was taken from the same subjects to assay
      hypophyseal hormones. RESULTS: Melatonin secretion does not remain constant over
      24 hours in young subjects of both sexes, but instead is rhythmic. This rhythmic
      secretion is lacking in adults, revealing a daytime pineal secreton that is
      surprisingly higher than in younger persons. A difference in secretion levels was
      also found between sexes, a higher melatonin peak in females compared to males.
      Some young female subjects reveal a contemporary hypersecretion of the
      somatotropic hormone in line with the falling nocturnal peak of melatonin.
      Subjects with latent hypothyroidism show a diminished melatonin peak compared to
      that in euthyroid subjects. CONCLUSIONS: Changes in pineal secretion between the
      second and sixth decade of life are characterised by the loss of rhythmic
      secretion, linked not only to the loss of the nocturnal peak but an increased
      daytime secretion compared to younger subjects. The other finding that emerged
      from this study was the difference in secretion levels between the sexes. Lastly,
      we affirm that the pineal gland may exert a modulating influence on the
      hypophysis.

PMID- 11961501
TI  - The multifaceted potential of glucagon-like peptide-1 as a therapeutic agent.
AB  - Glucagon-like peptide-1 (GLP-1), an intestinal gut hormone, is rapidly emerging
      as a new therapeutic agent for the treatment of diabetes mellitus. GLP-1,
      released from intestinal L-cells, is renowned for its potent stimulation of
      insulin biosynthesis and release from pancreatic b-cells. Exogenous
      administration of GLP-1 to subjects with type 2 diabetes results in the
      normalization of plasma glucose concentrations, in part, as a result of augmented
      glucose-stimulated insulin secretion. However, it is now recognized that GLP-1
      has several other anti-diabetic actions that collectively improve the type 2
      diabetic phenotype, and may also prove beneficial in the treatment of type 1
      diabetes. These effects include the deceleration of gastric emptying and
      promotion of satiety, thereby reducing the availability of nutrients for
      absorption and reducing the requirement for insulin secretion. GLP-1 also reduces
      plasma glucose levels by suppressing glucagon secretion from pancreatic a-cells
      and potentially by improving insulin sensitivity in peripheral tissues. Further
      more, GLP-1 upregulates expression of b-cell genes (GLUT2, glucokinase, insulin,
      and PDX-1) and promotes b-cell neogenesis and differentiation of ductal cells
      into insulin secreting cells. Although initial clinical trials indicate GLP-1 has
      excellent therapeutic potential, its relatively short-lived biological activity
      and delivery difficulties limit its appeal. Several approaches that are currently
      being explored to overcome these limitations include mobilizing endogenous GLP-1
      release, preserving the biological activity of the native peptide, and developing
      GLP-1 analogues with extended durations of action.

PMID- 11961502
TI  - Biochemical and imaging evaluation of Cushing's syndrome.
AB  - The diagnosis and differential diagnosis of Cushing's syndrome remains a
      considerable challenge in clinical endocrinology. Investigation is a two-step
      process, involving first diagnosis followed by differential diagnosis.
      Traditionally diagnosis has relied upon urinary free cortisol (UFC) collection,
      low-dose dexamethasone-testing, and assessment of midnight cortisol. More
      recently, differentiation between mild disease and pseudo-Cushing's states has
      been achieved using dexamethasone-suppressed corticotropin releasing hormone
      (CRH) and desmopressin tests. Refinements of tests used for differential
      diagnosis have been made including optimized response criteria for ovine and
      human sequence CRH tests, desmopressin tests, GHBP-testing and testing with
      combinations of peptides. Despite improvements in these non-invasive tests use of
      inferior petrosal or cavernous sinus sampling is frequently required. Imaging is
      guided by biochemical assessment. MRI is the investigation of choice for
      Cushing's disease, but is often negative. Scintigraphic investigation using
      radionucleotide-labeled agonists for receptors commonly expressed by
      neuroendocrine tumors the investigation of occult ACTH-dependent disease remains
      disappointing. In this review we critically analyze the tests used for this most
      challenging of clinical conditions.

PMID- 11961503
TI  - [The management of thyrotoxicosis: a schematic approach].
AB  - Thyrotoxicosis is a well defined clinical entity, determined by an increase of
      plasma levels of thyroid hormones (T3 and T4). A number of causes of
      thyrotoxicosis are known, and it is therefore very important for the treatment to
      establish its etiology. In fact, metimazole or propylthiouracil are indicated for
      the thyrotoxic states caused by thyroid gland's hyperfunction (hyperthyroidism),
      but are not effective when thyrotoxicosis is determined by a follicular damage
      and disruption with leakage of preformed thyroid hormones, or in case of
      thyrotoxicosis factitia. Besides medical therapy, other two therapeutic options
      are available for the treatment of thyrotoxicosis: radioiodide administration
      (131I) and surgery. The physician can decide the best therapy on the basis of the
      following factors: etiology of thyrotoxicosis; patient's age and needs;
      presence/absence of concomitant diseases or pregnancy; presence of
      ophthalmopathy; goiter's size; advantages and disadvantages of each therapeutic
      option. A problem of particular regard is when and if to treat subclinical
      thyrotoxicosis (low TSH values, and normal plasma levels of thyroid hormones). On
      the basis of the natural history and of its consequences on the cardiovascular
      system and skeletal integrity, the authors propose to begin therapy whether
      subclinical thyrotoxicosis develop in the following four subgroups of subjects:
      patients with nodular goiter; women in post-menopause; patients with cardiac
      diseases; patients with osteoporosis.

PMID- 11961505
TI  - Hammerhead ribozymes designed to cleave all human rod opsin mRNAs which cause
      autosomal dominant retinitis pigmentosa.
AB  - PURPOSE: Knockdown hammerhead ribozymes were designed to cleave at a sterically
      accessible site in long expression-competent mutant and normal human rod opsin
      mRNAs. Ribozyme suppression of mutant mRNA is expected to rescue autosomal
      dominant retinitis pigmentosa (adRP) caused by rod opsin mutations. METHODS:
      Energy minimization algorithms predicted regions in human rod opsin mRNA
      accessible to ribozyme cleavage. Opsin and ribozyme RNAs were generated by in
      vitro transcription. Ribozyme cleavage reactions were performed in vitro at
      various enzyme:substrate ratios with appropriate controls and analyzed on
      denaturing polyacrylamide gels. RESULTS: A GUC triplet in a predicted
      unhybridized loop was selected as the target cleavage site. Ribozymes were
      designed to stabilize catalytic core folding. Ribozyme reactions with normal and
      representative mutant (C187Y) opsin mRNAs demonstrated a decrease of long and
      short RNA targets and proportional appearance of cleavage products. Site-specific
      targeting was proved by lack of cleavage of a normal mRNA engineered with a
      silently altered cleavage motif. CONCLUSIONS: Knockdown ribozymes, targeting all
      known adRP mutants, cleaved human rod opsin mRNAs at the intended target site in
      vitro. These ribozymes may reduce total opsin mRNA and protein in rod
      photoreceptors as a gene therapy strategy. A beneficial outcome on rod survival
      in adRP is expected although normal rhodopsin levels, already in excess, would
      also decrease. Knockdown ribozymes attack an accessible site common to all mutant
      mRNAs to avoid redesign and optimization for each new dominant mutation. This
      strategy can be extended to any dominant disease affecting genes normally
      expressed in excess.

PMID- 11961504
TI  - Tamoxifen, raloxifene and the prevention of breast cancer.
AB  - The recognition of a new group of drugs, now named selective estrogen receptor
      modulators (SERMs) has revolutionized prospects for the prevention of breast
      cancer. New agents will continue to be tested against tamoxifen, the first SERM
      and an established treatment of ER positive breast cancer. Raloxifene a related
      SERM is used to treat and prevent osteoporosis with the potential beneficial side
      effect of preventing breast cancer. The Study of Tamoxifen and Raloxifene (STAR)
      trial will establish whether raloxifene is an improvement over tamoxifen. Most
      importantly, emerging information about the molecular pharmacology of SERMs will
      be used to decipher the mechanism of action at specific target sites around a
      woman's body. This knowledge can be used to design new SERMs and advance the
      prospects for multifunctional medicine to prevent breast cancer, osteoporosis and
      coronary heart disease.

PMID- 11961506
TI  - Angiogenesis and antiangiogenic therapy.

PMID- 11961508
TI  - Biodefence research.

PMID- 11961509
TI  - Women don't want to be 'one of the boys'.

PMID- 11961510
TI  - NASA needs 'the vision thing'.

PMID- 11961511
TI  - Frogs put in the gender blender by America's favourite herbicide.

PMID- 11961513
TI  - Parkinson's patients show positive response to implants.

PMID- 11961515
TI  - Physicists blast US missile defence review.

PMID- 11961519
TI  - Conservationists under fire in the Philippines.

PMID- 11961522
TI  - Dengue virus: break-bone fever.

PMID- 11961523
TI  - Ukranian science: DIY, Kiev style.

PMID- 11961524
TI  - Work on weapons adds to public distrust of science.

PMID- 11961525
TI  - Mutation not universally linked with diabetes.

PMID- 11961526
TI  - Call for Elan to publish Alzheimer's trial details.

PMID- 11961527
TI  - Single-locus studies.

PMID- 11961533
TI  - Biological computation: amazing algorithms.

PMID- 11961534
TI  - Device physics: defective promise in photonics.

PMID- 11961536
TI  - Evolutionary biology: the tale of the parasitic cuckoos.

PMID- 11961535
TI  - Medicine: interfering with bone remodelling.

PMID- 11961537
TI  - Climate change: the 20-year forecast.

PMID- 11961538
TI  - DNA repair: breaking the seal.

PMID- 11961540
TI  - Astronomy: worlds of mutual motion.

PMID- 11961541
TI  - Microbiology: a resistance switch.

PMID- 11961543
TI  - Biodiversity: microbial genomes multiply.

PMID- 11961544
TI  - Green revolution: a mutant gibberellin-synthesis gene in rice.
AB  - The chronic food shortage that was feared after the rapid expansion of the world
      population in the 1960s was averted largely by the development of a high-yielding
      semi-dwarf variety of rice known as IR8, the so-called rice 'green revolution'.
      The short stature of IR8 is due to a mutation in the plant's sd1 gene, and here
      we identify this gene as encoding an oxidase enzyme involved in the biosynthesis
      of gibberellin, a plant growth hormone. Gibberellin is also implicated in green
      revolution varieties of wheat, but the reduced height of those crops is conferred
      by defects in the hormone's signalling pathway.

PMID- 11961545
TI  - Materials chemistry: macroporous crystalline vanadium oxide foam.
AB  - Porous inorganic solids can be synthesized in complex forms, and here we describe
      a simple method to create an ultralight, macroporous, crystalline vanadium oxide
      foam by bubbling oxygen gas produced in situ through a viscous vanadium oxide
      gel. This foaming process could be extended to other metal oxides.

PMID- 11961546
TI  - Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.
AB  - SCF complexes are the largest family of E3 ubiquitin-protein ligases and mediate
      the ubiquitination of diverse regulatory and signalling proteins. Here we present
      the crystal structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF complex, which shows
      that Cul1 is an elongated protein that consists of a long stalk and a globular
      domain. The globular domain binds the RING finger protein Rbx1 through an
      intermolecular beta-sheet, forming a two-subunit catalytic core that recruits the
      ubiquitin-conjugating enzyme. The long stalk, which consists of three repeats of
      a novel five-helix motif, binds the Skp1-F boxSkp2 protein substrate-recognition
      complex at its tip. Cul1 serves as a rigid scaffold that organizes the Skp1-F
      boxSkp2 and Rbx1 subunits, holding them over 100 A apart. The structure suggests
      that Cul1 may contribute to catalysis through the positioning of the substrate
      and the ubiquitin-conjugating enzyme, and this model is supported by Cul1
      mutations designed to eliminate the rigidity of the scaffold.

PMID- 11961547
TI  - The binary Kuiper-belt object 1998 WW31.
AB  - The recent discovery of a binary asteroid during a spacecraft fly-by generated
      keen interest, because the orbital parameters of binaries can provide measures of
      the masses, and mutual eclipses could allow us to determine individual sizes and
      bulk densities. Several binary near-Earth, main-belt and Trojan asteroids have
      subsequently been discovered. The Kuiper belt-the region of space extending from
      Neptune (at 30 astronomical units) to well over 100 AU and believed to be the
      source of new short-period comets-has become a fascinating new window onto the
      formation of our Solar System since the first member object, not counting Pluto,
      was discovered in 1992 (ref. 13). Here we report that the Kuiper-belt object 1998
      WW31 is binary with a highly eccentric orbit (eccentricity e approximately 0.8)
      and a long period (about 570 days), very different from the Pluto/Charon system,
      which was hitherto the only previously known binary in the Kuiper belt. Assuming
      a density in the range of 1 to 2 g cm-3, the albedo of the binary components is
      between 0.05 and 0.08, close to the value of 0.04 generally assumed for Kuiper
      belt objects.

PMID- 11961548
TI  - Electrical detection of spin precession in a metallic mesoscopic spin valve.
AB  - To study and control the behaviour of the spins of electrons that are moving
      through a metal or semiconductor is an outstanding challenge in the field of
      'spintronics', where possibilities for new electronic applications based on the
      spin degree of freedom are currently being explored. Recently, electrical control
      of spin coherence and coherent spin precession during transport was studied by
      optical techniques in semiconductors. Here we report controlled spin precession
      of electrically injected and detected electrons in a diffusive metallic
      conductor, using tunnel barriers in combination with metallic ferromagnetic
      electrodes as spin injector and detector. The output voltage of our device is
      sensitive to the spin degree of freedom only, and its sign can be switched from
      positive to negative, depending on the relative magnetization of the
      ferromagnetic electrodes. We show that the spin direction can be controlled by
      inducing a coherent spin precession caused by an applied perpendicular magnetic
      field. By inducing an average precession angle of 180 degrees, we are able to
      reverse the sign of the output voltage.

PMID- 11961549
TI  - Rapid electroplating of insulators.
AB  - Electrochemical techniques for depositing metal films and coatings have a long
      history. Such techniques essentially fall into two categories, with different
      advantages and disadvantages. The first, and oldest, makes use of spontaneous
      redox reactions to deposit a metal from solution, and can be used on both
      insulating and metallic substrates. But the deposition conditions of these
      processes are difficult to control in situ, in part because of the variety of
      salts and additives present in the solution. The second approach-electroplating
      uses an electric current to reduce metal ions in solution, and offers control
      over the quantity (and, to some extent, grain size) of deposited metal. But
      application of this technique has hitherto been restricted to conducting
      substrates. Here we describe an electroplating technique that permits coating of
      insulating substrates with metals having controlled grain size, thickness and
      growth speed. The basis of our approach is the progressive outward growth of the
      metal from an electrode in contact with the substrate, with the cell geometry
      chosen so that the electron current providing the reduction passes through the
      growing deposit. Such an approach would normally form dendritic or powdery
      deposits, but we identify a range of conditions in which uniform films rapidly
      form.

PMID- 11961550
TI  - Constraints on radiative forcing and future climate change from observations and
      climate model ensembles.
AB  - The assessment of uncertainties in global warming projections is often based on
      expert judgement, because a number of key variables in climate change are poorly
      quantified. In particular, the sensitivity of climate to changing greenhouse-gas
      concentrations in the atmosphere and the radiative forcing effects by aerosols
      are not well constrained, leading to large uncertainties in global warming
      simulations. Here we present a Monte Carlo approach to produce probabilistic
      climate projections, using a climate model of reduced complexity. The
      uncertainties in the input parameters and in the model itself are taken into
      account, and past observations of oceanic and atmospheric warming are used to
      constrain the range of realistic model responses. We obtain a probability density
      function for the present-day total radiative forcing, giving 1.4 to 2.4 W m-2 for
      the 5-95 per cent confidence range, narrowing the global-mean indirect aerosol
      effect to the range of 0 to -1.2 W m-2. Ensemble simulations for two illustrative
      emission scenarios suggest a 40 per cent probability that global-mean surface
      temperature increase will exceed the range predicted by the Intergovernmental
      Panel on Climate Change (IPCC), but only a 5 per cent probability that warming
      will fall below that range.

PMID- 11961551
TI  - Origins and estimates of uncertainty in predictions of twenty-first century
      temperature rise.
AB  - Predictions of temperature rise over the twenty-first century are necessarily
      uncertain, both because the sensitivity of the climate system to changing
      atmospheric greenhouse-gas concentrations, as well as the rate of ocean heat
      uptake, is poorly quantified and because future influences on climate-of
      anthropogenic as well as natural origin-are difficult to predict. Past
      observations have been used to help constrain the range of uncertainties in
      future warming rates, but under the assumption of a particular scenario of future
      emissions. Here we investigate the relative importance of the uncertainty in
      climate response to a particular emissions scenario versus the uncertainty caused
      by the differences between future emissions scenarios for our estimates of future
      change. We present probabilistic forecasts of global-mean temperatures for four
      representative scenarios for future emissions, obtained with a comprehensive
      climate model. We find that, in the absence of policies to mitigate climate
      change, global-mean temperature rise is insensitive to the differences in the
      emissions scenarios over the next four decades. We also show that in the future,
      as the signal of climate change emerges further, the predictions will become
      better constrained.

PMID- 11961552
TI  - Using the fossil record to estimate the age of the last common ancestor of extant
      primates.
AB  - Divergence times estimated from molecular data often considerably predate the
      earliest known fossil representatives of the groups studied. For the order
      Primates, molecular data calibrated with various external fossil dates uniformly
      suggest a mid-Cretaceous divergence from other placental mammals, some 90 million
      years (Myr) ago, whereas the oldest known fossil primates are from the basal
      Eocene epoch (54-55 Myr ago). The common ancestor of primates should be earlier
      than the oldest known fossils, but adequate quantification is needed to interpret
      possible discrepancies between molecular and palaeontological estimates. Here we
      present a new statistical method, based on an estimate of species preservation
      derived from a model of the diversification pattern, that suggests a Cretaceous
      last common ancestor of primates, approximately 81.5 Myr ago, close to the
      initial divergence time inferred from molecular data. It also suggests that no
      more than 7% of all primate species that have ever existed are known from
      fossils. The approach unites all the available palaeontological methods of timing
      evolutionary events: the fossil record, extant species and clade diversification
      models.

PMID- 11961553
TI  - Fisheries productivity in the northeastern Pacific Ocean over the past 2,200
      years.
AB  - Historical catch records suggest that climatic variability has had basin-wide
      effects on the northern Pacific and its fish populations, such as salmon,
      sardines and anchovies. However, these records are too short to define the nature
      and frequency of patterns. We reconstructed approximately 2,200-year records of
      sockeye salmon abundance from sediment cores obtained from salmon nursery lakes
      on Kodiak island, Alaska. Large shifts in abundance, which far exceed the decadal
      scale variability recorded during the past 300 years, occurred over the past two
      millennia. A marked, multi-centennial decline in Alaskan sockeye salmon was
      apparent from approximately 100 BC to AD 800, but salmon were consistently more
      abundant from AD 1200 to 1900. Over the past two millennia, the abundances of
      Pacific sardine and Northern anchovy off the California coast, and of Alaskan
      salmon, show several synchronous patterns of variability. But sardines and
      anchovies vary out of phase with Alaskan salmon over low frequency, which differs
      from the pattern detected in historical records. The coherent patterns observed
      across large regions demonstrate the strong role of climatic forcing in
      regulating northeastern Pacific fish stocks.

PMID- 11961554
TI  - Sexual conflict reduces offspring fitness in zebra finches.
AB  - Parental care is often costly; hence, in sexually reproducing species where both
      male and female parents rear their offspring (biparental care), sexual conflict
      over parental investment can arise. Such conflict occurs because each care-giver
      would benefit from withholding parental investment for use with another partner,
      leading to a reduction in the amount of care given by one parent at the expense
      of the other. Here we report experiments to explore the prediction from theory
      that parents rearing offspring alone may provide greater parental investment than
      when rearing offspring together with a partner. We found that when the number of
      offspring per parent, and hence the potential workload, were kept constant,
      offspring received a greater per capita parental investment from single females
      than from both parents working together, and that males reared by single mothers
      were more sexually attractive as adults than their biparentally reared siblings.
      This difference between single- and two-parent families is due to a reduction in
      care provided by females when they care together with a male, rather than
      laziness by males or differences in the begging behaviour of chicks, supporting
      the claim that sexual conflict in biparental care can reduce the quality of
      offspring raised.

PMID- 11961555
TI  - Direct cortical input modulates plasticity and spiking in CA1 pyramidal neurons.
AB  - The hippocampus is necessary for the acquisition and retrieval of declarative
      memories. The best-characterized sensory input to the hippocampus is the
      perforant path projection from layer II of entorhinal cortex (EC) to the dentate
      gyrus. Signals are then processed sequentially in the hippocampal CA fields
      before returning to the cortex via CA1 pyramidal neuron spikes. There is another
      EC input-the temporoammonic (TA) pathway-consisting of axons from layer III EC
      neurons that make synaptic contacts on the distal dendrites of CA1 neurons. Here
      we show that this pathway modulates both the plasticity and the output of the rat
      hippocampal formation. Bursts of TA activity can, depending on their timing,
      either increase or decrease the probability of Schaffer-collateral (SC)-evoked
      CA1 spikes. TA bursts can also significantly reduce the magnitude of synaptic
      potentiation at SC-CA1 synapses. The TA-CA1 synapse itself exhibits both long
      term depression (LTD) and long-term potentiation (LTP). This capacity for bi
      directional plasticity can, in turn, regulate the TA modulation of CA1 activity:
      LTP or LTD of the TA pathway either enhances or diminishes the gating of CA1
      spikes and plasticity inhibition, respectively.

PMID- 11961556
TI  - Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic
      variation.
AB  - Colonization of the lungs of cystic fibrosis (CF) patients by the opportunistic
      bacterial pathogen Pseudomonas aeruginosa is the principal cause of mortality in
      CF populations. Pseudomonas aeruginosa infections generally persist despite the
      use of long-term antibiotic therapy. This has been explained by postulating that
      P. aeruginosa forms an antibiotic-resistant biofilm consisting of bacterial
      communities embedded in an exopolysaccharide matrix. Alternatively, it has been
      proposed that resistant P. aeruginosa variants may be selected in the CF
      respiratory tract by antimicrobial therapy itself. Here we report that both
      explanations are correct, and are interrelated. We found that antibiotic
      resistant phenotypic variants of P. aeruginosa with enhanced ability to form
      biofilms arise at high frequency both in vitro and in the lungs of CF patients.
      We also identified a regulatory protein (PvrR) that controls the conversion
      between antibiotic-resistant and antibiotic-susceptible forms. Compounds that
      affect PvrR function could have an important role in the treatment of CF
      infections.

PMID- 11961558
TI  - Cells compete for decapentaplegic survival factor to prevent apoptosis in
      Drosophila wing development.
AB  - During the growth of Drosophila imaginal discs a process called 'cell
      competition' eliminates slow-proliferating but otherwise viable cells. We report
      here that cell competition requires the function of the brinker (brk) gene, whose
      expression is normally repressed by Decapentaplegic (Dpp) signalling but is
      upregulated in slow-growing Minute/+ cells. Excess brk expression activates the c
      Jun amino-terminal kinase pathway, which in turn triggers apoptosis in these
      cells. We propose that slow-proliferating cells upregulate Brk levels owing to a
      disadvantage in competing for, or in transducing, the Dpp survival signal. This
      sequence of events might represent a general mechanism by which weaker cells are
      eliminated from a growing population, and might serve as a method of controlling
      cell number and optimizing tissue fitness and hence organ function.

PMID- 11961557
TI  - RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon
      beta.
AB  - Osteoclasts are cells of monocyte/macrophage origin that erode bone matrix:
      regulation of their differentiation is central to the understanding of the
      pathogenesis and treatment of bone diseases such as osteoporosis. Signalling by
      RANKL (receptor activator of NF-kappaB ligand), also known as Tnfsf11, is
      essential for the induction of osteoclast differentiation, and it must be
      strictly regulated to maintain bone homeostasis. But it is not known whether
      RANKL signalling to the cell interior is linked to any regulatory mechanisms.
      Here we show that RANKL induces the interferon-beta (IFN-beta) gene in osteoclast
      precursor cells, and that IFN-beta inhibits the differentiation by interfering
      with the RANKL-induced expression of c-Fos, an essential transcription factor for
      the formation of osteoclasts. This IFN-beta gene induction mechanism is distinct
      from that induced by virus, and is dependent on c-Fos itself. Thus an
      autoregulatory mechanism operates-the RANKL-induced c-Fos induces its own
      inhibitor. The importance of this regulatory mechanism for bone homeostasis is
      emphasized by the observation that mice deficient in IFN-beta signalling exhibit
      severe osteopenia (loss of bone mass) accompanied by enhanced osteoclastogenesis.
      Our study places the IFN-beta system in a new context, and may offer a molecular
      basis for the treatment of bone diseases.

PMID- 11961559
TI  - SWAP-70 is a guanine-nucleotide-exchange factor that mediates signalling of
      membrane ruffling.
AB  - Phosphoinositide-3-OH kinase (PI(3)K), activated through growth factor
      stimulation, generates a lipid second messenger, phosphatidylinositol-3,4,5
      trisphosphate (PtdIns(3,4,5)P3). PtdIns(3,4,5)P3 is instrumental in signalling
      pathways that trigger cell activation, cytoskeletal rearrangement, survival and
      other reactions. However, some targets of PtdIns(3,4,5)P3 are yet to be
      discovered. We demonstrate that SWAP-70, a unique signalling protein,
      specifically binds PtdIns(3,4,5)P3. On stimulation by growth factors, cytoplasmic
      SWAP-70, which is dependent on PI(3)K but independent of Ras, moved to cell
      membrane rearrangements known as ruffles. However, mutant SWAP-70 lacking the
      ability to bind PtdIns(3,4,5)P3 blocked membrane ruffling induced by epidermal
      growth factor or platelet-derived growth factor. SWAP-70 shows low homology with
      Rac-guanine nucleotide exchange factors (GEFs), and catalyses PtdIns(3,4,5)P3
      dependent guanine nucleotide exchange to Rac. SWAP-70-deficient fibroblasts
      showed impaired membrane ruffling after stimulation with epidermal growth factor,
      and failed to activate Rac fully. We conclude that SWAP-70 is a new type of Rac
      GEF which, independently of Ras, transduces signals from tyrosine kinase
      receptors to Rac.

PMID- 11961560
TI  - A proteasomal ATPase subunit recognizes the polyubiquitin degradation signal.
AB  - The 26S proteasome is the chief site of regulatory protein turnover in eukaryotic
      cells. It comprises one 20S catalytic complex (composed of four stacked rings of
      seven members) and two axially positioned 19S regulatory complexes (each
      containing about 18 subunits) that control substrate access to the catalytic
      chamber. In most cases, targeting to the 26S proteasome depends on tagging of the
      substrate with a specific type of polyubiquitin chain. Recognition of this signal
      is followed by substrate unfolding and translocation, which are presumably
      catalysed by one or more of six distinct AAA ATPases located in the base-a ring
      like 19S subdomain that abuts the axial pore of the 20S complex and exhibits
      chaperone activity in vitro. Despite the importance of polyubiquitin chain
      recognition in proteasome function, the site of this signal's interaction with
      the 19S complex has not been identified previously. Here we use crosslinking to a
      reactive polyubiquitin chain to show that a specific ATPase subunit, S6' (also
      known as Rpt5), contacts the bound chain. The interaction of this signal with 26S
      proteasomes is modulated by ATP hydrolysis. Our results suggest that productive
      recognition of the proteolytic signal, as well as proteasome assembly and
      substrate unfolding, are ATP-dependent events.

PMID- 11961565
TI  - [Evaluation and nutritional therapy in cirrhotic patients of the "Edgardo
      Rebagliati Martins" hospital].
AB  - A nutritional evaluation was carried out in 43 cirrhotic outpatients who came to
      the Digestive Disease Department of the Edgardo Rebagliati Martins Hospital for a
      checkup. The evaluation included a dietary composition analysis; nutritional
      status through the analysis of lean and fatty mass through anthropometric
      parameters (tricipital skin fold thickness, midarm muscle circumference, muscle
      arm circumference and creatinine excretion in the 24 h urine/height ratio),
      measuring of visceral proteins (albumin, transferrin) and bioelectric Impedance.
      Finally, a nutritional dietary intervention was made according to international
      standards for cirrhotic patients. The Child - Pugh score was: Child A: 16
      patients (37.1%), Child B: 20 patients (46.5%) and Child C: 7 patients (16.4%).
      The dietary analysis showed the following: Hypoprotein diets in 42 patients
      (98%), hypocaloric diets in 38 patients (88%), low fat diets in 36 patients
      (83.7%) only one patient had a normal diet. Nutritional status was normal in 15
      patients (35%), 24 patients had protein malnutrition (56%) and 4 patients had
      protein-calorie malnutrition (9.3%). There was an association between Child B and
      C and the malnutrition diagnosis was (p = 0.045). The nutritional intervention
      was carried out in 19 of the 43 patients (dietary therapy) during 15 months; the
      results were 17 hospital admissions in the group without nutritional intervention
      and 6 in the group that had received nutritional intervention: (p = 0.01).
      Malnutrition and inadequate diets are becoming a prevalent problem in our
      cirrhotic population. Nutritional support may provide an additional and valuable
      therapy to decrease patient morbidity.

PMID- 11961561
TI  - Geobacter metallireducens accesses insoluble Fe(III) oxide by chemotaxis.
AB  - Microorganisms that use insoluble Fe(III) oxide as an electron acceptor can have
      an important function in the carbon and nutrient cycles of aquatic sediments and
      in the bioremediation of organic and metal contaminants in groundwater. Although
      Fe(III) oxides are often abundant, Fe(III)-reducing microbes are faced with the
      problem of how to access effectively an electron acceptor that can not diffuse to
      the cell. Fe(III)-reducing microorganisms in the genus Shewanella have resolved
      this problem by releasing soluble quinones that can carry electrons from the cell
      surface to Fe(III) oxide that is at a distance from the cell. Here we report that
      another Fe(III)-reducer, Geobacter metallireducens, has an alternative strategy
      for accessing Fe(III) oxides. Geobacter metallireducens specifically expresses
      flagella and pili only when grown on insoluble Fe(III) or Mn(IV) oxide, and is
      chemotactic towards Fe(II) and Mn(II) under these conditions. These results
      suggest that G. metallireducens senses when soluble electron acceptors are
      depleted and then synthesizes the appropriate appendages to permit it to search
      for, and establish contact with, insoluble Fe(III) or Mn(IV) oxide. This approach
      to the use of an insoluble electron acceptor may explain why Geobacter species
      predominate over other Fe(III) oxide-reducing microorganisms in a wide variety of
      sedimentary environments.

PMID- 11961567
TI  - [Fasciolasis in Cajamarca].
AB  - This study is descriptive and retrospective. It is based on the review of
      clinical and surgery records at the Hospital Regional de Cajamarca from April
      1996 to March 2001. 101 cases, positive for fasciolasis in feaces, were analyzed,
      62% were under 19 years of age; the male/female ratio was 1:2. The most frequent
      symptom was abdominal pain (84,5%). The duration of the disease was of less than
      three months (43,5%). 48% of the patients had eosinophilia. After rewiewing 162
      postcholecystectomy patients, we found Fasciola hepatica in 1,2%. Moreover, one
      patient of this group was operated because of an intrahepatic hematoma before the
      fasciolasis diagnose. It was concluded that fasciolasis was still an endemic
      illness in Cajamarca.

PMID- 11961566
TI  - [Clinic-pathologic pattern and survival range in resectable gastric carcinoma].
AB  - The present retrospective study evaluated 180 patients with resectable (Group I )
      and 128 patients with unresectable (Group II) gastric carcinoma at Belen
      Hospital, Trujillo, Peru, from 1966 to 1998, with the aim to identify the
      clinical and pathological features, actuarial survival rate and surgical
      morbidity and mortality rates of both groups. The mean age of the total series
      was of 58.3 + 14.8 years (range, 18 to 85 years). The most frequent symptoms in
      both groups were abdominal pain (89.4% and 94.5% respectively) and the most
      common sign was pallor (62.8% and 54.5% respectively). The unresectable cases
      presented a higher frequency of palpable mass (p<0.001), upper two thirds
      neoplasms (p=0.0032), T4 lesions (p<0.001), distant metastasis (p<0.001), stage
      IV (p<0.001), hepatic metastasis (p<0.001) and peritoneal metastasis (p<0.001),
      compared with resectable gastric cancer patients. The total surgical mortality
      rate was of 19.5% (Group I: 12.1%, Group II: 28.9%). The most frequent
      complications were pneumonia (Group I: 8.9%, Group II: 7.8%) and surgical wound
      infection (Group I: 10.6%, Group II: 3.9%). In Group II, the exploratory
      laparotomy was carried out in 82 cases, whilst 46 cases underwent
      gastroenterostomy (n=34), gastrostomy (n=6), gastrectomy by exclusion (n=5) and
      ileotransversoanastomosis (n=1). The 5-year survival rate in resectable patients
      was of 18.5% and in unresectable cases the survival rate at 12 and 36 months was
      of 9% and 0% respectively. The early diagnosis of this neoplasm, mainly in high
      risk patients, would offer better possibilities of an opportune treatment.

PMID- 11961568
TI  - [Early complications of endoscopic retrograde cholangiopancreatography performed
      from January 1998 to December 2000 at the Daniel Alcides Carrion National
      Hospital "ELCALLAO", Peru].
AB  - OBJECTIVES: The aim of this study was to determine the procedure characteristics
      of ERCP, indications and frequency of complications, as well as analyzing the
      associated risk factors. METHODS: ERCPs carried out from January 1998 to December
      2000 in the Gastroenterology Service of Daniel Alcides Carri n Hospital were
      evaluated retrospectively; 17 risk factors were analyzed. RESULTS: A total of 202
      ERCPs were carried out in 182 patients, of which 70.3% were patients aged under
      60 years and 66.5% were female patients. The most frequent indication was bile
      duct stone suspect (59.4%). Therapeutic ERCPs were carried out in 49.5% of total
      ERCPs, diagnostic ERCPs were 33.2%, and failure ERCPs 17.3%. Post-ERCP
      complications occurred in 5.9% (12 cases), and the most frequent were: acute
      pancreatitis 3.4% and hemorrhage 1%. There was no mortality case related with
      complications. A risk factor related with the procedure: pancreatic cannulation
      or pancreatic contrast injections reached the highest statistic significance (p=
      0.063). Therapeutic or failed ERCPs presented significant higher frequency of
      complications than diagnostic ERCPs: (p=0.0085 and p=0.0381). CONCLUSIONS: the
      frequency of early post-ERCP complications is 5.9%, and has a direct relation
      with therapeutic or failed ERCPs. This marks a difference with regards to
      diagnostic ERCPs. There was no mortality, and pancreatic cannulation or
      pancreatic contrast injections would be able to determine the development of
      complications.

PMID- 11961569
TI  - [Barrett's esophagus].
AB  - The first part of this report reviews the definition, history and clinical
      aspects of Barrett s Esophagus. The next section explains the results obtained at
      INEN, Lima Peru. The first case of Barrett s Esophagus complicated with
      Adenocarcinoma was diagnosed in 1956. The prevalence of Barrett s Esophagus in
      3,904 patients who were administered endoscopy examinations is 0.64%. The
      evaluation of 40 patients with Barrett s Esophagus indicated that it has a
      greater incidence in males than in females (3:1). The average age of patients
      with Barrett s Esophagus is 60 years and its incidence increases as they grow
      older. It manifests itself in 40 year old persons and is specially strong from 55
      to 64 years of age. Dysplasia is associated with Intestinal Metaplasia. The
      frequency of the epidermoid carcinoma is of 96% and for adenocarcinoma of 4% in
      the period of evaluation of 15 years (1985-1999). There is no difference in the
      tendency of epidermoid carcinoma and esophagus adenocarcinoma during the same
      evaluation period. The incidence of Barrett s Esophagus adenocarcinoma is higher
      in males than in females: (6:1). Intestinal metaplasia is found in 13/14 patients
      evaluated in relation to the esophagus adenocarcinoma. Long segment Barrett s
      Esophagus, is found in 13/14 patients complicated with adenocarcinoma. The
      average size of the long segment Barrett s Esophagus is of 6 cm in the patients
      with adenocarcinoma.

PMID- 11961570
TI  - [Functional nutrients, digestive tract and potencial benefits for the child].
AB  - Widespread interest in the possibility that selected foods containing
      specifically physiologically active components might promote health has resulted
      in the coining of the term Functional Food. Recent studies have shown that
      modified foods or selected ingredients may provide health benefits. Benefits
      touted by these foods are known to prevent certain diseases, promote health or
      both; and by that promoting a state of well-being and better health; reducing the
      risk of disease. The gastrointestinal tract is an obvious target for the
      development of Functional Foods, acting as it does as the interface between diet
      and the metabolic events, which sustain life. The American Dietetic Association
      recommends cautious evaluation of the clinical efficacy of individual
      nutrients/ingredients before recommending their use to promote as specific health
      outcome. Identification of sensitive and reliable biomarkers will be key to
      adequate assessment of the true effect of foods and their components.

PMID- 11961571
TI  - [Wilson'S disease: dominant neuropsychiatric form. Case presentation and its
      physiopathologic interpretation based upon magnetic resonance of the encephalon].
AB  - This is a presentation of a clinical case of Wilson s disease. The patient is a
      26 year old woman who began to evidence psychological symptoms, which were later
      accompanied by neurological manifestations such as asymmetrical hand tremor,
      parkinsonism, dystonia and later on, dysphagia and mutism. The ophthalmological
      examination found a Kayser Fleischer ring in Descemet s membrane. There was
      disturbance of copper metabolism documented with reduction of serum ceruloplasmin
      and increase of the urinary excretion of copper. Cirrhosis was demonstrated
      through laparoscopy and liver biopsy. The brain magnetic resonance showed
      frontotemporal atrophy and a degenerative process at the basal ganglia,
      cerebellum and brain stem. This information could suggest probable
      neuropsychiatric physiopathology. The stenosis and intense cervical dysphagia,
      associated with the crycopharyngeal membrane, has not been mentioned previously.

PMID- 11961572
TI  - [Pancreas divisum: endoscopic management. Case report].
AB  - This is a case report of a 19 year-old woman, with an acute recurrent
      pancreatitis diagnose, and pancreas divisum as anatomic alteration. An extensive
      evaluation including specialized labs, ERCP was done. The diagnosis is suspected
      during ERCP and confirmed by minor papilla injection. Treatment is directed
      towards relieving outflow obstruction at the level of the minor papilla, with
      successful results.

PMID- 11961573
TI  - [Erythrocytosis associated with hepatocellular carcinoma. Two case reports].
AB  - Erythrocytosis is a well-known paraneoplastic syndrome of hepatocellular
      carcinoma (HCC), occurring in 1% of cases of this neoplasm. This report describes
      two HCC patients who manifested erythrocytosis in their clinical report. Similar
      features found in both patients were a large tumour burden, high concentration of
      hemoglobin and hematocrit, increased levels of serum alphafetoprotein (AFP) and
      positive HBsAg. Right lobectomy of the liver was performed. Histological findings
      of the specimen showed HCC of trabecular pattern. Hemoglobin and hematocrit
      returned to normal range after the operation.

PMID- 11961574
TI  - [Antiarrhythmic and antioxidative effects of intermittent hypoxia exposure on rat
      myocardium].
AB  - The purpose of the study was to observe the effects of intermittent hypoxia
      exposure (IH) on the arrhythmia and antioxidation with ligation of coronary
      artery of rat heart together with measuring SOD (superoxide dismutase) and MDA
      (malondialdehyde) in myocardium. Comparison with continued hypoxia exposure was
      also made. The results obtained are as follows. (1) Arrhythmia scores of ischemic
      arrhythmia and reperfusion arrhythmia observed in the rats treated with IH 28-day
      (IH28) and 42-day (IH42), one week (IH28-1W) and two weeks (IH28-2W) after 28-day
      IH, as well as in those with continued hypoxia 28-day (CH28) and 42-day (CH42),
      were significantly lower than controls. (2) SOD in IH28, IH42, CH28, CH42, IH28
      1W, IH28-2W and three weeks after 28-day IH were significantly higher than
      controls; MDA in IH14, IH28, IH42, CH28, CH42, IH28-1W and IH28-2W were
      significantly lower than controls. It is suggested that IH for 28 or 42 days has
      some definite antiarrhythmic effect against ischemia and reperfusion, which was
      related to the strength of antioxidation in myocardium. The antiarrhythmic
      effects occurred gradually after 14 days IH and persisted for about two weeks
      after 28 days IH.

PMID- 11961575
TI  - [Evaluation of G(i/o) protein signal transduction pathway in cardioprotection of
      hypoxic preconditioning].
AB  - In order to understand the intracellular mechanism of hypoxic preconditioning,we
      investigated the effects of G(i/o) protein, phospholipase C and adenylyl
      cyclase/cyclic adenosine monophosphate (cAMP) on the survival rate and lactate
      dehydrogenase (LDH) release of cultured neonatal rat cardiomyocytes during the
      reoxygenation following 3 h of hypoxia. Cardioprotection was conferred by a brief
      episode of hypoxia followed by reoxygenation. The obtained results are as
      follows: (1) Hypoxic preconditioning (25 min of hypoxia and 30 min of
      reoxygenation) increased the survival rate and decreased the release of LDH in
      the myocytes suffering from sustained hypoxia-reoxygenation. (2) Reducing the
      intracellular cAMP by N-ethylmaleimide, an inhibitor of adenylyl cyclase, could
      mimic the cardioprotection of the preconditioning. (3) Inhibition of G(i/o)
      protein by pertussis toxin abolished the cardioprotection of hypoxic
      preconditioning, with reduction of the survival rate and increase of the release
      of LDH. (4) U-73122 could not abolish the protective effect of hypoxic
      preconditioning. (5) When intracellular cAMP was increased by using 8-Br-cAMP, a
      high membrane permeable cAMP analogue, or forskolin, a specific adenylyl cyclase
      activator, the survival rate was lower and LDH activity higher than those in
      preconditioning myocytes. The results indicate that G(i/o) protein is a crucial
      component, in cardioprotection of hypoxic preconditioning in neonatal rat
      cardiomyocytes. Activation of phospholipase C does not seem to be involved in the
      intracellular signal pathway underlying the cardioprotective effect of the
      preconditioning.

PMID- 11961576
TI  - [Ion channels in rat pancreatic beta cells].
AB  - Using perforated and cell-attached patch clamp techniques, the characteristics of
      ATP sensitive K(+) channels (K(ATP)), delayed rectifier K(+) channels (K(DR)),
      Ca(2+) and Na+ channels on single rat pancreatic beta cell membranes were
      studied. The results showed that (1) the efflux and influx conductance of K(ATP)
      channels was about 31 and 65 pS respectively, and the reversal potential of
      K(ATP) was about   60 mV; (2) K(DR) was activated completely after a latency of
      20 ms, and K(DR) was about 1/3 of K(ATP); (3) whole cell Ca(2+) current reached a
      peak (40  60 pA) at 0 mV; L-type Ca(2+) channel was the main Ca(2+) channel in
      beta cells, but other types of high voltage activated Ca(2+) channels existed as
      well; and   4) whole cell Na(+) current reached a peak (200  400 pA) at 10 mV;
      but the expression level of Na(+) channel in beta cells varied among the cells.
      About half of the beta cells virtually had no Na(+) currents.

PMID- 11961577
TI  - Role of renal medullary inducible nitric oxide synthase in the regulation of
      arterial pressure.
AB  - In the present work, we have examined the effects of selective inhibition of the
      inducible isoform of nitric oxide synthase (iNOS) in rat medulla by
      aminoguanidine (AG) on the arterial pressure of Dahl salt sensitive (DS), Dahl
      salt-resistant (DR) and Sprague Dawley (SD) rats by chronic in vivo hemodynamic
      experiment, the effect of sodium chloride (NaCl) or NaCl plus AG infusion on
      urinary nitrate/nitrite (urinary NO3/NO2  UNO(x)), the end product of nitric
      oxide (NO), excretion, glomerular filtration rate (GFR), effective renal plasma
      flow (ERPF) and plasma renin activity (PRA). Furthermore, an iNOS activity assay
      was also made. The results showed that AG infusion significantly augmented the
      pressor response of DS and SD rats to high NaCl (8%) intake, and decreased GFR,
      ERPF and PRA of DS rats. In addition, in DS rats, renal medullary interstitial
      administration of high NaCl significantly elevated the iNOS activity of renal
      tissue, especially inner medulla and outer medulla, and greatly increased UNO(x)
      excretion. Therefore, it is concluded that inducible NOS is an important
      modulator of blood pressure in case of NaCl-induced hypertension.

PMID- 11961578
TI  - [Cell activities in primate areas F2 and F4 of the monkey during memorized
      spatial motor task].
AB  - Single-cell activities were recorded in the area F2 of dorsal premotor cortex
      (PMd) and area F4 of ventral premotor cortex (PMv) while a monkey was performing
      a memorized spatial motor task of sequence (MSS). For the task of MSS-G, using
      green light as a cue during the cue period, 78.2% and 41.5% of the task-related
      neurons exhibited changes in activities in the areas F2 and F4, respectively( 
      (2)  15.2, P<0.005), whereas there were more neurons exhibiting changes in
      activities in F4 than in F2 during the image and the touch periods. The
      differences were both statistically significant. Similar results were obtained
      for the task of MSS-R using red light as a cue. Furthermore, there were more
      cells responding to the cue signal in F2 than in F4, while the situation was
      reversed during the image and touch periods. The present findings indicate that
      neurons in the PMd and PMv examined are differentially involved in the MSS task.

PMID- 11961579
TI  - [Interaction between pelvic and pudendal afferent inputs in lumbar-sacral spinal
      cord in rats].
AB  - Time-dependent inhibition is one of the means to study the interactions between
      peripheral inputs. The present study was performed on anesthetized and paralyzed
      Wistar rats using the technique of conditioning-testing stimulation. Electric
      stimulation (1.5 3 folds of the threshold intensity) was given to pelvic and
      pudendal nerves. Extracellular recordings were made from convergent neurons at
      L(6)-S(1) segments of the spinal dorsal horn. Stimulus intervals between
      conditioning and testing stimulation were measured when a half of the testing
      responses were inhibited by conditioning responses or the inhibition just began
      to occur. The time-dependent inhibition was seen in neurons situated deeper than
      300 m beneath the dorsal surface of the spinal cord, and not in more superficial
      neurons. The inhibition intervals were in the range of 1 360 ms and became longer
      when conditioning stimulation was given to the pelvic nerve. The inhibition
      intervals were 1 3 ms in superficial neurons (<300 micrometer) and no apparent
      time-dependent inhibition occurred. The inhibition in deeper neurons was
      partially reduced by cold block conducted at segments C(5-6) and the blockage was
      more significant when conditioning stimulation was applied to the pelvic nerve.
      These findings suggest that the inputs from the pelvic and pudendal nerves may
      converge on single neurons at deeper lumbosacral dorsal horn and the pudendal
      nerve induced responses are more likely to be inhibited in these neurons, which
      may be further strengthened by superspinal structures.

PMID- 11961580
TI  - [Ketamine and L-NAME inhibit NOS and somatostatin mRNA expression induced by
      altitude hypoxia in the rat hypothalamus].
AB  - Using altitude hypoxia model, in situ hybridization and NADPH-d histochemistry,
      we investigated the effects of ketamine and L-NAME (blocker of NOS) on NOS and
      somatostatin mRNA (SS mRNA) expression in the rat hypothalamus following acute
      altitude hypoxia. It was revealed that acute altitude hypoxia induced NOS and SS
      mRNA overexpression in the rat hypothalamus. When pretreated with NMDA receptor
      antagonist ketamine and L-NAME, NOS and SS mRNA expression were inhibited
      significantly. These results suggest that NMDA receptor activation participates
      in the expression of NOS and SS mRNA in the rat hypothalamus subjected to acute
      altitude hypoxia. Meanwhile, hypothalamic endogenous NO may mediate expression of
      SS mRNA.

PMID- 11961581
TI  - Electrophysiological study on biphasic firing activity elicited by D(1) agonistic
      D(2) antagonistic action of (-)-stepholidine in nucleus accumbens.
AB  - Our previous work has demonstrated that (-)-stepholidine (SPD) has dual action,
      ie D(1) agonistic-D(2) antagonistic action on DA receptors in the nigra-striatal
      dopamine (DA) system. The present study attempted to ascertain its dual action on
      the mesolimbic DA system. The firing activities of the nucleus accumbens (NAc)
      neurons were extracellularly recorded with intravenous and iontophoretic
      administration of the drug in 6-hydroxydopamine (6-OHDA)-lesioned and intact
      rats. The results showed that SPD produced a consistently biphasic firing of NAc
      neurons during the cumulative doses of 0.02  2 mg/kg, iv. When the rats were
      pretreated with D(2) antagonist spiperone, SPD only exerted an increasing effect,
      which was subsequently reversed by the D(1) antagonist SCH-23390. Moreover, SCH
      23390 could prevent the rate of increase elicited by SPD at high doses,
      presumably due to the D(1) agonistic action of SPD on the activity of NAc neuron.
      On the other hand, the inhibition of NAc firing elicited by either D(2) agonist
      LY171555 or D(1)/D(2) agonists apomorphine was completely reversed by SPD,
      suggesting an antagonistic action of SPD to D(2) receptors. In 6-OHDA-lesioned
      rats, iontophoresis of SPD also had an inhibitory effect in the majority of NAc
      neurons (91%) as SKF-38393 did. This inhibition could be completely blocked by
      the ejection of SCH-23390, but not by spiperone. These results indicate that SPD
      also has a D(1) agonistic-D(2) antagonistic dual action on NAc neuron activity,
      which may be beneficial to the treatment of schizophrenia.

PMID- 11961582
TI  - [The role of somatostatin in area CA1 of rat hippocampus in experimental
      epilepy].
AB  - In area CA1, intrahippocampal microinjection of somatostatin(SS, 0.03 to 0.3
      nmol) caused single or a series of spike-sharp waves in the cortex
      electroencephalogram (EEG), the spectrum average total power of which is
      increased dose-dependently from 0.006 to 0.15 nmol. Microinjection of SS into the
      hippocampal CA1 subregion brought out epileptic-like behavioral responses and
      aggregated kainic acid (KA)-induced epileptiform activity of rats. With
      extracellular recording technique, the effects of SS on 114 units epileptiform
      discharge were investigated in penicillin (PEN)-treated 95 rat hippocampal
      slices. In response to the application of SS (10(-10), 10(-8), 10(-6) mol/L), the
      burst frequency of area CA1 62/105 (59.05%) recorded unit discharges was
      increased significantly, while that of 23/105 (21.9%) was decreased. These
      results suggest that SS in hippocampal CA1 subregion mainly precipitates
      epileptiform discharge. The addition of anti-somatostatin antibody (1 1000) to
      the perfusate partly blocked the epileptiform bursts triggered by PEN perfusion,
      while this antiepileptic effect of SSAB was reversed by application of SS (10(-8)
      mol/L). These indicate that endogenous SS may be involved in epileptiform
      discharge in area CA1 of hippocampus.

PMID- 11961583
TI  - [Effect of ischemia/reperfusion on the phosphorylation of synaptosomal tyrosine
      of hippocampus of Mongolian gerbils].
AB  - The effects of ischemia/reperfusion on the levels of protein tyrosine
      phosphorylation in the synaptosome of gerbil hippocampus and the effects of three
      drugs, ketamine (KT), a noncompetitive antagonist of NMDA receptor, nifedipine
      (ND), a voltage gated calcium channel (VGCC) antagonist and 6,7
      dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA receptor antagonist, on the
      phosphorylation were studied. The results showed that (1) 15 min of transient
      forebrain ischemia caused a marked decrease in the level of tyrosine
      phosphorylation of many protein bands, but, if followed by 15 min to 48 h of
      reperfusion, many protein bands including the 180 kD protein appeared to be
      increased; (2) the degree of tyrosine phosphorylation of the protein bands was
      higher than that of the sham-operated control, e.g. that of 180 kD protein was
      1.8 fold of control; (3) administration of KT and ND before ischemia attenuated
      the increase of 180 kD protein tyrosine phosphorylation, while DNQX had no
      effect; and (4) immunoprecipitation and Western blot confirmed that the NR2B
      subunits of the NMDA receptors were among the phosphorylated 180 kD protein and
      ischemia /reperfusion did not affect the level of protein expression of NR2B. The
      above results suggest that the increase of tyrosine phosphorylation of NR2B
      induced by ischemia/reperfusion may further activate NR channels and aggravate
      neuronal injury, and that NR channels and other protein can be regulated by
      tyrosine phosphorylation not only through NR channels themselves but also via L
      type VGCCs. Consequently, antagonists of both NR channels and L-type VGCCs may
      play a certain role in prevention and cure of ischemic brain injury.

PMID- 11961584
TI  - [Effects of hypoxia on the proliferation and differentiation of CD34(+)
      hematopoietic stem/progenitor cells and their response to cytokines].
AB  - To elucidate the effects of hypoxia on the proliferation and differentiation of
      CD34(+) hematopoietic stem/progenitor cells and their response to cytokines, the
      cells were isolated from umbilical cord blood by using a high-gradient magnetic
      cell sorting system (MACS). Mononuclear cells (MNC) and CD34(+) cells were
      incubated in severe hypoxia (1% oxygen) culture system, and the colony forming
      cells and antigen expression were studied by colony forming assays and FACS
      analysis. The results showed that incubation in severe hypoxia increased the
      number of erythroid bursts (BFU-E) (324.8+/-41.4/10(4) cells) generated from
      CD34(+) cells (191.2+/-34.5/10(4) cells in the control group, P<0.01). Severe
      hypoxia also enhanced the maintenance and cloning efficiency of BFU-E in a liquid
      culture system without growth factors, the number of BFU-E (152.4+/
      22.6/10(4)cells) was much bigger than that in the control group (74.2+/-9.3/10(4)
      cells, P<0.01). In cultures incubated in hypoxia, the percentage of CD34(+)
      cells was significantly higher (2.5+/-1.2-fold, P<0.05) than in those incubated
      in air. BFU-E cloning efficiency of MNC was not significantly affected by
      hypoxia. The above results show that hypoxia enhances the maintenance of
      erythroid progenitor cells generated from CD34(+) hematopoietic stem/progenitor
      cells, no matter growth factors are present or not. These positive effects of
      hypoxia did not occur for the other progenitors.

PMID- 11961585
TI  - [Changes in the iron uptake of bone marrow cells in exercised rats].
AB  - The changes in transferrin(Tf)-bound and non-Tf-bound iron uptake were observed
      in bone marrow cells from rats with exercise-induced low iron status. Female rats
      were randomly divided into an exercise group (EG) and a sedentary group (SG). At
      the end of a 6-month period, the bone marrow cells were freshly isolated. The Tf
      receptor number on the surface of erythroblasts was 890150+/-164849
      molecules/cell in SG and 2175360+/-462737 molecules/cell in EG (P<0.05). No
      significant difference in dissociation constant value was found between the two
      groups. The plateau of Tf internalization and the rates of cellular iron
      accumulation in EG were significantly higher than controls. Amounts of Tf-bound
      iron and Fe(II) uptake into cytosolic or stromal fractions were significantly
      higher in EG than those in cytosolic or stromal fractions of SG. With respect to
      the specific process of Fe(II), the michaelis constant value of iron uptake into
      the cytosol, rather than the stroma, in EG was significantly lower than that in
      SG; and the maximum rate of iron uptake into the stroma in EG was significantly
      higher than that in SG. The results show that exercise can increase Tf receptor
      mediated and carrier-mediated iron uptake in bone marrow cells. The increased Tf
      bound and Tf-free iron uptake may be helpful for heme synthesis.

PMID- 11961586
TI  - [A transient increase in CCK mRNA levels in amygdala following audiogenic
      seizures in audiogenic seizure-prone rats].
AB  - The effects of single and multiple seizures on cholecystokinin (CCK) mRNA levels
      in amygdala of audiogenic seizure-prone rats (P77PMC) were examined by in situ
      hybridization. The main results are as follows: (1) CCK mRNA positive neurons
      (No/0.01 mm(2)) in amygdala showed a transient increase in number from the 8+/-1
      to 58+/-5 (P<0.01) in 30 min and then returned to the control value in 2 h (9+/
      2, P>0.05), and (2) in the multiple consecutive seizure rats the increase in 30
      min (22+/-3) was less than that in the single seizure rats (P<0.01), and the
      number returned to normal in 1 h (6+/-1, P>0.05). These data indicate that the
      transient increase in CCK mRNA level in amygdala following single or multiple
      consecutive seizures of P77PMC may be involved in anti-convulsant mechanisms in
      response to acute seizures.

PMID- 11961587
TI  - [Determination of catecholamine secreted from rat adrenal medulla by in vivo
      voltammetry].
AB  - In vivo voltammetry using carbon fiber electrodes was employed to determine the
      catecholamine secreted from the adrenal medulla. The basal level of catecholamine
      in the medulla was between 0.1 and 0.5 micromol/L, but it increased markedly up
      to 5 30 micromol/L when the gland was made ischemic. The spontaneous release of
      catecholamine from the medulla was observed in both normal and ischemia
      conditions, but the frequency and amplitude of spontaneous release were increased
      significantly by ischemia. This implied that the animal was under serious stress
      condition. The above results also show that acetylcholine can induce the
      secretion of catecholamine in a dose-dependent manner.

PMID- 11961588
TI  - [Increased expression of c-fos in the brainstem nuclei involved in cardiova
      scular regulation by capsaicin].
AB  - Effects of intracarotid injected capsaicin on the expression of Fos proto
      oncogene in the brainstem nuclei involved in cardiovascular regulation were
      examined in 16 anesthetized rats with sinoaortic denervation. Only a few Fos-like
      protein immunoreactivity (FLI) neurons were found in the vehicle-control rats.
      Following intracarotid injection of capsaicin (10 micromol, 0.1 ml), the FLI
      neurons were markedly increased in nucleus paragigantocellularis lateralis (PGL),
      locus coeruleus (LC), area postrema (AP) and nucleus tractus solitarius (NTS), as
      compared with the results of vehicle-control rats, while the FLI neurons of raphe
      nuclei (RN) and periaqueductal gray (PAG) were not affected. The excitatory
      response to intracarotid injection of capsaicin was significantly inhibited by
      pretreatment with the vanilloid receptor (capsaicin receptor) antagonist
      ruthenium red (200 mmol, 0.1 ml). The results indicate that capsaicin may
      activate the neurons of the brainstem nuclei involved in cardiovascular
      regulation through vanilloid receptors, but does not exert any effects on PAG and
      RN.

PMID- 11961589
TI  - [Electrophysiological effects of calcitonin gene-related peptide on isolated
      sinoatrial node of the rabbit].
AB  - The purpose of this study was to investigate the electrophysiological effects of
      calcitonin gene-related peptide (CGRP) on the pacemaker cell of rabbit sinoatrial
      node (SAN) and to determine whether I(Ca) is involved in the effects. Action
      potentials (AP) were recorded from the isolated SAN with microelectrode
      technique. It was found: (1) CGRP (1 nmol/L) had no effect on AP configuration;
      CGRP (10 nmol/L) increased the maximal diastolic potential, AP amplitude and
      depolarization velocity of 0 and 4 phases, and decreased sinus cycle length and
      AP duration. After applying CGRP for 20 min the above effects reached to a
      maximum. (2) CGRP (100 nmol/L) caused arrhythmia in the SAN. (3) Calcium channel
      antagonists, CdCl2 and verapamil attenuated the electrophysiological changes in
      AP of SAN induced by CGRP (20 nmol/L). The results indicate that a calcium
      dependent mechanism may underlie the CGRP effects.

PMID- 11961590
TI  - GABAergic neurons in Kolliker-Fuse nucleus and Botzinger complex with axons
      projecting to phrenic nucleus.
AB  - Experiments were made on 6 adult cats. Brainstem neurons that project to the
      phrenic nucleus were retrogradely labeled by microinjection of WGA-HRP into
      phrenic nucleus. The brainstem sections were doubly processed for HRP
      histochemical staining with the TMB-Co-DAB method, and GABA immunohistochemical
      staining with anti-GABA primary antibody and FITC conjugated immunofluorescent
      secondary antibody. HRP-FITC double-labeled neurons were observed in the pontine
      Kolliker-Fuse nucleus and areas around the retrofacial nucleus (Botzinger
      complex). Double-labeled neurons were also observed in the raphe nucleus, the
      lateral paragigantocellular nucleus, and the vestibular nucleus. The results show
      that brainstem GABAergic neurons in these structures, especially those in the
      Kolliker-Fuse nucleus and the B?t.C, send axonal projections to the phrenic
      nucleus.

PMID- 11961591
TI  - [K(ATP) channel opener facilitates carotid sinus baroreflex in anesthetized
      rats].
AB  - The effects of cromakalim (Cro), a K(ATP) channel opener, on the carotid
      baroreflex were studied in 32 anesthetized rats with perfused isolated carotid
      sinus. The results obtained are as follows. (1) By perfusing the isolated carotid
      sinus with Cro (10 micromol/L), the functional curve of the baroreflex was
      shifted to the left and downward, with a peak slope (PS) increasing from 0.36+/
      0.01 to 0.48+/-0.01 kPa/kPa (P<0.001), whereas the reflex decrease in mean
      arterial pressure (RD) was increased from 5.78+/-0.14 to 7.87+/-0.12 kPa
      (P<0.001). Meanwhile, the threshold pressure (TP), equilibrium pressure (EP) and
      saturation pressure (SP) were all significantly decreased from 8.34+/-0.35 to
      6.41+/-0.09 kPa (P<0.01), 12.71+/-0.25 to 11.78+/-0.24 kPa (P<0.01) and 24.89+/
      0.25 to 22.56+/-0.16 kPa (P<0.001), respectively. Among the functional parameters
      of carotid baroreflex, the changes in RD, PS and TP induced by Cro were dose
      dependent. (2) By pretreatment with glibenclamide (10 micromol/L), a K(ATP)
      channel blocker, the above effects of Cro on the carotid baroreflex were
      abolished. (3) The Cro-induced change in the baroreflex was enhanced by
      preperfusing with adenosine (125 micromol/L). On the basis of the above results,
      it is concluded that Cro facilitates the carotid baroreflex, an effect
      attributable to the enhanced stretch of baroreceptors by dilation of sinus wall
      as a result of K(ATP) channel activation.

PMID- 11961592
TI  - [Effect of halothane on the muscarinic potassium current of the heart].
AB  - Acetylcholine (ACh) released from parasympathetic nerves binds to muscarinic (M2)
      ACh receptor (mAChR) in the heart, which leads to activation of muscarinic K(+)
      channel via the betagamma subunit of a G protein. The effect of a general
      anaesthetic (halothane) on the muscarinic K(+) channel (i(K,Ach)) in guinea-pig
      atrial cells was investigated using the whole-cell patch clamp technique.
      Halothane suppressed i(K,Ach), slowed down activation of i(K,Ach) and decreased
      peak i(K,Ach). When i(K,Ach) was activated by ACh acting via the muscarinic ACh
      receptors in the normal way, the decrease of i(K,Ach) was greater than the
      decrease when the muscarinic ACh receptor was bypassed and i(K,Ach) was activated
      by GTPgammaS. The above finding suggests that the suppression of i(K,Ach) by
      halothane is, in part, a result of the direct effect on the muscarinic K(+)
      channel or associated G protein. The decrease of i(K,Ach) by halothane may
      interfere with parasympathetic control of the heart.

PMID- 11961594
TI  - Minimally invasive surgery for thyroid and parathyroid diseases.
AB  - During the past 4 years, some minimally invasive procedures for thyroid and
      parathyroid surgery have been described. All these techniques have been
      demonstrated as feasible and safe. Nevertheless, the surgeon should be well
      trained to obtain the best results with these approaches. Moreover, not all
      patients are eligible for minimally invasive procedures. At the moment, they can
      be proposed for most patients with sporadic primary hyperparathyroidism, but only
      for a minority of patients with thyroid nodules. The results from minimally
      invasive procedures are almost comparable with those of conventional surgery, but
      they have additional advantages in terms of cosmetic result and postoperative
      pain. Therefore, these procedures should be considered a valid option by surgeons
      dealing with neck endocrine surgery.

PMID- 11961595
TI  - Laparoscopic abdominoperineal resection and anterior resection with curative
      intent for carcinoma of the rectum.
AB  - BACKGROUND: Within a 5-year period, 380 rectal carcinoma patients undergoing
      laparoscopic abdominoperineal excision or laparoscopic anterior resection were
      recruited to a multicenter study by 23 institutions in Germany and Austria. This
      study was initiated by the Laparoscopic Colorectal Surgery Study Group. RESULTS:
      One hundred forty-nine patients (39.2%) underwent abdominoperineal resection
      (APR), and 231 patients (60.8%) were treated by anterior resection (AR). The mean
      operating time was 208 min, and the conversion rate was 6.1%. Intraoperative
      complications, mostly vascular or bowel injuries, were observed in 22 patients
      (5.8%). Overall, a total of 257 postoperative complications and problems occurred
      in 143 patients, resulting in a morbidity rate of 37.6%. In the AR group, the
      anastomotic leakage rate increased as the distance of the tumor from the anal
      verge decreased. The perioperative mortality rate was low (6/1.6%). Most of the
      patients received a high transsection of the inferior mesenteric artery with
      radical lymph node dissection (342/90.0%); the mean number of recovered lymph
      nodes was 13.0, with considerable variation among the individual institutions.
      Intraoperative tumor cell spillage was reported in 12 patients (3.2%). Sufficient
      follow-up findings are available for 288 (77%) patients. To date, 19 patients
      have sustained a local recurrence (6.6%), and 30 (10.4%) have developed distant
      metastases. Within the (admittedly limited) mean follow-up of 24.8 months, the
      overall survival rate is 86.6%, the disease-free survival (freedom from both
      local recurrence and distant metastases) rate is 62.4% for APR, with the
      corresponding rates for AR being 71.7 and 54.8%, respectively, as established by
      the Kaplan-Meier function. These data show no alarmingly high recurrence rates at
      this time. CONCLUSION: In principle, laparoscopic anterior resection with
      curative intent generates considerably more reservations than laparoscopic
      abdominoperineal resection, which is technically much easier to perform.

PMID- 11961596
TI  - Early clinical results of endorectal surgery using a newly designed rectal tube
      with a side window.
AB  - BACKGROUND: Transanal endoscopic microsurgery (TEM) using the original Buess
      devices requires the use of a completely closed system for positive pressure gas
      insufflation. To simplify the setup of the system and expose the target lesion in
      the rectum without gas insufflation, we have developed a new operating rectal
      tube with a side window. METHODS: The new rectal tube is a transparent cylinder
      measuring 40 mm in diameter with its forward end closed and a 40-mm opening on
      its side. When a rectal tumor is captured within the opening, it can be clearly
      visualized without positive gas insufflation. Under endoscopic control, the
      lesion is then resected and the defect is closed by suturing. Using this new
      system, we performed endorectal surgery on 10 patients with rectal tumors. Our
      series included four benign adenomas, two carcinomas in situ, two T2 cancers, and
      two carcinoid tumors. RESULTS: The operation was performed successfully in all 10
      cases. There were no significant operative complications and the postoperative
      course was excellent in all cases. Pathological analysis revealed that the
      surgical margins of all specimens were completely free from tumor. CONCLUSIONS:
      Our early clinical results suggest that the newly designed operating rectal tube
      with a side window simplifies the endorectal surgical procedure and facilitates
      the safe resection of rectal tumors < 40 mm in diameter.

PMID- 11961597
TI  - Laparoscopic left colon resection for diverticular disease.
AB  - BACKGROUND: The aim of this study was to review our experience with laparoscopic
      sigmoid colectomy for diverticular disease. METHODS: All patients presenting with
      acute or chronic diverticulitis, obstruction, abscess, or fistula were included.
      Symptomatic diverticular disease was the main surgical indication (95%). RESULTS:
      Between March 1992 and August 1999 170 consecutive patients underwent surgery. Of
      these, 21 patients (12%) had significant obesity, with body mass index (BMI)
      greater than 30. The average length of surgery was 141 +/- 36 min. In 163
      patients (96%), the procedure was performed solely with the laparoscope. The
      nasogastric tube was removed on postoperative day 2 +/- 1.9, and oral feeding was
      started on postoperative day 3.4 +/- 2.1. The average length of hospital stay
      after surgery was 8.5 +/- 3.7 days. During the first postoperative month, there
      were no deaths. However, 11 patients (6.5%) had surgical complications: 5
      anastomotic leaks (2.9%), 1 intraabdominal abscess (0.6%), and 3 wound infections
      (1.7%). There were four reinterventions (2.4%), with two diverting colostomies.
      Secondarily, 10 anastomotic stenoses (5.9%) were observed. Eight patients
      required a reintervention: seven anastomotic resections by open laparotomy and
      one terminal colostomy. Seven patients (4.1%) reported retrograde ejaculation,
      and one reported impotence. CONCLUSIONS: The feasibility of the laparoscopic
      approach to diverticular disease is established with a conversion rate of 4%, a
      low incidence of acute septic complications (5.3%), and a mortality rate of 0%.
      Therefore, laparoscopic sigmoid colectomy has become our procedure of choice in
      the treatment of diverticular disease.

PMID- 11961598
TI  - Colonoscopy in mice.
AB  - INTRODUCTION: Current investigational models of murine colitis and colon cancer
      necessitate sacrifice of animals in order to obtain colonic tissue. The purpose
      of this study was to develop a safe method of murine colonoscopy that would allow
      serial evaluation and mucosal biopsies of the same animal. METHODS: Nine mice
      (two C3H, two C57/BL6, and five IL-10 deficient) were studied a total of four
      times each over 4 weeks. Three mice [APC (Min +/-)] were examined three times
      each. Mice were gavaged with 1 cc of a polyethylene glycol solution on the day
      prior to colonoscopy. Solid chow was withheld and the mice were maintained on
      Pedialyte. Mice were anesthetized with ketamine and xylazine. A flexible
      pediatric cystoscope (2.1-mm diameter) with a single biopsy channel was
      introduced per anum, and the colon was gently insufflated with air to a mean
      pressure of less than 5 mmHg. Saline irrigation was used when necessary. A single
      biopsy was obtained from the rectosigmoid colon during each examination. RESULTS:
      A total of 46 examinations were carried out. One mouse died after being
      anesthesized for the fourth examination, and two mice [one IL-10 knockout and one
      APC (Min+/-)] died one day after the 3rd examination. No other complications were
      noted. The average length of insertion was 3 cm. Transillumination allowed for
      localization of the endoscope tip. Biopsies, although quite small, were
      sufficient for pathologic evaluation and diagnosis. CONCLUSIONS: Murine
      colonoscopy is a safe and feasible technique. It permits consecutive visual and
      histopathological examinations, and it allows the investigator to monitor the
      response of the murine colon to experimental interventions.

PMID- 11961599
TI  - Laparoscopic antireflux surgery in the elderly.
AB  - BACKGROUND: Laparoscopic antireflux surgery is frequently denied to older
      patients with gastroesophageal reflux disease (GERD) because of a perceived
      higher operative complication rate, a decreased impact of the intervention on
      quality of life, and decreased cost effectiveness. This study compares disease
      severity, surgical outcomes, and impact on quality of life between elderly and
      young patients with GERD. METHODS: Patients were selected from a prospectively
      maintained database of 1100 patients who underwent various laparoscopic
      esophageal procedures at our institution. Only patients having chronic
      intractable GERD and a minimum 6 months' follow-up were included in the study.
      Thirty elderly patients with a mean age of 71.2 years (SD +/- 5.6) were compared
      with a group of 30 younger patients (mean age, 43.9 +/- 12.8 years). Comparisons
      were made between subjective and objective outcomes, operative results, and
      health-related quality of life (HQRL) scores using SF-36 instruments. RESULTS:
      The preoperative symptom assessment scores presenting frequency of symptoms on a
      0-4 scale), and preoperative pH and manometry data were comparable in the two
      groups. Elderly patients had significantly higher ASA (American Society of
      Anesthesiologists) scores. Each group demonstrated a significant improvement in
      the postoperative symptom assessment scores and the esophageal functional studies
      (p<0.05). However, no significant differences were found in terms of
      postoperative complications, postoperative hospital stay, postoperative symptom
      scores, Demeester scores, or the HRQL data. CONCLUSION: Laparoscopic antireflux
      surgery in elderly patients improves acid reflux and appears to be safe and
      effective as measured by postoperative testing in elderly and young patients.

PMID- 11961600
TI  - Training period in laparoscopic colorectal surgery.
AB  - BACKGROUND: Thorough training is essential to the success of colorectal
      laparoscopic surgery (LPS). The aim of this study was to evaluate the results of
      a 3-month training period in LPS. METHODS: Before beginning the study, the
      surgical team attended several courses of LPS and spent a long time working at a
      large animal facility to perfect laparoscopic techniques. Twenty-six consecutive
      patients underwent LPS in a 3-month training period. Controls (n = 26) who
      underwent open colorectal surgery (LPT) were selected to match the LPS patients
      for age, gender, primary disease, type of surgery, comorbidity, and nutritional
      status. RESULTS: Conversion to open surgery was necessary in one patient (3.8%).
      The operative time was 1 h longer for LPS than LPT (p < 0.001). The mean number
      of lymph nodes harvested was 17 in LPS and 18 in LPT (p = 0.76). The first flatus
      (p < 0.02) and bowel movement (p < 0.002) occurred earlier in the LPS group. The
      postoperative infection rate was 11.5% for LPS and 19.2% for LPT (p = 0.33). Two
      anastomotic leaks occurred in each group. The mean postoperative hospital stay
      was 9.6 days (standard deviation [SD], 2.6) for LPS and 11.0 days (SD, 5.2) for
      LPT (p = 0.68). Recovery of postoperative physical performance and social life
      occurred earlier in the LPS than the LPT group (p < 0.001). At 1-year follow-up,
      no difference was found in terms of cancer recurrence or long-term complications.
      CONCLUSION: Oncologic results and postoperative morbidity were comparable for LPS
      and LPT. LPS allows a faster postoperative recovery.

PMID- 11961601
TI  - Higher colon cancer tumor proliferative index and lower tumor cell death rate in
      mice undergoing laparotomy versus insufflation.
AB  - BACKGROUND: Our laboratory has previously shown that tumors are established more
      easily and grow larger after laparotomy than after laparoscopy. To characterize
      these differences in tumor growth further, the tumor cell death rates and tumor
      proliferation rates were compared in vivo after full sham laparotomy versus
      carbon dioxide (CO2) insufflation. METHODS: Female Balb/C mice (n = 36) were
      inoculated intradermally in the dorsal skin with 106 C-26 colon adenocarcinoma
      cells in 0.1 ml of culture media no more than 1 h before interventions. The mice
      then were randomized to one of three groups: anesthesia control, CO2
      insufflation, or sham laparotomy. The anesthesia control group underwent no
      procedure. The insufflation group underwent CO2 pneumoperitoneum (4-6 mmHg) for
      20 min via a 20-gauge angiocatheter. The laparotomy group underwent a midline
      incision from xiphoid to pubis, which was closed after 20 min. Tumors were
      excised from half the mice in each group on postoperative day 7, and from the
      remaining mice on postoperative day 14. Sections of tumors were made then stained
      separately for free 3? hydroxyl ends of genomic deoxyribonucleic acid (DNA) using
      fluorescein-deoxyunidine triphosphate (dUTP), and immunohistochemically for
      proliferating cell nuclear antigen (PCNA). Apoptosis was measured by quantitating
      DNA strand breaks in individual cells using fluorescence microscopy. Fluorescein
      positive cells in five random high-power fields (x200) were counted in a blinded
      fashion. The proliferative index of each tumor was determined by averaging PCNA
      positive cells in five high-power fields (x450) counted in a blinded fashion with
      the aid of an optical grid. RESULTS: On postoperative day 7, there was no
      significant difference in the proliferative index or apoptotic rates among the
      three groups. On postoperative day 14, the proliferative index in the laparotomy
      group was significantly higher than in either the insufflation or control group
      (p < 0.001). The proliferative index in the insufflation group also was
      significantly higher than in the control group (p < 0.05). Inverse differences in
      apoptotic rates were found. The apoptotic rate in the laparotomy group was
      significantly lower than in either the insufflation (p < 0.05) or control group
      (p < 0.001). The apoptotic rate in the insufflation group was significantly lower
      than in the control group (p < 0.001). CONCLUSIONS: We have demonstrated that
      there is a significantly higher rate of tumor cell proliferation and a
      significantly lower rate of tumor cell death with the C-26 colon adenocarcinoma
      tumor line after laparotomy than after insufflation or anesthesia alone on post
      operative day 14. The mechanisms of these phenomena are unclear. It appears that
      certain factors postoperatively stimulate tumors to proliferate at a higher rate,
      causing tumor cells to die at a lower rate in the laparotomy group than in the
      insufflation group.

PMID- 11961602
TI  - Safety and long-term outcome of laparoscopic antireflux surgery in patients in
      their eighties and older.
AB  - BACKGROUND: The elderly have more severe reflux disease and paraesophageal
      hernias than younger patients, leading to a high failure rate of medical therapy.
      Laparoscopic antireflux surgery has an overall mortality of 0.1% and a low
      morbidity, making it a safe and beneficial procedure for the elderly. METHODS: We
      performed a retrospective study of octo- and nonogenerians with a mean follow-up
      of 3.1 years after laparoscopic fundoplication. Thirty (3.5%) patients who were
      in their eighties or older are reported. Preoperative symptoms, esophageal
      testing, postoperative symptoms, and satisfaction rate were analyzed. RESULTS:
      Fifty-seven percent of patients had paraesophageal hernias. Mean duration of
      procedures was 146 +/- 49 min, blood loss was 76 +/- 101 ml, and hospitalization
      was 2.2 +/- 1.0 days. There was one conversion to laparotomy, two intraoperative
      complications, and no deaths. Follow-up data were available in 93% of patients.
      Mean follow-up time was 3.1 years. Two died of unrelated causes. At follow-up 96%
      stated that their surgical outcome was satisfactory. Two patients were suffering
      from severe symptoms. Overall well-being at follow-up was 7.5 (range 3-10) on a
      10-point scale in comparison to 2.2 (range 1-5) before surgery (p = 0.03).
      CONCLUSION: Laparoscopic surgery is a good option for the treatment of severe
      gastroesophageal reflux disease in octo- and nonagenarians.

PMID- 11961603
TI  - Risk factors for complications of laparoscopic Nissen fundoplication.
AB  - BACKGROUND: Although the rate of complications from laparoscopic Nissen
      fundoplication is low and the adverse postoperative sequelae are well known, both
      are disturbing for the patient. Identifying risk factors could be helpful in the
      better selection of patients for this procedure. METHODS: A retrospective review
      of 126 patients with a mean follow-up period of 3.5 years was conducted. The
      patients' demographics, pre- and postoperative symptoms, and outcomes were
      analyzed and compared. RESULTS: Three groups of patients were distinguished:
      (group 1) 9 patients with intraoperative complications (5 with perforation, 3
      with hemorrhage, 1 with pneumothorax); (group 2) 16 patients with postoperative
      complications (5 with severe dysphagia, 4 with failure, 2 with pneumonia, 2 with
      incisional hernia, 1 with intestine perforation, 1 with fundoplication
      herniation, 1 with infection, 1 with gastric ulcer); and (group 3) 101 patients
      without any complications. The patients'demographics, preoperative symptoms, and
      preoperative studies were comparable in all three groups. The body mass index
      (BMI) was significantly higher (p < 0.05) statistically in group 1 (32.4 kg/m2)
      and group 2 (33.6 kg/m2) than in group 3 (28.7 kg/m2). However, the Visick grade
      and the subjective outcome were similarly good in all three groups. CONCLUSIONS:
      Although preoperative studies and symptoms do not seem to predict complications
      of laparoscopic Nissen fundoplication, patients with an increased BMI were at
      increased risk for complications in this study. Therefore, such patients should
      be counseled appropriately regarding the greater likelihood of intraoperative and
      postoperative complications.

PMID- 11961604
TI  - Laparoscopic fundoplication.
AB  - BACKGROUND: The effectiveness of laparoscopic Nissen fundoplication (LNF) was
      assessed in patients with chronic gastroesophageal reflux disease (GERD) using pH
      study and different quality-of-life indexes. We correlated both types of data and
      hypothesised that improvement in quality of life following LNF does not
      necessarily correlate with improvement in pH values. METHODS: Seventy patients
      presenting with typical symptoms of GERD (14 with Barrett's esophagus) underwent
      LNF between May 1997 and December 2000. All patients were evaluated both prior to
      and 3 months after surgery using 24-h pH study, endoscopy, and a validated
      quality-of-life questionnaire. RESULTS: Following LNF, reflux was reduced to
      normal in all but six patients. Howevers despite persistent reflux, the
      Gastrointestinal Quality of Life Index (GQLI), of these six patients improved
      postoperatively from 79.5 +/- 12.2 to 111.7 +/- 8.3. These results correlate with
      those of patients who had normal postoperative pH studies-namely, 88.5 +/- 19.3
      to 112 +/- 16.7. There was no difference in quality-of-life improvement between
      patients with Barrett's esophagus and those without it. CONCLUSION: There is only
      a weak correlation between quality-of-life assessment and pH study. Because the
      patient's quality of life is likely to improve following LNF, an objective means
      parameter of assessing the effectiveness of antireflux surgery, such as pH study
      or endoscopy, is recommended.

PMID- 11961606
TI  - Selection criteria among gastroenterologists and surgeons for laparoscopic
      antireflux surgery.
AB  - BACKGROUND: Symptomatic gastroesophageal reflux disease (GERD) affects a
      substantial proportion of the American population. The diagnosis and treatment of
      GERD has advanced tremendously over the past 30 years. However, there remains a
      lack of understanding about the differences and advantages that laparoscopic
      antireflux surgery offers and a lack of agreement on the ideal surgical
      candidate. The purpose of this study was to determine whether a significant
      difference exists in the practice habits and selection criteria for surgery
      between gastroenterologists and laparoscopic surgeons. METHODS: Surveys were sent
      to 1,000 randomly selected members of the American Gastroenterological
      Association (AGA) and to 1,000 randomly selected members of the Society of
      American Gastrointestinal Endoscopic Surgeons (SAGES). As a result, 20% of the
      AGA surveys and 33% of the SAGES surveys were completed and returned. RESULTS:
      The AGA group considered patients whose symptoms are not well controlled, those
      who have complications of disease, and those who require significant lifestyle
      changes to control their symptoms as the best candidates for surgical evaluation.
      As a group, gastroenterologists remain somewhat hesitant to refer patients for
      laparoscopic antireflux surgery. Surgeons considered patients whose symptoms have
      been well controlled with medical therapy, those who have complications of
      disease, and those who require significant lifestyle changes to control their
      symptoms as ideal candidates for fundoplication. CONCLUSION: A consensus should
      be reached between surgeons and gastroenterologists in establishing criteria for
      surgical intervention to manage GERD.

PMID- 11961605
TI  - Laparoscopic versus open fundoplication in infants.
AB  - BACKGROUND: Laparoscopic esophagogastric fundoplication is an effective treatment
      for severe gastroesophageal reflux disease (GERD), although its role in the very
      young is still largely undetermined. We review our surgical outcome in infants
      with severe GERD, comparing laparoscopic (LNF) with open (ONF) Nissen
      fundoplication. METHODS: This study reviewed 55 consecutive Nissen
      fundoplications performed for GERD on infants less than 1 year old at our
      institution between January 1996 and June 2000. The follow-up period for LNF
      averaged 14.2 months (range, 3.3-42 months), as compared with 16.5 months (range,
      1-37.1 months) for ONF (p was not significant, t-test). Surgical outcome was
      compared in terms of the following parameters: average operative time, times to
      initiation and completion of feeding schedule, postoperative complications, and
      recurrence rates. RESULTS: For the study, 53 infants were divided into two
      groups: LNF (n = 39; 73.6%) and ONF (n = 14; 26.4%). The average operating time
      for LNF was 120 +/- 24 min (range, 60-195 min), as compared with 91 +/- 21 min
      (range, 60-135 min) for ONF (p < 0.05, t-test). Time to initiation of
      postoperative feeding schedule was 1.3 +/- 0.3 days for LNF, as compared with 3
      +/- 0.9 days for ONF (p < 0.05, t-test). Full feedings were reached in 1.7 +/-
      0.6 days for LNF, as compared with 1.3 +/- 0.9 for ONF (p was not significant, t
      test). During the short-term follow-up period, recurrent reflux developed in 2/14
      ONF patients (14.3%) as compared with 1/39 LNF patients (2.6%) (p < 0.05).
      CONCLUSIONS: We conclude that in addition to sparing infants the morbidity of
      celiotomy, laparoscopic Nissen fundoplication had a surgical outcome comparable
      to that of traditional open fundoplication in infants with severe GERD.
      Importantly, resumption of goal nutritional regimens was equally efficient in
      both groups.

PMID- 11961607
TI  - Immediate radiographic assessment following laparoscopic antireflux operations is
      unnecessary.
AB  - BACKGROUND: Laparoscopic antireflux operations (LAP) have become increasingly
      common for the treatment of gastroesophageal reflux disease (GERD). We sought to
      determine if routine postoperative barium contrast studies following LAP were
      clinically efficacious in identifying technical problems and life-threatening
      complications related to the surgical intervention. METHODS: From January 1996 to
      December 1997, 112 barium studies were performed following 112 LAP procedures (47
      male/65 female patients; mean age, 51 years) (group I). This group was compared
      to a subsequent cohort of 67 patients who underwent LAP between January 1998 and
      July 1998 without routine early postoperative barium contrast study (group II).
      RESULTS: In 111/112 of the barium studies of group I, no radiographic abnormality
      was identified. The average length of stay (LOS) for these patients was 2.6 days.
      Routine barium studies were not utilized in group II. The average length of stay
      for patients in group II was 1.4 days. Twelve group II patients underwent early
      postoperative barium studies to evaluate suspicious clinical symptoms. None of
      these 12 postoperative studies identified important problems, nor did they alter
      the patients' clinical management. However, because of the barium study, their
      LOS was equivalent to those patients who had undergone routine barium study (2.4
      days). There was an increase of $1451.80 in hospital charges in the group of
      patients who had a barium study, largely as a result of the increased LOS.
      CONCLUSION: The routine use of these studies results in increased patient charges
      and a prolongation in the length of hospital stay. Immediate postoperative barium
      studies following laparoscopic antireflux operations are of little value in
      determining important postoperative problems among patients undergoing LAO.

PMID- 11961608
TI  - A canine model of gastroesophageal reflux disease (GERD).
AB  - BACKGROUND: Although a variety of antireflux procedures and medications are used
      to treat gastroesophageal reflux disease (GERD), reliable large-animal models of
      GERD that can be used to objectively compare the efficacy of these treatments are
      lacking. METHODS: Esophageal manometry and 24-h gastroesophageal pH monitoring
      with event data were performed in 18 mongrel dogs with a cervical esophagopexy.
      We then calculated a modified DeMeester score: The Duke Canine reflux score
      (DCR). Thereafter, the animals underwent a 4-cm anterior distal esophageal
      myotomy, incision of the left diaphragmatic crus, and intrathoracic gastric
      cardiopexy. Postoperative 24-h pH and manometry were obtained 2 weeks later.
      RESULTS: The postoperative 24-h pH results showed a significant increase in the
      mean DCR score (5.9 +/- 4.5 vs 84.9 +/- 56.1, p < 0.0002), and manometry
      indicated a significant decrease in mean lower esophageal sphincter (LES)
      pressure (7.1 +/- 2.9 vs 3.2 +/- 2.5 mmHg, p < 0.0001). CONCLUSION: This
      technique reliably creates a canine model of GERD.

PMID- 11961609
TI  - Laparoscopic myotomy vs endoscopic dilation in the treatment of achalasia.
AB  - BACKGROUND: The aim of this study was to compare the results obtained in 14
      patients with achalasia who underwent laparoscopic Heller's myotomy and Dor's
      fundoplication with those of 16 patients who had endoscopic dilation. METHODS:
      The diagnosis of achalasia was confirmed by manometry, endoscopy, and barium
      swallow. Esophageal symptoms were quantified before and after treatment using a
      clinical scale. Six patients had had endoscopic dilation prior to surgery.
      RESULTS: Before treatment, the patients in the surgical group complained of more
      severe dysphagia (median, 5; range, 0-5 vs median 4; range, 3-5) and chest pain
      (median, 3; range, 0-5 vs median, 1.5; range, 0-5), but both groups were
      comparable with respect to regurgitation, heartburn, and manometric results. Both
      groups achieved significant clinical improvement. The severity score decreased
      from 5 (range, 0-5) to 1 (range, 0-3) (p < 0.05) for dysphagia to solids in the
      laparoscopic group and from 4 (range, 3-5) to 1 (range, 0-5) (p < 0.05) in the
      endoscopic group. Lower esophageal sphincter (LES) basal pressure decreased
      significantly in both groups (from 29.3 to 11.8 mmHg in the laparoscopic group
      and from 28.9 to 16.5 mmHg in the endoscopic group). After treatment, there were
      no significant clinical differences between the two groups. Two patients in the
      surgical group were converted to open surgery. CONCLUSION: Laparoscopic myotomy
      is as save and effective as endoscopic dilation in the treatment of achalasia.

PMID- 11961610
TI  - Cardiac function during laparoscopic vs open gastric bypass.
AB  - BACKGROUND: Hypercarbia and increased intraabdominal pressure during prolonged
      pneumoperitoneum can adversely affect cardiac function. This study compared the
      intraoperative hemodynamics of morbidly obese patients during laparoscopic and
      open gastric bypass (GBP). METHODS: Fifty-one patients with a body mass index
      (BMI) of 40-60 kg/m2 were randomly allocated to undergo laparoscopic (n = 25) or
      open (n = 26) GBP. Cardiac output (CO), mean pulmonary artery pressure (MPAP),
      pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), heart rate
      (HR), and mean arterial pressure (MAP) were recorded at baseline,
      intraoperatively at 30-min intervals, and in the recovery room. Systemic vascular
      resistance (SVR) and stroke volume (SV) were also calculated. RESULTS: The two
      groups were similar in terms of age, weight, and BMI. Operative time was longer
      in the laparoscopic than in the open group (p < 0.05). The HR and MAP increased
      significantly from baseline intraoperatively, but there was no significant
      difference between the two groups. In the laparoscopic group, CO was unchanged
      after insufflation, but it increased by 5.3% at 2.5 h compared to baseline and by
      43% compared to baseline in the recovery room. In contrast, during open GBP, CO
      increased significantly by 25% after surgical incision and remained elevated
      throughout the operation. CO was higher during open GBP than during laparoscopic
      GBP at 0.5 h and at 1 h after surgical incision (p < 0.05). During laparoscopic
      GBP, CVP, MPAP, and SVR increased transiently and PAWP remained unchanged. During
      open GBP, CVP, MPAP, and PAWP decreased transiently and SVR remained unchanged.
      There was no significant difference in the amount of intraoperative fluid
      administered during laparoscopic (5.5 +/- 1.6 L) and open (5.6 +/- 1.7 L) GBP.
      CONCLUSION: Prolonged pneumoperitoneum during laparoscopic gastric bypass does
      not impair cardiac function and is well tolerated by morbidly obese patients.

PMID- 11961611
TI  - Does pneumatic dilatation affect the outcome of laparoscopic cardiomyotomy?
AB  - BACKGROUND: Controversy surrounds the choice of laparoscopic cardiomyotomy as the
      primary treatment for achalasia or a second-line treatment following the failure
      of nonsurgical treatment. Laparoscopic cardiomyotomy can be more difficult
      technically following pneumatic dilatations. The aim of this study was to compare
      the outcome obtained with primary laparoscopic cardiomyotomy to that achieved
      when the procedure is performed following failed pneumatic dilatation. METHODS:
      Laparoscopic cardiomyotomy was performed in seven patients following a median of
      four pneumatic dilatations (group A) and in five patients as their primary
      treatment (group B). Outcome was measured using manometry, a modified DeMeester
      symptom scoring system, and a quality-of-life questionnaire. RESULTS: There were
      no significant differences between groups A and B in sex, age, preoperative
      modified DeMeester score, or mean barrier pressure. Six of seven group A patients
      had evidence of periesophageal and submucosal fibrosis at surgery, but this
      condition was not seen in group B patients. The operative time was slightly
      longer in group A patients. There was no difference in complication rates (one
      primary hemorrhage in group A and one esophageal perforation in group B), and
      both groups had a significantly improved modified DeMeester score at 6 weeks and
      at long-term follow-up (median, 26 months). Eleven of 12 patients said that they
      would choose laparoscopic cardiomyotomy as their primary treatment if newly
      diagnosed with achalasia. CONCLUSIONS: Laparoscopic cardiomyotomy is safe and
      effective as a primary or second-line treatment following pneumatic dilatations
      in patients with achalasia.

PMID- 11961612
TI  - Endoscopic thyroid resection using cutaneous elevation in lieu of insufflation.
AB  - BACKGROUND: Laparoscopic surgery to resect cervical masses has gained increasing
      acceptance during the past decade. This report describes the authors' technique
      and experience using total video endoscopic surgery to resect thyroid masses.
      METHODS: The video camera is introduced through a 12-mm trocar inserted via a 10
      mm infraclavicular incision in the sternal line. This incision will be hidden by
      the patient's undergarments postoperatively. An incision for a 12-mm trocar is
      made in each axilla, with additional incisions in the anterior chest made as
      necessary for the endoscope and instruments. Excellent exposure is produced by
      elevating the skin with hooks rather than by using carbon dioxide insufflation.
      This method reduces the incidence of subcutaneous emphysema and
      pneumomediastinum. RESULTS: Twenty-two thyroid lesions were resected using total
      video endoscopic surgery (adenoma, 13; cancer, 5; benign cyst, 3; and Graves'
      disease, 1). Procedures included thyroidectomy (12), thyroidectomy and
      isthmusectomy (4), and subtotal thyroidectomy (2). Subtotal cervical adenectomy
      was performed in 3 patients with papillary carcinoma. Cosmetic results were
      excellent. CONCLUSION: Endoscopic surgery of the neck is safe, minimally
      invasive, and produces excellent cosmetic results. However, it is in an early
      stage of development. Techniques have yet to be standardized, and specialized
      instruments are not available. The field is likely to mature as surgeons gain
      more experience.

PMID- 11961613
TI  - Endoscopic thyroidectomy and parathyroidectomy by the axillary approach. A
      preliminary report.
AB  - BACKGROUND: The use of endoscopic procedures leads to a reduction in the size of
      the surgical scar, making it more inconspicuous. In this paper, we evaluated the
      merits and limits of endoscopic neck surgery. METHODS: Between August 1999 and
      July 2000, 102 patients underwent neck surgery in our department for thyroid or
      parathyroid disease. Twenty-eight of them were treated by the axillary. A 12-mm
      and two 5-mm trocars were inserted through the skin of the axilla. Carbon dioxide
      was then insufflated up to 4 mmHg, and the endoscopic surgery was performed.
      RESULTS: Endoscopic procedures were performed successfully in 26 cases (19
      thyroidectomies and seven parathyroidectomies). There were two conversions to
      open procedures. The mean operating times for the thyroidectomies and
      parathyroidectomies were 212 and 171 min, respectively. No evidence of injury to
      the recurrent laryngeal nerve was observed in any of the cases. The postoperative
      cosmetic status of the patients was excellent. CONCLUSION: We believe that
      endoscopic thyroidectomy and parathyroidectomy by the axillary approach will find
      a role in the treatment of endocrine diseases in the neck.

PMID- 11961614
TI  - Anterior, lateral, and posterior retroperitoneal approaches in endoscopic
      adrenalectomy.
AB  - BACKGROUND: Three approaches are currently used for endoscopic adrenalectomy-the
      lateral (transperitoneal), the posterior (retroperitoneal), and the anterior
      (transperitoneal). Both the lateral and posterior approaches are performed with
      the patient placed in the flank decubitus position; in the anterior approach the
      patient is supine. This study was designed to compare these three types of access
      in a relatively large series of patients undergoing adrenalectomy at three
      different institutions. METHODS: Laparoscopic adrenalectomy was performed in 216
      patients with a variety of adrenal disorders, including 66 patients with Conn's
      syndrome, 55 with incidentaloma, 58 with Cushing's syndrome, 33 with
      pheochromocytoma, two with virilizing adrenogenital syndrome, and two with other
      lesions. Seventy-two adrenalectomies were performed using the lateral access, 67
      via the posterior approach, and 77 via the transperitoneal anterior approach.
      There were 111 right and 105 left lesions. RESULTS: One patient in the lateral
      access group and three patients in the posterior group required conversion to
      open surgery. No conversions were needed in the anterior group. The learning
      curve was statistically significant only in the anterior access group. In both of
      the transperitoneal approaches (lateral and anterior), a statistically
      significant correlation was found between the operative time and the patient's
      body mass index (BMI). The postoperative hospital stay and time needed to return
      to normal activities were similar for the three groups. One patient who underwent
      retroperitoneal adrenalectomy for Cushing' disease died in the postoperative
      period of Candida sepsis and peritonitis. CONCLUSIONS: The anterior access route
      requires that the surgeon be skilled in advanced laparoscopic surgery. Both of
      the transperitoneal approaches (anterior and lateral) are suitable to remove
      larger adrenal masses. The posterior access may represent a better option in
      obese patients or in cases with small lesions.

PMID- 11961615
TI  - Laparoscopic adrenalectomy for pheochromocytoma.
AB  - BACKGROUND: Laparoscopic adrenalectomy for Conn's syndrome, Cushing's disease,
      cortisol-producing adenomas, and nonfunctioning adenomas has been well
      established. This study was intended to evaluate the clinical outcomes of
      patients undergoing laparoscopic adrenalectomy for pheochromocytoma, and to
      assess the efficacy and safety of a minimally invasive approach. METHODS: Data
      were collected prospectively on all patients undergoing laparoscopic
      adrenalectomy for pheochromocytoma over a 5-year period. RESULTS: In this study,
      39 consecutive patients underwent laparoscopic resection of a pheochromocytoma:
      38 adrenal (23 left, 15 right) and 1 extraadrenal paraganglioma. There were no
      conversions to open surgery. The mean tumor size was 5.2 cm (range, 2-12.1 cm).
      Average operative time was 159 min (range, 100-265 min), and average estimated
      blood loss was 72 ml (range, 30-350 ml). Intraoperative hypertension (systolic
      blood pressure > 170 mmHg) occurred in 67% of the patients, and hypotension
      (systolic blood pressure < 90 mmHg) in 39% of the patients. The mean length of
      stay was 2.1 days (range, 1-4 days). There were three minor postoperative
      complications. During a mean follow-up period of 14 months, there were no
      mortalities or recurrences of endocrinopathy. CONCLUSIONS: Laparoscopic resection
      of pheochromocytomas can be accomplished safely despite frequent episodes of
      hemodynamic variability equal to those of historic open control subjects. A short
      hospital stay with expedient recovery,minimal wound complications, and lack of
      endocrinopathy recurrence makes a minimally invasive approach the procedure of
      choice for the management of pheochromoctyoma.

PMID- 11961616
TI  - The impact of splenic weight on laparoscopic splenectomy for splenomegaly.
AB  - BACKGROUND: Enlarged spleens increase the technical difficulties associated with
      laparoscopic splenectomy (LS). The aim of this study was to analyze the impact of
      splenic weight on the results of LS. METHODS: We performed a prospective analysis
      of 20 LS for splenomegaly and 40 LS for normal spleen in terms of intraoperative
      and early postoperative outcome. RESULTS: Patients with splenomegaly had longer
      operative times and higher conversion and transfusion rates than those with
      normal spleens. Patients with spleens weighing < 2000 G experienced less blood
      loss, fewer conversions, and a shorter postoperative hospital stay than those
      with spleens > 2000 g. No differences-except for the longer operative time-were
      observed between normal-sized spleens and those weighing < 2000 G. CONCLUSIONS:
      LS for splenomegaly is feasible for experienced laparoscopic surgeons. For
      spleens weighing < 2000 G, the outcome was comparable to that of normal spleens,
      whereas LS for spleens >2000 g was associated with a higher conversion rate,
      greater blood loss, a longer hospital stay, and increased morbidity.

PMID- 11961618
TI  - Impact of upper endoscopic survey during percutaneous endoscopic gastrostomy tube
      placement.
AB  - BACKGROUND: No consensus exists concerning the utility of a full diagnostic upper
      endoscopy during percutaneous endoscopic gastrostomy (PEG) tube placement. We
      evaluate the effect of a complete survey on identifying and treating unsuspected
      gastrointestinal pathology. METHODS: During a 10-year period (1990-2000), 1,706
      patients underwent attempted PEG tube placement by five different surgical
      endoscopists at one institution. A complete survey of the esophagus, stomach, and
      proximal duodenum was attempted in all cases. Endoscopic findings and
      recommendations were recorded in a computerized log and patient charts. Pathology
      results were obtained from a computerized pathology database and patient charts.
      RESULTS: Placement of a PEG tube was successful in 97%, and a full survey was
      possible in 99% of the cases. Pathologic findings were found in 38% of the
      surveyed patients (esophagus, 7%; stomach, 24%; duodenum, 7%). One group with
      gastrointestinal polyps or gastric ulcers (5.7%) was identified as possible
      candidates for endoscopic intervention. In 30% of this group (1.8% of the total)
      a biopsy was performed, or bleeding was treated endoscopically. In a second group
      pathology was identified in the duodenum (6.4%) that would not have been
      recognized without a full survey. These duodenal findings resulted in a
      recommendation for treatment change in 38% of this group (2.4% of the total).
      CONCLUSIONS: Upper endoscopic survey before PEG tube placement showed a
      significant amount of unsuspected gastrointestinal pathology. Findings requiring
      biopsy, immediate treatment, or a change in medical treatment occurred in 4.2% of
      the cases, and these findings did not prevent PEG tube placement in any patient.

PMID- 11961617
TI  - Laparoscopic adrenal-sparing surgery for primary hyperaldosteronism due to
      aldosterone-producing adenoma.
AB  - BACKGROUND: Laparoscopic adrenalectomy has been shown to be safe and effective in
      the treatment of patients with primary hyperaldosteronism due to aldosterone
      producing adenoma. Most laparoscopic adrenalectomies for aldosterone-producing
      adenomas involve total removal of the adrenal gland, and there have been few
      reports of laparoscopic adrenal-sparing surgery or partial adrenalectomies.
      METHODS: A prospective review is performed on eight patients with primary
      hyperaldosteronism due to aldosterone-producing adenoma who underwent
      laparoscopic transperitoneal adrenal-sparing surgery in our institution over a 2
      year period. RESULTS: There were 1 male and 7 females with a mean age of 43.1
      years. The mean diameter of the adenoma was 2 cm; there were six right-sided
      lesions and two left-sided lesions. The adenoma was located in the anterior
      margin of the adrenal gland in seven cases and was removed by laparoscopic
      enucleation. One patient had a partial adrenalectomy using the vascular stapler
      for an adenoma that was located posteriorly in the adrenal gland. Hemostasis was
      excellent in all cases. All patients were able to tolerate liquid orally on the
      day of operation and were on diet on the second postoperative day. Postoperative
      analgesic requirement was minimal. The mean hospital stay was 3.8 days. At a mean
      follow-up of 25 months, seven patients were cured of their hypertension and one
      patient had her antihypertensive medications significantly reduced. CONCLUSION:
      Laparoscopic transperitoneal adrenal-sparing surgery is safe and effective in the
      treatment of patients with primary hyperaldosteronism due to aldosterone
      producing adenoma.

PMID- 11961619
TI  - Enteroscopic treatment of early postoperative small bowel obstruction.
AB  - BACKGROUND: Early postoperative small bowel obstruction (EPSBO) occurs in 1% of
      patients undergoing laparotomy and has a mortality rate exceeding 17%.
      Nasogastric (NG) decompression is successful in avoiding reoperation in 73% of
      patients. Repeat laparotomy has been recommended when obstruction does not
      resolve after 14 days of NG decompression. We report four patients with EPSBO
      treated successfully with push enteroscopy after failed NG decompression.
      METHODS: Four patients who failed NG decompression underwent push enteroscopy
      instead of repeat laparotomy. EPSBO was diagnosed if obstruction lasting more
      than 14 days developed after initial resolution of postoperative ileus, high NG
      output persisted postoperatively for 21 days in the absence of sepsis, or
      radiographic signs of obstruction persisted. Small bowel series or computed
      tomography were utilized when radiographic assessment was necessary. The Olympus
      SIF 100 push enteroscope was introduced with an overtube using topical anesthesia
      and intravenous sedation. After maximal insertion, the enteroscope was withdrawn
      without evacuation of insufflated air. NG tubes were placed after enteroscopy and
      patients were followed clinically. Flatus, defecation, and tolerance of a general
      diet defined resolution of EPSBO. RESULTS: EPSBO resolved 24 to 36 h following
      enteroscopy, and all patients were discharged on general diets 48 h after return
      of bowel function. Readmission has not been necessary during 18- to 30-month
      follow-up. CONCLUSIONS: Our experience suggests that push enteroscopy is
      successful in treating EPSBO and should be considered prior to reoperation. Push
      enteroscopy may eliminate the hazards of repeat laparotomy and reduce the
      morbidity, treatment cost, and lengthy hospital stays associated with this
      uncommon surgical complication.

PMID- 11961620
TI  - Bidirectional endoscopy in patients with fecal occult blood.
AB  - BACKGROUND: Current screening protocols for colorectal cancer depend primarily on
      fecal occult blood testing (FOBT). However, positive test results do not always
      indicate the presence of a colonic neoplasm. METHODS: We reviewed the results of
      100 consecutive bidirectional (upper and lower) endoscopic procedures performed
      to evaluate positive FOBT results. Patients were excluded if they presented with
      gross bleeding, a history of bowel lesions, or previous intestinal operations.
      There were 31 women and 69 men whose mean age was 51 years. RESULTS: Major
      abnormalities were found on esophagogastroduodenoscopy (n = 24), colonoscopy (n =
      13), or both studies (n = 2). Active bleeding was manifested in two patients,
      (Barrett's ulcer, duodenal arteriovenous malformation). Two other patients had
      malignancy: One had a cecal adenocarcinoma and the other a gastric
      adenocarcinoma. Various benign lesions also were identified in the stomach
      including esophagitis (n = 8), ulcers/erosions (n = 8) varices (n = 5), and
      arteriovenous malformations (n = 2). Colonic pathology included polyps (n = 8),
      arteriovenous malformations (n = 3), and rectal varices (n = 1). Diverticulosis
      and hemorrhoidal disease were present in 29 and 16 patients, respectively, but
      were not considered to be likely sources of a positive FOBT. CONCLUSION: Positive
      FOBT results may indicate the presence of either upper or lower intestinal
      pathology, and bidirectional endoscopy is an efficient and accurate technique for
      the comprehensive evaluation of occult bleeding.

PMID- 11961621
TI  - Prospective randomized comparison of laparoscopic-assisted vaginal hysterectomy
      (LAVH) with abdominal hysterectomy (AH) for the treatment of the uterus weighing
      >200 g.
AB  - BACKGROUND: Laparoscopic-assisted vaginal hysterectomy (LAVH) can be used for the
      vaginal removal of large uteri (200 g), which are conventionally treated with an
      abdominal approach (AH). METHODS: Forty-eight women with a sonographically
      estimated uterine weight of >200 g were prospectively randomized to undergo
      either LAVH (n = 28) or AH (n = 20). RESULTS: The median uterus weight was 334 g
      for LAVH vs 428 g for AH (not significant). The median operative time (133 vs 132
      min) and duration of recuperation (42 vs 42 days) were similar. LAVH was
      associated with significantly less intraoperative blood loss (median, 200 vs 600
      ml; p < 0.05), a lower pain index at postoperative day 4 (median [who scale], 0
      VS 5; P < 0.05), a lower decrease in hemoglobin (median,-0.6 VS -1.55 MG/DL; P <
      0.05), and a lower decrease in hematocrit (median, -0.03% VS -0.07%; P < 0.05).
      There were no significant differences in the frequency of postoperative
      complications (14.3% for LAVH VS 30% for AH). Although all LAVH patients who
      answered the questionnaire said they would undergo the same procedure again, only
      45% of the AH group were satisfied (P < 0.05). CONCLUSION: For the treatment of
      uteri >200 g, LAVH has several advantages over AH: lower postoperative morbidity,
      quicker short-term recuperation, and better patient acceptance.

PMID- 11961622
TI  - Does training in a virtual reality simulator improve surgical performance?
AB  - BACKGROUND: The development of computerized surgical simulators in a virtual
      reality environment demands models for proper validation. Recent investigations
      have shown that a virtual reality simulator (MIST-VR) is a reliable tool for the
      assessment of laparoscopic psychomotor skills and that it improves the automation
      of the so-called fulcrum effect. Therefore, we set out to determine whether
      training with the MIST-VR would improve the surgical performance of surgically
      inexperienced medical students and to see if results obtained in the simulator
      would correlate with surgical performance. METHODS: A total of 29 medical
      students were randomized into two groups. One group received preoperative MIST-VR
      training. Both groups then performed a simulated laparoscopic appendectomy in a
      pig. The operations were videotaped and examined by three independent observers.
      RESULTS: There was no significant difference in performance between the two
      groups. The performance with the MIST-VR correlated with the results in surgery.
      CONCLUSION: A method that can measure surgical skill, based on the scoring of
      independent observers who view videotaped performances, seems to be reliable.
      MIST-VR did not improve the surgical skills of the subjects, but the results with
      MIST-VR did predict surgical outcome.

PMID- 11961623
TI  - Evaluation of structured and quantitative training methods for teaching
      intracorporeal knot tying.
AB  - BACKGROUND: We evaluated the effectiveness of five training methods-four
      structured and one unstructured-for teaching intracorporeal knot tying. METHODS:
      Forty-three graduate students without prior laparoscopic experience were randomly
      assigned to one of five training groups, and their performance in 10
      intracorporeal knot tying trials was evaluated, using time to complete a knot as
      the outcome measure. RESULTS: The average knot tying times for the four
      structured groups were significantly faster than the unstructured group (p <
      0.0001). Among the four structured groups, the minimally invasive surgical
      trainer-virtually reality (MIST-VR) and the box trainer drills showed the most
      rapid improvements. The MIST-VR improved average suturing time from trial one to
      trial two (P = 0.05), the box trainer drills group improved from trial one to
      trial four (P = 0.01), and the other two groups showed slower improvements.
      Statistically significant correlations were observed between scores on MIST-VR
      tasks and average knottying times (R > 0.7, p < 0.05). CONCLUSION: Structured
      training can be useful for the development of laparoscopic skills. MIST-VR is a
      valuable part of this training, particularly in the objective evaluation of
      performance.

PMID- 11961624
TI  - Robotically assisted minimally invasive biliary surgery in a porcine model.
AB  - BACKGROUND: A robotic surgery system has the potential both to reduce the effects
      of tremor and fatigue and to enhance dexterity in the performance of complex,
      fine endosurgical tasks. We report a prospective study of robotically assisted
      minimally invasive biliary surgery in a porcine model using the Zeus robotic
      surgical system (Computer Motion, Goleta, Ca, USA). METHODS: For this study, 50
      kg domestic swine were used. Minimally invasive robotically assisted
      cholecystectomy was performed in 16 animals, either longitudinal or transverse
      common bile duct incision, T-tube placement, and suture repair of the common bile
      duct. Retrieval of 12 simulated bile duct calculi was attempted. Eight animals
      were monitored for 6 weeks postoperatively. Liver function tests and
      cholangiography were performed 2 and 6 weeks after surgery. RESULTS: The median
      setup time for the robotic system was 45 min (range, 10-120 min). The median
      operative time was 40 min (range, 25-60 min) for cholecystectomy and 80 min
      (range, 40-165 min) for bile duct dissection, exploration, and repair. Of 12 bile
      duct calculi, 11 were retrieved successfully. Cholangiography demonstrated no
      leaks, and the anastomotic stenotic index (diameter of the proximal bile duct
      divided by the diameter of distal bile duct) at 6 weeks was 0.98. The results of
      the liver function tests remained normal in all animals. One postoperative death
      unrelated to operative technique occurred. Complications included one minor
      splenic laceration and two intraoperative gallbladder perforations. CONCLUSIONS:
      Robotically assisted minimally invasive biliary surgery in this animal model is
      both feasible and safe. The Zeus system provides enhanced dexterity, which
      facilitates precise laparoscopic suture repair of small bile ducts.

PMID- 11961625
TI  - Time-action analysis of instrument positioners in laparoscopic cholecystectomy.
AB  - BACKGROUND: Instrument positioners can position and lock a laparoscopic
      instrument. This study uses time-action analysis to evaluate objectively whether
      IPs can substitute for a surgical assistant efficiently and safely. METHODS: In
      four hospitals, 78 laparoscopic cholecystectomies were randomly assisted by a
      surgical assistant or an instrument positioner (AESOP and PASSIST) The efficiency
      and safety of laparoscopic cholecystectomies were analyzed with respect to time,
      number and type of actions, positioning accuracy, and peroperative complications.
      A questionnaire evaluated the difficulties for each operation and the comfort of
      instrument positioner use. RESULTS: The PASSIST and AESOP were able to replace
      the surgical assistant during laparoscopic cholecystectomies without
      significantly changing either the efficiency or the safety of the operation. The
      questionnaire showed that the surgeons preferred to operate with an instrument
      positioner. CONCLUSION: This study assessed objectively that instrument
      positioners can substitute for a surgical assistant efficiently and safely in
      elective laparoscopic cholecystectomies.

PMID- 11961626
TI  - Unique minithoracotomy assisted by videothoracoscopy facilitates a maximal view
      even with a minimal wound for resection of primary lung cancer.
AB  - Resection for primary lung cancer with an unique minithoracotomy and use of
      videothoracoscopy is described. Through an incision of approximately 10 cm at an
      ausculatory triangle, the 5th intercostal thoracotomy is done following
      dissection of muscles. At the anterior and posterior portion of the 6th rib, the
      6th intercostal vessels and nerve were dissected and the rib was resected. This
      approach makes feasible opening of a thoracic window without injury to the nerve
      and removal of the rib. Thoracoscopy is introduced through a midaxillary wound of
      2 cm. We report nine patients in whom we achieved resection for primary lung
      cancer by using this approach. This technique facilitates a standard operation
      for lung cancer and an almost painless postoperative state.

PMID- 11961627
TI  - The role of video-assisted thoracoscopic surgery in the treatment of
      parapneumonic empyema after the failure of fibrinolytics.
AB  - BACKGROUND: Approximately 10% of patients treated with intrapleural instillation
      of fibrinolytics fail to respond and therefore need more invasive techniques,
      such as video-assisted thoracoscopic surgery (VATS). METHODS: During the period
      1994-99, we treated 20 consecutive patients with complicated parapneumonic
      effusion (CPE) and pleural empyema (PE) that did not resolve with urokinase
      instillation given through the chest tube in a dose of 100,000 IU diluted in 100
      ml of normal saline/daily for 3-5 days. The patients' ages ranged from 21 to 68
      years (median, 46); 14 were male and six female. All patients had pleural fluid
      pH <7.1, LACTATE DEHYDRAGENASE (LDH) >1000, glucose <40 mg/dl and were submitted
      to VATS. RESULTS: Complete drainage was observed in 17 patients (85%), in the
      other three (15%), the procedure had to be converted to open thoracotomy due to a
      thickened visceral pleural peel. The mean operative time was 80.3 min (range, 55
      140), and the mean duration of postoperative hospital stay was 7.5 days (range, 4
      19). CONCLUSION: We found that VATS is a safe, effective, and well-tolerated
      surgical procedure in CPE and PE patients who have failed to resolve with initial
      treatment with fibrinolytics.

PMID- 11961628
TI  - Chronic idiopathic thrombocytopenic purpura (ITP) is a surgical disease.
AB  - BACKGROUND: We designed a study to assess the safety and long-term efficacy of
      laparoscopic splenectomy (LS) for the treatment of chronic idiopathic
      thrombocytopenic purpura (ITP). METHODS: Over a period of 55 months, 104 patients
      underwent LS for chronic ITP. The perioperative course was documented and the
      long-term follow-up data were recorded. RESULTS: The mean age was 36.9 years
      (range, 8-83) and 72 patients were female. Patients were operated on with a mean
      platelet count of 110,000/ml. Fifty-one patients were operated on with a platelet
      count of < 100,000; 18 of them had a count of < 50,000/ml and 11 had a count of <
      10,000/ml. There were no conversions to laparotomy. Bleeding occurred in 14
      patients, and five of them received a blood transfusion. The mean operating time
      was 56.5 min (range, 25-240). There were minor complications in five patients and
      major complications in three. The mean hospital stay was 2.1 days (range, 0-13).
      Over a mean follow-up period of 36 months (range, 4-62), all but four patients
      were available for follow-up. Eighty-four patients are in complete remission.
      Seven patients are in partial remission, with a platelet count of 50,000-100,000
      ?ml without medical treatment. Eleven patients did not respond or relapsed
      following a short initial response; three of them underwent later removal of an
      accessory spleen, two with partial response. All but two relapses occurred within
      70 days of the operation. CONCLUSION: LS is safe and effective for the treatment
      of chronic ITP and yields excellent long-term results. Until another form of
      treatment emerges, LS should be considered the treatment of choice for this
      disease and recommended to the patient at an early stage of the disease.

PMID- 11961630
TI  - Pulmonary function after laparoscopic and open cholecystectomy.
AB  - BACKGROUND: Laparotomy causes a significant reduction of pulmonary function, and
      atelectasis and pneumonia occur after open cholecystectomy. In this prospective,
      randomized study, we evaluated the hypothesis that pulmonary function is less
      restricted after laparoscopic cholecystectomy (LC) than after open
      cholecystectomy (OC). METHODS: Sixty patients underwent laparoscopic (n = 30) or
      open (n = 30) cholecystectomy. The two groups did not differ significantly in
      age, sex, intraoperative findings, and preoperative pulmonary function. Pulmonary
      function tests, arterial blood-gas analysis, and chest radiographs were obtained
      in both groups before operation and on postoperative day 1. RESULTS: The forced
      expiratory volume in 1 s (mean +/- SD values; OC, 1.49 +/- 0.77 L/s; LC, 2.33 +/-
      0.80 L/s; p > 0.0001) and the forced vital capacity (OC, 2.40 +/- 0.66 L; LC,
      2.93 +/- 1.05 L; p > 0.01) were more suppressed in patients having OC than in
      those having LC. Similar results were found for the peak expiratory flow (OC,
      3.51 +/- 1.35 L/s; LC, 4.27 +/- 1.66 L/s; p > 0.05), expiratory reserve volume
      (OC, 0.73 +/- 0.34 L; LC, 0.92 +/- 0.43 L; p > 0.05), and the midexpiratory phase
      of forced expiratory flow (FEF25-75) (OC, 1.45 +/- 0.54 L/s; LC, 1.60 +/- 0.73
      L/s; NS). Laparoscopic cholecystectomy was associated with a significantly lower
      incidence of (30 vs 70%) and less severe atelectasis and better oxygenation.
      CONCLUSION: Pulmonary function is better preserved after LC than after OC.

PMID- 11961629
TI  - A prospective trial of analgesia following endoscopic totally extraperitoneal
      (TEP) inguinal hernioplasty.
AB  - BACKGROUND: The extraperitoneal instillation of bupivacaine has been shown to be
      superior to the use of a placebo for postoperative analgesia following endoscopic
      extraperitoneal inguinal hernioplasty. The objective of the present study was to
      compare the efficacy of postoperative analgesia by local wound infiltration to
      instillation of the extraperitoneal space with bupivacaine. METHODS: Between 1
      September 1999 and 2 June 2000, a total of 100 patients who underwent unilateral
      endoscopic extraperitoneal inguinal hernioplasties were recruited to receive
      either local wound infiltration with 10 ml of 0.5% bupivacaine (group I, n = 50)
      or instillation of the extraperitoneal space with 40 ml of 0.25% bupivacaine
      after mesh placement (group II, n = 50). Daily postoperative pain was assessed by
      visual analogue pain score on a scale from 0 to 10 at rest and upon coughing.
      Total amount of oral analgesic consumed and clinical outcomes of the two groups
      were compared. RESULTS: A comparison of daily pain scores of the two groups at
      rest and upon coughing showed no significant difference (p = ns). The mean number
      of oral analgesic tablets consumed were 3.2 +/- 0.5 (SEM) and 3.3 +/- 0.5 (SEM)
      in groups I and II, respectively (p = ns). During follow-up, asympatomatic groin
      collections were more common in group II (n = 4) than group I (n = 2) (p = ns).
      CONCLUSIONS: Compared to local wound infiltration with bupivacaine, the
      extraperitoneal instillation of bupivacaine did not bestow any additional
      analgesic benefits. Therefore, the routine infiltration of skin incisions with
      bupivacaine is recommended after endoscopic extraperitoneal inguinal
      hernioplasty.

PMID- 11961631
TI  - Nurse-led direct access endoscopy clinics: the future?
AB  - BACKGROUND: Many studies have shown that rectal bleeding is a good indicator of
      underlying colorectal pathology, and that ost of the lesions in patients
      presenting with rectal bleeding lie in the left side of the colon [1, 5, 9, 12,
      23, 26]. The recent acceptance of the nurse-practitioner by the National Health
      Service may allow the use of nurse-endoscopists to develop throughout the United
      Kingdom. This study aimed to audit a unique nurse-led direct-access nurse
      endoscopy service with regard to its efficacy and cost effectiveness, and to
      monitor patient satisfaction and direct referrals from the primary health sector.
      METHODS: A nurse-led open-access flexible sigmoidoscopy (OAFS) service for
      patients reporting fresh rectal bleeding was established at our center in
      February 1996. A prospective audit of sigmoidoscopic findings and a retrospective
      analysis of referral patterns from local general practitioners were conducted. A
      questionnaire survey of both patient and general practitioner satisfaction also
      was conducted at the same time. RESULTS: Since February 1996, 706 patients have
      been referred to our service. Rectal bleeding was by far the most common cause
      for referral, representing the dominant symptom in 92% of the referrals received.
      Although 99% of the patients underwent a complete sigmoidoscopic examination, 16%
      of these examinations were limited because of several factors combined. A cause
      for bleeding was identified in 91% of the patients, with 24% of them experiencing
      subsequent significant pathology. Of the patients surveyed, 99% were satisfied
      with the service provided. The results also show nurse-led OAFS to be a more
      effective use of financial resources, costing $90 less per patient than general
      practitioner referrals sent to a consultant for further action. CONCLUSIONS:
      Rectal bleeding is a good indicator of underlying colorectal disease. Most of the
      significant lesions presenting with this symptom are found in the left side of
      the colon. A nurse-led OAFS is safe, effective, and acceptable to patients. It
      also is more cost effective than a consultant-led service.

PMID- 11961632
TI  - The poor quality of information about laparoscopy on the World Wide Web as
      indexed by popular search engines.
AB  - BACKGROUND: This study was undertaken to determine the quality of information on
      the Internet regarding laparoscopy. METHODS: Four popular World Wide Web search
      engines were used with the key word "laparoscopy." Advertisements, patient- or
      physician-directed information, and controversial material were noted. RESULTS: A
      total of 14,030 Web pages were found, but only 104 were unique Web sites. The
      majority of the sites were duplicate pages, subpages within a main Web page, or
      dead links. Twenty-eight of the 104 pages had a medical product for sale, 26 were
      patient-directed, 23 were written by a physician or group of physicians, and six
      represented corporations. The remaining 21 were "miscellaneous." The 46 pages
      containing educational material were critically reviewed. At least one of the
      senior authors found that 32 of the pages contained controversial or misleading
      statements. All of the three senior authors (LKN, NAO, GAF) independently agreed
      that 17 of the 46 pages contained controversial information. CONCLUSION: The
      World Wide Web is not a reliable source for patient or physician information
      about laparoscopy. Authenticating medical information on the World Wide Web is a
      difficult task, and no government or surgical society has taken the lead in
      regulating what is presented as fact on the World Wide Web.

PMID- 11961633
TI  - The feasibility of hand-assisted laparoscopic aortic bypass using a low
      transverse incision.
AB  - BACKGROUND: Hand-assisted laparoscopy can be used to perform aortoiliac
      reconstructive procedures. This study aimed to evaluate the safety and
      feasibility of a hand-assisted aortofemoral bypass in patients with occlusive
      disease using a low abdominal transverse incision to reduce postoperative
      respiratory problems. METHODS: In 18 patients, a modified Pfannenstiel incision
      was performed. A hand-assist device was inserted, and the aorta was exposed using
      transperitoneal laparoscopy. Tunneling was performed under laparoscopic control.
      The anastomosis was always performed proximally to the inferior mesenteric
      artery. In three patients, the proximal anastomosis had to be performed
      laparoscopically. The indication for surgery was occlusive disease in 16 patients
      and a combination of an aneurysm and aortoiliac occlusion in 2 patients. RESULTS:
      Conversion was required in one patient (1/18). In 13 patients (13/18), the total
      operating time did not exceed 180 min, and 61% of the patients (11/18) could be
      discharged by postoperative day 5. None of the patients died perioperatively
      (0/18). Complications were observed in six patients (6/18). Only one of these
      patients had respiratory problems (1/18). The remaining five patients had local
      complications such as wound healing problems. The anastomosis was sutured
      laparoscopically in three patients (3/18). CONCLUSIONS: Hand-assisted laparoscopy
      can be performed safely using a low transverse abdominal incision. In our
      experience this laparoscopic access can reduce the incidence of postoperative
      respiratory problems and incision-related complications.

PMID- 11961634
TI  - Laparoscopic intragastric stapled resection of gastric submucosal tumors located
      near the esophagogastric junction.
AB  - BACKGROUND: Laparoscopic resection cannot be applied easily to tumors located
      near the esophagogastric junction or the pyloric ring. We evaluated our
      laparoscopic intragastric surgical technique for gastric submucosal tumors
      located near the esophagogastric junction and the results of a clinical study.
      MATERIALS AND METHODS: We performed our technique in six patients: one man and
      five woman with a mean age of 61 years. Using the laparoscopic procedure, after
      inflation of the stomach, we inserted two or three balloon-type ports into the
      stomach through the abdominal wall. RESULTS: A stapled resection of gastric
      submucosal tumors using a laparoscopic linear stapler was performed successfully
      in all the patients. Without exception, stapled resections were successfully
      performed. The mean operation time was 168 min, and the blood loss was minimal
      There were no intra- or postoperative complications. The mean postoperative
      hospital stay was 9.8 days. The mean maximal diameter size of the resected
      specimens was 2.4 cm. Histopathologic diagnoses were gastrointestinal stromal
      tumors in five cases and enterogenous cyst in one. There were no recurrences
      during a mean follow-up period of 27 +/- 11.6 months. CONCLUSION: Although we
      need to evaluate the long-term outcomes, our procedure is considered technically
      feasible, safe, and useful for the resection of gastric submucosal tumors located
      near the esophagogastric junction.

PMID- 11961636
TI  - Deep venous thrombosis after laparoscopic cholecystectomy and prevention with
      nadroparin.
AB  - BACKGROUND: Postoperative thromboembolic disease has been suggested to occur with
      higher frequency during laparoscopic cholecystectomy than during other
      laparoscopic procedures or conventional cholecystectomy. The aim of this
      prospective study was to evaluate the occurrence of deep vein thrombosis (DVT) in
      laparoscopic cholecystectomy patients, whether they were treated with low
      molecular-weight heparins or not. METHODS: All 238 laparoscopic cholecystectomy
      patients included in the study underwent pre- and postoperative venous duplex
      scanning of both legs. Subcutaneous Nadroparin was administred to 105 patients.
      The remaining 133 patients did not receive pharmacologic prophylaxis. The
      different risk factors for thromboembolic disease were distributed evenly between
      the two groups, except for the duration of general anesthesia. RESULTS: No
      patient had postoperative clinical manifestations of DVT or pulmonary embolism.
      In five patients, DVT was detected at duplex scan approximately 10 days after
      surgery. Four DVTs were found among the 133 patients who did not receive
      Nadroparin (1.68%). In the group with pharmacologic prevention, one patient
      manifested a DVT (0.42%), giving a total DVT incidence of 2.10% after
      laparoscopic cholecystectomy. The difference between the two groups was not
      significant (p = 0.27), but the results seem to indicate a tendency toward a
      lower incidence in the Nadroparine group. CONCLUSIONS: In the light of the study
      results, it seems advisable to use thromboembolic prophylaxis during laparoscopic
      cholecystectomy.

PMID- 11961635
TI  - Laparoscopic cholecystectomy in acute cholecystitis.
AB  - BACKGROUND: In the light of laparoscopic cholecystectomy increasingly applied to
      all forms of cholecystitis, this study aimed at evaluating the safety of
      laparoscopic cholecystectomy applied to all cases of acute cholecystitis, and at
      determining factors associated with the risk of conversion to open
      cholecystectomy. METHODS: The clinical, biochemical, radiologic, and operative
      data from 124 consecutive cases of acute cholecystitis were analyzed
      retrospectively to determine the complications and morbidity after operation. The
      data were analyzed further by univariate and multivariate analysis to identify
      factors associated with conversion. RESULTS: No major bile duct injury or
      mortality occurred. Bile leak from the stump of the cystic duct developed in four
      patients. These were managed successfully by endoscopic biliary stent placement.
      The mean duration of hospital stay was 3.8 days in the laparoscopic group and 8.2
      days in the open group. Of the 124 patients (18.5%), 23 underwent conversion to
      open cholecystectomy. Univariate analysis identified the following factors as
      associated with conversion: common duct dilation greater than 7 mm observed on
      ultrasound, (p < 0.05), pericholecystic collection seen on ultrasound (p <
      0.0001), emphysematous cholecystitis (p < 0.01), endoscopic retrograde
      cholangiopancreatographic evidence of Mirizzi syndrome (p < 0.05), and
      pericholecystic collection at operation (p < 0.0001). On multivariate analysis,
      only pericholecystic collection (p < 0.015) and gallbladder wall thickness
      greater than 5 mm (p < 0.013) were statistically significant. CONCLUSIONS:
      Laparoscopic cholecystectomy for acute cholecystitis can be applied safely to all
      comers, offering the advantage of a shortened hospital stay. Pericholecystic
      collection, as observed on ultrasound, is associated with a high risk of
      conversion to open cholecystectomy.

PMID- 11961637
TI  - Effects of carbon dioxide pneumoperitoneum on free radical formation in lung and
      liver tissues.
AB  - BACKGROUND: The purpose of this study was to investigate the possible effects of
      carbon dioxide (CO2) pneumoperitoneum on free radical formation and lipid
      peroxidation in the lung and liver tissues of rats. METHODS: For this study, 50
      male Sprague-Dawley rats were divided into five equal groups: control (group 1);
      sham operation (group 2); 5, 10, or 15 mmHg (group 3, 4, or 5) pneumoperitoneum
      with CO2 groups. At the end of the procedures, the rats were killed, and
      perfusion was performed via vena jugularis with cold Ringer's lactate. After the
      perfusion procedure, the lung and liver were harvested, and the supernatant
      fractions of the lungs and livers were assayed for superoxide dismutase (SOD),
      catalase (CAT), and malondialdehyde (MDA). RESULTS: Both the lung and liver CAT
      activities were elevated consistently and significantly in the order of the study
      groups, as compared with the previous groups (p < 0.01 for all comparisons). The
      lung and liver SOD levels were elevated in groups 4 and 5, as compared with the
      other groups (p < 0.05). The lung MDA was significantly higher in groups 3 and 4,
      but not in group 5. Significant elevation in liver MDA was noted only in the 5
      mmHg pnemoperitoneum group (p < 0.05). CONCLUSIONS: These results indicate that
      CO2 pneumoperitoneum applied with 5, 10, or 15 mmHg pressure increases the
      formation of free oxygen radicals, which is counterbalanced by increased SOD and
      CAT activities of the lung and liver tissues. This effect of CO2 pneumoperitoneum
      on free radicals and lipid peroxidation appears to be pressure dependent in rats.
      The mechanism underlying this pressure dependency is still under investigation.

PMID- 11961638
TI  - Liver metastases are less established after gasless laparoscopy than after carbon
      dioxide pneumoperitoneum and laparotomy in a mouse model.
AB  - BACKGROUND: Although the liver is the most frequent site of cancer recurrence
      after conventional open surgery for colorectal cancer, the effect of laparoscopic
      procedures with or without gas insufflation on the development of liver
      metastases is largely unknown. METHODS: Male BALB/C mice inoculated intraportally
      with colon 26 cells were randomized to undergo carbon dioxide pneumoperitoneum (n
      = 14), abdominal wall lifting (n = 14), or full laparotomy (n = 12), or to serve
      as control subjects without any procedures other than tumor inoculation (n = 13).
      RESULTS: The growth of liver metastases 14 days after surgery was enhanced after
      full laparotomy (p < 0.01) and pneumoperitoneum (p = 0.02), as compared with that
      in the control subjects, whereas there was no difference in the growth of liver
      metastases between abdominal wall lifting and the control condition (p = 0.99).
      CONCLUSIONS: These results suggest that the defense against liver metastasis is
      better preserved after the gasless procedure than after laparotomy and carbon
      dioxide pneumoperitoneum in the reported animal model.

PMID- 11961639
TI  - Is frozen section effective for diagnosis of unsuspected gallbladder cancer
      during laparoscopic cholecystectomy?
AB  - BACKGROUND: Although frozen section is recommended to prevent tumor dissemination
      following laparoscopic cholecystectomy (LC) for unsuspected gallbladder cancer,
      there are no reports concretely demonstrating its effectiveness and outcome.
      METHODS: Frozen section during LC was performed in 990 patients with gallstones.
      The sensitivity, specificity of frozen section, and false-negative cases were
      evaluated in comparison with postoperative entire cross sections. RESULTS: In
      frozen section, 983 cases were diagnosed as benign and 7 cases as malignant. Of
      the benign cases, cancer was discovered in 4 patients postoperatively in which
      frozen section was diagnosed as regenerative epithelial severe atypia.
      Sensitivity was 64% and specificity was 100%. Concerning the results of frozen
      section by p-TNM classification, cancer was diagnosed in 40% of Tis lesions,
      whereas it was found in 83% of T2 or T3 lesions. CONCLUSION: Frozen section is
      effective in cases with T2 or greater lesions for which conversion to radical
      surgery should be required.

PMID- 11961640
TI  - Improved usability of a new handle design for laparoscopic dissection forceps.
AB  - BACKGROUND: Recent studies have shown that the shape of most instrument handles
      causes user discomfort and that none of the handles currently available on the
      market satisfies all ergonomic criteria. Therefore, we designed a handle with
      improved usability; i.e., it is easier to manipulate and its use entails less
      risk of injury for the operator. The aim of this study was to demonstrate that
      the intended improvements of the new design were successful. METHODS: Six handles
      representative of the types that are currently available were compared with the
      new version. Eight surgeons used the seven handles during a precision task and a
      rough task in a pelvi-trainer. A questionnaire and video analyses were used to
      assess the usability of the handles. RESULTS: Based on the responses to the
      questionnaire, we determined that there were significant differences between the
      new handle and the Aesculap handle (means of rotation and angle between handle
      and shaft). No significant differences were found between the new handle and the
      five other handles. The video analyses (documenting extreme vs neutral wrist
      excursions) showed significant differences between the new handle and the six
      other handles. CONCLUSION: Compared to the six existing handles, the new handle
      has significantly improved usability; in particular, its hinged design obviates
      the need to make extreme wrist excursions.

PMID- 11961641
TI  - A magnetic probe to retrieve broken metallic parts of instruments during
      laparoscopic procedures.
AB  - To facilitate retrieval of metallic fragments out of the abdominal cavity during
      laparoscopic procedures, a semiflexible magnetic probe was devised. Efficacy and
      safety was demonstrated in two clinical cases without need for additional trocar
      placement or conversion to laparotomy.

PMID- 11961642
TI  - Development of an ultrasonically activated trocar system.
AB  - BACKGROUND: Although rare, visceral and vascular injuries related to the
      insertion of conventional laparoscopic trocars may have disastrous consequences.
      Most of these injuries are due to the high puncture force applied to the trocar.
      We present the results of an animal laboratory evaluation of a newly developed
      ultrasonically activated trocar. METHODS: A total of 40 punctures were made in
      four pigs with an average weight of 53 kg. An 11-mmHg pneumoperitoneum was
      created through a Veress needle. A 10-mm diameter trocar was inserted in the
      midline for a laparoscope. A series of five trocars were then inserted on each
      lateral wall under laparoscopic control. Twenty punctures were made with a
      conventional reusable 11-mm trocar (CT) whose tip was sharp and conical. Twenty
      punctures were made with an 11-mm ultrasonically activated trocar (UT), whose
      fequency was 23.5 KHz and amplitude 150 mm. The cutaneous incision was made large
      enough so that the skin did not interfere with the trocar insertion. The force
      applied to the trocar was measured with a push-pull gauge connected to a
      computer. The following data were recorded: maximal force applied to the trocar
      to obtain insertion of the tip through the abdominal wall, maximum abdominal
      pressure increase during trocar insertion, and time for abdominal penetration.
      RESULTS: The average time needed for trocar penetration was 12.8 s with CT and
      4.5 s with UT (p < 0.001). The average maximal force was 6.8 kgF with CT and 0.4
      kgF with UT (p < 0.001). The average abdominal pressure increase was 7.6 mmHg
      with CT and 0.8 mmHg with UT (p < 0.001). At 30 days, no necrosis was found.
      Pathological findings were similar in both groups. CONCLUSION: Ultrasonically
      activated trocars required less time and much less force to be inserted. This may
      be a breakthrough in the safety of trocar insertion.

PMID- 11961643
TI  - Intestinal obstruction from midgut volvulus after laparoscopic appendectomy.
AB  - We present the case of a 30-year-old man who developed a small bowel obstruction
      from an acute midgut volvulus 8 days after undergoing a laparoscopic
      appendectomy. There was no evidence of congenital malrotation or midgut volvulus
      on the initial computed tomography (CT) scan or at laparoscopy. Subsequently, a
      midgut volvulus developed in the absence of congenital malrotation.

PMID- 11961644
TI  - Dual-organ ablative surgery using a hand-assisted laparoscopic technique. A
      report of four cases.
AB  - In clinical situations where more than one procedure is required, a properly
      positioned hand-assist device can be used to obviate the need for two large
      incisions. We present four cases of hand-assisted laparoscopic nephrectomy
      combined with a simultaneous second organ extraction. Each of the four primary
      procedures, as well as one of the four secondary procedures, was performed using
      a hand-assisted laparoscopic technique. In two cases, the secondary procedure was
      performed with an open surgical technique through the hand-assist incision. For
      the remaining secondary procedure, we used a laparoscopically assisted technique.

PMID- 11961645
TI  - Successful laparoscopic fundoplication in children with ventriculoperitoneal
      shunts.
AB  - We reported successful laparoscopic fundoplication in 2 pediatric cases with VPS
      and discuss the safety and feasibility of the procedure. Case 1: A 13-year-old
      girl with VPS underwent laparoscopic fundoplication. Case 2: a 9-year-old boy
      with VPS underwent laparoscopic fundoplication. In both cases, laparoscopic
      Nissen fundoplication was performed with a standard five-port technique with a
      low pressure of a pneumoperitoneum. The VPS system had no effect on port layout
      and intraabdominal manipulation and no adverse complications were observed in
      either case. The effect of a pneumoperitoneum in the VPS system remains
      controversial, however, the author emphasized that advanced laparoscopic surgery
      can be performed safely with creating a low pressure of a pneumoperitoneum.

PMID- 11961646
TI  - Laparoscopic esophagogastrostomy: an alternative minimally invasive treatment for
      achalasia stage III.
AB  - BACKGROUND: The surgical treatment for stage III achalasia with markedly dilated
      and sigmoid-shaped esophagus is a matter of controversy. Some authors recommend
      esophagectomy as the primary treatment because they believe that Heller myotomy
      cannot improve dysphagia in such cases. We present a patient with achalasia stage
      III in whom we successfully performed a laparoscopic esophagogastrostomy with
      posterior semifundoplication. METHODS: Using a five-trocar technique, the
      esophagogastric junction and the distal esophagus up to the tracheal bifurcation
      were dissected. An endoscopic stapler (Endo-GIA II) was inserted through a small
      gastrotomy at the cardia, with one branch placed in the gastric fundus and the
      other, under esophagoscopic control, in the esophagus. By two consecutive stapler
      applications, a wide side-to-side esophagogastrostomy was created. To prevent
      gastroesophageal reflux, a posterior semifundoplication was performed. RESULTS:
      The operation time was 170 min. Oral food intake was started after radiologic
      control on postoperative day 7. Radiologic study showed rapid passage of the
      barium meal and no reflux through the gastroesophageal junction. CONCLUSIONS:
      Laparoscopic esophagogastrostomy with posterior semifundoplication represents an
      alternative to esophagectomy and laparoscopic Heller-Dor surgery. Because of the
      wide side-to-side anastomoses, there is no risk of persisting stenosis such as
      that reported for the Heller operation, and the procedure certainly is less
      invasive than esophagectomy. As compared with laparoscopic extramucosal myotomy
      using anterior Dor fundoplication, it presents about the same technical
      difficulties.

PMID- 11961647
TI  - Robotic-assisted laparoscopic cholecystectomy.
AB  - We report a case of laparoscopic cholecystectomy that was performed using a
      robotic surgical system. A 70-year-old woman underwent laparoscopic robotic
      cholecystectomy ZEUS, the robotic system used in our study, has three interactive
      robotic arms fixed to the side of the operating table. The arms are controlled by
      the surgeon, who sits at a remote computer console. The surgeon's movements can
      be scaled down, and tremor is filtered out. The robotic-assisted laparoscopic
      cholecystectomy was completed in 42 min. The time to set up the robot was 22
      mins. All of the surgically reproducible robotic maneuvers were performed without
      any particular difficulty. The robotic movements were stable, accurate, and
      reliable, as well as easy to control with precision. Our preliminary experience
      indicates that robotic laparoscopic cholecystectomy is safe and can be as fast as
      conventional laparoscopic cholecystectomy. However, further clinical applications
      of robotic surgery are needed to confirm this observation.

PMID- 11961648
TI  - Management of main bile duct injuries that occur during laparoscopic
      cholecystectomy.
AB  - The introduction of laparoscopic cholecystectomy in surgical practice resulted
      with an increased incidence of bile duct injuries and required new classification
      systems. This article presents six cases of major bile duct injuries that
      occurred in our first 1,000 laparoscopic cholecystectomies. Four female and two
      male patients (ages, 36-71 years) were detected to have major bile duct injuries.
      Laparoscopic dissection was difficult because of acute inflammation in four
      patients and fibrosis in two patients. These six cases were between laparoscopic
      cholecystectomies 26 and 377 performed by the operating surgeons. Three of the
      patients had type E2 injury according to the Strasberg classification: one
      detected intraoperatively and the other two postoperatively. All were treated
      with Roux-en-Y hepaticojejunostomy. The other three patients had type D injuries:
      two realized intraoperatively and one postoperatively. Two of these injuries were
      repaired primarily over a T-tube. The remaining patient, whose injury was
      realized intraoperatively, underwent nasobiliary drainage postoperatively. Only
      one patient had a complication associated with a trocar injury to the liver
      parenchima during the first operation. A hepatic abscess and external biliary
      fistula developed, which were treated conservatively. At this writing, all the
      patients are well and without problems after 2.5 to 6 years of follow-up
      evaluation. Difficulties in laparoscopic dissection because of severe
      inflammation or fibrosis resulted in injuries to our patients. We can underscore
      the fact that experience may not always protect from complications, and that
      conversion to laparotomy might have prevented some of these injuries. Patients
      with a minor injury and a controlled leak can be treated by a combination of
      surgical and endoscopic or radiologic techniques. The treatment plan must be
      individualized for every patient, depending on the injury type, presentation, and
      condition of the patient.

PMID- 11961649
TI  - Laparoscopic enucleation of an insulinoma of the pancreas tail.
AB  - A 29 year-old woman with a tumor of the pancreatic tail was referred to our
      institute. The tumor was confirmed to be a solitary benign insulinoma that
      protruded from the pancreas and was distant from the main pancreatic duct. A
      laparoscopic enucleation was performed with Laparoscopic Coagulating Shears
      (LCS). The postoperative course was uneventful. The laparoscopic enucleation for
      benign pancreatic tumor was thought to be a feasible procedure when the
      appropriate instruments were used.

PMID- 11961650
TI  - Spleen-preserving laparoscopic distal pancreatectomy with conservation of the
      splenic artery and vein for a large insulinoma.
AB  - We report a successful spleen-preserving laparoscopic distal pancreatectomy for a
      large insulinoma with conservation of the splenic artery and vein. The patient
      was a 48-year-old man with syncope due to hypoglycemia. Abdominal computed
      tomography (CT) and ultrasonography revealed a large 6-cm mass located in the
      tail of the pancreas. We adopted the laparoscopic approach to remove the tumor.
      After careful dissection and an accurate hemostasis between the pancreas and
      splenic vessels, laparoscopic distal pancreatectomy was carried out using a
      linear stapler. There were no perioperative complications. The patient was
      discharged uneventfully. He had no hypoglycemic episodes or abdominal symptoms
      during 8 months of follow-up. When performed by experienced laparoscopic surgeons
      in conjunction with intraoperative ultrasonography, spleen-preserving
      laparoscopic distal pancreatectomy with conservation of the splenic artery and
      vein is a technically feasible procedure for the treatment of benign lesions of
      the tail or body of the pancreas.

PMID- 11961651
TI  - Diagnosis and laparoscopic management of a fallopian tube torsion following
      Irving tubal sterilization: a case report.
AB  - Tubal torsion is a very rare but serious clinical entity. Its occurrence has been
      reported following Pomeroy tubal ligation and laparoscopic tubal cauterization.
      The following case report will be the first one describing a tubal torsion after
      an Irving tubal ligation in a patient who also had a history of pelvic
      inflammatory disease (PID). This study includes the presentation of a case of
      tubal torsion that is diagnosed and managed laparoscopically and the review of
      the literature through a computerized search of MEDLINE for relevant cases in the
      English literature published between January 1966 and July 1999. The patient is a
      26-year-old woman with a history of PID and Irving tubal ligation. She presented
      with a second episode of acute right lower quadrant pain. The patient underwent a
      diagnostic laparoscopy and was found to have a 6 x 5 cm hemorrhagic and necrotic
      fallopian tube consistent with torsion of the right tube. A right salipingectomy
      was done laparoscopically. Combination of PID and tubal sterilization in the
      medical history of a patient presenting with acute or intermittent pelvic pain
      may suggest tubal torsion.

PMID- 11961652
TI  - Laparoscopic exploration for pancreatic injury.

PMID- 11961653
TI  - Colovesical fistula secondary to laparoscopic transabdominal preperitoneal
      polypropylene (TAPP) mesh hernioplasty.

PMID- 11961654
TI  - Superficialization of hemodialysis access using a video-assisted procedure.
AB  - Brachiocephalic fistula is one of the main options to gain blood access for
      hemodialysis. Although the fistula is easy to establish, puncture becomes
      increasingly difficult because the cephalic vein runs deep and fibrous tissue is
      being continually deposited over the cephalic vein. Although superficialization
      i.e., the removal of fibrous tissue along the basilic vein-has been performed
      with conventional surgery, the long incision along the cephalic vein induces the
      buildup of hard fibrous tissue so that puncture may remain difficult even after
      the operation. To avoid this problem, we tried superficialization of hemodialysis
      access using a video-assisted procedure and obtained a good result.

PMID- 11961655
TI  - Laparoscopic management of large retroperitoneal lymphoceles complicating aortic
      surgery.
AB  - Retroperitoneal lymphocele is a rare but debilitating complication of aortic
      replacement with synthetic graft. The only effective treatment reported to date
      is surgical reexploration and ligation of leaking lymphatics. This report
      illustrates the successful management of two patients with large retroperitoneal
      lymphoceles formed after aortic surgery using laparoscopic techniques. The
      available literature is reviewed. Laparoscopic fenestration of the lymphocele and
      laparoscopically assisted ligation of the leaking lymphatics combined with
      internal drainage resulted in long-term relief of compression symptoms, as
      observed, respectively, over the 5-year and 3-month follow-up periods.
      Percutaneous catheter drainage before laparoscopic management was unsuccessful in
      both cases. In addition, the unique presentation of a large retroperitoneal
      lymphocele with intestinal obstruction is reported, and currently available
      treatment options are discussed.

PMID- 11961656
TI  - A novel technique for the laparoscopic resection of mesenteric cysts.
AB  - Mesenteric cysts are rare, invariably benign intraabdominal tumors. Optimal
      surgical management requires complete excision of these lesions. The advent of
      laparoscopic surgery has allowed resection of these cysts to be achieved without
      full laparotomy. However, laparoscopic resection necessitates drainage of the
      cyst within the abdomen to facilitate extraction of the cyst through the
      laparoscopic ports. This article describes a novel technique in which the cyst
      was partially aspirated as the initial surgical maneuver. This in turn allowed
      traction to be applied to the cyst wall, such that it could be drawn up into the
      epigastric port, to aid the further dissection and removal of the cyst from the
      peritoneal cavity.

PMID- 11961657
TI  - Laparoscopic resection of a functional paraganglioma in the organ of Zuckerkandl.
AB  - We describe the successful laparoscopic resection of a functional paraganglioma
      in the organ of Zuckerkandl. A 47-year-old man with hypertension and diabetes
      mellitus was found to have an abdominal mass beside the aorta. The tumor was
      diagnosed as a functional paraganglioma by diagnostic imaging and biochemical
      tests. We then performed a transperitoneal laparoscopic resection for removal.
      After freeing the left ureter, resecting the inferior mesenteric artery, and
      dividing the small blood vessels, the tumor was isolated and found to be
      preserved in its capsule. It was retrieved in a bag through an enlarged incision.
      The operation time was 450 min and blood loss was 410 ml. The postoperative
      course was uneventful and there has been no local recurrence or distant
      metastasis during the 18-month follow-up period. Laparoscopic resection of
      functional extraadrenal paragangliomas is technically feasible and safe if
      adequate pre- and intraoperative medical management and a careful, steady
      surgical technique are used.

PMID- 11961658
TI  - Cushing's syndrome secondary to adrenal adenoma during pregnancy.
AB  - Cushing's syndrome during pregnancy is rare because of the suppressive effect of
      excessive glucocorticoid on the female reproductive system. Adrenal adenoma is
      the most common cause of Cushing's syndrome during pregnancy. Surgical treatment
      by unilateral adrenalectomy was preferred during pregnancy before the advent of
      laparoscopic adrenalectomy. We describe two patients with Cushing's syndrome
      secondary to adrenal adenoma diagnosed during the first and second trimester,
      respectively, and successfully managed by different approaches of laparoscopic
      adrenalectomy--one patient upon diagnosis and one after pregnancy.

PMID- 11961659
TI  - Dieulafoy's lesion of esophagus.
AB  - Dieulafoy's lesion is a rare arterial malformation that can cause massive
      gastrointestinal hemorrhage. The lesion occurs most commonly in the proximal
      stomach. The esophagus is not a common location for this lesion. We present the
      case of a 25-year-old woman who was admitted to our emergency unit with the
      findings of hematemesis and melena. Early upper gastrointestinal endoscopic
      examination revealed a Dieulafoy's lesion, which was located in the distal
      esophagus. Endoscopic band ligation stopped the bleeding successfully. The
      patient was discharged 3 days after the band ligation without any complications.
      Dieulafoy's lesion may cause severe, life-threatening bleeding. Endoscopic
      diagnosis can be difficult because of the small size and obscure location of the
      lesion. An abnormally dilated artery that penetrates through the mucosa
      constitutes the etiology. Endoscopy plays an important role in the diagnosis and
      treatment of this pathology. Despite widespread awareness of this entity, it may
      present a real challenge for the endoscopist due to the small size and hidden
      location of the lesion. The endoscopic approach to occult gastrointestinal
      bleeding for the diagnosis of vascular malformations is accepted as a quick and
      safe diagnostic method.

PMID- 11961660
TI  - Peritoneal cystic mesothelioma.
AB  - A 43-year-old man complained that during the previous 2 years he had experienced
      a number of episodes of hepatic colic. After examination, we diagnosed a
      symptomatic cholelithiasis with a sclerosed and atrophic gallbladder. He
      underwent laparoscopic surgery. During the operation, we observed multiple
      peritoneal tumors that appeared to be metastases of a gallbladder cancer. The
      histological study demonstrated a benign chronic cholecystitis accompanied by
      multiple peritoneal cystic mesotheliomas, an extremely rare tumor in men. The
      etiology of cystic mesothelioma is still unclear. It has been suggested that they
      are really multiple inclusion cysts that result from a proliferative reaction
      within the peritoneal tissue; their continued proliferation might be caused by
      the continued persistence of an inciting factor. However, in our patient, the
      proliferation appeared to be related to an extensive peritoneal tissue reaction
      to the chronic gallbladder inflammatory process. We did not use sclerosing
      therapy because we had resected the gallbladder and most of the visible lesions
      laparoscopically; therefore, we had most likely eliminated the potential source
      of the inciting factor. Because it is very difficult during laparascopy to
      differentiate these benign quistic mesotheliomas from peritoneal metastases or
      tuberculous lesions, it is debatable whether the surgeon should continue or
      terminate the laparoscopic procedure in these ambivalent and potentially risky
      circumstances.

PMID- 11961661
TI  - Crack cocaine-related prepyloric perforation treated laparoscopically.
AB  - Perforation, which occurs in seven to 10 patients per 100,000 population
      annually, complicates 5-10% of peptic ulcers. Crack cocaine has been associated
      with many gastrointestinal disorders, including ulcer perforation. Crack-related
      gastroduodenal perforations, typically prepyloric, have been on the rise in the
      last decade. Suggested mechanisms include ischemia, motility disorders, increased
      air swallowing, platelet-related thrombosis, and increased ACTH and
      corticosterone secretion. A 28-year-old man presented with vomiting and sudden
      generalized abdominal pain 3 h after smoking a "rock" (a 100-mg cube of crack).
      Physical examination revealed generalized guarding, and plain films showed free
      intraperitoneal air. Laparoscopy confirmed the diagnosis of generalized
      peritonitis secondary to a 5-mm perforation of the prepyloric anterior wall of
      the gastric antrum. Omentum-patched primary closure and thorough abdominal
      irrigation were undertaken. The postoperative course was uneventful. Omeprazole
      and anti-H. pylori treatment, including erythromycin and metronidazole, were
      maintained for 8 weeks and 1 week, respectively. Although drug addicts are not
      easily compliant with long-term medical treatment, in the particular case of
      crack addiction, the vasoconstrictive and dismotility effects of cocaine may
      precipitate gastric necrosis and paralysis, respectively, in the case of
      vagotomy. Although distal gastrectomy was the wisest choice when open ulcer
      surgery was adopted, the laparoscopic treatment of perforated ulcer, with either
      suture or sutureless techniques, has been found to be comparable to open surgery
      with regard to postoperative morbidity, reoperation rates, and mortality. The
      potential advantages of laparoscopy include the avoidance of large incisions,
      less attendant pulmonary morbidity, less wound infection, and possibly fewer
      postoperative adhesions.

PMID- 11961662
TI  - The use of a personal digital assistant for wireless entry of data into a
      database via the Internet.
AB  - BACKGROUND: Researchers typically record data on a worksheet and at some later
      time enter it into the database. Wireless data entry and retrieval using a
      personal digital assistant (PDA) at the site of patient contact can simplify this
      process and improve efficiency. METHODS: A surgeon and a nurse coordinator
      provided the content for the database. The computer programmer created the
      database, placed the pages of the database on the PDA screen, and researched and
      installed security measures. RESULTS: Designing the database took 6 months.
      Meeting Health Insurance Portability and Accountability Act of 1996 (HIPAA)
      requirements for patient confidentiality, satisfying institutional Information
      Services requirements, and ensuring connectivity required an additional 8 months
      before the functional system was complete. CONCLUSIONS: It is now possible to
      achieve wireless entry and retrieval of data using a PDA. Potential advantages
      include collection and entry of data at the same time, easy entry of data from
      multiple sites, and retrieval of data at the patient's bedside.

PMID- 11961663
TI  - Adenovirus-E1A gene therapy enhances the in vivo sensitivity of Ewing's sarcoma
      to VP-16.
AB  - This study determined the effect of Ad-E1A gene therapy in vivo. TC71 cells (2 x
      10(6)) injected subcutaneously into nude mice resulted in tumor development (1-3
      mm) 6 days later. Animals were then treated with Ad-E1A or Ad-beta-gal (5 x 10(9)
      plaque-forming units) by intratumoral injection twice weekly for 2 weeks. Animals
      received 8 mg/kg VP-16 given by intraperitoneal injection daily for 5 days
      following the first week of treatment with Ad-E1A or Ad-beta-gal. Control animals
      received no therapy or VP-16 only after tumor cells were injected. When tumors
      exceeded 2 x 2 cm, the mice were sacrificed and the tumors underwent histologic
      and immunohistochemical analysis. Tumors from mice treated with Ad-E1A plus VP-16
      were 9.6-fold smaller than those treated with VP-16 alone and 6.3-fold smaller
      than those treated with Ad-E1A alone. HER2/neu p185 protein expression decreased
      in all tumors that received Ad-E1A therapy. TUNEL fluorescence staining revealed
      more apoptosis in the tumors from animals treated with Ad-E1A plus VP-16 than in
      those from animals treated with Ad-E1A alone, Ad-beta-gal plus VP-16, or VP-16
      alone. These data demonstrated that Ad-E1A gene therapy down-regulated HER2/neu
      expression, increased tumor cell apoptosis induced by VP-16, and enhanced tumor
      cell sensitivity to VP-16. Ad-E1A may have potential in the treatment of relapsed
      drug-resistant Ewing's sarcoma.

PMID- 11961664
TI  - Assessment of growth inhibition and morphological changes in in vitro and in vivo
      hepatocellular carcinoma models post treatment with dl1520 adenovirus.
AB  - BACKGROUND AND AIMS: E1B-deleted virus dl1520 (ONYX-015) has been previously used
      in clinical trials mainly for treatment of head and neck tumors, and has been
      shown to have beneficial effects independent of p53 status. The main aim of this
      investigation was to carry out a preclinical study for assessment of the use of
      dl1520 in in vitro and in vivo hepatocellular carcinoma (HCC) models with various
      p53 status (deleted, mutant, and wild type), and study the ultrastructural
      changes in the carcinoma cells during and following treatment with dl1520.
      METHODS: dl1520 (ONYX-015) virus was used for treatment of three HCC cell lines
      in culture, then for treatment of developed xenografts in SCID mice. The effects
      of dl1520 on HCC cell growth and accompanied morphological changes were assessed
      by various techniques including transmission electron microscopy. dl1520
      infection was confirmed using polymerase chain reaction and immunolabeling at
      transmission electron microscopy level. RESULTS: dl1520 was effective in killing
      cells and inhibiting HCC cell growth both in vitro and in vivo. The cell killing
      was at higher levels in cells possessing abnormal p53. Survival rates in SCID
      mice treated with dl1520 were statistically significantly higher in HCC tumors
      with deleted and mutant p53, than in tumors with wild-type p53. CONCLUSIONS: The
      findings in this study suggest that dl1520 could be safely and effectively used
      for treatment of HCC dependent on the p53 status of the cells in vivo.
      Characteristic morphological changes that took place in the dl1520-treated HCC
      cells/tumors were distinct at transmission electron microscopy level and are the
      first of their kind to be reported.

PMID- 11961665
TI  - The murine whey acidic protein promoter directs expression to human mammary
      tumors after retroviral transduction.
AB  - The whey acidic protein (WAP) promoter is known to be active in pregnant and
      lactating mammary epithelial cells as well as mammary tumors of mice. Here we
      show that a proximal fragment of the murine WAP promoter, including most elements
      postulated as being responsible for mammary-specific regulation, confers mammary
      specific expression upon a marker gene in transgenic mice even though the distal
      promoter region, known to be important for rat WAP promoter activity, is lacking.
      The relatively small size of this fragment allows its insertion into a murine
      leukemia virus-based retroviral vector in place of the viral promoter. Infection
      of a number of established human mammary and nonmammary cell lines with such a
      retroviral vector revealed that the WAP promoter was limited in its activity to
      mammary tumor cell lines. Expression in tumorigenic mammary cells was even more
      pronounced when these cells were introduced into the mammary fat pads of mice.
      This is the first demonstration that the WAP promoter is active in human mammary
      cells and mammary tumor cells in general, and suggests that the extended proximal
      WAP promoter may be useful for directing therapeutic gene expression to human
      mammary tumors.

PMID- 11961666
TI  - Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing
      the IP-10 chemokine into immunocompetent mice.
AB  - We have previously shown that the growth of human tumor xenografts in
      immunodeficient mice can be efficiently suppressed upon infection with the
      autonomous parvovirus H-1 or with cytokine-transducing derivatives thereof. To
      further evaluate the benefits of implementing parvoviruses in cancer gene
      therapy, we have created a new recombinant vector, MVMp/IP-10, transducing the
      immunoactive, antiangiogenic chemokine IP-10, and used this virus to treat
      syngeneic tumors grown in immunocompetent mice. Intratumoral/intraperitoneal
      administration of only 3 x 10(7) replication units of MVMp/IP-10 per animal
      strongly inhibited the progression of established H5V cell-induced vascular
      tumors, a highly malignant mouse model for human cavernous hemangioma and
      Kaposi's sarcoma. Retardation of recurrent tumor growth and suppression of life
      threatening metastatic dissemination to internal organs were accompanied by a
      striking delay in hemangioma-associated mortality. Parental MVMp did not have a
      significant effect under these conditions up to the dose of 10(10) infectious
      units/animal, but had strong antihemangiosarcoma activity when used to infect H5V
      cells ex vivo prior to implantation. In all cases, virus therapy was very well
      tolerated. Virus-induced suppression of hemangiosarcoma was dependent on host T
      cells and associated with intratumoral persistence of IFN gamma-expressing
      cytotoxic lymphocytes, and led to the reduced expression of hepatic plasminogen
      activator inhibitor-1 (PAI-1), a metastasis-linked marker. This proof of
      principle study demonstrates that MVMp/IP-10 can aid the treatment of vascular
      tumors and that autonomous parvovirus-based vectors can be considered potent
      tools for cancer gene therapy purposes.

PMID- 11961667
TI  - Transcription-targeted gene therapy for androgen-independent prostate cancer.
AB  - The Escherichia coli enzyme (purine nucleoside phosphorylase, PNP) gene is
      delivered directly into PC3 tumors by one injection of replication-deficient
      human type-5 adenovirus (Ad5). Expressed PNP converts the systemically
      administered prodrug, 6MPDR, to a toxic purine, 6MP, causing cell death. We
      sought to increase the specificity of recombinant Ad vectors by controlling PNP
      expression with the promoter region from the androgen-dependent, prostate
      specific rat probasin (Pb) gene. To increase its activity, the promoter was
      combined with the SV40 enhancer (SVPb). Cell lines were transfected with plasmids
      containing both a reporter gene, under SVPb control, and a reference gene
      cassette to allow normalization of expression levels. Plasmids expressed
      approximately 20-fold more reporter in prostate cancer than in other cells, but
      surprisingly, the SVPb element was both androgen-independent and retained
      substantial prostate specificity. Killing by Ad5-SVPb-PNP vector of cell lines
      cultured with 6MPDR for 6 days was 5- to 10-fold greater in prostate cancer than
      in liver or lung cells. In vivo, a single intratumoral injection of Ad5-SVPb-PNP
      (4 x 10(8) pfu), followed by 6MPDR administration twice daily for 6 days,
      significantly suppressed the growth of human prostate tumors in nude mice and
      increased their survival compared to control animals. Thus, the androgen
      independent, prostate-targeting Ad5 vector reduces human prostate cancer growth
      significantly in vitro and in vivo. This first example of an androgen-independent
      vector points the way toward treatment of emerging androgen-independent prostate
      cancer in conjunction with hormone ablation therapy at a time when the tumor
      burden is low.

PMID- 11961668
TI  - C-terminal deletion mutant p21(WAF1/CIP1) enhances E2F-1-mediated apoptosis in
      colon adenocarcinoma cells.
AB  - The present study was designed to investigate the efficacy of combination gene
      therapy using adenoviral vectors expressing gene products shown to possess
      apoptotic activity: E2F-1 (Ad-E2F-1) and a C-terminal deletion mutant of
      p21(WAF1/cIP1) (Ad-p21(-PCNA)), on growth inhibition and apoptosis of human colon
      cancer cells in vitro and in vivo. Marked E2F-1 and p21(-PCNA) overexpression in
      response to adenovirus infection was evident by Western blot analysis. IC(25)
      concentrations of each virus were used for each treatment in vitro to detect
      cooperative effects on cell death. Coexpression of E2F-1 and p21(-PCNA) resulted
      in an additive effect on cell death compared to infection with either virus
      alone. Cell cycle analysis, poly(ADP-ribose) polymerase (PARP) cleavage and
      analysis of cell morphology also revealed that coinfection with both Ad-E2F-1 and
      Ad-p21(-PCNA) enhanced cellular apoptosis compared to either virus alone.
      Interestingly, E2F-1 protein expression was markedly enhanced in the E2F-1/p21(
      PCNA) adenovirus combination compared to Ad-E2F-1 infection alone. However, these
      same effects were not evident in cells coinfected with Ad-E2F-1 and an adenovirus
      expressing wild-type human p21(WAF1/CIP1) (Ad-p21(WT)). The increase in E2F-1
      expression with coexpression of E2F-1 and p21(-PCNA) was not a result of
      increased E2F-1 protein stability, but was related to increased transcriptional
      activity from the CMV promoter. Cell cycle analysis revealed G1 arrest 72 hours
      following single-gene therapy with either the wild-type or mutant p21, whereas
      increased accumulation of cells in G2/M phase was demonstrated in the E2F-1
      overexpressing cells. In the combined therapies, E2F-1/p21(-PCNA) treatment still
      resulted in G1 arrest, but E2F-1 was able to counteract the G1 arrest when
      coinfected with p21(WT). These results provide further evidence of the importance
      of the p21:PCNA-binding domain in mediating the complex cell cycle interaction
      between E2F-1 and p21. Simultaneous intratumoral injection of Ad-E2F-1 and Ad
      p21(-PCNA) dramatically reduced tumor burden of SW620 xenografts compared to
      either treatment alone in our in vivo model but not in HT-29 colon cancer
      xenografts. When combined with Ad-p21(-PCNA), E2F-1 adenovirus therapy resulted
      in approximately 95% decrease in tumor volume of SW620 tumor xenografts compared
      with controls (P<.05). In conclusion, although simultaneous delivery of E2F-1 and
      p21(-PCNA) transgenes results in increased E2F-1 expression and enhanced
      apoptosis of both SW620 and HT-29 colon cancer cells in vitro, this combination
      was only effective in the treatment of SW620 metastatic colon cancer in vivo.
      This may represent a potentially useful combination gene therapy strategy for
      metastatic colon cancer.

PMID- 11961669
TI  - Application of interleukin-2-secreting syngeneic/allogeneic fibroblasts in the
      treatment of primary and metastatic brain tumors.
AB  - We found previously that mice injected intracerebrally (i.c.) with a mixture of
      malignant cells and allogeneic fibroblasts genetically engineered to secrete
      interleukin-2 (IL-2) survived longer than mice in various control groups. The
      primary goal of this study was to determine if an established i.c. glioma (Gl261)
      or breast carcinoma (SB-5b) could be treated by injection of IL-2-secreting
      allogeneic fibroblasts into the tumor region. As an additional objective, these
      results were compared with the effectiveness of injecting IL-2-secreting
      allogeneic fibroblasts prior to the introduction of the tumor cells as a means of
      preventing the development of an i.c. glioma or breast carcinoma. The results
      demonstrated that treatment of mice bearing an established i.c. glioma or breast
      carcinoma with IL-2-secreting allogeneic fibroblasts resulted in a prolonged
      survival. Furthermore, the results demonstrate a significant delay (P<.005) in
      the development of glioma in the animals treated with either allogeneic
      nonsecreting or IL-2-secreting fibroblasts prior to introduction of tumor cells.
      In addition, 50% of the animals pretreated with IL-2-secreting allogeneic
      fibroblasts injected subsequently with Gl261 glioma cells did not develop a
      tumor, whereas all of the animals injected with glioma cells alone and 92% of
      those treated with nonsecreting fibroblasts eventually died. Evidence also exists
      that long-term immunity was established in the treated animals because there was
      a significant prolongation of survival in comparison to naive controls (P<.01)
      for those animals without evidence of glioma that previously had been immunized
      with treatment cells when challenged again with tumor cells. In a parallel
      experiment, 62% of the animals pretreated with nonsecreting allogeneic
      fibroblasts and 75% of the animals pretreated with allogeneic IL-2-secreting
      fibroblasts subsequently injected with SB-5b breast carcinoma cells did not
      develop tumors. The results indicate that IL-2-secreting allogeneic fibroblasts
      can be effective in the treatment of an established brain tumor. These data also
      suggest that i.c. injection of allogeneic IL-2-secreting fibroblasts is effective
      in prevention of the development of a brain tumor when the fibroblasts are
      introduced into the same site where the tumor is subsequently injected.

PMID- 11961670
TI  - Tumor gene therapy by MVA-mediated expression of T-cell-stimulating antibodies.
AB  - Immune responses to tumor-associated antigens are often dampened by a tumor
      induced state of immune anergy. Previous work has attempted to overcome tumor
      induced T-cell anergy by the direct injection of vectors carrying the genes
      encoding one of a variety of cytokines. We hypothesised that the polyclonal
      stimulation of T cells, preferably through the TCR complex, would result in a
      cascade of cytokines associated with T-cell activation and would be best able to
      overcome T-cell anergy. Here we use the highly attenuated MVA poxvirus to express
      on tumor cells, in vitro and in vivo, either of three membrane-bound monoclonal
      antibodies specific for murine TCR complex. Using this system, we have expressed
      antibodies specific for the CD3 epsilon chain (KT3), TCR alpha/beta complex (H57
      597), and V beta 7 chain (TR310). Tumor cells bristling with these antibodies are
      capable of inducing murine T-cell proliferation and cytokine production. When
      injected into growing tumors (P815, RenCa, and B16F10), these constructs induce
      the activation of immune effector cells and result in the rejection of the tumor.
      Histological and FACS analysis of tumor-infiltrating leukocytes reveal that the
      injection of recombinant virus-expressing antibodies specific for the TCR complex
      attracts and activates (CD25(+), CD69(+)) CD4 and CD8 lymphocytes. This approach
      represents a novel strategy to overcome T-cell anergy in tumors and allow the
      stimulation of tumor-specific T cells.

PMID- 11961671
TI  - Intraperitoneal adenovirus-mediated suicide gene therapy in combination with
      either topotecan or paclitaxel in nude mice with human ovarian cancer.
AB  - A mouse model of human ovarian cancer was used to investigate the effect of
      adenovirus-mediated thymidine kinase gene therapy (gt) in combination with
      chemotherapy. One hundred sixty female CD-1 nu/nu mice were injected
      intraperitoneally with Ov-ca-2774 cells. Onset of intraperitoneal treatment with
      either topotecan (6 or 12 mg/kg) or paclitaxel (18 or 36 mg/kg) was on day 4 or 8
      and was repeated once after 4 days. Animals scheduled for gt received
      intraperitoneal application of adv/rsv-tk 1 day prior to chemotherapy and were
      subsequently treated with ganciclovir (gcv; 10 mg/kg, every 12 hours for 6 days).
      Survival was chosen as study endpoint. Whereas tumor burden had hardly any effect
      on survival, the lower dose of either cytotoxic agent was seen to be more
      effective than the higher one. In the topotecan group, an interaction between
      topotecan and gt was present. Survival was best for animals treated with low dose
      of topotecan only, the addition of gt reduced survival time significantly. With
      the higher dose, gt did not affect survival time. With paclitaxel, only slight
      effects of gt on the survival times were seen. Due to treatment toxicity, this
      animal model may be problematic for the evaluation of gt and chemotherapy
      combinations. The effect of dose varied strongly with time. Mice treated with
      high-dose chemotherapy had a substantially increased risk of dying in the time
      period following application, whereas this advantage of the lower dose
      disappeared later.

PMID- 11961672
TI  - Public health and primary care--arranged marriage or free love?

PMID- 11961673
TI  - The impact on health and risk factors of the diarrhoea epidemics in the 1998
      Bangladesh floods.
AB  - The 1998 flood in Bangladesh ravaged approximately 60% of the land and affected
      over 30 million people. The aim of this study is to examine the impact of the
      flood on the health of the communities affected and to explore factors associated
      with episodes of diarrhoea. We conducted structured interviews with 517 people in
      two districts that had been affected in October 1998, when the flood water level
      was at its peak. Of the 517 respondents, 98.3% developed health problems or found
      that existing health problems were exacerbated. Many perceived that their general
      health condition was 'much worse' (16.9%) or 'worse' (64.3%). The most prevalent
      condition was fever (63.6%), followed by respiratory problems (46.8%), diarrhoea
      (44.3%), and skin problems (41.0%). Only 1.0% and 6.7% of the respondents treated
      water before drinking, by boiling and chlorination, respectively, although water
      collected from tube-wells (93.2%) and rivers (6.0%) was perceived by 75.0% of the
      respondents to be contaminated. Factors associated with developing or worsening
      diarrhoea were as follows; the number of family members, poor economic status, a
      lack of distribution of water purification tablets, the type of water storage
      vessels, not putting a lid on the vessel, no use of latrines, perceived change of
      drinking water, food scarcity, and worries about the future. In logistic
      regression analysis, men, poor economic status, lack of distribution of water
      purification tablets, and the type of water storage vessels had a significant
      association with diarrhoea. The 1998 Bangladesh flood had a substantial impact on
      the health of communities. Diarrhoea was associated with socioeconomic status,
      water handling and household sanitation. There ought to be more emphasis on
      health education in the pre-disaster period in order to empower communities
      against floods.

PMID- 11961674
TI  - Surveillance of foodborne outbreaks of infectious intestinal disease in England
      and Wales 1992-1999: contributing to evidence-based food policy?
AB  - Between 1992 and 1999, a total of 1426 general outbreaks of infectious intestinal
      disease reported to the Public Health Laboratory Service (PHLS) Communicable
      Disease Surveillance Centre (CDSC) were described as foodborne. Where the
      evidence base to support the conclusions drawn was provided (66.3% of outbreaks)
      a combination of microbiological and analytical evidence was reported in 4% of
      outbreaks (60/1426); microbiological evidence alone in 10% of outbreaks
      (149/1426); analytical evidence alone in 23% of outbreaks (322/1426);
      microbiological evidence in combination with descriptive epidemiology in 3% of
      outbreaks (46/1426) and descriptive epidemiology alone in 26% of outbreaks
      (365/1426). Information supplied to CDSC by local investigators appears to be of
      varying quality and depth and may be influenced by the individual characteristics
      of outbreaks such as size and duration, outbreak setting, causative organism,
      vehicles of infection and time of year. These findings have implications for the
      use of these surveillance data in developing evidence-based food policy.

PMID- 11961675
TI  - Trends in lifestyle coronary risk factors in the Danish MONICA population 1982
      1992.
AB  - Myocardial infarction incidence rate declined 3-5% per year during 1982-1992 in
      the Danish study population of the WHO MONICA Project. We examined whether
      smoking habits, alcohol intake, dietary habits and physical activity levels
      changed in the population during the same period. Data from 6695 men and women of
      ages 30, 40, 50 and 60 y, examined in 1982-4, in 1986-7, and in 1991-2, were
      analysed to estimate trends. A summary healthy eating index and six scores
      derived by factor analysis were used to analyse food frequency data. The
      percentage of smokers declined 1.6% per year in men, and 1.0% per year in 30-, 40
      and 50-y-old women, but increased 0.9% per year in 60-y-old women. The
      percentages of heavy cigarette smoking men and women nevertheless remained
      constant and close to 30%. Total alcohol intake declined among 30-y-olds, but
      appeared constant in other age groups. However, among 60-y-old men and among
      women over 30, the percentage of wine-drinkers rose from 6-11% in 1982-4 to 9-18%
      in 1991-2. Only 60-y-old men became more physically active at work and only 30-y
      old women more so in leisure times. The percentage of individuals with a low
      healthy eating index decreased and the percentage with a high index increased.
      More importantly, dietary factor scores showed trends suggesting that very
      profound and potentially beneficial changes in dietary habits occurred. Lifestyle
      in the DAN-MONICA population changed in several ways that may have contributed to
      the declining incidence of myocardial infarction during the 1980s.

PMID- 11961676
TI  - Association of low maternal education with neural tube defects in Colorado, 1989
      1998.
AB  - Despite increasing use of folate prior to conception, neural tube defects remain
      among the most common birth defects in the United States. The Study objective was
      to investigate the maternal and child characteristics associated with having an
      infant born with a neural tube defect (NTD) in Colorado between 1989 and 1998.
      Data were derived from a population-based case control study of all live-born
      infants in Colorado from 1989 to 1998 (n=551,285), utilizing birth certificate
      records and a statewide neural tube defect registry. Chi-square analysis and
      multiple logistic regression were used to assess the strength of association
      between sociodemographic characteristics and the main outcome measure, the birth
      of a child with an NTD. Final analysis was limited to those children born to
      mothers who themselves were born in either the United States or Mexico. In this
      ten-year period, there were 251 confirmed cases of NTDs in Colorado, 224 of whom
      were born to women who were born in either the United States or Mexico.
      Significant bivariate associations were found between NTDs and the following:
      female sex of the child, lower maternal age, maternal country of birth in Mexico,
      and maternal education less than tenth grade. The single strongest predictor of
      having a child with an NTD was low maternal education (adjusted OR 1.8, 95% CI
      1.1-3.1). Low maternal education is an important predictor of having a child with
      an NTD. In order to further reduce the incidence of neural tube defects,
      interventions should target women of low educational status.

PMID- 11961677
TI  - Creating a measure of impact of childhood disability: statistical methodology.
AB  - The aim of the study was to develop a statistical method to derive a domain
      structure for the development of an impact of disability index, using
      multidimensional scaling of questionnaire items and expert and non-expert
      judgement of severity based on standardised videos. The participants were parents
      of children with cerebral palsy, parents of children in mainstream schools and
      clinicians with expertise in cerebral palsy, all accessed through child health
      services in the north east of England. The methods to create a weighted, domain
      structure for use with the impact of disability index were developed.
      Multidimensional scaling techniques can be used to derive dimensional data
      structures. Standardised video material can be used to elicit expert judgements
      of severity of disability.

PMID- 11961678
TI  - Caring for the health of the public: cross sectional study of the activities of
      UK public health departments.
AB  - The relative time spent in different areas of work in public health departments
      in the UK was assessed by means of a postal questionnaire. Departments spend one
      third of their time on population health work, this being similar to the amount
      of time spent on planning health services. Having a planning department in the
      health authority did not affect the amount of time spent in any area of work.
      Having a greater number of consultants in the department was associated with a
      tendency to spend more time on population health and being involved in training
      was associated with spending less time on planning. Public health departments in
      the UK are the only part of the health service with responsibility for the
      broader aspects of public health. Whilst the tensions between medical care and
      the wider influences upon population health may represent a false dichotomy,
      public health professionals must maintain a central focus of their work on the
      wider influences upon population health if balance is to be maintained within the
      National Health Service.

PMID- 11961679
TI  - The impact of an intervention to change health workers' HIV/AIDS attitudes and
      knowledge in Nigeria: a controlled trial.
AB  - The aim of the study was to improve health workers' skills and confidence in
      dealing with patients with HIV disease and increase attention to patients' human
      rights. A longitudinal controlled trial was carried out in which one Nigerian
      state served as the intervention site and the adjacent state served as the
      control site for an intervention and dissemination of training in clinical
      management, health education, and attitudinal change toward patients with HIV
      disease. The intervention group n=1072, control group n=480. Following initial
      questionnaire-defining focus groups, nurses, laboratory technologists and
      physicians in all base hospitals in the intervention state were trained by
      influential role models who attended the initial training. Data were collected in
      all sites pre-training and 1 y later. Hierarchical multiple regression analysis
      controlling for baseline data, and orthogonal factor analysis to define scales
      were used. Data showed significant positive changes after 1 y in the intervention
      group on perception of population risk assessment, attitudes and beliefs about
      people with HIV disease, less fear and more sympathy for and responsibility
      toward HIV patients, and an increase in self-perceived clinical skills. There was
      increased willingness to treat and teach colleagues about people with HIV.
      Clinician fear and discrimination were significantly reduced, and the climate of
      fear that was associated with HIV was replaced with a professional concern. There
      was increased understanding of appropriate psychosocial, clinical and human
      rights issues associated with HIV treatment and prevention. This intervention,
      targeting health workers in an entire state and using HIV/AIDS information, role
      modeling, diffusion of training and discussions of discrimination and human
      rights, significantly affected the perception of risk groups and behaviors,
      perceived skills in treatment and counseling, reduced fears and increased concern
      for people with HIV disease, and improved the climate of treatment and prevention
      of HIV disease compared with a control state.

PMID- 11961680
TI  - Oral fluid collection by post--a pilot study of two approaches.
AB  - This pilot study aimed to assess the feasibility of the postal collection of oral
      fluid samples for surveillance purposes and the effect of two different
      approaches on the response rates. This cross-sectional, antibody prevalence study
      collected oral fluid samples and questionnaire data from randomly selected
      individuals, aged under 45 y, through the post. The individuals were recruited
      from four general practice registers. In a one stage approach patients were sent
      the oral fluid kit with the initial invitation letter. In a two stage approach
      the kits were sent out after written consent had been received. There was little
      difference in the overall response rates between the two approaches (38% two
      stage and 41% one stage), though the response rate for the one stage approach was
      10% higher in the under-20-y-olds in practices from areas of greater deprivation.
      The low response partly reflected poor uptake in young adults who may need to be
      approached through more targeted surveys. In the other age groups additional
      reminders could prove a cost-effective way of increasing the response rate
      further.

PMID- 11961681
TI  - The implications of the Human Rights Act 1998 for the removal and detention of
      persons in need of care and attention.
AB  - The Human Rights Act 1998 ('HRA 1998') requires public authorities to act
      compatibly with the European Convention on Human Rights ('ECHR'). The ECHR
      contains rights, inter alia, to liberty and to respect for private life. Those
      rights--and, therefore, the HRA 1998--may be breached by provisions in the
      National Assistance Act 1948 and the National Assistance (Amendment) Act 1951
      that enable persons in need of care and attention to be removed compulsorily to
      hospital. However, legal proceedings brought against a public authority that
      invoked its statuatory powers of removal may themselves be defensible under the
      HRA.

PMID- 11961683
TI  - Trust, moral responsibility, the self, and well-ordered societies: the importance
      of basic philosophical concepts for clinical ethics.
AB  - Although the work of clinical ethics is intensely practical, it employs and
      presumes philosophical concepts from the central branches of philosophy,
      including metaphysics, epistemology, ethics, and political philosophy. This essay
      introduces this issue in the Journal on clinical ethics by considering how the
      papers and book reviews included in it illuminate four such concepts: trust,
      moral responsibility, the self and well-ordered societies.

PMID- 11961684
TI  - Trust in medicine.
AB  - Trust relations in medicine are argued to be a requisite response to the special
      vulnerability of persons as patients. Even so, the problem of motivating trust
      remains a vital concern. On this score, it is argued that a strong motivation can
      be found in recognizing that professional self-interest actually entails
      cultivation of patient trust as a means to maintain professional self-governance.
      And while the initial move to restore trust must be provoked from such narrow
      concerns, the process of sustaining trust will require educational initiatives
      aimed at restoring attitudes and skills suggestive of Percival's concept of
      empathic care. By including such initiatives, future waves of medical
      professionals are apt to sustain trust with deepened commitments to character,
      care, and trust as constitutive properties of their professional mission.

PMID- 11961685
TI  - Trust: the scarcest of medical resources.
AB  - In this paper, I claim that the doctor-patient relationship can be viewed as a
      vessel of trust. Nonetheless, trust within the doctor-patient relationship has
      been impaired by managed care. When we conceive of trust as social capital,
      focusing on the role that it plays in individual and social well-being, trust can
      be viewed as a public good and a scarce medical resource. Given this, there is a
      moral obligation to protect the doctor-patient relationship from the cost
      containment mechanisms that compromise its ability to produce trust.

PMID- 11961686
TI  - Is it wrong to deliberately conceive or give birth to a child with mental
      retardation?
AB  - This paper discusses the issues of deciding to have a child with mental
      retardation, and of terminating a pregnancy when the future child is known to
      have the same disability. I discuss these problems by criticizing a utilitarian
      argument, namely, that one should act in a way that results in less suffering and
      less limited opportunity in the world. My argument is that future parents ought
      to assume a strong responsibility towards the well-being of their prospective
      children when they decide to reproduce. The moral point in cases in which our
      acts affect the well-being of future children should be expressed strictly in
      terms of parents' culpability. Future children thus do not have current moral
      standing but presently living persons have current obligations to consider the
      presumable effects of their actions on future people. I will also argue that
      there are morally significant differences between 'selective contraception' and
      selective abortion.

PMID- 11961687
TI  - Dementia and dignity: towards a new method of surrogate decision making.
AB  - Autonomous decisions are decisions that reflect the self who makes them. Since
      patients in need of surrogate decision making can no longer enjoy the dignity of
      being free to express who they are through choice and action, surrogates should
      strive to, at least, make sure that decisions on behalf of the patient reflects
      that patient's self. Concepts of the self, then, underlie views about the role
      autonomy should play in surrogate decision making. Alzheimer's disease (AD)
      complicates the situation because it is a disease which effects the self and
      theorists disagree about which aspect of the AD self the decision should reflect.
      This disagreement has led to a seemingly irresolvable split between those who
      favor the then self and those who favor the now self. The debate has stalled
      because while both of these views are attractive, neither seems adequate. That
      is, neither view is complete because each focuses only on one aspect of a whole
      self. In this paper, I argue that a good mode of surrogate decision making is one
      that focuses on the whole self and I offer practical advice concerning how we can
      begin to think about how such a decision might be made.

PMID- 11961688
TI  - Moral status and the treatment of Dissociative Identity Disorder.
AB  - Many contemporary bioethicists claim that the possession of certain psychological
      properties is sufficient for having full moral status. I will call this the
      psychological approach to full moral status. In this paper, I argue that there is
      a significant tension between the psychological approach and a widely held model
      of Dissociative Identity Disorder (DID, formerly Multiple Personality Disorder).
      According to this model, the individual personalities or alters that belong to
      someone with DID possess those properties that proponents of the psychological
      approach claim suffice for full moral status. If this account of DID is true,
      then the psychological approach to full moral status seems to entail that the two
      standard therapies for treating DID might, on occasion, be seriously immoral, for
      they may well involve the (involuntary) elimination of an entity with full moral
      status. This result should give proponents of the psychological approach pause,
      for most people find the claim that current treatments of DID are ethically
      suspect highly counter-intuitive.

PMID- 11961693
TI  - AIDS and Africa. Introduction.
AB  - Sub-Saharan Africa is the epicenter of the HIV/AIDS epidemic, and in this issue
      of the Journal, seven authors discuss the moral, social and medical implications
      of having 70% of those stricken living in this area. Anton A. van Niekerk
      considers complexities of plague in this region (poverty, denial, poor
      leadership, illiteracy, women's vulnerability, and disenchantment of intimacy)
      and the importance of finding responses that empower its people. Solomon Benatar
      reinforces these issues, but also discusses the role of global politics in sub
      Saharan Africa, especially discrimination, imperialism and its exploitation by
      first world countries. Given the public health crisis, Udo Schuklenk and Richard
      E. Ashcroft defend compulsory licensing of essential HIV/AIDS medications on
      consequentialist grounds. Keymanthri Moodley discusses the importance of
      conducting research and the need to understand a moderate form of
      communitarianism, also referred to as "ubuntu" or "communalism", to help some
      Africans understand research as an altruistic endeavour. Godfrey B. Tangwa also
      defends traditional African values of empathy and ubuntu, discussing how they
      should be enlisted to fight this pandemic. Loretta M. Kopelman criticizes the
      tendency among those outside Africa to dismiss the HIV/AIDS pandemic, attributing
      one source to the ubiquitous and misguided punishment theory of disease. The
      authors conclude that good solutions must be cooperative ventures among countries
      within and outside of sub-Saharan Africa with far more support from wealthy
      countries.

PMID- 11961694
TI  - Moral and social complexities of AIDS in Africa.
AB  - In this article, the main complexities of understanding and curbing the HIV/AIDS
      pandemic in (South) Africa, are discussed. These are: 1. Poverty as niche or
      social context of the pandemic, 2. Denial, lack of leadership and the
      politicization of the public discourse on AIDS, 3. Problems related to
      accomplishing behavior changes under conditions of deprivation and illiteracy, 4.
      Women's vulnerability, and 5. The disenchantment of intimacy brought about by the
      pandemic. In each case, some solutions are suggested, although the notion of
      complexity does not allow for definitive solutions. Concluding remarks deal with
      the possible philosophical and moral sense that we might make of the pandemic.

PMID- 11961695
TI  - The HIV/AIDS pandemic: a sign of instability in a complex global system.
AB  - Intense scientific work on HIV/AIDS has led to the development of effective
      combination drug therapies and there is hope that effective vaccines will soon be
      produced. However, the majority of people with HIV/AIDS in the world are not
      benefiting from such advances because of extreme poverty. This article focuses on
      the pandemic as a reflection of a complex trajectory of social and economic
      forces that create widening global disparities in wealth and health and
      concomitant ecological niches for the emergence of new infectious diseases. While
      the biomedical approach to HIV/AIDS is necessary, has prolonged the lives of many
      individuals and could offer much at the level of population health, it cannot, in
      isolation, improve the health of populations. To achieve the latter will require
      understanding and addressing the deeper social causes of pandemics. Broadening
      the discourse on ethics to include public health ethics and the ethics of
      international relations could contribute to reducing the impact of the pandemic
      and to preventing the emergence of new infectious diseases in the future.

PMID- 11961696
TI  - Affordable access to essential medication in developing countries: conflicts
      between ethical and economic imperatives.
AB  - Recent economic and political advances in developing countries on the African
      continent and South East Asia are threatened by the rising death and morbidity
      rates of HIV/AIDS. In the first part of this paper we explain the reasons for the
      absence of affordable access to essential AIDS medication. In the second part we
      take a closer look at some of the pivotal frameworks relevant for this situation
      and undertake an ethical analysis of these frameworks. In the third part we
      discuss a few of the proposed solutions to the problem and conclude with an
      argument in support of our preferred course of action. In this article we argue
      for compulsory licensing of essential AIDS medications in the current conditions
      of public health emergency. We argue on broadly consequentialist grounds that
      compulsory licensing is preferable both morally and pragmatically to the
      alternatives, notably the currently offered price cuts and drug donation schemes.

PMID- 11961697
TI  - HIV Vaccine Trial participation in South Africa - an ethical assessment.
AB  - Trial participation in the proposed HIV Vaccine Trials in South Africa is
      discussed in the context of the ethical tension that exists between international
      ethical research standards and local standards of care and cultural norms in the
      Third World. The important concepts of informed consent, risk-benefit ratio and
      fair treatment of trial participants are interpreted differently in traditional,
      rural African communities, where a moderate form of communitarianism referred to
      as "Ubuntu" or "communalism" is still prevalent. Research is an altruistic
      endeavor that benefits communities and societies as a result of risks taken by
      individuals. Universal ethical guidelines that are highly individualistic and
      fail to emphasize communalism may represent serious problems for the sort of
      research needed in Africa today.

PMID- 11961698
TI  - The HIV/AIDS pandemic, African traditional values and the search for a vaccine in
      Africa.
AB  - The response to the HIV/AIDS pandemic in Africa has so far ignored important
      traditional African values and attitudes toward disease and commerce. These
      values and attitudes are significantly different from the libertarian, market
      driven, profit-oriented values and practices of important sectors of the Western
      world. To deal with this epidemic, the world should consider respect for, and
      possibly even adoption of those African values, which provide for people in
      genuine need, irrespective of their ability to pay. HIV/AIDS vaccine research
      indigenous to Africa is also not always taken seriously, and struggles to find
      adequate funding for such research within or outside of the continent have been
      extremely difficult. A better appreciation of knowledge systems and values
      indigenous to the African experience is important in the fight against the
      HIV/AIDS pandemic.

PMID- 11961699
TI  - If HIV/AIDS is punishment, who is bad?
AB  - HIV/AIDS strikes with the greatest frequency in sub-Saharan Africa, a region
      lacking resources to deal with this epidemic. To keep millions more people from
      dying, wealthy countries must provide more help. Yet deeply ingrained biases may
      distance the sick from those who could provide far more aid. One such prejudice
      is viewing disease as punishment for sin. This 'punishment theory of disease"
      ascribes moral blame to those who get sick or those with special relations to
      them. Religious versions hold that God punishes them in order to castigate,
      encourage virtue, warn, rehabilitate, or maintain some cosmic order. Its various
      religious and secular forms are untenable; they lack cogency, risk blaming people
      unjustly, and jeopardize compassionate care for people. These views are not only
      irrational but also dangerous because they influence policies and cost lives. We
      need to cooperate and respond as befits this global public-health disaster and
      not engage in the misguided and bad faith activity of dividing the world into the
      blameworthy and blameless.

PMID- 11961700
TI  - [Impairment of ventilatory parameters and exercise capacity in patients with
      pulmonary hypertension and chronic heart insufficiency].
AB  - BACKGROUND AND OBJECTIVE: Chronic heart failure often coincides with secondary
      pulmonary hypertension. In this study the influence of pulmonary hypertension on
      exercise capacity and ventilatory parameters in patients with chronic heart
      failure was examined. PATIENTS AND METHODS: 21 patients with chronic heart
      failure (six women, 15 men, mean age 55 +/- 10 years) and a left ventricular
      ejection fraction of 25 % +/- 5 % were studied by right heart catheterization,
      bodyplethysmography including carbonmonoxide diffusion testing and
      spiroergometry. Seven patients suffered from ischemic and 14 patients from
      dilative cardiomyopathy. Pulmonary hypertension (defined as pulmonary artery mean
      pressure > 25 mmHg) was found in ten patients. RESULTS: Patients with pulmonary
      hypertension showed a reduced vital capacity (75 % +/- 20 % of normal values vs.
      93 % +/- 14 % of normal values, p < 0.001), a lower forced expiratory volume in
      one second (FEV1 68 % +/- 21 % of normal values vs. 91 % +/- 15 % of normal
      values, p < 0.001), and a reduced carbonmonoxide-diffusing capacity (58 % +/- 21
      % vs. 77 % +/- 21 %, p < 0.001) compared to patients without pulmonary
      hypertension. Mean expiratory flow at 25 % and 75 % of the exspiration time was
      lower in patients with pulmonary hypertension (30 % +/- 13 % vs. 50 % +/- 29 %
      and 62 % +/- 25 % vs. 81 % +/- 20 %, each p < 0.05). In patients with pulmonary
      hypertension, the flow-volume diagram characteristically showed signs of "small
      airway disease". Spiroergometry revealed a significantly lower maximum oxygen
      uptake (12.5 +/- 2.1 vs. 15.2 +/- 4.1 ml/min/kg, p < 0.05), oxygen-uptake at the
      anaerobic threshold (9.7 +/- 1.6 vs. 12.0 +/- 3.0 ml/min/kg, p < 0.05), carbon
      dioxide ventilatory efficiency (EqCO2 38 +/- 9 vs. 31 +/- 3, p < 0.05) and
      ventilatory reserve (39 % +/- 22 % vs 51 % +/- 21 %, p < 0.05) in patients with
      pulmonary hypertension. CONCLUSION: In patients with chronic heart failure the
      presence of pulmonary hypertension leads to a reduction of exercise capacity and
      impaired ventilatory parameters. Lung functional testing reveals bronchial
      obstruction, "small airway disease" and a reduced ventilatory efficiency.

PMID- 11961701
TI  - [Choledochal cysts in adult patients--presentation and clinical course].
AB  - HISTORY: A 35-year-old male was admitted with recurrent acute pancreatitis of
      unknown origin. He was found to have a cystic lesion in the upper abdomen
      believed to be a pancreatic pseudocyst (patient 1). A 59-year-old female with a
      choledochal cyst developed acute pancreatitis (patient 2). A 32-year-old male who
      had been operated upon for a choledochal cyst during childhood was admitted for
      upper abdominal pain, fever and vomitus (patient 3). INVESTIGATIONS AND
      DIAGNOSIS: Patient 1 was found to have a choledochal cyst type IV a according to
      TODANI. Patient 2 was diagnosed to have a choledochal cyst type Ib according to
      TODANI. The cyst was believed to contain a bile duct carcinoma. In patient 3,
      sonography showed an advanced Klatskin tumour with infiltration of the portal
      vein, the hepatic artery and the liver. Bile cytology confirmed the carcinoma. In
      all patients cholestasis was found. Pancreatic enzymes were elevated in patients
      2 and 3. TREATMENT AND COURSE: Patient 1 underwent left hemihepatectomy and
      received a biliodigestive anastomosis. In patient 2 the choledochal cyst was
      resected while undergoing pylorus-preserving resection of the pancreatic head.
      The tumour suspected was confirmed and R0 resected. Patient 3 presented with an
      incurable bile duct carcinoma. He died 3 months later from multiple lung emboli.
      CONCLUSION: Choledochal cysts are associated with a 20 fold increase in the
      incidence of bile duct carcinoma.

PMID- 11961703
TI  - [Diagnosis of leukoencephalopathy].

PMID- 11961704
TI  - [The value of low-molecular-weight heparins in the treatment of acute coronary
      syndrome].

PMID- 11961702
TI  - [Cushing's syndrome caused by paraneoplastic ACTH secretion 11 years after
      occurence of a medullary thyroid carcinoma].
AB  - HISTORY AND ADMISSION FINDINGS: A 47-year-old man, with known and treated
      hypertension for 2 years, was admitted because of recent marked weight gain.
      Eleven years before a medullary thyroid carcinoma had necessitated removal of his
      thyroid and parathyroids. He was not receiving levothyroxine, calcium and vitamin
      D. Physical examination revealed florid Cushing's syndrome with a "buffalo hump",
      plethora, truncal obesity and red striae. Both his mother and a maternal male
      cousin were reported to have had a medullary thyroid carcinoma. INVESTIGATIONS:
      Plasma ACTH was 80 pg/ml (normal 10-70 pg/ml), urinary cortisol 764 microgram/24
      h (normal 20-100 microgram/24 h). ACTH rose to 93.1 pg/ml after dexamethasone,
      with little suppression of serum cortisol (reduced from 34.4 to 22.1
      microgram/dl; normal 7-25 microgram/dl. Magnetic resonance imaging did not
      detected an abnormal hypophysis. Petrosal sinus catheterization revealed
      hypophyseal suppression of ACTH, without evidence of focal peripheral ACTH
      production. Calcitonin was 24 000 pg/ml (normal < 8.8 pg/ml). Computed tomography
      showed multiple round lesions in the liver (histology: metastasis of a C-cell
      carcinoma). Genetic test showed a multiple endocrine neoplasm type IIa.
      DIAGNOSIS, TREATMENT AND COURSE: The findings indicated Cushing's syndrome, most
      likely due to paraneoplastic ACTH secretion from a metastasis of the C-cell
      carcinoma. In the absence of a site of paraneoplastic ACTH secretion, bilateral
      adrenalectomy was performed. The plethora and striae regressed postoperatively
      and it was possible to reduce markedly the antihypertensive medication.
      CONCLUSION: An ectopic site of ACTH should be included in the differential
      diagnosis of Cushing's syndrome. This is the first reported case of a medullary
      thyroid carcinoma and ectopic ACTH production in which the paraneoplastic ACTH
      secretion had been delayed for 11 years.

PMID- 11961705
TI  - [Medical indication for inducing death?].

PMID- 11961706
TI  - [Which therapy is meaningful for atrial septal aneurysm TIA and persistent
      foramen ovale?].

PMID- 11961707
TI  - [Recurring corneal lesions during cholesterol synthesis enzyme inhibitor
      administration?].

PMID- 11961708
TI  - [Sleep disorders caused by electrosmog?].

PMID- 11961709
TI  - [On the history of the self-help and advocacy movement of the families of
      mentally ill people].

PMID- 11961710
TI  - [Facts the Relatives have Taught me].

PMID- 11961711
TI  - [Children of psychotic parents].
AB  - OBJECTIVE: A focused review of a selected part of research on psychotic parents'
      children is being provided. The paper presents a general survey of high-risk
      studies followed by a critical discussion of some of the research being done
      about the relatives of psychotic people. This discussion is inspired and guided
      by a crucial interest in the subjective dimension of biography. RESULTS: It will
      be shown that there is only very little research being done on the perspective of
      the involved people themselves. The tradition of Bleuler and Anthony, demanding a
      strong shift to questions of resilience and coping, is being considered only
      hesitatively. On the other hand, qualitative research drawing on hermeneutic
      methods seems to be restricted to case studies mainly. CONCLUSIONS: Children's
      capacity to integrate their experiences with a psychotic parent into their own
      lives very often shows up in biographic narratives. Thus it is accessible to a
      methodologically elaborated qualitative analysis. Considering the growing
      interest in children being affected by their parents' psychosis - especially in
      their ability to cope with their specific situation - the paper pleads for more
      extensive research on the biographies of these people and the narratives shaping
      them.

PMID- 11961712
TI  - [A family day clinic in child psychiatry. The Dresden model--concepts and first
      experiences].
AB  - AIMS: To present a systemic family therapy approach for children with psychiatric
      disorders, based on multiple family therapy principles and employing video
      feedback and peer review techniques. Children and their parents together attend a
      family day clinic for periods of between 3 and 14 weeks. METHOD: We report on
      conceptual and clinical work, with case examples and discussion of a pilot study.
      RESULTS: At 6 months follow-up there are symptomatic and behavioural improvements
      in 75 % of the children and 90 % of the parents. CONCLUSIONS: Active involvement
      of parents in the therapy of their children appears to lead to better and longer
      lasting treatment results. Extensive interdisciplinary work between adult and
      child psychiatric services is needed, particularly with the more severe spectrum
      of parental psychiatric disorders.

PMID- 11961713
TI  - [Psychoeducational groups for families of in-patients with affective disorder].
AB  - OBJECTIVE: Experiences with psychoeducational groups have been extensively
      reported for schizophrenic patients and their families. For patients with
      affective disorders, however, only a few publications exist. We describe results
      and conclusions for clinical practice with a type of psychoeducational group that
      addresses family members of in-patients treated at a specialized depression ward.
      The group sessions are every other week and we try to take up the questions asked
      by the attenders in order to concentrate on their personal needs. METHODS:
      Protocols of 40 group sessions over 18 months were analysed concerning attendance
      figures, degree of relatedness to the patient, main topics and questions, and
      emotional condition of the participants. RESULTS: The 40 group sessions were
      attended by 400 participants (mean = 10; median = 9). About 50 % of them were
      spouses. For the other family members, there was a clear association between
      female patients and female attenders. Main question was how to deal with the
      patient, at present and after discharge. With regard to the emotional state, 23 %
      were under strain themselves, 7 % were skeptical and 23 % could be described as
      relieved. CONCLUSIONS: This kind of group reaches a considerable number of family
      members, who in general highly appreciate these sessions. The therapeutic team
      also benefits from enlarging their knowledge by including the relatives'
      perspective. Therefore, the effort for preparing and holding the group session
      seems to be justified and rewarding. To our opinion, good attendance figures can
      be reached by personal invitation of the relatives and by being flexible and
      oriented towards their needs.

PMID- 11961714
TI  - [Behavioral Group Therapy for Patients with OCD and Family Members].
AB  - PROBLEM: Behavioral group therapy program is presented of patients with OCD and
      the involvement of their significant others. First experiences of evaluation are
      reported. METHOD: 20 patients (10 women, 10 men) diagnosed with OCD were treated
      in a 16-session behavioral group therapy which included the involvement of 17
      family members in selected sessions. The behavioral group therapy program
      involved cognitive restructuring, behavior exposure to anxiety-evoking stimuli
      and the discussion about the family system. Y-BOCS and a self-rating scale for
      the assessment of treatment benefit were used as outcome measures. RESULTS: In
      this study, Y-BOCS scores reduced from a mean of 24 before therapy to 19,8 after
      therapy. Patients and their significant others agreed on the general benefit from
      the group therapy and the level of understanding of individual problems. Family
      members in particular appreciated that they had learned more about coping
      strategies regarding OCD-symptoms.The majority of patients and their significant
      others would recommend behavioral group therapy to other affected people.
      CONCLUSIONS: Behavioral group therapy can be effective in reducing OCD-symptoms.
      Inclusion of family members in behavioral group therapy may be advantageous,
      because they can assist the patients during their treatment. This form of
      treatment may become an attractive and cost-effective alternative to conventional
      group settings.

PMID- 11961715
TI  - [Family caregivers of patients with dementia: impact of factors of burden].
AB  - OBJECTIVES: The enclosed paper tries to encompass the relatives of patients of
      three different geriatric groups diagnosed. It tries to establish the difference
      in care and which special factor influences each group concerning the burden of
      care. PATIENTS: Comparison of three groups: 1. Alzheimer-dementia, 2. vascular
      dementia, 3. nondemented patients. RESULTS: It was found that it is mostly
      partners and children who are the carers in all three groups diagnosed. The
      social behaviour of the Alzheimer patient is the most stressful part of caring.
      The relatives of patients with vascular dementia are most stressed by disturbing
      behaviour and memory impairment and the relatives of the non dementia group by
      impaired mood and inadequate behaviour. CONCLUSIONS: The burden of care is the
      hardest for the relatives of the Alzheimer patients. For all three groups
      diagnosed the non cognitive symptoms are the main factor of the carers burden.

PMID- 11961716
TI  - [The course of illness and problems of schizophrenic women and men from the
      relatives' perspective].
AB  - OBJECTIVES: Members of HPE, an Austrian self-help organization for the relatives
      of mentally ill people, were questioned about their opinion with regard to the
      situation of families with a mentally ill member. METHODS: A questionnaire was
      sent to the addresses of members of this self-help organisation. 182 respondents
      reported to care for 132 male and 50 female sufferers diagnosed as having a
      psychosis from the schizophrenic spectrum replied. RESULTS: Relatives, who care
      for male sufferers reported greater distress than those caring for females.
      Depression and exhaustion are reported significantly more frequently in
      caregivers of males. Other burdens, for example financial burdens, to assist the
      sufferer in the household, renunciation of holidays, and the problem of neglect
      also have a tendency to be more common among those caring for men. These gender
      differences cannot be accounted for by differences in the course of illness. Our
      study showed no evidence of gender differences in this regard. Contrary to our
      expectations women in our study are less compliant with medication and
      psychosocial treatment. CONCLUSIONS: Despite a better compliance with treatment
      strategies among men, relatives of males generally experience a greater burden.
      Our results indicate a greater need for the development of independence
      strategies for male sufferers and a requirement that professionals support
      sufferers and carers in this direction.

PMID- 11961717
TI  - [Prognosis of schizophrenia from the viewpoint of patients and relatives. An
      explorative study].
AB  - OBJECTIVE: This study is aimed at exploring what schizophrenic patients and their
      closest relatives expect the further course of the illness will be like and how
      it can be influenced. METHOD: Problem-centered interviews were conducted with 31
      schizophrenic patients and their closest relatives at discharge from hospital
      treatment. The verbatim transcripts of the interviews were analyzed by means of
      structuring qualitative content analysis. RESULTS: Most frequently, the
      respondents expected an improvement of the illness or they were unsure whether
      the actual recovery from psychosis will persist or whether a further relapse will
      occur. Less frequently, the respondents were sure that this will be the case or
      that the illness will take a chronic, eventually deteriorating course. The
      majority was convinced that the course of the illness can be influenced, by
      psychiatric treatment as well as by the patients themselves. As concerns the
      social situation in the near future, particularly changes of the occupational
      status were hoped for. CONCLUSION: The assessment of the prognosis of the
      schizophrenic illness by most patients and relatives appears quite realistic.
      Rather than considering themselves as helpless victims they see opportunities for
      influencing the further course of the illness. This should have a positive
      influence on the readiness to use mental health service and to comply with
      treatment recommendations.

PMID- 11961718
TI  - [Psychoeducational group for patients with depression and their families].
AB  - Psychoeducation is an important part in the therapy of mental diseases. Until now
      there is little experience with patients and their family members attending the
      same psychoeducational group. We work with a psychoeducational group for
      depressed patients and their families. The aims are support and relief for the
      family, information about the affective disorder and acquisition of skills to
      improve the relationship between patients and family members. Every three months
      we start a new group with three sessions. At the first session we give
      information about symptoms, the disease and prognosis. At the second meeting we
      discuss the causes and how to deal with the disorder. The contents of the last
      session are the treatment and recidive prophylaxis. In the time from winter 1998
      to spring 2000 six different groups have taken place with 101 patients and family
      members as participants. There was a high continuity of participation and a
      positive feed-back of the members. We can recommend this kind of
      psychoeducational group for other psychiatric hospitals. Patients and their
      family members can come to terms with this illness and become experts on
      depression.

PMID- 11961719
TI  - [Ante portas: Contrast agents in routine ultrasound examination].

PMID- 11961720
TI  - [Evaluation of Doppler sonographic criteria for the differentiation of
      hepatocellular carcinomas and regenerative nodules in patients with liver
      cirrhosis].
AB  - AIM: In order to improve the differentiation between hepatocellular carcinomas
      and regenerative nodules in patients with liver cirrhosis, Doppler-sonographic
      criteria for the tumours were evaluated. METHOD: Patients with histologically
      proven hepatocellular carcinoma (n = 35) and regenerative nodules (n = 10) were
      investigated by B-mode sonography as well as fundamental and echo-enhanced power
      Doppler sonography focusing on specific properties of the tumours. The results
      were correlated to the histological findings. RESULTS: Hepatocellular carcinomas
      and regenerative nodules showed a different contrast behaviour with echo-enhanced
      power-Doppler sonography. The following features of hepatocellular carcinomas
      were frequently found: peritumoural signal detection in the early arterial phase,
      chaotic and centripetal contrast enhancement in the arterial phase,
      hypervascularization in the capillary phase, and loss of portalvenous blood flow.
      CONCLUSION: Hepatocellular carcinomas and regenerative nodules display different
      vascularization patterns in the echo-enhanced power-Doppler sonography. These
      characteristics can be useful for their differential diagnosis.

PMID- 11961721
TI  - [Hepatic transit time of an ultrasound echo enhancer indicating the presence of
      liver metastases - first clinical results].
AB  - AIM: This pilot study examines the question whether the transit time of an
      ultrasound echo enhancer, measured between the hepatic artery and the liver vein,
      can be used to differentiate between patients with and without liver metastases.
      METHOD: The hepatic transit time of an ultrasound echo enhancer (Optison(R)) was
      determined using the pulse-inversion mode in patients suffering from
      gastrointestinal tumours. A group with histologically verified liver metastases
      was compared to a group without liver metastases. RESULTS: 24 patients have been
      included in the study so far. 7 patients had liver metastases from a still
      existing primary tumour (group A). Five patients showed liver metastases after
      removal of the primary tumour (group B). Six patients had a primary tumour, but
      no liver involvement (group C), and six patients had neither a primary tumour nor
      any liver disease. The mean hepatic transit time in group A and B came to 7.4
      seconds. Group C and D had a transit time of 16 and 15.5 seconds, respectively.
      This shows a significant difference in hepatic transit time between patients with
      liver metastases (groups A and B) compared to those without (groups C and D). The
      presence of a primary tumour did not influence hepatic transit time. CONCLUSION:
      In this first pilot study using the measurement of hepatic transit time it was
      possible to differentiate between patients with and without liver metastases.

PMID- 11961722
TI  - Role of ultrasonography in the detection of small adrenal masses.
AB  - AIM: Computed tomography (CT) scanning is commonly used for evaluation of adrenal
      masses in adults. In this prospective study we evaluated whether adrenal gland
      masses of less or equal than 20 mm in diameter could be detected by modern
      abdominal ultrasonography (US). METHOD: Between July 1999 and June 2000, 44
      consecutive patients with 50 adrenal masses documented by contrast-enhanced CT
      (left adrenal gland, n = 31; right adrenal gland, n = 19; bilateral, n = 6;
      median size, 15 [5 +/- 80] mm) and, additionally, 50 patients without CT findings
      of an adrenal mass were prospectively evaluated by high-resolution US performed
      by physicians. Based upon CT measurement, 34 adrenal masses were </= 20 mm and 16
      were > 20 mm in diameter. RESULTS: The overall sensitivity of US for the
      detection of adrenal masses was 96 % (48/50) (94 % [29/31] for left and 100 %
      [19/19] for right adrenal masses, respectively). The overall specificity of US
      for the detection of adrenal masses was 92 % (92/100) (90 % [45/50] for left and
      94 % [47/50] for right adrenal masses, respectively). Thus, the diagnostic
      accuracy of US for the detection of adrenal masses is 93 % (140/150). Sensitivity
      and specificity of US for the detection of adrenal masses </= 20 mm (n = 34) did
      not differ significantly from those > 20 mm (n = 16). CONCLUSION: US is effective
      for detecting small adrenal masses. In rare cases small masses of the left
      adrenal gland might be missed and nodular adrenal hyperplasia or retroperitoneal
      lymph nodes might be misinterpreted as adrenal masses.

PMID- 11961723
TI  - [3D-ultrasound: a valuable adjunct for therapy planning and follow-up of head and
      neck tumours].
AB  - AIM: The three-dimensional visualization of orofacial tumours and adjacent organs
      at risk of infiltration is an important requirement for staging, therapy planning
      and follow-up. Artifacts from the mandible or metal implants often reduce the
      diagnostic power of computed tomography (CT). The value of 3D-ultrasound (3D-US)
      in respect to the standard methods CT and magnetic resonance imaging (MRI) was
      therefore analyzed. METHOD: Between 9/97 and 10/99 the visualization of orofacial
      tumours in 243 patients by 3D-US was examined, classified on a five-point scale
      and compared to the corresponding CT and MRI scans. RESULTS: Complete
      visualization of the tumours was possible in 85.6 % by 3D-US, whereas the rates
      of MRI and CT were lower with 77.4 % and 61.3 % respectively, mainly because of
      artifacts. The best combinations of methods, 3D-US + CT (96.7 %) and 3D-US + MRI
      (95.1 %) gave almost equivalent results, whereas CT + MRI (83.5 %) was inferior.
      In 2.5 % of the cases none of the methods produced adequate results. CONCLUSION:
      By free selection of sectional planes and direct correlation to the clinical
      findings 3D-ultrasound can improve staging, therapy planning and follow-up of
      orofacial tumours, especially in the case of small tumour size, dental
      crowns/inlays, metal implants or contraindications to MRI.

PMID- 11961724
TI  - The twin-twin transfusion syndrome - an unsolved problem.
AB  - AIM: We analysed the data of pregnancies with twin-twin transfusion syndrome
      (TTTS) in order to identify clinical factors present at the time of diagnosis
      which can be used to predict the outcome of the pregnancy. METHOD: We report
      prenatal sonographic findings, interventions and outcomes of 28 TTTS pregnancies
      over a three-year period. Patients were classified into stages of TTTS as
      follows: Stage I: bladder of donor visible, normal Doppler studies; Stage II:
      bladder of donor not visible, normal Doppler studies; Stage III: abnormal Doppler
      studies; Stage IV: hydrops. RESULTS: In nine pregnancies the infants did not
      survive the perinatal period (the first 28 days after delivery): the median
      gestational age at delivery was 24 (range 21 - 29) weeks; six of these nine
      pregnancies (66 %) were classified as stages III or IV. In five pregnancies one
      infant survived the perinatal period: the median gestational age at delivery was
      28 (range 27 - 32) weeks; four of these five pregnancies (80 %) were classified
      as stages III or IV. In 14 pregnancies both infants survived the perinatal
      period: the median gestational age at delivery was 30.5 (range 28 - 39) weeks;
      two of these 14 pregnancies (14 %) were classified as stages III or IV.
      CONCLUSION: In pregnancies complicated by TTTS, the results of Doppler studies at
      the time of diagnosis represent the most important clinical factor predicting the
      outcome of the pregnancy. At the time of delivery, however, the predicted outcome
      is most directly linked to the gestational age.

PMID- 11961725
TI  - [Intraoperative spinal sonography].
AB  - AIM: Our intention was to examine the value of ultrasonography in the case of
      spinal stenosis caused by bony fragments or a tumour. Pre- and postoperative
      computed tomographies were compared with intraoperative ultrasound images.
      METHOD: Intraoperative sonography during spinal surgery was used after laminotomy
      or laminectomy in twenty patients with a stenosis of the spinal canal, caused by
      fragments or tumours. RESULTS: The posterior vertebral wall as well as tumour
      tissue and myelon can be well distinguished by sonography. The dural sheath
      remains sonographically visible as a white line between tumour-tissue and myelon
      even in the case of immense compression. Small bony fragments or herniated disc
      material are also visible in the spinal canal. Thin surgical instruments can be
      guided into their target region under ultrasonographic control. When the restored
      epidural space can be demonstrated sonographically, this proves complete
      decompression of the spinal cord. CONCLUSION: Intraoperative ultrasound is an
      unrestricted repeatable real-time method for the surgeon to control the
      restoration and the width of the spinal canal. The extent of the operation
      depends on the results of the intraoperative sonography.

PMID- 11961726
TI  - [Complication rates of invasive intrauterine procedures in a centre for prenatal
      diagnosis and therapy].
AB  - AIM: A retrospective analysis of all complications occurring after invasive
      prenatal procedures was performed in order to have exact data for patient
      information and quality control in our department. METHOD: During a period of two
      years 2256 invasive ultrasound-guided procedures were performed. With the help of
      a computer data base, the follow-up of 2066 patients was possible. We
      retrospectively investigated all cases of severe complications resulting in
      intrauterine foetal death or abortion within 14 days after the invasive
      procedure. RESULTS: Depending on the method of invasive testing there were
      different rates of severe complications in single pregnancies, which varied from
      0.44 % up to 0.99 % (Amniocentesis [AC]): 0.74 %, late placental biopsy: 0.44 %,
      chorionic villi sampling: 0.99 %, cordocentesis: 0.75 %. The complication rate
      after AC was 1.49 % in younger, inexperienced colleagues compared to 0.58 % in
      specialists for prenatal medicine. The complication rate in twin pregnancies (AC)
      was 1.99 %. CONCLUSION: Before invasive prenatal procedures can be performed,
      detailed information has to be given to the patients. The exact rate of
      complications should be included in this information. More complicated invasive
      procedures should be centralized in a tertiary centre for prenatal medicine
      because wider experience of the investigators leads to a decreased rate of severe
      complications.

PMID- 11961727
TI  - [Automated quality control of diagnostic ultrasound appliances].

PMID- 11961728
TI  - Dandy-Walker malformation as sonographic marker for fetal triploidy.
AB  - Fetal triploidy is a frequent reason for early abortion, and only few fetuses
      survive into the second trimester of pregnancy. Common sonographic markers for
      triploidy in the second trimester are severe asymmetric growth restriction
      (triploidy of maternal origin) and partial molar changes of the placenta
      (triploidy of paternal origin), together with structural fetal malformations. We
      report prenatal sonographic findings of thirteen triploid fetuses between 18 and
      34 weeks' gestational age (eleven fetuses with 69, XXX, and two fetuses with 69,
      XXY). Intrauterine growth restriction (11/13 fetuses), oligohydramnios (8/13),
      bilateral cerebral ventriculomegaly (6/13), structural heart defects (4/13), and
      Dandy-Walker malformation or Dandy-Walker variant (4/13) were the most frequent
      findings. We conclude that the Dandy-Walker malformation and Dandy-Walker variant
      should be considered as additional sonographic markers for fetal triploidy.

PMID- 11961729
TI  - Chances and shortcomins of adenovirus-mediated ATP7B gene transfer in Wilson
      disease: proof of principle demonstrated in a pilot study with LEC rats.
AB  - BACKGROUND & AIMS: Wilson disease (WD) is an autosomal recessively inherited
      copper storage disease due to mutations in the ATP7B gene. It results in impaired
      biliary copper excretion followed by liver injury leading to cirrhosis. In
      parallel, copper accumulates in other tissues e. g. basal ganglia of the brain
      inducing motoric disorders. Phenotypical cure of Wilson disease by liver
      transplantation raised the question whether gene therapy may represent a
      successful alternative treatment procedure. To examine the principle feasibility
      of this approach we investigated the effects of gene transfer using an adenoviral
      vector construct expressing the human ATP7B cDNA in an established rodent model
      for WD, the Long-Evans Cinnemon rat (LEC). METHODS: Transduction efficiency was
      assessed by RT-PCR, Western blot and immunofluorescence analysis. The therapeutic
      effect was estimated by analyzing holoceruloplasmin and its ferroxidase activity
      in serum, and the copper content of excrements. Changes in copper homeostasis
      were determined by positron emission tomography (PET). RESULTS: Successful, but
      temporary gene transfer was clearly detectable on RNA and protein levels. In
      parallel the temporary therapeutic effect was documented by restoration of serum
      holoceruloplasmin and of its ferroxidase activity. Additionally the Ad-ATP7B
      treated LEC rat revealed a higher (64)Cu content in stool. PET was able to
      visualize differences in (64)Cu distribution between wild type and LEC rats,
      indicating its principle usefulness as analytical tool. CONCLUSION: The data
      demonstrate proof of principle of successful gene therapy in an experimental
      model of WD. As a consequence of successful but only transient therapeutic effect
      of adenoviral gene transfer we can now focus more efficient and permanent gene
      transfer strategies.

PMID- 11961730
TI  - [Cost measurement based on a cost diary in patients with inflammatory bowel
      disease].
AB  - OBJECTIVE: Cost diaries administered by patients have been used as a method to
      measure costs for different diseases. Our aim was to test the application of a
      patient cost diary in patients with inflammatory bowel disease (IBD) and to
      measure disease specific resource utilization and costs. PATIENTS AND METHODS: A
      specific patient cost diary for IBD was developed and tested in a prospective
      pilot study. 105 outpatients with IBD of a University Hospital agreed to
      participate over a 4 week follow-up period. They were asked to report weekly
      their use of medical care and costs related to their illness. Visits to health
      care providers, hospitalizations, drug use, costs due to absence from paid and
      unpaid work, travel costs as well as out-of-pocket expenses were considered.
      RESULTS: The response rate was 90 %. Almost 70 % of the patients estimated the
      diary as easy to fill in. Compared with other data sources, the cost measurement
      using the cost diary showed good agreement regarding costs of drug therapy and
      outpatient hospital treatment. Mean costs due to illness were estimated to be
      1,500 Euro per 4 weeks. This corresponds to total costs of about 20,000 Euro per
      year of care. 69 % of total costs were indirect costs due to illness-related
      absence from work, days of inactivity at home, and early retirement. Direct
      health care and direct non health care costs (e. g. travel costs) were
      responsible for 27 % and 4 % of costs, respectively. DISCUSSION AND CONCLUSION:
      The presented instrument offers a suitable and practical method of assessing IBD
      related resource utilization. The prospectively obtained data for direct medical
      and non medical, as well as indirect costs allow a cost measurement from the
      societal perspective. The presented cost diary can be used for measuring costs
      for economic evaluations of medical interventions.

PMID- 11961731
TI  - Expression of CD44v6 has no prognostic value in patients with colorectal cancer.
AB  - BACKGROUND AND AIMS: In colorectal cancer patients' mortality is largely
      influenced by spreading of tumour cells from the primary tumour site and
      subsequent metastasis formation. CD44 is an adhesion molecule and represents a
      highly variable family of isoforms. The isoform CD44v6 has been associated with
      metastatic spread and poor prognosis in animal models and several human cancers.
      Results of immunohistological studies in primary colorectal cancer are mostly
      retrospective and contradictory. The aim of our prospective study was to assess
      the controversial role of CD44v6 as a prognostic factor in colorectal cancer.
      METHODS: In 93 patients we analysed tumour CD44v6 expression in prospectively
      sampled stage I-IV colorectal adenocarcinomas using RT-PCR and Southern blotting.
      The prognostic value of the CD44v6 expression was assessed using univariate and
      multivariate analysis. RESULTS: CD44v6 expression was found in 47 % of the cases.
      CD44v6 expression failed to show any association with the clinical or
      histological variables examined. CD44v6 expression did not correlate with
      survival in long-term follow-up. The most important prognostic factor in this
      cohort was tumour stage. CONCLUSIONS: Changes in CD446 expression level do not
      predict tumour spread or patient survival in colorectal cancer.

PMID- 11961732
TI  - [Differential diagnosis of frequent pancreatic tumours with echo-enhanced power
      Doppler sonography - presentation of case reports].
AB  - The echo-enhanced Power-Doppler sonography is useful for the differential
      diagnosis of pancreatic tumours. Tumour criteria for the differentiation of
      pancreatic tumours with this procedure are explained using selected cases in the
      present publication. Ductal carcinomas are often hypovascularised compared with
      the surrounding tissue. On the other hand, neuroendocrine tumours are
      hypervascularised lesions. Tumours associated with pancreatitis have a different
      vascularisation pattern depending on inflammation and necrosis. Cystadenomas
      frequently show many vessels along the fibrotic strands. CONCLUSIONS: Pancreatic
      tumours have different vascularisation patterns in the echo-enhanced Power
      Doppler sonography. These characteristics can be used for the differential
      diagnosis.

PMID- 11961733
TI  - [Long-term management of anemia in chronic inflammatory bowel disease].
AB  - The development of a stepwise therapy, as detailed below, can be administered to
      the mostly young patients with Crohn's disease and ulcerative colitis on an out
      patient basis and appropriate to their needs. This is true not only for the
      activity of the disease, but also for extraintestinal manifestations. The
      numerous variations in the stepwise anti-inflammatory therapy of chronic
      inflammatory bowel disease, but also in the substitution therapy of deficiency
      states and the therapy of accompanying extraintestinal diseases provide the
      gastroenterologist with the possibility of a long-term treatment tailored to the
      needs of the individual patient.

PMID- 11961734
TI  - [Hemochromatosis or hemosiderosis? Initial misinterpretation of clinical symptoms
      and laboratory findings in a 62-year-old patient].
AB  - The exact differential diagnosis of iron overload syndromes is mandatory as
      important therapeutic consequences may derive from a correct diagnosis,
      especially when hemochromatosis is present. To facilitate diagnostic and
      therapeutic decisions algorithms and probabilistic calculations based on
      different frequencies of clinical symptoms and typical laboratory findings of the
      diseases in question have been proposed. Overestimation and/or underestimation of
      clinical symptoms and/or laboratory findings in using such calculations, however,
      may lead to incorrect diagnosis and therapy as demonstrated in this case. We
      report on a 62-year-old patient with arthralgia, pathologic glucose metabolism,
      brown skin pigmentation and excessively elevated ferritin and transferrin
      saturation levels, which initially were interpreted as signs of the assumed
      underlying disease (hemo-chromatosis) based on a high initial suspicion level and
      further corroborated by Bayesian probability analysis yielding a probability 99.0
      % for the presence of hemochromatosis. Because of this high probability and the
      patient's wish for treatment phlebotomy was started, but stopped after having
      obtained negative results of genetic testing and normal quantitative liver iron
      values. The diagnosis of hemochromatosis had to be revised and symptoms and
      laboratory findings of this patient were found to be compatible with chronic
      fatty liver and pathologically altered iron metabolism due to chronic alcohol
      intake which the patient has initially concealed. The joint pain was explained in
      terms of chronic degenerative bone destruction, the impaired glucose tolerance
      seen as the consequence of obesity and the skin pigmentation was ascribed to sun
      exposure due to the patient's outdoor activities as a hobby farmer not evaluated
      during initial presentation. The implications and importance of unbiased history
      taking, critical interpretation of clinical symptoms and laboratory findings in
      using probabilistic calculations and diagnostic decision analysis are emphasized
      and the different mechanisms of iron metabolism in hemochromatosis and
      hemosiderosis are discussed.

PMID- 11961735
TI  - Recurrent pseudomembranous colitis as a cause of recurrent severe sepsis.
AB  - Clostridium difficile (C. difficile) colitis accounts for nearly 15-20 % of
      antibiotic-associated diarrhea. Manifestations include asymptomatic carriage,
      self-limited diarrhea, and pseudomembranous colitis, which is sometimes life
      threatening. Despite effective therapy with metronidazole and vancomycin relapse
      rates are 15-33 %. Although colitis is seen in critically ill patients treated
      with combinations of broad-spectrum antibiotics, reports describing severe sepsis
      as a result of C. difficile infection are limited. We describe the case of
      recurrent severe sepsis due to recurrent local intestinal C. difficile infection
      as the only identifiable etiology. The mechanism of severe sepsis may be a
      derangement of the gastrointestinal barrier function. This could result in
      absorption of microbes or endotoxin or activation of inflammatory cascades in the
      submucosa of the intestine or liver. In general, for successful treatment of C.
      difficile infections other than anticlostridial antibiotics should be
      discontinued. However, in the present case bacterial translocation from the
      intestine is an attractive explanation for severe sepsis and therefore additional
      antibiotics had been administered.

PMID- 11961737
TI  - [Diagnosis of pancreatic carcinoma with CT, EUS, MRCP, PET. What is best?].

PMID- 11961739
TI  - Workplace affairs. What happens when life imitates art?

PMID- 11961736
TI  - Heterotopic pancreatitis: gastric outlet obstruction due to an intramural
      pseudocyst and hamartoma.
AB  - Heterotopic pancreas, usually a silent gastrointestinal malformation, may become
      clinically evident when complicated by chronic inflammation. We report a case of
      pancreatitis and extensive pseudocyst formation in the gastric antrum, which
      caused gastric outlet obstruction. The diagnosis was obscured by a history of
      emesis during pregnancy and a previously resected gastric polyp. The nature of
      the obstructive lesion was not diagnosed preoperatively in spite of
      endosonographic evaluation. Intraoperatively, a cystic tumor of the stomach wall
      was found, the lesion was excised, and a pyloroplasty was performed to close the
      excision site. Histology revealed heterotopic pancreatic tissue with chronic
      inflammation, fibrosis and pseudocyst formation and adjacent to this lesion a
      myoglandular hamartoma. The patient is symptom-free two years after surgery and
      no recurrence was found. The nature of heterotopic pancreatic tissue, its
      diagnosis and management are discussed.

PMID- 11961741
TI  - Is it time to scrap doctors and nurses?

PMID- 11961742
TI  - Cutting up rough over wannabe amputees.

PMID- 11961744
TI  - Health care assistants. Unknown factor.

PMID- 11961745
TI  - When should we complain about our colleagues?

PMID- 11961746
TI  - The odd one out.

PMID- 11961747
TI  - Help at hand for people dealing with prion disease.

PMID- 11961749
TI  - Demystifying the mental health service.

PMID- 11961751
TI  - Resuscitation and clinical governance.

PMID- 11961750
TI  - Cross infection of Creutzfeldt-Jakob disease.

PMID- 11961752
TI  - Make your experience work. Models of supervision. Part 3.

PMID- 11961753
TI  - Priming an infusion set--1.

PMID- 11961754
TI  - Sex in the city.

PMID- 11961756
TI  - Adaptation courses. Adaptor plug.

PMID- 11961757
TI  - Bank nurse pay. Bank holiday blues.

PMID- 11961758
TI  - Chechnya. Nurse witness to Russia's dirty war.

PMID- 11961760
TI  - Minority communities. NHS 'drastically failing' in London.

PMID- 11961761
TI  - Is there a great divide between nursing theory and practice?

PMID- 11961762
TI  - Watch out, this is going to be big.

PMID- 11961769
TI  - Danger money.

PMID- 11961770
TI  - All I want is a room somewhere.

PMID- 11961771
TI  - A patient confides that she was awake throughout surgery but doesn't want to be
      labelled a troublemaker. Should I tell?

PMID- 11961772
TI  - If the price is not right, nurse consultant posts will soon be dismissed as hype.

PMID- 11961773
TI  - An isolated problem.

PMID- 11961774
TI  - All you need is a little respect.

PMID- 11961775
TI  - Complications of type 2 diabetes: renal disease and the promotion of patient self
      management.

PMID- 11961777
TI  - Managing postoperative pain: improved epidural infusion.

PMID- 11961776
TI  - Ectopic pregnancy: care on the gynaecology ward.

PMID- 11961778
TI  - Managing transition: 2.

PMID- 11961779
TI  - Reading central venous pressure--1.

PMID- 11961780
TI  - Meeting of minds.

PMID- 11961783
TI  - Bereaved family's fury at prison care.

PMID- 11961785
TI  - Call of the mild.

PMID- 11961786
TI  - Learning from Lexie.

PMID- 11961787
TI  - The dark end of the street.

PMID- 11961788
TI  - Cheap and cheerful.

PMID- 11961789
TI  - What is the care standards bill?

PMID- 11961791
TI  - Did the NHS overestimate the risk posed by the millennium bug?

PMID- 11961792
TI  - New millennium, same old story--the NHS stretched to breaking point by 'winter
      pressures'.

PMID- 11961793
TI  - Illness belongs to the people.

PMID- 11961794
TI  - Gateway to mental health.

PMID- 11961795
TI  - Eye care. Burn marks.

PMID- 11961796
TI  - Oh, what a lovely stoma.

PMID- 11961797
TI  - NT/3M National Nursing awards. Catch-all solution.

PMID- 11961802
TI  - Special food supplements for infants are exactly that--special.

PMID- 11961803
TI  - Working out a strategy for evidence-based practice.
AB  - This paper examines the implications of the nursing strategy Making a Difference
      for patients and health care organizations in achieving and maintaining evidence
      based nursing within clinical governance.

PMID- 11961804
TI  - Practice makes perfect.

PMID- 11961805
TI  - Brief but to the point.

PMID- 11961806
TI  - Deskilling or extending?

PMID- 11961807
TI  - Management guidelines for erectile dysfunction.

PMID- 11961808
TI  - Divided priorities: mental health referrals.

PMID- 11961810
TI  - Skin care. Over exposed.

PMID- 11961809
TI  - Skin care. Are you up to scratch?

PMID- 11961814
TI  - Pressure group warns of London fluoride threat.

PMID- 11961815
TI  - . Nursing research unit to face Parliamentary scrutiny.

PMID- 11961817
TI  - Breast-feeding. Help for mums who bottle out.

PMID- 11961818
TI  - Resuscitation. Shock study triggers call to ban ageist slurs.

PMID- 11961819
TI  - What is the Human Rights Act 1998?

PMID- 11961820
TI  - Is there such a thing as a personality disorder?

PMID- 11961826
TI  - SENs should be cherished not bullied.

PMID- 11961827
TI  - Slippery propaganda.

PMID- 11961828
TI  - Bullied to death.

PMID- 11961829
TI  - Survival and resistance.

PMID- 11961830
TI  - Street wise. Interview by Kristen Downer.

PMID- 11961831
TI  - Managers often turn a blind eye to bullies. Don't let them get away with it.

PMID- 11961832
TI  - I've been told I have to move to another part of the unit, but I don't want to
      go. What doI do?

PMID- 11961833
TI  - Standard bearers.

PMID- 11961834
TI  - The ward hostess: a quality initiative.

PMID- 11961835
TI  - A care pathway for home parenteral nutrition.

PMID- 11961838
TI  - Miscarriage: causes and nursing care.

PMID- 11961839
TI  - Managing your time. Part 3.

PMID- 11961840
TI  - Reading central venous pressure--2.

PMID- 11961848
TI  - Post-traumatic stress disorder. Wounds that don't heal.

PMID- 11961849
TI  - Oncology nurses keep up with exciting trends in blood and marrow transplantation.

PMID- 11961850
TI  - NCI issues statement on mammography screening; ONS responds.

PMID- 11961852
TI  - The knowledge and practice on malaria among community members in Zimbabwe.
AB  - OBJECTIVES: To assess the knowledge of the cause, preventive measures and
      symptoms of malaria, treatment seeking behaviour on malaria and source of
      information about malaria among community members for the planning of effective
      malaria intervention. DESIGN: A cross sectional study was carried out using a
      questionnaire, which was administered by health workers from rural health
      centres. SETTING: Households in rural areas from five districts namely Uzumba
      Maramba Pfungwe (UMP), Hurungwe, Mount Darwin, Bulilimamangwe and Chipinge in
      Zimbabwe. SUBJECTS: 2,531 community members who were in charge of households
      sampled systematically in the area. MAIN OUTCOME MEASURES: Percentage of
      knowledge of transmission, signs and symptoms, prevention methods such as
      residual house spraying and personal protection, and treatment seeking practice
      on malaria. RESULTS: Knowledge of malaria transmission was generally high ranging
      from 57.9% to 95.9%, although there were some misconceptions such as drinking
      dirty water and poor hygiene. Knowledge of malaria preventive methods was varied
      among districts ranging from 19.4% to 93.0% about residual house spraying, and
      low (0.2% to 22.7%), (8.1% to 24.5%) about mosquito nets and repellents,
      respectively. Knowledge of malaria signs was generally high although this also
      varied among districts. Treatment seeking practice on malaria shows that the
      majority of respondents (85.4%) visit the clinic first when seeking treatment
      although there are other options such as shops and traditional healers. Other
      sources of information about malaria mentioned were, health workers (72.9%),
      radio (44.0%), television (37.5%), teachers (25.0%) and village community workers
      (10.0%). CONCLUSION: Despite widespread knowledge about the cause of malaria and
      symptoms, and the fairly extensive sources of health information, understanding
      of the preventive measures was relatively low. Appropriate health education is
      essential to stimulate changes in both knowledge and behaviour in malaria control
      activities. Schools can be effective health education tools as well as health
      facilities.

PMID- 11961851
TI  - Comparative evaluation and assessment of the diagnostic usefulness of four
      commercial HIV-1/HIV-2 antibody assays using two well-characterized serum panels
      from Blood Transfusion Service and the National Health Laboratory Services in
      Zimbabwe.
AB  - OBJECTIVE: To evaluate four Enzyme Linked Immunosorbent Assay (ELISA) HIV kits
      for possible use as a combination at the National Health Laboratory Services
      (NHLS) in Zimbabwe. DESIGN: Laboratory evaluation, sensitivity, specificity and
      cost effectiveness of HIV diagnostic kits. SETTING: Blood Transfusion Service
      (BTS) and Parirenyatwa Hospital in Zimbabwe. SUBJECTS: A total of 346 samples
      from 245 patients referred to Parirenyatwa Hospital and 101 blood donors at BTS.
      MAIN OUTCOME: The main goal was to come out with the best combination of ELISA
      kits in terms of sensitivity, specificity and cost effectiveness for use in
      diagnosis of HIV infection in Zimbabwe. RESULTS: The best combination kit was the
      Murex/Innotest with 100% sensitivity and 98.9% specificity, being slightly
      superior to the Genelavia/Vironostika combination kits in current use at NHLS. In
      addition, the Murex/Innotest combination has the shortest assay running time and
      requires fewer internal controls thereby increasing the number of test specimens
      per run. CONCLUSION: We recommend the use of the Murex/Innotest kits as a
      suitable combination for HIV infection diagnosis in Zimbabwe. The combination has
      a relatively low number of discordant results, drastically reducing the cost of
      running a third confirmatory test to resolve the discordant results. Most
      importantly, this combination maximizes HIV infection diagnosis by its ability to
      detect antibodies to HIV-1 groups M and O as well as HIV-2.

PMID- 11961854
TI  - In vivo drug resistance during treatment for typhoid fever: a case report.
AB  - A case of a 27 year old male who developed resistance to some previously
      sensitive antibiotics while still on treatment for salmonella typhi infection is
      presented. The possible mechanism for such a drug resistance is discussed.

PMID- 11961855
TI  - Supernumerary teeth: literature review.
AB  - A review of the literature on supernumerary teeth in general and supernumerary
      molars in particular was carried out on prevalence, aetiology, complications and
      the treatment of supernumerary teeth. Additional teeth are relatively common and
      are usually of simple conical shape (supernumerary teeth) but may resemble teeth
      of the normal size and shape. The aim of this review is to provide reference
      material for dental practitioners in Zimbabwe.

PMID- 11961853
TI  - Ethosuximide induced lymphadenopathy--a case report.
AB  - A wide range of adverse effects has been reported following prolonged use of
      anticonvulsant drugs. More commonly reported adverse effects for ethosuximide
      include gastric disturbances, psychiatric disorders and Systemic Lupus
      Erythematosus (SLE). Rare instances of leukopenia and pancytopenia have been
      noted. A case is presented of a 12 year old girl who developed generalized
      lymphadenopathy with progressive weight loss and leukopenia following prolonged
      use of ethosuximide for simple absence seizures. The enlarged lymph nodes
      regressed with withdrawal of the drug but re-appeared when the drug was
      recommenced. Sodium valproate was then introduced and ethosuximide discontinued.
      The seizures were successfully controlled with sodium valproate. Histopathology
      report of the lymphnode biopsy showed marked reactive lymphnode hyperplasia.

PMID- 11961856
TI  - Is antenatal antibody screening worthwhile in the Zimbabwean population?

PMID- 11961858
TI  - The reliability of the Shona version of the EQ-5D.
AB  - BACKGROUND: There is an increasing need to have locally applicable health related
      quality of life outcome measures that are both reliable and valid. The aim of
      this paper was to present the Shona version of a Health Related Quality of Life
      Measure, the EQ-5D (Euro Quality of Life--5 Dimensions) and to examine the
      reliability and validity of the translated instrument. METHOD: Thirty eight test
      retest responses from randomly selected members of a high density suburb in
      Harare were analysed. The measures of agreement (Kappa statistic) between the two
      sets of scores were very high and ranged from 0.78 to 1.00 for different domains
      of activity. The correlation between the two sets of scores in the section of the
      instrument that calls for valuation of health state on a visual analogue scale
      (VAS) was high (Spearman's rho = 0.793). It is suggested that, based on this
      small sample, the EQ-5D is a reliable measure of HRQoL and can be utilised in
      studies in a high density Shona speaking population.

PMID- 11961859
TI  - Determinants of reproductive tract infections among asymptomatic women in Harare,
      Zimbabwe.
AB  - OBJECTIVES: To determine the prevalence of and risk factors for reproductive
      tract infections (RTI) among asymptomatic women attending primary health care
      clinics in Harare, Zimbabwe. DESIGN: A cross sectional study. MAIN OUTCOME
      MEASURES: Prevalent RTI, HIV and socio-demographic data. SETTING: Two primary
      health care clinics in Harare. SUBJECTS: 393 consecutive, consenting women aged
      15 to 49 years, presenting at the clinics for antenatal care, family planning, or
      bringing their children to attend preventive care clinics. RESULTS: More than
      half of the women had at least one ongoing RTI. Voluntary reporting of symptoms
      was almost non-existent. Prevalence of HIV was 29.3% and that of classical STIs
      was 15.4% Trichomoniasis vaginalis, 3.9% syphilis, 3.9% Chlamydia trachomatis and
      1.8% Neisseria gonorrhoea. Bacteria vaginosis was diagnosed in 30.3% of the women
      and candidiasis in 25.4%. Presence of any RTI was significantly associated with
      lower level of education, sexual debut < 20 years, a non-monogamous partner, and
      use of a condom during the last sexual encounter. Independent factors associated
      with cervical infections were young age (< 20 years), being unmarried, current
      dysuria, warts, clinical signs of purulent or yellowish discharge, lower
      abdominal pain and cervical friability. Vaginitis was associated with sexual
      debut or marriage < 20 years, a partner who was a frequent traveller, history of
      STI, and presence of abnormal vaginal discharge. CONCLUSION: In view of the high
      prevalence of RTI and HIV and the low reporting of symptoms by infected women, it
      is recommended that strategies that improve women's awareness of urogenital
      symptoms be adopted, along with pro-active inquiry of genital symptoms by the
      health care workers, and treatment of RTIs, in order to reduce the unnecessary
      burden of RTIs.

PMID- 11961860
TI  - Enumeration of CD4 and CD8 T-cells in HIV infection in Zimbabwe using a manual
      immunocytochemical method.
AB  - OBJECTIVES: To enumerate CD4 and CD8 T-cells using the simple and cheap immuno
      alkaline phosphatase (IA) method and to compare it with flow cytometry (FC); and
      to study the effects of duration of sample storage on the IA method results.
      DESIGN: Method comparison study. SETTING: Blair Research Laboratory, Harare,
      Zimbabwe. SUBJECTS: 41 HIV positive and 11 HIV negative men and women from Harare
      participating in HIV studies at Blair Research Laboratory, Zimbabwe. MAIN OUTCOME
      MEASURES: CD4 and CD8 T-cell counts by FC and the IA method. RESULTS: The IA
      method and FC were highly correlated for CD4 counts (Spearman rs = 0.91), CD4
      percentage (rs = 0.84), CD8 count (rs = 0.83), CD8 percentage (rs = 0.96) and
      CD4/CD8 ratio (rs = 0.89). However, CD4 cell counts and percentage measured by
      the IA method were (mean difference +/- SE) 133 +/- 24 cells/microL [corrected]
      and 6.7 +/- 1.1% higher than those measured by the FC method (p < 0.0001)
      respectively. CD8 counts and percentages by the IA method were lower than those
      by the FC method (p < 0.01). Accordingly, the IA method gave a higher CD4/CD8
      ratio (p < 0.01). IA method CD4 counts < 300/mL best predicted FC CD4 counts <
      200/mL while IA CD4% < 25 best predicted FC CD4% < 14%. IA method CD4/CD8 ratio <
      0.8 best predicted FC CD4/CD8 ratio < 0.5. Smears stored for up to 18 months gave
      results similar to fresh smears. CONCLUSION: The IA method correlates well with
      but gives CD4 counts and percentages that are higher than those determined by FC.
      On the contrary, the IA method gives CD8 counts and percentage that are lower
      than FC values. The method is a cheap and reliable alternative to FC and allows
      storage of samples for extended periods before analysis, making it an appropriate
      technology for resource poor countries.

PMID- 11961861
TI  - Post operative pain therapy: a survey of prescribing patterns and adequacy of
      analgesia in Ibadan, Nigeria.
AB  - OBJECTIVE: To establish prescribing patterns for post operative pain therapy,
      it's adequacy, as well as patients' satisfaction with the prescriptions. DESIGN:
      A survey of doctors' prescriptions for post operative pain therapy over a six
      month period. SETTING: The University College Hospital Ibadan, Nigeria, the
      oldest teaching hospital in the country. SUBJECTS: All consecutive adult elective
      general surgical patients operated on over a six month period, who were on
      admission for at least 72 hours after surgery. Patients with prolonged post
      operative unconsciousness or those unwilling to answer the questionnaire were
      excluded. INTERVENTION: The anaesthetic charts, recovery room and treatment sheet
      were reviewed to complete a structured, pretested and precoded questionnaire. Two
      other questionnaires were administered to patients at 24 and 48 hours post
      operatively to review the effect of the analgesic prescribed. RESULTS: 149
      patients met the inclusion criteria. Moderate to unbearable pain was reported in
      68.7% of the patients at 24 hours and 51.7% of patients by 48 hours. Post
      operative analgesics were to be given via only the intramuscular route in all
      cases. There was a limited range of drugs to choose from; pethidine, pentazocine
      and dipyrone were the only drugs available. Pethidine was prescribed four hourly
      in 2.7%, six hourly in 46.9% and eight hourly in 25.9%, of the cases. Eighty five
      percent of the patients who were given dipyrone complained of moderate to
      unbearable pain post operatively. Inadequate doses of analgesics were generally
      given. Despite the high incidence of pain, 63.9% of patients still reported that
      they were very satisfied with their pain relief. CONCLUSION: Prescription
      patterns for post operative pain relief have not changed to include many of the
      new methods presently available. Only one route of administration is still used
      for a limited range of opioid and non-opioid drugs. Patients still experience a
      high incidence of moderate to unbearable pain in the post operative period. This
      can be improved by prescribing drugs at shorter intervals to reflect their
      pharmacokinetics and using newer techniques of drug administration.

PMID- 11961862
TI  - Prediction of peak expiratory flow rates in stunted children.
AB  - OBJECTIVE: To assess the effect of stunting on peak expiratory flow rates (PEFR)
      in Malawian children. DESIGN: Cross sectional study. SETTING: Two public primary
      schools randomly selected in Blantyre, the largest city in Malawi. SUBJECTS: 266
      boys and 273 girls aged six to 14 years. MAIN OUTCOME MEASURES: PEFR, height,
      weight and age of children were determined using standard techniques. Nutritional
      status of children was assessed using WHO/NCHS height for age, weight for age and
      weight for height reference standards. RESULTS: The data of PEFR were analysed by
      regression on age and stature. One hundred children (18.6%) were classified as
      stunted. None of them was under weight or wasted. The equations for prediction of
      PEFR were calculated separately for stunted and non-stunted children. Stature was
      a significant predictor of PEFR values in both groups of children. The
      differences between stunted and non-stunted children of both sexes in slopes and
      intercepts of the regression lines of PEFR on stature were non-significant.
      Stunted children of both sexes had significantly lower PEFR than their
      counterparts with normal height for age index. CONCLUSIONS: Stunting in Malawian
      children aged six to 14 years is associated with decreased rate of development of
      PEFR in proportion to linear growth retardation. Prediction equations calculated
      for children with normal height for age index can be used for assessment of PEFR
      in stunted children.

PMID- 11961864
TI  - Topographical relations of the vertebral arteries in the human neck: an
      anatomical study.

PMID- 11961863
TI  - Superficial brachial artery terminating as radial and superficial ulnar arteries:
      a case report.

PMID- 11961865
TI  - An accurate and timely diagnosis is key for TEN and SJS.

PMID- 11961866
TI  - Ethics in action.

PMID- 11961867
TI  - An alternative to hysterectomy.
AB  - For many women with symptomatic fibroids, hysterectomy has been an undesirable,
      but definitive, treatment for their condition. The good news is that uterine
      artery embolization, a new approach that shrinks fibroids by embolizing their
      blood supply, is proving to be a safe and effective alternative.

PMID- 11961868
TI  - When candida turns deadly.
AB  - Thrush, diaper rash, and vaginal yeast infection are all common manifestations of
      candida. But for the immunocompromised patient, this common fungal species can
      cause a host of problems, including life-threatening infections.

PMID- 11961869
TI  - Bioterrorism.

PMID- 11961870
TI  - Is a legal career for you?
AB  - Your top-notch clinical and communication skills serve you well at the bedside.
      But if you're looking for a change, these same skills can open doors for you in
      the legal arena, as a legal nurse consultant.

PMID- 11961872
TI  - A male RN warns other men to avoid the nursing profession.

PMID- 11961871
TI  - Turn up the volume.

PMID- 11961873
TI  - Onchocerciasis among school children in Kafa, South West Ethiopia.
AB  - A cross-sectional survey was undertaken to determine the magnitude,
      manifestations, and practices related to Onchocerciasis on 1337 students of six
      junior secondary schools of Kafa Zone in January 1993. Information on symptoms of
      the disease and the frequency of common practices that would bring the subjects
      to the breeding sites was collected by interview, while physical measurements and
      clinical examination was used to collect data on visual acuity, nutritional
      status and objective manifestations of the disease. Skin snip from both gluteal
      areas was examined to determine the microfilarial rate and density of infection,
      while nutritional status using Body Mass Index for Age (BMI-for Age), and visual
      impairment following the standard procedures was categorized. The majority, 1179
      (88.2%) of the subjects, were aged 15 years and less of which males constituted
      54.5% (728). The overall microfilarial carrier rate was 15.6% (95% CI = 13.7
      17.6%) while the density of infection was 1.4 mf/mg skin snip. The prevalence and
      density of infection varied significantly among the twelve aggregates of villages
      identified based on the similarity of the ecological feature and contiguity of
      home address of the students. Males had significantly higher rate and density of
      infection but the difference by age was not significant. The prevalence of
      infection was significantly higher among the students who had reported frequent
      bathing, swimming, fishing and collecting firewood at/or near the rivers
      identified as the probable breeding sites of the vector, while there was no
      statistically significant association between infection and washing clothes,
      fetching water or crossing over the rivers. Groin lymph nodes enlargement,
      photophobia and itching were the leading symptoms complained by the infected
      subjects. However, only itching and the objective features related to the
      cutaneous Onchocerciasis were significantly associated to the infection. Visual
      acuity didn't differ among positive and negative subjects. Nutritional status was
      significantly associated with Onchocercal infection. Based on these findings
      recommendations are given on the areas of intervention and further study.

PMID- 11961874
TI  - Chronic suppurative otitis media in a children's hospital in Addis Ababa,
      Ethiopia.
AB  - Our knowledge of chronic suppurative otitis media is scanty in Ethiopia. This
      hospital-based study was, thus, conducted prospectively over a period of 2 years
      among children visiting a tertiary facility in Addis Ababa. Demographic,
      clinical, audiometric and microbiological data were collected using a preformed
      questionnaire. A total of 391 patients constituting 0.6% of the hospital patient
      population and 22.3% of those seen at the ear, nose, and throat clinic had
      chronic suppurative otitis media. Most (82.1%) of them were from Addis Ababa, the
      male to female ratio was 1.6:1, and their median age at presentation was 5.9
      years. Otorrhoea had started before the age of 2 years in 269 (68.8%), was
      bilateral in 215 (55.0%), recurrent in 285 (72.9%), and continuous in 106
      (27.1%). Otalgia was reported in only 18%. Hearing loss was the major presenting
      symptom and the loss was moderate to severe (grades 2 and 3) in 32 (69.6%) and
      slight (grade 1) in 14 (30.4%) of the ears tested audiometrically. Malnutrition,
      nasopharyngitis, measles, HIV infection, tuberculosis, diabetes mellitus,
      neoplastic diseases, and structural abnormalities were common antecedents.
      Serious complications included systemic infections, otogenic meningitis,
      mastoiditis, and tetanus. A total of 106 bacterial isolates were cultured from
      ear discharges of 80 patients. Proteus species were the commonest, accounting for
      40 (37.7%) followed by Staphylococcus aureus, Pseudomonas aeruginosa, and Gram
      negative enterics. All isolates were highly resistant to the commonly used
      antibiotics including penicillin, ampicillin, amoxycillin, trimethoprim
      sulfamethoxazole, and chloramphenicol. Augmentin, gentamicin, and kanamycin were
      the only drugs to which most of the pathogens were sensitive. Marked improvement
      on the discharge was achieved in 64% of the 116 patients who complied with
      treatment. Awareness about the health implications of the disease seemed to be
      lacking in among the caretakers. Selective use of antibiotics and continuous
      aural cleansing need to be promoted. More elaborate epidemiological studies will
      be required to define the magnitude of the problem and identify optimal
      therapeutic modalities of suppurative ear disease in Ethiopia.

PMID- 11961875
TI  - Prevalence of wheeze and asthma related symptoms among school children in Addis
      Ababa, Ethiopia.
AB  - This survey was conducted as part of the international multi-centre study to
      determine the prevalence of wheeze and asthma-related symptoms among school
      children in Addis Ababa, Ethiopia. It was conducted in June 1995. A standardized
      self-administered questionnaire developed by the International Study of Asthma
      and Allergies in Children (ISAAC) was used. The questionnaire was designed to
      offer a standardized epidemiological instrument to ensure comparison of results
      from wide range of countries. A total of 2951 children aged 13 and 14 years were
      enrolled into the study, of which 1393 (47.2%) were males and 1558 (52.8%) were
      females. Five hundred fifty seven children (18.2%) reported that they have had
      wheezing at least once in the last 12 months while only 84 children (2.8%)
      reported to have "Bronchial Asthma". One hundred eighty eight (6.4%) and 214
      (7.3%) children reported sleep disturbance and limitation of speech associated
      with attacks, respectively. Nocturnal cough was reported by 805 (27.3%) children.
      Eight hundred two (27.2%) children reported exercise-induced wheeze. This study
      revealed that the prevalence of wheeze and other asthma related symptoms to be
      fairly high among school children of Addis Ababa, Ethiopia. Moreover, the
      majority of these children do not seem to know their problems and therefore,
      remain untreated. Further studies are recommended to precisely determine the
      prevalence of wheeze and asthma using more objective methods such as bronchial
      hyper-responsiveness test.

PMID- 11961876
TI  - Arterial oxygen saturation in Addis Ababa during diazepam-ketamine anaesthesia.
AB  - Addis Ababa is situated at an altitude of approximately 8500 ft and has a
      barometric pressure of close to 570 mmHg. Arterial blood gas values during the
      administration of anaesthesia with spontaneous ventilation have not been
      extensively studied. During the period January to July 1993, oxygen saturation
      was determined in 46 unpremedicated patients prior to minor surgery. Following
      this, patients received diazepam 0.1-0.2 mg/kg and ketamine 2 mg/kg during which
      a clear airway was maintained and peripheral oximetry was monitored continuously.
      The SpO2 was recorded for each patient at one minute intervals until 5 minutes
      and thence at 7, 10 and 15 minutes. The average SpO2 decreased below 90% at 2, 3
      and 4 minutes and of the 46 patients, 8 (17.3%) required additional oxygen when
      their saturation fell below 80%. It is concluded that airway management and
      supplemental oxygen should be available when using this technique.

PMID- 11961877
TI  - Characteristics of insulin requiring diabetes in rural northern Ethiopia--a
      possible link with malnutrition?
AB  - We have examined 100 consecutive insulin-treated diabetic patients from the
      Diabetic Clinic at Mekelle Hospital in Tigray, Northern Ethiopia; an area of low
      socio-economic status recently affected by severe famine. The study was conducted
      over a six month period (1997). Mean age of onset of diabetes was 27 +/- 10 y
      (SD) and there was a male excess (3.1:1.0). Body Mass index (BMI) at diagnosis
      was very low at 15.8 +/- 2.8. Because of erratic insulin supply 48 (48%) had
      interrupted insulin treatment in the past for a mean duration of 9 +/- 12 weeks
      (range 1-78). Despite this, only 2 (4%) developed ketoacidosis (DKA). The
      patients thus have features suggestive of malnutrition-related diabetes mellitus
      (MRDM) possibly of the "malnutrition-modulated" (MMDM) type in view of the
      apparent absence of overt exocrine pancreatic disease. The famine in this area 10
      years previously may be of relevance to the aetiology of diabetes in these
      patients.

PMID- 11961878
TI  - Peripheral neuropathy following administration of nerve tissue antirabies
      vaccine.
AB  - In 1997, two patients were admitted to Tikur Anbessa Hospital with complaints of
      ascending paralysis in all extremities following administration of sheep brain
      tissue anti-rabies vaccine following a rabies exposure. The paralysis had started
      after 14 daily subcutaneous injections of the Fermi type nerve tissue vaccine.
      After an eight week stay in the hospital with supportive care and physiotherapy,
      the patients showed remarkable improvement. They received a booster dose of
      vaccine while in the hospital, with no deterioration in their neurological status
      and were discharged.

PMID- 11961879
TI  - 24th Kellersberger Memorial lecture, 1999 thalidomide: will the past overshadow a
      promising future?

PMID- 11961880
TI  - Invitational forum on nursing education.

PMID- 11961881
TI  - A survey of advanced practice nursing in Texas. Characteristics and patterns of
      practice.

PMID- 11961882
TI  - The positive side of the nursing shortage.

PMID- 11961883
TI  - Homeland security for nurses in Texas.

PMID- 11961884
TI  - Biotech's new colossus. Move over, Big Pharma. Amgen boasts better growth.

PMID- 11961885
TI  - The socialite scientist.

PMID- 11961886
TI  - Dynamic risk factors: the Kia Marama evaluation.
AB  - Risk assessment is an essential part of clinical practice. Each of the three
      aspects of risk (static, stable, and acute dynamic) are important at various
      points of contact between the man and the systems that are responsible for
      providing service. Dynamic factors, the typical treatment and supervision
      targets, have received less research attention than static factors. This paper
      examined the extent to which pretreatment, posttreatment and change scores were
      associated with reoffending among men incarcerated for sexually molesting. The
      results were generally supportive of change in prooffending attitudes as the key
      to not reoffending and suggested that the perspective-taking component of empathy
      and the use of fantasy may be important mechanisms. Affect scales generally
      failed to show any relationship with reoffending, outside decreases in trait and
      suppressed anger. Moreover, these data suggest that we could improve our
      assessments and treatment through increased sensitivity to offense pathways.

PMID- 11961887
TI  - The relative utility of fixed and variable risk factors in discriminating sexual
      recidivists and nonrecidivists.
AB  - This study compared the relative utility of fixed and variable risk factors in
      discriminating between recidivist and nonrecidivist sexual offenders. Subjects
      were 95 adult male offenders released from the Canadian federal correctional
      system between 1988 and 1992. Risk factors from the Sexual Violence Risk--20 (SVR
      20; D. P. Boer, S. D. Hart, P. R. Kropp, & C. D. Webster, 1997) were coded from
      prerelease institutional records; sexual and nonsexual violent recidivism was
      coded from postrelease police and correctional records. SVR-20 risk factors were
      categorized as fixed (static) or variable (dynamic) markers according to the
      criteria of H. C. Kraemer et al. (1997); the fixed risk markers were further
      divided into offense history and psychosocial factors. Hierarchical Cox
      regression survival analyses were conducted to compare the relative contribution
      of fixed offense history, fixed psychosocial, and variable psychosocial risk
      markers in accounting for any violent recidivism and sexually violent recidivism.
      Analyses indicated that fixed psychosocial factors added little to the models
      comprised fixed offense history factors alone. There was some evidence that
      variable psychosocial factors had incremental validity when added to predictions
      made on the basis of fixed factors, particularly in the prediction of sexual
      violence. The individual factors that were included in the final models are
      consistent with previous findings, and support the use of sexual deviance and
      antisocial lifestyle variables in the prediction of recidivism among sexual
      offenders.

PMID- 11961888
TI  - Constructing and testing a framework for dynamic risk assessment.
AB  - This paper describes the construction and testing of a framework for dynamic risk
      assessment. A review of previous studies identified 4 domains into which dynamic
      risk factors for sexual offending seem to fall. These were sexual interests,
      distorted attitudes, socioaffective functioning, and self-management.
      Psychometric indicators for 3 of the domains were identified, and 2 studies are
      reported using these indicators to test the framework. Study 1 divided men
      serving a prison sentence for a sexual offense against a child into 2 groups-
      those with a previous conviction of this kind (Repeaters) and those for whom this
      was the only time they had been sentenced for such an offense (Current Only). The
      Repeaters were found to show more distorted attitudes, worse socioaffective
      functioning, and poorer self-management than did the Current Only group. Study 2
      used a simple algorithm to combine these psychometric indicators into an overall
      "Deviance" classification. Reconviction data was obtained for offenders
      classified as high, moderate, or low on Deviance. Sexual reconviction was found
      to be monotonically associated with the Deviance classification. Logistic
      regression analysis showed that both static variables (Static-99) and the
      Deviance classification made independent contributions to prediction. It is
      suggested that risk assessment procedures should combine these 2 approaches.

PMID- 11961889
TI  - The relationship between static and dynamic risk factors and reconviction in a
      sample of U.K. child abusers.
AB  - This study examined how well historical information and psychometric data
      predicted sexual recidivism in a sample of child abusers about to undergo group
      based cognitive behavioral treatment in the community. Static, historical
      factors, as measured by the Static-99 (R. K. Hanson & D. Thornton, 2000),
      significantly predicted recidivism over the 6-year follow-up period. High-risk
      men were over 5 times more likely to be reconvicted for a sexual offence compared
      to low-risk men. Adding psychometric measures of dynamic risk (e.g., pro
      offending attitudes, socio-affective problems) significantly increased the
      accuracy of risk prediction beyond the level achieved by the actuarial assessment
      of static factors. This result indicates the importance of considering dynamic
      risk factors in any comprehensive risk protocol.

PMID- 11961890
TI  - First report of the collaborative outcome data project on the effectiveness of
      psychological treatment for sex offenders.
AB  - This meta-analytic review examined the effectiveness of psychological treatment
      for sex offenders by summarizing data from 43 studies (combined n = 9,454).
      Averaged across all studies, the sexual offence recidivism rate was lower for the
      treatment groups (12.3%) than the comparison groups (16.8%, 38 studies,
      unweighted average). A similar pattern was found for general recidivism, although
      the overall rates were predictably higher (treatment 27.9%, comparison 39.2%, 30
      studies). Current treatments (cognitive-behavioral, k = 13; systemic, k = 2) were
      associated with reductions in both sexual recidivism (from 17.4 to 9.9%) and
      general recidivism (from 51 to 32%). Older forms of treatment (operating prior to
      1980) appeared to have little effect. Future directions for improving the quality
      of sex offender treatment outcome evaluations are discussed.

PMID- 11961891
TI  - Introduction to the special section on dynamic risk assessment with sex
      offenders.

PMID- 11961893
TI  - [Pharmaceutical chemistry in a pharmacy practice].
AB  - The authors examine the utility and application of pharmaceutical chemistry is
      taught at the Faculty of Pharmacy, Semmelweis University, in the everyday
      pharmacy practice. Selected examples of the professional chemical knowledge
      necessary in different activities of pharmacists (as in drug quality control,
      storage of medicines, preparation of drugs in pharmacy and their issue
      (expenditure) to the patient etc.) are reviewed. Their experimental work on
      determination of expiry of an "ex tempore" prepared medicine demonstrates that it
      is possible to meet the principles of Good Pharmacy Practice (GPP). The paper is
      based on certain chapters of diploma work of H. B., tutor T. N. K.

PMID- 11961892
TI  - [Use of crystal conversion reactions in the synthesis of pentacyclic alkaloid
      analogues].
AB  - During investigation of substitution of debenzorutaecarpine derivatives thermal
      cyclization reactions was observed to produce new fused heterocyclic systems. The
      optimal temperature of cyclizations was determined by differential calorimetric
      measurements of crystals of intermediate products. The thermolysis of 2-azido-3
      formil-debenzorutaecarpine gave, after elimination nitrogen, izooxazolo
      debenzorutaecarpine in good yield. The cyclization of the 2-azido-3-nitroso
      debenzorutaecarpine readily led to oxadiazolo E-ring analogue of rutaecarpine.
      The thermal cyclization of 2-hydroxy-debenzorutaecarpines gave 2-oxo- and 4-oxo
      pyrano E-ring analogues of rutaecarpine. The structure of substances was
      confirmed by spectroscopic methods. The synthesised compounds are considered as
      first representatives of new heterocyclic ring systems.

PMID- 11961894
TI  - [Biopharmaceutical considerations of dissolution testing used as a prognostic
      tool for oral drug adsorption].
AB  - Drug dissolution is a prerequisite to drug absorption and in vivo effectiveness
      for almost all drugs given in oral solid dosage forms. Drug absorption depends on
      the dissolution and solubilization of the drug under physiological conditions,
      and the permeability across the gastrointestinal tract. Because of the critical
      nature of the first steps, in vitro dissolution may be relevant to the prediction
      of biological response. Dissolution tests are applied to choose between
      formulation factors, assess the lot-to-lot quality of a drug product according to
      the biobatch; and ensure continuing product quality and performance after certain
      changes (e.g. in the formulation and manufacturing process, site of manufacture,
      scale-up). The recently developed Biopharmaceutical Classification System (BCS)
      has several benefits for recognizing how dissolution tests can be designed and
      which physiological factors have to be taken into consideration for the in vitro
      evaluation of solid dosage forms. Choice of test conditions (composition, volume
      and hydrodynamics of dissolution medium) should be based on where the drug is
      best absorbed in the gastrointestinal tract, and on whether it is administered in
      fasted or fed state. Duration of test and physiologically representative media
      can be selected to simulate gastric and intestinal environments according to the
      permeability profile of the drug, but mimicking in vivo hydrodynamics remains
      problematic and further research is required. To provide a basis for predicting
      the likelihood of achieving a successful in vivo-in vitro correlation, this
      review summarizes the biopharmaceutical considerations of in vivo drug release in
      accordance with the BCS.

PMID- 11961895
TI  - [New diterpene polyesters isolated from Hungarian Euphorbia species].
AB  - Sixteen new diterpene polyesters were isolated and identified from Hungarian
      Euphorbiaceae species. Two of them (21, 23) are based on formerly unknown
      diterpene core. The structures of three jatrophane type diterpene heptaester were
      elucidated (1, 3, 6), which are diterpenoids with the highest degree of
      esterification identified from this plant family. Some of the isolated compounds
      have pharmacological effects, others are under testing now.

PMID- 11961896
TI  - [Transdermal therapeutic systems].
AB  - Transdermal therapeutic systems (TTS) gain continuously increasing importance in
      therapy due to their advantageous properties. They assure constant concentration
      of the active substance in the blood, a lower amount of the drug compared to the
      orally administered dose is sufficient, side effects decrease, and the therapy is
      painless. Since the appearance of the first products many TTSs have been
      developed containing a wide variety of active substances including hormonal,
      antihypertensive, antianginal, and analgesic plasters. Nowadays TTSs belong to
      the most advanced formulations. There is ongoing research in the field of
      regulating the active substance release with electric current or ultrasound.
      There are systems containing insulin, cytostatics, antiparkinsonians,
      contraceptives, and anxiolytics under development.

PMID- 11961897
TI  - [Pharmacological models to investigate the role of the adrenergic system on post
      partum rat uterus].
AB  - The adrenergic system plays a major role in the regulation of the pregnant
      uterine contractility. Our aim was to develop an experimental animal model to
      study the role of the alpha 1A-adrenergic receptor (AR) in uterine motor activity
      by antisense oligonucleotides (AONs). AONs were injected with DOTAP and pluronic
      gel into the uterine lumen of post-partum rats 2-3 hours after delivery. The
      decrease of the alpha 1A-AR density by AON was demonstrated by RT-PCR method,
      Western blot analysis and radioligand binding assay on rat uterus preparations 24
      h after delivery. The changes in the contractility of the uterus were measured on
      isolated rat uterine tissue by electric field stimulation (EFS). The EFS
      investigation demonstrated that the effect of the specific alpha 1A-blocker 5
      methylurapidil and WB4101 was significantly decreased in the AON-treated rat
      uterus as compared to the control group but the effect of the beta-mimetic
      terbutalin and alpha 1D-antagonist BMY7378 was unchanged. Our result suggest that
      the alpha 1A-ARs play a very important role in the regulation of uterine
      contractility, and may serve as the basis for a subsequent new group of
      tocolytics (uterus selective alpha 1-antagonists), which may lead to more
      selective therapy than currently used beta-mimetics.

PMID- 11961898
TI  - [The effect of carvedilol on enhanced adp-ribosylation and red blood cell
      membrane damage caused by free radicals].
AB  - OBJECTIVE: Previous studies have reported that the beta and alpha adrenoceptor
      blocker carvedilol had unique protective effect on free radical induced
      myocardial injury. The aim of this study was to examine how carvedilol regulates
      ROI-mediated signaling and decreases RBC membrane damage in heart perfusion and
      rheological model. METHODS: The ischemia-reperfusion induced oxidative cell
      damages, and changes in the intracellular signaling mediated by reactive oxygen
      species and peroxynitrite were studied on rats, in Langendorff heart perfusion
      system (n = 15). The effect of carvedilol on red blood cell suspension viscosity
      (hematocrit: 60%) incubated with free radical generator (phenazine methosulphate)
      was also investigated (n = 10). The measurements were performed on a capillary
      viscosimeter. RESULTS: In both studies a protective effect of carvedilol was
      found, as the decrease of red blood cell suspension viscosity and K+
      concentration in the supernatant indicated. Carvedilol significantly decreased
      the ischemia-reperfusion induced free radical production and the NAD+ catabolism
      and reversed the poly- and mono-ADP-ribosylation. Carvedilol also decreased the
      lipid peroxidation and membrane damages as determined by free malondialdehyde
      production and the release of intracellular enzymes. The self ADP-ribosylation of
      isolated PARP was also significantly inhibited by carvedilol. CONCLUSION: Our
      results show that carvedilol can modulate the ROI-induced signaling through poly-
      and mono-ADP-ribosylation reactions, the NAD+ catabolism in postischemic perfused
      hearts and has a marked scavenger effect on free radical generator induced red
      blood cell membrane damage. All these findings may play an important role in the
      beneficial effects of carvedilol treatment in different cardiovascular diseases.

PMID- 11961899
TI  - [Carotenoid contents of herbal teas].
AB  - Carotenoid composition of 14 herbal tea consumed by Herbaria was investigated by
      HPLC method. The main components were lutein (36-49%) cis-luteins (2-20%) and
      beta-carotene (3-25%). alpha- and beta-cryptoxanthin, alpha-carotene and some 5,6
      epoxy-carotenoids (neoxanthin, violaxanthin, antheraxanthin) were detected. The
      chlorophyll content was also measured.

PMID- 11961900
TI  - [Efficiency of supercritical fluid extraction for the production of non-volatile
      terpenoids from Taraxaci radix].
AB  - Supercritical fluid extraction (SFE) is an extraction technique which exploits
      the solvent properties of fluids above their critical point. As a result
      supercritical fluid extraction was used to gain various active substances from
      plants. The use of SFE to obtain bioactive substances from medicinal plants over
      the past twenty years has been proved to be a viable alternative for the
      extraction of natural compounds. Dandelion (Taraxacum officinale Wiggers et
      Webers, Asteraceae) is one of the best known European medicinal plants, not only
      as a traditional medicine but perspective raw material for modern
      phytopharmaceuticals. From the characteristic principles our attention has been
      directed to triterpenes and phytosterols with anti-inflammatory activity, which
      were extracted with supercritical carbon dioxide. Designed experiments were
      carried out to determine the optimal extraction parameters. The products obtained
      by supercritical fluids extraction were compared to extracts prepared by
      traditional extraction method (Soxhlet) with n-hexane and ethyl alcohol solvents.
      The content of triterpenes and sterols was monitored after saponification by thin
      layer chromatography-densitometry. The products gained by supercritical fluid
      extraction were different from the traditional ones both in their appearance and
      composition. Triterpenes and their esters were extracted quantitatively by
      supercritical fluid extraction using CO2 as solvent and the extraction dynamic
      for triterpenes and phytosterols was different. Triterpenes had a higher
      concentration in the SFE product then in the extracts prepared by traditional
      methods.

PMID- 11961901
TI  - [Comparative study of Glycyrrhiza glabra L. and Glycyrrhiza echinata L. of
      different origin. Medicinal plant polysaccharides III].
AB  - Comparative study was carried out among the polysaccharides of Chinese,
      Lithuanian and Hungarian origin Glycyrrhiza glabra L. as well as the Hungarian
      origin Glycyrrhiza echinata L. Monosaccharide composition, measured as alditol
      acetates, of Chinese and Hungarian G. glabra was very similar, but the Lithuanian
      G. glabra and the G. echinata were quite different. The monosaccharides of
      polysaccharides isolated from root and stem of G. echinata show significant
      differences (Table II.). All investigated samples contain glucuronic acid, the G.
      echinata contains also galacturonic acid (Table II.). Some fractions with higher
      uronic acid content and the acidic polysaccharides isolated from these fractions
      were studied and their monosaccharide composition was determined (Table III. and
      IV.).

PMID- 11961902
TI  - [Preparations of liposomal morphine. Investigation of the interaction of morphine
      and its derivatives with the dipalmitoyl phosphatidylcholine membrane].
AB  - Liposomes composed of the lipids of biological membranes are suitable for drug
      delivery. To reach a better therapeutical effect it is important to know the
      properties of interactions between the drug and lipid molecules. From dipalmitoyl
      phosphatidylcholine (DPPC) using ultrasound small liposomes containing morphine
      were prepared. The amount of entrapped morphine was determined with
      spectrophotometry and luminescence spectroscopy. The interaction between the
      molecules of morphine and its derivates (codeine, N-methyl-morphine, N-methyl
      codeine) and the DPPC lipid was studied with differential scanning calorimetry
      (DSC) and electron spin resonance (ESR) methods. Our studies indicated that the
      molecules of morphine and its derivates principally interact with the environment
      of DPPC lipid head groups. Due to the interaction the mobility of head groups
      decreases especially in case of codeine and N-methylcodeine.

PMID- 11961903
TI  - [Role of analytical chemistry in the pharmacy of the 21st Century].
AB  - After briefly outlining the state-of-the-art of analytical chemistry in general
      at the turn of the century the instrumental techniques and methods currently
      available for drug analysis are described. The role of analytical chemistry in
      pharmacy, pharmaceutical research and pharmaceutical industry is discussed with
      emphasis on the efficacy, safety and economy of drug therapy. Finally some
      thoughts are presented on the possible trends of drug analysis in the forthcoming
      decades.

PMID- 11961904
TI  - [Electroanalytical methods in the European pharmacopoeia].
AB  - A brief survey on the electroanalytical test methods applied by the European
      Pharmacopoeia is presented by the authors. The frequency of the use of
      electrochemical tests and the main fields of their application in the monographs
      together with the trends of development are discussed. Paying a special attention
      to the measures taken by the pharmacopoeia to reduce the systematic and random
      error in each type of measurements, the authors are analysing the content and
      characteristics of texts describing the electrochemical methods. System
      suitability tests included in the different procedures and their efficacy in
      ensuring the criteria established in the validation studies carried out during
      elaboration of the test methods are also shown.

PMID- 11961905
TI  - [Atomic spectrometry methods for the determination of trace metal impurities in
      pharmaceutical substances].
AB  - Direct GFAAS method was developed for determination of traces of platinum metals
      (Pd, Rh) in pharmaceutical substances. The multielement TXRF method with or
      without preconcentration was applied as element specific screening procedure for
      inorganic impurities. It was found that the developed FI-GFAAS method could be
      used for determination of trace metal impurities (Pb, Ni, Co, Cd, Cr(III)) in
      pharmaceutical substances in ng/g levels. The two chromium forms can be separated
      and quantified preconcentrating on IDAEC and anion exchanger (DE cellulose). FI
      GFAAS method was worked out using chelating cellulose (IDAEC, DEN-cellulose, and
      recently synthesised oxime-, and sulphoxine-celluloses) microcolumns for
      preconcentration of palladium. The preconcentration was optimised by species
      distribution curves.

PMID- 11961906
TI  - [Examination of liquid crystalline gel systems containing chlorhexidine on the
      structure and the drug release].
AB  - The aim of the thesis was to examine liquid crystalline gel systems as novel,
      locally applied drug delivery systems. For developing liquid crystalline vehicle,
      different ratio of Synperonic A7--water mixtures was prepared. Chlorhexidine,
      chlorhexidine acetate and chlorhexidine gluconate were used as model drugs.
      Liquid crystalline structure, drug release and drug release kinetic of the
      samples were studied at increasing surfactant concentration and the effect of the
      different drugs on the physicochemical properties of the samples and on the
      membrane transport was examined. For the analysis of the prepared liquid
      crystalline systems polarising microscopy, rheology test, differential scanning
      calorimetry, small-angle neutron scattering and transmission electron microscopy
      were carried out. The drug release and membrane transport experiments were
      performed by Franz type vertical diffusion cell and Sartorius Resorptionsmodell
      apparatus. According to our results liquid crystalline vehicles of lamellar and
      hexagonal structure formed by increasing the surfactant concentration. The drug
      release studies indicated, that the kinetic of the release strongly depend on the
      liquid crystalline structure, zero order release occurs from hexagonal structures
      and anomalous transport occurs from lamellar structures. The addition of
      chlorhexidine species to the systems modified the structure of the liquid
      crystalline system. As a results of liquid crystal-drug interaction the
      solubility of chlorhexidine base and its diffusion through lipophilic membranes
      increased in comparison with those of the chlorhexidine salts.

PMID- 11961907
TI  - ["Kroly Than" Pharmacy, Sopron, Hungary].
AB  - The hundred year-long history of the "Karoly Than" Pharmacy is surveyed. The
      widespread and versatile professional, humanitarian and public life activities
      from the turn of the century to the nationalisation and than to the privatisation
      are described. The paper also commemorates Professor Karoly Nikolics, the
      prominent director and scientist, who has outstanding merits in making the city
      of Sopron one of the major headquarters of Hungarian pharmacy.

PMID- 11961908
TI  - [Heroin. II. Preparation, hydrolysis, stability, pharmacokinetics].
AB  - Heroin is prepared by treating morphine with acetyl chloride or acetic anhydride.
      It is a simple reaction and the yields are generally quantitative. Nowadays the
      whole process is illegal. Morphine is the major alkaloid present in the opium
      poppy. Opium is manufactured illicitly then morphine is extracted from it in
      clandestine laboratories. Numerous studies were carried out on heroin to
      investigate its rate of hydrolysis. It has been shown that heroin is rapidly
      deacylated in aqueous solution at alkaline or acidic pH to form 6-acethylmorphine
      and finally, to morphine. Heroin also rapidly decomposes in biological medium
      yielding first 6-acetylmorphine and then morphine. Hydrolysis can be performed in
      blood and in tissue homogenates. Heroin can be administered by several routes.
      Smoking and intravenous administration are preferred, but intranasal,
      intramuscular and subcutaneous administration are also common. Recently, there
      has been a shift in heroin use patterns from injection to sniffing and smoking.
      Sharing of the injection equipment can result in several severe infectious
      diseases, such as AIDS, hepatitis B and C. Soon after administration, heroin
      metabolizes to 6-acetylmorphine and morphine. Most of the pharmacological
      activities of heroin are due to these active metabolites. Therefore, knowledge of
      distribution of 6-acetylmorphine and morphine is essential to understand
      pharmacological properties of heroin. Heroin, which is relatively nonpolar
      compound compared with morphine, has high lipid solubility facilitating rapid
      absorption from the bloodstream and passage through the blood-brain barrier. When
      heroin is administered by intravenously the drug takes 10 s to reach the brain
      i.e. pharmacological effects appear quickly.

PMID- 11961909
TI  - A 25-year follow-up of cognitive/behavioral therapy with 7,275 sexual offenders.
AB  - Outcome data are presented, grouped into 5-year cohorts, for 7,275 sexual
      offenders entering a cognitive/behavioral treatment program. Assessment variables
      included treatment completion, self-admission of covert and/or overt deviant
      behaviors, the presence of deviant sexual arousal, or being recharged for any
      sexual crime (regardless of plea or conviction). It proved possible to follow 62%
      for the cohort at 5 years after initiating treatment, but follow-up completion
      rates decreased with time. Outcomes were significantly different based on
      offender subtype, with child molesters and exhibitionists achieving better
      overall success than pedophiles or rapists. Prematurely terminating treatment was
      a strong indicator of committing a new sexual offense. Of interest was the
      general improvement of success rates over each successive 5-year period for many
      types of offenders. Unfortunately, failure rates remained comparatively high for
      rapists (20%) and homosexual pedophiles (16%), regardless of when they were
      treated over the 25-year period. Implications for clinical practice and future
      research are drawn.

PMID- 11961910
TI  - The effects of delayed rewards, tokens, and stimulant medication on sportsmanlike
      behavior with ADHD-diagnosed children.
AB  - Five children diagnosed with attention deficit/hyperactivity disorder
      participated in a summer program designed to evaluate behavioral and
      pharmacological treatments in a recreational setting. The effect of a contingency
      for increased sportsmanlike behavior, with and without the use of tokens, was
      examined during kickball games. The influence of stimulant medication was also
      examined for 3 of the children. A multiple-baseline, reversal design revealed
      that a delayed reward condition did not increase sportsmanlike behavior, whereas
      the addition of tokens (and praise) to the delayed reward increased sportsmanlike
      behavior for all 5 participants. Stimulant medication appeared to have very
      little influence on sportsmanlike behavior. Future directions for behavioral
      social skills interventions using a sports skills model are also discussed.

PMID- 11961911
TI  - Psychological impact of fire disaster on children and their parents.
AB  - Six weeks following a major wildfire, children's psychosocial functioning was
      examined. Employing a multimethod assessment approach, the short-term mental
      health consequences of the fire were evaluated. Individual adjustment was
      compared between families who reported high levels of loss as a result of the
      fire (high-loss group) and families who reported relatively low levels of loss
      resulting from the fire (low-loss group). Standardized assessment procedures were
      employed for children and adolescents as well as their parents. In general, high
      loss participants reported slightly higher levels of post-traumatic stress
      disorder (PTSD) symptoms and significantly higher scores on the Impact of Events
      Scale. PTSD symptoms reported by parents were generally significantly correlated
      with (but not concordant with) PTSD symptoms reported by their children. The high
      loss group scored significantly higher on the Resource Loss Index than did the
      low-loss group. Preexisting and comorbid disorders and previous stressors are
      described. A methodological framework for future studies in this area is
      discussed.

PMID- 11961912
TI  - Functional analysis of self-injurious behavior in an adult with Lesch-Nyhan
      syndrome.
AB  - A three-phase functional analysis was conducted to discover controlling variables
      of self-injury in a 28-year-old individual with Lesch-Nyhan syndrome.
      Experimental verification followed information-gathering and interpretive phases.
      Self-injurious responses were blocked to prevent harm to the participant;
      therefore, responses measured were precursors to self-injury. A multielement
      experimental design included four assessment conditions: social attention
      contingent on precursory behavior, attention contingent on behavior incompatible
      with precursory behavior, continuous attention and minimal attention. Highest
      rates of precursory behavior occurred during continuous attention and when
      incompatible behavior was reinforced. Social attention appeared to act as a
      discriminative stimulus for self-injurious behavior in this participant.

PMID- 11961913
TI  - Home-based cognitive-behavioral treatment of chronic, refractory obsessive
      compulsive disorder can be effective. Single case analysis of four patients.
AB  - Four patients with obsessive-compulsive disorder (OCD) were referred for home
      based cognitive-behavioral therapy. All patients had failed extensive trials of
      behavioral and cognitive therapy and pharmacotherapy in a variety of settings
      (e.g., outpatient, inpatient, and day program) and were generally considered
      chronic and refractory to treatment. Generalization from treatment sites to
      natural settings in which they lived did not occur. They were evaluated at
      baseline, after treatment, and at an 18-month follow-up using the Yale-Brown
      Obsessive Compulsive Scale. Conducting end-state functioning and reliable change
      assessment according to the methods specified by Jacobson and Truax, the authors
      found that 3 patients achieved clinically significant gains after treatment and 2
      patients maintained those gains at the 18-month follow-up. Data suggested better
      overall adjustment for 3 of the patients at follow-up. This study demonstrates
      the effectiveness of home-based cognitive-behavioral therapy for chronic,
      refractory OCD; implications for further, controlled trials are discussed.

PMID- 11961914
TI  - Stages of change. A critique.
AB  - The stages of change proposed by Prochaska and DiClemente have been applied to
      change efforts within and outside of formal treatment and in relation to
      virtually any problem behavior. This model has gained widespread popularity in
      health psychology and addictions and is being used to guide interventions and
      allocate treatment resources in several fields. In this article, the authors
      review 87 studies on the stages of change across problem behaviors. Research
      findings suggest that the proposed stages are not mutually exclusive and that
      there is scant evidence of sequential movement through discrete stages in studies
      of specific problem behaviors, such as smoking and substance abuse. Although the
      stage model may have considerable heuristic value, its practical utility is
      limited by concerns about the validity of stage assessments. The model's
      underlying concepts and alternative views of readiness for change are considered,
      along with directions for future research.

PMID- 11961915
TI  - The relations of anxiety sensitivity, experiential avoidance, and alexithymic
      coping to young adults' motivations for drinking.
AB  - The authors examined whether motivations for drinking alcohol are associated with
      the anxiety-related dispositional tendencies of anxiety sensitivity, experiential
      avoidance, and alexithymic coping. The authors administered the Anxiety
      Sensitivity Index, Experiential Avoidance Scale, 20-item Toronto Alexithymia
      Scale, Revised Drinking Motives Questionnaire, and a demographics questionnaire
      to 182 university drinkers. In multiple regressions, the dispositional factors
      significantly predicted the risky drinking motives of coping, enhancement, and
      conformity. Coping and enhancement motives were significantly predicted by
      experiential avoidance. Conformity motives were significantly and independently
      predicted by anxiety sensitivity and alexithymia. The process of experiential
      avoidance mediated the bivariate correlation between anxiety sensitivity and
      coping-motivated drinking to a greater extent than did the process of alexithymic
      coping. The authors discuss the observed relations in regard to the psychological
      functions of drinking behavior that may portend the development of heavy drinking
      and alcohol problems in dispositionally vulnerable individuals. They also review
      implications for refinements of behavior therapy for problem drinkers.

PMID- 11961916
TI  - Use of the timeout ribbon procedure during community-based instruction.
AB  - Involvement in community-based instruction can be adversely affected when
      students engage in behavior that interferes with participation in instruction. A
      multiple probe across settings design with an embedded reversal was used to
      investigate the effectiveness of the nonseclusionary timeout ribbon procedure for
      two middle-school students with moderate mental retardation in community and
      school settings. An athletic wristband served as the timeout ribbon, which
      functioned as the stimulus for the availability of reinforcement. When the
      student was wearing the wristband, he could earn reinforcers. On occurrence of
      inappropriate behavior, the wristband was removed and the student was placed in
      nonseclusionary timeout. Implementation of the timeout ribbon procedure resulted
      in target behaviors reduced to zero occurrences for both youths. This was
      maintained at a 2-week follow-up, even as the reinforcement schedule was thinned.
      The timeout ribbon procedure provided an efficient, effective, and socially valid
      means of supporting positive behavior across settings for these students.

PMID- 11961917
TI  - Regulatory reform is a health care issue.

PMID- 11961918
TI  - Consumer-directed health care. The goals: more choice, more control.

PMID- 11961919
TI  - Reach out and teach someone.

PMID- 11961920
TI  - PPOs evolve, build on strengths of managed care.

PMID- 11961921
TI  - Rising health care costs: what lessons for managed care? An interview with Stuart
      Altman.

PMID- 11961922
TI  - A contingency plan for unpredictable circumstances. Terrorist attacks prompt
      investment in enhanced systems.

PMID- 11961923
TI  - Approaches to asthma care. Medicaid health plans pilot programs to combat a
      complex health issue.

PMID- 11961924
TI  - Managing common geriatric conditions.

PMID- 11961925
TI  - At your service. Programs raise customer satisfaction levels while lowering
      costs.

PMID- 11961926
TI  - Blueprint for a successful quality improvement project.

PMID- 11961927
TI  - Building a better Website. Incentives for members to visit often.

PMID- 11961928
TI  - By the numbers. Most Medicaid managed care plans target asthma.

PMID- 11961929
TI  - Modernization of professional system continues. OIIQ files brief on nursing
      practice in mental health and psychiatry.

PMID- 11961930
TI  - The OIIQ releases its study on the quality of nursing care.

PMID- 11961931
TI  - Smart card: order expresses reservations.

PMID- 11961932
TI  - Clinical research is part of what we do: the experience of one medical intensive
      care unit.
AB  - Clinical research remains a desired goal of the profession. Unfortunately, the
      methods we have traditionally used to spark the interest and commitment of
      clinicians have not been universally accepted or successful in attaining our
      goal. Although nothing is inherently wrong with journal club meetings, research
      forums, and partnering with academicians, these methods of inspiring research
      rarely do so. Partially, that failure is because a leader, perhaps a cheerleader,
      is needed, someone who is willing to teach, support, coach, and call to task the
      clinicians who wish to "do" clinical research. As noted by Hanneman, the presence
      of a unit-based expert is necessary for the "catalytic conversion" of others:
      "Expert nurses methodically build non-expert nurse expertise through flexible,
      context dependent strategies." The mentor must understand the abilities, the
      background, and the time commitments of the clinicians so that the support is
      appropriate for the task. For example, an academician friend who wished to do
      some research "partnering" with some clinicians in a practice area of interest
      thought that the main role of the clinicians would be as data collectors. In this
      collision of philosophies and understanding, the clinicians, who wanted the
      academician to "show them" how to do the research and teach them at each step,
      were angered by the academician's perspective of their potential to contribute to
      the research process. The project was not successful because neither the
      clinicians nor the academician understood the perspective or expectations of the
      other. For clinical research to thrive and prosper, indeed to become part of what
      we do in practice, we must learn from the clinicians who can tell us what works
      and what does not. The comments of the clinicians recorded in Table 1 are filled
      with advice, should we choose to listen. Clinical research is part of what our
      MICU does. The clinicians are proud of their accomplishments, and some are now
      mentoring others in the process. The success of the program can easily be
      duplicated in other settings. I hope that we begin to acknowledge the power of
      teaching research as part of clinical practice and start to reward and
      acknowledge our clinicians for their involvement.

PMID- 11961933
TI  - Using ambulatory electrocardiography during recovery from cardiac surgery.

PMID- 11961934
TI  - Noninvasive blood pressure monitoring.

PMID- 11961935
TI  - Am I legally responsible for the nursing care or advice that I provide for my
      neighbors and friends?

PMID- 11961937
TI  - When obtaining a wedge pressure, how will I know that the balloon is deflated?

PMID- 11961938
TI  - Survival kit for nurse managers.

PMID- 11961936
TI  - How deeply should I go when I suction an endotracheal (ETT) or tracheostomy tube
      (TT)?

PMID- 11961939
TI  - Recognizing and rewarding preceptors: do you bother? A survey.

PMID- 11961940
TI  - Use of charcoal hemoperfusion.

PMID- 11961941
TI  - The importance of using the right words.

PMID- 11961942
TI  - Herbal remedies: drug-herb interactions.
AB  - Controlled clinical studies are needed to clarify and determine the clinical
      importance of drug-herb interactions. However, it is unlikely that this
      information will be forthcoming except as anecdotal reports. Patients taking
      drugs with a narrow therapeutic index (cyclosporine, digoxin, hypoglycemic
      agents, lithium, phenytoin, procainamide, theophylline, tricyclic
      antidepressants, and warfarin) should be discouraged from using herbal products.
      All drugs with a narrow therapeutic index may either have increased adverse
      effects or be less effective when used in conjunction with herbal products. More
      research is required to define the interactions. When adverse reactions are
      experienced with drug therapy, patients must always be queried as to their intake
      of herbal products: what they are taking in pills and tincture form, what they
      are drinking as teas, and what they are eating from their garden.

PMID- 11961943
TI  - Using carvedilol to treat heart failure.

PMID- 11961944
TI  - Monitoring arterial blood pressure: what you may not know.
AB  - Hemodynamic monitoring is a costly procedure, both materially and with regard to
      nursing time involved to ensure proper functioning of the monitoring system and
      correct interpretation of the data obtained. Dynamic response testing is the
      ideal method of confirming the ability of a monitoring system to accurately
      reproduce hemodynamic waveforms. MAP is a stable hemodynamic parameter, because
      it is least affected by monitoring method, catheter insertion site, the dynamic
      response characteristics of the catheter system, and wave reflection. MAP
      provides the best estimate of central aortic pressure and is the main hemodynamic
      parameter monitored by the neurohormonal system to control blood pressure. The
      superior informational value of MAP provides strong support for its preferred use
      in clinical practice, especially when use of vasoactive drugs is started or the
      dosages of these drugs are titrated. However, numerically satisfactory ABP or MAP
      values are not necessarily related to adequate peripheral tissue perfusion and
      organ system function. For optimal management of patients, data obtained from
      assessment tools such as hemodynamic monitoring devices must be integrated with
      information gained from clinical assessment of patients' status.

PMID- 11961945
TI  - Caring for adolescents in the adult intensive care unit.

PMID- 11961946
TI  - [Denise Paul: "I have always loved school!" (interview by Odile Lamy)].

PMID- 11961947
TI  - [Recognition of the complexities of geriatric nursing].

PMID- 11961948
TI  - [Clinical and ethical considerations. Attendance of the person with loss of
      autonomy and his family].

PMID- 11961949
TI  - [The problems for the aged living at home].

PMID- 11961950
TI  - [Psychotropic drugs and the aged].

PMID- 11961951
TI  - [Abnormal scarring and skin complications].

PMID- 11961952
TI  - [The grief of nurses].

PMID- 11961953
TI  - Urgent: "operation recruit".

PMID- 11961954
TI  - [Pedro Lain Entralgo, physician and humanist].
AB  - This speech of the president of the Chilean Academy of Medicine, Dr Alejandro
      Goic, is a tribute to the memory of the Spanish physician, scholar, historian,
      writer and intellectual Dr. Pedro Lain Entralgo, who died in Madrid on June 4,
      2001, at the age of 93. On that occasion, the Spanish newspaper "El Pais" defined
      him as the last humanist. The Spanish civil war started when Lain was 28 years
      old and he aligned with Franco's supporters. In 1940, when he founded the
      magazine "El Escorial", he was separated from the official party. He and other
      intellectuals declared themselves in an "interior exile". His autobiographical
      book, "Lightening the burden on the conscience" refers to his painful personal
      history. He obtained the History of Medicine chair, at the Complutense
      University, at the age of 34 and remained at that post until his retirement in
      1978. His intellectual production is magnificent and calls to a mutual
      understanding, hope, friendship and love. Outstanding, among others, are his
      books "The wait and hope", "Theory and reality of the other", "Spain as a
      problem", "Medicine and history", "The clinical history", "Patient physician
      relationship", "Medical anthropology". He directed the collective work composed
      of seven volumes, called "Universal History of Medicine". He was a member of the
      Royal Academies for Language, History and Medicine. In Chile, he was named
      honorary member of the Faculty of Medicine of the University of Chile and of the
      Academies of Language, History and Medicine. He dictated a course of Medical
      Anthropology that had a profound impact on the thought of Chilean physicians. In
      1949 he wrote that Chile was the most solid state of Latin America and that
      "Chile needs to leave his traditional calm, through a historical gesture, and
      create the river beds required by his magnificent spiritual and geographical
      gifts. There is a lack of a beautiful craziness". It was an invocation for an
      understanding with our neighboring countries "for ever and ever".

PMID- 11961955
TI  - [Infant mortality and socioeconomic indicators in Chile: 1985-1999].
AB  - BACKGROUND: The link between economy and some public health indicators like
      Infant Mortality Rate (IMR) is widely demonstrated. AIM: To explore the
      relationship between some economic indicators and infant mortality in Chile
      between 1985 and 1999. MATERIAL AND METHODS: An ecological study, obtaining
      information from Demographic Annual Reports edited by the National Institute of
      Statistics, Health Ministry, Planning Ministry and the Central Bank. RESULTS:
      There is an inverse association between the Gross National Product, per capita
      and Real Salary Index and a direct relationship between inflation and
      unemployment rates with an increased infant mortality. CONCLUSIONS: The reduction
      in infant mortality observed in Chile depends more on socio demographic than on
      economical factors.

PMID- 11961956
TI  - [The myth of autonomy].

PMID- 11961957
TI  - [Ultraviolet radiation producing erythema in Valdivia. A comparison among
      satellite data, a radiative transfer model and ground-based observations].
AB  - To evaluate dose rates and daily doses (DDE) at Valdivia in Southern Chile,
      ultraviolet irradiances recorded every 15 min from 1998 to 2000 with a high
      resolution spectroradiometer were weighted with an erythemal action spectrum.
      Exposure times to get one MED (210 J/m2) in Summer are 10, 12, 18 and 24 min for
      skin types I trough IV respectively. DDE estimations included in NASA Web
      products overestimate measurements by 16% on average in Summer, with an absolute
      uncertainty of 980 J/m2 at the 95% level. Observed dose rates for clear days are
      in fair agreement with the numerical output from a numerical model, suggesting
      that acute episodes can be predicted if total ozone can be forecasted and the
      population is instructed on corrections for cloud effects.

PMID- 11961958
TI  - [Resistance to Streptococcus pneumoniae to penicillin and its association with
      clinical and epidemiological factors].
AB  - BACKGROUND: Penicillin and third generation cephalosporin resistant pneumococcal
      isolates have emerged in Chile, mainly in the pediatric population. These
      isolates complicate therapeutic alternatives, specially among patients with
      central nervous system infections. AIM: To assess the frequency of penicillin and
      third generation cephalosporin resistance among isolates obtained from pediatric
      patients with invasive pneumococcal infections, and to study serotypes and
      clinical risk factors associated with resistance. MATERIAL AND METHODS:
      Microbiological isolates obtained from children between April 1994 and May 1999
      with pneumococcal invasive infections, were serotyped and analyzed according to
      their susceptibility to penicillin and cefotaxime by E-test and broth
      microdilution testing. Potential risk factors studied included patient's age,
      previous antibiotic use or admissions, comorbidity, and serotypes. RESULTS:
      Seventy eight patients were studied. Penicillin-resistant pneumococcal isolates
      were detected in 35.9% of cases (21.8% with intermediate and 14.1% with high
      level resistance) without significant variation among different clinical
      conditions. Most of the high level penicillin-resistant pneumoccocal isolates had
      MIC > or = 4 micrograms/mL (8 out of 11 strains). One third of penicillin
      resistant isolates also expressed cefotaxime resistance. Multivariate analysis
      indicated an age < or = 36 months (OR = 6.8; IC 95%: 1.4 to 33.5) and serotype 14
      (OR = 6.3; IC 95%: 1.7 to 23.3) as factors associated with penicillin resistance.
      CONCLUSIONS: One third of the invasive pneumococcal isolates obtained from
      pediatric patients were resistant to penicillin. Risk factors involved a younger
      age and pneumococcal isolates belonging to serotype 14.

PMID- 11961959
TI  - [Association between cleft lip/palate phenotype and non syndrome microsatellite
      markers located in 6p, 17q and 19q].
AB  - BACKGROUND: In the search of the major genes responsible for the genetic etiology
      of Nonsyndromic Cleft Lip and Palate (NSCLP), an association study between this
      malformation and four molecular markers, F13A1 and EDN1 (6p), D17S579 (17q) and
      BCL3 (19q), was done. AIM: To determine, in a Chilean population, the presence of
      NSCLP susceptibility regions, as proposed for Caucasian populations in the 6p,
      17q and 19q chromosomal regions. MATERIAL AND METHODS: A sample of unrelated
      NSCLP patients, that belonged to Simplex (Sx) and Multiplex (Mx) families, was
      analyzed. Blood donors were used as a control group (Co). The DNA of the four
      markers was amplified by means of PCR, their products analyzed by PAGE
      denaturants and visualized by silver staining. Statistical analysis was performed
      using chi 2 log ratio. RESULTS: Allele frequency distribution of D17S579 was
      significantly different in all patients with NSCLP and their subgroups, when
      compared to control subjects. Significant differences in EDN1 frequency were
      observed between the total groups of NSCLP patients and those pertaining to the
      Mx subgroup, when compared to controls. Differences in F13A1 distribution were
      only observed between NSCLP-Mx patients and controls. There was a slight
      difference in BCL3 distribution, between the total sample of NSCLP patients and
      controls. CONCLUSIONS: Our results support the hypothesis of the existence of
      cleft susceptibility regions in 6p and 17q. The small significance of BCL3,
      suggests that ethnicity can influence the interactions between involved genes.

PMID- 11961960
TI  - [Classic and molecular methodologies for the identification of Enterococcus
      species].
AB  - BACKGROUND: Enterococcus is a bacterial genus with low virulence. However, in the
      last years, the importance of some enterococcus species as nosocomial pathogens
      has increased, specially due to their resistance to some antimicrobial. AIM: To
      identify enterococcus strains using classical biochemical techniques and genomic
      amplification with Polymerase Chain Reaction (PCR). MATERIAL AND METHODS: Three
      hundred and five enterococcus strains, isolated between 1996 and 1999, from
      different clinical specimens in hospitals and other centers of the VIIIth Region
      of Chile, were studied. The isolates were identified, to the species level,
      according to the scheme proposed by Carvalho et al. Identification of some
      strains was confirmed by PCR. RESULTS: Eighty nine percent of isolates were
      identified as E foecalis, 10.2% as E foecium and 3.3% as other species.
      CONCLUSIONS: PCR is a fast and promising technique, useful in the identification
      of Enterococcus species.

PMID- 11961961
TI  - [Resting energy expenditure in obese and non-obese Chilean subjects: comparison
      with predictive equations for the Chilean population].
AB  - BACKGROUND: The commonly used predictive equations to calculate resting energy
      expenditure (REE) can yield inaccurate results. AIM: To compare measured REE,
      with estimated REE in normal and obese adults. To develop specific predictive
      equations for our population. PATIENTS AND METHODS: Eight hundred sixteen women
      aged 18 to 74 years old with a body mass index (BMI) between 18.5 and 69.7 kg/m2
      and 441 men aged 18 to 71 years old with a BMI between 185 and 67.9 kg/m2 were
      studied. REE was measured by indirect calorimetry and fat free mass by tetrapolar
      bioimpedance. REE was also estimated using FAO/WHO (F/W) and Harris-Benedict
      (H/B) equations. RESULTS: Measured REE in controls was 20.7 +/- 1.9 and 23.6 +/-
      3.3 kcal/kg/day in women and men respectively. The figures for overweight women
      and men were 19.8 +/- 1.9 and 20.0 +/- 2 kcal/kg/day, for obese women and men
      were 18.3 +/- 1.7 and 19.0 +/- 1.8 kcal/kg/day and for morbidly obese women and
      men, were 16.9 +/- 1.8 and 16.1 +/- 1.7 kcal/kg/day. When REE was corrected for
      fat free mass, no differences between controls and different degrees of obesity,
      were observed. The difference between estimated and measured REE ranged from -420
      to 617 kcal in women and from -400 to 900 kcal in men. The equations derived
      using data obtained in the present study, showed a better predictive accuracy.
      CONCLUSIONS: An important error was detected when REE was predicted using FAO/WHO
      or Harris Benedict equations, in Chilean obese subjects. Therefore these
      equations must be used with caution, local equations must be devised or resting
      energy expenditure must be measured by indirect calorimetry.

PMID- 11961962
TI  - [An Elisa stool test to detect Helicobacter pylori infection].
AB  - BACKGROUND: Infection with Helicobacter pylori is frequent in Chile, and a good
      test for its diagnosis ideally should be non-invasive, fast, easy and
      inexpensive. AIM: To report the use of an immunoassay test, that detects antigens
      of Helicobacter pylori in stools. MATERIAL AND METHODS: One hundred and four
      patients that required an upper gastrointestinal endoscopy were studied. Stool
      samples were analyzed using an enzymatic immunoassay. These results were compared
      with those obtained with the urease test and microscopic examination of smears
      taken from biopsies obtained during the diagnostic endoscopy. RESULTS: In 81 of
      83 patients considered to have the infection according to the endoscopic tests,
      the antigen was also present in the stools. The test was negative in 16 of 21
      patients considered to be without the infection. The resulting sensitivity and
      specificity for the immunoassay was thus 97.6 and 76.2% respectively, with
      positive and negative predictive values of 92.4 and 88.9%, respectively.
      CONCLUSIONS: These results are in agreement with those reported in the
      literature. Further studies are needed to define its usefulness in massive
      screening, follow up after antibiotic treatments or the detection of coccoid
      forms of Helicobacter pylori.

PMID- 11961963
TI  - [Length of lactational amenorrhea in an urban population of Temuco, Chile].
AB  - BACKGROUND: Studies done in Santiago, Chile show that menses return before the
      sixth month of puerperium in 50% of lactating women, even in those that continue
      with exclusive breast feeding. AIM: To study the length of lactational amenorrhea
      in a group of women living in Southern Chile. MATERIAL AND METHODS: One hundred
      fourteen women giving exclusive breast feeding, were followed from the third
      postpartum month, to determine the length of lactational amenorrhea. Its
      relationship with general characteristics of the mothers and children and breast
      feeding pattern was also studied. RESULTS: Sixty six women (58%) recovered their
      menses before the 6th postpartum month and their length of lactational amenorrhea
      was 101 +/- 5 days. In the rest of the sample, the length was 277 +/- 10 days. No
      differences in characteristics of the mothers and children or breast feeding
      pattern, were observed between these two groups. CONCLUSIONS: A short lactational
      amenorrhea is common in the Chilean population. Clinical characteristics or
      pattern of breast feeding do not explain the length of LA in this population.

PMID- 11961964
TI  - [Reflections at the start of a new year].
AB  - The arrival of a new year stimulated the Editor to reflect on what has been
      recently accomplished in the Revista and on what is planned for its immediate
      future. In 2001 the electronic version at the website www.scielo.cl started to
      reproduce the full contents of most articles. Members of the International
      Advisory Committee submitted reviews and special articles by invitation. The
      input of manuscripts increased and most of them have been improved through the
      peer review process. A Symposium held in August stimulated the editors of a vast
      proportion of Chilean clinical and biomedical journals to interchange
      experiences. The 5 years tenure of the Editor in Chief was extended for a second
      period. For the year 2002, improvements will be made in the editorial process
      while the Revista commemorates 130 years of continuous publication, being among
      the 20 oldest medical journals in the world.

PMID- 11961965
TI  - [Prediction of the length of stay in Intensive Care Units using artificial neural
      networks].
AB  - BACKGROUND: The prediction of the length of stay at the moment of hospital
      admission is of utmost importance. Many studies have used lineal models to
      predict this variable, but there are inherent limitations to these models. The
      use of non lineal models has been scarce. AIM: To develop a non lineal model to
      predict length of stay in intensive care units. MATERIAL AND METHODS:
      Retrospective analysis of 294 patients admitted to two intensive care units in
      Santiago, Chile. The severity of the disease motivating the admission was
      nominally quantified. This and other physiological variables were included in the
      model. The length of stay was modeled using Artificial Neural Networks. RESULTS:
      The model yielded an error of 8.7% (3.6 +/- 0.4 days, CI 95%) and a correlation
      coefficient of 0.9 (p < 0.001) for the prediction of length of stay. Using net
      sensitivity analysis, the model determined that gastrointestinal diseases,
      infections and respiratory problems were the main causes of prolongation of
      intensive care unit stay. CONCLUSIONS: Intensive care units should have, in the
      future, computer systems that gather vital information to predict length of stay.

PMID- 11961966
TI  - [Status of hereditary hypercoagulability and cerebral venous thrombosis. Report
      of 3 cases].
AB  - Hereditary hypercoagulability has been identified as risk factor in approximately
      30% of cerebral venous thrombosis cases. We report three females with this
      association. A 38 years old female with a history of deep venous thrombosis of
      the lower limb, presented with headache, vomiting and a generalized seizure.
      Magnetic resonance angiography showed a partial thrombosis of the left lateral
      and superior longitudinal venous sinuses. Coagulation study showed a resistance
      to activated C protein and factor V Leyden. A 42 years old woman with a history
      of deep venous thrombosis, presented a right hemiplegia during a hospitalization.
      Magnetic resonance showed a left lateral hemorrhagic infarction. Magnetic
      resonance angiography showed an absence of signal in three venous sinuses.
      Coagulation study showed a protein C deficiency. A 17 years old woman presented a
      right hemiparesis in the sixth day of puerperium. CAT scan showed a left
      frontoparietal subcortical venous infarction. Coagulation study showed an
      antithrombin III deficiency.

PMID- 11961967
TI  - [Occlusion of the macular branch of the central retinal artery].
AB  - We report a 54 years old female on oral anticoagulant treatment with a mitral
      valve disease, with a history of two transient ischemic attacks and a decreased
      visual acuity. She was assessed by an ophthalmologist and signs of retinal
      vascular disease were found. During follow up, the patient experienced an acute
      unilateral loss of vision in the left eye. Fundoscopy revealed an obstruction of
      a macular branch of central retinal artery. Aspirin was added to oral
      anticoagulants and one month later, the patient experienced an upper
      gastrointestinal bleeding. After four months of follow up, there is no recovery
      of left eye vision.

PMID- 11961968
TI  - [Surgery for mitral valve insufficiency].
AB  - BACKGROUND: Ischemic mitral regurgitation (IMR) is a severe condition which may
      be best treated by surgery, notwithstanding a relatively high mortality rate.
      OBJECTIVES: To evaluate the results of mitral valve replacement or repair in
      patients with IMR. PATIENTS AND METHODS: Retrospective review of the clinical
      records in 29 patients with IMR who were surgically treated from 1990 to 1999.
      They represent 8% of surgical procedures on the mitral valve. RESULTS: Mean age
      was 67 +/- 9 years. Surgery was performed urgently in 19 patients (66.5%). NYHA
      functional class was 3.4 +/- 0.8. The mechanism of IMR was annular dilatation and
      spreading of papillary muscles in 18 patients, papillary muscle rupture in 9 and
      fibrosis in 2. Mitral valve replacement was performed in 14 patients and mitral
      valve repair in 15. Twenty four patients (83%) had concomitant myocardial
      revascularization. Overall surgical mortality was 24%; 26% for mitral replacement
      and 13% for mitral valve repair (p = 0.215). On follow up of 26 +/- 33 months,
      one year survival was 76 +/- 0.8% and 5 years survival was 59 +/- 12%. Excluding
      in hospital mortality, survival was 100% at one year and 78 +/- 14% at 5 years.
      Functional class improved in all survivors, to 1.4 +/- 0.5. Late
      echocardiographic evaluation of patients with mitral valve repair showed absence
      of mitral regurgitation in 58%, 1+ MR in 17% and 2+ MR in 25%. CONCLUSION: In
      spite of a high perioperative mortality, surgery for IMR is a valuable procedure
      for patients with an otherwise highly lethal disease.

PMID- 11961969
TI  - [Incidental finding of inguinal hernia sac cancer].
AB  - The presence of cancer in a hernia sac is uncommon. The tumor can involve the
      hernia sac, the herniated mass or be external to the hernia sac. We report two
      cases with this condition. A 68 years old male was operated of a right inguinal
      hernia. During surgery, several white nodules were noted in the internal side of
      hernia sac. The same lesions were present in the mesentery. Pathological study
      revealed an adenocarcinoma. The primary tumor was not located and the patient
      died one and a half years after the procedure. A 62 years old male was operated
      due to an irreducible inguinal mass, seven months after a subtotal gastrectomy
      for gastric cancer. During the resection of the mass, metastasis implants in the
      mesenteric adipose tissue were noted. A mini laparotomy was performed and an
      extensive peritoneal tumor dissemination was found. The patient died two months
      after surgery.

PMID- 11961970
TI  - [Practice of Internal Medicine in Latin America. Role of the internist].
AB  - This article explores the causes of the crisis in the role of internists. As in
      the United States, the progressive specialization of internists lead to a
      dehumanized, expensive and technical practice of medicine. Aiming to better
      incomes and prestige, more than 60% of internists practice as specialists.
      Primary care physicians, with a very low rate of problem solving, cover 75% of
      consultations. Specialists, with increasing costs, cover the rest of
      consultations. Patients, medical schools and health organizations are claiming
      the return of the general internal medicine specialist. To increase the interest
      for general internal medicine, several strategies are applicable. Medical
      students interested in general internal medicine could receive a focused
      training, provided by these specialists. A greater emphasis should be put on
      primary care. More independent, secondary care diagnostic and treatment centers,
      should be created. Continuous medical education should be done with periodical re
      certification of physicians. The public health system should increase its wages
      and the generalist view should be maintained by physicians when practicing at
      their private offices.

PMID- 11961971
TI  - [Being a geriatrician].

PMID- 11961972
TI  - [Drug industry dependence].

PMID- 11961973
TI  - [Physical activity among pregnant women in relation to pregnancy-related
      complaints and symptoms of depression].
AB  - BACKGROUND: The possible association between physical activity and symptoms of
      depression during pregnancy and post partum has not been examined in Norway. The
      objectives of this study were to track levels of physical activity of pregnant
      women and to examine possible differences in symptoms of depression and prenatal
      complaints. MATERIALS AND METHODS: 203 pregnant women in Oslo aged 18 to 40
      completed the depression scale of the Hospital Anxiety and Depression Scale (HADS
      D) and a self-developed questionnaire. RESULTS: Their average physical activity
      was two hours and 36 minutes per week; 70% were active during at least two
      trimesters. The most popular activities reported were walking, aerobics and
      swimming. Respondents who had high score on the HADS-D test during pregnancy
      and/or post partum had significantly more pre-natal complaints than those with a
      normal score. Pregnant women defined as moderately physically active during the
      third trimester had significantly lower scores on the HADS-D test six weeks after
      birth than the not-active. There was also a significant inverse correlation
      between test score and amount of physical activity. INTERPRETATION: This study
      indicates that women who are physically active during pregnancy have lower scores
      on a test measuring depressive symptoms during pregnancy and post partum.
      However, randomised controlled prospective studies are necessary in order to
      confirm the possible association.

PMID- 11961974
TI  - [A critical evaluation of side effect data on COX-2 inhibitors].
AB  - BACKGROUND: Celecoxib and rofecoxib have been used in Norway since 2000. These
      cyclooxygenase 2 inhibitors (COX-2 inhibitors) have no better clinical efficacy
      than older non-steroid anti-inflammatory drugs (NSAIDs) in the treatment of
      rheumatoid arthritis or osteoarthritis, but may possibly lead to a lower
      incidence of upper gastrointestinal ulcers. MATERIAL AND METHODS: Published and
      unpublished clinical data on side effects were examined and interpreted. The aim
      was to evaluate the general safety of these new drugs compared with older NSAIDs.
      RESULTS: The incidence of side effects is addressed in two large published
      studies comparing COX-2 inhibitors with other NSAIDs. Only rofecoxib showed an
      unequivocal lower incidence of complicated upper gastrointestinal ulcers.
      However, the incidence of serious side effects was significantly higher in the
      rofecoxib group. In the other study there was a trend towards more serious side
      effects in the celecoxib group. INTERPRETATION: The available clinical data do
      not suggest that COX-2 inhibitors are safer drugs than other NSAIDs.

PMID- 11961975
TI  - [Reduced use of restricted-prescription preparations in general practice].
AB  - BACKGROUND: General practitioners in our community found that the use of drugs
      with restrictions on prescription was twice that of a neighbouring community, and
      made an effort at cutting down on the prescription of such drugs. MATERIAL AND
      METHODS: A retrospective analysis of this reduction is presented. RESULTS: The
      reduction observed was 33% over one year. The number of prescriptions in the
      neighbouring community remained unchanged. INTERPRETATION: The comparison with
      the neighbouring community was a good starting point for change. The most
      important contributing factor was probably the consistent approach of the doctors
      involved.

PMID- 11961976
TI  - [Churg-Strauss syndrome after treatment with Singulair (montelukast)].
AB  - BACKGROUND: Montelukast is the only available antileukotriene drug in Norway. It
      works against the inflammation, bronchospasm and airway oedema caused by
      leukotrienes. In the literature there are some reports on an association between
      the use of the leukotriene antagonists zafirlukast, pranlukast, montelukast and
      the appearance of Churg-Strauss syndrome. This rare syndrome is a systemic
      vasculitis characterized by allergic rhinitis, asthma and prominent peripheral
      blood eosinophilia. MATERIAL AND METHODS: This is a case report of the appearance
      of Churg-Strauss syndrome in a 20-year-old asthmatic woman treated with
      montelukast and with no recent oral corticosteroid use. INTERPRETATION: To our
      knowledge, this is the first report in a Nordic country of an association between
      montelukast and Churg-Strauss syndrome. Although this is a rare association, the
      clinicians need to be vigilant in all patients who develop systemic symptoms when
      starting treatment with leukotriene antagonists.

PMID- 11961977
TI  - [The somatostatin receptor family--a window against new diagnosis and therapy of
      cancer].
AB  - BACKGROUND: The peptide hormone somatostatin (SST) inhibits secretion from a wide
      variety of both endocrine and exocrine cells. It functions as a neurotransmitter
      and plays an important role in regulation of cell proliferation and
      differentiation. SST exerts its effects through binding to specific surface
      membrane receptors. MATERIAL AND METHODS: The article presents a literature-based
      review of the somatostatin receptor (SSTR) family, and diagnostic and therapeutic
      strategies based upon SSTR expression in neuroendocrine (NE)
      gastroenteropancreatic (GEP) tumours. RESULTS: Five different human SSTR subtypes
      have been characterised (SSTR1-5), and their genes cloned. The receptors are G
      protein coupled, and binding activates several different signal mechanisms. SSTRs
      have a characteristic expression pattern both in the central nervous system and
      in peripheral organs. Many tumour cell lines as well as the majority of human
      tumours express SSTR mRNAs, usually more than one subtype. The frequency of
      expression is especially high in NE GEP tumours. SSTR scintigraphy has become an
      important diagnostic tool for staging of NE GEP tumours and it may also predict
      sensitivity to treatment with somatostatin analogues. These are regarded as the
      main choice for symptomatic treatment of hormone related syndromes related to NE
      GEP tumours. In contrast, the antitumour effects of somatostatin analogues in
      patients have been rather disappointing. More encouragingly, radiotherapy with
      radiolabeled somatostatin analogues has more recently been carried out with
      survival benefit. Gene therapy has shown promising results in animal studies.
      INTERPRETATION: Increased molecular understanding of the SSTR family and
      especially how the receptors are being regulated will probably lead to the
      development of new diagnostic and therapeutic strategies against cancer.

PMID- 11961979
TI  - [Hypokalemia can accelerate the development of cerebrovascular and cardiovascular
      disease].
AB  - BACKGROUND: Hypokalaemia is known to precipitate cardiac arrhythmias.
      Hypokalaemia can also give rise to adverse cardiovascular effects not related to
      arrhythmias. MATERIAL AND METHODS: This article presents an evaluation of the
      relevant literature describing adverse effects of hypokalaemia and beneficial
      effects of potassium supplementation on cerebrovascular and cardiovascular
      disease. RESULTS AND INTERPRETATION: Diuretics-induced hypokalaemia may offset
      the beneficial effects of blood pressure reduction on cardiovascular events. In
      several epidemiological studies high intake of potassium in the food was
      associated with reduced risk of developing a stroke. Fruit and vegetables contain
      potassium, and an inverse correlation between intake of these nutrients and
      stroke has been described. In spontaneously hypertensive rats, potassium
      supplementation in the diet markedly reduced the risk of death, brain haemorrhage
      and infarct. Potassium reduces oxidative stress and proliferation of smooth
      muscle cells, i.e. factors involved in the development of atherosclerosis, and
      may have an antithrombotic effect.

PMID- 11961978
TI  - [Hyperprolactinemia and prolactinemia--investigation and treatment].
AB  - BACKGROUND: Prolactinoma represents the most commonly occurring hormone-secreting
      pituitary adenoma. The majority of prolactinomas are small, only rarely do we
      find larger prolactinomas, so-called macroadenomas. They are almost exclusively
      benign. The symptoms are mainly caused by elevated prolactin levels and result in
      changes to the reproductive and sexual function. In cases of macroprolactinomas,
      symptoms caused by local mass effects can be seen. A variety of other conditions
      may also cause hyperprolactinaemia; the goal of the examination is to identify
      the cause. MATERIAL AND METHODS: We have reviewed recent literature and compared
      findings with current management of hyperprolactinaemia and prolactinoma in
      Norwegian university hospitals. RESULTS AND INTERPRETATION: The primary treatment
      is medical, intended to normalize prolactin levels, restore gonadal function, and
      reduce tumour size. With the new selective dopamine agonists, the treatment is
      often simple and efficient, but not all patients are in need of treatment.

PMID- 11961980
TI  - [High-risk pregnancy, costs and DRG reimbursement].
AB  - BACKGROUND: The aim of this study was to measure actual costs of delivery of
      women with high-risk pregnancies in Norway. We calculated the cost difference
      between Caesarean section delivery and vaginal delivery and compared costs and
      the reimbursement received by hospitals. The present Norwegian financial system
      for hospitals has two components: a government reimbursement based on diagnosis
      related groups (DRG) covering, in principle, half of hospital costs, and a basic
      budget received as a block grant. MATERIAL AND METHOD: The study included 75 high
      risk pregnant women. We used a prospective, individual bottom-up method based on:
      1) hospital stay and the resources required, 2) operating theatre costs, 3) other
      major procedures, and 4) material and medication costs. Overhead costs (basic and
      general costs) were added on the basis on five key variables: 1) number of
      admittances (length of stay), 2) number of discharges, 3) number of employees, 4)
      floor space, and 5) number of PCs. The total cost for each patient was compared
      with the reimbursement received. RESULTS: We found that the reimbursement did not
      cover actual costs. Calculations were made for Caesarean and vaginal deliveries
      respectively: Mean cost of a Caesarean delivery was NOK 96,556, compared to a DRG
      reimbursement of NOK 47,137; mean cost of a vaginal delivery was NOK 62,136, with
      a DRG reimbursement of NOK 27,146.

PMID- 11961981
TI  - [A man with deep venous thrombosis, transient ischemic attacks and increasing
      sedimentation rate].

PMID- 11961982
TI  - [Interactions between drugs and alcohol].

PMID- 11961983
TI  - [Diagnosis and treatment of dementia].
AB  - BACKGROUND: Dementia is one of the most common conditions in the elderly. In
      Norway the total prevalence is about 60,000. MATERIAL AND METHODS: The paper is
      based on the author's clinical experience and a review of the literature.
      RESULTS: No biological marker exists for Alzheimer's disease and other dementias.
      The diagnostic work-up thus consists of a comprehensive clinical
      neuropsychological, physical and psychiatric examination. Imaging of the brain
      could be useful in the differential diagnostic work-up. In mild cases and cases
      of suspected dementia, the work-up is carried out in specialist health care.
      Moderate and severe cases are assessed on primary care. There is currently no
      cure for dementia disorders, although acetylcholinesterase inhibitors may prove
      effective for Alzheimer's disease and Lewy body dementia. Behavioural and
      psychiatric symptoms can be pharmacologically treated. INTERPRETATION: A careful
      diagnostic work-up must be carried out to diagnose dementia. Symptomatic
      treatment is available and should be initiated.

PMID- 11961984
TI  - [Dementia with Lewy bodies].
AB  - BACKGROUND: Some 10%-15% of patients with dementia are diagnosed as dementia with
      Lewy bodies (DLB), a disorder characterised by the presence of Lewy bodies in the
      brainstem and cortex. MATERIAL AND METHODS: Review of pathology, clinical
      symptoms, pharmacological and nonpharmacological treatment, based on the
      literature and on personal experience. RESULTS: Neurochemical findings are marked
      cortical reduction of acetylcholine and nigrostriatal dopamine deficiency. Key
      features of the clinical syndrome are dementia, fluctuating consciousness, visual
      hallucinations and parkinsonism. There are pathological and clinical overlaps
      between DLB and Alzheimer's disease on the one hand, and between DLB and
      Parkinson's disease on the other; the relationship between these diseases awaits
      further elucidation. Clinical consensus criteria for DLB have been published and
      shown to have high sensitivity and specificity. Fluctuating consciousness may be
      difficult to detect, but diagnostic instruments exist that may help in the
      evaluation. Drug treatment of DLB is difficult. Cholinesterase inhibitors have
      been shown to improve cognition and psychiatric symptoms. Atypical antipsychotics
      may improve psychosis, but some patients develop severe sensitivity reactions.
      The effect of antiparkinson agents is unknown.

PMID- 11961986
TI  - [Ventilation of operating rooms].

PMID- 11961985
TI  - [Genetic aspects of Alzheimer disease].
AB  - BACKGROUND: To supply relevant information about the genetics of Alzheimer's
      disease. MATERIALS AND METHODS: Data from the literature (Medline) and personal
      experiences. RESULTS: Two well-known risks for developing Alzheimer's disease are
      established: advanced age and genetic factors. Mutations linked to autosomal
      dominant familial Alzheimer's disease are known in chromosomes 21, 14 and 1. A
      non-mendelian Alzheimer's disease with complex aetiology is linked to the
      apolipoprotein E in chromosome 19. INTERPRETATION: Children of patients with
      Alzheimer's disease have a three to four fold increased risk of developing the
      disease compared to a person without a parent with Alzheimer's disease. The
      diagnostic benefit of apolipoprotein E genotyping is still uncertain.

PMID- 11961987
TI  - [Does organized mammographic screening reduce the breast cancer mortality?].

PMID- 11961988
TI  - Ticking of a time bomb.

PMID- 11961989
TI  - Advances in endocrinology and metabolic medicine.

PMID- 11961990
TI  - How to prescribe hypoglycaemic agents.

PMID- 11961991
TI  - Differential diagnosis of neck lumps.

PMID- 11961992
TI  - Diagnosing gouty arthritis.

PMID- 11961993
TI  - Management of nodular thyroid disease.

PMID- 11961994
TI  - Understanding migraine in women.

PMID- 11961995
TI  - Planning for life beyond the MRCGP.

PMID- 11961997
TI  - [Herbicides and congenital malformations in Meta, Colombia].
AB  - In this paper is presented an statistical study realized upon the duplicated rate
      of congenital malformations per 100,000 inhabitants observed in the district of
      Meta in the last ten years term, which has increased from 99, in 1985, till 189,
      in 1995, coincidentally with the massive country fumigations, with herbicides, as
      Paraquant or Glycofosfate. Other factors such an insufficient nourishment with
      hypovitaminosis B, alcoholism, tobacco addiction, etc., working isolate or
      jointly, are contemplated. Also are taken into account links between these
      factors and the corresponding pathologies. The AA. set out the biochemical
      process from which B vitamin deficiency with energetic ATP depletion trigger a
      cascade of reactions with release of free radicals and PAF, among other
      responses. Weedkillers block vitamin B coenzymes in Krebs cycle. Free radicals
      brake the H links of DNA chromosomes of both spermatozoon and ovule, carrying
      genetic malformations in descendents. And the same if acting metabollically in
      embrionary state because the reduction of acetylcoline synthese and consequently
      failure of vascular system and tissue development. Or directly inflammatory in
      the cell for virus, alcohol, etc.

PMID- 11961998
TI  - [Traumatic cervical subcutaneous emphysema in children].
AB  - Neck emphysema is an unusual pathology in childhood depending on several
      conditions. We report the case of a subcutaneous emphysema of the neck after an
      oropharyngeal injury in a child and take the advantage of the event in order to
      review the etiology and pathogeny of neck emphysema, because the otolaryngologist
      must know the differential diagnosis, face to the presence of air inside the
      neck, since the definitive treatment depends on is etiology.

PMID- 11961999
TI  - [Childhood nasal sinus mucoceles. Review and report of a new case].
AB  - The appearance of mucoceles of paranasal sinuses during infancy is very rare. In
      relation with a patient, 11-year-old, enduring an ethmoidal mucocele treated in
      our Department we benefit it in order to realize a review of the published cases
      in medical literature. We also discuss on the etiopathogenesis, clinic and
      differential diagnostic aspects in pediatric age in comparison of those verified
      in grown-up.

PMID- 11962000
TI  - [Schwannoma of the cervical sympathetic chain].
AB  - Schwannomas are benign tumors of neural source produced from Schwann cells, which
      are the constituents and the maintenance of myelin sheath of peripheral nerves.
      Parapharyngeal schwannoma are sporadic and vagus nerve the one more frequently
      giving raise to parapharyngeal schwannoma. Those originated in sympathetic neck
      chain are more rare. We inform about a parapharyngeal schwannoma case of the neck
      sympathetic chain and perform an analyse of clinic, diagnostical, histological
      and therapeutical characteristics of this so infrequent pathology.

PMID- 11962001
TI  - [Giant cholesteatoma of the external ear canal after myringoplasty].
AB  - Cholesteatoma are specially localized in middle ear and mastoid process, although
      sometimes is the external ear canal which shows the disorder. Usually its a
      appearance is spontaneous. We report a rare case of gigantic cholesteatoma which
      origin was the previous otologic surgery done because of the inclusion of a bit
      of epithelial tissue inside the surgical incision. Similar outcomes justify
      periodical checking after ear surgery with outlining a tympanomeatal flap.

PMID- 11962002
TI  - [Myoepithelioma of the parotid gland].
AB  - Myoepithelioma of the salivary gland is a benign tumor set up almost exclusively
      for myoepithelial cells. It is considered as the terminal form of the
      histopathologic spectrum of mixed tumors, but owing to its monomorphic appearance
      is considered an aside form. In this article is reported one myoepithelial case
      of the parotid gland and are also reviewed the published literature of this sort
      of neoplasms.

PMID- 11962003
TI  - [Paget disease of maxillofacial localization. Clinical case and review of the
      literature].
AB  - Paget's disease is a chronic osteopathy of unknown origin affecting principally
      the long bones of body. One of those cases is here reported localized in this
      area, with favorable answer to medical treatment. Perusal of literature about
      this subject.

PMID- 11962004
TI  - [Diagnostic evaluation of nasopharyngeal carcinoma: role of Epstein-Barr virus].
AB  - We present a retrospective series of 27 nasopharyngeal carcinomas, selected from
      those attended at Ramon y Cajal Hospital between 1977 and 1996, with the aim of
      review the role of the study of Epstein-Barr virus in the diagnostic process of
      nasopharyngeal carcinoma. Twenty-seven patients, ranging from 14 to 81 years,
      with an average age of 50 years were selected. Male/female ratio was 1,7. All but
      one case were Caucasian. A neck mass was the first symptom in 40% of cases, with
      a mean diagnostic delay of 17 months. Only 8 cases (23%) did not exhibit neck
      nodes at the moment of diagnosis. CT and MRI were essential to establish staging:
      5 stage I, 7 stage II and 15 stage IV, due to regional extension and/or bone
      erosion. Radiotherapy was employed in all cases, helped by chemotherapy in 20% of
      them. With a mean follow-up of 62 months, 5-years survival was 32% (IC 14,06
      52,09). Of 27 cases of nasopharyngeal carcinoma 4 were differentiated (type I), 2
      moderately differentiated (type II) and 22 undifferentiated (type III). While LMP
      1 was only expressed by 41% of cases, PCR detected Epstein-Barr virus genome in
      26 cases (96%) and in situ hybridization for EBERs was positive in all cases.
      Thus, all nasopharyngeal carcinomas were related to Epstein-Barr virus.
      Expression of LMP-1 seemed to worse the prognosis of nasopharyngeal carcinoma.

PMID- 11962005
TI  - [Five experts interviewed about drugs. Benefits for the patients could have been
      more emphasized].

PMID- 11962006
TI  - [A new report on osteoporosis coming soon. The SBU evaluates prevention,
      diagnosis and treatment].

PMID- 11962007
TI  - [Primary health care should take the initiative in fighting osteoporosis].

PMID- 11962008
TI  - [Percutaneous vertebroplasty--a new method for alleviation of back pain].
AB  - Percutaneous vertebroplasty (PV) is an interventional radiological procedure for
      the treatment of pain in patients with vertebral compressions caused by
      osteoporosis, metastases or hemangioma. The method was introduced by Professors P
      Galibert and H Deramond at the University Hospital of Amiens, France in 1984. It
      consists of percutaneous injection of bone cement (polymethylmethacrylate) into
      the vertebral body under fluoroscopy guidance. PV has proved to be effective and
      safe. Permanent complete or partial pain relief is obtained within hours or days
      in more than 90% of cases. The complication rate is low, less than 3% for
      patients with osteoporosis and up to 10% in patients with metastases. We report
      on the first 17 patients (11 with osteoporosis, 3 with metastases and 3 with
      hemangiomas) treated in Sweden at the Department of Interventional
      Neuroradiology, Sahlgrenska Hospital, Goteborg University. We obtained complete
      pain relief in 71% and partial pain relief in 17% of cases. The majority of the
      patients improved in mobility and quality of life. We had no clinical
      complications.

PMID- 11962009
TI  - [Too many unnecessary appendectomies. Leukocyte count and CRP value for safer
      diagnosis].
AB  - The increase in leucocyte count is a very early marker of appendiceal
      inflammation, whereas CRP increases are usually seen only after protracted
      inflammation such as appendiceal perforation or abscess formation. Acute
      appendicitis is unlikely in adult patients with normal leucocyte count and CRP
      value, even if clinical symptoms and signs indicate acute appendicitis. However,
      a normal leucocyte count and CRP value do not effectively exclude appendicitis in
      children.

PMID- 11962010
TI  - [Changed thyroxine requirement after sex hormone therapy].

PMID- 11962011
TI  - [Cooperation reduces the risks of thyroid disease in pregnancy. Also mild
      maternal hypothyroidism can threaten the neurological development of the fetus].
AB  - A history of thyroidal disease in a pregnant mother requires special attention.
      Untreated, or not adequately treated, hypothyreosis in a pregnant mother is
      likely to affect the neurological development of the fetus negatively. The
      authors refer the discussion on the need for screening for hypothyroidism in
      early pregnancy, but stress the need for everybody dealing with these patients
      (general practitioners, midwives, gynecologists, pediatricians and
      endocrinologists), to recognize women at risk and inform their patients on the
      need of careful monitoring of thyroid supplementation in case of pregnancy. On
      the other hand, women with Graves' disease should be carefully assessed for the
      presence of TRAK-antibodies, and be subject to specialist maternal care. Their
      babies risk neonatal thyreotoxicosis and need careful attention.

PMID- 11962012
TI  - [Neglected investigations of infertile men. The decreasing sperm count is
      alarming].

PMID- 11962013
TI  - [Angiology is the basis of the diagnostic panorama in internal medicine].

PMID- 11962014
TI  - [A case report. Well-functioning patient care continuity in acute coronary
      syndrome is necessary].

PMID- 11962015
TI  - [Better drug management can improve public health--a study of possible drug
      interactions by scrutinizing prescriptions dispensing by pharmacies].

PMID- 11962016
TI  - [Are physicians blind when it comes to their own health?].

PMID- 11962017
TI  - [Specialists education in the USA: increasing subspecialization and long working
      hours].

PMID- 11962018
TI  - [A dean who started private practice with electrotherapy].

PMID- 11962019
TI  - [Mammographic screening should not be affected by unfounded arguments].

PMID- 11962020
TI  - [Mind meets brain--arguments for the compulsory psychotherapeutic training].

PMID- 11962021
TI  - [Somatization--a significant reality!].

PMID- 11962022
TI  - [Somatization--more a description than an explanation].

PMID- 11962023
TI  - [A too optimistic report of a new study on statins].

PMID- 11962024
TI  - [The members of the HSAN are not isolated in their ivory tower].

PMID- 11962025
TI  - [Where is the evidence concerning the effect of psychotherapy in fatigue
      depression?].

PMID- 11962026
TI  - RCN finances. Stand and deliver.

PMID- 11962027
TI  - Child protection. A little girl failed by the entire system.

PMID- 11962028
TI  - Multiple sclerosis. The long wait for legal cannabis.

PMID- 11962029
TI  - Is nurses' expanded role helping the government, not patients?

PMID- 11962030
TI  - Have skills: will return.

PMID- 11962031
TI  - A beef with the bullies.

PMID- 11962032
TI  - Learning to live with children.

PMID- 11962033
TI  - Pregnant with possibility.

PMID- 11962034
TI  - In the dark? Try light relief.

PMID- 11962035
TI  - Torn: which is the best union for HCAs?

PMID- 11962036
TI  - Bridges, bins, bushes: one nurse's daily beat.

PMID- 11962038
TI  - Tackling the risks of infusion devices.

PMID- 11962037
TI  - Standard of care. Surely some mistake.

PMID- 11962039
TI  - Complications of CVCs and their nursing management.

PMID- 11962040
TI  - Registering reform in mental health.

PMID- 11962041
TI  - Getting to grips with the metal ear syringe.

PMID- 11962042
TI  - Patients with immunodeficiencies regularly attend for immunoglobulin infusions.

PMID- 11962044
TI  - Stoma care--5(b). Problem-solving.

PMID- 11962043
TI  - Dieting to reduce body weight for controlling hypertension in adults.

PMID- 11962045
TI  - Fit for practice. 5.3: Consent and confidentiality.

PMID- 11962046
TI  - Elderly care. UK patients to get remote care by US nurses.

PMID- 11962047
TI  - Workplace hazards. Campaign to reduce sharps injuries toll.

PMID- 11962048
TI  - Continence care is not the weakest link.

PMID- 11962050
TI  - Police inquiry. Nurse arrested following patient's death.

PMID- 11962049
TI  - Management of encopresis and the parents' role.

PMID- 11962051
TI  - Looking good and feeling good: clothes to help promote continence.

PMID- 11962052
TI  - How the continence care guidelines are being implemented.

PMID- 11962053
TI  - Parkinson's disease and the nurse's role in continence assessment.

PMID- 11962054
TI  - Intermittent self-catheterisation.

PMID- 11962055
TI  - Cannabis. CPHVA calls for dope legalisation.

PMID- 11962056
TI  - Review of catheter care guidelines.

PMID- 11962057
TI  - Lower urinary tract symptoms: why incidence rates are vital.

PMID- 11962058
TI  - Learning disabilities. Mencap report slams shortage of school nurses.

PMID- 11962059
TI  - Visit to China--a British perspective.

PMID- 11962060
TI  - Osteoporosis: important knowledge for the ophthalmic healthcare provider.

PMID- 11962061
TI  - Happiness at work: it's an inside job!

PMID- 11962063
TI  - Accurate documentation equals quality patient care.
AB  - Accurate nursing documentation has a central role in both quality care and
      revenue issues facing hospitals today. However, it is often difficult to complete
      documentation when nurses are faced with the completion of multiple care issues.
      This problem is no more evident than in the operating room. Comprehensive
      documentation requires not only time and effort on the nurse's part, but a
      dedication and belief in its imperative. Nurses must always keep in mind that the
      "results and benefits of nursing documentation are greater than the sum of the
      task itself. Documentation IS quality patient care".

PMID- 11962062
TI  - The age-related eye disease study: the results of the clinical trial.
AB  - The Age-Related Eye Disease Study (AREDS) is a multi-center study sponsored by
      the National Eye Institute to determine the natural history and risk factors
      associated with both cataract and age-related macular degeneration (AMD). AREDS
      incorporated a clinical trial to determine what role micro nutrients may play in
      the development and progression of cataracts and AMD. The micro nutrients studied
      were the antioxidants vitamins E,C, beta-carotene and zinc with copper.
      Participants were randomized to either antioxidants, mineral, a combination of
      antioxidants and minerals or placebo. The participants were categorized, by the
      presence of drusen and diagnosis of AMD into one of four groups: no AMD, early
      AMD, intermediate AMD or advanced AMD. They were followed for an average of 6.3
      years. There was no statistically significant difference in the cataract trial
      between treatment and placebo. In the AMD trial groups, those at high risk of
      developing advanced AMD lowered their risk by about 25% when treated with the
      mega dosages of the combination of antioxidants and minerals.

PMID- 11962064
TI  - An evaluation of all-in-one incontinence pads.

PMID- 11962065
TI  - Treating diarrhoea and constipation.

PMID- 11962066
TI  - How to administer enemas and suppositories.

PMID- 11962067
TI  - Bowel management and consent.

PMID- 11962068
TI  - The goal of medical imaging.

PMID- 11962069
TI  - Six Sigma gains momentum in healthcare.

PMID- 11962070
TI  - Credentialing to be required for Medicare reimbursement.

PMID- 11962071
TI  - Trust me, you will land another job.

PMID- 11962072
TI  - New realities shape future radiology delivery models.
AB  - Unlike many changes taking place in diagnostic imaging, the movement to find
      alternative reading sites is not primarily technology driven. The technology
      necessary to accomplish remote reading has been available for more than 20 years.
      The relatively recent enhancement of such technology has made remote reading much
      more practical and more clinically reliable than in the past. Indeed, without
      these upgrades, remote reading would be impossible. However, the real impetus for
      its use comes from the unprecedented staffing shortages taking place in radiology
      today. How bad is the shortage? Projections by U.S. Radiology Partners (USRP)
      show that even if radiologists practiced until they were 70 years old, and
      volumes remained at current levels, it would still take five years for supply to
      come into line with demand. Given current trends, the shortage can be expected to
      continue for another eight to 10 years at a minimum. Necessity therefore obliges
      hospitals to rethink old assumptions. One of these assumptions concerns remote
      reading. This alternative has been available for at least 10 years, but rarely
      has been embraced by hospitals. The key to successful radiology management and
      delivery today is to link staff with technology strategically. There are several
      steps necessary to creating a proactive staffing and reading system in tune with
      today's market. These include: establish a professional network, assess your
      technology needs, assess your clinical needs, include referral staff in the
      process, establish clear standards, encourage interaction with remote physicians,
      communicate with patients and involve technologists.

PMID- 11962073
TI  - High-dose fluoroscopy: the administrator's responsibilities.
AB  - During the past 15 years, developments in x-ray technologies have substantially
      improved the ability of practitioners to treat patients using fluoroscopically
      guided interventional techniques. Many of these procedures require a greater use
      of fluoroscopy and serial imaging (cine). This has increased the potential for
      radiation-induced dermatitis, epilation and severe radiation-induced burns to
      patients. Radiology administrators must realize that these high-dose procedures
      increase the risk for radiation injury and radiation-induced cancer in personnel
      as well as in patients. This article discusses particular clinical cases and
      describes positive, pro-active steps that practitioners and administrators can
      take to help prevent such injuries in their facilities. Unfortunately, with the
      exception of radiologists, a large proportion of physicians who use fluoroscopy
      have effectively no training or credentials in management of radiation or the
      biological effects associated with its use. In 1994, an FDA advisory warned that
      training of physicians for modern-day use of the fluoroscope was for the most
      part insufficient and needed to be expanded. Many prominent medical organizations
      such as the American College of Cardiology (14) and the American Heart
      Association (15) have published strongly worded position papers agreeing that
      there is an urgent need for such training. The consensus is that "rubber-stamp"
      privileges (16,17) to perform fluoroscopic procedures should no longer be
      granted. At present, the JCAHO is considering the implementation of a statement
      regarding JCAHO standards and privileges for practitioners to use fluoroscopic x
      ray equipment. Whether or not the JCAHO becomes involved, it is becoming
      increasingly clear that all practitioners who use fluoroscopic radiation should
      be required to complete focused training in radiation physics, radiation biology
      and radiation safety. Training should include the pertinent aspects of radiation
      management in the clinical setting so that these physicians will be able to
      acceptably control risks to patients and personnel. The task of securing these
      materials and lecturers and documenting everything may fall on the shoulders of
      the radiology administrator or radiation safety staff. Completion of an approved
      educational program (with appropriate testing) provides the evidence needed by
      the facility to approve the practitioner's qualifications. In summary, it will
      take a concerted effort on the part of professional medical organizations and
      regulatory agencies to insure that the wealth of preventative information now
      available is disseminated to and put to use by these physicians who may fail to
      fully appreciate the potential for imparting serious injury to their patients.
      Even one radiation injury caused by lack of education is unacceptable.

PMID- 11962074
TI  - Proposed: improve efficiency, reimbursement and LOS through better utilization of
      inpatient imaging procedures.
AB  - In recent years, most hospitals have gone through several rounds of cost cutting
      initiatives. While it is necessary and prudent to closely monitor operating costs
      and staff utilization, the focus needs to shift from cutting cost to increasing
      revenue. This study examines the potential financial benefit of performing
      diagnostic imaging procedures that are ordered on inpatients the day of, or the
      day prior to discharge as outpatient exams, following discharge. While this
      analysis focuses on revenue enhancement, it will not lose site of the fact that
      patient safety and quality clinical care always come first. We selected three
      imaging modalities for study: CT, MR and nuclear cardiology. These modalities are
      unique because of their expensive nature, length of time to complete, and limited
      availability. Also, they typically yield the highest reimbursement per procedure
      when compared to other diagnostic imaging procedures. Yearly volume at North
      Shore University Hospital for CT, MR and nuclear cardiology studies performed on
      the day of or day before discharge is projected to be 1,120 studies. Sixty-two
      percent of the total is generated by nuclear stress tests, 34 percent by CT, and
      only 6 percent is related to MR. On an annual basis, approximately $840,800 in
      hospital charges will be generated for inpatient procedures performed on the day
      of or one day before discharge. Implementing change is a difficult and
      complicated process. The following are among many factors that must be carefully
      considered: physician education, consensus building, patient care guidelines,
      ongoing performance improvement activities and scheduling. This study focused on
      a small aspect of inpatient procedure utilization and identified reimbursement to
      the hospital. The most significant finding of this project relates to the fact
      that of the 323 CT and MR studies performed, 83 percent of the findings were
      positive, and the patients were still discharged. That fact further supports the
      concept of performing studies ordered on the day of or one day prior to discharge
      as outpatient procedures.

PMID- 11962075
TI  - Meeting the challenge of continuing education with eLearning.
AB  - For many of us, the concept of "e" anything invokes a sense of skepticism and
      even dread. However, the Web and all it has to offer is certainly an integral
      part of modern life and, once reconciled, offers great opportunities for commerce
      and knowledge building. One particular area of promise is that of online learning
      or "eLearning" as it is referred to in the literature. Particularly for
      sonographers and technologists, the ability to travel to seminars and conferences
      on hospital budgets and time is a distant memory. Conversely, the pressure to
      stay current with CE requirements is greater than ever. With the growing
      phenomena of accreditation and the use of that as standard for quality care,
      these staff members are under more pressure than ever to maintain their
      certification. There is also the issue of accountability. What is being done to
      track employee training and assist in on-going development? How do we know that
      the program was appropriate for that particular employee and that an adequate ROI
      was achieved from a learning perspective? With eLearning, the opportunity to
      track the employee's progress, scores and areas of interest are possible. This
      can assist the administrator in "managing" the learning within the group and
      taking an active role in the development of the staff. The ultimate eLearning
      experience provides the right content at the right time. It motivates people to
      learn and apply their knowledge and skills to improve their individual and
      organizational performance. This is achieved by providing learners with easy and
      immediate access to the content. The design elements of the site should include a
      friendly format that facilitates easy navigation through the content. Other
      helpful features are: book-marking that allows the student to return to the last
      page studied, interactivity, visualization technologies, and feedback throughout
      the learning experience. The opportunities for the utilization of eLearning in
      the global medical community are remarkable. eLearning facilitates learning at
      anytime and anywhere. It reduces the obstacles of time and distance, providing
      greater equality of opportunity.

PMID- 11962076
TI  - The persuasive administrator.
AB  - The art of being persuasive involves use of selected persuasive techniques
      appropriate to the individual and situation. Persuasive techniques are powerful
      tools of communication and productivity. Effective use of persuasive techniques
      can provide motivation to others and can mobilize them toward action that you, as
      an administrator, desire.

PMID- 11962077
TI  - The length of certification examinations.
AB  - The AHRA CRA examination development process is based on the sampling plan (or
      test blueprint) developed from the role delineation study implemented in 2001.
      Panels of radiology administration experts have written and validated multiple
      choice questions and assembled the first version in accordance with the test
      blueprint. The number of questions in each domain is listed in Table 2.

PMID- 11962078
TI  - Trust your mother, but get it in writing.

PMID- 11962079
TI  - Women and depression: not just "the blues".

PMID- 11962080
TI  - Strong bones for life.

PMID- 11962081
TI  - Needlestick update.

PMID- 11962082
TI  - Clinical workforce shortage. Healthcare's most important challenge.

PMID- 11962083
TI  - Nursing in the new millenium.

PMID- 11962084
TI  - [Effects of nitric oxide donor SIN-1 on calcium transport in rat cardiac
      sarcoplasmic reticulum].
AB  - The effects of non-enzymatic disintegration of SIN-1 products (nitric oxide,
      superoxide anion and peroxynitrite) on Ca(2+)-transport of sarcoplasmic reticulum
      were studied on homogenates of rats myocardium. It was shown that SIN-1 (30
      microM) exerts a significant activating effect on ryanodine-sensitive calcium
      channels resulted in three-fold increase of Ca2+ release rate via these channels.
      Such effect of SIN-1 realized mainly by nitric oxide effect and, partially,
      superoxide radical. SIN-1 did not effect the Ca(2+)-ATPase activity of
      sarcoplasmic reticulum.

PMID- 11962085
TI  - The effect of Psilocybe cubensis extract on hippocampal neurons in vitro.
AB  - The action of P. cubensis mushroom extract, containing psilocybin (PCB) and
      psilocin, on spike activity of hippocampal CA1 pyramidal neurons was studied in
      in vitro rat brain slices. In 38 (76%) out of 50 investigated neurons spike
      activity was decreased, in 2 (4%) cells it increased. There was no response 10
      (20%) neurons. Application of the extract caused short burst firing in 12 (24%)
      neurons. All neurons showing inhibition during PCB-containing extract
      application, were also inhibited by serotonin (5-HT). Usually inhibitory reaction
      did not last over 4-5 min upon 3 min extract application and could be prolonged
      up to 10-43 min up on serotonin application. Part of neurons were inhibited by
      serotonin and did not react to extract application. Inhibitory reactions induced
      by extract application were blocked by ritanserin in half of the tested units and
      were induced due to activation of 5-HT2 serotonin receptors. The extract
      suppressed excitative spike reactions caused by application of L-glutamic acid.
      It is concluded, that application of PCB-containing extract in most cases reduced
      spike activity in hippocampal CA1 pyramidal neurons and suppressed glutamate
      transmission.

PMID- 11962086
TI  - [Activity of elastase and its inhibitors in tissues of aorta and blood serum in
      various types of acidosis].
AB  - In modeling of different types of acidosis (hyperchloraemic, lactate and
      ketoacidosis in the starvation) at rats the elastase activity, contents of alpha
      2 macroglobulin (alpha 2M) and alpha-1 proteinase inhibitor (alpha 1PI) in aorta
      tissues and blood serum were studied. The obtained results indicate that the
      degree of disturbance in system elastase-inhibitors depends on expressiveness of
      parameters changes in system of acid-base state regulation. In modeling of
      various types of acidosis coefficient inhibitors/elastase is reduced due to
      different parameters change in aorta, namely decrease of alpha 2M contents--in
      hyperchloraemic acidosis, increase of elastase activity--in lactat-acidosis,
      increase of elastase activity and decrease of alpha 2M contents--in ketoacidosis.
      In blood serum the similar coefficient is reduced due to increase of elastase
      activity and decrease of alpha 2M contents in hyperchloraemic acidosis and
      starvation, and, in turn, due to decrease of alpha 2M contents--in lactat
      acidosis. The obtained data indicate that one of mechanisms of vascular wall
      damage in acidosis is disturbance of balance between elastase and its inhibitors
      in tissues of arteries.

PMID- 11962087
TI  - [The effect of cyclic nucleotides on the membrane potential of intact endothelium
      of isolated rabbit aorta].
AB  - The influence of intracellular cyclic nucleotides concentration increase on the
      membrane potential of intact endothelium of isolated rabbit aorta has been
      investigated. Both applications of bucladesine, an adenosine 3',5'-cyclic
      monophosphate (cAMP) membrane permeable analogue, and phoshophodiesterase
      blockers 3-isobutyl-1-methylxanthine (IBMX) and theophylline depolarized
      endothelial membrane. IBMX-induced depolarization was significantly smaller then
      theophylline-induced depolarization. It could be explained by the existence of
      IBMX-insensitive phosphodiesterases. Non-selective protein kinase blocker H-7 did
      not affect on the both IBMX-stimulated and non-stimulated membrane potential of
      aortic endothelium. It has been shown that the IBMX-induced depolarization and
      ATP-induced depolarization correlate with high correlation coefficient.

PMID- 11962088
TI  - [Nucleic acid and protein content in rat prostate during combined treatment with
      the gonadorelin agonist and an androgen receptor inhibitor].
AB  - The effects of androgen receptor blocker Flutamide (Niftolide) and/or LH
      releasing hormone agonist Surfagon on the nucleic acids and protein contents in
      the ventral prostate of male rats were studied. It was shown that combined drug
      treatment led to potentiating of "antiprostatic" effects of both preparations
      resulted in significant decrease of DNA, RNA and protein contents.

PMID- 11962089
TI  - [Effect of low intensity electromagnetic radiation on coagulation and
      fibrinolytic properties of blood in vitro].
AB  - It is shown that new hypotheses concerning the mechanism of low-intensity mm-wave
      radiation effect on plasma and thrombosis haemocoagulation and fibrinolitic
      system. It is supposed that plasma and thrombosis factors in the area of
      irradiation can be primary receptor that transfer external radiation onto primary
      physiological targets.

PMID- 11962090
TI  - [Pharmacological analysis of the antihypoxic action of aminobutyric acid
      derivatives].
AB  - The correlation-regressive and pharmacological analysis of butane acid derivates-
      ufibrat, Re2(isoC3H7COO)4Cl2Ta[Re2(GABA)2Cl4(H2O)2]Cl2--was made. It is
      established that among these substances antihypoxic activity on the hypercapnic
      hypoxic hypoxia have only ufibrat. It decrease mice's temperature of body,
      increase duration of period to the appearance of sudoms and the life
      longitudindity at the condition of hypercapnia-hypoxia.

PMID- 11962091
TI  - [Oxidative and antioxidative status of mother-fetus system in swine].
AB  - Lipids peroxidation and the antioxidation defence in a liver, myometrium,
      endometrium of sows second half gestation, and also in foetal membranes and liver
      of foetuses was studied. The increase in peroxidation processes in the tissues of
      the uterus during the 3rd month of gestation was ascertained. The local
      influencing of foetuses on dynamics of studied processes in a wall of a uterus
      fixed depending, what is displayed in intensification of lipids peroxidation with
      increase in the antioxidation defence of the same time.

PMID- 11962092
TI  - [Changes in the levels of non-enzymatic cationic proteins and degree of damage in
      leukocytes in rabbits with hemorrhage].
AB  - We study the contain of non-enzymatic cationic proteins (NCP) and the "degree of
      damage" in leucocytes in the rabbits with hemorrhages. In the animals with
      unimportant hemorrhages the contain of NCP in leucocytes increased. But in the
      rabbits with the considerable and return hemorrhages the contain of NCP in
      leucocytes lost. The degree of damage in leucocytes increased in the all
      experiments. The received results proved the presence of leucocytolysis in the
      rabbits with considerable and return haemorrages. In the rabbits with hemorrhages
      the contain of NCP in leucocytes changed dependence of the weight of the
      hemorrhages.

PMID- 11962093
TI  - [The protective effect of anti-Pseudomonas blood preparations].
AB  - Human blood antipseudomonas preparation activity has been studied on the model of
      Ps. Aeruginosa etiology sepsis in white not pedigree mice. It has been found out
      that antipseudomonas plasma and antipseudomonas immunoglobulin with antibody tire
      1:80 possess marked therapeutic properties. The obtained results of the
      experimental studies are the grounds for clinical studies carrying out with the
      use of blood antipseudomonas preparations in combined therapy of the patients
      with diseases of Ps. Aeruginosa etiology.

PMID- 11962094
TI  - [Dynamics of blood proteins spectra in normal and diarrheic long horn cattle
      during early ontogenesis].
AB  - The contains of blood plasma protein fractions and immunoglobulines were studied
      in adult cattle and in new born calves (just new born and age of 1, 2, 5 and 10
      days) by the 10% PAAG EP (0.1% SDS) and radial immunodiffusion methods. It is
      shown that protein bands of 140-160 kD and immunoglobulines (G1, G2, M) are
      absent at the moment of birth. The physiology level of gamma-globulines and IgG1
      reach at 1 day of life, while IgM--at second. After colostrum breeding of just
      new born calves the speed increasing of total plasma protein and gamma-globulines
      fraction are lowest (in 2.7 and 1.7 times respectively) in diarrhoea animals in
      compare to the health one. The maximum level of IgG1 concentration forms in
      disease animals only at 10 days of age. On the date obtained it is concluded the
      presence such new born calves which have low level of small intestine developing
      and disturbance of immunoglobulines absorption.

PMID- 11962095
TI  - [Quantitative evaluation of the psychophysiological state of a person upon
      successful completion of work].
AB  - Ability of prediction successfulness of done work by the self-organizing maps was
      shown. Mathematical model which may be to appraise successfulness of done work by
      time of reaction on light signal and speed treat information was built. This
      model may be used for the estimate of the psychophysiological condition in the
      process of activity.

PMID- 11962097
TI  - [Mechanisms of generating calcium signals in exocrine acinar cells].
AB  - Review. Modern data about mechanisms of generation of the calcium signals in the
      exocrine acinar cells are presented. The mechanisms of inositol-1,4,5
      trisphosphate- and Ca(2+)-induced Ca2+ release from intracellular stores of the
      acinar cells and mechanisms their influx from extracellular medium are described.
      The mechanisms which initiate Ca2+ oscillations and their role in the secretion
      of the fluid and enzymes by acinar cells are discussed.

PMID- 11962096
TI  - [The role of gamma-delta T-lymphocyte subtypes in normal and pathologic
      conditions].
AB  - In the review data about origin, spreading in the organism, differentiation,
      physiologic sense, role in diversity of pathologic processes, and also pharmaco-
      and immunocorrection's probable foundations of T-lymphocyte's new population with
      T cell receptor (TcR) gamma delta (TL gamma delta) are resumed. In the
      phylogenesis TL gamma delta are supposed to be older than T lymphocytes with TcR
      alpha beta. The conclusion is based upon domination of this lymphocyte population
      at gestation's early stage and huge representation of pseudogenes in the DNA
      region that encodes TcR structure of TL gamma delta. A morphological and
      functional resemblance of the given population with natural killer cells is
      underlined. It is paid attention to wide representation of TL gamma delta in the
      periphery tissues, poverty of TcR diapason that may evidence about
      postdifferentiation's process of TL gamma delta to be accomplished due to TcR
      genes rearrangement. This process appears to supply the enhancement of antigen
      specific TL gamma delta in foreign agent's inculcation. A maturation process and
      probable mechanisms of these lymphocytes education in thymus is described. A
      classification of TL gamma delta depending on TcR structure and cytokine profile
      of the lymphocytes that subdivides them on T-helper/cytotoxic (Vg9/Vd2 phenotype)
      and cytotoxic/suppressor (Vd1 or Vd3 phenotype) was proposed. In the review the
      role of TL gamma delta in mucous immunity supporting and possible participating
      in systemic regulation of the immune response is emphasized. A physiologic role
      of TL gamma delta, namely ability to identify non-protein antigens
      (lipopolysaccharides, polyphosphates, glycolipids) and heat shock proteins, is
      also described. Evidences about uncertainty of incomplete phagocytosis phenomenon
      in vivo in case of TL gamma delta's normal function are given. Particularly it is
      made out that these lymphocytes are able to activate inducible NO-synthase in the
      macrophages that enhances their phagocytic activity in tens time. A function of
      these lymphocytes in defense against infection of bacterial, viral, protozoa,
      fungal origin, and also in tumor growth and autoimmune diseases is represented.
      Methods of specific therapeutic influence upon TL gamma delta, both
      pharmacological (pamidronat, 2,3-diphosphoglyceric acid) and immunologic profile
      (monoclonal antibodies conjugated with cytotoxic agent) are given.

PMID- 11962098
TI  - Forgiveness: origins, dynamics, psychopathology, and technical relevance.
AB  - This paper integrates a diverse and scattered literature to describe the
      psychodynamic underpinnings of granting and seeking forgiveness. The evolutionary
      foundations and the developmental substrate of these capacities are elucidated.
      An individual who fails to make certain intrapsychic achievements may be
      vulnerable to psychopathological development, as is evident in those who cannot
      forgive or forgive too readily, constantly or never seek others' forgiveness,
      cannot accept forgiveness, or show an imbalance between their capacities to
      forgive themselves and to forgive others. The relevance of various developmental
      and phenomenological concepts to psychoanalytic technique, including the
      patient's need to forgive and to be forgiven, is also discussed.

PMID- 11962099
TI  - Flaubert's Madame Bovary: a study in envy and revenge.
AB  - Flaubert's Emma Bovary is one of the most convincingly realized characters in
      modern literature. Her husband, Charles, a rural doctor, loves her dearly, but he
      is dull, ineffectual, and boring. Emma seems to hate him with a fury that knows
      no bounds. She betrays him sexually, ruins him financially, and ultimately
      destroys his very life. What drives her to such unmitigated rage? The authors
      identify evidence in the novel suggestive of a dynamic thrust for revenge along
      the lines described by Freud (1918) in "The Taboo of Virginity." Elements of
      narcissistic rage and a sense of entitlement intensify Emma's anger and
      vengefulness.

PMID- 11962100
TI  - American pragmatism and American psychoanalysis.
AB  - The author compares American pragmatism with American psychoanalysis in an effort
      to place the existence of the many diverse schools and theories of psychoanalysis
      in a historical context. Pragmatism is seen as a theory of instrumentation or a
      collection of tools for accomplishing goals; it claims that many of our efforts
      to know and seek truth are based upon myths. Psychoanalysis, too, can be seen to
      pursue certain theoretical claims based on myths. The present climate of
      pluralism in psychoanalysis is not a phase, but an indication of our diverse ways
      of achieving in-depth understanding of another person.

PMID- 11962101
TI  - "Enactment" in the lives and treatment of Holocaust survivors' offspring.
AB  - This paper explores an aspect of "enactment" often seen in Holocaust survivors'
      offspring: the compulsion to re-create their parents' experiences in their own
      lives through concrete acts. At the core of this compulsion is a psychic hole, a
      gap in the child's emotional understanding, stemming from identification with the
      parents on one hand, and the parents' denial or repression of the trauma on the
      other. The compulsion to enact can be transformed into a cognitive mode when such
      offspring are helped to find the meaning of the trauma in their parents' lives,
      as is illustrated here by clinical examples.

PMID- 11962102
TI  - The early oedipal situation: developmental, theoretical, and clinical
      implications.
AB  - The Oedipus complex is typically thought to begin in the phallic phase, when the
      child's relationship to the parents as a couple achieves central prominence. In
      contrast, the author views the appearance of oedipal conflicts in the phallic
      phase as the end point of a line of development of triangular relatedness that
      began in infancy. An aspect of the Kleinian view of the oedipal situation--that
      awareness of the parents as a couple begins in the preoedipal period--deserves
      serious consideration. A patient is presented for whom the working through of
      early oedipal issues in the transference-counter-transference permitted recovery
      from withdrawal into a fantasy world.

PMID- 11962103
TI  - Reflections on creative aspects of psychoanalytic diagnosing.
AB  - This paper explores the therapeutic value of considering psychoanalytic diagnoses
      as co-constructions, and emphasizes two interrelated points: First, there are
      distinctions between medical, psychiatric, and psychoanalytic diagnoses, and
      similarly, a distinction may be drawn between diagnoses as nouns and the activity
      of diagnosing. Second, the author stresses that psychoanalytic diagnoses are
      theory bound. Various competing theories facilitate or interfere with the
      maintenance of an optimal analytic attitude. Some theories facilitate an
      analyst's urge to engage in the activity of diagnosing, which may reflect a
      destructive countertransference enactment. Analytic data in support of these
      premises is presented and discussed.

PMID- 11962104
TI  - New endeavours for HIV prevention in the Balkans.

PMID- 11962105
TI  - Hypertension recommendations: are they relevant to public health?

PMID- 11962106
TI  - Globalization and reform of the World Trade Organization.

PMID- 11962107
TI  - Trends of hepatitis B and hepatitis C mortality in Canada, 1979-1997.
AB  - Mortality data from Statistics Canada were analyzed to measure the temporal
      trends and burden of illness attributed to viral hepatitis in Canada. Analysis of
      age-standardized mortality rates from 1979 to 1997 showed an increasing trend in
      mortality for both hepatitis B and non-A, non-B hepatitis (NANBH), most of which
      are attributed to hepatitis C infections. Hepatitis B and NANBH age-standardized
      mortality rates increased respectively, from 0.03 and 0.12 deaths per 100,000
      population in 1979 to 0.26 and 0.41 deaths per 100,000 in 1997. Male mortality
      rates were consistently higher than female for both diseases. Among deaths from
      chronic liver disease, over 1,000 deaths were estimated to have been caused by
      hepatitis B and hepatitis C annually. Although the hepatitis B or NANBH recorded
      deaths largely underestimate the true burden of HBV and HCV in Canada, the
      temporal trends are useful as they reflect changes in the impact of both
      diseases.

PMID- 11962109
TI  - Canadian Incidence Study of Reported Child Abuse and Neglect: methodology.
AB  - This article describes the methodology of the first Canada-wide study of the
      incidence and characteristics of reported child abuse and neglect. Child welfare
      investigators from a random sample of 51 child welfare service areas completed a
      three-page survey form describing the results of 7,672 child maltreatment reports
      received during the months of October to December 1998. The study documented a
      90% participation rate and a 95% item completion rate. An estimated 135,571 child
      maltreatment investigations were completed, a rate of 21.52 investigated children
      per 1,000 children in Canada in 1998. The Canadian Incidence Study of Reported
      Child Abuse and Neglect is a rich database that will provide researchers with
      important contextual information on reported child maltreatment in Canada and a
      comprehensive source of information on factors associated with key service
      decisions made by child welfare investigators.

PMID- 11962108
TI  - Prenatal HIV screening in a tertiary care centre.
AB  - OBJECTIVE: Strategies are available to reduce maternal-fetal transmission of HIV
      and depend on adequate prenatal screening. At present, a significant proportion
      of Canadian pregnant women remain unscreened. We reviewed our screening practices
      before and after the implementation of a departmental policy on universal
      counselling for HIV screening and the distribution of a patient educational
      brochure developed at our centre (interventions). METHODS: Charts of all new
      antenatal patients seen during February-April in 1996 (n = 186) and 1998 (n =
      212) were reviewed. Maternal demographics and evidence of HIV counselling and
      screening were collected and analyzed. RESULTS: Following our interventions, HIV
      counselling and screening rates increased from 13% to 72%. Patient acceptance of
      testing was high. The majority of missed opportunities for HIV testing were
      patients transferred urgently from other institutions. CONCLUSION: HIV
      counselling and screening can be improved by implementation of local strategies.
      We have demonstrated the feasibility of this approach in a tertiary care unit.

PMID- 11962110
TI  - [Coverage rates of the d2T5 vaccine in adolescents up to 15 years of age residing
      in Monteregie].

PMID- 11962111
TI  - [Impact of active research for vaccination information in children with
      incomplete or lost vaccination records].
AB  - We estimated the accuracy of the information in the vaccination booklet of 8,457
      children. The booklets were classified as complete (CC), incomplete (CI) or lost
      (CP). For children in the CI or CP categories, an active search was done in their
      providers' records and we assessed their vaccine coverage. Overall, the booklet
      provided accurate information for 88.6% of the 7,646 children who were vaccinated
      at least once. Among the 711 children in the CI category, the active search
      showed that 79% had received all their vaccines at age two years whereas this
      proportion was 59% among the 280 children in the CP category. The active search
      increased the vaccine coverage in the population by 4%. CONCLUSION: The majority
      of children in the CI or CP categories whose parents report that they received
      all their vaccines are in fact adequately vaccinated.

PMID- 11962112
TI  - [Prematurity and low birth weight: effects of active and passive smoking during
      pregnancy].
AB  - Among the risk factors inevitably associated with low birthweights and premature
      births, tobacco remains the factor most often cited. From 1997 to 1998, a study
      was conducted in a Quebec City hospital centre in order to determine the
      prevalence of smoking among pregnant women as well as their exposure to passive
      smoking at home and at work. The percentage of women who smoke before pregnancy
      is 40.2%, while that of women who smoke during pregnancy is 37.3%. The analysis
      of characteristics of pregnant women who smoke and do not smoke shows strong
      variations according to age, education, matrimonial status and income. The
      relative risk linked to smoking is 1.54 for premature birth and 2.21 for low
      birthweight.

PMID- 11962113
TI  - Characteristics of preterm delivery and low birthweight among 113,994 infants in
      Alberta: 1994-1996.
AB  - This study examined the impact of infant and maternal factors on preterm delivery
      and low birthweight (LBW) in Alberta between January 1, 1994 and December 31,
      1996. Data on 113,994 births were collected from vital statistics registration
      birth data. Logistic regression models for preterm and LBW delivery suggested the
      key risk factors were multiple and still birth (odds ratios > 22.0). Other
      characteristics included female gender, birth defects, nulliparous women,
      maternal age 35 and greater, unmarried, history of abortion, maternal smoking,
      maternal street drug use, and having less than 4 prenatal visits (odds ratios
      0.86-2.54). Interactions between smoking and alcohol, and smoking and parity were
      noted. Efforts to improve the currently low rates (8.2%) of smoking cessation
      during pregnancy are required. Social, economic and medical factors associated
      with delayed childbearing and birth outcomes should be investigated.

PMID- 11962114
TI  - Vitamin-mineral supplementation and use of herbal preparations among community
      living older adults.
AB  - Basic information on seniors' use of supplements is lacking. In this study, a
      convenience sample of community-living older adults (n = 128) was recruited from
      10 sites to determine the prevalence, frequency, duration and type of supplement
      use. Use information, demographics and medical/nutritional history were collected
      with an interview-administered questionnaire. Supplement use included both
      vitamin-mineral and/or herbal preparations. Average age of participants was 76
      years and 73% were female. Users comprised 79.9% of the sample. Vitamin E was the
      most common vitamin-mineral and herbal teas were the most popular herbal
      preparations. The predominant reason for use was to "improve one's health".
      Initial results suggest that older adults are learning about, using and
      purchasing these supplements from a variety of sources. With this common use and
      the concerns over interactions with prescription medications, further work is
      required to determine if these findings are consistent in a more diverse,
      randomly selected older Canadian population.

PMID- 11962115
TI  - Decreasing influenza impact in lodges: 1997-2000 Calgary Regional Health
      Authority.
AB  - Influenza causes high morbidity and hospitalization rates in residents of seniors
      lodges, I causing increased pressure on emergency departments and hospital beds
      every winter. This quasi-experimental study assessed the prevention of influenza
      outbreaks and their consequences in Calgary lodges. A multidisciplinary team
      worked to improve communication between health professionals, increase resident
      and staff immunization coverage, obtain weights and creatinines prior to
      influenza season, and facilitate amantadine prophylaxis during influenza A
      outbreaks. We had an increase in standing orders for amantadine and up to 56% of
      residents from one lodge had documented creatinine levels. Amantadine was
      administered to residents within two days of outbreak notification. Influenza
      morbidity in lodge outbreaks decreased from a rate of 37% to 9% over the three
      years and hospitalization rates decreased from 9% to 1%. We recommend that other
      regions consider a similar approach to decreasing influenza morbidity and
      hospitalization in lodge residents.

PMID- 11962116
TI  - Maclean's rankings of health care indices in Canadian communities, 2000:
      comparisons and statistical contrivance.
AB  - A critical perspective is presented in regard to the 2000 regional rankings of
      Canadian health care indices by Maclean's magazine, June 5, 2000. This
      perspective is related in format to previous analyses of the Maclean's rankings
      of Canadian universities. Several pitfalls in the health care ranking procedures
      are summarized. The Maclean's data and general criteria appear conceptually
      reasonable, but their inconsistencies and limited range, together with problems
      in interpretation of rank data, do not allow them to be logically or empirically
      useful in the matter of health care evaluation, that is, in the manner portrayed
      for readers of Maclean's. Using a particular set of parameters defined as health
      "indicators," the rank data show gratuitously that communities better endowed
      with certain health services, such as those with medical schools, tend to provide
      higher levels of care.

PMID- 11962117
TI  - Characteristics of patients with a regular source of care.
AB  - This study was designed to describe patient characteristics associated with
      having a regular source of care among all patients who received care from large
      urban clinics in Manitoba over a three-year period (N = 298,222). Using
      administrative data, patients were classified as having a regular source of care
      if they made 75% or more of their total ambulatory visits to the same clinic.
      Overall, 44.2% of patients had a regular source of care. A logistic regression
      showed that children and adults aged 45 and older were more likely to have a
      regular source of care than patients aged 18-44. Moreover, patients with a
      regular source of care tended to live in more affluent neighbourhoods and were
      healthier than individuals with no regular source of care. Systemic changes might
      be needed to enhance continuity of care (e.g., mechanisms to enhance access)
      among vulnerable segments of the population like the poor.

PMID- 11962118
TI  - [Evaluation of diffusion of a project for tobacco use reduction].

PMID- 11962120
TI  - [Utilization of technology and communication technologies (TIC) in public
      health].
AB  - The development of information and communications technologies (ICT) and Internet
      offers public health practitioners new tools to fulfill their missions of
      monitoring public health, health promotion and disease prevention, and public
      health protection. In recent years, new applications and practices in public
      health using these technologies have emerged, particularly in the area of
      communication among practitioners and transmission of information to the
      population. This article aims to give an overall view of the use of ICT in public
      health and to discuss the impact of these technologies on public health
      practices. The discussion is centred around the implications of using these new
      technologies: implications with regard to the new possibilities provided by these
      technologies, but also with regard to the difficulties involved in their use as
      well as issues related to unequal access and ethics. Finally, the question of the
      evaluation of these technologies and of their impact on public health is
      discussed.

PMID- 11962119
TI  - Inter-provincial variation in government drug formularies.
AB  - In Canada, coverage for ambulatory prescription drug expenditures is provided to
      some groups by provincial drug plans through a provincial formulary. Little is
      known about the drugs provincial formularies give access to. We report the
      variation in availability of new drug molecules (NDM) across provincial
      formularies. We identified 108 NDM approved in Canada between 1991 and 1998. From
      each drug plan bulletin or formulary, we abstracted names of NDM listed as per 15
      January 1999. We compared the level of listing across provinces using kappa
      coefficients. In the Quebec, BC, Manitoba and Saskatchewan formularies, more than
      70% of the NDM were listed. In four provinces, this proportion was lower than
      50%. In general, the agreement between formularies was poor. There is a wide
      variation across provinces in terms of NDM listed in the formularies. This
      variation reflects inter-provincial differences in the way drugs are selected for
      coverage.

PMID- 11962121
TI  - Achieving cardiovascular health through continuing interprofessional development.
AB  - In order to achieve cardiovascular health for all Canadians, the ACHIC (Achieving
      Cardiovascular Health in Canada) partnership advocates that health promotion for
      healthy lifestyles be incorporated into practice, and that the consistent
      messages and professional skills required to motivate patients and the public be
      acquired through interprofessional education and development. Professional
      education specialists are essential members of health care promotion teams with
      expertise to develop educational interventions that impact behaviours of health
      professionals and subsequent patient outcomes. Continuing medical education (CME)
      is in evolution to continuing professional development (CPD), and then to
      continuing inter-professional development (CID). Providers of health promotion,
      public health, and health care can work with health educators to complete the
      cascade of learning, change in practice, and improvement in patient outcomes. The
      Canadian health care system can empower Canadians to achieve cardiovascular
      health, the most important health challenge in the 21st century.

PMID- 11962122
TI  - From death and disability to patient empowerment: an interprofessional
      partnership to achieve cardiovascular health in Canada.
AB  - This paper proposes a paradigm shift in health care from a focus on death and
      disability to one on health empowerment resulting in improved cardiovascular
      lifestyles for all Canadians. It describes a national interprofessional
      initiative to achieve this new vision in the area of cardiovascular health
      promotion. Achieving Cardiovascular Health in Canada (ACHIC) is a partnership of
      health professional associations and other health advocate groups whose vision is
      to promote optimal cardiovascular health (including cerebrovascular health) for
      all Canadians through interprofessional partnership initiatives and support
      systems. ACHIC's objectives are to: 1) identify system barriers and supports to
      cardiovascular health; 2) develop strategies that will have a positive impact on
      the practices of health professionals/educators in the promotion of
      cardiovascular health; 3) develop an interprofessional national approach to
      support strategies to achieve cardiovascular health in Canada; and 4) support the
      development and delivery of consistent, evidence-based messages by health
      professionals/educators for promotion of cardiovascular health.

PMID- 11962123
TI  - [Improved pig health with farm management systems. Project 'Beautiful stream of
      pigs' 21].
AB  - As part of the project 'Clean pigs', an inventory was made of the different pig
      farm management systems described in the literature. These systems were evaluated
      for their potential use in improving animal health, focusing on the pathogens
      important in the Netherlands. The most promising systems for the control and/or
      eradication of pig pathogens in the Netherlands can be divided into two groups
      (with decreasing effect): I. Eradication from an existing positive population.
      The best systems for this are Embryo Transplantation (ET), Specific-Pathogen Free
      pigs (SPF), Piglet Snatching and Segregated Weaning (SW). II. Strategic
      veterinary and breeding strategies. The best systems for this are Freeze
      infection, test and removal, Test and removal, Vaccination, Medical elimination,
      Strategic medication and Genetic resistance. Farm systems can be a big help when
      trying to improve animal health, but the 'biosecurity' measures on the farm are
      at least of equal importance.

PMID- 11962124
TI  - [Transgenic cattle constitute a breakthrough in production of innovative
      medicine. From milk to medicine].
AB  - The continuously increasing demand for biomolecules, e.g. human proteins, for
      applications in human health care, is one of the main driving forces for the
      development of safe, large-scale production systems. One very promising approach
      is the production of biomolecules in the milk of transgenic cattle. By using
      nuclear transfer technology, transgenic cattle can be generated in a very safe
      and efficient manner, thereby offering a significant time reduction when compared
      to conventional breeding methods. As a result, that the transgenic cattle
      platform offers an efficient, safe and cost-effective method for producing large
      amounts of biopharmaceuticals, which is essential to the development of
      innovative health care products.

PMID- 11962125
TI  - [Interview with Henk Jan Ormel, candidate for the House. 'As a veterinarian you
      are also an architect...' (Interview by Sophie Deleu)].

PMID- 11962126
TI  - [Microbiological threat by food and animals].

PMID- 11962127
TI  - [Discussion of vaccination policy useful?].

PMID- 11962128
TI  - [Foot and mouth disease control].

PMID- 11962129
TI  - [Sandwich cloned monkey].

PMID- 11962130
TI  - [Wandering angel of death].

PMID- 11962131
TI  - [Starting at April 1 the Veterinary Quality Organization becomes independent.
      Certified out of the quality in the veterinary practice].

PMID- 11962132
TI  - Enough rope to hang yourself. Medicare improvements lessen chance for reforms.

PMID- 11962133
TI  - D.C.'s community health packs it in. Not-for-profit joint venture agrees to be
      acquired by Amerigroup.

PMID- 11962134
TI  - Not so peachy in Georgia. Climbing liability insurance premiums threaten to close
      more hospitals.

PMID- 11962135
TI  - The long road back. Calif. hospital beating off plague of fiscal ailments.

PMID- 11962136
TI  - Tossing and turning. Florida restless from debate over bed numbers.

PMID- 11962137
TI  - Not a team player. Maine cardiac center wants to limit docs to performing
      surgeries only at its facility.

PMID- 11962139
TI  - What California has started.... Staffing ratios, union activism are national
      solutions to the nurse shortage.

PMID- 11962138
TI  - Ad campaigns pay off. N.Y. healthcare tries lobbying public, not lawmakers.

PMID- 11962140
TI  - Rx for salvaging a career. Problem physicians get a second chance through
      controversial remedial education programs.

PMID- 11962141
TI  - Unexpected turn of events. After a five-year battle, an appeals court overturns
      the fraud convictions of two former Columbia/HCA executives.
AB  - For former Columbia/HCA executives Jay Jarrell and Robert Whiteside, the
      overturning of their 1999 fraud convictions was a get-out-of-jail-free card. A
      federal appeals court ruled that the government didn't prove its case against
      them and that the rules they were meant to follow were confusing. And if the
      government didn't prove its case here, what does this judgment mean for other
      fraud cases?

PMID- 11962142
TI  - Industry group laments side-stepping of HIPAA. Bureaucratic failure, flawed rules
      lead to delays in compliance, fiscal waste, coalition charges.

PMID- 11962143
TI  - Congress, Bush wrangle over cost of Medicare.

PMID- 11962144
TI  - Baxter cuts CEO's bonus after dialyzer-linked deaths.

PMID- 11962145
TI  - Inching up. Part II: peritoneal dialysis.

PMID- 11962146
TI  - The behavior contract as a positive patient experience.

PMID- 11962147
TI  - CAN the new K/DOQI guidelines make a difference for the CKD patient.

PMID- 11962148
TI  - Developing a CRI pre-screening program for African-Americans.

PMID- 11962149
TI  - The economics of dialyzer reuse in ESRD.

PMID- 11962150
TI  - Preventing malnutrition: management of the pre-ESRD patient.

PMID- 11962151
TI  - The impact of nutrition and fitness on quality of life.

PMID- 11962152
TI  - Vitamin D update. Medicare carrier abandons plan to "ration" i.v. vitamin D in
      North Carolina, but not South Carolina.

PMID- 11962153
TI  - Economics, focus on pre-dialysis may help stabilize peritoneal dialysis in
      Canada.
AB  - PD use has stabilized somewhat in Canada after five years of relative decline.
      Fiscal constraints on health care funding in general and fiscal incentives in
      some provinces to do PD may be contributing to this, and may lead to PD growth in
      the years ahead. Other factors that may help PD to grow are the proliferation of
      predialysis clinics with an associated emphasis on the patient's right to make an
      elective modality choice, new innovations in treatment, ongoing evidence of
      improving outcomes, and perhaps, more simplicity in prescribing the modality in
      the post-ADEMEX era.

PMID- 11962154
TI  - Polling renal professionals. Changing roles and responsibilities of nephrology
      social workers: are they appropriate?

PMID- 11962155
TI  - Faced with staffing minimums, hospitals lure nurses with sign-on bonuses.

PMID- 11962156
TI  - Post-conference features latest developments in care for patients with HIV/AIDS
      and HIV nephropathy.

PMID- 11962157
TI  - Processed meat consumption linked to type 2 diabetes.

PMID- 11962158
TI  - Engineered bladder may be used in transplant surgery.

PMID- 11962159
TI  - ESRD data system needs a fix. Lack of updates impacts beneficiaries, costs
      Medicare; USRDS looks elsewhere for accurate data.

PMID- 11962160
TI  - Patients develop immune reaction to Eprex.

PMID- 11962161
TI  - Recruitment & retention. Is distance learning an answer to the shortage of periop
      RNs?

PMID- 11962162
TI  - ORs consider how to comply with JCAHO staffing standard.

PMID- 11962163
TI  - Bronchoscope recall falls through cracks.

PMID- 11962164
TI  - What you should know about device recalls.

PMID- 11962165
TI  - Planning a technology roadmap for your OR.

PMID- 11962166
TI  - More positive staff boosts surgeon satisfaction.

PMID- 11962167
TI  - Anesthesia standards aim to improve safety.

PMID- 11962168
TI  - Diminishing returns for larger ASCs.

PMID- 11962169
TI  - The courage to care for ourselves.

PMID- 11962170
TI  - Dementia in the new millennium.
AB  - Alzheimer's disease, the leading form of dementia, is expected to increase
      exponentially in the next 50 years. An overview of types of dementia and the
      typical presentation of AD are described. In addition, rationale for early
      assessment and methods for diagnosing the disorder are detailed.

PMID- 11962171
TI  - Current concepts and pharmacologic treatment of heart failure.
AB  - Heart failure is one of the most common diagnoses and reason for hospitalization
      in the United States. Ace inhibitors, diuretics, beta-blockers and digitalis are
      the leading agents in pharmacologic management of heart failure. In order to
      improve patient outcomes, adult-health nurses need to understand the diagnosis,
      pathophysiology, nursing interventions, and pharmacologic treatment of this
      common disorder.

PMID- 11962172
TI  - Morbid obesity: a nursing care challenge.
AB  - Obesity is one of the nation's most serious health problems. When individuals are
      overweight, they are at risk for disease, medical complications, and death.
      Patients are considered morbidly obese or bariatric when their weight far exceeds
      recommended guidelines. Excess weight in these individuals increases morbidity
      and mortality, and causes numerous care challenges. Nurses caring for bariatric
      clients should recognize the need to use specialized assessment and management
      strategies to prevent poor patient outcomes.

PMID- 11962173
TI  - Genetics in transplantation.
AB  - Genetic therapies will play a major role in the future of transplantation. This
      review of basic genetic content helps describe how genetic mutations can lead to
      end-organ failure, and how several genetic therapies will be adapted in
      transplantation.

PMID- 11962174
TI  - Sexual unattractiveness: a patient's story.
AB  - Individuals experience a variety of responses to serious acute and chronic
      illness. This case study examines one patient's psychosocial responses to body
      image distortion from peritoneal dialysis and hemodialysis. It integrates
      research, theory, and practice, thus enhancing understanding of this response.
      Through the aforementioned interventions, nurses can assist patients to accept
      this psychosocial problem, seek further professional help, and thus improve their
      well-being.

PMID- 11962175
TI  - "Spare the cough, spoil the airway:" back to the basics in airway clearance.
AB  - Cough is the natural defense mechanism for protection of the respiratory tract.
      It is used to mobilize and remove secretions from the respiratory tree, moving
      them from the peripheral to the central airways. Effective airway clearance for
      individuals with cystic fibrosis is an essential component of daily therapy
      because of the thick and tenacious secretions that accumulate in their airways.
      Regardless of the airway clearance method used, effective coughing is the key
      part of the process. Understanding airway physiology and utilizing the equal
      pressure point and the collateral ventilation system between airways will make
      airway clearance activities most effective. Finding a match between an effective
      airway clearance method that uses cough effectively and a patient's preference is
      the challenge for the care provider.

PMID- 11962176
TI  - An interdisciplinary project that changed practice in feeding methods after
      pyloromyotomy.
AB  - Postoperative feeding methods for infants with hypertrophic pyloric stenosis
      (HPS) have remained unchanged for several decades. Conventional feeding methods
      include a prolonged NPO period immediately after pyloromyotomy, followed by a
      slow, incremental increase in volume and strength of feedings. Recently, some
      surgeons have ascribed to a more rapid or ad lib feeding advancement. Needing
      evidence before making changes to current practice, inpatient surgical nurses at
      Children's Hospital Boston collaborated with a general pediatric surgeon to
      conduct a 6-month retrospective study of 36 HPS patients comparing conventional
      regimen feeds to ad lib feeds by surgeon preference. The project resulted in a
      study published in the Journal of Pediatric Surgery and demonstrated for staff
      that the interval from the operating room to toleration of full feedings was less
      with the ad lib group as compared to the conventional regimen group. In addition,
      discharges occurred sooner without readmissions occurring in either group. The
      project resulted in a change in practice of feeding HPS patients postoperatively
      from the conventional regimen method to the ad lib method.

PMID- 11962177
TI  - Humor: a coping strategy for pediatric patients.
AB  - In the past 20 years, nurses have become concerned with children's response to
      stressors and their ability to cope with them. Humor is one strategy that
      pediatric nurses can use to help children cope with illness and hospitalizations.
      Although there is little scientific research, there is some theoretical and
      anecdotal support for the use of humor as a coping strategy. Understanding the
      developmental aspect of humor is essential for nurses and families, and McGhee's
      developmental stages of humor are linked to Piagetian stages of cognitive
      development. Additional discussion describes related diagnoses, assessment, and
      outcomes for humor interventions as well as considerations for determining the
      appropriate and inappropriate use of humor. Numerous activities to implement
      humor in pediatric clinical settings are presented. The need for further research
      to evaluate humor intervention as an effective coping strategy is recommended.

PMID- 11962178
TI  - Developing cultural competence in health care settings. National Center for
      Cultural Competence.
AB  - Increasing cultural and linguistic competence in health care settings is
      important for several reasons, including: responding to current and projected
      demographic changes in the United States; eliminating long-standing disparities
      in the health status of people of diverse racial, ethnic, and cultural
      backgrounds; improving quality of both services provided and health outcomes;
      meeting legislative, regulatory, and accreditation mandates; gaining a
      competitive edge in the market place; and decreasing the likelihood of
      liability/malpractice claims. Changes in policies, structures, practices, and
      procedures are often needed to bring about improvements in this arena. To support
      the process of change, The National Center for Cultural Competence (NCCC) was
      funded to increase the capacity of health care and mental health systems,
      institutions, programs, and providers to design, implement, and evaluate service
      delivery systems for cultural and linguistic competence. Several checklists
      developed by the NCCC are presented here for use by individual practitioners,
      programs, and institutions in assessing aspects of cultural competence.

PMID- 11962179
TI  - Practical approaches to clinical research. An update on growth charts, old and
      new.

PMID- 11962180
TI  - Mothers in the media: blamed and celebrated--an examination of drug abuse and
      multiple births.
AB  - The media has always had a profound interest in mothers and birth stories. This
      study examined the difference between media portrayal of "good" mothers and "bad"
      mothers. Did the media cover potential harm to fetuses and would-be children in
      the same way for two groups of mothers: (a) pregnant women addicted to illicit
      drugs and (b) women who chose to continue a high-order, multiple birth pregnancy?
      Two searches were conducted on Lexis-Nexis, one with keywords "McCaughey and
      birth" and another with the keywords "pregnancy and illegal drugs." A total of
      210 articles were coded for the McCaughey search, and 90 articles were coded for
      the pregnancy and illegal drugs search. The media did not address potential harm
      in the same way in both cases. The harm from illegal drugs was exaggerated, while
      the harm from multiple births was downplayed. Consequently, the media response
      towards the two cases was dramatically different. In conclusion, the communal and
      regulatory responses to both drug-addicted pregnant women and large multiple
      births caused by infertility treatments needs to be rethought.

PMID- 11962181
TI  - Pediatric management problems.

PMID- 11962184
TI  - Tracheostomy troubles.

PMID- 11962183
TI  - Strategies for overcoming barriers in implementing evidence-based practice.
AB  - In summary, there are a variety of strategies that can be used to overcome
      barriers to implementing EBP in nursing. However, these strategies must be
      formally evaluated to determine their effects on changing nurses' knowledge,
      beliefs, and attitudes about EBP as well as their effects on changes in practice.
      For evidence-based care to evolve more quickly in nursing, individuals and
      systems must make a commitment to advancing EBP and allocating resources for this
      purpose. Basic and graduate nursing programs must begin to teach the value and
      foundations of EBP if nursing is to create a culture where EBP is the "norm" and
      not the rarity. Since research has found that health care professionals find
      practice more rewarding when engaging in EBP (Dawes, 1996), this movement could
      help to facilitate the retention of nurses in a time when the nursing profession
      is facing severe shortages. Finally, since there are numerous areas in which
      evidence does not exist to support current nursing practices, researchers and
      APNs need to unite in order to design and conduct studies to answer high-priority
      compelling clinical questions.

PMID- 11962182
TI  - Children with asthma: initial development of the child resilience model.
AB  - PURPOSE: The purpose of this study was to develop a clinically relevant
      conceptual model of resilience in children based on theoretical relationships
      between family environment, specific child characteristics, and selected health
      outcomes. METHODS: A correlational study method was used to study a
      nonprobability, volunteer sample of 235 children, diagnosed with asthma on daily
      medication. FINDINGS: Findings revealed that the paths in the inner core of a
      resilience model were statistically significant. Fifteen percent of the variance
      in the illness indices outcome for children with asthma was explained by family
      environment, specific child characteristics, appraisal and coping, and child
      perceived quality of life. A child's sense of coherence and self-esteem, as
      mediated by a child's appraisal of asthma, accounted for 37% of the variance
      explained in the perceived quality of life. CONCLUSIONS: Nurses and physicians,
      committed to working in partnerships with parents, can help foster specific child
      characteristics that impact the effects of asthma.

PMID- 11962185
TI  - What do pediatric nurses do? Results of the role delineation study in Canada and
      the United States.
AB  - The National Certification Board of Pediatric Nurse Practitioners and Nurses
      (NCBPNP/N) is responsible for developing, maintaining, and administering the
      general pediatric nursing certification examination. A key feature is to ensure
      that the template used to construct the examination is formulated on the basis of
      current practice in pediatric nursing. Changes in health care require that a
      formal examination be conducted every 7-10 years to assess current practice and
      revise the test specifications as indicated. The purpose of this study was to
      identify the roles and responsibilities of the general pediatric nurse as a first
      step in continuing the job-related certification examination program. The purpose
      was to also analyze areas of knowledge, skill, and ability for pediatric nurses.

PMID- 11962186
TI  - Pediatric immunization update 2002.
AB  - The field of pediatric immunizations is growing and changing as new vaccines are
      becoming available and previous diseases are being eradicated. Due to the
      complexity and evolution of vaccine-preventable diseases, pediatric health care
      providers must routinely review the current childhood immunization
      recommendations. A review of immunology and the principles of vaccination provide
      background knowledge for information pertaining to disease transmission and the
      current recommended vaccine schedule. Vaccine administration guidelines and
      techniques are presented in table format. An overview of new vaccine research and
      development and a discussion of vaccine safety and immunization resources are
      also included.

PMID- 11962187
TI  - Catheter-related thrombosis in pediatrics.
AB  - Venous access devices (VADs) are being used in the pediatric setting with
      increasing frequency. To care for these devices, clinicians need to be cognizant
      of the complications that occur. The two most often encountered catheter-related
      complications are infection and thrombosis. This article begins with an overview
      of hemostasis as well as the pathway for fibrinolysis. Signs, symptoms, and
      treatment options available using thrombolytic agents in the three most common
      catheter-related thromboses are presented including: (a) fibrin sheath
      obstruction, (b) subclavian vein thrombosis, and (c) superior vena cava
      thrombosis. Since treatment options using thrombolytic therapy are becoming more
      widely used, clinicians are expected to be knowledgeable of these agents. A brief
      overview of the more common investigational agents used for the treatment of
      catheter-related thrombosis is also provided. VADs in children have played a
      significant role since being introduced more than 20 years ago. VADs often
      provide the only means available for the delivery of chemotherapeutic agents,
      blood products, nutritional support, fluids, antibiotics, and other medications
      as well as easier access to blood sampling. The convenience of these devices has
      not only decreased the pain and anxiety of frequent peripheral access for
      intravenous (i.v.) therapy and blood sampling, but has decreased frequent trips
      to the clinics or hospitals that are otherwise often required. In recent years
      family members are using VADs more frequently at home for the delivery of
      medications.

PMID- 11962188
TI  - New molecular targets of breast cancer therapy.
AB  - BACKGROUND: The development of new chemotherapeutic agents and concepts of
      radiation therapy, administered as primary, adjuvant and palliative therapy, has
      led to new perspectives in breast cancer therapy. Apart from conventional
      chemotherapy, recently developed novel agents interfere with molecular mechanisms
      that are altered in cancer cells. Those targets are not necessarily breast cancer
      specific. In this review we will focus on novel agents with potential or already
      proved benefit to breast cancer patients. Promising strategies include inhibition
      of growth factor receptors, blocking of tumor angiogenesis and signal
      transduction pathways, modulation of apoptosis, cancer vaccination, and
      inhibition of invasion and metastasis. METHODS: Reports of relevant studies
      obtained from a search of MEDLINE and studies referenced in those reports were
      reviewed. RESULTS: Apart from trastuzumab, other further developed compounds show
      promising results in clinical studies as a second generation of growth factor
      inhibitors. Different approaches in anti-angiogenetic therapy are under
      preclinical and clinical phase-II trials. Pro-apoptotic agents show synergistic
      effects with docetaxel in a clinical phase-I trial. Other compounds that target
      HSP 90, histone deacetylase and HMG-CoA reductase target atypical apoptotic
      pathways being lethal to tumor cells only but not to normal tissue, suggesting a
      tumor-specific way of action. MMP inhibitors have been demonstrating promising
      results in patients with refractory malignant pleural effusion in a phase-I
      trial. Several tyrosine kinase inhibitors currently under clinical investigation
      preliminarily show hopeful results in patients with advanced breast cancer.
      Furthermore, recent progress in defining the immunogenic epitopes of tumor
      antigens has rejuvenated the interest in cancer vaccines. CONCLUSION: Typical
      dose escalation studies leading to the highest clinically still tolerated dose do
      not appear to be equally appropriate for the estimation of efficiency of those
      compounds as for conventional cytotoxic regimes. Rather, escalation up to an
      amount of therapeutic agent that is sufficient for maximum target inhibition
      should be promoted, where classical measures of cytoreduction such as complete or
      partial remission are replaced both by time to progression and treatment failure
      as an appropriate measure of the efficacy of an agent.

PMID- 11962189
TI  - Computed tomogram prior to prostatectomy. Advantage in defining planning target
      volumes for postoperative adjuvant radiotherapy in patients with stage C prostate
      cancer?
AB  - PURPOSE: To evaluate the influence of a preoperative computed tomogram (CT) on
      delineation of the planning target volume (PTV) for adjuvant radiation therapy of
      pT3 pN0 prostate cancer. PATIENTS AND METHODS: PTVs of ten patients who had an
      additional preoperative CT examination were contoured by three independent
      radiation oncologists. PTV included the former prostatic bed and seminal vesicles
      with a safety margin. First PTVs were drawn without knowledge of the preoperative
      CTs and in a second attempt, this procedure was repeated with these CTs available
      for visual comparison. Changes in PTV dimensions for every patient were analyzed.
      RESULTS: In 93% of all PTVs there was a decision to increase the PTV after
      viewing the preoperative CT images. Mean PTV length increased from 7.3 to 8.4 cm
      and PTV volumes expanded 26% from 244 to 308 cm3. These differences were
      statistically significant for all three participating radiation oncologists.
      CONCLUSION: Planning target volume definition probably is a critical factor in
      adjuvant radiation therapy after radical prostatectomy. As there is a
      considerable incertainty in PTV definition a preoperative CT is helpful and
      therefore may have beneficial influence on results.

PMID- 11962190
TI  - [Virtual bolus for inversion radiotherapy planning in intensity-modulated
      radiotherapy of breast carcinoma within the scope of adjuvant therapy].
AB  - BACKGROUND: Intensity modulated radiotherapy (IMRT) provides better sparing of
      normal tissue. We investigated the feasibility of inverse treatment planning for
      IMRT in adjuvant radiotherapy for breast cancer. MATERIAL AND METHODS: In
      addition to radiotherapy planning in conventional technique with tangential
      wedged 6-MV-photon beams we performed inversely planned IMRT (KonRad). In the CT
      scans for treatment planning we defined a 10-mm bolus of -60 HE density. The
      influence of this bolus on planning optimization was determined by optimization
      without and dose calculation with and without bolus. Dose calculation after dose
      optimization with bolus was performed using different bolus thickness to
      determine the influence of the bolus on dose calculation. The results were
      compared with dose distribution in conventional technique. RESULTS: Inverse
      optimization with a dose algorithm which considers tissue inhomogeneity results
      in unintended dose increase at the patient surface. With a virtual 10-mm bolus
      used for inverse optimization the dose increase was reduced. Thus, skin sparing
      was identical to conventional planning. The relative dose distribution was
      negligibly affected by the use of a 10-mm bolus. Difference in absolute dose was
      3.4% compared to calculation without bolus. Therefore, the bolus must be removed
      before final dose calculation. CONCLUSION: The realization of inverse
      optimization for IMRT of the breast requires the use of a virtual bolus. Thereby,
      IMRT in accordance to the consensus recommendations of the EORTC, BCCG and EUSOMA
      is possible. Especially, the same target definition as in conventional technique
      may be used. IMRT techniques with a conventional beam arrangement of two
      tangential fields or multiple beam techniques can be realized.

PMID- 11962191
TI  - [Experimental data for administration of insulin-like growth factor 1 (IGF-1) and
      basic fibroblast growth factor (bFGF) for prevention of radiation myelopathy].
AB  - BACKGROUND: Current models of radiation myelopathy provide a rationale for growth
      factor-based prevention strategies. Thus, we tested whether insulin-like growth
      factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) alone or in
      combination modulate radiation tolerance of the rat cervical spinal cord.
      MATERIALS AND METHODS: The cervical spinal cord of 68 adult Fisher F344 rats
      received a total dose of 30-36 Gy, given as a single fraction of 16 Gy followed
      by a second radiation dose of 14-20 Gy. Continuous intrathecal infusion of bFGF
      (44 rats) or saline (24 rats) into the cisterna magna was given concomitantly. A
      further experiment included 14 additional rats which were treated with
      subcutaneous injection of IGF-1 parallel to irradiation with a total dose of 34
      Gy or 36 Gy. 20 rats received combined treatment, i.e. intrathecal infusion of
      bFGF plus subcutaneous injection of IGF-1, starting 24 hours before irradiation
      (total dose 33 Gy or 36 Gy) for a total of 4 days. Animals were followed until
      myelopathy developed or for a maximum of 12 months. Histopathologic examinations
      were performed post mortem. RESULTS: Treatment with bFGF alone or IGF-1 alone
      increased the median time to myelopathy significantly. In the 36-Gy group, after
      combination treatment a comparable prolongation of latency was seen. Moreover,
      rats treated with 33 Gy and combined bFGF plus IGF-1 showed a significantly
      reduced risk of myelopathy, too (p = 0.0015, Figures 1 and 2). CONCLUSION:
      Combination of IGF-1 and bFGF was more potent than single agent treatment. We
      observed a significantly reduced myelopathy rate at an intermediate radiation
      dose level and a longer time to myelopathy at a high-dose level. This finding
      strengthens the evidence that brief therapeutic intervention can decrease
      radiation-induced neurotoxicity. Further studies will be undertaken to optimize
      this strategy.

PMID- 11962192
TI  - Measurement of quality of life in head and neck cancer patients utilizing the
      quality of life radiation therapy questionnaire.
AB  - BACKGROUND: Quality of life (QOL) measures give patients the possibility to
      express subjective changes in wellbeing. We aimed to translate the radiation
      specific quality of life questionnaire (QOL-RTI) and the companion head and neck
      module (H&N) questionnaire into German and to test its reliability, validity and
      sensitivity. PATIENTS AND METHODS: After translation and final revisions based on
      qualitative interviews with ten patients, 97 head and neck cancer patients were
      screened for eligibility. Patients answered the 38 items questionnaire at
      baseline and twice in week 4 of radiotherapy for test-retest reliability.
      Internal consistency was calculated using Chronbach's alpha. Patients also
      completed the functional assessment of cancer tool plus head and neck (FACT-G
      plus H&N) for concurrent validity. Item analyses were performed to test the
      sensitivity. RESULTS: Chronbach's alpha yielded alpha = 0.85 for the QOL-RTI and
      alpha = 0.80 for the H&N module, test-retest reliability scores were r = 0.87 and
      r = 0.83, respectively. The correlation of the QOL-RTI plus H&N and the FACT plus
      H&N was r = 0.79. Questionnaire sensitivity was supported by significant changes
      in the mean score of 45.8% of the QOL-RTI items and 78.6% of the H&N items
      between baseline and week 4 of radiotherapy. CONCLUSIONS: The German version of
      the QOL-RTI was shown to be a reliable, valid and sensitive tool to assess the
      quality of life of patients undergoing radiotherapy. The H&N module is useful for
      patients undergoing treatment for head and neck cancer.

PMID- 11962193
TI  - Vitiligo at the sites of irradiation in a patient with Hodgkin's disease.
AB  - BACKGROUND: Vitiligo is one of the most common skin disorders. However, the
      etiology of vitiligo is still unknown. Current hypotheses discuss autoimmune,
      autotoxic and neuronal mechanisms. Here we report the case of radiation-induced
      depigmentation of the skin of a patient with Hodgkin's disease and 25-year
      history of vitiligo. PATIENT AND METHOD: We compared possible differences in skin
      color, skin moisture, microcirculation and skin elasticity between normal skin
      and skin exhibiting persistent depigmentation in a 37-year-old patient 40 months
      after completion of external beam radiotherapy. RESULTS: Colormetrically we found
      a dose-dependent decrease of the red/green and yellow/blue saturation combined
      with an overall increase in brightness in depigmented skin when compared with
      normal skin. This was in agreement with a loss of melanocytes in vitiligo.
      Depigmentation was complete in areas receiving 40 Gy. Areas which received 30 Gy
      showed depigmentation only if the skin dose was increased by the loss of depth of
      the build-up dose region in areas with direct contact with the irradiation table.
      We could not show any change in skin moisture, microcirculation or skin
      elasticity. CONCLUSIONS: Complete radiation-induced depigmentation of skin from
      patients suffering from vitiligo is a side effect of radiation therapy. Patients
      should be informed about this side effect by the radiooncologist. Preventing the
      loss of depth of the build-up dose region might improve the cosmetic results of
      radiation therapy in patients with history of vitiligo.

PMID- 11962195
TI  - [Value of postoperative radiochemotherapy with 5-fluorouracil plus leucovorin in
      stage IB-IV M0 stomach carcinoma].

PMID- 11962194
TI  - [Initial results of randomized studies of metastatic colorectal carcinoma urge
      careful and controlled use of CPT-11].

PMID- 11962196
TI  - [Secondary neoplasms in 5-year survivors of cancer in childhood: results of the
      Childhood Cancer Survivor Study].

PMID- 11962197
TI  - [Some aspects of the resistance of natural foci of zoonosis infections with an
      example of the tick-borne encephalitis].
AB  - Epidermiological material reflecting some spatio-temporal aspects of the natural
      foci of tick-born encephalitis resistance has been analysed. The investigation
      carried out can used as a base for elaboration and realisation of factor
      prognoses concerning natural foci of zoonosis infection.

PMID- 11962198
TI  - [Estimation of the absolute density of adult Ixodes persulcatus ticks according
      to the results of collecting per flag-hour (Ixodidae)].
AB  - The results of two methods of estimation of abundance of adult Ixodes persulcatus
      ticks, the absolute (at the sample plots) and the relative (per flag-hour)
      estimations, were compared. Collecting of ticks and estimation of their abundance
      was conducted during 9 years at the forests of the Far East and Pre-Ural region.
      The total of 1995 plots (100 sq. m each) were studied and 865 flag-hours were
      carried out. A good correlation of the data, obtained by these methods, was
      revealed. The average number of adult ticks, collected per flag-hour,
      approximately corresponds to the average number of ticks, activated during the
      season at 100 sq. m. The possibility of corresponding re-calculation of the
      results of estimation per flag-hour into the parameters of tick population
      density was evaluated. It was shown that such re-calculation gives good results.
      Their inexactitude usually doesn't exceed the statistical error of the
      parameters, obtained by the estimation of tick density at sample plots.

PMID- 11962199
TI  - [Combined manifestations of natural foci in the territory of the Vologda
      province].
AB  - Based on epizootological and epidemiological investigations in the Vologda
      province since 1958 till 2000, the combined territorial and temporal
      manifestations of natural foci of diseases was revealed. A natural focus occupies
      a complex of biotopes, and in different time the focus is activated in different
      areas, such as a river plain, marsh, meadow-field, and forest. Most commonly an
      activation of the natural focus appears in a border zone of three biotopes,
      namely, a forest, meadow-field, and river plain. A dependence of activation of
      various natural foci upon local climate conditions and fluctuations of
      micromammalian host number are considered.

PMID- 11962200
TI  - [Parasite communities and a fish spawn].
AB  - High values of dominance index, low values of evenness and Shannon index are
      characteristic of component parasite communities of prespawning (Prosopium
      cylindraceum) and spawn migratory fishes (Coregonus autumnalis, Oncorhynchus
      nerka). Autogenic specialists are dominant in the component parasite communities
      of C. autumnalis. The component parasite communities of P. cylindraceum and O.
      nerka are dominant in a content of generalist species. The O. nerka parasite
      communities are communities "sentenced to death". Low values of dominance index,
      high values of evenness abd Shannon index are peculiar to component parasite
      communities of prespawning and spawning cyprinid fishes (Phoxinus phoxinus,
      Oreoleuciscus humilis). Autogenic specialists are dominant. Increase of dominance
      index and decrease of two other indexes characterize the postspawning period. The
      same tendency characterises infracommunities. Thus, the component parasite
      communities respond differently to the fish spawn of the cyprinid and
      coregonid/salmonid fishes. Similarity is in the dominance of autogenic
      specialists in one case only (C. autumnalis). These differences are defined by
      the mode of fish stock formation for spawn. The cyprinids congregate for spawning
      and move apart for foraging and vice versa is observed in the coregonids and
      salmonids. Autogenic specialists dominance seems to be the important adaptation
      to reduce a negative effect to host during spawning. Bush and Kennedy in 1994
      established that "parasites live in patches (host individuals) and fragments
      (host populations)". They consider the host fragmentation as "hedging your bets
      against extinction" due to frequency and magnitude anthropogenic factors, which
      increase fragmenting of host populations. This conclusion was made for a species
      level. From the other hand the fragmentation is a natural feature for a single
      host population too. Such fragmentation is a host population structure. The role
      of fragmentation is obvious from the data on component parasite communities
      during fish spawn. The fragmentation decreases in the cyprinids and increases in
      the salmonids that leads to the growing of the cyprinid component parasite
      communities diversity and to declining the salmonid component parasite
      communities diversity. Nevertheless the role of host population structure in a
      component parsite community structure is not obvious, because parasites are able
      or not able to "recognise" different host subpopulation groups. It is well known
      from data on parasite species population biology. Such recognizable subpopulation
      groups or groups can be a "real fragment" for the parasite community. The
      question is what parameters could be used for this purpose on a component
      community level. Host population age structure can be used as an example, because
      the age groups are one of the invariable population characters. Value of Shannon
      index for component parasite communities of spawn migratory O. nerka (5+) is
      similar to that of fishes of 1+ age. Difference is statistically insignificant.
      It is insignificant between the parasite communities of 2+ and 3+ age groups too.
      Fishes of these two groups could be defined as a real united fragment. It spite
      of similarity between the fishes of 5+ age group and fish of 1+ age group they
      are not united fragment. The parasite community of 1+ age fishes is not
      stabilized yet and one of 5+ age is a community "sentenced to death". Thus the
      structuring of O. nerka freshwater parasite communities are defined by 3 real
      host age fragments: 1+ age group, 2 and 3+ age group, 4+ age group. It looks as
      that Shannon index is suitable parameter to study a parasite communities
      structure.

PMID- 11962201
TI  - [On ranges of the malaria mosquitoes (Diptera: Culicidae: Anopheles) of the
      Maculipennis complex on the territory of Russia].
AB  - Maps and distribution data are provided for the seven mosquito species of the
      genus Anopheles, the maculipennis group: Anopheles atroparvus, A. beklemishevi,
      A. maculipennis, A. messeae, A. malanoon, A. sacharovi and A. subalpinus.

PMID- 11962202
TI  - [Morphological peculiarities of schistosomatid cercariae of Trichobilharzia cf.
      ocellata group occuring in Moscow and Saint-Petersburg populations].
AB  - Morphology of schistosomatid cercariae of the genus Trichobilharzia (ocellata
      group) is described based on original and reference data. The material
      (Trichobilharzia cercariae) was collected in 1999-2000 from naturally 'infected
      snails Lymnaea stagnalis from Moscow and Saint-Petersburg megalopolises. The more
      accurate flame cell formula for these cercariae, as well as some aspects of
      chaetotaxy and eye morphology are given. The differences between cercariae from
      these regions were found. Based on a comparison of nef data with the reference
      data, it was found that the cercariae examined differ from those from the Central
      Europe.

PMID- 11962203
TI  - [Comparative morphological and gene systematics analysis of the Proteocephalus
      thymalli (Cestoda: Proteocephalidae), a parasite of graylings in lakes Hovsogol
      and Baikal].
AB  - Results of comparative morphological and gene analyses of the cestode
      Proteocephalus thymalli, an intestine parasite of the lakes Hovsogol (Thymallus
      arcticus nigrescens) and Lake Baikal graylings (Thymallus arcticus baicalensis)
      are presented for the first time. The results indicate that representatives of
      the P. thymalli from these fishes are really two different species.

PMID- 11962204
TI  - [Ultrastructure of genital system ducts of Diphyllobothrium latum
      (Cestoda:Pseudophyllidae): the ducts of the female reproductive system].
AB  - The components of the female reproductive system of Diphyllobothrium latum,
      including ovary, ovicapt, oviduct, vitelline ducts, vitelline reservoir, vagina,
      seminal receptacle, ootype with unicellular Mehlis's gland, ootype-uterine duct
      and uterus were observed with the electron microscope. The epithelium of the
      female reproductive system ducts consists of a nucleate syncytial layer.
      Structural differences in apical surface of the ducts, the number of nuclei and
      organoids in syncytial layer as well as the number of underlaid muscles were
      revealed. The regional differentiations of the uterus wall were registered. The
      middle and distal region of uterus was covered with microtriches. The filamentous
      microtriches were observed in apical surface of vagina. The epithelium of seminal
      receptacle and distal region of uterus were underlaided by the powerful muscle
      layers. The fertilization canal was revealed. It was shown that the formation of
      egg shells implemented by the deposit of vitelline globules in their surface in
      the ootype-uterine duct. Structural and functional differences of different parts
      of female apparatus in various groups of cestodes are conditioned by species
      biology.

PMID- 11962205
TI  - [Antimutagenic properties of bacteria: a review].
AB  - Lactic acid and propionic acid bacteria, bifidobacteria, and fecal enterococci
      associated with the activity of humans and animals caused antimutagenic effects
      (AME) on many test systems designed for detecting point mutations and chromosomal
      aberrations. Bacterial cells and some of their metabolites attenuate the
      mutagenic action of several genotoxic agents, and this effect is mediated by the
      mechanism of dysmutagenesis and/or bioantimutagenesis. Possible mechanisms of
      various AMEs and possible practical applications of antimutagenic properties of
      bacteria are discussed.

PMID- 11962206
TI  - [Optimization of conditions of preparative chromatography of carminomycin on a
      carboxylic cation exchanger].
AB  - Time course of equilibrium and nonequilibrium sorption of carminomycin on
      carboxylic cation exchanger BDM-12 has been studied. Physicochemical requirements
      and limits of mobile phase flow rate are determined for the regular mode of
      preparative chromatography under the conditions of sharpening of the
      chromatographic zone.

PMID- 11962208
TI  - [Bacterial succession on n-alkanes under the conditions of sulfate reduction].
AB  - The dynamics of species composition of a hydrocarbon-oxidizing bacteriocenosis of
      a ground suspension of Mozhaisk Reservoir has been studied. The bacteriocenosis
      was undergoing development in a paraffin film (model association composed of
      sulfate-reducing bacteria and hydrocarbon-oxidizing bacteria). The type of
      bacterial succession did not depend on the depth, from which ground samples were
      collected. Two microbial species (Pseudomonas sp. and Arthrobacter globiformis)
      were absolutely dominant. Pseudomonas sp. was dominant at the early and
      intermediate stages of the succession, whereas A. globiformis was present in the
      hydrocarbon-oxidizing bacteriocenosis throughout the whole period of the
      succession. There was a trend toward a gradual increase in the ratio of A.
      globiformis, and, by the end of the experiment, Pseudomonas sp. was replaced by
      A. globiformis almost completely. The bacterial species Micrococcus sp. and
      Rhodococcus erythropolis were minor components of the hydrocarbon-oxidizing
      bacteriocenosis under the conditions of sulfate reduction. The succession of
      species of hydrocarbon-oxidizing bacteria in the paraffin film of the model
      association reflects both the life strategy of the bacterial species under study
      and the degree of their tolerance to products of sulfate reduction.

PMID- 11962207
TI  - [Depolymerization of high-molecular-weight chitosan by the enzyme preparation
      Celloviridine G20x].
AB  - A low-molecular-weight water-soluble chitosan was obtained from high-molecular
      weight crab chitosan using the enzyme preparation Celloviridine G20x. Optimum
      conditions for the enzymatic hydrolysis were designed. The reaction should be
      performed for 4 h in a sodium-acetate buffer (pH 5.2) at 55 degrees C and the
      enzyme to substrate ratio of 1:400. Fractional extraction of chitosan hydrolysate
      by aqueous ethanol (ethanol: distilled water) yielded fractions with molecular
      weights in the range 3.2-26.4 kDa.

PMID- 11962209
TI  - [Entomopathogenic bacteria Bacillus thuringiensis as producers of restriction
      endonucleases].
AB  - A total of 115 collection strains of Bacillus thuringiensis, belonging to various
      subspecies, have been studied for the presence of DNA restriction-modification
      systems. Restriction endonucleases of 13 strains have been isolated and
      characterized. No considerable correlations between the taxonomic positions of
      the bacteria and the specificities of the endonucleases isolated have been
      detected. It is concluded that the enzymes with identical specificities are
      present in both the crystalliferous and acrystalliferous strains of the same
      subspecies.

PMID- 11962210
TI  - [Anaerobic degradation of biphenyl by the facultative anaerobic strain
      Citrobacter freundi BS2211].
AB  - Using a synthetic medium supplemented with biphenyl (a polycyclic aromatic
      hydrocarbon), a new bacterial strain of Citrobacter freundii was isolated from
      enrichment cultures containing soil and industrial wastewater samples of the
      Serpukhov Condenser Factory. This strain was found to be capable of degrading
      biphenyl under anaerobic conditions in the course of nitrate reduction. When the
      initial concentration of biphenyl in culture medium equaled 150 mg/l, the culture
      with a titer of 10(9) cells/ml degraded up to 26-28% of biphenyl in 3 days (28
      degrees C). At 250 mg/l, the culture with a titer of 10(7) cells/ml degraded 15%
      of biphenyl in 21 days. Approximately 10% of the substrate consumed was utilized
      completely, whereas the remainder underwent transformation.

PMID- 11962211
TI  - [Changes in lipid composition and carbohydrate composition of Aspergillus niger
      conidia during germination].
AB  - Data on the lipid composition and carbohydrate composition of Aspergillus niger
      conidia make it possible to characterize the individual germination stages and
      differentiate between the conidia capable of germination and those that lost the
      germination capacity. The following criteria are proposed: the ratio of
      phosphatidylcholine and phosphatidylethanolamine, the ratio of mannitol and
      arabitol, and the levels of sterols and free fatty acids. The role of these
      compounds in the biochemical background of cell transition from dormancy to
      active metabolism and their use as indices of the quality of inocula in
      biotechnological processes are discussed.

PMID- 11962212
TI  - [Amylases of the fungus Aspergillus flavipes associated with Fucus evanescens].
AB  - A promising producer of extracellular amylases, Aspergillus flavipes, was
      selected from 245 strains of marine fungi. Depending on the conditions of growth,
      this strain produced diverse amylolytic complexes. When grown on medium
      containing peptone and yeast extract (pH 7.0), A. flavipes synthesized three
      forms of amylase, differing in pH optimum (5.5, 6.0, and 7.5). A single form of
      the enzyme was synthesized either in the absence of peptone from the medium or at
      the initial pH value of the medium, equal to 8.6. The activity of the isolated
      amylase forms decreased in the presence of proteolytic enzymes. New, highly
      stable forms of amylase (with pH optima of 5.5 and 7.5 and maximum activity at 60
      80 degrees C) were synthesized in the presence of diisopropyl fluorophosphate, an
      inhibitor of proteases.

PMID- 11962213
TI  - [Protein and peptide factors from Bacillus sp.739 inhibit the growth of
      phytopathogenic fungi].
AB  - Thermolabile peptides inhibiting the growth of Helminthosporium sativum, a
      facultative phytopathogen, have been isolated from the low-molecular-weight
      fraction of extracellular metabolites of the strain Bacillus sp. 739. Paper
      chromatography of the fraction, followed by bioautography, revealed the presence
      of three components exhibiting antifungal activity. These components were
      separated by gel chromatography on Toyopearl HW-40. SDS-PAGE (the Laemmli
      procedure) demonstrated that only one component was a protein (MW, approximately
      14 kDa). The other two substances were polypeptides with molecular weights less
      than 6 kDa each. The protein factor inhibited the growth of H. sativum with a
      minimum effective concentration of 0.1 to 0.2 mg/ml.

PMID- 11962214
TI  - Antimicrobial activity of the resins obtained from the roots and stems of Cedrus
      libani and Abies cilicica.
AB  - The antimicrobial activity of the ethanol extract of resins obtained from the
      roots and stems of Cedrus libani and Abies cilicica was investigated using a disc
      diffusion method. Results revealed that crude extracts of the resins of both
      plants are highly effective against tested microorganisms by preventing their
      growth to a greater extent.

PMID- 11962215
TI  - [Antioxidant activity in fungi degrading lignocellulose substrates].
AB  - Considerable differences in lignin degradation by fungi of two ecological groups
      have been revealed. Xylotrophs cause a twofold decrease in the molecular weight
      of lignin. The degrading activity of saprotrophs is insignificant. Xylotrophs
      demethoxylate and oxidize lignin more rapidly than saprotrophs, showing a higher
      level of antioxidant activity. As follows from the comparison of the degrading
      and antioxidative effects, measurement of the antioxidant activity can be used in
      screening of fungi for the ability to degrade lignocellulose substrates.

PMID- 11962216
TI  - [Stabilization of diluted aqueous solutions of horseradish peroxidase].
AB  - Effects of pH, enzyme concentration, and various supplements on the catalytic
      activity, temperature stability, and secondary structure of horseradish
      peroxidase (HRP) were studied in diluted aqueous solutions. In 5.0 mM citrate
      phosphate buffer (pH 4.2) at 55 degrees C and infinite dilution, HRP was
      inactivated with a rate constant of 2.86 x 10(-3) s-1. CaCl2, BSA, and glycerol
      caused protective effects, whereas KCl, LiCl, maltose, PEG-6000 (at a
      concentration above 3%), Triton X-100, ethanol, and Kathon CG had an opposite
      effect and altered the secondary structure of HRP. Two HRP-stabilizing media: the
      "glycerol-based" one containing 10% ethanol and 20% glycerol, or the "protein
      based" one containing 0.1% Kathon CG and 0.2 g/l of BSA in 50.0 mM Tris-HCl
      buffer (pH 7.2) supplemented with 50 mM CaCl2 were developed, and the stability
      of HRP (0.36 nM) and its immunoglobulin, cortisol, and progesterone conjugates
      were compared in these two media. The protein-based medium displayed a greater
      stabilizing effect particularly on HRP-steroid conjugates.

PMID- 11962217
TI  - [Proteins and saponins in the lipid preparation obtained by extraction of soybean
      flour].
AB  - A complex lipid preparation was obtained by extraction of soybean flour with
      organic solvents. This preparation was shown to include not only phospholipids
      (major components), but also up to 30% saponins. These compounds were identified
      by TLC, HPLC, and 1H-NMR spectroscopy. Minor components of the lipid extract were
      represented by polypeptides associated with phospholipids via electrostatic or
      hydrophobic forces.

PMID- 11962218
TI  - [Effect of bacterial infection on the lipid composition of carp blood
      lymphocytes].
AB  - The initial stage of bacterial infection is characterized by an increase in the
      level of total lipids and polyenoic fatty acids in membrane phospholipids of
      blood lymphocytes of carp (Cyprinus carpio L.). In the fish infected with
      aeromonads, changes in the ratios of fatty acids in phospholipids are similar for
      either lymphocytes, liver, or whole blood. The extent to which these changes are
      pronounced depends on the original physiological status of the fish.

PMID- 11962219
TI  - [Group-specific antibodies against zearalenone and its metabolites and synthetic
      analogs].
AB  - Formation kinetics, specificity, and analytical potential of polyclonal
      antibodies raised in rabbits against BSA conjugates of carboxymethyloxime
      zearalanone (CMO-ZAN) and carboxymethyloxime-zearalenone (CMO-ZEN). Preparation
      of the conjugates involved conversion of CMO-ZAN and CMO-ZEN into activated
      esters and carbodiimide condensation. Two versions of a group-specific enzyme
      immunoassay (for zearalenone/alpha-zearalenone and zearalanol/alpha-zearalanol)
      based on heterologous combination of solid-phase antigens are described
      (sensitivity, 0.01 ng/ml).

PMID- 11962220
TI  - [Effect of ambiol on stem growth in regenerants of source and transgenic potato
      plants].
AB  - The effects of ambiol, a new growth regulator, on stem growth and morphological
      features of stem development have been compared in regenerants of potato (Solanum
      tuberosum L., var. Desire) plants transgenic for a defensin gene and in original
      potato plants. The original and transgenic plants exhibited differences in shoot
      development, which were observed both in control settings (no ambiol) and in the
      presence of various ambiol concentrations. In addition to normal plants of both
      forms, plant regenerants with morphological deviations were present in ambiol
      treated groups. It is suggested that the abnormal shoot development observed in
      original and transgenic potato plants treated with ambiol is associated with (a)
      hormonal changes caused by expression of the defensin gene in the transgenic
      plants and (b) effects of ambiol on the hormonal balance of the plants.

PMID- 11962221
TI  - [Changes in macromolecular characteristics and biological activity of hydrolytic
      lignin hydrolysate in the course of composting].
AB  - Composting of hydrolytic lignin by a microbial association changed its molecular
      weight composition, acid-based properties, and supramolecular structure.
      Specifically, by the end of the third month of composting, an increase was
      observed in its exchange capacity and the amount of negative charges, as well as
      in the content of phenyl, hydroxyl, and carboxyl groups. The use of this compost
      as a fertilizer for barley growth demonstrated that the changes increased the
      biological activity of hydrolytic lignin.

PMID- 11962222
TI  - [Content of alginic acid and fucoidan in fucus algae of the Barents sea].
AB  - Seasonal changes in the content of alginic acid and fucoidan have been studied in
      four species of fucus algae from the Barents sea: Fucus vesiculosus, F.
      distichus, F. serratus, and Ascophyllum nodosum. These polysaccharides are
      accumulated in the biomass of the algae during summer and autumn. To ensure
      complete processing of fucus algae it is recommended that the raw material be
      harvested within this period.

PMID- 11962223
TI  - [Characteristics and utilities of luminescent bacteria from the Black sea].
AB  - Luminescent bacteria, isolated from summer specimens of water of the Black sea,
      have been identified as strains of Photobacterium phosphoreum and Vibrio fischeri
      (two of each). Morphological, physiological, and biochemical properties of the
      four strains have been characterized, and the kinetic behavior of luciferases
      isolated therefrom has been studied. The sensitivity of the luminescence of the
      strains to certain toxic agents has been compared to that of the test strain Ph.
      phosphoreum (Cohn) Ford. The results obtained indicate that the new strains show
      promise as bioindicators.

PMID- 11962225
TI  - Knowledge and perceptions about back education among elementary school students,
      teachers, and parents in Belgium.
AB  - A back education program for Belgian elementary school children was evaluated
      using self-reported questionnaires before intervention and at three follow-up
      points during one year. Most children found the program interesting, important,
      and amusing. Intervention children (n = 347) showed better back care knowledge
      than control children (n = 359), and knowledge gained was retained over a period
      of one year. Back education did not result in increased fear-avoidance beliefs
      about physical activity, and intervention children reported more checking of
      their book bag weight than controls at all test moments. Self-reported behavior
      in relation to posture-related and back care related self-efficacy were affected
      only minimally by the program, possibly due to poor self-judgment. Involvement,
      fear-avoidance beliefs, and back care knowledge of teachers and parents of the
      intervention children showed low correlation with the children's perceptions and
      knowledge. Sufficient promise exists to justify further development and
      evaluation of early back education.

PMID- 11962224
TI  - [Milk ultrafiltrate as a promising source of angiogenin].
AB  - The use of membrane technologies in the production of soft cheese (children's
      food) is associated with the appearance of up to 80% of angiogenin in the
      ultrafiltrate. An electrophoretically homogeneous preparation of angiogenin (MW
      approximately 17 kDa) was obtained from milk ultrafiltrate by two-stage ion
      exchange chromatography. The yield of the angiogenin was approximately 60%, which
      corresponds to a 586-fold purification of the raw material. The obtained
      preparation retained stability in the course of lyophilization and could be
      stored at 4 degrees C for a long time without decomposition.

PMID- 11962226
TI  - Development of the Student Attitudes Toward School Safety Measures (SATSSM)
      instrument.
AB  - The Student Attitudes Toward School Safety Measures (SATSSM) instrument was
      developed as a new tool to assess high school students' attitudes towards school
      safety promotion methods. A theory-based pool of statements was scaled using
      Thurstone's equal appearing interval method by 186 student judges to yield a 30
      item instrument. The draft version was operationalized into a 5-point, Likert
      scale format, using a new sample of 182 students. Exploratory factor analysis
      suggested three factors: mediation, surveillance, and searching methods. The
      SATSSM was reduced to six items for each scale with a five-item social
      desirability scale added, and piloted with 66 new students. Final administration
      of the SATSSM to 166 new students yielded scale and overall internal
      consistencies exceeding .80 with low interscale correlations. A simultaneously
      administered questionnaire measuring perceptions of school safety suggested
      students possessed increased awareness of school violence, but they believed
      improving school safety is beyond their school's control.

PMID- 11962227
TI  - Influence of school, class, ethnicity, and gender on agreement of fourth graders
      to participate in a nutrition study.
AB  - This article describes the methods used to recruit fourth-grade children for a
      school-based study concerning the accuracy of their school breakfast and lunch
      recalls, and it reports the impact of school, class, ethnicity, and gender on
      agreement to participate. A total of 522 children (27% White Males [WM], 30%
      White Females [WF], 21% Black Males [BM], 22% Black Females [BF]) was available
      to recruit from 22 classes at six public schools in one district in a
      southeastern state during the 1999-2000 school year. Across classes, 45% to 95%
      of children agreed to participate (n = 376, 25% WM, 30% WF, 22% BM, 23% BF) with
      72% overall. Logistic regression indicated class as a marginally significant
      predictor of participation (p < 0.04), but failed to indicate school, ethnicity,
      or gender as significant predictors. Other specific factors that may influence
      children's participation need to be investigated and results shared to help
      improve recruitment efforts for future school-based studies.

PMID- 11962229
TI  - School nurses identify barriers and solutions to implementing a school-based
      hepatitis B immunization program.

PMID- 11962228
TI  - Peer-led, school-based nutrition education for young adolescents: feasibility and
      process evaluation of the TEENS study.
AB  - Peer education has become a popular strategy for health promotion interventions
      with adolescents, but it has not been used widely in school-based nutrition
      education. This paper describes and reports on the feasibility of the peer leader
      component of a school-based nutrition intervention for young adolescents designed
      to increase fruit and vegetable intakes and lower fat foods. About 1,000 seventh
      grade students in eight schools received the nutrition intervention. Of these,
      272 were trained as peer leaders to assist the teacher in implementing the
      activities. Results from a multicomponent process evaluation based on peer leader
      and classroom student feedback, direct classroom observation, and teacher ratings
      and interviews are presented. Results show that peer-led nutrition education
      approaches in schools are feasible and have high acceptability among peer
      leaders, classroom students, and teachers.

PMID- 11962230
TI  - Programs-that-work: CDC's guide to effective programs that reduce health-risk
      behavior of youth.
AB  - In response to requests from educators for effective programs that reduce health
      risk behavior among youth, the Centers for Disease Control and Prevention
      initiated "Programs-That-Work" (PTW) in 1992 to identify health education
      programs with credible evidence of effectiveness. CDC identified as PTW two
      programs to reduce tobacco use and eight programs to reduce sexual risk
      behaviors. Eligible programs undergo a two-step external review to examine
      quality of the research evidence and the extent to which the programs are
      practical for use by health educators. If CDC identifies a programs as a PTW on
      the basis of external review, the program is packaged and made available for
      dissemination to education and youth agencies. Communities ultimately make the
      decision about adopting a program, and CDC does not require their use. Thousands
      of educators have sought information about PTW through the CDC web site,
      informational brochures, and training.

PMID- 11962232
TI  - [Bacteriorhodopsin retains the conformation of Val69-Gly72 fragment during
      functioning].
AB  - Effect of the monoclonal antibody (MAb) 5B6 produced to the solubilized
      preparation of bacteriorhodopsin on the protein photocycle was studied to examine
      conformational rearrangements on the surface of functioning bacteriorhodopsin
      molecule. Using the methods of solid phase enzyme immunoassay, peptide phage
      display, and 1H NMR spectroscopy, we demonstrated that the epitope recognized by
      MAb 5B6 is the Val69-Pro-Phe-Gly72 fragment of the protein, with the aromatic
      ring of Phe71 and the methyl groups of Val69 participating in the binding. MAb
      5B6 exerted no significant effect on the photocycle of bacteriorhodopsin
      solubilized in Triton X-100 at pH 6.2 and 7.4, which suggested that, when
      functioning, bacteriorhodopsin retains the conformation and position of its Val69
      Pro-Phe-Gly72 fragment.

PMID- 11962231
TI  - [Photoactivatable analogues of alpha-conotoxins GI and MI and their interaction
      with nicotinic acetylcholine receptor].
AB  - Two photoactivatable analogues of alpha-conotoxin GI with the
      benzoylphenylalanine residue (Bpa) substituted for His10 or Tyr11 were
      synthesized using the method of solid-phase peptide synthesis. In addition, alpha
      conotoxin MI was chemically modified by placing an azidobenzoyl or a
      benzoylbenzoyl photo label at N alpha of Gly1 or N epsilon of Lys10. All the
      photoactivatable analogues were purified by HPLC, their structures were confirmed
      by MALDI MS, and the label positions in their molecules were localized by MS of
      their trypsinolysis fragments. All the analogues interacted with the nicotinic
      acetylcholine receptor (AChR) from Torpedo californica as efficiently as the
      native alpha-conotoxins, with the differences in the inhibition constants being
      within one order of magnitude under the same conditions. [125I]Derivatives
      prepared from all the analogues retained the ability to be bound by AChR and were
      used in the photoinduced AChR cross-linking. All the AChR subunits were found to
      be cross-linked to the photoactivatable analogues, with the linking depending on
      both the chemical nature of label and its position in the alpha-conotoxin
      molecule.

PMID- 11962233
TI  - [A structure-activity study of a catalytic antiidiotypic antibody to the human
      erythrocyte acetylcholinesterase].
AB  - The catalytic monoclonal antibody 9A8 (MA 9A8), antiidiotypic to the antibody AE
      2 (MA AE2) produced to the active site of acetyl cholinesterase from human
      erythrocytes, was subjected to a structure-function study. The specific binding
      of MA 9A8 to MA AE2 (K 2.26 x 10(9) M-1) was shown by the method of surface
      plasmon resonance, and the functional activity of MA 9A8 was demonstrated. Unlike
      acetyl cholinesterase, this antibody specifically reacted with the irreversible
      phosphonate inhibitors of esterases. A peptide map of MA 9A8 was analyzed by
      MALDI mass spectrometry. The Ser99 residue of its heavy chain was shown to be
      within the active site of the catalytic antibody. A computer modeling of the MA
      9A8 active site suggested the existence of a catalytic dyad formed by Ser99 and
      His35. A comparison of the tertiary structures of the MA 9A8 and the 17E8
      monoclonal antibody, which also exhibited an esterase activity and was produced
      to the stable analogue of the reaction transition state, indicated a practically
      complete coincidence of the structures of their presumed active sites.

PMID- 11962235
TI  - [Ion channel topography of the neuronal nicotinic acetylcholine receptor :
      pharmacochemical approaches].
AB  - Forty-three bisammonium ganglionic blockers were synthesized to study the
      structure of the ion channel of nicotinic acetylcholine receptor. The
      conformational parameters of these blockers were studied, and their effects
      toward the ganglionic transmission in situ on the sympathetic feline upper
      cervical ganglions and in vitro on the parasympathetic guinea-pig small intestine
      ganglions were determined. A model of the binding site for the bisammonium
      ganglionic blockers in the neuronal ion channel was proposed.

PMID- 11962236
TI  - [Peroxidase-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine in the presence
      of 2,4-dinitrosoresorcinol and polydisulfide derivatives of resorcinol and 2,4
      dinitrosoresorcinol].
AB  - A comparative study of the kinetics of peroxidase-catalyzed oxidation of
      3,3',5,5'-tetramethylbenzidine (TMB) in the presence of 2,4-dinitrosoresorcinol
      (DNR), its polydisulfide derivative [poly(DNRDS)], and resorcinol polydisulfide
      [poly(RDS)], substances that competitively inhibit the formation of TMB
      conversion product, was carried out. The inhibition constants, Ki for DNR,
      poly(DNRDS), and poly(RSD) were determined at 20 degrees C and pH 6.4 to be 110,
      13.5, and 0.78 microM, respectively. The stoichiometric coefficients of
      inhibition were calculated to be 0.38 and 76 for poly(DNRDS) and poly(RDS),
      respectively. In the pH range 6.4-7.0, the initial rates of the peroxidative
      oxidation of TMB, and its mixtures with DNR and poly(DNRDS) and the Ki value for
      poly(RDS) substantially decreased with increasing pH. The kinetic parameters of
      poly(RDS) (Ki 0.22-0.78 microM and f76) suggest that it is the most efficient
      inhibitor of peroxidase oxidation of TMB: in micromolar concentrations, it
      completely stops this process and can be used in EIA.

PMID- 11962234
TI  - [The production of mini antibodies against human granulocyte colony-stimulating
      factor using murine scFv combinatorial library].
AB  - To develop a phage display of single-chain antibodies (scFv), fractions of total
      cell DNA and RNA were obtained from splenocytes of naive mice. The DNA fragments
      encoding variable regions of light and heavy immunoglobulin chains were amplified
      and isolated using primers specific to the conservative regions of these genes.
      The construction of the library was based on the principle of stochastic
      combining of the DNA fragments encoding the light and heavy antibody chains with
      the DNA linker, whose structure corresponded to the (Gly4Ser)3 sequence. The scFv
      library was constructed using the E. coli TG1 strain and the phagemid vector
      pHEN1. The repertoire of the library exceeded 5 x 10(7) independent recombinant
      clones. The clones producing antibodies to the granulocyte colony-stimulating
      human factor were isolated. The affinity constants of the resulting scFv were in
      the range of 2 x 10(4) to 1.8 x 10(7) M-1.

PMID- 11962237
TI  - [A new approach to the isolation of genomic DNA samples from yeast and fungi:
      preparation of DNA-containing cell envelopes and their use in PCR].
AB  - A simple and rapid procedure for the preparation of yeast and fungal DNA samples
      useful in PCR amplification was developed. The DNA was purified from proteins,
      lipids, polysaccharides, and other impurities by their high-temperature
      extraction (in a boiling water bath) with buffer solutions containing chaotropic
      salts. Under these conditions, yeast and fungal cell envelopes remain unbroken
      and retain the original DNA and RNA that could be used for direct PCR
      amplification. We called the proposed PCR technique as the PCR using DNA
      containing cell envelopes.

PMID- 11962238
TI  - [Polar constituents of the ascidia Botryllus schlosseri].
AB  - Eighteen compounds were identified by GC-MS of their trimethylsilyl derivatives
      in n-butanolic extract from the biomass of Botryllus schlosseri. Three of them, 5
      oxoproline, 5-hydroxyhydantoin, and kinurenic acid, were found in marine
      invertebrates for the first time. In addition to cellulose, the biomass was also
      shown to contain complex water-soluble sulfated polysaccharides. These were
      extracted and fractionated, and sulfate content and monosaccharide composition
      were determined in the fractions; fucose, xylose, galactose, mannose, glucose,
      glucosamine, galactosamine, and uronic acids were found. Unlike several other
      tunicate species, Botryllus schlosseri does not seem to contain any simple
      galactan sulfate.

PMID- 11962239
TI  - [The synthesis of new photoaffinity probes on the basis of ganglioside GM1].
AB  - New photoaffine probes, photoreactive derivatives of ganglioside GM1 bearing a
      carbene-generating diazocyclopentadien-2-ylcarbonyl group at various distances
      from the carbohydrate moiety in their molecules, were synthesized.

PMID- 11962241
TI  - [The synthesis of chalcone and flavanone semicarbazones from 1,3- and 1,4
      dibenzodioxane and 1,5-benzodioxepane analogues of chalcones].
AB  - In dependence on endurance, the reaction of chalcones with thiosemicarbazide
      resulted in chalcone or flavanone thiosemicarbazones, whose structures were
      proven by 1H NMR.

PMID- 11962240
TI  - [The synthesis of cationic glycerolipid acetals containing aliphatic and
      heterocyclic bases].
AB  - 1,3-Dioxolane series cationic lipids containing residues of aliphatic or
      heterocyclic nitrogenous bases were synthesized. The bases were attached to the
      glycerol backbone either directly (piperazine) or via a spacer group through a
      thioether bond.

PMID- 11962242
TI  - [An improved method for the synthesis of flavanones].
AB  - An isomerization of 2'-hydroxychalcones into the corresponding flavanones in
      ethanol in the presence of triethylamine is described.

PMID- 11962243
TI  - [Stereospecific reduction of keto group in 3beta-triphenylmethoxy-5alpha-cholest
      8(14)-en-15-one].
AB  - The reduction of 3 beta-triphenylmethoxy-5 alpha-cholest-8(14)-en-15-one with
      lithium aluminum hydride resulted in a quantitative yield of 3 beta
      triphenylmethoxy-5 alpha-cholest-8(14)-en-15 beta-ol.

PMID- 11962244
TI  - Meat consumption and risk of stomach cancer in Uruguay: a case-control study.
AB  - We previously reported an association between meat intake and stomach cancer in
      Uruguay: in that analysis, we did not control for total energy intake. To better
      study the relationship between intake of meat and meat constituents and gastric
      cancer, we conducted a further case-control study including 123 cases and 282
      controls who were enrolled between September 1997 and August 1999. Total meat
      intake (highest tertile) was associated with an odds ratio (OR) of 4.6 [95%
      confidence interval (CI) = 2.3-9.0]. After adjustment for total energy intake and
      intake of proteins and total fat by the residuals method, the OR was 1.7 (95% CI
      = 0.7-4.0). The energy-adjusted OR for high intake of processed meat was 1.9 (95%
      CI = 1.1-3.5). Intake of fried, barbecued, and salted meat and 2-amino-1-methyl-6
      phenyl-imidazo[4,5-b]pyridine was not associated with risk of gastric cancer. The
      energy-adjusted OR of high intake of nitrosodimethylamine was 1.5 (95% CI = 0.9
      2.8). These results suggest that, in a country with elevated meat consumption,
      total energy intake and intake of proteins and fat are powerful confounders in
      the relationship between meat intake and gastric cancer risk. However, a modest
      independent effect of meat, in particular of processed meat, is suggested.

PMID- 11962245
TI  - Comparison of dietary assessment methods in a low-fat dietary intervention
      program.
AB  - The food frequency questionnaire (FFQ) is commonly utilized for assessment of
      dietary fat intake, but its validity among individuals following a low-fat diet
      is unclear. We evaluated the agreement of nutrient estimates derived from FFQ, 24
      h recall, and 3-day food records obtained from 104 participants in a randomized
      trial of a low-fat dietary intervention for women at elevated breast cancer risk.
      Comparisons were made for total calories, percent calories from fat, and total
      fat after 1 yr. Correlation was assessed using standard methods based on a null
      hypothesis of no agreement between instruments as well as by a methodology based
      on a null hypothesis that the instruments should be in agreement. With the use of
      standard methods, FFQ estimates for women on the low-fat diet were significantly
      correlated to records only for percent calories from fat (r = 0.39), whereas
      recall and record estimates were significantly correlated for all three dietary
      variables. Using the new method, we found no significant correlation between FFQ
      and either recalls or records for women following a low-fat diet but significant
      correlation between recall and record estimates for total calories (r = 0.67).
      Traditional correlation testing may overestimate the extent of agreement in
      dietary instruments among women on a low-fat diet. We found empirical support for
      the nontraditional method.

PMID- 11962246
TI  - Effect of a fish oil-enriched nutritional supplement on metabolic mediators in
      patients with pancreatic cancer cachexia.
AB  - Weight loss in advanced cancer patients is refractory to conventional nutritional
      support. This may be due to metabolic changes mediated by proinflammatory
      cytokines, hormones, and tumor-derived products. We previously showed that a
      nutritional supplement enriched with fish oil will reverse weight loss in
      patients with pancreatic cancer cachexia. The present study examines the effect
      of this supplement on a number of mediators thought to play a role in cancer
      cachexia. Twenty weight-losing patients with pancreatic cancer were asked to
      consume a nutritional supplement providing 600 kcal and 2 g of eicosapentaenoic
      acid per day. At baseline and after 3 wk, patients were weighed and samples were
      collected to measure serum concentrations of interleukin (IL)-6 and its soluble
      receptor tumor necrosis factor receptors I and II, cortisol, insulin, and leptin,
      peripheral blood mononuclear cell production of IL-1 beta, IL-6, and tumor
      necrosis factor, and urinary excretion of proteolysis inducing factor. After 3 wk
      of consumption of the fish oil-enriched nutritional supplement, there was a
      significant fall in production of IL-6 (from median 16.5 to 13.7 ng/ml, P =
      0.015), a rise in serum insulin concentration (from 3.3 to 5.0 mU/l, P = 0.0064),
      a fall in the cortisol-to-insulin ratio (P = 0.0084), and a fall in the
      proportion of patients excreting proteolysis inducing factor (from 88% to 40%, P
      = 0.008). These changes occurred in association with weight gain (median 1 kg, P
      = 0.024). Various mediators of catabolism in cachexia are modulated by
      administration of a fish oil-enriched nutritional supplement in pancreatic cancer
      patients. This may account for the reversal of weight loss in patients consuming
      this supplement.

PMID- 11962247
TI  - Effects of lyophilized black raspberries on azoxymethane-induced colon cancer and
      8-hydroxy-2'-deoxyguanosine levels in the Fischer 344 rat.
AB  - This study examined the effects of lyophilized black raspberries (BRB) on
      azoxymethane (AOM)-induced aberrant crypt foci (ACF), colon tumors, and urinary 8
      hydroxy-2'-deoxyguanosine (8-OHdG) levels in male Fischer 344 rats. AOM was
      injected (15 mg/kg body wt i.p.) once per week for 2 wk. At 24 h after the final
      injection, AOM-treated rats began consuming diets containing 0%, 2.5%, 5%, or 10%
      (wt/wt) BRB. Vehicle controls received 5% BRB or diet only. Rats were sacrificed
      after 9 and 33 wk of BRB feeding for ACF enumeration and tumor analysis. ACF
      multiplicity decreased 36%, 24%, and 21% (P < 0.01 for all groups) in the 2.5%,
      5%, and 10% BRB groups, respectively, relative to the AOM-only group. Total tumor
      multiplicity declined 42%, 45%, and 71% (P < 0.05 for all groups). Although not
      significant, a decrease in tumor burden (28%, 42%, and 75%) was observed in all
      BRB groups. Adenocarcinoma multiplicity decreased 28%, 35%, and 80% (P < 0.01) in
      the same treatment groups. Urinary 8-OHdG levels were reduced by 73%, 81%, and
      83% (P < 0.01 for all groups). These results indicate that BRB inhibit several
      measures of AOM-induced colon carcinogenesis and modulate an important marker of
      oxidative stress in the Fischer 344 rat.

PMID- 11962248
TI  - Dose-dependent promotion by phenylethyl isothiocyanate, a known chemopreventer,
      of two-stage rat urinary bladder and liver carcinogenesis.
AB  - The effects of phenylethyl isothiocyanate (PEITC) on urinary bladder and liver
      carcinogenesis were analyzed in a rat model. Diets containing 0.1%, 0.05%, or
      0.01% PEITC were administered for 32 wk to male Fischer 344 rats with and without
      pretreatment with an injection of diethylnitrosamine (200 mg/kg body wt i.p.) and
      0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for 4 wk for
      initiation. In the initiated groups, PEITC administration significantly increased
      the incidences of papillary or nodular hyperplasia, dysplasia, and transitional
      cell carcinomas at higher doses of 0.01%, 0.01%, and 0.05%, respectively,
      compared with the control group, given initiation alone, in a dose-dependent
      manner. Without initiation, administration of 0.1% and 0.05% PEITC induced simple
      and papillary or nodular hyperplasia and dysplasia in the urinary bladder. In the
      liver, induction of glutathione S-transferase placental form-positive foci was
      dose dependently enhanced by PEITC administration, but the incidences of liver
      tumors were not different among the groups. From the present experiment, we can
      conclude that > 0.01% PEITC enhances rat urinary bladder carcinogenesis, while
      weakly promoting hepatocarcinogenesis. In addition, it is suggested that > 0.05%
      PEITC has tumorigenic potential.

PMID- 11962249
TI  - Effect of dietary conjugated linoleic acid on the in vivo growth of rat hepatoma
      dRLh-84.
AB  - We examined the effect of dietary conjugated linoleic acid (CLA) on the growth of
      injected hepatoma dRLh-84 in Donryu rats. After experimental diets containing 0%
      or 2% CLA were given to male Donryu rats for 3 wk, dRLh-84 cells were injected
      into the left lobe of the hepatic capsule, and the experimental diet was
      continued. The cells formed a solid tumor > or = 1 wk after the injection, and
      thereafter the tumor grew with feeding duration. In a morphological study, this
      tumor appeared to be a low-differentiated hepatoma, and there was no remarkable
      difference in the morphology of the tumor between 0% and 2% CLA groups. Tumor
      weight was significantly higher in the 2% CLA group than in the 0% CLA group
      throughout the feeding period after the injection. Serum glutamic-oxaloacetic
      transaminase and glutamic-pyruvic transaminase activities were significantly
      higher in 2% CLA-injected rats than in 0% CLA-injected rats at 3 wk after the
      injection. CLA upregulated acyl-CoA oxidase activity, especially 1 wk after the
      injection. However, dietary CLA did not activate carnitine palmitoyl transferase
      II, which is a rate-limiting enzyme in the mitochondrial beta-oxidation pathway.
      Natural killer cell activity in the spleen tended to be higher in injected rats,
      but a significant effect of dietary CLA was not recognized. Serum interferon
      gamma and tumor necrosis factor-alpha levels were higher in injected than in sham
      rats. Moreover, these levels were higher in 2% CLA groups than in the respective
      0% CLA groups.

PMID- 11962250
TI  - Green tea and its catechins inhibit breast cancer xenografts.
AB  - Investigators have shown that green tea may decrease the risk of cancer. It is
      widely accepted that the main active component of green tea is epigallocatechin-3
      gallate (EGCG). In this study, we examined the effect of green tea on breast
      cancer growth and endothelial cells in in vitro assays and in animal models.
      Furthermore, we compared the potency of the different catechin components of
      green tea extract (GTE), including EGCG. Our data showed that mixed GTE and its
      individual catechin components were effective in inhibiting breast cancer and
      endothelial cell proliferation. In mouse experiments, GTE suppressed xenograft
      size and decreased the tumor vessel density. Our results demonstrated the value
      of all catechins and argued for the use of a mixed GTE as a botanical dietary
      supplement, rather than purified EGCG, in future clinical trials.

PMID- 11962251
TI  - Phytosterols reduce in vitro metastatic ability of MDA-MB-231 human breast cancer
      cells.
AB  - Metastasis plays a major role in morbidity and mortality from breast cancer.
      Differences in the incidence and mortality of breast cancer between societies
      suggest that environmental factors such as diet may play a role in the disease.
      Previous work from this laboratory suggests that dietary phytosterols (PS) may
      offer protection from breast cancer by inhibiting growth of the tumor and its
      metastasis in severe combined immunodeficient mice. Because metastasis is a
      multistep process, the aim of the present study was to investigate the effect of
      PS on some steps of the metastatic process: tumor cell invasion, adhesion, and
      migration. In addition, cell growth and cell cycle progression were evaluated.
      MDA-MB-231 cells were supplemented with cholesterol, beta-sitosterol, and
      campesterol. Cells were treated for 3 days with 16 microM sterol that was loaded
      on 5 mM cyclodextrin. beta-Sitosterol inhibited tumor cell invasion through
      Matrigel and adhesion of cells to plates coated with collagen I, collagen IV,
      fibronectin, and laminin compared with cholesterol treatments and controls.
      Cholesterol treatment resulted in increased adhesion to laminin and collagen IV,
      two basement membrane (BM) components that are implicated in signaling tumor cell
      invasion in this cell line. Only cholesterol treatment increased cellular
      migration. beta-Sitosterol inhibited cell growth by 70% compared with controls
      and induced cell cycle arrest at the G2/M phase. It is concluded that, among PS,
      beta-sitosterol may offer protection from breast cancer metastasis by inhibiting
      cell invasion of the BM, which may be mediated by its ability to limit the
      adhesive interaction of the tumor cell and the BM.

PMID- 11962252
TI  - S-allylcysteine, a garlic constituent, inhibits 7,12-dimethylbenz[a]anthracene
      induced hamster buccal pouch carcinogenesis.
AB  - The effect of S-allylcysteine (SAC), a water-soluble garlic constituent, on 7,12
      dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP)
      carcinogenesis was investigated in male Syrian hamstes. Forty hamsters were
      divided into 4 groups of 10 animals. The right buccal pouches of the animals in
      Group I were painted with a 0.5% solution of DMBA in liquid paraffin three times
      a week. The animals in Group II were painted with DMBA as in Group I and, in
      addition, received 200 mg/kg body wt p.o. SAC three times a week on days
      alternate to DMBA application. Group III animals received SAC as in Group II.
      Group IV animals received neither DMBA nor SAC and served as the control. The
      hamsters were killed after an experimental period of 14 wk. Measurement of lipid
      peroxidation, the antioxidant enzymes superoxide dismutase (SOD) and catalase, in
      the buccal pouch mucosa, liver, and circulation was used to monitor the
      chemopreventive potential of SAC. All hamsters painted with DMBA alone developed
      tumors identified histologically as well-differentiated squamous cell carcinomas.
      In hamsters bearing DMBA-induced buccal pouch tumors, diminished lipid
      peroxidation in the tumor tissue was accompanied by decreased activities of SOD
      and catalase, whereas in the liver and circulation, enhanced lipid peroxidation
      was associated with compromised antioxidant defenses. Administration of SAC
      suppressed the incidence of DMBA-induced HBP tumors as revealed by the absence of
      carcinomas. Histologically, only keratosis was observed. SAC modulated DMBA
      induced decreased susceptibility of the HBP to lipid peroxidation while
      simultaneously enhancing SOD and catalase activities, whereas in the liver and
      circulation, SAC decreased the extent of lipid peroxidation and significantly
      enhanced antioxidant activities. We suggest that SAC exerts its chemopreventive
      effects by modulating lipid peroxidation and enhancing antioxidant activities in
      the target organ as well as in the liver and circulation.

PMID- 11962253
TI  - Potential cancer-chemopreventive activities of wine stilbenoids and flavans
      extracted from grape (Vitis vinifera) cell cultures.
AB  - Moderate consumption of wine is associated with a reduced risk of cancer. Grape
      plant cell cultures were used to purify 12 phenols: the stilbenoids trans
      astringin, trans-piceid (2), trans-resveratroloside, trans-resveratrol, trans
      piceatannol, cis-resveratroloside, cis-piceid, and cis-resveratrol; the flavans
      (+)-catechin, (-)-epicatechin, and epicatechin 3-O-gallate; and the flavan dimer
      procyanidin B2 3'-O-gallate. These compounds were evaluated for potential to
      inhibit cyclooxygenases and preneoplastic lesion formation in carcinogen-treated
      mouse mammary glands in organ culture. At 10 micrograms/ml, trans-astringin and
      trans-piceatannol inhibited development of 7,12-dimethylbenz[a]anthracene-induced
      preneoplastic lesions in mouse mammary glands with 68.8% and 76.9% inhibition,
      respectively, compared with untreated glands. The latter compound was the most
      potent of the 12 compounds tested in this assay, with the exception of trans
      resveratrol (87.5% inhibition). In the cyclooxygenase (COX)-1 assay, trans
      isomers of the stilbenoids appear to be more active than cis isomers: trans
      resveratrol [50% inhibitory concentration (IC50) = 14.9 microM, 96%] vs. cis
      resveratrol (IC50 = 55.4 microM). In the COX-2 assay, among the compounds tested,
      only trans- and cis-resveratrol exhibited significant inhibitory activity (IC50 =
      32.2 and 50.2 microM, respectively). This is the first report showing the
      potential cancer-chemopreventive activity of trans-astringin, a plant stilbenoid
      recently found in wine. trans-Astringin and its aglycone trans-piceatannol were
      active in the mouse mammary gland organ culture assay but did not exhibit
      activity in COX-1 and COX-2 assays. trans-Resveratrol was active in all three of
      the bioassays used in this investigation. These findings suggest that trans
      astringin and trans-piceatannol may function as potential cancer-chemopreventive
      agents by a mechanism different from that of trans-resveratrol.

PMID- 11962255
TI  - Apoptotic effects of selected strains of lactic acid bacteria on a human T
      leukemia cell line are associated with bacterial arginine deiminase and/or
      sphingomyelinase activities.
AB  - The aim of the present work was, first, to analyze the apoptotic effect in vitro
      of sonicated preparations of selected strains of lactic acid bacteria on normal
      and tumor human lymphocytes. Incubation with bacterial samples led to a relevant
      time-dependent apoptotic cell death of Jurkat cells but not normal human
      peripheral blood lymphocytes. Lactobacillus brevis (CD2) samples were more
      efficient in inducing apoptosis of Jurkat cells than were samples of
      Streptococcus thermophilus (S244). In an attempt to characterize the mechanisms
      underlying these effects, we found that the apoptotic death-inducing ability of
      S244 preparations could be attributed to the ability of high levels of neutral
      sphingomyelinase activity to generate relevant amounts of ceramide, a known
      apoptotic death messenger, in Jurkat cells. On the other hand, our results
      indicate that apoptosis induced by CD2 samples could also be associated with high
      levels of arginine deiminase activity, which in turn was able to downregulate
      polyamine synthesis in Jurkat cells.

PMID- 11962254
TI  - Differential inhibition of human cancer cell proliferation by citrus limonoids.
AB  - Limonoids have been shown to inhibit the growth of estrogen receptor-negative and
      -positive human breast cancer cells in culture. The primary objective of this
      study was to test the antiproliferative activity of limonoids (obacunone 17 beta
      D-glucopyranoside, nomilinic acid 17 beta-D-glucopyranoside, limonin, nomilin,
      and a limonoid glucoside mixture), found in high concentrations in mandarin
      (Citrus reticulata Blanco), against a series of human cancer cell lines. The
      human cancer cell lines included leukemia (HL-60), ovary (SKOV-3), cervix (HeLa),
      stomach (NCI-SNU-1), liver (Hep G2), and breast (MCF-7). The growth-inhibitory
      effects of the four limonoids and the limonoid glucoside mixture against MCF-7
      cells were significant, and the antiproliferative activity of the different
      citrus limonoids was also dose and time dependent. No significant effects were
      observed on growth of the other cancer cell lines treated with the four
      individual limonoids at 100 micrograms/ml. At 100 micrograms/ml, the limonoid
      glucoside mixture demonstrated a partial inhibitory effect on SKOV-3 cancer
      cells. With use of flow cytometry, it was found that all the limonoid samples
      could induce apoptosis in MCF-7 cells at relatively high concentrations (100
      micrograms/ml). Considering the high concentration needed to induce apoptosis, it
      is unlikely that this is the primary mechanism of action for the cytotoxic
      effects seen with limonoids in this study. Further work is needed in this area to
      establish the mechanism of action of citrus limonoids on human breast cancer
      cells.

PMID- 11962256
TI  - Endothelial cells contain a glycine-gated chloride channel.
AB  - Glycine inhibited growth of B16 melanoma tumors in vivo most likely because of
      the inhibition of angiogenesis. Here, the hypothesis that the anticancer effect
      of glycine in vivo is due to expression of a glycine-gated Cl- channel in
      endothelial cells was tested. First, the effects of glycine on vascular
      endothelial growth factor-induced increases in intracellular Ca2+ concentration
      in a bovine endothelial (CPA) cell line were studied. Vascular endothelial growth
      factor (1 ng/ml) increased intracellular Ca2+ concentration, with peak values
      reaching 141 +/- 11 nM. Glycine blunted this increase dose dependently.
      Furthermore, the inhibitory effects of glycine were prevented by 1 microM
      strychnine, a glycine receptor antagonist, or when cells were incubated in Cl(-)
      free buffer. Moreover, glycine increased influx of 36Cl into CPA cells
      approximately 10-fold; this reaction was also strychnine sensitive. Furthermore,
      mRNA similar to the beta-subunit of the glycine-gated Cl- channel from spinal
      cord was identified in endothelial cells by reverse transcription-polymerase
      chain reaction. In addition, Western analysis using antibody for the glycine
      receptor demonstrated expression of the beta-subunit of the glycine receptor.
      Importantly, glycine diminished serum-stimulated proliferation and migration of
      endothelial cells. Collectively, these data indicate that the inhibitory effect
      of glycine on growth and migration of endothelial cells is due to activation of a
      glycine-gated Cl- channel. This hyperpolarizes the cell membrane and blocks
      influx of Ca2+, thereby minimizing growth factor-mediated signaling.

PMID- 11962257
TI  - Relative activities of organosulfur compounds derived from onions and garlic in
      increasing tissue activities of quinone reductase and glutathione transferase in
      rat tissues.
AB  - There is evidence that onions and garlic protect against cancer in humans. It has
      been suggested that this effect is due to the organosulfur compounds in these
      vegetables and that these substances act through induction of phase II
      detoxification enzymes. In the present studies, we have compared the ability of
      diallyl sulfide, dially disulfide, and diallyl trisulfide, compounds that are
      derived from garlic, to increase the activity of the phase II enzymes quinone
      reductase and glutathione transferase in a variety of rat tissues. We have also
      examined the onion-derived substances, dipropyl sulfide, dipropyl disulfide,
      dipropenyl sulfide, and dipropenyl disulfide, under identical conditions. Diallyl
      trisulfide and diallyl disulfide were potent inducers of the phase II enzymes.
      Dipropenyl disulfide was much less active, while little effect on enzyme activity
      was seen in animals dosed with dipropyl disulfide. Diallyl sulfide and dipropyl
      sulfide were weak inducers of quinone reductase and glutathione transferase, but
      dipropenyl sulfide was very active, with an effect similar to that of diallyl
      disulfide. It is possible that diallyl disulfide and diallyl trisulfide are
      important in the anticancer action of garlic, while dipropenyl sulfide could be
      involved in the beneficial action of onions.

PMID- 11962258
TI  - Etiology and prevention of melanoma.

PMID- 11962259
TI  - Soy milk intake and plasma sex hormones: a cross-sectional study in pre- and
      postmenopausal women (EPIC-Oxford).
AB  - Soy beans contain high levels of the isoflavones genistein and daidzein and their
      glucosides. We investigated the relationship between soy milk intake and plasma
      concentrations of estradiol, sex hormone-binding globulin, and, in premenopausal
      women, follicle-stimulating hormone, luteinizing hormone, and progesterone in a
      cross-sectional study of 636 premenopausal and 456 postmenopausal British women.
      Sixty-five percent of the women were vegetarians or vegans. Data on soy milk
      intake and other factors were obtained from a validated food frequency
      questionnaire, hormone concentrations were measured by immunoassays, and
      variations in geometric means were compared using analysis of covariance. We
      observed no statistically significant trends or meaningful associations between
      soy milk intake and circulating sex hormones. Adjusting for factors possibly
      affecting circulating hormone concentrations did not materially alter the
      results. We conclude that soy milk intake does not change plasma concentrations
      of sex hormones in pre- or postmenopausal British women who consume soy milk as a
      part of their regular diet.

PMID- 11962260
TI  - Dietary fat intake and risk of epithelial ovarian cancer: a meta-analysis of
      6,689 subjects from 8 observational studies.
AB  - The etiology of epithelial ovarian cancer is unknown. Prior work suggests that
      high dietary fat intake is associated with an increased risk of this tumor,
      although this association remains speculative. A meta-analysis was performed to
      evaluate this suspected relationship. Using previously described methods, a
      protocol was developed for a meta-analysis examining the association between high
      vs. low dietary fat intake and the risk of epithelial ovarian cancer. Literature
      search techniques, study inclusion criteria, and statistical procedures were
      prospectively defined. Data from observational studies were pooled using a
      general variance-based meta-analytic method employing confidence intervals (CI)
      previously described by Greenland. The outcome of interest was a summary relative
      risk (RRs) reflecting the risk of ovarian cancer associated with high vs. low
      dietary fat intake. Sensitivity analyses were performed when necessary to
      evaluate any observed statistical heterogeneity. The literature search yielded 8
      observational studies enrolling 6,689 subjects. Data were stratified into three
      dietary fat intake categories: total fat, animal fat, and saturated fat. Initial
      tests for statistical homogeneity demonstrated that hospital-based studies
      accounted for observed heterogeneity possibly because of selection bias.
      Accounting for this, an RRs was calculated for high vs. low total fat intake,
      yielding a value of 1.24 (95% CI = 1.07-1.43), a statistically significant
      result. That is, high total fat intake is associated with a 24% increased risk of
      ovarian cancer development. The RRs for high saturated fat intake was 1.20 (95%
      CI = 1.04-1.39), suggesting a 20% increased risk of ovarian cancer among subjects
      with these dietary habits. High vs. low animal fat diet gave an RRs of 1.70 (95%
      CI = 1.43-2.03), consistent with a statistically significant 70% increased
      ovarian cancer risk. High dietary fat intake appears to represent a significant
      risk factor for the development of ovarian cancer. The magnitude of this risk
      associated with total fat and saturated fat is rather modest. Ovarian cancer risk
      associated with high animal fat intake appears significantly greater than that
      associated with the other types of fat intake studied, although this requires
      confirmation via larger analyses. Further work is needed to clarify factors that
      may modify the effects of dietary fat in vivo.

PMID- 11962261
TI  - Dietary antioxidants, supplements, and risk of epithelial ovarian cancer.
AB  - Several studies of dietary and serum antioxidant micronutrients (vitamins A, C,
      and E and beta-carotene) suggest that higher levels may be protective for ovarian
      cancer. None of these has examined supplements. We used a food frequency
      questionnaire and additional questions on supplements to study 168 histologically
      confirmed epithelial ovarian cancer cases, 159 community controls, and 92
      hospital-based controls. Antioxidant consumption from diet or supplements was
      calculated in milligrams or international units per day. In multivariate analyses
      using only community controls, the highest levels of intake of vitamins C and E
      from supplements were protective: odds ratio (OR) = 0.40 [95% confidence interval
      (CI) = 0.21-0.78] and OR = 0.33 (95% CI = 0.18-0.60), respectively. Consumption
      of antioxidants from diet was unrelated to risk. In analyses combining
      antioxidant intake from diet and supplements, vitamins C (> 363 mg/day) and E (>
      75 mg/day) were associated with reduced risks: OR = 0.45 (95% CI = 0.22-0.91) and
      OR = 0.44 (95% CI = 0.21-0.94), respectively. Results were similar, with some
      attenuation toward the null, in analyses combining both control groups. The
      levels of vitamins C and E associated with the protective effect were well above
      the current US Recommended Dietary Allowances. These findings support the
      hypothesis that antioxidant vitamins C and E from supplements are related to a
      reduced risk of ovarian cancer.

PMID- 11962263
TI  - Intermarriage. Explaining risk of keeping it in the family.

PMID- 11962262
TI  - Relationship between mineral and trace element concentrations in drinking water
      and gastric cancer mortality in Japan.
AB  - It is well known that the incidence and mortality from gastric cancer in Japan
      are the highest in the world. This is thought to be due, in part, to dietary
      habit, including a high salt intake. There are, however, no epidemiological
      reports to describe the relationship between ingestion of mineral and trace
      elements and gastric carcinogenesis. In this study, we determined the
      concentrations of 14 elements in drinking water from 34 water treatment plants in
      Aomori Prefecture, Japan, and studied how element concentrations were
      geographically associated with gastric cancer mortality rate. Gastric cancer
      mortality was calculated from the data of the Annual Aomori Health Report.
      Multiple regression analysis (stepwise method of decreasing the number of
      variables) was performed by using age-adjusted mortality of gastric cancer by
      gender as objective variables and each element concentration as an explanatory
      variable. The standardized partial regression coefficient was significant in men
      for zinc (-0.59, P = 0.004), lead (1.01, P = 0.013), strontium (1.23, P = 0.007),
      and selenium (-1.62, P = 0.004), whereas it was significant in women for lead (
      0.65, P = 0.022), strontium (0.51, P = 0.035), and gold (0.70, P = 0.019). It is
      suggested that selenium and zinc may aid in the prevention of gastric
      carcinogenesis. However, the significant relationship of sodium (a component of
      salt) to gastric carcinogenesis was not observed, although many previous
      epidemiological studies in Japan have shown this relationship.

PMID- 11962265
TI  - Midwife 2000 takes centre stage.

PMID- 11962264
TI  - Child protection. Cry for help.

PMID- 11962266
TI  - Ethics. To die for.

PMID- 11962267
TI  - Attention Deficit Hyperactivity Disorder. Health visitors can help parents get a
      grip.

PMID- 11962268
TI  - Ethnic minorities. Black and blue? ME too.

PMID- 11962269
TI  - Should nurses who work in health promotion retain the title 'nurse'?

PMID- 11962271
TI  - Spring clean for nursing standards.

PMID- 11962274
TI  - A tale of caring babies and angelic bathwater.

PMID- 11962275
TI  - Here, there, everywhere.

PMID- 11962277
TI  - Managers must now be instructed to pay midwives at a minimum F grade.

PMID- 11962276
TI  - When the pressure's too much.

PMID- 11962279
TI  - In my new hospital, auxiliaries undertake procedures they are not trained to do.
      Am I accountable?

PMID- 11962278
TI  - All business and no pleasure?

PMID- 11962280
TI  - Rebels with a cause.

PMID- 11962281
TI  - Managing epilepsy.

PMID- 11962282
TI  - New directions for care.

PMID- 11962285
TI  - Recording a 12-lead electrocardiogram--1.

PMID- 11962284
TI  - Managing finances. Part 4.

PMID- 11962286
TI  - They think it's all over.

PMID- 11962293
TI  - Profile. Telling Ken to stop the rot. Interview by Adrian O'Dowd.

PMID- 11962295
TI  - The write stuff.

PMID- 11962296
TI  - Dealing with the complications of upper-gastrointestinal surgery.

PMID- 11962297
TI  - What is immunonutrition?

PMID- 11962298
TI  - Preoperative fasting: is it time for a change?

PMID- 11962299
TI  - New laws on foods for special medical purposes.

PMID- 11962300
TI  - Preventing and clearing blocked feeding tubes.

PMID- 11962301
TI  - Legal and ethical aspects of feeding.

PMID- 11962302
TI  - The hungry mannequin: a training model.

PMID- 11962303
TI  - [Natural regeneration of Pinus sylvestris var. mongolica plantation on sandy
      land].
AB  - By employing comparison analysis and field survey, the natural regeneration of
      Mongolian pine plantations on sandy soil was investigated. In plantation areas
      where regeneration can take place naturally, natural regeneration of Mongolian
      pine varied temporally and spatially. Natural regeneration wasn't temporally
      continuous; it had a close relationship with autumn precipitation in particular
      years. In spatial aspect, there were three regeneration types: regeneration in
      forest gaps, regeneration on edges of a forest, regeneration under young
      broadleaf forest. There was no significant difference between the growth of
      regeneration saplings and plantation trees.

PMID- 11962304
TI  - [Insecticide resistance of different populations of white-backed planthopper,
      Sogatella furcifera (Horvath) (Homoptera:Delphacidae)].
AB  - Resistance to some insecticides used commonly in different populations of the
      white-backed planthopper, Sogatella furcifera collected from Zhejiang, Guangxi,
      Yunnan and Hainan Province in China was measured. The specific activities of some
      resistance-associated enzymes, i.e. esterase, carboxylesterase, glutathione S
      transferase and acetylcholinesterase from these populations were also measured.
      The resistant levels to malathion, methamidophos, isoprocarb and buprofezin were
      markedly higher in Yunnan and Hainan populations than in other populations, but
      considerably more heterogeneity in response to insecticides was found in Zhejiang
      and Guangxi populations. The specific activities of the enzymes were obviously
      higher in Zhejiang and Guangxi populations than in Yunnan and Hainan populations,
      and the distribution range of the enzyme activity was the widest in Zhejiang
      population, and the narrowest in Guangxi population. Finally, The relationship
      between the long-distance migration and the territorial difference in insecticide
      resistant level and activities of the enzymes in the populations of this
      planthopper was discussed.

PMID- 11962305
TI  - [Fluoride accumulation and distribution in mulberry insects near fluoride
      pollution sources].
AB  - Fluoride accumulation and the relative fluoride loading of different body parts
      in wild mulberry silkworm (Bombyx mandarina M.), mulberry geometrid (Pathonandria
      atrineata B.), and mulberry silkworm (Bombyx mori L.) near fluoride pollution
      sources were studied. Comparison of the fluoride content of insect bodies and
      mulberry leaves showed that insects collected from polluted sites had increased
      fluoride accumulation. The digestive tract of the insect had much higher fluoride
      content than the other parts of the body and was considered to be the important
      organ of fluoride accumulation. There were also wide differences in fluoride
      accumulation between different insect species within the same polluted site. The
      highly significantly correlation between fluoride contents of wild mulberry
      silkworm, mulberry geometrid, and mulberry silkworm with that of the mulberry
      leaves on which they were collected was found.

PMID- 11962306
TI  - [Effects of organic acids on the toxicity of cadmium during ryegrass growth].
AB  - Effects of low molecular weight organic acids(oxalic acid, citric acid, and
      acetic acid) and higher molecular weight organic acid(humic acid) on the toxicity
      of Cd during ryegrass growth were studied. The results showed that Cd toxicity
      enhanced gradually with increasing the concentration of low molecular weight
      organic acids, and led to the decreasing of chlorophyll concentration in ryegrass
      plant and the biomass of ryegrass. The sequence of this influence was: oxalic
      acid < acetic acid < citric acid. On the contrary, Cd toxicity was reduced as a
      result of addition of humic acid, and the concentration of chlorophyll in
      ryegrass shoots and the biomass of ryegrass increased consequently. The
      concentration of Cd in roots and shoots of the ryegrass increased with increasing
      the concentration of low molecular weight organic acids, and the sequence of this
      influence was: citric acid > acetic acid > oxalic acids. The concentration of Cd
      decreased gradually as a result of increasing the concentration of humic acid,
      which means humic acid could reduce the toxicity of Cd on ryegrass. Furthermore,
      the concentration of Cd was higher in roots than in shoots, which indicated that
      the roots of ryegrass could prevent transport of Cd from roots to shoots and
      reduce Cd accumulation in the shoots.

PMID- 11962307
TI  - [Study on thinning to Robinia pseudoacacia forest on the Loess Plateau].
AB  - Radiation, temperature and soil moisture in the forests, the biodiversity and
      productivity of understory plants, and the growth of trees among 3 thinned 9-year
      old Robinia pseudoacacia forests (735 individuals.hm-2, 1110 individuals.hm-2,
      and 1480 individuals.hm-2) and non-thinning forest (2220 individuals.hm-2) were
      analyzed comparatively. The results showed that thinning could improve growing
      condition of trees and understory plants, so that the biodiversity and biomass of
      understory plants and producing ability of trees were increased. When the
      remaining density was 1110 individuals.hm-2, the soil moisture was increased by
      40% comparing with the non-thinning forest in whole growing seasons. The
      biodiversity and biomass of understory plants and productivity of trees were
      increased significantly. If the thinning intensity were increased continuously,
      the growth of understory plants and trees would reach the maximum and not
      increase any longer. Therefore, the thinning intensity with remaining density of
      1110 individuals.hm-2 was optimum for black locust forest in this region.

PMID- 11962308
TI  - [Treatment effect of constructed wetlands on organic matter in wastewater from
      pig farm].
AB  - Using plant species Vetiveria zizanioides and Cyperus alternifolius respectively,
      two constructed wetlands (CWS) with size of 1.0 m x 0.5 m x 0.8 m were
      established. The purifying function and its change pattern with season, influent
      concentration and hydraulic retention time (HRT) of the constructed wetlands on
      the organic matters in wastewater from a pig farm were studied throughout four
      seasons in the year. The results showed that the two CWS had very stable effects
      on the removal of COD and BOD, while the organic matters in wastewater changed.
      The removal rate of COD and BOD was 70% and 80% respectively by HRT 1-2 d in
      spring. The removal rate of COD reached 90% with the influent of COD 1000-1400
      mg.L-1 in summer. The removal rate of COD and BOD was 50-60% and 50% respectively
      by HRT 1-2 d in autumn. The removal rate of COD reached 70% with the influent of
      COD 1003 mg.L-1 in winter. There was no significant difference between two CWS in
      the removal of COD, BOD and SS. The rule of contaminants decreased with the HRT
      in CWS followed exponential function: Yt = Y0.exp(-kt). The relation between the
      concentration of contaminants in influent (x) and outflow (y) at the same HRT
      followed linear relation: y = a + bx.

PMID- 11962309
TI  - [pH of the gill micro-environment of Cyprinus carpio and its effect on the
      desorption of adsorbed Cu].
AB  - pH and CO2 content differences between fish(Cyprinus carpio) gills micro
      environment and the ambient environment were investigated using the technique
      developed by Playle. The effect of the pH change on elutriation of copper sorbed
      on gibbsite was also studied in view of possible desorption of the metal within
      the gill micro-environment. It was found that there was no pH difference around
      pH 8.0 and 0.2-0.4 unit difference was observed between the gills' inspired and
      the expired water when the ambient pH varied from 8 up to 9.5 or from 8 down to
      7.0. Similar trend was detected for CO2. More Cu adsorbed on the gibbsite can be
      removed by the acidified expired water from the fish gill micro-environment,
      comparing to the inspired water.

PMID- 11962310
TI  - [Classification, application, and creation of landscape indices].
AB  - In landscape ecology, it is very important to understand and grasp the ecological
      principles of landscape transformation. One of the research methods in common use
      is to describe landscape pattern and its transformation, and then connect
      landscape pattern with process by means of landscape indices. Based on the
      previous studies on landscape indices, some researches on the landscape indices'
      classification, descriptive ability, relationship among indices and indices'
      creation were conducted in this paper. Moreover, the general principles of
      applying landscape indices from two different levels, namely, from single index
      level and from index system level, were put forward.

PMID- 11962311
TI  - [Effects of nitrogen and calcium on polyphenol oxidase, peroxidase and leaf spot
      in carnation].
AB  - Carnation inoculated with leaf spot was cultivated under different concentration
      of nitrogen and calcium in this experiment. The result showed that the nutrition
      state [NO3- (0.024%-0.025%), Ca2+ (0.022%-0.0342%)] was helpful to keep higher
      activity of POD and PPO and enhance the carnation's resistance to the germs.

PMID- 11962312
TI  - [Change of component structure of shrubland in Tiantong region, Zhejiang Province
      under different treatments].
AB  - The community diversity of shrubland in Tiantong region, Zhejiang Province was
      measured by using the methods of species of abundance, Simpson index, Shannon
      Wiener index and community evenness index. The beta diversity between before
      treatments and after treatments was also measured by applying beta diversity
      index and similarity index. In addition, the changes of species composition and
      their importance values in the shrubland were analyzed. The results showed that
      whether in the first or second group of plots, the species composition and their
      importance values changed in varying degree. Compared with plots before
      treatments, the species diversity of shrub layer of experimented plots decreased
      while ecological dominance and community evenness were improved. By means of
      comparing beta diversity and similarity index, the results also showed that the
      species composition of experimented plots have changed to various extent.

PMID- 11962313
TI  - [Age structure and dynamics of Keteleeria davidiana var. chien-peii population in
      Guizhou Province].
AB  - Type and dynamics of age structure of Keteleeria davidiana var. chien-peii
      population and its relationship to community succession and environment were
      analyzed. The results showed that the age structures were classified into four
      types:growing, stable, initial and middle sensecent types. The survival curves
      had concave, convex, disconnected and dotted shapes. Along with development and
      succession of community, the age structure changes from growing, stabilized,
      senescent to residual type. The important factors causing change to the age
      structure were biological features of Keteleeria davidiana var. chien-peii,
      development of broad-leaved tree species, geographic isolation, and human
      disturbance.

PMID- 11962314
TI  - [Comparison of leaf decomposing rate in a headwater stream in Xiangxi River
      catchment].
AB  - With the litterbag method, the decomposition of leaf of 4 tree species growing in
      riparian forest in a headwater stream was investigated in 90 d consecutively in
      Xangxi River catchment. The results showed that the loss rate of dry weight of
      leaf differed among 4 species. The loss rate of dry weight of Pterocarya insignis
      and Cercidiphyllum japonicum was 77% and 71%, and shat of Fagus engleriana and
      Cyclobalanopsis multinervis was 43% and 42%. Using exponential equation, the loss
      process of dry weight of leaf was modeled. According to the value of constant k,
      4 species could be divide into to fast group and medium group. The invertebrate
      was also collected, and there were 22 species, belong to 3 classes, 6 orders, and
      21 families. The quantity of invertebrate differed in each tree species litterbag
      and different periods. The invertebrate was rich in number and small in body
      during early time of leaf decomposing, and it was less in number and big in body
      during middle and late time of decomposing.

PMID- 11962315
TI  - [Assistant assessment of landscape indices for general planning program of Wusuli
      River National Forest Park].
AB  - Landscape indices provide quantitative information about landscape pattern and
      predict some ecological processes. Rationality of Wusuli River National Forest
      Park' general planning program was evaluated by comparatively analyzing the
      landscape indices change. The results indicated that the number of patch
      decreased from 413 to 401, Shannon's evenness index increased from 0.755 to
      0.787, and predominant index decreased from 25.547 to 24.500. In addition, the
      network connectivity index, the network circuitry index, and landscape attractive
      power between scenic spot were increased, and the extent of landscape
      fragmentation was decreased. So, the planning would improve the landscape
      pattern, enhance ecosystem stability and landscape quality, and be useful for
      ecological protection and ecotourism development.

PMID- 11962316
TI  - [Analysis on forest plant diversity in the Three Gorges Reservoir Area].
AB  - The forest resource is rich in the Three Gorges Reservoir Area, according to the
      investigation data in the area, there are 41 kinds of forest communities, and the
      trend of the richness index, species diversity index and evenness index is not
      regular. In the coniferous forest, the trend of the richness index in different
      layer along the community is shrub > herb > tree. In the evergreen broadleaf
      forest, the trend is shrub > tree > herb. In the deciduous broadleaf forest,
      especially the typical Quercus forest, the trend is shrub > herb and tree, but in
      the herb layer and the tree layer, the trend fluctuates. The trend of the species
      diversity index is tree < herb and shrub, but in the herb layer and the shrub
      layer, the trend fluctuates. In other communities, the trend of all indices along
      the community fluctuates too. One reason may be the different natural environment
      and different growth condition of the community, and the long time strong
      disturbance of the human population is another important factor that couldn't be
      ignored.

PMID- 11962317
TI  - [Photosynthetic characteristics of three tree species seedlings in Changbai
      Mountain under different CO2 concentrations].
AB  - The photosynthetic characteristics of three-year-old seedlings of coniferous
      Pinus koraiensis and Pinus sylvestriformis and broadleaf Fraxinus mandshurica in
      open-top chambers in Changbai Mountain were studied. Seedlings were planted at
      four different conditions respectively:elevated CO2 concentration(700 and 500
      mumol.mol-1) and ambient CO2 concentration (control chamber and in open field).
      After treating of two growing seasons in the first two years, seedlings were
      continuously grown under different CO2 concentration for another eight weeks. The
      results indicated that the photosynthetic capacity of three species was enhanced
      under high CO2 concentration in the first two growing seasons. The maximum net
      photosynthetic rates and light response parameters of different tree species were
      different at the same CO2 concentration. No photosynthetic acclimation was
      observed in the third growing season except Pinus sylvestriformis seedlings grown
      under 500 mumol.mol-1 CO2. The increase or decrease of net photosynthetic rates
      and light response parameters were related to the time of CO2 treatment. Elevated
      CO2 concentration could alter the ability of utilizing strong light and low light
      of seedlings.

PMID- 11962318
TI  - [Ecological adaptability of Pennisetum centrasiaticum clones on farmland-sand
      dune ecotone of Keerqin sandy land].
AB  - The individual growth, morphology and population biomass of Pennisetum
      centrasiaticum clones at two different habitats of farmland-sand dune ecotone on
      Keerqin sandy land of Inner Mongolia were compared in this study. P.
      centrasiaticum clones had significant morphological plasticity and different
      biomass distribution pattern at different habitats. Compared with P.
      centrasiaticum clones on semi-fixed sand dunes, those on farmland-sand dune
      transitive zone had a greater leaf elongation, longer rhizomes and internodes,
      more adventitious buds, larger amount of biomass, and deeper distribution of
      underground biomass, which were closely associated with the loose texture of the
      upper soil and the rather favorable water condition of the lower soil. It is
      believed that the population can well adapt itself to the farmland-sand dune
      ecotone habitats, and thus, play an important role in fixing mobile sand in
      succession of arenaceous vegetation.

PMID- 11962319
TI  - [Analysis on competition and coexistence patterns of Aneurolepidium chinense and
      its main companion species].
AB  - In this study, transects were set in areas where Aneurolepidium chinense and its
      companion species grew together. Competition and coexistence patterns of these
      species in the ecotone were analyzed using the following measures:frequency
      distribution, spatial pattern, and pattern intensity. Patterns of A. chinense and
      its main companion species were diverse. Aggregation was the tactics for A.
      chinense to defend the foreign species' invading or disperse itself. There
      existed competition and coexistence between A. chinense and its main companion
      species. A. chinense and Phragmite communis competed and coexisted through
      suppression. A. chinense and Kalimeris interifolia coexisted through competition.
      Hierochloe glabra and Puccinellia tenuiflora competed with A. chinense through
      clonal growth. Calamagrostis epigeios was suppressed by A. chinense.

PMID- 11962320
TI  - [Population physiological indices on density-tolerance of maize in different
      plant type].
AB  - Taken maize in two plant types of compact-type and flat-type as research object,
      the relationships between density-tolerance and light distribution in population,
      indices of productivity(LAI, NAR, and CGR), and population sink-source were
      studied synthetically by means of crop growth analysis method. The results showed
      that light distribution in population was the chief index to measure density
      tolerance of different maize varieties. The kinetic rules of LAI, NAR, and CGR
      were the basic feature reflecting density-tolerance. The correspondent
      relationship in population sink-source was a comprehensive index to appraise
      density-tolerance of different maize varieties.

PMID- 11962321
TI  - [Skewness and inequality of height distribution of young Pinus sylvestris var.
      mongolica stands introduced on sandy soil with lower limited precipitation for
      tree survival and normal growth].
AB  - Based on the investigation of a transect (20 m wide and 80 m long) along a
      gradient (bottom, middle, and top) of a dune, whose height was about 5-10 m, the
      population dynamics in young Pinus sylvestis var. mongolica stands was studied.
      The results showed that both skewness and height inequality declined before the
      self-thinning process occurred. Age, initial growth status, density of the
      population, and neighborhood competition were the main factors affected height
      inequality. The location at sand dune was also an important factor, and its
      effect was more obvious than that of density.

PMID- 11962322
TI  - [Root growth in rice and its response to soil density].
AB  - Studies on root growth and vertical distribution at tillering(TL), panicle
      initiation(PI), flowering(FL) and mature(MT) stages and effects of soil
      compaction on root growth were carried out with hybrid rice of Shanyou 63 and
      65,002 in root box. The results indicated that root weight reached maximum at
      flowering stage and then decreased. With the advance of growth stage, percentage
      of deep roots(20-45 cm in soil) increased. Root weight increased at highest rate
      and deep roots formed during the period of TL to PI. With increased soil weight
      density below 20 cm, root weight and percentage of deep roots markedly decreased.

PMID- 11962323
TI  - [Effect of fertilization on the qualities of sweet pepper in greenhouse culture].
AB  - In order to study the effect of fertilization on the qualities of sweet
      pepper(Capsicum annul L) cultured in greenhouse, the experiment was carried out
      by drop irrigation. The results showed that the most sensitive organ of sweet
      pepper for nitrate was lateral branch, in which the nitrate content was highest.
      The nitrate content in leaf was lower than that in lateral branch, and in fruit,
      the nitrate content was the lowest. High fertilization of N, P and K had no
      negative influence on content of nitrate and total soluble sugars in fruit. The
      content of soluble sugars in fruit were about 50%-55% under all treatment and
      higher than that in leaf and lateral branch. Decreasing fertilization would cause
      increasing of the inosital and sucrose contents. Glucose and fructose were the
      main soluble sugars in fruit. The metabolism of carbohydrates was weakened by
      high fertilization, and it expressed as restraining the accumulation of starch
      content in leaf. The content of starch was the highest in fruit. The lipid
      content were exceed 3-4 times in the leaf than in the lateral branch and fruit,
      and perhaps, it was due to the higher content of chlorophyll in the leaf.

PMID- 11962324
TI  - [Effects of precipitation and soil moisture on N2O emissions from upland soils in
      Guizhou].
AB  - Soils of corn-rape seed rotation, soybean-winter wheat rotation and fallow land
      in Guizhou were representatively selected to study effects of precipitation and
      soil moisture on N2O emissions. Furthermore, DNDC model was used to assess the
      potential effects of variations in precipitation in future on N2O emissions from
      above lands. The results indicated that N2O emission pulses were obviously driven
      by rainfall and N2O fluxes were correlated positively with precipitation and soil
      moisture. The results from DNDC modeling showed that N2O fluxes from soils in
      summer and autumn would be correlated positively with precipitation, but N2O
      fluxes in winter and spring would slightly decrease with great change of
      precipitation.

PMID- 11962325
TI  - [Study on the ecological regions of soybean in China. II. Ecological environment
      and representative varieties].
AB  - Based on the climatic and geographical condition, cropping system and season
      sowing types and maturity group (MG) types of 256 varieties in test from total
      cultivating regions of soybean in China, six ecological regions of soybean were
      suggested. Those are: Northern single cropping, spring planting eco-region(I),
      Huanghuaihai double cropping, spring and summer planting eco-region(II), Middle
      and lower Changjiang valley double cropping, spring and summer planting eco
      region(III), Central south multiple cropping, spring, summer and autumn planting
      eco-region(IV), Southwest plateau double cropping, spring and summer planting eco
      region(V), and South China tropical multiple cropping, all season planting eco
      region(VI). The cultivating environmental condition and representative varieties
      were shown, and the characteristics of all ecological regions of soybean in China
      were also discussed in this paper.

PMID- 11962326
TI  - [Allelopathy of Ageratum conyzoides. VI. Effects of meteorological conditions on
      allelopathy of Ageratum conyzoides].
AB  - In the field, allelopathic potential of A. conyzoides correlated significantly
      with sunshine time, temperature and rainfall. Allelopathic potential of A.
      conyzoides grew in favorable combinate condition of temperature, rainfall and
      sunshine time, allelopathic potential of A. conyzoides reduced, and vice versa.
      Allelopathic potential of A. conyzoides decreased because of favorable growing
      seasons in spring and summer. On the contrary, autumn and winter were unfavorable
      growing seasons, and the allelopathic potential of A. conyzoides increased. Under
      laboratory experiments, the volatile oil of A. conyzoides made the tested plants
      not survive at high concentrations of 300 micrograms.ml-1, but volatile oil of A.
      conyzoides inhibited the tested plants slightly at low concentrations of 60
      micrograms.ml-1. However, under high or low temperatures and shading conditions,
      inhibitory effects of allelochemicals of A. conyzoides on tested plants
      intensified significantly at low concentration. It revealed that under
      unfavorable growing conditions, tested plants resistant ability to the
      allelochemicals of A. conyzoides decreased. When A. conyzoides and tested plants
      both grew under unfavorable meteorological conditions, allelopathic potential of
      A. conyzoides increased, and the tested plants resistant ability to
      allelochemical decreased. Thus, other plants growing among A. conyzoides in
      natural community were difficult to grow, and it was relatively improved
      competitive ability of A. conyzoides in natural communities. Joint effect of
      allelopathic potential and some meteorological factors such as sunshine time,
      temperatures, and rainfall was one of the important factors that A. conyzoides
      was dominated in natural communities.

PMID- 11962327
TI  - [Landscape pattern analysis based on boundary characteristics].
AB  - Through boundary number to the length distribution spectrum analysis, the
      relationships between boundary number-length and fragmentation of landscape and
      element were discussed. Landscape pattern indices such as diversity, evenness,
      heterogeneity, and spatial complicity were calculated based on boundary number
      and cumulative length, and these indices were compared with those based on
      element area proportion. The results indicated that the fast urbanization process
      caused complication of boundary element distribution pattern and simplification
      of layer structure. The distribution function parameter alpha could reflect
      landscape fragmentation properly, and the landscape pattern indices based on
      boundary characteristics was an useful supplement for traditional pattern
      analysis.

PMID- 11962328
TI  - [Effects of different mycorrhizal fungi on physiological metabolism of tobacco
      seedlings].
AB  - Tobacco seedlings were inoculated with VA mycorrhizal fungi in natural soil. The
      results showed that compared with the control, the contents of nitrogen,
      phosphorus, potassium and chlorophyll, nitrate reductase activity, and protein in
      leaves were higher, malondialdehyde(MDA) and hydrogen peroxide(H2O2) decreased,
      while the activities of superoxide dismutase(SOD), catalase(CAT), and
      peroxidase(POD) increased. Meanwhile, seedlings were inoculated with two strains
      of ectomycorrhizal fungi respectively, and the above physiological indices
      trended the same changes. Moreover, the effect of strain Calvatia lilacina was
      higher than that of VA mycorrhizal fungi.

PMID- 11962329
TI  - [CCA of water beetles' distribution and environmental factors in lentic samples
      of north Changbai Mountain].
AB  - The relationship between 28 species water beetles in 12 lentic samples and
      environmental factors of North Chang-bai Mountain was studied by Cononical
      Correspondence Analysis (CCA). The results showed that degree of underwater humus
      and altitude are the major factors correlated with beetles distribution, and the
      correlation coefficients of environmental factors and axes of CCA were 0.8371 and
      0.7206 respectively, while water temperature and plant density also had certain
      effects. Under the influence of environmental factors, the water beetles'
      populations were different in different habitat. Coelambus impressopunctatus,
      Colymbetes magnus, Helophorus browni, Haliplus spp. distributed in deep water
      pool. Water temperature was not important for those beetles. Ilybius sp. and
      Limnebius glabriventris correlated with altitude and humus.

PMID- 11962330
TI  - [Main factors influencing the growth of planktonic bacteria in fish pond
      ecosystem].
AB  - Focused on the main factors influencing the growth of bacteria in fish pond
      ecosystem, the variation of abundance in bacterial culture, the effects of
      substrate on bacterial growth, nutrient uptake and mineralization, the effects of
      bacterivorous predator and water temperature on bacterial growth were
      investigated in this paper. The results showed that the growth of bacteria and
      its uptake of C and N were enhanced by application of inorganic phosphorus into
      the water, but not by application of organic carbon and nitrogen, and that the N
      mineralization was increased by adding organic nitrogen, indicating that the
      bacterial growth was limited by inorganic P in the substrate, not by organic C
      and N. Among the five test groups, predator bacteria had the slowest growth rate,
      being lower than the control by 6.26-15.4%. The abundance of bacteria, its number
      increment and growth rate in the fish pond were found to be positively correlated
      with water temperature in different seasons. In addition, at higher temperature,
      the positive effects of nutrient application on bacterial growth were enhanced,
      while the negative effects of predator bacteria on bacterial growth were
      weakened.

PMID- 11962331
TI  - FISH in cancer diagnosis and prognostication: from cause to course of disease.
AB  - The last 20 years have witnessed an astounding evolution of cytogenetic
      approaches to cancer diagnosis and prognostication. Molecular techniques and, in
      particular, nonisotopically-labeled nucleic acid probes and fluorescence in situ
      hybridization (FISH)-based techniques have replaced the costly and potentially
      dangerous radioactive techniques used in research and the clinical detection of
      genetic alterations in tumor cells. Fluorescent DNA probes also enabled the
      screening for very subtle chromosomal changes. Clinical laboratories now choose
      from a growing number of FISH-based cytogenetic tests to support physician's
      diagnoses of the causes and the course of a disease. Depending on the specimen,
      state-of-the-art FISH techniques allow the localization and scoring of 10-24
      different targets and overcome previous problems associated with target
      colocalization and detection system bandwidth. FISH-based analyses have been
      applied very successfully to the analysis of single cells and have demonstrated
      the existence of cell clones of different chromosomal make-up within human
      tumors. This information provides disease-specific information to the attending
      physician and should enable the design of patient-specific protocols for disease
      intervention.

PMID- 11962332
TI  - Detection of chromosomal imbalances in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is the most common malignant tumor of the liver. The
      discrimination between well-differentiated hepatocellular carcinoma and reactive
      lesions and benign tumors may be difficult, especially when performed on the
      basis of needle biopsies. A promising means of solving this problem is provided
      by chromosomal analysis of imbalances in hepatocellular carcinoma. This article
      describes the different approaches to ascertain differential diagnosis by
      chromosomal studies in a reliable and cost-effective manner. It is shown that in
      situ hybridization techniques provide a reliable means of defining chromosome
      alterations. These techniques allow the detection of genetic gains and losses of
      defined chromosomes in a histopathological context and can serve as a helpful
      tool in establishing diagnosis of liver cell proliferation.

PMID- 11962333
TI  - Prognostic markers in prostate cancer.
AB  - In this review, a series of relatively well-documented ancillary biomarkers and
      emerging molecular assays are evaluated for their relative ability to predict
      prognosis in prostate cancer. Prognostic factors that have achieved widespread
      use and classified as Category I by the College of American Pathologists Solid
      Tumor Prognostic Factor Consensus Conference are compared with newer tests that
      are beginning to be used in clinical practice (Category II) and emerging
      molecular-based assays that have yet to be widely validated in the published
      literature or clinical trials (Category III).

PMID- 11962334
TI  - Molecular detection and characterization of Neisseria meningitidis.
AB  - Immediate management of meningococcal infections is a medical emergency that
      requires rapid identification and typing of bacterial strains. Isolation of
      Neisseria meningitidis is hindered by early antibiotic treatment. Molecular
      (nonculture) methods of diagnosis and characterization of N. meningitidis permit
      to overcome this failure. This bacterium is highly variable due to frequent
      horizontal DNA exchange between strains. Molecular approaches of typing allow a
      reliable tracking of meningococcal strains and a powerful epidemiological
      analysis.

PMID- 11962335
TI  - Diagnosis of MDR-TB: a developing world problem on a developed world budget.
AB  - The resurgence of tuberculosis worldwide has been accompanied by an increase in
      the incidence of multidrug-resistant tuberculosis on all continents. While
      significant advances have been made in the rapid and accurate diagnosis of
      Mycobacterium tuberculosis, the molecular biology methods used in the research
      laboratory to elucidate the mechanisms of drug resistance cannot be transferred
      to the centers delivering patient care. These methods require skilled operators,
      cumbersome protocols and extravagant expense. A number of companies that already
      have a large investment in M. tuberculosis diagnostics are adapting their high
      throughput technology to drug susceptibility testing. These methodologies are not
      applicable to the developing world not only because of the costs involved but
      through a lack of infrastructure that is required to operate these machines and
      deliver specimens to the point of testing. Alternative technologies for drug
      susceptibility testing that do not rely on an investment in expensive hardware
      are presented and their potential use in the field is discussed. Though still
      relatively expensive to perform, these newer innovations may lead to the
      development of less intricate technologies that have universal application and
      begin to move away from our obsession with molecular-based diagnostics to produce
      on all encompassing gold standard.

PMID- 11962336
TI  - Molecular diagnosis of facioscapulohumeral muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited
      neuromuscular disorder after Duchenne muscular dystrophy and myotonic dystrophy.
      The gene underlying FSHD was mapped to chromosome 4q35 in 1990 and was shown to
      be closely linked to locus D4F104S1. Although D4F104S1-associated deletions are
      closely associated with FSHD, the identity and location of the FSHD gene (or
      genes) still remain elusive, as does the mechanistic basis of the disease. In
      addition, although approximately 5% of FSHD families fail to exhibit linkage to
      4q35, a putative second locus remains unidentified. The search for the FSHD gene
      has been hampered both by sequence homologies between the 4q35 candidate region
      and other chromosomal regions and by the presence of many highly repetitive
      sequences. Molecular diagnosis for FSHD is usually offered with 98% accuracy but
      because of its complexity, a much more simple test would be preferable. Indeed,
      the identification of the FSHD gene itself should potentiate major improvements
      in diagnostic testing.

PMID- 11962337
TI  - Quartz crystal analytical sensors: the future of label-free, real-time
      diagnostics?
AB  - Acoustic sensor technologies have a long and prestigious history. However, liquid
      phase applications based upon thickness shear mode transducers are a relatively
      recent addition but are nonetheless being rapidly accepted as a broad usage
      analytical platform upon which to carry out label-free, real-time chemical,
      biological and pharmaceutical assays. This article discusses the development of
      thickness shear mode devices, current technologies, with a focus on the breadth
      of application and the future potential of the technique within the
      pharmaceutical and biochemical industries.

PMID- 11962338
TI  - Gold nanoparticles as novel label for DNA diagnostics.
AB  - The growing interest in DNA diagnostics, especially in combination with the need
      for highly-paralleled and miniaturized hybridization assays, is today addressed
      by fluorescence DNA chips. Fluorescence detection is approved and highly
      developed, however, it has also problematic aspects, e.g., the low stability of
      the dyes, the influence of the physicochemical environment onto the signal
      intensity and the expensive set-up for detection. A novel detection scheme based
      on metal nanoparticles was proposed to overcome these problems and is discussed
      in this review.

PMID- 11962339
TI  - Molecular diagnostics: impact upon cancer detection.

PMID- 11962340
TI  - Fujirebio Diagnostics to develop cancer diagnostics.

PMID- 11962341
TI  - New clinical data further supports accuracy of the Vysis UroVysion test.

PMID- 11962342
TI  - Chiron's procleix HIV-1/HCV assay receives FDA approval.

PMID- 11962343
TI  - Quest diagnostics announces improved HEPTIMAX hepatitis C viral load test.

PMID- 11962344
TI  - AcroMetrix announces first HCV Genotyping Proficiency Program.

PMID- 11962345
TI  - Blood test may help discourage doping.

PMID- 11962346
TI  - Molecular detection of gene mutations and methylation abnormalities: applications
      in solid tumor diagnosis.
AB  - As our knowledge of the genetic and epigenetic abnormalities initiating and
      contributing to tumorigenesis grows, so too does the scope for earlier detection
      of cancer in patients. This bears an immense potential impact on the clinical
      management of patients with or at risk of solid tumors, since arguably the
      greatest problem facing clinicians is late presentation. PCR-based tests have
      been developed to detect mutant or hypermethylated alleles in exfoliative
      material and plasma/serum, enabling risk-assessment and early detection programs.
      Although there are certain limitations, a number of studies have already
      demonstrated the feasibility and reliability of molecular screening in solid
      tumors, including colorectal and lung cancers and such molecular approaches may
      soon be used routinely to detect precursor lesions and early-stage cancer.

PMID- 11962347
TI  - Anthrax and anthrax anxiety: Sverdlovsk revisited.

PMID- 11962348
TI  - Mixed outbreak of parainfluenza type 1 and influenza B associated with tourism
      and air travel.
AB  - BACKGROUND: A preseasonal outbreak of influenza-like illness was reported in a
      tourist group that had returned from Ireland to the United States on October 1
      and 2, 1999. The authors investigated to determine the timing, extent, and nature
      of the outbreak. METHODS: A cohort study was conducted among the entire group.
      Cases were defined as illness occurring among tour members who experienced cough
      or sore throat with onset from September 29 through October 5. Nasopharyngeal and
      throat cultures were examined for respiratory viruses. RESULTS: Eighteen (60%) of
      the 30 tourists were ill; the majority (66%) of cases had onset of illness within
      1 day of departure from Ireland. Human parainfluenza virus type 1 was isolated
      from six cultures, and influenza B from three. The attack rate was 100% among the
      eight persons 65 years of age or older versus 45% among the 22 persons younger
      than 65 years (P = 0.01). CONCLUSION: International travellers, particularly
      older persons and members of organized tour groups, may experience increased
      risks for respiratory viral infection. The recognition and containment of
      imported infectious diseases depend on prompt reporting and epidemiologic
      investigation.

PMID- 11962349
TI  - Systematic review of combination antiretroviral therapy with didanosine plus
      hydroxyurea: a partial solution to Africa's HIV/AIDS problem?

PMID- 11962350
TI  - Theresa's angel: when your best isn't enough.

PMID- 11962351
TI  - Despite good tools, we do not effectively reduce travelers' hepatitis A.

PMID- 11962353
TI  - Could prolonged air travel be casually associated with subclavian vein
      thrombosis.
AB  - BACKGROUND: Air travel associated with venous thromboembolism has recently
      achieved public awareness due to intense media coverage. The interest has focused
      on deep vein thrombosis (DVT) of the lower limbs with pulmonary embolism. The
      World Health Organization (WHO) is planning several international multicenter
      trials to study the problem and, if it exists, try to find a means for
      prevention. METHODS: This is a case presentation of acute venous thromboembolism
      of the upper limbs associated with long-haul flights. Five patients were admitted
      to Straub Hospital in Honolulu after 5 to 10 hours flight. RESULTS: Patient 1 had
      a previous shoulder injury with DVT; patient 2 had chronic atrial fibrillation;
      patients 3 and 5 had clavicular fractures; and patient 4 had a subclavian vein
      compression. CONCLUSION: It is not possible to draw any conclusions about the
      association between air flights and subclavian vein thrombosis from this small
      retrospective case study. Our objective was to indicate the possibility of such a
      relationship.

PMID- 11962352
TI  - Ineffectiveness of the current strategy to prevent hepatitis A in travelers.
AB  - BACKGROUND: Each year, a large number of Canadians travel to regions of the world
      where hepatitis A remains endemic. Many of these travelers are not immune and the
      current preventive strategy relies wholly on self-referral to a travel clinic.
      All of the costs associated with such a visit are assumed by the traveler. We
      estimated the effectiveness of this strategy. METHODS: This case-control study
      included 108 travel-related hepatitis A cases with onset of disease between 1997
      and 1999 and 620 controls who traveled during the same period. RESULTS: Hepatitis
      A was strongly associated with high-risk travel (Odds Ratio = 7.2, 95% Confidence
      Interval 1.76-29.4), but only 7% of cases were found in this category. The risk
      of hepatitis A was 5 times lower in travelers who visited a travel clinic than in
      those who did not (80% efficacy). However, only 14% of the controls visited a
      travel clinic. As a result, the effectiveness of the current strategy is
      estimated to be 11% (80% of 14%). CONCLUSIONS: Hepatitis A in travelers can be
      prevented effectively by attendance at a travel clinic. Unfortunately, most
      travelers do not visit such clinics prior to departure. Even if all high-risk
      travelers were to visit a travel clinic and receive vaccination, this would have
      negligible impact on the number of travel-related hepatitis A cases
      (approximately 7% reduction). The current strategy for the prevention of
      hepatitis A in travelers is ineffective and should be reexamined.

PMID- 11962354
TI  - Iowa's dental workforce. What a difference a decade makes!!

PMID- 11962355
TI  - Ominous sign of the times.

PMID- 11962356
TI  - Tilting the balance of care.

PMID- 11962357
TI  - The power of nursing.

PMID- 11962358
TI  - Bibliography. Current world literature. Genetics and molecular biology.

PMID- 11962489
TI  - Collaboration on the rice genome.

PMID- 11962488
TI  - Why finishing the rice genome matters.

PMID- 11962490
TI  - Regulating natural health products.

PMID- 11962491
TI  - Regulating natural health products.

PMID- 11962493
TI  - The giant kidney worm.

PMID- 11962492
TI  - Type-1 steroid 5 alpha-reductase is functionally active in the hair follicle as
      evidenced by new selective inhibitors of either type-1 or type-2 human steroid 5
      alpha-reductase.
AB  - Steroid 5 alpha-reductase catalyzes the reduction of testosterone (T) into the
      very potent androgen dihydrotestosterone (DHT). The different tissue expression
      patterns of the two isoforms of 5 alpha-reductase, namely type-1 and type-2 5
      alpha-reductase (5 alpha-R1 and 5 alpha-R2, respectively), have prompted studies
      directed towards the synthesis of selective 5 alpha-R1 or 5 alpha-R2 inhibitors.
      In this present work, we have performed a structure/activity study on the
      inhibitory potential of indole carboxylic acids against hair follicle 5 alpha
      reductase activity. We have demonstrated that this class of molecules were potent
      inhibitors of either 5 alpha-R1 or 5 alpha-R2 or both depending on (i)
      substituents in positions 4, 5 or 6 and (ii) the presence of a free carboxylic
      group. We have also found that only 5 alpha-R1 or 5 alpha-R1/R2 inhibitors were
      able to inhibit 5 alpha-reductase activity in plucked hairs from female
      volunteers or in freshly isolated female hair follicles, selective 5 alpha-R2
      inhibitors being inactive.

PMID- 11962494
TI  - Prevention of human deconditioning during prolonged immersion in water.
AB  - A 56-day immersion experiment in which two subjects participated was carried out.
      During the experiment the preventive effect of periodic acceleration combined
      with exercise and water-salt intake was assessed. Simulating an increased
      gravitational field, exposure to acceleration increased the static component of
      the load upon the musculo-skeletal system, increased the gradient of the blood
      hydrostatic pressure, activated mechanisms responsible for the venous return to
      the heart, stimulated systems regulating antidiuretic and antisodiumdiuretic
      reflexes. Involvement of these mechanisms restored haemodynamic parameters, fluid
      electrolyte balance and blood coagulability. The prophylactic effect of
      acceleration was enhanced if combined with exercise and supplemented water-salt
      intake.

PMID- 11962495
TI  - Circulatory adaptive reactions under hypergravity in normal and cold
      environments.
AB  - Rats subjected to various levels of +Gz acceleration exhibited an increased blood
      concentration of noradrenalin and adrenalin, indicative of a sympatho-adrenergic
      reaction. Under the same conditions, from plasma determinations, and by
      histochemical examination of the supra-optic nucleus, an increased antidiuretic
      response was noted. This response was reduced in cold environment.

PMID- 11962496
TI  - Food and oxygen requirements for growing mice and turtles after
      hypergravitational development.
AB  - Although development of mice and turtles, both low-payload animals, can be
      influenced by ambient gravitational intensity, little is known regarding the
      influence of either their growth or their gravitational history upon life-support
      requirements. A 25-g male Box Turtle (Terrapene carolina, optimally growing at 30
      degrees C and 1 G to double its size in 7 weeks) exhibits daily requirements of
      oxygen (100 ml) and food (200 mg, dry) which are only 3% of the requirement for a
      mouse (Swiss Webster, centrifuged at 22 degrees) of comparable size and growth
      rate. These requirements grow in proportion to the turtle's (body mass)0.9 and to
      the mouse's (body mass)0.5. After development at hypergravity g (of from 1.5 to 5
      G expressed in multiples of the earth's gravity) there is a one-day delay for
      turtles but an immediate change for mice in these requirements upon return to 1
      G. Although both show a decreased oxygen intake, the drop is greater for turtles
      (equalling g -0.4 of the baseline value, as corrected for body size, after return
      from 75 days exposure against g-0.08 for mice after 1-13 days exposure); the food
      intake drops for turtles (varies as g-1) while it rises for mice (varies as
      g0.6).

PMID- 11962497
TI  - Body size and chronic acceleration.
AB  - Body composition studied as a function of acceleration (1-4.7 G) in mice and rats
      showed fat-free body mass (FFBM) to be a predictable function of G-force while
      corroborating the known lability of body fat. Of nine studied components of FFBM
      only skeletal muscle, liver and heart contributed to the observed changes induced
      by delta G. (Body water /FFBM) was independent of delta G. When FFBM (as a
      percentage of 1 G controls) was plotted against G for mice, rats and monkeys (1
      4.7 G) and men (0-1 G), the mass of the fat-free compartment passed through a
      maximum at 1 G. The data distribution in the figure suggested possible effects of
      body size and of age.

PMID- 11962498
TI  - Gravitational influences upon the maintenance requirements of rabbits.
AB  - The gravitational component of the feed requirement for the maintenance of body
      mass has been reported previously for chickens. Similar measurements are reported
      here for chronically accelerated Polish rabbits, which have mature body masses
      around 2 kg, approximately the same as for the single-comb white Leghorn chickens
      used in the earlier experiments. The gravitational influences upon the
      maintenance requirement and upon body composition were found to be essentially
      similar for rabbits and chickens, indicating a general phenomenon for small
      homoiotherms. The principal response in both groups is a greater feed maintenance
      requirement which increases linearly with the applied acceleration field. The
      nature of this response is similar to that which follows lesioning of the lateral
      hypothalamus in rats, though no causal connection between the two phenomena is
      necessarily implied by these present studies. In monkeys a qualitatively
      different response of increased body fat is observed.

PMID- 11962499
TI  - The effect of increased gravitational stress on bone.
AB  - To assess the effects of an altered gravitational state on the physical
      properties of bone, fifteen sexually mature chickens were centrifuged for 18
      weeks. The gravitational forces were gradually increased to allow the chickens to
      adapt to the increased load. For the last 4 weeks of the experiment, the animals
      were subjected to a force of 3 x gravity. After sacrifice the tibias were removed
      and fractured in torsion. Bone diameters, cortical thickness and ash content of
      the tibias were determined. Histological preparations of the bone specimens were
      also examined. When the centrifuged animals were compared with control chickens
      of comparable size and weight, there was no significant change in bone strength
      or fracture pattern, although the centrifuged birds had smaller mid-tibial shaft
      diameters and thicker cortices. The mean percentage bone ash for the centrifuged
      birds was 68.2% which is an accepted value for dry bone ash of adult chickens.
      Bone density was the same for both centrifuged and control birds. The birds lost
      an average of 465 grams of body mass during their 18 weeks on a centrifuge.

PMID- 11962500
TI  - Biological experiments on the orbital station Salyut 4.
AB  - Two series of experiments were carried out on the orbital station Salyut 4: one
      series consisted of two experiments (30 and 62 days respectively) designed to
      study the effect of space-flight factors on the growth and development of
      Drosophila melanogaster, strain D-32, and the second series consisted of two
      experiments (24-33 days) designed to study the effect of space-flight factors on
      the growth and development of the dwarf pea, variety "Pioneer". Analysis of the
      progeny from flies exposed to space flight showed an increase in the rate of
      visible mutations for y, ct, w and vg loci over those observed in the earth
      control. Space flight factors produced no noticeable effect on the first growth
      stages of pea plants. Later on growth stopped and most of the plants died under
      weightless conditions at the age of 2-3 weeks. Possible causes of their death
      during flight are discussed on the basis of anatomo-morphological, cytological
      and biochemical analyses of experimental and control plants.

PMID- 11962501
TI  - Chronic acceleration in plants.
AB  - Since this subject was last reviewed (at the Symposium on Gravity and the
      Organism, 1967), relatively little new work on hypergravity effects on plants has
      appeared. Centrifugation has been used widely for separation of cellular
      components, but only occasionally as a primary environmental condition. With
      increasing magnitude of accelerative forces, the following effects have been
      reported by a number of authors working with many different plants. In the range
      2-25 g, auxin transport and geotropic response in coleoptiles are increased and
      growth is stimulated. From 25 to 500 g, coleoptile growth is reduced and some
      morphological changes may be seen. At 1000-2500 g, root formation in willow
      cuttings increases. From 1000 g upward, cytoplasmic stratification occurs and
      seed germination decreases. Between 200 and 15000 g, chromosome damage has been
      observed. Algal cell polarity may be reversed at 5000 to 20000 g. Above 30000 g,
      the response of some cells to gibberellic acid is halted. Permanent morphologic
      changes in Escherichia coli are produced at 110000 g. Some plant cells have
      survived 176000 g for 20 hr.

PMID- 11962502
TI  - Effect of weightlessness and of artificial gravity on irradiated lettuce seeds.
AB  - In our previous studies on board the artificial earth satellite Cosmos 368, the
      cosmic apparatus Zond 8 and the orbital station Salyut it has been demonstrated
      that space-flight factors (SFF) have a definite effect on poorly active
      biological systems, such as dry lettuce seeds. The technical possibilities on
      board the biosatellite Cosmos 782 (the availability of an on-board centrifuge)
      allowed us to obtain some new data concerning the mechanisms of the SFF effects.
      Irradiated seeds of lettuce (Lactuca sativa L.) were exposed in space flight for
      22 days either to weightlessness conditions only or to a centrifugal field. Data
      have been obtained characterizing the cytogenetical and physiological processes
      in seeds of various series of the experiment. An attempt is made to analyse the
      role of individual SFF in the changes observed.

PMID- 11962503
TI  - Effects of weightlessness, space orientation and light on geotropism and the
      formation of fruit bodies in higher fungi.
AB  - The effect of flight factors on the growth and development of the fruit bodies of
      the higher fungus Polyporus brumalis is investigated under the conditions of an
      experiment on the earth satellite Cosmos 690. Fungi were grown on the earth under
      conditions of simulated flight and transit; fungi were also grown in the
      laboratory at a temperature similar to that in flight, at various orientations
      and under various illuminations. Polyporus brumalis grows well on wort; it forms
      fruit bodies on long pedicles (up to 25 cm) and possesses a strongly marked
      negative geotropism. Investigations have shown that the formation of hymenium and
      pileus is induced by definite time exposures to light. In darkness the formation
      of fruit bodies takes place, but without formation of hymenium and pileus, and
      the rate of growth is greater than in light. The strong negative geotropism
      remains in fruit bodies when developed in darkness and with test-tubes in a
      vertical position. When the test-tube orientation is changed the pedicles change
      direction in darkness as well as in light. In maintaining their negative
      geotropism the fruit bodies bend with changes of space orientation. In the
      absence of gravity a disorientation of fruit bodies takes place, and the pedicles
      are strongly twisted into a spiral or into a ball. A flattened type of fruit body
      can also occur. Such a picture of growth and formation was not observed in
      control samples. Thus, there is a strong dependence of the formation of the fruit
      body of Polyporus brumalis on space orientation, gravity and light.

PMID- 11962504
TI  - Growth-rate periodicity of Streptomyces levoris during space flight.
AB  - Streptomyces levoris Kras was used is an experimental test micro-organism during
      the Apollo Soyuz Test Project to study alternating vegetative mycelial and spore
      ring periodicity during space flight. Four cultures were launched in each of the
      spacecrafts (Apollo and Soyuz). During the joint space-flight activities, two
      cultures from each spacecraft were exchanged. Selected duplicate cultures were
      maintained as controls in both the USA and the USSR. Spore ring morphology was
      periodically documented by photographing the specimens at approximately 12-hr
      intervals during the pre-, in-, and post-flight periods of the experiment. A
      decreased growth-rate periodicity in all but one of the eight space-flight
      cultures was in part attributed to the reduced temperature in the spacecraft. One
      of the eight cultures grew at a faster rate in the reduced temperature
      environment of Apollo than did the ground controls. Three of the space-flight
      cultures developed double spore rings during the immediate post-flight period.
      This anomaly was attributed to re-entry into the earth's gravity. The absence of
      spores in portions of one ring formed during space flight may have been caused by
      nutritional defects or media abnormality. Extensive studies will be required to
      elucidate the cause of this detect with certainty. There was no visible evidence
      of wedges in the cultures which would suggest naturally occurring or radiation
      induced mutagenic alteration during space flight.

PMID- 11962505
TI  - Apollo-Soyuz Test Project on biorhythm of zone-forming fungi: results of
      experiments.
AB  - Biorhythmic changes in spore (correction of sport) formation in the Pushchino
      strain of Actinomyces levoris Kras cultures on board Soyuz and Apollo during
      their joint flight in July 1975 are analysed and compared with control cultures
      on earth. Biorhythm changes during the flight period showed up as both a slowing
      down (most cultures) and, in a few cases, an acceleration of the rhythm. During
      the post-flight period both acceleration and slowing down of the rhythm were also
      observed. In cultures that were exchanged during the docking of the spaceships a
      slowing down of the rhythm on Apollo and acceleration of the rhythm on Soyuz were
      observed. A pronounced ring deformation, in response to landing, was observed
      only in the cultures on Soyuz. It was, however, different for the cultures that
      had been passed from Apollo and for those constantly on Soyuz. In five places, on
      four rings formed during the flight, local changes in spore formation occurred.
      The rhythmical disturbances observed are discussed in terms of possible effects
      of different temperatures, the absence of usual geophysical periodicities
      synchronizing the rhythmicity, or their shifting after landing, local radiation
      and other factors.

PMID- 11962506
TI  - Turkey and its international relations in the history of medicine.
AB  - My discussions with ISHM members have disclosed considerable interest in the
      history of the relations that Turkey and its medicine have had with other
      countries. Dr Lellouch, the secretary of ISHM, originally suggested that I
      address the subject of Turkish-French relations by means of an essay in Vesalius.
      This led me to consider a wider ranging paper on Ottoman-European relations. For
      completeness, I have briefly covered the Turkish peoples' relations with the
      Eastern, as well as the Western World. The overall aim of this article is to act
      as a stimulus for further discussion on the international relations in health
      sciences between Turks and other peoples.

PMID- 11962507
TI  - The human skin: a meeting ground for the ideas about macrocosm and microcosm in
      ancient and Medieval and Greek literature.
AB  - We have been interested in the cleansing capacity of skin during the recent
      years. In a paper of ours (1) we presented a few references to Hippocrates' and
      Galen's ideas on the subject, while the main body of the article was based on the
      17th-20th centuries' relative practices. In a second paper (2), we were mainly
      testing the ancient and Medieval Greek ideas on skin catharsis against some
      clinical work of ours. In this paper we now present the ideas of the pagan and
      Byzantine Greek authors (5th cent. BC - 10th cent. AD) on the relationship of the
      human body to the natural and man-made world. Special emphasis is given to the
      relationship between purification through the skin and world purification. Based
      on the similarity of the Empedokles' concept of the four elements and
      Hippocrates' thesis concerning the four humours, the Earth itself was personified
      and became a living organism that felt cold, perspired and became dry. Man
      started to seek a natural explanation for his diseases and alterations of his
      body functions. Hence, perspiration, fever, urination, headache, stroke, were
      explained in cosmological terms. Extracts from many medical and non-medical
      writers, like Empedocles, Hippocrates, Aristotle, Galen, the Fathers of the
      Church, Meletius latrosophista, Theophilus Protospatharius, Michael Psellus and
      other sources are presented, in order to show the close relationship between an
      abundance of diseases and an array of natural phenomena.

PMID- 11962508
TI  - New cytotoxic analogues of annonaceous acetogenins.
AB  - A series of new acetogenin analogues incorporating a central catechol moiety
      instead of the tetrahydrofuran ring(s) have been prepared and tested against
      L1210 leukemia cells. Although less potent than bullatacinone, which has the same
      terminal lactone, these compounds display interesting cell cycle effects.

PMID- 11962510
TI  - Identification of a novel steroid derivative, NSC12983, as a paclitaxel-like
      tubulin assembly promoter by 3-D virtual screening.
AB  - By flexibly docking 9593 compounds of the NCI-3D database against the refined
      structure of beta-tubulin using DOCK 4.0, a long-forgotten synthetic steroid
      derivative, NSC12983, has been identified as a microtubule-stabilizing agent. The
      32 top scorers includes NSC12983 and the three added references: paclitaxel,
      docetaxel and IDN5109. That is, 12.5% of the 0.33% top scorers are active. In
      addition, NSC12983 is active on Mycobacterium tuberculosis in vitro and in vivo,
      which might be due to its ability to promote the assembly of essential cell
      division protein.

PMID- 11962509
TI  - Investigations on the biological properties of the lipophilic DHFR-inhibitory
      benzoprims reveal non-folate modes of action and opportunities for anti-cancer
      drug design.
AB  - Dichlorobenzoprim and methylbenzoprim were the lead compounds to emerge from
      investigations on a series of lipophilic 2,4-diamino-5-aryl-6-ethylpyrimidines
      synthesized and evaluated for their inhibition of dihydrofolate reductase (DHFR).
      Here the results of further mechanism-of-action studies are summarized. As
      expected, growth inhibitory activity of these compounds in the National Cancer
      Institute 60-cell-line screen correlated positively with DHFR enzyme inhibitory
      activity. Interestingly, two other aspects of their activity have been revealed.
      First, as evidenced by reversal experiments using hypoxanthine and thymidine, the
      two compounds, dichlorobenzoprim and methylbenzoprim, have been shown to exert an
      additional non-folate mechanism. Secondly, by exploitation of the COMPARE
      algorithm, a positive correlation has been established between the activity of
      certain members of this series and the existence of a mutation in the Ki-ras gene
      of non-small-cell lung and colon cancer cell lines. These observations have
      suggested that modification of the lead structures may offer opportunities to
      generate novel molecules without DHFR-inhibitory activity, but which may interact
      with new molecular targets for anti-cancer drug design.

PMID- 11962511
TI  - Nuclear and mitochondrial distribution of organoamidoplatinum(II) lesions in
      cisplatin-sensitive and -resistant adenocarcinoma cells.
AB  - The DNA binding pattern of the organoamidoplatinum(II) compound 1a is of
      considerable interest because of its known activity against cisplatin-resistant
      cells. The activity of 1a appears to be due at least in part to a greater
      cellular uptake than cisplatin into cisplatin-resistant cells, but little is
      known of the DNA reactions of the organoamidoplatinum(II) compounds. In this
      study the level of DNA cross-linking and total DNA lesions formed by 1 a were
      measured by gene-specific Southern hybridization cross-linking assays and by
      quantitative PCR in cisplatin-sensitive (2008) and in cisplatin-resistant 2008/R
      human adenocarcinoma cell lines. The surprising result was that the major
      difference between cisplatin and 1a was that the number of interstrand cross
      links induced by 1a were approximately 5-fold greater than that induced by
      cisplatin in the nuclear (but not mitochondrial) DNA of resistant cells, even
      though the total number of lesions were essentially the same in both sensitive
      and resistant cells. This result suggests that the extent of interstrand cross
      linking is a critical determinant of the cellular response to 1a and that the
      enhanced uptake of 1a into resistant cells results in this elevated level of
      cross-linking, leading to good activity of 1a against cisplatin-resistant cells.
      It remains unclear as to why 1a exhibits such selective damage to nuclear DNA,
      and insight into the molecular aspects of this selectivity will provide new
      opportunities for the further development of new platinum-based agents with
      activity against cisplatin-resistant cells.

PMID- 11962512
TI  - The role of ring D in the antitumour antibiotic streptonigrin: metal
      complexation, DNA binding and topoisomerase inhibition by ABC ring analogues of
      streptonigrin.
AB  - interaction of 7-amino-2-(6'-carboxy-2'-pyridyl)-6-methoxy-5,8-quinolinedione, an
      ABC ring analogue of the antitumour antibiotic streptonigrin, with zinc(II),
      oligonucleotides and DNA in the presence of zinc(II), and on the relaxation of
      DNA by topoisomerase II, has been studied. This ligand contains the key
      functional groups present in streptonigrin required for biological activity, but
      lacks the phenolic ring D which confers optical activity on streptonigrin.
      Variable temperature NMR experiments showed that in the presence of zinc(II)
      triflate, the methyl ester of the ligand forms a mixture of 1:1 and 1:2
      metal:ligand bipyridyl complexes, whose relative stabilities are temperature
      dependent. Titrations of the water-soluble ligand with zinc(II) nitrate at room
      temperature showed that the predominant species present in aqueous solution at
      physiological pH is the 1:1 bipyridyl complex. The interaction of the ligand with
      the hexanucleotides d(GCATGC)2 and d(ATGCAT)2 was studied by 1H- and 31P-NMR
      spectroscopy. In the presence of 1 equiv of zinc(II) nitrate and 1 equiv of the
      ligand, small changes in chemical shifts of the proton resonances associated with
      the purine resonances were detected consistent with a weak interaction of the
      zinc(II) complex of the ligand with the oligonucleotides, possibly via a groove
      binding mechanism. UV-VIS titrations showed a weak interaction of the ligand with
      calf thymus DNA and poly(dG-dC)2 in the presence of zinc(II) but negligible
      interaction with poly(dA-dT)2. Gel electrophoresis experiments showed that, in
      contrast to streptonigrin, the ligand did not inhibit the relaxation of plasmid
      DNA by human topoisomerase II. These results show that the interaction of the ABC
      ligand with zinc(II), oligonucleotides, DNA and topoisomerase II is different to
      streptonigrin and hence the design of biologically active ABC ring analogues of
      streptongrin that operate via different mechanisms should be possible.

PMID- 11962513
TI  - The novel cytotoxic sponge metabolite peloruside A, structurally similar to
      bryostatin-1, has unique bioactivity independent of protein kinase C.
AB  - A novel secondary sponge metabolite, peloruside A (peloruside), isolated from the
      marine sponge Mycale sp. (New Zealand), was tested for its cytotoxic effects on
      mammalian cells in culture. The macrolide structure of peloruside is similar to
      that of the protein kinase C (PKC) activator, bryostatin-1 (bryostatin), both
      containing a pyranose ring adjacent to a gemdimethyl moiety. Peloruside is a
      potent inhibitor of cell proliferation. Treatment of different mammalian cell
      lines with peloruside for 48-96 h gave IC50 values ranging from 4 to 15 nM, using
      the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium (MTT) cell
      proliferation assay. Peloruside was shown to be both cytostatic and cytotoxic by
      trypan blue dye exclusion tests. Peloruside induced apoptosis in a dose-dependent
      manner in murine (32D) and human (HL-60) myeloid cell lines, revealed by DNA
      laddering in agarose gels and flow cytometric analysis of annexin-V- and
      propidium iodide-stained cells. Treatment of HL-60 cells caused vacuolisation,
      partial substrate adherence, and the appearance of multi-lobed nuclei, suggesting
      the induction of a differentiation pathway. Vacuolisation was also observed in a
      human lung cancer cell line (H441). Opening of the pyranose ring of peloruside by
      sodium borohydride reduction increased the 48 h IC50 value by 26-fold in 32D
      cells, suggesting a similar active site to that proposed for bryostatin. However,
      unlike bryostatin, peloruside failed to bind to PKC in HL-60 cells and was unable
      to synergize with the calcium ionophore, ionomycin, or with interleukin-2, to
      activate T-lymphocytes in culture. In summary, although structurally similar to
      bryostatin, peloruside is a potent inhibitor of cell proliferation, has apoptosis
      inducing properties and has a unique mode of action independent of PKC.

PMID- 11962514
TI  - Synthesis and antitumor activity of substituted 3-(5-imidazo[2,1
      b]thiazolylmethylene)-2-indolinones.
AB  - The synthesis of 3-(5-imidazo]2,1-blthiazolylmethylene)-2-indolinones, analogs of
      compounds recently published, is described. The EIZ isomerism was studied by
      means of nuclear Overhauser effect experiments and X-ray crystallography. All the
      compounds were tested as potential antitumor agents. They were also tested as
      potential inhibitors of cyclin-dependent kinase 1 (CDK1), in order to determine
      if the antitumor activity was related to this mechanism of action. The results
      showed that under certain substitution conditions (5-methoxy group for the indole
      benzene ring and 2-methyl group for the imidazothiazole system), an interesting
      antitumor activity was found for some compounds. From the analysis of the
      antitumor data, 3-1(2,6-dimethylimidazo[2,1-bJ-thiazol-5-yl)methylenel-5-methoxy
      2-indolinone was the most active of the whole series.

PMID- 11962515
TI  - Synthesis, structure and tumour necrosis factor-alpha production-enhancing
      properties of novel adamantylamino heterocyclic derivatives.
AB  - The synthesis of several adamantylated aminoheterocycles is reported. The attack
      of the adamantyl cation formed from 1-adamantanol in refluxing trifluoroacetic
      acid or induced by microwave irradiation provides adamantylamino-derivatives of
      respective heterocycles. Adamantylated heterocycles enhance the induction of
      tumour necrosis factor alpha (TNF-alpha) in genetically modified murine melanoma
      cells transduced with the gene for human TNF-alpha. Of the studied collection of
      adamantylated compounds, the most biologically active are 2-adamantylamino-6
      methylpyridine and 2-adamantylamino4-methylpyrimidine. The crystal structure of 2
      adamantylamino-6-methylpyridine is reported.

PMID- 11962516
TI  - The interaction of DNA-targeted platinum phenanthridinium complexes with DNA in
      human cells.
AB  - DNA-targeted platinum phenanthridinium complexes were investigated in intact
      human cells and in tumour-bearing mice. The DNA sequence specificity of platinum
      phenanthridinium complexes was examined in intact human cells using a Taq DNA
      polymerase stop assay. It was found that the platinum phenanthridinium complexes
      had a similar sequence specificity to that of cisplatin. However, the rate at
      which DNA was damaged in intact human cells was 6-fold greater for the platinum
      phenanthridinium chloride complexes compared with cisplatin. These results are
      consistent with a DNA-targeting hypothesis where the attachment of an
      intercalating group to cisplatin places the platinum in close proximity to DNA
      and increases the rate of DNA platination. Platinum phenanthridinium iodide
      complexes were also tested, but damaged DNA at a rate similar to cisplatin. The
      platinum phenanthridinium complexes with shorter linker chain lengths damaged DNA
      more efficiently than the longer linker chain length complexes. The platinum
      phenanthridinium chloride complexes also showed significant anti-tumour activity
      in tumour-bearing (P388) mice.

PMID- 11962517
TI  - Synthesis, cytotoxicity, cell uptake and DNA interstrand cross-linking of 4,4'
      dipyrazolylmethane-linked multinuclear platinum anti-cancer complexes.
AB  - Two cationic multinuclear platinum complexes linked with the 4,4'
      dipyrazolylmethane (dpzm) ligand, trans-[[Pt(NH3)2Cl]2-mu-dpzm]Cl2 (di-Pt) and
      trans-[trans-[Pt(NH3)2Cl]2[trans-[Pt(NH3)2(mu-dpzm)2]]]Cl4 (tri-Pt), have been
      synthesized. Both complexes show activity in the murine leukaemia cell line L1210
      (IC50 = 3.8 and 2.5 microm, respectively) and the cisplatin-resistant subline
      L1210/DDP (8.8 and 3.6 microM), and in the human ovarian carcinoma 2008 (2.5 and
      17.8 microM) and its cisplatin-resistant subline C13*5 (20.9 and 37.7 microM).
      Both complexes show high levels of uptake into 2008 cells, when administered at
      100 microM, but significantly reduced uptake in the cisplatin-resistant cell line
      C13*5 (di-Pt, 66% decrease; tri-Pt, 42%; cisplatin, 86%). Both complexes form
      very high levels of DNA interstrand cross-links in vitro, with 50% interstrand
      cross-linking observed at far lower concentrations (di-Pt, 12 nM; tri-Pt, 22 nM)
      than cisplatin (450 nM). It is proposed that the higher extent of interstrand
      cross-linking may be due to the rigid nature of the dpzm linking ligand, which
      prevents the complexes from forming short-range intrastrand adducts, like the GpG
      adduct formed by cisplatin. The results of this study indicate the importance of
      the flexibility of the linking ligand for the cytotoxicity of di- and trinuclear
      platinum anti-cancer complexes.

PMID- 11962518
TI  - DNA binding properties of the indolocarbazole antitumor drug NB-506.
AB  - Indolocarbazoles derived from the antibiotic rebeccamycin represent an important
      group of antitumor agents. Several indolocarbazoles are currently undergoing
      clinical trials. These compounds inhibit topoisomerase 1 to produce DNA breaks
      that are responsible for cell death. Unlike classical topoisomerase I poisons
      like camptothecin, glycosyl indolocarbazoles can form stable complexes with DNA
      even in the absence of topoisomerase I. At least in part, their mode of action is
      reminiscent of that of the anthracyclines, which also bind to nucleic acids and
      interfere with topoisomerase II. The lead synthetic compound in the series is the
      uncharged drug NB-506, which bears a glucose residue attached to the
      indolocarbazole chromophore substituted with two hydroxyl groups at positions 1
      and 11. Here we report a detailed biophysical study aimed at characterizing the
      DNA binding properties of NB-506. Molecular modeling was used to compare the
      conformation and electronic properties of NB-506 and its analogue ED-571 bearing
      the two hydroxyl groups at positions 2 and 10. Surface plasmon resonance
      experiments, performed with DNA hairpin oligomers, indicate that NB-506 binds
      almost equally well to both AT and GC base pairs, and the binding affinity (K =
      10(5) M(-1)) is similar to that of certain classical intercalators such as
      amsacrine and bisantrene. Isothermal titration calorimetry experiments show that
      the binding of NB-506 is enthalpy-driven (deltaH = -7.2 kcal/mol). The binding
      enthalpy measured for NB-506 is similar to that obtained with doxorubicin but the
      DNA interaction processes for the two drugs differ markedly in terms of entropy
      and deltaG. The free energy of NB-506 binding to DNA is considerably less
      favorable than that of doxorubicin. These biophysical data help us to understand
      further how rebeccamycin-type anticancer drugs interact with DNA.

PMID- 11962519
TI  - [Professor Wojciech Roeske (1916-2001: honorary member of the Polish Society of
      Medical History and Pharmacy].

PMID- 11962520
TI  - [Medical recommendations of Tomasz from Wroclaw].
AB  - This article presents recommendations for physicians comprised in the last
      chapter of the fourth volume (i.e. Practica) of Michi competit, the greatest work
      by the eminent doctor Tomasz from Wroclaw, titular bishop of Sarepta, who was
      active in the 14th century in Silesia.

PMID- 11962521
TI  - [The physician and his patients: Daniel Boes (about 1662 - about 1727)].
AB  - In the present article the author presents a forgotten physician from the turn of
      XVII and XVIII centuries. Daniel Boes had been (probably) up to the year 1696 a
      physician in ordinary of King Jan III Sobieski. After the King's death he joined
      the court of Prince Karol Stanislaw Radziwill, where he performed duties of the
      physician, and from 1711 he acted as the Prince's resident in Lublin. He
      performed functions of the town councillor, and in the year 1721 - 1722 he was a
      chief officer of a group of villages in Lublin. He was an extremely popular
      physician and had a large number of patients. Among them there were also the
      highest dignitaries of the Polish Republic, arriving at the Crown Tribunal
      Sessions in Lublin.

PMID- 11962522
TI  - Commercialisation of genetic services: the role of genetic counsellors.

PMID- 11962523
TI  - Legal responses to some of the new developments in reproductive technologies,
      Part.2: the case of Diane Blood.

PMID- 11962524
TI  - Bodies, persons and research on human embryos.

PMID- 11962525
TI  - Artificial reproductive technologies (ART) applications in Turkey as viewed by
      feminists.
AB  - Since 1979, a lot of couples have benefited, in terms of having babies, from
      Artificial Reproductive Technologies (ART). In Turkey, there are presently about
      20 centres in existence for this purpose where two approved sets of regulations
      are in operation; the second being an improved form of the former. In this paper,
      ART applications in Turkey, as viewed by feminists, will be discussed. During
      ART, the body of the woman concerned is directly involved. And after every
      application, the possibility of not having a living baby can adversely affect the
      physical and psychological state of the woman in question with the trauma being
      sometimes beyond endurance. In the two sets of approved regulations mentioned
      above, this application has been questioned in terms of ethics.

PMID- 11962527
TI  - The fear of sex preselection: unwarranted or justified?

PMID- 11962526
TI  - Eye light flashes on the Mir space station.
AB  - The phenomenon of light flashes (LF) in eyes for people in space has been
      investigated onboard Mir. Data on particles hitting the eye have been collected
      with the SilEye detectors, and correlated with human observations. It is found
      that a nucleus in the radiation environment of Mir has roughly a 1% probability
      to cause an LF, whereas the proton probability is almost three orders of
      magnitude less. As a function of LET, the LF probability increases above 10
      keV/micrometer, reaching about 5% at around 50 keV/micrometer.

PMID- 11962528
TI  - Autonomy, equality and a just health care system.

PMID- 11962529
TI  - Against personal autonomy.

PMID- 11962530
TI  - Informed consent law and the forgotten duty of physician inquiry.

PMID- 11962531
TI  - Partial-birth abortion: should moral judgment prevail over medical judgment?

PMID- 11962532
TI  - Surrogacy: an Illinois policy conceived.
AB  - It is predictable that the precipitous decline in the number of available
      children for adoption will find many Illinois couples pursuing the surrogate
      route, as has happened in other states. The current uncertain status of Illinois
      law regarding surrogate contracts demands legislative focus and direction. To
      prevent protracted litigation as in other jurisdictions and to prevent injustices
      to those involved in the surrogate argument, "what we do, let us do quickly."

PMID- 11962533
TI  - Employment discrimination--Americans with Disabilities Act--Ninth Circuit holds
      that the direct threat defense is not available when an employee poses a threat
      to his own health or safety--Echazabal v. Chevron USA, Inc., 226 F.3d 1063 (9th
      Cir. 2000).

PMID- 11962534
TI  - Kimel and beyond: Fifth Circuit tackles sovereign immunity and the Family and
      Medical Leave Act in Kazmier v. Widmann.

PMID- 11962535
TI  - The effect of low molecular weight chitosan on bone resorption in vitro and in
      vivo.
AB  - We studied the effect of low molecular weight chitosan (LMWC) on the formation of
      osteoclast-like multinucleated cells (OCLs) in the co-culture of mouse
      osteoblastic cells and bone marrow cells in the presence of 1alpha,25
      dihydroxyvitamin D3 [1alpha,25(OH)2D3]. LMWC at 440 microg/ml inhibited the
      formation of tartrate-resistant acid phosphatase (TRAP)-positive OCLs induced by
      1alpha,25(OH)2D3. We prepared OCLs in the co-culture of osteoblastic cells and
      bone marrow cells. The effect of LMWC on pit formation by OCLs was examined using
      dentin slices, and LMWC inhibited pit formation at 440 microg/ml. Oral
      administration of the LMWC to ovariectomized rats prevented a decrease in bone
      mineral density (BMD) of the lumbar vertebra without affecting the body and
      uterus weights. These results suggested that LMWC prevented a decrease in BMD in
      vivo by inhibiting osteoclastic bone resorption.

PMID- 11962536
TI  - Potentiation of hypericin and hypocrellin-induced phototoxicity by omeprazole.
AB  - Hypericin and hypocrellin are potential antiviral and antineoplastic agents with
      multiple modes of light-induced biological activity connected with a production
      of singlet oxygen and/or excited-state proton transfer and consequent pH drop
      formation in the drugs environment. In present work light-induced cytotoxicity of
      hypericin (1 x 10(-5) - 10(-9) mol) and hypocrellin (1 x 10(-5) - 10(-9) mol) and
      potentiating effect of omeprazole on human leukemic cell line HL-60 was studied.
      Under dark condition cultivation none cytotoxicity was observed. The only one
      exception was hypocrellin in concentration 1 x 10(-5) mol which displayed full
      cytotoxic effect. However, illumination increased cytotoxic effect of hypericin
      and hypocrellin, both. Omeprazole, an inhibitor of H+K+-ATPase, has been used for
      testing the hypothetical pH decreasing effect of hypericin and hypocrellin in
      their cytotoxic mechanism of action. The results of our experiments have shown
      that in HL-60 cell line the effect of hypericin and hypocrellin at 1 x 10(-6) mol
      (both) was significantly potentiated by omeprazole in concentrations 1 x 10(-6) -
      10(-9) mol. Our results support the hypothesis that the excited-state proton
      transfer and the consequent acidification of hypericin and hypocrellin
      environment could play a role in the biological activity of both agents.

PMID- 11962537
TI  - Mimosa pudica may possess antidepressant actions in the rat.
AB  - In Mexico, aqueous extracts from dried leaves of Mimosa puolica are employed to
      alleviate depression. In this study, the behavioral actions of aqueous extracts
      of M. pudica at various concentrations were tested. Rats having received saline
      (0.9%; 0.30 ml; I.P.), clomipramine, desipramine or several dosages of aqueous
      extracts from M. pudica (ml = 2.0 mg/kg; m2 = 4.0 mg/kg; m3 = 6.0 mg/kg; m4 = 8.0
      mg/kg) during a 30-day period were submitted to the forced swimming test and to
      the test for differential reinforcement of low rates of response at 72 sec (DRL
      72s). Any possible anxiolytic action resulting from several doses (ml = 2.0
      mg/kg; m2 = 4.0 mg/kg; m3 = 6.0 mg/kg; m4 = 8.0 mg/kg) of extracts of M. pudica
      were compared with those caused by diazepam (1.3 mg/kg, I.P.) in the elevated
      plus-maze test. Results showed that clomipramine (1.25 mg/kg, I.P.), desipramine
      (2.14 mg/kg, I.P.) and M. pudica (6.0 mg/kg and 8.0 mg/kg, I.P.) reduced
      immobility in the forced swimming test and increased the rate of reinforcers
      received in the DRL-72s test; these data suggest that M. pudica produces
      antidepressant effects in the rat. Diazepam increased the open-arms exploration
      time in the elevated plus-maze test, but M. pudica did not show any comparable
      action at any tested dose. M. pudica therefore produced an antide-pressant-like
      profile similar to two tricyclic antidepressants.

PMID- 11962538
TI  - Prevention of psychological stress-induced immune suppression by aged garlic
      extract.
AB  - We determined the effect of Aged Garlic Extract (AGE) on damage caused to immune
      function by a psychological stress using a communication box. After four days of
      a psychological stress, a decrease in spleen weight and spleen cells was observed
      in the psychological stress-exposed mice as compared normal mice (non-stress).
      AGE significantly prevented the decreases in spleen weight and cells.
      Additionally, AGE significantly prevented the reduction of hemolytic plaque
      forming-cells in spleen cells and anti-SRBC antibody titer in serum caused by
      this psychological stress. Moreover, a reduction in NK activities was observed in
      the psychological stress-exposed mice as compared with normal mice (non-stress),
      whereas NK activities in the AGE administered mice were almost the same as normal
      mice (non-stress). These results indicate that psychological stress qualitatively
      and quantitatively impairs immune function, and that AGE is extremely useful for
      preventing psychologically-induced damage.

PMID- 11962539
TI  - Effects of the naturally-occurring chemosensitizer malagashanine and its
      combination with chloroquine on KB and P388 cell lines and isolated auricle.
AB  - Besides the determination of its LD50 value, the cytotoxicity against KB and P388
      cell lines and the toxicity on isolated guinea pig auricle of malagashanine and
      its combination with chloroquine were assessed. Malagashanine alone was devoid of
      cytotoxicity and cardiac effect on isolated auricle, and importantly, when
      combined to chloroquine, did not affect the inherent toxicity and cardiac
      toxicity of this antimalarial agent.

PMID- 11962541
TI  - Antitubercular activity of pentacyclic triterpenoids from plants of Argentina and
      Chile.
AB  - Screening of plants from South America for antitubercular activity and subsequent
      assay-guided fractionation resulted in the isolation and characterization of
      several pentacyclic triterpenoids. The MIC values of 22 triterpenoids were
      determined using the radiorespiratory BACTEC assay and range from 8 microM to
      above 128 microM. The structure-activity relationships are discussed.

PMID- 11962540
TI  - Antiviral properties of fucoidan fractions from Leathesia difformis.
AB  - Three fractions of fucoidans isolated from the brown seaweed Leathesia difformis
      (Ee, Ec and Ea) were found to be selective antiviral agents against herpes
      simplex virus (HSV) types 1 and 2 and human cytomegalovirus. Fraction Ea was the
      most active, with IC50 values in the range 0.5-1.9 microg/ml without affecting
      cell viability at concentrations up to 400 microg/ml. The antiherpetic activity
      of Ea was assessed by three different methods, plaque reduction, inhibition of
      virus yield and prevention of HSV-2 induced shut-off of cell protein synthesis,
      demonstrating that the inhibitory effect was independent of the antiviral assay
      and the multiplicity of infection. The mode of action of Ea could be ascribed to
      an inhibitory action on virus adsorption. The fucoidans did not inhibit the blood
      coagulation process even at concentrations exceeding more than 100 times the IC50
      value.

PMID- 11962542
TI  - Effect of temperature on stability of marker constituents in Echinacea purpurea
      root formulations.
AB  - Stability of an alkamide and a phenolic phytochemical marker in a hydro-alcoholic
      extract of Echinacea purpurea root and a dried powder prepared by evaporation of
      the extract was assessed in storage for 7 months at three temperature regimes: 
      20, 25 and 40 degrees Celsius. In the extract, the major alkamide, dodeca-2E, 4E,
      8Z, 10E/Z-tetraenoic acid isobutyl amide, was not significantly affected by
      storage at any of the temperatures, but cichoric acid content declined as
      significantly (P = 0.05) at both 25 degrees C and 40 degrees C as compared to low
      temperature storage. In the powder, the major alkamide showed a significantly
      reduced level at 25 degrees C and 40 degrees C while cichoric acid did not
      decline significantly. These results suggest that more attention should be given
      to the effect of formulation and temperature on storage of Echinacea products.

PMID- 11962543
TI  - Piperine mediated alterations in lipid peroxidation and cellular thiol status of
      rat intestinal mucosa and epithelial cells.
AB  - Piperine (1-Piperoyl piperidine) is the major alkaloid of black and long peppers
      used widely in various systems of traditional medicine. The present study
      investigates the toxicity of piperine via free-radical generation by determining
      the degree of lipid peroxidation and cellular thiol status in the rat intestine.
      Lipid peroxidation content, measured as thiobarbituric reactive substances
      (TBARS), was increased with piperine treatment although conjugate diene levels
      were not altered. A significant increase in glutathione levels was observed,
      whereas protein thiols and glutathione reductase activity were not altered. The
      study suggests that increased TBARS levels may not be a relevant index of
      cytotoxicity, since thiol redox was not altered, but increased synthesis
      transport of intracellular GSH pool may play an important role in cell hemostasis
      and requires further study.

PMID- 11962544
TI  - Complement-mediated antiinflammatory effect of bisbenzylisoquinoline alkaloid
      fangchinoline.
AB  - Complement-mediated mode of action of bisbenzylisoquinoline alkaloid
      fangchinoline was investigated in vivo and in vitro. The application of
      fangchinoline intraperitoneally (i.p.) to complement normal mice, strain ICR,
      inhibited the complement activity in serum and peritoneal exudate. The substance
      activated serum complement of C5-deficient DBA/2 mice. Fangchinoline was able to
      provoke local inflammatory reaction in both strains after subcutaneous (s.c.)
      injection. The alkaloid suppressed paw swelling induced by live Candida albicans
      in ICR and DBA/2 mice. Its effect depended on the dose and time of injection
      prior to inflammatory reaction. The in vitro experiments proved the interference
      of fangchinoline action with post-C5 reactions. The substance augmented C5
      convertase formation and functional activity. These results are in correspondence
      with our previous investigations, proving the complement-mediated action of
      fangchinoline. The antiinflammatory effect could be a consequence of the caused
      complement exhaustion.

PMID- 11962545
TI  - Antiulcer activity of Salvadora persica L.: structural modifications.
AB  - In previous work we observed that the decoction of Salvadora persica L. possessed
      significant protective action against ethanol and stress-induced ulcers. This
      study was designed to confirm the antiulcer activity of Salvadora persica
      decoction using optical microscopy. The elements of gastric mucosa tended to be
      reestablished normally in treated rats.

PMID- 11962546
TI  - Spasmolytic activity of some plants used by the Otomi Indians of Queretaro
      (Mexico) for the treatment of gastrointestinal disorders.
AB  - The present study was performed to investigate the effect of chloroform-methanol
      (1:1) extracts derived from Baccharis heterophylla H. B. K (Asteraceae),
      Desmodium grahami Gray (Leguminosae), Dyssodia pinnata var. pinnata Rob.
      (Asteraceae), Gentiana spathacea H. B. K. (Gentianaceae), Loeselia mexicana
      Brand. (Polemoniaceae), Selaginella pallescens Spring. (Selaginellaceae) and
      Zornia diphylla Pers. (Fabaceae) on the spontaneous contractions of isolated rat
      ileum. The concentration-response curves and IC50 values were obtained and the
      respective relaxant potencies were compared with that of the CHCl3-MeOH (1:1)
      extract of Datura lanosa. The data showed that all the extracts produce a
      concentration-dependent inhibition of spontaneous ileum contractions. In
      addition, the antimicrobial activity of the extracts against pathogenic
      enterobacteria was tested. The pharmacological actions shown by the extracts of
      the selected species tend to support ethnomedical use of the plants for the
      treatment of gastrointestinal disorders.

PMID- 11962547
TI  - Hypotensive effect of the methanolic extract of Mimusops elengi in normotensive
      rats.
AB  - The methanolic extract of Mimusops elengi caused hypotensive activity in
      anaesthetized rats. On intravenous administration (i.v.) at a dose range of 2-16
      mg/kg, it produced about a 7-38% fall in mean arterial blood pressure, in a dose
      dependent manner. The effect was independent of adrenergic, muscarinic and
      histaminergic receptors. The hypotension was also unchanged after autonomic
      ganglion or angiotensin-converting-enzyme blockade. Administration of calcium
      channel blockers, however, including nifedipine (0.9 mg/kg) and verapamil (3.9
      mg/kg), caused corresponding reductions of 81 and 64% in extract-induced
      hypotension. These data imply M. elengi might possess calcium-blocking activity
      which would explain its hypotensive effect.

PMID- 11962548
TI  - Identification of components of Prunus africana extract that inhibit lipid
      peroxidation.
AB  - Extractive and chromatographic separations were performed on V-1326, a chloroform
      extract from the bark of Prunus africana (also referred to as Pygeum africanum),
      which is used to treat the symptoms associated with benign prostate hyperplasia
      (BPH). The relative amounts of eleven identified constituents in crude V-1326 and
      in separated fractions were determined using gas chromatographic analysis. The
      ability of V-1326 and its separated fractions to inhibit ferrous ion-induced
      stimulation of lipid peroxidation in microsomal preparations from rabbit livers
      was evaluated. The extract, V-1326, and fractions containing high levels of
      myristic acid potently inhibited lipid peroxidation.

PMID- 11962549
TI  - Endoscopic management of renal lymphangioma: a case report.
AB  - A 46-year-old woman presented with total painless gross hematuria, an 8-mm
      polypoid mass that proved to be a lymphangioma was found in the upper pole
      collecting system of the left kidney. The mass was resected ureteroscopically
      with holmium laser fulguration of the base. The few reported cases of this rare
      lesion suggest that rigorous postoperative surveillance is not necessary for this
      benign condition.

PMID- 11962550
TI  - Laparoscopic vasectomy: case report and review of the literature.
AB  - A 42-year-old man undergoing bilateral laparoscopic hernia repair requested
      vasectomy for family planning purposes. Bilateral vasectomy was done by a
      laparoscopic approach at the time of extraperitoneal hernia repair, and a
      separate scrotal incision was avoided. In addition to reporting a case of
      laparoscopic vasectomy, we review the published literature on this topic.

PMID- 11962551
TI  - Laparoscopic varicocelectomy for painful varicoceles: merits and outcomes.
AB  - PURPOSE: To evaluate the effectiveness of laparoscopic ligation as an option
      offered to patients with painful varicocele. Laparoscopy has been an established
      technique for varicocelectomy in infertile patients, but little objective data
      exist addressing its effectiveness in the control of pain. PATIENTS AND METHODS:
      We reviewed records of 68 patients who underwent laparoscopic varicocelectomy for
      pain from March 1988 through March 2000. We documented patient age at operation,
      grade and side of the varicocele, duration and quality of the pain, and response
      to conservative treatment and laparoscopic ligation. RESULTS: Follow-up data were
      available for 58 patients. Their average age was 21.5 years (range 14-39 years).
      The varicocele was left sided in 51 patients and bilateral in 7. Forty patients
      described their pain as dull or throbbing ache and 13 as a dragging sensation,
      while 5 patients were unable to characterize their pain. Initial conservative
      treatment failed in all patients. Varicocele was grade III in 29 patients, grade
      II in 27, and grade I in 2. In 49 patients (84.5%), there was complete
      postoperative resolution of pain, while 6 (10.3%) had partial resolution. Only
      three patients had persistent symptoms. Hydrocele formation occurred in 3
      patients (5.2%), and varicocele persisted in 2 (3.4%). CONCLUSIONS: This
      retrospective review supports varicocele ligation for the relief of pain.
      Laparoscopic ligation is an effective and safe approach to achieve this outcome.

PMID- 11962552
TI  - Transurethral needle ablation for treatment of lower urinary tract symptoms
      associated with benign prostatic hyperplasia: outcome after 1 year.
AB  - PURPOSE: The aims of the study were to evaluate short-term effects on lower
      urinary tract symptoms and uroflowmetry and assess side effects of transurethral
      needle ablation of the prostate (TUNA). PATIENTS AND METHODS: Twenty-six men with
      a median age 68 years (range 53-77 years) were evaluated with symptom scores and
      voiding parameters before and at 3 and 12 months after TUNA. All treatments were
      performed in the outpatient department using topical anesthesia supplemented with
      sedoanalgesia. RESULTS: The International Prostate Symptom Score had decreased
      from 21.2 to 10.5 at 12 months postoperatively. Peak urinary flow was 10.9 mL/sec
      at baseline and was elevated to 13.7 mL/sec after 12 months. Residual urine
      volumes were unchanged. Postoperative urinary retention developed in 71% of the
      patients and had a mean duration of 6.3 (range 1-34) days. Postoperative perineal
      pain was noted by about half of the patients for the first 1 to 2 weeks.
      Painkillers were frequently used to reduce postoperative pain. CONCLUSIONS:
      Transurethral needle ablation is a safe procedure suitable for the outpatient
      clinic. After short-term follow-up, statistically and clinically significant
      effects were observed on symptoms and uroflow. Long-term follow-up is mandatory
      to define the future role of this therapy.

PMID- 11962553
TI  - Mediating transurethral microwave thermotherapy by intraprostatic and
      periprostatic injections of mepivacaine epinephrine: effects on treatment time,
      energy consumption, and patient comfort.
AB  - BACKGROUND AND PURPOSE: Profound intraprostatic blood flow may complicate
      reaching a therapeutic temperature in the prostate during transurethral microwave
      thermotherapy (TUMT) for benign prostatic hyperplasia (BPH). A retrospective
      survey is presented describing the effect of intraprostatic and periprostatic
      administration of mepivacaine epinephrine on treatment time, intraprostatic blood
      flow, energy delivery, and patient comfort. PATIENTS AND METHODS: Fifteen
      consecutive obstructed patients with lower urinary tract symptoms attributable to
      BPH received TUMT (ProstaLund Feedback Treatment). In order to improve patient
      comfort, injections of 10 mL of 0.5% mepivacaine epinephrine were administered in
      three locations into the prostate prior to treatment. The results were compared
      with those of a reference group consisting of 35 consecutive patients who had
      received ProstaLund Feedback Treatment without administration of mepivacaine
      epinephrine. RESULTS: Patients who received intraprostatic mepivacaine
      epinephrine had a shorter treatment time (32+/-9 minutes v 61+/-6 minutes),
      required less energy (65+/-27 kJ v 172+/-32 kJ), and had a lower calculated
      intraprostatic blood flow (13+/-5 units/minute v 26+/-12 units/minute) than the
      reference group. Patients receiving mepivacaine epinephrine also required less
      analgesic medication during the treatment. The clinical outcome in terms of
      symptom scores and peak uroflow rates appeared to be similar for the two groups.
      CONCLUSION: Intraprostatic injection of mepivacaine epinephrine prior to TUMT
      seems to have beneficial effects. It may represent an important improvement of
      thermotherapy and enable successful treatment of those patients who previously
      failed secondary to a profound intraprostatic blood flow.

PMID- 11962554
TI  - Treatment of benign prostatic hyperplasia with water-induced thermotherapy:
      experience of a single institution.
AB  - PURPOSE: To evaluate the efficacy of and tolerance for water-induced
      thermotherapy (WIT). PATIENTS AND METHODS: Between June 1998 and December 1999,
      50 patients were treated with WIT protocol. The patients were divided in two
      groups according to the achieved treatment temperature and the volume of the
      inflated treatment balloon. In Group 1, the treatment temperature was set at 60
      degrees C, and the treatment balloon was inflated to 50F. In Group II, 29
      patients were treated with a temperature of 62 degrees C, and the treatment
      balloon was inflated to a maximum of 60F. RESULTS: In Group I, the catheter was
      permanently removed in eight of the nine patients who had previously had
      permanent indwelling bladder catheters (88.8%). The average Qmax was 11.5 mL/sec;
      the quality of life (QoL) index was 1.3, and the International Prostate Symptom
      Score (IPSS) was 6.2. The remaining five patients were not catheter dependent
      prior to WIT. Three of these patients (60%) demonstrated Qmax improvements from
      11.7 to 17.1 mL/sec. In Group II, 11 of the 15 patients (73.3%) who had been
      catheter dependent resumed spontaneous micturition with a Qmax of 10.7 mL/sec and
      an IPSS of 8.5. CONCLUSION: Water-induced thermotherapy can be performed easily
      on an outpatient basis under local anesthesia. It is well tolerated by most
      patients, and the early results are encouraging.

PMID- 11962556
TI  - LiteratureWatch July-December 2001.

PMID- 11962555
TI  - Effect of hyperosmotic substances injected into the prostate of Wistar rats.
AB  - PURPOSE: To verify the effects produced by the injections of hyperosmotic
      substances into the prostate of Wistar rats as judged by gland weight, behavior,
      histologic changes, and systemic electrolytic alterations. MATERIALS AND METHODS:
      A total of 42 Wistar rats were divided into five groups and treated in the
      following manner. In Group I (N = 6), the abdominal cavity was opened and closed.
      In Group II (N = 6), a needle was introduced into the each ventral lobes of the
      prostate gland. In Group III (N = 10), a 0.9% sodium chloride solution was
      injected into the each ventral lobe of the prostate gland. In Group IV (N = 10),
      a 20% NaCl solution was injected into the each ventral lobe of the prostate
      gland. In Group V (N = 10), a 50% glucose solution was injected into the each
      ventral lobe of the prostate gland. The following parameters were studied:
      histologic features of the ventral lobes of the prostate, the electronic weight
      of the parts utilized in the surgery, and the sodium and potassium
      concentrations. RESULTS: The animals of Group V (50% glucose solution) were
      sacrificed after 60 days and showed a significant reduction in the weight of the
      ventral prostate lobes in comparison with the other groups (P = 0.05). There were
      important histologic changes in the groups which received hyperosmotic
      substances. After the 50% glucose injection, the potassium level increased
      temporarily. CONCLUSIONS: The injection of 50% glucose solution produced
      significant alterations in the tissue structure, with reduction in prostatic
      weight. The electrolyte changes were transitory.

PMID- 11962557
TI  - Transitional-cell carcinoma extending from the ureter.

PMID- 11962558
TI  - Percutaneous nephrolithotomy in the management of pediatric renal calculi.
AB  - BACKGROUND AND PURPOSES: In the era of extracorporeal shockwave lithotripsy
      (SWL), there are still some patients who will require percutaneous
      nephrolithotomy (PCNL). Our experience with this procedure is reviewed and
      discussed. PATIENTS AND METHODS: Fifty five patients with a mean age of 7.9 years
      (10 months-14 years) underwent 67 PCNL procedures on 62 renal units between
      September 1997 and April 2001. Of the patients, 13 had previous open renal
      surgery, 4 had a solitary kidney, 4 were SWL failures, 2 had osteogenesis
      imperfecta, one had anuria secondary to bilateral calculi, 2 had poorly
      functioning kidneys, and 1 had cystinuria (complete staghorn calculus). One
      disabled patient with neurologic disorders who had multiple stones underwent PCNL
      in order to decrease the stone burden and to improve the kidney function.
      Operations were performed under the guidance of monoplane fluoroscopy. Pneumatic
      or ultrasonic lithotripsy and forceps extraction were used with a rigid
      nephroscope or ureteroscope (as an alternative instrument in small-caliber
      tracts). RESULTS: Excluding the patient with neurologic disorders, 53 of the
      renal units (86.9%) were stone free at the time of discharge, and the success
      rate was 96.7%, with six patients having insignificant residual fragments after
      the procedure. In one patient, open surgery was required, and the other patient
      was sent for SWL treatment. There was no contiguous organ injury, but in 16
      procedures (23.9%), intraoperative hemorrhage was seen, and blood transfusions
      were required. CONCLUSION: Pediatric urolithiasis is usually a result of
      metabolic abnormalities and urinary tract infection, and there is always a risk
      of recurrence that may necessitate multiple additional intervention. Therefore,
      PCNL must be considered in selected cases by urologists who are experienced in
      adult percutaneous procedures.

PMID- 11962559
TI  - Laparoscopic evaluation of indeterminate renal cysts: long-term follow-up.
AB  - PURPOSE: We present our long-term follow-up of patients who have undergone
      laparoscopic evaluation for their indeterminate renal cysts, specifically
      reporting those patients who were found to have cystic renal-cell carcinoma (RCC)
      and assessing the safety and efficacy of the procedure. PATIENTS AND METHODS:
      Fifty-seven patients with indeterminate renal cysts (28 Bosniak category II and
      29 Bosniak category III) underwent laparoscopic evaluation between July 1993 and
      July 2000. A transperitoneal laparoscopic localization and aspiration of the
      cyst, cytologic analysis, and biopsy of the cyst wall and base were performed. A
      total of 11 patients were found to have cystic RCC. Patients with malignancy have
      been followed for a mean of 40 months (range 6-70 months), and five patients had
      5 years or more of follow-up. RESULTS: Eleven patients (19% of the total) were
      found to have cystic RCC. Three of these patients had Bosniak category II cysts,
      and eight had category III cysts. All tumors were low grade (I or II), and the
      stages were T1-2, Nx-0, M0. There has been no evidence of laparoscopic port site
      or renal fossa tumor recurrence, local recurrence, or metastatic disease to date
      in these patients. There is no cancer-specific mortality. CONCLUSIONS: Long-term
      follow-up indicates that laparoscopic evaluation of indeterminate renal cysts is
      not associated with an increased risk of port site or retroperitoneal or
      peritoneal recurrence of RCC. It may save a patient from undergoing open surgery
      and should be considered as a diagnostic option for patients with indeterminate
      renal cysts.

PMID- 11962561
TI  - Specimen morcellation after laparoscopic radical nephrectomy: confirmation of
      histologic diagnosis using needle biopsy.
AB  - BACKGROUND AND PURPOSE: Laparoscopic radical nephrectomy (LRN) is being
      increasingly offered for the management of renal-cell carcinoma (RCC). Specimen
      removal may be performed through a small or hand-port incision or by specimen
      morcellation. Limited studies exist addressing the accuracy of histopathologic
      diagnosis in morcellated renal tumors. Because of concerns about the lack of a
      diagnosis secondary to the morcellation process, we performed premorcellation
      needle biopsies to obtain nondisrupted tissue for pathologic analysis. Herein, we
      compare the histopathologic diagnosis achieved via needle biopsy prior to
      morcellation with that of the final specimen. PATIENTS AND METHODS: Following
      successful laparoscopic resection, specimens were entrapped in a Lapsac. Needle
      biopsies were performed manually through the mouth of the Lapsac, and
      morcellation was then done in some patients using manual and mechanical methods.
      The histopathologic diagnoses in the needle biopsy specimens and the morcellated
      material were compared. RESULTS: Laparoscopic radical nephrectomy with specimen
      morcellation was performed in 15 patients. Nine patients had premorcellation
      needle biopsies. Eight of these biopsies had sufficient tissue for diagnosis of
      RCC. This finding correlated with final diagnosis from the morcellated material.
      Perinephric fat invasion was identified in three morcellated specimens.
      CONCLUSIONS: Needle biopsy prior to specimen morcellation confirmed the
      histologic diagnosis of the morcellated specimen. This finding suggests that such
      histopathology material is adequate for diagnosis and may make premorcellation
      needle biopsy redundant.

PMID- 11962560
TI  - Radiofrequency coagulation of renal parenchyma: comparison of effects of energy
      generators on treatment efficacy.
AB  - PURPOSE: We compared experimental renal lesions created with temperature-based or
      impedance-based radiofrequency (RF) generators using normal renal parenchyma in
      an animal model with protocols recommended by the manufacturer. MATERIALS AND
      METHODS: Bilateral renal mobilization was completed in seven farm pigs in
      preparation for RF ablation, and the tines of each RF probe were expanded to a 2
      cm diameter. Pigs were sacrificed immediately (N = 3) or at 24 hours (N = 4)
      after treatment. Lesions were examined grossly and microscopically after
      hematoxylin and eosin (H&E) and nicotinamide adenine dinucleotide (NADH)
      staining. RESULTS: Gross lesions were firm and white with a hemorrhagic border,
      regardless of RF generator. Staining with H&E revealed preservation of renal
      architecture but loss of distinct cytoplasmic features with both RF systems.
      Staining for NADH showed no viable cells within the lesions produced by either RF
      system. Immediately and after a 24-hour survival, the mean sizes of the treatment
      lesions were 1.6 x 1.8 x 1.3 cm and 2.0 x 1.6 x 1.9 cm, respectively, for the
      temperature-based RF generator and 2.7 x 2.4 x 2.5 cm and 2.2 x 2.1 x 1.8 cm,
      respectively, for the impedance-based RF generator. CONCLUSION: Use of a specific
      RF energy generator with recommended treatment protocols does not appear to
      affect coagulation of normal renal parenchyma in the porcine model.

PMID- 11962562
TI  - Blind percutaneous renal access.
AB  - We describe a technique of blind percutaneous renal access when
      retrograde/intravenous imaging is not possible. We present the surgical
      technique, the patient population, and situations in which the technique is used.
      Following a review of 40 accesses, we concluded that this technique is safe,
      simple, and effective. It also allows the urologist to act autonomously in
      obtaining renal access.

PMID- 11962563
TI  - Arterioureteral fistula--a rare complication of ureterolithotomy: treatment with
      embolization.
AB  - Fistula formation between a ureteral branch of a renal artery and the ipsilateral
      ureter is rare. We describe a case that followed ureterolithotomy of an impacted
      stone. Selective angiography with embolization of the bleeding branch was
      curative.

PMID- 11962565
TI  - Violence against emergency medical services personnel.
AB  - BACKGROUND: Emergency medical services (EMS) providers may be exposed to violent
      behavior while performing their routine duties. OBJECTIVES: To determine the
      prevalence of violence against EMS providers in the prehospital setting and to
      determine factors associated with such violence. METHODS: Consecutive medical
      calls for EMS agencies in a southern California metropolitan area were
      prospectively analyzed for one month. Following each call, prehospital personnel
      recorded information about any episodes of violence (verbal or physical) during
      the run as well as variables felt to be associated with these behaviors. RESULTS:
      There were 4,102 cases available for analysis. Overall, some sort of violence
      occurred in 8.5% (349/4,102) of patient encounters. Of this reported violence,
      52.7% (184/349) was directed against prehospital care providers, while 47.3%
      (165/349) was directed against others. The prevalence of violence directed
      against prehospital care personnel was therefore 4.5% (184/4,102). Patients
      accounted for most (89.7%; 165/184) of this violent behavior. The type of
      violence varied, with 20.7% (38/184) being verbal only, 48.9% (90/184) being
      physical, and 30.4% (56/184) constituting both verbal and physical attacks. Male
      sex, patient age, and hour of the day were significantly associated with episodes
      of violence. Logistic regression analysis provided odds ratios (ORs) with
      confidence intervals (CIs) for factors that were predictive of violent behavior.
      These included police presence (OR 2.8; 95% CI 1.8-4.4), apparent presence of
      gang members (OR 2.9; 95% CI 1.6-5.3), perceived psychiatric disorder (OR 5.9;
      95% CI 3.5-9.9), and perceived presence of alcohol or drug use (OR 7.0; 95% CI
      4.4-11.2). CONCLUSION: Emergency medical services providers in some areas are at
      substantial risk for encountering violence in the prehospital setting. Certain
      situational factors may be used to predict the risk of encountering violence.
      Training, protocols, and protective gear for dealing with violent situations
      should be encouraged for all prehospital personnel.

PMID- 11962564
TI  - Use of emergency medical services for suspected acute cardiac ischemia among
      demographic and clinical patient subgroups: the REACT trial. Rapid Early Action
      for Coronary Treatment.
AB  - OBJECTIVE: Barriers to the use of emergency medical services (EMS) and patient
      delay in seeking care can limit the receipt or effectiveness of reperfusion
      therapies and the availability of prehospital emergency cardiac care. The Rapid
      Early Action for Coronary Treatment (REACT) trial was designed to determine the
      impact of a community intervention on use of EMS among demographic and clinical
      subgroups of patients with suspected acute cardiac ischemia. METHODS: A
      randomized controlled community trial was conducted in 20 pair-matched
      communities in the United States. One community from each pair received an 18
      month, multicomponent community education program. Data were collected at 44
      participating hospitals during a four-month baseline period and throughout the 18
      month trial, using medical record abstracts to collect information on mode of
      transport to the hospital and other sociodemographic and clinical variables.
      Eligible patients were persons aged > or = 30 years presenting with chest pain or
      discomfort to emergency departments (EDs) who were admitted and discharged with a
      cardiac-related diagnoses (ICD 410-414, 427-429, 440, 786.9). RESULTS: The net
      change in the odds of EMS use was an increase of 34% in intervention compared
      with control communities [adjusted odds ratio (OR) 1.34, 95% CI 1.07-1.67]. We
      observed greater increases in the odds of EMS use among patients who had chronic
      or other cardiac diagnoses (adjusted OR 1.53, 95% CI 1.18-1.99, and adjusted OR
      1.52, 95% CI 1.17-1.97, respectively) than in those diagnosed as having acute
      ischemia (adjusted OR 1.14, 95% CI 0.91-1.44). We observed greater increases in
      odds of EMS ulse in those who were retired (adjusted OR 1.62, 95% CI 1.29-2.04)
      or had systolic blood pressure (SBP) at or below 160 mm Hg upon presentation to
      the ED (adjusted OR 1.55, 95% CI 1.26-1.91 for SBP 100-160 mm Hg; 1.61, 95% CI
      0.88-2.97 for SBP <100 mm Hg). CONCLUSIONS: The REACT trial demonstrated a
      significant impact on the use of EMS among patients admitted to the hospital for
      suspected acute myocardial infarction, with greater increases among patients with
      chronic or other cardiac ICD-9 discharge diagnoses, those presenting with lower
      SBP, and retired persons.

PMID- 11962566
TI  - Utilization and impact of ambulance diversion at the community level.
AB  - OBJECTIVE: To evaluate the utilization and impact of ambulance diversion in the
      metropolitan area of Syracuse, New York. METHODS: This was a retrospective review
      of the ambulance diversion system operated by the hospitals of Syracuse, New
      York. This system allows each emergency department to divert incoming ambulances
      during periods of extreme overcrowding. Data collected included numbers of hours
      on ambulance diversion by hospital, numbers of hours when all four hospitals were
      on diversion simultaneously, and numbers of ambulances received while the
      hospitals were on and off diversion. RESULTS: For three of the five years
      evaluated, ambulance diversion hours were most numerous during the period between
      January and March. For the most recent year studied (2000), ambulance diversion
      hours did not decline after the first quarter. During periods of diversion,
      hospital emergency departments received 30%-50% fewer ambulances than they did
      while open. CONCLUSION: This study demonstrated that, in Syracuse, New York,
      ambulance diversion was once a seasonal phenomenon, but is increasingly occurring
      throughout the year because of staff and resource limitations. It also
      demonstrated that ambulance diversion can be employed to reduce numbers of
      incoming transports.

PMID- 11962567
TI  - Analysis of a medical tent at the Toronto Caribana Parade.
AB  - OBJECTIVES: To review the experience with an on-site medical tent for a mass
      gathering and to analyze patient records in a manner to more appropriately
      allocate resources and identify possible delays in definitive care. METHODS: The
      logistics of providing an on-site medical tent is reviewed, followed by a
      retrospective chart review of 126 patients over a two-year period. Prior to the
      chart review, an injury classification was developed that categorized patients
      based on the necessity of transport to hospital. Data were also analyzed for
      times of peak patient flow, types of injuries, and needless delays in definitive
      care. RESULTS: An average of 63 patients (95% CI 44-77) were seen in the tent and
      1.3 patients sought care per 10,000 spectators. Peak times were between 1600 and
      2000 hours. The average number of patients each hour was 6.5 (95% CI 0-13).
      Severe, intermediate, and minor injuries accounted for 16%, 38%, and 46% of total
      injuries, respectively. Nine cases were found where the patients arrived and left
      the medical tent by ambulance. Four of these instances may have represented a
      needless delay in definitive care. The details of each of these cases are
      reviewed. CONCLUSIONS: The results indicate that on-site medical coverage, with
      appropriate supports, is indeed safe. The frame-work provided with regard to
      setup and analysis of work-load will help others in the planning of medical care
      for similar mass gatherings.

PMID- 11962568
TI  - Injury prevention and emergency medical services: the "Accidents Aren't" program.
AB  - This report describes the rationale, purpose, structure, and content of the
      emergency medical services (EMS) injury prevention program "Accidents Aren't."
      The program is introduced with a review of injuries' toll professionally,
      epidemiologically, and economically in terms of the demand on medical care
      resources and the expense of care. With recognition that most EMS resources are
      expended on clinical care of non-critical but potentially catastrophic injuries,
      "Accidents Aren't" was designed to offer a more cost-effective means of care for
      this population and more efficient utilization of finite resources. The report
      describes the program's formulation process, its modular design, the instructor
      guidelines, the core training tool, the STARR mnemonic, and five clinical cases
      involving a wide array of injury mechanisms to which the mnemonic is applicable.
      Physician involvement in teaching and implementing the program is discussed. The
      relationship of the program to the future of EMS concludes the report.

PMID- 11962569
TI  - The evolving role of helicopter emergency medical services in the transfer of
      stroke patients to specialized centers.
AB  - BACKGROUND: In 1996, when the Food and Drug Administration (FDA) approved use of
      thrombolytic therapy for ischemic stroke, interfacility transport of stroke
      patients assumed increasing urgency. OBJECTIVE: To describe one helicopter
      emergency medical services (HEMS) program's 15-year experience with interfacility
      transport of patients with suspected stroke, with emphasis on reporting changing
      patterns seen after the advent of thrombolytic therapy for stroke. METHODS: This
      was a retrospective study of patients undergoing HEMS transport, during 1985
      1999, with a pre-transport diagnosis of suspected ischemic stroke. Data collected
      included patient demographics and times of symptom onset, community hospital
      arrival, community hospital request for HEMS, and receiving hospital arrival.
      Patients were divided into pre-thrombolysis era (1985-1995) and thrombolysis era
      (1996-1999). Group characteristics were compared using Pearson chi-square,
      Fisher's exact, rank-sum, and logistic regression analysis. RESULTS: There were
      192 total transports, 76 (40%) pre-thrombolysis era and 116 (60%) thrombolysis
      era. Thrombolysis era patients were more likely (p < 0.0001) to have time of
      symptom onset documented, and also had significantly (p = 0.0003) shorter time
      intervals between referring and receiving hospital arrival. The shorter time
      intervals were due in part to decreased time lapse between referring hospital
      arrival and that hospital's request for helicopter transport; thrombolysis era
      patients were 2.5 times more likely than pre-thrombolysis era patients to have
      HEMS activation within three hours of community hospital arrival. CONCLUSIONS:
      Helicopter EMS transport is playing an increasing role in interfacility transfer
      of patients with ischemic stroke. Earlier HEMS activation is associated with
      decreased time lapse between referral and receiving hospital arrival.

PMID- 11962570
TI  - Midazolam for the treatment of out-of-hospital pediatric seizures.
AB  - OBJECTIVE: To assess the effectiveness and safety of intravenous (IV) and
      intramuscular (IM) midazolam in the treatment of pediatric seizures by
      paramedics. METHODS: All cases in which paramedics treated patients under the age
      of 18 years with midazolam for seizures per county protocol were evaluated over a
      one-year period. Prehospital records were reviewed for treatment and
      reassessment, while the subgroup of patients who were transported to Children's
      Hospital were followed up for emergency department (ED) outcome. RESULTS:
      Midazolam was administered to 86 pediatric patients with ages ranging from 2
      months to 14 years for the treatment of seizures per county protocol. There were
      54 IV doses and 32 IM doses delivered. Of the 86 patients, post-intervention
      reevaluation was documented for 74 patients (86%) representing 49 IV and 25 IM
      doses. Improvement was reported for 91% (67/74) of patients. Greater success was
      reported with IV drug administration (47/49, 96%) as compared with 80% (20/25)
      with IM administration (p < 0.05). Four patients (three treated IM and one IV)
      had respiratory compromise necessitating field airway management. All four
      patients had respiratory compromise documented prior to midazolam administration.
      Forty-four patients were treated at Children's Hospital. Seven were intubated in
      the ED after having been given additional medications for seizures. None were
      intubated on arrival and none were felt to require intubation secondary to
      midazolam-induced respiratory depression. CONCLUSION: Prehospital IV midazolam is
      an effective intervention for pediatric seizures, while IM midazolam was
      associated with a 20% failure rate, with both having minimal risk of respiratory
      compromise.

PMID- 11962571
TI  - Prehospital trauma care in Tehran: potential areas for improvement.
AB  - OBJECTIVE: To evaluate the existing prehospital trauma care system in Tehran,
      Iran. METHODS: This was a cross-sectional study in which all trauma-related
      dispatches of Tehran's emergency medical services (EMS) system were evaluated
      during 18 randomly selected days from September 22,1997, to March 17,1998.
      Emergency medical technicians completed a checklist for all trauma cases, and the
      criteria for this performance evaluation were different partial time intervals in
      each dispatch and different procedures that had been done for the patients.
      RESULTS: The means of the "dispatch-beginning-to-scene-arrival interval" and
      "scene-arrival-to-scene-leaving interval" were 10 and 18 minutes, respectively
      (median: 10 minutes, range 0-55 minutes for the first; and median: 15 minutes,
      range 1-165 minutes for the second time interval). The mean of the "dispatch
      beginning-to-hospital-arrival interval" was 45 minutes (median: 42 minutes,
      range: 5-170 minutes). Among advanced life support (ALS) procedures that include
      cardiac monitoring, intratracheal intubation, intravenous fluid therapy,
      nasogastric tube insertion, defibrillation, and tracheostomy, only intravenous
      fluid therapy had been administered for the patients. The patients, however, had
      received different kinds of basic life support (BLS) that include initial
      evaluation, bleeding control, oxygen administration, splinting, suction use, and
      cardiopulmonary resuscitation. CONCLUSION: The prolonged response, scene, and
      dispatch-beginning-to-hospital-arrival intervals compared with those for a
      developed EMS system indicate one potential area for improvement. Furthermore,
      significant differences in the field of prehospital care (conducting no ALS
      procedure) showed that ambulance equipment and training of EMS personnel are two
      other potential sites for improvement.

PMID- 11962572
TI  - Prehospital triage of chest pain patients.

PMID- 11962573
TI  - Pediatric apparent life-threatening events: an underrecognized entity in
      emergency medical services.

PMID- 11962574
TI  - HIV postexposure prophylaxis in the remote prehospital environment.

PMID- 11962575
TI  - Spontaneously terminating ventricular fibrillation in the prehospital setting.

PMID- 11962576
TI  - Nontrauma helicopter emergency medical services transport: annotated review of
      selected outcomes-related literature.
AB  - While helicopter emergency medical services (HEMS) has its roots in military
      transport of wounded soldiers, rotor-wing transport is also used for a wide
      variety of nontrauma indications. Despite this common use of HEMS for noninjured
      patients, a Medline search found little systematic review of the literature
      pertinent to HEMS use for nontrauma. With HEMS utilization subject to
      appropriately increased scrutiny, those seeking to research HEMS utility in
      noninjured patients could benefit from existence of a collection of the topical
      literature. This paper aims to provide such a review, in the form of an annotated
      bibliography of Index Medicus journal studies assessing potential medical risks
      and benefits of HEMS transport for noninjured patients. The paper's goal is to
      provide a useful resource for those interested in pursuing more focused review of
      various sectors of the nontrauma HEMS literature. As such, the main objective of
      the article summaries is to provide a brief outline of study design and results;
      there is also limited editorial comment included after each summary.

PMID- 11962577
TI  - Agitated delirium and sudden death.

PMID- 11962578
TI  - Protection of human subjects in prehospital research.

PMID- 11962579
TI  - Prehospital care research--the basics.

PMID- 11962580
TI  - Implementation of research in the out-of-hospital setting.

PMID- 11962581
TI  - Essential resources for research: mentors, funding, and research tools.

PMID- 11962582
TI  - Writing for publication in biomedical journals.
AB  - Although not as significant as the dissemination of your results, the sense of
      accomplishment associated with publishing a manuscript in a medical journal is a
      welcome reward for working through the research process. Three basic strategies
      will help you produce a better manuscript. Careful consideration of a target
      audience and adherence to the journal's instructions for authors is the first.
      Secondly, the manuscript must describe a well-designed and conscientiously
      conducted study. No amount of creative writing can disguise a poorly designed
      study. Lastly, writing to inform rather than to impress, and doing so using clear
      and purposeful prose that is accurate and concise, is crucial. Adherence to these
      strategies will guide you in your work and will ultimately lead to successful
      publication.

PMID- 11962583
TI  - Conducting randomized trials in the prehospital setting.

PMID- 11962584
TI  - Conducting retrospective emergency medical services research.

PMID- 11962585
TI  - Emergency medical services outcomes research: evaluating the effectiveness of
      prehospital care.

PMID- 11962586
TI  - Cardiac arrest research methodology.

PMID- 11962587
TI  - The role of prehospital care providers in the advancement of public health.

PMID- 11962588
TI  - Prehospital trauma research methodology.

PMID- 11962590
TI  - PCR fusion-based approach to create reporter gene constructs for expression
      analysis in transgenic C. elegans.

PMID- 11962589
TI  - Statistical methods for prehospital care research.

PMID- 11962591
TI  - Partial heat denaturation step during reverse transcription and PCR screening
      yields full-length 5'-cDNAs.

PMID- 11962592
TI  - Chimeric gene construction without reference to restriction sites.

PMID- 11962593
TI  - Polyacrylamide gel polymerization with adjustable gelation rate.

PMID- 11962594
TI  - Total RNA-based target design for microarray analysis of defined tumor areas.

PMID- 11962595
TI  - SNP analysis by allele-specific extension in a micromachined filter chamber.

PMID- 11962596
TI  - Adventures on the dark side: an introduction to darkfield microscopy.

PMID- 11962597
TI  - Systematic analysis of intrinsic factors affecting differential display.
AB  - Differential display (DD) is a widely used method for identifying differentially
      expressed genes. To improve further the efficiency and reproducibility of the
      method, this report systematically examines four critical parameters of standard
      DD-PCR. Specifically, the study determined the optimal annealing temperature,
      elongation time, dNTP concentration, and arbitrary primer concentration. By using
      a thermal cycler that was capable of displaying a temperature gradient across a
      PCR plate, it was possible to determine (in a single experiment) the effect of
      different annealing temperatures. The optimal annealing temperaturefor a 13-mer
      arbitrary primer fell within a broad range of 40 degrees C-50 degrees C.
      Elongation times over a range of 30-120 s worked best. The optimal concentration
      for dNTPs was within a very broad range of 2-50 microM, with higher amounts
      allowing for greater pipetting accuracy. The most favorable concentration for the
      arbitrary primer was also within a broad range of 0.1-2.0 microM. A primer
      concentration below this range greatly reduced the efficiency of the
      amplification process. In conclusion, the experimental findings delineated the
      best possible DD conditions for a more reliable assessment of differential gene
      expression.

PMID- 11962598
TI  - Low efficiency of the Moloney murine leukemia virus reverse transcriptase during
      reverse transcription of rare t(8;21) fusion gene transcripts.
AB  - The resolving power of RT-PCR is limited by the efficiency of RNA-to-cDNA
      conversion. Methods to determine this efficiency, using a real-time PCR assay for
      quantifying AML1-MTG 8 [t(8;21)] fusion gene transcripts, are described. The
      efficiency is shown to be directly proportional to RNA template levels. The
      Moloney murine leukemia virus (MMLV) reverse transcriptase enzyme's conversion
      efficiency was calculated to be approximately 20%. The efficiency was even lower
      (6%) when target templates were rare (single molecules) in the RT reactions.
      Levels of nonspecific or background RNA present in the RT reaction reduced the
      reverse transcriptase's conversion efficiency. This background effect was
      particularly pronounced when the specific template was present in rare amounts.

PMID- 11962599
TI  - Peptidylprolyl isomerase A (PPIA) as a preferred internal control over GAPDH and
      beta-actin in quantitative RNA analyses.
AB  - A good internal control is critical in all quantitative analyses of gene
      expression. Levels of bet-actin, glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH), and peptidylprolyl isomerase A (PPIA) were analyzed in 78 samples (data
      obtained from our laboratory and from a publicly available database at
      http://www.ncbi.nlm.nih.gov/SAGE/). These libraries included cell lines and
      tissues from brain, breast, colon, kidney, ovary, pancreas, prostate, skin, and
      vascular origin. The level of PPIA mRNA is the most constant among the three
      genes. Hence, our study suggests that PPIA is a better internal control than beta
      actin or GAPDH, the two most commonly used internal controls.

PMID- 11962600
TI  - Efficient method to generate homologous recombinant baculovirus genomes in E.
      coli.
AB  - Here we describe a convenient method to generate homologous recombinant
      baculoviral genomes in E. coli. The recombination takes place with the aid of
      recombination enzymes provided by the phage lambda Red system between a bacmid (a
      baculoviral genome that can replicate in bacteria) and a linear fragment. Proof
      of concept was provided when the cathepsin gene (v-cath) of the Helicoverpa
      armigera single nucleocapsid nucleopolyhedrovirus (HaSNPV) was replaced by the
      chloramphenicol resistance gene (CmR). First, CmR was inserted between the
      flanking sequences of the HaS-NPV v-cath. Each of the flanking regions was about
      1 kb. The fragment was linearized and electroporated into bacteria containing
      both the HaSNPV bacmid and the lambda Red system. Recombinant bacmids resistant
      to chloramphenicol were selected. In comparison to the standard co
      transfection/plaque assays, this method significantly reduces the time required
      to construct baculovirus knockout mutants. It may also be useful in the
      manipulation of other large viral genomes.

PMID- 11962602
TI  - Tetracycline-dependent gene regulation: combinations of transregulators yield a
      variety of expression windows.
AB  - In addition to the originally described Tet transactivator tTA, several variants
      including transrepressors (tTRs) and reverse transactivators (rtTAs) have been
      constructed, which we employ here to establish a set of HeLa cell lines carrying
      different combinations of chromosomally integrated Tet transregulators. We first
      compare the regulatory properties of these lines using transient transfection of
      a luciferase reporter gene. Cell lines carrying rtTA-S2 or rtTA-M2 show reduced
      activity in the absence of dox and higher activation levels in its presence
      compared to an rtTA line. rtTA-M2 and its synthetic counterpart rtTA2S-M2 show
      the same regulation pattern. The replacement of the VP16 activation domain in
      rtTA-S2 or tTA by p65 leads to slightly reduced expression levels. Combination of
      an rtTA variant with the transrepressor tTR shows active repression of basal
      expression without affecting the activation level of the transiently transfected
      reporter gene. However, if the target gene is also chromosomally integrated, then
      tTR leads to a further reduction of basal expression and also of the maximal
      expression level. The results demonstrate that different regulatory windows can
      be achieved using various transregulators or combinations thereof. Thus, the most
      appropriate combination of regulators can be chosen depending on the application
      and cell line desired. We suspect that these properties would also allow the
      construction of transgenic organisms with preselected expression windows.

PMID- 11962603
TI  - Acrylamide capture of DNA-bound complexes: electrophoretic purification of
      transcription factors.
AB  - We have developed a rapid nonradioactive electrophoretic technique to analyze
      proteins within DNA-binding complexes, acrylamide capture of DNA-binding
      complexes (ACDC), using Acrydite-linked DNA-binding targets. The method is highly
      sensitive and easily adaptable to virtually any protein-DNA interaction. The
      utility of this technique is illustrated using recombinant and full-length
      androgen receptors and associated co-regulatory proteins present within nuclear
      extracts. In brief proteins were incubated with DNA-binding targets in which one
      oligonucleotide was synthesized with an Acrydite moiety at the 5' end to allow
      for covalent linkage to acrylamide. Alternatively, gene promoter regions were
      amplified with an Acrydite-modified PCR primer to analyze protein-DNA complexes.
      The DNA-binding reaction was polymerized into an acrylamide matrix within the
      well of a precast gel. Proteins complexed to the Acrydite DNA are trapped and
      purified by the electrophoretic migration of unbound proteins. Proteins captured
      in the Acrydite-DNA can be eluted and identified by Western analysis or 2-D gel
      electrophoresis. The advantages of this technique are that it is rapid,
      adaptable, sensitive, unlimited by the size of the DNA or protein complex, and
      can be used to detect tertiary interactions with co-regulatory factors and
      unidentified proteins. These features make the ACDC technique a powerful tool for
      transcription factor research.

PMID- 11962601
TI  - Evaluation of a homemade SYBR green I reaction mixture for real-time PCR
      quantification of gene expression.
AB  - Real-time PCR is an accurate method that can be used for the quantification of
      specific DNA molecules. Here we provide a protocol for SYBR Green I in real-time
      PCR applications using plastic reaction tubes. We report that SYBR Green I is
      alkali labile and once degraded inhibits the PCR. In our optimized protocol,
      diluted aliquots of SYBR Green I remain stable for at least two weeks. We also
      evaluated different cDNA synthesis protocols for the quantification of multiple
      genes from the same cDNA preparation. The best result was obtained with cDNAs
      synthesized by OmniScript reverse transcriptase from 2.5 microg total RNA using
      oligo d(T)18 primers. The cDNA reactions could be diluted 1:25, allowing the
      quantification of up to 125 different medium expressed genes of Arabidopsis.
      Extension times ranged between 20 and 40 bp/s for accurate quantification of PCR
      products up to approximately 400 bp in the Rotor-Gene 2000 system. Using our
      optimized real-time PCR protocol, the reproducibility and amplification
      efficiency was high and comparable to a commercially available SYBR Green I kit.
      Furthermore, the sensitivity allowed us to quantify 10-20 copies of mRNA and
      dsDNA. Thus, the protocol eliminates the need for expensive pre-made kits.

PMID- 11962604
TI  - Quantitative analysis of phenol oxidase activity in insect hemolymph.
AB  - We describe a simple, inexpensive, and robust protocol for the quantification of
      phenol oxidase activity in insect hemolymph. Discrete volumes of hemolymph from
      Drosophila melanogaster larvae are applied to pieces of filter paper soaked in an
      L-3, 4-dihydroxyphenylalanine (L-DOPA) solution. Phenol oxidase present in the
      samples catalyzes melanin synthesis from the L-DOPA precursor, resulting in the
      appearance of a roughly circular melanized spot on the filter paper. The filter
      paper is then scanned and analyzed with image-processing software. Each pixel in
      an image is assigned a grayscale value. The mean of the grayscale values for a
      circular region of pixels at the center of the image of each spot is used to
      compute a melanization index (MI) value, the computation is based on a comparison
      to an external standard (India ink). Numerical MI values for control and
      experimental larvae can then be pooled and subjected to statistical analysis.
      This protocol was used to evaluate phenol oxidase activity in larvae of different
      backgrounds: wild-type, lozenge, hopscotch(Tumorous-lethal) (which induces the
      formation of large melanotic tumors), and body-color mutations ebony and yellow.
      Our results demonstrate that this assay is sensitive enough for use in genetic
      screens with D. melanogaster and could conceivably be used for evaluation of MI
      from hemolymph of other insects.

PMID- 11962605
TI  - Efficient expression of exogenous genes in primary vascular cells using IRES
      based retroviral vectors.
AB  - Analysis of gene function in primary vascular cells has been particularly limited
      by low transfection efficiencies. Using internal ribosomal entry site (IRES)
      based retroviral vectors, we demonstrate efficient infection (range of 45%-95%)
      of primary human endothelial and smooth muscle cells with genes varying in size
      from 1.3 to 4.5 kb. Because IRES vectors are designed to allow the expression of
      two genes from a single mRNA, we can show excellent correlation between the
      expression of a reporter gene and an inserted gene of interest. Reporter gene
      expression allows rapid (24-48 h) and unambiguous identification of transduced
      cells. Additionally, reporter gene expression can be used to isolate
      subpopulations of cells that express distinct levels of cistron 1 genes by flow
      cytometry, and sorted cells maintain relative levels of gene expression over
      multiple passages in culture. Two examples of the usefulness of these vectors to
      characterize gene function in primary vascular cells include (i) the inhibition
      of endothelial cell inflammatory responses in a polyclonal population by the
      expression of a dominant negative inhibitor of nuclear factor-kappaB and (ii)
      monitoring the in vitro evolution of smooth muscle cells provided with a
      selective growth advantage by transduction with telomerase. Potential
      applications of retroviral expression strategies in vascular biology are also
      discussed.

PMID- 11962606
TI  - Construct conversions caused by simultaneous co-transfection: "GFP-walking".
AB  - Several GFP variants have been developedfor multicolor labeling in vivo. Here we
      report that simultaneous co-transfection of fluorescent protein chimeras can give
      false-positive results caused by the conversion of spectral properties. Under
      standard transfection conditions, approximately 8% of cells produce false
      positive results, but, depending on the conditions, up to 26% of the cells
      permanently express altered fusion proteins. This compromises the interpretation
      of the results. The conversion is independent of transfection methods or cell
      types. Our results show that the effect is based on homologous
      recombination/repair/replication process events that occur between the nucleotide
      sequences of the fluorescent proteins. Consecutive transfection or low sequence
      similarities avoided recombination. The appearance of conversion facilitates
      exchanges of spectral properties infusion proteins, the creation of libraries, or
      the assembly of DNA fusion constructs in vivo. The detailed quantification of the
      conversion rate allows the investigation of recombination/repair/replication
      processes in general.

PMID- 11962607
TI  - Differential display of protein tyrosine kinase cDNAs from human fetal and adult
      brains.
AB  - Here we describe a differential display method for surveying the expression of
      most protein tyrosine kinases and applying it to cDNAs from human fetal and adult
      brains. The method involves two selective steps for processing the mRNA. At each
      step, degenerate oligonucleotide primers derived from highly conserved regions of
      the catalytic domain of the kinases are used. In the display with BstYI and
      BsiHKI digests of the cDNA, 65% and 59% of a total of 72 and 63 bands,
      respectively, represented fragments from a total of 27 different tyrosine
      kinases. The expression levels of the kinases in the display were comparable with
      those measured by RT-PCR. This method offers a relatively specific way to display
      differentially expressed gene families in any tissue and cell type.

PMID- 11962608
TI  - Novel sulfoxides facilitate GC-rich template amplification.
AB  - Certain organic solvents, such as DMSO and betaine, have been reported to enhance
      PCR amplification, particularly for hard-to-amplify high-GC templates. As a
      result of extensive structure-activity studies between two groups of compounds-
      amides and sulfones--we have recently discovered several other potent PCR
      enhancers. Here we describe the effects of a series of different sulfoxides on GC
      rich template amplification and report several of these to be exceptionally
      effective, often outperforming DMSO. We introduce them as novel PCR enhancers. We
      identify tetramethylene sulfoxide as the most potent sulfur-oxygen compound in
      the enhancement of PCR amplification and as one of the most potent PCR enhancers
      currently known.

PMID- 11962609
TI  - Quantification of fibronectin adsorption to silicone-rubber cell culture
      substrates.
AB  - As the role of mechanical force in cellular signaling gained recognition,
      investigators designed a number of devices to deliver controlled regimens of
      mechanical force to cultured cells. One type of device uses thin silicone-rubber
      membranes to support monolayer cell adhesion and to transmit mechanical force in
      the form of biaxial strain. We have observed that cell attachment and spreading
      are impaired on these membranes compared to polystyrene, even when both are
      passively coated with identical amounts of extracellular matrix. The purpose of
      these studies was to quantify the efficiency and stability of passive matrix
      adsorption onto commercially available elastic culture substrates. A
      theoretically saturating density (1 microg/cm2) of fibronectin was added to each
      well, and the initial efficiency of adsorption to the walls and elastic membranes
      was found to be 31 +/- 2% of the protein added. Strikingly, when the protein
      adsorbed specifically to the membranes was quantified after seven days, only 10
      26 ng/cm2 fibronectin were present, revealing that most of the adsorption is to
      the sides of the wells. These results indicate that the adsorption of matrix
      proteins to silicone-rubber substrates is relatively inefficient and that
      investigators who use these systems must be aware of this fact and design their
      experiments accordingly.

PMID- 11962610
TI  - High-quality RNA and DNA from flow cytometrically sorted human epithelial cells
      and tissues.
AB  - Microarray technologies have made possible comprehensive analyses of nucleic acid
      sequence and expression. However, the technology to obtain efficiently high
      quality RNA and DNA suitable for array analysis from purified populations of
      neoplastic cells from human tissues has not been well addressed. Microdissection
      can enrich for populations of cells present in various tumor tissues, but it is
      not easily automated or performed rapidly, and there are tissues in which cells
      of interest cannot be readily isolated based on morphologic criteria alone. Here
      we describe a protocol for efficient RNA and DNA isolation from flow
      cytometrically purified whole epithelial cells from primary tissue. The aqueous
      reagent, RNAlater, which preserves RNA, allows immunolabeling and purification of
      whole epithelial cells by flow sorting without special instrument preparation to
      reduce RNase activity. We used real-time PCR to determine RNA quality afterflow
      sorting. High-quality RNA and DNA suitable for expression and genotype analysis
      can be readily obtained from flow cytometrically purified populations of
      neoplastic cells from human tissues.

PMID- 11962611
TI  - Multidimensional separations for protein/peptide analysis in the post-genomic
      era.
AB  - Proteomics is the study of all or part of the protein complement of genes in an
      organism, often involving the analysis of complex protein/peptide samples. Such
      complex samples are beyond the separation capacity of 1-D separation techniques.
      This review describes several multidimensional separations for proteins and
      peptides. First, several variants of 2-D liquid chromatography (2DLC) are
      reviewed, including coupled size exclusion-reversed phase, ion exchange-reversed
      phase, and reversed phase-reversed phase chromatography. Second, we describe
      coupled liquid chromatography and capillary electrophoresis methods. Finally, a
      multidimensional protein identification technique (MudPIT) is explained in
      detail. Each of the described techniques has a much higher separation capacity
      than 1-D methods and can potentially be automated for high-throughput
      experiments. In particular, MudPIT takes advantage of both the high separation
      capacity of 2DLC and the powerful peptide characterization ability of tandem mass
      spectrometry to analyze complex protein samples. Additional applications and
      developments of multidimensional liquid separations for proteomics are expected
      in the future.

PMID- 11962612
TI  - Hydrophobic targets for MALDI mass spectrometry.

PMID- 11962613
TI  - Application of immuno-mass spectrometry to analysis of a bacterial virulence
      factor.
AB  - Here we describe a novel antibody-based assay that combines specificity of
      antibody with precision of mass spectral analysis. The assay is carried out in
      three steps using a single antigen capture and transfer reagent. The first step
      of the assay involves antibody immobilization. The second step is antigen capture
      and washing to remove unbound proteins. The third step involves the analysis of
      the captured antigens by surface enhanced laser desorption ionization time-of
      flight mass spectrometry. The assay is facilitated by the ability of a single
      nonviable bacterial preparation expressing immunoglobulin-binding proteins that
      enable antibody immobilization, specific capture of fluid-phase antigen, and
      direct sample transfer to a protein chip for mass spectral analysis. Proof-of
      concept studies using a model Streptococcus pyogenes virulence factor, the
      secreted cysteine protease SpeB, are presented.

PMID- 11962614
TI  - Protein expression analysis using quantitative fluorescence image analysis on
      tissue microarray slides.
AB  - We have developed a tissue microarray (TMA)-based quantitative fluorescence image
      analysis (QFIA) method in which protein markers on TMA sections were labeled by
      immunofluorescence using tyramide signal amplification and a quantitative
      fluorescence detection system. Using this method, BRCA1 protein expression
      patterns were studied in the TMA sections of cell lines with known levels of
      BRCA1 expression and in a small group of human tissue samples obtained from
      sporadic epithelial ovarian cancers, their corresponding adjacent dysplastic
      fields, and distant non-tumor areas. We detected distinctive BRCA1 expression
      patterns in high-grade and low-grade sporadic epithelial ovarian cancers and
      their associated adjacent dysplastic fields. However, such patterns of expression
      could not be adequately detected by traditional immunohistochemical staining
      methods. TMA-QFIA provides a sensitive, automated, and quantitative measurement
      of protein expression on archived tissue and cell samples and will be a useful
      tool for protein-level molecular profiling analyses.

PMID- 11962615
TI  - In-process monitoring of protein purification with thin film silicon sensor
      technology.
AB  - We have developed a rapid and sensitive thin film assay for in-process monitoring
      of target protein purification. This novel biosensor method provides rapid (5
      min) visual evaluation of column purification fractions. The method can be used
      to monitor the efficiency of purification and potential loss of protein if the
      column binding capacity is exceeded. The eluted fractions containing the highest
      yield of target protein can be quickly identified, pooled, and processed. This
      convenient platform, known as the SILAS product, is a thin-film detection
      technology in which specific molecular interactions are transduced into visible
      color changes based on changes in the optical thickness of layers on a silicon
      surface. The results are interpreted without instrumentation. Proteins eluted
      from a purification column are adsorbed to the assay surface, and the ligand of
      interest (target) can be identified with specific binding reagents. Here we
      demonstrate two protein purification applications for the SILAS technology
      product: monitoring antibody elution from a Protein G column and evaluating the
      efficiency of purification of a glutathione-S-transferase (GST)-tagged
      recombinant protein through each step of the purification process.

PMID- 11962616
TI  - Minor groove binder-conjugated DNA probes for quantitative DNA detection by
      hybridization-triggered fluorescence.
AB  - Here we describe the properties of a novel class of oligonucleotide probes
      capable of sensitive hybridization-triggered fluorescence. These fluorogenic
      probes, known commercially as MGB Eclipse probes, are characterized by having a
      conjugated minor groove binder (MGB) ligand at the 5'-end and a fluorophore at
      the 3'-end. Additionally, they have an efficient quencher moiety at the 5'-end
      that is useful with a wide variety of fluorescent dyes. Fluorescence of the
      single-stranded MGB Eclipse probe is efficiently quenched by the interaction of
      the terminal dye and quencher groups when not hybridized. Upon hybridization to a
      complementary target, the MGB molecule folds into duplex and hyper-stabilizes it,
      allowing the use of shorter, more specific probe sequences. The 5'-MGB-quencher
      group also prevents nuclease digestion by Taq DNA polymerase during PCR. Because
      of the hybridization-triggered fluorescence and the excellent specificity
      imparted by the MGB, these 5'-MGB Eclipse probes have great versatility for real
      time PCR applications. The high sensitivity and specificity are illustrated using
      single nucleotide polymorphism detection, viral load determination, and gene
      expression analysis.

PMID- 11962617
TI  - AFLPs mark different genomic regions compared with RFLPs: a case study in tomato.
AB  - A set of three tomato chromosome 7 introgression lines (ILs) containing
      overlapping segments of Lycopersicon pennellii DNA was screened with a set of 10
      EcoRI-MseI and 10 PstI-MseI AFLP primer combinations. A large number of markers
      were identified that mapped to one of the four regions of chromosome 7 defined by
      the set of three ILs. Because many of the identified markers have known map
      positions in three tomato reference maps, their location on the tomato genome
      could be verified. It was demonstrated that the three chromosome 7 ILs carried a
      chromosome 10 region harbouring a cluster of six AFLP markers that had not been
      detected before using RFLPs. The causes and implications of this observation are
      discussed.

PMID- 11962618
TI  - AFLP markers and cytotaxonomic analysis reveal hybridisation in the genus
      Schoenus (Cyperaceae).
AB  - Molecular, cytological, and morphological data support the existence of a hybrid
      population between Schoenus nigricans and Schoenus ferrugineus. This population
      was found in northeastern Italy, where S. nigricans is central with respect to
      its natural range and S. ferrugineus is marginal, being most common in the Alps
      and in central and northern Europe. Molecular marker data show that the putative
      hybrid population is genetically intermediate between nearby populations of the
      parent species. Cytological evidence confirmed the hybrid nature of this
      population, as does the almost complete sterility of plants within the
      population. Although no seeds were produced by the hybrid population, some
      possibly fertile pollen grains were produced; this suggests that the possibility
      of introgression between the two species through the hybrids cannot completely be
      excluded.

PMID- 11962619
TI  - Development of STS and CAPS markers for identification of three tall larkspurs
      (Delphinium spp.).
AB  - One cleaved amplified polymorphic sequence (CAPS) and nine sequence tagged site
      (STS) markers were developed for identifying tall larkspur (Delphinium spp.)
      plants in three species based on the DNA sequence of known species-specific RAPD
      markers. Four STS markers were used for identification of Delphinium occidentale,
      three STS markers for Delphinium barbeyi, and one CAPS and two STS markers for
      Delphinium glaucum. One hundred sixty-six individual plants collected at 19
      locations in the western U.S.A. were tested using the STS and CAPS markers. Over
      95% of the D. occidentale plants contained all four D. occidentale specific STS
      markers, whereas the remaining plants contained three of the four STS markers.
      Approximately 97% of D. barbeyi plants contained all three D. barbeyi specific
      STS markers, and the rest had two of the three STS markers. A small percentage of
      D. barbeyi plants contained one D. occidentale specific STS marker. Hybrid
      populations were characterized as having more D. occidentale specific than D.
      barbeyi specific STS markers, suggesting that the three hybrid populations are
      composed not of F1 hybrid plants of the parental species but of segregating
      offspring of different generations from original hybrids. This set of STS and
      CAPS markers for larkspur species should be useful in classification of unknown
      plant materials and the identification of hybrid populations.

PMID- 11962621
TI  - C-banded karyotypes of two Silene species with heteromorphic sex chromosomes.
AB  - Mitotic metaphase chromosomes of Silene latifolia (white campion) and Silene
      dioica (red campion) were studied and no substantial differences between the
      conventional karyotypes of these two species were detected. The classification of
      chromosomes into three distinct groups proposed for S. latifolia by Ciupercescu
      and colleagues was considered and discussed. Additionally, a new small satellite
      on the shorter arm of homobrachial chromosome 5 was found. Giemsa C-banded
      chromosomes of the two analysed species show many fixed and polymorphic
      heterochromatic bands, mainly distally and centromerically located. Our C-banding
      studies provided an opportunity to better characterize the sex chromosomes and
      some autosome types, and to detect differences between the two Silene karyotypes.
      It was shown that S. latifolia possesses a larger amount of polymorphic
      heterochromatin, especially of the centromeric type. The two Silene sex
      chromosomes are easily distinguishable not only by length or DNA amount
      differences but also by their Giemsa C-banding patterns. All Y chromosomes
      invariably show only one distally located band, and no other fixed or polymorphic
      bands on this chromosome were observed in either species. The X chromosomes
      possess two terminally located fixed bands, and some S. latifolia X chromosomes
      also have an extra-centric segment of variable length. The heterochromatin amount
      and distribution revealed by our Giemsa C-banding studies provide a clue to the
      problem of sex chromosome and karyotype evolution in these two closely related
      dioecious Silene species.

PMID- 11962620
TI  - Microsatellite marker analysis of an anther-derived potato family: skewed
      segregation and gene-centromere mapping.
AB  - Segregation patterns of polymorphic simple sequence repeat (SSR) primer pairs
      were investigated in monoploid potato families derived from anther culture. A
      total of 14 primers developed from the sequences in the database, as well as from
      a genomic library of potato, was used. Distorted segregation was observed for
      seven (50%) polymorphic loci among monoploids derived from an interspecific
      hybrid. Similar distortion was observed for only one of five loci that could be
      contrasted between the two monoploid families. Segregation distortion was less
      common in the sexually derived backcross population between the interspecific
      hybrid and either of its parents. One locus could be putatively linked to a
      lethal allele because it showed distorted segregation in both monoploid families,
      a group of 70 heterozygous diploids derived from unreduced gametes through anther
      culture, and a backcross population. These diploids were used to map the
      polymorphic SSR markers with respect to the centromeres using half-tetrad
      analysis. The majority of the SSR loci mapped more than 33 cM from the
      centromere, suggesting the occurrence of a single crossover per chromosome arm.

PMID- 11962622
TI  - Vernalization-induced changes of the DNA methylation pattern in winter wheat.
AB  - Vernalization is a cold treatment that induces or accelerates flowering and
      insures that temperate-zone plants will not flower until after winter. There is
      evidence that vernalization results in DNA demethylation that induces flowering.
      Differences in DNA methylation can be determined using methylation-sensitive
      amplified fragment length polymorphisms (AFLPs). Methylation-sensitive AFLPs
      utilize restriction enzyme isoschizomers that are differentially sensitive to
      methylation, producing polymorphisms related to methylation differences as
      opposed to sequence differences. Near-isogenic lines (NILs) have been developed
      for spring vs. winter habit in wheat (Triticum aestivum) and allow for the study
      of a single vernalization locus. In this study, differences in the methylation
      pattern were determined for spring and winter NILs, as well as for unvernalized
      and vernalized individuals. Winter wheat was more highly methylated than spring
      wheat and methylation-related AFLPs were produced between winter and spring
      wheat. Changes in the methylation pattern were observed at the end of
      vernalization, one week after the end of vernalization, and four weeks after the
      end of vernalization of winter wheat. However, the most methylation differences
      were observed one week after removal of winter wheat from cold treatment. Our
      data suggest that there is not only a vernalization-induced demethylation related
      to flower induction, but there is also a more general and non-specific
      demethylation of sequences unrelated to flowering. Two methylation-related AFLPs
      induced by vernalization were shared among all of the winter NILs.

PMID- 11962623
TI  - Expressed sequence tags for the chicken genome from a normalized 10-day-old white
      leghorn whole-embryo cDNA library. 3. DNA sequence analysis of genetic variation
      in commercial chicken populations.
AB  - Single nucleotide polymorphisms (SNPs) have emerged as a major class of DNA
      markers with the advantage of permitting the development of high-density genetic
      maps adequate for quantitative trait loci (QTL) identification by linkage
      disequilibrium analysis. Here we describe results of a relatively high-depth
      survey of chicken broiler and layer populations for SNPs in targeted genomic
      regions of chicken expressed sequence tag (EST) sites. The sequences scanned,
      representing the composite sequence of 12 amplified fragments for a total of 6489
      bp, were randomly distributed, occurring on six different chromosomes or linkage
      groups in the chicken genome. Although one of the genomic DNA sequences did not
      match the reference cDNA sequence, another contained an intron that separated two
      putative exons. The number of SNPs observed within each of the 12 EST-targeted
      genomic regions ranged from 0 to 10 for a total of 44 and a frequency of 0.7%.
      About 70% of the polymorphisms were shared between layer and broiler populations.
      The average heterozygosity within the populations ranged from 0.15 to 0.48, with
      the layer populations showing the higher heterozygosity. SNPs and
      oligonucleotides described will provide a resource for genetic analysis in
      commercial chicken populations. The data appear to indicate that the relative
      frequency of SNPs in the targeted regions scanned is higher than the frequency
      reported for any of the other regions scanned to date in other eukaryotic
      genomes. Additionally, the results suggest that the use of DNA pools may offer an
      efficient approach to SNP detection in chickens, as has been shown in other
      vertebrates.

PMID- 11962624
TI  - Efficiency of three PCR-based markers in assessing genetic variation among cowpea
      (Vigna unguiculata subsp. unguiculata) landraces.
AB  - The main objective of this study was to investigate the efficiency of RAPD, AFLP,
      and SAMPL marker systems in detecting genetic polymorphism in cowpea landraces
      (Vigna unguiculata subsp. unguiculata (L.) Walp.) that probably share a similar
      genetic pool. A second objective was to determine the level of diversity among
      landraces from a restricted area, to define the most appropriate strategy of on
      farm conservation. Each marker system was able to discriminate among the
      materials analysed, but a clear distinction between all the local varieties was
      only obtained with AFLP and SAMPL markers. The average diversity index was quite
      similar for each marker system, but owing to the differences in the effective
      multiplex ratio values the marker index was higher for the AFLP and SAMPL systems
      than for the RAPD system. The AFLP and SAMPL techniques appear to be more useful
      than the RAPD technique in the analysis of limited genetic diversity among the
      cowpea landraces tested. The significant correlations of SAMPL similarity and
      cophenetic matrices with those of the other markers, and the lower number of
      primer combinations required, indicate that this technique is the most valuable.
      The low genetic similarity detected among landraces suggests that all the cowpea
      landraces should be maintained on the respective farms from which they came.

PMID- 11962625
TI  - cDNA sequence of five mouse guanine deaminase (Gda) alleles and mapping to mouse
      chromosome 19.
AB  - Guanine deaminase catalyses the conversion of guanine to xanthine and ammonia,
      thereby irreversibly removing the guanine base from the pool of guanine
      containing metabolites. We have identified five alleles at the mouse guanine
      deaminase locus by cDNA sequencing. These alleles were defined by single
      nucleotide polymorphisms at a total of 19 positions. For each allele the
      representative strains are as follows: Gda(a), C57BL/6J and DBA/2J; Gda(b), A/J;
      Gda(c), MOLF/Ei; Gda(d), CAST/Ei; and Gda(e), SPRET-1. The only codon change
      resulting in an amino acid substitution was found at nucleotide 523, where GAT
      was replaced by AAT in Mus spretus resulting in the deduced substitution of Asp
      174 by Asn. The single-nucleotide difference between the a and b alleles was also
      typed by allele-specific oligonucleotide amplification for 17 common strains of
      Mus musculus susbp. musculus. By typing the AxB and BxA recombinant inbred (RI)
      strain sets, Gda was mapped to mouse chromosome 19, a region syntenic with human
      chromosome 9q11-q22.

PMID- 11962626
TI  - An enhanced molecular marker based genetic map of perennial ryegrass (Lolium
      perenne) reveals comparative relationships with other Poaceae genomes.
AB  - A molecular-marker linkage map has been constructed for perennial ryegrass
      (Lolium perenne L.) using a one-way pseudo-testcross population based on the
      mating of a multiple heterozygous individual with a doubled haploid genotype.
      RFLP, AFLP, isoenzyme, and EST data from four collaborating laboratories within
      the International Lolium Genome Initiative were combined to produce an integrated
      genetic map containing 240 loci covering 811 cM on seven linkage groups. The map
      contained 124 codominant markers, of which 109 were heterologous anchor RFLP
      probes from wheat, barley, oat, and rice, allowing comparative relationships
      between perennial ryegrass and other Poaceae species to be inferred. The genetic
      maps of perennial ryegrass and the Triticeae cereals are highly conserved in
      terms of synteny and colinearity. This observation was supported by the general
      agreement of the syntenic relationships between perennial ryegrass, oat, and rice
      and those between the Triticeae and these species. A lower level of synteny and
      colinearity was observed between perennial ryegrass and oat compared with the
      Triticeae, despite the closer taxonomic affinity between these species. It is
      proposed that the linkage groups of perennial ryegrass be numbered in accordance
      with these syntenic relationships, to correspond to the homoeologous groups of
      the Triticeae cereals.

PMID- 11962627
TI  - Enhancer of garnet/deltaAP-3 is a cryptic allele of the white gene and identifies
      the intracellular transport system for the white protein.
AB  - The white gene encodes an ABC-type transmembrane transporter that has a role in
      normal eye pigment deposition. In addition, overexpression in Drosophila leads to
      homosexual male courtship. Its human homologue has been implicated in cholesterol
      transport in macrophages and in mood disorders in human males. The garnet gene is
      a member of a group of other Drosophila eye colour genes that have been shown, or
      proposed, to function in intracellular protein transport. Recent molecular
      analysis indicates that it encodes the delta subunit of the AP-3 adaptin complex
      involved in vesicle transport from the trans-Golgi network to lysosomes and
      related organelles, such as pigment granules. This identification revealed a
      novel role for intracellular vesicular transport in Drosophila pigmentation. To
      further analyze this intracellular transport system, we examined the genetic
      interactions between garnet and a second site enhancer mutation, enhancer of
      garnet (e(g)). We show here that e(g) is a cryptic allele of the white gene. The
      white-garnet interaction is highly sensitive to the levels of both gene products
      but also shows some allele specificity for the white gene. The additive effect on
      pigmentation and the predicted protein products of these genes suggest that the
      garnet/AP-3 transport system ensures the correct intracellular localization of
      the white gene product. This model is further supported by the observation of
      homosexual male courtship behavior in garnet mutants, similar to that seen in
      flies overexpressing, and presumably mis-sorting, the white gene product. The
      w(e(g)) allele also enhances mutations in the subset of other eye-color genes
      with phenotypes similar to garnet. This observation supports a role for these
      genes in intracellular transport and leads to a model whereby incorrect sorting
      of the white gene product can explain the pigmentation phenotypes of an entire
      group of eye-color genes.

PMID- 11962628
TI  - A molecular phylogenetic study of two relict species of melanopline grasshoppers.
AB  - Two species belonging to the large grasshopper genus Melanoplus, Melanoplus
      gaspesiensis and Melanoplus madeleineae, are thought to have survived in refugia
      in eastern Canada during the Wisconsin glaciation period and perhaps during
      earlier glacial episodes as well. It has been proposed that either Melanoplus
      borealis, which is widely distributed today, or its antecedent gave rise to the
      two relict species. Our research, based on standard phylogenetic analyses of
      mitochondrial sequences, examines this claim by establishing the positions of M.
      gaspesiensis and M. madeleineae within Melanoplus. There is a very close and
      strongly supported connection between M. madeleineae and M. borealis (d = 1.36%),
      whereas M. gaspesiensis is more distant from the latter (d = 2.08%) and appears
      closely aligned with two other species. Molecular clock estimates of the times of
      separation of M. madeleineae and M. gaspesiensis from M. borealis are 0.68 and
      1.04 million years ago, respectively. Within-species diversities of 1.01 and
      0.70% for M. madeleineae and M. gaspesiensis, respectively, are of comparable
      magnitudes to that of the continentally distributed Melanoplus sanguinipes
      (0.86%), clearly indicating that neither species endured bottleneck effects
      despite isolation.

PMID- 11962629
TI  - High-throughput targeted SSR marker development in peach (Prunus persica).
AB  - Simple sequence repeats (SSRs) have proven to be highly polymorphic, easily
      reproducible, codominant markers. However, developing an SSR map is very time
      consuming and expensive, and most SSRs are not specifically linked to gene loci
      of immediate interest. The ideal situation would be to combine a high-throughput,
      relatively inexpensive mapping technique with rapid identification of SSR loci in
      mapped regions of interest. For this reason, we coupled the high-throughput
      technique of AFLP mapping with subsequent direct targeting of SSRs identified in
      AFLP-marked regions of interest. This approach relied on the availability of
      peach bacterial artificial chromosome (BAC) library resources. We present
      examples of using this strategy to rapidly identify SSR loci tightly linked to
      two important, simply inherited traits in peach (Prunus persica (L.) Batsch):
      root-knot nematode resistance and control of the evergrowing trait. SSRs
      developed in this study were also tested for their transportability in other
      Prunus species and in apricots.

PMID- 11962630
TI  - A compilation of soybean ESTs: generation and analysis.
AB  - Whole-genome sequencing is fundamental to understanding the genetic composition
      of an organism. Given the size and complexity of the soybean genome, an
      alternative approach is targeted random-gene sequencing, which provides an
      immediate and productive method of gene discovery. In this study, more than
      120000 soybean expressed sequence tags (ESTs) generated from more than 50 cDNA
      libraries were evaluated. These ESTs coalesced into 16928 contigs and 17336
      singletons. On average, each contig was composed of 6 ESTs and spanned 788 bases.
      The average sequence length submitted to dbEST was 414 bases. Using only those
      libraries generating more than 800 ESTs each and only those contigs with 10 or
      more ESTs each, correlated patterns of gene expression among libraries and genes
      were discerned. Two-dimensional qualitative representations of contig and library
      similarities were generated based on expression profiles. Genes with similar
      expression patterns and, potentially, similar functions were identified. These
      studies provide a rich source of publicly available gene sequences as well as
      valuable insight into the structure, function, and evolution of a model crop
      legume genome.

PMID- 11962631
TI  - Species relationships between antifungal chitinase and nuclear rDNA (internal
      transcribed spacer) sequences in the genus Hordeum.
AB  - The sequences of the chitinase gene (Chi-26) and the internal transcribed spacer
      of 18S - 5.8S - 26S rDNA (ITS1) were determined to analyze the phylogenetic
      relationships among species representing the four basic genomes of the genus
      Hordeum. Grouping analysis based on data for Chi-26 gene sequences placed Hordeum
      secalinum (H genome) near the Hordeum murinum complex (Xu genome), and Hordeum
      bulbosum distant from the other species that carried the I genome. ITS sequence
      data showed the expected grouping based on the genome classification of the
      species studied. Different sequences of ITS were detected even in the genomes of
      the diploid species. The results are interpreted in terms of defective or
      unfinished concerted evolution processes in each taxon.

PMID- 11962632
TI  - Tissue-specific expression of male-transmitted mitochondrial DNA and its
      implications for rates of molecular evolution in Mytilus mussels (Bivalvia:
      Mytilidae).
AB  - Mytilus and other bivalves exhibit an unusual system of mitochondrial DNA (mtDNA)
      transmission termed doubly uniparental inheritance (DUI). Specifically, males
      transmit the mtDNA they have received from their fathers to their sons. Females
      transmit their mother's mtDNA to both sons and daughters. Males are normally
      heteroplasmic and females are normally homoplasmic, but not exclusively. This
      system is associated with an unusual pattern of molecular evolution. Male
      transmitted mtDNA (M type) evolves faster than female-transmitted (F type) mtDNA.
      Relatively relaxed selection on the M type has been proposed as an explanation
      for this phenomenon. To further evaluate the selective forces acting upon the M
      type genome, we used RT-PCR to determine where it is expressed. M-type mtDNA
      expression was detected in all gonad samples and in 50% of somatic tissues of
      males, and in a single female tissue. F-type mtDNA expression was detected in all
      female tissues, all male somatic tissues, and all but one male gonad sample. We
      argue that the expression of M-type mtDNA in male somatic and male gonad tissues
      has implications for the strength of selection acting upon it.

PMID- 11962633
TI  - Assessing the level of collinearity between Arabidopsis thaliana and Brassica
      napus for A. thaliana chromosome 5.
AB  - This study describes a comprehensive comparison of chromosome 5 of the model
      crucifer Arabidopsis with the genome of its amphidiploid crop relative Brassica
      napus and introduces the use of in silico sequence homology to identify conserved
      loci between the two species. A region of chromosome 5, spanning 8 Mb, was found
      in six highly conserved copies in the B. napus genome. A single inversion
      appeared to be the predominant rearrangement that had separated the two lineages
      leading to the formation of Arabidopsis chromosome 5 and its homologues in B.
      napus. The observed results could be explained by the fusion of three ancestral
      genomes with strong similarities to modern-day Arabidopsis to generate the
      constituent diploid genomes of B. napus. This supports the hypothesis that the
      diploid Brassica genomes evolved from a common hexaploid ancestor. Alignment of
      the genetic linkage map of B. napus with the genomic sequence of Arabidopsis
      indicated that for specific regions a genetic distance of 1 cM in B. napus was
      equivalent to 285 Kb of Arabidopsis DNA sequence. This analysis strongly supports
      the application of Arabidopsis as a tool in marker development, map-based gene
      cloning, and candidate gene identification for the larger genomes of Brassica
      crop species.

PMID- 11962634
TI  - Comparison of orthologous and paralogous DNA flanking the wheat high molecular
      weight glutenin genes: sequence conservation and divergence, transposon
      distribution, and matrix-attachment regions.
AB  - Extended flanking DNA sequences were characterized for five members of the wheat
      high molecular weight (HMW) glutenin gene family to understand more of the
      structure, control, and evolution of these genes. Analysis revealed more sequence
      conservation among orthologous regions than between paralogous regions, with
      differences mainly owing to transposition events involving putative
      retrotransposons and several miniature inverted transposable elements (MITEs).
      Both gyspy-like long terminal repeat (LTR) and non-LTR retrotransposon sequences
      are represented in the flanking DNAs. One of the MITEs is a novel class, but
      another MITE is related to the maize Stowaway family and is widely represented in
      Triticeae express sequence tags (ESTs). Flanking DNA of the longest sequence, a
      20 425-bp fragment including and surrounding the HMW-glutenin Bx7 gene, showed
      additional cereal gene-like sequences both immediately 5' and 3' to the HMW
      glutenin coding region. The transcriptional activities of sequences related to
      these flanking putative genes and the retrotransposon-related regions were
      indicated by matches to wheat and other Triticeae ESTs. Predictive analysis of
      matrix-attachment regions (MARs) of the HMW glutenin and several alpha-, gamma-,
      and omega-gliadin flanking DNAs indicate potential MARs immediately flanking each
      of the genes. Matrix binding activity in the predicted regions was confirmed for
      two of the HMW-glutenin genes.

PMID- 11962635
TI  - Molecular characterization of a 2.7-kb, 12q13-specific, retroviral-related
      sequence isolated by RDA from monozygotic twin pairs discordant for
      schizophrenia.
AB  - This report deals with the molecular characterization of a representational
      difference analysis (RDA)-derived sequence (SZRV-2, GenBank accession No.
      AF135486; Genome Database accession Nos. 7692183 and 7501402) from three
      monozygotic twin pairs discordant for schizophrenia (MZD). The results suggest
      that it is a primate-specific, heavily methylated, and placentally expressed (-7
      kb mRNA) endogenous retroviral-related (ERV) sequence of the human genome. We
      have mapped this sequence to 12q13 using two SZRV-2 positive BAC clones (4K11
      (Genome Survey Sequence Database No. 1752076; GenBank accession No. AZ301773) and
      501H16) by fluorescence in situ hybridization. End sequencing of the 4K11 BAC
      clone has allowed identification of nearby genes from the human genome database
      at NCBI that may be of interest in schizophrenia research. These include viral
      related sequences (potential hot spots for insertions), developmental, channel,
      and signal transduction genes, as well as genes affecting expression of certain
      receptors in neurons. Furthermore, when used as a probe on Southern blots, SZRV-2
      detected no difference between schizophrenia patients from southwestern Ontario
      and their matched controls. However, it identified aberrant methylation in one of
      the eight patients and none of the 21 unaffected controls. Although additional
      experiments will be required to establish the significance, if any, of SZRV-2
      methylation in the complex etiology of schizophrenia, molecular results included
      offer a novel insight into the role of retroviral-related sequences in the
      origin, organization, and regulation of the human genome.

PMID- 11962636
TI  - Repetitive DNas of wild emmer wheat (Triticum dicoccoides) and their relation to
      S-genome species: molecular cytogenetic analysis.
AB  - We have analyzed the chromosomal GISH molecular banding patterns of three
      populations of the wild allopolyploid wheat Triticum dicoccoides in an attempt to
      unravel the evolutionary relationships between highly repetitive DNA fractions of
      T. dicoccoides and proposed diploid progenitors of the B genome. Aegilops
      speltoides showed almost complete affinity of its repetitive DNA to C
      heterochromatin of T. dicoccoides, whereas other S-genome species demonstrated
      relatedness only to distal heterochromatin. This substantiates the priority of
      Ae. speltoides as the most similar to the wheat B-genome donor in comparison with
      other Sitopsis species. Using molecular banding technique with DNA of different
      Aegilops species as a probe permits tracing of the origin of each heterochromatin
      cluster. Molecular banding analysis reveals polymorphism between three wild emmer
      wheat populations. Comparison of molecular banding patterns with chromosomal
      distribution of the Ty1-copia retrotransposons, which constitute a large share of
      T. dicoccoides genome, makes it possible to propose that the activity of
      transposable elements may lie in the background of observed intraspecific
      polymorphism.

PMID- 11962637
TI  - Integrated karyotyping of sorghum by in situ hybridization of landed BACs.
AB  - The reliability of genome analysis and proficiency of genetic manipulation are
      increased by assignment of linkage groups to specific chromosomes, placement of
      centromeres, and orientation with respect to telomeres. We have endeavored to
      establish means to enable these steps in sorghum (Sorghum bicolor (L.) Moench),
      the genome of which contains ca. 780 Mbp spread across n = 10 chromosomes. Our
      approach relies on fluorescence in situ hybridization (FISH) and integrated
      structural genomic resources, including large-insert genomic clones in bacterial
      artificial chromosome (BAC) libraries. To develop robust FISH probes, we selected
      sorghum BACs by association with molecular markers that map near the ends of
      linkage groups, in regions inferred to be high in recombination. Overall, we
      selected 22 BACs that encompass the 10 linkage groups. As a prelude to
      development of a multiprobe FISH cocktail, we evaluated BAC-derived probes
      individually and in small groups. Biotin- and digoxygenin-labeled probes were
      made directly from the BAC clones and hybridized in situ to chromosomes without
      using suppressive unlabelled C0t-1 DNA. Based on FISH-signal strength and the
      relative degree of background signal, we judged 19 BAC-derived probes to be
      satisfactory. Based on their relative position, and collective association with
      all 10 linkage groups, we chose 17 of the 19 BACs to develop a 17-locus probe
      cocktail for dual-color detection. FISH of the cocktail allowed simultaneous
      identification of all 10 chromosomes. The results indicate that linkage and
      physical maps of sorghum allow facile selection of BAC clones according to
      position and FISH-signal quality. This capability will enable development of a
      high-quality molecular cytogenetic map and an integrated genomics system for
      sorghum, without need of chromosome flow sorting or microdissection. Moreover,
      transgeneric FISH experiments suggest that the sorghum system might be applicable
      to other Gramineae.

PMID- 11962638
TI  - RAPD isolation of a Y chromosome specific ORF in a dioecious plant, Silene
      latifolia.
AB  - Silene latifolia is a dioecious plant and has heteromorphic sex chromosomes: the
      X and Y chromosomes. The Y chromosome is the largest, and its genetic control
      seems to be most strict among dioecious plants. To identify the putative sex
      determination elements on the Y chromosome, random amplified polymorphic DNA
      (RAPD) analysis was used to screen for Y chromosome specific DNA fragments, and
      31 clones were successfully produced. Genomic Southern hybridization and FISH
      (fluorescence in situ hybridization) analyses revealed that one of the clones, #2
      2, is a Y chromosome specific fragment that has a single copy on the Y
      chromosome. Sequence tagged site (STS)-PCR analysis also succeeded in amplifying
      one fragment in males and no fragments in females. Cloning and sequencing of the
      #2-2 flanking region using inverse PCR revealed an open reading frame (ORF)
      corresponding to 285 amino acids in length (ORF285), but no expression of the
      ORF285 gene was identified. ORF285 may be a clue to the origin of dioecy.

PMID- 11962639
TI  - Identification of highly transformable wheat genotypes for mass production of
      fertile transgenic plants.
AB  - The efficiency of wheat biolistic transformation systems strongly depends on the
      bombardment parameters, the condition of the donor plant, and the plant genotype
      chosen for the transformation process. This paper analyzes the transformation
      efficiency of the 129 wheat sister lines generically called 'Bobwhite',
      originally obtained from the cross 'Aurora'//'Kalyan'/'Bluebird 3'/'Woodpecker'.
      A number of factors influencing the transformation were examined, such as the
      ability to produce embryogenic callus, regeneration in selection medium, and
      overall transformation performance. Of the 129 genotypes evaluated, eight
      demonstrated transformation efficiencies above 60% (60 independent transgenic
      events per 100 immature embryos bombarded). Among the eight genotypes identified,
      we studied agronomic characteristics such as earliness to identify the most
      adaptable line(s) for different lab conditions. 'Bobwhite' SH 98 26 was
      identified as a super-transformable wheat line.

PMID- 11962640
TI  - Isolation of A/D and C genome specific dispersed and clustered repetitive DNA
      sequences from Avena sativa.
AB  - DNA gel-blot and in situ hybridization with genome-specific repeated sequences
      have proven to be valuable tools in analyzing genome structure and relationships
      in species with complex allopolyploid genomes such as hexaploid oat (Avena sativa
      L., 2n = 6x = 42; AACCDD genome). In this report, we describe a systematic
      approach for isolating genome-, chromosome-, and region-specific repeated and low
      copy DNA sequences from oat that can presumably be applied to any complex genome
      species. Genome-specific DNA sequences were first identified in a random set of
      A. sativa genomic DNA cosmid clones by gel-blot hybridization using labeled
      genomic DNA from different Avena species. Because no repetitive sequences were
      identified that could distinguish between the A and D gneomes, sequences specific
      to these two genomes are refereed to as A/D genome specific. A/D or C genome
      specific DNA subfragments were used as screening probes to identify additional
      genome-specific cosmid clones in the A. sativa genomic library. We identified
      clustered and dispersed repetitive DNA elements for the A/D and C genomes that
      could be used as cytogenetic markers for discrimination of the various oat
      chromosomes. Some analyzed cosmids appeared to be composed entirely of genome
      specific elements, whereas others represented regions with genome- and non
      specific repeated sequences with interspersed low-copy DNA sequences. Thus,
      genome-specific hybridization analysis of restriction digests of random and
      selected A. sativa cosmids also provides insight into the sequence organization
      of the oat genome.

PMID- 11962641
TI  - Identification of mitotic chromosomes of tuberous and non-tuberous solanum
      species (Solanum tuberosum and Solanum brevidens) by GISH in their interspecific
      hybrids.
AB  - GISH (genomic in situ hybridization) was applied for the analysis of mitotic
      chromosome constitutions of somatic hybrids and their derivatives between
      dihaploid clones of cultivated potato (Solanum tuberosum L.) (2n = 2x = 24, AA
      genome) and the diploid, non-tuberous, wild species Solanum brevidens Phil. (2n =
      2x = 24, EE genome). Of the primary somatic hybrids, both tetraploid (2n = 4x)
      and hexaploid (2n = 6x) plants were found with the genomic constitutions of AAEE
      and AAEEEE, respectively. Androgenic haploids (somatohaploids) derived from the
      tetraploid somatic hybrids had the genomic constitutions of AE (2n = 2x = 24) and
      haploids originating from the hexaploid hybrids were triploid AEE (2n = 3x = 33
      and 2n = 3x = 36). As a result of subsequent somatic hybridization from a fusion
      between dihaploid S. tuberosum (2n = 2x = 24, genome AA) and a triploid
      somatohaploid (2n = 3x = 33, genome AEE), second-generation somatic hybrids were
      obtained. These somatic hybrids were pentaploids (2n = 5x, genome AAAEE), but had
      variable chromosome numbers. GISH analysis revealed that both primary and second
      generation somatic hybrids had lost more chromosomes of S. brevidens than of S.
      tuberosum.

PMID- 11962642
TI  - NMDA and strychnine diversely modulate spinal dorsal horn noxious responsiveness
      in normal rats: potential significance to sensory disorders in neuropathic pain.
AB  - Changes in neuronal excitability due to increase in excitatory transmitters
      and/or removal of local inhibition underlie central neuron sensitization and
      altered responsiveness related to painful sensory disorders. To distinguish the
      contribution of each of the two mechanisms, they have been mimicked separately in
      intact rats, by iontophoretically applying excitatory (NMDA) and disinhibitory
      (the glycine antagonist strychnine) substances during dorsal horn neuron
      recording. Wide dynamic range (WDR) neurons were extracellularly recorded at the
      L5-L6 lumbar level in anesthetized and paralyzed rats and an analysis was made,
      before and during the substance application, of the characteristics of the
      response to noxious stimuli applied to areas supplied by the ipsilateral sciatic
      nerve and the contralateral sciatic and saphenous nerves ("inappropriate" areas).
      The results show that the neuronal response properties were modified differently
      during the NMDA-induced hyperexcitability and strychnine-induced release of
      inhibition. Both manipulations brought about the unmasking of responses to
      previously ineffective, noxious stimuli applied to the contralateral sciatic and
      saphenous nerve areas, and the enhancement of the responses to noxious
      stimulation of the ipsilateral sciatic nerve area. However, it was only during
      the increased excitation induced by NMDA that the neurons exhibited
      hyperresponsiveness, with long-lasting afterdischarge, to noxious stimulation of
      the ipsi- and contralateral areas. Such response features resemble those
      described in sensitized neurons in neuropathic rats and associated with
      behavioral signs of hyperalgesia. This suggests, by inference, a crucial
      contribution of the NMDA-induced increased excitability to the expression of
      neuronal sensitization related to this painful sensory disorder.

PMID- 11962643
TI  - The prevalence of tactile motion aftereffects.
AB  - The present study examined the prevalence of motion aftereffects (MAEs) in the
      sense of touch. The effects of two types of apparatuses were tested: a ridged,
      spinning cylinder and an array of vibrating tactors from the Optacon, a reading
      aid for the blind. In the first phase of the study, 50 subjects were tested for a
      total of 200 trials on both stimulators. Approximately one-third of the trials
      with both stimulators produced reports of MAEs in either the negative (expected)
      direction or the positive direction relative to the adapting stimulus. With the
      cylinder stimulator, there were significantly more reports of positive MAEs than
      negative MAEs. Subjects who reported MAEs in the first phase of the experiment
      were tested again in the second phase of the experiment. This additional testing
      produced results similar to those obtained in the first phase and did not produce
      a substantial increase in the number of reports of MAEs. It appears that tactile
      MAEs are not as readily generated as visual MAEs.

PMID- 11962644
TI  - The distribution of respiration-related and swallowing-related motoneurons
      innervating the rat genioglossus muscle.
AB  - The present study was an attempt to identify the location of genioglossal
      respiratory and swallowing motoneuron cell bodies within the hypoglossal (XII)
      nucleus using both electrophysiological and morphological studies. The
      genioglossus muscle is innervated by the genioglossal branch of the medial XII
      nerve. At the entrance to the muscle, the genioglossal branch divides in the
      directions of the mandible and tongue. Five of five rats displayed both
      respiratory-related and swallowing-related bursts in the medial XII branch
      towards the mandible. All five rats also displayed swallowing-related bursts in
      the medial XII branch towards the tongue. In addition, horseradish peroxidase
      conjugated to wheatgerm agglutinin (HRP:WGA) was injected into the proximal cut
      ends of each branch. When HRP:WGA was injected into the branch in the direction
      of the mandible, HRP-labeled cells were detected in the lateral region of the
      ventromedial subnucleus in the XII nucleus, extending from 0.7 to 1.2 mm rostral
      to the obex. On the other hand, after injection into the branch in the direction
      of the mandible, HRP-labeled cells were detected in the ventromedial subnucleus
      of the XII nucleus, extending from 0.3 to 1.2 mm rostral to the obex. These
      results provide evidence that genioglossal respiration-related and swallowing
      related motoneurons are located in different portions within the ventromedial
      subnucleus of the XII nucleus.

PMID- 11962645
TI  - Organization of the ferret lateral cervical nucleus and cervicothalamic tract.
AB  - To elucidate the organization of the ferret spinocervicothalamic pathway (SCTP),
      we examined the lateral cervical nucleus (LCN) and the termination of the
      cervicothalamic tract (CTY) in this species. In thionin-stained sections, the
      ferret LCN appeared as an easily delineated column of cells in the dorsolateral
      funiculus from about mid-C3 to the rostral end of C1, with most cells located in
      the C1 and C2 segments. In transverse sections, the LCN was elongated along a
      dorsolateral to ventromedial axis and in the rostral half of C2 and caudal half
      of C1 continuous with the neck of the dorsal horn. The number of ferret LCN cells
      was estimated to 2,500-3,700, with an average of 3,340. Substance P-like
      immunoreactive fibers located preferentially in the ventromedial part of the LCN,
      whereas serotonin-like immunoreactive fibers were found throughout the nucleus.
      Anterograde transport of wheat germ agglutinin-horseradish peroxidase conjugate
      and biotinylated dextran amine demonstrated that the ferret CTT terminates
      extensively in the peripheral parts of the ventral posterior lateral nucleus.
      Sparser termination was evident in the ventral posterior inferior nucleus, in the
      medial nucleus of the posterior complex, and in the medial part of the
      magnocellular medial geniculate nucleus. Thus, although the LCN is significantly
      smaller in ferrets than in cats and raccoons, the organization of the LCN and of
      the cervicothalamic tract is closely similar in the three species. These findings
      indicate a conserved general organization of the SCTP among carnivores.

PMID- 11962646
TI  - The role of cutaneous feedback for anticipatory grip force adjustments during
      object movements and externally imposed variation of the direction of gravity.
AB  - Grip force adjustments to changes of object loading induced by external changes
      of the direction of gravity during discrete arm movements with a grasped object
      were analyzed during normal and anesthetized finger sensibility. Two subjects
      were seated upright in a rotatable chair and rotated backwards into a horizontal
      position during discrete movements with a hand-held instrumented object. The
      movement direction varied from vertical to horizontal inducing corresponding
      changes in the direction of gravity, but the orientation of the movement in
      relation to the body remained unaffected. During discrete vertical movements a
      maximum of load force occurs early in upward and late in downward movements;
      during horizontal movements two load force peaks result from both acceleratory
      and deceleratory phases of the movement. During performance with normal finger
      sensibility grip force was modulated in parallel with fluctuations of load force
      during vertical and horizontal movements. The grip force profile adopted to the
      varying load force profile during the transition from the vertical to the
      horizontal position. The maximum grip force occurred at the same time of maximum
      load force irrespective of the movement plane. During both subjects' first
      experience of digital anesthesia the object slipped from the grasp during
      rotation to the horizontal plane. During the following trials with anesthetized
      fingers subjects substantially increased their grip forces, resulting in elevated
      force ratios between maximum grip and load force. However, grip force was still
      modulated with the movement-induced load fluctuations and maximum grip force
      coincided with maximum load force during vertical and horizontal movements. This
      implies that the elevated force ratio between maximum grip and load force does
      not alter the feedforward system of grip force control. Cutaneous afferent
      information from the grasping digits seems to be important for the economic
      scaling of the grip force magnitude according to the actual loading conditions
      and for reactive grip force adjustments in response to load perturbations.
      However, it plays a subordinate role for the precise anticipatory temporal
      coupling between grip and load forces during voluntary object manipulation.

PMID- 11962647
TI  - Responses of spinohypothalamic tract neurons in the thoracic spinal cord of rats
      to somatic stimuli and to graded distention of the bile duct.
AB  - Anatomical studies indicate that a relatively large percentage of
      spinohypothalamic tract (SHT) neurons are located within thoracic spinal
      segments. The aim of this study was to characterize the responses of SHT neurons
      in these segments of rats to innocuous and noxious stimulation of the skin and of
      a visceral structure, the bile duct. In addition, we attempted to determine the
      trajectories of the axons of the examined neurons within the diencephalon and
      brainstem. Fifty-three SHT neurons were recorded within segments T8-T13 in
      urethane anesthetized rats. Each cell was antidromically activated using current
      pulses < or = 30 microA delivered from the tip of an electrode located within the
      contralateral hypothalamus. The recording points were located in the superficial
      dorsal horn (9) and deep dorsal horn (44). All examined SHT neurons had receptive
      fields on the posterior thorax and anterior and ventral abdomen of the
      ipsilateral side. Ninety percent of the 41 SHT neurons responded exclusively (13)
      or preferentially (24) to noxious cutaneous stimuli. Thirteen of 27 (48%)
      examined units were activated by forceful distention of the bile duct. Response
      thresholds ranged from 30 to 40 mmHg. Responses incremented as pressures were
      increased to 50-80 mmHg. The axons of 22 of 28 (79%) examined SHT neurons
      appeared to cross the midline within the hypothalamus and terminate in the
      ipsilateral hypothalamus, thalamus or midbrain. The results indicate that SHT
      neurons in thoracic spinal cord of rats are capable of conveying somatic and
      visceral nociceptive information from the bile duct directly to targets at
      various levels of the brain bilaterally.

PMID- 11962648
TI  - Cold and warmth perception mapped for age, gender, and body area.
AB  - Reference data on cold and warmth perception at three different body areas are
      provided based on 24 young (20-30 years) and 24 elderly (55-65 years) healthy
      women and men. Perception thresholds (method of limits), perceived intensity
      (free-number magnitude estimation), and perceived quality (verbal descriptors)
      were assessed for cold and for warmth at thenar, the upper arm, the knee, and the
      foot. Inter-individual comparison of perceived-intensity scales for cold and
      warmth was achieved by a Master Scaling procedure utilizing thenar as a reference
      area. Perception thresholds showed gender difference for cold at thenar, and
      interaction effect of age and gender for heat-pain tolerance at the upper arm. In
      contrast, perceived intensity of cold and warmth showed multiple effects of age,
      gender, and specific body area (also for the nociceptive channels). For instance,
      at the knee, elderly women's perceived intensity for stimulation in the
      nociceptive range was elevated for both cold and warmth, as compared to young
      women and men, and to elderly men. Conversely, at the upper arm, elderly women's
      perceived intensity for the corresponding nociceptive range was lowered, as
      compared to young women and young men, and to elderly men. At the foot, both
      elderly women's and men's perceived intensity of cold and warmth was lowered, as
      compared to young women and men. Overall, the perceived quality of perceptions
      did not differ between groups. The present findings on age differences in
      perceived intensity of cold and warmth at the upper arm, knee and foot in healthy
      women and men provide reference data hitherto lacking for diagnostic work in
      patients with somatosensory dysfunctions and ongoing pain.

PMID- 11962649
TI  - Optimization of diamine bridges in glutaraldehyde treated bioprosthetic aortic
      wall tissue.
AB  - OBJECTIVE: Bioprosthetic calcification can be significantly mitigated by both
      increased concentrations of glutaraldehyde (GA) and the introduction of diamine
      (DA) bridges. The purpose of the present study was to evaluate whether an optimal
      effect of DA-enhanced fixation can be achieved by titration of dialdehyde and
      diamine concentrations. METHODS: Porcine aortic roots were fixed at 0.05% GA
      (under-fixation) or 0.2% GA and 0.7% GA (commercial fixation). An interim step of
      DA treatment (L-Lysine; 0, 25, 50 or 100 mM; 37 degrees C; 2 days) was followed
      by completion of the GA fixation (37 degrees C; 5 days). Aortic wall coupons (12
      mm) were punched out and implanted subcutaneously into seven-week old Long-Evans
      rats for 60 days. Calcium content was assessed by atomic absorption spectroscopy
      and histology. RESULTS: Increasing the L-Lysine concentrations beyond 25 mM was
      essential to achieve the anti-calcific effect of DA-enhanced fixation. This
      effect was proportional to the GA concentrations applied. Compared to non
      enhanced GA fixation (0 mM DA), calcification increased by 17.4% (p = 0.2114) in
      0.05% fixed tissue but decreased by 32.0% (p < 0.0001) and 45.1% (p < 0.0002) in
      0.2% and 0.7% GA, respectively, when the DA concentration was 100 mM.
      Histologically the extent, but not the pattern of calcification, was affected.
      CONCLUSION: The calcium mitigating effect of diamine-treatment as an interim step
      of glutaraldehyde fixation is proportional to the GA concentration applied.
      Within commercial 0.7% GA fixation 100 mM DA has the potential to practically
      halve aortic wall calcification.

PMID- 11962650
TI  - Properties of heat-treated calcium phosphate coatings deposited by high-velocity
      oxy-fuel (HVOF) spray.
AB  - The influence of crystallization, upon heat treatment, on the properties of high
      velocity oxy-fuel (HVOF) sprayed hydroxyapatite (HA) coatings was investigated.
      The characterization of the HA coating was performed by X-ray diffraction (XRD)
      and Fourier Transform Infrared Spectroscopy (FTIR). Differential Scanning
      Calorimeter (DSC) was employed to determine the crystallization temperature of
      the amorphous phase in an as-sprayed HA coating. The study demonstrated the
      effect of crystallization on the coating properties by considering the changes in
      materials chemistry, crystallinity level, and mechanical performance. Results
      showed that complete crystallization of the amorphous phase occurred at
      approximately 700 degrees C and the crystallization temperature was dependent on
      sample heating rate in the DSC test. The changes of ion groups were detected by
      FTIR, before and after the phase transformation. The crystallization of the
      coating after annealing at 750 degrees C resulted in a significant increase of
      the coatings' adhesive strength and shear strength, which attained maximum values
      34 +/- 3 and 14.1 -/+ 0.8 MPa, respectively. Young's modulus increased from 21 +/
      1 to 25 +/- 2 GPa. Microhardness measurements confirmed the changes in coating
      properties. It is also found that the transformation from the amorphous phase has
      crystalline HA as the only resultant phase detected by XRD.

PMID- 11962651
TI  - Biocomposites of non-crosslinked natural and synthetic polymers.
AB  - Biocomposite films comprising a non-crosslinked, natural polymer (collagen) and a
      synthetic polymer, poly(epsilon-caprolactone) (PCL), have been produced by
      impregnation of lyophilised collagen mats with a solution of PCL in
      dichloromethane followed by solvent evaporation. This approach avoids the
      toxicity problems associated with chemical crosslinking. Distinct changes in film
      morphology, from continuous surface coating to open porous format, were achieved
      by variation of processing parameters such as collagen:PCL ratio and the weight
      of the starting lyophilised collagen mat. Collagenase digestion indicated that
      the collagen content of 1:4 and 1:8 collagen:PCL biocomposites was almost totally
      accessible for enzymatic digestion indicating a high degree of collagen exposure
      for interaction with other ECM proteins or cells contacting the biomaterial
      surface. Much reduced collagen exposure (around 50%) was measured for the 1:20
      collagen:PCL materials. These findings were consistent with the SEM examination
      of collagen:PCL biocomposites which revealed a highly porous morphology for the
      1:4 and 1:8 blends but virtually complete coverage of the collagen component by
      PCL in the 1:20 samples. Investigations of the attachment and spreading
      characteristics of human osteoblast (HOB) cells on PCL films and collagen:PCL
      materials respectively, indicated that HOB cells poorly recognised PCL but
      attachment and spreading were much improved on the biocomposites. The non
      chemically crosslinked, collagen:PCL biocomposites described are expected to
      provide a useful addition to the range of biomaterials and matrix systems for
      tissue engineering.

PMID- 11962652
TI  - Development of a 'mechano-active' scaffold for tissue engineering.
AB  - In this study. we investigate the potential for manipulating bone cell
      mechanotransducers in tissue engineering. Membrane ion channels such as voltage
      operated calcium channels (VOCC) have been shown to be a critical component of
      the bone cell transduction pathway with agonists and inhibitors of this pathway
      having profound effects on the load signal. By encapsulating a calcium channel
      agonist with slow release within a poly(L-lactide) (PLLA) scaffold, we can
      generate a 'mechano-active' scaffold for use in skeletal tissue engineering. PLLA
      scaffolds with and without a calcium channel agonist, BAY K8644, were seeded with
      primary human bone cells or the human MG63 bone cell line and cultured for 13
      weeks followed by mechanical stimulation with a four-point bending model. Our
      results show that addition of the agonist for slow release is sufficient to
      enhance the load-related responses in bone cells within the scaffolds.
      Specifically, collagen type I expression and the ratio of alkaline phosphatase to
      protein are elevated in response to cyclical mechanical stimulation of
      approximately 1000 microstr which is then further enhanced in the mechano-active'
      scaffolds. As the agonists only act when the calcium channels are open by
      attenuating the calcium flux, the stimulation is specifically targeted to
      scaffolds subjected to load either in vitro or ultimately in vivo. Our results
      suggest that manipulating the VOCC and attenuating the opening of the calcium
      channels may be an effective technique to amplify matrix production via
      mechanical stimulation which may be applied to bone tissue engineering and
      potentially engineering of other load-bearing connective tissues.

PMID- 11962653
TI  - Novel hydrogels as supports for in vitro cell growth: poly(ethylene glycol)- and
      gelatine-based (meth)acrylamidopeptide macromonomers.
AB  - Conversion of amine groups with vinyl-functional azlactones occurs at room
      temperature under physiological conditions to afford (meth)acrylamidopeptide
      functional macromonomers. Such macromonomers based upon alpha,omega
      bisaminopropyl-terminated poly(ethylene glycol) and gelatine were prepared and
      copolymerized to produce novel hydrogel networks. Compression modulus was
      inversely proportional to the water content (EWC), which was controlled primarily
      by the PEG macromonomers with non-modified gelatine, the covalent attachment of
      gelatine to the hydrogel network gave substantially improved performance with
      respect to both, adhesion and growth of human fibroplasts.

PMID- 11962654
TI  - Biological clearance of HEMA in guinea pigs.
AB  - No toxicokinetic data are available about the dental composite component 2
      hydroxyethylmethacrylate (HEMA) in vivo in the literature. Therefore, the
      excretion of HEMA in feces and urine in vivo and, using the pendular perfusion
      technique with segments of jejunum and colon, in the biliary and enteric
      excretion in situ were investigated in anesthetized guinea pigs. In the in situ
      experiments, guinea pigs (n = 4) received HEMA (0.02 mmol/kgbw labelled with a
      tracer dose 14C-HEMA 0.3 kBq/gbw) injected into the jugular vein. In the in vivo
      experiments, guinea pigs (n = 4) received HEMA (+ 14C-HEMA, same dose as above)
      via gastric tube. Urine and feces were collected for 24h. In the in situ
      experiments, organs from guinea pigs were removed 60 min after the beginning of
      the experiment, and then the 14C-radioactivity was measured. During the 60 min
      perfusion period the calculated amount of 14C-activity excreted into the total
      jejunum and colon was 6.0 +/- 1.0% and 2.7 +/- 0.7% of the dose administered,
      respectively (mean +/- sem). Of the 14C-HEMA dose, 5.3 +/- 0.3% was found in the
      bile. Significantly (p < 0.05) higher bile/blood concentration ratios were found
      at 10-40 min after the injection of HEMA, as compared to the ratio at 60 min. The
      total 14C-recovery in all organs tested was 20.0 +/- 2.6%. During 24h the amounts
      of 14C-activity excreted in the feces and urine were 1.1 +/- 0.1% or 17.1 +/-
      1.50% of the dose administered, respectively (mean +/- sem). The total 14C
      recovery in all organs tested was 11.6 +/- 0.6%. In a second series of in vivo
      experiments, exhaled air from the animals was captured during the 24h
      experimental period. 14C was exhaled to 63.6 +/- 2.11% of the administered 14C
      HEMA dose (mean +/- sem; n = 4) as 14C-carbondioxide. The results indicate a
      rapid clearance of 14C-HEMA and/or 14C-HEMA metabolite(s) from the organism,
      exhalation being the major route of elimination.

PMID- 11962655
TI  - In vitro evaluation of poly(epsilon-caprolactone-co-DL-lactide)/ bioactive glass
      composites.
AB  - In vitro bioactivity of composites of poly(epsilon-caprolactone-co-DL-lactide)
      P(CL/DL-LA) containing different amounts (40, 60 and 70 wt%) of bioactive glass,
      S53P4, was evaluated. Two ranges of granule size of bioactive glass (< 45 microm
      and 90-315 microm) were blended with P(CL/DL-LA) copolymer in a batch mixer. The
      composites were characterised by dynamic mechanical thermal analysis. The
      molecular weight and the melting temperature of the copolymer matrix were
      adjusted to enable the application of the composite material by injection below
      50 degrees C. Formation of Ca-P deposition on the surface of the composites after
      dissolution in simulated body fluid at 37 degrees C was recorded by scanning
      electron microscopy. Degradation of the composite material was measured by water
      absorption and changes in the average molecular weights as a function of the
      dissolution time. In vitro bioactivity was found to be dependent on the weight
      fraction and granule size range of the bioactive glass used. The presence of the
      bioactive filler also accelerated the degradation compared with the neat polymer
      sample.

PMID- 11962656
TI  - A novel bioactive and magnetic biphasic material.
AB  - A novel biphasic material has been synthetised from a sol-gel-derived glass (Si
      Ca-P) and a glass-ceramic obtained from a melt-derived glass (Si-Ca-Fe). Both
      components of such a biphasic mixture are bioactive, but with different kinetics
      for the growth of an apatite-like layer on the surface of these materials,
      needing only one day for the sol-gel-derived glass and one month for the glass
      ceramic. The glass-ceramic shows magnetic properties. The biphasic material,
      obtained from a mixture 1:1 of these components, is bioactive, and its surface is
      coated after 15 days of soaking in SBF. The biphasic material also exhibited
      magnetic behaviour, useful for hyperthermia.

PMID- 11962657
TI  - Thrombomodulin expression in endothelial cells after contact with bone cement.
AB  - The expression of thrombomodulin after contact with CMW 1 bone cement extracts
      was studied in human umbilical vein endothelial cells. Cement extracts after 1 h
      and 7-day curing induced no significant variations in thrombomodulin antigen
      levels and in mRNA expression. Significant increase of thrombomodulin was
      observed when endothelial cells were treated with all-trans retinoic acid (ATRA).
      ATRA induced the increase of thrombomodulin also in cells incubated with cement
      extracts. These results suggest that CMW 1 bone cement does not impair the
      expression of thrombomodulin in endothelial cells.

PMID- 11962658
TI  - Characterization of biodegradable drug delivery vehicles with the adhesive
      properties of leukocytes.
AB  - The site-specific expression of selectins (E- and P-selectin) on endothelial
      cells of blood vessels during inflammation provides an opportunity for the
      targeted delivery of anti-inflammatory drugs to inflammatory sites. Previous work
      in our laboratory has shown that artificial capsules with the adhesive properties
      of leukocytes can be made by attaching leukocyte adhesive ligands to polystyrene
      microspheres. In this work, we have adapted this technology to create a targeted
      delivery system using biodegradable, poly lactic-co-glycolic-acid (PLGA)
      microspheres. Biotinylated-Sialyl Lewis(x) (sLe(x)), a carbohydrate that serves
      as a ligand to selectins, was attached to the surface of avidin-linked PLGA
      microspheres. These carbohydrate-coated microspheres mimic the adhesive behavior
      of leukocytes on selectins in flow chambers, displaying slow rolling under flow.
      The rolling velocities displayed by sLe(x)-coated microspheres were similar to
      those displayed by leukocytes rolling on P- or E-selectin coated surfaces, and
      these rolling velocities, which relate to the residence time of the capsules, can
      be tuned by changing the density of carbohydrate residues on microsphere
      surfaces. We have also demonstrated that these microspheres will release model
      drugs on a time scale of several days. Therefore, we have made a targeted drug
      delivery vehicle that mimics the adhesive properties of leukocytes and is
      biodegradable.

PMID- 11962659
TI  - 22 week assessment of bladder acellular matrix as a bladder augmentation material
      in a porcine model.
AB  - Previous studies on the reconstruction of porcine bladder using bladder acellular
      matrix allograft (BAMA) have indicated positive preliminary results with respect
      to graft shrinkage and cellular repopulation. The current study was conducted to
      investigate the feasibility of using BAMA in a similar model of bladder
      reconstruction out to longer time frames (22 weeks). At predetermined time
      points, the macroscopic, histological and mechanical properties of explanted
      native and BAMA tissues were evaluated and compared. Macroscopically, contracture
      of the BAMA was observed. The peripheral regions of the grafts experienced
      extensive cellular repopulation. Towards the centre however, all grafts were
      consistently devoid of organized smooth muscle bundles and a well-developed
      urothelium. An alteration in both the amount and organization of collagen was
      also observed within this region. Significant differences (p < 0.05) in the
      rupture strain and the elastic modulus of the BAMA compared to native bladder
      tissue appear to correlate with macroscopic graft contracture as well as the
      fibroproliferative tissue response of the matrix.

PMID- 11962660
TI  - The glass ionomer cement: the sources of soluble fluoride.
AB  - This study aimed to investigate certain processes of fluoride production which
      enable glass ionomer cements to leach fluoride. Two fluoroaluminosilicate
      glasses, G338 and LG26 were used. The free and total fluoride which could be
      dissolved from the glasses was measured, before and after acetic acid washing.
      Both glasses contained appreciable amounts of soluble fluoride prior to any acid
      treatment. The latter process reduced the amount to some 75% of the original
      levels. Replacing the customary polymeric acid with propionic acid produced a
      cement which disintegrated in water allowing the amount of fluoride generated by
      the cement forming process to be measured. Cement production increased soluble
      fluoride by a further 3%. Both glasses behaved similarly when undergoing the
      various processes. G338 produced significantly greater quantities of fluoride, of
      the order of 10, compared with LG26 although containing only three times the
      amount of fluoride in the glass formula. A substantial proportion, over half, of
      the total fluoride was complexed especially after contact with cement and when
      G338 was used. During the period of the experiment, 21 days, total fluoride
      release did not seem to depend on the square root of time.

PMID- 11962661
TI  - The use of a coin shaped implant for direct in situ measurement of attachment
      strength for osseointegrating biomaterial surfaces.
AB  - Most animal models currently used to study the retention of implants in bone are
      influenced by shear forces introduced during the retention test. This is mainly
      due to the implant design, which most often are cylindrical, conical or threaded.
      In these models interlocking between bone and implant surface will increase the
      effect of genuine bone bonding and thus give a false positive outcome. The
      purpose of the present study was to establish a model for testing functional
      attachment of implants in situ, with minimal influence of interlocking and shear
      forces. The model involves the use of flat coin shaped implant placed onto the
      cortical bone of rabbit tibia without mechanical fixation to the bone. The
      implant is passively retained on the cortical bone by a titanium band retainer.
      During the healing period, the contact between the coin shaped implants and the
      bone is restricted to the flat test surfaces. To prevent interlocking effects
      from lateral bone attachments a polytetrafluoroethylene (PTFE) cap covering the
      vertical and the upper faces of the implants were used. The tensile test was
      performed with a gradual, calibrated pull, perpendicular to the bone-implant
      interface. This pullout model makes it possible to study the kinetics and
      strength of bone bonding with negligible influence of shear forces or mechanical
      interlocking.

PMID- 11962662
TI  - Nucleation of biomimetic Ca-P coatings on ti6A14V from a SBF x 5 solution:
      influence of magnesium.
AB  - Biomimetic Calcium-Phosphate (Ca-P) coatings were applied by using 5 times
      concentrated Simulated Body Fluid (SBF x 5) using Carbon Dioxide gas. This
      process allows the deposition of a uniform Ca-P coating within 24 h. A previous
      study of our process emphasized the importance of hydrogenocarbonate ions (HCO
      3), a crystal growth inhibitor. The aim of the present study was to investigate
      the role of the other crystal growth inhibitor present in SBF x 5, Magnesium
      (Mg2+), on the Ca-P coating formation. Several SBF x 5 solutions were prepared
      with various Mg2+ and HCO3 contents. No Ca-P deposits were detected on Ti6A14V
      substrate soaked for 24h in a Mg-free SBF x 5 solution, whereas by increasing HCO
      3 content in a Mg-free SBF x 5 solution, a Ca-P coating developed on Ti6A14V
      substrate. Therefore, it appeared that Mg2+ has a stronger inhibitory effect on
      apatite crystal growth than HCO-3. Nevertheless, Mg2+ plays also another
      important role as suggested by depth profile X-ray Photoelectron Spectroscopy
      (XPS) of the Ca-P coating obtained from SBF x 5 solution. Ca2+ and Mg2+ contents
      increased significantly at the titanium/coating interface. Therefore, Ca2+ and
      Mg2+ initiated Ca-P coating from SBF x 5 solution. The relatively high
      interfacial concentration in Mg2+ favors heterogeneous nucleation of tiny Ca-P
      globules onto the substrate. So physical adhesion is enhanced at the early stage
      of the coating formation.

PMID- 11962663
TI  - The influence of short-term water storage on the flexural properties of
      unidirectional glass fiber-reinforced composites.
AB  - OBJECTIVE: The aim of this study was to determine flexural properties of
      unidirectional E-glass fiber-reinforced composite (FRC) with polymer matrices of
      different water sorption properties. METHODS: Rhombic polymer and FRC test
      specimens made of three commercially available diacrylate resin (Sinfony
      Activator, Triad Gel, 3M Scotchbond Adhesive) and different volume fractions of
      fibers were tested with three-point bending test according to ISO 10477 after
      storing in water for 30 days. Water sorption of specimens was also measured.
      RESULTS: Flexural strength of specimens with 45 vol% fraction E-glass fibers
      varied from 759 to 916 MPa in dry conditions. Water-stored specimens showed
      flexural strengths of 420-607 MPa. ANOVA analysis revealed that the fiber-volume
      fraction and the water sorption of the polymer matrix had a significant effect (p
      < 0.001) on the flexural properties. Dehydration of specimens recovered the
      mechanical properties. Decrease of flexural properties after water immersion was
      considered to be mainly caused by the plasticizing effect of water and the
      decrease depended on water sorption. SIGNIFICANCE: Use of polymers with low-water
      sorption seems to be beneficial in order to optimize the flexural properties of
      FRC.

PMID- 11962664
TI  - Thermo-mechanical analysis of a compliant poly(carbonate-urea)urethane after
      exposure to hydrolytic, oxidative, peroxidative and biological solutions.
AB  - AIMS: To date, there is still a great need for a fully viable small diameter (< 6
      mm) polymeric vascular graft. Currently in such low flow locations, non-elastic
      expanded polytetrafluoroethylene (ePTFE) is the best available but it is quite
      inferior to autologous saphenous vein since it fails due to intimal hyperplasia
      caused by compliance mismatch between the graft and elastic host artery.
      Recently, a novel compliant poly(carbonate-urea)urethane vascular graft whose
      trade name is MyoLink has been developed. In this article, we report the findings
      of a thermo-mechanical analysis of the polymers chemistry postexposure to in
      vitro solutions comprised of hydrolytic, oxidative, peroxidative and biological
      media. METHODS AND MATERIALS: The following degradative solutions were used in
      vitro: plasma fractions I-IV; phospholipase A2 (PLA); cholesterol esterase (CE)
      and solutions of H2O2/CoCl2, t-butyl peroxide/CoCl2 (t-but/CoCl2) and
      glutathione/t-butyl peroxide/ CoCl2 (glut/t-but/CoCl2). The MyoLink graft was
      compared against a conventional poly(ether)urethane (Pulse-Tec). All the graft
      specimens were 100 mm in length (5.0 mm ID) and were incubated in the latter
      solutions at 37 degrees C for 70 days in total. The following thermo-mechanical
      methods were used to analyse both graft types: thermo-mechanical analysis (TMA)
      and dynamic mechanical thermal analysis (DMTA). RESULTS: Incubation of Pulse-Tec
      in plasma fractions I-IV, PLA and CE reveals only one observable modification: an
      increase in the size of the low temperature, melting phase. But incubation in
      H2O2/CoCl2, and t-but/CoCl2 leads to an increase in the polymeric phase
      separation coupled with an enlargement in the size of the low temperature melting
      crystalline phase in Pulse-Tec. The glut/t-but/CoCl2 solution leads to a phase
      separation between the hard and soft segment domains, coupled with an increase of
      the internal order within the hard segment domains in Pulse-Tec. The only system
      in which MyoLink degraded was glut/t-but/CoCl2. In this system, an increase of
      the phase separation coupled with a simultaneous increase of the crystal size of
      the low-temperature melting crystalline phase occurred. CONCLUSION: This study
      shows dramatic changes in the chemistry of the soft and hard segments occurred in
      the case of the conventional poly(ether)urethane Pulse-Tec graft material. Such
      changes were not manifested in the majority of solutions in the case of MyoLink
      but a hydrolytic-led degradation of the carbonate soft segment was evidenced only
      in the glut/t-but/CoCl2 system.

PMID- 11962665
TI  - Crystallinity and solubility characteristics of hydroxyapatite adsorbed amino
      acid.
AB  - Hydroxyapatite (HAp) was synthesized in the presence of a variety of amino acids
      in order to investigate the effect of amino acid on the crystallinity and the
      solubility characteristics of HAp in the HAp-synthesizing condition. In the
      results of X-ray diffraction analysis, HAp synthesized in the presence of glycine
      (HAp-Gly), serine (HAp-Ser), aspartic acid (HAp-Asp) and glutamic acid (HAp-Glu)
      showed poor crystallinity compared with HAp synthesized in the absence of amino
      acid (HAp-con). The results of Fourier transform infrared spectroscopy suggested
      the adsorption of these amino acids on HAp. Scanning electron microphotographs
      showed that the size and morphology of HAp adsorbed amino acids changed
      significantly. Furthermore, the solubility of these HAps increased significantly
      compared to HAp-con, each differing in four amino acids. However, other amino
      acids did not affect the crystallinity and morphology of HAp and had no
      significant change in their solubility. Collectively, this study suggests that
      the crystallinity and the solubility of synthesized HAp are different owing to
      the variation of amino acids in the HAp synthesizing condition. It is expected
      that digestion-regulated HAp materials could be synthesized by using amino acid
      in their synthesizing condition.

PMID- 11962666
TI  - Reproducibility of the mechanical properties of Vivostat system patient-derived
      fibrin sealant.
AB  - Conventional "autologous" fibrin sealants, prepared from fibrinogen concentrates
      are inconsistent in their physical properties; this reflects the wide variation
      in the fibrinogen level of the single donor plasma from which they are made. In
      contrast, the Vivostat System produces a fibrin sealant of reproducible
      concentration and mechanical properties that are independent of the source plasma
      fibrinogen concentration. Fibrin solution concentrations prepared with the
      Vivostat System were 22.0 +/- 0.7 mg/ml (95% CI) with a coefficient of variation
      [CV] of 10.6% from samples of source plasma with a range of fibrinogen
      concentration between I and 6 mg/ml (mean 3.28 +/- 0.38 mg/ml (95% CI), 37% CV).
      Values of viscoelastic and tensile parameters after 11 min and 1 h, respectively,
      were: storage modulus (G') 891.5 +/- 72.9 Pa, 16.2% CV; loss modulus (G") 98.7 +/
      9.8 Pa, 23.2% CV; loss tangent (tan delta) 0.1093 +/- 0.0054, 9.8% CV; tensile
      strength 33.2 +/- 2.6kPa, 24.7% CV; extension at break 103 +/- 13%, 22.6% CV;
      Young's modulus 12.0 +/- 1.0 kPa, 16.6% CV. In the clinical setting this
      reproducibility provides the surgeon with a patient-derived fibrin sealant that
      can be expected to perform similarly from patient to patient.

PMID- 11962667
TI  - Comparison of the antioxidant properties of HYAFF-11p75, AQUACEL and hyaluronan
      towards reactive oxygen species in vitro.
AB  - In chronic wounds, a number of host factors are released which perpetuate the
      inflammatory process, including polymorphonuclear leukocyte (PMN)-derived
      reactive oxygen species (ROS), such as superoxide radical (O2*-) and hydroxyl
      radical (*OH) species. The glycosaminoglycan. hyaluronan, has been shown to act
      as an antioxidant towards ROS, although the potential for biomaterials, such as
      HYAFF -11p75 (the 75% benzyl ester of hyaluronan) and AQUACEL
      (carboxymethylcellulose), to act in this manner has yet to be elucidated. This
      study compared the antioxidant properties of high and low molecular weight
      hyaluronan (HMWT HA and LMWT HA), HYAFF -11p75, AQUACEL and an AQUACEL
      /hyaluronan composite (AQUACEL /HA) against O2*- and *OH. The antioxidant
      capacities of each material were assessed by their ability to inhibit cytochrome
      C reduction by O2*- fluxes, generated via the oxidation of hypoxanthine by
      xanthine oxidase, and their inhibition of 2-deoxy-D-ribose degradation by *OH
      fluxes, generated by the reaction of hydrogen peroxide (H2O2) and iron (Fe2+).
      All materials studied possessed dose dependent antioxidant properties towards O2*
      , with HYAFF 11p75 having the greatest antioxidant potential towards these
      species, followed by AQUACEL, HMWT HA, AQUACEL /HA and LMWT HA. Only HMWT HA
      exhibited dose dependent antioxidant properties towards *OH at the fluxes
      examined. Gas chromatography/mass spectrometry analysis implied that ester bonds
      between the hyaluronan backbone and benzyl groups of HYAFF -11p75 are highly
      susceptible to O2*- hydrolysis, with the de-esterified benzyl alcohol being
      rapidly degraded in the presence of *OH. This data supports the hypothesis that
      HYAFF -11p75 has greater antioxidant capacity towards O2*-, due to the esterified
      benzyl groups providing alternative sites for O2*- attack other than the
      hyaluronan backbone of HYAFF -11p75 itself and explains the inability of HYAFF 
      11p75 to scavenge *OH, due to benzyl alcohol degradation by *OH. The antioxidant
      activities of these biomaterials, particularly HYAFF -11p75 and AQUACEL, towards
      O2*- could be beneficial, as the scavenging of PMN-derived O2*- may remove
      initial sources of O2*- and further prevent the secondary formation of *OH. These
      ROS are thought to be a primary causal factor for the extensive degradation and
      metabolic alterations observed in chronic wounds.

PMID- 11962668
TI  - Hydrothermal modification of titanium surface in calcium solutions.
AB  - Hydrothermal modification of a titanium surface in calcium solutions was
      performed. The apatite precipitation on the modified surface in Hanks' solution,
      as a simulated body fluid, was evaluated and the surface microstructure changes
      after the modification were characterized by thin-film X-ray diffractometry (TF
      XRD) and X-ray photoelectron spectroscopy (XPS). Hydrothermal modification in CaO
      solution enhanced the precipitation of apatite on the titanium surface. High pH,
      high pressure and high temperature of the CaO solution increased the thickness of
      the surface-modified layer and enhanced the synthesis of calcium titanate which
      possibly promoted the precipitation of apatite in Hanks' solution. Hydrothermal
      modification in CaCl2 solution, on the other hand, showed reverse effects. The
      modification of titanium in CaO solution with hydrothermal treatment is expected
      to result in excellent osteointegration and can be easily performed by using an
      autoclave, a clinical apparatus widely used.

PMID- 11962669
TI  - From circadian rhythms to cancer chronotherapeutics.
AB  - Mammalian circadian rhythms result from a complex organization involving
      molecular clocks within nearly all "normal" cells and a dedicated neuroanatomical
      system, which coordinates the so-called "peripheral oscillators." The core of the
      central clock system is constituted by the suprachiasmatic nuclei that are
      located on the floor of the hypothalamus. Our understanding of the mechanisms of
      circadian rhythm generation and coordination processes has grown rapidly over the
      past few years. In parallel, we have learnt how to use the predictable changes in
      cellular metabolism or proliferation along the 24h time scale in order to improve
      treatment outcome for a variety of diseases, including cancer. The
      chronotherapeutics of malignant diseases has emerged as a result of a consistent
      development ranging from experimental, clinical, and technological prerequisites
      to multicenter clinical trials of chronomodulated delivery schedules. Indeed
      large dosing-time dependencies characterize the tolerability of anticancer agents
      in mice or rats, a better efficacy usually results from treatment administration
      near the least toxic circadian time in rodent tumor models. Programmable in time
      multichannel pumps have allowed to test the chronotherapy concepts in cancer
      patients and to implement chronomodulated delivery schedules in current practice.
      Clinical phase I and II trials have established the feasibility, the safety, and
      the activity of the chronotherapy schedules, so that this treatment method has
      undergone further evaluation in international multicenter phase III trials.
      Overall, more than 2,000 patients with metastatic disease have been registered in
      chronotherapy trials. Improved tolerability and/or better antitumor activity have
      been demonstrated in randomized multicenter studies involving large patient
      cohorts. The relation between circadian rhythmicity and quality of life and even
      survival has also been a puzzling finding over the recent years. An essential
      step toward further developments of circadian-timed therapy has been the recent
      constitution of a Chronotherapy cooperative group within the European
      Organization for Research and Treatment of Cancer. This group now involves over
      40 institutions in 12 countries. It is conducting currently six trials and
      preparing four new studies. The 19 contributions in this special issue reflect
      the current status and perspectives of the several components of cancer
      chronotherapeutics.

PMID- 11962670
TI  - Rhythms in human bone marrow and blood cells.
AB  - In 24h studies of bone marrow (BM), circadian stage-dependent variations were
      demonstrated in the proliferative activity of BM cells from subsets of 35 healthy
      diurnally active men. On an average, the percentage of total BM cells in
      deoxyribonucleic acid (DNA) synthesis phase was 188% greater at midday than at
      midnight (circadian rhythm: p = 0.018; acrophase or peak time of 13: 16h).
      Patients with malignant disease (n = 15) and a normal cortisol circadian rhythm
      showed higher fractions of BM cells in S-phase at midday. Colony-forming units-
      granulocyte/macrophage (CFU-GM), an indicator of myeloid progenitor cells, showed
      the same circadian variation as DNA S-phase (average range of change or ROC =
      136%; circadian rhythm: p < 0.001; acrophase of 12:09h). Deoxyribonucleic acid S
      phase and CFU-GM in BM both showed a circannual rhythm (p = 0.015 and 0.008) with
      an identical acrophase of August 12. The daily peak in BM glutathione content, a
      tripeptide involved in cellular defense against cytotoxic damage, preceded BM
      proliferative peaks by 4-5 h (ROC = 31-90%; circadian rhythm: p = 0.05; acrophase
      of 08:30h). Myeloid (ROC = 57%; circadian rhythm: p = 0.056; acrophase at 08:40h)
      and erythroid (ROC = 26%; circadian rhythm: p = 0.01; acrophase of 13:01h)
      precursor cells were positively correlated (r = 0.41; p < 0.001), indicating a
      circadian temporal relationship and equal influence on S-phase of total BM cells.
      Yield of positive selected CD34+ progenitor stem cells also showed significant
      circadian variation (ROC = 595%; circadian rhythm: p = 0.02; acrophase of
      12:40h). Thus, the temporal synchrony in cell cycling renders BM cells more
      sensitive at specific times to hematopoietic growth factors and cell cycle
      specific cytotoxic drugs. Moreover, proper timing of BM harvesting may improve
      progenitor cell yield. When using marker rhythms in the blood to allow for
      individualized timing of BM procedures, the times of low values in white blood
      corpuscles, neutrophils, and lymphocytes and high values in cortisol were
      predictive of the times of highest BM erythroid, myeloid, and total S-phase
      numbers occurring in the following 12 h.

PMID- 11962671
TI  - Rhythms in human gastrointestinal mucosa and skin.
AB  - Rhythmicity in cell proliferation is well established in the gastrointestinal
      tract and skin, both in rodents and humans. This is the basis for studies on the
      timing of both chemotherapy and radiotherapy. More recently, circadian rhythm
      studies of cell-cycle proteins have confirmed earlier findings based on thymidine
      labeling and flow cytometry. The genetic control of circadian rhythms has been
      elucidated recently and a possible connection between the circadian clock and the
      timing of cell-cycle events has been suggested. The data for gastrointestinal
      mucosa and skin are reviewed and the potential clinical implications of these
      results are discussed.

PMID- 11962672
TI  - Marker rhythms of circadian system function: a study of patients with metastatic
      colorectal cancer and good performance status.
AB  - Cancer patients may exhibit normal or altered circadian rhythms in tumor and
      healthy tissues. Four rhythms known to reflect circadian clock function were
      studied in 18 patients with metastatic colorectal cancer and good performance
      status. Rest-activity was monitored by wrist actigraphy for 72 h before
      treatment, and its circadian rhythm was estimated by an autocorrelation
      coefficient at 24h and a dichotomy index that compared the activity level when in
      and out of bed. Blood samples (9-11 time points, 3-6 h apart) were drawn on day 1
      and day 4 of the first course of chronochemotherapy (5-fluorouracil: 800
      mg/m2/day; folinic acid: 300 mg/m2/day; oxaliplatin: 25 mg/m2/day). Group 24h
      rhythms were validated statistically for plasma concentrations of melatonin, 6
      alpha-sulfatoxymelatonin, and cortisol and for lymphocyte counts. Significant
      individual 24h rhythms were displayed in melatonin by 15 patients, cortisol by
      seven patients, lymphocytes by five patients, and prominent circadian rhythms in
      activity were displayed by 10 patients; only one patient exhibited significant
      rhythms in all the variables. The results suggest the rhythms of melatonin,
      cortisol, lymphocytes, and rest/activity reflect different components of the
      circadian system, which may be altered differently during cancer processes. Such
      24h rhythm alterations appeared to be independent of conventional clinical
      factors.

PMID- 11962673
TI  - Time-patterned drug administration: insights from a modeling approach.
AB  - The physiological effects of a drug depend not only on its molecular structure
      but also on the time-pattern of its administration. One of the main reasons for
      the importance of temporal patterns in drug action is biological rhythms-
      particularly those of circadian period. These rhythms affect most physiological
      functions as well as drug metabolism, clearance, and dynamic processes that may
      alter drug availability and target cell responsiveness with reference to
      biological time. We present an overview of the importance of time-patterned
      signals in physiology focused on the insights provided by a modeling approach. We
      first discuss examples of pulsatile intercellular communication by hormones such
      as gonadotropin-releasing hormone, and by cyclic adenosine monophosphate (cAMP)
      signals in Dictyostelium amoebae. Models based on reversible receptor
      desensitization account in both cases for the existence of optimal patterns of
      pulsatile signaling. Turning to circadian rhythms, we examine how models can be
      used to account for the response of 24h patterns to external stimuli such as
      light pulses or gene expression, and to predict how to restore the physiological
      characteristics of altered rhythms. Time-patterned treatments of cancer involve
      two distinct lines of research. The first, currently evaluated in clinical
      trials, relies on circadian chronomodulation of anticancer drugs, while the
      second, mostly based on theoretical studies, involves a resonance phenomenon with
      the cell-cycle length. We discuss the implications of modeling studies to improve
      the temporal patterning of drug administration.

PMID- 11962674
TI  - Clinical pharmacokinetics of 5-fluorouracil with consideration of
      chronopharmacokinetics.
AB  - Even though 5-fluorouracil (FU) is one of the oldest anticancer drugs, its use in
      cancer chemotherapy continues to increase. Fluorouracil is a pro-drug that
      requires intracellular activation to exert its effects. This makes it difficult
      to associate blood drug concentration with cell toxicity directly, although data
      from the literature show the existence of such a relationship. The relationship
      between FU pharmacokinetics and patient response has been explored extensively
      and reports attest a link between systemic drug exposure and response and
      survival. This has led to the concept of maximal tolerated exposure, and
      strategies to achieve this rely on pharmacokinetic follow-up and individual dose
      adjustment. More than 80% of the administered FU dose is eliminated by catabolism
      through dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme.
      Dihydropyrimidine dehydrogenase activity is found in most tissues but is highest
      in the liver. Peripheral blood mononuclear cells (PBMC) are used to monitor
      clinically DPD activity. A significant, but weak correlation between PBMC and
      liver DPD activity has been observed. The relationship between PBMC-DPD activity
      and FU systemic clearance is weak (r2 = 0.10); thus, simply determining PBMC-DPD
      is not sufficient to predict accurately FU clearance. Population pharmacokinetic
      analysis identified patient co-variables that influence FU clearance; drug
      kinetics is significantly reduced by increased age, high serum alkaline
      phosphatase, length of drug infusion, and low PBMC-DPD. Autoregulation of FU
      metabolism also is suggested; inhibition of DPD activity was observed after FU
      administration in both colorectal cancer patients and an animal model. Circadian
      rhythmicity in DPD activity is suggested from both human and animal
      investigations. In patients receiving protracted low dose 5-FU infusion, the
      circadian rhythm in FU plasma concentration peaks at 11:00h and is lowest at
      23:00h, on average. The inverse relationship observed between the circadian
      profile of FU plasma concentration and PBMC-DP activity in these same patients
      suggests a link between DPD activity and FU pharmacokinetics. The impact of the
      biological time of drug administration was also studied with short venous
      infusions; clearance was 70% greater at 13:00h than at 01:00h. Similarly, peak
      drug concentration occurred in the first half of the night in patients receiving
      constant rate 5-FU infusion for 2-5d. Several studies describe wide
      interindividual variation in the timing of the peak and trough of the 24h rhythm
      in DPD activity. The rational for FU chronomodulated therapy has been the
      circadian rhythm in host drug tolerance, which is greatest during the night time
      when the proliferation of normal target tissue is least. A randomized study of
      chronomodulated FU therapy with maximal delivery rate at 04:00h was shown clearly
      to be significantly more effective and less toxic than control flat FU therapy.
      Future research must focus on easy-to-obtain markers of specific rhythms to
      individualize the chronomodulated FU delivery.

PMID- 11962675
TI  - Chronomodulated chemotherapy and irradiation: an idea whose time has come?
AB  - The chronomodulated delivery of systemic chemotherapy given with irradiation
      (chemoradiation) is driven by an understanding of: the chronobiology of normal
      tissue response to cytotoxic insult, chronopharmacology, and by technologic
      advances in vascular access and in the availability of portable programmable
      pumps. Since circadian variation exists in the proliferative activity of acute
      reacting normal tissues like the gut and bone marrow, a potential therapeutic
      gain can be realized by the chronomodulated administration of S-phase
      chemotherapeutic agents at biological times when these normal tissues are in a
      different cell phase and thus relatively spared (chronotolerance). The reasons
      for this are complex and possibly include newly described time-keeping genes that
      may influence the cell cycle. Another important aspect of chronotolerance is
      based on chronopharmacologic behavior of S-phase chemotherapeutic radiation
      sensitizing agents, especially 5-fluorouracil (5-FU). In this review laboratory
      and clinical evidence is presented for using chronomodulated 5-FU or the
      topoisomerase-I inhibitor, camptothecin, when best tolerated biologically.
      Although the main body of this work has been accomplished with pure chemotherapy
      schedules, there is emerging clinical evidence this approach to treatment also
      applies to the application of chemoradiation. This knowledge has been exploited
      only recently in the clinic. These data should be viewed as a call for additional
      studies to investigate the precise timing of systemic chemotherapeutic radio
      sensitizers to ameliorate toxicity and maximize treatment effect, especially with
      newer and potentially more toxic chemoradiation programs.

PMID- 11962676
TI  - Chronotherapy of colorectal cancer.
AB  - Chronotherapy consists of chemotherapy delivery according to circadian rhythms.
      These genetically based rhythms modulate cellular metabolism and cell
      proliferation in normal tissues. As a result, both the host tolerance and
      antitumor efficacy of 5-fluorouracil (5-FU) and oxaliplatin (L-OHP), like 30
      other anticancer drugs, vary largely according to the dosing time in laboratory
      rodents. The transfer of this concept to the clinic is aimed primarily at
      increasing the dose-intensity of the therapy through adjustment of drug-delivery
      to 24h rhythms in host tolerance. A specific technology (programmable-in-time
      infusion pumps) enables administration of chronotherapy to fully ambulatory
      patients. Phase I-III clinical trials show chronotherapy significantly increases
      tolerance to high doses of cancer drugs and improves antitumor activity in
      patients with metastatic colorectal cancer. These safe conditions of drug
      delivery led to the first demonstration of the high activity of the 5-FU
      leucovorin-L-OHP protocol. Chronotherapy with these three drugs also allows
      surgical removal of previously unresectable liver and lung metastases. This novel
      medico-surgical management provides hope for the cure of metastatic disease in
      patients with unresectable colorectal cancer metastases.

PMID- 11962677
TI  - Tumor-based rhythms of anticancer efficacy in experimental models.
AB  - Experimental tumor models constitute a prerequisite toward chronotherapy testing
      in cancer patients. Studies in experimental models are required to understand the
      relation between tumor rhythms and antitumor treatments efficacy. In healthy
      tissues, cell proliferation, and differentiation processes are regulated
      precisely and exhibit marked circadian rhythmicity. Experimental and human tumors
      can retain circadian rhythms or display altered oscillations. Healthy tissues can
      also display rhythm modifications, possibly related to cancer stage. Cellular
      rhythms modulate the metabolism of cytotoxic agents and the cellular response to
      them; hence, they determine the chronopharmacology of anticancer drugs. Circadian
      rhythms in host tolerability and/or cancer chemotherapy efficacy have been
      demonstrated with nontoxic doses of drugs in several experimental tumor models,
      while in other ones a circadian-time effect was only seen within a specific dose
      range. The usual coupling between tolerability and efficacy rhythms of anticancer
      agents has resulted in significant improvement of their therapeutic index.
      Results of laboratory animal studies have been extrapolated to the design of
      clinical cancer therapy trials involving a chronobiological approach.

PMID- 11962678
TI  - Circadian concepts in normal and neoplastic breast.
AB  - Normal breast exhibits rhythmic properties linked to the hormonal environment of
      the gland in animals and humans. Breast tumors also display rhythmic properties;
      however, they differ from those found normally in animals and humans. Breast
      cancer in humans is characterized by disruption or modification of normal
      circadian patterns, which may be of prognostic value. The relationships between
      melatonin biology and breast cancer require exploration. The present work
      summarizes the data concerning circadian concepts in breast cancer and explores
      future directions in the breast cancer treatment by chronomodulation of
      medications during the 24h, taking advantage of the circadian time structure of
      breast tissue to improve the treatment outcome.

PMID- 11962679
TI  - Circadian chemotherapy for gynecological and genitourinary cancers.
AB  - The circadian timing of surgery, anticancer drugs, radiation therapy, and
      biologic agents can result in improved toxicity profiles, tumor control, and host
      survival. Optimally timed cancer chemotherapy with doxorubicin or pirarubicin
      (06:00h) and cisplatin (18:00h) enhanced the control of advanced ovarian cancer
      while minimizing side effects, and increased the response rate in metastatic
      endometrial cancer. Therapy of metastatic bladder cancer with doxorubicin
      cisplatin was made more tolerable by this same circadian approach resulting in a
      57% objective response rate. This optimally timed therapy is also effective in
      the adjuvant setting, decreasing the expected frequency of metastasis from
      locally advanced bladder cancer. Circadian fluorodeoxyuridine (FUDR) continuous
      infusion (70% of the daily dose given between 15:00h and 21:00h) has been shown
      effective for metastatic renal cell carcinoma resulting in 29% objective response
      and stable disease of more than 1 yr duration in the majority of patients.
      Toxicity is reduced markedly when FUDR infusion is modulated to circadian
      rhythms. In a multicenter trial in patients with metastatic renal cell cancer,
      patients were randomized to a flat or a circadian-modified FUDR infusion. This
      study confirmed a significant difference in toxicity and dose intensity, favoring
      the circadian-modified group. Hormone refractory metastatic prostate cancer has
      been treated with circadian-timed FUDR chemotherapy; however, without objective
      response. Biological agents such as interferon-alpha and IL-2 have shown low but
      effective disease control in metastatic renal cell cancer, however, with much
      toxicity. Each of these cytokines shows circadian stage dependent toxicity and
      efficacy in model systems. In summary, the timing of anthracycline, platinum, and
      fluoropyrimidine-based drug therapies during the 24h is relevant to the toxic
      therapeutic ratio of these agents in the treatment of gynecologic and
      genitourinary cancers.

PMID- 11962681
TI  - Chronomodulated chemotherapy: clinical value and possibilities for dissemination
      in the United States.
AB  - Modern medicine has been relatively slow to apply chronotherapeutic principles to
      standard oncologic practice. Despite the impressive body of evidence supporting
      the use of chronochemotherapy, with only a rare exception most oncology clinics
      in the United States lack the expertise and capability to implement it. At the
      same time, American medicine has increasingly come to recognize the importance of
      toxicity mitigation, cytoprotection, and quality of life for patients undergoing
      cancer treatment. However, toxicity mitigation strategies such as chronomodulated
      infusional chemotherapy and novel cytoprotective agents are not widely embraced
      by U.S. physicians. This article explores some reasons why this situation exists,
      including the influence of non-medical biases that may affect management
      decisions on the application of chemotherapy. The author conducted a survey of
      U.S. companies representing the three private insurance payers available (HMO,
      PPO, Indemnity) as well as representatives of Medicare and Medicaid. Responses to
      the survey confirmed that U.S. insurers do not at present officially reimburse
      for chronotherapy; however, changes will come about through educational efforts
      aimed at increasing awareness among insurers as to the clinical benefits and cost
      effectiveness of this mode of treatment. At this juncture, the outlook for cancer
      chronotherapy as a first-line approach to the treatment of metastatic cancer in
      the United States remains uncertain. Under the current method of insurance
      reimbursement, the advancement of chronotherapy in the United States is
      threatened despite evidence that such treatment is both therapeutically sound and
      cost-effective.

PMID- 11962680
TI  - Chronobiological concepts underlying the chronotherapy of human lung cancer.
AB  - This article reviews the experimental and clinical data that form the basis for
      the chronotherapy of lung carcinoma, specifically, nonsmall cell lung cancer
      (NSCLC). Circadian rhythms in cell kinetics, immunological and endocrinological
      endpoints, and tumor markers are reviewed. Chronopharmacology and chronotolerance
      studies on laboratory animals and clinical observations on cancer patients
      involving the main drugs active in lung carcinoma have prompted prospective Phase
      I-III studies to evaluate the application of chronobiologic concepts in the
      treatment of NSCLC. Circadian rhythmicity in host tolerance (chronotolerance) to
      medications has been confirmed in two prospective randomized lung cancer trials;
      a large phase II study has established the value of chronobiologic concepts to
      improve the therapeutic index of advanced NSCLC.

PMID- 11962682
TI  - Pharmaco-economic comparative evaluation of combination chronotherapy vs.
      standard chemotherapy for colorectal cancer.
AB  - Results of recent trials comparing combination chemotherapy consisting of 5
      fluorouracil (5-FU), folinic acid (FOL), and oxaliplatin, given either as flat
      (A) or chronomodulated (B) infusion for metastatic colorectal cancer, were
      subjected to pharmaco-economic evaluation. The overall cost of treatment with the
      flat and chronomodulated protocols was equivalent. The expense of the delivery of
      medications with the chronotherapeutic arm (B) was greater than with the standard
      arm (A) because it was feasible to administer more courses (requiring more
      frequent doctor visits) and higher doses (high cost of medications) with
      containment of toxic reactions. Chrono-arm B was definitively more cost-effective
      than standard flat-arm A treatment since it made the outcome of treatment more
      effective; there was greater tumor response rate and longer time to progression
      with less treatment-associated toxicity. Finally, selection of the Melodie brand
      infusion pump to deliver the chronotherapy resulted in a further 18% reduction of
      overall costs and made it possible for patients to enjoy increased autonomy and
      improved quality of life.

PMID- 11962683
TI  - Quality of life and chronotherapy.
AB  - The importance of evaluating patient's quality of life (QoL) in clinical practice
      and research is recognized clearly in oncology. In the advanced phase of disease
      such an evaluation represents an endpoint as important as survival. Quality of
      life is both a subjective and multidimensional concept evaluated mainly by
      validated questionnaires. In colorectal trials involving advanced stage disease
      the effects of different chemotherapy treatments on QoL were evaluated. Almost
      all the studies found no deterioration in QoL during chemotherapy. The European
      Organization for the Research and Treatment of Cancer (EORTC) Chronotherapy Study
      Group utilized three different approaches to assess QoL. The first centered on
      the stability of QoL during a 6mon treatment period in patients undergoing
      chronotherapy. The second centered on research of the biological and clinical
      determinants of QoL involving features of the circadian activity rhythm and
      patient survival and the relationship between QoL and patient performance status,
      response to therapy, and psychosocial variables as well as drug-induced toxicity.
      The third centered on the clinical effectiveness of psychological intervention on
      patients undergoing chronotherapy to improve psychosocial status during
      treatment. This papers reviews the results of EORTC Chronotherapy Group studies
      on QoL.

PMID- 11962684
TI  - Contribution of the rest-activity circadian rhythm to quality of life in cancer
      patients.
AB  - Quality of life (QoL) is estimated from patients scores to items related to
      everyday life, including rest and activity. The rest-activity rhythm reflects
      endogenous circadian clock function. The relation between the individual rhythm
      in activity and QoL was investigated in 200 patients with metastatic colorectal
      cancer. Patients wore a wrist actigraph (Ambulatory Monitoring Inc., New York.
      NY) for 3-5 d before chronotherapy, and completed a QoL questionnaire developed
      by the European Organization for Research and Treatment of Cancer (QLQ-C30) plus
      the Hospital Anxiety and Depression Scale. The rest-activity circadian rhythm was
      characterized by the mean activity level (m), autocorrelation coefficient at 24h
      (r24), and the dichotomy index (I < O). a ratio between the amount of activity
      while in and out of bed. The distribution of the rest-activity cycle parameters
      and that of QoL scores was independent of sex, age, primary tumor, number of
      metastatic sites, and prior treatment. Both the 24h rhythm indicators were
      positively correlated with global QoL score as well as physical, emotional, and
      social functioning. Negative correlations were found between m, r24, or I < O and
      fatigue, appetite loss, and nausea. The rest-activity circadian rhythm appeared
      to be an objective indicator of physical welfare and QoL. This analysis suggests
      that circadian function may be one of the biological determinants of QoL in
      cancer patients.

PMID- 11962685
TI  - Pharmacological effects of vinorelbine on body temperature and locomotor activity
      circadian rhythms in mice.
AB  - The effects of vinorelbine (VRL) on the circadian rhythms in body temperature and
      locomotor activity were investigated in unrestrained B6D2F1 mice implanted with
      radio-telemetry transmitters. A single intravenous VRL dose (24 or 12 mg/kg) was
      given at 7 h after light onset (HALO), a time of high VRL toxicity, and resulted
      in transient suppression of temperature and activity circadian rhythms in mice
      kept in light-dark (LD) 12h: 12h. Such suppression was dose-dependent. It
      occurred within 1-5 d after VRL dosing. Recovery of both rhythms was partially
      complete within 5 d following the high dose and within 2 or 3 d after the low
      dose and was not influenced by suppression of photoperiodic synchronization by
      housing in continuous darkness. Moreover, VRL induced a dose-dependent relative
      decrease in amplitude and phase shift of the temperature circadian rhythm. The
      mesor and amplitude of the activity rhythm were markedly reduced following the
      VRL administration. The relevance of VRL dosing time was studied in mice housed
      in LD 12h:12h. Vinorelbine was injected weekly (20 mg/kg/injection) for 3 wk at 6
      or 18 HALO. Vinorelbine treatment ablated the rest-activity and temperature
      rhythms 3-6d after each dose, with fewer alterations after VRL dosing at 18 HALO
      compared to 6 HALO, especially for the body temperature rhythm. There was at
      least partial recovery 1 wk after dosing, suggesting the weekly schedule of drug
      treatment is acceptable for therapeutic purposes. Our findings demonstrate that
      VRL can transiently, yet profoundly, alter circadian clock function. Vinorelbine
      induced circadian dysfunction may contribute to the toxicokinetics of this and
      possibly other anticancer drugs.

PMID- 11962687
TI  - Circadian rhythms of DNA synthesis in nasopharyngeal carcinoma cells.
AB  - Nasopharyngeal carcinoma (NPC) occurs frequently in southern China. The circadian
      rhythm of DNA synthesis of a poorly differentiated NPC human cell line (CNE2) was
      investigated as an experimental prerequisite for designing chrono-chemotherapy
      schedules for patients with this disease. Twenty-two nude mice with BALB/c
      background were synchronized alternatively in 12h of light and 12h of darkness
      (LD12:12) for at least 3wk prior to the transplantation of a CNE2 tumor fragment
      into each flank (area of approximately 2 x 2 mm2). Ten days later, a tumor sample
      (area of approximately 5 mm2) was obtained at 3, 9, 15, and 21 h after light
      onset (HALO) alternatively from different sites in each mouse. Single-cell
      suspensions were prepared and stained with propidium iodide. Cellular DNA content
      was measured with flow cytometry. Data were analyzed by ANOVA and cosinor
      methods. The average proportion of tumor cells in G1, S or G2-M phase varied
      according to circadian time with statistical significance. The maximum occurred
      at 9 HALO for G1, 2 HALO for S and 21 HALO for G2-M phase cells. The approximate
      average distribution patterns of G1 and G2-M phases of cosine curve was 24 h.
      This was not the case for S-phase cells, which displayed a bimodal temporal
      pattern. Inter-individual variability in peak time was large, possibly due to
      relatively sparse sampling time. Nevertheless, no more than 6% of the time series
      displayed a maximum at 3 HALO for G1, 21 HALO for S and 15 HALO for G2-M. The
      cell cycle distribution of this human NPC cell line displayed circadian
      regulation following implantation into nude mice. The mechanisms involved in this
      rhythm and its relevance to the chrono-chemotherapy of patients deserve further
      investigation.

PMID- 11962686
TI  - In-vitro circadian rhythm of murine bone marrow progenitor production.
AB  - Hematopoietic processes display 24h rhythms both in rodents and in human beings.
      We hypothesized these rhythms to be in part generated by a circadian oscillator
      within the bone marrow. The ability of murine bone marrow granulo-monocytic (GM)
      precursors to form colonies following colony-stimulating factor (rm GM-CSF)
      exposure was investigated in liquid culture samples obtained every 3 h for a span
      of up to 198 h. The CFU-GM count varied rhythmically over the first 4 d of
      culture, with a reproducible maximum in the early morning hours, similar to that
      observed in vivo. These experiments provide the first evidence that bone marrow
      progenitors sustain in vitro circadian rhythmicity, and they demonstrate the
      presence of a circadian time-keeping system within these cells. The results
      support the potential usefulness of bone marrow cultures for investigating
      chronopharmacologic effects of anticancer drugs and cytokines on this target
      system.

PMID- 11962688
TI  - Chronobiology of the mammalian response to ionizing radiation. Potential
      applications in oncology.
AB  - Ionizing radiation from all sources under appropriate conditions leads to cell
      death and tissue damage. It is used in cancer treatment under the assumption of a
      higher radiosensitivity of the fast dividing tumor cells as compared with
      adjacent host tissues. The radiosensitivities of proliferating host tissues like
      bone marrow and gastrointestinal lining epithelium are dose limiting. Since these
      host tissues and many tumors show circadian and other periodicities in their cell
      proliferation, the timing of radiation treatment according to host and/or tumor
      rhythms is expected to improve the toxic/therapeutic ratio of the treatment. The
      experimental data on the chronobiology of radiation exposure show circadian
      rhythmicity in radiation response after whole body irradiation in mice and rats
      with highest toxicity in light-dark 12h:12h synchronized animals during their
      daily activity span. Bone marrow toxicity as well as gastrointestinal epithelial
      damage show circadian rhythms in part due to radiation damage to the stem cells
      involved and especially in the intestine also due to damage to the
      microvasculature. Chronoradiotherapy of malignant tumors seems promising, alone
      or in combination with response modifiers, provided the host and potential tumor
      rhythms can be monitored.

PMID- 11962689
TI  - Toxicological studies on Polyporus pinsitus laccase expressed by Aspergillus
      oryzae intended for use in food.
AB  - The laccase used in the study was produced by submerged fermentation of
      Aspergillus oryzae, containing a gene originating from Polyporus pinsitus.
      Laccase is to be employed as a processing aid in the juice industry to make a
      clear and stable juice. The enzyme was subject to a series of toxicological tests
      to document its safety in use. It was not mutagenic in the Salmonella typhimurium
      reverse mutation assay, and it did not cause chromosomal aberrations in cultured
      human lymphocytes. No evidence of inhalation toxicity or skin and eye irritation
      was found. Oral administration to rat of up to 10 ml kg(-1) b.w. day(-1)
      (equivalent to a total organic solids dosage of 676 mg kg(-1) b.w. day(-1) or a
      laccase dosage of 2601 LACU kg(-1) b.w. day(-1)) for 13 weeks did not cause any
      adverse effect. The maximum recommended dosage of laccase used for juice
      applications is 50 LACU l(-1) juice.

PMID- 11962690
TI  - Survey of residual solvents in natural food additives by standard addition head
      space GC.
AB  - Residual levels of 12 solvents in 87 natural food additives (66 samples of food
      colours, 19 samples of natural antioxidants and two natural preservatives)
      collected between 1997 and 1999 were determined by automated head-space GC using
      FID, with a porous-polymer (PLOT) column. Calibration curves were prepared by the
      method of standard addition. Confirmation was by manually injected head-space GC
      using mass spectrometric detection. 1,2-Dichloroethane was found in turmeric
      colour (natural food colour) collected in 1997 at the concentrations of 8.6
      microg g(-1), but was not found in samples collected in 1998 and 1999. Hexane was
      found in three samples of dunaliella carotene (11, 72 and 75 microg g(-1)), and
      in chlorophyll at 93 microg g(-1) (both natural food colours). Acetone was found
      in turmeric colour, annatto colour, dunaliella carotene, kaoliang colour, cacao
      colour at a concentration between 8.7 and 42 microg g(-1) (all natural food
      colours).

PMID- 11962691
TI  - Determination of 1,3-dichloropropanol in soy sauces by automated headspace gas
      chromatography-mass spectrometry.
AB  - There has been recent concern about the levels of carcinogenic chloropropanols in
      some soy sauces. We have devised and tested a new automated headspace GC-MS
      technique for the analysis of 1,3-dichloropropan-2-ol (1,3-DCP) in soy sauce and
      similar products. The method incorporates the use of cryogenic trapping and a
      deuterium-labelled internal standard. The limit of detection was 0.003 mg kg(-1).
      After in-house validation testing, the method was applied to soy sauce samples
      that had previously been analysed for the related contaminant 3
      monochloropropanediol (3-MCPD). 1,3-DCP was detected in 10 of 40 sauces, all of
      which also contained 3-MCPD. The highest level was just >1 mg kg(-1). There was
      no correlation between the levels of 1,3-DCP and 3-MCPD.

PMID- 11962692
TI  - Lack of mutagenicity of a red food colour impurity (1-carboxyl-5,7-dibromo-6
      hydroxy-2,3,4-trichloroxanthone) in phloxine B.
AB  - To evaluate the mutagenicity of 1-carboxyl-5,7-dibromo-6-hydroxy-2,3,4
      trichloroxanthone (HXCA), which is an impurity present in Food Red No. 104
      (FR104, Phloxine B, the Japanese counterpart of D&C Red No. 28), HXCA was
      isolatedfrom FR104 using pH-zone-refining counter-current chromatography and
      preparative HPLC. A large amount of HXCA was synthesized to perform the Ames
      test, and its identity was confirmed by comparison of its HPLC retention time, UV
      Vis, MS and NMR spectra with those of HXCA isolated from FR104. The results of
      the Ames test using synthetic HXCA showed that it did not possess mutagenic
      activity. The results of the mutagenicity test for HXCA will provide useful
      information for the establishment of an upper limit for HXCA in FR104 (or D&C Red
      No. 28) for use in regulatory considerations.

PMID- 11962693
TI  - Analysis and monitoring of chloramphenicol residues in food of animal origin in
      Slovenia from 1991 to 2000.
AB  - To prevent the illegal use of chloramphenicol (CAP), regulatory control of its
      residues in food of animal origin is essential. In Slovenia, the monitoring of
      CAP residues for statutory purpose started in 1991. The results of a 10-year
      period are presented. CAP residues were determined by capillary gas
      chromatography (GC) with electron capture detection (ECD) using meta-CAP as an
      internal standard (ISTD). Before chromatographic determination, analytes were
      derivatized by silylation. Overall, CAP recovery, adjusted for ISTD, was for
      bovine muscle tissue and raw cow's milk (in the region of 2-10 microg kg(-1)) 89
      and 102%, respectively, and for whole eggs, 87% (in the region of 1-10 microg kg(
      1)). The use of meta-CAP improved significantly the precision of the method. The
      detection limit for CAP was 1 microg kg(-1), which was sufficiently sensitive for
      routine use. A total of 1308 random samples of Slovenian origin were analysed
      from 1991 to 2000, covering all parts of the country. CAP was found only in one
      milk sample in 1997 at a concentration of 4.6 microg kg(-1).

PMID- 11962694
TI  - Transfer and distribution profiles of dietary sulphonamides in the tissues of the
      laying hen.
AB  - The five sulphonamides, sulphadiazine (SDZ), sulphadimidine (SDD),
      sulphamethoxazole (SMX), sulphamonomethoxine (SMM) and sulphaquinoxaline (SQ),
      were fed to laying hens at a dietary concentration of 100 mg kg(-1),
      respectively. On the 7th day after the start of feeding, the drug concentrations
      in the plasma, muscle and the main tissues involved in egg formation, the liver,
      and ovary and oviducts (magnum and isthmus plus shell grand) were determined by
      high-performance liquid chromatography. Dietary sulphonamides were distributed
      throughout the above tissues. SQ was found at the highest concentration in all
      tissues, while the reverse was true for SDD. The ratio of SDD concentrations in
      the main tissues involved in egg formation to that in the plasma were greater
      than those for the other drugs.

PMID- 11962696
TI  - Structural characterization of metabolites after the microbial degradation of
      type A trichothecenes by the bacterial strain BBSH 797.
AB  - Contamination of feed with trichothecenes, a group of Fusarium mycotoxins, leads
      to losses in performance due to their immunosupressive effects and the negative
      effect on the gastrointestinal system in animal production. A possible way of
      detoxification is microbial degradation, which was the focus of this study. A
      bacterial strain--BBSH 797--which can degrade some mycotoxins of the
      trichothecene group, has already been isolated. It transforms deoxynivalenol
      (DON) into its metabolite DOM-1, the non-toxic deepoxide of DON. Analogous to the
      microbial degradation of DON, the transformation of six different type A
      trichothecenes was observed. The metabolites appearing were characterized by GC
      MS after derivatization with TRI-SIL TBT. Two metabolites were additionally,
      identified by liquid chromatography-mass spectrometry with particle beam
      interface (LC-PB-MS) with electron impact (EI)-ionization mode. The major finding
      was that scirpentriol was completely transformed into its non-toxic metabolite
      deepoxy scirpentriol, while the mycotoxin T-2 triol underwent a more complicated
      metabolism. According to the study, T-2-triol was degraded into its non-toxic
      deepoxy form and into T-2 tetraol, which was then further metabolized to deepoxy
      T-2 tetraol. GC-MS after derivatization with TRI-SIL TBT was suitable for the
      structural characterization of trichothecenes and their degradation products.
      Besides the mass spectra of already known degradation products, spectra of new
      metabolites could be recorded by LC-PB-MS.

PMID- 11962695
TI  - Sulphonamide residues in eggs following drug administration via the drinking
      water.
AB  - The aim was to determine concentrations of sulphadimidine (SDM) and
      sulphadimethoxine (SDT) in eggs following oral administration through drinking
      water for 5 days (0.5 g l(-1) for SDT, 1 and 2 g l(-1) for SDM). Residues of
      sulphonamides in albumen and yolk were monitored by high-performance liquid
      chromatography with UV detection. The limit of quantification was 0.005 microg g(
      1) for the two egg components. The results indicate that 0.9-1.4% of the dose
      administered was deposited in eggs. Maximum concentrations in albumen were much
      higher than those in yolk. More than 75% of the overall sulphonamides detected in
      eggs was concentrated in the albumen. The residue levels declined below the limit
      of quantification within 12-20 days for albumen and 14-15 days for yolk after
      treatment was discontinued.

PMID- 11962697
TI  - Fate of patulin in the presence of the yeast Saccharomyces cerevisiae.
AB  - Patulin is known to become analytically non-detectable during the production of
      cider from contaminated apple juice. The fate of [14C]-labelled patulin during
      the alcoholic fermentation of apple juice was studied. Three commercial cider
      strains of Saccharomyces cerevisiae degraded patulin during active fermentative
      growth, but not when growing aerobically. The products of patulin degradation
      were more polar than patulin itself and remained in the clarified fermented
      cider. Patulin did not appear to bind to yeast cells or apple juice sediment in
      these model experiments. HPLC analysis of patulin-spiked fermentations showed the
      appearance of two major metabolites, one of which corresponded by both TLC and
      HPLC to E-ascladiol prepared by the chemical reduction of patulin using sodium
      borohydride. Using a diode array detector, both metabolites had a lambda(max) =
      271 nm, identical to that of ascladiol. The nmr spectrum of a crude preparation
      of these metabolites showed signals corresponding to those of the E-ascladiol
      prepared chemically and a weaker set of signals corresponding to those reported
      in the literature for Z-ascladiol.

PMID- 11962698
TI  - Fluorescence polarization as a tool for the determination of deoxynivalenol in
      wheat.
AB  - The mould Fusarium graminearum is found worldwide as a pathogen of cereal grains,
      in particular of wheat and maize, and it produces a mycotoxin known as
      deoxynivalenol (DON or vomitoxin). Each year, the presence of this compound and
      related trichothecenes causes substantial losses to agricultural productivity.
      Rapid methods for the measurement of the toxin in grains are required to monitor
      and divert effectively contaminated grain from the food supply. A fluorescence
      polarization (FP) immunoassay using a previously described monoclonal antibody
      for DON was developed. The assay was based on the competition of unlabeled DON
      from a sample with a fluorescently tagged DON, DON-fluorescein (DON-FL), for a
      DON-specific monoclonal antibody in solution. The FP of the tagged DON was
      increased upon binding with the antibody. In the presence of free toxin, less of
      the DON-FL was bound and the polarization signal was decreased. The assays were
      very simple to perform, requiring only mixing of an aqueous extract of wheat with
      the DON-FL and antibody. The sensitivity of the assay was strongly dependent upon
      the time between mixing of the sample with the tracer and measurement of the
      fluorescence polarization, with midpoints for the competition curves ranging from
      0.03 microg ml(-1) with a 15-s incubation to >1 microg ml(-1) with a 12-min
      incubation. Samples of wheat naturally contaminated with DON were evaluated by FP
      and by an HPLC-UV method, with a good correlation (r2 = 0.97). Although the FP
      method tended to overestimate DON slightly in the wheat samples, by approxiamtely
      20%, the assay was easy to use and very useful for the screening of wheat.

PMID- 11962699
TI  - Potential ochratoxin A producers from wine grapes in Argentina and Brazil.
AB  - The aim was to identify the normal mycoflora in wine grapes from Argentina and
      Brazil. We collected 50 grapes samples from Malbec and Chardonnay varieties in
      each country during the 1997-98 harvest. Yeasts were a major component of the
      fungal population, and the most frequent genera of filamentous fungi isolated
      were: Aspergillus, Penicillium and Botrytis. Other genera identified (in
      decreasing order) were: Phythophthora, Moniliella, Alternaria and Cladosporium.
      From grapes, the mean frequency of filamentous fungi ranged from 1.3 x 10(4) to
      5.4 x 10(6) CFU g(-1). We isolated 48 Aspergillus niger strains from Argentinian
      grape, of which eight could produce ochratoxin A. Sixteen of 53 A. niger strains
      from Brazilian grapes produced ochratoxin A. The results indicate that similar
      mycobiota were isolated from Argentinian and Brazilian wine grapes and there
      could be ochratoxin A production in this substrate.

PMID- 11962700
TI  - Polyethylene terephthalate recycling for food-contact applications: testing,
      safety and technologies: a global perspective.
AB  - Studies were undertaken to determine the composition of five different types of
      post-consumer polyethylene terephthalate (PET) feedstreams to ascertain the
      relative amounts of food containers and non-food containers. Deposit post
      consumer PET feedstreams contained approximately 100% food containers, whereas
      curbside feedstreams contained from 0.04 to 6% non-food containers. Analysis of
      the PET containers from the different type feedstreams after the containers were
      subjected to a commercial PET wash system and after processing with a proprietary
      decontamination technology was accomplished to determine the levels of compounds
      in the post-consumer PET after the various stages of processing. Comprehensive
      thermal desorption/GC/MS, purge and trap GC/MS purge and trap GC quantitation,
      PET dissolution and extraction GC analysis and PET dissolution HPLC analysis
      established the types and concentrations of compounds that absorb in the PET from
      the various types of postconsumer feedstreams. A total of 121 compounds were
      identified in the five different feedstreams. The concentration of absorbed
      compounds remaining in the deposit material and the non-food applications
      material after the commercial wash was 28 and 39mgkg(-1) respectively. Analysis
      of the feedstreams after subjecting the material to a proprietary decontamination
      process demonstrated the ability of removing all the absorbed compounds to a
      level below the level of the threshold of regulation. The safety of sourcing of
      post-consumer PET from food use applications verses non-food use applications of
      PET has been established.

PMID- 11962701
TI  - Toxicity testing and chemical analyses of recycled fibre-based paper for food
      contact.
AB  - Food-contact materials, including paper, have to comply with a basic set of
      criteria concerning safety. This means that paper for food contact should not
      give rise to migration of components, which can endanger human health. The
      objectives of this pilot study were, first, to compare paper of different
      qualities as food-contact materials and to perform a preliminary evaluation of
      their suitability, from a safety point of view, and, second, to evaluate the use
      of different in vitro toxicity tests for screening of paper and board. Paper
      produced from three different categories of recycled fibres (B-D) and a raw
      material produced from virgin fibres (A) were obtained from industry, and
      extracts were examined by chemical analyses and diverse in vitro toxicity test
      systems. The products tested were either based on different raw materials or
      different treatments were applied. Paper category B was made from 40% virgin
      fibres, 40% unprinted cuttings from newspapers, and 20% de-inked newspapers and
      magazines. Paper categories C and D were based on newspapers and magazines.
      However, paper D was de-inked, whereas C was not. To identify constituents of the
      papers with a potential to migrate into foodstuff, samples of the paper products
      were extracted with either 99% ethanol or water. Potential migrants in the
      extracts were identified and semiquantified by GC-IR-MS or GC-HRMS. In parallel
      to the chemical analyses, a battery of four different in vitro toxicity tests
      with different endpoints were applied to the same extracts. (1) a cytotoxicity
      test using normal human skin fibroblasts. The test was based on measurements of
      the reduction of resazurin to resorufin by cellular redox processes and used as a
      screening test for acute or general toxicity; (2) a Salmonella/microsome assay
      (Ames test) as a screening test for mutagenic and potentially carcinogenic
      compounds; (3) a recombinant yeast cell bioassay as a screening test for
      compounds with oestrogenic activity; (4) an aryl hydrocarbon (Ah)-receptor assay
      (CALUX assay) as a screening test for compounds with dioxin-like activity. In
      addition, the papers were testedfor microbial content and, in general, the
      microbiological load was quite low. The following microorganisms were counted and
      identified on both surface and homogenized pulp samples: the total number of
      aerobic bacteria, the number of aerobic and anaerobic spore formers, the number
      of Bacillus cereus/thuringiensis, and the number of yeast and moulds. The
      chemical analyses showed a significantly higher amount and different composition
      pattern of chemicals extracted with ethanol compared with water. Analyses of the
      ethanol extracts showed a distinctly smaller number and lower concentrations of
      chemicals in extracts prepared from sample A compared with extracts of samples B
      D. The compounds identified in B-D were similar, but the amounts were lower in B
      compared with C and D. In accordance with the chemical analyses, the water
      extracts were less cytotoxic than the ethanol extracts. The extract prepared from
      virgin fibres was less cytotoxic than the extracts prepared from paper made from
      recycled fibres, and extracts prepared from C was the most cytotoxic. None of the
      extracts showed mutagenic activity. No conclusion about the oestrogenic activity
      could be made, because all extracts were cytotoxic to the test organism (yeast
      cells). Ethanol extracts of A and B showed a negligible positive response in the
      Ah-receptor assay at the highest nontoxic concentration, whereas C and D showed a
      more pronounced effect with C being the most potent. A comparable weak effect of
      water extracts of samples B-D was observed, too. However, the active compound(s)
      was not identified by chemical analyses.

PMID- 11962702
TI  - Evaluating the potential for recycling all PET bottles into new food packaging.
AB  - To evaluate the feasibility of recycling all PET bottles into food packaging,
      realistic estimates of the maximum concentration of contaminants that might be
      expected in the polymer are needed. To estimate the maximum concentration of a
      contaminant that might be in PET from the storage of non-food substances,
      sorption experiments into two types of PET were performed. These test materials
      were 0.8mm thick amorphous PET (a relative sink for contaminants) and commercial
      PET bottle wall. Using a commercial shampoo containing 1% lindane (C6H6Cl6), the
      test materials were stored in contact with the shampoo at 20 and 40 degrees C for
      231 days. This commercial shampoo also represents an extreme case because it
      contains 7% acetone, a solvent which swells PET, further enhancing sorption of
      chemicals. Additional sorption experiments into PET were performed by preparing
      solutions of 10% toluene in Miglyol (a fractionated coconut oil), 10%
      benzophenone in Miglyol, 5% 2-butoxyethoxy ethanol (2-BE) in 50/50 water/ethanol,
      and 10% methyl stearate in heptane. Sorption data from the shampoo into PET
      illustrate Fickian behaviour. Specifically, the amount of sorption at room
      temperature is approximately40 times less than that at 40 degrees C. The amount
      of lindane sorbed into PET from the shampoo after 231 days was 0.1 and 3.7 mgdm(
      2) at 20 and 40 degrees C respectively. These values correspond to 28 and 765 mg
      kg(-1) on a mass/mass basis. All sorptions are within the ranges measured and
      published by other authors using surrogate contamination testing schemes.
      Additionally, actual bottles from recycle bins were analysed for the amout of
      contamination. Results are discussed in terms of potential consumer exposure to
      non-food contaminants in food containers made of recycled PET and in relation to
      the surrogate testing methods recommended by the Food and Drug Administration
      (FDA) for determining the compatibility of a PET recycling process to produce
      containers suitable for food-contact use.

PMID- 11962703
TI  - Active and intelligent packaging: applications and regulatory aspects.
AB  - Changes in the way foods are produced, distributed, stored and retailed,
      reflecting the continuing increase in consumer demands for improved quality and
      extended shelf-life for packaged foods, are placing ever-greater demands on the
      performance of food packaging. Consumers want to be assured that the packaging is
      fulfilling its function of protecting the integrity, quality, freshness and
      safety of foods. To provide this assurance and help improve the performance of
      the packaging, innovative active and intelligent packaging concepts are being
      developed and applied in various countries. In Europe, however, the development
      and application of active and intelligent packaging systems have been limited
      thus far. The main reasons are legislative restrictions and a lack of knowledge
      about consumer acceptance, the efficacy of such systems, and the economic and
      environmental impact they may have. Therefore, in 1999, a European study was
      started within the framework of the EU FAIR R&D programme. It aims to initiate
      amendments to European legislation for food-contact materials to establish and
      implement active and intelligent systems within the current relevant regulations
      for packaged food in Europe. This paper presents an overview of existing active
      and intelligent systems and their current and future food-related applications.
      In addition, developments and trends in active and intelligent food packaging are
      discussed. The objectives and the work programme of the European project are
      reviewed and the results obtained so far are presented. The benefits for both the
      European consumer and the European food and food-packaging industries are
      highlighted.

PMID- 11962704
TI  - Effectiveness of some recent antimicrobial packaging concepts.
AB  - A new type of active packaging is the combination of food-packaging materials
      with antimicrobial substances to control microbial surface contamination of
      foods. For both migrating and non-migrating antimicrobial materials, intensive
      contact between the food product and packaging material is required and therefore
      potential food applications include especially vacuum or skin-packaged products,
      e.g. vacuum-packaged meat, fish, poultry or cheese. Several antimicrobial
      compounds have been combined with different types of carriers (plastic and rubber
      articles, paper-based materials, textile fibrils and food-packaging materials).
      Until now, however, few antimicrobial concepts have found applications as a food
      packaging material. Antimicrobial packaging materials cannot legally be used in
      the EU at the moment. The potential use would require amendments of several
      different legal texts involving areas such as food additives, food packaging,
      hygiene, etc. The main objective of this paper is to provide a state of the art
      about the different types of antimicrobial concepts, their experimental
      development and commercialization, and to present a case study summarizing the
      results of investigations on the feasibility of a low-density polyethylene (LDPE)
      film containing triclosan to inhibit microbial growth on food surfaces and
      consequently prolong shelf-life or improve microbial food safety. In contrast
      with the strong antimicrobial effect in in-vitro simulated vacuum-packaged
      conditions against the psychrotrophic food pathogen L. monocytogenes, the 1000 mg
      kg(-1) containing triclosan film did not effectively reduce spoilage bacteria and
      growth of L. monocytogenes on refrigerated vacuum-packaged chicken breasts stored
      at 7 degrees C.

PMID- 11962706
TI  - Determination of microbial contamination of plastic cups for dairy products and
      utilization of electron beam treatment for sterilization.
AB  - Packaging materials are often considered a critical control point in HACCP
      systems of food companies. Methods for the determination of the microbial
      contamination rate of plastic cups, especially for dairy products, must reliably
      detect single moulds, yeasts or coliforms. In this study, a comparison of a
      specially adapted coating method, impedance method, direct inoculation and
      membrane filter technique was carried out to determine contamination with yeasts,
      moulds, coliforms and total bacterial counts using the appropriate agar in each
      case. The coating method is recommended for determining yeasts, moulds and
      coliforms as it allows the localization of the microorganisms as well as the
      determination of single microorganisms. For total bacterial count, a direct
      inoculation technique is proposed. The employing of simple measures in the
      production and during transport of packaging materials, such as dust-prevention
      or tight sealing in polyethylene bags, heavily reduces microbial contamination
      rates of packaging material. To reduce contamination rates further, electron beam
      irradiation was applied: plastic cups sealed in polyethylene bags were treated
      with 4-5 kGy, a dose that already leads to sterile polystyrene and polypropylene
      cups without influencing mechanical characteristics of the packaging material.

PMID- 11962705
TI  - Production and applications of biobased packaging materials for the food
      industry.
AB  - Materials based on renewable resources are being developed at an increasing rate.
      Today, the only biobased food-packaging materials used commercially on a major
      scale are based on cellulose. However, materials based on proteins, starch,
      polylactate and other renewable resources may be the food-packaging materials of
      tomorrow. The paper presents some of the different biobased materials and their
      potential as food-packaging materials.

PMID- 11962707
TI  - Comprehensive analysis of migrates from food-packaging materials: a challenge.
AB  - The premise is put forward that present European regulation of food-packaging
      materials does not provide the assessment for safety corresponding to the opinion
      of toxicologists that migrants ingested in amounts exceeding a threshold of 1.5
      microg day(-1) should be identified and toxicologically evaluated. Many
      substances that migrate (the large majority of the components migrating from can
      coatings) are neither starting point materials, nor obvious derivatives
      therefrom, and are, therefore, not covered by existing systems based on positive
      lists. Safety presupposes the comprehensive analysis of the migrating substances,
      ultimately to the limits in terms of concentration and molecular weight
      considered to he of toxicological concern. This is a new analytical challenge. In
      this paper, expected problems are discussed, leading to the conclusion that it
      will be difficult to achieve comprehensive analysis down to the concentrations
      presently considered safe, but that systematic work should start to define the
      possibilities and limitations of analytical chemistry for a migrate-oriented
      coating legislation.

PMID- 11962708
TI  - Simple method for the selection of the appropriate food simulant for the
      evaluation of a specific food/packaging interaction.
AB  - Knowledge of the extent of food/packaging interactions is essential to provide
      assurance of food quality and shelf life, especially in migration and sorption
      processes that commonly reach equilibrium during the lifetime of a commercial
      packaged foodstuff. The limits of sorption and migration must be measured in the
      presence of the specific food or an appropriate food simulant. The partition
      equilibrium of food aroma compounds between plastic films and foods or food
      simulants (K(A,P/L) has been characterized. Two polymers (LLDPE and PET), three
      organic compounds (ethyl caproate, hexanal and 2-phenylethanol), four food
      products with varying fat content (milk cream, mayonnaise, margarine and oil) and
      three simulants (ethanol 95%, n-heptane and isooctane) were selectedfor study.
      The results show the effect of the aroma compound volatility, and polarity, as
      well as its compatibility with the polymer and the food or food simulant.
      Equilibrium constants for the organic compound between the polymers and a gaseous
      phase (K(A,P/V)) as well as between the food (or food simulant) and a gaseous
      phase (K(A,L/V)) were also determined. An approach is presented to estimate
      K(A,P/V) from the binary equilibrium constants K(A,P/V) and K(A,L/V). Calculated
      results were shown to describe experimental data very well and indicated that
      compatibility between the aroma and the food or food simulant is the main
      contributing factor to the partition equilibrium describing the extent of
      food/packaging interactions. Therefore, the measurement of liquid/vapour
      equilibrium can be regarded as a powerful tool to compare the effectiveness of
      food simulants as substitutes of a particular food product and can be used as a
      guide for the selection of the appropriate simulant.

PMID- 11962709
TI  - Creation of on-line solutions in support of the dissemination of legislative and
      analytical information on food-contact materials.
AB  - To facilitate access to European Commission (EC) documentation and provide a
      public service resource of relevant information an Internet site dedicated to
      food-contact materials was created (http://cpf.jrc.it/webpack/) in 1998. The site
      contains legislative information in downloadable format, information on contacts
      for authorities and organizations in the field of food-contact materials, as well
      as information on methods for overall and specific migration. A satellite site
      (http://cpf.jrc.it/smt/) is dedicated to physicochemical and spectral information
      (FT-IR, GC-MS, NMR) as well as analytical methods on an increasing number of
      regulated substances. Many of these, as well as substances submitted for
      evaluation, are held in a centralized databank at the JRC in Ispra and aliquots
      can be made available to the public upon request. The site also recently expanded
      to provide an incentive for analytical networking between institutions by
      including information pages on current EC-funded and national projects and
      conference announcements.

PMID- 11962710
TI  - Monitoring of taints related to printed solid boards with an electronic nose.
AB  - The main objectives were to combine knowledge gathered from the electronic nose
      (EN) with traditional analytical reference methods for measuring volatile
      compounds, such as sensory and headspace methods. The impacts of different
      colouring agents on the sensory properties of packaging materials when analysed
      by EN were determined. The first step in investigations using the EN was
      optimization of sample treatment and analysis parameters for the samples. The
      best resolution was achieved at 60 degrees C in 20 min, and the effect of
      humidity on the EN sensors was confirmed. A comparison was made of three sensory
      methods for analysing taints of packaging materials. The study showed that the
      odour of the packaging itself was often not a reliable indication of the taint
      perceived in the packed foodstuff and should be regarded only as indicative.
      Taints caused by pigments of printed solid boards were analysed by EN. Twenty
      samples were studied, representing unprinted solid board, lacquered solid board,
      offset printed solid board with 14 different colours and offset printed,
      lacquered solid board with four colours. The EN succeeded in grouping these
      materials according to their colouring agents or lacquering, despite slight
      overlapping of replicates, and the results appeared to reflect at least to some
      extent the off-flavours perceived in sensory evaluation. The results of this
      study are only indicative, because the analysis of results from different sources
      or equipment requires more extensive use of statistical methods.

PMID- 11962711
TI  - Off-flavour release from packaging materials and its prevention: a foods
      company's approach.
AB  - Off-flavours in packed food are causes for consumer complaints. Often, they are
      related to packaging materials. For food companies, this represents not only
      costs related to production, but also a possible loss of brand confidence and
      market share. The origin of packaging-related off-odours are many sided. Odours
      derive from the degradation of base packaging materials and their converting
      processes, including printing, coating and lamination as well as the interaction
      between food and packaging. Many substances and groups of substances have been
      identified so far. In spite of the fact that the quality of packaging materials
      is clearly defined in the specifications (e.g. limit for residual solvents,
      standardized odour and taste transfer tests), off-flavour cases still do occur.
      This paper sets out ways of avoiding such problems, even in factories and
      laboratories which are not so well equipped. Prevention at Nestle is based on
      several pillars. For a number of years, a sensory panel at the central laboratory
      has been specialized in and trained on packaging off-favours. The panel can
      describe and identify odours and their origin. To confirm the results by
      instrumental analysis, various extraction and separation techniques are
      available, including distillation/extraction techniques and direct thermal
      desorption followed by gas chromatography coupled with mass spectroscopy and an
      olfactory sniffing port. However, this knowledge must also be present in the
      operational plants where the problem usually originates. To manage this knowledge
      transfer, two tools were introduced to build up sensory panels that can evaluate
      packaging material. First, an aroma library kit was developed that contained
      odours that are often involved in off-odour cases. For each odour, a typical
      descriptor and the chemical composition are given. Beside that, information is
      added about the occurrence. Second, a glossary, which contains descriptors for
      packaging-related off-odours, was published. This small booklet helps to unify
      the odour descriptions, especially thanks to its translation into three important
      languages. This paper describes the tools mentioned above, as well as examples
      and limitations for their application.

PMID- 11962712
TI  - Migration modelling as a tool for quality assurance of food packaging.
AB  - The current potential for the use of migration modelling for studying polyolefin
      packaging materials (low- and high-density polyethylene and polypropylene) is
      summarized and demonstrated with practical examples. For these polymers, an upper
      limit of migration into foodstuffs can be predicted with a high degree of
      statistical confidence. The only analytical information needed for modelling in
      such cases is the initial concentration of the migrant in the polymer matrix. For
      polyolefins of unknown origin or newly developed materials with new properties, a
      quick experimental method is described for obtaining the characteristic matrix
      parameter needed for migration modelling. For easy handling of both the
      experimental results and the diffusion model, user-friendly software has been
      developed. An additional aim of the described method is the determination of the
      migrant partition between polymer and food or food simulant and the specific
      contribution of the migrant molecular structure on the diffusion coefficient. For
      migration modelling of packaging materials with multilayer structures, a
      numerical solution of the diffusion equation is described. This procedure has
      been also applied for modelling the migration into solid or high viscous
      foodstuffs.

PMID- 11962713
TI  - Risk assessment of packaging materials.
AB  - Risk assessment of packaging materials provides a unique challenge. Human
      exposure to packaging materials and/or their components occurs from migration
      into foods. There are various methods for determining migration into foods.
      Unlike most food additives, these exposures typically are very small. Because of
      this, and since complete toxicological data sets are not always available for
      packaging materials, the US Food and Drug Administration (FDA) has developed a
      process to make the evaluation of packaging materials more efficient, instead of
      the extensive review normally required for food additives. This process is used
      to determine 'when the likelihood or extent of migration to food of a substance
      used in a food-contact article is so trivial as not to require regulation of the
      substance as a food additive'. This trivial level, also known as the threshold of
      regulation, was based upon a large database of carcinogenic potencies and was
      determined to be 1.5 microg/person day(-1). This was determined to 'be low enough
      to ensure that the public health is protected, even in the event that a substance
      exempted from regulation as a food additive is later found to be a carcinogen'.
      Substances not having structural alerts, or that are not known carcinogens or
      potent toxins, based on existing toxicological information, and are below the
      threshold value, are considered by the FDA to be exempted from regulation as food
      additives. The threshold of regulation approach used by the FDA provides an
      excellent model by which to evaluate the majority of packaging materials.

PMID- 11962715
TI  - Diffusion of volatile compounds in fibre networks: experiments and modelling by
      random walk simulation.
AB  - Predictive migration models for polymers are already so well established that the
      European Commission intends to allow the use of the models as one quality
      assurance tool in product safety assessment of plastic materials and articles for
      food contact. The inhomogeneity of fibre-based materials makes modelling
      difficult--thus, little research has been done in this area. The authors compare
      experiments on the diffusion of certain volatile compounds through laboratory
      kraft pulp sheets with computer simulations in which the fibre network structure
      is modelled explicitly. The major advantage of the present random walk simulation
      is that it gives an estimate of the effective diffusion constant for the fibre
      network. For most compounds, the agreement between the experiments and
      simulations is good. The experiments and simulations indicate that gas diffusion
      rate is very sensitive to sheet porosity.

PMID- 11962714
TI  - Integrated approach of migration prediction using numerical modelling associated
      to experimental determination of key parameters.
AB  - The principle of utilizing a computing program describing precisely the migration
      of additives from a polymer into a food simulant is presented. The model has been
      validated with a UV absorber in polypropylene migrating into glyceryl
      tripelargonate, a pure triglyceride whose behaviour and average molecular weight
      are similar to Myglyol (a synthetic mixture of C8-C12 triglycerides). Six
      parameters were used to fit the simulant sorption and additive extraction
      kinetics, and these were determined by independent experiments. The possibility
      of eliminating any of the parameters is also discussed. This work provides the
      first consistent set of experimental data that can be used to overestimate the
      diffusion coefficients of additives both in virgin (without contact with solvent)
      and in swollen (fat contact) polymer. The influence of mobility increase brought
      out by temperature or swelling are compared. The effects were more important for
      high molecular weight compounds.

PMID- 11962716
TI  - Practical experience in the use of mathematical models to predict migration of
      additives from food-contact polymers.
AB  - To reduce the amount of compliance-specific migration testing for food-contact
      polymers, the use of migration modelling has been evaluated. The paper describes
      experimental work carried out on a range of plastics and compares measured
      migrations against predictions obtained using mathematical models. A large number
      of experimental migration data have been obtained and used to evaluate a Fickian
      based migration model in the prediction of specific migration of additives into
      olive oil. All tests were conducted using olive oil, representing the most severe
      case for fatty foods with test conditions including 2h at 121 degrees C, 6h at 70
      degrees C, 2h at 70 degrees C, 2h at 60 degrees C and 10 days at 40 degrees C,
      representing short-term exposures at high temperatures and room temperature
      storage. Predicted migrations were calculated by inputting the measured initial
      concentration of additive in the polymers (Cp,0) into the equations together with
      known variables such as additive molecular weight, temperature and exposure time.
      The results indicate the Piringer migration model, using the 'exact' calculations
      of the Migratest Lite program, predicted migrations into olive oil that were
      close to or in excess of the experimental results and gave an overestimation for
      > 95% of the migrations generated here.

PMID- 11962717
TI  - Time-temperature study of the kinetics of migration of BADGE (bisphenol-A
      diglycidyl-ether) into a fatty medium.
AB  - The migration kinetics of bisphenol-A-diglycidyl-ether (BADGE) from processed and
      non-processed model cans into vegetable oil was investigated as a function of the
      process treatment and the temperature of storage. Cans were either not heat
      treated at all or were processed at 115 degrees C for 30 min or for 1 h after
      filling with oil. Each series of experiments comprised 30 samples and was further
      divided into three groups to be stored at different temperatures (20, 40 and 60
      degrees C). Aliquots from the samples were taken at regular intervals for > 1
      year. Samples were analysed for BADGE by high-performance liquid chromatography
      with fluorescence detection. The results showed that temperature processing had
      the largest effect on migration of BADGE. Storage temperature also significantly
      influenced migration from non-processed cans, in particular at higher storage
      temperatures such as 60 degrees C. Some samples were Subjected to 60 degrees C
      storage after an initial period at 20 degrees C and an effect on migration was
      also noted, although to a much lesser extent than from processing. The results of
      migration at higher temperatures were also correlated to the potential
      degradation of BADGE from oxidation products.

PMID- 11962718
TI  - Food-contact paper and board based on recycled fibres: regulatory aspects--new
      rules and guidelines.
AB  - The question of recycled papers in contact with foods is discussed in detail with
      respect to regulatory and technical aspects. The legal context is given, and
      major existing regulations are reviewed. The safety of recycled fibre use is
      examined with respect to chemical, microbiological and organoleptic
      contamination. Toxicological testing possibilities on finished paper products are
      discussed. The harmonization work in progress at the Council of Europe level is
      presented in detail, and the authors give their personal view on future
      evolution.

PMID- 11962719
TI  - Programme on the recyclability of food-packaging materials with respect to food
      safety considerations: polyethylene terephthalate (PET), paper and board, and
      plastics covered by functional barriers.
AB  - Stimulated by new ecology-driven European and national regulations, news routes
      of recycling waste appear on the market. Since food packages represent a large
      percentage of the plastics consumption and since they have a short lifetime, an
      important approach consists in making new packages from post-consumer used
      packages. On the other hand, food-packaging regulations in Europe require that
      packaging materials must be safe. Therefore, potential mass transfer (migration)
      of harmful recycling-related substances to the food must be excluded and test
      methods to ensure the safety-in-use of recycled materials for food packaging are
      needled. As a consequence of this situation, a European research project FAIR
      CT98-4318, with the acronym 'Recyclability', was initiated. The project consists
      of three sections each focusing on a different class of recycled materials:
      polyethylene terephthalate (PET), paper and board, and plastics covered by
      functional barriers. The project consortium consists of 28 project members from
      11 EU countries. In addition, the project is during its lifetime in discussion
      with the US Food and Drug Administrations (FDA) to consider also US FDA
      regulatory viewpoints and to aim, as a consequence, to harmonizable conclusions
      and recommendations. The paper introduces the project and presents an overview of
      the project work progress.

PMID- 11962720
TI  - High dose immunosuppressive therapy and stem cell transplantation in autoimmune
      and inflammatory diseases.

PMID- 11962721
TI  - In vivo pharmacokinetics of calreticulin S-domain, an inhibitor of the classical
      complement pathway.
AB  - Inhibition of the complement system is potentially therapeutic in diseases where
      uncontrolled or overshooting complement activation plays a significant role in
      the pathogenesis of the disorder. Calreticulin (CRT) is a multifunctional protein
      whose cell-surface form (ectocalreticulin) is reported to be a C1q receptor. A
      124-residue domain within CRT, the S-domain, binds to C1q, prevents the formation
      of C1 and so inhibits activation of the classical pathway. To assess the
      usefulness of CRT S-domain as a complement inhibitor, recombinant S-domain was
      expressed, radiolabeled, and the fate of the radiolabeled peptide followed in
      vivo. In rats, CRT-S-domain shows a half-life of 1.21 +/- 0.34 and 40.5 +/- 2.7
      min in the distribution and elimination phases from plasma, respectively. The
      peptide remains largely intact, and is cleared from the circulation by the
      kidneys, where it accumulates in the proximal convoluted tubules, but is not
      excreted. Much smaller amounts of the peptide accumulate in other tissues, and
      essentially none crosses the blood-brain barrier.

PMID- 11962722
TI  - Activation of the human innate immune system by Spirulina: augmentation of
      interferon production and NK cytotoxicity by oral administration of hot water
      extract of Spirulina platensis.
AB  - Spirulina platensis is a cyanobacterial species that is surmised to potentiate
      the immune system leading to suppression of cancer development and viral
      infection. Here, we identified the molecular mechanism of the human immune
      potentiating capacity of Spirulina by analyzing blood cells of volunteers with
      pre and post oral administration of hot water extract of Spirulina. NK functions
      represented by IFN gamma production and cytolysis were enhanced after
      administration of Spirulina in >50% subjects. IFN gamma was produced in an IL
      12/IL-18-dependent fashion. In vitro stimulation of blood cells with BCG cell
      wall skeleton (CWS) allowed more potent IL-12 p40 production in cells from
      volunteers given Spirulina than in cells without pre-exposure to Spirulina. As
      BCG-CWS serves as a ligand for Toll-like receptor (TLR) 2 and 4 to raise the
      maturation stage of monocytes/macrophages, Spirulina may be involved in the
      signaling responses through Toll in blood cells even when orally administered.
      These observations indicated that in humans Spirulina acts directly on myeloid
      lineages and either directly or indirectly on NK cells. The presence of co
      operative IL-12 and IL-18 is critically important for NK-mediated IFN gamma
      production.

PMID- 11962723
TI  - HA1004, an inhibitor of serine/threonine protein kinases, restores the
      sensitivity of thymic lymphomas to Ca2+-mediated apoptosis through a protein
      kinase A-independent mechanism.
AB  - Our previous reports showed that thymic lymphomas arising in TCR transgenic mice
      are resistant to Ca2+-mediated apoptosis. Here we show that induction of
      apoptosis in thymic lymphomas involves a process that is cAMP-mediated and which
      depends on the activation of protein kinase A (PKA) despite the lower level of
      PKA type I in these lymphomas compared to thymocytes. Further, we show that
      treatment of the lymphomas with HA1004, a serine/threonine protein kinase
      inhibitor, restores their susceptibility to ionomycin-induced apoptosis. Results
      indicate that HA1004-induced restoration of sensitivity to ionomycin proceeds
      through a PKA-independent mechanism. Moreover, activation of PKA instead of its
      inhibition induces apoptosis of lymphoma cells.

PMID- 11962724
TI  - Immunomodulation as a treatment strategy for genital herpes: review of the
      evidence.
AB  - In this review, we discuss the ongoing development of a new treatment option for
      genital herpes (GH), the disease caused by herpes simplex virus (HSV) types I and
      II. Following infection, the virus establishes a latent infection in peripheral
      neurons, which periodically activates to cause recurrent skin lesions or
      asymptomatic shedding in the anogenital area. A new class of drugs, the immune
      response modifiers (IRMs), modulates the immune system against viral infection.
      This approach is currently being tested as a treatment for GH. We first review
      the effectiveness of treatment of other viral diseases with imiquimod, the first
      IRM to be licensed (Aldara, imiquimod 5% cream), and one used for the treatment
      of external anogenital warts. We then focus on resiquimod, an analog of
      imiquimod, which shows early promise as a new treatment option for GH. The
      evidence from in vitro and in vivo studies, in particular the guinea pig model of
      GH, describing the effectiveness and mode of action of this novel
      immunopharmacological agent is presented. Resiquimod stimulates specific cells of
      the innate immune system (including monocytes/macrophages, dendritic cells (DC)
      and B lymphocytes) to produce cytokines (in particular IFN-alpha, IL-12, TNF
      alpha and IFN-gamma) that initiate and drive the development of the Th1 acquired
      immune response against HSV-infected cells. Recent results from clinical trials
      and in vivo studies in animal models are consistent with the hypothesis that the
      development of HSV-specific cell-mediated immunity may prove to be the key in
      providing a long-lasting protection against GH recurrences.

PMID- 11962725
TI  - Anti-CD23 monoclonal antibody inhibits germline Cepsilon transcription in B
      cells.
AB  - A chimeric macaque/human (PRIMATIZED) anti-CD23 antibody, p6G5G1, demonstrated a
      strong inhibitory effect on IL-4 and anti-CD40 antibody-stimulated IgE production
      by human peripheral blood mononuclear cells (PBMCs). RNA analysis by both reverse
      transcription-polymerase chain reaction (RT-PCR) and Northern blot showed that
      p6G5G1 inhibited germline Cepsilon RNA synthesis, but had no effect on CD23 mRNA
      levels. These data suggest that p6G5G1 may inhibit immunoglobulin class switching
      to IgE through the inhibition of germline Cepsilon RNA synthesis. Early addition
      of p6G5G1 after stimulation by IL-4 and anti-CD40 was critical for IgE
      inhibition. In contrast, later addition of p6G5G1 still showed inhibition of
      increased levels of surface CD23, which is normally upregulated by stimulation
      with IL-4 and anti-CD40.

PMID- 11962726
TI  - Preventive administration of Mycobacterium tuberculosis 10-kDa heat shock protein
      (hsp10) suppresses adjuvant arthritis in Lewis rats.
AB  - Adjuvant arthritis (AA) can be induced in Lewis rats by immunization with
      Mycobacterium tuberculosis (Mt) in oil. We have investigated the modulation of AA
      by mycobacterial 10-kDa heat shock protein (hsp10), administered according to
      several protocols known to induce immune tolerance and immune deviation.
      Subcutaneous immunization with hsp10 in aqueous solution did not induce a
      cellular immune response, evaluated as delayed-type hypersensitivity (DTH)
      reaction, although anti-hsp10 antibodies, mainly of the IgG2a isotype, were
      detected in serum of treated animals. When rats were pretreated with hsp10 in
      aqueous solution before AA induction, no effects were seen on arthritis-induced
      joint swelling, although osteolysis and lymphocyte infiltration were slightly
      decreased. When other routes of administration were attempted, the strongest
      suppression was seen in the group of animals which received four intranasal
      (i.n.) administrations of protein and a subsequent challenge of hsp10 in
      incomplete Freund's adjuvant (IFA). We also found that the extent of disease
      suppression among the different groups of animals correlated with serum anti
      hsp10 antibody levels. These antibodies mostly belonged to the IgG2a subtype,
      suggesting that immune deviation may play a role in the mechanism of disease
      suppression by hsp10.

PMID- 11962727
TI  - Lactoferrin immunomodulation of DTH response in mice.
AB  - Improved nontoxic adjuvants, especially adjuvants capable of inducing cell
      mediated immunity (CMI), are needed for research in immunology and for
      development of human and veterinary vaccines. Bovine Lactoferrin, an effector
      molecule shown to directly participate in host defense, was assessed at various
      concentrations as an adjuvant component for induction of DTH responses to sheep
      red blood cells (SRBC). Subcutaneous immunization with Lactoferrin enhanced
      delayed type hypersensitivity (DTH) in CBA mice in a dose-dependent fashion; DTH
      responses were most significantly increased when sensitization was accomplished
      using Lactoferrin at 50 microg/dose and 250 microg/dose. Furthermore, Lactoferrin
      admixed with suboptimal dose of SRBC enhanced DTH responses by over 17-fold.
      Peritoneal cells collected from mice intraperitoneally injected with a 100
      microg/dose of Lactoferrin demonstrated modest, but significant, production of
      TNF-alpha, IL-12 and MIP-1alpha when cultured in vitro, compared to saline
      injected controls. J774A.1 murine macrophages stimulated with Lactoferrin
      resulted in increased TNF-alpha protein production, and upregulated IL-12 and IL
      15 mRNA. Levels of message for chemokines MIP-1alpha and MIP-2 were also
      increased in a dose-dependent way. Taken together, these results indicate that
      Lactoferrin as an adjuvant may stimulate macrophages to generate a local
      environment likely to push immune responses towards development and maintenance
      of CMI.

PMID- 11962728
TI  - Effects of chronic mild stress on lymphocyte proliferative response.
      Participation of serum thyroid hormones and corticosterone.
AB  - There is increasing evidence that stress produces changes in various immune
      processes. Some of these changes may be due to neurochemical and hormonal
      alterations including thyroid hormones levels. This work was carried out to study
      the impact of chronic mild stress (CMS) exposure on proliferative responses and
      its correlation with serum thyroid hormone levels. In addition, the influence of
      serum corticosterone levels on these responses was also studied. For this
      purpose, mice were submitted from1 to 6 weeks to a CMS model. After undergoing
      the stress schedule for 4 weeks, an alteration in the proliferative response was
      observed. Lymphocytes from exposed animals showed a decrease in T-cell response
      to concanavalin-A (Con A) and phytohemagglutinin (PHA) and an increase in B-cell
      proliferation to lipopolysaccharides (LPS). In parallel, a reduction in T3 and T4
      serum levels was observed. On the contrary, serum corticosterone levels increased
      in animals exposed to CMS for 1 or 2 weeks and then return to normal values.
      Lowering serum thyroid hormone levels by propylthiouracil (PTU) treatment
      negatively modulates T-cell response without affecting B-cell response. On the
      other hand, the substitutive T4 treatment in stressed animals improved
      significantly the proliferative T-cell response. Non-significative changes in
      CD4/CD8 ratio were observed neither in stressed, PTU- or T4-treated animals.
      Taken together, our results suggest an impact of chronic stress on thyroid
      function that in turn alters T-cell response. These findings may help to
      elucidate the physiological mechanisms through which stress plays a roll in the
      etiology of many diseases.

PMID- 11962730
TI  - Fosfomycin inhibits neutrophil function via a protein kinase C-dependent
      signaling pathway.
AB  - We investigated effects of fosfomycin (FOM) on neutrophil function, specifically
      the oxidative burst and adhesion molecule expression (CD11b/CD18, or MAC-1) using
      flow cytometry assay. Preincubation of polymorphonuclear leukocytes (PMNL) with
      FOM from 1 to 100 microg/ml prior to stimulation by phorbol 12-myristate 13
      acetate (PMA, 2 ng/ml) significantly suppressed the oxidative burst in a
      concentration-dependent manner. However, FOM did not affect the oxidative burst
      of PMNL stimulated by a chemotactic peptide, N-formyl-methionyl-leucyl
      phenylalanine (FMLP). Stimulation with PMA (2 ng/ml) caused a rapid up-regulation
      of CD11b surface expression on PMNL, followed by time-dependent loss of this
      receptor. FOM also suppressed loss of CD11b in PMNL stimulated by PMA. FOM then
      inhibits the PMA-induced oxidative burst and CD11b epitope loss in PMNL. The
      suppressive effect appears to be mediated by the protein kinase C-dependent
      signaling pathway.

PMID- 11962729
TI  - Roles of bradykinin in vascular permeability and angiogenesis in solid tumor.
AB  - Bradykinin (BK) is involved in tumor angiogenesis. To elucidate the mechanism
      underlying BK-induced angiogenesis, we evaluated the roles of BK in tumor
      associated vascular permeability and angiogenesis in the different phases of
      tumor development in mice bearing sarcoma 180 cells. The vascular permeability
      was significantly enhanced in the early growth phase (which peaked at day 5), and
      was thereafter markedly reduced. By contrast, tumor angiogenesis increased
      gradually over a 20-day experimental period. Oral administration of a B2 receptor
      antagonist, FR173657 (30 mg/kg/day), significantly suppressed the vascular
      permeability, but a B1 antagonist, desArg10-Hoe140 (1 mg/kg/day) did not. An
      immunohistochemical study revealed the presence of immunoreactive B2 receptor in
      the endothelial cells in the early phase, whereas B2 receptors were also observed
      in the stromal fibroblasts in the late phase. We also found that VEGF was
      detected exclusively in the stromal fibroblasts only in the late phase.
      Furthermore, VEGF immunoreactivity was attenuated by the treatment with FR173657.
      Tumor angiogenesis was significantly reduced by treating the tumor tissues with
      FR173657 both in the early phase (days 1-6, 30 mg/kg/day, oral administration)
      and in the late phase (days 7-12, 30 mg/kg/day, oral administration), whereas it
      was inhibited by neutralization with anti-VEGF antibody (1 microg/site/day, local
      injection) only in the late phase. These results suggest that BK would promote
      angiogenesis by increasing vascular permeability in the early phase via B2
      receptor in the endothelial cells and by promoting up-regulation of VEGF via B2
      receptor in the stromal fibroblasts in the late phase.

PMID- 11962731
TI  - Malondialdehyde-acetaldehyde-haptenated protein induces cell death by induction
      of necrosis and apoptosis in immune cells.
AB  - Recent studies have demonstrated that circulating antibodies against
      malondialdehyde-acetaldehyde (MAA)-haptenated proteins are significantly
      increased in patients with alcohol-induced cirrhosis and hepatitis and correlate
      with the severity of liver damage. Additionally, when proteins are haptenated
      with MAA, they become highly immunogenic in vivo in the absence of adjuvants.
      However, the mechanism(s) of this immunogenicity are currently unknown. Initial
      in vitro studies on the effects of MAA-modified proteins on cells demonstrated an
      increase in cell death at concentrations that were cell type specific and time
      dependent. Since immunogenicity due to cell death has been described, we
      investigated the mechanism(s) by which cell death was occurring. Assessment of
      cell death in splenocytes after 1 h found significant levels of apoptosis as
      compared to controls. After 5 h, a significant and dose-dependent necrosis
      occurred in which cells were exposed to >62.5 microg/ml (43.1 mM) MAA-haptenated
      protein. After 24 h, exposure to >31.3 microg/ml (21.6 mM) MAA-haptenated protein
      resulted in significant levels of necrosis, although DNA laddering studies found
      apoptosis was occurring as well. Morphological changes in the cells were observed
      by light microscopy that correlated with a "low" forward scatter population by
      flow cytometry. Since necrosis has been implicated in enhancing both primary and
      secondary immune responses, and necrosis was predominantly occurring in response
      to MAA-haptenated proteins, a possible mechanism by which the immunogenicity of
      MAA modification of proteins in vivo may occur is suggested. Specifically, MAA
      modification of self proteins may result in the death of various cell types, most
      likely those in the liver. These necrotic materials may induce anti-MAA
      antibodies and other auto antibodies, whose levels may then correlate with the
      severity of ALD.

PMID- 11962732
TI  - Effect of the cannabinoid receptor ligand, WIN 55,212-2, on superoxide anion and
      TNF-alpha production by human mononuclear cells.
AB  - Cannabinoids are known to downregulate immune response but the role for
      cannabinoid receptors in cannabinoid-induced immunosuppression is still unclear.
      To address this question, the interference of CB1 and CB2 receptor antagonists
      with the inhibition of TNF-alpha production by synthetic cannabinoid WIN 55,212-2
      was studied using human peripheral blood mononuclear cells (PBMC) in vitro. CB2
      (SR 144528) but not CB1 (SR 141716A) receptor antagonist dose dependently
      interfered with WIN 55,212-2-induced inhibition of TNF-alpha synthesis. Also, WIN
      55,212-2 decreased fMLP-induced reactive oxygen species generation in
      lipopolysaccharide (LPS)-primed PBMC. However, the high concentrations of
      cannabinoid receptor ligands needed to achieve significant effects suggest that
      the observed effects may be in part cannabinoid receptor independent.

PMID- 11962733
TI  - Chalcones from Chinese liquorice inhibit proliferation of T cells and production
      of cytokines.
AB  - Licochalcone A (LicA), an oxygenated chalcone, has been shown to inhibit the
      growth of both parasites and bacteria. In this study, we investigated the effect
      of LicA and four synthetic analogues on the activity of human peripheral blood
      mononuclear cell proliferation and cytokine production. Four out of five
      chalcones tested inhibited the proliferation of lymphocytes measured by thymidine
      incorporation and by flow cytometry. The production of pro- and anti-inflammatory
      cytokines from monocytes and T cells was also inhibited by four of five
      chalcones. Furthermore, intracellular detection of cytokines revealed that the
      chalcones inhibited the production rather than the release of the cytokines.
      Taken together, these results indicate that LicA and some analogues may have
      immunomodulatory effects, and may thus be candidates not only as anti-microbial
      agents, but also for the treatment of other types of diseases.

PMID- 11962734
TI  - BmTI antigens induce a bovine protective immune response against Boophilus
      microplus tick.
AB  - Boophilus microplus trypsin inhibitors (BmTIs) present in larvae were
      preliminarily characterized as active proteins, approximately 10-18 kDa, by SDS
      PAGE. BmTIs showed trypsin inhibitory activity on reverse zymography containing
      gelatin (0.03%) and also inhibited others serine proteinases (human neutrophil
      elastase and human plasma kallikrein). Bos indicus, Nelore breed calves,
      previously sensitized with BmTIs and challenged with tick larvae (20,000
      larvae/animal), showed 72.8% efficacy to interfere in tick development with 69.7%
      and 71.3% reduction of both tick number and egg weight, respectively. Cattle
      BmTls antiserum titer was approximately 1:8000. The maximum level of BmTls
      antibody production was detected 40 days after the first immunization by ELISA.
      Our preliminary results suggest that B. microplus serine proteinase inhibitors
      may play a role in the tick larvae fixation and feeding processes. Therefore, the
      development of antibodies against BmTIs might impair the normal parasitism.

PMID- 11962735
TI  - The natural plant product tryptanthrin ameliorates dextran sodium sulfate-induced
      colitis in mice.
AB  - The therapeutic effects of tryptanthrin (TRYP), a natural product from the
      medicinal plant Polygonum tinctorium, were examined in a murine model of
      inflammatory bowel disease (IBD). Colitis was induced by 5% dextran sodium
      sulfate (DSS) in drinking water for 7 days from day 0. TRYP (100 mg/kg) was
      administered orally suspended in 5% arabia gum everyday from day 3 for 5 days.
      Histopathological analysis showed reduced colon damage in TRYP-treated mice on
      day 6; however, colon injury resumed after treatment was stopped. The production
      of prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and nitric
      oxide (NO) by untreated and treated mouse colon tissues cultured in vitro were
      mostly unchanged by TRYP treatment. However, mitogen-stimulated spleen cells from
      TRYP-treated colitic mice produced less interleukin 2 (IL-2) and less interferon
      gamma (IFN-gamma) than untreated colitic mouse spleen cells, early after
      induction of colitis. When colitis was induced with 5% DSS for 7 days and TRYP
      was given to the mice for 8 days from day 3, TRYP enhanced the survival of the
      mice but results were not significant. A significant reduction of weight loss was
      observed in TRYP-treated mice with colitis induced by 5% DSS for 4 days as
      compared to control mice. Remarkably, whereas 90% of the vehicle-treated mice
      died from wasting disease, all the TRYP-treated mice survived, suggesting that
      TRYP may have a therapeutic effect on colitis.

PMID- 11962736
TI  - Toll-like receptor 2 is at least partly involved in the antitumor activity of
      glycoprotein from Chlorella vulgaris.
AB  - Toll-like receptors (TLR) are involved in innate immunity by recognizing various
      bacterial components. We have previously reported that an active substance of ARS
      2 purified from the culture medium of Chlorella vulgaris was a glycoprotein with
      a molecular weight of 63,100 amu and that this glycoprotein expressed antitumor
      activity, with the protein moiety in ARS-2 being necessary for this antitumor
      activity. Here, we show that ARS-2 stimulated spleen-adherent cells from C3H/HeJ
      lacking functional TLR4 to produce interleukin-12 (IL-12) p40, whereas such
      cytokine production was significantly impaired in ARS-2-stimulated spleen
      adherent cells from TLR2 knockout mice. The overexpression of mouse TLR2 (mTLR2)
      and mouse CD14 (mCD14) conferred the ARS-2 inducibility of nuclear factor-kappaB
      activation to human HEK 293 cells. These results suggest that TLR2 signaling is
      at least partly involved in the antitumor activity of the water-soluble antitumor
      glycoprotein from C. vulgaris.

PMID- 11962737
TI  - Effect of liposomal antigens on the priming and activation of the immune system
      by dendritic cells.
AB  - Dendritic cells (DCs) are recognized as the sole professional antigen-presenting
      cells capable of priming naive T cells of the helper and cytotoxic phenotypes.
      This property is presently exploited with success in vaccinal strategies against
      pathogens or tumor cells that otherwise escape immune recognition, but the
      repeated infusions of ex vivo expanded and sensitized DCs are usually required to
      achieve protection. In this paper, we demonstrate that liposomal antigens can
      efficiently relay and propagate the action of DCs, inducing a strong long-term
      response against their associated antigen. Their effect is mainly achieved by
      improving the ex vivo loading of DCs and by efficiently channeling the activation
      stimulus into the induction of effector function. This is demonstrated by the
      sustained immunoglobulin production as well as by the sustained
      lymphoproliferation and the increased cytokine secretion that can be achieved
      upon restimulation of DC-primed immune cells with limited amount of liposomal
      antigenic material. Being well-tolerated and easily prepared, liposomal antigens
      could therefore be expected to significantly contribute to the efficiency and to
      a more general utilization of the highly promising but rather cumbersome DC-based
      immunotherapies.

PMID- 11962739
TI  - Immunogold localization of mitochondrial aspartate aminotransferase in
      mitochondria and on the cell surface in normal rat tissues.
AB  - Mitochondrial aspartate aminotransferase (mAspAT) (E.C. 2.6.1.1), an important
      enzyme in amino acid metabolism, is identical to a fatty acid-binding protein
      (FABPpm) isolated from plasma membranes of several cell types. Employing a
      monospecific polyclonal antibody to rat mAspAT, we have used immunogold electron
      microscopy to study the subcellular distribution of mAspAT in various mammalian
      tissues. Immunogold labeling of rat tissue sections embedded in LR Gold resin
      showed strong labeling of mitochondria in all tissues examined (viz. liver,
      pancreas, pituitary, spleen, heart, kidney, submandibular gland). In addition,
      strong and specific labeling was also observed at a number of non-mitochondrial
      sites including various locations in kidney, such as on cell surface in distal
      tubules and cortical collecting ducts, in condensing vacuoles, along cell
      boundaries between adjoining cells, and in endothelial cells lining capillaries
      in the glomerulus. Surface labeling due to mAspAT was also seen in arteriolar
      endothelial cells and in lymphocytes. These findings support the previous
      identification of mAspAT as both a mitochondrial enzyme and a plasma membrane
      protein. It is suggested that in accordance with its established role in other
      cells and tissues, the surface-located mAspAT in kidney and endothelial cells is
      involved in the fatty acid transport process. The dual-localization of mAspAT, as
      well as a large number of other mitochondrial proteins (viz. Hsp60, Hsp10,
      Cytochrome c, TRAP-1 and P32 (gC1q-R)) in recent studies, within both
      mitochondria and at various specific extramitochondrial sites raises fundamental
      questions about the role of mitochondria in cell structure and function, and
      about the mechanisms that exist in normal cells for protein translocation from
      mitochondria to other compartments. These results have implications for the role
      of mitochondria in apoptosis and different diseases.

PMID- 11962738
TI  - Immunohistochemical analysis of beta3 integrin (CD61): expression in pig tissues
      and human tumors.
AB  - CD61 is a membrane glycoprotein that associates with CD41 (alphaIIb) to form the
      heterodimeric complex gpIIb/IIIa (CD41/CD61), predominantly expressed in
      platelets and megakariocytes. CD61 or beta3 integrin also associates with alpha v
      (CD51) to form the vitronectin receptor, which is expressed in many tissues. We
      have used a monoclonal antibody against the porcine gpIIIa or CD61 (JM2E5) to
      study the distribution of this molecule in different normal pig tissues. As in
      humans, CD61 was broadly expressed in all tissues examined. In the kidney, strong
      expression of CD61 was observed in epithelial cells from renal tubules. In the
      testis, CD61 expression was detected in the Leydig cells. However, in liver, CD61
      was weak or not detected. Many integrins are particularly involved in
      tumogenicity and in tumor progression mediating cell-cell interaction.
      Immunofluorescence experiments using cultured human tumor HeLa cells showed
      nuclear and cytoplasmic staining of mAb JM2E5. Immunohistochemical analysis of
      human tumor sections from several organs showed a heterogeneus distribution in
      metastatic cases from colon and breast carcinoma. However, no staining was found
      in metastasis from melanoma.

PMID- 11962740
TI  - Time-dependent effects of maternal continuous propranolol on fetal lung
      development in rats.
AB  - Previous studies have demonstrated a role for the beta-adrenergic system in the
      maturation of the fetal alveolar epithelium. Chronic blockade of beta-adrenergic
      binding sites has been shown to adversely effect physiologic and biochemical
      indices of fetal lung maturation. In the present study timed-pregnant female
      Sprague-Dawley rats were treated with a continuous 0.5 mg/hr dose of propranolol
      HCl, or saline, via an osmotic pump. The treatment periods were days 18-21, or 20
      23 of gestation. Fetal body weights were obtained, and the morphology of the
      fetal lungs studied by light and electron microscopy. Cytoplasmic volume
      densities of lamellar inclusion bodies and glycogen within developing type II
      alveolar epithelial cells were also determined. In addition, total phospholipids
      (as phosphorus) and glycogen content were determined biochemically. The fetuses
      from females treated from day 20-23 demonstrated no differences between saline
      treated and propranolol-treated groups, in either fetal weight or the morphologic
      appearance of the developing lung. In contrast, the fetuses from mothers treated
      from day 18-21 with propranolol were significantly smaller, and their lungs
      appeared less mature than saline-treated counterparts. The glycogen content of
      developing type II alveolar epithelial cells was significantly more abundant (as
      judged by stereologic and biochemical analyses) in the propranolol-treated
      fetuses. In addition, total phospholipids were decreased in the propranolol
      treated 21-day fetuses. The results of the present study suggest that the
      development of the alveolar epithelium is sensitive to continuous beta-adrenergic
      blockade by propranolol during a critical time late in gestation.

PMID- 11962741
TI  - Effects of cigarette smoke exposure on the ultrastructure of the golden hamster
      parathyroid gland.
AB  - Cigarette smoking has been identified as one of the risk factors to induce
      osteoporosis. However, we find no study on the morphology of the parathyroid
      gland under smoking exposure. We studied the ultrastructure of the parathyroid
      gland, lung and femur of the golden hamster exposed to cigarette smoke. Four-week
      old male hamsters were housed in a plastic case (48x31x30 cm) and were exposed to
      cigarette smoke for 12 weeks, 5 minutes exposure, 4 times a day, 4 days a week.
      There were no differences in serum calcium level and the whole bone mineral
      density between the control and the smoke-exposed groups. In the parathyroid
      gland of the smoke-exposed animals, the Golgi complexes associated with many
      prosecretory granules were well developed and many secretory granules were
      located near the plasma membrane. Large lipid-like inclusion bodies were observed
      in the alveolar macrophages of the smoke-exposed animals. The femur morphology
      showed a wider area of resorbing surface in the smoke-exposed group than in the
      control group. From these findings, it is conceivable that the secretory activity
      of the parathyroid gland was stimulated with cigarette smoke exposure.

PMID- 11962742
TI  - Pressure volume curve and alveolar recruitment/de-recruitment. A morphometric
      model of the respiratory cycle.
AB  - HYPOTHESIS: The changes in pulmonary volume taking place during respiration are
      accompanied by the opening and closing of the alveoli, with the number of alveoli
      open, at the same transpulmonary pressure (TPP) differing, depending on whether
      the lung is insufflated or deflated. MATERIAL AND METHODS: Seventy 344 Fischer
      rats divided into five groups. Group 1 lungs were fixed by instilling 10%
      formalin through the trachea to a pressure of 25 cm H2O. The lungs of the next
      four groups were air-filled and fixed via the pulmonary artery: group 2 lungs
      were fixed in inflation at 10 cm H2O TPP; group 3 lungs were fixed in inflation
      at 20 cm. H2O TPP; the lungs of groups 4 and 5 were fixed in deflation and,
      therefore, were inflated with air up to 27 cm. H2O to drop to 20 cm in group 4
      and to 10 cm in group 5. The lungs were processed for light microscopy, carrying
      out a morphometric study. The results were statistically processed. RESULTS: The
      lungs insufflated with liquid fixative at 25 cm of TPP reached higher values in
      the variables Pulmonary Volume, Internal Alveolar Surface (IAS) and Number of
      Alveoli, being statistically significant (p < 0.05) in comparison with the other
      four groups. In the lungs fixed in deflation, the pulmonary volume, IAS and
      number of alveoli were greater than in those fixed in inflation. The lungs fixed
      to 20 cm in deflation displayed significant statistical differences compared with
      those fixed to 20 cm in inflation. The IAS and number of alveoli gave good rates
      in relation with the pulmonary volume (r > or = 0.65). Three variables were used
      to measure the size of the alveoli, alveolar cord, alveolar surface and Lm, but
      none showed significant modifications. CONCLUSION: This study supports the
      hypothesis that changes in lung volume are related to the increase/decrease in
      the number of alveoli that are open/closed and not to the modification in the
      size of the alveoli. Alveolar recruitment is the microscopic expression of
      pulmonary hysteresis, since the number of alveoli open in deflation is greater
      than the number open during inflation.

PMID- 11962743
TI  - Abnormalities in dendritic cell and macrophage accumulation in the pancreas of
      nonobese diabetic (NOD) mice during the early neonatal period.
AB  - Dendritic cell (DC), macrophage (Mphi) and lymphocyte infiltrations have been
      observed in normal human perinatal pancreata, but have never been investigated so
      early in control mice. In type 1 diabetes-prone NOD mice, these cells are thought
      to infiltrate first the periphery of the islets of Langerhans around weaning
      before further islet infiltration and beta-cell destruction. We quantified,
      during the first month of life, the numbers of DC (characterized by CD11c
      positivity and dendritic morphology), histiocyte-like Mphi (characterized by ER
      MP23 positivity) and Mphi with scavenging potential (characterized by BM8
      positivity) in C57BL/6, DBA/2 and BALB/c control, and NOD and lymphocyte
      deficient NODscid mouse pancreata. First, CD11c+ DC were present at low densities
      from birth onwards in control pancreata, while densities were higher in NOD and
      NODscid. Second, high numbers of BM8+ and ER-MP23+ Mphi were observed at birth in
      all strains investigated. After birth, particularly BM8+ cells disappeared
      progressively in control strains, but not in NOD and NODscid. Third, NOD mice
      also had more ER-MP23+ Mphi at birth compared to controls. Finally, DC and Mphi
      localizations were similar in all strains, i.e., mostly as dispersed cells in
      perivascular, periductular, peri-islet areas and interlobular septa. The most
      remarkable finding was that particularly BM8+ Mphi, were seen at sites of islet
      neogenesis and predominantly at the duct-islet interface. Our data showed that
      different types of APC were present in the pancreas during postnatal development
      in various control mouse strains and some differences were observed in NOD and
      NODscid mice from birth onwards.

PMID- 11962744
TI  - Ploidy and chromatin pattern analysis as an aid for cervical smear diagnosis.
AB  - In the present study we used computer-assisted microscopy to analyze the
      morphology of Feulgen-stained cell nuclei in cell populations obtained at the
      same time as routinely performed cervical smears and in the same way. We
      investigated in a series of 110 cases whether the quantitative morphonuclear
      description of cytological cervical samples is able to aid pathologists to
      distinguish between benign and more suspect premalignant lesions. For this task
      nuclear DNA content, nuclear morphometry (size and anisonucleosis level) and
      chromatin pattern-related parameters were compiled for each specimen enrolled in
      the database. A set of 32 normal and 17 high-grade squamous intraepithelial
      lesion (HSIL) specimens (with diagnostic confirmations) were selected as
      references and used to establish a discriminant model on the basis of cytometry
      generated variables. This model was then used to score the remaining 61 cases in
      our series (including cases exhibiting benign cellular changes, squamous cells of
      undetermined significance, low-grade SIL and cancers). The results show that a
      model discriminating efficiently between normal and HSIL groups can be obtained
      by combining 5 quantitative features (1 DNA ploidy-related, 2 morphometrical and
      2 chromatin texture features). A 97% specificity and an 88% sensitivity
      characterized the boundary so established. When applied to new cases, the model
      was in fact able to correct diagnoses for cases which had been down- or up-graded
      on the basis of the Bethesda system, and provided scores in accordance with
      histological control.

PMID- 11962745
TI  - In situ demonstration of both TUNEL-labeled germ cell and Sertoli cell in the
      cimetidine-treated rats.
AB  - Cimetidine has caused dysfunction in the male reproductive system. In the rat
      testis, intratubular alterations and loss of peritubular tissue due to
      peritubular myoid cell death by apoptosis have been recently shown. Thus, the aim
      of this study is to evaluate which cells of the seminiferous epithelium have been
      affected and/or died by apoptosis after the treatment with cimetidine. For this
      purpose, an experimental group containing five male albino Wistar rats received
      intraperitoneal injections of cimetidine (50 mg/kg body weight) during 52 days.
      The testes were fixed with 4% buffered formaldehyde and were embedded in
      paraffin. For detection of DNA breaks (apoptosis) in the cells of the
      seminiferous epithelium, the testicular sections were treated by the TUNEL method
      (Apop-Tag Plus Peroxidase Kit). In the tubules affected by cimetidine, altered
      peritubular tissue, including the presence of TUNEL labeling in the myoid
      peritubular cells, were usually found. In these tubules, the seminiferous
      epithelium exhibited low density of germ cells and TUNEL-positive labeling in the
      germ cells of the basal compartment. The concomitant staining in both germ cells
      of the basal compartment and late spermatids suggest a sensitivity of these cells
      in the damaged tubules. Besides germ cells, TUNEL-positive Sertoli cells were
      also found in the injured seminiferous tubules. Thus, a relationship between
      dying germ cells and Sertoli cell damage and/or death must be considered in
      tubules where peritubular tissue has been affected by toxicants.

PMID- 11962746
TI  - Age-related changes in the dorsal skin histology in Mini and Wistar rats.
AB  - Mini rats (Jcl: WistarTGN(ARGHGEN)1Nts (MRs) are Wistar rat (WR)-derived
      transgenic rats in which the expression of growth hormone (GH) gene is suppressed
      by the presence of antisense transgene. The plasma GH level of MRs is reduced to
      40 to 60% of that of WRs. In this study, to evaluate the influence of GH
      deficiency on the skin nature, age-related changes in the dorsal skin histology
      were compared between male MRs and WRs. Although there were no essential
      differences in the skin structures between the two strains, MRs had thinner skin
      with less collagens, more abundant subcutaneous adipose tissues and small-sized
      sebaceous glands compared with WRs. On the other hand, the hair cycle evaluated
      by the morphology and the depth of hair follicles was greatly different between
      them. Namely, two cycles of 4 weeks each were observed in both strains during the
      first 8 weeks after birth, but the cycle entered a long-lasting quiescence
      (telogen phase) in MRs while the 3rd cycle started in WRs afterwards. The lower
      level of serum insulin-like growth factor (IGF)-1 in MRs may be related to such a
      difference in hair cycle pattern, although the levels of IGF-1 and IGF-1 receptor
      mRNAs in the dorsal skin tissues were similar between MRs and WRs. MRs are
      considered to be a useful animal model for dermatopathy in patients suffering
      from GH deficiency and for grasping a clue to elucidate the exact effects of GH
      on the skin nature, especially on hair follicle development.

PMID- 11962747
TI  - Disorganization of honey-comb immunoreactive pattern of desmin and plectin in rat
      atrophic soleus muscle fiber induced by hindlimb suspension.
AB  - Immunoreactivity for desmin, plectin and alpha-actinin was investigated in rat
      atrophic soleus muscle fibers induced by hindlimb suspension between 1 and 4
      weeks (hindlimb suspension group, HSG), and compared with that of the control
      group (CG). Some of the HSG for 4 weeks were allowed unrestricted cage activity
      for 2 weeks as the recovery group (RG). In the cross-sectioned muscle fibers of
      the CG, desmin and plectin showed honey-comb immunoreactive patterns extending
      throughout the sarcoplasm. Superimposed images by double immunofluorescence
      labeling showed overlapping of both immunoreactivities. In the longitudinally
      sectioned profiles, superimposed images of alpha-actinin and desmin were
      overlapped at the level of Z-discs. The focal disorganization of the above
      honeycomb immunoreactive patterns, followed by the reduction of the cross
      sectional area (CSA) of atrophic soleus muscle fibers and the appearance of Z
      streaming, uniquely arose in the HSG from the first week and extended throughout
      the sarcoplasm in proportion to the suspension period. Such honey-comb patterns
      of both desmin and plectin were already restored in the RG at 2 weeks, followed
      by the disappearance of Z-streaming, prior to the recovery of the CSA. These
      findings indicate that the disorganization of topological and structural
      relationships of desmin and plectin with Z-discs surrounding individual
      myofibrils is primarily evoked, which leads to Z-streaming of atrophic soleus
      muscle fibers, and that the restoration of the muscle activity results in an
      early arrangement recovery of desmin and plectin around myofibrils.

PMID- 11962748
TI  - Recovery process of arthritis induced by 6-sulfanilamidoindazole (6SAI) in rats.
AB  - 6-Sulfanilamidoindazole (6SAI) is known to induce not only an acute arthritis but
      also serositis and arteritis which resemble those induced by some vasodilators in
      rats. In this study, the recovery process of ankle lesions was examined
      histopathologically for up to 12 weeks of recovery period in rats bearing
      arthritis induced by administration of 6SAI (500 mg/kg) for 2 weeks. At 2 weeks
      of 6SAI-treatment, exudative synovitis and exudative/edematous periarthritis with
      marked formation of granulation tissues and periosteal reactive bone formation
      were noted in the ankles, but no remarkable neutrophil infiltration was detected
      in those lesions. The ankle swelling induced by 6SAI diminished by 4 weeks of
      recovery period, and the elevated plasma fibrinogen levels were normalized by 2
      weeks of recovery period. Although fibrosis and newly-formed periosteal bone were
      still observed after 2 weeks of recovery period, no inflammatory lesion was
      detected at that point. At 4 or 12 weeks of recovery periods, the ankles showed
      an almost normal appearance. These results indicate that 6SAI-induced arthritis
      is reversible in nature and does not develop into chronic phase.

PMID- 11962750
TI  - Three-dimensional architecture of the connective tissue core and surface
      structures of the lingual papillae in the rabbit.
AB  - Three-dimensional characteristics of the epithelial cell layer and connective
      tissue interface of the tongue were studied using scanning electron microscopy.
      In this study, the fragments of tongue were fixed in modified Karnovsky's
      fixative solution. Subsequently, the specimens were treated with 10% NaOH
      solution for 4-7 days at room temperature and postfixed in 1% OsO4 in 0.1 M
      phosphate buffer (pH 7.4) for 2 hours at 4 degrees C. They were dehydrated
      through a graded ethanol series, and critical-point dried with CO2. The specimens
      were coated with gold and observed in a scanning electron microscope, JEOL JSM
      6100. The results showed numerous papillae on the dorsal surface of the tongue
      divided into four groups (filiform, fungiform, foliate and vallate papillae).
      Filiform papillae are conically shaped; fungiform papillae have an irregular
      round surface; foliate papillae are oval in shape and have some parallel
      projections; and vallate papillae are located in the posterior part of the tongue
      and have a depression around the center. After the treatment with 10% NaOH
      solution, the original arrangements of connective papillae could be seen. This
      characteristic three-dimensional distribution of the collagen fiber bundles is
      typical for each superficial papillae depending on whether it is filiform,
      fungiform, foliate or vallate.

PMID- 11962749
TI  - Changing pattern of cytokeratin 7 and 20 expression from normal epithelium to
      intestinal metaplasia of the gastric mucosa and gastroesophageal junction.
AB  - It is currently unclear whether intestinal metaplasia at the esophagogastric
      junction and in the distal esophagus represent a continuum of the same underlying
      disease process, i.e., gastroesophageal reflux, or constitute different entities
      with a different pathogenesis. Biopsies below the Z line might show specialized
      epithelium in some patients and the question is whether this is another form of
      short segment Barrett's esophagus or whether it is related to a generalized
      atrophic process of the stomach. Data from recent studies regarding the
      expression of cytokeratin CK7 and CK20 in intestinal metaplasia (IM) found at the
      gastroesophageal junction are conflicting. Prompted by these data we undertook
      the present study: a) to evaluate the expression of CK7 and CK20 in IM of the
      gastric cardia and to compare the findings with those in patients with Barrett's
      esophagus and IM of the gastric corpus and antrum mucosa; and b) to evaluate the
      immunophenotype of non-intestinalized cardiac mucosa and to compare it with that
      of normal gastric epithelium. We studied the expression of CK7 and CK20 on biopsy
      specimens from patients with long-segment Barrett's esophagus (n=17) and surgical
      resection and biopsy specimens of gastric cardia (n=15), corpus (n=14) and antrum
      (n=22) from patients with histological evidence of IM. Eighty-four biopsy
      specimens from 42 patients (antrum n=15, corpus n=20, cardia n=7) without
      evidence of IM were studied as a control group. We observed an immunophenotype
      characterised by diffuse moderate to strong CK7 staining on the surface and crypt
      epithelium combined with strong CK20 staining on the surface and superficial part
      of the crypts in 94.1% (16/17) of the cases with long-segment Barrett's
      esophagus, but in none of the 36 cases with IM in distal stomach (antrum and
      corpus). IM in the gastric cardia expressed the immunophenotype seen in IM of the
      gastric mucosa in 93.3% (14/15) of the cases. On the other hand, normal cardiac
      epithelium expressed patchy strong CK7 staining on the surface epithelium and on
      both, superficial and deep parts of the pits combined with patchy strong CK20
      staining on the surface epithelium and superficial pits, a feature permitting
      distinction of the normal cardiac epithelium from those of the normal gastric
      antrum and corpus epithelium. We conclude that the expression of cytokeratins 7
      and 20 can be used to distinguish the origin of IM of the gastroesophageal
      junction. The CK7/20 immunophenotype of IM in the gastric cardia closely
      resembles that of the IM in the gastric antrum and corpus and is different from
      IM in long-segment Barrett's esophagus. In contrast, the CK7/20 immunophenotype
      of the cardiac epithelium is different from that of the gastric antrum and corpus
      mucosa, suggesting that cardiac epithelium might not be a native normal gastric
      epithelium but one that is acquired as a consequence of longstanding
      inflammation. Changing pattern of CK7 and CK20 expression from normal to
      intestinalized epithelium suggests that IM arising from cardiac epithelium might
      have distinctive features.

PMID- 11962751
TI  - Effect of heparin and antivenom on skeletal muscle damage produced by Bothrops
      jararacussu venom.
AB  - We examined the effect of treatment with heparin and polyvalent antivenom on mice
      muscle Extensor digitorum longus (EDL) regeneration, after damage induced by
      injection of Bothrops jararacussu crude venom over the muscle of the right
      posterior limb. The mice were separated into groups and each group received
      treatment, by intravenous route with either high molecular weight heparin (H),
      low molecular weight heparin (LMWH), polyvalent antivenom (PAV) or with the
      combination of PAV plus H or PAV plus LMWH at 15 minutes and 4 hours after the
      injection of the venom. Myotoxicity was measured by the increase in plasma
      creatine kinase (CK) activity at two hours after the injection of the venom. The
      histological changes in EDL at 1, 3, 7 and 21 days after the injection of the
      venom were analyzed by light microscopy. In each group the normal and regenerated
      muscle fibers were quantified using Scion Image computer program. We also
      evaluated in vitro, the influence of these substances in the proteolytic and
      phospholipase activities of the venom. Heparins decreased the proteolytic
      activity of the venom but did not affect its phospholipase activity. However the
      PAV antagonized both activities. PAV and its combinations showed antimyotoxic
      activity, according to the magnitude of CK plasma levels. At 21 days the
      regeneration was observed in all animals, also in those that received only the
      venom. All treatments, except LMWH, promote a significant increase in the number
      of muscle fibers.

PMID- 11962752
TI  - Tetranectin expression in gastric adenocarcinomas.
AB  - AIMS: The aim was to analyze the immunohistochemical localization of tetranectin
      in gastric adenocarcinomas and the adjacent tissues of the wall of the stomach.
      METHODS AND RESULTS: Forty cases of gastric adenocarcinomas were stained by the
      indirect immunoperoxidase method. Of the ten cases of mucinous signet ring cell
      carcinomas 5 showed high, 3 moderate and 2 low tetranectin expression. Of the ten
      cases of well-differentiated intestinal type adenocarcinomas (ITA) 4 showed
      moderate regional, 3 low regional and 3 negative tetranectin expression. Of the
      ten cases of moderately-differentiated ITA 3 showed moderate regional, 4 low
      regional and 3 negative tetranectin expression. Of the ten cases of poorly
      differentiated ITA 4 showed focal low and 6 negative tetranectin expression.
      Overall, the mucinous signet ring carcinomas showed significantly higher
      tetranectin expression compared to ITA (chi2 = 3.95, p<0.05). In contrast, no
      significant relationship was found between tetranectin expression and the degree
      of differentiation in ITA (chi2 = 2.5, p>0.05). In all cases, the perineoplastic
      desmoplastic reactive stroma showed high expression of tetranectin intra- and
      extracellularly. The mast cells and goblet cells in the areas of intestinal
      metaplasia showed high tetranectin expression. CONCLUSIONS: This study shows
      that: a) tetranectin is produced and deposited extracellularly in the
      desmoplastic peritumoral stroma of infiltrating gastric adenocarcinomas; b)
      tetranectin is more highly expressed by the mucinous signet ring cell carcinomas
      compared to ITA; and c) the amount of tetranectin produced by the ITA is
      unrelated with the degree of tumor differentiation.

PMID- 11962753
TI  - Effects of the antirheumatic remedy hox alpha--a new stinging nettle leaf extract
      -on matrix metalloproteinases in human chondrocytes in vitro.
AB  - Inflammatory joint diseases are characterized by enhanced extracellular matrix
      degradation which is predominantly mediated by cytokine-stimulated upregulation
      of matrix metalloproteinase (MMP) expression. Besides tumour necrosis factor
      alpha (TNF-alpha), Interleukin-1beta (IL-1beta) produced by articular
      chondrocytes and synovial macrophages, is the most important cytokine stimulating
      MMP expression under inflammatory conditions. Blockade of these two cytokines and
      their downstream effectors are suitable molecular targets of antirheumatic
      therapy. Hox alpha is a novel stinging nettle (Urtica dioica/Urtica urens) leaf
      extract used for treatment of rheumatic diseases. The aim of the present study
      was to clarify the effects of Hox alpha and the monosubstance 13-HOTrE (13
      Hydroxyoctadecatrienic acid) on the expression of matrix metalloproteinase-1, -3
      and -9 proteins (MMP-1, -3, -9). Human chondrocytes were cultured on collagen
      type-II-coated petri dishes, exposed to IL-1beta and treated with or without Hox
      alpha and 13-HOTrE. A close analysis by immunofluorescence microscopy and western
      blot analysis showed that Hox alpha and 13-HOTrE significantly suppressed IL
      1beta-induced expression of matrix metalloproteinase-1, -3 and -9 proteins on the
      chondrocytes in vitro. The potential of Hox alpha and 13-HOTrE to suppress the
      expression of matrix metalloproteinases may explain the clinical efficacy of
      stinging nettle leaf extracts in treatment of rheumatoid arthritis. These results
      suggest that the monosubstance 13-HOTrE is one of the more active
      antiinflammatory substances in Hox alpha and that Hox alpha may be a promising
      remedy for therapy of inflammatory joint diseases.

PMID- 11962754
TI  - The hepatic stellate cell in the post-genomic era.
AB  - The draft human genome sequence was published on February 15, 2001, which will
      provide a huge amount of information on human genetics, human disease, and human
      cell biology. Now, medical scientists and cell biologists are turning their
      attention to illustrating gene expression pattern using gene microarray and to
      identifying the functions and the expression patterns of proteins encoded by the
      genes. Hepatic stellate cell is one of the sinusoid-constituent cells that play
      multiple roles in the liver pathophysiology. Transformation of stellate cells
      from the vitamin A-storing phenotype to the "myofibroblastic" one closely
      correlates to hepatic fibrosis during chronic liver trauma. Analyses of the
      molecular mechanisms of stellate cell activation have made a great progress, in
      particular, in the field of intracellular signal transduction of transforming
      growth factor-beta and platelet-derived growth factor, integrin signaling related
      to cell-adhesion, and cell motility-associated Rho and focal-adhesion kinase.
      Accumulation of the information on the stellate cell activation would shed light
      on the establishment of a novel therapeutic strategy against fibrosis of human
      liver disease.

PMID- 11962755
TI  - Low density lipoproteins and mitogenic signal transduction processes: role in the
      pathogenesis of renal disease.
AB  - Abnormalities in lipid and lipoprotein metabolism are commonly observed in
      patients with chronic renal disease. Specifically, hyperlipidemia and the
      glomerular deposition of atherogenic lipoproteins (e.g., Low density lipoprotein,
      LDL; and its oxidized variants) are implicated in key pathobiological processes
      involved in the development of glomerular disease, including stimulation of
      monocyte infiltration into the mesangial space, mesangial cell hypercellularity,
      and mesangial extracellular matrix deposition. This review discusses recent
      understanding of glomerular mitogenic responses, intracellular signaling events
      associated with mesangial hypercellularity in renal diseases, and the
      participation of cholesterol and atherogenic lipoproteins in intracellular
      signaling pathways involved in mesangial cell proliferation. Generally, the
      mitogenic intracellular signaling pathways are regulated by the activation of
      series of transmembrane and cytoplasmic protein tyrosine kinases that converge
      into the activation of Ras and down-stream mitogen-activated protein kinase (MAP
      kinase). Activated MAP kinase, through translocating into the nucleus and the
      activation of various transcription factors and protooncogenes, regulate cell
      proliferation. The importance of mitogenic intracellular signaling in mesangial
      proliferative disease has only recently been recognized and showed that the
      activation of MAP kinase and/or cyclin/cyclin-dependent kinases play crucial role
      in different phases of cell growth cycle and hypercellularity of glomerular cells
      in various experimental renal diseases. Using glomerular mesangial cells as an in
      vitro model system, studies from our laboratory indicated that the accumulation
      of LDL and more potently its oxidized forms within the glomerulus, through the
      activation of membrane receptor tyrosine kinases (e.g., EGF receptor), activate
      Ras and MAP kinase signaling cascade leading to DNA synthesis and subsequent
      mesangial cell proliferation. These data suggest that atherogenic lipoproteins
      may act as one of the major endogenous modulators for mitogenic signaling
      response and cell proliferation within the glomerulus. It is reasonable to
      speculate that the correction or reduction of hyperlipidemia, glomerular lipid
      deposition, and the pro-oxidative milieu within the glomerulus, through the
      inhibition of mitogenic signaling events, may provide protective environment
      against mesangial hypercellularity and subsequent matrix deposition, and the
      progression of renal disease.

PMID- 11962756
TI  - CD34+ stem cells in chronic myeloproliferative disorders.
AB  - Contrasting the wealth of information that is available about various biological
      and therapeutic aspects of human CD34+ stem cells, little data exist concerning
      their quantity and dynamics as well as their mutual relationships with other
      hematopoietic constituents in the bone marrow of patients with chronic
      myeloproliferative disorders. In comparison with a control group frequency of
      progenitors is significantly increased in chronic myeloid leukemia (CML).
      Following different therapeutic modalities their quantity reflects therapeutic
      efficacy (responder and non-responder patients) and therefore exerts a predictive
      value regarding acceleration and blastic crisis. The significant correlations
      between fiber content and number of these precursors elucidates the complex
      interactions between stroma and progenitor cell differentiation and maturation.
      Following allogeneic bone marrow transplantation there is a rapid recovery of the
      CD34+ stem cell population in the first month. A higher number of these cells is
      related with graft size, an earlier independence for platelet transfusion and a
      more extended regeneration of erythro- and megakaryopoiesis. The slight increase
      in reticulin fibers in these patients may be associated with the complex and so
      far ill-defined pathomechanism of homing (adherence to the fibrous matrix). In
      idiopathic myelofibrosis (IMF) an increased number of CD34+ stem cells is found
      predominantly in the early (prefibrotic or mild fibrotic) hypercellular stages
      and probably indicates a higher proliferative activity of the precursor cell
      pool. According to sequential biopsies most patients with early IMF that later
      evolved into an overt fibrosclerotic stage usually display a reduction of
      progenitor cells during the development of myelofibrosis. The unequal
      distribution of CD34+ stem cells in the bone marrow versus spleen in IMF
      (advanced fibrosclerotic stage) is in support of the currently discussed
      hypothesis of splenic filtration and concentration of precursor cells as an
      essential feature of myeloid metaplasia. Regarding prognosis in CML a higher
      amount of CD34+ stem cells is significantly associated with an unfavorable
      survival and thus confirms the assumed implication of an accelerated phase of
      disease at onset. On the other hand, in polycythemia vera (PV) and IMF a low
      number of progenitors is probably due to a decreased proliferation rate (reduced
      hematopoietic turnover index) and therefore reflects a reduction in the
      regenerative capacity of hematopoiesis. For this reason, a presumptive defect in
      the recovery of normal and clonally transformed stem cells is speculated to add
      to the worsening of prognosis by causing the well-known bone marrow insufficiency
      in terminal stage PV and IMF.

PMID- 11962757
TI  - The cellular matrix: a feature of tensile bearing dense soft connective tissues.
AB  - The term connective tissue encompasses a diverse group of tissues that reside in
      different environments and must support a spectrum of mechanical functions.
      Although the extracellular matrix of these tissues is well described, the
      cellular architecture of these tissues and its relationship to tissue function
      has only recently become the focus of study. It now appears that tensile-bearing
      dense connective tissues may be a specific class of connective tissues that
      display a common cellular organization characterized by fusiform cells with
      cytoplasmic projections and gap junctions. These cells with their cellular
      projections are organised into a complex 3-dimensional network leading to a
      physically, chemically and electrically connected cellular matrix. The cellular
      matrix may play essential roles in extracellular matrix formation, maintenance
      and remodelling, mechanotransduction and during injury and healing. Thus, it is
      likely that it is the interaction of both the extracellular matrix and cellular
      matrix that provides the basis for tissue function. Restoration of both these
      matrices, as well as their interaction must be the goal of strategies to repair
      these connective tissues damaged by either injury or disease.

PMID- 11962758
TI  - Natural killer cell malignancies: clinicopathologic and molecular features.
AB  - Malignancies of natural killer (NK) cells have increasingly been recognized as
      distinct clinicopathological entities. The tumor cells are characterized by an
      immunophenotype of CD2+, surface CD3-, cytoplasmic CD3epsilon+, and CD56+. The T
      cell receptor gene is in germline configuration, and a consistent association
      with Epstein-Barr virus is demonstrable. Pathologically, the tumor cells show
      variable cytological appearances, with frequent angioinvasion and angiocentricity
      associated with zonal necrosis. Clinically, most cases affect the nasal cavity or
      other parts of the upper aerodigestive tract, and are referred to as nasal NK
      cell lymphoma. A minority involve extranasal sites such as the skin,
      gastrointestinal tract and testis, and are often referred to as extranasal NK
      cell lymphoma. A particularly aggressive form presents fulminantly as
      disseminated disease, sometimes with a leukemic phase, and is referred to as
      aggressive NK cell lymphoma/leukemia. Cytogenetic and molecular analysis have
      shown DNA losses at chromosomes 6q, 11q, 13q and 17p to be recurrent aberrations
      in NK cell malignancies. Frequent DNA gains are also found in chromosomes 1p, 6p,
      11q, 12q, 17q, 19p, 20q, and Xp. These regions of DNA losses and gains should be
      targets for further investigation in order to understand the molecular
      pathogenesis of this lymphoma. Finally, optimal treatment modalities need to be
      determined, as all subtypes of NK cell malignancies are associated with a poor
      prognosis.

PMID- 11962759
TI  - Nonvisual photoreceptors of the deep brain, pineal organs and retina.
AB  - The role of the nonvisual photoreception is to synchronise periodic functions of
      living organisms to the environmental light periods in order to help survival of
      various species in different biotopes. In vertebrates, the so-called deep brain
      (septal and hypothalamic) photoreceptors, the pineal organs (pineal- and
      parapineal organs, frontal- and parietal eye) and the retina (of the "lateral"
      eye) are involved in the light-based entrain of endogenous circadian clocks
      present in various organs. In humans, photoperiodicity was studied in connection
      with sleep disturbances in shift work, seasonal depression, and in jet-lag of
      transmeridional travellers. In the present review, experimental and molecular
      aspects are discussed, focusing on the histological and histochemical basis of
      the function of nonvisual photoreceptors. We also offer a view about functional
      changes of these photoreceptors during pre- and postnatal development as well as
      about its possible evolution. Our scope in some points is different from the
      generally accepted views on the nonvisual photoreceptive systems. The deep brain
      photoreceptors are hypothalamic and septal nuclei of the periventricular
      cerebrospinal fluid (CSF)-contacting neuronal system. Already present in the
      lancelet and representing the most ancient type of vertebrate nerve cells
      ("protoneurons"), CSF-contacting neurons are sensory-type cells sitting in the
      wall of the brain ventricles that send a ciliated dendritic process into the CSF.
      Various opsins and other members of the phototransduction cascade have been
      demonstrated in telencephalic and hypothalamic groups of these neurons. In all
      species examined so far, deep brain photoreceptors play a role in the circadian
      and circannual regulation of periodic functions. Mainly called pineal "glands" in
      the last decades, the pineal organs actually represent a differentiated form of
      encephalic photoreceptors. Supposed to be intra- and extracranially outgrown
      groups of deep brain photoreceptors, pineal organs also contain neurons and glial
      elements. Extracranial pineal organs of submammalians are cone-dominated
      photoreceptors sensitive to different wavelengths of light, while intracranial
      pineal organs predominantly contain rod-like photoreceptor cells and thus
      scotopic light receptors. Vitamin B-based light-sensitive cryptochromes localized
      immunocytochemically in some pineal cells may take part in both the
      photoreception and the pacemaker function of the pineal organ. In spite of
      expressing phototransduction cascade molecules and forming outer segment-like
      cilia in some species, the mammalian pineal is considered by most of the authors
      as a light-insensitive organ. Expression of phototransduction cascade molecules,
      predominantly in young animals, is a photoreceptor-like characteristic of
      pinealocytes in higher vertebrates that may contribute to a light-percepting task
      in the perinatal entrainment of rhythmic functions. In adult mammals, adrenergic
      nerves--mediating daily fluctuation of sympathetic activity rather than retinal
      light information as generally supposed--may sustain circadian periodicity
      already entrained by light perinatally. Altogether three phases were supposed to
      exist in pineal entrainment of internal pacemakers: an embryological
      synchronization by light and in viviparous vertebrates by maternal effects (1); a
      light-based, postnatal entrainment (2); and in adults, a maintenance of
      periodicity by daily sympathetic rhythm of the hypothalamus. In addition to its
      visual function, the lateral eye retina performs a nonvisual task. Nonvisual
      retinal light perception primarily entrains genetically-determined periodicity,
      such as rod-cone dominance, EEG rhythms or retinomotor movements. It also
      influences the suprachiasmatic nucleus, the primary pacemaker of the brain. As
      neither rods nor cones seem to represent the nonvisual retinal photoreceptors,
      the presence of additional photoreceptors has been supposed. Cryptochrome 1, a
      photosensitive molecule identified in retinal nerve cells and in a subpopulation
      of retinal photoreceptors, is a good candidate for the nonvisual photoreceptor
      molecule as well as for a member of pacemaker molecules in the retina. When
      comparing various visual and nonvisual photoreceptors, transitory, "semi visual"
      (directional) light-perceptive cells can be detected among them, such as those in
      the parietal eye of reptiles. Measuring diffuse light intensity of the
      environment, semivisual photoreceptors also possess some directional light
      perceptive capacity aided by complementary lens-like structures, and screening
      pigment cells. Semivisual photoreception in aquatic animals may serve for
      identifying environmental areas of suitable illumination, or in poikilotermic
      terrestrial species for measuring direct solar irradiation for thermoregulation.
      As directional photoreceptors were identified among nonvisual light perceptive
      cells in the lancelet, but eyes are lacking, an early appearance of semivisual
      function, prior to a visual one (nonvisual --> semivisual --> visual?) in the
      vertebrate evolution was supposed.

PMID- 11962760
TI  - Perivascular nerves and vascular endothelium: recent advances.
AB  - Within the last few years, advances have been made regarding perivascular nerves
      and the endothelium of the vascular system, both potentially important in the
      understanding of the mechanisms of local control of blood flow. Endothelin-1 (ET
      1) has been identified in rat cerebrovascular nerves, neuropeptide Y (NPY) has
      been demonstrated in umbilical endothelium, the arginine-vasopressin (VP) system
      has been discovered in the heart (including coronary endothelium), and P2X
      receptors have been observed in vascular endothelial cells. After a brief
      introduction to vascular biology, this review will focus on the above-mentioned
      new data.

PMID- 11962761
TI  - Tumor-associated fibroblasts (part I): Active stromal participants in tumor
      development and progression?
AB  - Phenotypic and functional characteristics of tumor associated fibroblasts (TAF)
      in contrast to normal fibroblasts are reviewed in this first synopsis (part I).
      Terms as tumor stroma, desmo-plasia, TAF, myofibroblast, and fetal-type
      fibroblast are defined, and experimental systems to study heterologous cell
      interactions are presented. While we only start to gather information on the
      genotype of TAF, a broad range of data deals with the expression profile of these
      cells, covering e.g. ECM and ECM-modulating molecules, growth factors and
      cytokines. Summarizing the recent state of knowledge indicates that TAF provide
      sources for tumor diagnosis and therapy, that have to be further defined in an
      organ-specific approach in terms of the functional impact on the tumor cell and
      its environment (see part II).

PMID- 11962762
TI  - Tumor-associated fibroblasts (part II): Functional impact on tumor tissue.
AB  - The article focuses on the functional impact of tumor-associated fibroblasts
      (TAF) on its surrounding cells. It intends to cover the recent knowledge on TAF,
      the phenotype, and expression profile of which have been described in the first
      part of the review series (Kunz-Schughart and Knuechel, 2002). The present review
      is subdivided into two main chapters: (1) functional impact of TAF on tumor cells
      and (2) fibroblast-host cell interactions in tumor tissue. In the first paragraph
      of chapter (1) about the role of fibroblasts in tumor cell growth and
      differentiation it is revealed, how strongly cellular interaction is dependent on
      fibroblast and tumor cell type as well as the spatial ratio between the cells.
      The variation of cellular behavior depending on quantity of molecules holds also
      true for the group of ECM molecules, e.g. the balance between MMPs and TIMPs,
      which provide an interesting therapeutic target in tumor tissue. This is one of
      the topics addressed in the second paragraph which focuses on tumor cell
      dissemination. Chapter (2) addresses the relation of TAF to other intra- or
      peritumoral host cells. The hypoxia-related angiogenesis induction of fibroblasts
      via growth factor secretion (e.g. VEGF) is considered as important as the immune
      modulatory properties of fibroblasts on immune cells, such as
      monocytes/macrophages. These cellular properties can be tested under controlled
      conditions in three-dimensional heterologous cultures of human cells, providing
      the chance for systematic modification to assess therapeutic effects in an in
      vivo like environment.

PMID- 11962763
TI  - Counting particles in tissue sections: choices of methods and importance of
      calibration to minimize biases.
AB  - Investigators must choose between counting methods to quantify microscopic
      particles in tissues. The conventional profile-based ("model-based" or "2D-")
      counting methods have been criticized for their potential biases due to
      assumptions about shapes, sizes, and orientation of particles when converting
      profile counts into cell numbers. New stereological methods ("design-based" or
      "3D-") methods such as the optical disector or physical disector were initially
      introduced as being inherently unbiased. Recent calibration analyses and
      comparisons of results from different investigators have revealed the potential
      for significant biases in the most efficient and most frequently used design
      based method, the optical disector. This review aims to objectively assess the
      strengths and limitations of current profile- and disector-based cell counting
      methods by examination of studies in which these methods have been calibrated
      against the "gold-standard", counts obtained by 3-dimensional reconstruction of
      serial sections. Advantages and disadvantages of each counting method and the
      associated embedding and sectioning techniques are compared and frequent mistakes
      and pitfalls of each technique are discussed. The importance of a calibration
      step for each technique is emphasized, and a protocol is provided for a quick and
      simple calibration by a "sampling" 3-D reconstruction of limited serial sections.
      Trends in the usage of counting methods are analyzed in four major journals. It
      is hoped that this review will be helpful, for both investigators and manuscript
      reviewers, in clarifying some of the contentious issues in the choice and
      implementation of appropriate methods for particle counting in tissue sections.

PMID- 11962764
TI  - Membrane electropermeabilization effects of frequency and membrane surface order
      on liposome leakage.
AB  - Liposomes containing fluorescence marker were exposed to an alternating electric
      field of 80 V peak to peak square electric waves at different frequencies 0.01,
      1, and 100 kHz to perturb the liposome permeation. The efflux of fluorescence dye
      after application of the electric field was measured by recording the
      fluorescence emission due to the complex formation reaction between the
      fluorescence dye and calcium ions in the bulk medium solution. Two independent
      sets of experiments were conducted: 1) calcium ions were present during
      electropulsation; and 2) they were added after electric field application. Two
      parameters, fluorescence emission intensity and increment of temperature of the
      solution in the chamber, were studied. The effect of membrane surface order on
      the fluorescence dye leakage from the liposomes was studied by addition of urea
      at threshold concentration before the liposomes sealed. The data demonstrate the
      existence of frequency dependency window at 1 kHz. Furthermore, the data were
      interpreted according to the theory of interactions of electromagnetic fields
      with highly polarized and deformed materials such as liposome particles. The urea
      caused an enhancement of the fluorescence dye leakage at frequency of 100 kHz.
      This effect could be explained as a decrease of the membrane binding rigidity due
      to the disordering effect of urea on the membrane lipid surface. Our conclusion
      is that the frequency and the membrane surface order are additional parameters
      that influence the processes of membrane electropermeabilization.

PMID- 11962765
TI  - The versatile functions of the transcriptional coactivators p300 and CBP and
      their roles in disease.
AB  - p300 and CBP are highly homologous coactivators which promote gene transcription
      by bridging between DNA-binding transcription factors and the basal transcription
      machinery, by providing a scaffold for integrating transcription factors, and by
      modifying transcription factors and chromatin through acetylation. The p300/CBP
      cofactors are involved in a plethora of physiological processes, and their
      activity is essential for embryogenesis. Chromosomal translocations affecting the
      p300 and Cbp genes are the cause of hematological malignancies, and Cbp
      haploinsufficiency is a hallmark of the Rubinstein-Taybi syndrome. In addition,
      mutations in the Cbp or p300 gene, accompanied by loss of the other allele, have
      been found in various kinds of tumors. Furthermore, inhibition of CBP and p300
      function in neurodegenerative diseases caused by polyglutamine expansion may be
      an underlying cause for cytotoxicity. Approaches to modulate p300/CBP function
      may be instrumental in the development of novel therapies directed against viral
      infections, cancer and neurodegenerative diseases.

PMID- 11962766
TI  - Survivin--a universal tumor antigen.
AB  - Tumor-associated antigens recognized by cellular effectors of the immune system
      are potential targets for antigen-specific cancer immunotherapy. These antigens
      are classified as tissue (melanocyte)-specific proteins, cancer-testis antigens
      (proteins expressed in normal testis and various cancers), tumor-specific
      peptides derived from mutations in tumor cells, and others. Clinical studies with
      peptides and proteins derived from these antigens have been initiated to study
      the efficacy of inducing specific cytotoxic T lymphocytes (CTL) responses in
      vivo. However, most of the peptide epitopes used in these vaccination trials are
      melanocyte-specific, and these peptides cannot be applied for tumors of non
      melanocyte origin. Furthermore, the expression of most tumor antigens is
      heterogeneous among tumors from different patients and can even vary among
      metastases obtained from one patient. Immune selection of antigen loss variants
      may prove to be an additional obstacle for the clinical applicability of most of
      the known CTL epitopes. Recently, a new tumor antigen, survivin, has been
      identified on the basis of spontaneous CTL responses in different cancer
      patients. Survivin is expressed in most human neoplasms, but not in normal,
      differentiated tissues. Importantly, downregulation or loss of survivin would
      severely inflict the growth potential of the tumor cell. Since survivin is
      expressed by a variety of different tumors MHC-restricted survivin epitopes may
      serve as important and widely applicable targets for anti-cancer
      immunotherapeutic strategies.

PMID- 11962768
TI  - Biological basis of hearing-aid design.
AB  - We show that we can accurately model the auditory-nerve discharge patterns in
      response to sounds as complex as speech and ask how we may exploit this knowledge
      to test new strategies for hearing-aid signal processing. We describe the
      auditory-nerve representations of vowels in normal and noise-damaged ears. The
      normal representations are predicted well by a cochlear signal processing model
      originally developed by Carney (Carney, L. H. J. Acoust. Soc. Am. 93:401-417,
      1993). Basilar-membrane tuning is represented by a time-varying narrow-band
      filter. Outer hair cell control of tuning is exerted by a nonlinear feedback
      path. We show that the effects of noise-induced outer hair cell damage can be
      modeled by scaling the feedback signal appropriately and use the model to test
      one strategy for hearing-aid speech processing. We conclude by discussing some
      aspects of future trends in biomedical engineering approaches to problems of
      hearing impairment.

PMID- 11962767
TI  - Intergenic mRNAs. Minor gene products or tools of diversity?
AB  - The general model of gene expression implies that the units of genetic
      information, the genes, constitute the basis of the mRNA and protein products
      detected in living organisms. It is well known that in eukaryotic cells a single
      gene may give rise to various gene products due to alternative splicing and/or
      different positions of transcriptional start and termination. However, recent
      experimental results suggest that in addition to this variation in gene
      expression, another level of complexity may also exist as evidence for the
      presence of mRNAs that combine sequence information (exons) from distinct genes
      is accumulating. Moreover, the mechanisms that allow this production of
      intergenic mRNAs are starting to unravel and it appears that these follow two
      general pathways: (a) bypass of transcriptional termination, resulting in the
      generation of bicistronic pre-mRNAs; and (b) authentic trans-splicing events
      between pre-mRNAs of distinct genes.

PMID- 11962769
TI  - Measuring the electrical stapedius reflex with stapedius muscle electromyogram
      recordings.
AB  - Previous studies have demonstrated a correlation between cochlear implant
      recipients' comfort levels (C level, upper limit of dynamic range of stimulation)
      and the contralateral electrical stapedius reflex (ESR) threshold, detected by
      acoustic impedance change. However, the utility of the approach is limited
      because many recipients have no detectable impedance change. The goals of this
      study were to investigate the utility of the stapedial electromyogram (EMG) for
      estimating onset and strength of the ESR. Ketamine-anesthetized guinea pigs were
      implanted with Nucleus electrode arrays and stimulated with biphasic current
      pulse trains (250 pps) via a Cochlear Corporation CI24M stimulator. Typical EMG
      recordings (obtained with bipolar microwire electrodes) contained easily
      detectable unit potentials up to 300 microV in amplitude. Growth response curves
      (obtained from threshold-crossing counts or rms of the EMG signal) were typically
      monotonic with dynamic ranges spanning 700 microA or 8 dB. Based on adaptation
      and temporal properties, the stimulus protocol (500 ms duration with 4-5 s
      interstimulus intervals) was adequate for producing independent responses. The
      data presented are consistent with ESR characteristics (acoustic impedance
      technique) of cochlear implant recipients and with EMG properties of acoustically
      stimulated guinea pigs. Use of the EMG for characterizing the ESR may eventually
      be applied to human cochlear implant recipients as a guide in setting the upper
      limit of the dynamic range.

PMID- 11962770
TI  - Intelligent multichannel stimulator for the study of cardiac arrhythmias.
AB  - An intelligent multichannel stimulator (IMS) has been designed and built for use
      in a cardiac research environment. The device is capable of measuring and
      responding to cardiac electrophysiological phenomena in real time with carefully
      timed and placed electrical stimuli. The system consists of 16 channels of
      sense/stimulation electronics controlled by a digital signal processor (DSP) data
      acquisition card and a host computer and can be expanded to include more
      channels. The DSP allows for powerful and flexible algorithms to be implemented
      for real-time interaction with the cardiac tissue. Although a number of possible
      uses can be conceived for such a device, the initial motivation was to improve
      upon attempts to terminate fibrillation by pacing. The IMS was tested in an open
      chest animal model, both in sinus rhythm and during fibrillation. It was shown to
      be an effective research tool by demonstrating the ability to measure and respond
      to cardiac activations in real time using complex numerical algorithms and
      appropriately timed stimuli.

PMID- 11962771
TI  - A stochastic nonlinear autoregressive algorithm reflects nonlinear dynamics of
      heart-rate fluctuations.
AB  - Current methods for detecting nonlinear determinism in a time series require long
      and stationary data records, as most of them assume that the observed dynamics
      arise only from the internal, deterministic workings of the system, and the
      stochastic portion of the signal (the noise component) is assumed to be
      negligible. To explicitly account for the stochastic portion of the data we
      recently developed a method based on a stochastic nonlinear autoregressive (SNAR)
      algorithm. The method iteratively estimates nonlinear autoregressive models for
      both the deterministic and stochastic portions of the signal. Subsequently, the
      Lyapunov exponents (LE) are calculated for the estimated models in order to
      examine if nonlinear determinism is present in the deterministic portion of the
      fitted model. To determine if nonlinear dynamic analysis of heart-rate
      fluctuations can be used to assess arrhythmia susceptibility by predicting the
      outcome of invasive cardiac electrophysiologic study (EPS), we applied the SNAR
      algorithm to noninvasively measured resting sinus-rhythm heart-rate signals
      obtained from 16 patients. Our analysis revealed that a positive LE was highly
      correlated to a patient with a positive outcome of EPS. We found that the
      statistical accuracy of the SNAR algorithm in predicting the outcome of EPS was
      88% (sensitivity=100%, specificity=75%, positive predictive value=80%, negative
      predictive value=100%, p=0.0019). Our results suggest that the SNAR algorithm may
      serve as a noninvasive probe for screening high-risk populations for malignant
      cardiac arrhythmias.

PMID- 11962772
TI  - Mechanistic model of myocardial energy metabolism under normal and ischemic
      conditions.
AB  - A moderate reduction in coronary blood flow results in decreased myocardial
      oxygen consumption, accelerated glycolysis, decreased pyruvate oxidation, and
      lactate accumulation. To quantitatively understand cardiac metabolism during
      ischemia, we have developed a mechanistic, mathematical model based on
      biochemical mass balances and reaction kinetics in cardiac cells. By numerical
      solution of model equations, computer simulations showed the dynamic responses in
      glucose, fatty acid, glucose-6-phosphate, glycogen, triglyceride, pyruvate,
      lactate, acetyl-CoA, and free-CoA as well as CO2, O2, phosphocreatine/creatine,
      nicotinamide adenine dinucleotide (reduced form)/nicotinamide adenine
      dinucleotide (oxidized form) (NADH/NAD+), and adenosine diphosphate/adenosine
      triphosphate (ADP/ATP). When myocardial ischemia was simulated by a 60% reduction
      in coronary blood flow, the model generated myocardial concentrations, uptakes,
      and fluxes that were consistent with experimental data from in vivo pig studies.
      After 60 min of ischemia the concentrations of glycogen, phosphocreatine, and ATP
      were decreased by 60%, 75%, and 50%, respectively. With the onset of ischemia,
      myocardial lactate concentration increased and the myocardium switched from net
      consumer to net producer of lactate. Our model predicted a rapid 13-fold increase
      in NADH/NAD+, but only a twofold increase in the ratio of acetyl-CoA to free-CoA.
      These findings are consistent with the concept that pyruvate oxidation is
      inhibited during ischemia partially by the rise in NADH/NAD+.

PMID- 11962773
TI  - Prestress due to dimensional changes caused by demineralization: a potential
      mechanism for microcracking in bone.
AB  - Microcracking in bone due to internal strains caused by mineralization is a
      possible mechanism of damage. Similar damage can be seen in other biological
      composites such as trees experiencing growth-related prestresses. Dimensional
      changes in cortical bone due to demineralization and experimental glycation were
      studied to test whether mineralization-related prestrains are consistent with
      observed microcracking patterns in bone. A microscopy technique that enables wet
      measurements of length and angle of milled bone specimens was used.
      Demineralization of bovine and human bones caused significant anisotropic changes
      in tissue size. Dimensional changes due to demineralization in bovine bone were
      prevented or reduced when collagen cross linking was increased by glycation. The
      dimensional changes of bone caused by demineralization are consistent with the
      hypothesis that mineralization-caused stresses in remodeling tissue can cause
      microcracks.

PMID- 11962774
TI  - Vibratory coherence as an alternative to radiography in assessing bone healing
      after osteodistraction.
AB  - Distraction osteogenesis is used in orthopedics to lengthen bones by cutting or
      breaking the bone and gradually separating the two pieces as new bone fills the
      intervening space. There is a need for early assessment of the degree of bone
      healing that allows for normal functioning without unwanted side effects. This
      study compared different techniques used to evaluate the degree of bone healing
      during mandibular osteodistraction in 21 rabbits. For each rabbit, the mandible
      was cut in a surgical procedure and then 72 h later distraction began at a rate
      of 3 mm per day. Bone formation at the distraction site was assessed by in vivo
      photodensitometry on head radiographs, an in vivo (nondestructive) vibratory
      coherence test across the distraction site, a postmortem, ex vivo (destructive)
      three-point bending mechanical test, and by postmortem, ex vivo (destructive)
      histological examination. Statistical analyses included analysis of variance and
      correlation coefficient tests. The findings revealed that the results of bone
      photodensity and the mechanical three-point test are highly and positively
      correlated with the results of the vibration test. The use of the vibration test
      may provide a substitute for or augment the routine use of radiography for in
      vivo evaluation and monitoring of bone healing.

PMID- 11962775
TI  - Mathematical model of diffusion-limited gas bubble dynamics in unstirred tissue
      with finite volume.
AB  - Models of gas bubble dynamics for studying decompression sickness have been
      developed by considering the bubble to be immersed in an extravascular tissue
      with diffusion-limited gas exchange between the bubble and the surrounding
      unstirred tissue. In previous versions of this two-region model, the tissue
      volume must be theoretically infinite, which renders the model inapplicable to
      analysis of bubble growth in a finite-sized tissue. We herein present a new two
      region model that is applicable to problems involving finite tissue volumes. By
      introducing radial deviations to gas tension in the diffusion region surrounding
      the bubble, the concentration gradient can be zero at a finite distance from the
      bubble, thus limiting the tissue volume that participates in bubble-tissue gas
      exchange. It is shown that these deviations account for the effects of
      heterogeneous perfusion on gas bubble dynamics, and are required for the tissue
      volume to be finite. The bubble growth results from a difference between the
      bubble gas pressure and an average gas tension in the surrounding diffusion
      region that explicitly depends on gas uptake and release by the bubble. For any
      given decompression, the diffusion region volume must stay above a certain
      minimum in order to sustain bubble growth.

PMID- 11962776
TI  - Numerical simulation of the influence of gravity and posture on cardiac
      performance.
AB  - A numerical model of the cardiovascular system was used to quantify the
      influences on cardiac function of intrathoracic pressure and intravascular and
      intraventricular hydrostatic pressure, which are fundamental biomechanical
      stimuli for orthostatic response. The model included a detailed arterial
      circulation with lumped parameter models of the atria, ventricles, pulmonary
      circulation, and venous circulation. The venous circulation was divided into
      cranial, central, and caudal regions with nonlinear compliance. Changes in
      intrathoracic pressure and the effects of hydrostatic pressure were simulated in
      supine, launch, sitting, and standing postures for 0, 1, and 1.8 G. Increasing
      intrathoracic pressure experienced with increasing gravity caused 12% and 14%
      decreases in cardiac output for 1 and 1.8 G supine, respectively, compared to 0
      G. Similar results were obtained for launch posture, in which the effects of
      changing intrathoracic pressure dominated those of hydrostatic pressure. Compared
      to 0 G, cardiac output decreased 0.9% for 1 G launch and 15% for 1.8 G launch. In
      sitting and standing, the position of the heart above the hydrostatic
      indifference level caused the effects of changing hydrostatic pressure to
      dominate those of intrathoracic pressure. Compared to 0 G, cardiac output
      decreased 13% for 1 G sitting and 23% for 1.8 G sitting, and decreased 17% for 1
      G standing and 31% for 1.8 G standing. For a posture change from supine to
      standing in 1 G, cardiac output decreased, consistent with the trend necessary to
      explain orthostatic intolerance in some astronauts during postflight stand tests.
      Simulated lower body negative pressure (LBNP) in 0 G reduced cardiac output and
      mean aortic pressure similar to I G standing, suggesting that LBNP provides at
      least some cardiovascular stimuli that may be useful in preventing postflight
      orthostatic intolerance. A unifying concept, consistent with the Frank-Starling
      mechanism of the heart, was that cardiac output was proportional to cardiac
      diastolic transmural pressure for all postures and gravitational accelerations.

PMID- 11962777
TI  - Algorithm for vector autoregressive model parameter estimation using an
      orthogonalization procedure.
AB  - We review the derivation of the fast orthogonal search algorithm, first proposed
      by Korenberg, with emphasis on its application to the problem of estimating
      coefficient matrices of vector autoregressive models. New aspects of the
      algorithm not previously considered are examined. One of these is the application
      of the algorithm to estimate coefficient matrices of a vector autoregressive
      process with time-varying coefficients when multiple realizations of the said
      process are available. Computer simulations were also performed to characterize
      the statistical properties of the estimates. The results show that even for
      shorter time series the algorithm works well and obtains good estimates of the
      time-varying parameters. Statistical characterization indicates that the standard
      deviation of the estimates decreases as 1 square root N (N being the length of
      the time series), a typical behavior of least-squares estimators. Another key
      aspect of the approach, which has previously been considered, is its direct
      extension to the parameter estimation of vector nonlinear autoregressive models.
      Nonlinear terms can be added to the model and the same algorithm can be applied
      to effectively estimate their associated parameters. Using chaotic time series
      generated from the Lorenz equations, the algorithm produces a model that captures
      the nonlinear structure of the data and exhibits the same chaotic attractor as
      that of the original system.

PMID- 11962778
TI  - Modeling of nonlinear physiological systems with fast and slow dynamics. I.
      Methodology.
AB  - Effective modeling of nonlinear dynamic systems can be achieved by employing
      Laguerre expansions and feedforward artificial neural networks in the form of the
      Laguerre-Volterra network (LVN). This paper presents a different formulation of
      the LVN that can be employed to model nonlinear systems displaying complex
      dynamics effectively. This is achieved by using two different filter banks,
      instead of one as in the original definition of the LVN, in the input stage and
      selecting their structural parameters in an appropriate way. Results from
      simulated systems show that this method can yield accurate nonlinear models of
      Volterra systems, even when considerable noise is present, separating at the same
      time the fast from the slow components of these systems effectively.

PMID- 11962779
TI  - Mental health nursing. Secure hospitals 'no place for women'.

PMID- 11962781
TI  - Disaster planning. The day the world blew up.

PMID- 11962780
TI  - Kevin Cobb trial. I helped to convict a rapist and killer.

PMID- 11962782
TI  - Pre-menstrual syndrome. The violent curse of East Enders' Jackie.

PMID- 11962787
TI  - Milking the NHS dry.

PMID- 11962783
TI  - Should nursing lecturers work on the wards to maintain credibility?

PMID- 11962788
TI  - Health care assistants. Trading places.

PMID- 11962790
TI  - How would you change the NHS?

PMID- 11962789
TI  - Behcet's syndrome. Wise after the event.

PMID- 11962791
TI  - Stirred but not shaken.

PMID- 11962792
TI  - Is it right to collude in a patient's delusion?

PMID- 11962793
TI  - Resources for better practice. Telephone intervention in mental health nursing.

PMID- 11962794
TI  - Best practice in barium enemas.

PMID- 11962795
TI  - Osteoporosis: cause and treatment.

PMID- 11962796
TI  - Falling through the gap: physically ill parents.

PMID- 11962797
TI  - Smoothing the way to improved care. Interview by Jenine Willis.

PMID- 11962798
TI  - Communication and lifelong learning.

PMID- 11962800
TI  - Recording a 12-lead electrocardiogram--3.

PMID- 11962801
TI  - You can see it in their eyes.

PMID- 11962808
TI  - Rehabilitation. Head and shoulders above the rest.

PMID- 11962809
TI  - Mobile phones. Health costs of kids' calls.

PMID- 11962810
TI  - Prison health care. Crash landing for high ideals.

PMID- 11962811
TI  - HIV/AIDS. Why Manchester has got the right idea.

PMID- 11962812
TI  - Pilot light that refuses to go out.

PMID- 11962813
TI  - Tribunal. Storm blows over for 'sea' nurse.

PMID- 11962814
TI  - Should smokers and fat people pay more for the NHS?

PMID- 11962820
TI  - Down with Dr Mumble.

PMID- 11962821
TI  - A hard day's night.

PMID- 11962822
TI  - While you were sleeping.

PMID- 11962823
TI  - Dr No.

PMID- 11962825
TI  - The role of practice nurse trainers in raising standards within PCGs.

PMID- 11962827
TI  - What is the future of clinical leadership?

PMID- 11962824
TI  - The management of glue ear.

PMID- 11962828
TI  - Hysterectomy: nursing the physical and emotional wounds.

PMID- 11962829
TI  - Exploring normal anatomy and physiology. Heart failure--3.

PMID- 11962830
TI  - Lonely planet.

PMID- 11962835
TI  - Overwhelmed down under.

PMID- 11962836
TI  - Return to nursing. Swimming against the tide.

PMID- 11962837
TI  - Nurses take on police surgeon roles in ground-breaking scheme.

PMID- 11962838
TI  - Nurses failing to spot malnourished patients.

PMID- 11962839
TI  - Larval therapy. World's smallest surgeons with appetite for work.

PMID- 11962840
TI  - Mental health nursing. Care in the community 'has not been a failure', say MPs.

PMID- 11962841
TI  - Have standards of care improved over the last 25 years?

PMID- 11962842
TI  - Life and death decisions.

PMID- 11962843
TI  - Time to halt the brain drain in children's mental health.

PMID- 11962844
TI  - Outreach care is essential to free up beds.

PMID- 11962845
TI  - Alcoholism is an illness, not a lifestyle choice.

PMID- 11962846
TI  - Cruelty is not gender specific.

PMID- 11962847
TI  - Give mental health patients a sporting chance.

PMID- 11962848
TI  - Neglected subjects.

PMID- 11962849
TI  - The mother of all nurses.

PMID- 11962850
TI  - The national plan gives nurses the key to the cockpit and a licence to fly.

PMID- 11962851
TI  - Lights, camera ... traction.

PMID- 11962852
TI  - Seen & not heard.

PMID- 11962853
TI  - The parent trap.

PMID- 11962854
TI  - Care and treatment of haemangioma.

PMID- 11962855
TI  - Haemangioma: Hannah's story.

PMID- 11962856
TI  - School nurses and contraception.

PMID- 11962857
TI  - Labour gets tough on regulation.

PMID- 11962858
TI  - Nurse killer judge calls for tighter checks on recruits.

PMID- 11962859
TI  - Interpretation of wounds.

PMID- 11962860
TI  - A practical guide to treating asthma.

PMID- 11962861
TI  - Communication in the information age.

PMID- 11962862
TI  - Communicating with colleagues: documentation.

PMID- 11962863
TI  - New matron to stalk the wards.

PMID- 11962864
TI  - Paws for thought.

PMID- 11962865
TI  - Long-term care. Blow to elderly care, say nurses.

PMID- 11962866
TI  - Nurse smelling of drink on duty sacked unfairly.

PMID- 11962867
TI  - Covert medication. Hidden pills OK says UKCC.

PMID- 11962868
TI  - Scandal of nurses homes left to rot.

PMID- 11962869
TI  - Mental health nursing. Back-door route to generic nursing.

PMID- 11962870
TI  - Workplace violence. Judge cracks down as violence soars.

PMID- 11962871
TI  - Industrial action. Nurses threaten strike at flagship PFI hospital.

PMID- 11962872
TI  - Professional boundaries. Heads you do, tails you don't do day surgery.

PMID- 11962873
TI  - Osteoporosis. British women lagging behind in bone-disease awareness.

PMID- 11962874
TI  - Creutzfeldt-Jakob disease. A devastating diagnosis.

PMID- 11962876
TI  - The same old story.

PMID- 11962875
TI  - Is leadership in nursing more myth than substance?

PMID- 11962877
TI  - Private health needs public approval.

PMID- 11962879
TI  - It's hard to get back to the beginning.

PMID- 11962878
TI  - Doctors should be mindful of pain source.

PMID- 11962880
TI  - Nursing has moved on, but have you?

PMID- 11962881
TI  - Damaging and demoralising.

PMID- 11962882
TI  - Trust me, I'm a nurse.

PMID- 11962883
TI  - Feeling support.

PMID- 11962884
TI  - Calming influence or chemical cosh?

PMID- 11962885
TI  - The happy wanderer.

PMID- 11962888
TI  - School's back!

PMID- 11962886
TI  - Excellent plan in theory but it won't work without more, better paid nurses.

PMID- 11962889
TI  - Healthy hang-out for young East Enders.

PMID- 11962887
TI  - What steps should I take to report the abuse of a patient?

PMID- 11962890
TI  - Managing the risks posed by intravenous therapy.

PMID- 11962891
TI  - NHS national plan. Revamp swells jobs by 15,000.

PMID- 11962892
TI  - Forensic pathology: exhibits.

PMID- 11962893
TI  - Specialising in older people.

PMID- 11962894
TI  - Oxygen therapy--2.

PMID- 11962895
TI  - Communication and responsibility.

PMID- 11962896
TI  - Mental health nursing. Special hospitals must go, say MPs.

PMID- 11962897
TI  - Management. Bosses ridicule Virgin report on NHS bureaucracy.

PMID- 11962898
TI  - An extra pair of hands.

PMID- 11962899
TI  - Sterile instruments. 'Infection risk in GP surgeries'.

PMID- 11962900
TI  - NHS national plan. Educators' views ignored.

PMID- 11962901
TI  - Winter pressures. Switch patient to avoid fine, nurse told.

PMID- 11962902
TI  - Abortion. Pro-life protests feared.

PMID- 11962903
TI  - Crime. Nurse gets life for husband's murder.

PMID- 11962904
TI  - Drug error. Safety shake-up after baby death.

PMID- 11962905
TI  - Clear voice for Scottish nurses.

PMID- 11962906
TI  - Nutrition. Nurses get into beef over burger vans outside school gates.

PMID- 11962907
TI  - Cyclical vomiting syndrome. A disease they couldn't name: our battle with CVS.

PMID- 11962908
TI  - When she's not just off her food.

PMID- 11962909
TI  - Cleft lip and palate services. Facing up to an uncertain future.

PMID- 11962910
TI  - Midwifery. Postnatal care scores low marks with parents.

PMID- 11962911
TI  - Helping hand for the NHS.

PMID- 11962912
TI  - What are electronic records?

PMID- 11962913
TI  - Is information always good for patients?

PMID- 11962914
TI  - Keep an eye on the potato.

PMID- 11962915
TI  - Zen and the art of losing your self.

PMID- 11962916
TI  - Out of touch with role of consultants.

PMID- 11962917
TI  - Open your eyes to learn.

PMID- 11962918
TI  - Time for nursing to come into the garden.

PMID- 11962919
TI  - The gender agenda.

PMID- 11962920
TI  - Patient power.

PMID- 11962921
TI  - What's the UKCC waiting for? Until it acts, this nurse is fair game for tabloids.

PMID- 11962922
TI  - A rocky road back.

PMID- 11962923
TI  - Games without frontiers.

PMID- 11962924
TI  - Advancing dermatology nursing in the community.

PMID- 11962925
TI  - The pharmacology of acute pain.
AB  - Multimodal analgesia is the cornerstone of acute pain management. Paracetamol and
      NSAIDs provide background analgesia to which opioids and or adjuvant analgesics
      can be added, once the cause of pain is identified. Although simple analgesics
      have fixed-dose regimens, individual patient titration of opioids is essential.
      Dispelling opioid myths is fundamental to achieving this. Different routes of
      administration should not affect the level of analgesia achieved. Prompt
      recognition and treatment of side-effects helps to optimise pain management.

PMID- 11962926
TI  - Child death allegations. MPs slam UKCC probe 'scandal'.

PMID- 11962927
TI  - Pulse oximetry: benefits and limitations.

PMID- 11962928
TI  - Pulse oximetry--1.

PMID- 11962929
TI  - Communicating with colleagues.

PMID- 11962930
TI  - Police investigation. No evidence of nurse's guilt.

PMID- 11962931
TI  - Great Ormond Street. Parents seek reassurance.

PMID- 11962932
TI  - Social services. Hard-up council leaves elderly to linger in hospital.

PMID- 11962933
TI  - Let's talk about sex. Simply and plainly.

PMID- 11962934
TI  - Funding row. Section 28 nurse reported to UKCC.

PMID- 11962935
TI  - Children's nursing. Home is where the hospice is.

PMID- 11962943
TI  - Asthma nursing. Whole lotta puffin' going on.

PMID- 11962946
TI  - Don't fear the reaper.

PMID- 11962947
TI  - Forbidden love.

PMID- 11962948
TI  - Keep your distance.

PMID- 11962949
TI  - How should a practice nurse respond to a patient in pain who dislikes seeing the
      GP?.

PMID- 11962950
TI  - Asbestos. 'A cruel and nasty disease'.

PMID- 11962951
TI  - Resources for better practice. Uterovaginal prolapse: prevention and treatment.

PMID- 11962952
TI  - Monitoring fluid balance in acutely ill patients.

PMID- 11962953
TI  - Performance management. How to manage--Part. 6.

PMID- 11962954
TI  - Leadership award winner: communication for care. Interview by Jenine WIllis.

PMID- 11962955
TI  - Introduction to 12-lead electrocardiograms.

PMID- 11962956
TI  - Recording a 12-lead electrocardiogram--2.

PMID- 11962959
TI  - That will be the day....

PMID- 11962965
TI  - Reporting errors. Cheesed off with the blame culture.

PMID- 11962966
TI  - Campaign. Avoiding slips, trips, broken hips.

PMID- 11962969
TI  - Points system goes off track.

PMID- 11962968
TI  - Immunisation. School nurses burnt out by meningitis C campaign.

PMID- 11962970
TI  - Are nurses responsible for disseminating their work?

PMID- 11962972
TI  - Can pay, won't pay.

PMID- 11962971
TI  - Children with HIV. Ceausescu's children.

PMID- 11962975
TI  - We have a big problem with a little fat.

PMID- 11962976
TI  - No silk purse from this sow's ear.

PMID- 11962977
TI  - Clean up your act.

PMID- 11962978
TI  - Hand in hand.

PMID- 11962979
TI  - Dangerous liaisons?

PMID- 11962980
TI  - Multiple sclerosis: a fast-track service.

PMID- 11962982
TI  - Patient-controlled analgesia.
AB  - This overview has addressed some of the key principles relating to patient
      controlled analgesia. It is important to remember that PCA will continue to
      develop in the future and new techniques are being devised. PCA can provide an
      effective method of analgesia for many patients. However, it is not the only form
      of analgesia available, therefore a thorough assessment must be made before
      starting to use this analgesic technique.

PMID- 11962981
TI  - Group B streptococci and early onset neonatal infection.

PMID- 11962985
TI  - Communicating with colleagues.

PMID- 11962984
TI  - Loneliness and older people's health.

PMID- 11962986
TI  - Cardiac monitoring--2.

PMID- 11962988
TI  - Simply breathtaking.

PMID- 11962992
TI  - Whistleblowing. My message: if in doubt, speak out. Interview by David Payne.

PMID- 11962994
TI  - Workplace injuries. Early retirement: who's to blame?

PMID- 11962995
TI  - Infant development. Babies ae born communicators.

PMID- 11962996
TI  - Workplace violence. Call for police officer in every A&E.

PMID- 11962998
TI  - State hospital. Nurse loses claim over link to patient sex case.

PMID- 11962997
TI  - Sexual health. Anger at delay of national strategy.

PMID- 11962999
TI  - Does nursing research merely state the obvious?

PMID- 11963000
TI  - If only we could just say no.

PMID- 11963001
TI  - Sex is more complex than French verbs.

PMID- 11963002
TI  - Polio vaccine payback is still not enough.

PMID- 11963003
TI  - Genome project: the rich will inherit the earth.

PMID- 11963005
TI  - No sleep until September.

PMID- 11963004
TI  - Jobs for the boys and jobs for the girls.

PMID- 11963006
TI  - Men behaving madly.

PMID- 11963007
TI  - In your face.

PMID- 11963008
TI  - Surely nurses are as entitled to express their individuality as the next person?

PMID- 11963009
TI  - End of the road.

PMID- 11963010
TI  - Long-term care. No justice, no peace.

PMID- 11963011
TI  - Quality at a price.

PMID- 11963012
TI  - Nursing and forensic pathology.

PMID- 11963013
TI  - Combating phlebitis: a peripheral cannula grading scale.

PMID- 11963014
TI  - Beware the power to coerce.

PMID- 11963015
TI  - Uniforms. Nurses protest over dress code.

PMID- 11963016
TI  - In the melting pot.

PMID- 11963017
TI  - How do you feel?

PMID- 11963018
TI  - Oxygen therapy--1.

PMID- 11963019
TI  - Enhancing communication skills.

PMID- 11963020
TI  - Creutzfeldt-Jakob disease. Caring professions 'indifferent' to CJD.

PMID- 11963021
TI  - It is what you do, not the way that you do it.

PMID- 11963022
TI  - Accountability. Psychotic nurse went on to kill.

PMID- 11963023
TI  - Nurse education. Power surge for leading light.

PMID- 11963024
TI  - Midwifery. Bottle-feeding mothers feel neglected by midwives.

PMID- 11963031
TI  - Are ward leaders powerful advocates in a clinical setting?

PMID- 11963032
TI  - Why Leo is one of the lucky ones.

PMID- 11963036
TI  - Picking up the pieces of elderly care.

PMID- 11963037
TI  - Milburn's moment.

PMID- 11963038
TI  - Is work driving you to drink?

PMID- 11963039
TI  - Should I tell the DSS my client is cheating on benefit claims?

PMID- 11963040
TI  - Challenging violence.

PMID- 11963041
TI  - The nature of pain.
AB  - Pain is complex and difficult to define; Managing pain is challenging for all
      members of the interprofessional team; Untreated pain is harmful to the patient;
      Pain is a subjective and unique experience for the individual, which we, as
      health professionals, should not judge; Staff do not know best--listen to what
      the patient is telling you; Base your evaluation of pain upon a thorough clinical
      assessment and an evaluation of treatment/care. Use pain measurement tools to aid
      this process; Effective communication with patients is essential for effective
      pain management.

PMID- 11963043
TI  - G grade upgrade.

PMID- 11963044
TI  - Why clinical supervision is not so super in reality.

PMID- 11963045
TI  - Communicating with patients and carers.

PMID- 11963046
TI  - Congenital heart disease--1. Exploring normal anatomy and physiology.

PMID- 11963048
TI  - A quick print works wonders.

PMID- 11963052
TI  - Alternative medicine. Illness from an earlier life.

PMID- 11963051
TI  - Neonatal infection. Sad reality behind soap's storyline. Interview by Caroline
      Ryan.

PMID- 11963053
TI  - Eating disorders. Doctors fear that magazines get fat on thin images.

PMID- 11963054
TI  - A case for cannabis.

PMID- 11963055
TI  - Section 28. A law for bullies.

PMID- 11963056
TI  - Paediatric health care. Town calls for the heads of health officials.

PMID- 11963058
TI  - Kevin Cobb case. Improved whistleblowing at Cobb hospital.

PMID- 11963059
TI  - Is there a rational basis underlying alternative medicine?

PMID- 11963062
TI  - In a class of their own.

PMID- 11963063
TI  - Organ recital. Interview by Alison Whyte.

PMID- 11963064
TI  - Learning disabilities. No Rose without a thorn.

PMID- 11963065
TI  - Personal experience. I've got what you've got.

PMID- 11963066
TI  - Knowing the patient's point of view.

PMID- 11963067
TI  - Insight into what patients need.

PMID- 11963068
TI  - Pressure to be a role model.

PMID- 11963069
TI  - I don't want to cause distress.

PMID- 11963070
TI  - Kidney transplant for Asian people--does biology discriminate?

PMID- 11963072
TI  - Parents with learning disabilities need support.

PMID- 11963073
TI  - A leading light in coronary care. Interview by Jenine Willis.

PMID- 11963074
TI  - Cardiac monitoring.

PMID- 11963075
TI  - Cardiac monitoring--1.

PMID- 11963076
TI  - Forms and basic skills of communication.

PMID- 11963079
TI  - Home front.

PMID- 11963082
TI  - Screening is not worth the pain or the money.

PMID- 11963084
TI  - Not afraid to get her hands dirty. Interview by Robert Munro.

PMID- 11963085
TI  - A&E. We get a raw deal, claim drug users.

PMID- 11963086
TI  - Infection control. Survey reveals lack of data on hospital infections.

PMID- 11963087
TI  - RCN/HCA debate. Let us come in, HCAs tell RCN.

PMID- 11963088
TI  - Psychiatric nursing. The way you look freaks me out.

PMID- 11963089
TI  - Personality disorder. Government 'sets back civil rights by a thousand years'.

PMID- 11963090
TI  - Forensic nursing. Ashworth: will isolating the patient do any good?

PMID- 11963092
TI  - What is Zyban?

PMID- 11963091
TI  - Professional boundaries. It's time to bury the hatchet--but not in each other.

PMID- 11963093
TI  - Do community nurses and health visitors have a moral duty to help end smacking?

PMID- 11963094
TI  - Hanging out by the gene pool.

PMID- 11963095
TI  - Space to do their own thing.

PMID- 11963096
TI  - Half measures will not do.

PMID- 11963097
TI  - Families need more than a quick fix.

PMID- 11963098
TI  - Knowledge of maths is crucial.

PMID- 11963099
TI  - Miscalculation on maths aids.

PMID- 11963100
TI  - A natural way to deal with a miscarriage.

PMID- 11963101
TI  - Why I've turned into an old nark.

PMID- 11963102
TI  - Jointly and severally.

PMID- 11963103
TI  - Will hospices just slip quietly away?

PMID- 11963104
TI  - An emotive subject: nurses' feelings.

PMID- 11963105
TI  - Double standards threaten public trust in the nursing profession.

PMID- 11963106
TI  - Seriously lacking.

PMID- 11963107
TI  - Back to school.

PMID- 11963109
TI  - Nurse prescribing fails to deliver.

PMID- 11963108
TI  - What should I do about a colleague acting suspiciously?

PMID- 11963110
TI  - Why wear surgical face masks?

PMID- 11963111
TI  - Child deaths inquiry. Nurse insists 'I didn't kill the babies'.

PMID- 11963112
TI  - Paravertebral block analgesia.

PMID- 11963113
TI  - Pulse oximetry: a case study.

PMID- 11963114
TI  - Pulse oximetry--2.

PMID- 11963115
TI  - Communicating with patients.

PMID- 11963116
TI  - UKCC. Confusion over porn suspensions.

PMID- 11963117
TI  - Compensation. Legal win could double pay-outs.

PMID- 11963118
TI  - NHS confederation. Call to boost nurse skills.

PMID- 11963119
TI  - Health law. Mixed sex wards could breach human rights law.

PMID- 11963120
TI  - Wales. LHGs ignore 'anecdotal' nurse views.

PMID- 11963121
TI  - Laundry was the first to go, now it's clinical care.

PMID- 11963122
TI  - DNR orders. Nurses tell doctors not to resuscitate.

PMID- 11963123
TI  - Dementia. Still hungry in hospital and home.

PMID- 11963124
TI  - HIV nursing. Unit's first child is living proof of anti-HIV treatment.

PMID- 11963125
TI  - Recruitment and retention. More than just an image problem.

PMID- 11963127
TI  - Nursing history. Centre which aims to give the past a future.

PMID- 11963126
TI  - Mental health nursing. Staff shortages threaten mental health targets.

PMID- 11963128
TI  - Despair over nurse's death sentence.

PMID- 11963129
TI  - Chronic widespread pain. In serious pain or just bellyaching?

PMID- 11963130
TI  - Heart disease. Researchers give eggs a break.

PMID- 11963131
TI  - Learning disabilities. 'Vibrant' nurses in from the cold.

PMID- 11963132
TI  - Do hospital soaps give a false impression of nursing?

PMID- 11963133
TI  - The laughing genome.

PMID- 11963135
TI  - A funny job, but a bizarre view.

PMID- 11963134
TI  - Keeping up standards.

PMID- 11963136
TI  - Gynaecology is no job for a gentleman.

PMID- 11963137
TI  - Find the time to visit Earth.

PMID- 11963138
TI  - Police action may stifle the whistleblowers.

PMID- 11963139
TI  - WHO dares and wins.

PMID- 11963140
TI  - Don't believe the hype.

PMID- 11963141
TI  - If students are employees, let's pay them a wage; otherwise let them have loans.

PMID- 11963142
TI  - Natural miscarriage.

PMID- 11963143
TI  - Doing the rounds.

PMID- 11963144
TI  - Should I have given a dying patient a drink?

PMID- 11963145
TI  - The role of the nurse specialist in raising the profile of children's mental
      health.

PMID- 11963146
TI  - Epidural analgesia management.
AB  - Epidural analgesia can provide excellent pain relief for patients. Nurses must
      have a knowledge of its application and possible adverse effects so as to provide
      high-quality care. Epidural analgesia may be delivered as a continuous infusion
      or a bolus injection. Opioids and local anaesthetics are the main drugs used.
      Close monitoring of the patient is vital to detect any adverse effects.

PMID- 11963147
TI  - Death probe nurse stays on register.

PMID- 11963148
TI  - St John's wort and drugs: what nurses need to know.

PMID- 11963149
TI  - Assessed for success.

PMID- 11963150
TI  - Congenital heart disease--2.

PMID- 11963151
TI  - Overcoming difficulties in communicating with other professionals.

PMID- 11963152
TI  - Scotland. Soaring violence against nurses.

PMID- 11963153
TI  - AIDS charities. Section 28 case flops.

PMID- 11963154
TI  - Careers focus. A flexible friend.

PMID- 11963155
TI  - Infectious diseases. Priorities set without nurses' input.

PMID- 11963156
TI  - Leg ulcers. RCN guidelines cut healing time.

PMID- 11963157
TI  - Scottish top-security hospital. Safety overhaul after assault.

PMID- 11963159
TI  - Needlestick injuries. US nurse needles congress.

PMID- 11963158
TI  - Treat the whole woman not just her plumbing.

PMID- 11963160
TI  - Children with HIV. From the cradle to the grave.

PMID- 11963161
TI  - Drilling down for market viability. Providers prepare for the arrival of the
      'silent generation.'.

PMID- 11963162
TI  - The lingering insurance question. The cost and availability of liability coverage
      can sometimes trump even the best demographic profiles.

PMID- 11963163
TI  - Creating a virtual university. Technology helps facilitate the presentation of a
      diversified curriculum to a broad range of students at multiple locations.

PMID- 11963164
TI  - CMS changes Medicare enrollment form.

PMID- 11963165
TI  - Caregivers team up to manage pain.

PMID- 11963166
TI  - Getting ready for standardized transactions.

PMID- 11963167
TI  - [Pharmacogenomics of the immunosuppressive agents].

PMID- 11963168
TI  - [Clinical implication of cyclosporin for systemic autoimmune diseases: relevance
      to multidrug resistance].

PMID- 11963169
TI  - [Efficacy of in travenous cyclophosphamide therapy on rheumatic diseases].

PMID- 11963170
TI  - [Hyper IgM syndrome].

PMID- 11963171
TI  - [Agammaglobulinemia].

PMID- 11963172
TI  - [X-linked lymphoproliferative syndrome].

PMID- 11963173
TI  - [Wiskott-Aldrich syndrome; evaluation of WASP function in vitro using clinical
      samples].

PMID- 11963174
TI  - [Drug therapy on patients with systemic lupus erythematosus].

PMID- 11963175
TI  - [X-linked severe combined immunodeficiency].

PMID- 11963176
TI  - [Progress in study of autoantibodies in connective tissue diseases].

PMID- 11963177
TI  - [Updates in autoimmune bullous skin diseases].

PMID- 11963178
TI  - [Genetic analysis of allergic disorders with SNPs].

PMID- 11963179
TI  - [Reports by Research Committee on Intractable Vasculitides supported by Health
      Science Research Grants, the Ministry of Health, Labour and Welfare of Japan].

PMID- 11963180
TI  - [Genes responsible for rheumatic disease as a multifactorial disease: a genome
      approach from mouse to human].

PMID- 11963181
TI  - [Role of Fc receptor in the development of collagen-induced arthritis].

PMID- 11963182
TI  - [Immunological analysis and experimental immunotherapy for HTLV-I-infected T
      lymphoproliferative disease in a rat model].

PMID- 11963183
TI  - [Treatment of intractable diseases by a new bone marrow transplantation method].

PMID- 11963184
TI  - [Tetrameric MHC-peptide complex identifying CD8+ T cells specific to Epstein-Barr
      virus and human cytomegalovirus].

PMID- 11963185
TI  - [The role of hepatitis B and C virus-specific CTL in the control of viral
      replication].

PMID- 11963187
TI  - [Immunosuppression by gene transfection].

PMID- 11963186
TI  - [Host genetic polymorphisms in the pathogenesis of HIV-1 infection].

PMID- 11963188
TI  - [Guideline on the disease picture of hypertrophic anal papilla].

PMID- 11963189
TI  - [Primary sinu-nasal melanomas. Clinical aspects, therapy and follow-up].
AB  - BACKGROUND AND OBJECTIVE: Primary malignant melanoma of the nasal cavity and
      paranasal sinuses is a rare entity felt to have a poor prognosis. We examined the
      frequency and characteristics of this type of melanoma in a defined geographic
      region over a period of 16 years. PATIENTS/METHODS: Nine patients (eight men, one
      woman, mean age 62 years) with primary nasal and sinusoidal malignant melanoma
      were treated between 1985 and 2000 in the Department of Dermatology in
      cooperation with the Department of Otorhinolaryngology. All patients underwent
      surgery, eight with clinical complete tumor removal and one with only partial
      removal. All patients had radiotherapy after surgery. History, potential risk
      factors, clinical presentation, histological and immunohistochemical data and
      clinical course were documented. RESULTS: All patients died because of their
      tumor within the observation period (median survival: 30 months, range 7 to 75
      months). There were three different courses of the disease: (1) uncontrollable
      primary tumor (one patient, survival 11 months); (2) local recurrence with
      metastasis (five patients, median survival 40.2 months); (3) metastasis after a
      disease-free interval (three patients, median survival 19.3 months). CONCLUSIONS:
      Malignant melanoma of the nasal cavity and paranasal sinuses is a rare entity
      which is usually rapidly fatal. Effective treatment approaches are not available.

PMID- 11963190
TI  - [CD8-positive, CD30-negative cutaneous T-cell lymphoma simulating pyoderma
      gangrenosum].
AB  - Ulcerated primary cutaneous lymphomas are not rare, but the clinical
      manifestation as a pyoderma gangrenosum look-alike is extraordinary. CD8-positive
      lymphomas are rare, unclassifiable tumours with variable prognosis. We report on
      a 49-year-old patient with a large ulcerated primary cutaneous lymphoma on the
      left chest wall presenting as pyoderma gangrenosum. With immunohistochemical
      staining, most lymphocytes were shown to be CD8-positive. The CD30 antigen was
      not expressed. After radiotherapy with complete skin irradiation, the lymphoma
      regressed completely. The patient has been free of relapse for 28 months so far.

PMID- 11963191
TI  - [Squamous epithelial carcinoma as a complication of lupus vulgaris].
AB  - Lupus vulgaris represents a type of cutaneous tuberculosis that, if not correctly
      treated, presents a progressive chronic development whose long-term complications
      include cutaneous neoplasms. We report on a 55-year-old man presenting a 10-year
      old ulcerated and bleeding lupus vulgaris lesion on the left cheek containing a
      squamous cell carcinoma. Reviewing the literature, we search for possible causes
      of delay in diagnosis that even now allowed therapy only after discovery of the
      tumoral complication.

PMID- 11963192
TI  - [Scleredema adultorum in secondary hyperparathyroidism].
AB  - Scleredema adultorum, or Buschke's scleredema, belongs to the group of mucinoses.
      It is characterised by thickened and indurated skin. Histopathology shows
      thickened dermis with an infiltration of mucin between swollen collagen bundles.
      There are reports about many associations with scleredema adultorum, e.g., with
      diabetes mellitus and multiple myeloma. One case is known with associated primary
      hyperparathyroidism. For the first time we report a case of scleredema adultorum
      and secondary hyperparathyroidism, in a 46-year-old patient. Both forms of
      hyperparathyroidism have increased levels of parathormone. Therefore, these
      increased levels could have an influence on collagen metabolism.

PMID- 11963193
TI  - [Papulosquamous skin dermatoses on dark skin].

PMID- 11963194
TI  - [Modern wound management].

PMID- 11963195
TI  - [Cyproterone acetate].

PMID- 11963196
TI  - [Comment on O. Hoch et al.: "Thalidomide in treatment of cutaneous and systemic
      sarcoidosis"].

PMID- 11963197
TI  - [Oral anticholinergic therapy of focal hyperhidrosis with methanthelinium bromide
      (Vagantin). Initial data on effectiveness].

PMID- 11963198
TI  - [The German Dermatological Society moves its business office to Berlin].

PMID- 11963199
TI  - [The tick stings! Observations on a misnomer]].
AB  - Dermatology enjoys a unique distinction of visualizing its subject matter and
      should attain complete unity between a dermatologic term and the clinical concept
      therewith expressed. Clear and definite terminology seems indispensable.
      Unfortunately wrong designations sanctioned by daily use are incorporated in
      official nomenclature. How parasitology tells us that a tick stings and that a
      "tick bite" is a misnomer is detailed in this article.

PMID- 11963200
TI  - [Plant-induced toxic and allergic dermatitis (phytodermatitis)].
AB  - Herbal products are being used increasingly for medical or cosmetic purposes.
      Many cosmetics contain plant extracts for fragrance. Sensitizing plants in
      cosmetics are tea tree oil, arnica, chamomile, yarrow, citrus extracts, common
      ivy, aloe, lavender, peppermint, and others. However, the sensitizing potential
      of these plants varies. Most of the sensitizing substances are sesquiterpene
      lactones or terpenes. The present paper reviews the various forms of
      phytodermatitis, including irritant plant dermatitis, phototoxic and photo
      allergic dermatitis, allergic dermatitis, and airborne contact dermatitis.

PMID- 11963201
TI  - [Sports as a risk factor and therapeutic principle in dermatology].
AB  - Sporting activities may exert positive and negative health effects. This applies
      not only to the cardiovascular and musculoskeletal system, but also to skin.
      During sporting activities a person is exposed to environmental factors such as
      temperature, irradiation, and allergens. These factors may play a key role in the
      development of skin diseases. Mechanical trauma is caused by acute injury as well
      as chronic damage. Infectious skin diseases caused by viruses, bacteria or fungi
      can be transmitted by body contact or the use of communal showers or locker
      rooms. Intake of performance-enhancing substances may provoke skin changes such
      as striae distensae, androgenetic alopecia, hypertrichosis and acne. Preexisting
      skin diseases such as psoriasis, lichen planus, vitiligo, polymorphous light
      eruption, lupus erythematosus, porphyria, urticaria, and acne rosacea may be
      aggravated by sporting activities. On the other hand, physical exercise has a
      therapeutic potential which has hardly been exploited by dermatologists.
      Especially in chronic skin diseases positive effects have been observed.
      Therapeutic use of team sports has been shown to decrease suffering, depression,
      and emotional disturbances and increase life quality in patients with atopic
      eczema, psoriasis, and venous leg ulcers.

PMID- 11963202
TI  - [Role of glycoprotein IIb/IIIa inhibitors in the treatment of degenerated
      aortocoronary saphenous vein grafts].
AB  - Treatment of degenerated vein grafts is a large, growing portion of
      interventional procedures. Because the operative risk of repeat bypass surgery is
      substantially increased, percutaneous transluminal coronary angioplasty has been
      accepted as a less invasive treatment in symptomatic patients with significant
      stenoses of vein grafts. Stent placement has been established in the randomized
      SAVED trial as a safe and efficient treatment strategy of degenerated saphenous
      vein grafts, enhancing acute success, reducing the incidence of subsequent
      angiographic restenosis, and improving event-free survival. Despite coronary
      stents and new technological innovations like directional and transluminal
      extraction atherectomy distal embolization is still a frequent occurrence, with a
      reported incidence of 10-15% associated with an increased in-hospital mortality.
      Blockade of the platelet surface glycoprotein IIb/IIIa receptors has been
      convincingly demonstrated to reduce the ischemic complications of angioplasty in
      native coronary arteries. In degenerated vein grafts the efficacy of glycoprotein
      IIb/IIIa inhibitors in reducing distal embolization is uncertain. Major clinical
      events could not be reduced by glycoprotein IIb/IIIa antagonists administered
      periprocedurally. But prospective randomized trials are lacking. Protection
      devices could reduce the incidence of distal embolization during interventions in
      degenerated saphenous vein grafts. The relative role of these devices compared to
      pharmacologic interventions will require careful assessment in future clinical
      trials.

PMID- 11963203
TI  - [Radiofrequency catheter ablation of ventricular tachycardias].
AB  - Management of patients with ventricular tachycardia (VT) is often difficult. Drug
      therapy is often ineffective. Implantable cardioverter defibrillators (ICDs) can
      terminate VT episodes but do not prevent them. Radiofrequency (RF) catheter
      ablation can suppress arrhythmias in selected patients. However, the procedure is
      often challenging and success rates lower than for ablation of supraventricular
      tachycardias. The mapping and ablation approach depends on the VT mechanism.
      Monomorphic VT in patients without structural heart disease is referred to as
      idiopathic and has a focal origin. These VTs can be abolished by ablation in most
      of the patients. In VT due to reentry within an area of scar from an old
      myocardial infarction or cardiomyopathic process, critical parts of the circuit
      may be difficult to localize, rendering RF ablation challenging. In patients with
      monomorphic VT, prevention of VT recurrence can be achieved in 55% to 80% of
      patients. Multiple morphologies of VTs and circuits that are located deep in the
      endocardium are common problems that reduce efficacy. Furthermore, mapping to
      identify target regions for ablation can be more difficult if VT is rapid and not
      tolerated, or not inducible. Recently, multisite mapping of the arrhythmia
      substrate during sinus rhythm or multisite activation mapping of a few VT beats
      were shown to be effective for ablation of these "unmappable VTs". Bundle branch
      reentry tachycardia occur in patients with nonischemic cardiomyopathies, mostly
      valvular heart disease and can be successfully abolished with RF ablation of the
      right bundle. However, some of these patients may develop recurrences due to
      other types of VT. Recent technical developments have increased efficacy and
      simplified the approach of RF ablation of VT in patients with structural heart
      disease. However, long-term efficacy is not accurately predictable and
      implantation of an ICD is mandatory in most of the patients with severely
      depressed left ventricular function.

PMID- 11963204
TI  - [Mechanisms of initiation in atrial fibrillation].
AB  - Atrial fibrillation is the most relevant arrhythmia in daily clinical practice.
      The pathophysiology is determined by multiple independent reentrant wavelets in
      both atria. Repetitive triggers and an underlying substrate may favor the
      initiation and maintenance of atrial fibrillation. Mapping studies in patients
      with drug-refractory paroxysmal atrial fibrillation identified potentials from
      the ostia of pulmonary veins as a main source of triggers that initiate atrial
      fibrillation. In ongoing clinical trials, catheter ablation of pulmonary vein
      foci is used to eliminate atrial premature beats and thereby prevent the
      initiation of atrial fibrillation. The autonomic modulation of the heart rate and
      the occurrence of other supraventricular tachycardias that degenerate into atrial
      fibrillation are also considered as triggering mechanisms of atrial fibrillation.
      Since symptomatic bradycardia is associated with an increased incidence of atrial
      fibrillation, atrial pacing therapies for prevention of atrial fibrillation are
      another concept. Ongoing clinical trials evaluating the efficacy of pacing in
      patients with and without a primary pacemaker indication are currently under
      investigation. To date, data to which extent anatomical and electrophysiological
      characteristics of the atria influence the initiation and maintenance of atrial
      fibrillation are still missing. The myocardial adaptation to atrial fibrillation,
      the so-called "atrial remodeling", includes shortening of the atrial refractory
      period, slowing of atrial conduction, shortening of the atrial action potential,
      a progressive reduction of L-type calcium channel expression and microfibrosis of
      the myocardial tissue. New drug developments target atrial remodeling by
      modulating ion channel function and receptors of the angiotensin metabolism.

PMID- 11963205
TI  - [Quantitative analysis of the left main coronary artery by 3D echocardiography.
      Role, possibilities and limitations of noninvasive imaging of the left coronary
      artery].
AB  - The left main coronary artery was investigated in 30 patients using a
      transesophageal approach, and a 3D reconstruction of the 2D databases was
      performed. Two groups of patients were analyzed. First, patients with calcified
      aortic stenosis were investigated and the reconstructed data obtained were
      compared to the left ventricular angiogram of the left coronary artery. Second,
      the 2D databases of patients with non-calcified aortic valve and aortic anulus
      were reconstructed using the 3D technique. In group 1 the estimate in size of the
      left ventricular coronary artery was closely related to the diameter of the left
      coronary artery as obtained by the coronary angiogram (mean difference 0.08 mm,
      interval of confidence at 95%, -0.48 and +0.32 mm). In both groups a substantial
      increase in imaging of the left coronary artery was obtained compared to the
      standard 2D echocardiographic view (% in group 1, and % in group 2,
      respectively). Independent of the 3D reconstruction of the left coronary artery
      in the any-plane mode, an orthogonal imaging of the artery could be obtained in
      only 15% of patients in group 1 but in 40% of patients in group 2. We conclude
      that 3D reconstruction of the left coronary artery (LAD) is superior to 2D
      echocardiography in echo-imaging of the proximal part of the LAD and correlates
      strongly to the diameters measured in the left coronary angiogram. In patients
      with major calcification of the aortic anulus and/or a calcified native aortic
      valve this approach is associated with multiple artifacts in imaging. The rapid
      technical evolution in this technique including improvement in computer
      technology and appropriate software may ensure a further important role of 3D
      echo imaging in noninvasive visualization of the normal and diseased left main
      coronary artery.

PMID- 11963206
TI  - [Pullback atherectomy. An alternative procedure in the treatment of coronary
      stenosis and in-stent restenosis].
AB  - Optimized directional coronary atherectomy (DCA) has shown significantly superior
      acute and long-term results compared to conventional balloon angioplasty (BA).
      Nevertheless DCA has remained a niche application due to specific procedural
      aspects. The pullback atherectomy catheter (PAC), developed to retrieve
      atheromatous plaque material, is an alternative debulking device. We report on
      clinical and angiographic experience in 55 consecutive patients, in whom de novo
      lesions (35 pts) as well as instent restenoses (17 pts) were treated. The minimal
      luminal diameter (MLD, mm) rose after PAC and additional BA from 1.06 +/- 0.53 to
      2.68 +/- 0.48 and from 1.10 +/- 0.48 to 2.55 +/- 0.49 mm, respectively. A
      stenosis reduction from 69 +/- 13 to 19 +/- 16 and from 64 +/- 15 to 16 +/- 10%,
      resp., could be documented. After 3-6 months a complete angiographic follow-up
      showed MLD values of 2.01 +/- 0.69 and 1.88 +/- 0.61 mm. Nine of 35 (26%) vs. 5
      of 17 (29%) pts developed significant restenosis at the treated site (diameter
      stenoses > 50%). Stent implantation was necessary to achieve an optimal acute
      angiographic result or due to dissection in 17 vs. 5 pts. Major cardiac events
      did not occur; however, two restenosed coilstents were removed by PAC. With the
      pullback atherectomy catheter, a safe and effective alternative device is
      available for the treatment of coronary lesions and also of in-stent restenosis.
      Promising short and acceptable long-term results are comparable to those of other
      debulking procedures.

PMID- 11963207
TI  - [Long-term follow-up of patients with acute myocardial infarction treated with
      primary angioplasty or thrombolysis. Results of the MITRA trial].
AB  - Long-term follow-up after treatment with primary angioplasty compared to
      treatment with thrombolysis in patients with acute myocardial infarction (AMI)
      remains still to be determined. We therefore analyzed the data of the "Maximal
      Individual Therapy" in Acute Myocardial Infarction (MITRA-1) Registry. Follow-up
      data for a median of 17 months after discharge were available in 2090 out of 2195
      (95%) AMI patients treated with thrombolysis, as well as 293 out of 312 patients
      (94%) treated with primary angioplasty. There were only small differences in
      patient characteristics between the two treatment groups. Compared to patients
      treated with thrombolysis, those treated with primary angioplasty had a higher
      prevalence of prior myocardial infarction (16.4% versus 12.2%, p = 0.04), longer
      prehospital delay: 10 minutes (130 minutes versus 120 minutes, p = 0.002), and a
      longer door-to-treatment time: 45 minutes (p < 0.001). Primary angioplasty
      patients were more likely to be treated with beta-blockers (primary angioplasty
      79.8% versus thrombolysis 66.2%, p < 0.001) or statins (24.5% versus 16.5%, p <
      0.001). There was no difference between the treatment groups for total mortality
      (p = 0.90) nor for the combined endpoint of death or re-infarction (p = 0.85).
      However, the combined endpoint of death, re-infarction or percutaneous coronary
      intervention or coronary bypass surgery was significantly lower in the primary
      angioplasty group (primary angioplasty 25.6% versus thrombolysis 32.3%,
      univariate odds ratio 0.72, 95% CI: 0.55-0.95, p = 0.02). This result was
      confirmed by multivariate analysis after adjusting for confounding parameters
      (multivariate odds ratio: 0.62, 95% CI: 0.42-0.91). The beneficial effect of
      primary angioplasty compared to thrombolysis achieved during the hospital stay
      after an AMI is maintained during a 17 month follow-up. AMI patients treated with
      thrombolysis were more likely to be treated with either percutaneous coronary
      intervention or coronary bypass surgery after discharge.

PMID- 11963208
TI  - [Mobilization and retrieval of an entrapped guidewire in the righ coronary
      artery].
AB  - The elective PTCA of a highly stenotic right coronary artery was complicated by
      intracoronary entrapment of the guidewire. After transfer to a hospital with a
      stand-by cardiosurgical team, the interventional mobilization and withdrawal of
      the wire was performed. Initially the attempt to position a balloon-catheter
      through the entrapped guidewire failed due to a localized radiolucent piece of
      material attached to the tip of the wire. After introduction of an additional
      guidewire and consecutive dilation of the stenosis, gradual mobilization and
      removal of the wire was successful. During this maneuver the distal part of the
      guidewire ruptured and was caught in a side branch of the right femoral artery,
      where it could finally be retrieved, using a conventional retrieving device in a
      crossover technique. Intracoronary entrapment is a rare but potentially dangerous
      complication during coronary interventions, every cardiologist should be aware
      of, especially when treating tortuous vessels.

PMID- 11963210
TI  - Dissimilar atrial rhythms: coexistence of reentrant atrial tachycardia,
      atrioventricular nodal reentrant tachycardia and interatrial conduction block.
AB  - We report a patient in whom mapping of the right atrium with multipolar catheters
      and electroanatomic mapping revealed the presence of three dissimilar rhythms: a
      reentrant atrial tachycardia in the antero-lateral wall of the right atrium and
      an atrioventricular nodal reentrant tachycardia (AVNRT) isolated from each other
      and a conduction disturbance at the interatrial septum resulting in a rate
      related interatrial block and a slow left atrial rhythm. The AVNRT was stopped
      with intravenous adenosine (6 mg) and induced repeatedly by atrial extrastimuli
      associated with a critical atrioventricular delay and dual atrioventricular nodal
      pathways. Electroanatomic mapping disclosed extensive fibrosis isolating viable
      myocardium of the antero-lateral wall from the rest of the right atrium. The
      viable myocardium in the antero-lateral wall was activated by a reentrant rhythm
      circulating around an islet of fibrosis located in the middle of the viable
      tissue. The AVNRT was ablated by a standard approach and the reentrant atrial
      tachycardia by producing a linear lesion bridging the central islet of fibrosis
      with the anterior tricuspid annulus. This case highlights the complicated nature
      of some dissimilar atrial rhythms and the power of electroanatomic mapping tools
      to reveal the exact mechanism and guide radiofrequency ablation.

PMID- 11963209
TI  - [Evaluation of infrequent episodes of palpitations with a patient-activated hand
      held electrocardiograph].
AB  - The disadvantage of most devices presently available for cardiac rhythm event
      monitoring is that they require either permanently attached electrodes or the
      subcutaneous implantation of the device. The aim of the study was to evaluate the
      feasibility and diagnostic yield of a hand-held, portable electrocardiograph for
      the evaluation of infrequent episodes of palpitations. In contrast to other
      devices, this electrocardiograph records and stores the electrocardiograms with
      integral electrodes, which makes long-term attached electrodes not unnecessary.
      METHODS: The study included 55 consecutive patients with palpitations less than
      once a week. The patients received the electrocardiograph Miniscope MS-3 with
      integral tripod electrodes (Schiller AG, Switzerland) to record a one-channel
      electrocardiogram during a recurrent episode. The frequency of device activation
      and the atrial rhythm during an episode was assessed. RESULTS: Forty-one (75%)
      patients had at least one episode within 38 +/- 22 days. The first episode
      occurred within the first week in 18 cases, during the 2nd in 9, during the 3rd
      in 9, during the 4th in 2 patients, and in 3 patients between the 4th and 12th
      week. All episodes could be properly analyzed: Twenty-three patients had sinus
      rhythm, 7 paroxysmal atrial fibrillation, 7 paroxysmal atrial flutter, and 4 an
      AV node reentry tachycardia. Eleven of the 23 patients with sinus rhythm
      additionally had premature atrial or ventricular contractions. Mean heart rate
      was 111 +/- 45 bpm. A second episode was recorded in 22 and a third episode in 12
      patients. All patients had during the subsequent episode the same cardiac rhythm
      as during their first episode. CONCLUSIONS: Patients evaluated for their
      infrequent palpitations had during event monitoring a recurrent episode in 75%
      that occurred in 88% within the first 4 weeks. All patients were able to activate
      the electrocardiograph and could store an electrocardiogram with the integral
      electrodes. Patient-activated event monitoring reliably identified patients with
      an atrial arrhythmia who need further invasive evaluation and treatment, and
      ruled out patients with sinus rhythm and premature contractions.

PMID- 11963211
TI  - [Selective increase of ventricular pacing threshold with complete exit block
      following DC cardioversion in a patient with a dual chamber pacemaker].
AB  - We report the case of a 78-year old patient with a dual chamber pacemaker, who
      was admitted for cardioversion of atrial tachycardia. Transthoracic DC shock of
      160 J was followed by transient loss of ventricular capture with complete exit
      block and severe nodal bradycardia. Subsequent analysis of stimulation thresholds
      revealed a marked rise in the ventricular threshold only, whereas atrial
      threshold was unchanged. The selective dysfunction of ventricular capture is most
      likely caused by current-induced tissue damage at the electrode-endomyocardial
      interface by preferential shunting of high electrical energy into the ventricular
      lead as compared to the atrial lead. High output pacing prior to elective DC
      cardioversion is recommended to ensure consistent capture, particularly in
      pacemaker-dependent patients, and careful evaluation of pacemaker function after
      shock delivery should performed.

PMID- 11963212
TI  - [Sinus node dysfunction with intermittent sinus arrest and AV-nodal escape rhythm
      as initial manifestation of pheochromocytoma].
AB  - A 25-year-old male student complained about episodic palpitations, dizziness,
      nausea and headache 5 years prior to presentation. No otorhinolaryngic,
      neurologic or gastrointestinal causes were identified. Several ECG recordings
      revealed sinus node dysfunction with intermittent sinus arrest and AV-nodal
      escape rhythm. The patient was given a permanent DDD-pacemaker. Six months later,
      the clinical symptoms were unchanged. During an attack, physical examination
      revealed paleness, diffuse sweating and an arterial blood pressure of 250/130
      mmHg, which decreased to 120/80 mmHg within a few minutes. Abdominal ultrasound
      and abdominal computed tomographic scan demonstrated the presence of a large (6.4
      x 5.5 cm) left-sided adrenal mass. Two 24-h-urinary collections demonstrated
      elevated noradrenaline (mean 315 micrograms/24 h, normal < 80 micrograms/24 h)
      and adrenaline (mean 268 micrograms/24 h, normal < 20 mg/24 h) levels. Blood
      samples, which were drawn during excessive blood pressure rise, revealed
      elevation of plasma catecholamines (6.793 pg/ml for adrenaline (normal 50-150
      pg/ml) and 10.424 pg/ml for noradrenaline (normal 200-500 pg/ml), so that the
      diagnosis of pheochromocytoma was considered established. The tumor was
      successfully removed during laparascopic surgery. After surgery, the patient
      remained well and normotensive. Three months later, several long-term ECG
      recordings showed sinus arrhythmia with no evidence of sinus arrest or AV-nodal
      escape rhythm, so that the DDD pacemaker was turned off. This case underlines
      that sinus node dysfunction with intermittent sinus arrest and AV-nodal escape
      rhythm is a potential early manifestation of a pheochromocytoma. These changes
      seem to disappear after successful removal of the tumor.

PMID- 11963213
TI  - [Position report. Nuclear cardiology diagnosis. Update].

PMID- 11963214
TI  - ["Remembrance, speak..."].

PMID- 11963215
TI  - [From dermatology into cosmetics. Chance or risk?].

PMID- 11963216
TI  - [Dermatology in telemedicine. Possibilities and limits].
AB  - Telemedicine including teledermatology is the application of telecommunication
      technology for the purpose of diagnostics, planning and guiding of therapy and
      education. With the possibility to gain fast access to specialty knowledge,
      telemedicine makes it possible to deliver health care to patients at distant
      sites. By participating in telemedical consultations, patients receive accurate
      diagnosis in a rapid manner and save travel costs and time. Due to recent
      advances in computing and telecommunications technology, telemedicine will assume
      a more and more important role in future health care delivery. Telemedicine is
      utilized by almost all medical specialties but to varying degrees. Dermatology as
      a visually based specialty is predestined to use the various capabilities of
      telemedicine. The main applications so far include teledermatohistology and
      clinical teledermatology. The objective of this paper is to present the current
      status of teledermatology as part of telemedicine with a look toward future
      applications.

PMID- 11963217
TI  - [Acne inversa (stage 2)].

PMID- 11963218
TI  - [How large is the loss of effectiveness of a treatment procedure between "theory"
      and "practice"? Evaluating health economics basic data within the scope of a
      trial model of ambulatory synchronous balenophototherapy of atopic eczema].
AB  - BACKGROUND AND OBJECTIVE: Before introducing new treatment modalities, efficacy
      has to be proven in clinical trials. Furthermore, it is of special interest to
      what extent results of clinical trials can be transferred to daily routine.
      PATIENTS/METHODS: In the framework of a trial on out-patient synchronous
      balneophototherapy, a possible loss in treatment efficacy from "clinical trial"
      to "daily routine" was examined. Therefore all patients without protocol
      deviations (representing treatment success available in a "clinical trial") and
      all patients with at least one treatment session regardless of protocol
      deviations (model for "daily routine") were analyzed. RESULTS: 257 "daily
      routine" and 1281 "clinical trial" patients with atopic dermatitis were analyzed.
      Relative SCORAD-improvements provided a clear loss in treatment efficacy in the
      "daily routine" group of 14.2%: 55% of patients received less than the planned 3
      treatments per week and 48% left the study early because of noncompliance, good
      improvement, lack of time or lack of efficacy. CONCLUSIONS: For the first time a
      loss of efficacy of a treatment modality between "theory" and "practice" can be
      demonstrated in a representative number of patients suffering from atopic
      dermatitis. For the optimal use of rare financial resources, the comparison of
      different treatment modalities under "daily routine" conditions is also necessary
      in future.

PMID- 11963219
TI  - [Lupus erythematosus and sarcoidosis--coexistence or association?].
AB  - There are not many reports on simultaneous occurrence of the two rare multiorgan
      disorders lupus erythematosus and sarcoidosis. Since etiopathogenesis in both
      diseases is not yet fully defined, speculations concerning common immunological
      pathomechanisms as well as discussions about chance coexistence versus real
      association remain unsolved. As exemplified by our two patients, diagnostic
      problems may arise from the broad spectrum of cutaneous manifestations in both
      diseases as well as the similarity of extracutaneous symptomatology.

PMID- 11963220
TI  - [Recurrent palmoplantar hidradenitis in childhood].
AB  - We describe five cases of recurrent palmoplantar hidradenitis in children. The
      pathogenesis of this highly characteristic disease presenting with painful
      erythematous papules and nodules involving palms of the hands, soles of the feet,
      or both is not clear at the moment. One possible mechanism is a temporal
      relationship between exposure to dampness and cold, which also applied in four of
      these children. The self-limited disease tends to reappear. After thoroughly
      informing the children and their parents on avoiding provoking factors, all
      children experienced freedom from the disease during a 12-month follow-up.

PMID- 11963221
TI  - [Multiple miliary osteomas of the face].
AB  - Osteoma cutis is a single or multiple ectope calcification with development of
      bony structures in the skin. We distinguish between primary and secondary
      ossification. Multiple miliary osteoma in the face has mostly been described
      secondary to preexisting acne vulgaris. We present a 62-year-old woman who
      developed multiple miliary osteoma in the face together with repeated doses of
      estrogen and discuss pathogenesis and therapeutic possibilities.

PMID- 11963222
TI  - [Degos atrophic malignant papulosis. Not always malignant!].
AB  - A patient developed malignant atrophic papulosis with only cutaneous
      manifestation. Repeated coloscopy uncovered no malignant papules in the colon.
      Referring to the literature, the value of permanent anticoagulant therapy is
      discussed. In contrast to the term "malignant" atrophic papulosis, there also
      seems to be a variant with a benign clinical course.

PMID- 11963223
TI  - [Radiation-induced cutaneous hamartoma in a patient with Cowden syndrome.
      Clinical evidence for heterozygosity].
AB  - A 56-year-old woman had typical features of Cowden syndrome in the form of
      hamartomas involving the skin, lips, and oral mucosa. At the age of 48, a
      mastectomy was performed for adenocarcinoma with a regional metastasis, and X-ray
      treatment was applied to the left axilla. Subsequently the patient developed
      approximately 30 skin-colored nodules surrounding the irradiated axillary region
      within several months. Histopathological examination of one of these lesions
      showed characteristic features of sclerotic fibroma. The multiple radiation
      induced fibrous hamartomas observed may be best explained by multiple events of
      loss of heterozygosity (LOH), because molecular studies in other patients with
      Cowden syndrome have shown that both benign and malignant tumors originate from
      LOH. The X-ray treatment would have induced LOH in many cells, giving rise to
      either homo- or hemizygosity for the Cowden mutation.

PMID- 11963224
TI  - [Inhibin B as a marker of spermatogenesis. A new dimension in andrology].
AB  - In 1932, McCullagh postulated the existence of a specific hormone of the testis,
      regulating FSH secretion. He named this hormone inhibin. As we know today,
      several proteins of the inhibin family are produced in the Sertoli cells. The
      major product is inhibin B, consisting of a alpha- and a beta-subunit. It is also
      present in spermatogonia, spermatocytes and early spermatids. The serum levels of
      inhibin B increase in puberty. In the adult man they are correlated positively to
      sperm count and testis volume, but negatively to FSH levels. These correlations
      exist also in OAT syndrome independent of the cause of spermatogenic failure. In
      azoospermia high serum levels of inhibin B predict the existence of spermatozoa
      in the testis. This improves the prediction of the success of a TESE. It may be
      that the determination of inhibin B is superior to that of FSH.

PMID- 11963225
TI  - [Bullae, erosions and scars in the face of 2 girls with idiopathic arthritis.
      Naproxen-induced pseudoporphyria].

PMID- 11963226
TI  - [Tumor-associated genetic dermatoses].

PMID- 11963228
TI  - ["The Aging Man" Meeting. 12 May 2001 in Leipzig].

PMID- 11963227
TI  - [Maximum doses of local anesthetics. Changes due to addition of adrenaline?].

PMID- 11963230
TI  - [The acutely ill child--a challenge for radiodiagnosis].

PMID- 11963231
TI  - [Imaging techniques and examination protocols in the pediatric emergency].
AB  - Paediatric emergencies demand a quick and efficient radiological investigation
      with special attention to specific adjustments related to patient age and
      radiation protection. Imaging modalities are improving rapidly and enable to
      diagnose childhood diseases and injuries more quickly, accurately and safely.
      This article provides an overview of imaging techniques adjusted to the age of
      the child and an overview of imaging strategies of common paediatric emergencies.
      Optimising the imaging parameters (digital radiography, different screen-film
      systems, exposure specifications) allows for substantial reduction of radiation
      dose. Spiral- and multislice-CT reduce scan time and enable a considerable
      reduction of radiation exposure if scanning parameters (pitch setting, tube
      current) are properly adjusted. MRI is still mainly used for neurological or
      spinal emergencies despite the advent of fast imaging sequences. The
      radiologist's task is to select an appropriate imaging strategy according to
      expected differential diagnosis and to adjust the imaging techniques to the
      individual patient.

PMID- 11963233
TI  - [Acute abdomen in the child].
AB  - The acute abdomen in childhood demands early diagnosis for the sake of
      appropriate and early therapy. A high number of differential diagnosis in the
      assessment of acute abdominal pain and problems, as well as different causes of
      diseases in different age of the children, make a partition with respect to the
      age of the children considerable. A partition in diseases, which are leading to
      acute abdominal pain in neonates, in toddlers and small infants and in
      schoolchildren makes sense. In older schoolchildren and adolescents also diseases
      of the grown up generation are possible as a cause of acute abdominal pain. The
      lack of compliance (cooperation and communication) in small children obstructs
      clinical and radiological assessment and elucidates the necessity of knowledge of
      causes of acute abdominal pain as much as possible. A lot of patience and
      experience are mandatory in the evaluation of small children and therefore make a
      dedicated, trained and experienced stuff necessary. A dedicated paediatric
      radiologist will find a safe and proper technique, and in cooperation with the
      referring clinician the necessary decision for therapy will be made.

PMID- 11963232
TI  - [Acute, atraumatic changes of the lower respiratory tract in the child in
      thoracic roentgen imaging. Recognition and appreciation of radiological changes].
AB  - The diagnosis of acute, non-traumatic diseases of the lower respiratory tract
      requires exact knowledge of the specific anatomy, physiology and pathology of the
      pediatric chest. The absolutely and relatively smaller airways, as compared with
      those of adults, and the undeveloped collateral ventilation result in
      radiological appearances that are unique in children. Viral pneumonia is
      predominant only in small children up to an age of 2 years. With increasing age,
      there is a higher incidence of bacterial pneumonia. The differentiation of viral
      and bacterial etiology of a pneumonia is not possible on the basis of chest
      radiographs. In acute pediatric imaging, possible aspiration of foreign bodies
      has to be considered. Since most foreign bodies cannot be detected
      radiographically, indirect features such as hyperinflation or mediastinal shifts
      have to be evaluated. Primary lung tumors are rare in children. More common are
      metastases with known primary tumors. Neuroblastoma or lymphomas may mimic
      intrapulmonary pathologies.

PMID- 11963234
TI  - [Acute urogenital status].
AB  - The symptoms of a child indicating a urogenital emergency case are often
      unspecific. Clinical differentiation from a gastrointestinal disease may be
      impossible since typical clinical manifestations include vomiting, fever and
      acute onset of abdominal pain, sometimes with the symptoms of a colic. Efficient
      diagnostic work up is imperative with regard to these patients since a quick
      establishment of the correct diagnosis allows timely treatment which in turn may
      avoid irreversible damage. Clinical evaluation of externally visible changes of
      the genitals like reddening and swelling of the scrotum helps to limit the
      differential diagnosis to a certain extent. Congenital urogenital diseases should
      be diagnosed or assumed by means of routine sonography during pregnancy in order
      to avoid typical complications of a delayed diagnosis after birth. This article
      focuses on the description and discussion of an effective use of radiologic
      techniques in some of the common urogenital emergency cases.

PMID- 11963235
TI  - [Diagnostic imaging in acute neurological status in childhood].
AB  - The diagnostic imaging of children with acute, non-traumatic, neurologic symptoms
      enables a fast and non-invasive localization and diagnosis. A spectrum of typical
      disorders will be described dependent on the location of neurologic symptoms
      (central, spinal, or peripheral nervous system). Different non-invasive imaging
      modalities e.g. US with colour-coded doppler, CT, MRI are utilized dependent on
      age of the patient and neurologic symptoms. The purpose of this article is to
      describe the spectrum of diagnostic imaging for each of these common disorders.

PMID- 11963236
TI  - [The limping child. Differential radiologic diagnosis of acute gait disorder in
      childhood and adolescence].
AB  - Limping is a common and often challenging problem in children and adolescents. A
      limp is defined as asymetric deviation from a normal gait pattern. A systematic
      approach is necessary to determine the cause of the limp, so the radiologist
      should combine a thorough history, clinical information and pertinent radiologic
      testing. The possible differential diagnosis is extensive and includes many
      pathologies of the lower extremity and spine like trauma, infection, neoplasia,
      furthermore inflammatory, developmental and congenital disorders. In cases with
      knee or tight pain, an underlying hip condition should be considered. The childs
      age can narrow the possible differential diagnoses, because certain entities are
      age-related. Despite this wide bandwidth of entities, potential catastrophic
      causes like septic arthritis and malignant disease should be excluded first.
      Plain radiographs are often diagnostic. The choice of further imaging modalities
      like ultrasonography, magnetic resonance imaging, computed tomography and bone
      scan should be guided by the history and clinical findings.

PMID- 11963237
TI  - [Trauma radiology in the child].
AB  - The aim of this review article is to familiarize the reader with the specific
      paediatric conditions in trauma radiology. The article briefly describes the
      major pathophysiologic differences in childhood and the consecutive altered
      injury pattern. The standard radiological imaging protocol for various involved
      body regions and different trauma settings/varying queries is described, with
      suggestion for standardised diagnostic flow-charts in some typical settings.
      Special regard is given to radiation protection and the potential of newer
      imaging modalities such as ultrasound, multi-detector- and spiral CT as well as
      MRI in paediatric trauma patients. As such the paper hopefully provides some
      basic guidelines for general radiologists in peripheral hospitals who less often
      have to deal with paediatric queries.

PMID- 11963238
TI  - [Nontraumatic injury (battered child)].
AB  - The recognition of a battered child represents a challenge for all groups of
      adults dealing with children. Radiology plays a special role in this setting. By
      detection typical injuries, imaging is able to confirm the suspicion of a
      battered child. Recognition of those injuries on films, taken for other reasons,
      gives the caretaker an important hint, thus maybe preventing a fatal outcome for
      the child. One of the most important injury types is represented by the so called
      "shaken baby syndrome". The infant is held by the thorax and shaken. Thus causing
      a repetitive acceleration-deceleration trauma, which leads to the typical
      paravertebral rib fractures, intracranial bleeding and eye injuries. After
      shaking the child is thrown away, with subsequent injuries. The aim of this
      article is the presentation of an overview regarding the radiology of the
      battered child. Typical examples will be shown.

PMID- 11963239
TI  - [Rare acute disease pictures of the upper respiratory tract in children].
AB  - The radiologist should recognize dangerous uncommon conditions such as
      epiglottitis and membranous croup by their pattern on conventional images.
      Subglottic narrowing, as from croup, is recognizable on lateral images by loss of
      the superior interface of trachea and vocal cords. A lateral image is important
      when an upper esophageal foreign body is seen on a frontal view.

PMID- 11963240
TI  - [Dynamic contrast-enhanced MRI for evaluating bone marrow microcirculation in
      malignant hematological diseases before and after thalidomide therapy].
AB  - PURPOSE: The aim of the study was to measure microcirculation parameters by
      dynamic contrast-enhanced MRI (d-MRI) and to evaluate the anti-angiogentic
      effects during treatment with thalidomide in different hematologic malignancies.
      METHODS: In 20 healthy normal persons, 20 patients with myelodysplastic syndromes
      (MDS), 10 patients with multiple myeloma (MM) and 10 with myelofibrosis (MF) a
      fast gradient echo sequence (Turbo fast low angle shot 2D) with a pump controlled
      bolus infusion of gadolinium-DTPA was performed before and in 18 of these after
      beginning (average of 4.3 months) of a thalidomide therapy. Two pharmacokinetic
      parameters--the amplitude and exchange-rate-constant--were calculated and a
      statistical comparison of these values between healthy persons and patients as
      well as a correlation with the clinical course was executed. RESULTS: Compared
      with the normal controls the patients showed a higher amplitude (normal persons
      14.4 +/- 5.2, MDS 24.8 +/- 8.1, MF 35.9 +/- 4.3, MM 23.4 +/- 3.6) and exchange
      rate-constant (normal persons 0.124 +/- 0.042, MDS 0.136 +/- 0.036, MF 0.144 +/-
      0.068, MM 0.131 +/- 0.034). In the d-MRI-follow-up examinations a significant (p
      < 0.005) reduction of the amplitude and exchange rate constant values was evident
      in 14 of 18 patients undergoing a thalidomide therapy. Clinically all of these
      patients showed a therapy responding with complete or partial diseases remission.
      CONCLUSIONS: In patients with hematologic malignancies significantly higher d-MRI
      microcirculation parameters of the lumbar spine can be demonstrated than in
      normal persons. During anti-angiogenetic treatment with thalidomide a decrease of
      these values was observed in case of a responding to therapy.

PMID- 11963241
TI  - [Routine after-care 16 years after left adrenalectomy for adrenal cortex
      carcinoma. Late pulmonary metastasis of resected adrenal cortex carcinoma].

PMID- 11963242
TI  - [Duplex ultrasound of arteries and veins. II: Retroperitoneal blood vessels,
      pelvic and leg arteries, veins].

PMID- 11963243
TI  - [Quality assurance with teleradiology].
AB  - Teleradiology offers many applications for quality assurance in medicine. The
      spectrum reaches from electronic consultations in emergency or special cases and
      double reading--along with new models of cooperative work and medical networks-
      to technical quality assurance and integration into interinstitutional and
      patient controlled health records. Regional teleradiology networks based on
      server concepts can fulfill the developing technical and organisational
      requirements. The increasing mobility arising from smaller radiological equipment
      and improved accessibility to experts with minimized visualisation and reporting
      systems will change the radiological world of tomorrow, especially in combination
      with the usage of knowledge based systems in reference data bases and computer
      assisted diagnosis (CAD). Teleradiology by itself must be liable to quality
      assurance measurements to prevent unnecessary radiation exposure or danger to the
      doctor patient relation.

PMID- 11963244
TI  - [New international networks in radiology graduate and continuing education:
      www.eurorad.org--a EAR Project for online publication of radiological data].
AB  - Eurorad (www.eurorad.org) is a joint project of EAR and has support of 27
      national and 8 subspeciality radiology societies. Eurorad is the first
      noncommercial radiological publication that is exclusively based on the internet
      as a communication line with all steps of submission, reviewing and publication
      being performed online. Eurorad wants to build up a huge and exhaustive case file
      of diagnostic and interventional radiology. Like all scientific publications,
      Eurorad bases on an editor in chief and 13 section editors who are responsible
      for organizing each section of Eurorad. Each section has a number of peer
      reviewer with an overall total of more than 100. For submission and publication,
      all cases are structured in the same manner with case report, method and
      discussion. For the time being, Eurorad hosts 779 cases, of whom 346 are free
      available on the net. The actual rejection rate is 4.5%, other cases are under
      review.

PMID- 11963245
TI  - [The future of teleradiology: results of Teleradiology Expert Meeting of the
      Health Network Congress 2001].
AB  - Legal prerequisites have substantial influence on the development of
      teleradiology. At an expert meeting (Mannheim, 8.6.2001) a proposal for a
      teleradiology article in the new German x-ray ordinance has been set up. An
      exception of the demand for a doctor trained in radiation protection at the point
      of examination shall be established for emergency cases. To realize the intended
      improvement of patient care measurements for quality assurance concerning the
      medical personnel and processes are necessary. Along with other current
      developments the basis of secure regional teleradiology networks is now built up.

PMID- 11963246
TI  - [PACS: from project to reality. Report of experiences on full digitalisation of
      the radiology department of a major hospital].
AB  - OBJECTIVE: To assess the time needed and the resulting effects of a complete
      digitalisation of a radiological department of a major hospital (856 beds, 28,000
      in-patients, 35,000 out-patients/year) a pilot study was performed. This had to
      be done without interrupting routine services. RESULTS: After intensive
      preparations were performed and the hospital-network was completed, within a two
      year period all radiological functions (mammography excluded), reporting stations
      and archives were changed to a complete digital workflow. All modalities
      (provided by 3 different companies) are now connected by DICOM-work lists. The
      picture-files (4 GB/day) are automatically routed to the work-stations (n = 10),
      where the reporting and file shows are performed, to the digital archive and to
      the peripheral viewing-stations (n = 44). The distribution of the digital
      pictures takes place all over the hospital including the ORs and special units.
      We accomplished, to connect electronically the report and the image data. The
      clinical file shows are also performed completely digitally. The access to the
      data of the deep archive is possible by the dept. of radiology without any manual
      interaction. The film consumption was reduced to an amount of less than 10%, as
      compared to the prior PACS situation. Since PACS has been introduced the
      radiological productivity increased by more than 15% and throughput-time was
      clearly reduced. CONCLUSIONS: The complete digitalisation increases productivity
      and attractiveness of a hospital-radiology and helps to shorten diagnostic and
      therapeutic decision-making. The transfer from a conventional to a digital
      workflow is possible without interrupting the clinical services. Extensive
      preparations and ongoing assistance of such projects though are clearly needed.

PMID- 11963247
TI  - [Juxtacortical tumor of the distal humerus. Periosteal Ewing sarcoma].

PMID- 11963248
TI  - [Duplex ultrasound of arteries and veins. I: Basic principles and extracranial
      arteries supplying the brain].

PMID- 11963249
TI  - [Teleradiology].

PMID- 11963250
TI  - [Teleconsultation 2001--report of the Teleconsultation Study Circle of the
      Austrian Roentgen Society (ORG)].
AB  - In 1997, the working group "Teleconsultation" of the Austrian Roentgen Society
      (ORG) has performed a first survey about the status of teleradiological
      applications in Austria. Now, in 2001, a second survey was performed in order to
      adapt the ORG's approach in this field to the most actual needs. Most of the 38
      teleradiological projects in Austria already working or shortly before
      inauguration are aiming at an improvement of the medical service in favour of our
      patients (expert consultation, image transfer to doctors requesting radiological
      examinations, clinical case discussion). However, a small but not unimportant
      fraction of teleradiology projects in Austria (11%) is performed for replacement
      of radiologists on duty, therefore for reasons mainly directed to minimising
      costs for the hospital administration. Other purposes of teleradiology projects,
      like quality assurance and medical education have even lost their small
      importance the 1997 survey already has shown. This paper discusses the
      professional implications from the results of the 2001 survey and the legal
      framework for the application of telecommunication in diagnostic radiology. The
      most important goal of all professional activities in radiology is the well-being
      of our patients, based on the immediacy of the medical profession in accordance
      with the "physician law".

PMID- 11963251
TI  - [Teleradiology--blessing or curse? 4 years routine in the North Hessia
      teleradiology data network].
AB  - Several hospitals in northern Hessen, not having their own radiology departments,
      want to run CT-scanners with the goal of improving medical quality. They
      requested co-operation from the Radiological Institute in the Hardtwaldklinik I
      in Bad Zwesten. Therefore a teleradiological network was developed, which enables
      the exchange of radiological-images and -reports between 19 hospitals today. An
      elementary requirement for this co-operation is an efficient and functional
      computer infrastructure and verified co-operation contracts. The conception,
      structure and development of the program, as well as associated difficulties are
      presented and discussed from different perspectives in the light of the
      controversy among experts. The results, experiences and benefits gained in four
      years, in which the teleradiological network of northern Hessen has been in
      place, demonstrate the importance and possibilities of teleradiology as an
      element of telemedicine. Teleradiology/telediagnostics improves the quality of
      patient care in smaller hospitals located in less-populated areas and present
      possibilities to optimize and integrate health care structures, taking economic
      considerations into account.

PMID- 11963252
TI  - [University clinics as centers of radiologic performance alliances in the
      ambulatory and inpatient sector].
AB  - PROBLEM: Health care delivery in Germany has to face severe challenges that will
      lead to a closer integration of services for in- and out-patients. University
      hospitals play an important role due to their activities in research, education
      and health care delivery. They are requested to promote and evaluate new means
      and ways for health care delivery. METHODS: The Institute of Clinical Radiology
      at the University Hospital of the Ludwig-Maximilians-University started
      teleradiological services for hospitals and general practices in January 1999 in
      the framework of the "Imaging services--teleradiological center of excellence".
      Legal, technical and organizational prerequisites were analyzed. RESULTS:
      Networks between university hospitals and general practices are not likely to
      solve all future problems. They will, however, increase the availability of the
      knowledge of experts even in rural areas and contribute to a quality ensured
      health care at the patients home. Future developments may lead to international
      co-operations and such services may be available to patients abroad. CONCLUSION:
      Legal, technical and organizational obstacles have to be overcome to create a
      framework for high quality telemedical applications. University hospitals will
      play an important role in promoting and evaluating teleradiological services.

PMID- 11963253
TI  - [Evaluation of CHILI teleradiology network 4 years after clinical
      implementation].
AB  - The CHILI teleradiology network has more than 60 installations in Germany and the
      USA. Radiological images and cardiological multiframe series are exchanged in
      clinical routine. This article investigates in what way and how often the system
      is used. This is done by means of accounting files that are produced
      automatically by the system. User functions, transmission protocols, data
      quantity, frequencies and time of data transmission and teleconferences are
      evaluated and discussed in this paper. Different application scenarios have been
      identified and are described and analyzed as well. An important result is, that
      the system is not merely an emergency system. Instead, it is used in daily
      routine as a multifunctional, multimodality workstation with advanced features
      for teleradiology and telecardiology.

PMID- 11963254
TI  - [Standards for safe data exchange in teleradiology exemplified by image and
      report distribution].
AB  - The use of telemedicine is becoming indispensable for a continuous and economical
      delivery of a high quality of care. However, data protection requirements have to
      be considered. For the selection of solutions, vendor-independent components
      based on standards are a prerequisite for a seamless integration into the
      existing, often heterogeneous, IT infrastructure. The "Internet protocol" TCP/IP
      and the DICOM standard with it's new security extensions form the basis for an
      internationally standardized and accepted procedure for a secure interchange of
      radiological images beyond platform boundaries.

PMID- 11963255
TI  - [Person. Personality. Personality disorder?].

PMID- 11963256
TI  - [Comorbidity of depressive disorders and cardiovascular diseases. Implications
      for diagnosis, pharmaco- and psychotherapy].
AB  - Controlled studies and meta-analyses show not only that depression and
      cardiovascular disease often occur together, but that depressive illnesses are an
      independent risk factor in the development and the progression of coronary heart
      disease. It can be difficult to distinguish between reactive mood disturbance
      after myocardial infarction and depressive episodes that may have preceded the
      infarction and which require treatment. Due to this difficulty, depressive
      disorders are rarely diagnosed, and only a minority of patients receive adequate
      treatment. However, owing to the introduction of new antidepressants in recent
      years, the number of treatment options has increased. Specifically, selective
      serotonin reuptake inhibitors (SSRI) offer a valuable alternative to tricyclic
      antidepressants, which are problematic in heart disease. The authors describe on
      the one hand controlled studies of SSRIs and discuss differential therapeutic
      consequences. On the other hand, studies of psychotherapeutic interventions in
      comorbid patients with depression and coronary heart disease are reported.
      Finally, the authors discuss which psychotherapeutic interventions may be
      suitable.

PMID- 11963257
TI  - [Classification and predictive quality of the "suicide intent" marker in
      parasuicides. A cluster analytic study].
AB  - The aim of the study was to investigate the discriminant and predictive quality
      of "suicide intent" (SIS) in relation to motives for deliberate self-harm (DSH).
      Cluster analysis was performed in a sample of 137 inpatients admitted to a
      psychiatric hospital after a DSH episode. Six different subgroups were isolated.
      The hypothesis was tested that the six groups would reveal distinct patterns of
      motives and different patterns of repeated DSH episodes during a 12-month
      observation period. Results indicated that one high-risk group for completed
      suicide was characterized by the highest death intention and remarkably low
      interpersonal motives. Two further groups were labeled as "moderate" risk groups.
      Two groups were found to be characterized by low suicide intent with prevailing
      patterns of distinct interpersonal oriented motives (manipulative vs
      appellative), whereas one group revealed an ambiguous motive structure reflecting
      death orientation and interpersonal motives. The DSH repetition rates were found
      to be significantly different between certain subgroups. The study results
      support the assumption that DSH patients represent heterogeneous populations with
      regard to suicide intent, motives, and the repetition of deliberate self-harm.

PMID- 11963258
TI  - [Psychiatric disorders and fitness to drive an automobile. An overview].
AB  - The revised version of the guidelines for driving ability and the new driving
      license decree in Germany are outlined regarding forensic implications, general
      rules, and guidelines for psychiatric illness. Patients suffering from acute
      organic psychosis, severe dementia, acute schizophrenia, mania, severe
      depression, and alcoholism must be seen as unable to drive cars. Regarding
      effects of psychotropic medication on driving performance, multiple data with
      healthy volunteers are available, with very few patients, however. Based on new
      data showing differences between older and newer antidepressants and
      antipsychotics, individual drug selection is strongly recommended.

PMID- 11963259
TI  - [Concept of the person in psychiatry].
AB  - At first sight, the concept of "person" appears in psychiatric terminology only
      in the negative sense, i.e., as in depersonalization. However, self-alienation
      may be regarded as the hallmark of mental illness in general and is based on the
      ambiguous structure of human personality itself. Thorough analysis of the concept
      of the person is therefore indispensable to understanding psychopathology. This
      paper focuses on the contrast of "persona" ("mask" or "role") on the one hand to
      "person" as an individual self on the other. Their dialectical relation derives
      from basic anthropological structures such as sociality, self-reference, self
      transcendence, and fictionality. As can be shown, the historical and cultural
      ontogeny of the personality includes experiences of self-alienation which may
      become relevant for psychiatry as depersonalization syndromes. The example of
      depression is used to illustrate vital and emotional depersonalization, whereas
      schizophrenia may be described as "intentional depersonalization." Following this
      line of reasoning, the classic schizophrenic experiences of alien control or
      thought insertion are interpreted as a disturbance in the fundamental personality
      structures.

PMID- 11963262
TI  - [Temperament and affective disorders. The TEMPS-A Scale as a convergence of
      European and US-American concepts].
AB  - In temperament research, three traditions can be found: (1) in psychiatry or
      psychopathology, (2) in neurobiology, and (3) in developmental psychology. After
      giving an overview, we present results and theories concerning the relation
      between temperament and affective disorders. Based on Kraepelin's concept of the
      fundamental states ("Grundszustande"), we describe four types of temperament:
      hyperthymic (manic), depressive, irritable, and cyclothymic. A fifth anxious
      temperament is added. Clinical description and scientific implications are
      described in the light of recent work by Akiskal and the German version of the
      TEMPS-A scale, a self-report questionnaire for assessing temperament.

PMID- 11963261
TI  - [Effect of personality factors and structure on the course of major depression].
AB  - The extent to which personality characteristics predict the course of severe
      depression has been controversially discussed. In a sample of 50 depressed
      inpatients, the significance of personality characteristics for the prediction of
      relapse was studied prospectively over 2 years. More than half of the patients
      studied suffered relapses within this period. Well-known predictors such as the
      number of previous episodes were confirmed. The personality characteristics
      studied showed different predictive effects at 1- and 2-year follow-up. Neurosis
      proved predictive of the 1-year course and outcome but not the 2-year course. In
      the 2nd year of follow-up, a melancholic personality structure was associated
      with favourable outcome. This personality type therefore seems to be more
      appropriate as a predictor of long-term outcome. Comparison with predictive
      factors described earlier showed that in this study, personality traits influence
      outcome independently and were not confused by other predictors. Implications for
      relapse prevention and psychotherapeutic management are discussed.

PMID- 11963260
TI  - [Personality, accentuated traits and personality disorders. A contribution to
      dimensional diagnosis of personality disorders].
AB  - A dimensional diagnostic system for personality disorders (PD) postulates
      continuous transition from normal to disordered personalities (continuity
      hypothesis) and universal validity of basic personality dimensions (universal
      hypothesis). The present study investigates the validity of Leonhard's concept of
      attenuated personalities that define a conceptual link between normal personality
      dimensions and PD. Nine possible continuous transitions between three conceptual
      levels (Big Five personality factors, nine attenuated personality traits, nine
      PD) were tested by questionnaire data obtained from a mentally healthy (n = 166)
      and a clinical sample (n = 78). Both samples differed significantly in nearly all
      variables. However, they showed substantial similarity concerning the
      (in)validity of single continua and the complex structure of all variables as
      analyzed by multidimensional scaling. The concept of attenuated personalities
      could be validated for six out of nine tested continua and can be recommended for
      application in dimensional models of personality and personality disorders.

PMID- 11963263
TI  - [Specific countertransference experience and interpersonal problem description in
      psychodynamic psychotherapy].
AB  - In psychodynamic psychotherapy, countertransference and its professional use is
      seen as an important means to identify central difficulties of patients. The
      present study examines the correspondence of countertransference and
      interpersonal difficulties in 30 therapist-patient couples in day hospital
      psychodynamic psychotherapy. Interpersonal problems were recorded using the
      inventory of interpersonal problems (IIP) and countertransference was measured
      using the impact message inventory (IMI). Correspondence was measured as the
      correlation of IIP data from the patients and IMI data from the therapists. Data
      were collected at the start of therapy, after 4 weeks of treatment, and at the
      end of treatment. Over the course of the therapy, an increase in the
      correspondence of interpersonal problems as reported by patients and
      countertransference could be observed, starting with r = 0.22 at the beginning of
      therapy and continuing through r = 0.47 after 4 weeks to r = 0.58 at the end of
      therapy. The mean correlation was slightly above that of a control group of 20
      nonclinical couples associated for at least 6 months.

PMID- 11963264
TI  - [Possibilities and limits of treatment of aggressive behavior in patients with
      mental retardation with risperidone].
AB  - Despite definite indication for psychopharmacologic intervention, severe and
      persistent symptoms of aggressive and self-injurious behaviour still remain a
      therapeutic challenge. As recent research has demonstrated, not only the
      dopaminergic and serotonergic but also the endogenous opiate system plays a role
      in the pathogenesis of self-injurious behaviour. Nevertheless, the efficacy of
      classical neuroleptics as well as opiate antagonists is questioned. In open and
      controlled studies, the administration of the atypical neuroleptic risperidone (a
      serotonin 2A-dopamine D2 antagonist) was associated with a long-term effect in
      reducing self-injuries. In our clinical trial, 20 mentally retarded adults
      presenting with severe self-injurious and aggressive behaviour were administered
      risperidone over a follow-up period of 35 months. Clinical efficacy was measured
      with the Disability Assessment Schedule (DAS), conducted in a home for people
      with mental retardation. In 17 patients, a significant reduction in self
      injurious behaviour is shown. Besides, there was a significant overall clinical
      improvement in behaviour.

PMID- 11963265
TI  - [Treatment follow-up of transsexual patients. A catamnestic study].
AB  - In a retrospective study, 33 transsexual patients, 22 male-to-female transsexual
      (MF-TS), and 11 female-to-male transsexuals (FM-TS), were interviewed 53-121
      months after their first referral to the psychiatric department of a university
      hospital. Social integration proved to be satisfactory and relatively stable.
      Twenty-five patients had gone through surgical sex reassignment, while 29 were
      currently undergoing hormonal treatment. Regarding the course of treatment, the
      FM-TS were a more homogeneous group than the MF-TS group. Overall, physical and
      psychosocial well-being was satisfactory. Psychometric measures yielded
      remarkably normal values, with some pathological findings regarding personality
      traits. In the majority of patients, self- and observer-rating appraisals of
      gender-specific physical appearance were equally positive. The results suggest a
      three-step procedure for the treatment of transsexual patients, as is practiced
      in other centers within German speaking continental Europe.

PMID- 11963266
TI  - [Paranoia with late onset. Psychopathology and psychodynamics].
AB  - We report on a 70-year-old man who suffered from persecutory delusions during the
      last 20 years. During first visits, he showed neither cognitive impairment nor
      Schneiderian first rank symptoms. Inpatient and day clinic treatment as well as
      further outpatient therapy led to reintegration into social life and trusting
      relationships between the patient and the therapeutic team, although the
      persecutory delusions still persisted. During following years, symptoms of
      cognitive impairment increased gradually and neurological symptoms could be
      observed. We present a psychodynamic hypothesis regarding the reported
      psychopathology and discuss alternative diagnoses and pharmacological treatment.

PMID- 11963267
TI  - ["How this conflict tortures me!" The man Emil Kraepelin as viewed in his poems].
AB  - In 1928, Emil Kraepelin's poems were published posthumously. They provide thus
      far unknown insight into his intellectual and emotional world. Here we meet the
      man Kraepelin rather than the psychiatrist. We feel the rather pensive mood he
      expresses using the same allegories from the world of nature again and again.
      Kraepelin suffers from the fate of his mother country and his profession as a
      doctor, which puts him in "slave chains," thus preventing him from following his
      own course and fulfilling his longings. Those can be seen in his wish to dedicate
      himself fully to his nosological, psychopathological, or experimental
      psychological research. One wonders why he did not push his aims through more
      forcefully in these areas. Procrastination became Kraepelin's self-deception,
      since he could enter those worlds periodically only. In this way, they resemble
      his journeys to the south, which became a metaphor for freedom.

PMID- 11963268
TI  - [Heautoscopy. Capgras phenomenon and rare hallucinations of own being. Comments
      on the contribution by D. Arenz].

PMID- 11963269
TI  - [Italian psychiatry after the reform of 1978].

PMID- 11963270
TI  - [The Pinel myth].

PMID- 11963271
TI  - [DGPPN "Women and Sex-Specific Questions in Psychiatry" Reference].

PMID- 11963272
TI  - [Reference for physicians in psychiatric-psychotherapeutic graduate education].

PMID- 11963273
TI  - Topics in rhythm perception and production.

PMID- 11963274
TI  - Finding downbeats with a relaxation oscillator.
AB  - A relaxation oscillator model of neural spiking dynamics is applied to the task
      of finding downbeats in rhythmical patterns. The importance of downbeat discovery
      or 'beat induction' is discussed, and the relaxation oscillator model is compared
      to other oscillator models. In a set of computer simulations the model is tested
      on 35 rhythmical patterns. The model performs well, making good predictions in 34
      of 35 cases. In an analysis we identify some shortcomings of the model and relate
      model behavior to dynamical properties of relaxation oscillators.

PMID- 11963275
TI  - A sensorimotor theory of temporal tracking and beat induction.
AB  - In this paper, we develop a theory of the neurobiological basis of temporal
      tracking and beat induction as a form of sensory-guided action. We propose three
      principal components for the neurological architecture of temporal tracking: (1)
      the central auditory system, which represents the temporal information in the
      input signal in the form of a modulation power spectrum; (2) the musculoskeletal
      system, which carries out the action and (3) a controller, in the form of a
      parieto-cerebellar-frontal loop, which carries out the synchronisation between
      input and output by means of an internal model of the musculoskeletal dynamics.
      The theory is implemented in the form of a computational algorithm which takes
      sound samples as input and synchronises a simple linear mass-spring-damper system
      to simulate audio-motor synchronisation. The model may be applied to both the
      tracking of isochronous click sequences and beat induction in rhythmic music or
      speech, and also accounts for the approximate Weberian property of timing.

PMID- 11963276
TI  - Tracking simple and complex sequences.
AB  - We address issues of synchronization to rhythms of musical complexity. In two
      experiments, synchronization to simple and more complex rhythmic sequences was
      investigated. Experiment 1 examined responses to phase and tempo perturbations
      within simple, structurally isochronous sequences, presented at different base
      rates. Experiment 2 investigated responses to similar perturbations embedded
      within more complex, metrically structured sequences; participants were
      explicitly instructed to synchronize at different metrical levels (i.e., tap at
      different rates to the same rhythmic patterns) on different trials. We found
      evidence that (1) the intrinsic tapping frequency adapts in response to temporal
      perturbations in both simple (isochronous) and complex (metrically structured)
      rhythms, (2) people can synchronize with unpredictable, metrically structured
      rhythms at different metrical levels, with qualitatively different patterns of
      synchronization seen at higher versus lower levels of metrical structure, and (3)
      synchronization at each tapping level reflects information from other metrical
      levels. The latter finding provides evidence for a dynamic and flexible internal
      representation of the sequence's metrical structure.

PMID- 11963277
TI  - Self-induced versus reactive triggering of synchronous movements in a
      deafferented patient and control subjects.
AB  - The present study investigates the contribution of tactile-kinesthetic
      information to the timing of movements. The relative timing of simultaneous
      tapping movements of finger and foot (hand-foot asynchrony) was examined in a
      simple reaction time task and in discrete self-initiated taps (Experiment 1), and
      in externally triggered synchronization tapping (Experiment 2). We compared the
      performance of a deafferented participant (IW) to the performance of two control
      groups of different ages. The pattern of results in control groups replicates
      previous findings: Whereas positive hand-foot asynchronies (hand precedes foot)
      are observed in a simultaneous reaction to an auditory stimulus, hand-foot
      asynchronies are negative with discrete self-initiated as well as auditorily
      paced sequences of synchronized finger and foot taps. In the first case, results
      are explained by a simultaneous triggering of motor commands. In contrast, self
      initiated and auditorily paced movements are assumed to be controlled in terms of
      their afferent consequences, as provided by tactile-kinesthetic information. The
      performance of the deafferented participant differed from that of healthy
      participants in some aspects. As expected on the basis of unaffected motor
      functions, the participant was able to generate finger and foot movements in
      reaction to an external signal. In spite of the lack of movement-contingent
      sensory feedback, the deafferented participant showed comparable timing errors in
      self-initiated and regularly paced tapping as observed in control participants.
      However, in discrete self-initiated taps IW's hand-foot asynchronies were
      considerably larger than in control participants, while performance did not
      differ from that of controls in continuous movement generation. These findings
      are discussed in terms of an internal generation of the movement's sensory
      consequences (forward-modeling).

PMID- 11963278
TI  - The impact of metrical structure on performance stability in bimanual 1:3
      tapping.
AB  - Participants performed a three-beat (strong-weak-weak) finger-tapping pattern
      with one hand while synchronizing taps of the other hand with either the strong
      tap (metrically congruous rhythm) or one of the weak taps (metrically incongruous
      rhythms). We tested the hypothesis that performance would be less stable during
      the production of the incongruous rhythms. The tapping sequences were performed
      at two different tempi (Experiment 1) and under two different cognitive
      descriptions of the task (Experiment 2). Metrically incongruous rhythms showed
      greater force differentiation between strong and weak taps, increases in the
      variability of the timing within and between hands, and frequent breakdowns of
      the between-hand coordination. Tempo variations and the different cognitive
      descriptions of the task did not influence performance. We suggest that the
      difficulty in producing incongruous rhythms arises from interference between the
      required incongruous metric pattern and a spontaneously available pattern in
      which the potential boundary-markers of the metric units systematically coincide.

PMID- 11963279
TI  - The contribution of tactile reafference to temporal regularity during bimanual
      finger tapping.
AB  - In a repetitive tapping task, the within-hand variability of intertap intervals
      is reduced when participants tap with both hands, as opposed to single-handed
      tapping. This bimanual advantage can be attributed to timer variance (according
      to the Wing-Kristofferson model). Separate timers have been proposed for each
      hand whose outputs are then averaged (Helmuth & Ivry, 1996, Journal of
      Experimental Psychology: Human Perception and Performance, 22, 278-293).
      Alternatively, timing might be based on sensory reafference and the bimanual
      advantage due to the enhancement of sensory reafferences. This alternative
      hypothesis was tested in three experiments. In the first experiment, we
      replicated the bimanual advantage in tapping with two fingers of the same hand
      compared with single finger tapping. In the second experiment, we demonstrated
      that the bimanual advantage decreased when tactile reafferences from left-hand
      taps were omitted (by contact-free tapping). In the third experiment,
      participants tapped bimanually with the index fingers of both hands firmly
      mechanically coupled. The bimanual advantage was replicated for this condition.
      Results are consistent with the assumption that the bimanual advantage is due to
      the sensory reafferences of the second hand. We suggest that our results are best
      explained by a reformulation of the Wing-Kristofferson model, in which the timer
      provides action goals in terms of sensory reafferences.

PMID- 11963280
TI  - Effects of delayed auditory feedback on timing of music performance.
AB  - Three experiments examined effects of delayed auditory feedback (DAF) on music
      performance as a function of the temporal location of feedback onsets within
      produced inter-onset intervals (IOIs). In Experiment 1, pianists performed
      isochronous melodies at two production rates with different amounts of DAF.
      Timing variability decreased for DAF amounts that caused feedback onsets to occur
      halfway through IOIs (binary subdivisions) in a 500-ms, but not 600-ms, IOI rate
      condition. In Experiment 2, pianists performed melodies with DAF delays and chose
      a preferred rate. Performers chose slower rates for larger delays; preferred
      rates approximated twice the amount of DAF. Experiment 3 tested the possibility
      that subjects deliberately conceptualized subdivisions in Experiments 1 and 2.
      Performers were given (1) no instructions, (2) instructions to mentally subdivide
      produced events in two, or (3) instructions to mentally subdivide produced events
      in three, in different blocks. Instructions to subdivide reduced timing
      variability for larger feedback delays. These experiments indicate that DAF
      disruption is reduced by subdividing instructions and sometimes by coincidences
      of feedback onsets with subdivisions of produced intervals. Such facilitation may
      reflect the use of hierarchical cognitive plans in production.

PMID- 11963281
TI  - The role of practice and automaticity in temporal and nontemporal dual-task
      performance.
AB  - Research on time and attention shows that a nontemporal task may interfere with a
      concurrent timing task by making time judgments shorter, more variable, and/or
      more inaccurate compared to timing-only conditions. Brown (1998, Psychological
      Research, 61, 71-81) counteracted the interference effect by giving subjects
      automaticity training on a nontemporal task to reduce the amount of processing
      resources the task required. Such practice attenuated interference in timing. Two
      new experiments were designed to replicate and extend the previous findings.
      Subjects generated a series of 5-s temporal productions under single-task (timing
      only) and dual-task (timing plus nontemporal task) conditions. The nontemporal
      tasks were pursuit rotor tracking (Experiment 1), and mirror-reversed reading
      (Experiment 2). We employed a pretest-practice-posttest paradigm, with the
      practice sessions devoted to performance of the nontemporal task. Pretest
      posttest comparisons showed that practice reduced interference in timing in both
      experiments. Dual-task probe trials were given during the practice sessions to
      trace the time course of the improvement in timing. The results showed that
      interference in timing was reduced with even small amounts of practice. The
      findings support the idea that timing is very sensitive to changes in the
      allocation of attentional resources.

PMID- 11963282
TI  - Non-invasive evaluation of central venous pressure by echocardiography.
AB  - INTRODUCTION: Central venous pressure (CVP) is an important hemodynamic
      parameter, reflecting the patient's volume status. Although some studies of non
      invasive evaluation of CVP by echocardiography exist, an exact quantitative
      method has not been described. OBJECTIVES: Analyzing several echocardiographic
      variables, the authors present an equation to calculate CVP with good statistical
      correlation with CVP measured invasively. MATERIAL AND METHODS: The study
      included 45 patients, 32 undergoing mechanical ventilation, 32 in sinus rhythm
      and 13 with atrial fibrillation. Patients underwent simultaneous CVP measurement
      and transthoracic Doppler echocardiography. Statistical analysis was performed
      using bivariate correlation and analysis of variance. RESULTS: Several
      echocardiographic parameters measured showed a good correlation with the measured
      CVP. Standardized coefficients were applied to them and an equation to calculate
      CVP was obtained (tricuspid E decelaration) x 0.11 + (RU/RA gradient) x 0.16 -
      (IVC variation). CONCLUSION: This new method seems reliable to evaluate non
      invasively a hemodynamic parameter that until now has only been measured
      approximately by this approach.

PMID- 11963283
TI  - Doppler echocardiography in non-invasive evaluation of central venous pressure.

PMID- 11963284
TI  - Cardiovascular effects of cyclosporin treatment in an experimental model.
AB  - OBJECTIVE: This work aims to study the cardiovascular and renal effects of
      cyclosporin treatment. This purpose was achieved by using an animal model treated
      with cyclosporin in doses equivalent to the Cmin and Cmax values from human
      pharmacokinetics. METHODS: Wistar rats, weighing between 300 and 400 g, were
      treated with cyclosporin (Sandimmune Neoral) for 7 weeks. The cyclosporin was
      diluted in orange juice and administered in two doses: 5 and 30 mg/kg/day. The
      control group received only orange juice. Blood pressure was evaluated by the
      tail-cuff method and an ECG was also performed. Besides blood cyclosporin levels,
      CPK, LDH, SGPT, SGOT, sodium, potassium and creatinine in serum and protein in
      urine, as well as plasma lipids (triglycerides, total and HDL cholesterol), were
      measured. RESULTS: Both doses of cyclosporin increased blood pressure but only 30
      mg/kg/day induced tachycardia. Changes in electrocardiographic profile were also
      observed: an increase in QTc as well as an increase in T wave amplitude. Thus,
      the group treated with 30 mg/kg/day of cyclosporin showed an ischemic heart
      disease electrocardiographic profile which was reinforced by increased CPK, SGPT
      and SGOT but with no changes in LDH values. None of the cyclosporin-treated rats
      presented cardiac hypertrophy. Despite the increase in plasma lipids there was
      little or no increase in body weight, which was most evident in the group that
      received 30 mg/kg/day of cyclosporin. No alterations were observed in serum Na+,
      K+ or creatinine values or in urine protein levels. CONCLUSIONS: Our results
      showed that the cardiovascular effects of cyclosporin in Wistar rats are
      characterized by arterial hypertension, ischemic heart disease and tachycardia,
      but not cardiac hypertrophy. However, when these changes occur, kidney function
      seems to be normal. These facts suggest that cyclosporin-induced cardiovascular
      changes, particularly hypertension, are prior to renal damage. Moreover, our
      cyclosporin-induced hypertension model could be useful to study drugs that could
      treat or prevent these changes.

PMID- 11963285
TI  - [Neurohumoral activation, regulation of sodium excretion and vasodilator
      treatment in heart insufficiency].
AB  - BACKGROUND: The benefits of vasodilator therapy guided by hemodynamic goals in
      patients with severe heart failure (HF) are well documented. Nevertheless,
      therapy induced arterial underfilling may activate compensatory neurohumoral
      mechanisms and sodium retention. OBJECTIVES: To evaluate the effect of
      vasodilator therapy on neurohumoral activation and sodium excretion in severe HF
      patients submitted to tailored therapy guided by hemodynamic parameters. METHODS:
      Ten male patients (aged 70.2 +/- 2.9 years) with severe HF (left ventricle
      ejection fraction = 15.2 +/- 1.1%) were evaluated according to hemodynamic
      parameters and plasma levels of brain natriuretic peptide (BNP), norepinephrine,
      aldosterone, plasma renin activity (PRA), sodium and creatinine and urinary
      levels of sodium and creatinine, prior to beginning of nitroprusside therapy,
      every six hours thereafter (for 24 hours) and again after five days of inhibition
      of angiotensin converting enzyme (ACE) with lisinopril. RESULTS: Nitroprusside
      therapy caused marked increase in cardiac index and substantial reduction in
      systemic vascular resistance index. Plasma levels of BNP failed significantly
      while those of PRA, aldosterone and norepinephrine markedly rose, causing
      substantial reduction of sodium urinary excretion. There were no changes in renal
      function. Following ACE inhibition by lisinopril, BNP and sodium plasma levels
      rose, but BNP values remained significantly lower than the initial ones.
      Norepinephrine and aldosterone returned to base levels and PRA rose sharply.
      There was an intense natriuretic response and significant elevation of urinary
      volume. Urinary creatinine and creatinine clearance decreased non-significantly.
      CONCLUSIONS: Our results show that intensive vasodilator therapy in patients with
      severe HF improves hemodynamic parameters and causes activation of renin
      angiotensin-aldosterone and adrenergic systems, resulting in sodium retention.
      Nevertheless, this neurohumoral activation is reversed by ACE inhibitors, thus
      supporting the "wide spectrum" neurohumoral modulation role attributed to these
      drugs.

PMID- 11963286
TI  - [Biohemorheologic factors and cardiovascular events curve in survivors of
      transmural acute myocardial infarct--24-month follow-up].
AB  - INTRODUCTION: Previous reports have shown several biohemorheological disturbances
      in acute myocardial infarction (AMI), either in the acute phase and after
      hospital discharge. There is no clearly established relationship between these
      parameters and the patients' clinical outcome. OBJECTIVE: To evaluate in
      transmural AMI survivors, a relationship between biohemorheological parameters
      and the cardiovascular events curve during a 24 month follow-up period. METHODS:
      Sixty-four consecutive patients (58.0 +/- 12.0, 59 men), transmural AMI survivors
      (30 anterior and 34 inferior) were included in the study. Clinical follow-up was
      24 months (at 6, 12 and 24 months). The following cardiovascular events (CVE)
      were collected: cardiovascular death, stroke, AMI, unstable angina, embolism. We
      determined, at hospital discharge, these biohemorheological parameters: plasma
      viscosity, fibrinogen, PAI-1 inhibitor, leukocyte count, C protein (C Pt),
      erythrocyte aggregation (EA). For each parameter we determined the 25, 50 and 75
      percentiles and other significant cut-off point, grouping patients according to
      these values. STATISTICS: Group t test, Kaplan-Meier survival curve (with the log
      rank test), and Cox logistic regression. RESULTS: (1) Patients with CVE (n = 19)
      during the 24 months of clinical follow-up had at hospital discharge higher
      leukocyte count (p < 0.001), lower C Pt (p < 0.01) and lower EA (p < 0.05). (2)
      The higher the percentile of the leukocyte count higher the probability for a
      CVE. Patients with leukocyte count above the 50 percentile had 6 times more CVE
      (p < 0.01); (3) The higher the C Pt lower the risk for a CVE. Patients with C PT
      lower than the 50 percentile had 9 times more risk for a CVE (p < 0.01), and
      those above the 75 percentile had no CVE (p < 0.01). (4) For the EA we identified
      a cutoff point (= 14.5), independent of the percentiles values. Patients with EA
      below 14.5 had six times more CVE. By multivariate analyses, we identified
      leukocyte count and C Pt as independent risk predictive factors (p < 0.05).
      CONCLUSION: In this group of transmural MI survivors a relationship was
      established between some biohemorheological (leukocyte count, C Pt, EA) and the
      CVE curve during 24 months of clinical follow-up.

PMID- 11963287
TI  - [Pulmonary hypertension. Topic review. 2 clinical cases].
AB  - The authors describe two cases of pulmonary hypertension (PHT). In the first case
      it is secondary to pulmonary thromboembolism, a frequent and serious occurrence,
      witch is well known as a cause of PHT. In the second case the PHT is probably
      secondary to infection by human immunodeficiency virus, also a serious and
      frequent condition in clinical practice but which was only recently identified as
      a cause of PHT. Formerly these patients were considered as suffering from primary
      PHT. The authors make a brief review of the literature on pulmonary hypertension.

PMID- 11963288
TI  - Update of the management of venous thromboembolism.
AB  - Venous thromboembolism is the third most common cardiovascular disease. Its
      treatment is based in unfractionated heparin (UFH), but the advance of low
      molecular weight heparins, with clinical efficacy at least similar to UFH and
      better safety profile, have changed the therapeutic consensus. The highly
      relevant physiopathologic information has contributed to understand the
      paradoxical thrombotic mechanisms associated with heparin induced
      thrombocytopenia. New drugs, such as danaparoid sodium, lepirudin and argatroban,
      are an alternative to anticoagulation by heparin when this adverse reaction
      occurs. Another relevant progress was the determination of optimal duration of
      oral anticoagulation in order to prevent thromboembolic recurrences. In the
      meantime, other pharmacological approaches (thrombolytics and antiplatelet
      agents) have been assessed in several trials of limited value outcomes.
      Prophylactic measures like graduated compression stockings/intermittent external
      pneumatic compression and inferior vena cava filters have shown efficacy in
      primary and secondary prevention in patients with different risks of
      thromboembolic recurrence.

PMID- 11963289
TI  - [Smoking cessation: evidence-based recommendations].
AB  - Smoking is an important cause of morbidity and mortality, and is considered the
      most important preventable cause of disease and death in the developed world. It
      is a cause of cancer, heart disease, stroke, chronic obstructive pulmonary
      disease and pregnancy complications. Even though smoking is known as an important
      health hazard, tobacco use remains surprisingly high. In Portugal, 18% of the
      adult population smokes, and the prevalence of adolescent smoking has risen
      dramatically during the 90s. A significant percentage of actual smokers are
      willing to quit, creating a major responsibility for health care providers.
      Cardiologists bear a special responsibility, because there is good observational
      evidence that patients with coronary disease that quit smoking significantly
      lower their risk of recurrent ischemic events or death, and patients with
      peripheral vascular disease or stroke also get benefits, with better exercise
      tolerance, diminished rates of limb amputation, increased survival and less
      stroke recurrence. We wrote this paper to summarize the main recommendations on
      techniques of smoking cessation, based on evidence-based recommendations.

PMID- 11963290
TI  - Value of isolating the pulmonary veins in the treatment of atrial fibrillation.
      Sinus rhythm recovery after pulmonary vein isolation and persistent fibrillation
      inside the disconnected pulmonary veins.

PMID- 11963291
TI  - Postoperative complications of heart valve surgery.

PMID- 11963292
TI  - [Tissue doppler imaging consistently defects myocardial abnormalities in patients
      with hypertrophic cardiomyopathy and provides a novel means for an early
      diagnosis before and independently of hypertrophy].

PMID- 11963293
TI  - [Our cytochrome P450: a waste-disposal enterprise much in demand].

PMID- 11963294
TI  - [The use of the infraclavicular plexus catheter for treatment of perioperative
      and chronic pain].
AB  - OBJECTIVES: The aim of this prospective study was to evaluate the vertical
      infraclavicular approach to the brachial plexus for the insertion of a catheter
      to achieve continuous analgesia in postoperative patients and patients with
      chronic upper limb pain. METHODS: The brachial plexus was identified using the
      technique described by Kilka et al. and a flexible catheter (diameter 0.85 mm)
      was introduced 3-5 cm into the perineural sheath via the punction cannula.
      Regional analgesia was achieved by intermittent injection of local anaesthetic
      agent. Placement of the catheter, duration and effectiveness of treatment,
      complications and reasons for catheter removal were recorded using a standard
      protocol. RESULTS: A total number of 226 plexus catheters were placed in 210
      patients. Consecutive regional analgesia for at least 48 h was possible in 88%.
      Analgesia was sufficient in 76% of patients up to the time of catheter removal.
      The median (minimum-maximum) duration of catheterisation in the whole collective
      was 7 days (1-240) and 11 days in patients with chronic pain. Almost 30% of the
      patients were treated for 10 days or longer and 4.4% were treated for 1 month or
      longer. Major complications occurred in only three cases, while technical
      problems and minor complications (redness at puncture site) occurred in 10% of
      cases. CONCLUSIONS: The placement of an infraclavicular plexus catheter is a
      suitable method for pain management in the upper limb. This approach may have
      advantages in patients with severe injuries who cannot abduct the arm. Our
      results are encouraging in terms of catheterisation time, patient comfort and
      incidence of complications.

PMID- 11963295
TI  - [Cytochrome P450 enzymes and their role in drug interactions].
AB  - One of the factors that can alter the response to drugs is the concurrent
      administration of other drugs. There are several mechanisms by which drugs may
      interact, but most can be categorised as pharmacokinetic (absorption,
      distribution, metabolism, excretion), pharmacodynamic, or combined toxicity.
      Knowledge of the mechanism by which a given drug interaction occurs is often
      clinically useful and may help to avoid serious adverse events and perioperative
      morbidity. Although every tissue has some ability to metabolise drugs, the liver
      is the principal organ of drug metabolism and at the subcellular level the
      cytochrome P450 enzyme system is the main source of drug interaction. This
      article reviews the basic principles of drug metabolism and the role of
      cytochrome P450 in this scenario. Drugs frequently used in anaesthesia and
      critical care medicine such as benzodiazepines, opioid analgesics,
      antihypertensive and antiarrhythmic agents, antibiotics and antifungal drugs,
      antiemetics, histamine-receptor-antagonists, theopylline and paracetamol will be
      considered. The development of methods and tools which are practical and also
      economic, are of utmost importance since drug interaction is predictable if the
      metabolic pathway and the activity (genetic polymorphism) of the enzyme is known.

PMID- 11963297
TI  - [Opioid rotation in pain therapy. Case report].
AB  - The use of opioids in the treatment of chronic pain is sometimes accompanied by
      inadequate pain relief and opioid-specific side-effects. Opioid rotation is a
      therapeutic approach, that can improve analgesia and provide a more advantageous
      analgesia and toxicity relationship. This article presents a case report and
      discusses the mechanisms, indications and possibilities of opioid rotation.

PMID- 11963296
TI  - [Long-term results after surgical tracheotomy and percutaneous dilatation
      tracheostomy. A comparative retrospective analysis].
AB  - Besides surgical tracheostoma for treatment of long-term intubation, percutaneous
      dilatational tracheostomy (PDT) has become available during the last few years.
      Long-term results of the PDT are rare in the medical literature. This paper
      reports a retrospective analysis comparing the results after PDT with those after
      surgical tracheostomy. The methods include subjective evaluation of both
      techniques by the patients using a standardized questionnaire. It also includes
      the objective cosmetic result of the outside scar, as well as endoscopic
      inspection of the larynx and trachea. The patients own evaluation showed a higher
      content in the PDT group mainly due to the cosmetic result. The objective data
      confirmed those results. Patients with surgical tracheostomy had an average scar
      length of 5 cm (2 inches), compared to 1,2 cm (5 inch) in the PDT group. The
      endoscopic examination showed minor stenosis of the trachea in both groups that
      were not functionally relevant. The average stenosis of 14% for the PDT was
      similar to that observed after surgical tracheostomy which was 19%. The choice of
      the best technique should be made in close cooperation between head- and neck
      surgeons and anesthesiologists.

PMID- 11963299
TI  - [The law on advertisement of medical products and the practicing physician. An
      introduction to the problems].

PMID- 11963298
TI  - [Non-invasive ventilation. Consensus statement on indications, possibilities and
      use in acute respiratory insufficiency].

PMID- 11963300
TI  - [Neonatal assessment and resuscitation. Current guidelines of the ICOR Pediatric
      Working Group].

PMID- 11963301
TI  - [Obstetric analgesia and anesthesia in Switzerland in 1999].
AB  - QUESTION: This survey investigated the common practice of obstetric analgesia and
      anaesthesia in Swiss hospitals and evaluated the influence of the Swiss interest
      group for obstetric anaesthesia. METHODS: In March 1999 we submitted 145
      questionnaires to all Swiss hospitals providing an obstetric service. RESULTS:
      The rate of epidural analgesia (EA) was higher in large hospitals (> 1,000
      births/year) than in small services. EA was maintained by continuous infusion
      techniques in 53% of the responding hospitals. For elective caesarean section,
      spinal anaesthesia (SA) and EA were performed in 77% and 16% of the patients,
      respectively. General anaesthesia (5%) was only used in small hospitals (< 500
      births/year). Emergency caesarean section was performed under SA in 75% of all
      hospitals and only in 25% was a general anaesthesia used. An already existing EA
      for labour analgesia was continued for anaesthesia for caesarean section in 63%
      of Swiss hospitals. CONCLUSIONS: Regional anaesthesia was most commonly used for
      obstetric anaesthesia in Swiss hospitals. Epidemiological studies,
      recommendations of the Swiss interest group for obstetric anaesthesia, as well as
      the expectations of pregnant women, increased the numbers of regional anaesthesia
      compared with the first survey in 1992.

PMID- 11963302
TI  - [Participation--oriented analysis of the anesthesia workplace. A work system for
      anesthesia in a multidisciplinary operating room].
AB  - INTRODUCTION: The aim of this study was the detection and understanding of weak
      points in the ergonomic design of anaesthesia workplaces in a multidisciplinary
      operating room facility. METHODS: Analysis of workplaces and of working processes
      by means of observations, computer-supported task recording and video-photo
      documentation. During guided interviews the participants were provided with
      material for naming-by-pointing and drawing. Subsequently, the background of the
      problems encountered and possible improvements were visualised. RESULTS:
      Important deficits were devices not positioned within reach and view,
      difficulties in operating the lines connecting the patient and the devices, and
      inconsistent workplace layouts. These were caused by erroneous planning of the
      facility and disregarding ergonomic principles in equipment design. The initial
      improvements implemented were the development of a new concept for a flexible
      equipment positioning and the design of a tool for cable handling. DISCUSSION AND
      CONCLUSION: Although from the very beginning of the study the anaesthesia
      personnel quoted the handling of the lines connecting patients and devices as the
      main cause for working difficulties, the external ergonomist could contribute to
      a broader view of the problems. The method presented here initiated a mutual
      learning process between ergonomist and users and resulted in a common
      understanding of the problems and their causes. Compared to the traditional
      consulting process, more time and efforts were necessary but were offset by the
      users' acceptance of the improvements and the prevention of design errors.

PMID- 11963303
TI  - [Transesophageal echocardiography and intraoperative management of patients with
      renal cell carcinoma and rena cava extension].
AB  - OBJECTIVE: To evaluate the role of intraoperative real-time transesophageal
      echocardiography (TEE) for the anesthetic and surgical management of patients
      with renal cell carcinoma and vena cava extension. METHODS: Retrospective
      analysis of the intraoperative application of TEE in a series of 4 patients.
      RESULTS: Real-time TEE with a multiplane probe allowed visualization of inferior
      vena cava tumor extensions, accurate assessment of the distal extent of vena cava
      invasion into hepatic veins and right atrium, monitoring of embolism and
      evaluation of cardiac preload and function in all patients. CONCLUSION:
      Intraoperative TEE is a useful adjunct to the anesthetic and surgical management
      of patients with renal cell carcinoma and vena cava extension.

PMID- 11963304
TI  - [Color duplex sonographic findings in an iatrogenic arteriovenous fistula of the
      vertebral artery].
AB  - The report describes a rare case of an iatrogenic arteriovenous fistula of the
      vertebral artery to the vertebral vein which arose after insertion of a central
      venous catheter via the jugular vein. We give special attention to the role of
      colour duplex sonography in the primary diagnosis of such fistulas. As can be
      seen from published reports with this non-invasive examination, the diagnosis of
      fistulas could not be established in all cases, where an abnormal communication
      between the vessels was later revealed by angiography. The most probable reason
      is the particular feature of the anatomical course of the vertebral artery which
      in its middle third is protected in a bony canal through the foramina
      transversaria of the cervical vertebrae and can be only partially visualised by
      sonography. Consequently only fistulas in the visible parts of the artery can be
      detected by sonography. In our case the most important criteria of duplex
      sonography for an arteriovenous fistula were fulfilled and the diagnosis was
      confirmed by angiography. This procedure with primary use of colour duplex
      sonography and additional clarification of uncertain findings by angiography,
      seems to be reasonable if the symptoms are compatible with the diagnosis of an
      arteriovenous fistula of the neck vessels.

PMID- 11963305
TI  - [Tracheostomy. Indications, methods, risks].
AB  - Tracheostomy is one of the oldest procedures in surgery. Although it was
      traditionally used for treatment of upper airway stenosis, the primary surgical
      indication is now in the long-term intensive care unit patient. Here, the aims
      are avoidance of damage to the larynx, earlier weaning from artificial
      respiration and improved nursing care. Apart from the conventional operating
      method, minimally invasive procedures have been increasingly employed. More than
      20,000 ICU patients per annum are now treated in Germany by these modern methods.
      Common features of these procedures are the initial puncture of the trachea with
      subsequent dilatation of the puncture channel. Current meta-analyses of
      prospectively randomised studies show a lower complication rate than with
      conventional methods. Furthermore, serious sequelae such as tracheal stenosis are
      rare in the long-term course. However, conventional operative tracheostomy still
      has its place, particularly in circumstances where the new methods are
      contraindicated.

PMID- 11963306
TI  - [Plasma cholinesterase variations as a result of prolonged neuromuscular
      blockade. Review and problems encountered in two cases of prolonged neuromuscular
      blockade after muscle relaxation with succinylcholine as compared to mivacurium].
AB  - Succinylcholine and mivacurium are degraded more slowly in patients with a
      qualitatively or quantitatively reduced plasma cholinesterase and are therefore
      known for inducing a prolonged postoperative apnea. Perioperative laboratory
      screening even including plasma cholinesterase activity testing will not prevent
      this due to a possible aberration only in the qualitative cholinesterase
      activity. This is illustrated by introducing two cases reports of prolonged apnea
      after administration of mivacurium or succinylcholine. The pathophysiology of
      plasma cholinesterase is reviewed including genetically determined variants and
      the degradation pathways of mivacurium and succinylcholine. Only extensive
      laboratory chemical tests are sufficient to prevent this possible complication.
      Due to the rare incidence there is no evidence for recommending these laboratory
      investigations in all patients. Once prolonged apnea occurs following the
      administration of mivacurium or succinylcholine the best choice is ongoing
      ventilation combined with a sufficient sedation.

PMID- 11963307
TI  - [Working time law and personal liability. Legal judgements about on-call duty and
      work schedules].

PMID- 11963308
TI  - [Anesthesia for endoscopic surgery].

PMID- 11963309
TI  - Perioperative transesophageal echocardiography for cardiac surgery. A fleeting
      trend or standard of care?

PMID- 11963311
TI  - CHI. Who nose best? Commission for Health Improvement.
AB  - CHI is the fastest growing institution in the NHS. It has been generally well
      accepted by the NHS. Its methodology is a compromise between looking at
      mechanisms and testing whether they deliver in practice. There is no consistency
      in the basic data provided in CHI reports. It remains to be seen what effect CHI
      reports have on improving patient care.

PMID- 11963312
TI  - NHS morale. Singing the blues.
AB  - Focus groups of clinical directors, managers, doctors and nurses felt morale and
      motivation were generally low in their organisations. They thought staff no
      longer felt valued by politicians and that this had affected the public's
      perception of the NHS. A mismatch between central initiatives and what the local
      service required was seen as a source of stress. A sense of being valued was seen
      as the key motivator for staff.

PMID- 11963310
TI  - [Transesophageal echocardiography: perioperative evaluation of valvular
      function].
AB  - Since its introduction into the operating room, transesophageal echocardiography
      (TEE) has proven to be an invaluable diagnostic tool for perioperative patient
      management. TEE allows direct visualization of structural and functional cardiac
      abnormalities. Therefore, it has become the most important imaging technique to
      evaluate valular function. Pressure gradients across a stenotic valve can be
      calculated by measuring the blood flow velocity within the valve. Additionally,
      the area of the valve can be estimated by using the continuity equation. The
      severity of regurgitant blood flow across an incompetent valve can be assessed
      using color flow, continuous or pulsed-wave Doppler. Surgical patients experience
      significant changes in blood pressure, intrathoracic pressures and volume status
      in the perioperative period. Therefore, the interaction between these parameters
      and valvular function is the focus of recent clinical studies and might in future
      contribute to the perioperative as well as anesthesiological management of
      patients with valvular dysfunction.

PMID- 11963313
TI  - Hospital readmissions. Return to sender.
AB  - A study of elderly patients who were repeatedly readmitted to an acute hospital
      found many admissions could be averted by providing more intense, alternative
      care. Many admissions were made by on-call GPs who did not know the patients'
      case. Some discharges appeared to have been premature. More attention needs to be
      given to preventive care, and greater use made of community nurses as the focal
      point of a support system. The study has highlighted the need for pooled budgets
      between health and social services.

PMID- 11963315
TI  - Open space. Burden of proof.

PMID- 11963314
TI  - Patient involvement. Hearing voices.
AB  - The government's proposals for public and patient involvement in the NHS seem
      more robust than the current structures. They involve a greater degree of
      accountability. They represent some consensus among health consumer groups.

PMID- 11963316
TI  - Myalgic encephalomyelitis. Talking to ME.

PMID- 11963317
TI  - Managers & medicine. At the heart of the matter.

PMID- 11963318
TI  - Managers & medicine. Cardiac arrested?

PMID- 11963319
TI  - Data briefing. Long-term care.

PMID- 11963320
TI  - The human genome project and its implications.

PMID- 11963321
TI  - Anthelmintics: a review.
AB  - Helminths infect 25% of the world's population. In the last 50 years specific,
      safe and effective anthelminitic drug therapy for various parasitic infestations
      have been developed. The population of the developing countries across the globe
      suffers not only as a direct result of these infections but due also to co
      morbidity such as anemia, malnutrition and reduced immunity status. Earlier
      anthelmintic drugs suffered from serious drawbacks such as hepatotoxicity and
      required specific preparation of the patient before treatment such as 12-hour
      fasting and pre-post purging caused considerable inconvenience to the patient.
      However, successive discoveries were born out of rationale approach that
      contributed to the effective, more specific and more easily tolerated drugs i.e.
      benzimidazoles, piperazine derivatives, avermectins, pyrazinoquinoline, etc. The
      present approach is to identify the causative parasite on the basis of stool
      examination and as a result of this approach, different drugs are prescribed for
      different parasitic infections. Examples include thiabendazole for cutaneous
      larva migrans, mebendazole for ascariasis, trichiuriasis and hookworm,
      albendazole for inoperable cases of cystic hydatid disease, DEC for Toxocara
      induced visceral larva migrans and loiasis, ivermectin for onchocerciasis,
      praziquantel for schistosomiasis and niridazole for Dracunculus medinensis. The
      cure rates with these drugs is also high e.g. thiabendazole produces a cure-rate
      of 98% in cutaneous larva migrans while mebendazole gives cure rate of 76-95% in
      ascariasis, trichiuriasis and hookworm infestations. A cure rate of 96% is
      produced by praziquantel in schistosomiasis. Most of these drugs have broad
      spectrum anthelmentic effect. The present review aims at evaluating the currently
      available anthelmintics with respect to their efficacy and adverse effects. Steps
      to prevent impending helminthic drug resistance are also discussed.

PMID- 11963322
TI  - Pancreatico-biliary ductal union.
AB  - A long common channel distal to the pancreaticobiliary junction is the commonest
      anomalous arrangement of the pancreaticobiliary ductal system and is mostly
      observed in patients with congenital choledochal cysts. APBDU without choledochal
      cyst is a high-risk condition for the development of gallbladder carcinomas.
      Prophylactic excision of the extrahepatic biliary system and reconstruction of
      the biliary tract with hepatico-jejunostomy are recommended. APBDU should always
      be kept in mind when a patient with a long history of abdominal pain is found to
      have gall bladder wall thickness even without gallstones on imaging by a CT Scan
      or Ultra Sound. ERCP should be performed in these patients in order to detect
      APBDU. This may allow early detection of carcinoma of the biliary tract. Presence
      of common channel may be associated with a lower incidence of gallstones. However
      it requires corroboration by other studies. On the other hand carcinoma of the
      gall bladder appears to have a close association with abnormally long common
      channel.

PMID- 11963323
TI  - Symptom score does not correlate with gastritis grade and Helicobacter pylori
      infection in non ulcer dyspepsia.
AB  - BACKGROUND: Non ulcer dyspepsia (NUD) is being postulated as one of the
      gastroduodenal manifestations of H. pylori infection. H. pylori infection may
      result in clinical symptoms as well as histological changes in NUD. AIM: To
      compare clinical symptom score and histological changes in H. pylori (Hp)
      positive and negative untreated NUD patients. METHODS: Forty six patients with
      dyspeptic symptoms and normal upper GI endoscopic examinations were included in
      this study. During endoscopy 2 biopsies each were taken from the antrum and body
      of the stomach. These biopsies were used for rapid urease test (RUT) and
      histological examination. Patients were diagnosed to have Hp infection if either
      of two tests were positive. There were two groups of patients: Hp positive and Hp
      negative NUD patients. Clinical scoring using Glasgow dyspepsia score (Max. 20)
      and histological analysis, using Sydney system (Max score 11) was done and
      compared for both the groups of patients. Clinical scoring, RUT and histological
      scoring were blinded to each other. RESULTS: H. pylori was present in 29(63%) of
      the 46 patients. Mean clinical score for H. pylori positive patient was 10.9
      while for Hp negative patient was 11.4. Total histological score for Hp positive
      and Hp negative patients was 3.37 Vs 1.76 (antrum) and 3.68 Vs 1.29(body) (p <
      .001), respectively. The only histological change found to be statistically
      significant between Hp positive and Hp negative patients was presence of lymphoid
      follicles (p < .05). CONCLUSION: Clinical scoring does not correlate with the
      presence of H pylori or histological severity. In NUD patients positive for H.
      pylori, there is a significant increase in the severity of gastritis both in the
      antrum and the body.

PMID- 11963324
TI  - Gross anatomy of the pancreatic ducts in north Indians.
AB  - Gross anatomy of the pancreatic ducts was studied in dissections and by preparing
      corrosion casts of pancreases, obtained from 218 male and 57 female adult
      cadavers. In addition 72 normal pancreatograms were also examined. The main
      pancreatic duct (MPD) started as two or more tributaries in the tail of the
      pancreas and crossed the body of the 12th dorsal or the first lumbar vertebra or
      in between in 72.5% males and 62.5% females. In 96% specimens MPD followed the
      usual course and opened at the major duodenal papilla. Twenty to thirty five
      lobular ducts opened on either side of the MPD while a few opened on the anterior
      or posterior walls. There was no 'herringbone' arrangement. The distance between
      the two ductules varied from 1 to 10 mm. Mode of formation of the accessory
      pancreatic duct (APD), its course and termination were also studied. In dissected
      specimens the embryonic type of pancreatic duct (pancreas divisum) was seen in 9
      (4.5%) male and 3 (6%) female specimens. In 15.1% male and 26.3% female (p <
      0.05) subjects APD will not act as a safety valve if an obstruction occurs in the
      distal part of MPD.

PMID- 11963325
TI  - Lactose intolerance in different types of irritable bowel syndrome in north
      Indians.
AB  - BACKGROUND: Twenty-five patients of irritable bowel syndrome (IBS) and 25 normal
      healthy individuals serving as controls, were studied for lactose intolerance.
      METHODS: Hydrogen breath test was used as an investigation after giving 50 g of
      oral lactose. Clinically, the patients were classified into 3 types of IBS.
      RESULTS: Eleven (44%) out of 25 patients belonged to diarrhoeal type of IBS, 7
      (28%) of 25 patients to spastic and rest 7 (28%) of 25 patients had features of
      both types of symptoms. Lactose hydrogen breath test was abnormal in 9 cases
      (82%) of 11 diarrhoeal type of IBS which was significantly higher (p < 0.02) than
      controls. However, the difference of abnormal hydrogen breath test between
      spastic type of IBS and patients with features of both types was not significant
      as compared to controls. CONCLUSIONS: These results suggest that patients with
      diarrhoeal type of IBS have a higher incidence of lactose intolerance as compared
      to spastic type as well as patients with features of both types.

PMID- 11963326
TI  - Role of duodenal bile crystal analysis in idiopathic pancreatitis.
AB  - BACKGROUND/AIM: The aim of this study was to find out the incidence and clinical
      use of duodenal bile crystal analysis in patients presenting with idiopathic
      pancreatitis. MATERIALS AND METHODS: Sixty consecutive patients with acute
      pancreatitis were studied. They were divided into two subgroups (known and
      unknown causes). Sixty patients were used as controls and divided into 3
      subgroups (n = 20 each). The patients of acute pancreatitis with severe or life
      threatening complications or those requiring surgical interventions were
      excluded. Bile samples from both groups were analyzed for presence or absence of
      crystals. RESULTS: The maximum age incidence of acute pancreatitis was in the
      fifth decade (41-50 years). The M/F ratio was 3.6:1. Recurrent acute pancreatitis
      was observed in 26.6% cases (20% idiopathic vs. 6.6% known aetiology). Twenty
      five percent of the control sub group (n = 20) cases of cholelithiasis without
      history of pancreatitis had positive microcrystals in their bile sample. In
      patients with idiopathic pancreatitis (n = 18), 7 cases (11.6%) had crystals in
      the bile. In those with known causes of pancreatitis (n = 42), 33 cases (55%) had
      positive crystals in the bile. CONCLUSION: Thirty percent of our patients had
      idiopathic acute pancreatitis with a high rate of clinical recurrence (20%).
      Duodenal bile crystal analysis detected 7 cases of microlithiasis out of 18 cases
      in this group and suggested an aetiology. This procedure should be used more
      often.

PMID- 11963327
TI  - Soybean trypsin inhibitor confers protection against rotavirus infection in
      infant mice.
AB  - OBJECTIVE: To study the effects of soybean trypsin inhibitor (TI) on glycine
      uptake, glutathione (GSH) levels and morphological changes of intestine in
      rotavirus (RV) infected infant mice. METHODS: A total of 144 infant mice (7/8
      days old) were divided in 3 groups (i.e. control, RV and RV + inhibitor). Infant
      mice were orally inoculated with the EB strain of RV and Trypsin protease
      inhibitor (TI) and 8 animals each were sacrificed on days 0,1,3,5,7 and 10 post
      infection (p.i). Glycine uptake (in vitro), GSH levels and histological changes
      were assessed in the jejunum, ileum and colon. RESULTS: Glycine uptake and GSH
      levels were significantly reduced on days 3 and 5 p.i in jejunum and ileum of RV
      inoculated animals, compared to the controls. Glycine uptake and GSH levels were
      maintained as in controls in the RV + TI inoculated animals on days 3 and 5 p.i
      in jejunum and colon but not in ileum where lesser values were recorded.
      Histology showed vacuolar degeneration in ileum towards the apical portion
      whereas normal morphology was observed in jejunum, similar to controls. No
      histological changes were observed in colon in any of the groups. Electron
      microscopic study confirmed the viral infection. CONCLUSION: Administration of
      Trypsin protease inhibitor along with RV reverted the effects of RV infection on
      amino acid uptake and GSH levels completely in the jejunum and partially in the
      ileum.

PMID- 11963328
TI  - Pseudoaneurysm of gastroduodenal artery associated with mitral valve prolapse
      presenting as haemobilia.
AB  - Pseudoaneurysms of the hepatic or gastroduodenal arteries may cause Haemobilia.
      Mitral valve prolapse associated with mycotic pseudoaneurysm of cerebral and
      extracerebral arteries have been reported. We report a case of gastroduodenal
      artery pseudoaneurysm presenting as haemobilia. The patient was successfully
      treated with indigenously fabricated steel coil embolization followed by surgery.

PMID- 11963329
TI  - Pancreatic tuberculosis: case report and review of the literature.
AB  - Tuberculosis affecting the pancreas is rare. Its occurrence may pose diagnostic
      problem in differentiating from carcinoma of the pancreas. It usually is a
      welcome pathological surprise. A case of tuberculosis affecting the pancreas is
      reported which presented as a case of obstructive jaundice. The response of the
      disease to antituberculous drugs is good.

PMID- 11963330
TI  - A rare case of dual obstruction of the colon.
AB  - The commonest cause of large bowel obstruction is colorectal malignancy. Volvulus
      of the colon is a rare cause and caecal volvulus accounts for less than 1% of all
      cases of intestinal obstruction. Reports of concurrent occurrence of obstructing
      lesions of the right and left colon are rare and anecdotal. We report a case of
      Caecal volvulus and carcinoma of the rectosigmoid in a 70-year-old lady.

PMID- 11963331
TI  - Tubercular abdominal abscess following laparoscopic cholecystectomy: case report.
AB  - As laparoscopic cholecystectomy has become one of the most commonly performed
      operations, radiologists increasingly encounter complications resulting from
      these. Late abdominal abscesses developing as a result of dropped gallstones
      albeit unusual, have been described. Abdominal wall tuberculosis following
      laparoscopy has also been reported. We report a rare case of intraabdominal and
      abdominal wall abscesses of tubercular aetiology associated with dropped stones
      following laparoscopic cholecystectomy.

PMID- 11963332
TI  - Massive dilatation of the common bile duct resembling a choledochal cyst.
AB  - We present an unusual case in which an impacted calculus at the lower end of the
      common bile duct produced massive dilatation. This resulted in a confusing
      picture of choledochal cyst on abdominal ultrasound and endoscopic retrograde
      pancreatography. The common bile duct returned to normal size after removal of
      the stone.

PMID- 11963333
TI  - Diagnosis of gastrojejunocolic fistula by chromo-colonoscopy.
AB  - The role of colonoscopy has not been adequately evaluated in the diagnosis of
      gastrojejunocolic fistula. We report the findings and complications of routine
      colonoscopy in four patients and a novel technique 'Chromo-colonoscopy' in the
      diagnosis of this entity.

PMID- 11963334
TI  - Indicators for surgery in adhesive bowel obstruction.
AB  - INTRODUCTION: There is lack of data on risk factors, which, if present, would
      indicate the need for surgery in patients with adhesive bowel obstruction.
      METHODS: A Cohort of 100 consecutive patients with adhesive obstruction was
      studied prospectively to compare clinical and investigative parameters between
      the operative and conservative group. RESULTS: It was found that female gender,
      previous obstetric or gynaecological procedures, pulse and BP on admission,
      nature of nasogastric aspirate, single distended loop on abdominal x-ray as also
      predominant ileal distension were independent factors indicating a high
      probability of surgical intervention. CONCLUSION: Patients with 2 or more risk
      factors had 12 times higher probability of surgery and in those with 3 or more
      the relative risk was 30 times. Patients with such risk factors should be
      monitored closely after admission and should be taken for surgery after an
      initial short trial of conservative measures.

PMID- 11963335
TI  - Value of serum CEA and AFP in the diagnosis and prognosis of carcinoma
      gallbladder.
AB  - BACKGROUND/OBJECTIVE: The poor prognosis of carcinoma of the gallbladder (CAGB)
      is attributable to delayed presentation in the absence of specific clinical
      findings in the early stages. To ascertain whether the commonly available serum
      tumour markers (carcino-embryonic antigen-CEA and alpha foeto protein-AFP) could
      be used for distinguishing CAGB from other biliary disorders and in assessing the
      prognosis of patients with CAGB, serum levels of these markers in patients with
      CAGB and those with cholelithiasis were studied. METHODS: Estimation of serum CEA
      in 28 patients with CAGB and 30 patients with cholelithiasis and AFP in some of
      these cases was done by enzyme immunoassay. RESULTS: The mean values of CEA and
      AFP were 15.1 ng/ml and 166.5 ng/ml respectively for the CAGB group and 12.6
      ng/ml and 166.5 ng/ml respectively for the cholelithiasis group. There was no
      statistical difference between the groups (p > 0.05). These markers did not show
      any statistically significant correlation with the stage of disease or length of
      survival in the patients with CAGB. CONCLUSION: Serum levels of CEA and AFP do
      not have any diagnostic or prognostic significance in the management of CAGB.

PMID- 11963336
TI  - Emergency inferior mesenteric vein to left renal vein shunt in variceal bleeding:
      an alternative technique.
AB  - Shunt procedures being used in the emergency surgical management of variceal
      bleeding include total (portocaval shunt-PCS), partial (mesocaval H graft shunt
      MCS) or selective shunts (distal splenorenal shunt-DSRS). We report the use of
      inferior mesenteric vein to left renal vein (IMV to LRV) shunt in an emergency
      situation in a 24 year old patient with noncirrhotic portal hypertension with
      variceal bleeding.

PMID- 11963337
TI  - Mercedes-Benz pyloroplasty: a new technique.
AB  - Closure of large duodeno-pyloro-gastrotomy can be difficult. The resulting
      'pyloroplasty' may lead to major deformity at the gastric outlet. We describe a
      technique that combines features of the Heineke-Mikulicz pyloroplasty and V-Y
      plasty. The technique is simple and is not associated with any new post-operative
      problem.

PMID- 11963338
TI  - Gallbladder carcinoma: a disease of the Indo-gangetic belt.

PMID- 11963339
TI  - [Baker and Itagliata's Quality of Life Scale in a group of 139 schizophrenic
      patients: factorial analysis and evaluation of global validity].
AB  - The Satisfaction with Life Domains Scale SLDS published by Baker and Intagliata
      in 1982 and translated in French by Chambon and al. is one of the most used
      rating scales in the field of Subjective Quality of Life (SQL) for patients
      suffering from schizophrenia. It comprises 16 scales in 7 points and Likert
      format exploring the following fields: home/apartment/place of residence,
      neighbourhood, food, clothes, health, people they live with, friends, love life,
      relationships with their family, how they get on with other people, job/work day
      programming, spare time, what they do in the community for fun, services and
      facilities in their area, economic situation, general quality of life. In this
      study we present results on SLDS about 139 schizophrenic patients (108 males, 31
      females) recruited in two centers Lyon (n = 41) and Saint-Etienne (n = 98). The
      SLDS was a part of more comprehensive studies including evaluation of needs for
      care, social support, delivery and costs of services. Diagnosis were confirmed
      using either the SCAN and CATEGO program (n = 108) or the list of the ICD-10
      criteria (n = 31) applied at time of inclusion or on the basis of a
      representative episode of the illness. Patients were classified in two groups,
      the S group (S, n = 53) for those patients presenting clinical features at time
      of inclusion excepted residual forms (F 20.5) and the non S group (N-S, n = 86)
      for those patients free of symptoms at the time of assessment. Non parametric
      statistics (U test and Kendall test) were used for comparisons between groups.
      The field by field comparison of the scores shows the poorest level of SQL for
      love life (m = 4.2; sd = 1.8) and economic status (m = 4.4; sd = 1.8).
      Comparisons between S and non-S groups show an average range systematically
      higher for the non-S group and significant differences for the following fields:
      food, friends, how they get on with other people. The same comparisons between
      males and females show no significant differences excepted for the following
      fields: love life, economic situation. Principal components analysis with Varimax
      rotation were performed and a 4 factors solution was considered as the best one.
      Before rotation the first factor accounts for 31% of the variance and comprises
      all the items with loading higher than 0.4 allowing us to consider the
      possibility of a global score. This global score is normally distributed (m =
      95.1 sd = 17.3) and shows a significant difference between S and non S-groups (S
      m = 92.2 sd = 20.1; non S m = 99.6 sd = 15.4 p = .02) but not between centers and
      between males and females. After rotation the first factor comprises
      relationships with family, how they get on with other people, job/work/day
      programming, spare time, what they do for fun and life in general. The hypothesis
      of unidimensionality of QV has to be tested using the RASCH model.

PMID- 11963340
TI  - [Bipolar obsessive-compulsive disorder: confirmation of results of the "ABC-OCD"
      survey in 2 populations of patient members versus non-members of an association].
AB  - Clinical data are largely focused on depressive comorbidity in OCD. However in
      practice, treating resistant or severe OCD sufferers revealed many cases who seem
      to have an authentic OCD with a hidden comorbid bipolar disorder. Most reports
      had evaluated the OCD comorbidity in unipolar and bipolar mood disorders (Kruger
      et al., 1995; Chen et Dilsaver, 1995). The only investigation in clinical
      population focused on the reverse issue was conducted in Pisa. Perugi et al.
      (1997) have showed in a consecutive series of 315 OCD outpatients, that 15.7%
      presented a bipolar comorbidity, mostly with BP-II disorder. Further analyses
      suggested that when comorbidity occurs with bipolar and unipolar depression, it
      has a differential impact on the clinical picture and course of OCD. The rate of
      bipolar comorbidity in OCD was analyzed in a recent epidemiological survey
      undertaken by the French Association of patients suffering from OCD (FA-OCD or
      AFTOC in French). In a sample of 453 OCD patients, 76% had suffered from a major
      depression, 11% from bipolar disorder (DSM IV mania or hypomania), 30% from
      hypomania (cases that obtained a score > or = 10 on the self-rated Angst
      Hypomania Checklist). According to the score > or = 10 on Self-rated
      Questionnaire for Cyclothymic Temperament, 50% were classified as cyclothymic.
      The self-assessment of soft-bipolar dimensions, such as hypomania and cyclothymia
      was previously validated in a multi-site study in major depression (Hantouche et
      al., 1998). Further analyses showed that comorbidity with soft bipolarity was
      characterized by significant interactions with high levels of impulsivity, anger
      attacks and suicidal behavior. In order to confirm these data, another cohort (n
      = 175 patients treated by psychiatrists for OCD) was formed and named "PSY-OCD".
      Comparative analyses between the two populations allowed showing very few
      demographic and clinical differences. The frequency rate of "bipolar OCD" was
      equivalent in both populations: BP-II disorder (DSM IV criteria) was present in
      11% of FA-OCD and 16% of PSY-OCD. Furthermore using the Hypomania Checklist
      showed that BP-II disorder rate (score > or = 10) was higher: 32% of in both
      populations. Cyclothymic rate was also globally higher, but significant
      difference was obtained: 56% of FA-OCD versus 45% of PSY-OCD (p = 0.02).
      Moreover, mood switching rate under anti-OCD drugs was equivalent in both OCD
      populations (respectively 38% and 33%, p = ns). In case of BP comorbidity,
      patients had presented a greater number of concurrent major depressive episodes
      and suicidal attempts. When concurrent depression was considered, the rate
      diagnosis of soft bipolarity was 2.5 fold, and the number of suicidal attempts
      augmented by 7 fold (by comparison versus non-depressed OCD). Despite very early
      descriptions (since the beginning of the last century) of particular
      relationships between so-called "psychasthenia, folie de doute, folie
      raisonnante" and "circular and intermittent madness or cyclothymia", a few
      attention has been devoted to this complex pattern of comorbidity. The
      comparative data deriving from the collaborative survey with patients who are
      members of AFTOC and with a cohort of psychiatric outpatients, confirm the
      reality of bipolar-OCD comorbidity, which is largely under-recognized in clinical
      practice. More in depth analyses are now undertaken in order to investigate the
      characteristics of "bipolar OCD" by comparison to "non bipolar OCD".

PMID- 11963341
TI  - [Suicidal Risk Scale].
AB  - Assessment of para-suicidal patients is one of the main tasks for the
      practitioner in an emergency unit. There are now any characteristics known as
      suicide risk factors, like drug or alcohol abuse, past history of suicides in the
      family, or psychiatric disorder. However though these characteristics are useful
      to define high-risk populations, they are not always relevant in personal
      assessment. The more relevant variables in this case are psychological.
      Unfortunately, there are very few assessment scales in this area, since scales
      are usually related to the prediction of suicide or para-suicide before the act.
      The only existing tool for assessment after the act is the Beck Suicidal Intent
      Scale (SIS, 1974), which assesses the wish to die. Therefore we propose a new
      scale for a global assessment of parasuicide: it is an eleven-items scale,
      divided in four sections. Each section assesses: (1) the parasuicide itself, with
      the wish to die, the way to die and precautions against intervention; (2) the
      patient himself, with the premeditation level, an affective disorder existing
      before the act, the means of future, and environment effect (in a sense of
      protection or risk); (3) the global impression after the psychiatric interview:
      the emotionalism level, and the trust in the patient attitude; (4) the patient
      history: alcohol or drug abuse, personal past-parasuicide. The scale construction
      was empirical, from clinical practice, but it encompasses the nine high-risk
      variables found by Motto and Bostrom (1990) in an analysis of prospective data
      from 3,005 psychiatric patients at risk for suicide, focusing on 38 persons who
      committed suicide within 60 days of evaluation. Our study has been conducted on a
      77 sample of para-suicidal patients in the psychiatrist emergency unit of the
      Avignon Hospital. For each patient, the score from our scale was calculated by
      psychiatric nurses after their own interview, before psychiatric examination,
      about 12 or 24 hours after the entrance in the emergency unit. Then, patients
      were classified in four groups according to the psychiatrist decision and
      orientation: exit (n = 7), consultation (n = 34), hospitalization (n = 24),
      hospitalization under constraint (n = 12). These groups mean theoretically an
      increasing global gravity: it is possible for example to hospitalize a
      parasuicidal patient because he wants to die, even without depression. Or in an
      other case, if he has a very serious psychiatric disorder (for example affective
      or psychotic), with a low-lethality para-suicide. Moreover, for a 22 sub-sample
      patients, the score from Beck-SIS was also calculated. The scale scores
      comparison in the four groups were made by analysis of variance: there was a
      statistically significant difference between groups as whole and individually (p
      < 0.001). In the second analysis, we defined two subsamples: the first one
      contains the hospitalized patients (n = 36) and the second one, the non
      hospitalized (n = 41) patients. Statistically, from the scale scores, it was
      possible to define a threshold above which all the patients were hospitalized,
      and an other one under which all patients were not hospitalized. Third, there was
      a good correlation between lethality scores in our scale (first section) and the
      Beck SIS scores (r = 0.91). In conclusion, our scale seems to be well correlated
      with global gravity meant by parasuicide, to assess correctly suicidal intent,
      and to provide reliable indicators for hospitalization. However, some aspects are
      still missing in this study: we did not compare any sub-score with other well
      known scales, assessing depression or hopelessness. On the other hand, we
      couldn't obtain prospective data on all the patients after their parasuicide. The
      following steps will be to carry on with these studies, as well as with the
      replication of our results on larger samples.

PMID- 11963342
TI  - [Characteristics of patients hospitalized in a specialized hospital center after
      after attempted suicide].
AB  - Authors have counted, during a period of one year, the totality of patients
      having been admitted to the Centre Hospitalier Specialise de la Savoie (Chambery)
      following a volunteer medicinal intoxication; 227 patients have been thus
      included, this type of acting out concerning third more women than men. The
      higher impact is found in young adults (20-40 years). Professional inactivity
      appears as a favoring factor, while the way of life (bachelor or in couple) does
      not seem to have consequence on the frequency of occurrence of the suicidal
      attempts. Relapses are numerous, and happen in most cases during the year.
      Concerning used medicines, they have been generally prescribed by a practitioner
      or a psychiatrist. The prominent fact is the presence of a very short period
      between the prescription, the deliverance of the medicine and the acting out.
      Plurimedicinal intoxications are increasingly frequent, with often concurrent
      absorption of alcohol. The diminution of the use of barbiturics in ambulatory
      medicine to the profit of other molecules, and especially the benzodiazepines,
      has reduced the frequency of their use in volunteers medicinal intoxications.
      Benzodiazepines are the most employed medicines in this type of acting out. This
      epidemiological and toxicological study confirms that used substances during
      volunteer medicinal intoxication are a reflection of the general medicinal
      consumption.

PMID- 11963343
TI  - [Influence of depressive history on biological parameters in major depression].
AB  - BACKGROUND: Major depressive disorder is associated with several biological
      abnormalities. Among them, sleep disturbances and alterations of hypothalamic
      structures and cortisol system have been largely studied. Most studies have found
      a relationship between depression and alteration of sleep. Electroencephalic
      sleep profiles during depression demonstrate abnormalities of sleep continuity,
      reduction of slow waves sleep and REM pressure (27). The cortisol system,
      investigated by the Dexamethasone Suppression Test (DST), is abnormal in about an
      half of the depressed subjects. We confirm a cortisol escape from suppression by
      dexamethasone (21). A complex dysregulation of the Hypothalamic Pituitary Adrenal
      axis (HPA) is thought to explain this escape (15, 33). The HPA has been first
      involved in the theory of stress. There are two ways to study this. First by
      looking at early adversities and genetic susceptibility to stress, and second by
      studying acute stressors and depressive reactions (8). The sensitization model
      postulated that the acute abnormalities of depression may leave biological
      scares. Those scares could make people more vulnerable to latter depressive
      triggers (34). We could then suppose that biological correlates of depression
      become more severe during the course of the illness. The present study further
      examines relationships between DST, polysomnography and some clinical and
      epidemiological characteristics of the depressive illness. We tried to examine if
      there were increasing biological disturbances during the course of the illness.
      We also examined the effect of the history of illness on the psychosocial
      stressors, and the effects of those stressors on the biological correlates of
      depression. METHODS: The DST and polysomnographic recordings were performed in a
      sample of 130 inpatients with primary major depressive disorder, unipolar form,
      as defined with the RDC (41). All of those patients have been consecutively
      admitted to the Sleep Laboratory of the Department of Psychiatry, Erasme
      Hospital, between 1981 and 1992. This population has been previously reported
      elsewhere (19, 20, 21). The depressive symptom severity was assessed with the 24
      items HRSD (17). The Newcastle Endogenous Depression Diagnostic Index was used to
      assess the endogenous character of the depressive episode (5). The history of the
      illness and the impact of psychosocial stressors were assessed retrospectively
      using the interview associated with the RDC (41), the SADS (7). Psychosocial
      stressor has been assessed using the item 216 of the SADS. We must remind that it
      is not a precise measurement of stress. RESULTS: Table I shows clinical
      characteristics and biological variables in our 130 depressed patients. No
      correlation were found between number of depressive episodes and DST or EEG sleep
      records (table II). Age of onset was correlated with DST and all sleep EEG
      parameters (REM latency, REM density, awakening and slow wave sleep). But the age
      was a major confounding factor. When corrected the results for age, a significant
      correlation between age of onset and DST still remained, but no correlation
      between age of onset and EEG sleep results (table III). The psychosocial
      stressors were correlated only with awakening. A positive trend was found between
      an augmentation of psychosocial stressors and the number of episodes (p = 0.06).
      CONCLUSION: This study does not support the view that the biological correlates
      of depression are worsening with the course of the illness. We found only
      correlation between age of onset and DST, but a possible confounding effect of
      age cannot formerly be excluded. The impact of psychosocial stressors on the
      biological correlates of depression was minimal. The only significant correlation
      found was between awakening and psychosocial stressors. We found no correlation
      between psychosocial stressors and the course of depression. Those results do not
      support the view of sensitization of the illness, but it should be remember that
      evaluation of psychosocial stressors by item 216 of the SADS was probably not a
      sufficient sensitive measure. We suggest thus that the impact of the history of
      depression on biological correlates of depression is not very strong. An
      alternative explanation of the lack of correlation found is that we used
      inaccurate measurement of the course of depression. For example, we had no
      evaluation of the quality of remission between different episodes of depression
      and of subsyndromic depression. Recent works show the importance of this (6, 9).
      The major limitations of this work were the retrospective character of the study
      and the low precision of the evaluation of psychosocial stressors used.

PMID- 11963344
TI  - [Was Snow White a transsexual?].
AB  - The Rorschach Ink Blot test is considered to be an essential analytical
      instrument when studying the personalities of individuals presenting identity
      disorders, in particular, in the context of a sex change request. Nevertheless,
      there exist less than 20 studies of transsexualism utilising the Rorschach since
      the creation of this diagnostic category in 1953. This research has mostly
      concerned itself with relations between psychopathology and transsexualism.
      Practically non-existent are studies investigating the psychological conditions
      that permit, shape or induce sex change requests in individuals. Transsexuals
      request the removal of their genitals through mutilation surgery, which can be
      seen as subjects literally crying out to be castrated. This request is all the
      more surprising given that castration, in psychoanalytic terms, is considered to
      be the most severe punishment that an individual (woman or man) can be threatened
      with. Therefore, we asked ourselves which psychic conditions could motivate such
      as request. Based on any earlier study where answers (some explicit, others
      symbolic) given by sex-change applicants tested on the Rorschach were analysed,
      results seemed to suggest a counter-phobic attitude underlying sex-reassignment
      requests (28). According to these hypotheses, the fear of castration (banal as
      such) can only be overcome through the active search for castration itself. In
      opting for castration, the transsexual puts an end to the states of anxious
      waiting that are dominated by feelings of the incertitude and unpredictability of
      an eventual castration. Once obtained, the threat it constituted disappears, and
      with it so does the fear. Thus, by taking this active and voluntary step, the
      subject is no longer exposed to an imminent danger in a passive manner. This in
      itself creates a great feeling of relief, if not of actual pleasure in the
      subject (28). In this article, we postulated in a purely speculative manner, the
      existence of one or several modalities in the transsexual dynamics. Nevertheless,
      one can ask oneself about the possibility of a request based on a desire rather
      than on a defense, or even on the existence of a defensive process diametrically
      opposed to the counter-phobic attitude and which, instead of actively provoking
      the dreaded reality, would privilege its avoidance and the search of passivity.
      This latter hypothesis has the advantage of being rather easy to explore with the
      Rorschach because, according to Exner, the predominance of passive compared to
      active human movement responses (which he terms the Snow White Syndrome)
      indicates the propensity to escape into passive fantasies and the tendency to
      avoid the initiative for behaviour or decision-making, if other people can do it
      in the subject's place (12). Our results largely confirmed the hypothesis of the
      existence of an opposite mechanism, as a third of subjects (n = 26) presented
      Snow White Syndrome. According to Exner, these transsexuals are typically
      characterized by hiding into a world of make believe, avoiding all
      responsibility, as well as any decision-making. This passivity in our Snow White
      Syndrome group was all the more remarkable in that, on the whole, it infiltrated
      into all the movement responses and seemed to define a rigid style of thinking
      and mental elaboration, in addition to a suggestive content of passivity.
      However, this condition cannot be associated with a general lack of dynamism or
      energy. In fact, the treatment of information, which provides data concerning the
      motivation to treat a stimulus field of the stimulus--whether this concerns the
      capture (L) of the stimulus or the elaboration (DQ+) of the response--displayed a
      sufficient amount of motivation. Furthermore, internal resources (EA) were
      considerable and were brought into play whenever it was necessary to adopt a
      behaviour or make a decision. Furthermore, based on these Rorschach findings, we
      note that in transsexuals with Snow White Syndrome, there is a stereotyped
      tendency to shy away from difficulties by seeking refuge in realistic
      representations (but that lack in variety), which could be materialized by
      actions, but where the initiative is delegated to others. These transsexuals
      appear to shy away from the difficulties of life by seeking refuge into a world
      of fantasy, which they fill with the representations borrowed from reality
      (rather than fantasy) and consequently that are liable to be transposed, if
      necessary, back into reality. Therefore, one can better understand why they shun
      away from the deceiving reality that their physical sex represents, into the
      satisfying dream where they possess the genitals of the opposite sex, that is, a
      perfectly real organ, no longer the result of the subject's fantasy world.

PMID- 11963345
TI  - [Detection, prevention and treatment of postpartum depression: a controlled study
      of 859 patients].
AB  - This study evaluated the clinical effectiveness of a programme aimed at
      detecting, preventing and treating postpartum depression. The French version of
      the EPDS was used to measure the intensity of postpartum blues on a sample of 859
      women, during their stay at the obstetrical clinic. Subjects under treatment for
      psychological problems were excluded from the study. Mothers scoring 9 or above
      on the EPDS, which is predictive of pospartum depression, were randomly assigned
      to a prevention and a control group. Written informed consent was obtained from
      the subjects after the study procedure had been explained. The prevention group
      received a counselling session integrating supportive, educational and cognitive
      behavioral components. Therapists included five female Master's Degree level
      students in psychology. All therapists participated in didactic and clinical
      training as wells as weekly supervision from the first author. All subjects were
      given a second EPDS with written instructions to complete the questionnaire
      during the period 4 to 6 weeks postpartum and return it for analysis. At four to
      6 weeks, women in the prevention group had significant reductions in the
      frequency of probable depression, as defined by a score of 11 or above on the
      EPDS (30.2% vs 48.2%, chi 2 = 7.36, dl = 1, p = 0.0067) and in the intensity of
      depressive symptoms measured by the mean score on the EPDS (8.5, SD = 4 vs 10.3,
      SD = 4.4, t = 3.06, dl = 209, p = 0.0024). Mothers with a probable depression
      were interviewed at home and assessed using the MINI (Mini Neuropsychiatric
      Interview, Lecrubier et al., 1997) to diagnose major depressive episode, the SIGH
      D (Structured Interview Guide for the Hamilton Depression Rating Scale, Williams,
      1988) and the BDI (Beck Depression Inventory, Beck et al., 1988). The baseline
      depression rating scores, EPDS (mean = 13.6, SD = 4), BDI (mean = 15.7, SD =
      5.9), HDRS (mean = 14.8, SD = 6), were consistent with moderate depression. No
      significant differences in baseline scores were observed between the two groups
      on all the rating scales (p < 0.001). Mothers with probable depression in the
      prevention group were offered a program of 5 to 8 home visits. Most of the
      mothers in the prevention group (72%) agreed to participate in the program. On
      the contrary, most of the mothers (83.3%) who scored below 9 on the first EPDS
      and 11 or above on the second, who so did not received the preventive counselling
      session, declined to participate. This suggests the importance of the preventive
      session in establishing therapeutic alliance. The home visits program integrated
      four components, supportive, educational, cognitive-behavioral and psychodynamic
      centred on the mother-infant relationship in terms of the mother's personal
      history. Therapist participated in clinical training and weekly supervision.
      Fifteen women (71.4%) in the study group demonstrated complete symptom remission,
      as defined by HDRS score below 7 after the intervention, compared with 4 women
      (10.5%) in the control group (chi 2 = 23, p < 0.0001). A clearly therapeutic
      response to treatment was observed in the treated group with a mean reduction in
      HDRS score of 9.5 (DS = 6.7) from baseline. The improvement in the women in the
      treated group, as measured by the mean HDRS scores was statistically greater than
      that in the control group (m = 5.35, SD = 3.5 vs m = 15.8, SD = 4.6, t = 8.24, dl
      = 52, p < 0.0001). Our results indicate that a program based on an intervention
      at obstetrical clinics and on home visits is efficacious and well accepted for
      prevention, detection and treatment of postpartum depression.

PMID- 11963346
TI  - [Value of a consultation center and crisis intervention in addressing psychiatric
      disorders in the perinatal period].
AB  - The Psychiatry department of the University Hospital Centre of Lille has
      developed, over the last 10 years, a treatment network for psychiatric disorders
      during pregnancy or in the post-partum period. There are liaison consultations in
      the maternity department, screening and management of psychopathological
      disorders in the perinatal period, training of midwives, support of patients
      seeking genetic counselling, collaboration with teams providing "medically
      assisted procreation", etc. For severe disorders of the post-partum period
      (severe depression, serious alteration of mother-child interaction, puerperal
      psychosis), the Psychiatry department has a specialized unit where 3 "mother
      child" groups can be admitted. This unit is particularly effective if the
      patients and their family understand this healthcare system and stick to it to a
      certain extent. Even if improvements are always possible, cases in which
      situations occur as an emergency, are when dysfunctions are most frequently seen.
      On 7th December 1998, a Crisis Intervention Unit (CIU) was created with 15 short
      term beds, for stays up to 72 hours. The CIU was opened in the Psychiatry
      department, close to the main Accident and Emergency department, with 2 aims:
      firstly to provide a setting and resources for a number of emergency psychiatric
      situations, and secondly to provide a place and time for crisis situations which
      we admit to the unit, with a view to facilitating interaction and to propose in
      certain cases a process of crisis intervention, which later continues on an
      outpatient basis. After being open for a year, the CIU has proved to be an
      improvement to all of the healthcare services which are available. It should be
      noted that the situations which need highly specialized resources in such a short
      time, are those which cause the most acute problems. This is at times when the
      emergency services network, with its internal logic, require another network
      based on a different logic, that the interface problems are at their most acute.
      The situations reported here, which require a fluid interface between the
      emergency services and the "mother-child" networks, are examples. We report 3
      clinical situations, which illustrate 3 possibilities of action: the first, in
      which 2 successive stays in the CIU allowed an admission to the "mother-child"
      unit in satisfactory conditions, the second, in which overall management was
      based on hospitalization in the Obstetrics department and several visits to our
      Unit, and the last one, in which the whole medico-psycho-social approach was set
      up after a single stay of 3 days. Since the opening of Crisis Intervention Unit,
      around 1,000 patients have been treated there; 37 were women with difficulties
      with their pregnancy, 17 of whom required direct intervention by the "mother
      child" team. The contexts were: 5 prenatal depressions, 4 post-partum
      depressions, 3 cases of hyperemesis gravidarum, 5 rejections of pregnancy and/or
      situations at risk of infanticide. The almost constant suicidal risk should be
      noted, or even attempted suicide, at the time of admission to the CIU. The other
      20 women had psychopathological disorders linked to sterility, medically-assisted
      pregnancy, termination of pregnancy or pregnancy in women suffering from long
      term somatic illnesses (insulin-dependent diabetes, lupus, etc.). When a
      psychopathological episode occurs during pregnancy, it is essential to preserve
      the developing relationship with the child in an intermediate place, in a
      healthcare perspective and to prevent any future impairment of the quality of the
      mother-child relationship by the psychiatric disorder. The Crisis Intervention
      Unit is not an emergency "mother-child" unit. Other French experiences have been
      reported, an example being mother-baby hospitalization in a crisis centre. The
      aim of our interventions is not the same, and our local context, together with
      the availability of a healthcare network on different floors, which is specific
      and close-by, allows this approach. Also, the contribution of Liaison Psychiatry
      in emergency situations should not be minimized. It is necessary to work in
      collaboration with the obstetricians. In fact, the chance to work with us was
      given by asking for a hospitalization in the Obstetric unit, during the prepartum
      period of pregnancies with a psychiatric risk. This way of proceeding allows
      somatic monitoring in hospital to be performed, whenever the risk run by the
      mother and/or the child requires it. This "analogue" procedure, however
      preventative it may be, does not always allow specific treatment of the
      psychiatric disorders to be given, despite liaison psychiatry interventions. Our
      interventions are not a specialized "mother-child" unit, or a substitute for
      Liaison Psychiatry, but they are specifically aimed at the context of the crisis.
      Obviously, it is precisely this dimension of the crisis which makes the other
      types of management temporarily unsuitable. This new working framework, with the
      simple possibility of admitting women and interacting with them in a crisis
      situation, with the aid of the competence of "mother-child" teams, most often
      seems to allow an alternative to hospitalization in the Psychiatry department, at
      the same time keeping up quality management of problems linked to the pregnancy
      or post-partum period. The specificity of the CIU, with its project of taking the
      special psychiatric vulnerability of pregnancy into account, makes sure that the
      psychopathological aspects of the crisis situation and the physiological aspects
      of adaptation reactions to the perinatal period are not neglected, but that are
      respected by this type of interaction/intervention.

PMID- 11963347
TI  - [Cannabis-related flash-back, a medico-legal case].
AB  - Cannabis is a psychoactive drug more and more widely consumed in industrialized
      countries and in the world. Amongst the numerous effects it can induce, flashback
      phenomena have been scientifically recognized only since the 70's. This case
      regards a young man who offended a friend without any objective reason. The
      report of the forensic psychiatrist demonstrated that the offense was committed
      under the influence of a cannabis flashback. The last time the offender had
      consummed cannabis, probably from Netherland, was two weeks before the acts. A
      plasmatic detection was realized and showed a level at 6 ng/mL, thirty minutes
      after the beginning of the flashback. This case confirms the clinical entity of
      cannabis flashback and gives an exceptional indication on THC blood concentration
      at the time of the relapse. But the pharmacokinetics of the phenomenon are
      largely unknown and long term studies concerning the metabolism, not only of THC
      but also of its metabolites, are needful. On the forensic standpoint, the
      possible participation of flashback phenomena must not be neglected when grounds
      of unexplained accidents or crimes are searched.

PMID- 11963348
TI  - [Naturalizing empathy].
AB  - Empathy is the ability to share emotions with others. It is acknowledged to be a
      powerful means of tacit communication, a key ingredient in any therapeutic
      relationship as well as in psychotherapy. Empathy is the cornerstone in the
      humanist perspective (Ego-psychology) in clinical psychology. This approach is
      often considered as poorly grounded on scientific and objective evidence. It is
      however acknowledged that empathetic therapists are more effective than less
      empathetic therapists. I shall argue that this paradox, i.e. it is the least
      scientific and the less validated psychotherapeutic approach that is the most
      efficient, can be eliminated if one considers the nature of empathy, its
      biological foundation, its evolutionary origin and its cognitive architecture. In
      this paper I will suggest that empathy is based on specific information
      processing modules which have been designed by natural selection to cope with
      social regularities in expressing and reading emotional states. This has provided
      adaptive benefits to individuals living in large groups bestowing them with
      mechanisms for cooperativity, altruism and more generally various aspects of
      prosocial behaviour. The capacity to express emotions, and to read and understand
      emotions of others also ensures implicit communication with others and may be at
      the root of intersubjectivity. This perspective on empathy is then articulated
      with two concurrent hypotheses regarding theory of mind (the simulation and the
      theory-theory) which aim to explain the human capacity to understand that the
      behaviors of other intelligent agents are caused by intentions, desires and
      beliefs. In this context, empathy can be considered as a simulation (or
      analogical) process that is necessary to understand but not sufficient to
      interpret other people. This last issue is relevant to clinical practice.

PMID- 11963349
TI  - Diazepam use during pregnancy: a review of the literature.
AB  - Antianxiety medications such as benzodiazepines (BZDs) are frequently and
      appropriately used to ameliorate the anxiety symptoms of depression, dysthymic
      disorder, panic disorder, agoraphobia, obsessive-compulsive disorder, generalized
      anxiety disorder, eating disorder, and many personality disorders. Pregnancy may
      be accompanied by anxiety necessitating therapeutic intervention by anxiolytic
      drugs like BZD. Keeping in view the potential risks of teratogenicity and direct
      neonatal toxicity, BZDs with established safety records should be used, while
      avoiding exposure in the first trimester, especially with multidrug regimens, and
      prescribing the lowest dose for the shortest duration. This literature review
      highlights information from various sources regarding safety data of exposure of
      pregnant and lactating mothers to long-acting BZDs, especially diazepam.

PMID- 11963350
TI  - Medical records, patient lists, trade secrets, duties to patients, and non
      competition among Delaware physicians.

PMID- 11963351
TI  - Physicians urged to recommend Pap tests to women ages 65 and older--new
      educational materials now available from NCI.

PMID- 11963352
TI  - Medicare prevention: moving toward research-based policy.

PMID- 11963353
TI  - Caring for an aging society: cohort values and eldercare services.
AB  - Understanding the impact of cohort values is important in trying to project
      future aging service needs. The cultural characteristics of cohorts yet to reach
      the age of 65 are compared with those already "old," with specific focus on the
      Baby Boomers. Aging policies (and available services) reflect the cultural
      notions of age and aging held as normative during the historical era in which
      they are enacted. Previous research into lifestyle preferences, consumer
      practices, and key characteristics is drawn upon to investigate the values of
      Baby Boomers in light of their projected needs for eldercare services. Cohort
      research and generational marketing practices offer a promising foundation for
      exploring how best to develop, target, and deliver aging services that most
      effectively utilize our social resources.

PMID- 11963354
TI  - Vertical axes on the long-term care continuum: a comparison of board and care and
      assisted living.
AB  - As the continuum of long-term care has expanded, public funding has not
      accompanied new care options. I detail access, provider profits and resources,
      and care quality in two types of residential care that fall in the center of the
      continuum, assisted living and board and care. These two options provide examples
      of how limited public funding leads to vertical axes, which represent access to
      services, the resources providers draw on to give care, and the quality of long
      term care services, at each service point on the long-term care continuum.

PMID- 11963355
TI  - Managed care for Medicare: some considerations in designing effective information
      provision programs.
AB  - Consumer information-processing theory provides a useful framework for policy
      makers concerned with regulating information provided by managed care
      organizations. The assumption that consumers are rational information processors
      and providing more information is better is questioned in this paper. Consumer
      research demonstrates that when faced with an uncertain decision, consumers adopt
      simplifying strategies leading to sub-optimal choices. A discussion on how
      consumers process risk information and the effects of various informational
      formats on decision outcomes is provided. Categorization theory is used to
      propose guidelines with regard to providing effective information to consumers
      choosing among competing managed care plans. Public policy implications borne out
      of consumer information-processing theory conclude the article.

PMID- 11963356
TI  - Recent developments in the employment and retirement of older workers in Germany.
AB  - Against a background of an aging population, rising social security costs, and
      foreseeable labor and skill shortages, there have been public policy changes
      affecting older workers in Germany. Labor-market related initiatives aim at an
      increase of labor force participation among this group. Enterprise-related,
      active age-management strategies aim at improving occupational conditions of
      aging workers. In this context, prolonging the working life must be seen as one
      option of "active aging." Another view of the current retirement discussion is
      the question of how the unused potential of Germany's younger, early-retired
      seniors can be exploited. Active aging has become a social duty nowadays, with
      the intention that older persons contribute to society to avoid generational
      conflicts. In the future, active aging will preserve the competitiveness of
      enterprises and of the entire economy, despite an aging labor force. But
      gerontological research points out that different options to carry out individual
      life plans of active aging are also required. This article reviews the changes in
      public policies towards older workers and includes the findings of a project that
      illustrates good practice to combat age barriers in the labor world.

PMID- 11963357
TI  - [Primates as experimental animals].
AB  - The term "primates" comprises a varied group of animals, consisting of more than
      250 different species. The close evolutionary relationship to man resulted in the
      use of nonhuman primates as subjects of study for scientists from different
      research fields. In biomedical research the use of primates is restricted to
      questions which cannot be answered by animals with less developed physiological
      senses. Primates play an important role in infectious disease research, as many
      pathogens relevant to humans can be transferred to selected primate species. In
      the last few decades this applied especially for HIV-infections of man, viral
      hepatitides, herpesvirus infections and for quite a long time for agents of
      transmissible spongiform encephalopathies, too. In neurobiology, primates play an
      outstanding role due to the morphological-structural and functional resemblance
      of their CNS to that of man. Due to new developments in biomedicine, in
      particular in the field of gene therapeutics, it has to be expected that primates
      will have to be used also in future as animal models for the welfare of human
      health.

PMID- 11963358
TI  - [Possibilities and limits of the inspection of animal experiments and laboratory
      animal facilities].
AB  - Animal experiments according to section 7-9 of the German animal welfare act
      underlie governmental inspection. Generally this inspection is taken over by the
      veterinary offices of the cities and districts. During the inspection of animal
      experiments, which have to be licensed or announced according to section 8 or 8a
      respectively, the main focus should be the observance of the license presumptions
      and conditions, the knowledge of the experimenter and the necessity of
      recordings. For this task specialized knowledge in laboratory animal science of
      the inspection office is a necessary presupposition for the effectiveness and
      acceptance of the inspection. As this inspection can only be spot-checking it
      should be done in a close and collegial cooperation with the animal welfare
      officer of the experimental institution. The animal welfare officer has the
      necessary knowledge and knows the institutional conditions, especially the time
      scheme, which are necessary for an effective inspection of animal experiments.
      Without the participation and cooperation with the animal welfare officer the
      inspection office runs the risk not to recognize certain interrelations, but also
      to give way to wrong descriptions. It is very difficult especially during the
      inspection of institutions, where many research groups perform animal experiments
      to get and to keep an overview, without not noticing important details or
      focussing on certain details, while others are taken no notice of. The primary
      goal of the inspection of animal experiments should be: 1. to understand the
      research goal and the methods used 2. to ask with scientific background for the
      purpose of research and the experimental design 3. to judge the applied
      experimental methods in respect to animal welfare aspects 4. to improve the
      animal experimentation by discussion with the experimenter Does the inspection
      office succeed to be accepted as a competent partner by the experimenter as well
      as by the animal welfare officer, the inspection of animal experiments itself as
      well as the achievement of refinement for practical animal welfare is more easy
      and more effective than a simple bureaucratic control.

PMID- 11963359
TI  - [Injuries caused by outside violence with forensic importance in horses].
AB  - Traumatic injuries are common in horses and may be caused by self-infliction,
      accident or in an increasing number by an act of violence. Over a four year
      period, 193 horses with injuries caused by self-infliction or accident were
      referred to the clinic. In addition, ten horses with injuries associated with an
      act of violence had to be treated. Those injuries were caused by gunshots, or
      were stab wounds caused by spear like instruments or knives. Furthermore, cases
      of zoophilism and zoosadism were observed. Penetrating injuries were potentially
      life-threatening and in particular injuries with soft tissue damage extending
      over the limits of visible injury required a special approach. Of the ten horses,
      seven survived by surgical or medical treatment. Beside of medical aspects,
      forensic aspects should be considered in such cases.

PMID- 11963360
TI  - [Criminal acts against horses--phenomenology and psychosocial construct].
AB  - Since 1993 increasing numbers of violent crimes against horses were recorded in
      Germany. Meanwhile "Horse Ripping" is accepted as a new criminal phenomenon. It
      is defined as destructive acts with the aim to harm a horse or the acceptance of
      a possible injury of a horse, especially killing, maltreatment, mutilation and
      sexual abuse in sadomasochistic context. The study includes a complete situation
      report from 1993 to 2000, especially the development of the crime. Criminal
      events (N = 1035) were analysed about modus operandi, especially the
      specification of the injuries and regional distribution. The victims were
      selected of sexual differences in modus operandi and regional distribution.
      RESULTS: The perpetrators injure the horses systematically. 25% of the injuries
      are situated at the genitals and another quarter of the victims are injured at
      the neck or the head. There is a victim preference for female individuals, which
      are treated as rape. The injuries are mostly stabs or cuts. The used weapons are
      knives or spears. First interviews with horse rippers point out that the fixation
      of the victim horse is not stable. Horses could be just representative victims
      and the act of horse ripping just a step in a criminal career of violent crimes.

PMID- 11963361
TI  - [Keeping of bears and big cats in the zoo and circus].
AB  - The exhibition of bears and big cats in zoo and circus causes regular criticism,
      justified and unjustified, by people engaged in the prevention of cruelty to
      animals. Main points of critique are holding conditions, feeding and health
      status of the animals. The official veterinarian involved in the supervision
      often needs the cooperation of a specialised zoo veterinarian. In most cases the
      clinical examination of bears and big cats requires an immobilisation. This
      article will enter into some of the most common holding problems and diseases of
      big carnivores in zoo and circus.

PMID- 11963362
TI  - [Keeping of elephants in the zoo and circus].
AB  - There is a decrease in the number of elephants kept in European zoological
      gardens and circus companies. In the future the import of animals will only be
      possible for holders which are able to keep family-groups of elephants under
      species-specific conditions. This will not be possible under circus conditions.
      This article will describe some problems observed in elephant holdings in
      zoological gardens and circus companies.

PMID- 11963363
TI  - [Keeping of horses in circus and show businesses].
AB  - The conditions under which horses are kept and the performance of acts in the
      circus ring may give rise to animal protection-relevant aspects for circus and
      show horses. A number of intolerable conditions under which horses are kept and
      procedures adopted for the work with circus and show horses are described. In
      addition, attention is drawn to monitoring methods capable of exposing the
      deplorable shortcomings of these businesses.

PMID- 11963364
TI  - [Official veterinary supervision of zoos--experiences in Brandenburg].
AB  - Based on the law of animal welfare and on the EU-rule about keeping of wild
      animals in zoological gardens 15 zoological gardens in Brandenburg were inspected
      by a temporary team consisting of one veterinarian from the state office of feeds
      and agriculture, the local authorized veterinarian and one director of the
      zoogardens. Data of every zoological garden at first were recorded by special
      lists of queries. So it was possible to estimate the keeping conditions and to
      realize deficiencies and the main problems. During the local inspection these
      data were controlled and the structure of keeping units as well as the conditions
      and behaviour of the animals were evaluated. Every unit was evaluated taking into
      consideration all points of view. If necessary proposals for improvements were
      made which were to enforce by the local authority. Furthermore the documentation
      and the economic areas were inspected. The number of kept species and animals was
      relatively low. Only two zoological gardens were to classify as mean ones. The
      majority of the fences and aviaries corresponded with the minimal demands of the
      today rules resp. was larger in the dimension and space. There were very nice
      keeping units, but also some deficiently in the structure or in the quality of
      the ground. By some photographs positive and negative examples are demonstrated.
      The feeding and also the veterinary service were on high level. The team found
      out that staffs of the zoogardens had a positive position to animal welfare. Step
      by step they improved the keeping conditions. The central inspection by a multi
      professional team was estimated positively and should be repeated in certain
      intervals. The used lists of queries were suitable. The valid rules and guide
      lines should be revised in near future.

PMID- 11963365
TI  - [CO2-stunning of slaughter pigs: effects on EEG, catecholamines and clinical
      reflexes].
AB  - Investigations were carried out on the response of slaughter pigs to CO2 stunning
      with two different gas concentrations (80 vol%, 90 vol%, 73 s) under practical
      conditions in a one gondola-dip-lift system. EEG measurements were performed and
      blood constituents such as catecholamines (adrenaline, nor-adrenaline) and
      lactate as well as clinical reactions (nasal septum and corneal reflex, heart
      beats) investigated. Special EEG-electrodes were adapted for the measurement on
      pigs and a mobile data logger was prepared for the use in the lairage of the
      slaughter house and in the stunning unit. The CO2 concentrations were measured
      continuously close to the head of the pigs when transported up and down in the
      stunning gondola. The results show that the technique is suited to monitor the
      effects of different CO2 gas concentrations on the EEG of the pigs under
      practical conditions. There is strong evidence that CO2 concentrations of 80 vol%
      applied over 70 s as required by law are not sufficient to stun pigs properly. A
      large part of the animals still showed typical reflexes when leaving the stunning
      pit. When an atmosphere of 90 vol% CO2 is applied, most animals are already dead
      before bleeding commences. This may create problems in respect to meat hygiene.
      The blood analysis revealed very high concentrations of catecholamines after
      stunning. The values for adrenaline and nor-adrenaline in the sticking blood rose
      by a factor of about 1000 as compared to the concentrations in blood samples
      taken in the lairage before stunning. It seems necessary to revise the current
      legislation on gas stunning and to look in greater detail in the effects of CO2
      stunning on the welfare of slaughter pigs.

PMID- 11963366
TI  - [Development of animal welfare legislation for the European Community].
AB  - Animal welfare is of increasing importance for the European Community, which is
      reinforced by the Protocol to the EC Treaty on protection and welfare of animals.
      After the recent improvements to the legislation on the protection of pigs, the
      next priority for the Commission is the further development of the standards of
      animal transportation, particularly since a report of the Commission pointed out
      shortcomings in the enforcement of the existing rules in this area.

PMID- 11963367
TI  - [Recent developments in animal welfare legislation (pig husbandry)].
AB  - Council Directive 91/630/EEC of 19 November 1991 laying down minimum standards
      for the protection of pigs has been amended in 2001. The following text provides
      a survey of the progress of the discussion at European level and of the options
      for transposing into national law.

PMID- 11963368
TI  - [Execution of the animal protection law (section 16a TierSchG)].
AB  - The measures of execution as laid down in section 16 a of the animal protection
      law (TierSchG) are of great importance in the daily work of the state offices for
      veterinary affairs to put an end to conditions of animal treatment offending
      against the law. Compared to the other available legal means 1. the
      administrative offences (fines) and 2. the penal law (fines or imprisonment) they
      offer the advantage that the guilt of the animal holder (intent or negligence)
      need not be proved. A thorough documentation of the controls made at the
      respective controlled place which offers evidence even in a trial is the main
      condition for carrying through effective measures of execution. To issue an
      administrative order requires in particular 1. to observe the principle of
      precision, 2. to fulfill the obligation to exercise discretion and 3. to provide
      well-founded reasons to support the decision of immediate execution. To be
      successful in court, certain basic requirements must also be fulfilled when a
      fine is imposed or a complaint is made by the state offices of veterinary
      affairs.

PMID- 11963369
TI  - [Killing of animals (a reasonable basis according to section 17 number 1 of the
      German Animal Protection Act?)].
AB  - The killing of cattle in order to support the market price, the millions of
      sorted male pullets or the killing of surplus animals in zoological gardens or
      breeds which do not have the right colour--the human way to deal with sentient
      creatures becomes more and more bizarre. How far is our treatment of animals
      compatible with the legal demand for killing a vertebrate animal only if a
      reasonable reason (also called good reason = vernunftiger Grund) according
      section 17 no. 1 of the German Animal Protection Act exists. An offence against
      this act could be punished with imprisonment up to three years or a fine.
      However, to constitute an offence is not necessarily illegal. The legislator has
      created the expression "reasonable reason" as an indefinite legal term. Therefore
      the animal protection law can further develop the legal term "reasonable reason"
      with the help of interpretation and dispensation of justice and adapt it to all
      social realities. Therefore an appropriate judgement on the killing of a
      vertebrate animal only is possible by viewing each individual case taking into
      regard all important factors of the relation between the animal and its owner.
      The killing of a vertebrate animal, which is found to be illegal according to
      section 17 no. 1 Animal Protection Act can not be punished in case special
      Community Law exists which has priority over national law. Community Law which
      cancels national law exists in the scope of housing, slaughtering and
      transporting of farm animals. There are loopholes in Community Law concerning the
      killing of domestic animals in their breeding that could be closed by national
      law. A solution to secure animal protection could be the creation of a strict law
      for the breeding of domestic animals in Germany.

PMID- 11963371
TI  - [Is cesarean necessary in all breech deliveries?].

PMID- 11963370
TI  - [Culling of animals in large herds, experiences from the Netherlands].
AB  - The outbreaks of classical swine fever in 1997-1998 and foot- and mouth-disease
      in 2001 provided a lot of experiences in the culling of animals. These
      experiences, as well as the aspects of animal welfare and public acceptance are
      described. In the future these experiences will help to carry out culling in a
      more efficient way including improved aspects of animal welfare and public
      acceptance.

PMID- 11963372
TI  - [Meteorology, climate and health].

PMID- 11963374
TI  - [Moral harassment in the hospital].

PMID- 11963373
TI  - [Employment, a declining value].
AB  - Because of increase in unemployment, and the consequent lack of job security and
      exclusion it leads to, the positive bond associated with work has, globally, been
      broken. Success both in professional and private life has become a competing
      aspiration, with a decreasing tendency to sacrifice one's private life for one's
      work. Physicians are also affected by this tendency and a major link has been
      broken in the attachment of the medical corps to their work. The fact that work
      is considered as a declining value, also in the health sector, corresponds to
      specific economic and societal phenomena. The repositioning of health in the
      economic activity, the re-definition of the medical professions with their
      specific competence, are presently under discussion.

PMID- 11963375
TI  - [Monitoring the incidence of multidrug-resistant bacteria in microbiology
      laboratories using Bacterio software].
AB  - INTRODUCTION: Since 1997, the microbiology laboratory of the hospital center in
      Lens has monitored hospital ecology and epidemiology to provide rapid information
      that help to adapt probabilistic antibiotherapy and to estimate the impact of
      hygienic preventive measures on the incidence of multidrug-resistant bacteria
      (MRB). METHODS: Monitoring with statistical software (Epi-Info) could be pursued
      and improved on with Bacterio, a specific software for microbiology laboratories.
      We studied the incidence of MRB not only in clinical specimens but also in
      ecologic specimens to detect BMR colonization. RESULTS: In the year 2000, the
      incidence reached 4.11 for 1000 hospitalization days and 3.34 for 100 admissions.
      This clearly differed from clinical activity. From 1998 to 2000 the incidence of
      BMR remained stable. BMR was detected within 48 hours after admission in 22.9% of
      cases. Methicillin-resistant Staphylococcus aureus and ticarcillin-resistant
      Pseudomonas aeruginosa were the most common BMR in our hospital. Extended broad
      spectrum beta-lactamase enterobacterii and Acinetobacter baumannii represented
      respectively 23% and 13% of the MRB. Stenotrophomonas maltophilia represented a
      minority and no vancomycin-resistant enterococci were found. CONCLUSION: Bacterio
      is a software well adapted to the use of microbiological data banks. Continuous
      monitoring of the incidence of BMR is very useful in the clinical care and
      hospital hygiene units.

PMID- 11963376
TI  - [Risk factors for the acquisition of Pseudomonas aeruginosa in a surgical
      intensive care unit].
AB  - OBJECTIVES: To investigate the risk factors for the acquisition (infection and/or
      colonization) of Pseudomonas aeruginosa, which is frequently associated with
      nosocomial infections, in a surgical intensive care unit in Dijon. METHOD: A
      retrospective case-control study was performed on 57 cases matching with 114
      controls, between December 1996 and February 1999. The statistical method used
      was a conditional multiple logistic regression model. RESULTS: Three groups of
      variables were studied (patient characteristics--invasive procedures--previous
      administration of antibiotics). The multiple logistic regression analysis
      confirmed 3 risk factors: duration of sedation, infection with another bacteria
      and cranio-encephalic trauma. These factors are commonly involved in nosocomial
      infections. CONCLUSION: This study confirms the interest of infection control
      measures and the prevention of nosocomial infections, especially in cranio
      encephalic trauma. The hypothetical relationship between acquisition of
      Pseudomonas aeruginosa and previous administration of antibiotics was not
      confirmed. A more powerful study would perhaps specify this relationship.

PMID- 11963377
TI  - [Isolation of three species of Nocardia in a patient receiving long-term
      corticosteroid therapy].
AB  - INTRODUCTION: Nocardia are saprophyte bacteria of the environment responsible for
      systemic infections in immunodepressed patients, due essentially to long-term
      corticosteroids. OBSERVATION: A patient having received corticosteroids for
      sarcoidoses for a year was hospitalised because of disseminated granulomatosis
      (neurological, respiratory, abdominal and cutaneous). Culture of various
      bacteriological samples isolated three species of Nocardia: N. otitidiscaviarum
      in uretheral pus and pus from the right gland, N. nova and N. asteroides in
      respiratory samples (protected distal sampling and broncho-alveolar washing).
      COMMENTS: Other than the mixed Nocardia infections described habitually,
      infections with two different species of Nocardia have recently been reported.
      Our case report is the first to have isolated three concomitant species of
      Nocardia.

PMID- 11963379
TI  - [Hyperchloremic metabolic acidosis during plasma volume replacement].

PMID- 11963378
TI  - [Treatment of anemia in chronic renal failure by a long-activing activator of
      erythropoiesis].
AB  - THE INTEREST AND LIMITS OF ERYTHROPOIETIN: Chronic renal failure (CRF) is often
      associated with anemia, mainly because of insufficient renal synthesis of
      erythropoietin (EPO). This observation led in the early 1980 to the cloning of
      the complementary DNA coding for the EPO molecule, the large-scale production of
      a recombinant human EPO (rHuEPO), and its large utilisation in clinical practice.
      More than a decade after this outstanding research progress, the use of rHuEPO
      has literally transformed the treatment of anemia of CRF. The efficacy of rHuEPO
      is dose-dependent and corrects the anemia in the majority of the patients.
      However, its relative short plasma half-live (4-8 hours) requires repeated
      injections of the drug, usually two to three times a week. A LONG ACTING
      ANALOGUE: The novel erythropoiesis stimulating protein (NESP) is a
      hyperglycosylated analogue of rHuEPO capable of stimulating erythropoiesis by the
      same mechanisms as the natural EPO. NESP possesses five N-linked oligosaccharide
      chains and two times more sialic acid residues than rHuEPO. The addition of these
      extra-carbohydrate chains gives NESP greater metabolic stability and a half-life
      3.6 times longer than rHuEPO. THE PROPERTIES OF NESP: Numerous studies have shown
      that NESP normalized and maintained stable the hemoglobin concentration when
      administered once a week and even at the frequency of one injection every other
      week. The optimal and maintenance dose is 0.45 microgram/kg/week, either
      intravenously or subcutaneously. Adverse events are similar to those seen with
      rHuEPO, and no antibodies against NESP have been detected in over 1,500 patients
      treated with NESP for more than 1 year. IN CONCLUSION: This novel long acting
      activator of the erythropoiesis is efficient and safe for the treatment of anemia
      of IRC patients. Its prolonged half-life, the delay between injections, and the
      decrease in the frequency of dose changes might result in an advantage for the
      patients and the medical staff.

PMID- 11963380
TI  - [Medical journals and bibliographic databases at the disposal of university
      hospitals for anesthesiologists in metropolitan France].

PMID- 11963381
TI  - [Diagnosis of ventilator-associated pneumonia: a prospective comparison of the
      telescoping plugged catheter with the endotracheal aspirate].
AB  - OBJECTIVE: Quantitative culture of endotracheal aspirates (EA) is widely accepted
      for the diagnosis of ventilator-associated pneumonia (VAP). The aim of the study
      was to compare the diagnostic accuracy of the EA with the blinded plugged
      telescoping catheter (PTC) in patients suspected of VAP. STUDY DESIGN:
      Prospective non-randomised observational study. PATIENTS AND METHODS: 31 patients
      suspected of having VAP underwent 46 bronchial samplings. An EA and a blinded PTC
      were performed successively in each case; the PTC result was taken as the
      reference standard. The EA and PTC cultures were defined positive if the result
      of bacterial cultures yielding were > or = 10(5) cfu.mL-1 and > or = 10(3) cfu.mL
      1 respectively. RESULTS: The diagnosis of VAP could be established in 19 cases
      when PTC was taking as gold test. The overall agreement between the two
      techniques was 76%. EA had a sensitivity of 89.5%, a specificity of 66.7%, a
      negative predictive value of 90% and a positive predictive value of 65.4%.
      CONCLUSION: EA is a good diagnostic test when a non-invasive test has been
      chosen. The diagnosis of VAP could be excluded in 90% of cases when the EA
      cultures yielding were < 10(5) cfu.mL-1. His low specificity could drive in an
      over treatment of bronchopulmonar bacterial colonization. The accuracy of the EA
      compares well with that of the TPC for the diagnostic of VAP.

PMID- 11963382
TI  - [Evaluation of regional anesthesia procedure in an emergency department].
AB  - OBJECTIVES: Evaluation of regional anaesthesia procedures for limb traumatic
      surgery performed in an emergency department. METHOD: Anaesthetic procedures
      concerning traumatic emergencies have been studied from 1995 to 2000. RESULTS: A
      32% increase in anaesthesia practice was observed from 1995 (221) to 2000 (292)
      with a 52% increase in regional anaesthesia. Since 1996, regional anaesthesia
      represents more than 80% of the anaesthetic procedures and 90% for the upper limb
      surgery (66% of the surgical procedures). Axillary block (50%), interscalene
      brachial plexus block (15%) and combined sciatic and femoral nerve block (17%)
      were the main regional anaesthesia procedures. Spinal anaesthesia (9 cases) and
      intravenous locoregional anaesthesia (12 cases) were rarely used. CONCLUSION: In
      our study, regional anaesthesia is the most used technique when compared to
      general anaesthesia for emergency procedure. The anaesthetic staff has to be
      motivated and trained.

PMID- 11963383
TI  - [Evaluation of an information document about patients and transfusion].
AB  - OBJECTIVE: To evaluate the understanding of written information contained in the
      information sheet for patients intended to receive an homologous transfusion and
      to know their opinion about this document. TYPE OF THE STUDY: A prospective
      cohort survey carried out by people unrelated to clinical units and transfusion
      services. METHODS: A document divided in two parts, the first one summarized, the
      second detailed, was distributed to transfused adult patients. The patients were
      hospitalized in the general surgery and orthopedic wards of two hospitals and in
      the hematology and oncology wards of two different hospitals. A questionnaire was
      filled out in the presence of the inquirer. RESULTS: Sixty one subjects have been
      enrolled, among them 53 considered the information as adequate; 53 as comforting
      and neutral. 53 patients considered a written information as essential and 52
      estimated that both part of the information sheet (summarized and detailed) were
      mandatory. Conversely, a more in depth investigation revealed there was a gap
      between patients statements and their true understanding. CONCLUSION: The value
      of a written information for the patients is confirmed by the study. In addition,
      patients were not generally worried by this information. The partition of the
      document has been appreciated. It is noteworthy that a gap exist between the
      patient's perception of the information and their actual level of understanding.

PMID- 11963384
TI  - [Comparison of nicardipine and isradipine in hypertension following coronary
      artery bypass graft].
AB  - OBJECTIVE: Compare the efficacy of isradipine to that of nicardipine for the
      control of arterial hypertension following coronary artery bypass graft (CABG).
      STUDY DESIGN: Clinical prospective, randomised study. MATERIAL AND METHODS: 40
      patients ASA II or III, mean age 66 +/- 8 years, scheduled for elective CABG were
      included. If the mean arterial pressure (MAP) was > or = 100 mmHg within the
      first six post operative hours, the patients were included and randomly
      attributed to either one of the 2 groups: Gr I (n = 20) received nicardipine, Gr
      II (n = 20) received isradipine in bolus then in continuous perfusion. HR, MAP,
      MPAP, CVP, PCWP, CI, SVRI, PVRI and SVI were recorded at: T0 before
      administration of drugs, T1 = 2 min after the first bolus. T2 when MAP reached 85
      +/- 5 mmHg. T3, T4, T5, T6, T7 and T8 at 5, 10, 30, 60, 90 and 120 min after the
      continuous perfusion. T9 before stopping the perfusion. RESULTS: No significant
      changes in HR, CVP, PCWP, MPAP or PVRI at any time in both groups. Significant
      increase in CI at T2 in both groups. Reduction of MAP at T2 was more important (
      27%) in Gr I compared to that in Gr II (-22%). This was mainly due to a
      significant decrease in SVRI. CONCLUSION: Isradipine is effective in the
      treatment of arterial hypertension following CABG. However there is not any
      significant beneficial effect of isradipine over nicardipine.

PMID- 11963385
TI  - [Hyperchloremic acidosis druing plasma volume replacement].
AB  - OBJECTIVES: Review of the physiological and clinical consequences of
      hyperchloraemic acidosis observed during plasma volume replacement using
      crystalloids and colloids. DATA SOURCES: Data were searched in the Medline
      database after 1990 using the following key words: metabolic acidosis,
      crystalloids, colloids, albumin, gelatin, hydroxyethyl starch. DATA EXTRACTION:
      Publications before 1990 were selected for their historical value. Most of
      articles published after 1990 and all types including case report were accepted.
      DATA SYNTHESIS: Large volume infusion of isotonic solution can cause
      hyperchloraemic acidosis. Colloid plasma substitutes using saline solvent may be
      responsible for the same kind of acidosis with acidaemia. The anion gap is not
      modified in this case because of chloride increase. Physiological mechanism may
      be described using the Henderson-Hasselbach equation or the strong ion difference
      decrease (Stewart concept). Excessive chloride infusion is a major factor in this
      acid-base disorder and the term hyperchloraemic acidosis should be preferred to
      dilutional acidosis. When perioperative acidosis occurs, careful and complete
      analysis of acid-base disturbance should be made. The association of a normal
      anion gap, normal lactatemia, hyperchloraemia and acidaemia does not need
      specific treatment. Acidosis corrects spontaneously and slowly following chloride
      normalization. But any factor that may increase acidosis should be avoided.
      CONCLUSION: The use of balanced solution like lactated-Ringer solution instead of
      isotonic saline solution for fluid resuscitation, except for specific contra
      indication as intracranial hypertension, may avoid hyperchloraemic acidosis.
      Potential risk of this acidosis led to the conception of a new colloid using
      balanced crystalloids solution as the solvent (Hextend).

PMID- 11963386
TI  - [Anaphylaxis after rocuronium: advantage of blood tests for early diagnosis].
AB  - A 56-year-old patient was scheduled for coronary artery bypass surgery, because
      of a severe coronary artery disease. Soon after induction of anaesthesia, he
      rapidly developed a cardiovascular collapse with bronchospasm and rash. Specific
      immunoglobulin E and tryptase measurements supported the diagnosis of grade III
      anaphylactic shock due to rocuronium bromide. A few days later, a general
      anaesthesia was administered without muscle relaxant and was uneventful.

PMID- 11963387
TI  - [Orbital exenteration: an unusual cause of failure of assisted ventilation from a
      face mask].
AB  - Orbitary exenteration for tumor may concern ethmoidal wall, and may create a
      large communication between the orbital cavity and the cavum. We present the case
      of a patient scheduled for ocular prosthetic surgery after an unilateral orbitary
      exenteration. After intravenous induction of the general anaesthesia,
      anaesthesiologist failed to achieve adequate facial mask ventilation because of a
      great gas leakage from cavum to orbital cavity. Inserting packing in the orbitary
      cavity allowed to decrease gas leakage and to get adequate facemask ventilation.
      We recommend orbitary radiographic and clinical evaluations for patient with
      orbitary exenteration before general anaesthesia to evaluate the communication
      between the orbital cavity and the cavum. Such an anatomic communication may
      result in inefficient facial mask ventilation.

PMID- 11963388
TI  - [Pneumocephalus after spinal anesthesia].
AB  - We report the case of a 76-year-old man who received a spinal anaesthesia for
      inguinal hernia repair surgery. A cranial CT scan which was performed because the
      patient complained of postoperative headache and hemiparesis showed an important
      pneumocephalus. Because postoperative questioning revealed that the patient had a
      chronic and neglected rhinorrhea, we hypothesise that this pneumocephalus was
      secondary to an old unknown osteodural leak with intracranial air entry secondary
      to the spinal anaesthesia-releated decrease in CSF pressure.

PMID- 11963389
TI  - [Spontaneous splenic rupture in the second quarter of pregnancy].
AB  - We report the case of a 33 year-old woman at the second quarter of pregnancy,
      with known brain aneurysm admitted in intensive care unit for sudden coma. The
      coma was not related to a rupture of the brain aneurysm but to a serious
      haemorrhagic shock caused by a spontaneous splenic rupture. This case report
      illustrates the difficulty of this unrecognized diagnosis and reminds us to
      suspect a spontaneous splenic rupture in front of any pregnant woman with atypic
      abdominal pain and haemorrhagic shock.

PMID- 11963390
TI  - [Survey of bibliographic facilities offered in departments of anesthesia and
      intensive care of French univeristy hospitals].
AB  - OBJECTIVES: We assessed bibliographic facilities offered in departments of
      anaesthesia (DA) belonging to university hospitals in metropolitan France.
      METHODS: We mailed a questionnaire to the 76 heads of DA belonging to university
      hospitals in France to assess: a) which journals dealing with anaesthesia,
      analgesia, and critical care were available, on site, for consultation; b)
      whether a medical library existed within the institution; and c) whether all
      bibliographic informations required by any DA collaborators were charged to the
      institution. RESULTS: We received 67 replies (87%). High impact factor revues had
      the widest availability rates--Anesthesiology: 67 DA (100% of responses)-
      Anesthesia Analgesia: 66 DA (98.5%)--the British Journal of Anaesthesia: 63 DA
      (94%). The Annales Francaises d'Anesthesie et de Reanimation were available in 66
      DA (98.5%). Ten journals in French were variably available--no journal: 1 DA
      (1.5%)--1 journal: 19 DA (28%)--2 journals: 34 DA (51%),--3 journals: 10 DA (15%)
      -4 journals: 3 DA (4%). Revues dealing with anaesthesia in specialised surgery
      were diversely available--neurosurgery: 7 DA (10%)--paediatrics: 10 DA (15%)-
      obstetrics: 11 DA (16%)--cardiovascular: 26 DA (39%). Revues dealing with pain
      management, regional anaesthesia or critical care were available in 29 DA (43%),
      32 DA (47%), and 59 DA (91%), respectively. The European Journal of
      Anaesthesiology was available in 40 DA (60%). Thirty-nine DA (58%) took charge of
      all bibliographic informations required. No medical library existed in 4
      university hospitals (6%). CONCLUSION: DA offers a wide variation in
      bibliographic facilities in French university hospitals.

PMID- 11963391
TI  - [Antibiotic prophylaxis in cardiac surgery: practice patterns].
AB  - OBJECTIVE: To assess the prescription patterns in French and foreign centres for
      antibiotic prophylaxis in cardiac surgery. MATERIAL AND METHODS: Phone and
      written surveys concerned 64 French and 70 foreign centres. It focused on the
      first injection, the duration of treatment and the recommended agents. RESULTS:
      87% of the French centres and 67% of the foreign centres answered the
      questionnaire. The first injection took place at anaesthesia induction in all
      French centres but during administration of premedication in 11% of foreign
      centres (p < 0.05). The duration of prophylaxis was restricted to the
      intraoperative period only in 20% and 15% of centres, respectively (ns), as
      specified by the recommendations. No French centres carried on the antibiotics
      more than 48 h versus 11% of foreign centres (p < 0.05). Cephalosporines of the
      second generation were prescribed in 84 and 49% of centres, respectively (p <
      0.05). The combination of two antibiotics was less frequent in France than in
      foreign countries (5 versus 17%, p < 0.01). In absence of betalactamin allergy
      glycopeptides were not utilized in France versus 8% in foreign countries (p <
      0.05). In case of allergy vancomycin was used in 66% of French and 42% of foreign
      centres. CONCLUSION: The French recommendations may have influenced favourably
      the antibiotic choice but the prophylaxis duration was too long in most of the
      non French European centres.

PMID- 11963393
TI  - [Post-traumatic lumbar extradural hematoma].

PMID- 11963392
TI  - [Laryngeal dyspnea in adults: think about the epiglottis].

PMID- 11963394
TI  - [From a consensus conference to AMM (authorization to market): succinylcholine as
      an example].

PMID- 11963395
TI  - [Myocardial preconditioning and its practical significance].
AB  - The authors review the history and physiological basis of myocardial
      preconditioning including its receptors, signalization and effectors. The
      classical and delayed (second window) type of preconditioning and relations of
      the latter to heat shock proteins are discussed. Preconditioning as a form of
      endogenous adaptation effectively reduces the degree of myocardial injury during
      a subsequent ischaemia in experimental models and in human as well. Intentional
      triggering or augmentation of the condition may become a new therapeutic tool in
      the treatment of ischaemic diseases. Utilizing the advantages of endogen
      adaptation, the optimal drug or procedure to be applied in the routine clinical
      practice will come out in the future considering its efficacy and the safety and
      convenience of the patient.

PMID- 11963396
TI  - [Changes in calcium metabolism after parathyroidectomy in primary
      hyperparathyroidism].
AB  - INTRODUCTION: Primary hyperparathyroidism causes elevated serum calcium level and
      osteopenia in most patients. AIMS: The authors measured the changes of calcium
      and bone mineral metabolism after parathyroidectomy in patients with primary
      hyperparathyroidism. PATIENTS: From 1995 to 2000, osteopenia was detected in 34
      patients with primary hyperparathyroidism before surgery. There were 26 females
      (16 women were post-menopausal) and 8 males. The mean age of the patients was 54
      years (range 19 to 64). The serum levels of calcium, phosphorus, alkaline
      phosphatase and the parathyroid hormone were measured before the operation and
      every year thereafter. Bone densitometry was performed at the lumbar spine (L II
      IV) during the same period. RESULTS: The mean levels of calcium and parathyroid
      hormone rapidly decreased and varied in the normal range after the operation. The
      mean alkaline phosphatase concentrations also decreased after surgery, but in
      most cases the difference was not statistically significant. Bone densitometry
      showed increased bone mineral density at the lumbar spine (L II-IV) after the
      parathyroidectomy. One, 2, 3, 4 and 5 years after surgery the bone mineral
      density increased with 8.5%, 12.5%, 14.1%, 13.5% and 11.3% compared to the
      preoperative value respectively. The changes in bone mineral density values were
      not statistically significant 1 year after parathyroidectomy. The increase in the
      bone mineral density was significant two years after the operation. Nine patients
      had T-scores less than -2.5 before parathyroidectomy. CONCLUSION: The authors
      conclude, that the serum levels of calcium and parathyroid hormone significantly
      decreased after the parathyroidectomy in primary hyperparathyroidism. After
      successful surgical treatment the bone mineral density significantly increases
      and the osteopenia decreases or resolves.

PMID- 11963397
TI  - [Serum tumor marker levels during a 12-months growth hormone replacement therapy
      in patients with adult growth hormone deficiency].
AB  - INTRODUCTION: High growth hormone/insulin-like growth factor-1 level may have
      oncogenic potential in animal experiments, and in patients with acromegaly. There
      are also some data suggesting the development of different neoplasms in animals
      after growth hormone administration and in humans upon growth hormone replacement
      therapy. AIMS: The general opinion is however, that growth hormone replacement
      therapy has no oncogenic effect, but the tumor marker levels have not been
      studied so far. PATIENTS/METHODS: Nine patients participated in the study: 3
      women, 6 men, aged between 21-52 years. 6 of them had multiple pituitary hormone
      deficiency and were on replacement therapy (thyroxine: 2, cortisone: 1, sexual
      steroids: 6 and desmopressin: 2 patients). The cause of growth hormone deficiency
      was the removal of pituitary tumor (6 patients) or craniopharyngioma (2
      patients), and in 1 case the deficiency was idiopathic. The mean dose of growth
      hormone was 0.53 in female and 0.51 mg/day in male patients. Insulin-like growth
      factor-1, carcinoembryonal antigen, human choriogonadotropin hormone, alpha
      fetoprotein, prostate specific antigen, tissue polypeptide antigen-M, ferritin,
      gastrointestinal carcinoma antigen, ovarian antigen, breast specific antigen,
      carcinoma antigen 50 were measured at baseline and after 3, 6 and 12 months of GH
      replacement. RESULTS: Insulin-like growth factor-1 standard deviation score
      increased: baseline: -4.1 +/- 0.5; 3 months: -0.3 +/- 0.3; 6 months: 0.7 +/- 0.2;
      12 months: -0.2 +/- 0.6, P < 0.001 vs. baseline. The mean value of all tumor
      markers remained within the normal range and there was no significant increase
      within the normal range either. CONCLUSION: The lack of increase of tumor marker
      levels does not indicate possible oncogenic effect of one-year GH treatment in
      hypopituitary adults. The authors can not draw any far-reaching conclusions
      because of the low patient number and the short follow-up, but the measurement of
      tumor marker levels may provide useful means to follow up long-term therapy and
      for the early diagnosis of possible occult malignancy.

PMID- 11963398
TI  - [Panniculitis-like lymphoma clinically manifesting as alopecia].
AB  - A 45-year-old female patient discussed herein had a multifocal, alopecia areata
      of inflammatory character. Histological findings first suggested histiocyte
      cytophagic panniculitis, although a "burned-out" panniculitis-like T-cell
      lymphoma could not be excluded. After a two-year follow-up period assessment of
      the T-cell receptor gene rearrangement verified the diagnosis of subcutaneous
      panniculitis-like T-cell lymphoma. This case is interesting because of its
      isolated manifestation and a long-standing, benign course of the disease.

PMID- 11963399
TI  - [Albert Szent-Gyorgyi--biography of a free genius].

PMID- 11963400
TI  - [Nobel Prizes first given in 1901].

PMID- 11963401
TI  - [Pathogenesis of systemic lupus erythematosus].

PMID- 11963402
TI  - [12th International Conference of Heat Technology and Thermography, Budapest, 13
      15 June 2001].

PMID- 11963403
TI  - [Treatment of upper gastrointestinal bleeding caused by peptic ulcer].
AB  - INTRODUCTION: The diagnosis and treatment of gastrointestinal bleeding represent
      a major problem even today. Nearly 50% of upper gastrointestinal bleedings are
      originating from peptic ulcers of different locations. Thanking to the modern
      gastroenterological treatment the number of elective operations carried out
      because of peptic ulcers is very low. On the other hand the number of urgent
      operations required by the complications--mainly by bleeding--of the ulcers is
      still rather high. AIM: Summarizing the possible treatments of these patients.
      METHODS AND DISCUSSION: The therapeutic endoscopy accompanied by the medical
      treatment has the primary role in the treatment of bleeding peptic ulcers. If
      this treatment fails, the surgical treatment is mandatory. Also surgical
      treatment is necessary in case of massive rebleeding. These kinds of operations
      are accompanied by a high morbidity and mortality, so it is understandable that
      the surgeons are trying to avoid them. After spontaneous or successful endoscopic
      cessation of bleeding in some cases rebleeding can be expected. The probability
      of rebleeding can be predicted with the consideration of predictive factors. With
      the help of such prognosis we can decide the indication of "early elective
      operation". In the surgical treatment we can expect better results with more
      "aggressive" type of operations (resections). The delay of an indicated
      operation, or repeatedly carried out endoscopic and medical treatment can reduce
      the survival chance of the bleeding patients. CONCLUSIONS: The treatment of upper
      gastrointestinal bleeding is a multidisciplinary task, which needs the correct
      cooperation of gastroenterologists, intensive therapists and surgeons.

PMID- 11963405
TI  - [Dental screening of patients after organ transplantation].
AB  - INTRODUCTION: Before any organ transplantation, the patient undergoes a wide
      range of medical controls and is prepared for the surgical intervention, which
      lasts for several hours and imposes considerable stress on the organism; the
      patient is also prepared so as to be able to tolerate the subsequent lifelong
      need for immunosuppressive treatment. AIMS: A study was made of wether dental
      foci are eliminated appropriately in practice, and wether the necessary dental
      follow-up is performed. PATIENTS/METHOD: During a period of 10 months, 55
      patients presented at the above Department for the control screening of dental
      foci an average of 27.5 months after organ transplantation. Physical and X-ray
      examinations were performed and the numbers of dental focal lesions were
      determined. RESULTS: The examinations revealed lesions that could be regarded as
      dental foci in 34.5% of the cases, and in many there were multiple (on average
      2.7) focus-suspect lesions. In one case, the possibility arose of a health
      impairment connected with the inadequacy of the dental treatment. The last dental
      control examination had been made on average 22.4 months before the current focus
      screening. CONCLUSIONS: This study suggests the need for the uniformity of the
      principles of dental focus screening and dental care in patients awaiting organ
      transplantation and lifelong immunosuppressive treatment, for more systematic
      care in practice, and for the organization of regular dental controls in these
      patients.

PMID- 11963404
TI  - [Therapeutic possibilities in axonal injury caused by head trauma].
AB  - Traumatic brain injury is putting an extreme burden on societies all over the
      world. While surgical and neuro-intensive treatment is traditionally aimed at
      space occupying or focal lesions, traumatic brain injury is frequently associated
      with diffuse axonal injury, which significantly contributes to its morbidity and
      mortality. Current taught appreciates that diffuse axonal injury is a progressive
      event gradually evolving from focal alterations in axolemmal permeability and the
      underlying axonal ultrastructure to axonal disconnection, a process amenable of
      therapeutic interventions. This review is primarily focusing on the
      clinical/neuroradiological manifestation and our contemporary knowledge of the
      pathobiology of traumatically evoked (diffuse-) axonal injury with particular
      emphasize on recent- to date, primarily experimental-therapeutic approaches that
      in the future might offer potential aid to the head injured.

PMID- 11963406
TI  - [Amastia--pregnancy--delivery].
AB  - The author describe bilateral amastia in a young woman. The genital organs
      function perfectly. She become two times pregnant. First she gives birth a normal
      boy. Second gestation she let interrupted.

PMID- 11963407
TI  - [Istvan Rothman (1894-1963)].

PMID- 11963409
TI  - [Scientometrics of medical journals in the forefront again in Hungary].

PMID- 11963408
TI  - [Tuberculosis, leprosy, syphilis and cancer research--trends of development.
      1935].

PMID- 11963410
TI  - [Memory of Dr. Somogyi in diabetology].

PMID- 11963411
TI  - Intranet lights up radiology.

PMID- 11963412
TI  - One finger vs. many passwords.

PMID- 11963413
TI  - Obstacles block path to increased use of I.T. in disease management.

PMID- 11963414
TI  - Internet helps whittle down transactions costs.

PMID- 11963415
TI  - I.T. often a tough sell to nursing staffs.

PMID- 11963416
TI  - Do employees make the grade?

PMID- 11963417
TI  - Reader's perspectives. Health care organizations should put the identifier rules
      of the Health Insurance Portability and Accountability Act on the back burner.

PMID- 11963418
TI  - Managing leg ulcers.

PMID- 11963419
TI  - Non-antiseptic cleansing of traumatic wounds.

PMID- 11963420
TI  - How to choose the correct pressure-relieving cushion.

PMID- 11963421
TI  - When and how to use hydrogels.

PMID- 11963422
TI  - Understanding Pseudomonas aeruginosa.

PMID- 11963423
TI  - Preparing patients with asthma for discharge.

PMID- 11963424
TI  - Churg-Strauss syndrome.

PMID- 11963425
TI  - Malignant pleural mesothelioma.

PMID- 11963426
TI  - A guide to assessing sputum.

PMID- 11963427
TI  - Changing for the better.

PMID- 11963428
TI  - Hang on to your rights when faced with a sell-off.

PMID- 11963429
TI  - Reflections from a nursing home.

PMID- 11963430
TI  - Choosing a pressure ulcer risk assessment tool.

PMID- 11963431
TI  - A proud tradition.

PMID- 11963432
TI  - Setting up a residential screening programme.

PMID- 11963433
TI  - Back to basics: continence.

PMID- 11963434
TI  - Report cards don't make the grade with physicians or consumers.
AB  - Not popular with physicians or consumer, but they help with quality improvement
      initiatives.

PMID- 11963435
TI  - Labor costs for knee surgery bend downward.
AB  - Study highlights most efficient practices in arthroscopic knee surgery

PMID- 11963436
TI  - On-line tool kit makes PI meetings obsolete.

PMID- 11963437
TI  - Improved accuracy from point-of-care heparin tests.

PMID- 11963438
TI  - Patient safety alert. Early results of Leapfrog hospital survey promising.

PMID- 11963440
TI  - Patient safety alert. Safety tool stresses education and action.

PMID- 11963442
TI  - Mapping capacity in the health sector: a conceptual framework.
AB  - Capacity improvement has become central to strategies used to develop health
      systems in low-income countries. Experience suggests that achieving better health
      outcomes requires both increased investment (i.e. financial resources) and
      adequate local capacity to use resources effectively. International donors and
      non-governmental agencies, as well as ministries of health, are therefore
      increasingly relying on capacity building to enhance overall performance in the
      health sector. Despite the growing interest in capacity improvement, there has
      been little consensus among practitioners and academics on definitions of
      'capacity building' and how to evaluate it. This paper aims to review current
      knowledge and experiences from ongoing efforts to monitor and evaluate capacity
      building interventions in the health sector in developing countries. It draws on
      a wide range of sources to develop (1) a definition of capacity building and (2)
      a conceptual framework for mapping capacity and measuring the effects of capacity
      building interventions. Mapping is the initial step in the design of capacity
      building interventions and provides a framework for monitoring and evaluating
      their effectiveness. Capacity mapping is useful to planners because it makes
      explicit the assumptions underlying the relationship between capacity and health
      system performance and provides a framework for testing those assumptions.

PMID- 11963441
TI  - Prescription practices of public and private health care providers in Attock
      District of Pakistan.
AB  - The irrational use of drugs is a major problem of present day medical practice
      and its consequences include the development of resistance to antibiotics,
      ineffective treatment, adverse effects and an economic burden on the patient and
      society. A study from Attock District of Pakistan assessed this problem in the
      formal allopathic health sector and compared prescribing practices of health care
      providers in the public and private sector. WHO recommended drug use indicators
      were used to study prescription practices. Prescriptions were collected from 60
      public and 48 private health facilities. The mean (+/- SE) number of drugs per
      prescription was 4.1 +/- 0.06 for private and 2.7 +/- 0.04 for public providers
      (p < 0.0001). General practitioners (GPs) who represent the private sector
      prescribed at least one antibiotic in 62% of prescriptions compared with 54% for
      public sector providers. Over 48% of GP prescriptions had at least one injectable
      drug compared with 22.0% by public providers (p < 0.0001). Thirteen percent of GP
      prescriptions had two or more injections. More than 11% of GP prescriptions had
      an intravenous infusion compared with 1% for public providers (p < 0.001). GPs
      prescribed three or more oral drugs in 70% of prescriptions compared with 44% for
      public providers (p < 0.0001). Prescription practices were analysed for four
      health problems, acute respiratory infection (ARI), childhood diarrhoea (CD),
      fever in children and fever in adults. For these disorders, both groups
      prescribed antibiotics generously, however, GPs prescribed them more frequently
      in ARI, CD and fever in children (p < 0.01). GPs prescribed steroids more
      frequently, however, it was significantly higher in ARI cases (p < 0.001). For
      all the four health problems studied, GPs prescribed injections more frequently
      than public providers (p < 0.001). In CD cases GPs prescribed oral rehydration
      salt (ORS) less frequently (33.3%) than public providers (57.7%). GPs prescribed
      intravenous infusion in 12.3% cases of fever in adults compared with none by
      public providers (p < 0.001). A combination of non-regulatory and regulatory
      interventions, directed at providers as well as consumers, would need to be
      implemented to improve prescription practices of health care providers.
      Regulation alone would be ineffective unless it is supported by a well
      established institutional mechanism which ensures effective implementation. The
      Federal Ministry of Health and the Provincial Departments of Health have to play
      a critical role in this respect, while the role of the Pakistan Medical
      Association in self-regulation of prescription practices can not be
      overemphasized. Improper prescription practices will not improve without consumer
      targeted interventions that educate and empower communities regarding the hazards
      of inappropriate drug use.

PMID- 11963443
TI  - A policy of introducing a new contract and funding system of general practice in
      Estonia.
AB  - The socialist bloc of post-war Europe was obliged to follow the Soviet example
      with a hierarchical, centrally controlled health care system based on polyclinics
      and other facilities providing extensive specialist services at the first level
      of contact. All the countries of Central and Eastern Europe have now expressed
      their wish to totally change their health care systems. Changes in these
      countries include: the introduction of market economy mechanisms in health care,
      an increased focus on population health needs in guiding health care systems, and
      the possibility of introducing a more general type of care at primary level.
      Patient expectations of access, choice and convenience are factors in shaping new
      models of health care delivery. Appropriate timing is the key determinant of the
      success of reforms. In Estonia the beginning of the 1990s was the time when
      several interest groups in society supported changes in the health care system.
      The first step after regaining independence was the reintroduction of a Bismarck
      type insurance system. In the late 1990s the primary care reforms have changed
      the initial plans and elements of a National Health Service were introduced,
      especially general practitioners' lists, capitation payment and gate-keeping
      principles. The family medicine reform in Estonia has two main objectives:
      introduction of general practice as a specialty into Estonian health care and
      changing the remuneration system of primary care doctors. The specific tasks are:
      to provide practising primary care doctors with opportunities for retraining to
      gain the specialty status of a general practitioner, to create a list system for
      the population to register with a primary care doctor, to introduce a partial
      gate-keeping system and to give the status of the independent contractor to
      primary care doctors.

PMID- 11963444
TI  - Differences in health insurance and health service utilization among Asian
      Americans: method for using the NHIS to identify unique patterns between ethnic
      groups.
AB  - The purpose of this study is to outline a method to identify the characteristics
      of socioeconomic variables in determining the differences in health insurance
      coverage and health services utilization patterns for different ethnic groups,
      using the behavioural model of health service utilization. A sample drawn from
      Asian American adult respondents to the 1992, 1993, and 1994 National Health
      Interview Surveys (NHIS) in the USA formed the data set. The results showed Asian
      Americans as not being homogeneous. There were distinctly different demographic
      and socioeconomic characteristics between six Asian American ethnic groups that
      affect health insurance coverage and health service utilization. The study method
      is useful for constructing health policy and services to address the general
      public need without adversely affecting smaller minority groups. Secondary
      analysis of well-constructed national data sets such as the specific Asian ethnic
      groups in NHIS, offers a rich method for predicting the differential impact of
      specific health policies on various ethnic groups.

PMID- 11963445
TI  - The performance of material management in health care organizations.
AB  - This paper studies the hospital supply chain. The analysis of the operational and
      financial data of hospital administrative structures has permitted the discovery
      of the characteristics of work carried out by the employees and the different
      strategies used by the managers. Firstly, hospital supply chains must be
      classified into two groups influenced by medical factors (short-term and long
      term hospitals). Secondly, two different management approaches can be observed
      when the supply chain operations are analysed. The first approach assigns a
      larger budget priority to inventory control, packages reception and internal
      distribution. Thus, the purchasing services have relatively fewer resources. In
      the second approach, contract negotiation and product ordering processes are
      enforced by the deployment of, relatively, more personnel. In both cases, the
      central store service performs merchandise reception and distribution according
      to the strategies determined by the purchasing service.

PMID- 11963446
TI  - Palliative care--or is it?

PMID- 11963447
TI  - A prospective, within-patient comparison between metal butterfly needles and
      Teflon cannulae in subcutaneous infusion of drugs to terminally ill hospice
      patients.
AB  - We performed a prospective study of hospice in-patients requiring a syringe
      driver (SD), to determine the site duration and tolerability of metal butterfly
      needles compared to Teflon cannulae. Using patients as their own control,
      prescribed medications were divided equally between two SDs (Graseby MS16a), for
      delivery over 24 h. A butterfly infusion (Flosafer, 25 gauge) was connected to
      one SD and a Teflon cannula (Abbocath-T, 24 gauge), to the second. These were
      inserted subcutaneously (s.c.) on opposite sides of the body at comparable sites;
      oedematous, broken or painful sites were excluded. SD sites were examined at 4
      hourly intervals. The study was terminated when both devices had required
      resiting. Needle and cannula times were compared using the Wilcoxon signed rank
      test. Thirty patients entered the study, 13 males and 17 females, mean age
      (standard deviation): 70 (11) years. Thirteen patients completed the study. Nine
      patients died and eight patients discontinued the study before both needle and
      cannula had been resited. All 30 patients are included in the analysis. The time
      from insertion to resiting of the cannula was significantly longer than the
      needle: P < 0.0002, median (range) 93.5 (22.8-263.5) h versus 42.8 (7.5-162.3) h,
      respectively. The cost of the needle versus cannula is 1.93 Pounds versus 2.51
      Pounds, respectively. Teflon cannulae have a median life span twice that of metal
      butterfly needles and are a cost-effective alternative for administration of
      medications by s.c. infusion in terminally ill patients.

PMID- 11963448
TI  - Euthanasia and physician-assisted suicide in Scandinavia--with a conceptual
      suggestion regarding international research in relation to the phenomena.
AB  - This article analyses and compares recent research on Scandinavian physicians'
      attitudes towards, as well as their practice of, euthanasia and physician
      assisted suicide. The studies discussed are quite dissimilar in their design,
      resulting in considerable difficulties as far as comparability is concerned. Such
      difficulties are common in these fields of research. As an intended contribution
      to the amendment of future research, we suggest what we take to be detailed and
      precise definitions of the terms euthanasia and physician-assisted suicide for
      use internationally. Our definitions, or interpretations, basically draw on the
      Dutch experience and understanding of these terms. The Dutch approach implies
      that acts of abstention from life-prolonging treatment, i.e., withholding and
      withdrawing treatment, and pain and symptom treatment that theoretically could
      shorten life (including terminal sedation) are to be considered 'normal medical
      practice'. Furthermore, death is seen as having natural causes in all of these
      acts. That, however, is not the case with euthanasia and physician-assisted
      suicide. When a physician performs either of these acts, he or she is required to
      state 'unnatural death' in the patient's death certificate. Our conceptual
      suggestions do not address the ethical status of the various medical decisions
      that are made with regard to the death of patients; our aim is conceptual clarity
      only. As far as euthanasia and physician-assisted suicide in Scandinavia is
      concerned, even though comparisons prove difficult, we do think some observations
      may be made: physicians from Norway, Denmark and Sweden display differences in
      both attitude and practice concerning these phenomena. Norwegian physicians are
      most restrictive with regard to attitude. Danish and Swedish physicians display a
      more liberal attitude, the latter being the most liberal. These findings did not
      fit the physicians' practice. Danish physicians have performed euthanasia and
      physician-assisted suicide more often than Norwegian physicians. Swedish
      physicians, even though they are the most liberal when it comes to attitude,
      appear never to have performed euthanasia and very seldom physician-assisted
      suicide.

PMID- 11963449
TI  - Nutritional status of patients with advanced cancer: the value of using the
      subjective global assessment of nutritional status as a screening tool.
AB  - In patients suffering from advanced neoplastic disease, malnutrition is a common
      complication affecting both the survival and quality of life. In order to monitor
      early dietary interventions, an assessment of patients' nutritional status is
      essential. We assessed the nutritional status of 46 patients using two different
      methods: 1) an objective method of nutritional assessment and 2) the subjective
      global assessment (SGA) technique. It was found that 28 patients were
      characterized as malnourished by means of the objective method and 30 patients
      according to the SGA. The correlation of the results of the assessments between
      the two methods was high and a validation test of the SGA gave a sensitivity of
      96% and specificity of 83%. The most frequent symptoms affecting food intake were
      anorexia, early satiety, dry mouth, pain and nausea. The results show that the
      SGA represents an easy method for assessment of the nutritional status in such
      cancer patients and that it can therefore be used as a screening tool. The high
      incidence of malnutrition in this group of patients, and their rare use of
      nutrient supplements, both indicate the importance of early nutritional
      assessment, and nutritional intervention when appropriate.

PMID- 11963450
TI  - Lack of concealment may lead to selection bias in cluster randomized trials of
      palliative care.
AB  - Comprehensive palliative care programs are often implemented on a community
      level, and to evaluate such interventions, randomization by cluster (community)
      may be the only feasible method. In trials randomizing individual subjects, the
      importance of proper concealment has been stressed. In cluster randomized trials,
      however, concealment of individual patient allocation is often impossible. The
      following risk of selection bias has been given little attention. In the present
      study, comparing palliative care to conventional care, community health care
      districts were defined as clusters and randomized. The patients' treatment
      assignment was determined by the allocation of the cluster in which they resided,
      and hence predictable by their address. A biased selection based on practical
      considerations related to patients' diagnoses and hospital departments was
      suspected. To explore this, cancer diagnoses were grouped according to local
      tradition for sharing of treatment responsibility among hospital departments. A
      significant difference between trial arms in distribution of these groups was
      revealed and strongly supported our suspicion. The finding carries an important
      message to future researchers: when using cluster randomization, any evidence of
      selection bias should be carefully checked and reported.

PMID- 11963451
TI  - Palliative care and policy in England: a review of health improvement plans for
      1999-2003.
AB  - Since 1987 health authorities in England have been required to make plans for
      palliative care provision, but their record in doing so has been patchy. The
      production of health improvement plans (HlmPs), in which each health authority
      must set out its priorities and actions designed to improve the health and well
      being of its local population, provides an opportunity to examine the extent to
      which palliative care provision in the NHS is regarded as a priority by policy
      makers in England. This paper reports on a structured documentary review of the
      HlmPs published by the 99 health authorities in England. The review indicates
      that at the moment, in spite of the longstanding duty placed on health
      authorities to develop strategic plans for palliative care and to assess the
      level of local palliative care needs, not all have made significant progress in
      this direction. Among those that do have plans for palliative care, the vast
      majority of these plans are for people with cancer. What emerges most clearly is
      a sense in which specialist palliative care, especially for non-cancer patients,
      is perceived as an 'optional extra' by many health authorities rather than an
      integral and essential part of the overall supportive care strategy which they
      clearly are at pains to develop.

PMID- 11963452
TI  - Assessing education in palliative medicine: development of a tool based on the
      Association for Palliative Medicine core curriculum.
AB  - The Association for Palliative Medicine (APM) of Great Britain and Ireland has
      developed a core curriculum for palliative medicine. To establish the
      appropriateness of this core curriculum as a standard against which training can
      be measured, we have examined how doctors from different medical, social and
      cultural backgrounds view its various elements. In 1998, we succeeded in tracing
      304 of 390 doctors, past students of the University of Wales College of
      Medicine's Diploma in Palliative Medicine. Each was sent a postal questionnaire
      that asked them to rate the importance to their own clinical practice of each
      element of the APM core curriculum. Two-hundred sixty-three questionnaires were
      returned--a response rate of 87%. The ages ranged from 30 to 71 (mean 44) years;
      56% (147) were female. Forty per cent (105) were general practitioners, and 37%
      (97) hospice and 23% (61) hospital-based. Eighty-three per cent (220) were from
      the UK, 5% (14) from the rest of Europe, 8% (21) from the Far East and 3% (8)
      from other countries. The majority of respondents agreed that all elements of the
      APM core curriculum were of 'very great' or 'great' importance to their current
      clinical practice. Respondents' medical, social or cultural setting had only very
      minor effects on their attitude to individual elements. The elements of the
      curriculum perceived as being of greatest importance were: communication with
      patients and their families, assessment, diagnosis and treatment of pain,
      multiprofessional team working and psychological responses to illness and
      bereavement. Clinicians from a wide variety of backgrounds confirm the relevance
      of the APM core curriculum. This justifies its adoption as the audit standard
      against which the quality of training and educational programmes in Palliative
      Medicine should be judged.

PMID- 11963453
TI  - Daily journal club: an education tool in palliative care.
AB  - Journal clubs are a valuable tool for medical education. This paper describes a
      unique daily journal club format utilized by our palliative care programme and
      presents the results of a questionnaire sent to trainees exploring satisfaction
      with its educational value. We reviewed the number and type of articles presented
      at the journal club over 1 year. A questionnaire was mailed to participating
      family medicine residents and palliative care fellows. The number of articles
      presented over 1 year was 252. Pain and symptom control, psychosocial issues and
      drugs other than opioids were topics accounting for 72% of the presentations.
      Half were given by attending physician staff, 38% by trainees and 12% by
      multidisciplinary visitors. Palliative care fellows indicated significantly
      higher levels of satisfaction than family medicine residents, particularly in the
      areas of clinical applicability, acceptability of the daily schedule and overall
      educational value. The increased emphasis on evidence-based practice in
      palliative care suggests that a journal club could be a useful educational tool.
      The results from our experience could be applied to other palliative care
      programmes.

PMID- 11963454
TI  - Radiotherapy for the palliation of high-volume pleural effusion in malignant
      mesothelioma: case report.

PMID- 11963455
TI  - Palliative care: are we talking about the same patients?

PMID- 11963456
TI  - Percutaneous decompression in acute bowel obstruction associated with pelvic
      malignancy.

PMID- 11963457
TI  - Cluster-randomized trials.
AB  - Cluster-randomized trials represent an important experimental design,
      supplementing ordinary randomized clinical trials. They are particularly relevant
      when evaluating interventions at the level of clinic, hospital, district or
      region. They are necessary when it is not feasible to randomize individual
      patients, and desirable when there may be contamination between clusters. But
      they also carry serious design and analysis implications, and the use of clusters
      as the unit of randomization must be justified. Sample sizes will usually need to
      be greatly increased, an adequate number of clusters is essential, and the
      statistical analysis must allow for the cluster design. And one should rigorously
      guard against selection bias.

PMID- 11963458
TI  - Hallucinations in an elderly cancer patient: opioid neurotoxicity or dementia
      with Lewy bodies?

PMID- 11963459
TI  - Molecular mechanisms underlying the breakdown of gametophytic self
      incompatibility.
AB  - The breakdown of self-incompatibility has occurred repeatedly throughout the
      evolution of flowering plants and has profound impacts on the genetic structure
      of populations. Recent advances in understanding of the molecular basis of self
      incompatibility have provided insights into the mechanisms of its loss in natural
      populations, especially in the tomato family, the Solanaceae. In the Solanaceae,
      the gene that controls self-incompatibility in the style codes for a ribonuclease
      that causes the degradation of RNA in pollen tubes bearing an allele at the S
      locus that matches either of the two alleles held by the maternal plant. The
      pollen component of the S-locus has yet to be identified. Loss of self
      incompatibility can be attributed to three types of causes: duplication of the S
      locus, mutations that cause loss of S-RNase activity, and mutations that do not
      cause loss of S-RNase activity. Duplication of the S-locus has been well studied
      in radiation-induced mutants but may be a relatively rare cause of the breakdown
      of self-incompatibility in nature. Point mutations within the S-locus that
      disrupt the production of S-RNase have been documented in natural populations.
      There are also a number of mutants in which S-RNase production is unimpaired, yet
      self-incompatibility is disrupted. The identity and function of these mutations
      is not well understood. Careful work on a handful of model organisms will enable
      population biologists to better understand the breakdown of self-incompatibility
      in nature.

PMID- 11963460
TI  - Sexual mimicry in hyenas.
AB  - Genital masculinization in female spotted hyenas has been widely explained as an
      incidental consequence of high androgen levels. High androgen levels, in turn,
      were supposed to be favored because they led to adaptive aggressive behavior.
      Incidental androgenization is no longer a tenable hypothesis, however, because
      genital masculinization has been shown to proceed in the absence of androgenic
      steroids. Thus, an alternative hypothesis is required. The genitals of spotted
      hyena females are not simply masculinized, but exhibit a detailed physical
      resemblance to the male genitalia. In the absence of satisfactory alternative
      explanations, we propose that selection may have favored sexual mimicry in
      females because they are more likely than males to be targets of aggression from
      other females. Male-like camouflage could theoretically be protective in three
      contexts: neonate sibling aggression, infanticide by conspecific females, and
      interclan territoriality. Current data suggest that if sexual mimicry is
      important, its effects are strongest among infants.

PMID- 11963461
TI  - [Correcting spinal malformations during the growth period: classic task of
      orthopedics].

PMID- 11963462
TI  - [Personal charges of emergency patients].

PMID- 11963463
TI  - [Ehlers-Danlos syndrome. A review].

PMID- 11963464
TI  - [Idiopathic scoliosis and Scheuermann's kyphosis. Historical and current aspects
      of conservative treatment].
AB  - Although in practice since antiquity the nonoperative treatment of spinal
      deformities is still controversial. Giving preference to orthotic treatment and
      physiotherapy the historical development of nonoperative treatment will be
      demonstrated by the examples of idiopathic scoliosis and Scheuermann's kyphosis.
      It is surprising how early essential and still valuable principles of
      nonoperative treatment had been acquired and how many of the present-day concepts
      have remarkable forerunners in the 19th century. In the light of previous
      knowledge and personal experience the indication, practice and realistic
      capabilities of modern nonoperative treatment of idiopathic scoliosis and
      Scheuermann's kyphosis are pointed out.

PMID- 11963466
TI  - [Surgical treatment of idiopathic scoliosis and juvenile kyphosis].
AB  - Indication for operative treatment of idiopathic scoliosis and juvenile kyphosis
      is mainly cosmetic. There is also a higher incidence of pain in scoliosis
      patients, and reduced pulmonary function in severe deformity, especially in
      severe deformities present at the age of 5 years (early onset). Scoliotic curves
      of less than 30 degrees will not progress in adults, whereas curves of 50-75
      degrees will further progress a mean of 25 degrees during 40 years. Progression
      in adults with juvenile kyphosis is not well documented. Operative treatment aims
      to stop progression, to control spinal growth, or to perform correction and
      fusion by spinal instrumentation and bone grafts. These goals can be achieved
      either by an anterior, a posterior, or a combined approach. Correction principles
      are compression, distraction, derotation and translation. The forces applied by
      correction are transferred by fixation devices (pedicle screws, anterior screws,
      hooks, sublaminar wires) to the spine. The higher correction forces are, the
      higher is the correction achieved, but also the risk of fracture and torn out
      implants. Mobilisation reduces rigidity and allows to achieve a better correction
      with equal forces. The best mobilisation techniques are disc excision, facet
      joint removal, and techniques to mobilise the thorax.

PMID- 11963465
TI  - [Spinal growth under physiological and pathological conditions].
AB  - Spinal growth is developing analogously to extremity growth. As the vertebral
      spine is built by 25 "vertebral units" there are much more possibilities of
      compensatory growth in short parts of pathologic alterations than there are in
      cases of affected extremities that only show epiphyseal compensations in
      metaphyseal or diaphyseal deformities (such as juvenile fractures). The dynamics
      of growth is different in the spine. The neurocentral epiphysis, basis to seize
      of spinal channel, shows very strong dynamics in embryonal and early childhood
      growth corresponding to the development in central nerve system. Whereas,
      enchondral height growth of vertebral bodies does not end after puberty, in male
      sex even at about the age of eighteen. Enchondral growth of the spine is much
      more sensible to affections than periostal growth. This is analogous in the
      extremities. Spinal growth is determined genetically, but especially in puberty
      it can be influenced by the child's posture. This is a therapeutic hint
      especially for the period of fast vertebral growth in puberty. The strong
      straightening tendency of spine is fascinating. Thus, in the period of growth all
      spinal deformities are compensated by the vertebral segments below and above, so
      that the axis appears in horizontal line and the spine altogether in
      perpendicular position.

PMID- 11963467
TI  - [Congenital anomalies of the spine].
AB  - Congenital anomalies of the spine usually originate in (toxic) disturbances
      during pregnancy. There are occasional hereditary types. These are characterized
      by the presence of multiple anomalies. Congenital scolioses are often associated
      with other anomalies like spinal dysraphy (20-30%) and fusion of the ribs.
      Furthermore heart defects, Sprengel's deformity, cleft palates, hemimelias,
      clubfeet or congenital vertical talus are frequently associated with congenital
      scoliosis. We classify in failures of formation, segmentation and combined types.
      The type of malformation determines the prognosis. One hemivertebra is associated
      with a risk of progression of 0-2 degrees/year, 2 ipsilateral hemivertebra with 2
      3 degrees/year, a unilateral unsegmented bar with 5 degrees/year and a
      combination of a unilateral unsegmented bar with a contralateral hemivertebra
      with approximately 10 degrees/year. Conservative treatment is usually
      ineffective. The indication for operative treatment should be made before the
      deformity becomes unacceptable, as a correction is difficult and dangerous. The
      following operations can be carried out: Anterior and/or posterior fusion with or
      without instrumentation, epiphyseodesis, (hemi)vertebrectomies (with anterior
      and/or posterior approach), distraction with a halo, osteotomies, separation of
      the fused ribs and gradual distraction (Campbell's expansion thoracoplasty). The
      operations carry significant risks and the indication to the various treatment
      modalities is difficult. Operations should be made under monitoring of sensory
      and motor evoked potentials. From 498 patients with congenital anomalies of the
      spine in our observation we have operated on 143. Hemivertebrectomies were the
      most frequent interventions (56).

PMID- 11963468
TI  - [Intraspinal malformations. Tethered cord syndrome].
AB  - The importance of intraspinal malformations associated with "tethered cord"
      (attachment of the spinal cord) has increased in recent years, because of better
      imaging methods using nuclear magnet resonance (MRI). Orthopedic malformations
      such as club feet, equinus deformity, lordosis, hip dislocation, kyphosis, and
      differences of leg lengths, which up till now have been mostly treated by
      orthopedic surgeons, are usually first examined for congenital anomalies.
      According to the results of this examination, a neurosurgical operation for
      untethering is performed. The aim of our study is to define spinal malformations
      more exactly and to elucidate their importance for orthopedics. In addition,
      indications for operating, operative aims, diagnosis, therapy and follow-up are
      discussed. Examples of our results are shown, and the significance for
      interdisciplinary cooperation is emphasized.

PMID- 11963469
TI  - [Neurogenic spinal deformities. I. Conservative and surgical treatment of spinal
      deformities].
AB  - Neurogenic spinal deformities develop primarily due to insufficient dynamic
      stabilization against gravity. Unilateral muscle overactivity is another but rare
      cause. The aim of treatment is to provide stability as well as to prevent
      deformity. In mild cases, the treatment of choice is a spinal brace because
      stabilization can be combined with residual mobility and adequate correction of
      shape. Seating shells are more readily accepted but less appropriate for this
      purpose. In severe cases, surgery is a good option despite the considerable
      effort involved and high rate of complications.

PMID- 11963470
TI  - [Neurogenic spinal deformities. II. Sitting and seating devices: principles and
      indications].
AB  - Sitting is a dynamic process regulated by motor reactions due to endogenic and
      exogenic influences. Patients with neuromuscular disorders may not continuously
      adapt their sitting posture but seating devices may improve their quality of
      life. Prerequisites for the indication of high quality and cost effective seating
      devices are guidelines for planning and fitting which consider both
      pathomorphologic mechanisms and the patient's personality. In order to avoid
      functional problems and pain caused by an insufficient seating device it is
      necessary to pay attention to the exact indication, time, and combination of
      technical options. Planning within a seating clinic needs teamwork. First the
      goal of treatment is defined; it depends on the functional deficit, on the daily
      living activities of the patient, and on the social environmental factors. Second
      fitting of the devices follows defined treatment guidelines. By examination of
      the sensoric and statomotoric system it is possible to classify the patient's
      sitting or seating ability for simplifying indication: three groups of active
      sitters who are able to change position of trunk and pelvis actively are
      differentiated from three groups of passive sitters who have to be seated.

PMID- 11963471
TI  - [Pediatric spinal injuries].
AB  - Spine injuries during growth are rare, but in comparison to adults they are more
      often associated with neurologic impairment. They also may occur without visible
      injuries in X-rays. The problems of conventional radiologic diagnostics include
      before all the differential diagnosis between synchondrosis, apophysis and
      fracture lines. MRI is indicated in case of neurologic deficits without
      radiologic abnormalities. In principle the fracture types correspond to those
      seen in adults. In addition growth specific injuries of the end-plates (growth
      plates) or ring apophysis may occur. Stable compression fractures are treated
      conservatively. The spontaneous remodelling capacity for posttraumatic
      deformities decreases with age: in children below the age of ten years the
      remodelling capacity for posttraumatic kyphosis is excellent whereas deformities
      in the frontal plane show no or only incomplete remodelling. Unstable fractures
      and injuries with associated compression of neural structures should be treated
      conservatively.

PMID- 11963472
TI  - [Spondylodiscitis in childhood].
AB  - Spondylitis is a rare disease in childhood and atypical symptoms frequently
      retard the diagnosis. From 1968 to 1988, 25 children with a diagnosis of
      spondylitis were treated in our orthopedic hospital. Anamneses, clinical
      symptoms, roentgenograms, and differential diagnoses are described for these
      cases. Spondylodiskitis represents a mild course of the disease in childhood.
      Tuberculous spondylitis was not present in any of the cases. The prognosis of
      childhood spondylitis is favorable, and surgical interventions were not necessary
      in our patients. Spondylitis healed with an ankylosis of one segment of the spine
      without essential disturbance of spinal function.

PMID- 11963473
TI  - [Spondylolysis and spondylolisthesis during growth].
AB  - Spondylolysis and Spondylolisthesis present with typical age and activity-related
      issues: in newborns the pars interarticularis is always intact. Only bipedal
      ambulators develop spondylolysis, mostly during early childhood. Corresponding to
      the mechanical etiology, the incidence of spondylolysis is higher in athletes who
      repeatedly have to hyperextent and rotate their lumbar spine for example
      gymnasts, javelin throwers etc. Spondylolysis is one of the most frequent
      diagnosis among adolescents with lumbar back pain. However, most of the people
      with an interrupted Pars interarticularis (about 6% of the population) never
      become symptomatic or if they do, they respond very well to conservative
      treatment (adaptation of physical activity, active physical therapy and bracing).
      If pain persists in combination with an intact intervertebral disc of the slipped
      segment, we recommend a direct repair of the Pars interarticularis instead of an
      intersegmental fusion. Patients with low grade Spondylolisthesis (Meyerding I,
      II) require repeated radiological follow-up during growth because of the inherent
      risk of slip progression. If a slip of more than 50% is detected before the end
      of growth, operative treatment is indicated. High grade olisthesis (Meyerding
      III, IV) leads to anterior shift of the whole trunk, kyphosis of the slipped
      vertebra with subsequent compensatory lumbar hyperlordosis and flattening of the
      thoracic spine. Pelvic flexion is clinically evident. Reduction of the slipped
      and kyphotic vertebra with correction of the spinal, sacral and pelvic profile is
      recommended and preferable to simple fusion in situ.

PMID- 11963474
TI  - [Dislocation of the tendon of the ulnar extensor muscle of the wrist. Important
      differential diagnosis of ulnar wrist pain].
AB  - Undefined pain of the ulnar wrist often poses diagnostic and therapeutic problems
      for the physician. Without proof of a definite cause, the diagnosis of damage to
      the triangular discus is frequently given.

PMID- 11963475
TI  - [Epidemiology of limb fractures].
AB  - To analyze age- and sex-specific frequencies of peripheral fractures, we used
      data from the third MONICA-Augsburg Survey (1994/95). The study comprises 2404
      male and 2450 female participants (age 25 to 74 years) who were questioned
      regarding fracture history. We investigated fracture prevalence, age-specific
      incidence rates, and the circumstances under which the fractures occurred. The
      age-standardized, cumulative fracture prevalence among men (m) 25 to 74 years of
      age was 45% and among women (w) of the same age 31%. Fracture prevalence among
      women was more than 10% lower than among men in the younger age groups (age 25 to
      64 years), but after an significant increase in the 65 to 74-year-olds the
      fracture prevalence corresponded to that of men (m: 42%, w: 40%). A peak of
      incidence rates was found among men at age 15-24 (overall incidence rate: 2017
      fractures/100,000 person-years) and at age 45-54 (overall incidence rate: 1640
      fractures/100,000 PY), respectively, and among women at age 65-74 (overall
      incidence rate: 3214 fractures/100,000 PY). The prevalence of self-reported
      osteoporosis (age 25 to 74 years) was higher in women (7%) than in men (1%).
      Falls caused 43% (w: 59%, m: 33%) of all fractures, external violence 40% (m:
      47%, w: 29%), and sports activities 15% (m: 18%, w: 10%). Further investigation
      of risk factors related to fractures can contribute to the development of
      specific preventive measures in that field. In the future, the prevention and
      efficient treatment of an existing or an often undiagnosed osteoporosis and also
      the prevention of falls in elderly persons should be an important public health
      concern.

PMID- 11963476
TI  - [Sonography -- an established means of diagnosis in orthopedics].

PMID- 11963477
TI  - [Standardized sectional planes of the locomotor apparatus].
AB  - Comparable to the standardized ultrasound screening of newborns and infants
      according to Graf's method, the standardized ultrasound examination of the
      locomotor apparatus has become an important feature in the evaluation of many
      acute and chronic diseases. The standardized ultrasound examination technique
      according to the guidelines of DEGUM and DGOOC helps the experienced and
      inexperienced user to avoid diagnostic mistakes by reproducibly displaying
      anatomical landmarks. Specific individual planes can be necessary in certain
      indications. The main advantage in comparison to other diagnostic means (i.e.,
      computed tomography and magnetic resonance imaging) lies in the possibility of
      dynamic examination, which allows excellent imaging especially in rotator cuff
      affections. In cases without pathological findings, two standardized planes have
      to be documented. Otherwise, the pathological finding has to be documented in two
      standardized planes. The standardized procedure is a useful means for assuring
      and improving the quality of sonographic examinations of articular and
      periarticular structures.

PMID- 11963478
TI  - [Ultrasonic anatomy of pediatric joints].
AB  - The radiological work-up of joint injuries in young children can be very tedious
      due to the absent ossification of secondary ossification centers, which cannot be
      seen directly on plain X-ray images in this age group. Cartilaginous joint
      structures therefore cannot be distinguished from joint gaps using X-ray images
      in young children. High-resolution ultrasound scanning probes facilitate
      ultrasound studies of cartilaginous joint structures and growth plates in young
      children, thus providing a new and rewarding option for imaging of traumatic
      alterations of growing joints, especially in children whose secondary
      ossification centers have not yet undergone calcification processes. The use of
      ultrasound for evaluation of joint injuries avoids the shortcomings of ionizing
      radiation, contralateral joints can be examined for comparison, and functional
      dynamic studies can be obtained easily.

PMID- 11963479
TI  - [Ultrasonography in trauma].
AB  - The aim of this paper is to report on the possibilities of ultrasonography of the
      musculoskeletal system following traumatic injuries. Subsequent to clinical and
      radiologic examination, ultrasonography is able to confirm the primary diagnosis
      by dynamic comparison with a minimal expenditure of time and costs. The size,
      extent, and anatomic topography of tissue lesions are depicted. This paper
      focuses especially on the diagnosis of fluid within joints and soft tissues, the
      identification of foreign bodies, the diagnosis and follow-up of fractures, the
      diagnosis of infections (possibility of sonographically guided puncture), and
      musculotendinous injuries. Furthermore, the use of ultrasonography for the
      evaluation of postoperative pain and complications, the preoperative planning of
      metal removals, and its performance during spinal surgery are discussed. This
      paper deals with indications and technical tips for sonography as well as
      methodological limitations and sources of error in the evaluation of
      ultrasonographic findings.

PMID- 11963480
TI  - [Ultrasonography in inflammatory rheumatic diseases].
AB  - In addition to clinical and laboratory findings, ultrasound is a very useful
      imaging procedure for the diagnosis of all rheumatic diseases. This method is
      able to monitor their development and dynamics. All joints that can be reached by
      the ultrasound beam are examined (from large ones such as the shoulder and knee
      to small ones such as fingers and toes) with various techniques and different
      frequencies.

PMID- 11963481
TI  - [Ultrasonography of tumors of the locomotor system].
AB  - Sonography is an integral part of primary tumor diagnosis and follow-up for the
      great majority of organ systems. However, its value in the field of space
      occupying processes of the locomotor system, especially of malignant bone tumors,
      has mostly been underestimated. The sonographic examination has to investigate
      the whole tumor region and the corresponding lymph nodes statically and
      dynamically. The examination procedure should be standardized and the
      documentation reliable. Evaluation criteria are the localization, dimensions, and
      volume of the tumors, echogenicity and homogeneity, peri- and intratumoral
      vascularization (vessel density and architecture), borders of the tumor, and
      neighboring structures. Pathologic changes not only of the soft tissues but also
      of the bones can be evaluated sonographically. Even subtle analysis does not
      permit definitive assessment of tumor status. Taking its physical limitations
      into consideration, high-resolution sonography, enhanced by color/PowerDoppler
      and three-dimensional techniques, is a valuable adjunct to improve diagnosis,
      therapy planning, monitoring, and posttherapeutic care of tumors of the locomotor
      system.

PMID- 11963482
TI  - [Muscle ultrasound in neuromuscular diseases].
AB  - Imaging modalities are the only noninvasive methods that provide morphological
      information on skeletal muscles. In neuromuscular diseases, electrodiagnostic
      investigations are routinely employed in the diagnostic process, although they
      only deliver functional information. Thus, imaging and electro-diagnostic methods
      are not in competition, but complement each other. Each method has its specific
      indications. The technique and diagnostic value of muscle ultrasound in
      neuromuscular diseases are presented in this review.

PMID- 11963483
TI  - [Possibilities and limitations of ultrasonography in corticotomy/callus
      distraction].
AB  - Sonographic examination can yield additional information free of radiation in the
      course of corticotomy/callus distraction. The echogenic structures of the
      cortical structure and the callus between can be scanned at the area of the
      callus distraction by ultrasound examination. Individual sectional planes are
      focussed. They are different from the standardized ultrasound examination.
      Depending on when the corticotomy was performed, the callus between the cortical
      structures can be visualized sonographically. First it is echo poor, and then it
      becomes more and more echogenic. The ultrasound examination can give additional
      information during the first 4 weeks after corticotomy/callus distraction. A
      deviation of the axis in the area of callus distraction cannot be judged
      reliably. A sonographically guided division into three stages is possible.

PMID- 11963484
TI  - [Quantitative ultrasound (ultrasonometry) in the diagnosis of osteoporosis. State
      of the art].
AB  - The importance of ultrasound-based measuring methods in the diagnosis of
      osteoporosis has increased during the last few years. Measuring speed of sound
      (SOS) and broadband ultrasound attenuation (BUA) also allows assessment of
      density and elasticity of bone. Values measured show significant age dependence
      and correlate well with osteoporotic bone deterioration. The various ultrasound
      methods are quite equal and allow an adequate prediction of fracture risk
      comparable to the radiologic dual energy X-ray absorptiometry (DEXA) method. At
      present, standardization of cutoff points and criteria to determine osteoporosis
      among the different devices is unsatisfactory. The suitability of the method for
      a general screening is growing.

PMID- 11963485
TI  - [Ultrasound examination of the hip. An update].
AB  - Hip sonography has continued to progress in terms of its quality and standards.
      Error analyses showed that the most common misdiagnoses are caused by the false
      anatomical identification of an echo, by insufficient or missing verification of
      usability, by inadequate knowledge of exceptions as well as by defective
      technical equipment. The correct examining technique is independent from the
      skills of the examiner; the use of linear scans equipped with 7.5-MHz transducers
      in most cases, for bigger infants with 5-MHz transducers, is obligatory. Two
      sonograms in the standard range with a magnification scale of 1:1.7 are required;
      positioning devices and probe guiding systems are indispensable instruments for
      avoiding tilting effects. Colleagues in practice who finished their training more
      than 5 years ago are strongly advised to attend at least a 1-day refresher course
      to fulfill their obligation for further education. In the future, type-related
      therapy including the three main treatment phases reposition, retention, and
      postmaturation must be considered more often than before. Noncompliance with
      standards and the resulting misdiagnoses have already led to the first juridical
      consequences, i.e., claims for damages.

PMID- 11963486
TI  - [Three-dimensional techniques in orthopedic ultrasonography].
AB  - Three-dimensional ultrasonography is not yet an established method in soft tissue
      and joint diagnostics as it is in obstetrics. Although a spatial view on the
      object is fascinating, problems occur in handling. No standard is defined for
      acquisition or visualisation. For the acquisition of the volume mainly 3D-arrays
      and image correlation techniques are used. For visualisation planar views of
      sections out of the volume, but also spatial views in a transparency or surface
      mode are used. Investigations on feasibility for soft tissue or joints show a
      higher accuracy, validity and reproducibility for 3D-sonography. Due to the low
      differences of the acoustic impedance visualisation is confusing in a
      transparency mode and needs a time consuming postprocessing in a surface mode.
      Future developments address to the field of faster acquisition ("real time 3D"),
      higher geometric precision and easier visualisation by automated segmentation. By
      the three-dimensionality of the data set applications in telematics, navigation
      and simulation ("sonographic training") are expected.

PMID- 11963487
TI  - [New ultrasound techniques].
AB  - Modern ultrasound technologies can be divided into methods of visual image
      improvement/presentation, image quantification, and echo contrast agent
      applications. Image improvement can be realized by options such as Photopic,
      tissue harmonic imaging, and panorama methods. Parametric ultrasound quantifies
      observer-independent image textures. Echo contrast agents offer a better
      detection of tumor lesions and vascular kinetic investigations.

PMID- 11963488
TI  - [Running training courses and seminars in sonography. Guidelines of the German
      Society of Orthopedics and Orthopedic Surgery, German Society of Ultrasonography
      in Medicine and Physicians Association].

PMID- 11963489
TI  - [Low-grade central osteosarcoma . 3 case reports].
AB  - Low-grade central osteosarcoma is a well-differentiated subtype of osteosarcoma,
      which is often confused with benign lesions. Males and females were affected
      about equally in our study. The tibia and femur were most commonly involved.
      Three case reports demonstrate the distinct features of the tumor. Excision of
      the tumor almost invariably led to recurrences. Wide resection was almost never
      followed by recurrence and seems to be the treatment of choice for this very rare
      variant of osteosarcoma.

PMID- 11963490
TI  - [Iliopsoas impingement after cementless total hip arthroplasty. Case reports].
AB  - Postoperative pain after total hip arthroplasty can be caused by several
      conditions. We describe two cases of postoperative persistent iliopsoas
      impingement after cementless implantation of the acetabular component. The groin
      pain was relieved after revision with a more anteverted acetabular component. We
      describe the diagnostic methods as well as the principles of the revision.

PMID- 11963491
TI  - [The medicine advertising law and the practicing physician. An introduction to
      the problem].

PMID- 11963492
TI  - [Fundamentals and methods of conservative treatment of fractures].

PMID- 11963493
TI  - [Intraoperative parathyroid hormone monitoring in neck exploration for renal
      hyperparathyroidism?].
AB  - INTRODUCTION: In operations for renal hyperparathyroidism the value of
      intraoperative parathormone monitoring was investigated. PATIENTS AND METHODS:
      Intraoperative intact parathyroid hormone levels were determined (PTH Quick
      assay) in 40 patients undergoing first cervical exploration and in two patients
      with graft-dependent recurrence of renal hyperparathyroidism. RESULTS: In 33
      patients, total parathyroidectomy with autotransplantation was carried out. The
      median parathormone levels decreased from 652 pg/ml to 120 pg/ml (19% of initial
      level) 5 min after total parathyroidectomy. In seven patients, fewer than 4
      parathyroid glands each were identified during cervical exploration and "total
      parathyroidectomy (?)" without autotransplantation was performed.
      Intraoperatively median parathormone level decreased from 1193 pg/ml to 116 pg/ml
      (10% of initial level). In one of these seven patients, hyperparathyroidism
      persisted due to an ectopic fourth gland within the carotid sheath. In two of
      these patients, hypoparathyroidism occurred and a delayed autotransplantation of
      cryopreserved parathyroid tissue was carried out. On the first day after total
      parathyroidectomy with autotransplantation and "total parathyroidectomy (?)",
      median levels of intact parathyroid hormone were 1.9 pg/ml and 82.5 pg/ml,
      respectively. CONCLUSION: Intraoperative monitoring is not useful in first
      cervical exploration for renal hyperparathyroidism because it cannot predict
      complete resection of parathyroid tissue. The parathormone level on the first
      postoperative day allows precise evaluation of the efficacy of the surgical
      procedure.

PMID- 11963494
TI  - [Esophageal perforation. Etiology, diagnosis, therapy].
AB  - METHOD: Between 10/1997 and 2/2000 we treated eight patients (-66.5 y, 31-92 y, 5
      male, 3 female). These cases were analyzed retrospectively. RESULTS: In one case
      the the perforation was located in the cervical part, in three cases in the
      intermediate part, and in four cases in the distal part oesophagus. In seven
      cases the perforation was caused by endoscopic and one acid burn in suicidal
      intention. Surgical treatment was performed in seven cases (87.5%), five of them
      with primary suture, two with primary esophageal resection. The mortality rate
      was 50%. There was no insufficiency of the suture, but two patients died because
      of pulmonary complications, one patient with known hepatic cirrhosis (Child C)
      because of an uncontrollable bleeding of his fundus and esophageal complications
      5 days after successful surgical treatment, and one patient because of fulminant
      sepsis after dislocation of an enteral catheter. Three of the patients were
      operated within 12 hours after perforation, seven of them were operated within
      less than 24 hours. CONCLUSIONS: Surgical treatment of esophageal perforation
      within 24 hours after perforation shows good results. The outcome of the
      treatment depends on whether there are postoperative pulmonary complications and
      concomitant diseases. Enteral nutrition should be avoided in cases of primary
      esophageal resection to facilitate the surgical reconstruction at the second
      operation.

PMID- 11963496
TI  - [Nissen and Toupet laparoscopic fundoplication in patients with gastroesophageal
      reflux and motility disorders of the distal esophagus].
AB  - INTRODUCTION: A Nissen fundoplication for gastrooesophageal reflux disease may
      more often lead to persistent dysphagia than a Toupet fundoplication. The aim of
      this study was to assess the results of laparoscopic Nissen versus Toupet
      fundoplication in patients with reflux disease and impaired distal esophageal
      motility. PATIENTS AND METHODS: In 15 patients a laparoscopic Nissen and in 17 a
      laparoscopic Toupet fundoplication was carried out. Criteria for an impaired
      motility of the distal esophagus were a mean amplitude of < 30 mm Hg of swallow
      induced contractions, or > 33% non-propulsive or non-transmitted contraction
      waves. Before surgery, heartburn, dysphagia, regurgitation and other symptoms
      were scored and endoscopic, manometric and 24 hour pH-metric investigations
      performed. Patients were reinvestigated 3 to 30 (median 15) months after Nissen
      and 3 to 42 (median 7) months after Toupet fundoplication. RESULTS: After Nissen
      as well as after Toupet fundoplication heartburn was significantly less frequent,
      whereas dysphagia and all other symptom-scores remained unchanged. In the 26
      patients reinvestigated manometrically, the resting pressure of the lower
      esophageal sphincter was significantly higher following both operations and the
      residual sphincter pressure upon swallowing higher only after Nissen
      fundoplication. The amplitude of swallow-induced contractions and the percentages
      of non-propulsive and non-transmitted contraction waves were not significantly
      changed after either operation. In the 23 patients restudied pH-metrically,
      reflux activity was significantly reduced after both Nissen and Toupet
      fundoplication. CONCLUSION: In patients with reflux disease and impaired distal
      esophageal motility, laparoscopic Nissen and Toupet fundoplication both yielded
      satisfactory results and neither operation led to increased dysphagia.

PMID- 11963495
TI  - [Esophageal resection in treatment of achalasia. 4 case reports and review of the
      literature].
AB  - In the time period between 1985 and June 2001, four of 81 patients diagnosed with
      achalasia were surgically treated by means of transhiatal esophageal resection.
      Replacement with stomach and cervical anastomosis was performed in three patients
      aged 8, 19, and 27 years, respectively, after initial myotomy. In one case, the
      esophagus resection was the primary surgical measure and the colon was used as
      the replacement. The preoperative symptoms of the four patients showed
      improvement 51, 34, 15, and 8 months after the operation, respectively. Dysphagia
      and regurgitation no longer occurred. One patient died 4.5 years after esophageal
      resection due to ulcerous bleeding of the distal redundant colon interposition.
      In accordance with other studies investigating serious swallowing disorders, it
      could be shown that transhiatal resection with esophagus-replacement through
      stomach pull-up can lead to symptom-relief as well as an improvement in the
      quality of living.

PMID- 11963497
TI  - [Adenomas of Vater's ampulla and of the duodenum. Presentation of diagnosis and
      therapy by endoscopic interventional and surgical methods].
AB  - BACKGROUND: Adenoma of the ampulla of Vater and the duodenum are rare tumors. The
      leading symptoms are unspecific; sometimes they are due to the disturbances of
      the passage or erosion of the tumor. Early and correct diagnosis and the
      appropriate therapy are of decisive importance because these tumors are
      precancerous. PATIENTS AND METHODS: We report the cases of seven patients with
      periampullary adenoma of the duodenum, in one case with incorporation of the the
      distal bile duct. The diagnostic steps and the surgical treatment are reported
      and discussed. In achieving a definitive diagnosis, endoscopic retrograde
      cholangiopancreatography is of paramount importance. Three patients subsequently
      underwent partial pancreatoduodenectomy (Whipple's procedure); in three patients
      transduodenal local tumor excision was performed. Postoperative course was
      without complications in each case and no operative mortality occurred. One
      patient was treated by argon-coagulation. RESULTS: The histopathological
      examination showed a tubular villous adenoma in six cases and in one case a
      villous adenoma (ranging from low to high grade dysplasia). Because there is
      evidence of an adenoma-carcinoma-sequence, radical surgical treatment is
      recommended, even in adenoma with low grade dysplasia, in spite of the absence of
      malignancy.

PMID- 11963498
TI  - [Radical resection of colorectal carcinoma in the oldest old].
AB  - INTRODUCTION: The percentage of old people with colorectal cancer is steadily
      increasing in Western industrialized countries. Since there are only a few
      reports on the extent of surgery, it is unclear whether radical lymphadenectomy
      can also be safely performed as a standard operation in this age group. METHODS:
      In a prospective study, we analyzed all patients who were > or = 80 years of age
      at the time of surgery and who were submitted to surgery between 1/95 and 12/00
      due to a colorectal carcinoma. Target parameters were postoperative morbidity and
      mortality. RESULTS: Fifty-seven of 665 patients (8.6%) were > or = 80 years of
      age. The median age was 85 years (range: 80-92). The gender ratio was 1:1.6
      (G:E). Palliative surgery was performed in 19 of 57 patients. The remaining 38
      patients underwent curative radical lymphadenectomy; 32 were elective and 6
      emergency procedures. Mean ASA scores were 2.1 +/- 0.3 and 2.5 +/- 0.6. The
      following operations were performed: 13 right-sided and 15 left-sided
      hemicolectomies, 5 rectal resections, 3 rectal extirpations and 2 Hartmann's
      procedures. Two anastomotic insufficiencies (6%) had a complication-free course
      after revision. The rate of major surgical complications was 11%, that of
      internal complications 16%. Three patients (8%) died, one after an elective
      procedure and two after emergency laparotomy. One of the latter was an 89-year
      old woman who refused to undergo a revision due to bleeding after Hartmann's
      procedure. Pneumonia and myocardial infarction were the cause of death in the
      other two patients. CONCLUSION: Radical resection can be safely performed even at
      an advanced age. Since age-corrected survival is comparable to that of younger
      patients, surgery should be performed in the elderly under elective conditions
      according to oncological criteria.

PMID- 11963499
TI  - [Local recurrence and survival rate after rectal cancer operations and multimodal
      therapy].
AB  - INTRODUCTION: In the guidelines of the German specialist medical societies,
      postoperative chemoradiotherapy is recommended for rectal carcinomas in stages II
      and III. In the meantime, there are important study findings favoring
      preoperative radiotherapy as against postoperative irradiation. In the present
      unicentric study, the clinical results after preoperative irradiation and
      postoperative chemotherapy are to be determined. In period I, sandwich radiation
      without total mesorectal excision was applied. In period II, the treatment was
      developed further with exclusive preoperative radiation and total mesorectal
      excision. Since from 1994 the therapy regimen has changed with the introduction
      of total mesorectal excision and improved radiotherapy, the present study was
      carried out to check whether this has led to better results of therapy. PATIENTS
      AND METHODS: Over a period of 7 years, data from 607 patients with rectal
      carcinoma were recorded and stored in an Excel file. The carcinomas were grouped
      into lower, middle and upper segment levels and classified endosconographically.
      Multimodal treatment was administered in stage uT3. In period I, sandwich
      radiation was carried out with 24 Gy preoperatively and 24 Gy postoperatively,
      followed by adjuvant chemotherapy. Total mesorectal excision was not performed.
      In period II, 50.4 Gy were applied preoperatively, followed by adjuvant
      chemotherapy. The operation comprised total mesorectal excision of the lower two
      thirds of the rectum. Calcium folinate and 5-fluoroucil were administered in six
      chemotherapy cycles. Primarily inoperable patients received preoperative
      irradiation with up to 50.4 Gy in both periods to attain down-staging. The
      following surgical procedures were applied: abdominal perineal extirpations, deep
      anterior resections, coloanal anastomoses, colon pouch anal anastomoses and
      transanal microsurgical resections. RESULTS: In 469 curatively operated patients,
      including primarily inoperable patients after down-staging radiotherapy, the
      rates of local recurrence were 5.8% with a mean follow-up observation of 4.29
      years, and the carcinoma-specific 4-year actuarial survival was 84%. The rate of
      recurrence was highest in the lowest segment level of the rectum (7.6 as compared
      to 2.4%, P = 0.042). The rates of local recurrence were 7.4% in period I and 4.3%
      in period II (P = 0.44). The carcinoma-specific 4-year actuarial survivals were
      81% in period I and 87% in period II (P = 0.202). Investigation of the subgroups
      of irradiated patients showed complete freedom from recurrence after a mean
      follow-up observation time of 3.58 years for patients in stage uT3 with total
      mesorectal excision, preoperative radiotherapy and postoperative chemotherapy (n
      = 51). The difference from patients without postoperative chemotherapy was
      significant (P = 0.018). After radiotherapy, the complication observed was a
      raised rate of sacral cavity infections after total resection of the rectum (p =
      0.039). CONCLUSION: Total mesorectal excision, preoperative radiotherapy and
      postoperative chemotherapy can effectively influence the rate of local
      recurrences after rectal carcinoma operations (0-4.3% after a mean period of
      follow-up observation of 3.58 years). No appraisal can be made with regard to the
      benefit resulting from the individual measures.

PMID- 11963500
TI  - [Immune tolerance and active suppression in oncology. Immunological principles
      and therapeutic options].
AB  - In view of the fact that conventional therapies continue to yield unsatisfactory
      results, a therapy based on tumor immunology is of increasing interest. The
      results of some clinical immunotherapy studies have shown that the mechanism of
      tolerance induced by tumors is of critical importance. There are several
      mechanisms to be recognized by the tumor, such asanergy, immunosuppressive
      cytokines, immunodeviation and dysfunction of the T-lymphocytes. The so-called
      tumor escape mechanisms, which often refer to molecules that contribute to the
      recognition of antigens and activation of specific T cells, also lead to
      immunological tolerance. Immunotherapies based on gene-modified tumor cells,
      peptide-pulsed antigen presenting cells (APC) or antibody therapies to activate
      immune cells, have a fairly reasonable chance of being successful if
      immunological tolerance can be understood and influenced. Time will show if
      combining all sorts of immunotherapy that are based on different strategies, can
      induce tumor rejection more efficiently. In the scope of multimodal therapy
      concepts, immunotherapy only seems to be reasonable if the immunological
      tolerance that was induced by tumors can be overcome. Immunological markers are
      of crucial importance, not only for the therapy but also for the diagnosis and
      prognosis of cancer patients.

PMID- 11963501
TI  - [Effect of thoracic epidural analgesia on the early postoperative phase after
      interventions on the gastrointestinal tract].
AB  - INTRODUCTION: Thoracic epidural anesthesia is increasingly being used in visceral
      surgery as an adjuvant to general anesthesia and, in addition, as a postoperative
      method of thoracic epidural analgesia (TEA). This method interrupts specifically
      nociceptive reflexes, increases the blood supply by blocking sympathetic
      activation, improves pulmonary function, and has a beneficial effect on
      gastrointestinal (GI) motility. METHODS: A retrospective study was conducted on
      175 patients with a primary GI carcinoma operated between January 1, 1999 and
      December 31, 1999; 78 operations were performed on the upper GI tract (UGI,
      gastrectomy), and 97 on the lower GI tract (LGI, anterior rectum resection). The
      postoperative course in patients with and without TEA was compared. For
      intraoperative and postoperative catheter analgesia, bupivacaine (intraoperative:
      0.25%; postoperative: 0.125%) and fentanyl were used. General anesthesia was
      administered as balanced anesthesia. RESULTS: A total of 102 patients received
      combined anesthesia with TEA (UGI n = 61/LGI n = 41) and 73 patients were given
      general anesthesia with continuous postoperative, intravenous pain therapy or a
      patient-controlled analgesia (PCA) pump (UGI n = 17/LGI n = 56). There was no
      difference between the groups with and without TEA in terms of initial
      demographic details, such as age distribution, tumor stage or ASA classification.
      Under TEA, the length of stay in the intensive care unit (P < 0.01), the
      administration of antibiotics (P < 0.001), days without oral nutrition (p < 0.05)
      and the rate of anastomosis insufficiencies (P < 0.001) was significantly reduced
      after operations on the upper GI tract. After surgery on the lower GI tract, the
      use of TEA led to less frequent vomiting and earlier resumption of GI motility (P
      < 0.01). However, these positive effects did not have a significant beneficial
      impact on overall hospitalization. CONCLUSION: The combination of TEA and general
      anesthesia has been shown to offer advantages after operations on both the upper
      and the lower GI tract. The positive effects of the TEA in the postoperative
      period should be used for the early enteric nutrition and mobilization of
      patients.

PMID- 11963502
TI  - [Doppler ultrasound assisted hemorrhoid artery ligation. A new therapy in
      symptomatic hemorrhoids].
AB  - In 1995, Morinaga et al. (Japan) reported on a new technique in the treatment of
      hemorrhoids. We report the results of our first 105 patients thus treated. By a
      specially designed proctoscope coupled with a Doppler transducer, the
      hemorrhoidal arteries are looked for and ligated. All stages of hemorrhoid were
      treated. This method is painless, successful, and has a low rate of
      complications. It is for outpatients and is an alternative to all other methods
      in the treatment of hemorrhoids.

PMID- 11963503
TI  - [Experiences with ambulatory arteriovenous shunt surgery. A cost-benefit
      analysis].
AB  - Placement of arteriovenous (av) fistulas has been executed at the reporting
      surgical department for 3 years. Calculation of the reimbursement by the
      insurance companies is based on the so-called "Unique Evaluation Table"
      (Einheitlicher Bewertungsmassstab). The aim of the study was to evaluate the
      efficiency of the placement of av fistulas in an out-patient setting and the
      acceptance of this approach in the patients. The costs based on an average of the
      duration of the intervention and treatment at the out-patient clinic per time
      unit for surgeon, nurse and operating room, as well as costs for use of specific
      materials were listed, summarized, and compared with the amount of money which
      was reimbursed by the insurance companies according to the "Unique Evaluation
      Table". During the 3-year time period, 67 patients underwent 70 placements of av
      fistulas in an out-patient setting (in total, 532 interventions). Patients
      answered a questionnaire, and procedures were evaluated for average costs. Based
      on the table-dependent reimbursement of DM 274.00 (according to the "Unique
      Evaluation Table"), costs of DM 497.94 (DM 445.50 for 54 min of mean duration of
      surgical procedure plus DM 52.44 for materials) were determined, indicating that
      no full reimbursement was found despite the fact that there was only a minimal
      rate of early complications (thrombosis, n = 2 [3%]) (infection, n = 1 [1.5%]).
      The expenses were 81.7% on average above the level of the reimbursement. In
      conclusion, despite high acceptance of an out-patient setting for placement of av
      fistulas in patients (82%), it is not efficient from an economic point of view
      and can be only provided for specifically selected cases. Therefore, it is not
      advisable at present to place av fistulas at German out-patient clinics with no
      following admission of the patients, to avoid financial disadvantages for the
      surgical department. New negotiations between the medical profession and the
      insurance companies are urgently needed to ensure an improved financial outcome
      for the clinics.

PMID- 11963504
TI  - [Primary glomangioma of the liver. A new differential benign liver tumor
      diagnosis].
AB  - Glomus organs are arteriovenous anastomoses which control the thermoregulation of
      the extremities. Benign tumors of these glomus organs, termed "glomangiomas", are
      therefore most frequently located in the fingers and toes. Case reports of
      primary glomangiomas in the respiratory- and gastrointestinal tracts as well as
      in the genital organs have been published. On the other hand, glomus tumors of
      the liver have not yet been described. We report the case of a 61-year-old
      patient with a smooth subcapsular lesion within the liver detected by a routine
      ultrasound scan. Further diagnostic imaging did not match with one of the common
      liver tumors. The diagnosis of a glomangioma was finally made by liver biopsy and
      subsequent histology. A review of the literature revealed a potential
      transformation of glomangiomas. Since the patient reported on inappetence weight
      loss and the tumor showed growth tendency, the indication for surgical excision
      was made. Final histologic investigation revealed no signs of malignancy. The
      primary glomangioma of the liver is a new differential diagnosis of benign liver
      tumors. As there is a possibility of malignant degeneration, we propose the
      decision for surgical removal once there are clinical symptoms and a growth
      tendency of the lesion.

PMID- 11963505
TI  - [Leiomyosarcoma of the hernial sac in inguinal hernia].
AB  - Malignant tumors associated with hernial sacs are rare entities. A review of
      literature offers only small groups of patients. The high incidence of inguinal
      hernia repair operations demands recognition of this morbidity. It should be
      suspected in cases of tight tissue in the hernial sac in differentiation to the
      unreduced inguinal and femoral hernia. Therapy of choice must be a resection in
      toto (R0), incomplete resection causes inguinal spreading or recurrence of the
      tumor. The exact evaluation of the surroundings should follow. There is no other
      standardized therapy besides operation. A case of leiomyosarcoma in inguinal
      hernia will present the entity of neoplastic disease in hernial sac.

PMID- 11963506
TI  - [Comment on C. Heitmann et al.: Surgical concept and outcome in necrotizing
      fasciitis].

PMID- 11963508
TI  - [Leadership Seminar for Clinic Physicians].

PMID- 11963507
TI  - [Comment on Ch. Bonner et al.: Fournier gangrene as a rare complication after
      stapler hemorrhoidectomy].

PMID- 11963509
TI  - [DRG practice].

PMID- 11963510
TI  - [Insurance claim fraud--personal disclosure?].

PMID- 11963511
TI  - [Reuse of disposable articles--current problems].

PMID- 11963512
TI  - The Third Amyot Lecture. How science informs the decisions of government.

PMID- 11963514
TI  - Impact of vaccine cost and information about complications of varicella on
      parental decision regarding varicella vaccine.
AB  - BACKGROUND: The influence of providing information about complications of disease
      and vaccine cost on parental decision to vaccinate against varicella was
      assessed. METHOD: During telephone interviews of 330 parents of infants aged 9
      months, parents were asked if they would agree to have their child vaccinated and
      were presented information first about varicella complications and then about
      cost of the vaccine. RESULTS: When complications were explained but information
      about cost was not, 94% of parents were favourable toward having their child
      vaccinated. When complications were not explained but cost was presented, this
      percentage was only 34%. When both cost and complications were presented, 60% of
      parents were favourable toward the vaccine. INTERPRETATION: In improving
      receptivity towards varicella vaccine, parents should always be presented data
      regarding varicella complications by their health care provider.

PMID- 11963513
TI  - Refusals and delay of immunization within southwest Alberta. Understanding
      alternative beliefs and religious perspectives.
AB  - BACKGROUND: Immunization is a necessary component of well child services within
      public health. Despite the documented effectiveness of vaccines, some parents
      choose to refuse or delay immunization for their children. Adherence to different
      beliefs has affected immunization coverage in one Regional Health Authority in
      Southwest Alberta. METHODS: This qualitative study involved exploratory,
      descriptive open-ended interviews with a sample of 47. The sample included people
      of Dutch ethnic background, Hutterites, and parents and practitioners who engage
      in alternative health beliefs and practices. RESULTS: Major findings include: 1)
      among the Dutch, most noted their decision to refuse to immunize was based on
      religious beliefs; 2) the Hutterites' decision not to immunize was due to their
      experiences with adverse reactions but was further supported by their use of
      alternative health; and, 3) the alternative health group are more concerned with
      the safety of vaccines with regard to the short- and long-term effects on their
      children's health. DISCUSSION: All three groups conveyed a common concern of
      child health and safety. Educational initiatives need to be implemented to allay
      parents' fears. Community development activities with individuals of the groups
      included here who support immunization will increase acceptance of immunization.

PMID- 11963515
TI  - The impact of policy changes on the health of recent immigrants and refugees in
      the inner city. A qualitative study of service providers' perspectives.
AB  - BACKGROUND: Dramatic changes to health and social policy have taken place in
      Ontario over the last five years with few attempts to measure their impact on
      health outcomes. This study explored service providers' opinions about the impact
      of four major policy changes on the health of recent immigrant and refugee
      communities in Toronto's inner city. METHODS: Semi-structured key informant
      interviews. RESULTS: Reductions in funding for welfare, hospitals and community
      agencies were seen to have had major effects on the health of newcomers. Emergent
      themes included erosion of the social determinants of health, reduced access to
      health care, increased need for advocacy, deterioration in mental health, and an
      increase in wife abuse. CONCLUSIONS: Several areas were identified where policy
      changes were perceived to have had a negative impact on the health of recent
      immigrants and refugees. This study provides insights for policy-makers, inner
      city planners and researchers conducting population-based studies of immigrant
      health.

PMID- 11963516
TI  - Viral hepatitis in a Canadian street-involved population.
AB  - BACKGROUND: Data on the prevalence and compliance with management of viral
      hepatitis in the street-involved population are limited. METHOD: Hepatitis A
      (HAV), B (HBV) and C (HCV) serology and compliance with HBV vaccination were
      documented in 533 street-involved individuals. RESULTS: The mean age of the study
      population was 25.7 years (range: 11-65) and 53% were female. Serologic evidence
      of HAV infection was present in 53%; HBV, 12% (3% ongoing infection); and HCV,
      17%. HAV infections were associated with Aboriginal/Metis ethnicity and age over
      25 years; HBV with injection drug use (IDU); and HCV with IDU, sex trade work and
      age over 25 years. Compliance with three-step HBV vaccination was 98%, 77% and
      63%. CONCLUSIONS: HAV, HBV and HCV are common infections in urban street-involved
      persons. Successful HBV (and presumably HAV) vaccination can be achieved in the
      majority of this population, but concerns exist regarding compliance with more
      long-term, parenterally-based antiviral therapies.

PMID- 11963517
TI  - Factors affecting the uptake of community recreation as health promotion for
      women on low incomes.
AB  - BACKGROUND: There have been repeated calls for research on the factors that
      promote the spread of successful local health promotion initiatives from one
      community to another. We examined the factors that affected the uptake of an
      initiative designed in one community to improve the health of women living below
      the poverty line through increased access to community recreation. METHODS:
      Workshops were held in three other communities and uptake efforts were tracked
      for one year through follow-up site visits and telephone interviews with workshop
      participants. RESULTS: Making the issue a priority, actively involving the women
      in planning, pooling resources, sharing responsibility through partnerships, and
      addressing the structural dimensions of poverty were factors that enabled uptake.
      Factors that inhibited uptake included an emphasis on revenue generation,
      professionally led planning, inadequate attention to structural barriers, the
      undervaluing of certain resources, and an over-reliance on one idea champion.
      CONCLUSION: A shift in how municipal recreation departments view their role as
      partners in community health promotion is required if programs are to promote
      health and be accessible to under-served populations.

PMID- 11963518
TI  - [Social inequalities in health. A partnership of research and education].
AB  - The Chair on Health Inequality is one of the 12 Chairs created by the CHSRF.
      Resulting from a partnership between l'Universite de Montreal, together with the
      Direction de la sante publique of the Regie regionale de la sante et des services
      sociaux Montreal-centre, the Chair will create a research program that will
      document and assess the role of public health programs based on social
      development in urban districts, in reducing social health inequality. This
      research infrastructure will support two training programs: 1) a post-doctoral
      training program that will introduce newly minted social science PhDs to
      collaborative research in public health; and 2) a professional doctorate program
      for public health professionals. The decision-makers and policy-makers targeted
      by the Chair's knowledge diffusion program are Directors of public health
      organizations.

PMID- 11963519
TI  - An examination of cancer risk beliefs among adults from Toronto's Somali,
      Chinese, Russian and Spanish-speaking communities.
AB  - BACKGROUND: Canada's growing ethnocultural diversity challenges health
      professionals to develop culturally sensitive cancer prevention strategies.
      Little is known about the ethnocultural specificity of cancer risk beliefs. This
      qualitative pilot study examined cancer risk beliefs, focusing on diet, among
      adults from Toronto's Somali, Chinese, Russian, and Spanish-speaking communities.
      METHOD: Group interviews (n = 4) were conducted with convenience samples of
      adults (total n = 45) from four ethnocultural communities (total 45
      participants). RESULTS: The constant comparison method of data analysis
      identified three common themes: knowledge of cancer risk factors, concern about
      the food supply, and the roles of spiritual and emotional well-being. Two areas
      of contrasting belief concerning specific mediators of cancer risk were
      identified. INTERPRETATION: Findings support the investigation of cultural
      specific health promotion strategies emphasizing both the maintenance of
      traditional cancer protective eating practices and the adoption of additional
      healthy eating practices among new Canadians. More research is needed to enhance
      our understanding of ethnoculturally specific cancer risk beliefs and practices
      to ensure the cultural relevance of programming.

PMID- 11963521
TI  - Sun protection among parents and children at freshwater beaches.
AB  - OBJECTIVES: This paper describes the sun-related behaviour of parents and their
      children, ages 5-12 years. METHODS: In-person interviews were conducted with
      parents and observations of parents and their children to ascertain: 1) parents'
      self-reported use of sunscreen, 2) parent-proxy reports of children's sunscreen
      use, and 3) observations of parents' and children's use of shade, hats and
      protective clothing. Data collection took place at freshwater beaches in BC's
      Southern Interior, between 12 pm and 5 pm, over a seven-day period during August
      1999. RESULTS: 94 parents were interviewed and observed. Parent-proxy reports and
      observational data were collected on 161 children. Half (53%) of parents reported
      they were wearing sunscreen at the time of the on-beach interview. Most (65%) of
      parents reported that their children were wearing sunscreen at the time of the on
      beach interview. Children's first application of sunscreen took place on average
      1.5 hours prior to interview. Most parents (86%) reported that their children's
      sunscreen had not been reapplied at the time of interview. Few parents (13%) or
      children (5%) used shade as provided by nearby trees or umbrellas. CONCLUSION:
      Public education should emphasize sunscreen re-application. Actions should be
      taken to enhance the convenient use of shade structures at public beaches.

PMID- 11963520
TI  - A retrospective study of the accuracy of cancer information in Ontario daily
      newspapers.
AB  - CONTEXT: Studies suggest that the mass media is a common source of cancer
      information for the public. However, the quality of cancer information through
      various print outlets has not been extensively investigated. OBJECTIVES: To
      assess the accuracy of cancer information in a retrospective sample of Ontario
      daily newspapers as well as to determine the amount of mobilizing (enabling)
      information about community resources for cancer. METHODS AND RESULTS: Of 1,027
      articles on cancer for 1991, drawn from the 5 highest and 5 lowest circulating
      newspapers, a random 30% sample (306 articles) was obtained. Only 40 articles had
      traceable citations (journal name, name of researcher, name of educational
      institution, or direct quotes from identifiable sources). Of these, 47.5% had
      misleading titles and 55% included erroneous information or omitted important
      study results. Only 13 (6.9%) included mobilizing information regarding
      prevention, diagnosis, treatment or support. INTERPRETATION: Cancer information
      in newspapers contain frequent inaccuracies and fail to provide mobilizing
      information. Inaccurate newspaper information about cancer is of concern if the
      public relies on this channel for at least part of their health knowledge.

PMID- 11963522
TI  - Identifying the needs of Innu and Inuit patients in urban health settings in
      Newfoundland and Labrador.
AB  - BACKGROUND: Labrador's Innu and Inuit live in nine small, isolated villages, and
      must travel to the urban centres of Goose Bay, Labrador and/or St. John's,
      Newfoundland for most health services. This study responds to anecdotal evidence
      of Aboriginal dissatisfaction with these services from the St. John's Native
      Friendship Centre Association (SJNFCA); it describes Aboriginal experiences and
      identifies relevant needs. METHODS: The study consisted of qualitative interviews
      (N = 143), conducted by trained local researchers, and nine focus groups. The
      interviews were narrative-based, appropriate to the Aboriginal culture of
      participants. Participants were recruited from the client list of the SJNFCA.
      FINDINGS: Almost all study participants experience significant difficulties
      including profound disorientation, language and communication difficulties,
      inadequate accommodations, and altered diets. Cross-cultural relations are
      particularly problematic for the Innu. CONCLUSIONS: These findings, and 19
      recommendations made to the provincial government (8 main recommendations appear
      in Table II), could lead to improved services for Innu and Inuit using urban
      health services. Workshops in development could mean more awareness among health
      care practitioners.

PMID- 11963523
TI  - Home visitation programs for at-risk young families. A systematic literature
      review.
AB  - BACKGROUND: This systematic literature review is stimulated by the perceived need
      of investigator, practice and policy stakeholders for a complete but parsimonious
      summary of key elements of programs that use home visitation for at-risk young
      families as the major delivery method. OBJECTIVES: To describe the program
      components, practices, outcomes, and reliability of the evaluation approaches.
      METHODS: Computer and hand searches of literature were carried out. Reports of
      established programs, from the last five years, that describe home visitation
      services to at-risk families were included. A comprehensive data collection tool
      was used in the analysis of the findings. FINDINGS: Improvements over the
      previous five years were seen in the following areas: use of early intervention
      model, inclusion of comparison groups and adequate sampling. DISCUSSION:
      Challenges remain in development, targeting and reporting of home visitation
      practice, overall lack of impact, differential effects by program site, retention
      of participants and appropriate measurement.

PMID- 11963524
TI  - Examining scope, strategies and resources: adolescents and environmental tobacco
      smoke.

PMID- 11963525
TI  - Tuberculosis in immigrants to Canada. A global problem which requires a global
      solution.

PMID- 11963526
TI  - Effectiveness of the Immigration Medical Surveillance Program for tuberculosis in
      Ontario.
AB  - BACKGROUND: Citizenship and Immigration Canada (CIC) screens immigrants for TB
      and permits those with inactive pulmonary TB to enter Canada conditionally,
      subject to medical surveillance; we studied this program in Ontario. METHOD: This
      was an administrative database study with linkage of national and provincial
      data. RESULTS: In 1994-95, 1,341 cases of foreign-born active TB were diagnosed
      and a CIC record was found for 1,095. 149 (14%) were classified for surveillance
      and 142 were included in the analysis. A significant proportion (39/142: 27%)
      were diagnosed either before or as a result of immigration screening in Canada.
      These persons had arrived as visitors or refugees and were excluded from further
      analysis. Only 21 of the remaining 103 persons (20%) with immigration screening
      before the diagnosis of TB adhered to surveillance. Only 1 of 16 (6%) eligible
      persons was given therapy to prevent future episodes of active TB. Most presented
      with symptoms (82/103:82%) suggesting potential for TB transmission in Ontario.
      INTERPRETATION: The current TB surveillance system for high-risk immigrants to
      Ontario is not effective in identifying and treating latent infection, and thus
      not effective in preventing future cases.

PMID- 11963527
TI  - [Factors related to non-compliance with active tuberculosis treatment in Montreal
      1992-1995].
AB  - OBJECTIVE: To determine the extent of non-compliance with antituberculosis
      treatment in Montreal and whether it is influenced by the characteristics of the
      health care setting. METHODS: Retrospective medical and public health chart
      review of tuberculosis patients reported to the Montreal-Centre Department of
      Public Health between 1992-1995. A non-compliant patient is defined as one who
      has taken less than 80% of prescribed antituberculosis medication. RESULTS: Among
      patients for whom the compliance status was available, 19.8% were non-compliant.
      In univariate analysis, risk factors significantly associated with non-compliance
      included: living alone, birth in an endemic country for tuberculosis, side
      effects related to the medication, and follow-up in a clinic not specialized for
      tuberculosis. In multivariate analysis, increase of age by one unit (OR: 1.1; 95%
      CI: 1.02-1.1), and risk factors such as alcoholism (OR: 33.8; 95% CI: 5.8-194.4)
      and being HIV positive (OR: 8.9; 95% CI: 2.9-26.6) were independently associated
      with non-compliance. CONCLUSION: Non-observance seemed to be associated with
      patients' characteristics rather than health care system characteristics.

PMID- 11963528
TI  - Is public health ethical?

PMID- 11963529
TI  - [Globalization and public health. Doha: a reversal?].

PMID- 11963530
TI  - [Knowledge and attitudes of prison staff towards HIV/AIDS: a European study].
AB  - The goal of this European pilot study was to evaluate the knowledge, attitudes
      and beliefs of prison staff from five countries towards HIV infection and to
      identify factors related to the potential discrimination of HIV-positive inmates.
      The survey revealed that the levels of knowledge with regard to HIV transmission
      and the degrees of tolerance varied significantly between prisons. A large
      proportion of staff overestimated the prevalence of HIV in their prison and
      feared being contaminated. The willingness of the staff to know the inmates' HIV
      seropositive status was negatively correlated to their level of tolerance;
      however, it was positively correlated to their knowledge of the modes of HIV
      transmission. This study underlines the necessity to improve HIV/AIDS prevention
      policy for prison staff in order to strengthen good practice in terms of managing
      the risk of contamination and hindering discrimination.

PMID- 11963531
TI  - [Study of terminally ill patients' needs in an university hospital].
AB  - Within the framework of a project to create a Mobile Palliative Care Unit, in May
      2000 we conducted an evaluation of the needs of patients undergoing palliative
      care in a university hospital centre. Thanks to the use of a standardised
      questionnaire, a team of doctors and nurses for each service was able to describe
      the symptoms, treatments and social and family situations as well as assess the
      eventual outcome of the patients hospitalised in their service who were in an
      advanced or terminal phase. In total, the study included 52 cases (5.5% of
      available beds). 81% of patients reported suffering from physical discomfort and
      70% from psychological distress. A specific treatment for the disease in question
      was maintained in 28% of the cases. In 24% of the cases, the patient had social
      problems. Among all of the patients, 31% were on the waiting list to be
      transferred to a different location.

PMID- 11963533
TI  - [Epidemiology of low birth weight in Tunisia].
AB  - Our study aims to assess the determinants and the frequency of low birth weight
      (LBW) in the health district of Monastir (Tunisia). The study was carried out
      over a three-year period, beginning in January 1995 and ending in December 1997.
      According to the Monastir district's childbirth register, 1,194 of the 21,393
      newborns delivered were babies born with a low birth weight (LBW rate of 5.6%).
      Common characteristics among the LBW infants were the following: females are more
      often affected than males (sex ratio of 1.25); 22% of cases were twins; one-third
      were premature births (< 37 weeks). This study of the determinants of LBW
      demonstrates that there are several factors linked to the occurrence of LBW such
      as the mother's age, the number of times she has given birth, an interval between
      pregnancies of less than 24 months, lack of prenatal care, and the female sex of
      the baby.

PMID- 11963532
TI  - [Evaluation of a new form of care: the permanently maintained health care
      facility at the university hospital center in Nantes].
AB  - Considering the consequences of social instability within the health care system
      has become a public health priority. Each public hospital center in France is
      obliged to create a unit for welcoming impoverished and vulnerable people
      (Permanently Maintained Health Care Facilities). The university hospital in
      Nantes opened a socio-medical out-patient consultation service in November 1999
      with the main objective being to bring these patients back into the usual
      ambulatory care system. The evaluation of the first few months of its operation
      reveals that one out of every two patients is a young person with a low-income
      and without any social protection. The possibilities of reorientation towards the
      regular care system are discussed.

PMID- 11963534
TI  - [Perceived health survey of 3,800 French adolescents: methodological aspects].
AB  - An epidemiological survey was carried out by a local association network and was
      developed in partnership with regional and national institutions. The survey on
      well-being and health was conducted over an 18-month period in the French
      department of Charente. The purpose of the research was to test the hypothesis
      that "the change in context that is experienced by adolescents at the end of
      junior high school and at the beginning of high school leads to an increase in
      risky behaviours". To this end, the survey questioned 3,800 young people on a
      random basis, mixing those from different grades, those participating in
      vocational training and apprenticeships, and those from public and private
      schools. The accomplishment of this survey was made possible thanks to the
      motivation of a pre-existing strong local network organised and linked to
      education professionals, the technical contribution of the region's health
      observatory who conducted the statistical analysis of the data, and the
      assistance of Unit 472 of the French Institute of Health and Medical Research who
      provided scientific supervision and advice. The high participation rate and
      quality of the data (comparable with and even better than some existing studies)
      demonstrate that it is possible for local associations to carry out effective
      epidemiological surveys based on the needs keenly felt by the workers themselves,
      within the scope of a reasonable budget and in a short time span without
      sacrificing the precision demanded by the scientific method.

PMID- 11963535
TI  - [A qualitative approach to the awareness of occupational risk in adolescents].
AB  - In terms of health promotion, the individual's awareness of risk is the first
      step towards the adoption of preventive behaviours. Our study intended to
      evaluate, through conducting semi-directed interviews, the awareness of
      occupational risk in adolescents completing their formal professional training.
      Students studying to become bakers or hairstylists as well as those working in
      wood craftsmanship did not identify their respective professions as being at risk
      of leading to a work-related accident or illness. This awareness is not strongly
      encouraged at the time of academic training and therefore the student has very
      little opportunity to be advised regarding the preventive measures that he/she
      should adopt; whereas, for this particular public, their health is already not a
      priority concern.

PMID- 11963537
TI  - [Smoking prevention in France from 1997 to 1999].
AB  - The years following the adoption of the Veil law (passed in 1977) were not
      characterised by substantial results in terms of a reduction in tobacco
      consumption. In 1991, the Evin law marked an important step in the regeneration
      and structuring of the fight against this substance. It is within this see-sawing
      context of smoking behaviour that a three-year (1997-1999) plan was supported and
      implemented by the French National Social Security and the French Committee for
      Health Education. The central theme was to help people to quit. During this same
      time period, the consensus conference (1997) as well as the announcement of a
      governmental plan (1999) came about to consolidate and magnify these directions.
      The observance of the change in tobacco consumption permits one to acknowledge
      that the Evin law and its measures for assistance had a positive impact during
      the early 1990s. On the other hand, this impact seems to have been on the whole
      "blunted" throughout the second half of the decade. The main hypothesis to
      explain this stagnation is that the increase in the price of tobacco was less
      sensitive and that the measures aimed at enforcing this law were less often
      applied, whereas at the very same time the commitment of the actors involved in
      the fight against smoking was strong. This assessment permits one to: 1) confirm
      the fact that in public health, health promotion actions are effective when they
      are jointly associated with initiatives that are coercive (the law and its
      application) and educational, the development of the environment and the
      improvement of care; and 2) remember the importance of truly applying the clauses
      of the Evin law and perhaps eventually adding to them.

PMID- 11963536
TI  - [Children's medical records, HIV and confidentiality: practices and attitudes of
      physicians and families].
AB  - The aim of this study is to describe the attitudes and practices of doctors and
      families regarding the use of the individual child health journal, especially by
      exploring the contradictions between the validity and confidentiality of its
      content, in particular with respect to HIV infection. In order to accomplish
      this, both doctors (N = 380) and families (N = 242) were questioned, most of them
      living and working in Seine-Saint-Denis, the metropolitan district with the third
      highest prevalence rate of HIV. The findings indicate that: most families are not
      always prepared to make sure that the confidential use of the child's health
      journal is maintained, and even less so those affected by HIV; doctors refrain
      from recording certain psychological and even medical data in the child health
      journal for fear of the information's misuse within the social sphere; doctors as
      well as families expressed their preoccupations concerning the confidentiality of
      the child health journal, essentially with respect to its content and how it is
      used in various contexts. A number of possibilities are proposed by the study's
      participants: establish a vaccination record separate from the child health
      journal, educate parents on how to maintain its confidential use and train the
      health workers to this end.

PMID- 11963538
TI  - [Induction of invasion and epithelial tubulogenesis in primary human keratinocyte
      culture].
AB  - In this study we used invasion and tubulogenesis assays to measure the
      morphogenetic potential of primary human keratinocytes in vitro. We also used
      human embryonic and dermal fibroblasts in coculture with keratinocytes and
      compared their influence on keratinocyte behavior in these different cell culture
      systems. The keratinocytes retained morphogenetic potential in vitro. In the
      presence of embryonic fibroblasts, the keratinocytes formed tubes and invaded
      collagen gel. A three-dimensional architecture of invasion clusters was
      reconstructed. We conclude that the cellular mechanisms of invasion and
      tubulogenesis are similar.

PMID- 11963539
TI  - [Phorbol-12-myristate-13-acetate prevents the inhibitory effect of A23187 on
      erythroid differentiation of K562 cells induced by dimethylsulfoxide].
AB  - The differentiating effect of DMSO on K562 cells was studied against the
      background of pretreatment of the cells by the modulators of activities of
      protein kinase C and Ca signaling, phorbol 12-myristate 13-acetate, and ionophore
      A23187. The 2-hour pretreatment of K562 cells with A23187 (1 microM), rather than
      phorbol 12-myristate 13-acetate (0.1 microM), led to inhibition of the
      differentiating effect of DMSO (0.1%) during the subsequent four days of
      incubation. When the cells were pretreated jointly with A23187 and phorbol 12
      myristate 13-acetate, the DMSO-induced erythroid differentiation was restored.
      Analysis of the DNA-degrading effect of the reagents used on K562 cells by
      fluorescent dyes under the same conditions suggests that this activity is induced
      in the presence of DMSO in the cells pretreated with a combination of phorbol 12
      myristate 13-acetate and A23187 or without pretreatment.

PMID- 11963540
TI  - [Enzymatic system of metabolism and detoxication of xenobiotics as a basis for
      metabolic profiling in prognosis of risk of the pathological processes].
AB  - We studied intraspecific features of the main enzymes of metabolism and
      detoxication of xenobiotics on mice (eight inbred lines) and rats (five lines)
      for estimation of possible variants of complete or incomplete metabolic equality.
      Significant genetically determined intraspecific differences for activities of
      the enzymes of metabolism and detoxication of xenobiotics were described.
      Generalized criteria for comparison of the metabolic status were proposed on the
      basis of activities of the main enzymes: cytochrome P-450 (hydroxylation and
      epoxidation), epoxyhydrolase, glutathione-S-transferase, UDP-glucuronosyl
      transferase, and sulfotransferase. The proposed criteria for estimation of the
      metabolic parameters of an individual can serve as a basis of metabolic
      portraiting.

PMID- 11963543
TI  - [Inhibition of IAA-induced growth of wheat coleoptile fragments by chitin
      chitosan oligomers].
AB  - We studied the comparative effects of the phytohormone indolylacetic acid (IAA)
      and chitooligosaccharides (5-10 kDa, degree of deacetylation 35%) on the growth
      of coleoptile fragments of 3-day wheat germlings. IAA (10 mg/l) stimulated
      elongation of coleoptile fragments by 80%, as compared to the control (water).
      Chitooligosaccharides at 0.01-1500 mg/l or higher did not exert auxin-like
      effects, but at 100 mg/l or higher, suppressed elongation of the coleoptile
      fragments, as compared to the control (water). Incubation of coleoptile fragments
      in solutions containing both IAA and chitooligosaccharides (100 mg/l or higher)
      suppressed their IAA-induced elongation, which correlated with the inhibition of
      growth of 3-day wheat germlings after wetting seeds in solutions of
      chitooligosaccharides. It has been proposed that the phytohormone-like properties
      of chitooligosaccharides can be related to changes in the endogenous balance of
      phytohormones in plants.

PMID- 11963542
TI  - [Nonexponential diffusion extinction of spin echo from water protons in wheat
      root].
AB  - The method of NMR spin echo with the magnetic field pulse gradient was used for
      studying self-diffusion of water molecules in the radial root direction. It was
      shown on the basis of physiologopharmacological methods of modification of the
      object that the coefficients of water self-diffusion resulting from computer
      decomposition of nonexponential diffusion extinction of the relative echo
      amplitude in the root to components are related to the subcellular and
      supercellular organization (structure) of the root and reflect changes in water
      permeability of the two transport channels of plasmodesmas.

PMID- 11963541
TI  - [Comparative study of cytotoxic and hemolytic effects of triterpenoids isolated
      from Ginseng and Sea cucumber].
AB  - Specific features of cytotoxic (against tumor cells), hemolytic, and liposomal
      (effect on permeability) activities of triterpenoids isolated from sea cucumbers
      and ginseng roots were studied. It was shown that oleanolic acid,
      protopanaxatriol, and protopanaxadiol at 5 to 20 micrograms/ml inhibited the
      growth of tumor cells, while at doses up to 100 micrograms/ml, they did not
      induce hemolysis or changes in liposome permeability. Monoglucosides of
      protopanaxadiol, Rh2, Rg3, and substance K exerted moderate cytotoxic and
      membrane activities. The membrane sensitivity to these glucosides was inversely
      proportional to the membrane content of cholesterol. The cytotoxicity of the
      protopanaxadiol-active glycosides increased with a decrease of pH of the medium.
      All studied glycosides did not affect the cell and model lipid membranes. The
      activity of the oleanolic acid glycoside, ginsenoside Z-R1, depended to a great
      extent on the pH of the medium. The decrease of pH from 7.4 to 5.6 increased the
      membranolytic activities by more than one order of magnitude. Glycosides from sea
      cucumbers, echinosides A and B, holothurins A and B, holotoxin A1, and
      cucumarioside G1, had very high cytotoxic and liposomal activities. Addition of
      cholesterol to cell membranes enhanced the cytotoxic effects of these glycosides.
      The ginsenosides with two carbohydrate moieties (bisdesmosides), as well as all
      the panaxatriol glycosides we studied did not exhibit cytotoxic activities
      against tumor cells or alter the permeability of model lipid and lipid-sterol
      membranes. The triterpenoids studied were classified into four categories in
      accordance with their membranotropic activities. A possible protective role of
      these glycosides in the organism-producent is discussed.

PMID- 11963544
TI  - [Once more about hepatoid circumanal glands of dogs. History of their discovery
      and reasons for revision the structural and functional data].
AB  - In the skin surrounding the anus in dogs and other Canidae, there is a glandular
      sheet consisting of strongly developed hepatoid glands, as well as single
      apocrine glands and a certain number of sebaceous glands, which are much smaller
      and occur less frequently than the hepatoid glands. All three circumanal glands
      have excretory ducts connecting with the hair bags (hair funnels). The hepatoid
      glands of some Canidae and Bovidae were extensively studied in the 1920s-1930s,
      but from the beginning of the 1950s until the present, as a result of the often
      repeated mistake passing from one book to another, old information about the
      hepatoid glands was fully lost, while the new information does not answer the
      question about the function of this complex and well developed structure. We were
      successful in repeating the data of the discoverers of the hepatoid glands and
      proved that these glands are exocrine and that their cells excrete protein to
      intercellular channels and then to ducts and hair funnels. According to the
      published data, the odor of the secretory substance of the circumanal hepatoid
      glands is essential for communication in wolves and dogs.

PMID- 11963545
TI  - [Kinetic of beta1-adrenergic reaction of chicken embryo amnion].
AB  - Dose-dependent curves of the inhibitory beta 1-adrenergic reaction of the chick
      embryo amnion were analyzed on the basis of different mathematical models.
      Selection of the optimal model, closest to the experimental data, allows us to
      obtain the reaction parameters with the smallest statistical error. Two main
      characteristics of the physiological reaction, EC50 and Pm, sufficed for the
      description of the action of agonists nonselective for beta 1-adrenoreceptors:
      adrenaline (EC50 0.19 +/- 0.02 microM, Pm 101.3 +/- 1.9%) and salbutamol (EC50
      0.58 +/- 0.01 microM, Pm 42.7 +/- 0.3%). The Hill coefficient n in these
      experiments was close to 1 (1.06 +/- 0.14; 0.96 +/- 0.02). It was necessary to
      introduce fractional values 1 < n < 2 to describe the effects of noradrenaline
      and isopropyl noradrenaline.

PMID- 11963546
TI  - [Dermorphins--a natural opioids with unique primary structure that determines
      their biological specificity].
AB  - Based on the authors' and published data, the spectrum of biological activities
      of dermorphins was theoretically analyzed for the first time from the viewpoint
      of specific structural features of their molecule that determine selective
      affinity to mu-opiate receptors. It was shown that specific distribution of
      dermorphins and corresponding opiate receptors in tissues and organs, especially
      in the CNS structures, determines the role of dermorphins in the regulation of
      functions of the most important physiological systems.

PMID- 11963547
TI  - [Penetration of cow milk angiogenin into the blood after peroral administration
      in mice].
AB  - The cow milk angiogenin consumed by mice perorally penetrated from the
      gastrointestinal tract in the blood flow. In the experimental animals, the blood
      level of exogenous angiogenin first increased to reach a maximum, and then
      gradually decreased to zero. The dynamics of this process depends on the age of
      animals. The data obtained suggest that the cycle of perorally introduced cow
      milk angiogenin in blood is realized in the infantile-juvenile mice at a higher
      rate than in the adult-presenile mice.

PMID- 11963548
TI  - [Effect of lighting oscillations on growth and energetics of the goldfish
      Carassius auratus].
AB  - Periodic oscillations of illumination exert a positive, rather than negative,
      effect on goldfish growth and energetics. In a variable light regime, the fishes
      grow of a higher rate, have decreased oxygen and food requirements, improve the
      utilization of consumed food for growth, and decrease the oxygen expenditure per
      increment of unit body mass. The goldfish reactions to the frequency of
      illumination oscillation and the succession of the stationary light regime by the
      oscillatory regime were described.

PMID- 11963549
TI  - [Characteristics of nitrogen fixation and denitrification in Termites Neotermes
      castaneus, Zootermopsis angusticollis, and Reticulitermes lucifugus].
AB  - We studied specific features of microbial nitrogen fixation and denitrification
      in laboratory cultures of the termites Neotermes castaneus, Zootermopsis
      angusticollis, and Reticulitermes lucifugus, as well as in their nest materials.
      The nitrogenase activity in the termites was much higher than in the materials of
      termitarium. Denitrification was found only in the nest materials of termitarium.
      Studies of the bacterial community of gut nitrogen fixers Neotermes castaneus
      have shown the predominance of anaerobic and facultatively anaerobic bacteria
      that amount to up to 60% of the total number of "gut" bacteria. In the materials
      of termitarium, aerobic cellulose-destroying myxobacteria predominated, which are
      typical inhabitants of plant substrates, a food for the termite.

PMID- 11963550
TI  - [Effects of orthophosphates and condensed phosphates on chemical and spectral
      properties of the humus derivatives of phosphorus and metals].
AB  - Inorganic orthophosphates and condensed phosphates strongly affected the acidic
      basic properties of soil humus substances, which was expressed by the degree of
      their hydrolyzability in alkaline, acidic, and neutral media. The humus
      substances modified by phosphates were characterized by increased electron donor
      (basic, after Lewis) properties, as compared to the native substances, due to
      accumulation of C=C-bonds. They exerted an especially strong dissolving effect on
      Fe- and Al-containing soil minerals and had a greater affinity to exogenous Zn.
      The pattern of distribution of phosphorus in ortho- and pyrophosphates among a
      fraction of humus substances was studied.

PMID- 11963551
TI  - [Evaluation of cell nitrogen and phosphorus quotas in accumulative cultures of
      chlorococcous algae].
AB  - A conceptual model of cell quota was proposed and the parameters were determined
      that characterize the quota dynamics during the development of algae. Based on
      the experimental and empirical-statistical procedures of analysis, the basal
      parameters of cell quotas of nitrogen and phosphorus were obtained for four
      species of chlorococcous algae. The data were also obtained on a variability of
      nitrogen and phosphorus quotas during the development of algae, as well as
      coefficients of excessive accumulation. The phosphorus quota changed within the
      limits of three orders of magnitude and the nitrogen quota, within the limits of
      one order. The highest coefficients of excessive accumulation were 52 and 1.8 for
      phosphorus and nitrogen, respectively.

PMID- 11963552
TI  - [Complementary nuclear DNA in embryo sac cells of Haemanthus albiflos and
      Ornithogalum caudatum].
AB  - Cytophotometric measurements of Feulgen-DNA were carried out in the nuclei of
      embryo sac cells of Haemanthus albiflos and Ornithogalum caudatum. It was found
      that the nuclei of the egg system, haploid in the number of chromosomes, became
      polyploid in DNA amount at the final stages of gametophyte development.

PMID- 11963553
TI  - [Production of interspecies hybrid of cranes by artificial insemination with
      frozen semen].
AB  - Studies of artificial insemination of cranes and cryoconservation of their semen
      have been carried out in the nursery of rare species at the Oka Biosphere Reserve
      for many years. The criterion of successful cryoconservation of the semen is the
      obtaining of fertilized eggs after artificial insemination by the thawed semen.
      An experiment is described on artificial insemination of females of the white
      naped crane Grus vipio by the frozen-thawed semen of the Siberian white crane G.
      leucogeranus after one-year storage of semen in liquid nitrogen. As a result, an
      interspecific hybrid of cranes was obtained, which confirmed the possibility of
      producing a bank of cryoconserved crane semen. The use of the white-naped crane
      females was due to the absence of conspecific males and unavailability of
      Siberian white crane females. Problems of artificial insemination and
      cryoconservation of semen of rare crane species are discussed.

PMID- 11963555
TI  - [Factors affecting the frequency of concealed heterokaryosis in Saccharomyces
      cerevisiae].
AB  - In this work, studies on the phenomenon of concealed heterokaryosis that we
      previously detected in the saccharomycetes yeast strains were continued. New
      approaches to high effectiveness of isolation of cytoductants carrying the
      concealed nucleus were implemented, and the composition of individual concealed
      heterokaryons, zygotic clones, and the first zygotic buds was analyzed by a
      micromanipulator. The relationship between a delay in the growth of the parental
      strain (a potential donor of the concealed nucleus) and a decline in the
      frequency of the appearance of concealed heterokaryons (HKC) was observed. It is
      assumed that different replication rates of two nuclei of the heterokaryon
      probably underlie the appearance of HKC. A drastically decreased level of
      replication of one of the parental nuclei may be connected with the fact that
      binuclear buds appear extremely rarely and give rise to the rapidly "purified"
      progeny consisting of cells carrying the second nucleus with normal replication.
      A lack of the phenotype allows rare binuclear cells to persist as concealed
      heterokaryons. HKC may be detected only when cells of either parental type are
      isolated on the corresponding selective media.

PMID- 11963554
TI  - [ Role of meteorological factors in the formation of the plant nitrate pool].
AB  - Meteorological conditions during the period of plant vegetation make the greatest
      contribution to the formation of the plant nitrate pool. Nitrate nitrogen is
      accumulated at high concentrations during sunless, cold years. The weather
      conditions of the last five to ten days of plant vegetation determine nitrate
      accumulation. The meteorological conditions during the entire period of
      vegetation determine the increase in the content of nitrates due to nitrogen
      fertilizers. The effect of meteorological conditions is especially pronounced in
      low fertility soils and upon introduction of high doses of nitrogen fertilizers.
      The reaction of plants to unfavorable meteorological conditions greatly varies
      with reference to their biological and genotypical specificity.

PMID- 11963556
TI  - [Chimeric yeast prions with unstable inheritance].
AB  - The Saccharomyces cerevisiae [PSI] factor, a cytoplasmic omnipotent nonsense
      suppressor, is a conformationally changed (prion) form of translation termination
      factor eRF3 (Sup35p). Induction and maintenance of the [PSI] factor depend on the
      prionizing peptide located in the N domain of Sup35p. The N domain of Sup35p was
      fused with phosphoribosylaminoimidazole carboxylase (Ade2p), a purine
      biosynthesis enzyme, and the hybrid protein (NM-Sup35p::Ade2p) was tested for
      induction of the [PSI] factor. Transformation with a centromeric plasmid carrying
      the gene for NM-Sup35p::Ade2p induced a [PSI]-like factor in yeast cells, which
      was evident from efficient nonsense suppression. The suppressory effect depended
      on the presence of the prionizing peptide both in the hybrid protein and in
      Sup35p synthesized from the chromosomal gene, as well as on the presence of the
      prion-like [PIN] factor in the cell.

PMID- 11963557
TI  - [Modification of repair DNA synthesis in mutagen-treated human fibroblasts during
      adaptive response and the antimutagenic effect of garlic extract].
AB  - Repair DNA synthesis (RDS) in human fibroblasts during the adaptive responses
      (ARs) induced by cadmium chloride (CdCl2), gamma-radiation, and 4-nitroquinoline
      1-oxide (4NQO) was compared in cells pretreated and not pretreated with garlic
      extract. The RDS was increased during the ARs induced CdCl2 and gamma
      irradiation. Garlic extract stimulated RDS in cells treated by the same mutagens.
      3-Aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) polymerase, decreased
      the RDS rate in cells treated with CdCl2 and gamma-irradiation but had no
      significant effect on cells treated with 4NQO. It was demonstrated that DNA
      repair was involved into cell protection in different ways in the cases of
      antimutagen treatment and AR.

PMID- 11963558
TI  - [Phylogenetic relationships among holarctic populations of Chironomus entis and
      Chironomus plumosus in view of possible horizontal transfer of mitochondrial
      genes].
AB  - In eight Holarctic populations of two typical chironomid sibling species of the
      plumosus group, Chrionomus entis and Chironomus plumosus, nucleotides sequences
      of mitochondrial (cytb) and nuclear (gb2b) gene regions were examined. The
      phylogenetic trees reflecting the evolutionary histories of the nuclear and
      mitochondrial markers exhibited significant differences. On the tree based on the
      nuclear gene sequences the populations clustered according to their species
      affiliation, whereas on the tree based on the mitochondrial gene sequences the
      populations were grouped according to their geographic position. This discrepancy
      is probably explained by mitochondrial gene flow between sympatric species with
      incomplete reproductive isolation (sibling species). Based on our results
      together with the earlier data on nuclear and mitochondrial gene sequences of
      some other species from the phylogenetic group plumosus, a scheme of phylogenetic
      relationships within this group is proposed. This scheme is in many ways
      different from the traditional view on the evolutionary relationships among
      species of the plumosus group.

PMID- 11963559
TI  - [Predicting efficiency of selection on reproductive traits in the medicinal leech
      Hirudo medicinalis L].
AB  - A set of selection measures for increasing reproduction efficiency in Hirudo
      medicinalis has been developed. The optimal values of reproductive traits
      corresponding to the highest progeny number were determined and recommended. The
      probability of correlated selection response in traits "number of threads in a
      cocoon" and "weight of threads" was estimated. Based on earlier results on
      phenotypic variation and heritability of reproductive traits in medicinal leech,
      efficiency of different selection modes was predicted.

PMID- 11963560
TI  - [Residual variation of morphochronometric traits in hybrid tomatoes: analysis and
      possible mechanism of emergence].
AB  - Different expressivity of several morphometric and chronometric traits in tomato
      plants having similar genetic composition in the identical environmental
      conditions manifested as genotypic residual variation. Using correlation and
      artificial neural network analyses, we determined the relationship between
      productivity and other morphochronometric parameters. It was shown that
      chronology of the development may be important for the determination of
      productivity. Random epigenetic modifications independent of environmental
      factors are considered to underlie the residual variation. The different trait
      expression in different plants may lead to higher phenotypic diversity of a
      population characterized by low gene polymorphism.

PMID- 11963561
TI  - [Study of the backcross progeny of barley-wheat hybrids by the RAPD and RAMPO
      methods].
AB  - The genomes of alloplasmic wheat lines were analyzed by PCR-based methods: random
      amplified polymorphic DNA (RAPD) and random amplified microsatellite polymorphism
      (RAMPO). Lines L-16(1) and L-17(2) were obtained by three backcrosses and line L
      79(10), by four backcrosses of the barely-wheat hybrid Hordeum vulgare (2n = 14)
      (variety Nepolegayuschii) x Triticum aestivum (2n = 42) (variety Saratovskaya 29)
      with different common wheat varieties. These lines proved to be euploid (2n =
      42). The aneuploid line L-9 (2n = 43 + t) was obtained after a second backcross
      of the hybrid H. geniculatum All. (2n = 28) x T. aestivum (2n = 42) (Pyrotrix 28)
      with the variety Pyrotrix 28. The RAPD patterns of L-16(1) and L-17(1) contained
      fragments present only in the patterns of the parental wheat varieties and, in
      addition, fragments absent from the latter. This fragment from the pattern of L
      16(1) was cloned. Analysis of its primary structure showed that the difference
      between L-16(1) and the parental wheat genotypes may be related to a mutation
      that had occurred during the development of the alloplasmic line at the binding
      site of an arbitrary primer. The genomes of plants of the lines L-79(10) and L-9
      contain, in addition to the RAPD fragments of wheat, those characteristic of
      barley. RAMPO revealed higher polymorphism level among wheat varieties than that
      detected by RAPD. The hybridization patterns of the lines L-16(1), L-17(1), and L
      79(10) contained fragments specific for wheat, and the patterns of L-9 contained
      both wheat and barley fragments.

PMID- 11963562
TI  - [Stimulated repopulation as a basis of antimutagenesis and the adaptive response
      in plants].
AB  - Wheat seeds were used to study (1) modification of the radiation adaptive
      response (AR) with antioxidant anphen and (2) modification of the clustogenic
      effect of N-methyl-N-nitrosourea (MNU) with various agents. Pretreatment with
      anphen enhanced AR. Each pretreatment (irradiation with 0.25 Gy, treatment with
      anphen, treatment with anphen followed by irradiation with 0.25 Gy) decreased
      aberration frequency. This parameter proved to be in a linear dependence with
      mitotic index (MI) with correlation coefficient -0.978; the regression line
      passed through the point corresponding to spontaneous MI and spontaneous
      aberration frequency. Upon treatment with MNU, the antimutagenic effect was
      observed for various pretreatments (a low concentration of MNU, antioxidant
      phenoxan, irradiation with 0.25 Gy). Again, MI and aberration frequency were in
      inverse proportion with correlation coefficient -0.99, and the regression line
      passed through the point with spontaneous MI and spontaneous aberration
      frequency. The same dependence was observed for previously published data on
      modification of radiation AR with phenoxan. The results were hard to explain in
      terms of the repair-associated mechanism of AR and the antimutagenic effect.
      Hence, a nonspecific inducible process of stimulated repopulation was assumed to
      be a common mechanism of AR and the antimutagenic effect in plants.

PMID- 11963563
TI  - [Genetic analysis of mutation sy2 which causes nonhomologous meiotic synapsis in
      chromosomes of diploid rye Secale cereale L].
AB  - Partially nonhomologous (heterologous) synapsis of meiotic chromosomes in a
      spontaneous desynaptic mutant form of rye is determined by two recessive genes,
      sy2a and sy2b, that have independent expression and inheritance. The third gene,
      dominant inhibitor suppressing the mutant phenotype, has been revealed in hybrid
      combinations between sy2 mutants and lines segregating other meiotic mutants:
      sy10 (heterologous synapsis), sy1, and sy9 (asynapsis). All three genes
      determining desynapsis (sy2a, sy2b, and I) were shown to be nonallelic to
      monogenic mutations sy10, sy1, and sy9, inherited independently of them and
      expressed at later stages of prophase I than the sy10 gene. The possibility of
      modifying monogenic segregation of mutation sy2 by gametophyte selection for a
      locus linked to the gene expressed as sy2 at particular frequencies of
      recombination between this gene and selected locus is discussed.

PMID- 11963564
TI  - [Phylogenetic relationship of mitochondrial DNA in salmonids of the subfamily
      Salmoninae: analysis of the cytochrome b gene sequences].
AB  - On the basis of comparison of the cytochrome b gene nucleotide sequences from
      genetic databases, the possible phylogenetic relationships of mitochondrial DNA
      (mtDNA) among all major lineages of Salmoninae (Brachymystax, Parahucho,
      Salvelinus, Salmo, Parasalmo, and Oncorhynchus) were examined. Three different
      phylogenetic methods (UPGMA, NJ, and ML) yielded phylogenetic trees of
      essentially the same topology: (((Brachymystax, Parahucho), Salvelinus, Salmo),
      (Parasalmo, Oncorhynchus)). The results obtained using the maximum parsimony
      method were less clear. Apparently, the divergence of the main salmonid lineages
      occurred during a relatively short time period; hence, the number of synapomorphs
      marking the order of their divergence was extremely low. This may account for the
      relative failure to use the maximum parsimony method of phylogenetic
      reconstruction. The problem of concordance of mtDNA and species phylogenetic
      schemes is discussed. Their discrepancy in salmonids may be caused by
      interspecific introgressive hybridization.

PMID- 11963565
TI  - [Age variation of the phenotypic expression and the inheritance of the IgG system
      of immunoglobulin allotypes in the pig].
AB  - The specificity of phenotypic expression and inheritance of immunoglobulin
      allotypes IgG1a and IgG2b in pigs are discussed. It was shown that a negative
      state by both these allotypes is repeatedly found among newborn pigs but is
      extremely rare in pigs older than one month. A model, which simultaneously
      describes the genetic determination of allogroups formed by allotypes IgG1a and
      IgG2b and the dynamics of ontogenetic expression of individual genotype by system
      IgG with a result of a visually registered phenotype, was developed. Allele
      frequencies by system IgG were assessed in populations of domestic pigs of
      productive breeds, laboratory miniature pigs, and wild Eurasian pigs.

PMID- 11963566
TI  - [Results of a cytogenetic study of populations with different radiation risks in
      the Semipalatinsk region].
AB  - A cytogenetic study was conducted for the first time on human populations
      neighboring the Semipalatinsk nuclear test site (STS) and exposed to ionizing
      radiation for a long period of time. In populations with the extreme and maximum
      radiation risks, high frequencies of radiation-induced chromosomal markers,
      including acentric fragments (1.99 +/- 0.10 per 100 cells), dicentrics (0.23 +/-
      0.01), ring chromosomes (0.38 +/- 0.14), and stable chromosomal aberrations (1.17
      +/- 0.02), were found. These frequencies significantly exceeded those in control
      populations. The spectrum of chromosomal aberrations and the frequencies of the
      aberrations of different types in persons living in the areas with the highest
      radionuclide contamination confirmed the mutagenic effect of radiation on
      chromosomes in the human populations studied.

PMID- 11963567
TI  - [Analysis of gene complexes predisposing to coronary atherosclerosis].
AB  - The following seven polymorphic marker loci of genes responsible for
      predisposition to coronary atherosclerosis (CAS) were studied: the ACE locus
      responsible for angiotensin-converting enzyme insertion/deletion polymorphism for
      the presence or absence of the Alu insertion in the gene; the F13, PLAT, and
      APOA1 loci, controlling the clotting factor 13, plasminogen-activating tissue
      factor, and apolipoprotein A, respectively; the MTHFR and AGT polymorphic loci
      responsible for point mutations in methylenetetrahydrofolate reductase and those
      in angiotensinogen, respectively, and the NOS3 locus controlling the number of
      tandem repeats in the nitric oxide synthase gene. These loci are located on
      different chromosomes and encode products involved into various metabolic
      pathways leading to CAS. In the populations studied, significant differences
      between healthy subjects and patients predisposed to cardiovascular diseases were
      revealed with regard to the above seven markers. The 174M allele (T174M
      polymorphism in the ACE gene) was significantly associated with coronary
      atherosclerosis. It was found that specific gene combinations are involved in the
      CAS development and determine variation in the pathogenetically important
      quantitative traits.

PMID- 11963568
TI  - [Polymorphism of the Y-chromosome diallelic loci in the ethnic populations of the
      Altai-Sayan region].
AB  - Using the data on five biallellic Y-chromosome loci (DYS199, 92R7, SRY1532, RBF5
      and DYS287) polymorphism, genetic structures of the five Turkic-speaking ethnic
      groups of the Altai-Sayan highland (Tuvinians, Sojots, Shorians, Khakassians, and
      Southern Altaians (Altai-Kizhi), were described. The gene pools of the
      populations examined were characterized by the presence of pronounced paleo
      Caucasoid component (92R7-T-lineages). The frequency of this component increased
      westward, reaching more than 70% in Shorians and Southern Altaians. Haplotype TAT
      C (RBF5 locus) was observed in all populations, except Shorians, with the
      frequencies varying from 5.4% in Altai-Kizhi to 18.8% in Khakassians. The Alu
      insertion in the DYS287 locus was revealed only in the Altaian sample with the
      frequency of 3.3%. It was established that the Altai-Sayan populations studied
      split into two statistically significantly different groups. One of the groups
      was represented by Tuvinians, Sojots, and Khakassians, while another one was
      comprised of Shorians and Altaians.

PMID- 11963569
TI  - [Hereditary diseases of nervous system in the population of Vladimir province].
AB  - The first population genetic study of hereditary disorders of the nervous system
      (HDNS) in Vladimir oblast was carried out. A total of 1,622,900 subjects,
      including 1,306,200 from the urban and 316,700 from the rural population, were
      tested. The population examined was characterized by virtually homogenous ethnic
      structure, with Russians constituting 95.76%. Pooled prevalence of HDNS in
      Vladimir oblast corresponded to the average prevalence for other Russian
      populations. Substantial differences between urban and rural populations in
      respect of the population load of HDNS and its nosological structure were not
      observed. A total of 22 nosological forms of HDNS were revealed, including
      thirteen autosomal dominant (193 families with 272 affected individuals), seven
      autosomal recessive (59 families with 66 affected individuals), and two X-linked
      (15 families with 17 affected individuals) diseases. The composition of the HDNS
      spectrum "nucleus" in Vladimir oblast displayed a number of differences from that
      in the majority of other populations examined. The HDNS in different regions of
      the area tested were characterized by different prevalence and spectrum. The data
      obtained may constitute a basis for regional registration of HDNS in Vladimir
      oblast.

PMID- 11963570
TI  - [The use of the expectation-maximization (EM) algorithm for maximum likelihood
      estimation of gametic frequencies of multilocus polymorphic codominant systems
      based on sampled population data].
AB  - Estimation of gametic frequencies in multilocus polymorphic systems based on the
      numerical distribution of multilocus genotypes in a population sample ("analysis
      without pedigrees") is difficult because some gametes are not recognized in the
      data obtained. Even in the case of codominant systems, where all alleles can be
      recognized by genotypes, so that direct estimation of the frequencies of genes
      (alleles) is possible ("complete data"), estimation of the frequencies of
      multilocus gametes based on the data on multilocus genotypes is sometimes
      impossible, whether population data or even family data are used for studying
      genotypic segregation or analysis of linkage ("incomplete data"). Such
      "incomplete data" are analyzed based on the corresponding genetic models using
      the expectation-maximization (EM) algorithm. In this study, the EM algorithm
      based on the random-marriage model for a nonsubdivided population was used to
      estimate gametic frequencies. The EM algorithm used in the study does not set any
      limitations on the number of loci and the number of alleles of each locus. Locus
      and alleles are identified by numeration making possible to arrange loops. In
      each combination of alleles for a given combination of m out of L loci (L is the
      total number of loci studied), all alleles are assigned value 1, and the
      remaining alleles are assigned value 0. The sum of zeros and unities for each
      gamete is its gametic value (h), and the sum of the gametic values of the gametes
      that form a given genotype is the genotypic value (g) of this genotype. Then,
      gametes with the same h are united into a single class, which reduces the number
      of the estimated parameters. In a general case of m loci, this procedure yields m
      + 1 classes of gametes and 2m + 1 classes of genotypes with genotypic values g =
      0, 1, 2, ..., 2m. The unknown frequencies of the m + 1 classes of gametes can be
      represented as functions of the gametic frequencies whose maximum likelihood
      estimations (MLEs) have been obtained in all previous EM procedures and the only
      unknown frequency (Pm(m)) that is to be estimated in the given EM procedure. At
      the expectation step, the expected frequencies (Fm(g) of the genotypes with
      genotypic values g are expressed in terms of the products of the frequencies of m
      + 1 classes of gametes. The data on genotypes are the numbers (ng) of individuals
      with genotypic values g = 0, 1, 2, 3, ..., 2m. The maximization step is the
      maximization of the logarithm of the likelihood function (LLF) for ng values.
      Thus, the EM algorithm is reduced, in each case, to solution of only one equation
      with one unknown parameter with the use of the ng values, i.e., the numbers of
      individuals after the corresponding regrouping of the data on the individuals'
      genotypes. Treatment of the data obtained by Kurbatova on the MNSs and Rhesus
      systems with alleles C, Cw, c, D, d, E, e with the use of Weir's EM algorithm and
      the EM algorithm suggested in this study yielded similar results. However, the
      MLEs of the parameters obtained with the use of either algorithm often converged
      to a wrong solution: the sum of the frequencies of all gametes (4 and 12 gametes
      for MNSs and Rhesus, respectively) was not equal to 1.0 even if the global
      maximum of LLF was reached for each of them (as it was for MNSs with the use of
      Weir's EM algorithm), with each parameter falling within admissible limits (e.g.,
      [0, min(PN,Ps)] for PNs). The chi 2 function is suggested to be used as a
      goodness-of-fit function for the distribution of genotypes in a sample in order
      to select acceptable solutions. However, the minimum of this function only
      guarantee the acceptability of solutions if all limitations on the parameters are
      met: the sum of estimations of gametic frequencies is 1.0, each frequency falls
      within the admissible limits, and the "gametic algebra" is complied with (none of
      the frequencies is negative).

PMID- 11963571
TI  - [Investigation of monoamine oxidase gene restriction polymorphism in male
      populations of the Volga-Ural region].
AB  - Restriction polymorphism at the monoamine oxidase A (MAO A) gene was typed in
      eight male populations of the Volga-Ural region (Bashkirs, Chuvashes, Tatars,
      Udmurts, Maris, Mordovians, Komis, and Russians inhabiting the Republic of
      Bashkortostan). Analysis of the MAO A alleles frequency distribution patterns did
      not reveal statistically significant differences between the Volga-Ural
      populations examined. The results obtained suggest genetic homogeneity of the
      populations described in respect of the polymorphic locus examined.

PMID- 11963572
TI  - [Comparison of the protective effect of garlic extract and cell defense during
      adaptive response].
AB  - The resistance of human cell DNA to damaging doses of CdCl2 or gamma radiation
      has been investigated after pretreatment with garlic extract (GE) or with
      adaptive doses of the same mutagens. The adaptive response (AR) and pretreatment
      with GE stabilize the DNA structure in a similar way. In experiments with 4
      nitroquinoline-1-oxide (4-NQO), GE does not stabilize DNA structure but increases
      the rate and volume of repair of induced breaks. 3-Aminobenzamide (3-AB)
      increases the number of DNA breaks induced in experiments with CdCl2, gamma
      radiation, and 4-NQO. This suggests that poly(ADP-ribose)polymerase participates
      defense of cells from mutagens. Thus, it has been demonstrated that cell defense
      from CdCl2 or gamma radiation in experiments with GE and AO is mediated by
      stabilization of DNA structure and in experiments with 4-NQO, by activation of
      repair of DNA breaks induced.

PMID- 11963574
TI  - [Nobel prize 2001 in physiology and medicine is awarded for success in the study
      of cell cycle].

PMID- 11963573
TI  - [Genetic polymorphism of erythrocytic enzymes in Yakut populations].
AB  - Polymorphism of the erythrocytic enzymes PGM1, ACP1, ESD, and GLO1 was found in
      Yakut populations. The allelic frequencies of the polymorphic systems studied
      varied within the following ranges: PGM1*1+, 0.5833-0.7791; PGM1*1-, 0.0345
      0.1176; PGM1*2+, 0.1250-0.2813; ACP1*A, 0.1429-0.3382; ACP1*B, 0.6548-0.8571;
      ESD*2, 0.1250-0.4643; and GLO1*1, 0.0116-0.2845.

PMID- 11963575
TI  - Changing prospects of chemical pathologist in Pakistan.

PMID- 11963577
TI  - Comparison of meropenem with ceftazidime as monotherapy of cancer patients with
      chemotherapy induced febrile neutropenia.
AB  - BACKGROUND: Ceftazidime is commonly used as monotherapy of cancer patients with
      fever and neutropenia. Concern, however, has been raised regarding potential for
      drug resistance due to its widespread use. Meropenem is a new carbapenem with
      more extended antibacterial spectrum including anaerobes. It provides better
      coverage against gram positives. Hence, it may offer an advantage over
      ceftazidime. PATIENTS AND METHODS: We prospectively treated 49 patients
      hospitalized for fever (> 38 degrees C) and neutropenia (ANC < or = 500/cmm) with
      meropenem. We compared their outcome with 50 patients who consecutively received
      ceftazidime in the immediate past for the same indication. RESULTS: Comparison of
      demographic features between the 2 groups revealed no differences in age, gender,
      type of neoplasm, number of patients with prior antibiotic use, number of days
      since chemotherapy, absolute neutrophil count and number of patients previously
      or already hospitalized. Duration of fever, duration of neutropenia and number of
      patients with pyrexia of undetermined origin were also similar. Therapeutic
      outcome was same between the two groups. Eighty four percent of patients
      receiving meropenem and 79% receiving ceftazidime required no modification of the
      initially assigned therapeutic regimen. Two patients receiving meropenem died.
      Toxicity was minimal. CONCLUSION: We conclude that meropenem offers no
      significant advantage over ceftazidime in the management of neutropenic febrile
      patients.

PMID- 11963576
TI  - Clinical and laboratory features of systemic lupus erythematosus (SLE) in
      Pakistani patients.
AB  - OBJECTIVES: To study the clinico-pathological features of systemic lupus
      erythematosus (SLE) in Pakistani patients at the time of presentation in the four
      teaching hospitals of Rawalpindi-Islamabad area. SETTINGS: Department of
      Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Military
      Hospital (MH), Rawalpindi, Armed Forces Institute of Urology (AFIU), Rawalpindi,
      Combined Military Hospital (CMH), Rawalpindi, Department of Rheumatology,
      Pakistan Institute of Medical Sciences (PIMS), Islamabad. SUBJECTS: Patients
      suffering from SLE, diagnosed on the basis of the ARA criteria. MAIN OUTCOME
      MEASURES: Clinico-pathological features at the time of presentation. RESULTS:
      Twelve male patients in age range 5-30 years (mean 21.6 years) and 38 female
      patients in age range 8-37 years (mean 22.2 years) were included in the study,
      showing a female to male ratio of 3:1. Fever was the most common presenting
      feature (100%), followed by arthralgias/arthritis (98%), malar rash (64%) and
      oral ulcers (58%). Laboratory results showed antinuclear antibody to be positive
      in all patients followed by anti double stranded DNA antibodies (anti DNA
      antibodies: 64%), anti extractable nuclear antigen antibodies (anti ENA
      antibodies: 64%) and evidence of complement consumption in 64% of the patients.
      Erythrocyte Sedimentation Rate (ESR) was found to be increased with a mean of 64
      mm first hour fall in males and a mean of 87 mm first hour fall in the female
      patients. The C reactive protein was detected to be normal or marginally
      increased inspite of the increased ESR with mean of 7 mg/l for male patients and
      5 mg/1 for the females. CONCLUSION: The subject patient population presented
      almost universally with fever and arthralgias or arthritis in combination with
      malar rash or oral ulcers and in some patients a combination of all of the above
      was observed. A combination of positive anti nuclear antibody test, evidence for
      consumption of the complement in form of low C4 and C3, increased ESR and low C
      reactive protein were found to be a sensitive and cost effective set of
      laboratory findings for the diagnosis of patients suffering from SLE. The above
      mentioned set of clinical and laboratory features would help in the correct and
      early diagnosis of patients suffering from SLE, a relatively rare disease, in the
      busy medical out patient departments in our set up.

PMID- 11963578
TI  - Diagnosis and management of lost intrauterine contraceptive device.
AB  - OBJECTIVE: To study the pattern of referral, method of diagnosis and management
      of patients admitted with lost Intrauterine Device (IUD). METHODS: A prospective
      study was conducted about lost intrauterine contraceptive devices and its
      management, in Gynaecology Department of Nishtar Hospital, Multan. Twenty eight
      patients with lost IUD were identified out of 7816 gynaecology admissions, during
      this period. The diagnosis was made on ultrasonography. RESULTS: IUDs were
      removed after dilatation of cervix and exploration of uterine cavity in 20
      patients. Five cases underwent laparotomy, in 2 cases laparoscopic removal was
      done and in one case IUD was taken out through proctoscope. In most of the cases
      IUD was inserted by untrained personnel. CONCLUSION: It is recommended that IUDs
      should be inserted after proper case selection by trained medical professionals.

PMID- 11963579
TI  - Strengthening primary health care and family planning services in Pakistan: some
      critical issues.
AB  - OBJECTIVE: The Lady Health Workers (LHWs) under the Ministry of Health and the
      Village-based Family Planning Workers (VBFPWs) under the Ministry of Population
      Welfare are mandated to bring services to the people and are often the only
      health care resource available particularly for women. This study was conducted
      to understand the problems faced by the LHWs and VBFPWs in their routine work.
      STUDY DESIGN: A situational analysis followed by focus group discussions
      conducted with a cross-section of LHWs and VBFPWs in four districts, one from
      each province. RESULTS: Findings reveal that LHWs and VBFPWs are faced with a
      number of problems that severely limit their effectiveness. Findings suggest that
      the population/health worker ratios vary considerably from one district to
      another. Moreover, these two categories of workers differ considerably in terms
      of level of education, training and skills. There is lack of well-designed client
      record cards, proper training and backup support, including emergency obstetric
      care, to cover the range of essential services demanded by the consumers and a
      lack of information feedback. CONCLUSION: These issues need to be recognized and
      addressed to further strengthen primary health care and family planning services
      in the country. The paper presents some of the important findings of the survey
      and focus group discussions conducted by the Community Health Sciences Department
      of the Aga Khan University as part of a broader study funded by the United
      Nations Population Fund. These findings have serious implications for future
      primary health care and family planning policies in Pakistan.

PMID- 11963580
TI  - Community knowledge, attitude and practices regarding sexually transmitted
      infections in a rural district of Pakistan.
AB  - OBJECTIVE: To determine knowledge, attitude and practices regarding sexually
      transmitted infections in district Khairpur, Sindh, Pakistan. DESIGN AND
      METHODOLOGY: A needs assessment study employing a community based survey, key
      informant interviews and focus group discussions was conducted in all seven sub
      districts of the district. This paper is based on the results of the key
      informant interviews and the focus group discussions. Thirty interviews and six
      group discussions were held with members of the community and with the health
      care providers. RESULTS: There was little awareness regarding causes and
      prevention of sexually transmitted infections in the community. The situation was
      slightly better among health care providers. While health care providers believed
      that the prevalence of sexually transmitted infections is high, the community did
      not consider themselves at risk. The community believed that these diseases are a
      problem among a sub-population of male adolescents, especially those who have
      homosexual relations. However, due to social norms, they rarely discussed such
      health problems with other family members or elders. Adolescents with any sexual
      health problems visit hakims and quacks. The community was aware about aetiology
      and some of the risk factors associated with AIDS and hepatitis, most probably
      due to the recent public health campaigns against both diseases. CONCLUSION:
      Considering the suspected high prevalence of sexually transmitted infections and
      the relative lack of knowledge, it is imperative that a public health
      intervention be initiated. This must include educating not only the community but
      also the health workers. The governments' initiative to train community workers
      in reproductive health is a step in the right direction.

PMID- 11963581
TI  - Analysis of inconclusive breast FNA by triple test.
AB  - OBJECTIVE: To evaluate the efficiency of triple test for non-diagnostic
      (inconclusive and inadequate) FNAs of palpable breast lesions and to compare our
      results with the literature. METHODS: A retrospective analysis was done on cases
      that were having cyto-histological correlation with clinical and radiological
      follow up. Out of 446 FNAs performed at our institute during the period of 15
      years, only 16 cases were discovered fulfilling the above criteria and these were
      reviewed blindly and scored. The triple test was applied to each case. Each
      component of the triple test was assigned 1, 2, or 3 points for a benign,
      suspicious, or malignant result, respectively, yielding a total triple test score
      (TTS) of these 16 cases. RESULTS: Three out of 16 specimens were unsatisfactory
      and rest 13 cases inconclusive (i.e., suspicious) cytologically, diagnosed as
      having scant atypical cells. All malignant cases scored above 6 except one case
      that scored 5. The two benign cases scored 1 and 3. On histological follow up 2
      of the unsatisfactory cases turned out as fibroadenoma (scored 1 and 3) and one
      as malignant (scored 5). Among inconclusive cases all turned out to be malignant
      on histological follow up (all scored 6 and above). High clinical suspicion was
      present in all 14 cases that were proved malignant in histological follow up.
      Radiological diagnosis of malignancy was present in 11 of 14 malignant cases,
      suspicious in two malignant cases and in 1 of 2 fibroadenoma cases. All cases
      underwent surgical removal of the mass as a result of clinical or radiological
      suspicion. CONCLUSION: Triple test can reliably guide the evaluation and
      treatment of palpable breast masses. Masses that score 6 points or higher are
      malignant and should undergo definitive therapy; masses that score 4 points or
      lower are benign and may be clinically followed up. Only those masses that score
      5 points require open biopsy. Our results were in concordance with other larger
      studies published in the literature. We recommend utilizing the three diagnostic
      parameters of cytology, clinical findings and radiology, the triple test, to
      achieve the best diagnostic accuracy in breast FNAs and patient management.

PMID- 11963582
TI  - Lipid profile in children with insulin dependent diabetes mellitus.
AB  - OBJECTIVE: To evaluate serum lipids in children with type 1 diabetes mellitus and
      its relation to glycemic control, in comparison with matched controls. SETTING:
      Basrah Maternity and Children Hospital, Basrah, Iraq. METHOD: Lipid profile was
      studied in 32 children (17 males and 15 females) with type 1 diabetes mellitus
      from October 1999 to September 2000. Seventy seven non-diabetic children (35
      males and 42 females) admitted with acute illness in the same hospital were
      selected as controls. RESULTS: The age and BMI was similar in both groups. The
      mean total cholesterol, triglycerides, HDL-C, LDL-C, VLDL-C and LDL-C/HDL-C ratio
      were significantly higher in diabetic children compared to control group. There
      was no significant difference in the levels of Apo O and Apo B in both groups.
      CONCLUSION: Children with type 1 diabetes should be screened for serum lipids as
      significant lipid abnormalities are related to glycemic control. Both can be
      improved with dietary management and insulin therapy.

PMID- 11963583
TI  - Reproductive health in Pakistan: evidence and future directions.

PMID- 11963584
TI  - Come to mental health in C.O.M.E.

PMID- 11963585
TI  - View box case--1. Pyogenic liver abscess.

PMID- 11963586
TI  - Acute myocardial infarction: profile and management at a tertiary care hospital
      in Karachi.
AB  - OBJECTIVE: Acute Myocardial Infarction (AMI) is a rising epidemic in developing
      countries. While studies in the West have established the characteristics and
      management of AMI patients, comprehensive data reflecting these issues in the
      Pakistani subjects is scarce. This study examined the profile and management of
      AMI in patients hospitalized at a tertiary care hospital in Karachi, Pakistan.
      METHODS: Three hundred forty four patients admitted in 1998 with the diagnosis of
      AMI met our inclusion criteria. Data on presentation, investigations, monitoring
      and therapy was obtained. Chi-square and t tests were used to analyze the data.
      RESULTS: Out of 344 patients with AMI, 71% were males; 58% had a Q wave MI.
      Majority of the patients who presented within 2 hours of symptom onset (36%), had
      chest pain. Patients with dyspnea and no chest pain were more likely to present
      after 12 hours of the onset of symptoms. In-house mortality was found to be
      10.8%. Low HDL and diabetes was associated with in-hospital complications. Twenty
      nine percent of patients were given thrombolytic therapy with a mean door-to
      needle time of 1 hour 36 minutes; 33% of patients who were eligible of
      Streptokinase did not receive it. Cardiac catheterization was performed in 28%
      patients. Echocardiography and Exercise Tolerance Test, both under utilized, were
      performed in 67% and 16% of patients, respectively. Two hundred sixteen (70%)
      patients discharged from hospital were contacted via telephone and the 1-year
      mortality rate among them was 28%. CONCLUSION: The profile and management of AMI
      was in coherence with earlier, Western studies. Chest pain units need to be
      established in the Emergency Room. Patients should be risk stratified prior to
      discharge. Public awareness regarding primary and secondary prevention and
      symptoms of AMI needs to be increased.

PMID- 11963588
TI  - False memory syndrome and therapist liability to third parties for emotional
      distress injuries arising from recovered memory therapy: a general prohibition on
      liability and a limited liability exception.

PMID- 11963587
TI  - Determination of antimicrobial activity of Cefaclor on common respiratory tract
      pathogens in Pakistan.
AB  - OBJECTIVE: To determine the antimicrobial activity of Cefaclor against common
      respiratory tract pathogens isolated from patients in Pakistan. SETTING:
      Department of Microbiology, Liaquat National Postgraduate Medical Centre,
      Karachi. METHOD: A laboratory analysis was done on 466 isolates of respiratory
      tract pathogens collected from 13 laboratories from all over Pakistan. Antibiotic
      sensitivity test was done by Kirby Bauer disc diffusion method and MIC of
      Cefaclor was determined by 'E' test. RESULT: Of the 163 Streptococcus pneumoniae,
      87 Moraxella catarrhalis and 216 Haemophilus influenzae > 95% isolates were
      susceptible to Cefaclor. The MIC 90 of all these pathogens were < 2 ug.
      CONCLUSION: Resistance of respiratory tract pathogens to the 2nd generation
      Cephalosporin, Cefaclor is very low. MIC 90 of Cefaclor against all three common
      respiratory tract pathogens is < 2 ug, which indicates that Cefaclor would be
      effective in more than 90% of cases infected with these bacteria.

PMID- 11963589
TI  - Electronic resumes are crucial advancement tools.

PMID- 11963590
TI  - Internal promotions can enhance PFS strategic success.

PMID- 11963591
TI  - Data trends. Glass tube replacement costs on the rise.

PMID- 11963592
TI  - Solving the revenue-cycle problem.

PMID- 11963593
TI  - The Enron effect.

PMID- 11963594
TI  - Bush plan for nation's health meets budget reality.

PMID- 11963595
TI  - Nelson: clinical improvements hold key to reducing cost pressures.

PMID- 11963596
TI  - Practical considerations for conducting effective billing audits.
AB  - Healthcare organizations need to ensure that they are in compliance with
      government regulations, especially with the increased vigilance by the HHS Office
      of Inspector General (OIG) in investigating fraud and abuse. After an OIG audit
      of claims submitted to Medicare by its teaching and resident physicians, the
      Clinical Practices of the University of Pennsylvania (CPUP), Philadelphia,
      Pennsylvania, entered into a settlement that included significant financial
      penalties and a five-year corporate integrity agreement. Lessons learned from the
      experience may be helpful to other providers in ensuring that their billing
      practices are in regulatory compliance. As a precautionary measure, providers can
      undertake their own audits, whether routine or focused. Audits can help providers
      uncover areas of potential abuse and take steps to correct the problems.

PMID- 11963597
TI  - Integrated, automated revenue management for managed care contracts.
AB  - Faced with increasing managed care penetration and declining net revenue in
      recent years, healthcare providers increasingly are emphasizing revenue
      management. To streamline processes and reduce costs in this area, many
      healthcare providers have implemented or are considering automated contract
      management systems. When selecting such a system, healthcare financial managers
      should make certain that the system can interface with both patient-accounting
      and decision-support systems of the organization. This integration enhances a
      healthcare provider's financial viability by providing integrated revenue
      management capabilities to analyze projected performance of proposed managed care
      contracts and actual performance of existing contracts.

PMID- 11963598
TI  - The Medicaid managed care grievance process: new protections for beneficiaries.
AB  - The Centers for Medicare and Medicaid Services (CMS) recently proposed
      regulations to enhance protection of the rights of Medicaid managed care
      enrollees to appeal decisions made by their managed care plans. The regulations
      would require both internal and external beneficiary grievance processes that
      could have a significant effect on managed care organizations with multiple lines
      of business operating in several states. Managed care organizations may find it
      worthwhile to develop a standard grievance process that meets Medicaid and
      Medicare requirements and can be used by enrollees in commercial plans. In
      addition to saving money and reducing confusion, a well-structured internal
      grievance process for all product lines would be useful as part of a quality
      improvement initiative. Data from grievances may provide information that can
      help healthcare providers update medical protocols.

PMID- 11963599
TI  - Developing organizational charity-care policies and procedures.
AB  - A lack of standards in healthcare organizations often makes it difficult to
      consistently define and report charity care. Accurately documenting services
      provided to patients who are unwilling or unable to pay can be difficult for many
      organizations. Temple East, Inc., Philadelphia, Pennsylvania, established several
      policies in an attempt to clarify its charity-care provisions. Among the
      organization's guiding principles were that all unreimbursed costs of caring for
      patients who are either uninsured or enrolled in a Medicaid program and all bad
      debt directly attributable to services to low-income or uninsured patients should
      be included as charity care. The organization also determined that contractual
      allowances and disallowances for payers other than government payers should not
      be included as charity care. Determining clear, unambiguous definitions for
      several terms related to charity care also helped the organization better track
      and document its charity-care services--a task that will become increasingly
      important for hospitals in the future.

PMID- 11963600
TI  - IRS Notice 2002-8 clarifies split-dollar life insurance arrangements.
AB  - Healthcare organizations that sponsor split-dollar life insurance arrangements
      for employees need to understand the tax treatment of such arrangements. IRS
      Notice 2002-8 clarifies this issue. The notice announces the IRS's intention to
      publish final regulations regarding the taxation of split-dollar life insurance,
      outlines the expected provisions to be included in the regulations, provides
      guidance on the value of economic benefit provided under such arrangements, and
      issues rules for the taxation of arrangements entered into before the publication
      of final rules.

PMID- 11963602
TI  - Optimize APC revenue with process-oriented assessments.
AB  - To maintain or improve revenue streams under the Medicare outpatient prospective
      payment system (PPS), healthcare financial managers should use a process-oriented
      approach to assess the effectiveness of revenue capture in departments most
      affected by the PPS's use of ambulatory patient classifications, which typically
      include the radiology, cardiology, and emergency departments. Such an assessment
      should be conducted by a multidisciplinary team with senior management support.
      The team ideally should include the CFO, COO, and leaders from the departments to
      be assessed. Such an assessment process should consist of five basic phases:
      chargemaster/charge-capture analysis, revenue-capture process assessment, claims
      review, development of implementation strategies, and monitoring.

PMID- 11963603
TI  - CMS establishes new audit requirements, proposes new overpayment rule.
AB  - Two recent publications of the Centers for Medicare and Medicaid Services (CMS)
      seem to belie the view that providers can expect to see an easing of their
      regulatory burden under the Bush Administration. Program memorandum (PM) A-01
      141, issued in December 2001, sets forth the agency's expectations with respect
      to audits of Medicare cost reports. PM A-01-141 instructs Medicare intermediaries
      "as a general rule" not to reopen a cost report or settle an appeal if the
      request for reopening or appeal is based on submission documentation that was not
      made available at the time of the audit. A proposed rule issued by CMS on January
      25, 2002, would require a Medicare provider to identify and return an overpayment
      to its Medicare intermediary within 60 days after the provider identifies the
      overpayment. The proposed rule defines "overpayment" but leaves many issues open
      to interpretation.

PMID- 11963604
TI  - Achieving results through accountability management.

PMID- 11963605
TI  - HIPAA electronic transaction standards: E-commerce or compliance?

PMID- 11963606
TI  - Feds issue new ruling on ambulance restocking.

PMID- 11963607
TI  - Responder safety.

PMID- 11963608
TI  - Biological & chemical terrorism: a review for the EMS provider.

PMID- 11963609
TI  - Enhanced Consequence Management, Planning and Support System (ENCOMPASS).
      Enabling an effective, coordinated response.
AB  - In an incident involving a chemical or biological terrorist attack, a staggering
      number of situations must be managed--casualties must be triaged and treated;
      nearby residents must be isolated from the impending hazard; a culprit may be on
      the loose. No single entity can provide adequate response; experts are needed
      from many organizations , including fire and police departments, hazardous
      materials units and medical facilities. How can organizations communicate and
      coordinate to yield an effective response? This article introduces the Enhanced
      Consequence Management, Planning and Support System (ENCOMPASS), a software
      system designed to address this issue.

PMID- 11963610
TI  - Tour of terror: an NBC primer.

PMID- 11963611
TI  - Poison control: patient assessment and management.

PMID- 11963612
TI  - EMS toxicology: approach to the poisoned patient.

PMID- 11963613
TI  - Developing leadership skills in the volunteer EMS system.

PMID- 11963614
TI  - Breathless.
AB  - This case presented the scenario of a patient who had severe bronchospasm from an
      unknown etiology. Further, she had difficulty speaking and denied any past
      medical history, which made a diagnosis more difficult. Prehospital providers
      were challenged with determining the differential diagnosis for bronchospasm and
      hypoxemia. Was the patient experiencing an anaphylactic reaction, acute asthmatic
      attack or something else? The key here, once again, is conducting a thorough
      assessment and patient history. Remember, all that wheezes is not asthma;
      therefore, providers in this case had to determine if the patient was suffering
      something such as anaphylaxis, asthma, bronchitis, pneumonia or even congestive
      heart failure (CHF). Typically, anaphylaxis and asthma affect ventilation, not
      oxygenation, so until the late stages of anaphylaxis or asthma, the patient will
      have difficulty moving air, but will be oxygenating OK. We understand that many
      respiratory conditions can cause wheezing, but CHF? Yes: As left ventricular
      function diminishes and leads to increased pulmonary pressure, serum begins to
      leak out of the pulmonary vessels and into the interstitial space. As the
      interstitial pressure increases, it causes narrowing of the bronchioles, and air
      traveling through the narrowed bronchioles causes the wheezing sound. Fluid may
      also be leaking out of the pulmonary capillaries and occupying space in the
      alveolar sacs. When the interstitial pressure is high and the bronchioles
      continue to narrow, providers may initially hear only the wheezing and not the
      crackles from the smaller airways. In these conditions, oxygen is not exchanged
      adequately into the blood, and the patient becomes hypoxemic. Good assessment and
      patient history will guide the EMS provider to the cause of bronchospasm. For
      example, does the patient have a history of asthma? If yes, asthma is likely to
      be the cause. Does the patient have any rash, hives or swelling? If yes,
      anaphylaxis is likely the cause. Is the patient elderly, and does he/she show
      pedal edema, JVD, hypoxemia and/or distended neck veins? If yes, CHF may be the
      cause. [table: see text] There are questions regarding the use of bronchodilators
      in patients suffering CHF. If a CHF patient is wheezing (bronchospasm), then a
      beta-2 selective breathing treatment may be appropriate, along with nitrates and
      diuretics. Oxygenation is the critical problem in CHF, and hypoxemia will
      continue to worsen cardiac function. Remember, both bronchoconstriction and
      alveolar sacs filling with fluid will impair oxygenation of the RBCs and
      ultimately the vital organs. Focused prehospital management of CHF is aggressive
      in restoring oxygenation. For example, many agencies are now using oxygen,
      nitrates, ACE inhibitors and CPAP. By better understanding the pathophysiology of
      respiratory emergencies and their differential diagnosis, we will improve patient
      outcomes.

PMID- 11963615
TI  - Ten steps for EMS survival at clandestine methamphetamine labs.

PMID- 11963616
TI  - Overcoming the inertia: EMS in Siberia, Part 1.

PMID- 11963617
TI  - An anatomical study of the recurrent laryngeal nerve: its branching patterns and
      relationship to the inferior thyroid artery.
AB  - The aim of this study was to provide information about the morphology and
      topography of the recurrent laryngeal nerve (RLN), its external features and
      branches, as well as its relationship to the inferior thyroid artery, the
      inferior horn of the thyroid cartilage and the thyroid gland. The RLNs in 50
      adult cadavers (100 sides) were dissected and analyzed. A communicating loop
      connecting one branch of the RLN to another or a twig originating from the
      cervical sympathetic trunk was present in 13 of 100 sides. A double left RLN
      appeared in 2 sides; a right non-recurrent inferior laryngeal nerve appeared in
      one side. All of the RLNs, including looped ones, bifurcated into laryngeal
      branches and extralaryngeal branches, with most of the former further dividing
      into the anterior and posterior branches entering the larynx. The relations of
      the RLN to the inferior thyroid artery, the inferior horn of the thyroid
      cartilage and the thyroid gland were inconstant. The information gained from this
      study will be of value in thyroid surgery.

PMID- 11963618
TI  - Descriptive anatomy of the femoral portion of the iliopsoas muscle. Anatomical
      basis of anterior snapping of the hip.
AB  - Anterior hip snapping is a rare clinical observation. The physiopathological
      hypothesis currently held is a sudden slip of the iliopsoas tendon over the
      iliopectineal eminence. For symptomatic cases, a surgical technique is proposed.
      The aim of this work is to describe the anatomy of the femoral portion of the
      iliopsoas, which is the target of surgery. We have studied, through dissection of
      embalmed cadavers, the different components of the musculotendinous complex
      forming the femoral portion of the muscle and the gliding apparatus associated
      with it. The psoas major tendon exhibited a characteristic rotation. The iliacus
      tendon, more lateral, received the most medial iliacus muscular fibers, then
      fused with the main tendon. The most lateral fibers, starting in particular from
      the ventral portion of the iliac crest, ended up without any tendon on the
      anterior surface of the lesser trochanter and in the infratrochanteric region.
      The most inferior muscular fibers of the iliacus, starting from the arcuate line,
      joined the principal tendon of the psoas major passing around it by its
      ventromedial surface. An ilio-infratrochanteric muscular bundle was observed, in
      a deeper position, under the iliopsoas tendon; it arose from the interspinous
      incisure and on the anterior inferior iliac spine, ran along the anterolateral
      edge of the iliacus and inserted without any tendon onto the anterior surface of
      the lesser trochanter of the femur and in the infratrochanteric area. The
      iliopectineal bursa was studied on horizontal cross sections of a frozen pelvis
      and on 5 of the non-frozen preparations after dividing the iliopsoas tendon. The
      iliopectineal bursa had the shape of a 5 to 6-cm high and 3-cm wide cavity; in
      its upper part, it was divided into 2 compartments: a medial compartment for the
      main tendon and a lateral compartment for the accessory tendon.

PMID- 11963619
TI  - Morphometrical study of the arterial perforators of the deep inferior epigastric
      perforator flap.
AB  - Although abdominal perforator flaps based on a cutaneous branch of the deep
      inferior epigastric artery (DIEP flaps) have many advantages, preparing these
      flaps is technically difficult and requires great skill, especially as the
      portion of the artery running under the anterior rectus abdominis sheath must be
      operated upon "blind". To allow easier preparation and elevation of a DIEP flap
      pedicle, we propose that the arterial perforator should: 1) be more than 1.0 mm
      large; 2) run a straight intramuscular course, parallel to the rectus abdominis
      m. fibers, with no large muscular branches; and 3) have only a short portion
      running immediately under the anterior rectus abdominis sheath. We examined 329
      perforators (more than 0.5 mm in diameter at the anterior sheath) in 66 rectus
      abdominis mm. from 33 cadavers among them: 1) 52 "large" perforators were over
      1.0 mm in diameter; 2) 107 "suitable" perforators ran parallel to the muscle
      fibers without giving off large muscular branches; and 3) 35 "ideal" perforators
      combined these characteristics. The ideal perforators were usually located in the
      mid-abdominal region, 10-30 mm lateral to the umbilicus. The suitable perforators
      were usually present, often in combination with the ideal perforator(s), in a
      restricted area 20 mm cranial and 40-50 mm lateral to the umbilicus. We
      classified the course and ramification pattern of the deep inferior epigastric a.
      into six patterns, depending on whether the anastomosis was sited in the medial
      or lateral branch and the level at which the branches originated.

PMID- 11963620
TI  - Spontaneous reanastomosis between lymphatic vessels following syngeneic
      transplantation of the small intestine in the rat.
AB  - Spontaneous lymphvascular reanastomosis (SLR) following small bowel
      transplantation in rats is of clinical relevance for the resorption of long chain
      fatty acids. Detailed morphological and molecular data concerning the process of
      lymphvascular reanastomosis are not available in the literature. In this study
      SLR was investigated using microradiology and scanning electron microscopy.
      Between the 8th and 21st postoperative days following transplantation SLR does
      not occur between the intestinal trunk of the transplant and the thoracic duct of
      the recipient. Instead, an indirect connection was observed between the inserted
      advential lymphatic vessels of the mesenteric artery and lymphatic vessels of the
      aorta or ductus deferens, which are connected with the thoracic duct.

PMID- 11963622
TI  - Material properties of trabecular bone structures.
AB  - The transplantation of human allograft for restoration and filling of cortical
      bone defects is well known. Our aim was an experimental investigation of the
      mechanical stability of the often used femoral head spongiosa depending on the
      caliber and extent of the allograft. To evaluate the orientation of the
      trabecular structures of the femoral head and relate this data to its mechanical
      properties, morphometric studies were combined with mechanical tests of
      cancellous bone specimens. The mechanical examination of the allograft was done
      following the compression test according to DIN 50106. We examined 36 human
      unfixed hip joint spongiosa cylinders with a height of 11 mm and a diameter of 24
      mm. We took three specimens from each femoral head. We compressed the allograft
      at a constant velocity of 0.017 mm/sec. We calculated the maximum compression
      strength, the yield point and the Young's modulus. We also examined 12
      parallelepipedic specimens with (17 x 17 x 51 mm) for morphometric analysis and
      loading in the direction of the primary compressive group (PCG), as well as
      perpendicular loading and at an angle of 45 degrees. We found divergent
      mechanical stabilities. None of the femoral heads showed comparable compressive
      strength. There was no position dependency of the strength of the samples. No
      relation between optical appearance and strength was found. We found a value for
      the lower compressive strength, which can be used for calculation as a basic
      value for safe constructions. Furthermore we tested the well known dependence of
      strength on the direction of the trabecular structure. We found a strong
      relationship between strength and load direction on the preferred direction of
      the trabecular structure. The sole recommendation resulting from our
      investigations is to rely on the lowest compressive strength for all preoperative
      planning. Relying on higher compressive strength by using the theoretical
      predicted areas of higher strength is hazardous since we found no correlation
      between position of sampling and strength. The size of our samples is important,
      because of the fact that different sizes of the samples might cause different
      failure mechanisms in the samples. The preparation of the femoral head spongiosa
      should be done according to the primary compressive group of the trabecular
      structure.

PMID- 11963621
TI  - Functional anatomy of the human temporal muscle.
AB  - The authors carried out an anatomical and magnetic resonance imaging study on the
      architecture of the mandibular elevator muscles of 169 cadavers. The aim of the
      study was to define the organisational architecture of the human masseter,
      temporal and pterygoid muscles. Layer by layer dissection and anatomical cuts in
      different spatial planes showed that the temporal muscle has a different
      architecture to the other mandibular elevator muscles. Indeed this muscle does
      not have the pennate structure of the masseter and pterygoid muscles. Through
      electromyographic study the behavior of this muscle allowed the establishment of
      its functional segmentation during the masticatory cycle. Our study showed three
      distinct anatomical portions in the middle of the temporal muscle which
      correspond to this functional classification. The MRI study confirmed the results
      of our anatomical study.

PMID- 11963623
TI  - Corpus callosum: microsurgical anatomy and MRI.
AB  - The anatomy of the corpus callosum has received renewed interest during recent
      years due to the increasing number of callosotomies performed to treat
      intraventricular lesions, as well as some forms of generalized epilepsy. We have
      previously reported on the microsurgical anatomy of the corpus callosum and
      identified specific anatomical reference landmarks that can be used during
      surgery. In the present study we have continued the anatomical aspect of this
      earlier work in a larger number of cases, with in vitro observations (brain out
      of skull) being compared with the corresponding in vivo features seen in sagittal
      MRI slices. Fifty-three in vitro microsurgical callosotomies was performed and
      the data collected compared with a series of 57 in vivo normal MR callosal
      images. Callosal dimensions were measured on both the anatomical and MRI
      material, thus overcoming the problems associated with in vitro callosal
      deformation. Of the anatomical landmarks studied the distance from the genu of
      the corpus callosum to the bifurcation of the columns of the fornix was found to
      be useful for the intraoperative evaluation of the extent of rostral callosotomy,
      as it is not significantly changed in in vitro. The main microsurgical features
      of rostral callosotomy are presented.

PMID- 11963624
TI  - Lumbar spinal ganglia enhancement after gadolinium chelate administration: a
      radio-histological correlation.
AB  - The aim of the present study was to assess the frequency of enhancement of lumbar
      spinal ganglia after Gadolinium chelate injection in patients without
      radiculopathy, and to correlate the enhancement with histology. This study is
      based on the analysis of MR lumbar examinations conducted on 18 patients without
      radicular symptoms, or previous surgery of the lumbar spine, or disease of the
      nervous system. The patients were imaged with a 1.5 T unit. Sagittal images were
      first obtained with a T1-weighted turbo spin-echo. Axial and sagittal images were
      then obtained with a T1-weighted turbo spin-echo, fat-saturated sequence after
      Gadolinium intravenous injection from the T12/L1 to the L5/S1 level. All 180
      spinal ganglia demonstrated an important and homogeneous enhancement after
      Gadolinium injection. Four spinal ganglia obtained by dissection from four
      different fresh cadavers were studied by light microscopy to determine the
      potential relationship between contrast enhancement and presence and topography
      of vessels within the spinal ganglia. Vessels were particularly abundant at the
      peripheral zone of the spinal ganglia. The post-contrast enhancement of the
      spinal ganglia after Gadolinium administration has to be known and may be
      explained by the microvasculature pattern.

PMID- 11963625
TI  - Variations of the position of the colon as applied to percutaneous nephrostomy.
AB  - The widespread and increasing usage of percutaneous nephrostomy procedures makes
      an awareness of the anatomical variations of the colon in relation to the kidney
      essential. Injury to the colon during this procedure is associated with
      significant morbidity. The aim of this study was to determine the relation of the
      colon to the insertion line used during a percutaneous nephrostomy and therefore
      determine whether the colon is at risk of injury. 333 CT-scans taken in a supine
      position were studied in order to determine the position of both the ascending
      and descending colon to the percutaneous nephrostomy insertion line on the level
      of the superior pole, hilum and inferior pole of the kidneys. In the majority of
      cases, the ascending and descending colon lie anterior to the line of insertion,
      and were therefore not at risk. However the descending colon was found to be at
      risk in 16.1% of cases and the ascending colon in 9.0% of cases on the level of
      the inferior pole of the kidney. The risk was significantly lower on the level of
      the hilum and superior pole of the kidneys on both sides. Age distribution
      analysis showed that the colon is rarely at risk under twenty years of age and
      the highest risk being in the age range above 40 years. Adequate radiographic
      evaluation is essential before performance of percutaneous nephrostomy
      procedures, especially to evaluate the position of the colon as related to the
      inferior poles of the kidneys.

PMID- 11963626
TI  - Bahren types III and IVa testicular vein anomalies as a reason for failure in
      left idiopathic varicocele retrograde sclerotherapy. Ontogenic discussion and
      clinical implications.
AB  - Left testicular vein anatomy has received more attention due to the presence of
      competent or incompetent venous valves and bypassing anastomoses, which are
      involved in venographic diagnosis and embolisation of varicocele. The left
      gonadal vein develops, in both males and females, between the 5th and 7th
      intrauterine weeks, being derived from the distal or postrenal portion of the
      left subcardinal vein. The varicocele aetiologic hypothesis leads to ontogenetic
      disturbances in the development of the secondary venous system. Retrograde
      testicular venography shows the precise anatomy of the left pampiniform plexus,
      while anterograde testicular venography identifies the presence of the valve and
      possible continence. In the present case sclerotherapy could not be achieved due
      to testicular vein anomalies. Sclerotherapy versus surgical high ligature of the
      left testicular vein in cases of left idiopathic varicocele with testicular vein
      anomalies is discussed.

PMID- 11963627
TI  - Hepatomesenteric trunk.
AB  - An hepatomesenteric trunk, formed by the common hepatic and superior mesenteric
      arteries, was found in a 50-year-old male cadaver. The left gastric and splenic
      arteries arose as a common trunk, the gastrosplenic trunk, from the abdominal
      aorta; no typical celiac trunk was present. In addition, the hepatomesenteric
      trunk passed posterior to the portal vein. A knowledge of variations of the
      common hepatic artery may be important in pancreaticoduodenectomy, as well as
      during hepatic artery infusion chemotherapy.

PMID- 11963628
TI  - Annular pancreas in adults: embryological development, morphology and clinical
      significance.
AB  - Three cases (two male, one female) of annular pancreas are presented, which were
      found and operated on within the last three decades. Diagnosis was made using
      imaging techniques, especially ultrasonography and computed tomography. In two
      cases there was incomplete obstruction, while in the other obstruction was
      complete. It is characteristic that in the case of complete obstruction the
      annular portion of the pancreas attached to a circular band of connective tissue,
      while in the two cases of incomplete obstruction there was a complete ring of
      pancreatic tissue. In all cases surgical intervention was needed in order to
      create a bypass. In the first case gastroenterostomy and truncal vagotomy was
      performed, in the second latero-lateral duodeno-jejunostomy and in the third
      latero-lateral antropyloroduodeno-jejunostomy. The embryology and morphology of
      the annular pancreas, the morphology of its duct system, diagnosis, differential
      diagnosis and the surgical treatment of this rare condition are reviewed.

PMID- 11963630
TI  - [Hematologic etiology of thromboembolic disease].

PMID- 11963629
TI  - Anomalous veins of the retroperitoneum: clinical considerations.
AB  - A case of complex anomalies (variations) of the veins of the retroperitoneum in a
      57 year old male cadaver is presented. The anomaly involved a double inferior
      vena cava, with the left suprarenal v. draining into the left vena cava and the
      right testicular v. drained into the right renal v.. There was also no left
      common iliac v., with the left external iliac v. draining into the left vena cava
      and the left internal iliac v. into the right common iliac v.. Although
      duplication of the inferior vena cava has previously been reported the present
      case is interesting because of the complexity of the associated anomalies.

PMID- 11963631
TI  - [Assessing professional training].
AB  - This article is intended as a contribution to the current debate on assessment of
      clinical competence during the clerkship phase of the undergraduate medical
      training programme. Assessment in clinical clerkship typically concerns the final
      stage of undergraduate medical training. When clinical competence is split up
      into numerous attributes and different methods are used for each attribute, an
      atomistic approach may be the result. At the end of a curriculum, such as with
      clerkship assessment in particular, we want to assess the integrated performance
      of clinical tasks, Splitting up tasks into different attributes and testing these
      separately will arm the authenticity of the assessment. The emphasis in clerkship
      assessment must be on the formative role of assessment. The popular objective
      structured clinical examination (OSCE) uses direct observation of students in
      simulated clinical situations under standardized conditions. The assessment,
      however, remains limited to the shows how. There is a wide gap between the
      educational objectives and the assessment of clerkship training. Finally, in
      modern undergraduate medical curricula increasing value is placed on teaching and
      teacher training. Supervision can be provided in a variety of styles and
      settings. The final assessment of the clerkship is determined by a combination of
      tests. These effects should be monitored continuously to ensure that students are
      given the opportunity and are being encouraged to achieve the educational
      objectives the clerkship is intended to provide. The clerkship as an educational
      environment is gradually receiving more attention. In light of the above findings
      and the importance of clerkship to medical education, improvements can and must
      be made.

PMID- 11963632
TI  - Circadian rhythm of hunger sensation in patients affected by dysthymic disorder.
AB  - PURPOSE: The present study investigates the daily pattern of hunger sensation
      (HS), namely orexia, in patients affected by "Dysthymic Disorder" (DD). The aim
      is to detect whether there are changes in the circadian rhythm (CR) of HS, herein
      investigated as a "marker rhythm", that can reveal a dysfunction of the
      "circadian biological clock" (CBC). In such a circumstance, one could be
      authorised to suggest a resynchronizing therapy, via antidepressant chronizing
      drugs and/or morning exposure to bright light, as it is currently done in other
      types of human depression, having a documented dysfunction of the CBC. MATERIALS
      AND METHODS: Volunteered with informed consent for the study 6 women (age = 34-56
      years; mean BMI = 22.7 +/- 4.8 kg/m2) affected by DD. 10 clinically healthy women
      (CHW, age = 21-52 years; mean BMI = 24.0 +/- 0.5 kg/m2) were recruited as the
      controls. Both of the dysthymic patients (DP) and CHW were asked to compile the
      "orexigram", which was chronobiometrically analyzed by means of the 1.
      conventional statistical methods; 2. rhythmometric analysis for the CR; 3.
      spectral analysis for the harmonic components of the orexigram. RESULTS: The DP
      were found to be characterized by a normal daily level of HS, with 1. the CR of
      the orectic stimulus to be preserved and well located in its acrophase, and 2.
      the spectrogram of the orexigram to be substantially well configured.
      CONCLUSIONS: The above-cited results suggest that the DP show no alterations in
      the HS marker rhythm that can be taken as an evidence for declaring that the DD
      is not characterized by a relevant dysfunction of the CBC. Lacking in particular
      a phase-shift in HS marker rhythm, it can be argued that the DD is an affective
      disorder for which a resynchronizing therapy (exposure to bright light or
      pharmacological chronizers) seems to be "a priori" not indicated.

PMID- 11963633
TI  - [Non-traumatic rhabdomyolysis: clinical and laboratory diagnosis, assessment of
      renal complications].
AB  - PURPOSE: Non traumatic rhabdomyolysis (RML) is an infrequent and sometimes
      clinically silent syndrome. RML incidence is increasing in the last few years. A
      prospective study was performed: 1) to value the non traumatic RML incidence in
      patients admitted to Emergency Room; 2) to reevaluate the clinical and laboratory
      criteria of diagnosis; 3) to establish complications' incidence and prognosis
      during the recovery. PATIENTS AND METHODS: In Emergency Medical First Aid 15.301
      patients were examined. To the study were admitted only patients having CK level
      grater than fivefold the upper normal limits and without trauma, recent surgery,
      heart and cerebral disease. RESULTS: During the six months study, non traumatic
      RML incidence was 0.1% (16 patients of 15.301). Drugs, alcohol and substance
      abuse acute intoxication were the commonest causes. The Acute Renal Failure (ARF)
      was the more frequent complication (9 patients of 16). Four patients of nine was
      treated only by fluid administration, the other five by dialysis. Oligoanuric-ARF
      appeared only in patients affected by toxic RML. These patients had no-return to
      normal renal functional values at the time of hospital discharge. CONCLUSIONS:
      Non traumatic RML should be take into account by emergency doctor in cases of
      acute intoxication. To prevent the complications it's necessary the right
      interpretation of clinical and laboratory datas and an early and adequate
      therapy.

PMID- 11963635
TI  - [27th National Congress of Oncology of the Italian Tumor Society. November 21-23,
      2001, Rome. Part I].

PMID- 11963634
TI  - [Rationale for the use of renin-angiotensin inhibitors in the treatment of
      arterial hypertension and correlated organ damage].
AB  - The treatment of hypertension has evolved in recent years. Blood pressure
      lowering per se is no longer a sufficient parameter to evaluate its beneficial
      effects on end-organ damage. Drugs must be considered on the basis of their
      effects on cellular level and structural alterations that occur in the
      vasculature, heart and kidney. Angiotensin converting enzyme inhibitors and
      angiotensin II receptor blockers, two classes of drugs that inhibit angiotensin
      II effects, may protect target organs from damage and thereby improve outcomes.
      The mechanisms of action are different even if both counteract all noxious
      effects of angiotensin II. Angiotensin II receptor blockers selectively inhibit
      AT1 receptors whose stimulation mediates the hypertensive and proliferative
      effects of angiotensin II while do not interfere with AT2 receptors. These last
      ones have a role not well established but it has been postulated that they have
      antihypertensive and antiproliferative effects. A review will be made on the
      cellular mechanisms of angiotensin II activity and the effects of AT receptor
      antagonists.

PMID- 11963636
TI  - [Alcoholic hepatopathy].
AB  - OBJECTIVES: To extensively discuss clinical features, laboratory data and
      pathology findings associated with alcoholic hepatitis as well as the new
      insights into pathogenesis and the appropriate therapy. DESIGN: Review of current
      literature. RESULTS: Acetaldehyde gives rise to neoantigens by complexing with
      various proteins, which, in turn, favors the appearance of autoantibodies.
      Antibodies against the hepatic lipoprotein and a number of hepatocyte surface
      glycoproteins have been detected in alcoholic hepatitis. Experimental studies
      have shown that acetaldehyde and malonyldialdehyde form highly immunogenic
      aggregates (MAA adducts). Antibody titers are usually higher in patients with
      more advanced disease, which argues for a major etiologic role. HLA antigens such
      as B8, DR3, DR4, which are usually associated with autoimmune diseases, are more
      frequently observed in alcoholic hepatitis patients. CONCLUSIONS: Despite the
      above, it is still questionable whether alcoholic hepatitis pathogenesis is
      autoimmune in origin. Why do only 15-20% of subjects who have long been abused
      alcohol develop hepatitis? What are the predisposing factors? What events trigger
      the immunologic reactivity? If MAA adducts play a role, why are not all the
      alcohol abusers affected by hepatitis? Transplantation outcome in well selected
      patients with alcoholic hepatitis is as good as--or even better than--the one
      reported for patients with different types of hepatitis.

PMID- 11963637
TI  - [Efficacy-safety relationship of AT1 angiotensin II receptor antagonists: current
      data].
AB  - In evolution of hypertension's treatment it may no be sufficient to lower blood
      pressure to achieve beneficial effects in long term outcomes. Several goals of
      antihypertensive treatment remain unrealized. There is so great interest for new
      drugs that may protect target organs and improve outcomes. The angiotensin II,
      the major effector of the renin-angiotensin-aldosterone system, causes a variety
      of potentially noxious cardiovascular effects which are specially mediated by AT1
      subtype receptors. AT1 receptor blockers (losartan, candesartan, irbesartan,
      valsartan) are available drugs in the angiotensin-II-antagonist class. This paper
      examine the peculiar features of this new class of drugs.

PMID- 11963638
TI  - [A 74-year-old woman with macrocytic anemia].
AB  - A seventy-four years old woman is assessed for asthenia, fatigue, non ulcerous
      dyspepsia with macrocytic anemia. The patient's medical history taking in
      Binswanger disease--diagnosed 5 aa before-, epilepsy-2 aa before- and a previous
      episode of TVP of the left leg, suggested the hypothesis that a B12 deficiency,
      by a chronic gastritis, would involve an increase of homocysteine cause of the
      clinical manifestations of megaloblastic anemia, Binswanger disease, tardive
      epilepsy and previous TVP. The fisic and blood and instrumental exams confirmed
      the clinical diagnosis. The patient is having vitamin B12.

PMID- 11963639
TI  - [The "petit papier": a clinical sign that should not be underestimated].
AB  - The Authors report two cases in which the sign of the "petit-papier" gives
      interesting question for a correct management of the patients in which the
      somatoform disorders is often the bulklt background of an organic illness.

PMID- 11963640
TI  - [Physiologic and therapeutic importance of serotonin and the serotonergic
      system].
AB  - Serotonin (5-hydroxytryptamine, 5-HT) induces various effects in the central
      nervous system, cardiovascular system and gastrointestinal tract. The response
      depends primarily on the nature of the 5-HT receptors involved. In the light of
      the current knowledge about the anatomy and physiology of the serotonergic system
      and the distribution of the various 5-HT receptors in the organs and tissues, the
      established and potential therapeutic applications of 5-HT receptor ligands in
      the treatment of several disorders are discussed. In particular, new selective 5
      HT receptor ligands influencing intestinal motility and pain perception such as
      the partial 5-HT4 receptor agonist tegaserod appear promising for a more specific
      treatment of irritable bowel disease.

PMID- 11963641
TI  - Interaction potential of lercanidipine, a new vasoselective dihydropyridine
      calcium antagonist.
AB  - Using some calcium channel blockers of the dihydropyridine-type (amlodipine (CAS
      88150-42-9, felodipine (CAS 72508-76-3), lercanidipine (CAS 100472-26-7),
      nifedipine (CAS 21829-25-4), nitrendipine (CAS 39562-70-4)) as example the
      interaction potential of these substances will be compared in terms of affecting
      metabolism and transport of drugs. The cytochrome P450 (CYP) isoform CYP3A4 and
      the P-glycoprotein (P-gp), respectively, will have a high impact for both
      pharmacokinetic processes, as all 5 calcium channel blockers are substrates of
      CYP3A4 and in addition nifedipine, nitrendipine and felodipine represent
      inhibitors of P-gp, which can cause an increase in the plasma levels of digoxin
      (model substrate of P-gp). If inducers (e.g. rifampicin, anticonvulsants, St
      John's wort) or inhibitors (ketoconazole, itraconazole, erythromycin,
      clarithromycin, nefazodone, fluvoxamine, fluoxetine, sertraline, ritonavir,
      indinavir, amprenavir, saquinavir or grapefruit juice) of CYP3A4 are
      concomitantly administered pharmacokinetic interactions could be expected to a
      variable extent. Some alternative drugs are mentioned which will not affect
      CYP3A4. In addition to these putative pharmacokinetic interactions also
      pharmacodynamic interactions with other cardiovascular active substances might be
      considered and some caution should be exercised if vasodilators are given as
      comedication.

PMID- 11963642
TI  - General pharmacological profile of the novel muscarinic receptor agonist SNI
      2011, a drug for xerostomia in Sjogren's syndrome. 3rd communication: effects on
      respiratory and cardiovascular systems.
AB  - A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3
      oxathiolane- 5,3'-quinuclidine]monohydrochloride hemihydrate, cevimeline, CAS
      153504-70-2), is a candidate therapeutic drug for xerostomia in Sjogren's
      syndrome. The general pharmacological properties of this drug on the respiratory
      and cardiovascular systems were investigated in guinea pigs and dogs. SNI-2011
      reduced the contractile force and beating rate of isolated right guinea pig
      atrium at 1 x 10(-6) mol/l or higher and 3 x 10(-6) mol/l or higher,
      respectively. SNI-2011 reduced the contractile force of isolated left atrium
      induced by electric stimulation at 1 x 10(-6) mol/l or higher. In anesthetized
      dogs, SNI-2011 caused a transient decrease in blood pressure, tachycardia and an
      increase in femoral arterial blood flow at 0.01 mg/kg i.v. or higher. At 1 mg/kg
      it caused continuous bradycardia, a decrease in femoral arterial blood flow and
      an increase in respiration rate in addition to the changes observed immediately
      after injection. A transient negative T-wave was observed as the only change in
      the ECG immediately after injection at 1 mg/kg. However, when SNI-2011 was
      injected intraduodenally, a decrease in femoral arterial blood flow, bradycardia
      and a tendency to increase respiration rate were observed at doses of 1 to 3
      mg/kg. All these events in dogs were antagonized by atropine. These results
      suggest that oral administration of SNI-2011, that is the clinical administration
      route, can distinctly reduce the muscarinic effects on the respiratory and
      cardiovascular systems compared to intravenous administration.

PMID- 11963643
TI  - Neuroprotective activity of a nanoparticulate formulation of the glycineB site
      antagonist MRZ 2/576 in transient focal ischaemia in rats.
AB  - The objective of the present study was to characterise the neuroprotective
      activity of the novel glycineB site NMDA (N-methyl-D-aspartate) receptor
      antagonist MRZ 2/576 (8-chloro-4-hydroxy-l-oxo- 1,2-dihydropyridazino[4,5
      b]quinolin-5-oxide choline salt, CAS 202807-80-5) in a rodent model of focal
      cerebral ischaemia. Since the solubility of MRZ 2/576 at a physiological pH, is
      minimal and adequate concentrations can be achieved only at relatively high basic
      pH the in vivo use of the substance is substantially limited. Therefore, a
      special nanoparticle formulation was developed to provide means for lengthy i.v.
      administration of experimentally relevant doses within the physiological range of
      pH. Focal ischaemia of 75 min duration was induced in rats by a reversible
      occlusion of the middle cerebral artery (MCAo). MRZ 2/576 (18 mg/kg over 10 min
      followed by 18 mg/kg/h over 6 h) or placebo treatment was initiated immediately
      after onset of MCAo. Neurological deficit was evaluated daily for 3 consecutive
      days and then brain infarct analysis was performed. MRZ 2/576 significantly
      improved the neurological score at 24 h and 72 h post stroke (p < 0.05 vs.
      placebo). It also produced a 53.0% reduction of total infarct size, 60.4% of
      cortical and 42.3% of striatal infarction (p < 0.05 vs. placebo). Temporary drug
      induced hypothermia and ataxia were observed during infusions. This leads to the
      conclusion that prolonged administration of the glycineB site antagonist MRZ
      2/576 in form of the nanoparticle suspension ameliorates ischaemic damage induced
      by the transient MCAo in rats. The results suggest that nanoparticles hold
      promise as an effective strategy e.g. for substances with physico-chemical
      characteristics that otherwise would preclude them from pre-clinical development
      and/or clinical application.

PMID- 11963644
TI  - Study of the novel non-xanthine heterocyclic compound GU285 as a potent non
      selective adenosine receptor antagonist in the rat.
AB  - The novel pyrazolo[3,4-d]pyrimidine compound GU285 (4-amino-6-alpha
      carbamoylethylthio-1- phenylpyrazolo[3,4-d]pyrimidine, CAS 134896-40-5) was
      examined for its ability (1) to inhibit binding of adenosine (ADO) receptor
      ligands in rat brain membranes, (2) to antagonise functional responses to ADO
      agonists in rat right and left atria and coronary resistance vessels, and (3) to
      reduce the fall in heart rate and arterial blood pressure produced by the ADO A1
      agonist N6-cyclopentyladenosine (CPA) in the intact, anaesthetized rat. GU285
      competitively inhibited binding of the ADO A1 agonist [3H]-R-N6
      phenylisopropyladenosine (R-PIA) yielding a Ki value of 11 (7-18) nmol.l-1
      (geometric mean +/- 95% Cl). When assayed against the ADO A2A selective agonist
      [3H]-2-[p-(2-carboxyethyl)- phenethylamino]-5'-N-ethylcarboxamidoadenosine,
      (CGS21680), a Ki of 15 (10-24) nmol.l-1 was obtained. In spontaneously beating
      right atria, GU285 competitively antagonized negative chronotropic effects of R
      PIA with a pA2 of 8.7 +/- 0.3 and in electrically paced left atria, GU285
      competitively antagonized negative inotropic effects of R-PIA with a pA2 of 9.0
      +/- 0.1. In the potassium-arrested, perfused rat heart GU285 (1 mumol.l-1)
      antagonized only the high sensitivity, ADO A2B mediated component of the biphasic
      relaxation of the coronary vasculature produced by NECA. The low sensitivity
      component was unchanged. GU285 (1 mumol.kg-1) antagonized the negative
      chronotropic and hypotensive effects of the adenosine A1 agonist CPA in
      anaesthetized rats, producing a 10-fold rightward shift in the dose-response
      relationship. These data demonstrate that in the rat, GU285 is a potent, non
      selective adenosine receptor antagonist that maintains its activity in vivo.

PMID- 11963645
TI  - Evaluation of the bioequivalence and pharmacokinetics of two tablet formulations
      of isosorbide-5-mononitrate after single oral administration in healthy
      volunteers.
AB  - The pharmacokinetic parameters of two oral formulations of 20 mg tablets of
      isosorbide-5-mononitrate (CAS 16051-77-7, Dilavenil as test and another
      commercially available preparation as reference) were compared in an open-label,
      randomized, single oral dose, two-period cross-over design in 20 healthy
      volunteers under fasting conditions. Plasma concentrations of isosorbide-5
      mononitrate were measured by a validated gas chromatographic assay. The
      parametric 90% confidence intervals of the geometric mean values of the
      test/reference ratios were 101.2% to 108.5% (point estimate: 104.7%) for AUC0
      variation of, 101.6% to 110.7% (point estimate: 106.2%) for AUC0-t, and 98.1% to
      115.5% (point estimate: 106.1%) for Cmax, within the acceptance criteria for
      bioequivalence (80%-125%). Tmax values were analyzed by the nonparametric
      Wilcoxon test and the difference was not statistically significant. Therefore, it
      is concluded that the test and reference isosorbide-5-mononitrate formulations
      are bioequivalent for both the extent and the rate of absorption.

PMID- 11963646
TI  - Pharmacokinetic behaviour of antithrombin III following intravenous infusion in
      healthy volunteers.
AB  - Antithrombin III (CAS 52014-67-2) is produced from plasma of healthy donors and
      is purified from any detectable agent of transmissible infection. This drug is
      used in therapy by i.v. route to manage acute thrombotic episodes and to treat
      patients suffering from its deficiency. The present trial was conducted with the
      aim to evaluate the pharmacokinetics and the safety of a new preparation of
      antithrombin III, which in the purification procedure has included a
      nanofiltration step to increase the safety against the transmission of any agent
      of infection. The trial was conducted in twelve healthy volunteers of either sex.
      All the ethics procedures were fully respected, namely the approval from Ethics
      Committee, the notification to the central regulatory authority, the approval of
      consent form in writing. Volunteers were hospitalized about 36 h before drug
      treatment. The baseline situation was investigated throughout the day before the
      treatment (day-1). On day 1, the drug was infused i.v. for 20 min. Twenty blood
      samples were drawn from each volunteer, in baseline situation, during and after
      the infusion. Functional antithrombin III, antithrombin III antigen, prothrombin
      time, partial thromboplastin time were evaluated in all plasma samples. Both
      functional antithrombin III and antithrombin III antigen produced well defined
      plasma concentration-time profiles after the infusion, which allowed net values
      of these two analytes to be obtained subtracting baseline from post-infusion
      concentrations. Net pharmacokinetic parameters of functional antithrombin III and
      antithrombin III antigen proved to be almost superimposable. A comparison of data
      obtained in this trial on healthy volunteers with those previously obtained by
      other authors on target population demonstrates similar and fully comparable
      results. The authors conclude that the nanofiltration step neither affects at all
      the pharmacokinetics/pharmacodynamics nor the safety of the formulation
      investigated.

PMID- 11963648
TI  - Randomised crossover studies of the bioequivalence of two fenofibrate
      formulations after administration of a single oral dose in healthy volunteers.
AB  - Bioequivalence of a newly developed semi-solid formulation (Lidose) of
      fenofibrate (CAS 49562-28-9), and a reference, micronized formulation of
      fenofibrate was investigated in two randomised, open-label clinical studies with
      a crossover design. Both studies involved two distinct groups of 24 healthy
      volunteers. Doses of 67 mg and 200 mg, respectively, were used in study 1 and
      study 2. On day 1, a single oral dose was administered to all subjects, using one
      of the two formulations to be compared. Single oral dosing with the other
      formulation occurred after a washout period of at least 8 days. Blood samples
      were taken after each dosing for measurement of plasma fenofibric acid
      concentrations by high-performance liquid chromatography (HPLC) combined with
      fluorescence detection, and plasma pharmacokinetic parameters were determined. No
      statistically significant differences were noted for Cmax, Tmax, AUC0-t and AUC0
      variation of between subjects treated with the new formulation and those
      receiving the reference formulation. Side effects were mild and not significantly
      different between the two fenofibrate preparations. These two studies based on
      validated methods demonstrate that the new and the reference fenofibrate
      formulations are bioequivalent when administered at the two doses studied.

PMID- 11963647
TI  - Local anaesthetic properties of ambroxol hydrochloride lozenges in view of sore
      throat. Clinical proof of concept.
AB  - Acute oro-pharyngeal catarrh is characterised by mild to severe sore throat, such
      as pain on swallowing, feeling of scratchiness, burning and urge to cough. The
      present study was conducted to explore whether the test compound is going to show
      clinical relevance and is a suitable medication for the relief of these symptoms.
      OBJECTIVE: Description and comparison of the efficacy and tolerability of
      lozenges containing 20 mg ambroxol hydrochloride (trans-4-[(2-amino-3,5
      dibrombenzyl)amino]cyclohexano hydrochloride, CAS 18683-91-5) in relieving acute
      sore throat, in comparison to placebo. DESIGN: Multi-centre, prospective, placebo
      controlled, randomised, double-blind trial involving two days of treatment with
      up to 6 lozenges containing 20 mg ambroxol hydrochloride per day. SUBJECTS: Two
      hundred-eighteen (218) patients were enrolled (97 males, 121 females, average
      age: 39.4 +/- 15 years, range: 17-81 years); 215 were treated: 107 with 20 mg
      ambroxol and 108 with placebo; 26 discontinued prematurely (13 in each treatment
      group). 208 patients constituted the intent-to-treat (ITT) dataset (105 and 103
      for treatment with ambroxol and placebo, respectively); 196 patients constituted
      the perprotocol (PP) dataset (97 and 99, respectively); all treated patients were
      part of the dataset for safety analysis. TREATMENTS: Double-blind treatment with
      up to 6 lozenges per day containing 20 mg ambroxol hydrochloride or placebo (a
      lozenge with a distinct minty flavour). MAIN OUTCOME MEASURES: The time-weighted
      average pain relief over the first 3 h after the first lozenge as a ratio of the
      baseline pain intensity of sore throat (SPIDnorm) and the patients' evaluation of
      efficacy and tolerability at the end of each day of treatment. RESULTS: Both
      treatments led to a reduction of pain intensity; the mean (+/- SD) SPIDnorm after
      the 1st lozenge were 0.39 +/- 0.27 and 0.28 +/- 0.25 for 20 mg ambroxol
      hydrochloride and placebo, respectively; the treatment effect of ambroxol was
      statistically significantly superior compared to placebo (p: 0.0029; 95%
      confidence interval estimate of the mean treatment difference for ambroxol minus
      placebo: 0.04 to 0.18). At the end of each subsequent ambulatory treatment day
      with up to 6 lozenges per day, a statistically significantly higher proportion of
      patients scored a higher level of efficacy for the active treatments with
      ambroxol hydrochloride compared to placebo. The investigational treatments were
      equally well tolerated. CONCLUSIONS: Sucking lozenges containing 20 mg ambroxol
      hydrochloride has a beneficial pain relieving effect in patients with acute sore
      throat, superior to that which otherwise can be achieved by sucking a placebo
      lozenge. This finding confirms that the preclinical local anaesthetic properties
      of ambroxol hydrochloride may have beneficial clinical implications.

PMID- 11963649
TI  - Nitric oxide release from coumarin 4-carboxamidoximes in the presence of thiols.
AB  - Coumarin 4-carboxamides with potent anti-inflammatory activity were studied for
      nitric oxide release in the presence of thiol cofactors in vitro. It was found
      that NO2- release was dependent on the nature of thiol.

PMID- 11963650
TI  - [Registration of drug-associated lesions of the mucosa of the upper
      gastrointestinal tract. The problem of characterizing the health status of
      healthy subjects].
AB  - BACKGROUND AND AIM: Investigations with regard to toxic effects of drugs on the
      upper gastrointestinal tract depend on healthy volunteers with normal mucosal
      conditions. Because of the high prevalence of Helicobacter pylori infection it is
      mandatory to exclude infected volunteers without abdominal history as early as
      possible. This study was to compare the power of non-invasive and invasive tests
      in the selection of volunteers without gastric disease. METHOD: 85 healthy
      volunteers (age 18-35 years) without abdominal history underwent both
      gastroduodenoscopy and specific tests for Helicobacter pylori infection (IgA- and
      IgG-antibodies, ureasetest, culture, HE-staining). In the case of pathological
      findings, the biopsies were performed without including the subjects into the
      study with a non-steroidal anti-inflammatory drug (NSAIDs) (Diclofenac, CAS 15307
      86-5). The invasive tests of volunteers, who were selected, were performed at the
      end of drug period, because biopsies would influence the outcome of a 7-day
      treatment with diclofenac RESULT: Initially 25/85 volunteers without any history
      of abdominal disease must be excluded. In 15 subjects there were abnormal
      concentrations of IgG- and/or IgA- antibodies against Helicobacter pylori.
      Endoscopically in 10 persons severe lesions were found (6 ulcer and/or erosions
      and/or reflux disease). In 18 subjects histologically the Helicobacter pylori
      infection was confirmed. At the end of the treatment period in 17/60 volunteers a
      positive Helicobacter pylori staining was found. Comparing five Helicobacter
      pylori tests there were no significant correlations between non-invasive and
      invasive procedures. CONCLUSION: The endoscopic investigation
      (gastroduodenoscopy) was the only valid method to differentiate between healthy
      volunteers and subjects with mucosal lesions. With regard to Helicobacter pylori
      infection neither the non-invasive nor the invasive tests were significantly
      correlated. Therefore, in investigations on the toxic effect of drugs the
      infection rate must be determined after treatment to prove the homogeneity of and
      between the groups. Most important is a subtile endoscopic technique which
      depends on high resolution video-endoscopes, chromoscopy as well as inter- and
      intra-observer variation procedures.

PMID- 11963651
TI  - Technical advances and pitfalls on the way to human cloning.
AB  - There exists a widespread consensus that the cloning of human beings to term
      would be detrimental to both the mother and child and of little value to society.
      However, the ambition of a few organisations and the recent advances in cellular
      and molecular technologies that led to the cloning of Dolly the sheep, for
      example, have meant that such a procedure will be possible if not illegal in the
      near future. The science associated with the cloning technologies practiced in
      other mammalian species reported to date provide important advances in our
      understanding of how cells function during early developmental processes and
      commit themselves to specific developmental pathways. However, many technological
      insufficiencies remain. Both technological advances and several of the associated
      insufficiencies are outlined in this review.

PMID- 11963652
TI  - The emerging roles of translation factor eIF4E in the nucleus.
AB  - The emerging field of nuclear eIF research has yielded many surprises and led to
      the dissolution of some dogmatic/ideological viewpoints of the place of
      translation in the regulation of gene expression. Eukaryotic initiation factors
      (eIFs) are classically defined by their cytoplasmic location and ability to
      regulate the initiation phase of protein synthesis. For instance, in the
      cytoplasm, the m7G cap-binding protein eIF4E plays a distinct role in cap
      dependent translation initiation. Disruption of eIF4E's regulatory function
      drastically effects cell growth and may lead to oncogenic transformation. A
      growing number of studies indicate that many eIFs, including a substantial
      fraction of eIF4E, are found in the nucleus. Indeed, nuclear eIF4E participates
      in a variety of important RNA-processing events including the nucleocytoplasmic
      transport of specific, growth regulatory mRNAs. Although unexpected, it is
      possible that some eIFs regulate protein synthesis within the nucleus. This
      review will focus on the novel, nuclear functions of eIF4E and how they
      contribute to eIF4E's growth-activating and oncogenic properties. Both the
      cytoplasmic and nuclear functions of eIF4E appear to be dependent on its
      intrinsic ability to bind to the 5' m7G cap of mRNA. For example, Promyelocytic
      Leukemia Protein (PML) potentially acts as a negative regulator of nuclear eIF4E
      function by decreasing eIF4E's affinity for the m7G cap. Therefore, eIF4E protein
      is flexible enough to utilize a common biochemical activity, such as m7G cap
      binding, to participate in divergent processes in different cellular
      compartments.

PMID- 11963653
TI  - A gene encoding a novel anti-adhesive protein is expressed in growing cells and
      restricted to anterior-like cells during development of Dictyostelium.
AB  - The Dictyostelium gene ampA, initially identified by the D11 cDNA, encodes a
      novel anti-adhesive-like protein. The ampA gene product inhibits premature cell
      agglutination during growth and modulates cell-cell and cell-substrate adhesion
      during development. Analysis of the promoter indicates that cap site-proximal
      sequence directs ampA expression during both growth and early development.
      Expression following tip formation is controlled by more distal sequence, which
      contains TTGA repeats known to regulate prestalk cell gene expression in other
      promoters. Comparison of reporter gene expression and endogenous mRNA
      accumulation indicates that during growth the ampA gene is expressed in an
      increasing number of cells as a function of density. The number of cells
      expressing the ampA gene drops as development initiates, but the cells that
      continue to express the gene do so at high levels. These cells are initially
      scattered throughout the entire aggregate. By the tip formation stage, however,
      the majority of ampA-expressing cells are localized to the mound periphery, with
      only a few cells remaining scattered in the upper portion of the mound. In the
      final culminant, ampA is expressed only in the upper cup, lower cup, and basal
      disc. Although reporter expression is observed in cells that migrate anteriorly
      to a banded region just posterior to the tip, expression is rarely observed in
      the extreme tip. AmpA protein however, is localized to the tip as well as to ALCs
      during late development. The results presented here suggest that ampA gene
      expression is shut off in ALCs that continue along the prestalk differentiation
      pathway before they are added to the primordial stalk.

PMID- 11963654
TI  - Thyroid hormones are important for embryonic to larval transitory phase in
      zebrafish.
AB  - In zebrafish, like many other teleost species, the development and
      differentiation of many major organs continue unabated into the yolk-sac larval
      stage before culminating in a free-swimming larva capable of exogenous feeding.
      We investigated the role of thyroid hormone (TH) in this important embryonic to
      larval transitory phase. Thyroid hormone receptor (TR) alpha and beta mRNAs are
      expressed during the early stages of zebrafish embryonic development. Beginning
      from the midblastula stage, the level of TR beta mRNAs increases dramatically and
      is maintained until the end of the transitory phase. Excessive exogenous
      thyroxine (T4; 30 nM) is toxic and causes severe developmental defects.
      Cotreatment of embryos with amiodarone, an antagonist of TR, and goitrogen
      methimazole (MMI) lead to severe retardation in the maturation of the
      gastrointestinal system, swim bladder, and the lower jaw cartilages and the
      resorption of the yolk sac. The developmental arrest is lethal, and treated
      larvae do not survive beyond 7 day postfertilization (dpf), but can be completely
      rescued by the presence of 10 nM T4. We propose that the embryonic to larval
      transitory phase in many teleost species is characterized by its dependency on
      the timely synthesis of TH and the concomitant autoinductive increase in TR beta
      mRNA levels.

PMID- 11963655
TI  - EphA4 catalytic activity causes inhibition of RhoA GTPase in Xenopus laevis
      embryos.
AB  - The Eph family of receptor tyrosine kinases is involved in limiting cell and
      tissue interactions via a repulsive mechanism. The mechanism of repulsion
      involves reorganizing the actin cytoskeleton, but little is known of the
      molecular components that connect the receptor to the actin cytoskeleton. Recent
      studies in retinal ganglion cells have demonstrated that EphA4 activates the
      small GTPase Rho. We have investigated the involvement of Rho in signaling
      downstream from EphA4. As a model system, we have used a chimeric receptor called
      EPP that we express and activate in early Xenopus embryos. Previous studies
      demonstrated that EPP activation leads to loss of cell-cell adhesion and change
      in cell shape, plus loss of aspects of cell polarity in epithelial cells, such as
      apical microvilli and the apical/basolateral boundary. In this study, we show
      that injecting inhibitors of Rho GTPases into early Xenopus embryos produces a
      phenotype very similar to that resulting from EPP activation. More importantly,
      expression of a constitutively active form of Xenopus RhoA (XRhoA) concurrent
      with activated EPP rescued embryos from the loss of cell-cell adhesion and change
      in cell shape associated with EPP. These data argue that, in contrast to the case
      in retinal ganglion cells, EphA4 in early Xenopus embryos acts to inhibit RhoA,
      suggesting that this receptor may regulate Rho differently (and therefore affect
      the cytoskeleton differently) in neuronal and non-neuronal cells. Furthermore,
      overexpression of ephexin, a novel guanine nucleotide exchange factor for Rho
      family GTPases, also blocks EPP-induced dissociation. This suggests that EphA4,
      which has been demonstrated to activate ephexin in cultured neuronal cells, may
      also target Rho GTPase via an ephexin-independent pathway.

PMID- 11963656
TI  - Ectopic expression of desmin in the epidermis of transgenic mice permits
      development of a normal epidermis.
AB  - Cell architecture is largely based on the interaction of cytoskeletal proteins,
      which include intermediate filaments (IF), microfilaments, microtubules, as well
      as their type-specific membrane-attachment structures and associated proteins. In
      order to further our understanding of IF proteins and to address the fundamental
      issue whether different IF perform unique functions in different tissues, we
      expressed a desmin transgene in the basal epidermis of mice. Ectopic expression
      of desmin led to the formation of an additional, keratin-independent IF
      cytoskeleton and did not interfere with the keratin-desmosome interaction. We
      show that ectopic expression of a type III IF protein in basal keratinocytes did
      not interfere with the normal epidermal architecture and the program of terminal
      differentiation. This demonstrated that keratinocytes suffered no obvious
      detrimental effects from extra desmin filaments in their cytoplasm. In addition,
      we asked whether stable expression of desmin could rescue K5 null mice, which
      served as a model for severe EBS. Transgenic mice ectopically expressing desmin
      in the basal layer were mated with K5 heterozygous deficient animals to generate
      desmin rescue mice and analysed. In summary, our study support the notion that
      the different IF like desmin or keratins composing a IF network in vivo are
      central to cytoskeletal architecture and design in cells.

PMID- 11963657
TI  - Animal productivity and animal welfare.

PMID- 11963658
TI  - An ethicist's commentary on guarding against conflict of interest.

PMID- 11963659
TI  - Foreign animal diseases and Canadian wildlife: reasons for concern and the
      elements of preparedness.

PMID- 11963660
TI  - National serologic survey for trichinellosis in sows in Canada 1996-1997.
AB  - Sera from 14,408 market sows from the Canadian domestic swine herd were tested
      for trichinellosis using an indirect-ELISA as a screening test and a competitive
      ELISA for confirmatory testing. Three sera (0.02%) gave low level reactions on
      the competitive ELISA. These reactions were considered nonspecific, and this
      designation was supported by data from previous and subsequent national surveys,
      in which serologic, trichinoscopic, and digestion test methodologies was used.
      This study provides additional evidence that Canada is free of trichinellosis in
      domestic swine.

PMID- 11963662
TI  - Pyogranulomatous panniculitis in a cat associated with infection by the
      Mycobacterium fortuitum/peregrinum group.
AB  - A 6-year-old, spayed female, American domestic shorthair was presented with a 10
      month history of nodules on the dorsum. Diagnosis of pyogranulomatous
      panniculitis caused by Mycobacterium fortuitum/peregrinum group was achieved by
      using tissue culture, chromatography, and histopathologic examination.
      Pathological findings, diagnosis, and clinical management of the condition are
      discussed.

PMID- 11963661
TI  - Factors affecting breeding soundness classification of beef bulls examined at the
      Western College of Veterinary Medicine.
AB  - Breeding soundness evaluation records from 2110 beef bulls, for the period of
      1986 to 1999, were analyzed to determine the prevalence and importance of factors
      affecting breeding soundness classification. The percentage of all bulls
      classified as satisfactory ranged from 49.0% in January to 73.3% in May. The
      percentage of physically normal bulls with satisfactory semen quality ranged from
      65.7% in January to 87.5% in June. Poor body condition or excessive body
      condition, below average or below the recommended minimum scrotal circumference,
      lameness, and severe scrotal frostbite significantly reduced the probability of a
      satisfactory breeding soundness classification. The percentage of sperm with
      midpiece defects declined significantly and the percentage of sperm with head
      defects increased significantly with the approach of summer. Photoperiod, cold
      stress, poor or excessive body condition, and reduced feed quality may interact
      to reduce semen quality in the winter months.

PMID- 11963663
TI  - Iatrogenic proximal urethral obstruction after inadvertent prostatectomy during
      bilateral perineal herniorrhaphy in a dog.
AB  - Proximal urethral obstruction was diagnosed 2 days after bilateral perineal
      herniorrhaphy in a 12-year-old male Pomeranian-cross dog. The obstruction was
      caused by ligation of the proximal urethra during resection of a presumed
      paraprostatic cyst. Surgical repair involved reconstruction of the urethra and
      bladder wall, but urinary incontinence persisted.

PMID- 11963664
TI  - Ethylene glycol toxicosis in a free-ranging raccoon (Procyon lotor) from Prince
      Edward Island.
AB  - A juvenile free-ranging raccoon (Procyon lotor) was presented for acute onset of
      abnormal mentation and seizures. Ethylene glycol toxicosis was diagnosed on
      postmortem examination. This report highlights the importance of including
      ethylene glycol toxicosis on the list of differential diagnoses for abnormal
      mentation and seizures in free-ranging raccoons.

PMID- 11963665
TI  - Exertional rhabdomyolysis in a 4-year-old standardbred filly.
AB  - A young standardbred filly became stiff and uncomfortable after racing. A day
      later, creatine kinase, aspartate aminotransferase, and lactic dehydrogenase
      levels were markedly elevated. Exertional rhabdomyolysis was diagnosed. Limited
      exercise and a low carbohydrate, high fat diet were prescribed. Eight days later,
      the filly was raced again without consequences.

PMID- 11963666
TI  - Melanocytic glaucoma in a cairn terrier.
AB  - Melanocytic glaucoma, previously known as pigmentary glaucoma, is characterized
      by diffuse intraocular infiltration of heavily pigmented melanocytes. This
      unusual ocular disorder has been documented only in the cairn terrier and is
      considered familial. Treatment strategies are based on evidence that the
      condition is slowly progressive but not neoplastic.

PMID- 11963667
TI  - Biologic repair of fractures.

PMID- 11963668
TI  - The art of retailing in veterinary practice.

PMID- 11963670
TI  - Disaster management requires planning, improvising, and evaluating.

PMID- 11963669
TI  - Diagnostic ophthalmology.

PMID- 11963671
TI  - Bernese periacetabular osteotomy for hip dysplasia in young adults.
AB  - Hip dysplasia is one of the most common disorders of the hip, presenting in the
      first three years of life. Literature has shown that an association exists
      between developmental dysplasia of the hip and the development of secondary hip
      osteoarthritis in early adulthood. Treatment options are directed toward
      relieving symptoms and delaying or preventing the onset of arthritis in the
      affected hip. Total hip arthroplasty is a surgical option, but has been
      associated with a high rate of failure in younger, physically active patients.
      This article discusses the Bernese periacetabular osteotomy procedure as a
      treatment modality, which restores coverage of the femoral head with the
      acetabulum. Changing the anatomy allows the surgeon to increase the surface area
      of the femoral head that bears the patient's weight. Increasing the weight
      bearing surface may prevent further damage to the hip's cartilage and delay the
      onset of osteoarthritis.

PMID- 11963672
TI  - Laparoscopic radical prostatectomy.
AB  - Prostate cancer is the second leading cause of cancer deaths among men, after
      lung cancer. Traditionally, the traumatic open radical prostatectomy procedure
      was the only treatment option available. Although nerve-sparing techniques have
      evolved, the development of laparoscopic radical prostatectomy (LRP) has been one
      of the most significant changes in surgical treatment of the disease. Like many
      minimally invasive abdominal procedures, LRP reduces trauma, resulting in less
      postoperative pain, reduced length of hospital stay, and more rapid return to
      normal activity when compared to open radical prostatectomy. This article
      describes the preoperative, intraoperative, and postoperative care of a patient
      undergoing LRP. It is anticipated that LRP will be the future standard for
      treatment of prostate cancer that requires radical surgery.

PMID- 11963673
TI  - Responding to a fire at a pediatric hospital.
AB  - Disaster preparedness in health care organizations facilitates a formalized
      response to major incidents or disasters. This article reviews a man-made
      disaster, a fire at a large pediatric hospital. How the fire started, patient
      evacuation, redirecting services, timing of events, key players, geographic
      factors, communications, and recovery and restoration of care are discussed.
      Lessons learned and Information on disaster preparedness also are presented.

PMID- 11963674
TI  - Perioperative patient education for retinal surgery.
AB  - Anticipation of retinal surgery and fear of permanent vision loss can be
      stressful for patients. When patients first are diagnosed with retinal problems
      and informed that ocular surgery is required, they may not be psychologically or
      emotionally ready to absorb the information needed to prepare them for the
      postoperative recovery phase. Perioperative nurses have an opportunity to affect
      patient outcomes by providing information to patients before, during, and after
      surgery. Well-educated patients have the necessary knowledge to maximize
      compliance and afford themselves an optimal surgical outcome.

PMID- 11963675
TI  - Instructional bias--awareness and reduction in perioperative education.
AB  - Through the use of instructional materials, perioperative educators provide
      education to staff members, physicians, patients, and family members. Although
      accrediting bodies and scholars have addressed the importance of diversity in
      patient assessment and nursing care, there has been little discussion regarding
      how instructional materials incorporate cultural, age, and gender diversity. This
      article defines bias and explores six forms of instructional bias. Suggestions
      are offered on ways to reduce or eliminate bias in instructional materials.

PMID- 11963677
TI  - Successful performance improvement.

PMID- 11963676
TI  - Ethics in perioperative practice--principles and applications.
AB  - Though often difficult, ethical decision making is necessary when caring for
      surgical patients. Perioperative nurses have to recognize ethical dilemmas and be
      prepared to take action based on the ethical code outlined in the American Nurses
      Association's (ANA's) Code of Ethics for Nurses with Interpretive Statements. In
      this first of a nine-part series that will help perioperative nurses relate the
      ANA code to their own area of practice, the author looks at the first statement,
      which emphasizes respect for people.

PMID- 11963678
TI  - Filling the void created by reductions in nurse staffing.

PMID- 11963680
TI  - Are emotional distress claims recognized in a court of law?

PMID- 11963681
TI  - Recommended practices for managing the patient receiving local anesthesia.

PMID- 11963682
TI  - Reporting medical errors and adverse events.

PMID- 11963683
TI  - Developing an effective state grassroots network.

PMID- 11963684
TI  - Providers need to see progress on Medicare reform.

PMID- 11963685
TI  - Computer-mediated addiction services: tomorrow won't look like today.

PMID- 11963687
TI  - Prescribing the 'employment pill'.

PMID- 11963688
TI  - Merging the clinical with the fiscal.

PMID- 11963689
TI  - A clinician's perspective on providers' liability exposure.

PMID- 11963690
TI  - Behavioral/primary care integration: a failed venture.

PMID- 11963691
TI  - Addiction providers. Surviving isn't enough.

PMID- 11963692
TI  - By professionals, for professionals. Betty Ford program lets clients connect with
      peers.

PMID- 11963693
TI  - Starting off on the right foot. NAATP honors Ashley for improving admissions
      process.

PMID- 11963694
TI  - Fluids: a balancing act.

PMID- 11963695
TI  - Fluids, fibre and constipation.

PMID- 11963696
TI  - Intermittent catheterisation: draining the bladder.

PMID- 11963697
TI  - Quality of life with faecal continence problems.

PMID- 11963698
TI  - Treating inflammatory bowel disease.

PMID- 11963699
TI  - Continence products: the role of evaluation.

PMID- 11963700
TI  - Good practice guidance for continence services.

PMID- 11963701
TI  - User support groups in continence care.

PMID- 11963702
TI  - Helping patients to maintain a healthy fluid balance.

PMID- 11963703
TI  - Maintaining fluid balance in children.

PMID- 11963704
TI  - How age affects fluid intake.

PMID- 11963705
TI  - Managing excoriation.

PMID- 11963706
TI  - Recognising, managing and removing slough.

PMID- 11963707
TI  - When and how to use alginates.

PMID- 11963708
TI  - The sheepskin myth.

PMID- 11963709
TI  - Preventing and managing pressure ulcers on heels.

PMID- 11963710
TI  - Heel pressure ulcers: the extent of the problem.

PMID- 11963711
TI  - Sampling techniques.

PMID- 11963712
TI  - Assessing pigmented skin.

PMID- 11963713
TI  - Using emollients.

PMID- 11963714
TI  - Fraudulent practice.

PMID- 11963715
TI  - The psychological impact of skin disease.

PMID- 11963716
TI  - Skin reactions to toxic plants.

PMID- 11963717
TI  - [Current treatment strategies in breast carcinoma].

PMID- 11963718
TI  - [Breast carcinoma. Biological principles, classification and prognostic factors].

PMID- 11963719
TI  - [Adjuvant and neoadjuvant systemic therapy of breast carcinoma].

PMID- 11963720
TI  - [Chemotherapy and immunotherapy of metastasized breast carcinoma].

PMID- 11963721
TI  - [New therapeutic approaches: stem cell assisted high dose chemotherapy and
      molecular techniques in breast carcinoma].

PMID- 11963722
TI  - [Bacterial pneumonias].

PMID- 11963723
TI  - [Dyspnea, eosinophilia and pulmonary infiltration in a 19-year-old drug dependent
      patient].

PMID- 11963724
TI  - [Weight loss, arterial hypotension and severe hypoglycemia in a 29-year-old
      patient with type 1 diabetes mellitus].

PMID- 11963725
TI  - [Can decubitus ulcer always be prevented?].

PMID- 11963726
TI  - [Modern chemotherapy in bronchial carcinoma].

PMID- 11963727
TI  - [ACE inhibitors in high risk heart patients. Primary analysis of the HOPE study].

PMID- 11963728
TI  - [Technical aspects of MR coronary angiography].
AB  - Within the past several years, MR angiography (MRA) has experienced major
      technological improvements. Whereas the contrast enhanced MRA of non-coronary
      vessels has become established in routine clinical diagnostics, MR coronary
      angiography still represents technical challenges to the MR scientists and
      clinical investigators. To allow diagnostic quality MR coronary angiography,
      precise and reliable visualization of small tortuous vessels moving at fast speed
      is necessary. This article reviews the basic principles of MRA with special
      consideration to MR coronary artery imaging.

PMID- 11963729
TI  - [Stability of the Euro-score as an identification tool for patient risk groups --
      dependency of the applied documentation system].
AB  - From the different methods for risk adjustment, scores allow a rough
      classification of the patients. The Euroscore represents one of the most modern
      scores. The most recent version of the documentation system of the German Society
      for Thoracic and Cardiovascular Surgery may be used without extended extra-work
      to evaluate the Euroscore despite the presence of various limitations. The
      investigation of the scores with nearly complete adaptation of the variables of
      the quality assurance documentation to the original definition showed no
      substantial differences between the score groups. However, many methodological
      implications favor the development of self-evaluated models to obtain a most
      recent weight for each risk factor and to be able to take into account new
      therapeutical options. These models can be evaluated by the existing database and
      extended by the most recent data.

PMID- 11963731
TI  - [Long-term effects of rehabilitation of an outpatient "heart group". A case
      control study].
AB  - The effects of an outhospital cardiac rehabilitation program in "heart groups"
      (HG) are studied in a case-control design. The control group (KG) was collected
      by match-pairing from 12,560 cases of a rehabilitation clinic fitting in the
      relevant criteria to those of members of the HG. Patients of both groups (n =
      75/group) after myocardial infarction and CABG were followed up over 7.5 years.
      There was no significant difference in risk factor modification. Exercise
      tolerance improved significantly in the HG by increasing maximum work capacity by
      50% in spite of a mean age of 60 years at the beginning. Members of HG had
      significantly lesser cardiac complaints and lower need for cardiac medication.
      Cardiac morbidity was reduced by 54% and costs for medical care were lowered by
      47% in HG. Although effects of secondary prevention on reducing risk factors were
      still insufficient, exercise tolerance in higher age and quality of life were
      improved, reduction in medication and in the morbidity saved costs for the health
      system.

PMID- 11963730
TI  - [Use of heparin in acute myocardial infarction in routine clinical practice in
      Germany. Results of the MITRA and MIR registries].
AB  - OBJECTIVE: Among other adjunctive medication, heparin is widely used in the
      therapy of acute myocardial infarction (AMI) today. Large randomized trials,
      however, have shown inconclusive data on the benefit of adjunctive heparin
      therapy for patients with AMI. The aim of this study was to describe the use of
      heparin and complication rates in routine clinical practice today. METHODS: MITRA
      and MIR were multicenter registries of AMI patients in Germany. During the years
      1994 to 1998, 22,697 patients were registered with MITRA and MIR. Of these
      patients 49.9% received reperfusion therapy. RESULTS: 21,004 patients (92%)
      received heparin during acute therapy of AMI. The following factors were
      associated with withholding heparin: Bleeding at admission (OR 4.7; CI 3.2-6.8),
      cardiogenic shock (OR 1.8; CI 1.4-2.3) and fibrinolytic therapy with
      streptokinase (OR 2.1; CI 1.8-2.3). Complication rates of patients with heparin
      were only slightly higher than among those without heparin: 1.7% strokes and 1.9%
      bleedings were reported among the patients with fibrinolysis and heparin compared
      to 1.3% strokes and 1.4% bleedings among patients without heparin (p = ns).
      Mortality rates were 14.1% for patients with and 27.3% for patients without
      heparin (p < 0.001). CONCLUSIONS: Of the patients in MITRA and MIR 92% received
      heparin during AMI. Patients with active bleeding or in critical condition
      received heparin significantly less often. The selection of critically ill
      patients may have contributed to the high mortality of patients without heparin
      for AMI. Bleeding complication rates of patients with adjunctive heparin were
      only slightly higher than reported in randomized trials.

PMID- 11963732
TI  - Emotional attitudes toward symptoms and inadequate coping strategies are major
      determinants of patient delay in acute myocardial infarction.
AB  - BACKGROUND: Early reperfusion treatment in acute myocardial infarction (AMI)
      preserves ventricular function and saves lives. After onset of AMI symptoms,
      patients often delay for hours until the decision to seek medical help. AIM: Of
      the MI-heart (Myocardial Infarction--HElp seeking And ReacTions) study was to
      identify factors determining patient decision delay. METHODS: 739 consecutive
      patients with confirmed AMI (median age 65.3 years, 30.2% females) were studied
      after transfer from the intensive care unit. A standardized interview covered AMI
      symptoms, attitudes toward symptoms, coping strategies, and clinical and
      sociodemographic variables. RESULTS: Of patients, 93.3% knew an AMI could be
      deadly. 43.9% of the patients who suspected an AMI, and knew it could be deadly,
      decided late (> 1 hour) to seek medical help. In univariate analyses, attitudes
      toward symptoms and coping strategies had the highest impact on a late decision.
      Stepwise logistic regression identified the following independent contributors to
      a late decision to seek medical help (relative risk, 95% confidence interval):
      wanting to wait and see (3.53; 2.32-5.39), not taking symptoms seriously (2.47;
      1.64-3.72), not wanting to bother anybody (2.14; 1.29-3.57), symptoms improving
      at first (2.33; 1.52-3.56), asking others for advice (0.46; 0.30-0.71), taking
      pain medication (2.01; 1.01-4.03), age > 65 years (1.69; 1.17-2.44), very strong
      intensity of angina (0.60; 0.42-0.87). CONCLUSIONS: Emotional attitudes to AMI
      symptoms and inadequate coping strategies are the major determinants of patient
      decision delay. They should be considered as a key factor in patient and public
      education. Modification of these emotional factors might best be achieved by an
      individualized approach.

PMID- 11963733
TI  - [Are the acute effects of transdermal estradiol in postmenopausal women with
      coronary disease related to changes of the autonomic tone?].
AB  - The single application of estradiol in postmenopausal women with symptomatic
      coronary heart disease has an antiischemic effect, which seems to be mainly
      related to the relaxation of the vascular smooth muscle. Longterm replacement
      with estrogen in postmenopausal women reduces their increased sympathetic
      activity. The aim of the double-blinded study was to assess whether a single
      transdermal estradiol administration also has an effect on the sympathovagal
      balance and may additionally explain the acute effects of estradiol. Methods
      Fifteen women with symptomatic and angiographically proven coronary artery
      disease were cross-over randomized to two 100-microgram patches of estradiol or
      identical placebo. After one week the women received the opposite treatment. One
      day after patch application a 24-hour Holter-ECG recording was performed to
      assess the mean heart rate over 24 hours as well as time domain and frequency
      domain indices of the heart rate variability. Results The estradiol plasma
      concentration rose significantly from 354 +/- 176 pmol/l after placebo to 800 +/-
      260 pmol/l after estradiol application. Heart rate during placebo was 74 +/- 15
      bpm and during therapy 74 +/- 15 bpm. Heart rate variability was not different
      for time domain indices such as SDNN (estradiol: 64 +/- 31 ms; placebo: 65 +/- 33
      ms) or for frequency domain indices such as LF (estradiol: 15.8 +/- 8.0 ms;
      placebo: 15.3 +/- 9.4 ms) and HF (estradiol: 12.1 +/- 8.5 ms; placebo: 12.9 +/-
      9.9 ms). Conclusion A single transdermal application of estradiol did not modify
      heart rate or heart rate variability of women with coronary artery disease. The
      modulation of the autonomic tone does not seem to be a relevant mechanism of
      short-term estradiol effects.

PMID- 11963734
TI  - [Morphological and functional MRI studies after correction of aortic isthmus
      stenosis].
AB  - PURPOSE: To compare the results of different methods for postoperative assessment
      after coarctation repair by magnetic resonance imaging and to evaluate their
      reliability. The morphometric results are contrasted to functional parameters of
      CW Doppler, oscillometric pressure gradient and flow quantification in VEC-MRI.
      METHODS: 54 patients (age: 6 to 36 years) were assessed by MRI 3 to 31 years
      after coarctation repair. The aortic diameters were compared to growth-dependent
      normal values and to the diameter of the ascending (AA) and descending aorta
      (DA), and their mean values (MV). RESULTS: Patients after coarctation repair had
      mostly subnormal diameters of AA (mean value: 80% of normal) and AD (95% of
      normal). Compared to the control group, mean dispersion of AD diameters was
      significantly larger in the patient group (2.6 vs. 1.5 mm, p < 0.001). Degree of
      stenosis varied with the method. It was similar when using normal values and the
      diameter for DA, but dispersion was smaller when normal values were used.
      Correlation of the functional parameter to the degree of stenosis was weak. The
      highest correlation (r = 0.78) was reached when using normal values as the
      reference with mean cross-sectional velocity from VEC-MRI. CONCLUSION: The use of
      normal values as the reference for quantification of residual coarctation is more
      reliable than common methods. Since only one measurement is needed, it seems to
      be less susceptible to errors and more practical. MRI offers not only a tool for
      accurate morphologic assessment, but with VEC-MRI it is also possible to obtain a
      functional parameter which is superior to oscillometric pressure gradient and CW
      Doppler.

PMID- 11963735
TI  - [Transcatheter closure of atrial septal defects with the CardioSEAL occluder].
AB  - Data on mid- and long-term follow-up for the recent devices for closure of
      secundum-type atrial septal defects are limited. The purpose of our retrospective
      study was to report the effectiveness of transcatheter closure in patients with
      various morphological types of atrial septal defect other than centrally located
      defects within the oval fossa using the CardioSEAL and CardioSEAL-Starflex
      occluder. A total of 91 patients (age 1.5-71 years, median 6 years) underwent
      transcatheter closure. On the transesophageal echocardiogram, defect size varied
      from 6 to 18 mm with an estimated stretched diameter of 11 to 24 mm, median 15
      mm; the ratio of the stretched diameter to septal length ranged from 0.28 to
      0.68. Mean follow-up was 28.7 +/- 11,9 months (range 3-46 months). Isolated
      secundum-type defects were present in 59 patients (65%), multiple septal defects
      including patients with perforated atrial septal aneurysms and defects with
      deficient atrial rim in 32 patients (35%). Occlusion rate using device diameters
      from 23 to 40 mm increased from 66% (60/91 patients) immediately after
      implantation to 86% (48/56 patients) 24 months after implantation. Patients with
      isolated secundum-type defects presented with a significantly higher primary
      closure rate (45/59 patients, 76%) compared to patients with various defect
      morphology. Closure rate did not depend on the type of implanted device
      modification. No thrombus formation, sustained atrial arrhythmia or infective
      endocarditis occurred. Serial transthoracic echocardiographic findings revealed
      protrusion of one left-sided arm onto the right atrial aspect in 5 patients;
      malposition of one right-sided superior arm of the device was observed in 7
      patients. Fluoroscopy showed single fatigue fracture in 7 patients (7.7%) within
      the first 6 months after implantation. These results demonstrate that
      transcatheter closure with the double umbrella device was effective and safe on
      medium-term follow-up and could be extended to atrial septal defects of various
      morphology.

PMID- 11963736
TI  - [Suicide attempt with insulin as a cause of myocardial infarct].
AB  - We report the case of a 31 year old healthy man without coronary risk factors,
      who made a suicide attempt with insulin caused by a chronic schizoid psychosis.
      The man was admitted to the hospital 14 hours later with non-specific chest pain
      and dizziness as clinical signs of a lateral wall myocardial infarction. The
      coronary angiography demonstrated intact coronary circulation and a broad area of
      myocardial damage of the left ventricular lateral wall. It is hypothesized that
      coronary artery vasospasm induced by hypoglycemia/hyperinsulinemia caused the
      myocardial infarction.

PMID- 11963737
TI  - [Primary stenting of thrombotic occluded main coronary artery in cardiogenic
      shock].
AB  - Acute left main coronary artery (LMCA) occlusion is associated with a high
      mortality rate. The majority of patients with this clinical condition die
      suddenly or from cardiogenic shock. We report a case of cardiogenic shock
      resulting from acute main coronary occlusion. Emergency cardiac catheterization
      was performed and coronary angiography showed a totally occluded LMCA. Prompt
      revascularization by means of primary LMCA stenting was successful and the
      patient was discharged 16 days later without neurological deficit or clinical
      signs of heart failure. We suggest that the rapid coronary angiography followed
      by angioplasty and primary stent implantation was instrumental in saving this
      patient's life.

PMID- 11963739
TI  - ["Memory, speak..." Joy and frustration of jubilees].

PMID- 11963738
TI  - [Pericardial tamponade in rupture of a right coronary artery aneurysm].
AB  - Cardiovascular magnetic resonance is a valid and accurate tool for the assessment
      of structural and functional disorders of the heart. Through combination of
      morphologic and functional studies, it is possible to form a quick diagnosis with
      a noninvasive examination. In this case, MR-imaging shows a pericardial effusion
      and a 5 x 5 cm large, well-circumscribed hematoma with displacement of the right
      coronary artery, which was also visible with other examination techniques as an
      unclear intracardial mass. At operation a large aneurysm of the right coronary
      artery was exposed, in addition to a hemorrhagic pericardial effusion.

PMID- 11963740
TI  - [Hemostasis-related risk profile in venous thrombosis].

PMID- 11963742
TI  - [Postoperative erythropoietin for sparing allotransfusions].

PMID- 11963741
TI  - [Fever of unknown origin, head and muscle pain, hemoptysis, hepatosplenomegaly
      and icterus. 2 case reports].

PMID- 11963743
TI  - [Drug therapy of unstable angina pectoris].

PMID- 11963744
TI  - [Chronic venous insufficiency].

PMID- 11963745
TI  - [Diagnostic imaging of deep leg and pelvic vein thromboses].

PMID- 11963746
TI  - [Differential therapy of deep venous thrombosis of the leg veins].

PMID- 11963747
TI  - [Prevention of thrombosis in internal medicine].

PMID- 11963748
TI  - [Interrelations between lymphatic vessels and venous diseases].

PMID- 11963749
TI  - [Diagnosis and therapy of diseases of the lymph vessels].

PMID- 11963750
TI  - [Surgical prevention and therapy of chronic venous insufficiency].

PMID- 11963751
TI  - [Molecular genetic diagnosis in hematology and oncology].

PMID- 11963752
TI  - [Clubbed fingers and dysphagia in a 38-year-old patient].

PMID- 11963753
TI  - [Endocrine tumors. Often misdiagnosed and treated too late].

PMID- 11963754
TI  - [Molecular pathogenesis of endocrine tumors].

PMID- 11963755
TI  - [Diagnosis and therapy of differentiated thyroid gland carcinomas].

PMID- 11963756
TI  - [Malignant tumors of the adrenal cortex].

PMID- 11963757
TI  - [Benign and malignant pheochromocytoma].

PMID- 11963759
TI  - [Therapy of endocrine gastrointestinal tumors].

PMID- 11963758
TI  - [Neuroendocrine tumors of the gastrointestinal-pancreatic system. Classification
      and diagnosis].

PMID- 11963760
TI  - [Proctology].

PMID- 11963761
TI  - [57-year-old patient with collapse during automobile driving].

PMID- 11963762
TI  - [Pancreatic duct stenosis of uncertain origin. A case of diagnostic dilemma].

PMID- 11963763
TI  - [Pneumothorax caused by a ruptured emphysema bulla].

PMID- 11963764
TI  - [Current pharmacotherapy of chronic myeloid leukemia].

PMID- 11963765
TI  - [Severe heart failure--effects of carvedilol therapy. The Copernicus Study].

PMID- 11963766
TI  - [Alcohol-associated organ damage. Health sequelae caused by moderate alcohol
      drinking].

PMID- 11963767
TI  - [Therapy of liver diseases. Report on the 8th Postgraduate Course of the German
      Society of Digestive and Metabolic Diseases, 12 September 2001 in Munster].

PMID- 11963768
TI  - [Duplex ultrasound imaging of arteries and veins].

PMID- 11963769
TI  - [The Frankfurt concept for health counseling for men].
AB  - The discussion on the difference between the sexes received significant impulses
      from the formation of feminist theory. Masculinity was interpreted in a rather
      morally negative manner. Masculinity continuously endeavors to achieve
      reproduction and self-confirmation. Competitive pursuit of hegemony is the
      preeminent pattern by which masculine identity is formed. Male socialization
      leads to externalization, which impedes the development of communicative skills.
      Males tend to lead a high-risk life-style, which instrumentalizes their body.
      Symptoms are less often interpreted as warning signals, reflected in a
      significantly reduced life expectancy in comparison to females. In view of the
      specific male socialization, the Frankfurt concept of "men's health counseling"
      attempts to create a professional atmosphere in which men seeking advice are
      offered the opportunity to consult a specialist on all topics of men's health
      anonymously and, for the moment, free of charge.

PMID- 11963770
TI  - [LaMedica. The medical education academy on the internet].
AB  - At present, "modern media" are still a novelty in medical education. The
      "LaMedica Project"--a program supported by the Federal Ministry for Education and
      Research--intends to provide an Internet-based education and training system for
      the entire field of medicine, using all available media resources. This online
      educational program will provide subjects for medical laypersons as well as
      medical experts. Various styles of learning and different learning requests will
      be promoted. The project presented mirrors the cutting edge of database
      technology, computer-based training and media didactics, critical content
      processing as well as supplying individual subjects. This report summarizes our
      10 months of experience with this program at the Department for Urology and
      Pediatric Urology of the Johann Wolfgang Goethe University of Frankfurt Main.

PMID- 11963771
TI  - [Human papillomaviruses (HPV) in urology. I: 10 years results of
      interdisciplinary HPV diagnosis].
AB  - Human papillomaviruses play a pre-eminent role as the most frequent sexually
      transmitted virus in urology. However, a pathogenetic connection between these
      viruses and urological cancers has not been proved so far, in contrast to the
      correlation with cervical cancer. Our 10-year experience with urological partner
      diagnostics and therapy surveillance in 788 patients form the empirical basis for
      the detection of clinical and subclinical HPV efflorescences, rates of partner
      infection and the benefit of laboratory techniques for HPV detection. Commercial
      HPV test methods only detect a fraction of the HPV types affecting the external
      genitals and the urethra that are demonstrated in a reference laboratory. HPV
      analyses are not appropriate for routine diagnostics, but should be used solely
      in research projects.

PMID- 11963772
TI  - [Human papillomaviruses (HPV) in urology. II: 10 years evaluation of differential
      HPV therapy].
AB  - Human papillomaviruses can give rise to histoclinical changes in the epithelium
      of the anogenital region. These have to be considered and treated differentially
      on the basis of their morphology, size, number, location and oncogenic relevance.
      Up until now, no method of treatment has proved to be clearly superior to others
      or to be especially suitable for the comprehensive therapy of all varieties of
      HPV efflorescences. We will present and evaluate a comprehensive concept of HPV
      treatment that takes into consideration the medical aspects of HPV associated
      lesions, the treatment choice of the patient, drugs approval and the legal
      responsibility for the individual methods of HPV treatment. Our experience
      enables us to critically analyze the current HPV therapy guidelines of various
      specialist societies which do not adequately take specific urological aspects
      into consideration.

PMID- 11963773
TI  - [Familial prostate carcinoma in Germany].
AB  - Epidemiologic studies have shown that hereditary forms account for approximately
      10% of all prostate cancers. The identification of several susceptibility loci
      harboring predisposing genes indicates the genetic heterogeneity of prostate
      cancer. The conflicting results of different linkage analyses may be explained by
      a varying contribution of each locus within different family collections and
      reflect differences of allele frequencies across different populations. In the
      present study we recorded the incidence of familial prostate cancer in Germany
      and performed descriptive analysis of the epidemiological data. In spite of a
      significant ascertainment bias, only 19% of all prostate cancers were familial.
      In 94% of families there were three affected relatives at most. Large prostate
      cancer families with at least five affected persons were rare (2%). Descriptive
      analysis revealed that only 42% of all pedigrees followed an autosomal-dominant
      pattern of transmission; the other pedigrees showed an X-chromosomal or recessive
      mode of inheritance. These data confirm the genetic heterogeneity of hereditary
      prostate cancer and imply that previously published epidemiological data cannot
      be transferred to the German population.

PMID- 11963774
TI  - [Chronic sacral bilateral neuromodulation. Using a minimal invasive implantation
      technique in patients with disorders of bladder function].
AB  - The implantable neuromodulation system described by Tanagho and Schmidt enables
      unilateral sacral nerve stimulation. Reports have been made on sacral
      neuromodulation failures of up to 50% in patients undergoing this procedure. We
      chose the bilateral electrode implantation and a minimal invasive laminectomy to
      ensure a more effective modulation and better placement and fixation of the
      electrodes. After successful assessment using a peripheral nerve evaluation test,
      20 patients (14 with detrusor instability, 6 with hypocontractile detrusor)
      underwent minimally invasive laminectomy and bilateral electrode placement. In
      the patients with detrusor instability, the incontinence episodes were reduced
      from 7.2 to 1 per day and the bladder capacity improved from 198 to 352 ml. In
      patients with hypocontractile detrusor, the initial residual urine level of 450
      ml dropped to 108 ml. Maximum detrusor pressure during micturition rose from 12
      cmH2O initially to 34 cmH2O. The average follow up period was 17.5 months. There
      was no sign of deterioration in the modulation effect in any of the patients.
      Bilateral electrode implantation and the new sacral approach allow optimal
      neuromodulation in patients with bladder dysfunction. Laminectomy enables optimum
      electrode placement and fixation with minimal trauma.

PMID- 11963775
TI  - [Radical prostatectomy in clinically localized prostate carcinoma. Pro
      laparoscopic approach].
AB  - Systematic development of laparoscopy during the last decade has led to
      establishing laparoscopic radical prostatectomy (LRP) as a surgical procedure. On
      the basis of extensive experience at our center, the advantages of the minimally
      invasive method are described as well as the problems still in existence. Reduced
      trauma caused by laparoscopic access in combination with clearly reduced blood
      loss has resulted in less morbidity after laparoscopic procedures. This is
      reflected in a shorter postoperative stay in hospital and faster convalescence.
      LRP as an ambitious and complex procedure has an average complication rate of
      12%, which shows that the method has surpassed the stage of experimental surgery.
      By direct comparison, the costs of LRP are higher than for the open surgical
      procedure, but on the whole this is economically balanced by the lower morbidity,
      shorter hospital stay, and faster convalescence. The progress in technology to be
      expected in the field of laparoscopy will further increase quality, precision,
      and safety of LRP and thus contribute to the establishment of laparoscopic
      radical prostatectomy as a surgical method of choice.

PMID- 11963776
TI  - [How will urology cope with the new health care system?].
AB  - According to the report 2000 issued by the expert advisory committee on the
      health care system, improvement in performance requires, among other things,
      awareness of the need for more economic efficiency, better quality of medical
      care, and definition of targets. Disease prevention and early diagnosis are the
      main objectives of health policy and practice. Data mining becomes an important
      tool in epidemiological and clinical research. Urologists are called upon to
      engage in clinical studies to establish therapeutic standards and guidelines.
      Results of research must be put in to practice faster. Doctors ought to respond
      to changes in patients' attitudes.

PMID- 11963777
TI  - [Radical prostatectomy in clinically localized prostate carcinoma. Contra
      laparoscopic approach].
AB  - Laparoscopic radical prostatectomy (LRP) offers an alternative to open
      prostatectomy in the treatment of clinically localized prostate cancer. However,
      when considering this new approach, oncological and functional results must be
      comparable to those of open retropublic prostatectomy (RRP). Long-term follow-up
      data for LRP are still lacking. RRP shows biochemical-free survival rates of 80%
      after 5 and 10 years. When evaluating functional results, data for postoperative
      erectile function after LRP are unclear. The functional data of postoperative
      continence after LRP seemed to be comparable to those of RRP. Even when
      considering aspects of morbidity and economy, RRP remains the golden standard in
      the treatment of clinically localized prostate cancer. Oncological and functional
      results are still preliminary for LRP.

PMID- 11963779
TI  - [Quality assurance in case total and special reimbursement. A topic for the
      urologist].

PMID- 11963778
TI  - [Spermatocytic seminoma. Report of 2 personal cases and review of the
      literature].
AB  - The spermatocytic seminoma is a distinct testicular neoplasm with a low tendency
      to metastasize. Two own cases with the diagnosis of a spermatocytic seminoma are
      presented. A third patient is described, where the initial diagnosis of a
      spermatocytic seminoma was retrospectively changed to classical seminoma after
      developing retroperitoneal relapse during surveillance. A literature review
      revealed distinct histopathological characteristics and a remarkably good
      prognosis for spermatocytic seminoma. With only one case of relapse confirmed in
      the literature, in these patients postoperative treatment can safely be omitted
      in favor of surveillance. In case of spermatocytic seminoma diagnosis should be
      confirmed by a second pathologist.

PMID- 11963780
TI  - [Varicocele testis in childhood and adolescence].

PMID- 11963781
TI  - ["Biological", but fatal. Letters as potential biological weapons].

PMID- 11963782
TI  - [Inhibition of cellular signal transduction cascades. A future anti-invasive
      therapeutic strategy for cancers of the head and neck region].
AB  - BACKGROUND: Squamous cell carcinomas of the head and neck are considered to be
      highly aggressive cancers. The 5-year survival rate of patients with this disease
      depends on whether a locoregional relapse occurs and if so, how early after the
      initial treatment. Disease was found to relapse more frequently in patients
      suffering from cancers with an invasive growth pattern. It was therefore
      concluded that cancer cell invasion influences the patient's survival. While
      considerable efforts are made to develop treatment regimens for relapsing
      disease, a novel approach consists of the prevention of the disease recurrence
      through the inhibition of cancer cell invasion. METHOD: Literature search.
      RESULTS: We summarize in this article the mechanisms of tumor invasion, focusing
      on the regulation of tumor proteases, which are essential for cancer invasion,
      and provide an overview of preliminary results with novel anti-invasive treatment
      strategies. CONCLUSION: Novel anti-invasive treatment regimens based on an
      understanding of molecular cancer invasion mechanisms may be used in the future
      to treat patients with head and neck cancers.

PMID- 11963784
TI  - [Intraoral protrusion devices in obstructive sleep apnea. Dental findings and
      possible treatments].
AB  - BACKGROUND: Oral protrusive devices are regarded as an alternative treatment
      option for snoring and mild to moderate obstructive breathing disorders. In
      addition to the polysomnographic indication based on the respiratory and
      somnographic findings, healthy stomatognatic conditions with sufficient dental
      retention for the device are essential for a successful treatment. PATIENTS AND
      METHODS: The sleep laboratory of the University Hospital of Freiburg i. Br.
      referred 112 patients with obstructive sleep apnea to the Department of
      Orthodontics for treatment with an oral protrusive device. All patients were
      examined clinically and with a panoramic radiograph with regard to continuous
      treatment. RESULTS: To maximize treatment success and minimize dental side
      effects, close collaboration with dental colleagues is necessary in treatment
      with an oral protrusive device. CONCLUSIONS: Acute periodontitis, periodontal
      lesions, insufficient dental anchorage, and temporomandibular symptoms can result
      in unwanted dental side effects and therefore limit the indication of this
      therapeutic approach.

PMID- 11963783
TI  - [Orbital floor reconstruction. Comparison of a new perforated 0.15 mm thick PDS
      layer with established titanium dynamic mesh].
AB  - INTRODUCTION: For surgical reconstruction of the orbital floor after blow-out
      fractures, a new perforated PDS (poly-p-dioxanon) foil (0.15 mm thickness) has
      recently become available. The main target of this prospective and randomized
      interdisciplinary clinical study was to compare this new PDS foil with the proven
      titanium dynamic mesh (0.3 mm thickness). PATIENTS/METHODS: Aside from the common
      diagnostic procedures, an extensive ophthalmologic examination was performed and
      documented preoperatively (U1), 4 days (U3), 1 month (U4), and 6 months (U5)
      postoperatively. RESULTS: In both groups the surgical procedure was tolerated
      well. The new perforated PDS foil turned out to be easier to handle
      intraoperatively because of smooth and clean cutting edges. The surgical
      treatment was well tolerated in all randomized groups. In contrast to the control
      group, the PDS and TD groups showed postoperatively a slight increase of the
      preoperative exophthalmos (mean 0.5 mm). CONCLUSION: The new perforated PDS foil
      is comparable concerning cosmetic and functional aspects. Especially with regard
      to stability after blow-out fractures, the new perforated PDS foil is equal to
      titanium dynamic mesh up to 20 mm in diameter. PDS foil is felt to be superior
      regarding bioresorption and due to the more convenient handling.

PMID- 11963785
TI  - [Prognostic factors in head-neck carcinomas].
AB  - Squamous cell carcinoma of the head and neck is one of the most common human
      cancers with an unchanged high rate of mortality despite improved diagnostic and
      therapeutic methods of the past twenty years. Latest advances of molecular
      biological methods contributed to the understanding of the multistep process of
      carcinogenesis. Genetic instability, dysregulation of cell cycle and apoptosis as
      well as changes of oncogenes and tumor suppressor genes are involved in
      carcinogenesis. So far, molecular markers do not fulfill the desired requirement
      of clinical relevance concerning early detection of cancer, estimation of
      prognosis and individualized therapy regimens in potential risk patients. With
      the establishment of the UICC TNM staging system first prognostic statements were
      made possible, which showed a positive correlation between tumor stage and
      prognosis. There is, however, a need of clinical and/or molecular parameters that
      reliably predict individual prognosis and results of individualized therapy. We
      discuss parameters that have been associated with prognosis of head and neck
      squamous cell carcinoma so far.

PMID- 11963786
TI  - [Collagenase 3 mRNA expression in squamous epithelial carcinomas of the
      oropharynx].
AB  - BACKGROUND: Metalloproteinases (MMP) are endopeptidases, which are able to
      degrade extracellular matrix. It is assumed that MMP play an important role in
      invasion and metastasis of malignomas. The expression of collagenase-3, also
      named MMP-13, was already detected in squamous cell carcinoma of the head and
      neck, but the significance in the process of metastasis is still unclear.
      PATIENTS AND METHODS: 36 tumor biopsies of oropharyngeal squamous cell carcinoma
      (10 cases N0, 26 patients N+) and 12 biopsies of normal oropharyngeal mucosa were
      analysed with reverse transcriptase-PCR and Northern Blot for their mRNA
      expression of MMP-13 and TIMP-1, the physiological inhibitor of MMP-13. RESULTS:
      In 30 of 36 (83.3%) tumor biopsies a MMP-13-mRNA-expression was detected. In 9 of
      10 (90%) cases with N0-status and 21 of 26 (80.7%) cases with N(+)-neck the mRNA
      expression could be shown. There was no correlation between MMP-13-mRNA
      expression and N-status. In 34 tumor biopsies (94.4%) a TIMP-1-expression was
      detected. MMP-13-mRNA was not detected in normal oropharyngeal mucosa.
      CONCLUSIONS: It seems that MMP-13-mRNA-expression is not a prognostic factor for
      metastatic behavior of oropharyngeal cancer and therefore not helpful for further
      decisions on the therapy.

PMID- 11963787
TI  - [Vocabulary of young children with sensorineural deafness].
AB  - The primary aim of the study was to measure the receptive and expressive
      vocabulary with respect to clinical parameters and selected socio-demographic
      variables and to assess whether the size of vocabulary could be predicted by
      certain variables in a consecutive series of children identified as having
      bilateral sensorineural hearing loss ("Gottinger Hor-Sprachregister"). METHOD:
      All children aged between 2;6 to 6;3 years diagnosed in the Department of
      Phoniatrics/Pedaudiology of the University Gottingen as having a permanent
      bilateral sensorineural hearing impairment ("Gottinger Hor-Sprachregister") in a
      defined period (july 1995-september 2000) were examined with standardized
      receptive and expressive vocabulary tests as well as a nonverbal intelligence
      test (on average 5.5 months after diagnosis and 2.9 months after fitting with
      hearing aids). SAMPLE: 37 children (20 boys, 17 girls). Mean age at diagnosis:
      48.5 (SD 15.9; min. 18, max. 75) months, mean age at hearing aid fitting: 51
      months (SD 15.2). Multiple handicapped children, children with additional
      conductive hearing impairment and those with postnatal losses were excluded. The
      sample as a whole demonstrated lexical deficits of varying severity that were
      greater in the expressive than in the receptive vocabulary, depending on the
      clinical parameter. Children with congenital hearing impairment, with severe-to
      profound hearing impairment (> 70 dB) and bilingual children demonstrated on
      average the smallest receptive and expressive vocabulary. An early fitting with
      hearing aids did not correspond with a better lexical development when a severe
      to-profound hearing impairment existed. Severity of a hearing impairment and
      nonverbal intelligence significantly predicted the average size of the receptive
      vocabulary. A moderate hearing impairment, high non-verbal intelligence, and
      gender (female) emerged as the strongest significant predictors of the expressive
      vocabulary. The vocabulary test result of a bilateral sensorineurally hearing
      impaired child may be an indicator for early cognitive training.

PMID- 11963788
TI  - [Plastic external ear reduction in bilateral macrotia].
AB  - We present the rare case of a bilateral reduction of macrotic ears by a helical
      advancement according to Davis. It is a quite simple and reliable technique, that
      permits to hide the scars in the relief of the pinna.

PMID- 11963789
TI  - [Acoustic neurinoma with preserved inner ear function. Interesting audiologic
      constellation of findings].
AB  - Neurofibromatosis (NF) is a syndrome with multiple neuromas. With the central
      form or NF2 very often bilateral acoustic neuromas are found. Tumours derive from
      Schwann cells of the eighth cranial nerve; symptoms are tinnitus, hearing loss
      and vertigo. Therapy is surgical, if possible with the protection of remaining
      hearing function. We report the case of a 28 year old female patient with
      neurofibromatosis type 2. After complete resection of the left AN and partial
      resection of the right AN the patient suffered from bilateral complete deafness,
      although almost normal DPOAE can be recorded on one side. Therefore we find the
      classical neural deafness with intact function of outer haircells (OHC).

PMID- 11963790
TI  - [Malignant tumors don't grown in empty space].

PMID- 11963791
TI  - [Progressive oropharyngeal dysphagia. Neurinoma of the larynx].

PMID- 11963792
TI  - [Laser tonsillotomy].

PMID- 11963793
TI  - [News in medical law for the period May 2001 to October 2001].

PMID- 11963794
TI  - [Patient satisfaction in the hospital. Results of a prospective study exemplified
      by an ENT department].

PMID- 11963795
TI  - [Revision tympanoplasty].

PMID- 11963796
TI  - Pharmacogenomics: a critical component of patient stratification during drug
      development.

PMID- 11963797
TI  - Chips to hits 2001: an array of parallel technologies converge. October 28
      November 1, 2001, San Diego, CA, USA.

PMID- 11963799
TI  - Nuclear matrix proteins as biomarkers for breast cancer.
AB  - Breast cancer remains a leading cause of cancer death in women despite widespread
      screening, in part because screening mammography has high rates of false-negative
      results and because many women decline to have routine mammograms. The
      development of sensitive and specific assays for breast tumor markers would
      improve detection and facilitate screening, diagnosis, therapeutic monitoring and
      surveillance for recurrence. Nuclear matrix proteins (NMPs) are promising
      candidates for tumor markers because they are involved in malignant
      transformation. Therefore, they may be useful for screening and early diagnosis
      of small tumors. Proteomic analysis was used to demonstrate that a 28.3 kD serum
      protein, designated NMP66, can distinguish malignant disease from benign
      conditions and normal controls. NMP66 is now being evaluated as a potential
      biomarker for early breast cancer detection in large-scale clinical trials.

PMID- 11963798
TI  - Lp-PLA2: an emerging biomarker of coronary heart disease.
AB  - Cardiovascular disease is the leading cause of death in most industrialized
      countries. However, the diagnosis and management of coronary heart disease is far
      from optimal. Lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as
      platelet-activating factor acetylhydrolase, is an enzyme that hydrolyses oxidized
      phospholipids and is primarily associated with low-density lipoprotein. Discussed
      in this review is the accumulating evidence supporting the view that Lp-PLA2 is a
      potential biomarker of coronary heart disease and plays and an important
      proinflammatory role in the progression of atherosclerosis. A new ELISA method
      for the quantitative measurement of Lp-PLA2 mass in human plasma developed by
      diaDexus, Inc. is presented. Furthermore, potential clinical applications of Lp
      PLA2 mass measurements are proposed.

PMID- 11963800
TI  - Application of fetal DNA in maternal plasma for noninvasive prenatal diagnosis.
AB  - Prenatal diagnosis of fetal genetic conditions is a standard part of modern
      obstetric care. Many of the current methods rely on invasive methods and are
      associated with an inherent risk of fetal loss. Consequently, there has been a
      long-term goal for development of noninvasive prenatal diagnostic methods. In
      1997, the presence of fetal DNA in maternal plasma was first discovered through
      the detection of Y-chromosome-specific sequences in the plasma of women conceived
      with male fetuses. This discovery has opened up new possibilities in the
      development of noninvasive prenatal diagnostic methods through a source of fetal
      genetic material that could be conveniently accessible simply through the
      collection of a maternal peripheral blood sample. To date, there have been
      numerous reported applications, including fetal RhD genotyping, prenatal
      diagnosis of sex-linked disorders, paternally inherited genetic diseases and some
      pregnancy-associated conditions, including preeclampsia. More recently, there
      have been significant new developments with expanding number of potential
      applications.

PMID- 11963802
TI  - Molecular testing for hereditary hemochromatosis.
AB  - Recent molecular genetic testing methods for hereditary hemochromatosis (HH) and
      single nucleotide polymorphisms are summarized. Comparisons of various sample
      preparation and detection instrumentation are made in terms of automation, cost,
      high-throughput and feasibility of implementation in a clinical laboratory.
      Examples are given for the analysis of the two mutations associated with
      hereditary hemochromatosis (HH) by high-performance liquid chromatography,
      capillary electrophoresis and mass spectrometry based on single nucleotide
      extension. The trends for developing better genetic testing are discussed.

PMID- 11963801
TI  - Detection of disseminated tumor cells: strategies and diagnostic implications.
AB  - Disseminated cells from primary solid tumors are considered to be the cause of
      metastases formation and relapse of disease. Consequently, their detection is of
      high importance for staging, prognosis and decisions about adjuvant therapy.
      Residual disease is conventionally detected by histological evaluation of biopsy
      specimens. Continuing efforts to increase the sensitivity to identify occult
      tumor cells in lymph node, bone marrow and blood have led to the development of
      various strategies. This review will discuss histological, immunological and
      molecular approaches to detect micrometastases from solid tumors.

PMID- 11963803
TI  - RCA reactions can take place under true topological constraints.

PMID- 11963804
TI  - Pyrosequencing and Mayo Clinic collaborate on diagnostic tests.

PMID- 11963805
TI  - Quest Diagnostics receives FDA clearance for new Bio-Intact PTH test kit.

PMID- 11963806
TI  - FDA clears new test for rapid identification of breast cancer risk factors.

PMID- 11963807
TI  - Third Wave, Daiichi to develop personalized cancer treatment.

PMID- 11963808
TI  - Biosite receives clearance for the Triage TOX Drug Screen.

PMID- 11963809
TI  - Genetic testing: the future of smoking cessation therapy?
AB  - In the UK, approximately one-third of the population currently smoke. It is
      estimated that up to 70% of these smokers want to stop smoking but smoking
      cessation rates currently only stand at 20-30%. In order to reduce the health
      burden associated with smoking in the short-term we need to increase cessation
      rates. This will stem from deeper understanding of the processes involved in
      nicotine addiction, targeted therapy and the development of new pharmacological
      cessation agents. This article is not intended to be an exhaustive examination of
      nicotine addiction but rather an overview of some of the genetic aspects and how
      we can go on to use this knowledge in order to develop a genetic test to aid
      smoking cessation.

PMID- 11963810
TI  - Traceability of genetically modified organisms.
AB  - EU regulations stipulate the labeling of food products containing genetically
      modified organisms (GMOs) unless the GMO content is due to adventitious and
      unintended 'contamination' and not exceeding the 1% level at ingredient basis. In
      addition, member states have to ensure full traceability at all stages of the
      placing on the market of GMOs. Both requirements ensure consumers 'right to
      know', facilitate enforcement of regulatory requirements and are of importance
      for environmental monitoring and postmarket surveillance. Besides administrative
      procedures, such as used in quality certification systems, the significance of
      adequate molecular methods becomes more and more apparent. During the last decade
      a considerable number of molecular methods have been developed and validated that
      enable the detection, identification and quantification of GMO impurities. Most
      of them rely on the PCR technology and can only detect one specific stretch of
      DNA. It can, however, be anticipated that in the near future the situation will
      become more complex. The number of GMO varieties, including 'stacked-gene'
      varieties, which will enter the European Market will increase and it is likely
      that these varieties will harbor more variable constructs. New tools will be
      necessary to keep up with these developments. One of the most promising
      techniques is microarray analysis. This technique enables the screening for a
      large number of different GMOs within a single experiment.

PMID- 11963811
TI  - Digene launches hybrid capture expressArray kit.

PMID- 11963812
TI  - Fujirebio Diagnostics to market microtiter format assays.

PMID- 11963813
TI  - Molecular beacons: colorful analysis of nucleic acids.
AB  - The completion of the Humane Genome Project has resulted in an exponential rise
      in the demand for molecular diagnostic assays. To meet this demand, several
      innovative technologies have become available for performing homogeneous genetic
      analyses. For this type of assay, special detector probes are necessary. In 1996,
      Tyagi and Kramer described fluorogenic hairpin-shaped detector probes, called
      'molecular beacons', which are extraordinarily specific. Since they characterize
      alleles by the generation of fluorescent signals, they are perfectly suited for
      homogeneous genetic analysis. Molecular beacons assays are simple, fast,
      inexpensive, sensitive, utilize a high-throughput format, enable the testing of
      many samples simultaneously and allow the detection of a series of different
      agents in the same assay tube. This review is designed to give the reader a
      greater understanding of the exciting applications of molecular beacons in DNA,
      RNA and protein studies.

PMID- 11963814
TI  - Second European Meeting on Molecular Diagnostics. 11-12 October, 2001,
      Scheveningen, The Netherlands.

PMID- 11963815
TI  - Constraints and research needs in forecasting and prevention of malaria epidemics
      in India.

PMID- 11963816
TI  - A study on clinical profile of falciparum malaria in a tertiary care hospital in
      south India.
AB  - Malaria continues to be a major problem in tropical countries. To study the
      clinical features and complications of malaria in a tertiary care hospital in
      south India, records of 183 patients were analysed. Among 86 patients with P.
      falciparum and mixed infection, 24 (28 per cent) had cerebral malaria and 32 (37
      per cent) had hyperbilirubinemia. Twenty-three out of 32 (72 per cent) patients
      with jaundice had direct hyperbilirubinemia and elevated liver enzymes suggesting
      hepatocellular damage. Mortality of the order of 10 per cent was seen only in P.
      falciparum malaria. High incidence of hepatic involvement and hepatorenal failure
      were the unusual features observed in the study.

PMID- 11963817
TI  - Epidemiological observations on malaria in some parts of Darrang District, Assam.
AB  - A study on malaria conducted in tribal villages of Darrang district, Assam during
      April 1994 to March 1995 revealed that the malaria incidence due to Plasmodium
      falciparum was considerably high. Slide positivity rate (SPR) ranged between 2.3
      to 45.67 per cent with transmission from May to October. P. falciparum was the
      dominant species (91.7 per cent) followed by P. vivax (7.25 per cent) and mixed
      infection (Pv + Pf = 1.05 per cent). Malaria cases were recorded throughout the
      year in all the age groups including infants, however, age groups between 0-1 and
      21-30 years were more affected. Among 17 anophelines collected, Anopheles vagus,
      An. jamesii, An. crawfordi and An. minimus were the most abundant species. Known
      vectors of malaria like An. annularis, An. culicifacies, An. minimus, An.
      philippinensis and An. varuna were detected. Perennial transmission of malaria
      was attributed to low socio-economic conditions, poor surveillance and inadequate
      intervention measures.

PMID- 11963818
TI  - An outbreak of Plasmodium falciparum malaria due to Anopheles minimus in central
      Assam, India.
AB  - Epidemiological investigations were conducted in Nellie subcentre, PHC Jhargaon,
      under Morigaon district (Assam). The results of fever cases revealed 68 per cent
      slide positivity rate (SPR) and 40 per cent slide falciparum rate (SfR). The Pf
      proportion was > 87 per cent and remaining cases were P. vivax infections. An.
      minimus was incriminated as a malaria vector during the study period. The
      sporozoite rate was 3.08 per cent. The indoor man mosquito contact was 35 per
      bait/night as against 23 in outdoors. Results of susceptibility test revealed
      that the vector was still susceptible to both DDT and malathion at discriminating
      dosages. The study revealed that inadequate surveillance and vector control
      measures were contributing factors for malaria outbreak. In view of this,
      insecticide treated nets may be introduced to provide cost-effective control of
      malaria.

PMID- 11963819
TI  - Childhood malaria and use of bednets in Kolkata.

PMID- 11963820
TI  - A simple method for dissecting the salivary glands of mosquitoes.

PMID- 11963821
TI  - A randomized controlled trial comparing artemether and quinine in the treatment
      of cerebral malaria in Bangladesh.
AB  - A randomized controlled trial on 51 patients receiving artemether and 54 patients
      receiving quinine was undertaken to compare the effectiveness of intramuscular
      artemether and parenteral quinine in the treatment of cerebral malaria in adults
      in Bangladesh. Case fatality, fever and parasite clearance times were not
      significantly different in the two treatment groups. Coma resolution time was
      significantly delayed in artemether recipients. Results of the study suggest that
      treatment with artemether is as effective as parenteral quinine in the treatment
      of cerebral malaria in adults.

PMID- 11963822
TI  - Anatomical markers of activity in neuroendocrine systems: are we all 'fos-ed
      out'?
AB  - It has now been nearly 15 years since the immediate early gene, c-fos, and its
      protein product, Fos, were introduced as tools for determining activity changes
      within neurones of the nervous system. In the ensuing years, this approach was
      applied to neuroendocrine study with success. With it have come advances in our
      understanding of which neuroendocrine neurones respond to various stimuli and how
      other central nervous system components interact with neuroendocrine neurones.
      Use of combined tract-tracing approaches, as well as double-labelling for Fos and
      transmitter markers, have added to characterization of neuroendocrine circuits.
      The delineation of the signal transduction cascades that induce Fos expression
      has led to establishment of the relationship between neurone firing and Fos
      expression. Importantly, we can now appreciate that Fos expression is often, but
      not always, associated with increased neuronal firing and vice versa. There are
      remaining gaps in our understanding of Fos in the nervous system. To date,
      knowledge of what Fos does after it is expressed is still limited. The transience
      of Fos expression after stimulation (especially if the stimulus is persistent)
      complicates design of experiments to assess the function of Fos and makes Fos of
      little value as a marker for long-term changes in neurone activity. In this
      regard, alternative approaches must be sought. Useful alternative approaches
      employed to date to monitor neuronal changes in activity include examination of
      (i) signal transduction intermediates (e.g. phosphorylated CREB); (ii)
      transcriptional/translational intermediates (e.g. heteronuclear RNA, messenger
      RNA (mRNA), prohormones); and (iii) receptor translocation. Another capitalizes
      on the fact that many neuroendocrine systems show striking stimulus-transcription
      coupling in the regulation of their transmitter or its synthetic enzymes.
      Together, as we move into the 21st Century, the use of multiple approach to study
      activity within neuroendocrine systems will further our understanding of these
      important systems.

PMID- 11963823
TI  - Long-term undernutrition followed by short-term refeeding effects on the
      corticotropin-releasing hormone containing neurones in the paraventricular
      nucleus: an immunohistochemical study in sheep.
AB  - The effect of nutritional level on the immunoreactivity of corticotropin
      releasing hormone (CRH) in neurones of the hypothalamic paraventricular nucleus
      was described in sheep, a ruminant, whose feeding strategy differs from that of
      monogastric species. Two groups of ewes were underfed (40%), or fed at
      maintenance (100%) for 167 days, after which one-half of each group was killed or
      ad libitum refed (at least 150% of maintenance) for 4 days before killing. The
      presence of CRH in the paraventricular nucleus was examined by
      immunohistochemistry. The number of CRH immunoreactive neurones was increased in
      underfed ewes, but without modification of the plasma concentration of cortisol,
      indicating that the rise of CRH was not released in the portal blood nor linked
      to the pituitary-adrenal axis. Refeeding did not modify significantly the number
      of CRH immunoreactive neurones in the nucleus although these neurones were
      increased, only in refed ewes that were previously underfed. These data differ
      from those for rats and mice where CRH expression is decreased or not modified by
      underfeeding which could reflect different effects of undernutrition on CRH
      immunoreactive neurones in monogastric compared to ruminants species.

PMID- 11963824
TI  - Effects of melanocortin receptor ligands on thyrotropin-releasing hormone
      release: evidence for the differential roles of melanocortin 3 and 4 receptors.
AB  - The hypothalamic melanocortin system is important in the central regulation of
      food intake and body weight. We have previously demonstrated that
      intracerebroventricular administration of alpha-melanocyte stimulating hormone
      (alpha-MSH), a nonselective MC3 and MC4 receptor agonist, stimulated plasma
      thyroid-stimulating hormone, and agouti-related protein (AgRP), an MC3 and MC4
      receptor antagonist, suppressed it. In this study, we investigated the effects of
      MC3 and MC4 receptor (MC3-R and MC4-R) selective agonists and antagonists on the
      release of thyrotropin-releasing hormone (TRH) from hypothalamic explants in
      vitro. alpha-MSH stimulated TRH release from the rat hypothalamic explants (alpha
      MSH 100 nm 230 +/- 22.9% basal, P < 0.005). In contrast, gamma 2-MSH, a selective
      MC3-R agonist, suppressed TRH release (gamma 2-MSH 10 microns 76.2 +/- 7.4%
      basal, P < 0.05). AgRP (83-132), a nonselective MC3/4-R antagonist, induced no
      change in TRH release whilst JKC-363 (cyclic [Mpr11, D-Nal14, Cys18, Asp22-NH2]
      beta-MSH 11-22), a selective MC4-R antagonist, suppressed it (JKC-363 10 nm 57.2
      +/- 11.5% basal, P < 0.05). Both AgRP (83-132) and JKC-363 blocked alpha-MSH
      stimulated TRH release but only AgRP (83-132) blocked the inhibitory effect of
      gamma 2-MSH on TRH release. These data suggest differential roles for the MC3 and
      MC4 receptors in TRH release; MC3-R agonism inhibiting and MC4-R agonism
      stimulating TRH release.

PMID- 11963825
TI  - Cerebral endothelial cells are a major source of adrenomedullin.
AB  - Adrenomedullin is a peptide hormone with multifunctional biological properties.
      Its most characteristic effects are the regulation of circulation and the control
      of fluid and electrolyte homeostasis through peripheral and central nervous
      system actions. Although adrenomedullin is a vasodilator of cerebral vasculature,
      and it may be implicated in the pathomechanism of cerebrovascular diseases, the
      source of adrenomedullin in the cerebral circulation has not been investigated
      thus far. We measured the secretion of adrenomedullin by radioimmunoassay and
      detected adrenomedullin mRNA expression by Northern blot analysis in primary
      cultures of rat cerebral endothelial cells (RCECs), pericytes and astrocytes. We
      also investigated the expression of specific adrenomedullin receptor components
      by reverse transcriptase-polymerase chain reaction and intracellular cAMP
      concentrations in RCECs and pericytes. RCECs had approximately one magnitude
      higher adrenomedullin production (135 +/- 13 fmol/10(5) cells per 12 h; mean +/-
      SD, n = 10) compared to that previously reported for other cell types. RCECs
      secreted adrenomedullin mostly at their luminal cell membrane. Adrenomedullin
      production was not increased by thrombin, lipopolysaccharide or cytokines, which
      are known inducers of adrenomedullin release in peripheral endothelial cells,
      although it was stimulated by astrocyte-derived factors. Pericytes had moderate,
      while astrocytes had very low basal adrenomedullin secretion. In vivo experiments
      showed that adrenomedullin plasma concentration in the jugular vein of rats was
      approximately 50% higher than that in the carotid artery or in the vena cava.
      Both RCECs and pericytes, which are potential targets of adrenomedullin in
      cerebral microcirculation, expressed adrenomedullin receptor components, and
      exhibited a dose-dependent increase in intracellular cAMP concentrations after
      exogenous adrenomedullin administration. Antisense oligonucleotide treatment
      significantly reduced adrenomedullin production by RCECs and tended to decrease
      intraendothelial cAMP concentrations. These findings may suggest an important
      autocrine and paracrine role for adrenomedullin in the regulation of cerebral
      circulation and blood-brain barrier functions. Cerebral endothelial cells are a
      potential source of adrenomedullin in the central nervous system, where
      adrenomedullin can also be involved in the regulation of neuroendocrine
      functions.

PMID- 11963826
TI  - Photoperiodic control of oestrous cycles in Syrian hamsters: mediation by the
      mediobasal hypothalamus.
AB  - To assess whether the mediobasal hypothalamus (MBH) is necessary for
      photoperiodic control of oestrous cycles and prolactin secretion, we tested
      intact female Syrian hamsters (controls) and those that had sustained unilateral
      or bilateral lesions of the MBH. All hamsters displayed 4-day oestrous cycles
      postoperatively in the long-day photoperiod (14 h light/day); control females and
      those with unilateral MBH damage ceased to undergo oestrous cycles approximately
      8 weeks after transfer to a short-day photocycle (10 h light/day), whereas 12 of
      15 females with bilateral MBH lesions continued to generate 4-day oestrous cycles
      throughout 22 weeks in short days. Serum prolactin concentrations were either
      undetectable or low in all hamsters 8 or 14 weeks after the transfer to short-day
      lengths, but increased above long-day baseline values by week 22. We conclude
      that melatonin-binding sites in the MBH mediate suppression of oestrous cycles
      but not prolactin secretion by short-day lengths; recovery of prolactin secretion
      in females during prolonged exposure to short-day lengths reflects development of
      refractoriness to melatonin in a substrate distinct from the MBH. These findings
      suggest that separate neural pathways mediate photoperiodic control of
      gonadotropin and prolactin secretion in female hamsters.

PMID- 11963827
TI  - Age-related changes in hypothalamic gonadotropin-releasing hormone and N-methyl-D
      aspartate receptor gene expression, and their regulation by oestrogen, in the
      female rat.
AB  - During reproductive ageing, the oestrous cycles of female rats become irregular
      and eventually cease. The mechanisms for reproductive senescence in rodents are
      believed to involve changes in hypothalamic neurones, including gonadotropin
      releasing hormone (GnRH) cells and their afferent inputs. In addition, effects of
      oestrogen on hypothalamic function may vary in animals of different ages. These
      issues were addressed using young (aged 4-5 months), middle-aged (12-14 months)
      and old (24-26 months) female Sprague-Dawley rats. Animals were ovariectomized
      and given oestrogen or vehicle replacement. They were killed and the preoptic
      area-anterior hypothalamus (POA-AH) and the medial basal hypothalamus-median
      eminence (MBH-ME) were dissected out, RNA extracted, and RNase protection assay
      used to quantify gene expression of several hypothalamic molecules. In the first
      experiment, GnRH RNA levels were measured in the POA-AH. No effects of ageing or
      oestrogen were observed on GnRH gene expression. This finding suggests that
      ageing and oestrogen may affect GnRH release from neuroterminals independently of
      de novo biosynthesis, and that this may involve other neurones that affect GnRH
      neurosecretory function. In the second experiment, we investigated changes in N
      methyl-D-aspartate (NMDA) receptor subunit mRNA levels. These receptors play an
      important regulatory role in mediating effects of glutamate on GnRH function, and
      are themselves regulated by oestrogen and ageing. NMDA receptor subunit (NR) 1,
      2a and 2b mRNA levels were quantified in the POA-AH and MBH-ME, the sites of GnRH
      perikarya and neuroterminals, respectively. In general, oestrogen had inhibitory
      effects on NR1 and NR2a, and differential effects on NR2b subunit mRNA levels.
      NMDA receptor subunit mRNA levels also changed during ageing: age-related
      decreases in NR1 mRNA occurred in the MBH-ME, and an age-related increase in NR2b
      mRNA occurred in the POA-AH. Taken together, these results demonstrate subunit-
      and region-specific changes in hypothalamic NMDA receptor subunit gene expression
      with oestrogen and ageing. These alterations could have implications for the
      physiological effects of glutamate on its NMDA receptor, and impact the
      regulation of reproductive and other neuroendocrine and autonomic functions by
      hypothalamic glutamatergic inputs.

PMID- 11963828
TI  - Regulation of glutamic acid decarboxylase 65 and 67 gene expression by ovarian
      steroids: identification of two functionally distinct populations of GABA
      neurones in the preoptic area.
AB  - GABA neurones in the preoptic area (POA) are critical for oestradiol (E2)
      dependent surge release of luteinizing hormone (LH); however, it is not clear
      which population(s) of POA GABA neurones is involved. The goals of the present
      studies were: (i) to determine whether E2 regulates GABA neurones similarly in
      two subdivisions of the POA that play a role in LH surge release, the rostral POA
      region that contains the organum vasculosum of the lamina terminalis (rPOA/OVLT),
      and the region containing the anteroventral periventricular nucleus (AVPV) and
      medial preoptic nucleus (MPN) and (ii) to determine whether GABA neurones in
      either or both regions exhibit temporal changes consistent with a role in the
      regulation of LH surge release. To accomplish these goals, we measured glutamic
      acid decarboxylase (GAD) 65 and 67 mRNA levels at several time points in
      ovariectomized (OVX), E2-treated OVX rats exhibiting LH surge release, and in E2
      treated OVX rats in which LH surge release was blocked by prior administration of
      progesterone (P4). Our findings demonstrate that, despite their close proximity,
      GABA neurones in the AVPV/MPN region are regulated differently from those in the
      rPOA/OVLT. Only neurones in the AVPV/MPN region show temporal changes in GAD 67
      mRNA expression that appear to be linked to positive-feedback effects of E2 on
      luteinizing hormone-releasing hormone (LHRH) and LH release. Our findings also
      indicate that a morning rise and an afternoon fall in GAD 67 mRNA levels marks
      two E2-dependent signals required for LHRH and LH surge release. Finally, our
      results suggest that there are distinct E2-induced signals to the rPOA/OVLT and
      AVPV/MPN regions and that these signals differentially regulate GAD 65 and 67
      gene expression.

PMID- 11963829
TI  - Photorefractoriness of immune function in male Siberian hamsters (Phodopus
      sungorus).
AB  - Short days induce multiple changes in reproductive and immune function in
      Siberian hamsters. Short-day reproductive inhibition in this species is regulated
      by an endogenous timing mechanism; after approximately 20 weeks in short days,
      neuroendocrine refractoriness to short-day patterns of melatonin develops,
      triggering spontaneous recrudescence of the reproductive system. It is unknown
      whether analogous mechanisms control immune function, or if photoperiodic changes
      in immune function are masked by prevailing photoperiod. In Experiment 1, 3 weeks
      of exposure to long days was not sufficient to induce long-day-like enhancement
      of in vitro lymphocyte proliferation in short-day adapted male Siberian hamsters.
      Experiment 2 tested the hypothesis that immunological photorefractoriness is
      induced by prolonged exposure to short days. Adult male hamsters were
      gonadectomized or sham-gonadectomized and housed in long (14 h light/day) or
      short (10 h light/day) photoperiods for 12, 32 or 40 weeks. Somatic and
      reproductive regression occurred after 12 weeks in short days, and spontaneous
      recrudescence was complete after 32-40 weeks in short days, indicative of somatic
      and reproductive photorefractoriness. In gonad-intact hamsters, 12 weeks of
      exposure to short days decreased the number of circulating granulocytes and
      increased the number of B-like lymphocytes. After 32 weeks in short days, these
      measures were restored to long-day values, indicative of photorefractoriness;
      castration eliminated these effects of photoperiod. In both intact and castrated
      hamsters, in vitro proliferation of splenic lymphocytes was inhibited by 12 weeks
      of exposure to short days. After 40 weeks in short days lymphocyte proliferation
      was restored to long-day values in intact hamsters, but remained suppressed in
      castrated hamsters. These results suggest that short-day-induced inhibition of
      lymphocyte function does not depend on gonadal regression, but that spontaneous
      recrudescence of this measure is dependent on gonadal recrudescence. In
      Experiment 3, in vitro treatment with melatonin enhanced basal proliferation of
      lymphocytes from male hamsters exposed to short days for 12 weeks, but had no
      effect on lymphocytes of photorefractory hamsters or long-day control hamsters.
      Lymphocytes of castrated hamsters were unresponsive to in vitro melatonin,
      suggesting that photoperiodic changes in gonadal hormone secretion may be
      required to activate mechanisms which permit differential responsiveness to
      melatonin depending on phase in the annual reproductive cycle. Together, these
      data indicate that, similar to the reproductive system, the immune system of male
      Siberian hamsters exhibits refractoriness to short days.

PMID- 11963830
TI  - Sucrose intake and corticosterone interact with cold to modulate ingestive
      behaviour, energy balance, autonomic outflow and neuroendocrine responses during
      chronic stress.
AB  - In adrenalectomized (ADX) rats, either corticosterone replacement or increased
      sucrose intake will restore body weight gain, uncoupling protein-1, fat depot
      mass, food intake and corticotropin-releasing factor mRNA expression to normal.
      Here, we tested the potential interactions between sucrose intake and circulating
      corticosterone on behavioural, metabolic, autonomic and neuroendocrine responses
      to the stress of cold. Rats were left intact, sham-ADX, or ADX and replaced with
      pellets that provided normal, basal (30%B) or high stress (100%B) constant
      circulating concentrations of corticosterone +/- sucrose. More calories were
      consumed in cold than at room temperature (RT), provided that corticosterone
      concentrations were elevated above mean daily basal values in cold. Neither
      increased sucrose nor increased chow ingestion occurred in cold if the rats were
      ADX and replaced with 30%B. However, sucrose drinking in this group markedly
      ameliorated other responses to cold. By contrast, ADX30%B rats not drinking
      sucrose fared poorly, and none of the metabolic or endocrine variables were
      similar to those in sham-ADX controls. ADX100%B group in cold, resembled intact
      rats without sucrose; however, this group was metabolically abnormal at RT. We
      conclude that drinking sucrose lowers stress-induced corticosterone secretion
      while reducing many responses to cold; elevated corticosterone concentrations in
      the stress-response range are essential for the normal integrated cold-induced
      responses to occur.

PMID- 11963832
TI  - Magnesium sulfate and prematurity.

PMID- 11963831
TI  - Expression of nm23-H1 protein in relation to myometrial invasion in complete
      hydatidiform moles.
AB  - OBJECTIVE: Although nm23-H1 protein expression has been related to invasion in
      many cancers, its expression and prognostic significance in complete hydatidiform
      moles has not yet been investigated. The search for biologic parameters in molar
      placentas, which are useful for identifying patients who show myometrial invasion
      of the tumor, is crucial. We examined the clinical significance of nm23-H1
      expression in complete hydatidiform mole. METHODS: Sections of 105 cases of
      complete hydatidiform moles (including 25 cases of invasive mole) and 95 cases of
      gestational age--matched normal placentas were immunohistochemically stained with
      anti-nm23-H1 antibody, which recognizes the nm23-H1/NDP kinase A gene product.
      RESULTS: Expression of nm23-H1 was detected in the cytotrophoblasts and
      syncytiotrophoblasts of molar placentas and normal placentas, whereas it was not
      detected in stromal tissue. Expression of nm23-H1 showed a negative relation to
      invasion, suggesting its use as a potential marker of myometrial invasion in
      complete hydatidiform moles. CONCLUSION: nm23-H1 expression could be used as a
      marker for accurate evaluation of myometrial invasion in complete hydatidiform
      mole.

PMID- 11963833
TI  - Association of type II apoptosis and 92-kDa type IV collagenase expression in
      human amniochorion in prematurely ruptured membranes with tumor necrosis factor
      receptor-1 expression.
AB  - OBJECTIVE: We assessed the presence of tumor necrosis factor receptor-1 (TNF-R1),
      apoptosis, and simultaneous expression of 92-kDa collagenase type IV (MMP-9) in
      samples of human chorioamnion from women with premature rupture of membranes
      (PROM). METHODS: Amniotic membranes from women who underwent normal labor,
      cesarean delivery, or had PROM at term were studied by immunohistochemistry for
      localization of TNF-R1 and R2. Transmission electron microscopy and DNA
      fragmentation analyses by agarose gel electrophoresis were performed to identify
      apoptosis characteristics. Zymography and in situ zymography were used to assess
      gelatinolytic activity. RESULTS: We found that TNF-R1 was abundant in membranes
      from subjects who had normal labor and very abundant in those who had PROM. By
      contrast TNF-R2 was abundant only in membranes from subjects who had cesarean
      delivery. Gelatinolytic activity was associated with extracellular matrix rather
      than cells and was higher in extracts from fetal membranes from PROM and normal
      labor than in extracts obtained from cesarean deliveries. Transmission electron
      microscopy of fetal membranes from PROM revealed ultrastructural characteristics
      in amnion epithelium consistent with type II apoptosis. DNA laddering in agarose
      gel electrophoresis corroborated results from DNA fragmentation. CONCLUSION:
      During PROM the fetal membranes undergo type II apoptosis and extracellular
      matrix degradation in association with TNF-R1 expression.

PMID- 11963834
TI  - Site-specific augmentation of amnion cyclooxygenase-2 and decidua vera
      phospholipase-A2 expression in labor: possible contribution of mechanical stretch
      and interleukin-1 to amnion prostaglandin synthesis.
AB  - OBJECTIVE: To investigate a possible site-specific augmentation of prostaglandin
      (PG) synthesis in the fetal membranes during labor. METHODS: We used reverse
      transcriptase-polymerase chain reaction or Western blot analysis to evaluate the
      expression of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-1, -2 (COX-1,
      -2), in both the upper and lower parts of the amnion, chorion laeve, and decidua
      vera tissues from term pregnant women before (n = 8) and after labor (n = 24).
      Prostaglandin E2 (PGE2) secretion from amnion-derived WISH cells was assessed
      using enzyme-linked immunosorbent assay after stimulation by cyclic mechanical
      stretching and interleukin-1 (IL-1). RESULTS: The expression of cPLA2 and COX-1
      and COX-2 mRNAs was detected in all samples examined. Western blot analysis
      revealed that COX-2 expression in the upper part of the amnion, chorion laeve,
      and decidua vera tissues after labor was 4.7-, 4.9-, and 3.7-fold higher than
      that before labor, respectively (P < .05 for all). The cPLA2 protein expression
      in the upper part of the amnion and chorion laeve tissues after labor was 14.0-
      and 8.8-fold higher than that before labor, respectively (P < .05 for both).
      Moreover, in specimens obtained after labor, the amnion COX-2 expression and the
      decidua vera cPLA2 expression in the lower part of the fetal membrane was 1.9-
      and 2.6-fold higher than the respective levels in the upper part (P < .05 for
      both). In an in vitro study, cyclic mechanical stretching significantly enhanced
      IL-1-augmented PGE2 secretion from WISH cells. CONCLUSION: In the lower part of
      the amnion and decidua vera tissues, adjacent to the dilating cervical canal, PG
      synthesis was upregulated site specifically after labor. Such enhancement of
      amnion PG synthesis might be regulated at least partly by IL-1 and cyclic
      distension.

PMID- 11963835
TI  - Temporal response of plasma erythropoietin to hemorrhage in the ovine fetus.
AB  - OBJECTIVE: In previous studies of ovine fetuses, plasma erythropoietin (EPO)
      concentration increased 10- to 20-fold at 24 hours after hemorrhage and returned
      toward normal at 48 hours. The present study in fetal sheep was designed to
      determine in detail the time course of the hemorrhage-induced changes in plasma
      EPO levels and explore the relationships among EPO concentration, blood oxygen
      tension, and hematocrit. METHODS: Chronically catheterized, late gestation ovine
      fetuses (n = 12) were hemorrhaged such that 40% of their blood volume was lost
      over 2 hours. Plasma EPO concentration, arterial blood gases, pH, and hematocrit
      were determined at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, and 36 hours after
      initiating the hemorrhage. Plasma EPO concentration was determined by
      radioimmunoassay. Statistical analyses included analysis of variance and least
      squares regression. RESULTS: Mean plasma EPO concentration increased
      significantly (2.3 +/- 0.5/+/- standard error of the mean/times basal values) at
      4 hours after initiating the hemorrhage, reached a maximum (33.8 +/- 12.9 times
      basal values) at 10-16 hours, and decreased to 50% of maximal values at 24 hours
      after hemorrhage. Hematocrit decreased rapidly during the 12 hours after
      hemorrhage (P < .0001), whereas arterial blood oxygen tension remained unchanged.
      The logarithm of EPO concentration was correlated with hematocrit (r = -0.74, P <
      .0001) but not with arterial blood oxygen tension. CONCLUSIONS: Blood EPO
      concentration began to increase at approximately 3-4 hours after the onset of
      hemorrhage. Further, EPO concentrations at 24 hours after hemorrhage represented
      only 50% of the maximal EPO response. The correlation between EPO and hematocrit
      suggests that blood oxygen content rather than oxygen tension is the more
      important stimulant for augmented EPO production after fetal hemorrhage.

PMID- 11963836
TI  - Fetal responses to intra-amniotic endotoxin in sheep.
AB  - OBJECTIVE: Our aim was to determine the acute physiologic effects of intra
      amniotic endotoxin administration in fetal sheep, and in particular, to determine
      whether intra-amniotic endotoxin causes an increase in fetal cortisol that could
      underlie the functional maturation of the fetal lungs previously reported in this
      model. METHODS: As in our previous experiments, ewes were randomly assigned to
      receive a single intra-amniotic injection of either endotoxin (20 mg, Escherichia
      coli [055:B5], n = 5) or saline (n = 5). Between 0.5 hours before endotoxin and
      168 hours after its administration, we measured maternal and fetal arterial
      pressures and heart rates; fetal and maternal blood samples were collected for
      measurement of blood gases, electrolytes, glucose and lactate concentrations,
      white cell counts (total and differential), and plasma cortisol. RESULTS: Fetal
      arterial carbon dioxide tension and lactate concentration were significantly
      elevated 6 and 12 hours after endotoxin but returned to pre-endotoxin levels by
      24 hours. Fetal plasma cortisol concentrations were significantly elevated at 4
      hours and peaked 24 hours after endotoxin, returning to control levels by 2 days.
      Fetal white cell counts initially decreased (4 hours) and then increased (after
      24 hours), becoming significantly elevated 6 days after treatment. Other fetal
      variables, and all measured maternal variables, were unaffected. CONCLUSIONS: Our
      data suggest that fetal sheep respond to intra-amniotic endotoxin with transient,
      mild physiologic alterations that follow a time course similar to inflammatory
      responses reported previously. The elevation in fetal cortisol is insufficient to
      be the cause of preterm lung maturation shown previously with this treatment.

PMID- 11963837
TI  - Neuroprotective effects of magnesium on metabolic disturbances in fetal
      hippocampal slices after oxygen-glucose deprivation: mediation by nitric oxide
      system.
AB  - OBJECTIVE: We investigated the effects of magnesium on metabolic disturbances in
      hippocampal slices prepared from fetal guinea pigs after oxygen-glucose
      deprivation (OGD). METHODS: Metabolic disturbances were assessed by measuring
      changes in energy metabolism and protein synthesis. In addition we determined
      cyclic guanosine monophosphate (cGMP) concentrations in the slices after OGD, as
      a measure of nitric oxide (NO) production, to clarify whether a possible
      neuroprotective effect of magnesium is mediated in part through the NO system.
      RESULTS: Twelve hours after oxygen-glucose deprivation, adenosine triphosphate
      (ATP) concentration and protein synthesis in the hippocampal slices were
      significantly reduced depending on the severity of OGD. A higher magnesium
      concentration in the incubation medium from 1.3 mM to 3.9 mM 2 hours before OGD
      significantly improved the recovery of ATP and protein synthesis, whereas
      treatment after OGD was ineffective. The cGMP concentrations increased
      dramatically in hippocampal slices 10 minutes after OGD, indicating a significant
      increase in NO production. When the concentration of magnesium in the artificial
      cerebrospinal fluid was increased 2 hours before OGD the rise in tissue levels of
      cGMP was considerably reduced. Again, treatment after OGD had no effect.
      CONCLUSION: We conclude that increasing magnesium concentration in the artificial
      cerebrospinal fluid before OGD alleviated metabolic disturbances in hippocampal
      slices from mature fetal guinea pigs, whereas treatment after OGD had no effect.
      This neuroprotective property of magnesium might be mediated in part through the
      inhibition of NO production shortly after OGD.

PMID- 11963838
TI  - Granulocyte macrophage colony-stimulating factor in adenomyosis and autologous
      endometrium.
AB  - OBJECTIVE: Granulocyte macrophage colony-stimulating factor (GM-CSF) has been
      related to macrophage recruitment and activation and has been identified in the
      human endometrium. We determined whether adenomyosis expresses GM-CSF, and if
      present, compared GM-CSF protein expression in adenomyosis with that in
      autologous endometrium. METHODS: We examined ectopic and eutopic endometrium from
      16 premenopausal women who had hysterectomies for abnormal uterine bleeding,
      pelvic pain, or uterine prolapse. Serial sections of premenopausal uteri
      containing endometrium and adenomyosis were analyzed by immunohistochemistry for
      GM-CSF ligand and receptor and CD68 macrophages. We analyzed the intensity of
      staining for GM-CSF ligand and receptor and macrophages in the glandular
      epithelium and stroma of adenomyosis and autologous endometrium. RESULTS: The GM
      CSF ligand localized primarily in the glandular epithelium and myometrium with
      only light stromal staining. Staining for GM-CSF ligand was significantly higher
      in adenomyotic glands compared with autologous endometrial glands (P = .002),
      especially during the secretory phase of the menstrual cycle. There were no
      statistical differences in the amount and intensity of staining of the GM-CSF
      receptor in adenomyosis and autologous endometrium. Adenomyotic tissue contained
      significantly more macrophages than matched autologous endometrium (P = .0004).
      CONCLUSIONS: Adenomyotic glandular epithelium had greater expression of the GM
      CSF ligand compared with autologous endometrium from premenopausal women, which
      indicates that GM-CSF may play a role in increasing the levels of activated
      macrophages in women with adenomyosis.

PMID- 11963839
TI  - Expression of soluble adhesion molecules in sera of women with stage III and IV
      endometriosis.
AB  - OBJECTIVE: To determine the effect of stage III and IV endometriosis on serum
      concentration of soluble intracellular adhesion molecule-1 (ICAM-1), vascular
      cellular adhesion molecule-1 (VCAM-1), and E-selectin. METHODS: Sera from women
      with laparoscopically proven stage III and IV endometriosis were analyzed for the
      presence of soluble ICAM-1, VCAM-1, and E-selectin using enzyme-linked
      immunosorbent assays. Concentrations of these molecules were compared with those
      of laparoscopically proven disease-free controls. RESULTS: When compared with
      controls, women with stage III and IV endometriosis had higher serum
      concentrations of soluble VCAM-1, lower serum concentration of soluble ICAM-1,
      and no difference in serum concentration of soluble E-selectin. CONCLUSION:
      Significant aberrations in levels of circulating adhesion molecules were found in
      women with stage III and IV endometriosis. These findings might shed light on the
      pathogenesis of endometriosis and be useful in the development of biochemical
      markers for disease stage.

PMID- 11963840
TI  - Development of high-performance and rapid immunoassay for model food allergen
      lysozyme using antibody-conjugated bacterial magnetic particles and fully
      automated system.
AB  - A high-performance and rapid chemiluminescence immunoassay for model food
      allergen lysozyme, one of the major allergenic components in egg white, using
      antibody-conjugated bacterial magnetic particles and a fully automated system was
      developed. This system contains a reaction station, tip rack, and an eight-tip
      pipettor that is able to attach and detach a strong magnet to the tip surface.
      The immunoreaction time was shortened to 5 min, and the assay was completed
      within 20 min. The lower detection limit for lysozyme was 10 ng/mL. This system
      can be used to perform 24 samples in 60 min within 10% coefficient of variation.

PMID- 11963841
TI  - Fermentation performance assessment of a genomically integrated xylose-utilizing
      recombinant of Zymomonas mobilis 39676.
AB  - In pH-controlled batch fermentations with pure sugar synthetic hardwood
      hemicellulose (1% [w/v] glucose and 4% xylose) and corn stover hydrolysate (8%
      glucose and 3.5% xylose) lacking acetic acid, the xylose-utilizing, tetracycline
      (Tc)-sensitive, genomically integrated variant of Zymomonas mobilis ATCC 39676
      (designated strain C25) exhibited growth and fermentation performance that was
      inferior to National Renewable Energy Laboratory's first-generation, Tc
      resistant, plasmid-bearing Zymomonas recombinants. With C25, xylose fermentation
      following glucose exhaustion was markedly slower, and the ethanol yield (based on
      sugars consumed) was lower, owing primarily to an increase in lactic acid
      formation. There was an apparent increased sensitivity to acetic acid inhibition
      with C25 compared with recombinants 39676:pZB4L, CP4:pZB5, and ZM4:pZB5. However,
      strain C25 performed well in continuous fermentation with nutrient-rich synthetic
      corn stover medium over the dilution range 0.03-0.06/h, with a maximum process
      ethanol yield at D = 0.03/h of 0.46 g/g and a maximum ethanol productivity of 3
      g/(L x h). With 0.35% (w/v) acetic acid in the medium, the process yield at D =
      0.04/h dropped to 0.32 g/g, and the maximum productivity decreased by 50% to 1.5
      g/(L x h). Under the same operating conditions, rec Zm ZM4:pZB5 performed better;
      however, the medium contained 20 mg/L of Tc to constantly maintain selective
      pressure. The absence of any need for antibiotics and antibiotic resistance genes
      makes the chromosomal integrant C25 more compatible with current regulatory
      specifications for biocatalysts in large-scale commercial operations.

PMID- 11963842
TI  - Comparative ethanol productivities of different Zymomonas recombinants fermenting
      oat hull hydrolysate.
AB  - Iogen Corporation of Ottawa, Canada, has recently built a 50 t/d biomass-to
      ethanol demonstration plant adjacent to its enzyme production facility. Iogen has
      partnered with the University of Toronto to test the C6/C5 cofermentation
      performance characteristics of National Renewable Energy Laboratory's
      metabolically engineered Zymomonas mobilis using its biomass hydrolysates. In
      this study, the biomass feedstock was an agricultural waste, namely oat hulls,
      which was hydrolyzed in a proprietary two-stage process involving pretreatment
      with dilute sulfuric acid at 200-250 degrees C, followed by cellulase hydrolysis.
      The oat hull hydrolysate (OHH) contained glucose, xylose, and arabinose in a mass
      ratio of about 8:3:0.5. Fermentation media, prepared from diluted hydrolysate,
      were nutritionally amended with 2.5 mL/L of corn steep liquor (50% solids) and
      1.2 g/L of diammonium phosphate. The estimated cost for large-scale ethanol
      production using this minimal level of nutrient supplementation was 4.4cents/gal
      of ethanol. This work examined the growth and fermentation performance of xylose
      utilizing, tetracycline-resistant, plasmid-bearing, patented, recombinant Z.
      mobilis cultures: CP4:pZB5, ZM4:pZB5, 39676:pZB4L, and a hardwood prehydrolysate
      adapted variant of 39676:pZB4L (designated as the "adapted" strain). In pH-stat
      batch fermentations with unconditioned OHH containing 6% (w/v) glucose, 3%
      xylose, and 0.75% acetic acid, rec Zm ZM4:pZB5 gave the best performance with a
      fermentation time of 30 h, followed by CP4:pZB5 at 48 h, with corresponding
      volumetric productivities of 1.4 and 0.89 g/ (L x h), respectively. Based on the
      available glucose and xylose, the process ethanol yield for both strains was 0.47
      g/g (92% conversion efficiency). At 48 h, the process yield for rec Zm
      39676:pZB4L and the adapted strain was 0.32 and 0.34 g/g, respectively. None of
      the test strains was able to ferment arabinose. Acetic acid tolerance appeared to
      be a major determining factor in cofermentation performance.

PMID- 11963843
TI  - Isolation of Magnetospirillum magneticum AMB-1 mutants defective in bacterial
      magnetic particle synthesis by transposon mutagenesis.
AB  - Nonmagnetic mutants of Magnetospirillum magneticum AMB-1 were recovered following
      mini-Tn5 transposon mutagenesis. Transconjugants with kanamycin resistance were
      obtained at a frequency of 2.7 x 10(-7) per recipient. Of 3327 transconjugants,
      62 were defective for bacterial magnetic particle (BMP) synthesis. The frequency
      of independent transposition events for nonmagnetic mutants was about 1.4% in
      transconjugants. Further analysis of DNA sequences flanking transposon by
      inverted polymerase chain reaction allowed isolation of at least 10 genes or DNA
      sequences involved in BMP synthesis in M. magneticum AMB-1.

PMID- 11963844
TI  - Synthesis of bacterial magnetic particles during cell cycle of Magnetospirillum
      magneticum AMB-1.
AB  - We investigated the relationship between the synthesis of bacterial magnetic
      particles (BMPs) and the transcription of magA gene-encoding iron transport
      protein using synchronous culture of Magnetospirillum magneticum AMB-1.
      Synchronously cultured cells were subjected to transmission electron microscopic
      observation and fluorescence in situ hybridization. The average number of BMPs
      slowly increased in the cell with increasing cell size. A sharp increase in BMPs
      occurred just before cell division and resulted in maximum BMP production of 30
      particles/cell. The transcription of magA was regulated immediately before and
      after cell division.

PMID- 11963845
TI  - Overexpression of glucose-6-phosphate dehydrogenase in genetically modified
      Saccharomyces cerevisiae.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) (EC 1.1.1.49) is an abundant enzyme in
      Saccharomyces cerevisiae. This enzyme is of great interest as an analytical
      reagent because it is used in a large number of quantitative assays. A strain of
      S. cerevisiae was genetically modified to improve G6PD production during aerobic
      culture. The modifications are based on cloning the G6PD sequence under the
      control of promoters that are upregulated by the carbon source used for yeast
      growth. The results showed that S. cerevisiae acquired from a commercial source
      and the same strain produced by aerobic cultivation under controlled conditions
      provided very similar G6PD. However, G6PD production by genetically modified S.
      cerevisiae produced very high enzyme activity and showed to be the most effective
      procedure to obtain glucose-6-phosphate dehydrogenase. As a consequence, the cost
      of producing G6PD can be significantly reduced by using strains that contain
      levels of G6PD up to 14-fold higher than the level of G6PD found in commercially
      available strains.

PMID- 11963847
TI  - Utilization of cyanobacteria in photobioreactors for orthophosphate removal from
      water.
AB  - The effectiveness of photosynthetic free-living and polyurethane foam (PU)
      immobilized Anabaena variabilis cells for removal of orthophosphate (P) from
      water in batch cultures and in a photobioreactor was studied. Immobilization in
      PU foams was found to have a positive effect on P uptake by cyanobacteria in
      batch cultures. The efficiency of P uptake by immobilized cells was higher than
      by free-living cells. A laboratory scale photobioreactor was constructed for
      removal of P from water by the immobilized cyanobacteria. The photobioreactor was
      designed so that the growth medium (water) from a reservoir was pumped through a
      photobioreactor column with immobilized cyanobacteria and back to the reservoir.
      This created a closed system in which it was possible to measure P uptake. No
      leakage of cells into the photobioreactor medium reservoir was observed during
      the operation. The immobilized cells incorporated into a photobioreactor column
      removed P continuously for about 15 d. No measurable uptake was demonstrated
      after this period. Orthophosphate uptake efficiency of 88-92% was achieved by the
      photobioreactor.

PMID- 11963846
TI  - Biosorption of heavy metals by bacteria isolated from activated sludge.
AB  - Twelve aerobic bacteria from activated sludge were isolated and identified. These
      included both Gram-positive (e.g., Bacillus) and Gram-negative (e.g.,
      Pseudomonas) bacteria. The biosorption capacity of these strains for three
      different heavy metals (copper, nickel, and lead) was determined at pH 5.0 and
      initial metal concentration of 100 mg/L. Among these 12 isolates, Pseudomonas
      pseudoalcaligenes was selected for further investigation owing to its high metal
      biosorption capacity. The lead and copper biosorption of this strain followed the
      Langmuir isotherm model quite well with maximum biosorption capacity (q(max))
      reaching 271.7mg of Pb2+/g of dry cell and 46.8 mg of Cu2+/g of dry cell at pH
      5.0. Study of the effect of pH on lead and copper removal indicated that the
      metal biosorption increased with increasing pH from 2.0 to 7.0. A mutual
      inhibitory effect was observed in the lead-copper system because the presence of
      either ion affected the sorption capacity of the other. Unequal inhibitions were
      observed in all the nickel binary systems. The increasing order of affinity of
      the three metals toward P. pseudoalcaligenes was Ni < Cu < Pb. The metal
      biosorptive potential of these isolates, especially P. pseudoalcaligenes, may
      have possible applications in the removal and recovery of metals from industrial
      effluents.

PMID- 11963848
TI  - Enhancement of the conversion of toluene by Pseudomonas putida F-1 using organic
      cosolvents.
AB  - Pseudomonas putida F-1 (ATCC700007) was used as a model organism in stirred tank
      reactors to study conversion enhancement of poorly soluble substrates by organic
      cosolvents. After a literature study, silicone oil was used as a solvent system
      to enhance the mass transfer rate. To study the benefits of the organic solvent
      addition, batch experiments were conducted in two side-by-side fermentation
      vessels (experimental and control) at three different levels of silicone oil (10,
      30, and 50%). Results showed that the presence of silicone oil resulted in a 100%
      increase in the toluene mass transfer compared to the control. Experiments in
      continuous stirred-tank reactors showed that improved conversion could be
      obtained at higher agitation rates.

PMID- 11963849
TI  - Effect of temperature on biofiltration of nitric oxide.

PMID- 11963850
TI  - Biodegradation of formaldehyde by a formaldehyde-resistant bacterium isolated
      from seawater.
AB  - A formaldehyde-tolerant bacterium designated as a DM-2 strain was used to
      biodegrade formaldehyde. The cells, precultivated in the presence of 400 ppm of
      formaldehyde, were able to degrade formaldehyde in a minimal medium supplemented
      with up to 400 ppm of formaldehyde in the presence of 3% NaCl. The rate of
      formaldehyde degradation achieved in this study was 45 ppm/h when the DM-2
      culture's optical density at 660 nm was 1.2.

PMID- 11963851
TI  - Dissemination of catabolic plasmids among desiccation-tolerant bacteria in soil
      microcosms.
AB  - The dissemination of catabolic plasmids was compared to bioaugmentation by strain
      inoculation in microcosm experiments. When Rhodococcus erythropolis strain T902,
      bearing a plasmid with trichloroethene and isopropylbenzene degradation pathways,
      was used as the inoculum, no transconjugant was isolated but the strain remained
      in the soil. This plasmid had a narrow host range. Pseudomonas putida strain C8S3
      was used as the inoculum in a second approach. It bore a broad host range
      conjugative plasmid harboring a natural transposon, RP4::Tn4371, responsible for
      biphenyl and 4-chlorobiphenyl degradation pathways. The inoculating population
      slowly decreased from its original level (10(6) colony-forming units [CFU]/g of
      dry soil) to approx 3 x 10(2) CFU/g of dry soil after 3 wk. Transconjugant
      populations degrading biphenyl appeared in constant humidity soil (up to 2 x
      10(3) CFU/g) and desiccating soil (up to 10(4) CFU/g). The feasibility of plasmid
      dissemination as a bioaugmentation technique was demonstrated in desiccating
      soils. The ecologic significance of desiccation in bioaugmentation was
      demonstrated: it upset the microbial ecology and the development of
      transconjugants.

PMID- 11963852
TI  - Genetic improvement of poplar feedstock quality for ethanol production.
AB  - Opportunities for matching chemical and physical properties of woody feedstocks
      to ethanol production process requirements via genetic improvement have long been
      recognized. Exploitation is now feasible owing to advances in trait measurement,
      breeding, and gene transfer technologies. Poplar genetic parameters are favorable
      largely for reducing lignin and increasing cellulose contents and specific
      gravity. Transgenic poplars with decreased lignin and increased cellulose
      contents, but otherwise normal growth and development, have been produced via
      genetic transformation. The long-standing debate on feasibility has thus become
      one of when, not if, designer varieties will become available.

PMID- 11963853
TI  - Bioprocessing research.

PMID- 11963854
TI  - Ethanol production from lignocellulosic byproducts of olive oil extraction.
AB  - The recent implementation of a new two-step centrifugation process for extracting
      olive oil in Spain has substantially reduced water consumption, thereby
      eliminating oil mill wastewater. However, a new high sugar content residue is
      still generated. In this work the two fractions present in the residue (olive
      pulp and fragmented stones) were assayed as substrate for ethanol production by
      the simultaneous saccharification and fermentation (SSF) process. Pretreatment of
      fragmented olive stones by sulfuric acid-catalyzed steam explosion was the most
      effective treatment for increasing enzymatic digestibility; however, a
      pretreatment step was not necessary to bioconvert the olive pulp into ethanol.
      The olive pulp and fragmented olive stones were tested by the SSF process using a
      fed-batch procedure. By adding the pulp three times at 24-h intervals, 76% of the
      theoretical SSF yield was obtained. Experiments with fed-batch pretreated olive
      stones provided SSF yields significantly lower than those obtained at standard
      SSF procedure. The preferred SSF conditions to obtain ethanol from olives stones
      (61% of theoretical yield) were 10% substrate and addition of cellulases at 15
      filter paper units/g of substrate.

PMID- 11963855
TI  - Continuous countercurrent extraction of hemicellulose from pretreated wood
      residues.
AB  - Two-stage dilute acid pretreatment followed by enzymatic cellulose hydrolysis is
      an effective method for obtaining high sugar yields from wood residues such as
      softwood forest thinnings. In the first-stage hydrolysis step, most of the
      hemicellulose is solubilized using relatively mild conditions. The soluble
      hemicellulosic sugars are recovered from the hydrolysate slurry by washing with
      water. The washed solids are then subjected to more severe hydrolysis conditions
      to hydrolyze approx 50% of the cellulose to glucose. The remaining cellulose can
      further be hydrolyzed with cellulase enzyme. Our process simulation indicates
      that the amount of water used in the hemicellulose recovery step has a
      significant impact on the cost of ethanol production. It is important to keep
      water usage as low as possible while maintaining relatively high recovery of
      soluble sugars. To achieve this objective, a prototype pilot-scale continuous
      countercurrent screw extractor was evaluated for the recovery of hemicellulose
      from pretreated forest thinnings. Using the 274-cm (9-ft) long extractor,
      solubles recoveries of 98, 91, and 77% were obtained with liquid-to-insoluble
      solids (L/IS) ratios of 5.6, 3.4, and 2.1, respectively. An empirical equation
      was developed to predict the performance of the screw extractor. This equation
      predicts that soluble sugar recovery above 95% can be obtained with an L/IS ratio
      as low as 3.0.

PMID- 11963856
TI  - Enzymatic hydrolysis of ammonia-treated sugar beet pulp.
AB  - Sugar beet pulp is a carbohydrate-rich coproduct generated by the table sugar
      industry. Beet pulp has shown promise as a feedstock for ethanol production using
      enzymes to hydrolyze polymeric carbohydrates and engineered bacteria to ferment
      sugars to ethanol. In this study, sugar beet pulp underwent an ammonia
      pressurization depressurization (APD) pretreatment in which the pulp was exploded
      by the sudden evaporation of ammonia in a reactor vessel. APD was found to
      substantially increase hydrolysis efficiency of the cellulose component, but when
      hemicellulose- and pectin-degrading enzymes were added, treated pulp hydrolysis
      was no better than the untreated control.

PMID- 11963857
TI  - Ethanol production in a membrane bioreactor: pilot-scale trials in a corn wet
      mill.
AB  - Pilot plant trials were conducted in a corn wet mill with a 7000-L membrane
      recycle bioreactor (MRB) that integrated ceramic microfiltration membranes in a
      semi-closed loop configuration with a stirred-tank reactor. Residence times of
      7.5-10 h with ethanol outputs of 10-11.5% (v/v) were obtained when the cell
      concentration was 60-100 g/L dry wt of yeast, equivalent to about 10(9)-10(10)
      cells/mL. The performance of the membrane was dependent on the startup mode and
      pressure management techniques. A steady flux of 70 L/(m2 x h) could be
      maintained for several days before cleaning was necessary. The benefits of the
      MRB include better productivity; a clear product stream containing no
      particulates or yeast cells, which should improve subsequent stripping and
      distillation operations; and substantially reduced stillage handling. The capital
      cost of the MRB is $21-$34/(m3 x yr) ($0.08-$0.13/[gal x yr]) of ethanol
      capacity. Operating cost, including depreciation, energy, membrane replacement,
      maintenance, labor, and cleaning, is $4.5-9/m3 ($0.017-$0.034/gal) of ethanol.

PMID- 11963858
TI  - Cellulase recovery via membrane filtration.
AB  - A combined sedimentation and membrane filtration process was investigated for
      recycling cellulase enzymes in the biomass-to-ethanol process. In the first
      stage, lignocellulose particles longer than approx 50 microm were removed by
      means of sedimentation in an inclined settler. Microfiltration was then utilized
      to remove the remaining suspended solids. Finally, the soluble cellulase enzymes
      were recovered by ultrafiltration. The permeate fluxes obtained in
      microfiltration and ultrafiltration were approx 400 and 80 L/(m2 x h),
      respectively. A preliminary economic analysis shows that the cost benefit of
      enzyme recycling may be as much as 18 cents/gal of ethanol produced, provided
      that 75% of the enzyme is recycled in active form.

PMID- 11963859
TI  - Feedstocks production, modification, and characterization.

PMID- 11963860
TI  - Effect of yeast extract on growth kinetics of Monascus purpureus.
AB  - Growth kinetics and red pigment production of Monascus purpureus CCT 3802 was
      studied. A reproducible inoculum with extremely dispersed hyphae for bioreactor
      runs was obtained through a two-step cultivation in a shaker. First, the spores
      were cultivated in a complex medium rendering a suspension of vegetative cells.
      In the second step these cells were grown in a semisynthetic medium. Two types of
      media were employed in the bioreactor runs: a semisynthetic (glucose, salts, and
      yeast extract), and a synthetic, without yeast extract. The inclusion of yeast
      extract, caused an increase in cell yield on glucose (Yx/s) as high as 40%. Also,
      yeast extract probably yielded a higher proportion of red pigment associated with
      the cell, relative to the synthetic medium. On the other hand, cells grown on the
      synthetic medium were slightly higher producers of red soluble pigments.

PMID- 11963861
TI  - Severity function describing the hydrolysis of xylan using carbonic acid.
AB  - Beech wood derived xylan to hydrolyzed to predominantly xylose monomer units
      after exposure to hot, compressed liquid water saturated with carbon dioxide.
      Similar treatment without CO2 saturation resulted in only minor hydrolysis and a
      smaller fraction of monomers among the hydrolysis products. Severity of the
      hydrolysis reaction was correlated to reaction time, temperature, and carbon
      dioxide partial pressure and followed a function similar to those used to
      characterize mineral acid systems. Results from parallel hydrolysis experiments
      with an aqueous system and a very dilute sulfuric acid system allowed an
      approximation of the dissociation constant of carbonic acid in the temperature
      range of 170-230 degrees C. Results suggest that carbonic acid may be a viable
      reagent for promoting hydrolysis without mineral acids, especially in the case of
      a bioprocessing plant that produces carbon dioxide.

PMID- 11963862
TI  - Cellulose hydrolysis under extremely low sulfuric acid and high-temperature
      conditions.
AB  - The kinetics of cellulose hydrolysis under extremely low acid (ELA) conditions
      (0.07 wt%) and at temperatures >200 degrees C was investigated using batch
      reactors and bed-shrinking flow-through (BSFT) reactors. The maximum yield of
      glucose obtained from batch reactor experiments was about 60% for alpha
      cellulose, which occurred at 205 and 220 degrees C. The maximum glucose yields
      from yellow poplar feedstocks were substantially lower, falling in the range of
      26-50%. With yellow poplar feedstocks, a large amount of glucose was unaccounted
      for at the latter phase of the batch reactions. It appears that a substantial
      amount of released glucose condenses with nonglucosidic substances in liquid. The
      rate of glucan hydrolysis under ELA was relatively insensitive to temperature in
      batch experiments for all three substrates. This contradicts the traditional
      concept of cellulose hydrolysis and implies that additional factors influence the
      hydrolysis of glucan under ELA. In experiments using BSFT reactors, the glucose
      yields of 87.5, 90.3, and 90.8% were obtained for yellow poplar feedstocks at
      205, 220, and 235 degrees C, respectively. The hydrolysis rate for glucan was
      about three times higher with the BSFT than with the batch reactors. The
      difference of observed kinetics and performance data between the BSFT and the
      batch reactors was far above that predicted by the reactor theory.

PMID- 11963863
TI  - A hybrid neural network algorithm for on-line state inference that accounts for
      differences in inoculum of Cephalosporium acremonium in fed-batch fermentors.
AB  - One serious difficulty in modeling a fermentative process is the forecasting of
      the duration of the lag phase. The usual approach to model biochemical reactors
      relies on first-principles, unstructured mathematical models. These models are
      not able to take into account changes in the process response caused by different
      incubation times or by repeated fedbatches. To overcome this problem, we have
      proposed a hybrid neural network algorithm. Feedforward neural networks were used
      to estimate rates of cell growth, substrate consumption, and product formation
      from on-line measurements during cephalosporin C production. These rates were
      included in the mass balance equations to estimate key process variables:
      concentrations of cells, substrate, and product. Data from fed-batch fermentation
      runs in a stirred aerated bioreactor employing the microorganism Cephalosporium
      acremonium ATCC 48272 were used. On-line measurements strongly related to the
      mass and activity of the cells used. They include carbon dioxide and oxygen
      concentrations in the exhausted gas. Good results were obtained using this
      approach.

PMID- 11963865
TI  - Kinetics of ethanol fermentation with high biomass concentration considering the
      effect of temperature.
AB  - A model of ethanol fermentation considering the effect of temperature was
      developed and validated. Experiments were performed in a temperature range from
      28 to 40 degrees C in continuous mode with total cell recycling using a
      tangential microfiltration system. The developed model considered substrate,
      product and biomass inhibition, as well as an active cell phase (viable) and an
      inactive (dead) phase. The kinetic parameters were described as functions of
      temperature.

PMID- 11963864
TI  - Detoxification of lignocellulose hydrolysates with ion-exchange resins.
AB  - Lignocellulose hydrolysates contain fermentation inhibitors causing decreased
      ethanol production. The inhibitors include phenolic compounds, furan aldehydes,
      and aliphatic acids. One of the most efficient methods for removing inhibiting
      compounds prior to fermentation is treatment of the hydrolysate with ion-exchange
      resins. The performance and detoxification mechanism of three different resins
      were examined: an anion exchanger, a cation exchanger, and a resin without
      charged groups (XAD-8). A dilute acid hydrolysate of spruce was treated with the
      resins at pH 5.5 and 10.0 prior to ethanolic fermentation with Saccharomyces
      cerevisiae. In addition to the experiments with hydrolysate, the effect of the
      resins on selected model compounds, three phenolics (vanillin, guaiacol, and
      coniferyl aldehyde) and two furan aldehydes (furfural and hydroxymethyl
      furfural), was determined. The cation exchanger increased ethanol production, but
      to a lesser extent than XAD-8, which in turn was less effective than the anion
      exchanger. Treatment at pH 10.0 was more effective than at pH 5.5. At pH 10.0,
      the anion exchanger efficiently removed both anionic and uncharged inhibitors,
      the latter by hydrophobic interactions. The importance of hydrophobic
      interactions was further indicated by a substantial decrease in the concentration
      of model compounds, such as guaiacol and furfural, after treatment with XAD-8.

PMID- 11963866
TI  - Fermentation of xylose into acetic acid by Clostridium thermoaceticum.
AB  - For optimum fermentation, fermenting xylose into acetic acid by Clostridium
      thermoaceticum (ATCC 49707) requires adaptation of the strain to xylose medium.
      Exposed to a mixture of glucose and xylose, it preferentially consumes xylose
      over glucose. The initial concentration of xylose in the medium affects the final
      concentration and the yield of acetic acid. Batch fermentation of 20 g/L of
      xylose with 5 g/L of yeast extract as the nitrogen source results in a maximum
      acetate concentration of 15.2 g/L and yield of 0.76 g of acid/g of xylose. Corn
      steep liquor (CLS) is a good substitute for yeast extract and results in similar
      fermentation profiles. The organism consumes fructose, xylose, and glucose from a
      mixture of sugars in batch fermentation. Arabinose, mannose, and galactose are
      consumed only slightly. This organism loses viability on fed-batch operation,
      even with supplementation of all the required nutrients. In fed-batch
      fermentation with CSL supplementation, D-xylulose (an intermediate in the xylose
      metabolic pathway) accumulates in large quantities.

PMID- 11963867
TI  - Heat transfer considerations in design of a batch tube reactor for biomass
      hydrolysis.
AB  - Biologic conversion of inexpensive and abundant sources of cellulosic biomass
      offers a low-cost route to production of fuels and commodity chemicals that can
      provide unparalleled environmental, economic, and strategic benefits. However,
      low-cost, high-yield technologies are needed to recover sugars from the
      hemicellulose fraction of biomass and to prepare the remaining cellulose fraction
      for subsequent hydrolysis. Uncatalyzed hemicellulose hydrolysis in flow-through
      systems offers a number of important advantages for removal of hemicellulose
      sugars, and it is believed that oligomers could play an important role in
      explaining why the performance of flow-through systems differs from uncatalyzed
      steam explosion approaches. Thus, an effort is under way to study oligomer
      formation kinetics, and a small batch reactor is being applied to capture these
      important intermediates in a closed system that facilitates material balance
      closure for varying reaction conditions. In this article, heat transfer for batch
      tubes is analyzed to derive temperature profiles for different tube diameters and
      assess the impact on xylan conversion. It was found that the tube diameter must
      be <0.5 in. for xylan hydrolysis to follow the kinetics expected for a uniform
      temperature system at typical operating conditions.

PMID- 11963868
TI  - Measurement of bubble size distribution in protein foam fractionation column
      using capillary probe with photoelectric sensors.
AB  - Bubble size is a key variable for predicting the ability to separate and
      concentrate proteins in a foam fractionation process. It is used to characterize
      not only the bubble-specific interfacial area but also coalescence of bubbles in
      the foam phase. This article describes the development of a photoelectric method
      for measuring the bubble size distribution in both bubble and foam columns for
      concentrating proteins. The method uses a vacuum to withdraw a stream of gas
      liquid dispersion from the bubble or foam column through a capillary tube with a
      funnel-shaped inlet. The resulting sample bubble cylinders are detected, and
      their lengths are calculated by using two pairs of infrared photoelectric sensors
      that are connected with a high-speed data acquisition system controlled by a
      microcomputer. The bubble size distributions in the bubble column 12 and 1 cm
      below the interface and in the foam phase 1 cm above the interface are obtained
      in a continuous foam fractionation process for concentrating ovalbumin. The
      effects of certain operating conditions such as the feed protein concentration,
      superficial gas velocity, liquid flow rate, and solution pH are investigated. The
      results may prove to be helpful in understanding the mechanisms controlling the
      foam fractionation of proteins.

PMID- 11963869
TI  - Effect of a natural contaminant on foam fractionation of bromelain.
AB  - Foam fractionation is a simple, inexpensive method for separating and purifying
      proteins. Typically, a dilute bromelain solution with a pH ranging from 2.0 to
      7.0 foams very well when bubbles are introduced into a foam fractionation column.
      It was observed, however, that the dilute enzyme solution only foamed between
      approximately pH 2.0 and 3.0 when the inner wall of the fractionation column was
      coated with a natural contaminant (okra residue). We studied the separation ratio
      and the protein mass recovery to explore the effect of a natural antifoaming
      agent on the foam fractionation of a dilute bromelain solution. The control
      variables used in this process were the initial bulk solution pH, which ranged
      from 2.0 to 7.0, and the superficial air velocity, which varied between 1.7 and
      6.2 cm/s.

PMID- 11963870
TI  - Application of factorial design to study of heavy metals biosorption by waste
      biomass from beverage distillery.
AB  - A full factorial design leading to 20 sets of sorption runs was conducted to
      study the influence of four variables (bleaching earth and biomass
      concentrations, pH, and sorption time) on the iron, nickel, and chromium removal
      from stainless steel effluent using waste biomass from a beverage industry.
      Similar factor effects and interactions were found for each metal involved in
      this biosorption study, and the main factors were pH (positive effect) and
      biomass concentration (negative effect). Response surface methodology was adopted
      and an empirical linear polynomial model constructed on the basis of the specific
      uptake (mg of metal/g of biomass as dryweight) for each metal species. Under
      optimized process conditions (pH 4.0, biomass concentration of 2.0 g/L, absence
      of Celite), uptake values of 155 mg of Fe/g, 38 mg of Cr/g, and 0.4 mg of Ni/g
      were achieved after 3 h. This corresponded to a reduction in heavy metals
      concentration of approx 94% for Cr, 57% for Fe, and 25% for Ni.

PMID- 11963871
TI  - Model compound studies: influence of aeration and hemicellulosic sugars on
      xylitol production by Candida tropicalis.
AB  - The influence of other hemicellulosic sugars (arabinose, galactose, mannose, and
      glucose), oxygen limitation, and initial xylose concentration on the fermentation
      of xylose to xylitol was investigated using experimental design methodology.
      Oxygen limitation and initial xylose concentration had strong influences on
      xylitol production by Candida tropicalis ATCC 96745. Under semiaerobic
      conditions, xylitol yield was highest (0.62 g/g), whereas under aerobic
      conditions volumetric productivity was highest (0.90 g/[L x h]). In the presence
      of glucose, xylose utilization was strongly repressed and sequential sugar
      utilization was observed. Ethanol produced from the glucose caused a 50%
      reduction in xylitol yield when the ethanol concentration exceeded 30 g/L. When
      complex synthetic hemicellulosic sugars were fermented, glucose was initially
      consumed followed by a simultaneous uptake of the other sugars. The highest
      xylitol yield (0.84 g/g) and volumetric productivity (0.49 g/[L x h]) were
      obtained for substrates containing high arabinose and low glucose and mannose
      contents.

PMID- 11963872
TI  - Nitrification and denitrification processes for biologic treatment of industrial
      effluents.
AB  - Nitrification process performance was evaluated using a three-phase fluidized-bed
      bioreactor. A synthetic effluent was used for this experiment containing 180-230
      mg/L of chemical oxygen demand (COD), 25-30 mg/L of N-NH4+, 12 to 13 mg/L of
      total phosphorous, and micronutrients. The bioreactor used for denitrification
      behaved as completely mixed. The results indicate that the nitrification process
      was efficient, reaching efficiencies of about 98%. The best results related to
      the efficiency of the denitrification process were obtained when the processes
      were supplemented with the carbon source. The results indicated an efficiency of
      86-98% COD removal.

PMID- 11963873
TI  - Removal and recovery of copper (II) ions by bacterial biosorption.
AB  - Studies were conducted to investigate the removal and recovery of copper (II)
      ions from aqueous solutions by Micrococcus sp., which was isolated from a local
      activated sludge process. The equilibrium of copper biosorption followed the
      Langmuir isotherm model very well with a maximum biosorption capacity (q(max)) of
      36.5 mg of Cu2+/g of dry cell at pH 5.0 and 52.1 mg of Cu2+/g of dry cell at pH
      6.0. Cells harvested at exponential growth phase and stationary phase showed
      similar biosorption characteristics for copper. Copper uptake by cells was
      negligible at pH 2.0 and then increased rapidly with increasing pH until 6.0. In
      multimetal systems, Micrococcus sp. exhibited a preferential biosorption order:
      Cu approximate to Pb > Ni approximate to Zn. There is virtually no interference
      with copper uptake by Micrococcus sp. from solutions bearing high concentrations
      of Cl-, SO4(2-), and NO3- (0-500 mg/L). Sulfuric acid (0.05 M) was the most
      efficient desorption medium, recovering >90% of the initial copper sorbed. The
      copper capacity of Micrococcus sp. remained unchanged after five successive
      sorption and desorption cycles. Immobilization of Micrococcus sp. in 2% calcium
      alginate and 10% polyacrylamide gel beads increased copper uptake by 61%. Biomass
      of Micrococcus sp. may be applicable to the development of potentially cost
      effective biosorbent for removing and recovering copper from effluents.

PMID- 11963874
TI  - Production of biosurfactant from a new and promising strain of Pseudomonas
      aeruginosa PA1.
AB  - The Pseudomonas aeruginosa PA1 strain, isolated from the water of oil production
      in Sergipe, Northeast Brazil, was evaluated as a potential rhamnolipid type of
      biosurfactant producer. The production of biosurfactants was investigated using
      different carbon sources (n-hexadecane, paraffin oil, glycerol, and babassu oil)
      and inoculum concentrations (0.0016-0.008 g/L). The best results were obtained
      with glycerol as the substrate and an initial cell concentration of 0.004 g/L. A
      C:N ratio of 22.8 led to the greatest production of rhamnolipids (1700 mg/L) and
      efficiency (1.18 g of rhamnolipid/g of dry wt).

PMID- 11963875
TI  - Cassava starch maltodextrinization/monomerization through thermopressurized
      aqueous phosphoric acid hydrolysis.
AB  - Kinetic conditions were established for the depolymerization of cassava starch
      for the production of maltodextrins and glucose syrups. Thin-layer chromatography
      and high-performance liquid chromatography analyses corroborated that the proper
      H3PO4 strength and thermopressurization range (e.g., 142-170 degrees C; 2.8-6.8
      atm) can be successfully explored for such hydrolytic purposes of native starch
      granules. Because phosphoric acid can be advantageously maintained in the
      hydrolysate and generates, after controlled neutralization with ammonia, the
      strategic nutrient triplet for industrial fermentations (C, P, N), this
      pretreatment strategy can be easily recognized as a recommended technology for
      hydrolysis and upgrading of starch and other plant polysaccharides. Compared to
      the classic catalysts, the mandatory desalting step (chloride removal by
      expensive anion-exchange resin or sulfate precipitation as the calcium-insoluble
      salt) can be avoided. Furthermore, properly diluted phosphoric acid is well known
      as an allowable additive in several popular soft drinks such as colas since its
      acidic feeling in the mouth is compatible and synergistic with both natural and
      artificial sweeteners. Glycosyrups from phosphorolyzed cassava starch have also
      been upgraded to high-value single-cell protein such as the pigmented yeast
      biomass of Xanthophyllomyces dendrorhous (Phaffia rhodozyma), whose astaxanthin
      (diketo-dihydroxy-beta-carotene) content may reach 0.5-1.0 mg/g of dry yeast
      cell. This can be used as an ideal complement for animal feeding as well as a
      natural staining for both fish farming (meat) and poultry (eggs).

PMID- 11963876
TI  - Industrial chemicals.

PMID- 11963877
TI  - The effect of pretreatments on surfactin production from potato process effluent
      by Bacillus subtilis.
AB  - Pretreatments of low-solids potato process effluent were tested for their
      potential to increase surfactin yield. Pretreatments included heat, removal of
      starch particulates, and acid hydrolysis. Elimination of contaminating vegetative
      cells was necessary for surfactin production. After autoclaving, 0.40 g/L of
      surfactin was produced from the effluent in 72 h, vs 0.24 g/L in the purified
      potato starch control. However, surfactin yields per carbon consumed were 76%
      lower from process effluent. Removal of starch particulates had little effect on
      the culture. Acid hydrolysis decreased growth and surfactant production, except
      0.5 wt% acid, which increased the yield by 25% over untreated effluent.

PMID- 11963878
TI  - Twenty years of trials, tribulations, and research progress in bioethanol
      technology: selected key events along the way.
AB  - The projected cost of ethanol production from cellulosic biomass has been reduced
      by almost a factor of four over the last 20 yr. Thus, it is now competitive for
      blending with gasoline, and several companies are working to build the first
      plants. However, technology development faced challenges at all levels. Because
      the benefits of bioethanol were not well understood, it was imperative to clarify
      and differentiate its attributes. Process engineering was invaluable in focusing
      on promising opportunities for improvements, particularly in light of budget
      reductions, and in tracking progress toward a competitive goal. Now it is vital
      for one or more commercial projects to be successful, and improving our
      understanding of process fundamentals will reduce the time and costs for
      commercialization. Additionally, the cost of bioethanol must be cut further to be
      competitive as a pure fuel in the open market, and aggressive technology advances
      are required to meet this target.

PMID- 11963879
TI  - Production of bacterial cellulose from alternate feedstocks.
AB  - Production of bacterial cellulose by Acetobacter xylinum ATCC 10821 and 23770 in
      static cultures was tested from unamended food process effluents. Effluents
      included low-solids (LS) and high-solids (HS) potato effluents, cheese whey
      permeate (CW), or sugar beet raffinate (CSB). Strain 23770 produced 10% less
      cellulose from glucose than did strain 10821 and diverted more glucose to
      gluconate. Unamended HS, CW, and CSB were unsuitable for cellulose production by
      either strain, and LS was unsuitable for production by strain 10821. However,
      strain 23770 produced 17% more cellulose from LS than from glucose, indicating
      that unamended LS could serve as a feedstock for bacterial cellulose.

PMID- 11963880
TI  - Fourier transform infrared quantitative analysis of sugars and lignin in
      pretreated softwood solid residues.
AB  - Hydrolysates were obtained from dilute sulfuric acid pretreatment of whole-tree
      softwood forest thinnings and softwood sawdust. Mid-infrared (IR) spectra were
      obtained on sample sets of wet washed hydrolysates, and 45 degrees C vacuum-dried
      washed hydrolysates, using a Fourier transform infrared (FTIR) spectrophotometer
      equipped with a diamond-composite attenuated total reflectance (ATR) cell.
      Partial least squares (PLS) analysis of spectra from each sample set was
      performed. Regression analyses for sugar components and lignin were generated
      using results obtained from standard wet chemical and high-performance liquid
      chromatography methods. The correlation coefficients of the predicted and
      measured values were >0.9. The root mean square standard error of the estimate
      for each component in the residues was generally within 2 wt% of the measured
      value except where reported in the tables. The PLS regression analysis of the wet
      washed solids was similar to the PLS regression analysis on the 45 degrees C
      vacuum-dried sample set. The FTIR-ATR technique allows mid-IR spectra to be
      obtained in a few minutes from wet washed or dried washed pretreated biomass
      solids. The prediction of the solids composition of an unknown washed pretreated
      solid is very rapid once the PLS method has been calibrated with known standard
      solid residues.

PMID- 11963881
TI  - Production of polyhydroxybutyrate by Bacillus species isolated from municipal
      activated sludge.
AB  - Plastic wastes are considered to be severe environmental contaminants causing
      waste disposal problems. Widespread use of biodegradable plastics is one of the
      solutions, but it is limited by high production cost. Biologic wastewater
      treatment generates large quantities of biomass as activated sludge. Only a few
      reports focus on the potential of utilizing resident Bacillus species from
      activated sludge in polyhydroxbutyrate (PHB) production as well as the production
      of PHB from food wastes. They have attractive properties such as short generation
      time, absence of endotoxins, and secretion of both amylases and proteinases that
      can well utilize food wastes for nutrients, which can further reduce the cost of
      production of polyhydroxyalkanoates (PHAs). Two PHA-producing strains, HF-1 and
      HF-2, were isolated from activated sludge. HF-1 outperformed HF-2 in terms of
      growth and PHB production in hydrolyzed soy and malt wastes. The isolated
      bacteria was characterized by DNA sequence alignment. Cell extracts of HF-1 were
      also compared to Bacillus megaterium cell extracts on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The biopolymers accumulated were analyzed by
      gas chromatography, nuclear magnetic resonance, and Fourier transform infrared
      methods.

PMID- 11963882
TI  - Characterization of bioconversion of fumarate to succinate by alginate
      immobilized Enterococcus faecalis RKY1.
AB  - In this study, the immobilization characteristics of Enterococcus faecalis RKY1
      for succinate production were examined. At first, three natural polymers--agar,
      kappa-carrageenan, and sodium alginate--were tried as immobilizing matrices.
      Among these, sodium alginate was selected as the best gel for immobilization of
      E. faecalis RKY1. Efficient conditions for immobilization were established to be
      with a 2% (w/v) sodium alginate solution and 2-mm-diameter bead. The
      bioconversion characteristics of the immobilized cells at various pH values and
      temperatures were examined and compared with those of free cells. The optimum pH
      and temperature of the immobilized cells were the same as for free cells, 7.0 and
      38 degrees C respectively, but the conversion ratio was higher by immobilization
      for all the other pH and temperature conditions tested. When the seed volume of
      the immobilized cells was adjusted to 10% (v/v), 30 g/L of fumarate was
      completely converted to succinate (0.973 g/g conversion ratio) after 12 h. In
      addition, the immobilized cells maintained a conversion ratio of >0.95 g/g during
      4 wk of storage at 4 degrees C in a 2% (w/v) CaCl2 solution. In repetitive
      bioconversion experiments, the activity of the immobilized cells decreased
      linearly according to the number of times of reuse.

PMID- 11963883
TI  - Modeling and simulation of cephalosporin C production in a fed-batch tower-type
      bioreactor.
AB  - Immobilized cell utilization in tower-type bioreactor is one of the main
      alternatives being studied to improve the industrial bioprocess. Other
      alternatives for the production of beta-lactam antibiotics, such as a
      cephalosporin C fed-batch process in an aerated stirred-tankbioreactor with free
      cells of Cephalosporium acremonium, or a tower-type bioreactor with immobilized
      cells of this fungus, have proven to be more efficient than the batch process. In
      the fed-batch process, it is possible to minimize the catabolite repression
      exerted by the rapidly utilization of carbon sources (such as glucose) in the
      synthesis of antibiotics by utilizing a suitable flow rate of supplementary
      medium. In this study, several runs for cephalosporin C production, each lasting
      200 h, were conducted in a fed-batch tower-type bioreactor using different
      hydrolyzed sucrose concentrations. For this study's model, modifications were
      introduced to take into account the influence of supplementary medium flow rate.
      The balance equations considered the effect of oxygen limitation inside the
      bioparticles. In the Monod-type rate equations, cell concentrations, substrate
      concentrations, and dissolved oxygen were included as reactants affecting the
      bioreaction rate. The set of differential equations was solved by the numerical
      method, and the values of the parameters were estimated by the classic nonlinear
      regression method following Marquardt's procedure with a 95% confidence interval.
      The simulation results showed that the proposed model fit well with the
      experimental data, and based on the

PMID- 11963884
TI  - Influence of culture conditions on lipopeptide production by Bacillus subtilis.
AB  - Bacillus subtilis produces various families of lipopeptides with different
      homologous compounds. To produce "new molecules" with improved activities and to
      select strains that produced a reduced number of homologs or isomers, we studied
      the effects of different media on the nature of the synthesis of fatty acid
      chains for each lipopeptide family. This study focused on two B. subtilis strains
      cultivated in flasks. Optimized medium for lipopeptide production and Landy
      medium modified by replacing glutamic acid with other alpha-amino acids were
      used. We found that the intensity of production of homologous compounds depends
      on the strain and the culture medium. Analysis of these lipopeptides by high
      performance liquid chromatography showed that the strain B. subtilis NT02 yielded
      various homologous compounds when cultivated in Landy medium (L-Glu), but
      primarily one homologous product in high relative amounts when cultivated in the
      optimized medium. Mass spectrometric analysis and determination of the amino acid
      composition of this molecule enabled us to identify it as Bacillomycine L c15.

PMID- 11963885
TI  - Mathematical modeling of controlled-release kinetics of herbicides in a dynamic
      water-bath system.
AB  - Release of herbicides from lignin-based formulations follows a diffusion
      controlled mechanism. For mathematical modeling of diffusive transport, the
      conventional approach is to assume sink conditions at both surfaces of polymeric
      matrix. This boundary condition proved to be inadequate to describe experimental
      data obtained in a water dynamic bath system. However, satisfactory descriptions
      for this system were obtained when a stagnant unstirred layer of herbicide
      solution was used as the boundary condition. The adequacy of the model
      incorporating this new boundary condition was statistically tested using the
      Fisher test at a confidence level of 95% and plotting the residual distribution.

PMID- 11963886
TI  - Do cellulose binding domains increase substrate accessibility?
AB  - This article provides an overview of various theories proposed during the past
      five decades to describe the enzymatic hydrolysis of cellulose highlighting the
      major shifts that these theories have undergone. It also describes the effect of
      the cellulose-binding domain (CBD) of an exoglucanase/xylanase from bacterium
      Cellulomonas fimi on the enzymatic hydrolysis of Avicel. Pretreatment of Avicel
      with CBDCex at 4 and 37 degrees C as well as simultaneous addition of CBDCex to
      the hydrolytic enzyme (Celluclast, Novo, Nordisk) reduced the initial rate of
      hydrolysis owing to irreversible binding of CBD proteins to the substrate's
      binding sites. Nonetheless, near complete hydrolysis was achieved even in the
      presence of CBDCex. Protease treatment of both pure and CBDCex-treated Avicel
      reduced the substrates' hydrolyzability, perhaps owing to proteolysis of the
      hydrolyzing enzyme (Celluclast) by the residual Proteinase K remaining in the
      substrate. Better protocols for complete removal of CBD proteins from the
      substrate need to be developed to investigate the effect of CBD adsorption on
      cellulose digestibility.

PMID- 11963887
TI  - Enzymatic processes and enzyme production.

PMID- 11963888
TI  - Cobalt activation of Bacillus BR449 thermostable nitrile hydratase expressed in
      Escherichia coli.
AB  - Expression of nitrile hydratase enzymes utilized in a new "green" process for
      acrylamide production has proven difficult in Escherichia coli owing to lack of a
      cobalt transport system to introduce the required cobalt ion into this host. We
      describe the expression of a thermostable nitrile hydratase from a moderate
      thermophile Bacillus sp. BR449 in E. coliin which the cobalt required for enzyme
      activation is introduced by incubation of the apoenzyme in the presence of Co++
      ion at 50 degrees C, yielding active and thermostable enzyme.

PMID- 11963889
TI  - Effect of agitation and aeration on production of hexokinase by Saccharomyces
      cerevisiae.
AB  - A batch culture of Saccharomyces cerevisiae for the production of hexokinase was
      carried out in a 5-L fermentor containing 3 L of culture medium, which was
      inoculated with cell suspension (about 0.7 g/L), and left fermenting at 35
      degrees C and pH 4.0. The aeration and agitation were adjusted to attain k(L)a
      values of 15, 60, 135, and 230 h(-1). The highest hexokinase productivity (754.6
      U/[L x h]) and substrate-cell conversion yield (0.21 g/g) occurred for a k(L)a of
      60 h(-1). Moreover, the formation of hexokinase and cell growth are coupled
      events, which is in accordance with the constitutive character of this enzyme.
      Hexokinase formation for kLa > 60 h(-1) was not enhanced probably owing to
      saturation of the respiratory pathway by oxygen.

PMID- 11963890
TI  - Comparison of catalytic properties of free and immobilized cellobiase novozym
      188.
AB  - The enzyme cellobiase from Novo was immobilized in controlled pore silica
      particles by covalent binding with the silane-glutaraldehyde method with protein
      and activity yields of 67 and 13.7%, respectively. The activity of the free
      enzyme (FE) and immobilized enzyme (IE) was determined with 2 g/L of cellobiose,
      from 40 to 75 degrees C at pH 3.0-7.0 for FE and from 40 to 70 degrees C at pH
      2.2-7.0 for IE. At pH 4.8 the maximum specific activity for the FE and IE
      occurred at 65 degrees C: 17.8 and 2.2 micromol of glucose/(min x mg of protein),
      respectively. For all temperatures the optimum pH observed for FE was 4.5 whereas
      for IE it was shifted to 3.5. The energy of activation was 11 kcal/mol for FE and
      5 kcal/mol for IE at pH 4.5-5, showing apparent diffusional limitation for the
      latter. Thermal stability of the FE and IE was determined with 2 g/L of
      cellobiose (pH 4.8) at temperatures from 40 to 70 degrees C for FE and 40 to 75
      degrees C for IE. Free cellobiase maintained its activity practically constant
      for 240 min at temperatures up to 55 degrees C. The IE has shown higher
      stability, retaining its activity in the same test up to 60 degrees C. Half-life
      experimental results for FE were 14.1, 2.1, and 0.17 h at 60, 65, and 70 degrees
      C, respectively, whereas IE at the same temperatures had half-lives of 245, 21.3,
      and 2.9 h. The energy of thermal deactivation was 80.6 kcal/mol for the free
      enzyme and 85.2 kcal/mol for the IE, suggesting stabilization by immobilization.

PMID- 11963892
TI  - Bleachability and characterization by Fourier transform infrared principal
      component analysis of Acetosolv pulps obtained from sugarcane bagasse.
AB  - Sugarcane bagasse Acetosolv pulps were bleached by xylanase and the pulps
      classified by using Fourier transform infrared (FTIR) spectroscopy and principal
      component analysis (PCA). Pulp was treated with xylanase for 4-8 hwith stirring
      at 30 degrees C. Some samples were further extracted with NaOH for 1 h at 65
      degrees C. FTIR spectra were recorded directly from the dried pulp samples by
      using the diffuse reflectance technique. Reduction in kappa number of 69% was
      obtained after sequence xylanase (4 h)-alkaline extraction. During bleaching the
      viscosity decreased only 12%. FTIR-PCA showed that the first three principal
      components (PCs) explained more than 90% of the total variance of the pulp
      spectra. PC2 x PC1 plot showed that the points related to pulps from sequence
      xylanase (4 h)-alkaline extraction are different from the other. This group is
      enlarged by plotting PC3 x PC1 or PC3x PC2 containing all pulps submitted to
      alkaline extraction. PC2 and PC3 are the principal factor for differentiation of
      the pulps. These PCs suffer influence of the ester bands (1740 and 1244 cm(-1)).
      On the other hand, the pulps bleached only with xylanase could not be
      differentiated from the nonbleached pulps.

PMID- 11963891
TI  - Influence of operating conditions and vessel size on oxygen transfer during
      cellulase production.
AB  - The production of low-cost cellulase enzyme is a key step in the development of
      an enzymatic-based process for conversion of lignocellulosic biomass to ethanol.
      Although abundant information is available on cellulase production, little of
      this work has examined oxygen transfer. We investigated oxygen transfer during
      the growth of Trichoderma reesei, a cellulase-producing microorganism, on soluble
      and insoluble substrates in vessel sizes from 7 to 9000 L. Oxygen uptake rates
      and volumetric mass transfer coefficients (kLa) were determined using mass
      spectroscopy to measure off gas composition. Experimentally measured kLa values
      were found to compare favorably with a kLa correlation available in the
      literature for a non-Newtonian fermentation broth during the period of heavy cell
      growth.

PMID- 11963893
TI  - Characterization of cyclodextrin glycosyltransferase from Bacillus firmus strain
      no. 37.
AB  - The enzyme cyclodextrin glycosyltransferase (CGTase), EC 2.4.1.19, which produces
      cyclodextrins (CDs) from starch, was obtained from Bacillusfirmus strain no. 37
      isolated from Brazilian soil and characterized in the soluble form using as
      substrate 100 g/L of maltodextrin in 0.05 M Tris-HCl buffer, 5 mM CaCl2, and
      appropriate buffers. Enzymatic activity and its activation energy were determined
      as a function of temperature and pH. The activation energy for the production of
      beta- and gamma-CD was 7.5 and 9.9 kcal/mol, respectively. The energy of
      deactivation was 39 kcal/mol. The enzyme showed little thermal deactivation in
      the temperature range of 35-60 degrees C, and Arrhenius-type equations were
      obtained for calculating the activity, deactivation, and half-life as a function
      of temperature. The molecular weight of the enzyme was determined by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis, giving 77.6 kDa. Results for
      CGTase activity as a function of temperature gave maximal activity for the
      production of beta-CD at 65 degrees C, pH 6.0, and 71.5 mmol of beta-CD/(min x mg
      of protein), whereas for gamma-CD it was 9.1 mmol of gamma-CD/(min mg of protein)
      at 70 degrees C and pH 8.0. For long contact times, the best use of the enzymatic
      activity occurs at 60 degrees C or at a lower temperature, and the reaction pH
      may be selected to increase the yield of a desired CD.

PMID- 11963894
TI  - Physiological aspects involved in production of xylanolytic enzymes by deep-sea
      hyperthermophilic archaeon Pyrodictium abyssi.
AB  - Xylanases (EC 3.2.1.8) catalyze the hydrolysis of xylan, the major constituent of
      hemicellulose. The use of these enzymes could greatly improve the overall
      economics of processing lignocellulosic materials for the generation of liquid
      fuels and chemicals. The hyperthermophilic archaeon Pyrodictium abyssi, which was
      originally isolated from marine hot abyssal sites, grows optimally at 97 degrees
      C and is a prospective source of highly thermostable xylanase. Its endoxylanase
      was shown to be highly thermostable (over 100 min at 105 degrees C) and active
      even at 110 degrees C. The growth of the deep-sea archaeon P. abyssi was
      investigated using different culture techniques. Among the carbohydrates used,
      beech wood xylan, birch wood glucuronoxylan and the arabinoxylan from oats pelt
      appeared to be good inducers for endoxylanase and beta-xylosidase production. The
      highest production of arabinofuranosidase, however, was detected in the cell
      extracts after growth on xylose and pyruvate, indicating that the intermediate of
      the tricarboxylic acid cycle acted as a nonrepressing carbon source for the
      production of this enzyme. Electron microscopic studies did not show a
      significant difference in the cell surface (e.g., xylanosomes) when P. abyssi
      cells were grown on different carbohydrates. The main kinetic parameters of the
      organism have been determined. The cell yield was shown to be very low owing to
      incomplete substrate utilization, but a very high maximal specific growth rate
      was determined (micromax = 0.0195) at 90 degrees C and pH 6.0. We also give
      information on the problems that arise during the fermentation of this
      hyperthermophilic archaeon at elevated temperatures.

PMID- 11963895
TI  - Preliminary kinetic characterization of xylose reductase and xylitol
      dehydrogenase extracted from Candida guilliermondii FTI 20037 cultivated in
      sugarcane bagasse hydrolysate for xylitol production.
AB  - Candida guilliermondii FTI 20037 was cultured in sugarcane bagasse hydrolysate
      supplemented with 2.0 g/L of (NH4)2SO4, 0.1 g/L of CaCl2 x 2H2O, and 20.0 g/L of
      rice bran at 35 degrees C; pH 4.0; agitation of 300 rpm; and aeration of 0.4,
      0.6, or 0.8 vvm. The high xylitol production (20.0 g/L) and xylose reductase (XR)
      activity (658.8 U/mg of protein) occurred at an aeration of 0.4 vvm. Under this
      condition, the xylitol dehydrogenase (XD) activity was low. The apparent K(M) for
      XR and XD against substrates and cofactors were as follows: for XR, 6.4 x 10(-2)M
      (xylose) and 9.5 x 10(-3) mM (NADPH); for XD, 1.6 x 10(-1)M (xylitol) and 9.9 x
      10(-2) mM (NAD+). Because XR requires about 10-fold less xylose and cofactor than
      XD for the condition in which the reaction rate is half of the Vmax, some
      interference on the overall xylitol production by the yeast could be expected.

PMID- 11963896
TI  - Xylanase production by Aspergillus awamori in solid-state fermentation and
      influence of different nitrogen sources.
AB  - The use of purified xylan as a substrate for bioconversion into xylanases
      increases the cost of enzyme production. Consequently, there have been attempts
      to develop a bioprocess to produce such enzymes using different lignocellulosic
      residues. Filamentous fungi have been widely used to produce hydrolytic enzymes
      for industrial applications, including xylanases, whose levels in fungi are
      generally much higher than those in yeast and bacteria. Considering the
      industrial importance of xylanases, the present study evaluated the use of milled
      sugarcane bagasse, without any pretreatment, as a carbon source. Also, the effect
      of different nitrogen sources and the C:N ratio on xylanase production by
      Aspergillus awamori were investigated, in experiments carried out in solid-state
      fermentation. High extracellular xylanolytic activity was observed on cultivation
      of A. awamori on milled sugarcane bagasse and organic nitrogen sources (45 IU/mL
      for endoxylanase and 3.5 IU/mL for beta-xylosidase). Endoxylanase and beta
      xylosidase activities were higher when sodium nitrate was used as the nitrogen
      source, when compared with peptone, urea, and ammonium sulfate at the optimized
      C:N ratio of 10:1. The use of yeast extract as a supplement to the these nitrogen
      sources resulted in considerable improvement in the production of xylanases,
      showing the importance of this organic nitrogen source on A. awamori metabolism.

PMID- 11963897
TI  - Kinetic and mass transfer parameters of maltotriose hydrolysis catalyzed by
      glucoamylase immobilized on macroporous silica and wrapped in pectin gel.
AB  - Kinetic and mass transport parameters were estimated for maltotriose hydrolysis
      using glucoamylase immobilized on macroporous silica and wrapped in pectin gel at
      30 degrees C. Free enzyme assays were used to obtain the intrinsic kinetic
      parameters of a Michaelis-Menten equation, with product inhibition by glucose.
      The uptake method, based on transient experimental data, was employed in the
      estimation of mass transfer parameters. Effective diffusivities of maltotriose in
      pectin gel were estimated by fitting a classical diffusion model to experimental
      data of maltotriose diffusion into particles of pectin gel in the absence of
      silica. The effective diffusivities of maltotriose in silica were obtained after
      fitting a bidisperse model to experimental data of maltotriose hydrolysis using
      glucoamylase immobilized in silica and wrapped in pectin gel.

PMID- 11963898
TI  - Selection of stabilizing additive for lipase immobilization on controlled pore
      silica by factorial design.
AB  - Candida rugosa lipase was covalently immobilized on silanized controlled pore
      silica (CPS) previously activated with glutaraldehyde in the presence of several
      additives to improve the performance of the immobilized form in long-term
      operation. Proteins (albumin and lecithin) and organic molecules (beta
      cyclodextrin and polyethylene glycol [PEG]-1500) were added during the
      immobilization procedure, and their effects are reported and compared to the
      behavior of the immobilized biocatalyst in the absence (lacking) of additive. The
      selection of the most efficient additive at different lipase loadings (150-450
      U/g of dry support) was performed by experimental design. Two 22 full factorial
      designs with two repetitions at the center point were employed to evaluate the
      immobilization yield. A better stabilizing effect was found when small amounts of
      albumin or PEG-1500 were added simultaneously to the lipase onto the support. The
      catalytic activity had a maximum (193 U/mg) for lipase loading of 150 U/g of dry
      support using PEG-1500 as the stabilizing additive. This immobilized system was
      used to perform esterification reactions under repeated batch cycles (for the
      synthesis of butyl butyrate as a model). The half-life of the lipase immobilized
      on CPS in the presence of PEG-1500 was found to increase fivefold compared with
      the control (immobilized lipase on CPS without additive).

PMID- 11963899
TI  - Production of oxychemicals from precipitated hardwood lignin.
AB  - Lignin is a major byproduct in the biomass-to-ethanol process. The lignin
      produced from acid treatment of biomass has characteristics suitable for further
      conversion to organic chemicals. It is free of contaminants and has a relatively
      low molecular weight. In this study, catalytic oxidative conversion of the acid
      soluble lignin precipitated from acid hydrolysates of hardwood was investigated.
      The process is based on aqueous alkaline oxidation of lignin with dissolved O2 in
      the presence of Fe3+ and Cu2+ catalysts at moderate reaction temperatures (160
      180 degrees C). Aromatic aldehydes, ketones, and organic acids are found to be
      the primary products identifiable on extraction with ether. The combined weight
      yield of the total ether extractable products is about 20-25% of the initial
      lignin. The yield of the aldehydes (vanillin + syringaldehyde) is in the vicinity
      of 15% with an additional 3 to 4% of aromatic ketones. The yields of aldehydes
      plus ketones observed in this work far exceeded those obtainable from the
      conventional alkaline air oxidation of spent sulfite liquors. This article also
      provides comprehensive batch reaction data on conversion and product
      distribution.

PMID- 11963900
TI  - Screening of variables in beta-xylosidase recovery using cetyl trimethyl ammonium
      bromide reversed micelles.
AB  - Beta-xylosidase recovery by micelles using cetyl trimethyl ammonium bromide
      (CTAB) cationic surfactant was verified under different experimental conditions.
      A 2(5-1) fractional factorial design with center points was employed to verify
      the influence of the following factors on enzyme extraction: pH (x1), CTAB
      concentration (x2), electrical conductivity (x3), hexanol concentration (x4), and
      butanol concentration (x). Statistical analysis of the results shows that of the
      five variables studied only hexanol and electrical conductivity did not have
      significant effects on the recovery of beta-xylosidase. The other factors had
      significant effects in increasing order: (x1) > (x2) > (x5). The model predicts a
      recovery value of about 45%, which is similar to that obtained experimentally
      (43.5%).

PMID- 11963902
TI  - Kinetic studies of lipase from Candida rugosa: a comparative study between free
      and immobilized enzyme onto porous chitosan beads.
AB  - The search for an inexpensive support has motivated our group to undertake this
      work dealing with the use of chitosan as matrix for immobilizing lipase. In
      addition to its low cost, chitosan has several advantages for use as a support,
      including its lack of toxicity and chemical reactivity, allowing easy fixation of
      enzymes. In this article, we describe the immobilization of Candida rugosa lipase
      onto porous chitosan beads for the enzymatic hydrolysis of olive oil. The binding
      of the lipase onto the support was performed by physical adsorption using hexane
      as the dispersion medium. A comparative study between free and immobilized lipase
      was conducted in terms of pH, temperature, and thermal stability. A slightly
      lower value for optimum pH (6.0) was found for the immobilized form in comparison
      with that attained for the soluble lipase (7.0). The optimum reaction temperature
      shifted from 37 degrees C for the free lipase to 50 degrees C for the chitosan
      lipase. The patterns of heat stability indicated that the immobilization process
      tends to stabilize the enzyme. The half-life of the soluble free lipase at 55
      degrees C was equal to 0.71 h (Kd = 0.98 h(-1)), whereas for the immobilized
      lipase it was 1.10 h (Kd = 0.63 h(-1)). Kinetics was tested at 37 degrees C
      following the hydrolysis of olive oil and obeys the Michaelis-Menten type of rate
      equation. The Km was 0.15 mM and the Vmax was 51 micromol/(min x mg), which were
      lower than for free lipase, suggesting that the apparent affinity toward the
      substrate changes and that the activity of the immobilized lipase decreases
      during the course of immobilization.

PMID- 11963901
TI  - Activity of xylose reductase from Candida mogii grown in media containing
      different concentrations of rice straw hydrolysate.
AB  - Xylose reductase (XR) activity was evaluated in extracts of Candida mogii grown
      in media containing different concentrations of rice straw hydrolysate. Results
      of XR activity were compared to xylitol production and a similar behavior was
      observed for these parameters. Highest values of specific production and
      productivity were found for xylose reductase (35 U/g of cell and 0.97 U/[g of
      cell x h], respectively) and for xylitol (5.63 g/g of cell and 0.13 g/[g of cell
      x h]) in fermentation conducted in medium containing 49.2 g of xylose/L. The
      maximum value of XR:XD ratio (1.82) was also calculated under this initial xylose
      concentration with 60 h of fermentation.

PMID- 11963903
TI  - Extraction by reversed micelles of the intracellular enzyme xylose reductase.
AB  - Xylose reductase enzyme (EC 1.1.1.21) produced by Candida guilliermondii in
      sugarcane bagasse was extracted by reversed micelles of N-benzyl-N-dodecyl-N-bis
      (2-hydroxyethyl) ammonium chloride cationic surfactant. An experimental design
      was employed to evaluate the influences of the following factors on the enzyme
      extraction: temperature, cosolvent, and surfactant concentration. A model was
      used to represent the enzyme recovery and fit of the experimental data. The
      extraction yielded a total recovery of 130%, and the purity increased 4.8-fold.
      This study demonstrates that liquid-liquid extraction by reversed micelles is a
      process able to recover and increase the enzymatic activity and purity of XR
      produced by C. guilliermondii.

PMID- 11963904
TI  - Controlled hydrolysis of cheese whey proteins using trypsin and alpha
      chymotrypsin.
AB  - This study examined the production of protein hydrolysates with controlled
      composition from cheese whey proteins. Cheese whey was characterized and several
      hydrolysis experiments were made using whey proteins and purified beta
      lactoglobulin, as substrates, and trypsin and alpha-chymotrypsin, as catalysts,
      at two temperatures and several enzyme concentrations. Maximum degrees of
      hydrolysis obtained experimentally were compared to the theoretical values and
      peptide compositions were calculated. For trypsin, 100% of yield was achieved;
      for alpha-chymotrypsin, hydrolysis seemed to be dependent on the oligopeptide
      size. The results showed that the two proteases could hydrolyze beta
      lactoglobulin. Trypsin and alpha-chymotrypsin were stable at 40 degrees C, but a
      sharp decrease in the protease activity was observed at 55 degrees C.

PMID- 11963905
TI  - Solid-state fermentation of phytase from cassava dregs.
AB  - Phytases produced by numerous microorganisms and plants degrade phytic acid that
      has chelated with metal ions in food and feed. It is important to study phytase
      for the role of metal ions in nutrition of animals and humans as well as in the
      reduction of organic phosphate content of aqueous environment. This article
      reports on solid-state fermentation of phytase from a new substrate of cassava
      dregs. Large quantities of cassava dregs are produced in tropical areas as a
      byproduct of cassava starch processing. Protein and inorganic salts were found to
      be low in cassava dregs. Cassava dregs could be employed for phytase synthesis
      after the addition of a nitrogen source and mineral salts. Ammonium nitrate was
      the best nitrogen source among the nitrogen sources investigated, including beef
      extract, yeast extract, urea, ammonium nitrate, sodium nitrate, and ammonium
      sulfate. Sodium dodecyl sulfate promoted phytase production from cassava dregs. A
      maximum phytase yield of 6.73 U/g of dry mass was obtained. The obtained phytase
      was stable at feed-processing temperature, since 70% of initial enzyme activity
      was maintained after 30 min of treatment at 75 degrees C.

PMID- 11963906
TI  - The effect of additional autopolyploidization in a slow growing cellulase
      hyperproducer of Trichoderma.
AB  - M14-2 is a cellulase hyperproducer derived from Trichderma reesei QM 6a, but with
      a growth rate lower than that of the original strain. When M14-2 was
      autopolyploidized followed by haploidization and selection, the strain with both
      a higher cellulase productivity per mycelia and a higher growth rate could be
      obtained as M14-2B. This strain seemed to be constructed using gene sources
      amplified by additional autopolyploidization.

PMID- 11963907
TI  - Effect of pretreatment reagent and hydrogen peroxide on enzymatic hydrolysis of
      oak in percolation process.
AB  - The effect of pretreatment reagent and hydrogen peroxide on enzymatic
      digestibility of oak was investigated to compare pretreatment performance.
      Pretreatment reagents used were ammonia, sulfuric acid, and water. These
      solutions were used without or in combination with hydrogen peroxide in the
      percolation reactor. The reaction was carried out at 170 degrees C for the
      predetermined reaction time. Ammonia treatment showed the highest delignification
      but the lowest digestibility and hemicellulose removal among the three
      treatments. Acid treatment proved to be a very effective method in terms of
      hemicellulose recovery and cellulose digestibility. Hemicellulose recovery was 65
      90% and digestibilities were >90% in the range of 0.01-0.2% acid concentration.
      In both treatments, hydrogen peroxide had some effect on digestibility but
      decomposed soluble sugars produced during pretreatment. Unlike ammonia and acid
      treatments, hydrogen peroxide in water treatment had a certain effect on
      hemicellulose recovery as well as delignification. At 1.6% hydrogen peroxide
      concentration, both hemicellulose recovery and digestibility were about 90%,
      which were almost the same as those of 0.2% sulfuric acid treatment. Also,
      digestibility was investigated as a function of hemicellulose removal or
      delignification. It was found that digestibility was more directly related to
      hemicellulose removal rather than delignification.

PMID- 11963908
TI  - Fingerprinting Trichoderma reesei hydrolases in a commercial cellulase
      preparation.
AB  - Polysaccharide degrading enzymes from commercial T. reesei broth have been
      subjected to "fingerprint" analysis by high-resolution 2-D gel electrophoresis.
      Forty-five spots from 11 x 25 cm Pharmacia gels have been analyzed by LC-MS/MS
      and the resulting peptide sequences were compared to existing databases.
      Understanding the roles and relationships of component enzymes from the T. reesei
      cellulase system acting on complex substrates is key to the development of
      efficient artificial cellulase systems for the conversion of lignocellulosic
      biomass to sugars. These studies suggest follow-on work comparing induced and
      noninduced T. reesei cells at the proteome level, which may elucidate substrate
      specific gene regulation and response.

PMID- 11963910
TI  - Abstracts from the 2nd International Conference on Chromosome 21 and Medical
      Research on Down Syndrome: Part 2. Barcelona, Spain, April 6-7, 2001.

PMID- 11963909
TI  - Abstracts from the 2nd International Conference on Chromosome 21 and Medical
      Research on Down Syndrome: Part 3. Barcelona, Spain, April 6-7, 2001.

PMID- 11963911
TI  - Proceedings of the symposia: Preventing Cardiovascular Disease: Strategies to
      Eliminate Health Disparities and The Relationship of Stress and Hypertension
      Among African Americans. June 15-16, 2001.

PMID- 11963912
TI  - Facial molluscum: treatment with cryotherapy and podophyllotoxin.

PMID- 11963914
TI  - Vista Award recipients. The best team-based construction.

PMID- 11963913
TI  - [Possible malpractice risk].

PMID- 11963915
TI  - Next on the menu. The changing face of hospital food service management.

PMID- 11963917
TI  - Proceedings and abstracts of the annual conference of Engineering and the
      Physical Sciences in Medicine. EPSM 2001.

PMID- 11963916
TI  - New group targets disaster planning.

PMID- 11963919
TI  - HHS announces final regulation establishing first-ever national standards to
      protect patients' personal medical records.

PMID- 11963920
TI  - A unified nomenclature for TATA box binding protein (TBP)-associated factors
      (TAFs) involved in RNA polymerase II transcription.

PMID- 11963921
TI  - Federal funds begin flowing to states for public health improvements.

PMID- 11963923
TI  - Papers presented at the 82nd Annual Meeting of the New England Surgical Society.
      Providence, Rhode Island, USA. September 21-23, 2001.

PMID- 11963922
TI  - Cystic fibrosis-related diabetes: the role of peripheral insulin resistance and
      beta-cell dysfunction.
AB  - AIMS: The goal of this study was to identify the glycaemic status and investigate
      the roles of peripheral insulin resistance (IR) and pancreatic -cell dysfunction
      in the pathogenesis of cystic fibrosis-related diabetes (CFRD) in adult cystic
      fibrosis (CF) patients with no previous history of glycaemic disturbances.
      METHODS: The glucose tolerance status of 68 CF patients was determined using 2-h
      oral glucose tolerance tests (OGTTs). Peripheral IR was measured using the
      homeostasis model assessment for insulin resistance (HOMA-IR) in the CF group and
      46 normal healthy control subjects. Pancreatic -cell function, calculated as the
      ratio between the 30-min increment in plasma insulin and the corresponding 30-min
      post-OGTT plasma glucose concentration, was also measured in a subset of 30 CF
      patients and 16 normal healthy controls. Extended 180-min OGTTs, with frequent
      plasma glucose and insulin sampling, were also undertaken in 24 CF patients and
      eight normal healthy controls to determine glucose-induced insulin response.
      RESULTS: Of the 68 CF patients studied, 41, 18 and nine were found to have
      normal, impaired and diabetic glucose tolerances, respectively. The mean HOMA-IR
      values (mU/mmol) in the CF patients, as a whole, were not significantly different
      compared with the normal healthy controls (CF 2.2 +/- 1.1 vs. control 1.8 +/-
      0.9; NS). Within the CF group, glycaemic status had no impact on HOMA-IR
      (mU/mmol): 2.2 +/- 1.2 (normal glucose tolerance); 2.0 +/- 1.0 (impaired glucose
      tolerance); and 2.3 +/- 1.1 (diabetic glucose tolerance). -cell function
      (mU/mmol) was not only significantly lower in the CF group (CF 1.65 +/- 1.8; P <
      0.001) but also in the CF group with normal glucose tolerance (2.25 +/- 2.10; P <
      0.01) compared with healthy control (4.98 +/- 2.38). Mean plasma glucose
      concentrations were generally higher and mean plasma insulin concentrations lower
      in the CF group as a whole when compared with normal healthy controls. Within the
      CF group, there was a progressive decline in glucose-induced insulin release with
      worsening glycaemic status. CONCLUSIONS: A lack of difference in peripheral IR,
      measured using HOMA-IR, in the CF group and healthy controls or within the CF
      group with differing glycaemic status suggests that IR does not have a
      significant role in the pathogenesis of CFRD. Pancreatic -cell function, already
      subnormal in CF patients with OGTT-defined normal glucose tolerance status,
      deteriorated further with worsening glycaemic status. This suggests that
      insulinopenia plays a prominent role in the pathogenesis of glucose intolerance
      and subsequent development of CFRD.

PMID- 11963924
TI  - [Abdominal pain in a young woman].

PMID- 11963925
TI  - [A physical factor and the process leading to fatal sexual assault].

PMID- 11963926
TI  - Bowties and brainiacs at the AAAS meeting.

PMID- 11963927
TI  - McClintock and marriage.

PMID- 11963929
TI  - [Immediate adverse reactions to donation: frequency and characterization, Blood
      Bank of the Santa Maria Cardiovascular Clinic , Medellin, 1999. Biomedica
      2001;21:224-7].

PMID- 11963928
TI  - Radioimmunotherapy and NHL: nuclear medicine on the oncology team.

PMID- 11963930
TI  - [Homozygous drepanocytosis in Dakar: effect of the hemoglobin F level, and
      sociocultural and economic factors].
AB  - Sickle cell anemia exhibits significant variations in clinical presentation in
      different populations despite the homogeneity of the genetic defect which is
      involved. Genetic modulation of this disease is known but cannot explain alone
      such observations. Our objectives were to determine the effects of Hb F level,
      sociocultural and economic factors on disease severity in Dakar. Sixty homozygous
      sickle cell patients were followed up between october 1996 and April 1998 during
      which period the severity of the disease was assessed and a "severity index" was
      calculated for each patient. The factors which were identified with proved
      benefit were: Hb F > 15%, a high socioeconomic level, a good understanding of the
      disease, at least 4 medical visits per year. These results allow us to identify
      some potential targets to improve preventive and curative care of this disease.

PMID- 11963931
TI  - [Transplantation of cryopreserved carotids in the rabbit: effect of
      cryoprotective agents].
AB  - The cryopreservation of blood vessels has been carried out for some decades with
      variable results. In order to study the behaviour of cryopreserved allografts by
      using new technique of cryopreservation a study on the ultrastructure arterial
      tissue consequences by microscopic techniques has been carried. The graft has
      been harvested from carotid artery of donor rabbit, implanted to a carotid artery
      of a recipient rabbit and extracted at 1, 3 and 5 months after the operation. An
      intimal thickening and a cellular loss in the media have been observed. However,
      good patency has been observed in all cryopreserved allografts. Manifestations of
      rejection are delayed in groups with polyethylene glycol.

PMID- 11963932
TI  - [Oro-dental treatments in the child under general anesthesia (apropos of an
      initial case)].
AB  - Oro-dental treatments under General Anesthesia (G.A.) depend on precise
      indications and the expected results in some cases in Pediatric Dentistry. In
      this report we have an indication case of oro-dental treatment under G.A. That
      clinical case has allowed us to record the difficulties that we face in Dakar in
      order to realize effectively that technics. That case has also allowed us to
      ascertain the necessity to integrate that practice in the training board in
      Pediatric Dentistry. Actually, the clinical indications of oro-dental treatments
      under G.A. are more and more numerous, and in some cases, the dentist
      intervention becomes a necessity. Moreover, the technics of intervention under
      G.A. for some patients is the more indicated technics to reach the expected
      objectives.

PMID- 11963933
TI  - Suggested guidelines for the practice of arthroscopic surgery.

PMID- 11963934
TI  - Azotobacter chroococcum does not contain sodA or its gene product Mn-superoxide
      dismutase.
AB  - Azotobacter chroococcum and Azotobacter vinelandii grown in Burk medium with 1%
      mannitol (BM) or in BM supplemented with 2.2 mg/mL ammonium acetate (BM+N) were
      found to have only iron-containing and CuZn-containing superoxide dismutase.
      Furthermore, genomic DNA from A. chroococcum and A. vinelandii were subjected to
      polymerase chain reaction analysis using sodA- and sodB-specific primers and
      yielded only a sodB product. These results dispute the assertion by Buchanan and
      Lees (Can. J. Microbiol. 26: 441-447, 1980) that A. chroococcum contains Mn
      superoxide dismutase.

PMID- 11963935
TI  - Click on this link, buy two aspirins, and call me in the morning: a critique of
      online medicine financial arrangements.

PMID- 11963936
TI  - The failure of the ADA -- achieving parity with respect to mental and physical
      health care coverage in the private employment realm.

PMID- 11963937
TI  - The constitutionality of DNA sampling on arrest.

PMID- 11963938
TI  - Statistics, not experts.

PMID- 11963939
TI  - Reuser friendly: a review of the regulation of and the product liability
      regarding the reuse of single-use medical devices.

PMID- 11963940
TI  - Embryonic stem cell research: an ethical justification.

PMID- 11963941
TI  - Group psychosocial support in metastatic breast cancer.

PMID- 11963942
TI  - Cranial CT before lumbar puncture in suspected meningitis.

PMID- 11963943
TI  - Cranial CT before lumbar puncture in suspected meningitis.

PMID- 11963944
TI  - Cranial CT before lumbar puncture in suspected meningitis.

PMID- 11963945
TI  - Cranial CT before lumbar puncture in suspected meningitis.

PMID- 11963946
TI  - Mesenteric venous thrombosis.

PMID- 11963947
TI  - Mesenteric venous thrombosis.

PMID- 11963948
TI  - Mesenteric venous thrombosis.

PMID- 11963949
TI  - Can we rely on the alleged constitutional right to informational privacy to
      secure genetic privacy in the courtroom?

PMID- 11963950
TI  - Bioethical objections to DNA databases for law enforcement: questions and
      answers.

PMID- 11963951
TI  - Genetics and toxic torts.

PMID- 11963952
TI  - Legislative and judicial solutions for mental health parity: S. 543, reasonable
      accommodation, and an individualized remedy under Title I of the ADA.

PMID- 11963953
TI  - Collecting debts from the ill and injured: the rhetorical significance, but
      practical irrelevance, of culpability and ability to pay.

PMID- 11963954
TI  - Westside Mothers and Medicaid: will this mean the end of private enforcement of
      federal funding conditions using section 1983?

PMID- 11963957
TI  - Whose team am I on anyway? Musings of a public defender about drug treatment
      court practice.

PMID- 11963956
TI  - Hospital mergers and the threat to women's reproductive health services: applying
      the antitrust laws.

PMID- 11963955
TI  - A magnetostatic-coupling based remote query sensor for environmental monitoring.
AB  - A new type of in situ, remotely monitored magnetism-based sensor is presented
      that is comprised of an array of magnetically soft, magnetostatically-coupled
      ferromagnetic thin-film elements or particles combined with a chemically
      responsive material that swells or shrinks in response to the analyte of
      interest. As the chemically responsive material changes size the distance between
      the ferromagnetic elements changes, altering the inter-element magnetostatic
      coupling. This in turn changes the coercive force of the sensor, the amplitude of
      the voltage spikes detected in nearby pick-up coils upon magnetization reversal
      and the number of higher-order harmonics generated by the flux reversal. Since
      the sensor is monitored through changes in magnetic flux, no physical connections
      such as wires or cables are needed to obtain sensor information, nor is line of
      sight alignment required as with laser telemetry; the sensors can be detected
      from within sealed, opaque or thin metallic enclosures.

PMID- 11963958
TI  - Control of the permeability loss-peak frequency of Ni81Fe19 thin films through
      laser ablation of triangular and square cluster geometries.
AB  - Laser ablation arrays of triangular and square shaped clusters, comprised of 23
      micrometers diam circular holes, are defined upon 100 nm thick Ni81Fe19 films
      used to control the rf permeability spectra. Cluster-to-cluster spacing is varied
      from 200 to 600 micrometers. For each geometry it is found that the loss peak
      frequency and permeability magnitude shift lower, in a step-wise fashion, at a
      cluster-to-cluster spacing between 275 and 300 micrometers. The nonlinear shift
      in the behavior of the permeability spectra correlates with a dramatic increase
      in domain wall density.

PMID- 11963959
TI  - Magnetoelastic sensors in combination with nanometer-scale honeycombed thin film
      ceramic TiO2 for remote query measurement of humidity.
AB  - Ribbonlike magnetoelastic sensors can be considered the magnetic analog of an
      acoustic bell; in response to an externally applied magnetic field impulse the
      sensors emit magnetic flux with a characteristic resonant frequency. The magnetic
      flux can be detected external to the test area using a pick-up coil, enabling
      query remote monitoring of the sensor. The characteristic resonant frequency of a
      magnetoelastic sensor changes in response to mass loads. [L.D. Landau and E. M.
      Lifshitz, Theory of Elasticity, 3rd ed. (Pergamon, New York, 1986). p.
      100].Therefore, remote query chemical sensors can be fabricated by combining the
      magnetoelastic sensors with a mass changing, chemically responsive layer. In this
      work magnetoelastic sensors are coated with humidity-sensitive thin films of
      ceramic, nanodimensionally porous TiO2 to make remote query humidity sensors.

PMID- 11963960
TI  - Laser pyrolysis fabrication of ferromagnetic gamma'-Fe4N and FeC nanoparticles.
AB  - Using the laser pyrolysis method, single phase gamma'-Fe4N nanoparticles were
      prepared by a two step method involving preparation of nanoscale iron oxide and a
      subsequent gas-solid nitridation reaction. Single phase Fe3C and Fe7C3 could be
      prepared by laser pyrolysis from Fe(CO)5 and 3C2H4 directly. Characterization
      techniques such as XRD, TEM and vibrating sample magnetometer were used to
      measure phase structure, particle size and magnetic properties of these nanoscale
      nitride and carbide particles.

PMID- 11963962
TI  - Improving cellular density estimation.

PMID- 11963961
TI  - High frequency, small signal MH loops of ferromagnetic thin films.
AB  - A method is presented for transforming the high frequency bias susceptibility
      measurements of ferromagnetic thin films into the form of a MH loop with,
      depending upon the measurement geometry, the y-axis zero crossing giving a
      measure of the coercive force or anisotropy field. The loops provide a measure of
      the quantitative and qualitative high frequency switching properties of
      ferromagnetic thin films.

PMID- 11963963
TI  - Characterization of primary culture of rainbow trout (Oncorhynchus mykiss) skin
      explants: growth, cell composition, proliferation, and apoptosis.
AB  - A trout (Oncorhynchus mykiss) epidermal skin primary explant system was evaluated
      over 8 d by light and electron microscopy. Three distinct regions of the explant
      outgrowth were identified on the basis of cell composition. The area immediately
      adjacent to the founder tissue contained mainly small migrating cells and mucous
      cells. Of the former. about 20% were mitotic and 6% apoptotic. The middle area
      was characterized by differentiated pavement cells and mucous cells, with fewer
      small migrating cells. Proliferation was approximately 30% and apoptosis 5%. Over
      time, total cell numbers halved as more pavement cells differentiated. The
      growing front contained many mucous and small migrating cells initially, with few
      pavement cells. About 50% of the cells were in the proliferative phase, and 5%
      were apoptotic. Later, there were fewer migrating and mucous cells, with a higher
      number of pavement cells. About 9% of the cells were apoptotic, and 70% of the
      cells were proliferating. As in vivo, pavement cells had apical microridges,
      although they were vacuolated and contained phagocytosed apoptotic bodies. The
      data and observations are based on the numbers of cell cultures prepared from
      separate trout giving the sample size n = 7. As this culture system is
      reproducible and closely approximates the epidermis of trout, it is a powerful
      tool to study the effects of pollutants, parasites, and endocrine factors on fish
      skin, eliminating whole-animal factors and reducing the number of experimental
      animals required.

PMID- 11963964
TI  - A mineralizing rat dental pulp cell subline expressing collagen type I and dentin
      sialoprotein-phosphophoryn transcripts.
AB  - A mineralizing rat dental pulp cell subclone, termed M2H4, was selected from
      single-cell cloning of the rat dental pulp cell line RPC-C2A by screening
      confluent single-cell cultures for their ability to undergo mineralization. To
      induce mineralization, confluent single-cell cultures were treated for 8 d with
      ascorbic acid followed by the addition of inorganic phosphate to a final
      concentration of 4 mM for an additional 3 d. Confluent M2H4 subclones were shown
      by immunofluorescence and electron microscopy to form collagen type I fibrils.
      Furthermore, using reverse transcriptase-polymerase chain reaction, this subclone
      was found to be capable of expressing dentin sialoprotein-phosphophoryn (DSP-PP)
      transcripts, an odontoblast-specific marker. Thus, this newly identified
      mineralizing rat M2H4 subclone possesses odontoblast-like characteristics and can
      serve as an in vitro model for examining the role of DSP and PP in the formation
      of mineralized dentin.

PMID- 11963965
TI  - Trehalose augments osteoprotegerin production in the FHs74Int human intestinal
      epithelial cell line.
AB  - The disaccharide trehalose has been shown to inhibit both bone loss in
      ovariectomized mice and excessive osteoclastogenesis in lipopolysaccharide
      injected mice. However, the mechanism of osteoclastogenesis inhibition by oral
      administration of trehalose is still unclear. We report here for the first time
      that a human intestinal epithelial cell line, FHs74Int, also produces
      osteoprotegerin (OPG) and that trehalose augments OPG production by this cell
      line. Thus, these results suggest that trehalose promotes the production of OPG
      by intestinal epithelial cells, which then acts on bone marrow cells, resulting
      in the suppression of osteoclastogenesis.

PMID- 11963966
TI  - Characterization of subpopulated articular chondrocytes separated by Percoll
      density gradient.
AB  - The aim of this study was to develop a method for fractionation of articular
      chondrocytes from the entire thickness of the tissue. Isolated chondrocytes from
      rabbit articular cartilage fractionated by centrifugation in a discontinuous
      Percoll gradient resulted in four cell fractions with two differing properties.
      The lowest-density fraction consisted mainly of large cells with small nuclei
      proliferated actively, maintained the chondrocytic phenotype, and secreted larger
      amounts of proteoglycan. In contrast, the highest-density fraction consisted of
      small cells with large nuclei proliferated slowly, did not express the
      chondrocytic phenotype, and produced larger amounts of interleukin 1-induced
      nitric oxide. Comparing our results with other previous reports, we find that
      fraction 1 cells are likely originated from the deep layer of the articular
      cartilage, whereas fraction 4 cells are tentatively categorized as chondrocytes
      from the superficial layer of cartilage. Centrifugal fractionation of articular
      chondrocytes via Percoll density gradient permits clear separation of these
      heterogeneous cells into different phenotypic populations and allows
      distinguishing of cells from the different layers of articular cartilage. This
      simple novel method will provide ready separation of articular chondrocytes for
      the investigation of the pathogenesis of articular cartilage.

PMID- 11963967
TI  - Evaluation of extracellular matrix proteins and tissue inhibitor of matrix
      metalloproteinases-2 on bovine inner cell mass outgrowth in vitro.
AB  - Effects of extracellular matrix proteins and tissue inhibitor of matrix
      metalloproteinases-2 (TIMP-2) on bovine inner cell mass (ICM) outgrowth and
      proteinase production in vitro were determined. Inner cell masses were isolated
      immunosurgically from day 7 embryos (day 0 = onset of estrus) and cultured for 96
      h. In experiment 1, cellular outgrowth and gelatinase production were evaluated
      for ICM cultured on collagen IV, fibronectin, or laminin. More (P < 0.05) ICM
      generated cellular outgrowth on fibronectin (71%). compared with collagen IV (0%)
      or laminin (15%). Inner cell mass and outgrowth areas were greatest (P < 0.05) on
      fibronectin after 96 h of culture, compared with laminin. Although the incidence
      of cellular outgrowth on laminin was limited, numbers of cells in outgrowths
      supported by laminin were similar (P > 0.10) to fibronectin except at 72 h of
      culture, where more (P < 0.05) cells were in laminin than in fibronectin
      outgrowths. Gelatinase activity was not detected in conditioned medium. In
      experiment 2, cellular outgrowth and plasminogen activator production by ICM
      cultured on fibronectin in medium containing 0 or 10 microg/ml TIMP-2 were
      evaluated. Inner cell mass and outgrowth areas, and numbers of cells in
      outgrowths were greater (P < 0.05) in 10 compared with 0 microg/ml TIMP-2 at 96 h
      of culture. Mean plasminogen activator activity in conditioned medium from ICM
      cultured in 10 microg/ml TIMP-2 was greater (P < 0.05) compared with 0 microg/ml
      TIMP-2 (16.2 +/- 4.8 versus 6.7 +/- 1.4 x 10(-3) IU/ml, respectively). These
      results demonstrate that cellular outgrowth from bovine ICM is supported by
      fibronectin and is stimulated by TIMP-2.

PMID- 11963969
TI  - Protein phosphatase 2A may participate in hepatocytic differentiation.

PMID- 11963968
TI  - Expression of the nuclear coactivators CBP and p300 in developing craniofacial
      tissue.
AB  - cAMP regulatory element-binding protein (CREB)-binding protein (CBP) and its
      functional homolog, the adenovirus E1A -associated 300-kDa protein (p300) are
      nuclear coactivators and histone acetyltransferases that integrate signals from
      disparate pathways by bridging specific transcription factors to the basal
      transcription apparatus. Their role in patterning and development was suggested
      by studies in mice in which CBP and p300 expression was disrupted and by the
      human Rubinstein-Taybi syndrome, which is associated with mutations of CBP. The
      cAMP signal transduction pathway plays a critical role during development of the
      palate. The linkage between cAMP and expression of specific genes is mediated via
      activation of trans-acting deoxyribonucleic acid-binding proteins such as the
      nuclear CREB. For genes regulated by CBP- or p300-containing transcriptional
      complexes, rates of transcription will depend in part on cellular levels and
      distribution of CBP/p300. We have thus determined the temporal and spatial
      expression of CBP and p300 in murine embryonic palatal tissue. Both CBP and p300
      proteins and messenger ribonucleic acids are expressed in palatal tissue on each
      d of palate development (days 12-14 of gestation), as measured by Western
      blotting and reverse-transcription polymerase chain reaction. Expression of both
      CBP and p300 was greatest on day 12 of gestation, suggesting that these
      transcriptional coactivators are developmentally regulated. Immunohistochemical
      analysis of CBP and p300 expression in the murine embryonic craniofacial region
      revealed a ubiquitous distribution for both proteins. These studies lay the
      groundwork for further investigations into the role of CBP and p300 in cellular
      signaling during craniofacial development.

PMID- 11963970
TI  - Sebaceous epithelial cell differentiation requires cyclic adenosine monophosphate
      generation.
AB  - The cyclic adenosine monophosphate (cAMP) generator choleratoxin is known to
      promote the growth of sebaceous epithelial cells (sebocytes) in monolayer culture
      in classical serum-containing media. Now that sebocytes can be grown in serum
      free medium, we have examined whether choleratoxin or other cAMP generators are
      required for differentiation of rat preputial sebocytes in response to specific
      ligand activators of peroxisome proliferator-activated receptors (PPARs).
      Unexpectedly, choleratoxin reduced sebocyte proliferation. However, sebocyte
      differentiation in response to specific PPARalpha and PPARgamma agonists required
      a cAMP generator such as choleratoxin, and this response was suppressed by a
      protein kinase A inhibitor. In contrast, the stable prostacyclin analog,
      carbaprostacyclin (cPGI2), a PPARalpha,delta agonist that also generates cAMP,
      stimulated differentiation independently of choleratoxin. Furthermore, unlike the
      selective PPARalpha and PPARgamma agonists, cPGI2 stimulated both sebocyte DNA
      synthesis and proliferation. These data are compatible with the evidence that
      prostacyclin has the additional effect of generating cAMP. In addition, we
      addressed the possibility that choleratoxin may act as a surrogate for beta
      adrenergic catecholamines in generating cAMP. In contrast with choleratoxin, both
      alpha- and beta-adrenergic catecholamines stimulated sebocyte growth and
      interfered with the choleratoxin effect on differentiation. These data suggest
      ligand-dependent, complex interactions between cAMP and the other signal
      transduction pathways involved in sebocyte growth and development.

PMID- 11963974
TI  - Comparative insecticidal power of three pyrethroids on netting.
AB  - Adult mosquitoes, Anopheles gambiae Giles and Culex quinquefasciatus Say
      (Diptera: Culicidae), were exposed for 3 min to replicate samples of polyester
      netting cut from replicate bednets treated with pyrethroid insecticide
      formulations at the recommended concentration (alphacypermethrin SC at 40mg
      ai/m2; cyfluthrin EW at 50 mg ai/m2; deltamethrin WT at 25 mg ai/m2), or treated
      with only a quarter of those dosages. After 4 months domestic use of the bednets
      in Malawi, chemical assays showed that pyrethroid deposits on the netting were
      somewhat less than the target concentrations. Comparing the pyrethroid bioassay
      results with Anopheles at both treatment concentrations, deltamethrin gave
      significantly higher mortality (99.7-100%) than the other compounds
      (alphacypermethrin 94-96%, cyfluthrin 80-89%). Culex bioassay mortality was lower
      (alphacypermethrin 56-74%; cyfluthrin 63-65%; deltamethrin 50-81 %) and results
      with the three pyrethroid insecticides at their recommended doses did not differ
      significantly.

PMID- 11963973
TI  - Vector competence of South African Culicoides species for bluetongue virus
      serotype 1 (BTV-1) with special reference to the effect of temperature on the
      rate of virus replication in C. imicola and C. bolitinos.
AB  - The oral susceptibility of 22 South African livestock associated Culicoides
      species to infection with bluetongue virus serotype 1 (BTV-1) and its replication
      rate in C. imicola Kieffer and C. bolitinos Meiswinkel (Diptera: Ceratopogonidae)
      over a range of different incubation periods and temperatures are reported. Field
      collected Culicoides were fed on sheep blood containing 7.5 log10TCID50/mL of BTV
      1, and then held at constant different temperatures. Virus replication was
      measured over time by assaying individual flies in BHK-21 cells using a
      microtitration procedure. Regardless of the incubation temperatures (10, 15, 18,
      23.5 and 30 degrees C) the mean virus titre/midge, infection rates (IR) and the
      proportion of infected females with transmission potential (TP = virus
      titre/midge > or = 3 log10 TCID50) were found to be significantly higher in C.
      bolitinos than in C. imicola. Results from days 4-10 post-infection (dpi), at 15
      30 degrees C, shows that the mean IR and TP values in C. bolitinos ranged from
      36.7 to 87.8%, and from 8.4 to 87.7%, respectively; in C. imicola the respective
      values were 11.0-13.7% and 0-46.8%. In both species the highest IR was recorded
      at 25 degrees C and the highest TP at 30 degrees C. The time required for the
      development of TP in C. bolitinos ranged from 2 dpi at 25 degrees C to 8 dpi at
      15 degrees C. In C. imicola it ranged from 4 dpi at 30 degrees C to 10 dpi at
      23.5 degrees C; no individuals with TP were detected at 15 degrees C. There was
      no evidence of virus replication in flies held at 10 degrees C. When, at various
      points of incubation, individual flies were transferred from 10 degrees C to 23.5
      degrees C and then assayed 4-10 days later, virus was recovered from both
      species. The mean virus titres/midge, and proportion of individuals with TP and
      IR, were again significantly higher in C. bolitinos than in C. imicola. Also the
      infection prevalence in C. magnus Colaco was higher than in C. imicola. Low
      infection prevalences were found in C. bedfordi Ingram & Macfie, C. leucostictus
      Kieffer, C. pycnostictus Ingram & Macfie, C. gulbenkiani Caeiro and C. milnei
      Austen. BTV-1 was not detected in 14 other Culicoides species tested; however,
      some of these were tested in limited numbers. The present study indicates a
      multivector potential for BTV transmission in South Africa. In C. imicola and C.
      bolitinos the replication rates are distinct and are significantly influenced by
      temperature. These findings are discussed in relation to the epidemiology of
      bluetongue in South Africa.

PMID- 11963971
TI  - Human duodenal spheroids for noninvasive intracellular pH measurement and
      quantification of regulation mechanisms under physiological conditions.
AB  - Three-dimensional cell cultures (spheroids) of biopsies of human duodenum were
      used to develop a new noninvasive method for studying intercellular and
      intracellular mechanisms. Through examinations of intracellular pH regulation,
      high functional similarity to native tissue could be shown, as already evidenced
      morphologically. A special microperfusion chamber was developed to fix individual
      spheroids physically to a nylon net, via laminar perfusion flow through the
      chamber. A significant improvement over current fixation methods was shown by the
      increase of cell viability almost up to 100%. Viability of the spheroids was
      confirmed by trypan blue exclusion, by a LIVE/DEAD viability/cytotoxicity kit,
      and by BCECF distribution. Intracellular pH was measured by use of the pH
      sensitive fluorescence dye BCECF. To investigate the intracellular pH regulation,
      spheroid-like vesicles were acidified by NH4Cl prepulse technique. The subsequent
      active intracellular pH recovery was blocked with Na+-free Krebs Henseleit (KH)
      solution, with amiloride KH (inhibitor of the Na+-H+-exchanger), or with H2DIDS
      KH (inhibitor of the HCO3(-)-Cl(-)-exchanger and Na+-HCO3(-)-cotransporter). The
      intracellular pH of the spheroids was 7.31 +/- 0.05. pH-backregulation after
      acidification was prevented by sodium-free buffer, amiloride, and H2DIDS. These
      experiments indicated the presence of a Na+-H+-exchanger and a Na+-HCO3(-)
      cotransporter. In conclusion, the human duodenal spheroid is an excellent
      physiological system for in vitro studies of the human duodenum.

PMID- 11963975
TI  - Male size does not affect mating success (of Anopheles gambiae in Sao Tome).
AB  - For malaria control, the utility of transgenic vector Anopheles mosquitoes
      (Diptera: Culicidae) refractory to Plasmodium transmission, will depend on their
      interbreeding with the wild vector population. In many species, larger males are
      more successful in obtaining mates. In Sao Tome island, we determined that size
      did not affect mating success of male Anopheles gambiae Giles sensu stricto, the
      main malaria vector in tropical Africa. Also we showed that larval intraspecific
      competition is probably insignificant in this population of An. gambiae. Thus,
      the potential success of transgenic An. gambiae is unlikely to be affected by
      size selection under field conditions.

PMID- 11963972
TI  - Factors influencing the abundance of Japanese encephalitis vectors in ricefields
      in India--II. Biotic.
AB  - The relationship of insect predators and phytoplankton with the abundance of
      Culex tritaeniorhynchus Giles, Cx. vishnui Theobald and Cx. pseudovishnui Colless
      mosquito larvae and pupae (Diptera: Culicidae) in ricefields was investigated
      during three rice growing seasons. Notonectids were the most abundant insect
      predators, whereas diatoms dominated among phytoplankton. Multiple regression
      analysis showed that the occurrence of notonectids (both nymphs and adults) was
      negatively associated with larval abundance. Phytoplankton, especially diatoms
      and blue green algae (BGA), were found to favour abundance of culicine immatures
      during Navarai and Kuruvai crops, respectively. Larval gut analysis showed that
      the intake of algae by late instars was high, with 93%, 58% and 24% of diatoms,
      BGA and green algae, respectively. Filamentous algae may not necessarily be of
      nutritive value, but they are observed to form mats, which provide protection to
      the mosquito immatures from the predators.

PMID- 11963976
TI  - Malaria outbreak control in an African village by community application of 'deet'
      mosquito repellent to ankles and feet.
AB  - The malaria vector Anopheles arabiensis Patton (Diptera: Culicidae) shows a
      marked predilection (> 80%) for biting the ankles and feet of human subjects, as
      revealed by our previous observations at Malahlapanga in the Kruger National
      Park, South Africa. Topical application of insect repellent, 15% deet (N,N
      diethyl-3-methylbenzamide), to feet and ankles reduced the overall biting rate of
      An. arabiensis by 69%. A focal malaria epidemic in Albertsnek village (25 degrees
      33'S, 31 degrees 59' E) near the Mozambique border, following flooding during
      February 2000, provided an opportunity to apply these findings of operational
      research for outbreak containment. Twice-nightly topical application of deet to
      ankles and feet of Albertsnek inhabitants was followed by rapid restoration of
      preepidemic malaria incidence levels after one incubation period. This
      encouraging outcome should be attempted in other outbreak-prone settings where
      infective mosquito bites are sporadic and malaria has unstable endemicity.

PMID- 11963977
TI  - Impact of untreated bednets on prevalence of Wuchereria bancrofti transmitted by
      Anopheles farauti in Papua New Guinea.
AB  - Despite the growing evidence that insecticide-treated mosquito nets reduce
      malaria morbidity and mortality in a variety of epidemiological conditions, their
      value against lymphatic filariasis infection and disease is yet to be
      established. The impact of untreated bednets on the prevalence of Wuchereria
      bancrofti (Cobbold) (Nematoda: Filarioidea) infection and disease was
      investigated on Bagabag island in Papua New Guinea, where both malaria and
      filariasis are transmitted by the same vector mosquitoes of the Anopheles
      punctulatus Donitz group (Diptera: Culicidae). Community-wide surveys were
      conducted recording demographic characteristics including bednet usage. Physical
      examinations for hydrocoele and lymphoedema were performed and blood samples
      assessed for filarial and malaria parasites. Mosquitoes were sampled using the
      all-night landing catch method and individually dissected to determine W.
      bancrofti infection and infective rates. Bednet usage among residents was 61% and
      the mean age of users (25.6 years) was similar to non-users (22.5 years).
      Anopheles farauti Laveran was the only species were found to contain filarial
      larvae: 2.7% infected (all stages), 0.5% infective (L3). The overall W. bancrofti
      microfilaraemia and antigenaemia rates were 28.5% and 53.1%, respectively. Bednet
      users had lower prevalence of W. bancrofti microfilaraemia, antigenaemia and
      hydrocoele rates than non-users. In comparison, untreated bednets had no effect
      on the prevalence and intensity of Plasmodium falciparum and P. vivax infections.
      The impact of bednet usage on rates of microfilaraemia and antigenaemia remained
      significant even when confounding factors such as age, location and sex were
      taken into account, suggesting that untreated bednets protect against W.
      bancrofti infection.

PMID- 11963978
TI  - A simple method for calculating mosquito mortality rates, correcting for seasonal
      variations in recruitment.
AB  - A simple age-structured exponential growth model is presented for the analysis of
      the population dynamics of mosquitoes (Diptera: Culicidae). In this model, the
      proportion of parous mosquitoes R depends on the birth rate beta, and the length
      of the first gonotrophic cycle g, but not on the mortality rate. If the age
      structure is fairly constant, R = exp(- betag). Extensions of the model
      correcting for feeding patterns are given. A simple method is applied to an
      example of Anopheles gambiae Giles biting density and parity ratio in Cjte
      d'Ivoire (fortnightly sampled longitudinal data set), for calculation of the
      seasonally fluctuating mortality rate, correcting for effects of recruitment. The
      seasonal variations in birth rate and mortality rate are discussed in relation to
      variations in density and rainfall.

PMID- 11963980
TI  - Methods for the recovery of mitochondrial DNA sequences from museum specimens of
      myiasis-causing flies.
AB  - Mitochondrial DNA (mtDNA) sequences from eight species of myiasis-causing flies,
      stored for up to 50 years, were amplified successfully. Universal primers were
      used to amplify six specific regions from total genomic DNA, including five mtDNA
      genes. The comparison of phenol/chloroform, DNAzol and Chelex techniques for DNA
      extraction showed that the DNAzol reagent was the most efficient in retrieving
      DNA from museum specimens, although the Chelex extraction procedure is currently
      the most frequently reported method. Comparison of the universal primer sequences
      with the homologous sequences of Cochliomyia hominivorax Coquerel and Chrysomya
      putoria Wiedemann (Diptera: Calliphoridae) revealed mismatches that could
      contribute to the low recovery of a short sequence from subunit II of cytochrome
      oxidase. The ability to characterize mtDNA markers from museum specimens should
      be useful in comparative studies of contemporary samples and should help in
      elucidating species introduction, colonization and dispersal.

PMID- 11963979
TI  - Malaria transmission risk variations derived from different agricultural
      practices in an irrigated area of northern Tanzania.
AB  - Malaria vector Anopheles and other mosquitoes (Diptera: Culicidae) were monitored
      for 12 months during 1994-95 in villages of Lower Moshi irrigation area (37
      degrees 20' E, 3 degrees 21' S; approximately 700 m a.s.l.) south of Mount
      Kilimanjaro in northern Tanzania. Adult mosquito populations were sampled
      fortnightly by five methods: human bait collection indoors (18.00-06.00 hours)
      and outdoors (18.00-24.00 hours); from daytime resting-sites indoors and
      outdoors; by CDC light-traps over sleepers. Anopheles densities and rates of
      survival, anthropophily and malaria infection were compared between three
      villages representing different agro-ecosystems: irrigated sugarcane plantation;
      smallholder rice irrigation scheme, and savannah with subsistence crops.
      Respective study villages were Mvuleni (population 2200), Chekereni (population
      3200) and Kisangasangeni (population approximately/= 1000), at least 7 km apart.
      Anopheles arabiensis Patton was found to be the principal malaria vector
      throughout the study area, with An. funestus Giles sensu lato of secondary
      importance in the sugarcane and savannah villages. Irrigated sugarcane
      cultivation resulted in water pooling, but this did not produce more vectors.
      Anopheles arabiensis densities averaged four-fold higher in the ricefield
      village, although their human blood-index was significantly less (48%) than in
      the sugarcane (68%) or savannah (66%) villages, despite similar proportions of
      humans and cows (ratio 1:1.1-1.4) as the main hosts at all sites. Parous rates,
      duration of the gonotrophic cycle and survival rates of An. arabiensis were
      similar in villages of all three agro-ecosystems. The potential risk of malaria,
      based on measurements of vectorial capacity of An. arabiensis and An.funestus
      combined, was four-fold higher in the ricefield village than in the sugarcane or
      savannah villages nearby. However, the more realistic estimate of malaria risk,
      based on entomological inoculation rates, indicated that exposure to infective
      vectors was 61-68% less for people in the ricefield village, due to the much
      lower sporozoite rate in An. arabiensis (ricefield 0.01%, sugarcane 0.1%,
      savannah 0.12%). This contrast was attributed to better socio-economic conditions
      of rice farmers, facilitating relatively more use of antimalarials and bednets
      for their families. Our findings show that, for a combination of reasons, the
      malaria challenge is lower for villagers associated with an irrigated rice
      growing scheme (despite greater malaria vector potential), than for adjacent
      communities with other agro-ecosystems bringing less socio-economic benefits to
      health. This encourages the development of agro-irrigation schemes in African
      savannahs, provided that residents have ready access to antimalaria materials
      (i.e. effective antimalaria drugs and insecticidal bednets) that they may better
      afford for protection against the greater vectorial capacity of An. arabiensis
      from the ricefield agro-ecosystem.

PMID- 11963981
TI  - SCAR markers and multiplex PCR-based identification of isomorphic species in the
      Anopheles dirus complex in Southeast Asia.
AB  - The Anopheles dirus Peyton & Harrison complex of mosquitoes (Diptera: Culicidae)
      comprises seven known species, including important malaria vectors in Southeast
      Asia. Specific identification of each species of the complex, which cannot be
      distinguished using morphological characters, is crucial for understanding vector
      ecology and implementing effective control measures. Derived from individual
      random amplified polymorphic DNA (RAPD) markers, sequence characterized amplified
      regions (SCAR) were analysed for the design of specific paired-primers.
      Combination of six SCAR primers resulted in the development of a simple, robust,
      single multiplex PCR able to identify three important malaria vectors among the
      four most common species (A, B, C, D) of the complex: species A from several
      Southeast Asian countries, species B from Perlis, Malaysia, and species C and D
      from Thailand.

PMID- 11963982
TI  - Participatory investigations of bovine trypanosomiasis in Tana River District,
      Kenya.
AB  - Participatory research on bovine trypanosomiasis was conducted with Orma
      pastoralists in Tana River District, Kenya. The use of participatory methods to
      understand local perceptions of disease signs, disease causes, disease incidence
      by cattle age group, seasonal patterns of disease and preferences for indigenous
      and modern control methods are described. Results indicated that local
      characterization of diseases called gandi and buku by Orma pastoralists was
      similar to modern veterinary knowledge on chronic trypanosomiasis and
      haemorrhagic trypanosomiasis (due to Trypanosoma vivax), respectively. The mean
      incidence of gandi varied from 10.2% in calves to 28.6% in adult cattle. The mean
      incidence of buku varied from 3.1% in calves to 9.6% in adults. Pearson
      correlation coefficients for disease incidence by age group were 0.498 (P < 0.01)
      and 0.396 (P < 0.05) for gandi and buku, respectively. Informants observed cases
      of trypanosomiasis in 24.1% of cattle (all age groups); these cases accounted for
      41.8% of all sick cattle during the preceding 12-month period. Eight indigenous
      and three modern trypanosomiasis control methods were identified. Results
      indicated that an integrated approach to trypanosomiasis control based on
      private, individual action was well established in the assessment area. When
      presented with four different trypanosomiasis control methods, community
      representatives selected 'better use of trypanocides' as the most preferred
      intervention and 'community-based tsetse control' as the least preferred
      intervention. This finding prompted researchers to modify the original project
      activities. Constraints facing the sustainability of community-based tsetse
      control are discussed.

PMID- 11963984
TI  - A new species of Triatominae from Tamil Nadu, India.
AB  - A new species of the genus Linshcosteus Distant, 1904 (Hemiptera: Reduviidae:
      Triatominae) is described from specimens collected near Kalakkadu, Tamil Nadu
      state, southern India. Specimens were found in deep crevices between rocks, in a
      region of semi-arid scrub jungle. The distinctiveness of the new species was
      demonstrated by a morphometric analysis including the five previously described
      species of Linshcosteus, all from India. Nine measurements of the head were used
      in an isometric size-free principal component analysis. In terms of discrete
      morphology the new species, Linshcosteus karupus sp.n. Galvao, Patterson, Rocha &
      Jurberg differs from the most similar one, L. kali Lent & Wygodzinsky, 1979, by
      its very prominent anterolateral projections of the pronotum, by the length to
      width ratio of the pronotum, by the pilosity of the head and several other
      characters, including phallic structures. A revised key is presented for the six
      species of the genus.

PMID- 11963983
TI  - Development of an exposure-free bednet trap for sampling Afrotropical malaria
      vectors.
AB  - An exposure-free bednet trap (the 'Mbita trap') for sampling of Afrotropical
      malaria vectors was developed during preliminary studies of mosquito behaviour
      around human-occupied bednets. Its mosquito sampling efficiency was compared to
      the CDC miniature light-trap and human landing catches under semi-field
      conditions in a screen-walled greenhouse using laboratory-reared Anopheles
      gambiae Giles sensu stricto (Diptera: Culicidae). When compared in a competitive
      manner (side by side), the Mbita trap caught 4.1+/-0.5 times as many mosquitoes
      as the CDC light-trap, hung beside an occupied bednet (P < 0.000 1) and 43.2+/
      10% the number caught by human landing catches (P < 0.0001). The ratio of Mbita
      trap catches to those of the CDC light trap increased with decreasing mosquito
      density. Mosquito density did not affect the ratio of Mbita trap to human-landing
      catches. In a non-competitive comparison (each method independent of the other),
      the Mbita trap caught 89.7+/-10% the number of mosquitoes caught by human landing
      catches (P < 0.0001) and 1.2+/-0.1 times more mosquitoes than the CDC light trap
      (P = 0.0008). Differences in Mbita trap performance relative to the human landing
      catch under noncompetitive vs. competitive conditions were explained by the rate
      at which each method captured mosquitoes. Such bednet traps do not expose people
      to potentially infectious mosquito bites and operate passively all night without
      the need for skilled personnel. This trap is specifically designed to catch host
      seeking mosquitoes only and may be an effective, sensitive, user-friendly and
      economic alternative to existing methods for mosquito surveillance in Africa.

PMID- 11963985
TI  - Allozyme relationships among ten species of Rhodniini, showing paraphyly of
      Rhodnius including Psammolestes.
AB  - Genetic relationships among 10 species of bugs belonging to the tribe Rhodniini
      (Hemiptera: Reduviidae), including some important vectors of Chagas disease, were
      inferred from allozyme analysis of 12 enzyme loci (out of 21 enzyme systems
      examined), using agarose gel electrophoresis. These species formed two clusters:
      one comprising Rhodnius brethesi, R. ecuadoriensis, R. pallescens and R.
      pictipes; the other with Psammolestes tertius, Rhodnius domesticus and the
      Rhodnius prolixus group comprising R. nasutus, R. neglectus, R. prolixus and R.
      robustus. The resulting tree was [((R. ecuadoriensis, R. pallescens) R. brethesi)
      R. pictipes], [R. domesticus (P. tertius [(R. nasutus, R. neglectus) (R.
      prolixus, R. robustus)])]. Rhodnius nasutus and R. neglectus differed by only one
      locus, whereas no diagnostic loci were detected between R. prolixus and R.
      robustus (22 loci were analysed for these four species), despite considerable DNA
      sequence divergence between species in each of these pairs. Allozymes of the R.
      prolixus group showed greater similarity with Psammolestes tertius than with
      other Rhodnius spp., indicating that Rhodnius is paraphyletic and might include
      Psammolestes.

PMID- 11963986
TI  - L-lactic acid: a human-signifying host cue for the anthropophilic mosquito
      Anopheles gambiae.
AB  - Using a dual-choice olfactometer, the role of L-lactic acid was investigated in
      relation to host-seeking and selection by female Anopheles gambiae Giles sensu
      stricto (Diptera: Culicidae) mosquitoes in a Y-tube bioassay. L-lactic acid alone
      was not attractive, but it significantly augmented the attractiveness of CO2,
      skin odour and skin-rubbing extracts from humans and other vertebrates. Comparing
      the left and right index fingers of the same person, one could be made more
      attractive than the other by adding L-lactic acid to the air stream over that
      finger. The difference in L-lactic acid concentration between the two air streams
      offered to the mosquitoes fell within the natural range of variation emanating
      from a human hand, suggesting that L-lactic acid modulates intraspecific host
      selection by An. gambiae. Analysis of skin rubbings from various vertebrates
      (carnivores, chickens, primates, rodents, ungulates) indicated that humans have
      uniquely high levels of L-lactic acid on their skin. Tests with extracts of skin
      rubbings from cows and humans, with and without added L-lactic acid, suggest that
      naturally lower levels of L-lactic acid contribute to the lesser attractiveness
      of non-humans to An. gambiae s.s.

PMID- 11963987
TI  - Structural organization of the estalpha3(1) gene in a Colombian strain of Culex
      quinquefasciatus differs from that in Cuba.
AB  - In Culex mosquitoes (Diptera: Culicidae), the most common mechanism for
      resistance to organophosphorus (OP) insecticides involves amplification of one or
      more esterases. Two esterase loci are often involved, with different allelic
      forms co-amplified. Estalpha3(1) is co-amplified with estbeta1 in a Colombian
      (COL) strain of Culex quinquefasciatus Say. These two alleles co-migrate on
      acrylamide gels, often leading to misscoring of the phenotype as elevation of a
      single estbeta enzyme. By sequencing COL genomic DNA, we determined the
      estalpha3(1) gene length is 1623 nucleotides. The open reading frame of
      estalpha3(1) encodes a 540 amino acid protein, as for estalpha2(1) in strain Pel
      RR from Sri Lanka. The intron/exon boundaries of estalpha3(1) are identical to
      those of estalpha2(1), suggesting that they are alleles of the same locus. The
      COL estalpha3(1) gene differs from estaalpha3(2) in strain MRES from Cuba,
      although they have equivalent electrophoretic mobility, showing that these two
      strains contain distinct resistance-associated amplicons. Twenty nucleotide
      differences were scored between the MRES partial 495 bp sequence and that in the
      COL strain, with two amino acid changes, demonstrating distinct estalpha enzymes.
      Our sequencing data show 95% identity between the three estalpha genes (each has
      six introns and seven exons) in OP-resistant Cx. quinquefasciatus. Amplified
      estalpha3(1) and estbeta1 are at least 10kb apart in temephos-selected COL and
      2.7kb apart in Pel RR, whereas these non-amplified genes are only 1.7kb apart in
      the nonselected parental COL stock, as in Pel SS (susceptible Sri Lankan strain),
      demonstrating that this region of the genome is susceptible to expansion and
      contraction.

PMID- 11963988
TI  - Quantitative estimation of interaction between carbohydrates and concanavalin A
      by surface plasmon resonance biosensor.
AB  - We measured the affinity of more than 20 sugars with concanavalin A (ConA) by an
      optical biosensor (surface plasmon resonance sensor) using asialofetuin (ASF) as
      an immobilized binding partner of ConA. We determined kinetic parameters of the
      effects of sugars on the dissociation of ConA from ASF quantitatively, and the
      structural requirements of the functional groups of sugars for binding with ConA.
      We found that the affinity of ConA for sugars is dependent on its conformation
      induced by interaction with the binding partner. In addition, the results showed
      that optical biosensor system is well mimics the interaction of ConA with sugars
      in biomembrane.

PMID- 11963989
TI  - (4-Methoxy-benzylidene)-(3-methoxy-phenyl)-amine, a nitrogen analog of stilbene
      as a potent inhibitor of melanin production.
AB  - The current study was carried out to investigate in vitro the effects of (4
      methoxy-benzylidene)-(3-methoxyphenyl)-amine on melanin biosynthesis which is
      closely related to hyper-pigmentation. (4-Methoxy-benzylidene)-(3-methoxy-phenyl)
      amine, a nitrogen analog of stilbene, was synthesized by a single step process.
      This compound inhibited the tyrosinase activity, which converts dopa to
      dopachrome in the biosynthetic process of melanin, and showed a UV-blocking
      effect at UV-B band. The compound also exhibited SOD-like activity, which is
      involved in the protection against auto-oxidation and inhibited melanin
      production in melan-a cell line. Our results suggest the possibility that (4
      methoxy-benzylidene)-(3-methoxy-phenyl)-amine might be used as a skin whitening
      agent.

PMID- 11963990
TI  - Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives. II.
      Optimization of the phenylpiperazine moiety of 1-[5-methyl-1-(2-pyrimidinyl)-4
      pyrazolyl]-3-phenylpiperazinyl-1-trans-propenes.
AB  - A series of novel 3-substituted-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1
      trans-propenes in order to improve the in vitro and in vivo activity of our
      prototype 3-[4-(3-chlorophenyl)-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-4
      pyrazolyl]-1-trans-propene (2) were synthesized and evaluated by assays of growth
      inhibition against several tumor cell lines in vitro and antitumor activity
      against some tumor models when dosed both intraperitoneally and orally in vivo.
      Compounds 7a and 7e, the 3,5-difluorophenyl and 3,5-dichlorophenyl analogues of
      2, respectively, showed significantly more potent cytotoxicity than 2 in vitro
      and potent antitumor activities without causing decrease of body temperature
      related to side effects.

PMID- 11963991
TI  - Tandem vicarious nucleophilic substitution of hydrogen/intramolecular Diels-Alder
      reaction of 1,2,4-triazines into functionalized cycloalkenopyridines.
AB  - Synthesis of 2,3- and 3,4-cyclopentenopyridines, 5,6,7,8-tetrahydroquinolines and
      5,6,7,8-tetrahydroisoquinolines from 1,2,4-triazine derivatives is reported.
      Introduction of an alpha-functionalized methyl substituent (e.g. arylsulphonyl,
      sulphonamide, sulphonic acid ester) into position 3- or 6- of triazines by
      vicarious nucleophilic substitution of hydrogen and subsequent alkylation with
      alkyl iodides bearing an acetylenic function in terminal position afforded
      valuable intermediates for intramolecular Diels-Alder reaction with inverse
      electron demand. When heated at higher temperature, these triazine derivatives
      gave the Diels-Alder cycloadducts, which, after spontaneous extrusion of nitrogen
      moiety, led to a variety of functionalized cycloalkenopyridine derivatives.

PMID- 11963992
TI  - Relative population of S-form and F-form conformers of bryonolic acid and its
      derivatives in equilibrium in CdCl3 solutions.
AB  - Relative populations of S-form (D-E rings: boat-boat form) and F-form (D-E rings:
      chair-chair form) conformers, in equilibrium in CDCl3 solutions, of 20
      derivatives (2-21) of bryonolic acid (D:C-friedoolean-8-en-3beta-ol-29-oic acid)
      (1) were calculated from NMR spectral data (J-values and chemical shifts), with
      the aid of molecular mechanic calculation using a MM2/CONFLEX program system. The
      principal deciding factor of the population ratio was found to be whether the
      functionality at C-29 is trigonal or tetrahedral; the S-form: F-form was 0:100
      32:68 for the "trigonal" type and 48:52-100:0 for the "tetrahedral." The
      reliability of the results is discussed.

PMID- 11963993
TI  - Fluorinated vitamin D analogs to probe the conformation of vitamin D in its
      receptor complex: 19F-NMR studies and biological activity.
AB  - To investigate vitamin D conformation, specifically the A-ring and seco-B ring
      parts, in its complex with the vitamin D receptor (VDR), we have previously
      suggested the use of 19F-NMR spectroscopy and have synthesized three
      fluorovitamin D derivatives to be used for the study, 4,4-difluoro-1alpha,25
      dihydroxyvitamin D3 [4,4-F2-1,25-(OH)2D3, 2a], and (10Z)- and (10E)-19-fluoro
      1alpha,25-dihydroxyvitamin D3 [19-F-1,25-(OH)2D3, 3a, 4a]. In this paper, we
      examined the 19F-NMR spectra of these and related fluorovitamin D compounds in
      detail. In the low temperature 19F-NMR spectra, we observed two well-separated
      rigid conformations of 2a (51:49) and 4a (84:16), while only one conformation was
      detected with 3a. The two observed conformers of 2a and 4a were respectively
      assigned to the known alpha- and beta-conformers formed by the flipping of the A
      ring where the C(19) exocyclic methylene points to the alpha- and beta-faces. The
      single conformation observed for 3a was assigned to the alpha-conformer. We
      detected no other conformation in the 19F-NMR of all vitamin D compounds
      examined. The effect of solvents on the 19F chemical shifts of fluorovitamin D
      compounds was found to be small (less than 6.3 ppm). This was much smaller than
      the difference between the two A-ring conformers (13-30 ppm). Using the dynamic
      1H-NMR studies of fluorovitamin D compounds, we determined the free energy of
      activation for the interconversion between the two conformations of 2a (9.9
      kcal/mol) and 4a (10.8, 11.5 kcal/mol). Introduction of the 1alpha-hydroxyl group
      raised the activation energy about 1 kcal/mol. The affinity for VDR was
      evaluated, and the relative potency of 2a, 3a and 4a was found to be 1%, 8% and
      9%, respectively, of that of 1,25-(OH)2D3 (1). Though the affinity for VDR was
      considerably reduced in these compounds, the ability to activate gene
      transcription was similar and remained in the range 30-50% of the effect of 1.
      This biological information in combination with the NMR properties indicates that
      2a and 4a are promising probes for studying the VDR-bound A-ring conformation of
      vitamin D.

PMID- 11963994
TI  - A new synthesis of N-alkyl 3-acetyl-4-methoxycarbonylmethyl-2-methyl-1,4
      dihydropyridines utilizing sec-aminodienyl esters with acetylacetone.
AB  - The reactions of sec-aminodienyl esters 3 with acetylacetone (4) afforded N-alkyl
      3-acetyl-4-methoxycarbonylmethyl-2-methyl-1,4-dihydropyridines 5 and enamines 6,
      providing a new azaelectrocyclization reaction.

PMID- 11963996
TI  - Studies on the constituents of Syringa species. X. Five new iridoid glycosides
      from the leaves of Syringa reticulata (Blume) Hara.
AB  - Five new iridoid glycosides, (8Z)-ligstroside (1), (8Z)-nuzhenide (3), 6'-O-alpha
      D-glucopyranosylsyringopicroside (4), 3'-O-beta-D-glucopyranosylsyringopicroside
      (5) and 4'-O-beta-D-glucopyranosylsyringopicroside (6) were isolated, together
      with a known one, (8E)-nuzhenide (2), from the leaves of Syringa reticulata.
      Their structures were established on the basis of chemical and spectral data.
      Compounds 1 and 3 are the first findings of a (8Z)-oleoside-type secoiridoid.
      Compound 4 is the first naturally occurring iridoid di-glycoside having an
      isomaltose.

PMID- 11963995
TI  - Indonesian medicinal plants. XXIV. Stereochemical structure of perseitol x K+
      complex isolated from the leaves of Scurrula fusca (Loranthaceae).
AB  - A complex of perseitol (D-glycero-D-galacto-heptitol) and K+ ions in a molar
      ratio of 20:1 was isolated from the leaves of Scurrula fusca (Loranthaceae),
      which has been traditionally used for the treatment of cancer in Sulawesi Island,
      Indonesia. The stereochemical structure of the complex in H2O solution has been
      elucidated by use of several kinds of NMR techniques. Furthermore, it has been
      found that the complex exhibits a potent inhibitory effect on [3H]-leucine
      incorporation for protein synthesis in Ehrlich ascites tumor cells in mice.

PMID- 11963997
TI  - Labdane-type diterpenoids from the wood of Cunninghamia konishii.
AB  - Five new labdane-type diterpenes, 12beta,19-dihydroxymanoyl oxide (1), 8(17),13
      labdadien-12,15-olid-19-oic acid (2), 12,15-epoxy-8(17),13-labdadien-18-oic acid
      (3), 8alpha-hydroxy-11E,13Z-labdadien-15-al (4), and (13R)-13-hydroxy-8(17),
      11E,14-labdatrien-18-oic acid (5) were isolated from the wood of Cunninghamia
      konishii. Their structures were elucidated by two-dimensional NMR spectroscopy.

PMID- 11963998
TI  - Water-soluble constituents of dill.
AB  - From the water-soluble portion of the methanol extract of dill (fruit of Anethum
      graveolens L.), which has been used as a spice and medicine, thirty-three
      compounds, including a new monoterpenoid, six new monoterpenoid glycosides, a new
      aromatic compound glucoside and a new alkyl glucoside were obtained. Their
      structures were clarified by spectral investigation.

PMID- 11963999
TI  - New glycosides from the Japanese fern Hymenophyllum barbatum.
AB  - Thirteen glycosides and methyl (3R,5R)-5-hydroxy-(beta-D-glucopyranosyloxy)
      hexanoate were newly isolated from the Japanese fern Hymenophyllum barbatum,
      although our previous work revealed the isolation of hemiterpene glycosides,
      hymenosides A-J, from the same species. The structures of the newly isolated
      glycosides were elucidated by extensive two-dimensional (2D) NMR and/or chemical
      evidence. The structures of those aglycones were divided into four types, 2
      methyl-but-2-ene-1,4-diol, 2-hydroxymethyl-but-2-ene-1,4-diol, 2-methylene-butane
      1,3,4-triol, and 3-hydroxy-5-hexanolide. The sugar moieties, which were acylated
      by phenylacetic acid derivatives, were also established by chemical and
      spectroscopic methods. Eight glucosides of the isolated compounds in the present
      investigation had a bitter or weakly pungent taste. It is clear that a
      phenylacetyl group attached to glucose or allose as an ester is necessary for the
      bitter taste.

PMID- 11964000
TI  - Enzyme inhibitory constituents from Duranta repens.
AB  - Isoprenylated flavonoids 5,7-dihydroxy-3'-(2-hydroxy-3-methyl-3-butenyl)-3,6,4'
      trimethoxyflavone (1), 3,7-dihydroxy-3'-(2-hydroxy-3-methyl-3-butenyl)-5,6,4'
      trimethoxyflavone (2) and an isoprenylated acetophenone derivative (3) have been
      isolated from Duranta repens along with known compounds, 5-hydroxy-3,6,7,4'
      tetramethoxyflavone (4), rosenonolactone (5), 6,7-dimethoxycoumarin (6),
      5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (7) and 5alpha,8alpha
      epidioxyergosta-6,9(11),22-trien-3beta-ol (8), isolated for the first time from
      this species. Their structures and the relative configuration were determined by
      spectroscopic methods (1H- and 13C-NMR, IR, UV and MS) and two-dimensional (2D)
      NMR experiments. The compounds 1-5 showed inhibitory activity against prolyl
      endopeptidase while 4 and 5 were also active against thrombin.

PMID- 11964001
TI  - Aryl-aryl coupling reaction using a novel and highly active palladium reagent
      prepared from Pd(OAc)2, 1,3-bis[diphenylphosphino]propane (DPPP), and Bu3P.
AB  - A palladium-assisted coupling reaction of aryl triflate with arene was
      investigated, and a novel Pd reagent prepared from equimolar Pd(OAc)2, 1,3
      Bis[diphenylphosphino]propane (DPPP), and Bu3P was developed. This method is
      useful for intramolecular biaryl coupling reactions, not only between aryl
      triflate and arene (triflate-amide), but also between aryl halide and arene (halo
      amide).

PMID- 11964002
TI  - Inhibition of cytopathic effect of human immunodeficiency virus type-1 by various
      phorbol derivatives.
AB  - Forty-eight derivatives of phorbol (9) and isophorbol (14) were evaluated for
      their inhibition of human immunodeficiency virus (HIV)-1 induced cytopathic
      effects (CPE) on MT-4 cells, as well as their activation of protein kinase C
      (PKC), as indices of anti-HIV-1 and tumor promoting activities, respectively. Of
      these compounds, the most potent inhibition of CPE was observed in 12-O
      tetradecanoylphorbol 13-acetate (8) and 12-O-acetylphorbol 13-decanoate (6). The
      former also showed the strongest PKC activation activity, while the latter showed
      no activity at 10 ng/ml. Both activities were generally observed in those phorbol
      derivatives with an A/B trans configuration, but not in the isophorbol
      derivatives with an A/B cis configuration. Acetylation of 20-OH in the phorbol
      derivatives significantly reduced the inhibition of CPE, as shown in 12-O-, 20-O
      diacetylphorbol 13-decanoate (6a) (IC100=15.6 microg/ml) vs. compound 6
      (IC100=0.0076 microg/ml), and 12-O-tetradecanoylphorbol 13,20-diacetate (8a)
      (IC100=15.6 microg/ml) vs. 12-O-tetradecanoylphorbol 13-acetate (8)
      (IC100=0.00048 microg/ml), except in the case of 12-O-decanoylphorbol 13-(2
      methylbutyrate) (4) and phorbol 12,13-diacetate (9c). The reduction of a carbonyl
      group at C-3 abruptly reduced the inhibition of CPE, as observed in 3beta
      hydroxyphorbol 12,13,20-triacetate (9f) (IC100=500 microg/ml) vs. phorbol
      12,13,20-triacetate (9d) (IC100=62.5 microg/ml). Although 8 was equipotent in the
      inhibition of CPE, and activation of PKC, both activities were abruptly decreased
      by the acetylation of 20-OH and methylation of 4-OH [as in 8a and 4-O-methyl-12-O
      tetradecanoylphorbol 13,20-diacetate (8b), respectively]. On the other hand, its
      positional isomer (12-O-acetylphorbol 13-tetradecanoate (8c) showed neither
      activities. The removal of a long acyl group in 8 led to a substantial loss of
      both activities, as shown in phorbol 13-acetate (9b). Of the 12-O-acetyl-13-O
      acylphorbol derivatives, the highest inhibition of CPE was observed in 6, which
      has a dodecanoyl residue at C-13. Both an increase and decrease in the number of
      fatty acid carbon chains resulted in significant reduction of the inhibition of
      CPE.

PMID- 11964003
TI  - Practical synthesis of wybutosine, the hypermodified nucleoside of yeast
      phenylalanine transfer ribonucleic acid.
AB  - An improved synthesis of 3-beta-D-ribofuranosylwybutine (2) has been achieved by
      the Wittig reaction between 4,6-dimethyl-9-oxo-3-[2,3,5-tris-O-(tert
      butyldimethylsilyl)-beta-D-ribofuranosyl]-4,9-dihydro-3H-imidazo[1,2-a]-purine-7
      carbaldehyde (8) and the phosphorane derived from (R)-2-[(methoxycarbonyl)amino]
      3-(triphenylphosphonio)propanoate (9), followed successively by methylation,
      hydrogenation, and deprotection. On the other hand, the minor nucleoside
      wybutosine of yeast tRNA(Phe) was isolated on a scale of 80 microg by partial
      digestion of unfractionated tRNA (1 g) with nuclease P1, followed successively by
      reversed-phase column chromatography, complete digestion with nuclease
      P1/alkaline phosphatase, and reversed-phase HPLC. Comparison of this nucleoside
      with 2 has unambiguously established that the structure of wybutosine is (alphaS)
      alpha-[(methoxycarbonyl)-amino]-4,6-dimethyl-9-oxo-3-beta-D-ribofuranosyl-4,9
      dihydro-3H-imidazo[1,2-a]purine-7-butanoic acid methyl ester (2).

PMID- 11964004
TI  - Studies on the constituents of seeds of Pachyrrhizus erosus and their anti herpes
      simplex virus (HSV) activities.
AB  - Studies on the chemical constituents of the seeds of Pachyrrhizus erosus
      (Leguminosae) resulted in the isolation of nine known components: five rotenoids
      [dolineone (3), pachyrrhizone (5), 12a-hydroxydolineone (7), 12a
      hydroxypachyrrhizone (9), and 12a-hydroxyrotenone (2)], two isoflavonoids
      [neotenone (4) and dehydroneotenone (8)], one phenylfuranocoumarin [pachyrrhizine
      (6)], and a monosaccharide (dulcitol). The full 1H- and 13C-NMR assignments for
      the isolated products except a sugar, including revision of previous assignments
      in the literature, are reported. Moderate anti herpes simplex virus (HSV)
      activity was observed in 12a-hydroxydolineone (7) and 12a-hydroxypachyrrhizone
      (9) among the isolated products.

PMID- 11964006
TI  - Lignans and sesquiterpenes from Magnolia praecocissima.
AB  - A new lignan 1 was isolated together with the five known lignans 2-6 and four
      sesquiterpenes 7-10 from the seeds of Magnolia praecocissima. The structure of 1
      was elucidated by analysis of spectroscopic data and chemical reaction.
      Furthermore, the absolute configurations of 1, 2, and 3 were determined by the
      modified Mosher's method.

PMID- 11964005
TI  - Cytotoxic dammarane glycosides from processed ginseng.
AB  - Steaming ginseng at high temperature increased its cytotoxicity to SK-Hep-1
      hepatoma cancer cells. HPLC separation and fractionation followed by MTT assay
      revealed that ginsenosides Rg3, Rg5, Rk1, Rs5, and Rs4 are the active principles.
      Their 50% growth inhibition concentration (GI50) values were 41, 11, 13, 37, and
      13 microM, respectively. Cisplatin had a GI50 of 84 microM in the same assay
      conditions.

PMID- 11964007
TI  - Four new podocarpane-type trinorditerpenes from the bark of Taiwania
      cryptomerioides.
AB  - Further studies on the bark of Taiwania cryptomerioides found four new
      podocarpane derivatives, 1beta,13-dihydroxy-8,11,13-podocarpatriene (1), 14,18
      dihydroxy-13-methoxy-8,11,13-podocarpatriene (2), 1beta,14-dihydroxy-13-methoxy
      8,11,13-podocarpatriene-2,7-dione (3), and 3beta,14-dihydroxy-13-methoxy-8,11,13
      podocarpatrien-7-one (4), together with a known 1beta,13,14-trihydroxy-8,11,13
      podocarpatrien-7-one (5). Those structures were elucidated principally from
      spectral evidence.

PMID- 11964008
TI  - Structure of wyosine, the condensed tricyclic nucleoside of torula yeast
      phenylalanine transfer ribonucleic acid.
AB  - Large-scale isolation of the minor nucleoside wyosine of torula yeast tRNA(Phe)
      was accomplished by a combination of enzymatic digestion and reversed-phase
      chromatography: the wyosine-containing nucleotide fraction, which was obtained by
      partial digestion of unfractionated tRNA (1 g) with nuclease P1, was concentrated
      by reversed-phase column chromatography followed by complete digestion with
      nuclease P1/alkaline phosphatase. The nucleoside mixture thus obtained was
      purified by reversed-phase HPLC, providing wyosine (70 microg). Comparison of
      this nucleoside with a chemically synthesized authentic sample has unambiguously
      established that the structure of wyosine is 4,6-dimethyl-3-beta-D-ribofuranosyl
      3,4-dihydro-9H-imidazo[1,2-a]purin-9-one (2).

PMID- 11964009
TI  - A racemization test in peptide synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2
      yl)-4-methylmorpholinium chloride (DMT-MM).
AB  - Racemization of the C-terminal amino acid (Ala) has been studied in various
      solvents during coupling between 4-methoxybenzyloxycarbonyl (Z(OMe))-Gly-L-Ala-OH
      and phenylalanine benzyl ester (H-Phe-OBzl) with 4-(4,6-dimethoxy-1,3,5-thiazin-2
      yl)-4-methylmorpholinium chloride (DMT-MM). The reaction occurred without
      substantial racemization in AcOEt, tetrahydrofuran (THF), N,N-dimethylformamide
      (DMF), CH3CN, and 2-PrOH, while a slight racemization was observed in dimethyl
      sulfoxide (DMSO), EtOH, and MeOH. The extent of racemization may correlate with
      the polarity of the solvents.

PMID- 11964010
TI  - New sterols from two edible mushrooms, Pleurotus eryngii and Panellus serotinus.
AB  - Two edible mushrooms, Pleurotus eryngii and Panellus serotinus, have been
      investigated chemically. Two new sterols, 5alpha,9alpha-epidioxy-8alpha,14alpha
      epoxy-(22E)-ergosta-6,22-dien-3beta-ol (1) and 3beta,5alpha-dihydroxyergost-7-en
      6-one (2), have been isolated from P. eryngii, together with six known ones (3
      8). Compound 1 was also isolated from P. serotinus. The structures of the new
      compounds were elucidated on the basis of their spectral data.

PMID- 11964011
TI  - Cycloserine fatty acid derivatives as prodrugs: synthesis, degradation and in
      vitro skin permeability.
AB  - Various 4,5-dihydroisoxazol-3-yl fatty acid ester derivatives of cycloserine were
      synthesized to improve skin permeation of cycloserine. The ester derivatives were
      prepared by using the tert-butoxycarbonyl (t-Boc) protection strategy. The 4,5
      dihydroisoxazol-3-yl esters were readily hydrolysed in an aqueous buffer
      solution, and the degradation profiles showed both specific acid and specific
      base catalysis. In 50% human serum the formation of cycloserine was observed, but
      enzymatic catalysis was limited. Delivery through hairless mouse skin was
      investigated, and the apparent permeability coefficient was measured based on the
      flux of cycloserine into the receptor phase. The skin permeation of cycloserine
      across the hairless mouse skin was increased up to 20-fold by the fatty acid
      esters. The 4,5-dihydroisoxazol-3-yl fatty acid esters of cycloserine can
      therefore be considered as new topical prodrugs with the potential use in
      treatment of various skin infections.

PMID- 11964012
TI  - Synthesis of new chiral sulfinyldiacetic acid derivatives and attempt at
      chemoselective asymmetric Pummerer reaction.
AB  - (R(S))-1 (85% ee) was prepared by utilizing a porcin pancreatic lipase-promoted
      hydrolysis of sulfinyldiacetic acid dimethyl ester (8) which was derived from
      thiodiacetic acid (7). (R(S))-1 (99% ee) and (S(S))-1 (99% ee) were readily
      obtained by methanolysis of (R(S),S)-12 and (S(S),S)-12 with MeONa in MeOH.
      (R(S),S)-12 and (S(S),S)-12 were furnished by chromatographic separation of the
      diastereomeric mixture, obtained by oxidation of thiodiacetic mono-carboxylic
      acid (11) with 30% H2O2 followed by dehydrative condensation of the resultant
      sulfinyldiacetic mono-carboxylic acid with 4(S)-isopropyl-1,3-thiazolidine-2
      thione. (R(S))-1 (99% ee) was successively treated with (TMS)2NLi, Ac2O, and
      TMSOTf to give a major chiral-3 product in 75% ee and in a highly chemoselective
      manner (chiral-3:chiral-2=93:7).

PMID- 11964013
TI  - Remarkably enhanced inhibitory effects of three-component hybrid liposomes
      including sugar surfactants on the growth of lung carcinoma cells.
AB  - Sugar parts play important roles in recognizing molecules on the cell membranes.
      We successfully produced sugar-type micellar surfactants, lactonoalkylamide
      (LacCn), for the first time. Spherical vesicles, three-component hybrid
      liposomes, were obtained after the sonication of the mixture of L-alpha
      dimyristoyl-phosphatidylcholine (DMPC), Tween 20 and LacCn (DMPC:Tween
      20:LacCn=65:7:28). It is noteworthy that high inhibitory effects of the three
      component hybrid liposomes composed of DMPC, Tween 20, and LacCn (DMPC:Tween
      20:LacCn=65:7:28) on the growth of glioma (U251) and lung adenocarcinoma (RERF-LC
      OK) cells were attained in vitro without any drug, although no significant
      inhibitory effects of any individual component (DMPC, Tween 20, LacCn) or the two
      component hybrid liposomes of DMPC and Tween 20 on the growth of tumor cells
      examined were obtained.

PMID- 11964014
TI  - Physiology and possible pathology of growth hormone secretagogues.
AB  - Growth hormone segretagogues (GHS) are artificial molecules able to stimulate
      growth hormone (GH) secretion. They were discovered before the hypothalamic
      growth hormone-releasing hormone (GHRH). These molecules had a structure devoid
      of opiate activity, and GHRP-6 is the most representative compound. These
      compounds identified a new physiological system involved in GH regulation, and
      their action is independent of GHRH or somatostatin. Recently an endogenous
      ligand for the GHS receptor, ghrelin, was discovered, suggesting that this may be
      the third factor in the control of GH secretion. This peptide was isolated from
      the stomach and is characterized by the presence of an acylated group
      representing a new type of molecular hormonal structure; it is able to stimulate
      GH secretion in vitro and in vivo in the rat. As observed for the majority of
      GHS, ghrelin's action is not fully specific for GH release; the acute
      administration of ghrelin stimulates the release of significant amounts of PRL,
      ACTH and cortisol. Moreover, the presence of ghrelin in rat and human placenta
      has been reported, suggesting a possible role of this peptide in the local
      modulation of GH release and in maternal and fetal pituitary secretion. Ghrelin
      stimulates gastric acid secretion, is able to induce adiposity by activating a
      central mechanism for increasing food intake and decreasing fat utilization, and
      ghrelin mRNA and peptide are expressed in normal and adenomatous human pituitary
      tissue. Possible therapeutic applications of ghrelin remain to be assessed.

PMID- 11964015
TI  - Genetic aspects of pituitary tumors.
AB  - Pituitary adenomas arise from the replication of a single mutated cell in which
      growth advantage may result from either activation of protooncogenes or
      inactivation of antioncogenes. The search for oncogenes in the genesis of these
      tumors has yielded negative results except for the gsp oncogene, that has been
      identified in about 30-40% of GH-secreting adenomas. gsp mutations cause
      constitutive activation of the Gs alpha subunit, leading to elevated cAMP
      formation and growth hormone hypersecretion. In the remaining tumor types several
      lines of evidence suggest that genes implicated in cell proliferation, such as
      early immediate genes, growth factors and growth factor receptors, are
      overexpressed. As far as the loss of antioncogenes in pituitary adenomas is
      concerned, no inactivating mutations of these genes have yet been identified in
      pituitary adenomas. However, despite the lack of mutations, several antioncogene
      proteins have been detected at extremely low levels in pituitary adenomas,
      consistent with a possible role of these tumor suppressors in pituitary tumor
      formation.

PMID- 11964016
TI  - Non-secreting pituitary tumors in adolescents--consequences in adulthood.
AB  - This article reviews non-secreting pituitary tumors in children and adolescents.
      These tumors include a wide range of pathological situations. They differ from
      those in adults regarding incidence, pathology, clinical presentation, size and
      consequences. Pituitary tumors are uncommon in this age group (2.7% of
      intracranial tumors) whilst in adults they represent 22.5-27%. Pituitary adenomas
      are the most frequent in adults (30%) while craniopharyngiomas are more common in
      children and adolescents (80-90%). Of pituitary adenomas in children and
      adolescents, non-secreting pituitary adenomas are very rare (3-6%) and are
      usually macroadenomas. These are usually benign, not life threatening, but can
      profoundly affect the quality and length of life because of serious secondary
      complications. In spite of the difficulties presented, surgery is the treatment
      of choice for most of these tumors. Even following the best of treatment,
      however, there is a great possibility of permanent pituitary insufficiency. In a
      large percentage of patients, these adverse effects of the tumors can be
      prevented by early and rapid intervention and treatment.

PMID- 11964017
TI  - Prolactinomas in children and adolescents--consequences in adult life.
AB  - Prolactinomas in children and adolescents are rare. However, they represent,
      together with corticotropinomas, the most frequent types of pituitary tumors in
      adolescence. Most prolactin-secreting pituitary tumors are microprolactinomas but
      many, and particularly those in men, are macroadenomas. The clinical findings
      that would usually project into the adult life of patients, in other words the
      issue of transitory endocrinology from childhood to adulthood, are menstrual
      irregularities, infertility, short stature, osteopenia and/or osteoporosis, and
      sometimes psychometric abnormalities. The therapy of choice for both macro- and
      microprolactinomas is one of the new dopamine agonists, such as quinagolide or
      cabergoline. Recent evidence-based data have clearly promoted cabergoline as the
      first-line treatment. Cabergoline may normalize prolactin secretion, restore
      fertility in women and men. and induce tumor shrinkage. Today, transsphenoidal
      surgery should be considered only in patients with a large extrasellar extension.

PMID- 11964018
TI  - Growth hormone deficiency in the transition adolescent: should treatment be
      continued in adult life?
AB  - Adults with growth hormone (GH) deficiency (GHD) have impaired health, which
      improves with GH replacement. GHD in adulthood leads to impairment in body
      composition and structure functions as well as to deranged lipoprotein and
      carbohydrate metabolism leading to increased cardiovascular morbidity. Therefore
      the transition adolescent in whom severe GHD is confirmed has to continue GH
      replacement with an appropriate age-related dosage. All short children who have
      been treated with rhGH for classical and non-classical GHD should be suspected as
      potentially GHD in adulthood though only in classical organic and idiopathic
      forms is severe GHD likely to be confirmed. GHD must be shown biochemically by
      single provocative testing. Insulin-induced hypoglycemia (ITT) and GHRH +
      arginine are the tests of choice provided that appropriate cutoff limits are
      assumed; these tests show good specificity and sensitivity. Testing with GHRH +
      GH secretagogues is another reliable alternative. Low IGF-I levels can be
      definitive evidence of persistent severe GHD in patients with genetic GHD or
      panhypopituitarism, but normal IGF-I levels do not rule out severe GHD.
      Individual titration of the rhGH dose is recommended and measurement of IGF-I
      levels is needed for monitoring the adequacy of replacement. The mean GH dose for
      replacement in the transition adolescent, however, is still higher than in
      adulthood; after puberty the rhGH dose should be progressively decreased in the
      following years (probably up to 25 years old) in order to obtain optimal peak
      bone mass.

PMID- 11964019
TI  - Consequences of not treating children with laron syndrome (primary growth hormone
      insensitivity).
AB  - The follow-up of a large cohort of patients with Laron syndrome (LS) from infancy
      to adult age has enabled us to determine the effects of long-term insulin-like
      growth factor-I (IGF-I) deficiency on auxological, biochemical, physiological and
      psychological parameters. We found that early and continuous IGF-I deficiency
      (the anabolic effector of growth hormone) causes dwarfism, acromicria,
      organomicria, marked obesity, insulin resistance, retardation of skeletal
      maturation and osteoporosis, as well as muscular and central nervous tissue
      underdevelopment, and a series of biochemical changes including
      hypercholesterolemia. These multiple pathologies impair the quality of life of
      these patients. It is concluded that patients with LS need IGF-I replacement
      treatment throughout life.

PMID- 11964020
TI  - Quality of life and retrospective perception of the effect of growth hormone
      treatment in adult patients with childhood growth hormone deficiency.
AB  - Divergent findings on the quality of life (QoL) and the psychosocial functioning
      of adults treated during childhood with growth hormone (GH) because of GH
      deficiency (GHD) have been reported. In the present study we evaluated the QoL
      and the perception of the effect of former GH treatment in Belgian young adults
      with childhood GHD. Thirty-six patients (22 males) were included in the study.
      They all were treated during childhood with GH for GHD. QoL was evaluated with a
      standardised questionnaire: the Quality of Life Assessment of Growth Hormone
      Deficiency in Adults (QoL-AGHDA). Psychosocial functioning, sexual experience and
      schooling were evaluated by semi-structured interviews and questionnaires. The
      influence of gender, type of hormone deficiency (isolated GHD vs multiple
      pituitary hormone deficiencies [MPHD]), age at the start of GH therapy (before 12
      yr vs after 12 yr) and the height deficit at the start of GH therapy (< -3 SDS vs
      > -3 SDS) were studied. In addition, the patients' and parents' perception of
      height and of the effect of GH treatment was retrospectively evaluated by semi
      structured interviews. Age (mean +/- SD) at the time of evaluation was 20.0 +/-
      1.3 yr and final height was -0.5 +/- 0.9 SDS, comparable to mid-parental height (
      0.6 +/- 0.8 SDS). The QoL-AGHDA score was 9 +/- 6. About half of the patients,
      especially those in whom GH treatment was started after the age of 12 years,
      complained of retrospective difficulties with self-confidence and social contact,
      and about one-quarter of the patients had current difficulties with self
      confidence, social contact, contact with the opposite sex and with emotional
      life. Only 44% of the patients had had sexual intercourse--none of those with
      MPHD. According to the parents, the patients had and still have more difficulties
      with self-confidence and social contact than their siblings and/or peers, and
      they needed and still need more emotional support. In one out of four patients
      the parents expected difficulties in finding a job, in one out of three patients
      parents expected difficulties in leaving home or in having a stable relationship.
      The educational level of patients with a height deficit < -3 SDS at start of GH
      therapy was lower than in patients with a height deficit > -3 SDS. According to
      the parents, about half of the patients, especially those with MPHD, had more
      study problems compared to siblings. In all patients, satisfaction with final
      height and GH therapy was obvious. In conclusion, the psychosocial outcome of
      young adults with childhood GHD was more satisfying than in previous studies.
      This could be due to a more adequate GH treatment with better final height
      results. Nevertheless, more difficulties with respect to psychosocial functioning
      were observed in patients with MPHD, in patients in whom GH treatment was started
      after 12 years of age and in patients with a height deficit < -3 SDS at the start
      of GH therapy, underlining the need for early diagnosis and treatment of
      childhood GHD, and of continuing medical follow-up and psychosocial counselling,
      particularly in these subgroups of patients with GHD.

PMID- 11964021
TI  - Central hypothyroidism: consequences in adult life.
AB  - Central hypothyroidism (CH) is a rare cause of hypothyroidism, generally due to
      either pituitary or hypothalamic defects. On the basis of its etiology, it is
      possible to distinguish acquired and hereditary forms. Hereditary CH can be
      isolated or associated with combined pituitary hormone deficiency (CPHD). In the
      former case, alterations of only two genes, TSHbeta and the TRH receptor, have so
      far been described as responsible for the disorder. In hereditary CH associated
      with CPHD, inactivating mutations of different pituitary transcription factors
      (HESX1, PROP-1, POU1F1) have been found involved in the pathogenesis of the
      disease. Finally, an association between CH and severe obesity has been described
      in patients with leptin receptor (Leptin-R) mutations. The clinical consequences
      of CH in adult life vary greatly depending on the etiology, the severity of the
      thyroid impairment, the extent of the associated hormone deficiencies, and the
      age of the patient at the time of the onset of the disease. In general, acquired
      CH is less severe than the congenital form because of the constitutive activity
      of the wild-type TSH-receptor. Symptoms and signs of thyroid insufficiency are
      usually milder than those of primary hypothyroidism, and goiter is always absent.
      In CPHD, most patients have other endocrine manifestations of the disease (growth
      failure, delayed puberty, adrenal insufficiency, diabetes insipidus) that lead
      them to seek medical attention before the hypothyroidism becomes severe. Early
      diagnosis of the congenital form by neonatal screening for hypothyroidism is
      strongly recommended in order to avoid cretinism. Replacement therapy with L
      thyroxine administration has to be established as soon as possible.

PMID- 11964022
TI  - Clustering of autoimmune thyroid diseases in children and adolescents: a study of
      66 families.
AB  - Autoimmune thyroid diseases (AITD) are known to be clustered in families, but to
      what extent this occurs in childhood and adolescence is not well defined. In
      order to establish the prevalence of AITD in the siblings of affected children
      and adolescents, we examined 73 siblings from 66 families selected on the basis
      of a pediatric index patient. Sixty-six families, including a total of 146
      offspring, were selected on the basis of diagnosis of chronic lymphocytic
      thyroiditis (CLT) (n = 55) or Graves' disease (GD) (n = 11). Among the 73
      siblings examined, 20 new cases of CLT (27%) were detected. L-Thyroxine therapy
      was required in 4/20. History of AITD was recorded in 24/66 mothers (36%), and in
      two fathers. Overall in these families, considering both the index patients and
      the new patients, 86/141 (61%) children and adolescents were affected with AITD,
      with a female/male ratio of 3.3:1. Our study confirms that AITD clusters in
      families with a high prevalence in the siblings of affected children and
      adolescents. These children should be followed in order to avoid undiagnosed
      hypothyroidism. Prospective studies are warranted to identify predictive factors
      for overt thyroid disease.

PMID- 11964023
TI  - The aftermath of childhood hyperthyroidism.
AB  - Long-term consequences of juvenile hyperthyroidism can result both from the
      disease itself and from the treatment used. In most children with thyrotoxicosis,
      the manifestations of the disease on bone metabolism, cardiac function and
      neurological and psychiatric findings are related to the hyperthyroid status and
      disappear with restoration to the euthyroid state. Late late consequences are
      unknown. Permanent adverse effects are due to the treatments used. Antithyroid
      drugs are associated with mild adverse consequences in 28% of the patients
      treated. Serious complications, such as agranulocytosis, aplastic anemia and
      death, have been reported. Review of surgical complications showed the incidence
      of permanent hypoparathyroidism 2%, permanent cord paralysis 2% and approximately
      one death for each 1,000 thyroidectomies. The adverse effects of radioiodine
      therapy remain largely theoretical, when children were treated with ablative
      doses of I131. Childhood ophthalmopathy improves after radioiodine therapy.

PMID- 11964024
TI  - Thyroid nodules in children and adolescents: consequences in adult life.
AB  - Thyroid nodules are very common in the general population, but less so in
      children. If present, however, in children or adolescents, the likelihood of
      malignancy is increased. The endocrinologist must look for an etiological factor,
      such as iodine deficiency, previous irradiation, infections or autoimmunity,
      assess thyroid function, and especially exclude malignancy. For this, fine-needle
      aspiration biopsy (FNAB) is the most important procedure. If malignancy is
      suspected, thyroidectomy is advised, otherwise thyroxine treatment or follow-up.
      Whether operated or not, the patient needs life-long follow-up, with or without
      thyroxine treatment. Especially for young persons, such follow-up is unpleasant,
      hence the need for the physician to support his patients psychologically.

PMID- 11964025
TI  - Thyroid cancer in children and adolescents--consequences in later life.
AB  - Thyroid cancer is rare below the age of 16 years, with an annual incidence of
      0.02-0.3 cases per 100,000. Papillary and follicular thyroid cancer in childhood
      and adolescence is more advanced upon presentation than in adults, as evident
      from a higher frequency of extra-thyroidal spread. The recurrence rate is also
      higher. Nevertheless, the prognosis for survival in children and adolescents is
      better than in adults; why this is so remains unclear. An approximately 30-fold
      increase in the incidence of thyroid cancer has been observed in children exposed
      to the fallout of the Chernobyl accident, especially in the age group of <1 year
      at the time of the disaster. Medullary thyroid cancer in childhood and
      adolescence occurs mainly as part of the MEN2 syndrome. Early detection by DNA
      mutation analysis and treatment by prophylactic thyroidectomy results in a
      potential normal life expectancy. Consequences in adult life relate to long-term
      complications of thyroid surgery, 131I treatment and TSH-suppressive doses of L
      T4.

PMID- 11964026
TI  - Prenatal diagnosis and treatment of congenital adrenal hyperplasia and
      consequences in adults.
AB  - Prenatal diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
      deficiency is possible using chorionic villus and amniotic fluid cells for DNA
      analysis of the CYP21B gene and the C4 and HLA class I and II genes. Mutations
      can be identified on 95% of the chromosomes using Southern blot analysis and
      selective amplification of the CYP21B gene by polymerase chain reaction followed
      by allele-specific hybridization with oligonucleotide probes for a panel of nine
      known CYP21B mutations. Prenatal treatment with dexamethasone at doses between
      0.5 and 2 mg/day is successful in three-quarters of the treated cases in
      eliminating or reducing the masculinization of the affected female external
      genitalia. The mother must be closely monitored for any adverse effects to her
      health such as hypertension or glucose intolerance. Prenatal dexamethasone
      treatment does not seem to have an adverse effect on growth, psychological
      development, or school performance except for increased shyness, internalizing
      and decreased social behavior. Animal studies, however, have shown abnormalities
      in the fetal brain and behavior of the animals. Prenatal dexamethasone treatment
      is still offered with caution to the parents of a potentially affected CAH
      female.

PMID- 11964027
TI  - Genetic aspects of congenital adrenal hyperplasia.
AB  - Data related to genetics of congenital adrenal hyperplasia with emphasis on CYP21
      gene defects are briefly outlined. Mutations of the StAR gene lead to impaired
      translocation of cholesterol from the outer mitochondrial membrane to the inner
      mitochondria, a rate limiting step in steroidogenesis in the adrenals and the
      gonads. The clinical picture is characterized by adrenal and gonadal
      insufficiency and sex reversal in XY individuals. Molecular defects of the CYP17
      gene encoding 17alpha-hydroxylase can cause hypertension, impaired sexual
      maturation and impaired sexual differentiation in XY individuals. Molecular
      defects of the CYP11B1 gene lead to 11-hydroxylase deficiency, which is
      clinically expressed with virilization of the external genitalia of the female
      and precocious puberty in the male, as well as hypertension in both sexes. The
      HSD3beta1 and HSD3beta2 genes encode two isoenzymes (3betaHSDI and 3betaHSDII).
      The clinical picture results from either absence or diminished activity of type
      II 3betaHSD, resulting from mutations of the HSD3beta2 gene. The most frequent
      form of CAH (90% of all patients) is due to deletions, conversions or point
      mutations of the CYP21 gene, which encodes the enzyme 21-hydroxylase. There is a
      wide range of clinical expression primarily explained by the type of the
      molecular defect. The ratio of genotype to phenotype concordance varies in the
      different forms of the disease, the highest one being encountered in the non
      classical form. Heterozygosity of CYP21 mutations may be expressed as premature
      pubarche.

PMID- 11964028
TI  - Hirsutism of adrenal origin in adolescents: consequences in adults.
AB  - Hirsutism is a common clinical and psychological problem in women. Polycystic
      ovary syndrome and idiopathic hirsutism are the most common causes of hirsutism.
      Adrenal disorders are less common causes of hirsutism; the most common adrenal
      cause of hirsutism is non-classical congenital adrenal hyperplasia (NC-CAH).
      Hirsutism may be the presenting symptom of an adrenal carcinoma or adenoma. In
      this review, adrenal causes of hirsutism, the pathophysiology of the hirsutism in
      NC-CAH, and the treatment of hirsutism in these patients, are discussed.

PMID- 11964029
TI  - Prevalence and trends in overweight and obesity among children and adolescents in
      Thessaloniki, Greece.
AB  - Obesity is the most prevalent nutrition-related problem in Western societies.
      Childhood obesity is rapidly emerging as a global epidemic that will have
      profound public health consequences, as overweight children become overweight
      adults. The aim of this study was to investigate the prevalence of overweight and
      obesity among children and adolescents in the city of Thessaloniki, and evaluate
      the trends in Greece by comparing our results to those of other cross-sectional
      studies. Data concerning the height and weight of 2,458 schoolchildren aged 6 to
      17 years (1,226 6-10 years, 1,232 11-17 years) of 27 primary and secondary public
      schools were collected. BMI was calculated from the two measurements. In the
      analyses, the estimations of the prevalence of overweight and obesity are based
      on recently established international BMI percentile curves and cut-off points
      from 2-18 years. To investigate the secular trends in obesity in Greece, data of
      schoolchildren from four successive surveys were used. In the younger group (6-10
      yr), the prevalence of overweight and obesity were 25.3% and 5.6%, while for
      adolescents (11-17 yr) they were 19.0% and 2.6%, respectively. The prevalence was
      25.9% and 5.1% for all males, and 19.1% and 3.2% for all females, respectively.
      As far as trends are concerned, an increase of BMI was found among males when the
      results of our survey were compared with those of the previous three. However,
      the trends for girls are different. An increase was found when the results of our
      study were compared with 1942. A decrease of BMI at most ages was found when the
      results of our study were compared with those of the 1982 survey, while an
      increase was recorded only for younger girls below 13 years compared to the 1984
      5 study. This study demonstrates that the prevalence of overweight and obesity
      among schoolchildren is 22.2% and 4.1%, respectively, and has been increasing in
      the last decades, especially among boys.

PMID- 11964030
TI  - Determinants of body mass index in Greek children and adolescents.
AB  - The aim of this study was to investigate the determinants of body mass index
      (BMI) among Greek children and adolescents, such as parental age and BMI, number
      of family members in the household, parents' educational status and occupation,
      physical activity and hours of television viewing and playing computer games by
      children per day. This cross-sectional study included 2,495 children aged 6-17
      years from primary and high schools of Thessaloniki, capital of Northern Greece.
      Data were collected by questionnaires concerning age, height and weight of the
      parents, number of family members, and socioeconomic status as determined by
      occupation and educational status of the parents. Our results revealed that
      overweight in Greek children and adolescents is influenced positively by several
      determinant factors, such as parental age and obesity, hours of television
      viewing, and negatively by a high parental educational level. No significant
      association was found between children's BMI and physical activity. Intervention
      and prevention measures should be targeted at the reduction of sedentary
      activities, especially television viewing, and promotion of physical activity.
      These measures should be directed at families that are affected and/or concerned
      with obesity.

PMID- 11964031
TI  - Childhood onset of obesity: does an obese child become an obese adult?
AB  - The aim of this study was to highlight the influence of age of obesity onset on
      anthropometric parameters in obese adults. We examined 1,451 obese adults with
      childhood or adolescent onset of obesity, divided into three subgroups in regard
      to age of onset of obesity: group A--onset before 4 years, group B--onset between
      5 and 11 years, and group C--onset between 12 and 19 years. Significantly higher
      values for body mass index (BMI) and waist circumference (WC) were found in
      groups with earlier obesity onset, but not for body fat percent (%BF) and waist
      to hip ratio (WHR). Age of obesity onset may have a significant influence in the
      persistence of obesity and adverse consequences in adult life. Treatment of
      obesity and other risk factors for cardiovascular diseases should be initiated as
      early as possible.

PMID- 11964032
TI  - Effects of childhood and adolescent obesity on morbidity in adult life.
AB  - In order to determine the influence of onset of obesity on blood lipid levels and
      blood pressure (BP) in Serbian obese adults, we examined 500 obese adults: 250
      with childhood or adolescent onset of obesity (prior to age 19)--Group A; 250
      with adult onset of obesity (after age 19)--Group B. The following variables were
      assessed: anthropometric measurements, lipid profiles and BP. In Group A we found
      higher plasma triglycerides (p <0.01), lower HDL-cholesterol levels (p <0.01) and
      higher values of indices of atherogenic risk: LDL-C/HDL-C (p <0.05), TC/HDL-C (p
      <0.05) and Al (p <0.05). Group A had significantly higher values of systolic (p
      <0.05) and diastolic (p <0.05) BP. Our findings suggest that early onset of
      obesity is predictive for the development of dyslipidemia and hypertension in
      adult life and indicate that effective prevention and therapy of obesity in
      childhood and adolescence is important.

PMID- 11964033
TI  - Obesity in children and adolescents--a new epidemic? Consequences in adult life.
AB  - Obesity is one of the most common health problems among children and adolescents,
      with documented increases in prevalence. The highest rates of obesity are
      observed in the United States and eastern and southern European countries. The
      increasing trend of obesity among children could be the result of environmental
      and cultural changes related to physical inactivity in modern society.
      Persistence of obesity from childhood or adolescence into adulthood has been
      consistently demonstrated in all populations in which it has been studied.
      Childhood and adolescent obesity have a significant impact on later mortality and
      morbidity in adulthood. Many of the metabolic and cardiovascular complications
      and some forms of cancer associated with adult obesity have their onset in
      childhood, and understanding of the relationships between childhood and
      adolescent obesity and obesity in adulthood is of value in efforts to try to
      introduce adequate measures for its treatment and prevention.

PMID- 11964034
TI  - Cardiovascular risk in adolescent and young adult obese females with polycystic
      ovary syndrome (PCOS).
AB  - Women with polycystic ovary syndrome (PCOS) could have associated risk for
      cardiovascular disease. The aim of the present study was to investigate the
      relationship between age and metabolic factors on cardiovascular risk in obese
      women with PCOS. Obese patients with PCOS were divided into an adolescent group
      (n=11; age 16.90 +/- 0.45 yr; BMI 35.04 +/- 1.70 kg/m2), and an adult group
      (n=18; age 29.66 +/- 1.31; BMI 34.57 +/- 1.46). We determined basal values of
      glucose, insulin, lipid and fibrinolytic parameters from blood samples taken in
      all patients and matched controls. Significantly different concentrations between
      the groups with PCOS were obtained for glucose, total cholesterol, triglycerides,
      LDL-cholesterol and Apo-B. Elevated concentrations of insulin (20.63 mU/l), both
      insulin sensitivity indexes--G:I ratio (7.52 mg/10(-4) U) and HOMA model (4.11
      mmol/l x U/l(2))--and PAI-1 (5.49 U/ml) were obtained in the adolescent group
      with PCOS compared to controls, with further increase in the adult group with
      PCOS. It seems that the youngest obese population with PCOS represents a cohort
      with potential cardiovascular disease in adulthood.

PMID- 11964035
TI  - Influence of fetal body weight on metabolic complications in adult life: review
      of the evidence.
AB  - Numerous mainly cross-sectional studies have unequivocally shown an inverse
      relationship between birth weight of infants born at term and the incidence of
      impaired glucose tolerance, type 2 diabetes mellitus, insulin resistance,
      hypertension and coronary heart disease. These findings apply to both sexes and
      are not modified by confounding factors such as age or body mass index. Although
      the original studies in the UK involved a relatively small number of subjects
      whose records of birth weight were traced back more than 50 years earlier,
      similar findings were recorded from larger prospective studies in the USA and
      Northern Europe. Studies in twins did not support the theory that genetic factors
      predispose both to low birth weight and morbidity from impaired glucose
      tolerance, insulin resistance or coronary heart disease, and current evidence
      points to a resetting of major hormonal axes that control growth and metabolic
      processes as a possible cause of this association.

PMID- 11964036
TI  - Diabetic nephropathy in children and adolescents and its consequences in adults.
AB  - Insulin dependent diabetes mellitus (IDDM) is a disease predominantly affecting
      children and young adults. Over the last few decades, there has been an increase
      in the number of patients with IDDM which has almost doubled the incidence per
      generation. Evidence suggests that autoimmunity plays an important role in its
      pathogenesis. Diabetic nephropathy is a serious complication of IDDM, affecting
      about one-third of patients. It is accompanied by generalized micro- and
      macroangiopathy, neuropathy and arterial hypertension. Diabetic nephropathy is
      characterized by a long evolution, starting from microalbuminuria and, over 10-20
      years, leading to end stage renal failure (ESRD). Microalbuminuria in children is
      reversible and by no means necessitates evolution to ESRD. Conversely, overt
      albuminuria inevitably progresses to ESRD irrespective of any known treatment.
      The principal pathogenic factors of diabetic nephropathy are glucose metabolic
      derangement and genetic predisposition, but to date no definite candidate gene(s)
      have been established as predisposing to the disease. Once diabetic nephropathy
      is established, it carries a high risk of morbidity and mortality because of the
      concurrent occurrence of other functional abnormalities, some of them life
      threatening. Hemodialysis, peritoneal dialysis and renal transplantation are
      effective treatments of ESRD due to diabetic nephropathy, but recurrence of the
      disease in the renal transplant is very common among patients with IDDM unless
      renal transplantation is accompanied bypancreatic transplantation.

PMID- 11964037
TI  - Autonomic neuropathy in children and adolescents with diabetes mellitus.
AB  - Diabetic autonomic neuropathy (DAN) is a complication that is clinically evident
      in adult patients with diabetes mellitus (DM). Characteristic neuronal
      alterations occur early in the course of the disease. The diagnosis of
      subclinical DAN has been achieved using tests on heart rate variation (HRV) and
      pupillary function. In children, the prevalence of abnormality in three or more
      conventional HR tests ranges from 0.5-10%, the prevalence of reduced HRV using
      power spectral analysis is reported to be 15%, while the prevalence of pupillary
      abnormality ranges from 7.9-19%, in different studies. Pupillary tests have been
      considered more sensitive and reproducible than HR tests. Pupillary abnormalities
      have shown a relationship with duration of DM and glycemic control, while this
      has not been observed in HR variables. From the pupillometry studies it is
      evident that parasympathetic abnormalities precede the sympathetic ones in
      children, as in adults, with DM. It seems that the best tests for the routine
      evaluation of autonomic function in children and adolescents with DM are HR
      response to deep breathing and standing, power spectral analysis of HRV and
      pupillary adaptation in darkness. It is important to identify the children and
      adolescents with impaired indices of autonomic neuropathy in order to take
      appropriate measures to prevent the progression of DAN.

PMID- 11964038
TI  - Endocrinology 2000-2100: some thoughts on our future.

PMID- 11964039
TI  - Pathology, diagnosis and pathogenesis of AA amyloidosis.
AB  - Amyloid is defined as a proteinaceous tissue deposit that shows a typical green
      birefringence in polarised light after staining with Congo red, the presence of
      non-branching linear fibrils of indefinite length with an approximate diameter of
      10-12 nm and a distinct X-ray diffraction pattern consistent with Pauling's model
      of a cross-beta fibril. Approximately 45% of generalised amyloidoses are
      secondary or reactive (AA) amyloidosis. Among the causes of AA amyloidosis are
      rheumatic diseases, idiopathic diseases, inherited diseases, infectious diseases
      and malignant tumours. Recent decades have provided significant advances in our
      understanding of the pathology and pathogenesis of AA amyloidosis. Its
      pathogenesis is multifactorial involving many variables such as primary structure
      of the precursor protein, acute phase response, the presence of non-fibril
      proteins (e.g. amyloid P component, apolipoprotein E, glycosaminoglycans,
      proteoglycans and basement membrane proteins), receptors, lipid metabolism and
      proteases. Study of the pathogenesis of AA amyloidosis has provided many insights
      into the nature of conformational diseases, which may help in the understanding
      of other members of this particularly heterogeneous group of diseases, such as
      Alzheimer's disease and transmissible spongiform encephalopathies.

PMID- 11964040
TI  - Expression of E-cadherin in chordomas: diagnostic marker and possible role of
      tumor cell affinity.
AB  - Chordoma is a relatively rare malignant bone tumor thought to arise from the
      remnants of the fetal notochord. Chordomas express epithelial cell markers such
      as cytokeratin and epithelial membrane antigen (EMA), which strongly suggests
      that the tumor cells grow via the mechanism of epithelial characterized cell-cell
      interactions. However, there are no known reports that have studied epithelial
      characterized cell-adhesion molecules such as E-cadherin or epithelial cell
      adhesion molecule (Ep-CAM) in chordomas. An immunohistochemical investigation was
      performed in seven cases of chordoma to determine the expression of pan
      cytokeratin, Ep-CAM, and E-cadherin. Histological specimens showed the typical
      appearance of conventional chordoma but for two cases of chondroid chordoma.
      Cytokeratin was constantly expressed in conventional chordomas, but it was
      detected among a few cells with physaliphorous appearance in chondroid chordoma
      cases. Although no Ep-CAM expression was noted, E-cadherin was detected in most
      chordoma cells irrespective of histological subtypes. The expression of E
      cadherin was negative among chondrosarcoma cells in this study as previously
      reported, and thus constant E-cadherin expression of chordoma cells suggests a
      role as a useful diagnostic marker to distinguish chondroid chordoma from
      chondrosarcoma. Furthermore, we speculate that E-cadherin may play a role in
      tumor cell adhesion and is also involved with histological and clinical features
      in chordomas.

PMID- 11964041
TI  - CD34+ fibrocytes in neoplastic and inflammatory pancreatic lesions.
AB  - Besides its function as a matrix-producing cell, the CD34+ fibrocyte has been
      reported to be an antigen-presenting cell capable of priming naive T cells in
      situ. Therefore, it has been claimed that the CD34+ fibrocyte may play an
      important role in host response to tissue damage. The objective of the present
      study was to analyze the presence and distribution of CD34+ fibrocytes and smooth
      muscle actin (SMA) reactive myofibroblasts in relation to the underlying
      pancreatic disease. We investigated a total of 12 pancreatic adenocarcinomas, 7
      endocrine tumors of the pancreas, and 8 cases of chronic pancreatitis; in 11
      cases, normal pancreatic tissue was available. The stroma of normal pancreatic
      tissue harbored diffusely scattered CD34+ fibrocytes. Chronic pancreatitis was
      characterized by an increased number of stromal CD34+ fibrocytes paralleled by a
      gain of SMA reactive myofibroblasts which were not observed in the normal
      pancreatic stroma. The stroma of pancreatic ductal adenocarcinomas and endocrine
      tumors was devoid of CD34+ fibrocytes or showed at least a focal loss of this
      cell type, whereas SMA reactive myofibroblasts were detected in both endocrine
      tumors and adenocarcinomas. We conclude that detection of CD34+ fibrocytes may
      constitute an adjunctive tool in distinguishing chronic pancreatitis from ductal
      adenocarcinoma since the absence of this cell population strongly favors a
      neoplastic process. Moreover, CD34+ fibrocytes and myofibroblasts appear to be
      involved in stromal remodeling associated with chronic pancreatitis and ductal
      adenocarcinoma.

PMID- 11964042
TI  - Lobular intraepithelial neoplasia: previously unexplored aspects assessed in 775
      cases and their clinical implications.
AB  - Lobular intraepithelial neoplasia (LIN) is currently considered a risk factor for
      the development of invasive breast cancer of varying morphologies (ductal or
      lobular) and prognoses in either breast. The reason for the high frequency (50%)
      of subsequent development of invasive ductal cancers remains unclear and the
      issue unexplored. A total of 775 LIN cases were retrieved from the Armed Forces
      Institute of Pathology files and separated into three groups using our three
      tiered grading system. The presence or absence of simultaneous invasive cancer
      (ductal or lobular type) and various grades of ductal intraepithelial neoplasia
      (DIN) were noted for each case and correlated with the grade of LIN. Of the 775
      cases, 80% qualified as LIN 2, with the other 20% being relatively evenly split
      between LIN 1 and LIN 3. Of the 775 cases, 163 cases were pure LIN, while
      invasive carcinoma was present in 140 cases. The remaining 472 cases were
      associated with various grades of DIN. The frequency of associated invasive
      carcinomas (ductal and lobular) increased from 14% in LIN 1 to 23% in LIN 3.
      Remarkably, while the frequency of invasive lobular carcinoma increased
      dramatically from 11% in LIN 1 to 86% in LIN 3, the frequency of invasive ductal
      carcinoma markedly decreased with advancing grade of LIN from 89% in LIN 1 to 14%
      in LIN 3. Among the cases of LIN unassociated with invasive carcinoma, DIN was
      present in 75% of LIN 1, 75% of LIN 2, and 66% of LIN 3 cases. The grade of DIN
      was directly proportional to the grade of LIN. Based on the higher frequency of
      invasive lobular carcinoma associated with LIN 3, biopsies with LIN 3 should be
      evaluated diligently for the presence of an associated invasive lobular
      carcinoma. Furthermore, an excisional biopsy should be performed when LIN 3 is
      observed in a core biopsy. The high frequency of DIN associated with LIN might
      suggest that the subsequent invasive ductal carcinomas originate from the
      associated DIN and that some of this may represent a different phenotype of the
      same cells that form the LIN lesion. It is also possible that the neoplastic
      cells may reflect or retain stem cell characteristics with plasticity and the
      capacity to attain or progress into either a ductal or lobular invasive
      phenotype.

PMID- 11964043
TI  - Expression of the adhesion molecule CEACAM1 (CD66a, BGP, C-CAM) in breast cancer
      is associated with the expression of the tumor-suppressor genes Rb, Rb2, and p27.
AB  - The adhesion molecule CEACAM1 (CD66a, BGP, C-CAM) is not only involved in
      maintaining normal tissue architecture, but also acts as a tumor suppressor in
      several experimental systems where loss of CEACAM1 expression results in enhanced
      tumor-cell growth and tumorigenicity. In order to further analyze the role of
      CEACAM1 in the development of breast cancer, we performed Western-blot analysis
      and immunohistochemistry with highly specific monoclonal antibodies in a cohort
      of 68 mammary carcinomas which had also been analyzed for expression of cell
      cycle regulatory proteins cyclin D1, cyclin E, p16, p21, p27, Rb, and Rb2, as
      well as for steroid hormone receptor status, Ki67, and HER2/neu immunoreactivity.
      High CEACAM1 protein expression as found using both methods correlated
      significantly with expression of the retinoblastoma proteins Rb (P=0.004 and
      0.013) and Rb2/p130 (P=0.003 and 0.007). In addition, we found a weak association
      of CEACAM1 expression with p27 protein levels (P=0.087 and 0.039), but with none
      of the other analyzed parameters. These results indicate the possibility of a
      functional link between cell-adhesion molecules and cell-cycle regulation that
      might play an important role in the development of mammary carcinomas.

PMID- 11964044
TI  - Alterations of E-cadherin, alpha-catenin and beta-catenin expression in
      neuroendocrine tumors of the gastrointestinal tract.
AB  - Neuroendocrine tumors (NETs) of the gastrointestinal tract comprise a
      heterogeneous group of neoplasms arising from the diffuse neuroendocrine system.
      These tumors strongly differ from each other on the basis of different
      pathogenetic, clinical, functional, histological, and prognostic patterns.
      Previous studies have shown that abnormal and reduced expression of the E
      cadherin/catenin complex in several human cancers is associated with tumor
      dedifferentiation, advanced clinical stages, and poor survival rate. We assessed
      correlations between the expression of E-cadherin and catenins, Ki-67, and the
      following clinicopathological factors: age, embryological site of origin, size,
      histological growth pattern, the depth of penetration into the intestinal wall,
      and the presence of metastasis. In this study, reduction of membranous E-cadherin
      expression to a variable degree was detected in more than two-thirds (42 of 51)
      of gastrointestinal NETs (19 foregut, 8 midgut, and 24 hindgut) belonging to the
      complete neuroendocrine neoplastic spectrum [18 well-differentiated NETs, 22 well
      differentiated neuroendocrine carcinomas (NECs), and 11 poorly differentiated
      NECs]. The reduction of E-cadherin expression was concomitant with the reduction
      of alpha-catenin (44 of 51) and beta-catenin (35 of 51) expression. Our
      immunohistochemical analysis demonstrated significant differences of percentage
      of membranous positive cells of E-cadherin, alpha-catenin, or beta-catenin
      between normal tissues and well-differentiated NETs (P=0.0038, P=0.004, and
      P=0.0329, respectively), well-differentiated NECs (P<0.001, P<0.001, and P<0.001,
      respectively) and poorly differentiated NECs (P=0.0002, P<0.0002, and P=0.0002,
      respectively). Among the gastrointestinal NETs, there were significantly more
      positive cells of E-cadherin, alpha-catenin, or beta-catenin in well
      differentiated NETs than well-differentiated NECs (P=0.0006, P=0.0065, and
      P=0.0001, respectively) or poorly differentiated NECs (P=0.0053, P=0.0041, and
      P<0.001, respectively). MIB-1 labeling index generally showed a low proliferative
      activity in well-differentiated NETs (0.49+/-0.37) and well-differentiated NECs
      (0.662+/-0.66). A high proliferation rate was observed in poorly differentiated
      NECs (41.518+/-16.59). MIB-1 labeling index was significantly higher in poorly
      differentiated NECs than well-differentiated NETs and well-differentiated NECs
      (P<0.0001 and P<0.0001, respectively). E-cadherin, alpha-catenin, and beta
      catenin expression were correlated significantly with transmural tumor invasion
      (P<0.0001, P=0.0001, and P<0.0001, respectively) and with size (P=0.0013,
      P=0.0001, and P<0.0001, respectively). These results indicate that the alteration
      in the E-cadherin/catenin expression may be involved in the growth and
      progression of gastrointestinal NETs.

PMID- 11964045
TI  - Dpc4 is expressed in virtually all primary and metastatic pancreatic endocrine
      carcinomas.
AB  - DPC4/Smad4 is inactivated in about 50% of pancreatic ductal cancers. It has been
      recently reported that this gene is also inactivated in neoplasms arising from
      pancreatic islet cells, a phenomenon suggested to be related to similar
      progressions of malignancy found in common ductal cancers. To evaluate this
      possibility, we analysed 20 metastases of pancreatic endocrine carcinomas and
      their corresponding primary lesion for inactivation of DPC4 using
      immunohistochemical staining. In fact, immunohistochemical labelling has been
      shown to correlate with DPC4 gene status with high sensitivity and specificity.
      The cancers included 18 nonfunctioning tumours, one gastrinoma and one ViPoma all
      with liver, nodal and/or adrenal metastases. Seventeen were well-differentiated
      and three poorly differentiated endocrine carcinomas. Dpc4 expression was absent
      in only one primary well-differentiated endocrine cancer and its liver
      metastasis, while all the remaining 19 primary tumours and their metastases
      stained positive for the protein. All positively staining cases showed diffuse
      cytoplasmic and nuclear staining in virtually all neoplastic cells. Our data
      suggest that DPC4 is only rarely involved in pancreatic endocrine tumourigenesis
      and give further weight to the hypothesis that tumours arising from pancreatic
      exocrine and endocrine epithelia are genetically distinct.

PMID- 11964047
TI  - Presence of occult cytomegalovirus infection in the brain after orthotopic liver
      transplantation. An autopsy study of 83 cases.
AB  - Cytomegalovirus (CMV) infection remains a highly prevalent systemic complication
      following orthotopic liver transplantation (LT), accounting for a significant
      increase in morbidity and affiliated costs. However, unlike other
      immunosuppressed groups of population, CMV infection of the central nervous
      system in LT is rarely diagnosed, either clinically or postmortem. Furthermore,
      in 20% of the LT patients who develop preterminal neurological complications, the
      etiology remains undetermined. With the hypothesis that at least some of these
      cases could be related to an occult CMV infection, we examined brain tissue from
      83 unselected autopsies of LT patients by morphological, immunohistochemical
      (IHC), in situ hybridization (ISH), and nested polymerase chain reaction (nested
      PCR) techniques. Microglial nodules were observed in 17 brains of the LT group
      (20.4%) but in none of the 36 controls. Isolated positive cells by either IHC,
      ISH, or both techniques, were identified in 11 LT patients (13.2%) and in 2
      controls (5.5%). CMV DNA amplification was obtained from paraffin-embedded
      tissues in 41 of 81 LT cases (50.6%), and in 5 controls (13.8%) (P=0.00017).
      Viral inclusion bodies, inflammatory infiltrates, or necrotizing changes were not
      identified in any case. Our findings indicate an increased susceptibility of the
      brain of LT patients to occult infection by CMV and suggest that a latent or low
      grade infection of the central nervous system could operate as a reservoir of the
      CMV and play a role in some of the unexplained neurological symptoms that appear
      in the postoperative period.

PMID- 11964046
TI  - Analysis of genetic and epigenetic alterations of the PTEN gene in gastric
      cancer.
AB  - The PTEN tumor suppressor gene on 10q23.3, responsible for the Cowden and
      Bannayan-Zonana syndromes, encodes a dual-specificity phosphatase able to
      dephosphorylate both tyrosine phosphate and serine/threonine phosphate residues.
      Mutational inactivation of PTEN has been reported in various malignancies,
      including endometrial cancers, ovarian cancers, and glioblastomas. In this study,
      we investigated PTEN gene mutations in 10 gastric cancer cell lines and 58
      primary gastric cancers by polymerase chain reaction single strand conformation
      polymorphism (PCR-SSCP). Hypermethylation of promoter region CpG islands, an
      alternative mechanism of gene inactivation to coding region mutations, was also
      evaluated by methylation specific PCR (MSP). Only one (1.7%) of the 58 primary
      tumors carried a somatic 5-bp deletion in intron 7 of PTEN, which did not alter
      the mRNA sequence, and no mutations were detected in any of the cell lines.
      Similar levels of PTEN mRNA expression were observed in all cell lines and
      primary tumors studied by RT-PCR, and PTEN promoter CpG islands remained
      unmethylated. Therefore, we conclude that PTEN does not participate in gastric
      carcinogenesis as a tumor suppressor gene.

PMID- 11964048
TI  - Expression of adhesion molecules in allergic lung diseases.
AB  - Endothelial adherence and migration of leukocytes into tissue is mediated by
      different sets of adhesion molecules. The expression of these sets might not only
      preselect the types of leukocytes that enter the inflammatory sites, but also
      activate these leukocytes, induce adherence to epithelial cells, and cause the
      release of cytokines. Atopic asthma, extrinsic allergic alveolitis, and
      sarcoidosis as examples of immunologic lung diseases were investigated for the
      expression of adhesion molecules. Bronchial biopsies in chronic obstructive lung
      disease (COPD) and resected lung tissue of juvenile emphysema were chosen for
      controls. Immunohistochemistry was done on sections from bronchial and
      transbronchial biopsies and on smears from bronchoalveolar lavage cells. In all
      three types of immune disorders, lymphocytes expressed the integrins alpha4/beta1
      (VLA4) and ICAM3, whereas lymphocytes in COPD bronchitis and in emphysema
      controls were unreactive. Eosinophils in atopic asthma bronchitis in contrast to
      COPD bronchitis also expressed both VLA4 and ICAM3. The expression of VCAM1 on
      endothelial cells was only seen in atopic asthma and was related to disease
      activity. The expression of other adhesion molecules was nonspecific. Expression
      of VCAM1 on endothelial cells and its ligand VLA4 on lymphocytes and eosinophils
      seems to be a specific event in atopic asthma. Expression of VLA4 and ICAM3 on
      lymphocytes, however, might be a specific event in all three immune reactions.

PMID- 11964049
TI  - Lectin binding patterns of alveolar epithelium and subepithelial seromucous
      glands of the bronchi in sepsis and controls--an approach to characterize the non
      specific immunological response of the human lung to sepsis.
AB  - A delayed or deficient immunological protection as well as an overstimulation of
      the mucosal immune system may act as possible additional promoters of sepsis
      induced lung injury in patients suffering from a severe septic condition. Lectin
      binding patterns in pulmonary tissue samples obtained at autopsy from septic
      patients and control individuals were studied using 11 carbohydrate-specific
      lectins (Con A, UEA, GSA I, GSA II, MPA, PNA, Jac, WGA, MAA, LPA, and SNA). There
      were no differences in the secretory product of serous parts of bronchial glands
      detectable in the two study groups, whereas lectin binding patterns of alveolar
      epithelium and mucous parts of subepithelial seromucous glands were different in
      sepsis cases when compared to controls. Apart from differences in binding sites
      for alpha-mannose, N-acetyl-neuraminic acid and alpha-(2-6)-galactose (as
      detected by different expression for Con A, MAA and SNA) in the two study groups,
      the main finding was that no binding sites for alpha-N-acetyl-galactosamine (as
      investigated by MPA immunoreactivity) could be detected on alveolar epithelial
      cells and mucous parts of subepithelial seromucous glands in sepsis cases in
      contrast to the presence of such binding sites in the control cases. We
      hypothesize that the finding of an altered secretory product of alveolar
      epithelial cells and bronchial glands in sepsis may be a result of specific
      carbohydrate deprivation or consumption, respectively, possibly due to direct
      bacterial effects or pathogenetic events in response to bacterial toxins during
      the complex cascade of the host's systemic inflammatory response in sepsis. The
      altered type of mucus glycoprotein physiologically secreted by alveolar
      epithelium and mucous parts of subepithelial seromucous glands of the bronchi
      with subsequent loss of a considerable proportion of protection of the mucosal
      barrier in sepsis may play an important additional role in the development of
      sepsis-induced lung injury.

PMID- 11964050
TI  - Incidence of chromosomal imbalances in advanced colorectal carcinomas and their
      metastases.
AB  - Comparative genomic hybridization (CGH) was used to screen 54 advanced colon
      carcinomas. i.e., 24 primary tumors and 30 metastases, for chromosomal
      alterations. Using a sensitive statistical method for the determination of DNA
      imbalances and histograms for analysis of the incidence of changes, we identified
      the DNA over-representation of chromosome 20q as the most common alteration being
      present in 100% of cases. High incidence deletions were observed on 18q21-18q23
      (96%), 4q27-4q28 (96%), 4p14 (87%), 5q21 (81%), 1p21-1p22 (72%), 21q21 (74%),
      6q16 (72%), 3p12 (66%), 8p24-8p21 (66%), 9p21 (64%), 11q22 (64%), and 14q13-14q21
      (64%). Further frequent over-representation was found on 7q12-7q11.2 (75%), 16p11
      16p12 (70%), 19p13 (70%), 9q34 (67%), 19q13 (67%), 13q34 (64%), 13q13 (64%),
      17q21 (59%), 22q11 (61%), 8q24 (57%), and 1q21 (57%). Pronounced DNA gains and
      losses being defined as regions in which the ratio profiles exceeded the values
      of 1.5 and 0.5, respectively, frequently colocalized with peaks of incidence
      curve. The use of difference histograms for the comparison of tumor subgroups as
      well as case-by-case histogram for the analysis of 15 paired tumor samples
      identified several of the above alterations as relevant for tumor progression and
      metastasis formation. The study identified additional loci and delineates more
      precisely those that have been previously reported. For comparative purposes, we
      have made our primary data (ratio profiles, clinicopathological parameters,
      histograms) available at the interactive web site http://amba.charite.de/cgh,
      where the incidence of changes can be determined at individual loci and
      additional parameters can be applied for the analysis of our CGH results.

PMID- 11964052
TI  - Pyloric gland-type tubular adenoma superimposed on intraductal papillary mucinous
      tumor of the pancreas. Pyloric gland adenoma of the pancreas.
AB  - We report a rare case of pyloric gland-type tubular adenoma of the main
      pancreatic duct. It was a grossly visible polypoid nodule and was composed of
      closely packed pyloric-type glands. This adenoma was present within an
      intraductal papillary mucinous adenoma (IPMA). In this IPMA lesion, aggregations
      of pyloric-type glands were occasionally observed, and most of the cells
      including ductal lining cells expressed pyloric gland-type mucin. The IPMA of the
      present case showed more extensive pyloric gland metaplasia or differentiation
      than commonly noted in IPMAs. We consider this pyloric gland-type tubular adenoma
      to be derived from a selective growth of IPMA cells showing pyloric gland
      metaplasia.

PMID- 11964051
TI  - Establishment of a transplantable tumor line (IP) derived from rat pulmonary
      carcinoma, developing humoral hypercalcemia of malignancy in IP-bearing rats.
AB  - A transplantable tumor line (IP) was established in syngeneic rats from a
      spontaneous pulmonary carcinoma found in a male F344 rat aged 25 months. A tissue
      fragment of IP grew into a nodule, 2-3 cm in diameter, 2-3 weeks after implant,
      and IP has been serially passed through 26 generations. Lined by cuboidal or
      columnar epithelial cells, the primary tumor consisted of completely alveolar
      architecture. However, IP tumors developed various growth patterns such as
      glandular, acinar, trabecular, cord, and solid, and consisting of epithelial
      cells showing cellular atypia. Ultrastructurally, neoplastic cells had
      microvilli, basement membranes, and desmosomes, and occasional cells possessed
      dense cytoplasmic granules. Interestingly, it was shown by the
      immunohistochemistry, the RT-PCR method, and immunoradiometric assay that IP
      tumor cells produce parathyroid hormone-related protein (PTHrP). During a 3-week
      observation period after implant, IP-bearing rats showed severe emaciation,
      hypercalcemia, and hypophosphatemia, as well as an increase in osteoclastic areas
      and a decrease in shaft thickness of the femurs. These were considered to be due
      to a marked elevation of plasma PTHrP levels. Furthermore, IP-bearing rats
      developed calcification in various organs including the kidneys, lungs, and
      heart. These findings in IP-bearing rats were similar to those of humoral
      hypercalcemia of malignancy (HHM) reported in human cancer patients. PTHrP plays
      a central role in the development of HHM, but the mechanisms of HHM remain poorly
      understood. IP may become a useful model for studying the pathogenesis of HHM and
      the pathophysiological role of PTHrP.

PMID- 11964053
TI  - Oligoclonality of a "composite" gastric diffuse large B-cell lymphoma with areas
      of marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type.
AB  - We analyzed a case of oligoclonal Helicobacter pylori-associated, primary gastric
      diffuse large B-cell lymphoma (DLBCL) with areas of extranodal marginal zone B
      cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT) type in a 61
      year-old male patient. The patient had two separate tumors, in the corpus and in
      the antrum, each showing two morphologically distinct components (DLBCL and MZBL
      of MALT type). To determine the clonal relationship between the large- and small
      cell components, we microdissected four samples from morphologically distinct
      tumor components at both tumor sites. PCR analysis revealed rearranged
      immunoglobulin heavy chain (IgH) genes of different sizes in three of the four
      microdissected samples. Cloning and sequencing of the PCR products displayed
      different IgH gene rearrangements in the two small cell components of the antrum
      and the corpus. A third genuinely differently rearranged IgH gene was found in
      the large-cell components of both antrum and corpus. Our results suggest that in
      primary gastric DLBCL with areas of MZBL of MALT type, the small-cell component
      may comprise more than one tumor clone. Furthermore, the large-cell component may
      evolve independently from coexisting MZBL.

PMID- 11964054
TI  - Evolutionary approaches to addiction: introduction.

PMID- 11964055
TI  - Fermenting fruit and the historical ecology of ethanol ingestion: is alcoholism
      in modern humans an evolutionary hangover?
AB  - In the field of addiction research, the possibility of ancestral exposure to
      psychoactive compounds has generally been excluded. A paleobiological approach to
      the human diet, however, illustrates the potential utility of historical data in
      interpreting modern-day addictive behaviors. Low-level dietary exposure to
      ethanol via ingestion of fermenting fruit has probably characterized the
      predominantly frugivorous anthropoid lineage for about 40 million years.
      Potentially adaptive primate behaviors associated with the natural occurrence of
      ethanol include the olfactory use of ethanol plumes to localize fruit crops, the
      use of ethanol as an appetitive stimulant to facilitate rapid consumption of
      transient nutritional resources, and the physiological exploitation of the
      caloric benefits of ethanol. Such behavioral and energetic advantages probably
      pertain to all animal taxa that consume fermenting fruit, and may have been
      retained in modern humans in spite of considerable dietary diversification over
      the last several million years. In contemporary human environments, excessive
      consumption of ethanol would then represent maladaptive cooption of ancestrally
      advantageous behaviors given essentially ad libitum access to a compound
      otherwise found only within scarce nutritional substrates. Epidemiologically
      demonstrated health benefits of low-level alcohol consumption are consistent with
      an ancient and potentially adaptive exposure of primate frugivores to this most
      common of the psychoactive substances.

PMID- 11964056
TI  - Psychotropic substance-seeking: evolutionary pathology or adaptation?
AB  - According to a conventional evolutionary perspective, the human propensity for
      substance use is the product of a 'mismatch' between emotional mechanisms that
      evolved in a past without pure drugs or direct routes of drug administration, and
      the occurrence of these phenomena in the contemporary environment. The primary
      purpose of this review is to assert that, contrary to the conventional view,
      humans have shared a coevolutionary relationship with psychotropic plant
      substances that is millions of years old. We argue that this 'deep time'
      relationship is self-evident both in the extant chemical-ecological adaptations
      that have evolved in mammals to metabolize psychotropic plant substances and in
      the structure of plant defensive chemicals that have evolved to mimic the
      structure, and interfere with the function, of mammalian neurotransmitters. Given
      this evidence, we question how emotional mechanisms easily triggered by plant
      toxins can have evolved. Our argument is also supported with archeological and
      historical evidence of substance use in antiquity suggesting that, for people in
      the past, psychotropic plant substances were as much a mundane everyday item as
      they are for many people today. Our second, and more speculative objective is to
      suggest provisional hypotheses of human substance-using phenomena that can
      incorporate the evolutionary implications of a deep time relationship between
      psychotropic substances and people. We discuss hypotheses of selective benefits
      of substance use, including the idea that neurotransmitter-analog plant chemicals
      were exploited as substitutes for costly, nutritionally constrained endogenous
      neurotransmitters. However, even if substance seeking was adaptive in the
      environment of our hominid ancestors, it may not still be so in the contemporary
      environment. Thus, the implications of our argument are not that the mismatch
      concept does not apply to human substance-using phenomena, but that it must be
      reconsidered and extended to incorporate the implications of a substance-rich,
      rather than substance-free, evolutionary past.

PMID- 11964057
TI  - Life-history theory and risky drinking.
AB  - AIMS: Life-history theory, a major theory related to evolutionary biology and
      behavioral ecology, is applied to analyze patterns in alcohol abuse and
      dependence. The life-history approach examines how intensity of reproductive
      competition affects the benefits and costs of risk-taking, which are typically
      greater for young men than for women or older men. We used this framework to
      predict demographic variation in hazardous patterns of alcohol use, assuming that
      they reflect risk-taking in general. DESIGN: This paper is a review of literature
      on demographic patterns in risky drinking and alcohol dependence. Predictions are
      generated using evolutionary analysis of risk-taking. Existing surveys of
      drinking behavior are reviewed, and findings are compared to predictions.
      FINDINGS: Results were generally consistent with predictions. The frequency of
      risky drinking and dependence is higher for men, and people of younger age,
      single marital status, childless parental status or unstable environmental
      resources. An exception is the effect of educational attainment. which is
      inconsistent. CONCLUSIONS: Risky drinking behavior, as with other forms of
      physical risk-taking, is more frequently observed in young men, and it increases
      where environmental instability is higher. The utility of life-history theory is
      compared to alternate conceptions of risky drinking and dependence. Implications
      of this perspective for research and clinical efforts are explored.

PMID- 11964058
TI  - Evolutionary underpinnings of excessive alcohol consumption.
AB  - Given our close phylogenetic relatedness, non-human primates, in principle, could
      serve as an ideal model for alcoholism. Indeed, many studies in both humans and
      rhesus macaques show relationships between excessive alcohol consumption,
      aggression and serotonergic function, as measured by concentrations of the
      principal metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA) in the
      cerebrospinal fluid (CSF). An important behavioral predictor of excessive alcohol
      consumption in both humans and rhesus monkeys is the propensity toward
      impulsivity. Integrating behavioral and neuroendocrine data from captive and semi
      free-ranging rhesus macaques, we posit that benefits derived from impulsive and
      aggressive behaviors in some contexts might contribute indirectly to the
      maintenance of traits involved in alcoholism and excessive alcohol intake.

PMID- 11964059
TI  - The self-perceived survival ability and reproductive fitness (SPFit) theory of
      substance use disorders.
AB  - A new theory of substance use disorders is proposed-the SPFit theory-that is
      based on evolutionary biology and adaptive systems. Self-perceived survival
      ability and reproductive fitness (SPFit) is proposed as a human psychobiological
      construct that prioritizes and organizes (i.e. motivates) behavior, but is highly
      vulnerable to temporary, artificial activation by drugs of abuse.
      Autoshaping/sign-tracking/feature positive phenomena are proposed to underlie the
      development of craving and expectations about drugs as the individual learns that
      abused drugs will easily and reliably inflate SPFit. The cortico-mesolimbic
      dopamine system and its modulating interconnections are viewed as the biological
      substrate of SPFit; it is proposed to be a survival and reproductive motivation
      system rather than a reward center or reward pathway. Finally, the concept of
      modularity of mind is applied to the SPFit construct. Although considerable
      empirical data are consistent with the theory, new research is needed to test
      specific hypotheses derived from SPFit theory.

PMID- 11964060
TI  - Evolution meets biopsychosociality: an analysis of addictive behavior.
AB  - Evolutionary theory can inform the biopsychosocial approach to addictive behavior
      through the use of adaptationist thinking, or how natural selection has shaped
      the mechanisms and processes underlying addiction. Covering how evolutionary
      theory relates to biology, psychology and sociality, this paper examines three
      components to drug use and abuse: a biological mechanism (mesolimbic dopamine), a
      developmental trajectory (attachment) and a social phylogeny (dominance,
      submission, social dependence). The paper argues for a salience (or wanting) view
      of the function of dopamine; outlines how attachment affects time perspective,
      closure of internal models and self-regulation; and examines how inequality
      affects drug abuse and how social dependence and manipulative behaviors can play
      a role in relationships with drugs. The article concludes with an analysis of how
      the adaptive approach applies to interventions against addictive behavior.

PMID- 11964061
TI  - The role of brain emotional systems in addictions: a neuro-evolutionary
      perspective and new 'self-report' animal model.
AB  - The evolutionary significance of neurochemical events in the brain has received
      minimal attention in the field of addiction research. Likewise, the general
      failure of neuroscientists to postulate how basic brain circuits might mediate
      emotional urges has retarded the development of scientific perspectives that
      could inform new inquiries into the underlying dynamics and treatment of
      addictions. In this paper, we revisit the argument that prototypically abused
      substances activate or alter specific emotional brain systems that were
      evolutionarily designed to signal potential increments or decrements in fitness.
      We then discuss two distinct emotional systems (reward seeking and separation
      distress) which may track different types of potential changes in fitness. Based
      on this evolutionarily inspired approach, we illustrate how a mammalian model of
      emotion (i.e. rodent ultrasonic vocalizations) may enable scientists to predict
      drug-related phenomena such as abuse potential, anatomical location of mediating
      neural substrates, and the psychological impact of withdrawal. We conclude by
      discussing some therapeutic and social implications of examining drug addiction
      processes with multiple emotional brain systems in mind.

PMID- 11964062
TI  - Evolution and addiction.

PMID- 11964063
TI  - Taking Darwin seriously: more than telling just so stories.

PMID- 11964064
TI  - Evolutionary psychobiology: any relevance for therapy?

PMID- 11964065
TI  - Reversible binding of glycolytic enzymes and size change in the actin-containing
      filaments of the frog skeletal muscle.
AB  - Electron microscopy was used in order to study the change of the actin-containing
      filaments when the bound glycolytic enzymes were removed by a high ionic strength
      solution. The effectiveness of the extraction medium was checked by estimating
      the aldolase activity released. Evidence was provided that the larger diameter of
      the actin filaments in the I-bands in comparison with the A-bands can be
      accounted for by the bound glycolytic enzymes.

PMID- 11964066
TI  - Sarcomeric visco-elasticity of chemically skinned skeletal muscle fibres of the
      rabbit at rest.
AB  - The giant muscle protein titin (connectin), contained in the gap filament that
      connect a thick filament to the Z-line in a sarcomere, is generally considered to
      be responsible for the passive force (tension) and visco-elasticity in resting
      striated muscle. However, whether it can account for all the features of the
      resting tension response remains unclear. In this paper, we examine the basic
      features of the 'sarcomeric visco-elasticity' in a single resting mammalian
      muscle fibre and attempt to account for various tension components on the basis
      of known structural features of a sarcomere. At sarcomere length of approximately
      2.6 microm, the force response to a ramp stretch of 2-5% is complex but can be
      resolved into four functionally different components. The behaviour displayed by
      the components ranges from pure viscous type (directly proportional to stretch
      velocity, ranging from 0.1 to 30 lengths s(-1)) to predominantly elastic type
      (insensitive to stretch velocity at 1-2 s time scale); simulations show two
      components of visco-elasticity with characteristically different relaxation
      times. The velocity-sensitive components (only) are enhanced by filament lattice
      compression (dextran - 500 kD) and by increased medium viscosity (dextran - 12
      kD); also, the relaxation time of visco-elasticity is longer with increased
      medium viscosity. Amplitude of all the components and the relaxation time of
      visco-elasticity are increased at longer sarcomere length (range approximately
      2.5 - 3.0 microm). The study, and quantitative analyses, extend our previous work
      on intact muscle fibres and suggest that the velocity-sensitive tension
      components in intact sarcomere arise from interactions between sarcomeric
      filaments, filament segments and inter-filamentary medium; the two components of
      visco-elasticity arise from distinct regions of titin (connectin) molecules.

PMID- 11964067
TI  - Cross-bridge cooperativity during isometric contraction and unloaded shortening
      of skeletal muscle.
AB  - Whether the two heads of skeletal muscle myosin work independently or
      cooperatively remains an open question in muscle biophysics. While individual
      myosin heads are sufficient for ATPase activity (Reisler (1980) J Mol Biol 138:
      93-107) and force production (Harada et al. (1987) Nature 326: 805-808), it has
      also been reported that in situ, the two heads of a myosin molecule work
      cooperatively (Chaen et al. (1986) J Biol Chem 261(29): 13,632-13,636). To
      examine the role of cross-bridge cooperativity on isometric contraction and
      unloaded shortening we progressively inactivated myosin cross-bridges via
      titration with para-phenylenedimaleimide. The resting fiber ATPase was measured
      to provide an estimate of the fraction of active cross-bridges remaining during
      the titration. Isometric force and unloaded shortening velocity decline more
      rapidly than the resting ATPase as the titration proceeds. This is inconsistent
      with models for independent force generation and suggests cooperative action of
      myosin cross-bridges when muscle is isometrically contracting or shortening under
      zero load. However the degree of cooperativity depends on the type of muscle
      activity. While isometric force declines in a manner consistent with pair-wise
      cooperative action of myosin heads, unloaded shortening velocity declines more
      rapidly (greater cooperativity). Therefore, myosin cross-bridges in situ may be
      capable of at least two types of cooperative interactions, pair-wise
      cooperativity (when isometric) and another form of cooperativity that is
      sensitive to longer range interactions transmitted from other cross-bridges in
      the ensemble (during unloaded shortening).

PMID- 11964069
TI  - Influence of early postnatal cold exposure on myofiber maturation in pig skeletal
      muscle.
AB  - Early after birth, piglets rely almost exclusively on muscular shivering
      thermogenesis to produce heat in the cold and this can possibly modulate skeletal
      muscle development. An experiment involving 10 individually housed piglets was
      conducted to determine the influence of cold (24-15 degrees C, D5C group) vs.
      thermoneutrality (34-30 degrees C, D5TN group) between birth and 5 days on myosin
      heavy chain (MyHC) polymorphism and metabolic characteristics of longissimus
      lumborum (LL) and rhomboideus (RH) muscles. Five additional piglets were
      sacrificed at birth. Piglets exposed to cold received 43% more artificial milk on
      a liveweight basis in order to achieve similar growth rates. D5C piglets produced
      93% more heat and exhibited intense shivering during the whole experiment.
      Contractile and metabolic characteristics of muscles were determined by
      immunocytochemistry, electrophoresis and enzyme activities. At least eight MyHC
      isoforms were detected, including atypical expressions of the alpha-cardiac and
      extraocular isoforms. Dramatic changes in MyHC composition, myofiber cross
      sectional area (CSA) and energy metabolism occurred between birth and 5 days.
      Cold exposure did not affect either the total number of fibers or the CSA, but it
      did influence muscle maturation. In particular, it increased the expression of
      alpha-cardiac and type I MyHC, and decreased that of fetal MyHC, confirming an
      acceleration in the rate of postnatal maturation. An increase in oxidative enzyme
      activities was observed in both muscles in the cold, whereas the activity of a
      glycolytic enzyme, lactate dehydrogenase, remained unchanged. Cold exposure also
      induced an increase in T3 plasma levels. The extent to which these changes are
      the result of sustained shivering or are due to the action of hormonal factors,
      such as thyroid hormones, are discussed.

PMID- 11964070
TI  - Myosin and SERCA isoform expression in denervated slow-twitch muscle of euthyroid
      and hyperthyroid rabbits.
AB  - Changes in the isoform patterns of myosin heavy chains (MHC) and Ca2+-ATPase
      (SERCA) were studied in long-term (72 days) denervated slow-twitch soleus muscles
      of euthyroid and hyperthyroid rabbits. MHC isoforms were separated
      electrophoretically. SERCA isoforms were assessed by electrophoretic separation
      of the trypsin-digested and phosphorylated fragments. Denervation led to
      pronounced slow-to-fast transitions with increases in the fast MHC and fast
      SERCA1a isoforms. Hyperthyroidism had no significant effect on the denervation
      induced changes in SERCA isoforms, but led to slight increases in the relative
      concentrations of the fast MHC isoforms. A high correlation existed between the
      relative concentrations of slow myosin and SERCA2a in both innervated euthyroid
      and hyperthyroid soleus muscles. This correlation, however, seems to be less
      tight in denervated soleus muscles.

PMID- 11964068
TI  - Phosphorylation of kinase-related protein (telokin) in tonic and phasic smooth
      muscles.
AB  - KRP (telokin), an independently expressed C-terminal myosin-binding domain of
      smooth muscle myosin light chain kinase (MLCK), has been reported to have two
      related functions. First, KRP stabilizes myosin filaments (Shirinsky et al.,
      1993, J. Biol. Chem. 268, 16578-16583) in the presence of ATP. Secondly, KRP can
      modulate the level of myosin light chain phosphorylation. In this latter role,
      multiple mechanisms have been suggested. One hypothesis is that light chain
      phosphorylation is diminished by the direct competition of KRP and MLCK for
      myosin, resulting in a loss of contraction. Alternatively, KRP, through an
      unidentified mechanism, accelerates myosin light chain dephosphorylation in a
      manner possibly enhanced by KRP phosphorylation. Here, we demonstrate that KRP is
      a major phosphoprotein in smooth muscle, and use a comparative approach to
      investigate how its phosphorylation correlates with sustained contraction and
      forskolin-induced relaxation. Forskolin relaxation of precontracted artery strips
      caused little increase in KRP phosphorylation, while treatment with phorbol ester
      increased the level of KRP phosphorylation without a subsequent change in
      contractility. Although phorbol ester does not induce contraction of phasic
      tissues, the level of KRP phosphorylation is increased. Phosphopeptide maps of
      KRP from both tissues revealed multiple sites of phosphorylation within the N
      terminal region of KRP. Phosphopeptide maps of KRP from gizzard were more complex
      than those for KRP from artery consistent with heterogeneity at the amino
      terminus and/or additional sites. We discovered through analysis of KRP
      phosphorylation in vitro that Ser12, Ser15 and Ser15 are phosphorylated by cAMP
      dependent protein kinase, mitogen-activated protein (MAP) kinase and glycogen
      synthase kinase 3 (GSK3), respectively. Phosphorylation by GSK3 was dependent
      upon prephosphorylation by MAP kinase. This appears to be the first report of
      conditional or hierarchical phosphorylation of KRP. Peptides consistent with such
      multiple phosphorylations were found on the in vivo phosphopeptide maps of avian
      KRP. Collectively, the available data indicate that there is a complex
      relationship between the in vivo phosphorylation states of KRP and its effects on
      relaxation in smooth muscle.

PMID- 11964071
TI  - Persistent tubular conduction in vacuolated amphibian skeletal muscle following
      osmotic shock.
AB  - The transverse (T-)tubules primarily function in conducting the action potentials
      that initiate excitation contraction coupling in skeletal muscle but may
      additionally subserve longer-term roles in volume regulation, membrane fusion and
      other trafficking processes. Osmotic shock thus both electrically detaches the T
      tubules from surface membrane ('detubulation') and produces tubular vacuolation.
      The present experiments separated these effects. An established, reference
      osmotic shock protocol that exposed muscles to Ca2+/Mg2+-Ringer and gradual
      cooling to 10 degrees C after 18 min in glycerol-Ringer accomplished significant
      detubulation (77.5+/-13.15%, mean +/- SEM; n = 4). In contrast, a test protocol
      conducted entirely at room temperature using Mg2+-rather than Ca2+/ Mg2+-Ringer
      yielded reduced (P < 0.05, post hoc Duncan's multiple range test) detubulation
      indices (1.67+/-1.67%, n = 6) statistically indistinguishable from findings in
      fibres spared osmotic shock. Yet both osmotic shocks caused a formation of closed
      vacuoles, demonstrated by Sulphorhodamine B trapping, that occupied statistically
      similar fractions of total fibre volume (reference procedure: 14.38+/-2.7%, n =
      6; test procedure: 13.36+/-2.00%, n = 22) in turn higher than determinations in
      control fibres (P < 0.05). The findings reconcile reports associating
      detubulation with vacuolation in osmotically shocked muscle [S. Nik-Zainal et al.
      (1999) J Muscle Res Cell Motil 20: 45-53; K.N. Khan et al. (2000) J Muscle Res
      Cell Motil 21: 79-90] with the persistence of tubular electrical activity in
      extensively vacuolated amphibian fibres following fatigue [J. Lannergren and H.
      Westerblad (1987) Acta Physiol Scand 129: 311-318; J. Lannergren et al. (1999) J
      Muscle Res Cell Motil 20: 19-32]. Furthermore test protocols produced higher
      densities of open vacuoles (13.38+/-2.33%, n = 9) than did reference protocols
      (6.66+/-1.63%, n = 20) contrary to their possible involvement in the
      electrophysiological changes. Abolition of tubular electrophysiological activity
      thus either follows or is independent of tubular vacuolation whilst sharing some
      of its underlying osmotic mechanisms.

PMID- 11964072
TI  - Tibialis anterior muscles in mdx mice are highly susceptible to contraction
      induced injury.
AB  - Skeletal muscles of patients with Duchenne muscular dystrophy (DMD) and mdx mice
      lack dystrophin and are more susceptible to contraction-induced injury than
      control muscles. Our purpose was to develop an assay based on the high
      susceptibility to injury of limb muscles in mdx mice for use in evaluating
      therapeutic interventions. The assay involved two stretches of maximally
      activated tibialis anterior (TA) muscles in situ. Stretches of 40% strain
      relative to muscle fiber length were initiated from the plateau of isometric
      contractions. The magnitude of damage was assessed one minute later by the
      deficit in isometric force. At all ages (2-19 months), force deficits were four-
      to seven-fold higher for muscles in mdx compared with control mice. For control
      muscles, force deficits were unrelated to age, whereas force deficits increased
      dramatically for muscles in mdx mice after 8 months of age. The increase in
      susceptibility to injury of muscles from older mdx mice did not parallel similar
      adverse effects on muscle mass or force production. The in situ stretch protocol
      of TA muscles provides a valuable assay for investigations of the mechanisms of
      injury in dystrophic muscle and to test therapeutic interventions for reversing
      DMD.

PMID- 11964074
TI  - Cumulative influence of elastin peptides and plasminogen on matrix
      metalloproteinase activation and type I collagen invasion by HT-1080 fibrosarcoma
      cells.
AB  - HT-1080 fibrosarcoma cells express at their plasma membrane the elastin-binding
      protein (EBP). Occupancy of EBP by elastin fragments, tropoelastin or XGVAPG
      peptides was found to trigger procollagenase-1 (proMMP-1) overproduction by HT
      1080 cells at the protein and enzyme levels. RT-PCR analysis indicated that
      elastin peptides did not modify the MMP-1 mRNA steady state levels, suggesting
      the involvement of a post-transcriptional mechanism. We previously reported that
      binding of elastin peptides to EBP induced other matrix metalloproteinases (MMP-2
      and MT1-MMP) expression. Since those peptides were here found to also accelerate
      the secretion of urokinase from HT-1080 cells, culture medium was supplemented
      with plasminogen together with elastin peptides at aims to induce or potentiate
      MMPs activation cascades. In such conditions, plasmin activity was generated and
      exacerbate proMMP-1 and proMMP-2 activation. As a consequence, elastin peptides
      and plasminogen-treated HT-1080 cells displayed a significant type I collagen
      matrix invasive capacity.

PMID- 11964073
TI  - Human myosin XVBP is a transcribed pseudogene.
AB  - A novel human myosin gene located at 17q25 was identified through evaluation of
      genomic DNA sequence and designated myosin XVBP since it resembled human myosin
      XVA. In humans, myosin XVBP along with an adjacent gene, Lethal Giant Larvae 2
      (LLGL2) appears to have arisen from a genomic duplication of a chromosomal
      interval that included LLGL and an ancestral myosin XV. Inspection of human
      myosin XVBP predicted amino acid sequence from genomic DNA revealed that 36 of
      the 131 conserved amino acid residues of the motor domain are substituted or
      deleted, including sequence changes within the regions involved in the binding of
      ATP and actin. Twelve myosin XVBP overlapping cDNAs from kidney and stomach mRNA
      samples were cloned and sequenced. Analyses of these myosin XVBP cDNAs revealed
      numerous additional disablements including translational reading frame shifts
      resulting in stop codons. From these data we conclude that myosin XVBP is a
      transcribed, unprocessed pseudogene.

PMID- 11964075
TI  - Morphometric analysis of liver macrophages in patients with colorectal liver
      metastasis.
AB  - Kupffer cells, residential liver macrophages, have binding sites for
      carcinoembryonic antigen (CEA), but their role in metastatic liver tumor
      progression has not been well addressed clinically. Liver macrophages were
      analyzed morphometrically and their relationship with CEA and tumor microvessel
      density (MVD) was examined in 71 patients who underwent macroscopic curative
      hepatectomy for metastatic liver tumors from colorectal cancer. In paraffin
      embedded sections, MVD was evaluated by CD34-positive cell counts, liver
      macrophages visualized using anti PG-M1 (CD68) antibody were analyzed, and
      membrane-bound CEA was assessed by immunoreactivity of tumor cells for CEA. The
      area of liver macrophages in peritumoral regions (43.0 +/- 11.6 microm2) was
      significantly larger than that in non-tumor regions (25.2 +/- 24.2 microm2) (P <
      0.0001). The liver macrophage density in peritumoral regions was 154 +/- 49 per
      field, and was significantly higher than in non-tumor regions (74 +/- 24 per
      field) (P < 0.001). The density and the area of liver macrophages had no
      correlation with serum CEA levels and the degree of tumor CEA expression. A weak
      positive correlation was observed between MVD and liver macrophage density (P =
      0.0104, Spearman rank correlation coefficient = 0.31). Cox multivariate
      regression analysis showed that MVD greater than 50 (P = 0.0233, hazard ratio =
      2.463), and the area of liver macrophages larger than 40.9 microm2 (P = 0.0485,
      hazard ratio = 2.127), were significant independent prognostic factors. The
      present morphometric analysis suggests that the liver macrophages are accumulated
      and activated in peritumoral regions in patients with colorectal liver metastasis
      and this accumulation and activation of liver macrophages, with which soluble or
      membrane-bound CEA might not be associated, are related with patients' poor
      prognosis.

PMID- 11964076
TI  - Regulation of melanoma cell migration and invasion by laminin-5 and alpha3beta1
      integrin (VLA-3).
AB  - We evaluated the role of soluble factors produced from epidermal cells in
      melanoma cell motility by using the Boyden chamber chemoinvasion system. The
      migration of two melanoma cell lines, A375 and Mewo, was potentiated by
      conditioned media of A431 epidermoid cells in a concentration-dependent manner.
      The enhancement of A375 melanoma cell motility induced by the conditioned medium
      was blocked by antibodies against either alpha3 or beta1 integrin subunit. The
      motility-stimulating activity was recovered in the same fraction as the alpha3
      integrin-dependent adhesion-promoting activity in a high-molecular-weight (>200
      kDa) fraction on Superose 12 gel chromatography, and adsorbed with an anti
      laminin-5 antibody. Purified laminin-5 was capable of potentiating melanoma cell
      migration as measured in either the chemotaxis assay with a soluble form of
      laminin-5 or the haptotaxis assay with membranes coated with a mixture of laminin
      5 and Matrigel. Furthermore, immobilized laminin-5 induced A375 melanoma cells to
      secrete matrix metalloproteinase-9 (type IV collagenase) into the culture medium.
      These results strongly suggest that the interaction of laminin-5 produced in the
      epidermis with alpha3beta1 integrin on melanoma cells is involved in cell
      migration, invasion, and degradation of extracellular matrix proteins.

PMID- 11964077
TI  - Interleukin-8 and vascular endothelial growth factor mRNA and protein levels are
      down-regulated in ovarian carcinoma cells in serous effusions.
AB  - Angiogenic factors are involved in tumor growth and spread. The aim of this study
      was to evaluate the expression of angiogenesis-related genes in malignant serous
      effusions of patients with advanced-stage (FIGO stage III and IV) ovarian
      carcinoma. In addition, to compare the results for carcinoma cells in effusions
      with corresponding primary tumors and metastatic lesions, and analyze their
      prognostic role. Sections from 66 effusions and 90 primary and metastatic lesions
      from 62 ovarian and primary peritoneal carcinoma patients, were evaluated for
      expression of basic fibroblast factor (bFGF), interleukin-8 (IL-8), and vascular
      endothelial growth factor (VEGF) using mRNA in situ hybridization (ISH). Protein
      expression was evaluated in a subset of specimens using immunohistochemistry
      (IHC). ISH results were correlated with clinical parameters. In both effusions
      and solid tumors, bFGF mRNA was the most commonly expressed factor (93% of
      effusions and 95% of solid tumors) followed by IL-8, while VEGF was expressed in
      a minority of the specimens (P < 0.001 for bFGF vs. IL-8 and VEGF). In solid
      tumors, angiogenic mRNA expression was seen in both tumor and stromal cells in
      the majority of positive cases. ISH results did not differ in primary and
      metastatic tumors. However, carcinoma cells in effusions showed down-regulated
      expression of VEGF, when compared with both primary tumors (P = 0.029) and
      metastases (P = 0.015). IL-8 showed a similar down-regulation in effusions, when
      compared with metastases (P = 0.005). IHC showed excellent agreement with mRNA
      findings on protein level. In the study of clinico-pathologic parameters, IL-8
      mRNA expression in effusions was associated with higher tumor grade (P = 0.044).
      Angiogenic gene expression in effusions showed no correlation with patient age,
      previous treatment, residual tumor size, FIGO stage or disease outcome in
      survival analysis (P > 0.05). Peritoneal and pleural effusions showed similar
      expression patterns. In conclusion, bFGF is the major angiogenic factor expressed
      in ovarian carcinoma at the mRNA level. It is highly expressed in both solid
      tumors and serous effusions, while IL-8 and VEGF are down regulated in carcinoma
      cells in effusions, possibly due to the lack of interaction with stromal cells.
      mRNA expression of VEGF, bFGF, and IL-8 does not appear to be a predictor of
      disease outcome in advanced-stage ovarian carcinoma. Carcinoma cells in pleural
      and peritoneal effusions show a similar metastatic expression profile, in
      agreement with our previous findings, supporting the true metastatic nature of
      ovarian carcinoma cells in ascites.

PMID- 11964078
TI  - Antiangiogenic and antimetastatic properties of Neovastat (AE-941), an orally
      active extract derived from cartilage tissue.
AB  - A novel naturally occurring antiangiogenic agent isolated from cartilage,
      referred to as Neovastat (AE-941), was examined for its efficacy against tumor
      neovascularization and progression. Exposure to Neovastat results in ex ovo
      antiangiogenic properties in the chorioallantoid membrane of chicken embryo (71%
      decrease in the angiogenic index as compared to the basic fibroblast growth
      factor (bFGF) treated control embryos, P < 0.0001). Oral administration of
      Neovastat inhibits bFGF-induced angiogenesis in the Matrigel mouse model (87.5%
      decrease in hemoglobin as compared to the bFGF-treated control implants, P <
      0.0001). Neovastat also induces a dose response decrease of lung metastases in
      the Lewis lung carcinoma model (oral administration; 69.1% of inhibition obtained
      at the maximal dose of 0.5 ml/day, P < 0.0001). Combined with a sub-optimal dose
      of cisplatinum (2 mg/kg, i.p.), Neovastat (0.5 ml/day) improved the therapeutic
      index by increasing the antimetastatic efficacy and by exerting a protective
      activity against cisplatinum-induced body weight loss and myelosuppression. In
      summary, our experimental data provide evidence of antiangiogenic and
      antimetastatic properties of Neovastat, following oral administration.

PMID- 11964079
TI  - Inhibition of endogenous carcinoembryonic antigen (CEA) increases the apoptotic
      rate of colon cancer cells and inhibits metastatic tumor growth.
AB  - It has been suggested that carcinoembryonic antigen (CEA) enhances metastatic
      seeding of colon cancer cells due to its homo- and heterophilic binding
      properties. Our recent finding that endogenous CEA protects colon cancer cells
      against apoptosis suggests a more complex role of CEA in cancer progression. In
      this study we compared the in vitro effects of endogenous CEA on tumor cell
      aggregation and cell cycle regulation of human HT29 colon cancer cells with the
      corresponding in vivo effects, i.e. tumor cell seeding and formation of
      metastatic lesions. Stable expression of CEA targeted ribozymes (Rz) under
      control of a tet-off promoter system allowed regulation of CEA levels on the mRNA
      and protein level by 50%. Downregulation of CEA levels inhibited tumor cell
      aggregation by 70%. In accordance with previous studies, reduction of CEA levels
      increased in vitro the apoptotic rate and reduced colony formation by 30% to 50%.
      To determine the in vivo effect of CEA-dependent aggregate formation and its
      growth regulating role under apoptotic stress, HT29 cells with high and low CEA
      levels, respectively, were injected into nude mice. Immunostaining of lung
      microsections revealed similar numbers of tumor cells one hour after injection.
      24 h later virtually all cells were removed from the lung in both groups.
      However, after 6 weeks all doxycycline treated mice (Rz off = CEA high) showed
      14.5 +/- 4.6 metastatic lung lesions/mouse while 0.2 +/- 0.2 lesions/mouse
      appeared in the untreated group (Rz on = CEA low) (P < 0.001). Our study
      demonstrates a multifunctional role of CEA and indicates a prometastatic role of
      CEA independent of its adhesive function possibly due to its anti-apoptotic
      function.

PMID- 11964080
TI  - Distinctive alterations of invasiveness, drug resistance and cell-cell
      organization in 3D-cultures of MCF-7, a human breast cancer cell line, and its
      multidrug resistant variant.
AB  - Growth of human tumor cells as three-dimensional (3D) multicellular spheroids
      modifies their invasive properties. Here we study the differences in the
      biological features of MCF-7, a human breast cancer cell line, and its multidrug
      resistant variant (MDR-MCF-7) cultured as spheroids or as monolayers. Three
      dimensional culture decreased the proliferative rate of both cell lines, reduced
      the drug sensitivity of MCF-7 cells and did not affect the resistance of MDR-MCF
      7 cells. Transmission electron microscopic studies and intercellular junctions
      labeling showed that MCF-7 spheroids had a junctional system involving E
      cadherin, tight-junctions and desmosomes. In MDR-MCF-7 cell spheroids, cell
      cohesion was mostly due to membrane interdigitations. MDR-MCF-7 cells, but not
      their parental counterpart, displayed a higher invasive potential when cultured
      as spheroids, as shown in the Boyden chamber assay. 3D-induced invasiveness was
      correlated with serine protease and plasminogen activator (PA) secretion. MCF-7
      cells did not show any tendency to invade, whatever the mode of culture. These
      results show that 3D-cultures as spheroids distinctively altered structural
      features of parental and MDR-MCF-7 cells. In MCF-7 cells, 3D-culture increased
      cell-cell contacts and drug resistance; in MDR-MCF-7 cells, it induced invasive
      properties.

PMID- 11964081
TI  - Effects of taurolidine and octreotide on port site and liver metastasis after
      laparoscopy in an animal model of pancreatic cancer.
AB  - Port site metastasis is a dreadful event following laparoscopy; however, the
      exact pathomechanism is still unknown. In order to prevent trocar metastasis we
      determined the effects of intraperitoneal lavage with either taurolidine or
      octreotide on port site and liver metastasis after laparoscopy in a chemically
      induced, solid pancreatic adenocarcinoma. Pancreatic adenocarcinoma was induced
      in 60 Syrian hamsters by weekly injection of 10 mg/kg body weight N-nitrosobis-2
      oxopropylamine s.c. for 10 weeks. Six weeks later, a laparoscopic pancreatic
      biopsy was performed by the use of a pneumoperitoneum with carbon dioxide (12 mm
      Hg), followed by an abdominal irrigation with 5 ml normal saline (group 1, n =
      20), 5 ml 0.5% taurolidine (group 2, n = 20) or 5 ml octreotide (20 mg/ml) (group
      3, n = 20). After 8 weeks, all hamsters were sacrificed and histopathologically
      examined. There was only one macroscopic visible primary tumor in the taurolidine
      group (5.9%), compared to 42.1% in the saline group and 62.5% in the octreotide
      group (P < 0.05). The size of carcinomas was smaller in the saline group than
      after octreotide irrigation (median 6, range 2-25 vs. median 70, range 40-160
      mm2, P < 0.05). The number of liver metastases per animal was increased after
      saline irrigation (median 4, range 2-6), compared to taurolidine (median 2, range
      1-3) or octreotide (median 2.5, range 2-4) (P < 0.05). Port site metastases were
      found in 36.8% after saline, in 37.5% after octreotide and in 0% after
      taurolidine irrigation (P < 0.05). Thus port site metastasis was effectively
      prevented by taurolidine irrigation after staging-laparoscopy in pancreatic
      cancer.

PMID- 11964083
TI  - Expression of the thrombin receptor PAR-1 correlates with tumour cell
      differentiation of pancreatic adenocarcinoma in vitro.
AB  - Patients with pancreatic cancer frequently suffer from thrombosis due to excess
      thrombin generation. Yet, the effects of thrombin on pancreatic cancer are still
      poorly understood. The thrombin receptor PAR-1 is responsible for cellular
      effects of thrombin. PAR-1 plays an important role in the progression of
      different solid tumours in vitro. In breast cancer the level of PAR-1 expression
      correlates with invasiveness. Our aim was to correlate PAR-1 mRNA and protein
      expression level with the grade of differentiation of pancreatic tissue and
      cancer cell lines. PAR-1 protein was not detectable in the epithelium of healthy
      pancreas. Analysis of PAR-1 protein expression by immunofluorescence staining of
      pancreatic cancer cell lines revealed a correlation to the grade of
      differentiation. Quantitative analysis of PAR-1 protein expression by Western
      Blot analysis confirmed these observations. Analysis of PAR-1 mRNA expression
      showed low levels in healthy pancreas compared to pancreatic cancer tissue and
      the pancreatic cancer cell line MIA PaCa-2. The level of PAR-1 mRNA differed up
      to 25 fold between the respective pancreatic cancer cell lines. The eminent
      differences in PAR-1 expression, both protein and mRNA, between healthy
      pancreatic tissue and pancreatic cancer in vivo and in vitro emphasise the
      putative role of PAR-1 in pancreatic cancer progression.

PMID- 11964082
TI  - Resistance to apoptosis is increased during metastatic dissemination of colon
      cancer.
AB  - Apoptosis dysfunction in metastases has been suggested to participate in their
      poor response to conventional anticancer treatments. To address this question, we
      have analyzed the sensitivity to cell death induced by non-steroid anti
      inflammatory drug, Sulindac, the most common drug used in colon cancer
      chemotherapy, 5-fluorouracil (5-FU) and the short chain fatty acid, butyrate (Bu)
      in cell lines derived from a primary colorectal tumor (ALT-I) as well as the
      liver (ALT-F) and the lymph-node (ALT-G) metastases. We have previously shown
      both in vitro by analyzing anchorage-independent cell proliferation and in vivo
      by subcutaneous injection into athymic nude mice that the ALT-F and ALT-G cells
      were more tumorigenic than the primary ALT-I cells. All these cell lines, derived
      from an untreated patient, were highly resistant to apoptosis induced by 5-FU and
      Sulindac but were sensitive to Bu-induced apoptosis. The resistance to apoptosis
      was, as quantified by the induction of caspase activity and the relative
      percentage of apoptotic cells, higher in the metastatic cell lines, than in the
      ALT cell line. When compared to the primary tumor, more anti-apoptotic bcl-2 and
      less pro-apoptotic bax were expressed in the liver and lymph node metastatic cell
      lines. Quite remarkably, the expression of bax was up-regulated during Bu
      treatment, a feature that could explain its powerful pro-apoptotic activity.

PMID- 11964084
TI  - Influence of polyamines on in vitro and in vivo features of aggressive and
      metastatic behavior by human breast cancer cells.
AB  - Increased cellular activity of ornithine decarboxylase (ODC), the first and rate
      limiting enzyme in polyamine (PA) synthesis, is an independent adverse prognostic
      factor for overall survival in human breast cancer, thus suggesting an important
      role for PA in tumor progression. The experiments presented here were designed to
      investigate the role of PA in invasion and metastasis, using the highly
      aggressive MDA-MB-435 and MDA-MB-231 human breast cancer cell lines.
      Administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor
      of ODC, significantly reduced, in a dose-dependent manner, the invasiveness in
      matrigel of both MDA-MB-435 and MDA-MB-231 cells by approximately 70%. DFMO
      treatment also inhibited (P < 0.0001) 'stellate' colony formation (an indicator
      of aggressive phenotype) by MDA-MB-435 cells plated in the matrigel outgrowth
      assay. Administration of DFMO (2% in drinking water) reduced the growth rate of
      both cell lines implanted orthotopically in nude mice. To evaluate metastasis
      while minimizing effects on proliferation, DFMO-treated mice were sacrificed
      later to allow their tumors to reach the same size of the tumors in the control
      mice. The most striking finding was that DFMO, while ineffective in reducing
      local invasion, nearly totally abolished (P = 0.0152) pulmonary metastasis in
      mice bearing MDA-MB-435 xenografts. These results support a role of PA in
      promoting breast cancer aggressiveness, particularly with regard to the
      development of distant metastasis. Furthermore, the data suggest that PA
      involvement is distal to local invasion in the metastatic cascade.

PMID- 11964085
TI  - The activity for the induction of the sperm acrosome reaction localises in the
      outer layers and exists in the high-molecular-weight components of the egg-jelly
      of the newt, Cynops pyrrhogaster.
AB  - Localisation of the acrosome reaction inducing activity in egg-jelly was examined
      in the newt, Cynops pyrrhogaster. The jelly has six layers: the J0, J1, J2, J3,
      J4 and st layers. Jelly was mechanically dissected and placed on a Millipore
      filter. When sperm were added from the outer surface side of the jelly, most of
      them exhibited the acrosome reaction after passing through the jelly. When egg
      jelly was divided into four layers, strong activity for the induction of acrosome
      reaction was detected in the outer layers, J4+st. These findings suggest that the
      acrosome reaction is induced by a substance in the outer layers of the egg-jelly.
      Among jelly components separated by SDS-PAGE, a fraction of more than 500 kDa in
      molecular weight induced the acrosome reaction. Wheat germ agglutinin (WGA),
      Griffonia simplicifoliar agglutinin 1 (GS-1), Maclura pomifera agglutinin (MPA)
      and Arachis hypogaea agglutinin (PNA) inhibited the induction of the acrosome
      reaction by jelly extract, and WGA did so in a dose-dependent manner. Those
      lectins precipitated some molecules of over 500 kDa. These results suggest that
      the acrosome reaction is induced by the high molecular-weight components of egg
      jelly in C. pyrrhogaster.

PMID- 11964086
TI  - Analysing mammalian fertilisation: reservations and potential pitfalls with an in
      vitro approach.

PMID- 11964087
TI  - Induction of apoptosis mediated by fas receptor and activation of caspase-3 in
      MRL-+/+ or MRL-lpr/lpr murine oocytes.
AB  - The molecular mechanisms leading to ovarian follicular atresia in the typical
      pathways of programmed cell death remain to be clarified. Here we have
      demonstrated that the apoptotic signalling pathway in MRL-+/+ (MRL/+) murine
      oocytes is through the Fas receptor followed by the activation of caspase-3. In
      contrast, we found that the aberrant expression and dysfunction of the mutant Fas
      receptor in MRL-lpr/lpr (MRL/lpr) murine oocytes caused by insertion of the early
      transposable element (ETn) into the Fas gene were associated with an inability to
      activate the caspase cascade (especially caspase-3) and to induce nuclear DNA
      fragmentation. These findings indicate that the induction of apoptosis in MRL/lpr
      murine oocytes did not occur in the presence of a defective Fas receptor lacking
      the death domain to trigger the caspase cascade, suggesting a failure to induce
      ovarian follicular atresia.

PMID- 11964088
TI  - Double copulation of a female with sterile diploid and polyploid males recovers
      fertility in Bombyx mori.
AB  - Silkworm males produce dimorphic sperm, nucleate eupyrene sperm and anucleate
      apyrene sperm. Apyrene sperm have been speculated to have an assisting role in
      fertilisation. However, the coexistence of eupyrene and apyrene sperm in the
      testis and female reproductive organs has made it difficult to define the role of
      apyrene sperm. Polyploid males are highly sterile. Microscopic observation
      revealed that the elimination of eupyrene nuclei by peristaltic squeezing caused
      the sterility of polyploids. Heat-shock applied to pupae of Daizo males (DH) also
      induced high sterility due to the lack of normal apyrene sperm. When eupyrene
      sperm of sterile DH males and apyrene sperm of sterile polyploid males were mixed
      by double copulation, a remarkable increase in fertility of the double-mated
      females was observed. This finding strongly suggests that the apyrene sperm are
      indispensable in fertilisation of the silkworm and that polyploid apyrene sperm
      function as a substitute for diploid sperm. We established an experimental system
      in which we can separate the two types of sperm for further studies on their
      functions without chemical and/or mechanical treatments.

PMID- 11964089
TI  - Activation of ribosomal S6 kinase (RSK) during porcine oocyte maturation.
AB  - The normal kinetics of ribosomal S6 kinase (RSK) during the meiotic maturation of
      porcine oocytes were examined. The phosphorylation states of RSK and
      extracellular signal-regulated kinase (ERK), major mitogen-activated protein
      (MAP) kinases in maturating porcine oocytes, were detected by Western blotting
      analysis. The S6 protein kinase activity was assayed using a specific substrate
      peptide which contained the major phosphorylation sites of S6 kinase. Full
      phosphorylation of RSK was correlated with ERK phosphorylation and was observed
      before germinal vesicle breakdown. S6 kinase activity was low in both freshly
      isolated and 20 h cultured oocytes. S6 kinase activity was significantly elevated
      in matured oocytes to a level about 6 times higher than that in freshly isolated
      oocytes. Furthermore, full phosphorylation of RSK was inhibited when oocytes were
      treated with U0126, a specific MAP kinase kinase inhibitor, in dose-dependent
      manner, indicating that RSK is one of the substrates of MAP kinase. These results
      suggest that the activation of RSK is involved in the regulation of meiotic
      maturation of porcine oocytes.

PMID- 11964090
TI  - Suppression of meiosis by inhibitors of m-phase proteins in horse oocytes with
      low meiotic competence.
AB  - Germinal vesicle (GV)-stage horse oocytes with diffuse chromatin are meiotically
      incompetent and degenerate in culture, whereas horse oocytes having condensed
      chromatin within the GV are meiotically competent. Degeneration of incompetent
      oocytes in culture may be related to premature GV breakdown, which could possibly
      be prevented by inhibition of m-phase protein activity. We examined the effects
      of 6-dimethylaminopurine (6-DMAP), butyrolactone and roscovitine on GV-stage
      horse oocytes. Culture in the presence of 2 mM 6-DMAP for 24 h suppressed meiosis
      (2% MI or MII compared with 38% for untreated oocytes). The proportion of GV
      stage oocytes having condensed chromatin was not different between 6-DMAP culture
      and directly fixed controls; however, the proportion of oocytes with diffuse
      chromatin was significantly lower, and more oocytes with diffuse chromatin had
      atypical chromatin than did controls (p < 0.01). Culture with butyrolactone at
      100 microM suppressed meiosis (5% MI + II). Again, this treatment maintained GV
      stage oocytes having condensed chromatin, but the proportion of oocytes with
      diffuse chromatin was significantly reduced compared with directly fixed controls
      (p < 0.05). Culture with roscovitine at 25 microM was also effective in
      maintaining GV-stage oocytes having condensed chromatin; however, culture with
      100 microM roscovitine did not suppress meiosis or maintain oocytes in the GV
      stage. These results indicate that meiosis in GV-stage horse oocytes having
      condensed chromatin may be suppressed by inhibitors of m-phase protein activity;
      however, oocytes originally having diffuse chromatin appear to degenerate in
      culture even in the presence of these inhibitors.

PMID- 11964091
TI  - Activation of pig and cattle oocytes by butyrolactone I: morphological and
      biochemical study.
AB  - In this study a specific inhibitor of cyclin-dependent kinases (cdks),
      butyrolactone I (BL I), was used for activation of pig and cattle metaphase II
      (MII) oocytes. BL I at a concentration of 100 microM was able to induce
      activation of both pig and cattle MII oocytes in a manner dependent on exposure
      time; however, precise timing of BL I exposure was required for the best
      activation results. The optimum activation rates were obtained when cattle MII
      oocytes were treated for 5 h with BL I and subsequently for 3-11 h in control
      medium, and pig MII oocytes for 8 h in BL I and then for 8-16 h in control
      medium; the percentage of activated oocytes after such treatment varied between
      55% and 74% and between 53% and 81% for cattle and pig oocytes, respectively.
      Shorter exposures to BL I led to re-entry of the oocytes to the metaphase state
      in 35-50% of oocytes, the remaining oocytes forming a pronuclear stage; longer
      exposure to BL I led to increased numbers of oocytes being abnormal or
      degenerated. The behaviour of histone H1 kinase and mitogen activated protein
      (MAP) kinase, also measured during the experiment, reflected the morphological
      changes in the oocytes: both were inactivated after BL I treatment, though the
      inactivation of histone H1 kinase occurred 2 h ahead of that of MAP kinase.
      However, in the oocytes treated for a shorter time with BL I, with the
      reoccurrence of condensed chromatin in proportion of the oocytes cultured in
      control medium after BL I treatment, both kinases became reactivated. Taken
      together, these results suggest the possibility of using BL I for activation and
      cloning experiments in both species.

PMID- 11964092
TI  - Oocyte Ca2+ spike acquisition during in vitro development of early preantral
      follicles: influence of age and hormonal supplementation.
AB  - Calcium signalling is involved in important events in oocytes, such as meiotic
      competence acquisition. We have previously demonstrated the positive influence of
      animal age and gonadotropin stimulation in vivo regarding the ability of oocytes
      recovered from preantral follicles to exhibit calcium spikes. In the present work
      we determined whether preantral follicle development in vitro also allows oocytes
      to acquire calcium signalling activity. We also aimed to verify the influence of
      animal age, FSH + LH and/or insulin on oocyte calcium spike acquisition during
      preantral follicle culture. Early preantral follicles were isolated from 12-day
      old and 1- to 3-month-old F1 hybrid mice and cultured individually for either 2
      or 6 days. At the end of the culture period the oocytes were processed for
      calcium imaging by confocal microscopy. We show that oocytes recovered from
      cultured preantral follicles exhibit variable calcium spike activity rates,
      depending on animal age, culture duration and hormonal supplementation. Oocytes
      recovered from adult animals continue to exhibit calcium spikes, and those
      recovered from juveniles acquire that activity after culture. Insulin and
      gonadotropins in combination account for an early and maintained inhibitory
      effect on calcium signalling acquisition by oocytes. Insulin alone also leads to
      an early inhibitory effect, which, however, disappears with longer culture
      periods. Contrary to the complex in vivo situation, the acquisition of calcium
      signalling by oocytes in a controlled in vitro environment does not seem to be
      dependent on gonadotropins alone.

PMID- 11964093
TI  - The effects of 17beta-estradiol and protein supplement on the response to
      purified and recombinant follicle stimulating hormone in bovine oocytes.
AB  - During in vitro maturation of bovine oocytes, effects of gonadotropins (FSH, LH)
      and growth factors such as epidermal growth factor (EGF) vary among studies. Now
      that we can use defined or semi-defined medium, it becomes possible to evaluate
      recombinant products to assess their roles. Therefore, this study was designed to
      evaluate the effect of purified porcine (pFSH) or recombinant human (r-hFSH; 5,
      50, or 500 ng/ml) follicle stimulating hormone, luteinising hormone (LH; 50,500
      or 5000 ng/ml) and epidermal growth factor (EGF; 5, 10, 30 or 50 ng/ml) on
      subsequent embryonic development of in vitro matured bovine oocytes. In addition,
      the presence of bovine serum albumin (BSA; 8 mg/ml) as a protein supplement
      during in vitro maturation (IVM) was studied. For all treatments, cumulus-oocyte
      complexes were matured in defined maturation medium consisting of synthetic
      oviduct fluid. Addition of LH to the maturation medium at all concentrations
      studied did not increase the proportion of oocytes developing to the morula and
      blastocyst stages. However, morula and blastocyst yield were improved (p < 0.05)
      after addition of EGF (30 ng/ml) as compared with maturation medium alone (29.3%
      vs 18.0%, respectively). Addition of r-hFSH to the maturation medium in the
      presence of 17beta-estradiol (E2) significantly (p < 0.0001) increased the morula
      and blastocyst rate compared with maturation medium alone (40.3% vs 19.3%,
      respectively). The presence of BSA alone during IVM significantly reduced the
      developmental competence of oocytes as reflected by the morula and blastocyst
      yield. These results demonstrate the essential role of FSH, EGF and E2 on the
      kinetics of nuclear and cytoplasmic maturation that are essential for the
      formation of an egg capable of fertilisation and development. Also,
      supplementation of r-hFSH and E2 during IVM under our conditions increases morula
      and blastocyst yield following in vitro fertilisation and in vitro culture in
      defined medium. Finally, the presence of BSA as the only protein supplement
      during IVM may be detrimental to oocyte maturation.

PMID- 11964094
TI  - The analysis of chromatin organisation allows selection of mouse antral oocytes
      competent for development to blastocyst.
AB  - Mouse antral oocytes can be classified in two different types termed SN or NSN
      oocytes, depending on the presence or absence, respectively, of a ring of Hoechst
      33342-positive chromatin surrounding the nucleolus. The aim of the present study
      was to test the developmental competence to blastocyst of the two types of
      oocytes. Here we show that following isolation, classification and culture of
      cumulus-free antral oocytes, 14.7% and 74.5% of NSN and SN oocytes, respectively,
      reached the metaphase II stage. When fertilised and further cultured none of the
      metaphase II NSN oocytes developed beyond the 2-cell stage whilst 47.4% of the
      metaphase II SN oocytes reached the 4-cell stage and 18.4% developed to
      blastocyst. The findings reported in this paper may contribute to improved
      procedures of female gamete selection for in vitro fertilisation of humans and
      farm animals. Furthermore, the selection of oocytes with better developmental
      potential may be of interest for studies on nuclear/cytoplasm interaction,
      particularly in nuclear-transfer experiments.

PMID- 11964095
TI  - Cyclin B1 levels in the porcine 4-cell stage embryo.
AB  - The relative quantity of cyclin B1 was determined during the development of in
      vitro and in vivo derived porcine 4-cell embryos by western blotting and
      immunolocalised during the 4-cell stage. After cleavage to the 4-cell stage
      cyclin B1 localised to the cytoplasm at the 5, 10, 18 and 25 time points and
      localised to the nucleus 33 h post 4-cell cleavage (P4CC). The relative abundance
      of cyclin B1 was not significantly different in in vivo or in vitro derived 4
      cell stage embryos cultured in the absence of the RNA polymerase inhibitor alpha
      amanitin. Cyclin B1 protein was not detectable in embryos cultured in medium
      without alpha-amanitin for 5, 10, 18 or 25 h P4CC followed by culture in medium
      with alpha-amanitin to 33 P4CC. These results suggest that the maternal to
      zygotic transition of mRNA production that occurs at the 4-cell stage of the pig
      embryo does not result in an increase in cyclin B1 production. In addition,
      cyclin B1 protein levels remained constant in the absence of embryonic genome
      activation at the 4-cell stage.

PMID- 11964096
TI  - Immunohistochemical localisation of growth hormone (GH), GH receptor (GHR),
      insulin-like growth factor I (IGF-I) and type I IGF-I receptor, and gene
      expression of GH and GHR in rat pre-antral follicles.
AB  - We previously demonstrated that the development of cultured rat pre-antral
      follicles is stimulated by growth hormone (GH) and insulin-like growth factor-I
      (IGF-I) and that the mRNA of IGF-I and type I IGF receptor (IGFR) is present in
      the oocyte and wall of these follicles. To gain a closer insight into the
      regulation of early folliculogenesis by GH and IGF-I, the present study
      investigated the gene expression of GH and GHR mRNA in isolated oocytes and
      follicular wall cells of pre-antral follicles, using reverse transcriptase
      polymerase chain reaction, and the localisation of immunoreactive IGF-I, IGFR, GH
      and GHR proteins in ovarian sections of 10-day-old rats. GH was detected in
      oocytes and follicular wall tissue of pre-antral follicles, whereas expression of
      the GH mRNA was absent. The GHR mRNA was present in follicular wall tissue and
      not in the oocyte, while positive immunostaining for GHR was observed in all
      cells of the pre-antral follicles. Immunoreactive IGF-I and IGFR was also visible
      in the pre-antral follicles, especially in the oocytes. In conclusion, the data
      show that the previously demonstrated local gene expression of IGF-I and IGFR in
      oocytes and their enveloping follicular cells also leads to translation, which
      points to the involvement of intrafollicular IGF-I in early follicular
      development. The presence of the GHR mRNA and the GHR and GH proteins in pre
      antral follicles in the absence of ovarian GH mRNA suggest a direct effect of
      systemic GH on early follicular development.

PMID- 11964097
TI  - Cannabis use and cancer.

PMID- 11964098
TI  - Have we evaluated addiction treatment correctly? Implications from a chronic care
      perspective.

PMID- 11964099
TI  - Methodological characteristics and quality of alcohol treatment outcome studies,
      1970-98: an expanded evaluation.
AB  - AIMS: To examine the methodological quality of the research literature examining
      treatment for alcohol use disorders. DESIGN: In total, 701 studies first reported
      between 1970 and 1998 were evaluated with a scoring system covering 19 areas of
      research quality. FINDINGS: Methodological quality improved from a score of 8.2
      out of a possible 28.5 in the 1970s, to 10.6 in the 1990s. Strengths included
      reporting the initial number of participants and conducting follow-ups of 12
      months or longer. Although the percentage of studies with adequate power also
      increased overall, the average statistical power of comparative studies to detect
      a medium-sized treatment effect was low (0.54). CONCLUSIONS: Areas with room for
      improvement include: ensuring that follow-up data are collected when respondents
      are not under the influence of alcohol, testing for differential dropout among
      treatment groups with respect to participant background characteristics,
      reporting the number of individuals being treated in the programs from which
      samples are drawn, noting the reliability and validity of measures used and
      conducting process analyses to examine potential mechanisms underlying treatment
      effects.

PMID- 11964100
TI  - Mesa Grande: a methodological analysis of clinical trials of treatments for
      alcohol use disorders.
AB  - AIM: A 3-year update with 59 new controlled trials is provided for the ongoing
      Mesa Grande project reviewing clinical trials of treatments for alcohol use
      disorders. The project summarizes the current evidence for various treatment
      approaches, weighting findings differentially according to the methodological
      strength of each study. DESIGN: The review includes 361 controlled studies that
      (1) evaluated at least one treatment for alcohol use disorders, (2) compared it
      with an alternative condition (such as a control group, a placebo, a brief
      intervention or an alternative treatment), (3) used a procedure designed to
      create equivalent groups before treatment and (4) reported at least one outcome
      measure of drinking or alcohol-related consequences. Studies were rated by two
      reviewers on 12 methodological criteria, and outcome logic was analyzed for the
      specific treatment modalities tested. FINDINGS: Methodological quality of studies
      was significantly but modestly correlated with the reporting of a specific effect
      of treatment. Among psychosocial treatments, strongest evidence of efficacy was
      found for brief interventions, social skills training, the community
      reinforcement approach, behavior contracting, behavioral marital therapy and case
      management. For the first time, two pharmacotherapies also appeared among the
      most strongly supported approaches: opiate antagonists (naltrexone, nalmefene)
      and acamprosate. Least supported were methods designed to educate, confront,
      shock or foster insight regarding the nature and causes of alcoholism.
      CONCLUSIONS: Treatment methods differ substantially in apparent efficacy. It
      would be sensible to consider these differences in designing and funding
      treatment programs.

PMID- 11964101
TI  - Brief interventions for alcohol problems: a meta-analytic review of controlled
      investigations in treatment-seeking and non-treatment-seeking populations.
AB  - Brief interventions for alcohol use disorders have been the focus of considerable
      research. In this meta-analytic review, we considered studies comparing brief
      interventions with either control or extended treatment conditions. We calculated
      the effect sizes for multiple drinking-related outcomes at multiple follow-up
      points, and took into account the critical distinction between treatment-seeking
      and non-treatment-seeking samples. Most investigations fell into one of two
      types: those comparing brief interventions with control conditions in non
      treatment-seeking samples (n = 34) and those comparing brief interventions with
      extended treatment in treatment-seeking samples (n = 20). For studies of the
      first type, small to medium aggregate effect sizes in favor of brief
      interventions emerged across different follow-up points. At follow-up after > 3-6
      months, the effect for brief interventions compared to control conditions was
      significantly larger when individuals with more severe alcohol problems were
      excluded. For studies of the second type, the effect sizes were largely not
      significantly different from zero. This review summarizes additional positive
      evidence for brief interventions compared to control conditions typically
      delivered by health-care professionals to non-treatment-seeking samples. The
      results concur with previous reviews that found little difference between brief
      and extended treatment conditions. Because the evidence regarding brief
      interventions comes from different types of investigation with different samples,
      generalizations should be restricted to the populations, treatment
      characteristics and contexts represented in those studies.

PMID- 11964102
TI  - Effectiveness of brief interventions proved beyond reasonable doubt.

PMID- 11964103
TI  - Researching the treatment of drinking problems: a call for external as well as
      internal validity.

PMID- 11964104
TI  - A need for comparability in review design: comment on three reviews of studies
      for alcohol use disorder treatment.

PMID- 11964105
TI  - Meta-analysis in alcohol treatment research: does it help us to know what works?

PMID- 11964106
TI  - Excess alcohol consumption and health outcomes: a 6-year follow-up of men over
      age 50 from the health and retirement study.
AB  - AIMS: This study examined the association of problem drinking history and alcohol
      consumption with the onset of several health conditions and death over a 6-year
      follow-up period. SETTING: We analyzed two waves of longitudinal data on men over
      50 who participated in the Health and Retirement Study, a nationally
      representative sample of people aged 51-61 and their spouses living in the United
      States in 1992. MEASUREMENTS: Five types of health outcomes--mortality, general
      health, functional status, cognitive status, and mental health--were examined.
      Drinking categories were based on average drinks per day (0, <1, 1-2, 3-4, 5+),
      with 5 + defined as 'very heavy drinking'. Problem drinking history was
      identified as 2+ affirmative responses to the CAGE questionnaire. We controlled
      for smoking and other factors at baseline. FINDINGS: Over the 6-year follow-up
      period, very heavy drinking at baseline quadrupled the risk of developing
      functional impairments (OR: 4.21 95%, CI: 1.67, 10.61). A problem drinking
      history increased the onset of depression (OR: 1.67 95% CI: 1.02, 2.74),
      psychiatric problems (OR: 2.15 95% CI: 1.47, 3.13) and memory problems (OR: 1.71
      95% CI: 1.14, 2.56). Heavy drinking among mature adults was not associated with
      increased incidence of other adverse health events (i.e. angina, cancer,
      congestive heart failure, diabetes, myocardial infraction, lung disease or
      stroke). CONCLUSION: Very heavy drinking and a problem drinking history greatly
      increased rates of onset of functional impairments, psychiatric problems and
      memory loss in late middle age for men who had not experienced these impairments
      at their initial interview.

PMID- 11964107
TI  - Adolescent part-time work and heavy drinking in Finland.
AB  - AIMS: To examine the relationship between part-time work and heavy drinking among
      Finnish adolescents. DESIGN, SETTING: The cross-sectional survey data (the School
      Health Promotion Survey, n = 47,568) were collected in classrooms in 2000.
      PARTICIPANTS: Finnish lower-level secondary school students from the 8th and 9th
      grades, aged 14-16 years. The response rate was 82%. MEASUREMENTS: Work
      intensity, work type and the frequency of heavy drinking obtained from self
      administered questionnaires. The relationship between work and heavy drinking was
      studied using polychotomous logistic regression models. FINDINGS: Compared with
      non-workers, adolescents working more than 10 hours per week had an increased
      risk of heavy drinking, and also the frequency of heavy drinking was connected
      with this intensive working. When gender, grade level, parental education, the
      employment status of the parents, family structure, economic situation of the
      family, the degree of urbanisation, parental control, steady dating. GPA and
      disposable allowance were adjusted for, the odds of weekly drunkenness were
      almost three times the odds of not reporting drunkenness among intensive workers
      compared with non-workers. When adjusted for other factors, some typical
      children's jobs marginally decreased a likelihood of heavy drinking. CONCLUSIONS:
      Work does seem not protect adolescents from heavy drinking. Although many
      relevant factors were controlled for the effect may, however, be mediated through
      factors not covered in the survey. Therefore, further clarification of the causal
      chains linking adolescent working and drinking is needed.

PMID- 11964108
TI  - Factors associated with non-fatal heroin overdose: assessing the effect of
      frequency and route of heroin administration.
AB  - AIMS: To examine risk factors associated with non-fatal heroin overdose,
      particularly frequency and route of heroin administration. DESIGN: Data from
      cross-sectional surveys were analysed as a case-control and as a case cross-over
      design. SETTING AND PARTICIPANTS: 2556 subjects treated for heroin dependence in
      164 outpatient facilities in Spain. MEASUREMENTS: Prevalence of overdose
      involving emergency care in the 12 months before treatment admission. CASE
      CONTROL DESIGN: Odds ratio (OR) adjusted by logistic regression. CASE-CROSSOVER
      DESIGN: Estimated relative risk (RR) of transient risk of injecting heroin.
      FINDINGS: The prevalence of overdose was 10%. In the case control analysis the
      cumulative risk of overdose increased as the frequency of heroin use decreased.
      However, among daily heroin users this risk increased as the frequency of heroin
      injection rose, with an OR of 6.0 (95% CI: 3.9-9.6) for daily injectors versus
      non-injectors. Sniffers had a higher risk than smokers among non-daily users, but
      not among daily users. Other factors associated with increased risk of overdose
      were: tranquilizers, alcohol or cocaine use, living in certain regions and being
      long-term HIV+ 0. In the case-crossover analysis, the RR for injecting heroin
      versus using other routes immediately before overdose was 15.9 (95% CI: 9.5
      26.6), and was much higher for non-daily heroin users than for daily users.
      CONCLUSIONS: These findings suggest that the rapid entry of a large quantity of
      heroin into the blood (as occurs when injecting) involves a high risk of
      overdose, especially when the heroin tolerance level is low (as occurs in
      sporadic users).

PMID- 11964109
TI  - European adolescent substance use: the roles of family structure, function and
      gender.
AB  - OBJECTIVES: The aim of this study was, first, to explore family structure and
      measures of family functioning in relation to adolescent substance use and
      secondly, to establish if these relationships differed according to gender or
      according to the city of origin of the sample. DESIGN, SETTING, PARTICIPANTS: The
      study surveyed pupils aged 14-15 years in representative samples drawn from five
      European cities: Newcastle upon Tyne, Dublin, Rome, Bremen and Groningen. Data
      were obtained on 3984 participants in relation to their substance use, living
      with both biological parents, confiding in parents and grandparents. and
      supervision, as well as other variables representing delinquency, social class
      and drug availability. RESULTS: Living with both parents was associated with
      reduced levels of drug use in four cities but not in Dublin, due perhaps to the
      high availability from peers in that city. It was not associated with reduced
      levels of regular drinking. The effect of confiding in mother was evident in all
      cities and in relation to substance use in general. However, when a delinquency
      variable was added to the logistic regressions, its significance in relation to
      polydrug use disappeared. Supervision was somewhat more important in relation to
      male than female drug use. CONCLUSION: Living with both parents is a less robust
      barrier to substance use than qualitative aspects of family life, particularly
      attachment to mothers. The latter is a robust inhibitor of substance use
      irrespective of regional differences in drug availability, weakening only in the
      face of more generally problematic behaviour. Perhaps because of their greater
      tendency to risk-taking or rule breaking, supervision appears more important for
      male than female drug use. These findings underscore the role of families, but
      especially that of mothers, in regulating the substance-related behaviour of
      young people.

PMID- 11964110
TI  - The Benzodiazepine Withdrawal Symptom Questionnaire: psychometric evaluation
      during a discontinuation program in depressed chronic benzodiazepine users in
      general practice.
AB  - BACKGROUND: The Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ, Tyrer et
      al. 1990) has been developed to measure distinct features of the benzodiazepine
      withdrawal syndrome. However, psychometric evaluations of this questionnaire are
      scarce. AIMS, SETTING: To evaluate the BWSQ during a discontinuation program
      carried out by general practitioners in 230 depressed chronic benzodiazepine
      users. FINDINGS: Reliability coefficients during the program were between 0.84
      and 0.88 and the test-retest correlations were between 0.75 and 0.88 during
      withdrawal. Mean scores of the BWSQ during withdrawal differentiated between
      completers and failures (p = 0.036). The factor structure underlying the items
      consisted of perceptual and sensory disturbances, dysphoric mood, muscular pain
      and memory loss. Low scores during the last phase of tapering off predicted no,
      or limited, use of benzodiazepines in the first years following discontinuation
      (p = 0.003). CONCLUSIONS: We found the BWSQ to measure symptoms during
      benzodiazepine withdrawal in a reliable way. Our findings indicate some construct
      validity for BWSQ. Low scores during withdrawal predict more limited future use
      of benzodiazepines.

PMID- 11964111
TI  - The role of functional social support in treatment retention and outcomes among
      outpatient adult substance abusers.
AB  - AIMS: The goals of this study were: (1) to compare patients with high and low
      functional social support at intake and 6 months later on various risk factors;
      (2) to test the stress-buffering role of functional social support on treatment
      outcomes, and (3) to determine whether levels of functional social support at
      intake predicted treatment retention. DESIGN: Consecutive admissions to an
      outpatient treatment program were assessed at intake (n = 206) and at 6 month
      follow-up (n = 172) using the Addition Severity Index (ASI). Patients completed
      questionnaires pertaining to social support, stress and psychological functioning
      both at intake and at 6 months. FINDINGS: Both high and low social support groups
      experienced marked declines in negative affect and in the severity of substance
      abuse over time. There were some group differences: for example, symptoms of
      depression and psychological distress were higher among patients with low social
      support at intake and at 6 months. Patients with low social support at intake
      reported higher severity of alcohol and drug abuse at 6 months. Hierarchical
      regression analyses showed that functional social support was a modest predictor
      of reductions in the severity of alcohol abuse at follow-up, after controlling
      for the number of days in treatment. Higher levels of social support explained a
      modest (6%) proportion of the variance in alcohol-related outcomes, but did not
      predict reductions in drug abuse. Survival analysis demonstrated that the rate of
      dropping out of treatment was significantly higher for patients with low social
      support. CONCLUSIONS: Higher functional social support at intake is a positive
      predictor of retention in treatment, and a modest predictor of reductions in
      alcohol intake, but not in drug use. Overall, social support accounts for a small
      percentage of the variance in drug/alcohol-related outcomes, underscoring the
      need for further research into variables accounting for treatment success and
      failure.

PMID- 11964112
TI  - Does 'unlearning' ever really occur: comment on Conklin & Tiffany.

PMID- 11964113
TI  - Is cue exposure cure exposure?

PMID- 11964114
TI  - Estimating prevalence of problematic drug use: comments on Frischer et al.

PMID- 11964115
TI  - Methadone-related deaths in Scotland: areas for concern.

PMID- 11964116
TI  - Overview: Development in bacteria: spore formation in Bacillus subtilis.
AB  - Like eukaryotes, bacteria possess complex developmental programs that drive
      environmental adaptation and morphological differentiation. In some species,
      these morphological changes are quite elaborate and result in major changes in
      cell appearance, including the formation of ornate appendages. The ease with
      which some bacteria can be manipulated makes them highly attractive model systems
      for developmental analysis. In this set of reviews, we tackle the best studied of
      these systems, spore formation in Bacillus subtilis. Construction of a spore
      initiates in response to starvation, takes each cell about 8 h and is directed by
      a tightly controlled genetic program. First, the cell creates an internal
      protoplast with its own copy of the chromosome. Over the next several hours,
      development continues as proteins synthesized within the protoplast as well as in
      the surrounding cell cytoplasm coalesce into the various complex structures that
      comprise the spore. The resulting cell is metabolically dormant and as close to
      indestructible as any cell found on earth. Nonetheless, the spore retains the
      ability to revive almost immediately when nutrient returns to the environment.
      Here, we review the genetic control of spore formation, the structure and
      assembly of several major spore components, the process of germination, and the
      environmental and disease implications of spores. As these reviews document,
      spore formation in B. subtilis has been among the most productive systems for
      understanding both the broad themes and the molecular basis of development. Not
      only does this system continue to add to our understanding of these questions,
      but it provides a particularly powerful means to address the cell biological
      dimension of development.

PMID- 11964117
TI  - Bacillus subtilis sporulation and stationary phase gene expression.
AB  - Bacillus subtilis cells entering stationary phase due to nutrient deprivation
      have a number of options. Complex interconnected regulatory circuits govern
      differential gene expression patterns that channel the cell along the path it has
      sensed is most advantageous for survival in the environment. The actual choice
      depends upon the activity of an elaborate signal transduction network (the
      phosphorelay) that ultimately affects the activity of two key transcription
      factors, SpoOA and AbrB. Should the cell commit to sporulation, a temporally and
      spatially controlled cascade of RNA polymerase sigma factors leads to the
      development and release of an endospore from within the terminally
      differentiated, apoptotic mother cell.

PMID- 11964118
TI  - Spore germination.
AB  - Despite being relatively insensitive to environmental insult, the spore is
      responsive to low concentrations of chemical germinants, which induce
      germination. The process of bacterial spore germination involves membrane
      permeability changes, ion fluxes and the activation of enzymes that degrade the
      outer layers of the spore. A number of components in the spore that are required
      for the germination response have been identified, including a spore-specific
      family of receptor proteins (the GerA family), an ion transporter and cortex
      lytic enzymes. The germinant traverses the outer layers of the spore and
      interacts with its receptor in the inner membrane to initiate the cascade of
      germination events, but the molecular details of this signal transduction process
      remain to be identified.

PMID- 11964119
TI  - Roles of Bacillus endospores in the environment.
AB  - The occurrence and diverse roles of Bacillus spp. and their endospores in the
      environment is reviewed, with particular emphasis on soil ecology, host-symbiont
      and host-parasite interactions, and human exploitation of spores as biological
      control agents and probiotics.

PMID- 11964121
TI  - Specialized peptidoglycan of the bacterial endospore: the inner wall of the
      lockbox.
AB  - A modified peptidoglycan (PG) wall is required for maintenance of spore core
      dehydration and the accompanying metabolic dormancy and heat resistance.
      Production of the spore PG depends on the cooperative expression of gene products
      within both the mother cell and forespore compartments of the sporangium.
      Structural elements that differentiate spore PG from vegetative cell PG include
      the presence of the modified sugar muramic-delta-lactam and a low level of
      peptide cross-links between the glycan strands. Detailed analyses of PG structure
      in dormant spores and in developing forespores of wild-type and mutant strains
      are providing data on factors required for introduction of these modifications
      and the importance of these structural elements in determining spore properties.
      Muramic-delta-lactam is not required for spore core dehydration but serves as a
      specificity factor for spore germination lytic enzymes. Cross-linking of spore PG
      can vary over a relatively wide range without significantly effecting spore core
      dehydration but does have an influence on the rate of spore germination and
      outgrowth. Future studies will examine how the two cells within the sporangium
      coordinate the production of this unique structure between themselves and how
      specific spore PG structural modifications are produced and participate in
      determining spore resistance properties.

PMID- 11964120
TI  - Sporulation and delta-endotoxin synthesis by Bacillus thuringiensis.
AB  - Bacillus thuringiensis is distinguished from the very closely related Bacillus
      cereus and Bacillus anthracis by the presence of several plasmid-encoded delta
      endotoxin genes. These delta-endotoxins, synthesized as protoxins, are produced
      in large quantities during sporulation and are packaged into intracellular
      inclusions. Ingestion of the inclusions by insect larvae leads to protoxin
      solubilization and conversion to toxins each specific for one of several orders
      of insects. The toxins form cation-selective channels in the membrane of cells
      lining the larval midgut with subsequent lethality. In most cases, delta
      endotoxin synthesis and sporulation are closely coupled. The latter process in B.
      thuringiensis is probably virtually identical to that in Bacillus subtilis with
      the additional use of mother cell sporulation forms of RNA polymerase for the
      synthesis of the delta-endotoxins. There are other more subtle plasmid-encoded
      functions or plasmid interactions related to regulating protoxin synthesis.
      Consideration of both plasmid and chromosomal genes is thus critical for defining
      this organism.

PMID- 11964122
TI  - Assembly and genetics of spore protective structures.
AB  - The sporulation program in Bacillus subtilis ends in the formation of a highly
      resistant endospore that can withstand extremes of heat, mechanical disruption,
      ultraviolet irradiation, lytic enzymes and chemical attack. These properties are
      attributed mainly to the unique structure of spore coat and cortex, as well as to
      the physical state of the spore cytoplasm. The outermost layer of the spore,
      called the coat, has two morphologically distinct sublayers: an electron-dense
      outer coat and an electron-translucent inner coat. The coat is composed of more
      than 2 dozen proteins of varying size. Many coat genes and coat proteins have
      been isolated and characterized in detail, and studies of these have identified
      proteins with important roles in coat assembly, resistance and spore germination.
      We describe here characteristics of the coat proteins and propose a model for
      coat assembly based on recent work.

PMID- 11964123
TI  - The role of glycosylation in protein antigenic properties.
AB  - Glycosylation of proteins is a common event and contributes to protein antigenic
      properties. Most data have been obtained from model studies on glycoprotens with
      well-defined structure or synthetic glycopeptides and their respective monoclonal
      antibodies. Antibodies raised against glycoprotein antigens may be specific for
      their carbohydrate units which are recognized irrespective of the protein carrier
      (carbohydrate epitopes), or in the context of the adjacent amino acid residues
      (glycopeptidic epitopes). Conformation or proper exposure of peptidic epitopes of
      glycoproteins is also frequently modulated by glycosylation due to intramolecular
      carbohydrate-protein interactions. The effects of glycosylation are broad:
      glycosylation may 'inactivate' the peptidic epitope or may be required for its
      reactivity with the antibody, depending on the structure of the antigenic site
      and antibody fine specificity. Evidence is increasing that similar effects of
      glycosylation pertain to T cell-dependent cellular immune responses. Glycosylated
      peptides can be bound and presented by MHC class I or II molecules and elicit
      glycopeptide-specific T cell clones.

PMID- 11964124
TI  - Novel regulation and function of Src tyrosine kinase.
AB  - Src tyrosine kinase is a critical signal transducer that modulates a wide variety
      of cellular functions. Misregulation of Src leads to cell transformation and
      cancer. Heterotrimeric guanine-nucleotide-binding proteins (G proteins) are
      another group of signaling molecules that transduce signals from cell-surface
      receptors to generate physiological responses. Recently, it was discovered that G
      alpha s and G alpha i could directly stimulate Src family tyrosine kinase
      activity. This novel regulation of Src tyrosine kinase by G proteins provides
      insights into the adenylyl cyclase-independent signaling mechanisms involved in
      ligand-induced receptor desensitization, internalization and other physiological
      processes.

PMID- 11964125
TI  - Dietary n-3 polyunsaturated fatty acids and coronary heart disease-related
      mortality: a possible mechanism of action.
AB  - Epidemiological and interventional studies indicate that dietary n-3 PUFA reduces
      mortality due to coronary heart disease (CHD). They act at a low dose, since one
      or two meals with fatty fish per week is sufficient to provide protection when
      compared with no fish intake. These fatty acids are effective in providing
      primary prevention in low- and high-risk subjects and secondary prevention. At
      high doses, dietary n-3 PUFAs have several beneficial properties. First, they act
      favourably on blood characteristics: they are hypocholesterolemic and
      hypotriglyceridemic; they reduce platelet aggregation; they exhibit
      antithrombotic and fibrinolytic activities; they reduce blood viscosity and they
      exhibit antiinflammatory action. Second, they reduce ischemia/reperfusion-induced
      cellular damage. This effect is apparently due to the incorporation of
      eicosapentaenoic acid in membrane phospholipids. Third, they reduce ischemia and
      reperfusion arrhythmias. All the effects exerted by n-3 PUFAs at high doses are
      incompatible with the beneficial action on CHD mortality in humans observed at
      low doses, where their main properties are related to circulation in the form of
      free fatty acids. Numerous experimental studies have indicated that low
      concentrations of exogenous n-3 PUFAs reduce the severity of cardiac arrhythmias.
      This effect is probably responsible for the protective action of n-3 PUFA on CHD
      mortality. Further studies are necessary to confirm this assumption in animals.
      Such studies should take account of the fact that only a low dose of n-3 PUFA (20
      mg/kg/day) is necessary to afford protection. Furthermore, since the beneficial
      effect of n-3 PUFAs on CHD mortality is observed in fish eaters versus no-fish
      eaters, and since populations in industrialised countries consume excess n-6
      PUFAs, control animals in long-term dietary experiments should be fed a diet with
      only n-6 fatty acids as a source of PUFAs.

PMID- 11964126
TI  - Glycoprotein IIb/IIIa antagonists--from bench to practice.
AB  - The central role played by the alphaIIb beta3 receptor in platelet aggregation,
      and hence in platelet thrombosis, has led to the development of a number of
      parenteral and oral glycoprotein (GP) IIb/IIIa inhibitors for use in
      cardiovascular disease states, such as acute coronary syndromes and stroke. The
      predominant effect of these agents is to inhibit platelet aggregation, although
      studies of alphaIIb beta3 receptor function and various GP IIb/IIIa inhibitors
      have demonstrated the potential for these agents to produce effects on other
      aspects of platelet function, in addition to non-platelet effects. Overall,
      clinical studies have demonstrated an impressive beneficial effect for parenteral
      agents in reducing ischemic complications following percutaneous intervention,
      and a more modest beneficial effect in the treatment of patients with acute
      coronary syndromes. Trials with oral GP IIb/IIIa inhibitors in similar patient
      populations have demonstrated toxicity, manifested by an increased mortality in
      treated patients. Increased understanding of molecular aspects of both alphaIIb
      beta3 receptor function and the effects of GP IIb/IIIa inhibition may help
      explain some of the inconsistency in recently reported clinical studies with
      parenteral agents, and the frank toxicity of oral agents. Such studies may also
      hold the key to the development of newer agents with enhanced therapeutic
      benefit.

PMID- 11964127
TI  - Hormone-induced subcellular redistribution of trimeric G proteins.
AB  - Trimeric guanine nucleotide-binding proteins (G proteins) function as the key
      regulatory elements in a number of transmembrane signaling cascades where they
      convey information from agonist-activated receptors to effector molecules. The
      subcellular localization of G proteins is directly related to their functional
      role, i.e., the dominant portion of the cellular pool of G proteins resides in
      the plasma membrane. An intimate association of G protein subunits with the
      plasma membrane has been well known for a long time. However, results of a number
      of independent studies published in the past decade have indicated clearly that
      exposure of intact target cells to agonists results in subcellular redistribution
      of the cognate G proteins from plasma membranes to the light-vesicular membrane
      fractions, in internalization from the cell surface into the cell interior and in
      transfer from the membrane to the soluble cell fraction (high-speed supernatant),
      i.e., solubilization. Solubilization of G protein a subunits as a consequence of
      stimulation of G protein-coupled receptors (GPCRs) with agonists has also been
      observed in isolated membrane preparations. The membrane-cytosol shift of G
      proteins was detected even after direct activation of these proteins by non
      hydrolyzable analogues of GTP or by cholera toxin-induced ADP-ribosylation. In
      addition, prolonged stimulation of GPCRs with agonists has been shown to lead to
      down-regulation of the relevant G proteins. Together, these data suggest that G
      proteins might potentially participate in a highly complex set of events, which
      are generally termed desensitization of the hormone response. Internalization,
      subcellular redistribution, solubilization, and down-regulation of trimeric G
      proteins may thus provide an additional means (i.e., beside receptor-based
      mechanisms) to dampen the hormone or neurotransmitter response after sustained
      (long-term) exposure.

PMID- 11964128
TI  - Characterization of carrot pectin methylesterase.
AB  - The most alkaline form of pectin methylesterase was purified from ripe carrot
      roots and used for structural analysis. Determination of an N-terminal blocking
      group and of the primary structure allowed comparisons with other forms, and
      facilitated crystallographic determination of the three-dimensional structure.
      The mature enzyme has 319 residues and the N-terminal blocking group was shown to
      be a pyroglutamyl residue derived from a glutaminyl cyclization. Few other
      methylesterases have been isolated and assigned to exact mature forms, and
      together with the present enzyme, only two have been analyzed in three
      dimensional structure. However, comparison of 39 forms, mainly from GenBank data,
      reveals clear relationships and identifies subgroups of this enzyme type,
      deviating in structure but centering around two functionally important and
      conserved Asp residues at positions 136 and 157 in the carrot enzyme.

PMID- 11964129
TI  - Long-term sequelae of perinatal asphyxia in the aging rat.
AB  - Information on the consequences of perinatal asphyxia (PA) on brain morphology
      and function in the aging rat is missing although several groups have
      hypothesized that PA may be responsible for neurological and psychiatric deficits
      in the adult. We therefore decided to study the effects of PA on the central
      nervous system (CNS) in terms of morphology, immunohistochemistry, neurology and
      behavior in the aging animal. Hippocampus and cerebellum were evaluated
      morphologically by histological, immunohistochemical and magnetic resonance
      imaging and cerebellum also by stereological tests. Neurological function was
      tested by an observational test battery and rota rod test. Cognitive functions
      were examined by multiple-T-maze and the Morris water maze (MWM). Increased
      serotonin transporter (SERT) immunoreactivity in the CA2 region of the
      hippocampus and a significant difference in the escape latency, when the platform
      of the MWM was moved to a new location, were observed in asphyxiated rats. We
      showed that deteriorated cognitive functions accompanied by aberrant expression
      of hippocampal SERT and impaired relearning are long-term sequelae of perinatal
      asphyxia, a finding that may form the basis for understanding CNS pathology in
      the aging subject, animal or human.

PMID- 11964130
TI  - Expression of nerve growth factor-like polypeptides and immunoreactivity related
      to the two types of neurotrophin receptors in earthworm tissues.
AB  - Nerve growth factor (NGF) belongs by sequence homology to the neurotrophins, a
      family of proteins binding the same p75 receptor and closely related members of
      the Trk family of receptor tyrosine kinases. Fundamental in the vertebrate
      nervous system, neurotrophin signals have also been suggested as essential for
      relatively complex nervous systems occurring in invertebrate species that live
      longer than Caenorhabditis elegans and Drosophila melanogaster. Mammalian
      neurotrophins have been found to influence invertebrate neuronal growth. However,
      there are only a few data on the presence of molecules related to neurotrophin
      signalling components in invertebrates. Our studies provide evidence that
      analogues of neurotrophins and neurotrophin receptors are expressed in Eisenia
      foetida earthworms. In particular, NGF-like and Trk-like immunoreactive proteins
      are both expressed in the nervous system, whereas p75-like positivity identifies
      tubular structures associated with dorsal pores that are involved in the
      earthworm response to mechanical irritation or stress.

PMID- 11964131
TI  - Thyroid hormone controls carnitine status through modifications of gamma
      butyrobetaine hydroxylase activity and gene expression.
AB  - The carnitine system plays a key role in beta-oxidation of long-chain fatty acids
      by permitting their transport into the mitochondrial matrix. The effects of
      hypothyroidism and hyperthyroidism were studied on gamma-butyrobetaine
      hydroxylase (BBH), the enzyme responsible for carnitine biosynthesis in the rat.
      In rat liver, BBH activity was decreased in the hypothyroid state and increased
      in hyperthyroid animals. The modifications in BBH activity correlated with
      changes in the enzyme Vmax values. These changes were shown to be related to
      hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid
      metabolism, in particular by increasing long-chain fatty acid oxidation through
      activation of carnitine-dependent fatty acid import into mitochondria. Our study
      showed that thyroid hormones also increased carnitine bioavailability.

PMID- 11964132
TI  - Prevention of peroxynitrite-dependent damage by carnosine and related
      sulphonamido pseudodipeptides.
AB  - The naturally occurring dipeptides carnosine and anserine have been proposed to
      act as antioxidants in vivo. We investigated whether these compounds can act as
      protective agents able to counteract peroxynitrite-dependent reactions. The
      results showed that the dipeptides efficiently protect tyrosine against
      nitration, alpha1-antiproteinase against inactivation and human low-density
      lipoprotein against modification by peroxynitrite. Carnosine exerts its
      protective effect at concentrations similar to those found in human tissues. In
      addition, some synthetic pseudodipeptides, stucturally related to carnosine but
      stable to hydrolytic enzymes, possess protective properties against peroxynitrite
      dependent damage similar to the natural dipeptides. These pseudodipeptides may
      represent stable mimics of the biologically active carnosine suitable for
      pharmacological applications.

PMID- 11964133
TI  - Identification and characterisation of two allelic forms of human alcohol
      dehydrogenase 2.
AB  - The human alcohol dehydrogenase system is comprised of multiple forms that
      catalyse the oxidation/reduction of a large variety of alcohols and aldehydes. A
      transition that results in an Ile308Val substitution was identified in the human
      ADH2 gene by single-strand conformation polymorphism analysis. Screening a
      Swedish population revealed that Val308 was the most frequent allele (73%), and
      site-directed mutagenesis was used to obtain both allelozymes, which were
      expressed in Escherichia coli for characterisation. Thermostability was assayed
      by activity measurements and circular dichroism spectroscopy. The results showed
      that the 308Val substitution decreases protein stability, as compared to the
      Ile308 variant, an effect also demonstrated during prolonged storage. Ethanol,
      octanol, 12-hydroxydodecanoic acid and all-trans retinol were used as model
      substrates and, generally, slightly higher Km values were observed with Val at
      position 308. Finally, homology modelling, from mouse ADH2, further supported the
      decreased stability of the Val308 variant and located position 308 in the subunit
      interface of the molecule and in the vicinity of the active-site pocket entrance.
      In conclusion, the Ile308Val substitution represents a novel functional
      polymorphism within the human alcohol dehydrogenase gene cluster that may affect
      the metabolism of ethanol and other substrates.

PMID- 11964134
TI  - The interleukin-10-1082 G/A polymorphism: allele frequency in different
      populations and functional significance.
AB  - Genotypic variation in the human interleukin-10 (IL-10) promoter may account for
      marked inter-individual variation in IL-10 production and may influence
      susceptibility to autoimmune diseases. The G/A polymorphism at position -1082 has
      been linked to high/low IL-10 producer status. We directly tested the functional
      significance of this polymorphism using DNA-binding assays and reporter gene
      assays, examined allele frequencies in two geographically distinct populations
      and assessed intra- and inter-individual variation in IL-10 production in vitro
      according to genotype. Functional analyses showed that the -1082 region contains
      a putative ETS-like transcription factor-binding site, and nuclear factors from a
      monocyte cell line bind to this region. Transient transfection studies in an
      Epstein-Barr virus-transformed B cell line indicated that the -1082 A allele
      confers a two fold increase in transcriptional activity of the IL-10 promoter
      compared to the G allele. There was marked inter-individual variation in IL-10
      production by peripheral blood mononuclear cells in vitro, with no consistent
      effect of genotype.

PMID- 11964135
TI  - Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues:
      evidence for a morphine 6 glucuronide opiate receptor subtype.
AB  - We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate
      alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate
      receptor subtype fragments exhibiting high sequence similarity to those found in
      mammals. Now we demonstrate that M6G stimulates pedal ganglia constitutive nitric
      oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to
      similar peak levels as morphine. However, the classic opiate antagonist,
      naloxone, only blocked the ability of morphine to stimulate cNOS-derived NO
      release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability
      of M6G to induce cNOS-derived NO release as well as that of morphine, suggesting
      that a novel mu opiate receptor was present and selective toward M6G. In
      examining a receptor displacement analysis, both opiate alkaloids displaced [3H]
      dihydromorphine binding to the mu opiate receptor subtype. However, morphine
      exhibited a twofold higher affinity, again suggesting that a novel mu opiate
      receptor may be present.

PMID- 11964136
TI  - Sexual functioning and SSRIs.
AB  - This article reviews the literature concerning the relationship between sexual
      functioning and selective serotonin reuptake inhibitors (SSRIs). Reduced sexual
      functioning is a common depressive symptom that typically improves after
      successful antidepressant treatment. On the other hand, sexual dysfunction has
      been observed in a substantial proportion of patients treated with all classes of
      antidepressants. In particular, SSRI use has been shown to be associated with
      sexual dysfunction. A number of pharmacologic interventions have been found to be
      helpful in anecdotal case reports. Unfortunately, the lack of placebo-controlled
      studies in this area limits our ability to draw firm conclusions on the efficacy
      of such interventions. Three classes of drugs have primarily been used to
      counteract sexual side effects of SSRIs: serotonin receptor antagonists, a2
      adrenergic receptor antagonists, and dopaminergic agents. An open trial from our
      group suggests the potential usefulness of oral sildenafil in the treatment of
      antidepressant-associated sexual side effects, but further studies are needed.

PMID- 11964137
TI  - After sildenafil: bridging the gap between pharmacologic treatment and satisfying
      sexual relationships.
AB  - Erectile dysfunction is a prevalent and distressing problem. The availability of
      sildenafil citrate has significantly altered the way in which erectile
      dysfunction is treated. While this medication is extremely effective in restoring
      erectile function, it is often necessary to ensure that the partner is actively
      involved in treatment since many men are in relationships characterized by sexual
      apathy and avoidance as well as relationship conflict. These problems, if left
      untreated, can thwart the transition from sexual abstinence to sexual intimacy.
      Suggestions are offered for evaluating and intervening with men and their
      partners who are planning to resume a sexual life with sildenafil treatment for
      erectile dysfunction.

PMID- 11964138
TI  - Treating sexual dysfunction: psychiatry's role in the age of sildenafil.

PMID- 11964139
TI  - Exploring the relationship between depression and erectile dysfunction in aging
      men.
AB  - Normal sexual function is a biopsychosocial process; sexual dysfunction almost
      always has organic and psychological components and requires multidisciplinary,
      goal-directed evaluation and treatment. Factors such as aging, declining
      testosterone levels, medical illness, certain medications. and comorbid
      depressive illness can contribute to sexual dysfunction. Erectile dysfunction is
      one of the more common male sexual dysfunctions encountered in the clinical
      setting. Comorbidity between erectile dysfunction and depressive illness is high,
      but the causal relationship is unclear. The psychosocial distress that often
      accompanies erectile dysfunction might stimulate the development of depressive
      illness, or, as some data suggest, depression might cause erectile dysfunction.
      This article reviews the literature on the relationship between depression and
      erectile dysfunction, as well as the design of a new study that may provide some
      answers, and concludes that erectile dysfunction is a common, treatable condition
      that may cause or be the result of depression. Recent data suggest that
      sildenafil is an effective treatment for erectile dysfunction in men with
      comorbid depression. Erectile dysfunction should be considered a multifactorial
      condition that may require a multidisciplinary approach to treatment, especially
      when depression is present.

PMID- 11964140
TI  - Activated neutrophils oxidize extracellular proteins of endothelial cells in
      culture: effect of nitric oxide donors.
AB  - Protein oxidation of human umbilical-vein endothelial cells (HUVEC) in culture
      was examined under various conditions of oxidative stress. Extracellular protein
      (ECP) oxidation was assessed by determining dityrosine bond formation, which is
      indicated by the covalent coupling of the membrane-impermeable tyramine
      fluorescein conjugate (TyrFluo) to HUVEC proteins. The acetylated membrane
      permeable form of TyrFluo (acetylTyrFluo) was used for the determination of
      intracellular protein (ICP) oxidation. Oxidative stress was induced by exposing
      the HUVEC to PMA-activated human neutrophils, to a horseradish
      peroxidase/hydrogen peroxide (HRP/H(2)O(2)) system or to H(2)O(2) alone. Coupling
      of the probes was determined by confocal laser scanning microscopy and by Western
      blotting using anti-fluorescein antibody. Diethylamine nitric oxide (DEANO) was
      used to determine the effect of NO on the tyrosyl radical formation in proteins.
      The oxidative burst generated by activated neutrophils for 15 min, resulted in
      inducing dityrosine formation in ECP of HUVEC. Similar results were obtained with
      HRP/H(2)O(2), but H(2)O(2) alone did not have any effect on ECP. In the presence
      of DEANO (0.1 mM or higher), ECP oxidation was almost completely inhibited. This
      indicates that NO may protect endothelial cells against protein oxidation by
      activated neutrophils under pro-inflammatory conditions. Activated neutrophils
      did not oxidize ICP of HUVEC, which strongly suggests that the effect of the
      oxidative burst was restricted to the proteins exposed to the medium.

PMID- 11964141
TI  - Copper uptake is required for pyrrolidine dithiocarbamate-mediated oxidation and
      protein level increase of p53 in cells.
AB  - The p53 tumour-suppressor protein is a transcription factor that activates the
      expression of genes involved in cell cycle arrest, apoptosis and DNA repair. The
      p53 protein is vulnerable to oxidation at cysteine thiol groups. The metal
      chelating dithiocarbamates, pyrrolidine dithiocarbamate (PDTC),
      diethyldithiocarbamate, ethylene(bis)dithiocarbamate and H(2)O(2) were tested for
      their oxidative effects on p53 in cultured human breast cancer cells. Only PDTC
      oxidized p53, although all oxidants tested increased the p53 level. Inductively
      coupled plasma MS analysis indicated that the addition of 60 microM PDTC
      increased the cellular copper concentration by 4-fold, which was the highest
      level of copper accumulated amongst all the oxidants tested.
      Bathocuproinedisulphonic acid, a membrane-impermeable Cu(I) chelator inhibited
      the PDTC-mediated copper accumulation. Bathocuproinedisulphonic acid as well as
      the hydroxyl radical scavenger d-mannitol inhibited the PDTC-dependent increase
      in p53 protein and oxidation. Our results show that a low level of copper
      accumulation in the range of 25-40 microg/g of cellular protein increases the
      steady-state levels of p53. At copper accumulation levels higher than 60 microg/g
      of cellular protein, p53 is oxidized. These results suggest that p53 is
      vulnerable to free radical-mediated oxidation at cysteine residues.

PMID- 11964143
TI  - Ferritin expression modulates cell cycle dynamics and cell responsiveness to H
      ras-induced growth via expansion of the labile iron pool.
AB  - Repression or overexpression of ferritin accelerated or retarded cell cycling
      respectively, via changes in the cellular labile iron pool (LIP). A rise in LIP
      is caused by ferritin repression enhanced growth, induced by H-ras, and reverted
      growth arrest is induced by dominant negative H-ras. The studies indicate that
      repression of ferritin expression provides a mechanism by which certain oncogenes
      lead to cell growth stimulation.

PMID- 11964144
TI  - Characterization of a putative alpha-mannosyltransferase involved in
      phosphatidylinositol trimannoside biosynthesis in Mycobacterium tuberculosis.
AB  - Phosphatidyl-myo-inositol mannosides (PIMs), lipomannan (LM) and
      lipoarabinomannan (LAM) are an important class of bacterial factors termed
      modulins that are found in tuberculosis and leprosy. Although their structures
      are well established, little is known with respect to the molecular aspects of
      the biosynthetic machinery involved in the synthesis of these glycolipids. On the
      basis of sequence similarity to other glycosyltransferases and our previous
      studies defining an alpha-mannosyltransferase from Mycobacterium tuberculosis,
      named PimB [Schaeffer, Khoo, Besra, Chatterjee, Brennan, Belisle and Inamine
      (1999) J. Biol. Chem. 274, 31625-31631], which catalysed the formation of triacyl
      (Ac(3))-PIM(2) (i.e. the dimannoside), we have identified a related gene from M.
      tuberculosis CDC1551, now designated pimC. The use of a cell-free assay
      containing GDP-[(14)C]mannose, amphomycin and membranes from Myobacterium
      smegmatis overexpressing PimC led to the synthesis of a new alkali-labile PIM
      product. Fast-atom-bombardment MS established the identity of the new enzymically
      synthesized product as Ac(3)PIM(3) (i.e. the trimannoside). The results indicate
      that pimC encodes an alpha-mannosyltransferase involved in Ac(3)PIM(3)
      biosynthesis. However, inactivation of pimC in Myobacterium bovis Bacille
      Calmette-Guerin (BCG) did not affect the production of higher PIMs, LM and LAM
      when compared with wild-type M. bovis BCG, suggesting the existence of redundant
      gene(s) or an alternate pathway that may compensate for this PimC deficiency.
      Further analyses, which compared the distribution of pimC in a panel of M.
      tuberculosis strains, revealed that pimC was present in only 22% of the clinical
      isolates examined.

PMID- 11964142
TI  - Endolysosomal proteolysis and its regulation.
AB  - The endolysosomal system comprises a unique environment for proteolysis, which is
      regulated in a manner that apparently does not involve protease inhibitors. The
      system comprises a series of membrane-bound intracellular compartments, within
      which endocytosed material and redundant cellular components are hydrolysed.
      Endocytosed material tends to flow vectorially through the system, proceeding
      through the early endosome, the endosome carrier vesicle, the late endosome and
      the lysosome. Phagocytosis and autophagy provide alternative entry points into
      the system. Late endosomes, lysosome/late endosome hybrid organelles, phagosomes
      and autophagosomes are the principal sites for proteolysis. In each case,
      hydrolytic competence is due to components of the endolysosomal system, i.e.
      proteases, lysosome-associated membrane proteins, H(+)-ATPases and possibly
      cysteine transporters. The view is emerging that lysosomes are organelles for the
      storage of hydrolases, perhaps in an inactivated form. Once a substrate has
      entered a proteolytically competent environment, the rate-limiting proteolytic
      steps are probably effected by cysteine endoproteinases. As these are affected by
      pH and possibly redox potential, they may be regulated by the organelle luminal
      environment. Regulation is probably also affected, among other factors, by
      organelle fusion reactions, whereby the meeting of enzyme and substrate may be
      controlled. Such systems would permit simultaneous regulation of a number of
      unrelated hydrolases.

PMID- 11964146
TI  - Species specificity of O-linked carbohydrate chains of the oviducal mucins in
      amphibians: structural analysis of neutral oligosaccharide alditols released by
      reductive beta-elimination from the egg-jelly coats of Rana clamitans.
AB  - The extracellular matrix (the so-called jelly coat) surrounding amphibian eggs
      mainly comprises highly O-glycosylated proteins. These oviducal mucins have an
      important role in the fertilization process, and their carbohydrate chains are
      remarkably species-specific. Alkaline reductive treatment of the jelly-coat
      material of the frog Rana clamitans led to the release of oligosaccharide
      alditols. The neutral oligosaccharide alditols were fractionated and purified by
      successive chromatographic techniques. The structures of 27 of them, ranging from
      three to sixteen monosaccharides, were established by a combination of NMR
      spectroscopy, methylation analyses and matrix-assisted laser-desorption
      ionization-time of flight MS. Typically, some of the neutral compounds appeared
      to possess the core structure: Gal(beta1-3)[GlcNAc(beta1-6)]Gal(beta1
      3)[GlcNAc(beta1-6)]GalNAc-ol (where GalNAc-ol represents N
      acetylgalactosaminitol). Moreover, a novel type of chain termination,
      characterized by an unusual sequence [Fuc(alpha1-2)Gal(alpha1-3)Gal(alpha1
      4)Gal(beta1-3/4)] was observed. Indeed, the most complex representative structure
      of this series was found to be: Fuc(alpha1-2)Gal(alpha1-3)Gal(alpha1-4)Gal(beta1
      3)[Fuc(alpha1-2)Gal(alpha1-3)Gal(alpha1-4)Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1
      3)[Fuc(alpha1-2)Gal(alpha1-3)Gal(alpha1-4)Gal(beta1-4)GlcNAc(beta1-6)]GalNAc-ol.

PMID- 11964145
TI  - Expression of the two mRNA isoforms of the iron transporter Nramp2/DMTI in mice
      and function of the iron responsive element.
AB  - Nramp2/DMT1 is a transmembrane proton-coupled Fe(2+) transporter. Two different
      mRNAs are generated by alternative splicing; isoform I contains an iron
      responsive element (IRE), whereas isoform II does not. They encode two proteins
      differing at their C-terminal end and by their subcellular localization. IRE
      mediated stabilization of isoform I mRNA is thought to stimulate DMT1 expression
      in response to iron deficiency. We have measured the two mRNAs by real-time
      quantitative PCR in several mouse tissues, in normal conditions or following
      injection of phenylhydrazine, a potent haemolytic agent. Isoform I mRNA is
      expressed in the duodenum and is induced by stimulation of erythropoiesis,
      whereas the non-IRE isoform is mostly induced in erythropoietic spleen.
      Surprisingly, both isoforms are highly expressed in the kidney and are not
      regulated by erythropoiesis. To evaluate the role of the IRE in regulating
      isoform I mRNA stability, in response to variations in cell iron status, several
      constructs were made in pCDNA3 with either a normal or a mutated IRE placed at
      the 3' end of a stable mRNA. These constructs were transfected into HT29 cells
      and mRNAs were analysed after growing cells in the presence or absence of
      exogenous iron. There was no difference in the level of expression of the
      different messages, suggesting that the IRE does not regulate stability of
      isoform I mRNA. The half-life of the endogenous IRE-mRNA was also measured
      following actinomycin D addition in iron- or desferrioxamine-treated cells. Decay
      of the mRNA was very similar in both conditions. These results suggest that
      additional transcriptional regulations at the promoter level, or iron-dependent
      regulation of alternative splicing are likely to participate in the induction of
      isoform I mRNA by iron deficiency.

PMID- 11964147
TI  - Association of thrombospondin-1 with the actin cytoskeleton of human thrombin
      activated platelets through an alphaIIbbeta3- or CD36-independent mechanism.
AB  - Thrombospondin-1 (TSP-1) is an adhesive glycoprotein which, when secreted from
      alpha-granules of activated platelets, can bind to the cell surface and
      participate in platelet aggregate formation. In this study, we show that thrombin
      activation leads to the rapid and specific association of a large amount of
      secreted alpha-granular TSP-1 with the actin cytoskeleton. This cytoskeletal
      association of TSP-1 was correlated with platelet secretion, but not aggregation,
      and was inhibited by cytochalasin D, an inhibitor of actin polymerization.
      Association of TSP-1 with the actin cytoskeleton was mediated by membrane
      receptors, as shown by using MAII, a TSP-1-specific monoclonal antibody that
      inhibited both TSP-1 surface binding to activated platelets and cytoskeletal
      association. TSP-1 and its potential membrane receptors, e.g. alphaIIbbeta3
      integrin, CD36 and CD47, concomitantly associated with the actin cytoskeleton.
      However, studies on platelets from a patient with type I Glanzmann's
      thrombasthenia lacking alphaIIbbeta3 and another with barely detectable CD36
      showed normal TSP-1 surface expression and association with the actin
      cytoskeleton. Likewise, no involvement of CD47 in TSP-1 association with the
      actin cytoskeleton could be inferred from experiments with control platelets
      using the function-blocking anti-CD47 antibody B6H12. Finally, assembly of
      signalling complexes, as observed through translocation of tyrosine
      phosphorylated proteins and kinases to the actin cytoskeleton, was found to occur
      in concert with cytoskeletal association of TSP-1, in control platelets as well
      as in thrombasthenic and CD36-deficient platelets. Our results imply a role for
      the actin cytoskeleton in the membrane-surface expression process of TSP-1
      molecules and suggest a possible coupling of TSP-1 receptors to signalling events
      occurring independently of alphaIIbbeta3 or CD36. These results provide new
      insights into the link between surface-bound TSP-1 and the contractile actin
      microfilament system which may promote platelet aggregate cohesion.

PMID- 11964149
TI  - Modulation of the electrostatic charge at the active site of foot-and-mouth
      disease-virus leader proteinase, an unusual papain-like enzyme.
AB  - The leader proteinase (L(pro)) of foot-and-mouth-disease virus is an unusual
      papain-like cysteine proteinase. Synthesized without an N-terminal pro precursor
      region, it frees itself from the growing polypeptide chain by cleavage at its own
      C-terminus. It also possesses a unique electrostatic environment around the
      active site, essentially due to Asp(163), which orients the catalytic histidine
      residue, and Asp(164); the equivalent residues in papain are Asn(175) and
      Ser(176). The importance of these residues for L(pro) activity was examined by
      site-directed mutagenesis. Replacement of Asp(163) with asparagine reduced
      activity by five-fold towards a hexapeptide substrate and slightly delayed self
      processing when expressed in rabbit reticulocyte lysates. However, no effect on
      the cleavage of the only known cellular substrate of L(pro), eukaryotic
      initiation factor 4GI (eIF4GI), was observed. In contrast, replacement of
      Asp(164) by either alanine, asparagine or lysine abrogated activity towards the
      hexapeptide. Furthermore, in all cases, the onset of both self-processing and
      eIF4GI cleavage were significantly delayed; the reaction rates were also
      diminished compared with those of the wild-type enzyme. The alanine-substituted
      enzyme was least affected, followed by those substituted with asparagine and
      lysine. The double mutant protein in which both aspartate residues were replaced
      by asparagine was most severely affected; it failed to complete either self
      processing or eIF4GI cleavage within 3 h, compared with the 8 min required by the
      wild-type enzyme. Hence, we propose that the electrostatic charge of Asp(164),
      and to a lesser extent that of Asp(163), is extremely important for L(pro) to
      attain full activity upon synthesis.

PMID- 11964148
TI  - Sensitive and real-time determination of H2O2 release from intact peroxisomes.
AB  - Peroxisomes are essential and ubiquitous cell organelles having a key role in
      mammalian lipid and oxygen metabolism. The presence of flavine oxidases makes
      them an important intracellular source of H(2)O(2): an obligate product of
      peroxisomal redox reactions and a key reactive oxygen species. Peroxisomes
      proliferate in response to external signals triggered by peroxisome-proliferator
      activated receptor signalling pathways. Peroxisome-derived oxidative stress as a
      consequence of this proliferation is increasingly recognized to participate in
      pathologies ranging from carcinogenesis in rodents to alcoholic and non-alcoholic
      steatosis hepatitis in humans. To date, no sensitive approach exists to record
      H(2)O(2) turnover of peroxisomes in real time. Here, we introduce a sensitive
      chemiluminescence method that allows the monitoring of H(2)O(2) generation and
      degradation in real time in suspensions of intact peroxisomes. Importantly,
      removal, as well as release of, H(2)O(2) can be assessed at nanomolar, non-toxic
      concentrations in the same sample. Owing to the kinetic properties of catalase
      and oxidases, H(2)O(2) forms fast steady-state concentrations in the presence of
      various peroxisomal substrates. Substrate screening suggests that urate,
      glycolate and activated fatty acids are the most important sources for H(2)O(2)
      in rodents. Kinetic studies imply further that peroxisomes contribute
      significantly to the beta-oxidation of medium-chain fatty acids, in addition to
      their essential role in the breakdown of long and very long ones. These
      observations establish a direct quantitative release of H(2)O(2) from intact
      peroxisomes. The experimental approach offers new possibilities for functionally
      studying H(2)O(2) metabolism, substrate transport and turnover in peroxisomes of
      eukaryotic cells.

PMID- 11964150
TI  - A novel TATA-box-binding factor from the silk glands of the mulberry silkworm,
      Bombyx mori.
AB  - The presence of one or more TATATAA motifs in the flanking sequences of
      individual members of a multi-gene tRNA(Gly)(1) family from the mulberry
      silkworm, Bombyx mori, negatively modulated the transcription of the gene copies.
      Characterization of proteins from posterior silk gland nuclear extracts, binding
      to the TATATAA motif, identified a novel 43 kD protein, designated here as P43
      TATA-box-binding factor (TBF). The protein was purified to homogeneity. P43 TBF
      binding was highly sequence-specific and showed a 100-fold-higher affinity for
      binding than the TATA-box-binding protein (TBP). The protein also showed binding
      to the TATAAA sequence of the actin5C promoter. P43 TBF inhibited transcription
      of all the tRNA genes examined, as well as RNA polymerase II transcription from
      the actin5C promoter. The amino acid sequence of eleven peptides generated from
      P43 TBF did not share homology with proteins that bind the TATA box, such as TBP,
      TRF (TBP-related factor) or TLFs (TBP-like factors) reported from other sources.
      Inhibition of transcription of tRNA genes by P43 TBF could not be reversed by
      TBP. The inhibitory effect appeared to be exerted through sequestration of the
      associated transcription factors.

PMID- 11964151
TI  - Gal3p and Gal1p interact with the transcriptional repressor Gal80p to form a
      complex of 1:1 stoichiometry.
AB  - The genes encoding the enzymes required for galactose metabolism in Saccharomyces
      cerevisiae are controlled at the level of transcription by a genetic switch
      consisting of three proteins: a transcriptional activator, Gal4p; a
      transcriptional repressor, Gal80p; and a ligand sensor, Gal3p. The switch is
      turned on in the presence of two small molecule ligands, galactose and ATP. Gal3p
      shows a high degree of sequence identity with Gal1p, the yeast galactokinase. We
      have mapped the interaction between Gal80p and Gal3p, which only occurs in the
      presence of both ligands, using protease protection experiments and have shown
      that this involves amino acid residue 331 of Gal80p. Gel-filtration experiments
      indicate that Gal3p, or the galactokinase Gal1p, interact directly with Gal80p to
      form a complex with 1:1 stoichiometry.

PMID- 11964152
TI  - Alteration of pore properties of Escherichia coli OmpF induced by mutation of key
      residues in anti-loop 3 region.
AB  - The Escherichia coli OmpF pore is governed by an internal constriction consisting
      of the negatively charged loop 3 folded into the lumen and the positively charged
      barrel wall located on the opposite side across the pore, 'anti-loop 3'. To
      investigate the role of anti-loop 3 in solute diffusion, four site-directed
      mutations, K16A, K16D, R132A and R132D, were introduced into this eyelet region.
      The mutant porins were expressed efficiently and inserted into the outer
      membrane, and the thermal stabilities of the resulting trimers were determined.
      Diffusion of cefepime, a recently developed cephalosporin, was analysed in vivo.
      In vitro studies were performed on purified porins reconstituted in planar lipid
      bilayers to measure conductance, selectivity and voltage closure, as well as in
      liposomes for patch-clamp and sugar-swelling assays. All substitutions modified
      the ion-channel parameters, and minor conformational changes in the OmpF eyelet
      region were predicted from modelling studies. Our data show that Lys-16, and to a
      lesser extent Arg-132, are involved in voltage-gating and pore selectivity via
      their side-chain charges. Substitution K16D, which causes a severe decrease in
      critical voltage (V(c)), may generate a channel susceptible to membrane
      potential, which perturbs cefepime diffusion. These results suggest that the Lys
      16 residue plays an important role in the process of diffusion through the OmpF
      lumen.

PMID- 11964153
TI  - Stimulation of erythroleukaemia cell differentiation by extracellular high
      mobility group-box protein 1 is independent of the receptor for advanced
      glycation end-products.
AB  - In several cell types the binding of extracellular high-mobility group-box
      protein 1 (HMGB1) with the receptor for advanced glycation end-products (RAGE)
      induces cytoskeletal reorganization and cell motility. To establish whether RAGE
      is also involved in murine erythroleukaemia (MEL) cell differentiation stimulated
      by HMGB1, we have demonstrated that these cells express a 51 kDa protein
      identified as RAGE, and then we have produced stable transfectants overexpressing
      wild-type (wt) RAGE or a dominant negative (dn) RAGE mutant lacking the
      cytoplasmic domain to analyse the differentiation process in these cells. Several
      experimental findings indicated that RAGE was not involved in the MEL cell
      differentiation programme. This was also supported by the identical stimulatory
      effect exerted by HMGB1 on both wt- or dn-RAGE transfectants. We have also
      observed that HMGB1 binds a 65 kDa protein on the surface of MEL cells,
      supporting the hypothesis that alternative targets of HMGB1 are expressed on the
      MEL cell membrane and may be involved as mediators of its signalling.

PMID- 11964154
TI  - Regulation of novel protein kinase C epsilon by phosphorylation.
AB  - The activity and intracellular localization of protein kinase C (PKC) family
      members are controlled by phosphorylation at three highly conserved sites in the
      catalytic kinase domain. In the case of the novel PKCepsilon isoform, these are
      Thr(566) in the activation loop, Thr(710) in the turn motif and Ser(729) in the C
      terminal hydrophobic motif. In the present study, we analysed the contribution of
      the phosphoinositide-dependent kinase 1 (PDK-1) and PKCepsilon kinase activity in
      controlling the phosphorylation of Thr(566) and Ser(729). In NIH 3T3 fibroblasts,
      PKCepsilon migrated as a single band, and stimulation with platelet-derived
      growth factor resulted in the appearance of a second band with a slower
      electrophoretic mobility, concomitant with an increase in phosphorylation of
      Thr(566) and Ser(729). Cells transfected with an active PDK-1 allele also
      resulted in increased PKCepsilon Thr(566) and Ser(729) phosphorylation, whereas
      an active myristoylated PKCepsilon mutant was constitutively phosphorylated at
      these sites. Protein kinase-inactive mutants of PKCepsilon were not
      phosphorylated at Ser(729) in cells, and phosphorylation of this site leads to
      dephosphorylation of the activation-loop Thr(566), an effect which can be
      reversed with either okadaic acid or co-transfection with active PDK-1. In vitro,
      PDK-1 catalysed the phosphorylation of purified PKCepsilon in the presence of
      mixed micelles containing either diacylglycerol or PtdIns(3,4,5)P(3), concomitant
      with an increase in Ser(729) phosphorylation. These studies reveal that the
      mechanism of phosphorylation of a novel PKC is the same as that for conventional
      PKCs: PDK-1 phosphorylation of the activation loop triggers autophosphorylation
      of the hydrophobic motif. However, the regulation of this phosphorylation is
      different for novel and conventional PKCs. Specifically, the phosphorylation of
      novel PKCs is regulated rather than constitutive.

PMID- 11964155
TI  - Bid induces cytochrome c-impermeable Bax channels in liposomes.
AB  - Bax is a proapoptotic member of the Bcl-2 family of proteins. The Bax protein is
      dormant in the cytosol of normal cells and is activated upon induction of
      apoptosis. In apoptotic cells, Bax gets translocated to mitochondria, inserts
      into the outer membrane, oligomerizes and triggers the release of cytochrome c,
      possibly by channel formation. The BH3 domain-only protein Bid induces a
      conformational change in Bax before its insertion into the outer membrane. The
      mechanism by which Bid promotes Bax activation is not understood, and whether Bid
      is the only protein required for Bax activation is unclear. Here we report that
      recombinant full-length Bax (Bax(FL)) does not form channels in lipid bilayers
      when purified as a monomer. In contrast, in the presence of Bid cut with caspase
      8 (cut Bid), Bax forms ionic channels in liposomes and planar bilayers. This
      channel-forming activity requires an interaction between cut Bid and Bax, and is
      inhibited by Bcl-x(L). Moreover, in the absence of the putative transmembrane C
      terminal domain, Bax does not form ionic channels in the presence of cut Bid. Cut
      Bid does not induce Bax oligomerization in liposomes and the Bax channels formed
      in the presence of cut Bid are not large enough to permeabilize vesicles to
      cytochrome c. In conclusion, our results suggest that monomeric Bax(FL) can form
      channels only in the presence of cut Bid. Cut Bid by itself is unable to induce
      Bax oligomerization in lipid membranes. It is suggested that another factor that
      might be present in mitochondria is required for Bax oligomerization.

PMID- 11964156
TI  - The solution structure of ribosomal protein L18 from Thermus thermophilus reveals
      a conserved RNA-binding fold.
AB  - We have determined the solution structure of ribosomal protein L18 from Thermus
      thermophilus. L18 is a 12.5 kDa protein of the large subunit of the ribosome and
      binds to both 5 S and 23 S rRNA. In the uncomplexed state L18 folds to a mixed
      alpha/beta globular structure with a long disordered N-terminal region. We
      compared our high-resolution structure with RNA-complexed L18 from Haloarcula
      marismortui and T. thermophilus to examine RNA-induced as well as species
      dependent structural differences. We also identified T. thermophilus S11 as a
      structural homologue and found that the structures of the RNA-recognition sites
      are conserved. Important features, for instance a bulge in the RNA-contacting
      beta-sheet, are conserved in both proteins. We suggest that the L18 fold
      recognizes a specific RNA motif and that the resulting RNA-protein-recognition
      module is tolerant to variations in sequence.

PMID- 11964157
TI  - Type IIalpha phosphatidylinositol phosphate kinase associates with the plasma
      membrane via interaction with type I isoforms.
AB  - The phosphatidylinositol phosphate kinases (PIPkins) are a family of enzymes
      involved in regulating levels of several functionally important inositol
      phospholipids within cells. The PIPkin family is subdivided into three on the
      basis of substrate specificity, each subtype presumably regulating levels of
      different subsets of the inositol lipids. The physiological function of the type
      II isoforms, which exhibit a preference for phosphatidylinositol 5-phosphate, a
      lipid about which very little is known, is particularly poorly understood. In the
      present study, we demonstrate interaction between, and co-immunoprecipitation of,
      type IIalpha PIPkin with the related, but biochemically and immunologically
      distinct, type I PIPkin isoforms. Type IIalpha PIPkin interacts with all three
      known type I PIPkins (alpha, beta and gamma), and in each case co-expression of
      the type I isoform with type IIalpha results in recruitment of the latter from
      the cytosol to the plasma membrane of the cell. This change in subcellular
      localization could result in improved access of the type IIalpha PIPkin to its
      lipid substrates.

PMID- 11964158
TI  - Spectroscopic characterization of mutations at the Phe41 position in the distal
      haem pocket of horseradish peroxidase C: structural and functional consequences.
AB  - Three mutants of horseradish peroxidase isoenzyme C (HRPC) have been constructed
      in which the conserved distal aromatic residue Phe(41) has been substituted by
      Trp, Val or Ala and the properties of the mutant proteins have been compared with
      that of the wild-type. The ferric and ferrous states have been studied by
      resonance Raman, electronic absorption and Fourier-transform infrared
      spectroscopies, together with their respective fluoride and CO complexes as
      probes for the integrity of the distal haem-pocket hydrogen-bonding network. The
      catalytic properties of the mutants, most notably the HRPC-mutant Phe(41)-->Trp
      (F41W) variant, were also affected. Structural modelling suggests that the bulky
      indole group of the F41W mutant blocks the distal cavity, inhibiting the binding
      of fluoride and CO to the haem iron, severely impairing the reaction of the
      enzyme with H(2)O(2) to form Compound I. Substitution with the smaller side-chain
      residues Val or Ala resulted in a 2-fold increase in the affinity of the mutants
      for the aromatic donor benzhydroxamic acid (BHA) compared with the wild-type,
      whereas the sterically hindered F41W mutant was not able to bind BHA at all. All
      the mutations studied increased the amount of a ferric six-coordinate aquo-high
      spin species. On the other hand, the similarity in the Fe-Im stretching
      frequencies of the mutants and wild-type protein suggests that the distal haem
      pocket mutations do not cause any substantive changes on the proximal side of the
      haem. Spectra of the HRPC mutant Phe(41)-->Ala-CO and the HRPC mutant Phe(41)-
      >Val-CO complexes strongly suggested a weakening of the interaction between CO
      and Arg(38) due to a secondary rearrangement of the haem relative to helix B. The
      effects observed for these HRP mutants were somewhat different from those noted
      recently for the analogous Coprinus cinereus peroxidase (CIP) mutants,
      particularly the Trp mutant. These differences can be reconciled in part as being
      due to the smaller size of the distal cavity of HRP compared with that of CIP.

PMID- 11964159
TI  - Enzymic degradation of plasma arginine using arginine deiminase inhibits nitric
      oxide production and protects mice from the lethal effects of tumour necrosis
      factor alpha and endotoxin.
AB  - Septic shock is mediated in part by nitric oxide (NO) and tumour necrosis factor
      alpha (TNFalpha). NO is synthesized primarily from extracellular arginine. We
      tested the ability of an arginine-degrading enzyme to inhibit NO production in
      mice and to protect mice from the hypotension and lethality that occur after the
      administration of TNFalpha or endotoxin. Treatment of BALB/c mice with arginine
      deiminase (ADI) formulated with succinimidyl succinimide polyethylene glycol of
      M(r) 20000 (ADI-SS PEG(20000)) eliminated all measurable plasma arginine (from
      normal levels of approximately 155 microM arginine to 2 microM). In addition, ADI
      SS PEG(20000) also inhibited the production of NO, as quantified by plasma
      nitrate+nitrite. Treatment of mice with TNFalpha or endotoxin resulted in a dose
      dependent increase in NO production and lethality. Pretreatment of mice with ADI
      SS PEG(20000) resulted in increased resistance to the lethal effects of TNFalpha
      and endotoxin. These observations are consistent with NO production resulting, to
      some extent, from the metabolism of extracellular arginine. The toxic effects of
      TNFalpha and endotoxin may be partially inhibited by enzymic degradation of
      plasma arginine by ADI-SS PEG(20000). Interestingly, pretreatment with ADI-SS
      PEG(20000) did not inhibit the anti-tumour activity of TNFalpha in vitro or in
      vivo. This treatment may allow greater amounts of TNFalpha, as well as other
      cytokines, to be administered while abrogating side effects such as hypotension
      and death.

PMID- 11964161
TI  - Identification of Ca2+-dependent binding partners for the neuronal calcium sensor
      protein neurocalcin delta: interaction with actin, clathrin and tubulin.
AB  - The neuronal calcium sensors are a family of EF-hand-containing Ca(2+)-binding
      proteins expressed predominantly in retinal photoreceptors and neurons. One of
      the family members is neurocalcin delta, the function of which is unknown. As an
      approach to elucidating the protein interactions made by neurocalcin delta, we
      have identified brain cytosolic proteins that bind to neurocalcin delta in a
      Ca(2+)-dependent manner. We used immobilized recombinant myristoylated
      neurocalcin delta combined with protein identification using MS. We demonstrate a
      specific interaction with clathrin heavy chain, alpha- and beta-tubulin, and
      actin. These interactions were dependent upon myristoylation of neurocalcin delta
      indicating that the N-terminal myristoyl group may be important for protein
      protein interactions in addition to membrane association. Direct binding of
      neurocalcin delta to clathrin, tubulin and actin was confirmed using an overlay
      assay. These interactions were also demonstrated for endogenous neurocalcin delta
      by co-immunoprecipitation from rat brain cytosol. When expressed in HeLa cells,
      neurocalcin delta was cytosolic at resting Ca(2+) levels but translocated to
      membranes, including a perinuclear compartment (trans-Golgi network) where it co
      localized with clathrin, following Ca(2+) elevation. These data suggest the
      possibility that neurocalcin delta functions in the control of clathrin-coated
      vesicle traffic.

PMID- 11964160
TI  - The mouse Muc5b mucin gene: cDNA and genomic structures, chromosomal localization
      and expression.
AB  - We report here the isolation and characterization of the mouse Muc5b mucin gene
      (mMuc5b). We determined its complete cDNA sequence, its genomic organization, and
      chromosomal localization. Moreover, we analyzed the expression of this gene by
      reverse-transcription PCR and in situ hybridization. The structure of the gene
      was determined from a genomic cosmid clone that encompasses the entire mMuc5b
      gene, including the 5'-flanking region. The mMuc5b gene spans approximately 36 kb
      and contains 49 exons. It is located on mouse distal chromosome 7. mMuc5b encodes
      at least two transcripts by alternative splicing of the second exon, the longest
      one being 14.9 kb in length. The deduced peptide contains 4782 amino acids. Its
      central region can be subdivided into 10 imperfect repeats, each composed of a
      cysteine-rich domain followed by a threonine, serine, and proline-rich mucin-type
      domain. It is flanked by cysteine-rich domains similar to cysteine-rich domains
      of pre-pro-von Willebrand factor. Comparison with its human homologue MUC5B
      revealed common features including high sequence similarities in the 5' and 3'
      regions, and the conservation of the genomic organization. In contrast, mMuc5b
      differs from its human homologue, since no highly tandemly repeated sequences
      could be identified within its central region. mMuc5b is expressed mainly in
      laryngeal mucous glands, and at a lesser extend in stomach and duodenum.

PMID- 11964162
TI  - Chicken avidin-related proteins show altered biotin-binding and physico-chemical
      properties as compared with avidin.
AB  - Chicken avidin and bacterial streptavidin are proteins familiar from their use in
      various (strept)avidin-biotin technological applications. Avidin binds the
      vitamin biotin with the highest affinity known for non-covalent interactions
      found in nature. The gene encoding avidin (AVD) has homologues in chicken, named
      avidin-related genes (AVRs). In the present study we used the AVR genes to
      produce recombinant AVR proteins (AVRs 1, 2, 3, 4/5, 6 and 7) in insect cell
      cultures and characterized their biotin-binding affinity and biochemical
      properties. Amino acid sequence analysis and molecular modelling were also used
      to predict and explain the properties of the AVRs. We found that the AVR proteins
      are very similar to avidin, both structurally and functionally. Despite the
      numerous amino acid substitutions in the subunit interface regions, the AVRs form
      extremely stable tetramers similar to those of avidin. Differences were found in
      some physico-chemical properties of the AVRs as compared with avidin, including
      lowered pI, increased glycosylation and, most notably, reversible biotin binding
      for two AVRs (AVR1 and AVR2). Molecular modelling showed how the replacement
      Lys(111)-->isoleucine in AVR2 alters the shape of the biotin-binding pocket and
      thus results in reversible binding. Both modelling and biochemical analyses
      showed that disulphide bonds can form and link monomers in AVR4/5, a property not
      found in avidin. These, together with the other properties of the AVRs described
      in the present paper, may offer advantages over avidin and streptavidin, making
      the AVRs applicable for improved avidin-biotin technological applications.

PMID- 11964163
TI  - Overloading and removal of N-glycosylation targets on human acetylcholinesterase:
      effects on glycan composition and circulatory residence time.
AB  - Optimization of post-translational modifications was shown to affect the ability
      of recombinant human acetylcholinesterase (rHuAChE) produced in HEK-293 cells to
      be retained in the circulation for prolonged periods of time [Kronman, Velan,
      Marcus, Ordentlich, Reuveny and Shafferman (1995) Biochem. J. 311, 959-967;
      Chitlaru, Kronman, Zeevi, Kam, Harel, Ordentlich, Velan and Shafferman (1998)
      Biochem. J. 336, 647-658; Chitlaru, Kronman, Velan and Shafferman (2001) Biochem.
      J. 354, 613-625]. To evaluate the possible contribution of the number of appended
      N-glycans in determining the pharmacokinetic behaviour of AChE, a series of
      sixteen recombinant human AChE glycoforms, differing in their number of appended
      N-glycans (2, 3, 4 or 5 glycans), state of assembly (dimeric or tetrameric) and
      terminal glycan sialylation (partially or fully sialylated) were generated.
      Extensive structural analysis of N-glycans demonstrated that the various glycan
      types associated with all the different rHuAChE glycoforms are essentially
      similar both in structure and abundance, and that production of the various
      glycoforms in the sialyltransferase-overexpressing 293ST-2D6 cell line resulted
      in the generation of enzyme species that carry glycans sialylated to the same
      extent. Pharmacokinetic profiling of the rHuAChE glycoforms in their fully
      tetramerized and sialylated state clearly demonstrated that circulatory longevity
      correlated directly with the number of attached N-glycans (mean residence times
      for rHuAChE glycoforms harbouring 2, 3, and 4 glycans=200, 740, and 1055 min
      respectively). This study provides evidence that glycan loading, together with N
      glycan terminal processing and enzyme subunit oligomerization, operate in a
      hierarchical and concerted manner in determining the pharmacokinetic
      characteristics of AChE.

PMID- 11964164
TI  - The Drosophila odz/ten-m gene encodes a type I, multiply cleaved heterodimeric
      transmembrane protein.
AB  - The product of the Drosophila melanogaster odd Oz (odz)/Tenascin-major (ten-m)
      pair-rule gene consists of eight epidermal growth factor (EGF)-like repeats
      followed by a novel 1800 amino acid polypeptide stretch unique to proteins of the
      Odz/Ten-m family. The structure and membrane orientation of this large enigmatic
      protein was characterized by raising and employing antibodies directed against
      discrete Odz polypeptide regions. Protein-modifying reagents impermeable to the
      plasma membrane were used in concert with the battery of antibodies to
      demonstrate that Odz is a type I transmembrane protein with the vast C-terminal
      portion in the intracellular space, and with the EGF repeats deployed
      extracellularly. The polypeptide was shown to undergo multiple cleavages at
      discrete intracellular and extracellular sites, and its extreme C-terminus was
      shown to undergo either processing at a very large number of sites or programmed
      degradation. The polypeptide is presented at the cell surface with additional
      post-translational modifications, and as two subunits of previously cleaved Odz
      joined by cysteine disulphide bridges maintaining their association. The model
      derived for the Odz protein is discussed in light of other models proposed for
      proteins of the Odz/Ten-m family, and in terms of functional implications.

PMID- 11964165
TI  - Metabolic labelling of membrane microdomains/rafts in Jurkat cells indicates the
      presence of glycerophospholipids implicated in signal transduction by the CD3 T
      cell receptor.
AB  - Cell membranes contain sphingolipids and cholesterol, which cluster together in
      distinct domains called rafts. The outer-membrane leaflet of these peculiar
      membrane domains contains glycosylphosphatidylinositol-anchored proteins, while
      the inner leaflet contains proteins implicated in signalling, such as the
      acylated protein kinase p56(lck) and the palmitoylated adaptator LAT (linker for
      activation of T-cells). We present here an approach to study the lipid
      composition of rafts and its change upon T-cell activation. Our method is based
      on metabolic labelling of Jurkat T-cells with different precursors of
      glycerophospholipid synthesis, including glycerol and fatty acids with different
      lengths and degrees of saturation as well as phospholipid polar head groups. The
      results obtained indicate that lipid rafts isolated by the use of sucrose density
      gradient centrifugation after Triton X-100 extraction in the cold, besides
      sphingolipids and cholesterol, contain unambiguously all classes of
      glycerophospholipids: phosphatidylserine, phosphatidylinositol,
      phosphatidylethanolamine and phosphatidylcholine. Fatty acid labelling shows that
      lipid rafts are labelled preferentially with saturated fatty acids while the rest
      of the plasma membrane incorporates mostly long-chained polyunsaturated fatty
      acids. To see whether the raft composition as measured by metabolic labelling of
      phospholipids is involved in T-cell activation, we investigated the production of
      sn-1,2-diacylglycerol (DAG) in CD3-activated cells. DAG production occurs within
      rafts, confirming previous demonstration of protein kinase C translocation into
      membrane microdomains. Our data demonstrate that raft disorganization by methyl
      beta-cyclodextrin impairs both CD3-induced DAG production and changes in
      cytosolic Ca(2+) concentration. These lines of evidence support the conclusion
      that the major events in T-cell activation occur within or due to lipid rafts.

PMID- 11964167
TI  - Interaction of the 1alpha,25-dihydroxyvitamin D3 receptor at the distal promoter
      region of the bone-specific osteocalcin gene requires nucleosomal remodelling.
AB  - 1alpha,25-Dihydroxyvitamin D3-mediated transcriptional control of the bone
      specific osteocalcin (OC) gene requires the integration of regulatory signals at
      the vitamin D-responsive element (VDRE) and flanking tissue-specific sequences.
      The 1alpha,25-dihydroxyvitamin D3 receptor (VDR) is a member of the nuclear
      receptor superfamily and forms a heterodimeric complex with the receptor for 9
      cis retinoic acid (RXR) that binds to the VDRE sequence. We have demonstrated
      previously that changes in chromatin structure at the VDRE region of the rat OC
      gene promoter accompany transcriptional enhancement in vivo, suggesting a
      requirement for chromatin remodelling. Here we show that the VDRE in the distal
      region of the OC gene promoter is refractory to binding of the VDR-RXR complex
      when organized in a nucleosomal context. Addition of the ligand 1alpha,25
      dihydroxyvitamin D3 or the presence of other transcription factors, such as YY1
      and Runx/Cbfa (core-binding factor alpha), which also bind to sequences partially
      overlapping or near the VDRE, is not sufficient to render the VDRE accessible.
      Thus the VDR-RXR, unlike other steroid receptors, such as glucocorticoid
      receptor, progesterone receptor and thyroid receptor, is unable to bind its
      target sequence within a nucleosomal context. Taken together these results
      demonstrate that nucleosomal remodelling is required for in vivo occupancy of
      binding sites in the distal region of the OC gene promoter by the regulatory
      factors responsible for 1alpha,25-dihydroxyvitamin D3-dependent enhancement of
      transcription.

PMID- 11964166
TI  - Subcellular localization of phosphatidylinositol 4,5-bisphosphate using the
      pleckstrin homology domain of phospholipase C delta1.
AB  - Ptd(4,5)P(2) is thought to promote and organize a wide range of cellular
      functions, including vesicular membrane traffic and cytoskeletal dynamics, by
      recruiting functional protein complexes to restricted locations in cellular
      membranes. However, little is known about the distribution of PtdIns(4,5)P(2) in
      the cell at high resolution. We have used the pleckstrin homology (PH) domain of
      phospholipase delta(1) (PLCdelta(1)), narrowly specific for PtdIns(4,5)P(2), to
      map the distribution of the lipid in astrocytoma and A431 cells. We applied the
      glutathione S-transferase-tagged PLCdelta(1) PH domain (PLCdelta(1)PH-GST) in an
      on-section labelling approach which avoids transfection procedures. Here we
      demonstrate PtdIns(4,5)P(2) labelling in the plasma membrane, and also in
      intracellular membranes, including Golgi (mainly stack), endosomes and
      endoplasmic reticulum, as well as in electron-dense structures within the
      nucleus. At the plasma membrane, labelling was more concentrated over
      lamellipodia, but not in caveolae, which contained less than 10% of the total
      cell-surface labelling. A dramatic decrease in signal over labelled compartments
      was observed on preincubation with the cognate headgroup [Ins(1,4,5)P(3)], and
      plasma-membrane labelling was substantially decreased after stimulation with
      thrombin-receptor-activating peptide (SFLLRN in the one-letter amino acid code),
      a treatment which markedly diminishes PtdIns(4,5)P(2) levels. Thus we have
      developed a highly selective method for mapping the PtdIns(4,5)P(2) distribution
      within cells at high resolution, and our data provide direct evidence for this
      lipid at key functional locations.

PMID- 11964168
TI  - A continuous-wave electron-nuclear double resonance (X-band) study of the Cu2+
      sites of particulate methane mono-oxygenase of Methylococcus capsulatus (strain
      M) in membrane and pure dopamine beta-mono-oxygenase of the adrenal medulla.
AB  - All methanotrophic bacteria express a membrane-bound (particulate) methane mono
      oxygenase (pMMO). In the present study, we have investigated pMMO in membrane
      fragments from Methylococcus capsulatus (strain M). pMMO contains a typical type
      2 Cu(2+) centre with the following EPR parameters: g(z) 2.24, g(x,y) 2.06,
      A(Cu)(z) 19.0 mT and A(Cu)(x,y) 1.0 mT. Simulation of the Cu(2+) spectrum yielded
      a best match by using four equivalent nitrogens (A(N)=1.5 mT, 42 MHz). Incubation
      with ferricyanide neither changed nor increased the amount of EPR-active Cu(2+),
      in contrast with other reports. The EPR visible copper seems not to be part of
      any cluster, as judged from the microwave power saturation behaviour. Continuous
      wave electron-nuclear double resonance (CW ENDOR; 9.4 GHz, 5-20 K) experiments at
      g( perpendicular) of the Cu(II) spectrum show a weak coupling to protons with an
      A(H) of 2.9 MHz that corresponds to a distance of 3.8 A (1 A identical with 0.1
      nm), assuming that it is a purely dipolar coupling. Incubation in (2)H(2)O leads
      to a significant decrease in these (1)H-ENDOR intensities, showing that these
      protons are exchangeable. This result strongly suggests that the EPR visible
      copper site of pMMO is accessible to solvent, which was confirmed by the
      chelation of the Cu(2+) by diethyldithiocarbamic acid. The (1)H and (14)N
      hyperfine coupling constants confirm a histidine ligation of the EPR visible
      copper site in pMMO. The hyperfine structure in the ENDOR or EPR spectra of pMMO
      is not influenced by the inhibitors azide, cyanide or ammonia, indicating that
      they do not bind to the EPR visible copper. We compared pMMO with the type-2
      Cu(2+) enzyme, dopamine beta-mono-oxygenase (DbetaM). For DbetaM, it is assumed
      that the copper site is solvent-accessible. CW ENDOR shows similar weakly coupled
      and (2)H(2)O-exchangeable protons (2.9 MHz), as observed in pMMO, as well as the
      strongly coupled nitrogens (40 MHz) from the co-ordinating N of the histidines in
      DbetaM. In conclusion, the resting EPR visible Cu in pMMO is not part of a
      trinuclear cluster, as has been suggested previously.

PMID- 11964169
TI  - Mutational analysis of the two zinc-binding sites of the Bacillus cereus 569/H/9
      metallo-beta-lactamase.
AB  - The metallo-beta-lactamase BcII from Bacillus cereus 569/H/9 possesses a
      binuclear zinc centre. The mono-zinc form of the enzyme displays an appreciably
      high activity, although full efficiency is observed for the di-zinc enzyme. In an
      attempt to assign the involvement of the different zinc ligands in the catalytic
      properties of BcII, individual substitutions of selected amino acids were
      generated. With the exception of His(116)-->Ser (H116S), C221A and C221S, the
      mono- and di-zinc forms of all the other mutants were poorly active. The activity
      of H116S decreases by a factor of 10 when compared with the wild type. The
      catalytic efficiency of C221A and C221S was zinc-dependent. The mono-zinc forms
      of these mutants exhibited a low activity, whereas the catalytic efficiency of
      their respective di-zinc forms was comparable with that of the wild type.
      Surprisingly, the zinc contents of the mutants and the wild-type BcII were
      similar. These data suggest that the affinity of the beta-lactamase for the metal
      was not affected by the substitution of the ligand. The pH-dependence of the
      H196S catalytic efficiency indicates that the zinc ions participate in the
      hydrolysis of the beta-lactam ring by acting as a Lewis acid. The zinc ions
      activate the catalytic water molecule, but also polarize the carbonyl bond of the
      beta-lactam ring and stabilize the development of a negative charge on the
      carbonyl oxygen of the tetrahedral reaction intermediate. Our studies also
      demonstrate that Asn(233) is not directly involved in the interaction with the
      substrates.

PMID- 11964170
TI  - Cell-specific activity of neprilysin 2 isoforms and enzymic specificity compared
      with neprilysin.
AB  - Neprilysin (NEP) 2 is a recently cloned glycoprotein displaying a high degree of
      sequence identity with neprilysin (EC 3.4.24.11), the prototypical member of the
      M13 subfamily of metalloproteases. Whereas NEP is involved in the metabolism of
      several bioactive peptides by plasma membranes of various cells, the enzymic
      properties and physiological functions of NEP2 are unknown. Here we characterize
      the cell-expression modalities and enzymic specificity of two alternatively
      spliced isoforms of NEP2 in Chinese hamster ovary and AtT20 cells. In the two
      cell lines, both isoforms are type II glycoproteins inserted in the endoplasmic
      reticulum as inactive precursors. Maturation detected by Western-blot analysis of
      glycosidase digests was cell-specific and more efficient in the endocrine cell
      line. The enzymic activity of both isoforms semi-purified from AtT20 cells
      reveals comparable specificities in terms of model substrates, pH optima and
      inhibitory patterns. NEP2 activity was compared with that of NEP regarding
      potencies of transition-state inhibitors, modes of hydrolysis, maximal hydrolysis
      rates and apparent affinities of bioactive peptides. Although all transition
      state inhibitors of NEP inhibited NEP2 activity, albeit with different potencies,
      and many peptides were cleaved at the same amide bond by both peptidases,
      differences could be observed, i.e. in the hydrolysis of gonadotropin-releasing
      hormone and cholecystokinin, which occurred at different sites and more
      efficiently in the case of NEP2. Differences in cleavage of bioactive peptides,
      in cell-trafficking patterns and in tissue distribution indicate that NEP and
      NEP2 play distinct physiological roles in spite of their high degree of sequence
      identity.

PMID- 11964171
TI  - Molecular and immunological characterization and IgE epitope mapping of Pen n 18,
      a major allergen of Penicillium notatum.
AB  - The mould genus, Penicillium, is a significant source of environmental aero
      allergens. A major allergen from Penicillium notatum, Pen n 18, was identified by
      two-dimensional immunoblotting using monoclonal antibody G11A10, raised against
      the vacuolar serine protease of Penicillium citrinum, followed by matrix-assisted
      laser-desorption ionization-time-of-flight MS analysis of the peptide digest. Pen
      n 18 was then cloned and the amino acid sequence deduced from the cDNA sequence.
      The cDNA encoded a 494 amino acid protein, considerably larger than mature Pen n
      18, the differences being due to the N- and C-terminal prosequences. The deduced
      amino acid sequence showed extensive similarity with those of vacuolar serine
      proteases from various fungi. The Pen n 18 coding sequence was expressed in
      Escherichia coli as a His-tagged fusion protein and purified by Ni(2+)-chelate
      affinity chromatography. On immunoblots, the purified recombinant protein
      specifically bound IgE from mould-allergic patients, and cross-inhibition assays
      demonstrated the presence of common IgE-binding epitopes on Pen n 18 and a major
      allergen of P. citrinum, Pen c 18. When mapping of the allergenic epitopes was
      performed, at least nine different linear IgE-binding epitopes, located
      throughout the Pen n 18 protein, were identified. Of these, peptide C12, located
      in the N-terminal region of the molecule, was recognized by serum from 75% of the
      patients tested and therefore appears to be an immunodominant IgE-binding
      epitope.

PMID- 11964172
TI  - Differential effect of the inhibition of Grb2-SH3 interactions in platelet
      activation induced by thrombin and by Fc receptor engagement.
AB  - The adaptor protein Grb2 (growth factor receptor-bound protein 2) is involved in
      cell proliferation via the Ras signalling pathway. In order to study the role of
      Grb2 in blood platelet responses, we used a peptide containing two proline-rich
      sequences derived from Sos (peptidimer), which binds to Grb2-Src homology 3
      domain (SH3) with a high affinity, and hence inhibits Grb2-SH3-mediated protein
      interactions. Platelet aggregation and 5-hydroxytryptamine (serotonin) release
      measured in the presence of the peptidimer were: (i) significantly decreased when
      induced by thrombin; and (ii) potentiated when induced by the engagement of the
      Fc receptor. In thrombin-activated platelets, the Grb2-SH2 domain formed an
      association with the beta3 subunit of the alphaIIb-beta3 integrin (GPIIb-IIIa),
      Shc, Syk, Src and SHP1 (SH2-containing phosphotyrosine phosphatase 1), whereas
      these associations did not occur after the engagement of the receptor for the Fc
      domain of IgG (FcgammaRIIa) or in resting platelets. Grb2-SH3 domains formed an
      association with the proline-rich sequences of Sos and Cbl in both resting and
      activated platelets, since the peptidimer abolished these associations.
      Inhibition of both fibrinogen binding and platelet aggregation by the peptide
      RGDS (Arg-Gly-Asp-Ser) had no effect on thrombin-induced Grb2-SH2 domain
      association with the aforementioned signalling molecules, indicating that these
      associations occurred during thrombin-induced 'inside-out' signalling. Platelet
      aggregation induced by direct activation via alphaIIb-beta3 ('outside-in'
      signalling) was potentiated by the peptidimer. The results show that inhibition
      of Grb2-SH3 interactions with signal-transduction proteins down-regulates
      thrombin-induced platelet activation, but also potentiates Fc receptor- and
      alphaIIb-beta3-mediated platelet activation.

PMID- 11964173
TI  - Characterization of a novel inhibitor of cytosolic phospholipase A2alpha,
      pyrrophenone.
AB  - Cytosolic phospholipase A(2)alpha (cPLA(2)alpha), one of the three subtypes of
      cPLA(2) (alpha, beta and gamma), is thought to be a rate-limiting enzyme in
      eicosanoid biosynthesis. We developed a novel and potent cPLA(2)alpha inhibitor
      with an optically active pyrrolidine, termed pyrrophenone, and characterized this
      compound in detail using enzyme and cellular assay systems. Pyrrophenone, which
      shows strong inhibition of cPLA(2)alpha activity, is one of the most potent
      cPLA(2)alpha inhibitors reported to date. Similar inhibitory potencies for
      cPLA(2)alpha were obtained from three different assays. The inhibitory activity
      of pyrrophenone is two or three orders of magnitude more potent than arachidonyl
      trifluoromethyl ketone (AACOCF(3)) under the same assay conditions. Pyrrophenone
      shows reversible inhibition of cPLA(2)alpha and displays no characteristics of
      the slow-binding inhibition observed for AACOCF(3). Pyrrophenone also inhibited
      the esterase and lysophospholipase activities of cPLA(2)alpha. However, the
      inhibition by pyrrophenone of 14 kDa secretory PLA(2)s, types IB and IIA, was
      over two orders of magnitude less potent than that for cPLA(2)alpha. Pyrrophenone
      strongly inhibited arachidonic acid release in calcium ionophore (A23187)
      stimulated human monocytic cells (THP-1 cells) in a dose-dependent manner with an
      IC(50) value of 0.024 microM, followed by suppression of eicosanoid synthesis,
      and also showed dose-dependent inhibition for interleukin-1-induced prostaglandin
      E(2) synthesis in human renal mesangial cells with an IC(50) value of 0.0081
      microM. The mechanism of inhibition of eicosanoid synthesis in these cell-based
      assays was due to inhibition of only one step of arachidonic acid release without
      any effect on cyclo-oxygenase or lipoxygenase pathways. These results suggest
      that pyrrophenone could be a potential therapeutic agent for inflammatory
      diseases.

PMID- 11964174
TI  - Utilization of green fluorescent protein as a marker for studying the expression
      and turnover of the monocarboxylate permease Jen1p of Saccharomyces cerevisiae.
AB  - Green fluorescent protein (GFP) from Aequorea victoria was used as an in vivo
      reporter protein when fused to the C-terminus of the Jen1 lactate permease of
      Saccharomyces cerevisiae. The Jen1 protein tagged with GFP is a functional
      lactate transporter with a cellular abundance of 1670 molecules/cell, and a
      catalytic-centre activity of 123 s(-1). It is expressed and tagged to the plasma
      membrane under induction conditions. The factors involved in proper localization
      and turnover of Jen1p were revealed by expression of the Jen1p-GFP fusion protein
      in a set of strains bearing mutations in specific steps of the secretory and
      endocytic pathways. The chimaeric protein Jen1p-GFP is targeted to the plasma
      membrane via a Sec6-dependent process; upon treatment with glucose, it is
      endocytosed via END3 and targeted for degradation in the vacuole. Experiments
      performed in a Deltadoa4 mutant strain showed that ubiquitination is associated
      with the turnover of the permease.

PMID- 11964175
TI  - Threonine-124 and phenylalanine-448 in Citrobacter freundii tyrosine phenol-lyase
      are necessary for activity with L-tyrosine.
AB  - Thr-124 and Phe-448 are located in the active site of Citrobacter freundii
      tyrosine phenol-lyase (TPL) near the phenol ring of a bound substrate analogue, 3
      (4'-hydroxyphenyl)propionic acid [Sundararaju, Antson, Phillips, Demidkina,
      Barbolina, Gollnick, Dodson and Wilson (1997) Biochemistry 36, 6502-6510]. Thr
      124 is replaced by Asp and Phe-448 is replaced by His in the crystal structure of
      a structurally similar enzyme, Proteus vulgaris tryptophan indole-lyase, which
      has 50% identical residues. Hence, Thr-124 and Phe-448 in TPL were mutated to Ala
      or Asp, and His, respectively, in order to probe the role of these residues in
      the reaction specificity for L-Tyr. These mutant enzymes have little or no beta
      elimination activity with L-Tyr or 3-fluoro-L-Tyr as a substrate, but retain
      significant elimination activity with S-(o-nitrophenyl)-L-cysteine, S-alkyl-L
      cysteines and beta-chloroalanine. Furthermore, the binding of L-Tyr and other non
      substrate amino acids is not significantly affected by the mutations. The mutant
      TPLs form intermediates in rapid-scanning stopped-flow experiments with L-Phe, L
      Tyr and L-Trp, similar to those seen with wild-type TPL. These results
      demonstrate that Thr-124 and Phe-448 are necessary for the reaction specificity
      of TPL for L-Tyr, and probably play a role in the elimination stage of the
      reaction mechanism. Thr-124 is within hydrogen-bonding distance of the phenolic
      group of the bound substrate, and may help to orientate the ring for beta
      elimination to occur. Phe-448 may be important to allow the formation of the
      closed conformation during the reaction.

PMID- 11964176
TI  - Oxidized lipid accumulates in the presence of alpha-tocopherol in
      atherosclerosis.
AB  - Oxidative modification of low-density lipoproteins in the arterial wall is a key
      feature of atherogenesis and widely believed to cause and/or accelerate lesion
      development. Linked to this is the expectation that vascular antioxidants are
      depleted during oxidation in vivo. However, whether alpha-tocopherol (vitamin E),
      an important lipid-soluble antioxidant, is depleted early in atherogenesis and
      can prevent lipid peroxidation in vivo is unresolved. To address this we examined
      the content of specific configurational isomers (cis/trans) of lipid
      hydro(pero)xides in lesions, which represent the major non-enzymic oxidation
      products, as formation and accumulation of cis/trans isomers is influenced by
      alpha-tocopherol in studies in vitro. Concordant with our previous findings that
      large amounts of oxidized lipid co-exist with relatively normal alpha-tocopherol
      levels in human lesions, we now show that cis/trans isomers predominate over
      other products in human carotid and aortic lesions and in lesion lipoproteins.
      Further, dietary vitamin E supplementation of rabbits after arterial injury
      significantly increases both the aortic levels of alpha-tocopherol and the
      overall content of cis/trans isomers. These data are fully consistent with alpha
      tocopherol acting as a hydrogen donor during lipid oxidation in vivo and suggest
      that alpha-tocopherol does not prevent lipoprotein lipid oxidation in the
      diseased vessel wall.

PMID- 11964177
TI  - Inhibition of cell growth through inactivation of eukaryotic translation
      initiation factor 5A (eIF5A) by deoxyspergualin.
AB  - The mechanism of inhibition of cell growth by deoxyspergualin was studied using
      mouse mammary carcinoma FM3A cells. Results of studies using deoxyspergualin
      analogues showed that both the guanidinoheptanate amide and glyoxyspermidine
      moieties of deoxyspergualin were necessary to cause inhibition of cell growth.
      When deoxyspergualin was added to the medium, there was a strong inhibition of
      cell growth and formation of active eukaryotic translation initiation factor 5A
      (eIF5A) at the third day of culture. There was also a marked decrease in cellular
      putrescine content and a small decrease in spermidine content. Accumulation of
      decapped mRNA, which is typically associated with eIF5A deficiency in yeast, was
      also observed. The inhibition of cell growth and the formation of active eIF5A
      was not reversed by addition of spermidine. The activity of deoxyhypusine
      synthase, the first enzyme in the formation of active eIF5A, was inhibited by
      deoxyspergualin in a cell-free system. These results, taken together, indicate
      that inhibition of active eIF5A formation is strongly involved in the inhibition
      of cell growth by deoxyspergualin.

PMID- 11964178
TI  - Inhibition effects of furfural on alcohol dehydrogenase, aldehyde dehydrogenase
      and pyruvate dehydrogenase.
AB  - The kinetics of furfural inhibition of the enzymes alcohol dehydrogenase (ADH; EC
      1.1.1.1), aldehyde dehydrogenase (AlDH; EC 1.2.1.5) and the pyruvate
      dehydrogenase (PDH) complex were studied in vitro. At a concentration of less
      than 2 mM furfural was found to decrease the activity of both PDH and AlDH by
      more than 90%, whereas the ADH activity decreased by less than 20% at the same
      concentration. Furfural inhibition of ADH and AlDH activities could be described
      well by a competitive inhibition model, whereas the inhibition of PDH was best
      described as non-competitive. The estimated K(m) value of AlDH for furfural was
      found to be about 5 microM, which was lower than that for acetaldehyde (10
      microM). For ADH, however, the estimated K(m) value for furfural (1.2 mM) was
      higher than that for acetaldehyde (0.4 mM). The inhibition of the three enzymes
      by 5-hydroxymethylfurfural (HMF) was also measured. The inhibition caused by HMF
      of ADH was very similar to that caused by furfural. However, HMF did not inhibit
      either AlDH or PDH as severely as furfural. The inhibition effects on the three
      enzymes could well explain previously reported in vivo effects caused by furfural
      and HMF on the overall metabolism of Saccharomyces cerevisiae, suggesting a
      critical role of these enzymes in the observed inhibition.

PMID- 11964179
TI  - Expression and characterization of the active molecular forms of
      choline/ethanolamine kinase-alpha and -beta in mouse tissues, including carbon
      tetrachloride-induced liver.
AB  - Choline/ethanolamine kinase (ChoK/EtnK) exists as at least three isoforms
      (alpha1, alpha2 and beta) in mammalian cells. The physiological significance for
      the existence of more than one form of the enzyme, however, remains to be
      determined. In the present study, we examined the expression and distribution of
      the isoforms in mouse tissues using isoform-specific cDNA probes and polyclonal
      antibodies raised against each N-terminal peptide sequence. Both Northern- and
      Western-blot analyses indicated that either the alpha (alpha1 plus alpha2) or the
      beta isoform appeared to be the ubiquitously expressed enzyme. The mRNA abundance
      for the alpha isoform was highest in testis, whereas that for the beta isoform
      was relatively high in heart and liver. While the native form of each isoform was
      reported to consist of either homodimers or homotetramers, our immunotitration
      studies clearly indicated that a considerable part of the active form of the
      enzyme consists of alpha/beta hetero-oligomers, with relatively small parts of
      activity expressed by alpha/alpha and beta/beta homo-oligomers. This is the first
      experimental evidence for the presence of heteromeric ChoK/EtnK in any source.
      Thus our results strongly suggested that the activity of ChoK/EtnK in the cell is
      controlled not only by the level of each isoform but also by their combination to
      form the active oligomer complex. Carbon tetrachloride (CCl(4)) was shown to
      induce ChoK activity 2-4-fold in murine liver. Our analysis for the mechanism
      involved in this induction revealed that the responsible isoform for CCl(4) was
      alpha, not beta. The level of alpha mRNA was strongly induced in mouse liver,
      which resulted in a sustained increase in the amount of the alpha isoform.
      Consequently, the composition of alpha/alpha homo-oligomers came to represent up
      to 80% of the total active molecular form of ChoK in CCl(4)-induced liver,
      whereas it was less than 20% in normal uninduced liver.

PMID- 11964180
TI  - Mutation of conserved active-site threonine residues in creatine kinase affects
      autophosphorylation and enzyme kinetics.
AB  - Muscle-type creatine kinase (MM-CK) is a member of an isoenzyme family with key
      functions in cellular energetics. It has become a matter of debate whether the
      enzyme is autophosphorylated, as reported earlier [Hemmer, Furter-Graves, Frank,
      Wallimann and Furter (1995) Biochim. Biophys. Acta 1251, 81-90], or exclusively
      nucleotidylated. In the present paper, we demonstrate unambiguously that CK is
      indeed autophosphorylated. However, this autophosphorylation is not solely
      responsible for the observed microheterogeneity of MM-CK on two-dimensional
      isoelectric focusing gels. Using phosphoamino-acid analysis of (32)P-labelled CK
      isoforms, phosphothreonine (P-Thr) residues were identified as the only product
      of autophosphorylation for all CK isoenzymes. The phosphorylated residues in
      chicken MM-CK were allocated to a region in the vicinity of the active site,
      where five putative phosphorylation sites were identified. Site-directed
      threonine-valine-replacement mutants reveal that autophosphorylation is not
      specific for one particular residue but occurs at all examined threonine
      residues. The enzyme kinetic parameters indicate that the autophosphorylation of
      CK exerts a modulatory effect on substrate binding and the equilibrium constant,
      rather than on the catalytic mechanism itself.

PMID- 11964181
TI  - Association of the 72/74-kDa proteins, members of the heterogeneous nuclear
      ribonucleoprotein M group, with the pre-mRNA at early stages of spliceosome
      assembly.
AB  - We have investigated the role played in precursor mRNA (pre-mRNA) splicing by the
      protein pair of molecular size 72/74 kDa, which are integral components of a
      discrete subset of heterogeneous nuclear (hn) ribonucleoproteins (RNPs) named
      large heterogeneous nuclear RNP (LH-nRNP). This 72/74 kDa pair of proteins has
      been shown to belong to the hnRNP M group, and are referred to as 72/74(M). By
      applying specific immunoprecipitation assays in a consecutive series of splicing
      reactions in vitro, the antigenic 72/74(M) protein species were found to
      associate with the pre-mRNA and not the intermediate or final products of
      splicing. Kinetic studies, combined with isolation of pre-spliceosomal and
      spliceosomal complexes from the splicing reaction, indicated a loose association
      of 72/74(M) with both the initially formed H assembly and the first splicing
      committed E complex. Stable binding was seen at a later stage of the reaction,
      well in advance of the appearance of the first intermediate products of RNA
      splicing. Evidence is provided that supports the almost exclusive association of
      72/74(M) with pre-mRNA within the pre-spliceosomal A complex. This dynamic
      binding appeared to involve pre-mRNA sites similar to those of spliceosomal U1
      and U2 small nuclear RNP complexes. Moreover, a preferential binding to a
      truncated RNA containing the 5' exon-intron part, rather than the intron-3' exon
      part, of pre-mRNA was observed.

PMID- 11964182
TI  - The role of alpha-methylacyl-CoA racemase in bile acid synthesis.
AB  - According to current views, the second peroxisomal beta-oxidation pathway is
      responsible for the degradation of the side chain of bile acid intermediates.
      Peroxisomal multifunctional enzyme type 2 [peroxisomal multifunctional 2-enoyl
      CoA hydratase/(R)-3-hydroxyacyl-CoA dehydrogenase; MFE-2] catalyses the second
      (hydration) and third (dehydrogenation) reactions of the pathway. Deficiency of
      MFE-2 leads to accumulation of very-long-chain fatty acids, 2-methyl-branched
      fatty acids and C(27) bile acid intermediates in plasma, but bile acid synthesis
      is not blocked completely. In this study we describe an alternative pathway,
      which allows MFE-2 deficiency to be overcome. The alternative pathway consists of
      alpha-methylacyl-CoA racemase and peroxisomal multifunctional enzyme type 1
      [peroxisomal multifunctional 2-enoyl-CoA hydratase/(S)-3-hydroxyacyl-CoA
      dehydrogenase; MFE-1]. (24E)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholest-24
      enoyl-CoA, the presumed physiological isomer, is hydrated by MFE-1 with the
      formation of (24S,25S)-3alpha,7alpha,12alpha,24-tetrahydroxy-5beta-cholestanoyl
      CoA [(24S,25S)-24-OH-THCA-CoA], which after conversion by a alpha-methylacyl-CoA
      racemase into the (24S,25R) isomer can again be dehydrogenated by MFE-1 to 24
      keto-3alpha,7alpha,12alpha-trihydroxycholestanoyl-CoA, a physiological
      intermediate in cholic acid synthesis. The discovery of the alternative pathway
      of cholesterol side-chain oxidation will improve diagnosis of peroxisomal
      deficiencies by identification of serum 24-OH-THCA-CoA diastereomer profiles.

PMID- 11964183
TI  - Stopped-flow kinetic analysis of long-chain fatty acid dissociation from bovine
      serum albumin.
AB  - The kinetics of the interaction of long-chain fatty acids (referred to as fatty
      acids) with albumin is critical to understanding the role of albumin in fatty
      acid transport. In this study we have determined the kinetics of fatty acid
      dissociation from BSA and the BSA-related fatty acid probe BSA-HCA (BSA labelled
      with 7-hydroxycoumarin-4-acetic acid) by stopped-flow methods. Fatty acid-albumin
      complexes of a range of natural fatty acid types and albumin molecules (donors)
      were mixed with three fatty acid-binding acceptor proteins. Dissociation of fatty
      acids from the donor was monitored by either the time course of donor
      fluorescence/absorbance or the time course of acceptor fluorescence. The results
      of these measurements indicate that fatty acid dissociation from BSA as well as
      BSA-HCA is well described by a single exponential function over the entire range
      of fatty acid/albumin molar ratios used in these measurements, from 0.5:1 to 6:1.
      The observed rate constants (k(obs)) for the dissociation of each fatty acid type
      reveal little or no dependence on the initial fatty acid/albumin ratio. However,
      dissociation rates were dependent upon the type of fatty acid. In the case of
      native BSA with an initial fatty acid/BSA molar ratio of 3:1, the order of k(obs)
      values was stearic acid (1.5 s(-1)) < oleic acid < palmitic acid congruent with
      linoleic acid<arachidonic acid (8 s(-1)) at 37 degrees C. The corresponding
      values for BSA-HCA were about half the values for BSA. The results of this study
      show that the rate of fatty acid dissociation from native BSA is more than 10
      fold faster than reported previously and that the off-rate constants for the five
      primary fatty acid-binding sites differ by less than a factor of 2. We conclude
      that for reported rates of fatty acid transport across cell membranes,
      dissociation of fatty acids from the fatty acid-BSA complexes used in the
      transport studies should not be rate-limiting.

PMID- 11964184
TI  - Mo(V) co-ordination in the periplasmic nitrate reductase from Paracoccus
      pantotrophus probed by electron nuclear double resonance (ENDOR) spectroscopy.
AB  - The first electron nuclear double resonance (ENDOR) study of a member of the Mo
      bis-molybdopterin guanine dinucleotide family of molybdoenzymes is presented,
      using the periplasmic nitrate reductase from Paracoccus pantotrophus. Rapid
      freeze-quenched time-resolved EPR revealed that during turnover the intensity of
      a Mo(V) EPR signal known as High-g [resting] increases. This signal is split by
      two interacting protons that are not solvent-exchangeable. X-band proton-ENDOR
      analysis resolved broad symmetrical resonance features that arose from four
      classes of protons weakly coupled to the Mo(V). Signals from two of these were
      lost upon exchange into deuterated buffer, suggesting that they may originate
      from OH(-) or H(2)O groups. One of these signals was also lost when the enzyme
      was redox-cycled in the presence of azide. Since these protons are very weakly
      coupled OH/H(2)O groups, they are not likely to be ligated directly to the Mo(V).
      This suggests that protonation of a Mo(VI)zO group does not occur on reduction to
      Mo(V), but most probably accompanies reduction of Mo(V) to Mo(IV). A resonance
      feature from a more strongly coupled proton, that was not lost following exchange
      into deuterated buffer, could also be resolved at 22-24 MHz. The anisotropy of
      this feature, determined from ENDOR spectra collected at a range of field
      positions, indicated a Mo-proton distance of approx. 3.2 A, consistent with this
      being one of the beta-methylene protons of a Mo-Cys ligand.

PMID- 11964185
TI  - Characterization of Streptococcus pneumoniae thymidylate kinase: steady-state
      kinetics of the forward reaction and isothermal titration calorimetry.
AB  - Thymidylate kinase (TMK) catalyses the phosphorylation of dTMP to form dTDP in
      both the de novo and salvage pathways of dTTP synthesis. The tmk gene from the
      bacterial pathogen Streptococcus pneumoniae was identified. The gene, encoding a
      212-amino-acid polypeptide (23352 Da), was cloned and overexpressed in
      Escherichia coli with an N-terminal hexahistidine tag. The enzyme was purified to
      homogeneity, and characterized in the forward reaction. The pH profile of TMK
      indicates that its activity is optimal at pH 8.5. The substrate specificity of
      the enzyme was examined; it was found that not only ATP, but also dATP and to a
      lesser extent CTP, could act as phosphate donors, and dTMP and dUMP could serve
      as phosphate acceptors. Furthermore, AZT-MP (3'-azido-3'-deoxythymidine 5'
      monophosphate) was shown not to be a substrate for S. pneumoniae TMK. Steady
      state kinetics and inhibition studies with adenosine 5'-[beta-thio]diphosphate
      and dTDP in addition to isothermal titration calorimetry were performed. The data
      showed that binding follows an ordered pathway, in which ATP binds first with a
      K(m) of 235 +/- 46 microM and a K(d) of 116 +/- 3 microM, and dTMP binds secondly
      with a K(m) of 66 +/- 12 microM and a K(d) of 53 +/- 2 microM.

PMID- 11964186
TI  - Glutathione synthetase from Plasmodium falciparum.
AB  - GSH is the major low-molecular-mass thiol in most organisms. The tripeptide
      maintains a reduced intracellular environment and protects cellular components
      from damaging oxidation. GSH is synthesized by the action of two ATP-dependent
      enzymic steps, in which gamma-glutamylcysteine synthetase (gamma-GCS) catalyses
      the ligation of glutamate and cysteine and subsequently glutathione synthetase
      (GS) adds glycine to the dipeptide. Recently it was shown that the synthesis of
      gamma-glutamylcysteine is crucial for the survival of the erythrocytic stages of
      the malaria parasite Plasmodium falciparum by using the specific gamma-GCS
      inhibitor buthionine sulphoximine. In order to investigate further the synthetic
      pathway of the tripeptide in the parasite, GS was cloned and expressed
      recombinantly. The deduced amino acid sequence of P. falciparum GS shares only a
      moderate degree of identity with other known GSs, but the residues responsible
      for substrate and co-factor binding are almost all conserved, with the exception
      of the ones involved in gamma-glutamylcysteine binding. The protein is active as
      a dimer, with a subunit molecular mass of 77 kDa, and the addition of reducing
      reagents such as dithiothreitol is essential in maintaining enzymic activity,
      indicating that thiol groups are important for stability and enzymic activity.
      The K(app)(m) values for gamma-glutamyl-alpha-aminobutyrate, ATP and glycine were
      determined to be 107.1 microM, 59.1 microM and 5.04 mM, respectively, and the
      V(max) of 5.24 +/- 0.7 micromol.min(-1).mg(-1) was in the same range as that of
      the mammalian enzymes. However, the negative co-operativity observed for gamma
      glutamylcysteine binding to the rat enzyme was not found for the parasite
      protein. This may be due to the alteration of several amino acids in the gamma
      glutamylcysteine-binding site.

PMID- 11964189
TI  - Use of the direct puncture technique in management of capillaro-venous
      malformations: case report.
AB  - BACKGROUND: Preoperative devascularization of the capillaro-venous malformations
      located in the aero-digestive tract is important for surgeons, to minimize blood
      loss during surgical excision of malformations. CASE PRESENTATION: Here we
      present two cases of capillaro-venous malformation in which we could successfully
      achieve preoperative devascularization, by directly injecting n-butyl cyano
      acrylate into the capillaro-venous bed. This technique is relatively easy, safe
      and cheap, and can be carried out immediately before surgery.

PMID- 11964188
TI  - Effective generation of transgenic pigs and mice by linker based sperm-mediated
      gene transfer.
AB  - BACKGROUND: Transgenic animals have become valuable tools for both research and
      applied purposes. The current method of gene transfer, microinjection, which is
      widely used in transgenic mouse production, has only had limited success in
      producing transgenic animals of larger or higher species. Here, we report a
      linker based sperm-mediated gene transfer method (LB-SMGT) that greatly improves
      the production efficiency of large transgenic animals. RESULTS: The linker
      protein, a monoclonal antibody (mAb C), is reactive to a surface antigen on sperm
      of all tested species including pig, mouse, chicken, cow, goat, sheep, and human.
      mAb C is a basic protein that binds to DNA through ionic interaction allowing
      exogenous DNA to be linked specifically to sperm. After fertilization of the egg,
      the DNA is shown to be successfully integrated into the genome of viable pig and
      mouse offspring with germ-line transfer to the F1 generation at a highly
      efficient rate: 37.5% of pigs and 33% of mice. The integration is demonstrated
      again by FISH analysis and F2 transmission in pigs. Furthermore, expression of
      the transgene is demonstrated in 61% (35/57) of transgenic pigs (F0 generation).
      CONCLUSIONS: Our data suggests that LB-SMGT could be used to generate transgenic
      animals efficiently in many different species.

PMID- 11964190
TI  - International variation in ethics committee requirements: comparisons across five
      Westernised nations.
AB  - BACKGROUND: Ethics committees typically apply the common principles of autonomy,
      nonmaleficence, beneficence and justice to research proposals but with variable
      weighting and interpretation. This paper reports a comparison of ethical
      requirements in an international cross-cultural study and discusses their
      implications. DISCUSSION: The study was run concurrently in New Zealand, UK,
      Israel, Canada and USA and involved testing hypotheses about believability of
      testimonies regarding alleged child sexual abuse. Ethics committee requirements
      to conduct this study ranged from nil in Israel to considerable amendments
      designed to minimise participant harm in New Zealand. Assessment of minimal risk
      is a complex and unreliable estimation further compounded by insufficient
      information on probabilities of particular individuals suffering harm. Estimating
      potential benefits/ risks ratio and protecting participants' autonomy similarly
      are not straightforward exercises. SUMMARY: Safeguarding moral/humane principles
      should be balanced with promotion of ethical research which does not impede
      research posing minimal risk to participants. In ensuring that ethical standards
      are met and research has scientific merit, ethics committees have obligations to
      participants (to meet their rights and protect them from harm); to society (to
      ensure good quality research is conducted); and to researchers (to treat their
      proposals with just consideration and respect). To facilitate meeting all these
      obligations, the preferable focus should be promotion of ethical research, rather
      than the prevention of unethical research, which inevitably results in the
      impediment of researchers from doing their work. How the ethical principles
      should be applied and balanced requires further consideration.

PMID- 11964191
TI  - Selective searching while driving: the role of experience in hazard detection and
      general surveillance.
AB  - Novice drivers have been found in previous studies to display a limited search of
      the immediate environment, relative to experienced drivers, when manoeuvring on a
      dual-carriageway road. The present study investigated whether this reduction in
      the variance of search along the horizontal plane was a product of less frequent
      glancing in the car's mirrors. Novice and experienced drivers were observed as
      they made lane changes in relatively unobstructed conditions and when they needed
      to move into a lane already occupied by traffic. Novice drivers were found to
      rely more than experienced drivers upon their internal mirror, even when the lane
      changing manoeuvre required information about traffic in the lane best reflected
      in the external, door-mounted mirror. Novices did increase their use of the
      external mirror in response to driving needs, suggesting that they did have an
      awareness of the situation that required inter-weaving with traffic in their
      destination lane. Their reliance upon the internal mirror may be a product of a
      habit acquired specifically for the driver licensing examination, in which
      exaggerated inspection of the internal mirror is regarded as being desirable.

PMID- 11964192
TI  - The activation of mechanisms linking judgements of work design and management
      with musculoskeletal pain.
AB  - The report of work-related musculoskeletal pain may be related to worker
      evaluations of the design and management of work through two mechanisms: one
      biomechanical and the other stress-related. This study of engineering workers (n
      = 204) explored the validity of these mechanisms using sequential logistic
      regression. Analyses suggested that workers' ratings of the adequacy of the
      design and management of their work were related to their report of work-related
      musculoskeletal pain. However, the mechanisms appeared to be activated in certain
      conditions. The reporting of pain in the upper body was both biomechanically- and
      stress-related, whereas that in the lower body was only biomechanically-related.
      It is argued that the mechanism activated appeared to be determined by the
      anatomical location of the pain, and probably the variance shared between the
      different aspects of work design and management, on the one hand, and the
      mechanical load of the job, on the other.

PMID- 11964193
TI  - The influence of climatic factors on non-specific back and neck-shoulder disease.
AB  - An epidemiological study was carried out to explore the relationship between
      climatic factors and non-specific low-back and neck-shoulder symptoms in working
      populations. In a review of published literature, 27 studies were found which
      related climatic factors to musculoskeletal symptoms, but none of these studies
      specifically addressed the subject. It can be concluded that a relationship
      between climatic factors and musculoskeletal symptoms is considered at least
      plausible by both researchers, workers and patients, but that the epidemiological
      evidence appearing from literature is very weak. Questionnaire data which were
      collected on musculoskeletal symptoms, workload and perceptions of climatic
      conditions of 2030 workers in 24 different occupations were analysed multi
      variately. About one-quarter of the workers related symptoms of the low back and
      neck-shoulders to climatic factors. They perceived climatic factors in most cases
      as aggravating factors for their symptoms. No seasonal influence on prevalence
      rates was reported. For low-back and neck-shoulder symptoms and for sick leave
      due to neck-shoulder symptoms, an association was found with climatic factors,
      and in particular with respect to draughts in relation to neck-shoulder symptoms.
      In addition, neck-shoulder symptoms were negatively related to frequent outdoor
      work. The findings suggest a relationship between climatic factors and
      musculoskeletal symptoms and call for further detailed investigations.

PMID- 11964194
TI  - Quantitative prediction of body diameter in severely obese individuals.
AB  - The prevalence of obesity and severe obesity continues to increase in the
      developed world. Apart from obesity's strong association with a variety of health
      conditions, severely obese individuals (i.e. > or = 300 lb [136 kg]) sometimes
      have difficulty with ambulation, and often cannot use regular sized clothes,
      furniture, and assistive devices such as walkers and wheelchairs. The purpose of
      this study was to assess the relationship between linear body measurements
      (anthropometry) and weight in severely obese people in order to generate
      equations to predict such measurements from weight alone. Various body size
      measurements were obtained from three independent data sets (74 severely obese
      individuals evaluated at the New York Obesity Research Center, 103 severely obese
      individuals who participated in the National Center for Health Statistics'
      National Health and Nutrition Examination Survey III, and a further 90 severely
      obese individuals evaluated at the New York Obesity Research Center). Linear
      regression analyses revealed that for each increase of 10 kg (22.04 lb) above 136
      kg (300 lb), body diameter measurements increase by 0.9-1.1 cm. These analyses
      provide body size-to-weight estimates that may help manufacturers develop
      products and services that are more appropriate for increasing numbers of
      severely obese individuals.

PMID- 11964196
TI  - Ergonomics International.

PMID- 11964195
TI  - Impact of speech presentation level on cognitive task performance: implications
      for auditory display design.
AB  - Speech displays and verbal response technologies are increasingly being used in
      complex, high workload environments that require the simultaneous performance of
      visual and manual tasks. Examples of such environments include the flight decks
      of modern aircraft, advanced transport telematics systems providing invehicle
      route guidance and navigational information and mobile communication equipment in
      emergency and public safety vehicles. Previous research has established an
      optimum range for speech intelligibility. However, the potential for variations
      in presentation levels within this range to affect attentional resources and
      cognitive processing of speech material has not been examined previously. Results
      of the current experimental investigation demonstrate that as presentation level
      increases within this 'optimum' range, participants in high workload situations
      make fewer sentence-processing errors and generally respond faster. Processing
      errors were more sensitive to changes in presentation level than were measures of
      reaction time. Implications of these findings are discussed in terms of their
      application for the design of speech communications displays in complex multi
      task environments.

PMID- 11964197
TI  - The effect of vehicle characteristics on drivers' risk-taking behaviour.
AB  - There is evidence linking certain vehicle characteristics to crash involvement
      and one possible mechanism behind this relationship is that these vehicle
      characteristics influence drivers' risk-taking behaviour. In order to investigate
      this, we conducted a roadside observation survey and a questionnaire-based study.
      Both revealed a significant relationship between vehicle performance and drivers'
      risk-taking behaviour. The causal direction of this relationship has important
      consequences. If drivers' risk taking predicts their car choice, then it could be
      justifiably argued that individuals who take more risks when driving simply
      choose more powerful vehicles to facilitate their behaviour. However, if it is
      the case that vehicle characteristics adversely influence drivers' risk-taking
      propensity then this has implications for vehicle design. Results indicated that
      the causal pathway operates independently in both directions. Finally, we sought
      to determine which vehicle characteristics influenced risk-taking intentions
      independently of other confounded characteristics. We found that high vehicle
      performance and a greater number of safety features led independently to greater
      intended risk taking in general, while higher internal car noise led to closer
      car following and more risky gap acceptance, but not to greater speed. Vehicle
      smoothness and handling did not affect risk-taking intentions.

PMID- 11964198
TI  - Combined and interacting effects of hand and head movement delays on discrete
      manual performance in a virtual environment.
AB  - Transmission delays occur when a virtual environment responds to the hand and
      head movements of an operator. The effects of hand and head-related delays on
      discrete manual performance was investigated experimentally and compared. Imposed
      hand and head-related pure delays equal to or greater than 110 ms and 220 ms,
      respectively, significantly increased hand Movement Time (MT). The effect of hand
      related delays was greater than that of head-related delays of the same
      magnitude. A regression model describing the combined effects of both delays on
      MT is reported (R(2) = 0.95). Analyses of the interactions among delays, target
      width, and distances have shown the need to adopt the traditional classification
      of delays into (1) control delay, and (2) display delay. The use of this taxonomy
      and the regression analyses to describe and explain the effects of individual and
      combined effects of delays on discrete target-reaching task performance in
      virtual environments are discussed.

PMID- 11964199
TI  - Evaluation of draught in the workplace.
AB  - During 826, 1-h sessions 107 participants (33 women, 74 men, 18-51 years of age)
      were exposed to defined draughts where air velocity (0.1 < or = V(a) < or = 0.4 m
      s(-1)), turbulence intensity (< 30, approximately equal to 50, > 70%), draught
      direction (horizontal, vertical, diagonal), air temperature (11 < or = t(a) < or
      = 23 degrees C), and metabolic rate ( approximately equal to 60< or = M < or =
      156 W m(-2)) were varied but kept constant during single sessions. Perception and
      evaluation (annoyance due to draught and local cold) were registered using a list
      of prescribed body parts. Annoyance due to draught increased with the increase in
      mean air velocity and in turbulence intensity, as well as with the decrease in
      air temperature and in metabolic rate. The direction of air flow had no
      influence. As these responses were neither sufficiently predicted by the draught
      rating model proposed in ISO 7730 (1994), nor by its extension developed by
      Toftum (1994a), the latter was modified according to the data registered in this
      paper. Using the modified model the accordingly predicted percentage of people
      annoyed by draught agreed highly with the percentage actually observed (r=0.726,
      p<0.001). As the resulting model covers larger ranges of air temperature and
      metabolic rate it is suggested that it should substitute the model proposed in
      ISO 7730 [1994].

PMID- 11964200
TI  - Anthropometric differences among occupational groups.
AB  - The increasing demands for anthropometric information for the design of machinery
      and personal protective equipment to prevent occupational injuries has
      necessitated an understanding of the anthropometric differences to be found among
      occupations. This study identified differences in various body measurements
      between occupational groups in the USA, as determined in the third National
      Health and Nutrition Examination Survey. Approximately 16,000 of its 32,900
      subjects were associated with an occupational group. The analysis of the data
      showed that the body size, or body segment measurements, of some occupational
      groups differ significantly. For example, agricultural workers were shorter by an
      average of 2.5 cm in height, and had wider wrist breadths, than other workers.
      Female agricultural and manufacturing workers had larger waist circumferences
      than those in the 'other occupations' and 'all occupations' categories.
      Protective service workers (i.e. firefighters, police and guards) were taller and
      heavier (7 kg heavier for males and over 10 kg heavier for females) than those in
      all occupations combined. These differences and other deviations as well as some
      age-and-ethnicity-adjusted results were tabulated for users' reference.
      Researchers and designers who use anthropometric databases to evaluate human
      machine interfaces and personal protective equipment (PPE) must use caution in
      selecting databases that are adequate for their occupational applications.

PMID- 11964201
TI  - Evaluation of a prototype multi-posture office chair.
AB  - Office chairs have often been designed to promote a single 'correct' rather rigid
      and upright posture, yet it is acknowledged that allowing changes in posture is
      good ergonomics practice. The present study investigated office worker's
      preferences for a standard shaped typist's chair (ST) and a prototype multi
      posture (PMP) office chair designed to allow its users a variety of sitting
      positions. Forty-two (22 male and 20 female) telesales personnel (12), clerical
      staff (12) and researchers (18) used ST or PMP in their workplace for the first
      week of a 2-week study (with an even number in each work area). The PMP chair was
      introduced to participants with a brief lecture on how to use it and with an
      information booklet. Following this, each participant completed a chair comfort
      questionnaire. In the second week, participants swapped chairs and again
      completed the chair comfort questionnaire. At the end of the second week
      participants were also asked to complete a separate questionnaire about the
      usability of the information booklet that accompanied the PMP chair.
      Statistically significant differences in subject's rating of the two chairs were
      observed in 7 out of 19 questions. On a 100 mm scale, the ST chair was rated as
      having a greater mean overall acceptability, desirability and suitability for
      body build than the PMP chair. Participants also claimed to achieve better
      posture in the ST chair, that they tipped forward less and were more satisfied
      with its width. Although the participants generally preferred the ST chair, the
      PMP chair received more favourable ratings among the researchers who were quite
      mobile in their work, and in whom there was a trend for less neck, shoulder and
      upper back discomfort. More participants reported an overall preference for the
      PMP chair. The findings suggest that a more aesthetically acceptable PMP chair
      should be developed, peoples' reasons for preferring a more traditionally
      designed chair should be explored, and that the effect of postural stability
      education on personal preconceptions should be examined to obtain an optimal
      combination of healthy sitting habits, comfort and aesthetic qualities in an
      office chair.

PMID- 11964202
TI  - An analysis of 'looked but failed to see' accidents involving parked police
      vehicles.
AB  - Drivers who collide with a vehicle that is parked on the hard shoulder of a
      motorway or dual-carriageway sometimes claim not to have seen it before the
      collision. Previous research into vehicle conspicuity has taken such 'looked but
      failed to see' claims at face value, and concentrated on attempting to remedy the
      problem by making vehicles more conspicuous in sensory terms. However, the
      present study describes investigations into accidents of this kind which have
      involved stationary police cars, vehicles which are objectively highly
      conspicuous. Two laboratory studies showed that experienced drivers viewing a
      film of dual-carriageway driving were slower to respond to a parked police car as
      a 'hazard' if it was parked directly in the direction of travel than if it was
      parked at an angle; this effect was more pronounced when the driver's attention
      was distracted with a secondary reasoning task. Taken together with the accident
      reports, these results suggest that 'looked but failed to see' accidents may
      arise not because the parked vehicle is difficult to see, but for more cognitive
      reasons, such as vigilance failure, or possession by the driver of a 'false
      hypothesis' about the road conditions ahead. An emergency vehicle parked in the
      direction of travel, with only its blue lights flashing, may encourage drivers to
      believe that the vehicle is moving rather than stationary. Parking at an angle in
      the road, and avoiding the use of blue lights alone while parked, are two steps
      that drivers of parked emergency vehicles should consider taking in order to
      alert approaching drivers to the fact that a stationary vehicle is ahead.

PMID- 11964204
TI  - Music is as distracting as noise: the differential distraction of background
      music and noise on the cognitive test performance of introverts and extraverts.
AB  - Previous research has found that introverts' performance on complex cognitive
      tasks is more negatively affected by distracters, e.g. music and background
      television, than extraverts' performance. This study extended previous research
      by examining whether background noise would be as distracting as music. In the
      presence of silence, background garage music and office noise, 38 introverts and
      38 extraverts carried out a reading comprehension task, a prose recall task and a
      mental arithmetic task. It was predicted that there would be an interaction
      between personality and background sound on all three tasks: introverts would do
      less well on all of the tasks than extraverts in the presence of music and noise
      but in silence performance would be the same. A significant interaction was found
      on the reading comprehension task only, although a trend for this effect was
      clearly present on the other two tasks. It was also predicted that there would be
      a main effect for background sound: performance would be worse in the presence of
      music and noise than silence. Results confirmed this prediction. These findings
      support the Eysenckian hypothesis of the difference in optimum cortical arousal
      in introverts and extraverts.

PMID- 11964203
TI  - Maximal oxygen uptake during cycling is reduced in moving environments;
      consequences for motion-induced fatigue.
AB  - In previous studies on physical fatigue during simulated ship movements, the
      apparent exhaustion of subjects after experimentation suggested that the
      traditional index of physical workload, oxygen consumption expressed as the
      percentage of peak oxygen consumption (VO2-peak) measured in a separate graded
      exercise test (GXT), underestimates workload in a moving environment. In these
      studies, the GXT was carried out in a stationary environment, as is standard
      practice. To explain the underestimation, it was hypothesized that VO2-peak might
      have been less if the GXT had been carried out in the moving environment. This
      paper reports on three experimental tests of this hypothesis, performed with a
      ship motion simulator and aboard a ship at sea. In all three experiments, VO2
      peak was indeed significantly reduced when the GXT was carried out in the moving
      environment. Theoretical reasons for this phenomenon are discussed and
      investigated, but a clear explanation is still lacking.

PMID- 11964205
TI  - An investigation of heat stress effects on time-sharing performance.
AB  - A study was conducted to investigate the effects of heat stress on time-sharing
      performance. Twelve participants performed three dual-task scenarios and a
      multiple-task scenario for 2 h in each of six climates. The climates were
      obtained by generating each of three wet bulb globe temperatures (WBGT; 22, 28
      and 34 degrees C) with two relative humidity levels (30 and 70%). The dual tasks
      selected from the Criterion Task Set (CTS) were: (1) display monitoring with
      mathematical processing; (2) memory search with mathematical processing; and (3)
      unstable tracking with memory search. The multiple task scenario was generated
      using the SYNTASK software. The results indicated a significant heat stress
      effect on CTS display monitoring and unstable tracking performance and on the
      SYNTASK visual monitoring and auditory discrimination tasks. Additionally, at 34
      degrees C WBGT, 70% relative humidity was more detrimental to performance than
      30% relative humidity. Results were interpreted using the Maximal Adaptability
      Model and Shingledecker's information processing stage/resource framework. To
      describe the results in an orderly manner, the authors propose the concept of
      heat stress selectivity effects. In addition, the results were used to evaluate
      whether the most recent NIOSH recommended heat stress standard, which is based
      solely on physiological and medical criteria, protects time-sharing performance.
      It was concluded that the NIOSH criterion does offer protection up to 28 degrees
      C WBGT.

PMID- 11964206
TI  - Reliability of the vertical spinal creep response measured in sitting
      (asymptomatic and low-back pain subjects).
AB  - Vertical spinal creep (or change in stature) has been used as an index of spinal
      loading, yet reliability of the testing protocol has not been fully examined.
      This study investigated the reliability of a vertical spinal creep response in 10
      asymptomatic and five low-back pain subjects. Each subject performed the 25-min
      testing protocol, which consisted of three phases (5-min preload, 10-min loaded
      and 10-min unloaded), at the same time on two separate days. Good reliabilities
      in vertical spinal creep response between two days of testing were demonstrated
      for both asymptomatic and low-back pain subjects.

PMID- 11964207
TI  - Should we routinely test for simultaneous location and scale changes?
AB  - It is argued that in many circumstances, there is no compelling reason to believe
      that measurements from several experimental groups have the same variability. If
      it is plausible that the variabilities may differ, a statistical test sensitive
      to changes of scale as well as to changes of location should be selected. Some
      references to such tests are given.

PMID- 11964208
TI  - Monoclonal antibody against human sperm-specific YLP12 peptide sequence involved
      in oocyte binding.
AB  - The monoclonalantibody (mAb) against YLP12 peptide was raised and its
      immunobiological properties were examined. In the Western blot procedure, the
      YLP12 mAb recognized a specific protein band of approximately 50 +/- 5 kD in
      human sperm extract and approximately 72 +/- 5 kD in human testis extract. The
      myeloma Ig control did not recognize these specific protein bands. In the
      immunofluorescence studies, the YLP12 mAb, and not the myeloma Ig, predominantly
      reacted with the acrosome regions of methanol-fixed human sperm. In the acrosome
      reaction assay, the YLP12 mAb showed a significant (p < .001) and a concentration
      dependent inhibition of acrosome reaction. The myeloma Ig did not affect the
      acrosome reaction. There was no apparent effect of antibodies on sperm motility.
      Thus, the monoclonal antibody, if humanized by genetic engineering technology,
      may provide a useful immunocontraceptive agent.

PMID- 11964209
TI  - Laboratory methods for the diagnosis of asthenozoospermia.
AB  - Human sperm samples from 46 men were evaluated for standard semen parameters by
      two trained technicians, according to WHO criteria. A computer-aided semen
      analyzer (CASA, HTM-IVOS) was employed. The overall mean coefficient of variation
      for the 2 participants and the 46 samples studied was 17% for the percentage of
      progressive motile spermatozoa (r = 0.77). Twenty-nine (63%) samples were
      classified as asthenozoospermia by both methods. From the studied samples, 12
      (26%) were classified as asthenozoospermia by the subjective method and 2 (4.3%)
      by CASA (p =.01). The two methods do not provide directly comparable data.

PMID- 11964210
TI  - Seminal plasma nitric oxide concentration in oligo- and/or asthenozoospermic
      subjects with/without varicocele.
AB  - There is an inverse correlation between seminal plasma nitric oxide (NO)
      concentration and sperm parameters (motility and concentration) in patients with
      varicocele. This study investigated whether this occurs in patients with oligo-
      and/or asthenozoospermia due to causes other than varicocele. A total of 69 (19
      with varicocele and oligo- and/or asthenozoospermia [group 1], 30 from oligo-
      and/or asthenozoospermic ones without varicocele [group 2], and 20 from healthy
      subjects [control group]) semen samples were analyzed. While group 1 had a
      significantly higher NO concentration in the seminal plasma compared to both the
      control group and group 2, there was no significant difference between group 2
      and the control group (p >.05). In group 1, but not in the other groups, there
      was an inverse correlation between the seminal plasma NO concentration and sperm
      motility and concentration. NO production could be specifically related to the
      varicocele, since NO production in oligo- and/or asthenozoospermia cases without
      varicocele is not increased.

PMID- 11964211
TI  - Varicocele in schoolboys.
AB  - This study was conducted to examine the effect of height and weight on the
      incidence of varicocele in schoolboys aged 5-16 years and the impact of
      varicocele on testicular size. Genital stage, height, weight, varicocele grade,
      and testicular size were recorded for 3047 school boys who were clinically
      examined while standing by a specialist in urology. Left varicocele was detected
      in 98 of the boys who were all aged 9-16 years. The mean weight of boys with and
      without varicocele was 42 kg (95% confidence interval [CI] 40-44 kg) and 47 (95%
      CI 47-47 kg), respectively (p =.00). There was no difference in mean height
      between the two groups nor in left and right testicular volume. Although 6 boys
      with varicocele had a left testicular volume > or =2 mL less than right, there
      were also 7 boys of comparable age who had a left testicular volume > or =2 mL
      larger than right. The incidence of varicocele in Greek adolescents is low. Boys
      with varicocele weighed significantly less but there were no significant
      differences in height or left versus right testicular volumes. In the light of
      these observations, the use of left testicular hypotrophy (> or =2 mL compared
      with the right testicle) should be reconsidered as an indicator for varicocele
      induced damage of the testicle in this age group.

PMID- 11964212
TI  - Compartmentalization of lysosomal enzymes in cauda epididymis of normal and
      castrated rats.
AB  - The mammalian epididymis is an organ particularly rich in acid hydrolases,
      consistent with a developed lysosomal apparatus. However, some of these enzymes
      could also play a role in an extracellular environment, since they are actively
      secreted by the epithelium. In this study the authors measured the activity of
      five acid hydrolases distributed between the epithelium, fluid, small vesicles,
      and spermatozoa of the rat cauda epididymis in adult rats, and compared with that
      distribution under conditions of deprivation of luminal testosterone and
      testicular compounds (hemicastration). Lysosomal enzymes are differently
      compartmentalized in rat cauda epididymis. Most of beta-galactosidase (beta-GAL)
      and aryl sulfatase (approximately 70%) were found in soluble form within the
      fluid. Some 60% of N-acetyl-beta-D-glucosaminidase (beta-NAG) and alpha
      mannosidase (alpha-MAN) become transiently bound to sperm, and beta-glucuronidase
      (beta-GLU) was mostly concentrated in the epithelium. After remotion of testis
      this distribution changed, as the retention of alpha-MAN, beta-GAL, beta-GLU, and
      beta-NAG by the epididiymal tissue increased. The increase of beta-GLU followed
      an increase of synthesis of the enzyme. The distribution of enzymes in the
      epididymis from the contralateral side was similar to that in normal rats. The
      different roles for each enzyme in the epididymis are discussed.

PMID- 11964213
TI  - DNA microarray analysis of genes involved in the process of differentiation in
      mouse Leydig cell line TTE1.
AB  - A Leydig cell line, TTE1, was established from the temperature-sensitive simian
      virus 40 large T-antigen transgenic mice. The cells showed temperature-sensitive
      growth characteristics and a differentiated phenotype at a nonpermissive
      temperature. To identify differentially expressed genes in the process of Leydig
      cell differentiation, the authors carried out microarray analysis of TTE1 cells
      cultured at permissive and nonpermissive temperatures. The resulting fluorescence
      labeled cDNAs synthesized from mRNAs were hybridized with Clontech's Atlas glass
      mouse 1.0 microarrays. Of the 1081 genes analyzed, the levels of 31 genes were
      changed, with 24 genes showing increased levels of expression and the remaining 7
      genes showing decreased levels. Tie2 was the most changed transcript, with a 13.5
      fold upregulation under the differentiated condition. The authors believe this to
      be the first report of broadscale gene expression in Leydig cell differentiation
      using the microarray technology. The ability to analyze broadscale gene
      expression in this manner provides a powerful tool for investigating the
      molecular mechanisms of Leydig cell functions.

PMID- 11964215
TI  - Induction of nuclear matrix-estradiol receptor complex during capacitation
      process in human spermatozoa.
AB  - Estrogen receptor levels were determined in capacitated and noncapacitated sperm
      cells of normospermic men by the charcoal dextran method. The estrogen receptor
      of the nuclear matrix was released using hypertonic solutions. The distribution
      of the estrogen receptor was higher by 30% in capacitated spermatozoa as related
      to noncapacitated spermatozoa. The values of estrogen receptors in capacitated
      and noncapacitated spermatozoa were 91 +/- 21 fmol/10(8) sperm cells and 26 +/- 7
      fmol/10(8) sperm cells, respectively. The association of estrogen receptor
      nuclear matrix may be an important factor in the regulation of the transcription
      of the sperm genome of capacitated spermatozoa during the pronuclei stage.

PMID- 11964214
TI  - Heparin-glutathione III: study with fluorescent probes as indicators of membrane
      status of bull sperm.
AB  - Sperm obtained from bull epididymes were used to validate in vitro the effect of
      heparin and reduced glutathione on sperm membrane status, with the use of sodium
      dodecyl sulfate (SDS) and Triton X-100 in the presence of propidium iodide (IP)
      and diacetate fluorescein (FDA). The metabolic activities of treated sperm were
      qualitatively monitored using an alamar Blue Redox fluorescence indicator.
      Heparin did not damage the sperm plasma membrane, whereas GSH and SDS at 26 h of
      incubation dissolved the plasma membrane and the acrosome. On the other hand, at
      time zero, Triton X-100 showed 75% of sperm stained with IP, indicating plasma
      membrane damage. Results validated by electron microscopy of thin sections of
      treated sperm showed complete lack of the membrane, acrosome, and postacrosomal
      membrane system with 0.01% Triton X-100. Extracellular 15 mM GSH completely
      disappeared the plasma membrane over the sperm nucleus, leaving the postacrosomal
      membrane system and nucleus without apparent damage. The metabolic activity was
      supported over 52 h of incubation in any of the incubation systems tested,
      including Triton X-100, which showed a spermaticide effect. The authors propose
      that membrane damage does not mean they are dead, no matter the vital stain
      employed, and also that FDA-IP staining can be used as a fluorescent marker of
      sperm plasmatic membrane permeabilization and nuclear swelling.

PMID- 11964216
TI  - Seminal plasma melatonin and gonadal steroids concentrations in normal men.
AB  - The authors determined semen quality and the concentrations of estradiol,
      testosterone, and melatonin in blood and seminal plasma of 8 normal men. To
      investigate the reproducibility of these parameters, semen analysis and hormone
      concentrations were determined on 3 occasions, 6 weeks apart. All 8 men had
      normal semen analysis. Blood melatonin (9.7-45.4 pg/mL) and testosterone (3.5
      12.3 ng/mL) levels were significantly higher than the comparable seminal plasma
      levels (0.6-5.0 pg/mL, p <.02; 0.1-0.9 ng/mL, p <.0001, respectively). Seminal
      plasma estradiol levels (46.9-91.3 pg/mL) were significantly higher than the
      blood levels (13.3-44.7 pg/mL) (p <.0001). The intraindividual variations in
      seminal plasma estradiol levels ranged between 8.7 and 13.8%. There was no
      correlation between sperm concentration, motility or morphology and blood or
      seminal plasma hormone levels. Also, blood and seminal plasma hormone levels were
      not correlated. These results indicate that in normospermic men seminal plasma
      estradiol levels are higher than blood hormone levels, suggesting local
      production of estradiol. This may imply that estrogen and/or the balance
      andorgen/estrogen is important in normal human spermatogenesis.

PMID- 11964217
TI  - Effects of dietary supplementation with fish oil, lard, or coconut oil on
      oxytocinase activity in the testis of mice.
AB  - Oxytocin (OT), locally synthesized in the testis, is involved in androgen
      biosynthesis. The use of polyunsaturated fatty acids (e.g., fish oil) in the diet
      may improve the fertilizing ability in mammals. Cystinyl aminopeptidase
      (oxytocinase) activity plays a major role regulating the functional status of OT.
      Sex steroids and the type of the fatty acid used in the diet modify
      aminopeptidase activities in serum. In the present study, the authors compared
      the effect of a fish oil supplemented diet with two other diets supplemented with
      saturated oils (lard and coconut) on oxytocinase activity in the testis of mice.
      The enzymatic activity was determined fluorometrically using cystinyl-beta
      naphthylamide as substrate. The results demonstrated higher levels of oxytocinase
      activity in mice fed the diet supplemented with fish oil than in those that were
      fed diets containing lard or coconut oils. The testicular functions in which OT
      is involved may be attenuated by the use of fish oil in the diet.

PMID- 11964219
TI  - Thermodynamic assessment of the stability of thrombin receptor antagonistic
      peptides in hydrophobic environments.
AB  - In this paper, a general procedure is described to determine thermodynamic
      parameters associated with the interaction of thrombin receptor antagonistic
      peptides (TRAPs) with immobilized nonpolar ligands. The results show that these
      interactions were associated with nonlinear van't Hoff dependencies over a wide
      temperature range. Moreover, changes in relevant thermodynamic parameters, namely
      the changes in Gibbs free energy of interaction, DeltaG(0)assoc, enthalpy of
      interaction, DeltaH(0)assoc, entropy of interaction, DeltaS(0)assoc, and heat
      capacity, DeltaC(0)p, have been related to the structural properties of these
      TRAP analogs. The implications of these investigations for the design of thrombin
      receptor agonists/antagonists with structures stabilized by intramolecular
      hydrophobic interactions are discussed.

PMID- 11964220
TI  - Role of constraint in catalysis and high-affinity binding by proteins.
AB  - Using a model for catalysis of a dynamic equilibrium, the role of constraint in
      catalysis is quantified. The intrinsic rigidity of proteins is shown to be
      insufficient to constrain the activated complexes of enzymes, irrespective of the
      mechanism. However, when minimization of the surface excess free energy of water
      surrounding a protein is considered, model proteins can be designed with regions
      of sufficient rigidity. Structures can be designed to focus surface tension or
      hydrophobic attraction as compressive stress. A monomeric structure has a limited
      ability to concentrate compressive stress and constrain activated complexes.
      Oligomeric or multidomain proteins, with domains surrounding a rigid core, have
      unlimited ability to concentrate stress, provided there are at least four
      domains. Under some circumstances, four is the optimum number, which could
      explain the frequency of tetrameric enzymes in nature. The minimum compressive
      stress in oligomers increases with the square of the radius. For tetramers of
      similar size to natural enzymes, this stress agrees reasonably well with that
      needed to constrain the activated complex. A similar principle applies to high
      affinity binding proteins. The models explain the trigonal pyramidal shape of
      fibroblast growth factor and provide a basis for interpretation of protein
      crystal structures.

PMID- 11964221
TI  - Molecular mechanism of H+ conduction in the single-file water chain of the
      gramicidin channel.
AB  - The conduction of protons in the hydrogen-bonded chain of water molecules (or
      "proton wire") embedded in the lumen of gramicidin A is studied with molecular
      dynamics free energy simulations. The process may be described as a "hop-and
      turn" or Grotthuss mechanism involving the chemical exchange (hop) of hydrogen
      nuclei between hydrogen-bonded water molecules arranged in single file in the
      lumen of the pore, and the subsequent reorganization (turn) of the hydrogen
      bonded network. Accordingly, the conduction cycle is modeled by two complementary
      steps corresponding respectively to the translocation 1) of an ionic defect (H+)
      and 2) of a bonding defect along the hydrogen-bonded chain of water molecules in
      the pore interior. The molecular mechanism and the potential of mean force are
      analyzed for each of these two translocation steps. It is found that the mobility
      of protons in gramicidin A is essentially determined by the fine structure and
      the dynamic fluctuations of the hydrogen-bonded network. The translocation of H+
      is mediated by spontaneous (thermal) fluctuations in the relative positions of
      oxygen atoms in the wire. In this diffusive mechanism, a shallow free-energy well
      slightly favors the presence of the excess proton near the middle of the channel.
      In the absence of H+, the water chain adopts either one of two polarized
      configurations, each of which corresponds to an oriented donor-acceptor hydrogen
      bond pattern along the channel axis. Interconversion between these two
      conformations is an activated process that occurs through the sequential and
      directional reorientation of water molecules of the wire. The effect of hydrogen
      bonding interactions between channel and water on proton translocation is
      analyzed from a comparison to the results obtained previously in a study of model
      nonpolar channels, in which such interactions were missing. Hydrogen-bond
      donation from water to the backbone carbonyl oxygen atoms lining the pore
      interior has a dual effect: it provides a coordination of water molecules well
      suited both to proton hydration and to high proton mobility, and it facilitates
      the slower reorientation or turn step of the Grotthuss mechanism by stabilizing
      intermediate configurations of the hydrogen-bonded network in which water
      molecules are in the process of flipping between their two preferred, polarized
      states. This mechanism offers a detailed molecular model for the rapid transport
      of protons in channels, in energy-transducing membrane proteins, and in enzymes.

PMID- 11964222
TI  - Simulations of membranes and other interfacial systems using P2(1) and Pc
      periodic boundary conditions.
AB  - We demonstrate the ease and utility of simulating heterogeneous interfacial
      systems with P2(1) and Pc periodic boundary conditions which allow, for example,
      lipids in a membrane to switch leaflets. In preliminary tests, P2(1) was shown to
      yield equivalent results to P1 in simulations of bulk water, a water/vacuum
      interface, and pure DPPC bilayers with an equal number of lipids per leaflet;
      equivalence of Pc and P1 was also demonstrated for the former two systems. P2(1)
      was further tested in simulations involving the spreading of an octane film on
      water, and equilibration of a DPPC bilayer from an initial condition containing
      different numbers of lipids in the two leaflets. Lastly, a simulation in P2(1) of
      a DOPC/melittin membrane showed significant passage of lipids to the melittin
      containing leaflet from the initial distribution, and lends insight into the
      condensation of lipids by melittin.

PMID- 11964223
TI  - Atomistic simulations of competition between substrates binding to an enzyme.
AB  - Although the idea that electrostatic potentials generated by enzymes can guide
      substrates to active sites is well established, it is not always appreciated that
      the same potentials can also promote the binding of molecules other than the
      intended substrate, with the result that such enzymes might be sensitive to the
      presence of competing molecules. To provide a novel means of studying such
      "electrostatic competition" effects, computer simulation methodology has been
      developed to allow the diffusion and association of many solute molecules around
      a single enzyme to be simulated. To demonstrate the power of the methodology,
      simulations have been conducted on an artificial fusion protein of citrate
      synthase (CS) and malate dehydrogenase (MDH) to assess the chances of
      oxaloacetate being channeled between the MDH and CS active sites. The simulations
      demonstrate that the probability of channeling is strongly dependent on the
      concentration of the initial substrate (malate) in the solution. In fact, the
      high concentrations of malate used in experiments appear high enough to abolish
      any channeling of oxaloacetate. The simulations provide a resolution of a serious
      discrepancy between previous simulations and experiments and raise important
      questions relating to the observability of electrostatically mediated substrate
      channeling in vitro and in vivo.

PMID- 11964224
TI  - Quantitative analysis of actin patch movement in yeast.
AB  - To investigate the mechanism of cortical actin patch movement in yeast, we
      implement a method for computer tracking the motion of the patches. Digital
      images from fluorescence microscope movies of living cells are fed into an image
      processing program, which generates two-dimensional patch coordinates in the
      plane of focus for each movie frame via an algorithm based on detection of rapid
      intensity variations. The patch coordinates in neighboring frames are connected
      by a minimum-distance algorithm. The method is used to analyze control cells and
      cells treated with the actin-depolymerizing agent latrunculin. The motion of the
      patches in both cases, as analyzed by mean-square patch displacements, is found
      to be a random walk on average, with a much lower diffusion coefficient for the
      latrunculin-treated cells. The mean-squared patch travel distances for all of the
      latrunculin-treated cells are lower than those for all of the control cells. The
      patches move independently of one another. We develop a quantitative criterion
      for the presence of directed motion, and show that numerous patches in the
      control cells display directed motion to a very high degree of certainty. A small
      number of patches in the latrunculin-treated cells display directed motion.

PMID- 11964225
TI  - A dynamical model of muscle activation, fatigue, and recovery.
AB  - A dynamical model is presented as a framework for muscle activation, fatigue, and
      recovery. By describing the effects of muscle fatigue and recovery in terms of
      two phenomenological parameters (F, R), we develop a set of dynamical equations
      to describe the behavior of muscles as a group of motor units activated by
      voluntary effort. This model provides a macroscopic view for understanding
      biophysical mechanisms of voluntary drive, fatigue effect, and recovery in
      stimulating, limiting, and modulating the force output from muscles. The model is
      investigated under the condition in which brain effort is assumed to be constant.
      Experimental validation of the model is performed by fitting force data measured
      from healthy human subjects during a 3-min sustained maximal voluntary handgrip
      contraction. The experimental results confirm a theoretical inference from the
      model regarding the possibility of maximal muscle force production, and suggest
      that only 97% of the true maximal force can be reached under maximal voluntary
      effort, assuming that all motor units can be recruited voluntarily. The effects
      of different motor unit types, time-dependent brain effort, sources of artifacts,
      and other factors that could affect the model are discussed. The applications of
      the model are also discussed.

PMID- 11964227
TI  - Radiolysis of lac repressor by gamma-rays and heavy ions: a two-hit model for
      protein inactivation.
AB  - Upon gamma-ray or argon ion irradiation of the lac repressor protein, its peptide
      chain is cleaved and the protein loses its lac operator-binding activity, as
      shown respectively by polyacrylamide gel electrophoresis and retardation gel
      electrophoresis. We developed phenomenological models that satisfactorily account
      for the experimental results: the peptide chain cleavage model considers that the
      average number of chain breaks per protomer is proportional to the irradiation
      dose and that the distribution of the number of breaks per protomer obeys
      Poisson's law. The repressor inactivation model takes into account the quaternary
      structure (a dimer of dimer) and the organization of the repressor in domains
      (two DNA binding sites, one per dimer). A protomer is inactivated by at least two
      different radiation-induced damages. A dimer is inactivated when at least one of
      the two protomers is inactivated. A tetramer is inactivated when both dimers are
      inactivated. From the combination of both models, we can deduce that chain
      cleavage cannot account for the protein inactivation, which should mainly result
      from oxidation of amino acid side chains. Indeed, particularly oxidizable and
      accessible amino acids (Tyr, His) are involved in the DNA binding process.

PMID- 11964226
TI  - Relating interactions between neurofilaments to the structure of axonal
      neurofilament distributions through polymer brush models.
AB  - Neurofilaments (NFs) have been proposed to interact with one another through
      mutual steric exclusion of their unstructured C-terminal "sidearm" domains,
      producing order in axonal NF distributions and conferring mechanical strength to
      the axon. Here we apply theory developed for polymer brushes to examine the
      relationship between the brush properties of the sidearms and NF organization in
      axons. We first measure NF-NF radial distribution functions and occupancy
      probability distributions for adult mice. Interpreting the probability
      distributions using information theory, we show that the NF distributions may be
      represented by a single pair potential of mean force. Then, to explore the
      relationship between model parameters and NF architecture, we conduct two
      dimensional Monte Carlo simulations of NF cross-sectional distributions. We
      impose purely repulsive interaction potentials in which the sidearms are
      represented as neutral and polyelectrolyte chains. By treating the NFs as
      telechelic polymer brushes, we also incorporate cross-bridging interactions. Both
      repulsive potentials are capable of reproducing NF cross-sectional densities and
      their pair correlations. We find that NF structure is sensitive to changes in
      brush thickness mediated by chain charge, consistent with the experimental
      observation that sidearm phosphorylation regulates interfilament spacing. The
      presence of attractive cross-bridging interactions contributes only modestly to
      structure for moderate degrees of cross-bridging and leads to NF aggregation for
      extensive cross-bridging.

PMID- 11964228
TI  - Shear flow-induced detachment kinetics of Dictyostelium discoideum cells from
      solid substrate.
AB  - Using Dictyostelium discoideum as a model organism of specific and nonspecific
      adhesion, we studied the kinetics of shear flow-induced cell detachment. For a
      given cell, detachment occurs for values of the applied hydrodynamic stress above
      a threshold. Cells are removed from the substrate with an apparent first-order
      rate constant that strongly depends on the applied stress. The threshold stress
      depends on cell size and physicochemical properties of the substrate, but is not
      affected by depolymerization of the actin and tubulin cytoskeleton. In contrast,
      the kinetics of cell detachment is almost independent of cell size, but is
      strongly affected by a modification of the substrate and the presence of an
      intact actin cytoskeleton. These results are interpreted in the framework of a
      peeling model. The threshold stress and the cell-detachment rate measure the
      local equilibrium energy and the dissociation rate constant of the adhesion
      bridges, respectively.

PMID- 11964229
TI  - Estimation of the sarcoplasmic reticulum Ca2+ release flux underlying Ca2+
      sparks.
AB  - Using a combination of experimental and numerical approaches, we have tested two
      different approaches to calculating the sarcoplasmic reticulum (SR) Ca2+ release
      flux, which gives rise to cardiac muscle Ca2+ sparks. By using two-photon excited
      spot photolysis of DM-Nitrophen, known Ca2+ release flux time courses were
      generated to provide the first experimental validation of spark flux
      reconstruction algorithms. These artificial Ca2+ sparks show that it is possible
      to calculate the SR Ca2+ release waveform with reasonable accuracy, provided the
      flux equations reasonably reflect the properties of the experimental system.
      Within cardiac muscle cells, we show that Ca2+ flux reconstruction is complicated
      by the substantial dye binding to proteins, a factor that has not been adequately
      addressed in previous flux reconstruction algorithms. Furthermore, our numerical
      experiments suggest that the calculated time course of release flux inactivation
      based on conventional flux reconstruction algorithms is likely to be in error. We
      therefore developed novel algorithms based on an explicit dye binding scheme.
      When these algorithm were applied to evoked Ca2+ sparks in rat cardiac
      ventricular myocytes, the reconstructed Ca2+ release waveform peaked in ~5 ms and
      decayed with a halftime of approximately 5 ms. The peak flux magnitude was 7-12
      pA, suggesting that sparks must arise from clusters of >15 ryanodine receptors.

PMID- 11964230
TI  - Preformed oligomeric epidermal growth factor receptors undergo an ectodomain
      structure change during signaling.
AB  - Fluorescence resonance energy transfer (FRET) was used to reveal aspects of the
      mechanism of signal transduction by epidermal growth factor receptors (EGFR). The
      superpositions of epidermal growth factor (EGF), transforming growth factor-alpha
      (TGFalpha) and an antibody fragment (29.1) to the carbohydrate extremity of the
      receptor's ectodomain as measured by FRET, show that 14% of EGFRs in A431 cells
      are oligomerized before growth factor binding. After binding growth factor and
      signaling, these oligomers dissociate before releasing growth factor. Time
      courses of the FRET-derived distances between constitutively oligomerized EGFRs
      during signal transduction show a transient structural change in the
      extracellular domain, which occurs simultaneously with the production of
      intracellular Ca2+ signals. The FRET measurements also show a slow increase in
      oligomerization of EGFR monomers after growth factor binding. The structural
      change found in the extracellular domain of oligomeric EGFRs is similar to that
      shown by others for EPO, Neu, Fas, and tumor necrosis factor receptors, and may
      therefore be a common property of the transduction of the receptor-mediated
      signals.

PMID- 11964231
TI  - Ca2+ activation of RyR1 is not necessary for the initiation of skeletal-type
      excitation-contraction coupling.
AB  - Although an elevation in myoplasmic Ca2+ can activate the skeletal muscle
      ryanodine receptor (RyR1), the function of this Ca2+ activation is unclear
      because extracellular Ca2+ influx is unnecessary for skeletal-type EC coupling.
      To determine whether Ca2+ activation of RyR1 is necessary for the initiation of
      skeletal-type EC coupling, we examined the behavior of RyR1 with glutamate 4032
      mutated to alanine (E4032A-RyR1) because this mutation had been shown to
      dramatically reduce activation by Ca2+. Proc. Natl. Acad. Sci. USA. 98:2865
      2870). Analysis after reconstitution into planar lipid bilayers revealed that
      E4032A-RyR1 was negligibly activated by 100 microM Ca2+ (P(o) too low to be
      measured). Even in the presence of both 2 mM caffeine and 2 mM ATP, P(o) remained
      low for E4032A-RyR1 (ranging from <0.0001 in 100 microM free Ca2+ to 0.005 in 2
      mM free Ca2+). Thus, the E4032A mutation caused a nearly complete suppression of
      activation of RyR1 by Ca2+. Depolarization of E4032A-RyR1-expressing myotubes
      elicited L-type Ca2+ currents of approximately normal size and myoplasmic Ca2+
      transients that were skeletal-type, but about fivefold smaller than those for
      wild-type RyR1. The reduced amplitude of the Ca2+ transient is consistent either
      with the possibility that Ca2+ activation amplifies Ca2+ release during EC
      coupling, or that the E4032A mutation generally inhibits activation of RyR1. In
      either case, Ca2+ activation of RyR1 does not appear to be necessary for the
      initiation of Ca2+ release during EC coupling in skeletal muscle.

PMID- 11964232
TI  - Role of the proposed pore-forming segment of the Ca2+ release channel (ryanodine
      receptor) in ryanodine interaction.
AB  - In earlier studies we showed that point mutations introduced into the proposed
      pore-forming segment, GVRAGGGIGD (amino acids 4820-4829), of the mouse cardiac
      ryanodine receptor reduced or abolished high affinity [3H]ryanodine binding. Here
      we investigate the effects of these mutations on the affinity and dissociation
      properties of [3H]ryanodine binding and on ryanodine modification of the
      ryanodine receptor channel at the single channel and whole cell levels. Scatchard
      analysis and dissociation studies reveal that mutation G4824A decreases the
      equilibrium dissociation constant (K(d)) and the dissociation rate constant
      (k(off)), whereas mutations G4828A and D4829A increase the K(d) and k(off)
      values. The effect of ryanodine on single G4828A and D4829A mutant channels is
      reversible on the time scale of single channel experiments, in contrast to the
      irreversible effect of ryanodine on single wild-type channels. Ryanodine alone is
      able to induce a large and sustained Ca2+ release in HEK293 cells transfected
      with the R4822A or G4825A mutant cDNA at the resting cytoplasmic Ca2+ but causes
      little or no Ca2+ release in cells transfected with the wild-type cDNA. Mutation
      G4826C diminishes the functional effect of ryanodine on Ca2+ release but spares
      caffeine-induced Ca2+ release in HEK293 cells. Co-expression of the wild-type and
      G4826C mutant proteins produces single channels that interact with ryanodine
      reversibly and display altered conductance and ryanodine response. These results
      are consistent with the view that the proposed pore-forming segment is a critical
      determinant of ryanodine interaction. A putative model of ryanodine-ryanodine
      receptor interaction is proposed.

PMID- 11964233
TI  - Steady-state and closed-state inactivation properties of inactivating BK
      channels.
AB  - Calcium-dependent potassium (BK-type) Ca2+ and voltage-dependent K+ channels in
      chromaffin cells exhibit an inactivation that probably arises from coassembly of
      Slo1 alpha subunits with auxiliary beta subunits. One goal of this work was to
      determine whether the Ca2+ dependence of inactivation arises from any mechanism
      other than coupling of inactivation to the Ca2+ dependence of activation. Steady
      state inactivation and the onset of inactivation were studied in inside-out
      patches and whole-cell recordings from rat adrenal chromaffin cells with parallel
      experiments on inactivating BK channels resulting from cloned alpha + beta2
      subunits. In both cases, steady-state inactivation was shifted to more negative
      potentials by increases in submembrane [Ca2+] from 1 to 60 microM. At 10 and 60
      microM Ca2+, the maximal channel availability at negative potentials was similar
      despite a shift in the voltage of half availability, suggesting there is no
      strictly Ca2+-dependent inactivation. In contrast, in the absence of Ca2+,
      depolarization to potentials positive to +20 mV induces channel inactivation.
      Thus, voltage-dependent, but not solely Ca2+-dependent, kinetic steps are
      required for inactivation to occur. Finally, under some conditions, BK channels
      are shown to inactivate as readily from closed states as from open states,
      indicative that a key conformational change required for inactivation precedes
      channel opening.

PMID- 11964234
TI  - Site-directed mutagenesis of tyrosine 118 within the central constriction site of
      the LamB (Maltoporin) channel of Escherichia coli. I. Effect on ion transport.
AB  - The three-dimensional structure of the malto-oligosaccharide-specific LamB
      channel of Escherichia coli (also called maltoporin) is known from x-ray
      crystallography. The central constriction of the channel formed by the external
      loop 3 is controlled by a tyrosine residue (Y118). Y118 was replaced by site
      directed mutagenesis by ten other amino acids (alanine, isoleucine, asparagine,
      serine, cysteine, aspartic acid, arginine, histidine, phenylalanine, and
      tryptophane) including neutral ones, negatively and positively charged amino
      acids to study the effect of their size, hydrophobicity, and charge on ion
      transport through LamB. The mutant proteins were purified to homogeneity. They
      were reconstituted into lipid bilayer membranes and single-channel conductance
      and ion selectivity were measured to get insight into the mechanism of ion
      transport through LamB. The mutation of Y118 to any other nonaromatic amino acid
      led to a substantial increase of the single-channel conductance by more than a
      factor of six at maximum. The highest effect was observed for Y118D.
      Additionally, a nonlinear relationship between the salt concentration in the
      aqueous phase and the channel conductance was observed for this mutant,
      indicating strong discrete charge effects on ion conductance. For all other
      mutants, with the exception of Y118R, linear relationships were found between
      single-channel conductance and bulk aqueous concentration. The individual
      hydrophobicity indices of the amino acids introduced inside the central
      constriction of the LamB channel had a somewhat smaller effect on the single
      channel conductance as compared with the effect of their size and charge.

PMID- 11964235
TI  - Implications of threonine hydrogen bonding in the glycophorin A transmembrane
      helix dimer.
AB  - The transmembrane helix of glycophorin A contains a seven-residue motif,
      LIxxGVxxGVxxT, that mediates protein dimerization. Threonine is the only polar
      amino acid in this motif with the potential to stabilize the dimer through
      hydrogen-bonding interactions. Polarized Fourier transform infrared spectroscopy
      is used to establish a robust protocol for incorporating glycophorin A
      transmembrane peptides into membrane bilayers. Analysis of the dichroic ratio of
      the 1655-cm(-1) amide I vibration indicates that peptides reconstituted by
      detergent dialysis have a transmembrane orientation with a helix crossing angle
      of <35 degrees. Solid-state nuclear magnetic resonance spectroscopy is used to
      establish high resolution structural restraints on the conformation and packing
      of Thr-87 in the dimer interface. Rotational resonance measurement of a 2.9-A
      distance between the gamma-methyl and backbone carbonyl carbons of Thr-87 is
      consistent with a gauche- conformation for the chi1 torsion angle. Rotational
      echo double-resonance measurements demonstrate close packing (4.0 +/- 0.2 A) of
      the Thr-87 gamma-methyl group with the backbone nitrogen of Ile-88 across the
      dimer interface. The short interhelical distance places the beta-hydroxyl of Thr
      87 within hydrogen-bonding range of the backbone carbonyl of Val-84 on the
      opposing helix. These results refine the structure of the glycophorin A dimer in
      membrane bilayers and highlight the complementary role of small and polar
      residues in the tight association of transmembrane helices in membrane proteins.

PMID- 11964236
TI  - SANS study on the effect of lanthanide ions and charged lipids on the morphology
      of phospholipid mixtures. Small-angle neutron scattering.
AB  - The structural phase behavior of phospholipid mixtures consisting of short-chain
      (dihexanoyl phosphatidylcholine) and long-chain lipids (dimyristoyl
      phosphatidylcholine and dimyristoyl phosphatidylglycerol), with and without
      lanthanide ions was investigated by small-angle neutron scattering (SANS). SANS
      profiles were obtained from 10 degrees C to 55 degrees C using lipid
      concentrations ranging from 0.0025 g/ml to 0.25 g/ml. The results reveal a wealth
      of distinct morphologies, including lamellae, multi-lamellar vesicles,
      unilamellar vesicles, and bicellar disks.

PMID- 11964237
TI  - An innovative procedure using a sublimable solid to align lipid bilayers for
      solid-state NMR studies.
AB  - Uniaxially aligned phospholipid bilayers are often used as model membranes to
      obtain structural details of membrane-associated molecules, such as peptides,
      proteins, drugs, and cholesterol. Well-aligned bilayer samples can be difficult
      to prepare and no universal procedure has been reported that orients all
      combinations of membrane-embedded components. In this study, a new method for
      producing mechanically aligned phospholipid bilayer samples using naphthalene, a
      sublimable solid, was developed. Using (31)P-NMR spectroscopy, comparison of a
      conventional method of preparing mechanically aligned samples with the new
      naphthalene procedure found that the use of naphthalene significantly enhanced
      the alignment of 3:1 1-palmitoyl-2-oleoyl-phosphatidylethanolamine to 1-palmitoyl
      2-oleoyl-phosphatidylglycerol. The utility of the naphthalene procedure is also
      demonstrated on bilayers of many different compositions, including bilayers
      containing peptides such as pardaxin and gramicidin. These results show that the
      naphthalene procedure is a generally applicable method for producing mechanically
      aligned samples for use in NMR spectroscopy. The increase in bilayer alignment
      implies that this procedure will improve the sensitivity of solid-state NMR
      experiments, in particular those techniques that detect low-sensitivity nuclei,
      such as 15N and 13C.

PMID- 11964238
TI  - Determination of L(alpha)-H(II) phase transition temperature for 1,2-dioleoyl-sn
      glycero-3-phosphatidylethanolamine.
AB  - The thermodynamic properties of fully-hydrated lipids provide important
      information about the stability of membranes and the energetic interactions of
      lipid bilayers with membrane proteins (Nagle and Scott, Physics Today, 2:39,
      1978). The lamellar/inverse hexagonal (L(alpha)-H(II)) phase transition of 1,2
      dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) water mixtures is a first
      order transition and, therefore, at constant pressure, must have a
      thermodynamically well-defined equilibrium transition temperature. The observed
      transition temperature is known to be dependent upon the rate at which the
      temperature is changed, which accounts for the many different values in the
      literature. X-ray diffraction was used to study the phase transition of fully
      hydrated DOPE to determine the rate-independent transition temperature, T(LH).
      Samples were heated or cooled for a range of rates, 0.212 < r < 225 degrees C/hr,
      and the rate-dependent apparent phase transition temperatures, T(A)(r) were
      determined from the x-ray data. By use of a model-free extrapolation method, the
      transition temperature was found to be T(LH) = 3.33 +/- 0.16 degrees C. The
      hysteresis, /T(A)(r) - T(LH)/, was identical for heating and cooling rates, +/-r,
      and varied as /r/beta for beta approximately 1/4. This unexpected power-law
      relationship is consistent with a previous study (Tate et al., Biochemistry,
      31:1081-1092, 1992) but differs markedly from the exponential behavior of
      activation barrier kinetics. The methods used in this study are general and
      provide a simple way to determine the true mesomorphic phase transition
      temperatures of other lipid and lyotropic systems.

PMID- 11964239
TI  - Constant normal pressure, constant surface tension, and constant temperature
      molecular dynamics simulation of hydrated 1,2-dilignoceroylphosphatidylcholine
      monolayer.
AB  - A constant normal pressure, constant surface tension, and constant temperature
      (NP(N)gammaT) molecular dynamics (MD) simulation of the liquid condensed phase of
      a 1,2-dilignoceroylphosphatidylcholine (DLGPC) monolayer has been performed at
      293.15 K. A DLGPC molecule has two saturated 24-carbon acyl chains, giving the
      hydrocarbon core thickness of the monolayer approximately 28 A, which is close to
      the hydrocarbon core thickness of a membrane of a living system. NP(N)gammaT
      ensemble was used to reproduce the experimental observations, such as area/lipid,
      because surface tension is an essential factor in determining the monolayer
      structure. Data analysis on DLGPC/water monolayer shows that various liquid
      condensed-phase properties of the monolayer have been well reproduced from the
      simulation, indicating that surface tension 22.9 mN/M used in the simulation is
      an appropriate condition for the condensed-phase NP(N)gammaT simulation. The
      simulation results suggest that this long-chain phospholipid monolayer shares
      many structural characteristics with typical short-chain 1,2
      diacylphosphatidylcholine systems, such as DPPC/water monolayer in the condensed
      phase and DPPC/water bilayer in the gel phase. Furthermore, it was found that
      DLGPC/water monolayer has almost completely rotationally disordered acyl chains,
      which have not been observed so far in short-chain 1,2
      diacylphosphatidylcholine/water bilayers. This study indicates the good
      biological relevance of the DLGPC/water monolayer which might be useful in
      protein/lipid studies to reveal protein structure and protein/lipid interactions
      in a membrane environment.

PMID- 11964240
TI  - Size distribution of barrel-stave aggregates of membrane peptides: influence of
      the bilayer lateral pressure profile.
AB  - Some membrane peptides, such as Alamethicin, form barrel-stave aggregates with a
      broad probability distribution of size (number of peptides in the aggregate).
      This distribution has been shown to depend on the characteristics of the lipid
      bilayer. A mechanism for this influence is suggested, in analogy to earlier work
      on the effects of changes in bilayer composition on conformational equilibria in
      membrane proteins, that is based on coupling of shifts in the distribution of
      lateral pressures in the bilayer to depth-dependent changes in the lateral
      excluded area that accompanies the formation of an aggregate. Thermodynamic
      analysis is coupled with a simple geometric model of aggregates of kinked
      cylindrical peptides and with results of previously calculated lateral pressure
      distributions to predict the effects of changes in bilayer characteristics on
      aggregate size distributions, in qualitative agreement with experimental results.

PMID- 11964241
TI  - The size of lipid rafts: an atomic force microscopy study of ganglioside GM1
      domains in sphingomyelin/DOPC/cholesterol membranes.
AB  - Atomic force microscopy has been used to study the distribution of ganglioside
      GM1 in model membranes composed of ternary lipid mixtures that mimic the
      composition of lipid rafts. The results demonstrate that addition of 1% GM1 to
      1:1:1 sphingomyelin/dioleoylphosphatidylcholine/cholesterol monolayers leads to
      the formation of small ganglioside-rich microdomains (40-100 nm in size) that are
      localized preferentially in the more ordered sphingomyelin/cholesterol-rich
      phase. With 5% GM1 some GM1 microdomains are also detected in the
      dioleoylphosphatidylcholine-rich phase. A similar preferential localization of
      GM1 in the ordered phase is observed for bilayers with the same ternary lipid
      mixture in the upper leaflet. The small GM1-rich domains observed in these
      experiments are similar to the sizes for lipid rafts in natural membranes but
      considerably smaller than the ordered bilayer domains that have been shown to be
      enriched in GM1 in recent fluorescence microscopy studies of lipid bilayers. The
      combined data from a number of studies of model membranes indicate that lateral
      organization occurs on a variety of length scales and mimics many of the
      properties of natural membranes.

PMID- 11964242
TI  - Structural features of cross-bridges in isometrically contracting skeletal
      muscle.
AB  - Two-dimensional x-ray diffraction was used to investigate structural features of
      cross-bridges that generate force in isometrically contracting skeletal muscle.
      Diffraction patterns were recorded from arrays of single, chemically skinned
      rabbit psoas muscle fibers during isometric force generation, under relaxation,
      and in rigor. In isometric contraction, a rather prominent intensification of the
      actin layer lines at 5.9 and 5.1 nm and of the first actin layer line at 37 nm
      was found compared with those under relaxing conditions. Surprisingly, during
      isometric contraction, the intensity profile of the 5.9-nm actin layer line was
      shifted toward the meridian, but the resulting intensity profile was different
      from that observed in rigor. We particularly addressed the question whether the
      differences seen between rigor and active contraction might be due to a rigor
      like configuration of both myosin heads in the absence of nucleotide (rigor),
      whereas during active contraction only one head of each myosin molecule is in a
      rigor-like configuration and the second head is weakly bound. To investigate this
      question, we created different mixtures of weak binding myosin heads and rigor
      like actomyosin complexes by titrating MgATPgammaS at saturating [Ca2+] into
      arrays of single muscle fibers. The resulting diffraction patterns were different
      in several respects from patterns recorded under isometric contraction,
      particularly in the intensity distribution along the 5.9-nm actin layer line.
      This result indicates that cross-bridges present during isometric force
      generation are not simply a mixture of weakly bound and single-headed rigor-like
      complexes but are rather distinctly different from the rigor-like cross-bridge.
      Experiments with myosin-S1 and truncated S1 (motor domain) support the idea that
      for a force generating cross-bridge, disorder due to elastic distortion might
      involve a larger part of the myosin head than for a nucleotide free, rigor cross
      bridge.

PMID- 11964243
TI  - Measurement of thin filament lengths by distributed deconvolution analysis of
      fluorescence images.
AB  - The lengths of the actin (thin) filaments in sarcomeres directly influence the
      physiological properties of striated muscle. Although electron microscopy
      techniques provide the highest precision and accuracy for measuring thin filament
      lengths, significant obstacles limit their widespread use. Here, we describe
      distributed deconvolution, a fluorescence-based method that determines the
      location of specific thin filament components such as tropomodulin (Tmod) or
      probes such as phallacidin (a phalloidin derivative). Using Tmod and phallacidin
      fluorescence, we were able to determine the thin filament lengths of isolated
      chicken pectoralis major myofibrils with an accuracy and precision comparable to
      electron microscopy. Additionally, phallacidin fluorescence intensity at the Z
      line provided information about the width of Z lines. Furthermore, we detected
      significant variations in thin filaments lengths among individual myofibrils from
      chicken posterior latissimus dorsai and embryonic chick cardiac myocytes,
      suggesting that a ruler molecule (e.g., nebulin) does not strictly determine thin
      filament lengths in these muscles. This versatile method is applicable to
      myofibrils in living cells that exhibit significant variation in sarcomere
      lengths, and only requires a fluorescence microscope and a CCD camera.

PMID- 11964244
TI  - Optimal range for parvalbumin as relaxing agent in adult cardiac myocytes: gene
      transfer and mathematical modeling.
AB  - Parvalbumin (PV) has recently been shown to increase the relaxation rate when
      expressed in intact isolated cardiac myocytes via adenovirus gene transfer. We
      report here a combined experimental and mathematical modeling approach to
      determine the dose-response and the sarcomere length (SL) shortening-frequency
      relationship of PV in adult rat cardiac myocytes in primary culture. The dose
      response was obtained experimentally by observing the PV-transduced myocytes at
      different time points after gene transfer. Calcium transients and unloaded
      mechanical contractions were measured. The results were as follows. At low
      estimated [PV] (approximately 0.01 mM), contractile parameters were unchanged; at
      intermediate [PV], relaxation rate of the mechanical contraction and the decay
      rate of the calcium transient increased with little effects on amplitude; and at
      high [PV] (approximately 0.1 mM), relaxation rate was further increased, but the
      amplitudes of the mechanical contraction and the calcium transient were
      diminished when compared with control myocytes. The SL shortening-frequency
      relationship exhibited a biphasic response to increasing stimulus frequency in
      controls (decrease in amplitude and re-lengthening time from 0.2 to 1.0 Hz
      followed by an increase in these parameters from 2.0 to 4.0 Hz). The effect of PV
      was to flatten this frequency response. This flattening effect was partly
      explained by a reduction in the variation in fractional binding of PV to calcium
      during beats at high frequency. In conclusion, experimental results and
      mathematical modeling indicate that there is an optimal PV range for which
      relaxation rate is increased with little effect on contractile amplitude and that
      PV effectiveness decreases as the stimulus frequency increases.

PMID- 11964245
TI  - Tropomyosin requires an intact N-terminal coiled coil to interact with
      tropomodulin.
AB  - Tropomodulins (Tmods) are tropomyosin (TM) binding proteins that bind to the
      pointed end of actin filaments and modulate thin filament dynamics. They bind to
      the N termini of both "long" TMs (with the N terminus encoded by exon 1a of the
      alpha-TM gene) and "short" nonmuscle TMs (with the N terminus encoded by exon
      1b). In this present study, circular dichroism was used to study the interaction
      of two designed chimeric proteins, AcTM1aZip and AcTM1bZip, containing the N
      terminus of a long or a short TM, respectively, with protein fragments containing
      residues 1 to 130 of erythrocyte or skeletal muscle Tmod. The binding of either
      TMZip causes similar conformational changes in both Tmod fragments promoting
      increases in both alpha-helix and beta-structure, although they differ in binding
      affinity. The circular dichroism changes in the Tmod upon binding and modeling of
      the Tmod sequences suggest that the interface between TM and Tmod includes a
      three- or four-stranded coiled coil. An intact coiled coil at the N terminus of
      the TMs is essential for Tmod binding, as modifications that disrupt the N
      terminal helix, such as removal of the N-terminal acetyl group from AcTM1aZip or
      striated muscle alpha-TM, or introduction of a mutation that causes nemaline
      myopathy, Met-8-Arg, into AcTM1aZip destroyed Tmod binding.

PMID- 11964247
TI  - Time-resolved X-ray diffraction reveals movement of F helix of D96N
      bacteriorhodopsin during M-MN transition at neutral pH.
AB  - D96N bacteriorhodopsin has two photointermediates with the deprotonated Schiff
      base: the M and MN intermediates. We measure the time-resolved x-ray diffraction
      of the D96N purple membrane after flash photoexcitation (pH 7.0, 25 degrees C).
      The data clearly show the M-MN transition during the D96N photocycle. Low
      resolution projection maps of these states show that the F helix of the MN
      intermediate shifts from its original position and this shift is much larger than
      that of the M intermediate. This indicates that the F helix moves in the M-MN
      transition of the D96N bacteriorhodopsin photocycle. Moreover, the existence of
      the MN intermediate in the D96N photocycle under neutral pH indicates that the MN
      intermediate is not peculiar to the alkaline condition. It is notable that the
      structural transition of M-MN is independent of the protonation state of the
      Schiff base. Therefore, the F helix movement precedes reprotonation of the Schiff
      base in the bacteriorhodopsin photocycle. Our previous study showed that the M-MN
      transition is hydration-dependent and that the MN intermediate is more hydrated
      than the M intermediate. Considering this together with the present results, we
      conclude that the movement of the F helix causes hydration of the cytoplasmic
      side, which promotes the reprotonation of the Schiff base.

PMID- 11964246
TI  - Critical effect of the N2 amino group on structure, dynamics, and elasticity of
      DNA polypurine tracts.
AB  - Unrestrained 5-20-ns explicit-solvent molecular dynamics simulations using the
      Cornell et al. force field have been carried out for d[GCG(N)11GCG]2 (N, purine
      base) considering guanine*cytosine (G*C), adenine*thymine (A*T), inosine*5-methyl
      cytosine (I*mC), and 2-amino-adenine*thymine (D*T) basepairs. The simulations
      unambiguously show that the structure and elasticity of N-tracts is primarily
      determined by the presence of the amino group in the minor groove. Simulated A-,
      I-, and AI-tracts show almost identical structures, with high propeller twist and
      minor groove narrowing. G- and D-tracts have small propeller twisting and are
      partly shifted toward the A-form. The elastic properties also differ between the
      two groups. The sequence-dependent electrostatic component of base stacking seems
      to play a minor role. Our conclusions are entirely consistent with available
      experimental data. Nevertheless, the propeller twist and helical twist in the
      simulated A-tract appear to be underestimated compared to crystallographic
      studies. To obtain further insight into the possible force field deficiencies,
      additional multiple simulations have been made for d(A)10, systematically
      comparing four major force fields currently used in DNA simulations and utilizing
      B and A-DNA forms as the starting structure. This comparison shows that the
      conclusions of the present work are not influenced by the force field choice.

PMID- 11964248
TI  - Light-induced hydrolysis and rebinding of nonisomerizable bacteriorhodopsin
      pigment.
AB  - Bacteriorhodopsin (bR) is characterized by a retinal-protein protonated Schiff
      base covalent bond, which is stable for light absorption. We have revealed a
      light-induced protonated Schiff base hydrolysis reaction in a 13-cis locked bR
      pigment (bR5.13; lambda(max) = 550 nm) in which isomerization around the critical
      C13==C14 double bond is prevented by a rigid ring structure. The photohydrolysis
      reaction takes place without isomerization around any of the double bonds along
      the polyene chain and is indicative of protein conformational alterations
      probably due to light-induced polarization of the retinal chromophore. Two
      photointermediates are formed during the hydrolysis reaction, H450 (lambda(max) =
      450 nm) and H430 (lambda(max) = 430 nm), which are characterized by a 13-cis
      configuration as analyzed by high-performance liquid chromatography. Upon blue
      light irradiation after the hydrolysis reaction, these intermediates rebind to
      the apomembrane to reform bR5.13. Irradiation of the H450 intermediate forms the
      original pigment, whereas irradiation of H430 at neutral pH results in a red
      shifted species (P580), which thermally decays back to bR5.13. Electron
      paramagnetic resonance (EPR) spectroscopy indicates that the cytoplasmic side of
      bR5.13 resembles the conformation of the N photointermediate of native bR.
      Furthermore, using osmotically active solutes, we have observed that the
      hydrolysis rate is dependent on water activity on the cytoplasmic side. Finally,
      we suggest that the hydrolysis reaction proceeds via the reversed pathway of the
      binding process and allows trapping a new intermediate, which is not accumulated
      in the binding process.

PMID- 11964249
TI  - First evidence for phototropin-related blue-light receptors in prokaryotes.
AB  - A prokaryotic protein, YtvA from Bacillus subtilis, was found to possess a light,
      oxygen, voltage (LOV) domain sharing high homology with the photoactive, flavin
      mononucleotide (FMN)-binding LOV domains of phototropins (phot), blue-light
      photoreceptors for phototropism in higher plants. Computer-based three
      dimensional modeling suggests that YtvA-LOV binds FMN in a similar pocket as phot
      LOVs. Recombinant YtvA indeed exhibits the same spectroscopical features and blue
      light-induced photochemistry as phot-LOVs, with the reversible formation of a
      blue-shifted photoproduct, assigned to an FMN-cysteine thiol adduct (Thio383). By
      means of laser-flash photolysis and time-resolved optoacoustic experiments, we
      measured the quantum yield of formation for Thio383, Phi(Thio) = 0.49, and the
      enthalpy change, DeltaH(Thio) = 135 kJ/mol, with respect to the parent state. The
      formation of Thio383 is accompanied by a considerable volume contraction,
      DeltaV(Thio) = -13.5 ml/mol. Similar to phot-LOVs, Thio383 is formed from the
      decay of a red-shifted transient species, T650, within 2 micros. In both YtvA and
      free FMN, this transient has an enthalpy content of approximately 200 kJ/mol, and
      its formation is accompanied by a small contraction, DeltaV(T) approximately -1.5
      ml/mol, supporting the assignment of T650 to the FMN triplet state, as suggested
      by spectroscopical evidences. These are the first studies indicating that
      phototropin-related, blue-light receptors may exist also in prokaryotes, besides
      constituting a steadily growing family in plants.

PMID- 11964250
TI  - Comparative Fourier transform infrared spectroscopy study of cold-, pressure-,
      and heat-induced unfolding and aggregation of myoglobin.
AB  - We studied the cold unfolding of myoglobin with Fourier transform infrared
      spectroscopy and compared it with pressure and heat unfolding. Because protein
      aggregation is a phenomenon with medical as well as biotechnological
      implications, we were interested in both the structural changes as well as the
      aggregation behavior of the respective unfolded states. The cold- and pressure
      induced unfolding both yield a partially unfolded state characterized by a
      persistent amount of secondary structure, in which a stable core of G and H
      helices is preserved. In this respect the cold- and pressure-unfolded states show
      a resemblance with an early folding intermediate of myoglobin. In contrast, the
      heat unfolding results in the formation of the infrared bands typical of
      intermolecular antiparallel beta-sheet aggregation. This implies a transformation
      of alpha-helix into intermolecular beta-sheet. H/2H-exchange data suggest that
      the helices are first unfolded and then form intermolecular beta-sheets. The
      pressure and cold unfolded states do not give rise to the intermolecular
      aggregation bands that are typical for the infrared spectra of many heat-unfolded
      proteins. This suggests that the pathways of the cold and pressure unfolding are
      substantially different from that of the heat unfolding. After return to ambient
      conditions the cold- or pressure-treated proteins adopt a partially refolded
      conformation. This aggregates at a lower temperature (32 degrees C) than the
      native state (74 degrees C).

PMID- 11964251
TI  - Studies of Pseudomonas aeruginosa azurin mutants: cavities in beta-barrel do not
      affect refolding speed.
AB  - Pseudomonas aeruginosa azurin is a blue-copper protein with a Greek-key fold.
      Removal of copper produces an apoprotein with the same structure as holoazurin.
      To address the effects on thermodynamic stability and folding dynamics caused by
      small cavities in a beta-barrel, we have studied the behavior of the apo-forms of
      wild-type and two mutant (His-46-Gly and His-117-Gly) azurins. The equilibrium-
      and kinetic-folding and unfolding reactions appear as two-state processes for all
      three proteins. The thermodynamic stability of the two mutants is significantly
      decreased as compared with the stability of wild-type azurin, in accord with
      cavities in or near the hydrophobic interior having an overall destabilizing
      effect. Large differences are also found in the unfolding rates: the mutants
      unfold much faster than wild-type azurin. In contrast, the folding-rate constants
      are almost identical for the three proteins and closely match the rate-constant
      predicted from the native-state topology of azurin. We conclude that the topology
      is more important than equilibrium stability in determining the folding speed of
      azurin.

PMID- 11964253
TI  - Proteins wriggle.
AB  - We propose an algorithmic strategy for improving the efficiency of Monte Carlo
      searches for the low-energy states of proteins. Our strategy is motivated by a
      model of how proteins alter their shapes. In our model, when proteins fold under
      physiological conditions, their backbone dihedral angles change synchronously in
      groups of four or more to avoid steric clashes and respect the kinematic
      conservation laws. They wriggle; they do not thrash. We describe a simple
      algorithm that can be used to incorporate wriggling in Monte Carlo simulations of
      protein folding. We have tested this wriggling algorithm against a code in which
      the dihedral angles are varied independently (thrashing). Our standard of success
      is the average root-mean-square distance (rmsd) between the alpha-carbons of the
      folding protein and those of its native structure. After 100,000 Monte Carlo
      sweeps, the relative decrease in the mean rmsd, as one switches from thrashing to
      wriggling, rises from 11% for the protein 3LZM with 164 amino acids (aa) to 40%
      for the protein 1A1S with 313 aa and 47% for the protein 16PK with 415 aa. These
      results suggest that wriggling is useful and that its utility increases with the
      size of the protein. One may implement wriggling on a parallel computer or a
      computer farm.

PMID- 11964252
TI  - Nature of Interaction between basic fibroblast growth factor and the
      antiangiogenic drug 7,7-(carbonyl-bis[imino-N-methyl-4,2-pyrrolecarbonylimino[N
      methyl-4,2-pyrrole]-carbonylimino])-bis-(1,3-naphtalene disulfonate). II. Removal
      of polar interactions affects protein folding.
AB  - Fibroblast growth factor-2 (basic FGF), a potent inducer of angiogenesis, and the
      naphthalene sulfonic distamycin A derivative, 7,7-(carbonyl-bis[imino-N-methyl
      4,2-pyrrolecarbonylimino[N-methyl-4,2-pyrrole]-carbonylimino])-bis-(1,3
      naphtalene disulfonate) (PNU145156E), which exhibits in vivo antiangiogenic
      activity, form a tight reversible (1:1) complex. PNU145156E binds to the heparin
      and the selenate-binding sites on bFGF. The cis bFGF-heparin (2:1) complex,
      essential for the activation of the angiogenic process, is thus prevented. The
      nature of the forces involved in bFGF:PNU145156E complex, using the wild-type and
      the K128Q, K138Q, K134Q, and K128Q-K138Q point mutated bFGFs was sought. Based on
      thermodynamic analysis of the complexation constants, protein temperature
      stability profiles by ultraviolet absorption, circular dichroism measurements,
      fluorescence Forster energy-transfer, and anisotropy studies, in harmony with the
      published x-ray crystallographic structure, the following molecular interactions
      are proposed: reduced coulombic interactions, hence loosening of the complex by
      the removal of charged polar groups from the bFGF-heparin binding cleft resulted
      in decreased binding constants and in a change in the binding mode from polar to
      nonpolar. Concomitantly, upon mutation, the protein was rendered more compact,
      less flexible, and less aqueously exposed compared with the wild type. These were
      further pronounced with the double mutant: weaker dominantly nonpolar protein
      drug interactions were accompanied by conspicuous folding. With heparin, however,
      wild-type bFGF forms a tighter complex with a more compact structure.

PMID- 11964254
TI  - Properties of water molecules in the active site gorge of acetylcholinesterase
      from computer simulation.
AB  - A 10-ns trajectory from a molecular dynamics simulation is used to examine the
      structure and dynamics of water in the active site gorge of acetylcholinesterase
      to determine what influence water may have on its function. While the confining
      nature of the deep active site gorge slows down and structures water
      significantly compared to bulk water, water in the gorge is found to display a
      number of properties that may aid ligand entry and binding. These properties
      include fluctuations in the population of gorge waters, moderate disorder and
      mobility of water in the middle and entrance to the gorge, reduced water hydrogen
      bonding ability, and transient cavities in the gorge.

PMID- 11964256
TI  - Two-dimensional crystal structures of protein kinase C-delta, its regulatory
      domain, and the enzyme complexed with myelin basic protein.
AB  - Two-dimensional crystals of protein kinase C (PKC) delta, its regulatory domain
      (RDdelta), and the enzyme complexed with the substrate myelin basic protein have
      been grown on lipid monolayers composed of phosphatidylcholine:
      phosphatidylserine: diolein (45:50:5, molar ratio). Images have been
      reconstructed to 10-A resolution. The unit cells of all three proteins have cell
      edges a = b and interedge angle gamma = 60 degrees. RDdelta has an edge length of
      33 +/- 1 A, and its reconstruction is donut shaped. The three-dimensional
      reconstructions from the PKCdelta C1b crystal structure () can be accommodated in
      this two-dimensional projection. Intact PKCdelta has an edge length of 46 +/- 1 A
      in the presence or absence of a nonhydrolyzable ATP analog, AMP-PnP. Its
      reconstruction has a similar donut shape, which can accommodate the C1b domain,
      but the spacing between donuts is greater than that in RDdelta; some additional
      structure is visible between the donuts. The complex of PKCdelta and myelin basic
      protein, with or without AMP-PnP, has an edge length of 43 +/- 1 A and a distinct
      structure. These results indicate that the C1 domains of RDdelta are tightly
      packed in the plane of the membrane in the two-dimensional crystals, that there
      is a single molecule of PKCdelta in the unit cell, and that its interaction with
      myelin basic protein induces a shift in conformation and/or packing of the
      enzyme.

PMID- 11964255
TI  - Conformation of a trimannoside bound to mannose-binding protein by nuclear
      magnetic resonance and molecular dynamics simulations.
AB  - A model of the carbohydrate recognition domain of the serum form of mannose
      binding protein (MBP) from rat complexed with methyl 3,6-di-O-(alpha-D
      mannopyranosyl)-alpha-D-mannopyranoside is presented. Allowed conformations for
      the bound sugar were derived from simulated annealing protocols incorporating
      distance restraints computed from transferred NOESY spectra. The resulting sugar
      conformations were then modeled into the MBP binding site, and these models of
      the complex were refined using molecular dynamics (MD) simulations in the
      presence of solvent water. These studies indicate that only one of the two major
      conformations of the alpha(1-->6) linkage found in solution is significantly
      populated in the bound state (omega = 60 degrees ), whereas the alpha(1-->3)
      linkage samples at least two states, similar to its behavior in free solution.
      The bound conformation allows direct hydrogen bonds to form between the sugar and
      K182 of MBP, in addition to other water-mediated hydrogen bonds. Estimates of
      binding constants of candidate complexes based on changes in solvent-accessible
      surface areas upon binding support the NMR and MD results. These estimates
      further suggest that the enthalpic gains of the additional sugar-MBP interactions
      in a trisaccharide as opposed to a monosaccharide are offset by entropic
      penalties, offering an explanation for previous binding data.

PMID- 11964257
TI  - Conformational changes and orientation of Humicola lanuginosa lipase on a solid
      hydrophobic surface: an in situ interface Fourier transform infrared-attenuated
      total reflection study.
AB  - This study was done to better understand how lipases are activated at an
      interface. We investigated the conformational and solvation changes occurring
      during the adsorption of Humicola lanuginosa lipase (HLL) onto a hydrophobic
      surface using Fourier transform infrared-attenuated total reflection
      spectroscopy. The hydrophobic surfaces were obtained by coating silicon
      attenuated total reflection crystal with octadecyltrichlorosilane. Analysis of
      vibrational spectra was used to compare the conformation of HLL adsorbed at the
      aqueous-solid interface with its conformation in solution. X-ray crystallography
      has shown that HLL exists in two conformations, the closed and open forms. The
      conformational changes in HLL caused by adsorption onto the surface were compared
      with those occurring in three reference proteins, bovine serum albumin, lysozyme,
      and alpha-chymotrypsin. Adsorbed protein layers were prepared using proteins
      solutions of 0.005 to 0.5 mg/mL. The adsorptions of bovine serum albumin,
      lysozyme, and alpha-chymotrypsin to the hydrophobic support were accompanied by
      large unfoldings of ordered structures. In contrast, HLL underwent no secondary
      structure changes at first stage of adsorption, but there was a slight folding of
      beta-structures as the lipase monolayer became complete. Solvation studies using
      deuterated buffer showed an unusual hydrogen/deuterium exchange of the peptide
      CONH groups of the adsorbed HLL molecules. This exchange is consistent with the
      lipase being in the native open conformation at the water/hydrophobic interface.

PMID- 11964258
TI  - Comparison of helix interactions in membrane and soluble alpha-bundle proteins.
AB  - Helix-helix interactions are important for the folding, stability, and function
      of membrane proteins. Here, two independent and complementary methods are used to
      investigate the nature and distribution of amino acids that mediate helix-helix
      interactions in membrane and soluble alpha-bundle proteins. The first method
      characterizes the packing density of individual amino acids in helical proteins
      based on the van der Waals surface area occluded by surrounding atoms. We have
      recently used this method to show that transmembrane helices pack more tightly,
      on average, than helices in soluble proteins. These studies are extended here to
      characterize the packing of interfacial and noninterfacial amino acids and the
      packing of amino acids in the interfaces of helices that have either right- or
      left-handed crossing angles, and either parallel or antiparallel orientations. We
      show that the most abundant tightly packed interfacial residues in membrane
      proteins are Gly, Ala, and Ser, and that helices with left-handed crossing angles
      are more tightly packed on average than helices with right-handed crossing
      angles. The second method used to characterize helix-helix interactions involves
      the use of helix contact plots. We find that helices in membrane proteins exhibit
      a broader distribution of interhelical contacts than helices in soluble proteins.
      Both helical membrane and soluble proteins make use of a general motif for helix
      interactions that relies mainly on four residues (Leu, Ala, Ile, Val) to mediate
      helix interactions in a fashion characteristic of left-handed helical coiled
      coils. However, a second motif for mediating helix interactions is revealed by
      the high occurrence and high average packing values of small and polar residues
      (Ala, Gly, Ser, Thr) in the helix interfaces of membrane proteins. Finally, we
      show that there is a strong linear correlation between the occurrence of residues
      in helix-helix interfaces and their packing values, and discuss these results
      with respect to membrane protein structure prediction and membrane protein
      stability.

PMID- 11964259
TI  - GTP-induced membrane binding and ion channel activity of annexin VI: is annexin
      VI a GTP biosensor?
AB  - Annexin VI (AnxVI) formed ion channels in planar lipid bilayers that were induced
      by the addition of millimolar guanosine 5'-triphosphate (GTP) at pH 7.4 and that
      were not accompanied by a penetration of the protein into the membrane
      hydrophobic region. GTP-influenced interactions of AnxVI with Ca2+/liposomes
      produced small structural alterations as revealed by circular dichroism and
      infrared spectroscopies. Guanosine 5'-3-O-(thio)-triphosphate (GTPgammaS) binding
      to AnxVI, promoted by the photorelease of GTPgammaS from GTPgammaS[1-(4,5
      dimethoxy-2-nitrophenyl)-ethyl] (caged-GTPgammaS), affected three to four amino
      acid residues of AnxVI in the presence of Ca2+/liposomes, while about eight or
      nine amino acid residues were altered in their absence. This suggested that the
      nucleotide-binding site overlapped the lipid-binding domain of AnxVI. The binding
      of the fluorescent GTP analog, 2'-(or 3')-O-(2,4,6-trinitrophenyl)guanosine 5'
      triphosphate (TNP-GTP) to AnxVI was optimal in the presence of Ca2+/liposomes,
      with a dissociation constant (K(d)) of 1 microM and stoichiometry of 1. TNP-GTP
      promoted fluorescence resonance energy transfer from tryptophan residues to the
      nucleotide. Ion conductance and fluorescence measurements of the C- and N
      terminal fragments of AnxVI indicated distinct GTP-binding properties, suggesting
      that the existence of the GTP-induced ion channel activity of AnxVI is associated
      with the flexibility of the two halves of the protein. Such structural
      flexibility could contribute to a molecular mechanism of AnxVI acting as a GTP
      biosensor.

PMID- 11964260
TI  - Computational studies on prion proteins: effect of Ala(117)-->Val mutation.
AB  - Molecular dynamics calculations demonstrated the conformational change in the
      prion protein due to Ala(117)-->Val mutation, which is related to Gerstmann
      Straussler-Sheinker disease, one of the familial prion diseases. Three kinds of
      model structures of human and mouse prion proteins were examined: (model 1)
      nuclear magnetic resonance structures of human prion protein HuPrP (125-228) and
      mouse prion protein MoPrP (124-224), each having a globular domain consisting of
      three alpha-helices and an antiparallel beta-sheet; (model 2) extra peptides
      including Ala(117) (109-124 in HuPrP and 109-123 in MoPrP) plus the nuclear
      magnetic resonance structures of model 1; and (model 3) extra peptides including
      Val(117) (109-124 in HuPrP and 109-123 in MoPrP) plus the nuclear magnetic
      resonance structures of model 1. The results of molecular dynamics calculations
      indicated that the globular domains of models 1 and 2 were stable and that the
      extra peptide in model 2 tended to form a new alpha-helix. On the other hand, the
      globular domain of model 3 was unstable, and the beta-sheet region increased
      especially in HuPrP.

PMID- 11964261
TI  - Role of the coordinating histidine in altering the mixed valency of Cu(A): an
      electron nuclear double resonance-electron paramagnetic resonance investigation.
AB  - The binuclear Cu(A) site engineered into Pseudomonas aeruginosa azurin has
      provided a Cu(A)-azurin with a well-defined crystal structure and a CuSSCu core
      having two equatorial histidine ligands, His120 and His46. The mutations
      His120Asn and His120Gly were made at the equatorial His120 ligand to understand
      the histidine-related modulation to Cu(A), notably to the valence delocalization
      over the CuSSCu core. For these His120 mutants Q-band electron nuclear double
      resonance (ENDOR) and multifrequency electron paramagnetic resonance (EPR) (X, C,
      and S-band), all carried out under comparable cryogenic conditions, have provided
      markedly different electronic measures of the mutation-induced change. Q-band
      ENDOR of cysteine C(beta) protons, of weakly dipolar-coupled protons, and of the
      remaining His46 nitrogen ligand provided hyperfine couplings that were like those
      of other binuclear mixed-valence Cu(A) systems and were essentially unperturbed
      by the mutation at His120. The ENDOR findings imply that the Cu(A) core
      electronic structure remains unchanged by the His120 mutation. On the other hand,
      multifrequency EPR indicated that the H120N and H120G mutations had changed the
      EPR hyperfine signature from a 7-line to a 4-line pattern, consistent with
      trapped-valence, Type 1 mononuclear copper. The multifrequency EPR data imply
      that the electron spin had become localized on one copper by the His120 mutation.
      To reconcile the EPR and ENDOR findings for the His120 mutants requires that
      either: if valence localization to one copper has occurred, the spin density on
      the cysteine sulfurs and the remaining histidine (His46) must remain as it was
      for a delocalized binuclear Cu(A) center, or if valence delocalization persists,
      the hyperfine coupling for one copper must markedly diminish while the overall
      spin distribution on the CuSSCu core is preserved.

PMID- 11964263
TI  - Precise nanometer localization analysis for individual fluorescent probes.
AB  - Calculation of the centroid of the images of individual fluorescent particles and
      molecules allows localization and tracking in light microscopes to a precision
      about an order of magnitude greater than the microscope resolution. The factors
      that limit the precision of these techniques are examined and a simple equation
      derived that describes the precision of localization over a wide range of
      conditions. In addition, a localization algorithm motivated from least-squares
      fitting theory is constructed and tested both on image stacks of 30-nm
      fluorescent beads and on computer-generated images (Monte Carlo simulations).
      Results from the algorithm show good agreement with the derived precision
      equation for both the simulations and actual images. The availability of a simple
      equation to describe localization precision helps investigators both in assessing
      the quality of an experimental apparatus and in directing attention to the
      factors that limit further improvement. The precision of localization scales as
      the inverse square root of the number of photons in the spot for the shot noise
      limited case and as the inverse of the number of photons for the background noise
      limited case. The optimal image magnification depends on the expected number of
      photons and background noise, but, for most cases of interest, the pixel size
      should be about equal to the standard deviation of the point spread function.

PMID- 11964262
TI  - Single molecule recognition of protein binding epitopes in brush border membranes
      by force microscopy.
AB  - Sidedness and accessibility of protein epitopes in intact brush border membrane
      vesicles were analyzed by detecting single molecule interaction forces using
      molecular recognition force microscopy in aqueous physiological solutions.
      Frequent antibody-antigen recognition events were observed with a force
      microscopy tip carrying an antibody directed against the periplasmically located
      gamma-glutamyltrans- peptidase, suggesting a right side out orientation of the
      vesicles. Phlorizin attached to the tips bound to NA+/D-glucose cotransporter
      molecules present in the vesicles. The recognition was sodium dependent and
      inhibited by free phlorizin and D-glucose, and revealed an apparent K(D) of 0.2
      microM. Binding events were also observed with an antibody directed against the
      epitope aa603-aa630 close to the C terminus of the transporter. In the presence
      of phlorizin the probability of antibody binding was reduced but the most
      probable unbinding force f(u) = 100 pN remained unchanged. In the presence of D
      glucose and sodium, however, both the binding probability and the most probable
      binding force (f(u) = 50 pN) were lower than in its absence. These studies
      demonstrate that molecular recognition force microscopy is a versatile tool to
      probe orientation and conformational changes of epitopes of membrane components
      during binding and trans-membrane transport.

PMID- 11964264
TI  - Quantitative comparison of zero-loss and conventional electron diffraction from
      two-dimensional and thin three-dimensional protein crystals.
AB  - The scattering cross-section of atoms in biological macromolecules for both
      elastically and inelastically scattered electrons is approximately 100,000 times
      larger than that for x-ray. Therefore, much smaller (<1 microm) and thinner
      (<0.01 microm) protein crystals than those used for x-ray crystallography can be
      used to analyze the molecular structures by electron crystallography. But,
      inelastic scattering is a serious problem. We examined electron diffraction data
      from thin three-dimensional (3-D) crystals (600-750 A thick) and two-dimensional
      (2-D) crystals (approximately 60 A thick), both at 93 K, with an energy filtering
      electron microscope operated at an accelerating voltage of 200 kV. Removal of
      inelastically scattered electrons significantly improved intensity data
      statistics and R(Friedel) factor in every resolution range up to 3-A resolution.
      The effect of energy filtering was more prominent for thicker crystals but was
      significant even for thin crystals. These filtered data sets showed better
      intensity statistics even in comparison with data sets collected at 4 K and an
      accelerating voltage of 300 kV without energy filtering. Thus, the energy filter
      will be an effective and important tool in the structure analysis of thin 3-D and
      2-D crystals, particularly when data are collected at high tilt angle.

PMID- 11964265
TI  - Determination of elastic moduli of thin layers of soft material using the atomic
      force microscope.
AB  - We address three problems that limit the use of the atomic force microscope when
      measuring elastic moduli of soft materials at microscopic scales. The first
      concerns the use of sharp cantilever tips, which typically induce local strains
      that far exceed the linear material regime. We show that this problem can be
      alleviated by using microspheres as probes, and we establish the criteria for
      their use. The second relates to the common use of the Hertz contact mechanics
      model, which leads to significant errors when applied to thin samples. We develop
      novel, simple to use corrections to apply for such cases. Samples that are either
      bonded or not bonded to a rigid substrate are considered. The third problem
      concerns the difficulty in establishing when contact occurs on a soft material.
      We obtain error estimates for the elastic modulus resulting from such uncertainty
      and discuss the sensitivity of the estimation methods to error in contact point.
      The theoretical and experimental results are compared to macroscopic measurements
      on poly(vinyl-alcohol) gels.

PMID- 11964270
TI  - Differentiation plasticity of hematopoietic cells.

PMID- 11964269
TI  - Prevention of graft-versus-host disease while preserving graft-versus-leukemia
      effect after selective depletion of host-reactive T cells by photodynamic cell
      purging process.
AB  - In this study, we investigated the possibility of selective depletion of donor
      alloantigen-specific T cells from C57BL/6 (H-2(b)) mice to prevent graft-versus
      host disease (GVHD). These cells were first activated with irradiated BALB/c (H
      2(d)) host spleen cells in a 5-day mixed lymphocyte culture. Following this
      activation, a photoactive rhodamine derivative called 4,5-dibromorhodamine 123
      (TH9402), was added. This compound is selectively retained in the mitochondria of
      activated host-reactive cells but not tumor- or third-party-specific resting
      cells. The treated cells were subsequently exposed to visible light (514 nm) to
      deplete the TH9402-enriched activated host-reactive cells. Treatment with
      photodynamic cell purging process (PDP) inhibited antihost responses measured by
      cytotoxic T lymphocytes (CTL) by 93%, and interferon-gamma production by 66%. By
      contrast, anti-BCL1 (BALB/c-origin leukemia/lymphoma) and anti-third-party
      C3H/HeJ (H-2(k)) responses were preserved. PDP-treated primed C57BL/6 cells were
      further tested in vivo. All lethally irradiated BALB/c mice inoculated with BCL1
      cells and T-cell-depleted bone marrow cells developed leukemia by day +30, with
      50% mortality by 100 days. All mice died of GVHD after addition of 5 x 10(6)
      untreated primed C57BL/6 cells. However, addition of same numbers of PDP-treated
      cells allowed 90% of the recipients to survive more than 100 days without
      detectable BCL1 tumor cells and free of GVHD. Moreover, PDP-treated primed
      C57BL/6 cells retained the ability to induce GVHD in the third-party C3H/HeJ
      mice. These data suggest that PDP can selectively deplete host alloantigen
      specific T cells for GVHD prevention and immune and antileukemia function
      preserve.

PMID- 11964266
TI  - Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein.
AB  - Two-photon (2P) ratiometric redox fluorometry and microscopy of pyridine
      nucleotide (NAD(P)H) and flavoprotein (FP) fluorescence, at 800-nm excitation,
      has been demonstrated as a function of mitochondrial metabolic states in isolated
      adult dog cardiomyocytes. We have measured the 2P-excitation spectra of NAD(P)H,
      flavin adenine dinucleotide (FAD), and lipoamide dehydrogenase (LipDH) over the
      wavelength range of 720-1000 nm. The 2P-excitation action cross sections
      (sigma2P) increase rapidly at wavelengths below 800 nm, and the maximum sigma2P
      of LipDH is approximately 5 and 12 times larger than those of FAD and NAD(P)H,
      respectively. Only FAD and LipDH can be efficiently excited at wavelengths above
      800 nm with a broad 2P-excitation band around 900 nm. Two autofluorescence
      spectral regions (i.e., approximately 410-490 nm and approximately 510-650 nm) of
      isolated cardiomyocytes were imaged using 2P-laser scanning microscopy. At 750-nm
      excitation, fluorescence of both regions is dominated by NAD(P)H emission, as
      indicated by fluorescence intensity changes induced by mitochondrial inhibitor
      NaCN and mitochondria uncoupler carbonyl cyanide p-(trifluoromethoxy) phenyl
      hydrazone (FCCP). In contrast, 2P-FP fluorescence dominates at 900-nm excitation,
      which is in agreement with the sigma2P measurements. Finally, 2P-autofluorescence
      emission spectra of single cardiac cells have been obtained, with results
      suggesting potential for substantial improvement of the proposed 2P-ratiometric
      technique.

PMID- 11964271
TI  - How we diagnose and treat deep vein thrombosis.
AB  - Making a diagnosis of deep vein thrombosis (DVT) requires both clinical
      assessment and objective testing because the clinical features are nonspecific
      and investigations can be either falsely positive or negative. The initial step
      in the diagnostic process is to stratify patients into high-, intermediate-, or
      low-risk categories using a validated clinical model. When the clinical
      probability is intermediate or high and the venous ultrasound result is positive,
      acute symptomatic DVT is confirmed. Similarly, when the probability is low and
      the ultrasound result is normal, DVT is ruled out. A low clinical probability
      combined with a negative D-dimer result can also be used to rule out DVT, thereby
      obviating the need for ultrasonography. In contrast, when the clinical assessment
      is discordant with the results of objective testing, serial venous
      ultrasonography or venography is required to confirm or refute a diagnosis of
      DVT. Once a patient is diagnosed with an acute DVT, low-molecular-weight heparin
      (LMWH) is the agent of choice for initial therapy and oral anticoagulant therapy
      is the standard for long-term secondary prophylaxis. Therapy should continue for
      at least 3 months; the decision to continue treatment beyond 3 months is made by
      weighing the risks of recurrent thrombosis and anticoagulant-related bleeding,
      and is influenced by patient preference. Screening for associated thrombophilia
      is not indicated routinely, but should be performed in selected patients whose
      clinical features suggest an underlying hypercoagulable state. Several new
      anticoagulants with theoretical advantages over existing agents are undergoing
      evaluation in phase 3 studies in patients with venous thromboembolism.

PMID- 11964272
TI  - Signaling through ZAP-70 is required for CXCL12-mediated T-cell transendothelial
      migration.
AB  - Transendothelial migration of activated lymphocytes from the blood into the
      tissues is an essential step for immune functions. The housekeeping chemokine
      CXCL12 (or stroma cell-derived factor-1alpha), a highly efficient chemoattractant
      for T lymphocytes, drives lymphocytes to sites where they are highly likely to
      encounter antigens. This suggests that cross-talk between the T-cell receptor
      (TCR) and CXCR4 (the CXCL12 receptor) might occur within these sites. Here we
      show that the zeta-associated protein 70 (ZAP-70), a key element in TCR
      signaling, is required for CXCR4 signal transduction. The pharmacologic
      inhibition of ZAP-70, or the absence of ZAP-70 in Jurkat T cells and in primary
      CD4(+) T cells obtained from a patient with ZAP deficiency, resulted in an
      impairment of transendothelial migration that was rescued by the transfection of
      ZAP-70. Moreover, the overexpression of mutated forms of ZAP-70, whose kinase
      domain was inactivated, also abrogated the migratory response of Jurkat T cells
      to CXCL12. In contrast, no involvement of ZAP-70 in T-cell arrest on inflammatory
      endothelium under flow conditions or in CXCL12-induced actin polymerization was
      observed. Furthermore, CXCL12 induced time-dependent phosphorylation of ZAP-70,
      Vav1, and extracellular signal-regulated kinases (ERKs); the latter were reduced
      in the absence of functional ZAP-70. However, though a dominant-negative Vav1
      mutant (Vav1 L213A) blocked CXCL12-induced T-cell migration, pharmacologic
      inhibition of the ERK pathway did not affect migration, suggesting that ERK
      activation is dispensable for T-cell chemotaxis. We conclude that cross-talk
      between the ZAP-70 signaling pathway and the chemokine receptor CXCR4 is required
      for T-cell migration.

PMID- 11964274
TI  - Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic
      anemia.
AB  - A serious complication of aplastic anemia (AA) is its evolution to clonal
      hematologic diseases such as myelodysplasia (MDS) and leukemia, which is usually
      associated with the appearance of a cytogenetic abnormality in bone marrow cells.
      We present here an analysis of a cohort of 30 patients with otherwise typical AA
      in whom clonal karyotypic evolution was observed during frequent periodic marrow
      examinations. The actuarial risk for this complication has been estimated in
      other studies at around 15% at 5 years. Conversion from normal to abnormal
      karyotype occurred at a constant rate after initial diagnosis, with about 50% of
      cases developing within the first 30 months. Transient chromosomal abnormalities
      were infrequent. Clinically, AA patients with clonal cytogenetic patterns were
      heterogenous; a variety of karyotypic defects with numerical and structural
      abnormalities of chromosome 7 accounted for 40% of all cases followed by trisomy
      8, structural and numerical abnormalities of chromosome 13, deletion of Y
      chromosome, and complex cytogenetic abnormalities. Unlike in primary MDS,
      aberrancies of chromosome 5 and 20 were infrequent. The clinical course depended
      on the specific abnormal cytogenetic pattern. Most deaths related to leukemic
      transformation occurred in patients with abnormalities of chromosome 7 or complex
      cytogenetic alterations or both. Evolution of chromosome 7 abnormalities was seen
      most often in refractory patients who had failed to respond to therapy. In
      contrast, trisomy 8 developed in patients with good hematologic responses who
      often required chronic immunosuppression with cyclosporine A (CsA), and survival
      was excellent. Although AA patients with monosomy 7 showed a similar prognosis to
      those with primary MDS, trisomy 8 in AA appears to have a more favorable
      prognosis than in MDS.

PMID- 11964273
TI  - Increased expression of the inflammatory chemokine CXC chemokine ligand
      9/monokine induced by interferon-gamma in lymphoid tissues of rhesus macaques
      during simian immunodeficiency virus infection and acquired immunodeficiency
      syndrome.
AB  - Chemokines are important mediators of cell trafficking during immune inductive
      and effector activities, and dysregulation of their expression might contribute
      to the pathogenesis of human immunodeficiency virus type 1 and the related simian
      immunodeficiency virus (SIV). To understand better the effects of SIV infection
      on lymphoid tissues in rhesus macaques, we examined chemokine messenger RNA
      (mRNA) expression patterns by using DNA filter array hybridization. Of the 34
      chemokines examined, the interferon gamma (IFN-gamma)-inducible chemokine CXC
      chemokine ligand 9/monokine induced by interferon-gamma (CXCL9/Mig) was one of
      the most highly up-regulated chemokines in rhesus macaque spleen tissue early
      after infection with pathogenic SIV. The relative levels of expression of
      CXCL9/Mig mRNA in spleen and lymph nodes were significantly increased after
      infection with SIV in both quantitative image capture and analysis and real-time
      reverse transcriptase-polymerase chain reaction assays. In addition, in situ
      hybridization for CXCL9/Mig mRNA revealed that the patterns of expression were
      altered after SIV infection. Associated with the increased expression of
      CXCL9/Mig were increased numbers of IFN-gamma mRNA-positive cells in tissues and
      reduced percentages of CXC chemokine receptor (CXCR) 3(+)/CD3(+) and
      CXCR3(+)/CD8(+) lymphocytes in peripheral blood. We propose that SIV replication
      in vivo initiates IFN-gamma-driven positive-feedback loops in lymphoid tissues
      that disrupt the trafficking of effector T lymphocytes and lead to chronic local
      inflammation, thereby contributing to immunopathogenesis.

PMID- 11964275
TI  - Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a
      pilot report.
AB  - In the past 6 years, we treated 129 patients who had acute promyelocytic leukemia
      (APL) with a new arsenic agent, oral tetra-arsenic tetra-sulfide (As(4)S(4)).
      Nineteen of the patients had newly diagnosed APL, 7 had first relapse, and 103
      had hematologic complete remission (HCR). HCR was achieved in all patients with
      newly diagnosed APL and in all those with hematologic relapse. Of 16 patients
      with newly diagnosed disease and available cytogenetic and molecular analyses, 14
      had cytogenetic and molecular complete remission (CR). Cytogenetic and molecular
      CR was also obtained in 5 of the 7 patients with hematologic relapse. In the HCR
      group, 35 of 44 patients positive for PML-RARalpha at baseline became negative.
      In the newly diagnosed group, estimated disease-free survival (DFS) rates for 1
      and 3 years were 86.1% and 76.6%, respectively, with a median follow-up time of
      13.5 months (range, 2-40 months). In the HCR group, DFS rates for 1 and 6 years
      were 96.7% and 87.4%, respectively, with a median follow-up of 23 months (range,
      2-71 months). Treatment with As(4)S(4) was well tolerated, with only moderate
      side effects, including asymptomatic prolongation of corrected QT interval,
      transient elevation in liver enzyme levels, rash, and mild gastrointestinal
      discomfort; neither myelosuppression nor appreciable long-term side effects
      occurred. Degeneration or apoptosis of APL promyelocytes was observed during
      As(4)S(4) therapy. Pharmacokinetic studies showed that the agent was absorbed
      rapidly. Most urinary arsenic excretion occurred within the first 24 hours. Both
      blood and urinary arsenic levels declined after discontinuation of As(4)S(4). Our
      results show, for the first time, that As(4)S(4) treatment alone is highly
      effective and safe in both remission induction and maintenance therapy in
      patients with APL, regardless of disease stage.

PMID- 11964276
TI  - Moyamoya syndrome in childhood sickle cell disease: a predictive factor for
      recurrent cerebrovascular events.
AB  - We conducted a retrospective study to determine whether the presence of moyamoya
      collaterals influenced the risk of recurrence of cerebrovascular events (CVEs:
      stroke or transient ischemic attack) in patients with sickle cell disease placed
      on chronic transfusions after a stroke. Forty-three patients with homozygous
      sickle cell anemia (HbSS) and 1 with HbSO(Arab) (16 females, 28 males) who had
      suffered strokes while under the age of 18 were studied. All patients had been on
      transfusions aimed at maintaining the sickle hemoglobin (HbS) level below 30%.
      They were followed for a mean of 6.6 years (2.2 to 20.4 years). The presence of
      collaterals was diagnosed based on either magnetic resonance angiography or
      conventional angiography. Eighteen (41%) of the 44 patients suffered recurrent
      CVEs. Nineteen (43%) (6 females, 13 males) patients had moyamoya collaterals.
      Eleven (58%) of these 19 experienced 21 total recurrent CVEs, including 4 strokes
      in 4 patients (21%). In comparison, 7 (28%) of 25 patients without moyamoya
      collaterals experienced 9 recurrent CVEs (P <.05) with only 1 recurrent stroke
      (4%). Moyamoya patients were also more likely to have 2 recurrent CVEs (42% vs
      8%, P <.05) as well as poorer neuropsychological testing results. A proportional
      hazards regression analysis indicated that patients with moyamoya were more than
      twice as likely to incur a subsequent CVE (hazard ratio, 2.40; 95% confidence
      interval, 0.85, 6.75). We conclude that up to 41% of patients with sickle cell
      disease experience recurrent CVEs after an initial stroke despite chronic
      transfusions and that the risk of recurrence is significantly higher for those
      who have moyamoya collaterals.

PMID- 11964277
TI  - Unrelated marrow transplantation for children with acute lymphoblastic leukemia
      in second remission.
AB  - Allogeneic bone marrow transplantation (BMT) may be curative for more patients
      than chemotherapy for the child with relapsed acute lymphoblastic leukemia. This
      study reviewed the outcomes of 363 children with acute lymphoblastic leukemia in
      second remission who received unrelated donor BMT from 1988 to 2000 in order to
      define prognostic factors that affect leukemia-free survival (LFS). Median
      patient age was 9 years (range, 0-19 years), and median follow-up 29 was months
      (range, 0-125 months). The median duration of first remission was 24 months
      (range, 0-109 months). Prognostic factors, including age, duration of first
      remission, HLA matching, and graft-versus-host (GVH) disease, were analyzed using
      both univariate and multivariate analyses. Overall survival was 38%, and LFS was
      36% at 5 years. LFS was significantly worse for patients 15 years or older (log
      rank, P =.009). HLA matching was associated with improved LFS. Acute GVH disease
      developed in 71%, with 29% having grades III-IV. The incidence of chronic GVH
      disease was 39% for patients who survived more than 80 days and was significantly
      higher for female patients receiving marrow from female donors (P =.0009).
      Transplantation-related mortality was 42% and was associated with HLA mismatches,
      age 15 years and older, and first remission less than 12 months. The 5-year
      estimate for relapse was 22%, with first remission at least 6 months associated
      with a lower risk. Results of unrelated donor BMT appear similar to multi
      institutional studies of matched related donor BMT, and this approach appears to
      be curative for many patients. However, innovative approaches are needed for
      patients with initial remissions of less than 6 months and for older teenagers.

PMID- 11964278
TI  - High-dose chemo-radioimmunotherapy with autologous stem cell support for relapsed
      mantle cell lymphoma.
AB  - Relapsed mantle cell lymphoma is a radiation-sensitive malignancy that is
      unlikely to be cured by treatment with conventional high-dose therapy and
      autologous stem cell transplantation. We tested the safety and efficacy of using
      a CD20-specific monoclonal antibody conjugated with (131)I to deliver high-dose
      radiation selectively to all lymphoma sites. Patients with relapsed or refractory
      mantle cell lymphoma received infusions of (131)I-labeled CD20-specific
      monoclonal antibody (Tositumomab). The antibody dose was 1.7 mg/kg body weight,
      and the amount of (131)I was calibrated to deliver 20 to 25 Gy to vital normal
      organs. This treatment was followed 10 days later by administration of high-dose
      etoposide (30-60 mg/kg), cyclophosphamide (60-100 mg/kg), and infusion of
      cryopreserved autologous stem cells. The 16 patients in this study had received a
      median of 3 prior treatments, and 7 had chemotherapy-resistant disease. The
      median dose of (131)I was 510 mCi (18.87 GBq). There were no therapy-related
      deaths. Among the 11 patients with conventionally measurable disease at the time
      of treatment, the respective complete and overall response rates were 91% and
      100%. Fifteen patients remain alive, and 12 have had no progression of lymphoma
      at 6 to 57 months from transplantation and 16 to 97 months from diagnosis.
      Overall survival at 3 years from transplantation is estimated at 93%, and
      progression-free survival is estimated at 61%. High-dose treatment with (131)I
      Tositumomab, etoposide, and cyclophosphamide results in a high remission rate and
      may provide long-term disease-free survival for patients with relapsed or
      refractory mantle cell lymphoma.

PMID- 11964279
TI  - Maintenance therapy with alternate-day prednisone improves survival in multiple
      myeloma patients.
AB  - The role of maintenance therapy in multiple myeloma is controversial. Recent
      studies have shown an improvement in both progression-free and overall survival
      for patients receiving maintenance treatment with a combination of interferon and
      glucocorticoids, compared with interferon alone. The role of glucocorticoids
      alone as maintenance therapy has not been previously addressed. We compared
      alternate-day, oral prednisone at 2 different dose levels (10 mg versus 50 mg)
      for remission maintenance among previously untreated myeloma patients following a
      response to induction with standard-dose vincristine, doxorubicin, and
      dexamethasone with prednisone (VAD-P) or VAD-P plus quinine (VAD-P/Q). There were
      250 eligible patients registered on Southwest Oncology Group study 9210 and
      randomized to receive VAD-P or VAD-P/Q. There were 125 patients achieving at
      least a 25% tumor reduction following induction therapy who were randomized to
      either physiologic (10 mg) or pharmacologic (50 mg) doses of alternate-day, oral
      prednisone until disease progression. At the time of study entry, patient
      characteristics were similar in VAD-P and VAD-P/Q patients and in the 2 arms
      randomized to maintenance therapy. After a median follow-up of 53 months, there
      was no difference in either progression-free or overall survival between the 2
      induction regimens. However, from the time of maintenance randomization, both
      progression-free (14 versus 5 months; P =.003) and overall survival (37 versus 26
      months; P =.05) were significantly improved in patients receiving 50 mg as
      compared with 10 mg alternate-day prednisone. There was no difference in
      treatment-related adverse events between the groups. Thus, 50 mg, oral, alternate
      day prednisone is effective maintenance treatment for multiple myeloma patients
      who achieve a response to induction chemotherapy. (Blood. 2002;99:3163-3168)

PMID- 11964280
TI  - Functional amelioration of murine galactosialidosis by genetically modified bone
      marrow hematopoietic progenitor cells.
AB  - Protective protein/cathepsin A (PPCA), a lysosomal carboxypeptidase, is deficient
      in the neurodegenerative lysosomal disorder galactosialidosis (GS). PPCA(-/-)
      mice display a disease course similar to that of severe human GS, resulting in
      nephropathy, ataxia, and premature death. Bone marrow transplantation (BMT) in
      mutant animals using transgenic BM overexpressing the corrective enzyme in either
      erythroid cells or monocytes/macrophages has proven effective for the improvement
      of the phenotype, and encouraged the use of genetically modified BM cells for ex
      vivo gene therapy of GS. Here, we established stable donor hematopoiesis in PPCA(
      /-) mice that received hematopoietic progenitors transduced with a murine stem
      cell virus (MSCV)-based, bicistronic retroviral vector overexpressing PPCA and
      the green fluorescent protein (GFP) marker. We observed complete correction of
      the disease phenotype in the systemic organs up to 10 months after
      transplantation. PPCA(+) BM-derived cells were detected in all tissues, with the
      highest expression in liver, spleen, BM, thymus, and lung. In addition, a
      lysosomal immunostaining was seen in nonhematopoietic cells, indicating efficient
      uptake of the corrective protein by these cells and cross-correction. Expression
      in the brain occurred throughout the parenchyma but was mainly localized on
      perivascular areas. However, PPCA expression in the central nervous system was
      apparently sufficient to delay the onset of Purkinje cell degeneration and to
      correct the ataxia. The long-term expression and internalization of the PPCA by
      cells of systemic organs and the clear improvement of the neurologic phenotype
      support the use of this approach for the treatment of GS in humans. (Blood.
      2002;99:3169-3178)

PMID- 11964281
TI  - Adapting a transforming growth factor beta-related tumor protection strategy to
      enhance antitumor immunity.
AB  - Transforming growth factor beta (TGF-beta), a pleiotropic cytokine that regulates
      cell growth and differentiation, is secreted by many human tumors and markedly
      inhibits tumor-specific cellular immunity. Tumors can avoid the differentiating
      and apoptotic effects of TGF-beta by expressing a nonfunctional TGF-beta
      receptor. We have determined whether this immune evasion strategy can be
      manipulated to shield tumor-specific cytotoxic T lymphocytes (CTLs) from the
      inhibitory effects of tumor-derived TGF-beta. As our model we used Epstein-Barr
      virus (EBV)-specific CTLs that are infused as treatment for EBV-positive Hodgkin
      disease but that are vulnerable to the TGF-beta produced by this tumor. CTLs were
      transduced with a retrovirus vector expressing the dominant-negative TGF-beta
      type II receptor HATGF-betaRII-Deltacyt. HATGF-betaRII-Deltacyt- but not green
      fluorescence protein (eGFP)-transduced CTLs was resistant to the
      antiproliferative and anticytotoxic effects of exogenous TGF-beta. Additionally,
      receptor-transduced cells continued to secrete cytokines in response to antigenic
      stimulation. TGF-beta receptor ligation results in phosphorylation of Smad2, and
      this pathway was disrupted in HATGF-betaRII-Deltacyt-transduced CTLs, confirming
      blockade of the signal transduction pathway. Long-term expression of TGF-betaRII
      Deltacyt did not affect CTL function, phenotype, or growth characteristics. Tumor
      specific CTLs expressing HATGF-betaRII-Deltacyt should have a selective
      functional and survival advantage over unmodified CTLs in the presence of TGF
      beta-secreting tumors and may be of value in treatment of these diseases.

PMID- 11964282
TI  - Role of protein kinase C in the phosphorylation of CD33 (Siglec-3) and its effect
      on lectin activity.
AB  - CD33 (Siglec-3) is a marker of myeloid progenitor cells, mature myeloid cells,
      and most myeloid leukemias. Although its biologic role remains unknown, it has
      been demonstrated to function as a sialic acid-specific lectin and a cell
      adhesion molecule. Many of the Siglecs (including CD33) have been reported to be
      tyrosine phosphorylated in the cytosolic tails under specific stimulation
      conditions. Here we report that CD33 is also a serine/threonine phosphoprotein,
      containing at least 2 sites of serine phosphorylation in its cytoplasmic domain,
      catalyzed by protein kinase C (PKC). Phosphorylation could be augmented by
      exposure to the protein kinase-activating cytokines interleukin 3,
      erythropoietin, or granulocyte-macrophage colony-stimulating factor, in a
      cytokine-dependent cell line, TF-1. The CD33 cytoplasmic tail was phosphorylated
      by PKC in vitro, in a Ca(++)/lipid-dependent manner. CHOK1 cells stably
      expressing CD33 with cytoplasmic tails of various length also showed phorbol
      myristate acetate (PMA)-dependent phosphorylation of CD33. Inhibition of CD33
      phosphorylation with pharmacologic agents resulted in an increase of sialic acid
      dependent rosette formation. Furthermore, the occupancy of the lectin site
      affected its basal level of phosphorylation. Rosette formation by COS cells
      expressing a form of CD33 lacking its cytoplasmic domain was not affected by
      these same agents. These data indicate that CD33 is a phosphoprotein, that its
      phosphorylation may be controlled by PKC downstream of cytokine stimulation, and
      that its phosphorylation is cross-regulated with its lectin activity. Notably,
      although this is the first example of serine/threonine phosphorylation in the
      subfamily of CD33-like Siglecs, some of the other members also have putative
      target sites in their cytoplasmic tails.

PMID- 11964283
TI  - Modulation of p210(BCR-ABL) activity in transduced primary human hematopoietic
      cells controls lineage programming.
AB  - Retroviral transduction of primary hematopoietic cells with human oncogenes
      provides a powerful approach to investigating the molecular mechanisms
      controlling the normal proliferation and differentiation of these cells. Here we
      show that primitive human CD34(+) cord blood cells, including multipotent as well
      as granulopoietic- and erythroid-restricted progenitors, can be efficiently
      transduced with a MSCV-BCR-ABL-IRES-GFP retrovirus, resulting in the sustained
      expression by their progeny of very high levels of tyrosine phosphorylated
      p210(BCR-ABL). Interestingly, even in the presence of growth factors that
      supported the exclusive production of granulopoietic cells from green fluorescent
      protein (GFP)-transduced control cells, BCR-ABL-transduced progenitor
      subpopulations generated large numbers of erythropoietin-independent terminally
      differentiating erythroid cells and reduced numbers of granulopoietic cells.
      Analyses of individual clones generated by single transduced cells in both
      semisolid and liquid cultures showed this BCR-ABL-induced erythroid
      differentiation response to be elicited at a high frequency from all types of
      transduced CD34(+) cells independent of their apparent prior lineage commitment
      status. Additional experiments showed that this erythroid differentiation
      response was largely prevented when the cells were transduced and maintained in
      the presence of the BCR-ABL-specific tyrosine kinase inhibitor, STI-571. These
      findings indicate that overexpression of BCR-ABL in primary human hematopoietic
      cells can activate an erythroid differentiation program in apparently
      granulopoietic-restricted cells through a BCR-ABL kinase-dependent mechanism,
      thus providing a new molecular tool for elucidating mechanisms underlying lineage
      fate determination in human hematopoietic cells and infidelity in human leukemia.

PMID- 11964284
TI  - Vitamin C inhibits granulocyte macrophage-colony-stimulating factor-induced
      signaling pathways.
AB  - Vitamin C is present in the cytosol as ascorbic acid, functioning primarily as a
      cofactor for enzymatic reactions and as an antioxidant to scavenge free radicals.
      Human granulocyte macrophage-colony-stimulating factor (GM-CSF) induces an
      increase in reactive oxygen species (ROS) and uses ROS for some signaling
      functions. We therefore investigated the effect of vitamin C on GM-CSF-mediated
      responses. Loading U937 cells with vitamin C decreased intracellular levels of
      ROS and inhibited the production of ROS induced by GM-CSF. Vitamin C suppressed
      GM-CSF-dependent phosphorylation of the signal transducer and activator of
      transcription 5 (Stat-5) and mitogen-activated protein (MAP) kinase (Erk1 and
      Erk2) in a dose-dependent manner as was phosphorylation of MAP kinase induced by
      both interleukin 3 (IL-3) and GM-CSF in HL-60 cells. In 293T cells transfected
      with alpha and beta GM-CSF receptor subunits (alphaGMR and betaGMR), GM-CSF
      induced phosphorylation of betaGMR and Jak-2 activation was suppressed by vitamin
      C loading. GM-CSF-mediated transcriptional activation of a luciferase reporter
      construct containing STAT-binding sites was also inhibited by vitamin C. These
      results substantiate the importance of ROS in GM-CSF signaling and indicate a
      role for vitamin C in downmodulating GM-CSF signaling responses. Our findings
      point to vitamin C as a regulator of cytokine redox-signal transduction in host
      defense cells and a possible role in controlling inflammatory responses.

PMID- 11964285
TI  - Accumulation of c-Cbl and rapid termination of colony-stimulating factor 1
      receptor signaling in interferon consensus sequence binding protein-deficient
      bone marrow-derived macrophages.
AB  - Mice deficient for the transcription factor interferon consensus sequence binding
      protein (ICSBP) are immunodeficient and develop granulocytic leukemia. Further
      analyses indicated that ICSBP is a molecular switch factor directing the
      differentiation of bipotential myeloid precursors to the monocytic lineage. To
      reveal the molecular mechanisms responsible for the deregulation of myelopoiesis,
      we examined the signaling of the colony-stimulating factor 1 receptor (CSF-1R) in
      bone marrow-derived macrophages (BMMs) from ICSBP(-/-) mice. We found that in the
      absence of ICSBP, CSF-1R signaling is attenuated as seen from an accelerated
      termination of Erk phosphorylation and reduced cell growth. This finding
      coincides with an increased CSF-1R ubiquitination and an enhanced accumulation of
      c-Cbl. c-Cbl is an ubiquitin-ligase known to down-regulate activated CSF-1R by
      targeting it to the endocytic pathway. Our results indicate that upon CSF-1R
      activation, c-Cbl itself is partly proteolytically degraded in ICSBP(+/+) but not
      in ICSBP(-/-) BMMs. Congruently, the expression of a major endosomal/lysosomal
      protease, cathepsin B, is strongly reduced in ICSBP(-/-) BMMs.

PMID- 11964286
TI  - A functional role of Stat3 in in vivo megakaryopoiesis.
AB  - The signal transducer and activator of transcription 3 (Stat3), a member of the
      Stat family of proteins, is commonly activated by thrombopoietic cytokines
      including thrombopoietin (TPO), interleukin (IL)-6, and interleukin-11. This
      finding strongly suggested that Stat3 has an important role in megakaryopoiesis
      and thrombopoiesis. To clarify the functional role of Stat3 in in vivo
      megakaryopoiesis and thrombopoiesis, we generated transgenic mice overexpressing
      a dominant-negative Stat3, Stat3F, to suppress the function of endogenous Stat3.
      To accomplish the selective expression of Stat3F in megakaryocytic lineage cells,
      we used the regulatory gene region of GATA-1 transcription factor selectively
      expressed in megakaryocytic and erythroid lineage cells. Two independent
      transgenic (Tg) mice lines were established. It was confirmed by Western blotting
      analysis that Stat3F proteins were highly expressed in the platelets from the Tg
      mice. In addition, it was found that Stat3 activation induced by TPO stimulation
      was drastically suppressed in these Tg mice compared with littermates. These
      findings indicate that Stat3F works well in the Tg mice. Platelet counts were
      within the normal range in steady-state conditions and were recovered normally
      from transient thrombocytopenia induced by antiplatelet serum injection.
      Interestingly, the platelet recovery from myelosuppression after 5-fluorouracil
      treatment was significantly delayed in the Tg mice. Collectively, our results
      strongly suggest that Stat3 plays an important role in the early stage of
      megakaryopoiesis, presumably through the expansion of megakaryocytic progenitor
      cells.

PMID- 11964287
TI  - Glycoprotein VI-mediated platelet fibrinogen receptor activation occurs through
      calcium-sensitive and PKC-sensitive pathways without a requirement for secreted
      ADP.
AB  - Collagen activates platelets by transducing signals through glycoprotein VI
      (GPVI). It is not clear whether collagen can directly activate fibrinogen
      receptors on the adherent platelets without a role for positive feedback
      agonists. We investigated the contribution of secondary G protein signaling to
      the mechanism of GPVI-stimulated platelet aggregation using the GPVI-selective
      agonists, convulxin and collagen-related peptide (CRP) as well as collagen.
      Adenosine diphosphate (ADP) scavengers or ADP receptor antagonists shifted the
      concentration-response curve slightly to the right at low concentrations of
      convulxin, whereas platelet aggregation at higher concentrations of convulxin was
      unaffected by these agents. ADP receptor antagonists shifted the concentration
      response curve of collagen- or CRP-induced platelet aggregation to the right at
      all the concentrations. Protein kinase C inhibitor, Ro 31-8220, or a calcium
      chelator 5,5'-dimethyl-BAPTA shifted the concentration-response curve of
      convulxin-induced platelet aggregation to the right. In addition, pretreatment
      with both Ro 31-8220 and dimethyl-BAPTA resulted in total inhibition of convulxin
      mediated aggregation. Blockade of either the calcium- or protein kinase C
      regulated pathway leads to inhibition of fibrinogen receptor activation on
      platelets adherent to collagen, but inhibition of both pathways leads to
      abolished fibrinogen receptor activation. We conclude that collagen-induced
      activation of fibrinogen receptor on adherent platelets through GPVI signaling
      occurs without any significant role for secreted ADP or thromboxane A(2).
      Furthermore, protein kinase C- and calcium-regulated pathways independently
      contribute to GPVI-mediated platelet aggregation.

PMID- 11964288
TI  - Antithrombotic effects of controlled inhibition of factor VIII with a partially
      inhibitory human monoclonal antibody in a murine vena cava thrombosis model.
AB  - The human monoclonal antibody mAb-LE2E9 partially inactivates human factor VIII
      (FVIII), leaving approximately 10% residual activity. The antithrombotic efficacy
      of the antibody was evaluated in mouse models of inferior vena cava thrombosis.
      Thrombi were induced in wild-type mice given either the antibody or saline. No
      thrombi occurred in any of 8 mice treated with mAb-LE2E9, whereas 6 of 8 control
      mice developed thrombi (P =.007). Treatment with mAb-LE2E9 did not result in a
      severe bleeding phenotype: a tail-cutting experiment that resulted in death of
      C57BL/6 FVIII-deficient (FVIII(-/-)) mice did not cause hemorrhagic death in mice
      treated with mAb-LE2E9. To evaluate the antithrombotic effect of mAb-LE2E9 in
      presence of human FVIII, thrombus formation was induced in FVIII(-/-) mice
      reconstituted intravenously with recombinant human FVIII (rhFVIII) or rhFVIII
      preincubated with mAb-LE2E9. Only 1 of 9 mice produced a thrombus in the
      rhFVIII/antibody complex-treated group, compared with 7 of 9 in the control group
      (P =.015). FVIII(-/-) mice were also reconstituted with rhFVIII and then injected
      with either mAb-LE2E9 or saline. One of 14 mice in the group treated with the
      antibody developed a thrombus, compared with 10 of 14 in the control group (P
      =.001). The thrombi occurring in antibody-treated animals were smaller than in
      controls (P <.01). All animals survived, and there were no bleeding
      complications. Thus, the mAb-LE2E9 antibody inhibits thrombosis without causing
      an overt bleeding tendency.

PMID- 11964289
TI  - A mouse orthologue of puromycin-insensitive leucyl-specific aminopeptidase is
      expressed in endothelial cells and plays an important role in angiogenesis.
AB  - Using polymerase chain reaction-coupled subtractive hybridization, we have
      isolated genes expressed during the in vitro differentiation of murine embryonic
      stem cells into endothelial cells (ECs). Among the genes obtained, we identified
      one gene that was inducible by vascular endothelial growth factor (VEGF) in the
      murine EC line MSS31. Analysis of the nucleotide and deduced amino acid sequences
      revealed that the protein was composed of 930 amino acids, including an
      HEXXH(X)18E consensus sequence of the M1 aminopeptidase family, and is thought to
      be a mouse orthologue of puromycin-insensitive leucyl-specific aminopeptidase
      (mPILSAP). The recombinant protein hydrolyzed N-terminal leucyl and methionyl
      residues from synthetic substrates. Immunohistochemical analysis revealed that
      mPILSAP was expressed in ECs during postnatal angiogenesis. Specific elimination
      of mPILSAP expression by antisense oligodeoxynucleotide (AS-ODN) attenuated VEGF
      stimulated proliferation, migration, and network formation of ECs in vitro.
      Moreover, AS-ODN to mPILSAP inhibited angiogenesis in vivo. These results suggest
      a novel function of mPILSAP, which is expressed in ECs and plays an important
      role in angiogenesis.

PMID- 11964290
TI  - Constitutive and functional association of the platelet collagen receptor
      glycoprotein VI-Fc receptor gamma-chain complex with membrane rafts.
AB  - The platelet collagen receptor glycoprotein (GP) VI-Fc receptor gamma-chain
      (FcRgamma) complex transduces signals in an immunoreceptorlike manner. We
      examined a role for the Triton X-100-insoluble membrane rafts in GPVI-FcRgamma
      complex signaling. Methyl-beta-cyclodextrin (MbetaCD)-induced disruption of the
      membrane rafts inhibited not only platelet aggregation and secretion but also
      tyrosine phosphorylation of signaling molecules on stimulation through the GPVI
      FcRgamma complex. The GPVI-FcRgamma complex was constitutively associated with
      membrane rafts wherein the Src family kinases and LAT were also present. Their
      association was not affected by the complex engagement but was highly sensitive
      to MbetaCD treatment. Thus, we provide the first evidence that the GPVI-FcRgamma
      complex is constitutively and functionally associated with membrane rafts.

PMID- 11964291
TI  - Alanine-170 and proline-172 are critical determinants for extracellular CD20
      epitopes; heterogeneity in the fine specificity of CD20 monoclonal antibodies is
      defined by additional requirements imposed by both amino acid sequence and
      quaternary structure.
AB  - In vivo ablation of malignant B cells can be achieved using antibodies directed
      against the CD20 antigen. Fine specificity differences among CD20 monoclonal
      antibodies (mAbs) are assumed not to be a factor in determining their efficacy
      because evidence from antibody-blocking studies indicates limited epitope
      diversity with only 2 overlapping extracellular CD20 epitopes. However, in this
      report a high degree of heterogeneity among antihuman CD20 mAbs is demonstrated.
      Mutation of alanine and proline at positions 170 and 172 (AxP) (single-letter
      amino acid codes; x indicates the identical amino acid at the same position in
      the murine and human CD20 sequences) in human CD20 abrogated the binding of all
      CD20 mAbs tested. Introduction of AxP into the equivalent positions in the murine
      sequence, which is not otherwise recognized by antihuman CD20 mAbs, fully
      reconstituted the epitope recognized by B1, the prototypic anti-CD20 mAb. 2H7, a
      mAb previously thought to recognize the same epitope as B1, did not recognize the
      murine AxP mutant. Reconstitution of the 2H7 epitope was achieved with additional
      mutations replacing VDxxD in the murine sequence for INxxN (positions 162-166 in
      the human sequence). The integrity of the 2H7 epitope, unlike that of B1, further
      depends on the maintenance of CD20 in an oligomeric complex. The majority of 16
      antihuman CD20 mAbs tested, including rituximab, bound to murine CD20 containing
      the AxP mutations. Heterogeneity in the fine specificity of these antibodies was
      indicated by marked differences in their ability to induce homotypic cellular
      aggregation and translocation of CD20 to a detergent-insoluble membrane
      compartment previously identified as lipid rafts.

PMID- 11964292
TI  - Type I interferons produced by dendritic cells promote their phenotypic and
      functional activation.
AB  - Resting dendritic cells (DCs) are resident in most tissues and can be activated
      by environmental stimuli to mature into potent antigen-presenting cells. One
      important stimulus for DC activation is infection; DCs can be triggered through
      receptors that recognize microbial components directly or by contact with
      infection-induced cytokines. We show here that murine DCs undergo phenotypic
      maturation upon exposure to type I interferons (type I IFNs) in vivo or in vitro.
      Moreover, DCs either derived from bone marrow cells in vitro or isolated from the
      spleens of normal animals express IFN-alpha and IFN-beta, suggesting that type I
      IFNs can act in an autocrine manner to activate DCs. Consistent with this idea,
      the ability to respond to type I IFN was required for the generation of fully
      activated DCs from bone marrow precursors, as DCs derived from the bone marrow of
      mice lacking a functional receptor for type I IFN had reduced expression of
      costimulatory and adhesion molecules and a diminished ability to stimulate naive
      T-cell proliferation compared with DCs derived from control bone marrow.
      Furthermore, the addition of neutralizing anti-IFN-alpha/beta antibody to
      purified splenic DCs in vitro partially blocked the "spontaneous" activation of
      these cells, inhibiting the up-regulation of costimulatory molecules, secretion
      of IFN-gamma, and T-cell stimulatory activity. These results show that DCs both
      secrete and respond to type I IFN, identifying type I interferons as autocrine DC
      activators.

PMID- 11964293
TI  - Humoral immune responses against Wilms tumor gene WT1 product in patients with
      hematopoietic malignancies.
AB  - Wilms tumor gene WT1 is expressed at high levels in hematopoietic malignancies,
      such as leukemias and myelodysplastic syndromes (MDS), and in various kinds of
      solid tumors, including lung cancer, and it exerts an oncogenic function in these
      malignancies. IgM and IgG WT1 antibodies were measured by means of dot blot assay
      in 73 patients with hematopoietic malignancies (16 acute myeloid leukemia [AML],
      11 acute lymphoid leukemia [ALL], 13 chronic myeloid leukemia [CML], and 33 MDS)
      and 43 healthy volunteers. Immunoglobulin IgM, IgG, and IgM+IgG WT1 antibodies
      were detected in 40 (54.8%), 40 (54.8%), and 24 (32.8%), respectively, of the 73
      patients with hematopoietic malignancies, whereas 7 (16.2%), 2 (4.7%), and none
      of the 43 healthy volunteers had IgM, IgG, or IgM+IgG WT1 antibodies,
      respectively. Furthermore, immunoglobulin isotype class switching of WT1
      antibodies from IgM to IgG occurred in conjunction with disease progression from
      refractory anemia (RA) to RA with excess of blasts (RAEB), and further to RAEB in
      transformation (RAEB-t) in MDS patients. These results showed that humoral immune
      responses against the WT1 protein could be elicited in patients with WT1
      expressing hematopoietic malignancies, and they suggested that the helper T-cell
      responses needed to induce humoral immune responses and immunoglobulin isotype
      class switching from IgM to IgG were also generated in these patients. Our
      findings may provide new insight into the rationale for elicitation of cytotoxic
      T-cell responses against the WT1 protein in cancer immunotherapy using the WT1
      vaccine.

PMID- 11964294
TI  - Tumor lysate-specific cytotoxic T lymphocytes in multiple myeloma: promising
      effector cells for immunotherapy.
AB  - The idiotype protein, secreted by myeloma plasma cells, is a tumor-specific but
      weak antigen. Idiotype-based immunotherapy has been explored in myeloma patients
      with disappointing results. It is conceivable that myeloma cells contain a
      multitude of tumor antigens that can more effectively stimulate antitumor T
      cells. To explore the possibility of using whole myeloma cells as a source of
      tumor antigens for immunotherapy, the current study was undertaken to generate
      and examine the function of myeloma-specific cytotoxic T lymphocytes (CTLs) by
      using dendritic cells (DCs) pulsed with myeloma cell lysates as stimulating
      cells. After repeated stimulation, specific CTL lines, containing CD4(+) and
      CD8(+) T cells, were generated from myeloma patients. Our results show that these
      T cells not only recognized and lysed autologous myeloma protein-pulsed DCs, they
      also killed autologous primary myeloma cells. Occasionally, CTLs responded to
      autologous idiotype-pulsed DCs and to allogeneic primary myeloma cells. No
      cytolytic activity, however, was detected against autologous lymphocytes
      including B cells, suggesting that the T cells acted specifically against myeloma
      cells. Cytotoxicity against target cells was major histocompatibility complex
      class 1 and, to a lesser extent, class 2 restricted and was dependent mainly on
      the perforin-mediated pathway. CTLs secreted predominantly interferon-gamma and
      tumor necrosis factor-alpha on antigenic stimulation, indicating a type 1 T-cell
      subset. These findings represent the first demonstration that tumor cell lysate
      primed CTLs kill only myeloma cells, not autologous lymphocytes. This provides a
      rationale for myeloma cell-based immunotherapy in multiple myeloma.

PMID- 11964295
TI  - HLA-B7 beta-pleated sheet-derived synthetic peptides are immunodominant T-cell
      epitopes regulating alloresponses.
AB  - Chronic rejection of transplanted allografts is the major cause of graft loss
      after clinical solid organ transplantation. Recent data link the indirect
      presentation of allopeptides to chronic graft loss; thus, identification of
      immunodominant epitopes on major histocompatibility complex (MHC) antigens could
      significantly contribute to establishing novel ways for monitoring and managing
      chronic rejection. Here, we show that synthetic allo-MHC-derived peptides
      covering the polymorphic region 56 to 120 of HLA-B7 modulate alloresponses. In
      particular, the 2 beta-pleated sheet-derived peptides covering residues 91 to 105
      and 96 to 120, respectively, but not sequences from the alpha1 helix, were
      presented by autologous peripheral blood lymphocytes to induce T-cell
      proliferation. In addition, the 2 beta-pleated sheet-derived peptides and the
      alpha1-derived peptide residues 60 to 75 abrogated lysis of HLA-B7 target cells
      by anti-HLA-B7 cytotoxic T lymphocytes (CTLs). Although most residues between 91
      and 120 are normally not directly accessible to T cells, our results indicate
      that peptides derived from the lower surface of the peptide-binding groove of HLA
      B7 are immunodominant in HLA-B7 alloresponses. To characterize the binding and
      stability of allopeptides to T cells, the 62-70 peptide-derived from the 60-75
      allopeptide that blocked cytotoxicity of anti-HLA-B7 CTL-was synthesized and
      coupled with fluorescein isothiocyanate. The peptide specifically labeled anti-B7
      CTL, but not anti-HLA-A2 CTL as measured by flow cytometry. Peptide binding to
      CTL was specific at 4 degrees C and remained stable for 12 hours, whereas it
      remained stable for less than 2 hours at 37 degrees C. These studies allow the
      identification of HLA-B7 T-cell epitopes and reveal for the first time a novel,
      previously unrecognized application of synthetic HLA-derived allopeptides to
      visualize alloreactive T cells.

PMID- 11964296
TI  - Human immune associated nucleotide 1: a member of a new guanosine triphosphatase
      family expressed in resting T and B cells.
AB  - TAL-1 is a basic helix-loop-helix oncoprotein that is expressed in up to 30% of T
      cell acute lymphoblastic leukemias but not in the T lineage. We have cloned a
      complementary DNA, called Human Immune Associated Nucleotide 1 (hIAN1), whose
      messenger RNA (mRNA) level expression is inversely correlated to the TAL-1 mRNA
      level in human leukemic T-cell lines. The hIAN1 encodes a 38-kd protein that
      belongs to a novel family of proteins conserved from plants to humans and
      characterized by motifs related to, but highly divergent from, the consensus
      motifs found in guanosine triphosphate (GTP)-binding proteins. Despite these
      divergent amino acids at positions involved in GTP/guanosine diphosphate (GDP)
      binding and guanosine triphosphatase (GTPase) activities, we found that hIAN1
      specifically binds GDP (K(d) = 0.47 microM) and GTP (K(d) = 6 microM) and
      exhibits intrinsic GTPase activity. Among mature hematopoietic cells, hIAN1 is
      specifically expressed in resting T and B lymphocytes, and its expression level
      tremendously decreased at the protein but not the mRNA level during B- or T
      lymphocyte activation, suggesting a specific role for this new type of GTPase
      during the immune response.

PMID- 11964297
TI  - Cytokine production and cytolytic mechanism of CD4(+) cytotoxic T lymphocytes in
      ex vivo expanded therapeutic Epstein-Barr virus-specific T-cell cultures.
AB  - Ex vivo expanded Epstein-Barr virus (EBV)-specific T cells have been successfully
      applied clinically for adoptive immunotherapy. However, the role of CD4(+) T
      cells in the therapeutic T-cell culture has not been established for the
      reconstitution of EBV-specific immunity. We isolated and characterized CD4(+) T
      cell lines from the ex vivo T-cell cultures. Monoclonal line PD-F4 and
      oligoclonal lines ND-R4 and TD-B4 were CD3(+)CD4(+)CD8(-). Cytolytic tests with
      targets of mismatched major histocompatibility complex (MHC) and anti-MHC
      antibodies confirmed that the cytotoxicity of these CD4(+) cells was restricted
      by MHC class II. Single cells of ND-R4 expressed interferon-gamma (IFN-gamma, or
      interleukin 4 (IL-4), but rarely coexpressed these 2 cytokines. In contrast, PD
      F4 coexpressed IFN-gamma, IL-2, and IL-4. Kinetic studies with PD-F4 showed that
      expression of the 3 cytokines plateaued 5 hours upon stimulation and was then
      drastically reduced, with a pattern consistent with independent modulation and
      differential off-cycle signal requirements. The cytotoxicity of these CD4(+)
      cells was largely resistant to brefeldin A, an inhibitor for cytolytic pathways
      by Fas-ligand family molecules. Although sensitive to concanamycin A and
      ethyleneglycotetraacetic acid, which inhibit cytotoxicity by granule exocytosis,
      the CD4(+) cytotoxic T lymphocytes (CTLs) did not express perforin, suggesting a
      cytotoxic mechanism independent of perforin although involving exocytosis. Flow
      cytometric analysis showed that the CD4(+) CTLs expressed granulysin, a recently
      identified cytolytic molecule associated with exocytotic cytolytic granules.
      These data suggested that CD4(+) T cells in the therapeutic B-lymphoblastoid cell
      lines-primed T-cell culture are diverse in producing T(H)1 and T(H)2 cytokines,
      and may exert specific cytotoxicity via exocytosis of granulysin.

PMID- 11964298
TI  - Interleukin-7-treated naive T cells can be productively infected by T-cell
      adapted and primary isolates of human immunodeficiency virus 1.
AB  - Although human immunodeficiency virus (HIV) gag/pol DNA can be detected in naive
      T cells, whether naive T cells can be productively infected by HIV is still
      questionable. Given that interleukin-7 (IL-7) is a prospective therapeutic
      immunomodulator for the treatment of HIV, we evaluated the effect of IL-7 on
      promoting naive T-cell infection of laboratory-adapted (IIIB), M-tropic, and
      primary isolates of HIV. Initially, we determined that the 3 cell surface markers
      widely used to identify naive T cells (CD45RA(+)CD45RO(-), CD45RA(+)CD62L(+), and
      CD45RO(-)CD27(+)CD95(low)) are all equivalent in T-cell receptor excision circle
      content, a marker for the replicative history of a cell as well as for de novo T
      cells. We therefore used CD45RA(+)CD45RO(-) expression to define naive T cells in
      this study. We demonstrate that although untreated or IL-2-treated naive T cells
      are not productively infected by HIV, IL-7 pretreatment mediated the productive
      infection of laboratory-adapted, M-tropic, and primary isolates of HIV as
      determined by p24 core antigen production. This up-regulation was between 8- and
      58-fold, depending on the HIV isolate used. IL-7 pretreatment of naive T cells
      also potently up-regulated surface expression of CXCR4 but not CCR5 and mediated
      the expansion of naive T cells without the acquisition of the primed CD45RO
      phenotype. Collectively, these data indicate that IL-7 augments naive T-cell
      susceptibility to HIV and that under the appropriate environmental milieu, naive
      T cells may be a source of HIV productive infection. This information needs to be
      considered in evaluating IL-7 as an immunomodulator for HIV-infected patients.

PMID- 11964300
TI  - Heavy chain ferritin activates regulatory T cells by induction of changes in
      dendritic cells.
AB  - Heavy chain ferritin (H-ferritin) is a component of the iron-binding protein,
      ferritin. We have previously shown that H-ferritin inhibits anti-CD3-stimulated
      lymphocyte proliferation and that this was due to increased production of
      interleukin-10 (IL-10). In the present study we have shown that induction of IL
      10 production was due to effects of H-ferritin on adherent antigen-presenting
      cells (APCs) in blood and monocyte-derived dendritic cells (MoDCs). IL-10 was
      produced by a subpopulation of CD4 T cells, which expressed the CD25 component of
      the IL-2 receptor and the CTLA-4 receptor characteristic of regulatory T cells.
      The changes induced in MoDCs were compared with those induced by CD40L and their
      significance tested by inhibition with monoclonal antibodies. These studies
      indicated that H-ferritin induced relatively greater expression of CD86 and B7-H1
      on MoDCs and that monoclonal antibodies against their receptors, CTLA-4 and
      programmed death receptor-1 (PD-1), inhibited IL-10 production from the
      regulatory T cells. H-ferritin did not appear to induce direct production of the
      cytokines IL-2, IL-4, IL-6, IL-10, IL-12, or interferon-gamma from the DCs. These
      results are consistent with the thesis that H-ferritin induces B7-H1 and CD86 (B7
      2) on APCs, which in turn induce IL-10 production from regulatory T cells. This
      is possibly one mechanism by which melanoma cells may induce changes in APCs in
      the vicinity of the tumor and result in suppression of immune responses by
      induction of regulatory T cells.

PMID- 11964299
TI  - Human primary and memory cytotoxic T lymphocyte responses are efficiently induced
      by means of CD40-activated B cells as antigen-presenting cells: potential for
      clinical application.
AB  - CD40 engagement is the major signal that induces B cells to efficiently present
      antigen to T cells. We previously demonstrated that human peripheral blood
      derived CD40-activated B cells (CD40-B cells) function as antigen-presenting
      cells (APCs). Here, we have established a culture system to generate these APCs
      under clinically applicable conditions using guanylic acid-grade soluble trimeric
      CD40 ligand. To monitor APC function and antigen loading for these cells, simple
      and efficient quality control assays have been developed. Using this approach, we
      demonstrate that CD40-B cells from healthy donors and cancer patients are fully
      functional and equally expanded in long-term cultures. These B cells boost robust
      memory T-cell responses, but more importantly, they also prime naive T-cell
      responses against neoantigens ex vivo. CD40-B cells overcome current obstacles,
      such as the difficulty of isolation, generation, and long-term expansion observed
      with other APCs. Therefore, they are an excellent source of professional APCs for
      immune assessment, antigen discovery, and antigen-specific immunotherapy.

PMID- 11964302
TI  - Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced
      chemotaxis: contribution of src family kinase and PI3-kinase on calcium
      mobilization and cell migration.
AB  - Stem cell factor (SCF) has crucial roles in proliferation, survival, and
      differentiation of hematopoietic stem cells and mast cells through binding to c
      Kit receptor (KIT). Chemotaxis is another unique function of SCF. However, little
      is known about the intracellular signaling pathway of SCF/KIT-mediated cell
      migration. To investigate the signaling cascade, we made a series of 22 KIT
      mutants, in which tyrosine (Y) residue was substituted for phenylalanine (F) in
      the cytoplasmic domain, and introduced into BAF3 cells or 293T cells. On
      stimulation with SCF, BAF3 expressing KIT(WT)(WT) showed cell migration and
      Ca(2+) mobilization. Among 22 YF mutants, Y567F, Y569F, and Y719F showed
      significantly reduced cell migration and Ca(2+) mobilization compared to WT. In
      Y567F, Lyn activation on SCF stimulation decreased and C-terminal Src kinase
      (Csk) suppressed KIT-mediated Ca(2+) influx and cell migration, suggesting that
      Y567-mediated Src family kinase (SFK) activation leads to Ca(2+) influx and
      migration. Furthermore, we found that p38 mitogen-activated protein kinase (p38
      MAPK) and Erk1/2 were also regulated by Y567/SFK and involved in cell migration,
      and that p38 MAPK induced Ca(2+) influx, thereby leading to Erk1/2 activation. In
      Y719F, the binding of phosphatidylinositol 3'-kinase (PI3K) to KIT was lost and
      KIT-mediated cell migration and Ca(2+) mobilization were suppressed by PI3K
      chemical inhibitors or dominant-negative PI3K, suggesting the involvement of Y719
      mediated PI3K pathway in cell migration. Combination of Csk and the PI3K
      inhibitor synergistically reduced cell migration, suggesting the cooperation of
      SFK and PI3K. Taken together, these results indicate that 2 major KIT signaling
      pathways lead to cell migration, one is Y567-SFK-p38 MAPK-Ca(2+) influx-Erk and
      the other is Y719-PI3K-Ca(2+) influx.

PMID- 11964301
TI  - High frequencies of Th1-type CD4(+) T cells specific to HTLV-1 Env and Tax
      proteins in patients with HTLV-1-associated myelopathy/tropical spastic
      paraparesis.
AB  - CD4(+) T cells are critical for inducing and maintaining efficient humoral and
      cellular immune responses to pathogens. The CD4(+) T-cell response in human T
      lymphotropic virus 1 (HTLV-1) infection has not been studied in detail. However,
      CD4(+) T cells have been shown to predominate in early lesions in HTLV-1
      associated myelopathy/tropical spastic paraparesis (HAM/TSP). We present direct
      estimates of HTLV-1 Env- and Tax-specific CD4(+) T-cell frequencies in patients
      infected with HTLV-1. We first showed that there was a strong bias toward the Th1
      phenotype in these HTLV-1-specific CD4(+) T cells in patients with HAM/TSP. We
      then demonstrated significantly higher frequencies of HTLV-1-specific Th1-type
      CD4(+) T cells in HAM/TSP patients than in asymptomatic HTLV-1 carriers. The
      majority of these HTLV-1-specific CD4(+) T cells did not express HTLV-1 Tax and
      were therefore unlikely to be infected by HTLV-1. High frequencies of activated
      HTLV-1-specific CD4(+) T cells of the Th1 phenotype might contribute to the
      initiation or pathogenesis of HAM/TSP and other HTLV-1-associated inflammatory
      diseases.

PMID- 11964303
TI  - Perturbation of B-cell development in mice overexpressing the Bcl-2 homolog A1.
AB  - Decisions about cell survival or death are central components of adaptive
      immunity and occur at several levels in immune system development and function.
      The Bcl-2 family of homologous proteins plays an important role in these
      decisions in lymphoid cells. Bcl-2, Bcl-xL, and A1 are differentially expressed
      during B- and T-cell development, and they have shared and distinct roles in
      regulating cell death. We sought to gain insight into the role of A1 in immune
      system development and function. A murine A1-a transgene was expressed under the
      control of the Emu enhancer, and mice with A1 overexpression in B- and T-cell
      lineages were derived. Thymocytes and early B cells in Emu-A1 mice showed
      extended survival. B-lineage development was altered, with expansion of the pro-B
      cell subset at the expense of pre-B cells, suggesting an impairment of the pro-
      to pre-B-cell transition. This early B-cell phenotype resembled Emu-Bcl-xL mice
      but did not preferentially rescue cells with completed V(D)J rearrangements of
      the immunoglobulin heavy chain. In contrast to Emu-Bcl-2 transgenes, A1
      expression in pro-B cells did not rescue pre-B-cell development in SCID mice.
      These studies indicate that A1 protects lymphocytes from apoptosis in vitro but
      that it has lineage- and stage-specific effects on lymphoid development.
      Comparison with the effects of Bcl-2 and Bcl-xL expressed under similar control
      elements supports the model that antiapoptotic Bcl-2 homologs interact
      differentially with intracellular pathways affecting development and apoptosis in
      lymphoid cells.

PMID- 11964304
TI  - Identification of an HLA A*0201-restricted CD8(+) T-cell epitope for the
      glycoprotein B homolog of human herpesvirus 8.
AB  - Human herpesvirus 8 (HHV-8; Kaposi sarcoma-associated herpesvirus)-specific
      cytotoxic T-lymphocyte (CTL) and interferon-gamma (IFN-gamma) responses to
      proteins produced during the lytic cycle of HHV-8 replication are mediated by HLA
      class I-restricted, CD8(+) T cells. We have characterized the fine specificity of
      the CD8(+) T-cell response to 25 peptides derived from 5 HHV-8 lytic cycle
      proteins based on a prediction model for HLA A*0201 binding motifs. One of the 25
      HLA A*0201 peptides derived from the glycoprotein B (gB) homolog of Epstein-Barr
      virus (gB(492-500); LMWYELSKI; single-letter amino acid codes) bound to HLA
      A*0201 and stimulated IFN-gamma responses in CD8(+) T cells from HHV-8(+), HLA
      A*0201 persons, but not HHV-8-seronegative or non-HLA A*0201 persons. The peptide
      also induced IFN-gamma and CTL reactivity to naturally processed gB protein. The
      peptide was a major immunogenic epitope of HHV-8 as indicated by induction of IFN
      gamma responses in peripheral blood mononuclear cells from 5 of 5 HHV-8
      seropositive, HLA A*0201 persons when gB(492-500) was presented by autologous
      dendritic cells. T-cell reactivity to gB(492-500) was not related to detectable
      HHV-8 DNA in the blood. These data show that CD8(+) T cells recognize an HLA
      A*0201-restricted epitope for HHV-8 lytic cycle protein gB, particularly when
      presented by dendritic cells. This epitope may be important in control of HHV-8
      infection by CD8(+) T cells.

PMID- 11964305
TI  - MDM2 induces NF-kappaB/p65 expression transcriptionally through Sp1-binding
      sites: a novel, p53-independent role of MDM2 in doxorubicin resistance in acute
      lymphoblastic leukemia.
AB  - MDM2 protein is thought to exhibit tumorigenic activity by binding to the p53
      tumor-suppressor protein and inhibiting its function. Alternatively, MDM2 may
      have oncogenic roles other than those resulting from p53 interactions. Here we
      report that MDM2 can induce expression of the p65 subunit of NF-kappaB, which is
      an anti-apoptotic factor expressed in certain neoplastic cells in response to
      chemotherapy. Initially, we noted that the overexpression of MDM2 protein in
      leukemic bone marrow cells of patients with B-cell precursor acute lymphoblastic
      leukemia (BCP-ALL), and an ALL cell line (EU-4) transfected with the MDM2 gene
      was associated with elevated expression of p65 and in vitro resistance to
      doxorubicin (Adriamycin). By cotransfection of the MDM2 gene and p65-promoter
      reporter constructs into EU-4 cells, we found that transient and high-level MDM2
      expression induced p65 promoter activity. In the presence of wild-type (wt) p53,
      MDM2 increased p65 promoter activity by reversing p53-mediated suppression of
      p65. In the absence of p53, MDM2 directly increased p65 promoter activity.
      Deletion and mutation analysis of the p65 promoter indicated that the region
      between nt -575 and -178, which contains the first and second Sp1-binding sites,
      was required for activation by MDM2. Further studies using chromatin
      immunoprecipitation (CHIP) and electrophoretic mobility shift assay (EMSA) showed
      that MDM2 was able to directly bind to the Sp1 site of the p65 promoter. Our
      findings suggest that by inducing p65 expression, MDM2 has a p53-independent role
      in tumorigenesis, which may further elucidate the association between MDM2
      overexpression and resistant disease in childhood ALL.

PMID- 11964306
TI  - In situ localization of follicular lymphoma: description and analysis by laser
      capture microdissection.
AB  - From 1992 to 2000, we identified 23 lymph node biopsies with focal germinal
      centers (GCs) containing centrocytes staining strongly for bcl-2 protein, whereas
      most of the remaining lymph node showed bcl-2-negative follicular hyperplasia. We
      propose the designation in situ localization of follicular lymphoma (FL) for this
      phenomenon. In 2 additional cases, bcl-2(+) follicles with features of in situ FL
      were identified in association with other low-grade B-cell lymphomas. To
      investigate the clonality of the bcl-2(+) follicles, we performed laser capture
      microdissection of bcl-2(+) and bcl-2 follicles from the same lymph node in 5
      cases, and analyzed them in parallel by polymerase chain reaction (PCR)
      amplification of immunoglobulin heavy chain (IgH) genes. In 4 of 5 cases the bcl
      2(+) follicles contained monoclonal IgH gene rearrangements, whereas the bcl-2(-)
      GCs exhibited a polyclonal ladder. A BCL2/JH gene rearrangement was detected in 6
      of 14 (43%) evaluable cases. There were 5 patients with synchronous evidence of
      FL at another site. There were 13 patients who, without a prior diagnosis of FL,
      had clinical follow-up; one developed FL in an adjacent lymph node within one
      year, and 2 manifested FL at 13 and 72 months, respectively. There are 10
      patients who have not yet shown other evidence of FL. These results suggest that
      at least close to half of these cases (8/18; 44%) represent homing to and early
      colonization of reactive GCs by FL. Other cases might represent FL at the
      earliest stage of development, or a preneoplastic event, requiring a second hit
      for neoplastic transformation. These findings provide insight into the
      pathophysiology of early FL, and illustrate the utility of immunohistochemistry
      for early diagnosis.

PMID- 11964307
TI  - Human T-cell lymphotropic virus type 1-transformed cells induce angiogenesis and
      establish functional gap junctions with endothelial cells.
AB  - The role of angiogenesis in the growth and metastasis of solid tumors is well
      established. However, the role of angiogenesis in hematologic malignancies was
      only recently appreciated. We show that HTLV-I-transformed T cells, but not HTLV
      I-negative CD4(+) T cells, secrete biologically active forms of vascular
      endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and,
      accordingly, induce angiogenesis in vitro. Furthermore, fresh ATL leukemic cells
      derived from patients with acute ATL produce VEGF and bFGF transcripts and
      proteins. The viral transactivator Tax activates the VEGF promoter, linking the
      induction of angiogenesis to viral gene expression. Angiogenesis is associated
      with the adhesion of HTLV-I-transformed cells to endothelial cells and gap
      junction-mediated heterocellular communication between the 2 cell types.
      Angiogenesis, cell adhesion, and communication likely contribute to the
      development of adult T-cell leukemia-lymphoma and represent potential therapeutic
      targets.

PMID- 11964308
TI  - Inhibition of PDE4 phosphodiesterase activity induces growth suppression,
      apoptosis, glucocorticoid sensitivity, p53, and p21(WAF1/CIP1) proteins in human
      acute lymphoblastic leukemia cells.
AB  - Glucocorticoids are integral to successful treatment of childhood acute
      lymphoblastic leukemia (ALL) and other lymphoid malignancies. A large body of
      data indicates that in various model systems, elevation of cyclic adenosine
      monophosphate (cAMP) can potentiate glucocorticoid response, although this has
      not been well evaluated as a potential leukemia treatment. Although cAMP analogs
      have been studied, little data exist regarding the potential toxicity to leukemia
      cells of pharmacologic elevation of cAMP levels in leukemic blasts. Using MTT
      assays of cell proliferation on CEM ALL cells, we found that aminophylline and
      other nonspecific phosphodiesterase (PDE) inhibitors suppress cell growth. This
      effect is replicated by the PDE4-specific PDE inhibitor rolipram, but not by
      specific inhibitors of the PDE1 or PDE3 classes. We found that PDE inhibitors
      cause increased dexamethasone sensitivity and a synergistic effect with the
      adenylyl cyclase activator forskolin. We observed several important cellular
      characteristics associated with this treatment, including elevation of cAMP,
      induction of p53 and p21(WAF1/CIP1) proteins, G(1) and G(2)/M cell cycle arrest,
      and increased apoptosis. Sensitivity to forskolin and rolipram is shared by at
      least 2 pediatric ALL cell lines, CEM and Reh cells. Some cell lines derived from
      adult-type lymphoid malignancies also show sensitivity to this treatment. These
      findings suggest that PDE inhibitors have therapeutic potential in human ALL and
      characterize the molecular mechanisms that may be involved in this response.

PMID- 11964310
TI  - Interactions of GATA-2 with the promyelocytic leukemia zinc finger (PLZF)
      protein, its homologue FAZF, and the t(11;17)-generated PLZF-retinoic acid
      receptor alpha oncoprotein.
AB  - Transcription factor GATA-2 is implicated in the survival and growth of
      multipotential progenitors. Here we report that the promyelocytic leukemia zinc
      finger (PLZF) protein can interact with GATA-2 and can modify its transactivation
      capacity. Fanconi anemia zinc finger (FAZF), a PLZF-homologous protein that has
      been variously described as ROG (repressor of GATA), and TZFP (testis zinc finger
      protein) also interact with GATA-2. The zinc finger region of GATA-2 is required
      for binding to PLZF and FAZF, but distinct interfaces on the PLZF and FAZF
      molecules mediate the interaction, suggesting that GATA-2 activity is controlled
      by these 2 homologous proteins through distinct mechanisms. GATA-2 can also
      physically associate with the PLZF-RARalpha fusion protein generated by the
      t(11;17) chromosomal translocation associated with acute promyelocytic leukemia
      (APL). Functional experiments showed that this interaction has the capacity to
      render GATA-dependent transcription responsive to treatment with a combination of
      all-trans retinoic acid and the histone deacetylase inhibitor trichostatin A
      (TSA). This combination of drugs has been shown to stimulate the terminal
      differentiation of leukemic t(11;17)-associated APL blasts, raising the
      possibility that GATA target genes may be involved in the molecular pathogenesis
      of APL.

PMID- 11964309
TI  - Activated Notch1 signaling promotes tumor cell proliferation and survival in
      Hodgkin and anaplastic large cell lymphoma.
AB  - Notch signaling controls cell fate decisions of hematopoietic progenitors by
      inhibiting certain steps of differentiation and inducing either self-renewal or
      differentiation toward lymphoid or myeloid lineages. In addition, truncated
      Notch1 alleles could be associated with 10% of all cases of human T lymphoblastic
      leukemia and, when introduced into mouse bone marrow stem cells, cause T-cell
      neoplasms. However, functional links between the abundant expression of intact
      Notch1 and oncogenesis are still lacking. Here we show that Notch1 is highly
      expressed in B- and T-cell-derived tumor cells of Hodgkin and anaplastic large
      cell lymphoma. We demonstrate a novel mechanism for the oncogenic capacity of
      Notch1 by showing that the interaction between intact Notch1 on tumor cells and
      its ligand Jagged1 dramatically induces proliferation and inhibition of apoptosis
      in vitro. We further provide evidence that in Hodgkin and anaplastic large cell
      lymphoma, Jagged1 is expressed in malignant and in bystander cells colocalizing
      with Notch1-positive tumor cells. Notch1 signaling may therefore be activated in
      tumor cells by Jagged1 through homotypic or heterotypic cell-cell interactions,
      and it seems likely that these interactions contribute to lymphomagenesis in
      vivo. Thus, our data suggest that activated Notch1 signaling plays an important
      role in the pathobiology of Hodgkin and anaplastic large cell lymphoma and that
      it might be a potential new target for treatment.

PMID- 11964311
TI  - Population depletion activates autonomous CD154-dependent survival in biopsylike
      Burkitt lymphoma cells.
AB  - Population size is governed through cells reacting to a variety of intrinsic and
      extrinsic cues. Tumors, while liberated from many of the homeostatic constraints
      placed on physiologic counterparts, can nonetheless remain subject to both social
      and environmental control. Burkitt lymphoma cells faithful to the biopsy
      phenotype were used to model the reliance of the colony, if any, on an inbuilt
      population sensor. Below a normally suicidal threshold number of cells, low
      picomolar quantities of exogenous CD40 ligand (CD40L/CD154) were found to sustain
      the clone without the discernible shift in phenotype that accompanies high CD40L
      encounter. Although CD154 was undetectable in populous cultures, message was
      induced as numbers became limiting. Correspondingly, attempts to neutralize
      endogenous CD40L activity failed to perturb cells at optimal densities but
      resulted in their marked decline as the critical threshold was approached. These
      data reveal an auto-inducible survival mechanism seemingly regulated through the
      monitoring of population size, a process somewhat akin to that of "quorum
      sensing" among gram-negative bacteria in which diffusible molecules provide a
      means of communication to coordinate gene expression with population density.
      This process could be activated as cells discern depletions in their community or
      when deprived of signals otherwise furnished within an appropriate environmental
      niche.

PMID- 11964312
TI  - Ectopic overexpression of second mitochondria-derived activator of caspases
      (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates
      epothilone B derivative-(BMS 247550) and Apo-2L/TRAIL-induced apoptosis.
AB  - Second mitochondria-derived activator of caspases (Smac)/DIABLO is a
      mitochondrial protein that is released into the cytosol along with cytochrome c
      (cyt c) during the execution of the intrinsic pathway of apoptosis. Smac/DIABLO
      promotes apoptosis by neutralizing the inhibitory effect of the inhibitor of
      apoptosis (IAP) family of proteins on the processing and activities of the
      effector caspases. Present studies demonstrate that, upon engagement of the
      mitochondrial pathway of apoptosis, epothilone (Epo) B derivative BMS 247550, a
      novel nontaxane antimicrotubule agent, as well as the death ligand Apo-2L/TRAIL
      (tumor necrosis factor-alpha-related apoptosis-inducing ligand) induce the
      mitochondrial release and cytosolic accumulation of Smac/DIABLO, along with cyt
      c, in human acute leukemia Jurkat T cells. While it had no activity alone,
      ectopic overexpression of Smac/DIABLO or treatment with the N-terminus
      heptapeptide (Smac-7) or tetrapeptide (Smac-4) of Smac/DIABLO significantly
      increased Epo B- or Apo-2L/TRAIL-induced processing and PARP cleavage activity of
      caspase-3. This produced a significant increase in apoptosis of Jurkat cells (P
      <.05). Increased apoptosis was also associated with the down-regulation of XIAP,
      cIAP1, and survivin. Along with the increased activity of caspase-3, ectopic
      overexpression of Smac/DIABLO or cotreatment with Smac-4 also increased Epo B- or
      Apo-2L/TRAIL-induced processing of caspase-8 and Bid, resulting in enhanced
      cytosolic accumulation of cyt c. This was not due to increased assembly and
      activity of Apo-2L/TRAIL-induced DISC (death-inducing signaling complex) but
      dependent on the feedback activity of caspase-3. These findings demonstrate that
      cotreatment with the N-terminus Smac/DIABLO peptide is an effective strategy to
      enhance apoptosis triggered by the death receptor or mitochondrial pathway and
      may improve the antitumor activity of Apo-2L/TRAIL and Epo B.

PMID- 11964313
TI  - Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by
      interferon-gamma: a molecular basis for priming and synergism with bacterial
      lipopolysaccharide.
AB  - In human monocytes and macrophages, interferon-gamma (IFNgamma) augmented mRNA
      and surface expression of toll-like receptor 4 (TLR4), a crucial component of the
      signaling receptor complex for bacterial lipopolysaccharide (LPS). Expression of
      the accessory component MD-2 and of the adapter protein MyD88 was also increased.
      LPS increased TLR4 mRNA levels, but concomitantly decreased its surface
      expression. IFNgamma counteracted the LPS-induced downregulation of TLR4.
      IFNgamma-primed monocytes showed increased responsiveness to LPS in terms of
      phosphorylation of the interleukin-1 receptor-associated kinase (IRAK;
      immediately downstream of the MyD88 adapter protein), NF-kB DNA binding activity,
      and, accordingly, of cytokine (tumor necrosis factor alpha [TNFalpha] and
      interleukin-12 [IL-12]) production. These results suggest that enhanced TLR4
      expression underlies the long-known priming by IFNgamma of mononuclear phagocytes
      for pathogen recognition and killing as well as its synergism with LPS in
      macrophage activation.

PMID- 11964314
TI  - Caspase-catalyzed cleavage and activation of Mst1 correlates with eosinophil but
      not neutrophil apoptosis.
AB  - We have examined the role of caspase-mediated cleavage of the Ste20-like kinases,
      mammalian sterile 20-like 1 and 2 (Mst1/Mst2), in the mechanism of human
      eosinophil and neutrophil apoptosis. Initial measurements of kinase activity,
      using myelin basic protein (MBP) as a substrate in "in-gel" renaturation assays,
      showed that constitutive eosinophil and neutrophil apoptosis were associated
      temporally with the activation of a 36-kd MBP kinase (p36 MBPK) and a 34-kd MBP
      kinase (p34 MBPK), respectively. A constitutively active 63-kd MBP kinase (p63
      MBPK) was also detected in freshly prepared eosinophils but not neutrophils,
      whose activity was transiently augmented during spontaneous apoptosis.
      Immunoblotting studies demonstrated the expression of Mst1 and Mst2 in
      eosinophils but not neutrophils whereas immunoprecipitation studies identified
      the p63 MBPK activity as being Mst1 and Mst2 and showed that the p36 MBPK
      activity represented the N-terminal catalytic fragment of Mst1. A role for the
      p36 MBPK in eosinophil cell death was supported by studies showing increased
      activation upon exposure to the proapoptotic Fas/CD95-activating antibody, CH-11,
      and attenuation in the presence of the survival-promoting cytokine, interleukin
      5. Furthermore, spontaneous and Fas-induced activation of p36 MBPK was inhibited
      by catalase and the general caspase inhibitor, z-Asp-CH(2)-DCB, at concentrations
      that suppressed eosinophil apoptosis. These studies therefore implicate a role
      for caspase- and H(2)O(2)-mediated cleavage of the Mst1 and the subsequent
      release of the 36-kd catalytic fragment in the mechanism of eosinophil apoptosis.
      In contrast, neutrophil apoptosis occurs independently of Mst1 and Mst2 but
      instead is correlated with the activation of an as-yet-unidentified 34-kd MBPK.

PMID- 11964315
TI  - Erythrocyte survival is promoted by plasma and suppressed by a Bak-derived BH3
      peptide that interacts with membrane-associated Bcl-X(L).
AB  - Erythrocytes have a defined lifespan in vivo, and the signals that maintain their
      survival in circulation or trigger their death are unknown. Here, we investigated
      the control of erythrocyte survival and death in an in vitro culture system where
      erythrocytes survived for 10 days in serum-free medium in the presence or absence
      of bovine serum. Death of the cells in culture was correlated with increased
      exposure of phosphatidylserine and increased levels of intracellular calcium.
      Cell death could be suppressed by supplementing the medium with human plasma or
      serum, resulting in a doubling of the lifespan to 20 days. Freshly isolated
      erythrocytes and cultured erythrocytes were both found to express Bcl-X(L) and,
      to a lesser extent, Bak in membrane protein extracts. Treatment of the cells with
      a Bak-derived BH3 peptide fused to the internalization sequence of the
      antennapedia protein, which has previously been shown to enter cells by diffusion
      and antagonize Bcl-X(L), resulted in substantial cell death in erythrocyte
      cultures. BH3-induced death was accompanied by an immediate increase in
      accumulation of intracellular calcium and could be suppressed by plasma, but not
      by the caspase inhibitor zVAD. A BH3 peptide mutated at amino acid 78 of full
      length Bak required for heterodimerization with Bcl-X(L) had no effect on cell
      viability or calcium levels. We conclude that the BH3 peptide accelerates
      erythrocyte death through antagonization of Bcl-X(L). The data suggest that
      erythrocyte survival is promoted by survival factors in plasma and by membrane
      associated Bcl-X(L.)

PMID- 11964316
TI  - T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell
      transplantation are related to clinical events.
AB  - It is generally believed that homeostatic responses regulate T-cell recovery
      after peripheral stem cell transplantation (PSCT). We studied in detail immune
      recovery in relation to T-cell depletion and clinical events in a group of adult
      patients who underwent PSCT because of hematologic malignancies. Initially,
      significantly increased proportions of dividing naive, memory, and effector
      CD4(+) and CD8(+) T cells were found that readily declined, despite still very
      low numbers of CD4(+) and CD8(+) T cells. After PSCT, increased T-cell division
      rates reflected immune activation because they were associated with episodes of
      infectious disease and graft-versus-host disease (GVHD). T-cell receptor excision
      circles (TRECs) were measured to monitor thymic output of naive T cells. Mean
      TREC content normalized rapidly after PSCT, long before naive T-cell numbers had
      significantly recovered. This is compatible with the continuous thymic production
      of TREC(+) naive T cells and does not reflect homeostatic increases of thymic
      output. TREC content was decreased in patients with GVHD and infectious
      complications, which may be explained by the dilution of TRECs resulting from
      increased proliferation. Combining TREC and Ki67 analysis with repopulation
      kinetics led to the novel insight that recovery of TREC content and increased T
      cell division during immune reconstitution after transplantation are related to
      clinical events rather than to homeostatic adaptation to T-cell depletion.
      (Blood. 2002;99:3449-3453)

PMID- 11964317
TI  - Ex vivo treatment of proliferating human cord blood stem cells with stroma
      derived factor-1 enhances their ability to engraft NOD/SCID mice.
AB  - Ex vivo proliferation of hematopoietic stem cells (HSCs) is important for
      cellular and gene therapy but is limited by the observation that HSCs do not
      engraft as they transit S/G(2)/M. Recently identified candidate inhibitors of
      human HSC cycling are transforming growth factor-beta(1) (TGF-beta(1)) and stroma
      derived factor-1 (SDF-1). To determine the ability of these factors to alter the
      transplantability of human HSCs proliferating in vitro, lin(-) cord blood cells
      were first cultured for 96 hours in serum-free medium containing Flt3 ligand,
      Steel factor, interleukin-3, interleukin-6, and granulocyte colony-stimulating
      factor. These cells were then transferred to medium containing Steel factor and
      thrombopoietin with or without SDF-1 and/or TGF-beta(1) for 48 hours. Exposure to
      SDF-1 but not TGF-beta(1) significantly increased (> 2-fold) the recovery of HSCs
      able to repopulate nonobese diabetic/severe combined immunodeficiency mice. These
      results suggest new strategies for improving the engraftment activity of HSCs
      stimulated to proliferate ex vivo.

PMID- 11964318
TI  - HLA-haploidentical blood progenitor cell transplantation in osteopetrosis.
AB  - Infantile osteopetrosis (OP) carries an extremely poor prognosis unless treated
      early by hematopoietic stem cell transplantation. We explored the use of purified
      blood progenitor cells from HLA-haploidentical parents in 7 patients lacking
      suitable matched donors. Blood progenitor cells were purified by positive
      selection and by additional T-cell depletion using rosette formation. For
      conditioning, patients received busulfan, thiotepa, and either cyclophosphamide
      (5 patients) or fludarabine (2 patients). Stable donor engraftment developed in 6
      of 7 patients. Graft-versus-host disease was not observed. Three of the 7
      patients had no major complications and 4 of 7 had both veno-occlusive disease
      and respiratory failure. Five of 7 patients survive with complete cure of OP at a
      median of 4 years. Patients with OP lacking HLA-matched donors can be
      successfully treated by transplantation of purified blood progenitor cells from
      HLA-haploidentical donors.

PMID- 11964319
TI  - Synergistic induction of apoptosis by simultaneous disruption of the Bcl-2 and
      MEK/MAPK pathways in acute myelogenous leukemia.
AB  - Recent studies suggest that the Bcl-2 and mitogen-activated protein kinase (MAPK)
      pathways together confer an aggressive, apoptosis-resistant phenotype on acute
      myelogenous leukemia (AML) cells. In this study, we analyzed the effects of
      simultaneous inhibition of these 2 pathways. In AML cell lines with
      constitutively activated MAPK, MAPK kinase (MEK) blockade by PD184352 strikingly
      potentiated the apoptosis induced by the small-molecule Bcl-2 inhibitor HA14-1 or
      by Bcl-2 antisense oligonucleotides. Isobologram analysis confirmed the
      synergistic nature of this interaction. Moreover, MEK blockade overcame Bcl-2
      overexpression-mediated resistance to the proapoptotic effects of HA14-1. Most
      importantly, simultaneous exposure to PD184352 significantly (P =.01) potentiated
      HA14-1-mediated inhibition of clonogenic growth in all primary AML samples
      tested. These findings show that the Bcl-2 and MAPK pathways are relevant
      molecular targets in AML and that their concurrent inhibition could be developed
      into a new therapeutic strategy for this disease.

PMID- 11964320
TI  - Transient response to imatinib mesylate (STI571) in a patient with the ETV6-ABL
      t(9;12) translocation.
AB  - We report the transient response of a patient with the ETV6-ABL fusion gene to
      imatinib mesylate (STI571). A 38-year-old man was referred with an erroneous
      diagnosis of Philadelphia-positive chronic myeloid leukemia in blastic
      transformation for treatment with the ABL tyrosine kinase inhibitor, STI571.
      Further investigation indicated that the patient in fact had acute myeloid
      leukemia; no evidence of the Philadelphia translocation or BCR-ABL was found
      using fluorescence in situ hybridization (FISH) or reverse transcription
      polymerase chain reaction. Detailed FISH analysis identified a cryptic t(9;12)
      translocation, and molecular studies confirmed the presence of the ETV6-ABL
      fusion transcript. Because the patient was gravely ill at presentation, treatment
      was commenced immediately with STI571 monotherapy, resulting in considerable
      initial improvement. However within 10 days the patient's condition again
      deteriorated, and he required conventional chemotherapy. This case has
      implications for the design of future studies using STI571 in leukemias involving
      ABL-encoded fusion proteins other than BCR-ABL.

PMID- 11964321
TI  - Significance of the detection of antineutrophil antibodies in children with
      chronic neutropenia.
AB  - We evaluated the clinical characteristics of 41 children with chronic neutropenia
      based on the quantitative analysis of antineutrophil antibodies in serum by flow
      cytometry. According to the strength of antineutrophil antibodies, the patients
      were divided into 3 groups: 12 patients presented negative antibodies, 13
      patients showed weak positive antibodies, and 16 patients showed strong positive
      antibodies. No significant differences were seen in age of diagnosis, severity of
      neutropenia, and infectious complications associated with neutropenia among the 3
      groups. The spontaneous resolution of neutropenia was observed in all patients
      with negative antibodies and in 22 of 29 patients with positive antibodies. The
      age of the recovery of neutropenia and the duration until spontaneous resolution
      of neutropenia were significantly dependent on the antibody strength at the time
      of diagnosis. These results demonstrate that the quantification of antineutrophil
      antibodies at the time of diagnosis may be useful in considering the clinical
      course of chronic neutropenia in childhood.

PMID- 11964322
TI  - High frequency of point mutations clustered within the adenosine triphosphate
      binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph
      positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance.
AB  - Point mutations were found in the adenosine triphosphate (ATP) binding region of
      BCR/ABL in 12 of 18 patients with chronic myeloid leukemia (CML) or Ph-positive
      acute lymphoblastic leukemia (Ph(+) ALL) and imatinib resistance (defined as loss
      of established hematologic response), but they were found in only 1 of 10
      patients with CML with imatinib refractoriness (failure to achieve cytogenetic
      response). In 10 of 10 patients for whom samples were available, the mutation was
      not detected before the initiation of imatinib therapy. Three mutations (T315I,
      Y253H, and F317L present in 3, 1, and 1 patients, respectively) have a predicted
      role in abrogating imatinib binding to BCR/ABL, whereas 3 other mutations (E255K,
      G250E, and M351T, present in 4, 2, and 2 patients, respectively) do not. Thus we
      confirm a high frequency of mutations clustered within the ATP-binding region of
      BCR/ABL in resistant patients. Screening may allow intervention before relapse by
      identifying emerging mutations with defined impacts on imatinib binding. Certain
      mutations may respond to higher doses of imatinib, whereas other mutations may
      mandate switching to another therapeutic strategy.

PMID- 11964323
TI  - Driving and arrhythmias.

PMID- 11964324
TI  - Promoting evidence based practice in maternal care.

PMID- 11964325
TI  - Doctors' knowledge about evidence based medicine terminology.

PMID- 11964326
TI  - Using drugs safely.

PMID- 11964327
TI  - Left and right sided large bowel cancer.

PMID- 11964328
TI  - "Unacceptable" errors found in breast screening service.

PMID- 11964329
TI  - The metatarsal finds stardom at last.

PMID- 11964331
TI  - Single flexible sigmoidoscopy screening could help prevent colorectal cancer.

PMID- 11964332
TI  - Smoker wins 250000 pounds sterling from BAT.

PMID- 11964333
TI  - Labour and Conservatives draw up battle lines on NHS.

PMID- 11964334
TI  - Serious fraud office swoops on drug companies.

PMID- 11964335
TI  - World Medical Association condemns harassment of health workers in West Bank and
      Gaza.

PMID- 11964336
TI  - UK government must stop making heroic promises, report says.

PMID- 11964337
TI  - Comparison of cardiovascular risk between patients with type 2 diabetes and those
      who had had a myocardial infarction: cross sectional and cohort studies.
AB  - OBJECTIVE: To compare risks of cardiovascular outcomes between patients with type
      2 diabetes and patients with established coronary heart disease. DESIGN: Cross
      sectional study and cohort study using routinely collected datasets. SETTING:
      Tayside, Scotland (population 400 000) during 1988-95. SUBJECTS: In the cross
      sectional study, among patients aged 45-64, 1155 with type 2 diabetes were
      compared with 1347 who had had a myocardial infarction in the preceding 8 years.
      In the cohort study 3477 patients of all ages with newly diagnosed type 2
      diabetes were compared with 7414 patients who had just had a myocardial
      infarction. MAIN OUTCOME MEASURES: Risk ratios for death from all causes,
      cardiovascular death, and hospital admission for myocardial infarction were
      calculated by Cox proportional hazards analysis and adjusted for age and sex.
      RESULTS: In the cross sectional study the adjusted risk ratio for death from all
      causes for patients who had myocardial infarction compared with those with
      diabetes was 1.33 (95% confidence interval 1.14 to 1.55) [corrected], and the
      risk ratio for hospital admission for myocardial infarction was 2.27 (1.82 to
      2.83) [corrected]. In the cohort study, patients who had just had a myocardial
      infarction had a higher risk of death from all causes (adjusted risk ratio 1.35
      (1.25 to 1.44)), cardiovascular death (2.93 (2.54 to 3.41)), and hospital
      admission for myocardial infarction (3.10 (2.57 to 3.73)). CONCLUSIONS: Patients
      with type 2 diabetes were at lower risk of cardiovascular outcomes than patients
      with established coronary heart disease.

PMID- 11964338
TI  - Consumer demand for caesarean sections in Brazil: informed decision making,
      patient choice, or social inequality? A population based birth cohort study
      linking ethnographic and epidemiological methods.
AB  - OBJECTIVES: To investigate why some women prefer caesarean sections and how
      decisions to medicalise birthing are influenced by patients, doctors, and the
      sociomedical environment. DESIGN: Population based birth cohort study, using
      ethnographic and epidemiological methods. SETTING: Epidemiological study: women
      living in the urban area of Pelotas, Brazil who gave birth in hospital during the
      study. Ethnographic study: subsample of 80 women selected at random from the
      birth cohort. Nineteen medical staff were interviewed. PARTICIPANTS: 5304 women
      who gave birth in any of the city's hospitals in 1993. MAIN OUTCOME MEASURES:
      Birth by caesarean section or vaginal delivery. RESULTS: In both samples women
      from families with higher incomes and higher levels of education had caesarean
      sections more often than other women. Many lower to middle class women sought
      caesarean sections to avoid what they considered poor quality care and medical
      neglect, resulting from social prejudice. These women used medicalised prenatal
      and birthing health care to increase their chance of acquiring a caesarean
      section, particularly if they had social power in the home. Both social power and
      women's behaviour towards seeking medicalised health care remained significantly
      associated with type of birth after controlling for family income and maternal
      education. CONCLUSIONS: Fear of substandard care is behind many poor women's
      preferences for a caesarean section. Variables pertaining to women's role in the
      process of redefining and negotiating medical risks were much stronger correlates
      of caesarean section rates than income or education. The unequal distribution of
      medical technology has altered concepts of good and normal birthing. Arguments
      supporting interventionist birthing for all on the basis of equal access to
      health care must be reviewed.

PMID- 11964339
TI  - Episiotomy rates in primiparous women in Latin America: hospital based
      descriptive study.

PMID- 11964341
TI  - General practitioners' self ratings of skills in evidence based medicine:
      validation study.

PMID- 11964340
TI  - Effectiveness of teaching general practitioners skills in brief cognitive
      behaviour therapy to treat patients with depression: randomised controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of teaching general practitioners skills
      in brief cognitive behaviour therapy. DESIGN: Parallel group, cluster randomised,
      controlled trial of an educational package on cognitive behaviour therapy.
      SETTING: General practices in north London. PARTICIPANTS: 84 general practitioner
      principals and 272 patients attending their practices who scored above the
      threshold for psychological distress on the hospital anxiety and depression
      scale. INTERVENTION: A training package of four half days on brief cognitive
      behaviour therapy. MAIN OUTCOME MEASURES: Scores on the depression attitude
      questionnaire (general practitioners) and the Beck depression inventory
      (patients). RESULTS: Doctors' knowledge of depression and attitudes towards its
      treatment showed no major difference between intervention and control groups
      after 6 months. The training had no discernible impact on patients' outcomes.
      CONCLUSION: General practitioners may require more training and support than a
      basic educational package on brief cognitive behaviour therapy to acquire skills
      to help patients with depression.

PMID- 11964342
TI  - Factors associated with success in medical school: systematic review of the
      literature.

PMID- 11964343
TI  - Emergency medicine.

PMID- 11964344
TI  - ABC of clinical electrocardiography: Acute myocardial infarction-Part II.

PMID- 11964345
TI  - The rise of regulation in the NHS.

PMID- 11964346
TI  - A tale of two novel transplants not done: the ethics of limb allografts.

PMID- 11964347
TI  - Patients' denial of disease may pose difficulty for achieving informed consent.

PMID- 11964348
TI  - Global alliance on vaccines and immunizations. Save the Children UK had concerns
      about alliance that went further than report did.

PMID- 11964349
TI  - Fifth revision of Declaration of Helsinki. Clause 29 forbids trials from using
      placebos when effective treatment exists.

PMID- 11964350
TI  - Bipolar affective disorder. Suicide statistics were misleading.

PMID- 11964351
TI  - First episode psychosis. Patients must be asked about suicidal ideation and
      substance misuse.

PMID- 11964352
TI  - Preimplantation genetic diagnosis for donor babies carries some harm.

PMID- 11964353
TI  - Rehabilitation services remain important in multiple sclerosis.

PMID- 11964354
TI  - Postoperative chemoradiotherapy helps in gastric adenocarcinoma.

PMID- 11964355
TI  - Endoscopy is useful during percutaneous tracheostomy.

PMID- 11964356
TI  - Income inequality and population health. Better measures of social
      differentiation and hierarchy are needed.

PMID- 11964357
TI  - If only lottery winnings were randomly assigned.

PMID- 11964358
TI  - Surgeons should beware of plans to print individual performance.

PMID- 11964359
TI  - Open letter to the National Blood Service.

PMID- 11964365
TI  - Na(+)-H(+) exchanger inhibition: a new antihypertrophic tool.

PMID- 11964364
TI  - Vascular biology: look what we staggered into.

PMID- 11964366
TI  - Novel AT(1) receptor-independent functions of losartan.

PMID- 11964367
TI  - Prourokinase mutant that induces highly effective clot lysis without interfering
      with hemostasis.
AB  - Prourokinase (proUK) is a zymogenic plasminogen activator that at pharmacological
      doses is prone to nonspecific activation to urokinase. This has handicapped
      therapeutic exploitation of its fibrin-specific physiological properties. To
      attenuate this susceptibility without compromising specific activation of proUK
      on a fibrin clot, a Lys300-->His mutation (M5) was developed. M5 had a lower
      intrinsic activity and, therefore, remained stable in plasma at a 4-fold higher
      concentration than did proUK. M5 had a higher 2-chain activity and induced more
      rapid plasminogen activation and fibrin-specific clot lysis in vitro. Sixteen
      dogs embolized with radiolabeled clots were infused with saline, proUK, tissue
      plasminogen activator, or M5. The lower intrinsic activity allowed a higher
      infusion rate with M5, which induced the most rapid and efficient clot lysis (50%
      clot lysis by approximately 600 microg/kg M5 versus approximately 1200 microg/kg
      proUK). In association with this, M5 caused neither a significant increase in the
      primary bleeding time nor secondary bleeding (total blood loss). By contrast,
      these measurements increased 4-fold and 5-fold, respectively, with proUK and >5
      fold and 8-fold, respectively, with tissue plasminogen activator. Clot lysis by
      M5 and hemostasis were further evaluated in 6 rhesus monkeys. M5 again induced
      rapid clot lysis without a significant increase in the primary bleeding time, and
      secondary bleeding did not occur. In conclusion, a site-directed mutation
      designed to improve the stability of proUK in blood at therapeutic concentrations
      induced superior clot lysis in vitro and in vivo without causing significant
      interference with hemostasis.

PMID- 11964368
TI  - all-trans-Retinoic acid increases nitric oxide synthesis by endothelial cells: a
      role for the induction of dimethylarginine dimethylaminohydrolase.
AB  - all-trans-Retinoic acid (atRA) has important effects on the developing and mature
      cardiovascular system. Nitric oxide (NO) production has been associated with the
      atRA-induced differentiation of neuronal cells, and we hypothesized that NO may
      also mediate certain actions of atRA in the cardiovascular system. We studied the
      effects of atRA on NO production by endothelial cells and determined whether
      regulation of enzymes responsible for metabolism of asymmetric dimethylarginine
      (ADMA) contributed to the effects seen. Murine endothelioma (sEnd.1) cells were
      incubated with or without atRA. Nitrite production was determined using the
      Griess reaction. The expression of NO synthase (NOS) and dimethylarginine
      dimethylaminohydrolase (DDAH) genes was determined by Northern blotting. A
      reporter gene assay was also used to study the effect of atRA on the DDAH II
      promoter. atRA significantly increased nitrite production by sEnd.1 cells despite
      no increase in eNOS expression. atRA also increased DDAH II gene expression and
      promoter activity and reduced the ratio of ADMA to symmetric dimethylarginine
      (SDMA) in culture medium. The DDAH inhibitor 4124W significantly reduced the
      induction of NO synthesis by atRA. The present study demonstrates that atRA
      increases NO synthesis in endothelial cells without increasing eNOS expression.
      atRA also increases the expression of DDAH II, the predominant DDAH isoform in
      endothelial cells. Our data suggests that the induction of NO synthesis by atRA
      may be facilitated by DDAH II. This pathway may help to explain some of the
      effects of atRA on the cardiovascular system.

PMID- 11964370
TI  - Hypoxia causes downregulation of protein and RNA synthesis in noncontracting
      Mammalian cardiomyocytes.
AB  - The aim was to identify energy-consuming processes, other than contraction,
      downregulated during moderate hypoxia ( approximately 5 micromol/L, 0.5% O(2))
      and severe hypoxia (<0.5 micromol/L, <0.05% O(2)) in isolated neonatal
      cardiomyocytes. The metabolic response of cardiomyocytes to moderate and severe
      hypoxia was assessed by measuring rates of energy consumption and energetic
      status of cells maintained under these conditions. We found that the rates of
      energy production were decreased during both forms of hypoxia. Decreased rates of
      energy production under moderate hypoxia were associated with reduced energy
      wastage through a downregulation of proton leak in the mitochondria. Cellular
      protein synthesis and RNA synthesis, major energy-consuming pathways, were
      downregulated only during severe hypoxia, when oxygen concentrations were low
      enough to induce energetic stress (quantitatively defined as being any situation
      in which phosphocreatine concentrations had fallen by > or = 40%). Our results
      suggest that energetic stress is the signal responsible for this downregulation.

PMID- 11964369
TI  - Angiotensin II receptor-independent antiinflammatory and antiaggregatory
      properties of losartan: role of the active metabolite EXP3179.
AB  - Angiotensin II (Ang II) type 1 receptor (AT(1)) antagonists such as losartan
      (LOS) are widely used for the treatment of hypertension and elicit
      antiinflammatory and antiaggregatory in vitro and in patients, although the
      underlying mechanism are unclear. Following computer-based molecule similarity,
      we proposed that on cytochrome-P450 degradation, the LOS metabolite EXP3179 is
      generated, which shows molecule homology to indomethacin, a cyclooxygenase
      inhibitor with antiinflammatory and antiaggregatory properties. Subsequently,
      serum-levels of EXP3179 were determined for 8 hours in patients receiving a
      single oral dose of 100 mg LOS. High-performance liquid chromatography followed
      by liquid chromatography-mass spectrometry (GC-MS) [corrected] from serum samples
      revealed a maximum of 10(-7) mol/L for EXP3179 peaking between 3 to 4 hours. The
      increase in serum-EXP3179 levels was associated with a significant reduction in
      platelet aggregation in vivo (-35+/-4%, P<0.001 versus control). EXP3179
      generation was investigated in a chemical reaction mimicking the liver cytochrome
      P450-dependent LOS-degradation and human endothelial cells were exposed to Ang II
      or lipopolysaccharides (LPS) in the presence of EXP3179 (10(-7) mol/L). LPS- and
      Ang II-induced COX-2 transcription was abolished by EXP3179. Moreover, EXP3179
      significantly reduced Ang II- and LPS-induced formation of prostaglandin F2alpha
      as determined by GC-MS [corrected]. Thus, antiinflammatory properties of LOS are
      mediated via its EXP3179 metabolite by abolishing COX-2 mRNA upregulation and COX
      dependent TXA2 and PGF2alpha generation. Serum levels of EXP3179 are detectable
      in patients in concentrations that exhibit antiinflammatory and antiaggregatory
      properties in vitro.

PMID- 11964371
TI  - Regulation of endothelial matrix metalloproteinase-2 by hypoxia/reoxygenation.
AB  - Among the consequences resulting from the exposure of endothelial cells (ECs) to
      ischemia/reperfusion is angiogenesis, involving degradation of vascular basement
      membrane and extracellular matrix. Matrix metalloproteinase (MMP)-2, a member of
      the MMP family, partakes in this process. MMP-2, secreted as a proenzyme,
      undergoes activation through interaction with membrane type (MT)1-MMP and the
      endogenous tissue inhibitor of MMPs (TIMP)-2. Although hypoxia and reoxygenation
      (H/R) are major constituents of ischemia/reperfusion processes, their direct
      effects on endothelial MMP-2 have been scarcely investigated. This study examined
      the in vitro effects of H/R on human macrovascular ECs (EAhy 926). The level of
      MMP-2 mRNA (Northern blot) and protein (zymography, ELISA) and the mRNA of its
      activator (MT1-MMP) and inhibitor (TIMP-2) were analyzed. Short (6-hour) hypoxia
      inhibited the mRNA expression of MMP-2, MT1-MMP, and TIMP-2, culminating in
      reduced latent and active MMP-2 protein. Prolonged (24-hour) hypoxia further
      suppressed MT1-MMP and TIMP-2 mRNA, whereas it enhanced MMP-2 mRNA and enzyme
      secretion (after 48-hour hypoxia). Reoxygenation did not influence the inhibited
      TIMP-2 but upregulated MMP-2 and MT1-MMP mRNA expression, leading to enhanced
      secretion of active MMP-2 protein. These results demonstrate H/R-mediated
      modulation of EC MMP-2 at both transcriptional and posttranscriptional levels.
      Prolonged hypoxia of ECs appears to enhance MMP-2 production and secretion,
      whereas reoxygenation further increases its level. These H/R-mediated effects on
      MMPs have the potential of enabling EC migration and possible angiogenesis.

PMID- 11964372
TI  - Influence of mitochondrial inhibition on global and local [Ca(2+)](I) in rat tail
      artery.
AB  - Inhibition of oxidative metabolism is often found to decrease contractility of
      systemic vascular smooth muscle, but not to reduce global [Ca(2+)](i). In the
      present study, we probe the hypothesis that it is associated with an altered
      pattern of intracellular Ca(2+) oscillations (waves) influencing force
      development. In the rat tail artery, mitochondrial inhibitors (rotenone,
      antimycin A, and cyanide) reduced alpha(1)-adrenoceptor-stimulated force by 50%
      to 80%, but did not reduce global [Ca(2+)](i). Less relaxation (about 30%) was
      observed after inhibition of myosin phosphatase activity with calyculin A,
      suggesting that part of the metabolic sensitivity involves the regulation of
      myosin 20-kDa light chain phosphorylation, although no decrease in
      phosphorylation was found in freeze-clamped tissue. Confocal imaging revealed
      that the mitochondrial inhibitors increased the frequency but reduced the
      amplitude of asynchronous cellular Ca(2+) waves elicited by alpha(1) stimulation.
      The altered wave pattern, in association with increased basal [Ca(2+)](i),
      accounted for the unchanged global [Ca(2+)](i). Inhibition of glycolytic ATP
      production by arsenate caused similar effects on Ca(2+) waves and global
      [Ca(2+)](i), developing gradually in parallel with decreased contractility.
      Inhibition of wave activity by the InsP(3) receptor antagonist 2-APB correlated
      closely with relaxation. Furthermore, abolition of waves with thapsigargin in the
      presence of verapamil reduced force by about 50%, despite unaltered global
      [Ca(2+)](i), suggesting that contraction may at least partly depend on Ca(2+)
      wave activity. This study therefore indicates that mitochondrial inhibition
      influences Ca(2+) wave activity, possibly due to a close spatial relationship of
      mitochondria and the sarcoplasmic reticulum and that this contributes to
      metabolic vascular relaxation.

PMID- 11964373
TI  - Dynamic modulation of interendothelial gap junctional communication by 11,12
      epoxyeicosatrienoic acid.
AB  - Functional gap junctional communication between vascular cells has been
      implicated in ascending dilatation and the cytochrome P-450 (CYP) inhibitor
      sensitive and NO- and prostacyclin-independent dilatation of many vascular beds.
      Here, we assessed the mechanisms by which the epoxyeicosatrienoic acids (EETs)
      generated by a CYP 2C enzyme control interendothelial gap junctional
      communication. In CYP 2C-expressing porcine coronary endothelial cells,
      bradykinin, which enhances EET formation, elicited a biphasic effect on the
      electrical coupling and transfer of Lucifer yellow between endothelial cells,
      consisting of a transient increase in coupling followed by a sustained
      uncoupling. The initial phase was sensitive to the CYP 2C9 inhibitor
      sulfaphenazole and the protein kinase A (PKA) inhibitors Rp-cAMPS and KT5720 and
      could be mimicked by forskolin and caged cAMP as well as by the PKA activators
      5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole 3',5'-cyclic
      monophosphorothioate sodium salt and Sp-cAMPS. Gap junction uncoupling in
      bradykinin-stimulated porcine coronary endothelial cells was prevented by
      inhibiting the activation of extracellular signal-regulated kinase (ERK)1/2. In
      human endothelial cells, which express little CYP 2C, bradykinin elicited only an
      ERK1/2-mediated inhibition of intercellular communication. The CYP 2C9 product,
      11,12-EET, also exerted a dual effect on the electrical and dye coupling of human
      endothelial cells, which was sensitive to PKA inhibition. These results
      demonstrate that an agonist-activated CYP-dependent pathway as well as 11,12-EET
      can positively regulate interendothelial gap junctional communication, most
      probably via the activation of PKA, an effect that is curtailed by the subsequent
      activation of ERK1/2.

PMID- 11964374
TI  - Myocardial dysfunction with coronary microembolization: signal transduction
      through a sequence of nitric oxide, tumor necrosis factor-alpha, and sphingosine.
AB  - Coronary microembolization results in progressive myocardial dysfunction, with
      causal involvement of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha uses a
      signal transduction involving nitric oxide (NO) and/or sphingosine. Therefore, we
      induced coronary microembolization in anesthetized dogs and studied the role and
      sequence of NO, TNF-alpha, and sphingosine for the evolving contractile
      dysfunction. Four sham-operated dogs served as controls (group 1). Eleven dogs
      received placebo (group 2), 6 dogs received the NO synthase inhibitor N(G)-nitro
      L-arginine methyl ester (L-NAME, group 3), and 6 dogs received the ceramidase
      inhibitor N-oleoylethanolamine (NOE, group 4) before microembolization was
      induced by infusion of 3000 microspheres (42-microm diameter) per milliliter
      inflow into the left circumflex coronary artery. Posterior systolic wall
      thickening (PWT) remained unchanged in group 1 but decreased progressively in
      group 2 from 20.6+/-4.9% (mean+/-SD) at baseline to 4.1+/-3.7% at 8 hours after
      microembolization. Leukocyte count, TNF-alpha, and sphingosine contents were
      increased in the microembolized posterior myocardium. In group 3, PWT remained
      unchanged (20.3+/-2.6% at baseline) with intracoronary administration of L-NAME
      (20.8+/-3.4%) and 17.7+/-2.3% at 8 hours after microembolization; TNF-alpha and
      sphingosine contents were not increased. In group 4, PWT also remained unchanged
      (20.7+/-4.6% at baseline) with intravenous administration of NOE (19.5+/-5.7%)
      and 16.4+/-6.3% at 8 hours after microembolization; TNF-alpha, but not
      sphingosine content, was increased. In all groups, systemic hemodynamics,
      anterior systolic wall thickening, and regional myocardial blood flow remained
      unchanged throughout the protocols. A signal transduction cascade of NO, TNF
      alpha, and sphingosine is causally involved in the coronary microembolization
      induced progressive contractile dysfunction.

PMID- 11964375
TI  - Inhibition of Na(+)-H(+) exchange prevents hypertrophy, fibrosis, and heart
      failure in beta(1)-adrenergic receptor transgenic mice.
AB  - Chronic stimulation of the beta(1)-adrenergic receptor leads to hypertrophy and
      heart failure in beta(1)-adrenergic receptor transgenic mice and contributes to
      disease progression in heart failure patients. The cellular mechanisms underlying
      these detrimental effects are largely unknown. In this study, we have identified
      the cardiac Na(+)-H(+) exchanger (NHE1) as a novel mediator of adrenergically
      induced heart failure. beta(1)-Adrenergic receptor transgenic mice showed
      upregulation of both NHE1 mRNA (+140+/-6%) and protein (+42+/-19%). In order to
      test whether increased NHE1 is causally related to beta(1)-adrenergic-induced
      hypertrophy, fibrosis, and heart failure, beta(1)-adrenergic receptor transgenic
      (TG) and wild-type (WT) littermates were treated with a diet containing 6000 ppm
      of the NHE1 inhibitor cariporide or control chow for 8 months. There was
      significant hypertrophy of cardiac myocytes in beta(1)-adrenergic receptor
      transgenic mice (2.3-fold increase in myocyte cross-sectional area), which was
      virtually absent in cariporide-fed animals. Interstitial fibrosis was prominent
      throughout the left ventricular wall in nontreated beta(1)-adrenergic receptor
      transgenic mice (4.8-fold increase in collagen volume fraction); cariporide
      treatment completely prevented this development of fibrosis. Left ventricular
      catheterization showed that cariporide also prevented the loss of contractile
      function in beta(1)-adrenergic receptor transgenic mice: whereas untreated
      transgenic mice showed a significant decrease in left ventricular contractility
      (5250+/-570 mm Hg/s TG versus 7360+/-540 mm Hg/s WT, dp/dt(max)), this decrease
      was completely prevented by cariporide (8150+/-520 mm Hg/s TG cariporide).
      Inhibition of NHE1 prevented the development of heart failure in beta(1)-receptor
      transgenic mice. We conclude that the cardiac Na(+)-H(+) exchanger 1 is essential
      for the detrimental cardiac effects of chronic beta(1)-receptor stimulation in
      the heart.

PMID- 11964376
TI  - Smooth muscle dysfunction in resistance arteries of the staggerer mouse, a mutant
      of the nuclear receptor RORalpha.
AB  - Retinoic acid receptor-related orphan receptor alpha (RORalpha) is a member of
      the nuclear receptor superfamily. The mouse mutant staggerer (sg/sg) carries a
      deletion within the RORalpha gene. RORalpha plays a major role in cellular
      differentiation during development and growth. In the present study, we found a
      lower mean arterial blood pressure in sg/sg than in +/+ mice (80.1+/-1.2 and
      87.0+/-0.9 mm Hg, respectively; P<0.0002) and a smaller increase in blood
      pressure after in vivo injections of phenylephrine. To elucidate the mechanisms
      responsible for this phenotype, we investigated the vascular reactivity of large
      vessels (aorta and carotid arteries) and small resistance mesenteric arteries in
      response to mechanical forces or vasoactive agents. Arteries from sg/sg and +/+
      mice were studied in vitro in arteriographs. Vascular responses of large vessels
      to all stimuli were similar in both groups. However, we found a markedly altered
      vascular function in mesenteric arteries from sg/sg mice. Flow-induced dilation,
      pressure-induced myogenic tone, responses to endothelium-dependent or 
      independent vasodilators, and responses to vasoconstrictors were significantly
      reduced in sg/sg compared with +/+ mice. We also determined by Western blot
      analysis the expression of smooth muscle (SM)-myosin, calponin, and heavy (h)
      caldesmon, in large and small arteries of sg/sg and +/+ mice, and found a marked
      decrease in the expression of these contractile proteins in mesenteric arteries
      of sg/sg mice. Our findings provide the first evidence that functional RORalpha
      is required for normal contractile phenotype of smooth muscle cells (SMCs) in
      small resistance arteries and suggest that RORalpha might be involved in the
      differentiation of SMCs in mesenteric arteries.

PMID- 11964377
TI  - Arterial ultrastructure influences transport of locally delivered drugs.
AB  - An incomplete understanding of the transport forces and local tissue structures
      that modulate drug distribution has hampered local pharmacotherapies in many
      organ systems. These issues are especially relevant to arteries, where stent
      based delivery allows fine control of locally directed drug release. Local
      delivery produces tremendous drug concentration gradients and although these are
      in part derived from transport forces, differences in deposition from tissue to
      tissue imply that tissue ultrastructure also plays an important role. We measured
      the equilibrium drug uptake and the penetration and diffusivity of dextrans (a
      model hydrophilic drug similar to heparin) and albumin in orthogonal planes in
      arteries explanted from different vascular beds. We found significant variations
      in drug distribution with geometric orientation and arterial connective tissue
      content. Drug diffusivities parallel to the connective tissue sheaths were one to
      two orders of magnitude greater than across these sheaths. This diffusivity
      difference remained relatively constant for drugs up to 70 kDa before decreasing
      for larger drugs. Drugs also distributed better into elastic arteries, especially
      at lower molecular weights, with almost 66% greater transfer into the thoracic
      aorta than into the carotid artery. Arterial drug transport is thus highly
      anisotropic and dependent on arterial tissue content. The role of the local
      composition and geometric organization of arterial tissue in influencing vascular
      pharmacokinetics is likely to become a critical consideration for local vascular
      drug delivery.

PMID- 11964378
TI  - A transcriptional inhibitor targeted by the atypical orphan nuclear receptor SHP.
AB  - SHP (short heterodimer partner, NROB2) is an atypical orphan member of the
      mammalian nuclear receptor family that consists only of a putative ligand-binding
      domain and thus cannot bind DNA. Instead, SHP acts as a transcriptional
      coregulator by inhibiting the activity of various nuclear receptors (downstream
      targets) via occupation of the coactivator-binding surface and active repression.
      However, repression mechanisms have remained elusive and may involve coinhibitory
      factors (upstream targets) distinct from known nuclear receptor corepressors.
      Here, we describe the isolation of mouse E1A-like inhibitor of differentiation 1
      (EID1) as a candidate coinhibitor for SHP. We characterize the interactions
      between SHP and EID1 and identify two repression-defective SHP mutations that
      have lost the ability to bind EID1. We suggest histone acetyltransferases and
      histones as targets for EID1 action and propose that SHP inhibition of
      transcription involves EID1 antagonism of CBP/p300-dependent coactivator
      functions.

PMID- 11964379
TI  - Functional reconstitution of purified metabotropic glutamate receptor expressed
      in the fly eye.
AB  - G-protein-coupled receptors (GPCRs) form one of the largest superfamilies of
      membrane proteins. Obtaining high yields of GPCRs remains one of the major
      factors limiting a detailed understanding of their structure and function.
      Photoreceptor cells (PRCs) contain extensive stacks of specialized membranes
      where high levels of rhodopsins are naturally present, which makes them ideal for
      the overexpression of GPCRs. We have generated transgenic flies expressing a
      number of GPCRs in the PRCs. Drosophila melanogaster metabotropic glutamate
      receptor (DmGluRA) expressed by this novel strategy was purified to homogeneity,
      giving at least 3-fold higher yields than conventional baculovirus expression
      systems due to the higher membrane content of the PRCs. Pure DmGluRA was then
      reconstituted into liposomes of varying composition. Interestingly, glutamate
      binding was strictly dependent on the presence of ergosterol.

PMID- 11964380
TI  - Distinct but overlapping domains of AKAP95 are implicated in chromosome
      condensation and condensin targeting.
AB  - A-kinase (or PKA)-anchoring protein AKAP95 is a zinc-finger protein implicated in
      mitotic chromosome condensation by acting as a targeting molecule for the
      condensin complex. We have identified determinants of chromatin-binding,
      condensin-targeting and chromosome-condensation activities of AKAP95. Binding of
      AKAP95 to chromatin is conferred by residues 387-450 and requires zinc finger
      ZF1. Residues 525-569 are essential for condensation of AKAP95-free chromatin and
      condensin recruitment to chromosomes. Mutation of either zinc finger of AKAP95
      abolishes condensation. However, ZF1 is dispensable for condensin targeting,
      whereas the C-terminal ZF2 is required. AKAP95 interacts with Xenopus XCAP-H
      condensin subunit in vitro and in vivo but not with the human hCAP-D2 subunit.
      The data illustrate the involvement of overlapping, but distinct, domains of
      AKAP95 for condensin recruitment and chromosome condensation and argue for a key
      role of ZF1 in chromosome condensation and ZF2 in condensin targeting. Moreover,
      condensin recruitment to chromatin is not sufficient to promote condensation.

PMID- 11964381
TI  - MyRIP, a novel Rab effector, enables myosin VIIa recruitment to retinal
      melanosomes.
AB  - Defects of the myosin VIIa motor protein cause deafness and retinal anomalies in
      humans and mice. We report on the identification of a novel myosin-VIIa
      interacting protein that we have named MyRIP (myosin-VIIa- and Rab-interacting
      protein), since it also binds to Rab27A in a GTP-dependent manner. In the retinal
      pigment epithelium cells, MyRIP, myosin VIIa and Rab27A are associated with
      melanosomes. In transfected PC12 cells, overexpression of MyRIP was shown to
      interfere with the myosin VIIa tail localization. We propose that a molecular
      complex composed of Rab27A, MyRIP and myosin VIIa bridges retinal melanosomes to
      the actin cytoskeleton and thereby mediates the local trafficking of these
      organelles. The defect of this molecular complex is likely to account for the
      perinuclear mislocalization of the melanosomes observed in the retinal pigment
      epithelium cells of myosinVIIa-defective mice.

PMID- 11964382
TI  - An intron in the YRA1 gene is required to control Yra1 protein expression and
      mRNA export in yeast.
AB  - Yra1p is an essential and conserved mRNA export factor in yeast. Strikingly,
      removal of the intron from YRA1 causes a dominant-negative growth phenotype and a
      concomitant inhibition of mRNA export. However, both defects are neutralized by
      replacement of the intron of YRA1 by a different intron. Significantly, Yra1p is
      overproduced in yeast when expressed from its intronless gene, but Yra1p levels
      are the same as the wild type when expressed from an intron-containing YRA1 gene.
      Thus, an intron in YRA1 controls Yra1p expression and mRNA export.

PMID- 11964383
TI  - The polarized epithelia-specific mu 1B-adaptin complements mu 1A-deficiency in
      fibroblasts.
AB  - The heterotetrameric AP-1A adaptor complex of clathrin-coated vesicles is
      ubiquitously expressed. The mu 1-adaptin subunit of the complex exists as the
      ubiquitous mu 1A and the polarized epithelia-specific mu 1B, which are 80%
      identical. In polarized epithelia, mu 1B is incorporated into the AP-1B complex,
      which is required for basolateral plasma membrane sorting of the low-density
      lipoprotein receptor. Binding of AP-1B to subdomains of the trans-Golgi network
      (TGN) appears to be part of the mechanism by which protein sorting is mediated.
      We expressed mu 1B in mu 1A-deficient fibroblasts to test for mu 1B function in
      non-polarized cells. AP-1B complexes were formed and bound to the TGN and to
      endosomes. Moreover, AP-1B restored the AP-1A-dependent sorting of mannose 6
      phosphate receptors between endosomes and the TGN. This demonstrates that mu 1A
      and mu 1B do have overlapping sorting functions and indicates that AP-1A and AP
      1B mediate protein sorting along parallel pathways between the TGN and endosomes
      in polarized epithelia.

PMID- 11964384
TI  - APC/Fizzy-Related targets Aurora-A kinase for proteolysis.
AB  - Aurora-A kinase is a mitotic spindle-pole-associated protein that has been
      implicated in duplication and separation of centrosomes and in spindle assembly.
      The proper timing and amplitude of Aurora-A expression seems to be important, as
      elevated levels of this protein have been associated with centrosome
      abnormalities and aneuploidy in mammalian cells. We show that Aurora-A increases
      at the G2-M transistion and disappears completely at G1 in XL2 cells. Using
      Xenopus oocyte extracts, we demonstrate that degradation of Aurora-A is mediated
      by the anaphase-promoting complex (APC) and is regulated by Fizzy-Related but not
      by Fizzy. Degradation of Aurora-A depends on a D-Box, but not on its KEN-Box
      motif, as mutation of its C-terminal D-Box sequence induces stabilization of the
      protein. Accordingly, addition into the extracts of a cyclin B-type D-Box-motif
      containing peptide completely suppresses its degradation. Furthermore, APC/Fizzy
      Related ubiquitylates the wild type but not a D-Box mutant form of Aurora-A in
      vitro. Consistent with these data, ectopic expression of Fizzy-Related in Xenopus
      oocytes induces complete degradation of endogenous Aurora-A. Aurora-A is thus the
      first protein, at least in our assay system, that undergoes a D-Box-dependent
      degradation mediated by APC/Fizzy-Related but not by APC/Fizzy.

PMID- 11964385
TI  - Spontaneous insertion and partitioning of alkaline phosphatase into model lipid
      rafts.
AB  - Several cell surface eukaryotic proteins have a glycosylphosphatidylinositol
      (GPI) modification at the C-terminal end that serves as an anchor to the plasma
      membrane and could be responsible for the presence of GPI proteins in rafts, a
      type of functionally important membrane microdomain enriched in sphingolipids and
      cholesterol. In order to understand better how GPI proteins partition into rafts,
      the insertion of the GPI-anchored alkaline phosphatase (AP) was studied in real
      time using atomic force microscopy. Supported phospholipid bilayers made of a
      mixture of sphingomyelin-dioleoylphosphatidylcholine containing cholesterol
      (Chl+) or not (Chl-) were used to mimic the fluid-ordered lipid phase separation
      in biological membranes. Spontaneous insertion of AP through its GPI anchor was
      observed inside both Chl+ and Chl- lipid ordered domains, but AP insertion was
      markedly increased by the presence of cholesterol.

PMID- 11964386
TI  - Efficient biallelic mutagenesis with Cre/loxP-mediated inter-chromosomal
      recombination.
AB  - The isolation of mutant cells with phenotypes caused by random mutagenesis has
      been hampered in mammalian cells because there are two alleles per gene and the
      disruption of both alleles is extremely rare. We describe a method for the
      efficient biallelic mutagenesis in embryonic stem cells. loxP sites were
      introduced near the centromeric regions of a pair of chromosome 1s. A mutant neo
      gene was inserted at the distal part of one of the loxP sites so that biallelic
      mutants would be selected by high-dose G418. Expression of Cre induced the
      recombination between homologous chromosomes and led to an elevation in the
      number of biallelic mutants. This system will facilitate phenotype-driven gene
      function study in the mammalian system.

PMID- 11964387
TI  - Identification of genes by hybrid ribozymes that couple cleavage activity with
      the unwinding activity of an endogenous RNA helicase.
AB  - Novel ribozymes that couple the cleavage activity of hammerhead ribozymes with
      the unwinding activity of RNA helicase eIF4AI were constructed. This leads to
      extremely efficient cleavage of the target mRNA, regardless of the secondary
      structure of the RNA, and eliminates one of the major problems: many target sites
      on the RNA were previously inaccessible to cleavage due to secondary and/or
      tertiary structure formation. Moreover, libraries of hybrid ribozymes with
      randomized binding arms were introduced into cells. This procedure made it
      possible to readily identify the relevant genes associated with phenotype.
      Specifically, four genes known to be in the Fas-mediated apoptosis pathway were
      identified along with additional genes. This application of a randomized library
      of hybrid ribozymes represents a simple, powerful method for the identification
      of genes associated with specific phenotypes in the post-genome era.

PMID- 11964388
TI  - Regulation of mitochondrial D-loops by transcription factor A and single-stranded
      DNA-binding protein.
AB  - During replication, mitochondrial DNA (mtDNA) takes on a triple-stranded
      structure called a D-loop. Although their physiological roles are not understood,
      D-loops are implicated in replication and transcription of mtDNA. Little is known
      about the turnover of D-loops. We investigated the effects of mitochondrial
      transcription factor A (TFAM) and single-stranded DNA-binding protein (mtSSB) on
      D-loops. In human HeLa cells, TFAM and mtSSB are, respectively, 1700- and 3000
      fold more abundant than mtDNA. This level of TFAM is two orders of magnitude
      higher than reported previously and is sufficient to wrap human mtDNA entirely.
      TFAM resolves D-loops in vitro if added in similar stoichiometries. mtSSB
      inhibits the resolution of mtDNA by TFAM but enhances resolution by RecG, a
      junction-specific helicase from Escherichia coli. Hence, mtSSB functions in both
      stabilization and resolution. We propose that TFAM and mtSSB are cooperatively
      involved in stabilizing D-loops and in the maintenance of mtDNA.

PMID- 11964389
TI  - hINADl/PATJ, a homolog of discs lost, interacts with crumbs and localizes to
      tight junctions in human epithelial cells.
AB  - dCrumbs is an apical organizer crucial for the maintenance of epithelial polarity
      in Drosophila (1). It is known that dCrumbs interacts with Discs lost (Dlt), a
      protein with four PDZ (PSD95/Discs Large/ZO-1) domains (2), and Stardust (Sdt), a
      protein of the MAGUK (membrane-associated guanylate kinase) family (3, 4). We
      have searched for potential homologs of Dlt in human epithelial cells and
      characterized one of them in intestinal epithelial cells. Human INAD-like
      (hINADl) contains 8 PDZ domains, is concentrated in tight junctions, and is also
      found at the apical plasma membrane. Overexpression of hINADl disrupted the tight
      junctions localization of ZO-1 and 3. We also identified a partial cDNA coding
      the transmembrane and cytoplasmic domains of a new human crumbs (CRB3) expressed
      in Caco-2 cells. This CRB3 was able to interact through its C-terminal end with
      the N-terminal domain of hINADl. Taken together, the data indicate that hINADl is
      likely to represent a Dlt homolog in mammalian epithelial cells and might be
      involved in regulating the integrity of tight junctions. We thus propose to
      rename hINADl PATJ for protein associated to tight junctions.

PMID- 11964390
TI  - Flipping duplex DNA inside out: a double base-flipping reaction mechanism by
      Escherichia coli MutY adenine glycosylase.
AB  - The Escherichia coli MutY adenine glycosylase plays a critical role in repairing
      mismatches in DNA between adenine and the oxidatively damaged guanine base 8
      oxoguanine. Crystallographic studies of the catalytic core domain of MutY show
      that the scissile adenine is extruded from the DNA helix to be bound in the
      active site of the enzyme (Guan, Y., Manuel, R. C., Arvai, A. S., Parikh, S. S.,
      Mol, C. D., Miller, J. H., Lloyd, S., and Tainer, J. A. (1998) Nat. Struct. Biol.
      5, 1058-1064). However, the structural and mechanistic bases for the recognition
      of the 8-oxoguanine remain poorly understood. In experiments using a single
      stranded 8-bromoguanine-containing synthetic oligodeoxyribonucleotide alone and
      in a duplex construct mismatched to an adenine, we observed UV cross-linking
      between MutY and the 8-bromoguanine probe. We further observed enhanced cross
      linking in the single strand experiments, suggesting that neither the duplex
      context nor the mismatch with adenine is required for recognition of the 8
      oxoguanine moiety. Stopped-flow fluorescence studies using 2-aminopurine
      containing oligodeoxyribonucleotides further revealed the sequential extrusion of
      the 8-oxoguanine at 108 s(-1) followed by the adenine at 16 s(-1). A protein
      isomerization step following base flipping at 1.9 s(-1) was also observed and is
      postulated to provide additional stabilization of the extruded adenine thereby
      facilitating its capture by the active site for excision.

PMID- 11964391
TI  - Manganese(II) induces apoptotic cell death in NIH3T3 cells via a caspase-12
      dependent pathway.
AB  - Under physiological conditions, manganese(II) exhibits catalase-like activity.
      However, at elevated concentrations, it induces apoptosis via a non-mitochondria
      mediated mechanism (Oubrahim, H., Stadtman, E. R., and Chock, P. B. (2001) Proc.
      Natl. Acad. Sci. U. S. A. 98, 9505-9510). In this study, we show that the Mn(II)
      induced apoptosis, as monitored by caspase-3-like activity, in NIH3T3 cells was
      inhibited by calpain inhibitors I and II or the p38 MAP kinase inhibitor,
      SB202190. The control experiments showed that each of these inhibitors in the
      concentration ranges used exerted no effect on activated caspase-3-like activity.
      Furthermore, caspase-12 was cleaved in Mn(II)-treated cells, suggesting that the
      Mn(II)-induced apoptosis is mediated by caspase-12. This notion is confirmed by
      the observations that pretreatment of NIH3T3 cells with either caspase-12
      antisense RNA or dsRNA corresponding to the full-length caspase-12 led to a
      dramatic decrease in caspase-3-like activity induced by Mn(II). The precise
      mechanism by which Mn(II) induced the apoptosis is not clear. Nevertheless,
      Mn(II), in part, exerts its effect via its ability to replace Ca(II) in the
      activation of m-calpain, which in turn activates caspase-12 and degrades Bcl-xL.
      In addition, the dsRNA(i) method serves as an effective technique for knocking
      out caspase-12 in NIH3T3 cells without causing apoptosis.

PMID- 11964393
TI  - Single-cell fluorescence resonance energy transfer analysis demonstrates that
      caspase activation during apoptosis is a rapid process. Role of caspase-3.
AB  - Activation of effector caspases is considered to be the final step in many
      apoptosis pathways. We transfected HeLa cells with a recombinant caspase
      substrate composed of cyan and yellow fluorescent protein and a linker peptide
      containing the caspase cleavage sequence DEVD, and we examined the cleavage
      kinetics at the single-cell level by fluorescence resonance energy transfer
      (FRET) analysis. Caspase activation in response to tumor necrosis factor-alpha,
      staurosporine, or etoposide resulted in cleavage of the linker peptide and
      subsequent disruption of the FRET signal. The time to caspase activation varied
      among individual cells, depending on the type of treatment and concentration
      used. However, once initiated, disruption of the FRET signal was always rapid
      (<or=15 min) and largely independent of these parameters. In contrast, FRET probe
      cleavage was significantly slower in the caspase-3-deficient MCF-7 cells,
      particularly at low concentrations of the pro-apoptotic agents. Under these
      conditions, MCF-7 cells required up to 90 min for the FRET probe cleavage,
      whereas MCF-7/Casp-3 cells displayed rapid cleavage kinetics. Interestingly, we
      could still observe comparable cell death rates in MCF-7 and MCF-7/Casp-3 cells.
      Our results suggest that caspase activation during apoptosis occurs in an "all or
      nothing" fashion. Caspase-3 is required for rapid cleavage kinetics when the
      onset of apoptosis is slow, suggesting the existence of caspase-3-dependent
      feedback loops.

PMID- 11964392
TI  - Cooperative, ATP-dependent association of the nucleotide binding cassettes during
      the catalytic cycle of ATP-binding cassette transporters.
AB  - ATP-binding cassette (ABC) transporters harvest the energy present in cellular
      ATP to drive the translocation of a structurally diverse set of solutes across
      the membrane barriers of eubacteria, archaebacteria, and eukaryotes. The
      positively cooperative ATPase activity (Hill coefficient, 1.7) of a model soluble
      cassette of known structure, MJ0796, from Methanococcus jannaschii indicates that
      at least two binding sites participate in the catalytic reaction. Mutation of the
      catalytic base in MJ0796, E171Q, produced a cassette that can bind but not
      efficiently hydrolyze ATP. The equivalent mutation (E179Q) in a homologous
      cassette, MJ1267, had an identical effect. Both mutant cassettes formed dimers in
      the presence of ATP but not ADP, indicating that the energy of ATP binding is
      first coupled to the transport cycle through a domain association reaction. The
      non-hydrolyzable nucleotides adenosine 5'-(beta,gamma-imino)triphosphate and
      adenosine 5'-3-O-(thio)triphosphate were poor analogues of ATP in terms of their
      ability to promote dimerization. Moreover, inclusion of MgCl2, substitution of
      KCl for NaCl, or alterations in the polarity of the side chain at the catalytic
      base all weakened the ATP-dependent dimer, suggesting that electrostatic
      interactions are critical for the association reaction. Thus, upon hydrolysis of
      bound ATP and the release of product, both electrostatic and conformational
      changes drive the cassettes apart, providing a second opportunity to couple free
      energy changes to the transport reaction.

PMID- 11964394
TI  - Identification of ribosome-binding protein p34 as an intracellular protein that
      binds acidic fibroblast growth factor.
AB  - With the aim of identifying new intracellular binding partners for acidic
      fibroblast growth factor (aFGF), proteins from U2OS human osteosarcoma cells were
      adsorbed to immobilized aFGF. One of the adsorbed proteins is a member of the
      leucine-rich repeat protein family termed ribosome-binding protein p34 (p34).
      This protein has previously been localized to endoplasmic reticulum membranes and
      is thought to span the membrane with the N terminus on the cytosolic side.
      Confocal microscopy of cells transfected with Myc-p34 confirmed the endoplasmic
      reticulum localization, and Northern blotting determined p34 mRNA to be present
      in a multitude of different tissues. Cross-linking experiments indicated that the
      protein is present in the cell as a dimer. In vitro translated p34 was found to
      interact with maltose-binding protein-aFGF through its cytosolic coiled-coil
      domain. The interaction between aFGF and p34 was further characterized by surface
      plasmon resonance, giving a K(D) of 1.4 +/- 0.3 microm. Even though p34
      interacted with mitogenic aFGF, it bound poorly to the non-mitogenic aFGF(K132E)
      mutant, indicating a possible involvement of p34 in intracellular signaling by
      aFGF.

PMID- 11964395
TI  - Phosphoenolpyruvate carboxykinase overexpression selectively attenuates insulin
      signaling and hepatic insulin sensitivity in transgenic mice.
AB  - The ability of insulin to suppress gluconeogenesis in type II diabetes mellitus
      is impaired; however, the cellular mechanisms for this insulin resistance remain
      poorly understood. To address this question, we generated transgenic (TG) mice
      overexpressing the phosphoenolpyruvate carboxykinase (PEPCK) gene under control
      of its own promoter. TG mice had increased basal hepatic glucose production
      (HGP), but normal levels of plasma free fatty acids (FFAs) and whole-body glucose
      disposal during a hyperinsulinemic-euglycemic clamp compared with wild-type
      controls. The steady-state levels of PEPCK and glucose-6-phosphatase mRNAs were
      elevated in livers of TG mice and were resistant to down-regulation by insulin.
      Conversely, GLUT2 and glucokinase mRNA levels were appropriately regulated by
      insulin, suggesting that insulin resistance is selective to gluconeogenic gene
      expression. Insulin-stimulated phosphorylation of the insulin receptor, insulin
      receptor substrate (IRS)-1, and associated phosphatidylinositol 3-kinase were
      normal in TG mice, whereas IRS-2 protein and phosphorylation were down-regulated
      compared with control mice. These results establish that a modest (2-fold)
      increase in PEPCK gene expression in vivo is sufficient to increase HGP without
      affecting FFA concentrations. Furthermore, these results demonstrate that PEPCK
      overexpression results in a metabolic pattern that increases glucose-6
      phosphatase mRNA and results in a selective decrease in IRS-2 protein, decreased
      phosphatidylinositol 3-kinase activity, and reduced ability of insulin to
      suppress gluconeogenic gene expression. However, acute suppression of HGP and
      glycolytic gene expression remained intact, suggesting that FFA and/or IRS-1
      signaling, in addition to reduced IRS-2, plays an important role in downstream
      insulin signal transduction pathways involved in control of gluconeogenesis and
      progression to type II diabetes mellitus.

PMID- 11964396
TI  - Suppression of death receptor signaling in cerebellar Purkinje neurons protects
      neighboring granule neurons from apoptosis via an insulin-like growth factor I
      dependent mechanism.
AB  - Neuronal apoptosis contributes to the progression of neurodegenerative disease.
      Primary cerebellar granule neurons are an established in vitro model for
      investigating neuronal death. After removal of serum and depolarizing potassium,
      granule neurons undergo apoptosis via a mechanism that requires intrinsic
      (mitochondrial) death signals; however, the role of extrinsic (death receptor
      mediated) signals is presently unclear. Here, we investigate involvement of death
      receptor signaling in granule neuron apoptosis by expressing adenoviral, AU1
      tagged, dominant-negative Fas-associated death domain (Ad-AU1-deltaFADD). Ad-AU1
      deltaFADD decreased apoptosis of granule neurons from 65 +/- 5 to 27 +/- 2% (n =
      7, p < 0.01). Unexpectedly, immunocytochemical staining for AU1 revealed that <5%
      of granule neurons expressed deltaFADD. In contrast, deltaFADD was expressed in
      >95% of calbindin-positive Purkinje neurons ( approximately 2% of the cerebellar
      culture). Granule neurons in proximity to deltaFADD-expressing Purkinje cells
      demonstrated markedly increased survival. Both granule and Purkinje neurons
      expressed insulin-like growth factor-I (IGF-I) receptors, and deltaFADD-mediated
      survival of granule neurons was inhibited by an IGF-I receptor blocking antibody.
      These results demonstrate that the selective suppression of death receptor
      signaling in Purkinje neurons is sufficient to rescue neighboring granule neurons
      that depend on Purkinje cell-derived IGF-I. Thus, the extrinsic death pathway has
      a profound but indirect effect on the survival of cerebellar granule neurons.

PMID- 11964397
TI  - RACK1 is an insulin-like growth factor 1 (IGF-1) receptor-interacting protein
      that can regulate IGF-1-mediated Akt activation and protection from cell death.
AB  - The insulin receptor and insulin-like growth factor 1 receptor (IGF-1R),
      activated by their ligands, control metabolism, cell survival, and proliferation.
      Although the signaling pathways activated by these receptors are well
      characterized, regulation of their activity is poorly understood. To identify
      regulatory proteins we undertook a two-hybrid screen using the IGF-1R beta-chain
      as bait. This screen identified Receptor for Activated C Kinases (RACK1) as an
      IGF-1R-interacting protein. RACK1 also interacted with the IGF-1R in fibroblasts
      and MCF-7 cells and with endogenous insulin receptor in COS cells. Interaction
      with the IGF-1R did not require tyrosine kinase activity or receptor
      autophosphorylation but did require serine 1248 in the C terminus. Overexpression
      of RACK1 in either R+ fibroblasts or MCF-7 cells inhibited IGF-1-induced
      phosphorylation of Akt, whereas it enhanced phosphorylation of Erks and Jnks.
      Src, the p85 subunit of phosphatidylinositol 3-kinase, and SHP-2 were all
      associated with RACK1 in these cells. Interestingly, the proliferation of MCF-7
      cells was enhanced by overexpression of RACK1, whereas IGF-1-mediated protection
      from etoposide killing was greatly reduced. Altogether the data indicate that
      RACK1 is an IGF-1R-interacting protein that can modulate receptor signaling and
      suggest that RACK1 has a particular role in regulating Akt activation and cell
      survival.

PMID- 11964398
TI  - Cooperative interaction of Xvent-2 and GATA-2 in the activation of the ventral
      homeobox gene Xvent-1B.
AB  - The Xvent family of homeobox transcription factors is essential for the
      establishment of the dorsal-ventral body axis during Xenopus embryogenesis. In
      contrast to Xvent-2B and other members of the Xvent-2 subfamily, Xvent-1B is not
      a direct response gene of bone morphogenetic protein-4 signaling. Xvent-1B is
      activated by Xvent-2, but CHX experiments revealed the requirement of additional
      factors. In this study, we report on the cooperative effect of Xvent-2 and the
      zinc finger transcription factor GATA-2 on the promoter of the Xvent-1B gene. We
      show that GATA-2 is a direct target gene of bone morphogenetic protein-4 and that
      GATA-2 interacts with Xvent-2 to activate transcription of Xvent-1B. Both
      transcription factors bind to distinct elements within the Xvent-1B promoter, and
      GATA-2 physically interacts with the C-terminal domain of Xvent-2.
      Promoter/reporter studies in Xenopus embryos revealed that full activation of
      Xvent-1B requires both Xvent-2 and GATA-2. Moreover, the two factors are
      sufficient to direct transcription of Xvent-1B in the presence of CHX at the
      ventral side of the embryo. The failure of both factors to activate Xvent-1B on
      the dorsal side suggests the existence of a dorsal inhibitor. This inhibitor is
      likely a component of the dorsal Wnt signaling pathway because nuclear
      translocation of beta-catenin before midblastula transition results in a
      suppression of Xvent-1B transcription.

PMID- 11964399
TI  - Megalin functions as an endocytic sonic hedgehog receptor.
AB  - Embryos deficient in the morphogen Sonic hedgehog (Shh) or the endocytic receptor
      megalin exhibit common neurodevelopmental abnormalities. Therefore, we have
      investigated the possibility that a functional relationship exists between the
      two proteins. During embryonic development, megalin was found to be expressed
      along the apical surfaces of neuroepithelial cells and was coexpressed with Shh
      in the ventral floor plate of the neural tube. Using enzyme-linked immunosorbent
      assay, homologous ligand displacement, and surface plasmon resonance techniques,
      it was found that the amino-terminal fragment of Shh (N-Shh) bound to megalin
      with high affinity. Megalin-expressing cells internalized N-Shh through a
      mechanism that was inhibited by antagonists of megalin, viz. anti-receptor
      associated protein and anti-megalin antibodies. Heparin also inhibited N-Shh
      endocytosis, implicating proteoglycans in the internalization process, as has
      been described for other megalin ligands. Use of chloroquine to inhibit lysosomal
      proteinase activity showed that N-Shh endocytosed via megalin was not efficiently
      targeted to the lysosomes for degradation. The ability of megalin-internalized N
      Shh to bypass lysosomes may relate to the finding that the interaction between N
      Shh and megalin was resistant to dissociation with low pH. Together, these
      findings show that megalin is an efficient endocytic receptor for N-Shh.
      Furthermore, they implicate megalin as a new regulatory component of the Shh
      signaling pathway.

PMID- 11964400
TI  - F1-ATPase, the C-terminal end of subunit gamma is not required for ATP hydrolysis
      driven rotation.
AB  - ATP hydrolysis by the isolated F(1)-ATPase drives the rotation of the central
      shaft, subunit gamma, which is located within a hexagon formed by subunits
      (alphabeta)(3). The C-terminal end of gamma forms an alpha-helix which properly
      fits into the "hydrophobic bearing" provided by loops of subunits alpha and beta.
      This "bearing" is expected to be essential for the rotary function. We checked
      the importance of this contact region by successive C-terminal deletions of 3, 6,
      9, 12, 15, and 18 amino acid residues (Escherichia coli F(1)-ATPase). The ATP
      hydrolysis activity of a load-free ensemble of F(1) with 12 residues deleted
      decreased to 24% of the control. EF(1) with deletions of 15 or 18 residues was
      inactive, probably because it failed to assemble. The average torque generated by
      a single molecule of EF(1) when loaded by a fluorescent actin filament was,
      however, unaffected by deletions of up to 12 residues, as was their rotational
      behavior (all samples rotated during 60 +/- 19% of the observation time).
      Activation energy analysis with the ensemble revealed a moderate decrease from 54
      kJ/mol for EF(1) (full-length gamma) to 34 kJ/mol for EF(1)(gamma-12). These
      observations imply that the intactness of the C terminus of subunit gamma
      provides structural stability and/or routing during assembly of the enzyme, but
      that it is not required for the rotary action under load, proper.

PMID- 11964401
TI  - Peptides identify the critical hotspots involved in the biological activation of
      the insulin receptor.
AB  - We used phage display to generate surrogate peptides that define the hotspots
      involved in protein-protein interaction between insulin and the insulin receptor.
      All of the peptides competed for insulin binding and had affinity constants in
      the high nanomolar to low micromolar range. Based on competition studies,
      peptides were grouped into non-overlapping Sites 1, 2, or 3. Some Site 1 peptides
      were able to activate the tyrosine kinase activity of the insulin receptor and
      act as agonists in the insulin-dependent fat cell assay, suggesting that Site 1
      marks the hotspot involved in insulin-induced activation of the insulin receptor.
      On the other hand, Site 2 and 3 peptides were found to act as antagonists in the
      phosphorylation and fat cell assays. These data show that a peptide display can
      be used to define the molecular architecture of a receptor and to identify the
      critical regions required for biological activity in a site-directed manner.

PMID- 11964402
TI  - The X-ray structure of ferric Escherichia coli flavohemoglobin reveals an
      unexpected geometry of the distal heme pocket.
AB  - The x-ray structure of ferric unliganded lipid-free Escherichia coli
      flavohemoglobin has been solved to a resolution of 2.2 A and refined to an R
      factor of 19%. The overall fold is similar to that of ferrous lipid-bound
      Alcaligenes eutrophus flavohemoglobin with the notable exception of the E helix
      positioning within the globin domain and a rotation of the NAD binding module
      with respect to the FAD-binding domain accompanied by a substantial rearrangement
      of the C-terminal region. An inspection of the heme environment in E. coli
      flavohemoglobin reveals an unexpected architecture of the distal pocket. In fact,
      the distal site is occupied by the isopropyl side chain Leu-E11 that shields the
      heme iron from the residues in the topological positions predicted to interact
      with heme iron-bound ligands, namely Tyr-B10 and Gln-E7, and stabilizes a
      pentacoordinate ferric iron species. Ligand binding properties are consistent
      with the presence of a pentacoordinate species in solution as indicated by a very
      fast second order combination rates with imidazole and azide. Surprisingly,
      imidazole, cyanide, and azide binding profiles at equilibrium are not accounted
      for by a single site titration curve but are biphasic and strongly suggest the
      presence of two distinct conformers within the liganded species.

PMID- 11964403
TI  - CheA kinase and chemoreceptor interaction surfaces on CheW.
AB  - Chemotactic responses of Escherichia coli to aspartic acid are initiated by a
      ternary protein complex composed of Tar (chemoreceptor), CheA (kinase), and CheW
      (a coupling protein that binds to both Tar and CheA and links their activities).
      We used a genetic selection based on the yeast two-hybrid assay to identify nine
      cheW point mutations that specifically disrupted CheW interaction with CheA but
      not with Tar. We sequenced these single point mutants and purified four of the
      mutant CheW proteins for detailed biochemical characterizations that demonstrated
      the weakened affinity of the mutant CheW proteins for CheA, but not for Tar. In
      the three-dimensional structure of CheW, the positions affected by these
      mutations cluster on one face of the protein, defining a potential binding
      interface for interaction of CheW with CheA. We used a similar two-hybrid
      approach to identify four mutation sites that disrupted CheW binding to Tar.
      Mapping of these "Tar-sensitive" mutation sites and those from previous
      suppressor analysis onto the structure of CheW defined an extended surface on a
      face of the protein that is adjacent to the CheA-binding surface and that may
      serve as an interface for CheW binding to Tar.

PMID- 11964404
TI  - Inwardly rectifying K+ (Kir) channels in Drosophila. A crucial role of cellular
      milieu factors Kir channel function.
AB  - Three cDNAs encoding inwardly rectifying potassium (Kir) channels were isolated
      from Drosophila melanogaster. The protein sequences of Drosophila KirI (dKirI)
      and dKirII are moderately (<44%) and dKirIII sequence is weakly (<27%) identical
      to human Kir channel subunits. During fly development, five dKir channel
      transcripts derived from three genes are differentially expressed. Whole mount in
      situ hybridizations revealed dKirI transcripts absent from embryos, but dKirII
      and dKirIII are expressed in the embryonic hind gut and in Malpighian tubules,
      respectively, thus covering the entire osmoregulatory system of the developing
      fly. In the head of adult flies, predominantly dKirII transcripts were detected.
      When expressed in Xenopus oocytes, dKir channel activity was only observed after
      amino acid substitutions in their cytosolic tails (e.g. exchange of a unique
      valine in the NH(2) terminus). In contrast, heterologous expression of wild type
      dKirI and dKirII in Drosophila S2 cells readily evoked typical inwardly
      rectifying K(+) currents, which were weakly sensitive to Ba(2+). Thus, the
      specific milieu of insect cells provides a crucial cellular environment for
      proper function of dKir channels.

PMID- 11964405
TI  - Reduced body weight and increased postimplantation fetal death in tyrosylprotein
      sulfotransferase-1-deficient mice.
AB  - Tyrosine sulfation is mediated by one of two Golgi isoenzymes, called
      tyrosylprotein sulfotransferases (TPST-1 and TPST-2). A relatively small number
      of proteins are known to undergo tyrosine sulfation, including certain adhesion
      molecules, G-protein-coupled receptors, coagulation factors, serpins,
      extracellular matrix proteins, and hormones. As one approach to explore the role
      of these enzymes in vivo and how they might interact in biological systems, we
      have generated TPST-1-deficient mice by targeted disruption of the Tpst1 gene.
      Tpst1(+/-) mice appear normal and, when interbred, yield litters of normal size
      with a Mendelian genetic distribution and an equal sex distribution. Tpst1(-/-)
      mice appear healthy but have approximately 5% lower average body weight than
      Tpst1(+/+) controls. In addition, we show that although fertility of Tpst1(-/-)
      males and females per se is normal, Tpst1(-/-) females have significantly smaller
      litters because of fetal death between 8.5 and 15.5 days postcoitum. These
      findings suggest that there are proteins involved in regulation of body weight
      and reproductive physiology, which require tyrosine sulfation for optimal
      function that are yet to be described. Our findings also strongly support the
      conclusion that TPST-1 and TPST-2 have distinct biological roles that may reflect
      differences in their macromolecular substrate specificity.

PMID- 11964406
TI  - Endoplasmic reticulum-bound ribosomes reside in stable association with the
      translocon following termination of protein synthesis.
AB  - In current views, translation-coupled ribosome binding to the endoplasmic
      reticulum (ER) membrane is transient, with association occurring via the signal
      recognition particle pathway and dissociation occurring upon the termination of
      protein synthesis. Recent studies indicate, however, that ribosomal subunits
      remain membrane-bound following the termination of protein synthesis. To define
      the mechanism of post-termination ribosome association with the ER membrane,
      membrane-bound ribosomes were detergent-solubilized from tissue culture cells at
      different stages of the protein synthesis cycle, and the composition of the
      ribosome-associated membrane protein fraction was determined. We report that
      ribosomes reside in stable association with the Sec61alpha-translocon following
      the termination stage of protein synthesis. Additionally, in vitro experiments
      revealed that solubilized, gradient-purified ribosome-translocon complexes were
      able to initiate the translation of secretory and cytosolic proteins and were
      functional in assays of signal sequence recognition. Using this experimental
      system, synthesis of signal sequence-bearing polypeptides yielded a tight
      ribosome-translocon junction; synthesis of nascent polypeptides lacking a signal
      sequence resulted in a disruption of this junction. On the basis of these data,
      we propose that in situ, ribosomes reside in association with the translocon
      throughout the cycle of protein synthesis, with membrane release occurring upon
      translation of proteins lacking topogenic signals.

PMID- 11964407
TI  - Transforming growth factor-beta stimulates parathyroid hormone-related protein
      and osteolytic metastases via Smad and mitogen-activated protein kinase signaling
      pathways.
AB  - Transforming growth factor (TGF)-beta promotes breast cancer metastasis to bone.
      To determine whether the osteolytic factor parathyroid hormone-related protein
      (PTHrP) is the primary mediator of the tumor response to TGF-beta, mice were
      inoculated with MDA-MB-231 breast cancer cells expressing a constitutively active
      TGF-beta type I receptor. Treatment of the mice with a PTHrP-neutralizing
      antibody greatly decreased osteolytic bone metastases. There were fewer
      osteoclasts and significantly decreased tumor area in the antibody-treated mice.
      TGF-beta can signal through both Smad and mitogen-activated protein (MAP) kinase
      pathways. Stable transfection of wild-type Smad2, Smad3, or Smad4 increased TGF
      beta-stimulated PTHrP secretion, whereas dominant-negative Smad2, Smad3, or Smad4
      only partially reduced TGF-beta-stimulated PTHrP secretion. When the cells were
      treated with a variety of protein kinases inhibitors, only specific inhibitors of
      the p38 MAP kinase pathway significantly reduced both basal and TGF-beta
      stimulated PTHrP production. The combination of Smad dominant-negative blockade
      and p38 MAP kinase inhibition resulted in complete inhibition of TGF-beta
      stimulated PTHrP production. Furthermore, TGF-beta treatment of MDA-MB-231 cells
      resulted in a rapid phosphorylation of p38 MAP kinase. Thus, the p38 MAP kinase
      pathway appears to be a major component of Smad-independent signaling by TGF-beta
      and may provide a new molecular target for anti-osteolytic therapy.

PMID- 11964408
TI  - Stepping rotation of F(1)-ATPase with one, two, or three altered catalytic sites
      that bind ATP only slowly.
AB  - F(1)-ATPase is an ATP hydrolysis-driven motor in which the gamma subunit rotates
      in the stator cylinder alpha(3)beta(3). To know the coordination of three
      catalytic beta subunits during catalysis, hybrid F(1)-ATPases, each containing
      one, two, or three "slow" mutant beta subunits that bind ATP very slowly, were
      prepared, and the rotations were observed with a single molecule level. Each
      hybrid made one, two, or three steps per 360 degrees revolution, respectively, at
      5 microm ATP where the wild-type enzyme rotated continuously without step under
      the same observing conditions. The observed dwell times of the steps are
      explained by the slow binding rate of ATP. Except for the steps, properties of
      rotation, such as the torque forces exerted during rotary movement, were not
      significantly changed from those of the wild-type enzyme. Thus, it appears that
      the presence of the slow beta subunit(s) does not seriously affect other normal
      beta subunit(s) in the same F(1)-ATPase molecule and that the order of sequential
      catalytic events is faithfully maintained even when ATP binding to one or two of
      the catalytic sites is retarded.

PMID- 11964410
TI  - Intracellular Targets of Paullones. Identification following affinity
      purification on immobilized inhibitor.
AB  - Numerous inhibitors of cyclin-dependent kinases and glycogen synthase kinase-3
      (GSK-3) are being developed in view of their potential applications against
      cancers and neurodegenerative disorders. Among these, paullones constitute a
      family of potent and apparently selective cyclin-dependent kinase and GSK-3
      inhibitors. However, their actual intracellular targets remain to be identified.
      To address this issue we have immobilized a paullone, gwennpaullone, on an
      agarose matrix. Extracts from various cell types and tissues were screened for
      proteins interacting with this matrix. This approach validated GSK-3alpha and GSK
      3beta as major intracellular paullone targets and also mitochondrial, but not
      cytoplasmic, malate dehydrogenase (MDH). Mitochondrial MDH was indeed inhibited
      by micromolar concentrations of paullones. Mitochondrial MDH was the major
      paullone-binding protein in the parasitic protozoon Leishmania mexicana, and
      paullones inhibited growth of the parasite. This simple batchwise affinity
      chromatography approach constitutes a straightforward method for the
      identification of intracellular targets of this particular class of novel anti
      mitotic compounds. It has revealed an unexpected target, mitochondrial MDH, the
      inhibition of which may participate in the pharmacological effects of paullones.

PMID- 11964409
TI  - Regulation of collagenase-3 and osteocalcin gene expression by collagen and
      osteopontin in differentiating MC3T3-E1 cells.
AB  - Both collagenase-3 and osteocalcin mRNAs are expressed maximally during the later
      stages of osteoblast differentiation. Here, we demonstrate that collagenase-3
      mRNA expression in differentiating MC3T3-E1 cells is dependent upon the presence
      of ascorbic acid, is inhibited in the presence of the collagen synthesis
      inhibitor, 3,4-dehydroproline, and is stimulated by growth on collagen in the
      absence of ascorbic acid. Transient transfection studies show that collagenase-3
      promoter activity increases during cell differentiation and requires the presence
      of ascorbic acid. Additionally, we show that, in differentiating MC3T3-E1 cells,
      collagenase-3 gene expression increases in the presence of an anti-osteopontin
      monoclonal antibody that binds near the RGD motif of this protein, whereas
      osteocalcin expression is inhibited. Furthermore, an RGD peptidomimetic compound,
      designed to block interaction of ligands to the alpha(v) integrin subunit,
      increases osteocalcin expression and inhibits collagenase-3 expression,
      suggesting that the RGD peptidomimetic initiates certain alpha(v) integrin
      signaling in osteoblastic cells. Overall, these studies demonstrate that
      stimulation of collagenase-3 expression during osteoblast differentiation
      requires synthesis of a collagenous matrix and that osteopontin and alpha(v)
      integrins exert divergent regulation of collagenase-3 and osteocalcin expression
      during osteoblast differentiation.

PMID- 11964411
TI  - Cholecystokinin induces caspase activation and mitochondrial dysfunction in
      pancreatic acinar cells. Roles in cell injury processes of pancreatitis.
AB  - Apoptosis and necrosis are critical parameters of pancreatitis, the mechanisms of
      which remain unknown. Many characteristics of pancreatitis can be studied in
      vitro in pancreatic acini treated with high doses of cholecystokinin (CCK). We
      show here that CCK stimulates apoptosis and death signaling pathways in rat
      pancreatic acinar cells, including caspase activation, cytochrome c release, and
      mitochondrial depolarization. The mitochondrial dysfunction is mediated by
      upstream caspases (possibly caspase-8) and, in turn, leads to activation of
      caspase-3. CCK causes mitochondrial alterations through both permeability
      transition pore-dependent (cytochrome c release) and permeability transition pore
      independent (mitochondrial depolarization) mechanisms. Caspase activation and
      mitochondrial alterations also occur in untreated pancreatic acinar cells;
      however, the underlying mechanisms are different. In particular, caspases protect
      untreated acinar cells from mitochondrial damage. We found that caspases not only
      mediate apoptosis but also regulate other parameters of CCK-induced acinar cell
      injury that are characteristic of pancreatitis; in particular, caspases
      negatively regulate necrosis and trypsin activation in acinar cells. The results
      suggest that the observed signaling pathways regulate parenchymal cell injury and
      death in CCK-induced pancreatitis. Protection against necrosis and trypsin
      activation by caspases can explain why the severity of pancreatitis in
      experimental models correlates inversely with the extent of apoptosis.

PMID- 11964412
TI  - Unisite and multisite catalysis in the ArsA ATPase.
AB  - The ars operon of plasmid R773 encodes an As(III)/Sb(III) extrusion pump. The
      catalytic subunit, the ArsA ATPase, has two homologous halves, A1 and A2, each
      with a consensus nucleotide-binding sequence. ATP hydrolysis is slow in the
      absence of metalloid and is accelerated by metalloid binding. ArsA M446W has a
      single tryptophan adjacent to the A2 nucleotide-binding site. Tryptophan
      fluorescence increased upon addition of ATP, ADP, or a nonhydrolyzable ATP
      analogue. Mg(2+) and Sb(III) produced rapid quenching of fluorescence with ADP,
      no quenching with a nonhydrolyzable analogue, and slow quenching with ATP. The
      results suggest that slow quenching with ATP reflects hydrolysis of ATP to ADP in
      the A2 nucleotide-binding site. In an A2 nucleotide-binding site mutant,
      nucleotides had no effect. In contrast, in an A1 nucleotide-binding mutant,
      nucleotides still increased fluorescence, but there was no quenching with Mg(2+)
      and Sb(III). This suggests that the A2 site hydrolyzes ATP only when Sb(III) or
      As(III) is present and when the A1 nucleotide-binding domain is functional. These
      results support previous hypotheses in which only the A1 nucleotide-binding
      domain hydrolyzes ATP in the absence of activator (unisite catalysis), and both
      the A1 and A2 sites hydrolyze ATP when activated (multisite catalysis).

PMID- 11964413
TI  - Calpain cleaves RhoA generating a dominant-negative form that inhibits integrin
      induced actin filament assembly and cell spreading.
AB  - Integrin-induced cell adhesion results in transmission of signals that induce
      cytoskeletal reorganizations and resulting changes in cell behavior. The
      cytoskeletal reorganizations are regulated by transient activation and
      inactivation of Rho GTPases. Previously, we identified mu-calpain as an enzyme
      that is activated by signaling across beta1 and beta3 integrins. We showed that
      it mediates cytoskeletal reorganizations in bovine aortic endothelial (BAE) and
      Chinese hamster ovary (CHO) cells and does so by acting upstream of Rac1
      activation. Here we show that mu-calpain is also involved in inactivating RhoA
      during integrin-induced signaling. Cleavage of RhoA was detectable in BAE cells
      plated on an integrin substrate; it did not occur in cells plated on poly-l
      lysine. Cleavage was inhibited by calpain inhibitors. In vitro, mu-calpain
      cleaved RhoA generating a fragment of the same size as in intact cells. The
      cleavage site was identified, an HA-tagged construct expressing calpain-cleaved
      RhoA generated, and the construct expressed in BAE and CHO cells. Calpain-cleaved
      RhoA inhibited integrin-induced stress fiber assembly and decreased cell
      spreading. Together, our data show that calpain cleaves RhoA and generates a form
      that inhibits integrin-induced stress fiber assembly and cell spreading.

PMID- 11964418
TI  - The winding road towards evidence based diagnoses.

PMID- 11964420
TI  - Social influences on birth weight.

PMID- 11964421
TI  - The teacher's teacher: a personal tribute to Alvan R Feinstein.

PMID- 11964422
TI  - Misguided efforts and future challenges for research on "diagnostic tests".

PMID- 11964423
TI  - Improving standards of medical and public health research.

PMID- 11964424
TI  - Future challenges for diagnostic research: striking a balance between simplicity
      and complexity.

PMID- 11964425
TI  - Future challenges for research on diagnostic tests: genetic tests and disease
      prevention.

PMID- 11964426
TI  - Diagnostic studies as multivariable, prediction research.

PMID- 11964427
TI  - The need for expanding and re-focusing of statistical approaches in diagnostic
      research.

PMID- 11964428
TI  - Challenges in dia-prognostic research.

PMID- 11964429
TI  - Origins and early history of the Society for Social Medicine in the UK and
      Ireland.

PMID- 11964430
TI  - Society for Social Medicine 1977-1992.

PMID- 11964431
TI  - Highly active antiretroviral treatment does not increase sexual risk behaviour
      among French HIV infected injecting drug users.
AB  - STUDY OBJECTIVE: This study examined the impact of highly active antiretroviral
      therapies (HAART) on sexual risk behaviours of HIV infected injecting drug users
      (IDUs) included in the French MANIF 2000 cohort study. DESIGN: Longitudinal
      analysis including baseline and last follow up characteristics using generalised
      estimating equations (GEE). SETTING: Hospital departments for specialist AIDS
      care in south eastern France and inner suburbs of Paris. PATIENTS: All patients
      antiretrovial treatment naive, who reported being sexually active at enrollment,
      and who had at least one follow up visit in the cohort between October 1996 and
      May 1998 (n=188). MAIN RESULTS: Of the 188 HIV infected IDUs who were
      antiretroviral treatment naive at enrollment, 34 were prescribed HAART during
      follow up. Proportion of patients who reported at least one episode of
      unprotected sexual intercourse in the previous six months only significantly
      decreased in the HAART treated group (from 47.1% to 23.5%, p=0.008, compared with
      43.5% to 35.7% in the rest of the sample, p=0.10). GEE multivariate model
      confirmed that prescription of HAART was associated with reduced sexual risk.
      CONCLUSIONS: The concern that HAART might result in clinical improvement leading
      to resumption of high risk activities that could inadvertently result in HIV
      transmission was not supported by these data. Reasons for further reductions in
      HIV risk with taking HAART remain to be clarified.

PMID- 11964432
TI  - Social class gradients in health during adolescence.
AB  - STUDY OBJECTIVE: To review existing data on social class gradients in adolescent
      health and to examine whether such gradients exist in new data concerning US
      adolescents. DESIGN: Review of relevant publications and unpublished data;
      regression analyses using adolescent self reported health status data to
      determine whether there are gradients by social class, using three classes
      categorised by adolescent reported parental work status and education.
      PARTICIPANTS: Adolescents of ages 11-17. MAIN RESULTS: Findings from the
      literature indicate the presence of social class gradients in some but not all
      aspects of adolescent health. Results from new data showed social class gradients
      in several domains of health and in profiles of health. The likelihood of being
      satisfied with one's health, of being more resilient (better family involvement,
      better problem solving, more physical activity, better home safety), having
      higher school achievement, and of being in the best health profiles were
      significantly and progressively greater as social class rose. Moreover, the
      probability of being in the poorest health profile type group was progressively
      higher as social class declined. CONCLUSIONS: The review of existing data and the
      new findings support the existence of social class gradients in satisfaction with
      one's health, in resilience to health threats, in school achievement, and in
      being in the best health overall (as manifested by the health profiles composed
      of four major domains of health). The study had two especially notable findings:
      (1) the paucity of studies using the same or similar indicators, and (2) the
      consistent existence of social class gradients in characteristics related to
      subsequent health, particularly intake of nutritional foods and physical
      activity. The sparseness of existing data and the different aspects of health
      investigated in the relatively few studies underscore the need for (1) the
      development of conceptual models specifically focused on adolescent health and
      social class; (2) additional inquiry into the measurement of social class and
      adolescent perceptions of class; (3) inclusion of contextual variables in study
      design; and (4) longitudinal cohort studies to better understand the specific
      determinants of health during adolescence.

PMID- 11964433
TI  - Migration and mortality: a 20 year follow up of Finnish twin pairs with migrant
      co-twins in Sweden.
AB  - STUDY OBJECTIVE: Finland has a higher mortality overall and for major causes of
      death than Sweden, primarily in men. The objective of this study was to analyse
      mortality in migrants from Finland to Sweden. DESIGN: A longitudinal study based
      on the Finnish Twin Cohort Study. Information about migration from Finland to
      Sweden, duration of stay in Sweden for the migrants, and deaths 1976-1995 was
      obtained from national registers. Observed numbers of deaths in migrants were
      compared with expected numbers based on the age standardised mortality experience
      of the Finnish Twin Cohort. First deaths in migrants and non-migrants of migrant
      discordant pairs were compared controlling for genetic and early childhood
      factors. PARTICIPANTS: Twin pairs of the Finnish Twin Cohort Study where at least
      one twin had migrated to Sweden (1542 twin pairs). MAIN RESULTS: Among men,
      migrants from Finland to Sweden showed an overall similar mortality compared with
      all subjects of the Finnish Twin Cohort (SMR 1.1; 95% CI 0.9 to 1.4). Mortality
      from non-violent causes was increased for migrants with at most 20 years in
      Sweden (SMR 1.9; 95% CI 1.2 to 2.6) and decreased in those with a longer stay
      (SMR 0.7; 95% CI 0.4 to 0.9). Similar results were obtained concerning first
      deaths in twin pairs discordant for migration. Among women, migrants had an
      increased mortality overall (SMR 1.4; 95% CI 1.0 to 1.8), from cardiovascular
      disease (SMR 1.7; 95% CI 1.0 to 2.7), and from violent causes (SMR 2.5; 95% CI
      1.2 to 4.6) compared with all women of the Finnish Twin Cohort. In analyses of
      migrant discordant pairs only first deaths from cardiovascular disease tended to
      be more common in the migrants than in non-migrant co-twins. CONCLUSIONS:
      Migrants from Finland to Sweden seem to have an overall mortality comparable to
      that prevailing in Finland suggesting no strong influence on mortality by the
      migration. Duration of stay seems to be associated with mortality in the
      migrants, at least in men, with a lower mortality after several years in Sweden.

PMID- 11964434
TI  - Impact of hot temperatures on death in London: a time series approach.
AB  - STUDY OBJECTIVE: This study investigated the relation between heat and mortality
      in London to determine the temperature threshold at which death rates increase
      and to quantify the effect of extreme temperatures on mortality. DESIGN: Daily
      data on all cause mortality and temperature were obtained for a 21 year period
      and the relation between them investigated both graphically and by using non
      parametric time series methods of analysis. SETTING: Greater London.
      PARTICIPANTS: Daily mortality counts in Greater London between January 1976 and
      December 1996. MAIN RESULTS: A plot of the basic mortality-temperature relation
      suggested that a rise in heat related deaths began at about 19 degrees C. Average
      temperatures above the 97th centile value of 21.5 degrees C (excluding those days
      from a 15 day "heatwave" period in 1976) resulted in an increase in deaths of
      3.34% (95% CI 2.47% to 4.23%) for every one degree increase in average
      temperature above this value. It was found that the 1976 heatwave resulted in a
      particularly large number of deaths in comparison with other hot periods.
      CONCLUSIONS: These results suggest that heat related deaths in London may begin
      at relatively low temperatures. Hot days occurring in the early part of any year
      may have a larger effect than those occurring later on; and analysis of separate
      heatwave periods suggest that episodes of long duration and of highest
      temperature have the largest mortality effect.

PMID- 11964435
TI  - Rurality, deprivation, and excess winter mortality: an ecological study.

PMID- 11964436
TI  - Trends in health inequalities by educational level in a Norwegian total
      population study.
AB  - OBJECTIVE: To describe levels of inequality and trends in self reported morbidity
      by educational level in a total Norwegian county population in the mid-1980s and
      mid-1990s. DESIGN: Two cross sectional health surveys at an interval of 10 years
      in the Nord-Trondelag Health Study, HUNT I (1984-86) and HUNT II (1995-97).
      SETTING: Primary health care, total county population study. PARTICIPANTS: Men
      and women, 25-69 years. MAIN RESULTS: There was a consistent pattern of
      increasing self reported health problems with decreasing educational level for
      three health variables: perceived health, any longstanding health problem, and
      having a chronic condition. A stable or slight decrease in inequalities over time
      was found. The prevalence odds ratio for perceived health less than good were
      2.71 for men (95% confidence intervals (CI): 2.39 to 3.09) and 2.13 for women
      (95% CI: 1.85 to 2.46) in the first survey, 2.51 for men (95% CI: 2.27 to 2.78)
      and 2.06 for women (95% CI: 1.88 to 2.26) 10 years later. CONCLUSIONS: The
      magnitude of the socioeconomic gradients in health in this population seemed
      somewhat lower than in Norway as a whole and close to the average in studies from
      other European countries. There was a slight trend towards smaller differences
      despite rapid structural changes in working life, turbulence in economy, and more
      people experiencing unemployment.

PMID- 11964437
TI  - The internal validity of a dietary pattern analysis. The Framingham Nutrition
      Studies.
AB  - STUDY OBJECTIVES: To examine the internal validity of a dietary pattern analysis
      and its ability to discriminate clusters of people with similar dietary patterns
      using independently assessed nutrient intakes and heart disease risk factors.
      DESIGN AND PARTICIPANTS: Population based study characterising dietary patterns
      using cluster analysis applied to data from the semiquantitative Framingham food
      frequency questionnaire collected from 1942 women ages 18-76 years, between 1984
      88. SETTING: Framingham, Massachusetts. MAIN RESULTS: Of 1942 women included in
      the cluster analysis, 1828 (94%) were assigned to one of the five dietary pattern
      clusters: Heart Healthy, Light Eating, Wine and Moderate Eating, High Fat, and
      Empty Calorie. Dietary patterns differed substantially in terms of individual
      nutrient intakes, overall dietary risk, heart disease risk factors, and predicted
      heart disease risk. Women in the Heart Healthy cluster had the most nutrient
      dense eating pattern, the lowest level of dietary risk, more favourable risk
      factor levels, and the lowest probability of developing heart disease. Those in
      the Empty Calorie cluster had a less nutritious dietary pattern, the greatest
      level of dietary risk, a heavier burden of heart disease risk factors, and a
      relatively higher probability of developing heart disease. Cluster
      reproducibility using discriminant analysis showed that 80% of the sample was
      correctly classified. The cluster technique was highly sensitive and specific
      (75% to 100%). CONCLUSIONS: These findings support the internal validity of a
      dietary pattern analysis for characterising dietary exposures in epidemiological
      research. The authors encourage other researchers to explore this technique when
      investigating relations between nutrition, health, and disease.

PMID- 11964438
TI  - The relation between maternal work, ambulatory blood pressure, and pregnancy
      hypertension.
AB  - STUDY OBJECTIVE: The purpose of the study was to determine the relations between
      maternal work, ambulatory blood pressure in mid-pregnancy, and subsequent
      pregnancy outcome. DESIGN: Data were studied on 933 healthy normotensive
      primigravidas who had been enrolled into a study on the predictive value of
      ambulatory blood pressure measurement performed between 18 and 24 weeks
      gestation. They were classified into three groups depending on whether they were
      at work (working group, n=245), not working (not working group, n=289), or
      normally employed but chose not to work (ENK group, n=399), on the day monitoring
      was performed. SETTING: The Rotunda Hospital (a large maternity hospital),
      Dublin, Ireland. MAIN RESULTS: Adjusted for age, body mass index, smoking,
      drinking, and marital status, women at work had higher mean daytime systolic
      (p<0.01) and diastolic (p<0.01) and 24 hour systolic pressures (p=0.03) compared
      with those not working. The rate of subsequent development of pre-eclampsia was
      significantly higher (odds ratio 4.1, 95% CI 1.1 to 15.2, p=0.03) among those at
      work compared with those not working. The association between pre-eclampsia and
      maternal work remained significant (odds ratio 5.5, 95% CI 1.1 to 27.8, p=0.04)
      even after allowing for the confounding factors of age, smoking, body mass index,
      and marital status. When daytime systolic and diastolic blood pressure were added
      to the regression analysis the risk ratios for pre-eclampsia remained high but
      did not quite reach statistical significance (odds ratio 4.7, 0.90 to 24.8,
      p=0.066). Birth weight and placental weight were not predicted by work status or
      blood pressure. CONCLUSIONS: A significant independent relation was found between
      maternal work and ambulatory blood pressure levels in mid-pregnancy. In addition,
      it was found that maternal work was significantly associated with the subsequent
      development of pre-eclampsia

PMID- 11964439
TI  - Influence of driver nationality on the risk of causing vehicle collisions in
      Spain.
AB  - STUDY OBJECTIVE: To estimate the association between driver nationality and the
      risk of causing a collision between vehicles in motion. DESIGN: Retrospective,
      matched by collision, case-control study. SETTING: Collisions that occurred in
      Spain during the period from 1990 to 1999 were studied. PARTICIPANTS: Responsible
      (case) and non-responsible (control) drivers identified in the databases of the
      Direccion General de Trafico (General Traffic Directorate) who were involved in a
      collisions between two or more four wheeled vehicles in motion, in which only one
      of the drivers had committed a traffic violation. MAIN RESULTS: Crude odds ratios
      (ORs) for the effect of driver nationality on the risk of causing a collision
      were significantly higher for foreign drivers than for Spanish drivers, and
      ranged from a minimum of 1.19 (95% CI 1.09 to 1.29) for Portuguese drivers to a
      maximum of 2.06 (1.88 to 2.27) for British drivers. Corresponding adjusted ORs
      were slightly lower, but were still significantly higher than 1 for all
      nationalities except Italian, Belgian, and American (USA). Adjusted ORs were
      usually higher for collisions that occurred in urban areas than on open roads.
      CONCLUSIONS: Authorities responsible for traffic safety, and drivers in general,
      should consider foreign drivers in Spain at particularly high risk for causing
      collisions, especially in urban areas.

PMID- 11964440
TI  - Decreasing AIDS mortality rates among young adults in the city of Florence, 1987
      1999.

PMID- 11964441
TI  - Mantophasmatodea: a new insect order with extant members in the Afrotropics.
AB  - A new insect order, Mantophasmatodea, is described on the basis of museum
      specimens of a new genus with two species: Mantophasma zephyra gen. et sp. nov.
      (one female from Namibia) and M. subsolana sp. nov. (one male from Tanzania).
      This is the first time since 1914 that a newly described extant insect taxon has
      proved unplaceable within a recognized order. Mantophasmatodeans are apterous
      carnivores. Their closest phylogenetic relationships may be to Grylloblattodea
      (ice-crawlers) and/or Phasmatodea (stick insects), but the morphological evidence
      is ambiguous. Raptophasma Zompro from Baltic amber is assigned to the
      Mantophasmatodea, revealing a wider previous range for the lineage.

PMID- 11964444
TI  - The International Space Station at risk.

PMID- 11964443
TI  - C-cadherin ectodomain structure and implications for cell adhesion mechanisms.
AB  - Cadherins are transmembrane proteins that mediate adhesion between cells in the
      solid tissues of animals. Here we present the 3.1 angstrom resolution crystal
      structure of the whole, functional extracellular domain from C-cadherin, a
      representative "classical" cadherin. The structure suggests a molecular mechanism
      for adhesion between cells by classical cadherins, and it provides a new
      framework for understanding both cis (same cell) and trans (juxtaposed cell)
      cadherin interactions. The trans adhesive interface is a twofold symmetric
      interaction defined by a conserved tryptophan side chain at the membrane-distal
      end of a cadherin molecule from one cell, which inserts into a hydrophobic pocket
      at the membrane-distal end of a cadherin molecule from the opposing cell.

PMID- 11964446
TI  - Arctic drilling. A modest drop in a big bucket.

PMID- 11964445
TI  - Conservation science. Caribou study fuels debate on drilling in Arctic Refuge.

PMID- 11964447
TI  - Entomology. New insect order speaks to life's diversity.

PMID- 11964448
TI  - Amphibian decline. Ubiquitous herbicide emasculates frogs.

PMID- 11964449
TI  - Scientific misconduct. Beijing U. issues first-ever rules.

PMID- 11964451
TI  - Chemistry. To net big molecules, widen the mesh.

PMID- 11964450
TI  - Scientific misconduct. Australia probes kidney researcher.

PMID- 11964452
TI  - Parkinson's disease. Coincidence or connection?

PMID- 11964453
TI  - Environmental health. National tracking plan picks up speed.

PMID- 11964454
TI  - Biomedical research. Dexter to step down at Wellcome Trust.

PMID- 11964455
TI  - United Kingdom. Hard sciences in terminal decline?

PMID- 11964456
TI  - Glacial research. Melting glaciers release ancient relics.

PMID- 11964458
TI  - Daniel Pauly profile. Going to the edge to protect the sea.

PMID- 11964457
TI  - Immunology. Gently soothing a savage immune system.

PMID- 11964459
TI  - Daniel Pauly profile. Science helps Pew push its oceans agenda.

PMID- 11964460
TI  - American Chemical Society meeting. Science invades the Magic Kingdom.

PMID- 11964461
TI  - Research and development. A new "industrial ecology".

PMID- 11964462
TI  - Biomedicine. Back to an aspirin a day?

PMID- 11964463
TI  - Geology. Osmium remembers.

PMID- 11964464
TI  - Computing. Successes and challenges.

PMID- 11964465
TI  - Transcription. Proteasome parts at gene promoters.

PMID- 11964466
TI  - Immunology. T before NK.

PMID- 11964468
TI  - Climate modeling. How accurate are climate simulations?

PMID- 11964467
TI  - Parasitology. When the host is smarter than the parasite.

PMID- 11964469
TI  - Seismic anisotropy: tracing plate dynamics in the mantle.
AB  - Elastic anisotropy is present where the speed of a seismic wave depends on its
      direction. In Earth's mantle, elastic anisotropy is induced by minerals that are
      preferentially oriented in a directional flow or deformation. Earthquakes
      generate two seismic wave types: compressional (P) and shear (S) waves, whose
      coupling in anisotropic rocks leads to scattering, birefringence, and waves with
      hybrid polarizations. This varied behavior is helping geophysicists explore rock
      textures within Earth's mantle and crust, map present-day upper-mantle
      convection, and study the formation of lithospheric plates and the accretion of
      continents in Earth history.

PMID- 11964470
TI  - Allergy, parasites, and the hygiene hypothesis.
AB  - The increase of allergic diseases in the industrialized world has often been
      explained by a decline in infections during childhood. The immunological
      explanation has been put into the context of the functional T cell subsets known
      as T helper 1 (TH1) and T helper 2 (TH2) that display polarized cytokine
      profiles. It has been argued that bacterial and viral infections during early
      life direct the maturing immune system toward TH1, which counterbalance
      proallergic responses of TH2 cells. Thus, a reduction in the overall microbial
      burden will result in weak TH1 imprinting and unrestrained TH2 responses that
      allow an increase in allergy. This notion is contradicted by observations that
      the prevalence of TH1-autoimmune diseases is also increasing and that TH2-skewed
      parasitic worm (helminth) infections are not associated with allergy. More
      recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that
      occur during long-term helminth infections have been shown to be inversely
      correlated with allergy. The induction of a robust anti-inflammatory regulatory
      network by persistent immune challenge offers a unifying explanation for the
      observed inverse association of many infections with allergic disorders.

PMID- 11964471
TI  - Murine leukemia induced by retroviral gene marking.

PMID- 11964472
TI  - Multicolor and electron microscopic imaging of connexin trafficking.
AB  - Recombinant proteins containing tetracysteine tags can be successively labeled in
      living cells with different colors of biarsenical fluorophores so that older and
      younger protein molecules can be sharply distinguished by both fluorescence and
      electron microscopy. Here we used this approach to show that newly synthesized
      connexin43 was transported predominantly in 100- to 150-nanometer vesicles to the
      plasma membrane and incorporated at the periphery of existing gap junctions,
      whereas older connexins were removed from the center of the plaques into
      pleiomorphic vesicles of widely varying sizes. Selective imaging by correlated
      optical and electron microscopy of protein molecules of known ages will clarify
      fundamental processes of protein trafficking in situ.

PMID- 11964474
TI  - Superplumes from the core-mantle boundary to the lithosphere: implications for
      heat flux.
AB  - Three-dimensional modeling of upper-mantle anelastic structure reveals that
      thermal upwellings associated with the two superplumes, imaged by seismic elastic
      tomography at the base of the mantle, persist through the upper-mantle transition
      zone and are deflected horizontally beneath the lithosphere. This explains the
      unique transverse shear wave isotropy in the central Pacific. We infer that the
      two superplumes may play a major and stable role in supplying heat and horizontal
      flow to the low-viscosity asthenospheric channel, lubricating plate motions and
      feeding hot spots. We suggest that more heat may be carried through the core
      mantle boundary than is accounted for by hot spot fluxes alone.

PMID- 11964473
TI  - External reflection from omnidirectional dielectric mirror fibers.
AB  - We report the design and fabrication of a multilayered macroscopic fiber preform
      and the subsequent drawing and optical characterization of extended lengths of
      omnidirectional dielectric mirror fibers with submicrometer layer thickness. A
      pair of glassy materials with substantially different indices of refraction, but
      with similar thermomechanical properties, was used to construct 21 layers of
      alternating refractive index surrounding a tough polymer core. Large directional
      photonic band gaps and high reflection efficiencies comparable to those of the
      best metallic reflectors were obtained. Potential applications of these fibers
      include woven fabrics for radiation barriers, spectral authentication of cloth,
      and filters for telecommunications.

PMID- 11964475
TI  - Evidence for an ancient osmium isotopic reservoir in Earth.
AB  - Iridosmine grains from placer deposits associated with peridotite-bearing
      ophiolites in the Klamath mountains have extremely radiogenic 186Os/188Os ratios
      and old Re-Os minimum ages, from 256 to 2644 million years. This indicates the
      existence of an ancient platinum group element reservoir with a supra-chondritic
      Pt/Os ratio. Such a ratio may be produced in the outer core as a result of inner
      core crystallization that fractionates Os from Pt. However, if the iridosmine Os
      isotopic compositions are a signature of the outer core, then the inner core must
      have formed very early, within several hundred million years after the accretion
      of Earth.

PMID- 11964476
TI  - Ultrapermeable, reverse-selective nanocomposite membranes.
AB  - Polymer nanocomposites continue to receive tremendous attention for application
      in areas such as microelectronics, organic batteries, optics, and catalysis. We
      have discovered that physical dispersion of nonporous, nanoscale, fumed silica
      particles in glassy amorphous poly(4-methyl-2-pentyne) simultaneously and
      surprisingly enhances both membrane permeability and selectivity for large
      organic molecules over small permanent gases. These highly unusual property
      enhancements, in contrast to results obtained in conventional filled polymer
      systems, reflect fumed silica-induced disruption of polymer chain packing and an
      accompanying subtle increase in the size of free volume elements through which
      molecular transport occurs, as discerned by positron annihilation lifetime
      spectroscopy. Such nanoscale hybridization represents an innovative means to tune
      the separation properties of glassy polymeric media through systematic
      manipulation of molecular packing.

PMID- 11964477
TI  - The cause of carbon isotope minimum events on glacial terminations.
AB  - The occurrence of carbon isotope minima at the beginning of glacial terminations
      is a common feature of planktic foraminifera carbon isotopic records from the
      Indo-Pacific, sub-Antarctic, and South Atlantic. We use the delta13C record of a
      thermocline-dwelling foraminifera, Neogloboquadrina dutertrei, and surface
      temperature estimates from the eastern equatorial Pacific to demonstrate that the
      onset of delta13C minimum events and the initiation of Southern Ocean warming
      occurred simultaneously. Timing agreement between the marine record and the
      delta13C minimum in an Antarctic atmospheric record suggests that the deglacial
      events were a response to the breakdown of surface water stratification, renewed
      Circumpolar Deep Water upwelling, and advection of low delta13C waters to the
      convergence zone at the sub-Antarctic front. On the basis of age agreement
      between the absolute delta13C minimum in surface records and the shift from low
      to high delta13C in the deep South Atlantic, we suggest that the delta13C rise
      that marks the end of the carbon isotope minima was due to the resumption of
      North Atlantic Deep Water influence in the Southern Ocean.

PMID- 11964478
TI  - Control of the selectivity of the aquaporin water channel family by global
      orientational tuning.
AB  - Aquaporins are transmembrane channels found in cell membranes of all life forms.
      We examine their apparently paradoxical property, facilitation of efficient
      permeation of water while excluding protons, which is of critical importance to
      preserving the electrochemical potential across the cell membrane. We have
      determined the structure of the Escherichia coli aquaglyceroporin GlpF with bound
      water, in native (2.7 angstroms) and in W48F/F200T mutant (2.1 angstroms) forms,
      and carried out 12-nanosecond molecular dynamics simulations that define the
      spatial and temporal probability distribution and orientation of a single file of
      seven to nine water molecules inside the channel. Two conserved asparagines force
      a central water molecule to serve strictly as a hydrogen bond donor to its
      neighboring water molecules. Assisted by the electrostatic potential generated by
      two half-membrane spanning loops, this dictates opposite orientations of water
      molecules in the two halves of the channel, and thus prevents the formation of a
      "proton wire," while permitting rapid water diffusion. Both simulations and
      observations revealed a more regular distribution of channel water and an
      increased water permeability for the W48F/F200T mutant.

PMID- 11964479
TI  - DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through
      the Gadd45 protein.
AB  - The signaling pathway from phosphoinositide 3-kinase to the protein kinase Akt
      controls organismal life-span in invertebrates and cell survival and
      proliferation in mammals by inhibiting the activity of members of the FOXO family
      of transcription factors. We show that mammalian FOXO3a also functions at the G2
      to M checkpoint in the cell cycle and triggers the repair of damaged DNA. By gene
      array analysis, FOXO3a was found to modulate the expression of several genes that
      regulate the cellular response to stress at the G2-M checkpoint. The growth
      arrest and DNA damage response gene Gadd45a appeared to be a direct target of
      FOXO3a that mediates part of FOXO3a's effects on DNA repair. These findings
      indicate that in mammals FOXO3a regulates the resistance of cells to stress by
      inducing DNA repair and thereby may also affect organismal life-span.

PMID- 11964480
TI  - Local actin polymerization and dynamin recruitment in SV40-induced
      internalization of caveolae.
AB  - Simian virus 40 (SV40) utilizes endocytosis through caveolae for infectious entry
      into host cells. We found that after binding to caveolae, virus particles induced
      transient breakdown of actin stress fibers. Actin was then recruited to virus
      loaded caveolae as actin patches that served as sites for actin "tail" formation.
      Dynamin II was also transiently recruited. These events depended on the presence
      of cholesterol and on the activation of tyrosine kinases that phosphorylated
      proteins in caveolae. They were necessary for formation of caveolae-derived
      endocytic vesicles and for infection of the cell. Thus, caveolar endocytosis is
      ligand-triggered and involves extensive rearrangement of the actin cytoskeleton.

PMID- 11964481
TI  - Role of prostacyclin in the cardiovascular response to thromboxane A2.
AB  - Thromboxane (Tx) A2 is a vasoconstrictor and platelet agonist. Aspirin affords
      cardioprotection through inhibition of TxA2 formation by platelet cyclooxygenase
      (COX-1). Prostacyclin (PGI2) is a vasodilator that inhibits platelet function.
      Here we show that injury-induced vascular proliferation and platelet activation
      are enhanced in mice that are genetically deficient in the PGI2 receptor (IP) but
      are depressed in mice genetically deficient in the TxA2 receptor (TP) or treated
      with a TP antagonist. The augmented response to vascular injury was abolished in
      mice deficient in both receptors. Thus, PGI2 modulates platelet-vascular
      interactions in vivo and specifically limits the response to TxA2. This interplay
      may help explain the adverse cardiovascular effects associated with selective COX
      2 inhibitors, which, unlike aspirin and nonsteroidal anti-inflammatory drugs
      (NSAIDs), inhibit PGI2 but not TxA2.

PMID- 11964482
TI  - Optical projection tomography as a tool for 3D microscopy and gene expression
      studies.
AB  - Current techniques for three-dimensional (3D) optical microscopy (deconvolution,
      confocal microscopy, and optical coherence tomography) generate 3D data by
      "optically sectioning" the specimen. This places severe constraints on the
      maximum thickness of a specimen that can be imaged. We have developed a
      microscopy technique that uses optical projection tomography (OPT) to produce
      high-resolution 3D images of both fluorescent and nonfluorescent biological
      specimens with a thickness of up to 15 millimeters. OPT microscopy allows the
      rapid mapping of the tissue distribution of RNA and protein expression in intact
      embryos or organ systems and can therefore be instrumental in studies of
      developmental biology or gene function.

PMID- 11964483
TI  - Divergent regulation of dihydrofolate reductase between malaria parasite and
      human host.
AB  - For half a century, successful antifolate therapy against Plasmodium falciparum
      malaria has been attributed to host-parasite differences in drug binding to
      dihydrofolate reductase-thymidylate synthase (DHFR-TS). Selectivity may also
      arise through previously unappreciated differences in regulation of this drug
      target. The DHFR-TS of Plasmodium binds its cognate messenger RNA (mRNA) and
      inhibits its own translation. However, unlike translational regulation of DHFR or
      TS in humans, DHFR-TS mRNA binding is not coupled to enzyme active sites. Thus,
      antifolate treatment does not relieve translational inhibition and parasites
      cannot replenish dead enzyme.

PMID- 11964484
TI  - Recruitment of a 19S proteasome subcomplex to an activated promoter.
AB  - The 19S proteasome regulatory particle plays a critical role in cellular
      proteolysis. However, recent reports have demonstrated that 19S proteins play a
      nonproteolytic role in nucleotide excision repair and transcription elongation.
      We show by chromatin immunoprecipitation assays that proteins comprising the 19S
      complex are recruited to the GAL1-10 promoter by the Gal4 transactivator upon
      induction with galactose. This recruited complex does not contain proteins from
      the 20S proteolytic particle and includes a subset of the 19S proteins. This
      subset is also specifically retained from an extract by the Gal4 activation
      domain. These data indicate that in vivo, the base of the 19S complex functions
      independently of the larger complex and plays a direct, nonproteolytic role in
      RNA polymerase II transcription.

PMID- 11964485
TI  - Tech.Sight. A technique whose time has come.

PMID- 11964486
TI  - Mental health costs and outcomes under alternative capitation systems in
      Colorado: early results.
AB  - BACKGROUND: This study presents preliminary findings for the first nine months of
      the State of Colorado USA Medicaid capitation Pilot Project. Two different models
      of capitation (model I and model II) are compared with fee for service (FFS) in
      providing services to severely and persistently mentally ill adults. In model I
      the state's mental health authority contracts with community mental health
      centers (CMHCs) who both manage the care and deliver mental health services,
      while in model II the state contracted with a joint venture between a for-profit
      managed care firm who manage the care with either a single CMHC or an alliance of
      CMHCs who deliver the mental health services. AIMS: Our objective is to examine
      utilization, cost and outcomes of inpatient and outpatient (including community
      based) services before and after the implementation of a capitated payment system
      for Colorado's Medicaid mental health services compared to services that remained
      under FFS reimbursement. METHODS: The stratified, random sample includes 513
      consumers (188 for model I, 179 for model II, and 146 for FFS). Consumer outcomes
      were collected by trained interviewers and include 17 measures of symptoms,
      health status, functioning, quality of life and consumer satisfaction.
      Utilization and cost of services are from the Medicaid claims data and a shadow
      billing data system (post-capitation) designed by Colorado. The first step of the
      two-step regression procedure adjusts for the presence of individuals with use or
      no service use during the specified time while the second step, ordinary least
      squares regression, is applied to the sample who utilized services. RESULTS:
      These preliminary findings indicate consistent reductions in inpatient user costs
      and probability of outpatient use under capitation. Combining all services, there
      are consistent reductions in the probability of use in both models: model I had
      significantly higher initial probability of use for any service. Only model II
      showed a statistically significant decrease in post-capitation overall user
      costs, but they were initially higher than model I or FFS. Estimated total cost
      per person for model I suggests virtually no change from the pre- to post
      capitation period. Model II had the highest pre-capitation and the lowest post
      capitation estimated cost per person. Examination of pre measures of outcomes
      across capitated areas suggest that samples drawn from the FFS, model I and model
      II areas were comparable in severity of psychiatric symptoms, functioning, health
      status and quality of life. No changes were found in outcomes. DISCUSSION: These
      early findings are consistent with the limited literature on capitation. Both
      studies of capitation integrated with medical care and those specific to mental
      health settings did not find adverse changes in outcomes compared to FFS.
      Limitations include the short follow-up period, lack of detail and possible under
      reporting of outpatient services provided by the shadow billing data system.
      CONCLUSIONS: For the short term, it is concluded that capitation can reduce
      service cost per person without significant change in clinical status.
      IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Implications are unclear until we
      can determine whether (i) reductions in the numbers receiving service indicates
      favorable consumer outcomes or reductions in access and (ii) lack of change in
      consumer outcomes is due to the benefits of capitation or the lack of sensitivity
      of the outcome measures. IMPLICATIONS FOR HEALTH CARE POLICY FORMULATION:
      Implications are premature for these early findings. IMPLICATIONS FOR FUTURE
      RESEARCH: Future research should include longer follow-up as well as analysis of
      long-term consequences for both cost savings and clinical outcomes.

PMID- 11964487
TI  - Issues in the design of studies for the economic evaluation of new atypical
      antipsychotics: the ESTO study.
AB  - BACKGROUND: Increasing attention is being focused on the costs of healthcare and
      the need for cost-effective treatments. Drugs for schizophrenia have not escaped
      this scrutiny, especially now that several new agents are available, with
      acquisition costs substantially higher than for established therapies. However,
      most of the existing evaluations of new drugs for schizophrenia have weak
      designs, either comparing health care costs before and after introduction of the
      new drug, or being based on modelling approaches incorporating numerous
      assumptions. AIM OF THE STUDY: The aim of the study was to discuss and resolve
      the key design issues in the planning of a prospective randomized trial to assess
      the socio-economic impact of a new atypical antipsychotic (quetiapine). METHODS:
      Key methodological issues were identified and discussed in the context of the
      economic evaluation being planned. These were patient recruitment and entry
      criteria, selection of comparator drug, blinding of doctor and patient, range of
      socio-economic outcomes, length of follow-up and sample size. RESULT: The
      resulting economic evaluation, the ESTO study, was an international multi-centre
      randomized controlled trial, with concurrent data collection for a wide range of
      clinical, economic and quality of life outcomes. The trial had a pragmatic
      design, enrolling patients experiencing an acute exacerbation on existing
      therapy. In addition to the presenting exacerbation, patients must have had at
      least one hospitalization or documented evidence of exacerbation within the
      previous three years. On admission to the study, existing psychotic medication
      was withdrawn prior to randomization to quetiapine or haloperidol. Doses of both
      drugs were titrated up to an optional dose, with flexibility for additional
      increases if required. Both patients and doctors were blinded to treatment
      allocations, on the grounds that, since quetiapine was still in development,
      unblinded assessments of efficacy would not be credible. Patients were followed
      for 1 year, irrespective of whether they withdrew from study medication. A wide
      range of socio-economic outcomes was assessed, including costs falling on the
      healthcare sector, other agencies and the family. In addition data were collected
      on patients' earnings and quality of life, measured by the Short-Form 36 health
      profile. Data were also collected on a range of clinical measures, such as the
      Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions
      (CGI), the AIMS neurological rating scale and the neurological rating scale of
      Simpson and Angus. This was to assess whether changes in socio-economic end
      points were indeed matched by changes in the patient's clinical condition.
      CONCLUSIONS: The design of studies such as ESTO is inevitably a compromise
      between control and pragmatism. For example, whilst blinding of doctor and
      patient may reduce potential bias, this may cause difficulty with compliance
      owing to the use of additional dummy medications. Despite these compromises, the
      ESTO study should provide a more reliable assessment of the socio-economic
      outcomes of a new anti-psychotic and has attracted the widespread support of
      analysts and investigators. It has already served as a template for other studies
      and, if the methodology is successful, will have implications for the assessment
      of similar drugs in the future

PMID- 11964488
TI  - Cost benefits of substance abuse treatment: an overview of results from alcohol
      and drug abuse.
AB  - BACKGROUND AND METHODS: The treatment of substance abuse is an important health
      service available in all industrialized countries throughout the world. Cost of
      treatment and its benefit or economic value is an important policy issue.
      Reduction in health care cost is one alternative way to measure benefits. This
      paper reviews a series of studies (all from the US) which address the cost
      benefit question. Most studies have compared the monthly costs prior to
      initiation of substance abuse treatment with the costs following initiation.
      RESULTS FROM STUDIES OF ALCOHOLISM TREATMENT: Many studies have found that, over
      the time prior to alcoholism treatment initiation, total monthly health care
      costs increased and costs substantially increased during the 6-12 months prior to
      treatment. Following treatment initiation, monthly total medical care costs
      declined and the overall trend was downward, i.e., the slope was negative. In
      contrast to the use of general health care where women typically utilize more
      medical care than men, overall medical care costs were found to be similar.
      Alcoholics of different ages, however, showed distinct medical care costs, i.e.,
      younger patients experienced greater declines in medical care costs following
      alcoholism treatment initiation. Inpatient treatment is most affected by
      alcoholism treatment. In some cases, outpatient treatment is actually increased
      in response to aftercare health care utilization, but at a substantially lower
      cost than inpatient treatment. If the alcoholism condition can be treated on an
      outpatient basis, then the total cost of such treatment is obviously lower and
      the potential for a cost-offset net effect is substantially increased. COST
      BENEFITS OF DRUG ABUSE TREATMENT: There have been few drug abuse treatment cost
      benefit research studies. Early studies found that there was a decline in
      sickness and medical care utilization associated with initiation of treatment. A
      recent study found a substantial reduction in total health care costs following
      initiation of drug abuse treatment. Utilization of inpatient care and its
      associated costs are most affected by the absence and/or presence of treatment.
      SUMMARY AND CONCLUSION: This review describes the research findings from a number
      of cost-offset or cost-benefit studies of alcoholism and drug abuse treatment. In
      broad terms the findings of this research can be summarized as follows. (i)
      Untreated alcoholics or drug dependent persons use health care and incur costs at
      a rate about twice that of their age and gender cohorts. (ii) Once treatment
      begins, total health care utilization and costs begin to drop, reaching a level
      that is lower than pre-treatment initiation costs after a two- to four-year
      period. The conclusion is based on similar findings across different patient
      populations using a variety of research designs. (iii) There are no apparent
      gender differences in the utilization and associated costs before and after
      treatment initiation. (iv) There are age differences that support the value of
      early intervention. Younger treated substance abuse patients have pre-treatment
      total cost levels that are lower than pre-treatment levels for older patients.
      IMPLICATIONS OF HEALTH POLICY: The results of research provide consistent support
      for the cost benefits of substance abuse treatment. From a health policy
      perspective, such results are promising if the objective is to demonstrate that
      treatment investment can pay for all or part of its associated costs through
      reductions in other health care costs. One can hold a contrary position, i.e.,
      lower future medical care costs for substance abusers could reflect denial of
      essential care. IMPLICATIONS FOR FURTHER RESEARCH: The studies that have
      addressed the potential cost offset of substance abuse treatment have been
      largely based upon overall or aggregate effects across all forms of substance
      abuse treatment. There have been no studies of the cost offset of specific
      treatment modalities, though this is what the next generation of studies should
      do

PMID- 11964489
TI  - Relating personnel costs in special care units and in traditional care units to
      resident characteristics.
AB  - BACKGROUND: There are over 16 000 nursing homes in the United States (US), among
      which approximately 70% of residents are cognitively impaired. Reflecting this,
      approximately 20% of US nursing homes maintain Special Dementia Care Units
      (SCUs). SCUs supposedly provide more staff time and more specialized staff
      assignments to residents than do traditional care units. AIMS OF THE STUDY: This
      paper addresses the issues of staff time and assignment: do the costs of personal
      care inputs differ according to whether they are provided by SCUs or in
      traditional care settings? Related to this, are differences associated with the
      different settings, or are they accounted for by resident characteristics within
      the settings? METHODS: Given the bias generally associated with collection of
      staff time data, the author developed (supported by the Health Care Financing
      Administration and the National Institute on Aging) and used in this study a
      barcode-based system ('InfoAide'). Using InfoAide, each provider automatically
      recorded task- and resident-specific time expenditure data which were
      subsequently monetized, using prevailing local wage rates. Individual resident
      personal characteristics and status data were provided by another simultaneous
      study of SCU impacts among the same residents. Regression analysis (MANCOVA for
      significantly correlated dependent variables) was used to examine the
      relationships between cost and SCU/traditional status, and individual resident
      characteristics, separately for each category of provider. RESULTS: Controlling
      for resident characteristics, the cost of aide care is significantly (positively)
      related (p <=0.01) to SCU status. Cognitive impairment, ADL impairment and being
      restrained are also related to higher aide care cost (p <=0.05, p <=0.01, and p
      <=0.05, respectively). The same is generally true of Speech Therapy, Social
      Service and care by licensed practical nurses, although the differences between
      SCU and traditional care units are essentially trivial - and there are no
      SCU/traditional care differences for registered nurses. DISCUSSION:
      SCU/traditional unit status, even when combined with the central resident
      covariates, explains very little variance in service costs, other than among
      nursing aides; in separate MR analyses in which monetized service time was the
      dependent variable, the cumulative adjusted R2 among aides was 0.37; for each of
      the other categories of service provider, the adjusted R2 was less than 0.10.
      There were differences (particularly in cognitive and ADL impairment) between SCU
      and non-SCU residents; these differences were related to differences in basic
      services which were, in turn, provided primarily by aides. The increased level of
      care provided in SCUs is attributable primarily to nursing aides. However, there
      is relatively little (albeit statistically significant) variation in more
      'elective'services according to individual characteristics or to SCU versus
      traditional unit placement. This discussion is limited by the absence of analyses
      of possible interactions among variables, and by the cross-sectional nature of
      the data presented here. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: This
      absence of a substantial relationship between SCU/traditional status suggests
      that dichotomization between SCU and traditional care is misplaced, and that more
      attention should perhaps be given to the targeting and tailoring of services
      related to individual gradations of impairment and need. IMPLICATIONS FOR HEALTH
      POLICY FORMULATIONS: A very considerable literature has developed recently
      pertaining to Special versus Traditional care for persons with dementing illness.
      These data suggest that this is not a fruitful distinction, and that more effort
      should be devoted to defining and quantifying the elements and quality of care
      provided to nursing home residents. IMPLICATIONS FOR FURTHER RESEARCH: Further
      research is needed into the components of optimal quality care for demented
      nursing home residents, and into the interaction among these components as they
      relate to resident outcomes.

PMID- 11964490
TI  - Cost-effectiveness of SSRIs: a European perspective.
AB  - BACKGROUND: Evaluating treatments for depression is of great importance given
      that estimates of lifetime prevalence range up to 20 per cent. The class of
      antidepressants known as Selective Serotonin Reuptake Inhibitors (SSRIs) has been
      a major innovation in this area, but has also raised questions about their cost
      effectiveness as a first-line treatment, due to their high price compared to
      other drugs. AIMS OF THE STUDY: The study aimed to contribute to this debate,
      from within the context of European health care systems. These systems share a
      common set of pressures to contain costs, many of which, in Europe, are funded
      from public finances, unlike the US system, with its greater private sector
      involvement. METHODS: A range of published papers were reviewed. They all covered
      the general area of costs and SSRIs and were evaluated in a European context.
      RESULTS: Some studies have considered the possible use of SSRIs purely as a
      matter of accounting costs. Not surprisingly, they have argued against switching,
      on the grounds of high acquisition costs. However, studies based alongside
      clinical trials have incorporated efficacy into the analysis. They have produced
      cost-effectiveness or cost utility based arguments in favour of the SSRIs or
      other innovative, high-price antidepressants. Another approach has used
      retrospective analysis of real patients'experience of treatment. This has shown
      that, if the full costs of treatment are considered, there is an argument for
      switching from Tricyclic Antidepressants (TCAs) to first-line use of SSRIs. Most
      economic evaluations have used decision analysis techniques and thus are subject
      to all the qualifications that apply to such modelling exercises. With only one
      exception, all the studies in this category were in favour of switching to newer
      antidepressants. While efficacy was generally accepted as roughly equal, the
      newer products were seen as less toxic and better tolerated. The consequence was
      savings in health care costs that outweighed the increase in drug acquisition
      costs. DISCUSSION: The economic evaluation papers in this review have almost all
      challenged the view that health care providers should regard SSRIs as 'too
      expensive' for widespread use. Instead, if one integrates clinical outcomes with
      a full range of health care costs the high-price products may be more cost
      effective. Certainly that is the message from this review, although the
      observations must be qualified, as most of the studies considered were UK based.
      CONCLUSIONS: In all health care systems there are now incentives to control
      costs, which may act as a disincentive to the use of SSRIs, but if those
      responsible for drug budgets also have financial responsibilities outside the
      drug budget they will also have an incentive to control those areas. In this
      case, there is a body of evidence to suggest they would gain by switching to
      SSRIs. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Decisions on favoured
      classes of antidepressant for first-line treatment should not be made purely on
      the basis of drug costs. The implications for all aspects of health spending
      should be included in the deliberations. IMPLICATIONS FOR HEALTH POLICY
      FORMULATION: The impact of spending across all budgets should be considered when
      drawing up policy on the use of new health care technologies, such as the SSRIs.
      IMPLICATIONS FOR FURTHER RESEARCH: Most studies in this area have used modelling
      techniques, which are subject to a number of limitations. They have also used
      results taken from the artificial environment of clinical trials. Future research
      should aim to generate economic evaluations based on effectiveness amongst real
      patients in clinical practice.

PMID- 11964491
TI  - Economics and ethics in mental health care: traditions and trade-offs.
AB  - BACKGROUND: Both economic and ethical perspectives are exerting increasing
      influence at all levels of mental health policy and practice; yet there is little
      consensus on how these two different perspectives are to be reconciled or
      explicitly incorporated into decision-making. AIM: This review article is
      directed towards a fuller understanding of the complex trade-offs and compromises
      that are or may be made by clinicians, managers and policy-makers alike in the
      context of mental health care planning and delivery. METHOD: We briefly outline a
      number of key principles of health care economics and ethics, and then focus on
      the particular incentives and trade-offs that are raised by these principles at
      three levels of the mental health system: government and society; purchasers and
      providers; and users and carers. RESULTS: At the level of government and society,
      we find (economically influenced) attempts to reform mental health care offset by
      concerns revolving around access to care: whether society is prepared to forgo
      economic benefits in exchange for improved equity depends to a considerable
      extent on the prevailing ethical paradigm. The implementation of these reforms at
      the level of purchasers and providers has helped to focus attention on evaluation
      and prioritization, but has also introduced "perverse incentives" such as cost
      shifting and cream-skimming, which can impede access to or continuity of
      appropriate care for mentally ill people. Finally, we detect opportunities for
      moral hazard and other forms of strategic behaviour that are thrown up by the
      nature of the carer:user relationship in mental health care. CONCLUSION: We
      conclude by highlighting the need to move towards a more open, accountable and
      evidence-based mental health care system. Acknowledgement of and progress towards
      these three requirements will not deliver ideal levels of efficiency or equity,
      but will foster a greater understanding of the relevance of ethical
      considerations to mental health policies and strategies that are often influenced
      strongly or solely by economic arguments, whilst also demonstrating that equity
      must come at a price.

PMID- 11964492
TI  - The economic benefits of supported employment for persons with mental illness.
AB  - BACKGROUND: Policies and programs that emphasize employment for persons with
      mental illness are often promoted with the goals of improving economic self
      sufficiency and reducing dependence on public welfare programs. At present, there
      is little empirical evidence about the actual effect of vocational interventions
      on economic self-sufficiency or on use of public benefits by persons with mental
      illness. STUDY AIMS: This study provides a preliminary look at how participating
      in supported employment, a form of vocational rehabilitation emphasizing ongoing
      support in competitive jobs, affects the amount that participants earn from work
      and the total amount of income they receive from all sources. Further, we examine
      the extent to which receiving public benefits affects the amount earned from
      private employment, taking into consideration other factors that might be
      associated with benefit status. METHODS: Data are from a randomized trial of
      supported employment interventions. This analysis followed 137 of those study
      participants with severe mental illness for 18 months after they enrolled in
      either of two supported employment programs. Income from various sources was
      estimated based on interviews with study participants upon study entry and at six
      month intervals thereafter. Changes in income from work, government and other
      sources were analyzed using paired Wilcoxon matched-pairs signed-ranks tests and
      t-tests. Using ordinary least-squares regression, we analyzed the effect of
      benefit status on changes in earnings, taking into account diagnosis, work
      history, education, program type, site of program, psychiatric symptoms, global
      functioning and previous earnings. RESULTS: Estimated total income increased by
      an average of $134 (US) per month after enrolling in supported employment. More
      than three-quarters of this increase was from government sources, such as Social
      Security and educational grants. The increase in government income was largely
      due to participants applying for and getting cash benefits for the first time.
      Social Security payments for those receiving benefits before enrollment did not
      change significantly. A small group of persons (n = 22) who did not receive
      Social Security benefits before or after enrolment earned significantly more from
      competitive employment after enrolling than did those who received benefits. This
      finding persisted after taking into acount differences in work history, clinical
      and functional variables and education. LIMITATIONS: Because of the relatively
      small sample size and the lack of continuous measures of income these results
      should be considered preliminary. CONCLUSIONS: Supported employment, one of the
      more effective forms of vocational rehabilitation for persons with mental
      illness, did not reduce dependence on government support. Receiving government
      benefits was associated with lower earnings from work. IMPLICATIONS FOR HEALTH
      CARE PROVISION AND USE: These findings suggest that most persons in treatment for
      severe mental illness need continued public financial support even after
      enrolling in vocational rehabilitation programs. IMPLICATIONS FOR HEALTH POLICY
      FORMULATION: Undoubtedly increased labor force participation can benefit persons
      with mental illness in a number of ways. However, policy makers should be careful
      about justifying increased access to vocational programs on the basis of reduced
      spending for income support. Further, targeting such programs only to persons
      receiving income support may overlook the clients who can benefit most: those who
      are not currently receiving benefits. IMPLICATIONS FOR FURTHER RESEARCH: Policy
      makers need a better understanding of how vocational interventions and income
      support programs affect the income and well-being of persons with mental illness.
      Studies similar to this one should be repeated with larger, more diverse samples
      that will allow use of instrumental variables statistical techniques.

PMID- 11964493
TI  - A partial solution: a local mental health authority for the UK.
AB  - BACKGROUND: the structural problems of the mental health system in the UK have
      been analyzed by a number of authors over the past several years as the "reforms"
      of the health and social service systems have continued (Kavanagh and Knapp,
      1995; Mechanic, 1995). In a recent article, Hadley and Goldman (1995) suggest
      that one possible solution to some of these issues may be the creation of a local
      mental health authority. Such an authority would consolidate the funding,
      authority and responsibility in a single entity. We believe this model, which is
      typical of many local public mental health systems in the US, is at least part of
      the solution to the current problem of financial and service fragmentation of the
      current system in the UK. The numerous "reforms" of the health and social service
      systems (which include the Community Care Act, the development of the Internal
      Market, GP fundholding and the purchaser-provider split) were not designed for
      the care of the mentally ill (Han, 1996). These policy changes in the design of
      health and social services have created a complicated and difficult context in
      which services must be delivered. Too many agencies play a significant role in
      the delivery and management of mental health services. Health authorities, social
      service agencies and GP fundholders are direct and indirect funders of the system
      while community care trusts, social service agencies and GPs are service
      providers (Hadley, 1996a). RESULTS AND A PROPOSAL: We believe that the
      development of local mental health authorities may be part of the solution to the
      structural and economic problems of the current system in the UK. It is not the
      answer to limited resources or limited skills, but can create a new structure,
      which will permit and encourage the cooperation and innovation that is now
      possible only with unusual effort. Local mental health authorities have a number
      of crucial characteristics, but, most importantly, they refocus the system on the
      provision of care to the seriously mentally ill. This is the expressed priority
      of government, advocates and providers, alike.These new entities could be created
      at either the purchaser or provider level or, as exists in a number of
      jurisdictions in the US, at both levels, where a single purchaser may be
      responsible for multiple consolidated providers. This combination is now the
      emerging model for innovative services in the US. In the UK, the development of a
      local mental health authority at the purchaser and/or provider level might be
      relatively simple. Although the creation of a statutory authority would require
      primary legislation and is therefore probably not a short-term solution, there
      appears to be a variety of administrative options that would have the same
      effect. IMPLICATIONS FOR HEALTH POLICY FORMULATION: The creation of a local
      mental health authority may be a necessary first step towards the development of
      a coordinated and comprehensive system of care. It seems likely that there is
      currently more "political" support for the development of a purchaser model but
      the development of a sophisticated purchsaer is also likely to take considerable
      time and effort. Although all the structural and policy problems of the mental
      health system in the UK will not all be solved by local mental health
      authorities, they may be beneficial if responsibility for mental illness care is
      to be centralized and fragmentation is to be reduced. Without making structural
      changes, the best efforts by clinicians, policymakers and managers are most
      likely to be in vain. Without a clear point of ultimate purchasing and service
      responsibility, the fragmentation and inefficiency of the current system will
      remain (Hadley et al., 1996).

PMID- 11964494
TI  - Factors influencing informal care-giving.
AB  - BACKGROUND: As downsizing of institutional care continues, patients discharged
      are likely to have more severe mental illnesses, and to have experienced longer
      tenures within institutions than patients who have been discharged in the past.
      As greater numbers of patients are removed from mental hospitals, the objective
      burden experienced by informal care-givers may increase, particularly if formal
      care levels are inadequate. AIMS OF THE STUDY: This paper documents who assumes
      informal care-giver roles, and the form such care-giving takes for patients
      discharged from a state hospital. Specifically, this paper identifies (i) what
      factors affect a person's decision to assume a care-giver role, including the
      participation of other network members in care-giving, (ii) what factors
      influence whether care-giving is provided in time or in direct purchase of care
      and (iii) how the patient's treatment location affects the decision of the
      network member to assume any care-giving role. DATA AND ANALYTICAL METHODS: Data
      for this paper are taken from a longitudinal study of the closure of a state
      mental hospital in central Indiana. Seventy-seven patients were asked to identify
      their community networks. Ninety-eight network members were surveyed about the
      informal care, both in time or through direct expenditures, they provided to
      these patients one year after discharge. Care-giving relationships were estimated
      using a multivariate probit model. Such a model estimates the extent to which the
      decision to provide care in either form depends on the care-giving activities
      assumed by other network members associated with a given patient, as well as the
      characteristics of individual patients and network members. RESULTS: Forty-one
      per cent of network members provided some level of informal care, with 13.3%
      providing some care in time, and 35.7% providing some care through direct
      expenditures. A positive relationship was found between participation in informal
      care-giving and the perception by the network member that patient needs were not
      being met by professionals. The decision to provide informal care was also found
      to be sensitive to the level of informal and formal care received by the patient.
      Care-giving in expense was found to be positively related to the care-giving
      decisions of other informal care-givers, but care-giving in time was not. Network
      members were more likely to provide care in time for patients who had been
      recently discharged to the community than for patients who remained in
      institutional settings. CONCLUSIONS: These results suggest the transfer of
      persons with severe mental illnesses from state hospitals to the community may
      shift the care burden between formal and informal providers. If this is the case,
      discharge criteria should include such factors as the community resources
      available to the patient. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The
      responsiveness of network members to perceived unmet need bespeaks the importance
      of informal care when the continuity of formal care cannot be assured. Findings
      also suggest there may be some substitution of formal and informal care when
      patients are discharged from institutions. Further analysis is required to
      determine whether network members' perceptions of unmet need are accurate, and
      means by which network members can be made better attuned to unmet needs actually
      experienced by patients.

PMID- 11964495
TI  - Physician knowledge, financial incentives and treatment decisions for depression.
AB  - BACKGROUND: Two important policy levers to affect health care delivery are
      financing and informational interventions. Unfortunately, these two approaches
      have not been considered simultaneously and little is known about how their
      effects compare. AIMS OF THE STUDY: This paper estimates the relative role of
      financial incentives (prepaid versus fee for service) and provider information
      (perceived knowledge of antidepressant medications and skill in counseling for
      depression) on quality of care for less and more severely depressed patients and
      their health and cost outcomes. METHODS: We develop a theoretical model of
      provider behavior and estimate a reduced form using a multinomial probit model
      with heteroskedastic covariances. The likely effects of changing provider
      knowledge about depression treatment in primary care are then simulated and
      contrasted with the effects of a shift toward prepaid managed care as opposed to
      fee-for-service care. The empirical model is estimated using data from the
      Medical Outcomes Study. RESULTS: We conclude that financing and information have
      different effects and that their combination can achieve the conflicting goals of
      improved health outcomes and reduced direct treatment goals. Moreover, including
      family income as one important dimension of social cost suggests that the
      combination of informational interventions and a shift to prepaid care may
      dominate either one intervention in isolation from a social cost perspective.
      Specifically regarding information, we found that increasing provider knowledge
      could have the highly desirable effect of greater targeting of treatments to
      sicker patients while not raising overall treatment rates much - a treatment
      pattern that many hoped managed care could achieve, but for which there has been
      little evidence. CONCLUSIONS: Our analysis illustrates the value of considering
      these widely different policy goals simultaneously. We learned that variation in
      physician knowledge generally had stronger associations with clinically relevant
      practice patterns for depression than did a complete change in financing
      strategy. The moderate change in perceived knowledge we simulated (not near the
      extremes of observed values of perceived knowledge) was associated with enough
      improvement in appropriateness of care to more than offset the reduction in
      appropriateness with a complete shift from fee-for-service to prepaid managed
      care. IMPLICATIONS FOR HEALTH POLICY: The paper demonstrates the importance of
      considering different interventions simultaneously. Combining informational and
      financial interventions simultaneously can achieve better quality of care and
      reduce health care costs, something neither intervention can in isolation.

PMID- 11964496
TI  - Fiber connections of the nucleus isthmi in the carp (Cyprinus carpio) and tilapia
      (Oreochromis niloticus).
AB  - The nucleus pretectalis (NP) is a prominent nucleus in the percomorph pretectum
      and has been shown to project to the nucleus isthmi in the filefish by an HRP
      tract-tracing method [Ito et al., 1981], but a homologous nucleus to the NP is
      apparently lacking in ostariophysans. The present study examined fiber
      connections of the nucleus isthmi in an ostariophysan teleost, the carp
      (Cyprinidae, Cyprinus carpio), to identify a nucleus homologous to the percomorph
      nucleus pretectalis. Identical studies in a percomorph tilapia (Cichlidae,
      Oreochromis niloticus) were also performed. Injections of biotinylated dextran
      amine (BDA) or biocytin to the carp nucleus isthmi labeled cells in the
      ipsilateral optic tectum and nucleus ruber of Goldstein [1905]. Labeled tectal
      neurons were located in the stratum periventriculare (SPV) and the stratum
      fibrosum et griseum superficiale (SFGS). The somata in the SPV were pyriform and
      those in the SFGS were fusiform. No labeled cells were found in the pretectum.
      Labeled terminals were seen in the ipsilateral nucleus pretectalis superficialis
      pars parvocellularis (PSp), optic tectum, and bilateral nucleus ruber. Terminals
      in the nucleus ruber appear to come from tectal neurons in the SFGS labeled by
      isthmic injections. Thus the nucleus isthmi has reciprocal fiber connections with
      the ipsilateral optic tectum, receives projections from the ipsilateral nucleus
      ruber, and projects to the ipsilateral PSp. The nucleus pretectalis homologue is
      apparently absent in the carp. Studies in tilapia showed that the nucleus isthmi
      receives bilateral projections from the NP and optic tectum. In addition, the
      present study revealed a previously unknown afferent from the nucleus ruber to
      the percomorph nucleus isthmi. The tilapia nucleus isthmi projects to the same
      targets as in the carp. Isthmic projection neurons in the tilapia optic tectum
      were located in the SPV and pyriform with a similar shape to the carp SPV neurons
      that project to the nucleus isthmi. No labeled cells were found in the SFGS of
      tilapia optic tectum. The fusiform neurons in the SFGS of the carp optic tectum
      possess various hodological similarities with the NP and may correspond to the NP
      neurons of percomorphs.

PMID- 11964497
TI  - The vestibular nuclei and vestibuloreticular connections in the mallard (Anas
      platyrhynchos L.). An anterograde and retrograde tracing study.
AB  - The vestibular apparatus provides information about the position and movements of
      the head. Craniocervical muscles position the head with respect to the upper part
      of the neck. Motoneurons innervating these muscles are located in the supraspinal
      nucleus and ventral horn of the rostral cervical cord. Premotor neurons of
      craniocervical muscles have been found in the medial two-thirds of the medullary
      reticular formation: the ventromedial part of the parvocellular reticular
      formation and the gigantocellular reticular formation. In the present study,
      projections from vestibular nuclei upon craniocervical premotor neurons were
      investigated using anterograde and retrograde tracers. Vestibulospinal fibers run
      bilaterally in the medial vestibulospinal tract and ipsilaterally in the lateral
      vestibulospinal tract. Vestibuloreticular projections are mainly ipsilateral, and
      originate from the n. vestibularis lateralis pars ventralis and pars dorsalis,
      and from the n. vestibularis descendens. Terminal labeling is found in the border
      zone between the parvocellular and gigantocellular reticular formation. These
      projections show that in addition to direct bilateral vestibulo-craniocervical
      projections an indirect vestibular pathway to craniocervical motor nuclei exists.
      The direct pathway probably is the neural substrate for the vestibulocollic
      reflex, whereas the vestibular projection upon the reticular formation might
      influence head orientation during various kinds of activities, such as pecking,
      preening and so on.

PMID- 11964498
TI  - Exploitation of an ancient escape circuit by an avian predator: relationships
      between taxon-specific prey escape circuits and the sensitivity to visual cues
      from the predator.
AB  - The painted redstart Myioborus pictus uses visual displays to flush, pursue, and
      then capture an abundance of brachyceran Diptera that are equipped with giant
      fiber escape circuits. This paper investigates the relationships between features
      of the giant fiber system, the structure of visual stimuli produced by redstarts
      and their effectiveness in eliciting escape reactions by flies. The results show
      that dipterous taxa having large-diameter giant fibers extending short distances
      from the brain to motor neurons involved in escape are flushed at greater
      distances than taxa with longer and small-diameter giant fibers. The results of
      behavioral tests show the importance of angular acceleration of expanding image
      edges on the compound eye in eliciting escape responses. Lateral motion of
      stimulus profile edges as well as structured visual profiles additionally
      contribute to the sensitivity of one or more neural systems that trigger escape.
      Retinal subtense and angular velocity are known to trigger physiological
      responses in fly giant fiber circuits, but the contributions of edge length and
      lateral motion in a looming stimulus suggest that escape pathways might also
      receive inputs from circuits that are tuned to different types of motion. The
      present results suggest that these several properties of escape pathways have
      contributed to the evolution of foraging displays and plumage patterns in flush
      pursuing birds.

PMID- 11964499
TI  - Cytogenetic arguments in favour of a taxonomic revision of Lepilemur
      septentrionalis.
AB  - Cytogenetic investigations performed on 30 specimens of Lepilemur septentrionalis
      confirmed the existence of 4 karyotypes differing from each other by 1-2
      chromosomal rearrangements. These data, pooled with those obtained in earlier
      studies, showed that out of 60 animals karyotyped only two kinds of hybrids were
      detected, allowing us to characterise two chromosomally polymorphic populations.
      No natural hybrids could be found between these two populations, which could thus
      be considered as two separate species. The possible role of the chromosomal
      rearrangements in the process of reproductive isolation between these two
      populations is discussed.

PMID- 11964500
TI  - Earliest record of a parapithecid anthropoid from the Jebel Qatrani formation,
      Northern Egypt.
AB  - A fifth anthropoid (= anthropoidean, simian or simiiform) genus and species from
      the late Eocene Fayum Quarry L-41, Abuqatrania basiodontos gen. et sp. nov.,
      further augments the already remarkable primate diversity from this locality and
      provides the first convincing extension of the enigmatic family Parapithecidae
      into the oldest productive vertebrate fossil-bearing stratum of the Jebel Qatrani
      Formation. A. basiodontos exhibits no clear autapomorphies nor any apomorphies
      that are shared exclusively with any other parapithecid species, and it is most
      parsimoniously interpreted as the sister taxon of a Qatrania-Parapithecus-Apidium
      clade. Reevaluation of two contemporaries of A. basiodontos, Serapia and
      Arsinoea, suggests that neither genus should be ranked as a basal parapithecid.
      Serapia is more derived than primitive parapithecids in the morphology of the
      lower fourth premolar and exhibits greater overall similarity to Proteopithecus
      in cusp placement and the shape and proportions of its lower teeth; accordingly,
      we place Serapia in the family Proteopithecidae. Arsinoea is much more
      problematic and does not fit well with any hitherto known Afro-Arabian anthropoid
      group; we place this genus in a new anthropoid family, Arsinoeidae.

PMID- 11964501
TI  - Social anti-predator behaviour in a nocturnal lemur.

PMID- 11964502
TI  - Diet of northern masked titi monkeys (Callicebus personatus).

PMID- 11964503
TI  - Geophagy amongst Formosan macaques at Mount Longevity, Taiwan.

PMID- 11964506
TI  - Abstracts of the First Meeting of the Asociacion Primatologica Espanola (APE) and
      First European Workshop on Primate Research. Madrid, October 16-19, 1996.

PMID- 11964507
TI  - [Physicians in the nets of industry?].

PMID- 11964504
TI  - Ancient DNA from Megaladapis edwardsi.

PMID- 11964508
TI  - [Communication competence in ultrasound examination in pregnancy].
AB  - INTRODUCTION: 293 physicians in the German-speaking part of Switzerland were
      questioned about their practices of providing information during prenatal
      ultrasound examinations. Physicians were asked both how they provide information
      about the examination procedure itself as well as how they inform the pregnant
      woman if a fetal anomaly is detected. METHOD: In January 2000, a questionnaire
      was mailed to a sample of 500 physicians with a specialized qualification in
      pregnancy ultrasound examinations. The response rate was 59.2%. RESULTS: 90.1% of
      the physicians reported that they offer information consultations for routine
      ultrasound examinations. 50.2% mentioned in their answers to an open question
      that the screening for fetal anomalies is a component of their consultation.
      Female physicians mentioned this aspect significantly more often than male
      physicians. Regarding difficulties in the communication of a diagnosis of fetal
      malformation, the physicians reported most frequently the excessive strain on the
      pregnant woman, but also their own feelings of helplessness. The subjective
      emotional stress was considered as high; female physicians with experience of
      motherhood reported the highest levels of stress. CONCLUSIONS: Screening for
      fetal anomalies is a difficult and often neglected subject when providing
      information on prenatal ultrasound examinations. The communication of the
      diagnosis of a fetal anomaly is not only emotionally stressful for the parents,
      but also for the physicians and requires high levels of communication competence.
      These communication aspects should be considered in the training for ultrasound
      examinations during pregnancy.

PMID- 11964509
TI  - [Psychosocial and psychosomatic basic competence of the gynecologist--from
      intrinsic conviction to a learnable curriculum. (2. Biosychosocial model and
      basic psychiatric therapy].
AB  - Besides the communicative skills and medical interviewing techniques (part 1 in
      Gynakol Geburtshilfliche Rundsch 2001;41:158-165), it is the biopsychosocial
      model of health and disease which constitutes the second important element of the
      basic psychosomatic and psychosocial competence of the gynecologist. According to
      this model biological-somatic and psychosocial factors are concomitantly and
      equally taken into account during the diagnostic and therapeutic process. To
      conceptualize the possible pathology of psychosocial factors, the following
      categories have proven helpful in everyday work: behavior, stress, conflicts and
      developmental defects and disturbances. These categories are not objectively
      measurable, but they are accessible for the gynecologist in the consultation by
      means of the three following functions: assessment and monitoring of the
      patient's problems (somatic, psychological, social) by patient-centered
      communication; establishment, maintenance and termination of a therapeutic
      helpful relationship by perception of and response to emotions; development of a
      problem-solving plan and help for its realization by means of information giving
      and influencing behavioral changes.

PMID- 11964510
TI  - [Comment on "Psychosocial and psychosomatic basic competence of the gynecologist-
      from intrinsic conviction to a learnable curriculum". 1: Communication. 2:
      Biopsychosocial model and psychiatric basic management].

PMID- 11964511
TI  - [Ovarian tuberculosis].
AB  - Although the tuberculosis rate in Germany and in the Western industrialized
      nations is stable, it is still one of the most significant infectious diseases
      worldwide. Immigrants and asylum seekers make up a large proportion of new cases,
      and with 15%, the occurrence of multidrug-resistant tuberculosis patients from
      the former Soviet Union is above average. This study, describing a patient with
      ovarian tuberculosis, undertakes a classification of risk groups as well as
      presents the potential differential diagnosis and its limitations.

PMID- 11964512
TI  - [Presence of the SSGO and its members in the internet. Recommendations of the
      commission for quality control of the Swiss Society of Gynecology and
      Obstetrics].
AB  - When setting up and running websites for medical practices and clinics, the costs
      and the requirements with regard to the know-how can necessitate collaboration
      with industrial providers. This can lead to financial involvement which requires
      regulation. Publicity is not recommended, although today it is no longer
      forbidden; links to other websites are allowed, but only for passing on
      addresses; the use of third-party material in connection with the homepage must
      be disclosed; medical information must be written by medical professionals. In
      the setting-up and running of websites for medical practices and clinics, it is
      recommended to adopt the HON code and to avoid any additional professional
      certification.

PMID- 11964513
TI  - [Recommendations for oral contraception. 26th Meeting of the "Zurich Discussion
      Circle" March 2001].

PMID- 11964514
TI  - [Introduction to long-term contraception. Recommendations of the Austrian-Swiss
      Working Group. Psychological aspects of long-term contraception].

PMID- 11964515
TI  - [Long-term contraception. Recommendations of an Austrian-Swiss Working Group].

PMID- 11964516
TI  - [Comment on the editorial. Stem cells from placental blood].

PMID- 11964518
TI  - Age-dependent changes in 24-hour rhythms of thymic and circulating growth hormone
      and adrenocorticotropin in rats injected with Freund's adjuvant.
AB  - OBJECTIVE: To analyze the 24-hour changes in thymic and serum concentration of
      growth hormone (GH) and adrenocorticotropin (ACTH) and their correlation with
      thymic concentrations of glutamate, aspartate, taurine and GABA in young and old
      rats during the acute phase of adjuvant's arthritis. METHODS: Young (50-day-old)
      and old (18-month-old) rats were injected subcutaneously with Freund's adjuvant
      or its vehicle (paraffin oil containing 15% mannide monooleate). Eighteen days
      later, they were killed at six different time intervals throughout a 24-hour
      cycle. Serum and thymic levels of GH and ACTH were measured by radioimmunoassay.
      Thymic amino acid concentration was measured by HPLC. A quantitative assessment
      of arthritis was made in an independent group of rats by plethysmography.
      RESULTS: Old rats injected with Freund's adjuvant exhibited fewer clinical signs
      of inflammation than young rats. Significant 24-hour changes in thymic and serum
      GH occurred, except for serum GH in adjuvant's vehicle-treated old rats. Aging
      augmented thymic GH and decreased serum GH. Immunization with Freund's adjuvant
      did not modify GH concentration. Thymic and serum concentration of GH correlated
      negatively. Thymic ACTH varied significantly over 24 h with maxima during the
      dark phase, except in Freund's adjuvant-treated young rats. Maximal serum ACTH
      levels occurred in the late afternoon except in Freund's adjuvant-treated old
      rats which showed maxima at night. Immunization with Freund's adjuvant augmented
      thymic and circulating concentrations of ACTH. Thymic and serum concentration of
      ACTH correlated positively. Thymic concentration of glutamate, aspartate and
      taurine decreased in aged rats and correlated significantly with thymic ACTH.
      CONCLUSION: The results support the existence of a thymic compartment of GH and
      ACTH that may be independently regulated.

PMID- 11964519
TI  - Neuroimmune interactions in experimental colitis. An immunoelectron microscopic
      study.
AB  - With its abundance of neurons and immunocytes, the gut is a potentially important
      site for the study of the interaction between the nervous and immune systems. In
      this electron microscopic study we have investigated the distribution of
      substance P (SP)- and vasoactive intestinal polypeptide (VIP)-immunoreactive (IR)
      nerve terminals and the immunocytes during experimental colitis in the rat. A
      mild colitis was induced by a luminal enema containing trinitrobenzene sulfonic
      acid. The most severe inflammation was detected after 2 days and the density and
      the distribution of the SP- and VIP-IR nerve terminals as well as the
      immunocompetent cells were studied at that time. Many SP- and VIP-IR nerve
      terminals were observed in a very close situation to the inflammatory cells. The
      number of VIP-IR nerve terminals slightly increased in the inflamed area. The gap
      between the axolemma of the nerve terminals and immunocytes was 20-200 nm. Some
      lymphocytes and plasma cells were also IR for SP in the inflamed area, whereas no
      IR immunocytes were observed in the control and in noninflamed area from the same
      animal. The very close apposition of the SP- and VIP-IR nerve terminals to the
      inflammatory cells as well as the presence of SP-IR immunocytes in inflamed area
      support the suggestion that bidirectional neuroimmunomodulation exists in the
      colon.

PMID- 11964520
TI  - Growth hormone prevents Fas-induced apoptosis in lymphocytes through modulation
      of Bcl-2 and caspase-3.
AB  - OBJECTIVE: Growth hormone (GH) has been reported to have a potent effect on the
      immune system. However, the detailed mechanism of the effect of GH on the immune
      system has not yet been clarified. This study was designed to investigate the
      nature of this mechanism. METHODS: In the present study, we investigated the
      effects of GH on the susceptibility of both human CEM/C7 lymphocytes and human IM
      9 lymphocytes to Fas-induced apoptosis. RESULTS: Both cell lines expressed GH
      receptor mRNA. GH rescued Fas-induced suppression of [(3)H]-thymidine
      incorporation into each cell line. GH prevented Fas-induced apoptosis in each
      cell line without changing Fas antigen expression. We next investigated the
      mechanisms of the prevention of Fas-induced apoptosis, by focusing on
      intracellular molecules related to the apoptotic signal. Bcl-2 expression was
      increased by GH treatment in both CEM/C7 and IM-9 lymphocytes. GH also
      downregulated caspase-3 expression and inhibited activation of caspase-3 in both
      cell lines. CONCLUSION: These findings suggest that GH regulates the human immune
      system through inhibition of Fas-induced apoptosis in activated T and B
      lymphocytes.

PMID- 11964521
TI  - Differential inhibition by nimesulide of the early and late phases of intravenous
      and intracerebroventricular-LPS-induced fever in guinea pigs.
AB  - OBJECTIVES: The findings that inducible cyclooxygenase (COX)-2, but not
      constitutive COX-1, is upregulated in the brain of conscious rats approximately
      1.5 h after intraperitoneal pyrogen administration, that the systemic
      administration of COX-2 inhibitors abolishes fever, and that COX-2-deficient mice
      do not develop fever in response to intraperitoneal lipopolysaccharide (LPS) have
      strongly implicated COX-2 in the mediation of the febrile response. However, the
      biosynthesis of COX-2 is significantly slower than the onset of the fever
      produced by intravenously injected LPS. It consequently seems improbable that
      inducible COX-2 could play a role in the initiation of this febrile response, but
      a role for COX-1 has not yet been categorically ruled out; or, alternatively, a
      constitutive isoform of COX-2 could have such a role. We have studied, therefore,
      the effects of the non-selective COX inhibitor indomethacin, the COX-1-selective
      inhibitor SC-560, and the COX-2-selective inhibitor nimesulide on the
      characteristically biphasic fever induced by intravenous LPS in conscious guinea
      pigs; it has an onset latency of approximately 10 min. METHODS: We injected the
      inhibitors 30 min before LPS, in various combinations of doses and routes; their
      respective vehicles were the control solutions. Core temperatures (T(c)) were
      monitored continuously, and plasma and brain PGE(2) levels were measured before
      and at 2-hour intervals after LPS administration. RESULTS: Intraperitoneal
      indomethacin at 10 mg kg(-1) attenuated both phases of intravenous LPS (2 microg
      kg(-1)) fever, but the first more so than the second; at 50 mg kg(-1), it
      inhibited the febrile response completely. Intraperitoneal SC-560 (5 mg kg(-1))
      did not affect the febrile response to intravenous LPS (2 microg kg(-1)).
      Intraperitoneal nimesulide (0.3, 1.0, and 3.0 mg kg(-1)) dose dependently
      attenuated intravenous LPS (0.1 and 2 microg kg(-1)) fever; the second phase of
      the biphasic T(c) rise was affected significantly more than the first.
      Intraperitoneal nimesulide also prevented the associated rises in plasma and
      brain PGE(2) levels. Intracerebroventricular LPS (150 ng kg(-1)) evoked a
      monophasic fever with a long onset latency ( approximately 30 min); it was
      accompanied by a rise in brain PGE(2) only, implying that the febrigenic PGE(2)
      was generated directly in the brain. This response, however, was completely
      abolished by intraperitoneal nimesulide (3 mg kg(-1)), indicating that nimesulide
      crosses the blood-brain barrier. Intracerebroventricular nimesulide at 0.3 mg kg(
      1) prevented the rise in plasma PGE(2) after intravenous LPS (2 microg kg(-1))
      and again attenuated the second febrile peak significantly more than the first.
      CONCLUSIONS: COX-1 is not involved in intravenous LPS fever production, and COX-2
      appears to play a greater role in the late than in the early phase of intravenous
      LPS fever in guinea pigs. The involvement of a constitutive COX-2 is inferred in
      the early phase.

PMID- 11964522
TI  - Effects of aminoguanidine and meloxicam on nitric oxide and prostaglandin E
      production induced by lipopolysaccharide in the hypothalamus and anterior
      pituitary of the rat.
AB  - BACKGROUND/OBJECTIVE: Injection of bacterial lipopolysaccharide (LPS) into male
      rats activates genes that in turn induce many enzymes that participate in the
      animals' response to LPS. There is induction of inducible nitric oxide synthase
      (iNOS) and cyclooxygenase 2 (COX-2) in many tissues. This induction could result
      from combination with cell surface LPS receptors that directly induce both genes,
      or the nitric oxide (NO) released as a result of iNOS induction could induce COX
      2. METHODS: To distinguish between these two possibilities, specific inhibitors
      of iNOS and COX-2 activity, aminoguanidine (AG) and meloxicam (MLX),
      respectively, were injected either peripherally or intracerebroventricularly
      (i.c.v.), and their effect on NO and prostaglandin E (PGE) production induced by
      LPS in the medial basal hypothalamus (MBH) and anterior pituitary gland (AP) were
      determined. RESULTS: Peripheral injection of AG blocked iNOS-derived NO
      production in the AP but not in the MBH. When AG was injected i.c.v., iNOS
      derived NO production in the MBH was blocked. MLX injected peripherally blocked
      COX-2-derived PGE(2) production in the MBH and AP, whereas AG injected
      peripherally or i.c.v. was ineffective. Since AG was only effective in blocking
      iNOS-derived NO production in the MBH when injected i.c.v., AG apparently does
      not effectively cross the blood brain barrier, whereas MLX injected peripherally
      inhibited PGE production, probably by inhibiting COX-2 activity in both the MBH
      and AP. AG was ineffective in preventing the increase in PGE derived from COX-2
      in either the MBH or AP. CONCLUSION: LPS directly induces both enzymes, iNOS and
      COX-2, in the hypothalamus and AP.

PMID- 11964523
TI  - Hypothalamic digoxin, hemispheric dominance and the acquired immunodeficiency
      syndrome.
AB  - OBJECTIVES: Hypothalamic digoxin, an isoprenoidal metabolite, is an endogenous
      regulator of membrane Na(+)-K(+) ATPase activity, immune activation and synaptic
      neurotransmission. The objective of this study was to assess the role of
      hypothalamic digoxin and hemispheric dominance in the pathogenesis of the
      acquired immunodeficiency syndrome (AIDS) and in the genesis of sexual
      orientation. METHODS: The isoprenoid-pathway-related cascade - (i) isoprenoidal
      metabolites - digoxin, dolichol and ubiquinone, (ii) tryptophan/tyrosine
      catabolic patterns, (iii) glycoconjugate metabolism, (iv) free radical metabolism
      and (v) membrane composition were assessed in AIDS (CDC stage - group IV -
      subgroup C), individuals with differing hemispheric dominance as well as in
      individuals with differing sexual orientation. Statistical analysis was done by
      Student's t test with modified degrees of freedom. RESULTS: The HMG CoA reductase
      activity was increased with increased digoxin and dolichol levels and reduced
      ubiquinone levels in AIDS. The membrane Na(+)-K(+) ATPase activity and serum
      magnesium levels were reduced. The tryptophan catabolites (serotonin, quinolinic
      acid, nicotine and strychnine) were increased and the tyrosine catabolites
      (morphine, dopamine and noradrenaline) were reduced. The serum glycoconjugate
      metabolites were increased and lysosomal stability was reduced in AIDS. There was
      reduced incorporation of glycoconjugates into membranes and an increased membrane
      cholesterol:phospholipid ratio. Lipid peroxidation products and NO were increased
      while free radical scavenging enzymes and reduced glutathione were reduced. The
      biochemical patterns obtained in AIDS correlated with those obtained in right
      hemispheric dominance and homosexuals/bisexual states. CONCLUSIONS: Hypothalamic
      digoxin and right-hemispheric dominance is important in the predisposition to
      AIDS as well as homosexual/bisexual states.

PMID- 11964524
TI  - Accumulation of DC-SIGN+CD40+ dendritic cells with reduced CD80 and CD86
      expression in lymphoid tissue during acute HIV-1 infection.
AB  - BACKGROUND: Dendritic cells (DC) are target cells for HIV-1 and play a key role
      in antigen presentation and activation of T cells. OBJECTIVE: To characterize
      interdigitating DC in lymphoid tissue (LT) with regard to maturation, expression
      of cytokines and co-stimulatory molecules in HIV-1-positive patients. METHODS: DC
      were characterized by immunohistochemistry and in situ imaging in LT from
      patients with acute HIV-1 infection (aHI), antiretroviral treated patients, long
      term non-progressors/slow progressors with HIV-1 infection (LTNP/SLP), patients
      with AIDS, HIV-1-negative controls and patients with acute Epstein-Barr virus
      (EBV) infection. RESULTS: A significant increase of interdigitating DC expressing
      CD1a, S-100b, CD83 and DC-SIGN was found in LT from patients with aHI (P < 0.02).
      The co-stimulatory molecules CD80 and CD86 were, however, only partially
      upregulated and the complete parafollicular network found in acute EBV infection
      was not generated, despite increased expression of interleukins 1alpha, 1beta,
      12; interleukin 1alpha receptor antagonist; interferon alpha; and CD40
      expression. LTNP/SLP and treated aviremic subjects had increased frequency of
      interdigitating DC, albeit lower than in aHI, and low expression of CD80 and
      CD86. In contrast, patients with AIDS had fewer DC and reduced cytokine
      expression in LT. CONCLUSIONS: In the early phase of HIV-1 infection, there was a
      migration of DC to LT comparable to that found in acute EBV infection. The
      infiltration of DC in LT in acute EBV infection was accompanied by upregulation
      of CD80 and CD86 expression, which did not occur in aHI. This co-stimulatory
      defect in aHI may have an impact on the development of HIV-1-specific T cell
      immunity.

PMID- 11964526
TI  - Cytotoxic T-cell recognition of HIV-1 cross-clade and clade-specific epitopes in
      HIV-1-infected Thai and Japanese patients.
AB  - OBJECTIVE: To identify and characterize cytotoxic T-cell (CTL) epitopes for HIV-1
      clade E using eight known HLA-A*1101-restricted HIV-1 clade B epitopes. METHODS:
      Induction of clade E-specific CTL was examined by stimulating peripheral blood
      mononuclear cells (PBMC) from clade E-infected Thai individuals with the clade E
      specific peptide corresponding to the clade B epitopes. Cross-clade and clade
      specific CTL recognition for these epitopes was analysed using CTL clones and
      bulk CTL specific for these epitopes. To clarify the presentation of these
      epitopes in HIV-1-infected T cells, CTL recognition for the clade E-specific and
      cross-clade epitopes was investigated using CD4CXCR4 cells infected with an HIV-1
      clade E clone. RESULTS: Three epitopes, which are identical among clades A-E,
      were recognized as cross-clade CTL epitopes in both individuals. Clade B and E
      sequences corresponding to three epitopes were recognized as clade-specific
      epitopes in clade B-infected and clade E-infected individuals, respectively. In
      contrast, clade E-specific peptides corresponding to two other clade B epitopes
      failed to elicit clade E-specific CTL. CTL specific for the three cross-clade and
      three clade E-specific epitopes effectively lysed target cells infected with HIV
      1 clade E virus. CONCLUSIONS: These six epitopes are found to be processed
      naturally in HIV-1 clade E-infected cells. We show here that a strategy utilizing
      HIV-1 clade B epitopes is very useful for identifying clade E CTL epitopes.

PMID- 11964525
TI  - The human 26S proteasome is a target of antiretroviral agents.
AB  - BACKGROUND: Proteasomes constitute the degradative machinery of the
      ubiquitin/adenosine triphosphate-dependent proteolytic pathway, which is involved
      in many cell functions, including immune response and apoptosis, and in HIV
      maturation and infectivity. OBJECTIVE: To examine whether proteasomes are
      targeted by antiretroviral agents. METHODS: Chymotrypsin-like, trypsin-like and
      peptidyl-glutamyl-peptide hydrolysing activities of purified human 26S and 20S
      proteasomes, the latter depleted or enriched in 11S regulator, were assayed after
      incubation with indinavir, lamivudine and zidovudine at 1-80 microM alone and in
      combination. To assess the drug effects on cellular functions regulated by
      proteasomes, the accumulation of ubiquitin-tagged proteins, the processing of the
      nuclear factor kappa B precursor p105, and the degradation of the inhibitor of
      nuclear factor kappa B, isoform alpha (IkappaBalpha) were evaluated by Western
      immunoblotting in Jurkat cells after incubation for 6 h with the drugs above.
      RESULTS: Trypsin-like and mostly chymotrypsin-like activities of purified 26S
      proteasome were inhibited by each drug from 10 to 80 microM, more by double
      combinations and mostly by the triple combination. The peptidyl-glutamyl-peptide
      hydrolysing activity of the 26S proteasome and the three peptidase activities of
      the 20S proteasome, depleted or enriched in 11S regulator, were unaffected. The
      accumulation of ubiquitin-tagged proteins, reduced IkappaBalpha degradation and
      p105 processing were appreciable in intact cells with the triple drug
      combination. CONCLUSION: The human 26S proteasome is a target of antiretroviral
      agents. This suggests that the antiviral action and some clinical and
      immunological benefits of combined antiretroviral therapy rely not only on its
      known effects on viral enzymes, but also on host cell components.

PMID- 11964527
TI  - Strong CD4 Th1 responses to HIV and hepatitis C virus in HIV-infected long-term
      non-progressors co-infected with hepatitis C virus.
AB  - OBJECTIVES: To compare the T-cell responses to hepatitis C virus (HCV) and HIV in
      HIV-infected long-term non-progressors (LT-NP) and HIV-positive progressors co
      infected with HCV and in HIV-negative HCV-infected patients. METHODS: Three
      groups were studied: 10 HCV/HIV-infected LT-NP, 26 HCV/HIV-infected progressors
      and 13 HCV-infected/HIV-negative patients. Virus-specific CD4 and CD8 T-cell
      responses in peripheral blood were assessed by interferon (IFN)-gamma Elispot
      assays using recombinant proteins (HIV-p24 and three HCV antigens) and 16 HIV or
      HCV HLA A3- and/or HLA A2-restricted cytotoxic T lymphocytes peptides.
      Statistical analysis was performed with non-parametric tests. RESULTS: In
      addition to high T helper 1 (Th1) cell frequencies directed against HIV-p24, LT
      NP had significantly (P < 0.05) higher frequencies of Th1 cells against HCV than
      the two other groups. No difference was observed between HIV-infected progressors
      and HIV-negative controls. Furthermore, HCV-specific CD4 and CD8 T cells were
      correlated in LT-NP (P = 0.006). CONCLUSION: Thus, independently of the HIV
      related immune alterations, LT-NP of the HIV-infection might have an intrinsic
      capacity to develop strong Th1 cell responses to viruses, particularly HIV and
      HCV.

PMID- 11964528
TI  - Improved long-term suppression of HIV-1 replication with a triple-class multidrug
      regimen compared with standard of care antiretroviral therapy.
AB  - BACKGROUND: The treatment of HIV-1-infected patients with triple-drug combination
      therapy results in profound suppression of viral replication. In most therapy
      naive patients plasma HIV-1-RNA levels (pVL) drop below the lower limit of
      quantification (LLQ) of currently used assays. In a large percentage of such
      patients, more sensitive assays provide evidence of residual viral replication.
      The question is whether more potent therapy can further suppress this residual
      replication. METHODS: Thirty control patients who, using very strict criteria,
      had not experienced virological failure during 3 years of standard therapy, were
      compared with 10 patients treated with a five-drug regimen, consisting of three
      different classes of antiretroviral drugs (alternative multidrug regimen). A
      modified ultrasensitive assay with an LLQ of 5 copies/ml was used to re-test
      plasma obtained at week 48 and at three timepoints at and around week 144.
      RESULTS: At weeks 48 and 144 pVL could be quantified significantly more
      frequently in control patients than in patients using the alternative multidrug
      regimen (week 48: 42 versus 0% with quantifiable pVL, P = 0.017; week 144: 60
      versus 14% with at least one quantifiable pVL, P = 0.036, respectively). A low
      baseline CD4T cell count was predictive of quantifiable pVL in control patients,
      but not in alternative multidrug patients. CONCLUSION: This proof-of-principle
      study demonstrates that the use of an alternative multidrug regimen results in
      stronger long-term suppression of pVL compared with clinically successful
      treatment with standard therapy.

PMID- 11964529
TI  - Phenotypic or genotypic resistance testing for choosing antiretroviral therapy
      after treatment failure: a randomized trial.
AB  - OBJECTIVE: To assess the respective value of phenotype versus genotype versus
      standard of care for choosing antiretroviral therapy in patients failing protease
      inhibitor-containing regimens. METHODS: Patients with plasma HIV-1 RNA exceeding
      1000 copies/ml were randomly allocated to phenotyping, genotyping, or standard of
      care. RESULTS: Five-hundred and forty-one patients were randomized, 190 to
      phenotyping, 192 to genotyping and 159 to standard of care. The baseline median
      CD4 cell count (280 x 106 cells/l), the plasma HIV-1 RNA level (4.3 log10
      copies/ml), and the number of drugs previously received (n = 6) were similar in
      the three arms. More patients in the standard-of-care arm received at least three
      new drugs (55% versus 20% in the other arms; P < 0.001) and a regimen containing
      drugs from the three different classes. Plasma HIV-1 RNA was < 200 copies/ml at
      week 12 in 35% of patients in the phenotyping arm, 44% in the genotyping arm and
      36% in the standard-of-care arm (phenotyping versus standard of care, P = 0.918;
      genotyping versus standard of care, P = 0.120). In a secondary analysis of 179
      patients experiencing a first protease inhibitor failure, the percentage of
      patients achieving HIV-1 RNA < 200 copies/ml was significantly higher in the
      genotyping arm (65%) than in the phenotyping (45%) and the standard-of-care arms
      (45%) (genotyping versus standard of care, P = 0.022). CONCLUSIONS: Overall,
      resistance assays did not demonstrate benefit over standard of care. In patients
      with the most limited protease inhibitor experience, a significant benefit was
      observed in the genotyping arm.

PMID- 11964530
TI  - Determinants of recurrent toxicity-driven switches of highly active
      antiretroviral therapy. The ATHENA cohort.
AB  - BACKGROUND: Toxicity is the most important reason for premature switching of
      highly active antiretroviral therapy (HAART). In order to optimize the benefit
      risk ratio of HAART, guidelines for toxicity management are needed. OBJECTIVE: An
      observational cohort study to estimate the incidence and identify determinants of
      toxicity-driven switches on second-line HAART after having switched first-line
      HAART despite successful viral suppression. METHODS: Patients were selected from
      those in the ATHENA cohort (n = 2470) who switched the initial HIV protease
      inhibitor (PI)-containing HAART while plasma HIV-1 RNA was <or= 500 copies/ml (n
      = 775). One-year cumulative incidences of subsequent toxicity-driven switches and
      adjusted relative risks (RR) for potential determinants were calculated. RESULTS:
      The 1-year cumulative incidence of toxicity-driven switches of the second regimen
      was 24% [95% confidence interval (CI), 21-28], mostly because of gastrointestinal
      toxicity and neuropathy. Those who had switched from first HAART because of
      toxicity were at an increased risk of a recurrent toxicity-driven switch (RR,
      2.5; 95% CI, 1.7-3.5). Switching from PI to nevirapine while continuing the other
      antiretroviral drugs was more protective against a subsequent switch because of
      further toxicity than changing to another PI-containing regimen (RR, 0.2; 95% CI,
      0.1-0.6). CONCLUSIONS: As for first-line HAART, toxicity is responsible for the
      majority of switches during second-line HAART. Prior switching for toxicity
      increased the risk of having to switch the subsequent regimen for toxicity, but
      this risk is reduced when switching to nevirapine rather than to an alternative
      PI. The latter should be taken into account when designing toxicity-management
      guidelines.

PMID- 11964531
TI  - Impact of occasional short interruptions of HAART on the progression of HIV
      infection: results from a cohort study.
AB  - OBJECTIVES AND DESIGN: To investigate the clinical consequences of occasional and
      short (<or= 3 months) treatment interruptions in patients having initiated highly
      active antiretroviral therapy (HAART). Data from the prospective Swiss HIV Cohort
      Study were used. METHODS: Four different endpoints [death, Centers for Disease
      Control and Prevention (CDC) stages B and C, and CD4 cell count increase >or= 50
      x 106/l] were studied in relation to the number of interruptions that occurred.
      In order to focus on short interruptions exclusively, observations of patients
      with a treatment interruption of > 3 months were censored. The CD4 cell count and
      viraemia were treated as time-dependent variables because of the importance of
      these factors when an interruption occurs. RESULTS: Between 1 January 1996 and 31
      October 2000, 4720 Swiss HIV Cohort Study participants initiated HAART, which was
      interrupted at least once by 1299 participants. The main reasons for the
      interruptions were social factors. Interruptions did not increase significantly
      the risk of HIV-associated morbidity and mortality, except for a marginally
      increased risk for a CDC stage C event after the first interruption. The first
      interruption decreased significantly the likelihood of increasing the CD4 cell
      count. Subsequent interruptions had no further significant effect. High CD4 cell
      count and low viraemia, assessed as baseline and as longitudinal variables, were
      associated with a decreased risk of clinical progression. CONCLUSIONS: Occasional
      treatment interruptions of < 3 months neither worsen nor improve disease outcome
      on an average term (3-4 years). Our results suggest that interruptions might be
      non-risky, particularly when viraemia is low and CD4 cell count is high. These
      results require confirmation.

PMID- 11964532
TI  - Use of filgrastim as adjuvant therapy in patients with AIDS-related
      cytomegalovirus retinitis.
AB  - BACKGROUND: Neutropenia in AIDS predisposes to bacterial infection. Granulocyte
      colony-stimulating factor (filgrastim) can reverse neutropenia. OBJECTIVE: To
      determine the effects of filgrastim on bacterial infections, hospitalization, and
      mortality in patients with cytomegalovirus retinitis and AIDS. METHODS: Using a
      person-time analysis, a retrospective cohort study of filgrastim adjuvant therapy
      in three multicenter clinical trials of anti-cytomegalovirus therapy during the
      period 1990-1997 measured filgrastim use, bacterial infections, and mortality.
      RESULTS: Of 719 patients, 379 patients used filgrastim for 31% of the follow-up
      time. There was an inverse relationship between the 389 confirmed bacterial
      infections, including 186 bacteremias, and absolute neutrophil counts. Before
      adjustment for CD4 T-cells counts and antibiotic/antiretroviral therapy,
      filgrastim was associated with reduced risk of catheter-related bacteremia
      [relative risk (RR), 0.52; P = 0.02] and repeat bacterial infection (RR, 0.41; P
      = < 0.01). After adjustment, the RR of catheter-related bacteremia with
      filgrastim use was decreased (RRadj, 0.69; P = 0.16) and the RR of repeat
      bacterial infection with filgrastim use was of marginal significance (RRadj,
      0.57; P = 0.07), possibly due to the confounding effect of trimethoprim
      sulfamethoxazole on all bacteremia (RRadj, 0.55; P = < 0.01). Unrelated to
      bacteremia, filgrastim use was associated with a 56% reduction in mortality (P <
      0.01). CONCLUSIONS: There was a large survival benefit associated with filgrastim
      use in this study but the reasons for this benefit are unclear. Although a
      reduction in crude risk of some bacterial infections with filgrastim use was
      detected, after adjustment for potentially confounding factors these risks were
      smaller and no longer statistically significant.

PMID- 11964533
TI  - Longitudinal assessment of the effects of drug and alcohol abuse on HIV-1
      treatment outcomes in an urban clinic.
AB  - OBJECTIVE: To assess the temporal association of changes in substance abuse with
      antiretroviral therapy use and adherence, HIV-1 RNA suppression, and CD4 cell
      count changes in patients attending an urban clinic. DESIGN: Prospective cohort
      study. METHODS: Six-hundred and ninety-five HIV-1-infected individuals, who
      completed two or more semi-annual standardized surveys and in whom antiretroviral
      therapy was indicated, were included in the analysis. Surveys addressed
      antiretroviral therapy use and adherence, and use of illicit drugs and alcohol.
      Substance abuse was defined as active heroin, cocaine, or heavy alcohol use in
      the 6 months preceding survey. The units of analysis were consecutive pairs of
      surveys (couplets) in individual participants. Couplets in which participants
      denied substance abuse in both surveys were compared to couplets in which
      participants switched from non-use to substance abuse, and couplets in which
      participants reported substance abuse in both surveys were compared to couplets
      where participants switched from substance abuse to non-use. RESULTS: Switching
      from non-use to substance abuse was strongly associated with worsening
      antiretroviral therapy use and adherence, less frequent HIV-1 RNA suppression,
      and blunted CD4 cell increases, compared to remaining free of substance abuse.
      Alternatively, switching from substance abuse to non-use was strongly associated
      with improvements in antiretroviral therapy use and adherence, and HIV-1
      treatment outcomes, compared to persisting with substance abuse. CONCLUSIONS:
      This longitudinal study highlights the dynamic nature of substance abuse and its
      temporal association with the effectiveness of HIV-1 treatment in patients
      attending an inner-city clinic.

PMID- 11964535
TI  - Invasive cervical cancer as an AIDS-defining illness in Europe.
AB  - OBJECTIVE(S): To evaluate the frequency and correlates of invasive cervical
      cancer (ICC) as an AIDS-defining illness (ADI) in Europe. DESIGN: Statistical
      analysis of data from: national AIDS surveillance systems of 15 European
      countries with >or= 50 female AIDS cases; and from population-based cancer
      registries of the same nations. METHODS: AIDS cases notified between 1993 (when
      ICC was included among ADI) and 1999 in women aged 20-49 years were taken into
      consideration. The association between the presence of ICC as an ADI and
      potential determinants was assessed by calculation of odds ratios (OR) and 95%
      confidence intervals (CI). Country-specific incidence rates of ICC in women aged
      20-49 years were correlated with selected AIDS-associated variables by means of
      the Pearson correlation coefficient (r). RESULTS: The OR of having ICC as an ADI
      increased with age and was significantly elevated in southern (3.1) and central
      (2.5) compared with northern Europe. It was also increased among injecting drug
      users (IDU; 1.5). The proportion of ICC as ADI was inversely correlated with
      incidence rates of ICC in the general female population, but directly correlated
      with the proportion of IDU among female AIDS cases. CONCLUSIONS: The frequency of
      ICC as an ADI in Europe was independent from the background risk of ICC in the
      general population. It was higher where IDU predominated among female AIDS cases
      and where population-based ICC screening programs were less effective.

PMID- 11964534
TI  - Attitudes towards highly active antiretroviral therapy are associated with sexual
      risk taking among HIV-infected and uninfected homosexual men.
AB  - OBJECTIVE: To determine whether attitudes towards highly active antiretroviral
      therapy (HAART) are associated with unprotected anal sex among sexually active
      homosexual men. DESIGN: Cross-sectional study nested within an ongoing
      prospective cohort study. SETTING: Multicenter AIDS Cohort Study, from April
      through September 1999. PARTICIPANTS: Five-hundred and forty-seven homosexual men
      reporting anal sex (218 HIV-negative and 329 HIV-positive) during study
      interviews in 1999, including a 20-item validated scale on attitudes toward HAART
      and HIV risk behaviors (e.g., 'Because of HAART, I am less concerned about
      becoming HIV-infected or infecting someone'), and safer sex fatigue (e.g., 'I am
      tired of always having safer sex'). MAIN OUTCOME MEASURES: Self-reported
      unprotected receptive anal sex (RAS) and insertive anal sex (IAS) in the prior 6
      months. RESULTS: More than 50% of HIV-negative and HIV-positive men who reported
      having anal sex also reported recent unprotected RAS and/or IAS. HIV-negative men
      who most agreed that HAART reduced concern about becoming infected were more
      likely to report unprotected RAS compared to other HIV-negative men [adjusted
      odds ratio (AOR), 3.31; 95% confidence interval (CI), 1.27-8.62]. Moreover, HIV
      positive men with greatest reduced concern due to HAART or safer sex fatigue were
      more likely to report unprotected IAS (AOR, 6.05; 95% CI, 2.24-16.63 and AOR,
      4.57; 95% CI, 1.70-12.24, respectively) compared to other HIV-positive men.
      CONCLUSIONS: Among sexually active homosexual men, lessened concern about HIV
      transmission due to HAART was strongly associated with sexual risk taking, as was
      safer sex fatigue among HIV-positive men. Prevention programs should take into
      account underlying attitudes for unprotected sex in the era of HAART among both
      HIV-infected and uninfected men.

PMID- 11964536
TI  - To stop or not to stop: that is the question, but what is the answer?

PMID- 11964537
TI  - Naturally HIV-1 seroconverters with lowest viral load have best prognosis, but in
      time lose control of viraemia.

PMID- 11964539
TI  - Drug interaction between amprenavir and lopinavir/ritonavir in salvage therapy.

PMID- 11964538
TI  - Genotypic drug resistance during HIV-1 primary infection in France (1996-1999):
      frequency and response to treatment.

PMID- 11964541
TI  - The utility of inhibitory quotients in determining the relative potency of
      protease inhibitors.

PMID- 11964540
TI  - Delavirdine increases drug exposure of ritonavir-boosted protease inhibitors.

PMID- 11964542
TI  - Dietary supplements in the treatment of nucleoside reverse transcriptase
      inhibitor-related mitochondrial toxicity.

PMID- 11964543
TI  - Severe HIV-associated thrombocytopenia despite effective highly active
      antiretroviral therapy in a vertically infected child.

PMID- 11964545
TI  - Eruptive angiolipomas associated with antiretroviral therapy.

PMID- 11964544
TI  - Osteosclerosis and periostal new bone formation during indinavir therapy.

PMID- 11964546
TI  - AIDS-related Kaposi's sarcoma with chylothorax and pericardial involvement
      satisfactorily treated with liposomal doxorubicin.

PMID- 11964547
TI  - Tuberculosis preventative treatment also prevented diarrhoea in HIV-infected
      patients in Zambia.

PMID- 11964548
TI  - Chemokine receptor polymorphisms and GB virus C status in HIV-positive patients.

PMID- 11964550
TI  - Response to Ronald Gray, Male circumcision and HIV acquisition and transmission:
      cohort studies in Rakai, Uganda ( 2000, 14:2371-2381).

PMID- 11964552
TI  - Is timing everything? Doctors research when to start HAART.

PMID- 11964551
TI  - Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a
      randomized, placebo-controlled study.
AB  - BACKGROUND: Therapy with HIV protease inhibitors (PI) causes insulin resistance
      even in the absence of HIV infection, hyperlipidemia or changes in body
      composition. The mechanism of the effects on insulin action is unknown. In vitro
      studies suggest that PI selectively and rapidly inhibit the activity of the
      insulin-responsive glucose transporter GLUT-4. We hypothesized that a single dose
      of the PI indinavir resulting in therapeutic plasma concentrations would acutely
      decrease insulin-stimulated glucose disposal in healthy human volunteers.
      METHODS: Randomized, double-blind, cross-over study comparing the effect of 1200
      mg of orally administered indinavir and placebo on insulin-stimulated glucose
      disposal during a 180-min euglycemic, hyperinsulinemic clamp. Six healthy HIV
      seronegative adult male volunteers were studied twice with 7 to 10 days between
      studies. RESULTS: There were no significant differences in baseline fasting body
      weight, or plasma glucose, insulin, lipid and lipoprotein levels between placebo-
      and indinavir-treated subjects. During steady-state (t60-180 min) insulin reached
      comparable levels (394 +/- 13 versus 390 +/- 11 pmol/l) and glucose was clamped
      at approximately 4.4 mmol/l under both conditions. The average maximum
      concentration of indinavir was 9.4 +/- 2.2 microM and the 2-h area under the
      curve was 13.5 +/- 3.1 microM.h. Insulin-stimulated glucose disposal per unit of
      insulin (M/I) decreased in all subjects from 14.1 +/- 1.2 to 9.2 +/- 0.8
      mg/kg.min per microUI/ml (95% confidence interval for change, 3.7-6.1; P < 0.001)
      on indinavir (average decrease, 34.1 +/- 9.2%). The non-oxidative component of
      total glucose disposal (storage) decreased from 3.9 +/- 1.8 to 1.9 +/- 0.9
      mg/kg.min (P < 0.01). Free fatty acid levels were not significantly different at
      baseline and were suppressed equally with insulin administration during both
      studies. CONCLUSIONS: A single dose of indinavir acutely decreases total and non
      oxidative insulin-stimulated glucose disposal during a euglycemic,
      hyperinsulinemic clamp. Our data are compatible with the hypothesis that an acute
      effect of indinavir on glucose disposal in humans is mediated by a direct
      blockade of GLUT-4 transporters.

PMID- 11964553
TI  - Reciprocal congenics defining individual quantitative trait Loci for
      sedative/hypnotic sensitivity to ethanol.
AB  - BACKGROUND: We have identified four major genes or quantitative trait loci (QTLs)
      that determine duration of loss of righting reflex (LORR), induced by sedative
      doses of ethanol: Lore1, Lore2, Lore4, and Lore5. Together these genes explain
      more than 50% of the phenotypic variance for sensitivity to the sedative/hypnotic
      effects of ethanol between the Inbred Long Sleep (ILS) and Inbred Short Sleep
      (ISS) strains of mice. The derivation of these strains is reviewed here. METHODS:
      Each QTL has been bred onto the opposite background (ILS or ISS) through 10
      rounds of backcrossing by using QTL-marker-assisted counter selection to produce
      reciprocal congenic strains. Mice were genotyped for markers that flanked each of
      the QTLs. Selection for the donor at the desired QTL, and against donor markers
      at the other four QTLs, allowed rapid fixation of the genetic background.
      Phenotypic assessment in the ISS-recipient congenic strains was conducted
      throughout the backcross. RESULTS: By the N5 generation, phenotypic assessments
      failed to detect significant effects in some sublines; these sublines were
      discarded and positive lines split to create new replicate sublines. In the N10,
      all sublines retained the phenotypic difference between heterozygotes and ISS
      homozygotes; however, the expected additive effect was not found in the Lore1
      congenics. On the ILS background, each Lore was captured, as shown by the
      expected differential LORR. Two strains on the ILS background, and one on the
      ISS, exhibited the differential effect on blood ethanol concentration associated
      with the donor strain. CONCLUSIONS: Congenic strains represent an important
      resource for confirmation of previously identified QTLs, for identification and
      mapping of additional phenotypes, and for exclusion of candidate genes. QTL
      marker-assisted selection rapidly stabilized the genetic background within four
      generations (based on phenotypic assessments); however, phenotypic selection
      during the backcrossing to generate congenic strains did not contribute to the
      successful capture of the ISS QTLs.

PMID- 11964554
TI  - In vitro exposure to malondialdehyde-acetaldehyde adducted protein inhibits cell
      proliferation and viability.
AB  - BACKGROUND: Circulating antibodies against malondialdehyde-acetaldehyde (MAA)
      haptenated proteins are increased significantly in patients with alcohol-induced
      cirrhosis and hepatitis and are associated with severity of liver damage.
      Additionally, MAA haptenated proteins are highly immunogenic without the use of
      adjuvant and have been suggested to induce autoreactive responses. The mechanism
      of this immunogenicity is currently unknown but may be mediated by cell death in
      a similar manner as other autoimmune diseases such as systemic lupus
      erythematosus, mixed connective tissue disease, myositis, and Sjogren's disease.
      METHODS: Antigen-presenting cells, lymphocytes, and hepatocytes were exposed to
      different levels of MAA haptenated hen egg lysozyme and assessed by [3H]thymidine
      incorporation and (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)
      conversion for viability. RESULTS: The cells investigated in this study were
      those that potentially may be involved in the development of autoimmune liver
      damage; they include antigen-presenting cells, lymphocytes, and cells of the
      liver itself. Each cell type was found to be sensitive to MAA haptenated protein
      induced cell death at levels between 690 microM (10 microg/ml) and 6.9 mM (100
      microg/ml), which may be found locally after chronic ethanol consumption. Antigen
      presenting cells (macrophage and B cells) were found to be activated at
      concentrations just under those levels associated with cell death. CONCLUSIONS: A
      dose response to MAA haptenated protein-induced cell death is seen in antigen
      presenting cells, lymphocytes, and hepatocytes in vitro. Recent reports have
      associated both apoptotic and necrotic cell death with the development of
      autoimmune disease; thus, it is possible that this may be one mechanism by which
      in vivo immunogenicity is mediated by aldehyde haptenated proteins.

PMID- 11964555
TI  - Effect of gender and estrous cycle on the pharmacokinetics of ethanol in the rat
      brain.
AB  - BACKGROUND: Aspects of ethanol pharmacokinetics in the blood, such as
      elimination, are known to vary by gender in the rat. Ethanol concentrations
      reaching the brain, which are relevant in affecting behavior, have not been
      measured rigorously by gender. This study used quantitative microdialysis to
      measure ethanol pharmacokinetics in the nucleus accumbens after a moderate dose
      of ethanol, comparing males with females and females across the estrous cycle.
      METHODS: We administered 1 g/kg ethanol intravenously or intragastrically to male
      and female rats. We measured ethanol concentrations in the nucleus accumbens by
      use of microdialysis with in vivo probe calibration and compared them with
      concentrations in jugular venous blood. RESULTS: After intravenous delivery,
      apparent ethanol elimination was approximately 15% faster in females than males
      from both brain and blood. After intragastric delivery, blood ethanol
      concentrations peaked faster in females than males by approximately 20 min,
      suggesting faster absorption or diffusion from the stomach. Likewise, accumbal
      ethanol concentrations peaked faster in females than males by approximately 25
      min, indicating faster distribution to the brain. These pharmacokinetic
      parameters did not vary across the estrous cycle, nor were they influenced
      significantly by body water. CONCLUSIONS: This study provides the first
      quantitative measurement of ethanol concentrations and, thus, pharmacokinetics in
      the brain of awake rats. If ethanol distribution to the brain varies between
      genders, as these results suggest, then differences in the pharmacological
      response to ethanol can be expected, providing a rationale for studying the
      pharmacodynamics of ethanol in the brain of the self-administering rat.

PMID- 11964556
TI  - Antagonistic effects of dopaminergic signaling and ethanol on protein kinase A
      mediated phosphorylation of DARPP-32 and the NR1 subunit of the NMDA receptor.
AB  - BACKGROUND: This article extends our initial investigation of the interactions
      between dopamine and glutamate receptor systems after acute exposure to ethanol.
      DARPP-32 (dopamine and cyclic adenosine monophosphate-regulated phosphoprotein of
      approximate molecular weight 32 kDa) is an important regulator of protein
      phosphatase-1 that in turn regulates a large number of effectors, including the
      NMDA receptor. METHODS: We measured the protein kinase A (PKA)-mediated
      phosphorylation of DARPP-32 and the NR1 subunit of the NMDA receptor. Initially,
      corpus striatum was assayed after intraperitoneal treatment of mice with the D1
      agonist SKF82958, the D2 agonist and anticraving drug bromocriptine, or ethanol.
      In other experiments we blocked D1 receptors with the selective D1 antagonist
      SCH23390 or blocked D2 receptors with the selective D2 antagonist eticlopride.
      Finally, we examined combinations of some dopaminergic drugs with and without
      ethanol. RESULTS: SKF82958 alone significantly increased PKA-mediated
      phosphorylation of both DARPP-32 and NR1. Bromocriptine alone had no effect on
      pDARPP-32 or on pNR1. However, when D1 receptors were blocked, bromocriptine
      reduced the PKA-mediated phosphorylation of both DARPP-32 and NR1. Coincident
      treatment with bromocriptine and ethanol reversed both of these effects with D1
      receptors blocked. The combination of eticlopride (D2 blocker) and SF82958 (D1
      agonist) did not significantly alter either pDARPP-32 or pNR1. CONCLUSIONS: These
      data demonstrate antagonistic effects of acute ethanol exposure on D1 signaling
      in vivo and the potential of acute in vivo challenge protocols to help fill gaps
      in the understanding of ethanol's effects on protein phosphorylation.

PMID- 11964557
TI  - Bidirectional modulation of spatial working memory by ethanol.
AB  - BACKGROUND: It is common knowledge that ethanol causes cognitive and memory
      impairments. Although these deficits are attributed to its central depressant
      properties, ethanol has biphasic effects and at low doses can produce excitatory
      actions. METHODS: Here we examined whether ethanol could have biphasic effects on
      performance in a delayed alternation task in a T-maze, a behavioral test of
      working memory. RESULTS: A dose-response study showed that intermediate doses of
      ethanol (1 g/kg) were associated with impairments of working memory in rats, as
      assessed at short intertrial intervals (10 sec). In contrast, at longer delays
      (120 sec), when the delayed alternation performance was reduced markedly in
      controls, a lower dose of ethanol (0.5 g/kg) significantly improved working
      memory. CONCLUSIONS: These results demonstrate a dose-dependent, bidirectional
      effect of ethanol on working memory and implicate the prefrontal cortex, the site
      of working memory function, as a target of ethanol action. The cognitive
      improvements caused by low, excitatory doses of ethanol may be perceived as
      rewarding and could have relevance for chronic ethanol consumption in humans.

PMID- 11964558
TI  - Early-onset alcoholism with conduct disorder: go/no go learning deficits, working
      memory capacity, and personality.
AB  - BACKGROUND: Two studies were conducted to investigate the disinhibitory
      mechanisms that (1) discriminate early-onset alcoholism (EOA) with conduct
      disorder (CD; antisocial EOA) from a non-antisocial subtype of EOA and (2) are
      associated with novelty-seeking and low harm avoidance. METHODS: Young adults
      with antisocial EOA (n = 96), with non-antisocial EOA (without CD; n = 80), with
      CD alone (n = 50), and controls (n = 125) were given two go/no go tasks (one with
      monetary loss and the other with shock punishment), the Digit Span test (working
      memory capacity), and personality measures of harm avoidance, novelty
      seeking/impulsivity, excitement-seeking, and negative affectivity. RESULTS: Study
      1 revealed that antisocial EOA subjects had poor behavioral inhibition compared
      with non-antisocial EOAs and controls on both go/no go tasks and with the CD
      alone group on the monetary-loss task. Low Digit Span scores accentuated poor
      inhibition in antisocial EOAs on the monetary loss, but not the shock task. EOA
      with low Digit Span was associated with higher hit rates on the shock task. Study
      2 revealed that antisocial EOAs had high novelty-seeking/impulsivity and low harm
      avoidance compared with both non-antisocial EOAs and controls. Low harm avoidance
      was associated with poor inhibition with shock punishment, and this association
      was mediated by CD. For subjects with low Digit Span scores, novelty
      seeking/impulsivity was associated with poor inhibition to monetary-loss
      punishment and higher hit rates to shock punishment. CONCLUSIONS: The results
      suggest two disinhibitory mechanisms that distinguish antisocial from non
      antisocial EOA: an increased sensitivity to reward in nonaversive contexts
      associated with novelty-seeking/impulsivity and a decreased sensitivity to
      punishment in aversive contexts associated with low harm avoidance. Results also
      suggest that EOA and novelty-seeking/impulsivity are associated with a greater
      response to rewards in those with low working memory capacity.

PMID- 11964559
TI  - Automating standard alcohol use assessment instruments via interactive voice
      response technology.
AB  - BACKGROUND: Interactive voice response (IVR) technology integrates touch-tone
      telephones with computer-automated data processing. IVR offers a convenient,
      efficient method for remote collection of self-report data. METHODS: Twenty-six
      subjects recruited from an outpatient alcohol treatment center completed IVR and
      paper/pencil versions of a demographic and drinking history questionnaire, Stages
      of Change Readiness and Treatment Eagerness Scale, Drinker Inventory of
      Consequences, Obsessive-Compulsive Drinking Scale, Alcohol Dependence Scale, and
      two numerical rating scales of craving and desire to drink during the prior week.
      Administration of the instruments in both formats was repeated 1 week later. The
      order of administration method was counterbalanced between subjects and reversed
      across data collection sessions. Scale and subscale scores from both methods were
      correlated within sessions. Test-retest correlations were also calculated for
      each method. A criterion of alpha = 0.01 was used to control type I statistical
      error. RESULTS: Intermethod correlations within each session were significant for
      all of the instruments administered. Test-retest correlations for both methods
      were also significant, except for the numerical ratings. Scores on the Alcohol
      Dependence Scale obtained via IVR were significantly lower than those collected
      by paper/pencil. Other differences between the data collection methods or across
      the sessions were inconsistent. The average IVR call length was 34 min and 23
      sec. Paper/pencil forms required an average of 18 min and 38 sec to complete and
      an additional 10 min and 17 sec for data entry. CONCLUSIONS: IVR technology
      provides a convenient alternative to collecting self-report measures of treatment
      outcomes. Both paper/pencil and IVR assessments provide highly convergent data
      and demonstrate good test-retest reliability. Alcohol Dependence Scale score
      differences between methods highlight special considerations for IVR adaptation
      of existing paper/pencil instruments. Benefits of IVR include procedural
      standardization, automatic data scoring, direct electronic storage, and remote
      accessibility from multiple locations.

PMID- 11964560
TI  - Injury among detoxification patients: alcohol users' greater risk.
AB  - BACKGROUND: Little information exists about serious injury in alcohol or drug
      abusers who seek detoxification. This study examined injury prevalence, and the
      impact of alcohol use on injury, among alcohol- and drug-dependent persons.
      METHOD: We enrolled patients at a detoxification unit into a prospective cohort
      study and performed follow-up interviews to determine the prevalence of injury.
      Baseline and follow-up (6, 12, 18, and 24 month) data were examined separately by
      using multivariate logistic regression to determine factors associated with self
      reported episodes of serious injury. The main independent variable was self
      reported first and second substances of choice at admission: alcohol only, drug
      only, or both. RESULTS: Overall, 24% of the 470 subjects reported at least one
      instance of serious injury over the 6-month period before detoxification.
      Similarly, approximately 20% of subjects had serious injury during each 6-month
      follow-up period. Injury in the past 6 months was highest among the 63% of
      subjects who reported alcohol as a drug of choice (28-29% vs. 16% for drug only),
      even after we controlled for potential confounders. Analysis of 2-year follow-up
      data revealed a similar association, after we controlled for baseline injury and
      alcohol consumption. CONCLUSIONS: Injury is a serious problem for a substantial
      proportion of patients who undergo detoxification, particularly those with
      alcohol dependence. This marked risk for serious injury persisted for 24 months
      after detoxification. Patients at detoxification, particularly those with alcohol
      problems, represent a high-risk population for injury that may benefit from
      interventions to reduce these preventable complications.

PMID- 11964561
TI  - Beverage choice among native american and african american urban women.
AB  - BACKGROUND: Little is known about beverage preference, especially among
      understudied urban minority populations. Also, most studies do not differentiate
      between beer and malt liquor or among wine, wine coolers, and fortified wine.
      This article examines whether ethnicity or drinking frequency are associated with
      beverage choice, considering six types of alcoholic beverages: beer, wine,
      spirits, malt liquor, fortified wine, and wine coolers. METHODS: Data were
      analyzed from Native American (n = 70) and African American (n = 129) urban
      pregnant women who reported drinking in the 12 months before an index pregnancy.
      A small comparison group of white women (n = 22) was included. Women were queried
      about their consumption of each of six beverage types during the 12 months before
      pregnancy. RESULTS: The alcoholic beverage most often used, adjusted for other
      beverages consumed, was beer, followed in order by spirits, wine coolers, malt
      liquor, wine, and fortified wine. The Native American women preferred beer, which
      accounted for one third of total intake. In contrast, malt liquor and spirits
      each accounted for approximately a quarter of intake among African Americans.
      Compared with other drinkers, women who drank daily were significantly more
      likely to choose the beer and wine products with a higher alcohol content. In
      general, these bivariate results were borne out by multivariate analyses that
      controlled for age, marital status, and education. CONCLUSIONS: These findings
      suggest that when accuracy is desired, alcohol studies focusing on urban African
      American samples (and, to a lesser degree, Native American respondents) should
      consider not just beer, wine, and spirits consumption, but also stronger beer
      products, such as malt liquor; stronger wine products, such as fortified wine;
      and sweeter products, such as wine coolers.

PMID- 11964562
TI  - Alcohol use disorders identification test: factor structure in an adolescent
      emergency department sample.
AB  - BACKGROUND: This study examined whether the factor structure of a modified
      version of the Alcohol Use Disorders Identification Test (AUDIT) represented the
      three intended conceptual domains of consumption, dependence symptoms, and
      alcohol-related consequences in an adolescent sample. Additionally, the utility
      of factor-specific cut scores in identifying patients with DSM-IV alcohol
      diagnoses was investigated. METHODS: Adolescents treated for an injury in an
      emergency department and who reported alcohol use in the last year (n = 173; 57%
      male, 72% white) constituted the study sample. A modified version of the AUDIT
      and the alcohol section of the Diagnostic Interview Schedule for Children were
      administered. The AUDIT's factor structure was determined by confirmatory factor
      analysis and exploratory principal components analysis. Factor-specific cut
      scores that identified adolescents with a DSM-IV alcohol diagnosis were
      determined by using receiver operating characteristic analysis. RESULTS: A two
      factor model representing consumption and dependence/consequences provided the
      best fit to the data. A cut score of 3 on the consumption factor and a cut score
      of 1 on the dependence/consequences factor demonstrated optimal performance in
      identifying patients with alcohol diagnoses. The consumption factor had better
      overall performance compared with the dependence/consequences factor, and it had
      similar overall performance compared with the AUDIT total score. CONCLUSIONS: The
      AUDIT comprised two correlated factors: consumption and dependence/consequences.
      The better performance of the consumption factor in detecting adolescents with
      DSM-IV alcohol diagnoses suggests the utility of including consumption items in
      brief alcohol screens used with adolescents. Results also indicate the need to
      identify developmentally appropriate alcohol-related problems to enhance
      screening performance among adolescents.

PMID- 11964563
TI  - Response of saccadic eye movements to alcohol in African American and non
      Hispanic white college students.
AB  - BACKGROUND: The primary goal of this study was to evaluate how race and sex
      interact with the effects of a moderate dose of alcohol on different ocular
      control subsystems in African American (AA) and non-Hispanic white American (WA)
      college students. METHODS: Horizontal visually guided (VG) saccades and
      antisaccades (AS) of 80 young adult, healthy, AA and WA college students were
      recorded with an infrared system. Subjects ingested 10 aliquots of ethanol at 3
      min intervals, with the aggregate dose precalculated to yield a peak breath
      alcohol concentration (BrAC) of 80 mg%. Data from the measures performed at
      baseline and the ascending and descending limbs of the BrAC at approximately 65
      mg% were compared across race and sex by multivariate analysis of variance. A no
      alcohol control session, performed in 20 of the subjects, documented test-retest
      reliability of the VG and AS measurements. RESULTS: Both AA and WA groups
      demonstrated slowing of AS and VG saccades after alcohol administration, but
      there was no significant effect of 65 mg% alcohol on VG accuracy or AS errors. AS
      latency recovered toward baseline values, whereas the slowing of VG
      latency/velocity progressed, during alcohol exposure. There were significant
      differences between AA and WA groups in the time course of VG latency after
      alcohol but not in most other dependent measures. No significant effects for sex
      were observed in any of the saccade measures. The faster disappearance of alcohol
      in WA compared with AA was replicated, and some measures demonstrated a
      significant, albeit small, negative correlation between the alcohol disappearance
      rate and impairing effects of alcohol on saccades. CONCLUSIONS: Prolonged
      latencies and unchanged percentage of errors reflect a differential effect of
      alcohol on neural function in specific areas (parietal eye field, superior
      colliculus, and frontal eye areas). Race may interact with the effect of ethanol
      on saccadic eye movements in a college student population.

PMID- 11964564
TI  - Ethanol, acetaldehyde, acetate, and lactate levels after alcohol intake in white
      men and women: effect of 4-methylpyrazole.
AB  - BACKGROUND: 4-Methylpyrazole (4-MP), a selective inhibitor of alcohol
      dehydrogenase (ADH), recently has been approved for clinical use in humans. The
      objective was to evaluate the use of 4-MP in human alcohol research and to study
      the effect of 4-MP on various parameters of alcohol metabolism during alcohol
      intoxication. METHODS: 4-MP (10-15 mg/kg orally) or placebo was given in double
      blind fashion to 22 premenopausal women, 12 of whom were using oral
      contraceptives, and 13 men followed by intake of alcohol (0.5 g/kg orally) or
      placebo. RESULTS: A 30% to 40% decrease in the ethanol elimination rate was
      observed in the different groups during pretreatment with 4-MP. The alcohol
      induced increase in plasma acetate was partially inhibited by 4-MP. A significant
      positive correlation was observed between the effect of 4-MP on the alcohol
      induced lactate and acetate elevations. The acetaldehyde was nondetectable (<1
      micromol/liter) in the peripheral venous blood during alcohol intoxication in
      both women and men. During alcohol intoxication, a decrease in breath
      acetaldehyde was found with 4-MP pretreatment in women but not in men.
      CONCLUSION: The alcohol-induced elevation in blood acetate level is caused, in
      part, by ADH-mediated ethanol oxidation. Although no evidence was found for
      measurable acetaldehyde levels in the peripheral venous blood during alcohol
      intoxication, the effect of 4-MP on breath acetaldehyde in women supports the
      view that ADH-mediated acetaldehyde elevations reflected in the airways, but too
      low to be detected in the peripheral venous blood, may occur in women during
      alcohol intoxication in the present experimental conditions.

PMID- 11964565
TI  - Altered EEG responses to ethanol in adult rats exposed to ethanol during
      adolescence.
AB  - BACKGROUND: Adolescent ethanol (EtOH) exposure is a significant health concern
      due to the potential long-term effects of EtOH on the developing brain. However,
      few studies have assessed how exposure to EtOH during adolescence influences the
      response of adults to EtOH after a long period of withdrawal. This study was
      designed to assess long-term changes in EEG activity after EtOH challenge in
      adult rats exposed to EtOH during adolescence. METHODS: Male Sprague Dawley rats
      (n = 24) were exposed to EtOH vapor for 5 days (12 hr/day) between postnatal days
      35 and 40. After maturing to adulthood, rats were implanted with cortical,
      amygdalar, and hippocampal electrodes. Then EEG activity after EtOH challenge
      (0.0-1.5 g/kg) was assessed. RESULTS: There were no EEG differences between
      groups under baseline or vehicle conditions, but EtOH did have differential
      behavioral and electrophysiological effects when adolescent ethanol-exposed rats
      were compared with controls. After 1.5 g/kg EtOH, ethanol-exposed rats displayed
      decreased behavioral indexes of intoxication. In addition, EtOH significantly
      increased 4 to 6 Hz power in the hippocampus and parietal cortex of the control
      group but had no effect on 4 to 6 Hz power in the ethanol-exposed group in either
      of these brain regions. EtOH produced maximal increases in cortical EEG
      variability in control rats after 1.5 g/kg EtOH but produced maximal increases in
      cortical EEG variability in ethanol-exposed rats after 1.0 g/kg EtOH. As a
      result, ethanol-induced increases in EEG variability after 1.5 g/kg ethanol were
      blunted in the ethanol-exposed group compared with the control group.
      CONCLUSIONS: These data demonstrate persistent and brain-region-specific changes
      in the neurobehavioral effects of acute EtOH challenge in adult rats exposed to
      EtOH during adolescence in the absence of baseline neurophysiological
      differences. Decreased EEG responses to high doses of EtOH combined with
      decreased behavioral measures of intoxication suggest that adolescent ethanol
      exposure produces long-lasting tolerance to the sedative effects of ethanol.

PMID- 11964566
TI  - Chronic ethanol consumption increases plasma leptin levels and alters leptin
      receptors in the hypothalamus and the perigonadal fat of C57BL/6 mice.
AB  - BACKGROUND: Leptin, a protein secreted from adipocytes, and leptin receptors,
      expressed in the hypothalamus and fat tissue, regulate energy balance and
      adiposity. Leptin receptors exist as several forms that are delineated by the
      length of their cytoplasmic domains. Only the longest form is physiologically
      active through stimulation of the signal transducers and activators of
      transcription (STAT) second messenger system. Previous studies demonstrated that
      chronic ethanol consumption increases body adiposity and circulating leptin
      levels. This study examined the effect of chronic alcohol intake on the
      expression of leptin receptors and associated STAT second messengers in the
      hypothalamus and fat tissue. METHODS: Female C57BL/6 mice were given water or 20%
      w/v ethanol and Purina 5001 laboratory chow ad libitum for 2 or 5 weeks. Plasma
      leptin levels were determined by radioimmunoassay and body adiposity was
      evaluated by measuring the amount of perigonadal fat. Expression of leptin
      receptors as well as STAT molecules in whole-cell lysates of the hypothalamus and
      the perigonadal fat were assayed by Western blot analysis. RESULTS: Plasma leptin
      and perigonadal fat were increased after 5 weeks. The overall expression of
      leptin receptors was increased while the expression of the physiologically active
      long form of leptin receptor was decreased in the hypothalamus and the
      perigonadal fat of ethanol-consuming mice. Ethanol consumption also decreased
      hypothalamic expression of STAT3, a protein associated with leptin receptor
      activation in this region of the brain. In contrast, STAT1, a protein associated
      with leptin receptor activation in adipose tissue, was significantly elevated in
      the perigonadal fat of ethanol-consuming mice. CONCLUSIONS: Chronic ethanol
      consumption increases the circulating level of leptin, and this is accompanied by
      altered expression of leptin-sensing molecules in the hypothalamus and peripheral
      adipose tissue. These results suggest that chronic ethanol intake affects
      metabolism by altering the leptin system that regulates energy balance.

PMID- 11964567
TI  - Auditory and visual sustained attention in adolescents prenatally exposed to
      alcohol.
AB  - BACKGROUND: Sustained attention problems and impulsivity are reported in
      association with prenatal alcohol exposure and fetal alcohol syndrome, but
      research in this area is limited and contradictory. METHODS: Auditory and visual
      sustained attention were investigated in 265 low-income, predominantly African
      American, adolescents (mean age, 15.12 years; SD, 0.92). Included were 53
      unexposed controls and 128 exposed to alcohol and other drugs prenatally, with 46
      of these exhibiting dysmorphic features and growth retardation, as well as a
      special-education contrast group (n = 84). Sustained attention was measured with
      "AK" subtests from a commercially available Continuous Performance Task program.
      Outcomes included total correct, total errors, omissions, commissions,
      preservations, hit rate, false alarms, reaction time, and response sensitivity
      (d'). A repeated-measures multivariate analysis of variance procedure was used
      with the exposure group (four groups) as the independent variable and
      presentation mode (visual or auditory) and trial block (four blocks) as within
      subject repeated measures. RESULTS: There was an interaction of group with
      presentation mode for total correct, errors, error type, hit rate, and d'. Most
      groups processed visual information more effectively than auditory information.
      In contrast, dysmorphic adolescents performed as effectively when presented with
      auditory stimuli but were less efficient in processing visual information.
      Significantly higher error rates, particularly omission errors [F(3,261) = 7.16;
      p < 0.000], as well as lower d' [F(3,261) = 5.77; p < 0.001], were noted in this
      group. CONCLUSIONS: These results suggest that there may be specific patterns to
      the effect of prenatal alcohol exposure on cognitive performance that can be
      identified during adolescence. In this study of sustained attention, processing
      in the visual modality was more affected than that in the auditory modality.
      Deficits in visual processing seemed to result from insensitivity to target
      stimuli.

PMID- 11964568
TI  - The Alcohol Use Disorders Identification Test (AUDIT): a review of recent
      research.
AB  - BACKGROUND: Efficient, inexpensive screening for early stage alcohol problems is
      important in health care settings. The Alcohol Use Disorders Identification Test
      (AUDIT) has been studied extensively to establish its value in this regard.
      METHODS: A literature search that used EtOH as a database was conducted to
      identify studies published on the AUDIT through September 2001. Keywords used for
      the search were "Alcohol Use Disorders Identification Test" and "AUDIT." All
      studies reporting psychometric properties of the measure were reviewed with
      particular attention being given to the period 1996 and later. A small number of
      additional references were located by noting their citation in other studies
      reviewed. RESULTS: Although more research is needed on non-English versions to
      establish their psychometric properties, at least in its English edition, the
      AUDIT demonstrates sensitivities and specificities comparable, and typically
      superior, to those of other self-report screening measures. Test-retest
      reliability and internal consistency are also quite favorable. For males, the
      AUDIT-C, a shortened version of the AUDIT, appears approximately equal in
      validity to the full scale. CONCLUSIONS: Recent research continues to support use
      of the AUDIT as a means of screening for alcohol use disorders in health care
      settings in the United States.

PMID- 11964569
TI  - Central nervous system mechanisms in alcohol relapse.
AB  - BACKGROUND: Alcohol relapse is a major problem in the treatment of alcohol abuse
      and alcoholism. Understanding the long-term neuronal alterations that promote
      relapse of alcohol drinking is critical for the development of pharmacotherapies
      to treat alcoholism and alcohol abuse. The major objectives of this workshop were
      to present recent findings, by using rodent models, on behavioral and
      neurobiological factors that may underlie alcohol relapse and the results of
      clinical and pharmacological treatment strategies for preventing relapse.
      METHODS: Prolonged ethanol drinking and repeated periods of alcohol deprivation
      were studied in nonselected rats and in rats selectively bred for high alcohol
      preference (P rat). The expression of a robust alcohol deprivation effect (ADE)
      was used as a model for alcohol relapse in rodents. Operant techniques were used
      to examine responding for ethanol after deprivation in both rats and C57BL/6J
      mice. Environmental cues and stress were used to assess their effects on
      reinstatement of alcohol responding. Microdialysis and [14C]-2-deoxyglucose
      techniques were used to examine neuronal alterations associated with alcohol
      relapse. RESULTS: Prolonged free-choice ethanol drinking followed by deprivation
      produced an ADE in both stock and P rats. These rats demonstrated loss of control
      on reinstatement after chronic drinking and after prolonged deprivation.
      Acamprosate and naltrexone effectively reduced the ADE in stock rats. Stress
      reinstated operant responding for alcohol, and rats trained to associate a cue
      with ethanol presentation increased responding on the ethanol-associated lever in
      the absence of ethanol. After repeated deprivations, P rats shifted their
      preference toward drinking higher concentrations of ethanol, which increased the
      magnitude and duration of the ADE. Stock rats also shifted their preference
      toward solutions with higher ethanol concentrations and demonstrated a loss of
      control after prolonged ethanol drinking and deprivation. Long-lasting
      alterations in neuronal activity, serotonin-3 receptor function, and dopamine
      neurotransmission within the mesolimbic system were evident after chronic
      drinking that followed a prolonged deprivation period. CONCLUSIONS: The ADE is a
      useful model for studying alcohol relapse in both rats and mice. The potential
      validity of this model is supported by the findings that acamprosate and
      naltrexone are effective in preventing the ADE in rodents, and both compounds
      have gained recognition for their therapeutic effects in clinical populations.
      Genetics, stress, and environmental cues are all important factors that influence
      alcohol relapse. Long-term alterations in neuronal activity within the mesolimbic
      system, which possibly involve dopamine and serotonin, may underlie alcohol
      relapse.

PMID- 11964571
TI  - Physical fitness of lower limb amputees.
AB  - OBJECTIVE: To investigate the cardiorespiratory endurance of the physical fitness
      of amputees and able-bodied subjects of the same ages and to demonstrate
      deterioration of the physical fitness of the amputees. DESIGN: The test subjects
      were 31 amputees. Eighteen able-bodied persons served as controls. The
      incremental exercise test was performed to evaluate physical fitness. Sixteen of
      31 amputees underwent endurance training by using a cycle ergometer driven by the
      intact leg, and their physical fitness was evaluated after completion of the
      endurance training program. RESULTS: The Vo2max, anaerobic threshold, and maximum
      workload for the amputees were significantly lower than those of the able-bodied
      group. The equivalent values for the endurance training group before exercise
      treatment were 18.0, 12.1, and 63.9, respectively. After exercise treatment,
      these values significantly increased, and there was no significant difference
      from the able-bodied subjects. CONCLUSIONS: This study showed that the physical
      fitness of amputees was clearly lower than that of the able-bodied subjects and
      that the amputees were able to recover from a poorly conditioned status after
      endurance training.

PMID- 11964570
TI  - Ethanol and membrane protein trafficking: diverse mechanisms of ethanol action.
AB  - This article represents the proceedings of a symposium at the 2001 RSA Meeting in
      Montreal, Quebec. The cochairs were Laura E. Nagy and M. Raj Lakshman. The
      presentations were (1) Ethanol and protein trafficking in liver: modifications of
      small GTP binding proteins (Rabs), by M. Raj Lakshman; (2) Impaired receptor
      mediated endocytosis: its role in alcoholic liver injury, by Carol A. Casey; (3)
      Ethanol and L1 mediated neurite outgrowth: receptor recycling and L1 signal
      transduction, by Cynthia F. Bearer; and (4) Ethanol and glucose transport, GLUT4
      vesicle trafficking, by Laura E. Nagy.

PMID- 11964572
TI  - Activation of paraspinal and abdominal muscles during manually assisted and
      nonassisted therapeutic exercise.
AB  - OBJECTIVE: To assess the activities of the paraspinal and abdominal muscles
      during manually assisted therapeutic exercises (MATEs) and nonassisted
      therapeutic exercises (NATEs) that are used in the initial phases of the
      progressive exercise programs designed for the treatment of low back pain.
      DESIGN: Thirteen healthy subjects volunteered in the study. Surface
      electromyography (EMG) was recorded. The recorded EMG signal was averaged and
      normalized to the maximal EMG amplitude obtained during the maximal voluntary
      contraction (%EMGmax). RESULTS: In general, the %EMGmax values were higher during
      NATEs than during MATEs. Sitting seemed to activate lumbar L5 level paraspinal
      muscles to the same extent as MATEs. CONCLUSION: MATEs require only minimal trunk
      muscle activities, and thus, they may not be sufficiently intense to improve the
      trunk muscle performance. NATEs require high trunk muscle activities that are
      adequate for improving the trunk muscle performance, but they may cause high
      compressive loading of the lumbar spine, and if unchecked, this can aggravate low
      back pain.

PMID- 11964573
TI  - Improvement of cardiorespiratory function after percutaneous transluminal
      coronary angioplasty or coronary artery bypass grafting.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of a 3-mo
      training program for patients with either a percutaneous transluminal coronary
      angioplasty (PTCA) or a coronary artery bypass grafting (CABG). DESIGN: Forty
      four patients participated in a 3-mo outpatient cardiac rehabilitation program.
      Graded exercise tests with gas analysis were conducted before and after training
      to evaluate the changes of cardiorespiratory function. RESULTS: In the
      pretraining examination, the PTCA group showed a higher peak oxygen uptake
      (VO2peak) and work rate than the CABG group. In the posttraining examination, the
      PTCA group increased 14.6% in VO2peak. Meanwhile, the CABG group increased 32.8%
      in VO2peak. At the ventilatory threshold, both groups also significantly
      increased in Vo2. CONCLUSIONS: A 3-mo cardiac rehabilitation program for patients
      with PTCA or CABG could favorably enhance their cardiorespiratory function.
      Although the pretraining VO2peak was lower for the patients with CABG, their
      training potential was greater, and hence they could achieve a similar level of
      aerobic capacity as the PTCA group.

PMID- 11964574
TI  - Effects of a calcium channel blocker on electrical activity in myofascial trigger
      spots of rabbits.
AB  - OBJECTIVE: This study investigated the effect of a calcium channel blocking
      agent, verapamil, on the spontaneous electrical activity (SEA) in a myofascial
      trigger spot of biceps femoris muscles of rabbits. DESIGN: Left and right legs of
      eight adult New Zealand rabbits were randomly assigned into either experimental
      or control groups to assess the effect of verapamil on SEA. Verapamil and normal
      saline were injected into the external iliac artery for experimental and control
      groups, respectively. The experiment was divided into two phases: Phase A
      investigated the immediate effect of verapamil on SEA of one active locus, and
      phase B studied the effect of verapamil on SEA of 25 different active loci. The
      average integrated value of SEA was used to statistically analyze the effect of
      verapamil on myofascial trigger-spot sensitivity. RESULTS: In phase A, conducted
      on one active locus, the regression analysis results showed that the average
      integrated value in the verapamil group linearly decreased with time, but the
      average integrated value did not significantly change with time in the control
      group. In phase B, which analyzed 25 different active loci, the results indicated
      that the mean average integrated values in the verapamil group was significantly
      lower than that of the control group. CONCLUSIONS: Calcium channel blockers can
      effectively inhibit the SEA of myofascial trigger spots.

PMID- 11964575
TI  - Power spectrum analysis of heart rate variability for cerebral palsy patients.
AB  - OBJECTIVE: The prevalence of bowel and bladder dysfunction, hyperhidrosis, and
      poor cardiopulmonary endurance is higher for children with cerebral palsy than
      for the general population. The purpose of this study was to investigate the
      autonomic function for patients with cerebral palsy. DESIGN: Thirty patients with
      cerebral palsy and 30 control subjects were enrolled in this study. Power
      spectrum analysis of heart rate variability was performed under standardized
      conditions. RESULTS: In both the supine and head-up positions for test subjects,
      there was no significant difference for the low frequency component of heart rate
      variability, high frequency component of heart rate variability, or the low
      frequency/high frequency ratio between the study and control groups. A
      significantly greater low frequency component of heart rate variability, smaller
      high frequency component of heart rate variability, and greater low
      frequency/high frequency ratio while in the head-up position compared with the
      supine position was noted for the control group, which implies normal
      sympathovagal balance. A similar phenomenon was not observed for the study group.
      CONCLUSIONS: The disturbed balance of activity between the sympathetic and
      parasympathetic nervous system observed in the study might result from the loss
      of hemispheric influence in patients with cerebral palsy; however, further
      investigation is clearly necessary.

PMID- 11964576
TI  - Botulinum toxin in upper limb spasticity after acquired brain injury: a
      randomized trial comparing dilution techniques.
AB  - OBJECTIVE: To compare the efficacy of two different volume preparations of the
      same dose of botulinum toxin-A in relieving spasticity in wrist and finger
      flexors secondary to acquired brain injury. DESIGN: Thirteen adult patients who
      had modified Ashworth scale scores of 3 for both wrist and finger flexors were
      included in this randomized, controlled trial. Wrist and finger flexors were each
      injected. Blinded modified Ashworth scale ratings of wrist and finger flexor
      spasticity were measured. RESULTS: Spasticity in both muscles decreased
      significantly in both treatment groups. However, the high-volume and low-volume
      groups did not differ significantly in spasticity reduction. CONCLUSIONS: Because
      this preliminary study found no difference in spasticity reduction between high-
      and low-volume preparations of a 60-unit dose of botulinum toxin-A, a larger
      sample study seems warranted to compare the efficacy of high-volume and low
      volume preparations.

PMID- 11964577
TI  - Effects of fluoxetine on the 5-HT1A receptor and recovery of cognitive function
      after traumatic brain injury in rats.
AB  - OBJECTIVE: This study examined the effects of chronic administration of
      fluoxetine, a selective serotonin reuptake inhibitor, on cognitive performance
      and 5-HT1A receptor immunoreactivity following traumatic brain injury. DESIGN:
      Rats received a moderate severity of lateral fluid percussive injury or sham
      injury 24 hr after surgical preparation. Fluoxetine or vehicle was administered
      chronically on postinjury days 1-15. Motor performance and Morris water maze
      performance were assessed on postinjury days 1-5 and 11-15, respectively.
      RESULTS: Results indicated that chronic fluoxetine treatment did not affect motor
      or maze performance. Injured groups showed significantly higher 5-HT1A receptor
      immunoreactivity on postinjury day 15 than sham-injured rats, and fluoxetine
      treatment did not alter 5-HT1A receptor immunoreactivity. CONCLUSIONS: These
      results indicate that chronic postinjury fluoxetine administration did not
      influence the recovery of motor or Morris water maze performance following
      lateral fluid percussive injury. They also indicate that injury-induced changes
      in the 5-HT1A receptor may contribute to traumatic brain injury-induced cognitive
      deficits.

PMID- 11964578
TI  - Health status and functional status in relationship to nursing home subacute
      rehabilitation program outcomes.
AB  - OBJECTIVE: To assess the relationship of health status and functional status to
      key nursing home subacute rehabilitation program outcomes: motor function at
      discharge, discharge destination, and length of stay in the program. DESIGN:
      Using a prospective cohort study design, 164 patients were assessed on entering
      the rehabilitation program for the first time after discharge from an acute
      hospital. Their median length of stay was 40 days. RESULTS: The patients' motor
      function improved over time (P < 0.0001), and a large majority were discharged to
      the community. At admission, health status was positively associated with motor
      function (P < 0.05) and cognitive function (P < 0.01). Higher cognitive function
      and higher motor function at admission were correlated with higher motor function
      at discharge (rs = 0.386, P < 0.0001; rs = 0.563, P < 0.0001 respectively).
      Better health status was independently associated with discharge to the community
      (P < 0.01). Only motor function at admission was independently associated with
      length of stay (P < 0.01). CONCLUSION: Health status and functional status are
      related, and both are independently associated with nursing home subacute
      rehabilitation program outcomes. Therefore, an improvement in one may result in
      an improvement in the other, and both aid in the attainment of positive subacute
      rehabilitation outcomes.

PMID- 11964579
TI  - Medical and rehabilitation issues in classical ballet.
AB  - Classical ballet is a demanding professional occupation, with participants who
      are often underserved in terms of accurate diagnosis and appropriate
      comprehensive medical care. The view that follows is designed to be as global and
      insightful as published to date. Specific rehabilitation considerations, dance
      mechanics, idiosyncratic differential diagnosis, and personality and equipment
      issues are discussed, and a rational view of dogma is presented.

PMID- 11964580
TI  - Classical ballet: the full-contact sport.

PMID- 11964582
TI  - Does the advent of (new) low tidal volumes bring the (old) sigh back to the
      intensive care unit?

PMID- 11964583
TI  - Monitors of depth of anesthesia, quo vadis?

PMID- 11964584
TI  - Sigh improves gas exchange and lung volume in patients with acute respiratory
      distress syndrome undergoing pressure support ventilation.
AB  - BACKGROUND: The aim of our study was to assess the effect of periodic
      hyperinflations (sighs) during pressure support ventilation (PSV) on lung volume,
      gas exchange, and respiratory pattern in patients with early acute respiratory
      distress syndrome (ARDS). METHODS: Thirteen patients undergoing PSV were
      enrolled. The study comprised 3 steps: baseline 1, sigh, and baseline 2, of 1 h
      each. During baseline 1 and baseline 2, patients underwent PSV. Sighs were
      administered once per minute by adding to baseline PSV a 3- to 5-s continuous
      positive airway pressure (CPAP) period, set at a level 20% higher than the peak
      airway pressure of the PSV breaths or at least 35 cm H2O. Mean airway pressure
      was kept constant by reducing the positive end-expiratory pressure (PEEP) during
      the sigh period as required. At the end of each study period, arterial blood gas
      tensions, air flow and pressures traces, end-expiratory lung volume (EELV),
      compliance of respiratory system (Crs), and ventilatory parameters were recorded.
      RESULTS: Pao2 improved (P < 0.001) from baseline 1 (91.4 +/- 27.4 mmHg) to sigh
      (133 +/- 42.5 mmHg), without changes of Paco2. EELV increased (P < 0.01) from
      baseline 1 (1,242 +/- 507 ml) to sigh (1,377 +/- 484 ml). Crs improved (P < 0.01)
      from baseline 1 (40.2 +/- 12.5 ml/cm H2O) to sigh (45.1 +/- 15.3 ml/cm H2O).
      Tidal volume of pressure-supported breaths and the airway occlusion pressure
      (P0.1) decreased (P < 0.01) during the sigh period. There were no significant
      differences between baselines 1 and 2 for all parameters. CONCLUSIONS: The
      addition of 1 sigh per minute during PSV in patients with early ARDS improved gas
      exchange and lung volume and decreased the respiratory drive.

PMID- 11964585
TI  - Effects of recruiting maneuvers in patients with acute respiratory distress
      syndrome ventilated with protective ventilatory strategy.
AB  - BACKGROUND: A lung-protective ventilatory strategy with low tidal volume (VT) has
      been proposed for use in acute respiratory distress syndrome (ARDS). Alveolar
      derecruitment may occur during the use of a lung-protective ventilatory strategy
      and may be prevented by recruiting maneuvers. This study examined the hypothesis
      that the effectiveness of a recruiting maneuver to improve oxygenation in
      patients with ARDS would be influenced by the elastic properties of the lung and
      chest wall. METHODS: Twenty-two patients with ARDS were studied during use of the
      ARDSNet lung-protective ventilatory strategy: VT was set at 6 ml/kg predicted
      body weight and positive end-expiratory pressure (PEEP) and inspiratory oxygen
      fraction (Fio2) were set to obtain an arterial oxygen saturation of 90-95% and/or
      an arterial oxygen partial pressure (Pao2) of 60- 80 mmHg (baseline).
      Measurements of Pao2/Fio2, static volume-pressure curve, recruited volume
      (vertical shift of the volume-pressure curve), and chest wall and lung elastance
      (EstW and EstL: esophageal pressure) were obtained on zero end-expiratory
      pressure, at baseline, and at 2 and 20 min after application of a recruiting
      maneuver (40 cm H2O of continuous positive airway pressure for 40 s). Cardiac
      output (transesophageal Doppler) and mean arterial pressure were measured
      immediately before, during, and immediately after the recruiting maneuver.
      Patients were classified a priori as responders and nonresponders on the basis of
      the occurrence or nonoccurrence of a 50% increase in Pao2/Fio2 after the
      recruiting maneuver. RESULTS: Recruiting maneuvers increased Pao2/Fio2 by 20 +/-
      3% in nonresponders (n = 11) and by 175 +/- 23% (n = 11; mean +/- standard
      deviation) in responders. On zero end-expiratory pressure, EstL (28.4 +/- 2.2 vs.
      24.2 +/- 2.9 cm H2O/l) and EstW (10.4 +/- 1.8 vs. 5.6 +/- 0.8 cm H2O/l) were
      higher in nonresponders than in responders (P < 0.01). Nonresponders had been
      ventilated for a longer period of time than responders (7 +/- 1 vs. 1 +/- 0.3
      days; P < 0.001). Cardiac output and mean arterial pressure decreased by 31 +/- 2
      and 19 +/- 3% in nonresponders and by 2 +/- 1 and 2 +/- 1% in responders (P <
      0.01). CONCLUSIONS: Application of recruiting maneuvers improves oxygenation only
      in patients with early ARDS who do not have impairment of chest wall mechanics
      and with a large potential for recruitment, as indicated by low values of EstL.

PMID- 11964586
TI  - Performance of the ARX-derived auditory evoked potential index as an indicator of
      anesthetic depth: a comparison with bispectral index and hemodynamic measures
      during propofol administration.
AB  - BACKGROUND: Autoregressive modeling with exogenous input of middle-latency
      auditory evoked potential (A-Line autoregressive index [AAI]) has been proposed
      for monitoring anesthetic depth. The aim of the current study was to compare the
      accuracy of this new index with the Bispectral Index (BIS), predicted effect-site
      concentration of propofol, and hemodynamic measures. METHODS: Twenty female
      patients scheduled for ambulatory gynecologic surgery received effect compartment
      controlled infusion of propofol. Target effect-site concentration was started at
      1.5 microg/ml and increased every 4 min by 0.5 microg/ml. At every step, sedation
      level was compared with monitoring values using different clinical scoring
      systems and reaction to noxious stimulus. RESULTS: Bispectral Index, AAI, and
      predicted propofol effect-site concentration were accurate indicators for the
      level of sedation and loss of consciousness. Hemodynamic variables were poor
      indicators of the hypnotic-anesthetic status of the patient. BIS correlated best
      with propofol effect-site concentration, followed by AAI. Hemodynamic
      measurements did not correlate well. No indicators predicted reaction to noxious
      stimulus. Poststimulus, BIS and AAI showed an increase as a result of arousal.
      This reaction occurred more rapidly with the AAI than with BIS. CONCLUSION:
      Bispectral Index, AAI, and predicted propofol effect-site concentration revealed
      information on the level of sedation and loss of consciousness but did not
      predict response to noxious stimulus.

PMID- 11964587
TI  - Automatic CPAP compared with conventional treatment for episodic hypoxemia and
      sleep disturbance after major abdominal surgery.
AB  - BACKGROUND: After major surgery, analgesia with opioids can cause obstructive
      apnea and intermittent hypoxemia, probably from loss of upper airway control.
      Since this resembles the obstructive sleep apnea syndrome, we tested the
      possibility that nasal continuous positive airway pressure (nCPAP) would reduce
      episodes of reduced oxygen saturation and sleep disruption. Because oxygen
      therapy is frequent after surgery, we also assessed the effect of oxygen on sleep
      disruption. METHODS: We recruited 48 patients about to have major abdominal
      surgery. We present data for 34 patients: 27 who received patient-controlled
      intravenous morphine and 7 who received epidural opioid. Treatment was randomized
      to either nCPAP or conventional therapy with an oxygen mask. Alternate periods of
      administration of air and 35% oxygen were used in both groups. If the oxygen
      saturation as measured by pulse oximetry was consistently <90% on air, the
      patient was withdrawn from the study. We measured sleep, arousals, oxygenation,
      episodes of desaturation, and disturbances of respiration. Values are given as
      median and quartiles. RESULTS: The median proportion of time awake was 65% (45
      79%) among control patients and 74% (55-87%) among those undergoing nCPAP. Oxygen
      administration did not affect the sleep pattern. The median frequency of arousals
      per hour of sleep was very similar in each group: during air breathing from
      nCPAP, 125 (76-187), and during air breathing by mask, 116 (84-187). Oxygen
      therapy had no effect. Oxygenation and hypoxemic events were not improved by
      nCPAP. Oxygen therapy improved oxygenation and reduced but did not eliminate
      episodes of desaturation. CONCLUSIONS: Nasal CPAP does not improve sleep and
      oxygenation or reduce hypoxemic events in the first night after major abdominal
      surgery.

PMID- 11964588
TI  - Effects of dexamethasone on intravascular and extravascular fluid balance in
      patients undergoing coronary bypass surgery with cardiopulmonary bypass.
AB  - BACKGROUND: Cardiac surgery with cardiopulmonary bypass is often associated with
      postoperative hemodynamic instability. In this regard beneficial effects of
      corticosteroids are known. The purpose of this study was to investigate whether
      these effects are due mainly to a modification of the intravascular and
      extravascular volume status or whether a more direct improvement of
      cardiovascular performance by corticosteroids is the underlying mechanism.
      METHODS: Twenty patients undergoing elective coronary bypass grafting were
      included in this randomized double-blind study. Patients of the treatment group
      received 1 mg/kg-1 dexamethasone after induction of anesthesia. In addition to
      the use of standard monitors and detailed fluid balance assessments, the
      transpulmonary double-indicator technique was used to measure extravascular lung
      water, total blood volume, and intrathoracic blood volume. Measurements were done
      after induction of anesthesia and 1 h, 6 h, and 20 h after the end of surgery.
      RESULTS: After cardiopulmonary bypass, no relevant increase in extravascular lung
      water was observed, despite highly positive fluid balances in all patients. A
      significantly smaller increase in extravascular fluid content was observed in the
      dexamethasone group. Total blood volume and intrathoracic blood volume did not
      differ in the two groups. Patients pretreated with dexamethasone had a decreased
      requirement for vasoactive substances and, in contrast with the control group, no
      increase in pulmonary artery pressure. CONCLUSIONS: Extravascular fluid but not
      extravascular lung water is increased in patients after surgery with
      cardiopulmonary bypass. Pretreatment of adult patients with 1 mg/kg-1
      dexamethasone before coronary bypass grafting decreases extravascular fluid gain
      and seems to improve postoperative cardiovascular performance. This effect is not
      caused by a better intravascular volume status.

PMID- 11964589
TI  - Usefulness of nitric oxide treatment for pulmonary hypertensive infants during
      cardiac anesthesia.
AB  - BACKGROUND: The beneficial effect of inhaled nitric oxide (NO) on pulmonary
      hypertension is well known. However, the indications for NO inhalation therapy
      for pulmonary hypertension associated with congenital heart lesions are still
      unclear. The aim of the current study was to seek a measure that would predict
      the effectiveness of inhaled NO in infants undergoing cardiac surgery. METHODS:
      Forty-six infants with pulmonary hypertension were studied. Pulmonary vascular
      resistance (PVR) measured at the time of cardiac catheterization was used as an
      indicator and compared with pulmonary arterial pressure/systemic blood pressure
      ratio (Pp/Ps) at the time of weaning from cardiopulmonary bypass. The effect of
      40 ppm of inhaled NO for 15 min was evaluated in patients whose Pp exceeded
      systemic values. RESULTS: Preoperative PVR correlated positively with Pp/Ps at
      the time of weaning from cardiopulmonary bypass (r2 = 0.86; P < 0.05; n = 46). A
      Pp/Ps greater than or equal to 1 was not observed in any cases in which the
      preoperative PVR values were less than 7 Wood units m2; Pp/Ps ratio greater than
      or equal to 1 occurred in four patients. Each of these had PVR values greater
      than 7 Wood units m2. Three of these patients who had PVR values in the 7-12 Wood
      units m2 range were responsive to inhaled NO. The fourth patient, whose PVR value
      was greater than 15 Wood units m2, was unresponsive. Lung biopsy specimens were
      obtained in two patients whose preoperative PVR values were greater than 10 Wood
      units m2. CONCLUSION: Preoperative PVR correlates reasonably well with postbypass
      Pp/Ps.

PMID- 11964591
TI  - Performance of infusion pumps during hyperbaric conditions.
AB  - BACKGROUND: Many hyperbaric facilities use infusion pumps inside the chamber. It
      is therefore important to ensure that this equipment will perform accurately
      during hyperbaric conditions. The authors tested the function and accuracy of the
      Imed 965 and Infutec 520 volumetric infusion pumps, the Easy-pump MZ-257
      peristaltic infusion pump, and the Graseby 3100 syringe pump. METHODS: The
      authors calculated the deviations of infused volumes at low and high rates (12-18
      and 60-100 ml/h) on three different hyperbaric protocols (up to 2.5, 2.8, and 6
      atmospheres absolute [ATA]), resembling a standard hyperbaric oxygen treatment
      and US Navy treatment tables used for decompression illness and for arterial gas
      embolism. Two examples of each pump model were examined in every experiment.
      RESULTS: The Easy-pump MZ-257 failed to function completely beyond a chamber
      pressure of 1.4 ATA, making it unsuitable for use inside the hyperbaric chamber.
      The Graseby 3100 failed to respond to all keyboard functions at 2.5-2.8 ATA,
      making it unsuitable for use in most hyperbaric treatments. The Imed 965
      performed within an acceptable volume deviation (< or =10%) during most
      hyperbaric conditions. During the compression phase of the profiles used, and for
      the low infusion rates only, exceptional volume deviations of 20-40% were
      monitored. The Infutec 520 demonstrated an acceptable deviation (within 10%)
      throughout all the hyperbaric profiles used, unaffected by changes in ambient
      pressure or infusion rate. CONCLUSIONS: Commercially available infusion pumps
      operating during hyperbaric conditions demonstrate substantial variations in
      performance and accuracy. It is therefore important that the hyperbaric facility
      staff make a careful examination of such instruments to anticipate possible
      deviations in the accuracy of the equipment during use.

PMID- 11964590
TI  - Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a
      randomized double-blind, active placebo-controlled, crossover trial.
AB  - BACKGROUND: Phantom and stump pains, common sequelae of limb amputations, are
      significant impediments to rehabilitation of amputees. The pathophysiology and
      optimal treatment of postamputation pain states are unclear. While stump pain may
      result from neuromas in the stump, phantom pain is thought to be related to
      cortical reorganization. The authors hypothesized that morphine and lidocaine may
      have differential effectiveness on stump and phantom pains. METHODS: The authors
      conducted a randomized double-blind, active-placebo-controlled, crossover trial
      to compare the analgesic effects of intravenous morphine and lidocaine on
      postamputation stump and phantom pains. An intravenous bolus followed by an
      intravenous infusion of morphine (0.05 mg/kg bolus + 0.2 mg/kg infusion over 40
      min), lidocaine (1 mg/kg bolus + 4 mg/kg infusion) and the active placebo,
      diphenhydramine (10 mg bolus + 40 mg infusion), were performed on three
      consecutive days. Phantom and stump pain ratings and sedation scores were
      recorded at 5-min intervals using a 0-100 visual analog scale. Pain measures were
      initiated 30 min before drug infusion and continued until 30 min after the end of
      infusion. Subjects' self-reported pain relief and satisfaction were assessed at
      the end of each infusion. RESULTS: Thirty-one of 32 subjects enrolled completed
      the study. Eleven subjects had both stump and phantom pains, 11 and 9 subjects
      had stump and phantom pain alone, respectively. Baseline pain scores were similar
      in the three drug groups. Compared with placebo, morphine reduced both stump and
      phantom pains significantly (P < 0.01). In contrast, lidocaine decreased stump (P
      < 0.01), but not phantom pain. The changes in sedation scores for morphine and
      lidocaine were not significantly different from placebo. Compared with placebo,
      self-reported stump pain relief was significantly greater for lidocaine (P <
      0.05) and morphine (P < 0.01), while phantom pain relief was greater only for
      morphine (P < 0.01). Satisfaction scores were significantly higher for lidocaine
      (mean +/- SD: 39.3 +/- 37.8, P < 0.01) and morphine (45.9 +/- 35.5, P < 0.01)
      when compared with placebo (9.6 +/- 21.0). CONCLUSIONS: Stump pain was diminished
      both by morphine and lidocaine, while phantom pain was diminished only by
      morphine, suggesting that the mechanisms and pharmacological sensitivity of stump
      and phantom pains are different.

PMID- 11964592
TI  - Perioperative visual changes.
AB  - BACKGROUND: The goal of this project was to describe the frequency and natural
      history of perioperative changes in vision. METHODS: The authors performed a
      prospective evaluation of changes in visual accommodation and acuity in adult
      patients undergoing various surgical procedures. Patients were evaluated
      preoperatively and at 1 and 3 days postoperatively. For patients who had
      persistent blurring of vision on the third postoperative day, surveillance was
      extended to 1.5 yr to determine how long the visual changes persisted and if the
      patients required eye-care provider attention for the condition. RESULTS: Twenty
      eight of 671 patients (4.2%) reported new onset of blurred vision lasting at
      least 3 days after surgery. Seven of these 28 patients (1% of total) required
      either new corrective lens or changes in eyeglass or contact prescriptions
      because of persistent blurry vision. Most of the remaining patients reported
      resolution of blurry vision within 1 to 2 months. No significant risk factors for
      this problem were identified. CONCLUSIONS: In this surgical population, changes
      in visual acuity manifest primarily by blurred vision were reported at a
      surprisingly high frequency. For many of these patients, the blurring resolved
      within 2 months without complication, but 25% of patients who had blurred vision
      for 3 days or longer required visits to eye-care providers and either new
      corrective lens or changes in existing prescriptions.

PMID- 11964593
TI  - Standard versus fiberoptic pulmonary artery catheterization for cardiac surgery
      in the Department of Veterans Affairs: a prospective, observational, multicenter
      analysis.
AB  - BACKGROUND: Controversy exists regarding the utility of continuous monitoring of
      mixed venous oxygen saturation (STvo2) during cardiac surgery. During a
      multicenter, prospective, observational study in the Department of Veterans
      Affairs (Cooperative Study #5), frequency of use of standard pulmonary artery
      catheterization (PAC) and STvo2-PAC was recorded. Here the authors relate these
      data to clinical outcomes. METHODS: Logistic and Cox regression models evaluating
      the association of PAC type with mortality, one or more postoperative
      complications, cardiac complications, time to extubation, and intensive care unit
      length of stay were constructed. The number of thermodilution cardiac outputs and
      arterial blood gas analyses performed in the first 24 h postoperatively were
      compared. RESULTS: Data from 3,265 patients undergoing myocardial
      revascularization (81.7%) or valve replacement-repair (18.3%) were considered.
      STvo2-PAC was used in 49% and PAC in 51% of patients. In the 14 hospitals, STvo2
      PAC was used in all patients in four, in some patients in four, and never in six.
      No association of STvo2-PAC use with outcome were observed aside from unexplained
      hospital level effects. A small but statistically significant reduction in the
      number of arterial blood gas analyses (8 +/- 3 vs. 10 +/- 4, P < 0.0001, STvo2
      PAC vs. PAC, respectively) and thermodilution cardiac outputs (14 +/- 8 vs. 15 +/
      9, P < 0.0001, STvo2-PAC vs. PAC, respectively) was observed with use of STvo2
      PAC. CONCLUSIONS: Despite higher cost, STvo2-PAC was commonly used in this
      cohort. Our analysis failed to detect associations with improved outcomes aside
      from a small reduction in resource utilization. The precise role of STvo2-PAC
      remains uncertain.

PMID- 11964594
TI  - Oxygen reverses deficits of cognitive function and memory and increased heart
      rate induced by acute severe isovolemic anemia.
AB  - BACKGROUND: Erythrocytes are transfused to improve oxygen delivery and prevent or
      treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows
      human data processing and degrades memory, increases heart rate, and decreases
      self-assessed energy level. Erythrocyte transfusion is efficacious in reversing
      these effects of acute anemia. We tested the hypothesis that increasing arterial
      oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to
      be equivalent to augmenting hemoglobin concentration by 2-3 g/dl and thus reverse
      the effects of acute anemia. METHODS: Thirty-one healthy volunteers, aged 28 +/-
      4 yr (mean +/- SD), were tested with verbal memory and standard, computerized
      neuropsychologic tests before and twice after acute isovolemic reduction of their
      hemoglobin concentration to 5.7 +/- 0.3 g/dl. Two sets of tests were performed in
      randomized order at the lower hemoglobin concentration: with the volunteer
      breathing room air or oxygen. The subject and those administering the tests and
      recording the results were unaware which gas was administered. As an additional
      control for duration of the experiment, 10 of these volunteers also completed the
      same tests on a separate day, without alteration of hemoglobin concentration, at
      times of the day similar to those on the experimental day. Heart rate, mean
      arterial blood pressure, and self-assessed sense of energy were recorded at the
      time of each test. RESULTS: Reaction time for digit-symbol substitution test
      increased, delayed memory was degraded, mean arterial pressure and energy level
      decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl
      (all P < 0.05). Increasing Pao2 to 406 +/- 47 mmHg reversed the digit-symbol
      substitution test result and the delayed memory changes to values not different
      from those at the baseline hemoglobin concentration of 12.7 +/- 1.0 g/dl, and
      decreased heart rate (P < 0.05). However, mean arterial pressure and energy level
      changes were not altered with increased Pao2 during acute anemia. CONCLUSION: The
      authors confirmed that acute isovolemic anemia subtly slows human reaction time,
      degrades memory, increases heart rate, and decreases energy level. The findings
      of this study support the hypothesis that increasing Pao2 to 350 mmHg or greater
      by breathing oxygen reverses all of these effects of acute anemia except for
      decreased energy.

PMID- 11964595
TI  - Sleep tendency as a measure of recovery after drugs used for ambulatory surgery.
AB  - BACKGROUND: Although tests of psychomotor function indicate that drug effects
      after ambulatory anesthesia are short-lived, patients often feel washed out for
      long periods of time. Among the psychomotor tests that measure different motor
      and cognitive functions, none directly measures sleepiness or alertness. The
      authors hypothesized that sleepiness, measured by a sleep latency test, would be
      a more sensitive indicator of drug effect after an anesthetic than psychomotor
      tests. The second objective was to determine a sedation regimen that produced the
      least residual effect. METHODS: On four separate occasions, volunteers (N = 12)
      received an injection of propofol 2.5 mg/kg; propofol 2.0 mg/kg and fentanyl 2
      microg/kg; propofol 2.0 mg/kg and midazolam 2 mg/70 kg; or midazolam 0.07 mg/kg
      and fentanyl 2 microg/kg. Dependent measures included the multiple sleep latency
      test (MSLT), Maddox Wing and digit symbol substitution tests, auditory and visual
      reaction times, and a divided attention task. RESULTS: The multiple sleep latency
      test demonstrated sleepiness up to 4 h after injection, and in some patients,
      sleepiness continued up to 8 h afterward. Psychomotor function was impaired only
      at 2 h after injection of the drug combination. CONCLUSION: The multiple sleep
      latency test may be a more sensitive measure of a drug's effect than other tests
      of psychomotor function. For up to 8 h after an injection of midazolam and
      fentanyl, patients must consider driving or operating heavy machinery unsafe
      activities.

PMID- 11964596
TI  - Selective synaptic actions of thiopental and its enantiomers.
AB  - BACKGROUND: There is conflicting evidence concerning the extent to which the
      intravenous general anesthetic thiopental acts by enhancing inhibitory gamma
      aminobutyric acid-mediated (GABAergic) synaptic transmission or by inhibiting
      excitatory glutamatergic transmission. Yet there are remarkably few studies on
      the effects of thiopental on functional synapses. In addition, the degree of
      stereoselectivity of thiopental acting at synapses has yet to be tested. METHODS:
      The actions of thiopental and its enantiomers on GABAergic and glutamatergic
      synapses were investigated using voltage clamp techniques on microisland cultures
      of rat hippocampal neurons, a preparation that avoids the confounding effects of
      complex neuronal networks. RESULTS: Racemic thiopental markedly enhanced the
      charge transfer at GABAergic synapses without significantly affecting the peak of
      the postsynaptic current. At a surgically relevant concentration (25 microm),
      charge transfer was increased by approximately 230%. However, even at twice this
      concentration there were no significant effects on glutamatergic postsynaptic
      currents. At GABAergic synapses, thiopental acted stereoselectively, with the S(
      ) enantiomer being approximately twice as effective as the R(+) enantiomer at
      enhancing charge transfer. CONCLUSIONS: Thiopental stereoselectively enhances
      inhibitory GABAergic synaptic transmission in a way that reflects animal
      potencies, supporting the idea that this is a principal mode of action for this
      drug. The absence of any effect on glutamatergic synapses at surgically relevant
      concentrations suggests that the inhibition of these excitatory synapses is not
      an important factor in producing thiopental general anesthesia.

PMID- 11964597
TI  - Mechanisms underlying greater sensitivity of neonatal cardiac muscle to volatile
      anesthetics.
AB  - BACKGROUND: In neonatal heart, plasma membrane Na+-Ca2+ exchange (NCX) and Ca2+
      influx channels play greater roles in intracellular Ca2+ concentration [Ca2+]i
      regulation compared with the sarcoplasmic reticulum (SR). In neonatal (aged 0-3
      days) and adult (aged 84 days) rat cardiac myocytes, we determined the mechanisms
      underlying greater sensitivity of the neonatal myocardium to inhibition by
      volatile anesthetics. METHODS: The effects of 1 and 2 minimum alveolar
      concentration halothane and sevoflurane on Ca2+ influx during electrical
      stimulation in the presence or blockade of NCX and the Ca2+ channel agonist
      BayK8644 were examined. [Ca2+]i responses to caffeine were used to examine
      anesthetic effects on SR Ca2+ release (via ryanodine receptor channels) and
      reuptake (via SR Ca2+ adenosine triphosphatase). Ca2+ influx via NCX was examined
      during rapid activation in the presence of the reversible SR Ca2+ adenosine
      triphosphatase inhibitor cyclopiazonic acid and ryanodine to inhibit the SR.
      Efflux mode NCX was examined during activation by extracellular Na+ in the
      absence of SR reuptake. RESULTS: Intracellular Ca2+ concentration transients
      during electrical stimulation were inhibited to a greater extent in neonates by
      halothane (80%) and sevoflurane (50%). Potentiation of [Ca2+]i responses by
      BayK8644 (160 and 120% control in neonates and adults, respectively) was also
      blunted by anesthetics to a greater extent in neonates. [Ca2+]i responses to
      caffeine in neonates ( approximately 30% adult responses) were inhibited to a
      lesser extent compared with adults (35 vs. 60% by halothane). Both anesthetics
      inhibited Ca2+ reuptake at 2 minimum alveolar concentration, again to a greater
      extent in adults. Reduction in NCX-mediated influx was more pronounced in
      neonates (90%) compared with adults (65%) but was comparable between anesthetics.
      Both anesthetics also reduced NCX-mediated efflux to a greater extent in
      neonates. Potentiation of NCX-mediated Ca2+ efflux by extracellular Na+ and NCX
      mediated Ca2+ influx by intracellular Na+ were both prevented by halothane,
      especially in neonates. CONCLUSIONS: These data indicate that greater myocardial
      depression in neonates induced by volatile anesthetics may be mediated by
      inhibition of NCX and Ca2+ influx channels rather than inhibition of SR Ca2+
      release.

PMID- 11964598
TI  - Preconditioning with hyperbaric oxygen and hyperoxia induces tolerance against
      spinal cord ischemia in rabbits.
AB  - BACKGROUND: The aim of this study was to determine if the ischemic tolerance
      could be induced in the spinal cord by pretreatment with hyperbaric oxygen (HBO)
      and what components of HBO (hyperoxia, hyperbaricity, and combination of these
      two) were critical in the induction of tolerance against ischemic injury.
      METHODS: In experiment 1, 21 rabbits were randomly assigned to one of three
      groups (n = 7 each): animals in the control group received no HBO before spinal
      cord ischemia; animals in the HBO-1 and HBO-2 groups received HBO (2.5 atmosphere
      absolute [ATA], 100% O2) pretreatment 1 h/day for 3 and 5 days before ischemia,
      respectively. In experiment 2, 48 rabbits were randomly assigned to one of four
      groups (n = 12 each): the control group received no HBO (21% O2, 1 ATA, 1 h/day,
      5 days) before spinal cord ischemia; the HB group received 1-h treatment in 21%
      O2 at 2.5 ATA each day for 5 days; the HO group received 1-h treatment in 100%
      oxygen at 1 ATA each day for 5 days; and the HBO group received HBO (2.5 ATA,
      100% O2) treatment 1 h/day for 5 days. Twenty-four hours after the last
      treatment, spinal cord ischemia was induced by an infrarenal aorta clamping for
      20 min. Forty-eight hours after reperfusion, hind-limb motor function and
      histopathology of the spinal cord were examined in a blinded fashion. RESULTS: In
      experiment 1, the neurologic outcome in the HBO-2 group was better than that of
      the control group (P = 0.004). The number of normal neurons in the anterior
      spinal cord in the HBO-2 group was more than that of the control group (P =
      0.021). In experiment 2, the neurologic and histopathologic outcomes in the HBO
      group were better than that of the control group (P < 0.01). The histopathologic
      outcome in the HO group was better than that in the control group (P < 0.05).
      CONCLUSIONS: Serial exposure to high oxygen tension induced ischemic tolerance in
      spinal cord of rabbits. Simple hyperbaricity (2.5 ATA, 21% O2) did not induce
      ischemic tolerance.

PMID- 11964599
TI  - Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with
      the efflux drug transporter P-glycoprotein.
AB  - BACKGROUND: The efflux transporter P-glycoprotein, a member of the adenosine
      triphosphate-binding cassette superfamily, is a major determinant of the
      pharmacokinetics and pharmacodynamics of the opioid loperamide, a well-recognized
      antidiarrheal agent. Animal studies indicate that P-glycoprotein limits morphine
      entry into the brain. In this study, the authors examined whether other opioids
      of importance to anesthesiologists such as fentanyl, sufentanil, and alfentanil,
      and also morphine-6-glucuronide and morphine-3-glucuronide, are P-glycoprotein
      substrates and whether, in turn, these opioids act also as P-glycoprotein
      inhibitors. METHODS: The transcellular movement of the various opioids, including
      loperamide and morphine, was assessed in L-MDR1 (expressing P-glycoprotein) and
      LLC-PK1 cell monolayers (P-glycoprotein expression absent). A preferential basal
      to-apical versus apical-to-basal transport in the L-MDR cells but not the LLC-PK1
      cells is seen for P-glycoprotein substrates. In addition, the effect of the
      various opioids on the transcellular movement of the prototypical P-glycoprotein
      substrate digoxin was examined in Caco-2 cell monolayers. IC50 values were
      calculated according to the Hill equation. RESULTS: Loperamide was a substrate
      showing high dependence on P-glycoprotein in that basal-apical transport was
      nearly 10-fold greater than in the apical-basal direction in L-MDRI cells.
      Morphine also showed a basal-to-apical gradient in the L-MDR1 cell monolayer,
      indicating that it too is a P-glycoprotein substrate, but with less dependence
      than loperamide in that only 1.5-fold greater basal-apical directional transport
      was observed. Fentanyl, sufentanil, and alfentanil did not behave as P
      glycoprotein substrates, whereas the morphine glucuronides did not cross the cell
      monolayers at all, whether P-glycoprotein was present or not. Loperamide,
      sufentanil, fentanyl, and alfentanil inhibited P-glycoprotein-mediated digoxin
      transport in Caco-2 cells with IC50 values of 2.5, 4.5, 6.5, and 112 microm,
      respectively. Morphine and its glucuronides (20 microm) did not inhibit digoxin
      (5 microm) transport in Caco-2 cells, and therefore IC50 values were not
      determined. CONCLUSIONS: Opioids have a wide spectrum of P-glycoprotein activity,
      acting as both substrates and inhibitors, which might contribute to their varying
      central nervous system-related effects.

PMID- 11964600
TI  - Peripheral antinociceptive action of morphine and the synergistic interaction
      with lamotrigine.
AB  - BACKGROUND: Lamotrigine inhibits glutamate release through the preferential
      blockade of voltage-dependent Na+ channels. In contrast, morphine reduces release
      of excitatory amino acids through the activation of opioid receptors and also
      inhibits tetrodotoxin-resistant Na+ channels on peripheral afferent neurons. The
      current study was designed to investigate the antinociceptive effects of locally
      administered morphine and lamotrigine. The interaction between morphine and
      lamotrigine at the periphery was also examined. METHODS: Morphine, lamotrigine,
      or a combination of morphine and lamotrigine was administered locally to female
      Wistar rats, and the antinociceptive effect was determined in the formalin test.
      Isobolographic analyses were used to define the nature of the functional
      interactions between morphine and lamotrigine. RESULTS: Peripheral administration
      of either morphine or lamotrigine produced a dose-related antinociceptive effect.
      Isobolographic analyses revealed that peripheral morphine and lamotrigine
      interacted synergistically in the formalin test. CONCLUSIONS: The study shows a
      functional interaction between lamotrigine and morphine at the peripheral level.

PMID- 11964601
TI  - Radical scavengers protect murine lungs from endotoxin-induced hyporesponsiveness
      to inhaled nitric oxide.
AB  - BACKGROUND: Sepsis is associated with an impaired pulmonary vasodilator response
      to inhaled nitric oxide (NO). A combination of NO and other inflammatory
      mediators appears to be responsible for endotoxin-induced pulmonary vascular
      hyporesponsiveness to inhaled NO. The authors investigated whether scavengers of
      reactive oxygen species could preserve inhaled NO responsiveness in endotoxin
      challenged mice. METHODS: The vasorelaxation to inhaled NO was studied in
      isolated, perfused, and ventilated lungs obtained from mice 16 h after an
      intraperitoneal challenge with saline or 50 mg/kg Escherichia coli
      lipopolysaccharide. In some mice, challenge with saline or lipopolysaccharide was
      followed by intraperitoneal administration of N-acetylcysteine, dimethylthiourea,
      EUK-8, or polyethylene glycol-conjugated catalase. RESULTS: The pulmonary
      vasodilator response of U46619-preconstricted isolated lungs to ventilation with
      0.4, 4, and 40 ppm inhaled NO in lipopolysaccharide-challenged mice was reduced
      to 32, 43, and 60%, respectively, of that observed in saline-challenged mice (P <
      0.0001). Responsiveness to inhaled NO was partially preserved in
      lipopolysaccharide-challenged mice treated with a single dose of N-acetylcysteine
      (150 or 500 mg/kg) or 20 U/g polyethylene glycol-conjugated catalase (all P <
      0.05 vs. lipopolysaccharide alone). Responsiveness to inhaled NO was fully
      preserved by treatment with either dimethylthiourea, EUK-8, two doses of N
      acetylcysteine (150 mg/kg administered 3.5 h apart), or 100 U/g polyethylene
      glycol-conjugated catalase (all P < 0.01 vs. lipopolysaccharide alone).
      CONCLUSIONS: When administered to mice concurrently with lipopolysaccharide
      challenge, reactive oxygen species scavengers prevent impairment of pulmonary
      vasodilation to inhaled NO. Therapy with scavengers of reactive oxygen species
      may provide a means to preserve pulmonary vasodilation to inhaled NO in sepsis
      associated acute lung injury.

PMID- 11964602
TI  - Isoflurane preconditions myocardium against infarction via release of free
      radicals.
AB  - BACKGROUND: Isoflurane exerts cardioprotective effects that mimic the ischemic
      preconditioning phenomenon. Generation of free radicals is implicated in ischemic
      preconditioning. The authors investigated whether isoflurane-induced
      preconditioning may involve release of free radicals. METHODS: Sixty-one alpha
      chloralose-anesthetized rabbits were instrumented for measurement of left
      ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe),
      and myocardial infarct size (triphenyltetrazolium staining). All rabbits were
      subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent
      reperfusion. Rabbits of all six groups underwent a treatment period consisting of
      either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane
      inhalation (1 minimum alveolar concentration end-tidal concentration) followed by
      a 10-min washout period (isoflurane group, n = 12). Four additional groups
      received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg. kg
      1.min-1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100
      microg.kg-1.min-1) during the treatment period with (isoflurane + MPG; n = 11;
      isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11;
      MnTBAP, n = 7). RESULTS: Hemodynamic baseline values were not significantly
      different between groups (LV pressure, 97 +/- 17 mmHg [mean +/- SD]; cardiac
      output, 228 +/- 61 ml/min). During coronary artery occlusion, LV pressure was
      reduced to 91 +/- 17% of baseline and cardiac output to 94 +/- 21%. After 2 h of
      reperfusion, recovery of LV pressure and cardiac output was not significantly
      different between groups (LV pressure, 83 +/- 20%; cardiac output, 86 +/- 23% of
      baseline). Infarct size was reduced from 49 +/- 17% of the area at risk in
      controls to 29 +/- 19% in the isoflurane group (P = 0.04). MPG and MnTBAP
      themselves had no effect on infarct size (MPG, 50 +/- 14%; MnTBAP, 56 +/- 15%),
      but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50
      +/- 24%, P = 0.02; isoflurane + MnTBAP, 55 +/- 10%, P = 0.001). CONCLUSION:
      Isoflurane-induced preconditioning depends on the release of free radicals.

PMID- 11964603
TI  - Preparation of the Siemens KION anesthetic machine for patients susceptible to
      malignant hyperthermia.
AB  - BACKGROUND: Preparation of anesthetic machines for use with malignant
      hyperthermia-susceptible (MHS) patients requires that the machines be flushed
      with clean fresh gas. We investigated the washout of inhalational anesthetics
      from the KION anesthetic machine. METHODS: In part 1, halothane was circulated
      through KION anesthetic machines for either 2 or 12 h using a test lung. The
      times to washout halothane (to 10 parts per million [ppm]) first, from the
      internal circuitry and second, from the ventilator-patient cassette (without the
      carbon dioxide absorber) were determined at 5 and 10 l/min fresh gas flow (FGF).
      In part 2, the rates of washout of halothane or isoflurane from either the KION
      or Ohmeda Excel 210 machines were compared. The effluent gases were analyzed
      using calibrated Datex Capnomac Ultima (Helsinki, Finland) and a Miran LB2
      Portable Ambient Air Analyzer (Foxboro, Norwalk, CT). RESULTS: Halothane was
      washed out of the internal circuitry of the KION within 5 min at 10 l/min FGF.
      Halothane was eliminated from the ventilator-patient cassette in 22 min at the
      same FGF. The times to reach 10 ppm concentration of halothane and isoflurane in
      the KION at 10 l/min FGF, 23 to 25 min, was four-fold greater than those in the
      Ohmeda Excel 210, 6 min. CONCLUSIONS: To prepare the KION anesthetic machine for
      MHS patients, the machine without the carbon dioxide absorber must be flushed
      with 10 l/min FGF for at least 25 min to achieve 10 ppm anesthetic concentration.
      This FGF should be maintained throughout the anesthetic to avoid increases in
      anesthetic concentration in the FGF.

PMID- 11964604
TI  - Isoproterenol inhibits transcription of cardiac cytokine genes induced by
      reactive oxygen intermediates.
AB  - BACKGROUND: Cytokines such as tumor necrosis factor alpha (TNF-alpha) are
      produced by the myocardium in heart disease and might be stimulated by reactive
      oxygen. In some cell types, cyclic adenosine monophosphate (AMP) inhibits TNF
      alpha production. The authors tested the hypothesis that stimulation of cardiac
      beta-adrenergic receptors would inhibit cytokine gene transcription induced by
      reactive oxygen. METHODS: Rat hearts were perfused with buffer containing
      hypoxanthine. Reactive oxygen intermediates were generated by infusion of
      xanthine oxidase. Myocardial mRNA encoding 11 cytokines was determined. TNF
      alpha, interleukin-6, and cyclic AMP were measured in the coronary effluent.
      RESULTS: In control hearts, of the screened RNA, only mRNA encoding interleukin
      1beta, -4, and -6 was detected. Stimulation with hypoxanthine-xanthine oxidase
      (HX-XO) induced detectable mRNA for TNF-alpha and interleukin-5 and increased
      mRNA band density for interleukin-1beta, -4, and -6. Simultaneous infusion of
      isoproterenol inhibited HX-XO-stimulated cytokine gene expression and caused
      release of cyclic AMP into the coronary effluent. In control hearts, TNF-alpha
      was not detected in the coronary effluent. After HX-XO administration, TNF-alpha
      was reliably detected at 60 min and interleukin-6 at 90 min. Simultaneous
      infusion of isoproterenol inhibited TNF-alpha and interleukin-6 release.
      Inclusion of propranolol in the perfusion buffer blocked the isoproterenol
      induced inhibition of HX-XO-stimulated TNF-alpha release and release of cyclic
      AMP into the coronary effluent. In addition, elevating myocardial cyclic AMP with
      forskolin also blocked release of TNF-alpha stimulated by HX-XO. Finally,
      delaying infusion of isoproterenol until 30 min after HX-XO administration still
      suppressed release of TNF-alpha. CONCLUSIONS: Reactive oxygen species activate
      cytokine gene transcription in the myocardium. The sympathetic nervous system,
      acting through beta-receptors to elevate myocardial cyclic AMP, regulates cardiac
      cytokine production by inhibition of transcription.

PMID- 11964605
TI  - Effects of halothane and sevoflurane on inhibitory neurotransmission to medullary
      expiratory neurons in a decerebrate dog model.
AB  - BACKGROUND: In canine expiratory bulbospinal neurons, 1 minimum alveolar
      concentration (MAC) halothane and sevoflurane reduced the glutamatergic
      excitatory drive at a presynaptic site and enhanced the overall gamma
      aminobutyric acid (GABA)-mediated inhibitory input. The authors investigated if
      this inhibitory enhancement was mainly caused by postsynaptic effects. METHODS:
      Two separate anesthetic studies were performed in two sets of decerebrate,
      vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic
      hyperoxia. The effect of 1 MAC halothane or sevoflurane on extracellularly
      recorded neuronal activity was measured during localized picoejection of the
      GABAA receptor agonist muscimol and the GABAA receptor antagonist bicuculline.
      Complete blockade of GABAA-mediated inhibition with bicuculline was used to
      assess the prevailing overall inhibitory input to the neuron. The neuronal
      response to muscimol was used to estimate the anesthetic effect on postsynaptic
      GABAA receptor function. RESULTS: Halothane at 1 MAC depressed the spontaneous
      activity of 12 expiratory neurons 22.2 +/- 14.8% (mean +/- SD) and overall
      glutamatergic excitation 14.5 +/- 17.9%. Overall GABA-mediated inhibition was
      enhanced 14.1 +/- 17.9% and postsynaptic GABAA receptor function 74.2 +/- 69.2%.
      Sevoflurane at 1 MAC depressed the spontaneous activity of 23 neurons 20.6 +/-
      19.3% and overall excitation 10.6 +/- 21.7%. Overall inhibition was enhanced 15.4
      +/- 34.0% and postsynaptic GABAA receptor function 65.0 +/- 70.9%. The effects of
      halothane and sevoflurane were not statistically different. CONCLUSION: Halothane
      and sevoflurane at 1 MAC produced a small increase in overall inhibition of
      expiratory premotor neuronal activity. The increase in inhibition results from a
      marked enhancement of postsynaptic GABAA receptor function that is partially
      offset by a reduction in presynaptic inhibitory input by the anesthetics.

PMID- 11964606
TI  - An isolated, antegrade, perfused, peroneal nerve anterior tibialis muscle model
      in the rat: a novel model developed to study the factors governing the time
      course of action of neuromuscular blocking agents.
AB  - BACKGROUND: A model of an antegrade, perfused, isolated rat peroneal nerve
      anterior tibial muscle was developed to study potentially important factors
      governing the time course of action of (nondepolarizing) neuromuscular blocking
      agents such as concentration, blood flow, and temperature. The model allows
      observation of the effects of selective changes in these factors. METHODS: The
      authors isolated the anterior tibial muscle and cannulated the anterior tibial
      artery and vein, providing a way for single-pass perfusion with blood from a
      donor rat. A force transducer was connected to the tibialis anterior muscle and a
      stimulator was connected to the tibial nerve. The influence of intrinsic potency
      (EC90) and muscle blood flow rate on the time course of pancuronium and
      rocuronium was investigated. RESULTS: The model remained stable for at least 4 h
      with respect to twitch height, muscle structure and function, and blood
      chemistry. Doubling the muscle-blood flow resulted in a significantly faster
      onset and offset for both pancuronium and rocuronium. Trebling the intrinsic
      potency (EC90) was not associated with significant changes in the time course of
      action of the relaxants. CONCLUSION: The authors developed and validated a model
      that allows us to study biophase kinetics of neuromuscular blocking agents in the
      anterior tibial muscle of the rat. In this model, muscle-blood flow rather than
      EC90 appears to predominantly determine the onset and offset time of
      nondepolarizing muscle relaxants.

PMID- 11964607
TI  - Accelerated arteriolar gas embolism reabsorption by an exogenous surfactant.
AB  - BACKGROUND: Cerebrovascular gas embolism can cause profound neurologic
      dysfunction, and there are few treatments. The authors tested the hypothesis that
      an exogenous surfactant can be delivered into the bloodstream to alter the air
      blood interfacial mechanics of an intravascular gas embolism and produce bubble
      conformations, which favor more rapid bubble absorption. METHODS: Microbubbles of
      air were injected into the rat cremaster microcirculation after intravascular
      administration of either saline (control, n = 5) or Dow Corning Antifoam 1510US
      (surfactant, n = 5). Embolism dimensions and dynamics were directly observed
      after entrapment using intravital microscopy. RESULTS: To achieve embolization,
      the surfactant group required twice as many injections as did controls (3.2 +/-
      1.3 vs. 1.6 +/- 0.9; P < 0.05). There was no difference in the initial lodging
      configuration between groups. After bubble entrapment, there was significantly
      more local vasoconstriction in the surfactant group (24.2% average decrease in
      diameter) than in controls (3.4%; P < 0.05). This was accompanied by a 92.7%
      bubble elongation in the surfactant group versus 8.2% in controls (P < 0.05).
      Embolism shape change was coupled with surfactant-enhanced breakup into multiple
      smaller bubbles, which reabsorbed nearly 30% more rapidly than did parent bubbles
      in the control group (P < 0.05). CONCLUSIONS: Intravascular exogenous surfactant
      did not affect initial bubble conformation but dramatically increased bubble
      breakup and rate of reabsorption. This was evidenced by both the large shape
      change after entrapment and enhancement of bubble breakup in the surfactant
      group. These dynamic surfactant-induced changes increase the total embolism
      surface area and markedly accelerate bubble reabsorption.

PMID- 11964608
TI  - Does the immobilizing effect of thiopental in brain exceed that of halothane?
AB  - BACKGROUND: Recent studies suggest that anesthetics such as isoflurane act in the
      spinal cord to suppress movement that occurs during noxious stimulation. The
      authors examined the effect of halothane and thiopental on suppression of noxious
      evoked movement using a model of differential anesthetic delivery. They
      hypothesized that halothane and thiopental, similar to isoflurane, would suppress
      movement primarily via an action in spinal cord. METHODS: Goats were anesthetized
      and prepared for differential anesthetic delivery. Anesthesia was maintained with
      halothane (n = 5) or thiopental (n = 5). Anesthetic requirements were determined
      (noxious clamp on a dewclaw for 1 min) during halothane or thiopental (via
      infusion) delivery to the whole body and delivery only to the head. RESULTS:
      Control (whole body) halothane requirement was 0.9 +/- 0.2%; halothane
      requirement in the head during differential delivery was 3.4 +/- 1% (P < 0.01).
      During selective halothane delivery, the electroencephalogram was greatly
      depressed or was isoelectric even though the animals moved during noxious
      stimulation. Control (whole body) plasma thiopental requirement was 20 +/- 10
      microg/ml. When thiopental was selectively delivered to the head, the
      electroencephalogram was active in all five animals, and cranial thiopental
      requirement was 42 +/- 6 microg/ml (P < 0.01). CONCLUSION: These data suggest
      that halothane and thiopental, like isoflurane, act in spinal cord to suppress
      movement occurring with noxious stimulation. However, halothane appears to be
      less potent in the brain as evidenced by the electroencephalogram data,
      suggesting that action in spinal cord plays a more significant role for halothane
      than for thiopental.

PMID- 11964609
TI  - Droperidol inhibits GABA(A) and neuronal nicotinic receptor activation.
AB  - BACKGROUND: Droperidol is used in neuroleptanesthesia and as an antiemetic.
      Although its antiemetic effect is thought to be caused by dopaminergic
      inhibition, the mechanism of droperidol's anesthetic action is unknown. Because
      gamma-aminobutyric acid type A (GABAA) and neuronal nicotinic acetylcholine
      receptors (nAChRs) have been implicated as putative targets of other general
      anesthetic drugs, the authors tested the ability of droperidol to modulate these
      receptors. METHODS: gamma-Aminobutyric acid type A alpha1beta1gamma2 receptor,
      alpha7 and alpha4beta2 nAChRs were expressed in Xenopus oocytes and studied with
      two-electrode voltage clamp recording. The authors tested the ability of
      droperidol at concentrations from 1 nm to 100 microm to modulate activation of
      these receptors by their native agonists. RESULTS: Droperidol inhibited the GABA
      response by a maximum of 24.7 +/- 3.0%. The IC50 for inhibition was 12.6 +/- 0.47
      nm droperidol. At high concentrations, droperidol (100 microm) activates the
      GABAA receptor in the absence of GABA. Inhibition of the GABA response is
      significantly greater at hyperpolarized membrane potentials. The activation of
      the alpha7 nAChR is also inhibited by droperidol, with an IC50 of 5.8 +/- 0.53
      microm. The Hill coefficient is 0.95 +/- 0.1. Inhibition is noncompetitive, and
      membrane voltage dependence is insignificant. CONCLUSIONS: Droperidol inhibits
      activation of both the GABAA alpha1beta1gamma2 and alpha7 nAChR. The submaximal
      GABA inhibition occurs within a concentration range such that it might be
      responsible for the anxiety, dysphoria, and restlessness that limit the clinical
      utility of high-dose droperidol anesthesia. Inhibition of the alpha7 nAChR might
      be responsible for the anesthetic action of droperidol.

PMID- 11964610
TI  - Systematic review and analysis of postdischarge symptoms after outpatient
      surgery.

PMID- 11964611
TI  - Practice guidelines for sedation and analgesia by non-anesthesiologists.

PMID- 11964612
TI  - Postdural puncture upper back pain as an atypical presentation of postdural
      puncture symptoms.

PMID- 11964613
TI  - Altered level of consciousness after combined spinal-epidural labor analgesia
      with intrathecal fentanyl and bupivacaine.

PMID- 11964614
TI  - Iliopsoas abscess and persistent radiculopathy: a rare complication of continuous
      infusion techniques of epidural anesthesia.

PMID- 11964615
TI  - Delayed emergence and St. John's wort.

PMID- 11964616
TI  - Acute brain fat embolization occurring after total hip arthroplasty in the
      absence of a patent foramen ovale.

PMID- 11964617
TI  - Paradoxical cerebral fat embolism: an unusual cause of persistent unconsciousness
      after orthopedic surgery.

PMID- 11964618
TI  - Too limited a view of what clinical anesthesiology could become.

PMID- 11964619
TI  - Versatility of LMA-ProSeal for probe-passage.

PMID- 11964620
TI  - Local administration of morphine for analgesia after iliac bone graft harvest.

PMID- 11964621
TI  - Suggesting an alternative to the term "double-blind".

PMID- 11964622
TI  - Common substrates for pain and analgesia.

PMID- 11964625
TI  - The chirurgical works of Percivall Pott, F.R.S., surgeon to St. Bartholomew's
      Hospital, a new edition, with his last corrections. 1808.

PMID- 11964626
TI  - General principles of osteoarticular tuberculosis.
AB  - Since approximately 1985, with the pandemic of the human immunodeficiency virus
      and with the increase in the number of people who are immunocompromised, there is
      a resurgence of tuberculosis worldwide. The diagnosis in endemic areas generally
      can be made on clinical and radiologic examinations. However, whenever there is
      doubt because of an atypical clinical presentation or lack of clinical exposure,
      tissue diagnosis is mandatory. If osteoarticular tuberculosis is diagnosed and
      treated at an early stage, approximately 90% to 95% of patients would achieve
      healing with near normal function. The mainstay of treatment is multidrug
      antituberculous chemotherapy (for 12 to 18 months) and active - assisted non
      weightbearing exercises of the involved joint throughout the period of healing.
      Operative intervention is required when the patient is not responding after 4 to
      5 months of chemotherapy (synovectomy and debridement), the therapeutic outcome
      is not satisfactory (excisional arthroplasty for the hip or the elbow), or the
      healed status has resulted in a painful ankylosis (arthrodesis for the ankle, the
      wrist, or the knee). Joint replacement may be considered if the disease has
      remained inactive for 10 years or more. Multidrug resistance should be suspected
      if the activity of disease does not subside after 4 to 6 months of uninterrupted
      multidrug therapy. Such patients (5% to 10%) present a desperate therapeutic
      challenge. Second-line and potential antitubercular drugs, and possible
      immunomodulations may control such a disease.

PMID- 11964627
TI  - Chemotherapy for osteoarticular tuberculosis.
AB  - Chemotherapy for tuberculosis in general and osteoarticular tuberculosis in
      particular poses certain peculiar problems that include chronicity of infection,
      infection by resistant mycobacteria, persistent mycobacteria, possibility of
      concomitant human immunodeficiency virus infection, and drug toxicity during
      prolonged treatment. Although the success rate of chemotherapy is greater than
      90% with optimum drug combination regimens currently used, there is a need for
      additional improvement. A successful outcome depends on using an optimum regimen,
      which contains safer and more effective drugs given regularly for an adequate
      period. The most important cause of treatment failure is poor patient compliance,
      which can be improved by using supervised drug treatment programs. In a few
      patients, surgical removal of infected tissue may be indicated to improve the
      efficacy of chemotherapy. In the future, safer and more effective
      antimycobacterial and anti-acquired immunodeficiency syndrome drugs may become
      available. Research in various related fields also is expected to additionally
      improve prophylaxis and treatment.

PMID- 11964628
TI  - Human immunodeficiency virus and osteoarticular tuberculosis.
AB  - The human immunodeficiency virus pandemic has contributed to a marked increase in
      patients infected with tuberculosis. In parts of SubSaharan Africa,
      osteoarticular tuberculosis has increased fourfold in the past decade and
      approximately 60% of the patients are infected with the human immunodeficiency
      virus. The human immunodeficiency virus has complicated the diagnostic process
      and treatment. Tuberculosis will respond to chemotherapy in patients who are
      positive for the human immunodeficiency virus but adverse drug reactions are
      common. Careful assessment is necessary if surgery is contemplated because of the
      high risk of infection and poor wound healing in patients with advanced human
      immunodeficiency virus disease. In patients with osteoarticular tuberculosis who
      are positive for human immunodeficiency virus, the prognosis will depend on the
      stage that the human immunodeficiency virus infection has reached by the time of
      presentation.

PMID- 11964629
TI  - Imaging of musculoskeletal tuberculosis: a new look at an old disease.
AB  - There are certain imaging features that help to differentiate tuberculosis from
      other bone and joint disorders with a similar presentation. The current authors
      discuss these distinguishing imaging features particularly with respect to
      ultrasound, computed tomography, and magnetic resonance imaging. The judicious
      and appropriate use of these newer imaging modalities coupled with aspiration or
      biopsy can lead to earlier recognition of musculoskeletal tuberculosis before the
      onset of debilitating disease.

PMID- 11964630
TI  - Conservative treatment of tuberculosis of the lumbar and lumbosacral spine.
AB  - Fifty-six adults (average age, 38 years) with active tuberculosis of the lumbar
      and lumbosacral spine were treated conservatively with triple chemotherapy for 12
      to 18 months. The minimum followup was 3 years. Three methods of assessments of
      the chronologic changes of sagittal spinal deformity were used on lateral
      radiographs of the lumbar spine obtained with the patient standing: deformity,
      kyphos angles, and total lumbar lordosis. The lumbosacral joint angle was
      measured for tuberculosis of the lumbosacral joint. The disease healed in all
      patients with a minimum increase of kyphosis, although in 23 patients there was
      minimal new involvement of the adjacent vertebral bodies within 6 months of
      treatment. The pattern of the involved vertebral body collapse in tuberculosis of
      the lumbar and lumbosacral joints was vertical (telescoping), along a
      longitudinal axis that minimized the progression of kyphosis. The outcome was
      judged on the basis of residual kyphosis (British Medical Research Council
      criteria) and found to be favorable in 96.4% (54 patients). Triple chemotherapy
      for lumbar and lumbosacral tuberculosis is effective in curing the disease and in
      minimizing the residual kyphosis through early diagnosis and immediate initiation
      of chemotherapy. The pattern of vertebral body collapse is the telescoping type,
      which is the determining factor in minimizing residual spinal deformity.

PMID- 11964632
TI  - The outcome of allografts and anterior instrumentation in spinal tuberculosis.
AB  - Spinal tuberculosis is the most common form of osteoarticular tuberculosis.
      Fractures, slippage, and increasing deformity have been reported with the use of
      autologous rib grafts after anterior spinal decompression. Forty-one patients
      with neurologic deficits caused by spinal tuberculosis had radical anterior
      decompression, and the anterior column was reconstructed with fresh-frozen
      femoral allografts and stabilized with a single-rod screw construct.
      Antituberculous therapy was administered for 12 months and complete neurologic
      recovery occurred in 32 patients. The incorporation of allografts commenced
      between 12 and 18 months. Fusion and remodeling was observed in 33 patients and
      partial remodeling with fusion was observed in eight patients at a mean followup
      of 6.4 years. Forty-two percent correction of the kyphosis was achieved and there
      were no cases of fracture or late sepsis. Fresh-frozen allografts and anterior
      instrumentation are superior to rib grafts in supporting the anterior spinal
      column, and although fusion occurred late, the grafts remained stable.

PMID- 11964631
TI  - Combined anterior and posterior surgeries in the treatment of spinal tuberculous
      spondylitis.
AB  - Methods for the treatment of tuberculous spondylitis still are controversial. The
      authors treated 32 consecutive patients with a two-stage surgical technique
      combined with antituberculous chemotherapy for 1 year. After anterior
      debridement, fusion with autogenous anterior iliac tricortical strut bone graft
      was done, and in a second stage, posterior instrumentation and fusion with
      autogenous posterior iliac corticocancellous bone graft was done 11 days (range,
      4-22 days) later. Postoperatively, patients were encouraged to ambulate with
      brace protection as early as possible. Twenty-nine patients were followed up for
      a minimum of 2 years (median, 4.7 years; range, 2-10 years) of whom 28 patients
      achieved solid fusion (97%). All patients had improvement of back pain including
      the only patient with pseudarthrosis. Neurologic deficits completely recovered in
      84% (16 of 19) of patients after 3 months. Kyphotic deformity improved in all 29
      patients (34.6 degrees versus 17.3 degrees ) with the average correction angle of
      17.3 degrees. Clinically, 27 patients had achieved a satisfactory outcome (93%).
      There were no evident surgical complications. The authors, therefore, recommend a
      two-stage surgical technique combined with antituberculous chemotherapy to treat
      patients with severe vertebral body destruction attributable to tuberculosis
      because of its high success rate and a low complication rate.

PMID- 11964633
TI  - Atypical spinal tuberculosis.
AB  - Typical spinal tuberculosis is readily diagnosed and treated. Certain atypical
      clinical and radiologic presentations of spinal tuberculosis are described.
      Failure to recognize these presentations may lead to delay in diagnosis and
      initiation of treatment. In some atypical forms of the disease, this may have
      disastrous consequences. The current authors present a new classification for
      atypical spinal tuberculosis and describe the various presentations. The role of
      advanced imaging studies such as computed tomography scanning and magnetic
      resonance imaging and imaging-guided aspiration cytology is discussed.

PMID- 11964634
TI  - Treatment of tuberculosis of the spine with neurologic complications.
AB  - Neurologic complications are the most dreaded complication of spinal
      tuberculosis. The patients who have paraplegia develop in the active stage of
      tuberculosis of the spine require active treatment for spinal tuberculosis and
      have a better prognosis than the patients who have paraplegia develop many years
      after the initial disease has healed. Neurologic dysfunctions in association with
      active tuberculosis of the spine can be prevented by early diagnosis and prompt
      treatment. Prompt treatment can reverse paralysis and minimize the potential
      disability resulting from Pott's paraplegia. When needed, a combination of
      conservative therapy and surgical decompression yields successful results in most
      patients with tuberculosis of the spine who have neurologic complications. The
      vertebral body primarily is affected in tuberculosis; therefore, decompression
      has to be anterior. Laminectomy is advocated in patients with posterior complex
      disease and spinal tumor syndrome. Late onset paraplegia is best avoided by
      prevention of the development of severe kyphosis. Patients with tuberculosis of
      the spine who are likely to have severe kyphosis develop (< 60 degrees) on
      completion of treatment should have surgery in the active stage of disease to
      improve kyphus.

PMID- 11964635
TI  - The problem of deformity in spinal tuberculosis.
AB  - Spinal tuberculosis is the most common cause for a kyphotic deformity in patients
      in many parts of the world. There is an average increase of 15 degrees deformity
      in all patients who are treated conservatively and 3% to 5% of patients may end
      up with a deformity that is greater than 60 degrees. The progress of deformity
      occurs in two distinct phases: Phase I, which includes the changes in the active
      phase, and Phase II, which includes changes after the disease is cured. The
      progress of deformity is influenced by the severity of the angle before
      treatment, the level of the lesion, and age of the patient. Adults have an
      increase less than 30 degrees during the active phase with no additional change.
      Children, in contrast, have significant changes even in the healed phase of the
      disease. During the growth spurt, there is worsening of the deformity in 39%
      (Type I progression), an improvement in 44% (Type II), and no change in 17% (Type
      III). Children at risk of late progressive deformity can be identified early by
      the presence of spine-at-risk radiologic signs. Surgery for preventing deformity
      must be done earlier rather than later and in patients with severe disease,
      stabilization by the use of posterior and anterior instrumentation is necessary
      to obtain a good outcome.

PMID- 11964636
TI  - Tuberculosis of the hip.
AB  - Tuberculosis of the hip constitutes approximately 15% of all cases of
      osteoarticular tuberculosis. The common age of presentation is in the second and
      third decades. In Stages II and III of the disease, the radiologic features are
      very obvious and diagnostic, and almost always predict the final clinical
      outcome. A progressive pattern of destruction of the hip occurs in patients who
      are not treated. Treatment must be instituted early with an aim of salvaging the
      hip. Treatment comprised of drug therapy, traction, and supervised mobilization
      produces good results in patients with early stages of the disease. Patients who
      do not have a favorable clinical response to conservative treatment should have
      surgery before the hip is destroyed. In the eastern hemisphere, patients prefer a
      painless but mobile joint, for satisfying the customary needs of squatting,
      sitting cross-legged, and kneeling. Therefore, excision arthroplasty produces
      satisfactory results as compared with hip arthrodesis. Total hip arthroplasty
      should be considered only after a safe period of absolute disease quiescence.

PMID- 11964637
TI  - Tuberculosis of the knee.
AB  - Fifty-two children with tuberculosis of the knee treated from 1979 to 1999 were
      reviewed retrospectively. The radiologic appearance of the joint at presentation
      was predictive of the outcome. Ninety-two percent of the patients had Stage 1 or
      Stage 2 involvement (synovitis) with or without bony erosions, but had a normal
      joint space. Treatment with antituberculous chemotherapy without synovectomy had
      an excellent or good result in all patients with Stage 1 or Stage 2 disease, and
      there was no difference in outcome whether the knee was immobilized or mobilized.
      Patients with Stage 3 and Stage 4 disease who had a narrow joint space
      (arthritic) at presentation had a fair or poor result. In patients with
      monoarthritis of the knee with nonspecific histologic features and a negative
      culture, the differential diagnosis between tuberculosis and pauciarticular
      juvenile rheumatoid arthritis is problematic. The histologic evaluations of
      biopsy specimens of the synovium of 25 knees from 25 patients were reviewed for
      synovial lining hyperplasia. The sensitivity for the 17 knees that subsequently
      were diagnosed as having juvenile rheumatoid arthritis was only 53%.
      Deoxyribonucleic acid from 13 consecutive joints was subjected to polymerase
      chain reaction for Mycobacterium tuberculosis infection with only 40% sensitivity
      for tuberculosis.

PMID- 11964639
TI  - Unusual manifestations of osteoarticular tuberculosis.
AB  - Unusual manifestations of osteoarticular tuberculosis, especially tubercular
      osteomyelitis, are described. Diagnostic problems may arise and lead to delay in
      treatment if these conditions are not considered in the differential diagnosis.
      The importance of bacteriologic and histopathologic confirmation of the disease
      is stressed.

PMID- 11964638
TI  - Tuberculosis of the foot and ankle.
AB  - Tuberculosis of the foot and ankle is an uncommon presentation of skeletal
      tuberculosis. The uncommon site, lack of awareness, and ability to mimic other
      disorders clinically and on radiographs, leads to diagnostic and therapeutic
      delays. In the early stages and when the disease is limited to bone, medical
      treatment leads to excellent healing and limited residual disabilities. Joint
      involvement occurs because of spread from a periarticular bony focus, and in the
      midfoot, the disease may spread to involve all the interconnected joints, leading
      to a stiff foot and residual deformities. Of 74 cases reviewed, the calcaneus was
      involved most commonly, followed by infection of the midtarsal, Lisfranc joints,
      and ankle. The most common radiologic finding is that of osteoporosis, which may
      be intense: cancellous bone involvement may present as a cystic lesion with or
      without sequestrum. Computed tomography scans and magnetic resonance imaging are
      helpful examinations. Because the disease is paucibacillary, a positive acid fast
      bacilli culture is rare and the diagnosis usually is confirmed by obtaining
      granulomatous tissue on biopsy. The treatment basically is medical, with surgical
      intervention being reserved for patients with intractable disease or as a salvage
      procedure for patients with deformed hindfoot joints.

PMID- 11964640
TI  - Anterior shoulder instability: histomorphometric study of the subscapularis and
      deltoid muscles.
AB  - Recurrent traumatic anterior shoulder dislocation results in soft tissues lesions
      around the glenohumeral joint. The subscapularis muscle is a major active
      stabilizer of the shoulder and the hypothesis of the current study is that one
      would expect pathologic changes within its substance secondary to the trauma. A
      histomorphometric study of the subscapularis muscle was done of 52 patients
      operated on for recurrent traumatic anterior shoulder dislocation. At the time of
      surgery biopsy specimens were taken of the subscapularis muscle and the
      ipsilateral deltoid muscle as a comparison and to see if any changes were
      present. The results revealed interstitial fibrosis within the subscapularis
      muscle compatible with muscle scarring, and modifications in the ratio of fiber
      types as usually is seen with disuse atrophy. Both of these findings may alter
      strength and stability and therefore the function of the glenohumeral joint. The
      histologic findings were not compatible with a denervation pattern. After
      traumatic anterior shoulder dislocation rehabilitation of the subscapularis
      muscle is recommended.

PMID- 11964641
TI  - Local injection treatment for lateral epicondylitis.
AB  - In a prospective randomized study of lateral epicondylitis, 120 patients were
      treated with 2 mL lidocaine (Group A, n=60) or 1 mL lidocaine combined with 1 mL
      triamcinolone (Group B, n=60). All injections were done using the peppering
      technique: after inserting the needle the tender area was peppered with 40 to 50
      injections by injecting, withdrawing, redirecting, and reinserting without
      emerging from the skin. All patients were followed up for 1 year. Fifty-six
      patients in Group A and 57 patients in Group B had excellent results. There was
      statistically no difference between the groups. Both groups had excellent results
      and because the injection of local anesthetics is known to have no long-term
      effect in the treatment of lateral epicondylitis, the peppering technique seems
      to be a reliable method of treatment.

PMID- 11964642
TI  - Effect of lumbar disc herniation on clinical symptoms in lateral recess syndrome.
AB  - This study investigated the differences in the clinical features of lateral
      recess syndrome attributable to the bony entrapment of the spinal nerve root
      under the superior articular facet, and lateral recess syndrome and associated
      lumbar disc herniation. Ninety patients with pure bony entrapment (47 men, 43
      women) ranging in age from 19 to 83 years (mean age, 63 years) and 59 patients
      with lumbar disc herniation in the lateral recess (43 men, 16 women) 19 to 85
      years of age (mean age, 49 years) were included in this study. All patients had
      L5 root radiculopathies and were treated surgically. Although the early symptoms
      of patients with lateral recess syndrome often were in the lower extremities,
      many of the patients with associated lumbar disc herniation had a transition
      initially experiencing low back pain and subsequently having lower extremity
      symptoms. Flexion and extension of the lumbar spine exacerbated symptoms,
      particularly in patients with lumbar disc herniation. The results of the current
      study show that the clinical presentation of lateral recess syndrome differs
      depending on the cause of the compression in the lateral recess.

PMID- 11964643
TI  - Revision surgery in pelvic discontinuity: an analysis of seven patients.
AB  - The technical aspect and clinical outcome of seven patients with pelvic
      discontinuities in acetabular revision surgery after a mean followup of 96 months
      were analyzed. The surgical treatment consisted of three consecutive steps
      beginning with mechanical stabilization of the two acetabular columns, followed
      by bony acetabular reconstruction by filling the osteolytic defect with allograft
      chips covered with autologous bone to achieve a contained defect after healing of
      the autograft, and anchorage of the cup using an acetabular reinforcement ring
      (five with a hook, two without a hook). Complications included a partial ischial
      nerve lesion, one intraoperative femoral shaft fracture, and one recurrent
      dislocation. One patient had revision surgery 12 months after the first revision
      surgery because of aseptic loosening, and in one patient two prominent screws had
      to be removed. The clinical improvement according to the Harris hip score was
      40.1 points on average (preoperative, 33 points; postoperative, 73.1 points). At
      the final followup all acetabular components were stable and the pelvic
      discontinuity had healed. Despite the technical feasibility of such revisions and
      the acceptable clinical results, the complication rate is high. Early diagnosis
      of acetabular loosening to minimize the osteolytic loss of bone stock is
      important.

PMID- 11964644
TI  - Collar versus collarless cemented HD-II femoral prostheses.
AB  - A randomized prospective study was done in 1982 to evaluate the effect of a
      collar on the cemented femoral component. During a 2-year period, 84 patients
      were enrolled to receive a collared (44 hips) or a collarless (40 hips) HD-II
      femoral component at the time of their primary total hip arthroplasty. Three
      patients were lost to followup, two patients were excluded because of
      randomization errors, six patients had good clinical results but refused
      followup, and 30 patients had died. The 43 surviving patients (collar 24,
      collarless 19) had radiographic and clinical followups at an average of 9.6 years
      (range, 61-143 months). Harris hip scores were similar, with an average of 89 in
      the collared group and 78 in the collarless group. There were no differences in
      the incidence or magnitude of pain between the patients receiving a collared or
      collarless femoral component. The Kaplan-Meier survivorship analysis predicted an
      overall survival rate free of revision of 86% at 10 years. There were no
      statistically significant differences in survival rates between the two groups.

PMID- 11964645
TI  - Fat embolism after uncemented total hip arthroplasty.
AB  - The authors present a 59-year-old woman who had a severe fat embolism syndrome
      develop after an uncemented total hip arthroplasty. The fat embolism syndrome was
      confirmed by clinical, laboratory, and imaging findings. The patient had a
      favorable outcome most likely related to early supportive therapy, her healthy
      background, and young age.

PMID- 11964647
TI  - Two-stage reconstruction with autografts for knee dislocations.
AB  - Traumatic knee dislocations are severe injuries that involve damage to the
      anterior cruciate ligament, the posterior cruciate ligament, and the lateral or
      medial ligamentous structures. There are no established methods of treatment. The
      objective of the current study was to report the clinical outcome of a two-stage
      autologous reconstruction on nine knees (eight patients). The mean followup was
      40.1 months. The first stage of the reconstruction was done at a mean of 2 weeks
      after the injury, and the posterior cruciate ligament was reconstructed by an
      arthroscopically assisted technique using contralateral autogenous hamstring
      tendon as the graft material. Three months later, the second stage of the
      reconstruction was done for the ligaments that had not healed with conservative
      treatment. Arthroscopically assisted anterior cruciate ligament reconstruction
      was done on all of the knees using the ipsilateral autogenous hamstring tendon or
      bone-patellar tendon-bone as the graft material. At the same time, a medial
      collateral ligament reconstruction using an autogenous semitendinosus tendon was
      done on one knee, and reconstruction of the posterolateral ligamentous structures
      using a biceps tendon was done on three knees. Each of the knees that was
      reconstructed was capable of full extension, and the mean degree of passive
      flexion was 139.5 degrees +/- 5.2 degrees. The mean side-to-side difference in
      anteroposterior total laxity (KT-1000 arthrometer, manual maximum) was 2.3 +/-
      1.9 mm. None of the knees had lateral or medial instability. All of the injured
      ligaments were able to be reconstructed with autografts, and severe contracture
      was able to be prevented. A good clinical outcome can be achieved when two-stage
      reconstruction is used for traumatic knee dislocations.

PMID- 11964646
TI  - Force reduction by an external hip protector on the human hip after falls.
AB  - This is the first quantitative study of the impact force over the hips of
      volunteers who fell laterally from standing to a hard surface while wearing a hip
      protector. Protector pads were first tested with a drop weigh machine.
      Piezoelectric sensors were placed on the impact surface to record force-time
      curves with and without a pad covering the surface. Two types of pads transmitted
      only 9% of the force at a drop weight impact force of 13,372 N. Sensors were
      placed over the hip under a protective hip pad worn by 10 volunteers who
      deliberately fell from standing, to a concrete surface. Only 5% or less impact
      force was transmitted to the skin sensors, and no hip injuries occurred after 85
      falls, providing evidence for the safety of such falls. Only transient skin pain
      and tenderness occurred in three volunteers. Force transmission through the pads
      was well below that required to fracture hips from cadavers with osteoporosis in
      vitro. There was variability in the reduction of force transmission among the
      volunteer subjects. A 1-month compliance study with 106 elderly subjects showed
      protector use for 70% to 95% of their hours out of bed.

PMID- 11964648
TI  - Knee extensor mechanism reconstruction with medial gastrocnemius flap.
AB  - Infection after osteotomy of the tibial tubercle can lead to nonunion and chronic
      osteomyelitis of the tuberosity. Radical debridement for control of infection in
      this situation may require resection of the sequestrated tuberosity fragment with
      the resultant problem of disruption of the extensor mechanism of the knee. A
      review of the literature failed to identify any description of successful
      treatment of such a complication. The case of a 28-year-old woman with this
      complication is reported. After resection of the sequestrated tibial tuberosity
      and sinus tract, the extensor mechanism was reconstructed with the medial
      gastrocnemius flap in a one-stage procedure. The infection was eradicated
      successfully and excellent knee function was restored. The technique and 5-year
      result are presented.

PMID- 11964649
TI  - Septic arthritis in postoperative anterior cruciate ligament reconstruction.
AB  - A review of postoperative infected anterior cruciate ligament reconstructions was
      done on 3500 consecutive arthroscopic procedures. The purpose was to assess
      incidence, diagnosis, treatment, and outcome factors. Six postoperative
      intraarticular infections were detected. Average followup was 3 years (range, 2-8
      years). The rate of infection was 0.14%. Five men and one woman with a median age
      of 32.5 years (range, 20-51 years) comprised the study group. The average
      interval from the onset of symptoms to the initial arthroscopic intervention was
      7.5 days (range, 2-20 days). Staphylococcus aureus was present in three knees,
      Staphylococcus epidermidis in two, and Streptococcus nonhemolytic in one. All
      patients had initial arthroscopic debridement and lavage followed by 6 weeks of
      intravenous antibiotics. Two grafts were removed: one patient had delayed
      ligament reconstruction and the other had total knee arthroplasty. The remaining
      patients had full range of motion. In the group with the best result, two
      patients had Staphylococcus epidermidis and one had Staphylococcus aureus, which
      was treated 2 days after clinical symptoms began. The other two patients infected
      with Staphylococcus aureus had unsatisfactory results. Anterior cruciate ligament
      infection is rare, but diagnosable. When treated early with appropriate
      antibiotic therapy and arthroscopic debridement, four of six grafts were
      retained. If the infection does not respond rapidly to early therapy, then graft
      removal is an option.

PMID- 11964650
TI  - Muscle torques in total knee arthroplasty with subvastus and parapatellar
      approaches.
AB  - The current study was designed to compare muscle torques when using the subvastus
      and parapatellar approaches for unilateral total knee arthroplasty. Twelve female
      patients had unilateral total knee arthroplasty with the subvastus approach from
      January 1997 to June 1998. The historic control group consisted of 16 female
      patients who had unilateral total knee arthroplasty with the parapatellar
      approach from July 1994 to January 1997. Six and 12 months after surgery, a Cybex
      dynamometer was used to measure isometric and isokinetic muscle strength. Two
      parameters were used to compare the two approaches, the first parameter was the
      difference in peak torque between the surgically treated knee and the baseline
      value for the healthy knee, and the second parameter was the hamstring to
      quadriceps peak-torque ratio, again using the value for the healthy knee as
      baseline. The subvastus approach resulted in an initial higher peak torque in the
      quadriceps 6 months after surgery, but this difference became insignificant 12
      months postoperative. Using the subvastus approach, the hamstring to quadriceps
      peak-torque ratio reached the normal range (0.50-0.80) sooner than was the case
      using the parapatellar approach. There is a phenomenon of cross adaptation of the
      untreated knee to the surgically treated knee, and knees operated on by the
      subvastus approach showed functional recovery at an earlier date than those
      operated on by the parapatellar approach.

PMID- 11964651
TI  - Significance of talar distortion for ankle mobility in idiopathic clubfoot.
AB  - The abnormal bony feature found most consistently in clubfeet is talar
      distortion. The significance of the talar distortion for mobility of the
      tibiotalar joint was investigated. Twenty-seven congenital clubfeet in 19
      patients were examined at a minimal followup of 20 years. In all patients Turco's
      posteromedial release was done because of idiopathic clubfoot. Radiographic
      assessment of the feet included measurement of the talocalcaneal angle and index,
      and the tibiocalcaneal angle. The degree of talar flattening was estimated by the
      ratio of the curvature of the talar dome to the length of the talar bone (radius
      to length ratio). Three-dimensional gait analysis was done to assess the dynamic
      range of ankle motion. The static range of motion was measured with a goniometer.
      The degree of talar flattening correlated significantly with the dynamic range of
      ankle motion but not with the static mobility. For assessment of idiopathic
      clubfoot, evaluation of talar flattening should be done because of its
      significance for dynamic ankle mobility.

PMID- 11964652
TI  - Atypical lipomatous masses of the extremities: outcome of surgical treatment.
AB  - Atypical lipomatous tumors occur predominantly in middle-aged patients and often
      present as painless, slow-growing masses in the extremities. The clinical
      outcomes of surgically treated superficial or deep atypical lipomas of the
      extremities were reviewed. Thirty-one patients were included in this study. There
      were 16 men and 15 women, with an average age of 57 years (range, 32-87 years).
      The mean followup was 7 years (range, 1-28.8 years). Twenty-five tumors occurred
      in the lower extremity and six in the upper extremity. Sixteen patients (52%) had
      a recurrence at an average of 4.7 years after resection. Twelve (39%) patients
      required additional surgical procedures to treat their tumor. Occurrence of a
      deep lesion and positive margins at the time of the initial surgery correlated
      closely with the rate of recurrence and need for additional surgical treatment.
      Dedifferentiation to high-grade liposarcoma developed in four (13%) patients.
      Atypical lipomas have a high propensity for local recurrence and a potential for
      malignant dedifferentiation. Patients with atypical lipomas require careful
      evaluation, complete surgical excision when possible, and close clinical followup
      extending beyond 5 years.

PMID- 11964653
TI  - Analysis of organ selectivity in the metastatic behavior of Dunn osteosarcoma.
AB  - In the current study, the authors established a novel metastatic model to analyze
      organ selective metastasis by osteosarcoma, using a murine cell line, Dunn
      osteosarcoma. The lung, liver, kidney, and spleen were resected from syngeneic
      donor mice, and a tissue fragment of the respective organs was transplanted
      subcutaneously into a recipient mouse. Two weeks later, tumor cells were injected
      intravenously and the formation of metastatic deposits in the ectopic transplants
      was examined. Ectopic lung transplants had a significantly higher incidence of
      metastasis than either liver or kidney transplants. When enzymatically dispersed
      organ cells that were embedded in agar gel were transplanted, intravenous
      injection of tumor cells also resulted in a higher metastatic rate in lung
      transplants than in either liver or kidney transplants. Photomicrographs and
      microangiographs of the transplants showed equivalent revascularization of the
      different organs. Radiolabeled tumor cells were deposited in equivalent amounts
      in the ectopic transplants of the different organs after intravenous injection.
      In addition, in vitro growth of tumor cells was stimulated by medium conditioned
      with lung tissue in a dose-dependent manner. These results suggest that organ
      selective metastasis by osteosarcoma is not defined anatomically or
      hemodynamically, but may be caused by tumor cells responding to possible
      paracrine factors emanating from the lung.

PMID- 11964654
TI  - Treatment of femoral diaphyseal nonunions.
AB  - There have been conflicting reports regarding treatment of femoral diaphyseal
      nonunions using reamed intramedullary nailing. Although high union rates have
      been reported using this technique, not all orthopaedic surgeons have experienced
      the same success. A retrospective review of charts and radiographs of 39 adult
      patients with nonunions of the femoral diaphysis treated at the authors'
      institution with reamed intramedullary nailing, compression, and with and without
      interlocking was done. The time from the index procedure to nonunion repair was 4
      to 75 months (average, 19 months). Fifteen patients had 18 procedures between the
      index operation and nonunion repair. The average followup from nonunion repair to
      the most recent examination was 22.5 months (range, 3-108 months) with a median
      of 15 months. At the last followup, the overall union rate was 74% after one
      procedure and 97% after two or more procedures. There were seven complications
      including two infections, one pulmonary embolus, one occurrence of a deep venous
      thrombosis, a hematoma, and one case of malrotation. The data support the use of
      antegrade reamed nailing as a successful technique for treatment of most femoral
      diaphyseal nonunions.

PMID- 11964655
TI  - Nonunion of nonoperatively treated fractures of the radial head.
AB  - Although fractures of the radial head traditionally are not associated with
      healing problems, delayed union and nonunion are being seen more frequently after
      operative and nonoperative treatment. Given the tenuous blood supply to the head
      of the radius, problems with healing are not surprising. As the current review of
      five patients with nonunion of nonoperatively treated radial head fractures
      treated during a 6-year period shows, healing problems rarely are symptomatic and
      often may go unrecognized. Even when the fracture still is apparent on
      radiographs obtained more than 1 year after the injury, healing still may occur.
      Operative treatment, although rarely necessary, achieved union in one of the
      current patients.

PMID- 11964656
TI  - Arterial vascularization of the proximal extensor carpi radialis brevis tendon.
AB  - The macroscopic arterial vascularization of the extensor carpi radialis brevis
      tendon was investigated in 12 elbows from cadavers to provide fundamental
      anatomic information of this tendon which has been associated with lateral
      epicondylitis. The arterial blood supply of the extensor carpi radialis brevis
      tendon was highly consistent. The radial recurrent artery vascularized the entire
      proximal tendon through direct branches to the medial and lateral border of the
      tendon forming a network of small vessels on the surface of the tendon. Important
      contributions were provided by the posterior branch of the radial collateral
      artery, and minor contributions were provided by the interosseous recurrent
      artery. The undersurface of the tendon seemed almost avascular. This observation
      suggests that potential hypovascular zones might be located at the undersurface
      of the tendon causing degeneration and partial tear of the tendon, and that this
      might be an etiologic factor in the pathogenesis of lateral epicondylitis.
      Additional microvascular studies are necessary to investigate this hypothesis.

PMID- 11964657
TI  - Extensor hallucis longus innervation: an anatomic study.
AB  - Thirty legs from skeletally mature embalmed cadavers were dissected to define the
      most common pattern and the variants of innervation of the extensor hallucis
      longus muscle and its clinical significance. Twenty-seven muscles had only one
      innervating branch (90%). Only three muscles had two innervating branches (10%).
      Twenty-one of the branches entered the muscles from the fibular side (63.6%), six
      entered the muscles from the tibial side (18.2%), and six entered the muscles
      from the anterior edge (18.2%). The branches innervating the extensor hallucis
      longus from the fibular side had a closer relation with the fibular periosteum
      than those entering the muscle from the tibial side or the anterior edge. The
      mean length of these branches between their points of origin and entry in the
      extensor hallucis longus was 5.0 +/- 1.5 cm. The high risk zone for the
      iatrogenic injury to the muscular branch of the extensor hallucis longus was
      located between 5.9 +/- 1.7 and 10.9 +/- 1.7 cm inferior to the most distal
      palpable point of the fibular head. The current study confirmed that the extensor
      hallucis longus was supplied mostly by one nerve that usually entered the muscle
      from the fibular side and had a close relation to the fibular periosteum in the
      dangerous zone.

PMID- 11964658
TI  - A computerized system for orthopaedic oncology.
AB  - For the past 15 years, the orthopaedic oncology service at the author's
      institution has used a computer system to aid in the treatment of patients. The
      system currently uses a DOS or at times a Windows-based program known as FOXPRO
      which originally was created by an independent company and now is part of the
      Microsoft systems. This presentation describes the components of this system and
      defines its use in patient treatment including demographics, office and surgical
      records, fiscal issues, and research.

PMID- 11964659
TI  - Shoulder mass in a 20-year-old man.

PMID- 11964660
TI  - Re: Ogden, et al. Shock wave therapy for chronic proximal plantar fasciitis. Clin
      Orthop 387:47-59,2001.

PMID- 11964662
TI  - Mast cells as orchestrators of the allergic reaction: the IgE-IgE receptor mast
      cell network.

PMID- 11964663
TI  - The nose-lung interaction in allergic rhinitis and asthma: united airways
      disease.
AB  - The link between upper and lower respiratory tracts has been repeatedly observed
      in the past 50 years but only carefully investigated during the past decade.
      Several clinical and experimental observations suggested the hypothesis of the
      unity of upper and lower airways (allergic rhinobronchitis or united airways
      disease). The relationships between rhinitis (and sinusitis) and asthma also
      include non-epidemiological aspects such as viral infections and bronchial
      hyperreactivity. The hypotheses have been confirmed by means of epidemiological
      observations, functional and immunological evidence and, indirectly, by observing
      the effects of drugs used mainly for rhinitis on asthma symptoms. In this
      article, therefore, we collected and reviewed the most relevant experimental
      results available to support the hypothesis for united airways disease and the
      studies conducted on the possible mechanisms of nose-lung interaction.

PMID- 11964664
TI  - Non-allergic rhinitis: diagnosis and management.
AB  - Patients in the rhinitis clinic with negative skin prick tests present a
      challenge. Non-allergic rhinitis consists of a variety of conditions including
      infection, hormonal changes, drugs and autonomic dysfunction. There is also a
      range of systemic disorders to be considered. The pathogeneses of many of these
      are less well understood than that of allergic rhinitis, diagnosis and treatment
      pathways are also more complex. A detailed accurate history needs to be taken
      followed by relevant investigations which may include allergen challenge, because
      skin prick and RAST-negative allergic rhinitis is now recognised. Nitric oxide
      levels may prove helpful: elevated levels suggest inflammation, very low levels
      indicate the possibility of primary ciliary dyskinesia or cystic fibrosis.
      Treatment is of the underlying cause when found: for those without obvious
      pathology a trial of combined therapy with topical corticosteroids plus
      antihistamine or plus anti-cholinergic may be worth while. A complex inter
      relationship between allergic and infectious rhinitis is becoming apparent.

PMID- 11964665
TI  - Viral rhinitis and asthma.
AB  - Upper respiratory tract infections are among the most common infectious diseases.
      Approximately 80% of the common colds are caused by rhinoviruses. Recently,
      rhinovirus colds have been linked with lower airway illnesses such as asthma
      exacerbations resulting in a considerable interest in the pathogenesis of lower
      respiratory tract pathology. The important role that allergic airway disease
      plays in virally induced changes in airway function has been experimentally shown
      in several studies. Unfortunately, the precise mechanisms by which viruses could
      induce lower airway symptoms have not yet been determined.

PMID- 11964666
TI  - Aspirin-induced rhinitis and asthma.
AB  - Interesting findings relating to aspirin-induced asthma recently emerged. In this
      distinct clinical syndrome, aspirin and most other nonsteroidal anti-inflammatory
      drugs that inhibit cyclooxygenase precipitate rhinitis and asthma attacks.
      Aspirin-induced asthma affects 5-10% of adult asthmatics, but remains largely
      underdiagnosed. The natural history of aspirin-induced asthma has been described,
      based on an extensive pan-European survey. All over Europe the disease develops
      according to a pattern in a similar, characteristic way, which might suggest a
      common underlying principle. Aspirin provocation tests with improved diagnostic
      accuracy have been developed, although no in-vitro test has been found to be of
      diagnostic value. At the biochemical level, aspirin-induced asthma is
      characterized by a chronic overproduction of cysteinyl leukotrienes. The key
      enzyme, LTC4 synthase, is overexpressed in bronchi and its mRNA is upregulated in
      peripheral blood eosinophils. The gene coding for LTC4 synthase exists in two
      common alleles, one of which appears to be associated with a severe, steroid
      dependent type of aspirin-induced asthma. Preliminary observations indicate that
      new, highly specific cyclooxygenase-2 inhibitors may soon become a safe
      alternative for aspirin-intolerant patients with asthma.

PMID- 11964667
TI  - Pollution and allergic airways disease.
AB  - The incidence of allergic diseases has increased dramatically over recent years
      in most industrialized countries of the world. Air pollution from motor vehicles
      has been implicated as one of the factors that are responsible for this increase.
      Epidemiological studies carried out in different geographical regions in the
      world have shown a significant and consistent association between ambient levels
      of pollutants and increased asthma and rhinitis symptoms. Recent human and animal
      exposure studies, as well as laboratory-based studies, have demonstrated that
      diesel particles, ozone and nitrogen dioxide induce an inflammatory response that
      involves various inflammatory cells, mediators and adhesion molecules, which
      could contribute to worsening of the allergic disorders. The present review
      describes our current understanding of the mechanisms by which pollutants such as
      diesel exhaust and ozone enhance the underlying allergic inflammatory response,
      and possibly explain the associations between pollutants and increasing allergic
      diseases noted in epidemiological studies.

PMID- 11964668
TI  - Allergen-specific immunotherapy in allergic rhinitis.
AB  - The scope of this review is to highlight important and interesting articles in
      the field of allergen-specific immunotherapy in allergic rhinitis published
      within the past year. The review is not intended to give a full overview of
      published literature but rather to focus on some subjects that I find significant
      in relation to the understanding of the specific treatment of allergies and to
      the selection of different treatment modalities. The most important aspects are
      how to define the most suitable candidates for the specific treatment, the
      mechanisms of action of immunotherapy and how to optimize treatment, and finally
      I include some reflections on the optimal presentation of the allergen to the
      immune system.

PMID- 11964669
TI  - Mechanisms of allergy and adult asthma.

PMID- 11964670
TI  - Allergen uptake and presentation by dendritic cells.
AB  - Allergic diseases such as atopic dermatitis, rhinitis and asthma are thought to
      result from a dysregulated immune response to commonly encountered antigens in
      genetically predisposed individuals. This response leads to chronic eosinophil
      rich allergic inflammation and is controlled by Th2 lymphocytes. The first step
      in the allergic immune response is the uptake and presentation of allergen by
      professional antigen presenting cells such as dendritic cells, macrophages and B
      lymphocytes. Immature dendritic cells reside in the epithelia of the skin, upper
      and lower airways and gut and have the potential to sense foreign antigens and
      non-specific inflammatory tissue damage. Following recognition and uptake of Ag,
      mature dendritic cells migrate to the T-cell rich area of draining lymph nodes,
      display an array of Ag-derived peptides on the surface of major
      histocompatibility complex molecules and acquire the cellular specialization to
      select and activate naive Ag-specific T cells. By the nature of the signals they
      provide to naive T cells, mature dendritic cells are critical for polarizing Th0
      helper cells into either Th1 or Th2 effector cells and for inducing long-lived
      memory Th cells. This article reviews recent information implying dendritic cells
      in the pathogenesis of allergic disease.

PMID- 11964671
TI  - Immunoglobulin E and its regulators.
AB  - Novel paradigms are emerging in the field of IgE regulation. Gene-environment
      interactions are increasingly considered to be major determinants of the type and
      amplitude of allergen-induced antibody responses. At the molecular level, the
      mechanistic connection between transcription and switching has been strengthened
      by the recent discovery that class switch recombination requires activation
      induced deaminase, a novel RNA editing enzyme. These findings will be critical
      for our understanding of the mechanisms that determine immunoglobulin isotype
      expression during immune responses.

PMID- 11964673
TI  - T-cell responses in allergy and asthma.
AB  - T-helper-2-type cytokines and some chemokines play an essential role in the
      pathogenesis of both allergy and asthma. A change in the T-helper 1/T-helper 2
      balance, caused by the dramatic change in the microbial environment of children,
      may account for the increasing prevalence of these conditions, but can also
      provide a conceptual basis for the development of new therapeutic strategies.

PMID- 11964672
TI  - The bronchial epithelium: translating gene and environment interactions in
      asthma.
AB  - The rising trends in asthma over the past 30 years are likely to be a consequence
      of changes in the environment acting on a susceptible genotype. Recognising that
      environmental agents impact on the bronchial epithelium, this structure is in a
      key position to translate and coordinate these gene-environment interactions. In
      asthma, the bronchial epithelium is stressed and damaged, with shedding of the
      columnar cells into the airway lumen. The aim of this review is to consider
      recent advances in our understanding of why the epithelium is damaged and how the
      ensuing repair responses orchestrate airway inflammation and remodelling leading
      to the development and maintenance of the asthmatic state.

PMID- 11964674
TI  - Immune effector functions of eosinophils in allergic airway inflammation.
AB  - Eosinophils have the capacity to exert immune effector actions on the airways of
      asthmatic individuals by virtue of their ability to elaborate cytokines,
      chemokines and growth factors. The present review discusses cutting edge research
      on eosinophil cytokine release and its potential role in allergic airway
      inflammation.

PMID- 11964675
TI  - Airway remodelling in the pathogenesis of asthma.
AB  - The inflammatory and remodelling processes that underlie asthma result from a
      highly complex interaction between various cell types. Apart from inflammatory
      cells, such as eosinophils, activated T cells, mast cells and macrophages,
      structural tissue cells such as epithelial cells, fibroblasts and smooth muscle
      cells can also play an important effector role through the release of a variety
      of mediators, cytokines and chemokines. This results in an acute inflammatory
      response that is characterized by vascular leakage, mucus hypersecretion,
      epithelial shedding and widespread airway narrowing. At the same time, through
      the release of mediators, cytokines, chemokines and growth factors, epithelial
      and mesenchymal cells cause persistence of the inflammatory infiltrate and induce
      structural changes in the airway wall, such as increased thickness of the
      basement membrane, increased collagen deposition, changes in bronchial
      microcirculation, and smooth muscle hypertrophy and hyperplasia. The end result
      of airway inflammation and remodelling is an increased thickness of the airway
      wall, leading to a reduced baseline airway calibre and exaggerated airway
      narrowing.

PMID- 11964676
TI  - Endogenous function and biological significance of aeroallergens: an update.
AB  - Significant advances have been made in delineating the structure and function of
      the clinically important aeroallergens. Most have now been characterized at the
      molecular level, and their endogenous function determined. In the period of
      review, however, several novel allergens have been identified. They include the
      house dust mite lipophorins and gelsolins, and the birch isoflavone reductase. In
      addition, the functions of previously described allergens have now been
      established or inferred on the basis of homology studies. For example, cat Fel d
      1 and the grass pollen group 1 allergens possess proteolytic activity and the
      thaumatin-like plant and pollen allergens possess endo-beta1,3-glucanase
      activity. Similarly, the lipocalin allergens may possess endonuclease activity,
      and the mite group 2 allergens may bind cholesterol. The three-dimensional
      structure of the horse dander lipocalin Equ c 1 and the honey bee Api m 2
      allergens have also been determined during the review period. Finally, in this
      period, a variety of novel or improved immunotherapeutic allergen reagents
      designed to redirect the host immune response from a T-helper-2 to a T-helper-1
      cell phenotype have been described, in particular, allergen and immunostimulatory
      CpG motif conjugates.

PMID- 11964677
TI  - Anti-immunoglobulin E for the treatment of allergic disease.
AB  - IgE plays a central role in allergic disease and participates in the associated
      inflammatory process. A mainstay of treatment of allergic disease, including
      asthma, is allergen avoidance and treatment of symptoms. Presently, the most
      effective treatments for allergic diseases are directed towards a regulation of
      the inflammatory process with corticosteroids. An exciting new approach is anti
      IgE (rhuMAb-E25), which would regulate the allergic process at the level of IgE.
      The following information will review recent experiences with anti-IgE and
      discuss the conditions in which this approach may be effective.

PMID- 11964678
TI  - Pediatric asthma and development of atopy.

PMID- 11964679
TI  - Growth and development of the lung.
AB  - Over the last half of the last century, classic studies established many features
      of the development of the lung in humans. Early studies relied on meticulous
      measurement and evaluation of lung morphology and physiology. In recent years,
      such studies have been supplemented by carefully conducted, longitudinal studies
      and by the use of molecular biological methodologies to determine more detailed
      aspects of lung development. In addition, factors affecting the growth of the
      lung have been evaluated including preterm delivery, antenatal steroids,
      environmental factors, asthma and asthma medications. In the future, further
      advances are likely to come from the molecular biological approach.

PMID- 11964681
TI  - Effects of maternal and early tobacco exposure on the development of asthma and
      airway hyperreactivity.
AB  - In 1999 a comprehensive review was published in Thorax that evaluated the role of
      exposure to tobacco smoke products (TSPs) in respiratory disease. The present
      review addresses papers published within the past 12 months on the effects of
      TSPs on childhood asthma and atopic disease, along with a few reports on possible
      mechanisms by which TSPs exert their adverse effects. Most of the observational
      studies published during the past year support the conclusion that both in-utero
      and, to some degree, passive (environmental) tobacco smoke (ETS) exposure
      adversely affect pulmonary function, and predispose to asthma symptoms and
      possibly bronchial hyperresponsiveness in childhood, but play little or no role
      in atopy development. However, in TSP-induced pulmonary disease, a mechanism of
      upregulation of pulmonary neuroendocrine cells has been hypothesized. An
      interventional study clearly demonstrated a need for a total (instead of partial)
      ban on indoor smoking in the homes of children with asthma in order to achieve
      significant reductions in levels of urinary cotinine. Because there is a large
      body of evidence for adverse effects of in-utero TSP as well as ETS exposure on
      respiratory health in children, we are in dire need of studies to elucidate when
      TSP exposure causes most damage, the mechanisms that underlie this damage, and
      how we can prevent unnecessary harm to the respiratory system in the vulnerable
      child.

PMID- 11964680
TI  - Exposure and sensitization in infants and children.
AB  - The complex relationship between allergen exposure, atopic sensitization and
      asthma in individuals and in populations has recently been a subject of
      controversy. A number of studies have demonstrated that allergen exposure in
      sensitized asthmatic individuals increases the severity of disease. A simple dose
      response relationship between mite allergen exposure and specific sensitization
      in infants and children has been confirmed. However, the concept that there is a
      direct relationship between allergen exposure and the initiation of asthma has
      been challenged. The relationship between allergen exposure and subsequent
      disease development is complex, and is confounded by a number of important
      factors. Populations and individuals are exposed to a mixture of several
      allergens, irritants and pollutants, and we know very little about the impact of
      these mixtures and their possible synergistic effect. The dose-response
      relationship between allergen exposure and allergic disease may not be linear,
      and may be different for different allergens. For example, a protective effect of
      cat ownership on sensitization and allergic disease has been reported, raising
      the question of whether the dose-response relationship between exposure and
      sensitization may be different for cat compared with mite allergen. It has been
      suggested that many children who are exposed to a high level of cat allergen make
      a modified T helper type 2 response, characterized by the presence of IgG4
      antibody to cat proteins without becoming allergic (i.e. no IgE response), which
      could be regarded as a form of tolerance. This could explain a decreased risk of
      asthma in children living in homes with cats, without invoking a concept of a
      shift in the balance of T helper types 1 and 2 responses. Cat allergen is
      ubiquitous, and passive exposure (e.g. home without cats and public places) may
      induce specific IgE responses in non-cat owners, whereas those exposed to very
      high levels of cat allergen may initially mount an IgE response, which may be
      replaced by a modified T helper type 2 response (tolerance). It is likely that
      the population susceptibility to allergic sensitization and also end-organ
      responsiveness has altered, and allergen exposure may still be important in
      initiating disease in an increasingly susceptible population, although the
      pattern may differ for different allergens.

PMID- 11964682
TI  - Role of food allergy in asthma in childhood.
AB  - Atopy is the major predisposing factor for asthma identified up to now, and
      allergen exposure, particularly indoor allergens, is considered as a causal
      factor for asthma. Food allergy is frequently underestimated in association with
      asthma, however food allergy has been shown to trigger or exacerbate broncho
      obstruction in 2 to 8.5% of children with asthma. There is also evidence that
      double-blind placebo-controlled oral challenge is able to increase unspecific
      bronchial hyperresponsiveness. Sensitization to food can occur early in life
      involving T cell response, mainly of the Th2 phenotype, but also IgE-mediated
      hypersensitivity. Moreover, it has been shown that sensitization to food
      allergens early in life is a risk factor for sensitization to inhalent allergens
      and respiratory symptoms later on. Epidemiological studies suggest that changes
      in the dietary composition, such as trans-fatty acids, could be involved in the
      increase of asthma prevalence. The introduction of formula during the first
      trimester of life increases the risk of having asthma. The diagnosis of food
      allergy associated with asthma is not easy, nevertheless is important for
      allergists, pulmonologists and paediatricians to consider food allergy in
      children with respiratory symptoms, especially when asthma symptoms start early
      in life and when they are associated with other manifestations of food allergy.
      Children sensitized to cow's milk proteins and also having atopic eczema are at
      higher risk for asthma. Since avoidance of the offending food is the first step
      in the management of children with asthma associated with food allergy, a careful
      identification should be done in order to avoid unnecessary elimination of foods.

PMID- 11964683
TI  - The role of farm exposures in occupational asthma and allergy.
AB  - Agriculture is very diverse. Farmers commonly grow several different crops, and
      may also raise animals. They are exposed to a variety of antigens from plants,
      animals, insects and molds, to which they may become allergic. However, several
      large epidemiological studies conducted recently in various regions of the world
      indicate that the prevalence of asthma and allergy is no higher in farmers than
      in other populations. There is increasing evidence that growing up on a farm may
      protect against developing asthma and allergic rhinoconjunctivitis.

PMID- 11964684
TI  - Role of human leukocyte antigen phenotype and exposure in development of
      occupational asthma.
AB  - Studies of factory workforces in the past decade, exposed to both inhaled protein
      allergens (e.g. enzymes) and low molecular weight sensitisers (e.g. acid
      anhydrides), have provided consistent evidence of exposure-response relationships
      for both sensitisation (IgE production) and asthma. The development of molecular
      techniques has allowed investigation of candidate gene, in particular HLA Class 2
      alleles, as risk factors contributing to individual susceptibility, in particular
      to low molecular weight chemicals. The frequency of HLA DR3 in cases of
      sensitisation to trimellitic anhydride and ammonium hexachloroplatinate is
      increased as compared to referents who have experienced a comparable intensity
      and duration of exposure. Similarly, HLA DQB1Asp57 is consistently more frequent
      in cases of isocyanate induced asthma. These observations indicate HLA Class 2
      molecules contribute to individual susceptibility to sensitisation and asthma
      caused by low molecular weight chemicals. A study of platinum refinery workers
      suggested the relative risk associated with HLA phenotype was greater at lower
      levels of exposure.

PMID- 11964685
TI  - Workplace irritant exposures: do they produce true occupational asthma?
AB  - The recognition that irritant exposures can cause asthma is not new. Many
      investigators turn towards the gassings of soldiers in World War I as the first
      examples of this, while Brooks, in 1985, reported this in detail in workers and
      called it 'Reactive Airways Dysfunction Syndrome (RADS)'. There is considerable
      overlap with RADS and occupational asthma as both share respiratory symptoms
      which can be described as 'asthmatic', yet RADS is the result of an acute
      excessive exposure, while occupational asthma occurs due to a series of
      sensitizing exposures. Yet, a clear understanding of RADS has been limited by the
      lack of epidemiologic studies; rather the disease has been described by case
      series. This report contrasts RADS and occupational asthma and finds that
      although there may be some difference in lung pathology, reports for the past
      years since Brooks' initial reports have shown that the line separating
      occupational asthma and RADS has become increasingly blurred, rather than
      increasingly distinct, with considerable overlap in the clinical symptoms with
      the perspective that these described entities are a part of a continuum. Perhaps
      the development of animal models for RADS may hasten further understanding.

PMID- 11964686
TI  - Recent developments in diisocyanate asthma.
AB  - Despite recent advances in our understanding of diisocyanate-induced asthma, this
      disease remains a perplexing phenomenon. Studies reported in the past year have
      focused on: (i) diisocyanate antigens; (ii) the role of airway and skin
      epithelium; (iii) human immune responses to exposure; (iv) neurogenic pathways;
      and (v) genetic factors that may confer susceptibility. These studies support the
      hypothesis that diisocyanate asthma results from the host immune response to
      these chemicals, and may represent a mixed T helper type 1/2 response. A better
      understanding of the pathogenesis of diisocyanate asthma should facilitate the
      development of better diagnostic tests and strategies for disease surveillance
      and intervention.

PMID- 11964687
TI  - The role of plant panallergens in sensitization to natural rubber latex.
AB  - Latex allergy represents an increasing occupational problem, mainly among
      healthcare workers. An association between latex allergy and hypersensitivity to
      some plant foods, particularly fruits (the latex-fruit syndrome), has been
      established. Class I chitinases with an N-terminal hevein-like domain from
      avocado, chestnut, banana and other foods, and latex hevein seem to be the
      allergens responsible for the cross-reactions involved in the latex-fruit
      syndrome. The potential role of other latex allergens, such as profilin, Hev b 5,
      Hev b 7 and beta-1,3-glucanases, in the co-sensitization to latex and plant foods
      is also discussed.

PMID- 11964688
TI  - Are we closer to developing threshold limit values for allergens in the
      workplace?
AB  - The use of immunoassays has facilitated the measurement of high molecular weight
      sensitizers, usually protein molecules, in the picogram and nanogram per cubic
      meter range. This facilitated the evaluation of exposure response relationships
      for bakery workers, exposed to wheat allergens and fungal alpha-amylase and other
      groups exposed to other allergens such as laboratory animal workers. The
      application for the standard setting is still limited and requires rigorous
      standardization, but can be expected in the near future.

PMID- 11964689
TI  - Asthma outcome measures.

PMID- 11964690
TI  - New insights from lung function.
AB  - Asthma is a disease that is, in large part, defined by abnormalities of pulmonary
      function. Failure of any new treatment modality to improve objective measures of
      lung function suggests a limited usefulness of such new therapies. The clear
      dissociation between inflammation and airways responsiveness indicates the latter
      is not solely dependent on the former. Recent long-term treatment trials suggest
      that monitoring the degree of airways responsiveness, and returning
      responsiveness toward a normal value should be an obtainable goal of therapy. The
      effects of large inhalations and loss of lung volume dependence suggest that
      linkage between the airways and lung parenchyma are a key to maintenance of
      airway patency. Measurement of lung function remains the most practical means for
      the assessment of permanent changes in lung structure. New developments in
      monitoring lung function, especially using forced oscillation approaches, show
      particular promise in assessing the lung function of the asthmatic person.

PMID- 11964691
TI  - Measuring asthma control.
AB  - Asthma control may be defined in several ways, but in clinical practice refers to
      the achievement of an acceptable clinical state, often based on goals of asthma
      management. It differs from the assessment of disease severity, which quantifies
      departure from 'normal'. Most references to asthma control in the current
      literature refer to one or more endpoints rather than a comprehensive composite
      assessment based on relevant clinical features of the disease. Recent
      developments have been the introduction of validated measurement tools such as
      the Asthma Control Questionnaire and Asthma Control Diary, which include
      symptoms, beta-agonist use and a measure of airway calibre, each scored on a 7
      point scale and then aggregated. An alternative view is that a wholly patient
      focused outcome (based entirely on patient recall of symptoms over the last week
      or month) is preferable. In general, however, care-givers appear to favour the
      inclusion of objective measures, and a range of indicators of disease activity
      are being investigated, including airway hyperresponsiveness and markers of
      airway inflammation. The potential value of the wider use of a composite measure
      of clinical control is being increasingly recognized, and further attempts to
      develop, validate and apply a simple tool suitable for use in primary care are
      underway.

PMID- 11964692
TI  - Exhaled markers of inflammation.
AB  - Exhaled markers of inflammation allow completely noninvasive monitoring of
      inflammation and oxidative stress in the respiratory tract in inflammatory lung
      diseases, including asthma, chronic obstructive pulmonary disease, cystic
      fibrosis, bronchiectasis and interstitial lung diseases. Such noninvasive
      techniques are simple to perform, may be repeated frequently and can be applied
      in children, including neonates and patients with severe disease in whom more
      invasive procedures are not possible. Several volatile chemicals can be measured
      in the breath (nitric oxide, carbon monoxide, hydrocarbons), and many nonvolatile
      molecules (mediators, oxidation and nitration products, proteins) may be measured
      in exhaled breath condensate.

PMID- 11964693
TI  - The epidemiology of food allergy.
AB  - In contrast to respiratory allergies, the epidemiology of food allergy has been
      little studied, and there is no strong evidence for an increasing incidence,
      either among infants and children or in adults. Neither are there any studies
      showing regional differences in prevalence. On the contrary, studies in Estonia,
      Iceland and Sweden indicate a similar prevalence during the first 2 years of
      life, both in verified food allergy and reported food intolerance. This is
      despite a low prevalence of respiratory allergies in the two former countries and
      a high prevalence in Sweden. The major problem with such epidemiological studies
      lies in the fact that there are no simple diagnostic criteria to verify the
      diagnosis. So far IgE determinations have been the only available diagnostic
      test, and their value is limited by poor sensitivity and the fact that at best
      they would only verify a small proportion of food intolerance, i.e. that caused
      by IgE-mediated reactions. A diagnosis of food allergy/intolerance must be based
      on a double-blind placebo-controlled food challenge, and not on the patient's or
      doctor's impression. More studies are required from different regions in order to
      identify similarities and differences in the patterns of food allergy. In
      particular, there is a need for properly conducted epidemiological studies in
      adults. Such studies should be interdisciplinary, as the cultural and social
      perceptions of food allergy and food intolerance would be expected to have a
      major impact on prevalence, perhaps even more than medical factors.

PMID- 11964694
TI  - Prevention.
AB  - The development of food allergy depends on several factors, including genetic
      factors and early exposure to allergenic proteins in the diet, food protein
      uptake and handling, and the development of tolerance. Many hypotheses, as
      regards the possible causal relationships, have been raised during the past few
      years, including the hygiene theory, the role of bacterial gut flora, and the
      potential effect of different cytokines in breast milk. Although interesting,
      these are mainly speculations based on non-interventional and often
      retrospective/cross-sectional studies including small study populations. These
      theories remain to be documented in proper, controlled and prospective studies.
      Breastfeeding and the late introduction of solid foods (>4 months) is associated
      with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing
      and asthma in early childhood. In all infants, breastfeeding should be encouraged
      for 4-6 months. In high-risk infants a documented extensively hydrolysed formula
      is recommended if exclusive breastfeeding is not possible for the first 4 months
      of life. There is no evidence for preventive dietary intervention neither during
      pregnancy nor lactation. Preventive dietary restrictions after the age of 4-6
      months are not scientifically documented.

PMID- 11964695
TI  - Sensitization and tolerance.
AB  - The mechanisms responsible for sensitization, in particular within the
      gastrointestinal tract, are IgE-mediated as well as of a non-IgE-mediated,
      immunological origin. The phenomenon that is the opposite of sensitization is the
      maintenance of tolerance and is exemplified by the phenomenon 'oral tolerance'.
      The cytokines transforming growth factor beta and interferon gamma have been
      shown to be key immunoregulatory cytokines in oral tolerance. A new experimental
      model of eosinophilic allergic gastroenteritis has been developed with the use of
      encapsulated dietary antigen. The model was used in mice with genetic deletions
      of the eosinophil chemokine eotaxin or of the cytokine IL-5, demonstrating the
      importance of eotaxin. In clinical allergy research, a major question has been to
      explain the global increase in asthma and allergy. The 'hygiene hypothesis'
      states that a lack of maturation of the infant immune system from a T helper 2 to
      a T helper 1 type of immune response may be caused by less microbial stimulation
      in Western societies. Several lines of data support this hypothesis. However,
      apart from the genetic constitution of the individual, breastfeeding in infancy
      may be the most important single determinant for the development of clinical
      tolerance.

PMID- 11964696
TI  - Food allergens.
AB  - A number of advances in the scientific knowledge concerning adverse food
      reactions have been made in the past few years. Understanding about the nature of
      the food allergen itself, the molecular characterization of the epitopes on these
      allergens, the pathophysiology of the clinical reaction, and the diagnostic
      methods have all been significantly enhanced.

PMID- 11964697
TI  - In-vitro diagnosis: serum-based methods used for risk assessment of allergenic
      food.
AB  - This review on in-vitro diagnostic methods focuses on the use of methods to
      perform risk assessment on foods. Based on the International Life Science
      Institute (ILSI) risk decision tree, the methods are discussed and three
      scenarios are suggested: (i) testing for a well-known allergen; (ii) testing for
      a well-known allergen, but with no previous history of food allergy; and (iii)
      testing for unknown allergens and cross-reactivity with known allergens.

PMID- 11964698
TI  - Food allergy: in-vivo diagnostics including challenge.
AB  - The diagnosis of food allergy related to IgE-mediated reactions is based on the
      establishment of the allergic origin of the symptoms and the identification of
      the causal allergen or allergens. The double-blind, placebo-controlled food
      challenge remains the 'gold standard' for the in-vivo diagnosis of specific food
      allergy. Valuable information can be obtained with both in-vitro and in-vivo
      diagnostic procedures; however, for the accurate prediction and diagnosis of food
      allergy, these methods must be standardized and correlated with a standardized
      double-blind, placebo-controlled food challenge procedure.

PMID- 11964699
TI  - Atopic allergens of plant foods.
AB  - The exact knowledge of what structural characteristics of an antigen are
      responsible for its allergenicity may not be available for several years.
      However, it is striking that the majority of the plant food allergens are
      clustered within a few protein families, and these are reviewed in this article.
      In most cases, plant food allergens are proteins that ensure the survival of the
      species as either seed storage proteins or proteins that are actively involved in
      the defence of the organism.

PMID- 11964700
TI  - Hidden food allergens.
AB  - This review summarizes recent advances and findings in the area of 'hidden' food
      allergens, i.e. allergenic foods that can either contaminate other foods, or be
      'disguised' as part of a food, and cause allergic reactions. Newly emerging
      allergenic foods of increasing importance, recently developed methods for the
      detection of allergenic residues, the potential allergenicity of genetically
      engineered foods, and some unexpected sources of food allergens are described.

PMID- 11964701
TI  - Drug allergy.

PMID- 11964702
TI  - Drug metabolism in the skin.
AB  - The skin performs a wide range of active metabolic functions including xenobiotic
      metabolism involving metabolizing enzymes specific to the skin. In this review we
      focus on the role of drug metabolism: (i) in allergic reactions to substances of
      low molecular weight; (ii) in cutaneous vitamin A and D3 metabolism and its
      modulation; (iii) in the interaction of transport and metabolic enzymes in skin
      cells; and (iv) on novel tools for the measurement of drug metabolism in various
      compartments of the human skin.

PMID- 11964703
TI  - Physiopathology and treatment of severe drug eruptions.
AB  - This review will focus on recent advances concerning the most severe cutaneous
      drug reactions: the Stevens-Johnson syndrome, toxic epidermal necrolysis, and
      drug reactions with eosinophilia and systemic symptoms. The most significant
      progress concerned the demonstration that drugs more often than reactive
      metabolites are immunogenic and induced several kinds of responses. These
      findings provided the rationale for using new therapeutic approaches, which will
      be discussed.

PMID- 11964704
TI  - Immunohistology of drug-induced exanthema: clues to pathogenesis.
AB  - Hypersensitivity reactions to drugs can cause a variety of different skin
      disorders, the most frequent being maculopapular eruptions. In recent years
      increasing evidence has indicated the important involvement of T cells in this
      drug reaction. Histopathological changes typically show a dominant T-cell
      infiltration together with vacuolar interface dermatitis. Immunohistochemical
      studies demonstrate the presence of cytotoxic CD4+ and CD8+ T cells, which
      contain perforin and granzyme B, in close proximity to keratinocytes showing
      signs of cell destruction. Expression of Fas ligand is barely detectable, which
      suggests that cytotoxic granule exocytosis may be the dominant pathway leading to
      keratinocyte cell damage. In addition, drug-specific T cells may orchestrate the
      inflammatory skin reaction through the release and induction of various cytokines
      (i.e. IL-5, IL-6, TNF-alpha, IFN-gamma) and chemokines (i.e. regulated on
      activation, normal T-cell expressed and secreted; eotaxin). These mediators
      contribute to the generation of eosinophilia, which may amplify the underlying
      immune response through the release of further proinflammatory mediators in drug
      induced maculopapular exanthema.

PMID- 11964705
TI  - Epidemiology of drug allergy.
AB  - Adverse drug reactions occur in 10-20% of hospitalized patients, and up to one
      third of these are of an allergic or pseudo-allergic nature. Allergic reactions
      are unpredictable adverse effects that are linked to immunological mechanisms.
      Pseudo-allergic reactions are unpredictable adverse reactions that are clinically
      similar to allergic reactions, but for which there are no drug-specific
      antibodies or T lymphocytes. There is a paucity of tools that allow a definite
      diagnosis, and most of the available ones still require validation. Therefore,
      there are few true epidemiological data, and most of those that are available,
      including incidence, mortality and socioeconomic impact data, should be
      interpreted with caution.

PMID- 11964706
TI  - HIV and drug allergy.
AB  - Drug-related rashes have been estimated to be 100 times more common in HIV
      positive patients than in the general population. The reasons for this are not
      clear, but are likely to be multifactorial, and include changes in drug
      metabolism, oxidative stress, cytokine profiles and immune hyperactivation. HIV
      itself may also serve as a danger signal, leading to the development of an immune
      response rather than tolerance. Drugs that are implicated in causing
      hypersensitivity have changed since the advent of highly active antiretroviral
      therapy. This is largely as a result of a decrease in the use of antimicrobials
      such as co-trimoxazole, and the introduction of new drugs of different classes,
      including abacavir, non-nucleoside reverse transcriptase inhibitors such as
      nevirapine, and protease inhibitors such as amprenavir. Laboratory evidence
      supporting a role of the immune system in the mechanism of co-trimoxazole
      hypersensitivity is available. However, this is not the case for the newer
      antiretrovirals; hypersensitivity to these agents is presumed to be immune
      mediated based only on the symptomatology. It is essential that research be
      carried out into the mechanisms of hypersensitivity reactions associated with
      these important new classes of drugs so that their benefit-risk ratio can be
      improved, and lessons learned for future drug development.

PMID- 11964707
TI  - Reactive metabolites and their role in drug reactions.
AB  - Adverse drug reactions are a major clinical problem and often preclude drug
      administration. Drug hypersensitivity (or allergy) represents one of the most
      severe and unpredictable reactions associated with drug therapy. Our current
      understanding of drug hypersensitivity is based on the hapten hypothesis of
      immune recognition of drugs by T cells. The onset of hypersensitivity involves
      drug bioactivation, covalent binding, followed by uptake, antigen processing and
      T cell proliferation. There is convincing evidence that drugs associated with a
      high incidence of hypersensitivity are converted to protein reactive
      intermediates by the normal processes of drug metabolism and stimulate a cellular
      immune response in sensitive individuals. Until recently, however, there has been
      little evidence to relate the formation of a reactive metabolite to the
      initiation of a cellular immune response. The purpose of this review is to detail
      recent advances in our understanding of the complex mechanisms of drug
      hypersensitivity, and using severe skin reactions as an example, assess recent
      evidence that supports the hapten hypothesis of drug hypersensitivity.

PMID- 11964708
TI  - Chemistry of drug allergenicity.
AB  - Of the very large number and variety of drugs used in medicine, those that are
      frequently implicated in immediate allergic reactions are relatively small in
      number and include neuromuscular blocking drugs used in anaesthesia, beta-lactam
      antibiotics, some other antibacterial agents including broad-spectrum antibiotics
      and quinolones and, less often, some narcotics. Structure-activity and
      immunochemical investigations have been most numerous and detailed for
      neuromuscular blocking drugs and beta-lactams, particularly penicillins. For the
      former group of drugs, morphine is proving to be a useful agent for the in-vitro
      detection of clinically relevant neuromuscular blocking drug-- as well as
      morphine- and fentanyl-reactive IgE antibodies. The employment of so-called
      'major' and 'minor' determinants for a range of different penicillins and
      cephalosporins has revealed previously unsuspected heterogeneity in patient
      recognition responses, and has reinforced findings on the allergenic importance
      of side-chain groups. Many reports have been published on anaphylaxis to
      chlorhexidine, and progress in identifying allergenic determinants is reviewed
      together with the still inadequately understood subject of IgE antibody
      recognition of quinolone antibacterial agents.

PMID- 11964709
TI  - Recent advances in the diagnosis of drug allergy.
AB  - The diagnosis of immunologic drug reactions is based primarily on a detailed
      clinical history and historical data on relative immunogenicity of the culprit
      drugs. Except for a few standardized skin tests, most of the other methods for
      diagnosing drug allergy have unproven diagnostic or predictive clinical utility.
      Many tests for drug-specific immune responses are suggestive if positive, but
      have unknown negative predictive values. The present review addresses the most
      recent published literature regarding the diagnosis of drug allergy. Recent
      advances in the use of the lymphocyte transformation test, and delayed
      intradermal skin tests and patch tests for the diagnosis of delayed cutaneous
      reactions to penicillins suggest that these tests may have clinical utility,
      although confirmatory reports are still missing. For the diagnosis of acute
      vaccine reactions, gelatin-specific IgE as measured by radioallergosorbent test
      has now been shown to be reliably associated with allergic reactions to gelatin
      containing vaccines.

PMID- 11964710
TI  - Stinging ants.
AB  - Ants belong to the order Hymenoptera, along with bees, wasps, yellow jackets,
      etc., they are the most successful animal genera in this world. It is their
      selfless social structure which accounts for their huge impact. Their effect on
      man ranges from the parasol ant, which makes plant cultivation untenable in
      certain parts of South America, to Solenopsis Invicta in the southeastern United
      States of America, which kill ground dwelling birds and small animals, harass
      livestock, and renders farmland unusable. With the exception of the Bulldog Ant
      of Australia (which is the size of a medium cockroach) direct toxic effects are
      not a lethal threat to man. Human fatalities and morbidity are related to
      secondary infections of excoriated stings or allergic anaphylaxis. This article
      reviews history and recent developments regarding stinging ants around the world.

PMID- 11964711
TI  - Mosquito bite pathogenesis in necrotic skin reactors.
AB  - Mosquito bite exposure results in a variety of reactions and secondary
      complications. Clinical hypersensitivity manifests primarily as local reactions
      with anaphylaxis being a very rare event. Risk factors for more severe local
      reactions include immunodeficiency, young children and visitors to an area with
      new exposure to indigenous mosquitoes. Necrotic skin reactions to mosquito bites
      have been associated with a newly recognized hemophagocytic syndrome in
      predominantly oriental populations. Diagnostic and therapeutic agents in the
      clinical management of mosquito hypersensitivity remain limited, but recent
      discovery of 3 recombinant proteins (rAed a 1, rAed a 2, rAed a 3) shared by
      several mosquito species promise to be more specific skin test antigens for the
      future.

PMID- 11964712
TI  - Discontinuing venom immunotherapy.
AB  - The decision to discontinue venom immunotherapy requires a great deal of clinical
      judgement because of the potential for a life-threatening reaction to a sting.
      The risk of recurrence is a combination of the frequency of reaction and the
      severity of reaction. Early studies reported a relapse rate of 8-14% in
      radioallergosorbent test-negative patients when therapy was stopped after 3
      years. Unfortunately, the venom skin test or radioallergosorbent test becomes
      negative in only 25% of patients after 5 years of treatment. An alternative
      criterion for stopping treatment after 5 years regardless of the skin test has
      been equally successful, with most post-treatment reactions being much milder
      than pre-treatment reactions. There was no evidence of a rebound of venom
      sensitivity when therapy was stopped, even when patients were stung. The level of
      venom-specific IgE antibodies is better suppressed by 5 than by 3 years of
      treatment. The risk of relapse is higher in honeybee-allergic patients and in
      patients who had a systemic reaction (to a sting or an injection) during therapy.
      The frequency of reaction may be low, but patients who had very severe pre
      treatment reactions have a greater chance of the reaction being severe again, and
      should remain on therapy for life. Long-term observations show that the incidence
      of systemic reaction to a sting remains 10% for each sting that occurs, even 10
      15 years after stopping treatment. Because patients may not react to one sting
      and then subsequently react to another sting, the cumulative frequency of sting
      reactions is approximately 17% after 10 years off treatment. Moreover, negative
      venom skin tests are not a guarantee of safety because there is almost the same
      10% frequency of reaction in patients who appear to lose sensitivity. It is not
      yet clear whether some low-risk patients (children, mild reactors) could
      discontinue treatment after just 3 years.

PMID- 11964713
TI  - Anaphylaxis: issues in diagnosis.
AB  - Although anaphylaxis continues to be recognized as a life-threatening clinical
      problem, efforts to develop in-vitro methods for diagnosis and verification
      continue. The results have been interesting but not yet definitive, so that the
      necessity for clinical diagnosis remains pivotal.

PMID- 11964714
TI  - Allergy to bumblebee venom.
AB  - Allergy to bumblebee venom is a rare form of Hymenoptera venom allergy. Because
      bumblebees are increasingly used for the pollination of greenhouse plants, the
      prevalence of this Hymenoptera allergy has increased during the past decade. The
      clinical presentation, diagnosis and therapy of bumblebee venom allergy are
      similar to other Hymenoptera venom allergies. There is a significant
      immunological cross-reactivity between bumblebee and honeybee venom. It has been
      claimed that immunotherapy with honeybee venom can protect patients with
      bumblebee venom allergy. This concept, however, has been called into question
      after the finding of bumblebee venom-specific IgE lacking cross-reactivity to
      honeybee venom, and three cases of bumblebee venom-allergic patients in whom
      immunotherapy with honeybee venom was unsuccessful. Immunotherapy with pure
      bumblebee venom has been shown to be effective and safe, and is currently the
      treatment of choice in individuals who cannot avoid contact with bumblebees.
      Immunotherapy with honeybee venom, however, should be considered in patients with
      severe reactions to bumblebee stings and concurrent sensitization to honeybee
      venom.

PMID- 11964715
TI  - New insight into immunological mechanisms of venom immunotherapy.
AB  - The early production of IL-10 appears to induce T cell anergy and is an important
      step in venom immunotherapy. This results in the loss of the abnormal venom
      specific T helper type 2 response (reduced proliferation and cytokine production)
      and a switch from a T helper type 2 dominant to a T helper type 1 dominant
      cytokine response. As a consequence, there is an increase in specific IgG4, an
      increase in the specific IgG4:IgE ratio, and over the longer term a decrease in
      specific IgE. IL-10 is initially produced by allergen-specific T cells, but later
      by B cells and monocytes. IL-10 initiates anergy in T cells by blocking tyrosine
      phosphorylation of CD28 and inhibiting the CD28 co-stimulatory signal. IL-10 also
      inhibits cytokine gene transcription and messenger RNA production. That clinical
      protection in venom immunotherapy occurs earlier than antibody changes suggests
      that additional mechanisms may be operative. Decreased basophil mediator release
      is a candidate and has been demonstrated: it is induced by IL-10 and possibly
      also related to changes in chemokines and other cytokines. Proliferation and
      cytokine secretion in anergic T cells can be restored depending on the cytokine
      milieu. Restimulation in the presence of IL-2, IL-15 and possibly IL-12 leads to
      a T helper type 1 cytokine pattern (immunity:effective immunotherapy) and with IL
      4 a T helper type 2 pattern (persistence of allergy:relapse). The cytokine
      microenvironment in tissues can thus influence outcome. A variety of new
      approaches to immunotherapy is being investigated, including peptide therapy.
      Preliminary data from DNA vaccines, largely in animal models, hold great promise.
      Immunostimulatory DNA sequences have an adjuvant effect and induce T helper type
      1 cytokines, independent of antigen. They may be co-administered with allergen
      and used to redirect allergen-specific T helper type 2 responses.

PMID- 11964716
TI  - Genetics and epidemiology.

PMID- 11964717
TI  - Genes for atopy and asthma.
AB  - The genetic basis of atopic diseases is represented by a complex network of
      interacting genes or common genetic variants rather than a few disease-causing
      mutations. The individual risk of developing asthma or other atopic diseases is
      defined by the concert of interaction of these hereditary factors and
      environmental stimuli. The first decade of asthma genetics has been spent
      identifying those genetic regions through linkage analysis, which are likely to
      harbour asthma genes. At the same time, several candidate genes for asthma and
      atopy have been identified and their variants characterized, some of them even to
      a level of functional understanding. Rather than adding new candidate regions and
      genes to the pool of knowledge, the interest in the past year has moved to a more
      sophisticated statistical evaluation of the given linkage and association data
      and a more precise definition of so-called 'intermediate phenotypes'. Some of the
      results are quite surprising and have helped us to understand the underlying
      pathophysiology. For example, the distinct clinical traits of asthma, such as
      atopic sensitization or inflammation of the bronchial epithelium, seem to be
      defined by distinct subsets of predisposing genes. At the same time, the very
      same subsets of genes might underlie further clinical diseases with similar
      clinical features. Polymorphisms within IL-4R alpha, which had been shown to be
      associated with asthma and atopy, have also been shown to be associated with
      kidney allograft rejection, systemic lupus erythematosus and Crohn's disease.
      There might thus just be a few asthma and atopy genes. Finally, asthma and atopy
      genetics has now reached a point of practical application. The genetics of
      susceptibility to environmental stimuli, pharmacogenetic data, and the advent of
      new pharmaceutical targets will greatly influence the whole field of asthma and
      atopy.

PMID- 11964718
TI  - Linkages and associations to intermediate phenotypes underlying asthma and
      allergic disease.
AB  - Considerable effort and expense has been expended in attempts to detect specific
      polymorphisms in genetic loci contributing to susceptibility to allergic
      diseases. Increasingly, 'intermediate' phenotypes for asthma and other allergic
      diseases have become the focus of such investigations, due to disease
      heterogeneity and the difficulty of defining disease status. Together with meta
      analysis of existing linkage datasets and the completion of many second-stage and
      specialized genome scans, the recent focus in asthma and atopy genetics has been
      on single nucleotide polymorphism discovery and genotyping in candidate genes.

PMID- 11964719
TI  - The common genetic hypothesis of autoimmune/inflammatory disease.
AB  - Individual inflammatory and autoimmune diseases are discrete clinical entities.
      The clinical presentation of any specific inflammatory disease is the culmination
      of complex interactions between genetics, primary and secondary immune effector
      mechanisms, and environmental triggers. Although often different in clinical
      presentation, common cellular and molecular immune pathways have been shown to be
      intimately involved in the destruction of different target tissues in different
      disease states, which ultimately defines specific diseases. At the genetic level,
      comparative genomic analysis of autoimmune and inflammatory disorders suggests
      shared genetic components for these clinically related diseases. This leads to a
      common genetic hypothesis which states that, unlike classical mendelian genetic
      disorders, common autoimmune and inflammatory disorders arise from combinatorial
      interactions of common non-disease specific loci, disease specific loci, and
      specific environmental triggers.

PMID- 11964720
TI  - The role of indoor allergen exposure in the development of sensitization and
      asthma.
AB  - The role of indoor allergen exposure in the development of sensitization and
      asthma remains a subject of controversy. From a number of cross-sectional and
      longitudinal studies we can conclude that there is a very close association
      between allergen exposure and the sensitization of an individual. The dose
      response relationships seem to differ between allergens; house dust mite and
      cockroach allergens appear to have a positive linear relationship, whereas cat
      allergens appear to act quite differently, with maximum sensitization developing
      at moderate exposure levels. Very low levels of cat allergen exposure are likely
      to induce no response and very high levels are likely to develop a form of
      tolerance, with a modified T helper cell type 2 response and the production of
      IgG4 antibodies and but not IgE. The relationship between indoor allergen
      exposure and asthma is, however, less clear. The proposed mechanism for the
      development of disease is that allergen exposure causes sensitization, and
      continued exposure leads to airway responsiveness and inflammation. As yet, the
      evidence for allergen exposure being a primary cause of asthma remains weak, and
      the results of ongoing prospective, randomized allergen avoidance trials are
      awaited to clarify this issue.

PMID- 11964721
TI  - Are infections protecting from atopy?
AB  - The 'Hygiene Hypothesis' proposes that overcrowding and unhygienic contacts early
      in life may protect from atopic diseases by facilitating exposure to microbes.
      Longitudinal studies have recently shown that among subjects exposed early in
      life to other children at home, or at day care, the risk of wheezing steadily
      declined with age to levels significantly lower than controls. Evidences
      supporting a protective role of respiratory infections or BCG immunization on the
      development of allergic asthma are still insufficient. By contrast, the
      observation of a lower prevalence of atopic sensitization among children raised
      on a farm has been consistently reproduced. Several new studies have recently
      investigated the role of changes of human microbial flora, declining exposure to
      foodborne and orofecal infections, to helminths and to environmental sources of
      endotoxin as putative contributors to the rise of allergy and asthma cases among
      populations living with a western lifestyle.

PMID- 11964722
TI  - Dietary antioxidants and adult asthma.
AB  - The triggers and causes of asthma have long been topics of investigation by
      epidemiologists. The current concept of asthma and atopy is that the onset of the
      disease and its clinical course are determined by gene environment interactions;
      that is, those individuals who develop asthma are both genetically susceptible
      and receive appropriate environmental stimuli. One potential environmental factor
      that may relate to disease etiology is diet. This article will review the
      published evidence for the effects of dietary antioxidants on asthma incidence
      and disease control.

PMID- 11964723
TI  - Applying statistical approaches in the dissection of genes versus environment for
      asthma and allergic disease.
AB  - Now that some of the genes involved in asthma and allergy have been identified,
      interest is turning to how genetic predisposition interacts with exposure to
      environmental risk factors. These questions are best answered by studies in which
      both genotypes and other risk factors are measured, but even simpler studies, in
      which family history is used as a proxy for genotype, have made suggestive
      findings. For example, early breast feeding may increase the risk of allergic
      disease in genetically susceptible children, and decrease the risk of 'sporadic'
      allergy. This review also addresses the overall importance of genetic causes of
      allergic disease in the general population.

PMID- 11964724
TI  - Neuroimmune interactions in the skin.
AB  - Neuroimmunologic aspects of skin inflammation involve several interacting
      systems. The modulating influence of autonomic and sensory nerves has been known
      for a long time. Neurokinines derived from these nerves have recently been shown
      to interact with antigen presentation in dermal Langerhans cells and other key
      functions of allergic skin disease. While some mechanisms of afferent function
      and local reflex are known, the nature of efferent effects (from brain to
      periphery) remains to be elucidated. New aspects include involvement of the brain
      derived neurotrophic factor in addition to the autonomic nervous system in mental
      stress response and insight in the immunomodulation by proopiomelanocortins.
      Novel strategies for therapy and prevention of chronicity may also result from
      understanding the role of increased secretion of nerve growth factor in atopic
      eczema and psoriasis.

PMID- 11964725
TI  - Origin and migratory properties of dendritic cells in the skin.
AB  - The professional antigen presenting cells of the skin, namely Langerhans cells
      and dermal dendritic cells, are continuously exposed to environmental stimuli.
      The population of antigen-carrying dendritic cells that migrates from this site
      to the draining lymph nodes is highly dynamic, and its density, composition and
      function changes as a consequence of dendritic cell recruitment and activation in
      tissues, as well as interactions with T lymphocytes in the specialized lymph node
      microenvironments. Therefore dendritic cells within the skin are the key
      regulators of both quantitative and qualitative aspects of immune responses to
      local antigenic challenge.

PMID- 11964726
TI  - Mastocytosis.
AB  - Mastocytosis is defined by a pathological increase in mast cell numbers in
      tissues. Recent clinical observations on rare manifestations highlight the
      diversity of this disease. The diagnosis is now aided by new surrogate markers.
      At the molecular level, recent studies have reinforced the role of activating
      mutations in KIT in the etiology of mastocytosis. These findings provide a
      conceptual basis for the development for new therapeutic strategies.

PMID- 11964727
TI  - The role of lymphocytes in healthy and eczematous skin.
AB  - Eczema is a heterogeneous disease and the pathophysiological mechanism should be
      clarified in each disease. Allergic contact dermatitis and atopic dermatitis are
      representative diseases showing eczematous reaction. A major player in both
      allergic contact dermatitis and atopic dermatitis is skin-specific T lymphocytes.
      The significance of these T lymphocytes, especially the expression of cutaneous
      lymphocyte-associated antigen on T helper cells types 1 and 2, and its counter
      receptor on vascular endothelial cells needs further investigation. The evidence
      showing that infiltrating T cells participate in the formation of eczematous
      reaction through Fas-induced apoptosis is important in our understanding of
      eczematous reactions and also for treatment.

PMID- 11964728
TI  - Molecular events occurring behind ultraviolet-induced skin inflammation.
AB  - We reviewed a recent advance in the studies of the molecular mechanisms for
      'ultraviolet responses', paying special attention to two transcription factors,
      nuclear factor kappa B and p53, and to a balance noted between an anti-apoptotic
      phosphatidylinositol 3-kinase-Akt pathway and its inhibitory ceramide-caveolin-1
      pathway. These studies were mostly carried out using in vitro or animal models.
      On the basis of these results, we determined that phase by phase molecular events
      clarified in these studies correspond well with the three phases of ultraviolet
      induced inflammation observed, i.e. the early vasodilatory phase, the second
      inflammatory phase in which many inflammatory cells such as neutrophils and T
      cells accumulate in the skin, and the last regressive phase based on several anti
      inflammatory events.

PMID- 11964730
TI  - Advances in ocular allergy: basic mechanisms, clinical patterns and new
      therapies.
AB  - Ocular allergy presents unsolved mysteries in molecular and cellular mechanisms,
      and at the same time continues to challenge ophthalmologists daily in a wide
      array of disease forms. The recent understanding of the key role of the T helper
      type 2 cytokines, adhesion molecules and chemokines may provide future avenues
      for pharmacological targeting of releasable inflammatory mediators. More potent
      topical mast cell stabilizers and H1 receptor antagonists have become
      commercially available for the management of the prevalent and benign forms of
      allergic conjunctivitis. Immunostimulatory DNA sequences present an innovative
      and promising route for the treatment of ocular allergy, but clinical studies are
      needed to demonstrate their efficacy in humans. Surgical methods are suggested to
      reconstruct the ocular surface in the sight-threatening diseases vernal
      keratoconjunctivitis and atopic keratoconjunctivitis. This review presents an
      update of the major advances in both the basic mechanisms and clinical and
      therapeutic aspects of ocular allergic diseases that were reported during the
      past year.

PMID- 11964729
TI  - Keratinocytes in epidermal immune responses.
AB  - Recent studies have advanced our understanding that the regulation of immune
      responses is not only confined to immunocompetent cells. Upon stimulation,
      keratinocytes are capable of releasing various factors and expressing receptors
      that are significantly involved in immunoregulation. Dysregulation and the
      abnormal production of cytokines and other inflammatory mediators as well as
      their receptors can be observed in various skin diseases. An understanding of
      keratinocytes as important regulators of the skin immune system opens new
      opportunities for the treatment of various skin diseases.

PMID- 11964731
TI  - Recombination activating gene and its defects.
AB  - Mutations in recombination activating genes cause a spectrum of severe
      immunodeficiencies ranging from T-B severe combined immunodeficiency to Omenn
      syndrome (a particular type of severe combined immunodeficiency presenting a T+ B
      profile). Although environmental factors and genetic background could also
      contribute to the genesis of this pathological condition, a residual
      recombination activating gene activity allowing for a few recombinational events
      to occur, is the first determinant of this variability in the clinical picture.

PMID- 11964732
TI  - Gene therapy for primary immune deficiencies.
AB  - Primary immunodeficiency diseases have been important targets of corrective gene
      transfer approaches since the very early days of gene therapy. The potential for
      selective survival advantage of gene-corrected cells over populations carrying
      the mutated, causative gene translates into the possibility of obtaining clinical
      meaningful results in patients with primary immunodeficiency diseases even if
      levels of gene transfer are low. This critical prospect has fueled the interest
      of researchers since the mid-1980s and has recently determined the success of a
      clinical trial of gene therapy for X-linked severe combined immunodeficiency.

PMID- 11964733
TI  - Mycobacterial diseases in primary immunodeficiencies.
AB  - Primary immunodeficiency diseases comprise over 100 conditions, each associated
      with a variety of viral, bacterial, fungal and protozoan infections. M.
      tuberculosis and less virulent mycobacteria, such as bacille Calmette-Guerin
      vaccines and environmental non-tuberculous mycobacteria, may cause severe disease
      in patients with primary immunodeficiency diseases. However, no previous review
      has dealt with the issue of which primary immunodeficiency diseases predispose
      affected individuals to mycobacterial disease. This information is very useful,
      not only increasing our understanding of human immunity to mycobacteria, but also
      for the diagnostic investigation of patients with mycobacteriosis. We review here
      the medical literature on cases of mycobacterial disease in patients with primary
      immunodeficiency diseases.

PMID- 11964734
TI  - Cellular and molecular pathogenesis of X-linked lymphoproliferative disease.
AB  - In the past few years important advances have been made in the understanding of
      the molecular mechanisms leading to X-linked lymphoproliferative disease (XLP).
      It has been possible to identify the gene defective in XLP and to demonstrate
      that, in normal individuals, it encodes the Src homology 2 domain-containing
      protein 1 A (SH2D1A) that plays a crucial role in signaling via a number of
      surface molecules expressed by cells of the immune system. At present a variety
      of mutations have been identified that result in lack of defective SH2D1A
      molecules. Importantly, it has recently been demonstrated that lack of SH2D1A
      affects the function of surface molecules that are involved in the mechanism of
      natural killer-mediated recognition and killing of Epstein-Barr virus-infected B
      cells.

PMID- 11964735
TI  - Terminal defects of B lymphocyte differentiation.
AB  - In humans several abnormalities can occur during terminal B cell differentiation,
      leading to primary humoral immunodeficiencies. A recent study provided evidence
      of a qualitative defect of the affinity antibody maturation in some patients
      affected with common variable immunodeficiency syndrome, the molecular basis of
      which remains unknown. Several genetic defects in class switch recombination
      leading to a hyper-IgM syndrome have recently been delineated. Besides the well
      known role of CD40-CD40 ligand interaction, they definitively demonstrate the
      requirement of CD40-mediated nuclear factor kappa B activation and the essential
      role of a newly described molecule, the activation-induced cytidine deaminase, in
      B cell terminal differentiation.

PMID- 11964736
TI  - Linking cellular activation to cytoskeletal reorganization: Wiskott-Aldrich
      syndrome as a model.
AB  - The Wiskott-Aldrich syndrome is an inherited X-linked disorder characterized by
      immune deficiency, eczema, and thrombocytopenia with small platelets. The mutated
      protein, Wiskott-Aldrich syndrome protein, is an activator of actin cytoskeletal
      reorganization in hematopoietic cells. Members of the Wiskott-Aldrich syndrome
      protein family are being shown to be key integrators of cell signalling and
      cytoskeletal organization in many eukaryotic cell types. This review focuses on
      recent discoveries that reveal in increasing detail how Wiskott-Aldrich syndrome
      protein and its related proteins operate.

PMID- 11964737
TI  - Novel aspects of phagocytic cell disorders.
AB  - This review highlights the various numerical and functional defects in the
      phagocyte system. It mainly focuses on newly discovered genetic defects in the
      system and the role played by these defects in the clinical symptoms presented by
      patients. Novel therapeutic modalities to treat phagocyte abnormalities, which
      are currently under clinical trials, are also discussed.

PMID- 11964738
TI  - Immunologic treatment of allergic diseases.

PMID- 11964739
TI  - Primary prevention of atopic asthma.
AB  - Current recommendations given for primary prevention of allergic asthma often
      include advice on how to reduce exposure to inhalant allergens early in life.
      There is little support for such advice, however. On the contrary, recent studies
      indicate that extensive allergen exposure may actually reduce the likelihood of
      developing allergic asthma. However, recent studies indicate possible future
      venues for primary allergy prevention through immune modulation. This may
      possibly be achieved by stimulating the maturation of the immune system early in
      life by altering the microbial gut flora or by recently developed
      immunomodulatory Th2 antagonists. In the meantime, the avoidance of exposure to
      tobacco smoke remains the only recommendation that is reasonably well documented
      by evidence-based medicine, while allergen avoidance in primary prevention is
      not.

PMID- 11964740
TI  - Can knowledge of the molecular structure of allergens improve immunotherapy?
AB  - Conventional immunotherapy may be associated with the development of adverse
      reactions, including anaphylaxis, due to the use of increasing doses of allergen.
      Standardization of extracts is necessary in order to assess the correct amount of
      allergen administered. In recent years, increased knowledge on the molecular
      structure of allergens has allowed the development of novel alternatives for
      immunotherapy. Initially, allergens were cloned and expressed as recombinant
      proteins in eukaryotic and prokaryotic systems. Crystallization of the purified
      proteins led to the elucidation of the tertiary structure of the allergen.
      Molecular biology techniques were used to construct modified allergens whose new
      IgE binding properties were studied. IgE antibody mapping combined with molecular
      modeling has allowed the recognition of IgE binding sites on the surface of the
      molecule. This information has been applied to the engineering of new modified
      allergens, with and without adjuvants, that retain immunogenicity but with
      reduced allergenicity. The use of these molecules for immunotherapy should allow
      the administration of greater doses of allergen, without the undesired side
      effects characteristic of conventional immunotherapy.

PMID- 11964741
TI  - Cytokine modulators for allergic diseases.
AB  - Cytokines play a critical role in orchestrating and perpetuating inflammation in
      allergic diseases and several specific cytokine inhibitors now in development for
      the treatment of asthma and other allergic diseases. The effects of inhibiting
      the T helper 2 cytokines interleukin-5, interleukin-13 and interleukin-9 are
      discussed, together with inhibition of tumor necrosis factor-alpha. Inhibitory
      cytokines, such as interleukin-10, interferons and interleukin-12, are also being
      considered in the treatment of allergic diseases.

PMID- 11964742
TI  - Antichemokine immunotherapy for allergic diseases.
AB  - Chemokines have emerged as critical regulators of leukocyte function and as such
      represent attractive new targets for the therapy of allergic diseases. Recent
      studies have revealed important roles for the chemokine family in both the
      afferent and efferent limbs of the immune system, orchestrating and integrating
      innate and acquired immune responses. A subset of chemokines including eotaxin-1
      (also called CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26), MCP (monocyte
      chemoattractant protein)-3 (CCL7), MCP (monocyte chemoattractant protein)-4
      (CCL13), TARC (thymus- and activation-regulated chemokine) (CCL17), and MDC
      (macrophage-derived chemokine) (CCL22) are highly expressed in allergic
      inflammation and are regulated by T helper type 2 cytokines. Receptors for these
      chemokines, including CCR3 (CC chemokine receptor 3), CCR4 (CC chemokine receptor
      4) and CCR8 (CC chemokine receptor 8) are expressed on key leukocytes associated
      with allergic inflammation, such as T helper type 2 cells, eosinophils, mast
      cells and basophils, establishing a subset of chemokine/chemokine receptors
      potentially important in allergic inflammation. Recent data using inhibitory
      antibodies and chemokine antagonists support the concept that interfering with
      this subset of chemokines and their receptors represents a new approach to
      allergy immunotherapy.

PMID- 11964743
TI  - Epithelial cells as immunoregulators in allergic airway diseases.

PMID- 11964744
TI  - Update of growth effects of inhaled and intranasal corticosteroids.
AB  - A small effect (approximately 1 cm) of inhaled and intranasal corticosteroids on
      the 1 year growth of children with asthma and allergic rhinitis, respectively,
      has been reported in studies published during the past 10 years. Literature
      published during the past year confirmed the effect, but provided additional and
      novel information on the effects of longer-term (over 1 year) treatment,
      particularly with inhaled corticosteroids. This information is timely, because
      the longer-term effect size and duration were previously unknown, and the
      findings have major implications for the content of the safety discussion between
      caregivers and the parents of children with asthma or allergic rhinitis. The
      results of these studies provide very reassuring information about the longer
      term safety of the use of inhaled corticosteroids in children with asthma.
      Limited evidence has also supported the notion that intranasal corticosteroids
      have no longer-term effects on growth. The possibility of an idiosyncratic
      (versus global) effect received conflicting support in recent literature. The
      risk of growth retardation can be lessened and managed by the employment of
      several simple strategies: (i) monitor growth; (ii) use minimal effective dose;
      and (iii) optimize steroid-sparing strategies. Communication with
      patients/parents about this possible side-effect, as well as the adverse
      consequences of the non-use of inhaled and intranasal corticosteroids, is
      essential to minimize any possible negative impact on adherence. Children whose
      disease severity warrants inhaled or intranasal corticosteroid therapy should not
      be denied their benefits on the basis of this safety consideration.

PMID- 11964745
TI  - Upper airway neurogenic mechanisms.
AB  - Stimulation of the nasal sensory nerves leads to sensations of pain and
      stuffiness. Type C nociceptive nerve releases neuropeptides including substance P
      and calcitonin gene related peptides that increase plasma extravasation and
      glandular secretion. This axonal response acts as an immediate protective mucosal
      defense mechanism. Recruited parasympathetic reflexes cause submucosal gland
      secretion via acetylcholine and muscarinic M(3) receptors. Itching, sneezing, and
      other avoidance behaviors rapidly clear the offending agents from the upper
      airways and protect the lower airways. Dysfunction of these nerves may contribute
      to allergic rhinitis, infectious rhinitis, nasal hyperresponsiveness, and
      possibly sinusitis. Sympathetic arterial vasoconstriction reduces mucosal blood
      flow, sinusoidal filling, and mucosal thickness, and so restores nasal patency.
      Loss of sympathetic tone may contribute to some chronic, nonallergic
      rhinopathies. Human axon responses differ from those in animals, an important
      distinction that limits extrapolation from other species.

PMID- 11964746
TI  - The link between allergic rhinitis and otitis media.
AB  - Past studies implicated allergy in the pathogenesis of otitis media. However,
      definitive proof of the assertion is lacking. Epidemiologic studies, including
      one recently published by Rylander and Megevand, consistently identify allergy as
      a risk factor for otitis media. Also, higher than expected frequencies of allergy
      are reported for patients with otitis media, but it is unclear if this is an
      epiphenomenon associated with referral bias. This possibility is exemplified by
      the results of two reviewed papers where Velepic and colleagues reported a 25%
      prevalence of allergy in otitis media patients while Alles and colleagues
      reported a prevalence of 89%. Other studies documented biochemical components of
      allergic inflammation in the effusions recovered from children with otitis media,
      and Hurst and colleagues published a recent paper continuing on that theme.
      However, it is not known if a local allergic reaction is required for the
      production of these components and if they are produced exclusive of other
      inflammatory products. Three published studies explored mechanisms by which
      allergy could cause otitis media. Tikkanen and colleagues reexamined at age 10 a
      group of 56 subjects with previously diagnosed milk allergy and showed that
      despite decreased reactivity to milk protein a high prevalence of otitis media
      was retained. This suggests that it is the allergic condition, not the specific
      allergy to milk that increases otitis media risk. Downs and colleagues exposed
      the middle ears of rats to histamine and provoked changes in the pressure
      regulating and clearance functions of the Eustachian tube. Those changes could
      prolong an otitis media episode, but middle ear histamine is not limited to the
      allergic condition. Gentile and colleagues challenged the nose of allergic and
      nonallergic subjects with histamine followed by interleukin-6 or placebo and
      measured nasal, pulmonary, Eustachian tube and middle ear functions. Interleukin
      6 did not change the Eustachian tube or middle ear functions but did cause
      increased secretions in allergic patients.

PMID- 11964747
TI  - Asthma: more than an inflammatory disease.

PMID- 11964748
TI  - T helper type 1 cells in asthma: friend or foe?
AB  - A large body of research supports a pathogenic role for T helper 2 cells in
      asthma, although T helper 1 cell-type responses may also contribute. Using the
      principle of T helper cell cross-regulation, investigators have attempted to
      regulate the pathological effects of T helper 2 cells using regimens that may
      promote T helper 1 cell-type inflammation. In this review, we propose that the
      use of factors that promote T helper 1 cell differentiation and activation to
      treat asthma may be counterproductive, and that alternate regulatory approaches
      should be explored.

PMID- 11964749
TI  - Modulation of calcium homeostasis as a mechanism for altering smooth muscle
      responsiveness in asthma.
AB  - Airway hyperresponsiveness remains a defining characteristic of asthma.
      Traditional views assert that airway smooth muscle is an important structural
      effector cell in the bronchi that modulates bronchomotor tone induced by
      contractile agonists. New evidence, however, suggests that abnormalities in
      airway smooth muscle functions, induced by variety of extracellular stimuli, may
      play an important role in the development of airway hyperresponsiveness. Studies
      using isolated bronchial preparations or cultured cells show that inflammatory
      mediators and cytokines may alter calcium homeostasis in airway smooth muscle and
      render the cells nonspecifically hyperreactive to agonists.

PMID- 11964750
TI  - Factors controlling smooth muscle proliferation and airway remodelling.
AB  - It is clear that airway smooth muscle plays an important role in the
      hyperresponsiveness and remodelling that occur in the asthmatic airway. This is
      by virtue of its roles as a contractile cell, a cell that undergoes proliferation
      as part of the inflammatory response, a cell that actively participates in the
      inflammatory response via the production of cytokines and chemokines, and perhaps
      as a cell that undergoes migration. Now that airway smooth muscle cells cultured
      from asthmatic patients have been studied in vitro, it is apparent that there is
      an abnormality in the growth of these cells such that they grow more rapidly than
      cells derived from nonasthmatic patients. This raises the possibility of
      identifying the exact point(s) in the signal transduction pathways at which this
      abnormality occurs. To do this it is necessary to define precisely the mitogenic
      pathways that lead to proliferation in the airway smooth muscle cell, and this
      information is accumulating rapidly. The possibility is raised for new
      therapeutic targets that are aimed specifically at the airway smooth muscle,
      leading to an effective method for reversing or preventing the airway remodelling
      that accompanies chronic severe asthma.

PMID- 11964752
TI  - Selective phosphodiesterase inhibitors for the treatment of asthma and chronic
      obstructive pulmonary disease.
AB  - Phosphodiesterase type 4 plays an important role in modulating the activity of
      cells that are involved in the inflammatory processes occurring in chronic
      obstructive pulmonary disease and asthma. During the past decade, interest has
      focused on the development of selective inhibitors of phosphodiesterase-4, in an
      attempt to generate new treatment modalities that control airway inflammation not
      only in patients with asthma but also in those with chronic obstructive pulmonary
      disease. The aim of the present review is to discuss the results of recent
      clinical intervention studies with phosphodiesterase-4 inhibitors in patients
      with asthma or chronic obstructive pulmonary disease.

PMID- 11964751
TI  - Are antihistamines useful in managing asthma?
AB  - There continues to be a great deal of interest in the anti-asthmatic role of
      antihistamines. Antihistamines have recently been shown to have anti-inflammatory
      properties that are more extensive than simply the blocking of histamine
      receptors. For example, new evidence suggests that the suppression of cell
      adhesion molecule expression occurs with these drugs. The anti-inflammatory and
      anti-asthmatic effects of antihistamines have been evaluated in patients with
      both allergic asthma and rhinitis, given the established association between
      allergic inflammation of the upper and lower airways, with evidence to suggest
      that antihistamines have clinically relevant anti-asthmatic properties. As well
      as conferring benefits in asthma symptom control and the measurement of lung
      function, studies assessing the effect of histamine receptor antagonists on
      bronchial hyperresponsiveness suggest that there is bronchoprotection during both
      methacholine and mannitol challenges. Recently, there has also been considerable
      interest in the effect of combining an antihistamine with a leukotriene receptor
      antagonist. This combination has an anti-asthmatic effect that is greater than
      that of either drug given alone and may be comparable to inhaled corticosteroid
      therapy.

PMID- 11964753
TI  - DNA therapy for asthma.
AB  - Asthma therapy, like other therapies, has been moving towards a molecular basis
      for several years. This year, there have been several preclinical studies
      published which utilize attributes or facets of DNA to address asthma
      therapeutics. These include antisense oligonucleotides (against the nuclear
      transcription factor GATA-3 and the mast cell chemotactic agent, stem cell
      factor), gene transfer (of interleukin-18, both by plasmid and viral vectors),
      and CpG oligodeoxynucleotides (which suppress Th2 and stimulate Th1 responses).
      No clinical experience has yet been reported for any of these areas of research
      in asthma, but clinical trials are ongoing utilizing CpG oligonucleotides.

PMID- 11964754
TI  - Advances in acid anhydride induced occupational asthma.
AB  - The acid anhydrides have been signal occupational agents for study because of
      their inherent and complex biological activity and the wide range of associated
      occupational airway disease that is manifest in exposed workers in a variety of
      occupational settings. This year in review has shed light on many of the
      complexities of anhydride exposure, biologic reactivity and airway disease.

PMID- 11964755
TI  - Utilization of pulmonary function measurements in the assessment of occupational
      asthma.
AB  - Lung function assessments that include spirometry and bronchial responsiveness
      are now often coupled to immunological assessment and an evaluation of
      inflammation in the investigation of occupational asthma. For diagnostic
      purposes, evidence points out that specific inhalation challenges are the gold
      standard, as previously suspected. In the epidemiological setting, both
      spirometry and bronchial responsiveness are feasible and safe. The role of lung
      function assessments in surveillance programmes is still open to discussion.

PMID- 11964756
TI  - Occupational asthma and allergy in the detergent industry: new developments.
AB  - This review highlights the latest developments in the control of enzyme-induced
      occupational asthma and allergy (rhinitis and conjunctivitis) in the detergent
      industry. The industry has developed guidelines for the safe handling of enzymes
      in order to reduce the risk of occupational allergy and asthma. Those
      manufacturing facilities that follow all of the guidelines enjoy very low or no
      cases of asthma and allergy among workers exposed to enzymes. The key to the
      success of the management of enzyme-induced allergy and asthma is prospective
      surveillance for the development of enzyme-specific IgE antibody before the onset
      of allergic symptoms. This allows for continuing interventions to reduce
      exposures, so as to minimize or eliminate those associated with symptoms. Workers
      with IgE to enzymes can still continue to work in the industry symptom-free for
      their entire career. This indicates that exposures needed to induce sensitization
      are different and probably lower than exposures needed to elicit enzyme allergic
      symptoms. The experience of the detergent enzyme industry in controlling
      occupational allergens can be applied to other industries. The detergent enzyme
      story can be viewed as a model for the control of type 1 protein allergens in the
      workplace.

PMID- 11964757
TI  - Spider-mite allergy and asthma in fruit growers.
AB  - Asthma and allergic diseases caused by domestic mites such as house dust mites
      and storage mites are major health problems worldwide. In contrast to domestic
      mites, spider mites are outdoor phytophagous mites causing significant damage to
      fruit leaves throughout the world. After several case reports of spider mite
      induced asthma and allergy, cross-sectional surveys have demonstrated that spider
      mites are important allergens in the development of asthma and rhinitis in fruit
      farmers. Interestingly, epidemiological surveys have also demonstrated that
      spider mites are common sensitizing allergens that are related to the prevalence
      of asthma and rhinitis, even in the non-farming population exposed to spider
      mites. Protein analysis has demonstrated that crude extracts derived from spider
      mites contain several major allergens, and that N-terminal amino acid sequencing
      of the major allergens is not homologous with any previously characterized
      domestic mite allergens, suggesting that major allergens derived from spider
      mites are unique in terms of cross-reactivity to domestic mites. Taken together,
      these findings suggest that spider mites are important allergens in the
      development of asthma among the exposed non-farming population as well as among
      fruit farmers themselves, and that allergens derived from spider mites may be
      novel allergens.

PMID- 11964758
TI  - Non-invasive assessment of airway inflammation in occupational lung diseases.
AB  - The clinical investigation of occupational asthma is currently based on the
      demonstration of functional changes after exposure to occupational agents, but it
      does not yet include any monitoring of airway inflammation, one of the hallmarks
      of this disease. Methods permitting a non-invasive assessment of airway
      inflammation, such as induced sputum and exhaled nitric oxide, are currently
      under investigation for research purposes in occupational asthma. Their role in
      clinical practice has not yet been established. The advantages and limitations of
      these methods for occupational airway diseases, and more particularly
      occupational asthma, are discussed in this review.

PMID- 11964759
TI  - Chronic obstructive lung diseases and occupational exposure.
AB  - The scope of this review is to highlight important and interesting articles in
      the field of the epidemiology of chronic obstructive pulmonary disease and
      occupational exposure. Relevant information from the literature published within
      the past year, either on general population samples or on workplaces, indicates
      that a substantial proportion of asthma and chronic obstructive pulmonary
      diseases are work related. Methods of investigation include self-reported or
      interview-obtained questionnaires, job title and job exposure matrix, as well as
      voluntary or mandatory notifications. Furthermore, data on lung function and
      immunological tests are available. Specific settings and agents are quoted that
      have been indicated or confirmed as being linked to chronic obstructive pulmonary
      disease. In conclusion, occupational exposure to dusts, chemicals and gases will
      be considered an established, or supported by good evidence, risk factor for
      chronic obstructive pulmonary disease. The implications of this substantial
      occupational contribution to asthma and chronic obstructive pulmonary disease
      must be considered in research planning, in public policy decision-making, and in
      clinical practice.

PMID- 11964760
TI  - Persistence of airway responsiveness to occupational agents: what does it matter?
AB  - In the majority of workers with occupational asthma, the disease remains active
      even several years after removal from exposure or diminution of the levels of
      exposure to the causal agent. Only 25% or so normalize their lung function and
      their bronchial responsiveness to nonspecific agents. The aim of this review is
      to present recent findings illustrating the persistence of specific bronchial
      responsiveness and the associated factors in workers who apparently have
      recovered from occupational asthma. This subject is also examined from a
      socioeconomic perspective.

PMID- 11964761
TI  - Pediatric allergy.

PMID- 11964762
TI  - Do animals on the farm and in the home reduce the risk of pediatric atopy?
AB  - Recent evidence suggests that proximity to pets and farm animals early in life
      may decrease the risk of developing atopy. Studies investigating the etiology of
      atopy and asthma have been especially challenging due to difficulties in
      ascertaining and classifying incident cases. Nevertheless, cross-sectional and
      cohort studies described in this paper reported across various populations, among
      children and adults, tended to demonstrate inverse associations between the
      presence of indoor cats and dogs or frequent exposure to livestock during the
      first years of life and sensitization to pet and pollen allergens, hay fever, and
      to a lesser degree, asthma. The biological mechanisms of this protection is
      unknown, as are the factors associated with pet keeping and livestock farming
      that may play a role. In the meantime, it appears that counseling prospective
      parents that avoidance of exposure to animals in the first years of life will
      prevent atopy may not be sage advice.

PMID- 11964763
TI  - Endotoxin, atopy and asthma.
AB  - Endotoxin is infamous for its ability to exacerbate existing allergy and asthma
      symptoms. Current research supports this phenomenon, demonstrating its
      significance in the home, as well as in the workplace. At the same time, evidence
      is emerging that exposure to endotoxin may drive immune development away from the
      T-helper lymphocyte type 2-mediated allergy and asthma profile. This fits in
      nicely with the 'hygiene hypothesis', which attributes the past century's rise in
      allergy and asthma to a reduction in microbial burden. Indeed, infections have
      been associated with less atopy and asthma. Recent investigations have suggested
      that naturally-occurring non-infectious exposure to microbial components such as
      endotoxin might mitigate atopy and asthma as well.

PMID- 11964764
TI  - Novel insights into class switch recombination.
AB  - The discovery of activation-induced cytidine deaminase, a putative RNA editing
      enzyme essential for both class switch recombination and somatic hypermutation,
      marked the field of isotype switching studies in the year 2000. More recent work
      from the same group now highlights some essential mechanistic aspects of the
      switch recombination process. In particular, much has been learnt about the
      relationship between transcription and recombination and the transcriptional
      competence of intronic promoters on looped-out circular DNA uncoupled from the
      proximal and distal enhancers. These findings have far-reaching implications,
      particularly for studies of class switch recombination in tissues. Although these
      important advances do not directly relate to interleukin-4-dependent
      immunoglobulin E switching, the conceptual and experimental tools developed
      through these studies are certain to foster progress in the immunoglobulin E
      field.

PMID- 11964765
TI  - Fresh starting points for HIV's second century.

PMID- 11964766
TI  - Mitochondrial toxicity of nucleoside analogue reverse transcriptase inhibitors: a
      looming obstacle for long-term antiretroviral therapy?
AB  - Nucleoside reverse transcriptase inhibitors suppress HIV replication by blocking
      reverse transcriptase, an RNA-dependent DNA polymerase. These drugs can also
      affect cellular and mitochondrial DNA polymerases. Mitochondrial DNA polymerase
      gamma is particularly sensitive to nucleoside reverse transcriptase inhibitors,
      and the majority of adverse effects caused by nucleoside reverse transcriptase
      inhibitors are most likely caused by mitochondrial dysfunction. This article
      reviews the recent clinical implications of nucleoside reverse transcriptase
      inhibitor-induced mitochondrial toxicity and discusses options for management.

PMID- 11964767
TI  - The immune system: our best antiretroviral.
AB  - A better understanding of the potent immune responses elicited by HIV before
      infected patients become immunocompromised should enable therapeutic
      immunomodulation to prevent disease progression. We review the nature of the
      immune response in HIV infected long-term nonprogressor patients; how and why the
      immune system fails; and whether it may be feasible to harness the immune system
      to control viraemia and extend the asymptomatic period in HIV infected persons.
      Finally we discuss the possibility of inducing sterilizing immunity to enable the
      host to rid itself of the virus.

PMID- 11964768
TI  - Considerations in the choice of protease inhibitor-sparing regimens in initial
      therapy for HIV-1 infection.
AB  - The current standard of care for initial antiretroviral therapy is a combination
      of 2 nucleoside analogues with a third agent, a protease inhibitor (PI), a non
      nucleoside reverse transcriptase inhibitor or a third nucleoside analogue. Recent
      data heralding the arrival of potent PI-sparing regimens for initial anti
      retroviral therapy and concerns regarding PI-related metabolic disturbances have
      led to significant shifts in treatment practices. Protease inhibitor-sparing
      regimens with optimal antiviral activity may have several advantages over PI
      based therapy for initial or prolonged therapy. These advantages include more
      convenient, non-food dependent dosing regimens, lower tablet volume, fewer drug
      interactions, central nervous system penetration and the maintenance of PIs as an
      option for second line therapy. However, no data currently exist directly
      comparing triple therapy regimens based on the three leading PI-sparing agents,
      efavirenz, nevirapine or abacavir. All these agents have been compared in
      randomized controlled studies in treatment naive patients to triple therapy with
      the PI indinavir. In these studies, similar responses to indinavir were observed
      with nevirapine or abacavir regimens, whereas superiority was observed with
      efavirenz. Limited data in high viral load patients treated with nevirapine based
      regimens currently exist. However, the superiority of efavirenz over indinavir
      based regimens was also observed in comparative data in this patient subset. PI
      sparing approaches appear generally well tolerated with few individuals
      discontinuing in clinical studies due to adverse drug events. The majority of
      adverse events with efavirenz and nevirapine occur within the first month, are
      predictable and are manageable without therapy interruption. Similarly, apart
      from a rare (3%) hypersensitivity reaction, which requires therapy cessation
      without rechallenge, adverse effects with abacavir are uncommon.

PMID- 11964769
TI  - Sexually transmitted diseases.

PMID- 11964770
TI  - The genome sequence of Treponema pallidum, the syphilis spirochete: will
      clinicians benefit?
AB  - The sequence of the Treponema pallidum genome was completed in July 1998,
      yielding a wealth of new information regarding the enigmatic spirochete that
      causes syphilis and related treponematoses. By providing the sequences and
      predicted functions of over 1000 genes, the genome sequence will greatly
      facilitate research on the genetic characteristics, physiology, antigenic
      structure, and pathogenesis of this organism. These advances are, in turn,
      expected to promote the refinement of conditions for in-vitro culture, an
      improvement of diagnostic tests, the development of effective vaccines, and an
      improved understanding of treponemal disease pathogenesis and manifestations.

PMID- 11964771
TI  - Biology of trichomonosis.
AB  - Trichomonas vaginalis is emerging as a major pathogen of men and women and is
      associated with serious health consequences. Advances in diagnosis and treatment
      are presented. The complexity of trichomonad pathogenesis is illustrated in the
      interaction of this parasite with human cells, tissues and the immune system. It
      is now becoming evident that the interaction of trichomonads with the host is
      frequently modulated by environmental signals. The molecular biology of
      trichomonads is still in its infancy, but analysis of genes, genomic structure
      and transcriptional mechanisms suggest that trichomonads combine both prokaryotic
      and eukaryotic features. Evidence for the ancient divergence of trichomonads from
      other eukaryotic lineages is discussed.

PMID- 11964772
TI  - Sexually transmitted infections in teenagers.
AB  - Prevention of sexually transmitted infection in teenagers is a high priority. The
      introduction of non-invasive methods for diagnostic testing of Chlamydia
      trachomatis and Neisseria gonorrhoeae has enabled screening for these sexually
      transmitted micro-organisms in a range of community-based settings among
      populations at high risk, such as teenagers, who do not readily access existing
      sexual health services.

PMID- 11964773
TI  - Postexposure to HIV prophylaxis.
AB  - Since the reports of an international case-control study during the period 1995
      1997, further evidence has accumulated supporting the use of postexposure therapy
      with antiretrovirals. This includes evidence from vertical transmission studies
      with both zidovudine and nevirapine, and animal model data. Guidelines have been
      developed and revised for occupational postexposure prophylaxis provision, but
      there remains considerable debate over postexposure prophylaxis for
      nonoccupational (predominantly sexual) exposures.

PMID- 11964774
TI  - HIV, the skin and the impact of antiretroviral therapy.

PMID- 11964775
TI  - Retroviruses and psoriasis.
AB  - Psoriasis occurs with at least undiminished frequency in HIV infected
      individuals. The behaviour of psoriasis in HIV disease is of interest, both in
      terms of pathogenesis and therapy, because of the background of profound
      immunodysregulation. It is paradoxical that, while drugs that target T
      lymphocytes are effective in psoriasis, the condition should be exacerbated by
      HIV infection. Antiretroviral therapy may improve psoriasis in tandem with
      improvement in the overall clinical and virological condition of the patient. The
      aetiopathogenesis of psoriasis is unknown but genetic and environmental factors
      are thought to be involved. There are controversial issues regarding the
      immunological basis of psoriasis and the role of CD4+ versus CD8+ T lymphocytes.
      Current opinion favours an autoimmune basis for psoriasis, although the
      precipitating activating signal(s) within psoriatic plaques remains unknown. The
      immunodysregulation resulting from HIV infection may trigger psoriasis in those
      genetically predisposed by the Cw*0602 allele. Since CD8+ T cells recognize
      antigen in the context of class I molecules, the identification of a human
      leucocyte antigen class I association in HIV-associated psoriasis strengthens the
      argument for an important role for CD8+ T lymphocytes in the immunopathogenesis
      of psoriasis. HLA-Cw*0602 could act as a cross-reactive target for cytotoxic T
      lymphocytes responding to processed peptides from microorganisms. Human
      retrovirus-5 is a recently described, partially characterized retrovirus and has
      been implicated in the pathogenesis of psoriatic arthropathy but not psoriasis.

PMID- 11964776
TI  - Buruli ulcer.
AB  - Buruli ulcer (Mycobacterium ulcerans) is an emerging disease. The mode of
      transmission is still unknown. Mycobacterium ulcerans has been detected (by
      polymerase chain reaction) in water and water insects. Extensive surgery is still
      the main treatment. Recognition and excision - of the early nodular stage - is
      effective. The toxin, a polyketide, causes immunosuppression with potent
      inhibition of monocytes, T cells and nuclear factor kappa-B activation.

PMID- 11964777
TI  - Current status of immunization against anthrax: old vaccines may be here to stay
      for a while.
AB  - Anthrax vaccination has become a 'hot' topic. On the one hand, fears that Iraq
      holds secret caches of anthrax-based weaponry, that other countries may be
      developing or may have developed similar devices, or that hard-line groups may
      make their own anthrax-based devices for bioterrorist attacks have focused
      official attention on the need for means of protection, principally, though, for
      the military. On the other hand, the unsolved issues of the Gulf War illnesses
      have left elements of doubt in the minds of some as to the possible role of
      anthrax (among other) vaccines in this syndrome, and have drawn attention to the
      shortage of pre-clinical, clinical, pharmacological and safety data on the
      existing UK and US anthrax vaccines. In the middle are those hotly debating the
      US and Canadian policies of mandatory anthrax immunization for military personnel
      or, in the case of the UK policy of voluntary immunization, simply voting with
      their feet. Compounding matters have been the publicized failures of the US
      vaccine production facility and the less publicized UK problems of supply.
      Meanwhile, those in genuine at-risk occupations are left unsure whether, if they
      can get the vaccine at all, they really want it. Despite two decades of elegant
      science aimed at formulating alternative vaccines to overcome all the problems of
      efficacy, safety and supply, such an alternative is at least five years away, and
      the current status is that we must live with the old vaccines or not vaccinate.

PMID- 11964778
TI  - Fusarium infections of the skin.
AB  - Fusarium species are ubiquitous and may be found in the soil, air and on plants.
      Fusarium species can cause mycotoxicosis in humans following ingestion of food
      that has been colonized by the fungal organism. In humans, Fusarium species can
      also cause disease that is localized, focally invasive or disseminated. The
      pathogen generally affects immunocompromised individuals with infection of
      immunocompetent persons being rarely reported. Localized infection includes
      septic arthritis, endophthalmitis, osteomyelitis, cystitis and brain abscess. In
      these situations relatively good response may be expected following appropriate
      surgery and oral antifungal therapy. Disseminated infection occurs when two or
      more noncontiguous sites are involved. Over eighty cases have been reported, many
      of which had a hematologic malignancy including neutropenia. The species most
      commonly involved include Fusarium solani, Fusarium oxysporum, and Fusarium
      moniliforme (also termed F. verticillioides). The diagnosis of Fusarium infection
      may be made on histopathology, gram stain, mycology, blood culture, or serology.
      Portals of entry of disseminated infection include the respiratory tract, the
      gastrointestinal tract, and cutaneous sites.The skin can be an important and an
      early clue to diagnosis since cutaneous lesions may be observed at an early stage
      of the disease and in about seventy-five cases of disseminated Fusarium
      infection. Typical skin lesions may be painful red or violaceous nodules, the
      center of which often becomes ulcerated and covered by a black eschar. The
      multiple necrotizing lesions are often observed on the trunk and the extremities.
      Onychomycosis most commonly due to F. oxysporum or F. solani has been reported.
      The onychomycosis may be of several types: distal and lateral subungual (DLSO),
      white superficial (WSO), and proximal subungual (PSO). In proximal subungual
      onychomycosis there may be associated leukonychia and/or periungual inflammation.
      Patients with Fusarium onychomycosis have been cured following therapy with
      itraconazole, terbinafine, ciclopirox olamine lacquer, or topical antifungal
      agent. In other instances nail avulsion plus antifungal therapy has been
      successful. In patients with hematologic malignancy or bone marrow transplant,
      who may experience prolonged or severe neutropenia during the course of therapy,
      the skin and nails should be carefully examined and consideration given to
      treating potential infection sites that may serve as portals for systemic
      dissemination. When disseminated Fusarium infection is present therapy with
      antifungal agents has generally been disappointing with the chances of a
      successful resolution being enhanced if the neutropenia can be corrected in a
      timely manner.

PMID- 11964779
TI  - Cutaneous manifestations of Penicillium marneffei infection.
AB  - From an almost unknown disease 15 years ago, Penicillium marneffei has emerged to
      become one of the most common opportunistic fungal pathogens among HIV-infected
      patients in the endemic area of southern China and northern Thailand. The mode of
      infection is primarily airborne, with the reticuloendothelial system as the main
      target. Penicilliosis is a fatal disease and systemic antifungals are the
      mainstay of therapy. Direct and mycological examinations are sufficient to make a
      diagnosis and to differentiate P. marneffei from other opportunistic fungi,
      although advances in serodiagnosis may potentially enhance understanding of the
      pathogenesis and identification of early asymptomatic cases.

PMID- 11964781
TI  - New millennium: new antimicrobial agents for respiratory infections; but an old
      plea.

PMID- 11964780
TI  - Head lice: is there a solution?
AB  - Head lice is an old problem that won't go away. Infestation with the head louse
      Pediculus capitis is still common in school-aged children. The majority of
      information about this condition is based on anecdotal evidence. There is a
      definite need for the standardization of detection methods for diagnosis and
      epidemiological purposes, and for properly designed trials to ascertain the
      effectiveness of the different treatment methods available.

PMID- 11964782
TI  - Trends and significance of antimicrobial resistance in respiratory pathogens.
AB  - Although we have witnessed a dramatic increase in the prevalence of antimicrobial
      resistance in respiratory pathogens over the past few years, resistance has
      infrequently been associated with clinical failures. However, as the prevalence
      and degree of resistance increases in the beta-lactams and the fluoroquinolones,
      newly approved for respiratory infections, failures are likely to occur.

PMID- 11964783
TI  - Update: prevention and treatment of tuberculosis.
AB  - Tuberculosis remains one of the leading infectious disease killers globally. A
      significant reservoir of infected individuals and disease activity remains,
      particularly in the countries of the world which have the least economic
      resources to treat latent and active disease. This has set the stage, over the
      decades, for the development of multi-drug resistant isolates now easily spread
      around the world with increased trans-national migration.Tuberculosis treatment
      and control requires a global approach with international organizations such as
      the World Health Organization (WHO), and the International Union Against
      Tuberculosis and Lung Disease (IUATLD) overseeing National Tuberculosis Control
      Programs and seeking financial support from governmental as well as non
      governmental sources. Directly Observed Therapy Short Course (DOTS) and DOTS Plus
      remain the cornerstones in the treatment of drug sensitive and drug resistant
      diseases respectively.Research activity should focus in developing early
      diagnostic tools and drugs which would be able to effectively treat tuberculosis
      cases for shorter periods of time in the new millennium.

PMID- 11964784
TI  - Chlamydia pneumoniae respiratory infections.
AB  - Chlamydia pneumoniae is a significant cause of both upper and lower respiratory
      tract infections. The spectrum of diseases ranges from asymptomatic infection to
      serious disease, including severe pneumonia and exacerbations of chronic
      bronchitis requiring mechanical ventilation. There is increasing evidence of
      involvement of C. pneumoniae infection in bronchial asthma, and the role of this
      agent in immunocompromised patients has also begun to be appreciated.

PMID- 11964785
TI  - Update on acute otitis media.
AB  - The increase in drug-resistant Streptococcus pneumoniae has led to concerns about
      antibiotic resistance. Otitis media is the leading indication for antibiotic use
      in the United States. Evidence suggests that antibiotics do provide benefit to
      children with documented acute otitis media, and that carefully selected children
      may respond to shorter courses of antibiotics. Despite the increase in
      resistance, amoxicillin remains the drug of choice for acute otitis media even in
      areas with high levels of resistance. Pneumococcal conjugate vaccine and live
      attenuated influenza vaccine, which may be licensed in the future, will both have
      an impact on acute otitis media. During the next few years, these vaccines, along
      with more stringent diagnostic criteria, and more judicious use of antibiotics,
      may all contribute towards reducing the incidence of acute otitis media, the
      number of antibiotic prescriptions given and the adverse impact of antimicrobial
      resistance.

PMID- 11964786
TI  - Acute exacerbations of chronic bronchitis.
AB  - Acute exacerbations of chronic bronchitis are one of the major public health
      challenges. New data suggest that they will remain so for many years. Although
      the role of bacteria in the initiation and maintenance of bronchial inflammation,
      both during and between exacerbations, is well recognized, studies of the long
      term effects of therapy are few and inadequate, and the nature of the
      relationship with disease progression is largely unknown. Data are beginning to
      emerge that firmly link bacterial inflammation and progressive disease with
      physiological and functional disability. Methods are being developed to provide
      integrated, uncomplicated and reproducible assessments of health-related quality
      of life. These may prove fundamental to the proper investigation of new treatment
      modalities. Among the newer antibacterial agents, fluoroquinolones have received
      most investigative attention, regrettably usually without providing clinical
      confirmation of their obvious superiority in vitro and of their pharmacokinetic
      and related pharmacodynamic properties. New trial designs need to address an
      integrated outcome analysis, with the assessment of long-term benefit and
      pharmaco-economic monitoring. More antibacterial agents are available at the
      millennium than ever before. After 50 years, it would be preferable if we knew a
      little more about their role in this complex disease.

PMID- 11964787
TI  - Differential white blood cell count: underutilized or overrated.

PMID- 11964788
TI  - Factors that influence T helper cell response to infection.
AB  - Many factors influence the decision of a precursor T helper cell to become either
      a type 1 or type 2 cell. These comprise pathogen-defined factors such as the
      nature and quantity of the pathogen, the route of infection, the influence of
      immunomodulatory components and of concomitant infections, as well as host
      defined factors including genetic predisposition, the number of responding T
      cells, the major histocompatibility complex haplotype of the individual, the
      nature of the antigen presenting cells involved and the cytokine environment of
      the T cells during and following activation. Understanding how such factors
      influence immune class regulation is fundamental to understanding the pathology
      of infectious diseases.

PMID- 11964789
TI  - Non-antibiotic therapy for Clostridium difficile infection.
AB  - Treatment of Clostridium difficile infection with metronidazole or vancomycin is
      successful in the majority of cases, but relapse occurs in 15% to 20% of
      patients, and in some the infection can remain chronic for months or years. The
      use of non-antibiotic therapies for this infection is theoretically attractive,
      as they would enable the normal colonic microflora to be reconstituted which is a
      requirement for permanent eradication of this pathogen. Over the past decade a
      number of non-antibiotic approaches to eliminate or neutralize C. difficile or
      its toxins have been proposed, including probiotic therapy with non-pathogenic
      microorganisms and several forms of immunotherapy. These alternative approaches
      are in their infancy, but initial reports appear to support efficacy against this
      stubborn infection.

PMID- 11964790
TI  - The role of interleukin-10 in critical illness.
AB  - Interleukin-10 is the most potent anti-inflammatory cytokine yet identified. It
      has multiple actions affecting the innate immune system as well as humoral and
      cellular immune responses. It occupies a pivotal role in the regulation of the
      immune response to microbial pathogens in health and disease. Knowledge gained in
      the molecular biology of IL-10 and its complex immune effects in experimental
      infection models are leading to new insights into therapeutic manipulation of IL
      10 in patients with systemic inflammatory diseases.

PMID- 11964791
TI  - Periodontal disease: bacterial virulence factors, host response and impact on
      systemic health.
AB  - Teeth are coated with a biofilm that contains periodontal pathogens. Pathogens
      express virulence factors which enable them to invade and replicate within
      epithelial cells and to invade the underlying connective tissue. This stimulates
      production of prostaglandins and cytokines that induce tissue loss. In addition,
      these bacteria have the potential to modulate the course of systemic diseases
      such as atherosclerosis and to contribute to low birthweight and preterm labor.

PMID- 11964792
TI  - Phagocytosis and killing of intracellular pathogens: interaction between
      cytokines and antibiotics.
AB  - Phagocytosis and bacterial killing are the primary functions of macrophages.
      Among the mechanisms involved in the phagocytic process, cytokines, especially
      those of T-helper 1 profile, appear to influence considerably the internalization
      and the intracellular fate of the pathogen within the macrophage. In particular,
      the evidence for a cooperation of cytokines with antibiotics in intracellular
      infection could provide new therapeutic approaches to intracellular infectious
      diseases in the future.

PMID- 11964793
TI  - Prevention of infectious diseases by neonatal and early infantile immunization:
      prospects for the new millennium.
AB  - Newborns and young infants are at increased risk of severe or prolonged
      infections. Recent advances in our understanding of the host immune response in
      this age group, coupled with the development of molecular genetic tools, have
      paved the way for a new generation of preventive vaccines.

PMID- 11964794
TI  - Prevention and treatment of perinatal HIV-1 infection in the developing world.
AB  - Measures to reduce mother-to-child transmission of HIV-1 are discussed according
      to the presumed timing of transmission. Long course antiretrovirals can
      substantially decrease intrauterine transmission. Antiretrovirals and caesarean
      section reduce vertical transmission by preventing intrapartum transmission; but
      caesarean section is unsuitable for most developing countries. Short and very
      short course antiretrovirals have an efficacy rate of about 50% in non
      breastfeeding populations compared with just under 40% at 6 months and between 23
      and 30% at 15-24 months in breastfeeding women. The latter is due to the fact
      that postnatal transmission occurs as long as breastfeeding continues.
      Breastfeeding accounts for a third to a half of overall transmission. Exclusive
      rather than mixed breastfeeding appears to diminish the risk of transmission, and
      HIV-infected women who choose to breastfeed should be advised to give breastmilk
      exclusively for a maximum of 5-6 months.

PMID- 11964795
TI  - Improving the outcome of septic shock in children.
AB  - Sepsis is an important cause of pediatric morbidity and mortality. Improving the
      outcome of pediatric sepsis requires diverse efforts, including prevention, early
      recognition, improvements in early management and transport, and physiology
      directed care. Awareness that septic shock represents a pathophysiologic host
      response to infection has prompted investigation of immune mediators and
      coagulation factors as potential targets for anti-sepsis therapies. Advancements
      thus far include: the potential prevention of neonatal sepsis with granulocyte
      colony-stimulating factor; recognition of clindamycin as a potential inhibitor of
      endotoxin release; improved outcome from meningococcal disease in children
      treated with bactericidal/permeability-increasing protein (rBPI21); and improved
      outcome from sepsis in premature infants treated with pentoxifylline. Further
      randomized controlled studies of immunomodulatory agents are indicated and a few
      are in progress. Current studies on genetic propensities in cytokine and
      coagulation protein expression may explain variability in patient outcomes and
      eventually lead to genomics-based therapeutics.

PMID- 11964796
TI  - Central nervous system infections in the tropics: diagnosis, treatment and
      prevention.
AB  - The present review is a brief discussion of some of the important new
      developments that have been reported relating to bacterial and viral infections
      of the central nervous system. For many of these conditions, certain issues
      remain unresolved, including what is the best diagnostic approach, what is the
      optimum treatment and how best to prevent such conditions. The development of
      improved surveillance, more effective vaccines and a greater understanding of the
      pathophysiology of these diseases all offer great potential benefits. The hope is
      that these advances, when they come, will be affordable to those who need them
      most.

PMID- 11964797
TI  - Emerging infectious diseases in the 21st century.
AB  - The emergence of novel infectious diseases, and the re-emergence of others, is
      not new. The global ecosystem is constantly changing, influencing the micro- and
      macroenvironments in which humans and their microbial companions reside and
      interact. Sometimes the environmental circumstances favour the pathogen and there
      is an unexpected increase in disease activity or emergence of a new infection.
      Alternatively, pathogenicity factors are acquired by the microbe, allowing new
      diseases to emerge or old diseases to increase in importance. The forces that
      drive the emergence, submergence and re-emergence of infectious diseases are
      varied, but the influence that humans have on the global ecosystem is often of
      central importance. This review considers infections that are of particular
      emerging importance.

PMID- 11964798
TI  - What is the risk of transfusing micro-organisms during stem cell transplantation?

PMID- 11964799
TI  - Infection in the neutropenic and haematopoietic stem cell transplant recipient.
AB  - Patterns of bacterial infection have remained fairly static with Gram-positive
      bacteria predominating, although this varies between institutions and between
      patient populations. Similarly, antimicrobial resistance rates differ widely and
      reflect antibiotic use and exposure. Hence, each institution should devote
      microbiological resources to maintain surveillance and employ vigilance so that
      antimicrobial treatment protocols can be adapted to meet any new challenges. Most
      changes are being seen in the diagnosis of fungal infections, particularly
      aspergillosis, and the way in which it is being incorporated into treatment
      strategies.

PMID- 11964800
TI  - Infections in solid organ transplant recipients.
AB  - Studies published within the past year have highlighted the potential morbidity
      associated with polyomaviruses and novel herpesviruses (e.g. human herpesvirus-6,
      7 and -8). Although antiviral therapy has not been shown to be effective for
      polyomaviruses, attempts at management of human herpesvirus-6 and -8 infections
      with antiviral agents appear anecdotally promising. Bacterial infections remain
      the most frequently occurring infections in transplant recipients, and the
      challenges that face the transplant care providers pertain to a striking rise in
      antimicrobial resistance among these pathogens. Effective prophylaxis and
      management of invasive mould infections continue to be the focus of clinical
      studies, but an optimal approach remains elusive.

PMID- 11964801
TI  - Infection in patients with primary immunodeficiency disorders.
AB  - Recent advances in the understanding of the molecular basis of primary
      immunodeficiency disorders are reviewed, with particular emphasis on how these
      provide insights to the normal host's handling of particular microbes. Also
      reviewed are a number of reports on series of patients with these disorders,
      documenting the incidence and nature of the infective complications that occur
      and the effectiveness of treatment strategies.

PMID- 11964802
TI  - Molecular methods in the diagnosis of infections in the immunocompromised host.
AB  - Despite recent developments, infection remains a major obstacle to a successful
      outcome in transplantation. Molecular methods have allowed for earlier diagnosis
      and have proven to be powerful tools for analysing the epidemiology of infectious
      diseases. More recently, some of these molecular methods have been
      commercialized, enabling standardized diagnostic techniques to be used in
      multicentre trials.

PMID- 11964803
TI  - Unusual infections and novel therapy in the immunocompromised host.
AB  - New methods of identification have led to an ever-increasing number of unusual
      pathogens causing infection in the immunocompromised host. Reports of
      antimicrobial-resistant organisms in this group of patients are also increasing,
      with the result that new treatments must be sought urgently. New agents and new
      strategies for the development of antimicrobial agents are critical for future
      progress in the treatment of resistant organisms.

PMID- 11964804
TI  - Antibiotic cycling: what goes around comes around.

PMID- 11964805
TI  - Geography is destiny: global nosocomial infection control.
AB  - The global nature of the emergence and spread of multiresistant bacteria has
      resulted in a slow response from governmental bodies, but surveillance networks
      are being set up and there is evidence, cited in this review, of an element of
      cooperation among professional bodies. Most developed and many developing
      countries have recognized the need for nosocomial infection control.

PMID- 11964806
TI  - Nosocomial pneumonia: epidemiology, pathogenesis, diagnosis, treatment and
      prevention.
AB  - Nosocomial pneumonia is the second most common nosocomial infection and the
      leading cause of death from hospital-acquired infection. Supine body position in
      mechanically ventilated patients, and cardiopulmonary resuscitation and
      continuous sedation are significant risk factors for developing nosocomial
      pneumonia. During the past 2 years some new therapeutic approaches for nosocomial
      pneumonia and modifications to established therapies have been described, such as
      optimal pharmacodynamic evaluations, monotherapy versus combination therapy,
      computer-assisted management programmes and antibiotic rotations.

PMID- 11964807
TI  - Nosocomial legionellosis.
AB  - Numerous reports of endemic legionellosis have been published within the past
      year. The scope has been expanded to longterm care facilities, nursing homes,
      rehabilitation centers, and pediatric hospitals. The institutional water supply
      has been the source in all reports and aspiration was explicitly linked as the
      mode of transmission in several reports. Discovery of a single case should not be
      considered as an isolated sporadic event, but instead indicative of unrecognized
      cases within that hospital. Copper-silver ionization has displaced
      hyperchlorination as the longterm disinfection modality of choice. Guidelines
      mandating the use of routine environmental cultures in hospital water supplies
      have been implemented in several American states and European countries.

PMID- 11964808
TI  - Biomaterials to prevent nosocomial infections: is silver the gold standard?
AB  - Although many antimicrobial biomaterials have shown promising activity in vitro,
      few anti-infective prosthetic devices manufactured from these materials have yet
      achieved any degree of success in clinical trials. Controversy surrounds the
      exploitation of antibiotics in these materials and the microbiological methods
      that have been used in the clinical trials on the devices.

PMID- 11964810
TI  - Letter from Nepalgunj.

PMID- 11964809
TI  - Disinfectants that do.
AB  - Biocides are helpful in different healthcare settings to reduce or eradicate
      harmful pathogens on the skin, medical devices, and in the environment. This
      article reviews recent advances in hand hygiene, instrument sterilization,
      decolonization with mupirocin, and the challenges posed by environmental
      contamination, and prion disease. Do biocides induce resistance?

PMID- 11964811
TI  - Malaria research: host-parasite interactions and new developments in
      chemotherapy, immunology and vaccinology.
AB  - Malaria remains the major parasitic disease, with 300-500 million new infections
      each year. This survey covers recent advances in the field of parasite-host
      interactions, focusing on Plasmodium falciparum, the most virulent of the human
      parasites. Rapid progress in genomic research is creating a basis for the
      development of new drugs and vaccines. Identification of drug-resistance
      mutations facilitates evaluation of improved drug policies, and attempts are
      being made to develop new compounds that inhibit metabolic pathways that are
      specific to the parasite. Cytoadherence of parasitized erythrocytes to
      microvascular endothelium is responsible for the sequestration of parasites,
      causing pathology and severe disease. Newly identified molecular fine structures
      that mediate cytoadherence may provide new targets for specific therapies.
      Humoral and cell-mediated immunity induced by the parasite may be protective, but
      may also be harmful by generating imbalance in cytokine responses. Efforts are
      made to determine the pathways that give rise to protection, with vaccination
      being the principal goal for achieving malaria control. Different vaccine
      constructs are being evaluated in preclinical and clinical trials, including
      modified viral vectors, synthetic peptides, DNA and new adjuvants.

PMID- 11964812
TI  - Developments in schistosomiasis research and management.
AB  - Schistosomiasis is a worldwide problem because it is so widely distributed, and
      few places on earth are now too remote. Some of the most important new research
      examines how parasite and host biology are integrated, how any level of infection
      contributes to the overall burden of disease, and the long-term and short-term
      outcomes of control programs.

PMID- 11964813
TI  - Recent developments in amoebiasis research.
AB  - Invasive amoebiasis, the infection of humans by Entamoeba histolytica associated
      with dysentery and liver abscess, is still a major cause of morbidity and
      mortality in developing countries. This review attempts to reduce the gap between
      the overwhelming amount of information coming recently from laboratory research
      and the sparse contributions resulting from clinical and epidemiological
      investigations of the second parasitic cause of death resulting from a protozoan
      parasite.

PMID- 11964814
TI  - Human onchocerciasis: the essential partnership between research and disease
      control efforts.
AB  - Twenty years ago onchocerciasis was a disease generally ignored by the medical
      world, except by those who actually worked with the affected people in Africa and
      Latin America. Now, largely as a result of the success of mass vector control and
      drug treatment programs, this is a disease management model for developing
      countries. The recent literature on onchocerciasis has, not surprisingly, mainly
      focused on various aspects of control. Investigation into the more basic
      questions is needed to ensure continued effective disease control. The present
      mass drug control program is based on a single pharmaceutical, ivermectin
      (Mectizan), which acts almost exclusively on the microfilarial stage of the
      infection. Efforts are being made to identify other useful drugs; however, no
      major candidates have yet appeared. The identification of potential biochemical
      targets for anti-filarial compounds through a better understanding of the
      biochemistry of these worms is being pursued. The Onchocerca volvulus
      endosymbiont Wolbachia may provide a target for therapeutic intervention. An
      improved understanding of the genomics of O. volvulus has made possible the
      identification of strain differences in the parasites, and an appreciation of the
      relevance of these strain differences to the clinical disease, onchocerciasis.
      There is a need for a better understanding of the clinical disease, and the
      various pathogenic mechanisms that underly the different syndromes. It is
      particularly important to understand the pathological basis and mechanisms
      underlying the adverse responses that can occur with chemotherapy. Present
      control programs now need to be carefully monitored for effectiveness using new
      assessment tools, such as antigen assays and the identification of organisms in
      pools of vectors. Current efforts to control onchocerciasis must be coordinated
      with new chemotherapy-based control programs for other worm diseases that are
      emerging. The results of laboratory studies are increasingly being applied to
      improve the effectiveness of field-based control programs and their assessment.
      Such research is essential for progress towards the goals of controlling and
      eliminating onchocerciasis.

PMID- 11964815
TI  - Helminths.
AB  - Helminths affect more than one quarter of the world's population, contributing
      significantly to socioeconomic problems in developing countries. Control is
      heavily dependent on chemotherapy, which can be cost-effectively targeted to
      school-age children, in whom combined drug treatments work well. Drug resistance,
      however, is a constant threat. Human behaviour significantly influences
      transmission. New infections or foci are frequently reported and tourism exposes
      non-endemic individuals to serious risks. Infection and pathology are strongly
      influenced by genetic factors, which are now being defined. Immune responses
      contribute to both protection and pathology. Clarification of these responses is
      providing opportunities for vaccination and for the modulation of
      immunopathology.

PMID- 11964817
TI  - Gastrointestinal infections: you can hide but you still have to run.

PMID- 11964816
TI  - Dengue haemorrhagic fever: questions of pathogenesis.
AB  - The year under review has seen a remarkable proliferation of papers on dengue.
      Four prospective studies have been carried out across the dengue belt, many
      groups have been pushing at the question of pathogenesis of dengue haemorrhagic
      fever, and a breakthrough has been achieved in the development of a mouse model
      for human dengue haemorrhagic fever.

PMID- 11964818
TI  - Genetic variations of hepatitis B virus.
AB  - The emergence of hepatitis B virus genetic variants occurs under the influence of
      host immunity, immunization, the use of immune globulin or antiviral
      chemotherapy. Most of these are probably the result of the 'immune escape'
      phenomenon. Some variants, in particular those in the precore and core promoter
      regions, have been associated with disease severity and progression. Surface
      antigen variants have implications for the accuracy of laboratory diagnosis and
      may reduce the effectiveness of vaccination. Polymerase variants are selected as
      a result of the use of antiviral chemotherapeutic agents. It is important to
      monitor the occurrence of these variants.

PMID- 11964819
TI  - The prevention and management of viral hepatitis.
AB  - In this review we will discuss advances in the primary and secondary prevention
      of viral hepatitis and the treatment for chronic viral hepatitis.

PMID- 11964820
TI  - Rotavirus vaccines.
AB  - The past few years have seen important developments in understanding the
      epidemiological and virological characteristics of rotaviruses, and rapid
      progress has been made in rotavirus vaccine development, but further challenges
      remain before a vaccine is introduced into widespread use. The licensure of the
      first rotavirus vaccine, a tetravalent rhesus-based rotavirus vaccine, in the
      United States in 1998, marked a significant advance in preventing the morbidity
      associated with rotavirus diarrhea. The association between the tetravalent
      rhesus-based rotavirus vaccine and intussusception has created significant
      hurdles as well as new opportunities to study the pathogenesis of rotavirus and
      rotavirus vaccine infection. Several other rotavirus vaccine candidates are in
      late stages of development, and results from trials have been encouraging.

PMID- 11964821
TI  - Bacteria and inflammatory bowel disease.
AB  - The cause of inflammatory bowel disease is unknown, but both environmental and
      genetic factors are implicated. This review presents evidence from recent studies
      involving both animal models and inflammatory bowel disease patients, which
      supports a role for bacteria in the aetiology and pathogenesis of Crohn's disease
      and ulcerative colitis.

PMID- 11964822
TI  - Enteropathogenic and enterohaemorrhagic Escherichia coli and diarrhoea.
AB  - Enteropathogenic and enterohaemorrhagic Escherichia coli are important causes of
      bacterial gastroenteritis with the potential for progression to more serious
      syndromes, especially in the case of enterohaemorrhagic E. coli. Consequently,
      recent developments in molecular epidemiology and treatment regimens have focused
      on enterohaemorrhagic E. coli, while the similar initial pathogenic mechanisms of
      both enterohaemorrhagic and enteropathogenic E. coli continue to be investigated
      in detail. The carriage of most E. coli virulence determinants on pathogenicity
      islands, plasmids or phages allows the rapid evolution of these pathotypes, which
      need to be monitored closely.

PMID- 11964823
TI  - Molecular mechanisms of Salmonella pathogenesis.
AB  - The success of a pathogen depends on its capacity to enter a host, circumvent
      host defense barriers and establish infection. The Gram-negative bacterium
      Salmonella enterica has evolved different strategies to subvert normal host
      cellular functions, which allow it to enter into and proliferate within host
      cells.

PMID- 11964824
TI  - Role of the neuroendocrine system in pathogenesis of gastroenteritis.
AB  - The concept of neuroendocrine modulation of infectious gastroenteritis adds
      another dimension to the pathophysiology of diarrhoeal diseases. Furthermore it
      opens up new avenues for therapeutic intervention. Until now, most interest has
      been directed at enterotoxin-producing bacteria, notably Vibrio cholerae and the
      enterotoxigenic Escherichia coli. However, more recently neuroendocrine
      recruitment has been implicated by other pathogens. The roles of vasoactive
      intestinal peptide, 5-hydroxytryptamine, tachykinins, nitric oxide and opioids
      are explored in this review. In addition new insights in the contradictory
      galanin story are discussed.

PMID- 11964825
TI  - Current and future approaches to antifungal therapy.

PMID- 11964826
TI  - The evolving relationship between Chlamydia pneumoniae and atherosclerosis.
AB  - A body of evidence supports an association between Chlamydia pneumoniae and
      atherosclerosis. Recent prospective, seroepidemiologic studies have refined
      estimations of relative risk. Advances in diagnostic testing with the polymerase
      chain reaction have created a potential opportunity to screen for infected
      individuals. New insights into the pathogenesis of infection with C. pneumoniae
      have been reported, many of which are relevant to the development of
      atherosclerotic plaque. Clinical trials have now been initiated and should
      provide guidance as to the utility of antibiotics in the treatment or prevention
      of coronary artery disease.

PMID- 11964827
TI  - New Gram-positive agents in nosocomial infection.
AB  - Multidrug-resistant Gram-positive pathogens such as vancomycin-resistant
      enterococci, methicillin-resistant Staphylococcus aureus, and methicillin
      resistant coagulase-negative staphylococci account for a significant number of
      nosocomial infections, and new options for therapy have been lacking. During the
      past year, two agents have been released that have activity against these
      organisms: quinupristin/dalfopristin and linezolid. Although neither agent is a
      panacea, these recently released agents offer new options for therapy.

PMID- 11964828
TI  - Sequential antibiotic therapy.
AB  - Antimicrobials are an important source of hospital expenditure. Traditionally,
      severe bacterial infections have been treated initially with intravenous
      antibiotics, followed by physician-directed switch to oral therapy. Unfortunately
      this approach results in unnecessary prolongation of intravenous treatment, with
      all its inherent disadvantages. Sequential antibiotic therapy, however, ensures
      an early switch to the oral route when the patient is clinically stable. This
      increasingly employed strategy is safe and results in improved quality and cost
      effectiveness of health care. To ensure timely and appropriate switch, such
      programmes need to be underpinned by clear guidelines and supported by a
      multidisciplinary team. In the future, key questions, such as what is the optimal
      time of switch for specific infections, and can conditions such as osteomyelitis
      and endocarditis be efficaciously treated with oral therapy, need to be answered.
      Only then will clinicians be able to practise evidence-based infection management
      incorporating sequential antimicrobial therapy.

PMID- 11964829
TI  - Approaches to antifungal therapy in the intensive care unit.
AB  - The risk of fungal infection is increasing in intensive care unit patients and
      the spectrum of pathogens is changing. A number of new antifungal agents are
      becoming available, but their use in critically ill patients has not been
      assessed in randomized controlled trials. Furthermore, distinguishing
      colonization from infection is problematic in intensive care unit patients.
      Clinicians who are involved in the management of intensive care unit patients
      must remain vigilant and devise a risk-based antifungal strategy that is based on
      local experience and susceptibility patterns.

PMID- 11964830
TI  - The changing spectrum of candidemia in oncology patients: therapeutic
      implications.
AB  - Infections caused by Candida spp. are frequent and serious in oncology patients.
      Over the past decade, the introduction of azole antifungals as prophylactic
      agents, and other factors have caused a shift in the species of Candida that
      cause infection. During the period under review (June 1999 to June 2000), several
      studies have been reported that confirm the impact of antifungal prophylaxis and
      the emergence of non-albicans Candida spp. as pathogens. Moreover, laboratory
      studies to determine the antifungal susceptibilities and virulence properties of
      non-albicans Candida spp. have enabled the formation of microbe-specific
      management strategies. More of these studies will be necessary as we enter an age
      in which multiple antifungal compounds will become available for clinical use.

PMID- 11964831
TI  - Combination antiviral therapy: but which combination, and why?

PMID- 11964832
TI  - The potential use of anti-enteroviral drugs in the immunocompromised.
AB  - Therapy for enteroviral infection is now a reality, and one compound, pleconaril,
      has been successfully used in a number of clinical trials, with others likely to
      follow over the next few years. Antibody-deficient patients are particularly
      prone to chronic enteroviral infection, and have proved to be a useful model in
      which to examine the efficacy of new drugs. Apart from polioviruses, immunization
      and immunotherapy to prevent and treat infection is probably impracticable
      because so many different strains are involved. Ultimately, combination drug
      therapy will probably be the best strategy to treat chronic infection.

PMID- 11964833
TI  - The role of observational studies in assessing the impact of antiviral therapies.
AB  - During the past year many observational studies have reported on the impact of
      highly active antiretroviral therapy on their patient populations. Care should be
      taken when interpreting these findings because of possible biases due to
      reporting delay and loss to follow-up. The results are very encouraging, however,
      suggesting dramatic reductions in the incidence of AIDS and death, and resulting
      hospitalizations.

PMID- 11964834
TI  - When can cytomegalovirus prophylaxis and maintenance therapy be stopped in HIV
      disease?
AB  - Highly active antiretroviral therapy (HAART) can restore immune responses to a
      variety of pathogens, including cytomegalovirus. Following successful HAART,
      prophylaxis and maintenance therapy for cytomegalovirus can safely be stopped in
      selected patients. However, the risk of cytomegalovirus disease progression
      recurs if HAART fails, and so these patients require careful monitoring.

PMID- 11964835
TI  - Mechanisms of hepatitis B virus escape after immunoglobulin therapy.
AB  - Passive immunoprophylaxis with hepatitis B immunoglobulin is used to reduce the
      risk of infection of grafts after liver transplantation and also to protect
      newborn children of hepatitis B virus-infected mothers. The use of hepatitis B
      immunoglobulin is associated with the emergence of variant viruses or escape
      mutants that have specific amino acid substitutions in immunodominant epitopes.
      Under these circumstances, high serum titres of the virus may be observed in the
      context of apparently protective levels of antibody to hepatitis B surface
      antigen. The potential impact of hepatitis B surface antigen variation on
      vaccination strategies remains a contentious issue. As the burden of hepatitis B
      virus is dramatically reduced by major vaccination programmes, a greater
      proportion of carriers will demonstrate hepatitis B surface antigen variation
      from wild-type. The degree of protection afforded by current vaccines from
      subsequent infection by variants of the virus is unknown. Concern is raised over
      the potential impact of hepatitis B surface antigen variation on hepatitis B
      virus polymerase inhibitor susceptibility, and the reduced sensitivity of current
      antigen assays for detection of hepatitis B surface antigen variants.

PMID- 11964836
TI  - Problems for the chemotherapy of human African trypanosomiasis.
AB  - Problems associated with the current therapies of sleeping sickness include
      toxicity, resistance and a lack of a guaranteed supply. However, no new
      formulations are close to gaining a licence for clinical use and relatively few
      compounds have been shown to be effective in experimental systems. Many
      potentially good biochemical targets for drugs have been identified. Some of
      these have been validated and lead compounds have been developed. However, the
      biology of trypanosomes means that various pharmacological demands must be met in
      developing new trypanocides for clinical use. Foremost among these problems is
      the blood-brain barrier, across which trypanocides must cross to reach parasites
      in the cerebrospinal fluid.The principal problem, however, relates not to
      biological difficulties, which are technically surmountable, but to economics.
      Put simply, most representatives of the pharmaceutical industry believe that
      selling drugs to the victims of sleeping sickness will not yield sufficient
      income to justify expenses needed for the development of novel reagents. Only
      when this economic barrier can be lowered will new drugs emerge for use against
      sleeping sickness.

PMID- 11964837
TI  - Changing ideas on chloroquine in Plasmodium falciparum.
AB  - For 40 years scientists have hotly debated the questions of how chloroquine kills
      malarial parasites and how resistance to this once first-line antimalarial drug
      has evolved. While an end to these debates is not in sight, as a result of the
      complexity of the subject, new findings have come forward that give the
      discussion a new direction. In this paper we will summarize current knowledge on
      chloroquine's antimalarial mode of action and the genesis of the resistant
      phenotype in the human malarial parasite Plasmodium falciparum, with special
      emphasis on the most recent developments in this field.

PMID- 11964838
TI  - Praziquantel: is there real resistance and are there alternatives?
AB  - The low cure rates obtained with praziquantel in a Senegalese focus of
      schistosomiasis can best be interpreted on the basis of epidemiological factors,
      and are unlikely to be connected with any drug resistance in the parasite.
      Schistosome isolates obtained in Egypt from uncured patients present evidence of
      lower susceptibility to the drug, albeit to a rather limited extent. Similarly,
      laboratory schistosomes subjected to repeated passages under drug pressure are
      partly insensitive to the drug. Oxamniquine is at present the only available
      alternative to praziquantel. Research and development of new antischistosomal
      drugs is urgently needed.

PMID- 11964839
TI  - Bacterial shock: clinical definitions, clinical trials and the dynamics of the
      host response.

PMID- 11964840
TI  - Mechanisms of chronic enteroviral persistence in tissue.
AB  - Although the association remains controversial, enteroviruses have been
      implicated in the aetiology of several chronic diseases in humans. Investigations
      in vitro lead to better understanding of virus-cell interactions, and improve our
      knowledge of the molecular factors that are involved in the establishment and
      maintenance of these infections. Recent findings suggest that the most important
      factor in the establishment of a persistent infection is receptor usage. Studies
      of the mechanisms that are at work in these in-vitro models of viral infection
      have shown that there is frequently a co-evolution of mutant cells with higher
      resistance to viral infection and of virus variants with increased virulence
      (i.e. variants with the ability to utilize other cell-surface molecules as
      receptors).

PMID- 11964841
TI  - Roles of prostaglandins and leukotrienes in acute inflammation caused by
      bacterial infection.
AB  - Prostanoids, including prostaglandins and thromboxanes, are generated by the
      phospholipase A2/cyclooxygenase pathway, and leukotrienes are generated by the 5
      lipoxygenase pathway from arachidonic acid. At physiological concentrations,
      vasodilator prostaglandins enhance the vascular permeability effects of histamine
      and bradykinin, and leukotrienes are important mediators of leukocyte
      accumulation during acute inflammation. On the other hand, prostaglandin
      metabolites such as cyclopentenone prostaglandins contribute to the resolution of
      acute inflammation through inhibition of nuclear factor-kappaB activation. Thus,
      arachidonic acid oxygenation products mediate diverse effects that induce and
      resolve acute inflammation caused by bacterial infection.

PMID- 11964842
TI  - The protective role of interleukin-18 in Salmonella infection.
AB  - Since its derivation, much has been learned about the proinflammatory inducing
      cytokine interleukin-18, and its role in resolving infectious diseases. Studies
      to date that examined interleukin-18 have shown that endogenously induced
      interleukin-18 plays an important protective role in some viral and bacterial
      infections. However, interleukin-18 has a limited role in protective immunity to
      Salmonella infections, and is secondary to the protective role of interleukin-12.
      This lack of sensitivity to interleukin-18 may be in part related to the
      dependence on interleukin-12 for interleukin-18 receptor expression and to the
      nanomolar concentrations that are required. Nonetheless, an understanding of how
      some pathogens have evolved to circumvent interleukin-18 and of how interleukin
      18 can be effectively induced are essential to our ability to develop better
      vaccines against enteric pathogens.

PMID- 11964843
TI  - The role of the neutrophil and phagocytosis in infection caused by Helicobacter
      pylori.
AB  - Recent advances in our understanding of Helicobacter pylori-phagocyte
      interactions indicate that these organisms actively modulate phagocyte function
      in order to retard phagocytosis, while simultaneously inducing a strong
      respiratory burst. The central players in this dynamic include H. pylori
      neutrophil activating protein and factors that are associated with the cag
      pathogenicity island type IV secretion apparatus. Additionally, catalase, alkyl
      hydroperoxide reductase, and factors that are unique to type I strains allow
      bacteria to resist phagocytic killing.

PMID- 11964844
TI  - Cytokines and chemokines in the immune response to hepatitis C infection.
AB  - Over 170 million people are infected with the hepatitis C virus worldwide,
      resulting in a large disease burden and significant mortality. Hepatitis C virus
      is rarely cleared in the acute phase of the infection and most patients become
      chronically infected; a proportion of these patients develop progressive liver
      disease and fibrosis. The outcome of infection depends on the immune responses of
      both the innate and cognate immune systems, and these in turn are orchestrated by
      networks of cytokines and chemokines. There is evidence that a vigorous type 1
      immune response to viral proteins is required for viral elimination, and the
      recruitment of such effector cells to the liver is dependent on the local
      activity of specific inducible chemokines. Multiple factors determine the ability
      of the hepatitis C virus to survive host immune responses, including an ability
      to alter the cytokine profile secreted by T cells and to cause resistance to the
      effects of antiviral cytokines such as interferon. In the present review, we
      briefly cover the important advances made in this area over the past 12 months.

PMID- 11964845
TI  - The role of C-reactive protein in the resolution of bacterial infection.
AB  - C-reactive protein is an acute phase protein in man and an important component of
      the innate immune system. C-reactive protein activates the classical pathway of
      complement, which is one of its main mechanisms in providing host defense. It has
      recently been recognized that C-reactive protein interacts with the cells of the
      immune system by binding to Fc gamma receptors. It may thus bridge the gap
      between innate and adaptive immunity and provide an early, effective
      antibacterial response. Furthermore, as it protects against the damaging
      inflammatory response to lipopolysaccharide and cytokines, it may prevent the
      lethal side-effects of bacterial products. The recent identification of the
      interaction of C-reactive protein with Fc gamma receptors will lead to an
      enhanced understanding of C-reactive protein and its role in both the innate and
      acquired immune systems.

PMID- 11964846
TI  - The role of colostral antibodies in prevention of microbial infections.
AB  - Mammalian colostrum offers passive protection to the newborn against a variety of
      microbial pathogens, in the form of specific immunoglobulin A, G and M
      antibodies. Sharing maternal immunological memory is in many cases vital for the
      infant, but may have disastrous consequences, such as involuntary transfer of
      disease and disturbance of the developing immune system. In most published
      studies, immune milk preparations are reported to be effective in the prevention
      of various gastroenteric infections, but not in the treatment of an established
      infection.

PMID- 11964847
TI  - Drug therapy in children: still more art than science.

PMID- 11964848
TI  - Nosocomial infections in the neonatal intensive care unit.
AB  - Nosocomial infections are significant causes of morbidity and mortality in
      patients who require newborn intensive care. The most common bacterial pathogens
      are Gram-positive bacteria, including Staphylococcus epidermidis, Staphylococcus
      aureus, and Enterococcus species. Gram-negative enteric bacilli and Gram-negative
      environmental bacteria are involved in outbreaks and occasional cases of
      nosocomial infection. The incidence of fungal infection has increased over the
      past 10 years; fungemia is the most commonly recognized infection. Surveillance
      for nosocomial infection is essential to identify outbreaks and detect
      unsuspected reservoirs of pathogens. A variety of molecular techniques can be
      used to determine the genetic relatedness of pathogens. Prevention of infection
      requires the identification of contaminated equipment, education regarding
      infection control methods including hand washing, and the judicious use of
      antimicrobial agents.

PMID- 11964849
TI  - Urinary tract infection: new perspectives on a common disease.
AB  - Urinary tract infection is an important cause of morbidity in children, and
      affects up to 10% of the childhood population. Recent information suggests that
      the long-term outcome for children with urinary tract infection is much better
      than previously believed, with causal links to end-stage renal disease and
      hypertension not demonstrated despite 20-year cohort studies. Improvements in the
      use of dipstick and clinical features as diagnostic tools have occurred, but
      culture is still needed if the diagnosis of urinary tract infection is to be
      definitively established. Interventions to prevent recurrent urinary tract
      infection, particularly low-dose, long-term antimicrobial agents may not be
      effective and placebo-controlled trials are now required.

PMID- 11964850
TI  - The role of Helicobacter pylori in paediatrics.
AB  - Helicobacter pylori is a bacterium that colonizes the human stomach, especially
      during childhood. Although it has been studied intensively during the past
      decade, many controversies still exist on many important issues, including the
      clinical relevance of virulence factors, indications for treatment, recommended
      procedures for diagnosis and the typical symptom profile, among others. The lack
      of double-blind, placebo-controlled studies in children illustrates the paucity
      of hard scientific data, and is the major reason for differences in opinion.
      Therefore, the present review of literature published during the past 2 years
      raises many questions.

PMID- 11964851
TI  - Management of respiratory syncytial virus infection.
AB  - Although bronchiolitis is the most common viral lower respiratory tract infection
      in infancy and childhood, and the virus responsible (respiratory syncytial virus)
      was discovered half a century ago, there is no effective treatment available. The
      antiviral agent ribavirin has not lived up to expectations and should be reserved
      for selected cases. Corticosteroids have not been shown to be effective in
      individual trials, although a recent meta-analysis suggested a mild beneficial
      short-term effect. Bronchodilators can be used on a trial-and-error basis.
      Prophylaxis with intravenous immunoglobulins enriched for anti-respiratory
      syncytial virus antibodies or humanized monoclonal antibodies can reduce the
      rates of related hospitalization by 50% when used in high-risk patients. However,
      logistical problems with the administration of intravenous immunoglobulins and
      the cost of both products preclude their widespread use.

PMID- 11964852
TI  - Pertussis: an old disease that is still with us.
AB  - Our knowledge of pathogenesis, clinical presentation and prevention of pertussis
      has improved substantially over recent years. We now better understand the
      function of long-known virulence factors for Bordetella pertussis, and genome
      sequencing has identified a multitude of new proteins; their functions are yet to
      be elucidated. Furthermore, improved diagnostic tools have revealed the broad
      spectrum of disease, and new insights into the host's immune response have been
      gained. Finally, the development, evaluation, licensing and implementation of
      several new acellular pertussis vaccines with high acceptance have changed the
      epidemiology of pertussis in many countries (i.e. a shift towards an increasing
      burden of disease in adolescent persons and adults). These developments are
      likely to have great impact on the daily practice not only of paediatricians, but
      also of general practitioners, internists, gynaecologists and many other
      specialists in adolescent and adult medicine. The present review provides an
      update on recent progress.

PMID- 11964853
TI  - Current approaches to otitis media.
AB  - Acute otitis media is the most commonly diagnosed illness in children, and is one
      of the most common reasons for antibiotic prescription. In many countries,
      antibiotic resistance is increasing among the bacteria that are implicated in
      acute otitis media, particularly Streptococcus pneumoniae. This evolution should
      stimulate changes in the management of acute otitis media, particularly the
      following: improvement in diagnostic accuracy; reduction in antibiotic use;
      selection of the most appropriate drugs at the appropriate dosage; reduction in
      duration of treatment, when possible; and implementation of new vaccines.

PMID- 11964854
TI  - Fifth (human parvovirus) and sixth (herpesvirus 6) diseases.
AB  - Fifth (erythema infectiosum) and sixth (roseola infantum) diseases are common
      rash illnesses of childhood that have long been recognized in clinical medicine.
      The discovery of the viruses that cause these illnesses has revealed
      relationships with other syndromes. Primary infection with the agent of erythema
      infectiosum, human parvovirus B19, is associated with transient aplastic crisis
      in hemolytic anemia, arthropathy in adults, chronic anemia in immunocompromised
      patients, and nonimmune fetal hydrops in pregnant women. The only documented
      illness associated with primary infection with human herpesvirus 6 is roseola or
      exanthema subitum in young children. However, reactivated infections in adults
      and immunocompromised patients may be associated with serious illness such as
      encephalitis/encephalopathy, and bone marrow suppression leading to transplant
      failure or graft-versus-host disease. Diagnostic studies for both viruses have
      been limited, although reliable serologic tests for human parvovirus B19 have
      recently become available. Diagnosis of human herpesvirus 6 remains problematic,
      because current tests cannot differentiate primary from reactivated disease. This
      is more of an issue for the putative relationship of these viruses to more
      chronic conditions, such as rheumatologic disease for human parvovirus B19 and
      multiple sclerosis for human herpesvirus 6. The relationship between the viruses
      and these conditions remains controversial, and better diagnostic tests and
      further information on viral pathogenesis for both viruses are required in order
      to make a reliable judgment in this regard.

PMID- 11964855
TI  - Recent developments in Kawasaki disease.
AB  - Kawasaki disease is now being recognized as the leading cause of acquired heart
      disease in children in North America and Japan. This review discusses the recent
      developments and controversies in Kawasaki disease. Increasing evidence has
      supported an infectious etiology for Kawasaki disease; however, the debate
      continues as to whether the inflammatory response results from a conventional
      antigen or a superantigen. Recent immunohistochemistry findings suggest many
      vascular growth factors then play a role in the formation of the coronary artery
      lesions. Many studies have focused on the identification and therapy for patients
      resistant to conventional therapy, as well as the long-term prognosis of Kawasaki
      disease survivors. The recent advances in Kawasaki disease are helping to provide
      some clues in the etiology, pathogenesis and therapy for Kawasaki disease.

PMID- 11964856
TI  - Pseudomonas aeruginosa infections in cancer patients: have they gone away?
AB  - Pseudomonas aeruginosa infection continues to be a threat to cancer patients,
      especially if they are neutropenic. As many as 50% of infections are community
      acquired. Prompt, effective therapy results in cures in about 80% of patients,
      although the presence of shock or pneumonia indicates a poor prognosis.
      Antibiotic resistance is an increasing problem.

PMID- 11964857
TI  - Infectious complications of purine analog therapy.
AB  - Patients with lymphoid malignancies such as chronic lymphocytic leukemia,
      particularly those who receive the newer purine analogs, are at increased risk
      for infectious morbidity and mortality. Defects in cell-mediated immunity appear
      to be a major predisposing factor in these patients. An expanding spectrum of
      pathogens associated with lymphocytopenia and depletion of CD4 has been described
      in the setting of therapy with purine analogs. During the past 2 years new
      knowledge about the immunosuppression related to that treatment has continued to
      accumulate.

PMID- 11964858
TI  - Risk assessment and risk-based therapeutic strategies in febrile neutropenia.
AB  - Different approaches have developed over time regarding the empirical
      antimicrobial therapy of fever in neutropenic patients. The use of intravenous
      antibiotics remains the standard approach. Clinical criteria and 'low-risk'
      prediction rules have been developed that help select patients in whom oral
      therapy is well tolerated and who may be eligible for outpatient management.
      Comorbidity and clinical status at presentation remain important criteria in the
      risk-assessment process. Outpatient management requires additional assessment of
      non-medical criteria. Patients without documented infection and who have
      responded to initial therapy may benefit from simplified therapy such as a switch
      to oral drugs and/or outpatient management. Discontinuation of therapy may be
      considered in selected cases. Risk assessment in neutropenic patients with
      persistent unexplained fever is challenging. Available data suggest that
      broadening of the antibacterial coverage is of limited value. Instead, definition
      of the risk of fungal infection by using clinical criteria, imaging and
      laboratory studies, as well as the identification of those patients likely to
      benefit from antifungal therapy, appear to be of critical importance.

PMID- 11964859
TI  - Antifungal prophylaxis in hematopoietic stem cell transplant recipients.
AB  - Infections remain a major complication of hematopoietic stem cell
      transplantation, with recent trends indicating that fungal pathogens have become
      one of the most common causes of death. Attention has turned to the use of
      prophylactic antifungal medications to prevent infection with both Candida and
      Aspergillus species. Recent studies, which are reviewed within, indicate success
      in preventing infections caused by azole-susceptible Candida species, accompanied
      by improved transplant-related mortality rates in high-risk patients. Further
      studies are necessary to develop strategies to prevent infection with Aspergillus
      species.

PMID- 11964860
TI  - Infection control issues after bone marrow transplantation.
AB  - Bone marrow transplant recipients are at increased risk of a variety of
      infections from endogenous and exogenous sources. Various practices, including
      the use of prophylactic agents and a controlled environment are often employed in
      the name of infection control. Comparable data are lacking because of non-unified
      definitions of infection and endpoints. Antibiotic-resistant bacteria and fungi
      are being isolated more frequently as a result of selective pressure.

PMID- 11964862
TI  - Nosocomial transmission of antibiotic-resistant microorganisms.
AB  - The spread of nosocomially acquired, antibiotic-resistant microorganisms has
      grown dramatically over the past 20 years and has increasingly attracted the
      attention of academic inquiry. This article reviews recent epidemiological data
      about the trends and patterns of nosocomial transmission, presents clinical
      studies investigating mechanisms of cross-transmission, and discusses recent
      literature on preventive strategies aimed at reducing hand-carriage of antibiotic
      resistant pathogens.

PMID- 11964861
TI  - Antibiotic resistance: closing the loop.

PMID- 11964863
TI  - Diagnostic tests for healthcare epidemiology.
AB  - Diagnostic tests are important tools for surveillance in healthcare epidemiology.
      Recent studies regarding the use of diagnostic tests for detecting the following
      epidemiologically important conditions or pathogens are reviewed: vancomycin
      resistant enterococci, Legionella, influenza, ventilator-associated pneumonia,
      Clostridium difficile, bloodstream infection, and tuberculosis.

PMID- 11964864
TI  - Infection control in pediatric hospitals.
AB  - Important characteristics of hospital infection control are specific to pediatric
      facilities. For example, colonization and infection with vancomycin-resistant
      enterococci, which are widely spread in many units housing adult patients, are
      uncommon in children, especially in the neonatal intensive care unit where
      vancomycin use is heavy. Characteristics of the neonatal intensive care unit,
      such as the insulated environment and infrequent treatment with antibiotics with
      broad anaerobic activity, likely account for this finding. Artificial fingernails
      have been discovered to promote colonization with potential pathogens; their
      implication in recent nursery epidemics emphasizes the need to prohibit their use
      in this environment in particular. Finally, nosocomial viral infections occur
      with regularity in pediatric hospitals. Programs that successfully and cost
      effectively control hospital spread of respiratory syncytial virus, however,
      demonstrate that rational, multifaceted interventions can nearly eliminate
      transmission of certain viral pathogens on the pediatric wards.

PMID- 11964865
TI  - Long-term care facilities as sources of antibiotic-resistant nosocomial
      pathogens.
AB  - Long-term care facilities house individuals that have usually been transferred
      from acute-care institutions. For this reason, carriage of methicillin-resistant
      Staphylococcus aureus (MRSA), resistant Gram-negative bacilli and vancomycin
      resistant enterococci (VRE) is relatively frequent. As these patients are
      readmitted to acute-care institutions, they reintroduce these organisms into
      those settings. It is notable that studies of these resistant organisms in long
      term care facilities demonstrate little transfer between patients. Transmission
      of these bacteria and the development of infection in nursing homes are both
      uncommon events. Resources are best devoted to infection-control basics than to
      isolation of patients colonized or infected with these organisms.

PMID- 11964866
TI  - Infection control in developing countries.
AB  - Infection control activities in developing countries have increased substantially
      during the last decade, particularly in certain regions of the world. Pressure to
      improve hospital care cost-effectiveness, the emergence of highly resistant
      microorganisms, the perception of healthcare worker occupational hazards, and
      public claims for improved health assistance quality have been important factors
      responsible for this development. A major challenge for infection control
      personnel in developing countries is to sustain this development.

PMID- 11964867
TI  - Emerging viral infections.
AB  - The past decade has witnessed the emergence of several significant viral
      pathogens and the further evolution of additional viral pathogens. Transmitted by
      a variety of differing routes, these organisms have presented substantial
      intellectual challenges to medicine of the 20th and 21st centuries. As perhaps
      the benchmark pathogen of the past decade, HIV has provided medicine and society
      with a most formidable opponent, and one that has yet to be fully conquered.
      Nonetheless, a variety of additional viral pathogens have also perplexed medicine
      over the past 10-15 years.

PMID- 11964869
TI  - Cotrimoxazole prophylaxis in adults infected with HIV in low-income countries.
AB  - Two recent placebo-controlled trials of cotrimoxazole in HIV-infected adults,
      conducted by independent groups but in the same city (Abidjan, Cote d'Ivoire),
      have both shown important positive impacts. One study where cotrimoxazole or
      placebo was given to tuberculosis-HIV co-infected patients showed a significant
      reduction in mortality; the second study with a similar protocol, in HIV-infected
      patients without major co-morbidity at trial entry, showed a significant
      reduction in morbidity but no effect on mortality. These data have been
      interpreted by some as conclusive enough to recommend cotrimoxazole for all
      people with HIV/AIDS in Africa. Others have been more cautious, noting that
      Abidjan has an atypically low rate of cotrimoxazole resistance among bacterial
      pathogens, and consider more data are needed before such a sweeping policy
      decision can be made. Recent data from Senegal showed no benefit but this trial,
      like several others, was terminated prematurely because the investigators felt it
      unethical to continue after the Abidjan results were released. The situation is
      somewhat confused and confusing. This review attempts to put the current debate
      into context and to review the current position of cotrimoxazole in relation to
      other primary prophylaxis strategies in Africa.

PMID- 11964870
TI  - Recent advances in vaccines against viral haemorrhagic fevers.
AB  - Development of vaccines against viral haemorrhagic fevers is a public health
      priority. Recent advances in our knowledge of pathogenesis and of the immune
      responses elicited by these viruses emphasize the crucial role of the immune
      system in the control of infection, but also its probable involvement in
      pathogenesis. Several vaccine candidates against viral haemorrhagic fevers have
      been evaluated in animals during the past year. Together, these data suggest that
      a vaccine approach against viral haemorrhagic fevers is feasible, should induce
      well-balanced immune responses with cellular and humoral components, and should
      avoid the potential deleterious effects that are associated with such immune
      responses.

PMID- 11964871
TI  - West Nile virus in the western hemisphere.
AB  - West Nile virus first appeared in the western hemisphere in 1999 in New York.
      Genetic analysis determined that the virus was introduced from the Mediterranean
      Basin. This review discusses the establishment of West Nile virus in the naive
      environment of the northeastern USA, its ecology, epizootiology, pathology,
      prevention and prediction, as well as laboratory studies that have been conducted
      to elucidate the transmission cycle.

PMID- 11964872
TI  - Leptospirosis.
AB  - Leptospirosis is a globally important zoonotic disease that affects humans on all
      continents, in both urban and rural contexts, and in temperate and tropical
      climes. Leptospirosis is a disease of the environment; transmission depends on
      interactions between humans and mammalian reservoir hosts. A variety of
      infectious diseases that present as undifferentiated febrile syndromes, such as
      malaria, dengue and influenza, as well as viral hemorrhagic fevers can mimic
      leptospirosis. The importance of pulmonary hemorrhage as a lethal complication of
      leptospirosis has become more widely recognized. In contrast to textbook dogma,
      population-based studies indicate that there is a poor correlation between
      infecting leptospiral strain and clinical expression of disease. Genetic
      transformation of a Leptospira sp. has now been reported, which should allow for
      detailed analysis of a variety of leptospiral genes. Publication of the whole
      Leptospira genome is eagerly awaited. Following recent reports of a new, highly
      effective conjugate typhoid vaccine, new efforts to find leptospirosis vaccines
      should include the manufacture and testing of conjugate leptospiral
      lipopolysaccharide vaccines. Recent advances, particularly in epidemiology,
      molecular genetics and pathogenesis, are placing leptospirosis at the cutting
      edge of biomedical science.

PMID- 11964873
TI  - Lymphatic filariasis: new insights and prospects for control.
AB  - Although lymphatic filariasis remains among the major causes of disability among
      the tropical infectious diseases, dramatic advances have been made in the
      approach to its diagnosis, epidemiology and treatment, in our understanding of
      the molecular composition of the parasites that cause these infections, and in
      the factors underlying the pathology seen. Superimposing the tools of modern
      epidemiology, immunology, and molecular biology on field-based clinical trials
      has allowed the emergence of the concept of elimination of lymphatic filariasis.
      Much of the important new research emphasizes parasite development in the context
      of the host response, the importance of both the adult worm and other factors in
      the pathogenesis of lymphatic filarial disease, the role the Wolbachia
      endosymbiont holds as both a target for drug treatment and in inducing post
      treatment reactions, and the various principles underlying the implementation of
      control programs.

PMID- 11964874
TI  - Tropical diarrhoea: new developments in traveller's diarrhoea.
AB  - Traveller's diarrhoea is the most common illness acquired by visitors to
      developing countries, affecting 20-50% of the 35 million people who travel from
      industrialized countries each year. Important risk factors include point of
      origin and destination of the traveller, host factors, and exposure to
      contaminated food and water. The most common causes of traveller's diarrhoea in
      adults in developing countries include infection with Escherichia coli, Shigella
      spp., Salmonella spp., Campylobacter spp., Vibrio parahaemolyticus (in Asia),
      rotavirus (in Latin America), and protozoa (Giardia, Cryptosporidium and
      Cyclospora spp., and Entamoeba histolytica). No pathogen is identified in over
      half of patients with traveller's diarrhoea, however. The primary objectives of
      treatment of traveller's diarrhoea are to reduce the symptoms and duration of
      diarrhoeal illness, to reduce inconvenience caused by such illness and to prevent
      cancellation of planned activities. These important objectives are best
      accomplished by empirical self-therapy with a combination of antimicrobial agents
      and loperamide. Since the first use of ciprofloxacin, fluoroquinolones have
      become the drugs of choice in empirical therapy for moderate-to-severe
      traveller's diarrhoea in adults. The options for children include nalidixic acid,
      trimethoprim-sulfamethoxazole (along with erythromycin if Campylobacter infection
      is a possibility) and furazolidone. Education on hygiene and safe food
      preparation help to prevent many diarrhoeal diseases, including traveller's
      diarrhoea.

PMID- 11964875
TI  - Recent developments in cholera.
AB  - Cholera continues to be an important public health problem among many poorer
      communities in Africa, Asia and South America, despite the bacteriology and
      epidemiology of the disease having been described over a century ago. Molecular
      techniques have enabled current researchers to gain new insights into
      pathogenicity, into the relationships between environmental and clinical strains,
      and into new strategies for vaccine development. The description of non
      culturable 'dormant' strains in the environment and the effect of environmental
      factors on toxin gene regulation provide valuable clues to the ecology of the
      disease. Disease management continues to be based on urgent and appropriate
      rehydration, and recent community studies emphasize the need for effective local
      health services to provide this if case fatality rates are to remain low. While
      antimicrobial agents may play a role in case management and prophylaxis, the
      increasing prevalence of antimicrobial resistance must be addressed. New vaccine
      candidates, based on a molecular understanding of pathogenicity, provide scope
      for improved strategies for disease prevention, though the appropriate public
      health context for their use has not been determined. This review summarizes
      activities in these fields of cholera research and considers the continuing
      global problem of the disease.

PMID- 11964876
TI  - Intimate interactions of enteropathogenic Escherichia coli at the host cell
      surface.
AB  - Unlike many gastrointestinal pathogens, enteropathogenic Escherichia coli
      orchestrates the modulation of host cellular and immune responses from the
      exterior of the infected cell, chiefly via the secreted and translocated
      components of a type III secretion system. Close inspection of these
      enteropathogenic Escherichia coli proteins and the interactions they mediate
      provides an increasingly coherent picture of the pathogenic mechanisms that
      enteropathogenic Escherichia coli uses to exploit its host.

PMID- 11964877
TI  - Post-infective diarrhoea.
AB  - When diarrhoea caused by gastroenteritis persists for more than two weeks it is
      referred to as persistent diarrhoea in developing countries. Whilst the Control
      of Diarrhoeal Diseases programme has decreased mortality from acute diarrhoea,
      mortality from persistent diarrhoea has not been so responsive. A number of
      factors have been identified which are determinants for the progression of an
      acute episode to one which persists in developing communities. In one study from
      west Africa, current infection with Cryptosporidium parvum was the most
      significant factor. In studies from Brazil and India, continuing infection with
      enteropathogenic Escherichia coli was identified in 50% of infants with
      persistent diarrhoea. Persistent small intestinal mucosal damage is of key
      importance in such children. Management of established cases is complex and
      difficult. However, there is clear evidence that zinc is involved in the recovery
      of small intestinal mucosa after injury. Zinc supplementation may indeed
      significantly reduce the duration of persistent diarrhoea. However, the whole
      question of public health supplementation with zinc, vitamin A, or other
      supplements, is contentious at present.

PMID- 11964878
TI  - Typhoid fever: pathogenesis and disease.
AB  - Typhoid fever is an infectious disease of global distribution. Although there is
      a wealth of data on Salmonella typhimurium infection in the mouse and the
      interaction of this serovar with human cell lines in vitro, there is a relatively
      small amount of data on S. typhi and the pathogenesis of typhoid fever. In this
      review we focus on three areas: adherence to and invasion of gut epithelial
      cells, dissemination to systemic sites, and survival and replication within host
      cells. In addition, we attempt to put current salmonella research into the
      context of typhoid fever.

PMID- 11964879
TI  - Global aspects of antimicrobial-resistant enteric bacteria.
AB  - Antibiotics have been considered to be safe and effective 'magic bullets', with
      no disadvantages to their widespread use. This has been proven to be a complacent
      attitude, with ever-increasing prevalences of resistance now evident. The present
      review covers aspects of the development, mechanisms and genetics of
      antimicrobial resistance in enteric commensals and pathogens.

PMID- 11964880
TI  - Parasitic infections of the intestine.
AB  - Intestinal protozoal infections cause significant disease not only in the tropics
      but also in immunocompromised hosts and returning travellers in the developed
      world. Precise diagnosis of protozoal intestinal infection by microscopy can be
      difficult. Enzyme immunoassays for antigen detection are being used for some
      protozoal infections with some limitations which will, it is hoped, be overcome
      by molecular techniques. Nucleic acid amplification techniques could help improve
      detection of microsporidial species, which are difficult to detect
      microscopically and allow differentiation between Entamoeba histolytica and
      Entamoeba dispar. Definitive treatment for Cryptosporidium parvum infection
      remains elusive but new drugs are being evaluated. Cessation of thiabendazole
      production should not affect therapy of intestinal nematode infections as potent
      alternative therapy is available.

PMID- 11964881
TI  - Therapeutic advances in the management of hepatitis B and hepatitis C.
AB  - Until recently, interferon monotherapy has been the only available therapeutic
      option for patients with chronic hepatitis B and hepatitis C. Lamivudine has
      emerged as another effective first-line therapy for chronic hepatitis B as well
      as a beneficial treatment option for patients with decompensated hepatitis B
      cirrhosis. Viral resistance with long-term lamivudine therapy remains a major
      concern but new data continue to show benefits despite the development of YMDD
      mutations. Combination therapy with ribavirin and pegylated interferon-alpha has
      revolutionized the treatment of chronic hepatitis C. The rate of sustained
      virological response can now be expected to be as high as nearly 50% for genotype
      1 and 80% for non-1 genotypes of hepatitis C.

PMID- 11964882
TI  - Invasive mycoses: management and unmet medical needs.

PMID- 11964883
TI  - The role of yeasts other than Candida albicans in oropharyngeal candidiasis.
AB  - Candida albicans has been recognized as the predominant infecting organism in
      oropharyngeal candidiasis. Yeasts other than C. albicans are commonly recognized
      as colonizing the oral cavity but have not been thought to be a significant cause
      of disease. This review will describe the emergence of yeasts other than C.
      albicans as causative pathogens in oropharyngeal candidiasis both as co-infecting
      organisms with C. albicans and as sole pathogens themselves. Diagnosis and
      treatment of these emerging infections will also be discussed.

PMID- 11964884
TI  - Emergence of black moulds in fungal disease: epidemiology and therapy.
AB  - Black moulds are a heterogeneous group of darkly pigmented (dematiaceous) fungi,
      widely distributed in the environment, that occasionally cause infection in
      humans. The clinical spectrum of infection includes mycetomas,
      chromoblastomycosis, sinusitis, and superficial, cutaneous, subcutaneous and
      systemic phaeohyphomycosis. During the last 2 years, there have been reports of
      infection caused by black moulds in previously healthy individuals and in
      immunocompromised patients, including an outbreak of fungemia in hospitalized
      patients. Molecular analysis of strains obtained from patients and from the
      environment has suggested a common nosocomial source. In addition, data on
      antifungal susceptibility tests have become available. Surgical excision and
      antifungal therapy (usually itraconazole) remain the standard treatment for these
      infections.

PMID- 11964885
TI  - Clinical efficacy of echinocandin antifungals.
AB  - The prevalence of fungal infections has increased significantly over the past few
      decades. Candida and Aspergillus spp. are the most common fungal pathogens due to
      recent changes in medical technology. Amphotericin B continues to be the
      treatment of choice in many severe disseminated mycosis cases, but problems with
      toxicity, resistance and non-availability of an absorbable oral form are
      important drawbacks. The azoles offer a less toxic alternative but often they are
      not as effective as amphotericin B and resistance is an increasing problem. The
      echinocandins are new active antifungal agents with a novel mechanism of action.
      During the past year, one agent has been released and two others are undergoing
      advanced stages of investigation. Although these agents are not the ideal
      antifungal drug, they do offer new options of therapy.

PMID- 11964886
TI  - Coccidioidomycosis: efficacy of new agents and future prospects.
AB  - Recent studies have contributed to our understanding of risk factors for severe
      and potentially life-threatening infections with Coccidioides immitis, allowing a
      more rational approach to initiation of antifungal therapy for this infection, as
      well as determining its intensity and duration. A large randomized trial found
      that itraconazole and fluconazole had similar efficacies in the treatment of
      progressive nonmeningeal coccidioidomycosis. An animal model of coccidioidal
      meningitis suggested potential efficacy of systemically administered liposomal
      amphotericin B. Investigational agents that have activity against C. immitis
      include posaconazole, voriconazole, caspofungin, and sordarin derivatives.

PMID- 11964887
TI  - Extended-spectrum beta-lactamases: the European experience.
AB  - Extended-spectrum beta-lactamases mediate resistance to cephalosporin antibiotics
      and were first discovered in Europe in the early 1980s. They have become a
      widespread problem, particularly in Klebsiella pneumoniae, but increasingly in
      non-typhoid Salmonella species. Traditionally, extended-spectrum beta-lactamases
      have been derivatives of TEM and SHV parent enzymes. The last year, however, has
      seen an explosion of developments in extended-spectrum beta-lactamases of non
      TEM, non-SHV lineage in Europe. The CTX-M type extended-spectrum beta-lactamases
      have become particularly widespread. At the same time, European clinical
      microbiology laboratories have become more aware of the pressing need for
      detection methods given increasing awareness of the lack of reliability of
      cephalosporins in the treatment of extended-spectrum beta-lactamase producers.

PMID- 11964888
TI  - Severe community-acquired pneumonia: current outcomes, epidemiology, etiology,
      and therapy.
AB  - Severe community-acquired pneumonia is a clinical diagnosis with a significant
      impact on healthcare management around the world, with the highest morbidity and
      mortality of all of the forms of community-acquired pneumonia. Patients with
      severe pneumonia usually require intensive care unit management, including
      vasopressors or mechanical ventilation. Early clinical suspicion and prompt
      empiric antimicrobial therapies are mandatory in patients with severe pneumonia.
      A number of recent studies and guidelines addressing these issues have been
      published, and they will be reviewed in this article.

PMID- 11964889
TI  - Evidence for antibiotic cycling in control of resistance.
AB  - There is growing concern about the increasing rates of resistance among human
      pathogens. These high rates of resistance, which are a consequence of antibiotic
      misuse, highlight the need for a thorough revision of strategies that deal with
      the proper use of antibiotics. The so-called 'optimal use of all antibiotics',
      restriction guidelines and use of a combination of antibiotics are well
      established strategies in most hospitals but new potential strategies, such as
      dosage optimization and antibiotic cycling, require further study and evaluation.
      Cycling antibiotic therapy consists of the scheduled replacement of one
      antibiotic for another, in order to avoid the development of bacterial
      resistance. Initial studies suggest that this strategy could be useful in
      reducing the rates of bacterial resistance as well as the incidence of nosocomial
      infections caused by Gram-negative bacilli in intensive care unit patients. This
      strategy, however, does not prevent antibiotic misuse and needs to be applied in
      a complete antibiotic policy program.

PMID- 11964890
TI  - From natural products to drugs.

PMID- 11964891
TI  - Artemisinin and derivatives: the future for malaria treatment?
AB  - The isolation in 1972 of artemisinin by Chinese scientists, and their development
      of all the derivatives now used in the treatment of malaria today, were of
      outstanding importance. The results which have accumulated both from the Chinese
      work and from that subsequently conducted on a worldwide basis provide for a
      relatively comprehensive understanding of the chemistry, pharmacological
      profiles, toxicology, metabolism, and effects on the malaria parasite. The
      optimal regimens for use in the field are also apparent, particularly in
      combinations with longer half-life quinoline antimalarials. Thus the future use
      of the artemisinin class of drug appears assured. However, the mechanism of
      action needs to be clarified. More importantly from a clinical viewpoint,
      problems inherent in the current derivatives must be addressed, particularly that
      of neurotoxicity, if new artemisinin derivatives are to be introduced in a normal
      drug regulatory environment. The application of established principles of modern
      drug design should indeed allow for the first truly rationally designed, in so
      far as the target is still unknown, derivatives to come to hand.

PMID- 11964892
TI  - A new approach to the treatment of filariasis.
AB  - The symbiosis of filarial nematodes and intracellular Wolbachia bacteria has
      recently been exploited as a target for antibiotic therapy of filariasis.
      Antibiotic treatment of filarial nematodes results in sterility and inhibits
      larval development and adult worm viability. In the first trial on human
      onchocerciasis depletion of bacteria following treatment with doxycycline
      resulted in a complete and long-term block of embryogenesis. Bacteria are unable
      to repopulate nematode tissues up to 18 months after depletion, suggesting these
      effects may be permanent. Following ivermectin treatment, individuals given
      antibiotic therapy showed sustained reductions in skin microfilariae, with the
      majority of people remaining microfilarial negative 12-18 months after treatment.
      Since Wolbachia also contribute to the inflammatory pathogenesis of filarial
      disease, antibiotic therapy could, in addition to effects on worm fertility or
      viability, prevent the onset or development of filarial pathology.

PMID- 11964893
TI  - Specific treatment of Chagas disease: current status and new developments.
AB  - The current situation regarding specific chemotherapy for Chagas disease
      (American trypanosomiasis), and new developments in this field, are reviewed.
      Despite previous controversy on the autoimmune origin of Chagas disease
      pathology, available knowledge supports the notion that this condition should be
      treated as a parasitic, not an autoimmune, disease. Currently available drugs
      (nitrofurans and nitroimidazoles) are active in acute or short-term chronic
      infections, but have very low antiparasitic activity against the prevalent
      chronic form of the disease, and toxic side-effects are frequently encountered.
      The nitroimidazole benznidazole has also shown significant activity in the
      treatment of reactivated Trypanosoma cruzi infections in patients with acquired
      immune deficiency syndrome and in other immunosuppressed patients with underlying
      chronic Chagas disease. Although the etiological agent, T. (Schizotrypanum)
      cruzi, requires specific endogenous sterols for cell viability and proliferation,
      the currently available antifungal sterol biosynthesis inhibitors are not
      powerful enough to induce parasitological cures of human or experimental
      infections. However, new triazole antifungal compounds, which are potent
      inhibitors of the sterol C14alpha demethylase of the parasite and have special
      pharmacokinetic properties, are capable of inducing parasitological cures in
      murine models of both acute and chronic Chagas disease. They are currently the
      most advanced candidates for clinical trials in patients with Chagas disease.
      Other potential chemotherapeutic agents against T. cruzi currently in development
      include antiproliferative lysophospholipid analogs (already in clinical trials as
      the first oral treatment for visceral leishmaniasis), cysteine proteinase
      (cruzipain) inhibitors, and compounds that interfere with purine salvage and
      inositol metabolism.

PMID- 11964894
TI  - Hepatitis C virus cell culture replication systems: their potential use for the
      development of antiviral therapies.
AB  - Hepatitis C virus is a significant public health problem. Current drug regimens
      have low efficacy against some hepatitis C virus genotypes, while no vaccine is
      available. The absence of an efficient cell culture system and an accessible
      small animal model to study hepatitis C virus replication and pathogenesis are
      major obstacles to the development of effective antiviral therapies. Studies of
      surrogate model systems, either related viruses or chimeric viruses containing
      part of the hepatitis C virus genome, have given insight into hepatitis C virus
      replication, in addition to being a powerful tool for drug discovery. The recent
      development of an efficient system for the initiation of replication in cell
      culture provides a viable screen for inhibitors of hepatitis C virus replication.
      It also brings us much closer to the ultimate goal of an infectious cell culture
      system for hepatitis C virus.

PMID- 11964896
TI  - The mechanism of action of ribavirin: lethal mutagenesis of RNA virus genomes
      mediated by the viral RNA-dependent RNA polymerase.
AB  - Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole) is a broad-spectrum antiviral
      nucleoside that is currently used in combination with interferon-alpha to treat
      hepatitis C virus infection and as a monotherapy to treat severe cases of
      respiratory syncytial virus infection and Lassa fever virus infection. The
      mechanism of action of ribavirin has been studied for decades. These studies have
      suggested that the antiviral activity of ribavirin may be related to its ability
      to cause a decrease in intracellular guanosine triphosphate pools, to inhibit
      capping of viral transcripts or to suppress humoral and cellular immune
      responses. Last year, another possibility was added to this list. The new
      proposition is that ribavirin, when converted to the triphosphate, is utilized by
      the viral RNA-dependent RNA polymerase and causes lethal mutagenesis of the viral
      genome. In this article, the data supporting this new hypothesis are reviewed. We
      discuss the implications of these data on alternative explanations for the
      apparent failure of ribavirin monotherapy in the treatment of hepatitis C virus
      infection, connections between developmental defects induced by ribavirin and
      posttranscriptional gene silencing/RNA interference, and the use of lethal
      mutagenesis and related concepts as strategies for antiviral therapy.

PMID- 11964895
TI  - The impact of HIV therapy on co-infection with hepatitis B and hepatitis C
      viruses.
AB  - Improving survival for people with HIV has brought management of co-morbidities
      into focus. In the era of highly active antiretroviral therapy, co-infection with
      either hepatitis B virus and/or hepatitis C virus, and HIV therapies themselves,
      have increased liver disease-related morbidity and mortality. The dual anti-HIV
      and anti-hepatitis B activity of several established and emerging therapeutic
      agents provides the opportunity to both restore immune function and prevent liver
      disease progression in people with HIV-hepatitis B virus co-infection. Improving
      hepatitis C antiviral therapy also provides optimism around management of liver
      disease in people with HIV-hepatitis C virus co-infection. However, formulation
      of appropriate therapeutic strategies for HIV-hepatitis B and HIV-hepatitis C co
      infection requires further research, including clinical trials of combination
      antiviral therapy with specific anti-hepatitis B and anti-hepatitis C activity. A
      possible role may also exist for combined antiviral and immune-based therapies.

PMID- 11964897
TI  - Cytomegalovirus therapy: current constraints and future opportunities.
AB  - Articles published in the last year have changed perceptions of cytomegalovirus.
      It is now recognized as a rapidly replicating virus which develops resistance
      frequently during chronic administration of ganciclovir. In addition to causing
      end-organ diseases, it plays a causal role in the multifactorial processes
      leading to graft rejection after renal transplant and accelerated atherosclerosis
      after heart transplant. New treatments which are safe and potent are urgently
      needed and should be highly cost-effective when the full clinical impact of this
      virus is assessed.

PMID- 11964899
TI  - Intracellular pharmacology of nucleoside analogues and protease inhibitors: role
      of transporter molecules.
AB  - Antiretroviral agents target HIV replication within infected cells. It is
      therefore important to focus on the pharmacology of these drugs at their site of
      action rather than just in plasma. Activation of nucleoside analogues to a
      triphosphate is essential for antiretroviral activity. Following activation, by
      intracellular kinases, drug triphosphates compete with endogenous triphosphates
      for HIV reverse transcriptase. Methodologies to measure triphosphates in
      peripheral blood mononuclear cells from HIV patients have been described. This
      has allowed investigation of once-daily dosing regimens, drug interactions,
      modulation of intracellular activation and the bypassing of initial
      phosphorylation steps. Drug accumulation within a cell is a balance between
      influx and efflux. There is a growing body of evidence indicating that transport
      proteins are vitally important in regulating intracellular concentrations of
      antiretroviral drugs. Allelic variants, inhibition (or induction) are all
      potentially critical determinants of active drug present in the cell. It is hoped
      that understanding the intracellular pharmacology will improve long-term therapy
      and reduce the likelihood of cellular resistance in therapeutic failure.

PMID- 11964900
TI  - Methods of assessing body shape and composition in HIV-associated lipodystrophy.
AB  - Although HIV-associated lipodystrophy can be diagnosed just from clinical
      examination, criteria for diagnosis and judgement of severity are not clearly
      defined. Clinical assessment can be systematized with questionnaires for patients
      and physicians. Computed tomography, nuclear magnetic imaging and dual-energy X
      ray absorptiometry are objective reference methods but are expensive for routine
      follow-up and diagnosis. Therefore, anthropometry and other non-invasive bedside
      methods deserve further validation studies.

PMID- 11964901
TI  - Pros and cons of therapeutic drug monitoring of antiretroviral agents.
AB  - Therapeutic drug monitoring has the promise to become a part of routine patient
      care in the treatment of HIV infection. It is known that plasma drug
      concentrations of protease inhibitors and non-nucleoside reverse transcriptase
      inhibitors are better predictors of antiviral response or toxicity than drug dose
      is. Furthermore, high interpatient variability is significant. In addition,
      therapeutic drug monitoring may be used as a direct and objective instrument to
      measure non-adherence. This review describes possibilities and limitations of
      therapeutic drug monitoring in HIV treatment.

PMID- 11964902
TI  - Hyperlactatemia syndromes in people with HIV infection.
AB  - Hyperlactatemia associated with use of nucleoside analogue reverse transcriptase
      inhibitors (NRTIs) is not a single entity but a spectrum of abnormalities. The
      spectrum reflects varying degrees of derangement in systemic homeostasis in the
      face of primary drug effects on lactate load. Lactic acidosis, characterized by
      metabolic acidosis, blood lactate above 5 mmol/l, hepatic steatosis and high
      mortality, represents the extreme end of this spectrum where there is complete
      decompensation. Partially compensated states of lactate excess have now been
      described, ranging from less fulminant symptomatic hyperlactatemia with hepatic
      steatosis to chronic or intermittent low-grade hyperlactatemia without acidosis,
      steatosis or any symptoms. At a population level, average venous lactate
      concentrations do rise following treatment with NRTIs but stabilize long term in
      the majority of cases. The average increase in systemic lactate turnover that is
      required to maintain such compensated blood levels is not known and research into
      this may provide insights into the extent of incipient mitochondrial toxicity
      associated with chronic NRTI use. At a tissue-specific level, it is not known
      which tissues or organs (liver, fat, other) are the predominant contributors to
      an increase in systemic lactate load, nor whether the primary defect is one of
      increased production, decreased elimination or both.

PMID- 11964903
TI  - Chlamydia screening in primary care: is it useful, affordable and universal?
AB  - Genital chlamydial infection, with its possible long-term morbidity, is a serious
      public health problem. The number of new diagnoses is rising rapidly and, in the
      UK, recent evidence suggests that the infection rate in young women exceeds 10%.
      Screening programmes can reduce the population prevalence of infection, but
      uncertainty remains as to the ideal screening model. This may prove to be
      opportunistic screening of sexually active young women, less than 25 years of
      age, in primary care settings, and contact tracing of the partners of those with
      chlamydia. Recent literature on the practicalities of genital chlamydia screening
      is reviewed.

PMID- 11964904
TI  - Risk behaviour and sexually transmitted diseases are on the rise in gay men, but
      what is happening with HIV?
AB  - Increases in sexually transmitted diseases and sexual risk behaviour among men
      who have sex with men in the Western world have raised concern with regard to the
      HIV/AIDS epidemic in this group. The aim of this review is to give an overview of
      possible explanations for these alarming increases and to indicate what impact
      they might have on this epidemic.

PMID- 11964905
TI  - Haemophilus ducreyi: clinical disease and pathogenesis.
AB  - Haemophilus ducreyi causes the sexually transmitted disease chancroid, which
      facilitates the transmission of HIV infection. This review focuses on recent
      advances in the epidemiology, diagnosis, treatment and pathogenesis of this
      disease.

PMID- 11964906
TI  - New treatments for genital herpes.
AB  - Genital herpes is a sexually transmitted disease that has been widely
      investigated from both an epidemiological and a diagnostic viewpoint. Better
      knowledge of the disease has pointed to the important role of asymptomatic herpes
      simplex virus type 2 shedding as a major culprit for the spread of the virus in
      the world, the latest statistics showing that the incidence of genital herpes is
      constantly increasing. The reference compound for the treatment and prophylaxis
      of genital herpes is acyclovir. Recently, two drugs with better oral
      bioavailability, valaciclovir, the oral prodrug of acyclovir, and famciclovir,
      the oral prodrug of penciclovir, have been made available. Nevertheless, there is
      a need to develop additional approaches, to extend the therapeutic possibilities
      and to face the problem of emerging resistant viruses, mostly in
      immunocompromised patients. Therefore, efforts have been made in different
      directions including the exploration of new targets for antiviral chemotherapy,
      the use of immunomodulators and the development of specific vaccines.

PMID- 11964907
TI  - Vaginal microbicides.
AB  - The focus of this review will be to highlight articles from 2000 and up to August
      2001 that demonstrate the challenges in the evaluation of candidate microbicides,
      and the ways in which investigators have approached these challenges.

PMID- 11964908
TI  - Scytalidium infections.

PMID- 11964909
TI  - Human papillomaviruses and non-melanoma skin cancer.
AB  - Epidemiological and experimental studies have overwhelmingly confirmed human
      papillomaviruses as important causal agents in anogenital carcinogenesis. A role
      for human papillomaviruses has also been proposed in a diverse range of other
      malignancies, and particular interest has focused on non-melanoma skin cancer,
      the commonest malignancy in fair-skinned populations worldwide. Although the
      evidence for this is considerably less convincing than for anogenital cancer,
      important epidemiological and functional data have emerged over the past year
      that have furthered our understanding of the possible contribution of human
      papillomaviruses to skin cancer. Epidemiological human papillomavirus DNA
      detection studies have shown associations with non-melanoma skin cancer, but have
      also emphasized the ubiquity of epidermodysplasia verruciformis human
      papillomavirus types in normal skin, hair follicles and benign hyperproliferative
      disorders, as have seroepidemiological approaches. Functional investigations have
      demonstrated mechanistically relevant interactions between the virus and
      ultraviolet radiation, host cytokines and cellular proteins including p53 and the
      pro-apoptotic protein Bak. Taken together, these data have advanced our
      understanding of the contribution of human papillomaviruses to malignant
      transformation in cutaneous keratinocytes, but further research is required
      before a causal association between human papillomaviruses and skin cancer is
      reliably confirmed.

PMID- 11964910
TI  - The management of herpes simplex virus infections.
AB  - Herpes simplex virus persists in a latent form for the life of its host,
      periodically reactivating and often resulting in significant psychosocial
      distress for the patient. Currently no cure is available. Antiviral therapy is
      the main treatment modality, used either orally, intravenously, or topically to
      prohibit further replication of the virus and thereby minimize cellular
      destruction. However, immunologic advances in the treatment and prevention of
      herpes simplex infections are promising and continue to be studied.

PMID- 11964911
TI  - Ivermectin in scabies.
AB  - The standard treatment for scabies has long been based on topical scabicides.
      Ivermectin, a broad-spectrum anti-parasitic agent, was first used in veterinary
      medicine. This drug, active against nematodes and arthropods, is used in humans
      for the treatment of filariasis. For the past few years worldwide reports on the
      use of ivermectin in human scabies have suggested that this drug could be an
      alternative oral therapy.

PMID- 11964912
TI  - Melioidosis.
AB  - Melioidosis is an important public health problem in some regions, and a
      potential bioweapon. Recent reports confirm that it is endemic in China, Taiwan
      and Laos, but the true incidence in most countries is unknown, and the ecology
      poorly understood. Potable water was the source of two recent outbreaks. The
      epidemiology and clinical manifestations of the disease in Australia are similar
      to those in Thailand, although prostatic abscesses and neurological
      manifestations are more common and parotid abscesses less so. Mycotic aneurysms
      are not uncommon. Patients with cystic fibrosis are at risk of pulmonary
      melioidosis. Comparison with the avirulent Burkholderia thailandensis has
      identified capsular polysaccharide as an important virulence determinant in
      Burkholderia pseudomallei. Diagnosis still relies on culture, and a throat swab
      is a worthwhile sample. Several beta-lactams, such as meropenem, reduce the
      mortality, and long courses of cotrimoxazole-containing regimes are needed to
      prevent relapse. The value of adjunctive treatments, such as granulocyte colony
      stimulating factor, warrants further evaluation.

PMID- 11964913
TI  - Malassezia species in skin diseases.
AB  - Since the taxonomic revision carried out in 1996, enlarging the genus Malassezia
      to comprise seven different species, a number of studies have investigated from
      different points of view -- mycological, molecular and immunological -- the
      relationships of these species with the pathologies associated with lipophilic
      yeasts, as well as its presence in healthy skin. From these studies, it now
      appears clear that Malassezia globosa is the main species associated with
      pityriasis versicolor, which is the only cutaneous disease in which the
      involvement of Malassezia is undisputed. Nevertheless, this species can also be
      found in normal skin, in which the predominant species is Malassezia sympodialis.
      In the remaining dermatological disorders related to Malassezia, the role of
      these yeasts is controversial. In seborrhoeic dermatitis, atopic dermatitis and
      folliculitis, several studies have focused on the immunological aspects that
      could explain the pathogenic mechanism. In other diseases, such as confluent and
      reticulate papillomatosis, neonatal pustulosis, otitis and onychomycosis, the
      presence or significance of Malassezia is still a matter of dispute.

PMID- 11964915
TI  - Judicious use of antibiotics to treat respiratory tract infections.

PMID- 11964914
TI  - New perspectives on the immunology of chronic mucocutaneous candidiasis.
AB  - Chronic mucocutaneous candidiasis is a primary immune deficiency presenting as an
      inability to clear fungal infections and consequently as persisting and recurring
      infections of the skin and mucous membranes with yeasts, mostly Candida albicans.
      Chronic mucocutaneous candidiasis is a heterogeneous clinical syndrome which
      usually presents in childhood and can have an autosomal recessive, dominant or
      sporadic mode of inheritance. Most chronic mucocutaneous candidiasis patients
      also develop accompanying endocrine and inflammatory disorders that suggest an
      underlying deregulation of the immune system. It has long been recognized that
      protection from mucocutaneous candidiasis relies on cell-mediated immunity and
      studies on animal models have highlighted the essential role of type 1 cytokines
      in protection against Candida spp. Recent data in patients with chronic
      mucocutaneous candidiasis have documented altered patterns of cytokine production
      in response to Candida spp. with decreased production of some but not all type 1
      cytokines and increased levels of interleukin-10. The defect underlying altered
      cytokine production remains unknown but studies are in progress addressing the
      putative role of dendritic cells and pattern recognition receptors in directing
      cytokine responses. These novel insights into immune mechanisms responsible for
      protection against Candida spp. are opening new possibilities of immunomodulation
      and vaccination that could prove beneficial in the management of chronic
      mucocutaneous candidiasis.

PMID- 11964916
TI  - Appropriate use of antibiotics for respiratory infections: review of recent
      statements and position papers.
AB  - Respiratory infections are among the most common reasons for prescribing
      antibiotics. The excessive use of antibiotics in ambulatory practice has
      contributed to the emergence and spread of antibiotic resistance. The appropriate
      use of antimicrobial agents for respiratory infections could potentially reduce
      the emergence of antibiotic resistance. This article reviews recent guidelines
      and position papers on the appropriate antibiotic treatment for respiratory
      infections. There is a wide consensus that antibiotics are not appropriate for
      the treatment of most cases of acute bronchitis, pharyngitis, and rhinosinusitis.
      The recently published community-acquired pneumonia guidelines emphasized the
      importance of selecting antibiotic regimens active against both typical and
      atypical pathogens. However, there is disagreement regarding the routine use of
      the new quinolones.

PMID- 11964917
TI  - Etiology and management of community-acquired pneumonia in Asia.
AB  - The causative organisms of community-acquired pneumonia, especially in Japan and
      Korea, are essentially similar to those in Western countries. If there are any
      differences, these are due to the laboratory tests and criteria used to define
      pathogenicity. Overall, Streptococcus pneumoniae is the most frequently occurring
      pathogen and Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae
      and viruses follow. Legionella spp. look likely to be low frequency pathogens in
      Asian countries, but a reason for this might be limitations of the laboratory
      tests used. A high frequency of Gram-negative bacilli as pathogens of community
      acquired pneumonia in some Asian countries may be due to different criteria used
      to identify disease-causing organisms. A small number of papers about antibiotic
      resistance have shown no large differences between Asian countries, but
      considerable differences to Western countries, such as frequency of macrolide
      resistant S. pneumoniae. Some Asian countries have their own guidelines for
      community-acquired pneumonia, but these are written in their own languages.

PMID- 11964918
TI  - Update on community-acquired pneumonia: impact of antibiotic resistance on
      clinical outcomes.
AB  - In contrast to the rapid expansion in the number of published studies reporting
      the increasing rate of antimicrobial drug resistance among common respiratory
      pathogens, there remain few controlled studies examining the impact of these
      trends on clinical outcomes. Those studies that are published are hampered by
      small sample sizes, biases inherent in observational designs, and the relative
      infrequency of isolates showing high-level resistance, particularly high-level
      beta-lactam resistance among clinical isolates of Streptococcus pneumoniae. This
      update summarizes recent published studies addressing the impact of drug
      resistance on outcomes for lower respiratory tract infections. The majority of
      these studies are retrospective cohort studies, focusing on the impact of beta
      lactam-resistant pneumococcal infections in patients with community-acquired
      pneumonia. These studies support the conclusion that current levels of
      pneumococcal drug resistance do not result in clinical treatment failures for
      patients with community-acquired pneumonia. However, as patterns of drug
      resistance evolve, future studies will be needed to address the continued
      appropriateness of current empirical treatment guidelines for these patients.

PMID- 11964919
TI  - Community-acquired pneumonia: process of care studies.
AB  - New insight has been gained into the relationship between the processes of care
      undertaken for patients with community-acquired pneumonia and the resulting
      outcomes. Better insight into the risks for a complicated course can increase the
      percentage of patients treated as outpatients. Studies have also suggested that
      both the promptness and the choice of antibiotic therapy can affect patient
      outcomes. Promptly switching to oral antibiotic therapy can often lead to a
      shorter length of hospital stay; however, concern has arisen regarding the effect
      of shorter lengths of stay on patient outcomes.

PMID- 11964920
TI  - Cystic fibrosis.
AB  - Cystic fibrosis is the most common lethal inherited disorder with autosomal
      recessive inheritance. Major progress has been made in understanding the
      molecular mechanisms leading to increased susceptibility to Pseudomonas
      aeruginosa colonization. Persistent respiratory infection with P. aeruginosa
      leads to progressive pulmonary inflammation and is the major cause of morbidity
      and mortality. Treatment and prophylaxis of respiratory infection has improved
      the median survival and quality of life of cystic fibrosis patients. In the
      future, treatment of the underlying genetic defect may be possible.

PMID- 11964922
TI  - "State of the journal" - 2002.

PMID- 11964921
TI  - Recent advances in the epidemiology, prevention, diagnosis, and treatment of
      fungal pneumonia.
AB  - Although pneumonia caused by fungi is not a common occurrence in the general
      population, disease in an enlarging immunocompromised population is encountered
      with increasing frequency. Fungal pneumonias are most frequently caused by
      Aspergillus spp., dimorphic fungi and Cryptococcus neoformans. Recent studies
      have identified risk factors of thrombocytopenia, environmental events (such as
      construction or renovation) and immunosuppressive drug therapies as being
      specific risk factors for invasive fungal disease in select patient populations.
      Diagnostic strategies to detect circulating antigens and polymerase chain
      reaction based detection systems have been explored to improve identification
      prior to the progressive advanced disease. Advances in prophylactic strategies
      include increased use of aerosolized formulations of amphotericin B, usually in
      conjunction with new and old systemic antifungal agents. Despite recent published
      guidelines for treatment of fungal pneumonia based on etiology, mortality remains
      high in some infections with advanced disease. Caspofungin, a new echinocandin
      antifungal, has recently been approved by the US Food and Drug Administration for
      the treatment of invasive Aspergillus infections in patients unresponsive to or
      unable to receive amphotericin B. A triazole antifungal, voriconazole, has shown
      promise in phase III clinical trials in patients with refractory fungal
      infections and is expected to be available in early 2002. Other echinocandin and
      triazole antifungals are under development in attempts to provide improved
      effective therapy for fungal pneumonia.

PMID- 11964923
TI  - Epidemiology: new access, new opportunity.

PMID- 11964924
TI  - DNA banking for epidemiologic studies: a review of current practices.
AB  - To study genetic risk factors for common diseases, researchers have begun
      collecting DNA specimens in large epidemiologic studies and surveys. However,
      little information is available to guide researchers in selecting the most
      appropriate specimens. In an effort to gather the best information for the
      selection of specimens for these studies, we convened a meeting of scientists
      engaged in DNA banking for large epidemiologic studies. In this discussion, we
      review the information presented at that meeting in the context of recent
      published information. Factors to be considered in choosing the appropriate
      specimens for epidemiologic studies include quality and quantity of DNA,
      convenience of collection and storage, cost, and ability to accommodate future
      needs for genotyping. We focus on four types of specimens that are stored in
      these banks: (1) whole blood preserved as dried blood spots; (2) whole blood from
      which genomic DNA is isolated, (3) immortalized lymphocytes from whole blood or
      separated lymphocytes, prepared immediately or subsequent to cryopreservation;
      and (4) buccal epithelial cells. Each of the specimens discussed is useful for
      epidemiologic studies according to specific needs, which we enumerate in our
      conclusions.

PMID- 11964925
TI  - Breast cancer risk in Ashkenazi BRCA1/2 mutation carriers: effects of
      reproductive history.
AB  - BACKGROUND: Younger age at first birth and greater parity generally reduce the
      risk of developing breast cancer, but whether this reduced risk holds in women
      with a mutation in the BRCA1 or BRCA2 gene is unknown. METHODS: In a Washington
      DC community-based study conducted in 1996, we tested 5318 Ashkenazi Jews for
      three BRCA1/2 founder mutations and identified 120 mutation carriers. Applying an
      extension of the "kin-cohort" analysis, we compared the effects of reproduction
      on breast cancer risk in carriers and noncarriers. We also used a case-case
      analysis among 288 participants who had been diagnosed with breast cancer.
      RESULTS: In noncarriers, the estimated relative risk (RR) of breast cancer rose
      5% with each 5-year increment in age at first birth (RR = 1.05; 95% confidence
      interval [CI] = 0.97-1.15). By contrast, the estimated risk in mutation carriers
      fell with each 5-year increment in age (RR = 0.65; 95% CI = 0.37-1.16). Among the
      288 participants who were breast cancer survivors themselves, the comparison of
      carriers with noncarriers also showed no protection associated with early birth
      in the presence of a mutation in BRCA1 or BRCA2. CONCLUSIONS: It is not yet clear
      whether the recognized breast cancer risk factors operate in the same way in
      women who carry a mutation in the BRCA1 or BRCA2 genes.

PMID- 11964926
TI  - Statin use and the risk of breast and prostate cancer.
AB  - BACKGROUND: Laboratory data suggest that the cholesterol-lowering "statin" drugs
      may have chemopreventive potential against cancer at various sites, including
      breast and prostate. However, in one trial of pravastatin there was a significant
      excess of breast cancer in the treatment group. In the present study, we assessed
      the relation of statin use to the risk of breast and prostate cancer in our
      hospital-based Case-Control Surveillance Study of Drugs and Serious Illnesses.
      METHODS: Cases were 1,132 women with breast cancer and 1,009 men with prostate
      cancer; controls were 1,331 women and 1,387 men admitted for conditions unrelated
      to statin use. We used multivariate unconditional logistic regression models to
      estimate odds ratios (ORs) and 95% confidence intervals (CIs) for use of statins
      compared with no use. RESULTS: The OR for breast cancer among statin users was
      1.5 (95% CI = 1.0-2.3), largely accounted for by an OR of 1.8 (95% CI = 0.9-3.6)
      among cases with carcinoma in situ. Among invasive cases, the OR was 1.2 (95% CI
      = 0.7-2.0). The odds ratio for prostate cancer overall was 1.2 (95% CI = 0.8
      1.7), and it was 1.4 (95% CI = 0.7-2.5) for Stage A. CONCLUSIONS: The data from
      the present study do not support a protective effect of statins against breast or
      prostate cancer. Detection bias is a possible explanation for the higher ORs
      observed for carcinoma in situ or early-stage cancer as compared with more
      invasive cancer.

PMID- 11964927
TI  - Leanness and lung cancer risk: fact or artifact?
AB  - BACKGROUND: More than a dozen studies have examined the association between
      leanness and increased lung cancer risk. None of the prospective studies has been
      large enough to allow exclusion of smokers or persons with preexisting disease,
      two factors that cause both leanness and poor survival and thus may cause a
      spurious association between low body mass index and fatal lung cancer. METHODS:
      Using Cox proportional hazards models, we examined this issue in a cohort of
      941,105 U.S. adults enrolled in an American Cancer Society prospective study in
      1982. During 14 years of follow-up, 14,066 people died of lung cancer. RESULTS:
      In analyses restricted to lifelong nonsmokers who did not report preexisting
      disease, leanness was not substantially associated with lung cancer mortality in
      men (rate ratio = 0.9; 95% confidence interval = 0.3-3.1) or in women (rate ratio
      = 1.2; 95% confidence interval = 0.7-2.1). However, leanness was associated with
      increased lung cancer risk in analyses that attempted to control for, rather than
      exclude, smokers and persons with preexisting disease. CONCLUSIONS: These data
      suggest that the association between leanness and lung cancer mortality is not
      causal but rather is an artifact of the effects of smoking and preexisting
      disease.

PMID- 11964928
TI  - Childhood acute lymphoblastic leukemia associated with parental alcohol
      consumption and polymorphisms of carcinogen-metabolizing genes.
AB  - BACKGROUND: Limited information is available on the association of parental
      consumption of alcohol prior to and during pregnancy with the risk of childhood
      leukemia, as well as for the potentially modifying role of genetic polymorphisms.
      METHODS: We conducted a population-based, case-control study of 491 incident
      cases of acute lymphoblastic leukemia age 0-9 years and matched on age and sex to
      491 healthy controls. Cases were identified at tertiary care centers in the
      Province of Quebec between 1980 and 1993. Each parent was interviewed separately
      about alcohol consumption habits. We also used a case-only design with 186 cases
      to estimate interaction odds ratios between prenatal exposure and child DNA
      variants in the GSTM1 and CYP2E1 genes. RESULTS: The adjusted odds ratio for any
      maternal consumption during pregnancy was 0.7 (95% confidence interval = 0.5
      0.9). The interaction odds ratios for the GSTM1 null genotype during third
      pregnancy trimester was 2.4 (95% confidence interval = 1.1-5.4); the interaction
      odds ratio for CYP2E1 variant G-1295C (or allele *5) during the nursing period
      was 4.9 (95% confidence interval = 1.5-16.7). CONCLUSIONS: The observed
      association with maternal alcohol consumption during pregnancy could be due to
      the potential chemopreventive effects of flavonoids found in wine and beer. These
      possible effects of alcohol may be at least partially genetically determined,
      although data are preliminary.

PMID- 11964929
TI  - Risk factors for febrile convulsions.
AB  - BACKGROUND: Little is known about the relative importance of genes and early
      environment in the etiology of febrile convulsions. METHODS: We performed a
      follow-up study using data from two nationwide registers in Denmark, 1980-1998.
      The study population comprised 10,224 younger siblings of children who had had
      febrile convulsions, and 21,218 younger siblings of children who had never been
      hospitalized with febrile convulsions. RESULTS: The study provides three main
      findings. First, if a previous child had had a febrile convulsion, the risk was
      lower for the next child if either parent changed partners. Compared with full
      siblings, the hazard ratio (HR) of febrile convulsions was 0.6 for paternal half
      siblings and 0.7 for maternal half-siblings. In contrast, if there was no history
      of febrile convulsions in the previous child, a change in partner was associated
      with a slight increase in risk (1.2 among paternal half-siblings and 1.3 among
      maternal half-siblings). Secondly, the risk of febrile convulsion was strongly
      associated with the number of hospitalizations for febrile convulsions
      experienced by the older siblings, with a doubling of risk among those whose
      older sibling had had three or more hospitalizations. Thirdly, the risk of
      febrile convulsions increased with decreasing gestational age, birth weight, and
      birth weight ratio regardless of family history. CONCLUSIONS: Our data suggest
      that the etiology of febrile convulsions depends on a genetic susceptibility that
      can be transmitted through both parents, and corroborates the hypothesis that
      multiple febrile convulsions may constitute a separate etiological entity.

PMID- 11964930
TI  - Indoor risk factors for asthma in a prospective study of adolescents.
AB  - BACKGROUND: The risk of asthma associated with pets and other indoor exposures
      has been examined in both cross-sectional and prospective studies of younger
      children. However, there has been little investigation of the effect of the
      indoor environment on incident asthma in adolescents. METHODS: Risk factors for
      the development of asthma were examined in a cohort of 3535 Southern California
      school children with no history of asthma at 1993 entry into the study, who were
      followed for up to 5 years. Newly diagnosed cases of asthma were identified by
      yearly interview report. A total of 265 children reported a new diagnosis of
      asthma during the follow-up period; 163 of these had reported no history of
      wheeze at baseline. The risk associated with indoor exposures assessed by
      questionnaire at entry into the study was examined using Cox proportional hazards
      models. RESULTS: In children with no history of wheezing, an increased risk of
      developing asthma was associated with a humidifier (relative risk [RR] = 1.7; 95%
      confidence interval [CI] = 1.2-2.4), any pet (RR = 1.6; 95% CI = 1.0-2.5), or
      specifically a dog (RR = 1.4; 95% CI = 1.0-2.0) in the home. An estimated 32% of
      new asthma cases could be attributed to pets. CONCLUSIONS: We conclude that furry
      pets are a common and potentially remediable risk factor for new onset asthma in
      adolescents. Our results suggest that a humidifier in the home may contribute to
      the onset of asthma in this age group.

PMID- 11964931
TI  - Indoor particles and symptoms among office workers: results from a double-blind
      cross-over study.
AB  - BACKGROUND: We studied the effects of removing small airborne particles in an
      office building without unusual contaminant sources or occupant complaints.
      METHODS: We conducted a double-blind crossover study of enhanced particle
      filtration in an office building in the Midwest United States in 1993. We
      replaced standard particle filters, in separate ventilation systems on two
      floors, with highly efficient filters on alternate floors weekly over 4 weeks.
      Repeated-measures models were used to analyze data from weekly worker
      questionnaires and multiple environmental measurements. RESULTS: Bioaerosol
      concentrations were low. Enhanced filtration reduced concentrations of the
      smallest airborne particles by 94%. This reduction was not associated with
      reduced symptoms among the 396 respondents, but three performance-related mental
      states improved; for example, the confusion scale decreased (-3.7%; 95%
      confidence limits (CL) = -6.5, -0.9). Most environmental dissatisfaction
      variables also improved; eg, "stuffy" air, -5.3% (95% CL = -10.3, -0.4). Cooler
      temperatures within the recommended comfort range were associated with remarkably
      large improvement in most outcomes; for example, chest tightness decreased -23.4%
      (95% CL = -38.1, -8.7) for every 1 degrees C decrease. CONCLUSIONS: Benefits of
      enhanced filtration require assessment in buildings with higher particulate
      contaminant levels in studies controlling for temperature effects. Benefits from
      lower indoor temperatures need confirmation.

PMID- 11964932
TI  - The association between personal measurements of environmental exposure to
      particulates and heart rate variability.
AB  - BACKGROUND: Epidemiologic evidence indicates that airborne particulates are
      associated with mortality risk, predominately from heart disease. This may occur
      through changes in the cardiac autonomic nervous system, witnessed by changes in
      heart rate variability. METHODS: This short-term longitudinal study used
      continuous personal particulate matter measurements to examine the effects of
      exposure to particulate matter less than 2.5 microm in diameter (PM2.5) on heart
      rate and rate variability in 20 relatively young, healthy male workers.
      Continuous exposure and cardiac monitoring were performed on each subject on a
      nonwork day. The 5-minute standard deviation of the normal-to-normal interval was
      used as the main measure of heart rate variability. RESULTS: Mixed-effects
      regression models estimate an average 1.4% (95% confidence limits = -2.1, -0.6)
      decrease in the 5-minute standard deviation of the normal-to-normal interval for
      each 100 microg/m3 increase in the 3-hour PM2.5 moving average, and small
      increases in heart rate, after adjustment for potential confounding factors.
      Predicted effects of exposure were greatest using the 3-hour averaging interval
      for PM2.5 and decreased in magnitude using shorter and longer intervals.
      CONCLUSIONS: These results reveal an association between cardiac autonomic
      function and environmental PM2.5 exposure. These observed associations may result
      from decreased vagal or increased sympathetic tone.

PMID- 11964933
TI  - Lead exposure and amyotrophic lateral sclerosis.
AB  - BACKGROUND: Previous interview-based studies have suggested that exposure to
      neurotoxicants including metals might be related to ALS. METHODS: We evaluated
      the relation of lead exposure to ALS, using both biological measures and
      interviews, in a case-control study conducted in New England from 1993 to 1996.
      Cases (N = 109) were recruited at two hospitals in Boston, MA. Population
      controls (N = 256) identified by random-digit dialing were frequency-matched to
      cases by age, sex, and region of residence within New England. RESULTS: Risk of
      ALS was associated with self-reported occupational exposure to lead (odds ratio
      [OR] = 1.9; 95% confidence interval [CI] = 1.1-3.3), with a dose response for
      lifetime days of lead exposure. Blood and bone lead levels were measured in most
      cases (N = 107) and in a subset of controls (N = 41). Risk of ALS was associated
      with elevations in both blood and bone lead levels. ORs were 1.9 (95% CI = 1.4
      2.6) for each microg/dl increase in blood lead, 3.6 (95% CI = 0.6-20.6) for each
      unit increase in log-transformed patella lead, and 2.3 (95% CI = 0.4-14.5) for
      each unit increase in log-transformed tibia lead. CONCLUSIONS: These results are
      consistent with previous reports and suggest a potential role for lead exposure
      in the etiology of ALS.

PMID- 11964934
TI  - Concurrent sexual partnerships among women in the United States.
AB  - BACKGROUND: The marked racial disparity in sexually transmitted infection (STI)
      rates in the United States remains inadequately explained. One important factor
      may be concurrent sexual partnerships (relationships that overlap in time), which
      can transmit STIs more rapidly through a population than does sequential
      monogamy. METHODS: To determine prevalence, distribution, and correlates of U.S.
      women's involvement in concurrent partnerships, we analyzed sexual partnership
      data reported by the 10,847 women, age 15-44 years, in the 1995 National Survey
      of Family Growth. Overlapping sexual partnership dates were determined by
      computer program and visual review of the data. RESULTS: Prevalence of concurrent
      partnerships since January 1991 was 12% overall. Prevalence was lowest among
      currently married respondents (4%) and highest among those who were formerly
      married (22%), never married (19%), in the lowest income stratum (17%), age 18-24
      years when interviewed (23%), or who first had sexual intercourse at age 12 or 13
      (35%). Prevalence was 21% among blacks, 11% among whites, 8% among Hispanics, and
      6% among Asian American and Pacific Islanders. Multiple logistic analysis
      substantially weakened the relationship between concurrency and black race (OR =
      1.2; 95% CI = 1.1-1.4). CONCLUSIONS: Marital status in particular is strongly
      related to concurrency; thus, lower marriage rates among blacks and the
      associated higher concurrency of sexual partners may contribute to racial
      disparities in STI rates.

PMID- 11964935
TI  - Is vaginal douching associated with preterm delivery?
AB  - BACKGROUND: To examine the hypothesized association between vaginal douching and
      preterm delivery, we conducted a study among women in a managed care organization
      in Atlanta, GA. METHODS: We drew a stratified random sample of 262 preterm (20-36
      weeks' gestation) and 804 term deliveries that occurred between January 1996 and
      April 1997. Data were collected from telephone interviews and medical records. We
      used proportional hazards regression to compute gestation-specific conditional
      probabilities of delivery. The risk of preterm delivery associated with douching
      was examined, adjusted for potential confounders. RESULTS: Douching during
      pregnancy increased the overall risk of preterm delivery (hazard ratio = 1.9, 95%
      confidence interval = 1.0-3.7). CONCLUSIONS: Further research to clarify the
      relation between douching and preterm delivery should pay particular attention to
      the role of vaginal infections.

PMID- 11964936
TI  - Do children of long-lived parents age more successfully?
AB  - BACKGROUND: Long-lived individuals are rare and may be selected in part for the
      genetic factors that promote successful aging. The children of long-lived parents
      may therefore age more successfully than the children of short-lived parents.
      METHODS: We used three major cross-sectional population-based surveys to study
      the association of parental longevity with successful aging in offspring. The
      measures of aging were hand-grip strength, cognitive performance (Mini Mental
      State Examination and a cognitive composite score), self-reported diseases, and
      self-rated health. RESULTS: For every additional 10 years the parents lived,
      their children's grip strength increased by 0.32 kg (95% CI = 0.00-0.63), Mini
      Mental State Examination score by 0.20 points (95% CI = 0.03-0.37), and cognitive
      composite score by 0.24 points (95% CI = 0.07-0.40). A 10-year increment of
      parental life was associated with a reduction by approximately 0.20 in the
      adjusted odds ratio for their children having each of the following conditions:
      diabetes; hypertension; ischemic heart disease; heart failure; stroke; or fair,
      poor, or very poor self-rated health. Almost all the effects were seen solely in
      the cohort of 70+-year-olds, but not among middle-aged or nonagenarian subjects.
      CONCLUSIONS: Parental life span is positively associated with the children's
      physical and cognitive functioning and avoidance of some of the common chronic
      diseases. However, the effects are small and are seen among offspring who are
      elderly, but not among the middle-aged or the oldest old.

PMID- 11964937
TI  - Chronic disease score as a predictor of hospitalization.
AB  - BACKGROUND: The Chronic Disease Score is a risk-adjustment metric based on age,
      gender, and history of dispensed drugs. We compared four versions of the score
      for their ability to predict hospitalization among members of eight health
      maintenance organizations nationwide. METHODS: The study included 29,247 women
      age 45 years and older. Logistic regression models were constructed using rank
      quintile and rank decile indicators for each of four scores as predictors of
      hospitalization during the year after 1 October 1995. Discrimination and model
      fit were compared using several model properties including the C statistic and
      the odds ratio comparing highest with lowest quantiles. RESULTS: All Chronic
      Disease Score versions performed similarly, with the version that predicts total
      healthcare cost, proposed by Clark et al. (Med Care 1995;33:783-795), performing
      somewhat better than the other three. The overall risk of hospitalization was
      12%. Individuals with higher quantile ranks had a higher risk of hospitalization.
      Among the Chronic Disease Score versions, the risk of hospitalization ranged from
      4% for the lowest decile to 27-29% for the highest decile. Odds ratios comparing
      the highest with the lowest deciles ranged from 8.9 to 10.2. CONCLUSIONS: The
      Chronic Disease Score predicts hospitalization and therefore may be a useful
      indicator of baseline comorbidity for control of confounding.

PMID- 11964938
TI  - Impact of missing data due to selective dropouts in cohort studies and clinical
      trials.
AB  - BACKGROUND: Many cohort studies and clinical trials use repeated measurements of
      laboratory markers to track disease progression and to evaluate new therapies. A
      major problem in the analysis of such studies is that marker data are censored in
      some patients owing to withdrawal, loss to follow-up, or death. The objective of
      this paper is to evaluate the impact of selective dropouts attributable to death
      or disease progression on the estimates of marker change among different groups.
      METHODS: Data on CD4 cell count in human immunodeficiency virus 1-infected
      individuals from a clinical trial and a cohort study are used to illustrate this
      problem and a possible solution. Simulation studies are also presented. RESULTS:
      When the rate of dropout is greater in subjects whose marker status is declining
      rapidly, commonly used methods, like random effects models, that ignore
      informative dropouts lead to overoptimistic statements about the marker trends in
      all compared groups, because subjects with steeper marker drops tend to have
      shorter follow-up times and hence are weighted less in the estimation of the
      group rate of the average marker decline. CONCLUSIONS: The potential biases
      attributable to incomplete data require greater recognition in longitudinal
      studies. Sensitivity analyses to assess the effect of dropouts are important.

PMID- 11964939
TI  - Brain tumors and salivary gland cancers among cellular telephone users.
AB  - BACKGROUND: Possible risk of cancer associated with use of cellular telephones
      has lately been a subject of public debate. METHODS: We conducted a register
      based, case-control study on cellular phone use and cancer. The study subjects
      were all cases of brain tumor (N = 398) and salivary gland cancer (N = 34)
      diagnosed in Finland in 1996, with five controls per case. RESULTS: Cellular
      phone use was not associated with brain tumors or salivary gland cancers overall,
      but there was a weak association between gliomas and analog cellular phones.
      CONCLUSIONS: A register-based approach has limited value in risk assessment of
      cellular phone use owing to lack of information on exposure.

PMID- 11964940
TI  - Joint effects of family history and adult life dietary risk factors on colorectal
      cancer risk.
AB  - BACKGROUND: We analyzed the joint effects of family history of colorectal cancer
      and adult life dietary risk factors on colorectal cancer risk. METHODS: We used
      data from a case-control study conducted in northern Italy between 1985 and 1992,
      including 1584 cases with colorectal cancer and 2879 controls. We created an
      adult life dietary risk factor score. RESULTS: Among subjects with family history
      of colorectal cancer, those in the lowest risk score tertile were not at elevated
      risk of colorectal cancer (odds ratio = 1.2; 95% confidence interval = 0.7-2.1),
      whereas those in the highest score tertile were at increased risk (odds ratio =
      5.5; 95% confidence interval = 3.5-8.7). CONCLUSIONS: These findings indicate
      that the expression of familial susceptibility can be substantially modified by
      adult life risk factors.

PMID- 11964941
TI  - The urban spread of visceral leishmaniasis: clues from spatial analysis.
AB  - BACKGROUND: The pattern of spread of visceral leishmaniasis in Brazilian cities
      is poorly understood. METHODS: We used geographic information systems and spatial
      statistics to evaluate the distribution of 1061 cases of visceral leishmaniasis
      in Teresina, Brazil, in 1993 through 1996. RESULTS: A locally weighted (LOESS)
      regression model, which was fit as a smoothed function of spatial coordinates,
      demonstrated large-scale variation, with high incidence rates in peripheral
      neighborhoods that bordered forest land and pastures. Moran's I indicated small
      scale variation and clustering up to 300 m, roughly the flight range of the sand
      fly vector. CONCLUSIONS: Spatial analytical techniques can identify high-risk
      areas for targeting control interventions.

PMID- 11964943
TI  - First trimester ultrasound scans and left-handedness.

PMID- 11964944
TI  - Specificity of an association.

PMID- 11964945
TI  - Magnetic fields and miscarriage.

PMID- 11964946
TI  - Transition of the patient with inflammatory bowel disease from pediatric to adult
      care: recommendations of the North American Society for Pediatric
      Gastroenterology, Hepatology and Nutrition.

PMID- 11964947
TI  - Regulation of intestinal epithelial cell apoptosis and the pathogenesis of
      inflammatory bowel disorders.

PMID- 11964948
TI  - Investigating esophageal reflux with the intraluminal impedance technique.

PMID- 11964949
TI  - Gastroesophageal reflux and supraesophageal complications: really true or
      ballyhoo?

PMID- 11964950
TI  - Helicobacter pylori and nonulcer dyspepsia: is there a relation?

PMID- 11964951
TI  - Prolonged esophageal pH monitoring in the evaluation of gastroesophageal reflux
      in children with chronic tubotympanal disorders.
AB  - BACKGROUND: Children with ear, nose and throat disorders are believed to have a
      high incidence of pathologic gastroesophageal reflux (GER). This study was
      designed to establish the frequency and ratio of pathologic GER in the
      development of chronic tubotympanal disorders. METHODS: Twenty-seven children
      with chronic tubotympanal disorders (mean age, 2 to 13 years; average age, 6.8
      years) underwent 24-hour continuous pH monitoring. Fourteen of the examined
      patients had secretory otitis, whereas 13 patients had recurrent otitis. From
      each 24-hour pH monitoring, 12-hour daytime and nighttime periods were selected.
      Eleven patients were tested using simultaneous dual pH monitoring (distal and
      proximal pH monitoring). RESULTS: Fifteen (55.6%) of 27 patients had pathologic
      GER. The authors did not find a relation between pathologic GER and different
      types of ear disorders. Daytime pH monitoring yielded significantly more episodes
      of reflux than did nighttime monitoring. The reflux index was substantially
      higher during the day. In the current study, distal pH monitoring showed that 6
      of 11 patients had pathologic GER, whereas proximal pH monitoring showed that
      only only 3 of 11 patients had pathologic GER. CONCLUSIONS: The authors recommend
      that a pH study be performed in children with chronic tubotympanal disorders when
      standard treatment is ineffective. The method of choice for the diagnosis of
      pathologic GER in patients with chronic tubotympanal disorders should be pH
      monitoring of the esophagus and throat.

PMID- 11964952
TI  - Treatment of Helicobacter pylori gastritis improves dyspeptic symptoms in
      children.
AB  - BACKGROUND: In adults, the treatment of Helicobacter pylori infection is only
      recommended for patients with active gastric or duodenal ulcers. It is not known
      whether similar guidelines can be applied to children because the prevalence of
      peptic ulcer disease in childhood is estimated to be much lower than in adults.
      The purpose of this study was to determine whether treatment of H. pylori
      gastritis would improve symptoms of dyspepsia in children. METHODS: Sixteen
      patients (5 boys, 11 girls) aged 14 +/- 1.2 years who had symptoms of dyspepsia
      were evaluated using upper gastrointestinal endoscopy with biopsies to establish
      the diagnosis of H. pylori gastritis. They were treated for 2 weeks with
      clarithromycin, amoxicillin, and a proton pump inhibitor. Dyspepsia symptoms were
      evaluated by a questionnaire before and after treatment of the infection. The
      effect of H. pylori treatment on the total symptom score was analyzed with use of
      the Student t test. Values are presented as mean +/- SEM. RESULTS: All patients
      had antral nodularity and chronic active gastritis with spiral-shaped organisms
      but no evidence of peptic ulcer disease. Mean total symptom score decreased
      significantly at 2 to 4 weeks after treatment (12.6 +/- 0.9 vs. 2.1 +/- 0.5 P <
      0.001), and it remained low (2.9 +/- 0.7) at follow-up 9.7 +/- 1.4 months (range,
      2-24 months later). CONCLUSION: These results suggest that the treatment of H.
      pylori gastritis can improve dyspeptic symptoms in children.

PMID- 11964953
TI  - Total dose intravenous infusion of iron dextran for iron-deficiency anemia in
      children with inflammatory bowel disease.
AB  - BACKGROUND: Iron-deficiency anemia is a frequent complication in children with
      inflammatory bowel disease (IBD). Parenteral iron therapy is rarely prescribed
      because of concern about potential side effects. The aim of this study was to
      retrospectively evaluate the safety and efficacy of total dose intravenous (TDI)
      iron therapy. METHODS: Charts of all the pediatric patients with IBD who received
      TDI iron therapy between February of 1994 and February of 2000 were reviewed.
      RESULTS: Seventy patients (20 with ulcerative colitis and 50 with Crohn disease)
      received a total of 119 TDI iron dextran infusions. Thirty-four patients
      qualified for the efficacy analysis. The average increase in hemoglobin
      concentration was 2.9 g/dL, (P < 0.0001). Eleven immediate hypersensitivity
      reactions developed in 10 patients (9% of the total number of infusions). None of
      the reactions was life threatening and none required hospitalization.
      CONCLUSIONS: Total dose intravenous infusion of iron dextran, when appropriately
      used, is a safe and potentially efficacious treatment for children with
      inflammatory bowel disease and iron deficiency anemia who are unresponsive to or
      noncompliant with oral iron therapy.

PMID- 11964954
TI  - Clinical quiz. Esophageal duplication.

PMID- 11964957
TI  - Effect of renutrition on natural and cell-mediated immune response in infants
      with severe malnutrition.
AB  - BACKGROUND: The purpose of this study was to evaluate whether a 4-week
      nutritional recovery period with a starting infant formula and 3.35 kJ/mL energy
      density would favorably affect the natural and cell-mediated immune response in
      infants with severe and primary protein-energy malnutrition. METHODOLOGY: The
      study included 12 severely malnourished infants, 3 to 18 months of age. For 2
      weeks, infants were fed a starting infant formula, with energy density increased
      to 0.8 kcal/mL, through a nasogastric tube. Infants were fed "ad libitum" for 2
      more weeks. On the fifth day, 837 kJ/kg and 4 g/kg protein were given daily. At
      the beginning and at the end of the 4-week period, weight, length, phagocytosis,
      microbicidal activity, chemotaxis, and cell proliferation indices were measured.
      Null hypothesis was rejected with a paired t test and a P value less than 0.05.
      RESULTS: After the 4-week period of nutritional recovery, the weight and length
      indicators and the four immunologic assays showed significant increase (P <
      0.005). CONCLUSION: The study demonstrated that a 4-week nutritional recovery
      period with a starting infant formula and 0.8 kcal/mL energy density favorably
      affected the natural and cell-mediated immune response in infants with severe
      protein-energy malnutrition.

PMID- 11964956
TI  - Dosage-related bifidogenic effects of galacto- and fructooligosaccharides in
      formula-fed term infants.
AB  - BACKGROUND: Human milk oligosaccharides have been shown to stimulate selectively
      the growth of Bifidobacteria and Lactobacilli in the intestine. In this study,
      the bifidogenic effect of an experimental prebiotic oligosaccharide mixture
      consisting of low-molecular-weight galactooligosaccharides and high-molecular
      weight fructooligosaccharides was analyzed in 90 term infants. METHODS: Two test
      formulas were supplemented with either 0.4 g/dL or with 0.8 g/dL
      oligosaccharides. In the control formula, maltodextrin was used as placebo. At
      study day 1 and study day 28, the fecal species, colony forming units (cfu) and
      pH were measured and stool characteristics, growth, and side effects were
      recorded. RESULTS: At study day 1, the median number of Bifidobacteria did not
      differ among the groups (0.4 g/dL group, mean [interquartile range] 8.5 [1.9]
      cfu/g; 0.8 g/dL group, 7.7 [6.1] cfu/g; and the placebo group, 8.8 [6.1] cfu/g)
      (figures in square brackets are interquartile range). At the end of the 28-day
      feeding period, the number of Bifidobacteria was significantly increased for both
      groups receiving supplemented formulas (the 0.4 g/dL group, 9.3 [4.9] cfu/g; the
      0.8 g/dL group, 9.7 [0.8] cfu/g) versus the placebo group (7.2 [4.9] cfu/g, P <
      0.001). This effect was dose dependent (0.4 g/dL versus 0.8 g/dL, P < 0.01). The
      number of Lactobacilli also increased significantly in both groups fed the
      supplemented formulas (versus placebo, P < 0.001), but there was no statistically
      significant difference between the group fed formula with 0.4 g/dL
      oligosaccharides and the group fed formula with 0.8 g/dL oligosaccharides. The
      dosage of supplement significantly influenced the change in fecal pH (P < 0.05)
      (placebo, pH 5.5-6.1; 0.4 g/dL formula, pH 5.48-5.44; 0.8 g/dL formula, pH 5.54
      5.19). Slight changes in the stool frequency resulted in a significant difference
      between the placebo group and the group fed the 0.8 g/dL formula at day 28 (P <
      0.01). Supplementation had a significant dose-dependent influence on stool
      consistency (0.8 g/dL versus placebo, P < 0.0001; 0.8 g/dL versus 0.4 g/dL, P <
      0.01). Supplementation had no influence on the incidence of side effects (crying,
      regurgitation, vomiting) or growth. CONCLUSIONS: These data indicate that
      supplementation of a term infant's formula with a mixture of galacto- and
      fructooligosaccharides has a dose-dependent stimulating effect on the growth of
      Bifidobacteria and Lactobacilli in the intestine and results in softer stool with
      increasing dosage of supplementation.

PMID- 11964958
TI  - Increased rectal nitric oxide in children with active inflammatory bowel disease.
AB  - BACKGROUND: Luminal nitric oxide increases in ulcerative colitis and Crohn
      disease. The authors have previously used a minimally invasive method to
      demonstrate increased luminal nitric oxide in ulcerative colitis and Crohn
      disease of the colon. The aim of the current study was to determine whether this
      method could be applied to identify inflammatory activity in ulcerative colitis
      and Crohn disease in children. METHODS: Thirty-six children (18 of whom had
      active disease) with inflammatory bowel disease localized to the colon were
      studied. The control group comprised 12 healthy children. To measure nitric
      oxide, a silicon catheter with an inflatable balloon was inserted into the rectum
      and inflated with 10 mL of nitric oxide-free air. After a 10-minute incubation
      time, the air was withdrawn and nitric oxide concentrations were immediately
      analyzed using a chemiluminescence technique. RESULTS: Children with active
      ulcerative colitis and Crohn disease of the colon had greatly increased luminal
      nitric oxide concentrations in the rectum (8,840 +/- 5,120 and 15,170 +/- 4,757
      parts per billion [ppb], respectively) compared with controls (77 +/- 17 ppb) (P
      < 0.001). Children with nonactive ulcerative colitis or Crohn disease displayed
      low concentrations of rectal nitric oxide (356 +/- 110 and 188 +/- 55 ppb,
      respectively), which was not different from that of healthy controls. CONCLUSION:
      Rectal nitric oxide measurement is a feasible and useful method for monitoring
      disease activity in inflammatory bowel disease, especially in children.

PMID- 11964959
TI  - Infliximab as a novel therapy for pediatric ulcerative colitis.
AB  - OBJECTIVES: The role of infliximab (anti-tumor necrosis factor alpha antibody)
      therapy in ulcerative colitis (UC) is not well defined. There are only two
      reports published describing its use in UC. The authors describe their experience
      with open-label use of infliximab in children with moderate to severe UC.
      METHODS: The authors collected data on all consecutive pediatric patients with UC
      who received infliximab at The Children's Hospital of Philadelphia until July
      2001. The primary measured outcome was clinical response at 2 days and 2 weeks
      after infliximab infusion, as measured by the Lichtiger colitis activity index
      (LCAI) score and the Physician Global Assessment (PGA). Tolerance of the
      infusions and adverse events were recorded. RESULTS: Nine patients qualified for
      clinical response analysis. The median Lichtiger colitis activity index score
      decreased from 11 before the infusion to 1 at 2 days and 2 weeks after the
      infusion, respectively (P = 0.01 for 2 days and 2 weeks). Seven of nine (77%)
      patients had decreased activity of their disease measured by the Physician Global
      Assessment. Corticosteroid therapy was discontinued in six (66%) patients. An
      infusion reaction developed (generalized pruritus and facial flushing) in two
      patients and an elevated anti-nuclear antibody (ANA) titer of 1:1280 developed in
      one patient. CONCLUSION: Infliximab is associated with short-term clinical
      improvement in children and adolescents with moderate to severe UC.

PMID- 11964961
TI  - Celiac disease--associated vertigo and nystagmus.

PMID- 11964962
TI  - Gastric inflammatory myofibroblastic tumors in children: an unpredictable course.

PMID- 11964960
TI  - Autoimmune enteropathy in a child: response to infliximab therapy.

PMID- 11964963
TI  - Pig-bel (necrotizing enteritis) in the Americas?

PMID- 11964964
TI  - Age-dependent variations in fecal calprotectin concentrations in children.

PMID- 11964968
TI  - CFCI gene mutation and biliary atresia with polysplenia syndrome.

PMID- 11964966
TI  - Eosinophilic esophagitis--is it in the air?

PMID- 11964969
TI  - Neurovascular free-muscle transfer to treat facial paralysis associated with
      hemifacial microsomia.
AB  - Despite the wide spectrum of hemifacial microsomia manifestations, treatment
      mainly focuses on mandible and ear abnormalities, rather than on facial
      paralysis. In fact, the surgical treatment of facial paralysis associated with
      hemifacial microsomia is quite underdeveloped, because the degree of paralysis is
      frequently incomplete or partial. Timing and type of surgery are also difficult
      to determine. Neurovascular free-muscle transfer is now a standard procedure for
      the dynamic smile reconstruction of longstanding facial paralysis. This type of
      strategy has considerable potential in the treatment of facial paralysis in
      patients with hemifacial microsomia. We present here our experience with
      neurovascular free-muscle transfer for smile reconstruction in eight patients
      with facial paralysis associated with hemifacial microsomia. The age of the
      patients at the time of surgery ranged from 7 to 28 years old, (average, 13.9
      years). Six were male patients and two were female patients. The two-stage method
      combining gracilis muscle transfer with cross-face nerve grafting was performed
      in three patients, whereas the one-stage transfer of the latissimus dorsi muscle
      was performed in five. To construct a natural or near-natural smile, the muscles
      were transferred into the paralyzed cheek in all except one patient, in whom the
      latissimus dorsi muscle was transferred into the sublabial area to reconstruct a
      paralyzed lower lip. A dermal flap segment vascularized with perforating vessels
      from the latissimus dorsi muscle was simultaneously inserted into the
      underdeveloped cheek for soft-tissue augmentation in this patient. Muscle
      contraction was evident in all patients between 4 and 8 months after muscle
      transfer. Our present series revealed that neurovascular free-muscle transfer is
      a good option not only for smile reconstruction but also for restoration of the
      facial contours of patients with hemifacial microsomia. Compared with the two
      stage method combining gracilis muscle transfer with cross-face nerve grafting,
      the one-stage method using the latissimus dorsi muscle has some advantages,
      including a one-stage operation, a shorter recovery period, and the absence of
      sequelae that occur after harvesting a sural nerve.

PMID- 11964970
TI  - Netting operation to control neurofibroma of the face.
AB  - When neurofibroma involves the face, it can lead to a most disfiguring,
      destructive, and debilitating condition. Because of the unique aesthetic and
      functional properties of the face, the surgeon might hesitate to remove all of
      the involved soft tissues and facial nerves in a radical procedure. Involvement
      of the craniofacial skeleton makes the treatment more difficult and complex. The
      treatment usually consists of excising the symptomatic lesion, and often these
      lesions are incompletely corrected. Regrowth after partial excision is frequent
      and leads to recurrence of deformity. The force of gravity plays a major role in
      the appearance of deformity, leading to facial tissue drooping and bulging as the
      mass grows and gains weight. The aim of this operation was to contain the
      residual mass after excision within a tight net against the force of gravity,
      thus limiting and preventing drooping or bulging of the facial soft tissue while
      preserving muscles and nerves associated with facial expression.
      Polytetrafluoroethylene (Teflon) mesh, used as a net, was evaluated as a
      replacement material for subcutaneous tissue and a substitute for superficial
      fascia destroyed by tumor infiltration. The mesh was suspended in the superior
      posterior direction, capturing the residual mass like a net capturing fish. From
      1989 to 1999, a total of eight patients underwent the netting procedure after
      partial excision of neurofibroma of the face. The follow-up period was 3 to 10
      years. The use of Teflon mesh proved to be compatible with the surrounding
      tissue, endurable at follow-up, and consistent with expectations. Follow-up
      computed tomographic scans revealed no further visible tumor growth, and the area
      was contained under the mesh net with satisfactory postoperative facial contour.
      The advantages of this procedure are the avoidance of radical excision of facial
      soft tissue, preservation of remnant facial expression, and prevention of
      progression of facial dysmorphism.

PMID- 11964974
TI  - Usefulness of a first transferred free flap vascular pedicle for secondary
      microvascular reconstruction in the head and neck.
AB  - The authors found that a previously transferred free flap vascular pedicle,
      distal to the first microvascular anastomosis, can be used as a recipient vessel
      for an additional free flap transfer. Free flap transfers were performed by using
      the standard procedure in patients with head and neck cancer. The mean age of the
      patients was 62 years. Five patients were men and three were women. A second free
      flap was transferred for secondary primary head and neck cancer in two cases,
      facial deformity in two cases, osteomyelitis of the skull in two cases, recurrent
      cancer in one case, and exposure of a mandibular reconstruction plate in one
      case. The interval between the two operations was from 4 months to 12 years
      (median, 21 months). All secondary free flaps were performed successfully. In two
      cases, the external jugular vein proximal to the previously anastomosed site was
      used for venous drainage. In another case, additional venous anastomosis was
      performed for flap congestion. It became clear that a previously transferred free
      flap vascular pedicle could be used as a recipient vessel for microvascular
      anastomosis. This is an excellent procedure for additional free flap transfers.

PMID- 11964972
TI  - Functional reconstruction of maxilla with free latissimus dorsi-scapular
      osteomusculocutaneous flap.
AB  - Restoration of oral and nasal function together with facial appearance is still
      challenging in maxillary reconstruction. Use of a composite flap transfer merely
      to fill the defect results in unsatisfactory functional and aesthetic outcomes.
      The authors present a reconstructive procedure for complex maxillary defects
      using the latissimus dorsi-scapular rib osteomusculocutaneous flap. Some
      modifications for the reconstruction of the nasal cavity and the hard palate
      contributed to excellent postoperative functions. Five cases of extended
      maxillary defect were reconstructed using a novel procedure between February of
      1997 and October of 2000. The hard palate was reconstructed with a vascularized
      scapular angle. The infraorbital rim was reconstructed with a vascularized rib if
      it was required. A prop bone graft, replacing the zygomatic buttress, was added
      between the infraorbital rim and the hard palate. The latissimus dorsi muscle
      flap, which was supported by a skeletal framework and obliterated the remaining
      cavities around the bone grafts, was left exposed into the nasal cavity, and an 8
      French (no. 10) nasal airway tube was placed as a stent in the nasal meatus for 3
      weeks after surgery. A skin graft was applied on the scapular angle to
      reconstruct the oral side of the hard palate. If required, facial skin defect was
      repaired with a latissimus dorsi musculocutaneous flap or scapular flap. No major
      complications at the recipient or the donor sites occurred postoperatively in any
      of the five cases. In cases in which the eyeballs were preserved, almost normal
      facial appearance was obtained and an orbital extirpation case showed an
      acceptable postoperative appearance. All five patients returned to an
      unrestricted diet and their speech was assessed as normal by a speech test. Nasal
      breathing through the re-epithelialized meatus was possible in all cases. The
      reconstructed nasal cavity was maintained for more than 6 months in all cases and
      for more than 2 years in one early case. Rhinometry demonstrated normal function,
      and histologic findings of the re-epithelialized mucosa over the muscle flap in
      the nasal cavity revealed a nearly normal architecture. This technique simplifies
      the reconstructive procedure of massive maxillary defects, including those in the
      lateral wall of the nasal cavity. It also improves the postoperative oral and
      nasal functions of the patients.

PMID- 11964975
TI  - Intraarterial chemotherapy: the effects on free-tissue transfer.
AB  - Multimodal therapy including intraarterial chemotherapy is recognized as state-of
      the art therapy for soft-tissue cancer. Multimodal therapy often involves
      regional limb perfusion followed by sarcoma surgery with reconstruction of the
      resulting defect. This study was performed in an effort to evaluate the potential
      of free flap reconstruction after intraarterial therapy. A retrospective chart
      review of 52 patients who had undergone limb perfusion between 1988 and 1998 at
      the University of Texas M. D. Anderson Cancer Center and the Division of Plastic
      Surgery, University of Bochum, Germany, identified 16 patients who had undergone
      intraarterial limb perfusion that was then followed by surgical resection and
      free flap reconstruction. There were seven women and nine men, with an average
      age of 37.9 years. All sixteen patients had received preoperative adjuvant
      systemic chemotherapy. Reconstruction of the lower extremity was performed most
      commonly with rectus abdominis and latissimus dorsi free flaps. All vessels used
      for donor recipient anastomosis had been previously perfused. A vein graft was
      used in one case. Split-thickness skin grafting over the free flaps was used in
      four cases. The average length of hospitalization was 21.75 days, with an average
      follow-up of 20 months. No flap loss or infection was observed. Two flaps
      demonstrated partial edge necrosis. Three patients developed partial split
      thickness skin graft loss and one developed a seroma that required no treatment.
      A draining sinus tract required resection in one patient. The overall flap
      success rate was 100 percent, with no flap failures. The overall surgical outcome
      was considered to be good in 12 patients on the basis of improved function and
      ambulation, and fair in four who had limitations in function and/or ambulation on
      the basis of both the patient self-evaluation and the physical therapy
      evaluation. Seven patients had recurrence of their disease. The overall mean
      survival time after surgery was 20.6 months. Currently, 10 patients are alive and
      six have died from their disease. The results of this study indicate that
      preoperative intraarterial chemotherapy does not significantly increase the risk
      of immediate free flap complications. Although our numbers are small, we believe
      that there is no clinical evidence justifying hesitation or refusal of free flap
      reconstruction after limb perfusion and intraarterial chemotherapy. Routine care
      in vessel selection and microsurgical technique should be performed to maximize
      favorable outcomes. Vessels should be inspected for their suitability before
      undertaking any free flap reconstruction.

PMID- 11964976
TI  - Facial fractures from dog bite injuries.
AB  - Dog bites are commonly associated with soft-tissue injury to the face but rarely
      result in facial fractures. This article reports six new cases of facial
      fractures associated with dog bites and reviews additional cases reported in the
      literature. The demographics of the patients attacked, the location of facial
      fractures, and the characteristics of associated soft-tissue injuries or
      complications developing from the dog bite are described. With six new cases and
      10 from the literature, this article reviewed a total of 16 cases involving 27
      facial fractures. Eighty-seven percent of the cases involved children less than
      16 years of age. The periorbital or nasal bones were involved in 69 percent of
      the cases. Lacerations were the most frequently associated soft-tissue injury.
      Additional injuries included facial nerve damage, lacrimal duct damage requiring
      stenting and reconstruction, ptosis from levator transection, and blood loss
      requiring transfusion. Although facial fractures are not commonly considered to
      be associated with dog bite injuries, the index of suspicion for a fracture
      should be raised when the injury occurs in a child, particularly when injury
      occurs near the orbit, nose, and cheek.

PMID- 11964977
TI  - Early excision and grafting of face and neck burns in patients over 20 years.
AB  - Although excision and grafting of burns has become common and standard, many
      surgeons have been reluctant to excise and graft face burns. In fact, we could
      find photographic results at 1 year after grafting of only eight patients in the
      English literature. We began excision and grafting of face burns in 1979 and
      presented our first 16 patients in 1986 in this journal. With encouragement from
      Janzekovic and Jackson, we continued and have now used essentially the same
      procedure for more than 20 years in approximately 100 patients and, from this
      large series, are able to present outcomes. From January of 1979 to May of 1999,
      we performed excision and grafting on 91 patients with deep face burns. Data were
      recorded and 35-mm photographs were obtained throughout the 20-year period. We
      reviewed that database and the slide files of these patients. We found 45
      patients with complete photographic sets including 1-year follow-up. Since, in
      our opinion, there is no useful, objective measure of appearance, we decided to
      simply publish all 45 sets of complete photographs, permitting the reader to
      subjectively form an opinion of the outcome of this procedure. The results are
      all shown as "full" face burns and two "partial" face burns. We continue to
      believe that early excision and grafting is indicated for face burns that will
      not heal within 3 weeks and that the procedure yields results that permit the
      burn victims to return to society and minimizes the time off work or out of
      school.

PMID- 11964978
TI  - Successful treatment of 19 consecutive groin lymphoceles with the assistance of
      intraoperative lymphatic mapping.
AB  - Postoperative groin lymphoceles that fail to resolve spontaneously or with
      interventional therapy present a formidable problem that is associated with a
      high degree of morbidity. Numerous interventional methods and operative
      techniques have been described to treat these fluid collections, yet recurrence
      rates remain high. The use of lymphatic mapping has gained widespread use in the
      treatment of cutaneous malignancies and breast cancer and has been proven
      effective in delineating the course of lymphatic channels. We present here a
      series of 17 consecutive patients with 19 problematic groin lymphoceles who were
      treated with the assistance of intraoperative lymphatic mapping using isosulfan
      blue dye. To date there have been no recurrences and minimal morbidity associated
      with the technique and prescribed postoperative treatment regimen.

PMID- 11964979
TI  - The relative roles of aggressive wound care versus revascularization in salvage
      of the threatened lower extremity in the renal failure diabetic patient.
AB  - Current literature indicates poor survival and limb salvage rates in renal
      failure diabetic patients who present with ulcerated or gangrenous lower
      extremities. Even in those limbs that were successfully revascularized, the
      amputation rate was as high as 37 percent. This has led some to advocate
      immediate amputation when treating the threatened limb of a renal failure
      diabetic patient. The authors reviewed all renal failure diabetic patients in
      their wound registry to determine whether such pessimism was warranted. The
      authors then analyzed the relative roles of revascularization and aggressive
      wound care on long-term limb salvage. Forty-five consecutive renal failure
      diabetic patients with 71 wounds in 54 limbs were identified. Twenty-seven
      patients had chronic renal insufficiency, 15 patients had end-stage renal
      disease, and three patients received kidney transplants. The revascularization
      procedures (46 percent of all limbs) included angioplasty, femoral-popliteal,
      femoral-distal, and popliteal-distal bypasses. Forty-three amputations in
      combination with 67 soft-tissue repairs (delayed primary wound closure, skin
      grafts, local flaps, pedicled flaps, and free flaps) were necessary to close the
      defects. After a mean follow-up of over 3 years, the data indicate that 79
      percent of wounds healed, 89 percent of all limbs were salvaged, and 49 percent
      of patients survived. Revascularization improved the threatened limb's salvage
      rate from negligible to a level similar to that of the adequately vascularized
      limb. Fifteen out of 71 wounds did not heal because of the patient's early
      postoperative death, ischemia not amenable to revascularization, or
      noncompliance. Six below-knee amputations were performed (one despite a patent
      bypass and five in adequately vascularized patients). The average time for wounds
      to heal in the revascularized patients was 79 days versus 71 days in adequately
      vascularized patients. There was an overall 43 percent complication rate. Of the
      patients who were alive after the 3-year follow-up, 73 percent were independently
      ambulating, whereas 27 percent were bound to wheelchair or bed. Eighty-two
      percent of patients were very satisfied with the salvage attempt, 18 percent were
      moderately satisfied, and all patients said they would go through the process
      again. The authors believe that salvaging the threatened extremity in the renal
      failure diabetic patient is justified whether or not the limb requires
      revascularization. Revascularization improved the limb salvage rate, patient
      survival, and days for wounds to heal to a level comparable to that of the
      adequately vascularized limb. The key to subsequently achieving high salvage
      rates is the quality of perioperative wound care (e.g., serial debridements,
      antibiotics, dressings) and the timing and selection of appropriate soft-tissue
      coverage.

PMID- 11964981
TI  - Treatment of Kienbock's disease with capitohamate arthrodesis: pain relief with
      minimal morbidity.
AB  - Despite the large number of procedures available for treatment of Kienbock's
      disease, no single method has emerged as being clearly superior. Ultimately, the
      goal of treatment must be the relief of pain and maintaining wrist range of
      motion. The authors' experience with 45 consecutive wrists that had undergone
      capitohamate fusion for treatment of Lichtman's stage 1, 2, or 3 Kienbock's
      disease is presented. Average follow-up was 32 months (range, 4 to 107 months).
      All arthrodeses healed with an average time to fusion of 1.9 months.
      Postoperatively, 93 percent of patients had either no pain or less pain than they
      had preoperatively, with preservation of wrist range of motion and improved grip
      strength (52 percent of normal preoperatively to 72 percent of normal
      postoperatively). The authors conclude that capitohamate arthrodesis relieves
      pain in 93 percent of patients with stage 1, 2, or 3 Kienbock's disease and is an
      effective treatment for this disease.

PMID- 11964982
TI  - Male perineogenital anatomy and clinical applications in genital reconstructions
      and male-to-female sex reassignment surgery.
AB  - To determine the possibility of providing alternative surgical techniques for
      male genital reconstruction and for male-to-female sex reassignment surgery, the
      authors undertook an anatomic investigation of the perineogenital region in male
      cadavers. Anatomic dissection was performed on 14 male adult human cadavers
      (fresh and formalin-preserved) studying the main afferent vessels to the anterior
      perineal region and their mean internal diameters: deep external pudendal artery
      (0.60 mm), superficial perineal artery (0.50 mm), and funicular artery (0.37 mm).
      We established their exact topography, together with vascular anatomic
      variations, main vascular anastomosis circuits (base of the penis, scrotal
      septum, and perineal fat and lateral spermatic-scrotal fascia), angiosomes,
      anatomy of the rectovesical septum cavity, and their "critical" key points of
      dissection. The authors discuss the clinical possibility of elevation of a "tree"
      of previously described paragenital-genital flaps including mainly those based on
      the terminal branches of the internal pudendal vascular system, the erectile
      tissue pedicled flaps, and finally, flaps of the external pudendal system. The
      authors indicate the concrete vascularization system for each flap.

PMID- 11964983
TI  - Efficacy of radioprotection in the prevention of radiation-induced craniofacial
      bone growth inhibition.
AB  - It has been reported that radiotherapy-induced craniofacial deformities can occur
      in 66 to 100 percent of survivors of childhood head and neck cancers. Recent
      interest in the effectiveness of radioprotectors in the protection of normal
      tissue against radiation injury led us to investigate a possible role of
      radioprotection in the prevention of radiation-induced craniofacial bone growth
      inhibition. Therefore, the objective of this study was to use the radioprotective
      agent amifostine (Ethyol, WR-2721) as a probe to determine the effectiveness of
      radioprotection in the prevention of radiation-induced craniofacial bone growth
      inhibition after single-dose orthovoltage radiation to the infant rabbit orbital
      zygomatic complex. Seven-week-old male New Zealand white rabbits were randomized
      into three groups (n = 10 each): group 1, 0 Gy (sham radiation); group 2, 35-Gy
      single-dose orthovoltage radiation; and group 3, 35-Gy single-dose orthovoltage
      radiation and amifostine (300 mg/kg intravenously, given 20 minutes before
      radiation). Serial radiographs and computed tomographic scans were obtained for
      cephalometric analysis, bone volume, and bone density measurements until skeletal
      maturity at 21 weeks. Significant (p < 0.05) reductions in orbital-zygomatic
      complex linear bone growth, bone volume, and bone density were observed after 35
      Gy radiation compared with nonirradiated controls. No significant differences
      were noted between groups in cephalometric analysis of the nontreated
      (nonirradiated) left orbital-zygomatic complex, indicating no crossover effect
      from the radiation beam. However, pretreatment with amifostine, 20 minutes before
      35-Gy radiation, resulted in significant (p < 0.05) preservation of linear bone
      growth, bone volume, and bone mineral density in the rabbit orbital-zygomatic
      complex compared with controls. This study demonstrated for the first time the
      effectiveness of a radioprotector in the prevention of radiation-induced
      craniofacial bone growth inhibition, and it paves the way for investigation into
      the pathogenic mechanism and prevention of radiotherapy-induced craniofacial
      deformities.

PMID- 11964985
TI  - Calvarial bone distraction with a contractile bioresorbable polymer.
AB  - The aim of the present study was to evaluate the possibility of mobilizing
      calvarial bone with a fully implantable and bioresorbable device. The animal
      model used was the New Zealand white rabbit (n = 12). An island bone flap
      attached to the dura mater was created in the parietal region and amalgam markers
      were placed in this bone flap and in the ipsilateral frontal bone. In one group
      of six rabbits (group 1), a specially processed contractile 70L/30D,L polylactic
      acid plate, 15 x 6 x 0.6 mm, was attached to the island flap by one extremity,
      and to the fixed ipsilateral frontal bone by the other. In group 2 (control), no
      plate was added. Bone marker movement was followed with serial radiography. In
      group 1, there was a progressive reduction in mean marker distance over the first
      48 hours, and stability thereafter. In group 2 (control), mean marker distance
      remained stable until the second postoperative week, after which time there was a
      slight increase until the end of the experimental period. At 4 weeks, the mean
      marker separation differed significantly between group 1 (mean, -3.62 mm; SD,
      0.79 mm) and group 2 (mean, 0.34 mm; SD, 0.14 mm; p <0.001). In conclusion, a
      totally implantable and bioresorbable device was successfully used to mobilize
      calvarial bone. Polymer contractility will likely constitute the basis of a new
      generation of bioresorbable distractors for use in craniofacial surgery.

PMID- 11964987
TI  - Effect of bioabsorbable osseous fixation materials on dura mater and brain
      tissue.
AB  - Bioabsorbable materials are frequently used in pediatric cranial surgery, but the
      effects of these materials on neural tissue are not known. The authors assessed
      the histologic alterations to dura mater and brain tissue associated with
      bioabsorbable plates. Fifteen Sprague-Dawley rats were given sham cranial
      surgery; an additional 30 underwent placement of 8 x 8-mm polylactic acid/poly
      glycolic acid plates. The rats were assessed weekly for neurologic or behavioral
      changes suggesting neural damage. A portion of each group was killed at 3, 6, and
      12 months for histologic analysis of cranium, dura mater, and brain tissue by
      standard hematoxylin and eosin stain. None of the animals showed any behavioral
      changes or neurologic deficits. The plates were gradually hydrolyzed over the
      study period, and all had disappeared by 12 months. The histologic examination
      showed fibrous encapsulation around the plates, accompanied by foreign body giant
      cell reaction and calcification. Focal gliosis, where evident, was mild and
      confined primarily to the superficial cortex of the brain beneath the plate. The
      infiltration of the dura mater and underlying brain parenchyma was negligible. In
      conclusion, the neurologic and histologic effect of bioabsorbable plates on
      neural tissue may be considered negligible in the early postoperative period.

PMID- 11964989
TI  - Early and late effects of ischemic preconditioning on microcirculation of
      skeletal muscle flaps.
AB  - The present study was designed to investigate the early and late effects of
      ischemic preconditioning on muscle flap perfusion and reperfusion-induced
      skeletal muscle damage. Thirty-six Sprague-Dawley rats were divided into six
      experimental groups of six animals each. The cremaster muscle flap model and the
      intravital microscopy system were used to observe microcirculatory changes
      associated with ischemia-reperfusion injury and ischemic preconditioning. In
      groups 1, 2, and 3, microcirculatory measurements were taken on the same day;
      however, in groups 4, 5, and 6, measurements were taken a day after surgery.
      Group 1 served as a control. The cremaster muscle was prepared as a tube flap,
      subjected to an hour of perfusion without ischemia. In group 2 (ischemic
      preconditioning + ischemia group), the cremaster muscle tube flap was subjected
      to 30 minutes of ischemia and 30 minutes of reperfusion, followed by 4 hours of
      total ischemia. In group 3 (ischemia alone), the flap was submitted to 4 hours of
      ischemia alone. In group 4 (control), the cremaster muscle flaps were dissected
      out, preserved in the subcutaneous tunnel, and submitted to 24 hours of perfusion
      only. In group 5 (ischemic preconditioning + 24 hours of perfusion + 4 hours of
      ischemia), the ischemic preconditioning protocol was followed by 24 hours of
      perfusion and 4 hours of ischemia. In group 6 (24 hours of perfusion + ischemia),
      the same protocol was used as in group 5 without ischemic preconditioning.
      Functional capillary perfusion, and the diameters of the arterioles of the first,
      second, and third order were significantly increased in the ischemic
      preconditioning group during the early period, but not after 24 hours of
      perfusion. No differences in the red blood cell velocities of arterioles of the
      first, second, or third order were found in either the early-effect or late
      effect groups. The numbers of rolling, adhering, and transmigrating leukocytes,
      however, were significantly lower in the ischemic preconditioning group at both
      early and late follow-up. Ischemic preconditioning of the skeletal muscle flap
      has both an early and a late protective effect against reperfusion injury.
      Ischemic preconditioning at the early interval significantly improves muscle flow
      hemodynamics of the flap and attenuates leukocyte-mediated reperfusion injury.
      After 24 hours of reperfusion, however, ischemic preconditioning failed to
      improve the flow hemodynamics of the flap, yet it still protected the skeletal
      muscle flap from leukocyte-mediated reperfusion injury.

PMID- 11964988
TI  - Improvement in burn wound infection and survival with antimicrobial peptide D2A21
      (Demegel).
AB  - Naturally occurring antimicrobial peptides have been discovered in both plants
      and animals. Many of these peptides demonstrate impaired activity or cytotoxicity
      when applied exogenously. Synthetically engineered antimicrobial peptides have
      been designed to increase potency and activity against bacteria and fungus yet
      remain noncytotoxic. The antimicrobial peptide D2A21 (Demegel) has already
      demonstrated significant activity in vitro against many common hospital
      pathogens. The purpose of this study was to evaluate the effects of D2A21 in an
      in vivo infected burn-wound model, examining both quantitative cultures of the
      wound and survival of the animal. Forty-four Wistar rats were subjected to a 23
      percent total body surface area scald burn. Pseudomonas aeruginosa was
      administered topically with 108 organisms and wounds were then evaluated at day
      1, 2, or 3 for eschar and subeschar muscle quantitative culture. The experimental
      group was treated daily with 1.5% topical D2A21. The control group was treated
      with control gel. A second group of Wistar rats (n = 14) were burned and given a
      107 inoculum of the same Pseudomonas and evaluated to 14 days for survival and
      weight changes. This group was subdivided into rats receiving either topical
      D2A21 or control base daily. The quantitative biopsy results demonstrated that
      D2A21-treated wounds had no bacterial growth in burn eschar at day 2 or 3,
      whereas control animals demonstrated growth at greater than 105 organisms by day
      2. Subeschar muscle cultures also demonstrated significantly less bacterial
      invasion compared with controls on each day tested. D2A21-treated animals had an
      85.7 percent survival compared with 0 percent survival in controls. Furthermore,
      the D2A21-treated groups demonstrated maintenance of body weights, whereas
      controls had significant weight loss with time. In conclusion, D2A21 demonstrates
      significant antibacterial activity against Pseudomonas, sterilizing burn eschar
      and decreasing subeschar bacterial load, allowing for a markedly significant
      improvement in survival in this infected burn-wound model.

PMID- 11964990
TI  - In vivo efficacy of antimicrobe-impregnated saline-filled silicone implants.
AB  - Bacterial colonization of mammary implants is a prelude to clinical infection and
      has been implicated in the etiology of capsular contracture. Antimicrobial
      impregnation of a variety of medical devices with the combination of minocycline
      and rifampin has recently emerged as a potentially effective method for
      preventing device colonization and device-related infection. The objective of
      this animal study was to examine in vivo the antimicrobial efficacy of
      minocycline/rifampin-impregnated, saline-filled silicone implants. A rabbit model
      of Staphylococcus aureus colonization and infection of subcutaneously placed
      implants was used. A total of 48 saline-filled silicone implants (24 antimicrobe
      impregnated and 24 control unimpregnated implants) were suspended in a 106 colony
      forming units/ml bacterial suspension of S. aureus for 30 minutes at room
      temperature, allowed to dry for 60 minutes, and then implanted subcutaneously in
      the back of 12 rabbits (two antimicrobe-impregnated and two control implants were
      placed in each rabbit). Rabbits were monitored daily, then killed either at 2
      weeks (10 rabbits) or at 4 weeks (two rabbits) and cultured. The antimicrobe
      impregnated implants were 12 times less likely to be colonized than control
      unimpregnated implants (two of 24 versus 23 of 24; p < 0.001), and they were a
      significantly less likely cause of implant-related infection (0 of 24 versus 22
      of 24; p < 0.001) and implant-related abscess (0 of 24 versus 21 of 24; p <
      0.001) than control implants. The minocycline/rifampin-impregnated implants
      routinely demonstrated zones of inhibition against S. aureus at the time of
      explantation. These results indicate that minocycline/rifampin-impregnated
      implants can significantly decrease the rate of bacterial colonization, implant
      related infection, and implant-related abscess. Antimicrobe-impregnated implants
      also have the potential of reducing the likelihood of capsular contracture.

PMID- 11964991
TI  - Temporary placement of defatted plantar heel skin in the calf and subsequent
      transfer to the heel using distally based sural artery flap as a carrier.

PMID- 11964992
TI  - Simultaneous reconstruction of the posterior pharyngeal wall and cervical spine
      with a free vascularized fibula osteocutaneous flap.

PMID- 11964993
TI  - Reconstruction of defects involving the middle third of the auricle with a full
      thickness conchal chondrocutaneous flap.

PMID- 11964995
TI  - Current surgical therapy for quadriplegia: functional electrical stimulation.

PMID- 11964994
TI  - Thinning of the thoracodorsal perforator-based cutaneous flap for axillary burn
      scar contracture.

PMID- 11964996
TI  - Correction of secondary deformities of the cleft lip nose.

PMID- 11964997
TI  - "I Like Your Eyes".

PMID- 11964998
TI  - A system for breast implant selection based on patient tissue characteristics and
      implant-soft tissue dynamics.
AB  - Primary breast augmentation patients have widely varying characteristics of their
      breast envelope, parenchyma, and adjacent tissues. When preoperative breast
      implant selection does not specifically address critical soft-tissue parameters
      individual to each patient, risks of complications increase. Complications that
      occur from failure to reconcile a patient's wishes for breast size with her
      individual tissue characteristics include skin stretch and thinning, ptosis,
      atrophy of parenchyma, implant edge or shell visibility, implant edge or shell
      palpability, visible traction rippling, "bottoming" deformities, and lateral
      implant displacement with widening of the intermammary distance. Previous
      dimensional systems address implant parenchyma base width relative to implant
      base width, but no published system adequately addresses or attempts to
      quantitate the third dimension, tissue stretch, that is critical to estimate
      amount of fill necessary in a wide range of breast and tissue types. This system
      addresses the tissue characteristics (T) of the envelope (E), the parenchyma (P),
      and the implant (I), and the dynamics (D) of implant and filler distribution that
      affect soft tissues. The acronym TEPID summarizes the key factors that determine
      aesthetic results and occurrence of problems and reoperations following breast
      augmentation. This simple, efficient, and clinically practical system focuses on
      only three tissue measurements to estimate implant volume required to fill each
      patient's existing breast envelope, on the basis of her individual tissue
      characteristics: base width of the parenchyma, anterior pull skin stretch, and
      areola- and/or nipple-to-inframammary-fold distance measured under maximal
      stretch. The surgeon then adjusts initial volume to address differences in degree
      of skin stretch (anterior pull skin stretch) and contribution of the patient's
      existing parenchyma to stretched envelope fill, and to address differences in
      implant dimensions and filler distribution dynamics. To base decisions of implant
      pocket location on quantifiable soft-tissue coverage thickness, the system
      measures soft-tissue pinch thickness of the upper pole and at the inframammary
      fold. Surgeon time required to measure, estimate, and make preoperative implant
      selection decisions is less than 5 minutes. This system evolved from compiling
      and reviewing measurements and results from 330 primary breast augmentations from
      1996 to 1999, including round and anatomic implant types with smooth shells and
      two different textured shells. The TEPID system was then used concurrently with
      the previous dimensional system for patient tissue evaluation and preoperative
      implant selection in 627 consecutive primary augmentation cases over a 3-year
      period from January of 1998 to January of 2001. Implant selection that did not
      comply with the parameters of the system was necessary in only eight cases. The
      TEPID system is a simple, efficient, and clinically practical method that allows
      surgeons to base implant selection on clinically quantifiable, individual patient
      tissue characteristics.

PMID- 11965001
TI  - A clinical definition of an ideal nasal radix.
AB  - The authors developed a system of simple soft-tissue measurements to define the
      ideal proportions of the nose. These measurements provide the surgeon the
      parameters to assess when a nose is "balanced" and to define when the radix
      should be raised or lowered. A ratio of 2:1:1:0.75 for length, projection,
      height, and radix, respectively, defines the ideally balanced Caucasian nose.

PMID- 11965003
TI  - Digital photography for rhinoplasty.
AB  - Standardized, high-quality, preoperative photographs of the nose are critical for
      preoperative rhinoplasty planning, comparative postoperative assessment, and
      demonstration of surgical results. To produce these high-quality, reproducible
      photographs, it is essential to standardize lighting, to properly position the
      patient in standard views, to avoid lens distortion, and to maintain consistent
      camera-to-subject distances. Traditional photographic standards have been well
      documented in the literature; however, most do not address digital photography,
      and none address digital photography for rhinoplasty. Certain variables in
      digital photography that are not present in 35-mm photography can be critical to
      the appearance of the final image. Variables such as image color and contrast
      (which usually vary between digital cameras), focal length differences between 35
      mm and most digital cameras, the effect of resolution and compression on image
      quality, and the effect of the printing method used can affect the appearance of
      the external anatomy of the nose in the final print or image. Lack of detail in
      the external nasal anatomy becomes an issue if the surgeon uses the photograph
      intraoperatively for reference, as the authors do. Initially, the authors
      experienced difficulties with observing subtleties in the tip-defining points and
      tip anatomy using digital photography when compared with our traditional methods
      of 35-mm photography. The lack of detail in the external anatomy was most
      prevalent in the frontal and basal views. Thus, the authors have since tailored
      their photographic methods to document the rhinoplasty patient to maximize the
      visual information of the external nasal anatomy in the photographic and the
      printed image. This article is intended to review the photographic principles for
      standardized rhinoplasty photography, address the additional considerations
      necessary when using digital photography, discuss the printing variables that can
      affect overall quality of the printed image, and discuss the authors' new method
      of photographing the rhinoplasty patient.

PMID- 11965004
TI  - Treatment of thermal injuries from CO2 laser resurfacing.

PMID- 11965006
TI  - American Society of Plastic Surgeons: the state of the organization.

PMID- 11965007
TI  - The evolution of a cosmetic practice.

PMID- 11965008
TI  - No chimpanzees please.

PMID- 11965010
TI  - Concentric mastoplexy revisited.

PMID- 11965011
TI  - Defining perforator flaps: what is really perforated?

PMID- 11965012
TI  - Management of hooding of vagina with adduction contracture of thighs in
      association with sacral agenesis.

PMID- 11965013
TI  - Modification of the running tie-over dressing.

PMID- 11965014
TI  - Fat purification: survival of the fittest.

PMID- 11965015
TI  - A rare case of median cleft of the upper lip associated with enlarged frenulum
      and palatal masses.

PMID- 11965016
TI  - Linear nevus sebaceus complicated with metatypical carcinoma.

PMID- 11965017
TI  - Giant lipoma of the thigh in a patient with morbid obesity.

PMID- 11965018
TI  - Inflatable catheters in plastic surgery: a new use for the placement of tissue
      expanders.

PMID- 11965020
TI  - A simple procedure for axillae involved with hidradenitis.

PMID- 11965021
TI  - Caution in using botox in patients with previous frontal surgery.

PMID- 11965019
TI  - Treatment of postoperative bruising and edema with external ultrasound and manual
      lymphatic drainage.

PMID- 11965023
TI  - Scalp necrosis: an unusual presentation of giant cell arteritis.

PMID- 11965022
TI  - Management of soft-tissue problems in leg trauma in conjunction with application
      of Ilizarov fixator assembly.

PMID- 11965025
TI  - Thoracoscopy and transplantation: a new attractive tool.
AB  - BACKGROUND: Transplanted patients on immunosuppressive treatment have an
      increased risk of infections or neoplasms. Transplantation candidates with
      infection or a suspected malignancy are excluded from transplantation. In
      patients already transplanted, thoracoscopy can resolve complications or treat
      the pulmonary pathology without compromising the precarious existing reactive
      equilibrium. These patients require an approach that is as least traumatic as
      possible. METHODS: From September 1991 to December 2000, of 2068
      videothoracoscopic procedures carried out at our hospital, 2 were in patients who
      had undergone transplantation and 3 in candidates for kidney, liver, and bone
      marrow transplantation. Starting from our personal experience in
      videothoracoscopy as a diagnostic and therapeutic approach, the possibilities of
      the method in the field of transplantation are reported by a review of the
      literature carried out by consulting the reference systems of the most important
      data banks. CONCLUSIONS: In our experience, videothoracoscopy had a major impact
      on the management of candidates for transplant, because it allowed us to rule out
      or treat conditions that would have determined exclusion from a transplant
      program. In transplanted patients, videothoracoscopy allows a correct diagnosis
      and treatment with minimal trauma.

PMID- 11965026
TI  - Localized interleukin-10 gene transfer induces apoptosis of alloreactive T cells
      via FAS/FASL pathway, improves function, and prolongs survival of cardiac
      allograft.
AB  - We hypothesized that localized IL-10 gene transfer can induce alloreactive T cell
      apoptosis and tested this hypothesis with liposome-mediated ex vivo intracoronary
      IL-10 gene transfer using a functional heterotopic allograft heart transplant
      model in rabbits. Localized IL-10 overexpression prolonged cardiac allograft
      survival over three folds. In parallel with the time-course of IL-10
      overexpression, the percentage of apoptotic CD3+ cells among total CD3+ cells was
      significantly increased in the gene therapy group (36.5+/-3.9%) compared with
      that in the control group (6.2+/-2.6%, P<0.01) on postoperative day (POD) 3-6,
      and it was further increased (45.8+/-5.7%) on POD7-10. Apoptotic CD4+ and CD8+
      cells were also significantly increased in the gene group (P<0.01). In contrast,
      the percentage of apoptotic myocytes significantly decreased from 10.1+/-0.8% in
      the control group to 3.5+/-0.4% in the gene group on POD7-10 (P<0.01). This
      reduction was inversely correlated with the increase in the percentages of
      apoptotic CD4+ and CD8+ cells (P<0.01). The percentage of caspase-3 positive
      myocytes was significantly reduced, although percentages of caspase-3 positive
      CD4+ and CD8+ cells were markedly increased in the gene group (P<0.01). Moreover,
      about 60-80% of apoptotic T lymphocytes expressed Fas in the gene group compared
      with less than 10% in the control group (P<0.01). These results suggest that
      localized IL-10 gene transfer induces alloreactive T cell apoptosis via the
      Fas/FasL pathway that may contribute to the alleviated acute rejection, improved
      cardiac function, and prolonged survival in the IL-10 gene-treated cardiac
      allografts.

PMID- 11965027
TI  - Prolonged survival in rat liver transplantation with mouse monoclonal antibody
      against an inducible costimulator (ICOS).
AB  - BACKGROUND: An inducible costimulator (ICOS), a recently identified costimulatory
      receptor with a close structural homology to CD28 and CTLA4, is expressed on
      activated T cells. Interaction with its ligand on antigen-presenting cells
      stimulates T-cell proliferation to produce a different spectrum of cytokine. The
      inhibition of ICOS-mediated signal transduction by an anti-ICOS antibody is
      considered to be capable of protecting against graft rejection in organ
      transplantation. METHODS: An anti-rat ICOS antibody was intravenously
      administered into recipients of dark Agouti-to-Lewis liver transplantations. The
      recipient lymphocytes from mesenteric lymph nodes were harvested on day 7 after
      transplantation for fluorescence-activated cell sorting analysis, and tissue
      specimens from the grafts were removed for histologic evaluation. Antigen
      specific T-cell proliferation responses were assessed in vitro with anti-ICOS
      antibody. RESULTS: Monotherapy with the antibody significantly prolonged the
      graft survival time by inhibiting T-cell activation and its proliferation
      response. The graft-infiltrating cells, both CD4 and CD8 T cells, were not
      completely reduced even when rats were administered the antibody, whereas the
      expression of ICOS almost completely disappeared in these cells. CONCLUSIONS: T
      cell activation through the ICOS costimulatory pathway plays an important role in
      graft rejection, and manipulating its pathway is an effective method for
      modulating transplantation immunity.

PMID- 11965028
TI  - Cultured autologous fibroblasts augment epidermal repair.
AB  - BACKGROUND: Autologous dermal fibroblasts may be useful in the treatment of skin
      wounds and for the enhancement of keratinocyte proliferation. This paper
      addressed the following questions: (1) can cultured fibroblasts (CF) be
      transplanted as suspensions to full-thickness skin wounds and do they influence
      wound healing; (2) will the transplanted CF be integrated into the new dermis;
      (3) can a transgene that encodes a secretable marker, human epidermal growth
      factor (hEGF), be expressed in the wound fluid by the transplanted CF; and (4) do
      CF cotransplanted with cultured keratinocytes (CK) influence the rate of wound
      healing? METHODS: Suspensions of CF were transplanted alone or together with CK
      to full-thickness wounds covered with liquid-containing chambers in an
      established porcine model. RESULTS: Transplantation of CF accelerated
      reepithelialization as determined from wound histologies and sequential
      measurements of protein efflux over the wound surface. CF transfected with a
      marker gene, beta-galactosidase, resulted in in vivo gene expression and
      demonstrated that transplanted CF integrated into the developing dermis.
      Transplantation of hEGF gene-transfected CF resulted in significant hEGF
      expression in wound fluid. The hEGF levels peaked at day 1 (2450 pg/ml) and then
      sharply decreased to low levels on day 6. CF cotransplanted with CK led to
      greater number of keratinocyte colonies in the wound and accelerated
      reepithelialization as compared with CK alone. CONCLUSIONS: Transplanted CF
      integrated into the dermis, accelerated reepithelialization, and improved the
      outcome of CK transplantation. CF may also be used for the expression of
      transgenes in wound and wound fluid.

PMID- 11965030
TI  - Tacrolimus (FK506) and cyclosporine reduce the uptake and transport of particles
      into rabbit Peyer's patches.
AB  - Tacrolimus (FK) and cyclosporine (Cs) are potent immunosuppressants that
      effectively prevent the rejection of transplanted organs including liver and
      small intestine. Our study examined the effects of these immunosuppressants on
      Peyer's patches, which play an important role in mucosal immune response through
      uptake and transport of enteric microorganisms and macromolecules in the gut
      associated lymphoid tissues. After administration of FK and Cs, we assessed
      changes in lymphoid follicle structure and quantified the uptake and transport of
      particles in the follicle associated epithelium (FAE) including M cells, using
      fluorescent latex microspheres in rabbit Peyer's patches. Rabbits, five in each
      group, received oral administration of FK (3.2 mg/kg), Cs (10 mg/kg), or
      phosphate-buffered saline daily for 7 days. After 2 days of withdrawal, rabbits
      were anesthetized, and received injections with 2 ml of the suspension of 0.5
      microm fluorescent microspheres (1010/ml) into ligated intestinal segments
      containing Peyer's patches. After 2 hr of gentle agitation, segments were
      removed, rinsed, fixed with periodate-lysine-2% paraformaldehyde, frozen, and
      sections were stained with fluorescent phalloidin to label brush border actin
      filaments. The size of the lymphoid follicles in each group was measured under a
      light microscope. The number of microspheres in follicles was assessed in
      graphically defined areas of follicles from each group. In addition,
      immunohistochemical analysis of CD43 and MHC-II positive cells in FAE of lymphoid
      follicles of each group was performed. FK and Cs significantly reduced the height
      of lymphoid domes and the height and width of follicles, as compared to those of
      controls. In both FK and Cs groups, the numbers of microspheres that adhered,
      were taken up and were transported into lymphoid follicles were smaller than in
      controls, indicating that their movement rates into deep layers were markedly
      reduced. Furthermore, FK and Cs reduced the mean numbers of CD43 and MHC-II
      positive cells in FAE per unit area (mm2) as compared with controls. These
      findings suggest that FK and Cs may produce immunosuppressive effects, at least
      in part, through reduction of the uptake and transport of particles into Peyer's
      patches, and by reduction of the number of immunoreactive cells in FAE of Peyer's
      patches.

PMID- 11965029
TI  - Role of cyclic nucleotides in ischemia and reperfusion injury of canine livers.
AB  - BACKGROUND: In a series of canine liver ischemia experiments, we have shown that
      amelioration of hepatic injury is achievable by the inhibition of
      vasoconstriction, cytokine production, platelet aggregation, and neutrophil
      infiltration. Cyclic adenosine diphosphate (cAMP) was considered to be involved
      in most of these events. In our study, we tested our hypothesis that augmentation
      of endogenous cAMP by phosphodiesterase (PDE) 3 inhibitor, amrinone (AM), or
      adenylate cyclase stimulator, NKH477 (NKH), could attenuate ischemia and
      reperfusion injury of the liver. METHODS: Thirty-six beagle dogs were used. They
      were divided into group CT (untreated control), group AM, group NKH, and group CB
      (treated by both agents). AM or NKH were administered i.v. 1 hr before ischemia
      (group preAM and group preNKH) or 15 min before reperfusion (pos-AM and postNKH).
      Combination group animals were treated only before ischemia. Animal survival,
      hepatic tissue blood flow, liver enzymes, platelet counts, energy metabolism,
      hepatic cAMP and cyclic guanosine 3',5'-cyclic monophosphate levels, and
      histopathology were analyzed. RESULTS: Two-week animal survival was significantly
      improved by pre- or posttreatment with either agent. After reperfusion, hepatic
      tissue blood flow, liver enzyme release, platelet counts, energy metabolism,
      tissue cAMP levels, and histological architecture were also ameliorated markedly.
      Combination of both agents induced severe liver damage and lethal hypotension. AM
      treatment exhibited more protective effects than NKH, particularly when it was
      given before ischemia. Interestingly, not only cyclic guanosine 3',5'-cyclic
      monophosphate, were also restored at higher levels after reperfusion by
      preischemia treatment. CONCLUSIONS: Administration of amrinone or NKH477
      maintained hepatic tissue concentrations of cyclic nucleotides, and attenuated
      ischemia and reperfusion injury of the liver. Thus, regulation of hepatic tissue
      cyclic nucleotides is an important alternative for prevention of hepatic damage
      in liver preservation and surgery.

PMID- 11965032
TI  - Endothelial function in pigs transgenic for human complement regulating factor.
AB  - BACKGROUND: Expression of human complement regulating factor (hCRF) in porcine
      organs prevents hyperacute rejection of these organs after xenotransplantation to
      nonhuman primates. Experiments were designed to characterize endothelial and
      smooth muscle function of arteries from pigs transgenic for hCD46. METHODS:
      Arterial blood from outbred pigs transgenic for hCD46 expression and
      nontransgenic animals of the same lineage was analyzed for angiotensin-converting
      enzyme (ACE), C-type natriuretic peptide (CNP), and nitric oxide. Aortic
      endothelial cells were prepared for measurement of mRNA or activity for nitric
      oxide synthase (NOS). Rings cut from femoral and pulmonary arteries were
      suspended in organ chambers for measurement of isometric tension. RESULTS: CNP
      was significantly greater, ACE was similar, and nitric oxide was significantly
      less in plasma from transgenic compared with nontransgenic pigs. Neither mRNA nor
      activity of NOS differed between the groups. Endothelium-dependent relaxations to
      bradykinin and acetylcholine but not the calcium ionophore were shifted
      significantly to the left in femoral and pulmonary arteries from hCD46 transgenic
      pigs compared with nontransgenic pigs. The ACE-inhibitor captopril augmented
      relaxations similarly in both groups, but NG-monomethyl-L-arginine (L-NMMA) did
      not inhibit relaxations in rings from transgenic pigs. CONCLUSIONS: Data suggest
      that expression of hCD46 on endothelium of pigs selectively augments endothelium
      dependent relaxations to bradykinin by increased release of endothelium-derived
      factors other than nitric oxide. There does not seem to be any change in activity
      of ACE or NOS with expression of the human protein. Increased relaxations to
      bradykinin may be beneficial in lowering vascular resistance when transgenic
      organs are used for xenotransplantation.

PMID- 11965031
TI  - Inhibition of endothelin-1 improves survival and vasculopathy in rat cardiac
      transplants treated with cyclosporine.
AB  - BACKGROUND: In animal models, endothelin-1 (ET-1) blockade attenuates transplant
      vasculopathy and chronic allograft dysfunction even in the absence of
      cyclosporine (CsA). As CsA has side effects and ET-1 antagonism alone has
      significant benefits, we postulated that allograft survival could be
      significantly improved by combining an endothelin-converting enzyme inhibitor
      with low-dose CsA. METHODS: Survival of Lewis to Fisher 344 rat heterotopic
      cardiac allografts was determined in untreated animals and compared with those
      treated with high-dose CsA (62 mg/kg i.m. on day 2), low-dose CsA (25 mg/kg), an
      endothelin-converting enzyme inhibitor, phosphoramidon (PA, 10 mg/kg/day), or low
      dose CsA + PA. RESULTS: Untreated allografts had a median survival of 16 days
      compared with 20 days for low-dose CsA. Grafts treated with PA survived for 28
      days, and combination of PA and low-dose CsA improved median survival to 47 days
      (P<0.01). Median survival with combination therapy was similar to that for high
      dose CsA (42 days). To explore mechanisms underlying the benefits of combination
      therapy, cardiac allografts treated as above (n=4 each group) were explanted at
      20 d and analyzed for parenchymal rejection, neointimal vasculopathy, myocardial
      fibrosis, and macrophage infiltration. Low-dose CsA alone but not PA improved
      parenchymal rejection; in contrast, PA alone but not low-dose CsA improved
      vasculopathy. Both parenchymal rejection and vasculopathy were improved by
      combination therapy with low-dose CsA and PA. Unlike CsA, inhibition of ET-1
      biosynthesis significantly reduced myocardial fibrosis in allografts.
      CONCLUSIONS: These results suggest that the combination of low-dose CsA and
      endothelin-converting enzyme inhibition may prove useful to improve long-term
      graft survival while minimizing potential side effects of CsA.

PMID- 11965033
TI  - Kinetics of transplant arteriosclerosis in MHC-Class I mismatched and fully
      allogeneic mouse aortic allografts.
AB  - INTRODUCTION: Transplant arteriosclerosis is still the major complication for
      long-term allograft survival in clinical transplantation. The aim of our study
      was to investigate the impact of MHC disparity on the kinetics of the development
      of transplant arteriosclerosis. METHODS: MHC-class I mismatched CBK (H2k+Kb) or
      fully allogeneic C57BL/10 (H2b) aortic allografts were transplanted into CBA.CA
      (H2k) recipients; syngeneic grafts were used as controls. Aortic grafts were
      analyzed on days 7, 14, and 30 after transplantation by performing morphometry,
      immunohistochemistry and quantitative reverse-transcriptase polymerase chain
      reaction (RT-PCR) for the detection of intragraft cytokine mRNA production. Donor
      specific alloantibody production was measured by FACS analysis. RESULTS: Intimal
      proliferation developed more rapidly in fully allogeneic grafts (direct and
      indirect allorecognition by CD4+ T cells) compared to MHC-class I mismatched
      grafts (indirect allorecognition only by CD4+ T cells) (day 7: 6+/-7 vs. 2+/-3%;
      day 14: 17+/-8 vs. 5+/-1%; day 30: 65+/-5 vs. 38+/-7% (C57BL/10 vs. CBK).
      However, by day 60, the level of intimal proliferation in the MHC-class I
      mismatched grafts was equivalent to that observed with fully allogeneic grafts on
      day 30. There was also a marked delay in the kinetics of graft infiltration by
      CD4+, CD8+, CD11b+, and CD40+ leukocytes and alloantibody production when CD4+ T
      cells were only activated via indirect presentation (MHC-class I mismatched
      grafts). Expression of interferon-gamma, interleukin-2, and interleukin-4
      correlated with the kinetics of leukocyte infiltration, whereas interleukin-10,
      interleukin-12p40, iNOS, and TGF-beta1 showed a distinct pattern of expression.
      CONCLUSIONS: These data demonstrate that the degree of MHC incompatibility
      between donor and recipient markedly influences the kinetics of the development
      of transplant arteriosclerosis. The onset of disease was delayed when grafts were
      mismatched for only MHC-class I antigens, but ultimately reached the same levels
      as seen in fully allogeneic grafts. The pattern of leukocyte infiltration and the
      kinetics of cytokine production suggest that in the MHC-class I mismatched grafts
      CD4+ T cells responding via the indirect pathway might play an important role in
      the development of transplant arteriosclerosis.

PMID- 11965034
TI  - Influenza and parainfluenza respiratory viral infection requiring admission in
      adult lung transplant recipients.
AB  - BACKGROUND: Although influenza and parainfluenza viruses commonly cause
      respiratory tract infections in the community, their incidence and clinical
      implications in adult lung transplant recipients have received little attention.
      METHODS: We performed a retrospective cohort study of influenza and parainfluenza
      viral infections in adult lung transplant recipients at the University of
      Pittsburgh Medical Center. RESULTS: Between January 1989 and March 1999, 39 cases
      (single-lung 25, double-lung 14) of influenza or parainfluenza respiratory viral
      infection were identified at a mean of 1.7 years (SD+/-1.4) after
      transplantation. The mean length of admission was 7 days. The cases included 15
      patients with influenza (A, 11; B, 4) and 24 with parainfluenza (para1, 7; para2,
      2; para3, 15). The median age at diagnosis was 48 years; there were 19 females
      and 20 males. Symptoms were reported in 30 patients and lasted for a median of 7
      days before admission. These included cough (64%), shortness of breath (56%), and
      temperature elevation (33%). Chest infiltrates were seen in 14 (36%) patients,
      and 5 (13%) of them required intubation and mechanical ventilation. Viral
      pneumonia was diagnosed in 10 (5 influenza and 5 parainfluenza) patients, and
      concurrent bacterial pneumonia occurred in 4 patients. Transbronchial biopsy was
      performed in 36 patients, of whom 23 (64%) showed some degree of acute allograft
      rejection. CONCLUSION: Influenza and parainfluenza respiratory viral infections
      are associated with significant morbidity in adult lung transplant recipients.
      Active vaccination programs and the development of new antiviral agents active
      against these viruses are important for prevention.

PMID- 11965036
TI  - Severe amnesia associated with human herpesvirus 6 encephalitis after bone marrow
      transplantation.
AB  - BACKGROUND: Human herpesvirus 6 (HHV-6) appears to have a predilection for
      immunocompromised patients and has been implicated as a cause of posttransplant
      encephalitis. However, the pathogenesis, as well as the appropriate means of
      diagnosis and treatment of HHV-6 encephalitis is unclear. METHOD: We describe a
      case of a 20-year-old male university student with anemia who presented with an
      acute, severe amnesia 1 month after bone marrow transplantation. His illness was
      subsequently attributed to HHV-6 encephalitis. RESULTS: Cerebrospinal fluid
      analysis was consistent with encephalitis and polymerase chain reaction confirmed
      the presence of HHV-6 DNA in both cerebrospinal fluid and serum. No other herpes
      virus particles were detected. MRI showed bilateral hippocampal involvement.
      Treatment with acyclovir resulted in a decrease in serum HHV-6 DNA to
      undetectable levels, coincident with improvement of both memory and lesions on
      MRI. CONCLUSIONS: This case provides strong clinical and radiological evidence of
      the reversibility of this disease process and supports the recommendations for
      empiric treatment of post transplant patients with laboratory evidence of HHV-6
      infection, culture or polymerase chain reaction, plus clinical symptoms
      compatible with HHV-6 infection.

PMID- 11965035
TI  - Expression of protective genes in human renal allografts: a regulatory response
      to injury associated with graft rejection.
AB  - BACKGROUND: Long-term survival of a graft requires inhibition of host immune
      effectors, but protective responses emanating from the graft might be equally
      important. Expression of the "protective" genes A20, heme-oxygenase-1 (HO-1), and
      Bcl-xL in rodent allo and xenografts correlates with long-term survival. Little
      is known of the pattern of expression of such protective genes and the
      implication thereof in clinical transplantation. METHODS: We analyzed, by
      quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and
      immunohistochemistry, expression of A20, HO-1, and Bcl-xL in 31 renal allograft
      biopsies from patients with suspected rejection. RESULTS: A20 is not expressed in
      nonrejecting (NR) grafts. Its expression is increased in grafts undergoing acute
      and chronic rejection (AR and CR) but is weaker in CR. HO-1 is not expressed in
      NR grafts; it is up-regulated in AR but not CR. Bcl-xL is detected in all
      biopsies with decreased levels in CR. Expression of A20, HO-1, and Bcl-xL
      localizes mainly to endothelial, smooth muscle, and infiltrating mononuclear
      cells. CONCLUSIONS: This data demonstrate that A20 and HO-1 are up-regulated in
      response to immune injury inferred by AR. Given the antiapoptotic and
      antiinflammatory functions of these genes, we hypothesize that their expression
      survives to limit graft injury by maintaining cell viability and controlling
      inflammation. Their reduced expression in CR as compared with AR represents
      either inadequate response to injury or a sequelae of prior injury that
      jeopardizes further tissue response to immune attack.

PMID- 11965037
TI  - DNA sequencing of viral capsid protein VP-1 region in patients with BK virus
      interstitial nephritis.
AB  - BACKGROUND: Mutations in the viral capsid protein VP-1 region are associated with
      increased pathogenicity of polyomavirus in experimental systems. This study
      sought to determine whether analogous viral genetic changes occur in human BK
      virus (BKV) interstitial nephritis (ISN). METHODS: PCR was used to amplify a 94
      bp nucleotide sequence of the viral capsid protein VP-1 region (positions 1740
      1833, Dun numbering) in 49 biopsies obtained from 24 patients with BKV-ISN. DNA
      sequencing was performed by the dideoxy method. RESULT: The VP-1 region was
      highly polymorphic and 22 "hot spots" of sequence variability were noted.
      Genotypes I, II, and IV were assigned to 13, 1, and 5 cases, respectively, but 5
      cases could not be unambiguously classified due to sequence heterogeneity at
      sites used to discriminate between genotypes. Even in cases where genotypes could
      be assigned, only 5 biopsies showed complete sequence identity with published
      genotype sequences. Sequential biopsies showed temporal changes in one or more
      nucleotides in all patients with multiple samples. In one patient, the initial
      biopsy showed viral genotype 1, although subsequent biopsies showed complex
      genetic patterns, including a biopsy consistent with viral genotype IV.
      CONCLUSIONS: Many viral strains associated with BKV-ISN are difficult to classify
      and possibly distinct from those described in kidney transplant recipients
      without BKV-ISN. VP-1 sequences undergo continual modification as patients are
      followed in time. This genetic instability could conceivably have implications
      for evasion of host immunity and development of resistance to antiviral drugs.

PMID- 11965038
TI  - Graft survival and graft function of pediatric en bloc kidneys in paraaortal
      position.
AB  - BACKGROUND: En bloc kidneys from pediatric donors are regarded as questionable
      with respect to the safety and quality of the transplant outcome. Therefore, we
      retrospectively studied graft outcome and graft function of our 56 en bloc
      kidneys transplanted in paraaortal position between 1992 and 1999. METHODS: Graft
      outcome of en bloc kidneys (group A) was compared with graft outcome of single
      cadaveric adult donor kidneys (group B). Matched pairs were generated regarding
      HLA-missmatch, cold ischemic time, recipient age, body mass index, and systolic
      arterial blood pressure. RESULTS: Allograft survival rates of pediatric en bloc
      kidneys at 1, 3, and 5 years were significantly lower (group A: 78, 70, 70% vs.
      group B: 92, 92, 81%, P<0.05). Lower survival rate was caused by a higher number
      of graft losses in the early postoperative period (group A: 21% vs. group B: 4%,
      P<0.01) due to vascular complications. Main risk factor for graft loss was donor
      age of less than 12 months. Five years after transplantation serum creatinine of
      pediatric en bloc kidneys was significantly better than of adult kidneys (0.9+/
      0.06 vs. 1.8+/-0.2 mg/dl, P<0.001). CONCLUSION: En bloc kidneys show a high
      percentage of graft survival with excellent long-term graft function. However,
      the early postoperative period carries a higher risk of graft loss in very young
      donors due to vascular complications. In the face of donor shortage en bloc
      kidneys from pediatric donors can successfully be transplanted in a paraaortal
      position.

PMID- 11965040
TI  - Effect of core pancreas temperature during cadaveric procurement on human islet
      isolation and functional viability.
AB  - BACKGROUND: Success of human pancreatic islet isolation depends largely on the
      techniques used during pancreas procurement and the quality of the gland. Warm
      ischemia of the pancreas of any duration during organ procurement may be
      detrimental to subsequent islet yield and functional viability of the islets. The
      aim of this study was to correlate pancreas procurement technique with the core
      temperature within the pancreas during in situ procurement to the recovery and in
      vitro function of isolated human islets. METHODS: Alternative pancreata were
      recovered from human cadaveric organ donors with needle-point myocardial
      temperature probes placed within the body of the pancreas. After vascular
      flushing with University of Wisconsin organ preservation solution, the first
      group of human pancreata were removed after standard liver and kidney procurement
      followed by in situ dissection of the pancreas. The second group of pancreata
      were removed using a similar protocol, except that the lesser sac was opened (and
      the spleen was mobilized to the midline) rapidly at the time of aortic cross
      clamp. An additional 3-4 L of ice slush solution was placed behind and in front
      of the pancreas and replenished throughout the procurement process for the liver
      and kidneys. Immediately after recovery, in both groups, the pancreas was placed
      in cold University of Wisconsin solution and transported to the islet isolation
      laboratory for processing. Islets were isolated using a standard protocol of
      Liberase perfusion via the duct, gentle mechanical dissociation, and Ficoll
      purification. RESULTS: The absence of in situ ice-chilling of the entire pancreas
      during liver and kidney procurement caused the core pancreas temperature to rise
      to a peak of 18.2 degrees C; but when the pancreas was surrounded and replenished
      with iced saline slush, the core pancreas temperature was maintained at
      approximately 4 degrees C. The lower pancreas temperature correlated with a
      significantly higher recovery of islets in the group of pancreata surrounded with
      iced saline (223+/-35x10(3) IE vs. 103+/-26x10(3) IE; mean +/- SEM). Functional
      ability of the islets was also significantly improved in glucose static
      incubation, with a stimulation index of 4.4+/-0.3 in the iced-saline pancreas
      group versus 3.0+/-0.4 in the standard procurement group (P<0.05, paired t test).
      CONCLUSIONS: Procurement technique and the maintenance of a low temperature of
      the pancreas are critical to subsequent islet recovery and function. Maintaining
      a low pancreas temperature during procurement through the addition and
      replenishment of iced saline slush surrounding the anterior and posterior aspects
      of the pancreas greatly improves islet yield and functional viability of the
      isolated islets and is essential for success in clinical islet transplantation.

PMID- 11965039
TI  - Daclizumab induction, tacrolimus, mycophenolate mofetil and steroids as an
      immunosuppression regimen for primary kidney transplant recipients.
AB  - BACKGROUND: Recent reports have demonstrated the efficacy of interleukin-2
      receptor blockers in lowering the incidence of early acute rejection in
      cyclosporine-treated kidney recipients when compared to patients not induced with
      an antibody product. The addition of daclizumab to a tacrolimus-mycophenolate
      mofetil-based immunosuppressive protocol was tested to evaluate whether there
      might be an additional reduction of the risk of rejection after renal
      transplantation. METHODS: Since March 1998, we studied the effect of daclizumab
      in a nonrandomized, prospective study of 233 sequential recipients of first renal
      transplant. They were retrospective compared with a control group of 225 renal
      transplant recipients receiving a 10-day course of OKT3 induction, and
      tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. The study
      group received the same immunosuppressive regimen with the addition of daclizumab
      at 1 mg/kg for five doses over 10 weeks in the place of OKT3 therapy. There was
      at least 1HLA DR antigen compatibility match present between all donors and
      recipients. Patients were followed for 1 year after renal transplantation for the
      incidence of biopsy-proven acute rejection, patient and graft survival, and
      adverse events. RESULTS: At 12 months, patient and graft survival for the
      daclizumab was 98 and 96 vs. 96 and 94% for the OKT3 group, respectively, and
      were not statistically different. Acute rejection rates (<6 months) were lower in
      the daclizumab group as compared with the OKT3 group, i.e., 5 (2.1%) vs. 16
      (7.1%) (P=0.011) respectively. The incidence of infection requiring
      hospitalization appeared to be lower with daclizumab (7.3 vs. 16%, P<0.0036) with
      a similar trend with cyclomegalovirus infection, i.e., 1.6 vs. 4%, respectively
      (P=0.14). CONCLUSIONS: The combination of daclizumab, tacrolimus, mycophenolate
      mofetil, and steroids is safe and effective for kidney transplant recipients in
      lowering the incidence of early acute rejection and without any increase in
      morbidity when compared to our previous protocol, which may have an eventual
      impact in long-term graft survival.

PMID- 11965041
TI  - Tumor necrosis factor beta gene polymorphisms associated with urinary tract
      infections after renal transplantation.
AB  - INTRODUCTION: We investigated whether tumor necrosis factor (TNF) beta(low) or
      TNFbeta(high) alleles predicted susceptibility to infection or rejection after
      renal transplantation. METHODS: TNFbeta alleles were determined in 137 (ESRD)
      patients and correlated with urinary tract infections and rejection within 60
      days among 75 consecutive renal transplant recipients. RESULTS: TNFbeta low was
      more prevalent among African-Americans than caucasians (83 vs. 63%, P=0.02).
      After renal transplantation, patients with TNFbeta low experienced more urinary
      tract infections (50 vs. 10%, P=0.002). The incidence of TNFbeta low and urinary
      tract infections were equivalent in patients treated with mycophenolate
      mofetil/cyclosporine (CsAA) (n=37) versus mycophenolate mofetil/tacrolimus
      (n=38). TNFbeta low was not associated with the incidence of delayed graft
      function (5 vs. 2, P=NS), early rejection (21 vs. 18%, P=NS) or actuarial 1-year
      graft survival (96 vs. 90%, P=NS). CONCLUSIONS: TNFbeta low was associated with
      urinary tract infections and TNFbeta high was associated with freedom from
      urinary tract infections. Neither gene correlated with rejection or l-year graft
      survival.

PMID- 11965042
TI  - Incidence of donor renal fibromuscular dysplasia: does it justify routine
      angiography?
AB  - BACKGROUND: The use of digital subtraction angiography (DSA) versus helical CT
      angiography (CTA) or MR angiography (MRA) for live renal donor evaluation is
      still controversial. Although CTA and MRA can detect some proximal moderate to
      severe arterial changes caused by fibromuscular dysplasia (FMD), mild and distal
      moderate FMD are not detected well without angiography. METHODS: This is a
      retrospective chart review of all potential, normotensive live renal donors at
      our center from July 1995 to June 2001. One hundred fifty-nine patients completed
      the donor evaluation process and underwent DSA. RESULTS: Seven cases of FMD, an
      incidence of 4.4%, were discovered. These patients were eliminated from donation.
      The distribution of renal vessels for our 159 patients was single arteries
      bilaterally, 64.8%; single left with multiple right, 16.4%; double left with
      single right, 9.4%; and multiple bilateral arteries, 9.4%. Three of the seven FMD
      patients had bilateral disease. Two of the seven (28.6%) FMD patients have
      subsequently required antihypertensive medications, with one requiring
      angioplasty of a progressive FMD stenotic lesion. CONCLUSIONS: We are concerned
      that CTA or MRA may overlook mild cases of DSA-detectable FMD. All seven FMD
      patients had single left renal arteries and would have undergone left donor
      nephrectomy. This would have resulted in their remaining right native kidneys
      having mild to moderate FMD in six of seven patients and in four donor kidneys
      having mild to moderate FMD. The need for antihypertensive medications in two of
      these seven potential donors within 4 years of their evaluation supports previous
      literature reports.

PMID- 11965043
TI  - Depletion of recipient CD4+ but not CD8+ T lymphocytes prevents the development
      of cardiac allograft vasculopathy.
AB  - BACKGROUND: We have described that chimeric rat hearts bearing recipient-type
      antigen-presenting cells (APCs) do not reject acutely, but develop cardiac
      allograft vasculopathy (CAV) in untreated recipients. This suggests that CAV is
      triggered either by CD8+ direct allorecognition or by CD4+ indirect
      allorecognition. To determine the allorecognition pathway responsible for CAV in
      this model, recipients of chimeric hearts underwent either CD8+ or CD4+ T cell
      depletion. METHODS: Chimeric hearts were created via bone marrow transplantation
      in two fully major histocompatibility-mismatched rat strain combinations. DA
      recipients were thymectomized and treated with Ox8 and Ox38 murine monoclonal
      antibodies, which deplete CD8+ and CD4+ T cells, respectively. Chimeric PVG
      hearts bearing DA APCs, abbreviated PVG(DA), were heterotopically transplanted
      into recipients undergoing thymectomy alone or recipients undergoing thymectomy
      plus either CD4+ or CD8+ T cell depletion. RESULTS: PVG(DA) allografts survived
      100 days, but developed CAV in thymectomized recipients and in those permanently
      depleted of CD8+ T cells. In contrast, chimeric hearts transplanted into
      permanently CD4+ T cell-depleted recipients survived 100 days and demonstrated no
      evidence of CAV. CONCLUSIONS: In this specific strain combination, recipient CD8+
      T cells are neither necessary nor sufficient for the development of CAV, whereas
      recipient CD4+ T cells are required for the development of CAV. These findings
      suggest that CAV is dependent on CD4+ indirect allorecognition and that CD8+
      direct allorecognition stimulated by nonprofessional APCs plays a minor role.

PMID- 11965044
TI  - Postoperative administration of donor B cells induces rat kidney allograft
      acceptance: lack of association with Th2 cytokine expression in long-term
      accepted grafts.
AB  - BACKGROUND: Although donor leukocytes are only thought to prolong survival when
      administered before transplantation, recent evidence shows that they are
      effective at transplantation. This study aims to identify the leukocyte subset
      that is most active in prolonging kidney allograft survival and examine the
      cytokine expression in long-term acceptance. METHODS: PVG rat kidneys were
      transplanted to completely MHC class I and class II-mismatched DA recipients.
      Donor B cells or T cells, purified by negative selection, were injected i.v. at
      the time of transplantation. Expression of interleukin (IL)-2, IL-4, IL-10,
      interferon (IFN)-gamma, and transforming growth factor-beta mRNA was measured by
      quantitative real-time polymerase chain reaction (PCR). Immunohistochemical
      analysis and terminal deoxynucleotide transferase-mediated dUTP nick-end
      labelling (TUNEL) staining was used to identify infiltrating cells and apoptotic
      cells, respectively, in sections of kidney allografts. RESULTS: Median kidney
      graft survival time (MST) of B cell-treated animals (n=5) was >300 days, compared
      with 7 days in untreated animals (n=7) (P=0.003), whereas animals treated with
      the same number of T cells (n=6) had a MST of 17 days (P=0.1 vs. untreated,
      P=0.03 vs. B cell-treated). Examination of the long-term (>300 days) accepted
      grafts from B cell-treated recipients showed little evidence of kidney damage but
      a moderate perivascular infiltrate consisting of T and B cells. This infiltrate
      seemed to be quiescent because there was no detectable expression of IL-2
      receptors or of apoptotic cells. It produced little or no cytokine mRNA, because
      expression in the long-term accepted grafts was similar to levels in normal
      kidneys or syngeneic transplants. There was a marked increase of cytokine mRNA
      early after transplantation in both leukocyte-treated and untreated grafts, with
      more rapid appearance of IFN-gamma and IL-10 in leukocyte-treated grafts.
      CONCLUSIONS: Donor B cells efficiently induce long-term acceptance of
      transplanted kidneys in a fully MHC-mismatched rat model when administered at
      transplantation, by a mechanism that seems to be independent of Th2 cytokine
      expression within the long-term accepted graft.

PMID- 11965045
TI  - Development of autoimmunity after skin graft rejection via an indirect
      alloresponse.
AB  - BACKGROUND: T cell allorecognition occurs through direct contact with donor
      peptide: MHC complexes on graft cells and through indirect recognition of donor
      derived determinants expressed by recipient MHC molecules. As both indirect
      allorecognition and autoantigen recognition are self-restricted, we hypothesized
      that chronic activation of indirectly primed T cells might result in determinant
      spreading to involve autoantigens, analogous to that which occurs during chronic
      autoimmune diseases. METHODS: We placed C57BL/6 MHC II knockout (B6 II-/-) skin
      grafts onto BALB/c SCID mice reconstituted with wild-type (WT) CD4+ T cells.
      Under these conditions the CD4+ cells could not recognize any antigen on the
      graft, but could respond through the indirect pathway. CD4+ cell-mediated
      rejection of WT B6 skin was studied to determine if autoreactivity was induced
      after direct allorecognition. Recall immune responses against donor- and self
      stimulator cells were determined by ELISPOT and animals were tested for their
      ability to reject second isografts. RESULTS: WT allografts were rejected by day
      14 although B6 II-/- grafts underwent delayed rejection over 4-5 weeks. CD4+
      cells reisolated from the recipients of the MHC II-/- grafts, but not from the
      recipients of WT grafts, vigorously produced interferon-gamma and interleukin-2
      in response to self, BALB/c stimulators. These autoreactive CD4+ T cells mediated
      rejection of a second isogenic BALB/c skin graft, demonstrating that the
      autoimmune response was pathogenic. CONCLUSION: Autoreactivity can develop after
      transplant rejection via the indirect pathway. Although the direct alloresponse
      is likely to be the driving force in acute graft rejection, posttransplantation
      induced autoimmune responses may be important elements of delayed or chronic
      rejection.

PMID- 11965046
TI  - Expression of minor histocompatibility antigen, HA-1, in solid tumor cells.
AB  - BACKGROUND: Minor histocompatibility antigen (mHag) induces and mounts graft
      versus-host disease after allogeneic hematopoietic stem cell transplantation.
      Among several mHags, HA-1 is one that acts alone and is the most studied. It is
      suggested that HA-1 may be one of the immunodominant antigens inducing not only
      graft-versus-host disease but also graft-versus-malignancy effects. There are
      some reports that mHag HA-1-specific cytotoxic T lymphocytes generated from an HA
      1-negative donor can lyse HA-1-positive leukemic cells. However, the tissue
      distribution of HA-1 has been described as restricted to the cells of the
      hematopoietic lineage. METHODS: We examined the HA-1 expression in peripheral
      blood mononuclear cells (PBMNC), leukemia/lymphoma cell lines, solid tumor cell
      lines, and paired samples of tumor and normal tissues from individual cancer
      patients by quantitative reverse-transcription polymerase chain reaction.
      RESULTS: We found that mRNA of HA-1 is expressed in all leukemia/lymphoma cell
      lines and PBMNC. Most of the leukemia/lymphoma cell lines have the same levels of
      HA-1 expression as a leukemia/lymphoma cell line, Raji. The expression levels of
      human PBMNC were 14- to 19-fold higher than those of Raji. Among 32 solid tumor
      cell lines, 7 showed >50% expression levels compared with Raji. CONCLUSIONS: HA-1
      expression in the mRNA level is higher in cells of hematopoietic origin, but this
      tissue distribution is not strictly restricted. Some solid tumor cells and
      tissues express HA-1 gene equal to hematopoietic cells.

PMID- 11965047
TI  - Promotion of hepatic ischemia/reperfusion injury by IL-12 is independent of
      STAT4.
AB  - BACKGROUND: We have recently demonstrated a role for interleukin-12 (IL-12) in
      the induction and development of hepatic ischemia/reperfusion injury. IL-12
      mediates its effects through the transcription factor, signal transducer and
      activator of transcription-4 (STAT4). Therefore, we investigated the response to
      hepatic ischemia/reperfusion in STAT4-deficient mice. METHODS: Wild-type and
      STAT4-deficient mice were subjected to 90 min of partial hepatic ischemia
      followed by reperfusion. In some experiments, IL-12 was neutralized with antibody
      administered intravenously. RESULTS: Wild-type mice demonstrated rapid activation
      of STAT4 in liver after ischemia/reperfusion, which mirrored hepatic protein
      expression of IL-12. Interestingly, STAT4-deficient mice were indistinguishable
      from wild-type mice in their response to hepatic ischemia reperfusion. No
      differences were observed in serum levels of tumor necrosis factor alpha (TNF
      alpha), liver accumulation of neutrophils, or hepatocellular injury. However,
      blockade of endogenous IL-12 significantly reduced these parameters in STAT4
      knockout mice. CONCLUSIONS: These data demonstrate that IL-12 promotes hepatic
      inflammation in a manner that is independent of STAT4 and implicate a novel
      mechanism for the pro-inflammatory effects of IL-12.

PMID- 11965048
TI  - Incidence of hyperacute rejection in pig-to-primate transplantation using organs
      from hDAF-transgenic donors.
AB  - BACKGROUND: Cynomolgus monkeys or baboons received under immunosuppression kidney
      or heart grafts from pigs transgenic for human decay-accelerating factor (hDAF)
      or from control pigs. Hyperacute rejection (HAR) is often difficult to
      differentiate from nonimmunological causes of organ or recipient dysfunction
      (NIC), and therefore, a thorough pathology review of all cases with 0-4 days
      survival (inclusive) was conducted. METHODS: Pathology slides were blinded and
      together with limited clinical data reviewed by two pathologists. After
      unblinding, data were compared with the original diagnosis made during the course
      of the program, and a final diagnosis was reached considering the complete
      clinical dataset. RESULTS: Life-supporting kidney transplantation was performed
      in 245 cynomolgus monkeys (234 hDAF, 11 controls), of which 102 cases had 0-4 day
      survival. None of the hDAF cases showed HAR, whereas this occurred in 27% of
      controls (P<10-6). Heterotopic heart transplantation was performed in 65 monkeys
      (57 hDAF, 8 controls), of which 41 cases had 0-4 day survival. HAR was observed
      in 7% of hDAF cases and in 57% of controls (P=0.002). Heterotopic heart
      transplantation in baboons was performed in 33 animals (28 hDAF, 5 controls), of
      which 15 cases had 0-4 day survival. HAR was observed in 11% of hDAF cases and in
      20% of controls. Sixteen baboons were subjected to orthotopic heart
      transplantation, all from hDAF donors, out of which eight survived 0-4 days. The
      incidence of HAR was 6%. CONCLUSIONS: In the largest series of pig-to-primate
      solid organ transplants performed thus far, the presence of the hDAF transgene
      fully prevents HAR of cynomolgus monkey kidney transplants and partially inhibits
      HAR of heart grafts in cynomolgus monkeys or baboons. The incidence of HAR in
      control grafts is significantly higher.

PMID- 11965049
TI  - Anti-alpha-fetoprotein imaging is useful for staging hepatoblastoma.
AB  - BACKGROUND: Liver transplantation (Tx) has become an alternative treatment of
      malignant childhood liver tumors, and the importance of careful
      pretransplantation evaluation has been emphasized. Anti-alpha-fetoprotein (AFP)
      imaging has been suggested for evaluation of adult patients with AFP-positive
      tumors. METHODS: Antibody imaging utilizing Tc-99 m-labeled monoclonal anti-AFP
      Fab' fragments was used to demonstrate pathologic uptake in hepatoblastoma (HB).
      RESULTS: Radical operation or liver Tx was not possible after four cycles of
      chemotherapy in a child with HB because of a single extrahepatic metastasis.
      Chemotherapy was continued, and reevaluation with anti-AFP imaging demonstrated a
      pathologic uptake only in the liver. Subsequently, a right liver lobe resection
      was performed. Along with a new rise in serum AFP, repeated anti-AFP imaging
      revealed active liver tumor but no metastases. A liver Tx was performed, and the
      child is well with a normal serum AFP level 18 months after the operation.
      CONCLUSION: This is the first case of pediatric HB in which anti-AFP imaging has
      been successfully used for patient management.

PMID- 11965050
TI  - Factors influencing T-lymphopoiesis after allogeneic hematopoietic cell
      transplantation.
AB  - In adult recipients of allogeneic hematopoietic cell transplants (HCT) studied at
      1 year after grafting, there was a significant correlation between the counts of
      T cell receptor excision circle (TREC)-containing CD4 T cells (presumed recent
      thymic emigrants) and the counts of total T cells (r=0.65, P<0.001). Thus, the
      reconstitution of CD4 T cell pool depends on T cell generation from hematopoietic
      stem cells (T-lymphopoiesis). We evaluated factors that could affect T
      lymphopoiesis. Low TREC-containing CD4 T cell counts were associated with older
      patient age (r=-0.41, P=0.01) but not with donor age, graft type (marrow vs.
      blood stem cells), CD34 cell dose, conditioning (with vs. without irradiation),
      acute graft-versus-host disease (aGVHD), or chronic graft-versus-host disease
      (cGVHD) in multivariate analysis. We conclude that patient age is the primary
      determinant of CD4 T-lymphopoiesis after allogeneic HCT.

PMID- 11965051
TI  - Is mycophenolate mofetil less safe than azathioprine in elderly renal transplant
      recipients?
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is a potent immunosuppressive agent that
      has been shown to be superior to azathioprine in preventing early acute rejection
      in the general renal transplant population. However, it is uncertain whether
      these benefits also apply to older renal transplant recipients, who are known to
      be more susceptible to infectious complications and have considerably lower rates
      of rejection and immunological graft loss. METHODS: A retrospective analysis was
      undertaken of all elderly (> or =55 years old) renal transplant recipients who
      underwent renal transplantation at the Princess Alexandra Hospital (1994-2000)
      and received either MMF (n=60) or azathioprine (n=55) in combination with
      prednisolone and cyclosporin. Data were analyzed on an intention-to-treat basis
      using a multivariate Cox proportional hazards model. RESULTS: The azathioprine-
      and MMF-treated groups were well matched at baseline with respect to demographic
      characteristics, end-stage renal failure causes and transplant characteristics.
      Compared with the MMF cohort, azathioprine-treated patients experienced a shorter
      time to first rejection [hazard ratio (HR) 4.47, 95% CI 1.53-13.1, P<0.01].
      However, azathioprine-treated patients were also less likely to develop
      opportunistic infections (HR 0.11, 95% CI 0.03-0.41, P=0.001). No differences
      were observed between the two groups with respect to hospitalization rates,
      intensive care admissions, hematological complications, or posttransplant
      malignancies. Actuarial 2-year survival rates for the azathioprine- and MMF
      treated patients were 100 and 87%, respectively (P<0.001). The principal cause of
      death in the MMF cohort was infection. Using a multivariate Cox regression
      analysis of patient survival, an adjusted hazard ratio of 0.01 (95% CI 0.001
      0.08, P=0.001) was calculated in favor of azathioprine. Overall graft survival
      also tended to be better in patients receiving azathioprine (HR 0.27, 95% CI 0.06
      1.33, P=0.11), CONCLUSIONS: In elderly renal transplant recipients, the
      combination of MMF, cyclosporin, and prednisolone appears to result in a worse
      outcome compared with the less potent combination of azathioprine, cyclosporin,
      and prednisolone. Future prospective studies need to specifically evaluate the
      risk/benefit ratios of newer, more potent immunosuppressive protocols, such as
      MMF-based regimens, in this important and sizeable patient subgroup.

PMID- 11965052
TI  - Right liver graft without middle hepatic vein reconstruction from a living donor.
AB  - A case of adult-to-adult, living-donor liver transplantation using a right liver
      graft is described. In the donor operation, when the middle hepatic vein (MHV)
      was clamped after hepatic transection, reversed flow was detected in MHV
      tributaries by intraoperative color Doppler ultrasonography. Regurgitated flow in
      the clamped inferior right hepatic vein was also demonstrated. Portal flow
      remained hepatopetal during the procedure. Based on these ultrasonographic
      findings, neither the MHV tributaries nor the inferior right hepatic vein was
      reconstructed.

PMID- 11965053
TI  - Successful retransplantation after renal allograft loss to polyoma virus
      interstitial nephritis.
AB  - BACKGROUND: Although polyoma virus infection is being increasingly recognized as
      a cause of renal allograft dysfunction and failure, the risk of polyoma
      recurrence in a subsequent transplant is unknown. We present the first reported
      case of successful retransplantation after polyoma virus-induced renal allograft
      loss. CASE REPORT: A 40-year-old Caucasian woman received a cadaveric kidney
      transplant. Baseline immunosuppression included corticosteroids, mycophenolate
      mofetil, and tacrolimus. Her post-transplant clinical course was complicated by
      an early acute rejection episode on posttransplant day (PTD) 6, that warranted
      treatment with OKT3. A biopsy performed on PTD 154 to evaluate a rise in
      creatinine revealed polyoma virus interstitial nephritis. Despite reduction in
      immunosuppression, the renal function progressively worsened and dialysis was
      initiated by PTD 160, followed by transplant nephrectomy on PTD 184. Four months
      later, she received a living related kidney from her sister. Immunosuppression
      was initiated with prednisone, azathioprine, and tacrolimus. She had immediate
      graft function with a decrease in serum creatinine from 12.8 to 1.1 mg/dl. Three
      and one-half years after her second renal transplant, her allograft functions
      well, with a serum creatinine of 1 mg/dl. Both quantitative and qualitative
      assays of blood and urine (by PCR) remain negative for BK virus, indicating the
      absence of virus reactivation. CONCLUSION: Judicious retransplantation should be
      considered as a therapeutic option in the management of polyoma virus induced
      graft failure. Previous graft loss secondary to polyoma virus infection is not a
      contraindication to retransplantation.

PMID- 11965055
TI  - Secondary amyloidosis detected in a patient with cystic fibrosis after undergoing
      lung transplantation.

PMID- 11965054
TI  - Anti-CD25 monoclonal antibody coverage allows for calcineurin inhibitor "holiday"
      in solid organ transplant patients with acute renal dysfunction.
AB  - BACKGROUND: Solid organ transplant (Tx) patients on calcineurin inhibitors (CNI)
      can develop acute renal dysfunction (ARD), which could be improved by reducing or
      withholding ("holiday") CNI dose. METHODS: We used anti-CD25 monoclonal
      antibodies to prevent acute rejection in 11 adult Tx patients (7 heart, 2 liver,
      2 heart-renal Tx), requiring a CNI "holiday" because of 15 events of ARD after
      the initial postTx hospitalization. An event of ARD was defined as an increase in
      serum creatinine (Scr)>25% vs. baseline. The CNI "holiday" was implemented until
      Scr had decreased to baseline. Basiliximab was used in 7 patients (11 events),
      and daclizumab was used in 4 patients (4 events). RESULTS: The CNI "holiday" was
      implemented over 21+/-51 days. Anti-CD25 mAb were well tolerated with no episodes
      of acute rejection. Scr (micromol/liter) increased from 145+/-48 to 301+/-92
      (P<0.0001), and decreased to 143+/-55 with the CNI "holiday." CONCLUSIONS: Our
      results suggest that a CNI "holiday" may improve ARD after solid organ Tx without
      rejection under anti-CD25 mAb coverage.

PMID- 11965082
TI  - [Facts, fakes and "biblio". Do internists still have something to learn about
      dexfenfluramine?].

PMID- 11965084
TI  - [Diagnosis and treatment of malignant bone fibrohistiocytoma].
AB  - Malignant fibrous histiocytoma (MFH) and giant cells sarcoma arise from fibrous
      tissue and histiocytic cells evenly distributed in all age group, except children
      much less common than osteosarcoma and chondrosarcoma. They most commonly
      localize in the major long bones (femur, tibia, humerus) and in pelvis. Pain and
      sometimes swelling are the most frequent symptoms but pathologic fractures are
      rather common. Medical imaging shows a purely osteolytic tumor centrally or
      eccentrically located, ill defined with a permeative or even moth eaten patterns.
      Periosteal reaction is scarce or absent. Osteogenic reaction or tumor
      calcifications are absent. Outcome was historically better than those of
      osteosarcoma but hangs on the grading of tumors; low grade sarcoma have a
      regional evolution while high grade malignant histiocytofibroma are threatened
      with metastases. Therapy must be adapted to the histological grading and the
      extent of the illness. Low grade localized MFH are best treated by wide
      resection. High grade MFH are preferentially treated by a comprehensive
      multidisciplinary approach with preoperative chemotherapy including high dose
      methotrexate, wide resection and postoperative chemotherapy. With such a
      treatment, nearly 80% of patients seen with localized tumor of the limb can be
      cured and keep a functional limb.

PMID- 11965083
TI  - Fenfluramines, idiopathic pulmonary primary hypertension and cardiac valve
      disorders: facts and artifacts.
AB  - The fenfluramines saga began in 1963 and ended in 1997. Fenfluramines are
      anorexigenic agents recommended, in April 1996, for the long-term treatment of
      obesity in USA, before being suddenly withdrawn from the market in September
      1997. Over 34 years, about 60 million people were exposed to these drugs
      worldwide, mainly in Europe. The aim of this critical review is not to attempt to
      rehabilitate these appetite suppressants but to launch a plea for a more rational
      and rigorous approach to what might be called objective medical knowledge.
      Idiopathic primary pulmonary hypertension and cardiac valve disorders which have
      been both associated with fenfluramines have in common many puzzling features.
      The metamorphosis of facts into artifacts is only a hypothesis, but seems
      conceivable from a scientific point of view. Medicine is not only an art, it is
      also a science, which, like the others, implies adhesion to certain fundamental
      rules, such as refutation or verification of all experimental results by rigorous
      and standardized methods, before considering them as established facts. Firstly,
      a single study, moreover a case-control study like the International Primary
      Pulmonary Hypertension Study, is not sufficient to establish a causal
      relationship between exposure to appetite-suppressants and idiopathic pulmonary
      hypertension, because of the numerous biases which characterize even the best
      analytical research. Secondly, Doppler-echocardiography cannot be considered as a
      laboratory test, because of the poor interoperator reproducibility observed in
      obese patients. The use of this technique in pharmaco-epidemiology implies
      standardized procedures concerning not only reading data, but also their
      acquisition, because of possible uncontrolled interactions between sonographers,
      patients and sophisticated machines. In the case of the fenfluramines saga,
      numerous methodological artifacts concerning acquisition, processing and
      interpretation of epidemiologic and echocardiographic data might have contributed
      to distortion of reality. Let us recall how Webster's dictionary defines
      artifact: "a spurious observation or result arising from preparatory or
      investigative procedures or any feature that is not naturally present but is a
      product of an extrinsic agent, method, or the like".

PMID- 11965086
TI  - [Genetic hemochromatosis and blood donation].

PMID- 11965085
TI  - [Victims of general crimes. Prospective and longitudinal assessment of
      psychological injuries].
AB  - OBJECTIVE: The aim of this study was to assess the relations between acute
      psychological injury, particularly peritraumatic dissociation, and early
      development of posttraumatic stress disorder in victims of violence. METHODS:
      Thirty-five subjects were prospectively assessed in an emergency department,
      within 24 hours of the trauma, for acute dissociative experiences with the
      Peritraumatic Dissociative Experiences Questionnaire (PDEQ). All of them were
      followed longitudinally to assess post traumatic stress disorder (PTSD) 5 weeks
      after with the Clinician-administered PTSD scale (CAPS) and the Impact of event
      scale (IES). RESULTS: Of the 35 victims 10 (28%) were diagnosed with a
      posttraumatic stress disorder at 5 weeks. Among PTSD subjects mean PDEQ scores
      were significantly higher (3+/-1.1) than in those without PTSD (2.3+/-0.7)
      (t=2.24, df=33, p=0.029). The PTSD subjects reported more "out of body
      experience" (p=0.015) and more "sense of body distorsion" (p=0.03) than non PTSD
      subjects. CONCLUSION: High levels of peritraumatic dissociation following violent
      assault are risk factors for early posttraumatic stress disorder. Psychological
      assessment of acute traumatic dissociative experiences must be included in
      emergency departments.

PMID- 11965087
TI  - [Dermatomyositis and polymyositis: clinical aspects and treatment].
AB  - Dermatomyositis and polymyositis are the two major idiopathic inflammatory
      myopathies. The Bohan and Peter's criteria are still useful despite the probably
      different pathogenesis of the two myopathies. Cutaneous manifestations of
      dermatomyositis include heliotrope rash and Gottron's papules. The heliotrope
      rash, with or without edema, in a distribution involving periorbital skin is very
      suggestive of the diagnosis. Papules may be found overlying the "kneedle" of the
      hand or the elbows, knees, feet. Periungueal erythema with telangiectasis were
      characteristic but not pathognomonic. Scalp involvement is common. Skin lesions
      of dermatomyositis may precede the development of the myopathy and may persist
      after the control of the myositis. Some patients have an amyopathic
      dermatomyositis with normal muscle-enzyme, magnetic resonance scan and muscle
      biopsy. Muscle disease affects the proximal muscles, is generally symmetrical and
      symptoms are fatigue, weakness and sometimes myalgia. Proximal dysphagia reflects
      an involvement of striated muscle of the pharynx or proximal esophagus.
      Camptocormia reflects a severe involvement of paravertebral muscle. Other
      systemic features may be seen: pulmonary involvement (mostly interstitial
      pneumonitis and hypoventilation), arthralgias or arthritis, cardiac involvement,
      vasculatis and calcinosis particularly in children or adolescents with
      dermatomyositis. Malignant disease is associated with idiopathic inflammatory
      myopathies with a frequency of approximatively 10 to 15% in dermatomyositis and 5
      to 10% in polymyositis and is strongly correlated with age, more than 50% of the
      patient over 65 years old were found to have a cancer. In the absence of
      malignant disease, the mainstay therapy for dermatomyositis and polymyositis is
      systemic corticosteroids (mostly 1mg/kg). In the lake of response or high dose
      dependance, intravenous immunoglobulins or immunosuppressive drugs like
      methotrexate or azathioprine may be discuss. Cyclophosphamide show some
      effectiveness in interstitial pneumonitis. Cyclosporin might be effective in
      children, less in adults. The efficacy of tacrolimus, mycophenolate mofetil,
      leflunomide and anti-TNF therapy need some prospective studies to determine if
      there are of value in idiopathic inflammatory myositis.

PMID- 11965088
TI  - [Histological data in inflammatory myositis].
AB  - Inflammatory muscular diseases of adult and child consist of dermatomyositis
      (DM), polymyositis (PM) and inclusion body myositis (IBM). Muscular biopsy takes
      a seminal place in their diagnosis, through analysis of the topography and
      clustering of individual histological lesions: endomysial, perimysial and
      perivascular inflammation, muscular necrosis with regeneration, fibre
      modifications, fibrosis, micro-angiopathy. They can be associated with collagen
      diseases or malignant tumors that usually precede them. IBM seems somewhat apart
      among inflammatory myopathies, being characterised by the association of
      neurogenic and myogenic features and the presence of vacuoles containing
      filaments with an accumulation of proteins previously reported in Alzheimer's
      disease (beta amyloid protein, tau, ubiquitin,.). Inflammation is of various
      intensity, lacking in familial IBM (hereditary inclusion body myopathy) that
      otherwise shares the same histologic characteristics as sporadic forms. Other
      inflammatory muscular diseases: focal myositis, eosinophilic polymyositis, are
      less frequent. Macrophagic myofasciitis, viral myositis and drug induced myositis
      are discussed in other articles.

PMID- 11965089
TI  - [Behcet's disease associated with Crohn's disease].
AB  - INTRODUCTION: The association of Behcet's disease and of Crohn's disease is
      exceptional, and raises a nosological problem. CASE REPORT: A 24 year-old female
      developed since 1996 chronic diarrhea, abdominal pain, recurrent oral and genital
      ulcer and polyarthralgia. Endoscopic colonoscopy examination showed a diffuse
      colitis. Histological examination revealed epitheloid granuloma without
      vasculitis compatible with a Crohn's disease. The patient was treated with oral
      prednisone (1mg/kg/day). In November 1998, she was admitted for diarrhea. Many
      pseudofolliculitis lesions, uveitis and positive pathergy test were noted. The
      HLA was B 51. The diagnosis of Crohn's disease associated with Behcet's disease
      was made. She was treated with high doses of prednisone (1mg/kg/day and 6 monthly
      intravenous pulses of cyclophosphamide). Skin lesions and diarrhea improved
      within few days, and cleared completely within five months. Presently, the
      patient remains clinically free of disease. CONCLUSION: While being of different
      pathogenic origin, Behcet's disease and Crohn's disease may coexist within one
      and the same patient and cause diagnostic and therapeutic problems.

PMID- 11965090
TI  - [Hypocalcemic dilated cardiomyopathy: rare cause of heart failure].
AB  - Hypocalcemic dilated cardiomyopathy is a rare cause of heart failure in adults.
      We report a case in a 19-year-old woman who developed congestive heart failure
      induced by severe chronic hypocalcemia disclosing primary hypoparathyroidism.
      Complete regression of the clinical signs was achieved with vitamin-calcium
      treatment, but left ventricular systolic dysfunction persisted eight months after
      treatment.

PMID- 11965091
TI  - Methadone treatment: common questions, a common answer.

PMID- 11965092
TI  - [Prevalence of HBV and HCV infections and incidence of HCV infection after 3, 6
      and 12 months detention in La Sante prison, Paris].
AB  - The concentration of a marginal population (35% drug addicts) in prisons
      necessitates systematic and rigorous screening for hepatitis B and hepatitis C in
      subjects at risk. In June 1998, a screening program was initiated to determine
      the prevalence of HBV and HBC infections in prisoners and to determine the
      incidence after 3, 6 and 12 months detention. The screening program was proposed
      to 900 prisoners in a Paris prison (Maison d'arret de Paris-La Sante) from June 3
      to November 10, 1998. The program included hepatitis B and hepatitis C serology
      at incarceration. For prisoners who were seronegative for HCV at incarceration, a
      new HCV serology was proposed after 3, 6 and 12 months detention. It was
      postulated that HCV contamination could occur during incarceration (syringe
      sharing, tattooing). After one year of incarceration, no seroconversions for HCV
      were observed among the prisoners participating in this study. These findings
      should be interpreted with caution due to the particular detention conditions at
      the prison involved, raising important methodology interrogations concerning this
      type of survey.

PMID- 11965093
TI  - [Changes in high-dose buprenorphine maintenance therapy at the Fleury-Merogis
      (France) prison since 1996].
AB  - Since the law of January 1994, the ministry of Health is responsible for inmate
      health in France. This law created medical wards inside French prisons by
      conventions between hospitals and prisons. Since July 1995, Fleury-Merogis state
      prison is linked to the Sud-Francilien Hospital. During the last few years, more
      and more IV drug users have been incarcerated and the number of infectious
      diseases has increased (AIDS, hepatitis C and B). Risk behavior is rather
      frequent and it has become a major concern of public authorities to fight this
      evolution. Prisons are part of structures having to take care of IV drug users. A
      few months after the authorization of buprenorphine in France (March 1996), the
      ministry of Health decided to give access to this treatment for incarcerated IV
      drug users. The aim of this study is to present the evolution of maintenance
      medication by high dose buprenorphine in a big state-prison and to explain the
      difficulties we have to face. The aim of this study was also to present how this
      treatment can contribute to reducing infectious risks. Surveying prescription is
      under the control of the Pharmacy since 1995. We have studied since 1996 the
      number of prescriptions, segregating initialized inside the prison and
      prescriptions continued. We have also studied and evaluated the number of
      psychotropic drugs for each prescription since 1996 in "two test buildings".
      Evolution of self mutilations and reducing infectious risks support measures have
      also been studied.

PMID- 11965094
TI  - [Changes in pharmacists practices (1996 - 2000) related to harm reduction policy
      (condoms, injecting equipment, methylmorphine) and maintenance therapy delivery
      (buprenorphine, methadone)].
AB  - AIMS: To measure pharmacists involvement in harm reduction programs and in
      delivery of maintenance therapies in order to estimate their contribution to the
      new public health policy. METHOD: A longitudinal study was conducted among 327
      pharmacies located in the southern suburban area of Paris (28 communities) using
      a standardized questionnaire. RESULTS: The response rate was 95% in 1996 and 92%
      in 2000. The number of condoms offered to intravenous drug users (IDU) decreased
      dramatically from 99% to 24% while delivered units decreased from 857 to 566 per
      day for needles and from 1200 to 760 per month per pharmacy for methylmorphine
      tablets (14.93 mg/tablet). Pharmacists delivered injecting equipment to some of
      their patients under opiate treatment: methylmorphine 19%, buprenorphine 35%,
      methadone 14%. Their contribution to the local healthcare network on addiction
      decreased from 38% to 20%. Nevertheless, the pharmacists attitude towards the IDU
      and public health policy was found to be improving with problems being mentioned
      for 62% of the cases in 1996 and for 16% in 2000. CONCLUSION: Pharmacists are
      rapidly and intensively changing their practices and are discovering a new
      comprehensive relationship with IDU. Better pharmacist involvement is associated
      with a shift in local healthcare network concentration, reinforcing the general
      practitioner-pharmacist partnership.

PMID- 11965095
TI  - [Withdrawal syndromes of newborns of pregnant drug abusers maintained under
      methadone or high-dose buprenorphine: 246 cases].
AB  - Perinatal prognosis of pregnant drug abusers is better with intensive prenatal
      care and substitution maintenance programs. There is a large body of data in the
      literature on methadone (MTD), but very little on high-dose buprenorphine (HDB).
      The objective of this study was to compare 2 groups of pregnant women maintained
      on MTD or HDB for perinatal events. STUDY DESIGN: Prospective multicentric study;
      all neonates (NN) whose mothers has been maintained during pregnancy on MTD or
      HDB were included by 34 French perinatal centers with specialized staff for care
      of these pregnant drug abusers. RESULTS: Two hundred and forty-six pregnant women
      were included: 93 (38%) MTD and 153 (62%) HDB. Social and perinatal data,
      prenatal care and factors correlated with poor prenatal care are reported. Forty
      six percent of the pregnant women had good prenatal care; 88% had peridural
      analgesia; mean birthweight=2838g; mean gestational age=38.7 weeks;
      prematurity<37 weeks=13; intra-uterine growth retardation=32%. Sixty-five percent
      neonates had withdrawal neonatal syndrome (WNNS) at a mean age of beginning at
      H40, mean highest Lipsitz score was 8.2 at H78. Half of the neonates with WNNS
      received treatment, mainly with morphine chlorhydrate. Neonatal mortality was
      0/246. Discharge of the neonates was 60% with their father and their mother, and
      32% with their mother alone; 4% were placed in foster homes by judicial decision.
      The only statistically significant differences between the MTD and HDB groups
      were: maintenance program was more frequently initiated before this pregnancy for
      the HDB vs MTD group (p<0.03); MTD maintenance was more often supervised by
      maintenance specialized centers and HDB by general practitioners (p<0.001);
      prematurity was 18% for MTD group vs 9% for HDB group (p<0.04); mean age of
      maximum Lipsitz score was H92 for MTD group vs H70 for HDB group (p<0.001).
      CONCLUSIONS: The perinatal medical and social prognosis of these 246 pregnant
      drug abusers and of their neonates appeared to be improved by the specialized
      prenatal care, comparatively with literature data. Perinatal impact of
      substitution program during pregnancy would be similar with MTD or HDB.

PMID- 11965096
TI  - [Sport practice and cannabis consumption in a representative sample of French
      high school adolescents].
AB  - PURPOSE: - To assess the association between cannabis consumption and sport
      practice. METHODS: We randomised a representative sample of 1,506 girls and 1,420
      boys from the third to the last year of school in the French Midi-Pyrenees
      region, excluding classes reserved for children practising high level sport.
      Information was collected by self-answer questionnaire. RESULTS: More than 90% of
      boys and 70% of girls declared they practised sport outside physical education at
      school (athletic students). Among boys, sport practice mainly concerned
      activities in clubs or competitions (respectively 66% and 60%, against 35% and
      27% among girls; p<0.001). Twenty-eight percents of boys and 19% of girls
      declared they had consumed cannabis (at least occasionnally, during or outside
      sport). Among athletic students, such potential consumption concerned 28.6% of
      boys and 19.6% of girls (p<0.001). Moreover, 1.2% of athletic students (n=7)
      declared they had already consumed cannabis during the practice sport with clubs
      or competitions. Among boys, this potential consumption increased with age, was
      lower among non-athletic students and the most athletic students, but was highest
      among those practising an individual "X-treme" sport (50% in this group versus
      26% among athletes practising collective or non- "X-treme" sport; p<0.001).
      Potential cannabis consumption was also highest among athletes who declared they
      practiced sport for seeking emotions, who did not practise sport for health
      benefits but who considered that sport could involve taking risks. CONCLUSION: It
      seems more important to consider how sport is practised rather than its intensity
      when assessing the association between sport and cannabis consumption. Indeed,
      sport appears to be more favourable for cannabis consumption when associated with
      ideas of emotion and risk and when practised outside of an organisation.

PMID- 11965097
TI  - [Sports, use of performance enhancing drugs and addiction. A conceptual and
      epidemiological review].
AB  - BACKGROUND: Both the general public and non-sports medicine health professionals
      have recently been made aware of a large use of performance enhancing drugs among
      sports practicing subjects. It has been suggested that this behavior is similar
      to that of substance dependence. Also some have reported that practice of a sport
      could be in itself an addictive behavior. OBJECTIVE: The main objective was to
      address the following question: is performance enhancing drug use in sports an
      addictive behavior? Methodology. We first reviewed the definition of performance
      enhancing drug use in sports and the diagnostic criteria of substance dependence
      as they are currently accepted and attempted to determine a possible common
      factor. Secondly we reviewed epidemiological data from the literature according
      to three approaches: RESULTS: Use of performance enhancing drugs is an important
      and increasing phenomenon among adolescents. It is sometimes associated to risk
      taking behaviors for health (syringe use and sharing). Competition participants
      are at increased risk (up to 20% according to some authors) and some substances
      (anabolic steroids) are also used by non-sports practicing individuals. It has
      not been shown that sports practicing subjects were more at risk of using
      addictive substances compared to non-sports practicing subjects. It is not
      established that practice of a sport is by itself a risk factor for substance
      use. However, it could be that a sub-group of individuals that practice certain
      types of sports in an intensive way, that use both performance enhancing drugs
      and addictive substances and that engage in health risk taking behaviors have an
      increased risk for developing a dependence syndrome to both addictive and
      performance enhancing drugs. This sub-group is even more at risk because some
      performance enhancing drugs (anabolic steroids) could increase the risk for
      occurrence of a substance dependence syndrome through neurobiological actions.
      Yet, the few available clinical studies show that at most only half of regular
      users actually meet criteria for dependence. Also, one study has reported an
      overrepresentation of sports professionals among patients seeking treatment for
      heroin addiction. CONCLUSION: The large majority of sports practicing subjects
      have no dependence to either performance enhancing or addictive drugs. However, a
      subgroup of individuals that practice sports intensely and makes use of both
      addictive and performance enhancing drugs appear to be at increased risk for
      developing a substance dependence syndrome.

PMID- 11965098
TI  - Slow metabolism and long half life of methadone in a patient with lung cancer and
      cirrhosis.
AB  - In a patient on methadone maintenance treatment, admitted for lung cancer
      suspicion, a slight decrease in pain dose response to morphine have necessitated
      adjustments of methadone treatment founded on clinical check-up and methadone
      assay. Plasma methadone concentrations were 4 fold higher than mean plasma
      concentration for control population at the same dose. Half-life was above 70
      hours and clearance and metabolic index were strongly decreased. In this patient,
      daily dose methadone occurred in progressive accumulation and neuro-physiological
      tolerance without clinical incidence, except decrease in morphine effectiveness
      compared to our knowledge. Cancer, cirrhosis and adjuvant therapy contributions
      (fluconazole, omeprazole) to this original methadone kinetic are discussed.
      Methadone and morphine dose clinical adjustments are described. However, the main
      objective of this case report is focused on plasma methadone assay contribution
      to therapeutic adjustment of the interval dose in a single patient with a complex
      clinical situation.

PMID- 11965099
TI  - [Interview with Jean-Claude Maleval: specificity of drug use in psychotic
      patients].

PMID- 11965100
TI  - [Persistent injecting practices in subjects on methadone or buprenorphine
      maintenance therapy. A study of 600 cases].
AB  - A descriptive study conducted at the Louis-Harris Institute enrolled 600 patients
      taking methadone or buprenorphine (Subutex((R))) substitution therapy who were
      followed by general practitioners or specialists working in specialized clinics.
      The objective was to look for factors correlated with persistent injecting
      practices. Several factors were found to be statistically correlated with
      persistent injecting practices: impulsiveness, depressive state, and relative
      under-dosing (first daily or globally) in patients on Subutex((R)). Considering
      these factors, a better psychosocial impact could be achieved by providing
      sufficient attention to anxious or depressive states aggravating the effects of
      impulsiveness (co-usage of certain substances, psychotonics, search for certain
      psychopathological states) and paying special attention to the more impulsive
      subjects. Optimal coverage with earlier orientation to appropriate psychiatric
      care requires a team effort including educators, social workers and healthcare
      professionals. Such measures must be conducted within the framework of good
      clinical practices to establish a coherent multidisciplinary healthcare scheme
      which should help eliminate this source of more or less overt somatic
      complications. Such good clinical practice could also facilitate safe extinction
      of the conditioning inferred by addicted behavior (persistent injecting
      practices) which could persist only a few months after the end of the stimulus
      (cessation of emotional pain).

PMID- 11965101
TI  - [Is sudden sensorineural hearing loss a therapeutic emergency? Early results in a
      prospective cohort of 136 patients].
AB  - Idiopathic sudden sensorineural hearing loss is one of the most controversial
      issues in otology. A prospective cohort study including 136 sudden hearing losses
      seen at the ENT emergency referral center of Lariboisiere Hospital during an 18
      month period was conducted. Patients were hospitalized and a corticotherapy
      course was administered, eventually associated with an antiviral treatment, low
      molecular weight dextran or sedative. At the end of the 5-day hospitalization,
      74% of the patients had recovered, at least partially, with a mean gain of 22 dB.
      The outcome was considered satisfactory, i.e. superior to 50% of the initial
      loss, in 30% of the patients. After 1 month, 86% of the patients recovered at
      least partially with a mean gain of 30 dB. The outcome was considered
      satisfactory in 44% of the patients. A prognosis analysis showed that vertigo,
      age of the patient and anacusis are pejorative factors. Ascending audiogram
      shapes seem to involve a better prognosis. The therapeutic delay is not
      correlated with the quality of the outcome, which questions the classical notion
      of therapeutic emergency.

PMID- 11965102
TI  - [Laryngeal Preservation with Induction Chemotherapy. Experience of two GETTEC
      Centers, Between 1985 and 1995].
AB  - This is a retrospective study of laryngeal preservation in endolaryngeal cancer
      with induction chemotherapy and radiotherapy for good responders. Between 1985
      and 1995, 104 patients were treated in Institut Gustave Roussy (87 patients) and
      in Limoges (17 patients). The overall survival for the whole population was 76%
      and 69% at 3 and 5 years respectively, with a 36% rate of laryngeal preservation.
      In this retrospective series of patients, the single prognostic factor affecting
      survival was arytenoid mobility before treatment (66% and 55% at 3 years vs 85%
      and 82% at 5 years; p<0.004). Loco-regional failures were higher (33% vs 15%,
      p<0.03), and laryngeal preservation was lower (18% vs 51%) among patients with a
      fixed arytenoid (49 pts), compared with patients with a non fixed arytenoid (55
      pts) ). The percentages of patients with a fixed arytenoid could explain the
      conflicting results of the two randomized studies of laryngeal preservation in
      laryngeal cancer.

PMID- 11965103
TI  - [Carbon dioxide laser transoral microsurgery for glottic carcinoma in situ].
AB  - OBJECTIVE: To evaluate the oncologic results of glottic carcinoma in situ (CIS)
      treated with transoral carbon dioxide laser microsurgery. METHODS: A
      retrospective review of 12 patients with glottic CIS previously untreated,
      treated with carbon dioxide laser transoral microsurgery between January 1990 and
      December 1999 was conducted. RESULTS: Initial and ultimate local control rates
      were 75%, and 100%, respectively. Three local failures occurred: two glottic CIS
      were treated by carbon dioxide laser transoral microsurgery, one squamous cell
      glottic carcinoma was treated by supracricoid partial laryngectomy with
      cricohyoidoepiglottopexy. The ultimate rate of laryngeal preservation rate was
      100%. CONCLUSIONS: Based on the material of this study, recommended treatment for
      glottic CIS should be carbon dioxide laser transoral microsurgery. Difficulties
      in endoscopic exposure of the larynx is a contraindication. Further studies are
      necessary to confirm these preliminary results.

PMID- 11965104
TI  - [15 years experience with microvascular free tissue transfert for repair of head
      and neck cancer defects].
AB  - We present the modalities and results obtained with free flap reconstruction of
      head and neck cancers defects. This retrospective review of 165 free transfers
      performed between 1984 and 1999 included 89 radial forearm flaps (54%), 38
      latissimus dorsi flaps (23%), 28 osteomyocutaneous flaps (17%), 6 omentum flaps
      (4%), 2 jejunum flaps, and 2 cutaneous scapular flaps. Indications were
      orobuccopharynx (34%), hypopharynx (24%), mandible (17%), craniofacial (15%) and
      skin (10%) defects. Flap failure rate was 9%. Reconstruction of a radiated site
      was a statistically significant indicator of flap failure. Four types of free
      flaps were preferred for reconstruction of head and neck cancer defects. The
      radial forearm flap was used as a lap flap for the orobuccopharynx, the tubuled
      radial forearm flap for reconstruction of the digestive tract after total
      pharyngolaryngectomy, the osteomyocutaneous free fibular flap for
      pelvimandibulectomy, especially for the anterior arch, the latissimus dorsi flap
      to fill craniofacial defects, and the free omentum flap for craniofacial
      complications after radiotherapy.

PMID- 11965105
TI  - [Cervical lymph node involvement in carcinomas of the mobile tongue in Tunisia.
      Retrospective study of 135 cases].
AB  - OBJECTIVE: To report the profile of histologic cervical nodes involvement
      associated with mobile tongue squamous cell carcinoma. PATIENTS AND METHODS: Our
      retrospective study concerned patients treated from 1978 to 1998 by cervical neck
      dissection for mobile tongue carcinoma. RESULTS: A population of 135 patients (90
      M/45 F, sex-ratio 2) with a 53.5 mean age (19 to 75) is analyzed. Clinical
      palpable nodes were present in 68 cases (50%) mainly submental-submaxillar (54).
      Histologic examination showed a node involvement in 54 cases without (32 cases)
      or with capsular rupture (22 cases) mainly in the jugulo-carotidian chain
      (46/54). Among the 67 clinically N0 patients collected after 1990, 22 patients
      (33%) exhibited an histological involvement vs 32/68 (47%) for the group
      presenting palpable cervical nodes for the whole period. Histologic node
      involvement seemed to be linked to the clinical status, node size and TNM stage.
      CONCLUSION: Cervical lymph node treatment needs to be systematic in mobile tongue
      carcinoma. The probability of histologic involvement is linked to the loco
      regional extent of disease and influences the prognosis. In N0 patients, neck
      dissection is required because of the frequency of histological involvement,
      particularly when loss to follow-up may be expected.

PMID- 11965106
TI  - [Cervical osteophytes and ENT disease: three surgery cases].
AB  - Vertebral cervical hyperostosis is frequent in the general population but is
      rarely symptomatic. Dysphagia is the most frequently encountered symptom. We
      report three cases of cervical hyperostosis leading to ENT symptoms. Two patients
      had bilateral laryngeal paralysis, rarely described in the literature. These
      three cases were treated surgically.

PMID- 11965107
TI  - [How to treat a thyroid adenocarcinoma inside a branchial cyst].
AB  - The authors reported three cases of branchial cycts containing a thyroid
      adenocarcinoma. This rare condition imposed a search for the primary tumor. All
      complementary investigations remained negative as in the few cases reported in
      the medical literature. A loboisthmectomy for one and a total thyroidectomy for
      the two others, with cervical recurential neck dissection for all was carried
      out. Histological examination of the operative specimen after total blocking in
      paraffin helped discover microscopic foci of papillary carcinoma in the thyroid
      gland. These data justified this therapeutic attitude because the nature of the
      adenocarcinoma found in the branchial cyst is likely to be metastatic.

PMID- 11965112
TI  - [Corneal stromal changes after LASIK].
AB  - PURPOSE: To assess stromal modifications after laser in situ keratomileusis
      (LASIK) for myopia using in vivo confocal microscopy. METHODS: Thirteen eyes from
      10 patients were examined before surgery and at days 8 and 30 after surgery using
      an in vivo confocal microscope coupled with a Z-Scan system. Stromal
      morphological changes, keratocyte density, flap thickness, and subclinical haze
      were evaluated and compared at different time points. RESULTS: Microfolds at the
      Bowman's layer were found in 55%, eyes as well as variable reflectivity particles
      located at the interface level in all postoperative examined eyes. The mean flap
      and activated-cell area thicknesses were respectively, 101+/-28 micrometer and
      50.5+/-14 micrometer with a significant negative correlation (r=-0.89, p=0.01).
      The intensity of the added peak (47.3+/-8.6% scattered light), corresponding to
      the subclinical haze, as measured by Z-Scan, was also negatively correlated with
      the flap thickness (r=-0.89, p=0.01). CONCLUSION: This study confirms the
      presence of microfolds and particles at the interface level as subclinical
      complications. Evaluating the keratocytic activation by confocal microscopy can
      lead to a better understanding of corneal wound healing after LASIK and can help
      to improve the techniques. The flap thickness seems to be involved in the
      cellular activation induced by LASIK.

PMID- 11965113
TI  - [Intraocular high pressure in thyroid-associated orbitopathy: physiopathological
      mechanisms, diagnosis, and management. Three case reports].
AB  - PURPOSE: To determine the mechanisms and treatment of ocular hypertension in
      patients with thyroid-associated orbitopathy and to differenciate it from
      glaucomatous damage. DESIGN: Three case reports. METHODS: Retrospective review of
      clinical findings, course, and treatment of the three patients. RESULTS: Elevated
      intraocular pressure in thyroid-associated orbitopathy observed in the three
      cases may involve different physiopathological abnormalities such as disturbances
      of venous circulation, compression by infiltrative muscles, and long
      corticosteroid use. In the first two cases, defects demonstrated in the perimetry
      are in consistent with glaucomatous damage. In the third case, visual field
      abnormalities may be compatible with a glaucomatous disease, but all defects
      resolved after therapy. Treatement was of the greatest difficulty for the three
      cases, associating antiglaucomatous medication, steroids, orbital radiotherapy,
      orbital decompression and extraocular muscle surgery. Intraocular pressure was
      controlled in all cases. CONCLUSIONS: Elevated intraocular pressure in thyroid
      associated orbitopathy is distinguished from glaucomatous disease by its
      physiopathological mechanisms, clinical course, visual field defects, and
      treatment. The management of this hypertension is closely related to the
      treatment of dysthyroid orbitopathy.

PMID- 11965114
TI  - [Efficacy of intravenous immunoglobulin in the treatment of Birdshot
      retinochoroiditis].
AB  - AIM: To evaluate the efficacy of intravenous immunoglobulin (IVIg) in the
      treatment of Birdshot retinochoroiditis. PATIENTS AND METHODS: Eighteen patients
      were followed-up prospectively in a total number of 37 patients recorded.
      Inclusion criteria were birdshot retinochoroiditis (BRC) according to the
      criteria defined by Ryan et al., and a decrease in visual acuity (VA). Efficacy
      was assessed by measurements of visual acuity and a decrease in inflammation and
      macular edema on fluorescein angiograms. RESULTS: Sex ratio=1, mean age was 51
      (range 29 to 72 years), HLA A29 was positive in 100% of the patients. VA at
      baseline was 0.6+/-2.4 (range 0.25 to 0.9). Angiography showed retinal vasculitis
      in 32 patients (86.48%) and cystoid macular edema in 16 patients (43.24%). IVIg
      was administered at a dosage of 0.4g/kg/d for 4 days then 0.6g/kg/d for 2 days
      every 4 weeks. Follow-up lasted a mean of 2.7+/-2.0 years (range, 4 months to 5.6
      years). Visual acuity of 35 out of 66 eyes (53%) increased by 2.6+/-1.5 (range 1
      to 5). In 19 eyes out of 66 (29%), VA remained stable and in 12 eyes out of 66
      (18%), VA decreased by -1.8+/-0.8 (ranges-4 to -1). Inflammation on fluorescein
      angiography improved in 17 patients (81%) and cystoid macular edema decreased in
      65% of the cases. Side effects were rare. Treatment was discontinued for side
      effects in only 3 patients. DISCUSSION: BRC is a chronique disease threatening
      vision. Treatments including systemic corticosteroids and cyclosporin A may
      result in severe long-term side effects. IVIg is well tolerated and may be
      therapeutic alternative for the treatment of BRC.

PMID- 11965115
TI  - [Comparison of PKR and LASIK for the treatment of low myopia: statistic study of
      refractive and optic results].
AB  - PATIENTS AND METHODS: We present a study which compares the refractive and
      optical results obtained after PKR and LASIK for the correction of low myopia
      without astigmatism. This retrospective study involved 729 patients. All
      operations performed by the same surgeon, and with the same excimer laser (a
      Technolas Keracor 117 C). Before operation, all patients had a spherical
      equivalent between -0.5 and -6.0 D and a cylinder less than -0.5 D. Two groups
      were formed according to the treatment used. Three postoperative examinations
      were done (the first between 3 and 7 days, the second between 1 and 3 months, and
      the third between 10 and 14 months). Refractive results: Our statisticaly study
      found no difference in the results obtained with the two techniques.
      COMPLICATIONS: The incidence of complications was similar for the two procedures,
      but those observed after LASIK are generally more serious. DISCUSSION: In this
      indication, the efficacy of PKR and LASIK is similar. CONCLUSION: PKR and LASIK
      are safe and efficacy for the treatment of low myopia. For these patients, the
      use of PKR of LASIK currently depends on the habit and preference of the surgeon.

PMID- 11965116
TI  - [Eye tension and open angle glaucoma in a Burkina Faso hospital].
AB  - PURPOSE: Studying the correlation between high intraocular pressure and glaucoma
      in black African patients. PATIENTS: and method: This study was retrospective and
      was based on 235 patients, i.e. 470 eyes examined from April 1993 to december
      1998 for elevated eye pressure, at the Sanou Souro hospital of Bobo-Dioulasso,
      Burkina Faso. For each subject, we noted visual acuity, age, sex, ocular tonus,
      the result of optical disc examination with the three-mirror glass, and the
      visual field examined with Goldmann perimetry. We excluded infants, young
      children, glaucoma with normal pressure, and patients with incomplete files.
      RESULTS: The patients were from 14 to 80 years old, with 18.3% 40 years-old or
      less. Male subjects predominated with a sex ratio of 2.26. Visual acuity was lost
      in 191 eyes (40.6%) and optic disk excavation was total in 214 eyes (45.5%). The
      Goldmann perimetry visual field test revealed defects in 390 eyes (83%). Ocular
      tension, optic disk excavation of the glaucomatous type, and visual field defects
      were associated in 70.4% of the cases. CONCLUSION: This study shows that in 70.4%
      of the cases, there was a correlation between high intraocular pressure and
      glaucoma. This glaucoma is acute and appears in young subjects. Efforts will be
      made to alert our population and detect glaucoma precociously.

PMID- 11965118
TI  - [Penetrating keratoplasty in ocular cicatricial pemphigoid].
AB  - PURPOSE: Ocular cicatricial pemphigoid (OCP) is a chronic progressive disease
      characterised by exacerbations of immunologically driven conjunctival
      inflammation. In the advanced stages of the disease, severe xerosis with
      mechanical factors may contribute to the development of blinding keratopathy. The
      authors report two cases of penetrating keratoplasty (PK) in patients with OCP
      and discuss the modalities of the surgical procedure for this particular disease.
      METHODS: Two patients with stage III OCP according to Foster's classification,
      underwent PK. Initial and final visual acuity, indications of PK, surgical
      procedure, postoperative therapy, and complications were recorded. RESULTS: For
      the first patient, after 3 months of follow-up, the graft is still clear, with a
      remarkable improvement in vision (3/10). For the second patient, however, graft
      rejection developed 15 days after the operation, complicated later by
      endophthalmitis, which was controlled with an antibiotic. DISCUSSION: The
      progression of ocular pemphigoid involves the filling of the conjunctival
      fornices, formation of symblepharon with lagophthalmos, and dry eye, from which
      blinding keratopathy can originate. A corticosteroid-based or immunosuppressant
      treatment blocks the progression of the fibrosis but does not get rid of
      palpebrale or corneal anomalies, making surgery necessary. This surgery generally
      gives disappointing results and should be planned when the disease is perfectly
      under control, during a lull in the disease so as to avoid reactivation of the
      fibrosis process. Reconstruction of the conjunctival fornices should also precede
      any corneal transplantation. CONCLUSION: These results indicate that PK may be
      performed to restore of sight in patients with advanced OCP after controlling the
      primary immunological process and aggressive treatment of the mechanical factors
      damaging the ocular surface.

PMID- 11965117
TI  - [Argon laser photocoagulation of circumscribed choroidal hemangiomas].
AB  - PURPOSE: Therapeutic retrospective results obtained after Argon laser
      photocoagulation of 17 circumscribed choroidal hemangiomas were analyzed.
      MATERIAL AND METHODS: Seventeen circumscribed choroidal hemangiomas associated
      with serous retinal detachment were analyzed. All patients were symptomatic but
      one. Duration of visual symptoms varied from 2 weeks to 3 years. Mean tumor
      thickness was 3,3mm (1 to 6,5mm). Mean tumor diameter was 6,5mm (2.5 to 15mm).
      Tumors were juxtapapillary in 9 cases (57%). The mean distance from the fovea was
      1,5mm (0 to 3mm), and the fovea was pathological in all cases but two. The
      tumoral surface was covered by Argon laser spots with the central avascular area
      spared in the case of subfoveal hemangioma. In the case of subretinal fluid
      persistence 3 months later, 1 or more photocoagulation sessions were carried out.
      Follow-up was 27 months (6 to 156 months). RESULTS: Success (complete subretinal
      fluid resolution) was obtained in 82.4% with 1 or 2 laser photocoagulation
      sessions. Recurrence was observed in 4 cases (23.5%) but treated with success.
      Final visual acuity, related to the initial foveal condition, was >=0.5 in 23.5%
      of cases, and >=0.1 in 70.6% of cases. DISCUSSION: Anatomical and functional
      results were satisfactory considering initial foveal conditions. Irradiation
      (external beam irradiation, proton beam therapy, brachytherapy) has been used
      with success for several years. However, radiation-induced damage was described
      in addition to a few practical disadvantages. CONCLUSION: Argon laser
      photocoagulation was an effective noninvasive therapy for circumscribed choroidal
      hemangioma. It remains for us the reference method for treating this tumor.

PMID- 11965119
TI  - [Purtscher-like retinopathy in systemic lupus erythematosus. Two cases].
AB  - Purtscher-like retinopathy is a retinopathy with vascular manifestations
      resembling Purtscher's retinopathy associated with autoimmune disorders such as
      lupus erythematosus. We report two cases of blurred vision associated with
      multiple whitish patches scattered over the macular and peripapillary areas. In
      the absence of trauma, these symptoms led us to systemic lupus erythematosus. The
      diagnosis was confirmed by the immunological and biological examinations. A
      steroid treatment was given with poor visual response. Purtscher-like retinopathy
      is a rare complication of systemic lupus erythematosus and there is some
      controversy about its pathogenesis and its treatment.

PMID- 11965120
TI  - [Bilateral exophthalmos diabetes insipidus: Erdheim-Chester disease. Clinical and
      radiological findings].
AB  - The authors report a case of a 61-year-old man presenting bilateral exophthalmos
      and diabetes insipidus. A retro-orbital biopsy revealed nonspecific
      fibrocollagenic infiltration. The diagnosis of Erdheim-Chester disease was evoked
      when a multivisceral affection (retroperitoneal and mediastinal periaortic
      fibrosis) with specific bone localization became evident. The histopatholgical
      study of a bone biopsy showed xanthogranulomatous infiltration. The patient died
      a few months later of an intercurrent infection.

PMID- 11965121
TI  - [Ophthalmic manifestations of acute leukemia].
AB  - Orbital and ocular lesions are the third most frequent extramedullar locations of
      acute leukemia after the meninges and testicles. These lesions are treated as a
      central nervous system lesion; therefore diagnosis is essential to therapeutic
      adjustment. We present a retrospective study on charts of children treated for
      acute leukemia between 1996 and 1998. Ophthalmic examination was carried out when
      there were ocular symptoms. One hundred ninety-six children were treated for
      acute leukemia. Twelve children (6.1%) had an ocular and orbital lesion: 7 boys
      and 5 girls, with an average age of 6 years. Six had acute lymphoblastic
      leukemia, 6 had acute myeloid leukemia. Visual acuity was 1/10 in 9 children.
      Four children had an initial orbital lesion with a rapidly progressing
      exophthalmos. The hemogram and myelogram showed a granulocytic sarcoma. Two
      children who had been previously treated for acute leukemia presented a bilateral
      anterior uveitis with hypopyon; anterior chamber paracentesis showed blast cells
      and confirmed the ocular relapse. A corneal lesion was found in 2 children and in
      2 cases, the optic nerve had edema; a decrease in visual acuity was the sign of
      the optic nerve lesion. Two patients had retinal infiltration with hemorrhages in
      the posterior pole. Prophylaxis consists of intrathecal injection of methotrexate
      and reinforcement of chemotherapy. Central nervous system irradiation is seldom
      used in children. Orbital and ocular lesions carry a poor prognosis according to
      the majority of authors. Two years after diagnosis of the ocular lesions, only 1
      of the children studied remains alive.

PMID- 11965122
TI  - [Macular coloboma type Leber's congenital amaurosis].
AB  - Three brothers, with the macular coloboma type Leber's congenital amaurosis aged
      10, 8, and 6 years respectively, are described in this report. Only the two elder
      brothers were symptomatic while the third patient had no complaint at the time of
      diagnosis. The patients had no associated systemic or ocular disorders, including
      nystagmus. They had mild myopic astigmatism. All three had a relatively well
      circumscribed bilateral macular atrophy with a seemingly normal peripheral
      retina. The electroretinogram was non recordable but the visualy evoked potential
      responses were within normal limits. During three years of follow-up, the macular
      lesions did not progress and the visual acuity did not deteriorate further. Our
      experience with these three familial cases supports the general view that the
      macular coloboma variant does not necessarily have the typical signs and symptoms
      and perhaps also the dismal prognosis of classic Leber's congenital amaurosis,
      and as such should stand as a distinct subtype of the disease.

PMID- 11965123
TI  - [Contact lens wearers as candidates for LASIK surgery: two pitfalls to avoid].
AB  - We present two cases of persons wearing hard contact lenses resulting in corneal
      modifications which could have falsified the indications for LASIK. CLINICAL
      CASES: In the first case the use of hard contact lenses led to thickening of the
      cornea which might have led to an erroneous indication for LASIK and an excessive
      thinning of the cornea. In the second case, the shape of the cornea was modified
      and the rigid lens masked a subclinical keratoconus. CONCLUSION: Since corneal
      ectasia is the major complication of LASIK surgery due to excessive thinning of
      the cornea or LASIK surgery on an undiagnosed keratoconus, these two cases
      illustrate the importance of a pre-LASIK eye examination for patients wearing
      hard lenses several weeks after these contact lenses have been discontinued.

PMID- 11965124
TI  - [Intraocular cysticercosis: a difficult diagnosis].
AB  - The authors describe a case of intraocular cysticercosis discovered in the
      ophthalmology department ef Edouard Herriot Hospital. With no biological signs,
      the diagnosis was made after vitrectomy because the visit was late in the course
      of the disorder, the patient lived in the mountains, and he had failed to mention
      a trip to the West Indies 3 months before. The symptomatology began with uveitis
      worsened in 10 days by greater inflammation in spite of successive
      corticosteroids, antibiotic, and antiviral therapy. Repeated examination and
      serological and radiological investigations did not help establish the etiology.
      Only vitrectomy provided the diagnosis, the vitreous containing cysticercus. This
      discover was all the more surprising that the patient lived in the French Alps
      and a trip 3 months before had been forgotten. A review ol the literature allowed
      us to rapidly start a postoperative parasite examination to check for cerebral,
      muscular, cardiac, and subcutaneous localizations and to start treatment with
      praziquantel (50 mg/kg per day) with corticotherapy (1 mg/kg per day). The eye
      evolved toward a very inflammatory phthisis, which led to evisceration.

PMID- 11965125
TI  - [A review of mathematical descriptors of corneal asphericity].
AB  - PURPOSE: Corneal asphericity may be modeled on a conic section which can be
      described by the apical radius of curvature in the meridian studied and by a
      measure of the degree of asphericity. MATERIAL AND METHODS: Through an extensive
      review of the literature, we expose the principles, the population variations and
      report the application of such corneal modeling. RESULTS: The aspheric anterior
      corneal surface can be described by a conic section, defined by its radius of
      curvature and by a parameter measuring asphericity. We analyse the various
      parameters used in the literature to determine their usefulness. Conic sections,
      obtained by cutting a cone by a plane, include ellipses, hyperbolas and
      parabolas. Two useful parameters are the apical radius of the ellipse and its
      eccentricity defined in Cartesian terms by a second order equation where the
      apical radius is R and the eccentricity is e: The apical radius is that of the
      circle tangent to the apex of the conic section and e describes the variation of
      this curve with distance from the corneal apex. Baker introduced the form factor
      p making the equation: with It is easier to understand the effect of alteration
      of p than of e on corneal curvature: There is a relation between the horizontal,
      a, and the vertical, b, hemi-axes and R The advantage of this notation is that
      e(2) can be greater than 1 When p=0 the conic section is a parabola, when p<0 it
      is a hyperbola. Kiely et al. studied corneal asphericity by photokeratoscopy and
      introduced the parameter Q, where Q=p-1. Q, the asphericity factor, is used by
      the Eyesis and Orbscan systems; when Q=0 the cornea is spherical. Thus different
      parameters describe variations in corneal curvature along any meridian. Average
      anterior corneal asphericity using various keratometric systems is p=0.8, making
      the corneal section a prolate ellipse. However there is great individual
      variation, 20% of normals exhibiting oblate (p>1), paraboloid (p=0) or hyperbolic
      (p<0) corneas. all becoming more spherical with age. Little connection between
      asphericity and ametropia is reported, except for a tendency to flattening in
      myopia and towards oblateness in progressive myopia. Direct measurement of
      denuded cadaver corneas gave a prolate elliptical profile although calculation
      after deduction of epithelial thickness measured by ultrasonic biomicroscopy
      suggested p=-0.22, a hyperbolic profile. The few reports on the posterior surface
      suggest it to be hyperbolic or prolate. Increasing distance from the corneal apex
      worsens the comparison to a conic section as flattening increases. Precision can
      be improved by adding polynomial coefficients above the second degree to the
      equation of the section: The non-toric 3D corneal surface can be described by the
      following equation for the revolution of a conic section about the optic axis:
      x(2)+y(2)+pz(2)-2rz=0 where z is the axis of revolution. Since the mean value of
      p is 0.8 this corresponds to a sphere stretched along one axis, as is a rugby
      ball. Each meridian has the same radius of curvature and the value of p is
      constant. For a toric cornea the radius and value of p must be defined for two
      meridia at right angles. This corresponds to an elongation on an axis different
      from that of revolution. Similarly a toric ellipsoid is generated by rotation of
      an arc around an axis at right angles to its elongation. Because of its
      asphericity, representation of the corneal surface depends on the direction in
      which its curvature is measured: In the ellipsoidal model this depends on the
      principal meridians, the tangential, in the plane of the axis of symmetry and the
      saggittal, perpendicular to this. These may define two radii of curvature, the
      saggital (axial) and the tangential. Most algorithms assume these properties of
      ellipsoids. Asphericity is translated into variations in radius of curvature from
      apex to periphery, increasing for a flat periphery, decreasing for a steep one.
      Associated to toricity, it gives rise to the common butterfly pattern. Spherical
      aberration is minimal through a small pupil but becomes significant the larger
      the aperture, with deterioration of image quality. Raytracing allows analysis of
      the effects of non-axial rays. The mean value of Q, at -0.26 thanks to the
      naturally prolate asphericity of the cornea reduces spherical aberration by half.
      The relaxed form of the crystalline lens further reduces it by inducing the
      opposite spherical aberation to that of the cornea. This is important in
      accommodation and presbyopia. The use of an aspheric corneal surface in the
      schematic eye allows calculation of the ideal asphericity, which corresponds
      quite well with clinical findings. Radial keratotomy reverses the natural
      asphericity of the cornea. Photorefractive keratotomy (PRK) also changes
      asphericity, Q increasing to an oblate value. These changes might increase
      spherical aberration, explaining some postoperative deficiencies. Current excimer
      laser protocols ignore asphericity, relying on paraxial algorithms alone. New
      strategies to control asphericity in order to diminish spherical aberration may
      offer solutions. The original conic section models were made to improve the
      geometry of contact lenses. Understanding of asphericity is important in
      adaptation after refractive surgery. Modification of spherical aberration by
      contact lenses and corneal warpage induced by rigid lenses have also been
      studied. CONCLUSION: The approximation of the corneal surface by a conic section
      allows understanding of corneal asphericity and offers a quantitative
      description. This allows a more precise description of the corneal surface and of
      the genesis of certain optical aberrations of the eye.

PMID- 11965127
TI  - [Cornea graft complications].

PMID- 11965126
TI  - [Drugs and closed-angle glaucoma risk].
AB  - Closed-angle glaucomas arise among predisposed patients (narrow iridocorneal
      angle) in response to various stimuli. Most of the attacks are of iatrogenic
      origin: all the topical and systemic mydriatic drugs can provoke an angle closure
      glaucoma attack. Dangerous active ingredients with closed-angle glaucoma are
      active substances with anticholinergic activity (peripheral action, central
      action, with anticholinergic side-effects), active ingredients with
      sympathomimetic alpha activity (alpha 1, alpha and beta with indirect effects),
      and the active ingredients with parasympathomimetic activity
      (anticholinesterases). The proprietary medicine, whether or not they are included
      in the French dictionary Vidal((R)), are classified according to the
      administration route and their different indications. The closed-angle glaucoma
      risk after administration of these drugs is noted in the items'contraindications
      and precautions in the summary of the product characteristics enclosed in the
      marketing authorization.

PMID- 11965144
TI  - [Anatomy and imaging: a question of relationships].

PMID- 11965128
TI  - [Seborrheic keratosis of the eyelid in a young woman].
AB  - A 46-year-old female patient had a tumor of the free margin area of the superior
      right eyelid, appearing as the fourth recurrence of a primary lesion, occurring
      24 years before. The lesion was covered with a thick layer of keratin, giving it
      a grayish and black color. Excision was performed without involving the free
      margin. Histopathology disclosed that the tumor was a seborrheic keratosis, which
      was not completely removed. As the lesion was benign, no further surgery was
      performed but regular examination was recommended to the patient.

PMID- 11965145
TI  - [Pneumobilia and MRCP: value of sagittal view].
AB  - Pneumobilia can lead to artifacts at MRCP obtained from thick coronal and coronal
      oblique slabs. Axial and sagittal images can both show gas bubbles in bile ducts
      but sagittal images depict more easily the presence of an air-fluid level.

PMID- 11965147
TI  - [MR imaging of anatomical variants of ligaments, muscles and tendons at the
      ankle].
AB  - PURPOSE: To illustrate the MR imaging features of anatomical variants of
      ligaments, muscles and tendons at the ankle. MATERIAL AND METHODS. The MRI
      features of the typical anatomy of the ankle is first reviewed in order to better
      understand the appearance of anatomical variants. The features of those
      anatomical variants are reported based on data from the literature and from a
      retrospective study of 63 ankle MRI and/or MR-arthrography performed for chronic
      instability. RESULTS: Ankle anatomical variants can be separated into 3 groups
      For each variant, we report the frequency, the differential diagnosis and the
      potential clinical consequence that may, at times, require a specific treatment.
      CONCLUSION: Anatomical variants are important to consider because these
      structures can simulate disease and can sometimes be symptomatic.

PMID- 11965146
TI  - [Process management in a radiology department. Impact on the quality system].
AB  - The purpose of this work was the transition from a mode of management combining
      TQM (Total Quality Management) based on the European model "EFQM", and quality
      assurance based on the ISO 9001-1994 certification model, to the ISO 9001-2000
      certification model which imposes process management and integrates both
      management and quality assurance. In order to visualize the inter-relation
      between processes, a  processes-map  was made. That is to say a representation of
      the organization in terms of inputs and outputs. Those processes were divided
      step by step, from general to final processes which were translated into an
      algorithmic approach. Subsequently, two external auditors were asked to evaluate
      the new quality system. They used three quality standards (IOS 9001-2000, MFQ and
      ANAES) in order to determine the adaptation score of the quality system. Finally,
      the implementation of the department documentation system on an intranet was
      evaluated by means of two questionnaires: a qualitative one, dealing with staff
      acceptability, and a quantitative one, dealing with research effectiveness.

PMID- 11965148
TI  - [Local staging of prostate carcinoma with phased array MR imaging: prospective
      study over 5 years].
AB  - PURPOSE: To assess by MRI, using a pelvic phased array coil, the accuracy for
      staging prostate carcinoma and to correlate the results with the rate of positive
      surgical margins. MATERIALS AND METHODS: Between January 1995 and December 1999,
      176 patients with localized prostate carcinoma underwent a preoperative MRI
      examination using a pelvic phased-array coil (1 Tesla). MRI and histological
      results were compared in a prospective study. RESULTS: 131 were classified T2 and
      45 were classified T3 at MRI. Pathologic findings showed 103 pT2 and 73 pT3. The
      accuracy of MRI (extra capsular or vesicle extension) was 75%. The risk for a
      patient labelled T2 or T3 at MRI to have a positive surgical margin was
      respectively 13.7% and 31%. CONCLUSION: This study shows that the phased-array
      coil has a low sensitivity but a good specificity to distinguish between organ
      confined cancer or not. It shows that the risk of positive surgical margins is
      higher for T3 lesions at MRI. The low sensitivity should be improved by using a
      multi coil phased array.

PMID- 11965149
TI  - [Hydatid disease of the urinary bladder: a case report].
AB  - All organs in the human body may be affected by hydatid disease. Urinary tract
      involvement in hydatid disease is not common, corresponding to only 2-4% of
      cases. The kidneys are the most commonly affected organs in the urinary tract. We
      report a case of hydatid cyst of the urinary bladder.

PMID- 11965150
TI  - [Gas in hepatic veins associated with tunneled femoral hemodialysis catheter].
AB  - We report the case of a female patient admitted for acute renal failure who
      required hemodialysis treatment using a tunneled femoral catheter. Abdominal
      ultrasound showed isolated gas in the hepatic veins. It was related to
      manipulation of the catheter, which allowed the passage of gas bubbles from the
      inferior vena cava into the hepatic veins.

PMID- 11965151
TI  - [Esophageal mucocele: report of 2 pediatric cases].
AB  - Two cases of esophageal mucocele in pediatric patients are reported: two children
      of 5 and 9 years respectively underwent surgical isolation of the esophagus and
      esophagocoloplasty for caustic stenosis related to accidental ingestion of
      caustic soda. Clinical pattern of mediastinal compression was proved with
      cervical fistulous tract in one case. In both cases, thoracic computed tomography
      was a sensitive imaging method to demonstrate the mucocele and its extension.
      Esophageal mucocele is rarely described in children, especially following
      esophageal corrosive stricture.

PMID- 11965152
TI  - [Primary lymphoma of bone: imaging features].
AB  - Primary lymphoma of bone (PLB) has benefited from recent advances in medical
      imaging and immunohistochemical study that are of prognostic and therapeutic
      value. From 3 case reports of PLB involving the iliac bone and the skull base, we
      review the definition of PLB and their main features. The importance of complete
      initial workup for staging in order to exclude secondary bone lymphomas, more
      frequent and of worse prognosis, is emphasized. Diagnosis of PLB involving the
      skull base is more difficult to obtain and nearly always requires neurosurgical
      biopsy unlike PLB of peripheral bones that are more readily amenable to
      percutaneous biopsy.

PMID- 11965153
TI  - [Creation of an educational CD-ROM using a PACS].
AB  - Presentation of MIRIAM 2: We describe the materials used for the creation of and
      the content of a CD-ROM entitled '77 neuroradiological case reports'. We mention
      the gathering of clinical and imaging data, exclusively provided by a PACS. Our
      work demonstrates that a CD-ROM is an appropriate interactive medium for
      radiological teaching. Its creation can be simplified thanks to a PACS, but it
      nonetheless remains work intensive.

PMID- 11965154
TI  - [Cervical aortic arch presenting with right recurrent palsy in an adult].

PMID- 11965155
TI  - [Images - pain - suffering].

PMID- 11965156
TI  - [Bone and joint MRI... Not without fat!].

PMID- 11965157
TI  - [What about research in medical imaging?].

PMID- 11965158
TI  - [Imaging of complications following hip arthroplasty].
AB  - Acute complications include fractures and prosthesis dislocations. Most chronic
      complications involve mechanical or septic loosening and aggressive
      granulomatosis. Greater trochanteric pseudarthrosis, periprosthetic soft tissue
      ossifications or prosthesis conflict with the psoas muscle can also be
      responsible for groin pain. Most complications are detected with serial plain
      radiographs, but additional imaging techniques including CT scan and scintigraphy
      are sometimes necessary for pretreatment diagnosis. Pain generally indicates a
      complication but aggressive granulomatosis can be asymptomatic, thus warranting
      systematic annual plain radiographic control.

PMID- 11965159
TI  - [Imaging of patients post blunt trauma to the chest].
AB  - Blunt chest traumas are a major concern in the setting of high-speed deceleration
      accidents, since they are associated with a high mortality rate. However, their
      prompt diagnosis and treatment allows for significant improvement of blunt chest
      trauma patient's clinical prognosis. If chest radiograph remains the initial
      screening test, the role of CT is increasing since it provides fast, sensitive,
      accurate and exhaustive survey of blunt chest trauma patients. The purpose of
      this article is to review the various radiological and CT patterns of blunt chest
      lesions.

PMID- 11965160
TI  - [Efficacy of C1-C2 block with posterior parasagittal approach in the treatment of
      Arnold neuralgia in 24 patients].
AB  - The purpose of the study is to evaluate the efficacy of C1-C2 block from a
      posterior parasagittal approach to treat Arnold neuralgia. MATERIALS AND METHODS:
      24 patients have been interviewed after 33 blocks were performed. The mean delay
      was 22 months. The posterior approach had always been performed using
      fluoroscopy. 27 blocks were performed with Hydrocortancyl((R)), 6 with
      Altim((R)). RESULTS: 71% of patients were symptomatically improved after one
      month, 62% after 3 months and more than 50% after one year. Using a visual
      analogue scale, pain was reduced of 5.8, i.e. 70% of patients were improved. An
      important reduction of pain killer requirements was noted for improved patients,
      patients with pain recurrence asked for a new infiltration. No significant side
      effect was noted. CONCLUSION: Our method seems to be an efficient alternative to
      blocks performed on the origin of the nerve and to surgical treatment.

PMID- 11965161
TI  - [Prevalence and morphology of pineal cysts discovered at pituitary MRI: review of
      1844 examinations].
AB  - PURPOSE: To evaluate the frequency, morphology and clinical long term evolution
      of pineal cysts depicted on MRI. PATIENTS AND METHODS: one thousand eight hundred
      and forty four (1 532 women and 126 men) MRI examinations were retrospectively
      reviewed. Coronal and sagittal spin echo T1 weighted sequences without and with
      gadolinium injection were performed, completed with spin echo T2 weighted images
      when a cystic sellar lesion was suspected. A pineal cyst was diagnosed as a
      rounded well defined lesion, with fluid signal in an enlarged pineal gland.
      Follow-up examinations were performed to evaluate the efficacy of the treatment
      of the sellar lesion. RESULTS: Twenty one epiphyseal cysts (1.27%) were diagnosed
      in 20 women (1.31%) and one man (0.79%). Their size was 1,2 +/- 0,4 cm (0,3 to 2
      cm). They were asymptomatic. In 10 patients, follow-up MRI examinations did not
      show any change in size. During the clinical follow-up, these twenty-one patients
      remained asymptomatic (6 months to 5 years). CONCLUSION: The incidental detection
      of a pineal cyst at MRI is not exceptional. This lesion's pattern appears
      characteristic and their reputation of benignity is confirmed in our study.

PMID- 11965162
TI  - [MR imaging findings of bone marrow reconversion induced by growth factors in 3
      patients].
AB  - MRI is now the method of choice for bone marrow imaging. The MR appearance of
      bone marrow is influenced by the relative amounts of its fatty or hematopoietic
      components. In the following study, we report different patterns in changes
      consistent with reconversion into hematopoietic tissue of fatty marrow that were
      observed in 3 patients who received hematopoietic growth factors in combination
      with their chemotherapy for musculo-skeletal tumors of lower limbs.

PMID- 11965163
TI  - [Value of imaging in GAPO syndrome].
AB  - GAPO syndrome is a rare genetic disorder. The term GAPO is the acronym for the
      manifestations: Growth retardation, Alopecia, Pseudoanodontia and Optic atrophy.
      We report the case of a 12 year-old boy with GAPO syndrome. Physical examination
      was remarkable for: dilated scalp veins with two flaccid masses of the vertex and
      the right mastoid area that was pulsatile with an audible bruit. Brain magnetic
      resonance imaging (MRI), magnetic resonance angiography (MRA) and cerebral
      angiography showed very prominent cortical veins, hypoplasia of the left
      transverse sinus, agenesis of the left jugular vein and left sigmoid sinus with 2
      enlarged emissary veins underlying the palpable scalp masses. We suggest that
      brain MRI and MRA should be performed in patients with GAPO syndrome to detect
      anomalies of the intracranial venous circulation.

PMID- 11965164
TI  - [French Guyana's case of renal pseudotumor caused by actinomycosis].
AB  - We report one case of renal pseudotumor caused by actinomycosis with cutaneous
      fistula in a young French Guyana's boy. Diagnosis before surgery and histology is
      difficult. CT is the best examination to evaluate the extent of the disease. A
      short review of the literature is presented.

PMID- 11965165
TI  - [Cricoid chondronecrosis after prolonged endotracheal intubation].
AB  - Subglottic area injuries after prolonged endotracheal intubation are relatively
      frequent but cricoid cartilage necrosis is rare, with uncertain prognosis.
      Endoscopic findings are evocative even when clinical signs are not. When
      suspected, CT scan is required. The CT appearance is not specific, but the
      diagnosis can be strongly suggested in cases of fragmentation and collapse of the
      cricoid cartilage. We report two cases of cricoid chondronecrosis.

PMID- 11965166
TI  - [Rhino-orbito-cerebral mucormycosis].
AB  - Rhino-orbito-cerebral mucormycosis is a rare fungal infection, invading rapidly
      the nasal cavity, paranasal sinuses, orbits and intracranial structures. It most
      often occurs in predisposing conditions (diabetics, immunosuppressed patients).
      The authors report the case of a diabetic patient who presented with extensive
      necrotic lesions of the face in spite of appropriate antistaphylococcic therapy.
      Diagnosis was confirmed by histologic and mycologic tests. The outcome was
      favorable after Amphotericin B therapy, daily debridement, and optimal control of
      the diabetes.

PMID- 11965167
TI  - [Quid? Lead pellets in the appendix].

PMID- 11965170
TI  - [Rapid-eye-movement sleep disorders in Parkinson's disease].
AB  - During the past 10 years, there has been an increasing interest in the study of
      rapid-eye-movement (REM) sleep in neurodegenerative diseases and more particulary
      in Parkinson's disease (PD). This interest is justified by the strong association
      observed between these diseases and REM sleep behavior disorder (RBD). In the
      first section of this paper, a critical review of the literature on the presence
      of REM sleep disorders in PD is presented. Studies that show an association
      between PD and RBD are reviewed. Studies that report the presence of other REM
      sleep disorders in PD (short latency, abnormal length and/or proportion of REM
      sleep, increasing occurrence of hallucinations) are then discussed. Limitations
      of the criteria proposed by Rechtschaffen et Kales (1968) for the quantification
      of REM sleep are also presented. Some authors believe that dopaminergic (DA)
      agents used in the treatment of PD (levodopa, bromocriptine, pergolide,
      pramipexole and selegiline) could be a responsable factor for the occurence of
      REM sleep disorders observed in this disease. The literature concerning the
      impact of these DA agents on human REM sleep is therefore critically reviewed. It
      is concluded that DA agents cannot explain on their own the presence of REM sleep
      disorders in PD. Other causes, among which the disturbance of some neurochemical
      systems linked to the neuropathological process of the disease, must be
      considered in order to explain these REM sleep disorders. In the second section
      of this paper, we present the different pathophysiological hypotheses proposed to
      explain REM sleep disorders in PD, such as a dysfunction of the cholinergic,
      noradrenergic, serotonergic, dopaminergic or GABAergic neurons. Emphasis is
      placed on the role of cholinergic neurons of the pedunculopontine and
      laterodorsal tegmental nuclei, structures shown to be particularly impaired in
      PD. Neurophysiological, neuroanatomical and neuropharmacological studies
      demonstrate that these neurons are strongly implicated in the different REM sleep
      parameters (muscular atonia, electroencephalographic desynchronisation, ponto
      geniculo-occipital spikes). Finally, future research directions are proposed.

PMID- 11965172
TI  - [BREV: a rapid clinical scale for cognitive function evaluation in preschool and
      school-age children].
AB  - BREV, standing for the French "Batterie Rapide d'Evaluation des Fonctions
      Cognitive", is a rapid test to screen children with disorders of higher functions
      and to define the patterns of these disorders. We describe here two phases of the
      validation procedure. The first phase consisted in measuring the internal
      validity of the scale by testing 500 normal school children free of disability.
      The validation process provided appropriate values for each of the 18 subtests
      assessing cognitive functions (oral language, non-verbal abilities, attention and
      memory, education and memory, educational achievment) in ten age groups from 4 to
      8 years. All subtests with the same content for any revealed values which
      increased significantly with age. Inter-reliability was tested by retesting 70
      children. The second phase of validation, comparing BREV results and those from a
      large classical neuropsychological battery, tested specificity and sensitivity.
      Each of the BREV subtests were correlated with the similar subtest of the
      classical battery. Correlations between verbal and non-verbal scores and verbal
      and performance intellectual quotient (Weschler scale) were very significant.
      Sensitivity and specificity of BREV were above 75p.100;. This confirms the
      reliability of this battery for children, with good sensitivity and specificity.
      BREV is a reliable test, with carefully established norms, appropriate for
      preschool and school-age children.

PMID- 11965171
TI  - [Argyrophilic grain disease (AgD), a frequent and largely underestimated cause of
      dementia in old patients].
AB  - Argyrophilic grain disease (AgD) is a late-onset dementia morphologically
      characterized by abundant neuropil grains (ArGs). ArGs are mainly found in the
      CA1 subfield of the cornu ammonis, entorhinal and transentorhinal cortices, the
      amygdala and the hypothalamic lateral tuberal nuclei. We have recently shown that
      abnormally phosphosphorylated tau protein is the main protein constituent of ArGs
      and that tau is hyperphosphorylated in up to 80p.100 of nerve cels in areas rich
      in ArGs. We could demonstrate that at least a subset of grains are formed within
      dendrites and dendritic side-branches of neurons containing hyperphosphylated
      tau. Morphology of dendrites containing grains suggests that a process of
      progressive dendritic shrinkage is taking place in neurons bearing ArGs.
      Furthermore it became apparent that the presence of ArGs is not necessarily
      associated with a cognitive decline. Our studies on AgD cases with and without
      dementia suggest that AgD is a progressive neurodegenerative disorder with early
      subclinical lesions in anterior part of the hippocampal formation. At later
      stages involvement of more caudal parts of the hippocampal formation generally
      results in a cognitive decline. Thus, one possible explanation for the dementia
      observed in some subjects with AgD is that there is a more widepread loss of
      postsynaptic structures, including synaptic contacts, throughout the hippocampus
      entorhinal/parahippocampal complex and the amygdaloid nuclei. Most of the
      reported AgD cases are associated with neurofibrillary lesions (e.g.
      neurofibrillary tangles) which are also typical of Alzheimer's disease (AD).
      However, neurofibrillary changes do not exceed early (entorhinal and limbic)
      Braak stages which generally are not associated with a cognitive decline.
      Additional neuropathological features of AgD include oligodendroglial tau
      filamentous inclusions ( coiled bodies ), ballooned neurons and astrocytic tau
      pathology. The clinical features of AgD are poorly understood. However,
      preliminary data from retrospective studies suggest that in AgD behavioural
      disturbances will precede memory failure and memory decline. Furthermore, it has
      been shown that the ApoEe4 allele does not constitute a risk factor for the
      development of AgD. In conclusion it seems very likely that AgD is a distinct
      dementing disorder of old age that has to be distinguished from other
      tauopathies, e.g. AD, by both morphological and genetic criteria.

PMID- 11965173
TI  - [Vacuolar leucoencephalopathy induced by heroin: 4 cases].
AB  - We report 4 cases of toxic leucoencephalopathy after heroin inhalation. The
      clinical features, which usually occur some days or even longer after the last
      heroin consumption, are dominated by a cerebellar syndrome. The cerebellar
      hemispheres are almost always affected; the cerebral hemispheres, the cerebellar
      peduncles and the pyramidal tract may be affected. Vacuolar demyelination is the
      morphological substract of the lesions, which are symmmetrical, not contrast
      enhancing, hypodense on CT scan and hyperintense on T2-weighted MRI. The
      pathophysiology is unknown and seems different from post-anoxic
      leucoencephalopathy. The disease is usually progressive leading sometimes to
      death, but some cases show slow recovery.

PMID- 11965174
TI  - [Subjective blockage in Parkinson's disease].
AB  - Akinetic symptoms or off-period motor signs in patients with Parkinson's disease
      and motor fluctuations can be associated with subjective symptoms. A systematic
      interview was conducted in a series of 24 patients. Sixteen out of 24 (67 p.
      cent) experienced these subjective symptoms as on-off non motor symptoms that
      were classified in three groups: energy lost consistent with a severe asthenia,
      perceptive and cognitive alterations, and emotional troubles such as panic and
      depression. These phenomenons could be combined in some patients and were
      sometimes asynchron to akinesia. In some patients (six cases reported), they
      occurred without any akinesia but could totally inhibit patients daily
      activities, and so could be described as subjective off-period . Frequently, the
      patients did not distinguish them from motor disability. Their persistence, after
      subthalamic nucleus stimulation or intrastriatal transplant, could interfere with
      functional results, even though akinetic symptoms had disappeared. CONCLUSION:
      subjective phenomenons during off-periods are frequent. Their frequency is
      underestimated due to a non-targeted examination. Subjective off-periods are
      symptoms of Parkinson's disease, partly independent from off motor symptoms, and
      important to consider in evaluation of therapeutics, especially surgery.

PMID- 11965175
TI  - [Familial indifference to pain with somatosensory asymmetry: possible central
      anomaly].
AB  - A family of seven siblings is described. The mother and six siblings have been
      examined, the eldest and youngest of whom suffer from  congenital indifference to
      pain , although both were ticklish, and itched. The functions examined included
      somatosensory perception thresholds and autonomic functions; perception
      thresholds were greatly raised in the painfree subjects and to a lesser extent in
      some other family members, asymmetrically in all cases, being higher in the
      dominant hand. Painfree Subject 1 also underwent cerebrospinal fluid analysis at
      age 16, which showed normal B-endorphin levels but undetectable enkephalins.
      Electrophysiological tests when a child demonstrated notably that most (raised)
      measured values were lowered by naloxone. Light microscopic sural nerve biopsy
      performed on painfree Subject 1 in childhood did not suggest any abnormalities
      other than a thickened nerve sheath. Threshold asymmetry has not been observed in
      large numbers of subjects without neurological deficits. There were no
      significant autonomic changes in any tested family member, though there was some
      asymmetry. It is suggested that the findings may imply a congenital anomaly of
      the central nervous system which accounts for the somatosensory, biochemical, and
      electrophysiological abnormalities.

PMID- 11965176
TI  - [Hallucinations, delusions, and nocturnal events in 152 Parkinson's patients: a
      regional survey].
AB  - Parkinson's disease cannot be reduced to its motor symptoms. Psychological and
      behavioral disorders often accompany its development. Our study was conducted in
      June 1999 among 36 neurologists practicing in hospital or private clinic settings
      in the Poitou-Charentes area. Neurologists were requested to record
      hallucinations, delusions and nocturnal events observed in Parkinson's patients.
      A total of 152 reports were collected from 17 physicians. Fifty-three percent of
      the patients attended hospital clinics and 47p.100; were seen at the physician's
      office. Hallucinations were recorded in 23.1p.100; of the patients. The risk of
      hallucination symptoms was higher among patients seen at hospital clinics and who
      had more advanced disease. Only 7.2p.100; of the patients reported delusions,
      most often of a persecution type. Nocturnal events affected 49.3p.100; of the
      patients. The appearance of such symptoms was highly related to Hoehn and Yahr
      stage and was more frequent in hospital patients. Hallucinations, delusions, and
      nocturnal events affect patients with advanced Parkinson's disease, associated
      with long-term L-dopa treatment. Eighty-three percent of the patients had such
      symptoms and most of them used L-dopa. This long-term treatment is linked to
      these three symptoms. Hallucinations were increasingly reported for patients with
      increasing long-term medication with dopaminergic agonists. Nocturnal events, for
      patients on L-dopa, were associated with advanced disease, long-term treatment
      with L-dopa, and hospitalization. Psychic and behavioral disorders appear
      frequently in Parkinson's disease patients and are inter-related. Physicians
      should be aware of the relationship with treatment to avoid aggravation.

PMID- 11965177
TI  - [Acute rhombencephalitis with fever and bilateral hearing loss secondary to
      Gougerot-Sjogren's syndrome].
AB  - The usual polymorphic central nervous system involvement observed in primary
      Sjogren's syndrome is classified as monofocal, multifocal or diffuse involvement.
      We present a case of acute rhombencephalitis associated with hearing loss that
      could correspond to an intermediate form between diffuse and monofocal
      involvement. The acute onset with fever and not clinical sign of xerostomia or
      xerophthalmia suggest the possibility of vascular-like or infectious-like forms.
      We emphasize the importance of obtaining a minor salivary gland biopsy for
      diagnosis of Sjogren's syndrome and suggest that Sjogren's syndrome could be
      frequently misdiagnosed.

PMID- 11965178
TI  - [A patient with white matter involvement and superficial hemosiderosis of the
      central nervous system].
AB  - We present a patient with a superficial siderosis and a white matter involvement
      on MRI and a demyelinating pattern on visual evoked potentials. White matter
      involvement is supposed to be secondary to vascular modifications induced by
      superficial siderosis.

PMID- 11965179
TI  - [Acute orthostatic intracranial hypotension].
AB  - The case of a young female with an acute idiopathic low cerebrospinal fluid
      pressure is presented. Clinical-imaging manifestations were typical and two
      consecutive blood patches resulted in a complete and durable resolution of the
      symptomatology. We present a review of the various investigation and therapeutic
      techniques.

PMID- 11965180
TI  - [Anterior choroidal artery infarction revealing polyarteritis nodosa].
AB  - An 81-year old man presented with a sudden right ataxic hemiparesis. Brain CT
      scan showed a left anterior choroidal artery territory infarction. Biological
      signs of inflammation were present without any evidence of infection or neoplasm.
      The patient's clinical status deteriorated with fever, loss of weight and
      confusion. Muscle biopsy showed characteristic abnormalities of polyarteritis
      nodosa (PAN). Oral corticosteroids plus monthly pulse intravenous
      cyclophosphamide were started. A rapid clinical improvement was observed as well
      as the resolution of inflammation within one month. Twenty months later, the
      patient had recovered normal cognitive function and was able to carry out all
      usual activities. We describe the CNS complications of PAN and the therapeutic
      options.

PMID- 11965181
TI  - [Refsum's disease: evolution 35 years after diagnosis].
AB  - Refsum's disease (Heredopathia atactica polyneuritiformis) is an autosomal
      recessive disease caused by a defective alpha oxidation of a C20 fatty acid: the
      phytanic acid. Deficiency of a peroxysomal enzyme called "Phytanoyl-Co-A alpha
      hydroxylase" leads to an accumulation of phytanic acid. The clinical picture
      include retinitis pigmentosa, peripheral neuropathy, ataxia and elevated
      cerebrospinal fluid protein concentration. Firstly described in 1946 by Sigvald
      Refsum, dietary treatment leads to an improvement of neurological symptoms but
      does not affect retinal changes. To our knowledge, there is no data in the
      literature on long term follow-up. A patient with Refsum's disease diagnosed in
      1965 presented with facial paralysis. The phytanic acid concentration was low,
      CSF protein level was normal leading to diagnosis of Bell's palsy. This
      observation is of particular interest because after 35 years evolution of the
      disease, the only handicap was visual impairment, with no loss of muscle strength
      or sensory deficit.

PMID- 11965182
TI  - [MRI of a cauda equina lymphoma].

PMID- 11965183
TI  - [Seizures and vascular epilepsy: clinical, electroencephalographic and
      scanographic features].

PMID- 11965197
TI  - A current perspective on genetic testing for breast and ovarian cancer: the oral
      contraceptive decision.
AB  - A clinician faces a problem in how best to counsel the woman with a family
      history of breast or ovarian cancer about her options for pregnancy prevention.
      The physician must guide her as she makes new and complex decisions. Recent data
      strongly support an amplified effect of the estrogens in oral contraceptives for
      the woman with a genetic risk for breast cancer. Nonetheless, a woman's immediate
      need to prevent pregnancy may be much more important to her than worrying about
      the long-term risk of breast cancer. Another factor is that oral contraceptives
      prevent ovarian cancer, so the physician may wish to prescribe them to protect
      her from ovarian cancer. In some genetic backgrounds, however, oral
      contraceptives not only do not prevent ovarian cancer, but they may raise the
      risk of breast cancer so significantly that they should not be taken. With other
      genetic backgrounds, oral contraceptives will protect the woman from ovarian
      cancer without much effect on her breast cancer risk. When does each of these
      cancer risks or benefits become significant? The clinician can provide an
      important benefit to a woman who must prevent pregnancy yet worries about her
      cancer risk. The physician can help her evaluate the evidence, with its gaps and
      uncertainties, in the context of her own preferences. To assist in this
      evaluation, this decision aid provides base-line estimates of the cancer risk
      that accompanies each of a woman's options. In some cases, genetic testing is
      likely to provide valuable information as she makes choices about contraception
      and the risks vs. benefits of different alternatives available to her.

PMID- 11965198
TI  - Does former use of hormonal contraception predispose women to accept hormone
      replacement therapy?

PMID- 11965199
TI  - Editorial peer review.

PMID- 11965200
TI  - Peer review is essential for both print and electronic publications.

PMID- 11965201
TI  - Gastrointestinal medications and procedures in osteoarthritis patients treated
      with rofecoxib compared with nonselective NSAIDs.
AB  - CONTEXT: Patients treated with nonselective cyclooxygenase inhibitors
      (nonsteroidal anti-inflammatory drugs [NSAIDs]) often experience dyspepsia and
      upper gastrointestinal (GI) adverse effects, and frequently require GI
      comedications and diagnostic procedures. OBJECTIVE: This study combined existing
      data to test the hypothesis that GI comedications and GI diagnostic procedures
      occur less frequently in osteoarthritis (OA) patients treated with rofecoxib
      compared with nonselective NSAIDs. DESIGN: Combined analysis of 8 randomized
      controlled clinical trials. SETTING: Rheumatology and general practice clinics.
      PATIENTS: Men and women aged 40 years and older with OA. INTERVENTIONS: Random
      assignment to placebo (n = 514), rofecoxib (n = 3357; 12.5, 25, or 50 mg daily
      combined; average 24.7 mg), or NSAIDs (n = 1564; ibuprofen 800 mg thrice daily,
      diclofenac 50 mg thrice daily, or nabumetone 1500 mg daily, combined). MAIN
      OUTCOME MEASURES: The cumulative incidence of patients using GI comedications
      (antacids, antispasmodics, antiflatulents, antiregurgitants, H2 antagonists,
      proton pump inhibitors, sucralfate, prostaglandins, other antiulcer therapy) and
      needing GI procedures (upper GI barium studies, upper or lower GI endoscopies)
      over 12 months. RESULTS: Compared with those treated with NSAIDs, patients
      treated with rofecoxib had a significantly lower incidence of GI comedication use
      (17.5% vs 27.0%, P <.001) and GI procedures (3.3% vs 5.3%, P =.02) over 12
      months. Similar results were seen in analyses of protocols with placebo; in these
      studies, rates of GI comedications and procedures were highest with NSAIDs, while
      those with rofecoxib and placebo were similar to each other. CONCLUSIONS: OA
      patients treated with rofecoxib for up to 12 months required significantly less
      GI comedication and significantly fewer GI procedures than those treated with
      NSAIDs.

PMID- 11965202
TI  - Case report--slowly enlarging mass of the dorsal right hand in a pregnant woman.

PMID- 11965203
TI  - Thrombolysis for acute myocardial infarction: drug review.
AB  - The proof of efficacy of thrombolysis for acute myocardial infarction (AMI)
      depends on 9 randomized placebo-controlled trials totaling 58,511 patients. The
      meta-analysis of these trials showed an overall survival advantage of about 2%
      (11.5% vs 9.6%) in favor of thrombolysis. Iatrogenic deaths from thrombolysis
      complications occur in about 1% of AMI patients. Timely opening of the infarct
      related artery (IRA) allowing myocardial reperfusion has been proposed to explain
      any survival advantage seen with thrombolysis ("open-artery hypothesis").
      Angiographic data does not support the open-artery hypothesis as the mechanism of
      any benefit of thrombolysis. The "early hazard" (ie, increased mortality in the
      first 12 hours after thrombolysis) also suggests that the supposed survival
      benefit is due to something other than early reperfusion. The variable use of
      aspirin in the meta-analysis trials may have confounded the results and
      conclusions. In the 4 studies of the meta-analysis in which aspirin was used
      routinely (n = 21,144), the survival benefit was not statistically significant (P
      =.14). Lack of blinding in some studies and other methodologic problems may also
      call the conclusions of the meta-analysis into question. AMI registry reports
      comparing patients with and without thrombolysis have not borne out a significant
      survival advantage with thrombolysis. The National Registry of Myocardial
      Infarction (NRMI) registry data suggest that a significant number of AMI patients
      may be inappropriately receiving thrombolytics. An independent analysis of the
      NRMI mortality data adjusted for age and other risk factors would help determine
      whether thrombolysis for AMI improves survival.

PMID- 11965204
TI  - Diet and tobacco use: analysis of data from the diabetic control and
      complications trial, a randomized study.
AB  - CONTEXT: The Diabetic Control and Complications Trial (DCCT) researchers kept
      careful records of the food consumption and tobacco using habits of type 1
      diabetic subjects. However, they did not report the relationship of tobacco using
      habits with dietary intake. OBJECTIVE: Analyze the relationship between tobacco
      smoking and intake of macro and micronutrients. DESIGN: Randomized controlled
      trial. SETTING: Referral clinics in 27 academic centers. PATIENTS: Type 1
      diabetics. INTERVENTION: Using the data sets of the DCCT, this study analyzed the
      strengths of the associations between smoking and macronutrient consumption,
      hemoglobin A1c (HbA1c), body mass index (BMI), and serum lipid levels at the
      study baseline, 2 years, and 4 years. MAIN OUTCOME MEASURES: Statistically
      significant correlations between smoking and nutrient intake, HbA1c, and serum
      lipid levels. RESULTS: Cigarette, cigar, or pipe use at each time interval
      correlated with significantly increased caloric intake in males but not in
      females. In both males and females, tobacco users consumed more fat, cholesterol,
      and alcohol. Female smokers had higher serum low-density lipoprotein (LDL)/high
      density lipoprotein (HDL) ratios and triglycerides. Serum cholesterols, LDL/HDL
      ratios, LDL cholesterols, and triglyceride determinations in male tobacco users
      significantly exceeded those in nonsmoking males. HDL cholesterols were lower in
      both female and male tobacco users. Nutrient intake of former tobacco users
      resembled that of nonusers rather than current users. CONCLUSIONS: A significant
      association exists between smoking and a diet with higher risks of
      atherosclerosis, cancer, and other degenerative diseases. The strong association
      of tobacco with heart disease, stroke, vasculopathies, and various malignancies
      may be in part due to its association with a higher fat diet. The higher fat diet
      of tobacco users probably accounts in part for their higher risk of developing
      type 2 diabetes and hyperlipidemia. Tobacco users should be informed about the
      diet and tobacco use association.

PMID- 11965205
TI  - The anthrax scare: US healthcare as usual.

PMID- 11965206
TI  - Service from the heart--lessons from Mozambique.

PMID- 11965207
TI  - Health insurance for unemployed workers.
AB  - OBJECTIVE: In this article, we seek to inform the debate over providing
      assistance to workers who lose their jobs during the recession by assessing the
      potential impact of an economic downturn on health insurance coverage and
      reviewing available approaches to secure coverage for unemployed workers and
      their families. We also summarize recent research and analysis to examine the
      likely challenges and benefits of these approaches. DATA SOURCE: Data and
      analysis are primarily based on the Census Bureau's Current Population Survey,
      the Urban Institute's National Survey of America's Families, and Medicaid data
      from the Centers for Medicare and Medicaid Services. We also draw on recent
      surveys and analysis conducted by researchers in the health policy field.
      CONCLUSIONS: Maintaining health insurance coverage for unemployed workers is
      important to helping individuals and to stimulating our economy. While some
      families may be assisted by efforts to subsidize COBRA extension coverage, the
      potential reach of such an initiative is limited. Building on public programs
      such as Medicaid offers a targeted, efficient, and effective option but also
      presents financing challenges to federal and state governments.

PMID- 11965208
TI  - Challenging the conclusions drawn in "Thrombolysis for acute myocardial
      infarction: drug review".

PMID- 11965210
TI  - Motility of minute intestinal fluke, Haplorchinae spp, metacercariae in fish
      dishes prepared by different uncooked methods.
AB  - CONTEXT: Fish-borne trematode is a worldwide problem, with the number of people
      infected by liver flukes alone estimated at 21 million. In addition to the major
      liver flukes, Opisthorchis viverrini and Clonorchis sinensis, several types of
      intestinal flukes also use cyprinoid fish as the intermediate host. Traditional
      ingestion of undercooked and uncooked fish preparations is a major factor in
      pathogen acquisition. OBJECTIVE: To examine the motility of Haplorchinae spp
      metacercariae in matched minnows using a number of preparation methods that mimic
      traditional practices. DESIGN: Several freshly killed freshwater fish,
      Cyclocheilichthys armatus, were purchased from the local market and sent to the
      authors' laboratory to be examined under a stereoscopic microscope for active
      Haplorchinae spp metacercariae. A total of 10 fish were infected with many active
      metacercariae and used in the preparation of uncooked fish dishes. Five different
      raw fish dishes that mimic traditional meals (2 fishes/dish) were prepared using
      the following methods: 1) left to dry at room temperature; 2) frozen at -20
      Celsius; 3) refrigerated at 4 Celsius; 4) marinated in saline (5% sodium chloride
      solution); and 5) marinated in 5% acetic acid solution to mimic traditional
      vinegar. The motility of the metacercariae in each of these dishes was examined
      under a stereoscopic microscope. Motility was estimated as the level of activity
      or degeneration of the metacercariae at the start of the experiment and then
      every 30 minutes until all the parasites appeared degenerate (and therefore,
      presumably not viable). RESULTS: Degeneration of the parasites was slowed by
      cooling: degeneration of all metacercariae took approximately 5 hours in the
      refrigerated or frozen fish, compared with 3 hours in all other dishes left at
      room temperature. CONCLUSION: The study substantiates the epidemiologic data
      demonstrating transmission of these types of pathogens despite freezing,
      pickling, and salting. Although the tradition of eating uncooked fish is deeply
      rooted in Thailand, constant efforts need to be made to discourage this practice.

PMID- 11965211
TI  - Management of insomnia--the role of zaleplon.
AB  - CONTEXT: Insomnia is the most frequently reported sleep symptom, severely
      affecting up to 15% of the US population. The need to effectively treat this
      disorder is underscored by the significant adverse consequences on the
      productivity, safety, overall health, and quality of life of the affected
      individual. Pharmacologic intervention has traditionally involved the use of
      benzodiazepine receptor agonists (BzRAs), for which efficacy and general safety
      have been established. OBJECTIVE: The purpose of this paper is to examine the
      potentially unique role of zaleplon in the treatment of insomnia. DATA SOURCE:
      The clinical experience of the authors was critically applied to peer-reviewed
      published papers or abstracts regarding zaleplon, which were identified via
      MEDLINE (1995-September 2000). RESULTS: Adverse effects, usually related to
      residual sedation, impose limits on the use of older BzRAs and have prompted the
      development of new sleep medications with advantageous adverse event profiles.
      Zaleplon demonstrates a very rapid onset and offset of effect that permits
      symptomatic rather than prophylactic administration, resulting in comparable
      efficacy and reduced risk of the adverse effects associated with longer half-life
      agents. CONCLUSIONS: The characteristics of zaleplon may translate into distinct
      and significant clinical advances in the treatment of insomnia.

PMID- 11965212
TI  - Obituary for John M. Eisenberg, America's top doc.

PMID- 11965213
TI  - Characteristics of women internists.
AB  - OBJECTIVE: The authors wished to describe characteristics of US women general and
      subspecialized internists and to compare them with each other and with other US
      women physicians. DESIGN/SETTING/PATIENTS: The authors used data from the Women
      Physicians' Health Study (WPHS), a national questionnaire-based study of 4501
      women physicians. RESULTS: Women internists reported less (P < or =.01) career
      satisfaction than did other women physicians. Women general internists were also
      more likely than other women primary care physicians to report severe work stress
      and were more likely than other women internists and other primary care women
      physicians to want to change their specialty if reliving their lives. Compared
      with other subspecialties, subspecialized women internists were more likely to
      report working too much, and reported lower personal incomes and more hours of
      nonclinical work than did other women internists or other women specialists. For
      virtually all 14 examined counseling practices, subspecialized women internists
      reported more interest and confidence regarding counseling (and usually by
      substantial margins), and believed that they were better trained in counseling
      than were other women subspecialists. Women general internists performed somewhat
      better regarding counseling than did other women primary care practitioners,
      although this differential was neither as consistent nor as strong as those among
      women subspecialists. CONCLUSION: US women general and subspecialized internists
      differ in a number of ways from each other and from other US women physicians.
      Particularly significantly, US women internists report several risk factors for
      career dissatisfaction, and, in fact, have less career satisfaction than do other
      women physicians.

PMID- 11965214
TI  - Chemoprevention of coronary atherosclerosis: the role of lipid interventions. A
      position paper of the American Council on Science and Health.
AB  - Atherosclerosis is not an inexorable part of aging. Addressing unhealthy
      lifestyle behaviors will go a long way toward reducing the current burden of
      atherosclerosis without widespread drug therapy. The question is whether this is
      possible, given the demand of our modern culture. It is not yet clearly
      established precisely where pharmaceutical lipid lowering or chemoprevention fits
      in the broader spectrum of prevention and treatment of atherosclerosis and its
      complications. Anatomic interventions, such as angioplasty or bypass surgery,
      targeted to obstructing but stable lesions, are likely to be only of limited
      effectiveness. On the other hand, cholesterol interventions, not only as a long
      term means of dealing with atherosclerotic sequelae but as a short-term means of
      reducing plaque activity and events, are demonstrably effective. Aggressive
      cholesterol lowering will, moreover, substantially reduce the requirement for
      angioplasty and bypass procedures. Although more difficult to prove, earlier
      intervention can almost surely lower the risk of later, potentially lethal,
      coronary events.

PMID- 11965215
TI  - Innovative approaches to cervical cancer prevention.

PMID- 11965217
TI  - An ecological approach to physical activity in African American women.
AB  - Physical activity in women has assumed increasing significance as a policy issue
      as a result of the release of the 1996 Surgeon General's Report on Physical
      Activity and Health. This report revealed that women in the United States were
      less likely than men to adhere to the recommended guidelines for physical
      activity. African American women are less likely than white women to participate
      in leisure time physical activity across age, occupational, and income groups.
      The purpose of this study was to use the Ecological Model of Health Promotion to
      explore policy, environmental, and individual factors influencing physical
      activity of middle- to older-aged African American women in a mixed income
      community in a large midwestern city. Focus group discussions were held with 3
      groups of women -- administrators/community leaders, exercisers, and
      nonexercisers. Thirty-three women between the ages of 40 and 78 participated in
      the study. The women identified 6 themes influencing physical activity:
      perceptions of physical activity and exercise; perceived barriers to exercise;
      perceived benefits of and motivators to exercise; past and present opportunities
      for exercise; factors that enhance the successful delivery of an exercise
      program; and coalition building to deliver an exercise program to women in the
      community. The results of this study reveal that to successfully increase
      physical activity in an ethnic urban community, researchers and other concerned
      individuals need to collaborate at multiple ecological levels, with an initial
      emphasis on establishing coalitions between institutions, community groups,
      policy makers, and individuals.

PMID- 11965218
TI  - Medical abortion: overview and management.
AB  - Medical abortion regimens are safe, effective, and offer a new range of choices
      for patients and providers. In September 2000, the US Food and Drug
      Administration (FDA) approved a regimen of mifepristone and misoprostol, which
      effects abortion by luteolysis, uterine contractions, and expulsion of the
      products of conception without surgical instrumentation. The regimen requires
      that a provider be capable of diagnosing ectopic gestations and be able to make
      arrangements for a surgical abortion in the case of failure or medical
      emergencies. With a medical abortion, the pregnancy is passed spontaneously, and
      there may not be tissue obtained for confirmation. Physicians must be aware of
      their state requirements with regard to expulsed tissue examination. Completion
      of the procedure can be established by ultrasound or by measurement of serum
      levels of human chorionic gonadotropin (hCG). The FDA-approved protocol allows
      for use up to 49 days after the first day of the last menstrual period (LMP) and
      consists of mifepristone 600 mg orally on day 1, misoprostol 400 mcg orally on
      day 3, and a follow-up appointment on days 12-20. Half of all patients pass their
      pregnancy in the first few hours after the second visit. It is important to be
      able to determine the difference between expected bleeding, 14 days on average,
      and the complication of hemorrhage, as 2% to 10% of patients require a surgical
      abortion. Continuing viable pregnancies are rare. Several other regimens can
      safely expand options and reduce expense, including protocols using methotrexate.
      Medication indications and contraindications, management strategies for patients
      undergoing treatment with these regimens, and safety issues are reviewed.

PMID- 11965219
TI  - Conservative management of eclampsia and severe pre-eclampsia--A Bangladesh
      experience.
AB  - OBJECTIVE: To observe whether the pregnancy can be safely continued for a
      reasonable period to gain fetal maturity in cases of eclampsia and severe pre
      eclampsia. METHODS: Fifty-one patients were followed up in a specialized care
      (eclampsia) unit in Dhaka Medical College and Hospital between January 1998 and
      October 2000. Twenty-one patients with complaints of headache and blurred vision,
      and 30 patients with history of convulsion, all at gestational age < 36 weeks,
      were enrolled for this study. Magnesium sulfate was used to prevent convulsion in
      severe pre-eclampsia and to control convulsion in eclampsia. After conducting a
      baseline assessment, pregnancy was continued to gain fetal maturity. Patients
      were monitored closely. Diastolic blood pressure, 24-hour urinary total protein
      (UTP), and serum uric acid were chosen as the main parameters to detect the
      deterioration of a patient's condition. Pregnancy was terminated when
      deterioration occurred, as determined clinically or by 1 or more of the above
      parameters. Dexamethasone was used during the waiting period for fetal lung
      maturity. Patient outcomes were analyzed. RESULTS: At admission, the patients'
      mean gestational age ( SD) was 30.65 2.38 weeks, and the range was 24-34 weeks.
      Mean diastolic blood pressure was 109.06 11.61 mm Hg, 24-hour UTP was 2.25 1.73
      g/24 h, and serum uric acid level was 5.5 1.12 mg/dL. Pregnancy was continued for
      a mean of 13.27 8.26 days (range, 3-35 days). Thirty-two babies (62.75%) with
      birth weight 1.0-2.5 kg (2.02 0.45) were born alive. Six of them (18.75%)
      weighing between 1.0 and 1.5 kg at birth were referred to the intensive care
      unit, and 1 (3.13%) weighing 1 kg at birth died within 5 minutes after birth.
      Among live-born babies, 93.75% were in good condition at the time of discharge
      from the hospital. Intrauterine death occurred in 19 (37.25%).cases. Twelve of
      them delivered spontaneously within 7 days of death and 7 required induction. In
      all cases, maternal condition was satisfactory. CONCLUSION: In carefully selected
      cases and with close supervision, pregnancy may be continued in women with
      eclampsia and severe pre-eclampsia to increase fetal maturity without increasing
      the risk to the mother.

PMID- 11965220
TI  - Masticatory behavior in individuals with temporomandibular disorders.
AB  - BACKGROUND: Masticatory behavior was investigated in a group of patients
      presenting with temporomandibular disorders (TMDs) and compared with a Control
      Group. The goal of study was also to assess if patients were capable of making
      judgements about chewing difficulties and intensity of pain. METHODS: A
      comprehensive examination protocol was used to gather data about signs and
      symptoms of temporomandibular disorders. Subjects under study were instructed to
      chew and images were recorded in a videocassette for further analysis. We used a
      category scale to evaluate intensity of pain and chewing difficulties in a group
      of 23 TMD patients and 23 controls independent of age, sex or socioeconomic
      status. Full dentures wearers were not included in this study. RESULTS: The
      results of this investigation demonstrated that the frequencies of difficulties
      to open the mouth wide, unilateral chewing and chewing difficulties were
      significantly more prevalent in the group of TMD patients as compared to the
      control. Bruxing behavior was more prevalent in TMD patients and the time to eat
      a cookie was significantly longer. Subjects were capable of making judgements
      about severity of pain and chewing difficulties. In the TMD Group, average of
      both judgements were the same or close when subgroups were divided according to
      chewing preference and location of pain. CONCLUSIONS: Based on the results of
      this study, we concluded that the chewing pattern in TMD patients cannot solely
      be considered as a response to the location of pain and dysfunction.

PMID- 11965221
TI  - [Fluoride release properties of GRACs. A survey of the literature].
AB  - While numerous publications have documented the anticariogenic properties of
      GPACs through fluoride release measurements and artificial caries studies,
      considerable debate still exists concerning the fluoride release properties of
      these materials in terms of dissolution and diffusion mechanisms. This paper will
      review some of the more important aspects of GPAC fluoride release. Numerous
      studies have reported on the fluoride release properties of GPACs. The first
      point to note is that all the studies were performed on commercial materials.
      This approach has inherent difficulties as the main factor governing fluoride
      release is the GPAC composition and formulation. Traditional GPACs are two
      component systems, consisting essentially of a ion leachable
      fluoroaluminosilicate glass and a polymeric acid, especially a polycarboxylic
      acid; fluoride ions are of prime importance in this reaction, in that they have a
      major influence on the structure of the glass, its reactivity, cement formation
      and bioactivity. GPACs may be viewed as particle reinforced polymeric composites,
      in which the degraded residual glass particles with their silicious layer
      reinforce the polysalt matrix, improving mechanical properties.

PMID- 11965222
TI  - [Gorlin's syndrome. Case report].
AB  - The authors present a case of Gorlin's Syndrome, more satisfactorily defined as
      nevoid basal cell carcinoma syndrome (NBCS), a rare genetic disorder
      characterized mainly by multiple basal cell carcinomas and odontogenic
      keratocysts and other less frequent skeletal, sexual and neurological
      manifestations. Patient 75 years old, male. Previously treated surgically for
      multiple cutaneous basal cell carcinomas, comes to our Department to remove a
      suspected asymptomatic keratocyst. Clinical examination reveals cutaneous
      alterations of hands and feet (webbed hands and feet), a little progenism and
      multiple nevi and basal cell carcinomas on the body and the head. The oral cavity
      is free of alterations or clinical signs. NBCS is probably caused by chromosomal
      abnormalities of chromosome 5 and 9. The abnormalities seen in the latter are
      similar to those seen in people exposed for long periods to UV radiation. These
      abnormalities could determine malignant cutaneous tumors removing anti neoplastic
      protection. The association with odontogenic keratocysts, however not clearly
      understood, appears in more than 90% of cases. All the other disorders are less
      frequent. Juvenile basal cell carcinomas, especially if associated with
      odontogenic keratocysts suggest, the hypothesis of NBCS; if confirmed, this
      diagnosis makes further familial investigations necessary, to diagnose other
      cases, at the time unknown.

PMID- 11965224
TI  - Unusual vascular hamartoma of the hard palate. A case report.
AB  - Hamartomas are tumour-like malformations usually present since birth or which may
      develop during puberty. Hamartomas are related to anatomical development errors.
      Hamartomas are rarely found in the head and neck district. The case of an unusual
      vascular hamartoma localised in the hard palate of a 50-year-old female with no
      significant medical or family history is reported. Surgical treatment was
      performed by means of an excisional biopsy.

PMID- 11965223
TI  - Stevens-Johnson syndrome presumably induced by bromhexine. A case report.
AB  - The Stevens-Johnson syndrome is a serious form of erythema multiforme, an acute
      inflammatory pathology with an autoimmune pathogenesis. Its etiology is unknown,
      although it is thought to have multifactorial causes; nonetheless, many drugs are
      thought to induce such an immune response. The clinical symptomatology is mainly
      muco-cutaneous, with a remarkable oral involvement. The authors describe here a
      case of Stevens-Johnson syndrome involving the ocular, oral, and genital areas,
      presumably induced by the bromhexine administered to the patient for a viral
      syndrome.

PMID- 11965225
TI  - Anti-aromatase agents in the treatment and prevention of breast cancer.
AB  - Anti-aromatase agents now have a central role in the management of breast cancer
      in postmenopausal women; they are superior to megestrol acetate as second-line
      therapy and to tamoxifen for initial therapy of metastatic disease. They also are
      highly active as neoadjuvant therapy. Two classes of anti-aromatase agents are
      available: steroidal (eg, exemestane) and nonsteroidal (eg, anastrozole,
      letrozole). Although both types of agents act on the aromatase enzyme, they do so
      by different mechanisms and have different effects on cellular aromatase
      activity. Nonsteroidal agents are associated with increased aromatase enzyme
      content and steroidal agents are associated with decreased content. The increase
      in aromatase content seen with the nonsteroidal agents may in part explain the
      development of resistance with these agents and the ability of the steroidal
      agent exemestane to induce a response when nonsteroidal agents fail. Because the
      anti-aromatase agents almost completely eliminate endogenous estrogen production,
      they not only affect breast cancer tissues, but also may alter the function of
      other estrogen-responsive tissues. However, preclinical data show that the
      steroidal agent exemestane may actually improve bone and lipid metabolism. In
      addition, no increase in clinical fracture rate has been noted in women treated
      with exemestane in metastatic trials; the fracture risk has not yet been studied
      following prolonged exposure in healthy women. Exemestane associated beneficial
      effects on these end organs may be due to the steroidal nature of both the parent
      compound and its principal metabolite, 17-hydroexemestane. Similar benefits have
      not been reported with nonsteroidal antiaromatase agents. Based on their
      excellent activity in the metastatic setting, anti-aromatase agents are now being
      evaluated in the adjuvant setting and in pilot studies for chemoprevention. These
      studies will provide long-term data in healthy women and will help to
      differentiate anti-aromatase agents, in terms of their efficacy in the treatment
      of breast cancer and their effects on end organs.

PMID- 11965226
TI  - Endocrine and clinical endpoints of exemestane as neoadjuvant therapy.
AB  - A series of in vitro and in vivo studies have been performed to establish the
      endocrine and clinical endpoints of the type I anti-aromatase agent exemestane in
      neoadjuvant therapy. In vitro studies demonstrated a dose-related inhibition of
      aromatase activity with exemestane, even when activity was measured in a system
      in which the aromatase enzyme was induced in fibroblasts preincubated with
      exemestane but assayed in the absence of the drug. In contrast, type II anti
      aromatase agents (eg, aminoglutethimide, anastrozole, and letrozole) often caused
      a paradoxical increase in aromatase activity when measured under similar
      conditions. In vivo and in situ studies were performed in 12 postmenopausal women
      with untreated large or locally advanced estrogen receptor-rich tumors. The
      effect of exemestane 25 mg daily for 3 months on aromatization peripherally and
      in breast cancer and surrounding normal tissue was determined. Immediately before
      starting therapy, patients received an 18-hour infusion of radioactively labeled
      androgen and estrogen, followed by a wedge biopsy. This procedure was repeated
      after 3 months of treatment with exemestane, and the data were used to calculate
      peripheral and local aromatization. Changes in tumor volume were based on
      clinical examination, ultrasound, and mammography. Exemestane treatment was
      associated with a marked reduction in aromatization peripherally and in
      nonmalignant breast tissue in every patient and in breast tumor in all but one
      patient. Median reduction in tumor volume was 85.5% for clinical examination,
      82.5% for ultrasound, and 84% for mammography. Eight of 10 patients who would
      have required mastectomy before treatment were able to undergo breast-conserving
      surgery after treatment. Clinical benefits were accompanied by a marked reduction
      in cellular proliferation and progesterone receptor expression. These data
      support the use of exemestane in neoadjuvant therapy of breast cancer in
      postmenopausal women.

PMID- 11965227
TI  - The expanding role of epirubicin in the treatment of breast cancer.
AB  - Adjuvant treatment of early breast cancer has experienced major changes in the
      last 25 years. Since the mid 1970s, when cyclophosphamide, methotrexate and
      fluorouracil (CMF) resulted in statistically significant and clinically
      meaningful improvements in disease-free and overall survival, the use of adjuvant
      chemotherapy has become common practice worldwide. Anthracyclines are considered
      to be among the most active available agents to treat breast cancer and have
      become core components of adjuvant regimens. Anthracycline-containing
      polychemotherapy regimens provide a significant benefit over CMF. Regimens
      containing epirubicin are generally associated with prolongation in relapse-free
      and overall survival rates compared with standard therapies including CMF.
      Epirubicin-taxane combinations are active in treating metastatic breast cancer
      and do not appear to be associated with any pharmacokinetic interactions. Ongoing
      research is focusing on combining anthracyclines with taxanes in an effort to
      continue to improve outcomes following adjuvant therapy.

PMID- 11965229
TI  - Clinical experience with angiogenesis signaling inhibitors: focus on vascular
      endothelial growth factor (VEGF) blockers.
AB  - Angiogenesis is required for tumor growth and metastasis and, therefore,
      represents an exciting target for cancer treatment. Angiogenesis is a complex
      process that is tightly regulated by pro- and anti-angiogenic growth factors.
      Physiologic angiogenesis takes place during tissue growth and repair, during the
      female reproductive cycle, and during fetal development. Pathologic angiogenesis
      is characterized by either excessive (eg, cancer) or inadequate (eg, coronary
      artery disease) neovascularization. Angiogenesis occurs in a series of complex
      and interrelated steps that involve the release of pro-angiogenic growth factors,
      such as vascular endothelial growth factor (VEGF). VEGF regulates both vascular
      proliferation and permeability, and functions as an anti-apoptotic factor for
      newly formed blood vessels. The biological effects of VEGF are mediated by two
      receptors, VEGF-1 and VEGF-2, whose expression is largely limited to the vascular
      endothelium. VEGF is often expressed in tumors at substantially increased levels.
      It is expressed in response to hypoxia, oncogenes, and other cytokines, and its
      expression is associated with poor prognosis in several types of cancer. Several
      different strategies have been used to inhibit VEGF, including anti-VEGF
      monoclonal antibodies (eg, bevacizumab) and agents that inhibit the VEGF receptor
      (eg, SU5416). Both types of agents have tolerable side effects and have shown
      promise when evaluated in a wide range of tumor types. Angiogenesis, the role of
      VEGF in angiogenesis and malignancy, and strategies for cancer treatment with
      VEGF inhibitors are discussed.

PMID- 11965228
TI  - Celecoxib: a specific COX-2 inhibitor with anticancer properties.
AB  - In addition to the well-established pathophysiological role that COX-2 plays in
      inflammation, recent evidence implies that this isoform may also be involved in
      multiple biologic events throughout the tumorigenic process. Many epidemiological
      studies demonstrate that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the
      risk of a wide range of tumors. Further, COX-2 is chronically overexpressed in
      many premalignant, malignant, and metastatic human cancers, and levels of
      overexpression have been shown to significantly correlate to invasiveness,
      prognosis, and survival in some cancers. Pharmacological studies consistently
      demonstrate that COX-2 inhibitors dose-dependently inhibit tumor growth and
      metastasis in various relevant animal models of cancer. Importantly, several
      investigators have also shown COX-2 inhibitors may act additively or
      synergistically with currently used cytotoxics and molecularly targeted agents.
      Here we present a broad overview of the growing evidence that COX-2 plays a
      pivotal role throughout oncogenesis and summarize the rationale to explore the
      use of COX-2 inhibitors for the prevention and/or treatment of cancer as a single
      agent or in combination with current anticancer modalities.

PMID- 11965230
TI  - Immunotherapy of hematologic malignancies: the road to the future.

PMID- 11965231
TI  - Radioimmunotherapy for acute leukemia.
AB  - BACKGROUND: The use of monoclonal antibodies to deliver radioactive isotopes
      directly to tumor cells has become a promising strategy to enhance the antitumor
      effects of native monoclonal antibodies. In this article, we summarize the role
      of radioimmunotherapy in the treatment of leukemia. METHODS: The authors reviewed
      the published clinical trials of radioimmunotherapy in acute leukemia. RESULTS:
      Radioimmunoconjugates that emit beta-particles, such as 131I-anti-CD33, 90Y-anti
      CD33, 131I-anti-CD45, and 188Re-anti-CD66c, deliver significant doses of
      radiation to the bone marrow and may be particularly effective when used as part
      of a conditioning regimen for hematopoietic stem cell transplantation.
      Radioimmunoconjugates that emit short-ranged alpha-particles, such as 213Bi-anti
      CD33, are better suited for the treatment of low-volume or residual disease.
      CONCLUSIONS: Radiolabeled antibodies can be administered safely to patients with
      advanced leukemias and have significant antileukemic activity. Radiolabeled
      antibodies can potentially intensify the antileukemic effects of conditioning
      regimens when used in conjunction with hematopoietic stem cell transplantation.
      Whether or not radiolabeled antibodies improve the outcome of patients with
      leukemia remains to be demonstrated by randomized studies.

PMID- 11965233
TI  - Donor lymphocyte infusions to treat hematologic malignancies in relapse after
      allogeneic blood or marrow transplantation.
AB  - BACKGROUND: Patients with hematologic malignancies in relapse after allogeneic
      bone marrow transplantation can be treated by infusing leukocytes from the
      original stem cell donor. METHODS: The published literature on donor lymphocyte
      infusion (DLI) was reviewed. RESULTS: DLI induces complete remissions in the
      majority of patients with chronic myeloid leukemia (CML) in early-stage relapse
      and in less than 30% of patients with relapsed acute leukemia, myelodysplasia,
      and multiple myeloma. DLI-induced remissions of chronic phase CML are durable,
      but as many as half of patients with other diseases ultimately relapse.
      Complications of DLI include acute and chronic graft-vs-host disease (GVHD) and
      aplasia, which induce profound immunosuppression and susceptibility to
      opportunistic infections. There is a strong correlation of GVHD and disease
      response. CONCLUSIONS: Novel methods of augmenting the antitumor efficacy of DLI
      and of dissociating the graft-vs-leukemia effect from GVHD are needed. These
      studies will require an improved understanding of the cellular and molecular
      mechanisms of alloreactivity and the development of novel agents to control the
      nature and intensity of the alloimmune response.

PMID- 11965232
TI  - T-cell therapy of leukemia.
AB  - BACKGROUND: The demonstration that immune-mediated elimination of leukemia
      contributes to the success of allogeneic hematopoietic stem cell transplantation
      (HSCT) has renewed interest in the development of immune-based therapies that
      might be used to augment the antileukemic effect of HSCT or in patients who are
      not receiving HSCT. METHODS: The authors reviewed studies that have analyzed the
      mechanisms that may be operative in T-cell recognition of leukemia after
      allogeneic HSCT, identified candidate target antigens for immunotherapy of
      leukemia in transplant and nontransplant patients, and evaluated expression of
      candidate antigens on leukemic progenitors. RESULTS: A large number of potential
      targets for T-cell therapy or vaccination have now been identified in human
      leukemia. Studies to evaluate novel immune-based therapies are now being
      initiated. CONCLUSIONS: The rapid pace of progress in cellular and molecular
      immunology has identified new opportunities for developing T-cell therapy or
      vaccination for leukemia. Obstacles must be addressed before these approaches can
      be applied broadly, but the promising results of preclinical studies suggest
      continued efforts in this area will result in the establishment of immunotherapy
      as a useful modality in clinical practice.

PMID- 11965235
TI  - Future of monoclonal antibodies in the treatment of hematologic malignancies.
AB  - BACKGROUND: The approval of monoclonal antibodies (MAbs) as antibody-targeted
      therapy in the management of patients with hematologic malignancies has led to
      new treatment options for this group of patients. The ability to target
      antibodies to novel functional receptors can increase their therapeutic efficacy.
      METHODS: The authors reviewed improvements in MAb design to enhance their
      effectiveness over the existing therapeutic MAb currently approved for treating
      hematologic malignancies. RESULTS: Three classes of therapeutic MAbs showing
      promise in human clinical trials for treatment of hematologic malignancies
      include unconjugated MAb, drug conjugates in which the antibody preferentially
      delivers a potent cytotoxic drug to the tumor, and radioactive immunotherapy in
      which the antibody delivers a sterilizing dose of radiation to the tumor.
      CONCLUSIONS: A better appreciation of how MAbs are metabolized in the body and
      localized to tumors is resulting in the development of new antibody constructs
      with improved biodistribution profiles.

PMID- 11965236
TI  - NTP Toxicity Studies of Sodium Cyanide (CAS No. 143-33-9) Administered by Dosed
      Water to F344/N Rats and B6C3F1 Mice.
AB  - Cyanide and its salts are used extensively in industry and manufacturing and are
      found in water and food consumed by humans. Chronic exposure to low levels of
      cyanide is suspected to be responsible for various neuropathic and thyrotoxic
      conditions in humans. Data in the literature indicate that long-term exposure to
      near-lethal concentrations of cyanide may produce lesions in rodents similar to
      those linked to chronic cyanide exposure in humans. However, few data are
      available on the effects of subchronic exposure to cyanide concentrations that
      are not acutely toxic. To address this lack of data, 13-week toxicity studies on
      cyanide were conducted with male and female F344/N rats and B6C3F1 mice
      administered low doses of sodium cyanide in drinking water. Animals were
      evaluated for histopathology, clinical chemistry, hematology, urine chemistry,
      and reproductive toxicity. In addition, the mutagenicity of sodium cyanide was
      assessed in Salmonella typhimurium. Groups of 10 rats and 10 mice per sex were
      administered sodium cyanide in drinking water at concentrations of 0, 3, 10, 30,
      100, and 300 ppm for 13 weeks. No deaths attributed to sodium cyanide
      administration occurred in either species. In animals exposed to 300 ppm, male
      rats had slightly lower final mean body weights and mean body weight gains and
      female mice had slightly lower final mean body weights than the respective
      controls. Water consumption by rats and mice in the 100 and 300 ppm groups was
      10% to 30% lower than that by the controls; however, no clinical signs
      attributable to sodium cyanide administration or to dehydration were observed. No
      gross or microscopic changes specifically related to cyanide toxicity occurred at
      any site in males or females of either species. In particular, no lesions were
      found in the brain or thyroid gland. Differences between absolute and relative
      organ weights of exposed and control animals were minor and sporadic and were not
      exposure concentration dependent; these differences were not considered to be
      related to sodium cyanide administration. Hematologic, clinical chemistry, and
      urinalysis evaluations of rats and mice revealed minimal changes that were not
      considered biologically significant, although the decreased urine volume and
      increased urine specific gravity observed in male rats in the 300 ppm group of
      the supplemental clinical pathology study were consistent with the observed
      decreases in water consumption. The concentration of urinary thiocyanate (the
      primary metabolite of cyanide) increased with increasing exposure concentration
      at all time points. Sperm motility and vaginal cytology examinations were
      performed on rats and mice in the 0, 30, 100, and 300 ppm groups. Sodium cyanide
      caused a slight reduction in cauda epididymal weight in all groups of exposed
      male rats and in male mice exposed to 300 ppm. In male rats, the number of
      spermatid heads per testis in the 300 ppm group was less than the number in the
      controls, and sperm motility in all exposed groups was marginally lower than in
      the controls. Sodium cyanide produced no adverse effects on estrous cyclicity in
      female mice, but at higher concentrations (100 and 300 ppm), sodium cyanide
      caused a significant increase in the amount of time spent by female rats in
      proestrus and diestrus relative to estrus and metestrus. Sodium cyanide was not
      mutagenic in Salmonella typhimurium strain TA100, TA1535, TA97, or TA98 with or
      without exogenous metabolic activation. In summary, administration of low
      concentrations of sodium cyanide in drinking water to rats and mice for 13 weeks
      resulted in no clinically significant body weight, organ weight, histopathologic,
      or clinical pathology changes. The absorption of administered cyanide was
      confirmed by increases in urinary thiocyanate excretion. Concentrations of 100
      ppm and greater resulted in reduced water consumption. Thus, higher
      concentrations of sodium cyanide could not be administered by the drinking water
      route of administration. Alterations in reproductive parameters indicate that
      subchronic exposure to low concentrations of sodium cyanide may produce mild but
      significant adverse effects on rat reproductive systems. These changes are
      probably insufficient to decrease fertility in rats; however, humans are
      considered to be relatively more sensitive to such changes than rats, and the
      potential for reproductive toxicity in humans from low concentrations of cyanide
      warrants further investigation. NOTE: These studies were supported in part by
      funds from the Comprehensive Environmental Response, Compensation, and Liability
      Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic
      Substances and Disease Registry, U.S. Public Health Service.

PMID- 11965234
TI  - Cancer vaccines for hematologic malignancies.
AB  - BACKGROUND: Improvements in the identification of tumor-associated antigens and
      in our understanding of the mechanisms regulating antitumor immune responses have
      revived interest in the use of therapeutic cancer vaccination. Due to their
      unique characteristics, hematologic malignancies represent an ideal target for
      vaccine-based therapeutic interventions. METHODS: A review of published vaccine
      studies in experimental models as well as the results of clinical trials using
      vaccines for patients with hematologic tumors is presented. RESULTS: Tumor
      vaccine strategies can be divided into two categories: antigen-specific
      strategies, in which the tumor antigens have been identified and can be isolated
      to develop a molecularly defined vaccine, and cellular or non-antigen-specific,
      in which the tumor-specific antigens are unknown but presumed to exist within the
      material used to generate the vaccine. Early clinical trials have shown not only
      the feasibility and safety of either approach but also the obstacles in
      therapeutic cancer vaccination as an effective treatment modality for hematologic
      malignancies. CONCLUSIONS: Active immunization using current cancer vaccine
      approaches is feasible and safe. Although no major successes have been reported,
      the positive clinical results observed in some patients support the potential for
      therapeutic cancer vaccination in the management of hematologic malignancies.
      Results of studies that are testing vaccine formulations, targets, and settings
      (eg, bone marrow transplantation) may support the use of cancer vaccination as an
      efficient therapeutic strategy against tumors of hematologic origin.

PMID- 11965237
TI  - NTP Toxicity Studies of Sodium Selenate and Sodium Selenite (CAS Nos. 13410-01-0
      and 10102-18-8) Administered in Drinking Water to F344/N Rats and B6C3F1 Mice.
AB  - Sodium selenate and sodium selenite are used as supplements to poultry and
      livestock feed to promote growth and prevent selenium deficiency diseases. Both
      compounds have been found in chemical waste sites. Thirteen-week toxicity studies
      were conducted by administering the chemicals to groups of male and female F344/N
      rats and B6C3F1 mice in drinking water. Animals were evaluated for hematology,
      clinical chemistry, urinalysis (rats only), histopathology, and reproductive
      system effects. In the studies of sodium selenate, groups of 10 male and 10
      female rats and mice received 0, 3.75, 7.5, 15, 30, or 60 ppm sodium selenate for
      13 weeks. These concentrations were estimated to deliver 0, 0.1, 0.2, 0.4, 0.6,
      1.1 (males), or 0.8 (females) mg selenium/kg body weight for rats and 0, 0.3,
      0.5, 0.8, 1.5, or 2.6 mg/kg selenium for mice. All male and female rats exposed
      to 60 ppm died. The final mean body weights of rats exposed to 30 ppm sodium
      selenate and of mice exposed to 30 or 60 ppm were 13% to 29% lower than those of
      the controls. Water consumption by rats and mice exposed to 15 ppm or greater was
      decreased. Decreases in urine volume and increases in erythrocyte counts,
      hematocrit, hemoglobin concentrations, alanine aminotransferase activities, urea
      nitrogen, and urine specific gravity were considered related to dehydration, as
      indicated by the decreased water consumption and mean body weights in groups
      showing these differences. Administration of 7.5 ppm sodium selenate or greater
      was associated with increased incidences of renal papillary degeneration in rats.
      Dehydration may have been a contributing factor. No lesions related to sodium
      selenate administration occurred in mice. In the studies of sodium selenite,
      groups of 10 male and 10 female rats and mice received 0, 2, 4, 8, 16, or 32 ppm
      sodium selenite for 13 weeks. These concentrations were estimated to deliver 0,
      0.08, 0.13, 0.2, 0.4, 0.8 (males), or 0.9 (females) mg/kg selenium for rats and
      0, 0.14, 0.3, 0.5, 0.9, or 1.6 mg/kg selenium for mice. Two female rats exposed
      to 32 ppm died during the study. The final mean body weights of rats and mice
      exposed to 32 ppm were 17% to 54% lower than those of the controls. Water
      consumption by exposed rats and mice decreased with increasing exposure
      concentration. Changes in hematology, clinical chemistry, and urinalysis
      parameters similar to those observed in rats exposed to sodium selenate were
      observed in rats exposed to sodium selenite. These effects were also considered
      related to dehydration, as indicated by the decreased water consumption and mean
      body weights in exposed groups. Sodium selenite administration was associated
      with increased incidences of renal papillary regeneration in rats. Dehydration
      may have been a contributing factor. No lesions related to sodium selenite
      administration occurred in mice. Based on mortality in rats, body weight
      depression, and renal lesions, sodium selenate and sodium selenite were more
      toxic to rats than to mice. These chemicals caused increases in estrous cycle
      length in rats; sodium selenite also caused an increase in estrous cycle length
      in mice. Based on mortality, body weight depression, decreased water consumption,
      and renal papillary lesions, the estimated no-observed-adverse-effect level
      (NOAEL) in rats was 0.4 mg selenium/kg body weight for sodium selenate and for
      sodium selenite. Based on body weight depression and decreased water consumption,
      the estimated NOAEL in mice was 0.8 mg selenium/kg body weight for sodium
      selenate and 0.9 mg selenium/kg body weight for sodium selenite. NOTE: These
      studies were supported in part by funds from the Comprehensive Environmental
      Response, Compensation, and Liability Act trust fund (Superfund) by an
      interagency agreement with the Agency for Toxic Substances and Disease Registry,
      U.S. Public Health Service.

PMID- 11965238
TI  - NTP Toxicity Studies of Cadmium Oxide (CAS No. 1306-19-0) Administered by
      Inhalation to F344/N Rats and B6C3F1 Mice.
AB  - Three thousand tons of cadmium are imported or produced annually in the United
      States, and approximately 90% of this is cadmium oxide. Cadmium oxide is used in
      batteries, electroplating baths, pigments, plastics, synthetic products, and a
      variety of other materials. Cadmium oxide was nominated for study by the National
      Cancer Institute because of its widespread use and to obtain toxicity and
      carcinogenicity information. This report describes toxicity studies of cadmium
      oxide aerosol in F344/N rats and B6C3F1 mice, including sperm motility and
      vaginal cytology evaluations, and developmental toxicity studies of cadmium oxide
      aerosol in Sprague-Dawley rats and Swiss (CD-1(R)) mice. Genetic toxicology
      studies were done in Salmonella typhimurium and B6C3F1 mice erythrocytes. Cadmium
      oxide has been evaluated by other investigators for long-term carcinogenic
      effects, and recently the International Agency for Research on Cancer (IARC)
      evaluated cadmium and cadmium compounds for carcinogenic risks to humans. IARC
      (1993) classified cadmium and cadmium compounds as human carcinogens (Group I
      chemicals). GENETIC TOXICITY: Cadmium oxide was not mutagenic in Salmonella
      typhimurium strains TA98, TA100, TA1535, or TA1537, with or without exogenous
      metabolic activation, and did not induce micronuclei in erythrocytes of mice
      exposed by inhalation for 13 weeks. DEVELOPMENTAL TOXICITY STUDIES: For these
      studies, sperm-positive Sprague-Dawley rats and Swiss (CD-1(R)) mice were exposed
      to 0, 0.05, 0.5, or 2 mg/m(3) cadmium oxide 6 hours per day, 7 days per week, on
      gestation Day 4 through 19 (rats) or gestation Day 4 through 17 (mice). Maternal
      toxicity was observed in Sprague-Dawley rats exposed to 2 mg/m(3) cadmium oxide
      for 16 days and included body weights lower than those of the controls and
      clinical signs of toxicity (dyspnea and hypoactivity). There was no evidence of
      embryolethality in rats at any exposure level. However, in rats exposed to 2
      mg/m(3), developmental toxicity was evidenced by lower fetal weights and a
      significant increase in the incidence of reduced skeletal ossifications. Maternal
      toxicity was also observed in Swiss (CD-1(R)) mice exposed to 2 mg/m(3) cadmium
      oxide for 14 days. Clinical signs were dyspnea, hypoactivity, lower body weight,
      and a lower pregnancy rate (30% vs. 97% in the control group). The total number
      of resorptions per litter was increased at the 2 mg/m(3) level. Developmental
      toxicity was evidenced by lower fetal weights in the 0.5 and 2 mg/m(3) groups and
      an increase in the incidence of reduced sternebral ossification in the 2 mg/m(3)
      group. TOXICITY STUDIES: Male and female F344/N rats and B6C3F1 mice were exposed
      to cadmium oxide aerosol (MMAD=1.1-1.6 mm) for 6 hours per day, 5 days per week,
      for 2 or 13 weeks. Exposure levels were 0.1 to 10 mg/m(3) for the 2-week studies
      and 0.025 to 1 mg/m(3) for the 13-week studies. The current Occupational Safety
      and Health Administration (OSHA) standards for cadmium, based on the results of
      these and other studies, are 2.5 mg/m(3) for the action level (AL) and 5 mg/m(3)
      for the permissible exposure limit (PEL) (29 CFR &sec; 1910.1027). The AL and PEL
      are calculated as an 8-hour, time-weighted average exposure. In the 2-week
      studies, all rats and mice at the highest exposure level (10 mg/m(3)) died from
      respiratory toxicity characterized by inflammation, necrosis, and fibrosis of the
      lung. Toxicity to the nasal cavity and tracheobronchial lymph nodes was also
      observed in the 10 mg/m(3) groups. At the lower exposure levels, treatment
      related toxic lesions were not life threatening, and all body weights were within
      10% of controls. In the 13-week studies, all rats and mice (with the exception of
      one control mouse) survived to the end of the studies. The final mean body weight
      of rats in the highest exposure groups (1 mg/m(3)) was 93% of the control value.
      For all other exposed rat and mouse groups, final mean body weights corresponded
      to those of the respective controls. For rats and mice in the 13-week studies,
      the major toxicity was to the respiratory system. Treatment-related lesions were
      observed in the lung, tracheobronchial lymph node, larynx, and nose. The no
      observed-adverse-effect level (NOAEL) in the lungs was 0.025 mg/m(3) for rats. A
      NOAEL was not found in the lungs or larynx of mice or in the larynx of rats. At
      the 0.025 and 0.05 mg/m(3) levels in mice, lung lesions were minimal and not
      considered life threatening. A NOAEL in the nasal cavity was 0.05 mg/m(3) for
      rats and mice. Reproductive toxicity was observed in the 1 mg/m(3) groups of rats
      and was evidenced by a reduced number of spermatids per testis and an increase in
      the length of the estrous cycle. Reproductive toxicity was not observed at any
      exposure level in mice.

PMID- 11965239
TI  - NTP Toxicity Studies of beta-Bromo-beta-Nitrostyrene (CAS No. 7166-19-0)
      Administered by Gavage to F344/N Rats and B6C3F1 Mice.
AB  - beta-Bromo-beta-nitrostyrene is a wide-spectrum biocide most frequently used as a
      fungicide to combat the formation of slime in paper and pulp mill operations.
      Toxicity studies were conducted by administering beta-bromo-beta-nitrostyrene
      (99% pure, trans isomer) to groups of 10 male and 10 female F344/N rats and
      B6C3F1 mice by gavage, 5 days per week for 4 weeks. Doses of 0, 37, 75, 150, 300,
      or 600 mg/kg were administered in a corn oil vehicle. The parameters evaluated
      included hematology, clinical chemistry (rats only), and histopathology. The
      genetic toxicity of b-bromo-b- nitrostyrene was evaluated in Salmonella
      typhimurium and in peripheral blood erythrocytes of mice. In addition, the
      absorption, distribution, metabolism, and excretion of b-bromo-b- nitrostyrene
      were studied in male F344 rats following intravenous, dermal, or oral
      administration. In the 4-week study in rats, two males in the 150 mg/kg group,
      one male and one female in the 300 mg/kg groups, and all rats in the 600 mg/kg
      groups died or were killed moribund before the end of the study. The mean body
      weight gains and absolute and relative thymus weights of male and female rats in
      the 300 mg/kg groups were lower than those of the controls. Hematology
      evaluations in rats indicated the development of a mild anemia and monocytosis
      consistent with and likely related to inflammatory and ulcerative lesions that
      occurred in the gastrointestinal tract. Clinical chemistry evaluations indicated
      lower alkaline phosphatase activities and serum total protein and albumin
      concentrations in treated rats than in the controls. Treatment-related lesions in
      rats were observed in the forestomach, glandular stomach, cecum, nasal passages,
      and testis. Males were generally affected at lower doses than females. The most
      prominent lesions were in the forestomach and were characterized by inflammation,
      hemorrhage, and necrosis in rats dying early. In rats surviving to the end of the
      study, forestomach lesions included necrosis, ulceration, and regenerative
      epithelial hyperplasia and hyperkeratosis. Inflammation of the glandular stomach
      and cecum also occurred in rats dying early. Inflammation and degeneration of the
      nasal passage in treated rats were attributed to reflux of the irritant chemical
      in the gavage fluid. Testicular degeneration was seen in rats dying early and was
      characterized by necrotic germ cells and a decreased number of spermatozoa in the
      epididymal tubules and by multinucleated syncytial cells in the seminiferous
      tubules. In the 4-week study in mice, one male in the 300 mg/kg group and all
      mice in the 600 mg/kg groups died or were killed moribund before the end of the
      study. No significant changes in final mean body weights or mean body weight
      gains were observed in males or females. Hematologic changes consistent with
      inflammatory lesions occurred in male and female mice in the 300 mg/kg groups.
      Treatment-related lesions in mice occurred in the forestomach, gallbladder, and
      testis. Forestomach lesions were similar to those described in rats and were only
      present in male and female mice given doses of 300 mg/kg or greater. At these
      dose levels, inflammation and degeneration/necrosis of the gallbladder mucosa
      also occurred in male and female mice, but these lesions were absent in the bile
      ducts or liver. Testicular degeneration occurred in mice dying early and was
      similar to that observed in rats. In comparative disposition and metabolism
      studies in male F344 rats, clear differences were found between the fate of b
      bromo- b-nitrostyrene following oral administration and the fate of radiolabeled
      beta-bromo-beta-nitrostyrene following intravenous or dermal administration. Oral
      exposure resulted in significant absorption of nonhydrolyzed beta-bromo-beta
      nitrostyrene and the formation of parent compound metabolites, primarily 1-phenyl
      2-nitroethyl-1-sulfonic acid (PNSA), a product of a sulfation reaction at the
      alpha carbon. Following dermal exposure, a limited amount of beta-bromo-beta
      nitrostyrene entered the systemic circulation (approximately 10% per 24 hours
      from a 10 mg/cm2 dose) although lower doses were more completely absorbed. Once
      beta-bromo-beta-nitrostyrene entered the circulation, significant amounts of the
      dose were hydrolyzed or bound to macromolecules. PNSA was not a major metabolite
      in dermal or intravenous studies. Regardless of the route of administration, only
      low levels of radioactive label from beta-bromo-beta-nitrostyrene were retained
      in tissues following exposure, and most beta-bromo-beta-nitrostyrene metabolites
      were excreted in the urine and feces within 24 to 48 hours. beta-bromo-beta
      nitrostyrene was mutagenic in S. typhimurium strains TA98 and TA100 in the
      absence of exogenous metabolic activation (S9). No mutagenic activity was
      observed with S9 in either of these strains, and no mutagenic activity was
      observed in strains TA97 or TA1535, with or without S9. The frequency of
      micronucleated normochromatic erythrocytes was significantly increased in the
      peripheral blood of male mice, but not female mice, following 4 weeks of exposure
      to beta-bromo-beta-nitrostyrene by corn oil gavage. In summary, under the
      conditions of these 4-week gavage studies, rats were more sensitive to the toxic
      and irritant effects of beta-bromo-beta-nitrostyrene than mice, and males were
      more affected by beta-bromo-beta-nitrostyrene than females. Although the specific
      cause of the early deaths could not be determined, significant inflammation and
      necrosis developed in the forestomach of rats and mice, in the glandular stomach
      and cecum of rats, and in the gallbladder of mice. Similar lesions in the nasal
      passages of rats were attributed to reflux of gavage materials. The no-observed-
      adverse-effect level (NOAEL) for histopathologic lesions was 37 mg/kg per day for
      rats and 150 mg/kg per day for mice.

PMID- 11965240
TI  - NTP Technical Report on the Toxicity Studies of 1,1,1-Trichloroethane (CAS No. 71
      55-6) Administered in Microcapsules in Feed to F344/N Rats and B6C3F1 Mice.
AB  - 1,1,1-Trichloroethane is a widely used solvent in industry and in household
      products such as cleaning agents, wallpaper and carpet glues, carpets, spray and
      solid insecticides, and rodenticides. 1,1,1-Trichloroethane was studied because
      of its widespread use in industry and in the home and the potential for human
      exposure. Groups of 10 male and 10 female F344/N rats and B6C3F1 mice were given
      5,000, 10,000, 20,000, 40,000, or 80,000 ppm microencapsulated 1,1,1,
      trichloroethane in feed for 13 weeks. Groups of 10 male and 10 female rats and
      mice served as untreated controls and received feed without microcapsules;
      additional groups of 10 male and 10 female rats and mice served as vehicle
      controls and received feed with empty microcapsules. Animals were evaluated for
      clinical pathology (rats only), reproductive system effects, and histopathology.
      Genetic toxicity studies were conducted in Salmonella typhimurium, L5178Y mouse
      lymphoma cells, and cultured Chinese hamster ovary cells. In addition, peripheral
      blood slides from the mice in the 13-week study were analyzed for frequency of
      micronucleated erythrocytes. All rats survived to the end of the study. The final
      mean body weights of exposed rats were within 10% of those of the untreated and
      vehicle controls. Feed consumption by exposed groups of male and female rats was
      similar to that by the control groups, suggesting that the diet was palatable to
      the animals. Based on average feed consumption values, male rats ingested
      approximately 300, 600, 1,200, 2,400, or 4,800 mg 1,1,1-trichloroethane/kg body
      weight per day, and females received 300, 650, 1,250, 2,500, or 5,000 mg/kg per
      day. In general, changes in clinical pathology parameters were minor, sporadic,
      and inconsistent between males and females; these differences were not considered
      to be treatment related or biologically significant. The liver weights of female
      rats administered 80,000 ppm were significantly less than those of the untreated
      and vehicle controls. Male rats exposed to 10,000 ppm or greater had a spectrum
      of nonneoplastic kidney lesions consistent with hyaline droplet nephropathy. No
      treatment-related gross or microscopic lesions were observed in female rats.
      There were no exposure-related deaths in mice. Based on average feed consumption
      values, male mice ingested approximately 850, 1,770, 3,500, 7,370, or 15,000
      mg/kg per day, and female mice received 1,340, 2,820, 5,600, 11,125, or 23,000
      mg/kg per day. Even though feed consumption by exposed groups was slightly
      greater than that by the controls, the mean body weights of male and female mice
      administered 20,000 ppm or greater were significantly less than those of the
      untreated and vehicle controls. The heart, kidney, and lung weights of the
      vehicle control male mice were significantly greater than those of the untreated
      controls. There were no biologically significant differences in organ weights
      between exposed and control mice. No gross or microscopic lesions in male or
      female mice were attributed to chemical exposure. Epididymal spermatozoal
      concentrations of male rats and mice given 80,000 ppm were significantly less
      than those of the vehicle controls. 1,1,1-Trichloroethane was not mutagenic in
      Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537, with or without S9
      metabolic activation. In the mouse lymphoma assay for induction of
      trifluorothymidine resistance in L5178Y cells, 1,1,1-trichloroethane gave a
      negative response in one test (with and without S9) and an equivocal response in
      a second test (in the presence of S9). Results of a sister chromatid exchange
      test in cultured Chinese hamster ovary cells were considered to be equivocal due
      to an unrepeated questionable response obtained in the presence of S9 in a single
      trial; without S9, results were negative. 1,1,1-Trichloroethane induced
      chromosomal aberrations in cultured Chinese hamster ovary cells in the absence of
      S9; with S9, the increase in aberrations noted in a single trial was not
      significant. A small increase in the frequency of micronucleated normochromatic
      erythrocytes was noted in peripheral blood slides from male mice administered
      1,1,1-trichloroethane in feed for 13 weeks; the results were determined to be
      equivocal, while the female peripheral blood micronucleus test results were
      negative. In conclusion, 1,1,1-trichloroethane induced nonneoplastic lesions
      consistent with hyaline droplet nephropathy in male rats. Exposure to 1,1,1
      trichloroethane caused decreases in liver weights in female rats and decreases in
      mean body weights of male and female mice. The no-observed-adverse-effect level
      (NOAEL) was estimated to be 10,000 ppm for male and female rats and mice.

PMID- 11965241
TI  - Toxicity Studies of 1,3-Diphenylguanidine (CAS No. 102-06-7) Administered in Feed
      to F344/N Rats and B6C3F1 Mice.
AB  - 1,3-Diphenylguanidine (DPG) has been used as a primary and secondary accelerator
      in the vulcanization of rubber. Exposure to 1,3-diphenylguanidine may occur as a
      result of dermal contact during rubber manufacture or from contact with the
      finished products. DPG is poorly absorbed through skin. Therefore, to evaluate
      the toxicity associated with systemic exposure, 2-week and 13-week toxicology
      studies were conducted by administering DPG in feed to groups of male and female
      F344/N rats and B6C3F1 mice. Genetic toxicity was also evaluated in Salmonella
      typhimurium and in the micronucleus erythrocyte assay in peripheral blood from
      male and female mice. During 2-week studies, rats and mice received feed
      containing 0, 250, 500, 750, 1,500, or 3,000 ppm 1,3-diphenylguanidine. All rats
      and mice survived to the end of the study. Feed consumption and mean body weights
      of groups of rats that received 750, 1,500, or 3,000 ppm were lower than
      controls. No compound-related gross lesions were observed at the end of the
      study. The final mean body weight of female mice that received 3,000 ppm was 6%
      lower than the controls at the end of the study; however, no other effects
      attributable to chemical exposure were observed in mice. Based on these results
      the same exposure concentrations (0, 250, 500, 750, 1,500, and 3,000 ppm) were
      selected for the 13-week study; because of the poor palatability of the 750 ppm
      or higher dosed feed in rats, concentrations greater than 3,000 ppm were not
      considered appropriate. Six male rats and all female rats that received feed
      containing 3,000 ppm died or were killed moribund before the end of the 13-week
      study. Final mean body weights and feed consumption of male and female rats that
      received 1,500 or 3,000 ppm were lower than controls throughout the study. The
      values of several hematologic parameters were significantly different from the
      controls in groups of rats that received 1,500 or 3,000 ppm; however, these
      differences were attributable to reduced nutrient intake as a result of reduced
      feed consumption. Lower total serum protein, cholesterol, triglyceride, and
      creatinine concentrations were also considered to be the consequence of reduced
      nutrient intake. Alkaline phosphatase activity and bile acid concentrations were
      greater than the controls in most groups exposed to DPG and were considered to be
      an indication of cholestasis. Secretory depletion of the seminal vesicles and
      prostate gland, epididymal hypospermia, spermatogenic arrest, and significant
      reductions in the absolute weights of the prostate gland, seminal vesicles, and
      testis were observed in male rats in the 3,000 ppm group. Uterine hypoplasia
      characterized by a reduction in uterine size due to thinner and less developed
      endometrium was observed in female rats that received diets containing 750 ppm or
      greater. The mean length of the estrous cycle was greater in female rats that
      received 750 or 1,500 ppm feed than in the controls. All mice survived to the end
      of the 13-week study. Mean body weights of males and females that received feed
      containing 750, 1,500, or 3,000 ppm were lower than the controls. Reduced organ
      weights relative to control for mice that received 1,500 or 3,000 ppm were
      related to low body weights of these groups. In mice that received 3,000 ppm
      sperm motility was reduced and the number of spermatid heads was greater than for
      control males, and the estrous cycle length in females was longer than that of
      the controls. 1,3-Diphenylguanidine was tested for mutagenicity in Salmonella
      typhimurium strains TA98, TA100, TA1535, and TA1537 with and without S9 metabolic
      activation enzymes. No mutagenic activity was observed in the absence of S9. With
      S9, positive responses were observed in strains TA98 and TA100, and an equivocal
      response was observed in strain TA1537. Results of a peripheral blood
      micronucleus test in B6C3F1 mice were concluded to be negative in males and
      equivocal in females. In summary, consumption of feed containing 1,3
      diphenylguanidine for 2 weeks or 13 weeks was not associated with any histologic
      response which could be attributed to chemical exposure. Instead the observed
      changes were indicative of reduced nutrient intake and are consistent with
      similar changes observed in other studies of feed restricted rats and mice.

PMID- 11965242
TI  - NTP Comparative Toxicity Studies of o-, m-, and p-Chloroanilines (CAS Nos. 95-51
      2; 108-42-9; and 106-47-8) Administered by Gavage to F344/N Rats and B6C3F1 Mice.
AB  - Chlorinated anilines are used as intermediates in the manufacture of dyes, drugs,
      and agricultural agents. In comparative 13-week studies conducted to determine
      the structure-toxicity relationships of o-, m-, and p-chloroaniline, groups of 10
      male and 10 female F344/N rats and B6C3F1 mice were administered 0, 10, 20, 40,
      80, or 160 mg o- or m-chloroaniline per kilogram body weight in dilute
      hydrochloric acid by gavage. Animals were evaluated for hematology, clinical
      chemistry, histopathology, and reproductive system effects. Genetic toxicity
      studies of o- and m-chloroaniline in vivo and in vitro were also conducted. The
      results of the o- and m-chloroaniline studies were compared to results from the p
      chloroaniline studies performed previously under similar experimental conditions
      by the same laboratory; doses in the p-chloroaniline studies were 0, 5, 10, 20,
      40, and 80 mg/kg for rats and 0, 7.5, 15, 30, 60, and 120 mg/kg for mice. The
      hematopoietic system was the target of o-, m-, and p-chloroaniline in rats and
      mice. Neither the o- nor the p- isomer had an adverse effect on survival; the
      death of one female rat in the 160 mg/kg m-chloroaniline group during week 12 was
      possibly secondary to methemoglobinemia. The final mean body weights and weight
      gains of male rats in the highest dose group in each study and female mice in the
      160 mg/kg group in the o-chloroaniline study were significantly less than those
      of the respective controls. Clinical findings of toxicity included a transient
      bluish discoloration of the genital and footpad regions in rats administered o-
      or m-chloroaniline and tremors in rats and mice administered o-chloroaniline and
      in mice administered m-chloroaniline; these effects occurred primarily in the 80
      and 160 mg/kg groups. Methemoglobin concentrations were increased in dosed rats
      and mice in all studies and resulted in a secondary anemia; the severity of the
      anemia increased with increasing dose. Microscopic lesions considered related to
      chemical administration in rats and mice included hemosiderin pigmentation in the
      bone marrow, kidney, liver, and spleen; hematopoiesis in the liver and spleen;
      and erythroid cell hyperplasia in the bone marrow. These lesions reflected the
      response to hemolytic anemia and methemoglobinemia induced by the chloroanilines.
      A comparative analysis of the results suggests that p-chloroaniline is the most
      potent of the chloroaniline isomers in the induction of methemoglobin formation
      in rats and mice, followed by m-chloroaniline and then by o-chloroaniline. This
      order of potency was also observed for changes in other hematology parameters and
      in spleen weights, gross and microscopic lesions, and the severity of hemosiderin
      deposition. Although the o-, m-, and p- isomers of chloroaniline all exhibit
      genetic toxicity, the profiles of activity among the three isomers are not
      identical. p-Chloroaniline was mutagenic in all assays in which it was tested,
      including the Salmonella assay, the mouse lymphoma assay, in vitro Chinese
      hamster ovary cell cytogenetics assays, and the in vivo mouse bone marrow
      micronucleus assay; in contrast, o- and m-chloroaniline gave mixed results among
      the various assays in which each was tested. In conclusion, chloroaniline isomers
      are hematotoxic and have the same pattern of toxicity in rats and mice.
      Hematotoxicity occurred at all doses in these studies. p-Chloroaniline induces
      the most severe hematotoxic effect, followed by m-chloroaniline, then o
      chloroaniline. Each of the three isomers is more toxic to rats than to mice. p
      Chloroaniline is clearly genotoxic in various test systems, while the results for
      the o- and m- isomers are inconsistent and indicate weak or no genotoxic effects.

PMID- 11965243
TI  - Monte Carlo simulation of hyaluronidase reaction involving hydrolysis,
      transglycosylation and condensation.
AB  - The action of hyaluronidase on oligosaccharides from hyaluronan is complicated
      due to branched reaction paths containing hydrolysis, transglycosylation and
      condensation. The unit component of hyaluronan is a disaccharide, namely GlcA
      (beta 1-->3)-GlcNAc where GlcA and GlcNAc are d-glucuronic acid and d-N
      acetylglucosamine respectively. Hyaluronan is the linear polymer formed by these
      disaccharide units, linked together with beta 1-->4 glycosidic bonds. Bovine
      testicular hyaluronidase acts only at beta 1-->4 glycosidic bonds of hyaluronan.
      The progress of product distribution from short oligosaccharides was simulated
      with the Monte Carlo method using the probabilistic model. The model consists
      only of a single enzyme molecule and a finite number of substrate and water
      molecules. The simulation is based on a simple reaction scheme and proceeds via
      an algorithm with minimum adjustable parameters generating random numbers and
      probabilities. The experimental data for bovine testicular hyaluronidase using
      [GlcA-(beta 1-->3)-GlcNAc](4) as the starting substrate were quantitatively
      simulated with only three adjustable parameters. The simulated data for [GlcA
      (beta 1-->3)-GlcNAc](3) and [GlcA-(beta 1-->3)-GlcNAc](5) as the starting
      substrates agreed semi-quantitatively with experimental data using the same
      parameters. The mechanism of the hyaluronidase reaction is a combination of
      branched probabilistic cycles. The condensation reaction is much weaker than the
      transglycosylation reaction but contributes to product distribution at the final
      stage of the reaction, preventing complete hydrolysis of the substrates.

PMID- 11965245
TI  - Population extinction and recolonization in human demographic history.
AB  - For over 30 years, a debate has raged among anthropologists about the origins of
      anatomically modern humans. At first the debate centered on fossil evidence, but
      in the past 10-15 years population geneticists have entered the fray. One model,
      the multiregional evolution model, posits a gradual transition from Homo erectus
      to anatomically modern humans throughout the Old World. In contrast, the recent
      African origin model hypothesizes that anatomically modern humans arose from a
      small, isolated population in Africa, spread out of Africa, and replaced
      indigenous H. erectus populations in Eurasia and Australasia. A primary
      objection, from a population genetics perspective, to the multiregional model is
      that the genetic data suggest a small effective population size for humans. This
      effective size is on the order of 10,000. Effective population size has a complex
      relationship with census size, but it has been argued that, assuming that
      effective size is roughly equal to the number of breeding individuals in human
      populations under standard demographic conditions, 10,000 breeding individuals
      could not have occupied much of the Old World throughout the Pleistocene and
      remained a cohesive species via gene flow. However, this argument is not valid if
      one considers population extinction and recolonization, which might have played
      an important role in human history during the Pleistocene. With population
      extinction and recolonization, the inbreeding effective population size can be
      small and the census size extremely large. In this paper, I will show that under
      conditions of population extinction and recolonization, an effective population
      size of 10,000 suggested by genetic data is compatible with a large census size
      consistent with the multiregional model.

PMID- 11965246
TI  - Eigenvalue effective population numbers for populations that vary cyclically in
      size.
AB  - Four types of effective population numbers have been discussed in the literature
      on population genetics. It was shown by Wang and Pollak [Math. Biosci. 166 (2000)
      1] that if a large random mating dioecious population varies cyclically in size
      and the population is followed over a whole cycle, the variance, inbreeding and
      mutation effective numbers are equal. It was also shown, in a special case, that
      the variance effective number, N(eV), is equal to the eigenvalue effective
      number, N(eE). The former is related to the long-term rate at which the variance
      between lines increases and the latter is computed from the largest non-unit
      eigenvalue of the matrix of transition probabilities governing the change with
      time of frequencies of an allele among males and females. It is shown in this
      paper that N(eE) is quite generally at least approximately the same as N(eV) if
      the numbers of males and females are always large. Both autosomal and sex-linked
      loci are considered and the theory allows for reproduction partially by a regular
      system of inbreeding.

PMID- 11965244
TI  - Glycerol restores heat-induced p53-dependent apoptosis of human glioblastoma
      cells bearing mutant p53.
AB  - BACKGROUND: We have previously reported that glycerol acts as a chemical
      chaperone to restore the expression of WAF1 in some human cancer cell lines
      bearing mutant p53. Since the expression of WAF1 is up-regulated by activated
      wildtype p53, glycerol appears to restore wtp53 function. The aim of the present
      study is to examine the restoration of heat-induced p53-dependent apoptosis by
      glycerol in human glioblastoma cells (A-172) transfected with a vector carrying a
      mutant p53 gene (A-172/mp53 cells) or neo control vector (A-172/neo cells).
      RESULTS: A-172/mp53 cells showed heat resistance compared with A-172/neo cells
      but A-172/mp53 cells in turn became heat sensitive when pre-treated with glycerol
      before heat treatment. The accumulation of Bax in the A-172/mp53 cells was
      induced by heating with glycerol pre-treatment, but not without it, whereas the
      accumulation in the A-172/neo cells was induced in both cases. Furthermore, mp53
      extracted from heated cells came to bind to the sequence specific region after
      heating combined with glycerol pre-treatment. The phosphorylation of mp53 at
      serine15 was suppressed by an inhibitor of the phosphatidylinositol 3-kinase (PI3
      K) family. CONCLUSION: These results suggest that glycerol is effective in
      inducing conformational change of phosphorylated p53 and restoring mp53 to wtp53
      function, leading to enhanced heat sensitivity through the induction of
      apoptosis. This novel tool for enhancement of heat sensitivity in cancer cells
      bearing mp53 may be applicable for p53-targeted hyperthermia, because mutation or
      inactivation of p53 is observed in approximately 50% of human cancers.

PMID- 11965247
TI  - A contribution of sparse matrices tools to matrix population model analysis.
AB  - When one wants to study the dynamics of structured populations, matrix type
      models are widely used. The complexity of such models increases with the number
      of classes of individuals considered, and a mathematical analysis becomes
      difficult to perform when a further heterogeneous spatial structure is
      introduced. The use of efficient computational tools is also required for
      numerical simulations. In this note we deal with the contribution of sparse
      matrices tools which allow to numerically simulate and to numerically perform
      stability analysis of large sized structured population models including density
      dependence and spatial heterogeneities. Our main motivation through this work is
      to show that such numerical tools can be useful when mathematical methods become
      difficult to employ.

PMID- 11965249
TI  - Asynchronous exponential growth in an age structured population of proliferating
      and quiescent cells.
AB  - A model of a proliferating cell population is analyzed. The model distinguishes
      individual cells by cell age, which corresponds to phase of the cell cycle. The
      model also distinguishes individual cells by proliferating or quiescent status.
      The model allows cells to transit between these two states at any age, that is,
      any phase of the cell cycle. The model also allows newly divided cells to enter
      quiescence at cell birth, that is, cell age 0. Sufficient conditions are
      established to assure that the cell population has asynchronous exponential
      growth. As a consequence of this asynchronous exponential growth the population
      stabilizes in the sense that the proportion of the population in any age range,
      or the fraction in proliferating or quiescent state, converges to a limiting
      value as time evolves, independently of the age distribution and proliferating or
      quiescent fractions of the initial cell population. The asynchronous exponential
      growth is proved by demonstrating that the strongly continuous linear semi-group
      associated with the partial differential equations of the model is positive,
      irreducible, and eventually compact.

PMID- 11965248
TI  - Numerical integration of autonomous and non-autonomous non-linear size-structured
      population models.
AB  - We present an efficiency study for autonomous and non-autonomous non-linear size
      structured population models. The study considers three numerical methods: a
      characteristics scheme, the Lax-Wendroff method and the box method, which are
      completely described in the paper. Five test problems are considered with diverse
      degree of complexity: non-trivial equilibrium, periodic solutions and diverse
      growth functions. The study of the efficiency takes into account the properties
      of the numerical schemes (such as the stability) and uses a multiple regression
      analysis to determine the constants of the leading terms of the corresponding
      global errors. We show how the tables of errors and cpu-times can be used to
      explain the meaning of the efficiency results. In addition, we present the
      convergence analysis of the box method.

PMID- 11965250
TI  - Variability in the timing of G(1)/S transition.
AB  - Cell cycle duration and phase transition times are not fixed, even within
      homogeneous cell populations growing under optimal environmental conditions. We
      investigate G(1) phase variability from the molecular point of view and propose a
      mathematical approach to model the protein interactions regulating the transition
      from the G(1) phase to the phase of DNA synthesis. The mathematical model has
      some connections with flow cytometry experimental data.

PMID- 11965251
TI  - Cell kinetics in tumour cords studied by a model with variable cell cycle length.
AB  - A mathematical model is developed that describes the proliferative behaviour at
      the stationary state of the cell population within a tumour cord, i.e. in a
      cylindrical arrangement of tumour cells growing around a blood vessel and
      surrounded by necrosis. The model, that represents the tumour cord as a
      continuum, accounts for the migration of cells from the inner to the outer zone
      of the cord and describes the cell cycle by a sequence of maturity compartments
      plus a possible quiescent compartment. Cell-to-cell variability of cycle phase
      transit times and changes in the cell kinetic parameters within the cord, related
      to changes of the microenvironment, can be represented in the model. The
      theoretical predictions are compared against literature data of the time course
      of the labelling index and of the fraction of labelled mitoses in an experimental
      tumour after pulse labelling with 3H-thymidine. It is shown that the presence of
      cell migration within the cord can lead to a marked underestimation of the actual
      changes along cord radius of the kinetics of cell cycle progression.

PMID- 11965252
TI  - A size-structured, non-conservative ODE model of the chemostat.
AB  - We study a class of size-structured, ODE models of growth in the chemostat, that
      take into account cell maintenance and substrate dependent cell mortality. Unlike
      most classical chemostat models, they are supposed to be non-conservative, in the
      sense that they do not verify the mass conservation principle. However, using a
      change of time scale, we are able to obtain qualitative results. Then, using a
      Lyapunov functional, we prove the global stability of the non-trivial
      equilibrium. Some examples of the possible structure of the models are given to
      finish with.

PMID- 11965253
TI  - Parameter identification in dynamical models of anaerobic waste water treatment.
AB  - Biochemical reactions can often be formulated mathematically as ordinary
      differential equations. In the process of modeling, the main questions that arise
      are concerned with structural identifiability, parameter estimation and practical
      identifiability. To clarify these questions and the methods how to solve them, we
      analyze two different second order models for anaerobic waste water treatment
      processes using two data sets obtained from different experimental setups. In
      both experiments only biogas production rate was measured which complicates the
      analysis considerably. We show that proving structural identifiability of the
      mathematical models with currently used methods fails. Therefore, we introduce a
      new, general method based on the asymptotic behavior of the maximum likelihood
      estimator to show local structural identifiability. For parameter estimation we
      use the multiple shooting approach which is described. Additionally we show that
      the Hessian matrix approach to compute confidence intervals fails in our examples
      while a method based on Monte Carlo Simulation works well.

PMID- 11965254
TI  - Bayesian predictiveness, exchangeability and sufficientness in bacterial
      taxonomy.
AB  - We present a theory of classification and predictive identification of bacteria.
      Bacterial strains are characterized by a binary vector and the taxonomy is
      specified by attaching a label to each vector. The theory is developed from only
      two basic assumptions, viz. that the sequence of pairs of feature vectors and the
      attached labels is judged (infinitely) exchangeable and predictively sufficient.
      We derive expressions for the training error and the probability of
      identification error and show that latter is an affine function of the former. We
      prove the law of large numbers for identification matrices, which contain the
      fundamental information of bacterial data. We prove the Bayesian risk consistency
      of the predictive identification rule given by the theory and show that the
      training error is a consistent estimate of the generalization error.

PMID- 11965255
TI  - A predator-prey model with predators using hawk and dove tactics.
AB  - In this work we present a predator-prey model that incorporates individual
      behavior of the predators. A classical Lotka-Volterra model with self-limiting
      prey describes the predator-prey interaction. Predator individuals can use two
      behavioral tactics to dispute a prey when they meet, the classical hawk and dove
      tactics. Each individual can use both tactics along its life. The predator
      behavioral change is described by means of a game dynamic model based upon the
      replicator equations, where the gain depends on prey density. We assume that the
      demographic process, predator-prey interactions, acts at a slow time scale in
      comparison with the evolution of the behavior of the predator population. The
      existence of two time scales allows studying the complete system from a reduced
      one, which describes the dynamics of the total predator and prey densities at the
      slow time scale. The aim of this work is to study the effects of individual
      predator behavior on the dynamics of the predator-prey system. The main
      conclusion that emerges from this study is the existence of a relationship
      between prey density and the strategy adopted by predators: aggressive behavior
      is connected to high prey and low predator densities, whereas a polymorphism dove
      hawk is found at low prey and high predator densities.

PMID- 11965256
TI  - Numerical bifurcation analysis of a tri-trophic food web with omnivory.
AB  - We study the consequences of omnivory on the dynamic behaviour of a three species
      food web under chemostat conditions. The food web consists of a prey consuming a
      nutrient, a predator consuming a prey and an omnivore which preys on the predator
      and the prey. For each trophic level an ordinary differential equation describes
      the biomass density in the reactor. The hyperbolic functional response for single
      and multi prey species figures in the description of the trophic interactions.
      There are two limiting cases where the omnivore is a specialist; a food chain
      where the omnivore does not consume the prey and competition where the omnivore
      does not prey on the predator. We use bifurcation analysis to study the long-term
      dynamic behaviour for various degrees of omnivory. Attractors can be equilibria,
      limit cycles or chaotic behaviour depending on the control parameters of the
      chemostat. Often multiple attractor occur. In this paper we will discuss
      community assembly. That is, we analyze how the trophic structure of the food web
      evolves following invasion where a new invader is introduced one at the time.
      Generally, with an invasion, the invader settles itself and persists with all
      other species, however, the invader may also replace another species. We will
      show that the food web model has a global bifurcation, being a heteroclinic
      connection from a saddle equilibrium to a limit cycle of saddle type. This global
      bifurcation separates regions in the bifurcation diagram with different
      attractors to which the system evolves after invasion. To investigate the
      consequences of omnivory we will focus on invasion of the omnivore. This
      simplifies the analysis considerably, for the end-point of the assembly sequence
      is then unique. A weak interaction of the omnivore with the prey combined with a
      stronger interaction with the predator seems advantageous.

PMID- 11965257
TI  - Variable effort harvesting models in random environments: generalization to
      density-dependent noise intensities.
AB  - In a previous paper [Math. Biosci. 156 (1999) 1], we have studied quite general
      stochastic differential equation models for the growth of populations subjected
      to harvesting in a random environment. We have obtained conditions for non
      extinction and for the existence of stationary distributions (as well as
      expressions for such distributions) similar to conditions for non-extinction and
      for the existence of a stable equilibrium in the corresponding deterministic
      model. The models were quite general, considering density-dependent natural
      growth functions and harvesting policies of very general form, so that our
      results would be model independent and provide minimal requirements for the
      choice of a wise density-dependent harvesting policy. Those models, however,
      although quite general on all other respects, have a serious limitation. In fact,
      the ways environmental fluctuations affect the population per capita growth rate
      are poorly known and those models only considered two possible ways, namely the
      noise intensity could be constant or proportional to that rate. To overcome this
      limitation, in this paper we generalize the previous results to density-dependent
      positive noise intensities of very general form so that they also become
      independent from the way environmental fluctuations affect population growth
      rates.

PMID- 11965258
TI  - Genetic models for plant pathosystems.
AB  - Deterministic, discrete time, genetics models for a resistant plant host and a
      virulent pathogen are developed and analyzed. The original model was developed by
      Leonard in 1977 for a single gene with haploid pathogens and diploid hosts [Ann.
      N.Y. Acad. Sci. 287 (1977) 207]. The original model is generalized to diploid
      hosts and pathogens with incomplete dominance of the heterozygote. In addition,
      the single gene model is extended to two genes and a stochastic model with random
      selection values is formulated and simulated. It is shown using local stability
      properties that stability of the polymorphic equilibrium is indeterminant; the
      equilibrium is non-hyperbolic. The original model of Leonard has this same
      property. However, with random selection values, solutions tend to converge
      toward the polymorphic equilibrium.

PMID- 11965259
TI  - Schistosomiasis models with density dependence and age of infection in snail
      dynamics.
AB  - New models for schistosomiasis are developed. These models incorporate several
      realistic features including drug treatment for human hosts, an infection age in
      snail hosts, density-dependent birth rate of snails, distribution of schistosomes
      within human hosts, and disease-induced mortality in both human and snail hosts.
      The qualitative and quantitative mathematical properties of the models are
      studied, their biological consequences and some control strategies are discussed,
      and the results of the new models are compared with those of simpler models. It
      is shown that the new model may have a bifurcation at which the unique endemic
      equilibrium changes the stability and stable periodic solutions exist. This is
      quite different from the simpler models. Explicit thresholds of treatment rate
      are established above which the infection will be controlled under certain
      levels. Evaluations of cost-effectiveness are also discussed by analyzing the
      sensitivity of the mean number of parasites per person to changes of other
      parameters.

PMID- 11965260
TI  - Determination of threshold conditions for a non-linear stochastic partnership
      model for heterosexually transmitted diseases with stages.
AB  - When comparing the performance of a stochastic model of an epidemic at two points
      in a parameter space, a threshold is said to have been crossed when at one point
      an epidemic develops with positive probability; while at the other there is a
      tendency for an epidemic to become extinct. The approach used to find thresholds
      in this paper was to embed a system of ordinary non-linear differential equations
      in a stochastic process, accommodating the formation and dissolution of marital
      partnerships in a heterosexual population, extra-marital sexual contacts, and
      diseases such as HIV/AIDS with stages. A symbolic representation of the Jacobian
      matrix of this system was derived. To determine whether this matrix was stable or
      non-stable at a particular parameter point, the Jacobian was evaluated at a
      disease-free equilibrium and its eigenvalues were computed. The stability or non
      stability of the matrix was then determined by checking if all real parts of the
      eigenvalues were negative. By writing software to repeat this process for a
      selected set of points in the parameter space, it was possible to develop search
      engines for finding points in the parameter space where thresholds were crossed.
      The results of a set of Monte Carlo simulation experiments were reported which
      suggest that, by combining the stochastic and deterministic paradigms within a
      single formulation, it was possible to obtain more informative interpretations of
      simulation experiments than if attention were confined solely to either paradigm.

PMID- 11965261
TI  - Vaccination strategies and backward bifurcation in an age-since-infection
      structured model.
AB  - We consider models for a disease with acute and chronic infective stages, and
      variable infectivity and recovery rates, within the context of a vaccination
      campaign. Models for SIRS and SIS disease cycles exhibit backward bifurcations
      under certain conditions, which complicate the criteria for success of the
      vaccination campaign by making it possible to have stable endemic states when
      R(0)<1. We also show the extent to which the forms of the infectivity and
      recovery functions affect the possibility of backward bifurcations. SIR and SI
      models examined do not exhibit this behavior.

PMID- 11965262
TI  - Optimal vaccination policies for stochastic epidemics among a population of
      households.
AB  - This paper considers stochastic epidemics among a population partitioned into
      households, with mixing locally within households and globally throughout the
      population. The two levels of mixing have important implications for the
      threshold behaviour of the epidemic and consequently for the form and
      construction of optimal vaccination policies. Optimality is considered in terms
      of the cost of the vaccination program, the form of which is general enough to
      include costs of the vaccine itself, its administration, travel to and/or contact
      with the households. New explicit results are obtained by a constructive method
      which explain the form of optimal vaccination policies. Numerical studies are
      presented which exemplify the results discussed.

PMID- 11965263
TI  - On the evolutionary coexistence of parasite strains.
AB  - Classical models of parasite competition show that coexistence is impossible if
      different strains give complete cross-immunity. However, parasite coexistence is
      possible if some of the model assumptions are changed. For instance, coexistence
      is impossible if density-dependence operates only in hosts' fertility, but
      surprisingly becomes possible if hosts' mortality is density-dependent. Parasite
      strains can also coexist if a host already infected with one strain may become
      infected by another strain (superinfection). I examine here if these reasons for
      coexistence carry over to evolutionary timescales: in other words, suppose that
      potentially a continuum of parasite strains may arise by mutations; will
      evolution arrive at a halt? in that case, will only one or several strains
      persist? The paradigm and methods of adaptive dynamics are used in this study. It
      is found, under reasonably general assumptions, that a unique evolutionarily
      stable state for virulence, alpha(*), exist for both models. However, the pattern
      of the invasibility plots depends on the shape of the trade-off (between
      virulence and transmissibility, or superinfection rates) functions, and on the
      host demography. In many cases, the state alpha(*) is evolutionarily stable only
      with respect to small mutations, not to larger ones; hence, evolutionary dynamics
      will bring virulence to alpha(*) only if mutations are sufficiently small; for
      larger mutations, evolutionary dynamics are more complex and still mainly
      unresolved.

PMID- 11965264
TI  - Failure to address the health toll of the Middle East crisis.

PMID- 11965265
TI  - The IONA study: preparing the myocardium for ischaemia?

PMID- 11965266
TI  - Gene-expression profiling to classify soft-tissue sarcomas.

PMID- 11965267
TI  - Tobacco industry and EC advertising ban.

PMID- 11965268
TI  - Galantamine for vascular dementia: some answers, some questions.

PMID- 11965269
TI  - Lessons from the UK sigmoidoscopy screening trial.

PMID- 11965270
TI  - More pathophysiologically oriented treatment of GORD?

PMID- 11965271
TI  - Effect of nicorandil on coronary events in patients with stable angina: the
      Impact Of Nicorandil in Angina (IONA) randomised trial.
AB  - BACKGROUND: In addition to its anti-ischaemic effects, the antianginal drug
      nicorandil is thought to have cardioprotective properties. We did a randomised
      trial to find out whether nicorandil could reduce the frequency of coronary
      events in men and women with stable angina and additional risk factors. METHODS:
      5126 patients were randomly assigned 20 mg nicorandil twice daily (n=2565) or
      identical placebo (n=2561) in addition to standard antianginal therapy. The
      primary composite endpoint was coronary heart disease death, non-fatal myocardial
      infarction, or unplanned hospital admission for cardiac chest pain. The secondary
      endpoint was the combined outcome of coronary heart disease death or non-fatal
      myocardial infarction. Other outcomes reported include all-cause mortality, all
      cardiovascular events, and acute coronary syndromes. Mean follow-up was 1.6 years
      (SD 0.5). Analysis was by intention to treat. FINDINGS: There were 398 (15.5%)
      primary endpoint events in the placebo group and 337 (13.1%) in the nicorandil
      group (hazard ratio 0.83, 95% CI 0.72-0.97; p=0.014). The frequency of the
      secondary endpoint was not significantly different between the groups (134 events
      [5.2%] vs 107 events [4.2%]; 0.79, 0.61-1.02; p=0.068). The rate of acute
      coronary syndromes was 195 (7.6%) in the placebo group and 156 (6.1%) in the
      nicorandil group (0.79, 0.64-0.98; p=0.028), and the corresponding rates for all
      cardiovascular events were 436 (17.0%) and 378 (14.7%; 0.86, 0.75-0.98; p=0.027).
      INTERPRETATION: We showed a significant improvement in outcome due to a reduction
      in major coronary events by antianginal therapy with nicorandil in patients with
      stable angina.

PMID- 11965272
TI  - Epidural anaesthesia and analgesia and outcome of major surgery: a randomised
      trial.
AB  - BACKGROUND: Epidural block is widely used to manage major abdominal surgery and
      postoperative analgesia, but its risks and benefits are uncertain. We compared
      adverse outcomes in high-risk patients managed for major surgery with epidural
      block or alternative analgesic regimens with general anaesthesia in a multicentre
      randomised trial. METHODS: 915 patients undergoing major abdominal surgery with
      one of nine defined comorbid states to identify high-risk status were randomly
      assigned intraoperative epidural anaesthesia and postoperative epidural analgesia
      for 72 h with general anaesthesia (site of epidural selected to provide optimum
      block) or control. The primary endpoint was death at 30 days or major
      postsurgical morbidity. Analysis by intention to treat involved 447 patients
      assigned epidural and 441 control. FINDINGS: 255 patients (57.1%) in the epidural
      group and 268 (60.7%) in the control group had at least one morbidity endpoint or
      died (p=0.29). Mortality at 30 days was low in both groups (epidural 23 [5.1%],
      control 19 [4.3%], p=0.67). Only one of eight categories of morbid endpoints in
      individual systems (respiratory failure) occurred less frequently in patients
      managed with epidural techniques (23% vs 30%, p=0.02). Postoperative epidural
      analgesia was associated with lower pain scores during the first 3 postoperative
      days. There were no major adverse consequences of epidural-catheter insertion.
      INTERPRETATION: Most adverse morbid outcomes in high-risk patients undergoing
      major abdominal surgery are not reduced by use of combined epidural and general
      anaesthesia and postoperative epidural analgesia. However, the improvement in
      analgesia, reduction in respiratory failure, and the low risk of serious adverse
      consequences suggest that many high-risk patients undergoing major intra
      abdominal surgery will receive substantial benefit from combined general and
      epidural anaesthesia intraoperatively with continuing postoperative epidural
      analgesia.

PMID- 11965273
TI  - Efficacy of galantamine in probable vascular dementia and Alzheimer's disease
      combined with cerebrovascular disease: a randomised trial.
AB  - BACKGROUND: Vascular dementia is the second commonest form of dementia, and
      vascular factors contribute to the development of dementia in many patients with
      Alzheimer's disease. Galantamine amplifies the acetylcholine response by
      inhibiting acetylcholinesterase and modulating nicotinic receptors. It has shown
      broad, sustained benefits in patients with Alzheimer's disease. We investigated
      the effects of galantamine in patients with a diagnosis of probable vascular
      dementia or Alzheimer's disease combined with cerebrovascular disease. METHODS:
      Eligible patients were randomly assigned galantamine 24 mg/day (n=396) or placebo
      (n=196) in a multicentre, double-blind, 6-month trial. Primary endpoints were
      cognition (Alzheimer's disease assessment scale, cognitive subscale [ADAS-cog])
      and global functioning (clinician's interview-based impression of change plus
      caregiver input [CIBIC-plus]). Secondary endpoints included assessments of
      activities of daily living and behavioural symptoms. Patients were monitored for
      adverse events. Analyses were on the basis of observed case or last observation
      carried forward. FINDINGS: Galantamine showed greater efficacy than placebo on
      ADAS-cog (galantamine change -1.7 [SE 0.4] vs placebo 1.0 [0.5]; treatment effect
      2.7 points; p<0.0001) and CIBIC-plus (213 [74%] vs 95 [59%] patients remained
      stable or improved, p=0.0001). Activities of daily living and behavioural
      symptoms were also significantly improved compared with placebo (p=0.002 and
      p=0.016, respectively). Galantamine was well tolerated. INTERPRETATION:
      Galantamine showed a therapeutic effect on all key areas of cognitive and non
      cognitive abilities in this group of dementia patients.

PMID- 11965274
TI  - Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline
      findings of a UK multicentre randomised trial.
AB  - BACKGROUND: This randomised controlled trial is examining the hypothesis that a
      single flexible sigmoidoscopy screening offered at around age 60 years can lower
      the incidence and mortality of colorectal cancer. We report here on
      acceptability, safety, feasibility, and yield. METHODS: Men and women aged 55-64
      years, in 14 UK centres, who responded to a mailed questionnaire that they would
      attend for flexible sigmoidoscopy screening if invited, were randomly assigned
      screening or control (ratio one to two). The control group was not contacted.
      Small polyps were removed during screening, and colonoscopy was undertaken if
      high-risk polyps (three or more adenomas, size 1 cm or greater, villous, severely
      dysplastic, or malignant) were found. FINDINGS: Of 354,262 people asked about
      their interest in having flexible sigmoidoscopy screening, 194,726 (55%)
      responded positively, and 170,432 eligible individuals were randomised.
      Attendance among those assigned screening was 71% (40,674 of 57,254). 2131 (5%)
      were classified as high-risk and referred for colonoscopy; 38,525 with no polyps
      or only low-risk polyps detected were discharged. Distal adenomas were detected
      in 4931 (12.1%) and distal cancer in 131 (0.3%). Proximal adenomas were detected
      in 386 (18.8% of those undergoing colonoscopy) and proximal cancer in nine cases
      (0.4%). 62% of cancers were Dukes' stage A or locally excised. There was one
      perforation after flexible sigmoidoscopy and four after colonoscopy. An average
      of 48 people were screened, and two or three colonoscopy referrals generated, per
      centre each week. Interpretation Our flexible sigmoidoscopy screening regimen is
      acceptable, feasible, and safe. The prevalence of neoplasia is high, and
      colonoscopy referral rates of 5% are acceptable.

PMID- 11965275
TI  - Lipoid pneumonia.

PMID- 11965276
TI  - Molecular characterisation of soft tissue tumours: a gene expression study.
AB  - BACKGROUND: Soft-tissue tumours are derived from mesenchymal cells such as
      fibroblasts, muscle cells, or adipocytes, but for many such tumours the
      histogenesis is controversial. We aimed to start molecular characterisation of
      these rare neoplasms and to do a genome-wide search for new diagnostic markers.
      METHODS: We analysed gene-expression patterns of 41 soft-tissue tumours with
      spotted cDNA microarrays. After removal of errors introduced by use of different
      microarray batches, the expression patterns of 5520 genes that were well defined
      were used to separate tumours into discrete groups by hierarchical clustering and
      singular value decomposition. FINDINGS: Synovial sarcomas, gastrointestinal
      stromal tumours, neural tumours, and a subset of the leiomyosarcomas, showed
      strikingly distinct gene-expression patterns. Other tumour categories--malignant
      fibrous histiocytoma, liposarcoma, and the remaining leiomyosarcomas--shared
      molecular profiles that were not predicted by histological features or
      immunohistochemistry. Strong expression of known genes, such as KIT in
      gastrointestinal stromal tumours, was noted within gene sets that distinguished
      the different sarcomas. However, many uncharacterised genes also contributed to
      the distinction between tumour types. INTERPRETATION: These results suggest a new
      method for classification of soft-tissue tumours, which could improve on the
      method based on histological findings. Large numbers of uncharacterised genes
      contributed to distinctions between the tumours, and some of these could be
      useful markers for diagnosis, have prognostic significance, or prove possible
      targets for treatment.

PMID- 11965277
TI  - A hoarse voice.

PMID- 11965278
TI  - Quantification of the completeness of follow-up.
AB  - Completeness of follow-up is important, especially in clinical trials, since
      unequal follow-up in the treatment groups can bias the analysis of results. In
      survival studies, information on participants who do not complete the study is
      often omitted because their data can be included up to the time at which they
      were lost to follow-up. We propose a simple measure of completeness that is the
      ratio of the total observed person-time and the potential person-time of follow
      up in a study. Our measure is easy to calculate, can be illustrated pictorially,
      and can be used to identify subgroups with especially poor follow-up.

PMID- 11965279
TI  - Protective effects of the sickle cell gene against malaria morbidity and
      mortality.
AB  - The high frequency of the sickle-cell haemoglobin (HbS) gene in malaria endemic
      regions is believed to be due to a heterozygote (HbAS) advantage against fatal
      malaria. Data to prospectively confirm the protection associated with HbAS
      against mortality are lacking. We show that HbAS provides significant protection
      against all-cause mortality, severe malarial anaemia, and high-density
      parasitaemia. This significant reduction in mortality was detected between the
      ages of 2 and 16 months, the highest risk period for severe malarial anaemia in
      this area. These data are important in understanding the role of malaria in the
      selection and maintenance of the sickle cell gene.

PMID- 11965280
TI  - Effect of vitamin A supplementation on measles-specific antibody levels in Guinea
      Bissau.
AB  - We have previously reported that vitamin A supplementation with measles vaccine
      at age 9 months increases measles-specific antibody concentrations in children at
      age 18 months compared with placebo. We examined these children when they reached
      age 6-8 years. Fewer vitamin A-supplemented children had non-protective antibody
      concentrations (p=0.0095); among children with protective antibody levels,
      vitamin A-supplemented children tended to have higher geometric mean antibody
      titres (p=0.09). Thus, simultaneous administration of vitamin A and measles
      vaccine at age 9 months had a long-term effect on measles-specific antibody
      levels and may contribute to improved measles control in less-developed
      countries.

PMID- 11965281
TI  - Controversy over deliberate conception of deaf child.

PMID- 11965283
TI  - Maternal autoantibodies might trigger autoimmune diabetes.

PMID- 11965286
TI  - What future for the Argentine science base after last year's economic collapse?

PMID- 11965287
TI  - Africa looks to new breed of rice to combat food shortages.

PMID- 11965289
TI  - Older people must be on the health and development policy agenda.

PMID- 11965294
TI  - Tobacco industry strategies for influencing European Community tobacco
      advertising legislation.
AB  - Restrictions on tobacco company advertising and sponsorship are effective parts
      of tobacco control programmes worldwide. Through Council Directive 98/43/EC, the
      European Community (EC) sought to end all tobacco advertising and sponsorship in
      EC member states by 2006. Initially proposed in 1989, the directive was adopted
      in 1998, and was annulled by the European Court of Justice in 2000 following a
      protracted lobbying campaign against the directive by a number of interested
      organisations including European tobacco companies. A new advertising directive
      was proposed in May, 2001. We reviewed online collections of tobacco industry
      documents from US tobacco companies made public under the US Master Settlement
      Agreement of 1998. Documents reviewed dated from 1978 to 1994 and came from
      Philip Morris, R J Reynolds, and Brown and Williamson (British American Tobacco)
      collections. We also obtained approximately 15,000 pages of paper records related
      to British American Tobacco from its documents' depository in Guildford, UK. This
      information was supplemented with information in the published literature and
      consultations with European tobacco control experts. The tobacco industry lobbied
      against Directive 98/43/EC at the level of EC member state governments as well as
      on a pan-European level. The industry sought to prevent passage of the directive
      within the EC legislature, to substitute industry-authored proposals in place of
      the original directive, and if necessary to use litigation to prevent
      implementation of the directive after its passage. The tobacco industry sought to
      delay, and eventually defeat, the EC directive on tobacco advertising and
      sponsorship by seeking to enlist the aid of figures at the highest levels of
      European politics while at times attempting to conceal the industry's role. An
      understanding of these proposed strategies can help European health advocates to
      pass and implement effective future tobacco control legislation.

PMID- 11965295
TI  - Health consequences of intimate partner violence.
AB  - Intimate partner violence, which describes physical or sexual assault, or both,
      of a spouse or sexual intimate, is a common health-care issue. In this article, I
      have reviewed research on the mental and physical health sequelae of such
      violence. Increased health problems such as injury, chronic pain,
      gastrointestinal, and gynaecological signs including sexually-transmitted
      diseases, depression, and post-traumatic stress disorder are well documented by
      controlled research in abused women in various settings. Intimate partner
      violence has been noted in 3-13% of pregnancies in many studies from around the
      world, and is associated with detrimental outcomes to mothers and infants. I
      recommend increased assessment and interventions for intimate partner violence in
      health-care settings.

PMID- 11965297
TI  - Eradication of a disease: how we cured symptomless prostate cancer.

PMID- 11965296
TI  - Placebo-controlled trials and the Declaration of Helsinki.
AB  - A revised version of the Declaration of Helsinki, issued in October, 2000,
      remains a vital expression of medical ethics, and deserves unanimous support. A
      strict interpretation of the declaration seems to rule out clinical trials that
      use a placebo control group whenever licensed therapeutic methods already exist,
      preferring active controls. Although the efficacy of some new medicines can be
      satisfactorily established without the use of a placebo, for others the judicious
      use of placebo remains essential to establish their effectiveness.

PMID- 11965298
TI  - Absence of nasal bone and detection of trisomy 21.

PMID- 11965299
TI  - Absence of nasal bone and detection of trisomy 21.

PMID- 11965300
TI  - Absence of nasal bone and detection of trisomy 21.

PMID- 11965301
TI  - Absence of nasal bone and detection of trisomy 21.

PMID- 11965302
TI  - Absence of nasal bone and detection of trisomy 21.

PMID- 11965304
TI  - Wolbachia DNA recognition.

PMID- 11965305
TI  - Irritable bowel syndrome and coeliac disease.

PMID- 11965306
TI  - Irritable bowel syndrome and coeliac disease.

PMID- 11965307
TI  - Irritable bowel syndrome and coeliac disease.

PMID- 11965308
TI  - Treatment of hypoxaemia during one-lung ventilation with almitrine.

PMID- 11965309
TI  - Risk of venous thromboembolism and oral contraceptives.

PMID- 11965310
TI  - Risk of venous thromboembolism and oral contraceptives.

PMID- 11965311
TI  - Guidelines for acute coronary syndrome without ST elevation.

PMID- 11965312
TI  - Guidelines for acute coronary syndrome without ST elevation.

PMID- 11965313
TI  - Guidelines for acute coronary syndrome without ST elevation.

PMID- 11965315
TI  - Generic medicines are not substandard medicines.

PMID- 11965317
TI  - Motivation behind infant rape in South Africa.

PMID- 11965318
TI  - Intestinal permeability and coeliac disease.

PMID- 11965330
TI  - Ambling towards Nirvana.

PMID- 11965331
TI  - Policy relevant determinants of health: an international perspective.
AB  - BACKGROUND: International comparisons can provide clues to understanding some of
      the important policy-related determinants of health, including those related to
      the provision of health care services. An earlier study indicated that the
      strength of the primary care infrastructure of a health services system might be
      related to overall costs of health services. The purpose of the current research
      was to determine the robustness of the findings in the light of the passage of 5
      10 years, the addition of two more countries, and the findings of other research
      on the possible importance of other determinants of country health levels.
      METHODS: Thirteen industrialized countries, all with populations of at least 5
      million, were characterized by the relative strength of their primary care
      infrastructure, the degree of national income inequality, and a major
      manifestation of a behavioral determinant of health that is amenable to policy
      intervention (smoking), using international data sets and national informants.
      Health system and primary care practice characteristics were judged according to
      pre-set criteria. Major indicators of health were used as dependent variables, as
      were health care costs. FINDINGS: The stronger the primary care, the lower the
      costs. Countries with very weak primary care infrastructures have poorer
      performance on major aspects of health. Although countries that are intermediate
      in the strength of their primary care generally have levels of health at least as
      good as those with high levels of primary care, this is not the case in early
      life, when the impact of strong primary care is greatest. A subset of
      characteristics (equitable distribution of resources, publicly accountable
      universal financial coverage, low cost sharing, comprehensive services, and
      family-oriented services) distinguishes countries with overall good health from
      those with poor health at all ages. Neither income inequality nor smoking status
      accurately identified those countries with either consistently high or
      consistently poor performance on the health indicators. INTERPRETATION: A certain
      level of health care expenditures may be required to achieve overall good health
      levels, even in the presence of strong primary care infrastructures. Very low
      costs may interfere with achievement of good health, particularly at older ages,
      although very high levels of costs may signal excessive and potentially health
      compromising care. Five policy-relevant characteristics appear to be related to
      better population health levels. There is no consistent relationship between
      income inequality, smoking, and health levels as measured by various indicators
      of health in different age groups.

PMID- 11965332
TI  - Health status and work burden of Alzheimer patients' informal caregivers:
      comparisons of five different care programs in the European Union.
AB  - BACKGROUND: In 1998, a research study was conducted to compare existing programs
      in the European Union providing both care to people with senile dementia of the
      Alzheimer type, and support to their informal caregiver. METHOD: Five programs
      were selected in seven centres. Home social services (Denmark), Day centres
      (Germany), Expert Centres (Belgium, Spain), Group Living/Cantou (Sweden, France),
      Respite hospitalization (France). In each centre, 50 patients were randomly
      selected. The questionnaire addressed informal caregivers (or referents). It
      included the Nottingham Health Profile (NHP), the Zarit Scale, and it collected
      data on age, sex and position (spouse or child) of the informal caregiver, as
      well as age, level of mental deterioration and disabilities of the patient.
      RESULTS: (n=322 subjects) Comparatively with caregivers of Respite
      hospitalization patients chosen as the reference, caregivers of patients cared by
      Group living/Cantou and Home social services experienced a significantly lower
      burden. The benefit from the Expert centre program concerned emotional reactions
      (depression) (odds ratio=0.32; P=0.02) and work burden (Zarit) (OR=0.32; P=0.04).
      The main benefit for caregivers who received Day centre help was the important
      reduction of feelings of social isolation (OR=0.13; P=0.0003). CONCLUSIONS: The
      Group Living/Cantou program appeared as the most efficient way to reduce informal
      caregiver burden, independently from the country considered.

PMID- 11965333
TI  - Free choice of sickness funds in regulated competition: evidence from Germany and
      The Netherlands.
AB  - Sickness funds became the focal point of health insurance reforms in the 1990s.
      Policy makers expected funds to become more consumer-oriented and more active in
      managing the provision of health care. This is especially true for two countries
      in the heart of Europe that, on first view, have many similar institutional
      characteristics. Both Germany and The Netherlands have introduced competition
      between sickness funds in the last decade. We present extensive quantitative, as
      well qualitative, data with regard to the behaviour of consumers after the
      introduction of free choice between sickness funds. National data was used with
      regard to contribution rates and member flows and survey data was used to
      investigate personal motives for actual change and perception of differences
      between sickness funds. In Germany, contribution rates between sickness funds
      differ significantly. Accordingly, these differences are the main reason for
      consumers to switch funds, which occurs on a considerable scale. However, survey
      data show that other reasons may be important too. In The Netherlands, premium
      differences are much lower. The same is true for the degree of change. Survey
      data show that consumers perceive very small differences between sickness funds
      and do not see much reason for change. Our findings support the claim that the
      degree of actual changing depends strongly on economic incentives, especially
      with regard to the extent of financial risk sickness funds have to bear and to
      the extent premiums or contribution rates can differ. However, the higher the
      financial risk of individual sickness funds actually is, the higher the
      incentives for risk selection.

PMID- 11965334
TI  - A typology for provider payment systems in health care.
AB  - A typology to classify provider payment systems from an incentive point of view
      is developed. We analyse the way, how these systems can influence provider
      behaviour and, a fortiori, contribute to attain the general objectives of health
      care, i.e. quality of care, efficiency and accessibility. The first dimension of
      the typology indicates whether there is a link between the provider's income and
      his activity. In variable systems, the provider has an ability to influence his
      earnings, contrary to fixed systems. The second dimension indicates whether the
      provider's payments are related to his actual costs or not. In retrospective
      systems, the provider's own costs are the basis for reimbursement ex post whereas
      in prospective systems payments are determined ex ante without any link to the
      real costs of the individual provider. These different characteristics are likely
      to influence provider behaviour in different ways. Furthermore the most
      frequently used criteria to determine the provider's income are discussed: per
      service, per diem, per case, per patient and per period. Also a distinction is
      made between incentives at the level of the individual provider (micro-level) and
      the sponsor (macro-level). Finally, the potential interactions when several
      payment systems are used simultaneously are discussed. This typology is useful to
      classify and compare different types of payment systems as prevailing in
      different countries, and provides a useful framework for future research of
      health care payment systems.

PMID- 11965335
TI  - Women's knowledge of new regulations about publicly funded medications for
      osteoporosis.
AB  - To provide adequate and updated information regarding changes in health care
      regulations or policies can be a challenging task for policy makers. The aim of
      the present study was to examine knowledge about new regulations regarding
      publicly funded drugs for the treatment of osteoporosis in a group of 109 Israeli
      women. Participants were interviewed between 3 and 6 months after the new
      regulations were enacted. Although participants were aware of their eligibility,
      moderate levels of knowledge were found regarding the content of the regulations.
      Especially low levels of knowledge were found regarding the scope of services and
      the definition of osteoporosis according to the regulations. High-risk
      participants (i.e. older participants and those with lower T score or who had
      suffered a fracture) had no better knowledge of the regulations. The development
      of multifaceted information programs aimed at disseminating the content of policy
      changes is encouraged.

PMID- 11965336
TI  - The gatekeeper in vision care. An analysis of the co-ordination of professional
      services in The Netherlands.
AB  - Data from a national survey were used to explore the position of
      ophthalmologists, general practitioners, orthoptists, optometrists and opticians
      in the domain of vision care services. Options for organising the gatekeeper
      function were analysed. This was done on the basis of six cases that the five key
      occupations considered as their overlapping areas. Nearly all respondents
      reported to be consulted by patients with the given complaints, indicating rather
      unclear boundaries between the professions. Further, the opinions indicated
      preference for a medical gatekeeper (ophthalmologist, GP) rather than a non
      medical one (optometrist). Lack of agreement on suggested gatekeeper options
      suggest other options to consider, like regional networks of GPs,
      ophthalmologists, orthoptists and optometrists who share the responsibility for a
      specified client population. At present, such innovative arrangements are being
      introduced. GPs and optometrists could share the responsibility for gate-keeping
      and for referring patients to more specialised services.

PMID- 11965354
TI  - Chronic stress during prepubertal development: immediate and long-lasting effects
      on arterial blood pressure and anxiety-related behavior.
AB  - The present work was undertaken to study the immediate and long-lasting effects
      of environmental stress during prepubertal life in rats with inherited stress
      induced arterial hypertension (ISIAH) and normotensive Wistar rats on blood
      pressure (BP) levels and anxiety-related behavior. Two models of chronic stress
      (21-32 postnatal days) were used: repeated handling (HS) and unpredictable stress
      (US) of daily exposures to a variety of mild physical or psychoemotional
      stressors. Rats were tested just after the end of the chronic stress period and
      then at the age of 4 months. Chronic prepubertal stress did not affect the basal
      or stress-induced BP levels in young or adult Wistar rats. In ISIAH rats, chronic
      stress during the early phase of hypertension development did not accelerate its
      formation and did not augment its manifestation in adults. Moreover, the basal BP
      was decreased in young and adult ISIAH rats exposed to HS or US as compared to
      the age-matched controls. No long-lasting effect on BP elevation under acute
      stress in adults was found. Plasma corticosterone levels at resting and acute
      stress conditions were not changed in adult rats that had experienced prepubertal
      stress. Hypertensive rats proved to be less anxious in the elevated plus-maze
      test. The immediate effects of chronic stress were similar in the two rat
      strains: HS had an anxiolytic action while US stimulated anxiety. Long-lasting
      consequences depended on the rat strain: the anxiolytic effect of HS was retained
      in Wistar rats and US caused a greater anxiety in adult ISIAH rats. The data do
      not evidence that symptoms of anxiety are related to the development and
      maintenance of stress-sensitive arterial hypertension in ISIAH rats.

PMID- 11965353
TI  - Tyrosine hydroxylase- and/or aromatic L-amino acid decarboxylase-expressing
      neurons in the rat arcuate nucleus: ontogenesis and functional significance.
AB  - This study has evaluated in vivo, ex vivo and in vitro the ontogenesis and
      functional significance of the neurons of the arcuate nucleus (AN) expressing
      either individual enzymes of dopamine (DA) synthesis, tyrosine hydroxylase (TH)
      or aromatic L-amino acid decarboxylase (AADC) as well as both of them in rats
      from the 17th embryonic day (E) till adulthood. Immunocytochemistry, image
      analysis, confocal microscopy, high performance liquid chromatography with
      electrochemical detection and radioimmunoassay were used to solve this problem.
      Monoenzymatic TH-containing neurons were initially observed on E18 located in the
      ventrolateral AN whereas the neurons expressing only AADC or both AADC and TH
      first appeared on E20 in the dorsomedial AN. On E21, the monoenzymatic TH- or
      AADC-expressing neurons comprised more than 99% of the whole neuron population
      expressing the DA-synthesizing enzymes. In spite of an extremely small number
      (<1%) of the neurons expressing both enzymes (DArgic neurons), the dissected AN
      (ex vivo) and its primary cell culture (in vitro) contained a surprisingly high
      amount of DA and L-dihydroxyphenylalanine (L-DOPA) which were released in
      response to membrane depolarization. Furthermore, DA production in the AN of
      fetuses occurred to be sufficient to provide an inhibitory control of prolactin
      secretion, as in adults. The above data suggest that DA could be synthesized, at
      least in the AN of fetuses, by monoenzymatic neurons containing either TH or
      AADC, in co-operation. This hypothesis may be extended to adult animals as their
      AN contained the same populations of the neurons expressing DA-synthesizing
      enzymes as in fetuses though the proportion of true DArgic neurons increased up
      to 38%. During ontogenesis, the monoenzymatic TH- and AADC-containing neurons
      established axosomatic and axo-axonal junctions that might facilitate the L-DOPA
      transport from the former to the latter. Moreover, the monoenzymatic AADC
      expressing neurons project their axons to the median eminence, thereby, providing
      the pathway for the DA transport toward the hypophysial portal circulation. Thus,
      DA appears to be synthesized in the AN not only by DArgic neurons but also by
      monoenzymatic TH- and AADC-expressing neurons in co-operation.

PMID- 11965355
TI  - Molecular genetic approaches to investigate individual variations in behavioral
      and neuroendocrine stress responses.
AB  - A large response range can be observed in both behavioral and neuroendocrine
      responses to environmental challenges. This variation can arise from central
      mechanisms such as those involved in the shaping of general response tendencies
      (temperaments) or involves only one or the other output system (behavioral vs.
      endocrine response). The participation of genetic factors in this variability is
      demonstrated by family and twin studies in humans, the comparison of inbred
      strains and selection experiments in animals. Those inbred strains diverging for
      specific traits of stress reactivity are invaluable tools for the study of the
      molecular bases of this genetic variability. Until recently, it was only possible
      to study biological differences between contrasting strains, such as
      neurotransmitter pathways in the brain or hormone receptor properties, in order
      to suggest structural differences in candidate genes. The increase of the power
      of molecular biology tools allows the systematic screening of significant genes
      for the search of molecular variants. More recently, it was possible to search
      for genes without any preliminary functional hypothesis (mRNA differential
      expression, nucleic acid arrays, QTL search). The approach known as quantitative
      trait loci (QTL) analysis is based on the association between polymorphic
      anonymous markers and the phenotypical value of the trait under study in a
      segregating population (such as F2 or backcross). It allows the location of
      chromosomal regions involved in trait variability and ultimately the
      identification of the mutated gene(s). Therefore, in a first step, those studies
      skip the 'black box' of intermediate mechanisms, but the knowledge of the gene(s)
      responsible for trait variability will point out to the pathway responsible for
      the phenotypical differences. Since variations in stress-related responses may be
      related to numerous pathological conditions such as behavioral and mood
      disorders, drug abuse, cardiovascular diseases or obesity, and production traits
      in farm animals, these studies can be expected to bring significant knowledge for
      new therapeutic approaches in humans and improved efficiency of selection in farm
      animals.

PMID- 11965356
TI  - Effects of testosterone on alpha2A-adrenergic receptor expression in the rat
      brain.
AB  - Androgens are involved in regulation of behaviour through intracellular
      mechanisms owing to their receptors. Involvement of intercellular messengers such
      as brain norepinephrine and adrenergic receptors (ARs) is seemed to be necessary
      to realise hormone-dependent behavioural effects. Castration of adult male rats,
      which decreases copulatory activity in the animals, was accompanied by a
      significant increase in 3H-clonidine (alpha2-AR agonist) binding site density in
      the frontal cortex. The levels of mRNA for the alpha2A-ARs (measured by RT-PCR)
      were increased in the brainstem of castrated males in parallel to the changes in
      cortical ARs densities. Testosterone treatment, that activates copulatory
      behaviour in castrates, down regulated alpha2A-AR mRNA levels in the brainstem
      and 3H-clonidine binding sites densities in the cortex, where terminals of the
      brain stem neurones are situated. Unlike in the brainstem, castration caused a
      decrease in alpha2A-AR mRNA in the cortex and testosterone up-regulated this mRNA
      in the cortical region. The data suggested that down-regulation of alpha2-ARs
      densities in the cortex that is induced by testosterone can be preferentially
      related to alpha2-ARs subpopulation which is expressed by the brainstem neurones
      and imported into the cortex by axons of these neurones.

PMID- 11965358
TI  - Behaviour, chemosignals and endocrine functions in male mice infected with tick
      borne encephalitis virus.
AB  - Odour attractiveness, social behaviour and endocrine status of male mice (outbred
      ICR strain) were examined 6-7 days after inoculation with subclinical dose of
      tick-borne encephalitis virus (TBE). According to RT-PCR control of efficiency of
      infection, males injected with TBE were divided on the two subgroups: TBE+ (males
      with viral RNA) and TBE- (males without viral RNA). Susceptible males (TBE+
      subgroup) showed the higher level of plasma testosterone in comparison with both
      control and nonsusceptible (TBE- subgroup) males. TBE+ males had also more odour
      attraction for oestrus females and more aggressiveness in social conflict. Higher
      sexual attractiveness and aggressiveness of the infected host benefit the
      pathogen's distribution in the host population.

PMID- 11965359
TI  - Involvement of the 5-HT(1A) and 5-HT(1B) serotonergic receptor subtypes in sexual
      arousal in male mice.
AB  - The presence of a sexually receptive female behind a partition that prevents
      physical contact, but not seeing or smelling, increases blood testosterone level
      and induces the specific behavior in CBA male mice so that they more frequently
      approach the partition and spend more time near it in an attempt to make their
      way to the female. Treatment with the selective 5-HT(1A) serotonin receptor
      agonist 8-OH-DPAT (0.1, 0.25, 0.5 and 2.0 mg/kg) induced a dose-dependent
      decrease in the amount of time spent by the males near the partition, or
      "partition time", which is considered the main pattern of sexual motivation. The
      activating effect of female exposure on the male's pituitary-testicular system
      was totally blocked, as no increase in plasma testosterone level was observed.
      The 5-HT(1A) antagonist p-MPPI (0.1, 0.2 and 0.4 mg/kg) itself did not affect
      behavior or alter plasma testosterone, but attenuated the inhibiting effect of 8
      OH-DPAT on behavior and totally antagonised the effect of the 5-HT(1A) agonist on
      testosterone response. The 5-HT(1B) agonist CGS-12066A (1.0 and 2.0 mg/kg) has no
      influence on the plasma testosterone increase exhibited by the male in response
      to female exposure. At the same time, either dose of CGS-12066A significantly
      reduced the partition time. The conclusion was made that the 5-HT(1A) subtype is
      involved in controlling both behavioral and hormonal indices of sexual arousal in
      male mice, while the 5-HT(1B) receptors antagonise sexual motivation, but do not
      modify the hypothalamic-pituitary-testicular response.

PMID- 11965357
TI  - Effects of antisense oligodeoxynucleotide to the alpha2A-adrenoceptors on the
      plasma corticosterone level and on elevated plus-maze behavior in rats.
AB  - Antisense strategy was used to investigate the role of alpha2A-adrenoceptor
      (alpha2A-AR) subtype in anxiety-related behavior. A 18-mer phosphorothioate
      oligodeoxynucleotide (AS-ODN) complementary to the alpha2A-AR mRNA was
      administered to the adult male rats for 3 days (1 nmol/5 microl/day) into the
      region of locus coeruleus (LC). Control groups received infusions of either
      oligodeoxynucleotide of a random sequence (RS-ODN) or saline. Treatment with AS
      ODN significantly reduced the levels of alpha2A-AR mRNA in the brain stem. At the
      same time, AS-ODN treatment caused only a small reduction in [(3)H]clonidine
      binding (by 26-32%) in the brain stem which was not significant. Compared to both
      RS-ODN and saline controls, treatment with AS-ODN significantly increased the
      percentage of open arm entries in the elevated plus-maze while the total number
      of arm entries was unaltered. Also, AS-ODN treatment elevated basal levels of
      plasma corticosterone by 217% and 96% compared to both RS-ODN and saline
      controls. These changes in the hormone concentrations were at a level of marginal
      significance (p<0.1 versus random group). Taken together, the data indicate that
      administration of AS-ODN against alpha2A-ARs in the LC significantly reduced
      expression of alpha2A-AR mRNA in brain stem, moderately increased plasma
      corticosterone and had anxiolytic-like effect in the elevated plus-maze.

PMID- 11965360
TI  - Stress increases gene expression of phenylethanolamine N-methyltransferase in
      spleen of rats via pituitary-adrenocortical mechanism.
AB  - Gene expression of phenylethanolamine N-methyltransferase (PNMT), the enzyme
      catalyzing conversion of norepinephrine to epinephrine, has been detected in rat
      spleen using the reverse transcription polymerase chain reaction. PNMT identity
      was subsequently verified by Southern blots. Localization of the spleen cells
      responsible for the PNMT gene expression was investigated by the in situ
      hybridization and PNMT mRNA was found to be present in the white pulp. The
      hypothesis that stress may produce an increase in PNMT gene expression in rat
      spleen was tested and a robust rise in the relative abundance of PNMT mRNA levels
      was observed after a single or repeated immobilization (about 80%). Adrenalectomy
      or hypophysectomy completely prevented the immobilization-induced increase in
      spleen PNMT mRNA levels, suggesting that stress-induced PNMT gene expression in
      the spleen is regulated predominantly via pituitary-adrenocortical axis. In
      control animals, however, spleen PNMT was not significantly affected by the
      ectomies and therefore basal PNMT gene expression might be regulated by different
      mechanism(s).Thus, PNMT gene expression in the rat spleen is exaggerated by
      stress stimuli, suggesting its role in physiological regulations.

PMID- 11965361
TI  - Synthesis of a molecular mimic of the Glc1Man9 oligoside as potential inhibitor
      of calnexin binding to DeltaF508 CFTR protein.
AB  - Deletion of phenylalanine at position 508 of the CFTR protein is associated with
      a severe form of cystic fibrosis. Biosynthetic arrest of the misfolded DeltaF508
      CFTR protein in the endoplasmic reticulum is due to prolonged interaction with
      protein chaperones. In order to overcome this retention and thereby restore the
      delivery of the protein to the plasma membrane, a molecular mimic of the
      glycoprotein oligoside moiety has been designed and synthesized. Ability of this
      mimic to inhibit the binding of the natural Glc1Man9GlcNAc oligoside to calnexin
      has been measured.

PMID- 11965362
TI  - Novel camptothecin derivatives. Part 1: oxyalkanoic acid esters of camptothecin
      and their in vitro and in vivo antitumor activity.
AB  - A series of oxyalkanoic acid esters of (20S)-camptothecin derivatives was
      prepared by the method of acylation. Their antitumor activity was evaluated on
      cancer cells in vitro by the colony formation assay and in vivo. These newly
      synthesized derivatives show a dramatically higher chemotherapeutic activity in
      killing human cancer cells than the parent drug, camptothecin, and clinically
      available drugs, irinotecan and taxol.

PMID- 11965363
TI  - Structure-activity relationships for mini atrial natriuretic peptide by proline
      scanning mutagenesis and shortening of peptide backbone.
AB  - MiniANP is a synthetic pentadecapeptide analogue of atrial natriuretic
      polypeptide (ANP). We have used the proline-scanning mutagenesis and the analogue
      peptides with shorter backbones to characterize the turn-like conformation at
      residue 6-9 and an extended structure of Gly5-Gly6 as the receptor-bound
      structure of miniANP. A docking study of miniANP at the binding site of the type
      A natriuretic peptide receptor (NPR-A) supported the deduced conformation in the
      receptor-bound structure.

PMID- 11965364
TI  - Enantioselective synthesis of S-(+)-2beta-carboalkoxy-3alpha-[bis(4
      fluorophenyl)methoxy]tropanes as novel probes for the dopamine transporter.
AB  - Synthesis of a series of pure S-(+)-2beta-carboalkoxy-3alpha-[bis(4
      fluorophenyl)methoxy]tropanes (>99% ee) was achieved by employing a chiral amine
      induced asymmetric reaction of tropinone with methyl cyanoformate as the key
      step. In this series, all of the S-(+)-enantiomers were 2-fold more potent than
      their racemic mixtures and all displayed high-affinity binding for DAT (K(i)=13
      40 nM). These data support previous findings of significant divergence in
      structural requirements for high-affinity DAT binding among tropane-based
      inhibitors. Furthermore, the 2-substituent in the 3alpha-[bis(4
      fluorophenyl)methoxy]tropane series is well tolerated at the DAT but not at SERT
      (K(i)=690-2040 nM), or muscarinic M(1) receptors (K(i)=133-4380 nM) resulting in
      highly selective DAT ligands that may provide new leads toward a cocaine-abuse
      therapeutic.

PMID- 11965365
TI  - Synthesis, photobiological activity and photoreactivity of methyl-thieno-8
      azacoumarins, novel bioisosters of psoralen.
AB  - 4,4'-dimethyl-thieno-8-azacoumarin (6) and 4,4',5'-trimethyl-thieno-8-azacoumarin
      (8) were synthesised. Their photobiological activity was tested on human tumour
      cell lines. Interestingly, for 6, a photocytotoxic ability higher in HL-60,
      comparable in HeLa cells, with respect to that of the well-known drug 8
      methoxypsoralen (8-MOP), was demonstrated. The covalent photoaddition to DNA
      occurs by means of the molecular mechanism already demonstrated for
      furocoumarins. However, it is noteworthy that no skin phototoxicity appears.

PMID- 11965366
TI  - Synthesis of aminoglycoside-DNA conjugates.
AB  - Development of aminoglycoside-nucleic acid conjugates is presented. Synthesis of
      a DNA dimer covalently linked to kanamycin and neomycin isothiocyanates has been
      carried out. The development of such conjugates will help couple the sequence
      specificity of nucleic acids to the electrostatic/shape complementarity of
      aminoglycoside antibiotics in binding nucleic acid targets.

PMID- 11965367
TI  - Induction of apoptosis by aryl-substituted diamines: role of aromatic group
      substituents and distance between nitrogens.
AB  - A series of aromatic substituted diamines was synthesized and characterized for
      their cytotoxic profiles against human breast and prostate tumor cell lines.
      Following a structure function analysis of the effects of changes of the benzyl
      substituents and the distance between amino groups the most potent analogues were
      analyzed biologically and were shown to induce apoptosis. These compounds do not
      induce the enzyme SSAT or deplete intracellular polyamine levels, mechanisms
      demonstrated by other cytotoxic polyamine analogues.

PMID- 11965368
TI  - Potent inhibitors of farnesyltransferase and geranylgeranyltransferase-I.
AB  - Compound 1 has been shown to be a dual prenylation inhibitor with FPTase (IC50=2
      nM) and GGPTase-I (IC50=95 nM). Analogues of 1, which replaced the cyanophenyl
      group with various biaryls, led to the discovery of highly potent dual
      FPTase/GGPTase-I inhibitors. 4-trifluoromethylphenyl, trifluoropentynyl, and
      trifluoropentyl were identified as good p-cyano replacements.

PMID- 11965370
TI  - The mechanism of the irreversible inhibition of estrone sulfatase (ES) through
      the consideration of a range of methane- and amino-sulfonate-based compounds.
AB  - We report the results of our study into a series of simple phenyl and alkyl
      sulfamates and alkyl methanesulfonates as potential inhibitors of the enzyme
      estrone sulfatase (ES). The results of the study show that the substituted phenyl
      sulfamates are good irreversible inhibitors; the alkyl sulfamate compounds were
      found to lack inhibitory activity; whilst the large alkyl chain containing
      methanesulfonate-based compounds were found to possess weak reversible inhibitory
      activity. Using the results of the inhibition study, we postulate the probable
      mechanism for ES and suggest that an attack by the gem-diol is a major
      requirement prior to the hydrolysis of the sulfamate group, following which,
      attack on the active site C=O occurs and which therefore leads to the production
      of an imine type functionality, resulting in irreversible inhibition.

PMID- 11965371
TI  - Synthesis of a novel fluorescent probe for estrogen receptor.
AB  - A novel estradiol-mimetic fluorescent probe 5 was synthesized from
      diethylstilbestrol (DES, 1), which is useful for probing estrogen receptor
      (ERalpha), a prognostic indicator of estrogen-dependent cancers, and for
      developing a homogeneous fluorescence polarization (FP) assay to identify the
      ligands of estrogen receptor.

PMID- 11965369
TI  - Design, synthesis and biological activity of novel non-peptidyl endothelin
      converting enzyme inhibitors, 1-phenyl-tetrazole-formazan analogues.
AB  - A novel non-peptidyl endothelin converting enzyme inhibitor was obtained through
      a pharmacophore analysis of known inhibitors and three-dimensional structure
      database search. Analogues of the new inhibitor were designed using the structure
      activity relationship of known inhibitors and synthesized. In anesthetized rats,
      intraperitoneal administration of the analogues suppressed the pressor responses
      induced by big endothelin-1.

PMID- 11965372
TI  - Imidazole-based ligands of the Src SH2 protein.
AB  - Starting from known Src SH2 inhibitors incorporating five-membered heterocycles
      or benzamide scaffolds, we prepared tetrasubstituted imidazole compounds able to
      interact with the pY, pY+1 and pY+3 binding sites of the Src SH2 protein. The
      synthesis and biological data are presented.

PMID- 11965373
TI  - Discovery of highly potent Src SH2 binders: structure-activity studies and X-ray
      structures.
AB  - Optimization of the hydrophobic moiety of caprolactam/thiazepinone based
      compounds led to the identification of potent Src SH2 binders in two different
      series incorporating a phosphotyrosine group (RU 81843) or a phosphobenzoic group
      (RU 79181). The X-ray co-structures with the Src SH2 domain revealed different
      binding modes for RU 81843 and RU 79181, and an excellent fit between RU81843 and
      the Src SH2 protein thus explaining its high potency (9 nM, 15-fold more potent
      than pYEEI reference peptide).

PMID- 11965374
TI  - Small ligands interacting with the phosphotyrosine binding pocket of the Src SH2
      protein.
AB  - Various small fragments bearing phosphate, phosphonate or phosphonic acid
      moieties have been prepared through parallel synthesis and their binding
      potencies evaluated on the Src SH2 protein using a BIAcore assay. This provided
      us insight into the requirement of the Src SH2 pTyr binding pocket and some
      promising small ligands have been characterised.

PMID- 11965375
TI  - Comparative study of transfection efficiency of cationic cholesterols mediated by
      liposomes-based gene delivery.
AB  - To develop the efficient non-viral vector for gene delivery, we compared
      transfection activities of cationic cholesterol derivatives. We found that the
      stability of the liposome-DNA complex in the presence of endosome deeply related
      to the transfection efficiency. We also found that the introduction of a
      hydrophilic group to the amino terminal of the cholesterol derivative decreased
      stability and facilitated the release of DNA from the endosome, resulting in
      higher transfection efficiency.

PMID- 11965376
TI  - Optimization of the 4-aryl group of 4-aryl-pyridine glucagon antagonists:
      development of an efficient, alternative synthesis.
AB  - A narrow structure-activity relationship was established for the 4-aryl group in
      4-aryl-pyridine glucagon antagonists, with only small substituents being well
      tolerated, and only at the 3'- and 4'-positions. However, substitution with a 2'
      hydroxy group gave a ca. 3-fold increase in activity (e.g., 4'-fluoro-2'-hydroxy
      analogue 33, IC50=190 nM). For efficient preparation of 2'-substituted
      phenylpyridines, a novel synthesis via pyrones and 4-methoxy-pyridines was
      developed.

PMID- 11965377
TI  - Design and synthesis of aminophenol-based factor Xa inhibitors.
AB  - A novel potent and selective aminophenol scaffold for fXa inhibitors was
      developed from a previously reported benzimidazole-based naphthylamidine
      template. The aminophenol template is more synthetically accessible than the
      benzimidazole template, which simplified the introduction of carboxylic acid
      groups. Substitution of a propenyl-para-hydroxy-benzamidine group on the
      aminophenol template produced selective, sub-nanomolar fXa inhibitors. The
      potency of the inhibitors is partially explained with the aid of a trypsin
      complex crystal structure.

PMID- 11965378
TI  - Benzimidazole-based fXa inhibitors with improved thrombin and trypsin
      selectivity.
AB  - Optimization of the benzimidazole-based fXa inhibitors for selectivity versus
      thrombin and trypsin was achieved by substitution on the benzimidazole ring and
      replacement of the naphthylamidine group. Substitution of a nitro group at the 4
      position on the benzimidazole improves both potency against fXa and selectivity
      versus thrombin. Alternatively, replacement of the naphthylamidine with either a
      biphenylamidine or propenylbenzamidine not only improves fXa potency and
      selectivity versus thrombin, but selectivity versus trypsin as well.

PMID- 11965379
TI  - Enantiospecific, selective cyclooxygenase-2 inhibitors.
AB  - Cyclooxygenase inhibition studies with novel indomethacin alkanolamides
      demonstrate the potential for dramatic differences in inhibitor properties
      conferred by subtle structural modifications. The transformation of non-selective
      alpha-(S)-substituted indomethacin ethanolamides to potent, COX-2 selective
      inhibitors by simple stereocenter inversion highlights this property.

PMID- 11965380
TI  - Synthesis and evaluation of vancomycin and vancomycin aglycon analogues that bear
      modifications in the residue 3 asparagine.
AB  - The synthesis and biological evaluation of a set of residue 3 analogues of
      vancomycin and its aglycon are described. These investigations follow from the
      promising biological activity of a protected and synthetically modified
      vancomycin aglycon analogue in which the asparagine side chain was modified to
      possess a nitrile, rather than a carboxamide. Although this modification
      typically was detrimental to antimicrobial activity, hydrophobic vancomycin
      aglycon analogues that lack a lipid anchor as well as the disaccharide are
      detailed that exhibit unusual potency against VanB, but not VanA, resistant
      bacteria.

PMID- 11965381
TI  - Novel diamide-based inhibitors of IMPDH.
AB  - A series of novel amide-based small molecule inhibitors of inosine monophosphate
      dehydrogenase is described. The synthesis and the structure-activity
      relationships (SARs) derived from in vitro studies are presented.

PMID- 11965383
TI  - Ready, aim, fire: the art of biotech publicity.

PMID- 11965384
TI  - New insights into Alzheimer's disease.

PMID- 11965385
TI  - Vaccine against hospital-acquired Staphylococcus aureus.

PMID- 11965386
TI  - Caspase inhibitors for liver disease.

PMID- 11965390
TI  - Instruments in verse.

PMID- 11965391
TI  - Stem cells: hype or hope?

PMID- 11965392
TI  - Osteoprotegerin and bone loss associated with spaceflight.

PMID- 11965393
TI  - Chip, chip, array! Three chips for post-genomic research.

PMID- 11965395
TI  - Transgenic systems in drug discovery: from target identification to humanized
      mice.
AB  - Pharmaceutical companies are faced with the challenge that only approximately 10%
      of compounds tested in costly clinical trials eventually become a new drug.
      Investment in early discovery research can decrease this attrition in late-stage
      R&D and focus resources on the best targets. Transgenic technology influences
      decision-making in target identification, target validation, and can also provide
      better models for human diseases, as well as models designed to alert researchers
      early about potential issues with drug metabolism and toxicity. Here we review
      how transgenic technology can reduce the late-stage attrition by increasing the
      quality of both the target and the compound.

PMID- 11965396
TI  - Structure-based screening and design in drug discovery.
AB  - Structure-based screening represents an integrated approach for the
      identification and optimization of hits by the combined use of nuclear magnetic
      resonance (NMR) spectroscopy, homology modeling and X-ray crystallography. A
      general feature of the methodology is the introduction of structure-based methods
      (NMR, modeling and X-ray) early in the drug discovery process to optimize hits in
      terms of their affinities and specificities. This approach promises to deliver
      leads with improved physicochemical properties as compared with leads generated
      from a traditional HTS program. This review presents examples of structure-based
      screening from published and in-house drug discovery projects.

PMID- 11965397
TI  - Targeting tumors with non-viral gene delivery systems.
AB  - Targeting therapeutic genes to tumors is an attractive concept in curing
      malignant diseases. Systemic gene delivery systems are needed for therapeutic
      applications in which the target cells are not directly accessible, and which can
      only be reached via the systemic route. Recent developments in the field of non
      viral gene delivery have shown that, based on (poly)cationic carrier molecules,
      DNA can be efficiently targeted to tumors via the bloodstream. Tailor-made
      synthetic vectors can be used to achieve predominant gene expression in tumor
      tissue. Therapeutic concepts based, for example, on suicide genes or cytokines,
      showed encouraging results in preclinical and also in first clinical evaluations.

PMID- 11965399
TI  - NTP Renal Toxicity Studies of Selected Halogenated Ethanes Administered by Gavage
      to F344/N Rats.
AB  - The National Cancer Institute and National Toxicology Program have performed 2
      year toxicology and carcinogenesis studies with a number of ethanes substituted
      with chlorine or bromine. A review of the results of studies with these
      halogenated ethanes has revealed several consistencies between the pattern of
      halogen substitution and neoplastic responses in some affected organs. One of
      these consistencies was the finding of a modest increase in the incidence of
      renal tubule cell neoplasms in male rats administered penta- or hexachloroethane.
      Certain aspects of the nephropathy also noted in these studies resembled what is
      now recognized as a distinct hyaline droplet nephropathy typically associated
      with the accumulation of alpha[alpha]2&mgr;-globulin in renal tubule cells. In an
      attempt to determine some of the structure activity relationships involved in the
      induction of hyaline droplet nephropathy by halogenated ethanes, a series of
      commercially available ethanes substituted with three or more chlorines, four or
      more bromines, or a combination of chlorines and fluorines was studied in a short
      term renal toxicity assessment in male F344/N rats. All chemicals were
      administered by gavage in corn oil to groups of five male rats once daily for 21
      days. The doses selected for study, 0.62 and 1.24 mmol/kg per day, were based on
      those used in the 2-year pentachloroethane studies. The following chemicals were
      evaluated: 1,1,1,2- and 1,1,2,2-tetrachloroethane; pentachloroethane; 1,1,2,2
      tetrachloro1,2-difluoroethane; 1,1,1-trichloro-2,2,2-trifluoroethane; 1,2
      dichloro-1,1-difluoroethane; 1,1,1-trichloroethane; hexachloroethane; 1,1,1,2-and
      1,1,2,2-tetrabromoethane; and pentabromoethane. Evaluations included survival,
      mean body weight gains, clinical signs, organ weights, urinalysis, and
      histopathologic examination of the right kidney and liver. The kidneys of rats
      that showed a difference in renal protein droplet accumulation compared to the
      controls were evaluated for replicative DNA synthesis by staining for
      proliferating cell nuclear antigen. For most groups, survival was not affected by
      chemical treatment; however, all rats administered either dose of 1,1,2,2
      tetrabromoethane died by Day 11, and all rats administered 1.24 mmol/kg
      pentabromoethane, 1,1,1,2-tetrabromoethane, or 1,1,2,2-tetrachloroethane died
      before the end of the study. Rats receiving 0.62 mmol/kg pentabromoethane gained
      less weight than the controls, and rats in the 0.62 mmol/kg 1,1,1,2
      tetrabromoethane group lost weight during the study. Increased kidney weights and
      signs of renal toxicity, indicated by urinalysis results, were noted in rats in
      many of the groups administered halogenated ethanes, but these observations were
      not always coincident with a diagnosis of hyaline droplet nephropathy. Hyaline
      droplet nephropathy was observed only in rats receiving penta-, hexa-, or 1,1,1,2
      tetrachloroethane. The renal tubule cell labeling index was increased, indicating
      replicative DNA synthesis, in male rats receiving chemicals that induced hyaline
      droplet nephropathy as well as in males receiving pentabromoethane or 1,1,2,2
      tetrachloroethane and in female negative control rats administered
      pentachloroethane; thus some of the halogenated ethanes appeared to cause
      significant renal toxicity not associated with hyaline droplet nephropathy. In
      summary, of the halogenated ethanes studied, the capacity to induce hyaline
      droplet nephropathy in male rats was restricted to ethanes containing four or
      more halogens, and only the chlorinated ethanes were active. If the ability to
      induce hyaline droplet nephropathy is the determining factor in the induction of
      renal tubule cell neoplasms by halogenated ethanes, then an absence of kidney
      neoplasms in male rats would be predicted in the event that 2-year studies were
      performed with the bromo- or chlorofluoroethanes.

PMID- 11965400
TI  - Interrelationship between radiologic findings and prognosis of epilepsy in
      children with neurocysticercosis.
AB  - INTRODUCTION: Epileptic manifestations of Neurocysticercosis (NC) appear to
      depend on number and localization of the cysts. The objective of this study was
      to investigate the relationship between CT findings, number of parasites and the
      evolutive stage of the cysts, and the prognosis of epilepsy in children with NC.
      METHOD: We studied 28 patients with the parenchymal form of NC, considering:
      epilepsy duration; seizure frequency before and after AED treatment; seizure
      control; number of AED and recurrence after AED withdrawal. Clinical information
      was crossed with the number of lesions and disease activity in univariate
      comparison. RESULTS: The analysis of the clinical data in relation to the number
      of lesions and disease activity showed no statistical difference among the
      variables (p>0.05). CONCLUSION: We conclude that the course of epilepsy due to NC
      in childhood cannot be based exclusively on the number or stage of the parasites.

PMID- 11965401
TI  - Daytime sleepiness and academic performance in medical students.
AB  - This report presents an analysis of the complaints of increasing daytime
      sleepiness as well as a study on their possible effects on the academic
      performance of medical students at the University of Brasilia. The Epworth
      Sleepiness Scale was applied to 172 medical students, at the beginning of August
      1997 and at the end of November 1997. Academic performance was measured by
      analyzing the number of SS grades (from 9.0 to 10 over ten) and MM grades (from
      5.0 to 6.9) attained in exams at the end of that school period. The results
      showed that at the beginning of the semester, 68 (39.53%) of these 172 students
      already presented with excessive daytime sleepiness, and that of the 104
      remaining students, 38 (22%) developed daytime sleepiness by the end of the
      semester. Furthermore, it was observed that the sleepier students did not achieve
      as well as the others on their final examinations.

PMID- 11965402
TI  - Preservation of the olfactory tract in bifrontal craniotomy.
AB  - The bifrontal craniotomy approach used to be associated with a high percentage of
      olfactory tract damage. We present our experience with this technique, that was
      used with excellent results in a series of 11 patients that underwent the
      surgical approach described in this paper. We support the idea that bilateral
      subfrontal craniotomy allows a wide operative exposure as well as the complete
      anatomic and functional preservation of the olfactory tracts bilaterally.

PMID- 11965403
TI  - Movement disorders induced by peripheral trauma.
AB  - Movement disorders induced by central nervous system trauma are well recognized.
      However, over the last few years, attention has been drawn to the role of
      peripherally induced movement disorders. We describe three patients presenting
      respectively dystonia, tremor and choreoathetosis associated with tremor and
      dystonia of the body parts previously exposed to traumatic injuries.
      Pathophysiological mechanisms underlying these phenomena are not entirely known,
      but functional changes in afferent neuronal input to the spinal cord and
      secondary affection of higher brain stem and subcortical centers are probably
      involved.

PMID- 11965404
TI  - Cognitive rehabilitation of naming deficits following viral meningo-encephalitis.
AB  - OBJECTIVE: This case study describes the neuropsychological assessment and
      cognitive rehabilitation of a patient who developed word retrieval deficits for
      objects and people's names, following an episode of viral meningo-encephalitits.
      It shows the implementation and outcome of two techniques adapted to the
      patient's individual characteristics and context providing a more ecologically
      valid approach. METHODS: In the first technique, "verbal semantic association",
      the patient was required to describe what she knew about an object as a strategy
      to help her retrieve its name. In the second one, "face-name association" she was
      taught to apply a visual-imagery technique in order to retrieve relevant people's
      names. RESULTS: Following the implementation of these procedures there was a
      decrease in the number of episodes of failure to retrieve objects and people's
      names in her everyday life context. CONCLUSION: The improvement found in the
      patient's ability to retrieve words is discussed in terms of the utility of
      cognitive rehabilitation programmes and cognitive models of language processing

PMID- 11965405
TI  - Neuropsychological, neuroimage and psychiatric aspects of primary Sjogren's
      syndrome.
AB  - We report a case of a 49-year-old woman diagnosed with primary Sjogrens Syndrome
      (pSS) who was submitted to extensive neuropsychobiological assessment.
      Examination revealed a Wechsler Adult Intelligence Scale-Revised (WAIS-R) Full
      Scale IQ of 97 with no Verbal/Performance IQ discrepancy and performance below
      estimated premorbid levels on arithmetic skills, visual tracking, naming and
      delayed paired associate learning/memory. CT scans of the brain were normal.
      However, there were subcortical hyperintensities on MRI and left parieto-temporal
      hypoperfusion on SPECT. Neuropsychological impairment is consistent with the
      pattern of neuroimage findings. We hypothesize that the pathophysiological
      mechanisms of pSS involve direct immune attack on neurons in addition to indirect
      effects through small-vessel angiopathy and thereby induce natural fracture lines
      in behavior according to location in the central nervous system.

PMID- 11965406
TI  - Terminal ileum submucous plexus: Study of the VIP-ergic neurons of diabetic rats
      treated with ascorbic acid.
AB  - The aim of this study was to evaluate the effect of the ascorbic acid (AA)
      supplementation on the neurons that produce the vasoactive intestinal peptide
      (VIP) in the submucous plexus of the ileum of rat, four months after the
      induction of experimental diabetes mellitus with streptozotocin. Three groups of
      rats were used: C - control, D - diabetic, DA - diabetic receiving AA. We have
      measured the immunoreactivity and area of 80 cellular bodies of VIP-ergic neurons
      from each studied group. In the diabetic animals, we have observed hyperphagia,
      polydipsia, and an increase of glycemia and glycated hemoglobin. The VIP-ergic
      neurons have presented an increase of their immunoreactivity and the highest
      profiles when compared to the other groups. In the diabetic animals supplemented
      with AA it has been observed a small reduction in the glycemia and the water and
      food intake. We have also noticed smaller immunoreactivity in their VIP-ergic
      neurons, similar to what we have observed in the control group animals (group C).

PMID- 11965407
TI  - [Buspirone increases D2-like dopaminergic receptor density in rat corpus
      striatum].
AB  - Buspirone (busp) a piperazinyl derivative with anxiolytic properties is a partial
      agonist on 5-HT1A with affinity for D2-like dopaminergic receptors (RD2). The
      objective of this study was to verify the effects of busp on RD2. Female Wistar
      rats 150-200 g were treated with busp (5 and 10 mg/kg, p.o.) 1 or 2 times daily
      for 7 days. Controls (C) received saline. The density of RD2 (fmol/mg protein)
      was determined through binding assays in striatum (ST) using [3H]-spiroperidol as
      radioligand. No alteration in Bmax or Kd values were seen after busp
      administration once a day. However, a RD2 upregulation of 55 % increase was
      observed after busp 2 times a day with no change in Kd values. The results showed
      that busp interact not only with serotonergic, but also with dopaminergic system.

PMID- 11965408
TI  - [Definition of the anterolateral occipital lobe limit in anatomical specimens and
      image examination].
AB  - The anterolateral limit of the occipital lobe was studied in anatomical specimens
      and with neuroimaging. Seven human cadaver heads, 103 normal CT-scan and 104 MRJ
      of the brain were studied. There was a fold of the dura mater on the transverse
      sinus (preoccipital tentorial plica) and a bony protuberance related directly to
      the preoccipital notch. It was also determined the mean distance between the
      parieto-occipital sulcus and the lambdoid suture. In the imaging studies,
      especially magnetic resonance, it was possible to identify the preoccipital notch
      and/or a protuberance in the cranial vault related to this notch, besides the
      parieto-occipital sulcus and lambdoid suture, making possible, therefore, the
      definition of the anterolateral limit of the occipital lobe.

PMID- 11965409
TI  - [Prevalence and pattern of distribution of cerebrovascular diseases in 242
      hospitalized elderly patients, in a general hospital, autopsied in Belo
      Horizonte, Minas Gerais, Brazil, from 1976 to 1997].
AB  - OBJECTIVE: To describe the prevalence and the types of cerebrovascular diseases
      (CVDs) in autopsied elderly individuals. METHOD: Consecutive clinical charts and
      neuropathological reports of 242 patients aged 61 years or older were reviewed.
      The patients died in Hospital das Clinicas, Federal University of Minas Gerais,
      in Belo Horizonte, Minas Gerais, Brazil, from 1976 to 1997. RESULTS: The
      prevalent diseases of the central nervous system (CNS) found in decreasing order
      were: CVDs (71.9%), infections (12.4%), neoplasms (7.1%), head trauma (3.7%),
      nutritional diseases (2.5%) and degenerative diseases (1.7%). The most common
      CVDs were cerebral atherosclerosis (61.2%), hypertensive cerebrovascular disease
      (25.6%) and cerebral infarct (14.9%). There was an increase in prevalence and
      severity of atherosclerosis and an increase in prevalence of hypertensive
      cerebrovascular disease with advancing age. A significant association between
      hypertensive cerebrovascular disease and atherosclerosis was found. The CVDs
      patients had clinical stroke and this was the direct cause of death in 42,7% and
      17,3% of the cases, respectively. CONCLUSION: The CVDs were the most prevalent
      group of diseases of the CNS in elderly patients. Atherosclerosis and
      hypertensive cerebrovascular disease were the most common CVDs, and its
      prevalence increased with advancing age. Hypertensive cerebrovascular disease was
      significantly associated with atherosclerosis.

PMID- 11965410
TI  - [The baby alarm distress scale: a validity study].
AB  - It should take into account the psychopatologic context and the child's
      development moment to evaluate the baby alarm distress from a standardized
      instrument. We present the BADS questionnaire validation by its application in 90
      children, from 0 to 2 years-old, obtaining a K=0.783 to p<0.01, with a Spearman
      coefficient of 0.866 and factorial analysis to 4 factors to 63.5% of the
      population studied. With these psychometrical qualities, the scale shows its
      importance as a screening but is important its study in others populations.

PMID- 11965411
TI  - [Prevalence of dementia in several regions of the world: analysis of
      epidemiologic studies from 1994 to 2000].
AB  - OBJECTIVE: To analyse the prevalence studies of dementia from 1994 to 2000.
      METHODS: The papers were searched on Medline and Lilacs and the inclusion
      criteria were: to be an original study, that estimated dementia prevalence and
      investigated community samples. RESULTS: thirty-eight studies were evaluated from
      all continents. The mean age-specific prevalence rates of dementia were 1,17% for
      the 65-69 years group, and 54,83% over 95 years. The results were strongly
      influenced by age. Dementia prevalence rates were higher on women on 75% of the
      papers reviewed. The Alzheimer's disease/vascular dementia ratio was higher in
      South America and lower in Asia. DISCUSSION: Methodological advances were found,
      specially regarding the homogeneity of diagnostic criteria. The effect of age on
      the rates of dementia prevalence was pronounced, up to 90 years of age.

PMID- 11965412
TI  - [Cognitive rehabilitation in Alzheimer's disease patients: multidisciplinary team
      report].
AB  - OBJECTIVE: This study aims to show preliminary results of the 'combined
      treatment' (acetylcholinesterase inhibitor + cognitive training) on a group of
      mild Alzheimer's disease (AD) patients, followed-up for 7 months. METHODS: Six
      mild AD patients, diagnosed according to ICD-10 and NINCDS-ADRDA criteria, were
      included on a open trial with Rivastigmine, 6-12 mg/day, for 2 months, followed
      by a weekly cognitive rehabilitation group, for 5 months. Caregivers were
      submitted to a weekly group of counseling and support for 5 months. RESULTS:
      Stabilization or mild improvement of patients' cognitive and activities of daily
      living deficits were found, besides reduction of patients and caregivers'
      depressive and anxiety levels. CONCLUSION: The 'combined treatment' can help on
      the stabilization or result on a mild improvement of AD patients' cognitive and
      functional deficits. Support and counseling interventions can reduce the levels
      of caregivers' psychiatric symptoms.

PMID- 11965413
TI  - [Prevalence of epilepsy in Bakairi indians from Mato Grosso State, Brazil].
AB  - The purpose of this cross-sectional study was to evaluate the prevalence of
      epilepsy in a population based sample: the Bakairi indians, who live on the banks
      of Paranatinga river in the central plateau of Mato Grosso state, Brazil. This
      population is composed of 483 inhabitants. The study was outlined in two stages,
      and the investigation was door-to-door in a total of 103 houses. The results of
      the instrument showed a sensitivity of 88% (CI- 95%, 84.9-93), specificity of
      97.8% (CI-95, 95-98). The prevalence of active epilepsy was 12.4 per mil, and
      inactive was 6.2 per mil. This prevalence of the epilepsy was considered high
      probably due to some familial risk factor (p=0.04) among those Indians, while
      other factors were not important.

PMID- 11965414
TI  - [Deep brain stimulation of subthalamic nucleous in Parkinson's disease].
AB  - We present the preliminary results in patients well selected to be implanted by
      deep brain stimulation (DBS) for Parkinsons's disease (PD). METHODS: 8 PD
      patients with disabled tremor, akinetic/bradikinetic and rigidity, in spite of
      best therapeutic assay with poor response were referred to surgery. It was
      implanted DBS Itrell 2. Theses patients were evaluated by the following scales:
      UPDRS, Schwab and England. RESULTS: The preliminary results in 6 months showed
      significant improvement of motor performance and it is shown by the scores. There
      were no complications so far with these procedures. CONCLUSION: The preliminary
      results indicate that DBS is highly effective, with benefit to those patients and
      it is according to literature.

PMID- 11965415
TI  - [Analysis of breathing function in Parkinson's disease].
AB  - We studied 40 parkinsonian patients (P), mean age 50-80 years, with Hoehn and
      Yahr stages I-III and 40 no parkinsonian patients (NP), with similar
      characteristics. The results of the thoracic amplitude was 1,8+/-0,8cm of P that
      showed a reduction to 4,3+/-1,0 cm of NP (p=0,00001), the vital capacity and
      forced vital capacity, 66,8+/-20,3% and 69,6+/-22,2% of P was decreased that
      82,3+/-15,7% and 82,7+/-16,6% of NP (p=0,00001 and p=0,0023). There was not
      difference among the maximal inspiratory and expiratory mouth pressures, 33,5+/
      12,7 cmH2O and 36,3+/-17,8 cmH2O of P and 37,0+/-12,2 cmH2O and 43,1+/-16,6 cmH2O
      of NP (p=0,1753 and p=0,0398), the forced expiratory volume in 1 second, 71,3+/
      25,6% of P and 80,6+/-23,6% of NP (p=0,0899), and the forced expiratory volume in
      1 second/ forced vital capacity, 104,5+/-19,9% of P and 97,4+/-22,8% of NP
      (p=0,1234). The parkinsonian patients present restrictive pulmonary dysfunction,
      low chest wall compliance and the respiratory muscle strength do not decreased.

PMID- 11965416
TI  - [Comparative study for ruptured aneurysms treated by surgery and endovascular
      method].
AB  - The management of intracranial aneurysms has truly evolved after the introduction
      of the endovascular treatment. In this paper we compare patients that were
      operated or embolized for intracranial aneurysms. Between 1995 and 1999, 78 grade
      I to III ruptured aneurysms were treated in our service: 52 patients were
      operated, 21 were embolized and 5 were submitted to combinated endovascular and
      surgical treatment. In the surgical group, clinical outcome was very good in
      80.8% of cases with 5% of mortality with 96.2% of total exclusion of the
      aneurysm. In the endovascular group, 95% of cases the clinical outcome was very
      good with only 42.8% of total exclusion of the aneurysm. By the endovascular
      method for treatment of aneurysms, we can obtain a good clinical outcome but a
      poor radiological outcome and sometimes need a complementary surgical procedure
      to treat residual aneurysm.

PMID- 11965417
TI  - [Surgery of frontal sinus osteoma].
AB  - Frontal sinus osteomas are 57% of all paranasal sinus osteomas, with an incidence
      of 00.1 to 3%. Surgical removal of the frontal sinus osteomas is done in
      symptomatic patients. Asymptomatic patients can be managed conservatively or
      submitted to surgery in spite of its location or extension. Five patients having
      the diagnosis of frontal sinus osteoma were operated on between 1995 and 1999.
      Medium age was 38.4 years (from 12 to 55 years), 3 male and 2 female. Symptoms
      occurred from 6 months to 3 years, average of 10.5 months. Four patients had
      previous headache and one had epistaxis. All patients had standard radiological
      exams and computed tomography with coronal and axial studies of paranasal sinus.
      In two patients the diameter of the osteoma was larger than 3 cm and in three
      smaller than 3 cm. The choice between coronal and supraciliar approach was made
      according to esthetics, supraciliar approach was made in only one bald patient
      even with the tumor being large and extending to ethmoidal sinus. Any intra
      operative difficulty was related to the choice of the approach. Naso-frontal
      ostium was not obstructed in intra operative course. Minimal postoperative follow
      up was of two years. Osteomas were radically removed in all patients with no
      recurrence or residual tumor. Clinical findings, radiological exams and surgical
      approaches are discussed. No postoperative complications occurred.

PMID- 11965419
TI  - [ACTH pituitary adenomas: neurosurgical aspects].
AB  - We report our experience with 19 cases of ACTH secreting pituitary adenomas. They
      were microadenomas in 50% of the cases, coming with the typical picture of the
      Cushing syndrome. The ACTH adenoma associated with other types of hormones tend
      to show visual alterations. The treatment is often surgical using the
      transsphenoidal approach. The results were satisfactory in most of the cases. For
      those in which surgical cure was not reached, radiotherapy was indicated.

PMID- 11965418
TI  - [Prolactinomas: neurosurgical aspects].
AB  - We report our experience with 38 cases of prolactin secreting pituitary adenomas.
      The adenomas were divided in three different groups. The adenomas producing only
      prolactin tend to be microadenoma and they show the typical alterations of this
      type of tumor. The GH-PRL, GH-alpha subunit, the other combinations, and the
      pluri hormonal adenomas tend to present with visual symptoms. The treatment of
      the prolactinomas is initially clinical and the surgical indication for this type
      of adenomas is related to intolerance to the medication or to visual alterations.
      Surgical result with total resection of the tumor was possible in 50% of the
      cases.

PMID- 11965420
TI  - [Nonfuntional pituitary adenomas: evaluation of 36 patients].
AB  - We present our experience with 36 cases of nonfunctional pituitary adenomas.
      These tumors were divided into non reactive and inactive in agreement with the
      immunohistochemical study. They present with visual symptoms, mainly bitemporal
      hemianopsia; they were macroadenomas, either invasive or non invasive, in both
      groups. The treatment is surgical using the transsphenoidal approach. Total
      resection was possible in about 40% of the cases. Visual improvement occurred in
      90% of the patients.

PMID- 11965421
TI  - [Growth pituitary adenomas: evaluation of 20 patients].
AB  - The growth hormone secreting pituitary adenomas can be mono, bi or pluri
      hormonals. The most frequent association of GH is with the sub unit alpha or with
      the prolactin. This type of adenoma comes with the classic alterations of
      acromegaly, but when they produce more than one hormone, visual symptoms can be
      present. The adenoma producing just GH hormone is generally microadenoma and the
      other two groups tend to be macroadenoma. We analyze 20 cases of these adenomas
      and we have found quite satisfactory surgical result for the mono-hormonal type
      group. Radiotherapy should be considered in cases of partial resection.

PMID- 11965423
TI  - [Thanatophoric dysplasia: report of 2 cases with neuropathological study].
AB  - We report two cases of thanatophoric dysplasia (TD) with detailed neuropathologic
      evaluation. One case was representative of TD type I and the other TD type II.
      The case with TD type I showed macrocephaly, narrow thoracic cage, pulmonary
      hypoplasia and bowed limbs. Radiological study showed flat vertebral bodies,
      short curved appendicular skeleton and flaring of metaphyses. The other case (TD
      type 2) showed macrocephaly, cleft palate, short limbs and cloverleaf skull.
      Radiological findings were generalized platyspondy with excessive intervertebral
      disc space heights and a large head. Microscopic examination of both cases
      revealed temporal lobe polymicrogyria, abnormalities of the hippocampus and
      heterotopic neuroglial tissue within the meninges. There were no noticeable
      differences in CNS abnormalities between TD type I and II.

PMID- 11965422
TI  - [TSH pituitary adenoma: case report].
AB  - We describe a rare case of thyroid-stimulating hormone-secreting pituitary
      adenoma in a patient with a clinical picture of hyperthyroidism, that developed
      bitemporal hemianopsia after four years of a known thyroid dysfunction. CT scan
      showed a pituitary tumor considered grade 2 and stage C according to Hardy-Vezina
      and Wilson. Treatment was surgical, initially by a transsphenoidal approach, in
      which only a biopsy was possible. The patient was then submitted to an orbital
      pterional craniotomy with sub-total resection of the tumor. Complementary
      treatment was indicated with radiotherapy.

PMID- 11965424
TI  - [Hypocalcemia and neonatal seizures: a rare case of congenital
      hypoparathyroidism].
AB  - We report the case of a white male infant, 2 months-old, with tremor and
      hypertonia since 15th day of life transferred to our service and diagnosed as
      seizures. Investigation showed hypocalcaemia (4 mg/dl) and hypomagnesemia (1.6
      mg/dL) and the infant's serum metabolic disturb was corrected by intravenous
      calcium gluconate and magnesium sulphate, but attempted to "wean" him from
      intravenous treatment led to a relapse of hypocalcemia. At this time
      hypoparathyroidism was suspected and the additional investigation confirmed this
      suspect ion. The neurologic examination revealed an irritable patient with marked
      extensor hypertonia and opisthotonos. Cranial CT and MRI scans were normal, but
      the EEG exam showed severe abnormalities. The infant was given the oral calcium
      gluconate, magnesium chloride and colecalciferol daily to maintain a normal
      calcium concentration, but the control was very difficult. The patient had an
      extend hospitalization of 6 months and death was due to repetitive infection. We
      discuss the clinical findings, imaging, EEG exam, differential diagnosis and
      treatment of this disorder.

PMID- 11965425
TI  - [Anterior instrumentation of spine in tuberculous spondylitis: Pott's disease:
      case report].
AB  - We report a case of a surgical treatment with anterior instrumentation in
      tuberculous spondylitis (Pott's disease), in a 71 years old woman, that was in
      treatment for pulmonary tuberculosis, with lumbar pain, progressive disability to
      walk, kyphotic deformity and vesical dysfunction. Magnetic resonance image
      presents a lesion in the bodies of T12 and L1, with paravertebral abscess. The
      patient was treated surgically by transthoracic-abdominal approach. The vertebral
      bodies were cut off and the spine were instrumented anteriorly with a mesh cage
      and a Z plate. This procedure permits a good arthrodesis and a immediately
      stabilization of the spine, without any complication of the infection. The
      patient was seen a year after the surgery and is free of infection, without motor
      deficit, pain or reminiscent kyphosis.

PMID- 11965426
TI  - [Primary lumbar epidural Ewing's sarcoma: case report].
AB  - We report a case of a 15-years old female with an acute paraparesis secondary of
      an epidural mass and histopathological diagnosis was consistent with an Ewing's
      sarcoma without bone compromise. An exaustive literature review showed only 17
      cases of primary lumbar epidural extraosseus Ewing's sarcoma.

PMID- 11965427
TI  - [Myelopathy due to vitamin B12 deficiency presenting as transverse myelitis].
AB  - Vitamin B12 deficiency may induce neuropathy, myelopathy, dementia and optic
      neuropathy. The diagnosis is established by vitamin B12, homocysteine and
      methylmalonic acid measurements. Myelin and axon destruction in the white matter
      of the spinal cord are observed. The posterior column of the cervical and
      thoracic level is the most common involved area. The involvement of the anterior
      column is restricted to advanced and relatively severe cases. Treatment is based
      on vitamin B12 injections, and the prognosis depends on the stage of vitamin
      deficiency and deterioration at treatment onset. We report a case with transverse
      myelitis due to vitamin B12 deficiency. This picture is relatively uncommon,
      however, we believe patients with transverse myelitis should have vitamin B12
      studies as part of the diagnosis work up.

PMID- 11965428
TI  - [Ekbom's sydrome and spasmodic torticollis: case report].
AB  - The Ekbom's syndrome, also known as delirium of parasitic infestation,
      acarophobia, delusional parasitosis, psychogenic parasitosis, is a disease of
      rare occurrence. Generally it is characterized by the firm conviction of the
      patients to be infected by worms that come out of the skin, usually from the
      scalp or even from the mouth, from the eyes or from the genital region. Most of
      the patients are elderly and female, and with frequent social isolation. Some
      cases are associated with organic diseases as hyperthyroidism, diabetes, cortical
      lesion, intoxication by medicines. To our knowledge the association between
      delusional parasitosis with spasmodic torticollis was not described in
      literature. We report the case of a 72-year-old-woman with delusional parasitosis
      associated with spasmodic torticollis.

PMID- 11965429
TI  - [Recommendations for prophylactic treatment of migraine: Consensus of the
      Sociedade Brasileira de Cefaleia].
AB  - The Brazilian Headache Society assigned an Ad Hoc Committee with the purpose of
      establishing a consensus about prophylactic treatment for migraine and of
      elaborating recommendations for professionals. The recommendations of the
      Committee are based in evidences of the world medical literature and on the
      personal experience of the members, respecting the reality of the existing
      medication resources in our country.

PMID- 11965430
TI  - Trends in codon and amino acid usage in Thermotoga maritima.
AB  - The usage of synonymous codons and the frequencies of amino acids were
      investigated in the complete genome of the bacterium Thermotoga maritima using a
      multivariate statistical approach. The GC3 content of each gene was the most
      prominent source of variation of codon usage. Surprisingly the usage of UGU and
      UGC (synonymous triplets coding for Cys, the least frequent amino acid in this
      species) was detected as the second most prominent source of variation. However,
      this result is probably an artifact due to the very low frequency of Cys together
      with the nonbiased composition of this genome. The third trend was related to the
      preferential usage of a subset of codons among highly expressed genes, and these
      triplets are presumed to be translationally optimal. Concerning the amino acid
      usage, the hydropathy level of each protein (and therefore the frequency of
      charged residues) was the main trend, while the second factor was related to the
      frequency of usage of the smaller residues, suggesting that the cell economy
      strongly influences the architecture of the proteins. The third axis of the
      analysis discriminated the usage of Phe, Tyr, Trp (aromatic residues) plus Cys,
      Met, and His. These six residues have in common the property of being the
      preferential targets of reactive oxygen species, and therefore the anaerobic
      condition of T. maritima is an important factor for the amino acid frequencies.
      Finally, the Cys content of each protein was the fourth trend.

PMID- 11965431
TI  - Rapid concerted evolution via gene conversion at the Drosophila hsp70 genes.
AB  - We analyzed nucleotide variation in the hsp70 genes of Drosophila melanogaster
      (five genes) and D. simulans (four genes) to characterize the homogenizing and
      diversifying roles of gene conversion in their evolution. Gene conversion within
      and between the 87A7 and 87C1 gene clusters homogenize the hsp70 coding regions;
      in both D. melanogaster and D. simulans, same-cluster paralogues are virtually
      identical, and large intercluster conversion tracts diminish 87A7/87C1
      divergence. Same-cluster paralogues share many polymorphisms, consistent with
      frequent intracluster conversion. Shared polymorphism is highly biased toward
      silent variation; homogenizing conversion interacts with purifying selection. In
      contrast to the coding regions, some hsp70 flanking regions show conversion
      mediated diversification. Strong reductions of nucleotide variability and linkage
      disequilibria among conversion-mediated sites in hsp70Ab and hsp70Bb alleles
      sampled from a single natural population are consistent with a selective sweep.
      Comparison of the D. melanogaster and D. simulans hsp70 genes reveals whole
      family fixed differences, consistent with rapid propagation of novel mutations
      among duplicate genes. These results suggest that the homogenizing and
      diversifying roles of conversion interact to drive dynamic concerted evolution of
      the hsp70 genes.

PMID- 11965432
TI  - Expansin-like molecules: novel functions derived from common domains.
AB  - An Arabidopsis thaliana transcript ( AtPNP-A) encoding an immunoreactant plant
      natriuretic peptide (irPNP) analog was identified and isolated. The encoded
      protein shows similarity to CjBAp12, a functionally undefined protein from citrus
      that is induced in response to blight infection. CjBAp12 shows significant
      sequence identity to domains found in the cell wall loosening expansins but has
      tested negative for cell wall loosening activity. We have thus undertaken to
      establish the evolutionary and functional relationships of irPNP-like molecules
      within the superfamily of expansins, pollen allergens, and distantly related
      molecules such as endoglucanases. We show that irPNP-like molecules are related
      to expansins and fall in two groups; one includes CjBAp12 and the other AtPNP-A.
      Members of both groups share distinct sequence motifs (K[VI]VD and [LM]SxxAFxxI)
      but do not contain the tryptophan and tyrosine rich C-terminal putative
      polysaccharide-binding domain typical of expansins or bacterial cellulases and
      hemicellulases. We argue that both irPNP-like molecules and expansin have evolved
      from primitive/ancestral glucanase-like molecules that hydrolysed the cell wall.
      Importantly, we have previously demonstrated that irPNPs act on protoplasts, that
      is plant cells without cell walls as well as microsomes, indicating that these
      novel proteins specifically interact with the plasma membrane. It follows that
      the cell wall cannot be an obligatory substrate for irPNPs. Thus, both irPNP
      function and domain structure point to these molecules having a systemic role in
      H2O and solute homeostasis.

PMID- 11965433
TI  - The chemical basis of membrane bioenergetics.
AB  - All organisms rely on chemiosmotic membrane systems for energy transduction; the
      great variety of participating proteins and pathways can be reduced to a few
      universal principles of operation. This chemical basis of bioenergetics is
      reviewed with respect to the origin and early evolution of life. For several of
      the cofactors which play important roles in bioenergetic reactions, plausible
      prebiotic sources have been proposed, and it seems likely that these cofactors
      were present before elaborate protein structures. In particular, the hydrophobic
      quinones require only a membrane-enclosed compartment to yield a minimum
      chemiosmotic system, since they can couple electron transport and proton
      translocation in a simple way. It is argued that the central features of modern
      bioenergetics, such as the coupling of redox reactions and ion translocation at
      the cytoplasmic membrane, probably are ancient features which arose early during
      the process of biogenesis. The notion of a thermophile root of the universal
      phylogenetic tree has been discussed controversially, nevertheless, thermophiles
      are interesting model organisms for reconstructing the origin of chemiosmotic
      systems, since they are often acidophiles and anaerobic respirers exploiting iron
      sulfur chemistry. This perspective can help to explain the prominent role of iron
      sulfur proteins in extant biochemistry as well as the origin of both respiration
      and proton extrusion within the context of a possible origin of life in the
      vicinity of hot vents.

PMID- 11965434
TI  - Phylogenetic analysis of vertebrate lactate dehydrogenase (LDH) multigene
      families.
AB  - In this paper we analyzed 49 lactate dehydrogenase (LDH) sequences, mostly from
      vertebrates. The amino acid sequence differences were found to be larger for a
      human-killifish pair than a human-lamprey pair. This indicates that some protein
      sequence convergence may occur and reduce the sequence differences in distantly
      related species. We also examined transitions and transversions separately for
      several species pairs and found that the transitions tend to be saturated in the
      distantly related species pair, while transversions are increasing. We conclude
      that transversions maintain a conservative rate through the evolutionary time.
      Kimura's two-parameter model for multiple-hit correction on transversions only
      was used to derive a distance measure and then construct a neighbor-joining (NJ)
      tree. Three findings were revealed from the NJ tree: (i) the branching order of
      the tree is consistent with the common branch pattern of major vertebrates; (ii)
      Ldh-A and Ldh-B genes were duplicated near the origin of vertebrates; and (iii)
      Ldh-C and Ldh-A in mammals were produced by an independent gene duplication in
      early mammalian history. Furthermore, a relative rate test showed that mammalian
      Ldh-C evolved more rapidly than mammalian Ldh-A. Under a two-rate model, this
      duplication event was calibrated to be approximately 247 million years ago (mya),
      dating back to the Triassic period. Other gene duplication events were also
      discovered in Xenopus, the first duplication occurring approximately 60-70 mya in
      both Ldh-A and Ldh-B, followed by another recent gene duplication event,
      approximately 20 mya, in Ldh-B.

PMID- 11965435
TI  - Codon usage by transposable elements and their host genes in five species.
AB  - We compared the codon usage of sequences of transposable elements (TEs) with that
      of host genes from the species Drosophila melanogaster, Arabidopsis thaliana,
      Caenorhabditis elegans, Saccharomyces cerevisiae, and Homo sapiens. Factorial
      correspondence analysis showed that, regardless of the base composition of the
      genome, the TEs differed from the genes of their host species by their AT
      richness. In all species, the percentage of A + T on the third codon position of
      the TEs was higher than that on the first codon position and lower than that in
      the noncoding DNA of the genomes. This indicates that the codon choice is not
      simply the outcome of mutational bias but is also subject to selection
      constraints. A tendency toward higher A + T on the third position than on the
      first position was also found in the host genes of A. thaliana, C. elegans, and
      S. cerevisiae but not in those of D. melanogaster and H. sapiens. This strongly
      suggests that the AT choice is a host-independent characteristic common to all
      TEs. The codon usage of TEs generally appeared to be different from the mean of
      the host genes. In the AT-rich genomes of Arabidopsis thaliana, Caenorhabditis
      elegans, and Saccharomyces cerevisiae, the codon usage bias of TEs was similar to
      that of weakly expressed genes. In the GC-rich genome of D. melanogaster,
      however, the bias in codon usage of the TEs clearly differed from that of weakly
      expressed genes. These findings suggest that selection acts on TEs and that TEs
      may display specific behavior within the host genomes.

PMID- 11965436
TI  - The impact of message mutation on the fitness of a genetic code.
AB  - The Standard Genetic Code is organized such that similar codons encode similar
      amino acids. One explanation suggested that the Standard Code is the result of
      natural selection to reduce the fitness "load" that derives from the mutation and
      mistranslation of protein-coding genes. We review the arguments against the
      mutational load-minimizing hypothesis and argue that they need to be reassessed.
      We review recent analyses of the organization of the Standard Code and conclude
      that under cautious interpretation they support the mutational load-minimizing
      hypothesis. We then present a deterministic asexual model with which we study the
      mode of selection for load minimization. In this model, individual fitness is
      determined by a protein phenotype resulting from the translation of a mutable set
      of protein-coding genes. We show that an equilibrium fitness may be associated
      with a population with the same genetic code and that genetic codes that assign
      similar codons to similar amino acids have a higher fitness. We also show that
      the number of mutant codons in each individual at equilibrium, which determines
      the strength of selection for load minimization, reflects a long-term
      evolutionary balance between mutations in messages and selection on proteins,
      rather than the number of mutations that occur in a single generation, as has
      been assumed by previous authors. We thereby establish that selection for
      mutational load minimization acts at the level of an individual in a single
      generation. We conclude with comments on the shortcomings and advantages of load
      minimization over other hypotheses for the origin of the Standard Code.

PMID- 11965437
TI  - Phylogenetic analysis of invertebrate lysozymes and the evolution of lysozyme
      function.
AB  - We isolated and sequenced the cDNAs coding for lysozymes of six bivalve species.
      Alignment and phylogenetic analysis showed that, together with recently described
      bivalve lysozymes, the leech destabilase, and a number of putative proteins from
      extensive genomic and cDNA analyses, they belong to the invertebrate type of
      lysozymes (i type), first described by Jolles and Jolles (1975). We determined
      the genomic structure of the gene encoding the lysozyme of Mytilus edulis, the
      common mussel. We provide evidence that the central exon of this gene is
      homologous to the second exon of the chicken lysozyme gene, belonging to the c
      type. We propose that the origin of this domain can be traced back in evolution
      to the origin of bilaterian animals. Phylogenetic analysis suggests that i-type
      proteins form a monophyletic family.

PMID- 11965438
TI  - Rapid evolution of the male-specific antibacterial protein andropin gene in
      Drosophila.
AB  - Andropin, which encodes an antibacterial protein, is closely linked to the
      Cecropin gene cluster of D. melanogaster. Andropin and Cecropins are considered
      to have originated from one common ancestor. However, the expression pattern of
      Andropin is distinct from that of Cecropins, being restricted to the adult male
      ejaculatory duct. To elucidate the evolutionary process of Andropin, we have
      sequenced Andropin genes from D. melanogaster and its closely related species. In
      D. melanogaster, the nucleotide diversity of Andropin is remarkably low compared
      to that of Cecropin. In contrast, nonsynonymous substitutions of Andropin are
      conspicuously frequent between species. From genomic Southern analysis, Andropin
      like genes are present in at least the melanogaster species subgroup. The series
      of present results suggests that Andropin was born in the course of constructing
      the Drosophila Cecropin gene family and then started to evolve rapidly, in
      contrast to Cecropins.

PMID- 11965439
TI  - C6-like and C3-like molecules from the cephalochordate, amphioxus, suggest a
      cytolytic complement system in invertebrates.
AB  - The mammalian immune system has cytotoxic mechanisms, both cellular and humoral,
      that destroy the membrane integrity of target cells. The main effector molecules
      of these cytolytic mechanisms-perforin, used by killer lymphocytes, and the
      membrane attack complex (MAC) components of the complement system-share a unique
      module called the MAC/perforin module. Until now, both immunological cytotoxicity
      and the MAC/perforin module have been reported only in jawed vertebrates. Here,
      we report the identification of a protein containing the MAC/perforin module from
      the invertebrate cephalochordate, amphioxus ( Branchiostoma belcheri), using
      expressed sequence tag (EST) analysis of the notochord. The deduced amino acid
      sequence of this molecule is most similar to the primary structure of human
      complement component C6 and is designated AmphiC6. AmphiC6 shares a unique
      modular structure, including the MAC/perforin module, with human C6 and other MAC
      components. Another EST clone predicts the presence of a thioester-containing
      protein with the closest structural similarity to vertebrate C3 (therefore
      designated AmphiC3). AmphiC3 retains most of the functionally important residues
      of vertebrate C3 and is shown by phylogenetic analysis to be derived directly
      from the common ancestor of vertebrate C3, C4, and C5. Only opsonic activity has
      been assigned to the invertebrate complement system until now. Therefore, this is
      the first molecular evidence for complement-mediated immunological cytotoxicity
      in invertebrates.

PMID- 11965440
TI  - Recent evolutionary history of human immunodeficiency virus type 1 subtype B:
      reconstruction of epidemic onset based on sequence distances to the common
      ancestor.
AB  - We obtained and studied HIV-1 sequences with a known sampling year from three
      outbreaks of the HIV-1 epidemic: 141 env V3 (270 nt) sampled between 1984 and
      1992 and 117 pol prot/RT (804 nt) sequences sampled between 1986 and 1999 from
      Dutch homosexual men and injecting drug users (IDUs), as well as 77 env V3
      sequences sampled between 1983 and 1994 in the United States. Since retrospective
      serological and/or epidemiological data on these populations are available,
      providing estimates of the dates of the onset of the HIV-1 epidemics, we had the
      opportunity to test different phylogenetic models for their accuracy in deriving
      the recent evolutionary history of HIV-1 subtype B and the onset date of the HIV
      1 epidemic. We observed that, in any given year, individual sequences vary widely
      in their distances to the common ancestor, and sequences close to the ancestors
      were found decades after the onset of the epidemic. Nevertheless, the mean
      evolutionary distances of virus strains to ancestors were increasing
      significantly during the course of the studied epidemics, which indicates that
      the molecular clock is operational in the recent evolution of HIV-1. When the
      relationship between the sampling years of sequences and their nucleotide
      distances to the common ancestor was extrapolated to the past, analysis of pol
      sequences provided accurate estimates of the onset years of the epidemics,
      whereas analysis of V3 sequences by the maximum-likelihood or neighbor-joining
      methods led to an overestimation of the age of the epidemics. Separate analysis
      of nonsynonymous and synonymous distances revealed that this overestimation
      results from nonsynonymous substitutions, whose numbers were not increasing
      significantly in all three virus populations over the observation period. In
      contrast, analysis of synonymous env V3 distances provided accurate estimates of
      the onset years for the outbreaks we studied.

PMID- 11965441
TI  - Group I introns from Zygomycota: evolutionary implications for the fungal IC1
      intron subgroup.
AB  - The origins of fungal group I introns within nuclear small-subunit (nSSU) rDNA
      are enigmatic. This is partly because they have never been reported in basal
      fungal phyla (Zygomycota and Chytridiomycota), which are hypothesized to be
      ancestral to derived phyla (Ascomycota and Basidiomycota). Here we report group I
      introns from the nSSU rDNA of two zygomycete fungi, Zoophagus insidians
      (Zoopagales) and Coemansia mojavensis (Kickxellales). Secondary structure
      analyses predicted that both introns belong to the IC1 subgroup and that they are
      distantly related to each other, which is also suggested by different insertion
      sites. Molecular phylogenetic analyses indicated that the IC1 intron of Z.
      insidians is closely related to the IC1 intron inserted in the LSU rDNA of the
      basidiomycete fungus Clavicorona taxophila, which strongly suggests interphylum
      horizontal transfer. The IC1 intron of C. mojavensis has a low phylogenetic
      affinity to other fungal IC1 introns inserted into site 943 of nSSU rDNA
      (relative to E. coli 16S rDNA). It is noteworthy that this intron contains a
      putative ORF containing a His-Cys box motif in the antisense strand, a hallmark
      for nuclear-encoded homing endonucleases. Overall, molecular phylogenetic
      analyses do not support the placement of these two introns in basal fungal IC1
      intron lineages. This result leads to the suggestion that fungal IC1 introns
      might have invaded or been transferred laterally after the divergence of the four
      major fungal phyla.

PMID- 11965442
TI  - Plasmin/plasminogen system in colorectal cancer.
AB  - Pericellular proteolysis plays a crucial role in tumor cell invasion. The
      controlled degradation of the extracellular matrix by tumor cell-associated
      proteases allows tumor cells to invade surrounding tissues and gain access to the
      circulation. One of the main protease systems involved in tumor cell invasion and
      metastasis is the plasminogen/plasmin system (PPS). The components of the PPS
      include the urokinase plasminogen activator (uPA), its cell surface receptor
      urokinase plasminogen activator receptor (uPAR), and its naturally occurring
      inhibitors, plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2). Increases
      in tumor and serum levels of uPA, uPAR, and PAI-1 are associated with a worse
      prognosis in patients with colon cancer. Use of these proteins as either tumor or
      serum markers may allow more accurate determination of the prognosis in colon
      cancer patients. Furthermore, these proteins appear to be attractive as targets
      for the biologic therapy of colon cancer.

PMID- 11965443
TI  - Gene transfer strategies for metabolic diseases.
AB  - Recent advances in molecular genetics and biotechnology will revolutionize the
      practice of medicine and surgery during the next decade. Surgeons must understand
      and begin to use the new technologies in the study of surgical biology and
      patient care. A brief overview of the principles of gene transfer and how this
      technology is used for treating metabolic disease is presented. Two examples of
      how recombinant viruses (vectors) can be used to study fundamental biology in the
      liver and pancreas are given. Familial hypercholesterolemia is used as a paradigm
      for a clinical gene transfer study and underscores the importance of surgeons in
      the development of novel therapeutic strategies.

PMID- 11965444
TI  - Does intraoperative quick parathyroid hormone assay improve the results of
      parathyroidectomy?
AB  - Preoperative sestamibi (MIBI) and ultrasonography (US) are used to localize
      parathyroid tumors in patients with primary hyperparathyroidism (pHPT). The
      intraoperative quick PTH assay (qPTH) has been recommended to determine whether
      all hyperfunctioning parathyroid tissue has been removed. We questioned whether
      qPTH improves the results of parathyroidectomy in patients with pHPT. We analyzed
      115 unselected patients with pHPT without a family history or multiple endocrine
      neoplasia but who had undergone parathyroidectomy. All 115 patients had
      successful operations without complications. Of these patients, 88 (77%) had
      solitary adenomas, 13 had double adenomas, 1 had triple adenomas, 12 had
      hyperplasia, and 1 had carcinoma. Overall, MIBI was correct in 72% (76/106), US
      in 49% (49/99), and qPTH in 80% (92/115). For preoperative studies showing a
      single tumor, MIBI was correct in 83% (73/88), US was correct in 71% (45/63), and
      combined MIBI and US were correct in 95% (37/39). Adding qPTH in this subgroup
      did not improve the successful focused approach: 70% for MIBI, 65% for US, and
      87% for combined MIBI and US. However, adding qPTH improved the overall success
      of parathyroidectomy (MIBI 92%, US 86%, combined MIBI and US 97%), but at the
      cost of unnecessary further exploration (MIBI 13%, US 6%, combined MIBI and US
      8%). We conclude that when the same solitary tumor is identified by both MIBI and
      US, a focused exploration can be done with a 95% success rate. Adding qPTH to
      MIBI or US can improve the success rate but at a significant cost. General
      exploration of all parathyroid glands, however, has the highest success rate
      (100%).

PMID- 11965445
TI  - Mechanisms of pulmonary microvascular dysfunction during severe burn injury.
AB  - Even in the absence of inhalational injury, acute lung injury is a common cause
      of morbidity and mortality for patients sustaining severe burns. Other than
      general supportive measures, there are few therapeutic options for improving
      survival in these critically ill patients. Numerous clinical and laboratory
      studies have implicated tumor necrosis factor (TNF)-a and neutrophils as
      important participants in the pathogenesis of burn-induced lung injury. There is,
      however, little information regarding the mechanism by which these and other pro
      inflammatory mediators affect the movement of fluid and protein across the
      microvascular barrier into the interstitium of the lung. In addition to reviewing
      the evidence implicating TNF-a and neutrophils in the pathophysiology of burn
      induced lung injury, this report summarizes current theories regarding potential
      mechanisms by which these mediators may alter microvascular barrier function to
      lead ultimately to the development of pulmonary edema.

PMID- 11965446
TI  - Familial nonmedullary thyroid carcinoma characterized by multifocality and a high
      recurrence rate in a large study population.
AB  - First-degree relatives of persons with thyroid cancer are known to be at
      relatively high risk for the disease. To better understand the clinicopathologic
      characteristics of familial nonmedullary thyroid carcinoma (FNMTC), we carried
      out a retrospective study in which we identified individuals treated at our
      institution who had at least one first-degree relative with the disease. We used
      data obtained from our patient records to compare the features of 258 cases of
      the disease with the features of sporadic papillary or follicular thyroid
      carcinoma in another group of patients. The 258 patients represented 154 families
      and were selected from among 6458 patients with papillary or follicular thyroid
      carcinoma who underwent thyroidectomy between 1946 and 2000. Compared to the
      patients with sporadic disease, the FNMTC patients were more likely to have
      intraglandular dissemination (28.5% vs. 40.7%; p < 0.0001) and multiple benign
      nodules (29.8% vs. 41.5%; p <0.0001). There were no significant differences
      between the two types of patients in terms of gender, age, tumor diameter,
      adhesion to or invasion of the surrounding tissues, macroscopic metastasis
      observed at surgery, histology, presence of single benign nodules, presence of
      chronic thyroiditis, microscopic metastasis, or rate of lymph node metastasis.
      Recurrence was statistically frequent in the FNMTC patients compared with that in
      the sporadic disease patients (16.3% vs. 9.6%; p = 0.0005), and the disease-free
      survival rate was significantly poorer in the FNMTC patients (p = 0.0041 by the
      Wilcoxon test and p <0.0001 by the log-rank test). No significant difference in
      the overall survival rate was found between the two groups. Multivariate analysis
      by Cox's proportional hazards method showed FNMTC to be an independent predictor
      of shorter disease-free survival (risk ratio 1.88; confidence interval 1.35-2.54;
      p = 0.0003). Locoregional recurrence in the ipsilateral or contralateral lymph
      nodes and contralateral thyroid lobe was significantly more frequent in the FNMTC
      patients than in the sporadic disease patients, whereas no difference was found
      regarding distant metastases. We conclude that FNMTC is a clinically distinct
      entity with an aggressive nature. Because of the frequent presence of benign
      nodules, multifocality, and high rate of locoregional recurrence, total or near
      total thyroidectomy with modified radical neck dissection in FNMTC patients is
      recommended.

PMID- 11965447
TI  - Transcatheter microcoil embolotherapy for ruptured pseudoaneurysm following
      pancreatic and biliary surgery.
AB  - PURPOSE: To evaluate the outcome of transcatheter microcoil embolotherapy for
      bleeding pseudoaneurysms complicating major pancreatic and biliary surgery.
      MATERIALS AND METHODS: Over an 8-year period, 8 patients were encountered who
      developed massive bleeding from pseudoaneurysms 15-64 days (mean 31 days)
      following major pancreatic and biliary surgery. Urgent transcatheter microcoil
      embolotherapy was performed in all 8 patients. RESULTS: Transcatheter
      embolotherapy was successful in 7 of 8 patients (88%) but failed in one due to
      development of disseminated intravascular coagulation. One patient developed
      recurrent bleeding 36 days after the first embolotherapy from a newly developed
      pseudoaneurysm, which was again treated successfully with embolization. Two
      patients subsequently underwent additional surgery for residual pathology. Three
      of the 7 patients with successful embolotherapy were alive at 10-96 months, 4
      patients died of associated malignancies 4-20 months after embolotherapy.
      CONCLUSION: Transcatheter microcoil embolotherapy is effective for bleeding
      pseudoaneurysms complicating pancreatic and biliary surgery, and should be
      considered the first treatment of choice.

PMID- 11965448
TI  - The discipline of gastrointestinal surgery can be strengthened through
      cooperation among its professional societies.

PMID- 11965450
TI  - Management of major bile duct injury associated with laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Bile duct injury is a major complication of laparoscopic
      cholecystectomy. The purpose of this study was to evaluate our management
      strategy and outcomes for the treatment of such injuries. METHODS: We studied 54
      consecutive patients who had de novo bile duct injury (n = 20) or prior biliary
      injury repair (n = 34) associated with laparoscopic cholecystectomy. All patients
      were managed using a multidisciplinary approach. RESULTS: Definitive operation,
      almost always Roux-en-Y hepaticojejunostomy, was required in 85% of patients. We
      inserted external percutaneous biliary catheters in 98% of cases prior to
      surgery. There were no operative deaths, and the 30-day complication rate was
      20%. Eight patients (15%) were managed nonoperatively. Overall, 96% of patients
      had no long-term, objectively definable biliary sequelae. CONCLUSIONS: Treatment
      of bile duct injury associated with laparoscopic cholecystectomy is optimally
      done using a multidisciplinary approach. Surgical reconstruction is required in
      most cases and can be safely accomplished with minimal morbidity and excellent
      long-term outcomes.

PMID- 11965449
TI  - The diagnostic and therapeutic roles of colonoscopy: a review.

PMID- 11965451
TI  - Are the favorable outcomes of splenectomy predictable inpatients with idiopathic
      thrombocytopenic purpura (ITP)?
AB  - BACKGROUND: Historically, splenectomy has been an accepted procedure in the
      management of immune thrombocytopenic purpura (ITP). However, it is also true
      that the response to splenectomy in patients with ITP seems to be unpredictable.
      Therefore, the purpose of this study was to identify clinical variables that
      might predict a favorable response to splenectomy in patients with ITP. METHODS:
      Data were collected retrospectively for 40 adult patients with ITP who underwent
      laparoscopic (LS) and open (OS) splenectomy at Emory University Hospital between
      1992 and 1999. Demographics and outcomes were recorded. Age, sex, disease
      duration, comorbidities (ASA > 2), previous response to steroids and/or other
      medications, and preoperative platelet count were analyzed by univariate (t-test,
      Fisher's exact test) and multivariate statistical methods. RESULTS: Of the 20
      patients in each group, improved platelet counts were noted in 18 patients (90%)
      in the LS group and 20 patients (100%) in the OS group. Follow-up (16 +/- 3
      months) was obtained in 19 LS patients (95%) and 16 OS patients (80%), with 84%
      and 87.5% sustained response rates, respectively. After univariate analysis, two
      variables (age and disease duration) were found to be significantly related to
      the outcome of splenectomy (p <lt; 0.01). However, after multiple logistic
      regression analysis, only disease duration (relative risk = 1.083; CI, 1.004
      1.167) was an independent prognostic factor for a sustained response to
      splenectomy. CONCLUSION: These results suggest that the response to splenectomy
      (laparoscopic and open) in patients with ITP cannot be adequately predicted on
      the basis of presplenectomy clinical variables. However, disease duration and
      patient age should be taken into consideration when selecting patients for
      splenectomy.

PMID- 11965452
TI  - Laparoscopic right donor nephrectomy: technique and comparison with left
      nephrectomy.
AB  - BACKGROUND: Laparoscopic donor nephrectomy (LDN) preferentially involves the left
      kidney to optimize vessel length, but occasionally, right nephrectomy is
      preferred. Right LDN differs markedly in anatomic relations and the need for a
      fourth port. This retrospective study compares donor outcomes and graft function
      of right and left LDN and describes the technique. METHODS: Consecutive patients
      undergoing right LDN from March 26, 1996 to December 31, 2000 were compared with
      those undergoing left LDN. Age, height, weight, body mass index, creatinine,
      creatinine clearance, operative time, warm ischemia time, analgesic requirements,
      serial postoperative creatinine, time to diet resumption, and hospital stay were
      compared. A second cohort matched for age, gender, race, and temporal left LDN
      also were compared with the group undergoing right LDN. RESULTS: No significant
      differences were found for any of the parameters measured. CONCLUSION: This study
      demonstrates that despite substantial differences in the procedures, donor
      outcome and graft survival are similar for right and left LDN.

PMID- 11965453
TI  - Clinical evaluation of a newly developed endoscopic resection device
      (Rotoresect): physical principle and first clinical results.
AB  - BACKGROUND: Endoscopic resection techniques on benign prostatic tissue aim at a
      high ablation rate and a minimal bleeding rate. Although commercial resection
      electrodes are effective, they either cause high blood loss (loop electrode) or
      reduce the bleeding rate with a compromised ablation rate (electrovaporization
      electrode). To resolve these problems, a new electrosurgical resection device,
      The Rotoresect, has been developed. METHODS: The Rotoresect incorporates a
      specially designed working element. The resection electrode is driven by a
      micromotor with a high-frequency current that enables simultaneous coagulation
      and vaporization during rotoresection. To date, 40 patients with benign prostatic
      hyperplasia have undergone transurethral rotoresection of the prostate with this
      new device. RESULTS: The actively rotating resection electrode enables tissue
      coagulation and vaporization as well as mechanical tissue ablation. Only slight
      bleeding was observed during the entire resection procedure. Postoperatively, no
      significant changes in hemoglobin and sodium concentration were detected. The
      deobstructive effect of the Rotoresect was comparable to that of the standard
      loop. CONCLUSIONS: The simultaneous tissue vaporization, coagulation, and
      mechanical removal by the Rotoresect enables a high ablation rate combined with
      minimal blood loss. Initial clinical results gained in the transurethral
      resection of benign prostatic tissue are promising.

PMID- 11965454
TI  - Laparoscopic reoperative antireflux surgery.
AB  - BACKGROUND: Antireflux operations for gastroesophageal reflux disease whether
      performed open or laparoscopically can fail and may require reoperation to
      control new, recurrent symptoms or operation-related complications. We report our
      experience with the laparoscopic reoperation for failed antireflux procedures.
      METHODS: Between 1995 and 2000, 37 patients underwent laparoscopic reoperative
      antireflux procedures. The mean age and weight were 52 years and 181.5 pounds.
      The main presenting symptoms were heartburn (n = 18), respiratory reflux (n = 4),
      chest pain (n = 3), regurgitation (n = 1), and dysphagia (n = 10). The mean
      duration between the first operation and recurrence of symptoms was 18 months,
      and the duration between the two procedures was 25 months. The operation was
      completed laparoscopically in 32 patients (86.5%): Nissen fundoplication (n = 27)
      and Toupet fundoplication (n = 9). RESULTS: Intraoperative and postoperative
      complications occurred in 6 and 14 patients, respectively. Fundoplication
      disruption was the most common cause of primary surgery failure. The mean
      hospital stay was 4 days. At a mean follow-up of 26.5 months, results were
      excellent to good (65%), fair (21.5%), and poor (13.5%). CONCLUSION: Laparoscopic
      reoperative antireflux procedures are technically feasible with acceptable
      preliminary results.

PMID- 11965455
TI  - Preoperative determinants of an esophageal lengthening procedure in laparoscopic
      antireflux surgery.
AB  - BACKGROUND: In a minority of patients undergoing antireflux surgery, an
      esophageal lengthening procedure is required to reduce the gastroesophageal
      junction (GEJ) below the esophageal hiatus. We evaluated risk factors associated
      with an irreducible GEJ to identify clinical features that were predictive of the
      need for a Collis gastroplasty in patients undergoing laparoscopic antireflux
      surgery. METHODS: Patients who required a Collis gastroplasty during a
      laparoscopic antireflux procedure (defined as the inability to reduce the GEJ >
      2.5 cm below the esophageal hiatus despite extensive mobilization of the
      mediastinal esophagus) were compared to a random sample of patients who did not
      have a Collis gastroplasty. Predictors of the need for an esophageal lengthening
      procedure were identified using logistic regression modeling. Risks were
      expressed as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Twenty
      patients who had a Collis gastroplasty were compared to 133 patients who had
      adequate esophageal length. The presence of a stricture (OR 3.0; 95% CI 1.0,
      9.7), paraesophageal hernia (OR 3.5; 95% CI 1.3, 9.6), Barrett's esophagus (OR
      3.7, 95% CI 1.3, 10.7), and re-do antireflux surgery (OR 6.4; 95% CI 2.0, 20.7)
      were associated with the need for gastroplasty. Patients with none of these
      factors were extremely unlikely to require a gastroplasty (OR 0.08; 95% CI 0.02,
      0.34). CONCLUSION: Patients undergoing laparoscopic antireflux surgery who are at
      high risk of needing an esophageal lengthening procedure can be easily identified
      preoperatively using simple clinical characteristics.

PMID- 11965456
TI  - Endoscopic surgery in weightlessness: the investigation of basic principles for
      surgery in space.
AB  - BACKGROUND: Performing a surgical procedure in weightlessness, also called 0
      gravity (0-g), has been shown to be no more difficult than in a 1-g environment
      if the requirements for the restraint of the patient, operator, surgical
      hardware, are observed. The performance of laparoscopic and thorascopic
      procedures in weightlessness, if feasible, would offer several advantages over
      the performance of an open operation. Concerns about the feasibility of
      performing minimally invasive procedures in weightlessness have included impaired
      visualization from the absence of gravitational retraction of the bowel
      (laparoscopy) or thoracic organs (thoracoscopy) as well as obstruction and
      interference from floating debris such as blood, pus, and irrigation fluid. The
      purpose of this study was to determine the feasibility of performing laparoscopic
      and thorascopic procedures and the degree of impaired surgical endoscopic
      visualization in weightlessness. METHODS: From 1993 to 2000, laparoscopic and
      thorascopic procedures were performed on 10 anesthetized adult pigs weighing
      approximately 50 kg in the National Aeronautics and Space Administration (NASA)
      Microgravity Program using a modified KC-135 airplane. The parabolic simulation
      system for advanced life support was used in this project, and 20 to 40 parabolas
      were used for laparoscopic or thorascopic investigation, each containing
      approximately 30 s of 0-g alternating with 2-g pullouts. The animal model was
      restrained in the supine position on a floor-level Crew Medical Restraint System,
      and the abdominal cavity was insufflated with carbon dioxide. The intraabdominal
      and intrathoracic anatomy was visualized in the 1-g, 0-g, and 2-g periods of
      parabolic flight. Bleeding was created in the animals, and the behavior of the
      blood in the abdominal and thoracic cavities was observed. In the thoracic
      cavity, gas insufflation and mechanical retraction was used at times unilaterally
      to decrease pulmonary ventilation enough to increase the thoracic domain.
      RESULTS: Visualization was improved in laparoscopy, from tethering of the bowel
      by the elastic mesentery, and from the strong tendency for debris and blood to
      adhere to the abdominal wall because of surface tension forces. The lack of
      adequate thoracic domain made thorascopy more difficult. Fluid in the thoracic
      cavity did not impair visualization because the fluid at 0-g does not loculate
      posteriorly, but disperses along the thoracic wall and mediastinal reflections.
      CONCLUSIONS: Performing minimally invasive procedures instead of open surgical
      procedures in a weightless environment has theoretical advantages, especially in
      the ability to prevent cabin atmosphere contamination from surgical fluids
      (blood, pus, irrigation). Visualization will become more important and practical
      as the endoscopic hardware is miniaturized from its current form, as endoscopic
      technology becomes more advanced, and as more surgically capable medical crew
      officers are present in future long-duration space exploration missions.

PMID- 11965457
TI  - Obesity and laparoscopic repair of ventral hernias.
AB  - BACKGROUND: Laparoscopic ventral hernia repair (LVHR) is gaining acceptance and
      compares favorably with open repair. Patients who are morbidly obese (MO)
      traditionally have been considered poor surgical candidates for ventral hernia
      repair because of their associated comorbidities and risk of postoperative wound
      infection and hernia recurrence. In this study we evaluated our experience with
      LVHR in patients who are obese and those who are morbidly obese. METHODS: All 64
      patients undergoing LVHR at the University of Kentucky between September 1997 and
      October 2000, representing 66 hernias, were entered prospectively into a
      database. Data before, during, and after surgery were collected as well as follow
      up data. Patients were divided into three groups on the basis of body mass index
      (BMI): normal to overweight (BMI < or = 29); obese (BMI 30-39), and MO (BMI > or
      = 40). RESULTS: There were 16 patients in the MO group, most of them women. The
      mean BMI was 43.9 (range, 40-60), and the mean age was 45.6 years (range, 25-68
      years). The location of defects was similar among the groups, as were the number
      of prior repairs. The operative time and length of stay for the MO group tended
      to be longer than for the other two groups. Five minor complications occurred in
      the MO group. During a follow-up period ranging from 1 to 35 months, there were
      no recurrences. CONCLUSION: Laparoscopic repair of ventral hernias in patients
      who are morbidly obese is both safe and feasible, and can be performed with
      minimal morbidity. At this writing, there have been no recurrences, but long-term
      follow-up evaluation is required.

PMID- 11965458
TI  - Medium-term results after cholecystectomy in patients younger than 10 years.
AB  - BACKGROUND: Gallbladder stones are a well-known and widely studied problem in
      children. Hematological disorders are the most common diseases that can cause
      cholelithiasis. However, in the last few years, the proportion of children with
      idiopathic cholelithiasis has increased 50%. Herein, we present a prospective
      study on laparoscopic cholecystectomy in a selected group of patients aged < 10
      years. METHODS: Fifty-eight patients aged < 10 years underwent laparoscopic
      cholecystectomy for stones in the period 1992-99. The female/male ratio was 1.5,
      the mean age was 8 years (range, 2-10), and the mean weight was 30 kg. In all
      patients, parenteral nutrition, fasting state, and prolonged use of antibiotics
      had been suspended for > or = 6 months, and conservative treatment had been tried
      for > or = 12 months in the absence of symptoms of stone migration. All the
      patients were followed up after surgery: clinically at 1,6,12, and 36 months and
      by ultrasound at 1, 12, and 36 months. Liver function and hematological tests
      were performed in case of symptoms or if hemolytic disorders were the cause of
      stones. RESULTS: The mean operative time was 63 min (range, 30-120) in children
      undergoing cholecystectomy alone and 150 min in children undergoing associated
      splenectomy. There were no major complications or reoperations. Minor
      complications included bleeding from accessory cystic artery (n = 3) and
      insufflation of the omentum (n = 2). One case was converted to an open procedure
      due to technical problems. All the children were followed up and no complications
      were observed. CONCLUSION: We consider the laparoscopic approach the gold
      standard for cholecystectomy in children. This procedure does not have a
      complication rate any higher than open cholecystectomy, and patient follow-up is
      as good as that of open surgery. Previous abdominal surgery is not a
      contraindication to laparoscopy.

PMID- 11965459
TI  - Laparoscopic colectomy for sigmoid diverticulitis in obese and nonobese patients:
      a prospective comparative study.
AB  - BACKGROUND: The aim of this prospective comparative study was to assess the
      outcome of laparoscopic colectomy for sigmoid diverticulitis in normal-weight,
      overweight, and obese patients. METHODS: From January 1995 to December 2000, all
      patients (n = 77) undergoing an elective colectomy for sigmoid diverticulitis
      were enrolled in the study. The patients were divided into three groups: Group 1
      (n = 29) consisted of healthy, normal-weight patients (BMI, 18-24.9); group 2 (n
      = 27) consisted of overweight patients (BMI, 25.0-29.9); group 3 (n = 21)
      consisted of obese patients (BMI, 30.0-39.9). Groups 2 and 3 were compared with
      group 1. RESULTS: Group 1 was comprised of 13 women and 16 men with a mean age of
      58.4 years (range, 37-78); group 2, was comprised of 13 women and 14 men with a
      mean age of 55.2 years (range, 31-83); group 3, was comprised of 13 women and 14
      men with a mean age of 54.1 years (range, 33-86). There was no difference among
      the three groups in ASA classification, postoperative length of hospital stay, or
      inpatient rehabilitation. The operating time did not differ for groups 1 and 2
      (187 vs 210 min, p = 0.6), but it was shorter in group 1 than in group 3 (187 vs
      247 min, p = 0.003). The conversion rate was similar for all three groups: 17.2%
      in group 1, 14.8% in group 2, and 19% in group 3. The postoperative period during
      which parenteral analgesics were required did not differ between groups 1 and 2
      (5.7 vs 7.7 days, p = 0.1), but it was longer for group 3 (8.5 days, p = 0.03).
      The morbidity rate was similar for all three groups: 17.2% in group 7, 14.8% in
      group 2, and 19% in group 3. There were no perioperative deaths. CONCLUSIONS:
      Data from the present study suggest that laparoscopic colectomy for sigmoid
      diverticulitis can be applied safely in overweight and obese patients

PMID- 11965460
TI  - Systematic review of laparoscopic surgery for colorectal malignancy.
AB  - BACKGROUND: We set out to evaluate the current literature on the use of
      laparoscopic surgery for malignant colorectal disease and identify its place in
      current practice. METHODS: We performed a systematic review of the literature
      that included papers published from January 1991 to March 1997. Inclusion
      criteria were used to select the most robust studies. The quality of each study
      was assessed against predefined criteria and weighted according to hierarchy of
      evidence and sample size. RESULTS: The published literature was found to be low
      in the hierarchy of evidence. Of the 157 studies located, only 42 papers were
      found to be of sufficiently high quality to be included in the review. Only 13 of
      these 42 papers concentrated specifically on malignant colorectal disease. We
      noted the following findings: The average age of patients was 63.2 years. The
      most frequently reported contraindication to laparoscopic surgery was obesity.
      Conversion rate to open procedure varied between 1.5% and 48%. The most common
      postoperative complication was wound infection. Thirty-day mortality varied
      between 0 and 5.1%. Disease stage and pathology were poorly reported. Patient
      recovery benefits varied. It was not possible to identify the effectiveness,
      safety, survival outcome, or cost of laparoscopic surgery for colorectal
      malignancy in comparison to open surgery. CONCLUSIONS: Six years after the first
      report of laparoscopic surgery, studies low in the hierarchy of evidence continue
      to be reported. This reflects a lack of control following the introduction of
      this new technology. The majority of reports continue to be feasibility studies.
      The variable nature and content of the literature demonstrate the lack of
      standardization and the absence of an agreed core minimum data set. The benefit
      of laparoscopic surgery for malignant colorectal disease remains unclear. Until
      the mechanisms of port site recurrences are elucidated and long-term data on
      survival outcomes become available, laparoscopic surgery for malignant disease
      should be carried out only in the context of a large, multicenter randomized
      controlled trial.

PMID- 11965461
TI  - The role of lymphoscintigraphy in rectal laparoscopic surgery: can the sentinel
      node concept be applied to rectal carcinoma?
AB  - BACKGROUND: Lymphadenectomy for rectal cancer, whether by open surgery or
      laparoscopy, is still a controversial subject. If we consider that approximately
      20% of patients have nodal obturator metastases, then we must concede that
      extended lymphadenectomy is useless in the other 80% of patients. We set out to
      determine whether lymphoscintigraphy could show the lymphatic drainage from the
      cancer toward the obturator lymph nodes and thus help us to select the patients
      who would benefit by their removal. We also analyzed the possibility of applying
      the concept of the sentinel node to the treatment of rectal cancer. METHODS:
      Among 42 people who underwent laparoscopy for rectal cancer 11 patients with TNM
      stages T2-T3N0M0 were studied by CT & MRI, rectal ultrasonography, and
      lymphoscintigraphy with a colloidal injection of human albumin labeled with 99mTc
      at the base of the neoplasm. Afterward, the 11 patients underwent a
      lymphadenectomy that extended to the obturator nodes. RESULTS: In two patients,
      lymphoscintigraphy showed lymphatic drainage toward the obturator nodes. In one
      case, there were metastases. Lymphoscintigraphy did not show lymphatic drainage
      toward the obturator nodes in any of the other patients, and there were no
      metastases among them. It was not possible to identify a sentinel node.
      CONCLUSION: Lymphoscintigraphy can be used to select patients with rectal cancer
      who will be helped by a lymphadenectomy extended to the obturator nodes. However,
      the concept of the sentinel node cannot be applied to rectal cancer.

PMID- 11965462
TI  - Use of the Polyflex stent in the palliative therapy of esophageal carcinoma:
      results in 14 cases and review of the literature.
AB  - BACKGROUND: Several prospective randomized trials have shown that self-expanding
      stents have advantages over conventional plastic tubes. Nevertheless, the optimal
      stent has not yet been developed. The Polyflex stent is a completely new model
      that represents an improvement over the old metal stents. We have used this stent
      in a prospective study and herein our present preliminary results. METHODS: In 14
      patients with nonresectable esophageal carcinoma, the Polyflex stent was
      implanted to reduce dysphagia. The grade of dysphagia, the complications
      following intervention, and the patients' total survival time were documented
      prospectively every 4 weeks. RESULTS: The implantation of the stent was
      successful in all cases. The grade of the dysphagia was reduced from 3.0 to 0.5
      after stent implantation. One patient died during the hospital stay from a non
      stent-induced complication. Stent dislocation occurred once, and tumor overgrowth
      at the stent margins was observed twice. The mean survival time was 6.2 months,
      and the reintervention rate was 21.3%. CONCLUSION: The new Polyflex stent, which
      is based on a completely new design, can be implanted without any difficulty and
      has had very good short- and long-term results. Therefore, it is a worthy
      alternative to the metal stents in current use.

PMID- 11965463
TI  - Gasless laparoscopic cholecystectomy is not more time-consuming.
AB  - BACKGROUND: Although abdominal wall retraction is said to be advantageous in
      laparoscopic cholecystectomy (LC), many surgeons have found that, when this
      option is chosen, more time is needed to prepare for and carry out the surgical
      procedure. Our aim was to determine the time required for surgical preparation
      and operation in patients undergoing LC with carbon dioxide (CO2)
      pneumoperitoneum (CO2 PP) vs abdominal wall retraction (AWR). METHODS: We
      performed a prospective randomized study of a CO2 PP LC group (n = 19) vs an AWR
      LC group (n = 15). Demographic data were collected preoperatively. LC was
      performed with either CO2 PP (12 mmHg) or AWR (6-10 kps). Two phases were
      considered: (a) time employed to create the surgical field (phase 1) and (b)
      operating time (phase 2). The chi-square test was used to compare the medians of
      the two groups. RESULTS: The two groups were homogeneous. Phase 1 required 35 min
      in the CO2 PP group vs 25 min in the AWR group (p = 0.24). Phase 2 required 60
      min in both groups (p = 0.76). CONCLUSION: We found no statistically significant
      difference between the PP CO2 and AWR groups in either time spent to create the
      surgical field or actual operating time.

PMID- 11965464
TI  - Laparoscopic cholecystectomy causes less sleep disturbance than open abdominal
      surgery.
AB  - BACKGROUND: The aim of this study was to examine subjective sleep quality before
      and after laparoscopic vs open abdominal surgery. METHODS: Twelve patients
      undergoing laparoscopic cholecystectomy and 15 patients undergoing laparotomy
      were evaluated with the aid of a sleep questionnaire from 4 days before until 4
      weeks after surgery. RESULTS: Following laparoscopic surgery, total sleep time
      increased during the 1st week after the operation compared with preoperative
      values (p = 0.02), whereas sleep duration during weeks 2, 3, and 4 did not differ
      from the times reported preoperatively. Following laparotomy, sleep duration
      increased during the 1st, 3rd, and 4th weeks after the operation compared with
      preoperative values (p < 0.05). All patients experienced postoperative circadian
      sleep disturbance, with significantly more sleep during the daytime compared with
      preoperative values; the disturbance was present 1 week after laparoscopy and 4
      weeks after laparotomy. CONCLUSIONS: After laparotomy, total sleep time increased
      and there was a change in diurnal sleep distribution. These sleep alterations
      were less pronounced after laparoscopic cholecystectomy. Thus, sleep architecture
      was disturbed for ?4 weeks after major abdominal surgery but for only 1 week
      after laparoscopic cholecystectomy.

PMID- 11965465
TI  - Radio-guided video-assisted parathyroidectomy: a preliminary report.
AB  - BACKGROUND: The surgical management of primary hyperparathyroidism is changing
      both in terms of the extent of cervical exploration and in technique. There are
      many new mini-invasive procedures for neck surgery. We describe our preliminary
      experience with a technique that combines two mini-invasive procedures--radio
      guided and video-assisted parathyroidectomy. METHODS: Six consecutive patients
      with no recurrent or persistent primary hyperparathyroidism, no previous cervical
      operations, and no thyroid pathologies were selected to undergo radio-guided
      video-assisted parathyroidectomy. RESULTS: One case was converted. There was no
      morbidity or mortality in the postoperative period. Six parathyroids were
      removed; the histological diagnosis was adenoma in all cases. All patients were
      discharged on the 1st postoperative day. Calcium serum levels normalized in all
      cases, with only one case of transient postoperative hypocalcemia. All patients
      were normocalcemic after 6 months. CONCLUSION: Radio-guided video-assisted
      parathyroidectomy is feasible in selected patients. However, longer follow-up and
      more cases are necessary before this procedure can be applied routinely.

PMID- 11965466
TI  - Three-dimensional navigated laparoscopic ultrasonography: first experiences with
      a new minimally invasive diagnostic device.
AB  - BACKGROUND: A three-dimensional (3D) display of diagnostic imaging methods is
      technically feasible and increasingly important. However, the technical
      integration of laparoscopic ultrasound and 3D image reconstruction has not yet
      been realized. For this purpose, an electromagnetic navigation system was
      integrated into the tip of a conventional laparoscopic ultrasound probe. This
      first experience with a certified prototype of a navigated 3D laparoscopic
      ultrasound probe is reported. METHODS: Navigated 3D laparoscopic ultrasound was
      compared with the imaging data of 3D-navigated transcutaneous ultrasound and 3D
      computed tomography (CT) scan. The 3D CT scan served as the "gold standard."
      Clinical applicability, imaging quality, diagnostic potential, and accuracy in
      volumetric assessment of various well-defined hepatic lesions were analyzed.
      RESULTS: Navigated 3D laparoscopic ultrasound facilitates exact definition of
      tumor location and margins. As compared with the "gold standard" of the 3D CT
      scan, 3D laparoscopic ultrasound has a mild tendency to underestimate the volume
      of the region of interest (ROI) (D 3.1%). A comparison of 3D laparoscopy and
      transcutaneous 3D ultrasonography clearly demonstrated that the former is more
      accurate for volumetric assessment of the ROI. CONCLUSIONS: Three-dimensional
      laparoscopic ultrasound imaging with a navigated probe is technically feasible.
      The technique facilitates detailed ultrasound evaluation of laparoscopic
      procedures involving visual, in-depth, and volumetric perception of complex liver
      pathologies. Navigated 3D laparoscopic ultrasound may have the potential to
      improve the significance of laparoscopic ultrasonography, and additionally to
      become a valuable technology for planning and improving interventions guided by
      laparoscopic ultrasound.

PMID- 11965467
TI  - The impact of the surgeon's experience on the results of laparoscopic hernia
      repair.
AB  - BACKGROUND: The aim of this study was to evaluate our experience with the totally
      extraperitoneal (TEP) laparoscopic approach to hernia repair. METHODS: We
      performed a prospective study of 1227 hernia repairs using the TEP technique over
      a 7-year period. The main outcome measurements were postoperative complications,
      conversion rate, learning curve effect, surgery time, hospital stay, return to
      work, and recurrence rate. RESULTS: The mean operating time was > 60 min during
      the first 50 cases, but it fall to 32 min for the last 200 cases (p < 0.05). The
      conversion rate was 5.7% (56 patients); declining from 17% in the first 100 cases
      to 2.2% for the final 500 cases (p < 0.01). There were 79 complications (6.4%)
      and 23 recurrences (2.3%); 42% of the complications and 61% of the recurrences
      appeared in the first 100 cases (p < 0.05). CONCLUSION: This study shows that
      postoperative complications, conversion rate, operating time, and recurrences are
      all substantially reduced as the surgeon's experience increases. Thus, once the
      learning curve is surpassed, TEP repair represents a good alternative to open
      techniques.

PMID- 11965468
TI  - Optimal mesh size for endoscopic inguinal hernia repair: a study in a porcine
      model.
AB  - BACKGROUND: Although the recurrence rate for endoscopic herniorraphy is low (0
      3%), it can still be improved. In addition to using an expert technique that will
      minimize the risk of recurrence, it is essential that the mesh be large enough to
      cover the hernial defect adequately. To gain an impression of the optimal mesh
      size for such repairs, we performed an experimental study in a porcine model.
      METHODS: To mimic inguinal hernial defects, circular holes of different diameters
      were cut in the pigs' abdominal walls after the peritoneum was lifted from the
      transverse fascia. The abdominal walls were positioned in a hermetically sealed
      chamber in which air pressure was applied to replicate intraabdominal pressure.
      Measurements were obtained to relate the protrusion of the mesh to the following
      three variables: intraabdominal pressure, defect size, and mesh overlap over the
      defect after positioning of the mesh between the abdominal wall and the
      peritoneum. RESULTS: Mesh protrusion increased as defect size and intraabdominal
      pressure increased. Mesh protrusion decreased as overlap of the mesh over the
      defect increased. Protrusion was found to level off when the mesh overlapped the
      defect by 3 cm and adequate positioning of the mesh was maintained. CONCLUSION:
      Recurrences after endoscopic inguinal hernia repair due to inadequate mesh size
      and mesh protrusion can be reduced by using a mesh that overlaps the defect by >
      or = 3 cm.

PMID- 11965469
TI  - Optimal positive end-expiratory pressure (PEEP) settings in differential lung
      ventilation during simultaneous unilateral pneumothorax and laparoscopy: an
      experimental study in pigs.
AB  - BACKGROUND: A combined thoraco-laparoscopic technique for esophageal resection is
      technically possible, but it requires special attention to ventilation. The
      positive insufflation pressure normally used in laparoscopy will, when
      communication between thorax and abdomen is established, create a pneumothorax.
      METHODS: We performed an experimental study of differential lung ventilation with
      different levels of positive end-expiratory pressure (PEEP) settings during
      thoraco-laparoscopy in anesthetized pigs. RESULTS: Positive pressure insufflation
      of carbon dioxide (CO2) resulted in elevated pulmonary capillary wedge pressure,
      hypercarbia, and respiratory acidosis. Hypoxemia, however, developed only at
      lower settings of PEEP. Heart rate, mean arterial pressure, and cardiac output
      remained relatively stable. CONCLUSION: Pneumopleuroperitoneum under positive CO2
      insufflation pressure had adverse effects on blood gases. Hypercarbia,
      respiratory acidosis, and hypoxemia were early manifestations that occurred even
      in the presence of hemodynamic stability. The application of PEEP equal to or
      above CO2 insufflation pressure improved blood gases; in particular, the hypoxia
      could be avoided. No beneficial effects of differential lung ventilation were
      documented.

PMID- 11965470
TI  - Kinetics of cytokines and PMN-E in thoracoscopic esophagectomy.
AB  - BACKGROUND: Perioperative increases in the levels of cytokines and
      polymorphonuclear leukocyte elastase (PMN-E) have been shown to be related to
      degree of surgical trauma. METHODS: We measured the changes in levels of
      interleukin-6 (IL-6), interleukin-8 (IL-8), and PMN-E in the perioperative period
      in patients undergoing thoracoscopic esophagectomy (n = 15) and conventional
      transthoracic esophagectomy (n = 15) for thoracic esophageal cancer. RESULTS:
      Both IL-6 and IL-8 increased markedly immediately after transthoracic
      esophagectomy and thereafter, but only a slight increase was observed after the
      thoracoscopic procedure (IL-6: p = 0.047; IL-8: p = 0.03). A difference was also
      seen in the pattern of changes in PMN-E. Levels of PMN-E increased immediately
      after transthoracic esophagectomy and continued to be high up to the 3rd
      postoperative day, but they remained low after the thoracoscopic procedure and
      showed no increase (p <lt; 0.01). CONCLUSION: These results suggest that,
      compared with transthoracic esophagectomy, thoracoscopic esophagectomy results in
      less production of cytokines and PMN-E and thus causes less surgical trauma.

PMID- 11965471
TI  - Pancreatic injury: an unusual complication of laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy is a popular method for managing symptomatic
      gallstone disease. Decreased morbidity and mortality rates make this procedure an
      attractive alternative to conventional cholecystectomy. However, unusual
      complications still occur. We report a case of pancreatic injury that occurred
      during laparoscopic cholecystectomy. The case was complicated with posttraumatic
      pancreatic inflammation and bowel necrosis.

PMID- 11965472
TI  - Laparoscopic repair of traumatic perforation of the urinary bladder.
AB  - Laparoscopy as a diagnostic modality in trauma has been reported. However,
      therapeutic laparoscopy for trauma remains a controversial subject. We present a
      case of laparoscopic repair of a traumatic bladder rupture. A 25-year-old man was
      brought to the emergency room after a head-on collision. Physical examination was
      unremarkable with the exception of gross hematuria upon insertion of a urinary
      catheter. Computed tomography scan of the abdomen demonstrated a small amount of
      free intraperitoneal fluid. An anteroposterior cystogram was obtained which
      showed no intraperitoneal or extraperitoneal leak. Repeat examinations of the
      abdomen revealed a mild tenderness in the lower abdomen. Because of the presence
      of unexplained free intraperitoneal fluid and equivocal signs of peritoneal
      irritation, exploratory laparoscopy was performed. Three 5-mm ports and a 5-mm
      laparoscope were used. Laparoscopic examination of the abdomen revealed a 4-cm
      rupture at the dome of the bladder. The laceration was sutured in two layers
      using an intracorporeal technique. The patient was discharged on the second
      postoperative day with indwelling urinary catheter. Eight days after the
      operation, a repeated cystogram revealed no evidence of leak. We believe that
      laparoscopic exploration for trauma in hemodynamically stable patients is
      feasible. The repair of simple intraabdominal injuries such as bladder rupture
      can be safely performed.

PMID- 11965473
TI  - Gastric remnant carcinoma: reevaluation of screening endoscopy.
AB  - A 67-year-old male presented with complaints of chronic postprandial pain in the
      epigastric region. The patient had undergone a vagotomy, antrectomy, and loop
      gastrojejunostomy for peptic ulcer disease 25 years prior. Abdominal computed
      tomography (CT) revealed markedly thickened walls of the gastric remnant with
      infiltration of the adjacent fat planes. An esophagogastroscopy demonstrated
      erythematous, friable remnant mucosa. Gastric biopsies revealed invasive
      adenocarcinoma. At laparotomy a large tumor mass involving the gastric remnant
      and the antecolic loop gastrojejunostomy was identified. Further exploration
      revealed a firm nodule in the left lobe of the liver and several small nodules on
      the diaphragm and the lesser omentum. Biopsies confirmed metastatic
      adenocarcinoma at all sites. Curative resection was abandoned. Gastric remnant
      carcinoma (GRC) typically presents more than 20 years after resection for peptic
      ulcer disease and has a history of poor survival rates. With increased use of
      diagnostic endoscopy, GRC has been detected at earlier stages. Recent cohort
      studies demonstrate that GRC has similar survival rates after stage
      stratification when compared with primary proximal gastric carcinoma. The
      increased incidence of GRC in later decades (>20 years) after operation in
      conjunction with decreasing numbers of patients suggests that screening endoscopy
      should be considered on a 2- to 5-year basis in this population.

PMID- 11965474
TI  - Endoscopic treatment of benign esophageal tumors: case report of three patients.
AB  - Benign esophageal tumors are rare. Enucleation of the tumor is considered when
      the patient reports problems. The traditional approach is to use thoracotomy or
      laparotomy if the tumor is located in the distal esophagus. The use of minimally
      invasive techniques permits enucleation with all the concomitant advantages. Our
      experience with the minimally invasive management of three benign esophageal
      tumors is described. The methods and results of preoperative studies are
      reported. The surgical technique is described. Two patients could be managed
      using thoracoscopy, and one patient required conversion to laparoscopy. All the
      patients had complete and quick recoveries.

PMID- 11965476
TI  - Laparoscopic enucleation of giant liver hemangioma.
AB  - The cavernous hemangioma is the most common benign tumor of the liver. It usually
      becomes symptomatic as it reaches a certain size. A 49-year-old man was admitted
      with a 1-year history of epigastric pain, which was not relieved by regular
      analgesic intake, and nausea. The results of physical examination, routine
      laboratory tests, and upper gastrointestinal tract endoscopy were normal.
      Ultrasonography showed a 10-cm mass in the left hepatic lobe. Magnetic resonance
      imaging (MRI) showed a 90-mm hemangioma at left hepatic lobe. Selective celiac
      arteriogram was performed, and polyvinyl alcohol particles were used as an
      embolizing agent. After the embolization, the patient underwent laparoscopic
      enucleation of the liver hemangioma. No blood transfusion was needed during the
      operation. The operative time was 75 min. The patient was allowed to take a clear
      liquid diet on the postoperative day 1. The postoperative course of the patient
      was uneventful, and he was discharged on the postoperative day 2. Enucleation is
      the best surgical technique for the management of symptomatic giant hemangiomas.
      It can be performed with no mortality or morbidity, with preservation of all
      normal liver parenchyma. Enucleation also has been associated with significantly
      fewer intraabdominal complications than anatomic resection. The laparoscopic
      approach for enucleation requires patience and careful dissection to prevent
      bleeding. In conclusion, laparoscopic enucleation of hemangiomas is safe and easy
      to perform in selected cases.

PMID- 11965475
TI  - Portal vein thrombosis following laparoscopic splenectomy for beta-thalassemia: a
      case study.
AB  - Portal vein thrombosis is a rare but well-recognized complication of splenectomy.
      We present the case of a 31-year-old woman with transfusion-dependent b
      thalassemia who underwent a laparoscopic splenectomy to reduce her transfusion
      requirements. Postoperatively, she developed portal vein thrombosis, diagnosed by
      abdominal CT scanning on postoperative day 4. After being treated with
      anticoagulation and antibiotic therapy, she obtained prompt resolution of her
      symptoms. This report summarizes the first reported incidence of portal vein
      thrombosis following laparoscopic splenectomy and presents the current theories
      regarding the etiology and treatment of postsplenectomy portal vein thrombosis.

PMID- 11965477
TI  - Use of endoscopic retrograde cholangiopancreatography to dislodge clip
      impingement on the common hepatic duct.
AB  - Despite advances in technical skill, bile duct injury during laparoscopic
      cholecystectomy is not an uncommon complication. We describe a technique of using
      ERCP, sphincterotomy, and balloon dilatation to dislodge clip impingement on the
      common hepatic duct after laparoscopic cholecystectomy.

PMID- 11965478
TI  - Cecal herniation through the foramen of Winslow after laparoscopic Nissen
      fundoplication.
AB  - Laparoscopic Nissen fundoplication is the treatment of choice for medically
      refractive gastroesophageal reflux disease. Cecal herniation is an exceedingly
      rare complication of this procedure. We report the case of a 51-year-old woman
      who presented 2 months after a successful laparoscopic Nissen fundoplication with
      heartburn and epigastric pain that radiated to her back. Abdominal films showed
      an air-filled loop in the left upper quadrant. At surgery, the patient had a
      redundant loop of cecum, which had herniated through the foramen of Winslow over
      the stomach and was positioned beneath the left hemidiaphragm. The cecum was not
      ischemic. A right hemicolectomy was performed to prevent recurrence. The patient
      recovered fully and has had no further problems. This is the first report of such
      a case.

PMID- 11965479
TI  - Subfascial endoscopic perforator vein surgery (SEPS) using the ultrasonic
      scalpel.
AB  - Subfascial endoscopic perforator vein surgery (SEPS) was recently introduced as a
      minimally invasive method to ligate incompetent perforating veins in patients
      with severe chronic venous insufficiency of the lower extremities. Herein we
      describe a technique in which we used a 5-mm ultrasonic scalpel for the
      transection of perforating veins in 16 SEPS performed in 14 patients. The use of
      the ultrasonic scalpel allowed for the precise coagulation and transection of the
      perforator vein with hemostasis, while avoiding the use of metal clips. Our
      initial results showed that the technique was feasible with minimal morbidity. We
      recommend the use of the ultrasonic scalpel as an alternative tool to transect
      perforating veins in SEPS.

PMID- 11965480
TI  - A balanced approach to choledocholithiasis.

PMID- 11965482
TI  - Splenosis after laparoscopic splenectomy.

PMID- 11965484
TI  - Minimally invasive surgery and its role in space exploration.

PMID- 11965485
TI  - The meaning of death.

PMID- 11965486
TI  - Apoptosis timeline.

PMID- 11965487
TI  - Infection and the origins of apoptosis.

PMID- 11965488
TI  - Alice in caspase land. A phylogenetic analysis of caspases from worm to man.

PMID- 11965489
TI  - Jekyll and Hyde; changing places, changing faces.

PMID- 11965490
TI  - Suicide determines self.

PMID- 11965491
TI  - On the origin, evolution, and nature of programmed cell death: a timeline of four
      billion years.
AB  - Programmed cell death is a genetically regulated process of cell suicide that is
      central to the development, homeostasis and integrity of multicellular organisms.
      Conversely, the dysregulation of mechanisms controlling cell suicide plays a role
      in the pathogenesis of a wide range of diseases. While great progress has been
      achieved in the unveiling of the molecular mechanisms of programmed cell death, a
      new level of complexity, with important therapeutic implications, has begun to
      emerge, suggesting (i) that several different self-destruction pathways may exist
      and operate in parallel in our cells, and (ii) that molecular effectors of cell
      suicide may also perform other functions unrelated to cell death induction and
      crucial to cell survival. In this review, I will argue that this new level of
      complexity, implying that there may be no such thing as a 'bona fide' genetic
      death program in our cells, might be better understood when considered in an
      evolutionary context. And a new view of the regulated cell suicide pathways
      emerges when one attempts to ask the question of when and how they may have
      become selected during evolution, at the level of ancestral single-celled
      organisms.

PMID- 11965492
TI  - Origin and evolution of eukaryotic apoptosis: the bacterial connection.
AB  - The availability of numerous complete genome sequences of prokaryotes and several
      eukaryotic genome sequences provides for new insights into the origin of unique
      functional systems of the eukaryotes. Several key enzymes of the apoptotic
      machinery, including the paracaspase and metacaspase families of the caspase-like
      protease superfamily, apoptotic ATPases and NACHT family NTPases, and
      mitochondrial HtrA-like proteases, have diverse homologs in bacteria, but not in
      archaea. Phylogenetic analysis strongly suggests a mitochondrial origin for
      metacaspases and the HtrA-like proteases, whereas acquisition from Actinomycetes
      appears to be the most likely scenario for AP-ATPases. The homologs of apoptotic
      proteins are particularly abundant and diverse in bacteria that undergo complex
      development, such as Actinomycetes, Cyanobacteria and alpha-proteobacteria, the
      latter being progenitors of the mitochondria. In these bacteria, the apoptosis
      related domains typically form multidomain proteins, which are known or inferred
      to participate in signal transduction and regulation of gene expression. Some of
      these bacterial multidomain proteins contain fusions between apoptosis-related
      domains, such as AP-ATPase fused with a metacaspase or a TIR domain. Thus,
      bacterial homologs of eukaryotic apoptotic machinery components might
      functionally and physically interact with each other as parts of signaling
      pathways that remain to be investigated. An emerging scenario of the origin of
      the eukaryotic apoptotic system involves acquisition of several central apoptotic
      effectors as a consequence of mitochondrial endosymbiosis and probably also as a
      result of subsequent, additional horizontal gene transfer events, which was
      followed by recruitment of newly emerging eukaryotic domains as adaptors.

PMID- 11965493
TI  - Bag1 is a regulator and marker of neuronal differentiation.
AB  - Bag 1 acts as a co-chaperone for Hsp70/Hsc70. We report here that stable over
      expression of Bag1 in immortalized neuronal CSM14.1 cells prevents death
      following serum deprivation. Bag1 over-expression slowed the proliferative rate
      of CSM14.1 cells, resulted in increased levels of phospo-MAP kinases and
      accelerated neuronal differentiation. Immunocytochemistry revealed mostly nuclear
      localization of Bag1 protein in these cells. However, during differentiation in
      vitro, Bag1 protein shifted from predominantly nuclear to mostly cytosolic in
      CSM14.1 cells. To explore in vivo parallels of these findings, we investigated
      Bag1 expression in the developing mouse nervous system using immunohistochemical
      methods. Early in brain development, Bag1 was found in nuclei of neuronal
      precursor cells, whereas cytosolic Bag1 staining was observed mainly after
      completion of neuronal precursor migration and differentiation. Taken together,
      these findings raise the possibility that the Bag1 protein is expressed early in
      neurogenesis in vivo and is capable of modulating neuronal cell survival and
      differentiation at least in part from a nuclear location.

PMID- 11965494
TI  - PTEN augments staurosporine-induced apoptosis in PTEN-null Ishikawa cells by
      downregulating PI3K/Akt signaling pathway.
AB  - Staurosporine is a potent apoptosis inducer, but its mechanism remains to be
      clarified. We investigated the involvement of PTEN in staurosporine-induced
      apoptosis. Ishikawa cells, from an endometrial carcinoma cell line, expressed a
      high amount of PTEN mRNA but did not express the PTEN protein because of protein
      truncations. We isolated clones expressing the steady-state level of the PTEN
      protein from PTEN-null Ishikawa cells by transfection. The obtained clones showed
      reduced proliferative activity and reduced anchorage-independent cell growth with
      the augmented p27(Kip1). These cell lines were sensitized to apoptosis by
      staurosporine. A low concentration of UCN-01 did not affect apoptosis, but a high
      concentration augmented apoptosis in the PTEN-expressing clone. Alpha-sphingosine
      and H-7 did not affect apoptosis in these cell lines. PI3K inhibition augmented
      staurosporine-induced apoptosis in the parental cell line, but not in the PTEN
      expressing clone. In the clone, phosho-Akt/PKB and phospho-Bad (Ser-136) were
      downregulated. Staurosporine reduced the levels of phospho-Akt/PKB and phospho
      Bad (Ser-136) in all the cell lines, but the reduction was most significant in
      the PTEN-expressing clone. These results suggest that inhibition of the
      PI3K/Akt/PKB signaling pathway might be associated with staurosporine-induced
      apoptosis in Ishikawa cells.

PMID- 11965495
TI  - Cyclin dependent kinase 5 and its interacting proteins in cell death induced in
      vivo by cyclophosphamide in developing mouse embryos.
AB  - Activation or inactivation of members of the cyclin-dependent kinase family is
      important during cell cycle progression. However, Cdk5, a member of this family
      that was originally identified because of its high structural homology to Cdc2,
      is activated during cell differentiation and cell death but not during cell cycle
      progression. We previously demonstrated a correlation between the up-regulation
      of Cdk5 protein and kinase activity and cell death during development and
      pathogenesis. We report here that cyclophosphamide (CP) induces massive apoptotic
      cell death in mouse embryos and that Cdk5 is expressed in apoptotic cells
      displaying fragmented DNA. During CP-induced cell death, Cdk5 protein expression
      is substantially increased as detected by immunohistochemistry but not by Western
      blot, while its mRNA level remains the same as control, and its kinase activity
      is markedly elevated. The up-regulation of Cdk5 during CP-induced cell death is
      not due to de novo protein synthesis. We also examined p35, a regulatory protein
      of Cdk5 in neuronal differentiation. Using a yeast two-hybrid system, we isolated
      p35, a neuronal differentiation specific protein, as a protein that interacts
      with Cdk5 in CP-treated embryos. p35 mRNA level does not change, but the protein
      expression of p25, a truncated form of p35, is elevated during cell death in
      vivo, as established here, as well as during cell death in vitro. Our results
      suggest a role for Cdk5 and its regulatory proteins during CP induced cell death.
      These results further support the view that Cdk5 and its regulation may be key
      players in the execution of cell death regardless of how the cell dies, whether
      through biological mechanisms, disease states such as Alzheimer's disease, or
      induction by CP.

PMID- 11965496
TI  - Genetic polymorphisms of Fas (CD95) and FasL (CD178) in human longevity: studies
      on centenarians.
AB  - Apoptosis plays a crucial role in immunosenescence, as also evidenced by the
      increased expression of Fas in lymphocytes from aged people. However, little is
      known about the genetic regulation of Fas and its ligand, FasL. We have studied
      their polymorphisms in 50 centenarians and 86 young donors living in Northern
      Italy. The first Fas polymorphism, at position -670, has in Caucasian a
      heterozigosity of 51%; the second, at -1377 position, has the wild type allele
      (G) with a very high frequency (83%) respect to the mutant allele. Genotype and
      allele distribution for both polymorphisms were similar in controls and
      centenarians. Similar results were found as far as two FasL polymorphisms (IVS2nt
      124 and IVS3nt169) are concerned. On the whole, our data suggest that Fas and
      FasL polymorphisms, as well as their haplotypes, are unlikely to be associated
      with successful human longevity.

PMID- 11965497
TI  - Death effector domain-containing proteins DEDD and FLAME-3 form nuclear complexes
      with the TFIIIC102 subunit of human transcription factor IIIC.
AB  - Death effector domain-containing proteins are involved in important cellular
      processes such as death-receptor induced apoptosis, NF-kappaB activation and ERK
      activation. Here we report the identification of a novel nuclear DED-containing
      protein, FLAME-3. FLAME-3 shares significant sequence (46.6% identical) and
      structural homology to another DED-containing protein, DEDD. FLAME-3 interacts
      with DEDD and c-FLIP (FLAME-1) but not with the other DED-containing proteins
      FADD, caspase-8 or caspase-10. FLAME-3 translocates to, and sequesters c-FLIP in
      the nucleus upon overexpression in human cell lines. Using the yeast two-hybrid
      system to identify DEDD-interacting proteins, the TFIIIC102 subunit of human
      transcription factor TFIIIC was identified as a DEDD- and FLAME-3-specific
      interacting protein. Co-expression of either DEDD or FLAME-3 with hTFIIIC102 in
      MCF-7 cells induces the translocation from the cytoplasm and sequestration of
      hTFIIIC102 in the nucleus, indicating that DEDD and FLAME-3 form strong
      heterocomplexes with hTFIIIC102 and might be important regulators of the activity
      of the hTFIIIC transcriptional complex. Consistent with this, overexpression of
      DEDD or FLAME-3 in 293 cells inhibited the expression of a luciferase-reporter
      gene under the control of the NF-kappaB promoter. Our data provide the first
      direct evidence for the involvement of DED-containing proteins in the regulation
      of components of the general transcription machinery in the nucleus.

PMID- 11965498
TI  - Downregulation of ERK2 is essential for the inhibition of radiation-induced cell
      death in HSP25 overexpressed L929 cells.
AB  - We previously reported that overexpression of HSP25 delayed cell growth,
      increased the level of p21(waf), reduced the levels of cyclin D1, cyclin A and
      cdc2, and induced radioresistance in L929 cells. In this study, we demonstrated
      that HSP25 induced-radioresistance was abolished by transfection with plasmids
      containing antisense hsp25 cDNA. Extracellular regulated kinase (ERK) and MAP
      kinase/ERK kinase (MEK) expressions as well as their activation (phospho-forms)
      were inhibited by hsp25 overexpression. Furthermore, when control vector
      transfected cells were treated with PD98059, MEK inhibitor, they became resistant
      to radiation, suggesting that inhibition of ERK1/2 activities was essential for
      radioresistance in L929 cells. To confirm the relationship between ERK1/2 and
      hsp25-mediated radioresistance, ERK1 or ERK2 cDNA was transiently transfected
      into the hsp25 overexpressed cells and their radioresistance was examined. HSP25
      mediated radioresistance was abolished by overexpression of ERK2, but not by
      overexpression of ERK1. Alteration of cell cycle distribution and cell cycle
      related protein expressions (cyclin D, cyclin A and cdc2) by hsp25 overexpression
      were also recovered by ERK2 cDNA transfection. Increase in Bcl-2 protein by hsp25
      gene transfection was also reduced by subsequent ERK2 cDNA-transfection. Taken
      together, these results suggest that downregulation of ERK2 is essential for the
      inhibition of radiation-induced cell death in HSP25 overexpressed cells.

PMID- 11965499
TI  - Clearance of apoptotic beta-cells is reduced in neonatal autoimmune diabetes
      prone rats.
AB  - The kinetics of beta-cell death in neonatal diabetes-prone (BBdp) and diabetes
      resistant (BBdr) BioBreeding rats was investigated using both direct
      (histochemical) and indirect (mathematical modelling) techniques. In both BBdp
      and BBdr rats, the incidence of TUNEL positive beta-cells increased until 10 days
      of age before declining. The number of apoptotic beta-cells was significantly
      higher in BBdp as compared to BBdr neonates from birth until 20 days of age
      (P<0.05). Using a mathematical model applied to the time course of beta-cell mass
      and replication rate, a wave of net beta-cell loss was detected between 10 and 20
      days of age in both strains. In contrast to the observed difference in the
      incidence of TUNEL positive beta-cells, with the model-based approach we found no
      difference in the rate of beta-cell apoptosis between BBdp and BBdr rats prior to
      weaning. As the number of apoptotic cells present in a tissue depends on the rate
      at which cells die and the rate at which the apoptotic cell debris is cleared, we
      compared in vitro phagocytosis of apoptotic thymocytes by peritoneal macrophages
      from 2-week-old BBdp and BBdr rats. Macrophages from BBdp neonates engulfed
      significantly less apoptotic cells as compared to BBdr neonates (P<0.0005). Taken
      together, these findings suggest that there is impaired clearance of apoptotic
      beta-cells in diabetes-prone BB rats during the neonatal period.

PMID- 11965500
TI  - Endoplasmic reticulum stress-induced cell death requires mitochondrial membrane
      permeabilization.

PMID- 11965501
TI  - 'Centennial' Nobel Conference on apoptosis and human disease.

PMID- 11965502
TI  - The anemia of vitamin A deficiency: epidemiology and pathogenesis.
AB  - OBJECTIVE: To gain insight into vitamin A deficiency as a cause of anemia.
      METHODS: Comprehensive review of the scientific literature. RESULTS: Although
      vitamin A deficiency is recognized to cause anemia, 'vitamin A deficiency anemia'
      lacks complete characterization as a distinct clinical entity. Vitamin A appears
      to be involved in the pathogenesis of anemia through diverse biological
      mechanisms, such as the enhancement of growth and differentiation of erythrocyte
      progenitor cells, potentiation of immunity to infection and reduction of the
      anemia of infection, and mobilization of iron stores from tissues.
      Epidemiological surveys show that the prevalence of anemia is high in populations
      affected by vitamin A deficiency in developing countries. Improvement of vitamin
      A status has generally been shown to reduce anemia, but the actual public health
      impact on anemia is unclear. CONCLUSIONS: Further work is needed to elucidate the
      biological mechanisms by which vitamin A causes anemia. The inclusion of anemia
      as an outcome measure in future micronutrient intervention studies should help
      provide further insight into the anemia of vitamin A deficiency.

PMID- 11965503
TI  - Total daily energy expenditure in wasted chronic obstructive pulmonary disease
      patients.
AB  - OBJECTIVES: To investigate total daily energy expenditure in chronic obstructive
      pulmonary disease (COPD) patients during a rehabilitation programme. DESIGN:
      Observational study involving a case and a control group. SUBJECTS: Ten COPD
      patients (six with body mass index (BMI) <18.5 kg/m(2) and four with BMI >18.5
      kg/m(2)) were evaluated for their energy expenditure profile. Four additional
      healthy age-matched volunteers were also included for methodology evaluation.
      INTERVENTIONS: Measurements of total daily energy expenditure (TEE), resting
      energy expenditure (REE) and diet-induced thermogenesis (DIT) and energy intake
      were undertaken by indirect calorimetry and bicarbonate-urea methods and dietary
      records. RESULTS: REE in COPD patients was not significantly different from that
      predicted by the Harris-Benedict equation. Before the exercise day the mean TEE
      was 1508 kcal/day and physical activity level (PAL as calculated by TEE/REE) was
      1.52. On the exercise day the TEE increased to 1568 kcal/day and PAL was 1.60,
      but neither of these changes were significant. The energy cost of increased
      physical activity during rehabilitation exercise was estimated to be 191
      kcal/day. No significant change was found in DIT between the two patient groups.
      However, overall energy balances were found to be negative (-363 kcal/day).
      CONCLUSION: The rehabilitation programme did not cause a significant energy
      demand in COPD patients. TEE in COPD patients was not greater than in free-living
      healthy subjects. Patients, who were underweight, did not have a higher TEE than
      patients with normal weight. This suggested that malnutrition in COPD patients
      was not due to an increased energy expenditure. On the other hand, a significant
      negative energy balance due to insufficient energy intake was found in seven out
      of 10 patients.

PMID- 11965504
TI  - Energy metabolism in humans at a lowered ambient temperature.
AB  - OBJECTIVE: Assessment of the effect of a lowered ambient temperature, ie 16
      degrees C (61 degrees F), compared to 22 degrees C (72 degrees F), on energy
      intake (EI), energy expenditure (EE) and respiratory quotient (RQ) in men.
      DESIGN: Randomized within-subject design in which subjects stayed in a
      respiration chamber three times for 60 h each, once at 22 degrees C, and twice at
      16 degrees C, wearing standardized clothing, executing a standardized daily
      activities protocol, and were fed in energy balance (EBI): no significant
      difference between EE and EI over 24 h). During the last 24 h at 22 degrees C,
      and once during the last 24 h at 16 degrees C, they were fed ad libitum.
      SUBJECTS: Nine dietary unrestrained male subjects (ages 24+/-5 y, body mass index
      (BMI) 22.7+/-2.1 kg/m(2), body weight 76.2+/-9.4 kg, height 1.83+/-0.06 m, 18+/
      5% body fat). RESULTS: At 16 degrees C (EB), EE (total 24 h EE) was increased to
      12.9+/-2.0 MJ/day as compared to 12.2+/-2.2 MJ/day at 22 degrees C (P<0.01). The
      increase was due to increases in sleeping metabolic rate (SMR; the lowest EE
      during three consecutive hours with hardly any movements as indicated by radar):
      7.6+/-0.7 vs 7.2+/-0.7 MJ/day (P<0.05) and diet-induced thermogenesis (DIT; EE
      SMR, when activity induced energy expenditure as indicated by radar=0): 1.7+/-0.4
      vs 1.0+/-0.4 MJ/day (P<0.01). Physical activity level (PAL; EE/SMR) was 1.63
      1.68. At 16 degrees C compared to at 22 degrees C, rectal, proximal and distal
      skin temperatures had decreased (P<0.01). RQ was not different between the two
      ambient temperature situations. During ad libitum feeding, subjects overate by
      32+/-12% (at 22 degrees C) and by 34+/-14% (at 16 degrees C). Under these
      circumstances, the decrease of rectal temperature at 16 degrees C was attenuated,
      and inversely related to percentage overeating (r(2)=0.7; P<0.01). CONCLUSION: We
      conclude that at 16 degrees C, compared to 22 degrees C, energy metabolism was
      increased, due to increases in SMR and DIT. Overeating under ad libitum
      circumstances at 16 degrees C attenuated the decrease in rectal core body
      temperature.

PMID- 11965505
TI  - Reduction of visceral adipose tissue during weight loss.
AB  - OBJECTIVE: The aims of the present study were to retrospectively: (1) compare how
      weight loss affects the reduction of adipose tissue from three different sites
      between men and women; and (2) to verify whether gender differences in the
      reduction of adipose tissue are influenced by changes in fat mass (FM) and
      initial levels of fat in different compartments. DESIGN: Double-blind randomized
      treatment with fenfluramine once daily coupled to a non-macronutrient specific
      energy restriction. SUBJECTS: Seventeen obese men (age 43.9+/-1.5 and body mass
      index (BMI) 34.3+/-0.7) and 17 obese women (age 41.2+/-1.2 and BMI 35.7+/-0.6).
      INTERVENTIONS: Subjects were given fenfluramine (60 mg) or placebo once daily and
      were also subjected to a non-macronurient specific energy restriction of -2.9
      MJ/day (-700 kcal/day) for 15 weeks. RESULTS: Body weight, FM, fat-free mass
      (FFM), waist circumference, BMI, as well as visceral (VAT), subcutaneous
      abdominal (SAT) and thigh (TAT) adipose tissue were all significantly reduced.
      Men lost significantly more VAT (-41.6%) than SAT (-22.5%), or than TAT (-20.5%)
      while no site difference in fat loss was observed in women when changes were
      calculated as a percentage of initial levels. Men lost about twice as much fat
      from the VAT compartment than did women (P<0.05), even after having considered
      changes in FM as a potential covariate. In absolute values, TAT was reduced to a
      lesser extent in men than in women. However, when initial levels of respective
      fat depots were also taken into account, gender differences in VAT and TAT loss
      were no longer statistically significant. CONCLUSION: These results suggest that
      gender differences in VAT reduction during weight loss are independent of changes
      in FM. However, once initial levels of VAT are also taken into account, gender
      differences in the reduction of this tissue during weight loss are no longer
      apparent.

PMID- 11965506
TI  - Nutritional status of healthy elderly persons living in Dordogne, France, and
      relation with mortality and cognitive or functional decline.
AB  - OBJECTIVE: Description of the nutritional status of healthy elderly people and
      investigation of its longitudinal relationship with mortality and cognitive or
      functional decline. DESIGN: Longitudinal study. SETTING: In Dordogne, France.
      SUBJECTS: A total of 169 French elderly community dwellers aged 68 y and older
      from in the PAQUID (Personnes Agees QUID) study were included. Dietary intake was
      assessed by a 3 day food record and a dietary history. Self-reported weight and
      height were used to calculate the body mass index (BMI, kg/m(2)). Mortality,
      activities of daily living (ADL), instrumental activities of daily living (IADL)
      and the Mini Mental State Examination (MMSE) were measured at 5 y follow-up.
      RESULTS: Nutritional intake and BMI vary according to age and sex. Men generally
      have a higher nutritional intake than women. Intake decreases with age especially
      in men. Among the 169 subjects, 22 died. When analyzed by logistic regression,
      there was no relation between markers of risk of poor nutrition and mortality but
      a BMI greater or equal 27 at baseline was associated with a increased risk of 5 y
      mortality (OR=6.27, 95% CI 1.29-30.37) adjusted for sex and age. With regard to
      cognitive decline, subjects with a BMI greater or equal than 23 kg/m(2) had 3.6
      times lower chance of presenting a decline in the subsequent 5 y adjusted by age
      and sex (OR=0.28, 95%, CI 0.09-0.90). BMI ranging between 23 and 27 was
      associated with a significantly decreased risk of IADL disability (OR=0.31, 95%
      CI 0.10-0.93) in multivariate analyses. CONCLUSION: In apparently healthy elderly
      people a BMI ranging between 23 and 27 is associated with lower risks of
      functional and cognitive declines in the subsequent 5 y.

PMID- 11965507
TI  - Dietary intakes and vitamin status of a sample of homeless people in Paris.
AB  - OBJECTIVE: To determine nutritional intake and vitamin status in a sample of
      homeless people who had been on the streets of Paris for more than 2 y. DESIGN:
      The nutritional status was evaluated by a 24 h recall questionnaire and by assay
      of circulating levels of vitamins A, B1, B6, B12, C and E. SETTING: The study was
      conducted in four accommodation centres of the SAMU Social of Paris (CHUSI units)
      from July 1999 to May 2000. SUBJECTS: A total of 329 homeless people were
      interviewed. Only 87 subjects, aged 26-76 y, were recruited based on seven
      selection criteria (over 18 y old, being homeless for more than 2 y, interviewed
      before taking a meal in the CHUSI units, good understanding of French, in a calm
      state, not coming from hospital or another CHUSI units, without any acute
      condition that might affect usual dietary habits), and completed the dietary
      questionnaire. Out of these 87, 71 agreed to blood sampling. RESULTS: In all 84%
      of the subjects declared that they drank alcoholic beverages regularly (175+/-167
      g/day of alcohol), and 75.5% of the subjects also declared that they smoked. The
      mean total energy intake was 2111+/-1482 kcal/day for the men (8823.98+/-6194.76
      kJ/day) and 1523+/-531 kcal/day for the women (6366.14+/-2219.58 kJ/day). Alcohol
      accounted for 44+/-30% and 19+/-17% of the total energy intakes (TEI) for the men
      and women, respectively. Proteins, lipids and carbohydrates accounted for 21+/-9,
      23+/-14 and 57+/-16%, respectively, of the energy intake without alcohol for men,
      and 15+/-5, 22+/-11 and 62+/-14% EIWA for women. For all micronutrients, except
      for iron in the men, more than 50% of the population studied had intakes below
      the French recommendations for the adult population. All the women had calcium,
      vitamin E and vitamin B1 intakes below the recommendations for French women (900,
      12 and 1.3 mg/day, respectively) in the general population. For the men, 98.7,
      96.1 and 93.5% of the subjects had vitamin E, B1 and C intakes below the
      recommendations for French males in the general population (12, 1.5 and 80
      mg/day, respectively). It is of note that subjects who ate in the CHUSI units
      more than once a day per week had significantly (P=0.018) higher intakes of
      vitamin C (27+/-38 mg/day) than did the subjects who ate in the CHUSI units less
      than once a day (8+/-12 mg/day). Measurement of serum vitamin levels demonstrated
      a deficiency in 95% of the subjects, mainly for vitamin C. The mean concentration
      in serum was 16+/-8 micromol/l, although 72% of the subjects had levels of 6
      micromol/l. In contrast, 50.7, 42.2 and 35.2% of the subjects had high levels of
      vitamin B6, B12 and B1, respectively (100 nmol/l, 420 pmol/l and 40 micromol/l).
      CONCLUSION: Alcohol takes a high place in the diet of these homeless people.
      Although the total energy intake was too low, macronutrient intakes seem to be
      satisfactory in quality (well-balanced). However, calcium and vitamin C intakes
      were too low, and these deficiencies favour the development of disease (scurvy,
      asthenia, ecchymosis), in addition to alcohol-linked disease. Furthermore, the
      overexposure to vitamin B6, among the other B vitamins, is a matter of concern
      since it has been shown to be toxic in high doses.

PMID- 11965508
TI  - Effect of vitamin A administered at Expanded Program on Immunization contacts on
      antibody response to oral polio vaccine.
AB  - OBJECTIVE: Vitamin A supplementation to mothers in the postpartum period and to
      their infants at routine immunization contacts is being considered to reduce
      vitamin A deficiency in infancy. This study was conducted to determine the impact
      of maternal and infant vitamin A supplementation on antibody response to oral
      polio vaccine (OPV). DESIGN: Randomized, double blind, placebo-controlled trial.
      INTERVENTIONS: Mothers in the intervention group received 60 mg retinol
      equivalent (RE) vitamin A 3-4 weeks after delivery and their infants 7.5 mg RE
      with each OPV dose at 6, 10 and 14 weeks of age. The control group mothers and
      their infants received a placebo at each of these contacts. MAIN OUTCOMES:
      Geometric mean (GM) titer of neutralizing antibodies and proportion of children
      with protective titer to the three polioviruses at 26 weeks of age. RESULTS:
      Vitamin A supplementation increased the proportion of infants with protective
      antibody titer against poliovirus type 1 (relative risk (RR) 1.15, 95% confidence
      interval (CI) 1.03-1.28) and the GM antibody titer (ratio of GM 1.55, 95% CI 1.03
      2.31) following immunization. The proportion of infants with protective antibody
      titer against poliovirus type 2 (RR 0.99, 95% CI 0.94-1.05) or type 3 (RR 1.05,
      95% CI 0.96-1.15) was not significantly different in vitamin A and placebo
      groups. The GM antibody titer for poliovirus type 2 (ratio of GM 0.99, 95% CI
      0.64-1.54) or poliovirus type 3 (ratio of GM 1.10, 95% CI 0.69-1.75) also did not
      differ across groups. CONCLUSIONS: Vitamin A given to the mothers in the
      postpartum period and their infants with OPV did not interfere with the antibody
      response to any of the three polioviruses and enhanced the response to poliovirus
      type 1.

PMID- 11965509
TI  - Total body water measurement using bioelectrical impedance analysis, isotope
      dilution and total body potassium: a scoring system to facilitate
      intercomparison.
AB  - OBJECTIVES: (1) To develop a scale that is useful in evaluating the accuracy of
      multifrequency bioelectrical impedance analysis (MF-BIA) in the assessment of
      body water volumes against the accepted gold standard measurements based on
      isotope-dilution and total body potassium (TBK). (2) To perform a pilot test of
      the scale. DESIGN: A scale was developed to evaluate the accuracy of MF-BIA in
      the assessment of body water volumes. Questions were obtained from reading the
      scientific literature and discussions involving the four authors. Three of these
      and two additional independent readers pre-tested the scale. A weighting was
      identified for each question and a pilot test with a sample of 10 articles
      (different to those used for the questionnaire performance) was conducted. A
      further validation was carried out with a second set of 20 articles and two
      additional independent readers. RESULTS: The kappa statistic expressing the level
      of agreement between pairs of the first three authors using this scale with 10
      articles, was 0.3, 0.4 and 0.6 after the first attempt. A second evaluation after
      specific changes improved the agreement to 0.8, 0.6 and 0.8. The mean score for
      10 articles was 252+/-36 points from a total score of 400 (63+/-9%). The
      evaluation with the second set of 20 articles resulted in a kappa of 0.7 from two
      pairs of authors. The evaluation with two additional reviewers resulted in a
      kappa=0.7. CONCLUSION: A tool has been developed to assess the accuracy of the MF
      BIA technique and to identify methodological components, plan future studies and
      critically evaluate data in this area. It is likely that this tool may also be
      used to assess the accuracy of single frequency studies.

PMID- 11965510
TI  - Randomised double-blind trial of the effect of vitamin A supplementation of
      Indonesian pregnant women on morbidity and growth of their infants during the
      first year of life.
AB  - OBJECTIVE: To investigate whether supplementation with vitamin A together with
      iron of Indonesian pregnant women decreases morbidity and improves growth of
      their infants during the first year of life. DESIGN: Women from a rural area in
      West Java, Indonesia, were randomly assigned on an individual basis to double
      blind supplementation once weekly from approximately 18 weeks of pregnancy until
      delivery. Supplementation comprised 120 mg iron and 500 microg folic acid with or
      without 4800 RE vitamin A. Their newborn infants were followed up during the
      first year of life: weight, length, morbidity and food intake were assessed
      monthly. RESULTS: Infants whose mothers had taken vitamin A supplements during
      pregnancy had similar weight, length, weight gain and growth as their
      counterparts during the follow-up period. The proportions of infants with
      reported symptoms of morbidity were similar in the vitamin A plus iron group and
      the iron group. In addition immunisation coverage and feeding mode did not differ
      between the groups. All infants were breast-fed, but exclusive breast-feeding
      rapidly declined at 4 months of age. Infants with serum retinol concentrations
      >0.70 micromol/l increased their weight and length more during the first 6 months
      of life and had higher weight-for-age Z-scores during the first year of life than
      infants with serum retinol concentrations <or=0.70 micromol/l. Serum retinol
      concentrations were not associated with morbidity. CONCLUSION: In this study,
      vitamin A supplementation in conjunction with iron supplementation of pregnant
      women did not improve growth or reduce morbidity of their infants during the
      first year of life.

PMID- 11965511
TI  - Effect of obesity and insulin on immunity in non-insulin-dependent diabetes
      mellitus.
AB  - OBJECTIVE: To understand the effect of obesity and insulin on immune functions in
      non-insulin-dependent diabetes mellitus (NIDDM). SUBJECT: Fourteen obese NIDDM
      (body mass index (BMI)=30.6+/-1.1), seven non-obese NIDDM (BMI=24.2+/-0.5) and
      five obese non-NIDDM (BMI=28.3+/-0.67). INTERVENTIONS: We first examined the
      influence of insulin on the proliferation of several human cell lines. Second, we
      compared several immune functions between obese and non-obese NIDDM, and obese
      non-NIDDM patients using peripheral blood mononuclear cells. RESULT: Insulin
      decreased proliferation of T-cell lines but not that of other types of cell
      lines. Furthermore, obesity augmented the production of IL-1beta which could have
      cytotoxity against islet beta cells in NIDDM. CONCLUSION: Our data suggested that
      the pathophysiology of NIDDM could be affected by the change of immunity due to
      obesity, and the treatment of obesity in NIDDM may be important from an
      immunological aspect.

PMID- 11965512
TI  - Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To study whether Abacor, a product based on isolated soy protein with
      high and standardised levels of isoflavones and cotyledon soy fibres, was more
      effective in lowering total and LDL cholesterol than placebo. DESIGN: Randomised,
      placebo-controlled, double-blind, parallel group, single centre study. SETTING:
      Primary care in Joensuu, North Karelia, Finland. SUBJECTS: Subjects were screened
      from the patient database of the health centre; 30 were randomised to the Abacor
      group and 30 subjects to placebo. Eight subjects were withdrawn, six from the
      active group, two from the placebo group. INTERVENTION: The preparations were
      given as two daily liquid supplements in addition to the subjects' regular diets
      for 6 weeks. RESULTS: Abacor showed a statistically significant lipid-lowering
      effect as compared to placebo, although an unexpected reduction was seen in the
      placebo group. The estimated difference between active treatment and placebo was
      0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to
      reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL
      cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a
      reduction of 13.2% in the active treatment group, and 8.0% in the placebo group.
      Abacor showed a rapid onset of effect, as compared with placebo. During a wash
      out period of 4 weeks after treatment, the subjects returned to pre-treatment
      cholesterol levels. CONCLUSION: Added to a regular diet, Abacor significantly
      reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred
      within 6 weeks of treatment.

PMID- 11965513
TI  - Relationship of high energy expenditure and variation in dietary intake with
      reporting accuracy on 7 day food records and diet histories in a group of healthy
      adult volunteers.
AB  - OBJECTIVES: To assess the accuracy of reporting from both a diet history and food
      record and identify some of the characteristics of more accurate reporters in a
      group of healthy adult volunteers for an energy balance study. DESIGN:
      Prospective measurements in free-living people. SETTING: Wollongong, Australia.
      SUBJECTS: Fifteen healthy volunteers (seven male, eight female; aged 22-59 y;
      body mass index (BMI) 19-33 kg/m(2)) from the local community in the city of
      Wollongong, Australia. INTERVENTIONS: Measurement of energy intake via diet
      history interview and 7 day food records, total energy expenditure by the doubly
      labelled water technique over 14 days, physical activity by questionnaire, and
      body fat by dual-energy X-ray absorptiometry. RESULTS: Increased misreporting of
      energy intake was associated with increased energy expenditure (r=0.90, P<0.0001,
      diet history; r(S)=0.79, P=0.0005, food records) but was not associated with age,
      sex, BMI or body fat. Range in number of recorded dinner foods correlated
      positively with energy expenditure (r(S)=0.63, P=0.01) and degree of misreporting
      (r(S)=0.71, P=0.003, diet history; r(S)=0.63, P=0.01, food records). Variation in
      energy intake at dinner and over the whole day identified by the food records
      correlated positively with energy expenditure (r=0.58, P=0.02) and misreporting
      on the diet history (r=0.62, P=0.01). CONCLUSIONS: Subjects who are highly active
      or who have variable dietary and exercise behaviour may be less accurate in
      reporting dietary intake. Our findings indicate that it may be necessary to
      screen for these characteristics in studies where accuracy of reporting at an
      individual level is critical.

PMID- 11965514
TI  - Dose-response effects of a novel fat emulsion (Olibra) on energy and
      macronutrient intakes up to 36 h post-consumption.
AB  - OBJECTIVE: To investigate the dose-response effects of a novel fat emulsion
      (Olibra) on energy and macronutrient intakes up to 36 h post-consumption in non
      overweight subjects. DESIGN: A single-blind, placebo-controlled, within-subject
      cross-over design was used. SETTING: Metabolic suite of the University of Ulster,
      Coleraine. SUBJECTS: Fifty subjects (30 female, 20 male) from the student and
      staff population of the University of Ulster, Coleraine. INTERVENTIONS: Subjects
      were given in random order, 7 days apart, a 200 g portion of yoghurt containing a
      total of 15 g of fat, which varied in quantity of Olibra fat (0, 2, 4, 6 g) at
      09:00 h. At 13:00 h subjects were given ad libitum access to a range of foods.
      Amounts of food consumed were measured by covert pre- and post-consumption
      weighing of individual serving dishes. For the remainder of the day and the
      following 24 h, subjects weighed and recorded all food intakes. RESULTS: Relative
      to the control yoghurt, mean energy (7.42 vs 5.83, 5.60, 5.24 MJ), fat (97.4 vs
      74.4, 74.2, 67.5 g; 48.8 vs 46.8, 48.9, 47.6% energy), protein (59.1 vs 50.0,
      44.0, 40.8 g; 13.2 vs 13.9, 12.9, 12.8% energy), and carbohydrate (171.5 vs
      140.9, 130.2, 126.0 g; 38.0 vs 39.3, 38.2, 39.6% energy), intakes were
      progressively reduced with increasing doses of Olibra fat in the total group
      (P<0.001). A similar response was observed in the female group up to 4 g
      (P<0.001) and in the male group after 2 and 6 g (P<0.05). Energy and
      macronutrient intakes for the remainder of each study day and over the following
      24 h were significantly lower after all dose levels compared to the control
      (P<0.001). CONCLUSION: The results suggest that Olibra fat reduced the effect of
      overeating during an ad libitum lunch meal and subsequent food intake up to 36 h
      post-consumption.

PMID- 11965516
TI  - Meat and cancer: meat as a component of a healthy diet.
AB  - Based on epidemiological studies it is assumed that meat, especially red meat,
      enhances risk for cancer, particularly of the colon, breast and prostate. Meat
      and meat products are important sources of protein, some micronutrients and fat.
      High fat intake has been blamed for correlation with different diseases,
      including cancer. Meat protein is reported to contribute to cancer formation.
      However, meat, including liver, is not only composed of fat and protein, it
      contains essential nutrients which appear exclusively in meat (vitamin A, vitamin
      B12) and micronutrients for which meat is the major source because of either high
      concentrations or better bioavailability (folate, selenium, zinc). In particular,
      vitamin A, folate and selenium are reported to be cancer-preventive, with respect
      to colon, breast and prostate cancer. Taken together, meat consists of a few, not
      clearly defined cancer-promoting and a lot of cancer-protecting factors. The
      latter can be optimized by a diet containing fruit and vegetables, which contain
      hundreds of more or less proven bioactive constituents, many of them showing
      antioxidative and anticarcinogenic effects in vitro.

PMID- 11965517
TI  - Advantages and disadvantages of an iron-rich diet.
AB  - BACKGROUND AND OBJECTIVE: A review by invitation about advantages and
      disadvantages of an iron-rich diet by analyzing physiological iron requirements,
      dietary factors influencing iron absorption and the regulatory systems available
      to control iron absorption according to needs. RESULTS: The control to prevent
      iron deficiency is good but not perfect, as observed in previously described
      studies on relationships between individual iron requirements and the probability
      of iron deficiency developing in relation to diet. The control to prevent iron
      overload seems to be perfect except in the few subjects being homozygotes for
      hereditary hemochromatosis. CONCLUSIONS: A diet rich in easily available iron is
      important for covering basal iron losses, menstrual iron losses and the high iron
      requirements for growth from infancy to adolescence and for pregnancy.

PMID- 11965518
TI  - Meat consumption and cancer of the large bowel.
AB  - Since the major reviews on diet and cancer by the World Cancer Research Fund
      (WCRF) and by the British Department of Health's Committee on Medical Aspects of
      Food Policy (COMA) in 1997 and 1998, additional epidemiological studies relating
      (red) meat consumption and colorectal cancer have been published or found by
      search. These are collected here. Thirty adequate case-control studies have been
      published up to 1999 (from 16 different countries). Twenty of them found no
      significant association of (red) meat with colorectal cancer. Of the remaining 10
      studies reporting an association, some obtained statistical significance only in
      rectal or colon cancers, another only in men, not women, or found a stronger
      association with pasta and rice, or used an inadequate food list in the food
      frequency questionnaire. Fifteen cohort studies have now been published. Only in
      three were significant associations of (red) meat found with colorectal cancer.
      Two of these positive studies were from the same group in the USA (relative risk
      1.7). The results of the third positive study appear to conflict with data from
      part of the vegetarians follow up mortality study. Here, five groups of
      vegetarians (in three different countries) with socially matched controls were
      followed up (total 76 000 people). Mortality from colorectal cancer was not
      distinguishable between vegetarians and controls. While it is still possible that
      certain processed meats or sausages (with a variety of added ingredients) or
      meats cooked at very high temperature carry some risk, the relationship between
      meats in general and colorectal cancer now looks weaker than the 'probable'
      status it was judged to have by the WCRF in 1997.

PMID- 11965519
TI  - Insulin resistance and the metabolic syndrome-a challenge of the new millennium.
AB  - The term metabolic syndrome is used for describing a cluster of cardiovascular
      risk factors comprising abdominal obesity, glucose intolerance/type 2 diabetes
      mellitus, dyslipidaemia and hypertension. A concomitant presentation of all
      components of the syndrome is rare, therefore, in the view of most experts three
      out of the four main components are sufficient for defining the syndrome. Another
      recently identified component of high clinical significance is the impairment of
      the fibrinolytic system which is now frequently mentioned in extended
      definitions. This clustering of metabolic risk factors has been described in
      various combinations and given different names including insulin resistance
      syndrome or syndrome X. Unfortunately, there is no generally accepted definition
      so far. The original mentioning of the syndrome goes back to the late sixties,
      when the metabolic syndrome was described as a 'disorder of genetic adaptation
      becoming manifest following unrestricted food intake and/or muscular inacitvity'.
      In its modern meaning this term was propagated by Hanefeld and Leonhardt and by
      Kaplan, who also called the syndrome the 'deadly quartet' to emphasize its high
      atherogenic potential.

PMID- 11965520
TI  - The 'carnivore connection'--evolutionary aspects of insulin resistance.
AB  - Insulin resistance is common and is determined by physiological (aging, physical
      fitness), pathological (obesity) and genetic factors. The metabolic compensatory
      response to insulin resistance is hyperinsulinaemia, the primary purpose of which
      is to maintain normal glucose tolerance. The 'carnivore connection' postulates a
      critical role for the quantity of dietary protein and carbohydrate and the change
      in the glycaemic index of dietary carbohydrate in the evolution of insulin
      resistance and hyperinsulinaemia. Insulin resistance offered survival and
      reproductive advantages during the Ice Ages which dominated human evolution,
      during which a high-protein low-carbohydrate diet was consumed. Following the end
      of the last Ice Age and the advent of agriculture, dietary carbohydrate
      increased. Although this resulted in a sharp increase in the quantity of
      carbohydrate consumed, these traditional carbohydrate foods had a low glycaemic
      index and produced only modest increases in plasma insulin. The industrial
      revolution changed the quality of dietary carbohydrate. The milling of cereals
      made starch more digestible and postprandial glycaemic and insulin responses
      increased 2-3 fold compared with coarsely ground flour or whole grains. This
      combination of insulin resistance and hyperinsulinaemia is a common feature of
      many modern day diseases. Over the last 50 y the explosion of convenience and
      takeaway 'fast foods' has exposed most populations to caloric intakes far in
      excess of daily energy requirements and the resulting obesity has been a major
      factor in increasing the prevalence of insulin resistance.

PMID- 11965521
TI  - Meat, cancer and dietary advice to the public.
AB  - BACKGROUND: It has been claimed for many decades that meat is a risk factor for
      colorectal cancer, and that it has no compensating benefits in terms of cancer
      risk. The evidence for this has been critically reassessed. METHODS: The
      epidemiological evidence, particularly that produced in recent years, has been re
      examined to determine whether it is sufficiently consistent to warrant giving
      firm advice to the general public. RESULTS: Far from being supportive, the
      epidemiological data does not justify this claim. A large mass of evidence is
      presented from case-control studies and prospective studies, in which the data
      from Europe are not consistent with those from the United States. This is because
      of the different contexts (in terms of meal composition) within which meat is
      consumed in different countries. In fact the epidemiological data are much more
      consistent with there being a protective role for fruit, vegetables and whole
      grain cereals and no role for meat in colorectal cancer, and a protective role in
      gastric cancer. CONCLUSIONS: Meat is a good source of protein, readily available
      iron, calcium, magnesium, selenium, zinc and a range of B vitamins. Since the
      evidence for any role in colon carcinogenesis is so weak, and since such a high
      proportion of women of child-bearing age are iron deficient, the consumption of
      meat, as part of a balanced and varied diet, should be actively encouraged.

PMID- 11965522
TI  - The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic.
AB  - OBJECTIVE: Field studies of twentieth century hunter-gathers (HG) showed them to
      be generally free of the signs and symptoms of cardiovascular disease (CVD).
      Consequently, the characterization of HG diets may have important implications in
      designing therapeutic diets that reduce the risk for CVD in Westernized
      societies. Based upon limited ethnographic data (n=58 HG societies) and a single
      quantitative dietary study, it has been commonly inferred that gathered plant
      foods provided the dominant energy source in HG diets. METHOD AND RESULTS: In
      this review we have analyzed the 13 known quantitative dietary studies of HG and
      demonstrate that animal food actually provided the dominant (65%) energy source,
      while gathered plant foods comprised the remainder (35%). This data is consistent
      with a more recent, comprehensive review of the entire ethnographic data (n=229
      HG societies) that showed the mean subsistence dependence upon gathered plant
      foods was 32%, whereas it was 68% for animal foods. Other evidence, including
      isotopic analyses of Paleolithic hominid collagen tissue, reductions in hominid
      gut size, low activity levels of certain enzymes, and optimal foraging data all
      point toward a long history of meat-based diets in our species. Because
      increasing meat consumption in Western diets is frequently associated with
      increased risk for CVD mortality, it is seemingly paradoxical that HG societies,
      who consume the majority of their energy from animal food, have been shown to be
      relatively free of the signs and symptoms of CVD. CONCLUSION: The high reliance
      upon animal-based foods would not have necessarily elicited unfavorable blood
      lipid profiles because of the hypolipidemic effects of high dietary protein (19
      35% energy) and the relatively low level of dietary carbohydrate (22-40% energy).
      Although fat intake (28-58% energy) would have been similar to or higher than
      that found in Western diets, it is likely that important qualitative differences
      in fat intake, including relatively high levels of MUFA and PUFA and a lower
      omega-6/omega-3 fatty acid ratio, would have served to inhibit the development of
      CVD. Other dietary characteristics including high intakes of antioxidants, fiber,
      vitamins and phytochemicals along with a low salt intake may have operated
      synergistically with lifestyle characteristics (more exercise, less stress and no
      smoking) to further deter the development of CVD.

PMID- 11965525
TI  - A particle is not a particle is not a PARTICLE.

PMID- 11965526
TI  - Exposure assessment at a crossroads: the risk of success.

PMID- 11965527
TI  - Particulate matter and polycyclic aromatic hydrocarbon concentrations in indoor
      and outdoor microenvironments in Boston, Massachusetts.
AB  - Estimating personal exposures to air pollution is a crucial component in
      identifying high-risk populations and determining efficient control strategies.
      Because of the difficulty of comprehensively measuring personal exposure, data on
      air pollution patterns in homogenous microenvironments linked with activity data
      are often used as surrogates. In this study, we focus on strengthening the
      available information about nonresidential microenvironmental exposures to
      particulate matter and other combustion pollutants. During the summer of 2000, we
      measured ultrafine particles, fine particulate matter (PM2.5), and particle-bound
      polycyclic aromatic hydrocarbons (PAHs) outdoors and in indoor microenvironments
      in Boston, Massachusetts. In indoor microenvironments averaged across sample
      days, mean ultrafine particle concentrations ranged from 3800 to 140,000
      particles/cm(3), with 7-200 microg/m(3) of PM2.5 and 5-12 ng/m(3) of particle
      bound PAH. PM2.5 indoor-outdoor ratios generally exceeded 1 in settings with high
      levels of human activity, with lower ratios for ultrafine particles. Cooking
      activities contributed significantly to elevated levels of all three pollutants.
      Using Linear Mixed Effects models with AR-1 autoregressive correlation
      structures, 10-min average outdoor concentrations were generally weak predictors
      of indoor levels, with stronger relationships in an apartment without mechanical
      ventilation than in air-conditioned nonresidential settings. Although further
      study would be needed to determine whether these patterns could be generalized
      beyond the monitored sites, these data support previous findings and enhance our
      knowledge about nonresidential exposure patterns.

PMID- 11965528
TI  - Evaluation of ambient air concentrations of polycyclic aromatic hydrocarbons in
      Germany from 1990 to 1998.
AB  - All available polycyclic aromatic hydrocarbon (PAH) concentration data in ambient
      air obtained over the past 10 years in Germany were evaluated to clarify whether
      it is justified to use benzo(a)pyrene (BaP) as a marker compound for the total
      PAH exposure. The data basis comprises annual mean concentrations from 1990 to
      1998 supplied by the emission protection authorities of the federal states with
      additional information on the region, year and site of measurement. The data are
      very heterogeneous with respect to sample size, the number of individual PAHs
      analyzed, place of origin and year. Nine of 25 individual compounds with
      sufficient sample size (74<N<518) were submitted to an explorative descriptive
      analysis and multiple regression analysis. Six compounds were selected for factor
      analysis to evaluate whether associations can be related to one or several
      background determinants. The concentration data of BaA, BeP, BaP, DBA, BghiP,
      COR, BbF, BkF and INP are not normally distributed and demonstrate great
      variability. Location, East-West differences persisting after the German reunion
      and time characterize the distributive patterns, e.g., from 1991 to 1997, a
      significant decrease in BaP could be determined based on the data from North
      Rhine-Westphalia (1991, N=51, median 1.6 ng/m(3); 1997, N=45, median 0.7 ng/m(3);
      P<or=0.0001). The BaP concentrations in the new federal states in the East (N=80,
      median 2.2 ng/m(3)) are about twice as high compared to the ones in the old
      federal states in the West (N=438, median 1.1 ng/m(3); P<or=0.0001). BaP
      measurements taken at sites characterized by traffic (1.8 ng/m(3)), industrial
      (1.3 ng/m(3)) or urban environment (1.3 ng/m(3)) rank significantly higher
      compared to measurements taken at rural sites (0.92 ng/m(3); P<or=0.0001). Factor
      analysis of the intercorrelation matrix of BaA, BeP, BaP, DBA, BghiP and COR
      yields one factor to explain 92% of the variability of the six individual PAHs.
      BaP shows the highest factor loading. These results confirm the common practice
      to use BaP as marker compound for the PAH exposure in ambient air.

PMID- 11965529
TI  - Community-based exposure estimate for hydrogen sulfide.
AB  - Indoor and outdoor air pollution monitoring may indicate potential human exposure
      to air contaminants. Individual and population exposures to air contaminants
      depend upon many factors including time spent outdoors and indoors, permeability
      of housing structures, and mobility within a community. In this report, we
      illustrate an approach for using long-term air monitoring to establish patterns
      or changes of environmental exposures, improve validity and representativeness of
      data, and prevent exposure misclassification. Long-term air monitoring for
      hydrogen sulfide (H2S) at 14 Dakota City, Nebraska, residences identified
      differences in area-wide concentration levels, geographic locations, and seasonal
      exposures. Air data for 1999 indicated that Dakota City residents were repeatedly
      exposed, both indoors and outdoors, to moderate levels (>or=90 parts per billion
      [ppb]) of H2S. Using GIS modeling and kriging, we produced a geographic gradient
      of exposure estimate or map for ambient H2S. These findings formed the basis for
      designing two health investigations for this community.

PMID- 11965530
TI  - Development of models to predict dose of pesticides in professional turf
      applicators.
AB  - Epidemiologic studies designed to assess the chronic effects of pesticides are
      limited by inadequate measurements of exposures. Although cohort studies have
      been initiated to evaluate the effects of 2,4-dichlorophenoxyacetic acid (2,4-D)
      and other pesticides in professional turf applicators, they may have limited
      power to detect significant health risks and may be subject to bias from exposure
      measurement error. In this study, the doses of 2,4-D, mecoprop [2-(4-chloro-2
      methylphenoxy) propionic acid, MCPP] and dicamba (3,6-dichloro-o-anisic acid)
      were evaluated in a group of 98 professional turf applicators from 20 companies
      across southwestern Ontario. During a 1-week period (Saturday to Thursday), the
      volume of pesticide (active ingredient) applied was only weakly related to the
      total dose of 2,4-D absorbed (R(2)=0.21). Two additional factors explained a
      large proportion of variation in dose: the type of spray nozzle used and the use
      of gloves while spraying. Individuals who used a fan-type nozzle had
      significantly higher doses than those who used a gun-type nozzle. Glove use was
      associated with significantly lower doses. Job satisfaction and current smoking
      influenced the dose but were not highly predictive. In the final multiple
      regression models predicting total absorbed dose of 2,4-D and mecoprop,
      approximately 63-68% of the variation was explained. The future application of
      these models for epidemiologic research will depend on the availability of
      information and records from employers, the feasibility of contacting study
      subjects and cost.

PMID- 11965531
TI  - Estimating particle exposure in the Mexico City metropolitan area.
AB  - STUDY QUESTION: We examined whether methods for measuring exposure to airborne
      particles less than 10 microm in aerodynamic diameter (PM10) in the Mexico City
      metropolitan area give different estimates of PM10 levels, and the nature of
      these differences, and developed a model for estimating missing PM10 data for one
      measurement method. METHODS: Government PM10 measurements using two different
      technologies at five sites (the Sierra-Anderson PM10 High-Volume Air Sampler
      System, Hi-Vol) (every sixth day) and the Rupprecht and Patashnik Tapered Element
      Oscillating Microbalance (TEOM) monitor (daily), as well as Harvard Impactor (HI)
      data collected for research purposes from one monitoring station were matched by
      day and monitoring site, then compared visually and with basic descriptive
      statistics. We fit linear regression models with airport visual range
      measurements, meteorological data, and information on other air pollutants to
      predict the Hi-Vol measured PM10 levels for those days when direct measurements
      were not available. RESULTS: We found relatively low correlations (r ranging from
      0.46 to 0.63) between PM10 measured with the TEOM and Hi-Vol methods, and highly
      variable differences (0-70 microg/m(3)) between the means of these measurements,
      depending on monitoring site. The HI measurements had a relatively high
      correlation with the Hi-Vol measurements (r=0.90). The models developed for the
      missing Hi-Vol measurements provided a series of estimated values similar to the
      actual Hi-Vol measurements, although the estimated series did not have high
      values in the range observed in the measured data. CONCLUSIONS: The differences
      we observed in the PM10 measurements across methods in Mexico City may be
      important when studying health effects associated with particle exposure,
      evaluating method performance under conditions and operating protocols similar to
      those in Mexico City, and determining compliance with air quality standards. The
      estimated series of PM10 measures may be a useful index of exposure for use in
      studies of the effects of air pollution on health.

PMID- 11965532
TI  - Toluene diisocyanate concentration investigation among TDI-related factories in
      Taiwan and their relations to the type of industry.
AB  - OBJECTIVES: To determine nationwide 2,4- and 2,6-toluene diisocyanates (TDI)
      concentrations among polyurethane (PU) resin, PU foam, and other TDI-related
      industries in Taiwan. The ratios of 2,4-/2,6-TDI and the noncarcinogenic risk
      among these three industries were also investigated. METHOD: Personal and fixed
      area monitoring of TDI concentrations as well as questionnaires were performed
      for 26 factories in Taiwan. The modified OHSA 42 method was applied in sampling
      and analysis. Noncarcinogenic hazard index was estimated for these three
      industries based on the average concentration measurements. RESULTS: Significant
      differences of TDI concentrations were found among the three industry categories.
      For personal monitoring, PU foam was found to have the highest TDI levels [18.6
      (+/-33.6) and 22.1 (+/-42.3) ppb for 2,4- and 2,6-TDI], Others average [8.3 (+/
      18.9) and 10.2 (+/-17.2) ppb], and PU resin lowest [2.0 (+/-3.5) and 0.7 (+/-1.2)
      ppb]. The estimated average hazard indices were found to be 310-3310. CONCLUSION:
      A substantial percentage of airborne TDI concentrations among in Taiwan
      industries exceeded current TDI occupational exposure limit, and significant
      difference of TDI levels were found among the three industry categories. The
      control remedy for the tasks of charging and foaming should be enforced with the
      highest priority. A separate 2,6-TDI exposure standard is warranted.

PMID- 11965534
TI  - Human survivin is negatively regulated by wild-type p53 and participates in p53
      dependent apoptotic pathway.
AB  - Survivin is an inhibitor of apoptosis protein, which is over-expressed in most
      tumors. Aberrant expression of survivin and loss of wild-type p53 in many tumors
      prompted us to investigate a possible link between these two events. Here we show
      that wild-type p53 represses survivin expression at both mRNA and protein levels.
      Transient transfection analyses revealed that the expression of wild-type p53,
      but not mutant p53, was associated with strong repression of the survivin
      promoter in various cell types. The over-expression of exogenous survivin protein
      rescues cells from p53-induced apoptosis in a dose-dependent manner, suggesting
      that loss of survivin mediates, at least, in part the p53-dependent apoptotic
      pathway. In spite of the presence of two putative p53-binding sites in the
      survivin promoter, deletion and mutation analyses suggested that neither site is
      required for transcriptional repression of survivin expression. This was
      confirmed by chromatin immunoprecipitation assays. Further analyses suggested
      that the modification of chromatin within the survivin promoter could be a
      molecular explanation for silencing of survivin gene transcription by p53.

PMID- 11965535
TI  - Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with
      activation of the death receptor 5 pathway.
AB  - Thapsigargin (TG), by inducing perturbations in cellular Ca(2+) homeostasis, has
      been shown to induce apoptosis. The molecular mechanisms of Ca(2+) perturbation
      induced apoptosis are not fully understood. In this study, we demonstrate for the
      first time that TG-mediated perturbations in Ca(2+) homeostasis are coupled with
      activation of the death receptor 5 (DR5)-dependent apoptotic pathway in human
      cancer cells. TG selectively upregulated DR5 but had no effect on the expression
      of the other TRAIL receptor, DR4. TG also upregulated the expression of the DR5
      ligand TRAIL (tumor necrosis factor-related apoptosis inducing ligand), albeit in
      a cell-type specific manner. TG-induced apoptosis has been shown to be associated
      with activation of the mitochondrial pathway. We found that TG upregulation of
      DR5 and TRAIL was coupled with caspase 8 activation and Bid cleavage, suggesting
      that the TG-regulated DR5 pathway could be linked to the mitochondrial pathway.
      TG enhanced not only DR5 mRNA stability but also increased induction of the DR5
      genomic promoter-reporter gene. The TG-induced increase in DR5 expression
      appeared to occur as a consequence of TG-induced endoplasmic reticulum (ER)
      Ca(2+) pool depletion. Thus, we report our novel findings that ER Ca(2+) pool
      depletion-induced apoptotic signals are mediated, at least in part, via a DR5
      dependent apoptotic pathway and there appears to be a cross-talk between the
      death receptor and mitochondrial pathways.

PMID- 11965536
TI  - Identification of genes associated with head and neck carcinogenesis by cDNA
      microarray comparison between matched primary normal epithelial and squamous
      carcinoma cells.
AB  - In order to identify genes involved in head and neck carcinogenesis, we compared
      the gene expression profile in matched primary normal epithelial cells and
      primary head and neck cancer cells from the same patients. A cDNA microarray
      analysis consisting of 12 530 human genes revealed significant changes in the
      expression of 213 genes, with 91 genes being up-regulated and 122 being down
      regulated. This comprehensive list of genes includes those associated with signal
      transduction (growth factors), cell structure, cell cycle, transcription,
      apoptosis, and cell-cell adhesion. Further analysis of nine genes involved in
      cell-cell interaction, using Western blot and/or reverse transcription (RT)-PCR
      of four paired cell lines supported the reliability of our microarray analysis.
      More specifically, our study provides the first evidence that claudin-7 and
      connexin 31.1 are down-regulated in head and neck squamous cell carcinomas
      (HNSCC) compared to normal cells. These findings provide a large body of
      information regarding gene expression profiles associated with head and neck
      carcinogenesis, and also represent a source of potential targets for HNSCC
      prevention and/or therapeutics.

PMID- 11965538
TI  - P16(INK4A) is implicated in both the immediate and adaptative response of human
      keratinocytes to UVB irradiation.
AB  - The p16(INK4A-ARF) locus plays a crucial role in the control of cellular
      proliferation via both the Rb and P53 pathways. We previously demonstrated that
      this locus is altered in human skin carcinomas. In the present study we have
      studied the expression of the p16(INK4A-ARF) locus following UVB irradiation of
      normal human keratinocytes both at the mRNA (RT-PCR) and at the protein (Western
      blotting) levels. Our data confirmed that P16(INK4A) protein is induced by UVB at
      low (30 mJ cm(2)) and high (100 mJ cm(2)) doses and is observed after a single or
      repeated exposure implying that this response is involved in both the immediate
      and adaptative response to UVB. The apparent absence of induction p16(INK4A) mRNA
      suggested that P16(INK4A) protein is upregulated at the post-transcriptional
      level. Analysis by flow cytometry and BrdU staining indicated that the highest
      protein level of P16(INK4A) in the cells was associated with a G(2) cell cycle
      arrest. Comparative analysis of P16(INK4A) and P53 showed that they were
      differentially modulated in keratinocytes according to the UVB dose and regimen.
      Low, acute or repeated UVB exposures led to accumulation of both P16(INK4A) and
      p53, whereas at high UVB doses, P53 and P53-dependent genes were not induced or
      even downregulated and only a slight but reproducible stabilization of P16(INK4A)
      protein was observed. In our conditions, P14(ARF) did not seem to participate in
      the UV response in these cells as P14(ARF) protein did not vary. These results
      infer that P16(INK4A) plays a role in cell cycle regulation of keratinocytes
      submitted to UVB irradiation. They also reinforce our previous demonstration of
      the importance of inactivation of this gene in UV-induced skin carcinogenesis.

PMID- 11965537
TI  - Rac is activated by erythropoietin or interleukin-3 and is involved in activation
      of the Erk signaling pathway.
AB  - Previous studies have shown that hematopoietic cytokines, including
      erythropoietin (Epo) and interleukin (IL)-3, activate the Ras GTPase and the
      downstream Raf/Erk/Elk-1 signaling pathway. Here we report that Epo or IL-3
      rapidly and transiently activates Rac, a Rho family GTPase, in hematopoietic cell
      lines, 32D/EpoR-Wt and UT-7. The cytokine-induced activation of Rac was augmented
      in a 32D/EpoR-Wt clone that inducibly overexpresses the adaptor protein CrkL or
      the Ras guanine nucleotide exchange factor C3G, which forms a complex with CrkL.
      Furthermore, the Rac activation was enhanced or inhibited in cells inducibly
      expressing an activated Ras mutant, H-Ras61L, or a dominant negative Ras mutant,
      H-Ras17N, respectively. In addition, the cytokine-induced Rac activation was
      inhibited by a phosphatidyl-inositol 3'-kinase (PI3K) inhibitor, LY294002, which
      also inhibited the Erk activation. A dominant negative Rac mutant, Rac17N, also
      inhibited the cytokine-induced activation of Erk as well as Elk-1. On the other
      hand, activation of Akt downstream of PI3K was found to play an inhibitory role
      in cytokine activation of Erk/Elk-1. Together, these results indicate that Rac is
      activated by Epo or IL-3 at downstream of the Ras/PI3K pathway in parallel with
      Akt and plays a role in activation of the Erk/Elk-1 signaling pathway in
      hematopoietic cells.

PMID- 11965539
TI  - Anti-neovascular therapy using novel peptides homing to angiogenic vessels.
AB  - Cancer chemotherapy targeted to angiogenic vessels is expected to cause indirect
      tumor regression through the damage of the neovasculature without the induction
      of drug resistance. To develop a tool for neovasculature-specific drug delivery,
      we isolated novel peptides homing to angiogenic vessels formed by a dorsal air
      sac method from a phage-displayed peptide library. Three distinct phage clones
      that markedly accumulated in murine tumor xenografts presented PRPGAPLAGSWPGTS-,
      DRWRPALPVVLFPLH- or ASSSYPLIHWRPWAR-peptide respectively. After the determination
      of the epitope sequences of these peptides, we modified liposomes with epitope
      penta-peptides. Liposome modified with APRPG-peptide showed high accumulation in
      murine tumor xenografts, and APRPG-modified liposome encapsulating adriamycin
      effectively suppressed experimental tumor growth. Finally, specific binding of
      APRPG-modified liposome to human umbilical endothelial cells, and that of PRP
      containing peptide to angiogenic vessels in human tumors, i.e., islet cell tumor
      and glioblastoma, were demonstrated. The present study indicates the usefulness
      of APRPG-peptide as a tool for anti-neovascular therapy, a novel modality of
      cancer treatment.

PMID- 11965540
TI  - Introduction of wild-type patched gene suppresses the oncogenic potential of
      human squamous cell carcinoma cell lines including A431.
AB  - Defects in a developmental signaling pathway involving the mammalian homologue of
      the Drosophila segment polarity gene, patched are associated with human tumors
      such as basal cell carcinoma, medulloblastoma and squamous cell carcinoma. Loss
      of heterozygosity (LOH) in some of these tumor cells suggests that patched
      functions as a tumor suppressor gene. To evaluate the biological significance of
      patched mutations in human sporadic tumor cells, we constructed a VSV-G
      pseudotyped retrovirus vector carrying the wild-type patched gene and transduced
      it into two human squamous cell carcinoma (SCC) cell lines, A431 and KA, that
      express only mutant patched mRNA. When SSC cells were transduced with Ptc virus,
      colony forming activity in soft agar was drastically reduced and these cells
      recovered anchorage independent growth when Sonic hedgehog (Shh), the ligand of
      Patched (Ptc), was added into the soft agar culture. Expression of exogenous
      patched, however, had no effect on anchorage independent growth of Ras
      transformed NIH3T3 cells or SCC cell line, NA, which expresses wild-type patched
      mRNA. Cyclopamine, a specific inhibitor of the Shh/Ptc/Smo signaling pathway,
      efficiently suppressed anchorage independent growth of A431 and KA cells. These
      results indicate that loss of patched function plays a major role in the
      acquisition of oncogenic potential in these SCCs and further that Ptc virus would
      be an effective reagent for suppressing tumorigenicity of such SCCs.

PMID- 11965541
TI  - In vitro evidence for complex modes of nuclear beta-catenin signaling during
      prostate growth and tumorigenesis.
AB  - Understanding the molecular etiology of prostate cancer (CaP) progression is
      paramount for broadening current diagnostic and therapeutic modalities. Current
      interest in the role of wnt pathway signaling in prostate tumorigenesis was
      generated with the finding of beta-catenin mutation and corresponding nuclear
      localization in primary lesions. The recent finding of beta-catenin-induced
      enhancement of androgen receptor (AR) function potentially ties beta-catenin to
      key regulatory steps of prostate cell growth, differentiation, and
      transformation. By immunohistological analysis of metastatic tumors, we detected
      nuclear beta-catenin in 20% of lethal CaP cases, suggesting a more common role
      for beta-catenin in advanced disease than would be predicted by its mutation
      rate. Interestingly, beta-catenin nuclear localization was found to occur
      concomitantly with androgen-induced regrowth of normal rat prostate. These in
      vivo observations likely implicate beta-catenin involvement in both normal and
      neoplastic prostate physiology, thus prompting our interest in further
      characterizing modes of beta-catenin signaling in prostate cells. Extending our
      previous findings, we demonstrate that transient beta-catenin over-expression
      stimulates T cell factor (TCF) signaling in most CaP cell lines. Further, this
      activity is not subject to cross-regulation by phosphoinositide-3-kinase (PI3
      K)/Akt signaling, a stimulatory pathway often upregulated in CaP upon PTEN
      inactivation. Consistent with a previous report, we observed that transient beta
      catenin over-expression enhances AR-mediated transcription off two natural target
      gene promoters. However, we were unable to recapitulate beta-catenin-induced
      stimulation of ectopically expressed AR in AR-negative cells, suggesting that
      other AR-associated factors are required for this activity. Although LNCaP cells
      are capable of this mode of AR co-stimulation, stable expression of mutant beta
      catenin did not alter their proliferative response to androgen. In total, our
      characterization of beta-catenin signaling in CaP reveals the complex nature of
      its activity in prostate tissue, indicating that beta-catenin potentially
      contributes to multiple stimulatory inputs required for disease progression.

PMID- 11965542
TI  - The t(3;21) fusion product, AML1/Evi-1 blocks AML1-induced transactivation by
      recruiting CtBP.
AB  - AML1/Evi-1 is a chimeric protein that is derived from t(3;21), found in blastic
      transformation of chronic myelogenous leukemia. It is composed of the N-terminal
      AML1 portion with the DNA-binding Runt domain and the C-terminal Evi-1 portion.
      It has been shown to dominantly repress AML1-induced transactivation. The
      mechanism for it has been mainly attributed to competition with AML1 for the DNA
      binding and for the interaction with PEBP2beta (CBFbeta), a partner protein which
      heterodimerizes with AML1. It was recently found that Evi-1 interacts with C
      terminal binding protein (CtBP) to repress TGFbeta-induced transactivation. Here,
      we demonstrate that AML1/Evi-1 interacts with CtBP in SKH1 cells, a leukemic cell
      line which endogenously overexpresses AML1/Evi-1 and that AML1/Evi-1 requires the
      interaction with CtBP to repress AML1-induced transactivation. The association
      with CtBP is also required when AML1/Evi-1 blocks myeloid differentiation of
      32Dcl3 cells induced by granulocyte colony-stimulating factor. Taken together, it
      is suggested that one of the mechanisms for AML1/Evi-1-associated leukemogenesis
      should be an aberrant recruitment of a corepressor complex by the chimeric
      protein.

PMID- 11965543
TI  - MeCP2 and MBD2 expression during normal and pathological growth of the human
      mammary gland.
AB  - During the last years, a direct link between DNA methylation and repressive
      chromatin structure has been established. This structural modification is
      mediated by histone deacetylases targeted to the methylated sequences by Methyl
      Binding Proteins (MBD). Human cancer cells exhibit both a global hypomethylation
      and some localized hypermethylations suggesting that the deregulation of the
      methylation machinery is a central event in tumorigenesis. Therefore, we have
      investigated in human tissues the expression of two major MBDs, MeCP2 and MBD2,
      during the proliferation of normal breast and in benign and neoplasic breast
      tumors. Quantitation of the transcripts indicates that MBD2 mRNAs are 20-30-fold
      more abundant than MeCP2 transcripts in the adult and fetal human mammary gland.
      In pathological tissues samples MBD2 mRNA levels are significantly higher
      (P=0.001) in benign tumors compared with normal breast tissues, whereas MeCP2
      expression is not modified in these specimens. In neoplasic samples a
      deregulation of the expression of both genes was found. The amounts of MBD2 and
      MeCP2 transcripts vary greatly between samples in cancer cells compared to normal
      breast tissues or benign tumors, and in invasive ductal carcinomas the amount of
      MBD2 mRNA is significantly (P=0.03) associated with the tumor size. Taken
      together these data suggest that upregulation of MBD2 might be associated with
      breast cell proliferation. In line with this hypothesis MBD2 is also upregulated
      during the prenatal development of the human mammary gland, but in contrast to
      that observed in tumor cells, MeCP2 is also coordinately upregulated in the fetal
      breast tissues, suggesting that deregulation of MeCP2 and MBD2 occurs in human
      breast cancers.

PMID- 11965544
TI  - RASSF3 and NORE1: identification and cloning of two human homologues of the
      putative tumor suppressor gene RASSF1.
AB  - RASSF1A, one of the two major isoforms of the putative tumor suppressor gene
      RASSF1, located at 3p21.3, is inactivated in a variety of human cancers including
      lung, breast, bladder and renal cell carcinomas. We have isolated and cloned two
      human homologues of this gene, RASSF3 and NORE1, located at 12q14.1 and 1q32.1,
      respectively. Both RASSF3 and NORE1 share almost 60% homology, at the amino acid
      level, with RASSF1. The RASSF3 gene contains five exons and encodes a 247 amino
      acid protein (MW of 28.6 kDa) with a highly conserved Ras association (RalGDS/AF
      6) (RA) domain at the C-terminus. RASSF3 is ubiquitously expressed in all normal
      tissues and cancer cell lines analysed. NORE1, which is homologous to the
      previously described mouse Nore1 gene, exists in at least two spliced isoforms, A
      and B. Transcript A encodes a protein of 418 amino acids (MW or 47 kDa) while
      transcript B contains an ORF of 265 aa (MW of 30.5 kDa). Both share a RA domain,
      encoded by exons 3 through 6. NORE1A and NORE1B are expressed in most of the
      normal tissues analysed but they appear to be down-regulated in several cancer
      cell lines. However, contrary to RASSF1A, gene silencing by methylation of the
      CpG islands at which the two NORE1 transcripts initiate is not a common event in
      human primary tumors. RASSF3 and NORE1B are very similar, at the N-terminus, to
      the splice variant C of RASSF1 (RASSF1C), which does not seem to be involved in
      tumorigenesis. NORE1A is most closely related to RASSF1A, for sequence homology
      and genomic organization. However, aberrations in tumors have so far not been
      found. The presence of a Ras association domain common to NORE1, RASSF1, and
      RASSF3 suggests their possible involvement in Ras-like signaling pathways.

PMID- 11965545
TI  - The role of PI 3-kinase in the UVB-induced expression of c-fos.
AB  - The role of the PI 3-kinase signaling pathway in UVB-induced c-fos gene
      expression was investigated in a human keratinocyte cell line, HaCaT. The
      enzymatic activity of PI 3-kinase was increased threefold by 250 J/m(2) UVB.
      Inhibition of PI 3-kinase activity, via expression of a mutant p85 subunit or
      treatment with wortmannin, resulted in decreased levels of c-fos promoter
      activity and c-fos protein. Two members of the PI 3-kinase signaling pathway, Akt
      and GSK-3beta, were also found to affect c-fos transactivation. Expression of
      dominant negative Akt or wild-type GSK-3beta significantly inhibited UVB-induced
      c-fos promoter activity. In addition, when GSK-3beta activity was inhibited by
      lithium chloride, both c-fos promoter activity and protein levels increased.
      These results demonstrate that both Akt activation and GSK-3beta inactivation are
      required in the UVB-induction of c-fos. Our results demonstrate for the first
      time that UVB induction of c-fos is in part mediated by the PI 3-kinase signaling
      pathway in the HaCaT cell line. By identifying the multiple signaling pathways
      that are induced by UVB and contribute to the induction of c-fos expression, more
      drug targets may be identified to aid attempts to prevent and treat skin cancer.

PMID- 11965546
TI  - MOZ and MORF histone acetyltransferases interact with the Runt-domain
      transcription factor Runx2.
AB  - The monocytic leukemia zinc finger protein MOZ and its homologue MORF have been
      implicated in leukemogenesis. Both MOZ and MORF are histone acetyltransferases
      with weak transcriptional repression domains and strong transcriptional
      activation domains, suggesting that they may function as transcriptional
      coregulators. Here we describe that MOZ and MORF both interact with Runx2 (or
      Cbfa1), a Runt-domain transcription factor that is known to play important roles
      in T cell lymphomagenesis and bone development. Through its C-terminal SM (serine
      and methionine-rich) domain, MORF binds to Runx2 in vitro and in vivo.
      Consistent with this, the SM domain of MORF also binds to Runx1 (or AML1), a
      Runx2 homologue that is frequently altered by leukemia-associated chromosomal
      translocations. While MORF does not acetylate Runx2, its SM domain potentiates
      Runx2-dependent transcriptional activation. Moreover, endogenous MORF is required
      for transcriptional activation by Runx2. Intriguingly, Runx2 negatively regulates
      the transcriptional activation potential of the SM domain. Like that of MORF, the
      SM domain of MOZ physically and functionally interacts with Runx2. These results
      thus identify Runx2 as an interaction partner of MOZ and MORF and suggest that
      both acetyltransferases are involved in regulating transcriptional activation
      mediated by Runx2 and its homologues.

PMID- 11965547
TI  - Inactivation of p57KIP2 by regional promoter hypermethylation and histone
      deacetylation in human tumors.
AB  - To clarify the role of DNA methylation in the silencing of the expression of
      cyclin-dependent kinase inhibitor p57KIP2 seen in certain tumors, we investigated
      the methylation status of its 5' CpG island in various tumor cell lines and
      primary cancers. Dense methylation of the region around the transcription start
      site was detected in 1 out of 10 colorectal, 2 out of 8 gastric, and 6 out of 14
      hematopoietic tumor cell lines and in 5 out of 35 (14%) gastric, 6 out of 20
      (30%) hepatocellular, and 2 out of 18 (11%) pancreatic cancers; 7 out of 25 (28%)
      acute myeloid leukemia cases also showed methylation of the p57KIP2 gene, which
      strongly correlated with the CpG island methylator phenotype (P<0.001). Detailed
      mapping revealed that dense methylation of the region around the transcription
      start site (-300 to +400), but not of the edges of the CpG island, was closely
      associated with gene silencing. 5-aza-2'-deoxycytidine, a methyltransferase
      inhibitor, restored expression of p57KIP2, and chromatin immunoprecipitation
      using anti-histone H3 and H4 antibodies showed histone to be deacetylated in cell
      lines where p57KIP2 was methylated at the transcription start site. Regional
      methylation and histone deacetylation thus appear to be crucially involved in the
      silencing of p57KIP2 expression in human tumors.

PMID- 11965548
TI  - Mdm2 overexpression and p14(ARF) inactivation are two mutually exclusive events
      in primary human lung tumors.
AB  - Pathways involving p53 and pRb tumor suppressor genes are frequently deregulated
      during lung carcinogenesis. Through its location at the interface of these
      pathways, Mdm2 can modulate the function of both p53 and pRb genes. We have
      examined here the pattern of expression of Mdm2 in a series of 192 human lung
      carcinomas of all histological types using both immunohistochemical and Western
      blot analyses and four distinct antibodies mapping different epitopes onto the
      Mdm2 protein. Using Immunohistochemistry (IHC), Mdm2 was overexpressed as
      compared to normal lung in 31% (60 out of 192) of all tumors analysed, whatever
      their histological types. Western blotting was performed on 28 out of the 192
      tumoral samples. Overexpression of p85/90, p74/76 and p57 Mdm2 isoforms was
      detected in 18% (5 out of 28), 25% (7 out of 28) and 39% (11 out of 28) of the
      cases respectively. Overall, overexpression of at least one isoform was observed
      in 14 out of 28 (50%) lung tumors and concomittant overexpression of at least two
      isoforms in 7 out of 28 (25%) cases. A good concordance (82%) was observed
      between immunohistochemical and Western blot data. Interestingly, a highly
      significant inverse relationship was detected between p14(ARF) loss and Mdm2
      overexpression either in NSCLC (P=0.0089) or in NE lung tumors (P<0.0001).
      Furthermore, a Mdm2/p14(ARF) >1 ratio was correlated with a high grade phenotype
      among NE tumors overexpressing Mdm2 (P=0.0021). Taken together, these data
      strongly suggest that p14(ARF)and Mdm2 act on common pathway(s) to regulate p53
      and/or pRb-dependent or independent functions and that the Mdm2 : p14(ARF) ratio
      might act as a rheostat in modulating the activity of both proteins.

PMID- 11965549
TI  - Bax gene expression alters Ca(2+) signal transduction without affecting apoptosis
      in an epithelial cell line.
AB  - Bax is an oncogene that has proapoptotic properties but not all cells that
      express Bax undergo apoptosis. Bax may have a function unrelated to apoptosis. To
      elucidate the role of Bax in cell signaling, an epithelial cell line called SMG
      C6 was transfected with the human bax gene. Stable transfectants were studied for
      their response to carbachol, a muscarinic receptor agonist, by measuring the
      increase in intracellular free Ca(2+) and Ca(2+) influx. Carbachol-mediated
      release of Ca(2+) from intracellular stores was significantly higher in Bax
      transfectants compared to control transfectants (empty vector). Ca(2+) influx was
      also increased in Bax transfectants. Bax had no affect on the storage operated
      channels. However, the concentration of Ca(2+) in the intracellular stores (i.e.,
      mitochondria and granules) was 40-50% lower in the Bax transfectants. There was
      no significant difference in thapsigargin-mediated apoptosis in Bax transfectants
      compared to wild-type and control transfectants. Measurement of glutathione was
      reduced in the Bax transfectant. Restoration of glutathione levels with
      glutathione monoethyl ester partially normalized Ca(2+) mobilization and storage
      capacity in the mitochondria to control levels. This study shows that sub
      apoptotic levels of Bax can reduce Ca(2+) content in intracellular stores and
      Ca(2+) homeostasis. Bax may mediate these effects by reducing the levels of
      antioxidants resulting in mild oxidative stress.

PMID- 11965550
TI  - The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal
      tissues and undergoes complex alternative splicing to yield multiple protein
      isoforms.
AB  - The whey acidic protein (WAP) domain is a conserved motif, containing eight
      cysteines found in a characteristic 4-disulphide core arrangement, that is
      present in a number of otherwise unrelated proteins. WAP motifs are present in
      SLPI and elafin, two antiproteinases located on chromosome 20q12-13, in a locus
      rich in poorly characterized WAP domain proteins. One of these proteins, which
      contains two WAP domains, is HE4 (also known as WFDC2), originally described as
      an epididymis specific protein but more recently suggested to be a putative serum
      tumour marker for ovarian cancer. We have shown that HE4 is expressed in a number
      of normal human tissues outside of the male reproductive system, including
      regions of the respiratory tract and nasopharynx, as well as in a subset of lung
      tumour cell lines. Comparison of multiple HE4 cDNAs and RT-PCR products with
      genomic sequence allowed the elucidation of the genomic organization. These
      studies revealed that HE4 can undergo a complex series of alternative splicing
      events that can potentially yield five distinct WAP domain containing protein
      isoforms. These results cast doubt on the potential role of HE4 as a serum tumour
      marker specific for ovarian cancer and open the door to understanding the
      function of multiple WAP domain containing protein isoforms arising from a single
      gene.

PMID- 11965552
TI  - Spinal hydatid disease.
AB  - STUDY DESIGN: Review article on spinal involvement of hydatid disease.
      OBJECTIVES: A better understanding of this rare but clinically challenging
      disease is intended. An overview of the epidemiology, pathogenesis, presentation
      and diagnosis of spinal hydatid disease is provided. Management problems and
      frequent pitfalls are discussed as well as current therapeutic options, results
      and outcome. METHODS: Thirty-seven reports of spinal hydatid disease published
      between 1964 and 2000 were reviewed. RESULTS: Most of the reported cases of
      spinal hydatid disease presented with spinal cord compression syndrome. Due to
      the relative rarity of the problem the diagnosis was frequently made during
      surgery. Surgical intervention by decompressive laminectomy was the most frequent
      first management. Reports of anterior procedures as well as spinal stabilization
      exist. Intraoperative prophylaxis to reduce spillage as well as pharmacotherapy
      were usually instituted. Results of surgery were generally reported to be poor.
      Progressive neurological and mechanical deterioration over the years was the most
      frequently reported disease course. Anecdotal reports of alternative management
      strategies exist. CONCLUSION: Spinal hydatid disease should be considered in the
      differential diagnosis of spinal cord compression syndrome in endemic countries
      and sought after with imaging and serology. Treatment is based on surgical
      decompression. Despite therapy the disease frequently relapses with progressive
      destruction of the vertebral column and neurological deterioration. Retention of
      spinal stability is the major long term concern. Overall outcome is poor with few
      reports of disease-free long term survival.

PMID- 11965553
TI  - Surgical treatment of painful spasticity after spinal cord injury.
AB  - STUDY DESIGN: There are several conservative methods of painful spasticity
      treatment. However, conservative methods do not always provide long-term and
      complete antispastic effects in cases of spinal cord injury with severe painful
      spasticity. OBJECTIVES: The aim of the present study was to analyse and compare
      the effectiveness of myelotomy by Bischof II and Pourpre in patients with
      paraplegia and severe painful spasticity in the late period after spinal cord
      trauma. SETTING: Spinal Care Unit, Meir General Hospital, Israel. METHODS: Twenty
      patients had longitudinal T-myelotomy by the Bischof II technique and 20
      longitudinal myelotomy en croix (Pourpre). The spasticity was determined by
      evaluated muscle tone and muscle spasm according to the Ashworth and spasm
      frequency scales. The pain was determined by McGill short questionnaire. The
      results were calculated by the Wilcoxon signed rank test, by Mann-Whitney U-test
      and Students t-test. Clinical outcomes after myelotomy in-patients with chronic
      spinal cord injury and painful spasticity were evaluated after 6 months, 5 and 10
      year follow-up period. RESULTS: Pain was relieved in all cases. The best motor
      antispastic effect was achieved after Pourpre myelotomy in 18 of the patients
      (90%) were evaluated after a follow-up of 6 months, 15 patients (75%) after 5
      years, and 11 patients (64.7%) after 10 years. Following Bischof II myelotomy
      results were classified as good: in 13 patients-(65%) at 6 months; in nine
      patients (45%) at 5 years and in six patients-(40%) at 10 years. Statistical
      analysis showed no reliable relationship between the level of Spinal cord lesion
      (T4-T10) and the type of operation. No instability occurred as a result of
      antispastic operation in any patient. CONCLUSION: A higher rate of beneficial
      outcome was achieved after Pourpre myelotomy. We recommend this operation for
      patients with paraplegia and painful spasticity, who do not have hope of
      regaining voluntary motor function. However, transections of basic pathways of
      spasticity are not always sufficient for complete antispastic effects. Good
      results after the operation may deteriorate in time. Therefore further
      investigations into the mechanism of the spasticity syndrome in the spinal cord
      injured patient are required.

PMID- 11965554
TI  - Effect of cold air therapy in relieving spasticity: applied to spinalized
      rabbits.
AB  - STUDY DESIGN: Before-After trial measured prior to cold air therapy, immediately
      following, after 30 and 60 min. OBJECTIVE: To determine the effect of cold air
      therapy in relieving spasticity, the optimal intramuscular temperature, and the
      duration of spasticity relief attained by cold air therapy. SETTING: Clinical
      research laboratory, Seoul, Korea. SUBJECT: Forty-six spastic paraplegic rabbits
      with spinal cord injury. METHODS: Spastic paraplegia was induced by transection
      of spinal cord in 46 rabbits. Cold air was applied to triceps surae muscles for
      30 min at three different intramuscular temperatures (25, 30 and 32.5 degrees C).
      Clinical parameters of spasticity (muscle tone, Babinski's sign, muscle stretch
      reflex and ankle clonus) and electrophysiologic parameters (F/M ratio and H/M
      ratio) were measured immediately following, after 30 and 60 min. RESULTS: In the
      32.5 degrees C group, relief in spasticity lasted less than 30 min. In the 30 and
      25 degrees C groups, the decrease in spasticity lasted for at least 30 min
      clinically. The spasticity relief was observed only immediately following
      treatment when measured electrophysiologically. However, six out of 16 cases
      (37.5%) in the 25 degrees C group showed complete motor conduction block.
      CONCLUSION: To relieve spasticity with cold air therapy, the intramuscular
      temperature should be maintained at 30 degrees C. The duration of spasticity
      relief lasted from between 30-60 min after cold air therapy. We certify that all
      applicable institutional and governmental regulations concerning the ethical use
      of animals were followed during the course of this research.

PMID- 11965556
TI  - The stabilizing axial spinal pillar in the lumbar spine.
AB  - STUDY DESIGN: A theoretical model of spinal stability is proposed. OBJECTIVE: To
      present a biomechanical study in vitro using flexibility and loading tests of the
      normal lumbar spine and of two lumbar models of spinal stability in order to
      determine which of the lumbar middle-column model and the personal suggested
      model of lumbar central axial pillar is more resistant and stable. SETTING:
      Hospital 'Sf.Treime', Iasi, Romania. METHODS: Twenty-three fresh human cadaveric
      lumbar spines were tested with flexibility and loading tests of the intact lumbar
      functional units and of two types of spinal model specimens: 10 lumbar middle
      column models and 13 lumbar central pillar model specimens. Parameters of
      vertebral motion and vertebral compression were compared to determine the
      differences between the types of spinal models. RESULTS: The flexibility tests
      show a significant increase in motion of the lumbar middle-column model specimens
      compared to the lumbar central pillar model specimens. The lumbar central pillar
      model specimens are three times more stable compared to the middle-column models.
      The compression tests show that the lumbar central axial pillar model specimens
      were more resistant, on average by 10% (30% maximum) compared to the other model.
      CONCLUSIONS: The lumbar model formed by the axial overlapping of the posterior
      half moon of vertebral body continued by the pedicles and the articular processes
      is more stable and more resistant compared to the middle-column model of the
      three-columns theory of Denis. In the lumbar spine this central axis spinal
      pillar is the structure of spinal stability and resistance, and I propose this
      central axial spinal pillar as the stabilizing structure for all the spine.

PMID- 11965555
TI  - Socio-economic outcome of paraplegia compared to lower limb amputation.
AB  - STUDY DESIGN: The socio-economic outcome was retrospectively compared between
      patients with traumatic lower limb amputation and those with paraplegia due to a
      spinal cord injury (SCI). OBJECTIVE: To evaluate the effect of specific
      rehabilitative procedures on the socio-economic outcome. SETTING: Paraplegic
      Centre at the University Hospital in Zurich, Switzerland. METHODS: Accidents
      occurring in a collective of 1.9 million persons in Switzerland over 3 years were
      included in the study. Fifty-six persons with unilateral amputation of lower
      limbs were compared with 54 persons with paraplegia. The follow-up was assessed
      over 5 years. RESULTS: The following data was obtained in patients with
      amputations compared to those with SCI (median values): (1) hospital stay: 150
      versus 164 days; (2) the work was taken up after 689 versus 616 days; (3) the
      global average case costs amounted to SFr. 491.000 versus SFr. 606.000 during the
      first 5 years after injury; (4) the permanent degree of disability was determined
      to 40% versus 42%. Except for the global costs, all differences were not
      significant. CONCLUSIONS: There are only a few differences between the socio
      economic outcomes between patients with lower limb amputations and those with
      paraplegia. It remains unclear if the highly specialised rehabilitation services
      provided for patients with SCI accounts for the similarity since individuals with
      SCI have additional neurogenic dysfunction of the bladder and bowel.
      Alternatively, the data may suggest a need for greater rehabilitation services
      for amputees or may reflect a threshold effect in rehabilitation outcomes.

PMID- 11965557
TI  - Trajectories of target reaching arm movements in individuals with spinal cord
      injury: effect of external trunk support.
AB  - DESIGN: Deficits in trunk control due to spinal cord injury (SCI) lead to slower
      target-reaching movements of the hand. We investigated whether the movement path
      is also affected, and whether providing external support for the trunk can
      abolish the kinematic differences. OBJECTIVE: To compare movement trajectories
      between individuals with SCI and neurologically normal individuals, with and
      without external trunk support. SETTING: Neural Control/Biomechanics Laboratory,
      University of Illinois, Chicago, USA. METHODS: Five subjects with levels of
      injury between C7 and T4 were tested 3-8 years post-injury, and compared with
      five control subjects. Two targets were employed. Trajectories were recorded by a
      motion-capture system using infrared emitting markers. Peak speed and path
      curvature were calculated for the fingertip and for the acromion. RESULTS:
      Compared with control subjects, the subjects with SCI exhibited lower peak speed
      of the fingertip but not of the acromion, and less straight paths for both. When
      the trunk was supported externally, the difference in fingertip speed persisted.
      The support abolished the difference in path curvature for the fingertip but
      accentuated that for the acromion. CONCLUSION: The slower hand movements of
      individuals with SCI are not simply time-scaled versions of those of normal
      subjects, and the provision of trunk support does not erase the kinematic
      differences between the reaching movements of the two groups.

PMID- 11965559
TI  - MRI confirmed cervical cord injury caused by spinal manipulation in a Chinese
      patient.
AB  - OBJECTIVE: To report a rare case of cervical cord injury caused by spinal
      manipulation in a Chinese patient. METHOD: A 46-year-old man suffered from acute
      tetraplegia immediately after spinal manipulation by a bonesetter. There was
      nothing abnormal in the plain X-ray but Magnetic Resonance Imaging (MRI) of his
      cervical spine demonstrated cervical cord oedema at the level of C1/2. RESULT:
      The patient was treated with high doses of methylprednisolone. Coupled with
      intensive rehabilitation, the patient made a nearly complete recovery 6 months
      after injury. Repeated MRI demonstrated syrinx formation at the previous location
      of cervical cord oedema. CONCLUSION: Spinal manipulation may cause cervical cord
      injury. MRI is useful in the documentation of this injury and exclusion of other
      pathology.

PMID- 11965558
TI  - The feasibility of urethral color ultrasound imaging in the diagnosis of female
      intrinsic sphincter deficiency: preliminary results.
AB  - STUDY DESIGN: Prospective study. OBJECTIVES: To evaluate the feasibility of color
      ultrasound imaging of the urethra in association with UPP to diagnose intrinsic
      sphincter deficiency (ISD). SETTING: Italy. METHODS: We studied a group of 13
      normal female volunteers (mean age 29 years) during the estrogenic phase and a
      group of 15 patients (mean age 63.9 years) with ISD. All patients and normal
      volunteers underwent color ultrasound imaging using a 4-7 MHz convex broad band
      transducer. Translabial sagittal scans of the urethra were obtained. The color
      ultrasound parameters were optimized for detection of parenchymal slow flows. A
      subjective score of the degree of vascularization along the entire urethra was
      established as follows: (a) minimal or absent (1), (b) poor (2), (c) moderate
      (3), (d) good (4). Statistical analysis, using the non-parametric Mann-Whitney
      rank sum test, was carried out to determine differences of ultrasound scores
      between volunteers and patients. RESULTS: The statistical evaluation showed that
      the differences between the ultrasound scores in the two groups was statistically
      significant (P<0.001). CONCLUSION: We affirm that color ultrasound imaging of the
      urethra seems to be feasible and useful in association with UPP in the diagnosis
      of ISD even if this echographic investigation needs further observations.

PMID- 11965560
TI  - Spinal epidural cavernous haemangioma: a case report and review of literature.
AB  - STUDY DESIGN: A case report of purely epidural cavernous haemangioma with MRI
      appearance and pathological features. OBJECTIVE: To present a rare case of
      extradural mass with differential diagnosis. SETTING: Delhi, India. METHOD: A 55
      year-old man presented with progressive weakness and diminished sensation in both
      lower limbs. MRI demonstrated a pure extradural mass with no bony invasion.
      Histopathology of the lesion revealed a typical cavernous haemangioma. RESULT:
      The patient showed significant improvement after surgery. CONCLUSION:
      Radiological presentation could be confusing in a purely epidural cavernous
      haemangioma. Awareness of the characteristics of the lesion will facilitate
      diagnosis and treatment of the lesion.

PMID- 11965561
TI  - Multiple plasma cell granuloma of the central nervous system: a unique case with
      brain and spinal cord involvement. Case report and review of literature.
AB  - STUDY DESIGN: Single subject (male, 34 years-of-age) case report. OBJECTIVES: To
      describe a unique case of plasma cell granuloma (PCG) with simultaneous brain and
      spinal cord involvement. SETTING: Private hospital, capital city, Turkey.
      METHODS: The patient presented with headache and paraplega. T2 weighted MR images
      showed multiple hyperintense cerebral, cerebellar, brainstem and spinal cord
      lesions that enhanced homogeneously with contrast medium. The patient was
      operated on, and the two intramedullary spinal cord lesions at T11 and T12 were
      totally excised. RESULTS: After 3 months of an intense physiotherapy programme
      the patient was able to walk with help. CONCLUSION: We report for the first time,
      the occurrence of multiple, simultaneous brain and intramedullary spinal cord
      plasma cell granulomas.

PMID- 11965564
TI  - [Health in the region].

PMID- 11965562
TI  - Spontaneous external drainage of perinephric abscess in spinal cord injury
      patients through previous nephrostomy track.

PMID- 11965566
TI  - [Social capital and health].

PMID- 11965565
TI  - [Health in the region--the example of Northrhine-Westfalia (Germany)].

PMID- 11965567
TI  - [Occasion of Awarding the Salomon Neumann Medal to Prof. Dr. phil. Johannes
      Siegrist].

PMID- 11965568
TI  - [The Network "Regions of Health" of WHO and the Regional Dimensions of European
      Health Policy].

PMID- 11965569
TI  - [Preparing for the G-DRG system: portfolio analysis of the hospitals in Saxony
      Anhalt, Germany].
AB  - Diagnosis-Related Groups are scheduled for step-by-step introduction into the
      German hospital system. Initially DRG base rates will be specific to each
      hospital (i. e. in keeping with the present budget), but eventually (by 2007) a
      common base rate will be reached in each federal state. This development may have
      grave financial consequences for some hospitals where initial base rates are
      above average and hence likely to be reduced. Therefore, we grouped the
      remunerations paid by the AOK Saxony-Anhalt (i. e. the largest statutory health
      insurance company in this federal state) for a total of 308,495 hospital cases in
      fiscal year 2000 according to hospital and diagnoses, expressed them as a
      percentage difference from the average remuneration, and analysed them jointly
      with the average length of stay (LOS). We found considerable differences between
      hospitals in terms of the payments per case and the LOS, independent of the
      stratification of the cases. For example, Magdeburg University Clinical Centre
      registered hospitalisations that were short (below average) but expensive (well
      above average), hence there is less scope for further rationalization of the LOS
      in this hospital compared to others. Considerable adjustments will become
      necessary in due course when switching over from hospital-specific base rates to
      a common regional base rate.

PMID- 11965570
TI  - [Work-satisfaction and Health of Hospital Nursing and Medical Personnel].
AB  - The implementation of new service demands and increasing rationalisation measures
      exercise stress and pressure on medical and nursing personnel in German
      hospitals. However, their satisfaction and health are important quality criteria
      in the ranking of a hospital. Basing on the introduction of a new tool, an
      inquiry was conducted among the medical and nursing personnel of two hospitals (A
      and B) in respect of the quality of their working conditions. The scope of the
      questionnaires covered the nature and kind of the work, opportunities of
      professional success, management of co-operation and conflicts, physical and
      structural obstacles to smooth working as well as the management of quality.
      Finally, a scale of complaints and a burn-out scale served to assess the
      personnel's subjective health situation. The questionnaire was submitted in
      hospital A between November 1999 and February 2000 to a total of 39 doctors (58 %
      compliance) and 84 nursing personnel (47 % compliance) of the specialist
      departments concerned with internal medicine, rheumatology, urology, general and
      accident surgery. In hospital B the questionnaire was completed between March and
      July 2001 by a total of 40 doctors (54 %) and 91 nursing personnel (68 %) of two
      departments of internal medicine, surgery, neurosurgery and gynaecology.
      Comparable to other studies, the nursing personnel in both the hospitals rated
      the working conditions more negatively than the medical personnel. The
      differences, however, are more of a quantitative (number of frequency of
      problems) than of a qualitative nature (type or kind of problems). With both
      groups, problems connected with structural difficulties in working and with
      quality management were by far most important while the nursing personnel also
      underlined physical stress. Individual health condition were also classified more
      negatively by the nursing personnel than by the doctors, and the overall physical
      complaints of the nursing personnel were generally greater than with the average
      population, whereas medical personnel registered fewer complaints. Health
      promotion measures in hospitals may help to prevent negative developments. Such
      measures are too rarely translated into reality.

PMID- 11965571
TI  - [Self-exercised health care and consultation of medical aid by single-parent
      mothers or fathers - results of a federal health survey].
AB  - PURPOSE: Single parents are at high risk of economical poverty and social
      deprivation. In this study we investigated the association of single parenthood
      with self-reported health, self-perceived mental disorders and the use of medical
      services. METHODS: The public users file of the German Health Survey 1998 were
      used for secondary analysis. Single-parent mothers aged 18 to 45 with at least
      one child under the age of 18 (n = 81) were compared with two control groups of
      the same age: mothers living in traditional nuclear families (n = 104) and women
      living in partnership status without children (n = 140). RESULTS: Single-parent
      mothers report less frequently than controls of a very good or excellent health
      status and more frequently of mental complaints (differences of single items of
      10 to 15 percent). Feelings of discouragement and sadness are more common in this
      group. Overall, single-parent mothers do not use medical services more frequently
      than the control groups, but there are differences in the use of some
      specialists, especially psychotherapists. CONSEQUENCES: In respect of health,
      psychological stress is at a high level whereas the value of subjective health
      seems lower. The emphasis on situational parameters provides an insight into
      positive coping strategies and shifts the focus on influences that support health
      in a positive manner.

PMID- 11965572
TI  - [Predictive genetic testing - change in paradigms for prevention and health
      care?].
AB  - The post-genomic era promises to offer new insights into the nature of disease,
      its prevention, and treatment. But now that there is a draft code of the human
      genome, what does this knowledge mean and how might it be applied? How to use
      genetic information to promote health and prevent disease - the fundamental
      mission of public health - will be one of the most challenging tasks in future.
      Assessing the benefits and risks of predictive genetic testing and the efficacy
      of early interventions as well as exploring complex issues that have emerged (e.
      g., rapid commercialization of genetic tests, availability of and access to
      interventions, and potencial discrimination) call for public health leadership.

PMID- 11965573
TI  - Retransplantation for hepatic allograft failure: prognostic modeling and ethical
      considerations.
AB  - Retransplantation already accounts for 10% of all liver transplants performed,
      and this percentage is likely to increase as patients live long enough to develop
      graft failure from recurrent disease. Overall, retransplantation is associated
      with significantly diminished survival and increased costs. This review
      summarizes the current causes of graft failure after primary liver transplant,
      prognostic models that can identify the subset of patients for retransplantation
      with outcomes comparable to primary transplantation, and ethical considerations
      in this setting, i.e., outcomes-based versus urgency-based approaches.

PMID- 11965575
TI  - Prioritization of patients with liver cancer within the MELD system.

PMID- 11965574
TI  - Predicting the probability of progression-free survival in patients with small
      hepatocellular carcinoma.
AB  - Allocation of cadaveric livers to patients based on such objective medical
      urgency data as the Model for End-Stage Liver Disease (MELD) score may not
      benefit patients with small hepatocellular carcinomas (HCCs). To ensure that
      these patients have a fair opportunity of receiving a cadaveric organ, the risk
      for death caused by HCC and tumor progression beyond 5 cm should be considered.
      Using a Markov model, two hypothetical cohorts of patients with small hepatomas
      were assumed to have either (1) Gompertzian tumor growth, in which initial
      exponential growth decreases as tumor size increases; or (2) rapid exponential
      growth. The model tracked the number of patients who either died or had tumor
      progression beyond 5 cm. These results were used to back-calculate an equivalent
      MELD score for patients with small HCCs. All probabilities in the model were
      varied simultaneously using a Monte Carlo simulation. The Gompertzian growth
      model predicted that patients with a 1- and 4-cm tumor have 1-year progression
      free survival rates of 70% (HCC-specific MELD score 6) and 66% (HCC-specific MELD
      score 8), respectively. When assuming rapid exponential growth, patients with a 1
      and 4-cm tumor have progression-free survival rates of 69% (HCC-specific MELD
      score 6) and 12% (HCC-specific MELD score 24), respectively. Our model predicted
      that the risk for death caused by HCC or tumor progression beyond 5 cm should
      increase with larger initial tumor size in patients with small hepatomas. To
      ensure that these patients have a fair opportunity to receive a cadaveric organ,
      HCC-specific scores predicted by our model could be added to MELD scores of
      patients with HCC.

PMID- 11965576
TI  - Liver allograft iron accumulation in patients with and without pretransplantation
      hepatic hemosiderosis.
AB  - There is a paucity of data regarding hepatic allograft iron accumulation in
      patients undergoing orthotopic liver transplantation (OLT) in whom severe iron
      overload was present in the native explanted liver. Our aim is to evaluate the
      frequency and cellular distribution of stainable iron in early and late post-OLT
      hepatic allograft biopsy specimens from patients undergoing their first OLT who
      had excess iron in their native explanted liver. We compared iron-staining
      patterns in hepatic allograft biopsy specimens at approximately 1 month (early)
      and 1 to 2 years (late) post OLT in 41 patients with hepatic iron indices greater
      than 1.9 in the explanted liver (cases) with a selected group of matched controls
      without explant hemosiderosis. Our cases included 6 patients with a pre-OLT
      diagnosis of hereditary hemochromatosis and 35 patients with cirrhosis and
      secondary iron overload. Early iron deposition was mild in most cases, commonly
      affected Kupffer's cells, and was seen with similar frequency in cases and
      controls (41% v 27%; P =.29). Stainable iron was observed in 20 donor livers (12
      cases, 8 controls), and all 20 subjects showed stainable iron in 1-month hepatic
      allograft biopsy specimens. Liver samples from 35 matched pairs were studied for
      late iron deposition. Iron deposition was observed in 43% of cases versus 17% of
      controls (P =.06). In conclusion, the frequency of stainable iron in early
      hepatic allograft biopsy specimens was not different between patients with versus
      without pre-OLT hepatic hemosiderosis. There was a suggestion that patients with
      severe pre-OLT hemosiderosis had a greater frequency of iron accumulation in late
      hepatic biopsy specimens.

PMID- 11965577
TI  - Right-liver living donor transplantation for decompensated end-stage liver
      disease.
AB  - Adult-to-adult living donor liver transplantation (LDLT) for patients with
      decompensated end-stage liver disease (DELD) is controversial. Nevertheless,
      these patients are most in need of a timely liver transplant. We present the
      results of 7 patients who underwent transplantation with this procedure and
      discuss the rationale for its possible broader application. Seven of 51 patients
      who underwent right LDLT (segments 5 to 8) between August 1998 and April 2001 had
      DELD, defined as Child-Pugh-Turcotte score greater than 13 or Model for End-Stage
      Liver Disease score greater than 30. All patients also were listed for cadaveric
      liver transplantation. Mean age of the 7 transplant recipients was 54 years
      (range, 44 to 63 years). Three patients had ethyltoxic cirrhosis; 2 patients,
      hepatitis C; 1 patient, hepatitis B; and 1 patient, autoimmune hepatitis
      cirrhosis. The average intensive care unit stay was 23 days (range, 3 to 88
      days), and average hospital stay was 77 days (range, 27 to 132 days). Three
      patients are alive 31, 21, and 17 months after LDLT. At a mean follow-up of 15.1
      +/- 10 months, patient and graft survival rates are 43%. Four transplant
      recipients died day 30, 60, 117, and 180 after transplantation. Three of the
      seven donors (43%) experienced a complication. At present, all donors are well
      and have returned to their normal activities. No donors had regrets about the
      procedure, and all donors stated that they would donate again if presented with
      the same decision. In conclusion, with the lack of other therapeutic options,
      LDLT represents a timely and effective alternative to cadaveric liver
      transplantation. Better outcome is foreseeable with a decrease in
      posttransplantation complications and more experience in predicting survival of
      these critical patients.

PMID- 11965578
TI  - Adult-adult right hepatic lobe living donor liver transplantation for status 2a
      patients: too little, too late.

PMID- 11965580
TI  - Post-liver transplantation diabetes mellitus: an association with hepatitis C.
AB  - A retrospective study was performed on all liver transplant recipients from
      British Columbia from 1989 to March 2000 to determine the prevalence and
      predictive factors of diabetes mellitus (DM) post-liver transplantation. DM was
      defined as hyperglycemia requiring treatment with insulin or oral hypoglycemic
      agents. Patient characteristics, cause of liver disease at transplantation, and
      immunosuppression regimen were considered. Both univariate and multiple logistic
      regression analyses were performed. Posttransplantation DM (PTDM) occurred in 43
      of 177 transplant recipients (24%). Of these, 13 transplant recipients had DM
      pretransplantation, whereas 30 patients developed de novo PTDM. The majority of
      patients were treated with insulin (80%). In univariate analysis, transplantation
      for hepatitis C virus (HCV) liver disease was associated with a greater incidence
      of PTDM (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.46 to 6.23) and
      de novo PTDM (OR, 5.20; 95% CI, 2.25 to 11.99). Patients administered tacrolimus
      had a greater incidence of PTDM (OR, 2.04; 95% CI, 1.01 to 4.13), and there was a
      trend toward increased PTDM in older patients (mean age, 49 years). Recipient
      sex, steroid dosage, and acute rejection were not predictive of PTDM. The
      incidence of graft loss and death rates were similar between the two groups. On
      logistic regression, HCV was the only independent predictor of PTDM (OR, 4.12;
      95% CI, 1.91 to 8.90) and de novo PTDM (OR, 6.02; 95% CI, 2.55 to 14.20). In
      conclusion, DM post-liver transplantation is a common occurrence and is
      associated with HCV.

PMID- 11965579
TI  - A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis
      C virus-infected patients awaiting liver transplantation.
AB  - Decompensated liver disease associated with chronic hepatitis C virus (HCV)
      infection is the most common indication for liver transplantation. It was shown
      previously that greater pretransplantation HCV titers are associated with
      relatively poor patient and graft survival. The tolerability and efficacy of
      antiviral therapy in patients with decompensated liver disease are not known. We
      conducted a pilot study to determine the likely tolerability and efficacy of
      pretransplantation antiviral therapy with interferon alfa-2b, with or without
      ribavirin. HCV RNA-positive patients at or near the top of their respective
      waiting lists were randomly assigned to one of three treatment regimens until the
      time of liver transplantation: (1) group A, interferon alfa-2b, 1 x 10(6) U/d;
      (2) group B, interferon alfa-2b, 3 x 10(6) U three times weekly; or (3) group C,
      interferon alfa-2b, 1 x 10(6) U/d, plus ribavirin, 400 mg twice daily. Less than
      half the patients screened met entry criteria, with thrombocytopenia and
      leukopenia the most common reasons for exclusion. Fifteen patients were
      administered antiviral therapy; three patients in group A and six patients each
      in groups B and C. Loss of detectable HCV RNA was seen in 33% of patients,
      whereas 55% had a decrease in viral titers on therapy. Twenty-three adverse
      events occurred, including 20 serious adverse events. Thrombocytopenia was the
      most common adverse event. Two infectious complications occurred; one of these
      had a fatal outcome. We conclude that although pretransplantation antiviral
      therapy may reduce HCV titers in a minority of patients who meet treatment
      initiation criteria, adverse events associated with therapy are frequent and
      often severe in patients with Child's class B and C cirrhosis.

PMID- 11965581
TI  - Impact of cytomegalovirus infection, year of transplantation, and donor age on
      outcomes after liver transplantation for hepatitis C.
AB  - Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT)
      is almost universal. However, variables that hasten the progression of allograft
      injury have not been fully defined. Cytomegalovirus (CMV) is a common infection
      post-LT, and its impact on the course of post-LT HCV infection remains unclear.
      We investigated the impact of CMV infection on patient and graft outcomes in 93
      consecutive HCV-infected liver transplant recipients. Data were collected
      prospectively, with surveillance cultures for CMV and protocol liver biopsies.
      CMV infection (defined as isolation of CMV from blood and treatment with
      ganciclovir) occurred in 25 patients (26.9%). Graft failure (defined as
      cirrhosis, relisting for LT, re-LT, or death) was significantly more common in
      CMV-positive compared with CMV-negative patients (52% v 19.1%; P =.002). Fibrosis
      stage 2 or greater on the 4-month liver biopsy specimen was more common in CMV
      infected patients (45% v 16.4%; P =.01). Patients who underwent LT in more recent
      years had an increased risk for graft failure. Donor and recipient age, CMV
      infection, and mycophenolate mofetil use were significantly associated with graft
      failure in a stepwise multivariate analysis. CMV infection occurs in
      approximately one quarter of HCV-infected liver transplant recipients and is an
      independent risk factor for graft failure in these patients. Whether CMV mediates
      this by inducing increased immunosuppression or directly enhancing HCV
      replication requires further study.

PMID- 11965583
TI  - Outcome of liver transplantation for patients with pulmonary hypertension.
AB  - It is generally believed that pulmonary hypertension (PHT) adversely affects
      outcome after liver transplantation (LT). Most transplant units consider severe
      PHT to be an absolute contraindication to LT. We examined the outcome of 145
      patients who underwent LT between 1997 and 1999. Pulmonary artery pressures
      (PAPs) had been measured before surgery. Pre-LT workup included
      electrocardiography and echocardiography for the majority of patients. Also, the
      liver unit database was screened for patients with known PHT who had undergone LT
      before 1997. Based on pulmonary flotation catheter measurements made after the
      induction of anesthesia for LT, PHT was defined as mild or moderate to severe if
      the mean PAP (MPAP) exceeded 25 and 35 mm Hg, respectively. The incidence of PHT
      was 26% (38 of 145 patients); 31 of 38 patients had mild PHT. Kaplan-Meier
      survival analysis did not show a significant survival benefit for patients with
      normal PAPs compared with patients with PHT (all, mild, moderate to severe). For
      surviving patients, the duration of ventilation and intensive care unit stay was
      unaffected by PHT. Four of 5 patients (identified from the database 1982 to 1999)
      with MPAPs greater than 40 mm Hg survived LT by more than 1 year. PHT of this
      severity was usually associated with specific and suggestive abnormality of the
      echocardiogram. Mild PHT is common and does not affect patient outcome after LT.
      Moderate and severe PHT are uncommon. Our analysis suggests that when the cardiac
      index is preserved, the majority of patients with moderate and severe PHT can
      survive LT, and they will not die of PHT during long-term follow-up.
      Echocardiography detects most severe PHT, but not mild and moderate PHT.

PMID- 11965582
TI  - Fate of hepatocyte and sinusoidal lining cell function and kinetics after
      extended cold preservation and transplantation of the rat liver.
AB  - We investigated the chronological profile of graft damage and recovery after
      liver cold ischemia-reperfusion (I/R) injury, with particular attention to the
      role of apoptosis on hepatocyte and sinusoidal endothelial cell (SEC) damage.
      Male Lewis rats underwent rearterialized orthotopic liver transplantation using
      grafts subjected to a short (University of Wisconsin [UW] solution for 1 hour
      [UW1h]) and prolonged period (UW16h) of cold preservation. Experiments were
      performed immediately after preservation and 4 hours, 24 hours, 3 days, and 7
      days after reperfusion. At each time, graft function, incidence of apoptotic
      cells, expression of the epitope recognized by a monoclonal antibody specific to
      rat SECs (SE-1), and incidence of proliferating cells were estimated. In the
      UW16h group, the proportion of apoptotic SECs was markedly elevated at 4 hours.
      The incidence of hepatocyte apoptosis was very low, although massive hepatocyte
      necrosis was evident at 24 hours. The incidence of proliferating hepatocytes and
      SECs peaked at 3 days, then returned to normal by 7 days. SE-1 expression was
      reduced immediately after preservation, followed by a marked reduction at 4 and
      24 hours after reperfusion, and expression returned to normal by 7 days. Although
      SEC apoptosis was induced in the early phase of cold I/R injury, hepatocyte
      damage developed without the occurrence of apoptosis. Regeneration of both
      hepatocytes and SECs after cold I/R injury peaked at 3 days and was complete by 7
      days, whereas functional recovery of these cell populations was complete 3 days
      after reperfusion.

PMID- 11965584
TI  - Editorial: Pulmonary hypertension, (high) risk of orthotopic liver
      transplantation, and some lessons from "primary" pulmonary hypertension.

PMID- 11965585
TI  - Utility of pulse oximetry in the detection of arterial hypoxemia in liver
      transplant candidates.
AB  - Hepatopulmonary syndrome, arterial hypoxemia caused by intrapulmonary
      vasodilatation, occurs in approximately 10% of patients with cirrhosis. The
      severity of hypoxemia affects liver transplant candidacy and is associated with
      increased morbidity and mortality posttransplantation. Screening guidelines for
      detecting the presence of arterial hypoxemia do not exist. The aim of this study
      is to investigate the accuracy and utility of pulse oximetry in the detection of
      hypoxemia (PaO(2) < 70 mm Hg) in patients with cirrhosis. Two hundred prospective
      liver transplant candidates were compared with 94 controls. Arterial
      oxyhemoglobin saturation was obtained by pulse oximetry (SpO(2)) and compared
      with simultaneous arterial blood gas (ABG) oxyhemoglobin values (SaO(2); bias =
      the difference). PaO(2), carboxyhemoglobin, methemoglobin, and routine clinical
      and biochemical parameters were investigated to account for the bias. SpO(2)
      overestimated SaO(2) in 98% of patients with cirrhosis (mean bias, 3.37%; range, 
      1% to 10%). Forty-four percent of patients with cirrhosis and controls had a bias
      of 4% or greater. No clinical or biochemical parameters of cirrhosis accounted
      for the overestimation of pulse oximetry. Twenty-five subjects with cirrhosis
      were hypoxemic, and an SpO(2) of 97% or less showed a sensitivity of 96% and a
      positive likelihood ratio of 3.9 for detecting hypoxemia. An SpO(2) of 94% or
      less detected all subjects with an arterial PaO(2) less than 60 mm Hg. Pulse
      oximetry significantly overestimates arterial oxygenation, and the inaccuracy is
      not influenced by liver disease. Nevertheless, pulse oximetry can be a useful
      screening tool to detect arterial hypoxemia in patients with cirrhosis, but a
      higher threshold for obtaining an ABG must be used.

PMID- 11965586
TI  - The potential role of bone marrow transplantation in augmenting donor-derived
      immunity to hepatitis B after rat liver transplantation.
AB  - Adoptive transfer of immunity to hepatitis B virus (HBV) is not provoked solely
      by bone marrow, but also by liver transplantation, although transiently. In the
      current study, simultaneous bone marrow transplantation, which possibly can
      increase the number of antibody-secreting cells, was performed to augment the
      efficacy of transferring HBV immunity. Stimulation of donor-derived immune cells
      by postoperative vaccination was used to investigate whether a secondary immune
      response can be induced in recipients. Orthotopic liver transplantation (n = 28),
      performed in three rat strain combinations representing different genetic
      constellations, was compared with bone marrow-augmented liver transplantation (n
      = 21). Donors had been vaccinated twice with recombinant hepatitis B surface
      antigen (HBsAg). Recipients surviving more than 10 weeks received a boost
      vaccination. All animals were monitored weekly for the presence of antibodies to
      HBsAg (anti-HBs). Effective anti-HBs titers were measured in 82% of liver
      recipients (23 of 28 recipients) and lasted from 2 to 9 weeks. Ninety percent of
      bone marrow-augmented liver recipients (19 of 21 recipients) seroconverted, with
      anti-HBs persisting from 2 to 12 weeks. A greater seroconversion rate, prolonged
      titer duration, and different pattern of titer development were observed in bone
      marrow-augmented liver recipients, although statistical significance could not be
      obtained because of the small numbers of comparable animals. Posttransplantation
      vaccination in recipients of combined grafts did not arouse a typical secondary
      antibody response, but showed a tendency toward an earlier and stronger response
      to vaccine in comparison to recipients without immune transfer. Simultaneous bone
      marrow transplantation showed an augmenting, but limited, effect on humoral
      immune transfer. Therefore, other potentially promising cellular strategies, such
      as transfer of in vivo and ex vivo stimulated antigen-specific cells should be
      pursued further. Improvement of the effect of postoperative vaccination possibly
      can be achieved by optimizing the immunization protocol.

PMID- 11965587
TI  - Effectiveness of preoperative selective portal vein embolization before extensive
      hepatic resection.

PMID- 11965588
TI  - Withdrawal of immunosuppression in liver transplant recipients: is this as good
      as it gets?

PMID- 11965589
TI  - Aberrant right hepatic artery: a mockery.

PMID- 11965590
TI  - Hepatitis C and mycophenolate mofetil--a clarification.

PMID- 11965592
TI  - p53 and matrix metalloproteinases in rheumatoid arthritis: tip of an angiogenic
      iceberg?

PMID- 11965593
TI  - Presentation and prognosis of the shrinking lung syndrome in systemic lupus
      erythematosus.
AB  - BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) may affect all the
      components of the respiratory system, including upper airways, lung parenchyma,
      pulmonary vasculature, pleura, and respiratory muscles. The shrinking lung
      syndrome (SLS) is a rare complication of SLE. This study describes the presenting
      features, investigation findings, treatment measures, and outcome of 7 patients
      with SLE and SLS. METHODS: Five patients with SLE/SLE were chosen retrospectively
      by examination of patient records, and 2 patients were chosen prospectively. All
      patients attended St. Thomas' Hospital or the Royal London Hospital between 1984
      and 2001, with a total population of 2650 patients with SLE. RESULTS: Clinical
      features included dyspnea and pleuritic chest pain. Chest x-ray films showed
      small but clear lung fields, or basal atelectasis, with diaphragmatic elevation.
      No evidence of major parenchymal lung or pleural disease was found on the
      computerized tomography scan. Lung volumes were reduced on pulmonary function
      testing (PFT) in a restrictive pattern. Treatment of SLS included theophylline,
      increase in corticosteroid dosage, and intensification of immunosuppressive
      medication to include methotrexate or cyclophosphamide. During follow-up, 5 of 7
      patients showed objective evidence on PFT of stabilization or improvement.
      CONCLUSIONS: The long-term prognosis of our SLS patients was reasonable,
      highlighting the importance of establishing a correct diagnosis and in particular
      differentiating it from fibrosing lung disease. Immunosuppressive therapy was
      helpful in stabilizing SLS and improving respiratory symptoms and PFT in some
      cases. RELEVANCE: SLS represents a rare complication of SLE, and it is important
      to be aware of its presenting features and prognosis.

PMID- 11965594
TI  - p53, proto-oncogene and rheumatoid arthritis.
AB  - OBJECTIVE: To review the literature published in the past 6 years concerning the
      role of p53 tumor-suppressor protein in rheumatoid arthritis (RA). METHODS: A
      MEDLINE search was performed to identify all publications that covered the role
      of p53 in RA. In addition, selected articles related to proto-oncogenes and
      matrix metalloproteinases were included in this review. RESULTS: p53 protein is
      expressed in RA fibroblast-like synoviocytes (FLSs), and its overexpression is a
      characteristic feature of RA. The overexpression of p53 is probably induced by
      DNA strand breaks caused by the genotoxic environment of RA joints, in some cases
      because of p53 mutations. Independent studies from 3 groups indicated that p53
      mutations can and do occur in RA synovial tissue samples derived from a subset of
      RA patients. Inactivation of p53 may contribute to the invasiveness of FLSs and
      to the high-level expression of cartilage degradation enzymes as well. Gene
      transfer or gene knockout studies using a collagen-II-induced RA animal model to
      examine the role of p53 in RA have been reported. Initial results are positive
      and indicate that gene transfer of p53 may be clinically useful for the
      management of RA. CONCLUSIONS: p53 protein is expressed in RA FLSs, and its
      overexpression is a characteristic feature of RA. p53 mutations occur in the
      synovial tissues derived from a subset of RA patients. The clinical implications
      of p53 expression and the functional importance of somatic mutations in RA,
      however, are still unclear. Further research is needed to fully understand the
      implications of these findings and develop corresponding new therapeutic
      strategies.

PMID- 11965595
TI  - Splenic rupture as the presenting manifestation of vasculitis.
AB  - BACKGROUND: Although underreported, histologic splenic involvement in Wegener's
      granulomatosis (WG) is not unusual. Splenic rupture in association with WG,
      however, is rare. Only 2 cases of nontraumatic splenic rupture have been reported
      as the initial feature of WG. Isolated cases of splenic rupture also have been
      noted in rheumatoid arthritis, systemic lupus erythematosus, and polyarteritis
      nodosa. OBJECTIVE: To report the third case of splenic rupture as the presenting
      feature of WG and review the literature concerning splenic rupture in other
      rheumatologic diseases to better delineate a mechanism for this rare occurrence.
      METHODS: Descriptive case report of 1 patient with WG with antecedent splenic
      rupture and a review of the relevant literature using a MEDLINE search from 1950
      to 2001. RESULTS: Our patient presented with symptoms and signs of WG 2 weeks
      after nontraumatic splenic rupture. Two similar cases have been reported: one
      showed splenic vasculitis histologically and the other only a neutrophilic
      infiltration at the site of the splenic tear and subcapsular zone after surgery.
      Although splenic capsular and pulp hemorrhage alone without signs of vasculitis
      were noted in our patient, no other cause (ie, hematologic, infectious,
      neoplastic, or otherwise) for splenic rupture was found. CONCLUSIONS AND
      RELEVANCE: As in the 2 reported cases, WG may have been responsible for splenic
      rupture in our patient. Regardless, early evaluation for connective tissue
      disease in a patient with spontaneous splenic rupture without apparent cause
      merits consideration, as it may affect patient follow-up and treatment.

PMID- 11965596
TI  - Renal Behcet's disease: a cumulative analysis.
AB  - OBJECTIVE: To analyze cumulated data about renal involvement in Behcet's disease
      (BD) and to report on 6 patients with BD and renal problems. METHODS: We found
      reports of 159 patients (including our patients) with BD and specific renal
      disease (amyloidosis 69, glomerulonephritis [GN] 51, renal vascular disease 35,
      and interstitial nephritis 4) in our survey. RESULTS: The frequency of renal
      problems among BD patients has been reported to vary between 0% to 55%. Male
      gender is a risk factor for all types of renal BD. Nephrotic syndrome was present
      in 83% of patients with amyloidosis, and renal failure was common at the time of
      diagnosis. The mean interval between the initial manifestation of BD and
      diagnosis of amyloidosis was shorter in men than in women (P =.02). AA-type
      amyloid fibrils were shown in all cases studied. Vascular involvement was common
      in the patients with amyloidosis (60%). The renal findings in GN show a wide
      spectrum, from asymptomatic hematuria and/or proteinuria to rapidly progressive
      GN. Several types of glomerular lesions ranging from minor glomerular changes to
      crescentic glomerulonephritis are observed in BD. The common types of glomerular
      lesions among the reported cases are crescentic GN, proliferative GN, and
      immunoglobulin A (IgA) nephritis. Aneurysms may be located throughout the renal
      artery, from the orifice of the main artery to intrarenal microaneurysms. Another
      type of renal disease (amyloidosis or GN) and other major vascular involvement
      were present in all cases with renal vein thrombosis. Hypertension is common
      among patients with renal artery aneurysm or stenosis. Microscopic vascular
      disease was described in 4 patients. CONCLUSIONS: Based on data in the
      literature, we suggest that renal involvement in BD is more frequent than has
      been recognized, although it is most often mild in nature. Amyloidosis is one of
      the prognostic factors affecting survival. Patients with vascular involvement
      carry high risk for amyloidosis, and administration of colchicine to these
      patients may be beneficial. More evidence is needed to accept interstitial
      nephritis as a manifestation of BD. In spite of some difficulties, hemodialysis
      and renal transplantation are safe treatment options in BD-related uremia.

PMID- 11965597
TI  - Agranulocytosis in Sjogren's syndrome: two case reports and analysis of 11
      additional reported cases.
AB  - OBJECTIVES: To report 2 patients who presented with agranulocytosis that was
      found to be immune-mediated and associated with occult primary Sjogren's syndrome
      (primary SS) and to identify and study similar cases reported in the literature.
      METHODS: Two patients encountered in 2 large medical centers over a period of 5
      years were studied in detail. All reported cases of agranulocytosis in primary SS
      identified through a MEDLINE search were reviewed. RESULTS: Two patients
      presented with marked systemic symptoms alone or associated with recurrent
      infections. Agranulocytosis with either a pattern of maturation arrest or a
      hypercellular reactive bone marrow was found and was associated with "acute
      phase" markers, hypergammaglobulinemia, a small paraprotein peak, and high
      rheumatoid factor titers. A diagnosis of immune-mediated agranulocytosis
      associated with an occult primary SS was established and was successfully treated
      with intravenous immunoglobulins or prednisone. Both patients subsequently
      developed skin vasculitis. This rare association of agranulocytosis and Sjogren's
      syndrome was identified in 11 other cases and was the presenting manifestation of
      primary SS in 10 of 13 (77%) patients. CONCLUSIONS: Agranulocytosis should be
      recognized as a rare but well-established association of primary SS. Bone marrow
      neutrophil production may be affected, or neutrophils may be destroyed in the
      circulation, by both humoral and cellular immune-mediated mechanisms.
      Agranulocytosis or neutropenia should be added to the varied hematologic
      manifestations of primary SS and may be its presenting feature and an important
      clue to diagnosis.

PMID- 11965598
TI  - Vertebral sarcoidosis: clinical and imaging findings.
AB  - OBJECTIVE: To report our experience with 3 cases of vertebral sarcoidosis (VS)
      and review the available literature. METHODS: We retrospectively analyzed 3
      patients with VS, with special emphasis on radiologic imaging. The literature was
      reviewed using the MEDLINE database. RESULTS: In 2 cases, VS was the first
      manifestation of sarcoidosis. Severe pain was present in all patients. Chest
      radiographs showed normal results. Therapy with corticosteroids and calcitonin
      relieved the pain. In 2 patients, the pathologic vertebral magnetic resonance
      imaging abnormalities normalized with treatment. CONCLUSIONS: Although bone
      lesions in sarcoidosis may occur throughout the entire skeleton, axial
      involvement is rare. VS may be the initial presentation of the disease, and pain
      frequently is present. This condition is usually responsive to glucocorticoids.
      Magnetic resonance imaging may be helpful in monitoring the response to
      treatment.

PMID- 11965599
TI  - Peritoneal sarcoidosis.

PMID- 11965601
TI  - Current status of radiolabeled peptides in nuclear medicine diagnosis and
      therapy.

PMID- 11965602
TI  - Radiolabeled peptides in diagnosis and tumor imaging: clinical overview.
AB  - The authors briefly review radiopeptides currently approved for use in the United
      States. They present a short review of the peptide somatostatin's actions and
      also note the five somatostatin receptors (SSTRs) to which the peptide and its
      synthetic analogs octreotide, lanreotide, and vapreotide bind. The many
      conditions besides neuroendocrine tumors having SSTRs are listed. Labeled
      octreotide and the other two analogues have a strong affinity for SSTR2 and
      SSTR5, which thereby produce positive imaging. The various neuroendocrine tumors
      best imaged by somatostatin receptor scintigraphy (SRS) are discussed, and the
      exceptions (insulinoma and medullary thyroid carcinoma) are noted to be seen
      better with labeled VIP and (99m)Tc-dimethylsuccinic acid (DMSA), respectively.
      SRS and VIP receptor scintigraphy are also noted to image many nonneuroendocrine
      tumors, which often have appropriate receptors. Several of the currently emerging
      and very effective new imaging techniques are described. These include (99m)Tc
      DMSA for medullary thyroid carcinoma, (18)F dihydroxyphenylalanine positron
      emission tomography, and C(11) 5-hydroxytryptophan positron emission tomography
      scanning for all neuroendocrine tumor, but especially carcinoid tumor,
      metastases. The special role of SRS in identifying gastric carcinoid tumors in
      hypergastrinemic patients is reviewed. Various pitfalls in interpreting SRS are
      presented and receptor-enhancing techniques described. Besides use of SRS (mainly
      Octreoscan, Mallinckrodt Medical, St. Louis, MO) only for detecting and
      localizing primary tumors and metastases for staging, there are many additional
      special uses for clinical management of SRS-positive tumors. These include the
      intraoperative use of the handheld gamma-detecting probe. A brief enumeration is
      given of the most promising of other non-SST G-protein-coupled receptors and
      ligands currently under development. Finally, we have posed a number of questions
      for which answers are needed in the immediate future to facilitate better
      imaging. Extrapolations of current knowledge and experience with radiolabeled
      peptide pharmaceutical imaging are converted to reasonable speculations of
      anticipated future developments in this field.

PMID- 11965603
TI  - Somatostatin receptor imaging.
AB  - [(111)In-DTPA(0)]octreotide is a radiopharmaceutical with a great potential for
      the visualization of somatostatin receptor-positive tumors. The overall
      sensitivity of Somatostatin Receptor Imaging (SRI) to localize neuroendocrine
      tumors is high. In a number of neuroendocrine tumor types, as well as in
      Hodgkin's disease, inclusion of SRI in the localization or staging procedure may
      be very rewarding, either in terms of cost-effectiveness, patient management, or
      quality of life. The value of SRI in patients with other tumors, like breast
      cancer, or in patients with granulomatous diseases, has to be established. The
      development of Peptide Receptor Radionuclide Therapy (PRRT) is expected to
      stimulate peptide receptor imaging.

PMID- 11965604
TI  - Somatostatin receptor imaging of non-small cell lung cancer with 99mTc
      depreotide.
AB  - Several tumors overexpress somatostatin receptors (SSTR) and can thus be imaged
      with radiolabeled analogues of somatostatin. Tc-99m depreotide is a new
      radiolabeled somatostatin analogue that shows high affinity for SSTR2, SSTR3, and
      SSTR5 subtypes. It has been recently FDA-approved for use in the evaluation of
      indeterminate solitary pulmonary nodules. SPECT with Tc-99m depreotide is highly
      accurate in this clinical setting and may be preferable to FDG-PET because of its
      lower cost and wider availability. Large studies are also underway to evaluate
      the accuracy of Tc-99m depreotide in staging of lung cancer.

PMID- 11965605
TI  - Cholecystokinin-B/Gastrin receptor-targeting peptides for staging and therapy of
      medullary thyroid cancer and other cholecystokinin-B receptor-expressing
      malignancies.
AB  - The high sensitivity of the pentagastrin stimulation test in detecting primary or
      metastatic medullary thyroid cancer (MTC) suggests a widespread expression of the
      corresponding receptor type on human MTC. Indeed, autoradiographic studies
      demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90%
      of MTCs, but also in a high percentage of small-cell lung cancers, stromal
      ovarian tumors, and potentially a variety of other tumors, including
      gastrointestinal adenocarcinomas, neuroendocrine tumors, and malignant glioma.
      The aim of our work was to develop and systematically optimize suitable
      radioligands for targeting CCK-B receptors in vivo and to investigate their role
      in the staging and therapy of MTC and other CCK-B receptor expressing
      malignancies. For this purpose, a variety of CCK/gastrin-related peptides, all
      having in common the C-terminal CCK-receptor binding tetrapeptide sequence-Trp
      Met-Asp-PheNH(2) or derivatives thereof, were investigated. They were members of
      the gastrin or cholecystokinin families or possessed characteristics of both,
      which differ by the intramolecular position of a tyrosyl moiety. Their stability
      and affinity were studied and optimized in vitro and in vivo; their
      biodistribution and therapeutic efficacy were tested in preclinical models. Best
      tumor uptake and tumor to nontumor ratios were obtained with members of the
      gastrin family, because of their superior selectivity and affinity for the CCK-B
      receptor subtype. Radiometal-labeled derivates of minigastrin showed excellent
      targeting of CCK-B receptor expressing tissues in animals and healthy human
      volunteers. Preclinical therapy experiments in MTC-bearing animals showed
      significant antitumor efficacy. In a subsequent clinical study, 45 MTC patients
      with metastatic MTC were investigated; 23 had known and 22 had occult disease.
      CCK-B receptor scintigraphy was performed with (111)In-diethylenetriamine
      pentaacetic acid-d-Glu(1)-minigastrin. The normal organ uptake was essentially
      confined to the stomach (and, to a lesser extent, to the gallbladder and, in
      premenopausal women, to normal breast tissue) as a result of CCK-B receptor
      specific binding and to the kidneys, as excretory organs. All tumor
      manifestations known from conventional imaging were visualized as early as 1 hour
      postinjection, with increasing tumor to background ratios over time; at least 1
      lesion was detected in 20 of 22 patients with occult disease (patient-based
      sensitivity, 91%). Among them were local recurrences and lymph node, pulmonary,
      hepatic, splenic, and bone (marrow) metastases. Eight patients with advanced
      metastatic disease were injected in a dose-escalation study with potentially
      therapeutic activities of a (90)Y-labeled minigastrin derivative at 4 to 6-week
      intervals (30-50 mCi/m(2) per injection for a maximum of 4 injections).
      Hematologic and renal toxicities were identified as the dose-limiting toxicities
      at the 40 and 50 mCi/m(2) levels. Two patients experienced partial remissions,
      and 4 experienced stabilization of their previously rapidly progressing disease.
      These data suggest that CCK-B receptor ligands may be a useful new class of
      receptor-binding peptides for diagnosis and therapy of a variety of (CCK-B
      receptor expressing) tumor types. They allow for sensitive and reliable staging
      of patients with metastatic MTC. Initial therapeutic results are promising, but
      nephrotoxicity is a major concern to be solved.

PMID- 11965606
TI  - Phase I study of peptide receptor radionuclide therapy with [In-DTPA]octreotide:
      the Rotterdam experience.
AB  - Fifty patients with somatostatin receptor-positive tumors were treated with
      multiple doses of [(111)In-diethylenetriamine pentaacetic acid(0)]octreotide.
      Forty patients were evaluable after cumulative doses of at least 20 GBq up to 160
      GBq. Therapeutic effects were seen in 21 patients: partial remission in 1
      patient, minor remissions in 6 patients, and stabilization of previously
      progressive tumors in 14 patients. Our results thus underscore the therapeutic
      potential of Auger-emitting radiolabelled peptides. The toxicity was generally
      mild bone marrow toxicity, but 3 of the 6 patients who received more than 100 GBq
      developed a myelodysplastic syndrome or leukemia. Therefore, we consider 100 GBq
      as the maximal tolerable dose. With a renal radiation dose of 0.45 mGy/MBq (based
      on previous studies) a cumulative dose of 100 GBq [(111)In-DTPA(0)]octreotide
      will lead to 45Gy on the kidneys, twice the accepted limit for external beam
      radiation. However, no development of hypertension, proteinuria, or significant
      changes in serum creatinine or creatinine clearance were observed in our patients
      including 2 patients who received 106 and 113 GBq [(111)In-DTPA(0)]octreotide
      without protection with amino acids, over a follow-up period of respectively 3
      and 2 years. These findings show that the radiation of the short-range (maximal
      10 microns) Auger electrons originating from the cells of the proximal tubules is
      not harmful for the renal function. The decrease in serum inhibin B and
      concomitant increase of serum FSH levels in men indicate that the spermatogenesis
      was impaired.

PMID- 11965607
TI  - Indium-111-pentetreotide prolongs survival in gastroenteropancreatic
      malignancies.
AB  - Somatostatin and its analogues bind to somatostatin receptors (sst) 1 through 5
      that are overexpressed in neuroendocrine neoplasms such as gastroenteropancreatic
      (GEP) malignancies. After ligand-receptor binding, a fraction of the ligand
      receptor complexes internalize. This internalization process is an effective
      means of delivering cytotoxic radiolabeled somatostatin analogues, especially
      those emitting short-range decay particles such as Auger electrons, to the
      neoplastic cell nucleus. Indium-111-pentetreotide, an sst 2 preferring
      somatostatin analogue with gamma and Auger electron decay characteristics, is
      commonly used for the scintigraphic evaluation and management of neuroendocrine
      cancer patients. This clinical trial was performed to determine the effectiveness
      and tolerability of therapeutic doses of (111)In-pentetreotide in patients with
      GEP tumors. GEP tumor patients who had failed all forms of conventional therapy,
      with worsening of tumor-related signs and symptoms and/or radiographically
      documented progressive disease, an expected survival less than 6 months, and sst
      positivity as determined by the uptake on a 6.0 mCi (111)In-pentetreotide scan
      (OctreoScan; Mallinckrodt Medical, Inc, St. Louis, MO), were treated with at
      least 2 monthly 180-mCi intravenous injections of (111)In-pentetreotide. Baseline
      clinical assessments, serum chemistries, and plasma pancreastatin levels were
      measured and repeated before each (111)In-pentetreotide treatment. From February
      1997 to February 1998, 27 GEP (24 carcinoid neoplasms with carcinoid syndrome and
      3 pancreatic islet cells) patients were accrued, with 26 patients evaluable for
      clinical and radiographic responses, 21 patients evaluable for biochemical
      assessments, and 27 patients evaluable for survival analysis and safety. Toxicity
      was evaluated by using standard National Cancer Institute (NCI) Common Toxicity
      Criteria guidelines. Clinical benefit occurred in 16 (62%) patients.
      Pancreastatin levels decreased by 50% or more in 81% of the patients. Objective
      partial radiographic responses occurred in 2 (8%) patients, and significant tumor
      necrosis (defined by 20 Hounsfield units or greater decrease from baseline)
      developed in 7 (27%) patients. The following transient Grades 3/4 NCI Common
      Toxicity Criteria side effects were observed, respectively: leukocyte: 1/1;
      platelets: 0/2; hemoglobin: 3/0; bilirubin: 1/3; creatinine: 1/0; neurologic:
      1/0. Myeloproliferative disease and/or myelodysplastic syndrome have not been
      observed in the 6 patients followed-up for 48+ months. The median survival was 18
      months (range, 3-54+ mo). Two doses (180 mCi) of (111)In-pentetreotide are safe,
      well-tolerated, and improve symptoms in 62% of patients, decrease hormonal
      markers in 81% of patients, decrease Hounsfield units on computed tomography (CT)
      scans in 27% of patients, with 8% partial radiographic responses and increased
      expected survival in GEP cancer patients with somatostatin receptor-expressing
      tumors. The maximal tolerated dose of (111)In-pentetreotide and the optimal
      dosing schedules remain under investigation.

PMID- 11965608
TI  - Somatostatin receptor-targeted radionuclide therapy of tumors: preclinical and
      clinical findings.
AB  - In preclinical studies in rats we evaluated biodistribution and therapeutic
      effects of different somatostatin analogs, [(111)In-DTPA]octreotide, [(90)Y
      DOTA,Tyr(3)]octreotide and [(177)Lu-DOTA,Tyr(3)]octreotate, currently also being
      applied in clinical radionuclide therapy studies. [Tyr(3)]octreotide and
      [Tyr(3)]octreotate, chelated with DTPA or DOTA, both showed high affinity binding
      to somatostatin receptor subtype 2 (sst(2)) in vitro. The radiolabelled compounds
      all showed high tumor uptake in sst(2)-positive tumors in vivo in rats, the
      highest uptake being reached with [(177)Lu-DOTA,Tyr(3)]octreotate. In preclinical
      therapy studies in vivo in rats, excellent, dose dependent, tumor size responses
      were found, responses appeared to be dependent on tumor size at therapy start.
      These preclinical data showed the great promise of radionuclide therapy with
      radiolabelled somatostatin analogues. They emphasised the concept that especially
      the combination of somatostatin analogs radiolabeled with different
      radionuclides, like (90)Y and (177)Lu, is most promising to reach a wider tumor
      size region of high curability. Furthermore, different phase I clinical studies,
      using [(111)In-DTPA]octreotide, [(90)Y-DOTA,Tyr(3)]octreotide or [(177)Lu-DOTA,
      Tyr(3)]octreotate are described. Fifty patients with somatostatin receptor
      positive tumors were treated with multiple doses of [(111)In-DTPA(0)]octreotide.
      Forty patients were evaluable after cumulative doses of at least 20 GBq up to 160
      GBq. Therapeutic effects were seen in 21 patients: partial remission in 1
      patient, minor remissions in 6 patients, and stabilization of previously
      progressive tumors in 14 patients. The toxicity was generally mild bone marrow
      toxicity, but 3 of the 6 patients who received more than 100 GBq developed a
      myelodysplastic syndrome or leukemia. Radionuclide therapy with [(90)Y
      DOTA,Tyr(3)]octreotide started in 3 different phase I trials. Overall,
      antimitotic effects have been observed: about 20% partial response and 60% stable
      disease (N = 92) along with complete symptomatic cure of several malignant
      insulinoma and gastrinoma patients. Maximum cumulative [(90)Y
      DOTA,Tyr(3)]octreotide dose was about 26 GBq, without reaching the maximum
      tolerable dose. New is the use of [(177)Lu-DOTA,Tyr(3)]octreotate, which shows
      the highest tumor uptake of all tested octreotide analogs so far, with excellent
      tumor-to-kidney ratios. Radionuclide therapy with this analog in a phase 1 trial
      started recently in our center in 63 patients (238 administrations), Interim
      analysis of 18 patients with neuroendocrine tumors was performed very recently.
      According to the WHO, toxicity criteria no dose limiting toxicity was observed.
      Minor CT-assessed tumor shrinkage (25% - 50% reduction) was noticed in 6% of 18
      patients and partial remission (50% - 100% reduction, SWOG criteria) in 39%.
      Eleven percent of patients had tumor progression and in 44% no changes were seen.
      These data show that radionuclide therapy with radiolabelled somatostatin
      analogs, like [DOTA, Tyr(3)]octreotide and [DOTA, Tyr(3)octreotate is a most
      promising new treatment modality for patients who have sst(2)-positive tumors.

PMID- 11965609
TI  - Receptor-mediated radiotherapy with Y-DOTA-DPhe-Tyr-octreotide: the experience of
      the European Institute of Oncology Group.
AB  - High concentrations of subtype 2 somatostatin tumor receptors (sst(2)) are
      expressed in numerous tumors, enabling primary and metastatic masses to be
      localized by scintigraphy after injecting (111)In-labeled somatostatin analogue
      octreotide. In addition to neuroendocrine tumors, somatostatin receptors have
      been identified on cancers of the central nervous system, breast, lung, and
      lymphatic tissue, and the use of radionuclide-labeled somatostatin analogues
      appeared promising for therapy as well as for diagnosis of such malignancies. The
      somatostatin analogue [DOTA-(D)Phe(1)-Tyr(3)] octreotide (DOTATOC) possesses
      favorable characteristics for its potential therapeutic use in that it shows high
      affinity for sst(2), moderately high affinity for sst(5), and intermediate
      affinity for sst(3), high hydrophilicity, stable and facile labeling with (111)In
      and (90)Y. We began to investigate the potential therapeutic applications of
      (90)Y DOTATOC in 1997 by performing a thorough dosimetric study in 18 patients
      who were administered (111)In DOTATOC to estimate the absorbed doses during(90)Y
      DOTATOC therapy. Then, we moved on and treated an overall number of 256 patients,
      mostly recruited in 2 distinct protocols with and without the administration of
      kidney protecting agents, with (90)Y DOTATOC. No major acute reactions were
      observed up to the activity of 5.55 GBq per cycle. The MTD per cycle was defined
      as 5.18 GBq. Objective therapeutic responses were documented in more than 20% of
      patients in terms of partial and complete responses. The present article reports
      in details our clinical experience (still ongoing) and outcomes with the use of
      (90)Y DOTATOC.

PMID- 11965610
TI  - In- and Y-DOTA-lanreotide: results and implications of the MAURITIUS trial.
AB  - The high-level expression of somatostatin receptors (SSTR) on various tumor cells
      has provided the molecular basis for successful use of radiolabeled peptide
      analogues as tumor tracers in nuclear medicine. The vast majority of human tumors
      seem to overexpress one or the other of 5 distinct hSSTR subtype receptors.
      Whereas neuroendocrine tumors frequently overexpress human(h) SSTR2, intestinal
      adenocarcinomas frequently express hSSTR3 or hSSTR4, or both of these hSSTRs. In
      contrast to (111)In-diethylenetriamine pentaacetic acid (DTPA)-(D)he(1)
      octreotide (OctreoScan; Mallinckrodt, Petten, NL), which binds to hSSTR2 and 5
      with high affinity (K(d)0.1-5 nmol/L), to hSSTR3 with moderate affinity (K(d)10
      100 nmol/L), and does not bind to hSSTR1 and hSSTR4, (111)In /(90)Y-DOTA
      lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to
      hSSTR1 with lower affinity (K(d)200 nmol/L). Based on its unique hSSTR binding
      profile, (111)In-DOTA-lanreotide was suggested to be a potential radioligand for
      tumor diagnosis, and (90)Y-DOTA-lanreotide suitable for receptor-mediated
      radionuclide therapy. When directly compared with (111)In-DTPA-(D)he(1)
      octreotide and (111)In-DOTA-(D)he(1)-Tyr(3)-octreotide, discrepancies in the
      scintigraphic imaging pattern are seen in about one third of tumor patients
      concerning both the tumor uptake as well as the detection of tumor lesions. On a
      molecular level, these discrepancies seem to be based on a higher high-affinity
      binding affinity of (111)In-DOTA-(D)he(1)-Tyr(3)-octreotide for hSSTR2 (K(d)0.1-1
      nmol/L). Beneficial results of receptor-mediated experimental radionuclide
      therapy were first reported for high-dose treatment with (111)In-DTPA-(D)he(1)
      octreotide, based on the emission of Auger electrons. Phase IIa of the
      Multicenter Analysis of a Universal Receptor Imaging and Treatment Initiative, a
      European Study (MAURITIUS), shows in progressive cancer patients (therapy entry
      criteria) with a calculated tumor dose > 10 Gy/GBq (90)Y-DOTA-lanreotide, the
      proof-of-principle for treating tumor patients with peptide receptor imaging
      agents. In the MAURITIUS study, cumulative treatment doses up to 232 mCi (90)Y
      DOTA-lanreotide were given as short-term intravenous infusion. Preliminary
      treatment results in 154 patients indicate stable tumor disease in 41% (63 of
      154) of patients and regressive tumor disease in 14% (22 of 154) of tumor
      patients with different tumor entities expressing hSSTR. No severe acute or
      chronic hematologic toxicity, change in renal or liver function parameters caused
      by (90)Y-DOTA-lanreotide treatment were reported for patients in the MAURITIUS
      trial. In two thirds of patients with neuroendocrine tumor lesions, (90)Y-DOTA
      (D)he(1)-Tyr(3)-octreotide showed a higher tumor uptake and should therefore be
      considered the first choice for experimental receptor-based therapy. Potential
      indications for (90)Y-DOTA-lanreotide treatment are radioiodine-negative thyroid
      cancer, hepatocellular cancer, lung cancer, some brain tumors, and possibly
      melanomas. In conclusion, preclinical data and clinical studies confirm the
      potential usefulness of radiolabeled lanreotide for tumor diagnosis and therapy.
      However, careful consideration of the type of radiotracer used for receptor
      mediated therapy should be made for the individual patient. Whole-body dosimetry
      should always be performed to predict doses for tumors and the critical organs,
      which are kidney and bone marrow.

PMID- 11965611
TI  - [Collected papers devoted to the celebration of the 85th birthday of Professor
      Jaromir Korcak].

PMID- 11965612
TI  - Fertility variation among the U.S. foreign stock population in 1900

PMID- 11965613
TI  - Possible approaches to improving the international comparability of immigration
      and emigration statistics:  an illustration of the Canadian situation
AB  - "This article seeks to highlight the extent of the lack of standardization which
      exists in the field of international migration statistics and, using statistics
      for Canada as an example, to illustrate how significant progress towards
      resolving this problem could be made if sufficient numbers of countries made
      their immigration and emigration statistics gradually comply more fully with the
      United Nations recommendations."

PMID- 11965614
TI  - Benefits of migration as a personal strategy in Nazare, Portugal.
AB  - "This article analyzes the causes, patterns and results of involvement in
      international wage labor migration for Nazare, a Portuguese fishing village and
      tourist resort.  Some migrate permanently, others return to invest locally, and
      yet others only work abroad part of each year.  Data indicate that international
      migration is a successful strategy for coping with a restrictive local
      opportunity structure.  International migrants have more income, savings, capital
      goods, consumer goods and automobiles than non-migrants or those who only migrate
      within Portugal."

PMID- 11965615
TI  - Moral consensus in bioethics: illusive or just elusive?

PMID- 11965616
TI  - Making sense of consensus: responses to Engelhardt, Hester, Kuczewski, Trotter,
      and Zoloth.

PMID- 11965618
TI  - Bibliography. Current world literature. Developmental disorders.

PMID- 11965617
TI  - The eyes have it...

PMID- 11965619
TI  - Bibliography. Current world literature. Seizure disorders.

PMID- 11965620
TI  - [Surprising ventricular fibrillation].

PMID- 11965621
TI  - [Prolonged itching of anus].

PMID- 11965623
TI  - Fracture healing. What it takes to heal a break.

PMID- 11965624
TI  - Health tips. Hot vs. cold treatment.

PMID- 11965622
TI  - Stroke. Often predictable, often preventable.

PMID- 11965625
TI  - Blood pressure drug may prevent diabetes in some people.

PMID- 11965626
TI  - Sprouts linked to E. coli, salmonella.

PMID- 11965627
TI  - Palliative care. A better end of life.

PMID- 11965628
TI  - AIDS in older people. A hidden problem.

PMID- 11965629
TI  - Sarcopenia. A matter of muscle.

PMID- 11965630
TI  - My husband recently had coronary bypass surgery. His heart function has improved
      and we're thankful, but he has a scar on his chest that's very thick and
      unsightly. Is there a way to treat the scar?

PMID- 11965631
TI  - Pulmonary hypertension. High blood pressure in the lungs.

PMID- 11965632
TI  - Health tips. Help your skin weather the winter.

PMID- 11965633
TI  - Implantable middle ear hearing device now available.

PMID- 11965634
TI  - Carpal tunnel syndrome. Make way for relief.

PMID- 11965635
TI  - The spleen. Behind your ribs, behind the scenes.

PMID- 11965636
TI  - Generic drugs. Understanding their value.

PMID- 11965637
TI  - Second opinion. A friend gave me a brochure for a product that claimed it has
      absolutely no side effects because it is all natural. Is that possible?

PMID- 11965638
TI  - Second opinion. I want to start an exercise program, but I'm afraid it may cause
      too much wear and tear on my knees. Should I be concerned?

PMID- 11965639
TI  - Survey finds RN turnover rate of 21.3%.

PMID- 11965640
TI  - Biliary ascariasis with acute hemorrhagic pancreatitis: a case report.
AB  - A case of acute hemorrhagic pancreatitis associated with biliary ascariasis in a
      35 year old man is reported. Clinical presentation and laboratory investigation
      along with management outcome are discussed.

PMID- 11965641
TI  - Solitary fibrous tumour of the parotid gland.

PMID- 11965642
TI  - A case-control study of the association between socio-demographic, lifestyle and
      medical history factors and multiple sclerosis.
AB  - OBJECTIVE: The etiology of multiple sclerosis (MS) remains poorly understood.
      Socio-demographic characteristics may play important roles in its development.
      METHODS: In a case-control study of MS, a total of 200 newly diagnosed MS
      patients and 202 frequency age- and sex-matched controls were studied. RESULTS: A
      direct and significant association was observed between cigarette smoking and the
      risk of MS. Higher education seemed to reduce the risk of MS. Contact with cats
      was inversely associated with MS, particularly in males, whereas contact with
      caged birds increased the risk significantly, especially in females. A strong
      family aggregation of MS was observed among cases. A past history of trauma and
      eye problems appeared to pose a high risk of MS. Cases had a significant family
      history of eye problems, mumps, measles, rubella, cancer and auto-immune
      diseases. CONCLUSION: If smoking and history of certain infectious diseases
      increase the risk of MS significantly, they could be modified and avoided,
      thereby reducing the likelihood of being afflicted by MS.

PMID- 11965644
TI  - Price survey. Suture prices headed down.

PMID- 11965645
TI  - Growing pains: glitches mark new MMI systems.

PMID- 11965643
TI  - [The parasite capacity of the host population].
AB  - The estimation of parasitic pressure on the host populations is frequently
      required in parasitological investigations. The empirical values of prevalence of
      infection are used for this, however the latter one as an estimation of parasitic
      pressure on the host population is insufficient. For example, the same prevalence
      of infection can be insignificant for the population with high reproductive
      potential and excessive for the population with the low reproductive potential.
      Therefore the development of methods of an estimation of the parasitic pressure
      on the population, which take into account the features the host population, is
      necessary. Appropriate parameters are to be independent on view of the
      researcher, have a clear biological sense and be based on easily available
      characteristics. The methods of estimation of parasitic pressure on the host at
      the organism level are based on various individual viability parameters:
      longevity, resistance to difficult environment etc. The natural development of
      this approach for population level is the analysis of viability parameters of
      groups, namely, the changing of extinction probability of host population under
      the influence of parasites. Obviously, some critical values of prevalence of
      infection should exist; above theme the host population dies out. Therefore the
      heaviest prevalence of infection, at which the probability of host population
      size decreases during the some period is less than probability of that increases
      or preserves, can serve as an indicator of permissible parasitic pressure on the
      host population. For its designation the term "parasite capacity of the host
      population" is proposed. The real parasitic pressure on the host population
      should be estimated on the comparison with its parasite capacity. Parasite
      capacity of the host population is the heaviest possible prevalence of infection,
      at which, with the generation number T approaching infinity, there exists at
      least one initial population size ni(0) for which the probability of size
      decrease through T generations is less than the probability of its increase.
      [formula: see text] The estimation of the probabilities of host population size
      changes is necessary for the parasite capacity determination. The classical
      methods for the estimation of extinction probability of population are unsuitable
      in this case, as these methods require the knowledge of population growth rates
      and their variances for all possible population sizes. Thus, the development
      methods of estimate of extinction probability of population, based on the using
      of available parameters (sex ratio, fecundity, mortality, prevalence of infection
      PI) is necessary. The population size change can be considered as the Markov
      process. The probabilities of all changes of population size for a generation in
      this case are described by a matrix of transition probabilities of Markov process
      (pi) with dimensions Nmax x Nmax (maximum population size). The probabilities of
      all possible size changes for T generations can be calculated as pi T. Analyzing
      the behaviour matrix of transition at various prevalence of infection, it is
      possible to determine the parasite capacity of the host population. In
      constructing of the matrix of transition probabilities, should to be taken into
      account the features the host population and the influence of parasites on its
      reproductive potential. The set of the possible population size at a generation
      corresponds to each initial population size. The transition probabilities for the
      possible population sizes at a generation can be approximated to the binomial
      distribution. The possible population sizes at a generation nj(t + 1) can be
      calculated as sums of the number of survived parents N1 and posterities N2; their
      probabilities--as P(N1) x P(N2). The probabilities of equal sums N1 + N2 and nj(t
      + 1) > or = Nmax are added. The number of survived parents N1 may range from 0 to
      (1-PI) x ni(t). The survival probabilities can be estimated for each N1 as
      [formula: see text] The number of survived posterities N2 may range from 0 to
      N2max (the maximum number of posterities). N2max is [formula: see text] and the
      survival probabilities for each N2, is defined as [formula: see text] where
      [formula: see text], ni(t) is the initial population size (including of males and
      infected specimens of host), PI is the prevalence of infection, Q1 is the
      survival probabilities of parents, Pfemales is the frequency of females in the
      host population, K is the number of posterities per a female, and Q2 is the
      survival probabilities of posterities. When constructing matrix of transition
      probabilities of Markov process (pi), the procedure outlined above should be
      repeated for all possible initial population size. Matrix of transition
      probabilities for T generations is defined as pi T. This matrix (pi T) embodies
      all possible transition probabilities from the initial population sizes to the
      final population sizes and contains a wealth of information by itself. From the
      practical point of view, however, the plots of the probability of population size
      decrease are more suitable for analysis. They can be received by summing the
      probabilities within of lines of matrix from 0 to ni--1 (ni--the population size,
      which corresponds to the line of the matrix). Offered parameter has the number of
      advantages. Firstly, it is independent on a view of researcher. Secondly, it has
      a clear biological sense--this is a limit of prevalence, which is safe for host
      population. Thirdly, only available parameters are used in the calculation of
      parasite capacity: population size, sex ratio, fecundity, mortality. Lastly, with
      the availability of modern computers calculations do not make large labour.
      Drawbacks of this parameter: 1. The assumption that prevalence of infection,
      mortality, fecundity and sex ratio are constant in time (the situations are
      possible when the variability of this parameters can not be neglected); 2. The
      term "maximum population size" has no clear biological sense; 3. Objective
      restrictions exist for applications of this mathematical approach for populations
      with size, which exceeds 1000 specimens (huge quantity of computing operations-
      order Nmax 3*(T-1), work with very low probabilities). The further evolution of
      the proposed approach will allow to transfer from the probabilities of size
      changes of individual populations to be probabilities of size changes of
      population systems under the influence of parasites. This approach can be used at
      the epidemiology and in the conservation biology.

PMID- 11965646
TI  - Why hospitals aren't rushing into e-commerce.

PMID- 11965647
TI  - Creutzfeldt-Jacob disease (CJD): report of 10 cases from North India.

PMID- 11965648
TI  - Germinoma of the basal ganglia: a case report and review of literature.
AB  - Germs cell tumors of extrapineal region are extremely uncommon. The
      clinicopathological features of germinoma in the basal ganglia, in a 21 year old
      male are presented in this report. Post-operative radiotherapy is advocated, in
      view of the good radiosensitivity of these tumors.

PMID- 11965649
TI  - [Cracow medical press in the time of foreign domination in Poland (1795-1918) in
      the light of statistic analysis].
AB  - In the years 1795-1918 thirty-one periodicals dedicated to medicine and health
      resorts were issued. The "Annual report of issues and activities of the surgical
      and obstetrical clinic of the Jagiellonian University" [Rocznik obejmujacy zdanie
      spraw i czynnosci kliniki chirurgicznej i polozniczej Uniwersytetu
      Jagiellonskiego] (1831-1834) was the first one and it was followed by the "Cracow
      Pharmaceutical Memoirs" [Pamietnik Farmaceutyczny Krakowski] (1834-1836). An
      average period of existence of Cracow medical journals and papers was 6.3 years
      and was nearly twice as long as an average period calculated for the whole Cracow
      press. It is a very interesting phenomenon as we are speaking about periodicals,
      which - because of their content - could not be so widely read and could not have
      such a big circulation, as very popular "Czas" [Time] or "Illustrowany Kuryer
      Codzienny" [Illustrated Daily Courier]. Among the medical press we can find 4
      papers and 27 periodicals. There appeared also 3 medical calendars in Cracow. The
      medical periodicals were as follows: three weekly magazines (11.1%), ten
      fortnightly publications (37%), six monthly magazines (22.2%), two quarterlies
      (7.3%) and six annuals (22.2%). The four daily St. papers were issued for a very
      short time and had a specific character as these publications were prepared on
      the occasion of medical and scientific conferences held in Cracow. Taking into
      consideration content of the published information we can divide the Cracow
      medical press into: general medical titles (12 publications - 38.7%), periodicals
      dedicated to widely comprehended popularization of health and hygiene (5
      publications - 16.1%), specialist periodicals related to detailed branches of
      medical knowledge (5 publications - 16.1%), pharmaceutical journals (2 titles -
      6.5%) and publications on balneology, health resorts and nursing homes in Galicia
      (7.22%). From among 47 journalists working in the Cracow medical press and
      performing functions of editor, editor-in-chief or publisher only three persons
      had not medical education and three other persons have not been identified. So,
      41 (87.2%) editors and publishers of the Cracow medical press had university
      level medical education; five of them were pharmacists and 36 (97.3%) medical
      doctors. Mainly natural persons were editors of the medical magazines. Only in
      five (16.1 %) cases legal persons were responsible for publications. Instead,
      legal persons dominated among publishers - 17 titles (54.8%).

PMID- 11965650
TI  - [The first Polish report on congenital diaphragmatic hernia and visceral
      malrotations].
AB  - The forgotten throughout the years the doctor dissertation from 1837 of the
      Polish physician Ludwik Przybylko entitled De pravo organorum situ ("About
      malposition of the human organs") was presented. This paper, excessively modern
      in its epoch, contains the compendium of the contemporary medical science of the
      organs' dislocation and malrotation (including heart malposition and coexisting
      defects). First of all, however, it is the well-scientifically documented case
      report on the diaphragmatic hernia in the newborn. The summarized historical
      review of scientific report on diaphragmatic hernia places a special emphasis on
      the reports that had been published before the dissertation of Przybylko and
      before the Bochdalek's historical report in 1848, since then the posterolateral
      defects of the diaphragm have been defined with that name. The extensive
      fragments of the dissertation translated from Latin into Polish have been cited.
      Ludwik Przybylko presented not only the clinical report and details of precise
      anatomopathological description of the newborn with diaphragmatic hernia, but he
      also cited the relevant literature and discussed the issue with thorough
      knowledge. Numerous clinical and anatomopathological remarks of the author, based
      on his own experience and accordingly applied literature, have been current until
      today. The case report is completed with four engraved illustrations (woodcut)
      that document the autopsy examination. The work contains extremely interesting
      and revolutionary for that time considerations on the evolution (22 years prior
      to the famous work of Darwin) with an attempt to locate the etiology of
      congenital diaphragmatic hernia in the evolution. The authors of this paper
      suggest that the dissertation of Ludwik Przybylko should be interesting for
      paediatric surgeons and, especially because of its unusual and original contents,
      ought to take constant place in the history of Polish and world's medicine.

PMID- 11965651
TI  - From the Centers for Disease Control and Prevention. Progress toward global
      eradication of poliomyelitis, 2001.

PMID- 11965652
TI  - From the Centers for Disease Control and Prevention. Reporting of laboratory
      confirmed chlamydial infection and gonorrhea by providers affiliated with three
      large managed care organizations--United States, 1995-1999.

PMID- 11965653
TI  - JAMA patient page. Blood donation.

PMID- 11965654
TI  - Effects of experimental hypogravity on peroxidase and cell wall constituents in
      the dwarf marigold.
AB  - Dwarf Marigolds grown from seed under experimental hypogravity are modified in
      lignin content, hemicellulose composition, and peroxidase activity. The two
      conditions used, clinostats and flotation, induced changes differing in magnitude
      but qualitatively similar. Most responses on clinostats required corrections for
      vertical axis rotational effects, thus limiting the value of these instruments in
      free-fall simulation. These findings extend earlier observations suggesting that
      increased peroxidase and decreased lignin are characteristic of growth under
      experimental hypogravity.

PMID- 11965655
TI  - Comparative study of lesions in the brain of rats exposed to heavy ions:
      accelerator and stratospheric flight research.
AB  - Irradiations of rat's brain with heavy ionized particles (12/6C, 291 Mev/nucleon,
      100 to 300 ions/mm2) have been carried out at the Lawrence Berkeley Laboratory.
      Exposures were made with slowed ions which stopped within the brain as well as
      with more energetic particles which passed through. Histological examination of
      irradiated encephalons by optical microscopy showed zones of glial reaction and
      an increased number of darkly staining cells. By electron microscopy,
      intercellular edema, various alterations of nervous cells and macrophagy were
      observed, especially with stopped ions.

PMID- 11965656
TI  - Radiobiological investigations in Cosmos 782 space flight (Biobloc SF1
      experiment).
AB  - Several biological objects were flown in Cosmos 782 in order to investigate the
      effects of HZE cosmic particles and other environmental factors of space. Space
      flight results in chromosomic aberrations in lettuce seeds, decreased germination
      rate and increased frequency of abnormalities in tobacco seeds and decreased
      developmental capacity in Artemia eggs. In lettuce and tobacco seedlings, changes
      were observed not only in seeds hit by heavy ions but also in nonhit seeds. The
      results indicate that exposure to the space environment can induce important
      changes in biological objects and emphasize the usefulness of investigations
      carried out on organisms less complex than mammals.

PMID- 11965657
TI  - Biological study of tobacco seeds flown in the joint Apollo-Soyouz Test-Project.
AB  - A preliminary experiment was carried out in order to detect eventual effects
      attributable to primary and background cosmic radiations received by tobacco
      seeds during the joint Apollo-Soyouz space flight. No genetic effect was observed
      but several developmental and physiological alterations took place.

PMID- 11965658
TI  - Genetic effects of balloon flight in Drosophila melanogaster.
AB  - Drosophila males were flown in balloons and crossed, after recovery, in order to
      investigate possible genetic effects of cosmic rays. No significant effect was
      observed in the lethal and dominant mutation rate.

PMID- 11965659
TI  - Radiobiological results from the Bacillus subtilis Biostack experiments within
      the Apollo and the ASTP space flights.
AB  - In order to check the results of earlier Biostack experiments, new experimental
      techniques were developed for the Biostack III experiment in the Apollo-Soyuz
      test project (ASTP). These techniques resulted in an increased accuracy of
      localization down to 0.2 micrometers for the determination of the impact
      parameter, accompanied by an increase in the sample size available for biological
      investigation. In addition, colony forming ability, metabolic mutations, and
      mutations affecting UV- and x-ray sensitivity were rendered observable by these
      methods. The biological and physical results obtained so far from the evaluation
      of the Bacillus subtilis experiment within Biostack III confirm and extend the
      findings of the previous Biostack experiments. They also add to the questions
      about the mechanisms of action of the radiation field under investigation, since
      the observed effects cannot be interpreted in terms of standard concepts.

PMID- 11965661
TI  - Planetary protection guidelines for outer planet missions.
AB  - Facilities, techniques, and operational procedures used to implement Planetary
      Protection (PP) requirements for the Viking Project are reviewed in order to
      better define the COSPAR resolution which proposes that Outer Planet spacecraft
      be assembled using Viking-like clean room technology. It is concluded that, for
      such missions, PP requirements can be met by adopting Viking clean room
      standards, personnel and operation procedures, and by establishing PP as an
      official entity in project management.

PMID- 11965660
TI  - The chemical activities of the Viking biology experiments and the arguments for
      the presence of superoxides, peroxides, gamma-Fe2O3 and carbon suboxide polymer
      in the Martian soil.
AB  - The evolution of N2, Ar, O2, and CO2 from Martian soil as a function of humidity
      in the Gas Exchange Experiment are correlated with the mean level of water vapor
      in the Martian atmosphere. All but O2 are associated with desorption. The
      evolution of oxygen is consistent with the presence of alkaline earth and alkali
      metal superoxides; and their peroxides and the gamma-Fe2O3 in the soil can
      account for the generation of radioactive gas in the Labeled Release Experiment.
      The slower evolution of CO2 from both the Gas Exchange Experiment and the Labeled
      Release Experiment are associated with the direct oxidation of organics by gamma
      Fe2O3. The Pyrolytic Release Experiment's second peak may be carbon suboxide as
      demonstrated by laboratory experiments. A necessary condition is that the polymer
      exists in the Martian soil. We ascribe the activity of the surface samples to the
      reaction of Martian particulates with an anhydrous CO2 atmosphere activated by uv
      and ionizing radiations. The surface particles are ultimately altered by exposure
      to small but significant amounts of water at the sites. From the working model,
      we have predicted the peculiar nature of the chemical entities and demonstrated
      that the model is justified by laboratory data. The final confirmation of this
      model will entail a return to Mars, but the nature and implications of this
      chemistry for the Martian surface is predicted to reveal even more about Mars
      with further simulations in the laboratory.

PMID- 11965662
TI  - Effects of gravitational and magnetic fields on transplanted neuroblastoma
      vascularity.
AB  - Transplanted neuroblastomas were subjected to altered neural influences and
      imposed gravitational and magnetic fields, either separately or in combination.
      In each case impaired vascularity, and greater extravasation of blood with
      associated tumor necrosis occurred in the experimental animals. The combination
      of both hypergravity and alternating magnetic field resulted in definite
      macroscopic but less marked microscopic changes than with either force alone.
      Neuroblastoma cells in vitro exposed to a magnetic field showed no definite
      growth changes, suggesting an effect of the field forces on the host. Exposure of
      a unicellular organism, not requiring a host for survival, to a similar magnetic
      field, did result in distinct cell division changes.

PMID- 11965663
TI  - Changes in the body composition of monkeys during long-term exposure to high
      acceleration fields.
AB  - Adult, 10-14 kg, male pig-tailed monkeys (Macaca nemestrina) were subjected to
      continuous centrifugation for 7 months in acceleration fields up to 2.5 g.
      Several major parameters of body composition, body-fluid distribution, and
      hematology were evaluated at various levels of high g by in vivo analytical
      techniques. Statistically significant decreases in total body mass, lean body
      mass, total body water, extracellular water content and interstitial water
      content proportional to the level of high g were also demonstrated. Body cell
      mass, total body fat, dry body mass, lean body solids, and red cell volume did
      not change significantly. Significant decreases in red cell count, blood
      hemoglobin level and venous hematocrit value accorded with the plasma volume and
      red cell volume findings. Total plasma protein concentration did not change
      significantly. The results indicate a substantial loss of total body mass in the
      form of body water. The loss apparently occurred from the interstitial spaces of
      the body in the face of a sizeable increase in plasma volume. Physiological
      significance of the body composition and fluid distribution changes at high g is
      discussed and compared to the changes described for astronauts at low g. Current
      theory of fluid-balance physiology favors the concept that interstitial volume
      and blood volume are tightly coupled and change in the same direction. However,
      it appears that the changes which occur where the ambient acceleration field is
      varied may represent an exception to the general hypothesis for the regulation of
      the extracellular fluid volume.

PMID- 11965664
TI  - Thermoregulatory responses of unanesthetized rats exposed to gravitational fields
      of 1 to 4g.
AB  - Rats exposed to 2g environments (achieved by centrifugation) exhibit a decreased
      ability to maintain colonic temperature (Tco) when challenged with a 1 hr drop in
      ambient temperature (Ta). As an extension of this work the present study
      considers whether the altered ability to maintain Tco is proportional to the
      magnitude of the acceleration field in the range from 1g-4g, and whether the
      magnitude of the decreased thermoregulatory ability is related to the onset time
      of the temperature drop relative to that of the acceleration. Male, Sprague
      Dawley rats were instrumented on the experimental day with thermistors for
      measuring Tco. The unanesthetized rat was then placed in a plexiglas chamber,
      positioned on a centrifuge 1.37 m in radius, and exposed to 1.5, 2, 2.5, 3, 3.5,
      or 4g for 5-7 hrs. The exposure to reduced temperature (Ta = approximately 7
      degrees C) for 1 hr began 3 hrs after initiation of centrifugation. These
      experiments indicated that the magnitude of the cold-induced drop in Tco was
      linearly related to the acceleration field. The effect of a specific stressor
      (cold) on the thermoregulatory system is therefore a direct function of the
      gravitational field.

PMID- 11965665
TI  - The roles of body mass and gravity in determining the energy requirements of
      homoiotherms.
AB  - Studies by Kleiber and by Brody in the 1930's established the 3/4 power of body
      weight as the unit for comparison of metabolic phenomena in homoiotherms. Later
      Kleiber conceived of the energy requirement as a composite function, with a
      thermoregulatory component, proportional to heat loss, and an antigravity
      component that is directly proportional to body weight. Maintenance feed
      requirements have been measured with groups of small animals chronically exposed
      to several acceleration fields. Analysis of the results leads to an arithmetic
      relationship between the maintenance requirement and acceleration field strength:
      Fg = Fo+k g Where: F is the maintenance feed requirement (Fg in field of g
      strength, and Fo where g=0); and, g is the ambient acceleration field strength.
      When the equations are compared for groups of different body size, Fo tends to
      vary between the 0.4 and 0.5 power of body mass--and k tends to be the same,
      irrespective of body mass (BM). These findings tend to confirm the Kleiber
      concept of a composite nature of homoiotherm maintenance requirements.

PMID- 11965666
TI  - Geotropism of hornet comb construction under persistent acceleration.
AB  - Social wasps (Vespinae) are insects which build in a precise geotactical
      orientation. The effect of persistent acceleration on comb construction by
      Oriental hornet (Vespa orientalis) workers was assessed experimentally within
      breeding boxes of various size and shape. Groups of hornets at the building phase
      were subjected to a centrifugal and gravitational force with a resultant ranging
      between 26 degrees and 45 degrees. The comb construction within such boxes was
      compared to that within control boxes under ordinary gravitational pull. It was
      found that: a) juvenile hornets (1-2 days of age) placed in quasi-rectangular
      boxes built in the direction of the resultant force; b) juvenile and adult
      hornets (3-7 days of age) placed in spherical shaped containers also built in the
      direction of the resultant force; c) adult hornets who had spent their first days
      of life in a stationary rectangular box, apparently learned the direction of the
      gravitational force and "tried" to build in this direction when exposed to a
      centrifugal force; d) adult hornets made to spin in quasi-rectangular boxes
      tilted in the direction of the calculated resultant force built in the direction
      of the resultant. These results suggest that hornets learn the direction of the
      gravitational force during the first days of life and that geometrical cues
      within the breeding box enable them to build in the direction of the force to
      which they have become habituated. From the standpoint of geometric cues, only
      the roof of the breeding box is of critical importance.

PMID- 11965667
TI  - Life sciences and space research volume XVI. Proceedings of the Open Meetings of
      the Working Group on Space Biology of the Twentieth Plenary Meeting of COSPAR,
      Tel Aviv, Israel, 7-18 June 1977.

PMID- 11965668
TI  - Global alliance on vaccines and immunizations. Vaccine promotion is circumventing
      market forces.

PMID- 11965669
TI  - Fifth revision of Declaration of Helsinki. Ethics and money are not good
      bedfellows.

PMID- 11965670
TI  - First episode psychosis. GPs must assess patients' risk behaviour.

PMID- 11965671
TI  - Income inequality and population health. Hierarchy and health are related.

PMID- 11965672
TI  - Is ocean fertilization credible and creditable?

PMID- 11965673
TI  - Rock art revisited.

PMID- 11965674
TI  - Beauty, biological weapons, and Botox.

PMID- 11965675
TI  - Prospects for an AIDS vaccine.

PMID- 11965676
TI  - Astronaut-centered philosophy for designing manned space system.
AB  - Astronaut-centered design philosophy is a new concept suggested by the authors
      for manned space system design. It stems from human-centered design philosophy.
      Human-centered design means that human role is regarded as important basis and
      foundation for system design. At the beginning, the engineers used to adopt
      technology-centered philosophy for designing complex system, but much practice
      proved that the technology-centered design philosophy won't work, resulting in
      lower system safety and performance. So it has been currently replaced by human
      centered philosophy. As examples, the principles of human-centered automation of
      the International Civil Aviation Organization and NASA JSC's Human-rating
      Requirements were introduced. At last, the astronaut-centered design philosophy
      and its requirements were put forward by the authors. These requirements consist
      of: general requirements, man-machine interaction requirements, man-environment
      interaction requirements and interpersonal relationship requirements.

PMID- 11965677
TI  - [Effects of task load on early and late components of auditory event-related
      brain potentials].
AB  - OBJECTIVE: To study the effects of task load on early and late components of
      auditory event-related potentials. METHOD: The subjects were 12 healthy right
      handed volunteers aged 20-23 years. The stimuli were auditory signals of two
      kinds of tones and appeared randomly from four speakers located on the left
      front, left-rear, right-front and right-rear over the head of the subject. Tasks
      included: a) pressing the button in response to all signals (AR); b) making
      location discrimination to tones from left or right (DR); c) making location
      discrimination to target signals (T, high-tone or low-tone) from the four sides,
      and make no response to non-target signals (NT). The event-related potentials
      (ERPs) of three tasks were compared with each other. RESULT: 1) The early
      components include P1, N1 and P2, and the late components include N2 (N2a/N2b),
      P3 and SW (slow wave). 2) P1 wave amplitude increased with the increase of the
      task load. N1 wave amplitude of SR(T)-ERPs decreased markedly compared with that
      of AR-ERPs and DR-ERPs, and P2 wave amplitude of AR-ERPs increased significantly
      compared with that of DR-ERPs and SR(T)-ERPs. P2 wave latency shortened with
      increase of the task load. 3) N2 (N2a/N2b), P3 and SW wave amplitudes increased
      with the increase of the task load. CONCLUSION: These data indicate that not only
      the late components but also the early components of auditory event-related
      potentials were affected by task load. The effects on the late components may be
      related to the change of the early component (P1) which may reflect the early
      activity process of the brain.

PMID- 11965678
TI  - [Effects of repeated +Gz exposures on the expression of c-fos protein in rabbit
      brain].
AB  - OBJECTIVE: To investigate the effect of repeated +Gz exposures on the expression
      and distribution of c-fos protein immunoreactivity in rabbit brain. METHOD:
      Twenty rabbits were divided randomly into 4 groups (n=5 in each group). Animals
      were anesthetized and then exposed to +4 Gz until 30 s after the arterial
      pressure at eye level dropped to 0 kPa. The exposure was repeated for 3 times
      with 30 min intervals. The expression of c-fos protein in rabbit brain was
      examined at 0 h, 1 h and 6 h after +Gz exposure by immunohistochemistry method.
      RESULT: c-fos protein was obviously expressed in cortex, the third ventricle,
      hippocampus and dentate gyrus immediately after repeated +Gz exposures, and
      strongly expressed 1 h after the exposure, and then had a tendency to decrease 6
      h after the exposure. CONCLUSION: Three +Gz exposures may cause time-dependent c
      fos expression in rabbit brain, which may be involved in +Gz-induced brain
      damage.

PMID- 11965679
TI  - [Features of heart rate, blood pressure, heart rate variability and cerebral
      blood flow during sequential head-up tilt test].
AB  - OBJECTIVE: To investigate the features of BP, HR, cerebral blood flow (CBF) and
      heart rate variation (HRV) during sequential head-up tilt table test (HUT) and
      provide information for methodology of testing tendency to syncope in pilots.
      METHOD: Sixteen healthy male were exposed to HUT +45 degrees 20 min, +60 degrees
      20 min, and +75 degrees 20 min respectively with 5 min rests in between. CBFV,
      HR, HRV, BP were measured with transcranial doppler image (TCI), 12-Lead in phase
      ECG. RESULT: 1) As the tilt angle became larger, HR and DBP increased gradually
      (P<0.05), with SBP, PP and CBF Velocity (Vs,Vm,Vd) descended. There were
      significant differences among the various conditions. CV became smaller before
      +75 degrees, and then it began to increase. 2) Correlation between physiological
      indices and techno-indices were analyzed. At the point of 1 min, tilt angle was
      significantly positively correlated with SBP, DBP, MAP, Vd, and sdRR (P<0.01); At
      the point of 20 min, tilt angle was significantly positively correlated with HR
      and sdRR (P<0.01), but negatively correlated with SBP, PP, Vs and mRR (P<0.01),
      time of exposure was positively correlated with HP (P< 0.01), but negatively
      correlated with Vm, Vd, and mRR (P<0.01). 3) Correlation among physiological
      indices were also analyzed. HR were negatively correlated with SBP, Vs, Vm and Vd
      (P<0.01), SBP were significantly positively correlated with Vd, and mRR (P<0.01).
      Vs, Vm, Vd were significantly positively correlated with mRR and sdRR (P< 0.01).
      CONCLUSION: By investigating HR, BP, HRV and CBFV during of different angles,
      some advises for evaluating the tendency to syncope in pilots were put forward.

PMID- 11965680
TI  - [Effects of simulated weightlessness on the expression of cyclooxygenase-2 in rat
      calvarial osteoblasts induced by fluid shear stress].
AB  - OBJECTIVE: To investigate the effect of simulated weightlessness on
      mechanotransduction in rat calvarial osteoblasts. METHOD: Osteoblasts were
      isolated from neonatal rat calvariae and then were set to two groups. One was
      cultured in clinostat to simulate the weightlessness environment. Another was
      cultured in 1 G gravitational environment. After 60 h, osteoblasts were treated
      with 0.5 Pa or 1.5 Pa FSS in a flow chamber. The FSS treatment time was set to 30
      min and 60 min, respectively. The specimens of each group were obtained for
      immunohistochemistry staining and determination of expressions of cyclooxygenase
      2 (COX-2) in osteoblasts. RESULT: In osteoblasts cultured in 1 G gravitational
      environment, COX-2 expression was increased remarkably from 30 min to 60 min with
      the treatment of FSS (P<0.01). There was no clear difference between the
      expression of COX-2 after treatments of 0.5 Pa or 1.5 Pa FSS; In cells cultured
      in simulated weightlessness environment, no detectable expression of COX-2 was
      found with the treatment of 0.5 Pa FSS. The expression of COX-2 was only detected
      after 60 min treatment of 1.5 Pa FSS, but the level of expression was decreased
      significantly (P<0.01). CONCLUSION: These results demonstrated that the
      mechanotransduction in osteoblasts was down-regulated in simulated (correction of
      stimulated) weightlessness.

PMID- 11965681
TI  - [Effects of simulated weightlessness on ultrastructure of soleus muscle spindle
      in rats].
AB  - OBJECTIVE: To study changes in ultrastructure of soleus muscle spindle induced by
      simulated weightlessness in rats. METHOD: Weightlessness was simulated by tail
      suspension in female rats. The ultrastructure of isolated soleus muscle spindle
      were observed in 4 d, 7 d, 14 d tail-suspended and 14 d recovered rats. RESULT:
      Chaotic myofibril, hyperplasia of mitochondria, and enlargement of terminal
      cisterna were found in the ultrastructure of isolated soleus muscle spindle in 4
      d tail-suspended rats. The ultrastructure of isolated soleus muscle spindle in 7
      d tail-suspended rats showed more distinct changes, while that in 14 d tail
      suspended rats showed obvious retrograde changes. The ultrastructure of isolated
      muscle spindle in 14 d recovered rats after 14 d tail-suspension were similar to
      that of control group. CONCLUSION: Simulated weightlessness could induce time
      related and reversible changes in ultrastructure of soleus muscle spindle in
      rats.

PMID- 11965682
TI  - [Cardiovascular responses to G-suits with 3 levels of positive pressure breathing
      using different chest counter pressures].
AB  - OBJECTIVE: To observe cardiovascular responses to positive pressure breathing
      (PPB) using different counter pressures. METHOD: Cardiovascular responses of 7
      male healthy subjects (aged 18-20 years) wearing two kinds of Jerkin-G-suit were
      observed under three levels of ground-level PPB (30, 50, 70 mmHg) for 3 min.
      RESULT: All subjects completed the experiment successfully. While during PPB at
      50, 70 mmHg levels within 3 min, HR, MAP, TPR elevated significantly, while SV
      declined significantly. At all 3 PPB levels Q-Z time was not significantly
      changed. There were significant difference (P<0.05) between delta SV and delta
      TPR with the two Jerkin-G-suits under PPB of 70 mmHg. CONCLUSION: PPB resulted in
      elevation of MAP, TPR, HR and decline of SV significantly using two kinds of
      Jerkin-G-suit. PPB had no effect on contractile function of cardiac muscle. Under
      PPB, SV increased significantly when chest counter pressure was equal to the mask
      pressure.

PMID- 11965683
TI  - [+Gz protection of the on board oxygen generating system (OBOGS) and anti-G
      equipment].
AB  - OBJECTIVE: To investigate the +Gz protection of the on board oxygen generating
      system (OBOGS) and anti-G equipment. METHOD: Physical and physiological tests of
      the OBOGS and anti-G equipment were accomplished using human centrifuge. +Gz
      tolerance of ten male subjects with or without the anti-G suit, pressure
      breathing for G (PBG) and OBOGS were determined. RESULT: The performance of the
      OBOGS and anti-G equipment fulfilled the requirements. The +Gz protections of the
      anti-G suit, PBG, and anti-G system were 2.08 G, 1.92 G, and 3.92 G,
      respectively. CONCLUSION: The +Gz protection of the OBOGS and anti-G equipment
      satisfy the performance requirements of high performance aircraft.

PMID- 11965684
TI  - [A study of genetic stability of male sterile mutant of maize obtained from space
      flighted seeds].
AB  - OBJECTIVE: To select a male sterile mutant of maize through space flight for
      production application. METHOD: Air dried seeds of maize (Chuan Dan No. 9) were
      carried to space for 15 d. After returned to the earth, a male sterile mutant was
      selected and a sterile line was obtained through direction breeding. RESULT: It
      was found that the sterile material was thoroughly abortive. The sterile was
      trail stable and expressed a genetic feature of single recessive gene controlled
      nucleus sterility. CONCLUSION: The appearance of male sterile mutant was due to
      gene mutation caused by space conditions.

PMID- 11965685
TI  - Empirical evaluation of a selection system for Chinese student pilots.
AB  - OBJECTIVE: To describe the transfer of ab-initio pilot selection methods from
      Germany to China. METHOD: The different phases of test development and evaluation
      were carried out by the DLR Department of Aviation and Space Psychology in
      cooperation with the Civil Aviation Flying College (CAFC). The DLR/LH test-system
      covers factors of aviation related knowledge, operational abilities, personality,
      and psychomotor abilities. After the translation into Chinese and necessary
      cultural adaptations a sample of 125 Chinese student pilots was examined in 1996.
      Standardized feedback data was gathered over a time period of two years in
      practical flight training. RESULT: In comparison to reliabilities of the German
      version, differences can be observed for all knowledge related test forms.
      Especially tests of technical and mathematical knowledge have somewhat lower
      reliabilities in China. On the other hand the reliabilities for the personality
      questionnaire as well as for the tests of memory, mental concentration, and
      spatial abilities seem to be equivalent with the German versions. In relation to
      flight instructor ratings for all students who passed the selection, the overall
      rate of accurate predictions is 71% (Cramer's V=0.35, P<0.01). The best
      psychometric predictors found in this research for different phases of the
      Chinese ab-initio pilot training (from academic study up to advanced twin-engine
      operation) are psychomotor coordination in multiple tasks settings, mental
      concentration, spatial abilities, and English language comprehension. CONCLUSION:
      The results supported the assumption that the selection tests for ab-initio
      pilots can be transferred into a different culture without significant loss of
      reliability or validity.

PMID- 11965686
TI  - [Pathologic changes induced by sustained acceleration].
AB  - This paper mainly reviewed sustained +Gz acceleration-induced pathologic changes
      in various organ systems. Some of them are reversible and some may result in
      damage. Degree of the pathologic changes are related to G levels, G onset rates,
      duration of G exposure and individual difference factors. With raise of aircraft
      performance, acceleration problem is becoming more and more serious. Aviation
      medical workers should pay good attention to these changes and the use of high
      performance anti-G measures in order to ensure safety and performance of the
      pilots.

PMID- 11965687
TI  - Cancer services. It's all right for some.

PMID- 11965690
TI  - Is a child's health record confidential?

PMID- 11965691
TI  - A year is a long time in nursing.

PMID- 11965692
TI  - Better out than in.

PMID- 11965693
TI  - Long live the generalist nurse.

PMID- 11965694
TI  - Who's afraid of clinical governance?

PMID- 11965695
TI  - Clinical governance in the real world.

PMID- 11965696
TI  - Applying clinical governance in hospice care.

PMID- 11965697
TI  - When parents have a mental illness.

PMID- 11965699
TI  - Paediatric risk assessment in an adult setting.

PMID- 11965700
TI  - Rotational programmes for newly qualified nurses.

PMID- 11965710
TI  - [Tocolysis and its place in premature labor].
AB  - Premature labour ranges from 6 to 8 per cents from all of the deliveries but it
      causes 75 80 per cents of the perinatal infant mortality. The purposes of the
      present research are: to prove the benefit of the tocolytic therapy in case of
      progressing premature labour (cervical dilatation 3 and more cm and
      distinguishable uterine contractions--at least 2 in 10 min for more that 1 hour);
      to compare the efficiency of the medicines used in tocolysis, as well as their
      influence on the maternal and infant morbidity and mortality; A successful
      tocolysis is considered to be the one, which delays the delivery for at least 48
      hours. The authors concluded, that there is not any significant statistic
      difference in the tocolysis success with beta-adrenomymethics and the use aquatic
      solution of Magnesium sulfate. Better results were achieved in the cases when
      Indomethacin was added to the basic tocolytic medicine. No significant harms were
      observed in the maternal and infant organisms in result of the tocolytics
      application. It has been found that after the tocolytic therapy application the
      newborns were with greater birth body weight and the percentage of the
      respiratory distress was lower, compared to the group with expectant behaviour at
      hospitalization.

PMID- 11965711
TI  - [Consciousness during anesthesia for cesarean section].
AB  - 47 women on which sectio cesarean has been done in occasion of belvic-fetal
      disproportion, anatomical abnormalities of the pelvis, bad position of
      presentation. We studies presence of consciousnes spontaneous realtion to pain
      and possibility for contact according the method of Tunstall M.E. It was proved
      that the use of benzodiazepin derivate--Dormicum impacts substantially
      influensences of the studied processes. Introduction anaesthetics (thiopental
      kalipsol, dormicum-kalipsol and thiopental and helothan in 0.3%) are reliable
      protection against the operative stress during sectio cesarean and give adequate
      anaesthesia until baby is born.

PMID- 11965713
TI  - [Primary hormone treatment of early endometrial cancer].
AB  - Six cases of primary treated endometrial cancer are included in this research
      work. Five of these women ended with tumour regression and 2 with pregnancies and
      deliveries of children. All of the women are still alive without having disease
      with mean follow-up period of 36.5 months (from 16 to 80 months). We consider
      that this is very promising method of treatment to offer y conservative treatment
      with high level of survival and possibility for having y child. Diagnostic and
      therapeutic data for the patients who are with early endometrial cancer and wish
      to have y child are analyised in this study. Four of the women were treated with
      GnRh-analogs-Zoladex and 2 with progestins-high doses.

PMID- 11965712
TI  - [Primary carcinoma of the fallopian tube: state of the problem and a case
      report].
AB  - The cancer of the fallopian tube is one of the most rare malignant diseases of
      the female genital tract. The authors present a case of a 66-year old women, that
      was difficult for diagnosis and interpretation of the clinical appearance and the
      results of biopsic curettage. The discussion of the case is accompanied by a
      literature review for the last five years concerning diagnosis, prognosis and
      treatment of this rare disease.

PMID- 11965715
TI  - [Two cases of newborns with persistent pulmonary hypertension syndrome --
      difficulties in diagnosis and treatment].
AB  - The persistent pulmonary hypertension syndrome is a heavy and very often a lethal
      complication in the neonatal period. It is more common in full-term infants with
      perinatal asphyxia, meconium aspiration or inborn infection. We discuss two
      clinical cases of newborns, delivered by Caesarian section in the 38th week of
      gestation without history of prenatal asphyxia or inborn infection. The main
      clinical symptom was a progressive lung failure that finally lead to mechanical
      ventilation. Both infants had clinical symptoms of pulmonary hypertension and
      intracranial hemorrhages (proved by ultrasound). During autopsy, bilateral
      pneumonia and intracranial hemorrhages were found in both infants and in one of
      them meconium aspiration and suprarenal gland hemorrhages were proven. In
      conclusion we may say that the diagnosis of persistent pulmonary hypertension is
      often very difficult and the conventional methods of mechanical ventilation and
      medicament treatment cannot always prevent the infant's lethal outcome.

PMID- 11965714
TI  - [Administration of exogenous surfactant in premature very low birth weight
      infants with RDS].
AB  - A retrospective study is carried out with the aim of establishing the effect from
      surfactant therapy on pulmonary function, survival and complication from
      intensive therapy on VLBWI with RDS. 67 premature infants below 1500 grams are
      included in the study divided in 3 groups: I gr.--27 babies treated with
      Corosurf; II gr.--16 babies treated with Exosurf; III gr.--24 control babies
      without surfactant. The results show that in spite of relatively lower
      gestational age and higher incidence of inborn infection in group I, Curosurf
      treated babies spend shortest time on mechanical ventilation and oxygen therapy
      showing lower incidence of BPD, IVH and mortality rate.

PMID- 11965716
TI  - [Second trimester pregnancy termination with and without prostaglandins].
AB  - The effectiveness of three methods for second trimester pregnancy termination
      [TOP) was compared. A retrospective analysis was made in 34 cases with TOP by
      intraamniotic saline instillation and 19 cases with extra-amniotic appreciation
      of y ballon-catheter, followed by stimulation of uterine contractions by
      intravenous oxytocin infusion. The results were compared with the ones in 13
      prospectively studied cases in which the extra-amniotic appreciation of the
      ballon-catheter was preceded by treatment of the cervix with 0.5 mg prostin E2
      intracervically. In nulliparous patients the treatment of the cervix with y
      single dose prostaglandins did not shorten the mean abortion time neither reduced
      the percentage of unsuccessful and prolonged abortions. In parous patients the
      abortion time was significantly reduced. No failed or prolonged abortions were
      registered.

PMID- 11965717
TI  - [Problems and outcome in very low birth weight infants, with three cases of
      babies under 700 grams].
AB  - Recent advances in neonatal medicine made reality the survival of newborn babies
      of extremely low weight and gestational age. This often provokes ethical problems
      in relation to high death rate, morbidity and neuro-developmental seguels. On the
      other hand it is usually impossible at birth to predict the presence and severity
      of future problems. We present the cases of three babies, where in spite of the
      most unfavourable factors connected to mother's condition, foetus and newborn,
      three healthy children were raised up. Their characteristics at birth are: 650 g-
      30 gestational weeks; 560 g--29 gestational weeks; 600 g--29 gestational weeks.
      In all of them intensive resuscitation and mechanical ventilation are started
      immediately after birth, two of them received prophylactic surfactant. Little by
      little, the problems arising from extremely low birth weight, faded away. All
      babies had grade I-II IVH which were totally resorbed. The first baby is three
      years old at the moment with were totally resorbed. The first baby is three years
      old at the moment with adequate for her age mental and neurologic development.
      The other two babies, resp. 9 and 3 months of age, are also developing normally.
      In conclusion, the possibilities for survival and raising up of babies of
      extremely low weight and gestational age are definitely increasing, requiring
      high qualification staff, modern technics and very large funds for diagnostics,
      monitoring and treatment.

PMID- 11965718
TI  - [A clinical and microbiological study of bacterial vaginosis and vaginitis in
      pregnant women].
AB  - Infectious complications in pregnancy and delivery are still y serious problem in
      obstetrical, gynecological and neonatological practice. The main part of them are
      caused from the anaerobic organisms associated with bacterial vaginosis as well
      from sexually transmitted pathogens. In this study we present data about the
      frequency of spreading of bacterial vaginosis and vaginitis in pregnant women at
      different stages of pregnancy. We held y study of 106 pregnant women aged between
      15 and 35, registrated at the Pregnancy Consultation Office in eleven. About half
      of the women did not have data for genital discharge and the microbiological
      analysis showed normal vaginal flora. Two thirds of the rest investigated women
      had data for candidiasis, bacterial vaginosis, or both. Only one case of
      Trichomonas vaginalis-vaginitis was detected. The results from the microscopic
      examination of the specimens from 10 (9.4%) of the women were suspected for N.
      gonorrhoeae and/or Chlamydia trachomatis-cervicitis. Group B streptococci in
      significant quantity was found in five cases. These results showed high frequency
      of spreading of bacterial vaginosis and cervico-vaginitis in pregnant women.

PMID- 11965719
TI  - [Ultrasonographic hysteroscopy--new approach for the investigation of the uterine
      cavity in women with postmenopausal bleeding].
AB  - PURPOSE: To assess the value of Transvaginal sonohysterography (SHG) in the
      detection of endometrial pathology in patients with postmenopausal uterine
      bleeding, without visualization of the endometrial on the Transvaginal
      ultrasonography (TVS). STUDY DESIGN: Sixty postmenopausal patients with abnormal
      uterine bleeding, without sonographic visualization of the endometrium on the
      Transvaginal ultrasonography underwent sonohysterography, diagnostic hysteroscopy
      and curettage. RESULTS: After comparing the hysteroscopic and sonohysterographic
      results, Sonohysterography showed a sensitivity of 100%, specificity of 94,
      accuracy of 95%, positive predictive value of 85% and negative predictive value
      of 100%. Hysteroscopy showed a sensitivity of 85%, specificity of 100%, accuracy
      of 95%, positive predictive value of 100% and negative predictive value of 94%.
      CONCLUSION: Transvaginal Sonohysterography is an easy, save and the most accurate
      technique for detecting endometrial pathology and endoluminal masses.

PMID- 11965720
TI  - [Forearm density in women with early menopause].
AB  - The early menopause is well known to have deleterious effects on bone mass.
      Trabecular bone is thought to be mainly affected. Aim of this study was to
      produce evidence on charges in forearm total, cortical and trabecular bone
      density in women with early menopause. The study included 40 women menopaused
      before the age of 43 years and 44 age- and size-matched healthy controls,
      menopaused after the age of 45 years. Bone densitometry was carried out on a
      single X-ray DTX-100 densitometer. A special calculation procedure was used to
      determine bone density of cortical and trabecular bone. The early menopaused
      women had low bone density both at the Distal (mainly trabecular) bone. We
      conclude that early-onset menopause affects mainly trabecular bone and causes
      premature ageing of bone.

PMID- 11965721
TI  - [Hysterectomy--a time for reappraisal].
AB  - Hysterectomy is the most common non-pregnancy-related surgical procedure
      performed worlwide. The objective of our study was to investigate the
      hysterectomy by age, indication and surgical method employed during 1994-1998 in
      Department of Obstetrics and gynecology of Higher Medical Institute-Plovdiv,
      Bulgaria. During the period 1352 hysterectomies are performed. The most common
      indication was uterine myoma--50.3%. The most frequently the removal of the
      uterus is made at the age of 45-49. The low percentage of vaginal hysterectomies
      has been noticed--4.6%, as well as the comparatively frequent removal of the
      ovaries along with hysterectomy for benign diseases. A thorough analysis has been
      made in order to reduce the unnecessary hysterectomies, to choose the right
      approach and extend of the operation.

PMID- 11965722
TI  - [Grading intraductal breast carcinoma].
AB  - Mammographic screening has led to increased detection of intraductal carcinoma of
      the breast (IdC). IdC is y heterogeneous disorder with different clinical
      outcomes. The study was designed to confirm consensibility of the three-tiered
      classification, accepted by Thomas Jefferson University Consensus Conference
      since 1997. The study population comprised 30 patients with IdC including
      patients with T1 mic and T1a. Sixty percent of IdC were classified as II-nd
      grade, 27% were III-rd grade and 13% as I-st grade. 20% of IdC exhibited
      heterogenity of grade. The cases with cribriform and papillary architecture were
      1-st or II-nd grades. The other cases with comedo and solid architecture we are
      II-nd or III-rd grades. The cases with invasive component (T1 mic u T1a) were 25%
      -I-st grade, 75%--II-nd grade and III-rd grade--87.5%. In conclusion, the grading
      of IdC could y prognostic factor in far long term prognosis of patients with
      those lesions.

PMID- 11965723
TI  - [Pain relief during labor].

PMID- 11965724
TI  - [Frequency of anti-sperm antibodies demonstrated by classical tests for sperm
      antibodies in patients with unexplained infertility].
AB  - The aim of the present investigation was to establish the frequency of sperm
      antibodies in patients with etiologically unexplained infertility, and to compare
      the demonstrated frequencies with the results from y control group of y healthy
      blood donors, as well as with the results of other investigators. The gelatin
      agglutination test of Kibrick and the tray agglutination test of Friberg were
      applied to test 244 sera from infertile patients and 50 sera from healthy blood
      donors at the Laboratory of Immunology of Reproduction, Department of Biology,
      Medical University of Sofia. For the infertile patients, relevant sperm antibody
      titers were demonstrated in 2.5% (titer > or = 16) for the Kibrick method, and in
      7% (titer > or = 32) for the Fiberg method. The test of Kibrick did not reveal
      significant antibody titers in the healthy controls, while the test of Friberg
      showed sperm antibodies in 2% of the blood donors. Fisher's exact test
      demonstrated extremely significant correlation (p < 0.0001) between the presence
      of sperm antibodies in sers of patients with unexplained infertility as revealed
      by the tests of Kibrick and Friberg. Most often mixed agglutinates were
      demonstrated in the Friberg test. In contrast with the results of other
      investigators head-to-head agglutinins were observed more often in male sera,
      while tail-to-tail agglutinins--in female sera. Finally, the results from the
      present investigation, as well as the analyzed literature data showed a low
      frequency of anti-sperm immunity in the Bulgarian population. The established
      high degree of correlation between the tests of Kibrick and Friberg, the good
      reproducibility of the results and the low cost of these methods confirm their
      appropriate use for the diagnosis of sperm antibodies in patients with
      unexplained infertility.

PMID- 11965725
TI  - [Risk factors for the development of ovarian carcinoma].

PMID- 11965726
TI  - [Problems of diagnosis and treatment of cervicitis].
AB  - Infectious cervicitis is a common disease in women of reproductive age. The
      symptoms are not characteristic and they are often neglected by the patient and
      the physician. Cervicitis is a very important clinical entity, because the
      infection can ascend to the genital tract. The most common causes for the
      infectious cervicitis are Chlamydia trachomatic and Neisseria gonorrhoeae. A
      variety of methods for the precise diagnosis must be employed--gynecologic
      examination, colposcopy, pathomorphology and cytology and bacteriological
      examination as well. Therapeutic modalities must include coverage for both
      Chlamydia trachomatis and Neisseria gonorrhoeae. Bacteriological test of cure is
      mandatory.

PMID- 11965727
TI  - [Prenatal ultrasonographic diagnosis of four cases of sacrococcygeal teratoma].
AB  - Four cases of SCT, diagnosed antenatally by the authors are reported. The reasons
      for referal to the department, the sonographic findings, the obstetric
      management, the outcome for the fetus and the histologic findings are summarized
      for each particular case. In the first case y 23 years old primigravida was
      admitted to the Hospital because of hydramnious and threatened premature labour
      in 30 w.g. The ultrasound examination revealed an AGA fetus with y tumor mass
      with y mixed structure protruding from the sacrococcygeal region. Despite the
      tocolytic therapy two days after admission to the department y 2400 grams
      severely asphyxiated fetus was born. Neonatal death occurred 15 minutes after
      delivery. In the second case y 28 years old primigravida was referred to the
      hospital because of acute hydramnios in 31 w.g. The ultrasound examination
      revealed an AGA fetus with y predominately solid mass with calcifications,
      110/120 mm in dimentions in the sacrococcygeal region. Despite the indomethacin
      therapy on day 4th of admission spontaneous labour started. During a vaginal
      examination avulsion of the presenting "mass" occurred followed by rapid
      exsanguination of the fetus. In the third case the anomaly was diagnosed in the
      second trimester and genetic counseling of the couple was offered. The karyotype
      of the fetus was normal but the parents chose termination of pregnancy despite
      the advanced gestational age (29 w.g. by that time). A 1900 gramas live female
      infant was born and was emergently referred to the Neonatal Surgery Department
      and operated on 4th day after delivery. Unfortunately the baby died 24 hours
      after the operation from an accident, not related to the operation. In conclusion
      y protocol for obsteric management of pregnancies with SCTs of the fetus is
      proposed by the authors.

PMID- 11965728
TI  - [Use of the balloon catheter before induction of labor with oxytocin in cases
      with unfavorable pelvic score and premature delivery].
AB  - The purpose of this prospective work is to communicate the experience with
      preinduction treatment with Folly's catheter on the Pelvic score (Ps), labor and
      neonatal outcome in 52 cases in 27 to 34 wg, preterm premature labor and
      unfavourable cervix. The first control group consist of 24 pregnancies with the
      same characteristics but with favourable cervix at the begging of labor induction
      and the second control group include 31 cases with spontaneous premature labor.
      The Folly's catheter is introduced through the cervical canal and the bulb
      inflated with 75 ml of sterile normal saline. After the Foley's catheter dropped
      out the Ps is reassessed and proceed with oxytocin infusion. In the first control
      group with favourable cervix the induction of labor is only with oxytocin via
      infusion pump. More than half of all patients are treated with with tocolysis.
      The results show that for the period of tocolysis and/or PPROM there is
      significant improvement of the Ps (from 0.90 +/- 0.9 to 2.35 +/- 1.5). The change
      in the Ps doesn't depend on the g.w., the length of tocolysis or on the initial
      Ps. The balloon catheter improve the Ps from 2.35 +/- 1.5 to 6.24 +/- 1.3 for y
      period of 3 h 20 min (2 h 40 min to 4 h, 95% confidence). After the Foley
      catheter dropped out the duration of labor with oxytocin infusion is 6 h (5 to 7
      h, 95% confidence) and is not different from this in the control groups. The time
      for the catheter to drop out, the achieved Ps and especially the effacement of
      the cervix are essential features in the prognosis of the difficulties in the
      labor process and the neonate state.

PMID- 11965729
TI  - [Current treatment during life-threatening hemorrhages in obstetrics].
AB  - For the death of one third of the women in childbirth, the cause is a rich
      blooding after normal or surgical birthpermission. Blood loosing is especially
      dangerous when its quantity is more than 1000 ml. Typically for the clinical test
      is the expressed tahicardia and the sharply going down of the blood pressure. The
      facts, leading to this hard complicating are more than ten, as one of them is the
      surgical birth. There are cited authors, who define the contemporary treatment in
      this hard complicating. The tendency is to save the uterus, especially for young
      women and for these who have not alive children. For that purpore is used the
      linking of arterial blood vessels providing blood to the uterus and its lineal
      ways. It's described the treatment in these cases in state university hospital
      "Maichin dom". The author definitely concider that it is a high time that methods
      to find more application in the contemporary obstetrics in our country.

PMID- 11965730
TI  - [A case of invasive cervical carcinoma associated with pregnancy].
AB  - The cervical cancer is the most usual neoplastic disease, which takes place
      during the pregnancy. The prognosis for the women depends mostly of the clinical
      stage and the presence of nodal metastasis. The principes of the treatment do not
      differ from the standard oncologic therapy in nonpregnant women. Differencies
      exist in the way and the time of the terminanation of the pregnancy. The authors
      present y case of pregnancy and invasive cervical adenocarcinoma diagnosticated
      in m. 1.X. immeadiately after cesarean section an extended hysterectomy y modo
      Piver 111 with pelvic nodal dissection is done.

PMID- 11965731
TI  - [Tocolytic treatment of pregnant women with threatened abortions and preterm
      labor in the second and third trimesters of pregnancy with magne B6 (a
      preliminary communication)].
AB  - The authors check the effect of the substitutional treatment of the pregnant
      patients with the uterine paints and contractions in the second and third months
      periods of the pregnancy with "Magne B6"--Sanofi. In the group of the examined
      patients the Mg deficiency that is the cause for these suffering has been
      established. After the substitutional treatment with "Magne B6" the described
      suffering disappeared and clinical-lab values of Mg in the serum and urine
      normalized.

PMID- 11965732
TI  - [Current treatment of bacterial vaginosis].
AB  - Therapeutic options for the treatment of accurately diagnosed bacterial vaginosis
      are reviewed on the basis of current concepts for treatment of bacterial
      vaginosis. The importance for screening for bacterial vaginosis is pointed out
      especially before intrauterine procedures and in pregnant women at risk for
      premature deliveries. Treatment regimens for pregnant women are discussed as
      well. Emphasis is given to treatment modalities for recurrent bacterial
      vaginosis.

PMID- 11965733
TI  - [Current state and prospects of development of railway hygiene].
AB  - Current planning in railway hygiene is conducted according to the special
      requirements of railway industry. Specific medical and prophylactic programs
      specified are on safety arrangements of railway workers, environmental protection
      in connection with intensive functioning of railways. The authors represent major
      prospective trends of research in occupational medicine and industrial ecology
      for railway transport.

PMID- 11965734
TI  - [Bases for allowable norms of infrared radiation exposure in accordance with the
      radiation spectrum].
AB  - Specification of norms is the most radical protective means in a system of
      activities reducing harmful influence on human health. For effective work of
      norms, the authors specified hygienic classification covering industrial sources
      of infrared radiation. The classification is based on biologic effect
      peculiarities depending on maximal energy in the radiation spectrum. Requirements
      to measuring devices and measurement procedures were specified as well. Nowdays
      production of sensitive devices measuring the spectrum energy is launched in
      Ukraine, so it is time to put the novelties into practice.

PMID- 11965735
TI  - [Comparative evaluation of methods accepted by Russian and international
      standards to assess total resistance of special cold-proof clothing set].
AB  - Experimental studies helped to compare methods determining and calculating total
      heat resistance of clothing sets accepted by Russian and international standards.
      Findings are that difference in the total heat resistance values calculated on
      humans and on dummies in relatively still air and quiet conditions is caused by
      measurement technique applied. Significant difference in the total heat
      resistance values calculated in windy conditions or during walk require further
      research aimed to study influence of those factors on clothes' heat resistance.

PMID- 11965736
TI  - [Safety problems of occupational activity during alcoholic intoxication].
AB  - It has been established that work efficiency of persons occupied by machine
      operating duties degrades markedly under the action of an acute alcoholic
      intoxication--less on real machines and more on simulators and when operating
      simple technical devices. Work efficiency degradation is manifested by the task
      execution time increase (to a lesser degree) and by erroneous action quantity
      increase after taking alcohol, i.e. by work reliability decease. Most heavily it
      is manifested during the first 0.7-1.5 hr. After taking alcohol. And direct work
      efficiency index is usually improved 12-16 hr. after taking alcohol. Increase of
      erroneous action quantity is caused probably by a series of physiological,
      psychophysiological and psychological changes in the condition of a man under the
      action of alcohol. Time of the day when the activity takes place after taking
      that dose of alcohol is practically non valid for changing work efficiency index.

PMID- 11965737
TI  - [Effects of vibration on the immune system (analytical review)].

PMID- 11965738
TI  - [Tactics of protection of humans in accidents associated with combined exposure
      to chemical and physical factors].

PMID- 11965739
TI  - [Examination of drug therapy quality in obligatory medical insurance system].

PMID- 11965741
TI  - [Medical and technical problems of water transport hygiene].
AB  - Analysis of causes for sea accidents proves importance of human factor in a
      system "human--environment--transport". The authors consider possibility that
      such physical factors as noise, vibration, direct and alternate magnetic fields
      harm sailing staff's functional state. A universal water transport system of
      hygienic control over physical factors on ships is considered expedient.

PMID- 11965740
TI  - [Hygienic aspects of exposure to polyfluorinated sulfur compounds when used as
      inert media].

PMID- 11965742
TI  - [Role of nonspecific cellular resistance factors in hygienic evaluation of
      electromagnetic nonionizing radiation].
AB  - The most sensitive indices of the blood system at EMF exposure (disorders of
      megakaryocytes differentiation, unspecific reactions, repopulation of the blasts
      cells a. al.) have been determined by the cytologic investigations. At has been
      revealed that allowable UVF levels effect are situated below the threshold of
      activisation of adaptive reactions (less than 0.01 mV/cm2), for occupational
      conditions--at the level of compensatory processes (0.05-0.1 mV/cm2). The
      intensities higher than 0.5 mV/cm2 were estimated as critical. Involution of
      megakaryocytes, polimorphism and disturbances the structure of leucocytes a. al.
      were revealed as EMF markers which allow to carry out an express-diagnostic.

PMID- 11965743
TI  - Blair's top-up cash pledge given a mixed reception.

PMID- 11965744
TI  - Whistleblowing. Seen but not heard.

PMID- 11965746
TI  - Recruitment. Young, bright, on the way up.

PMID- 11965745
TI  - Hospital nutrition. Celebrity gimmicks won't feed patients.

PMID- 11965747
TI  - Mental health. Grim wards an acute problem.

PMID- 11965748
TI  - Cancer care. Painful ignorance.

PMID- 11965749
TI  - Do you have to be a nurse in order to be a health visitor?

PMID- 11965750
TI  - A prescription for change.

PMID- 11965752
TI  - Racism: is there a case for positive discrimination?

PMID- 11965753
TI  - Insults won't stop us telling kids about sex..

PMID- 11965754
TI  - A herb for migraine.

PMID- 11965755
TI  - Racism: is there a case for positive discrimination?

PMID- 11965756
TI  - Racism: is there a case for positive discrimination?

PMID- 11965757
TI  - NVQs from the horse's mouth.

PMID- 11965758
TI  - Care for the carers.

PMID- 11965759
TI  - Masters of all trades.

PMID- 11965760
TI  - Let's see red on December 1.

PMID- 11965761
TI  - Nipping scandals in the bud.

PMID- 11965762
TI  - Coming clean.

PMID- 11965763
TI  - Why are older people left out?

PMID- 11965764
TI  - Stretched to the limit.

PMID- 11965765
TI  - There's a long way to go before nurses blow the whistle with impunity.

PMID- 11965766
TI  - Breast cancer: an overview.

PMID- 11965767
TI  - Vaccine therapy and cancer.

PMID- 11965768
TI  - Shaping the future of shared governance.

PMID- 11965769
TI  - Capital's nurses 'conned' over pay.

PMID- 11965770
TI  - Staff 'poached' from abroad.

PMID- 11965771
TI  - Public health specialists in action.

PMID- 11965772
TI  - Compression bandaging--3.

PMID- 11965773
TI  - Security chief calls for NHS police force.

PMID- 11965775
TI  - Making a point of safety.

PMID- 11965774
TI  - Child abuse swamps HVs.

PMID- 11965776
TI  - NICE to vet anti-smoking treatments.

PMID- 11965777
TI  - Multidrug-resistant tuberculosis. Trusts fail to combat TB risk.

PMID- 11965778
TI  - HV training cut by 40%.

PMID- 11965779
TI  - Accused 'needlessly' struck off by UKCC.

PMID- 11965780
TI  - Nurse chief under fire.

PMID- 11965781
TI  - Named and shamed: the shape of things to come.

PMID- 11965782
TI  - Human rights. Act expands advocacy role.

PMID- 11965783
TI  - Crime. Beatle attacker 'failed by NHS', says his mother.

PMID- 11965784
TI  - Smoking. '35 years and I've kicked it'.

PMID- 11965785
TI  - Paediatric nursing. A brush with meningitis that showed NHS at its best.

PMID- 11965786
TI  - Review of the year 2000.

PMID- 11965787
TI  - Telephone triage. Jury still out on safety of NHS direct.

PMID- 11965788
TI  - Alder Hey. Your child may need a fourth funeral.

PMID- 11965789
TI  - No smoking campaign. 'I ran up the stairs!'.

PMID- 11965790
TI  - Should nurses feed patients themselves?

PMID- 11965791
TI  - Be the grit in the oyster of nursing.

PMID- 11965792
TI  - Heads you lose.

PMID- 11965793
TI  - Nurse prescribing needs high standards.

PMID- 11965794
TI  - Are nurses colour blind?

PMID- 11965795
TI  - Theory is not enough.

PMID- 11965797
TI  - When your parts drop off, look for a happy fitter.

PMID- 11965796
TI  - Older people are neglected.

PMID- 11965798
TI  - Let's make better porridge.

PMID- 11965799
TI  - Tickling patients' taste buds.

PMID- 11965800
TI  - Happy eaters.

PMID- 11965801
TI  - Anyone for a coffee enema?

PMID- 11965802
TI  - The only way to bump up nurse numbers is to bump up the numbers on their pay
      slips.

PMID- 11965803
TI  - Can nurses improve patient feeding?

PMID- 11965804
TI  - Shingles: diagnosis and treatment.

PMID- 11965805
TI  - Symptom control for breast cancer.

PMID- 11965806
TI  - Recruitment. RCN declares war on Blair's nurse numbers.

PMID- 11965807
TI  - New conceptions on issues of fertility.

PMID- 11965808
TI  - A fair hearing.

PMID- 11965809
TI  - Measuring apex and radial pulse.

PMID- 11965810
TI  - Learning curve.

PMID- 11965811
TI  - Pay award. Bumper Xmas predicted.

PMID- 11965812
TI  - NHS mergers. Scots plan to ditch trusts.

PMID- 11965813
TI  - Winter crisis. Mild weather militates against flu outbreak.

PMID- 11965815
TI  - Ireland scraps course fees for nurse returners.

PMID- 11965814
TI  - Blunders led to diabetes death.

PMID- 11965816
TI  - Nurses 'prefer flu to understaffed wards'.

PMID- 11965817
TI  - Family-friendly policies. Students to get maternity pay.

PMID- 11965818
TI  - Time to make a plea for the non-believers.

PMID- 11965820
TI  - Queen's speech. Boost for prescribing.

PMID- 11965819
TI  - Nurse prescribing. UKCC backs radical plan.

PMID- 11965821
TI  - Health effects of physical activity.
AB  - OBJECTIVES: This article examines the potential protective effect of leisure-time
      physical activity on the incidence of heart disease and depression. DATA SOURCE:
      The data are from the household longitudinal component of the 1994/95 and 1996/97
      cycles of the National Population Health Survey, conducted by Statistics Canada.
      Results are based on two subsamples: 7,158 respondents aged 20 or older who were
      healthy and free of heart disease in 1994/95, and 7,593 respondents aged 12 or
      older who were healthy and free of depression in 1994/95. ANALYTICAL TECHNIQUES:
      Multiple logistic regression was used to estimate the effects of leisure-time
      physical activity on the incidence of heart disease and depression, while
      controlling for selected characteristics. MAIN RESULTS: Individuals who were
      healthy and free of heart disease or depression in 1994/95 and who engaged in
      regular physical activity at a moderate level of energy expenditure had lower
      odds of reporting a diagnosis of heart disease or an episode of depression in
      1996/97 than those who were less active.

PMID- 11965822
TI  - Body mass index and health.
AB  - OBJECTIVES: This article describes the prevalence of the four international body
      mass index (BMI) categories--underweight (18.5 or less), acceptable weight (18.6
      to 24.9), overweight (25 to 29.9) and obese (30 or more)--by selected socio
      demographic and lifestyle characteristics. It also examines the association
      between BMI and selected health problems. DATA SOURCE: The data are from the
      household component of the 1996/97 National Population Health Survey, conducted
      by Statistics Canada. Results are based on a sample of 50,347 respondents aged 20
      to 64. ANALYTICAL TECHNIQUES: Prevalence estimates of BMI categories were
      calculated. Multivariate analyses were used to examine associations between BMI
      and various health conditions by smoking status, while controlling for age and
      sex. MAIN RESULTS: In 1996/97, about half of Canadian adults were in the
      acceptable weight range; 34% were overweight; 12%, obese; and 2%, underweight.
      Being overweight or obese was associated with asthma, arthritis, back problems,
      high blood pressure, diabetes and thyroid disorders, although this varied with
      smoking status. Underweight smokers had high odds of reporting cancer, bowel
      disorders, ulcers, and migraine.

PMID- 11965823
TI  - Medications and fall-related fractures in the elderly.
AB  - OBJECTIVES: This article examines associations between the use of selected
      medications and fall-related fractures in the household population aged 65 or
      older. DATA SOURCE: The analysis was based on cross-sectional data from the
      household component of the 1996/97 cycle of the National Population Health
      Survey. Data were from a sample of 13,363 respondents aged 65 or older.
      ANALYTICAL TECHNIQUES: Descriptive statistics and multivariate analyses were used
      to study cross-sectional associations between selected medications used in the
      previous month and fractures occurring in the previous year. Multiple logistic
      regression analyses controlled for potentially confounding factors. MAIN RESULTS:
      Among elderly individuals who sustained any activity-limiting injury in 1996/97,
      an estimated 65,000 reported the most serious such injury had been a fall-related
      fracture. The odds of a fall-related fracture were significantly low among people
      who were taking diuretics/antihypertensives. Arthritis and urinary incontinence
      were positively associated with fall-related fractures.

PMID- 11965824
TI  - Dental insurance and use of dental services.
AB  - OBJECTIVES: This article examines socioeconomic differences in insurance for
      dental services among Canadians aged 15 or older and factors associated with the
      use of dental services. DATA SOURCE: The data on dental insurance coverage and
      use of dental services are from the cross-sectional file of Statistics Canada's
      1996/97 National Population Health Survey. The sample size of respondents aged 15
      or older was 70,884. ANALYTICAL TECHNIQUES: Logistic regression analysis was used
      to model variables related to dental insurance coverage and to dental visits in
      the past year. A weighted bootstrap resampling procedure was used to derive
      variance estimates. MAIN RESULTS: In 1996/97, 53% of the population aged 15 or
      older reported having dental insurance, and 59% said they had visited a dentist
      in the past year. But even when they had insurance, individuals with low incomes
      and low educational attainment had much lower odds of visiting a dentist than
      those with higher incomes and more education.

PMID- 11965825
TI  - Mortality in metropolitan areas.
AB  - OBJECTIVES: This article examines differences in all causes mortality rates and
      rates for the leading causes of death (heart disease, cancer and cerebrovascular
      disease) by census metropolitan area (CMA). DATA SOURCE: The data are from the
      Canadian Vital Statistics Data Base maintained by Statistics Canada. ANALYTICAL
      TECHNIQUES: Annualized age-standardized mortality rates were calculated for
      Canada and for each CMA for the three-year period from 1994 to 1996. Differences
      between the CMA rates and the national rate were examined. MAIN RESULTS:
      Mortality rates tend to be high in CMAs in the Atlantic provinces and Quebec and
      low in CMAs in the Prairies and British Columbia. Ontario contains CMAs with some
      of the highest mortality rates in Canada, as well as others whose rates are among
      the lowest. The pattern of mortality for specific causes also differs within
      CMAs: a CMA may have a high death rate for one cause, but a low rate for another.

PMID- 11965827
TI  - The economic burden of insulin resistance.
AB  - Diabetes mellitus has reached epidemic proportions worldwide as we enter the new
      millennium. The World Health Organization (WHO) has commented there is 'an
      apparent epidemic of diabetes which is strongly related to lifestyle and economic
      change'. Over the next decade the projected number will exceed 200 million,
      possibly reaching 250 million persons. Most will have type 2 diabetes and all are
      at risk of the development of complications. Better education, improved
      nutrition, more exercise, early diagnosis and prompt treatment are imperative.
      Diabetes is a serious disease, subject to the development of many complications
      affecting large vessels (heart, cerebral and peripheral), small vessels (kidney
      and retina), nerves and other organs. In type 2 diabetes these complications may
      precede diagnosis of the disease by many years. The process continues inexorably,
      with premature mortality and morbidity mainly from the development of vascular
      disease. Data from the WHO confirm the principal role of non-communicable disease
      on mortality in developed countries, while mortality in developing countries is
      rising rapidly, now often exceeding communicable disease. The non-communicable
      diseases are divided into cancer and degenerative diseases. In the developed
      world, degenerative diseases are grouped to include ischaemic heart disease,
      stroke, renal failure, hypertension and other macro- and microvascular diseases.
      The major complications of diabetes encountered most frequently and with the
      greatest impact are: 1. Neuropathy, both peripheral and autonomic, with principal
      manifestations in the lower limbs 2. Microvascular disease, mainly affecting the
      retina and kidney, resulting in blindness and renal failure 3. Macrovascular
      disease, presenting with atherosclerosis in the coronary arteries causing
      ischaemic heart disease, cerebrovascular disease causing stroke and peripheral
      vascular disease contributing to diabetic gangrene.

PMID- 11965826
TI  - Dyslipidaemia and coagulation defects of insulin resistance.
AB  - Among the traditional risk factors, dyslipidaemia and coagulation disorders play
      an important role in increasing the risk of coronary heart disease (CHD) in
      patients with type 2 diabetes. The lipid abnormalities of patients with insulin
      resistance and type 2 diabetes include increased triglycerides, lower high
      density lipoprotein (HDL)-cholesterol and the predominance of small dense low
      density lipoprotein (LDL)-particles. The composition of HDL particles is
      different from healthy controls and the concentration of the larger, more anti
      atherogenic particles is decreased in patients with insulin resistance and type 2
      diabetes. Subgroup analyses of several large studies have shown that lowering LDL
      cholesterol with statin treatment decreased cardiovascular events in patients
      with type 2 diabetes. In other studies, gemfibrozil decreased cardiovascular
      events in a subgroup of patients with diabetes, although the decreases were not
      always statistically significant. Platelets from patients with diabetes are more
      sensitive to several aggregating agents, have increased numbers of glycoprotein
      receptors and a lower activity of guanylate cyclase. These factors may contribute
      to the documented hyperreactivity of platelets in patients with type 2 diabetes.
      Other factors in patients with type 2 diabetes include alterations in serum
      fibrinogen, PAI-1, tissue-type plasminogen activator (tPa) and factors V, II and
      VII, which have all been linked to the risk of myocardial infarction. Increased D
      dimer, von Willebrand factor (vWf) antigen, A-II anti-plasmin and decreased anti
      thrombin III were also reported in patients with type 2 diabetes. This pro
      thrombotic risk profile of the circulating blood in type 2 diabetes patients,
      together with the lipid abnormalities, contributes to the increased risk of
      vascular events in this population.

PMID- 11965828
TI  - Thiazolidinedione hepatotoxicity: a class effect?
AB  - Type 2 diabetes mellitus, which affects approximately 7% of the population, is a
      disease of relative insulin insufficiency manifested by insulin resistance in
      skeletal muscle, liver and adipose tissue. This results in increased hepatic
      glucose production with compensatory hyperinsulinaemia. The secondary
      hyperinsulinaemia is associated with an increased incidence of hepatocellular
      carcinoma and non-alcoholic steatohepatitis (NASH). It is estimated that insulin
      resistance is present in 50-70% of patients with NASH and that the incidence of
      NASH in type 2 diabetes is 60-80%. The prevalence of cirrhosis in established
      type 2 diabetes is as high as 10% and the prevalence of hepatitis C is 3-11%. It
      was in this setting that the insulin sensitisers were developed. The
      thiazolidinediones represent a significant and unique pharmacological
      breakthrough for the management of type 2 diabetes mellitus. The first of the
      drugs, troglitazone, proved to be hepatotoxic and has been withdrawn from the
      market. Two cases of hepatotoxicity of rosiglitazone have been reported. It
      remains unclear whether or not hepatotoxicity is a class effect or is related to
      the unique tocopherol side chain of troglitazone. However, it appears that the
      incidence of hepatotoxicity of rosiglitazone is much lower than that of
      troglitazone. It is not yet known if any hepatotoxicity occurs with pioglitazone.

PMID- 11965829
TI  - Pathogenesis of type 2 diabetes: the relative contribution of insulin resistance
      and impaired insulin secretion.
AB  - Type 2 diabetes is characterised by both impaired insulin secretion and insulin
      resistance but their relative contribution to the development of hyperglycaemia
      may differ due to heterogeneity of the disease. Under most circumstances, insulin
      resistance is the earliest detectable defect in pre-diabetic individuals but it
      is not known whether this is the primary defect or secondary to other
      abnormalities such as abdominal obesity with excessive free fatty acid turnover
      and increased lipid deposits in muscle. Initially, enhanced insulin secretion can
      compensate for the insulin resistance but early phase insulin secretion is
      impaired. In the transition from normal to impaired and diabetic glucose
      tolerance, insulin sensitivity deteriorates about 40% whereas insulin secretion
      deteriorates 3-4 fold. In addition to insulin resistance, the metabolic syndrome
      includes hypertension, dyslipidaemia, obesity and microalbuminuria. In patients
      with manifest diabetes, chronic hyperglycaemia can result in further
      deterioration of insulin sensitivity and secretion (glucotoxicity), which is
      aggravated by elevated free fatty acids (lipotoxicity). Abdominal obesity and
      insulin resistance are strongly correlated and studies have aimed at
      understanding the genetic basis. Candidate genes for the metabolic syndrome
      include those for the beta 3-adrenergic receptor, lipoprotein lipase, hormone
      sensitive lipase, peroxisome proliferator-activated receptor-gamma, insulin
      receptor substrate-1 and glycogen synthase. Therefore, type 2 diabetes is
      multigenic and appears to represent a collision between thrifty genes and an
      affluent society. Successful management will require treatments targeted at
      defects of both insulin secretion and insulin resistance.

PMID- 11965830
TI  - Prevention of type 2 diabetes.
AB  - The importance of type 2 diabetes is due to its high prevalence, the difficulties
      in achieving optimal glucose control (financial, time, quality of life) and the
      high frequency of chronic microvascular and macrovascular complications that add
      very significantly to the morbidity, mortality and overall cost of the disease.
      Numerous risk factors have been identified that predict the future onset of type
      2 diabetes in individuals and an early stage of the disease (impaired glucose
      tolerance) can often be identified. Insulin resistance is central to the
      pathogenesis and is initially compensated by an increased insulin secretion. Over
      time, insulin secretion progressively fails and diabetes appears. Several
      approaches have been proposed for the prevention of diabetes. Lifestyle changes
      (nutritional therapy and physical activity) have been shown to reduce the
      frequency of diabetes in small studies and are being assessed in the NIH-funded
      Diabetes Prevention Trial. Metformin, which reduces insulin resistance and
      hyperinsulinaemia, is being assessed in this same trial. Acarbose, which has been
      shown to reduce post-prandial insulin secretion and improve insulin resistance,
      is being assessed in the STOP-NIDDM trial. The ACE inhibitor ramipril has been
      shown in the HOPE study to reduce the appearance of diabetes by one third when
      given to patients with vascular disorders and this class of agents has been shown
      to improve insulin resistance. Another very promising approach is the use of
      thiazolidinediones (rosiglitazone, pioglitazone) to improve the insulin
      resistance and possibly preserve the beta cells by reducing the need for
      increased insulin secretion. These lifestyle changes and medications have been
      shown to be safe in the treatment of type 2 diabetes. There is a high probability
      that one of these approaches will be effective in delaying or preventing type 2
      diabetes, and prevention may become a clinical reality in the near future.

PMID- 11965831
TI  - Prevention of coronary heart disease in type 2 diabetes.
AB  - Patients with diabetes without a prior myocardial infarction are at a similar
      risk of coronary heart disease (CHD) events as non-diabetic subjects with a prior
      myocardial infarction. Furthermore, prognosis after the first myocardial
      infarction is worse in diabetic compared to non-diabetic patients. Therefore,
      management of cardiovascular risk factors in subjects with diabetes should be as
      vigorous as in patients with known CHD who have had a myocardial infarction.
      Randomised controlled trials have shown that efficacy of cholesterol lowering and
      antihypertensive therapy in type 2 diabetes is at least as effective as in non
      diabetic subjects in preventing macrovascular disease. Antiplatelet therapy with
      aspirin reduces the risk of CHD events in high-risk patients and the benefit is
      similar in subjects with and without diabetes. Improved glycaemic control has a
      modest beneficial effect on CHD risk. There is residual excess risk of CHD in
      type 2 diabetes, which is not explained by traditional cardiovascular risk
      factors. Insulin resistance may partly mediate this. Prediabetic subjects who are
      insulin resistant have more adverse levels of triglycerides, high density
      lipoprotein (HDL)-cholesterol and blood pressure than those who are insulin
      sensitive. Moreover, factors associated with insulin resistance are significant
      predictors of CHD events in subjects with diabetes, in addition to conventional
      risk factors. The thiazolidinedione, pioglitazone, improves glycaemia and insulin
      sensitivity in hyperglycaemic patients. It also improves insulin and triglyceride
      levels and lowers blood pressure. Thiazolidinediones have been found to have
      vasculo-protective effects in both acute and chronic vascular injury in animal
      models. For prevention of CHD in type 2 diabetes a multi-factorial approach
      should be considered, including improved glycaemic control, aggressive management
      of dyslipidaemia and hypertension, anti-platelet therapy, reduction of insulin
      resistance and use of agents that improve insulin sensitivity.

PMID- 11965832
TI  - Health outcomes in type 2 diabetes.
AB  - Outcome evaluation is of great interest throughout the healthcare field, but
      which outcomes are important depends on the viewpoint one holds. For the
      healthcare organisation costs and resource utilisation are paramount, whereas
      patients may be interested in being able to work and lead a productive life
      without long-term complications. Healthcare policy decisions are influenced by
      varying degrees of social forces, existing regulations and outcome research
      findings. Ideally, all three are in agreement but often they may be competitive
      or may not even be included in policy decision making. With respect to improving
      outcomes, much energy has been spent on developing diabetes care guidelines.
      However, these have had minimal impact on physician behaviour. Soon after onset
      or diagnosis of diabetes, we are most concerned with process measures such as
      micro-albumin levels, blood pressure monitoring, routine eye and foot
      examinations and lipid profiles. These process measures are related to the
      development of intermediate outcomes--proteinuria, retinopathy, foot ulcers and
      dyslipidaemia. Diabetes is an expensive disease but there is accumulating
      evidence that improved care can lead to better quality of life and reduction in
      health care resource utilisation. The UKPDS demonstrated that for one percentage
      point decrease in HbA1c there was a 35% reduction in the risk of complications.
      Preliminary data from various diabetes management programmes indicate that
      instituting standardised care may lead to cost savings and improved health.
      Rationing health care resources wisely requires consideration of multiple factors
      including quality of life years (QALYs) and healthy year equivalents (HYEs).
      Formal quantitative methods are used to measure overall desirability of a medical
      intervention. Questions to be answered include predictability of responsiveness
      or adverse events to drug therapy. Outcomes research will have a key role in
      future development of models of diabetes care.

PMID- 11965833
TI  - Current treatment of insulin resistance in type 2 diabetes mellitus.
AB  - The two major metabolic perturbations resulting in hyperglycaemia in type 2
      diabetes are insulin resistance and insulin deficiency. Insulin resistance occurs
      in peripheral organs (muscle and fat), leading to decreased glucose uptake and
      utilisation, and in liver, leading to increased hepatic glucose production.
      Thiazolidinediones, pharmacological ligands for PPAR gamma, can modulate the
      expression of genes influencing carbohydrate and lipid metabolism. Pioglitazone,
      a recently introduced thiazolidinedione, improves glycaemic control and lipid
      profiles in people with type 2 diabetes. Some of the possible mechanisms of
      improving glycaemic control include (a) increase in GLUT-1 and GLUT-4, (b)
      enhancement of insulin signalling, (c) decrease in tumour necrosis factor-alpha
      action, (d) reduction in plasma free fatty acid and (e) decrease in PEPCK.
      Together these can increase glucose uptake and utilisation in the peripheral
      organs and decrease gluconeogenesis in the liver. Possible mechanisms resulting
      in more desirable lipid profiles include an increase in phosphodiesterase-3B
      resulting in reduced intra-cellular lipolysis in adipocytes and an increase in
      lipoprotein lipase resulting in enhanced clearance of triglyceride-rich
      lipoproteins(TRLs). Pioglitazone, used as monotherapy or in combination with
      sulphonylurea, biguanide or insulin, improves glycaemic control, lowers serum
      triglycerides and raises high density lipoprotein (HDL)-cholesterol. It enhances
      hepatic and peripheral insulin sensitivity. In clinical trials, there has been no
      evidence of hepatotoxicity or increased incidence of elevated serum ALT in
      subjects taking pioglitazone compared with placebo.

PMID- 11965834
TI  - Medical photography.

PMID- 11965836
TI  - Parkinsonism associated with interferon alpha therapy for chronic myelogenous
      leukemia.
AB  - A 79 year-old man was treated with Interferon alpha for chronic myelogenous
      leukemia and developed severe parkinsonism that resolved after Interferon alpha
      was stopped. Carbidopa-levodopa was associated with early improvement, but
      discontinuation did not result in worsening of the parkinsonism.

PMID- 11965835
TI  - Hyponatremia associated with sertraline and fluoxetine: a case report.
AB  - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a rare
      but serious adverse effect of the selective serotonin reuptake inhibitors
      (SSRIs). Although many case reports describe this association, few report the
      effect of rechallenge with another SSRI. We present a case of an elderly patient
      who developed hyponatremia with sertraline and SIADH when rechallenged with
      fluoxetine.

PMID- 11965837
TI  - Case report: Herpes encephalitis.

PMID- 11965838
TI  - Transportational thrombocytopenia.
AB  - Transportational delay in performing a routine CBC may result in platelet
      clumping and a false thrombocytopenia referred to as transportational
      thrombocytopenia.

PMID- 11965839
TI  - A complementary alternative medicine (CAM) medical school curriculum.

PMID- 11965840
TI  - The Hawaii Tumor Registry: more than forty years of cancer surveillance for the
      islands.

PMID- 11965841
TI  - [Hantavirus in human and rodent population in an endemic area for hantavirus
      pulmonary syndrome in Argentina].
AB  - This paper analyzed the prevalence and distribution of serological reactivity to
      hantavirus (antibody against ANDES virus) of human population exposed to
      hantavirus and rodents trapped in the studied area. This study was developed in
      Salta (Oran and San Martin Departments), area with the highest incidence for
      Hantavirus Pulmonary Syndrome (HPS) in Argentina. In December 1997, 453 healthy
      people were studied by serology and 39 rodents by serology and PCR. The studied
      individuals were distributed as: 145 farm inhabitants (FI), 212 people living in
      the same dwelling with healthy individuals (controls) (Cco), 87 people living in
      the same dwelling with persons undergoing SPH in 1997 (cases) (Cca). Moreover, 19
      physicians and nurses who cared for patients with SPH in 1997 were also studied.
      The prevalence of hantavirus infection among the studied population was 6.3%. The
      prevalence was 10.3% among FI, 6.9% among Cca and 3.3% among Cco (p < 0.02).
      There was no serological reactivity among PS. The prevalence in 39 trapped
      rodents was 10.2%, with infection only for Oligoryzomys chacoensis, O. flavescens
      and Akodon varius species. The prevalence of human cases with asymptomatic
      infection in Salta is higher than in other regions of the country, and we are
      presenting a hypothesis to explain these differences. The analyzed data suggest
      that in this region up to the time this study was performed, there would not have
      been person to person transmission of hantavirus. The transmission would be from
      rodent contact exclusively and mainly in ongoing deforestation areas and domestic
      habitat surrounding rural dwellings.

PMID- 11965842
TI  - [Microbiological study of vaginitis and vaginosis in sexually active women].

PMID- 11965843
TI  - [Effect of age on CD4+ cells regeneration in patients with hiv infection
      undergoing triple antiretroviral therapy].

PMID- 11965844
TI  - [Clinical and epidemiological study of adult patients with positive blood
      cultures].
AB  - A cohort evaluation of the microbiology, epidemiology and outcome of adult
      patients with positive blood cultures was performed on 336 patients, from July
      1997 to March 2000. Data for mortality were obtained from 328 of these patients.
      The six most common pathogens were Staphylococcus aureus: 81 (23.5%), coagulase
      negative staphylococci: 50 (14.5%), Escherichia coli: 48 (14.0%), Streptococcus
      pneumoniae: 30 (8.7%), enterococci: 19 (5.5%) and Pseudomonas aeruginosa: 19
      (5.5%). In 169 episodes infections were hospital-acquired and community-acquired
      in the remaining 159. Main infection foci included the respiratory and urinary
      tracts. Infection associated mortality was 33.2%; 29.6% of patients received
      inappropriate empiric antibiotic treatment. Univariate analysis showed that an
      age of 70 or more years, a systemic inflammatory response syndrome (SIRS) score
      higher than 2, a polimicrobial episode, certain foci (abdominal, respiratory or
      unknown), and an inappropriate empiric antibiotic treatment influenced outcome.
      By multivariate analysis the variables that influenced death by infectious cause
      were age of 70 or more years, a SIRS score higher than 2, certain foci
      (abdominal, respiratory or unknown), and an inappropriate empiric antibiotic
      treatment. SIRS score was useful to predict the positivity of the blood culture.
      No relation between outcome and presence of underlying disease, isolation of Gram
      negative microorganism and nosocomial vs. community acquired episode was observed
      (univariate analysis). In order to improve outcome in bacteremic patients, after
      performing cultures of blood and other relevant clinical foci, prompt and
      appropriate antibiotic treatment remains critical. Microbiologic, clinical and
      epidemiological information results crucial for the management of this critically
      ill population.

PMID- 11965845
TI  - [Primary resistance of Mycobacterium tuberculosis in 30 health institutions of El
      Salvador. A pilot study].
AB  - In view of the worldwide re-emergency of tuberculosis (TB) and the rise of
      pulmonary TB (TBP) resistant to the two main first line drugs, namely isoniazid
      (H) and rifampin (R), so called multidrug resistant TBP (MDR-TBP), it was
      considered necessary to carry out a national, non randomized, multicenter,
      prospective pilot survey to determine the rates of resistant Mycobacterium
      tuberculosis (MTB) in patients with no previous antituberculous treatment
      (primary resistance). A total of 30 health institutions were chosen (disseminated
      among the 14 districts of the country) with the most TBP cases reported in 1997,
      and asked to provide in a consecutive non random way, sputum samples from new
      smear positive TB patients starting the first working week of January until the
      last one of December 1998; these samples were processed for culture at the
      Tuberculosis Section of the Health Ministry Central Laboratory. Those that
      resulted positive for MTB underwent a test for resistance to the first line drugs
      used in this country (isoniazid, rifampin, pyrazinamide, ethambutol and
      streptomycin). A total of 348 MTB positive samples were collected. The rate of
      primary resistance to at least one drug was 3.3% and to H it was 0.3%, being
      these rates among the lowest in Latin America. For this reason further studies
      comprising the whole universe of new and already treated smear positive TB
      patients are to be performed in order to determine more accurately the primary
      resistance and acquired rates.

PMID- 11965846
TI  - [Gadodiamide and carbon dioxide as alternative contrast media in patients with
      chronic renal failure].
AB  - Twelve diagnostic and therapeutic angiograms were performed in 10 patients with
      chronic renal failure using gadodiamide and CO2 as vascular contrast. Renal
      function was evaluated with serum creatinine levels 24 hours before and 24 to 48
      hours after the vascular procedure. Imaging quality and tolerance of these
      contrast agents were also studied. There was no significant increase in serum
      creatinine levels in the 12 procedures. In all cases but one, the combined use of
      gadodiamide and CO2 offered images of enough quality and definition for diagnosis
      and therapy. A good symptomatic tolerance was present in all procedures.
      Gadodiamide and CO2 seem to represent useful and safe contrast agents for
      angiography and endovascular intervention in patients with chronic renal failure.
      Further experience is needed to confirm these initial findings.

PMID- 11965847
TI  - [Prevalence of intestinal helminthiasis in primary school children in Santa Fe
      city].
AB  - The aims of this work were: 1.--to determine the intestinal helminth prevalence
      in children who live and attend primary schools in Santa Fe city. 2.--to
      characterize the socio-cultural and sanitary aspects of the children studied and
      consequently to group them in three supposed strata (hypo, meso and
      hyperendemic). The study was carried out during 1998. Considering the following
      variables: kind of streets, sewers and water supplies, parents' educational
      levels, satisfied or unsatisfied basic needs, the city was divided in three
      strata, according to the intestinal helminthic prevalence expected: 1-
      hypoendemic (< 25%), 2--mesoendemic (25-75%) and 3--hyperendemic (> 75%). Schools
      with children of both sexes, and ages between 5 and 13 who belonged to each one
      of the supposed strata, were identified. A direct parasitic examination and a
      Kato Katz technique were performed on a stool specimen of each selected child. An
      epidemiological survey was answered by the children's parents. The prevalence of
      helminths and geohelminths, with 95% confidence intervals, were respectively:
      total sample (n = 163). 36.2% and 34.4%; stratum 1 (n1 = 60) 0% and 0%; stratum 2
      (n2 = 70) 41% (29.9-52.9) y 38.6% (27.2-50.0) and stratum 3 (n3 = 33) 91% (81.1
      100) and 87.9% (76.6-99.2). The above-mentioned variables, related to the socio
      cultural and sanitary aspects, allowed to identify three well defined strata:
      hypoendemic, mesoendemic and hyperendemic, according to the different helminth
      prevalence detected among pupils who attend primary level school in Santa Fe
      city.

PMID- 11965848
TI  - [Inclusion body myositis. Report of 4 cases].
AB  - Inclusion body myositis (IBM) is a primary inflammatory myopathy characterized by
      an older age at presentation. We describe four IBM cases fulfilling Mendell's
      diagnostic criteria. All patients were older than 60 years at diagnosis and the
      mean length of time from onset to diagnosis was 5.7 years. Two of them complained
      of leg weakness with unsteady gait and the other two, of upper limb weakness.
      Three patients had dysphagia, one of them had diaphragmatic paralysis and another
      had bilateral blepharoptosis. Histological sections of the muscle biopsy showed
      mononuclear cell invasion of nonnecrotic muscle fibers, rimmed vacuoles,
      intracellular amyloid deposits and 16-21 nm tubulofilaments by electron
      microscopy. Mitochondrial anomalies were found in two cases. Only one patient had
      transient response to steroid therapy. Our serie shows that clinical presentation
      of inclusion body myositis includes a broader spectrum than the classical
      description.

PMID- 11965849
TI  - [Predictive response variables to recombinant human erythropoietin treatment in
      patients with anemia and cancer].
AB  - The use of human recombinant erythropoietin (rHuEpo) has been approved by the
      Food and Drug Administration (FDA) in patients with anemia and cancer. Although
      good results have been obtained, it is too expensive to permit its use massively.
      For the purpose of evaluating the therapeutic effect of rHuEpo, including
      toxicity, predictive response variables and quality of life parameters, a
      prospective trial was carried out in patients with anemia and cancer.
      Hematimetric parameters, ferritin, Epo, cytokines, transfusions and quality of
      life were registered. A total of 36 patients were treated in the protocol (34
      were evaluable): 16 men and 20 women, with a medium age 56.4 years; 27 patients
      were treated with chemotherapy (16 with cisplatinum); 15 patients presented
      medullar infiltration. In 73.5% patients an increase in the level of hemoglobin
      was registered, and in 64.7% its normalisation was attained. Transfusional
      requirements were reduced by 50%. The hemoglobin increase greater than 0.5 g/dl
      at the second week of treatment was the most significant variable of early
      response. Patients treated with cisplatinum, seric ferritin lower than 1,100
      ng/dl and those without medullar tumoral infiltration responded best. Serum Epo,
      cytokines (IL-1, IL-6 and TNF) and reticulocyte count at the second week did not
      correlate with response. Quality of life parameters were better in patients with
      good response to rHuEpo. It can be concluded that good results in the treatment
      of patients with anemia and cancer are obtained with rHuEpo.

PMID- 11965850
TI  - [Cadasil: a case with molecular diagnosis].
AB  - CADASIL disease (Cerebral Autosomal Dominant Arteriopathy with Subcortical
      Infarcts and Leukoencephalopathy) was described in 1991 by Tourmier-Lasserve. Two
      years later the same authors described its association with chromosome 19;
      nonetheless, the mutations in gene Notch3 were not described until 1996. Clinical
      findings depend on the age at onset. The early form of the illness is found in
      young patients, generally less than 30 years old, and the main clinical
      manifestation is a migraine headache with subcortical lesions in the white
      matter, while in the later form ischemic events and behavioral symptoms are
      predominant. Anatomo-pathological findings in CADASIL include the presence of
      osmophilic granular deposits in vessel walls, skin, muscles and cerebral
      arteries. We present a patient with CADASIL and cavernous angioma. We studied a
      40-year-old woman who underwent surgery for a left temporal-parietal cavernous
      angioma, with aphasia as the only symptom, two years before admission. Her family
      history showed that her father had suffered from vascular dementia. She was
      admitted to our hospital with right-side hemiparesis and dysarthria. A CT scan
      showed the presence of ischemic vascular lesions and former surgery sequelae. The
      duplex scan of the neck vessels and a transesophageal echocardiogram ruled out an
      embolic source. Laboratory tests including VDRL, HIV, prothrombotic profile and
      rheumatologic screening tests were normal. An MRI in T2W and FLAIR showed the
      presence of multiple subcortical cerebral lesions and hyperintensity in the white
      matter (leukoencephalopaty). We found a left acute putaminal-capsular infarct in
      the diffusion-MRI. The MRA was normal. Analysis of the cerebrospinal fluid was
      unremarkable. A molecular DNA test was performed, and a nucleotide substitution
      in position 583 in exon 4 of gene Notch3 was detected. This mutation was found
      only in CADASIL patients. The association with cavernous angioma has not been
      previously reported, and we believe that it was unrelated to CADASIL, either
      clinically or genetically. To our knowledge, this is the first case of CADASIL
      diagnosed by molecular DNA test in our country.

PMID- 11965851
TI  - [Abdominal distension due to herpes zoster].
AB  - A case is reported in which an abdominal protrusion appeared in relation with a
      zosteric eruption at 11th dorsal dermatome. The motor deficit in zoster is
      unusual (2-3% in the reported series) and generally recognized when the
      extremities are affected. The frequency with which the abdominal muscles are
      involved is estimated to be around 0.17%, according to a clinical series. The aim
      of this report is to draw attention to the abdominal wall paresis that can result
      when zoster involves the caudal dorsal dermatomyotomes. This in turn, leads to
      abdominal distension which needs to be differentiated from other causes.

PMID- 11965852
TI  - [Tc-99m methylene diphosphate (MDP) estra osseous uptake in a patient with
      hypercalcemia and secondary hypoparathyroidism].

PMID- 11965853
TI  - [Pulmonary arterial sequestration].

PMID- 11965854
TI  - [Menopausal transition, physiopathology, clinical and treatment].
AB  - Menopausal transition is a period that begins four years before menopause as a
      result of follicular decline. The first hormonal change is a decrease in B
      inhibin levels, followed by a decrease in estradiol and an increase in FSH
      levels; abrupt plasmatic oscillations of these hormones can be observed.
      Climacteric symptomatology may appear before cycle disorders and provoke an
      impairment in quality of life. Bone loss equally precedes menopause. Some
      authors, but not all of them, accept that during perimenopause there is an
      increased risk of cardiovascular disease. We point out the need of beginning
      hormonal therapy when the first clinical signs of estrogenic deficiency arise,
      independent of menstrual cycle and hormonal levels. Women aged over 45 are
      suitable for the classical sequential therapy, adjusting it to the cycle while it
      still persists; younger patients may use transdermal estrogens for short periods
      of time. Whenever contraception is required or there is irregular bleeding we
      indicate low dose estrogenic contraceptives, if possible the 28 days of the
      cycle. It is necessary to correct potentially dangerous daily habits and treat
      concomitant diseases that may enhance cardiovascular risk. The patient's
      education is an indispensable goal for the success of the treatment.

PMID- 11965855
TI  - [Therapeutic applications of pore-forming lytic toxins: potential use of
      Escherichia coli alpha-hemolysin].
AB  - Many infectious bacteria export soluble proteins which can damage the plasma
      membrane of eukaryotic cells. Most often they are directed against leukocytes for
      the purpose of reducing the immune response of the host. In some cases, these
      toxins are also hemolytic. It has been proposed that both leukotoxic and
      hemolytic activities could derive from the pore formation in the membranes of the
      attacked cells. The study of these molecules is not only important from the point
      of view of basic studies to determine the mechanism of action, but also for
      potential application in biotechnology and medicine. These molecules increase the
      cell susceptibility to chemotherapy and also can be employed to destroy
      specifically cancer cells. On the other hand, it is possible to incorporate toxin
      molecules in liposomes, transforming them in to biosensors or as controlled drug
      delivery systems. This aspect has not been extensively explored in Escherichia
      coli alpha-hemolysin, in which the presence of different functional and
      structural domains in this molecule could be taken advantage of.

PMID- 11965856
TI  - [Tumor markers in breast neoplasm].
AB  - Breast cancer is the most frequently diagnosed cancer among women in the western
      world. In spite of a great deal of scientific information in relation to its
      origin, of new diagnostic methods and treatments, mortality rate due to breast
      cancer has virtually remained stable over the past 20 years. Recent advances in
      molecular biology have improved the understanding of the basic biology of breast
      cancer. This fact has led to the identification of new tumor markers the ultimate
      goal of which is to reduce mortality by identifying women at risk as well as
      predicting the prognosis of existing disease and the response to different
      therapies. This article focuses on both traditional and new molecular markers,
      their clinical utility and their relevance in the routine evaluation of patients
      with breast cancer.

PMID- 11965857
TI  - [Poisoning by spiders of Loxosceles genus].
AB  - Despite the great number of spiders in the world, only a small group of them is
      capable of producing death in humans. In Argentina, there are only three of the
      four genera of spiders considered of high risk to humans: Latrodectus is present
      in rural areas, Phoneutria is restricted to small regions while Loxosceles is
      distributed throughout the country. Accidents by Loxosceles represent around 4%
      of the total number produced by venomous animals in Argentina. The bite is
      accidental and may produce considerable local necrosis with scar formation and
      ulcers of slow and difficult healing that may require surgical repair. Some
      bitten people may suffer from intravascular hemolysis, disseminated coagulation
      and acute renal insufficiency leading to death. Despite the great number of
      studies performed on Loxosceles venoms, at present, the physiopathological course
      of poisoning is not clear and there is not common criteria for its treatment. In
      this review, biological and epidemiological data of this spider are described as
      well as the venom composition and the possible participation of its components in
      the poisoning. These data provide biological and biochemical tools to understand
      the course of poisoning and to have better criteria for the treatment and
      prevention of these accidents and their complications.

PMID- 11965858
TI  - [Human herpesvirus-6 circulation in healthy adults and oncologic patients].
AB  - The aim of this paper was to assess the prevalence of antibodies to HHV-6 in the
      general population and study the virus circulation among individuals with cancer,
      in order to analyze HHV-6 involvement in lymphoproliferative disorders. A total
      of 200 sera from the general population and 67 from patients with neoplasia were
      studied. The latter were divided in 3 groups: lymphoma/myeloma, leukemia and non
      immune solid tumors. HHV-6 antibodies (IgG and IgM) were assayed by IFA and viral
      genomes were detected using nested PCR. The prevalence of the infection in the
      healthy population was 63.5% with a titer geometric mean (TGM) of 48.67 +/- 1.23.
      A control group was obtained by systematic sampling of the healthy population.
      Among the patients with neoplasia, the prevalence was 95.5%. In the
      lymphoma/myeloma group, TGM was 268.73 +/- 1.62; in the leukemia group it was
      151.1 +/- 1.88 and in the non-immunogenic solid tumors group it was 95.67 +/-
      1.57. Statistically significant differences were observed (p < 0.01) between the
      control group and the lymphoma/myeloma and leukemia groups. Serum IgM or free
      viral genomes were not detected in any serum sample. The antibody prevalence
      found in the general population documents the high circulation of this
      lymphotropic virus which could indirectly contribute to the pathogenesis of the
      lymphoproliferative disorder.

PMID- 11965859
TI  - [Pain].

PMID- 11965860
TI  - [Adjuvant factors in DNA vaccines].

PMID- 11965902
TI  - [Use of modern technologies and designing means for development of automated
      information systems for military medicine].
AB  - At present time, the intensive activity implementation of automated information
      systems (AIS) to the military medical establishment are observed. From design
      quality the successful functioning of the AIS depend on. The effective
      functioning and the interaction of the automated information technologies by
      specialists, which computers and telecommunications use for performance of the
      their purpose, are a goal of the design. Today, there are two classes"
      technologies for designing of the automated information systems of military
      medical application: conventional technology and integrated instrumental means
      technologies. In this article, the conventional technology and integrated
      instrumental means technologies are considered more detail. CASE-technologies
      (the functional-oriented and object-oriented approaches) and RAD (Rapid
      Application Development) are viewed.

PMID- 11965861
TI  - NTP Technical Report on the Toxicology and Carcinogenesis Studies of Chloral
      Hydrate (Cas No. 302-17-0) in B6C3F1 mice (Gavage Studies).
AB  - Chloral hydrate is used medically as a sedative or hypnotic and as a rubefacient
      in topical preparations, and it is often given to children as a sedative during
      dental and other medical procedures. Chloral hydrate is used as a central nervous
      system depressant and sedative in veterinary medicine and as a general anesthetic
      in cattle and horses. It is a byproduct of the chlorination of water and has been
      detected in plant effluent after the bleaching of softwood pulp. Chloral, the
      anhydrous form of chloral hydrate, is used as a synthetic intermediate in the
      production of insecticides and herbicides. Chloral hydrate was nominated for
      study by the Food and Drug Administration based upon widespread human exposure
      and its potential hepatotoxicity and the toxicity of related chemicals. One goal
      of the study was to assess the effect of the animal's age and the duration of
      dosing on the tumorigenicity of chloral hydrate. Beginning on postnatal day 28,
      female B6C3F1 mice received chloral hydrate (99.5% pure) in water by gavage for
      3, 6, or 12 months, 2 years, or as a single dose; on postnatal day 15, male and
      female B6C3F1 mice received a single dose by gavage. Tumorigenicity was assessed
      for 2 years after the initial dose. Genetic toxicology studies were conducted in
      Salmonella typhimurium, cultured Chinese hamster ovary cells, Drosophila
      melanogaster, and mouse bone marrow cells. 2-YEAR STUDY Groups of female mice
      (regimens A, B, C, and D) and groups of male mice (regimen E) received chloral
      hydrate in distilled water by gavage; control groups received distilled water
      only. In regimen A, groups of 48 female mice received 0, 25, 50, or 100 mg
      chloral hydrate/kg body weight 5 days per week for 104 weeks beginning when they
      were 28 days old. In regimen B, 24 female mice received 0 mg/kg and three groups
      of 48 female mice received 100 mg/kg 5 days per week beginning when they were 28
      days old. Eight mice from the 0 and 100 mg/kg groups were killed at 3, 6, or 12
      months. The remaining mice were held without dosing for the duration of the 2
      year study. In regimen C, groups of 48 female mice received a single dose of 0,
      10, 25, or 50 mg/kg when they were 28 days old and were held for 104 weeks. In
      regimens D and E, groups of 48 female and 48 male mice, respectively, received a
      single dose of 0, 10, 25 or 50 mg/kg when they were 15 days old and were held for
      104 weeks. Additional groups of four mice from regimens C, D, and E and mice
      killed at 3 or 6 months from regimen B (eight mice per group) were designated for
      hepatic cell proliferation analyses; mice killed at 3 or 6 months in regimen B
      were also designated for apoptosis analyses. Survival and Body Weights Survival
      of all dosed mice in all regimens was similar to that of the vehicle control
      groups. Mean body weights of 100 mg/kg female mice in regimen B dosed for 3 or 6
      months were generally greater than those of the vehicle controls during the
      second year of the study. Mean body weights of 25 mg/kg male mice in regimen E
      were generally less than those of the controls beginning at week 19; mean body
      weights of 10 and 50 mg/kg mice were generally less than those of the vehicle
      controls beginning at week 80. Pathology Findings A dose-related and significant
      increase in the incidence of pars distalis adenoma occurred in regimen A 100
      mg/kg females. There was also a time-related increase in the incidence of adenoma
      in female mice administered 100 mg/kg for up to 24 months in regimen B, and the
      increase in the incidence of this neoplasm at 24 months was significant. There
      was a significant increase in the severity of pars distalis hyperplasia in
      regimen A 100 mg/kg female mice. GENETIC TOXICOLOGY Chloral hydrate was mutagenic
      in vitro and in vivo. It induced mutations in Salmonella typhimurium strain
      TA100, with and without liver S9 activation; an equivocal response was obtained
      in S. typhimurium strain TA98 in the absence of S9, and no mutagenicity was
      detected with strain TA1535 or TA1537, with or without S9. Chloral hydrate was
      shown to produce chromosomal damage in mammalian cells. It induced significant
      increases in sister chromatid exchanges and chromosomal aberrations in cultured
      Chinese hamster ovary cells, with and without S9. Results of sexlinked recessive
      lethal (SLRL) tests in Drosophila melanogaster were inconclusive. Chloral
      hydrate, administered by feeding, produced an inconclusive increase in SLRL
      mutations in the germ cells of male flies. Results of an in vivo mouse bone
      marrow micronucleus test with chloral hydrate were positive. CONCLUSIONS Under
      the conditions of this 2-year gavage study, there was equivocal evidence of
      carcinogenic activity of chloral hydrate in female B6C3F1 mice treated
      continuously for two years based on increased incidences of pituitary gland pars
      distalis adenomas. No increased incidences of neoplasms were seen in female
      B6C3F1 mice that received a single dose of chloral hydrate at 15 or 28 days of
      age or in male B6C3F1 mice that received a single dose of chloral hydrate at 15
      days of age. No hepatocarcinogenicity was seen under any dosing condition.

PMID- 11965904
TI  - [Characteristics of studying and demonstrating hazardous effects of tobacco
      smoking in experiment].
AB  - Modern medicine considers the tobacco smoking to be the chronic poisoning that
      has the mass character. The experience of many years shows that sanitary-and
      educational measures explaining the injurious effect of tobacco smoking in some
      cases give no positive results. Convincing pedagogical influence together with
      experimental investigations make the struggle against smoking more effective. Use
      of the portable personal device "Manual on medicine" reveals the mechanism of
      protective action of filtering materials and demonstrates the clinical picture of
      acute intoxication caused by toxic gases of tobacco smoke.

PMID- 11965903
TI  - [Toxicomania in servicemen].
AB  - The authors substantiate the urgency of toxicomania among the servicemen. The
      circumstances of toxicomania, its morphological manifestations, toxic agents used
      by the toxic substance addicts were analyzed using the materials of 98
      observations from medicolegal practice with lethal outcome. The measures to
      prevent and diagnose the toxicomania are proposed.

PMID- 11965905
TI  - [Clinical efficacy of plasmapheresis in therapy of macrofocal myocardial
      infarction complicated with post-infarction angina pectoris].

PMID- 11965906
TI  - [Phacoemulsification of complicated traumatic cataracts].
AB  - Results of surgical treatment 142 eyes of patients with traumatic cataracts
      complicated with accompanied pathology (corneal scars, anterior and posterior
      synechia, lens subluxation, anterior and posterior capsule defects and others)
      are analyzed. In 107 cases phacoemulsification was done, in other cases-
      lensectomy, intracapsular extraction or phacoaspiration of traumatic cataract.
      Indications and contraindications for traumatic cataract phacoemulsification are
      formulated.

PMID- 11965907
TI  - [Ischemic abdominal syndrome].

PMID- 11965908
TI  - [Clopixol: new possibilities in therapy of mental disorders (a review of clinical
      studies)].

PMID- 11965909
TI  - [Theory of medical service management: establishment and development].

PMID- 11965910
TI  - [Improvement of technical support for special medical detachments].

PMID- 11965911
TI  - [Development of thoracic surgical procedures in N N Burdenko Main Military
      Clinical Hospital and the State Institute for Advanced Medical Education of
      Ministry of Defense of Russian Federation].

PMID- 11965912
TI  - [V N Shevkunenko--a prominent topographoanatomist and surgeon].

PMID- 11965913
TI  - [Problems of survival from alimentary dystrophy and psychoemotional stress during
      Leningrad blockade (Part 2)].

PMID- 11965915
TI  - [Methodological basis for development of basic software for automation of
      military medical institutional activity].

PMID- 11965916
TI  - Retroviruses conference reassuring on new treatments, viral targets, research.

PMID- 11965917
TI  - Lipoatrophy and antiretroviral drug changes.

PMID- 11965918
TI  - Retroviruses conference: Web coverage.

PMID- 11965919
TI  - d4T and lactic acidosis with neuromuscular weakness: FDA warning.

PMID- 11965920
TI  - FDA approves new dosing for amprenavir and ritonavir combination.

PMID- 11965921
TI  - FDA approves once-daily efavirenz formulation, revised labeling.

PMID- 11965922
TI  - Can treatment during primary HIV infection lead to control of disease without
      drugs?
AB  - Initiating antiretroviral treatment during PHI, particularly in the acute phase
      (before seroconversion), appears to interrupt the natural history of HIV
      infection in the host. Although all the parameters of such an interruption are
      not understood, what remains clear is that a condition can be induced where the
      host is better able to control viremia in the absence of therapy. Structured
      treatment interruptions, therapeutic vaccines, and other novel mechanisms may
      further enhance HIV-specific immunity and viral suppression. The duration of such
      effects, their outcome on survival, and how they apply to chronic infection are
      not known. However, just as the study of long-term nonprogressors has provided
      valuable information about host-virus interactions, so too may the study of
      induced host control of viremia lead to improved therapeutic approaches and
      perhaps one day a functional cure.

PMID- 11965923
TI  - Primary HIV infection case presentations.
AB  - The following cases illustrate the complexities involved in recognizing and
      correctly diagnosing primary HIV infection (PHI). Extensive lab work, but also
      thorough history taking, is required. Patient 1 was not recognized as suffering
      from PHI until after she was discharged from the hospital. Patient 2 was
      recognized with PHI, and his symptoms spontaneously resolved. Patient 3 required
      extensive hospitalization because of pulmonary complications. Viral loads
      declined sharply without medication for both patients 1 and 2, upon resolution of
      symptoms. However, patient 3 maintained a high viral load and was started on
      triple-drug antiretroviral therapy. None of the patients were started on
      antiretroviral therapy during the acute retroviral syndrome phase of PHI, which
      is currently recommended in US treatment guidelines.

PMID- 11965924
TI  - Nursing assessment of the patient with primary HIV infection: key to improving
      clinical recognition.
AB  - David is a 29-year-old Hispanic male who presents complaining of fatigue,
      headache, muscle aches, a sore throat, and nausea. Physical assessment
      demonstrates an erythematous maculopapular rash on the trunk and symmetric
      adenopathy. His temperature is 37.6 degrees C; other vital signs are within
      normal limits. Laboratory findings include a white blood cell count of 4.5/microL
      and a platelet count of 98,000/mm3. Blood chemistry is unremarkable. David states
      that his symptoms began one week ago.

PMID- 11965925
TI  - Treatment during PHI as a method of altering the epidemic spread of HIV.

PMID- 11965926
TI  - The acute infection and early disease research program.

PMID- 11965927
TI  - Psychological issues in patients with PHI.

PMID- 11965928
TI  - Backgrounder: recognizing and diagnosing primary HIV infection.

PMID- 11965929
TI  - Palliative cancer patients and their families on the Internet: motivation and
      impact.
AB  - Increasingly, palliative patients and their families are going online. A series
      of cases are presented to explore the reasons they go online and the effects of
      their online activity, both harmful and beneficial. This paper highlights the
      need to take this growing phenomenon and its effects on patient care seriously,
      and identifies key areas that need to be explored further.

PMID- 11965931
TI  - Perceived skills in palliative medicine of newly qualified doctors in the U.K.
AB  - AIM: To ascertain the perceived skills of students at U.K. medical schools in
      palliative medicine. DESIGN: A validated questionnaire survey. PARTICIPANTS:
      Newly qualified U.K. pre-registration house officers (PRHOs). MEASURES: A Likert
      scale from 0 to 5 for respondents to rate their perceived skills in four clinical
      scenarios, and their anxiety in caring for the dying. RESULTS: Mean confidence
      rating in breaking bad news was 2.9, in ability to empathize was 3.2, in
      discussing prognosis was 3.3, and in providing symptom control was 2.8. Mean
      anxiety rating in caring for a dying patient was 2.9. Of the comments, 24% wished
      for more "hands on" experience and 23% suggested further curriculum
      recommendations. CONCLUSION: Teaching of palliative medicine is still inadequate
      for the needs of recently qualified doctors. Although PRHOs have identified a
      need for further instruction there is also acknowledgment that it is a difficult
      subject to teach. Recommendations are made for coordination of current
      interdepartmental teaching programs.

PMID- 11965930
TI  - Referral of terminally ill patients for hospice: frequency and correlates.
AB  - BACKGROUND: Despite the central role of hospice in end-of-life care, little is
      known about the proportion of terminally ill patients referred for hospice and
      the physician factors associated with hospice referral. METHODS: Cross-sectional
      data from a self-administered survey of 231 physicians were used to estimate the
      proportion of terminally ill patients who were referred for hospice and to assess
      the independent effects of physician factors on hospice referral. RESULTS: On
      average, physicians reported referring about 55% of their terminally ill patients
      for hospice; 26.7% of the physicians referred less than one quarter of their
      terminally ill patients. Physician specialty, board certification, and
      physicians' knowledge level about hospice were independently associated with the
      proportions of terminally ill patients referred for hospice. CONCLUSION: Many
      terminally ill patients are not referred for hospice care and physician factors
      influence the use of hospice significantly. The study suggests effective factors
      and groups to target with interventions to enhance the appropriate use of
      hospice.

PMID- 11965932
TI  - Who really knows how to die?

PMID- 11965933
TI  - Palliative care crises in the community: a survey.
AB  - With the rising age of the population, hospital cutbacks, and increased attention
      to home-based care for the dying, the community can expect to experience more
      intense care situations and a greater potential for palliative care crises
      developing in the home setting. Whether the crisis is precipitated by hemorrhage,
      severe uncontrolled pain, or agitation, the demands placed on the family unit and
      careprovider can be phenomenal. Only with a greater awareness of the difficulties
      encountered in the home setting can the community begin to respond to the needs
      of the family in crisis. An open-question survey regarding palliative care crises
      in the community was conducted among community visiting RNs, home care case
      managers, and palliative outreach clinicians in southwestern Ontario, The
      objectives were: 1) to determine the pattern of events that precipitated a
      crisis; 2) to understand how crises were managed; 3) to identify barriers to
      effective crisis management; 4) to investigate the impact on the family unit and
      careprovider. Participants were also asked to list the essential resources they
      needed to deal effectively with a crisis situation. This paper highlights the
      results of the survey and suggests implications for the future direction of
      palliative care in the home.

PMID- 11965935
TI  - End-of-life care for seniors: the development of a national guide.

PMID- 11965934
TI  - Supportive care: palliative care in children, adolescents, and young adults-
      model of care, interventions, and cost of care: a retrospective review.

PMID- 11965936
TI  - Assessing the need for and potential role of a day hospice: a qualitative study.
AB  - We conducted a qualitative case study as part of a needs assessment for a day
      hospice in a small Ontario city. Data were gathered from semi-structured
      interviews with 28 stakeholders: nine health care administrators, 11 health care
      providers, and eight lay people (terminally ill adults and informal caregivers).
      Respondents described support, counselling, social activities, and respite as key
      day hospice services. They also described several barriers to accessing services,
      including location, transportation, admission criteria, referrals, and fees. For
      most respondents, the ideal staff mix includes both volunteers and paid
      professionals in either a free-standing organization or institutionally linked
      hospice. Although the vast majority of participants were reluctant to impose
      admission criteria or other limitations on hospice clientele, they expressed the
      need to ensure equitable access to this scarce resource. Opinions varied greatly
      across stakeholder groups, highlighting the need to collect information from all
      relevant stakeholder groups when planning hospices.

PMID- 11965938
TI  - Re: Perception of discomfort among relatives of unresponsive terminally ill
      patients.

PMID- 11965937
TI  - Concerns of Japanese hospice inpatients about morphine therapy as a factor in
      pain management: a pilot study.

PMID- 11965939
TI  - Quest for healthy alternatives.

PMID- 11965940
TI  - Are they eating properly? Now you can tell.

PMID- 11965941
TI  - Scotland. Break for the border.

PMID- 11965942
TI  - Staff shortages push homes to the brink.

PMID- 11965943
TI  - Is the clinical nurse specialist deskilling the general nurse?

PMID- 11965944
TI  - Holding our hands up.

PMID- 11965945
TI  - There is no sound basis for ADHD.

PMID- 11965947
TI  - Dead end for learning disabilities.

PMID- 11965946
TI  - Raw deal for nurse prescribers.

PMID- 11965948
TI  - Lavender for migraine, but holism works even better.

PMID- 11965949
TI  - Cleaning up is no Mickey Mouse job.

PMID- 11965950
TI  - Curtain up in theatres.

PMID- 11965952
TI  - Resident gain.

PMID- 11965951
TI  - Sitting pretty.

PMID- 11965953
TI  - Norse-led protest stubs it out.

PMID- 11965954
TI  - Mental health. Risky business.

PMID- 11965955
TI  - Money talks, Mr Milburn, and it could also help you to deliver.

PMID- 11965956
TI  - Adjuvant treatment for breast cancer patients.

PMID- 11965957
TI  - Using honey dressings: the practical considerations.

PMID- 11965958
TI  - Just typical: the treatment of psychosis in the UK.

PMID- 11965959
TI  - Is knowledge a dangerous thing?

PMID- 11965960
TI  - Tough winter ahead for NHS.

PMID- 11965961
TI  - Working with NHS direct.

PMID- 11965963
TI  - Unions say COLS are first step to 'regionalised pay'.

PMID- 11965962
TI  - Preventing venous leg ulcer recurrence.

PMID- 11965964
TI  - Labour peer doubts safety of advice.

PMID- 11965965
TI  - Deadly risk of drug-resistant HIV.

PMID- 11965966
TI  - All nurses urged to have their say.

PMID- 11965967
TI  - Victory in eviction battle.

PMID- 11965968
TI  - Midwifery. Teamwork is a winner for mothers with greater needs.

PMID- 11965969
TI  - Occupational hazards. Allergic nurse wins 100,000 Pounds.

PMID- 11965970
TI  - Record number of nurses seek adventure overseas.

PMID- 11965971
TI  - Raising the standards.

PMID- 11965972
TI  - What is benchmarking in clinical practice?

PMID- 11965973
TI  - 'I don't smoke now'.

PMID- 11965974
TI  - Euthanasia. Dutch fail to clarify nurses' position in mercy killings.

PMID- 11965975
TI  - Cost-of-living payments. Heads you win.

PMID- 11965976
TI  - Racism. The race is on to beat discrimination.

PMID- 11965977
TI  - Sudden infant death syndrome. Cot hot spots.

PMID- 11965979
TI  - Everyone makes mistakes.

PMID- 11965978
TI  - Coronary heart disease. Beating a killer disease.

PMID- 11965980
TI  - Does the NHS need its own police force?

PMID- 11965981
TI  - Listen to the voice of experience.

PMID- 11965983
TI  - If you want to fill this, pay attention to this.

PMID- 11965982
TI  - HCAs: great nurses at half the price.

PMID- 11965984
TI  - Hysteria over agencies.

PMID- 11965985
TI  - Youth is not to blame.

PMID- 11965986
TI  - The Irish are 'ethnic' too.

PMID- 11965987
TI  - How do you spell 'dumbed down'?

PMID- 11965988
TI  - Honesty is the best policy.

PMID- 11965989
TI  - Agents for change?

PMID- 11965990
TI  - Did nurses aid the Nazis?

PMID- 11965991
TI  - Stress. How to survive in one piece.

PMID- 11965992
TI  - Only openness and honesty in the NHS will do, but it must apply to all.

PMID- 11965993
TI  - Changing health through sexual revolution.

PMID- 11965994
TI  - The surgical management of breast cancer.

PMID- 11965995
TI  - How college nurses managed the meningitis C campaign.

PMID- 11965996
TI  - Illegal drugs. Nurses left open to prosecution.

PMID- 11965997
TI  - Top rating 'too hard' for many.

PMID- 11965998
TI  - Recognising mental health problems in older patients.

PMID- 11965999
TI  - A teaching nursing home.

PMID- 11966000
TI  - Pin-site care.

PMID- 11966001
TI  - Nervous system. 4. System and diseases. Exploring normal anatomy and physiology.

PMID- 11966002
TI  - Honours system. MP attacks 'elitist' gongs.

PMID- 11966003
TI  - Commercial sponsorship. New rules say any gift over 25 Pounds must be declared.

PMID- 11966004
TI  - Professional development. Top nurses to get training worth 4m pounds.

PMID- 11966005
TI  - Critical care. 40% of hospitals have no HDU.

PMID- 11966006
TI  - Experts query benefit of NICE U-turn on flu drug.

PMID- 11966007
TI  - Infection control. Lack of hand-washing 'inexcusable', say MPs.

PMID- 11966009
TI  - Infection control. Scabies outbreak in Kent.

PMID- 11966008
TI  - When nurses connive in misery and folly.

PMID- 11966010
TI  - Giving up smoking is no drag.

PMID- 11966011
TI  - A&E nursing. Waiting to happen.

PMID- 11966012
TI  - Unqualified staff. More work for less pay.

PMID- 11966013
TI  - Abortion. The question of choice.

PMID- 11966014
TI  - Should nurses give medication without the patient's consent?

PMID- 11966015
TI  - The human cost of the care homes crisis.

PMID- 11966016
TI  - Nurses need more support to care for the dying.

PMID- 11966017
TI  - The patients from hell.

PMID- 11966018
TI  - Old before their time.

PMID- 11966019
TI  - Less nitty Nora, more intrepid explorer.

PMID- 11966021
TI  - Nurses need to feel supported when challenging racist behaviour.

PMID- 11966022
TI  - Elective admissions to suit the individual.

PMID- 11966020
TI  - Pills won't cure ills caused by poverty.

PMID- 11966023
TI  - Bone metastasis: secondary illness, primary concern.

PMID- 11966024
TI  - Care of patient with spinal injuries who requires weekly manual evacuations.

PMID- 11966025
TI  - Experience counts.

PMID- 11966026
TI  - Setting up a sexual health clinic in a school.

PMID- 11966027
TI  - Unison set to claim at least 10% pay hike.

PMID- 11966028
TI  - Cardiopulmonary resuscitation. Initial assessment.

PMID- 11966029
TI  - Unions call for firm stand against racism.

PMID- 11966030
TI  - Mental Health. Conflict will cause increase in depression.

PMID- 11966031
TI  - Cancer. 'Empower patients', nurses told.

PMID- 11966033
TI  - New call for safer needles.

PMID- 11966032
TI  - Patient death inquiry. A&E tragedy due to 'systematic failure'.

PMID- 11966034
TI  - Computer gains.

PMID- 11966035
TI  - Care costs. Measure for measure.

PMID- 11966036
TI  - Mental health. Recovery is a state of mind.

PMID- 11966037
TI  - Elderly care. The last resort.

PMID- 11966038
TI  - Is nursing research the key to raising standards of care?

PMID- 11966039
TI  - Abuse can also begin at home.

PMID- 11966040
TI  - Is it acceptable to put surgical beds in the day room?

PMID- 11966043
TI  - Is there a secret to taking the strain?

PMID- 11966044
TI  - An inspector calls.

PMID- 11966045
TI  - The free care minefield.

PMID- 11966046
TI  - A honeypot for abusers.

PMID- 11966047
TI  - What have PCGs and PCTs done for nurses?

PMID- 11966048
TI  - Eating disorders: why do nurses choose this field?

PMID- 11966049
TI  - Collaborative care.

PMID- 11966050
TI  - Vaccines for preventing hepatitis B in health care workers.

PMID- 11966052
TI  - The benefits of tracheostomy specialist nurses.

PMID- 11966053
TI  - Coronary heart disease: 3. The management of unstable angina, myocardial
      infarction, and current challenges.

PMID- 11966054
TI  - Meeting the challenge of infection control.

PMID- 11966055
TI  - A prescription for success.

PMID- 11966056
TI  - Reservoir bugs: sources of hospital-acquired infection.

PMID- 11966057
TI  - A flexible approach to methicillin-resistant Staphylococcus aureus (MRSA).

PMID- 11966059
TI  - Removing the stigma.

PMID- 11966060
TI  - Serum ferritin as a measure of iron stores in the college girls.
AB  - The average daily iron consumption of the college girls was 48 per cent of the
      recommended dietary allowances of ICMR (1990). The Hb level was below the normal
      value. The values of serum iron, transferrin saturation (TS) and unsaturated iron
      bearing capacity (UIBC) were in the normal range but near the lower margin. The
      TIBC was above the normal range. The serum ferritin values showed very poor iron
      stores. A highly significant (p < 0.01) correlation was observed between Hb,
      serum iron and TS with serum ferritin. There is a superiority of ferritin over
      other blood parameters as it indicates the liver iron stores, hence, a better
      predictor of iron deficiency status.

PMID- 11966061
TI  - Prevalence of hypertension in Mumbai.
AB  - There are few reports on prevalence of hypertension in India. We are presenting a
      study of its incidence in OPD of hospital patients in Mumbai. Prevalence of
      hypertension was 7.82% in all subjects, however, it was higher in females 10.5%
      than in males 6.1%.

PMID- 11966062
TI  - Effect of single dose of prednisolone on hospitalisation in patients of acute
      bronchial asthma.
AB  - The present study was undertaken to assess the effect of stat dose of oral
      prednisolone on rate of hospitalisation in patients of acute bronchial asthma.
      259 patients, aged 1-65 years presenting with acute exacerbation of asthma were
      randomised in a double blind fashion to receive a stat dose of oral prednisolonev
      (30 mg if age < 5 years; 60 mg if age > 5 years) or equivalent placebo. Then,
      nebulbutamol (0.15 mg/kg in 2 m/l normal saline) was given to all patients and
      patients were re-examined after 4 hours to decide about the hospitalisation. The
      study revealed that only 37 (26.42%) patients required hospitalisation and
      further management in prednisolone group compared to 50 (42.01%) patients in
      placebo group (p < 0.01). This suggests that prompt use of single oral dose of
      prednisolone along with routine bronchodilator therapy can significantly reduce
      morbidity and need for hospital admission in patients of acute bronchial asthma.

PMID- 11966063
TI  - Emerging antibiotic resistance among the uropathogens.
AB  - A total of 18,876 urine samples from patients of clinically suspected UTI
      including asymptomatic pregnant females were analysed, during the year 1997 &
      1998. Culture positivity rate was found to be 37%. The incidence of Proteus was
      on the rise during the year 1998 especially in hospitalized patients. The
      antibiotic sensitivity pattern of uropathogens was also analysed to check the
      emergence of drug resistance. This study has revealed that withdrawal of a
      particular antibiotic due to high level of resistance observed during previous
      years, has led to re-emergence of antibiotic sensitive mutants. Further
      indiscriminate use of newer antibiotics like amikacin and netilimicin is
      responsible for emergeny of resistant variant against these antibiotics and this
      lays stress upon the immediate need for national antibiotic policy.

PMID- 11966064
TI  - Is hysteria still prevailing? A retrospective study of sociodemographic and
      clinical characteristics.
AB  - A retrospective study was conducted in a psychiatric setup of S.P. Medical
      College, Bikaner (Raj.) to assess the social demographic and clinical
      characteristics of hysterical patients. The illness was more common in female
      patients. Most of the patients were young, married and illiterate. Nearly half of
      them had faced some stress prior to onset of their illness. Fits of
      unconsciousness and aphonia were the commonest presentation in female and male
      patients respectively. Duration of stay was 2-3 days and most of the patient
      responded well to different treatment modalities.

PMID- 11966065
TI  - Lung cancer with skin metastasis--case report.

PMID- 11966066
TI  - Symptoms of aging tied to brain chemistry.

PMID- 11966068
TI  - Still waiting for an improvement in A&E services.

PMID- 11966067
TI  - Scientists uncover new clues about ageing.

PMID- 11966069
TI  - Nurse practitioners are 'missed opportunity'.

PMID- 11966070
TI  - Midwifery. RCM calls it a day on night rate.

PMID- 11966071
TI  - Coronary care. The heart beat.

PMID- 11966072
TI  - Private finance initiative. At the top of a slippery slope?

PMID- 11966073
TI  - Is partnership with GPs the way forward for practice nurses?

PMID- 11966074
TI  - Testing times for nurses everywhere.

PMID- 11966075
TI  - Just an accident waiting to happen.

PMID- 11966076
TI  - Beacon of success.

PMID- 11966077
TI  - Boys will be men.

PMID- 11966078
TI  - When there's no time to nurse.

PMID- 11966079
TI  - Patient positioning and its effect on brain oxygenation.

PMID- 11966080
TI  - A proactive approach to preventing abuse.

PMID- 11966081
TI  - Critical care outreach teams--a prayer answered?

PMID- 11966082
TI  - How to use medical devices safely.

PMID- 11966083
TI  - Cardiopulmonary resuscitation. Insertion of an oropharyngeal airway.

PMID- 11966084
TI  - A&E services deteriorating steadily.

PMID- 11966085
TI  - NHS down 30,000 young nurses over 10 years.

PMID- 11966086
TI  - Helmets for preventing head and facial injuries in bicyclists.

PMID- 11966087
TI  - A community nurse frustrated because the GPI restricts the range of drugs that
      can be prescribed.

PMID- 11966088
TI  - Midwives could be owed 'thousands' in back-pay.

PMID- 11966089
TI  - NHS needs 'cultural transformation'.

PMID- 11966090
TI  - 'Nurse should not have been fired' says family.

PMID- 11966091
TI  - NHS staff given advice on treating anthrax patients.

PMID- 11966092
TI  - Long-term care. Government may scrap homes.

PMID- 11966093
TI  - Diabetes. National service framework delayed by at least a year.

PMID- 11966094
TI  - Breast cancer. Night shifts put nurses at risk.

PMID- 11966095
TI  - Asthma management. BTS moves to prevent steroid risk to children.

PMID- 11966096
TI  - Cancer care. Call for guidelines on pain relief.

PMID- 11966105
TI  - Winter crisis. That time of year again.

PMID- 11966106
TI  - European health care. Vive la difference?

PMID- 11966107
TI  - Health care assistants. The walls come tumbling down.

PMID- 11966108
TI  - Mental health. Trading places.

PMID- 11966109
TI  - Sepsis occurs in over a quarter of ICU patients.

PMID- 11966111
TI  - Theory and practice in the modern age.

PMID- 11966110
TI  - Will the Afghan people benefit from the west's military action?

PMID- 11966112
TI  - The smokescreen gets in your eyes.

PMID- 11966114
TI  - Safety tips.

PMID- 11966113
TI  - Well-equipped?

PMID- 11966115
TI  - Everyone suffers, but women suffer the most.

PMID- 11966117
TI  - The RCN's call for a review of PFI hospitals is right, if overdue.

PMID- 11966116
TI  - A small price to pay for peace of mind.

PMID- 11966118
TI  - Benchmarking: how do you do it?

PMID- 11966119
TI  - Vaccinating against influenza and pneumococcus.

PMID- 11966120
TI  - Home versus in-patient treatment for deep vein thrombosis.

PMID- 11966121
TI  - Coronary care unit nurses interested in introducing nurse-led thrombolysis.

PMID- 11966122
TI  - Slowing the progression?

PMID- 11966123
TI  - Pain assessment in a day-bed unit.

PMID- 11966124
TI  - RCN call to put PFI on hold.

PMID- 11966125
TI  - Drug error. Inquest spares nurse, but family may still quiz her.

PMID- 11966127
TI  - 3.5m pounds bonus pilot sparks fears of new wage divide.

PMID- 11966126
TI  - Cardiopulmonary resuscitation. Airway management.

PMID- 11966128
TI  - New code of ethics to police rogue agencies.

PMID- 11966129
TI  - Harassment could make students shun placements.

PMID- 11966130
TI  - Red tape is strangling the NHS, claim tories.

PMID- 11966131
TI  - Midwives sacked for bullying.

PMID- 11966132
TI  - Casualties of war.

PMID- 11966133
TI  - Mental health. High time for a change?

PMID- 11966134
TI  - Uncovering the secret journey.

PMID- 11966135
TI  - Should health care assistants be called nurses?

PMID- 11966137
TI  - Nurses can help fight against racist fallout.

PMID- 11966138
TI  - How do I become a school nurse?

PMID- 11966140
TI  - Just do it.

PMID- 11966139
TI  - Taking a stand.

PMID- 11966142
TI  - Postcards from the edge.

PMID- 11966141
TI  - How green was my valley. Interview by David Crouch.

PMID- 11966143
TI  - The who's who of advanced practice.

PMID- 11966145
TI  - Creating a climate of trust.

PMID- 11966144
TI  - Primary care groups and trusts.

PMID- 11966146
TI  - Antidepressant treatment for post-natal depression.

PMID- 11966147
TI  - Most of the women have been circumcised and I am concerned as there are several
      little girls approaching the age of circumcision.

PMID- 11966149
TI  - Coronary heart disease: 2. The assessment, diagnosis and management of stable
      angina.

PMID- 11966148
TI  - How to detect and manage depression in older people.

PMID- 11966151
TI  - Anthrax. When immunity may not be safe.

PMID- 11966152
TI  - Nurse practitioners. What makes an NP?

PMID- 11966153
TI  - Violence in the workplace. It's a crime.

PMID- 11966154
TI  - Mental health. All you need is help.

PMID- 11966155
TI  - Nurse education. How to learn from the locals.

PMID- 11966156
TI  - Is intuition a useful tool for modern nurses?

PMID- 11966157
TI  - Plain talking about nursing.

PMID- 11966158
TI  - The delicate matter of disposal.

PMID- 11966159
TI  - Here's a tip for you--get some proper safety advice.

PMID- 11966160
TI  - Sorted for pills and paperweights.

PMID- 11966161
TI  - Are we breaching confidentiality?

PMID- 11966162
TI  - An uphill struggle.

PMID- 11966163
TI  - Men, monasteries, wars and wards.

PMID- 11966164
TI  - Three of a kind?

PMID- 11966165
TI  - To Scotland's good health.

PMID- 11966166
TI  - Only recruiting more nurses and doctors will rescue A&E services.

PMID- 11966167
TI  - Issues for nurses in dementia diagnosis and management.

PMID- 11966169
TI  - Conflict in court?

PMID- 11966168
TI  - Are nurses receptive to an evidence-based newsletter?

PMID- 11966170
TI  - Supporting nurse returners.

PMID- 11966171
TI  - Coronary heart disease: 1. The disease, anatomy and physiology, and demographics.

PMID- 11966172
TI  - Government acts to end A&E chaos.

PMID- 11966173
TI  - Patient death. Ombudsman orders review of triage times.

PMID- 11966174
TI  - Do diets work?

PMID- 11966175
TI  - Energy, mood and behaviour: Part Two.

PMID- 11966176
TI  - Osteoporosis: prevention and treatment. 1.

PMID- 11966177
TI  - Developing the role of the nurse endoscopist.

PMID- 11966179
TI  - Staff shortages. MPs warn against drain to independent sector.

PMID- 11966178
TI  - Equal opportunities. Half of employers failing to address ethnic mix.

PMID- 11966180
TI  - Welsh health service. Planned shake-up slammed.

PMID- 11966181
TI  - Midwifery. Staffing link to caesarean rate.

PMID- 11966182
TI  - Obstetric interventions. Call to clarify 'normal' birth.

PMID- 11966184
TI  - Nurse prescribing. Burnt-out GPs back extended powers.

PMID- 11966183
TI  - Sudden infant death syndrome. Overheated units putting babies at risk.

PMID- 11966185
TI  - The women's interagency HIV study (WIHS): research findings.

PMID- 11966186
TI  - Stupidity is spelled with a "W".

PMID- 11966187
TI  - Baby, have you come a long way?

PMID- 11966188
TI  - Just the flax, please: Part I.

PMID- 11966189
TI  - Women staying healthly for life.

PMID- 11966190
TI  - Preventive medicine for the new millennium from A to Z.

PMID- 11966191
TI  - The process of drug development.

PMID- 11966192
TI  - Federal budget passes--finally.

PMID- 11966193
TI  - Malone accepts THRIVE! Position.

PMID- 11966194
TI  - Peer counseling perspectives.

PMID- 11966195
TI  - Women and AIDS in Georgia.

PMID- 11966197
TI  - [Sodium ions in the system of electromechanical coupling of the myocardium and
      skeletal muscles of the frog Rana temporaria].

PMID- 11966196
TI  - [Indophenol chromogenic substrates of various cholinesterases].

PMID- 11966198
TI  - [Distribution of activity of major carboxypeptidases in tissues of various
      laboratory animals].

PMID- 11966199
TI  - [Inhibition by various alkaloids of acetylcholinesterase and
      butyrylcholinesterase from human blood].

PMID- 11966200
TI  - [Structure and function of the pineal gland in the vertebrates].

PMID- 11966201
TI  - [Molecular genetics of phenylketonuria in Novosibirsk Region].

PMID- 11966202
TI  - [Heart activity of the crayfish Astacus astacus in various functional states].

PMID- 11966203
TI  - [Mediator sensitivity of primary afferent cells in the spinal cord of the lamprey
      Lamperta fluviatilus].

PMID- 11966204
TI  - [Relationship between the lipid composition of the Anadyr capelin Mallotus
      villosus and its physiological state].

PMID- 11966205
TI  - [The role of calcium ions in the modulation of pulsed activity of the isolated
      muscle spindle in the frog Rana temporaria].

PMID- 11966206
TI  - [Polyunsaturated fatty acids reduce induced pathological changes in rat pups].

PMID- 11966207
TI  - [The effect of timing of weaning from the female on the behavior in open field
      and the state of sympatho-adrenal system in rats growing up in social isolation].

PMID- 11966208
TI  - [Possible role of catalase in the adaptation to diving in semiaquatic rodents
      Ondatra zibethica].

PMID- 11966209
TI  - [Regulating effect of exogenous vasopressin on the autonomic functions and higher
      nervous activity of the hedgehog Erinateus auritus exposed to high temperature of
      the environment].

PMID- 11966210
TI  - [Localization of phosphatase responsible for hydrolysis of inositol-1,4,5
      triphosphate in the olfactory lining of sturgeons].

PMID- 11966211
TI  - [NADPH-diaphorase in the olfactory system of the carp Cyprinus carpio].

PMID- 11966212
TI  - [The role of sulfhydryl groups in the functioning of the adenylate cyclase
      signalling system].

PMID- 11966213
TI  - [The species pool hypothesis: the necessity to shift emphasis].
AB  - The species pool of a biological community is determined as a group of species
      that inhabit some area and potentially can be included in a given community. The
      species pool hypothesis, i.e. the assumption that the size of species pool
      strongly influences species richness of local community can be confirmed if there
      is positive linear relationship between these two variables. The results of
      hypothesis testing however are not obvious. For example, correlation between
      local richness and species pool size can be caused by their dependence on the
      third variable--capacity of environment. It seems that in case of decreasing area
      occupied by local community the environmental conditions become more important
      than species pool size. If that is true, the influence of species pool on local
      species richness is not significant. However one can estimate the degree of
      unsaturation of species pool on the basis of relationships between the number of
      species in small locations occupied by similar local communities and their
      species pool. We think, that study of local and regional species richness should
      shift the emphasis--from the analysis of species pool influence on local
      community richness to the estimation of historical, ecological and anthropogenic
      factors in variation of species pool size. The local species richness should be
      considered rather as a tool (allowing to compare the species capacity of
      biological communities), than as an object of such study.

PMID- 11966214
TI  - [Structure of coadaptive complex of forest entomophylous plants with broad
      spectrum of pollinators].
AB  - Pollinators of common forest entomophylous plants were studied at 1982-1985 near
      Zvenigorod biological station (Moscow region) and at 1989-1993 near Torma (Jogeva
      maakond, Estonia). The comparative analysis of spectra of pollinators has allowed
      to distinguish five groups (subcomplexes) of plants characterized by dominance of
      different groups of pollinators: myiophylous (flies from superfamily Muscoidea
      dominate), syrphidophylous (flies from family Syrphidae dominate), nonspecialized
      melittophylous (Apoidea, mainly bumblebees, dominate), psychophylous (butterflies
      dominate), and cantharophylous (beetles dominate). The belonging of plants to
      concrete subcomplex is determined by the morphology of flowers and
      influorescences, but in some cases habitat and time of blooming are also
      important. From year to year the composition of pollinators of the same plant
      species varies because of change in abundance of different groups of pollinators.
      However for long term these fluctuations are leveled off. External reproductive
      isolation of plants of myiophylous subcomplex is achieved mainly by spatial
      (ecological) and time (different time of flowering) isolations. However when two
      species of the same subcomplex grow together and their flowering time strongly
      overlap, there are some distinction in their pollinators reducing competition for
      pollinators.

PMID- 11966215
TI  - [Explicit model for searching behavior of predator].
AB  - The authors present an approach for explicit modeling of spatio-temporal dynamics
      of predator-prey community. This approach is based on a reaction-diffusion
      adjection PD (prey dependent) system. Local kinetics of population is determined
      by logistic reproduction function of prey, constant natural mortality of predator
      and Holling type 2 trophic function. Searching behavior of predator is described
      by the advective term in predator balance equation assuming the predator
      acceleration to be proportional to the prey density gradient. The model was
      studied with zero-flux boundary conditions. The influence of predator searching
      activity on the community dynamics, in particular, on the emergence of spatial
      heterogeneity, has been investigated by linear analysis and numerical
      simulations. It has been shown how searching activity may effect the persistence
      of species, stabilizing predator-prey interactions at very low level of pest
      density. It has been demonstrated that obtaining of such dynamic regimes does not
      require the use of complex trophic functions.

PMID- 11966216
TI  - Chaos and order in plankton dynamics. Complex behavior of a simple model.
AB  - The role of the diffusive interaction between fish-populated and fish-free
      habitats in a patchy environment in plankton pattern formation is studied by
      means of a minimal reaction-diffusion model of the nutrient-plankton-fish food
      chain. It is shown that such interaction can give rise to spatio-temporal
      plankton patterns. The fractal dimension of the patterns is shown dependent on
      the fish predation rate. The spatially averaged plankton dynamics depending on
      both fish predation rate and distance between fish-populated habitats can exhibit
      chaotic and regular behavior. The chaotic plankton dynamics is characteristic of
      a wide parameter range.

PMID- 11966217
TI  - [Chemical interactions between planktonic crustaceans].
AB  - Three levels of chemical communications involved plankton Crustacea are
      considered: 1) Influence of zooplankton excretion on phytoplankton; 2) Influence
      of zooplankton excretion on the individuals of the same or other species of the
      same trophic level; 3) Influence of chemical cues released by predatory
      zooplankton and fish on herbivorous zooplankton. The data on the influence of
      excreted cues on some physiological (growth, reproduction, feeding, etc.) and
      behavioural (vertical and horizontal migrations) characters of planktonic
      crustaceans are presented. Ecological role and chemistry cues responsible for the
      interactions of different trophic levels can be different. It is considered that
      chemical communications in aquatic ecosystems can be provided with: 1) Species
      specific cues that strictly influence particular biological functions
      (communication system of feromone type); 2) Non-specific cues that strictly
      influence particular functions (system of regulator, that act at the whole
      ecosystem as the hormonal system of an organism). 3) Non-specific substances with
      broad (non-specidic) influence--toxic substances of "biocondition substances"
      according to classification of Novikov and Kharlamova (2000).

PMID- 11966218
TI  - [Revolution in megataxonomy: prerequisites and results].
AB  - Main stages of development of megataxonomy (the science of organic world dividing
      into large taxa) are considered. Prerequisites and first results of "revolution
      in megataxonomy" (cardinal reorganization during last years) are analyzed. Matter
      of "revolution" is considered: changing of main megataxonomic criteria from
      morpho-physiological to cytological and genetical ones. Advantages of
      classifications of organic world based on cytological and genetical criteria, and
      main arguments of their opponents are discussed. Some taxonomic changes based on
      published data are suggested: the kingdom Lamellitubulicristata (lamellicristate
      and tubulicristate eukaryots) is created, Cryptophyta, Prymnesiophyta, Percolozoa
      and Actinozoa are risen up to the kingdom rank. Original megasystem of dominion
      Eukaryota is build up, including 2 subdominions (Hypochondria and Epichondria), 3
      superkingdoms (Hypocrystata, Discocrystata and Lamellitubulicristata) and 14
      kingdoms (Archaeomonadobiontes, Microsporobiontes, Euglenobiontes,
      Percolobiontes, Myxobiontes, Actinobiontes, Alveolobiontes, Chromobiontes,
      Prymnesiobiontes, Cryptobiontes, Rhodobiontes, Chlorobiontes, Mycobiontes and
      Zoobiontes). Characters of these taxa and an outline of their evolutionary
      connections based on published data are provided.

PMID- 11966219
TI  - [IX School on Theoretic Morphology of Plants: "Types of similarity and principles
      of homologation in plant morphology"].

PMID- 11966220
TI  - A fecundity to mortality ratio, population size variability and the chance for a
      mammal species to be listed on the red list.
AB  - How is a species' propensity to vary in size over time related to its chances to
      be listed on the Red List (Red Book), that is to face the risk of extinction?
      Here I suggest that the linkage between the range of population fluctuations and
      chance of listing may be established on the basis of the ratio of species' annual
      fecundity to annual mortality of adults, B/M. For 23 mammalian species inhabiting
      the vast tracts of Western Siberia, the range of population fluctuations is found
      to be equal or at least proportional to B/M. Further, this ratio is estimated for
      a larger set of 90 mammalian species from the territory and coastal waters of the
      former Soviet Union, of which 25 species are listed in the Red Book of the USSR.
      The distribution of the Red Book species over the gradient of B/M is clearly non
      uniform: most of them have low B/M, which leads to a negative relationship
      between chance of listing and B/M. The positive relation between population size
      variability and B/M and the negative relation between chance of listing and B/M
      suggest the resulting negative relation between chance of listing and population
      size variability. Both the positive and the negative relations of, respectively,
      population size variability and chance of listing on B/M are logically justified
      since B/M is a measure of the population growth rate: it is the total lifetime
      offspring and an upper estimate of the growth rate per generation time. Fast
      growing, more resilient species tend to be more resistant to extinction and hence
      to have low chance of listing, but simultaneously are able to fluctuate widely.
      Thus, so long as population growth rate affects both chance of listing and
      population size variability, high variability implies low chance of listing.

PMID- 11966221
TI  - [Use of computer polysomnographic polygraphs in psychophysiology and in clinical
      research].

PMID- 11966222
TI  - [Evaluation of dynamics of immunogram indicators taking into account features of
      clinical status in acute and chronic inflammatory diseases].

PMID- 11966224
TI  - [Influence of visual illusions of features of forming virtual action space].

PMID- 11966223
TI  - [On the problem of neuroimmunologic therapy of nervous system diseases].

PMID- 11966225
TI  - [A safe physiologic challenge test for determining tolerance to dental
      materials].

PMID- 11966226
TI  - [The dominant rule as the basis for cognitive child development at early stages
      on ontogenesis].

PMID- 11966227
TI  - [Spectral characterization of EEG of young school aged children with learning
      disorders].

PMID- 11966228
TI  - [Individual features of functional organization of the brain of children aged 7-8
      with mental retardation in processing visual-spatial information].

PMID- 11966229
TI  - [Physical development and status of psychophysiological functions in young school
      aged children].

PMID- 11966230
TI  - [Age features of the daily dynamics of reaction times to visual stimuli in 8-14
      year old boys].

PMID- 11966232
TI  - [Gravitation and hemispheric specialization of the brain during determination of
      bilateral symmetry].

PMID- 11966231
TI  - [Energy metabolism and spectral characteristics of EEG in students with different
      degrees of neurosis and anxiety in exam stress situations].

PMID- 11966234
TI  - [Duration of voluntary breath holding and blood parameters].

PMID- 11966233
TI  - [Specific characteristics of healthy volunteers with various reactions to
      emotional stress].

PMID- 11966235
TI  - [Analysis of variability of cardiac rhythm in space medicine].

PMID- 11966236
TI  - [Age-related erythrocyte structure and rheological properties of blood in
      athletes].

PMID- 11966237
TI  - [Hemodynamic reactions in static and dynamic physical loads in athletes].

PMID- 11966238
TI  - [Studies of dysmetabolic neuropathies with uratemia in children in an arid region
      of Turkmenistan].

PMID- 11966240
TI  - Editorial comment: the increasing problem of HIV-associated nephropathy.

PMID- 11966239
TI  - Resolution of renal failure after initiation of HAART: 3 cases and a discussion
      of the literature.
AB  - Renal failure is a known complication of HIV infection. The most common form is
      HIV-associated nephropathy, or HIVAN. It is characterized by high-grade
      proteinuria with rapid progression to end-stage renal disease. The kidneys of
      affected patients appear enlarged on ultrasonography. Histopathologically, there
      is focal segmental glomerulosclerosis with glomerular collapse. Before the era of
      HAART, patients with HIVAN had limited survival, although in some cases this was
      prolonged if dialysis was instituted. Over the past few years, isolated case
      reports have shown that patients with HIVAN will recover renal function following
      initiation of HAART. We report 3 patients believed to have HIVAN who exhibited
      marked improvement in renal function after treatment with a regimen comprising 2
      nucleoside reverse transcriptase inhibitors and a protease inhibitor.

PMID- 11966241
TI  - Identifying and managing morphologic complications of HIV and HAART.
AB  - Morphologic complications continue to be observed in patients receiving HAART.
      Body habitus changes include fat accumulation, lipoatrophy, and HIV-associated
      wasting. Anthropometry, dual-energy x-ray absorptiometry, and imaging methods
      (CT, MRI) are most useful for detecting fat redistribution syndromes, while
      bioelectric impedance analysis is useful for determining and monitoring wasting.
      Various clinical interventions, including diet and exercise, switching
      antiretroviral agents, the use of lipid-lowering and insulin-sensitizing agents,
      recombinant human growth hormone therapy, and plastic surgery, are under
      investigation for the treatment of morphologic changes. Prospective, controlled
      clinical trials are needed to determine the long-term efficacy of these
      approaches.

PMID- 11966242
TI  - "Scientific gambles": AIDS microbicides and vaccines.

PMID- 11966243
TI  - Efficacy and safety of once-daily antiretroviral therapy.

PMID- 11966244
TI  - A 14-month-old boy with an apparent life-threatening event.

PMID- 11966245
TI  - The history of the pneumococcus.

PMID- 11966246
TI  - Pneumococcal microbiology and immunity.

PMID- 11966247
TI  - Pneumococcal infections in children.

PMID- 11966248
TI  - Mechanisms of pneumococcal antibiotic resistance and treatment of pneumococcal
      infections in 2002.

PMID- 11966249
TI  - Pneumococcal vaccines: present and future.

PMID- 11966250
TI  - On the road to recovery.

PMID- 11966251
TI  - Married white female.

PMID- 11966252
TI  - The missing link.

PMID- 11966253
TI  - Mental health. Let's get physical.

PMID- 11966254
TI  - Should nurses decide which care home residents get free care?

PMID- 11966256
TI  - A ballerina-length gown made all the difference.

PMID- 11966257
TI  - R. E. S. P. E. C. T. Protecting the privacy and dignity of patients is a long
      standing staple of nursing.

PMID- 11966259
TI  - Who will train the inspectors?

PMID- 11966258
TI  - She's heard it all before. Interview by Adam James.

PMID- 11966260
TI  - Benign breast disease.

PMID- 11966261
TI  - We can work it out.

PMID- 11966262
TI  - Alarm interventions for nocturnal enuresis in children.

PMID- 11966263
TI  - I am setting up a smoking cessation service for inpatients in an acute trust. How
      is smoking status assessed on admission and how are patients referred to other
      cessation services?

PMID- 11966264
TI  - Moving on up: a higher level of practice.

PMID- 11966270
TI  - Care of the elderly. The heat is on.

PMID- 11966266
TI  - The hepatitis viruses. 1. Transmission, signs, symptoms and diagnosis.

PMID- 11966271
TI  - Infection control. Now wash your hands.

PMID- 11966272
TI  - HIV/AIDS. World inaction.

PMID- 11966273
TI  - Nurse prescribing. A spoonful of sugar.

PMID- 11966275
TI  - Not too late to regulate.

PMID- 11966274
TI  - Should nurses always intervene when patients self-harm?

PMID- 11966276
TI  - Is elderly care a waste of your training?

PMID- 11966277
TI  - Is elderly care a waste of your training?

PMID- 11966278
TI  - Researching the art of nursing.

PMID- 11966279
TI  - Strict patient routines can be abusive.

PMID- 11966280
TI  - Winning combination.

PMID- 11966281
TI  - Whistleblowing. Caught between a rock and a hard place.

PMID- 11966282
TI  - Click here for e-learning.

PMID- 11966283
TI  - Nurse education needs a lifeline.

PMID- 11966284
TI  - After Bristol: the importance of informed consent.

PMID- 11966285
TI  - Psychotherapy with a soul.

PMID- 11966286
TI  - Acting on dilemmas in palliative care.

PMID- 11966288
TI  - Oncology. Community nurses lack colleagues' support.

PMID- 11966287
TI  - The hepatitis viruses. Rationales for treatment, occupation health issues and
      current guidelines for best practice.
AB  - Nurses are likely to come across any one, or all, of the hepatitis viruses A, B,
      C, D, E, (F) and G at some point in their career. It is important, therefore,
      that they are familiar with basic details concerning the viruses, such as their
      mode of transmission, methods of diagnosis and the prognosis for those who are
      infected. It is also important that they are aware of the implications for the
      health of individuals and the communities in which they live. Hepatitis B virus
      remains a global problem, with 5% of the world's population chronically infected.
      HCV is not that far behind, with 3% of the world's population infected, although
      the numbers are rising. HAV and HEV are less of an issue in both the developing
      and developed worlds and are relatively self-limiting as disease entities. Nurses
      play an important role in prevention and care services for both acute and chronic
      hepatitis. Whether they are providing needle exchanges, or involved in monitoring
      complex treatment programmes, their input is invaluable. Of equal importance is
      the involvement of patient groups and non-government organisations that have done
      much in the way of raising awareness and lobbying for funding for services and
      treatments. If nurses can respond appropriately and sensitively to the known
      hepatitis viruses, they will be well prepared to deal with those infections that
      have still to be discovered.

PMID- 11966289
TI  - Careers focus. Tomorrow's world.

PMID- 11966290
TI  - Infection control. Staff to be screened for risk they pose to patients.

PMID- 11966291
TI  - Scotland. Job cuts are 'absolute madness'.

PMID- 11966293
TI  - Adolescent health. Call for sexual health services in schools.

PMID- 11966292
TI  - 500 extra nurses to ease winter pressures.

PMID- 11966294
TI  - Whistleblowing. Nurse awarded damages for wrongful discipline.

PMID- 11966295
TI  - Education. Strategy for lifelong learning.

PMID- 11966296
TI  - NHS funding. More nurses won't mean better care, says report.

PMID- 11966297
TI  - Education. Demand for clinical teachers on wards.

PMID- 11966299
TI  - Professional development. Nurses dominate leadership course.

PMID- 11966298
TI  - Infection control. Call for annual hand hygiene audit.

PMID- 11966300
TI  - Breast cancer. UK nurses are key source of information.

PMID- 11966301
TI  - Plume dynamics and shielding by the ablation plume during Er:YAG laser ablation.
AB  - Free-running Er:YAG lasers are used for precise tissue ablation in various
      clinical applications. The ablated material is ejected into the direction
      perpendicular to the tissue surface. We investigated the influence of shielding
      by the ablation plume on the energy deposition into an irradiated sample because
      it influences the ablation dynamics and the amount of material ablated. The
      investigations were performed using an Er:YAG laser with a pulse duration of 200
      micros for the ablation of gelatin with different water contents, skin, and
      water. Laser flash photography combined with a dark field Schlieren technique was
      used to visualize gaseous and particulate ablation products, and to measure the
      distance traveled by the ablating laser beam through the ablation plume at
      various times after the beginning of the laser pulse. The temporal evolution of
      the transmission through the ablation plume was probed using a second free
      running Er:YAG laser beam directed parallel to the sample's surface. The ablation
      dynamics was found to consist of a vaporization phase followed by material
      ejection. The observation of droplet ejection during water ablation provided
      evidence that a phase explosion is the driving mechanism for material ejection.
      The laser light transmission was only slightly reduced by the vapor plume, but
      decreased by 25%-50% when the ejected material passed the probe beam. At radiant
      exposures approximately 10 times above the ablation threshold, the laser energy
      deposited into the sample amounted to only 61% of the incident energy for gelatin
      samples with 90% water content and to 86% for skin samples. For free-running
      Er:YAG laser pulses shielding must therefore be considered in modeling the
      ablation dynamics and determining the dosage for clinical applications.

PMID- 11966302
TI  - Computer-assisted laser photocoagulation of the retina--a hybrid tracking
      approach.
AB  - A system for robotically assisted retinal surgery has been developed to rapidly
      and safely place lesions on the retina for photocoagulation therapy. This system
      provides real-time, motion stabilized lesion placement for typical irradiation
      times of 100 ms. The system consists of three main subsystems: a digital-based
      global tracking subsystem; a fast, analog local tracking subsystem; and a
      confocal reflectance subsystem to control lesion parameters dynamically. We have
      reported previously on these individual subsystems. This paper concentrates on
      the development of a second hybrid system prototype. Considerable progress has
      been made toward reducing the footprint of the optical system, simplifying the
      user interface, fully characterizing the analog tracking system, using measurable
      lesion reflectance parameters to develop a noninvasive method to infer lesion
      depth, and integrating the subsystems into a seamless hybrid system. These system
      improvements and progress toward a clinically significant system are covered in
      detail within this paper. The tracking algorithms and concepts developed for this
      project have considerable potential for application in many other areas of
      biomedical engineering.

PMID- 11966303
TI  - Comparison of fluorescence of sodium fluorescein in retinal angiography with
      measurements in vitro.
AB  - To quantify dye leakage in ocular fluorescein angiography, the arterial
      concentration of sodium fluorescein has to be determined. We investigated whether
      the nonlinear relationship between the fluorescein concentration and the
      fluorescence intensity obtained by in vitro measurements corresponds with that
      measured in vivo in a retinal artery. The time series of fluorescence in a
      retinal artery were recorded using an in-house-designed and -built confocal
      scanning laser ophthalmoscope in 11 healthy volunteers. Three different doses of
      sodium fluorescein were injected successively. About 10 min after the last
      injection a venous blood sample was drawn. The three in vivo peak intensities
      were fitted by least squares on the in vitro calibration curve using the first
      peak concentration and an intensity scaling factor as the two unknown parameters.
      The fit showed that the saturation of the three in vivo peak intensities
      corresponded well with the in vitro data. Calculation of the intensity scaling
      factor from the blood sampling data confirmed the result of the fit. The fitted
      concentration was verified by showing that the cardiac output necessary to obtain
      this concentration was within the physiological range. The fluorescence measured
      in our in vitro experimental setup corresponded well with the in vivo
      measurements. Therefore, the results from in vitro measurements can be applied in
      the analysis of fluorescein angiograms.

PMID- 11966304
TI  - Linear birefringence of the retinal nerve fiber layer measured in vitro with a
      multispectral imaging micropolarimeter.
AB  - Scanning laser polarimetry (SLP) assesses the retinal nerve fiber layer (RNFL)
      for glaucoma diagnosis by detecting the birefringence of the peripapillary RNFL.
      A detailed understanding of SLP requires an accurate value for RNFL birefringence
      in order to relate measured retardance to RNFL thickness, but current knowledge
      of this value is limited. A multispectral imaging micropolarimeter of PSC'A type
      was used to measure the retardance in transmission of the RNFL of isolated rat
      retina before (living) and after (fixed) 20 min of glutaraldehyde fixation. The
      thickness of the nerve fiber bundles measured was then determined histologically.
      As previously known from reflectance measurements, in transmission the RNFL
      behaved as a linear retarder. The retardance of the RNFL was constant at
      wavelengths from 440 to 830 nm and persisted after tissue fixation. In 37 nerve
      fiber bundles of 8 retinas, the average RNFL birefringence was 0.23 nm/microm
      before and 0.19 nm/microm after fixation, with an uncertainty of 0.01 nm/microm.
      The wavelength independence is consistent with a mechanism of form birefringence
      from thin cylindrical organelles. These results allow extrapolation of previous
      visible wavelength measurements to the near-infrared wavelengths used by SLP and
      validate the use of fixed tissue for RNFL research.

PMID- 11966305
TI  - Polarization-dependent optical second-harmonic imaging of a rat-tail tendon.
AB  - Using scanning confocal microscopy, we measure the backscattered second harmonic
      signal generated by a 100 fs laser in rat-tail tendon collagen. Damage to the
      sample is avoided by using a continuous scanning technique, rather than measuring
      the signal at discrete points. The second harmonic signal varies by about a
      factor of 2 across a single cross section of the rat-tail tendon fascicle. The
      signal intensity depends both on the collagen organization and the backscattering
      efficiency. This implies that we cannot use intensity measurements alone to
      characterize collagen structure. However, we can infer structural information
      from the polarization dependence of the second harmonic signal. Axial and
      transverse scans for different linear polarization angles of the input beam show
      that second harmonic generation (SHG) in the rat-tail tendon depends strongly on
      the polarization of the input laser beam. We develop an analytical model for the
      SHG as a function of the polarization angle in the rat-tail tendon. We apply this
      model in determining the orientation of collagen fibrils in the fascicle and the
      ratio gamma between the two independent elements of the second-order nonlinear
      susceptibility tensor. There is a good fit between our model and the measured
      data.

PMID- 11966306
TI  - Localization and staging of cervical intraepithelial neoplasia using double ratio
      fluorescence imaging.
AB  - A phase zero evaluation of a new fluorescence imaging technique for diagnosing
      cervical intraepithelial neoplasia (CIN) was performed. The fluorescence imaging
      prototype performed quantitative imaging of Protoporphyrin induced by a topically
      applied aminolevulinic acid using double ratio (DR) fluorescence imaging
      technique developed by our group. A total of 38 patients were in the protocol,
      with 16 colposcopically selected for biopsy. Fluorescence images of these 16
      patients were taken, 19 sites were biopsied, and the disease was staged
      histopathologically. DR fluorescence imaging of the cervix using our general
      purpose prototype appeared to be cumbersome but feasible. In four cases strongly
      localized fluorescent hotspots were observed at the location where the disease
      was colposcopically visible. In the other cases the fluorescence showed a more
      diffuse multifocal image. The value of the DR determined at the site of biopsy
      correlated in a statistically significant way with the histopathologically
      determined stage of the disease [Spearman rank correlation, r=0.881, p<0.001
      (confidence interval 0.7044-0.9552)]. This suggests that noninvasive staging of
      CIN using this technique is feasible. We believe that the results of this study
      justify the development of a dedicated device that combines regular white light
      colposcopy with DR fluorescence imaging.

PMID- 11966307
TI  - Comparison of three methods to measure absolute cerebral hemoglobin concentration
      in neonates by near-infrared spectrophotometry.
AB  - Three methods by which to determine absolute total cerebral hemoglobin
      concentration (tHb in micromol/L) by near-infrared spectrophotometry (NIRS) have
      evolved: (1) tHbo, requiring oxygenation changes and arterial oxygen saturation
      measurements as a reference using a relative NIRS algorithm, (2) tHbg, using a
      geometrical multidistance principle and (3) tHbgo, a combination of both. The aim
      of this study was to compare the three methods quantitatively. Sixteen clinically
      stable preterm infants with a mean gestational age of 29.6 (range of 25.1-36.4)
      weeks, birthweight of 1386 (680-2820) g and a postnatal age of 2.5 (0.5-6) days,
      who needed supplemental oxygen, were enrolled. The mean+/-standard deviation tHbg
      was 150.2+/-41.8 micromol/L (range of 61.6-228.9 micromol/L), the tHbo was 62.1+/
      27.2 micromol/L (26.0-110.8 micromol/L) and the tHbgo was 89.3+/-45.6 micromol/L
      (26.5-195.9 micromol/L). The correlation coefficient among the three methods were
      tHbg and tHbgo r=0.736; tHbo and tHbgo r=0.938; tHbg and tHbo r=0.598. A multiple
      regression with variable selection by Mellow's C(p) showed, that tHbg was
      correlated to the birthweight, the postnatal age, the heart rate and the pCO2
      (r(2)=0.588), tHbo and tHbgo were associated with the hemoglobin concentration in
      the blood, the mean arterial blood pressure and the pCO2 (r(2)=0.493 and 0.406,
      respectively). The three methods (tHbg, tHbo, and tHbgo) give systematically
      different tHb readings and large intersubject variability.

PMID- 11966308
TI  - Continuous-wave near-infrared spectroscopy using pathlength-independent hypoxia
      normalization.
AB  - A general physiological model for the hemodynamic response during altered blood
      flow, oxygenation, and metabolism is presented. Calculations of oxy-, deoxy-, and
      total hemoglobin changes during stimulation are given. It is shown that by using
      a global hyperoxic or mild hypoxic challenge it is possible to normalize the
      activation response in terms of the fractional changes in the cerebral blood
      volume, tissue oxygenation index, and oxygen extraction ratio, which are
      independent of the optical pathlength. Using a dual wavelength spectrometer, the
      method is validated by measuring pathlength-independent hemodynamic responses
      during mild hypercarbia in a rat model. Phantom experiments showed that the
      changes in optical pathlength were small as the hemoglobin concentration was
      varied over a wide range. The determination of quantitative parameters
      facilitates the use of continuous-wave transcranial methods by providing a means
      by which to characterize activation response across subjects.

PMID- 11966309
TI  - Influence of optical properties and fiber separation on laser doppler flowmetry.
AB  - Microcirculatory blood flow can be measured using a laser Doppler flowmetry (LDF)
      probe. However, the readings are affected by the tissue's optical properties
      (absorption and scattering coefficients, mu(a) and mu(s)) and probe geometry. In
      this study the influence of optical properties [mu(a)in(0.053,0.23) mm
      1,mu(s)in(14.7,45.7) mm-1] on LDF perfusion and LDF sampling depth was evaluated
      for different fiber separations. In vitro measurements were made on a
      sophisticated tissue phantom with known optical properties that mimicked blood
      flow at different depths. Monte Carlo simulations were carried out to extend the
      geometry of the tissue phantom. A good correlation between measured and simulated
      data was found. The simulations showed that, for fixed flow at a discrete depth,
      the influence of mu(s) or mu(a) on LDF perfusion increased with an increase in
      flow depth and decreased with an increase in fiber separation. For a homogeneous
      flow distribution, however, the perfusion varied 40% due to variations in the
      optical properties, almost independent of the fiber separation (0.23-1.61 mm).
      Therefore, the effect in real tissue is likely to vary due to the unknown
      heterogeneous blood flow distribution. Further, the LDF sampling depth increased
      with a decrease in mu(s) or mu(a) and an increase in fiber separation. For fiber
      separation of 0.46 mm, the e-1 sampling depth ranged from 0.21 to 0.39 mm.

PMID- 11966310
TI  - Properties of erythrocyte light refraction in diabetic patients.
AB  - Since hyperglycaemia changes the erythrocyte cell membrane fluidity and impairs
      cell deformity, our goal was to characterize hemoglobin and red blood cell (RBC)
      light refractive property changes in diabetic patients. Microscopic investigation
      was carried out on intact and fixed RBCs. To determine the refractive index (RI):
      smears of peripheral blood were air dried and fixed for 3 min in methanol.
      Mixtures of polyvinylpyrolidine and buffer of different pH (1:1) were used as
      embedding media. Intact RBCs were mixed with a buffered embedding medium, placed
      on a slide and overlaid with a coverslip. Interference microscopy was used for RI
      measurements at 18 different pH (pH=2-13). The results showed that curves of the
      RI of diabetic patients and of a control group were of similar configuration,
      with one branch in the acidic portion of the pH scale, a maximum and two minima
      in the neutral (middle) portion, and one branch in the alkaline portion. The
      curves of the individuals from the control group overlapped each other. To the
      contrary, the curves of the diabetic patients were not uniform in the neutral
      portion and the alkaline portion. The curves of the diabetic patients in the
      neutral zone were shifted towards the alkaline end of the pH scale, and the RBC
      RI curves were lower in comparison to the control curves. The center maximum of
      the curves of diabetic patients corresponded to pH=6.6 whereas the central
      maximum of the control group curves was at pH=6.2-6.8. Contrary to in the
      diabetic group, intact RBC RI curves in the control group revealed only one
      significantly different minimum at pH of 7.2 in the neutral zone. Using this
      method it is possible to show phenotypic differences between uniform type intact
      and fixed cells, erythrocytes of diabetic patients and of healthy donors.

PMID- 11966311
TI  - Diagnostic potential of Fourier-transform infrared microspectroscopy and advanced
      computational methods in colon cancer patients.
AB  - Colon cancer is the third leading class of cancer causing increased mortality in
      developed countries. A polyp is one type of lesion observed in a majority of
      colon cancer patients. Here, we report a microscopic Fourier transform infrared
      (FTIR) study of normal, adenomatous polyp and malignant cells from biopsies of 24
      patients. The goal of our study was to differentiate an adenomatous polyp from a
      malignant cell using FTIR microspectroscopy and artificial neural network (ANN)
      analysis. FTIR spectra and biological markers such as phosphate, RNA/DNA derived
      from spectra, were useful in identifying normal cells from abnormal ones that
      consisted of adenomatous polyp and malignant cells. However, the biological
      markers failed to differentiate between adenomatous polyp and malignant cases. By
      employing a combination of wavelet features and an ANN based classifier, we were
      able to classify the different cells as normal, adenomatous polyp and cancerous
      in a given tissue sample. The percentage of success of classification was 89%,
      81%, and 83% for normal, adenomatous polyp, and malignant cells, respectively. A
      comparison of the method proposed with the pathological method is also discussed.

PMID- 11966312
TI  - Comparison of analog and digital Fourier transforms in medical image analysis.
AB  - The effectiveness and limitations of medical image processing using analog and
      digital methods are studied. Several types of errors introduced during the image
      processing are analyzed. For the analog optical Fourier transform, errors are
      introduced by the vignetting effect and lens aberration. For the digital Fourier
      transform, errors are introduced by the aliasing effect and the band limit. To
      compare the results obtained by the two techniques, a set of x-ray images was
      processed both optically and digitally. The former was achieved by an optical
      system containing a large Fourier telephoto lens and the latter by a personal
      computer using a Fourier transform algorithm. The veracity of both the optical
      and digital Fourier spectra is analyzed. Our results indicate that the optical
      method has high speed due to parallel processing. High veracity can be achieved
      in high frequency regions by using an optimal optical system. In comparison, the
      digital method has the advantages of high processing precision and
      programmability, but has low processing speed. The comparison of the two
      different techniques presented in this article can provide a basis for selection
      of the processing method in different clinical settings. Even with today's fast
      computers, the optical method is still suitable for many clinical applications.
      The best choice lies in an analog-digital combination.

PMID- 11966313
TI  - Photomechanical investigations on post endodontically rehabilitated teeth.
AB  - An investigation of the stress distribution patterns in post-core restored teeth
      and the behavior of dentin material to fracture propagation was conducted using
      experimental techniques such as digital photoelasticity (on photoelastic models),
      mechanical testing and scanning electron microscopy (SEM) (on extracted teeth).
      Digital photoelastic experiments showed that endodontic post-core restoration
      resulted in regions of high tensile stress and of stress concentrations in the
      remaining dentin structure. It was observed from mechanical testing that the
      fracture resistance in post-core restored teeth is significantly lower (p<0.0001)
      than that in intact tooth. There was a significant correspondence between the
      plane of stress concentrations identified in the photoelastic models and in those
      of the plane of fracture exhibited by the rehabilitated tooth specimens. While
      the fracture of post-core rehabilitated teeth was consistent, that of control
      teeth was not as distinct. The SEM highlighted varying dentin response to
      fracture propagation at the inner core and the outer regions. The fractographs
      showed brittle and ductile response to fracture propagation in the outer and
      inner core dentin, respectively. These photomechanical studies highlighted that
      the stress concentrations, high tensile stress and loss of inner ductile dentin
      associated with post endodontic rehabilitation diminished their resistance to
      fracture.

PMID- 11966314
TI  - Uneven distributions of naive and memory T cells in the CD4 and CD8 T-cell
      populations derived from a single stem cell in an atomic bomb survivor:
      implications for the origins of the memory T-cell pools in adulthood.
AB  - The processes that lead to the establishment and maintenance of memory T-cell
      pools in humans are not well understood. In this study, we examined the emergence
      of naive and memory T cells in an adult male who was exposed to an atomic bomb
      radiation dose of approximately 2 Gy in 1945 at the age of 17. The analysis
      presented here was made possible by our earlier observation that this particular
      individual carries a hematopoietic stem cell mutation at the hypoxanthine
      phosphoribosyltransferase (HPRT) locus that is almost certainly a result of his
      exposure to A-bomb radiation. Our key finding is that we detected a very much
      higher HPRT mutant frequency in the naive (CD45RA(+)) cell component of this
      individual's CD4 and CD8 T-cell populations than in the memory (CD45RA(-)) cell
      component of his CD4 and CD8 T-cell populations. This stands in marked contrast
      to our finding that HPRT mutant frequencies are fairly similar in the naive
      CD45RA(+) and memory CD45RA(-) components of the CD4 and CD8 T-cell populations
      of three unexposed individuals examined concurrently. In addition we found that
      the HPRT mutant frequencies were about 30-fold higher in the naive (CD45RA(+))
      CD4 T cells of the exposed individual than in his memory (CD45RA(-)) cell
      populations, but that the effect was a little less striking in his CD8 cell
      populations, where the HPRT mutant frequencies were only about 15-fold higher in
      his naive T-cell pools than in his memory T-cell pools. We further found that
      100% of the HPRT mutant cells in both his CD4 and CD8 naive cell subsets appeared
      to have originated from repeated divisions of the initial HPRT mutant stem cell,
      whereas only 4 of 24 and 5 of 6 mutant cells in his CD4 and CD8 memory cell
      subsets appeared to have originated from that same stem cell. The most
      straightforward conclusion may be that the great majority of the T cells produced
      by this individual since he was 17 years old have remained as naive-type T cells,
      rather than having become memory-type T cells. Thus the T cells that have been
      produced from the hematopoietic stem cells of this particular A-bomb-exposed
      individual seldom seem to enter and/or to remain in the memory T-cell pool for
      long periods. We speculate that this constraint on entry into memory T-cell pools
      may also apply to unirradiated individuals, but in the absence of genetic markers
      to assist us in obtaining evidential support, we must await clarifying
      information from radically different experimental approaches.

PMID- 11966315
TI  - Noninvasive detection of radiation-induced optic neuropathy by manganese-enhanced
      MRI.
AB  - Available imaging techniques have a limited ability to detect radiation-induced
      injury of the normal brain. In particular, there is no noninvasive method
      available for detection of structural or functional neuronal damage induced by
      radiation. This study was designed to determine whether MRI enhanced using the
      neuronal track tracer MnCl(2) can detect radiation-induced optic neuropathy. A
      single dose of radiation (35 Gy) was delivered to produce optic neuropathy in
      Fischer 344 rats by using a stereotactic method with a 6-mm dorsoventral
      secondary collimator. At 6 months after irradiation, MRI was performed in 1-mm
      sections using a 7-T magnetic field with the neuronal tracer MnCl(2) injected
      into the vitreous of the eye 24 h prior to imaging. The rats were then killed
      humanely for a histological study with hematoxylin and eosin, glial fibrillary
      acidic protein (Gfap) for the detection of astrocytic activity, Luxol Fast
      Blue/Periodic Acid Schiff (LFB/PAS) for the detection of myelinization status,
      and Bielschowski silver stain for axon status. In nonirradiated control animals,
      T1-weighted MRI with manganese vitreous injection revealed an optic nerve track
      that was brightly enhanced from the orbit to the optic chiasm. In the irradiated
      animals, there was clear evidence of the damage at the optic chiasm and optic
      nerves, with loss of axon and demyelinization within the site of irradiation upon
      histological examination. T1-weighted MRI with manganese vitreous injection
      showed an enhancing optic nerve posterior to the orbit. However, this enhancement
      disappeared at the site of irradiation. The area of loss of manganese contrast on
      the MRI scan correlated well with the area of histological abnormality showing
      axonal degeneration and demyelinization. Radiation-induced optic neuropathy was
      thus detected noninvasively by MRI with the antegrade neuronal tracer manganese,
      which exhibited negative contrast enhancement by causing loss of signal. This
      study represents the first demonstration of MR imaging of radiation-induced
      neuronal damage and could provide a means to explore the biological and
      functional integrity of neuronal pathways.

PMID- 11966316
TI  - The effect of 835.62 MHz FDMA or 847.74 MHz CDMA modulated radiofrequency
      radiation on the induction of micronuclei in C3H 10T(1/2) cells.
AB  - To determine if radiofrequency (RF) radiation induces the formation of
      micronuclei, C3H 10T(1/2) cells were exposed to 835.62 MHz frequency division
      multiple access (FDMA) or 847.74 MHz code division multiple access (CDMA)
      modulated RF radiation. After the exposure to RF radiation, the micronucleus
      assay was performed by the cytokinesis block method using cytochalasin B
      treatment. The micronuclei appearing after mitosis were scored in binucleated
      cells using acridine orange staining. The frequency of micronuclei was scored
      both as the percentage of binucleated cells with micronuclei and as the number of
      micronuclei per 100 binucleated cells. Treatment of cells with cytochalasin B at
      a concentration of 2 microg/ml for 22 h was found to yield the maximum number of
      binucleated cells in C3H 10T(1/2) cells. The method used for the micronucleus
      assay in the present study detected a highly significant dose response for both
      indices of micronucleus production in the dose range of 0.1-1.2 Gy and it was
      sensitive enough to detect a significant (P > 0.05) increase in micronuclei after
      doses of 0.3 Gy in exponentially growing cells and after 0.9 Gy in plateau-phase
      cells. Exponentially growing cells or plateau-phase cells were exposed to CDMA
      (3.2 or 4.8 W/kg) or FDMA (3.2 or 5.1 W/kg) RF radiation for 3, 8, 16 or 24 h. In
      three repeat experiments, no exposure condition was found by analysis of variance
      to result in a significant increase relative to sham-exposed cells either in the
      percentage of binucleated cells with micronuclei or in the number of micronuclei
      per 100 binucleated cells. In this study, data from cells exposed to different RF
      signals at two SARs were compared to a common sham-exposed sample. We used the
      Dunnett's test, which is specifically designed for this purpose, and found no
      significant exposure-related differences for either plateau-phase cells or
      exponentially growing cells. Thus the results of this study are not consistent
      with the possibility that these RF radiations induce micronuclei.

PMID- 11966317
TI  - Low-dose radiation hypersensitivity in human tumor cell lines: effects of cell
      cell contact and nutritional deprivation.
AB  - The hyper-radiosensitivity at low doses recently observed in vitro in a number of
      cell lines is thought to have important implications for improving tumor
      radiotherapy. However, cell-cell contact and the cellular environment influence
      cellular radiosensitivity at higher doses, and they may alter hyper
      radiosensitivity in vivo. To confirm this supposition, we investigated the
      effects of cell density, multiplicity and nutritional deprivation on low-dose
      hypersensitivity in vitro. Cell survival in the low-dose range (3 cGy to 2 Gy)
      was studied in cells of two human glioma (BMG-1 and U-87) and two human oral
      squamous carcinoma (PECA-4451 and PECA-4197) lines using a conventional
      macrocolony assay. The effects of cell density, multiplicity and nutritional
      deprivation on hyper-radiosensitivity/induced radioresistance were studied in
      cells of the BMG-1 cell line, which showed prominent hypersensitivity and induced
      radioresistance. The induction of growth inhibition, cell cycle delay,
      micronuclei and apoptosis was also studied at the hyper-radiosensitivity-inducing
      low doses. Hyper-radiosensitivity/induced radioresistance was evident in the
      cells of all four cell lines to varying extents, with maximum sensitivity at 10
      30 cGy, followed by an increase in survival up to 50 cGy-1 Gy. Both the glioma
      cell lines had more prominent hyper-radiosensitivity than the two squamous
      carcinoma cell lines. Low doses inducing maximum hyper-radiosensitivity did not
      cause significant growth inhibition, micronucleation or apoptosis in BMG-1 cells,
      but a transient G(1)/S-phase block was evident. Irradiating and incubating BMG-1
      cells at high density for 0 or 4 h before plating, as well as irradiating cells
      as microcolonies, reduced hyper-radiosensitivity significantly, indicating the
      role of cell-cell contact-mediated processes. Liquid holding of BMG-1 cells in
      HBSS + 1% serum during and after irradiation for 4 h significantly reduced hyper
      radiosensitivity, suggesting that hyper-radiosensitivity may be due partly to
      active damage fixation processes at low doses. Therefore, our findings suggest
      that the damage-induced signaling mechanisms influenced by (or mediated through)
      cell-cell contact or the cellular environment, as well as the lesion fixation
      processes, play an important role in hyper-radiosensitivity. Further studies are
      required to determine the exact nature of the damage that triggers these
      responses as well as for evaluating the potential of low-dose therapy.

PMID- 11966318
TI  - Relationship between radiation-induced low-dose hypersensitivity and the
      bystander effect.
AB  - Recent advances in our knowledge of the biological effects of low doses of
      ionizing radiation have shown two unexpected phenomena: a "bystander effect" that
      can be demonstrated at low doses as a transferable factor(s) causing
      radiobiological effects in unexposed cells, and low-dose hyper-radiosensitivity
      and increased radioresistance that can be demonstrated collectively as a change
      in the dose-effect relationship, occurring around 0.5-1 Gy of low-LET radiation.
      In both cases, the effect of very low doses is greater than would be predicted by
      conventional DNA strand break/repair-based radiobiology. This paper addresses the
      question of whether the two phenomena have similar or exclusive mechanisms. Cells
      of 13 cell lines were tested using established protocols for expression of both
      hyper-radiosensitivity/increased radioresistance and a bystander response. Both
      were measured using clonogenicity as an end point. The results showed
      considerable variation in the expression of both phenomena and suggested that
      cell lines with a large bystander effect do not show hyper-radiosensitivity. The
      reverse was also true. This inverse relationship was not clearly related to the
      TP53 status or malignancy of the cell line. There was an indication that cell
      lines that have a radiation dose-response curve with a wide shoulder show hyper
      radiosensitivity/increased radioresistance and no bystander effect. The results
      may suggest new approaches to understanding the factors that control cell death
      or the sectoring of survival at low radiation doses.

PMID- 11966319
TI  - Detection of genetic alterations induced by low-dose X rays: analysis of loss of
      heterozygosity for TK mutation in human lymphoblastoid cells.
AB  - To elucidate the genetic influence of low-dose ionizing radiation at the
      chromosome level, we exposed human lymphoblastoid TK6-20C cells to 10 cGy of X
      rays. The TK mutation frequency was 5.7 +/- 1.3 x 10(-6) at the background level
      and 6.9 +/- 2.8 x 10(-6) after X irradiation. Although this small increase was
      not statistically significant (P = 0.40), we applied multilocus analysis using 4
      TK locus markers and 12 microsatellite loci spanning chromosome 17 for TK mutants
      exhibiting loss of heterozygosity (LOH). The analysis demonstrated a clear effect
      of low-dose ionizing radiation. We observed radiation-specific patterns in the
      extent of hemizygous LOH in 14 TK mutants among the 92 mutants analyzed. The
      deleted regions in these patterns were larger than they were in the control
      mutants, where those restricted to the TK locus. Surprisingly, the radiation
      specific LOH patterns were not observed among the 110 nonirradiated TK mutants in
      this study. They were identified previously in TK6 cells exposed to 2 Gy of X
      rays. We consider these hemizygous LOH mutants to be a result of end-joining
      repair of X-ray-induced DNA double-strand breaks.

PMID- 11966320
TI  - The cellular lethality of radiation-induced chromosome translocations in human
      lymphocytes.
AB  - Recent evidence has shown that translocation frequencies decline over time. This
      phenomenon might be explained by the co-occurrence of translocations in cells
      that also contain dicentrics, in which case translocations would be eliminated as
      a by-product of selection against dicentrics. Alternatively, a fraction of
      translocations may themselves be lethal. Here we describe our initial approaches
      to develop mathematical models to test whether the decline in translocation
      frequencies results from the first, the second, or a combination of these two
      possibilities. The models assumed that all chromosome exchanges were simple,
      i.e., were comprised of dicentrics as well as one-way and two-way translocations.
      Complex aberrations (three or more breaks in two or more chromosomes) were not
      modeled, nor were fragments or intrachromosomal exchanges (rings, inversions). We
      tested the models using Monte Carlo simulations, and then we fitted the models to
      data describing chromosome aberration frequencies induced by a single acute in
      vitro exposure to (137)Cs gamma rays in human peripheral blood lymphocytes from
      two donors. Chromosome painting was used to enumerate translocations and
      dicentrics from 2 to 7 days after exposure. Our results indicate that in donor
      no. 2, the decline in translocation frequencies occurs as a by-product of
      selection against dicentrics. However, in donor no. 1, whose cells appeared more
      radiosensitive than cells from donor no. 2, up to 40% of the one-way
      translocations may themselves be lethal at high doses, although calculations
      indicate that two-way translocations do not cause lymphocyte mortality.
      Individual variation in the probability that translocations are lethal to cells
      appears to be important, and one-way translocations appear to be lethal more
      often than two-way translocations. Within the limits of these models, these
      findings indicate that both postulated mechanisms, i.e. inherent lethality and
      selection against dicentrics in the same cells, contribute to the loss of both
      one-way and two-way translocations.

PMID- 11966321
TI  - Deficiency in nuclear accumulation of G22p1 and Xrcc5 proteins in hyper
      radiosensitive Long-Evans Cinnamon (LEC) rat cells after X irradiation.
AB  - The DNA-dependent protein kinase (DNA-PK) complex has been implicated in the
      repair of DNA double-strand breaks (DSBs). DNA-PK is a heterotrimeric protein
      complex comprised of two components: a large catalytic subunit, Prkdc, with
      serine/threonine kinase activity and a DNA-targeting component, G22p1 and Xrcc5.
      In previous report, we showed that approximately 80% of the G22p1 and Xrcc5
      proteins were observed in the cytoplasm of rat fibroblasts, and that nuclear
      translocation of the proteins from the cytoplasm is important for the repair of
      DNA DSBs. In the present study, we showed that nuclear accumulation of the G22p1
      and Xrcc5 proteins was not observed in fibroblasts from a mutant strain of Long
      Evans Cinnamon (LEC) rat that has an enhanced radiosensitivity and a reduced
      level of repair of DSBs after X irradiation. Nuclear translocation of the
      proteins was observed in both LEC rat cells and control rat cells with normal
      radiosensitivity at 5 min after X irradiation. Although high levels of G22p1 and
      Xrcc5 proteins were observed in the nuclei of control rat cells until 60 min
      postirradiation, the amounts of the proteins decreased rapidly in the nuclei of
      LEC rat cells in the first 10 min after X irradiation. These findings suggest
      that there are some defects in maintaining the levels of G22p1 and Xrcc5 proteins
      in the nuclei of LEC rat cells. An analysis of fibroblasts from backcross rats
      showed that the deficiency in nuclear accumulation of G22p1 and Xrcc5 proteins is
      genetically linked to enhanced radiosensitivity. Since the nucleotide sequences
      of the G22p1 and Xrcc5 genes of the LEC rats coincided with those of the control
      rats, the deficiency in nuclear accumulation may not be caused by mutations of
      the G22p1 and Xrcc5 proteins.

PMID- 11966322
TI  - DNA-PK and ATM are required for radiation-enhanced integration.
AB  - Ionizing radiation is known to improve transfection of exogenous DNA, a process
      we have termed radiation-enhanced integration. Previous observations have
      demonstrated that Ku proteins are critical for radiation-enhanced integration.
      Since Ku proteins form the DNA-binding domain of DNA-PK and since DNA-PK is
      important in nonhomologous DNA end joining, it was hypothesized that DNA-PK
      function might be important for radiation-enhanced integration. The ATM protein
      has been shown to be important in the recognition of a variety of types of DNA
      damage and to associate with DNA-PK under certain conditions. It was thus
      hypothesized that ATM might also play a role in radiation-enhanced integration.
      To test these hypotheses, radiation-enhanced integration was measured in hamster
      cells that are defective in the catalytic subunit of DNA-PK and in human cells
      containing mutant ATM. Radiation-enhanced integration was not detected in any of
      the cell lines with mutant PRKDC (also known as DNA-PKcs), but it was present in
      cells of the same lineage with wild-type PRKDC. Radiation-enhanced integration
      was defective in cells lacking kinase activation. ATM-deficient cell lines also
      showed defective radiation-enhanced integration. These data demonstrate that DNA
      PK and ATM must both be active for radiation-enhanced integration to be observed.

PMID- 11966323
TI  - Manganese superoxide dismutase (SOD2) inhibits radiation-induced apoptosis by
      stabilization of the mitochondrial membrane.
AB  - To define the molecular pathways involved in radiation-induced apoptosis and the
      role of the mitochondria, 32D cl 3 hematopoietic cells and subclones
      overexpressing either the human manganese superoxide dismutase (SOD2) transgene
      (1F2 and 2C6) or BCL2L1 (also known as Bcl-xl) transgene (32D-Bcl-xl) were
      compared for their response to radiation at the subcellular level, comparing
      nuclear to mitochondrial localized pathways. All cell lines showed complete
      detectable DNA repair by 30 min after irradiation, and clearly delayed migration
      of BAX and active stress-activated protein (SAP) kinases MAPK1 (also known as
      p38) and MAPK8 (also known as JNK1) to the mitochondria at 3 h. Radioresistant
      clonal lines 1F2, 2C6 and 32D-Bcl-xl showed significant decreases in
      mitochondrial membrane permeability, cytochrome C release, caspase 3 and
      poly(adenosine diphosphate-ribose) polymerase (PARP) activation at 6-12 h, and in
      apoptosis at 24 h. Since the nuclear-to-cytoplasm events preceding the release of
      cytochrome C were similar in all cell lines, and increased expression of either
      the SOD2 or the BCL2L1 transgene provided radiation protection, we conclude that
      events at the level of the mitochondria are critically involved in radiation
      induced apoptosis.

PMID- 11966324
TI  - Properties of selected S-nitrosothiols compared to nitrosylated WR-1065.
AB  - WR-1065 ([N-mercaptoethyl]-1-3-diaminopropane), the active form of the aminothiol
      drug Ethyol/Amifostine, protects against toxicity caused by radiation,
      chemotherapy and endotoxin. Because WR-1065 and other thiols readily bind nitric
      oxide (NO), injurious conditions or therapies that induce the production or
      mobilization of NO could alter the effects of WR-1065. S-Nitrosothiols were
      prepared from various thiols by a standard method to compare properties and
      stability. Heteromolecular quantum correlation 2D nuclear magnetic resonance was
      used to characterize nitrosylated glutathione (GSH) and WR-1065; both S- and N
      nitrosothiols were observed, depending on the experimental conditions. Three
      categories of S-nitrosothiol stability were observed: (1) highly stable, with
      t(1/2) > 8 h, N-acetyl-L-cysteine nitrosothiol (t(1/2) 15 h) > GSH nitrosothiol
      (t(1/2) 8 h); (2) intermediate stability, t(1/2) approximately 2 h, cysteamine
      nitrosothiol and WR-1065 nitrosothiol; and (3) low stability, t(1/2) < 1 h,
      cysteine nitrosothiol and Captopril nitrosothiol. Similar relative rates were
      observed for Hg(+2)-induced denitrosylation: WR-1065 reacted faster than GSH
      nitrosothiol, while GSH nitrosothiol reacted faster than N-acetyl-L-cysteine
      nitrosothiol. Mostly mediated by mixed-NPSH disulfide formation, the activity of
      the redox-sensitive cysteine protease, cathepsin H, was inhibited by the S
      nitrosothiols, with WR-1065 nitrosothiol > cysteine nitrosothiol > N-acetyl-L
      cysteine nitrosothiol and GSH nitrosothiol. These observations indicate that,
      relative to other nitrosylated non-protein thiols, the S-nitrosothiol of WR-1065
      is an unstable non-protein S-nitrosothiols with a high reactive potential in the
      modification of protein thiols.

PMID- 11966325
TI  - Formation of modified DNA bases in cells exposed either to gamma radiation or to
      high-LET particles.
AB  - The aim of the present study was to measure the formation of eight base
      modifications in the DNA of cells exposed to either low-LET ((60)Co gamma rays)
      or high-LET ((12)C(6+) particles) radiation. For this purpose, a recently
      optimized HPLC-MS/MS method was used subsequent to DNA extraction and hydrolysis.
      The background level of the measured modified bases and nucleosides was shown to
      vary between 0.2 and 2 lesions/10(6) bases. Interestingly, thymidine glycols
      constitute the main radiation-induced base modifications, with an overall yield
      of 0.097 and 0.062 lesion/10(6) bases per gray for gamma rays and carbon heavy
      ions, respectively. Both types of radiations generate four other major
      degradation products, in the following order of decreasing importance: FapyGua >
      5-HmdUrd > 5-FordUrd > 8-oxodGuo. The yields of formation of FapyAde and 8-oxoAde
      are one order of magnitude lower than those of the related guanine modifications,
      whereas the radiation-induced generation of 5-OHdUrd was below the limit of
      detection of the assay. The efficiency for both types of radiation to generate
      base damage in cellular DNA is low because the highest yield per gray was 0.097
      thymine glycols per 10(6) DNA bases. As a striking observation, the yield of
      formation of the measured DNA lesions was found to be, on average, twofold lower
      after exposure to high-LET radiation ((12)C(6+)) than after exposure to low-LET
      gamma radiation. These studies show that the HPLC-MS/MS assay provides an
      accurate, reliable and sensitive method for measuring cellular DNA base damage.

PMID- 11966326
TI  - Salivary gland-sparing prophylactic pilocarpine treatment has no effect on tumor
      regrowth after irradiation.
AB  - Radiotherapy of head and neck cancer frequently damages the salivary glands.
      Prophylactic administration of the muscarinic receptor agonist pilocarpine
      reduces subsequent radiation damage to the salivary glands in rats, but its
      effects on tumor cell radiosensitivity and tumor regrowth after irradiation had
      not been assessed. In the current study, we first tested the effect of
      pilocarpine on clonogenic cell survival in vitro. No effect of pilocarpine on
      radiosensitivity was observed in a panel of cell lines either with or without
      expression of muscarinic receptors. Second, a single dose of pilocarpine known to
      protect salivary gland tissue from radiation damage was given to rats
      transplanted with subcutaneously growing rhabdomyosarcomas 1 h prior to
      irradiation with a single dose of 35 Gy. No alterations in growth delay were
      detected (26 +/- 2 days for controls compared to 26 +/- 2 days for pilocarpine
      treatment). Our data indicate that pilocarpine pretreatment, which has been shown
      previously to protect salivary glands from radiation, does not protect tumor
      cells or tumors. Use of this drug therefore may lead to therapeutic gain in the
      treatment of head and neck cancer.

PMID- 11966327
TI  - Toward a consensus on radiobiology teaching to radiation oncology residents.
AB  - There are approximately 82 radiation oncology residency programs in the United
      States, which provide training opportunities for about 400 residents. All
      accredited radiation oncology residency programs must have at least one basic
      scientist on the faculty, and it is these individuals who often assume, wholly or
      in part, the responsibility of teaching radiation and cancer biology to radiation
      oncology residents in preparation for the American College of Radiology (ACR) In
      Training Examination in Radiation Oncology and the American Board of Radiology
      (ABR) written examinations. In response to a perceived lack of uniformity in
      radiation and cancer biology curricula currently being taught to residents and a
      perceived lack of guidance for instructors in formulating course content for this
      population, a special session was presented at the Forty-eighth Annual Radiation
      Research Society meeting on April 23, 2001. The session, entitled "Toward a
      Consensus on Radiobiology Teaching to Radiation Oncology Residents", was focused
      on issues related to teaching radiobiology to radiation oncology residents and
      targeted for individuals who actively teach radiation and cancer biology as well
      as coordinators of residency training programs. The speakers addressed current
      challenges and future problems facing instructors and programs. Among these were
      lack of feedback on resident performance on ABR and ACR written examinations and
      on course content, uncertainty about what topics residents must know to pass the
      ABR examination, and, in the near future, a reduction (due to retirement) of
      instructors qualified to teach radiobiology. This article provides a synopsis of
      the information that was presented during that session, offers a glimpse into how
      the ABR and ACR examinations are prepared and details of the content of past and
      future examinations, and summarizes the activities of the Joint Working Group on
      Radiobiology Teaching which was formed to educate instructors, to establish a
      consensus for course curricula, and to improve the overall quality of resident
      teaching.

PMID- 11966328
TI  - Radiation scientists and homeland security.
AB  - Radiation scientists represent an important resource in homeland defense.
      Security analysts worry that a crude but deadly radiological bomb might be
      fashioned from stolen nuclear material and a few sticks of dynamite. Such a
      device could kill dozens, hundreds, and possibly thousands and could contaminate
      a square mile or more. Emergency workers may call upon radiation scientists to
      aid the injured. Educational materials are available on the ACR, ASTRO, and RRS
      websites, linked to the Armed Forces Radiobiology Research Institute and the Oak
      Ridge National Laboratory, to provide radiation workers material that they can
      use to help emergency room and civil defense personnel after a terrorist attack.
      Radiation scientists are urged to obtain these materials and contact their local
      hospital and public health authorities to volunteer their services and expertise.

PMID- 11966329
TI  - Incidence and temporal patterns of adaptive behavior change in adults with mental
      retardation.
AB  - The age-associated incidence of significant decline in adaptive behavior and the
      temporal pattern of decline in specific functional skill domains were examined in
      646 adults with mental retardation through 88 years of age. Cumulative incidence
      of significant decline for adults with Down syndrome increased from less than.04
      at age 50 to.67 by age 72, whereas cumulative incidence of significant decline
      for adults with mental retardation without Down syndrome increased from less
      than.02 at age 50 to.52 at age 88. Among adults experiencing overall decline,
      four clusters of behaviors were identified based upon the sequence and magnitude
      of changes, suggesting a pattern of loss not unlike that noted in the population
      without mental retardation with dementia.

PMID- 11966330
TI  - Pneumonia frequencies with different enteral tube feeding access sites.
AB  - In a retrospective review at a long-term care facility serving persons with
      mental retardation, I discovered a noteworthy difference in the frequency of
      pneumonia experienced by persons receiving nutrition via a surgically created
      jejunostomy as compared to a gastrostomy. Over a 24-month period, 25 people being
      fed via a gastrostomy tube experienced 40 cases of pneumonia during 508 person
      months of observation, whereas 5 individuals being fed via a jejunostomy tube did
      not experience any cases of pneumonia during 96 person-months of observation. The
      enteral feeding access sites for these individuals were established at various
      times as long ago as 12 years prior to this review period. Selection of the
      specific access site for each individual was not randomized.

PMID- 11966331
TI  - Assessing personality traits of individuals with mental retardation.
AB  - Psychometric properties for a new instrument, the EZ-Personality Questionnaire
      designed to assess the functioning of students with cultural-familial mental
      retardation, are presented. The analysis of data from 661 participants yielded a
      37-item, seven-scale instrument that confirmed the five hypothesized factors of
      Positive Reaction Tendency, Negative Reaction Tendency, Effectance Motivation,
      Expectancy of Success, and Outerdirectedness and identified two additional
      factors of Curiosity/Creativity and Obedience. Separate studies were conducted to
      establish the concurrent and construct validity of the instrument. Reliability
      was examined through split-half and test-retest analyses. All psychometric
      indices were within acceptable levels, resulting in an instrument with potential
      applications in research, education, and clinical settings.

PMID- 11966332
TI  - Effects of environmental events on smiling and laughing behavior in Angelman
      syndrome.
AB  - Angelman syndrome is a neurogenetic disorder associated with unique behaviors and
      characteristics, including an unusually happy expression, inability to speak,
      ataxia, mental retardation, and abnormal EEG. Previous research has suggested
      that smiling and laughing behaviors in Angelman syndrome are inappropriate,
      excessive, and dissociated from contextual events. In the present study, the
      variability of smiling and laughing behaviors of 3 individuals with Angelman
      syndrome was examined across typical social contexts. Results indicate that
      laughing and smiling increased during social situations and occurred at low
      levels during non-social situations. The behaviors, therefore, did not occur
      totally inappropriately, as has been suggested. The findings illustrate the need
      to divert attention to the examination of environmental influences on purported
      phenotypic behavior in genetic syndromes.

PMID- 11966333
TI  - Differences in cardiovascular disease risk between nondiabetic adults with mental
      retardation with and without Down syndrome.
AB  - A reduced expression of the insulin resistance syndrome, a common neuroendocrine
      disorder underlying atherosclerosis, may play a role in reduced atherosclerosis
      in adults with Down syndrome. We compared selected components of the insulin
      resistance syndrome between 75 adults with Down syndrome and 70 with mental
      retardation due to other causes. After adjusting for age differences, residence,
      cigarette smoking, and medication use, women with Down syndrome had lower fasting
      plasma glucose and lower systolic blood pressure than comparison women. Men with
      Down syndrome had lower systolic and diastolic blood pressure than comparison
      men. Results suggest that women with Down syndrome may be less likely to express
      the insulin resistance syndrome, and men and women with Down syndrome may possess
      fewer atherosclerotic risk factors than the comparison groups.

PMID- 11966334
TI  - Behavioral treatment of self-injury, 1964 to 2000.
AB  - A quantitative analysis of behavioral research on the treatment of self-injurious
      behavior (SIB) over the past 35 years is provided. A literature search covering
      the period from 1964 to 2000 yielded 396 articles (706 participants) on the
      treatment of SIB. Most research participants have been male and diagnosed with
      severe/profound mental retardation. The use of reinforcement-based interventions
      has increased during the past decade, whereas the use of punishment-based
      interventions has decreased slightly; both of these trends coincide with the
      increase in the use of functional assessments. Most treatments have been highly
      effective in reducing SIB; nevertheless, the disorder persists in spite of an
      abundance of research, suggesting that a greater emphasis should be placed on
      prevention.

PMID- 11966335
TI  - Behavior problems of children with autism, parental self-efficacy, and mental
      health.
AB  - Self-efficacy has been identified in the general parenting literature as an
      important variable affecting parent outcomes. In the present study, 26 mothers
      and 20 fathers of children with autism reported on their self-efficacy, anxiety,
      and depression. Teachers rated the behavior problems of the children. Regression
      analyses showed that self-efficacy mediated the effect of child behavior problems
      on mothers' anxiety and depression, but there was no evidence that it functioned
      as a mediator for fathers. However, there was evidence that self-efficacy
      moderated the effect of child behavior problems on fathers' anxiety. No evidence
      for the moderating effect of self-efficacy was apparent for mothers.
      Methodological issues and the theoretical and practical implications of these
      results are discussed.

PMID- 11966336
TI  - Is high-sensitivity C-reactive protein an effective screening test for
      cardiovascular risk?
AB  - We evaluate the suggestion that high-sensitivity C-reactive protein testing be
      used for risk assessment in the primary prevention of cardiovascular disease,
      using the criteria proposed by the Guide to Clinical Preventive Services
      developed by the US Preventive Services Task Force. We conclude that at present,
      none of the 3 major criteria--accuracy, reliability, and likelihood of beneficial
      intervention--are satisfied.

PMID- 11966337
TI  - Intravascular catheter-related infections: new horizons and recent advances.
AB  - BACKGROUND: Central venous catheters have become essential devices for the
      management of critically and chronically ill patients; however, their use is
      often complicated by catheter-related bloodstream infections (CRBSIs), many of
      which could be prevented. METHODS: This report is based on a literature review of
      more than 100 published articles in intravascular catheter-related infections.
      This review focuses on the most recent advances in the methods of diagnosis of
      CRBSI as they relate to its pathogenesis and on novel preventive techniques and
      approaches to management. RESULTS: Catheter-related bloodstream infections may be
      diagnosed by different methods, including simultaneous quantitative blood
      cultures, with the central blood culture yielding at least 5-fold colony-forming
      units greater than the peripheral blood culture, and simultaneous blood cultures,
      whereby the catheter-drawn blood culture becomes positive at least 2 hours before
      the peripheral blood culture. Novel preventive techniques include the use of
      ionic silver, an anticoagulant/antimicrobial flush solution, a new aseptic hub,
      and antimicrobial impregnation of catheters and dressings. Management of CRBSIs
      should be based on whether the infection is complicated or uncomplicated.
      CONCLUSIONS: Novel technologies that have been proved to aid in the diagnosis and
      prevention of CRBSIs should be considered in clinical practice. The management
      approach should be based on the type of microorganism causing the infection and
      on whether the infection is complicated or uncomplicated.

PMID- 11966338
TI  - Antithrombotic treatment and the incidence of angina pectoris.
AB  - BACKGROUND: In primary prevention, anticoagulation with warfarin sodium to an
      international normalized ratio of 1.5 and 75 mg of aspirin per day each reduced
      the incidence of coronary heart disease (CHD). Effects on the development of
      angina pectoris and total CHD (resulting from angina, myocardial infarction, and
      coronary death) have been assessed, particularly in light of recent evidence that
      warfarin may have a "durable effect" on CHD through effects on the pathologic
      condition of the vessel walls involved. METHODS: The Thrombosis Prevention Trial
      was carried out in 5499 men aged 45 through 69 years who were at increased risk
      of CHD. The trial was factorial, with 1 group taking active warfarin and active
      aspirin, 1 taking active warfarin and placebo aspirin, 1 taking placebo warfarin
      and active aspirin, and 1 taking double placebo treatment. In addition to those
      with myocardial infarction and coronary death, men developing angina pectoris
      after entry to the trial were identified. RESULTS: Warfarin appeared to reduce
      the incidence of stable angina by 16% (95% confidence interval [CI], -14 to 38),
      although not significantly (P =.26), while aspirin increased the incidence by 39%
      (95% CI, 0 to 91) (P =.05). The incidence of stable angina was 37% (95% CI, -1 to
      60) less in those taking warfarin than in those taking aspirin (P =.05). Warfarin
      reduced total CHD by 18% (95% CI, 4 to 30) (P =.01), while the reduction due to
      aspirin was 8% (95% CI, -10 to 22) (P =.36). CONCLUSIONS: The results are
      compatible with the concept of a durable effect of warfarin on the chronic
      pathologic conditions underlying angina, although this has not been established
      with certainty. Further research is needed to confirm or refute our findings,
      because they carry potentially important implications for the primary prevention
      of CHD with the use of antithrombotic agents.

PMID- 11966339
TI  - Identifying undiagnosed human immunodeficiency virus: the yield of routine,
      voluntary inpatient testing.
AB  - BACKGROUND: Despite current recommendations for human immunodeficiency virus
      (HIV) counseling and testing among patients admitted to hospitals with at least a
      1% prevalence of HIV infection, an estimated 300 000 people in the United States
      remain unaware of their HIV infection. METHODS: We implemented the Think HIV
      program, which offered voluntary HIV counseling and testing to patients admitted
      to the medical service of a Boston, Mass, teaching hospital. We compared the
      results of this effort with testing results from a 15-month historical control
      period. RESULTS: Patients admitted during the program period were 3.4 times more
      likely to undergo testing for HIV than those admitted during the control period
      (95% confidence interval [CI], 2.8-4.1). The testing program detected
      approximately 2 new diagnoses of HIV infection per month, compared with 1 per
      month during the control period. Patients who underwent testing during the
      program, and who likely would not have done so without this initiative, had an
      estimated prevalence of HIV infection of 3.8% (95% CI, 1.8%-5.8%). CONCLUSIONS:
      Testing efforts for HIV targeted to only symptomatic patients are inadequate to
      identify the one third of HIV-seropositive people in the United States who are
      unaware of their infection. We have shown that in a single urban hospital,
      offering voluntary, routine inpatient HIV counseling and testing can be
      successful as a screening program by identifying a substantial number of patients
      with undiagnosed HIV. These patients then can be informed, counseled, and linked
      to care and treatment. Seventy-two hospitals nationwide have demographics similar
      to those of the study hospital, suggesting that these results are generalizable
      to many urban hospitals.

PMID- 11966340
TI  - Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep
      Heart Health Study.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is common, but largely undiagnosed
      in the general population. Information on demographic patterns of SDB occurrence
      and its predictive factors in the general population is needed to target high
      risk groups that may benefit from diagnosis. METHODS: The sample comprised 5615
      community-dwelling men and women aged between 40 and 98 years who were enrolled
      in the Sleep Heart Health Study. Data were collected by questionnaire, clinical
      examinations, and in-home polysomnography. Sleep-disordered breathing status was
      based on the average number of apnea and hypopnea episodes per hour of sleep
      (apnea-hypopnea index [AHI]). We used multiple logistic regression modeling to
      estimate cross-sectional associations of selected participant characteristics
      with SDB defined by an AHI of 15 or greater. RESULTS: Male sex, age, body mass
      index, neck girth, snoring, and repeated breathing pause frequency were
      independent, significant correlates of an AHI of 15 or greater. People reporting
      habitual snoring, loud snoring, and frequent breathing pauses were 3 to 4 times
      more likely to have an AHI of 15 or greater vs an AHI less than 15, but there
      were weaker associations for other factors with an AHI of 15 or greater. The odds
      ratios (95% confidence interval) for an AHI of 15 or greater vs an AHI less than
      15 were 1.6 and 1.5, respectively, for 1-SD increments in body mass index and
      neck girth. As age increased, the magnitude of associations for SDB and body
      habitus, snoring, and breathing pauses decreased. CONCLUSIONS: A significant
      proportion of occult SDB in the general population would be missed if screening
      or case finding were based solely on increased body habitus or male sex.
      Breathing pauses and obesity may be particularly insensitive for identifying SDB
      in older people. A better understanding of predictive factors for SDB,
      particularly in older adults, is needed.

PMID- 11966341
TI  - Anger in young men and subsequent premature cardiovascular disease: the
      precursors study.
AB  - BACKGROUND: Anger can trigger myocardial ischemia and may be an independent risk
      factor for coronary heart disease, but its effect on early compared with late
      onset of disease is unclear. METHODS: We performed a prospective study of 1055
      men followed up for 32 to 48 years to examine the risk of premature and total
      cardiovascular disease (CVD) associated with anger responses to stress during
      early adult life. Highest level of anger was defined as a self-report of all 3
      possible anger reactions to stress (expressed or concealed anger, gripe sessions,
      and irritability) on a checklist questionnaire administered in medical school.
      Premature disease was defined as events before age 55 years. RESULTS: During a
      median follow-up period of 36 years, 205 men developed CVD (cumulative incidence
      at 76 years, 34.5%), of whom 77 men developed premature disease (cumulative
      incidence before 55 years, 7.9%). The highest level of anger was associated with
      an increased risk of premature CVD (adjusted relative risk, 3.1; 95% confidence
      interval, 1.1-8.6), including premature coronary heart disease (relative risk,
      3.5; 95% confidence interval, 1.1-11.8) and premature myocardial infarction
      (relative risk, 6.4; 95% confidence interval, 1.8-22.3), compared with lower
      levels of anger. When CVD events after age 55 years were included, there was no
      longer a statistically significant association between anger and CVD. CONCLUSION:
      High level of anger in response to stress in young men is associated with an
      increased risk of subsequent premature CVD, particularly myocardial infarction.

PMID- 11966342
TI  - Simplification of the diagnostic management of suspected deep vein thrombosis.
AB  - BACKGROUND: The standard diagnostic approach in patients with suspected deep vein
      thrombosis is to repeat the compression ultrasonography after 1 week in all
      patients with an initial normal result. We hypothesized that a normal finding of
      a D-dimer assay safely obviates the need for repeated ultrasonography. In
      addition, we evaluated the potential value of a pretest probability assessment
      for this purpose. METHODS: At presentation, consecutive outpatients with
      suspected thrombosis underwent independent assessment by means of ultrasonography
      of the proximal veins, a whole-blood D-dimer assay, and a pretest clinical model.
      Patients with normal ultrasonographic findings and an abnormal D-dimer assay
      result were scheduled for repeated ultrasonography. We evaluated the incidence of
      symptomatic venous thromboembolic complications during a 3-month follow-up, and
      the value of clinical pretest probability with ultrasonography or D-dimer assay
      in scenario analyses. RESULTS: We studied 1756 patients with prevalence of
      thrombosis of 22%. At entry, results of the D-dimer assay and ultrasonography
      were normal in 828 patients (47%). Of these, 6 returned with confirmed
      symptomatic venous thromboembolism (complication rate, 0.7%; 95% confidence
      interval [CI], 0.3%-1.6%). Repeated ultrasonography was avoided in 61% of the
      patients with an initial normal test result. Scenario analyses disclosed that the
      complication rate was 1.6% (95% CI, 0.8%-2.6%) in those with a low clinical
      pretest probability and a normal result of ultrasonography at referral, whereas
      this figure was 1.8% (95% CI, 0.9%-3.3%) in patients with a low clinical
      probability result and a normal result of the D-dimer assay at referral.
      CONCLUSIONS: It is safe to withhold repeated ultrasonography in patients with
      suspected deep vein thrombosis who have normal results of ultrasonograpy and the
      SimpliRED D-dimer assay at presentation. The combination of a low clinical
      pretest probability with a normal result of compression ultrasonography or the D
      dimer assay appears to be equally safe in refuting the diagnosis of deep vein
      thrombosis.

PMID- 11966343
TI  - Primary prevention of high blood cholesterol concentrations in the United States.
AB  - BACKGROUND: Mean concentrations of total cholesterol (TC) among adults have
      declined in the United States for decades. Whether the decline has been owing to
      prevention of high TC levels or treatment of high TC levels once present is not
      known. OBJECTIVE: To determine whether population-wide influences and/or the high
      risk approach have been operating to produce the well-known decline in mean TC
      concentration in the US population. METHODS: We examined changes in the
      distribution of TC levels across US birth cohorts as sampled in the National
      Health Examination Survey and the National Health and Nutrition Examination
      Surveys I, II, and III. We tested the hypotheses that the age-adjusted 10th,
      25th, 50th, 75th, and 90th percentiles of TC levels were lower in more recent US
      birth cohorts than in earlier cohorts. RESULTS: Data were analyzed for 49 536
      participants born between 1887 and 1975 and examined at ages 18 through 74 years
      between 1959 and 1994. The 10th, 25th, 50th, 75th, and 90th percentiles of TC
      levels (adjusted for age, race, and sex) were estimated to be lower by 3.4, 3.9,
      4.7, 5.7, and 7.1 mg/dL (0.09, 0.10, 0.12, 0.15, and 0.18 mmol/L), respectively,
      for every successive 10 years in date of birth (P<.001 for each estimate).
      CONCLUSIONS: The declines in TC levels associated with successive birth cohorts
      were greater at the upper aspect of the distribution, probably because of the
      combination of population influences and treatment effects. The differences seen
      at the lower percentiles support the contention that a strong prevention effect
      occurred in the US population from 1959 through 1994. Greater understanding of
      this dramatic shift in the distribution of TC levels could support future
      prevention efforts.

PMID- 11966344
TI  - Prophylaxis for human immunodeficiency virus-related Pneumocystis carinii
      pneumonia: using simulation modeling to inform clinical guidelines.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected patients receiving highly
      active antiretroviral therapy (HAART) have experienced a dramatic decrease in
      Pneumocystis carinii pneumonia (PCP), necessitating reassessment of clinical
      guidelines for prophylaxis. METHODS: A simulation model of HIV infection was used
      to estimate the lifetime costs and quality-adjusted life expectancy (QALE) for
      alternative CD4 cell count criteria for stopping primary PCP prophylaxis in
      patients with CD4 cell count increases receiving HAART and alternative agents for
      second-line PCP prophylaxis in those intolerant of trimethoprim-sulfamethoxazole
      (TMP/SMX). The target population was a cohort of HIV-infected patients in the
      United States with initial CD4 cell counts of 350/microL who began PCP
      prophylaxis after their first measured CD4 lymphocyte count less than 200/microL.
      Data were from randomized controlled trials and other published literature.
      RESULTS: For patients with CD4 cell count increases during HAART, waiting to stop
      prophylaxis until the first observed CD4 cell count was greater than 300/microL
      prevented 9 additional cases per 1000 patients and cost $9400 per quality
      adjusted life year (QALY) gained compared with stopping prophylaxis at
      200/microL. For patients intolerant of TMP/SMX, using dapsone increased QALE by
      2.7 months and cost $4500 per QALY compared with no prophylaxis. Using atovaquone
      rather than dapsone provided only 3 days of additional QALE and cost more than
      $1.5 million per QALY. CONCLUSIONS: Delaying discontinuation of PCP prophylaxis
      until the first observed CD4 cell count greater than 300/microL is cost-effective
      and provides an explicit "PCP prophylaxis stopping criterion." In TMP/SMX
      intolerant patients, dapsone is more cost-effective than atovaquone.

PMID- 11966345
TI  - Disparities in the diagnosis and pharmacologic treatment of high serum
      cholesterol by race and ethnicity: data from the Third National Health and
      Nutrition Examination Survey.
AB  - BACKGROUND: Serum cholesterol is one of the most important modifiable risk
      factors for coronary artery disease. There are conflicting data on racial and
      ethnic variation in the treatment of high cholesterol. METHODS: We analyzed data
      from the Third National Health and Nutrition Examination Survey, a nationally
      representative cross-sectional survey conducted between 1988 and 1994.
      Participants included 7679 white, 4467 African American, and 4113 Mexican
      American adults older than 25 years who completed the household adult
      questionnaire. The adjusted odds of serum cholesterol screening and of taking a
      prescription medication to lower serum cholesterol among African Americans and
      Mexican Americans were compared with those of whites, controlling for differences
      in age, sex, income, educational level, insurance status, comorbid illness, and
      having a regular source of health care. RESULTS: African Americans and Mexican
      Americans were significantly less likely than whites to report ever having had
      their blood cholesterol checked (odds ratio, 0.7 for both; P<.001). Among
      individuals with high cholesterol who were told to take a medication, African
      Americans (P<.001) and Mexican Americans (P =.05) were less likely than whites to
      be taking a cholesterol-lowering agent (odds ratios, 0.3 and 0.5, respectively).
      Individuals who reported being told they had high cholesterol had significantly
      higher serum cholesterol measurements (from the laboratory examination) than
      those who reported being told their cholesterol was not high (234 vs 198 mg/dL
      [6.05 vs 5.12 mmol/L]; P<.001). CONCLUSIONS: African Americans and Mexican
      Americans were less likely to report serum cholesterol screening than whites.
      Even when identified as having high cholesterol that required medication, African
      Americans and Mexican Americans were less likely than whites to be taking
      cholesterol-lowering agents.

PMID- 11966346
TI  - Gastric and duodenal safety of daily alendronate.
AB  - BACKGROUND: Isolated case reports of gastric ulcers after alendronate sodium use
      raised concern about the gastroduodenal safety of daily alendronate. This study
      was conducted to estimate the excess risk of hospitalizations for gastric or
      duodenal perforations, ulcers, and bleeding associated with alendronate use.
      PARTICIPANTS AND METHODS: Study subjects were 6432 men and women, 35 years or
      older. The subjects were members of 8 health maintenance organizations who were
      dispensed alendronate from October 1995 through September 1997. There was also a
      group of 33 176 age-, sex-, and health maintenance organization-matched unexposed
      persons. Because of concerns that osteoporosis might confound the association
      between alendronate use and perforation, ulcer, or bleeding, a second comparison
      group of 9776 women, 60 years or older, who had osteoporotic fractures was
      assembled. Hospitalizations for gastroduodenal events were identified by
      discharge diagnosis codes in automated claims records, and confirmed by manual
      record review. RESULTS: Based on the 14 confirmed events in the alendronate group
      and 35 in the unexposed group, the crude incidence rate ratio of gastroduodenal
      perforation, ulcer, or bleeding for the alendronate cohort was 3.0. The incidence
      rate ratio was 1.8 (95% confidence interval, 0.8-3.9) after control for prior
      hospitalizations, comorbidity, and recent exposure to prescription nonsteroidal
      anti-inflammatory drugs and oral corticosteroids. The crude incidence ratio rate
      for the age, sex, and health maintenance organizations-restricted cohort of
      alendronate users relative to the fracture cohort was 1.1 and the adjusted
      incidence rate ratio was 1.1 (95% confidence interval, 0.6-2.2). CONCLUSIONS:
      Osteoporosis and related factors appear to play an important role in the
      relationship between alendronate use and confirmed gastroduodenal perforation,
      ulcer, or bleeding; a substantial fraction of the increased risk we observed for
      alendronate users in the unadjusted analysis was the result of confounding.

PMID- 11966347
TI  - Distinguishing complementary medicine from alternative medicine.

PMID- 11966348
TI  - Spiritual informed consent for CAM.

PMID- 11966350
TI  - Full adherence to HAART: is it really necessary?

PMID- 11966352
TI  - Trichinellosis is unlikely to be responsible for Mozart's death.

PMID- 11966354
TI  - Volunteerism in the care of the uninsured.

PMID- 11966355
TI  - Refusal of endoscopy in cirrhotic patients with Child-Pugh class a without prior
      variceal bleeding: an internist dilemma.

PMID- 11966356
TI  - Depressive symptoms and negative outcomes in older hospitalized patients.

PMID- 11966358
TI  - Tumor markers in malignant ascites.

PMID- 11966361
TI  - Preoperative evaluation of the patient with hypertension.

PMID- 11966362
TI  - Researchers wrestle with spread and control of emerging infections.

PMID- 11966363
TI  - World health focus of Fogarty International Center.

PMID- 11966368
TI  - Advantages and limitations of the hospitalist movement.

PMID- 11966369
TI  - Advantages and limitations of the hospitalist movement.

PMID- 11966370
TI  - Advantages and limitations of the hospitalist movement.

PMID- 11966371
TI  - Advantages and limitations of the hospitalist movement.

PMID- 11966372
TI  - Advantages and limitations of the hospitalist movement.

PMID- 11966373
TI  - Advantages and limitations of the hospitalist movement.

PMID- 11966374
TI  - Advantages and limitations of the hospitalist movement.

PMID- 11966376
TI  - Sudden-onset sleep in Parkinson disease.

PMID- 11966378
TI  - Chelation therapy for patients with ischemic heart disease.

PMID- 11966379
TI  - Chelation therapy for patients with ischemic heart disease.

PMID- 11966381
TI  - Effect of high-dose amoxicillin on the prevalence of penicillin-resistant
      Streptococcus pneumoniae in rural Alaska.

PMID- 11966382
TI  - Dairy consumption, obesity, and the insulin resistance syndrome in young adults:
      the CARDIA Study.
AB  - CONTEXT: Components of the insulin resistance syndrome (IRS), including obesity,
      glucose intolerance, hypertension, and dyslipidemia, are major risk factors for
      type 2 diabetes and heart disease. Although diet has been postulated to influence
      IRS, the independent effects of dairy consumption on development of this syndrome
      have not been investigated. OBJECTIVE: To examine associations between dairy
      intake and incidence of IRS, adjusting for confounding lifestyle and dietary
      factors. DESIGN: The Coronary Artery Risk Development in Young Adults (CARDIA)
      study, a population-based prospective study. SETTING AND PARTICIPANTS: General
      community sample from 4 US metropolitan areas of 3157 black and white adults aged
      18 to 30 years who were followed up from 1985-1986 to 1995-1996. MAIN OUTCOME
      MEASURE: Ten-year cumulative incidence of IRS and its association with dairy
      consumption, measured by diet history interview. RESULTS: Dairy consumption was
      inversely associated with the incidence of all IRS components among individuals
      who were overweight (body mass index > or =25 kg/m(2)) at baseline but not among
      leaner individuals (body mass index < 25 kg/m(2)). The adjusted odds of
      developing IRS (2 or more components) were 72% lower (odds ratio, 0.28; 95%
      confidence interval, 0.14-0.58) among overweight individuals in the highest (> or
      =35 times per week, 24/102 individuals) compared with the lowest (<10 times per
      week, 85/190 individuals) category of dairy consumption. Each daily occasion of
      dairy consumption was associated with a 21% lower odds of IRS (odds ratio, 0.79;
      95% confidence interval, 0.70-0.88). These associations were similar for blacks
      and whites and for men and women. Other dietary factors, including macronutrients
      and micronutrients, did not explain the association between dairy intake and IRS.
      CONCLUSIONS: Dietary patterns characterized by increased dairy consumption have a
      strong inverse association with IRS among overweight adults and may reduce risk
      of type 2 diabetes and cardiovascular disease.

PMID- 11966383
TI  - Patient and caregiver characteristics and nursing home placement in patients with
      dementia.
AB  - CONTEXT: The decision to institutionalize a patient with dementia is complex and
      is based on patient and caregiver characteristics and the sociocultural context
      of patients and caregivers. Most studies have determined predictors of nursing
      home placement primarily according to patient or caregiver characteristics alone.
      OBJECTIVE: To develop and validate a prognostic model to determine the
      comprehensive predictors of placement among an ethnically diverse population of
      patients with dementia. DESIGN, SETTING, AND PARTICIPANTS: The Medicare
      Alzheimer's Disease Demonstration and Evaluation study, a prospective study at 8
      sites in the United States, with enrollment between December 1989 and December
      1994 of 5788 community-living persons with advanced dementia. MAIN OUTCOME
      MEASURES: Time to nursing home placement throughout a 36-month follow-up period,
      assessed by interview and review of Medicare records, and its association with
      patient and caregiver characteristics, obtained by interview at enrollment.
      RESULTS: Patients were divided into a development (n = 3859) and validation (n =
      1929) cohort. In the development cohort, the Kaplan-Meier estimates of nursing
      home placement throughout 1, 2, and 3 years were 22%, 40%, and 52%, respectively.
      After multivariate adjustment, patient characteristics that were associated with
      nursing home placement were as follows: black ethnicity (hazard ratio, 0.60; 95%
      confidence interval [CI], 0.48-0.74), Hispanic ethnicity (HR, 0.40; 95% CI, 0.28
      0.56) (both ethnicities were inversely associated with placement), living alone
      (HR, 1.74; 95% CI, 1.49-2.02), 1 or more dependencies in activities of daily
      living (HR, 1.38; 95% CI, 1.20-1.60), high cognitive impairment (for Mini-Mental
      Status Examination score < or =20: HR, 1.52; 95% CI, 1.33-1.73), and 1 or more
      difficult behaviors (HR, 1.30; 95% CI, 1.11-1.52). Caregiver characteristics
      associated with patient placement were age 65 to 74 years (HR, 1.17; 95% CI, 1.01
      1.37), age 75 years or older (HR, 1.55; 95% CI, 1.31-1.84), and high Zarit Burden
      Scale score (for highest quartile: HR, 1.73; 95% CI, 1.49-2.00). Patients were
      assigned to quartiles of risk based on this model. In the development cohort,
      patients in the first, second, third, and fourth quartile had a 25%, 42%, 64%,
      and 91% rate of nursing home placement at 3 years, respectively. In the
      validation cohort, the respective rates were 21%, 50%, 64%, and 89%. The C
      statistic for 3-year nursing home placement was 0.66 in the development cohort
      and 0.63 in the validation cohort. CONCLUSIONS: Patient and caregiver
      characteristics are both important determinants of long-term care placement for
      patients with dementia. Interventions directed at delaying placement, such as
      reduction of caregiver burden or difficult patient behaviors, need to take into
      account the patient and caregiver as a unit.

PMID- 11966384
TI  - Evaluation of restorative care vs usual care for older adults receiving an acute
      episode of home care.
AB  - CONTEXT: Illness and hospitalization often trigger functional decline among older
      persons. Home care services implemented for functional decline provide an
      opportunity to intervene to improve outcomes. OBJECTIVE: To compare functional
      status and the likelihood of remaining at home for persons receiving restorative
      care vs usual home care. DESIGN AND SETTING: Intervention using prospective
      individual matching conducted between November 1, 1998, and April 30, 2000. Six
      offices of a home care agency in Connecticut were used. One branch office served
      as the restorative care unit and the other 5 served as usual care offices.
      PARTICIPANTS: Patients receiving home care through the restorative care office
      who were 65 years or older; in receipt of Medicare-covered home care lasting at
      least 7 days; with absence of severe cognitive impairment; and not terminal,
      bedridden, or requiring total care were matched with patients from 1 of the usual
      care offices. The matching factors included age, sex, race, baseline self-care
      function, cognitive status, whether hospitalization preceded the home care
      episode, and date of the home care episode. Of the 712 eligible restorative care
      patients, 691 (97%) were matched with a usual care patient. INTERVENTION:
      Restorative care, provided by the home care agency nursing, therapy, and home
      health aide staff, was based on principles from geriatric medicine, nursing,
      rehabilitation, and goal attainment. MAIN OUTCOME MEASURES: Remaining at home,
      functional status at completion of the home care episode, and duration and
      intensity of home care episode. RESULTS: Compared with usual care, and after
      adjusting for baseline characteristics and other factors, restorative care was
      associated with a greater likelihood of remaining at home (82% vs 71%; odds ratio
      [OR], 1.99; 95% confidence interval [CI], 1.47-2.69) and a reduced likelihood of
      visiting an emergency department (10% vs 20%; OR, 0.44; 95% CI, 0.32-0.61). Home
      care episodes were shorter (mean [SD], 24.8 [26.8] days vs 34.3 [44.2] days; S = 
      17 821; P<.001). Restorative care patients had better mean (SD) scores than usual
      care patients in self-care (11.0 [2.1] vs 10.7 [2.5]; P =.07 after adjustment),
      home management (9.5 [2.9] vs 9.2 [3.0]; P =.05 after adjustment), and mobility
      (3.3 [0.8] vs 3.2 [0.9]; P =.02 after adjustment). CONCLUSIONS: This trial
      suggests that reorganizing the structure and goals of home care can enhance
      health outcomes of older patients without increasing health care utilization.

PMID- 11966385
TI  - Survival of blacks and whites after a cancer diagnosis.
AB  - CONTEXT: In recent years a theory that cancer biology is different in blacks and
      whites has gained prominence in reaction to epidemiologic observations that
      blacks have poorer survival than whites, even when diagnosed with cancer of
      similar severity. Yet, few studies have evaluated whether lower-quality treatment
      and shorter overall life expectancy due to a greater burden of other illnesses
      may explain the survival discrepancy. OBJECTIVE: To estimate the magnitude of
      overall and cancer-specific survival differences between blacks and whites who
      receive comparable treatment for similar-stage cancer. DATA SOURCES: We searched
      MEDLINE for English-language articles published from 1966 to January 2002 that
      reported on overall survival for black and white patients treated similarly for
      cancer. STUDY SELECTION: The abstracts or titles for 891 citations were
      independently examined by 2 authors. The full text was retrieved if the abstract
      mentioned both black and white patients, made some comment regarding either
      similarity of treatment received or presented an analysis based on the treatment
      received, and commented on survival. Studies were included if they included data
      for at least 10 black and 10 white patients; specified the cohort ascertainment
      method and what measures were undertaken to minimize loss to follow-up;
      summarized survival of both blacks and whites using actuarial measures; presented
      outcomes within stage, adjusted for stage, or based on cohorts with balanced
      stage distributions; and specified that blacks and whites in the study received
      similar treatment. We identified 89 unique cohorts in 54 articles that met our
      inclusion criteria. DATA EXTRACTION: Overall survival rates and hazard ratios
      (HRs) for death for blacks relative to whites were calculated. These were
      subsequently adjusted for rates of death due to causes other than the cancer
      under study to determine cancer-specific survival and cancer-specific HRs. DATA
      SYNTHESIS: Results represent 189 877 white and 32 004 black patients with 14
      different cancers. Compared with whites, blacks had an overall excess risk of
      death (HR, 1.16; 95% confidence interval [CI], 1.12-1.20). After correction for
      deaths due to other causes, the cancer-specific HR was 1.07 (95% CI, 1.02-1.13).
      Of the 14 cancers, blacks were at a significantly higher risk of cancer-specific
      death only for cancer of the breast, uterus, or bladder. CONCLUSIONS: Only modest
      cancer-specific survival differences are evident for blacks and whites treated
      comparably for similar-stage cancer. Therefore, differences in cancer biology
      between racial groups are unlikely to be responsible for a substantial portion of
      the survival discrepancy. Differences in treatment, stage at presentation, and
      mortality from other diseases should represent the primary targets of research
      and interventions designed to reduce disparities in cancer outcomes.

PMID- 11966386
TI  - The 2001 Bethesda System: terminology for reporting results of cervical cytology.
AB  - OBJECTIVES: The Bethesda 2001 Workshop was convened to evaluate and update the
      1991 Bethesda System terminology for reporting the results of cervical cytology.
      A primary objective was to develop a new approach to broaden participation in the
      consensus process. PARTICIPANTS: Forum groups composed of 6 to 10 individuals
      were responsible for developing recommendations for discussion at the workshop.
      Each forum group included at least 1 cytopathologist, cytotechnologist,
      clinician, and international representative to ensure a broad range of views and
      interests. More than 400 cytopathologists, cytotechnologists, histopathologists,
      family practitioners, gynecologists, public health physicians, epidemiologists,
      patient advocates, and attorneys participated in the workshop, which was convened
      by the National Cancer Institute and cosponsored by 44 professional societies.
      More than 20 countries were represented. EVIDENCE: Literature review, expert
      opinion, and input from an Internet bulletin board were all considered in
      developing recommendations. The strength of evidence of the scientific data was
      considered of paramount importance. CONSENSUS PROCESS: Bethesda 2001 was a year
      long iterative review process. An Internet bulletin board was used for discussion
      of issues and drafts of recommendations. More than 1000 comments were posted to
      the bulletin board over the course of 6 months. The Bethesda Workshop, held April
      30-May 2, 2001, was open to the public. Postworkshop recommendations were posted
      on the bulletin board for a last round of critical review prior to finalizing the
      terminology. CONCLUSIONS: Bethesda 2001 was developed with broad participation in
      the consensus process. The 2001 Bethesda System terminology reflects important
      advances in biological understanding of cervical neoplasia and cervical screening
      technology.

PMID- 11966387
TI  - 2001 Consensus Guidelines for the management of women with cervical cytological
      abnormalities.
AB  - OBJECTIVE: To provide evidence-based consensus guidelines for the management of
      women with cervical cytological abnormalities and cervical cancer precursors.
      PARTICIPANTS: A panel of 121 experts in the diagnosis and management of cervical
      cancer precursors, including representatives from 29 professional organizations,
      federal agencies, and national and international health organizations, were
      invited to participate in a consensus conference sponsored by the American
      Society for Colposcopy and Cervical Pathology (ASCCP). EVIDENCE AND CONSENSUS
      PROCESS: Guidelines for the management of women with cervical cytological
      abnormalities were developed through a multistep process. Starting 6 months
      before the conference, working groups developed draft management guidelines based
      on formal literature reviews of English-language articles published in 1988-2001,
      as well as input from the professional community at large, obtained using
      interactive Internet-based bulletin boards. On September 6-8, 2001, the ASCCP
      Consensus Conference was held in Bethesda, Md. Guidelines with supporting
      evidence were presented and underwent discussion, revision, and voting.
      CONCLUSIONS: Management of women with atypical squamous cells (ASC) depends on
      whether the Papanicolaou test is subcategorized as of undetermined significance
      (ASC-US) or as cannot exclude high-grade squamous intraepithelial lesion (HSIL)
      (ASC-H). Women with ASC-US should be managed using a program of 2 repeat cytology
      tests, immediate colposcopy, or DNA testing for high-risk types of human
      papillomavirus (HPV). Testing for HPV DNA is the preferred approach when liquid
      based cytology is used for screening. In most instances, women with ASC-H, low
      grade squamous intraepithelial lesion, HSIL, and atypical glandular cells should
      be referred for immediate colposcopic evaluation.

PMID- 11966389
TI  - Race/ethnicity and cancer survival: the elusive target of biological differences.

PMID- 11966388
TI  - A 60-year-old woman trying to discontinue hormone replacement therapy.

PMID- 11966390
TI  - New Bethesda terminology and evidence-based management guidelines for cervical
      cytology findings.

PMID- 11966396
TI  - Pharmacogenomics and pharmacogenetics of neurodegenerative diseases: towards new
      targets.

PMID- 11966397
TI  - Human genetic variation.

PMID- 11966398
TI  - Using a systems biological approach to develop novel therapeutics.

PMID- 11966399
TI  - Genome medicine: gene therapy for the millennium.

PMID- 11966400
TI  - The pharmacogenetics of NAT: structural aspects.
AB  - Arylamine N-acetyltransferases (NATs) catalyze the transfer of an acetyl group
      from acetyl-CoA to arylhydrazines and to arylamine drugs and carcinogens or to
      their N-hydroxylated metabolites. NAT plays an important role in detoxification
      and metabolic activation of xenobiotics and was first identified as the enzyme
      responsible for inactivation of the antitubercular drug isoniazid, an
      arylhydrazine. The rate of inactivation was polymorphically distributed in the
      population: the first example of interindividual pharmacogenetic variation.
      Polymorphism in NAT activity is primarily due to single nucleotide polymorphisms
      (SNPs) in the coding region of NAT genes. NAT enzymes are widely distributed in
      eukaryotes and genome sequences have revealed many homologous members of this
      enzyme family in prokaryotes. The structures of S almonella typhimurium and
      Mycobacterium smegmatis NATs have been determined, revealing a unique fold in
      which a catalytic triad (Cys-His-Asp) forms the active site. Determination of
      prokaryotic and eukaryotic NAT structures could lead to a better understanding of
      their role in xenobiotics and endogenous metabolism.

PMID- 11966401
TI  - Functional genomics approaches to understanding brain disorders.
AB  - The completed draft of the human genome sequence has facilitated a revolution in
      neuroscience research. This sequence information and the development of new
      technologies used to analyze gene expression on a genomic scale provides a new
      and powerful means to investigate brain disorders of unknown etiology and to
      isolate novel drug targets for these disorders. The term functional genomics
      broadly describes a set of technologies and strategies directed at the problem of
      determining the function of genes, and understanding how the genome works
      together to generate whole patterns of biological function. The most powerful of
      these functional genomics approaches, expression profiling or DNA microarrays,
      can be used to analyze the expression of thousands of genes simultaneously. The
      results to date from the application of DNA microarray methods to postmortem
      diseased human brain tissue, animal models and cell culture models of brain
      disorders provide an exciting glimpse into the future of this field.

PMID- 11966402
TI  - Candidate gene approach for pharmacogenetic studies.
AB  - Genetic diversity in the form of single nucleotide DNA polymorphisms (SNPs)
      contributes to variable disease susceptibility and drug response. The candidate
      gene approach has been widely used to identify the genetic basis for
      pharmacogenetic traits and becomes increasingly more powerful with the recent
      advances in genomic technologies. High-throughput sequencing and SNP genotyping
      technologies allow the study of thousands of candidate genes and the
      identification of those involved in drug efficacy and toxicity. Expression-based
      genomic technologies such as DNA microarrays and proteomics also facilitate the
      understanding of important biological and pharmacological pathways, thus
      identifying more candidate genes for SNP studies. Candidate gene-based
      pharmacogenetic studies will lead to improved drug development, improved clinical
      trial design and therapeutics tailored to individual genotypes.

PMID- 11966403
TI  - Hypertension, genotype and oral contraceptives.
AB  - Oral contraceptive-induced hypertension (OCIH) is a well-recognized phenomenon
      characterized by an increase in blood pressure levels after beginning
      estroprogestin therapy and a reduction to normal levels within 1 year after
      suspension of the therapy. The pathophysiology of this condition is still not
      understood: several lines of evidence indicate a role for a genetic
      susceptibility to the development of this disease. In this article, the
      epidemiology and the pathogenesis of OCIH are reviewed with particular emphasis
      on the genetic influence in light of the most recent studies in this field.

PMID- 11966404
TI  - Angiotensin II receptor polymorphisms in hypertension. Pharmacogenomic
      considerations.
AB  - Molecular variants of individual components of the renin-angiotensin system (RAS)
      are thought to contribute to inherited predisposition towards essential
      hypertension. Polymorphisms in genes of angiotensinogen (AGT), angiotensin I
      converting enzyme (ACE) and angiotensin II type 1 receptor (AT-1) have been
      related to differential responses to antihypertensive drugs. AT-1 receptor
      mediates the major pressor and trophic actions of angiotensin II (Ang II). At
      least 14 AT-1 polymorphisms have been described in the gene (AGT1R); in
      particular the +1166 A/C polymorphism has been associated with the severe form of
      essential hypertension. A relationship was suggested between this polymorphism
      and the humoral and renal hemodynamic responses to losartan, an antihypertensive
      drug acting as an AT-1 blocker. Variability in the individual response to AT-1
      antagonists could also be due to variations in the pharmacokinetics of the drugs.
      This review presents current knowledge on Ang II-receptors and polymorphisms in
      AGT1R related to cardiovascular disease and antihypertensive therapy.

PMID- 11966405
TI  - Towards the pharmacogenomics of cystic fibrosis.
AB  - Cystic fibrosis (CF) is the most common lethal recessive genetic disease
      affecting children in Europe and the US. CF is a multiorgan disease and may
      present a variety of clinical symptoms, like chronic obstructive lung disease,
      exocrine pancreatic insufficiency (PI) and elevated sweat chloride concentration.
      CF mutations have also been found in other related clinical diseases such as
      congenital bilateral absence of the vas deferens (CBAVD), disseminated
      bronchiectasis and chronic pancreatitis. These clinical overlaps pose
      etiopathogenetic, diagnostic and therapeutic questions. Despite stunning advances
      in genomic technologies and drug discovery, drug therapy often improves disease
      symptoms but does not cure the disease. One of the main causes of this failure in
      CF cure may be attributable to genetic variability and to the scarce knowledge of
      CF biochemistry. Therefore, knowing the genotype of a patient might help improve
      drug efficacy, reduce toxicity and suggests innovative genomic-based therapy
      approaches.

PMID- 11966406
TI  - The thiopurine S-methyltransferase gene locus -- implications for clinical
      pharmacogenomics.
AB  - Thiopurine methyltransferase catalyzes the S-methylation of azathioprine (AZA), 6
      mercapto-purine (6-MP) and thioguanine, medications widely used to treat
      malignancies, rheumatic diseases, dermatologic conditions, inflammatory bowel
      disease and solid organ transplant rejection. TPMT activity exhibits a genetic
      polymorphism in 10% of Caucasians, with 1/300 individuals having complete
      deficiency. Patients with intermediate or deficient TPMT activity are at risk for
      excessive toxicity, including fatal myelosuppression, after receiving standard
      doses of thiopurine medications. The molecular basis for low TPMT activity has
      been elucidated, leading to the development of assays for the three signature
      mutations, which account for the majority of mutant alleles. TPMT genotype is
      correlated with erythrocyte and leukemia blast cell TPMT activity and associated
      with a risk of toxicity after thiopurine therapy. Recent studies defined target
      starting doses for mercaptopurine based on TPMT genotypes. This polymorphism is
      one of the best models for the translation of genomic information to guide
      patient therapeutics.

PMID- 11966407
TI  - Novel insulin sensitizers: pharmacogenomic aspects.
AB  - Thiazolidinediones (TZD, glitazones) are a new class of oral antidiabetic drugs
      which exert their insulin sensitizing action by stimulation of the nuclear
      transcription factor peroxisome proliferator-activated receptor gamma (PPAR
      gamma). At present pioglitazone and rosiglitazone are available for clinical use.
      Different activation levels of PPAR-gamma and of co-factors determine the binding
      of PPAR-gamma to distinct target genes, which in turn regulates their
      transcriptional activity. TZD lower blood glucose levels, partly by influencing
      glucose transporters and the insulin-signaling pathway. In this review the
      molecular and cellular mechanisms as well as the metabolic effects of PPAR
      activation by TZD are discussed. Knowledge regarding the influence of genetic
      variations of PPAR-gamma on the effects of TZD is so far limited to in vitro
      studies. The results of these studies are reviewed.

PMID- 11966408
TI  - Lithium long-term treatment in mood disorders: clinical and genetic predictors.
AB  - Lithium is the most widely used long-term treatment for recurrent mood disorders.
      Despite its proven efficacy, patients show a variable response, ranging from
      complete efficacy to no influence at all. This paper reviews possible predictors
      of response focusing on molecular genetic studies. The functional polymorphism in
      the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has
      been associated with lithium long-term efficacy in two independent studies,
      marginal associations have been reported for tryptophan hydroxylase and inositol
      polyphosphate 1-phosphatase (INPP1). A number of other candidate genes and
      anonymous markers did not yield positive associations. Therefore, even though
      some positive results have been reported, no unequivocal susceptibility gene for
      lithium efficacy has been identified.

PMID- 11966409
TI  - Recent progress in multiple sequence alignment: a survey.
AB  - The assembly of a multiple sequence alignment (MSA) has become one of the most
      common tasks when dealing with sequence analysis. Unfortunately, the wide range
      of available methods and the differences in the results given by these methods
      makes it hard for a non-specialist to decide which program is best suited for a
      given purpose. In this review we briefly describe existing techniques and expose
      the potential strengths and weaknesses of the most widely used multiple alignment
      packages.

PMID- 11966410
TI  - Discovery Partners International.
AB  - Discovery Partners International (Nasdaq: DPII) is a leader in collaborative drug
      discovery. DPI's integrated discovery framework encompasses a broad spectrum of
      capabilities in chemistry, biology, informatics, computational modeling and
      synthesis automation. DPI's approach to drug discovery places a heavy emphasis on
      up-front interdisciplinary analysis of its client's problems. By drawing on the
      collective expertise of its chemists, biologists and computational scientists,
      lead discovery and optimization strategies with the highest likelihood of success
      are formulated and then executed using the company's extensive capabilities and
      high output technology platforms.

PMID- 11966411
TI  - Gentris corporation.
AB  - Gentris Corporation is engaged in the development and rapid commercialization of
      innovative proprietary clinical pharmacogenomic products and services. The
      company provides global pharmaceutical research organizations with turn-key
      pharmacogenomic solutions to improve the efficiency and predictability of drug
      development. The ultimate benefit to these organizations is to shorten drug
      development cycles, improve new drug approval rates and allow marginal drugs to
      advance towards final approval. In the near future, the company will develop
      specialized, high quality, reliable diagnostic products, which will provide
      physicians and their patients with access to pharmacogenomic testing, as
      personalized medicine becomes the new standard of medical practice.

PMID- 11966412
TI  - The rhythms of bereavement.
AB  - This research was conducted to add to the understanding of the experiences of
      elderly, bereaved spouses in the rural South. During this study, data were
      gathered from 29 informants, many of whom were interviewed multiple times over
      several months. Data in the form of field notes and transcribed interviews were
      treated as texts and were subjected to hermeneutic analysis. The results explore
      the rhythm of grief as it is experienced in three stages over the months after a
      death; the rhythmic waves of grief, the cycles of sleeping and wakefulness, and
      the stages of sleep itself; how bereavement is spaced through the life span; and
      the way informants experienced and talked about the duration of their
      bereavement.

PMID- 11966413
TI  - "It ain't necessarily so"... Challenging mainstream thinking about bereavement.
AB  - Traditional theories about grief and bereavement have been fundamentally and
      thoroughly challenged, primarily by Stroebe and Stroebe (1987), Wortman and
      Silver (1989), and Bonanno and Kaltman, (1999). In contrast to the old grief work
      perspective with its working through, depression, social disclosure of distress,
      and termination of the relationship to the dead, a completely different new
      perspective focusing on repression of depressive emotions and thoughts, display
      of positive emotions, moderate social disclosure, and continuation of the
      relationship to the dead has been proposed and scientifically supported. Still,
      the grief work perspective is very popular. In this article, both the old and the
      new views are challenged, and a more moderate perspective is suggested. Rational
      and irrational reasons for the old perspective's popularity are suggested.
      Consequences for therapeutic work (psychotherapy, counseling, nursing) are
      outlined. Finally, it is underlined that grief may be a meaningful, enrichening
      experience.

PMID- 11966414
TI  - Disclosure after a sibling's death from AIDS.
AB  - The purpose of this article was to describe patterns of disclosure among adults
      after their sibling's death from AIDS. A descriptive study design was done by use
      of a cross-sectional sample including 87 adults from separate families. Sibling
      responses were audiotaped and content analyzed. Six categories of disclosure
      emerged from the data: Purposeful, "If Asked I Tell," Selective, Protective,
      Restricted, and Avoidant. Categories differed across three dimensions: usual
      method of telling, goal of method, and underlying belief about public
      disclosures. It was found that siblings disclose variably after their brother's
      or sister's death from AIDS. In bereavement contexts characterized by stigma,
      bereaved siblings consider many potential consequences before choosing how they
      will tell others their brother or sister died from AIDS.

PMID- 11966415
TI  - Children's responses to family member homicide.
AB  - Homicide is a significant behavioral deviation resulting in a sudden and
      unexpected loss of life and can leave children in the chaotic wake. Interviews
      conducted with 13 children ages 9 to 11 years during the initial 1 to 3 months
      after a family homicide provided insight into themes of bereavement. A major
      finding in the study was that the witnessing or hearing the news of a family
      member homicide was a powerful associative factor for childhood posttraumatic
      stress disorder (PTSD) and for complicated bereavement.

PMID- 11966417
TI  - Experiences in family bereavement.
AB  - These case studies illustrate the stories of two families grieving the losses of
      their children. Some 42,000 infants and children die yearly in the United States,
      but there is a dearth of research for professionals to draw on when considering
      the family as the context for grieving the loss of a child. These narratives
      illustrate the identity crisis the family as whole goes through after the death
      of a child-the sense of parental duty, the need for communication, and the goal
      of reunification of the family unit. These stories also provide direction for
      further research with bereaved families.

PMID- 11966416
TI  - No more the same: the lives of adolescents in Taiwan who have lost fathers.
AB  - This article offers a reconstruction of the life worlds of 30 adolescents, aged 9
      to 18, from 20 families who have lost their fathers through death. Through
      interviews designed to measure the impact of culture on adolescent coping, six
      themes on rebuilding their lives, "no more the same," were identified: (1)
      isolation from death, (2) incompleteness, (3) staying inside, (4) worrying with
      mother, (5) building connections with fathers, and (6) restructuring the family.
      By exploring the lives of fatherless adolescents in Taiwan, the findings of this
      study illustrate a metaphor "no more the same" to represent life after father's
      death in such culture.

PMID- 11966419
TI  - A novel approach to combinatorial library design.
AB  - We address the problem of designing a general-purpose combinatorial library to
      screen for pharmaceutical leads. Conventional approaches focus on diversity as
      the primary factor in designing such libraries. We suggest making screening
      libraries out of a set of pharmaceutically relevant scaffolds, with multiple
      analogs per scaffold. The rationale for this rests on the fact that even though
      the hit-rate in active series is much higher than in the database as a whole,
      often a large fraction of the compounds in active series are inactive. This is
      especially true when the series has not been optimized for the target under
      study. We introduce the concept of  hit-rate within a series  and use historic
      screening data to arrive at a crude estimate for it. We then use simple
      probability arguments to show that 50-100 compounds are required in each series
      in order to be nearly certain of finding at least one active compound in each
      true active series for any given target.

PMID- 11966418
TI  - Bereaved parents' use of individual, family, and community resources 4 to 60
      months after a child's violent death.
AB  - We recruited a community-based sample of 261 parents bereaved by the violent
      deaths of their 12- to 28-year-old children. Parents were observed over time, and
      data were collected from several sources. The findings showed that of six
      individual, family, and community resources examined, none of the resources
      seemed to improve parents' outcomes either 1 or 5 years later. Implications of
      the findings are discussed.

PMID- 11966420
TI  - Rational principles of compound selection for combinatorial library design.
AB  - It is practically impossible in a short period of time to synthesize and test all
      compounds in any large exhaustive chemical library. We discuss rational
      approaches to selecting representative subsets of virtual libraries that help
      direct experimental synthetic efforts for both targeted and diverse library
      design. For targeted library design, we consider principles based on the
      similarity to lead molecules. In the case of diverse library design, we discuss
      algorithms aimed at the selection of both diverse and representative subsets of
      the entire chemical library space. We illustrate methodologies with several
      practical examples.

PMID- 11966421
TI  - Optimization of focused chemical libraries using recursive partitioning.
AB  - A number of methods currently exist for designing chemical libraries. General or
      universal libraries use a measurement of chemical diversity in their design and
      seek to cover as much of chemical space as possible in order to maximize the
      likelihood of discovering a novel lead class of active compounds. Focused
      chemical libraries are then synthesized to expand on this particular class and
      thoroughly explore the space about it. Rarely, however, is relevant biological
      data tightly incorporated in the design of focused libraries. Recursive
      partitioning is a statistical technique that is used to quickly build SAR models
      from high-throughput screening data sets and associated chemical descriptors.
      Using these models in a virtual screening mode significantly increases the
      probability of finding other active compounds. The predicted activity can be also
      be used as the fitness function for a genetic algorithm that is designed to
      select monomer subsets having a higher probability of being active. This
      dramatically reduces the number of compounds that need to be synthesized in
      focused libraries thus saving considerable time, effort and expense. This paper
      describes how recursive partitioning models are used to optimize the design of
      focused chemical libraries.

PMID- 11966422
TI  - A probabilistic approach to high throughput drug discovery.
AB  - A methodology is presented in which high throughput screening experimental data
      are used to construct a probabilistic QSAR model which is subsequently used to
      select building blocks for a virtual combinatorial library. The methodology is
      based upon statistical probability estimation and not regression. The methodology
      is applied to the construction of two focused virtual combinatorial libraries:
      one for cyclic GMP phosphodiesterase type V inhibitors and one for acyl
      CoA:cholesterol O-acyltransferase inhibitors. The results suggest that the
      methodology is capable of selecting combinatorial substituents that lead to
      active compounds starting with binary (pass/fail) activity measurements.

PMID- 11966423
TI  - Testing non-additivity of biological activity in a combinatorial library.
AB  - Combinatorial chemistry offers new opportunities to generate and analyze QSAR
      data. Traditional QSAR attempts to correlate activity with structure. With
      combinatorial chemistry, it is possible to correlate activity directly with the
      reagents used in a combinatorial library. If one can determine which reagents
      lead to the compounds of highest activities, it may then be possible to predict
      active compounds in virtual libraries of 10(6) to 10(10) compounds. This would
      greatly facilitate library design and provide confidence that the best compounds
      are being considered for synthesis. An important question is whether the activity
      of a product molecule can be considered as a sum of its components. This is
      referred to as additivity between reagents. If there is non-additivity, it is
      necessary to identify and include the non-additive terms in the model in order to
      improve QSAR models. Presented here are methods for developing QSAR models
      relating compound activity to reagents and a method for detecting the second
      effects of side-chain non-additivity. If the reagents in a library are shown to
      be additive in their contribution to activity, simple QSAR based on additive
      models can be applied confidently to reagents. Testing non-additivity can also
      guide the synthesis of the library. If the contributions are shown to be additive
      then the strategy for library synthesis may be shifted to include many reagents
      of a given type but not to make all combinations. The result is more efficient
      use of resources. In the analysis of percent inhibition data of a combinatorial
      library an additive model using reagents as descriptors yields a R(2) of 0.43.
      Application of this method is probably appropriate for HTS single point data
      while methods employing topological or pharmacophore based descriptors would be
      necessary to adequately model IC50 data.

PMID- 11966424
TI  - Grouping of coefficients for the calculation of inter-molecular similarity and
      dissimilarity using 2D fragment bit-strings.
AB  - This paper compares 22 different similarity coefficients when they are used for
      searching databases of 2D fragment bit-strings. Experiments with the National
      Cancer Institute s AIDS and IDAlert databases show that the coefficients fall
      into several well-marked clusters, in which the members of a cluster will produce
      comparable rankings of a set of molecules. These clusters provide a basis for
      selecting combinations of coefficients for use in data fusion experiments. The
      results of these experiments provide a simple way of increasing the effectiveness
      of fragment-based similarity searching systems.

PMID- 11966425
TI  - Scalable methods for the construction and analysis of virtual combinatorial
      libraries.
AB  - One can distinguish between two kinds of virtual combinatorial libraries:  viable
      and  accessible . Viable libraries are relatively small in size, are assembled
      from readily available reagents that have been filtered by the medicinal chemist,
      and often have a physical counterpart. Conversely, accessible libraries can
      encompass millions or billions of structures, typically include all possible
      reagents that are in principle compatible with a particular reaction scheme, and
      they can never be physically synthesized in their entirety. Although the analysis
      of viable virtual libraries is relatively straightforward, the handling of large
      accessible libraries requires methods that scale well with respect to library
      size. In this work, we present novel, efficient and scalable techniques for the
      construction, analysis, and in silico screening of massive virtual combinatorial
      libraries.

PMID- 11966426
TI  - High-throughput chemistry toward complex carbohydrates and carbohydrate-like
      compounds.
AB  - In the area of peptide and nucleic acid chemistry and biology, high-throughput
      synthesis has played an important role in providing useful small-molecule-based
      chemical probes in understanding the structure and function relationships. The
      past several years, there has been a constant rise in interest toward
      understanding the biological roles and functions of another important class of
      biomolecules, i.e., carbohydrates and carbohydrate conjugates. Although at early
      stages, in recent years, several groups have developed high-throughput synthetic
      methods to obtain complex carbohydrates or carbohydrate-like small-molecules. The
      present review article summarizes some of these developments.

PMID- 11966427
TI  - Synthesis of trifluoromethyl ketones using polymer-supported reagents.
AB  - A two step synthesis of trifluoromethyl ketones from aldehydes is reported. A
      combination of polymer-supported reagents and sequestering agents were employed
      to effect the transformation without the need for chromatographic purification.

PMID- 11966428
TI  - Optimisation of polystyrene resin-supported Pt catalysts in room temperature,
      solvent-less, oct-l-ene hydrosilylation using methyldichlorosilane.
AB  - Six precursor resins with systematic variation of porous parameters were prepared
      by suspension polymerisation using specific compositions of divinylbenzene,
      styrene vinylbenzyl chloride (VBC) and 2-ethylhexan-l-ol (a porogen). Surface
      areas from N(2) sorption and BET analysis were approximately 2-170 m(2)g-(1). The
      VBC content in each case was 38 mol% and these groups were aminated using the
      sodium salt of trimethylethylene diamine. Pt was introduced onto each resin at
      three different loadings (approximately 0.03, approximately 0.2 and approximately
      0.4 mmol g-(1)) by appropriate manipulation of K(2)PtCl(6). The matrix of 18
      resin-supported Pt complexes was then assessed for catalytic activity in the room
      temperature, solvent-less, hydrosilylation of oct-l-ene using
      methyldichlorosilane such that alkene: silane: Pt ratio was fixed at 2:1:1x10(
      3). Though all the catalysts showed activity lower than that of homogeneous
      Speier s catalyst, most were sufficiently active to be potentially valuable
      heterogeneous catalysts in the laboratory, and indeed the plant. The most lightly
      loaded resins proved to be the least active. The remainder were recycled 5 times,
      and the best performers, the most highly loaded species, a further 5 times making
      10 consecutive uses in all. A strong dependence on the porous structure of the
      resins was demonstrated with the activity rising systemically with the surface
      area. The two highest surface area highest loaded species displayed good activity
      even when used for the tenth time. The level of concurrent alkene isomerisation
      observed was very low throughout (<1%) making these heterogeneous species very
      selective as well as highly active. Overall the derived catalysts are excellent
      candidates for use in the research laboratory, and with further development could
      also be valuable in continuous processes.

PMID- 11966429
TI  - The use of a supported base and strong cation exchange (SCX) chromatography to
      prepare a variety of structurally-diverse molecular libraries prepared by
      solution-phase methods.
AB  - The preparation of molecular libraries of aminomethylbiaryls, allylic amines, and
      ethanolamines using solution-phase methodology is described. In particular, the
      use of a solid-supported base reagent (PTBD resin) and strong cation
      exchange(SCX) resin to effect 'catch and release' purification across these
      diverse libraries is highlighted.

PMID- 11966430
TI  - Parallel synthesis of tri- and tetrasubstituted ureas from carbamoyl imidazolium
      salts.
AB  - A method for producing tri- and tetrasubstituted ureas from carbamoyl imidazolium
      salts is presented. Carbamoyl imidazolium salts are prepared from the reaction of
      N,N  carbonyldiimidazole (CDI) with secondary amines, followed by alkylation with
      iodomethane. These stable salts can be stored for extended periods and are
      effective electrophilic carbamoylation reagents. Primary and secondary amines add
      to carbamoyl imidazolium salts at room temperature to give tri- and
      tetrasubstituted ureas in excellent yields. This reaction was used to synthesize
      ureas using both liquid-liquid extraction and solid-phase extraction (cation
      exchange) purification techniques. Liquid-liquid extraction affords the product
      ureas more cleanly than cationic exchange. A series of urea compounds were
      synthesized using parallel synthesis techniques in high yields and with suitable
      purity for routine in vitro biological tests. These studies validate the utility
      of carbamoyl imidazolium salts as useful  building blocks  for combinatorial
      library synthesis.

PMID- 11966431
TI  - Developing soluble polymers for high-throughput synthetic chemistry.
AB  - Soluble polymers have emerged as viable alternatives to resin supports across the
      broad spectrum of high-throughput organic chemistry. As the application of these
      supports become more widespread, issues such as broad-spectrum solubility and
      loading are becoming limiting factors and therefore new polymers are required to
      overcome such limitations. This article details the approach made within our
      group to new soluble polymer supports and specifically focuses on parallel
      libraries of block copolymers, de novo poly(styrene-co-chloromethylstyrene), PEG-
      stealth  stars, and substituted poly(norbornylene)s.

PMID- 11966433
TI  - Automated parallel solid-phase synthesis of non-peptide CCR1 receptor
      antagonists.
AB  - An automated, parallel, solid-phase synthesis and screening strategy using
      commercially available aryl acetic acids as starting materials has discovered
      novel, non-peptide CCR1 antagonists (K(i) < 100 nM).

PMID- 11966432
TI  - Synthesis of combinatorial libraries based on terpenoid scaffolds.
AB  - Triterpenoid-based scaffolds betulinic acid (1a) and ursolic acid (1b), have been
      used for the generation of combinatorial libraries in parallel format using solid
      phase organic synthesis method. These templates have the potential for the
      synthesis and amplification of triterpenoid-based compounds with one and two
      point diversity. This has been demonstrated by the synthesis of two small
      libraries comprising 18 derivatives each of betulinic acid and ursolic acid with
      structural diversity at C-3 and C-28 positions. The primary screening of
      antimalarial activity of these libraries against P. falciparum in vitro led to
      the identification of four compounds with 5 fold increase in the activity
      compared to betulinic and ursolic acids.

PMID- 11966434
TI  - Parallel synthesis of PNA-peptide conjugate libraries.
AB  - An optimized semi-automatic protocol for parallel synthesis of up to 96 peptide
      nucleic acids (PNA) or PNA-peptide conjugates using Boc-protection strategy has
      been developed using a robotic system. The approach is illustrated by
      synthesizing PNA and PNA-peptide libraries varying between 15 and 27  amino acid 
      units. The peptides (NLS (nuclear localization signal) or Tat-peptide) were
      attached to N-terminus of the PNA. The method was found to be far superior to
      that based on the SPOT/Fmoc protocol by which PNA oligomers are synthesized on a
      modified cellulose membrane. On a 0.5 micromole scale the method typically
      yielded 2 mg product of 90% purity by HPLC/MALDI-TOF analysis. This approach is
      suitable for screening of a large number of PNA and/or peptide sequences for
      biochemical and biological studies.

PMID- 11966435
TI  - Chemical synthesis of benzamide riboside.
AB  - The C-glycosidic nicotinamide riboside analogue (1) was prepared by reaction of
      ribonolactone 16 with the lithiated 2-oxazoline 13 followed by triethylsilane
      reduction of the hemiacetal 17 to the tetrahydrofurane 18. Cleavage of the
      oxazoline group in 20 to the acid 21, conversion of the acid chloride 22 to the
      amide 23, and hydrogenative debenzylation afforded the benzamide riboside 1.
      Phosphorylation of the acetonide 26 and acid-catalyzed cleavage of the resulting
      ketal yielded the pseudonucleotide 27.

PMID- 11966436
TI  - The chemistry of nicotinamide adenine dinucleotide (NAD) analogues containing C
      nucleosides related to nicotinamide riboside.
AB  - Oncolytic C-nucleosides, tiazofurin (2-beta-D-ribofuranosylthiazole-4
      carboxamide) and benzamide riboside (3-beta-D-ribofuranosylbenzamide) are
      converted in cell into active metabolites thiazole-4-carboxamide- and benzamide
      adenine dinucleotide, TAD and BAD, respectively. TAD and BAD as NAD analogues
      were found to bind at the nicotinamide adenine dinucleotide (cofactor NAD) site
      of inosine monophosphate dehydrogenase (IMPDH), an important target in cancer
      treatment. The synthesis and evaluation of anticancer activity of a number of C
      nucleosides related to tiazofurin and nicotinamide riboside then followed and are
      reviewed herein. Interestingly, pyridine C-nucleosides (such as C-nicotinamide
      riboside) are not metabolized into the corresponding NAD analogues in cell. Their
      conversion by chemical methods is described. As dinucleotides these compounds
      show inhibition of IMPDH in low micromolar level. Also, the synthesis of BAD in
      metabolically stable bis(phosphonate) form is discussed indicating the usefulness
      of such preformed inhibitors in drug development. Among tiazofurin analogues,
      Franchetti and Grifantini found, that the replacement of the sulfur by oxygen (as
      in oxazafurin) but not the removal of nitrogen (tiophenfurin) of the thiazole
      ring resulted in inactive compounds. The anti cancer activity of their synthetic
      dinucleotide analogues indicate that inactive compounds are not only poorly
      metabolized in cell but also are weak inhibitors of IMPDH as dinucleotides.

PMID- 11966437
TI  - Studies on the mechanism of action of benzamide riboside: a novel inhibitor of
      IMP dehydrogenase.
AB  - Benzamide is a well known inhibitor of poly(ADP-ribose)polymerase, an enzyme
      involved in DNA repair. However, benzamide exhibited neuotoxicity in animals and
      hence, in the hope of overcoming this problem, benzamide riboside (BR) was
      synthesized. Our mechanism of action studies on BR suggested that the agent was
      being metabolized to its 5'-monophosphate and then to its NAD analogue (BAD,
      benzamide adenine dinucleotide) that inhibits Inosine 5'-monophosphate
      dehydrogenase (IMPDH). IMPDH is the rate-limiting enzyme of the branched purine
      nucleotide synthetic pathway that provides guanylates including GTP and dGTP.
      There are two isoforms of IMPDH, type I that is constitutively present in all
      cells, and type II that is inducible and is present in highly proliferating cells
      such as cancer. Ongoing studies with BR analogues suggest that they are more
      selective in inhibiting IMPDH type II. Our studies have characterized the
      metabolites of BR, especially its NAD analogue, BAD, by synthesizing this active
      metabolite by enzymatic means, and identifying its structure by NMR and mass
      spectrometry. We have partially purified IMPDH from tumor cells and have examined
      the kinetics of inhibition of IMPDH by BAD. We have also compared biochemical and
      cytotoxic activities of BR with tiazofurin and selenazofurin, that share similar
      mechanisms of action with BR. Our studies demonstrated that 2-3-fold more BAD is
      formed compared to TAD and SAD, the active metabolites of tiazofurin and
      selenazofurin, respectively. BR has demonstrated potent cytotoxic activity in a
      diverse group of human tumor cells, specifically more active in sarcomas and CNS
      neoplasms compared to tiazofurin or selenazofurin. Future in vivo animal studies
      should set a stage for determining its effectiveness in clinical Phase I studies.

PMID- 11966438
TI  - Modulation of cytotoxicity of benzamide riboside by expression of NMN
      adenylyltransferase.
AB  - Benzamide riboside (BR) is a nucleoside prodrug that is phosphorylated to its 5'
      monophosphate (BRMP) and then converted to its active metabolite, BAD (benzamide
      adenine dinucleotide), an analogue of NAD by the action of NMN
      adenylyltransferase (NMNAT). BAD is a potent, reversible, and noncompetitive
      inhibitor of inosine 5'-monophosphate dehydrogenase (IMPDH) resulting in
      depletion of guanylates (GTP and dGTP). IMPDH inhibitors such as BR induce
      differentiation and apoptosis as a consequence of GTP depletion. Tiazofurin (TR)
      and selenazofurin (SR) require similar metabolism by NMNAT. NMNAT is the rate
      limiting step in the synthesis of NAD and NAD analogues. BR- and TR-sensitive
      leukemic cells contain high NMNAT activity, whereas resistant clones have greatly
      downregulated NMNAT activity (<0.1% of wild type). Perhaps the applicability of
      BR and analogues could be enhanced if combined with NMNAT gene expression in BR
      resistant leukemic blasts. NAD has important regulatory role in repair of DNA
      damage and cell growth since it is a substrate for poly(ADP-ribose) polymerase
      (PARP). PARP appears to direct short-patch base excision repair and induce p53
      upregulation leading to apoptosis. BR inhibits PARP at high concentrations when
      assayed in permeabilized leukemic cells. Several other IMPDH inhibitors (TR,
      mycophenolic acid, and ribavirin) exhibit similar PARP inhibitory activity.
      Although this inhibition was reversible, it was not prevented by the addition of
      guanosine, GTP, or its nonhydrolyzable analog gamma-S-GTP. Therefore, it can be
      concluded that IMPDH inhibitors directly inhibit PARP. Presumably, the shared IMP
      NAD active site of IMPDH has a similar architecture to the NAD-binding pocket of
      PARP.

PMID- 11966439
TI  - Benzamide riboside, a recent inhibitor of inosine 5'-monophosphate dehydrogenase
      induces transferrin receptors in cancer cells.
AB  - Benzamide riboside, a recently discovered inhibitor of IMP dehydrogenase (IMPDH)
      exhibits oncolytic activity. IMPDH is the key enzyme of de novo guanylate
      biosynthesis and was shown to be linked with proliferation. Therefore, IMPDH is a
      very good target for antitumor therapy. In order to be active, benzamide riboside
      has to be converted to BAD, an NAD analogue that binds to the NAD site on IMPDH.
      Inhibition of the enzyme by benzamide riboside selectively inhibits tumor cell
      growth and induces apoptosis in various human tumor cell lines. In this
      manuscript we describe the induction of the CD71 transferrin receptor in human
      promyelocytic leukemia HL-60 cells following treatment with benzamide riboside.
      The results indicate a possible involvement of the iron metabolism in the action
      of this new compound. Benzamide riboside might be clinically used in the
      treatment of leukemia and solid tumors, alone or as part of combination therapy.
      Since transferrin receptors are overexpressed in certain cancers, such as glioma
      and colon cancer, a combination therapy that includes benzamide riboside in
      transferrin-coupled liposomes will not only target cancer cells but also leads to
      suicidal action because benzamide riboside will upregulate transferrin receptors
      on cancer cells thereby make it accessible to dose-intensive chemotherapy. We
      therefore believe that benzamide riboside itself or derivatives of benzamide
      riboside might become an important addition for the treatment to diseases that
      are otherwise fatal.

PMID- 11966440
TI  - Potential mechanisms of benzamide riboside mediated cell death.
AB  - Benzamide riboside (BR) after anabolism to an analogue of NAD, was shown to
      inhibit the activity of NAD-dependent enzymes such as inosine 5'-monophosphate
      dehydrogenase (IMPDH), the rate limiting enzyme in de novo guanylate
      biosynthesis, and malate dehydrogenase which is involved in the citric cycle and
      respiratory chain. BR exhibits strong anti-carcinogenic effects due to growth
      retardation and due to induction of apoptosis and necrosis. Apoptosis is ascribed
      to the inhibition of IMPDH because cell death can be blocked by restoring
      intracellular guanylate metabolism by the addition of guanosine. It is shown
      here, however, that also survival-relevant genes such as cdc25A, akt, bcl-2 and
      transferrin receptor become repressed by BR, whereas the expression level of the
      apoptosis enforcing gene c-myc persists. Even though BR-mediated growth
      retardation still allows BR to induce apoptosis, rapamycin-mediated cell cycle
      block and cell contact inhibition prevent cell death, it strongly suggests that
      BR induces a type of c-Myc-dependent apoptosis. At high concentrations BR induces
      DNA double strand breaks by yet to be determined mechanisms that occur hours
      before necrosis can be detected. This is accompanied by a dramatic decrease of
      intracellular ATP. The artificial restoration of ATP by addition of adenosine or
      sufficient provision of an energy source such as glucose prevents BR-promoted
      necrosis and favors apoptosis. This observation may be of clinical relevance.

PMID- 11966441
TI  - Antitumor activity of benzamide riboside in vitro and in vivo.
AB  - Benzamide riboside (BR), a recent synthetic nucleoside analogue, is a new
      compound demonstrating potent cytotoxic activity in malignant cell lines in vitro
      and in vivo in L1210 leukemia. It exhibits at least two different mechanisms of
      action. These are, first, the inhibition of inosine 5'-monophosphate
      dehydrogenase (IMPDH, EC 1.1.1.205), a rate-limiting enzyme for GTP and dGTP
      synthesis that plays a major role in DNA synthesis, cell proliferation and
      regulation; and second, the induction of apoptosis. Some aspects of BR activity
      in malignant cells in vitro and in vivo are reviewed as well as some of the
      mechanisms behind BR's anti-neoplastic effect.

PMID- 11966442
TI  - Metabolism of the novel IMP dehydrogenase inhibitor benzamide riboside.
AB  - Benzamide riboside (BR) is a novel anticancer agent exhibiting pronounced
      activity against several human tumor cell lines via the inhibition of inosine 5'
      monophosphate dehydrogenase (IMPDH) that catalyzes the formation of xanthine 5'
      monophosphate from inosine 5'-monophosphate and nicotinamide adenine
      dinucleotide, thereby restricting the biosynthesis of guanylates. Phosphorylation
      of BR to its 5'-monophosphate derivative appears to be ubiquitous in most cells
      catalyzed by the enzymes, adenosine kinase, nicotinamide nucleoside kinase and 5'
      nucleotidase. BR 5'-monophosphate is then converted to the active metabolite
      benzamide adenine dinucleotide (BAD) by NMN adenylyltransferase, the rate
      limiting enzyme in the biosynthesis of NAD. As BAD is more potent in the
      inhibition of IMPDH than BR and BR 5'-monophosphate, cytotoxicity of BR is
      closely connected with intercellular metabolism to BAD. However, intracellular
      BAD level is also affected by BADase activity, a phosphodiesterase which
      hydrolyzes BAD to BR-5'-monophosphate and AMP. A recent study demonstrates
      enzymatic deamination of BR to non-cytotoxic benzene carboxylic acid (BR-COOH) as
      the main hepatic BR biotransformation product in rat liver. As the IMPDH
      inhibitors tiazofurin and ribavirin exhibit predominant accumulation and
      biotransformation in liver, hepatic metabolism may be an important factor also
      for BR activation and inactivation and should be considered in human liver during
      cancer therapy when BR is used as a single drug or in combination with other
      anticancer agents.

PMID- 11966443
TI  - Toxicity and efficacy of benzamide riboside in cancer chemotherapy models.
AB  - Benzamide riboside (BR), a synthetic C-nucleoside, acts as a strong growth
      inhibitor of cancer cells in vitro and in vivo. BR, like TR and related
      nucleoside prodrugs, act by anabolism to NAD analogs. These analogs selectively
      inhibit IMPDH, leading to depletion of cellular GTP, growth cessation, and cell
      differentiation. To date only preclinical studies have been carried out. However,
      in tiazofurin (TR), a related drug, phase I/II clinical trials have been
      conducted in patients with acute leukemia and shown to be a very promising agent
      with a response rate of 85% in 26 patients in one of the trials. Tiazofurin is
      now undergoing phase III clinical trials as a result. Dose limiting toxicity of
      tiazofurin was headache, somnolence and nausea with no myelosuppression noted. By
      contrast, BR showed skeletal muscle toxicity, hepatotoxicity and myelosuppression
      in preclinical data. Skeletal muscle toxicity was noted in the paraspinal muscles
      and may represent dose-limiting toxicity. Since BR does exhibit myelosuppression,
      the most common chemotherapy-related side effect in humans, careful judgment is
      warranted should BR be included in multidrug regimens, although BR's potent
      cytotoxicity to tumor cells in preclinical models still makes it a promising
      drug.

PMID- 11966444
TI  - Noninvasive genotyping of dopamine receptor D4 (DRD4) using nanograms of DNA from
      substance-dependent patients.
AB  - A noninvasive DNA sampling method has been implemented collecting buccal mucosa
      cells by cotton wool swabs. An amount of 0.2 2 microg DNA per patient was
      obtained after the phenol-extraction procedure and 0.2 2 ng DNA template was
      sufficient for PCR amplification of the polymorphic 48 basepair repeat region of
      dopamine receptor D4 (DRD4) gene. PCR products were visualized during
      microfabricated electrophoretic separation by laser-induced fluorescent detection
      and automatic data registration. Initial data of genotyping drug-dependent
      subjects shows a relatively high ratio of heterozygotes, possessing either longer
      or shorter variants beside the common 4-repeat DRD4 allele.

PMID- 11966445
TI  - Serotonin reuptake inhibition: an update on current research strategies.
AB  - Selective Serotonin reuptake inhibitors (SSRIs) have contributed to the major
      advances in the treatment of depression and other psychiatric diseases. This
      review summarises current knowledge concerning the SSRI class of drugs and
      discusses the importance of secondary pharmacology in the mechanism of action and
      effectiveness of these drugs. Particular attention is given to the emerging
      importance of the SSRI  plus  approach: where the serotonin reuptake receptor
      inhibition of a drug is supplemented by one or more other receptor interactions
      either by the same drug or by a combination therapy. This area of research has
      shed light on the pharmacological mechanisms of SSRI therapy and has the
      therapeutic usefulness of serotonin reuptake inhibition, especially in the area
      of depression. There are many new emerging SSRI  plus  drugs, which address the
      pharmacological and pharmacokinetic issues of current therapies and these, are
      discussed in detail.

PMID- 11966446
TI  - Beta-amino acids: versatile peptidomimetics.
AB  - The use of peptidomimetics has emerged as a powerful means for overcoming the
      limitations inherent in the physical characteristics of peptides thus improving
      their therapeutic potential. A peptidomimetic approach that has emerged in recent
      years with significant potential, is the use of beta-amino acids. Beta-amino
      acids are similar to alpha-amino acids in that they contain an amino terminus and
      a carboxyl terminus. However, in beta-amino acids two carbon atoms separate these
      functional termini. beta-amino acids, with a specific side chain, can exist as
      the R or S isomers at either the alpha (C2) carbon or the beta (C3) carbon. This
      results in a total of 4 possible diastereoisomers for any given side chain. The
      flexibility to generate a vast range of stereo- and regioisomers, together with
      the possibility of disubstitution, significantly expands the structural diversity
      of beta-amino acids thereby providing enormous scope for molecular design. The
      incorporation of beta-amino acids has been successful in creating peptidomimetics
      that not only have potent biological activity, but are also resistant to
      proteolysis. This article reviews the rapidly expanding applications of beta
      amino acids in the design of bioactive peptide analogues ranging from receptor
      agonists and antagonists, MHC-binding peptides, antimicrobial peptides and
      peptidase inhibitors. Given their structural diversity taken together with the
      ease of synthesis and incorporation into peptide sequences using standard solid
      phase peptide synthesis techniques, beta-amino acids have the potential to form a
      new platform technology for peptidomimetic design and synthesis.

PMID- 11966447
TI  - Nephrotoxins: widespread role of oxidative stress and electron transfer.
AB  - Kidney toxicity comprises an important type of hospital admission with associated
      high costs. Large numbers of chemicals are involved comprising a wide variety of
      classes, both organic and inorganic. These include therapeutic drugs,
      radiocontrast agents, carcinogens, metals, abused drugs, and industrial
      chemicals. This review provides extensive evidence for participation of oxidative
      stress (OS) and electron transfer (ET) as a unifying framework. Application is
      made to all the main classes of nephrotoxins, in addition to many miscellaneous
      types. We believe it is not coincidental that the vast majority of these
      substances incorporate ET functionalities (quinone, metal complex, ArNO2, or
      conjugated iminium) either per se or in metabolites, potentially giving rise to
      reactive oxygen species (ROS) by redox cycling. Some categories, e.g., radiation,
      radiocontrast agents, and peroxides, appear to generate OS by non-ET routes. For
      completeness, other theories are also addressed; a multifaceted approach appears
      the most logical. The ET-OS viewpoint should increase understanding and
      contribute to prevention, e.g., use of antioxidants.

PMID- 11966448
TI  - Selective PGHS-2 inhibitors: a rational approach for treatment of the
      inflammation.
AB  - Prostaglandin-H synthase exists in two isoforms, PGHS-1 and PGHS-2. PGHS-1 is
      present and is constitutively expressed in most cells and tissues, whereas PGHS-2
      is mainly thought to mediate inflammation. Selective prostaglandin-H synthase-2
      (or cyclooxygenase-2) inhibitors have been shown to be potent antiinflammatory
      agents with fewer side effects than currently marketed nonsteroidal
      antiinflammatory drugs (NSAIDs). This review addresses the main classes of the
      selective PGHS-2 inhibitors whose selectivity is documented by supporting PGHS-1
      and PGHS-2 enzyme data. In addition, we also describe our experience in design,
      synthesis and pharmacological in vivo evaluation of new 1,2-benzodioxole
      derivatives as candidate of the selective PGHS-2 inhibitors, with special
      attention to molecular dynamics simulations of these derivatives attached to the
      active site of PGHS-2.

PMID- 11966450
TI  - Vinorelbine in the treatment of non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) remains a fatal disease: the majority of
      patients are diagnosed as having metastases or advanced inoperable tumors. The
      activity of chemotherapy in NSCLC patients is low with objective response rarely
      complete and sustained. Cisplatin-based combinations are considered as the
      standard chemotherapy treatment. Recently., the introduction of new and less
      toxic chemotherapeutic agents., such as vinorelbine., has led investigators to
      research for active non-cisplatin-containing combinations to treat patients with
      advanced disease having as primary needs symptom relief and an acceptable quality
      of life. This review will focus on the pharmacological properties of vinorelbine
      and its role in adjuvant chemotherapy., in combined chemo-radiotherapy., in
      advanced disease and in the particular setting of the elderly. The oral use of
      vinorelbine will be among the future developments of this drug.

PMID- 11966449
TI  - Docetaxel (taxotere) in the treatment of non-small cell lung cancer.
AB  - Docetaxel is a new semi-synthetic anticancer agent derived from bacatin III of
      the needles of the European yew Taxus baccata. Docetaxel has a novel mechanism of
      action since it binds to tubulin inducing its polymerization and promoting stable
      microtubule formation. Several differences exist between docetaxel and
      paclitaxel: (i) broader activity of docetaxel against freshly explanted human
      tumors than paclitaxel; (ii) a 2-fold higher affinity than paclitaxel; (iii) 2.5
      fold more potent than paclitaxel as an inhibitor of cell replication and (iv)
      docetaxel acts at the S-phase whereas paclitaxel at the G(2)/M phases of the cell
      cycle. Preclinical and phase II studies revealed that docetaxel is active against
      NSCLC. In chemotherapy-na ve patients with NSCLC response rates ranged from 19%
      to 54% with a median duration of survival ranging from 6.3 months to 11 months,
      and 1-year survival ranging from 21% to 71%. Docetaxel as single agent provided a
      survival as well as a clinical benefit over BSC in untreated patients with NSCLC.
      Docetaxel has been efficiently combined with cisplatin (ORR 33%-46%), carboplatin
      (ORR 30%-48%), vinorelbine (ORR 20%-51%), gemcitabine (ORR 37%-47%), with a
      median survival ranging from 5-14 months. A preliminary analysis of a multicenter
      randomized trial comparing docetaxel/CDDP with docetaxel/gemcitabine revealed
      that the two regimens had comparable activity in terms, of response rates,
      duration of response, TTP and overall survival; however, the
      docetaxel/gemcitabine combination has a most favourable toxicity profile compared
      to docetaxel/CDDP. Docetaxel has also demonstrated radiosensitizing properties
      and encouraging results have been achieved in combination with irradiation.
      Finally, docetaxel has shown an important activity in previously-treated patients
      with NSCLC with ORR ranging from 16% to 25% with a median survival ranging from
      7.2 months to 10.5 months. Randomized trials revealed that second-line docetaxel
      confers a survival benefit over either BSC or ifosfamide/vinorelbine in
      pretreated patients with NSCLC.

PMID- 11966451
TI  - Neoadjuvant chemotherapy in non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is a systemic illness. More than half of those
      patients who present with stage I-IIIA disease and are resected will experience
      distant relapse. Postoperative adjuvant chemotherapy has been evaluated in
      several randomized trials but the results of these trials have been inconclusive
      with increased survival reported in few trials. In resectable stage IIIA NSCLC
      the findings of three randomized trials have indicated that the survival of these
      patients is better with neoadjuvant chemotherapy plus surgical resection than
      with resection alone. Phase II trials using preoperative concurrent
      chemoradiotherapy have been carried out with encouraging results. The majority of
      patients with stage IIIA NSCLC require multimodality therapy if they are to
      achieve a 5-year survival. Combined modality treatment in locally advanced NSCLC
      continues to evolve and is a subject of ongoing research. One focus for present
      research is to integrate new active agents into the neoadjuvant setting. Another
      challenge is to find better treatment approaches in earlier stages of disease.
      Some data suggest that induction chemotherapy in stage I-II is feasible, does not
      appear to compromise surgery and yields high response rates. A further aim is to
      use molecular biological markers of malignancy to identify patients at highest
      risk of metastatic relapse.

PMID- 11966452
TI  - Comparative evaluation of L-Fd4C and related nucleoside analogs as promising
      antiviral agents.
AB  - As documented in the recent literature, there are more than 50 million people
      infected with HIV worldwide to date since the emergence of HIV and AIDS in the
      Western world in 1981. More importantly, about 7000 people die of AIDS daily with
      2.5 and 2.6 millions total deaths in 1998 and 1999, respectively. On the other
      hand, human hepatitis B virus (HBV) is the leading cause of chronic hepatitis in
      the world. According to WHO executive summary, over 350 millions (approximately
      5% of the world s population) people are chronically infected with HBV. There are
      about 1 million chronic HBV carriers in the United States. Although safe and
      effective vaccination for HBV is available for developing countries, there is
      still no effective treatment for the millions of chronically infected
      individuals. Consequently, long term infection with chronic HBV could lead to
      cirrhosis, and hepatocellular carcinoma. In light of these facts, it is evident
      that the discovery and development of novel antiviral agents for the treatment of
      HIV and HBV is an extremely important undertaking.The interest in L-nucleosides
      was spurred in recent years by the findings that L-nucleosides are generally
      endowed with lower host toxicity while maintaining good antiviral activity in
      comparison to their respective D-nucleosides. The recent FDA approval of
      Lamivudine [L-BCH 189 (3TC)] for the treatment of HIV and HBV further supports
      these notions. Since the discovery of Lamivudine, a large number of 2 ,3 -dideoxy
      (dd)- and 2 ,3 -didehydro-2 ,3 -dideoxy (D4)-L-nucleoside analogs have been
      synthesized and evaluated in hopes of identifying even better antiviral agents.
      As a result, 2 ,3 -Dideoxy-2 ,3 -didehydro-beta-L-fluorocytidine (beta-L-Fd4C)
      was found to be a promising new lead. The first synthesis and antiviral activity
      assessment of L-Fd4C were reported by Lin and Cheng et al. in 1996. Recent
      disclosures from several laboratories clearly demonstrated that L-Fd4C was the
      most potent anti-HBV agent reported to date (vs. 3TC, L-FddC, L-FMAU, etc.). In
      fact, L-Fd4C proved to be at least 10 times more potent than Lamivudine on HBV
      DNA synthesis in the hepatoma cell line HepG2 2.2.15. Compared with L-Fd4C, D
      Fd4C showed similar anti-HIV activity yet reduced anti-HBV activity. 2 F-L-Fd4C
      exhibited excellent acid stability but reduced antiviral activity and
      cytotoxicity. Although L-Fd4C is converted intracellularly by cytoplasmic
      deoxycytidine kinase to its mono-, di- and triphosphate metabolites,43 the newly
      prepared bis(SATE)-L-Fd4CMP proved to be more potent against HBV yet less
      cytotoxic than L-Fd4C itself. The chemically synthesized L-Fd4CTP was found to be
      a poor substrate for human polymerase gamma. A recent report from Zhu and Cheng
      et al. indicated that L-Fd4C had no inhibitory effect on mitochondrial DNA
      synthesis at concentrations up to 10 microM. An in vivo study involving HBV
      infected ducks showed that longer administration of L-Fd4C induced a sustained
      suppression of viremia (>95%) and of viral DNA synthesis in the liver. The same
      study also demonstrated that L-Fd4C is more potent than 3TC in vivo. In summary,
      on the basis of the data presented in this chapter, it is evident that L-Fd4C is
      endowed with exceptional anti-HBV activity (both in vitro and in vivo) as well as
      an acceptable toxicity profile, thus rendering it a very promising development
      candidate.

PMID- 11966453
TI  - Non-peptide antagonists and agonists of the bradykinin B(2) receptor.
AB  - Stimulation of the bradykinin (BK) B(2) receptor by kinins is associated with
      pathophysiological as well as pronounced beneficial effects. Consequently,
      interference with BK B(2) receptors by either antagonism or agonism offers
      promising therapeutic approaches for the development of drugs for the treatment
      of various human diseases. BK B(2) receptor antagonists may prove useful for the
      treatment of pathological situations caused by excessively increased local kinin
      concentrations, such as inflammation, tissue injury and pain. Beneficial effects
      of peptide BK B(2) receptor antagonists in perennial rhinitis, asthma and brain
      edema have already been demonstrated in clinical trials. On the other hand,
      kinins have also been identified as potent vasodilatory and organ-protective
      peptides. Therefore, BK B(2) receptor agonists may have the potential to become
      valuable therapeutics in the treatment of cardiovascular diseases such as
      hypertension, myocardial hypertrophy, myocardial infarction and arrhythmias as
      well as diabetic disorders. For both approaches, potent, selective and even
      orally active non-peptide compounds have been discovered recently. Prototypes of
      these novel third generation classes of compounds are the alkylphosphonium salt
      WIN-64338, the pseudopeptide NPC-18884, the thiosemicarbazide bradyzide and
      especially the imidazo[1,2-a]pyridine FR-167344 and the quinolines FR-173657 and
      LF-16.0687 as non-peptide BK B(2) receptor antagonists, whereas the 4-(2
      pyridylmethoxy)-substituted quinoline FR-190997 and the 3-(2-pyridylmethyl)
      substituted benzimidazole FR-191413 emerged as non-peptide BK B(2) receptor
      agonists. These antagonists and agonists of the BK B(2) receptor have already
      demonstrated efficacy a various animal models of human diseases, which offers
      promising therapeutic approaches for the development of drugs for the treatment
      or even prevention of a variety of severe human diseases either via stimulation
      or via blockade of BK B(2) receptors.

PMID- 11966454
TI  - Aminoglycoside mimetics as small-molecule drugs targeting RNA.
AB  - The potential of RNA as a new drug target has recently come to the fore, with the
      recognition that RNA molecules can adopt complex three-dimensional structures
      that, as with proteins, enable the design of specific ligands. Another reason for
      the present interest comes from the fact that many pathogenic agents, such as
      retroviruses, encode their genetic information in RNA strands. Unfortunately, the
      high toxicity and rapid emergence of high-level resistance have severely limited
      the usefulness of naturally occurring aminoglycoside antibiotics. To tackle these
      problems, it is an important concern to design new synthetic compounds with
      smaller, simpler structures which possess higher RNA binding affinity, better
      selectivity, better antibiotic activity, and stronger resistance against the
      aminoglycoside-modifying enzymes compared to their parent structures. Here, we
      will attempt a survey of current efforts to develop aminoglycoside mimetics or
      derivatives that target RNA. The latest advances in this field including rational
      design, synthetic strategy, and structure activity relationships are reviewed.

PMID- 11966455
TI  - New trends in dual 5-LOX/COX inhibition.
AB  - Dual inhibitors are drugs able to block both the COX and the 5-LOX metabolic
      pathways. The interest of developing such compounds is supported by a large
      number of pharmacological studies. Compared to COX or LOX pathways single
      inhibitors, dual inhibitors present at least two major advantages. First, dual
      inhibitors, by acting on the two major arachidonic acid metabolic pathways,
      possess a wide range of anti-inflammatory activity. Secondly, dual inhibitors
      appear to be almost exempt from gastric toxicity, which is the most troublesome
      side effect of COX inhibitors. The mechanism of their gastric-sparing properties
      is not completely understood, although it has been demonstrated that leukotrienes
      significantly contribute to the gastric epithelial injury. Finally, both COX and
      LOX derivatives (prostanoids and leukotrienes, respectively) are involved in
      other diseases than inflammation such as cancer proliferation where the use of
      dual inhibitors could be an interesting approach.

PMID- 11966456
TI  - Converting a peptide into a drug: strategies to improve stability and
      bioavailability.
AB  - The discovery of peptide hormones, growth factors and neuropeptides implicated in
      vital biological functions of our organism has increased interest in therapeutic
      use of short peptides. However, the development of peptides as clinically useful
      drugs is greatly limited by their poor metabolic stability and low
      bioavailability, which is due in part to their inability to readily cross
      membrane barriers such as the intestinal and blood-brain barriers. The aim of
      peptide medicinal chemistry is, therefore, to develop strategies to overcome
      these problems. Recent progress in chemical synthesis and design have resulted in
      several strategies for producing modified peptides and mimetics with lower
      susceptibility to proteolysis and improved bioavailability, which has increased
      the probability of obtaining useful drugs structurally related to parent
      peptides. This review describes different experimental approaches to transforming
      a peptide into a potential drug and provides examples of the usefulness of these
      strategies.

PMID- 11966457
TI  - Thiol-dependent enzymes and their inhibitors: a review.
AB  - Biological thiol-dependent enzymes have recently received extensive attention in
      the literature because of their involvement in a variety of physiopathological
      conditions. The active thiol groups of these enzymes are derived from the
      cysteine residues present. Hence, in a biological system, the selective
      reversible or irreversible inhibition of the activity of these enzymes by
      modification of the thiol moiety may potentially lead to the development of a
      chemotherapeutic treatment. Despite all the research efforts involved in the
      attempt to develop potential chemotherapeutic treatments for the major diseases
      involving cysteine proteases, there are in fact no such treatments available yet.
      However, AG7088 (1) an inhibitor of rhinovirus-3C is in phase II/III clinical
      trial for the treatment of common cold and VX-740 (2, pralnacasan) an inhibitor
      of caspase-1 is in phase II clinical trial as an anti-inflammatory agent for
      rheumatoid arthritis. Several other cysteine protease inhibitors (i.e., cathepsin
      K, and S) are in pre-clinical evaluation or pre-clinical development. Structure
      based drug design approaches have been instrumental in the development of these
      inhibitors. Intensive biochemical studies on the cysteine proteases have shed
      some light on some potential targets for therapeutic development. In addition,
      new techniques and new ideas are constantly emerging. As such, an up-to-date
      review of the literature on thiol-dependent enzymes as potential targets and
      their inhibitors designed from peptidic, modified peptidomimetic scaffolds and
      from small heterocyclic molecules is presented.

PMID- 11966458
TI  - Alzheimer's disease: an overview of current and emerging therapeutic strategies.
AB  - Alzheimer's Disease (AD) is a progressive neurodegenerative disease that is
      prevalent among the elderly. It is a heterogeneous disease involving a number of
      genetic components, risk factors and other poorly defined elements that all
      impact on the accumulation of beta-amyloid peptide (Abeta). Current understanding
      of pathology, biochemistry and genetics strengthens the notion that Abeta is
      potentially the common pathogenic agent in an apparent convergence of various
      mechanisms leading to the decline of cognitive function and neuronal loss. While
      many issues remain controversial, recent evidence attributing Abeta accumulation
      to cognitive decline in humans, coupled to the demonstrated improvement of
      cognitive function following Abeta immunization in pre-clinical models, strongly
      supports the "amyloid hypothesis" and a central role for Abeta; in the
      pathophysiology and etiology of AD. These and other observations endorse the
      notion that therapeutic strategies targeting the inhibition of Abeta accumulation
      by the use of protease inhibitors,immunization or other strategies, may provide
      disease-altering interventions to the development and progression of AD. The only
      approved and marketed treatments currently available for AD are the
      acetylcholinesterase inhibitors, a palliative strategy aimed at the temporary
      improvement of cognitive function. The purpose of this overview is to provide a
      brief understanding of key events leading to the progression of AD and to
      highlight a few of the current and most promising therapeutic strategies that one
      day might be available for the treatment of AD.

PMID- 11966459
TI  - Cholinergic agonists and the treatment of Alzheimer's disease.
AB  - Over the past decade, considerable effort was focused on the development of
      muscarinic and nicotinic agonists for the treatment of Alzheimer's disease. The
      rationale for developing muscarinic agonists was based on the role of
      acetylcholine in learning and memory function and the consistent neurochemical
      finding that cholinergic neurons degenerated in Alzheimer's patients. Thus far,
      the clinical utility of muscarinic agonists remains unproven, yet recent studies
      suggest that muscarinic agonists might be useful in treating not only memory
      deficits, but also psychiatric disturbances and some of the underlying causes of
      Alzheimer's disease, such as the deposition of Abeta. In addition, nicotinic
      receptors may play a role in cognitive function and help regulate the toxicity of
      amyloid precursor protein. Ultimately, cholinergic agonists may prove useful in
      the treatment of Alzheimer's disease.

PMID- 11966460
TI  - Inhibition of BACE, a promising approach to Alzheimer's disease therapy.
AB  - The first proteolytic step in the processing of amyloid precursor protein (APP)
      to amyloid-beta (Abeta) in the brain is performed by beta-site APP cleaving
      enzyme (BACE1). This enzyme is a membrane bound aspartic protease with high
      homology of the catalytic domain to renin and pepsin and of yet unknown
      physiologic function. It is a primary drug discovery target for Alzheimer s
      disease therapy. The first potent inhibitors are based on the sequence of APP
      around the beta-secretase cleavage site EVNL/DAEF, with the scissile Leu-Asp
      amide bond being replaced by a hydroxyethylene transition state analogue
      isostere. In addition, lipophilic sidechains have been incorporated and a crystal
      structure of such an octapeptidic inhibitor bound in the active site is already
      available. Recent progress in the field of BACE inhibition is reviewed.

PMID- 11966461
TI  - Secretase as a target for Alzheimer's disease.
AB  - The amyloid-beta peptide (Abeta) is the major protein component of the
      characteristic cerebral plaques of Alzheimer s disease (AD), and a large body of
      evidence supports a pathogenic role for this peptide. Thus, the proteases beta-
      and gamma-secretase that are responsible for carving Abeta out of its precursor
      protein are considered prime targets for therapeutic design. beta-Secretase is a
      membrane-anchored aspartyl protease of the pepsin family, while gamma-secretase
      is much more complex. gamma-Secretase requires presenilin, a multipass membrane
      protein that is the site of dozens of missense mutations that alter Abeta
      formation and cause hereditary AD. Two conserved aspartates in presenilin are
      required for gamma-secretase activity, and aspartyl protease transition-state
      analogue inhibitors of gamma-secretase bind directly to presenilins, strong
      evidence that presenilin is the catalytic component of a novel membrane aspartyl
      protease. gamma-Secretase appears to be a multi-component complex of integral
      membrane proteins, and so far presenilin and a single-pass membrane protein
      called nicastrin have been identified as members of this complex. A closely
      similar or identical protease activity is essential for a signaling pathway
      critical for embryogenesis and hematopoiesis, raising concerns about gamma
      secretase as a target. The development of potent and selective inhibitors with
      good pharmacokinetic properties may soon address these concerns.

PMID- 11966462
TI  - Structural and functional neuroimaging in Alzheimer's disease: an update.
AB  - The field of neuroimaging has made several recent advances understanding
      Alzheimer's disease, a debilitating disease which affects approximately 4 million
      people in the United States [1]. Despite recent therapeutic advances, available
      treatments at present are aimed primarily at slowing progression of the disease
      rather than halting it completely or reversing its progression. Early detection
      of the disease has, therefore, been a major focus of a variety of neuroimaging
      techniques, including Positron Emission Tomography (PET), functional Magnetic
      Resonance Imaging (fMRI), and structural MRI. Recently, these techniques have
      also been found to be useful in monitoring cognitive and pathological progression
      of the disease, as well as monitoring response to clinical intervention
      treatment. A methodology review will be included here as well as a critical
      evaluation of the advantages and disadvantages of the various techniques.

PMID- 11966463
TI  - Tau protein phosphorylation as a therapeutic target in Alzheimer's disease.
AB  - Neurofibrillary tangles (NFTs) are a distinguishing neuropathological feature
      found in postmortem brains of Alzheimer s disease (AD) and tauopathy patients.
      The density of these lesions correlates with severity of AD and their
      distribution follows a characteristic pattern of expansion as the disease
      progresses. The principle components of NFTs are highly phosphorylated forms of
      the microtubule-associated protein, tau. Tau phosphorylation is believed to
      initiate or facilitate dissociation from microtubules leading to microtubule
      destabilization, decay of cellular transport properties, and cell death. This
      review summarizes recent data and prevailing views on the roles of protein
      kinases and phosphatases in the regulation of tau phosphorylation in vitro and in
      vivo, taking into account data from human neurodegenerative diseases and from
      transgenic rodent models. Small molecule inhibitors of tau phosphorylation that
      serve as important research tools and possibly the basis of potential new
      therapeutics, are also described. Key challenges in developing effective
      therapeutic agents include identification of the relevant kinase(s) responsible
      for aberrant tau phosphorylation in AD, synthesis of inhibitors selectively
      targeting those kinases and establishment of appropriate animal models.

PMID- 11966464
TI  - Peptide inhibitors of beta amyloid aggregation.
AB  - Amyloid beta peptide (Abeta) is implicated in the pathogenesis of Alzheimer s
      disease (AD), particularly as oligomers or polymers that are correlated with
      Abeta cellular toxicity. Inhibition of the formation of toxic forms of Abeta has
      therefore emerged as one approach to the treatment of AD. This article reviews
      efforts to adapt the structure of Abeta to the design and testing of peptide
      based inhibitors of Abeta polymerization of interest as potential AD
      therapeutics.

PMID- 11966465
TI  - Target validation for drug discovery in parasitic organisms.
AB  - Parasite infections affect billions of humans world-wide, yet the current drugs
      available for the treatment of many parasitic diseases are either inadequate, or
      compromised by the development of resistance. Validation of a drug target is an
      important step in the development of new drugs. Target validation encompasses
      verifying that a target is primarily responsible for the therapeutic activity of
      a proven drug, or demonstrating the essential nature of a putative drug target in
      a parasite, and the capacity for selective inhibition of that target in vivo.
      Selective toxicity may be achieved by taking advantage of unique parasite biology
      or biochemistry, or by utilizing differences in metabolism or import. The
      essential nature of a target may be demonstrated by the correlation of the
      chemical or genetic reduction of target activity with the loss of parasite growth
      or virulence. Rescue experiments may demonstrate the single nature of a target.
      Ultimately, a target must be validated in vivo.

PMID- 11966467
TI  - The interfaces of oligomeric proteins as targets for drug design against enzymes
      from parasites.
AB  - Millions of people worldwide are infected by some kind of parasite and millions
      are in risk of contracting infection. In addition, it is now accepted that
      parasites are rapidly developing resistance to drugs that a few years ago were
      effective. This gloom picture underscores the urgent need to develop new drugs
      against parasitic diseases. Fortunately, the important technological advances
      that have been made in the past years will, in principle, facilitate the
      discovery of new and effective agents against parasitic diseases. In many of the
      approaches for drug design the basic premise is the identification of a
      macromolecule that is central to the life of the parasite. Because the life of
      all living organisms depends on multiple protein-protein interactions and the
      function of oligomeric proteins, it is worthwhile to explore if protein
      interfaces could be exploited for drug design. Here we review some of the work
      that has been done in this direction, and attempt to call attention to the
      richness of protein-protein interfaces for the design of agents that could lead
      to the development of drugs against parasitic diseases.

PMID- 11966466
TI  - Glycolysis and proteases as targets for the design of new anti-trypanosome drugs.
AB  - Glycolysis is considered as a promising target for new drugs against parasitic
      trypanosomatid protozoa, because this pathway plays an essential role in their
      ATP supply. Trypanosomatid glycolysis is unique in that it is compartmentalised,
      and many of its enzymes display specific structural and kinetic features.
      Structure- and catalytic mechanism-based approaches are applied to design
      compounds that inhibit the glycolytic enzymes of the parasites without affecting
      the corresponding proteins of the human host. For some trypanosomatid enzymes,
      potent and selective inhibitors have already been developed that affect only the
      growth of cultured trypanosomatids, and not mammalian cells. Examples are
      developed concerning all enzymes in the hexoses part with also others concerning
      glyceraldehyde-phosphate dehydrogenase and pyruvate-kinase for the trioses part.
      Concerning cysteine protease inhibitor development, a great number of
      irreversible alkylating agents have shown their efficacy towards the active site
      cysteine of parasite proteases. This includes fluoromethylketones, epoxides,
      diazomethylketones, vinylsulfones to mention a few. These functional groups are
      activated electrophiles that react with the nucleophilic cysteine of the active
      site and are generally quite selective for cysteine versus serine. They are
      thought to be also reactive to numerous other nucleophiles in the body,
      especially other thiols. This potentially hampering property seems not to be
      detrimental for two reasons: first a recent report has shown that cysteine
      protease inhibitors containing a vinylsulfone electrophile are unreactive towards
      thiols such as glutathione and can be considered to be inert in the absence of
      catalytic machinery. Secondly, irreversible inhibitors are shown to be less toxic
      than presumed in the parasite treatment, owing to some bioselectivity displayed
      by the parasite itself.

PMID- 11966468
TI  - Perspectives for new drugs against trypanosomiasis and leishmaniasis.
AB  - Diseases caused by pathogenic trypanosomatids cause great suffering throughout
      the developing world. New drugs for these diseases are urgently needed. Recent
      technological advances have permitted the identification and validation of
      numerous drug targets in these organisms. However, efforts to develop inhibitors
      of these targets, that may then be taken forward for development into new drugs,
      have been comparatively scarce. In this review we discuss the design, synthesis
      and evaluation of inhibitors of two drug targets in trypanosomatids, 6
      phosphogluconate dehydrogenase, the third enzyme of the pentose phosphate
      pathway, and dihydrofolate reductase, a key enzyme involved in DNA synthesis.
      Enzyme inhibitors can only be useful as drugs if they can enter cells and bind to
      their targets. Therefore we also discuss approaches to designing molecules that
      can specifically cross the plasma membrane of African trypanosomes via unusual
      nutrient transporters.

PMID- 11966469
TI  - Perspectives in drug design against malaria.
AB  - Development of drug resistance by Plasmodium falciparum and insecticide
      resistance by the mosquito has lead to the resurgence of the most virulent forms
      of malaria. This review aims to provide a general perspective on drug design for
      P. falciparum malaria. Though numerous targets have been identified, new
      clinically useful target-specific inhibitors remain a distant prospect. This
      review focuses on pathways and enzymes for which some structural information and
      detailed biochemistry along with specificity of inhibitor action is available.
      Aspects of the parasite glycolytic pathway, nucleotide metabolism, proteases,
      redox metabolism and organelle function have been used to highlight possible
      targets and molecules that could inhibit their function.

PMID- 11966470
TI  - Role of the interfacial binding domain in the oxidative susceptibility of
      lecithin:cholesterol acyltransferase.
AB  - We had previously shown that the cholesterol esterification activity of
      lecithin:cholesterol acyltransferase (LCAT) is destroyed by oxidation, but still
      it retains the ability to hydrolyse water-soluble substrates. This suggested that
      the inactivation of the enzyme is not due to its catalytic function, but due to a
      loss of its hydrophobic binding. Since recent studies have shown that a
      tryptophan residue in the putative interfacial domain (Trp(61)) is critical for
      the activity, we determined the possible role of this residue in the oxidative
      susceptibility and substrate specificity of LCAT by site-directed mutagenesis.
      Deletion of Trp(61) resulted in a 56% loss of cholesterol esterification (LCAT)
      activity, but the phospholipase A(2) (PLA(2)) and the esterase activities of the
      enzyme were stimulated slightly. Replacing Trp(61) with another aromatic residue
      [Trp(61)-->Tyr (W61Y)] resulted in an increase in all activities (14-157%),
      whereas replacing it with an aliphatic residue [Trp(61)-->Gly (W61G)] caused a
      dramatic loss of LCAT (-90%) and PLA(2) (-82%) activities, but not the esterase
      activity (-5%). W61Y was the most sensitive to oxidation, whereas W61G was the
      most resistant, with respect to the LCAT and PLA(2) activities. However, the
      activities which do not involve interfacial binding, namely the esterase activity
      and the transesterification of short-chain phospholipids, were more resistant to
      oxidation in all LCATs, indicating a selective loss of the interfacial binding by
      oxidation. Furthermore, replacing the two cysteines (Cys(31) and Cys(184)) in the
      Trp(61) deletion mutant caused additional resistance of the enzyme to oxidizing
      agents, showing that both domains of the enzyme contribute independently to its
      oxidative susceptibility. Since the hydrolysis of truncated phospholipids,
      generated during the oxidation of low-density lipoproteins, does not require the
      interfacial-binding domain, our results suggest that LCAT may take part in the
      detoxification of these compounds even after the loss of its cholesterol
      esterification function.

PMID- 11966471
TI  - Two essential regions for tRNA recognition in Bacillus subtilis tryptophanyl-tRNA
      synthetase.
AB  - Bacillus subtilis tryptophanyl-tRNA synthetase (TrpRS) is a homodimeric enzyme. A
      model for its ability to recognize tRNA(Trp) in B. subtilis was proposed by using
      computer modelling. This was based on the the fact that there is high homology
      among bacterial TrpRSs [Chen, Jiang, Jin and Wang (2001) Acta Biochim. Biophys.
      Sinica 33, 687-690], in which the enzyme dimer binds to two tRNA(Trp) molecules
      and each tRNA(Trp) is bound to two different domains across the surface of the
      dimer. In this work, three deletion mutants of TrpRS were constructed and their
      products were purified. After determining the kinetic parameters of the mutants
      in the two-step reaction, it was found that the relative activities of wild-type
      and mutant enzymes had changed little in the ATP-pyrophosphate exchange reaction.
      In contrast, the activities of three mutant proteins were much decreased in the
      tRNA(Trp) aminoacylation assay. Deletion of residues 108-122 and residues 234-238
      caused 44% and 80% reductions in the activity, respectively. When both regions
      were deleted, the aminoacylation activity of the TrpRS mutant was too low to be
      determined using tRNA(Trp) at the limiting concentration. Gel-retardation assays
      showed that the acceptor minihelix and the anticodon microhelix were recognized
      by the domains of TrpRS spanning residues 108-122 and residues 234-238
      respectively. In addition, the deletion of amino acids 234-238 affected the
      normal induced expression of TrpRS at 37 degrees C. In conclusion, residues 108
      122 and 234-238 were found essential for tRNA(Trp) recognition.

PMID- 11966473
TI  - Suspected big baby: a difficult clinical problem in obstetrics.
AB  - BACKGROUND: Large for gestational age fetuses, also called macrosomic fetuses,
      represent a continuing challenge in obstetrics. METHODS: We review various
      problems with large for gestational age fetuses. We have performed a literature
      search, mainly through the database PubMed (includes the Medline database). The
      clinical problem is discussed from the primary care provider's, the patient's and
      the obstetrician's point of view. RESULTS: Macrosomia is arbitrarily defined as
      having a fetal weight of above the 90th percentile, a birth weight of above 4000
      g or 4500 g, or a birth weight of over +2 standard deviation of the mean birth
      weight by gestational age. The diagnosis of macrosomia is difficult, both by
      palpation and symphysis fundus measurement; even with sophisticated sonographic
      measures. The combination of biparietal diameter, femur length and abdominal
      circumference appears to be no better than abdominal circumference alone.
      INTERPRETATION: Based on the literature, labor should not be induced in
      nondiabetic pregnancies. The best policy is to await spontaneous birth or to
      induce labor after 42 weeks completion. A great number of cesarean sections have
      to be performed to avoid a single case of plexus brachialis paresis resulting
      from a difficult shoulder delivery. Cesarean section should not be considered in
      nondiabetic pregnancies unless the estimated fetal weight is above 5000 g. In
      pregnancies complicated by diabetes mellitus there are reasons for selective
      induction of labor if macrosomia is suspected and for cesarean section if the
      calculated birth weight is above 4000 g. Each department should have a strategy
      to handle such a situation because the problem with the difficult shoulder
      delivery cannot be completely avoided. Different procedures of managing difficult
      shoulder delivery are described.

PMID- 11966472
TI  - Embryonic extracts derived from the nematode Caenorhabditis elegans remove uracil
      from DNA by the sequential action of uracil-DNA glycosylase and AP
      (apurinic/apyrimidinic) endonuclease.
AB  - DNA bases continuously undergo modifications in response to endogenous reactions
      such as oxidation, alkylation or deamination. The modified bases are primarily
      removed by DNA glycosylases, which cleave the N-glycosylic bond linking the base
      to the sugar, to generate an apurinic/apyrimidinic (AP) site, and this latter
      lesion is highly mutagenic. Previously, no study has demonstrated the processing
      of these lesions in the nematode Caenorhabditis elegans. Herein, we report the
      existence of uracil-DNA glycosylase and AP endonuclease activities in extracts
      derived from embryos of C. elegans. These enzyme activities were monitored using
      a defined 5'-end (32)P-labelled 42-bp synthetic oligonucleotide substrate bearing
      a single uracil residue opposite guanine at position 21. The embryonic extract
      rapidly cleaved the substrate in a time-dependent manner to produce a 20-mer
      product. The extract did not excise adenine or thymine opposite guanine, although
      uracil opposite either adenine or thymine was processed. Addition of the highly
      specific inhibitor of uracil-DNA glycosylase produced by Bacillus subtilis to the
      extract prevented the formation of the 20-mer product, indicating that removal of
      uracil is catalysed by uracil-DNA glycosylase. The data suggest that the 20-mer
      product was generated by a sequential reaction, i.e., removal of the uracil base
      followed by 5'-cleavage of the AP site. Further analysis revealed that product
      formation was dependent upon the presence of Mg(2+), suggesting that cleavage of
      the AP site, following uracil excision, is carried out by a Mg(2+)-dependent AP
      endonuclease. It would appear that these activities correspond to the first two
      steps of a putative base-excision-repair pathway in C. elegans.

PMID- 11966474
TI  - Expression of cadherins and CD44 isoforms in human endometrium and peritoneal
      endometriosis.
AB  - BACKGROUND: To evaluate (a) cadherins and CD44 expression in normal endometrium
      and in peritoneal endometriosis, and (b) to correlate, their expressions with
      clinicopathological parameters. METHODS: E- and N-cadherin, CD44 isoforms, CD44v3
      and CD44v6 expressions were evaluated: (a) by immunoblotting in endometrium (n =
      6) and in peritoneal endometriotic samples (n = 7) and, (b) by
      immunohistochemistry in endometrium (n = 15) and in peritoneal endometriotic
      samples (n = 23). RESULTS: By immunoblotting, endometrium expressed E- and N
      cadherin, CD44 isoforms, CD44v3 and CD44v6. Similar results were observed in
      peritoneal endometriosis. By immunohistochemistry, in endometrium, E-cadherin was
      restricted to epithelial cells. Its expression remained constant throughout the
      menstrual cycle. N-cadherin was detected in both epithelial and stromal cells in
      the proliferative phase but was restricted to epithelial cells in the secretory
      phase. CD44 immunostaining was detected in the secretory but not in the
      proliferative phase. Decreased expression of E-cadherin (p < 0.01) and CD44 (p <
      0.01) in epithelial cells was found in peritoneal endometriosis as compared with
      normal endometrium. In endometriotic stromal cells, decreased CD44 expression was
      found. In peritoneal endometriosis, we observed a decreased expression of E
      cadherin in advanced stages of the disease (p < 0.01). CONCLUSION: Our results
      suggest that E-cadherin and CD44 proteins could be involved in the development of
      endometriotic lesions. Investigation of the mechanisms of altered adhesion
      molecule expression may contribute to the understanding of the behavior of
      endometriotic cells.

PMID- 11966475
TI  - Management and outcome of pregnancy in women with thrombophylic disorders and
      past cerebrovascular events.
AB  - OBJECTIVE: To evaluate the maternal and fetal outcome in a cohort of women
      undergoing a subsequent pregnancy after a previous cerebrovascular event in the
      presence of thrombophilia. PATIENTS: Fifteen pregnancies were followed up in 12
      women with past cerebrovascular events and thrombophilic disorders. The
      cerebrovascular events occurred during a previous pregnancy in five patients. Six
      patients had a bad obstetric history including intrauterine fetal death in four
      cases, early onset of severe preeclampsia in two cases and one infant that was
      small for gestational age. THE THROMBOPHILIC DISORDERS INCLUDED: anti
      phospholipid syndrome, protein C, S or antithrombin III deficiencies, mutations
      of the methyltetrahydrofolate reductase (MTHFR). All patients received
      prophylactic treatment with low molecular weight heparin and low dose aspirin.
      RESULTS: Thromboembolic complications occurred in four pregnancies. Postpartum
      complications occurred in one patient; deep vein thrombosis and pulmonary emboli
      after stopping anticoagulation treatment. No patient had long-term neurologic
      damage. All pregnancies except one resulted in live births. (mean gestational age
      at delivery 36 +/- 3. 7 weeks, mean birth weight 2656 +/- 811 g). The one
      remaining pregnancy was electively terminated. There was one neonatal death due
      to the complications of severe prematurity in a woman with severe HELLP syndrome.
      CONCLUSION: This preliminary data suggests that women with a history of
      cerebrovascular events and thrombophilic disorders receiving prophylactic
      treatment, have a relatively favorable pregnancy outcome; however, they remain at
      significant risk during pregnancy. Further studies are necessary to determine the
      optimal prophylactic treatment.

PMID- 11966476
TI  - The levels of five markers of hemostasis and endothelial status at different
      stages of normotensive pregnancy.
AB  - BACKGROUND: Urinary 11-dehydrothromboxane B(2)/creatinine (11-DTXB(2)/Cr) is a
      marker for in vivo platelet activation and vascular constriction, blood
      thrombomodulin (TM) for endothelial damage and associated thrombosis, thrombin
      antithrombin complex (TAT) for thrombin formation, and beta-thromboglobulin (beta
      TG) and platelet factor 4 (PF-4) for in vivo platelet activation and releasing
      reaction. Little is known about the quantitative relationship among them during
      pregnancy. The present study investigated levels of five markers at different
      stages of normotensive pregnancy. METHODS: Subjects were 17 healthy non-pregnant
      women (Group 1, control) and 67 women carrying single fetuses in normotensive
      pregnancy. Of the pregnant women, 17 were in the 20th week of gestation (Group
      2), 20 were in their 30th week (Group 3), and 30 were in their 36th week (Group
      4). Urinary and circulating blood levels of 11-DTXB(2)/Cr, TM, TAT, beta-TG, and
      PF-4 were measured simultaneously. RESULTS: The 11-DTXB(2)/Cr and TAT levels
      showed elevated values at the 20th and 30th weeks of gestation, and markedly
      elevated values at the 36th week, whereas the TM level remained constant
      throughout pregnancy. The beta-TG and PF-4 levels maintained stable values at the
      20th week, but showed elevated values at the 30th and 36th weeks. CONCLUSIONS:
      Platelet aggregation, vascular constriction, and thrombin formation (detected by
      11-DTXB(2)/Cr and TAT) appear to be enhanced as early as the 20th week of
      gestation, continuously enhanced by the 30th week, and markedly enhanced by the
      36th week. Platelet activation and releasing reaction (determined by beta-TG and
      PF-4) gradually enhanced from the 30th to 36th weeks. In contrast, endothelial
      damage and associated thrombosis (detected by TM) were minimal throughout
      pregnancy. Investigating these markers of hemostasis and endothelial function in
      normotensive pregnancy may provide insights into related disease states.

PMID- 11966477
TI  - The prognostic impact of a prolonged second stage of labor on maternal and fetal
      outcome.
AB  - OBJECTIVE: While obstetrical management has changed significantly over years, the
      optimal duration of the second stage of labor still remains to be defined. The
      purpose of this study was to evaluate the effect of the duration of labor on
      fetal distress and maternal perinatal morbidity. METHODS: There were 1457
      consecutive patients delivered of a singleton fetus in cephalic presentation
      beyond the 34th week of gestation at the I. Frauenklinik, Ludwig-Maximilians
      University, Munich between May 1999 and June 2000. The 257 patients (17.6%), who
      underwent cesarean section prior to or during labor, were excluded from the
      study. Of the 1200 vaginal deliveries, 1017 (84.8%) were normal spontaneous
      deliveries, while 183 (15.2%) were instrumentally assisted. Data were
      contemporaneously collected and analyzed for the presence of severe pelvic floor
      damage, maternal hemorrhage, maternal fever, delayed involution of the uterus,
      fetal acidosis and APGAR score, and the necessity for admitting the newborn to
      the intensive care unit (NICU). A second stage duration of > 2 hr was considered
      to be prolonged. RESULTS: The mean duration of the second stage of labor was 70
      min (range 2-387, SD 73 min). For 952 patients (79.3%), the second stage was less
      than 2 h. For 47 patients (3.9%), it exceeded 4 h. A prolonged duration of the
      second stage was not associated with low Apgar scores 5 and 10 min postpartum (P
      = 0.76 and P = 0.38, respectively), a higher incidence of umbilical artery pH
      levels of < 7.20 (P = 0.60), nor with an increased rate of admission to the NICU
      (P = 0.24). A significant increase in the rate of maternal blood loss was noted
      after long second stages (1.84 g/dl median difference between the intrapartum and
      postpartum hemoglobin level) in comparison to patients with normal duration of
      second stage (0.79 g/dl), both by univariate (P < 0.0001) and multivariate (P <
      0.001) analysis. The incidence of third degree anal sphincter tears was
      significantly correlated with a prolonged duration of second stage in univariate
      analysis (7.7%, P = 0.001), but not in multivariate analysis after allowing for
      duration of the second stage, maternal age, birth weight, episiotomy, and mode of
      delivery (P = 0.26). CONCLUSION: There is no evidence that prolonged second stage
      of labor is a serious disadvantage to the fetus, if adequate monitoring is
      provided. Because the increase of maternal morbidity in patients with prolonged
      labor may be partially attributed to a higher rate of operative procedures in
      these patients, interventions should not be solely based on the elapsed time
      after full cervical dilatation.

PMID- 11966478
TI  - Risk factors and outcome of failure to progress during the first stage of labor:
      a population-based study.
AB  - BACKGROUND: One of the major indications for Cesarean section (CS) is failure of
      labor to progress. This study was aimed at defining obstetric risk factors for
      failure of labor to progress during the first stage, and to determine pregnancy
      outcome. METHODS: A population-based study comparing all singleton, vertex, term
      deliveries between the years 1988 and 1999 with an unscarred uterus, complicated
      with failure of labor to progress during the first stage with deliveries without
      non-progressive labor (NPL). Multiple logistic regression analysis was performed
      to investigate independent obstetric risk factors associated with failure of
      labor to progress during the first stage. RESULTS: Failure to progress during the
      first stage of labor complicated 1.3% (n = 1197) of all deliveries included in
      the study (n = 92 918), and resulted in CS. Independent risk factors for failure
      of labor to progress during the first stage, using a multivariable analysis, were
      premature rupture of membranes (PROM; OR = 3.8, 95% CI 3.2-4.5), nulliparity (OR
      = 3.8, 95% CI 3.3-4.3), labor induction (OR = 3.3, 95% CI 2.9-3.7), maternal age
      > 35 years (OR = 3.0, 95% CI 2.6-3.6), birth weight > 4 kg (OR = 2.2, 95% CI 1.8
      2.7), hypertensive disorders (OR = 2.1, 95% CI 1.8-2.6), hydramnios (OR = 1.9,
      95% CI 1.5-2.3), fertility treatment (OR = 1.8, 95% CI 1.4-2.4), epidural
      analgesia (OR = 1.6, 95% CI 1.4-1.8) and gestational diabetes (OR = 1.4, 95% CI
      1.1-1.7). Although newborns delivered after failure of labor to progress during
      the first stage had significantly higher rates of Apgar scores lower than 7 at 1
      and 5 min as compared with the controls (18.2% vs. 2.1%; P < 0.001 and 1.3% vs.
      0.2%; P < 0.001, respectively), no significant differences were noted between the
      groups regarding perinatal mortality (0.3% vs. 0.4%; P = O.329). Maternal anemia
      and accordingly packed cells transfusion (47.4% vs. 22.8%; P < 0.001 and 5.6% vs.
      1.0%; P < 0.001, respectively) were higher among pregnancies complicated with
      failure of labor to progress during the first stage as compared with the
      controls. CONCLUSIONS: Major risk factors for failure of labor to progress during
      the first stage were PROM, nulliparity, induction of labor and older maternal
      age. Indications for labor induction should be carefully evaluated in order to
      decrease the rate of operative deliveries.

PMID- 11966479
TI  - Ultrasonographic monitoring of pregnancies complicated by red blood cell
      alloimmunization in a cohort with mild to moderate risk according to previous
      obstetric outcome.
AB  - AIM: To evaluate the detection rate of fetal anemia and pregnancy outcome as
      related to our policy of monitoring pregnancies with red blood cell
      alloimmunization. METHODS: From August 1997 to July 2000 35 pregnant women with
      maternal red blood cell alloantibodies were monitored by ultrasonographic
      measurements of the fetal spleen perimeter and peak systolic Doppler flow
      velocities of the middle cerebral artery, by semiquantification of maternal
      antibody titers and by general ultrasonographic and clinical evaluation.
      According to previous obstetric outcome they all had mild to moderate risk of
      developing fetal anemia. RESULTS: Eleven fetuses were anemic defined as a
      hemoglobin value < or = 2SD according to gestational age. A spleen perimeter > +
      2SD and a middle cerebral artery peak systolic velocity > 95% prediction interval
      showed sensitivity and specificity of 64 and 92% and 45 and 100%, respectively.
      The area under receiver operating characteristic curves was 0.926 (95% CI 0.842
      1.000; P < 0.001) for the spleen perimeter and 0.837 (95% CI 0.688-0.987; P <
      0.01) for the middle cerebral artery peak systolic velocity. Cordocentesis was
      performed in one pregnancy only. None of the fetuses developed hydrops and all
      infants survived. Twelve women delivered before 37 weeks gestation. In 10
      patients cesarean section was performed due to possible fetal anemia. Six of the
      10 neonates had normal hemoglobin values. CONCLUSIONS: The ultrasonographic
      parameters did not predict all cases of fetal anemia defined as a hemoglobin
      concentration < or = 2SD according to gestational age. The present policy of
      monitoring seemed to reduce the number of invasive tests but possibly increased
      the number of preterm and cesarean deliveries.

PMID- 11966480
TI  - Risk of intrauterine growth retardation, malformations and other birth outcomes
      in children after topical use of corticosteroid in pregnancy.
AB  - BACKGROUND: Topical corticosteroids are frequently used drugs, but little is
      known of the exposure during pregnancy and birth outcome. METHODS: In a
      population-based follow-up study restricted to primigravida women, we examined
      the risk of low birth weight, malformations and other birth outcomes following
      pregnancy upon exposure to topical corticosteroids. We compared the offspring of
      363 women exposed to topical corticosteroids during pregnancy with 9263 controls,
      who received no prescriptions at all. RESULTS: The prevalence of malformations
      was 2.9% among 170 infants exposed during the first trimester and 3.6% among the
      controls. Adjusted odds ratios for low birth weight, malformations and preterm
      delivery among women receiving weak/medium strong corticosteroids were 0.7 (95%
      CI 0.17-2.85), 0.93 (95% CI 0.23-3.80) and 1.04 (95% CI 0.56-1.92), respectively,
      and adjusted odds ratios for strong/very strong corticosteroids were 1.23 (95% CI
      0.45-3.37), 0.56 (95% CI 0.14-2.28) and 0.99 (95% CI 0.54-1.84), respectively.
      CONCLUSIONS: The study showed no increased risk of low birth weight,
      malformations or preterm delivery in the offspring of women exposed to topical
      corticosteroid during pregnancy.

PMID- 11966481
TI  - Smoking during pregnancy: comparison of self-reports and cotinine levels in 496
      women.
AB  - OBJECTIVE: To validate self-reported smoking habits in smoking pregnant women and
      estimate the prevalence of substantial exposure to passive smoking in non-smoking
      pregnant women. DESIGN: Retrospective, quantitative study, consecutively
      collected samples. SETTING: One antenatal clinic in Blekinge County, Sweden.
      SUBJECTS: 509 pregnant women. METHOD: Information about smoking habits were taken
      from the antenatal records of 496 women (97%). Serum samples from these women
      were tested for cotinine, a nicotine metabolite. MAIN OUTCOME MEASURES: Self
      reported smoking habits and cotinine levels in ng/mL. RESULTS: Of 407 women,
      reporting to be non-smokers, 6% were most likely smokers, and 3% had cotinine
      levels suggesting exposure to substantial passive smoking. Of 60 women, reporting
      smoking 1-10 cigarettes per day, 32% were likely to smoke more. CONCLUSION: If
      the true facts about exposure to tobacco smoke are not revealed, a number of
      women who might benefit from information and support at the antenatal clinic will
      miss the opportunity of such assistance, resulting in increased risks for both
      the woman and her fetus.

PMID- 11966482
TI  - Amniotic fluid erythropoietin concentrations differentiate between acute and
      chronic causes of fetal death.
AB  - BACKGROUND: Increased fetal plasma erythropoietin concentration is an indicator
      of chronic fetal hypoxia. Amniotic fluid erythropoietin levels correlate highly
      significantly with fetal erythropoietin levels before labor. We studied AF
      erythropoietin levels after fetal death in order to determine whether this could
      differentiate between stillbirths from acute or chronic causes. METHODS: Amniotic
      fluid was obtained after fetal death for erythropoietin measurement following
      fetal death in 21 pregnancies. Two of the pregnancies had twins, of which one
      infant was born alive. All 22 stillborn fetuses had an autopsy. None had
      malformations. Without prior knowledge of the results of the erythropoietin
      analyzes, the causes of fetal death were divided into acute, chronic or unknown
      groups. RESULTS: Eight pregnancies had an acute cause of fetal death (e.g. cord
      complication or placental abruption), eight pregnancies had a chronic cause
      (intrauterine growth restriction or erythroblastosis) and in five pregnancies the
      cause of fetal death could not be determined. In all eight pregnancies with an
      acute cause of fetal death, AF erythropoietin levels were normal (< 20 mU/mL). In
      contrast, six of the eight pregnancies with a chronic cause had AF erythropoietin
      levels above normal (range from 49.9 mU/mL to 391 mU/mL). In the five pregnancies
      with an unknown cause of fetal death, AF erythropoietin levels were normal in
      three and elevated in two. CONCLUSIONS: Elevated AF erythropoietin levels,
      identified after fetal death, suggest that the fetus died from a chronic hypoxic
      event, whereas normal AF erythropoietin levels suggest that the fetus died from
      an acute event.

PMID- 11966483
TI  - Induction of labor in toxemia with misoprostol.
AB  - BACKGROUND: To compare the efficacy and complications of intravaginal misoprostol
      application with oxytocin infusion for induction of labor in toxemia of pregnancy
      with a modified Bishop score of < or =4. METHODS: A hundred preeclamptic women
      with a modified Bishop score of < or =4 were randomized into two groups of 50
      patients one group receiving 50 microg intravaginal misoprostol 4 times at 4 hour
      intervals, the second group receiving oxytocin infusion for induction of labor
      starting from 1 mIU/per minute, increasing it every 30 minutes with 2 mIU/per
      minute increments up to maximum of 30 mIU/per minute. Modified Bishop scores 12
      hours after induction, the time from induction to delivery, the route of
      delivery, fetal outcome and maternal complications were recorded. Statistical
      analyses were performed using Mann Whitney-U, Chi-Square and hypothesis tests
      about differences for two proportions (t test) to determine differences between
      the two groups. p< or =0.05 was considered significant. RESULTS: Misoprostol was
      significantly superior for induction of labor in toxemia of pregnancy with
      modified Bishop score of < or =4. After 12 hours median modified Bishop scores of
      misoprostol administered group and oxytocin administered group were 7 and 4
      respectively. Misoprostol administered group 1 was significantly better than
      oxytocin administered group 2 (p=0.027). The rate of patients who were in labor
      after 12 hours were 94% and 80% in group 1 and 2 respectively and the difference
      showed significant difference (p<0.05). The median time from induction to
      delivery was 14 hours and 16 hours in the misoprostol and oxytocin administered
      group respectively with significant difference between the groups (p=0.003). The
      rate of vaginal delivery was significantly higher in the misoprostol administered
      group 1 (82%) when compared with the oxytocin administered group 2 (66%)
      (p<0.05). The 1 and 5 minutes median Apgar scores were 5-7 and 6-7.5 in group 1
      and 2, respectively with no significant differences between the groups (p=0.96,
      p=0.64). The rate of admission to neonatal intensive care unit was similar in
      both groups. The complication rates were similar in all groups and no significant
      detrimental effects were noted. CONCLUSIONS: Intravaginal misoprostol is an
      efficacious, cheap and safe method of induction of labor in toxemia of pregnancy
      with modified Bishop score of < or =4.

PMID- 11966484
TI  - Treatment of gestational diabetes with short- or long-acting insulin and neonatal
      outcome: a pilot study.

PMID- 11966485
TI  - Ovarian carcinoma associated with pregnancy. A review of 9 cases.
AB  - BACKGROUND: The purpose of this study was to review patients with ovarian cancer
      in pregnancy, the effectiveness of the available methods of treatment and their
      prognosis. METHODS: A retrospective review of all women diagnosed to have cancer
      of the ovary associated with pregnancy who delivered at the authors' hospitals
      between January 1976 and December 2000. The demography, clinical presentation,
      time and mode of diagnosis, treatment, pregnancy outcome and maternal survival
      were noted. RESULTS: The incidence of ovarian carcinoma in pregnancy in the
      series was 0.08/1000 deliveries. Of the 9 patients, 7 had epithelial cancers; 4
      serous cystadenocarcinoma, 2 mucinous cystadenocarcinomas and one
      undifferentiated cancer. One patient each had dysgerminoma and granulosa cell
      tumor. Six patients were in FIGO stage Ia, one Ic, one IIa. One patient was in
      stage III. Five patients were treated by unilateral salpingo-oophorectomy during
      pregnancy. Three patients had total abdominal hysterectomy, bilateral salpingo
      oophorectomy and omentectomy followed by chemotherapy. Debulking of the tumor was
      done in a patient in stage III with subsequent chemotherapy. This patient died 13
      months from the time of diagnosis of the tumor. The overall 5-year survival rate
      in the series was 78% and 100% for stage Ia. CONCLUSIONS: Association of ovarian
      cancer with pregnancy is a rare occurrence. Early diagnosis and appropriate
      treatment offers the best prognosis for the patient. The higher survival rates in
      the series was attributed to a larger number of patients in stage I of the
      disease and 2 patients with a germ cell tumor and dysgerminoma which have the
      best prognosis. Aggressive postoperative chemotherapy also contributed to the
      better outcome.

PMID- 11966487
TI  - Postpartum urethral prolapse.

PMID- 11966486
TI  - Pregnancy in hyperprolactinemic women.

PMID- 11966488
TI  - Preoperative vena caval interruption for venous thrombosis associated with
      ovarian malignancy.

PMID- 11966489
TI  - Prelabor rupture of the membranes in a splenectomised patient with subsequent
      maternal and fetal sepsis.

PMID- 11966490
TI  - Oocyte donation using immature oocytes from a normal ovulatory woman.

PMID- 11966492
TI  - Review article: is clinical remission the optimum therapeutic goal in the
      treatment of Crohn's disease?
AB  - Currently, the therapeutic end-point in the treatment of Crohn's disease is the
      remission of symptoms, but recent data confirm that mucosal inflammation may
      continue in the absence of symptoms. Furthermore, emerging evidence indicates
      that such subtle, sub-clinical mucosal inflammation leads to clinical relapse.
      The assessment of mucosal inflammation has become easier with the availability of
      faecal calprotectin assay. Current anti-inflammatory therapy often leaves low
      grade mucosal inflammation untreated, and therefore recurrent relapses occur. We
      need to investigate whether the therapeutic end-point of anti-inflammatory
      medications needs to be more rigorous and to aim at complete mucosal healing,
      confirmed by the normalization of mucosal inflammatory markers such as faecal
      calprotectin concentrations. Immunosuppressive therapy with azathioprine/ 6
      mercaptopurine currently offers the best mucosal healing treatment with reduction
      of relapses, but newer biological agents might offer less toxic therapy. Clinical
      trials to test the feasibility and efficacy of such a paradigm shift in the
      medical management of Crohn's disease are now warranted.

PMID- 11966493
TI  - Baclofen-mediated gastro-oesophageal acid reflux control in patients with
      established reflux disease.
AB  - AIM: To explore the effect of baclofen on oesophageal acid exposure in patients
      with gastro-oesophageal reflux disease. METHODS AND MATERIALS: Twenty patients
      with established reflux disease were included in this double-blind, randomized,
      crossover study. Baclofen, 40 mg, or placebo was given as a single dose with a
      washout period of 4 weeks. Symptoms were assessed by a visual analogue scale.
      Oesophageal pH was registered for 12 h and analysed for the whole period and for
      the 0-4-h, 4-8-h, 8-12-h and 2-h post-prandial periods. RESULTS: Baclofen
      significantly reduced the number of reflux episodes during the 0-4-h (7.9 vs.
      16.5, P < 0.0001; post-prandially: 6.0 vs. 11.2, P < 0.0001) and 0-12-h (46.5 vs.
      73, P=0.0001; post-prandially: 18.8 vs. 29.3, P < 0.0001) periods. The fraction
      of time with pH < 4 was significantly lowered during the 0-4-h period (9.3 vs.
      15.6, P=0.0019; post-prandially: 16.1 vs. 23.5, P=0.0083). Similar results were
      also obtained in patients with a hiatus hernia (n=13). Belching was significantly
      reduced (32 vs. 69 episodes, P < 0.01). CONCLUSIONS: A single oral dose of 40 mg
      baclofen significantly reduced both the number of reflux episodes and the
      fraction of time with pH < 4, an effect primarily found during the first 4 h
      after dosing.

PMID- 11966495
TI  - Hiatal hernia is the key factor determining the lansoprazole dosage required for
      effective intra-oesophageal acid suppression.
AB  - BACKGROUND: Effective intra-oesophageal acid suppression can be achieved with
      lansoprazole. The daily dosage could be influenced by the presence of hiatal
      hernia. AIM: To assess the lansoprazole daily dosage required to normalize
      oesophageal acid exposure in patients with and without hiatal hernia. METHODS:
      Fifty patients with complications or atypical manifestations of gastro
      oesophageal reflux disease were given lansoprazole, 30 mg once daily. Three to
      four weeks after the start of treatment, patients underwent oesophageal pH
      monitoring while on therapy. If the results were still abnormal, the lansoprazole
      dosage was doubled and 24-h pH-metry was repeated 20-30 days thereafter. RESULTS:
      A 30-mg daily dosage of lansoprazole normalized oesophageal acid exposure in 70%
      of cases, whilst a 60-mg daily dosage was necessary in the remainder: the two
      groups differed only in the presence of hiatal hernia (28% vs. 100%,
      respectively; P=0.000). Effective intra-oesophageal acid suppression was obtained
      in all 25 patients without hiatal hernia with the 30-mg daily dosage of
      lansoprazole. CONCLUSIONS: Hiatal hernia is the key factor determining the
      lansoprazole dosage required for effective intra-oesophageal acid suppression in
      complicated and atypical gastro-oesophageal reflux disease. High efficacy of a 30
      mg daily dosage of lansoprazole can be predicted in the absence of hiatal hernia.

PMID- 11966494
TI  - A modification of the quininium resin test for assessing gastric acidity.
AB  - BACKGROUND: Gastric acid is an important defence against enteric infection.
      Studies investigating the relationship between hypochlorhydria and enteric
      infections or gastric malignancy have been limited by difficulties in the non
      invasive measurement of gastric acidity. AIM: To develop a blood test for
      hypochlorhydria based on the quininium resin test. METHODS: Quininium resin
      dissociates to liberate free quinine at pH <or= 3.5. Ten fasting adult volunteers
      ingested 100 mg/kg of quininium resin twice: once before (control) and once after
      acid suppression with rabeprazole (10 mg b.d. for 3 days). Blood and serum
      samples were collected at baseline and 45, 60, 75, 90 and 120 min after
      ingestion. Quinine levels were measured fluorometrically from 100 microL samples
      after simple extraction. Results obtained by the quininium resin test were
      compared with gastric juice pH measurements. RESULTS: After quininium resin
      ingestion, mean quinine levels were lower in the acid-suppressed than in the
      control condition at all times (P < 0.001). Optimized cut-off values at 90 min
      post-ingestion yielded 95% accuracy rates in both serum and blood. Quininium
      resin was well tolerated. CONCLUSIONS: Using blood or serum, the quininium resin
      test identifies hypochlorhydria accurately and non-invasively. This test may be
      useful in screening for gastric atrophy and in studies investigating
      hypochlorhydria.

PMID- 11966496
TI  - Corpus gastritis in patients with endoscopic diagnosis of reflux oesophagitis and
      Barrett's oesophagus.
AB  - BACKGROUND: A high level of gastric acid secretion is considered to be a risk
      factor for reflux oesophagitis or Barrett's oesophagus. Corpus gastritis may have
      a protective effect on the oesophagus, because of decreased gastric acid output.
      AIM: To determine if corpus gastritis is associated with reflux oesophagitis or
      Barrett's oesophagus. METHODS: Three antral and two corpus biopsies were taken
      from consecutive patients in whom Helicobacter pylori testing was requested
      during endoscopy at a single centre between January 1995 and May 1997. Antral and
      corpus gastritis was studied by histology; H. pylori was studied by histology,
      culture and CLO test. A regression model was used to test for correlation between
      reflux oesophagitis, Barrett's oesophagus and risk factors. RESULTS: During the
      study period, 676 patients had biopsies taken during upper gastrointestinal
      endoscopy. Endoscopic signs of reflux oesophagitis and Barrett's oesophagus were
      observed in 125 and 23 patients, respectively. Corpus gastritis was found in 59%
      of patients without reflux oesophagitis or Barrett's oesophagus, 45% of patients
      with reflux oesophagitis and 30% of patients with Barrett's oesophagus. Two
      hundred and fifty-seven patients underwent follow-up endoscopy after H. pylori
      therapy. During a mean follow-up of 3 months, the incidence of reflux
      oesophagitis was not statistically different for patients with healing of corpus
      gastritis (10/98; 10%) and patients with persistent gastritis (8/97; 8%).
      CONCLUSIONS: Corpus gastritis was less common in patients with an endoscopic
      diagnosis of reflux oesophagitis or Barrett's oesophagus.

PMID- 11966497
TI  - Comparison of the main oesophageal pathophysiological characteristics between
      short- and long-segment Barrett's oesophagus.
AB  - AIM: To assess the oesophageal manometric characteristics and 24-h pH profiles of
      patients with both short-segment and long-segment Barrett's oesophagus and
      compare them with those of patients with reflux oesophagitis and controls.
      METHODS: Seventy-nine patients who had undergone upper digestive endoscopy were
      recruited: 16 had short-segment Barrett's oesophagus, 13 had long-segment
      Barrett's oesophagus, 25 had grade III oesophagitis according to the Savary
      Miller classification and 25 were used as controls. The diagnosis of Barrett's
      oesophagus was based on the histological detection of specialized intestinal
      metaplasia, which extended < 3 cm into the oesophagus in patients with short
      segment disease and > 3 cm in patients with long-segment disease. All subjects
      underwent oesophageal manometry and basal 24-h oesophageal pH monitoring.
      RESULTS: The lower oesophageal sphincter pressure was significantly lower in
      patients with reflux oesophagitis and short-segment and long-segment Barrett's
      oesophagus than in controls (P=0.0004-0.0001), but there was no difference among
      the three reflux groups. The peristaltic wave amplitude of patients with long
      segment Barrett's oesophagus was significantly lower than that of controls
      (P=0.002) and patients with short-segment Barrett's oesophagus (P=0.02), but was
      no different from that of patients with reflux oesophagitis. The percentage of
      non-propagated wet swallows was significantly higher in patients with reflux
      oesophagitis and short-segment and long-segment Barrett's oesophagus when
      compared with that of controls (P=0.0004-0.0001). The total percentage of time
      the oesophagus was exposed to pH < 4.0 was significantly higher in patients with
      reflux oesophagitis and short-segment and long-segment Barrett's oesophagus
      (P=0.0001) than in controls, and was higher in patients with long-segment disease
      than in those with short-segment disease (P=0.01). CONCLUSIONS: Long-segment
      Barrett's oesophagus is characterized by a greater impairment of peristaltic wave
      amplitude and a higher oesophageal acid exposure than is short-segment Barrett's
      oesophagus. However, both forms are linked to increased acid reflux.

PMID- 11966498
TI  - Ranitidine, 75 mg, over-the-counter dose: pharmacokinetic and pharmacodynamic
      effects in children with symptoms of gastro-oesophageal reflux.
AB  - BACKGROUND: The use of over-the-counter antacids has increased in children under
      the age of 12 years, and has been followed by an apparent increase in the use of
      over-the-counter histamine-2 receptor antagonists. However, the pharmacokinetic
      and pharmacodynamic effects of over-the-counter histamine-2 receptor antagonists
      in the paediatric population are largely unknown. AIM: To evaluate the
      pharmacokinetics and pharmacodynamics of a single dose of the over-the-counter
      histamine-2 receptor antagonist, ranitidine, 75 mg, in children with symptoms of
      gastro-oesophageal reflux disease. METHODS: Children aged between 4 and 11 years
      with symptoms of heartburn suspected to be due to gastro-oesophageal reflux
      disease were recruited at six clinical centres. Following a single dose of either
      oral ranitidine, 75 mg (n=19), or placebo (n=10), recording of intragastric pH
      and serial blood sampling were carried out for 6 h. RESULTS: The estimated
      pharmacokinetic parameters of ranitidine, 75 mg, were as follows: the median Cmax
      value of 477 ng/mL occurred within a median of 2.5 h after dosing, and the median
      half-life was 2.0 h. The intragastric pH began to rise approximately 30 min after
      dosing with ranitidine to a peak of pH; 4. The pH in the ranitidine group
      remained higher than that in the placebo group throughout the 6-h evaluation
      period. Adverse events were generally mild. CONCLUSIONS: Ranitidine, 75 mg,
      significantly increased the intragastric pH in children aged 4-11 years. The
      pharmacokinetic and pharmacodynamic profiles were similar to those in adults.
      Ranitidine, 75 mg, appears to be effective for the control of intragastric
      acidity for 5-6 h in children aged 4-11 years.

PMID- 11966499
TI  - Four-week open-label trial of metronidazole and ciprofloxacin for the treatment
      of recurrent or refractory pouchitis.
AB  - BACKGROUND: Preliminary data suggest that short-term antibiotic therapy with a
      single drug is effective for the treatment of patients with pouchitis. However,
      some patients are resistant to treatment. AIM: To evaluate the therapeutic
      efficacy of a prolonged course of a combination of two antibiotics in patients
      with refractory or recurrent pouchitis, as well as its impact on their quality of
      life. METHODS: Patients with active refractory or recurrent pouchitis were
      recruited. This was defined as both: (i) a history of pouchitis at least twice in
      the last 12 months or persistent pouchitis requiring continual intake of
      antibiotics; and (ii) a Pouchitis Disease Activity Index score 3 7 (best to worst
      pouchitis=0-18) at the beginning of therapy. Treatment consisted of a combination
      of metronidazole, 400 or 500 mg twice daily, and ciprofloxacin, 500 mg twice
      daily, for 28 days. Symptomatic, endoscopic and histological evaluations were
      undertaken before and after antibiotic therapy using the Pouchitis Disease
      Activity Index score. Remission was defined as a combination of a Pouchitis
      Disease Activity Index clinical score of <or= 2, endoscopic score of <or= 1 and
      total score of <or= 4. The quality of life was assessed with the Inflammatory
      Bowel Disease Questionnaire, which encompasses bowel, systemic and emotional
      symptoms as well as social function (worst to best=32-224). RESULTS: Forty-four
      patients (24 male, 20 female; median age, 37.5 years) entered the trial and
      completed treatment. Thirty-six (82%) went into remission. The median Pouchitis
      Disease Activity Index scores before and after therapy were 12 (range, 8-17) and
      3 (range, 1-10), respectively (P < 0.0001). The median Inflammatory Bowel Disease
      Questionnaire score also significantly improved from 96.5 (range, 74-183) to 175
      (range, 76-215) with this therapy (P < 0.0001). The eight patients (five male,
      three female) who did not go into remission were significantly older (median 47.5
      vs. 35 years; P=0.007), had a longer history of pouchitis (95.5 vs. 26 months;
      P=0.0008), had a greater proportion with chronic pouchitis (chronic/relapsing:
      6/2 vs. 9/27; relative risk, 1.6; 95% confidence interval, 1.0-2.4) and tended to
      have a higher Pouchitis Disease Activity Index score before treatment (median
      14.5 vs. 12; P=0.13) than those who went into remission. Even in these eight
      patients, the median Pouchitis Disease Activity Index score significantly
      improved from 14.5 (range, 8-16) to 9.5 (range, 7-10) (P=0.0078), as did the
      Inflammatory Bowel Disease Questionnaire score from 95.5 (range, 74-134) to 127
      (range, 76-187) (P=0.039). The Inflammatory Bowel Disease Questionnaire score
      strongly correlated with the Pouchitis Disease Activity Index score (r=0.79, P <
      0.0001), and was significantly related to the patients' overall assessment of
      satisfaction (P < 0.0001). No serious side-effects were noted. CONCLUSIONS: Four
      week treatment with a combination of metronidazole and ciprofloxacin is highly
      effective in patients with active recurrent or refractory pouchitis, objectively
      improving the inflammation and quality of life. The Inflammatory Bowel Disease
      Questionnaire is a sensitive tool for evaluating patients with pouchitis, and
      correlates well with disease activity.

PMID- 11966501
TI  - Does withholding aspirin for one week reduce the risk of post-sphincterotomy
      bleeding?
AB  - BACKGROUND: Complications of endoscopic sphincterotomy are closely related to the
      endoscopic technique. To date, there have been no studies to indicate that
      aspirin increases the risk of bleeding after endoscopic sphincterotomy. AIM: To
      compare the incidence of post-sphincterotomy bleeding in patients with and
      without prior aspirin therapy. METHODS: Eight hundred and four patients were
      recruited into this retrospective study: 124 patients continued to take aspirin
      until the day of sphincterotomy (Group 1), 116 patients had their aspirin
      discontinued for 1 week before sphincterotomy (Group 2) and 564 patients had
      never taken aspirin (Group 3). The primary outcome analysed was the incidence of
      post-sphincterotomy bleeding. RESULTS: Sixty-seven patients (8.3%) developed post
      sphincterotomy bleeding. The incidences of post-sphincterotomy bleeding in Groups
      1, 2 and 3 were 9.7%, 9.5% and 3.9%, respectively. Group 1 showed significantly
      increased post-sphincterotomy bleeding when compared with Group 3 (P=0.01), and
      the risk was also significantly increased when Group 2 was compared with Group 3
      (P=0.01). However, there was no significant difference in post-sphincterotomy
      bleeding between Groups 1 and 2 (P=0.96). CONCLUSIONS: Aspirin therapy increased
      the risk of post-sphincterotomy bleeding. Withholding aspirin for 1 week before
      endoscopic sphincterotomy did not seem to decrease the risk of post
      sphincterotomy bleeding.

PMID- 11966500
TI  - Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with
      or without fluoride.
AB  - BACKGROUND: Previous data have indicated low bone formation as a mechanism of
      osteoporosis in inflammatory bowel disease. Fluoride can stimulate bone
      formation. AIM: To assess the effect of fluoride supplementation on lumbar spine
      bone mineral density in osteoporotic patients with inflammatory bowel disease
      treated in parallel with calcium and vitamin D. METHODS: In this prospective,
      randomized, double-blind, parallel and placebo-controlled study, 94 patients with
      inflammatory bowel disease (lumbar spine T score below - 2 standard deviations,
      normal serum 25OH vitamin D), with a median age of 35 years, were included. Bone
      mineral density was measured by dual-energy X-ray absorptiometry. Patients were
      randomized to receive daily either sodium monofluorophosphate (150 mg, n=45) or
      placebo (n=49) for 1 year, and all received calcium (1 g) and vitamin D (800 IU).
      The relative change in bone mineral density from 0 to 12 months was tested in
      each group (fluoride or placebo) and compared between the groups. RESULTS: Lumbar
      spine bone mineral density increased significantly in both groups after 1 year:
      4.8 +/- 5.6% (n=29) and 3.2 +/- 3.8% (n=31) in the calcium-vitamin D-fluoride and
      calcium-vitamin D-placebo groups, respectively (P < 0.001 for each group). There
      was no difference between the groups (P=0.403). Similar results were observed
      according to corticosteroid intake or disease activity. CONCLUSIONS: Calcium and
      vitamin D seem to increase lumbar spine density in osteoporotic patients with
      inflammatory bowel disease; fluoride does not provide further benefit.

PMID- 11966502
TI  - Safety and efficacy of two reduced dosing regimens of sodium phosphate tablets
      for preparation prior to colonoscopy.
AB  - OBJECTIVES: To evaluate the safety and efficacy of two reduced dosing regimens of
      sodium phosphate tablets (Visicol, InKine Pharmaceutical Co. Inc., Blue Bell, PA,
      USA) for colon cleansing prior to colonoscopy. METHODS: In a randomized,
      multicentre, endoscopist-blinded clinical study, adults undergoing colonoscopy
      received either 28 tablets (42 g) or 32 tablets (48 g) of sodium phosphate for
      colon cleansing. The endoscopist used a validated four-point scale to rate the
      overall quality of colon cleansing, as well as cleansing in the ascending colon.
      Adverse events were collected and evaluated. RESULTS: The quality of overall
      colon cleansing was 'excellent' or 'good' in 84% or more of both groups, with no
      significant difference between the two doses. No patient had a preparation rated
      as 'inadequate' or required a repeat procedure. All patients were able to
      complete the assigned dose of tablets, and there were no deaths, serious adverse
      events or dropouts from the study. CONCLUSIONS: A reduced tablet regimen for
      sodium phosphate tablets, using either 28 or 32 tablets, is well tolerated and
      effective for colon cleansing prior to colonoscopy.

PMID- 11966503
TI  - Acute effect of clonidine on gastric emptying in patients with diabetic
      gastropathy and controls.
AB  - BACKGROUND: The treatments available for diabetic gastropathy are frequently
      ineffective. Clinical observations suggest that clonidine, an a-2 adrenergic
      agonist, may improve diabetic gastropathy symptoms. AIMS: To establish whether a
      single oral dose of clonidine alters the gastric emptying of a solid meal in 10
      patients with diabetic gastropathy and their matched controls. A secondary goal
      was to compare two methods of analysis of the data from gastric emptying studies.
      METHODS: Clonidine, 0.3 mg, or a matched placebo were administered orally in a
      double-blind fashion. RESULTS: Only three of the 10 patients showed an increased
      gastric residual volume. Gastric emptying rates were comparable in patients and
      controls. Clonidine had no significant effect on gastric emptying in the controls
      but increased t1/2 values in the patient group. This effect just reached
      statistical significance only when calculated by the power exponential method
      (P=0.05 but not by the linear component model. CONCLUSIONS: Delayed gastric
      emptying is not an invariable characteristic of symptomatic diabetic gastropathy.
      Clonidine, given as a single dose of 0.3 mg orally, has no gastric prokinetic
      effects. It may act on gastric afferent innervation or, more likely, at a central
      site to reduce nausea and vomiting. The analysis of gastric emptying data by the
      power exponential and the two linear component methods yields equivalent results.

PMID- 11966504
TI  - Domperidone is more effective than cisapride in children with diabetic
      gastroparesis.
AB  - BACKGROUND: Disorders of gastrointestinal motility are commonly detected in
      patients with insulin-dependent diabetes mellitus and are associated with
      significant morbidity. They contribute to poor metabolic control of diabetes.
      AIM: To assess the effect of an 8-week course of domperidone or cisapride on
      gastric electrical activity, gastric emptying time and dyspeptic symptoms in
      children with insulin-dependent diabetes mellitus and gastroparesis. METHODS:
      Dyspeptic symptoms were assessed by a score system, gastric emptying time was
      measured by ultrasonography and gastric electrical activity was obtained by
      electrogastrography. Fourteen children received domperidone and 14 received
      cisapride. The median (range) ages were 11.6 years (5-15 years) and 12 years (6
      16.9 years), respectively. Symptom assessment, ultrasonography and
      electrogastrography were repeated at the end of the trial. Fasting and fed (180
      min after feeding) glycaemia and haemoglobin A, C (HbA1c) levels were also
      measured. RESULTS: At the end of the trial both groups showed a significant
      decrease in symptomatic score; however, the score was markedly lower in the
      domperidone group than in the cisapride group (P < 0.01). Domperidone was
      significantly more effective than cisapride in reducing the gastric emptying time
      (P < 0.05), normalizing gastric electrical activity (P < 0.05) and decreasing the
      prevalence of episodes of gastric dysrhythmia (P < 0.01). Domperidone was also
      more effective than cisapride in improving diabetic metabolic control. No
      potentially drug-related adverse effects occurred. CONCLUSIONS: In children with
      insulin-dependent diabetes mellitus complicated by dyspeptic symptoms and
      gastroparesis, domperidone is superior to cisapride in reversing gastric emptying
      delay and gastric electrical abnormalities, as well as in improving dyspeptic
      symptoms and diabetic metabolic control.

PMID- 11966505
TI  - Dose finding study of mosapride in functional dyspepsia: a placebo-controlled,
      randomized study.
AB  - BACKGROUND: Prokinetic agents have shown variable efficacy in the treatment of
      functional dyspepsia. Mosapride is a new prokinetic 5-hydroxytryptamine-4
      agonistic agent. AIM: To evaluate the efficacy of three dosage regimens of
      mosapride compared with placebo in the treatment of functional dyspepsia.
      METHODS: Patients were randomly allocated to treatment with placebo or mosapride
      (5 mg b.d., 10 mg b.d. or 7.5 mg t.d.s.) in a double-blind, prospective,
      multicentre, multinational study. The change in symptom severity score from an
      untreated baseline week to the sixth week of treatment was used to compare
      treatment efficacy. RESULTS: There were 141, 140, 143 and 142 patients valid for
      evaluation in the intention-to-treat population in the placebo, mosapride 5 mg
      b.d., mosapride 10 mg b.d. and mosapride 7.5 mg t.d.s. groups, respectively. The
      mean changes in the overall dyspeptic symptom score were - 0.90, - 0.94, - 0.88
      and - 0.89, respectively, and the proportions of patients feeling better at the
      end of the treatment period were 60%, 59%, 59% and 61%, respectively. No
      statistically significant difference was seen. CONCLUSIONS: Treatment of
      functional dyspepsia with mosapride was not superior to placebo. The result
      raises the question of whether treatment with prokinetic agents is appropriate
      for functional dyspepsia.

PMID- 11966506
TI  - Perceived food and drug allergies in functional and organic gastrointestinal
      disorders.
AB  - BACKGROUND: Gastrointestinal symptoms are often due to functional disorders. Many
      individuals with abdominal symptoms believe they are allergic to or intolerant of
      various foods. AIM: To assess whether self-reported allergy is linked to a
      subsequent functional or organic diagnosis. METHODS: One thousand new patients
      attending a district hospital gastroenterology clinic completed a questionnaire
      about believed drug and food allergies and foodstuffs thought to worsen symptoms.
      No attempt was made to confirm patients' self-reported allergies or intolerances.
      Final diagnoses were classified as organic or functional. RESULTS: Nineteen per
      cent of patients reported drug allergies, 14% reported food allergies and 30%
      identified foods that worsened symptoms. Atopic patients reported more allergies.
      Forty-eight per cent of patients had a functional diagnosis. Women were twice as
      likely as men to have a functional diagnosis. Patients subsequently diagnosed
      with a functional disorder were more likely than those with organic disease to
      report drug allergies (odds ratio, 1.92; 95% confidence interval (CI), 1.39
      2.65), food allergies (odds ratio, 4.14; 95% CI, 2.73-6.26) or foods that
      worsened their abdominal symptoms (odds ratio, 3.08; 95% CI, 2.31-4.10). The
      likelihood of symptoms being functional increased even further if adverse
      reactions to both drugs and foods were reported. Patients with weight gain were
      more likely to report food allergy, and those with both features were very likely
      to have a functional disorder (odds ratio, 4.58; 95% CI, 3.08-6.86). CONCLUSIONS:
      Patients with gastrointestinal symptoms who report drug or food allergies or
      worsening of symptoms with various foods are more likely to have functional than
      organic illness. Enquiry about perceived allergies and intolerances may help in
      the early identification of functional gastrointestinal disorders.

PMID- 11966507
TI  - Extra-intestinal manifestations associated with irritable bowel syndrome: a twin
      study.
AB  - BACKGROUND: Little is known about the role of genetic and environmental factors
      in irritable bowel syndrome. Various extra-intestinal manifestations are more
      prevalent in cases than in controls. Genetic effects may be important in the
      liability to develop functional bowel disorders. AIMS: To evaluate the
      associations of irritable bowel syndrome with several disorders co-morbid with
      the condition, using both a case-control design and a co-twin control design.
      METHODS: A sample of 850 Swedish twin pairs, aged 18-85 years, was contacted for
      a telephone interview. Through a diagnostic algorithm, 72 unrelated cases of
      irritable bowel syndrome and 216 age- and gender-matched controls were
      identified. Fifty-eight twin pairs discordant for irritable bowel syndrome were
      evaluated in co-twin analyses. RESULTS: Renal problems (odds ratio (OR)=3.3;
      confidence interval (CI), 1.3-8.2), obesity (OR=2.6; CI, 1.0-6.4), underweight in
      the past (OR=2.4; CI, 1.1-6.4), gluten intolerance (OR=9.0; CI, 1.4-60.1),
      rheumatoid arthritis (OR=3.2; CI, 1.1-9.4) and poor self-rated health (OR=1.8;
      CI, 1.0-3.2) were significantly associated with irritable bowel syndrome. In the
      co-twin analyses, the only factors maintaining significance were renal and
      recurrent urinary tract problems. CONCLUSIONS: The association between irritable
      bowel syndrome and renal and urinary tract problems does not reflect a genetic or
      familial mediation. Eating disorders in childhood represent a familial
      environmental influence on irritable bowel syndrome, whereas the association with
      rheumatoid arthritis and perhaps gluten intolerance probably reflects genetic
      mediation.

PMID- 11966508
TI  - Blood antioxidant levels in patients with alcoholic liver disease correlate with
      the degree of liver impairment and are not specific to alcoholic liver injury
      itself.
AB  - BACKGROUND: Enhanced production of reactive oxygen species may play a pathogenic
      role in alcoholic liver injury. AIMS: To investigate whether various antioxidant
      parameters in blood are affected in different stages of alcoholic liver disease
      and how specific the changes are relative to non-alcoholic cirrhosis. METHODS:
      Patients with alcohol abuse without cirrhosis (n=14), with alcoholic cirrhosis
      [Child-Pugh scores A (n=9), B (n=5) and C (n=18)] and with non-alcoholic
      cirrhosis [Child-Pugh score C (n=6)] and healthy controls (n=13) were studied.
      Levels of reduced glutathione and glutathione peroxidase activity in blood,
      erythrocytic superoxide dismutase activity and carotenoids, alpha-tocopherol and
      malondialdehyde in plasma were measured. RESULTS: Levels of reduced glutathione
      were significantly decreased in Child-Pugh score C cirrhotics, alcoholic or not
      in origin, whereas oxidized glutathione and glutathione peroxidase activity were
      not affected. Superoxide dismutase activity and alpha-tocopherol levels were not
      significantly different in the various groups. Carotenoid levels were
      significantly lower in alcoholic cirrhotics (Child-Pugh score C) vs. controls.
      Malondialdehyde levels were elevated only in cirrhotics Child-Pugh score C,
      alcoholic or non-alcoholic. CONCLUSIONS: Levels of reduced glutathione and
      malondialdehyde reflect the degree of liver impairment, more than the relation
      with alcohol intake. Decreases in several antioxidant levels are not specific to
      alcoholic liver injury.

PMID- 11966509
TI  - Effect of alosetron on left colonic motility in non-constipated patients with
      irritable bowel syndrome and healthy volunteers.
AB  - BACKGROUND: Alosetron is a 5-hydroxytryptamine-3 receptor antagonist reducing
      symptoms in female patients with diarrhoea-predominant irritable bowel syndrome,
      and is known to increase the colonic transit time. AIM: To study the effect of
      alosetron on left colonic phasic motility in ambulant non-constipated patients
      with irritable bowel syndrome and healthy volunteers. METHODS: In a double-blind,
      randomized, crossover design, 10 patients with irritable bowel syndrome and 12
      sex- and age-matched volunteers were treated for two 7-day periods with
      alosetron, 4 mg b.d., or placebo b.d. On day 6 of each treatment period, a six
      channel solid-state manometric catheter was positioned in the left colon and 24 h
      motility was studied on day 7. The periprandial phasic motility around dinnertime
      was evaluated in the descending and sigmoid colon. The high-amplitude propagated
      contraction frequency and characteristics were calculated. RESULTS: Alosetron
      appeared to increase the overall periprandial frequency in the sigmoid colon
      (P=0.043) and the mean amplitude of colonic contractions in the descending colon
      (P=0.007). The high-amplitude propagated contraction frequency was higher on
      alosetron during the second half of the day for patients with irritable bowel
      syndrome (P=0.002), with increased mean propagation length of high-amplitude
      propagated contractions (P=0.001). The stool frequency (P=0.024) and stool
      consistency score (P=0.002) were decreased by alosetron. CONCLUSIONS: The 5
      hydroxytryptamine-3 receptor antagonist alosetron marginally increased left
      colonic periprandial phasic motility. Alosetron increased the number and
      propagation length of high-amplitude propagated contractions, which were
      paradoxically accompanied by a decrease in stool frequency and a firming of stool
      consistency.

PMID- 11966510
TI  - General principles to enhance practice patterns in gastrointestinal endoscopy.
AB  - AIM: To develop general rules on how to pursue a therapeutic goal of
      interventional endoscopy without getting lost in abundant details. METHODS: The
      influences of various medical interventions on the survival of a patient with
      gastrointestinal haemorrhage are modelled by an influence diagram. Survival is
      the focal point of multiple influences affecting its overall strength. Any
      downstream influence can represent the focal point of other preceding upstream
      influences. The mathematics underlying the influence diagram are similar to those
      of a decision tree with some notable exceptions. Its formalism allows one to
      consider inhibitory and additive influences and to include in the same analysis
      non-commensurable qualities, such as correct diagnosis, haemostasis or survival.
      RESULTS: The analysis reveals five general rules. First, the large number of
      factors involved in successful endoscopy render the influence of each individual
      factor less important. Second, a single factor that exerts its influence on many
      subsequent factors tends to be associated with an overall greater relevance.
      Third, remote influences are of lesser relevance than those directly linked to
      the final outcome. Fourth, factors multiplied by several consecutive
      probabilities lose their influence. Fifth, endoscopists need to assess the
      relevance of individual factors with respect to the immediate goals of endoscopy,
      as well as the general goals of patient well-being. CONCLUSIONS: The influence
      model of endoscopic haemostasis reveals several general principles that can be
      utilized as tools in endoscopy training.

PMID- 11966511
TI  - Prospective audit of gastroscopy under the 'three-day rule': a regional
      initiative in Italy to reduce waiting time for suspected malignancy.
AB  - BACKGROUND: A regional initiative, called the 'three-day rule', has recently been
      introduced in Italy to facilitate the earlier diagnosis of malignancy. It
      requires patients with suspected severe diseases to have a diagnostic procedure
      performed within three working days of referral by a general practitioner. AIM:
      To assess prospectively the effectiveness and compliance with the three-day rule
      for upper digestive malignancies. METHODS: We compared patients referred for
      gastroscopy under the three-day rule initiative with contemporaneous open access
      referrals over a 12-month period at a single large teaching hospital in west
      Milan. We compared the prevalence of malignancies and other serious non
      neoplastic diseases as well as the waiting times in the two groups. The
      appropriateness of the indications for each referral was also reviewed by a
      gastroenterologist blind to the outcome of the test. RESULTS: One hundred and
      forty-two patients referred for gastroscopy under the three-day rule scheme and
      767 routine referrals were studied. Significantly more oesophageal/gastric
      cancers (6% vs. 1%) and serious benign gastrointestinal lesions (grade II-III
      oesophagitis or peptic ulcer) were diagnosed in three-day rule patients in
      comparison with routine referrals (P < 0.05). The rate of inappropriate referral
      was significantly lower in the three-day rule group than in the open access group
      (39% vs. 22%) (P < 0.01). The estimated cost of the three-day rule scheme (in
      extra list examinations alone) was 10 780 euros, with about 1198 euros per
      diagnosis of cancer, but only 229.5 euros per 'useful' diagnosis (including
      peptic ulcer disease and oesophagitis). CONCLUSIONS: Significantly more upper
      gastrointestinal cancers and serious benign diseases can be found within a short
      period to comply with the three-day rule scheme. However, some general
      practitioners appear to over-interpret alarm symptoms, leading to some
      inappropriate referrals. Better awareness of appropriate urgent referral criteria
      is needed in order to ensure that the best use is made of the resources
      available.

PMID- 11966512
TI  - Helicobacter pylori infection, anti-cagA antibodies and peptic ulcer: a case
      control study in Italy.
AB  - AIM: To evaluate the association between infection with specific strains of
      Helicobacter pylori and peptic ulcer in patients referred for upper
      gastrointestinal endoscopy. METHODS: One thousand, six hundred and twenty-six
      consecutive dyspeptic patients, referred to one Endoscopy Unit in Bologna, Italy,
      were enrolled. For each participant, a blood sample was obtained for the
      measurement of distinct immunoglobulin G antibodies against H. pylori lysate and
      cytotoxin associated gene A (cagA). A case-control study included the whole
      series: patients diagnosed with duodenal (n=275) or gastric (n=71) ulcer were
      identified and independently compared with controls with non-ulcer dyspepsia
      (n=1280). RESULTS: H. pylori seroprevalence (at least one positive marker) was
      associated with increasing age, male sex and a diagnosis of peptic ulcer. This
      association was stronger with duodenal ulcer (multivariate odds ratio (OR), 5.2;
      95% confidence interval (CI), 3.5-7.9) than with gastric ulcer (OR, 2.3; 95% CI,
      1.2-4.4). Further analyses showed that H. pylori lysate+/cagA- subjects had a
      moderately increased risk of duodenal (OR, 3.2), but not gastric (OR, 1.1),
      ulcer. When cagA+ subjects were separately compared with seronegative patients,
      there was a six-fold increased risk for duodenal ulcer and a three-fold increased
      risk for gastric ulcer. CONCLUSIONS: A strong positive association between
      infection with a cagA+ H. pylori strain and the presence of peptic disease was
      found. The seroprevalence of anti-cagA antibodies among patients with non-ulcer
      dyspepsia is so high (41%) to preclude its use as a pre-endoscopic screening
      test.

PMID- 11966513
TI  - P-glycoprotein-170 inhibition significantly reduces cortisol and ciclosporin
      efflux from human intestinal epithelial cells and T lymphocytes.
AB  - AIM: To assess the role of P-glycoprotein-170 (P-gp) in transporting cortisol and
      ciclosporin from human intestinal epithelium and T lymphocytes. METHODS: The
      effect of P-gp inhibitors (verapamil, 0-100 microM; PSC 833, 0-20 microM) on the
      intracellular accumulation of 3H-cortisol and 3H-ciclosporin was studied in
      confluent layers of human Caco-2 cells (n=6), a P-gp-dependent absorptive
      intestinal epithelial cell phenotype, and moderately resistant MDRhigh CEM/VBL
      100 T cells (n=6). The transport of 3H-vinblastine, a strong multidrug resistance
      (MDR) substrate, and 3H-progesterone, a poor MDR substrate, was also studied.
      RESULTS: Caco-2 cells had a 2.4-, 6.6-, 6.7- and 1.03-fold higher net basal to
      apical transport (efflux) of 3H-cortisol, 3H-ciclosporin, 3H-vinblastine and 3H
      progesterone, respectively. PSC 833 (20 microM) reduced cortisol efflux by 69%
      (0.23 +/- 0.04 to 0.07 +/- 0.01 pmol/cm2/h, P < 0.05) and ciclosporin efflux by
      76% (11.1 +/- 1.4 to 2.7 +/- 0.6 pmol/cm2/h, P < 0.001). MDRlow CEM T cells had a
      1.4-, 1.9-, 3.2- and 1.02-fold higher intracellular accumulation of cortisol,
      ciclosporin, vinblastine and progesterone than MDRhigh CEM/VBL 100 T cells.
      Increasing concentrations of PSC 833 (> 0.1 microM) and verapamil (> 1 microM)
      restored the intracellular level of 3H-cortisol and 3H-ciclosporin in MDRhigh
      CEM/VBL 100 T cells to that of MDRlow CEM cells with little change in
      accumulation in the MDRlow parental cell line. CONCLUSIONS: P-gp inhibitors
      significantly increase intracellular cortisol and ciclosporin levels in human
      intestinal epithelium and T lymphocytes in a dose-dependent manner, demonstrating
      a potential mechanism for overcoming poor response to immunosuppressant therapy
      in refractory inflammatory bowel disease.

PMID- 11966514
TI  - Continued utilization and costs of proton pump inhibitors after Helicobacter
      pylori eradication in chronic users of gastrointestinal drugs.

PMID- 11966518
TI  - Gastrin interferes with the differentiation of gastric pit cells and parietal
      cells.
AB  - BACKGROUND: Gastrin is known to have stimulatory effects on gastric mucosa;
      however, long-term effect of gastrin stimulation is not well known. AIM AND
      METHODS: To investigate the long-term effect of hypergastrinaemia, we established
      hypergastrinaemic transgenic mice by introducing a mutated human gastrin gene.
      Homozygously transgene-expressing mice showed serum gastrin levels of more than
      600 pg/mL. RESULTS: Neither progastrin nor glycine-extended gastrin titre
      elevation were observed in hypergastrinaemic transgenic mice. Stomachs from the
      30-35-week-old transgenic mice were 30-50% heavier and their mucosa were markedly
      thicker than those of the controls. The hypertrophic gastric mucosa of
      hypergastrinaemic transgenic mice consisted of elongated pits with widespread
      proliferative zones, and comprised depleted glandular regions. In situ
      hybridization study indicated that expression of H, K-ATPase mRNA in parietal
      cells of hypergastrinaemic transgenic mice was markedly decreased. By gastrin
      binding assay in vivo, specific gastrin binding sites were observed in the mid
      glandular region of hypergastrinaemic transgenic mice that consisted mainly of
      prepit cells. CONCLUSIONS: These results suggest that long-term stimulation of
      gastrin increases the expression of CCK-B/gastrin receptors in the less
      differentiated pit cells that are the main component of elongated gastric units,
      and lessens the well-differentiated characteristics of parietal cells.

PMID- 11966519
TI  - Time-course changes of ECL cell markers in acetic acid-induced gastric ulcers in
      rats.
AB  - BACKGROUND AND AIM: Enterochromaffin-like (ECL) cells are the major source of
      histamine for the regulation of gastric acid secretion, and also contain
      histidine decarboxylase (HDC), vesicular monoamine transporter 2 (VMAT2), and
      chromogranin A (CgA). Although gastric acid secretion is suppressed during ulcer
      healing, the role of ECL cells in that process is not yet fully understood. In
      the present study, we investigated the changes in ECL cell number during healing
      of experimental ulcers in rats. MATERIALS AND METHODS: Seven-week-old male Wistar
      rats were used. Acetic acid-induced ulcers were caused by an application of 100%
      acetic acid to the serosal surface of the rat stomachs. At different time points
      following the induction (12 h-15 days), time-course changes of HDC, VMAT2, and
      CgA mRNA expression were investigated by Northern blot analysis. The expressions
      of HDC, VMAT2, and CgA were immunostained on gastric mucosal sections with
      ulcers. RESULTS: HDC, VMAT2, and CgA mRNA in gastric mucosa each showed an
      initial marked transient decrease, followed by an increase on day 10 back to the
      initial value. HDC, VMAT2, and CgA-immunoreactive cells at the ulcer margin were
      reduced in number on day 3, compared with those in distant areas. On day 10,
      however, they returned to levels similar to those in distant areas. CONCLUSION:
      The present study revealed a local down-regulation of HDC, VMAT2, and CgA in ECL
      cells at the ulcer margin. As a result, we concluded that a suppression of ECL
      cell activity during ulcer healing may be involved in suppressed gastric acid
      secretion.

PMID- 11966520
TI  - Inhibition of CN (protein phosphatase-2B) suppresses Ca2+-mediated acid secretion
      in rats.
AB  - BACKGROUND AND AIM: It has been suggested that CN (calcineurin, protein
      phosphatase-2B) regulates signal transduction, particularly in various secretory
      cells. In this study, we examined whether CN plays a role in stimulus-secretion
      coupling of gastric parietal cells. MATERIALS AND METHODS: Localization of CN in
      gastric epithelial cells was examined immunohistochemically. The role of CN in
      the acid secretion pathway of gastric parietal cells was assessed by evaluating
      the effect of FK506, a specific inhibitor of CN, on gastric acid secretion in
      pylorus-ligated rats. In addition, the effect of FK506 on secretagogue
      (carbachol, tetragastrin and histamine)-stimulated acid secretion was
      investigated in lumen-perfused rats. RESULTS: CN was specifically expressed in
      gastric parietal cells and chief cells of the gastric mucosal epithelium
      immunohistochemically. FK506 dose-dependently inhibited gastric acid secretion in
      pylorus-ligated rats. In lumen-perfused rats, FK506 completely inhibited acid
      secretion prestimulated by carbachol and tetragastrin, agonists known to increase
      cytosolic Ca2+, but did not affect acid secretion prestimulated by histamine.
      CONCLUSIONS: Our findings demonstrate that FK506 has a potent antisecretory
      effect in parietal cells through inhibition of only Ca2+-mediated acid secretion
      pathways. As FK506 is known to specifically inhibit CN, which plays an important
      role in signal transduction in various secretory cells, protein dephosphorylation
      signalling might also be crucial for gastrin and M3 muscarine receptor-mediated
      stimulation of proton pump.

PMID- 11966521
TI  - Circadian rhythm of melatonin and prostaglandin in modulation of stress-induced
      gastric mucosal lesions in rats.
AB  - BACKGROUND: We previously demonstrated the circadian variation of water-immersion
      restraint stress (WRS)-induced gastric mucosal lesions in rats. AIM: To
      investigate the roles of melatonin and prostaglandin in the gastric mucosa in
      circadian modulation of WRS. METHODS: Fasted rats were subjected to 4-h WRS
      during both the diurnal and nocturnal phases of a light/dark cycle. Mucosal
      lesions, serum melatonin concentrations, mucosal generation of prostaglandin E2
      (PGE2) and mucosal gene expressions of cyclooxygenase (COX)-1 and -2 were
      evaluated. RESULTS: Lesion area after 4-h stress during the dark phase was
      significantly smaller than that in light-phase controls. Serum melatonin
      concentration in control rats during the light phase was significantly increased
      4 h after WRS, but PGE2 generation was decreased by 48% as compared to that in
      intact mucosa before stress. In the dark phase, melatonin concentration after 4-h
      WRS was significantly depressed as compared with the control level at the
      corresponding time. PGE2 concentrations after 4-h WRS in the dark phase were not
      decreased compared with the control level at the corresponding time, although
      PGE2 level was significantly lower than that in light-phase controls. Expression
      of COX-1 and COX-2 mRNA was detected after exposure to stress in both the light
      and dark phases. CONCLUSION: These results suggest that circadian rhythm has an
      important role in the formation of stress-induced gastric mucosal lesions in
      rats. The circadian rhythm of melatonin responses and PGE2 generation may
      contribute to nocturnal/diurnal rhythmicity of gastric mucosal defences between
      day and night.

PMID- 11966522
TI  - Effect of taurine on ulcerogenic response and impaired ulcer healing induced by
      monochloramine in rat stomachs.
AB  - BACKGROUND: It is well known that neutrophil-derived hypochlorous acid interacts
      with ammonia (NH4OH) to generate monochloramine (NH2Cl) and that NH2Cl irritates
      the gastric mucosa and impairs ulcer healing. AIM: To examine the effect of
      taurine, a hypochlorous acid scavenger, on the mucosal ulcerogenic and the
      impaired healing response induced by NH2Cl in rat stomachs, in comparison with
      those of methionine and glycine. METHODS AND RESULTS: Under anaesthesia, oral
      administration of NH2Cl (120 mmol/L) produced severe lesions in male Sprague
      Dawley rat stomachs. Taurine (10-100 mg/kg) given p.o. 30 min prior to NH2Cl dose
      dependently prevented these lesions in response to NH2Cl. This action was
      mimicked by methionine (3-30 mg/kg) but not by glycine (10-100 mg/kg). Under
      urethane anaesthesia, mucosal exposure to NH4OH (120 mmol/L) caused a marked
      reduction of potential difference (PD) in the ex vivo chambered stomachs after
      induction of ischaemia, resulting in severe lesions. These ulcerogenic and PD
      responses by NH4OH plus ischaemia were also mitigated by taurine and methionine,
      but not glycine, applied to the chamber 20 min before the onset of NH4OH plus
      ischaemia. Moreover, oral administration of 100% ethanol produced severe
      haemorrhagic lesions in rat stomachs, all of which rapidly healed within 7 days
      after lesion induction. Daily administration of NH2Cl (20 mmol/L) significantly
      delayed the healing of these lesions, but recovery of this impaired healing
      response was obtained by concurrent administration of taurine. Both taurine and
      methionine showed a potent scavenging effect against NH2Cl in vitro. CONCLUSIONS:
      (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa
      and impairs the healing response; (2) taurine exerts a prophylactic effect
      against the deleterious effects of NH2Cl, mainly due to its scavenging action
      against NH2Cl; and (3) this effect of taurine may be useful for treatment of
      gastritis associated with Helicobacter pylori infection.

PMID- 11966523
TI  - Association between gastric myoelectrical activity and intraluminal nitric oxide.
AB  - BACKGROUND: We have previously shown that the intraluminal concentration of NO in
      H. pylori-positive patients is significantly reduced compared to that in H.
      pylori-negative patients. AIM: The aim of this study was to evaluate the effect
      of H. pylori infection on gastric motor activity in relation to the level of NO
      and nitrite in the stomach in humans. METHODS: Thirty-two H. pylori-negative and
      32 H. pylori-positive patients with dyspepsia were studied. Gastric myoelectrical
      activity was recorded for 24 h using surface electrogastrography. Intraluminal
      gas and juice were endoscopically collected from the stomach to determine NO and
      nitrite and nitrate (NOx) levels using a chemiluminescence system. RESULTS: The
      percentage of tachygastria in the morning preprandial state was significantly
      higher (P = 0.005) in H. pylori-positive than -negative patients. In H. pylori
      negative patients, there was a significant positive correlation between NO levels
      and the percentage of bradygastria (r = 0.56, P = 0.001) and a significant
      negative correlation between NOx levels and the percentage of normal electrical
      activity (r = - 0.57, P=0.001) in the preprandial state. CONCLUSIONS: Gastric
      motor activity is associated with NO and NOx levels in the gastric lumen. H.
      pylori infection may play a role in the pathogenesis of abnormal gastric
      myoelectrical activity.

PMID- 11966524
TI  - Increased expression of epidermal growth factor receptors in basal cell
      hyperplasia of the oesophagus after acid reflux oesophagitis in rats.
AB  - BACKGROUND: Epidermal growth factor (EGF), which binds to EGF receptors (EGF-R),
      stimulates oesophageal epithelial cell proliferation, enabling rapid repair after
      mucosal injury. In the normal human oesophageal epithelium, EGF-R expression is
      present and confined to the basal layer. AIM: To examine histological changes in
      and dynamics of EGF-R expression during healing after acid reflux oesophagitis in
      a rat model. METHODS: Gastric acid reflux oesophagitis was induced in Wistar rats
      by ligation of the pylorus and the transitional region between the forestomach
      and the grandular portion for 5 h, followed by release of both ligations. Rats
      were killed 7 and 14 days after production of oesophagitis to examine macroscopic
      and histological changes as well as dynamics of EGF-R expression. Epithelial cell
      proliferation was assessed by bromodeoxyuridine (BrdU) uptake, and expression of
      EGF-R mRNA and protein by RT-PCR and Western blotting or immunohistochemistry.
      RESULTS: Gastric acid reflux induced erosive and ulcerative mucosal lesions in
      the lower and middle part of the oesophagus. These lesions were healed by 14 days
      and histologically showed thickening of the oesophageal epithelium from 41.11 +/-
      3.09 microm in controls to 142.73 +/- 11.59 microm (P < 0.001) in ligated rats,
      as well as elongation of papillae and basal cell hyperplasia. The number of BrdU
      positive cells among basal cells on day 14 was significantly increased from 7.1
      +/- 0.8/field in controls to 30.9 +/- 3.0/field in ligated rats. Expression of
      EGF-R mRNA and protein was significantly increased on day 14 and most basal cells
      were immunohistochemically positive in both BrdU and EGF-R staining. CONCLUSION:
      Acid reflux-induced oesophageal injury caused basal cell hyperplasia with an
      increase in cell proliferation and EGF-R expression. Activation of EGF-R gene and
      protein in response to acid reflux-induced injury may facilitate mucosal healing.
      These results suggest that epidermal growth factor receptors play a crucial role
      in healing after acid reflux oesophagitis in rats.

PMID- 11966525
TI  - Ubiquitin-proteasome inhibitor enhances tumour necrosis factor-alpha-induced
      apoptosis in rat gastric epithelial cells.
AB  - BACKGROUND: Tumour necrosis factor (TNF-alpha) is a candidate factor for
      involvement in inflammation-mediated gastric mucosal injury. However, the effect
      of this cytokine on gastric epithelial cells has been poorly investigated. In the
      present study, we examined whether gastric epithelial cells are resistant to TNF
      alpha-induced apoptosis, and whether this resistance is related to ubiquitin
      proteasome-associated nuclear factor-kappaB (NF-kappaB) activation. METHODS: The
      rat gastric mucosal cell line RGM-1 was grown in DMEM/F12 medium supplemented
      with 10% FCS. Confluent monolayers of cells were pretreated or not for 60 min
      with PSI, a peptide aldehyde known to specifically inhibit the chymotrypsin-like
      activity of 26S proteasome. Cells were subsequently stimulated with recombinant
      rat TNF-alpha and their viability was determined by WST-1 assay. Apoptosis was
      confirmed by fluorescence microscopy after staining with Hoechst 33342 and
      propidium iodide, and DNA fragmentation was determined by flow cytometry using an
      APO-BRDU kit. IkappaB-alpha and the p65 binding subunit of NF-kappaB were
      detected by Western blots. RESULTS: Twenty-four-hour incubation with TNF-alpha
      alone or PSI alone did not affect the cell viability of RGM-1 cells. Pretreatment
      with PSI significantly enhanced the level of apoptosis induced by TNF-alpha. In
      RGM-1 cells treated with TNF-alpha, cytoplasmic IkappaB-alpha decreased and p65
      in nuclear extracts increased markedly 30 min after cytokine stimulation.
      Pretreatment with PSI at 12.5 micromol/L blocked these TNF-alpha-induced changes.
      CONCLUSION: PSI enhances TNF-alpha-induced apoptosis through inhibition of NF
      kappaB activation in RGM-1 cells.

PMID- 11966527
TI  - Gastric ulcerogenic responses following barrier disruption in knockout mice
      lacking prostaglandin EP1 receptors.
AB  - BACKGROUND/AIMS: Endogenous prostaglandins (PGs) are considered to play a pivotal
      role in maintaining the mucosal integrity of the stomach after injury. In the
      present study, we evaluated the mucosal ulcerogenic and mucosal blood flow (GMBF)
      responses in the stomach after damage by taurocholate (TC) in knockout mice
      lacking EP1 or EP3 receptors. METHODS: Under urethane anaesthesia, a mouse
      stomach was mounted in an ex vivo chamber, exposed to 20 mmol/L TC for 20 min and
      treated with 20 mmol/L HCl before and after TC. GMBF was measured with a laser
      Doppler flowmeter. RESULTS: Mucosal exposure to TC in wild-type mice caused a
      marked decrease in potential difference (PD), followed by an increase in H+ loss
      and GMBF. The decreased PD was gradually normalized after removal of TC from the
      chamber, with minimal damage in the mucosa 1 h after TC treatment. This
      hyperaemic response was inhibited by indomethacin, resulting in severe lesions in
      the mucosa without any change in PD or H+ loss. None of these responses induced
      by TC were altered in EP3-/- mice. However, in mice lacking EP1 receptors, TC
      treatment did not increase GMBF, despite causing PD reduction and acid loss, and
      resulted in severe damage in the mucosa. These responses were closely similar to
      those observed in animals pretreated with ONO-8711, a EP1 receptor antagonist.
      Mucosal PGE2 content was significantly increased after TC, similarly in all
      groups of mice. CONCLUSION: These results confirm a mediator role for PGE2 in
      gastric hyperaemic response following mucosal exposure to TC and suggest that
      endogenous PGs may contribute to maintaining mucosal integrity after barrier
      disruption, mainly through activation of the EP1 receptor subtype.

PMID- 11966526
TI  - Effect of PPARgamma ligands on the viability of gastric epithelial cells.
AB  - BACKGROUND: [corrected] Peroxisome proliferator-activated receptors (PPAR) are a
      family of three nuclear receptors (PPARalpha, PPARdelta, and PPARgamma). Although
      recent evidence suggests a role for PPARgamma in the regulation of colonic
      epithelial cell growth, the role for PPARgamma in the stomach has not been
      established. AIM: To examine the expression of PPARgamma and the effects of
      PPARgamma ligands on the viability of gastric epithelial cells. METHODS: MKN45
      cells and primary cultured rat gastric epithelial cells were used. Troglitazone
      (TGZ) and 15-deoxy-Delta12, 14-prostaglandin J2 (15d-PGJ2) were used as PPARgamma
      ligands. Expression of PPARgamma was examined by RT-PCR and Western blot
      analysis. Cell viability was measured by WST-1 assay and TUNEL assay was
      performed to detect apoptosis. RESULTS: MKN45 cells expressed all subtypes of
      PPAR. PPARgamma ligands decreased cell viability and induced cell death in a dose
      dependent manner, whereas ligands for PPARalpha and PPARdelta had no significant
      effect. TUNEL assay showed that this cell death is apoptosis. Primary cultured
      rat gastric epithelial cells also expressed PPARgamma and activation of PPARgamma
      decreased cell viability. CONCLUSION: These results suggest that PPARgamma plays
      an important role in the regulation of cell growth and cell death in gastric
      epithelial cells.

PMID- 11966528
TI  - Inhibition of proliferation of gastric epithelial cells by a cyclooxygenase 2
      inhibitor, JTE522, is also mediated by a PGE2-independent pathway.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) is one of the rate-limiting enzymes for
      prostaglandin synthesis from arachidonic acid. Although it is known that
      inhibition of cyclooxygenase activity delays ulcer healing, the regulatory
      relationship between COX-2 and its metabolites in gastric epithelial cell
      proliferation is not well known. AIM: To investigate whether COX-2 has an effect
      on gastric mucosal cell proliferation and further studied whether such effect is
      mediated only by prostaglandin E2 (PGE2), a representative metabolite of
      arachidonates in the gastric mucosa. METHODS: Artificial wounds of defined area
      size were created on complete monolayer cell sheets of isolated rat gastric
      epithelial cells and rat gastric cell line RGM1 under the addition of arachidonic
      acid or a COX-2 selective inhibitor, JTE522. Repair of wounds was assessed by
      monitoring wound size, with cell proliferation detected using 5-bromodeoxyuridine
      staining. Quantity of secreted PGE2 was measured by enzyme immunoassay. RESULTS:
      Stimulation of foetal calf serum increased the expression of COX-2 protein and
      inhibition of COX-2 retarded wound healing with reduction of cell proliferation.
      Arachidonic acid increased PGE2 production and accelerated restoration.
      Combination of JTE522 and arachidonic acid resulted in a marked retardation of
      wound healing compared to the control, but JTE522 did not completely suppress the
      increase in cellular PGE2 content following the addition of arachidonate.
      CONCLUSIONS: The difference in the effects of JTE522 on PGE2 production and on
      wound healing suggest that the involvement of COX-2 in gastric epithelial cell
      proliferation is not mediated solely by PGE2.

PMID- 11966530
TI  - Review article: COX-2, prostanoids and colon cancer.
AB  - Epidemiological, experimental, and clinical studies have demonstrated that colon
      carcinogenesis may be prevented by nonsteroidal anti-inflammatory drugs (NSAIDs).
      Although controversy remains, recent studies, including ours, have revealed that
      NSAIDs suppress colon carcinogenesis at the adenoma stage where cyclooxygenase-2
      (COX-2), a major molecular target in this action, is mainly expressed in
      interstitial cells but not in tumour cells. Therefore, it is unlikely that NSAIDs
      prevent colon cancer formation through modulating the functions of tumour cells.
      A more possible assumption is that NSAIDs suppress colon carcinogenesis through
      the inhibition of prostaglandin formation. However, the mechanisms by which
      prostanoids promote colon carcinogenesis have not been elucidated to date. A
      prostanoids act through both membrane receptors and nuclear receptors such as
      peroxisome proliferator receptor (PPAR) gamma or delta, one focus in this area is
      to investigate their roles in colon carcinogenesis, including the induction of
      growth factors.

PMID- 11966529
TI  - Up-regulation of COX-2 by inhibition of COX-1 in the rat: a key to NSAID-induced
      gastric injury.
AB  - BACKGROUND: A recent study demonstrated that inhibition of both cyclooxygenase
      (COX)-1 and COX-2 is required for the development of nonsteroidal anti
      inflammatory drug (NSAID)-induced gastric lesions. However, the role of COX-1 or
      COX-2 inhibition in the pathogenisis of these lesions remains unclear. AIM: To
      examine the gastric ulcerogenic properties of selective COX-1 and COX-2
      inhibitors in rats and to investigate further the relationship of COX inhibition
      to various events involved in the process of NSAID-induced gastric lesions.
      METHODS: Animals were given various COX inhibitors p.o., either alone or in
      combination, and killed 8 h later. Under the treatment, gastric damage,
      prostaglandin (PG) E2 content, mucosal permeability, myeloperoxidase (MPO)
      activity as well as gastric motility were examined. RESULTS: The nonselective COX
      inhibitor indomethacin inhibited PGE2 production, enhanced gastric motility, and
      provoked severe lesions in the stomach, with an increase in mucosal permeability
      and MPO activity. In contrast, the selective COX-2 inhibitor rofecoxib did not
      induce any damage in the stomach and had no effect on mucosal PGE2 content.
      Similarly, the selective COX-1 inhibitor SC-560 also caused no gastric damage,
      despite inhibiting PGE2 production. The combined administration of SC-560 and
      rofecoxib, however, provoked gross damage in the gastric mucosa, in a dose
      dependent manner for each drug. SC-560, but not rofecoxib, caused marked gastric
      hypermotility and an increase in mucosal permeability, although an increase in
      MPO activity was observed only when rofecoxib was coadministered. The normal
      gastric mucosa expressed COX-1 mRNA and not COX-2 mRNA, but COX-2 mRNA was
      expressed in the stomach after administration of SC-560 as well as indomethacin
      but not rofecoxib. CONCLUSION: These results suggest that the gastric ulcerogenic
      properties of NSAIDs are not accounted for solely by COX-1 inhibition, but
      require the inhibition of both COX-1 and COX-2. The inhibition of COX-1 up-
      regulates COX-2 expression, and COX-2/PGs may, in turn, counteract the
      deleterious affects of gastric hypermotility due to COX-1 inhibition.

PMID- 11966531
TI  - Wine stimulates gastric acid secretion in isolated rabbit gastric glands via two
      different pathways.
AB  - BACKGROUND & AIMS: Alcoholic beverages such as beer and wine are well known to
      potently stimulate gastric acid secretion, most probably through an increase in
      circulating gastrin level. The present study examined whether or not wine
      stimulates gastric acid secretion by a direct effect on parietal cells,
      enterochromaffin-like (ECL) cells or both. METHODS: Gastric mucosa was isolated
      from female Japanese white rabbits and gland specimens were prepared by the
      collagenase digestion method. Acid secretion was assessed by gland accumulation
      of [14C] aminopyrine. The effects of red wine, ethanol, non-alcoholic wine and
      drugs were determined by incubating gastric glands with aminopyrine.
      Radioactivity in solubilized glands was determined by a liquid scintillation
      counting. RESULTS: Neither wine nor ethanol (diluted 1 : 10(2) to 1 : 10(4)) had
      any effect on gastric acid secretion, whereas non-alcoholic wine stimulated acid
      secretion in a dose-dependent manner. All substances, however, significantly
      stimulated gastric acid secretion in IBMX (phosphodiesterase inhibitor)
      pretreated glands. S-0509 (a CCK-2 receptor antagonist) and atropine had no
      effect on acid secretion stimulated by wine, ethanol or non-alcoholic wine in
      IBMX-pretreated glands. Famotidine and omeprazole significantly inhibited the
      acid secretion resulting from all of the above stimulants. BAPTA (an
      intracellular Ca2+ chelator) inhibited acid secretion stimulated with wine or
      ethanol in a dose-dependent manner, but did not inhibit secretion stimulated by
      non-alcoholic wine. CONCLUSIONS: Wine was found to stimulate gastric acid
      secretion in gastric glands via two pathways, by an ethanol-induced increase in
      the concentration of intracellular Ca2+ in parietal cells, and by histamine
      release from ECL cells potentially induced by constituents present in wine.

PMID- 11966532
TI  - Conditional loss of TGF-beta signalling leads to increased susceptibility to
      gastrointestinal carcinogenesis in mice.
AB  - BACKGROUND: Downregulation of TGF-beta receptors is implicated in colon cancer
      development. Inactivation of either of the two transmembrane serine/threonine
      kinases, TGF-beta1 types I/II receptors, is now implicated in carcinogenesis,
      especially gastrointestinal carcinogenesis. METHODS: We generated transgenic
      mice, called pS2-dnRII or ITF-dnRII, of which the dominant negative mutant of the
      TGF-beta type II receptor was expressed under the control of tissue-specific
      promoters, the pS2 promoter for stomach and ITF for intestine. They were either
      infected with H.pylori (ATCC 43504 strain, CagA+ and VacA+) or administered with
      azoxymethane to determine the significance of loss of TGF-beta signalling in
      gastrointestinal carcinogenesis. RESULTS: Gastric adenocarcinoma developed in pS2
      dnRII mice, whereas only chronic active gastritis was noted in wild-type
      littermates after 36 weeks of H.pylori infection. Mice lacking in TGF-beta
      signalling specifically in the stomach showed a significantly higher
      proliferation cell nuclear antigen-labelling index when infected with H.pylori
      than wild-type littermates (P < 0.01). Development of colonic aberrant crypt foci
      was provoked in mice by intraperitoneal injections of azoxymethane, and ITF-dnRII
      mice showed significantly higher incidences of ACF and colon cancers than wild
      type littermates. CONCLUSIONS: Maintaining normal TGF-beta signalling in the
      gastrointestinal tract seems to be important either for preventing abnormal
      mucosal proliferation, or for suppressing or retarding carcinogenesis.

PMID- 11966533
TI  - The relationship between gastric cancer cells circulating in the blood and
      microsatellite instability positive gastric carcinomas.
AB  - BACKGROUND: Cancers characterized by microsatellite instability may be
      biologically different from their counterparts with stable microsatellite
      sequences. Circulating cancers cell present in blood prior to surgery may
      constitute an adverse prognostic finding. AIM: To correlate these two phenomena
      with morphological features and survival in advanced gastric cancer. METHODS: We
      examined 76 cases of resected sporadic, advanced gastric cancer by means of
      routine morphology and a panel of microsatellite markers. Sixty-six cases were
      screened for presence of cancer cells circulating in blood prior to the surgery
      using combined morphological and immunocytochemical approach. RESULTS: Twenty-one
      (27.6%) cases demonstrated microsatellite instability in at least one locus.
      Among them 11 (14.5%) showed microsatellite instability in more than 30% (4/12)
      examined loci, and they were therefore designated as replication error positive
      (RER+). Circulating cancer cells were detected in 2/19 microsatellite instability
      and in 11/47 remaining cases (difference not significant). The survival of the
      microsatellite instability cases was significantly better. The presence of
      circulating cancer cells did not correlate with survival. CONCLUSION: It is
      possible that the microsatellite instability status, but not circulating cancer
      cells, constitutes a prognostic predictive factor in advanced gastric carcinoma.
      Confirmation of this hypothesis requires continuation of patient follow-up.

PMID- 11966534
TI  - Detection of cancer cells in peripheral blood of stomach cancer patients using RT
      PCR amplification of tumour-specific mRNAs.
AB  - BACKGROUND: RT-PCR amplification of tumour-specific mRNA has been used for the
      detection of cancer cells in peripheral blood. AIM: To evaluate the
      characteristics of the tumour specific mRNA species in peripheral blood of
      stomach cancer patients. METHODS: We analysed CEA, GalNAc-T, MUC-1, c-MET and
      hTERT mRNA expression in the stomach cancer cell lines and tissues, lymph nodes
      and peripheral blood of stomach cancer patients using RT-PCR. RESULTS: In RT-PCR
      analysis of the peripheral blood, 4%, 8%, 21%, 46%, and 100% of stomach cancer
      patients were positive for CEA, GalNAc-T, c-MET, hTERT and MUC-1 mRNA,
      respectively, but MUC-1 mRNA was also positive in all normal blood samples. The
      detection of hTERT mRNA was correlated with poor differentiation (P = 0.01) and
      lymph node metastasis (P = 0.009). The presence of c-MET mRNA was correlated with
      T stage (P = 0.025), lymph node metastasis (P = 0.036), distant metastasis (P =
      0.031), and stage of the stomach cancer (P = 0.023). CONCLUSIONS: Our study
      suggest that hTERT mRNA in peripheral blood can be a molecular marker for gastric
      cancer. We also showed that each molecular marker can be correlated with the
      clinicopathological features of the patients.

PMID- 11966535
TI  - Screening of gene expression profiles in gastric epithelial cells induced by
      Helicobacter pylori using microarray analysis.
AB  - BACKGROUND: H. pylori infection is a major risk factor in gastric cancer
      development. The availability of cDNA microarrays creates the unprecedented
      opportunity to examine simultaneously dynamic changes of multiple pathways
      affected by H. pylori infection. AIM: In this study we examined broad patterns of
      gene expression induced by H. pylori in the gastric cancer cell line 1739-CRL AGS
      cells in culture using the U95A microarray. METHODS: H. pylori were cocultured
      with AGS cells for 4, 12, 24 and 48 h. Total RNA was extracted and after
      labelling was used for detection of genes represented in the human U95A
      microarray set. Data analyses were performed using GeneChip and CLUSFAVOR
      software. RESULTS: Nearly 6000 genes present in the array were expressed by AGS
      cells. We report approximately 200 genes that showed the most marked changes. Our
      studies confirm the up-regulation of c-jun, jun-B, c-fos and cyclin D1 by H.
      pylori. We report for the first time the induction of the serine threonine kinase
      pim-1 and ATF3 by H. pylori infection of AGS cells. CONCLUSIONS: In this
      microarray analysis of gene expression induced by H. pylori in gastric epithelial
      cells, we identified a large number of unsuspected genes affected by H. pylori.
      Further, we show that unsupervised hierarchical cluster analysis can provide
      useful insight into the possible contribution of genes in specific pathways,
      based on their profile of expression.

PMID- 11966536
TI  - No difference in the level of gastric mucosal cell apoptosis and proliferation in
      Helicobacter pylori-colonized p53 heterozygous knockout mice.
AB  - BACKGROUND: We previously reported that attenuated epithelial apoptosis and
      enhanced proliferation in comparison with mice might link to the specific
      carcinogenesis in Mongolian gerbils and suggested that the difference in both
      strains might be due to a difference in genetic background. p53 is a well-known
      tumour suppressor gene, mutation of which is also known to be involved in gastric
      cancer formation. AIM: The present study was designed to examine the level of
      gastric epithelial apoptosis and proliferation in p53 heterozygous knockout mice
      (p53+/-) colonized with Helicobacter pylori (Sydney strain: SS1). METHODS: Female
      p53+/- mice and wild-type controls were orally inoculated with SS1 and the
      stomachs were examined 24 weeks later. DNA fragmentation was measured by levels
      of cytoplasmic mono- & oligo-nucleosomes as well as by the TUNEL method. Gastric
      mucosal proliferative activity was morphometrically evaluated from the PCNA
      stained tissue specimens. Gastric mucosal myeloperoxidase (MPO) activity was
      measured to evaluate mucosal inflammation. RESULTS: DNA fragmentation and the
      number of TUNEL-positive cells, as well as PCNA-positive cell number increased
      significantly in both groups of H. pylori-infected mice, suggesting that levels
      of apoptosis and proliferation may be independent of a deficiency of one p53
      allele. MPO activity in p53+/- mice and wild-type controls increased to the same
      level. CONCLUSION: Although H. pylori inoculation per se induces an increase in
      cell turnover in mice, heterozygous mutation of p53 did not significantly modify
      the balance in cell apoptosis and proliferation.

PMID- 11966537
TI  - High molecular protein of Helicobacter pylori responsible for inhibition of
      ornithine decarboxylase activity of human gastric cultured cells.
AB  - BACKGROUND: Ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine
      biosynthesis, mediates epithelial cell proliferation and plays a critical role in
      the optimal repair of gastric mucosal damage. Several studies have shown that
      Helicobacter pylori inhibits the growth and proliferation of gastric cells in
      vitro. AIM: To test whether H. pylori extract affects ODC mRNA expression and its
      enzyme activity in gastric cells and to examine the partial characterization of
      the molecule responsible for this effect. METHODS: Human gastric cells (MKN-45)
      were used. Bacterial extracts from various E. coli or H. pylori strains, namely
      (1) cagA+, vacA+, CagA+, VacA+; (2) cagA+, vacA+, CagA+ VacA-; or (3) cagA-,
      vacA+, CagA-, VacA- were added to the cells. Cell proliferation was assessed by
      [3H]-thymidine incorporation, viability by MTT assay and LDH release test, ODC
      enzyme activity by 14CO2 counts from L-[1(14)C]ornithine, and ODC mRNA by
      Northern blotting. RESULTS: H. pylori and E. coli extract did not affect
      viability of gastric cells. H. pylori extract, especially extracts containing a
      protein greater than 50 kDa, significantly inhibited proliferation and ODC
      activity of gastric cells while E. coli extract had no effect. Inhibition of ODC
      activity was found in extracts of all H. pylori strains, irrespective of CagA and
      VacA protein expression. Serum stimulation induces an increase in ODC mRNA while
      H. pylori extract did not affect ODC mRNA expression. CONCLUSION: High molecular
      weight (greater than 50 kDa) proteins of H. pylori extract without CagA or VacA
      protein inhibited proliferation and ODC activity of human gastric cells, but did
      not affect ODC mRNA expression, suggesting that inhibition of ODC activity is
      regulated at the post-transcriptional level.

PMID- 11966538
TI  - Persistent increase in myofibroblasts in Helicobacter heilmannii-infected mice
      but not in Helicobacter pylori-infected Mongolian gerbils: colocalization of COX
      2 and bFGF immunoreactivity.
AB  - BACKGROUND: The clinical significance of Helicobacter heilmannii infection
      remains uncertain, owing to the lack of a specific detection method. Recently, we
      reported a marked increase in myofibroblasts in the early stage of Helicobacter
      pylori infection in Monglian gerbils. AIM: The present study was designed to
      clarify changes in myofibroblasts, and in the immunoeactivities of basic
      fibroblast growth factor, cyclooxygenase-2 and inducible nitric oxide synthase
      after H. pylori infection in Monglian gerbils and H. heilmannii infection in
      mice. METHODS: After oral inoculation, changes in the location of bacteria and
      the immunoreactivity of myofibroblasts, basic fibroblast growth factor,
      cyclooxygenase-2 and inducible nitric oxide synthase were stained with the
      indirect immunofluorescent method and observed by confocal laser microscopy.
      RESULTS: In H. heilmannii-infected mice, the increases in myofibroblasts and in
      immunoreactivities of these three markers were sustained 12 months after
      infection. In H. pylori-infected Monglian gerbils, however, these increases were
      significant at 3 months but had returned to control levels at 12 months.
      CONCLUSIONS: Two types of Helicobacter infection showed different patterns of
      myofibroblast proliferation, coinciding with the extent of inflammation. These
      findings suggest that this difference may be related to the consequences of the
      infection.

PMID- 11966539
TI  - Autonomic nervous activity before and after eradication of Helicobacter pylori in
      patients with chronic duodenal ulcer.
AB  - BACKGROUND: Helicobacter pylori infection is involved in the formation of chronic
      peptic ulcer. However, a previously reported hypothesis concerning the
      involvement of central autonomic nervous disorder in this condition cannot be
      ruled out. AIM: To use spectrum analysis of heart rate viability to examine
      autonomic nervous activity before and after H. pylori eradication. METHODS:
      Twenty patients with chronic duodenal ulcer (duodenal ulcer group) and 20 age
      matched normal adults (N group). In both groups, 24-h Holter electrocardiograms
      (ECGs) were recorded and spectrum analysis of heartrate variability was
      performed. In the duodenal ulcer group, Holter ECG was recorded before and after
      H. pylori eradication. RESULTS: In the N group, analysis of heart rate
      variability showed that high frequency (HF) power, an index of parasympathetic
      activity, was high at night, while the low frequency (LF)/HF ratio, an index of
      sympathetic function, was high during the daytime. In the duodenal ulcer group,
      HF power was higher at night than during the daytime, showing a similar pattern
      to the N group, but the power value was higher than in the N group (P < 0.05). In
      the duodenal ulcer group, LF/HF at night was significantly higher than that of
      the N group. In addition, in the duodenal ulcer group, autonomic activity after
      H. pylori eradication did not differ significantly from that before H. pylori
      eradication. CONCLUSIONS: In patients with chronic peptic ulcer, both
      sympatheticotonia and parasympatheticotonia may occur at night, and this
      abnormality in autonomic nervous activity may cause increased gastric acid
      secretion and gastric mucosal vasoconstriction. Abnormalities in autonomic
      activity persist even after H. pylori eradication, suggesting that they may be an
      independent risk factor in the formation of chronic peptic ulcer in addition to
      H. pylori infection.

PMID- 11966540
TI  - Sensitivity of biopsy site in evaluating regression of gastric atrophy after
      Helicobacter pylori eradication treatment.
AB  - BACKGROUND: Helicobacter pylori infection is a major cause of the progress of
      gastric glandular atrophy, a high-risk background factor in the development of
      gastric cancer. Regression of gastric atrophy is critical to prevention of cancer
      by H. pylori eradication treatment. However, it is controversial whether gastric
      atrophy regresses after H. pylori eradication. AIM: To determine the most
      sensitive and appropriate biopsy site for evaluation of regression of atrophy
      after treatment. SUBJECTS AND METHODS: Thirty-eight patients who showed
      regression of gastric atrophy in histology after treatment were investigated.
      Four biopsy specimens from the lesser and greater curvatures in the antrum and
      corpus were evaluated before and after treatment according to the Updated Sydney
      System. RESULTS: Regression of atrophy after treatment was seen in 30 of 38
      biopsy specimens from the lesser curvature of the corpus (79%), and this site was
      most sensitive. Odds ratio of this site to the others was 8.28. Regression of
      atrophy in this site was observed at 12.2 months in the younger patients and 15.9
      months in the elder patients. CONCLUSION: Biopsy sampling from the lesser
      curvature of the corpus is the most sensitive and appropriate for evaluation of
      regression of gastric atrophy after H. pylori eradication treatment.

PMID- 11966541
TI  - Role of elastase and active oxygen species in gastric mucosal injury induced by
      aspirin administration in Helicobacter pylori-infected Mongolian gerbils.
AB  - BACKGROUND: H. pylori infection potentiates aspirin-induced gastric mucosal
      injury by mechanisms that include accumulation of activated neutrophils. AIM: To
      determine the role of elastase and active oxygen species (AOS) produced by
      activated neutrophils in the gastric mucosal injury induced by administration of
      acidified aspirin to H. pylori-infected Mongolian gerbils. METHODS: H. pylori
      ATCC43504 culture broth was administered by oral gavage to male Mongolian gerbils
      at 7 weeks of age. After 4 weeks, acidified aspirin (400 mg/kg) was administered
      orally, and 3 h later, the total area of gastric erosions, myeloperoxidase (MPO)
      activity (an index of neutrophil accumulation), thiobarbituric acid-reactive
      substances (TBARS, an index of lipid peroxidation), and KC/GRO (a chemo
      attractive cytokine in rodents) were measured in gastric mucosa. To determine the
      role of elastase or AOS derived from neutrophils in these circumstances, ONO-5046
      (an elastase inhibitor), a combination of superoxide dismutase (SOD) and catalase
      (scavengers of AOS), and polaprezinc (an anti-ulcer agent with anti-inflammatory
      effects) were administered before aspirin. RESULTS: ONO-5046 inhibited the
      increase in gastric erosions and mucosal TBARS induced by administration of
      aspirin to H. pylori-infected gerbils, but not the increases in MPO activity or
      KC/GRO contents. A combination of SOD and catalase or polaprezinc significantly
      reduced gastric erosions, TBARS concentrations, MPO activity and KC/GRO
      concentration. CONCLUSIONS: These results suggest that neutrophil-derived
      elastase and -oxidants play an important role in the gastric mucosal injury
      induced by administration of aspirin to H. pylori-infected gerbils.

PMID- 11966542
TI  - Ten-year prospective follow-up study on the relationship between Helicobacter
      pylori infection and progression of atrophic gastritis, particularly assessed by
      endoscopic findings.
AB  - AIM: To ascertain the progression of atrophic gastritis due to Helicobacter
      pylori infection, we conducted a 10-year prospective follow-up study with annual
      endoscopy of the stomach. METHODS: Prospective endoscopic observation was started
      in 53 subjects in 1989 and 1990 after informed consent was obtained. The
      progression of atrophic gastritis was evaluated mainly by the endoscopic pattern
      of atrophy. Histological assessment was performed on biopsy specimens taken from
      the lesser curvature of the lower corpus. By 2000, 43 patients (20 males, 23
      females, mean age 56.7 years at entry) had completed at least 10 years of
      endoscopic follow-up. RESULTS: Eight H. pylori-negative patients with normal
      fundic mucosa showed no change endoscopically or histologically. In 35 H. pylori
      positive patients, the progression of histological atrophy was observed in 46%
      and intestinal metaplasia was observed in 49%. Fifteen of 35 H. pylori-positive
      cases exhibited a cephaloid shift of the endoscopic atrophic border. The
      cephaloid shift of the atrophic area occured suddenly. The cumulative progression
      rate of atrophic patterns was 6% after 2 years, 22% after 4 years, 34% after 6
      years and 43% after 10 years. These atrophic changes were related to neutrophil
      infiltration. CONCLUSION: The progression of atrophic gastritis is a result of
      chronic active gastritis caused by H. pylori infection.

PMID- 11966543
TI  - Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer
      disease.
AB  - BACKGROUND: The NIH consensus conference in 1994 recommended that all patients
      with peptic ulcers should be tested and treated for Helicobacter pylori. Recent
      studies have shown that the eradication of H. pylori is associated with a
      significant reduction in the relapse rate of peptic ulcers, but there are few
      reports about long-term outcome. AIMS: To evaluate the relapse rate of peptic
      ulcer in the long-term follow-up of patients after H. pylori eradication therapy.
      PATIENTS AND METHODS: Patients infected with H. pylori (445; 88 duodenal ulcer,
      357 gastric ulcer) were randomly divided into three groups. In group A, patients
      received 'conventional treatment' including acid decreasing therapy with a
      histamine H2-receptor antagonist or proton pump inhibitor (PPI). In group B,
      patients received 'dual therapy' including one antibiotic plus acid-decreasing
      therapy. In group C, patients received 'triple therapy' with PPI plus amoxicillin
      and clarithromycin. Eradication of H. pylori infection was assessed by histology
      of biopsy specimens from both the antrum and body corpus at 4 weeks, and 6 and 12
      months after stopping therapy. Endoscopy was performed at intervals of 6 months
      for 5 years. RESULTS: Intention-to-treat eradication rates for the duodenal ulcer
      patients were 0% for group A, 46% for group B and 80% for group C; eradication
      rates for the gastric ulcer patients were 0%, 33% and 83% respectively. No
      recurrence was noted in the duodenal ulcer patients and only 4% of gastric ulcers
      recurred after successful eradication during follow-up for 5 years. In contrast,
      in patients with persistent H. pylori infection all DU and 92% of gastric ulcers
      recurred. CONCLUSION: Eradication of H. pylori infection changes the natural
      course of peptic ulcer.

PMID- 11966544
TI  - Effect of acid suppression therapy on development of gastric erosions after cure
      of Helicobacter pylori infection.
AB  - BACKGROUND: Helicobacter pylori eradication markedly improves histological
      inflammation and decreases peptic ulcer recurrence, but little is known about the
      subsequent development of gastric mucosal injury. AIM: To investigate whether
      acid suppression treatment after eradication influences the development of
      gastric erosions. METHODS: Eighty-one patients (gastritis or peptic ulcer) after
      successful H. pylori eradication were divided into two groups: 40 received an H2
      blocker for 6 months (H2-blocker-positive) and 41 received no treatment (H2
      blocker-negative). Endoscopy was performed before, and at 3 and 6 months after
      completion of eradication. RESULTS: Cumulative prevalence of gastric erosions in
      the H2-blocker-positive group was significantly lower than in the H2-blocker
      negative group, 25% vs. 42%, respectively. In the H2-blocker-negative group but
      not the H2-blocker-positive group, the cumulative prevalence of gastric erosions
      after eradication was higher in patients with less severe corpus atrophy or more
      severe corpus gastritis. CONCLUSIONS: Development of gastric erosions after H.
      pylori eradication may be controlled by acid suppression treatment. Less severe
      atrophy or more severe gastritis in oxyntic glands before eradication may be
      involved in the development of gastric erosions. These results support the idea
      that recovery of acid secretion may be one of factors for development of gastric
      mucosal erosions after successful eradication.

PMID- 11966545
TI  - Clarithromycin increases the release of heat shock protein B from Helicobacter
      pylori.
AB  - BACKGROUND: Clarithromycin (CAM) may have certain indirect effects on
      Helicobacter pylori (H. pylori) other than its inhibitory activity on bacterial
      growth, as indicated in other infections with Gram-negative micro-organisms. In
      the present study, we examined the effects of lower concentrations of CAM on the
      release of heat shock protein B (HspB), one of the major antigenic proteins from
      H. pylori cells, as well as the changes in humoral immune response and
      histological degree of antral gastritis in patients who received eradication
      therapy with CAM. METHODS: The H. pylori strain 26695 and three CAM-resistant
      clinical isolates were cultured in broth with and without CAM (2-500 ng/mL).
      Expression of H. pylori proteins was examined by two-dimensional (2D)
      electrophoresis followed by N-terminal amino acid sequencing. Changes in host
      immune response and histological degree of antral gastritis were monitored in
      patients with peptic ulcer disease who received H. pylori eradication therapy.
      RESULTS: 2D electrophoresis showed 26 spots in extracellularly released proteins
      with different profiles from those in cytoplasmic proteins. The release of HspB
      increased after incubation with CAM (30-500 ng/mL) in all three H. pylori
      clinical isolates tested. Patients with failed H. pylori eradication after triple
      therapy with CAM, but not those with failed eradication after dual therapy
      without CAM, showed an increase in serum IgG1 and IgG2 antibodies against HspB
      along with a decrease in the degree of neutrophil and H. pylori colonization
      density in tissue sections. CONCLUSIONS: CAM may induce a humoral immune response
      against H. pylori and a decrease in gastric mucosal inflammation through up
      regulation of the release of HspB from the bacteria in infected patients.

PMID- 11966546
TI  - Proton pump inhibitor modifies inflammatory reaction in human gastric mucosa
      infected by Helicobacter pylori.
AB  - AIM: To examine whether proton pump inhibitors modify the production of oxygen
      derived free radicals and related cytokines in the human gastric mucosa infected
      with H. pylori. METHODS: Thirty-four H. pylori-positive peptic ulcer patients (23
      gastric ulcer, 11 duodenal ulcer) were enrolled. Biopsy tissue samples were
      obtained endoscopically from the antrum and corpus. Tissue content of neutrophil
      myeloperoxidase (myeloperoxidase) and IL-8 was measured by ELISA. Mucosal
      production of oxygen-derived free radical was measured using luminol-dependent
      chemiluminescence (ChL). A proton pump inhibitor (either lansoprazole 30 mg,
      omeprazole 20 mg, or rabeprazole 10 mg) was administered daily by mouth to all
      patients for 8 weeks. Endoscopic examination was then repeated, and biochemical
      analysis was performed. RESULTS: Antral myeloperoxidase decreased significantly
      after proton pump inhibitor treatment (5.23 +/- 7.00-2.76 +/- 5.11 ng/mg, P <
      0.02), but corpus myeloperoxidase was unchanged. IL-8 was also modified by proton
      pump inhibitors and these changes were parallel to those of myeloperoxidase.
      Corpus ChL was significantly increased from 88.5 +/- 69.8-159 +/- 172 counts/10
      s/mg after proton pump inhibitor treatment, whereas antrum ChL was not altered.
      H. pylori infection rate was decreased in the antrum as well as the corpus.
      CONCLUSIONS: Proton pump inhibitor treatment stimulated oxygen-derived free
      radical production in the corpus mucosa.

PMID- 11966547
TI  - Analysis of Helicobacter pylori and nonsteroidal anti-inflammatory drug-induced
      gastric epithelial injury.
AB  - BACKGROUND: Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs)
      are important factors in gastric mucosal injury. However, the relationship
      between H. pylori and NSAID-related gastroduodenal mucosal injury has not been
      clarified. AIM: To determine the role of H. pylori in NSAID-induced gastric
      mucosal injury and to examine the effects of H. pylori, indomethacin and
      sofalcone on gastric epithelial cells in culture, as a useful model to study
      gastric mucosal injury. In addition, we studied the effect of sofalcone, a
      gastric mucosal protection agent, on H. pylori and NSAID-induced gastric mucosal
      injury. METHODS: Cytotoxic and noncytotoxic strains of H. pylori were used, each
      with an inoculum of 10(7) cfu/mL. The effect on the growth of RGM-1 cells (a rat
      gastric epithelial cell line) was studied by MTT assay, and levels of
      prostaglandin E2 in culture supernatants were measured by EIA. RESULTS: Both
      cytotoxic and noncytotoxic strains of H. pylori tended to induce cell injury in
      RGM-1 cells at 48 h after inoculation. Indomethacin alone induced gastric
      epithelial injury in a dose-dependent manner, but did not augment cell injury
      induced by H. pylori. In addition, sofalcone (10(-5) mol/L) showed a suppressive
      effect on indomethacin-induced gastric epithelial injury. CONCLUSION: These
      findings indicate that indomethacin induces gastric mucosal injury regardless of
      H. pylori infection, and suggests that sofalcone may be a useful drug in the
      treatment of NSAID-induced mucosal injury.

PMID- 11966548
TI  - Eradication of Helicobacter pylori infection induces an increase in body mass
      index.
AB  - BACKGROUND: The relationship between H. pylori infection and body mass indices is
      controversial. AIM: To investigate the relationship between H. pylori infection
      and body indices, and to examine the effect of H. pylori eradication therapy on
      body indices. METHODS: Nine-hundred and thirty-two employees of an industrial
      corporation were examined for H. pylori infection and body mass indices. Three
      hundred and two H. pylori-positive cases diagnosed with chronic gastritis by
      upper gastrointestinal endoscopy or radiography underwent eradication therapy.
      Body mass indices, serum total cholesterol levels and symptom scores were
      obtained before and at 12 months after eradication therapy. RESULTS: There was no
      significant difference in body weight, body mass index (BMI) or serum total
      cholesterol level between the H. pylori-positive and H. pylori-negative groups.
      However, body weight and BMI increased significantly 12 months after eradication
      of H. pylori infection. In contrast, there was no significant difference in body
      weight and BMI 12 months after eradication therapy in the non-eradication group.
      Serum total cholesterol levels did not change after eradication therapy in either
      the eradication or non-eradication groups. CONCLUSION: Eradication of H. pylori
      infection induced an increase in BMI in industrial workers with chronic gastritis
      in Japan.

PMID- 11966549
TI  - Anaesthesia in the magnetic resonance unit: a hazardous environment.

PMID- 11966550
TI  - Efficacy of ropivacaine compared with ropivacaine plus sufentanil for
      postoperative analgesia after major knee surgery.
AB  - This study compared the analgesic efficacy of an epidural infusion of ropivacaine
      and ropivacaine with sufentanil following major knee surgery. In a double-blind
      clinical trial, 115 adult patients received either epidural ropivacaine (R group,
      2 mg.ml(-1)), or ropivacaine (2 mg.ml(-1)) with sufentanil (RS group, 1
      microg.ml(-1)), using a patient-controlled epidural analgesia technique. Pain
      scores (visual analogue scale, VAS, and the simple descriptive scale, SDS), side
      effects, motor block and treatment quality were recorded at 6, 12 and 24 h after
      the insertion of the epidural catheter. In the RS group, analgesic efficacy was
      significantly greater than in the R group between 12 and 24 h following insertion
      of the epidural catheter (VAS: 92.9% vs. 72.9%, p = 0.009). There was no
      significant difference during the other periods. Pruritus, nausea and vomiting
      were significantly more frequent in the RS group. Good postoperative analgesia
      was obtained with an epidural infusion of ropivacaine (2 mg.ml(-1)). When this
      local anaesthetic was administered with sufentanil, there was an improvement in
      the analgesic effect but a significant increase in the number of patients who
      reported adverse effects. The differences were more pronounced 12 h after the
      beginning of the analgesic schedule. This study failed to demonstrate any
      worthwhile clinical benefit from the addition of sufentanil.

PMID- 11966551
TI  - Study of a combined percutaneous local anaesthetic and nitric oxide-generating
      system for venepuncture.
AB  - Nitric oxide (NO) may be generated and delivered into the skin via a novel system
      of sodium nitrite and ascorbic acid. This placebo-controlled, double-blind trial
      compared the analgesic properties of this system alone and when supplemented with
      lidocaine. The pain of dorsal hand vein cannulation was assessed in 100
      volunteers. The NO-generating system was prepared by mixing two gels, the first
      KY jelly and sodium nitrite (10% w/v), the second KY jelly and ascorbic acid (10%
      w/v). NO-generating gel was the placebo treatment, and when combined with
      lidocaine (final concentration 5%), formed the active treatment. The gels were
      applied to the dorsum of the hands bilaterally and simultaneously for 10 min.
      Following cannulation, pain perception was measured with a verbal rating score
      (VRS) and a visual analogue score (VAS). The active formulation significantly
      decreased the VRS (p < 0.0001) and also reduced the mean VAS by > 40% compared
      with placebo (p < 0.001). This investigation suggests a 10-min topical
      application of anaesthetic combined with the NO-generation system may provide
      effective analgesia for venous cannulation in adults.

PMID- 11966552
TI  - Outcome evaluation in a surgical intensive care unit in Barbados.
AB  - The performance of the Acute Physiology and Chronic Health Evaluation II scoring
      system was prospectively assessed in the surgical intensive care unit at the
      Queen Elizabeth Hospital, Barbados. A total of 309 patients admitted
      consecutively during a 2-year period (1999-2001) were evaluated. Demographic
      data, diagnosis, Acute Physiology and Chronic Health Evaluation II score,
      duration of stay and hospital outcome were recorded. The predicted mortality for
      every patient and the costs incurred were also calculated. The overall observed
      mortality rate was 15.9% while the mean predicted mortality rate for our case-mix
      was 16.4%, which is comparable to results from developed countries. The cost
      incurred per patient was much lower at $13,636 (Barbados), compared to the
      patients' cost in North America ($60,000 Barbados).

PMID- 11966553
TI  - Assessment of photoplethysmographic signals for the determination of splanchnic
      oxygen saturation in humans.
AB  - The need for a clinically applicable method of detecting splanchnic hypoxia has
      led to experimental animal studies which indicated the usefulness of intestinal
      pulse oximetry. Pulse oximetry relies on detection of photoplethysmographic
      signals. Before developing a pulse oximeter for the measurement of organ oxygen
      saturation peri-operatively, we designed a system based on a reflectance
      photoplethysmographic probe to investigate photoplethysmographic signals from
      human viscera (bowel, liver, and kidney). Recordings were obtained simultaneously
      from the abdominal viscera and the finger using identical probes. The probe was
      held sequentially for up to 2 min on the surface of viscera of 12 patients during
      routine laparotomy. Measurable splanchnic photoplethysmographic signals were
      recorded for the first time in humans. There were no statistically significant
      differences between photoplethysmographic amplitudes from viscera and those from
      the finger. Our results indicate the feasibility of pulse oximetry for the
      measurement of visceral oxygenation in humans.

PMID- 11966554
TI  - Comparison of sevoflurane and nitrous oxide mixture with nitrous oxide alone for
      inhalation conscious sedation in children having dental treatment: a randomised
      controlled trial.
AB  - We studied 411 children aged 3-10 years who were referred for dental treatment.
      They were randomly allocated to have inhalation conscious sedation with either
      sevoflurane/nitrous oxide mixture or nitrous oxide alone. Dental treatment was
      satisfactorily completed in 215/241 children who were given sevoflurane/nitrous
      oxide mixture (89%) compared with 89/170 who were given nitrous oxide alone (52%)
      (Chi square 70.3, p < 0.0001). All children remained conscious and responsive to
      verbal contact throughout the treatment and in the recovery room. No adverse side
      effects were recorded in either group and there were no significant differences
      in oxygen saturation, heart rate, recovery profile, or time to discharge home
      between the groups. The study concluded that, for every 100 children treated with
      sevoflurane/nitrous oxide mixture, 37 children would be saved a general
      anaesthetic if given combined sevoflurane and nitrous oxide mixture rather than
      nitrous oxide alone. The use of sevoflurane in low concentrations 0.1-0.3% to
      supplement nitrous oxide and oxygen for inhalation conscious sedation is safe,
      practical, and significantly more effective than nitrous oxide alone in children
      having dental treatment.

PMID- 11966555
TI  - Gabapentin: pharmacology and its use in pain management.
AB  - Although its exact mode of action is not known, gabapentin appears to have a
      unique effect on voltage-dependent calcium ion channels at the postsynaptic
      dorsal horns and may, therefore, interrupt the series of events that possibly
      leads to the experience of a neuropathic pain sensation. Gabapentin is especially
      effective at relieving allodynia and hyperalgesia in animal models. It has been
      shown to be efficacious in numerous small clinical studies and case reports in a
      wide variety of pain syndromes. Gabapentin has been clearly demonstrated to be
      effective for the treatment of neuropathic pain in diabetic neuropathy and
      postherpetic neuralgia. This evidence, combined with its favourable side-effect
      profile in various patient groups (including the elderly) and lack of drug
      interactions, makes it an attractive agent. Therefore, gabapentin should be
      considered an important drug in the management of neuropathic pain syndromes.

PMID- 11966556
TI  - Morton's design of the early ether vaporisers.
AB  - The exact design of the ether vaporiser used by William Morton on 16 October 1846
      has remained uncertain with many contradictory reports. This article explores the
      known facts and speculates on the design used on that and subsequent occasions.

PMID- 11966557
TI  - Assessment of the Caradyne WhisperFlow for administration of continuous positive
      airway pressure in a 3 Tesla magnetic resonance scanner.
AB  - Demand for magnetic resonance investigations in critically ill patients is
      increasing. While these patients frequently need ventilatory support, not all of
      them require controlled ventilation and many may be treated with continuous
      positive airway pressure. Controlled ventilation, with the concurrent need for
      sedation, may be inappropriate when airway physiology is being studied and may
      retard weaning. No commercially available ventilator designed for the magnetic
      resonance environment can deliver high flow continuous positive airway pressure.
      We tested the Caradyne Whisperflow flow generator and five Whisperflow valves
      (2.5-15 cmH2O airway pressure) within a 3 Tesla environment for safety and
      possible dysfunction. All components had minimal ferromagnetic properties and
      tests showed no clinically relevant change in flow delivery or oxygen
      concentration in the magnetic field. In addition, the airway pressure generated
      by the valves was not affected by the magnetic field. We conclude that the tested
      system can be safely used in a 3 Tesla magnetic resonance environment.

PMID- 11966558
TI  - Nasopharyngeal airway continuous positive airway pressure: a method to wean from
      or avoid mechanical ventilation in adults.
AB  - A simple technique using a nasopharyngeal airway and a continuous positive airway
      pressure circuit has proved an effective alternative to a tight fitting nasal or
      face mask for delivery of continuous positive airway pressure. Nasal trauma,
      discomfort and mouth breathing are the main disadvantages.

PMID- 11966559
TI  - Severe hyperphosphataemia and associated electrolyte and metabolic derangement
      following the administration of sodium phosphate for bowel preparation.
AB  - Sodium phosphate is widely used as an effective bowel preparation agent. It is
      used in smaller volumes, leading to improved patient tolerance. Although it is
      generally safe, cases of severe hyperphosphataemia following sodium phosphate
      administration have been reported in the literature. The common risk factors
      identified are advanced age, impaired renal function, impaired colonic motility
      and multiple doses. However, many doctors remain unaware of the dangers
      associated with this agent. We report six cases of severe electrolyte and
      metabolic derangement due to sodium phosphate bowel preparation: two patients had
      delayed awakening from general anaesthesia, and four patients suffered life
      threatening consequences.

PMID- 11966560
TI  - Anaesthesia and the elderly.

PMID- 11966561
TI  - An alternative suctioning technique.

PMID- 11966562
TI  - Is your bougie helping or hindering you?

PMID- 11966563
TI  - Posterior tracheal wall tear with PercuTwist.

PMID- 11966564
TI  - Christmas 'trachys'.

PMID- 11966565
TI  - Pre-oxygenation.

PMID- 11966567
TI  - Monitoring of the anaesthetic volatile agent may be impaired in hydrocarbons
      abusers.

PMID- 11966568
TI  - Anaesthetic management of a patient with Stiff-person syndrome.

PMID- 11966569
TI  - Paravertebral block.

PMID- 11966570
TI  - The 'facial flashing' of aortic regurgitation.

PMID- 11966571
TI  - Male antisperm antibodies: association with a modified sperm stress test and
      lipid peroxidation.
AB  - We previously reported a modified sperm stress test (MOST), low scores (< 0.39)
      in which were associated with sperm-related abnormal in vitro fertilization.
      Preliminary observations suggested that the presence of male sperm antibodies
      (ASA) could give low MOST scores. It was therefore decided to undertake a study
      to verify this possible association and also to ascertain if such a relationship
      was causal in nature. Six hundred and fifty semen samples from patients
      consulting for infertility were assessed for basic seminal characteristics,
      motion parameters (CASA), ASA and MOST. Thirty-nine samples (6%) were ASA
      positive. Samples with and without ASA showed similar characteristics, except for
      percentage of normal forms and MOST scores (0.35 +/- 0.03 vs. 0.67 +/- 0.01, P <
      0.001, for ASA-positive and -negative, respectively). There was a strong
      statistical association between presence of ASA and low MOST scores (P < 0.0001).
      One-hundred per cent of ASA-positive samples displayed low MOST scores. To verify
      the nature of this relationship, we incubated ASA-free spermatozoa with ASA
      positive and -negative (control) sera. Despite an increase in the percentage of
      ASA-bearing spermatozoa in those aliquots incubated with ASA-positive serum,
      their original (pre-incubation) MOST scores remained unchanged. Furthermore, the
      rate of lipid peroxidation, indirectly reflected in MOST scores, was not
      different in the aliquots incubated with ASA. In conclusion, there seems to be a
      strong association between presence of ASA and low MOST values in semen samples
      of infertile patients; however, the relationship does not appear to be causal.

PMID- 11966572
TI  - Indirect immunofluorescence using monoclonal antibodies for the detection of
      leukocytospermia: comparison with peroxidase staining.
AB  - The presence of increased number of leukocytes in semen is indicative of
      inflammation in the male genital tract. Inflammatory processes at this level may
      lead to marked impairment of sperm function, and finally to a reduction in their
      fertilizing capability. An immunocytological technique for the detection of
      seminal leukocytes was evaluated in this study. As part of the standardization
      technique, different fixation methods were tested to ascertain whether samples
      could be stored and examined later. It was found that fixation with cold acetone
      at freezing temperatures retained immunoreactivity until day 11 of storage. All
      other methods showed a significant loss of immunoreactivity, from as little as
      day 2 of storage. In 46 specimens with elevated numbers of round cells, number of
      peroxidase-positive cells and number and type of leukocytes were evaluated by
      means of indirect immunofluorescence. Determination of peroxidase-positive cells
      to detect leukocytospermia, the standard procedure recommended by the WHO, was
      compared with the indirect immunofluorescence technique using monoclonal
      antibodies. While 19 of 46 patients showed high numbers of leukocytes in the
      ejaculate, as determined by the immunocytological method, only 9 of these were
      identified to be leukocytospermic, according to the WHO (standard) procedure.
      This difference was statistically significant (P < 0.01) and indicates that the
      standard method of detection of seminal leukocytes may be inaccurate.

PMID- 11966573
TI  - Reactivation of motility of demembranated hamster spermatozoa: role of protein
      tyrosine kinase and protein phosphatases.
AB  - Demembranated cauda epididymidal spermatozoa of hamster, following reactivation
      with 1 mm ATP, exhibited either a loop or planar type of motility. The
      spermatozoa with planar motility exhibited increased progressive velocity (VSL),
      straightness (STR), linearity (LIN) and beat cross frequency (BCF) compared to
      the spermatozoa with loop type motility. cAMP was observed to have differential
      effects on the motility parameters of the demembranated spermatozoa depending on
      the type of motility. For instance, in the loop type, average path velocity
      (VAP), curvilinear velocity (VCL) and VSL were increased in the presence of cAMP
      unlike in the planar type. Furthermore, in an attempt to understand the role of
      protein kinases and protein phosphatases in regulation of sperm motility, the
      effects of various inhibitors of these enzymes on the motility and
      phosphorylation of proteins of reactivated demembranated spermatozoa were
      studied. Inhibitors of PTKase (protein tyrosine kinase) and protein phosphatases
      inhibited the motility of reactivated demembranated hamster spermatozoa. The
      activity of the respective enzymes associated with demembranated spermatozoa was
      concurrently inhibited, thus providing evidence that the effect of the inhibitors
      on motility was mediated through their inhibitory effects on the activities of
      the enzymes. The results also demonstrated that two phosphotyrosinylated proteins
      of molecular weight 65 and 80 kDa showed reduced phosphorylation in the presence
      of PTKase inhibitors, thus indicating their possible role in reactivation of
      motility of demembranated hamster spermatozoa.

PMID- 11966574
TI  - Are viral infections the cause of leukocytospermia?
AB  - Leukocytospermia is defined as a leukocyte count of more than 1 x 106 ml-1
      ejaculate. It may be a symptom of male accessory gland infection, but is also
      observed in up to 10% of asymptomatic patients presenting for infertility work
      up. Pathogenic bacteria are not present in all of these semen samples. We
      attempted to find evidence for infection with cytomegalovirus, Epstein-Barr virus
      and herpes simplex virus by determining antibodies in serum in 130 patients with,
      and 80 patients without, leukocytospermia and by polymerase chain reaction in 50
      further patients and controls. All semen samples with or without leukocytospermia
      were free from clinically significant concentrations of pathogenic bacteria. Only
      IgM antibodies against HSV were found more frequently in patients with
      leukocytospermia than in the controls (10.8 and 1.25%, respectively). All other
      virus antibody findings showed an equal frequency in both groups. The
      determination of HSV DNA in 50 further semen samples with, and 50 samples
      without, leukocytospermia revealed no positive results. Although our study
      indicates an association of herpes virus infection and leukocytospermia in 10% of
      cases, the mechanism of association is to be clarified.

PMID- 11966575
TI  - Lactate dehydrogenase-C4 is involved in heparin- and NADH-dependent bovine sperm
      capacitation.
AB  - Lactate dehydrogenase C4 isoenzyme (LDH-C4) is involved in the energy metabolism
      of spermatozoa. Sperm capacitation is considered part of an oxidative process; an
      NADH oxidase of plasma membrane could be responsible for superoxide anion
      generation which is required for capacitation. The role of LDH-C4 and the
      requirements of NADH in cryopreserved bovine sperm capacitation were studied. LDH
      C4 activity was 5.52 +/- 3.41, 15.72 +/- 6.04 and 15.22 +/- 1.92 Units 1010
      spermatozoa-1 in plasma membrane, sperm suspension and cytosol fraction,
      respectively; these activities were inhibited by sodium oxamate. To study the
      influence of oxidative substrates in capacitation, three different TALP (T) media
      were used: TP (pyruvate); TL (lactate) and TC (citrate); heparin or NADH was then
      added. There were no significant differences in the percentage of capacitation
      induced by heparin or NADH in TALP medium; similar levels of capacitation were
      achieved with TL alone or TL +heparin and TP +NADH; capacitation was inhibited
      with sodium oxamate in all treatments used. Cytosolic NADH may be required as a
      substrate for sperm oxidase. Lactate influx through plasma membrane may be
      utilized by cytosolic LDH-C4, increasing reduced coenzymes required for
      capacitation. Plasma membrane LDH-C4 may participate in the production of lactate
      to obtain intracellular reducing equivalents to be used by sperm oxidase for in
      vitro sperm capacitation.

PMID- 11966576
TI  - The role of expression of extracellular matrix proteins and epidermal growth
      factor receptor activity on fertilization capacity of testicular harvested
      spermatozoa.
AB  - It has been suggested that multiple growth factors are crucial for
      spermatogenesis. We analyzed whether alterations on epidermal growth factor
      receptor activity and different expression pattern of extracellular matrix
      proteins had an impact on the fertilization capacity of spermatozoa and pregnancy
      rate after testicular sperm extraction and intracytoplasmic injection.
      Extracellular matrix proteins and epidermal growth factor receptor were
      immunohistochemically evaluated in testis of 88 patients with nonobstructive
      azoospermia. Testicular sperm extraction and intracytoplasmic injection procedure
      was also performed in 32 of the patients for whom mature sperm could be harvested
      from the testicular tissue. While collagen Type-IV and laminin activity
      percentages were 33.1% and 86.4% in motile sperm harvested testicular tissue,
      these activities were 23.3% and 89.3% in immotile sperm harvested testicular
      tissue, respectively. In addition, the mean epidermal growth factor receptor
      expression was higher in immotile than motile sperm obtained tissue (56.4% vs.
      51.1%, P=0.4928). There was no statistically significant relationship between the
      extracellular matrix protein and epidermal growth factor receptor expression
      patterns and sperm motility, fertilization and pregnancy rates in testicular
      sperm extraction and intracytoplasmic injection. However, further studies are
      required to investigate the relationship between other growth factors and sperm
      fertilization capacity.

PMID- 11966577
TI  - Coenzyme Q10 levels in idiopathic and varicocele-associated asthenozoospermia.
AB  - Levels of coenzyme Q10 (CoQ10) and of its reduced and oxidized forms (ubiquinol,
      QH2, and ubiquinone, Qox) have been determined in sperm cells and seminal plasma
      of idiopathic (IDA) and varicocele-associated (VARA) asthenozoospermic patients
      and of controls. The results have shown significantly lower levels of coenzyme
      Q10 and of its reduced form, QH2, in semen samples from patients with
      asthenospermia; furthermore, the coenzyme Q10 content was mainly associated with
      spermatozoa. Interestingly, sperm cells from IDA patients exhibited significantly
      lower levels of CoQ10 and QH2 when compared to VARA ones. The QH2/Qox ratio was
      significantly lower in sperm cells from IDA patients and in seminal plasma from
      IDA and VARA patients when compared with the control group. The present data
      suggest that the QH2/Qox ratio may be an index of oxidative stress and its
      reduction, a risk factor for semen quality. Therefore, the present data could
      suggest that sperm cells, characterized by low motility and abnormal morphology,
      have low levels of coenzyme Q10. As a consequence, they could be less capable in
      dealing with oxidative stress which could lead to a reduced QH2/Qox ratio.
      Furthermore, the significantly lower levels of CoQ10 and QH2 levels in sperm
      cells from IDA patients, when compared to VARA ones, enable us to hypothesize a
      pathogenetic role of antioxidant impairment, at least as a cofactor, in
      idiopathic forms of asthenozoospermia.

PMID- 11966578
TI  - Pro-inflammatory cytokine response of the fluid contents of spermatoceles and
      epididymal cysts.
AB  - The aim of the study was to determine the cellular contents and concentrations of
      interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF
      alpha) in fluids of patients with spermatocele or epididymal cyst. Twenty-five
      symptomatic patients, 14 with epididymal cysts and 11 with spermatoceles, were
      included in the study. Fluids were obtained during surgical excision of the cysts
      and cytological smears were stained with May-Gruenwald-Giemsa to establish cell
      components. The concentrations of IL-6, IL-8 and TNF-alpha were measured by
      chemiluminescent immunometric assay. Cytological analysis of the fluids
      demonstrated various sperm forms ranging from immature germ cells to degenerated
      spermatozoa without inflammatory cells such as neutrophils and macrophages. The
      concentrations (mean+/- SEM, pg/mg protein) of IL-6, IL-8 and TNF-alpha were
      13.52 +/- 1.40, 22.20 +/- 2.43, 3.51 +/- 1.43 in spermatocele fluids and 5.76 +/-
      0.48, 11.57 +/- 1.89, 2.53 +/- 0.41 in epididymal cyst fluids. Both IL-6 and IL-8
      concentrations in the spermatocele group were higher than in the epididymal cyst
      group (P < 0.0001). There were no differences in TNF-alpha concentrations between
      the groups (P > 0.05). These findings indicate that local production of pro
      inflammatory cytokines is involved in cyst formation. The presence of immunologic
      activation in these fluids advocates a policy of selective surgical intervention
      in patients with spermatocele or epididymal cyst.

PMID- 11966579
TI  - Comparison of semen quality in older and younger men attending an andrology
      clinic.
AB  - The effects of age on semen quality were analysed in patients referred to an
      andrology outpatient clinic in a retrospective study covering a period of 3
      years. Semen analyses of older men (n = 66; > or = 50 years; median: 53) were
      compared with those of young patients (n = 134; 21-25 years; median 24). The
      duration of sexual abstinence was longer among older patients (median: 5.5 vs.
      5.0 days; + 10%, P < 0.05). Even after adjustment for duration of sexual
      abstinence, progressive motility (- 27%, P < 0.01), percentage of morphologically
      normal spermatozoa (- 44%, P < 0.01) and semen volume (- 29%, P < 0.0005) were
      significantly lower in older than in younger men. Impaired sperm morphology was
      mainly attributed to abnormal staining of flagella (+ 50%, P < 0.05) and an
      increased portion of coiled or bent tails (+ 44%, P = 0.001) indicating
      epididymal dysfunction. Total sperm count and sperm concentration were unaffected
      by age. Age-dependent changes in accessory gland function, as indicated by
      fructose concentration (- 27%, P < 0.05), was correlated with lower semen volume.
      Moreover, serum testosterone levels were significantly reduced in the group of
      older men (median: 3.0 vs. 3.6 ng ml-1; -17%, P < 0.005).

PMID- 11966581
TI  - Computed tomography colonography (virtual colonoscopy): review.
AB  - Computed tomography examination of the colon performed after bowel cleansing and
      distension of the lumen with gas goes by several different names--CT colonography
      (CTC) and CT colography perhaps being the most common. Strictly, the term
      'virtual colonoscopy' (VC), should be reserved for the process of examining 3-D,
      simulated endoluminal images with a capability to navigate through the bowel
      using appropriate software. Computed tomography colonography appears to be the
      name that has gained favour among radiologists, although it is suspected that
      'virtual colonoscopy' will persist as a generic term due to its attractive 'high
      tech' connotations for non-radiological medical and lay persons. Whatever the
      name, the technique has been made possible through the advent of fast helical CT
      scanners which allow acquisition of a volume of data, and of proprietary software
      which enables multiplanar reformatting and 3-D endoluminal reconstructions. It is
      evident that if CTC/VC can be shown to be acceptable to patients, safe,
      affordable and accurate, it has enormous potential as a diagnostic and screening
      tool for colorectal neoplasia.

PMID- 11966582
TI  - Soft tissue uptake on 99mTc methylene diphosphonate bone scan imaging: pictorial
      review.
AB  - 99mTechnetium methylene diphosphonate (MDP) bone isotope may accumulate in many
      extra-osseous sites due to a variety of both benign and malignant conditions.
      This finding on a bone scan can be crucial to the diagnosis and may not be
      apparent in other imaging or the clinical evaluation of the patient. We present a
      pictorial review sampling some of the many causes of extra-osseous 99mTc MDP
      accumulation.

PMID- 11966583
TI  - Ultrafast MRI of the fetus.
AB  - During the last decade there has been increasing interest in MRI for the
      evaluation of ultrasound-detected fetal abnormalities. Motion artefacts
      previously precluded detailed imaging, but this is now possible using single-shot
      rapid acquisition sequences. These ultrafast techniques with subsecond images
      capture 'snap-shot' views of the fetus. By virtue of the infinitely long
      relaxation time (TR) these images are heavily T2-weighted so that fluid around
      and within the fetus delineates the anatomy. Currently, fetal MRI has shown to be
      most beneficial in the investigation of cerebral abnormalities suspected from
      sonography, and in the detection of subtle associated anomalies. It clearly has a
      role in the evaluation of complex somatic abnormalities, and is helpful in the
      evaluation of fetuses prior to surgery. We present a pictorial review of our
      experience with single-shot fast spin-echo (SSFSE) imaging, demonstrating normal
      anatomy of the fetal brain and body. In addition we present cerebral and somatic
      abnormalities to illustrate cases where we have found fetal MRI to be a useful
      adjunct to sonography.

PMID- 11966584
TI  - MRI appearances of the sphenoid sinus at the late follow-up of trans-sphenoidal
      surgery for pituitary macroadenoma.
AB  - We aimed to demonstrate the appearances of the sphenoid sinus on MRI performed
      later than 2 years post- transsphenoidal surgery (TSS). We retrospectively
      reviewed 47 patients in whom follow-up MRI scans had been performed at least 2
      years post-TSS. We specifically reviewed the clinical and imaging of those
      patients in whom the sphenoid sinus was filled with signal abnormality or masses
      were present arising from the sinus roof and classified them as tumour or
      indeterminate abnormalities on imaging criteria. We documented other
      clinicoradiological details. Twelve of 47 patients demonstrated sphenoid sinus
      filling or sinus roof masses and in six of 12 patients it was possible to
      classify them as tumourous using imaging and clinical criteria. The indeterminate
      and non-tumourous sphenoid sinus abnormalities most frequently had a T1-weighted
      signal similar to subsellar tumour and displayed rim enhancement and thus could
      not be reliably distinguished from tumourous abnormality on the basis of signal
      or enhancement characteristics. The presence of a well-defined surgical defect in
      the sella floor was associated with resolution of abnormality on MRI follow-up.
      We concluded MRI findings of sphenoid sinus filling or sinus roof masses are
      present in approximately 26% of scans performed longer than 2 years post-TSS.
      Half of these are of indeterminate origin and follow-up is required to
      discriminate tumour from non- tumour with certainty. A well-defined surgical
      defect in the sella floor is, however, suggestive of a non-tumourous abnormality.

PMID- 11966585
TI  - Diagnosis of choledocholithiasis and bile duct stenosis by magnetic resonance
      cholangiogram.
AB  - We evaluated the diagnostic accuracy of magnetic resonance cholangiography (MRC)
      in the diagnosis of bile duct calculi and stenosis. Two-dimensional fast spin
      echo (FSE) MR cholangiograms were performed using torso multicoil array as a
      surface coil and respiratory triggering in 50 patients suspected of having bile
      duct disease. Coronal and axial images were acquired and reviewed prospectively
      by two radiologists. Direct cholangiographic correlation (endoscopic retrograde
      cholangiopancreatography [ERCP], intraoperative cholangiogram, percutaneous
      transhepatic cholangiogram) and surgery were available for comparison and were
      reviewed by two radiologists. The sensitivity, specificity and accuracy of MRC in
      diagnosing bile duct dilatation, choledocholithiasis and stenosis were evaluated.
      It yielded a sensitivity and a specificity of 100% in diagnosing bile duct
      dilatation. In the diagnosis of choledocholithiasis, MRC yielded a sensitivity of
      95%, a specificity and an accuracy of 96%. Bile duct stenosis was diagnosed with
      a sensitivity and a specificity of 100%. We concluded that MRC exhibited high
      accuracy in diagnosing bile duct stenosis and choledocholithiasis.

PMID- 11966586
TI  - Comparison of lung scintigraphy and CT angiography in the diagnosis of pulmonary
      embolism.
AB  - In our institution, as in others, pulmonary angiography is not used in the
      diagnosis of pulmonary embolism because of its perceived risks. We compared the
      results on lung scintigraphy and computed tomography angiography (CTA) in 116
      consecutive patients with suspected pulmonary embolism. In 14 patients with
      normal lung scans 13 (93%) were also normal with CTA. In the 73 patients with low
      probability lung scans only five (7%) demonstrated pulmonary embolism with CTA.
      In 12 patients with high probability lung scans 11 (92%) demonstrated pulmonary
      embolism on CTA. However, in the 17 patients with intermediate probability lung
      scans, 10 (58.8%) showed embolism with CTA. We conclude that wherever practicable
      lung scans should be performed in all patients due to its relatively low
      radiation burden and that CTA be performed in patients with intermediate
      probability scans due to the high incidence of pulmonary embolism. Patients with
      either a normal scan or high probability scan should be treated appropriately. In
      patients with low probability scans CTA should be performed in those with a high
      clinical suspicion of thromboembolism.

PMID- 11966587
TI  - Direct B-mode NASCET-style stenosis measurement and Doppler ultrasound as
      parameters for assessment of internal carotid artery stenosis.
AB  - Doppler ultrasound grading of internal carotid artery (ICA) stenosis using the
      two parameters of spectral analysis and internal carotid to common carotid artery
      peak systolic velocity (ICA/CCA PSV) ratio is well established. The improvements
      in B-Mode ultrasound image quality now make direct ultrasound NASCET-style
      stenosis measurement possible. We demonstrate that longitudinal B-mode imaging
      can produce accurate North American Symptomatic Carotid Endarterectomy Trial
      (NASCET) style measurements which have good correlation with angiographic images.
      Ultrasound B-mode stenosis measurement provides a third parameter which can be
      used in conjunction with the two Doppler parameters for the assessment of ICA
      stenosis. Taking the highest grade of stenosis of the three parameters produces a
      sensitivity of 100% for the detection of greater than 50% and greater than 80%
      stenosis with specificity of 66 and 90%, respectively. The performance of
      satisfactory B-mode imaging against digital subtraction angiography (DSA) was
      very encouraging. When the B-mode stenosis measurement showed a normal ICA, the
      positive predictive value (PPV) of the DSA being normal was 94%. When the B-mode
      stenosis measurement was 35% or less, the PPV of the DSA stenosis being 35% or
      less was 93%. These excellent results support the use of good quality B-Mode
      NASCET style stenosis measurement as the initial ultrasound measurement, with
      Doppler ultrasound only being performed when the B-mode stenosis measurement is
      greater than 35% or if the B-mode image is unsatisfactory. This approach would
      save considerable time enabling better utilization of ultrasound resources.

PMID- 11966588
TI  - Primary renal candidiasis: fungal mycetomas in the kidney.
AB  - Fungal infections of the urinary tract have a predilection for drainage
      structures rather than for the renal parenchyma. Of the causal factors, diabetes
      mellitus, immunosupressed states, AIDS and prematurity are those most commonly
      encountered. The case of a young, diabetic man whose chief clinical presentation
      was dysuria is described. On further examination he was found to harbour fungal
      balls in the right kidney. Radiological manifestations of acute pyelonephritis
      were also present. Although primary renal candidiasis is often commensurate with
      systemic fungaemia, he displayed none of the clinical features of disseminate
      infection and, hence, was treated conservatively with oral antifungal agents.
      Fortuitously, spontaneous passage of fungal particulate matter in urine was later
      reported.

PMID- 11966589
TI  - A case of primary cerebral neuroblastoma in adolescence.
AB  - Primary cerebral neuroblastoma is one of a group of highly malignant
      undifferentiated primitive neuroectodermal tumours arising from germinal matrix
      cells of the embryonic neural tube. They occur primarily in young children and
      are extremely rare in adults. They may be multicentric and have often spread
      throughout the central nervous system at the time of diagnosis. A case of a 16
      year-old man is described, and the recent literature is reviewed.

PMID- 11966590
TI  - Solitary pulmonary metastasis from intracranial meningiothelial meningioma.
AB  - Although known, histologically proven pulmonary metastasis from a benign
      intracranial meningioma is exceedingly rare. We report a case of meningiothelial
      meningioma producing a solitary pulmonary deposit.

PMID- 11966591
TI  - Renal parenchymal malakoplakia: an unusual cause of unilateral, diffuse renal
      enlargement.
AB  - Renal parenchymal malakoplakia is usually described as a multi- or unifocal
      process. We report an unusual case presenting with unilateral diffuse renal
      enlargement consistent with an early stage in the evolution of this disease.

PMID- 11966592
TI  - False negative biliary scintigraphy in gangrenous cholecystitis.
AB  - Gangrenous cholecystitis is a serious complication of acute cholecystitis and is
      associated with increased morbidity and mortality rates. We report a case in
      which the diagnosis was suggested by ultrasound, but cholecystectomy delayed due
      to atypical clinical presentation and a false negative radionuclide biliary scan.

PMID- 11966593
TI  - Cerebrospinal fluid pseudocyst of the breast.
AB  - Cerebrospinal fluid pseudocyst of the breast is a rare complication of
      ventriculoperitoneal shunt placement. Two cases of cerebrospinal pseudocyst of
      the breast are reported here. The mammography and ultrasound findings in these
      two cases are described.

PMID- 11966594
TI  - CT and MRI appearances of methotrexate leucoencephalopathy.
AB  - Methotrexate is a well recognised cause of diffuse symmetrical
      leucoencephalopathy. The widespread use of the drug in chemotherapeutic regimes
      necessitates awareness of this complication. A case report and a brief literature
      review is presented.

PMID- 11966595
TI  - Spinal angiolipoma: report of three cases and review of MRI features.
AB  - We report three cases of spinal angiolipoma, two intramedullary and one epidural,
      and review their MRI features. Diagnoses were established preoperatively in all
      cases. Specific MRI features including the importance of postgadolinium fat
      saturated T1-weighted images and presence of vascular flow-voids are discussed
      with histopathological correlation. A characteristic morphological appearance of
      intramedullary angiolipoma has been suggested.

PMID- 11966596
TI  - Peritoneal mesothelioma: CT and MRI findings.
AB  - Two patients with histologically proven diagnosis of peritoneal mesothelioma are
      presented. Both patients had CT scans of the abdomen. The second patient was also
      examined with MRI.

PMID- 11966597
TI  - Gadolinium-enhanced computed tomographic aortography.
AB  - Radiographic contrast agents using gadolinium have a better safety profile and
      photoelectric effect than iodinated contrast, allowing use where iodinated
      contrast is contraindicated. A case of gadolinium-enhanced computed tomographic
      aortography (CTA) for suspected thoracic dissection is reported. Aortic
      enhancement was sufficient for confident exclusion of an intimal flap. The
      findings were later confirmed by MRI. Vascular enhancement diminished below the
      diaphragm and tissue enhancement was minimal. Gadolinium diethylenetriamine penta
      acetic acid (Gd-DTPA) may be used for CTA of the thoracic aorta, where the use of
      iodinated contrast is contraindicated. Multi-slice CT may expand the role of
      gadolinium enhancement in the future.

PMID- 11966598
TI  - Posterior urethral valves causing urinomas: two case reports.
AB  - The cases of two male babies with posterior urethral valves complicated by the
      formation of urinomas are reported. Early diagnosis and treatment of this
      condition is important, as morbidity and mortality from resultant renal failure
      can be significant if it is unrecognized.

PMID- 11966599
TI  - Spontaneous regression of pulmonary bullae.
AB  - The natural history of pulmonary bullae is often characterized by gradual,
      progressive enlargement. Spontaneous regression of bullae is, however, very rare.
      We report a case in which complete resolution of pulmonary bullae in the left
      upper lung occurred spontaneously.

PMID- 11966600
TI  - Renal involvement in multifocal osteosarcoma.
AB  - A rare case of multifocal osteosarcoma metastatic to kidney, lung and lymph nodes
      is presented. Radiological findings included multiple foci of sclerotic lesions
      involving the axial and peripheral skeleton, a heterogeneous renal mass with
      areas of calcification, multiple pulmonary metastases with pneumothorax, and
      partially calcified enlarged mediastinal and abdominal lymph nodes.

PMID- 11966601
TI  - Use of endoscopic mucosal clips in radiotherapy planning for oesophageal
      carcinoma: a series of three cases.
AB  - This paper describes the technique of placing endoscopic mucosal clips to
      localize oesophageal carcinoma and hence facilitate radiotherapy planning. This
      technique has been used on three patients in our centre. One was treated
      radically with external beam radiotherapy and two were treated palliatively
      (retreatment) with intraluminal brachytherapy. Mucosal hemoclips were placed at
      the time of endoscopy to indicate the superior and inferior extent of the tumour.
      The clips provided a radiologically-recognisable marker of the tumour extent and
      were visible on simulation films or planning CT scans. The radiation portal
      included the tumour as demarcated by the clips with an adequate margin. There
      were no complications related to the placement of the clips. All patients
      completed the radiotherapy course as planned.

PMID- 11966602
TI  - Giant bleeding renal angiomyolipoma: diagnosis and management.
AB  - A case of a giant bleeding renal angiomyolipoma is presented. The patient was a
      40-year-old Egyptian male with no clinical or radiological evidence of tuberous
      sclerosis. The radiological features and management, including the role of
      angiography are briefly discussed and the medical reviews on this subject are
      briefly considered.

PMID- 11966603
TI  - Orbital multiple myeloma: case report and review of computed tomography features.
AB  - Orbital involvement at diagnosis in multiple myeloma is rare. Only a few a cases
      are reported with computed tomographic features. We report a case of orbital
      myeloma, and relevant medical reviews on computed tomography features are
      discussed.

PMID- 11966604
TI  - Beginning angiography: a step-by-step guide.
AB  - Procedures in radiology are still very much learnt as an apprenticeship. While
      there is no substitute for hands-on practice and the one-to-one teaching of an
      experienced consultant, it has been our experience that learning is significantly
      facilitated by the availability of simple, easy-to-follow, relevant notes for pre
      reading, especially in the difficult and potentially hazardous area of
      angiography. However, we have had surprising difficulty in finding an
      introductory text that is suitable for the teaching of angiography to new, never
      seen-it-before trainees. We have therefore developed a short, simple, illustrated
      manual within our department for introducing angiography to first-year
      registrars, which we present in this article. We hope trainees will find it of
      use for providing an overview of the principles and the basic techniques involved
      prior to beginning formal training in this challenging and rewarding specialty.

PMID- 11966605
TI  - Case quiz. Intracystic papillary carcinoma of the breast.

PMID- 11966606
TI  - John Martin Bradley (1925-2000).

PMID- 11966610
TI  - Rectal perforation during double contrast barium enema.

PMID- 11966619
TI  - Endoscopy through the ages.

PMID- 11966620
TI  - Re-auditing a regional lithotripsy service.
AB  - OBJECTIVE: To assess, in a repeat audit of a regional lithotripsy service,
      whether changes implemented after a regional audit in 1994 (which showed
      disappointing results from shock wave lithotripsy, attributable to both poor
      patient selection and an inadequate fixed-site lithotripter) have had any effect.
      PATIENTS AND METHODS: A data-collection sheet was devised to gather information
      on the site, size and number of stones treated, together with information on the
      lithotripsy treatment and outcome. Patients selected for the audit were the first
      50 new patients treated with lithotripsy at each centre in 1999. As only one
      hospital has a fixed-site lithotripsy machine, the results of mobile lithotripsy
      were grouped by machine for analysis. RESULTS: There was an overall improvement
      in patient selection from the previous audits. Few stones of > 16 mm or < 4 mm
      were treated. Two units treated more ureteric stones, thought to reflect first
      the influence of a fixed-site lithotripter, and second a willingness to insert a
      ureteric stent and await the next mobile lithotripter visit. The stone free rates
      were all disappointingly low (16.7-26.7%) but the results improved when fragments
      of < 4 mm were included as "successful" giving an "overall success rate" of 45.9
      66.7%. The unit with a fixed-site lithotripter appeared to perform better (two
      thirds successful) than the mobile machines (Modulith SLX, 51%; Modulith SLK,
      46%). One centre visited by both mobile machines had a success rate of 65% but a
      high rate of auxiliary procedures (35% vs 16-19% vs the fixed-site). CONCLUSION:
      Although these results show some improvement in patient selection for our
      regional lithotripsy service, stone-free and success rates are poorer than those
      reported elsewhere. This may reflect the modern lithotripsy machines that allow
      day-case treatment with minimal analgesia, and confirms reports by other authors
      who encourage a re-examination of success rates of shock wave lithotripsy.

PMID- 11966621
TI  - Magnetic resonance urography in patients with neurogenic bladder dysfunction and
      spinal dysraphism.
AB  - OBJECTIVE: To investigate the reliability of magnetic resonance urography (MRU)
      using heavily T2-weighted very fast spin-echo sequences in imaging the upper
      urinary tract in patients with spinal dysraphism and neuropathic bladder
      dysfunction. PATIENTS AND METHODS: Patients with neuropathic bladder dysfunction
      secondary to spinal dysraphism may have gross spinal deformity, which makes
      assessing the urinary tract extremely difficult by ultrasonography or intravenous
      urography. The study included 50 patients (median age 33 years, range 19-52) with
      a median (range) Cobb's angle of 60 (0-240) degrees. No contrast medium was given
      but all patients received 20 mg of intramuscular frusemide 20-30 min before MRU.
      RESULTS: Thirty-five patients had previous ultrasonography, during which only 42
      kidneys and no ureters were visible. Of the 94 renal tracts, MRU visualized all
      kidneys and 86 (89%) ureters. There was good agreement amongst observers on
      assessing the kidneys and pelvicalyceal systems (kappa > or = 0.61) but only
      moderate agreement on evaluating the ureters (kappa < or = 0.61). There was
      disagreement on normality vs renal parenchymal scarring in 14 (15%) kidneys,
      about no dilatation vs dilatation of the pelvicalyceal system in 14 (15%) systems
      and about no dilatation vs dilatation of the ureter in 20 (22%) ureters. The
      overall quality of the MRU images was rated highly, with a mean (range) score of
      4.6 (3-5). CONCLUSION: MRU provides a reliable noninvasive technique for imaging
      the upper tract in patients who were previously difficult to investigate.

PMID- 11966622
TI  - Photodynamic therapy for superficial bladder cancer under local anaesthetic.
AB  - OBJECTIVES: To evaluate the use of local anaesthesia (LA) in 5-aminolaevulinic
      acid (ALA) photodynamic therapy (PDT) for superficial transitional cell carcinoma
      (TCC) of the bladder, and to provide further toxicity and tolerability data on
      this new method within the context of a phase 1 trial. PATIENTS AND METHODS: ALA
      PDT was administered to 19 patients with recurrent superficial TCC (stage
      Ta/carcinoma in situ, grades 1-3) using escalating doses of ALA (3-6%) and 633 nm
      laser light (25-50 J/cm2) under various LA (lignocaine) protocols. Pain was
      assessed using a linear analogue scale from 0 to 10. The endpoints of
      tolerability and toxicity were assessed for the different LA, light and ALA
      doses, with lignocaine levels. RESULTS: ALA PDT is painful and requires some form
      of anaesthesia. The discomfort was immediate, associated with bladder spasm, and
      was a function of the ALA concentration rather than the total light dose given.
      Simple passive diffusion (PD) of 2% lignocaine instilled for 40 min before PDT
      gave adequate anaesthesia with 3% ALA (n=8; median pain score 1, range 0-2). With
      6% ALA the pain was dramatically increased using PD (n=6; median pain score 8,
      range 5-10) and therefore the more potent LA technique of electromotive drug
      administration (EMDA) of 2% lignocaine was used, with excellent results (n=3;
      median pain score 1, range 0-2). All patients had transient bladder irritability
      that typically lasted 9-12 days, with no subjective/objective change in long-term
      bladder function. No other toxicity was reported. Serum lignocaine levels were
      minimal. CONCLUSION: Bladder ALA PDT is both safe and feasible under LA. At a
      dose of 3% ALA, the procedure was well-tolerated using PD of lignocaine. At
      higher doses (6% ALA) more effective anaesthesia is required and this can be
      obtained satisfactorily with EMDA of lignocaine. With refinement, ALA PDT may be
      feasible as an outpatient treatment for superficial bladder TCC.

PMID- 11966623
TI  - Long-term follow-up of a randomized prospective trial comparing a standard 81 mg
      dose of intravesical bacille Calmette-Guerin with a reduced dose of 27 mg in
      superficial bladder cancer.
AB  - OBJECTIVES: To determine the efficacy of a three-fold reduced dose (RD, 27 mg) of
      intravesical bacille Calmette-Guerin (BCG) against the standard dose (81 mg) in
      patients with superficial bladder cancer, assessing recurrence, progression and
      differences in toxicity. PATIENTS AND METHODS: Five hundred patients with
      superficial bladder cancer (Ta, T1, Tis) were enrolled and randomly assigned to
      be treated after transurethral resection of all visible lesions with intravesical
      BCG Connaught strain (weekly x six and thereafter fortnightly x six) either with
      the standard or RD instillation. RESULTS: All but one of the 500 patients were
      evaluable for efficacy and toxicity (252 in the standard arm and 247 in the RD
      arm). The median follow-up was 69 months (maximum 104); 71 (28%) patients in the
      standard arm and 76 (31%) in the RD arm developed recurrences; the median time to
      recurrence has not yet been attained, but at 5 years the mean (sd) percentage of
      recurrence-free patients was 70.5 (3.12) and 70.4 (3.1) for the standard and RD
      arms, respectively. In patients presenting with multifocal tumours, the standard
      dose was more effective against recurrences than the RD (P=0.0151). In those with
      G3 and high-risk tumours overall, the superiority of the standard dose was
      marginal (P=0.060 and P=0.082). Twenty-nine (11.5%) tumours in the standard arm
      and 33 (13.3%) in the RD arm progressed to invasive disease; the median time to
      progression has not yet been attained, but the percentage of progression-free
      patients at 5 years was 88.8 (2.23) and 86.9 (2.31) for the standard and RD arms,
      respectively. The standard dose was more effective than the RD against
      progression only in patients with multifocal disease (P=0.048). Twelve (4.8%)
      cystectomies were performed in the standard and 15 (6.1%) in the RD arm.
      Currently, 106 (21.2%) patients have died, but only 38 (7.6%) from bladder
      cancer, i.e. 20 (7.9%) in the standard and 18 (7.5%) in RD arm. Overall the
      disease-specific death rate was lower for those patients who completed the
      scheduled treatment. The cause-specific survival at 5 years did not differ
      between the arms (P=0.76) but there was a trend toward better cause-specific
      survival for patients with multifocal tumours in the standard arm. Toxicity
      differed between the arms, significantly more patients having no toxicity in the
      RD arm, and fewer having delayed instillations or withdrawing. However, severe
      systemic toxicity occurred even in patients treated with the RD, in a similar
      proportion to those receiving the standard dose. CONCLUSION: Overall, the RD gave
      similar results for recurrence and progression but with significantly less
      toxicity. However, patients with multifocal tumours fared better with the
      standard dose and there was a trend towards better recurrence rates in patients
      with high-risk tumours. We recommend continuing to use the standard dose for high
      risk tumours, while we consider the reduced dose safe and effective for
      intermediate-risk lesions and for maintenance schedules.

PMID- 11966624
TI  - A randomized comparative dose-ranging study of interferon-alpha and mitomycin-C
      as an internal control in primary or recurrent superficial transitional cell
      carcinoma of the bladder.
AB  - OBJECTIVE: To compare, in a phase II study, the activity and toxicity of three
      dose levels of interferon-alpha, and of mitomycin-C given intravesically (as an
      internal control to validate the results), the primary objective being to
      investigate the percentage of complete responses (complete disappearance of a
      marker lesion) induced by the three interferon-alpha dose levels on a marker
      lesion; a secondary objective was to compare the interferon-alpha doses for
      toxicity. PATIENTS AND METHODS: In all, 115 patients were enrolled, with the
      inclusion criteria being multiple grade 1 or 2, stage Ta or T1, primary or
      recurrent transitional cell carcinoma of the bladder. Interferon-alpha (30, 50
      and 80 MU) and mitomycin-C (40 mg) intravesical treatments were given as follows.
      Patients randomized to one of three interferon-alpha dose levels were treated
      weekly for 12 weeks. However, in week 9 (first cystoscopy after baseline)
      interferon-alpha treatment was stopped if there was a complete response or
      disease progression. Patients randomized to mitomycin-C were treated weekly for 8
      weeks only and in week 9 underwent follow-up cystoscopy. RESULTS: Interferon
      alpha at doses of 30, 50 and 80 MU gave response rates at 13 weeks of 19%, 33%
      and 41%, respectively. Although the response rates were higher for 50 and 80 MU
      than for 30 MU, the differences were not statistically significant. All three
      interferon-alpha groups had significantly lower response rates than the internal
      control, mitomycin-C (72%). The safety analysis showed that most of the adverse
      events were of mild to moderate severity. Adverse events were experienced by 37%,
      37% and 48% of patients receiving 30, 50 and 80 MU interferon-alpha,
      respectively, and by 55% of patients receiving mitomycin-C. The corresponding
      rates for severe adverse events related to treatment were 9% for interferon-alpha
      and 10% for mitomycin-C. CONCLUSION: Ablative therapy with interferon-alpha was
      less effective than mitomycin-C in patients with superficial bladder cancer. Both
      drugs were well tolerated, although interferon-alpha appeared to have a slightly
      better overall safety profile.

PMID- 11966625
TI  - The tension-free vaginal tape for treating female stress urinary incontinence.

PMID- 11966626
TI  - Does the tension-free vaginal tape procedure affect the voiding phase? Pressure
      flow studies before and 1 year after surgery.
AB  - OBJECTIVE: To evaluate the voiding phase before and 1 year after surgery in women
      who underwent a tension-free vaginal tape (TVT) procedure for stress
      incontinence. PATIENTS AND METHODS: The study comprised 45 women with genuine
      stress urinary incontinence. To assess the voiding phase, patients were asked if
      their voiding had changed after surgery, and objectively the uroflowmetry,
      residual urine measurements and pressure-flow data were compared. RESULTS: At 1
      year after surgery 39 women (87%) were subjectively cured and six (13%) improved.
      The objective cure rate was 88%; the pad-test leakage and the number of leakage
      episodes decreased significantly after surgery. Subjectively, 78% of the patients
      reported that the voiding phase had become more difficult, and the spontaneous
      flow curve changed to a more obstructive pattern in 40%, with the mean urinary
      peak flow rate (Q(max)), the corrected Q(max) and the mean average flow rate
      decreasing significantly. The residual urine volume increased significantly,
      although no patient had volumes of > 25% of their bladder capacity. During the
      pressure-flow study the Q(max) decreased and the urethral resistance factor
      increased significantly. However, only one patient could be classified as
      obstructed. Two patients had clinical problems and used self-catheterization once
      daily 1 year after surgery. CONCLUSION: There were subjective and objective
      changes in the voiding phase 1 year after the TVT procedure. The significance of
      these findings remains to be determined. Longitudinal studies are warranted to
      clarify whether the patients at risk can be characterized from subjective and
      objective findings.

PMID- 11966627
TI  - Stromal and acinar components of the transition zone in normal and hyperplastic
      human prostate.
AB  - OBJECTIVE: To analyse the histological components of the transition zone in both
      normal human prostate and benign prostatic hyperplasia (BPH), and to determine
      the volumetric density (Vv) of the different elements (connective tissue, smooth
      muscle cells, acini and total stroma). MATERIALS AND METHODS: Samples of BPH
      tissue from the transition zone were obtained from 16 patients with clinical
      symptoms of bladder outlet obstruction who underwent open prostatectomy. The
      control samples comprised 16 transition zone samples from prostates obtained
      during necropsy of adults aged < 30 years (killed in accidents). The Vv of these
      components was determined by stereological methods. RESULTS: The mean (sd) Vv in
      the controls and BPH samples were, respectively: connective tissue 40.47 (5.16)
      and 46.71 (9.91)%; smooth muscle cells 24.86 (2.74) and 31.56 (5.49)%; acini
      28.73 (6.25) and 17.78 (10.87)%; all differences were statistically significant.
      CONCLUSIONS: These results confirm the hypothesis that in BPH there is an
      increase in the stromal component, both smooth muscle fibres and connective
      tissue.

PMID- 11966628
TI  - The role of serial free/total prostate-specific antigen ratios in a watchful
      observation protocol for men with localized prostate cancer.
AB  - OBJECTIVE: To examine the change in the free/total prostate specific antigen
      ratio (f/tPSA) with time and to assess the potential value of serial measurements
      of f/tPSA as a determinant of disease progression in untreated, low-to
      intermediate grade prostate cancer (T1b-T2b N0M0, Gleason score < or = 7 and PSA
      < or = 15 ng/mL). PATIENTS AND METHODS: In a prospective single-arm cohort study
      from November 1995, patients were conservatively managed with watchful
      observation alone unless they met arbitrarily defined criteria (clinical,
      histological and biochemical) of disease progression. Patients were followed
      regularly and underwent blood tests including PSA and f/tPSA. The initial and
      mean f/tPSA and the rate of change of f/tPSA with time were evaluated against the
      rate constant for the PSA doubling time (PSATd). Correlation analyses were used
      to evaluate any association between baseline clinical variables and either the
      rate of change of f/tPSA or initial f/tPSA. RESULTS: As of December 2000, 161 of
      a total of 206 accrued patients had three or more f/tPSA measurements and formed
      the basis of the study (median age 70 years; median follow-up 2.7 years). The
      median initial f/tPSA was 0.16; there was a significant negative correlation
      between this value and the initial total PSA. The mean f/tPSA and rate of change
      of f/tPSA with time were significantly negatively correlated with the rate
      constant for PSATd. Also, the rate of change of f/tPSA correlated negatively with
      clinical T stage, but not with other baseline variables, including initial PSA,
      age and Gleason score. CONCLUSION: The f/tPSA in men with untreated, clinically
      localized prostate cancer varied widely. The negative correlation between the
      rate of change of f/tPSA with time and rate constant for PSATd suggests that both
      might provide valuable information to allow clinicians to develop a strategy for
      optimizing the timing of therapeutic intervention for those patients choosing
      watchful observation alone.

PMID- 11966629
TI  - The correlation between pretreatment serum hormone levels and treatment outcome
      for patients with prostatic cancer and bony metastasis.
AB  - OBJECTIVE: To evaluate whether pretreatment serum hormone levels are a prognostic
      factor for prostatic cancer with bony metastasis under hormonal treatment.
      PATIENTS AND METHODS: Between 1980 and 1994, 96 patients with prostate cancer and
      bony metastasis were included for an evaluation by a retrospective review of
      their charts. All 96 had received hormonal treatment after a diagnosis of
      metastatic prostatic carcinoma. Serum testosterone, luteinizing hormone (LH),
      follicle-stimulating hormone (FSH) and prolactin were assessed before treatment.
      The patients were divided into two groups according to their response during the
      follow-up. Group 1 (good response) had no change or resolution of metastatic
      lesion(s) on the bone scan and a declining prostate-specific antigen (PSA) level.
      Group 2 had increased PSA or progression of metastatic lesion(s) on the bone
      scan. Tumours were graded as low (2-4), intermediate (5-7) and high (8-10) using
      the Gleason score. RESULTS: There were 43 patients in group 1 and 53 in group 2;
      the overall mean (sd) age was 72.5 (6.8) years and the follow-up 29.5 (0.5)
      months. The respective mean (sd) levels of testosterone, LH, FSH and prolactin
      before treatment were 4.6 (1.6) ng/mL, 20.2 (13.3) mIU/mL, 19.6 (18.6) mIU/mL and
      20.7 (12.1) ng/mL in group 1, and 2.6 (1.0) ng/mL, 27.3 (11.0) mIU/mL, 27.1 (9.8)
      mIU/mL and 41.3 (28.4) ng/mL in group 2. The level of testosterone was
      significantly higher in group 1 than in group 2, while LH, FSH and prolactin were
      significantly lower in group 1 than in group 2. When stratified by tumour grade,
      patients in group 1 still had significantly higher pretreatment testosterone and
      lower LH, FSH and prolactin than those in group 2. CONCLUSION: Higher
      testosterone and lower LH, FSH and prolactin levels were good prognostic factors
      for patients with metastatic prostatic cancer under hormonal treatment,
      irrespective of tumour grading.

PMID- 11966630
TI  - Biofeedback vs verbal feedback as learning tools for pelvic muscle exercises in
      the early management of urinary incontinence after radical prostatectomy.
AB  - OBJECTIVE: To evaluate the comparative effectiveness of electromyographic (EMG)
      biofeedback with verbal instructions as learning tools of pelvic muscle exercises
      (PMEs) in the early management of urinary incontinence after radical
      prostatectomy. PATIENTS AND METHODS: Forty-two consecutive patients (mean age 64
      years, sd 4.2), with urinary incontinence after radical retropubic prostatectomy
      for localized prostate cancer, were randomized to receive biofeedback (group A,
      28 men) or verbal feedback (group B, 14 men) as learning tools for PMEs
      immediately after catheter removal. Group A received 15 sessions of EMG
      biofeedback (three times weekly, 30 min each) and group B verbal instructions.
      Evaluation at baseline and 1, 2, 3 and 6 months included the 1-h pad-test and a
      questionnaire (number of pads/day and incontinence episodes). RESULTS: By the
      last follow-up, 27 patients had received biofeedback and 15 verbal instructions.
      Data were analysed according to the intention-to-treat principle. Urine loss as
      assessed by the 1-h pad-test at baseline, 1, 2, 3 and 6 months was 39, 18, 7, 4
      and 3 g for group A and 31, 11, 3, 1 and 0 g for group B, respectively (P >
      0.05). The number of pads/day was 3.9, 3.4, 1.2, 0.8 and 0.4 for group A and 3.6,
      1.8, 0.9, 0.4 and 0.2 for group B, respectively (P > 0.05). The overall
      continence rate at 6 months was objectively (urine loss > 1 g) 91% and
      subjectively (0-1 pad/day) 95%. CONCLUSION: Intensive verbal instructions and
      biofeedback were both very effective behavioural methods and learning tools for
      PMEs in the early management of urinary incontinence after radical prostatectomy.

PMID- 11966631
TI  - The anocutaneous reflex and urinary continence in children with myelomeningocele.
AB  - OBJECTIVE: To examine the hypothesis that because most patients with
      myelomeningocele and a positive anocutaneous reflex have a competent sphincteric
      mechanism they are more likely to be continent on intermittent catheterization
      than those with a negative reflex, and to become so with less need for adjunctive
      surgical treatment. PATIENTS AND METHODS: The study included 111 patients with
      myelomeningocele treated for urinary incontinence; their present means of
      treatment and the outcome achieved were assessed and related to the presence or
      absence of an anocutaneous reflex. RESULTS: Among 29 patients with a positive
      anocutaneous reflex, 26 (90%) are currently dry on a regimen of intermittent
      catheterization, as opposed 41 (50%) of the 82 with a negative reflex (P <
      0.001). Two (7%) of those with a positive and 23 (28%) of those with a negative
      reflex have undergone adjunctive surgery (P=0.024). CONCLUSION: These findings
      are consistent with both aspects of the hypothesis detailed in the Objective.

PMID- 11966632
TI  - Catheter-less Cohen transtrigonal ureteric reimplantation.
AB  - OBJECTIVE: To review the profile and outcome of patients in whom it was elected
      not to insert a bladder catheter as part of the management of Cohen transtrigonal
      ureteric reimplantation surgery. PATIENTS AND METHODS: Between April 2000 and
      April 2001, 37 patients underwent ureteric reimplantation by the senior author,
      using the Cohen transtrigonal technique. The use of the catheter-less protocol
      began after the blockage of a suprapubic catheter soon after surgery; the
      catheter was removed with no adverse event. Subsequently, 27 of those undergoing
      ureteric reimplantation were selected not to have a bladder catheter. Later in
      the study a greater proportion of patients had no catheter inserted, as
      confidence with the catheter-less technique increased. Caudal anaesthetic, oral
      analgesia and a single dose of intravesical bupivacaine were used for pain
      relief. The children were monitored closely after surgery and a urethral catheter
      inserted in the one patient who had not voided after 6 h. RESULTS: The patients
      generally tolerated the lack of a bladder catheter well. Of the 27 patients who
      did not have a catheter inserted at surgery, one required catheterization (a girl
      with bilateral duplex systems and large ureteroceles). Two children stayed in
      hospital for 2 days after surgery, one was discharged on the day of surgery, and
      the remainder went home on oral analgesia on the first day after surgery. Since
      starting the catheter-less approach, 10 patients have had a suprapubic catheter
      because they had more complex surgery, were older or because the approach had not
      developed sufficiently at the time of surgery. CONCLUSIONS: Intravesical ureteric
      reimplantation is not only safe when omitting a bladder catheter but, if used
      selectively, there appears to be a significant decrease in the hospital stay and
      discomfort after surgery.

PMID- 11966633
TI  - The cloacal plate: the missing link in anorectal and urogenital development.
AB  - OBJECTIVE: To determine whether differences in the embryology of the anorectal
      and urogenital area, previously examined in sheep, pigs, rats, rabbits and guinea
      pigs, producing varying conclusions, may be secondary to differences in species
      development. MATERIALS AND METHODS: Rat and human embryos were studied at the
      time of genital tubercle development and cloacal partition by standard serial
      section histology, and by immunohistochemistry, dissection and scanning electron
      microscopy. The images obtained were compared with those previously reported for
      pig and sheep embryos. RESULTS: The cloacal plate, a vertically orientated
      midline plate of epithelial cells in the caudal half of the genital tubercle, was
      the key structure that varied between the different species. In rats the plate
      maintained a vertical height along its length, while in humans and pigs it
      reverted to a two-layer membrane dorsally, shortly before it degenerated to
      expose both the anorectal and urogenital tracts. In sheep the plate was taller
      ventrally than in the other species but also reverted to a short membrane
      dorsally that exposed the hindgut when it degenerated. The anterior part of the
      cloacal plate persisted in all embryos as the urethral plate, which then
      participated in the formation of the urethra in the male and the vestibule in the
      female. The animal that most closely resembled humans in anogenital development
      was the pig. CONCLUSIONS: The cloacal plate is the key to understanding early
      anorectal and urogenital development and yet it is barely recognized in published
      reports. An appreciation of its relevance helps to explain the variations in the
      described embryology of the region, and is mandatory when interpreting
      embryological findings in animal models of human anomalies. Given the
      similarities between porcine and human development, the pig may be the most
      legitimate animal model for the study of anorectal and urogenital anomalies in
      humans.

PMID- 11966635
TI  - Severe partial ureteric obstruction in newborn rats can produce renal dysplasia.
AB  - OBJECTIVE: To investigate whether partial unilateral ureteric obstruction (PUUO)
      produces renal dysplasia in newborn rats. MATERIALS AND METHODS: Left mild (in
      31) or severe (in 34) PUUO was induced in 2-day-old rats by embedding a quarter
      or two-thirds of the ureter into the psoas muscles, respectively. Sham-operated
      control rats (36) were assessed in parallel. Kidney morphology, renal parenchymal
      weight and histology were examined 24 weeks and 30 months afterward. RESULTS:
      There was significant pelvic dilatation in all obstructed kidneys; four kidneys
      were dysplastic in those severely obstructed, with a significant decrease in
      renal volume. There were three dysplastic kidneys after 6 months and one at 30
      months. The in vitro dysplastic kidney weight was 36% of the control kidneys.
      Microscopy showed primitive glomerular and tubular structures, with renal
      parenchymal developmental disorganization and marked fibrosis. The glomeruli,
      tubules and collecting ducts were deficient in number and had often undergone
      cystic changes. Columnar tubular epithelium and peritubular mesenchymal collars
      were present. There was no renal dysplasia in the mildly obstructed and sham
      operated rats. The parenchymal weight of the kidneys contralateral to the
      dysplastic kidneys was significantly higher than in the controls (P < 0.001).
      CONCLUSIONS: Severe PUUO can produce renal dysplasia in newborn rats. However,
      only 12% with severe obstruction had renal dysplasia, indicating that the cause
      of renal dysplasia might also be related to other factors.

PMID- 11966634
TI  - The urethral plate--does it grow into the genital tubercle or within it?
AB  - OBJECTIVE: To determine whether the urethral plate grows into the genital
      tubercle or develops within it. MATERIALS AND METHODS: Sprague-Dawley rat embryos
      were examined at 11-21 days of gestation and compared with available human embryo
      sections. Rat embryos were examined by a combination of light microscopy,
      dissection, serial histological section and immunohistochemistry. RESULTS: In rat
      embryos the urethral plate extended to the tip of the genital tubercle from the
      earliest stages of genital tubercle development. The plate formed from adherence
      in the sagittal plane of the inner walls of the primitive cloacal cavity. The
      urethral plate continued to extend to the tip of the genital tubercle throughout
      penile development in the male and developed a lumen ahead of the advancing
      perineal mesenchyme. In the female the perineal side of the urethral plate
      disintegrated by massive apoptosis. This loss of perineal substance allowed the
      genital tubercle to collapse on itself and left the urogenital opening at the
      base of the genital tubercle. Human embryos also showed the presence of the
      urethral plate at the tip of the genital tubercle throughout genital tubercle
      development. CONCLUSION: The urethral plate forms ab initio within the genital
      tubercle and extends to the tip; it does not grow into the genital tubercle as is
      often described. The contribution of ectodermal ingrowth to urethral development
      at the tip of the penis is minimal.

PMID- 11966636
TI  - The future of clinical urology in Germany.

PMID- 11966637
TI  - Renal and ureteric trauma: diagnosis and management in Poland.
AB  - OBJECTIVE: To analyse retrospectively kidney and ureteric injuries (the former
      often associated with multiple-organ trauma) and thus optimize diagnostic and
      treatment methods. PATIENTS AND METHODS: The records and details of kidney and
      ureteric injures treated between 1995 and 1999 in 61 urological departments in
      Poland were analysed. RESULTS: In all, 887 kidney injuries were analysed; blunt
      trauma comprised 97%, with most injuries classified as renal contusion and minor
      parenchymal damage (687 cases). Intravenous urography was used in 80% of the
      patients and computed tomography in only 20%. In all, 234 patients (26%)
      underwent surgery; nephrectomy was the most common surgical treatment, in 170
      patients (73% of those undergoing surgery). Complications occurred in 9% of
      patients after conservative treatment and in 5% after surgery. Of the 452
      ureteric injuries, 340 (75%) were iatrogenic, 81 (18%) blunt injuries and 31 (7%)
      open injuries. Of the iatrogenic injuries 73% occurred during gynaecological
      procedures, 14% in general surgery and 14% in urological procedures. The most
      frequent diagnostic method was intravenous urography (244 cases), with retrograde
      pyelography (98) and ureteric catheterization in 125. The diagnosis was
      established immediately during surgery in 104 patients. The most frequent
      surgical treatment was uretero-neocystostomy (213, 47%), the others being a Boari
      flap (113, 25%), end-to-end anastomosis (92, 20%), reconstruction with an ileal
      loop (30, 7%) and autotransplantation (four, 1%). CONCLUSION: In Poland, patients
      with blunt kidney injuries often undergo surgery, with nephrectomy the most
      frequent procedure. Computed tomography with the intravenous administration of
      contrast medium should be considered the diagnostic method of choice for kidney
      injures. Catheterization of the ureters before surgery and an indigocarmine
      intravenous infusion (to stain the urine) when a ureteric injury is suspected may
      reduce the rate of iatrogenic injury and improve the rate of intraoperative
      diagnosis. We suggest catheterizing the ureters in any doubtful case to avoid
      injury, because prevention is better than treatment.

PMID- 11966638
TI  - Treatment of posterior and anterior urethral trauma.
AB  - OBJECTIVE: To assess the occurrence and treatment of posterior urethral (most
      often caused by traffic accidents and comprising half of all cases of urinary
      tract traumas) and anterior urethral injury (usually iatrogenic during
      catheterization or cystoscopy, or caused by blunt trauma, e.g. straddle injury or
      penetrating trauma). PATIENTS AND METHODS: The records and details of patients
      with posterior and anterior urethral trauma were analysed from 61 urological
      departments in Poland between 1995 and 1999. RESULTS: During the 5-year period
      there were 268 cases of posterior and 255 of anterior urethral injury; for the
      former, most occurred during traffic accidents, and of the latter 206 were
      iatrogenic (during catheterization or cystoscopy), of which 48 were accompanied
      by perineal injury. The posterior injuries were isolated or involved many organs,
      mainly pelvic bones. Both types of injuries were diagnosed using ascending
      urethrography, voiding cysto-urethrography and urethroscopy/endoscopy. Treatment
      for posterior injuries included cystostomy alone or cystostomy with abdominal
      drainage or perineal drainage; some patients also had their urethra
      reconstructed. The treatment for anterior injuries was conservative in 193
      patients and surgical in 62. CONCLUSION: The early detection and appropriate
      surgical treatment of posterior and anterior urethral injury is crucial for the
      recovery of urethral function, and avoids many complications.

PMID- 11966639
TI  - External and iatrogenic trauma of the urinary bladder: a survey in Poland.
AB  - OBJECTIVE: To assess incidence of urinary bladder injuries (frequently associated
      with pelvic trauma and often iatrogenic) in Poland. MATERIALS AND METHODS: The
      records and details of urinary bladder injuries treated between 1995 and 1999
      were analysed for 61 urological departments in Poland. RESULTS: During the 5-year
      period 512 patients had urinary bladder injuries; in 210 (41%) the injury was
      caused by a road traffic accident, in eight (2%) by compression (crushing injury)
      within the limits of the pelvic bones, in 40 (8%) by a fall from a height, in
      three by a gunshot wound and in the remaining 251 (49%) the injury was
      iatrogenic. Among the 261 bladder injuries that were not iatrogenic, 41 (16%)
      were associated with pelvic bone trauma. In 36 patients there was simultaneous
      injury of the urinary bladder and posterior urethra, constituting 14% of such
      injuries and 7% of all trauma cases. The iatrogenic injuries were in 98 patients
      (39%) in urological departments, in 130 (52%) women in gynaecological departments
      and in 23 (9%) on surgical wards. The injury was open in 102 patients (20%) and
      closed in 372 (73%); there was bladder contusion in 38 patients (7%). The
      injuries were intraperitoneal in 225 patients (44%) and extraperitoneal in 287
      (56%). For diagnosis, abdominal ultrasonography was used in 455 (89%) patients,
      intravenous pyelography in 266 (52%), cystography in 388 (76%) and computed
      tomography in 15 (3%). The delay between trauma and diagnosis was 0.5-124 h.
      Surgical treatment of the injury comprised a monolayer suture of the bladder wall
      in 51 patients (10%), a two-layered suture in 461 (90%), perivesical drainage in
      468 (91%) and inspection of the peritoneal cavity in 232 (45%). The mean (range)
      interval between diagnosis and treatment was 14 (7-70) days. Seven patients died
      after the treatment failed. CONCLUSIONS: Almost half the patients had iatrogenic
      injuries, of which over half occurred in gynaecological and maternity wards. Thus
      it is important teach the basic range of urological operations to trainee
      doctors. The commonest diagnostic method was not ascending cystography but
      ultrasonography; we recommend ascending cystography be used with at least two
      views after filling the urinary bladder with approximately 300 mL of contrast
      medium, with an additional film after emptying the contrast medium. In patients
      with pelvic bone trauma it is reasonable to use spiral computed tomography with
      virtual analysis before surgery. A two-layered suture of the bladder wall with
      perivesical drainage should be used.

PMID- 11966640
TI  - Comparison of the bladder tumour antigen test with photodynamic diagnosis in
      patients with pathologically confirmed recurrent superficial urinary bladder
      tumours.
AB  - OBJECTIVE: To verify the sensitivity of the bladder tumour antigen (BTAstat, Bard
      Urological, Covington, GA) test against the sensitive procedure of photodynamic
      diagnosis (PDD), in which 5-aminolaevulinic acid (5-ALA, a precursor of
      fluorescent porphyrins) is absorbed by the tumour and detected by ultraviolet
      cystoscopy, in the early diagnosis of urinary bladder tumours. PATIENTS AND
      METHODS: Forty-three patients (31 men and 12 women, age range 21-87 years) were
      assessed after transurethral resection of their bladder tumour using the BTAstat
      test and PDD. Sixty-nine biopsies from suspect areas of bladder mucosa were taken
      during cystoscopy under ultraviolet light and all suspect lesions
      electrocoagulated. RESULTS: Thirty-five patients (81%) had a positive BTAstat
      test; in these patients PDD detected malignant lesions (17 Ta1G1-2, two T1G2, two
      T1G3 and 14 Tis). In eight patients (19%) the BTAstat was negative but PDD
      detected three malignant lesions (two Tis and one TaG1). CONCLUSIONS: PDD is
      valuable for detecting bladder malignancy and can identify small lesions not
      detected by the BTAstat test.

PMID- 11966641
TI  - Hypericin-based fluorescence diagnosis of bladder carcinoma.
AB  - OBJECTIVE: To determine the use of hypericin instillation for the fluorescent
      detection of papillary bladder cancer and carcinoma in situ. PATIENTS AND
      METHODS: Eighty-seven patients with papillary bladder cancer and/or carcinoma in
      situ received instillations with 40 mL of an 8 micromol/L hypericin solution for
      at least 2 h. Fluorescent excitation with blue light was effective for up to 16
      h, and biopsies were examined by fluorescence microscopy. RESULTS: There were no
      side-effects reported, no photobleaching and all papillary lesions fluoresced
      red. The sensitivity and specificity for detecting carcinoma in situ was 94% and
      95%, respectively. An interval of 4 months is recommended after BCG instillations
      before using this test. Fluorescence microscopy showed that hypericin was
      selectively localized in the epithelium. CONCLUSIONS: Hypericin-induced
      fluorescence has a high sensitivity and specificity for detecting bladder cancer.
      After 4 months there are few false-positive results in patients treated with BCG.

PMID- 11966642
TI  - The diagnosis and management of vesicovaginal fistulae.

PMID- 11966643
TI  - Transurethral microwave thermotherapy: first experiences in Poland.
AB  - OBJECTIVE: To present early experiences in Poland with high-energy transurethral
      microwave thermotherapy (HeTUMT), considered as a serious alternative to surgery
      in managing benign prostatic hypertrophy (BPH). PATIENTS AND METHODS: Sixty-one
      patients were treated in two centres using a commercial TUMT system. The patients
      were assessed at 5-6 weeks, 3 and 6 months after treatment, evaluating subjective
      complaints, the International Prostate Symptom Score (IPSS), urinary flow rate
      and postvoid residual volume. RESULTS: A complete follow-up was available in 44
      patients; most had symptomatic improvement 3 months after HeTUMT but it was
      slightly less pronounced after 6 months. The improvement in objective variables
      increased up to 6 months after HeTUMT. There was > or = 50% improvement in
      subjective complaints in 43% of the patients, in urinary flow rate in 25% and in
      residual urine in half. Two patients required re-treatment for a urethral
      stricture and ineffective HeTUMT. CONCLUSIONS: HeTUMT may be a useful treatment
      for BPH but the outcome for an individual patient seems to be unpredictable. The
      indications for TUMT should be reviewed individually for each patient.

PMID- 11966644
TI  - The efficacy of terazosin for treating benign prostatic hyperplasia: a
      multicentre clinical trial.

PMID- 11966646
TI  - Microangiographic imaging of the prostate.
AB  - OBJECTIVE: To present the results of microangiography in visualizing prostatic
      microvascularization. MATERIALS AND METHODS: A contrast medium was injected into
      the vessels of prostate specimens obtained during surgery, to fill small vessels;
      nine specimens were obtained after cystoprostatectomy and two after radical
      prostatectomy. Branches of prostatic or seminal vesicle arteries were used for
      the injection, the specimens then fixed in formalin, sectioned and X-rayed.
      RESULTS: In five samples the quality of the images was sufficient to visualize
      small arteries; the remaining vessels were partially filled. The vascular map was
      compared with previous results from historadiographic studies. CONCLUSIONS:
      Microangiographic imaging of prostate specimens provides a unique view of the
      angioarchitecture of the prostate and correlates closely with historadiographic
      studies. The correlation with other imaging methods, e.g. Doppler
      ultrasonography, needs further evaluation.

PMID- 11966645
TI  - The therapy of benign prostatic hyperplasia using less-invasive procedures: the
      current situation.

PMID- 11966647
TI  - Usefulness of power Doppler ultrasonography in evaluating erectile dysfunction.
AB  - OBJECTIVE: To evaluate deep penile arterial flow after an intracavernosal
      injection with papaverine in patients with erectile dysfunction (ED). PATIENTS
      AND METHODS: Twenty patients with ED were evaluated using power Doppler
      ultrasonography with a linear probe (8 MHz). Diagnostic tests were undertaken
      after an intracavernosal injection with 40 mg papaverine. The peak systolic
      velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI) were
      analysed. RESULTS: After injecting papaverine, seven patients had a normal
      erection and appropriate waveform patterns; their mean PSV was 30.7 cm/s, the EDV
      4.42 cm/s and the RI 0.85. There was tumescence and elongation of the penis with
      no rigidity in eight patients; their mean PSV was 23.9 cm/s, the EDV 7.34 cm/s
      and the RI 0.72. There was no erection in five patients. The abnormal flow values
      showed insufficient arterial vessels in a quarter of the men, venous leakage in
      15% and mixed ED in 20%. CONCLUSION: The power Doppler technique allows the
      accurate location and evaluation of deep penile arteries. Vascular pathology may
      be differentiated after an intracavernosal injection with a vasomotor agent.
      Recognising the pathological pattern assists in choosing the best method of
      treatment.

PMID- 11966648
TI  - Surgery for idiopathic retroperitoneal fibrosis by ureterolysis and ureteric
      protection with a posterior pre-peritoneal fat flap.

PMID- 11966649
TI  - Acute renal artery occlusion in a 15-year-old girl taking oral contraceptives.

PMID- 11966650
TI  - Renal cell carcinoma presenting with hyperglycaemia.

PMID- 11966651
TI  - A 10-year experience of managing ureteric calculi: changing trends towards
      endourological intervention--is there a role for open surgery?

PMID- 11966653
TI  - Scintigraphic screening for renal damage in siblings of children with
      asymptomatic primary vesico-ureteric reflux.

PMID- 11966655
TI  - Chronic ethanol consumption impairs adrenoceptor- and purinoceptor-mediated
      relaxations in isolated rat detrusor smooth muscle.

PMID- 11966656
TI  - Interstitial cystitis--a time for revision of name and diagnostic criteria in the
      new millennium?

PMID- 11966657
TI  - Aberrant Foley catheter placement into the proximal right ureter.

PMID- 11966658
TI  - Interstitial cystitis--a time for revision of name and diagnostic criteria in the
      new millennium?

PMID- 11966663
TI  - What knowledge and skills are essential for specialists in Clinical Pharmacology
      and Therapeutics? Results of a Delphi study.
AB  - AIMS: To identify the knowledge and skills that should be considered essential
      for specialists in Clinical Pharmacology and Therapeutics (CPT) with a commitment
      to the National Health Service (NHS). METHODS: A Delphi study using a sample of
      current specialists. RESULTS: Members of the expert panel (20 in all,
      representative of the Clinical Section membership) identified 78 statements for
      consideration, in four domains (core of knowledge, therapeutic skills, educative
      skills, and investigative skills), of which 58 (74.4%) were accepted by more than
      two-thirds of respondents. Of these, 35 were knowledge items, whereas 23 were
      skills (11 therapeutic, 4 educative and 8 investigative). The large majority
      (79.3%) of these statements were endorsed by at least four out of five panel
      members. CONCLUSIONS: Despite the varied work patterns and responsibilities of
      specialists in CPT, it is possible to identify a core of knowledge and skill that
      most consider essential for the delivery of their commitment to the NHS. The
      findings will provide NHS Trusts with a clear idea of what they can expect from
      these specialists, and will act as a checklist for specialists themselves to
      direct their Continuing Professional Development within the consultant appraisal
      process. The results also describe a curriculum for continuing education in CPT,
      which the BPS Clinical Section can use to develop information resources and
      training opportunities.

PMID- 11966664
TI  - The bioavailability and pharmacokinetics of subcutaneous, nebulized and oral
      morphine-6-glucuronide.
AB  - AIMS: Morphine-6-glucuronide (M6G), one of the active metabolites of morphine,
      has attracted considerable interest as a potent opioid analgesic with an
      apparently superior therapeutic index. To date studies have used the intravenous
      route, which is generally unacceptable in the treatment of cancer related pain.
      The aim of this study was to define the pharmacokinetics, toxicity and cardio
      respiratory effects of three alternative routes of administration of M6G.
      METHODS: Ten healthy volunteers participated in an open randomized study.
      Subjects received M6G 2 mg as an intravenous bolus, 20 mg orally, 2 mg
      subcutaneously and 4 mg by the nebulized route. Pulse, blood pressure,
      respiratory rate and peak flow rate were monitored and subjective toxicity
      recorded on rating and visual analogue scales. RESULTS: After i.v. M6G the mean
      (+/- s.d.) AUC(0,infinity) standardized to a dose of 1 mg was 223 +/- 57 nmol l(
      1) h, mean elimination half-life was 1.7 +/- 0.7 h and the mean clearance was 157
      +/- 46 ml min(-1). These parameters were virtually identical after subcutaneous
      administration which had a bioavailability (F(0,infinity)) of 102 +/- 35% (90% CI
      82, 117%) and t(max) of 0.5 +/- 0.2 h. The mean bioavailability of nebulized M6G
      was 6 +/- 2% (90% CI 4, 7%) with a t(max) of 1.2 +/- 0.8 h. Following oral M6G
      two plasma M6G peaks were seen in 7 of the 10 subjects, the first with a t(max)
      of 3.1 (+/- 0.9) h. The second peak had a t(max) of 13.4 (+/-5.0) h, started
      approximately 4 h after dosing, and was associated with the detection of plasma
      M3G and morphine, suggesting that M6G was significantly hydrolysed in the gut to
      morphine, which was then glucuronidated following absorption. Although the
      overall mean bioavailability was 11 +/- 3% (90% CI 9, 12%), confining the
      analysis to data from the first peak suggested a bioavailability of directly
      absorbed M6G of only 4 +/- 4%. Apart from a characteristic dysphoria following
      intravenous and subcutaneous M6G, there was no significant toxicity. CONCLUSIONS:
      With the minimal toxicity reported in this and previous studies, subcutaneous
      infusion of M6G may potentially provide clinically useful analgesia for advanced
      cancer pain. Nebulized M6G is not significantly absorbed via the lungs, and if
      opiates are shown to have a local effect in the lung, reducing the sensation of
      breathlessness, then nebulized administration is likely to minimize systemic
      effects. Oral M6G has poor bioavailability, but is significantly hydrolysed in
      the gut to morphine, which is subsequently glucuronidated following absorption.
      This circuitous route accounts for the majority of systemically available M6G
      after oral administration.

PMID- 11966665
TI  - Pharmacokinetics and pharmacodynamics of tezosentan, an intravenous dual
      endothelin receptor antagonist, following chronic infusion in healthy subjects.
AB  - AIMS: The purpose of this study was to investigate the tolerability,
      pharmacokinetics, and pharmacodynamics of tezosentan, an intravenous dual
      endothelin receptor antagonist, during chronic infusions in healthy male
      subjects. METHODS: Tezosentan was infused at a rate of 100 mg h(-1) for 6 h
      (study A, six subjects) and at a rate of 5 mg h(-1) for 72 h (study B, eight
      subjects). Both studies had a randomized, placebo-controlled, double-blind
      design. Tolerability and safety were monitored by the recording of vital signs,
      ECG, adverse events and clinical laboratory parameters. Blood samples were
      collected frequently for pharmacokinetic determinations and measurement of plasma
      endothelin-1 concentrations. RESULTS: In both studies tezosentan was well
      tolerated with headache the most frequently reported adverse event (incidence of
      75-100% for tezosentan and 50% for placebo). Plasma concentrations of tezosentan
      rapidly approached steady state (3000 and 125 ng ml(-1) in study A and B,
      respectively) and did not change upon prolonged infusion. A two-compartment model
      could describe its pharmacokinetic profile. The half-lives of the two disposition
      phases were approximately 0.10 and 3.2 h. Endothelin-1 concentrations increased
      rapidly 11- and 2-fold compared with pre-dose values in study A and B,
      respectively, during infusion of tezosentan and did not change during the 72 h
      infusion. CONCLUSIONS: On the basis of these results, dose finding studies with
      tezosentan in acute heart failure can be initiated in the dose range 5-100 mg h(
      1).

PMID- 11966666
TI  - Association between antidepressant drug use and hyponatraemia: a case-control
      study.
AB  - AIMS: To estimate the risk of, and risk factors for, hyponatraemia associated
      with the use of selective serotonin reuptake inhibitors (SSRIs) compared with the
      use of other antidepressant drugs. METHODS: A case-control study of psychiatric
      in- and out-patients on antidepressant drugs performed in the mid-southern part
      of The Netherlands over a 2 year period. Cases (n=29) were all using
      antidepressant drugs with a serum sodium concentration of < or = 130 mmol l(-1)
      while controls (n=78) were patients on antidepressants with a normal sodium
      concentration (136-144 mmol l(-1)). Information on blood sodium concentrations
      was obtained from clinical chemistry data while information on drug use was
      obtained from community and hospital pharmacy databases. Medical records were
      used to ascertain possible risk and confounding factors. Unconditional
      multivariate logistic regression was used to estimate odds ratios for
      hyponatraemia in patients on SSRIs compared with patients on other antidepressant
      drugs. RESULTS: SSRIs were associated with an increased risk of hyponatraemia (OR
      3.3; 95% CI 1.3, 8.6) compared with other classes of antidepressant drugs.
      Stratified and interaction analyses revealed that elderly patients using
      diuretics concomitantly with SSRIs were at the highest risk of experiencing
      hyponatraemia (OR 13.5; 95% CI 1.8, 101). CONCLUSIONS: SSRIs are more frequently
      associated with hyponatraemia than other classes of antidepressant drugs. This
      adverse drug reaction was more common in older patients (> or = 65 years) and in
      those using diuretics.

PMID- 11966667
TI  - Non-sedating antihistamine drugs and cardiac arrhythmias -- biased risk estimates
      from spontaneous reporting systems?
AB  - AIMS: This study used spontaneous reports of adverse events to estimate the risk
      for developing cardiac arrhythmias due to the systemic use of non-sedating
      antihistamine drugs and compared the risk estimate before and after the
      regulatory action to recall the over-the-counter status of some of these drugs.
      METHODS: All suspected adverse drug reactions (ADRs) reported until July 1999 to
      the Netherlands Pharmacovigilance Foundation Lareb were used to calculate the ADR
      reporting odds ratio, defined as the ratio of exposure odds among reported
      arrhythmia cases, to the exposure odds of other ADRs (non-cases), adjusted for
      gender, age, reporter, year of reporting and comedication, stratified for the
      periods before and after the governmental decision in the Netherlands. RESULTS:
      Seven-hundred and thirty-seven cases of arrhythmia were reported, out of which
      there were 43 instances where the patients were using non-sedating
      antihistamines. In general non-sedating antihistamines are associated with
      cardiac arrhythmia to a higher extent in comparison with other drugs (ADR
      reporting odds ratio 2.05 [95% CI: 1.45, 2.89]). The association between
      arrhythmias and non-sedating antihistamine drugs calculated before 1998 was not
      significantly higher than 1 (OR 1.37 [95% CI: 0.85, 2.23]), whereas the risk
      estimate calculated after the governmental decision did significantly differ from
      1 (OR 4.19 [95% CI: 2.49, 7.05]). CONCLUSIONS: Our data suggest that non-sedating
      antihistamines might have an increased risk for inducing arrhythmias. Our
      findings, however, strongly suggest that the increased risk identified can at
      least partly be explained by reporting bias as a result of publications about and
      mass media attention for antihistamine induced arrhythmias.

PMID- 11966668
TI  - High persistence of statin use in a Danish population: compliance study 1993
      1998.
AB  - AIMS: Several studies have found that compliance with lipid-lowering drug (LLD)
      treatment is low. However, the results of these studies were based on crude
      measures of compliance. The aim of this study was to describe compliance with
      statin treatment by analysing prescription patterns on an individual level in a
      population-based prescription database over a 6 year period. METHODS: For
      incident statin users, all prescriptions for statins and drugs indicating
      cardiovascular disease or diabetes were retrieved from the OPED prescription
      database covering a population of about 470,000 inhabitants. Treatment was
      considered discontinued if the interval between two prescriptions exceeded number
      of tablets prescribed, plus 30 days. Compliance was assessed in terms of
      persistence and continuity. Persistence was defined as the period from the first
      prescription date to the date of discontinuation. Continuity was defined as the
      number of days with treatment (=number of tablets) divided by the total number of
      days in the period of persistence. RESULTS: 11% of the study cohort only received
      a single statin prescription. Survival analyses revealed a median persistence of
      41 months. Less than 15% of the patients had more than 20% days without therapy
      within the period of persistence. Patients under 45 years without drug indicators
      of cardiovascular disease or diabetes presented the lowest compliance.
      CONCLUSIONS: The study showed good compliance with statin treatment in terms of
      persistence and continuity. A high percentage of the youngest patients, however,
      seemed to discontinue treatment before obtaining the full benefit in terms of
      decreased risk of coronary heart morbidity and mortality.

PMID- 11966669
TI  - Time trends in lipid lowering drug use in The Netherlands. Has the backlog of
      candidates for treatment been eliminated?
AB  - AIMS: To assess time trends in lipid lowering drug use in The Netherlands.
      METHODS: Data were obtained from the PHARMO-database, comprising pharmacy records
      of approximately 300 000 people in The Netherlands. In the period from 1991-98,
      we estimated prevalence of lipid lowering drug use on the first Wednesday of
      October. A patient was defined as incident user if (s)he filled a prescription
      for lipid lowering medication after a 360 days lipid lowering drug free interval.
      Both prevalence and incidence estimates were weighted for the sex and age
      distribution of the general Dutch population. RESULTS: From 1991 to 1998, the
      prevalence of lipid lowering drug use increased from 0.5% (95% confidence
      interval (CI): 0.5, 0.6) to 2.3% (95% CI: 2.2, 2.4) in women and from 0.6% (95%
      CI: 0.6, 0.6) to 2.9% (95% CI: 2.8, 3.0) in men. Prevalence increased with
      increasing age and was highest in the age category 60-69 years (in 1998: 9.9%
      (95% CI: 9.4, 10.4) in women and 11.6% (95% CI: 11.0, 12.1) in men). In 1992, the
      estimated incidence of lipid lowering drug use was 251(95% CI: 226, 277)/100,000
      person years in women and 251(95% CI: 225, 276)/100,000 person years in men. The
      largest incidence estimates were observed in 1996 (685(95% CI: 644, 726)/100,000
      person years in women and 881(95% CI: 834, 928)/100,000 person years in men).
      After 1996, incidence stabilized in 1997 and decreased in 1998 to 599(561,
      637)/100,000 person years in women and 731(688, 773)/100,000 person years in men.
      Most of the patients (approximately 95%) were treated with one lipid lowering
      agent. Statins were used by over 90% of patients from 1996 onwards. In 1998, 35%
      of the patients started with a statin that was not a first choice drug (mainly
      atorvastatin). CONCLUSIONS: In the period from 1991-98, prevalence of lipid
      lowering drug use significantly increased in The Netherlands. However, incidence
      stabilized and decreased after 1996 which may be explained by the fact that the
      number of patients eligible for treatment was reached. The question remains
      whether lipid lowering medication was targeted to the appropriate patients.

PMID- 11966670
TI  - Pharmacokinetics of intravenous busulfan in children prior to stem cell
      transplantation.
AB  - AIMS: Intravenous formulations of busulfan have recently become available.
      Although busulfan is used frequently in children as part of a myeloablative
      regimen prior to bone marrow transplantation, pharmacokinetic data on intravenous
      busulfan in children are scarce. The aim was to investigate intravenous busulfan
      pharmacokinetics in children and to suggest a limited sampling strategy in order
      to determine busulfan systemic exposure with the minimum of inconvenience and
      risk for the patient. METHODS: Plasma pharmacokinetics after the first
      administration was investigated in six children using nonlinear mixed effect
      modelling. RESULTS: Pharmacokinetics showed little variability and were described
      adequately with a one-compartment model (population estimates CL,av=0.29 l h(-1)
      kg(-1); V,av=0.84 l kg(-1); t(1/2)=1.7-2.8 h). Combined with limited sampling and
      a Bayesian fitting procedure, the model can adequately estimate the systemic
      exposure to intravenous busulfan, which in children appears to be at the lower
      end of the adult range. CONCLUSIONS: Busulfan systemic exposure in children
      during intravenous administration can be estimated adequately with limited
      sampling and a Bayesian fitting procedure from a one-compartment model.
      Intravenous busulfan pharmacokinetics in children should be the subject of more
      research.

PMID- 11966671
TI  - Pharmacokinetics and metabolism of oral midazolam in preterm infants.
AB  - AIMS: To characterize the pharmacokinetics and metabolism of oral midazolam in 15
      preterm infants. METHODS: After an oral dose (0.1 mg kg(-1)), blood was drawn up
      to 24 h after administration. Midazolam and 1-OH-midazolam concentrations were
      determined with GC-MS. In 8 out of these 15 patients the pharmacokinetics of
      intravenous midazolam was also studied. RESULTS: Apparent oral clearance,
      apparent volume of distribution, plasma half-life and 1-OH-Midazolam/Midazolam
      AUC ratio were [median (range)]: 2.7 [0.67-15.5] ml kg(-1) min(-1), 1.4 [0.3
      12.1] l kg(-1), 7.6 [1.2-15.1], h and 0.03 [0.01-0.96], respectively. Absolute
      bioavailability was 0.49 [0.12-1.0]. CONCLUSIONS: Midazolam oral clearance is
      markedly decreased in preterm infants as compared with older children, probably
      because of immature CYP3A4 activity.

PMID- 11966672
TI  - Omeprazole hydroxylation is inhibited by a single dose of moclobemide in
      homozygotic EM genotype for CYP2C19.
AB  - AIMS: The pharmacokinetics of omeprazole and its metabolites in healthy subjects
      were evaluated to determine if a single dose of moclobemide inhibited CYP2C19
      activity. METHODS: Sixteen volunteers, of whom eight were extensive metabolizers
      (EM) and eight were poor metabolizers for CYP2C19, participated in two studies.
      Venous blood samples were collected for 24 h after oral ingestion of 40 mg
      omeprazole with or without 300 mg moclobemide coadministration. The
      pharmacokinetic change of omeprazole, omeprazole sulphone and 5-hydroxyomeprazole
      concentrations were assessed to test for an interaction between omeprazole and
      moclobemide. RESULTS: The coadministration of moclobemide in EMs approximately
      doubled the mean AUC (from 1834 to 3760 ng ml(-1) h) and C(max) (from 987 to 1649
      ng ml(-1)) of omeprazole, and increased the AUC of omeprazole sulphone without
      changing AUC ratio of omeprazole to omeprazole sulphone. Moclobemide
      coadministration more than doubled the AUC ratio of omeprazole to 5
      hydroxyomeprazole (from 2.5 to 5.3) in EMs, too. There was a significant decrease
      in Cmax and AUC of 5-hydroxyomeprazole in PMs but no significant changes were
      seen in the results for omeprazole and omeprazole sulphone AUCs. CONCLUSIONS: A
      single dose of moclobemide resulted in significant suppression of CYP2C19
      activity in EMs. We conclude that physicians prescribing moclobemide should pay
      attention to its pharmacokinetic interactions even on the first day of
      coadministration with CYP2C19 substrates.

PMID- 11966674
TI  - A possible interaction between lithium and rofecoxib.

PMID- 11966673
TI  - Serum cystatin C is not a better marker of creatinine or digoxin clearance than
      serum creatinine.
AB  - AIMS: To assess whether cystatin C, a new serum marker of renal function, is a
      better index of creatinine or digoxin clearance than serum creatinine in older
      people. METHODS: Twenty-two volunteers over the age of 65 years (mean 73 +/- 5)
      were recruited from a healthy elderly volunteer database. None of the volunteers
      was taking digoxin or other medication known to interfere with digoxin kinetics
      or assay. Digoxin was infused at a dose of 7-10 microg kg(-1) and blood samples
      were taken over the following 48 h and assayed for serum digoxin. Serum cystatin
      C, creatinine and creatinine clearance were measured and a calculated creatinine
      clearance was estimated using the Cockcroft Gault formula. Digoxin clearance was
      calculated using a pharmacokinetic software package. All values were log
      transformed to normalize their distribution. RESULTS: Of the 22 volunteers
      enrolled into the study, 18 completed the study. Serum cystatin C ranged between
      0.72 and 1.89 mg l(-1) and serum creatinine ranged from 69.6 to 153.9 micromol l(
      1). Measured creatinine clearance ranged from 38 to 123 ml min(-1) and calculated
      creatinine clearance from 29.5 to 88.0 ml min(-1). Digoxin clearance ranged from
      51.0 to 103.5 ml min(-1). Cystatin C correlated extremely well with creatinine
      (r=0.93, P<0.001, 95% CI 0.82, 0.97) and with creatinine clearance (r=0.67,
      P=0.002, 95% CI 0.3, 0.87). Neither serum cystatin C nor serum creatinine
      correlated with digoxin clearance (r=0.25, P=0.31, 95% CI -0.25, 0.64 and r=0.44,
      P=0.068, 95% CI -0.03, 0.75, respectively). Measured creatinine clearance,
      however, did correlate well with digoxin clearance (r=0.55, P=0.018, 95% CI 0.11,
      0.81). CONCLUSIONS: Serum cystatin C and serum creatinine show very similar
      correlations with creatinine and digoxin clearances. Serum cystatin C does not
      offer any advantages in this respect. It remains to be seen whether cystatin C
      offers any advantage over creatinine in elderly people in other respects.

PMID- 11966675
TI  - Syncope following oral chloroquine administration in a hypertensive patient
      controlled on amlodipine.

PMID- 11966676
TI  - Amlodipine and grapefruit juice.

PMID- 11966678
TI  - Beta-adrenoceptor blockers and serotonin.

PMID- 11966680
TI  - CYP2C9 polymorphism and warfarin dose requirements.

PMID- 11966681
TI  - CYP2C9 polymorphisms and CYP2C9*2 genotyping primers.

PMID- 11966683
TI  - Novel immune-based therapies for psoriasis.
AB  - The primacy of the immune system in the pathogenesis of psoriasis is a well
      established concept to the extent that psoriasis has been classified as a T-cell
      mediated, autoimmune disease. An explosion of knowledge concerning immunological
      events in psoriasis and the clinical efficacy of immunologically directed
      therapies, such as cyclosporin, support this concept. Armed with this
      understanding and modern biotechnology, novel interventions have been developed
      to treat psoriasis. The aim of these therapies is to provide selective,
      immunologically directed intervention with the hope that such specificity will
      result in fewer side-effects than traditional therapies. Of interest and
      importance, these pharmaceutical interventions also act as a form of
      investigational tool in psoriasis. Their relative efficacy in the psoriatic
      process provides useful insights into the hierarchial importance of immune events
      in the disease process and recent evidence suggests that innate rather than
      acquired immunity has a key role. This article reviews recent developments in
      immune-based therapies for psoriasis.

PMID- 11966684
TI  - Guidelines for topical photodynamic therapy: report of a workshop of the British
      Photodermatology Group.
AB  - Topical photodynamic therapy (PDT) is effective in the treatment of certain non
      melanoma skin cancers and is under evaluation in other dermatoses. Its
      development has been enhanced by a low rate of adverse events and good cosmesis.
      5-Aminolaevulinic acid (ALA) is the main agent used, converted within cells into
      the photosensitizer protoporphyrin IX, with surface illumination then triggering
      the photodynamic reaction. Despite the relative simplicity of the technique,
      accurate dosimetry in PDT is complicated by multiple variables in drug
      formulation, delivery and duration of application, in addition to light-specific
      parameters. Several non-coherent and coherent light sources are effective in PDT.
      Optimal disease-specific irradiance, wavelength and total dose characteristics
      have yet to be established, and are compounded by difficulties comparing light
      sources. The carcinogenic risk of ALA-PDT appears to be low. Current evidence
      indicates topical PDT to be effective in actinic keratoses on the face and scalp,
      Bowen's disease and superficial basal cell carcinomas (BCCs). PDT may prove
      advantageous where size, site or number of lesions limits the efficacy and/or
      acceptability of conventional therapies. Topical ALA-PDT alone is a relatively
      poor option for both nodular BCCs and squamous cell carcinomas. Experience of the
      modality in other skin diseases remains limited; areas where there is potential
      benefit include viral warts, acne, psoriasis and cutaneous T-cell lymphoma. A
      recent British Photodermatology Group workshop considered published evidence on
      topical PDT in order to establish guidelines to promote the efficacy and safety
      of this increasingly practised treatment modality.

PMID- 11966685
TI  - Cytotoxic effects of antimicrobial photodynamic therapy on keratinocytes in
      vitro.
AB  - BACKGROUND: Previous work has shown that cutaneous microbial species associated
      with skin conditions of microbial aetiology are susceptible to killing by
      photodynamic therapy (PDT) using visible light and methylene blue. Antimicrobial
      PDT (APDT) in vivo would require a therapeutic regimen where bacteria could be
      killed without damaging adjacent tissue. OBJECTIVES: To study keratinocyte
      killing in vitro using APDT. METHODS: We used a combination of methylene blue
      (100 microg mL(-1)) and visible light (42 mW cm(-2)), previously used for
      microbial killing, to study cytotoxic effects on keratinocytes. Kill rates and
      subsequent D-values were determined against a human keratinocyte cell line (H103)
      using trypan blue and neutral red dye viability tests. RESULTS: The kill rates
      for keratinocytes were exponential over the 90- and 180-min period of the
      experiment for neutral red and trypan blue, respectively. The corresponding D
      values were shown to be 198 and 205 min using trypan blue exclusion and neutral
      red uptake viability tests, respectively. CONCLUSIONS: The kill rates for
      keratinocytes were 18-200-fold slower than those previously determined for
      cutaneous microbial species, suggesting that in vivo, APDT sufficient to reduce
      microbes by seven log cycles would have little cytotoxic effect on keratinocytes.
      This approach may offer a safe alternative to conventional antimicrobial
      treatment.

PMID- 11966686
TI  - The novel tumour suppressor gene ING1 is overexpressed in human melanoma cell
      lines.
AB  - BACKGROUND: Epidemiological evidence indicates that exposure to ultraviolet (UV)
      radiation is directly linked to the increase of both incidence and mortality of
      melanoma. However, the genetic changes caused by UV radiation that lead to
      melanoma formation remain poorly understood. Recently, a potential tumour
      suppressor gene ING1 (inhibitor of growth 1) was shown to inhibit cell growth and
      induce apoptosis in the presence of p53. We have demonstrated that the expression
      of ING1 is induced after UV irradiation and that ING1 enhances the repair of UV
      damaged DNA. OBJECTIVES: To investigate if ING1 plays a role in melanoma
      formation. METHODS: We examined p33ING1 expression levels in 14 melanoma cell
      lines. RESULTS: We found that p33ING1 is overexpressed at both mRNA and protein
      levels in melanoma cell lines compared with normal melanocytes. Single-strand
      conformation polymorphism (SSCP) analysis showed band shifting in two melanoma
      cell lines. DNA sequencing confirmed that there were nucleotide alterations in
      the ING1 gene in Sk-mel-24 and Sk-mel-110 cell lines. Two silent nucleotide
      alterations in exon 1a were detected in Sk-mel-110. In Sk-mel-24, the A-->G
      nucleotide alteration at codon 260 resulted in an amino acid change from Asn to
      Ser, while seven other nucleotide alterations were silent. To determine if the
      silent nucleotide alterations in these two melanoma cell lines were due to
      polymorphism, SSCP analysis of ING1 gene was performed in 25 healthy volunteers.
      No band shift was observed in the SSCP analysis, suggesting that the nucleotide
      alterations in the melanoma cell lines are unlikely to be due to polymorphism.
      CONCLUSIONS: Taken together, our data demonstrate that ING1 is overexpressed, but
      infrequently mutated, in melanoma cell lines.

PMID- 11966687
TI  - Vascular endothelial growth factor causally contributes to the angiogenic
      response upon ultraviolet B irradiation in vivo.
AB  - BACKGROUND: Ultraviolet (UV)-B irradiation has been shown to be an inducer of
      vascular endothelial growth factor (VEGF) in primary keratinocytes and epidermal
      cell lines in vitro. OBJECTIVES: To determine the expression pattern and the
      causal role of VEGF in the UVB-mediated angiogenic response in vivo in human skin
      and in a mouse model. METHODS: Skin biopsies or epidermal lysates thereof were
      studied for VEGF expression following UVB irradiation at a dose of 50 or 60 mJ cm
      2, respectively, using immunostaining and a VEGF-specific highly sensitive
      sandwich enzyme-linked immunosorbent assay. The VEGF-dependent increase in
      vessels upon repetitive UVB irradiation was studied in skh-1 hairless mice using
      immunostaining for factor VIII-related antigen (FVIII RAG) in the presence and
      absence of intraperitoneally injected neutralizing VEGF antibodies. RESULTS: VEGF
      was found to be induced in the epidermis following UVB irradiation of human and
      mouse skin. Repetitive UVB irradiation of skh-1 hairless mice resulted in an
      increase in FVIII RAG positive vessels in the skin. UVB-induced angiogenic
      response could be partly abrogated by neutralizing antibodies against VEGF, while
      isotype-matched IgG control antibodies did not reveal any suppressive effect.
      CONCLUSIONS: Our results support previous in vitro data and show the in vivo
      relevance of VEGF as a paracrine inducer of cutaneous vessels after UVB
      irradiation.

PMID- 11966688
TI  - Smoking affects collagen synthesis and extracellular matrix turnover in human
      skin.
AB  - BACKGROUND: Smoking is associated with premature facial wrinkling and aberrant
      wound healing, but the underlying mechanisms of skin injury are poorly
      understood. OBJECTIVES: To compare the in vivo collagen synthesis and degradation
      in the skin of smokers and non-smokers. METHODS: The study population consisted
      of 47 current smokers and 51 individuals who had never smoked from northern
      Finland. Suction blisters were induced in the sun-protected upper inner arm of
      the study subjects, after which suction blister fluid (SBF) was collected for
      analyses of the levels of aminoterminal procollagen propeptides of type I and III
      collagens (PINP and PIIINP, respectively), matrix metalloproteinase (MMP)-8 and
      tissue inhibitor of MMP (TIMP)-1. PINP, PIIINP and TIMP-1 were also determined
      from serum samples. The levels of active and pro MMP-1 were assessed from deep
      frozen skin biopsies by Western blotting. RESULTS: The synthesis rates of type I
      and III collagens were lower by 18% and 22%, respectively, in the SBF of the
      smokers compared with the non-smokers. The levels of MMP-8 were higher by 100% in
      the SBF of the smokers. The levels of MMP-1 in the skin biopsies did not differ
      significantly between the groups. The levels of TIMP-1 in SBF were 14% lower in
      the smokers than in the non-smokers, whereas the serum concentrations of TIMP-1
      did not differ between the groups. CONCLUSIONS: Smoking decreases the synthesis
      rates of type I and III collagens in skin in vivo and alters the balance of
      extracellular matrix turnover in skin.

PMID- 11966689
TI  - Mutation analysis of ATP2C1 gene in Taiwanese patients with Hailey-Hailey
      disease.
AB  - BACKGROUND: Hailey-Hailey disease (HHD) is an autosomal dominant disorder with
      recurrent eruption of vesicles and bullae involving predominantly the neck, groin
      and axillary regions. Histopathology shows suprabasal cleavage in epidermal
      cells. Recent studies have revealed that HHD is caused by mutations in the ATP2C1
      gene encoding a novel Ca2+ pump. OBJECTIVES: To analyse the mutations of the
      ATP2C1 gene in Taiwanese patients with HHD. METHODS: In total, five familial and
      two sporadic cases of HHD were retrieved from the medical records. The diagnosis
      of HHD was made based on the characteristic clinical features and
      histopathological evidence. All 27 exons and flanking intron boundaries were
      amplified by polymerase chain reaction and products analysed by direct
      sequencing. RESULTS: We identified six novel mutations and one reported mutation:
      three deletion mutations (nt884-904del, 1459delCTCA, 1975delA), two non-sense
      mutations (R39X, R783X), one mis-sense mutation (A730T) and one splicing mutation
      (483 + 2T-->A). The non-sense mutation R39X had been reported previously; the
      other six mutations are novel mutations. CONCLUSIONS: These results demonstrate
      that a spectrum of ATP2C1 gene mutations is present in Taiwanese HHD patients.

PMID- 11966690
TI  - The hairless gene in androgenetic alopecia: results of a systematic mutation
      screening and a family-based association approach.
AB  - BACKGROUND: Genetic disposition and androgen dependence are important
      characteristics of the common patterned loss of scalp hair known as androgenetic
      alopecia (AGA). The genetic factors contributing to AGA are currently unknown.
      The human hairless gene (HR) has recently been cloned and mutations have been
      reported in families with autosomal recessive universal congenital alopecia and
      papular atrichia. The main feature of these disorders is persistent complete
      absence of hair at or shortly after birth. This suggests that HR is essential and
      specific for the development of hair. OBJECTIVES: To test the hypothesis that HR
      may be involved in AGA. METHODS: We systematically screened HR for genetic
      variability by means of single-strand conformation analysis (SSCA) in 46
      unrelated men with AGA. To test for an involvement of HR in the development of
      AGA, seven common variants were genotyped in 61 families with 93 affected
      offspring. The results were analysed with the transmission/disequilibrium test
      (TDT). RESULTS: SSCA showed 15 single nucleotide substitutions: eight missense
      mutations, four silent mutations and three mutations in exon-flanking intronic
      sequences. TDT results showed a marginally significant association between AGA
      and variants 3379-29G/T (P = 0.024) and 2611-68C/T (P = 0.047). These results,
      however, did not remain significant after applying the conservative Bonferroni
      correction for multiple testing. CONCLUSIONS: Our results do not provide evidence
      for a strong involvement of HR in the development of AGA, although a minor role
      cannot be fully excluded.

PMID- 11966691
TI  - An immunohistochemical study of abnormal keratinocyte proliferation in molluscum
      contagiosum.
AB  - BACKGROUND: Molluscum contagiosum is a common cutaneous tumour that is
      characterized by usually spontaneous involution and self-limited spreading in
      immunocompetent individuals. OBJECTIVE: We aimed to investigate the apoptosis and
      the expression of cell-cycle proteins in molluscum contagiosum lesions. METHODS:
      The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick
      end labelling (TUNEL)-based apoptotic index and the expression of the cell-cycle
      proteins Ki-67, p53, p21WAF and Bcl-2 were investigated in molluscum contagiosum
      lesions obtained from the trunk of 20 immunocompetent patients and in normal skin
      samples from the trunk of six healthy volunteers. RESULTS: Whereas molluscum
      contagiosum lesions displayed a TUNEL-based apoptotic index similar to that of
      normal skin, they exhibited an increased Ki-67 index, which was confined to the
      basal and first suprabasal layers (P < 0.001). Compared with normal non-sun
      exposed skin, molluscum contagiosum lesions also exhibited increased p53 staining
      in basal cells (P < 0.01), increased p21WAF in suprabasal cells (P < 0.001) and
      loss of Bcl-2 expression. CONCLUSIONS: These results indicate that molluscum
      contagiosum lesions exhibit an increased proliferation rate of keratinocytes,
      which is likely to be partially counteracted by accumulation of p53.

PMID- 11966692
TI  - An audit of the use of self-administered adrenaline syringes in patients with
      angio-oedema.
AB  - BACKGROUND: Self-administered adrenaline syringes may be prescribed for patients
      at risk of life-threatening episodes of angio-oedema or anaphylaxis. OBJECTIVES:
      To determine whether patients are able to use these syringes appropriately and
      adequately. METHODS: Twenty-nine consecutive patients who had been prescribed
      self-administered adrenaline syringes for severe angio-oedema were recruited. All
      completed a questionnaire (unsupervised), and were asked to demonstrate how to
      use a dummy syringe. RESULTS: Three of 29 (10%) patients had been prescribed
      syringes in the absence of severe angio-oedema or collapse. Seventeen of 29 (59%)
      patients had been prescribed two syringes, and 21 of 29 (72%) kept a syringe with
      them at all times. Twenty of 28 (71%) patients had had the use of a syringe
      demonstrated to them with the initial prescription, but two of 29 (7%) had never
      been shown how to use it. Only six of 26 (23%) patients had been told to
      telephone for an ambulance after using a syringe. Only seven of 29 (24%) patients
      would use a syringe for an episode of collapse, whereas eight of 28 (29%) would
      use one for an episode of lip swelling. Nine of 21 (43%) patients had not been
      warned about adverse effects, although 13 of 20 (65%) given adrenaline had had at
      least one adverse effect. Of the 25 patients asked to demonstrate their use of a
      syringe, only 14 (56%) were able to perform all steps correctly, and three (12%)
      were unable to perform any of the steps. Despite this, all 29 patients felt
      confident about giving themselves an injection, and most felt more secure having
      been prescribed syringes. CONCLUSIONS: As self-administered adrenaline syringes
      are prescribed for life-threatening events, it is vital that they are given to
      appropriate patients with adequate written instructions and proper demonstration
      at the time of the initial prescription. As a result of this study we have
      developed a more detailed patient information leaflet, and all patients are shown
      how to use a syringe for a second time when attending the clinic for follow-up.

PMID- 11966693
TI  - Combining lesional short-contact dithranol therapy of psoriasis with a potent
      topical corticosteroid.
AB  - BACKGROUND: Since its introduction, the effectiveness of dithranol in treating
      psoriasis has been unequalled by other topical treatments. Out-patient short
      contact dithranol treatment is effective with regard to clinical response rate
      and relapse rate after 1 year. A drawback, however, is the relatively long
      treatment duration. OBJECTIVES: To study a dithranol regimen combined with a
      potent topical corticosteroid with regard to clinical response rate, treatment
      duration and remission period after clearance. METHODS: Twelve patients with
      stable psoriasis vulgaris participated in this study. We treated three comparable
      psoriasis lesions on the extremities for 39 consecutive days. The first lesion
      was treated daily with short-contact dithranol cream followed by clobetasol-17
      propionate ointment 5 days per week. The second lesion was treated daily with
      short-contact dithranol cream followed by the vehicle of clobetasol-17-propionate
      ointment. The third lesion was treated with clobetasol-17-propionate ointment 5
      days per week. The patients attended on days 1, 4, 9, 12, 15, 18, 22, 25, 32 and
      39 during treatment. We assessed lesional severity scores at each visit and
      registered the baseline area at the first visit. During the follow up at weeks 2,
      4, 6, 10, 14, 19 and 23 we assessed lesional sum scores. We also estimated the
      area involved in recurrence of the lesion as a percentage of the baseline area.
      The overall differences between the three treatment curves for the treatment
      period and follow-up period separately were tested with a likelihood ratio test.
      RESULTS: Differences between the curves of the sum scores during treatment (P <
      0.001) were mainly due to the different time-course of dithranol monotherapy,
      which showed a slower decrease in sum score. Differences between the linear
      trends of the sum score (P < 0.001) and the area score P < 0.001) during follow
      up were due to a different time-course of the combination therapy, which started
      lower and increased more slowly, suggesting a slower relapse rate with
      combination therapy. When comparing the follow-up data, it must be kept in mind
      that the three treatments showed an overall significantly different sum and area
      score at the start of follow up. CONCLUSIONS: Intermittent addition of clobetasol
      17-propionate ointment enhanced the antipsoriatic efficacy of short-contact, high
      dose dithranol therapy in terms of clearing capacity and treatment duration,
      without shortening remission duration.

PMID- 11966694
TI  - Eczema: quality of life by body site and the effect of patch testing.
AB  - BACKGROUND: Patients with dermatitis are known to have impaired quality of life.
      Whether this varies according to body site has not been evaluated. Patch tests
      have previously been shown to influence quality of life, although no previous
      studies have shown if this is dependent on the results of the patch tests.
      OBJECTIVES: To evaluate the impact of patch testing on quality of life according
      to the outcome of the investigations and to determine how quality of life varies
      according to eczema body site. METHODS: One hundred and sixty consecutive adult
      patients with active eczema were selected from a patch test clinic for inclusion
      into the study. Quality of life was determined using the Dermatology Life Quality
      Index (DLQI) and the SF-36, prior to patch testing and 2 months later. Perceived
      eczema severity at each time point was also noted, along with the outcome of
      patch testing. Baseline comparison of quality of life was performed between four
      body site groups (face, hand, generalized, other). RESULTS: Patients confirmed as
      having relevant positive contact allergens were shown to have a significant
      improvement in both perceived eczema severity (P = 0.0004) and DLQI score (P =
      0.0015) at 2 months after patch testing. No significant changes were noted in the
      SF-36 score, other than a borderline improvement in the pain score (P = 0.048).
      The improvement in quality of life and eczema severity was not noted in patients
      with negative patch tests. Eighty-nine per cent of patients diagnosed as having
      contact allergy were able to comply with avoidance advice. No significant
      variation was noted in quality of life according to body site affected by eczema.
      There was a positive correlation between DLQI score and perceived eczema severity
      (P < 0.0001). CONCLUSIONS: Patients confirmed as having contact allergy show a
      subsequent improvement in eczema severity and an improvement in quality of life.

PMID- 11966695
TI  - Rarity of hypertension in adult patients with atopic dermatitis.
AB  - BACKGROUND: Patients with atopic dermatitis show a tendency for vasoconstriction
      of the small vessels in the skin. As peripheral vasoconstriction contributes to
      the cause of hypertension, it is natural to suppose that blood pressures might be
      on the high side in adult patients with atopic dermatitis. In the literature,
      however, there was little information on the subject. OBJECTIVES: To study the
      incidence of hypertension in adult patients with atopic dermatitis.
      PATIENTS/METHODS: Blood pressure was measured in 521 adult patients with active
      atopic dermatitis (235 males; 286 females) aged 30-59 years, and 87 adults with
      "healed" atopic dermatitis (26 males; 61 females) aged 34-52 years. The blood
      pressures were classified as definite hypertension, borderline hypertension or
      normal blood pressure. RESULTS: In those patients aged 30-39 years with active
      atopic dermatitis, the incidence of definite hypertension in the male patients
      and the female patients was 1.1% and 1.6%, respectively. The incidence remained
      almost at a plateau for the 30-39-year-old age group through to the 50-59-year
      old age group, in both the male and female patients. There was no difference in
      the incidence of definite hypertension between patients with severe dermatitis
      and patients with mild dermatitis. Adult patients with "healed" atopic dermatitis
      also showed a low incidence of definite hypertension. CONCLUSIONS: These findings
      indicate that hypertension is rare in adult patients with atopic dermatitis. It
      is most probable that the rarity of hypertension is a primary feature of the
      disease.

PMID- 11966696
TI  - Decrease in nickel sensitization in a Danish schoolgirl population with ears
      pierced after implementation of a nickel-exposure regulation.
AB  - BACKGROUND: To reduce the skin nickel exposure of the population, the Danish
      Ministry of Environment issued a regulation that was implemented in 1992, and the
      European Union countries have recently adopted an expanded regulation.
      OBJECTIVES: The aim of our combined patch testing and questionnaire investigation
      of girls in public schools and high schools/production schools was to evaluate
      whether the regulation has had an impact on the prevalence of nickel
      sensitization. METHODS: To find a group of girls with ears pierced mainly after
      implementation of the nickel-exposure regulation in Denmark, girls were recruited
      from the fifth and sixth grade in 12 public schools (the public school group).
      After the public school level almost all girls from a public school population
      continue their education in high schools or other schools such as production
      schools or technical schools. Therefore, to find girls demographically similar to
      the public school girls but older, and with ears pierced before implementation of
      the regulation, girls from seven high schools and two production schools were
      recruited (the high school group). Four hundred and twenty-seven girls in the
      public school group (mean age 12.4 years, range 10-14) and 534 in the high school
      group (mean age 18.8 years, range 17-22) participated. All participants filled
      out a questionnaire concerning ear piercing, use of oral braces and former patch
      testing for nickel sensitivity. Three hundred and five girls (71.4%) in the
      public school group and 275 (51.5%) in the high school group were patch tested or
      had been tested previously and the results of these tests were included in the
      study. The relation between the frequency of nickel sensitization and the various
      factors that might influence the prevalence of nickel sensitization was evaluated
      by multivariate logistic regression analysis. The investigation was conducted
      from March 1999 to March 2000. RESULTS: The study showed that both increasing age
      and having ears pierced before 1992 enhanced the prevalence of nickel
      sensitization. We found that 17.1% of the girls in the high school group
      demonstrated a positive patch test reaction to nickel. In contrast, the
      prevalence of nickel sensitization in the public school group was only 3.9%.
      Comparing girls with and without pierced ears, the prevalence of nickel
      sensitization was significantly higher in girls with ears pierced before, but not
      after, 1992 (odds ratio 3.34 and 1.20, respectively). Only in the high school
      group was there a tendency that wearing oral braces before ear piercing had a
      protective effect on nickel sensitization, but this did not reach statistical
      significance. CONCLUSIONS: As we found an effect of ear piercing before but not
      after 1992, this study strongly suggests that implementation of the nickel
      exposure regulation in 1992 in Denmark has had the intended effect of protecting
      the female population from becoming allergic to nickel.

PMID- 11966697
TI  - Cutaneous adverse reactions to clindamycin: results of skin tests and oral
      exposure.
AB  - BACKGROUND: Clindamycin is an antibiotic used in anaerobic and severe complicated
      infections. It is often selected for patients with a history of allergy to other
      antibiotics. OBJECTIVES: To study the occurrence of clindamycin hypersensitivity
      and to determine whether skin tests are useful in cases of suspected clindamycin
      allergy. METHODS: Six patients with an exanthematous rash and a history strongly
      suggestive of clindamycin hypersensitivity were studied with skin tests and oral
      exposure. Cases of suspected adverse drug reactions to clindamycin reported to
      the National Register of Adverse Effects of Drugs (NRAED) in Finland during 1973
      2000 were analysed. RESULTS: In the skin tests true-positive patch test reactions
      were seen in four of six patients, while 22 healthy control patients were
      negative. One false-positive and one false-negative patch test reaction were
      seen. During 1973-2000, 29 suspected cases of skin and/or mucosal membranes
      affected by clindamycin were reported to the NRAED. CONCLUSIONS: Clindamycin
      hypersensitivity is not common. Delayed-type allergic reactions occur and patch
      tests are useful in those cases. Oral exposure is the method of choice if
      possible, as false-negative and false-positive reactions may occur.

PMID- 11966698
TI  - Free radicals in antigen formation: reduction of contact allergic response to
      hydroperoxides by epidermal treatment with antioxidants.
AB  - BACKGROUND: For patients with allergic contact dermatitis, the main therapy is
      anti-inflammatory steroids, a non-specific and symptomatic treatment. In contact
      allergy, the antigen formation is considered to be the binding of a chemical
      (hapten) to a biological macromolecule, e.g. a protein. Limonene-2-hydroperoxide
      (Lim-OOH) is a hapten with a known allergenic effect. It is likely to bind to
      proteins in the skin via a radical mechanism. It might be possible to inhibit the
      allergic reaction by epidermal application of substances that can trap free
      radicals, e.g. antioxidants such as ascorbic acid or alpha-tocopherol, prior to
      the application of the hapten. OBJECTIVES: To study the influence of antioxidants
      on the allergenic effect of Lim-OOH in sensitization experiments on guinea pigs.
      METHODS: Pretreatment with the antioxidants was performed before induction to
      study the effect on sensitization as well as before challenge testing to study
      the effect on elicitation. RESULTS: A reduction in the response rate was found
      both at sensitization and at elicitation. The antioxidants had no effect on
      cobalt allergy or on the allergenic effect of haptens that form antigens via
      nucleophilic-electrophilic reactions. No reduction of the effect was seen for
      irritants. CONCLUSIONS: The protective effect of antioxidants in elicitation
      could be of practical therapeutic value, as it indicates a possibility for the
      treatment of patients who have become sensitized to haptens that form full
      antigens via a radical mechanism.

PMID- 11966699
TI  - Arrector pili muscle: evidence of proximal attachment variant in terminal
      follicles of the scalp.
AB  - BACKGROUND: There is general agreement that the proximal attachment site of the
      arrector pili (AP) muscle, via elastic tendons, is the bulge region, where
      follicular stem cells are situated. A variant of this insertion, in which the AP
      muscle surrounds the follicle circumference, has been described in human facial
      vellus hair follicles. OBJECTIVES: To investigate whether terminal hair follicles
      of the human scalp may also present this variant of proximal insertion of the AP
      muscle. METHODS: Histological and immunohistochemical methods were used. RESULTS:
      At the bulge level, bundles of the AP muscle were seen to encircle the entire
      hair follicle. CONCLUSIONS: Terminal follicles of the human scalp may also
      present this variant of proximal insertion of the AP muscle.

PMID- 11966700
TI  - Is daily use of sunscreens of benefit in the U.K.?
AB  - BACKGROUND: There is an increasingly widespread belief that year-round use of
      topical agents containing ultraviolet (UV)-absorbing ingredients is an important
      factor in reducing the chronic degenerative cutaneous changes associated with sun
      exposure. OBJECTIVES: To evaluate the benefit of using sunscreens during
      different periods of the year for people living in the U.K. METHODS: An analysis
      was made of typical solar UV exposure at different times of the year in relation
      to different topical sunscreen practices. RESULTS: It was shown that using sun
      protection products during the six summer months (April-September) can reduce the
      lifetime (70 years) UV exposure of a person by an equivalent of almost 40 years
      unprotected exposure. However, virtually no benefit is gained from using UV
      protective products from October to March in the U.K. CONCLUSIONS; As their use
      is not without cost and the risk of adverse effects, topical products containing
      UV filters are best avoided during October to March in the U.K.

PMID- 11966701
TI  - Primary subcutaneous follicular centre cell lymphoma with involvement of the
      galea: a case report and short review of the literature.
AB  - Primary cutaneous follicular centre cell lymphoma (FCCL) is a distinct subtype of
      cutaneous lymphoma that originates from germinal centre cells. Histologically,
      the disease is typified by a bottom-heavy infiltrate with a diffuse or follicular
      growth pattern situated in the mid or deep dermis. In some cases, the neoplastic
      infiltrate may involve the underlying subcutaneous tissue, but so far primary
      subcutaneous FCCL has not been reported. We report the first case of primary FCCL
      located primarily in the deep subcutis with extension into the galea and review
      the literature on primary subcutaneous B-cell lymphomas.

PMID- 11966702
TI  - Treatment of disseminated granuloma annulare with a 5-lipoxygenase inhibitor and
      vitamin E.
AB  - Histologically, granuloma annulare (GA) is a common non-infectious necrobiotic
      granulomatous reaction pattern that correlates with a number of different, but
      relatively specific clinical presentations. The cause or causes of GA are
      unknown: when localized, it is usually self-limiting, but it may be persistent
      when disseminated. We present three women who had had disseminated GA for more
      than 1 year. One patient had previously been treated with isotretinoin with no
      response. All three patients were treated with vitamin E 400 IU daily and
      zileuton 2400 mg daily. All responded within 3 months with complete clinical
      clearing. The anti-inflammatory and immune regulatory effects of vitamin E and
      zileuton may be an effective treatment in some patients with prolonged
      disseminated/generalized GA.

PMID- 11966703
TI  - Merkel cell carcinoma in a black human immunodeficiency virus-infected patient.
AB  - Merkel cell carcinoma (MCC) is a rare malignant tumour that develops in sun
      exposed areas in immunocompromised patients (chronic lymphocytic leukaemia,
      transplant recipients) older than 50 years. We report MCC in a young black woman
      with human immunodeficiency virus (HIV) infection. A 2-cm binodular violaceous
      lesion developed on her left ear lobe. Extensive work-up, including computed
      tomographic scans of the neck, chest, abdomen and pelvis, octreotide scan and
      sentinel node biopsy, did not demonstrate any metastasis. A wide excision was
      performed and the patient remained free of disease after 9 months. This case is
      the fourth observation of MCC in an HIV-infected patient.

PMID- 11966704
TI  - Cutaneous lymphatic amyloid deposits in "Hungarian-type" familial transthyretin
      amyloidosis: a case report.
AB  - Multiple transthyretin (TTR) mutations have recently been identified and
      implicated in the development of familial systemic amyloidoses, but early
      diagnosis of these disorders is still largely unresolved. We investigated the
      presence and tissue distribution of TTR-derived amyloid in skin biopsies of a 59
      year-old woman carrying the "Hungarian-type" mutation of TTR (Asp18Gly). Clinical
      symptoms involved severe central nervous system dysfunction without signs of
      polyneuropathy, also referred to as the "central form" of TTR-related systemic
      amyloidosis. Skin biopsy was also evaluated as a tool in order to diagnose this
      type of TTR amyloidosis. Biopsy samples were collected from the infra-axillary
      region. Light microscopy using Congo red and polarized light was used to diagnose
      amyloid deposits. Subsequently, electron microscopic analysis was performed to
      correlate the amyloid deposits with vicinal dermal structures. The amyloid class
      was determined by means of immunocytochemistry. TTR amyloid was primarily
      localized to lymphatic microvessels in the present case, whereas arterioles were
      devoid of TTR amyloid deposits. In addition, the well-known association of TTR
      amyloid with neural structures along the erector pilorum and around the sebaceous
      and serosal (sweat) glands was also evident. Electron microscopic analysis of
      amyloid deposits revealed characteristic amyloid fibrils that were irregular in
      shape, and exhibited a heterogeneous density and a random deposition pattern.
      Immunocytochemistry confirmed the cutaneous accumulation of TTR amyloid. In
      conclusion, amyloid deposits were abundantly present in the skin of a patient
      with "Hungarian-type" TTR amyloidosis; skin biopsy seems to be appropriate for
      the diagnosis of this disorder. We showed that besides the erector pilorum, sweat
      glands and nerve terminals, lymphatic microvessels are also severely infiltrated
      by TTR amyloid. Whether these pathological alterations can exclusively be found
      in "Hungarian-type" TTR amyloidosis should still be investigated. If such changes
      are not specific for the Asp18Gly mutation, they may be considered as diagnostic
      markers for "central" TTR amyloid disorders.

PMID- 11966705
TI  - Palmoplantar keratoderma and oral leucoplakia with cutaneous horn of the lips.
AB  - The inherited palmoplantar keratodermas (PPK) may be associated with a wide
      variety of other ectodermal abnormalities. The coexistence of PPK and leucoplakia
      may indicate the increased risk of oesophageal carcinoma in adult life. Cutaneous
      horn may develop over benign, precancerous, as well as malignant lesions, and
      frequently may be associated with actinic keratoses and Bowen's disease. On the
      other hand, the relationship of cutaneous horn and leucoplakia has been the
      subject of only a single case report. We present a case of PPK and diffuse oral
      leucokeratosis associated with relapsing cutaneous horn of the lips.

PMID- 11966707
TI  - Cutaneous protothecosis: report of five cases.
AB  - Prototheca, a genus of achlorophyllic algae, is a rare cause of opportunistic
      infection in humans. About 80 human cases, mostly cutaneous infection caused by
      P. wickerhamii, have been reported world-wide. We describe the
      clinicopathological findings and treatments of five cases diagnosed in our
      department during the period 1991-97. The patients, including four elderly
      farmers, presented with pyoderma-like lesions or infiltrating papules and plaques
      on the extensor side of the extremities or face. All patients were
      immunocompromised, mostly due to systemic or topical steroids. The diagnosis was
      made in each case by finding typical endospores with morula-like structures in
      skin biopsy specimens. P. wickerhamii was isolated in four cases in which
      pretreatment culture of skin tissue was done. Except for one patient who died of
      asthma, the infection was cured after 2-7 weeks of amphotericin B, ketoconazole,
      itraconazole or fluconazole. Our cases illustrate that cutaneous protothecosis
      commonly manifested non-tender, pyoderma-like or infiltrating lesions and should
      be considered in the differential diagnosis of deep fungal or mycobacterial
      infection. This rare infection seemed more frequent in our region, possibly due
      in part to common steroid abuse among old people in Taiwan and there was a large
      population of elderly farmers in our area.

PMID- 11966706
TI  - The transition of pemphigus vulgaris into pemphigus foliaceus: a reflection of
      changing desmoglein 1 and 3 autoantibody levels in pemphigus vulgaris.
AB  - The transition of pemphigus vulgaris (PV) into pemphigus foliaceus (PF) is rare
      and the immunological changes underlying this event are not well understood. We
      report a 44-year-old woman who presented with oral and cutaneous erosions typical
      of PV. Over a 9-year period, the clinical features evolved into those of PF. To
      examine whether quantitative changes in desmoglein (Dsg) antibodies were
      associated with this transition, Dsg1 and Dsg3 antibody levels were measured by
      enzyme-linked immunosorbent assay in 82 sequential serum samples collected over
      this period. At presentation, when the phenotype was PV with oral and cutaneous
      erosions, antibodies to both Dsg1 and Dsg3 were detected. The disappearance of
      oral involvement was associated with a decline in Dsg3 antibodies, which are now
      undetectable, while the development of more severe skin involvement was
      associated with rising Dsg1 antibody levels. These data strongly suggest that the
      change in clinical features is a reflection of qualitative and quantitative
      changes in antibody profile. It is not known whether the transition to PF is
      permanent or whether disease relapses in the future may be associated with the re
      emergence of Dsg3 antibodies, oral ulceration and a PV phenotype.

PMID- 11966708
TI  - Cutaneous polyarteritis nodosa.
AB  - Classic polyarteritis nodosa (PAN) is a segmentary leucocytoclastic vasculitis
      that affects small- and medium-sized arteries. In 1931, Lindberg (Acta Med Scand
      1931; 76: 183-225) described the existence of a cutaneous variant of PAN, without
      visceral involvement and with a more favourable prognosis. We present four
      patients diagnosed with cutaneous PAN in our hospital between 1987 and 1998. The
      study group was composed of three women and one child, whose ages ranged from 11
      to 70 years old. The follow-up period was between 2 and 13 years. Each patient
      was submitted for an initial clinical, histological and laboratory evaluation and
      subsequent follow-up. The presence of nodules was the most frequent cutaneous
      lesion, preferentially located in the lower limbs. The erythrocyte sedimentation
      rate was the only parameter that was altered in all patients. Cutaneous biopsies
      from all patients showed a segmentary leucocytoclastic vasculitis in the arteries
      of the deep dermis and/or hypodermis. Direct immunofluorescence was positive in
      just one patient. No visceral involvement was found in any patient. There is
      confusion about the correct definition of cutaneous PAN. Some clinical findings,
      such as nodules or livedo reticularis, typical of cutaneous PAN suggest a good
      prognosis; however, we consider that it is necessary to evaluate these patients
      for systemic involvement for the possibility of arteritis in other organs as the
      term polyarteritis suggests.

PMID- 11966709
TI  - Epstein-Barr virus-positive blastoid nasal T/natural killer-cell lymphoma in a
      caucasian.
AB  - T/natural killer (NK)-cell lymphoma is a subtype of non-Hodgkin's lymphoma, with
      frequent cutaneous involvement; it follows an aggressive course. Most cases are
      reported in Asia, and typically present with nasopharyngeal involvement. There is
      a distinct variant known as blastoid T/NK-cell lymphoma, which affects elderly,
      non-Asian patients, with absence of nasal involvement. We report a middle-aged
      caucasian man who had blastoid T/NK-cell lymphoma with nasal involvement.

PMID- 11966710
TI  - Parenteral vitamin D(3) and oral terbinafine for refractory chromoblastomycosis.

PMID- 11966711
TI  - Topical immunotherapy with contact sensitizers for viral warts.

PMID- 11966712
TI  - Maintenance psoralen plus ultraviolet A therapy: does it have a role in the
      treatment of severe atopic eczema?

PMID- 11966713
TI  - Antitumour necrosis factor-alpha antibodies (infliximab) in the treatment of a
      patient with toxic epidermal necrolysis.

PMID- 11966714
TI  - Nail changes due to docetaxel.

PMID- 11966715
TI  - Expression of peroxiredoxin and thioredoxin in dermatological disorders.

PMID- 11966716
TI  - Fibulin-2 and its association with fibrillin-rich microfibrils in the papillary
      dermis of photoaged skin.

PMID- 11966717
TI  - Intralesional triamcinolone for chondrodermatitis nodularis: a follow-up study of
      60 patients.

PMID- 11966718
TI  - Cutaneous protothecosis in an AIDS patient.

PMID- 11966724
TI  - The epidemiology of skin cancer.
AB  - Melanoma and non-melanoma (basal and squamous cell carcinoma) skin cancer (NMSC)
      are now the most common types of cancer in the white populations and the
      incidence of skin cancer has reached epidemic proportions. According to recent
      population-based studies from Australia the incidence rate is over 2% for basal
      cell carcinoma in males and 1% for squamous cell carcinoma, and there are over 50
      new cases of melanoma per 100 000.

PMID- 11966725
TI  - Photoprotective properties of skin melanin.
AB  - Melanins are a ubiquitous class of biological pigments, which play an important
      role in the photoprotection of skin. Recent advances in the chemistry of melanins
      have demonstrated their diversity. The various types of melanin show different
      physico-chemical properties, suggesting that their photobiological properties are
      not unique. In this review, the implications of melanin diversity for the natural
      photoprotection of skin are discussed.

PMID- 11966726
TI  - Photobiology and genetics of malignant melanoma.
AB  - The current state of knowledge of melanoma genetics is reviewed. Mutations in the
      tumour suppressor gene CDKN2A and in the oncogenes N-ras and H-ras seem to play
      the most important roles in the development and progression of malignant
      melanoma. Experimental studies to determine the role of ultraviolet (UV) light in
      the induction of melanoma have been hampered by a lack of suitable animal models.
      The commonly used laboratory animals are not susceptible to the induction of
      melanoma upon exposure to UV radiation (UVR) alone. Recent observations with four
      different animals have suggested, however, that UVR may be involved in the
      induction of melanoma. The most recent model consists of human skin grafted onto
      immunodeficient mice. To date, using this model, only the combination of UVB (280
      320 nm) exposure and topical promoter treatment has led to the development of
      malignant melanoma. The wavelength dependency of the induction of melanoma has
      been established in the fish model Xiphophorus. The application of such an action
      spectrum to humans looks possible.

PMID- 11966727
TI  - Carcinogenesis of basal cell carcinomas: genetics and molecular mechanisms.
AB  - Basal cell carcinoma (BCC) of the skin is the most common type of cancer in
      humans. Like squamous cell carcinomas, they are also believed to be ultraviolet
      (UV)-induced, but several data suggest that some differences might exist in the
      mechanisms of their UV induction. The originating cells may arise from
      interfollicular basal cells, hair follicles or sebaceous glands, thus from a
      deeper zone than the SCC ones, which probably means exposure to different doses
      or wavelengths of UV. The p53 gene and the patched gene (PTCH) are major targets
      of UV for BCC induction. Mutations in p53 are present in about 56% of human BCC,
      even small early lesions. The "UV signature" is observed in 65% of them.
      Mutations in the PTCH play also a major role in BCC development, being
      responsible for hereditary BCCs in Gorlin's syndrome, sporadic BCC, and BCCs
      isolated from xeroderma pigmentosum, although with a lower incidence of "UV
      signature". Smoothened-activating mutations and PTCH2 mutations are also involved
      in BCC formation. Transgenic mice overexpressing Smoothened or Sonic hedgehog in
      the skin spontaneously produce skin lesions resembling human BCCs, but contrary
      to findings in the hairless albino mouse and with SCC, no data on experimental UV
      induction of BCCs are available.

PMID- 11966728
TI  - From actinic keratosis to squamous cell carcinoma.
AB  - The development of actinic keratosis (AK) and squamous cell carcinoma (SCC) is
      the result of a complex sequence of events initiated by exposure to ultraviolet
      (UV) light. The application of sunscreens prior to sun exposure has been reported
      to reduce the incidence of AK. The initial damage takes place in the DNA and most
      of the UV-induced lesions in the DNA are repaired. However, mutations may occur
      as a result of base mispairing of the cell and its DNA replicate before the DNA
      lesion is repaired. The genes involved in the repair process are also potential
      UV targets. Mutations in the tumour suppressor gene p53 are a common feature of
      AK and SCC. The hairless mouse is the best available animal model, in which
      lesions resembling human AK (papillomas), keratoacanthomas and SCCs may be
      induced. This model of multistage carcinogenesis offers an excellent tool for
      mechanistic studies. The relative efficacy of UV wavelengths (action spectrum)
      that induce SCC has been determined using the hairless mouse as a model. The
      action spectrum has been extrapolated to humans skin and is recognised worldwide.

PMID- 11966729
TI  - Cutaneous malignant melanoma, sun exposure, and sunscreen use: epidemiological
      evidence.
AB  - BACKGROUND: Cutaneous malignant melanoma is the most serious form of skin cancer
      and accounts for about three-quarters of all skin cancer deaths. Over the last
      few decades the incidence and mortality rates of melanoma have been increasing
      worldwide. The risk of melanoma is higher in individuals with both phenotypic
      susceptibility and a history of sun exposure. Therefore, recommended sun
      protection behaviours include wearing long-sleeved clothing, seeking shade,
      avoiding the sun when it is strongest, and using sunscreen lotion with a sun
      protection factor of 15 or higher. It has been reported, however, that the use of
      sunscreens does not protect against melanoma and seems to increase the duration
      of recreational sun exposure. METHODS: Published epidemiological studies
      examining sunscreen use and melanoma have been reviewed from an epidemiological
      point of view, taking into account potential biases. We have classified case
      control studies into four categories: (1) inconclusive studies because of major
      bias in control population and/or the lack of multivariate analysis; (2) no
      association between sunscreen use and melanoma after controlling for confounders;
      (3) negative association (i.e. protective effect of sunscreen); and (4) positive
      association. Various other epidemiological studies were also analysed. RESULTS:
      These results are controversial. Two case-control studies show a protective
      effect of sunscreen use, while three studies showed a significant risk associated
      with sunscreen use. However, the discordant results, the low relative risks, the
      lack of dose-effect relationship and the numerous biases, especially the
      uncertainty that exposure (sunscreen use) preceded melanoma do not suggest a
      causative association between sunscreen use and melanoma. Several hypotheses
      could partly explain these contradictory results.

PMID- 11966730
TI  - Photoprotection: public campaigns in Ireland and the U.K.
AB  - Public education campaigns have been carried out in numerous countries in an
      effort to halt the rising numbers of skin cancers induced by sun exposure. Though
      the campaigns undoubtedly increase public awareness of skin cancer, in many
      countries, such awareness is not translated into alterations in behaviour in the
      sun. The public continues to rely on sunscreens as the main way of reducing sun
      exposure. Much education still remains to be translated into behaviour which will
      reduce skin cancer incidence. Education campaigns need to concentrate on positive
      aspects with perceived rewards which will then influence behaviour favourably as
      few people respond to negative messages with no immediate reward.

PMID- 11966731
TI  - Photoprotection: a 21st century perspective.

PMID- 11966733
TI  - A giant's step forward.

PMID- 11966734
TI  - The sodium iodide symporter and thyroid disease.

PMID- 11966735
TI  - Effects of GH replacement on 24-h ambulatory blood pressure and its circadian
      rhythm in adult GH deficiency.
AB  - OBJECTIVE: Increased prevalence of hypertension and cardiovascular mortality have
      been reported in hypopituitary patients who had been appropriately replaced with
      conventional pituitary hormones except GH. Growth hormone replacement (GHR)
      results in improvement of surrogate markers of cardiovascular function. Data on
      effects of GHR on blood pressure (BP) in adult growth hormone deficiency (AGHD),
      however, remain contradictory. There are as yet no reports on BP circadian
      rhythms in untreated or treated AGHD. Therefore, in a 12-month follow-up study,
      we evaluated the effects of GHR on ambulatory blood pressure (ABP) in AGHD
      patients. STUDY DESIGN: A prospective, open treatment design study to determine
      the effects of GHR on ABP and heart rate in AGHD patients. GH was commenced at a
      daily dose of 0.5 IU, and titrated up by increments of 0.25 IU at 4-weekly
      intervals to achieve and maintain IGF-I standard deviation score (IGF-I SD)
      between the median and upper end of the age-related reference range. PATIENTS:
      Twenty-two, post-pituitary surgery, severe AGHD patients (11 men), defined as
      peak GH response < 9 mU/l to provocative testing were recruited. The mean age +/-
      SEM was 48.8 +/- 2.5 years. Twenty-one patients required additional pituitary
      replacement hormones following pituitary surgery and were on optimal doses at
      recruitment. MEASUREMENTS: Twenty-four-hour ABP and heart rate (HR), body mass
      index (BMI), waist hip ratio (WHR) and total body water (TBW) were measured
      before and after 12 months on GHR. Cosinor analysis was used to analyse BP and HR
      circadian rhythm parameter estimates. RESULTS: Target IGF-I SD was achieved
      within 3 months of commencement of GHR in all patients (-3.5 +/- 0.4 at baseline
      vs. 0.8 +/- 0.2 at 3 months, P < 0.001) and remained within range at 12 months
      (1.1 +/- 0.2, P < 0.001 compared to baseline). A significant increase in TBW
      (45.8 +/- 1.2 vs. 47.8 +/- 1.5 kg, P < 0.05) but no significant change in BMI
      (30.7 +/- 2.2 vs. 31.8 +/- 2.7, P = NS) or WHR (0.95 +/- 0.02 vs. 0.93 +/- 0.02,
      P = NS) was observed after 12 months on GHR. The 24-h mean systolic ABP (SBP;
      126.2 +/- 2.8 vs. 120.1 +/- 2.7 mmHg, P < 0.001) and diastolic ABP (DBP; 78.2 +/-
      1.6 vs. 71.4 +/- 1.8 mmHg, P < 0.001) significantly decreased following GHR with
      a parallel increase in 24-h mean HR (69.6 +/- 2.5 vs. 73.8 +/- 2.5 beats/min; P <
      0.001). A significant nocturnal decrease in SBP and DBP was observed both before
      (SBP; daytime, 129.1 +/- 2.8 vs. night time, 115.9 +/- 3.0 mmHg, P < 0.001 and
      DBP; daytime, 80.7 +/- 1.6 vs. night time, 69.2 +/- 1.8 mmHg, P < 0.001) and
      following GHR (SBP; daytime, 122.8 +/- 2.6 vs. night time, 110.0 +/- 3.6 mmHg, P
      < 0.001 and DBP; daytime, 73.9 +/- 1.8 vs. night time, 62.0 +/- 2.3 mmHg, P <
      0.001). Individual and population-mean cosinor analysis demonstrated significant
      circadian rhythms for SBP, DBP and HR before and after 12 months on GHR (P <
      0.001), suggesting that SBP, DBP and HR circadian rhythms were not altered by
      GHR. There was, however, a significant reduction in SBP (124.2 +/- 2.8 vs. 118.4
      +/- 2.8 mmHg, P < 0.001) and DBP (77.0 +/- 1.6 vs. 70.2 +/- 1.8 mmHg, P < 0.001)
      MESOR with an increase in HR MESOR (68.9 +/- 2.5 vs. 72.2 +/- 2.4 beats/min, P <
      0.01) following GHR. CONCLUSIONS: Systolic and diastolic BP and HR circadian
      rhythms are preserved in AGHD following 12 months of GHR. However, there is a
      significant decrease in 24-h mean SBP and DBP and increase in 24-h mean HR after
      12 months on GHR. We postulate that this decrease in 24-h mean SBP and DBP may
      result in a reduction of cardiovascular morbidity and mortality and may explain
      the beneficial effects of GHR on cardiovascular system previously reported in
      AGHD patients.

PMID- 11966736
TI  - Skin fibroblasts of children with idiopathic short stature show an increased
      mitogenic response to IGF-I and secrete more IGFBP-3.
AB  - OBJECTIVE AND PATIENTS: To study differences in cellular parameters of GH and IGF
      I responsiveness in skin fibroblasts of 14 children with idiopathic short stature
      (ISS) treated with recombinant human GH and 13 children with normal height.
      Secondly, to investigate whether these cellular parameters can predict the growth
      response to GH treatment in children with ISS. DESIGN AND MEASUREMENTS: The
      mitogenic responsiveness to GH and IGF-I was investigated by 3H-Thymidine
      incorporation. Insulin-like growth factor binding protein-3 (IGFBP-3) levels in
      the media were measured by radioimmunoassay (RIA). RESULTS: No significant
      mitogenic responses were observed to various doses of GH (1000, 5000 or 50.000
      ng/ml) in children with ISS or controls. ISS fibroblasts showed an increased
      mitogenic response to IGF-I (10 ng/ml) compared to controls (mean +/- SD 5.9 +/-
      2.4- vs. 4.2 +/- 1.5-fold stimulation, P < 0.05), and GH enhanced this effect in
      both groups. IGFBP-3 secretion was increased in ISS fibroblasts when compared to
      controls under all conditions examined (basal, 200 and 5000 ng/ml GH, 10 ng/ml
      IGF-I for 24 and 48 h). High IGFBP-3 levels were related to low mitogenic
      responses to IGF-I or to GH + IGF-I in children with ISS (r = -0.7, P < 0.05),
      but not in controls. Within the ISS group, an enhanced mitogenic response to IGF
      I in vitro was related to more extreme short stature before GH treatment (r = 
      0.70, P < 0.05) and to a relatively impaired response to high dose GH treatment
      in vivo (r = -0.52, P < 0.05). CONCLUSION: The demonstration of high IGFBP-3
      levels and enhanced mitogenic response to IGF-I shows that ISS fibroblasts have
      different cellular characteristics compared to controls of normal height. It is
      hypothesized that in ISS an alteration of the signal transduction pathway between
      the GH receptor and IGFBP-3 synthesis results in a local imbalance with high
      IGFBP-3 levels and lower IGF-I availability for the IGF-I receptor. This may be
      reflected by an increased IGF-I responsiveness in vitro which is associated with
      an impaired capacity to grow in vivo.

PMID- 11966737
TI  - Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating
      capacity in hypopituitary adults with GH deficiency.
AB  - OBJECTIVES: Untreated growth hormone deficiency (GHD) is implicated in the
      increased cardiovascular risk associated with adult hypopituitarism. Oxidative
      stress, predisposing to lipid peroxidation, may be an important mediator of
      endothelial dysfunction, a pro-atherogenic state associated with adult GHD.
      DESIGN AND PATIENTS: In a randomized, double-blind, placebo-controlled study we
      investigated the effects of GH replacement on low-density lipoprotein (LDL)
      oxidation and neutrophil superoxide (O(-)(2)) generating capacity in 32 GHD
      adults (19 males, 13 females; age range 19-64 years) over 3 months. Thirty age-
      and sex-matched healthy controls were also studied. MEASUREMENTS: Lipid
      hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with
      xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed
      by the copper-catalysed lag phase of LDL oxidation. Neutrophil O(-)(2)-
      generating capacity was assessed by a lucigenin-based chemiluminescent assay of
      NADPH oxidase activity. Body composition was assessed using bioelectrical
      impedance analysis. RESULTS: Compared to controls, GHD subjects had higher LDL
      cholesterol (4.0 +/- 0.8 vs. 3.5 +/- 0.9 mmol/l, P < 0.01) and higher
      triglyceride concentrations (2.3 +/- 1.5 vs. 1.1 +/- 0.7 mmol/l, P < 0.001) but
      lower HDL cholesterol (1.1 +/- 0.3 mmol/l vs. 1.4 +/- 0.4 mmol/l, P < 0.01),
      lower levels of HPOs (0.72 +/- 0.35 vs. 0.92 +/- 0.20 microm, P < 0.01) and lower
      basal (2.5 +/- 1.5 vs. 4.5 +/- 2.3 mV/5 x 10(5) neutrophils, P < 0.01) and peak
      post-activation levels (23.2 +/- 11.1 vs. 34.4 +/- 15.6 mV/5 x 10(5) neutrophils,
      P < 0.01) of neutrophil O(-)(2)- generation. GH replacement resulted in an
      increase in HPOs from 0.70 +/- 0.39 to 0.86 +/- 0.19 microm (P < 0.05), although
      there was no change in the lag time of LDL oxidation. Neutrophil O(-)(2)-
      generating capacity was enhanced with a rise in basal O(-)(2)- generation from
      2.8 +/- 1.4 to 5.4 +/- 4.6 mV/5 x 10(5) neutrophils (P < 0.05) and in peak post
      activation O(-)(2)- generation from 21.9 +/- 9.5 to 35.8 +/- 21.7 mV/5 x 10(5)
      neutrophils (P < 0.05). LDL cholesterol was reduced from 4.1 +/- 0.8 mmol/l to
      3.5 +/- 0.8 mmol/l (P < 0.01). No significant changes in measured parameters
      occurred in the placebo group. CONCLUSIONS: Adult GHD is associated with reduced
      lipid peroxidation and impaired neutrophil O(-)(2)- generating capacity, both of
      which are reversible with GH replacement. Our data suggest that: (i) that
      oxidative stress is not a major feature of the pro-atherogenic state in
      hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil
      function and leucocyte-lipoprotein interactions.

PMID- 11966738
TI  - Genetic analysis of the MEN1 gene and HPRT2 locus in two Italian kindreds with
      familial isolated hyperparathyroidism.
AB  - OBJECTIVES: Familial hyperparathyroidism may occur as part of hereditary
      syndromes, including multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2A),
      hyperparathyroidism-jaw tumour (HPT-JT) syndrome and familial isolated
      hyperparathyroidism (FIHP). It is unclear whether the latter is a distinct
      genetic entity or a variant of MEN1 or HPT-JT, where, because of reduced
      penetrance, only primary hyperparathyroidism (PHPT) is present. In the present
      study, we describe two unrelated Italian kindreds with FIHP, in which the
      clinical, histopathological and genetic analyses of the MEN1 gene and HPRT2 locus
      at 1q21-32 suggest that both might be a variant of MEN1 and HPT-JT syndromes.
      PATIENTS AND DESIGN: We studied 16 members, aged 14-50 years, of two unrelated
      kindreds with FIHP. Genomic DNA was isolated from peripheral blood leucocytes in
      all family members, and from parathyroid tissue in those who underwent
      parathyroidectomy. MEASUREMENTS: Ionized calcium and PTH were measured in all
      family members. The nine coding exons and 16 splice junctions of the MEN1 gene
      from constitutional DNA were amplified by the polymerase chain reaction (PCR) and
      sequenced. Parathyroid glands were obtained from five subjects. Allelic deletions
      (loss of heterozygosity, LOH) of chromosomes 11q13 and 1q21-q32 were assessed
      using PYGM and D11S449, and D1S215, D1S222, D1S428, D1S412, D1S413 and D1S477,
      respectively. Forward primers were conjugated with 5' fluorescent dye. PCR
      products were analysed using an ABI PRISM 310 sequencer. RESULTS: Five members of
      family 1 and three of family 2 had PHPT. A heterozygous deletion of 1 bp of the
      MEN1 gene in exon 10 (1785delA) was found in affected members of family 1. No
      MEN1 gene mutation was found in any member of family 2. LOH at 11q13 was observed
      in family 1 tumours, but not in those from family 2. Studies at 1q21-32 showed
      LOH in two family 2 tumours, whereas a retained heterozygosity was found in the
      remaining member. No LOH at 1q21-32 was found in family 1 tumours. The pathology
      of family 1 showed chief cell hyperplasia with a diffuse-nodular pattern of
      growth. Cut surface showed no cystic structures. Typical parathyroid adenoma was
      diagnosed in one member of family 2 and atypical adenoma in the remaining two.
      These tumours showed cystic structures. CONCLUSIONS: In conclusion, we describe
      two unrelated kindreds with FIHP which, on the basis of histopathological and
      genetic studies, could be labelled as variants of the MEN1 and HPT-JT syndromes,
      respectively. Therefore, an extensive analysis of the genes involved in these
      diseases should be performed in families with familial isolated
      hyperparathyroidism to identify the subset linked to the MEN1 gene or to the
      HPRT2 locus.

PMID- 11966739
TI  - Mutational analysis of Portuguese families with multiple endocrine neoplasia type
      1 reveals large germline deletions.
AB  - OBJECTIVE: To determine the spectrum of MEN1 mutations in Portuguese kindreds,
      and identify mutation-carriers. PATIENTS, DESIGN AND RESULTS: Six unrelated MEN1
      families were studied for MEN1 gene mutations by single-strand conformational
      polymorphism (SSCP) and DNA sequence analysis of the coding region and exon
      intron boundaries of the MEN1 gene. These methods identified 4 different
      heterozygous mutations in four families: two mutations are novel (mt 1539 delG
      and mt 655 ims 11 bp) and two have been previously observed (mt 735 del 46p and
      mt 1656 del C) all resulting in a premature stop codon. In the remaining two
      families, in whom no mutations or abnormal MEN1 transcripts were detected,
      segregation studies of the 5' intragenic marker D11S4946 and codon 418
      polymorphism in exon 9 revealed two large germline deletions of the MEN1 gene.
      Southern blot and tumour loss of heterozygosity analysis confirmed and refined
      the limits of these deletions, which spanned the MEN1 gene at least from: exon 7
      to the 3' untranslated region, in one family, and the 5' polymorphic site
      D11S4946 to exon 9 (obliterating the initiation codon), in the other family.
      Twenty-six mutant-gene carriers were identified, 6 of which were asymptomatic.
      CONCLUSIONS: These results emphasize the importance of the detection of MEN1
      germline deletions in patients who do not have mutations of the coding region.
      Important clues indicating the presence of such deletions may be obtained by
      segregation studies using the intragenic polymorphisms D11S4946 and at codon 418.
      The detection of these mutations will help in the genetic counselling of clinical
      management of the MEN1 families in Portugal.

PMID- 11966740
TI  - A novel bioassay for human somatogenic activity in serum samples supports the
      clinical reliability of immunoassays.
AB  - OBJECTIVE: Because there is discordance between different immunoassay values for
      serum hGH, and because clinical state may not correlate with immunoreactive hGH,
      we have developed an assay to accurately measure serum hGH somatogenic
      bioactivity. The results of this assay were compared with the Elegance two-site
      ELISA assay across 135 patient samples in a variety of clinical states. DESIGN:
      The somatogenic assay was based on stable expression of hGH receptor in the
      murine BaF line, allowing these cells to proliferate in response to hGH. To
      eliminate interference by other growth factors in serum, we created a specific
      antagonist of the hGH receptor (similar to Trovert or Pegvisomant) which allowed
      us to obtain a true measure of hGH somatogenic activity by subtraction of the
      activity in the presence of the antagonist. The assay was carried out in
      microtiter plates over 24 h, with oxidation of a chromogenic tetrazolium salt
      (MTT) as the endpoint. PATIENTS: These encompassed a number of different clinical
      conditions related to short stature, including idiopathic short stature,
      neurosecretory dysfunction and renal failure, as well as obese patients on
      dietary restriction and normal volunteers. MEASUREMENTS: In addition to the
      colourimetric (MTT) response to hGH, we measured free hGH by stripping out GHBP
      bound hGH using beads coupled to a monoclonal antibody to the GHBP (GH binding
      protein). All samples were measured in both bioassay and ELISA assay. RESULTS:
      This bioassay was sensitive (5 mU/l or 2 microg/l) and precise, and not subject
      to interference by the GHBP. There was a good correlation (r = 0.95) between
      bioactivity and immunoactivity across clinical states. There was, however, an
      increased bioactivity during secretory peaks (over 25 mU/l), which has been
      reported previously for the Nb2 bioassay. Free hGH did not correlate with
      clinical state. CONCLUSIONS: Because the results of the Elegance ELISA and the
      bioassay correlate well, even though there is greater bioactivity at higher
      hormone concentrations, it is evident that an appropriate immunoassay is able to
      act as a reliable indicator for clinical assessment. In those rare cases where
      bio-inactive GH exists, our bioassay should provide an appropriate means to
      demonstrate this.

PMID- 11966741
TI  - Effect of withdrawal of somatostatin plus GH-releasing hormone as a stimulus of
      GH secretion in obesity.
AB  - OBJECTIVES: Somatostatin (SS) may not merely be inhibitory to GH secretion but,
      under appropriate temporal conditions, may act in a paradoxically positive manner
      to sensitize somatotroph responsiveness to GH-releasing hormone (GHRH). SS
      infusion withdrawal (SSIW) produces a rebound GH rise in humans and increases
      GHRH-induced GH release. Theoretically, SSIW leaves the somatotroph cell in a
      situation of low endogenous SS. In obesity, there is markedly decreased GH
      secretion. In both children and adults, the greater the body mass index (BMI),
      the lower the GH response to provocative stimuli. It has been postulated that
      increased hypothalamic somatostatin secretion is the main mechanism responsible
      for the blunted GH secretion of obesity. There are no data evaluating GH
      responsiveness to SSIW plus GHRH in obese adults. The aim of the present study
      was to evaluate the GH response to SSIW plus GHRH in a group of control subjects
      and a group of obese patients. PATIENTS AND MEASUREMENTS: Seven obese patients
      (six female, one male) with a BMI of 36.1 +/- 7.7 kg/m2 were studied. As a
      control group, seven normal subjects (six female, one male) with a BMI of 20.3 +/
      0.9 kg/m2 were also studied. Two tests were performed. On one day, somatostatin
      (SS) i.v. infusion (500 microg from 0-90 min) was performed followed by a placebo
      i.v. bolus 90 min after SS withdrawal (SSIW). On another day, SS i.v. infusion
      (500 microg from 0-90 min) was performed followed by a GHRH (100 microg) i.v.
      bolus 90 min after SS withdrawal. A second group of seven obese patients (six
      female, one male) with a BMI of 32.2 +/- 2.3 kg/m2 were studied. As a second
      control group, seven normal healthy subjects (six female, one male) with a BMI of
      20.1 +/- 0.6 kg/m2 were also studied. On one day, saline infusion was performed
      followed by a placebo i.v. bolus at 90 min. On another day, saline infusion was
      performed followed by a GHRH (100 microg) i.v. bolus at 90 min. Blood samples
      were taken at appropriate intervals for determination of GH. Serum GH was
      measured by chemiluminescent immunometric assay. Statistical analysis was
      performed by Wilcoxon and Mann-Whitney tests. RESULTS: GHRH-induced GH secretion
      in normal subjects showed a mean peak of 15.8 +/- 2.1 microg/l. Normal control
      subjects had a mean peak of 3.1 +/- 1.5 microg/l after SSIW-induced GH secretion.
      When GHRH was administered after SSIW there was an increased GH secretion with a
      mean peak of 23.3 +/- 4.4 microg/l, significantly greater than the response after
      SSIW alone (P < 0.05) and GHRH alone (P < 0.05). GHRH-induced GH secretion in
      obese patients was decreased with a mean peak of 3.9 +/- 1.5 microg/l. In obese
      patients, GH secretion after SSIW was markedly decreased with a mean peak of 1.0
      +/- 0.4 microg/l. When GHRH was administered after SSIW, an increase in GH
      secretion was observed with a mean peak of 4.3 +/- 0.9 microg/l, significantly
      greater than SSIW alone (P < 0.05) but not GHRH alone (P = NS), and significantly
      less than in normal subjects (P < 0.05). CONCLUSIONS: This study demonstrates a
      significantly blunted peak GH response to somatostatin infusion withdrawal plus
      GHRH in obese patients compared to normal subjects. In this theoretical situation
      of decreased somatostatinergic tone, there is persistence of GH hyposecretion in
      obesity, suggesting the existence of multiple defects responsible for decreased
      GH secretion in obesity. We also found that in obese patients, in contrast to
      normal subjects, SSIW did not increase GHRH-induced GH secretion.

PMID- 11966742
TI  - Effects of GH replacement on endothelial function and large-artery stiffness in
      GH-deficient adults: a randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVES: Hypopituitary adults with growth hormone deficiency (GHD) have an
      increased cardiovascular mortality, although the mechanisms remain unclear.
      Endothelial dysfunction, characterized by reduced nitric oxide (NO)
      bioavailability, is a key early event in atherogenesis and is associated with
      increased vascular smooth muscle tone and arterial stiffening. DESIGN AND
      PATIENTS: In a randomized, double-blind, placebo-controlled study, we
      investigated the effects of GH replacement on endothelial function and large
      artery stiffness in 32 GHD adults (19 males, 13 females) (age range 19-64 years)
      over a 6-month period. Thirty-two age- and sex-matched healthy controls were also
      studied. MEASUREMENTS: Endothelial function was assessed using ultrasonic wall
      tracking to measure flow-mediated dilatation (FMD) of the brachial artery. Large
      artery stiffness was assessed by pulse wave analysis of the radial artery
      pressure waveform, allowing determination of the corresponding central arterial
      pressure waveform and derivation of the augmentation index. Fasting lipid
      profiles, glucose and insulin were also measured. RESULTS: At baseline, FMD (mean
      +/- SD) was impaired in GH-deficient subjects vs. controls (3.4 +/- 2.3 vs. 5.7
      +/- 2.0%, P < 0.0001), although endothelium-independent dilatation was similar.
      The augmentation index was higher in GH-deficient subjects vs. controls (23 +/-
      12 vs. 14 +/- 14%, P < 0.01). GH-deficient subjects had higher LDL cholesterol
      (4.1 +/- 0.8 vs. 3.5 +/- 0.8 mmol/l, P < 0.01) and lower HDL cholesterol (1.1 +/-
      0.3 vs. 1.4 +/- 0.4 mmol/l, P < 0.01). In GH-deficient subjects, there were
      inverse correlations between LDL cholesterol and FMD (r = -0.40, P < 0.05) and
      between FMD and the augmentation index (r = - 0.58, P < 0.01). Regression
      analysis identified FMD as an independent predictor of the augmentation index (P
      < 0.0001). In comparison with baseline, GH replacement resulted in an increase in
      FMD (5.0 +/- 2.6 vs. 2.8 +/- 1.9%, P < 0.01). There were decreases in central
      aortic systolic pressure (117 +/- 15 vs. 123 +/- 17 mmHg, P < 0.01), diastolic
      pressure (82 +/- 10 vs. 86 +/- 8 mmHg, P < 0.01) and the augmentation index (22
      +/- 8% vs. 26 +/- 10%, P < 0.05) despite unchanged brachial pressure indices. LDL
      cholesterol also decreased (3.5 +/- 0.8 vs. 4.2 +/- 0.8 mmol/l, P < 0.01). There
      were no significant changes in the placebo group. CONCLUSIONS: Adult GHD is
      associated with endothelial dysfunction and increased large-artery stiffness. An
      improvement in endothelial function and a reduction in arterial stiffness
      following GH replacement suggests an important therapeutic role for GH in
      reducing cardiovascular risk associated with adult GHD.

PMID- 11966743
TI  - Confirmation of severe GH deficiency after final height in patients diagnosed as
      GH deficient during childhood.
AB  - OBJECTIVE: Human GH treatment of patients with childhood-onset (CO) growth
      hormone deficiency (GHD) ceases when they reach final height; this provides an
      opportunity to retest GH status in all patients before determining whether GH
      therapy will be required in adult life. At present, the diagnostic approach to
      these patients is not fully standardized. This study aimed to characterize a
      large group of previously GH-treated CO GHD patients and establish their GH
      status. PATIENTS AND METHODS: The multinational study included 167 patients
      diagnosed as GH deficient and treated with hGH to final height during childhood.
      Mean age was 19.2 years and mean height standard deviation score (SDS) was -1.08.
      Peak serum GH concentrations were determined in standard GH stimulation tests.
      IGF-I and IGFBP-3 concentrations were determined at a central laboratory and
      converted to SDS values by reference to a normal population. RESULTS: Using only
      a peak GH value of less than 3 microg/l (1 mg = 3 U) in stimulation tests as the
      cut-off, 133 (79.6%) patients would be classed as GH deficient. Using only an IGF
      I value less than -2 SDS as the cut-off, 134 (80.2%) patients would be classed as
      GH deficient. However, by using both criteria there were 120 (71.9%) patients who
      were definitely severely GH deficient (group 1) and 20 (12.0%) who were not GH
      deficient (group 2), leaving 14 (8.4%) classed as GH deficient from IGF-I SDS
      only (group 3) and 13 (7.8%) classed as GH deficient from stimulation test only
      (group 4). There was no difference between the groups in height SDS or body mass
      index (BMI), but the GH-deficient patients tended to have been diagnosed at a
      younger age (group 1, 8.2 +/- 3.9; group 2, 10.0 +/- 4.0; P = 0.052). For
      patients classed as GH deficient compared with those not GH deficient, the
      percentage of males was lower (group 1, 64.2%; group 2, 90.0%; P = 0.022) and the
      percentage with multiple pituitary hormone deficiencies was higher (group 1,
      81.7%; group 2, 20.0%; P < 0 .001), with the other two groups being intermediate
      in each case. Only the group classed as GH deficient by both criteria had a mean
      IGFBP-3 less than -2 SDS and both IGF-I SDS and IGFBP-3 SDS increased steadily
      across the four groups. CONCLUSIONS: A high percentage (71.9%) of these childhood
      onset GH-deficient patients were still GH deficient in adult life and are likely
      to require further hGH treatment. While 12.0% could be classed as definitely no
      longer GH deficient, there are some patients who are intermediate (16.2%) and may
      be classed as GH deficient by one criterion but not the other. When GH
      stimulation test results and IGF-I concentration are discordant, the IGFBP-3
      level does not establish diagnosis and the hGH treatment requirement of such
      patients remains a dilemma.

PMID- 11966744
TI  - FSH and ovarian response: spontaneous recovery of pituitary-ovarian activity
      during the pill-free period vs. exogenous recombinant FSH during high-dose
      combined oral contraceptives.
AB  - OBJECTIVE: Compare spontaneous recovery of pituitary-ovarian activity during the
      pill-free period following the correct use of low-dose oral contraceptives and
      subsequent ovarian function during the administration of exogenous recombinant
      FSH (recFSH) after switching to continued Lyndiol (2.5 mg lynestrenol + 0.05 mg
      ethinyl-oestradiol) medication. DESIGN: Prospective, randomized, group
      comparative, single-centre study. Following the monitoring of the pill-free
      period (week 1) and subsequent treatment with Lyndiol (for a total of 5 weeks),
      all subjects were randomly allocated to one of four groups receiving daily FSH
      injections for 1 week [75, 150, 225 IU recFSH or 150 IU purified urinary FSH
      (uFSH)] during the fourth week of Lyndiol use. PATIENTS: Thirty-six healthy
      volunteers aged 18-39 years, prestudy oral contraceptive use for at least 3
      months, cycle length between 24 and 35 days. MEASUREMENTS: Serum FSH, LH and
      oestradiol (E2) concentrations as well as transvaginal ultrasound assessment of
      the number and diameter of follicles > 2 mm were used to monitor pituitary
      ovarian function. RESULTS: At the start of the pill-free period following the
      prestudy contraceptive medication, 67% of the women presented with LH and FSH
      levels < 1 IU/l and only one follicle > 10 mm was observed. Initial levels of LH
      and FSH correlated (P < 0.05) with the extent of pituitary-ovarian activity
      during the pill-free period. At the end of the pill-free period a follicle > 10
      mm had emerged in one subject only. During the first 3 days of Lyndiol use, seven
      women (19%) eventually showed at least one follicle > 10 mm. During combined
      exogenous FSH and Lyndiol administration, LH levels remained completely
      suppressed (< or = 0.5 IU/l) in all women studied. FSH levels and number and size
      of follicles increased with increasing doses of exogenous FSH in a dose-dependent
      manner. E2 levels remained low in all groups (< 150 pmol/l). During the week
      following FSH administration, FSH levels and E2 levels decreased gradually while
      the number of follicles > 10 mm still increased. CONCLUSIONS: We have confirmed
      that dominant follicles > 10 mm are present at the end of the pill-free period
      and during the first days after resumption of pill intake. Once follicles > 10 mm
      arose at the end of the pill-free period, continued use of Lyndiol did not reduce
      follicle diameters. One week of Lyndiol reduces pituitary-ovarian activity to
      levels observed after 3 weeks of low-dose pills. FSH administration during
      Lyndiol resulted in dose-dependent follicle growth despite extremely low LH
      levels. E2 secretion (56 +/- 51 pmol/l) occurred to a limited and variable extent
      along with extremely low serum LH concentrations. Recovery of pituitary-ovarian
      activity at the end of the pill-free period is comparable to FSH levels and
      follicle dynamics following 7 days of 75-150 IU/l recFSH.

PMID- 11966745
TI  - Reduced capillary permeability and capillary density in the skin of GH-deficient
      adults: improvement after 12 months GH replacement.
AB  - OBJECTIVE: Several lines of evidence suggest that the GH-IGF-1 axis affects
      capillary permeability and angiogenesis. We evaluated skin capillary permeability
      and capillary density in GH-deficient adults, before and after GH replacement
      therapy. PATIENTS: Seven normotensive, nondiabetic GH-deficient adults (two
      women) were matched with 14 control subjects. MEASUREMENTS: Large-window
      videodensitometry with sodium fluorescein was performed in all subjects.
      Capillary permeability was expressed as the average relative light intensity over
      the first 7 min after the appearance of fluorescein in the skin capillaries;
      Iav(7). Skin capillary density was determined by counting the visualized
      capillaries and was expressed as n/mm2. The GH-deficient patients were restudied
      after 12 months of GH replacement therapy (2 U/day). RESULTS: Both capillary
      permeability and capillary density were lower in untreated GH-deficient patients
      than in control subjects (median, interquartile range): Iav(7) in GH-deficient
      patients 47.1 (45.1-52.2)% vs. 57.5 (50.5-64.8)% in controls, P < 0.05; capillary
      density in GH-deficient patients 18 (12-24)/mm2 vs. 32 (26-36)/mm2 in controls, P
      < 0.05. GH treatment normalized plasma IGF-1 from 4.3 (1.0-13.4) to 22.2 (19.8
      48.2) nmol/l (P < 0.05). Furthermore, both capillary permeability [Iav(7) 53.1
      (48.8-58.4)%, P < 0.05] and capillary density [26 (17-34)/mm2, P < 0.05]
      increased to a level that was not different from that in control subjects.
      CONCLUSIONS: The present study demonstrates that the growth hormone deficiency
      syndrome is associated with microvascular alterations, which are responsive to
      growth hormone replacement therapy.

PMID- 11966746
TI  - Low-dose GH replacement improves the adverse lipid profile associated with the
      adult GH deficiency syndrome.
AB  - OBJECTIVE: Adult growth hormone deficiency (AGHD) is associated with an adverse
      lipid profile. The majority of previous studies of GH replacement have used
      supraphysiological doses and reported favourable changes in the lipid profile.
      Whether this beneficial effect is the result of pharmacological GH therapy, or
      occurs in response to low-dose GH replacement aimed at normalization of the serum
      IGF-I, has not been fully elucidated. STUDY DESIGN: We studied 67 patients with
      GH deficiency using a low-dose individualized GH replacement regimen. GH was
      commenced at a dose of 0.27 mg/day and the GH dose titrated until the serum IGF-I
      was normalized. Serum lipids were assessed at baseline, 12 and 24 months.
      RESULTS: A reduction in total cholesterol (TC) was observed at 12 (6.01 vs. 5.77
      mmol, P = 0.04) and 24 months (6.01 vs. 5.56, P = 0.09). The reduction in LDLC
      failed to reach significance at 12 months (3.97 vs. 3.8, P = 0.09), but was
      significant at 24 months (3.97 vs. 3.50, P = 0.02). Levels of HDLC did not change
      significantly at 12 or 24 months. Significant improvements in the TC/HDLC ratio
      were observed at both 12 (5.68 vs. 5.29, P = 0.01) and 24 months (5.68 vs. 4.86,
      P = 0.007). A significant fall in triglycerides (TG) was present at 12 months
      (2.07 vs. 1.83, P = 0.01), and was maintained at 24 months, but was no longer
      significant (2.07 vs. 1.89, P = 0.28). At 12 months there was no correlation
      between improvements in lipid parameters and either the change in IGF-I SD score
      or the GH dose. Using multivariate analysis the change in TC, LDLC and the
      TC/HDLC ratio with 12 months GH replacement were determined by the baseline TC,
      LDLC and TC/HDLC levels (R2 = 0.18, P = 0.004; R2 = 0.20, P = 0.006; and R2 =
      0.33, P < 0.0001), respectively. CONCLUSIONS: Low-dose individualized GH
      replacement aimed at normalization of the serum IGF-I is associated with
      significant improvements in TC, LDLC, TGs and the TC/HDLC ratio. The greatest
      improvements are observed in patients with the most adverse lipid profiles at
      baseline. Improvements are independent of changes in the IGF-I SDS and GH dose.

PMID- 11966747
TI  - The low-dose ACTH test does not provide a useful assessment of the hypothalamic
      pituitary-adrenal axis in secondary adrenal insufficiency.
AB  - OBJECTIVE: The 1 microg ACTH stimulation test has been introduced to improve the
      sensitivity of ACTH as a test of the integrity of hypothalamic-pituitary-adrenal
      axis (HPAA). This study aims to compare the sensitivity, specificity and
      diagnostic accuracy of the "low-dose" 1 microg ACTH (LDACTH) test and the
      "standard dose" 250 microg ACTH (SDACTH) test, with the overnight metyrapone test
      (OMT) which assesses the entire HPAA. DESIGN: A prospective evaluation of the
      performance of SDACTH and LDACTH screening tests in a diverse cohort of patients
      with possible adrenal insufficiency as routinely encountered in clinical practice
      using the OMT as the reference method. PATIENTS: A total of 51 patients (26 with
      asthma on inhaled glucocorticoid, nine with hypopituitarism, three with
      hypothyroidism, one with hyponatraemia, one with Crohn's disease, one with
      encephalitis and 10 with non-specific symptoms) each underwent SDACTH, LDACTH and
      OMT tests in random sequence at least 1 week apart. MEASUREMENTS: Blood was
      sampled for plasma cortisol levels at 0 and 30 min after intravenous
      administration of 1 microg and 250 microg of ACTH. Metyrapone 30 mg/kg body
      weight was taken orally at midnight, and plasma samples were taken for
      measurement of 11-deoxycortisol and cortisol next morning between 08.00 and 09.00
      h. The OMT was deemed to be abnormal when both 11-deoxycortisol and cortisol
      levels were less than 200 nmol/l. RESULTS: The sensitivity and specificity at an
      empirical "normal" plasma cortisol threshold value of 500 nmol/l were 67% and
      100% for the SDACTH test, and 73% and 81% for the LDACTH test, respectively. As
      the plasma cortisol cut-off value was increased to 550 nmol/l and 600 nmol/l, the
      sensitivity of the SDACTH test was 67% and 80% and specificity was 97% and 92%,
      respectively. The sensitivity of the LDACTH test increased from 93% at plasma
      cortisol cut-off value of 550 nmol/l to 100% at plasma cortisol cut-off value of
      600 nmol/l. However, the specificity of the LDACTH test fell from 72% to 56% as
      the plasma cortisol cut-off value was increased from 550 nmol/l to 600 nmol/l. A
      receiver operating characteristic curve demonstrated that the specificity of the
      SDACTH test was higher than the specificity of the LDACTH test at any given level
      of sensitivity. CONCLUSIONS: Both the LDACTH and SDACTH tests fail to achieve
      acceptable levels of sensitivity and specificity to be useful as screening tests
      for secondary adrenal insufficiency. In this context the OMT can be safely used
      to assess the integrity of the entire HPAA.

PMID- 11966748
TI  - Long-term follow-up results of transsphenoidal surgery for Cushing's disease in a
      single centre using strict criteria for remission.
AB  - OBJECTIVE: Transsphenoidal selective adenomectomy (TSA) is widely accepted as the
      treatment of choice for Cushing's disease but not all patients are cured by this
      procedure. The success of surgery depends on the skill and experience of the
      surgeon but the criteria used to define remission are highly variable. We have
      analysed the outcome following surgery in our centre using the stringent
      requirement of a postoperative serum cortisol of < 50 nmol/l as our definition of
      remission and assessed whether changes in surgical policy, including a greater
      emphasis on selective procedures and the move in recent years to a single surgeon
      undertaking all pituitary surgery, have improved complication and remission
      rates. PATIENTS AND METHODS: The case notes, histology and pituitary imaging of
      54 consecutive patients (42 females, mean age 41 years) with pituitary-dependent
      Cushing's syndrome who had undergone transsphenoidal surgery between January 1980
      and November 2000 were reviewed. Follow-up was for a median of 6 years (range 6
      months to 21 years). RESULTS: One patient died within 1 week of surgery (1.9%)
      and major morbidity occurred in eight patients (15%). Clinical and biochemical
      remission was achieved in 41 patients (77%) with only two recurrences (5%) to
      date. Success was related to tumour size with 37 (86%) of 43 intrasellar lesions
      successfully resected compared with only four (40%) of 10 extrasellar adenomas.
      Twenty-four (59%) of those in remission developed partial or complete
      hypopituitarism compared with four (33%) of those not in remission. The extent of
      surgical exploration predicted the development of hypopituitarism (88% total
      hypophysectomy, 33% hemihypophysectomy, 14% selective adenomectomy) but not
      remission (75% total hypophysectomy, 87% hemihypophysectomy, 71% selective
      adenomectomy). Among complications, an excess of venous thromboembolic disease
      was noted, with three patients (6%) developing deep venous thrombosis or
      pulmonary embolism postoperatively. Comparison of the data for individual
      surgeons revealed an improvement in outcome over time, with 100% remission of
      microadenomas, 29% hypopituitarism and 12% complications following the move to a
      single surgeon undertaking all pituitary surgery. CONCLUSION: Transsphenoidal
      surgery is a safe and effective treatment for Cushing's disease and our results
      compare favourably with those from published series, the majority of which
      comprise relatively small numbers. The presence of an intrasellar lesion and
      postoperative serum cortisol < 50 nmol/l are good predictors of remission in the
      long term but historically in our centre this can only be achieved in a
      significant number of patients at the expense of some degree of hypopituitarism.
      However, the surgical outcome for Cushing's disease, including a reduced
      frequency of hypopituitarism, can be improved if patients are operated on by a
      single pituitary surgeon, using selective adenomectomy as the preferred surgical
      approach wherever possible.

PMID- 11966749
TI  - Anaplastic pseudothyroiditis.
AB  - Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumours.
      It generally presents as a rapidly enlarging thyroid mass and produces local
      symptoms associated with mass effect. One of the very rare presentations of ATC
      is thyrotoxicosis. We report a patient with ATC whose course was complicated by
      severe thyrotoxicosis. His symptoms were controlled with beta-blockers. Two weeks
      into hospitalization, the patient became hypothyroid. Histopathology showed
      destruction of the normal thyroid follicles by the invasion of the tumour. As
      this form of thyrotoxicosis resembles various thyroiditides, we hereby refer this
      condition as "anaplastic pseudothyroiditis".

PMID- 11966750
TI  - Radio-frequency ablation for symptom control in a patient with metastatic
      pancreatic insulinoma.
AB  - Malignant insulinomas are very rare endocrine tumours with a variable clinical
      course. We describe a 51-year-old man who had two large insulinomas resected from
      the body of the pancreas and 19 years later, having again become symptomatic, was
      found to have hepatic metastases. Medical treatment with diazoxide and octreotide
      failed to control his symptoms, but repeated hepatic embolization effected both
      symptomatic and biochemical improvements for a further 5 years. When symptoms
      recurred but further embolization failed to control his symptoms the hepatic
      metastases were treated by outpatient percutaneous radio-frequency ablation. He
      remains symptom-free 18 months later and levels of insulin and pro-insulin have
      nearly normalized. The survival, with liver metastases, for 27 years in a man
      with a malignant insulinoma has not been described previously. Malignant
      insulinoma may follow a rather indolent course and symptoms respond well to
      locally destructive therapies. Hepatic embolization is less traumatic than
      hepatic lobe resection and radio-frequency ablation offers an alternative if
      vascular access to the tumour is no longer possible.

PMID- 11966751
TI  - An audit of adult women with Turner's syndrome--is surveillance for comorbidity
      adequate?

PMID- 11966752
TI  - Does normalization of prolactin levels result in weight loss in patients with
      prolactin secreting pituitary adenomas?

PMID- 11966754
TI  - For further investigations in IgA nephropathy the approach from phenotype to
      genotype is welcome.

PMID- 11966756
TI  - Feeding NOD mice with pig splenocytes induces transferable mechanisms that
      modulate cellular and humoral xenogeneic reactions against pig spleen or islet
      cells.
AB  - We have reported previously that oral administration of pig cells to NOD mice
      modified xenogeneic cellular response against pig islet cells (PICs), and
      hypothesized that it may have induced active suppression. This preliminary report
      evaluated only the effect of feeding pig cells by 'primary' proliferation, i.e.
      when splenocytes from fed mice are confronted with pig cells in vitro. The
      present study also considered 'secondary' proliferation and cytokine production
      after feeding and subsequent in vivo graft of pig cells. Additionally, serum IgM
      and IgG isotypes were quantified by ELISA using pig target cells. Induction of
      active mechanism by feeding was hypothetical, which led us here to transfer
      splenocytes from mice fed pig spleen cells (PSC) and evaluate 'primary' (after
      transfer) and 'secondary' (after transfer and subsequent graft of pig cells)
      proliferations and cytokine secretions in recipient mice. We also determined
      whether the effects of feeding pig cells persisted after depression of suppressor
      mechanisms by cyclophosphamide. Mice fed with PSC displayed increased 'primary'
      splenocyte proliferation to PSC or PIC (P < 0.0001), while 'secondary' responses
      were decreased (P < 0.03) in those fed PSC and subsequently grafted with PSC. The
      increased 'primary' and decreased 'secondary' proliferations were reduced (P <
      0.04) by pretreatment with cyclophosphamide. The IL-10/ and IL-4/IFNgamma ratios
      produced in response to PSC increased (P < 0.04) in mice fed and grafted with PSC
      compared to those grafted only with PSC. IgM and IgG levels against pig cells
      were, respectively, increased (P < 0.04) and decreased (P < 0.04) in mice fed and
      grafted with PSC. IgG2a and IgG2b, but not IgG1, levels were lower (P < 0.01).
      These effects of feeding PSC on 'secondary' proliferation, cytokine and antibody
      productions, were not detected when mice were fed PSC only after graft with PSC.
      Transfer with splenocytes from mice fed PSC increased 'primary' proliferation of
      splenocytes from recipient mice in response to PSC (P < 0.02) or PIC (P < 0.05).
      After transfer with splenocytes from PSC-fed mice and graft with PSC, 'secondary'
      proliferation to pig cells were reduced (P < 0.04), and the IL-10/IFNgamma ratio
      produced in response to PSC was increased fourfold. Thus, oral administration of
      PSC induces active transferable mechanisms, characterized by a biphasic pattern
      with early increased 'primary' xenogeneic cellular reactions to both PSC and PIC,
      followed by decreased 'secondary' responsiveness and a concomitant shift of the
      Th1/Th2 balance towards greater Th2 influence. Decreased responsiveness may be
      due to active suppression, even though induction of anergy or deletion cannot be
      excluded.

PMID- 11966757
TI  - The in vivo effects of tumour necrosis factor blockade on the early cell mediated
      immune events and syndrome expression in rat adjuvant arthritis.
AB  - Anti-TNF therapy is effective in rheumatoid arthritis (RA); however, its
      mechanisms of action are incompletely understood. T cell-driven mechanisms are
      thought to play an important role in RA and the effects of TNF blockade on these
      mechanisms are unclear. Adjuvant arthritis (AA) is a T cell dependent model of
      inflammatory arthritis. The aims of this study were to investigate the effects of
      TNF blockade on in vivo T cell cytokine expression and to clarify the role of TNF
      in the inguinal lymph nodes (ILN) in early arthritis. AA was induced in male DA
      rats. Rats received either 3 mg/kg or 10 mg/kg PEG sTNF-RI at days 0, 2 and 4
      postinduction or 10 mg/kg anti-TNF antibody on day of arthritis induction.
      Control rats received either saline or normal sheep serum. Paw volume was
      assessed every 3-4 days. Rats were sacrificed on days 0, 6, 13 and 21
      postinduction. Ankles were removed for quantitative radiology and histology.
      Synovium and ILN were removed for cell culture and to determine mRNA expression
      of cytokines using semiquantitative RT-PCR. TNF and IFN-gamma protein production
      was measured using a bioassay and an ELISA. TNF blockade did not suppress mRNA
      expression of T cell cytokines in the ILN of rats in the early phase of AA,
      suggesting ongoing T cell activity. TNF protein production by ILN cells in
      culture was reduced in PEG sTNF-RI treated rats, although mRNA expression was
      increased in the ILN prior to culture. Early administration of PEG sTNF-RI did
      not attenuate AA, in contrast to an anti-TNF antibody, which suppressed disease.
      A shorter half-life for the PEG sTNF-RI compared with the anti-TNF antibody or
      the development of anti-PEG sTNF-RI antibodies may account for these results.

PMID- 11966755
TI  - Prospects for immune reconstitution in HIV-1 infection.

PMID- 11966758
TI  - The arthritogenic adjuvant squalene does not accumulate in joints, but gives rise
      to pathogenic cells in both draining and non-draining lymph nodes.
AB  - A single intradermal injection of the adjuvant-oil squalene induces T cell
      mediated arthritis in DA rats. The chain of events leading from non-specific
      provocation of the immune system to arthritis, with clinical similarities to
      rheumatoid arthritis, is largely undetermined. Here, we combined in vivo tracking
      of tritium-labelled squalene with lymph node (LN) cell transfer experiments to
      determine where critical activation events may take place. The majority of
      squalene remained at the injection site (79%). The amounts recovered in
      peripheral joints (<1%) were equal to that recovered in other organs that can be
      targets in autoimmune diseases. This argues that arthritis does not develop as a
      consequence of adjuvant accumulation in joints. In contrast, substantial amounts
      of squalene were recovered in hyperplastic LN draining the injection site (1
      13%). The adjuvant was deposited to a larger extent in cells than in
      extracellular matrix. The draining LN cells could transfer arthritis to naive
      irradiated DA rats following in vitro stimulation with conA. Interestingly, non
      draining LN were also hyperplastic and harboured arthritogenic cells, although
      they contained low amounts of squalene (<1%). Consequently, the amount of
      arthritogenic adjuvant in a particular LN is not closely linked to the
      development of pathogenic cells. The distribution pattern of squalene was similar
      in MHC-identical but arthritis-resistant PVG.1AV1 and LEW.1AV1 rats, and it was
      unaffected by T cell depletion with a monoclonal antibody (R73). Thus, T cells
      and non-MHC genes do not regulate dissemination of squalene, but rather determine
      arthritis development at the level of adjuvant response.

PMID- 11966759
TI  - Leucocyte chemotaxis: Examination of mitogen-activated protein kinase and
      phosphoinositide 3-kinase activation by Monocyte Chemoattractant Proteins-1, -2, 
      3 and -4.
AB  - Monocyte Chemoattractant Proteins (MCPs) form a distinct, structurally-related
      subclass of CC chemokines. They are major chemoattractants for monocytes and T
      lymphocytes. The MCPs bind to specific G-protein-coupled receptors, initiating a
      signal cascade within the cell. Though the signal transduction pathways involved
      in MCP-1-mediated chemotaxis have been studied, the signalling pathways through
      which MCP-2, -3 and -4 trigger cell migration are not established. In this study,
      we examined the mitogen-activated protein kinase (MAPK) activation elicited by
      the MCPs (1-4) and its specific role in chemotaxis. Within 2 min, the MCPs (1-4)
      elicited a rapid and transient activation of MAPK in peripheral blood mononuclear
      cells and in HEK-293 cells expressing CCR2b. U0126, an inhibitor of MAPK-kinase
      (MEK) activation, not only prevented extracellular signal-regulated kinase 1/2
      (ERK1/2) activation but also significantly inhibited the MCP-mediated chemotaxis.
      PI3K inhibitors Wortmannin and LY294002 also partially inhibited the MCP-induced
      chemotaxis. However, these compounds did not significantly inhibit ERK1/2
      activation. As PI3K inhibitors partially inhibit the MCP-mediated chemotaxis but
      do not significantly effect ERK1/2 activation, these data suggest that co
      ordinated action of distinct signal pathways is required to produce chemokine
      mediated chemotaxis.

PMID- 11966761
TI  - Adhesion to fibronectin via alpha4 integrin (CD49d) protects B cells from
      apoptosis induced by serum deprivation but not via IgM or Fas/Apo-1 receptors.
AB  - Apoptosis is a regulated event crucial to the development and proliferation of
      normal and malignant B cells. We have studied the role of signals delivered via
      alpha4 integrin on apoptosis triggered by three different pathways on these
      cells. For apoptosis induced by serum deprivation, culturing B cells on the
      recombinant fibronectin fragment H89, a known ligand for alpha4beta1 integrin,
      resulted in statistically significant (P < 0.005) higher viability values (68%,
      65% and 67%) for Ramos, Nalm-6 and EHEB cells, respectively, than culturing cells
      on poly lysine (42%, 42% and 48%). An antialpha4 MoAb reverted the protecting
      effect, thus confirming that it was due specifically to alpha4 engagement.
      Similarly, cells cultured on FN-III4-5, a recently identified fibronectin region
      which binds activated alpha4 integrin, also showed statistically significant
      higher viability than poly lysine cultures. Alpha4 engagement however, did not
      prevent apoptosis induced on Ramos cells via surface IgM. Adhesion of IM-9 cells,
      a myeloma cell line carrying functional Fas receptors, to the H89 fragment
      neither increased cell viability upon triggering apoptosis via Fas when compared
      to poly lysine. These results indicate that alpha4 signalling may overcome B cell
      apoptosis induced by the lack of growth factors but does not seem to affect the
      IgM or Fas apoptotic pathways, thus suggesting different intracellular mechanisms
      for these processes.

PMID- 11966760
TI  - Intravenous immunoglobulin (IVIG) preparations induce apoptosis in TNF-alpha
      stimulated endothelial cells via a mitochondria-dependent pathway.
AB  - Endothelial cells (ECs) are a target in inflammation, and the death of EC is
      regulated by various factors. Although intravenous immunoglobulin (IVIG)
      preparations are known to be beneficial therapeutic agents for the treatment of
      autoimmune diseases and systemic inflammatory disorders, their mechanism of
      action have not yet been completely elucidated. The aim of the present study is
      to investigate the possible role of IVIG in EC apoptosis. We demonstrate herein
      that IVIG induced the apoptosis of human umbilical vein ECs (HUVECs)
      prestimulated by TNF-alpha in vitro, but not in unstimulated HUVECs, in a dose-
      and time-dependent manner, using a proportion of cells with hypodiploid DNA, DNA
      ladder formation and morphological changes. Anti-Fas MoAbs had no effect on the
      IVIG-induced apoptosis in the TNF-alpha-stimulated HUVECs. IVIG decreased the
      intracellular expression of anti-apoptotic proteins of the Bcl-2 family (A1 and
      Bcl-XL) while IVIG increased the intracellular expression of pro-apoptotic
      proteins (Bax and Bcl-XS) in the TNF-alpha-stimulated HUVECs. Furthermore, IVIG
      increased the intracellular production of reactive oxygen species and decreased
      the mitochondrial membrane potential (Delta(psi)m). Caspase-inhibitors inhibited
      the IVIG-induced apoptosis of the TNF-alpha-stimulated HUVECs. The present
      results show a novel action in which IVIG can induce the apoptosis of TNF-alpha
      stimulated HUVECs through a mitochondrial apoptotic signalling pathway. These
      observations suggest that the clinical use of IVIG preparations may thereby
      regulate the cell death of activated ECs in inflammation.

PMID- 11966762
TI  - The effects of chromium and copper supplementation on mitogen-stimulated T cell
      proliferation in hypercholesterolaemic postmenopausal women.
AB  - The purpose of this study was to analyse effects of chromium and/or copper
      supplementation on immune function in hypercholesterolaemic postmenopausal women.
      A 2 x 2 factorial research design was used and 40 subjects were supplemented with
      0.394 g lactose, 200 microg Cr, 3.0 mg Cu, or 200 microg Cr and 3.0 mg Cu/d for
      12 weeks. A significant interactive effect of Cr and Cu supplementation on
      lymphocyte proliferation was observed with ConA 50 microg/ml stimulation. After
      12 weeks of supplementation, ConA-stimulated (50 microg/ml) lymphocyte
      proliferation was significantly lower when Cu was added to the Cr supplementation
      group. Moreover, ConA-stimulated (100 microg/ml) lymphocyte proliferation was
      significantly lower in the Cu supplementation group compared to the Cr
      supplementation group after 12 weeks of supplementation. These results suggest
      that Cu blocks enhancement of lymphocyte proliferation by Cr supplementation and
      that Cu supplementation has potential suppressive effects on the immune function
      in these subjects.

PMID- 11966763
TI  - Expression of eotaxin, an eosinophil-selective chemokine, parallels eosinophil
      accumulation in the vesiculobullous stage of incontinentia pigmenti.
AB  - Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis primarily
      affecting female children. The initial vesiculobullous stage of IP is
      characterized clinically by inflammatory papules, blisters, and pustules, and
      histopathologically by acanthosis, keratinocyte necrosis, epidermal spongiosis
      and massive epidermal eosinophil infiltration. The cause of this multisystem
      disease is attributed to the mutations of an X-linked regulatory gene, termed
      nuclear factor-kappaB essential modulator (NEMO). The exact mechanism of
      epidermal eosinophil accumulation has not yet been determined. We explored the
      possible role of an eosinophil-selective, nuclear factor-kappaB-activated
      chemokine, eotaxin, in the accumulation of eosinophils in the initial stage of
      the disease. Monoclonal antibody (6H9) specific for human eotaxin strongly
      labelled the suprabasal epidermis of IP skin, paralleling the upper epidermal
      accumulation of eosinophils, but did not label the epidermis of normal skin or
      lesional skin from patients with other inflammatory skin diseases not
      characterized by prominent eosinophil accumulation, namely dermatitis
      herpetiformis and selected cases of atopic dermatitis lacking significant numbers
      of eosinophils. In addition, endothelial cells in lesional skin of IP also
      exhibited strong expression of eotaxin, which correlated with perivascular and
      intravascular eosinophil infiltration. We also examined the in vitro effects on
      epidermally derived eotaxin of several cytokines that were nuclear factor-kappaB
      activated and/or known to induce eotaxin expression. In normal human
      keratinocytes, proinflammatory cytokines either independently (IL-1alpha) or
      synergistically (tumour necrosis factor-alpha (TNF-alpha)/ interferon-gamma (IFN
      gamma) and TNF-alpha/IL-4) up-regulated eotaxin expression. These studies suggest
      that release of cytokines during the initial inflammatory stage of IP induces
      epidermal expression of eotaxin, which may play a role in the epidermal
      accumulation of eosinophils.

PMID- 11966764
TI  - Graves' disease is associated with an altered CXCR3 and CCR5 expression in
      thyroid-derived compared to peripheral blood lymphocytes.
AB  - The mechanisms by which T cells accumulate in the thyroid and support the
      autoimmune process in patients with Graves' disease (GD) are poorly understood.
      Chemokines and their receptors may be involved in this process. We have analysed
      the expression of CXCR3 and CCR5 as Th1-specific chemokine receptors, CCR3 as a
      marker for Th2 cells, CXCR4 (expressed on unprimed, naive T cells) and CCR2
      (known to be involved in autoimmunity) on peripheral blood (PBL) and thyroid
      derived lymphocytes (TL) using flow cytometry. Chemokine receptor expression on
      PBL of GD patients (n = 16) did not differ from that of normal controls (n = 10).
      In GD, CXCR3+ (67.3 +/- 4.0% versus 45.7 +/- 2.1%) and CCR5+ T cells (42.5 +/-
      3.4% versus 18.8 +/- 2.1%) showed a significant enrichment in the TL compared to
      PBL. The positive cells were contributed mainly by the CD4+CD45R0+ subset. TL are
      mostly primed CD45R0+ T cells, but surprisingly, they had significantly higher
      levels of CXCR4+ cells among TL (96.2 +/- 1.0%) compared to PBL (66.8 +/- 4.2%).
      However, CXCR4 has been induced during in vitro isolation of TL. There was no
      correlation between chemokine receptors and the level of TSH-receptor and thyroid
      peroxidase autoantibodies. CCR3+ and CCR2+ cells remained unchanged in TL
      compared to PBL. We could confirm the results using RT PCR and immunohistology.
      In summary, TL showed a different chemokine receptor pattern compared to PBL from
      the same patient. This indicates a role for CXCR3 and CCR5 in the recruitment of
      T cells to the thyroid in GD.

PMID- 11966765
TI  - Plasma levels of soluble CD27: a simple marker to monitor immune activation
      during potent antiretroviral therapy in HIV-1-infected subjects.
AB  - Plasma levels of soluble CD27 (sCD27) are elevated in diseases characterized by T
      cell activation and are used as a marker of immune activation. We assessed the
      usefulness of determining plasma sCD27 as a marker for monitoring immune
      activation in HIV-1-infected patients treated with highly active antiretroviral
      therapy (HAART). A first cross-sectional examination of 68 HIV-1-infected and 18
      normal subjects showed high levels of sCD27 in HIV-1 infection; plasma sCD27 was
      correlated to HIV-1 viraemia and inversely correlated to CD4+ T cell count.
      Twenty-six HIV-1-infected patients undergoing HAART were studied at baseline and
      after 6, 12, 18 and 24 months of therapy. Seven additional patients under HAART
      were analysed at baseline, during and after interruption of therapy. In the total
      population, HAART induced a significant and progressive reduction, but not a
      normalization, of plasma levels of sCD27 after 24 months. A full normalization of
      plasma sCD27 was observed in the virological responders (undetectable HIV-1 RNA
      at months 18 and 24) and also in patients with moderate immunodeficiency at
      baseline (CD4+ T cell count >200 cells/mm3). Changes in plasma neopterin
      paralleled the changes in sCD27 but only baseline sCD27 levels were predictive of
      a greater increase in CD4+ T cell count during the follow-up. Discontinuation of
      therapy resulted in a rapid increase of sCD27 plasma levels associated with
      viraemia rebound and drop in CD4+ T cell count. Our findings suggest that plasma
      sCD27 may represent an alternative and simple marker to monitor immune activation
      during potent antiretroviral therapy. HIV-1-induced immune activation can be
      normalized by HAART in successfully treated patients where the disease is not
      advanced.

PMID- 11966766
TI  - T cell responses to vaccines in infants: defective IFNgamma production after oral
      polio vaccination.
AB  - The immaturity of the neonatal immune system is associated with an increased
      susceptibility to infections. Studies in mice indicate that neonatal immune
      responses are biased towards the T helper 2 type, but little is known about
      helper T cell responses in human newborns. In this study, the oral polio vaccine
      was used as a model of early immunization to investigate the capacity of young
      infants to develop cellular immune responses. We show that neonatal immunization
      with oral polio vaccine induces the production of high titres of neutralizing
      antibodies but reduced proliferative and IFNgamma responses to polio antigens
      compared to immune adults. These data suggest that specific strategies will be
      required to immunize newborns against pathogens controlled by Th1 type immune
      responses.

PMID- 11966767
TI  - Proliferation and telomere length in acutely mobilized blood mononuclear cells in
      HIV infected patients.
AB  - The aim of the study was to investigate the mobilization of T cells in response
      to a stressful challenge (adrenalin stimulation), and to access T cells resided
      in the peripheral lymphoid organs in HIV infected patients. Seventeen patients
      and eight HIV seronegative controls received an adrenalin infusion for 1 h. Blood
      was sampled before, during and 1 h after adrenalin infusion. Proliferation and
      mean telomere restriction fragment length (telomeres) of blood mononuclear cells
      (BMNC) and purified CD8+ and CD4+ cells were investigated at all time points. In
      patients, the proliferation to pokeweed mitogens (PWM) was lower and decreased
      more during adrenalin infusion. After adrenalin infusion the proliferation to PWM
      was restored only in the controls. In all subjects telomeres in CD4+ cells
      declined during adrenalin infusion. Additionally, the patients had shortened
      telomeres in their CD8+ cells, and particularly HAART treated patients had
      shortened telomeres in all cell-subtypes. The finding that patients mobilized
      cells with an impaired proliferation to PWM during and after adrenalin infusion
      has possible clinical relevance for HIV infected patients during pathological
      stressful conditions, such as sepsis, surgery and burns. However, this study did
      not find a correlation between impaired proliferation and telomeres. It is
      concluded that physiological stress further aggravates the HIV-induced immune
      deficiency.

PMID- 11966769
TI  - Immune response of the coeliac nasal mucosa to locally-instilled gliadin.
AB  - We previously demonstrated a specific gluten-induced response in the rectal
      mucosa of coeliac patients. In the present study, we have evaluated the immune
      response to local gliadin challenge in the nasal mucosa of coeliac patients
      preliminary to exploring the feasibility of immune modulation by the nasal route.
      The local response to gliadin was evaluated on non-invasive scrapings of nasal
      mucosa. Cells harvested from the nasal scrapings of 21 coeliac patients and 12
      healthy controls were counted after immunohistochemical staining. Six hours after
      gliadin challenge, the total number of cells was increased in coeliacs but not in
      controls. The increase was due principally to lymphoid cells and granulocytes.
      CD3+ cells doubled after gliadin challenge, but not after albumin control
      challenge. There was a similar rise in CD25+ cells, whereas the number of ICAM
      expressing cells did not increase significantly. In control subjects, both
      gliadin and albumin induced a moderate but not significant increase in total cell
      number. In conclusion, the gliadin antigen provokes a mild inflammatory response
      in coeliac nasal mucosa.

PMID- 11966768
TI  - Intracellular cytokine production by Th1/Th2 lymphocytes and monocytes of
      children with symptomatic transient hypogammaglobulinaemia of infancy (THI) and
      selective IgA deficiency (SIgAD).
AB  - Intracellular expression of several cytokines was assessed in lymphocytes and
      monocytes of children with transient hypogammaglobulinaemia of infancy (THI) and
      selective IgA deficiency (SIgAD). THI was characterized by an increased frequency
      of CD3+/CD4+ lymphocytes expressing tumour necrosis factor alpha (TNF-alpha), TNF
      beta and interleukin 10 (IL-10), while in SIgAD elevated numbers of these cells
      containing TNF-alpha and interferon gamma (IFN-gamma) were observed. No changes
      in the number of CD4+ T cells expressing IL-4 in both diseases were noted. The
      proportion of CD33+ monocytes containing TNF-alpha both in THI and SIgAD was
      unchanged. The secretion of IL-12 by peripheral blood mononuclear cells (PBMCs)
      of patients with THI and SIgAD was significantly elevated and associated with an
      increased frequency of IL-12 expressing monocytes in THI but not in SIgAD. IL-18
      secretion was slightly, but not significantly, elevated in both diseases.
      Intracellular Th1 and Th2 type cytokines within CD3+/CD4+ lymphocytes were also
      determined in the normal blood donors that showed high or low production of IgG
      and IgA in vitro. In low producers of IgG an increased proportion of CD3+/CD4+
      cells expressing TNF-alpha and IFN-gamma was found, while in low IgA responders
      only elevated TNF-alpha positive CD3+/CD4+ cells were observed. These results
      suggest that THI and SIgAD may represent diseases with an excessive Th1 type
      response that is associated with an up-regulation of IL-12 secretion and, at
      least in THI, elevated numbers of monocytes expressing intracellular IL-12. Up
      regulation of IL-12 may be the essential factor in the patomechanism(s) of these
      diseases as already described in common variable immunodeficiency (CVID).

PMID- 11966770
TI  - Elevated expression of CCR5 by myeloid (CD11c+) blood dendritic cells in multiple
      sclerosis and acute optic neuritis.
AB  - Myeloid and plasmacytoid dendritic cells (DC) are present in cerebrospinal fluid
      (CSF) in non-inflammatory neurological diseases (NIND) and elevated in clinically
      definite multiple sclerosis (MS) and in early MS - acute monosymptomatic optic
      neuritis (ON). Here, we show that expression of CCR5, a chemokine receptor for
      regulated on activation, normal T cell expressed and secreted (RANTES) and
      macrophage inflammatory protein (MIP)-1alpha/beta, is elevated on blood myeloid
      (CD11c+) DC in MS and ON compared to non-inflammatory controls. In contrast,
      expression of CXCR4, a receptor for stromal cell-derived factor (SDF)-1alpha, is
      similar in all groups. Blood myeloid DC from MS patients respond chemotactically
      to RANTES and MIP-1beta, which are expessed in MS lesions. In active MS and ON,
      expression of CCR5 by myeloid DC in blood correlates with numbers of these cells
      in CSF. Thus, elevation of CCR5 may contribute to recruitment of myeloid DC to
      CSF in MS and ON. Recruitment of plasmacytoid DC to CSF appears to be CCR5
      independent.

PMID- 11966771
TI  - Expression of T cell receptor variable region families by bone marrow gammadelta
      T cells in patients with IgA nephropathy.
AB  - IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA
      (pIgA). Abnormalities of the IgA system include reduced mucosal and increased
      bone marrow (BM) pIgA production. Gammadelta T cells are regulators of mucosal
      IgA production and oral tolerance. We have described previously a deficiency of
      gammadelta T cells expressing Vgamma3 and Vdelta3 from the duodenal mucosa in
      IgAN. Since pIgA production is displaced to the BM, we have now studied BM
      gammadelta T cells in IgAN. Peripheral blood and BM aspirates were obtained from
      14 patients with IgAN and 15 controls. Expression of TCR gamma and delta V region
      families was analysed by semiquantitative RT-PCR, and CDR3 spectratyping of
      Vgamma1-4 and Vdelta3 genes was performed. We found no difference between IgAN
      and controls in the V region usage of blood gammadelta T cells. However, in the
      BM of patients with IgAN, there was significantly reduced expression of the V
      region families Vgamma3 and Vdelta3, with the decrease in Vdelta3 being
      particularly striking. CDR3 spectratyping showed no abnormalities in blood or BM
      samples. Vgamma3 and Vdelta3 are underexpressed in the duodenum and the BM in
      IgAN. The combination of imbalanced mucosal and systemic pIgA production with
      deficient expression of gammadelta T cells using Vgamma3 and Vdelta3 in both
      sites may imply a role for these gammadelta T cells in the normal regulation of
      IgA immune responses, and in the complex immunopathogenesis of IgAN.

PMID- 11966772
TI  - The cytoplasmic linker protein CLIP-170 is a human autoantigen.
AB  - The purpose of this study was to identify autoantigens that are recognized by
      human sera and are associated with a speckled cytoplasmic fluorescent staining
      pattern on tissue culture cells, and to determine clinical features associated
      with specific autoantibodies. A serum from a patient with systemic lupus
      erythematosus was used to identify a 3.7-kb cDNA insert from a HeLa cell
      expression library. The purified cDNA (VLK2.1) encoded a peptide of 1051 amino
      acids that shared 98.4% similarity with the carboxyl terminal portion of a
      previously reported 170 kD protein named cytoplasmic linker protein-170 (CLIP
      170). Antibodies affinity purified with the recombinant CLIP-170 protein, the
      prototype human serum and a monoclonal antibody raised against CLIP-170 exhibited
      identical speckled staining of the cytoplasm in HEp-2 cells. The human
      autoantibodies reacted with the purified recombinant protein in a Western
      immunoblot and immunoprecipitated the in vitro translated recombinant protein.
      Three additional human sera also immunoprecipitated the recombinant CLIP-170
      protein. The clinical diagnoses in these patients were limited scleroderma,
      glioblastoma and idiopathic pleural effusion. This is the first report that
      identifies CLIP-170 as a human autoantigen.

PMID- 11966773
TI  - Expression, modulation and signalling of IL-17 receptor in fibroblast-like
      synoviocytes of patients with rheumatoid arthritis.
AB  - Interleukin-17 (IL-17) has been characterized as a proinflammatory cytokine
      produced by CD4+ CD45RO+ memory T cells. Overproduction of IL-17 was detected in
      the synovium of patients with rheumatoid arthritis (RA) compared to patients with
      osteoarthritis. In contrast to the restricted expression of IL-17, the IL-17
      receptor (IL-17R/CDw217) is expressed ubiquitously. Using a real-time RT-PCR
      assay, we detected similar absolute levels of IL-17R mRNA expression in
      fibroblast-like synoviocytes (SFC) from patients with RA (mean 9 pg/microg total
      RNA; ranged from 0.1 pg to 96 pg IL-17R mRNA/microg total RNA) compared to
      synoviocytes of non-RA patients. Analysis of the IL-17R surface expression
      confirmed the results obtained for IL-17R mRNA expression. Exposure of SFC to IL
      17 led to a mRNA induction of CXC chemokines IL-8, GRO-alpha and GRO-beta. An
      anti-IL-17 antibody blocked these effects of IL-17. The MAPK p38 appears
      necessary for the regulation of IL-8, GRO-alpha and GRO-beta expression as shown
      by inhibition with SB203580. The inhibitors genistein (tyrosine kinase inhibitor)
      and calphostin C (inhibitor of protein kinase C) reduced significantly the IL-17
      stimulated mRNA expression of IL-8, GRO-alpha and GRO-beta in SFC, whereas
      PD98059 (inhibitor of MEK-1/2) was without effect. Pharmacological drugs used in
      therapy of RA, such as cyclosporin and methotrexate, induced a fourfold increase
      of IL-17R mRNA expression and augmented the IL-17-stimulated IL-8 expression. Our
      results support the hypothesis that IL-17/IL-17R may play a significant role in
      the pathogenesis of RA contributing to an unbalanced production of cytokines as
      well as participating in connective tissue remodelling.

PMID- 11966774
TI  - Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF
      beta1 in synovial fibroblasts from rheumatoid arthritis and normal individuals.
AB  - Transforming growth factor (TGF)-beta1 is expressed abundantly in the rheumatoid
      synovium. In this study, the inflammatory effect of TGF-beta1 in rheumatoid
      arthritis (RA) was investigated using cultured fibroblast-like synoviocytes (FLS)
      from RA and osteoarthritis (OA) patients, as well as non-arthritic individuals.
      mRNA expressions of IL-1beta, tumour necrosis factor (TNF)-alpha, IL-8,
      macrophage inflammatory protein (MIP)-1alpha and metalloproteinase (MMP)-1 were
      increased in RA and OA FLS by TGF-beta1 treatment, but not in non-arthritic FLS.
      Enhanced protein expression of IL-1beta, IL-8 and MMP-1 was also observed in RA
      FLS. Moreover, TGF-beta1 showed a synergistic effect in increasing protein
      expression of IL-1beta and matrix metalloproteinase (MMP)-1 with TNFalpha and IL
      1beta, respectively. Biological activity of IL-1 determined by mouse thymocyte
      proliferation assay was also enhanced by 50% in response to TGF-beta1 in the
      culture supernatant of RA FLS. DNA binding activities of nuclear factor (NF)
      kappaB and activator protein (AP)-1 were shown to increase by TGF-beta1 as well.
      These results suggest that TGF-beta1 contributes for the progression of
      inflammation and joint destruction in RA, and this effect is specific for the
      arthritic synovial fibroblasts.

PMID- 11966776
TI  - A tribute to Bernard Amos.

PMID- 11966775
TI  - Antibodies to 70 kD and 90 kD heat shock proteins are associated with graft
      versus-host disease in peripheral blood stem cell transplant recipients.
AB  - The development of graft-versus-host disease (GVHD) can be modified by non-MHC
      factors. Based on our previous studies that showed an involvement of 70kD heat
      shock protein (hsp70) in the pathology of acute GVHD in a rat model, we
      determined serum levels of antibodies to hsp70, hsp90 and hsp60 in human
      recipients after allogeneic peripheral blood stem cell transplantation (PBSCT).
      Serum levels of these antibodies were correlated with GVHD status in the
      recipients. Twenty-nine recipients with high-risk haematological malignances, who
      received G-CSF mobilized allogeneic PBSCT from HLA matched family donors, were
      evaluated between 30 and 960 days after transplantation. Two recipients had no
      GVHD, 18 developed acute followed by chronic GVHD and nine developed only chronic
      GVHD. Patients with acute GVHD had a significant increase in IgM anti-hsp70
      and/or anti-hsp90 early (30-90 days) after transplantation. In addition, an
      increase in IgM anti-hsp70 and/or anti-hsp90 antibodies preceded or accompanied
      chronic GVHD. Antibody levels returned to normal within the next 400 days in the
      majority of patients. Anti-hsp60 antibody levels were not different from control
      levels regardless of GVHD status. This study implies that the development of
      acute and/or chronic GVHD in humans is accompanied by an increase in anti-hsp70
      and anti-hsp90 antibodies. Monitoring levels of anti-hsp70 and anti-hsp90
      antibodies in stem cell transplant recipients may serve as a diagnostic tool and
      help to predict the onset of GVHD.

PMID- 11966777
TI  - Impact of human herpesvirus-6 on the frequency and severity of recurrent
      hepatitis C virus hepatitis in liver transplant recipients.
AB  - A role of tumor necrosis factor-alpha (TNF-alpha) In the immunopathogenesis of
      hepatitis C virus (HCV) infection has been proposed. The novel herpes virus,
      human herpes virus-6 (HHV-6), is amongst the most potent inducers of cytokines,
      including TNF-alpha. The impact of HHV-6 viremia on the progression of recurrent
      HCV hepatitis was assessed in 51 HCV-positive liver transplant recipients. The
      frequency of recurrent HCV hepatitis did not differ between patients with HCV
      viremia (47.6%, 10/21) as compared with those without HCV viremia (46.7%, 14/30,
      p = 0.9). However, the patients with HHV-6 viremia had a significantly higher
      fibrosis score upon HCV recurrence than those without HHV-6 viremia (mean 1.5 vs.
      0.3, p = 0.01). An association between cytomegalovirus (CMV) viremia and HCV
      recurrence was not documented; 50% (15/30) of the patients with CMV viremia and
      42.8% (9/21) of those without CMV viremia had recurrent HCV hepatitis (p > 0.5).
      Receipt of ganciclovir (administered upon the detection of CMV viremia) was
      associated with lower total Knodell score (mean 5.2 vs. 6.9, p = 0.05) and a
      trend towards lower fibrosis score (mean 0.44 vs. 1.00, p = 0.12) in patients
      with recurrent HCV hepatitis. Thus, HHV-6 viremia in HCV-positive liver
      transplant recipients identified a subgroup of patients at increased risk for
      early fibrosis upon HCV recurrence.

PMID- 11966778
TI  - Immunoadsorption of sensitized kidney transplant candidates immediately prior to
      surgery.
AB  - Patients with anti-human leucocyte antigen (HLA) antibodies from previous
      transplantation, blood transfusion are highly sensitized and at risk to
      hyperacute renal graft loss. As these antibodies are identified to be of
      pathogenic importance, an effective removal may allow successful transplantation.
      Six 'high risk patients' [panel-reactive antibodies (PRA) >30% or retransplanted
      patients with an acutely rejected first graft within 6 months from surgery] were
      treated by protein A immunoadsorption (IA) immediately prior to transplantation.
      We treated the calculated plasma volume one to three times prior to surgery: mean
      4600 mL (range 2100-10 200 mL). After transplantation we repeated the sessions
      according to antibody (Ab) recurrence, graft function and signs of rejection. The
      panel reactive Ab were reduced from mean 65% pre-IA (range 35-85) to lowest 15%
      (range 0-55). After the course they reappeared to 30% (range 0-90). Five of the
      six patients had no clinical signs of vascular rejection. At a follow-up of mean
      54 months (+/-14) four grafts still function with a mean serum creatinine of 172
      micromol/L (+/-57). Protein A IA is a safe and effective adjunct in the treatment
      of highly sensitized patients awaiting renal transplantation. The treatment
      immediately prior to operation can prevent hyperacute rejection and increases the
      graft survival in these patients.

PMID- 11966779
TI  - Correlation between optimal tacrolimus doses and the graft weight in living donor
      liver transplantation.
AB  - The optimal doses of tacrolimus (FK) needed to reach and maintain a target blood
      level vary among cases of living donor liver transplantation (LDLT). One hundred
      and twenty four LDLTs in 122 patients were included in this study. Tacrolimus was
      administered by continuous intravenous infusion at a rate of 2.5 microg/kg/h just
      after the operation. The time needed to reach the target blood level and the dose
      needed to maintain this level for 1 week (17-18 ng/mL) were defined as the
      initial duration (ID) and secondary dose (SD), respectively. In the first 100
      LDLTs, the correlations between ID or SD and some clinical factors were examined
      and equations for predicting ID or SD were derived. In the latest 24 LDLTs, FK
      was administered using these equations and the actual and calculated ID and SD
      values were compared. A multiple regression analysis revealed that only the graft
      weight/recipient standard liver volume (GW/SLV) ratio (%) correlated with ID or
      SD. Stepwise regression analysis led to the equations ID (h) = 0.4 x GW/SLV ratio
      + 0.2; SD (microg/kg/h) = 0.02 x GW/SLV ratio - 0.4. Simple regression analysis
      revealed a significant correlation between the actual and calculated ID and SD
      values (p < 0.0001). Initial duration and SD can be estimated from equations
      using the GW/SLV ratio.

PMID- 11966781
TI  - Life satisfaction and adverse effects in renal transplant recipients: a
      longitudinal analysis.
AB  - INTRODUCTION: Previous cross-sectional analyses have identified significant
      associations between quality of life (QOL), comorbidities and adverse effects in
      renal transplant recipients. This report examines the longitudinal relationship
      between adverse effects and QOL, with particular attention to the relative impact
      of adverse effects associated with immunosuppression. METHODS: The Transplant
      Learning Center (TLC) is a program designed to improve QOL and preserve graft
      function in transplant recipients. Self-selected enrollees filled out
      questionnaires at roughly 3-month intervals. Each questionnaire included QOL
      scales developed for the program. Repeated measures multiple regression analysis
      was used to examine the relationship between the QOL scales, comorbidities,
      adverse effects, adjusting for other factors. RESULTS: A total of 4247 TLC
      enrollees were included in the analysis, with a mean time since transplant of 5.1
      yr. Comorbidities and adverse effects were common, with high blood pressure
      reported by 87% of respondents and unusual hair growth reported by 69.6%. In
      bivariate analysis, emotional/psychological problems and headaches had the
      largest impact on QOL. In multivariate analysis, emotional/psychological problems
      decreased sexual interest or ability, and headache had the largest adverse QOL
      effect. CONCLUSIONS: We have identified QOL issues that have been previously
      underemphasized in transplant recipients. These findings open new areas of
      research to further explore and define these issues. They provide new
      opportunities for interventions to address factors adversely impacting QOL and to
      develop strategies to improve QOL in these patients. Clinicians should actively
      solicit information about adverse effects of medications, particularly
      information about sexual and relationship issues, when evaluating renal
      recipients. These issues should be taken into account when making therapeutic
      decisions.

PMID- 11966780
TI  - Significance of serial real-time PCR monitoring of EBV genome load in living
      donor liver transplantation.
AB  - BACKGROUND: Quantitative analysis of the Epstein-Barr virus (EBV) genome has been
      recently reported to be helpful for early identification of EBV viremia which
      could reduce the risk of post-transplantation lymphoproliferative disorder
      (PTLD). AIM: To demonstrate the significance of serial monitoring of EBV genome
      load by real-time quantitative polymerase chain reaction (PCR) after living donor
      liver transplantation. METHODS: From March 1999 to April 2000, the EBV genome
      load in peripheral blood mononuclear cells (PBMNC) was measured serially in a
      total of 15 recipients of living donor liver transplantation (LDLT) who had a
      symptomatic EBV infection. RESULTS: In 15 patients, the mean values of the
      highest EBV DNA levels from the patients who had fever, URS, diarrhea, ascites,
      lymphadenopathy and PTLD were 36 232, 16 040, 15 968, 2485, 336 858 and 60 486
      copies/microg DNA, respectively. Patients were treated by reduction or
      discontinuation of immunosuppressives and/or antiviral agents. The EBV DNA levels
      decreased in all these patients following the recovery from their symptoms. We
      encountered two cases of PTLD during this study period. One of them was referred
      to us after the onset of PTLD and one had been undergoing aggressive
      immunosuppression treatment for severe rejection. Both were successfully treated.
      CONCLUSIONS: Serial quantitative analysis of the EBV genome load by means of real
      time PCR are thought to be useful for preventing PTLD through adjustment of the
      immunosuppression level in response to the viral genome load following
      symptomatic EBV infection.

PMID- 11966782
TI  - Impact of HLA-compatibilities in patients undergoing liver transplantation for
      HBV-cirrhosis.
AB  - Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV)
      infection is frequently complicated by HBV recurrence. In the present study we
      investigated whether human leucocyte antigen (HLA)-matching influences the
      outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver
      transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after
      OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months).
      Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction
      therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis
      B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5
      yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B
      recurrence was responsible for 15 of 20 (75%) graft failures. We observed a
      significantly improved graft survival in patients with more HLA-A, -B
      compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not
      influence the outcome. The occurrence of HBV-reinfection was significantly lower
      in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was
      prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when
      compared with patients with HBV-reinfection and a complete HLA-B mismatch (p =
      0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B
      compatibilities seems to be associated with an improved graft survival in
      patients after OLT for end-stage HBV infection.

PMID- 11966783
TI  - Impact of hepatitis B and C on graft loss and mortality of patients after kidney
      transplantation.
AB  - BACKGROUND: Mortality or graft loss after renal transplantation might be
      influenced by hepatitis virus infection. METHODS: Sera from time of
      transplantation of 927 renal transplant recipients were tested for hepatitis C
      (HCV) and hepatitis B virus (HBV) in order to investigate the impact of hepatitis
      virus infection on graft loss and mortality over an observation period of 20 yr.
      RESULTS: One hundred and twenty three of 927 patients were HCV positive, 30
      patients HBV positive and seven patients HBV and HCV positive. The observation
      period was 9.2 +/- 4.4 yr. Mortality was significantly higher in patients with
      hepatitis B (p = 0.0005), as well as in patients with concomitant B and C
      hepatitis (p < 0.0001) and in those who acquired HCV infection after
      transplantation (n = 30, p = 0.0192) compared with non-infected patients.
      Patients with replicating HBV infection (HBeAg positive) had the worst prognosis
      (p < 0.0001). In the multivariate analysis the presence of HBeAg (p < 0.0001),
      patients' age (p < 0.0001) and HCV infection after transplantation (p = 0.0453)
      were predictors for death. Graft survival was significantly shorter in patients
      with concomitant hepatitis B and C (p = 0.0087) as well as in HBeAg positive
      patients (p = 0.002). HCV infection or HBs antigenemia did not have a significant
      impact on graft survival compared with non-infected patients. CONCLUSION: HCV
      infection after transplantation is associated with a high mortality whereas
      chronic HCV infection before trans plantation does not have a significant impact
      on mortality. Patients with replicating HBV infection or concomitant HBV and HCV
      infection have a high risk of graft loss and mortality.

PMID- 11966784
TI  - Regular physical exercise improves endothelial function in heart transplant
      recipients.
AB  - BACKGROUND: Impaired endothelial function is detectable in heart transplant (HTX)
      recipients and regarded as risk factor for coronary artery disease. We have
      studied whether endothelial function can be improved in HTX patients
      participating in a regular physical training program as demonstrated in patients
      with chronic heart failure, hypertension and coronary artery disease. METHODS:
      Male HTX patients and healthy, age-matched controls were studied. Seven HTX
      patients (age: 60 +/- 6 yr; 6 +/- 2 yr of HTX) participated in an outpatient
      training program, six HTX patients (age: 63 +/- 8 yr; 7 +/- 1 yr of HTX)
      maintained a sedentary lifestyle without regular physical exercise since
      transplantation. A healthy control group comprised six subjects (age: 62 +/- 6
      yr). Vascular function was assessed by flow-mediated dilation of the brachial
      artery (FMD). Systemic haemodynamic responses to intravenous infusion of the
      endothelium independent vasodilator sodium nitroprusside (SNP) and to NG
      monomethyl-L-arginine (L-NMMA), an inhibitor of constitutive nitric oxide
      synthase, were also measured. RESULTS: Resting heart rate was significantly lower
      (p < 0.05) in healthy controls (66 +/- 13) than in the HTX training group (83 +/-
      11) and in non-training HTX patients (91 +/- 9), baseline blood pressure also
      tended to be lower in healthy subjects and in the training HTX patients. FMD was
      significantly higher (p < 0.05) in the control group (8.4 +/- 2.2%) and in the
      training group (7.1 +/- 2.4%), compared with non-training HTX patients (1.4 +/-
      0.8%). The response of systolic blood pressure (p = 0.08) and heart rate (p <
      0.05) to L-NMMA was reduced in sedentary HTX patients compared with healthy
      controls and heart rate response to SNP was also impaired in sedentary HTX
      patients. DISCUSSION: Regular aerobic physical training restores vascular
      function in HTX patients, who are at considerable risk for developing vascular
      complications. This effect is demonstrable in conduit and systemic resistance
      arteries.

PMID- 11966785
TI  - Immunosuppression for delayed or slow graft function in primary cadaveric renal
      transplantation: use of low dose tacrolimus therapy with post-operative
      administration of anti-CD25 monoclonal antibody.
AB  - BACKGROUND: Patients who develop delayed graft function (DGF) following cadaveric
      renal transplantation have inferior survival to those who do not. Calcineurin
      inhibitors (CNI) may prolong recovery from DGF. Patients with DGF are therefore
      routinely treated with either polyclonal antilymphocyte preparations or
      monoclonal anti-CD3 monoclonal antibodies and delayed introduction of CNI. The
      purpose of this study was to evaluate the efficacy of the anti-CD25 monoclonal
      antibody basiliximab (BSLIX) started post-operatively in patients at high risk
      for DGF combined with low dose tacrolimus (TAC). METHODS: Patients who received a
      primary cadaveric renal transplant only after August 1998 were included in this
      retrospective study (n = 143). All patients received TAC and mycophenolate
      Mofetil (MMF) pre-operatively. At 6 h post-operatively, graft function was
      assessed clinically by urine output and serum creatinine. Those patients who had
      a urine output < 300 cc/6 h or a rising serum creatinine were presumed to be at
      risk for DGF (n = 46). These patients were treated with 20 mg BSLIX and had TAC
      dose reduced to maintain a trough blood level of < 5 ng/mL. Basiliximab was
      repeated at day 5. Patients not felt to be at risk for DGF were treated with
      standard TAC dose with trough level target of 9-12 ng/mL. Patients at risk were
      classified as DGF if they needed dialysis or as slow graft function (SGF) if they
      did not. The combined group (SGF/DGF) were analysed together. Patients with
      SGF/DGF had their TAC dose increased to achieve trough levels of 9-12 ng/mL when
      renal function improved. Patient groups were compared for demographics, need for
      dialysis, serum creatinine, glomerular filtration rate (GFR), TAC trough levels,
      MMF dosage, complications and 1- and 2-yr actuarial graft survival. RESULTS:
      Patients with SGF/DGF had a longer length of stay (8 vs. 5.7 d), were more likely
      to be black (41.3 vs. 25.7%), and required more post-operative haemodialysis (HD)
      (52.2 vs. 4.1%). SGF/DGF and non-SGF/DGF patients had similar rates of rejection
      (28.2 vs. 19.6%, p = 0.28) and steroid resistant rejection (SRR) (6.5 vs. 2.1%, p
      = 0.32). There were no differences in the rate of cytomegalovirus (CMV) infection
      (4.3 vs. 6.1%). Serum creatinine was higher and GFR lower at all time points in
      the SGF/DGF patients. The 1 and 2 yr actuarial survival in the non-SGF/DGF
      patients was 97.6 and 97.6% compared with 1 and 2 yrs actuarial survival of 94.1%
      and 80.0% in the SGF/DGF patients, p = 0.04. There were no differences in patient
      survival. There were no differences in actuarial survival for the SGF/DGF
      patients who received dialysis compared with those who did not receive dialysis.
      Comparison of patients who received HD (n = 28) to those who did not (n = 115),
      regardless of group demonstrated no difference in 1 and 2 yrs actuarial survival,
      100 and 94.1% in HD patients vs. 98.2 and 92.5% in non-HD patients. CONCLUSIONS:
      The clinical diagnosis of SGF/DGF can be made 6 h post-operatively based on urine
      output and serum creatinine. Basiliximab can be started post-operatively in these
      patients and decreased levels of TAC can be used to achieve acceptably low rates
      of rejection in these patients. However, SGF/DGF patients, regardless of their
      need for dialysis, have worse function at 1 yr and lower 2-yr actuarial graft
      survival compared with non-SGF/DGF patients. Most of the poor survival can be
      attributed to the SGF group. Further strategies to either prevent SGF/DGF or to
      optimize treatment in these patients are needed.

PMID- 11966786
TI  - The effect of a mucopolysaccharide-cartilage complex healing ointment on Er:YAG
      laser resurfaced facial skin.
AB  - BACKGROUND: There are several types of dressings which may be utilized after
      facial laser resurfacing. Laser surgeons favoring the open type of dressing have
      used the Aquaphor original formula to reduce the loss of moisture from laser
      resurfaced skin. The objective of this study was to compare the effectiveness of
      a mucopolysaccharide-cartilage complex (MCC) containing healing ointment with the
      standard therapy of Aquaphor ointment in treating erythema, edema, and skin
      erosion caused by Er:YAG laser resurfacing of facial skin. OBJECTIVE: To compare
      healing time after Er:YAG laser resurfacing treated side-by-side with MCC as
      compared with Aquaphor. METHODS: Nineteen patients completing Er:YAG laser
      resurfacing were randomly assigned to receive MCC healing ointment on one side of
      their face and standard therapy with Aquaphor on the other for eight consecutive
      treatment days. Immediately after surgery and again on days 1, 2, 3, 4, 7, and 8,
      the severity of erythema, edema, and erosion was scored on a 0-3 scale (0 = no
      observable effect, 1 = mild, 2 = moderate, 3 = severe). Photographs were taken at
      each follow-up visit. Following scoring on study day 0, the day of resurfacing,
      treatment was applied according to the left or right assignment code of the
      randomization schedule. RESULTS: Mean severity ratings for all variables
      (erythema, edema, and erosion) were consistently lower for MCC healing ointment
      as compared to Aquaphor ointment. Based on the calculated overall efficacy index,
      MCC ointment was statistically superior to Aquaphor for all three variables:
      erythema, P <.001; edema, P =.017; erosion, P <.001. CONCLUSION: The results of
      our study demonstrate that MCC healing ointment may provide an advantage over the
      standard therapy of Aquaphor ointment in the treatment of edema, erosion, and
      erythema caused by laser resurfacing of facial skin. Mean daily severity scores
      were consistently lower and improvement tended to occur earlier with MCC healing
      ointment.

PMID- 11966787
TI  - Treatment of port-wine stain birthmarks using the 1.5-msec pulsed dye laser at
      high fluences in conjunction with cryogen spray cooling.
AB  - BACKGROUND: The majority of port-wine stain (PWS) patients treated with the
      pulsed dye laser (PDL) do not achieve complete blanching. Safe administration of
      higher fluences has been proposed as a means of improving treatment efficacy.
      OBJECTIVE: To determine the safety and efficacy of PWS treatment with the 1.5
      msec PDL at high fluences in conjunction with cryogen spray cooling. METHODS:
      Twenty PWS patients were treated with the PDL in combination with cryogen spray
      cooling utilizing a 7 or 10 mm spot size and fluences ranging from 6 to 15 J/cm2.
      Before and after treatment photographs were compared on a blinded basis. RESULTS:
      No scarring or skin textural changes occurred. Blanching scores were as follows:
      20% of patients achieved 75% or greater blanching after an average of 3.3
      treatments, 30% achieved 50-74% blanching, 20% achieved 25-49% blanching, and 30%
      achieved less than 25% blanching. CONCLUSION: In conjunction with cryogen spray
      cooling, the PDL can be safely used at high fluences. At this time it is not
      clear that the use of higher fluences improves treatment efficacy; however, as
      other aspects of PWS laser treatment are optimized, safe administration of higher
      fluences is likely to be advantageous.

PMID- 11966788
TI  - Gastrin-releasing peptide, a bombesin-like neuropeptide, promotes cutaneous wound
      healing.
AB  - BACKGROUND: Little is known about the effects of neuropeptides on wound healing.
      OBJECTIVE: To investigate the effect of gastrin-releasing peptide (GRP), one of
      the bombesin-like neuropeptides, on wound healing. METHODS: The effects of GRP on
      cultured keratinocyte proliferation and migration were measured by BrdU uptake
      and in vitro scratch assay, respectively. Various concentrations of GRP ointments
      (0, 10(-9), 10(-8), 10(-7), 10(-6) M) were topically applied to 1.0 mm wounds on
      porcine flanks. RESULTS: GRP stimulated keratinocyte growth and locomotion in a
      dose-dependent manner. Topical administration of GRP accelerated macroscopic
      epidermal regeneration in a dose-dependent manner, as measured by planimetry.
      Histologic studies also showed that GRP promoted reepithelialization, including
      epidermal thickness as well as superficial skin coverage. CONCLUSION: Topical use
      of GRP may clinically accelerate wound healing of burns, injuries, chronic
      ulcers, and skin graft donor sites through the enhancement of keratinocyte growth
      and spreading.

PMID- 11966789
TI  - Local anesthesia in hair transplantation.
AB  - BACKGROUND: Safe and effective use of local anesthesia is essential in hair
      transplantation. OBJECTIVE: To review the agents and techniques of local
      anesthesia as applied to hair transplantation. METHODS: Information was retrieved
      from texts, journal articles found by MEDLINE searches, and related references.
      RESULTS: Agents, vasoconstrictors, maximum dosages, toxicity, and techniques are
      discussed. CONCLUSION: Effective local anesthesia can be maintained throughout
      hair transplantation. Care must be exercised to minimize discomfort through
      proper technique and to minimize toxicity through judicious use of
      vasoconstrictors and nerve blocks and by monitoring total dosage. Constant
      monitoring for toxicity is required, as is early intervention in the unlikely
      event that warning signs should appear.

PMID- 11966790
TI  - Surgical rosacea.
AB  - BACKGROUND: Rosacea is a common cutaneous disease. The dermatologic surgeon will
      frequently encounter rosacea in the surgical patient. OBJECTIVE: To describe
      observations regarding surgical and wound care techniques that facilitate and
      improve outcomes in the rosacea patient. METHODS: We present a compilation of our
      clinical experience and observations regarding rosacea in the dermatologic
      surgery. CONCLUSION: Simple interventions such as disease recognition and
      treatment, proper wound care and suture selection, as well as patient counseling
      have proven beneficial in optimizing surgical outcomes in the rosacea patient.

PMID- 11966791
TI  - Valacyclovir prophylaxis for herpes simplex virus infection or infection
      recurrence following laser skin resurfacing.
AB  - BACKGROUND: The CO2 laser for cutaneous resurfacing has been associated with the
      reactivation of herpes simplex virus (HSV), causing delayed reepithelialization
      and scarring. Antiviral agents appear to be effective in reducing reactivation,
      however, the optimal therapeutic regimen has yet to be clearly defined.
      OBJECTIVE: To assess the reactivation rates of HSV after CO2 laser resurfacing in
      patients who received prophylactic valacyclovir for either 10 or 14 days.
      METHODS: One hundred twenty patients received valacyclovir 500 mg twice a day for
      either 10 or 14 days starting the day prior to facial laser resurfacing. Serology
      levels and consecutive Tzank preparations were obtained to determine past
      exposure to HSV and the presence of virus. RESULTS: No patients in either group
      developed an HSV infection or had a recurrence. CONCLUSION: These results support
      the use of valacyclovir in a 10- or 14-day regimen as a preventive agent against
      HSV outbreaks following facial laser resurfacing.

PMID- 11966792
TI  - The use of the spanning suspension suture in facial reconstruction.
AB  - BACKGROUND: The closure of large cutaneous defects of the upper face can be
      challenging, often requiring the use of large rotation, advancement, or
      transposition flaps or skin grafts. OBJECTIVE: To describe the use of the
      spanning suspension suture, a technique we have adapted to facilitate closure of
      large cutaneous defects of the upper face. METHODS: Report of an illustrated
      case. RESULTS: A large full-thickness defect of the temple was successfully
      reconstructed using the spanning suspension suture. CONCLUSION: Use of the
      spanning suspension suture permits recruitment of skin from the lower cheek and
      neck in the closure of large wounds of the upper face, avoiding the need for
      transposition or rotation flaps and grafts.

PMID- 11966793
TI  - Human cadaveric allograft for repair of nasal defects after extirpation of Basal
      cell carcinoma by Mohs micrographic surgery.
AB  - BACKGROUND: Immediate reconstruction after removal of skin cancer by Mohs
      micrographic surgery (MMS) may not be feasible in patients unwilling or unable to
      undergo an extensive procedure. Human cadaveric allograft (HCA) may offer a
      useful alternative to granulation. OBJECTIVE: To examine the usefulness of HCA in
      resurfacing nasal defects after extirpation of basal cell carcinoma (BCC) by MMS.
      METHODS: Case histories of seven patients treated with HCA were reviewed with
      respect to primary skin cancer histology, defect size, medical status, healing
      time, and cosmesis. RESULTS: Five of seven tumors were infiltrative BCCs. Defects
      ranged from 2.7 to 20 cm2. Average healing times for wounds with and without
      exposed cartilage were 42 and 35 days, respectively. There were no wound
      infections. Hypergranulation tissue was noted in three patients and had no effect
      on cosmesis, which was adequate in five patients and poor in two patients.
      CONCLUSION: HCA may be a useful alternative to granulation following MMS for
      treatment of skin cancers involving the nose.

PMID- 11966794
TI  - Treatment of a large superficial basal cell carcinoma with 5% imiquimod: a case
      report and review of the literature.
AB  - BACKGROUND: Large superficial basal cell carcinomas (BCCs) may be difficult to
      treat surgically due to the potentially large resulting defect after removal.
      Imiquimod, an immune response modifier, when applied topically, has been
      demonstrated to be successful in treating superficial BCCs. There is no published
      experience on the treatment of larger superficial BCCs (greater than 2 cms2) with
      imiquimod at this time. OBJECTIVE: To assess the clinical and histologic
      regression, as well as the short- and long-term effects of topical imiquimod on
      large superficial BCC. METHOD: A 52-year-old white female with a 30 cm2 biopsy
      proven superficial BCC of 28 years duration on the right dorsal arm was treated
      with 5% imiquimod three times a week for 12 weeks. Clinical follow-up was
      conducted 1, 4, 6, and 10 months after treatment, as well as histologic
      assessment of recurrence at 4 months after treatment. RESULTS: Apparent clinical
      and histologic clearance was achieved. The treatment was well-tolerated and the
      patient completed the treatment schedule without a rest period, despite erosion
      of the lesion in the last week of treatment. CONCLUSION: This report describes
      the first case of a large superficial BCC (30 cm2) successfully treated with
      topical imiquimod and with a 10 month follow-up.

PMID- 11966795
TI  - Surgical management of rhinophyma: report of eight patients treated with
      electrosection.
AB  - BACKGROUND: Rhinophyma is the end stage of rosacea, affecting almost exclusively
      male patients, characterized by a progressive deformity in nasal shape. Depending
      on the extent of the deformity, rhinophyma may distort the appearance of those
      affected and patients may become psychosocially disabled. OBJECTIVE: To present
      the results of electrosurgical technique of sequential delamination with a
      slightly damped current in rhinophyma. METHODS: Eight healthy male patients
      affected by moderate to severe rhinophyma were recruited. A radiofrequency
      electrosurgical unit was used in the cut/coagulate mode at 40 W (3.8 MHz) to
      remove thin layers of tissue until the nose shape was re-created. RESULTS: All
      patients achieved acceptable cosmetic results. Cutaneous reepithelialization was
      achieved at day 14 after surgery. Erythema subsided within 4-8 weeks and healing
      was complete with minimal scar formation by 8-10 weeks. None of the patients
      developed hypertrophic scarring and hypopigmentation was minimal. CONCLUSION:
      Electrosection is as effective as laser treatments and less expensive. Although
      living in a laser era, electrosurgical remodeling of the nose is a good
      alternative for the treatment of rhinophyma.

PMID- 11966796
TI  - Treatment of anogenital warts by pulsed dye laser.
AB  - BACKGROUND: Treatment of anogenital warts is difficult in that the disease
      spectrum is wide. Moreover, varying degrees of improvement are obtained.
      OBJECTIVE: To study the treatment of persistent anogenital warts by pulsed dye
      laser. METHODS: Pulsed dye laser was used with the following settings: spot size
      7 mm, pulse duration 1500 microsec, and fluence 7.5 J/cm2. Two different
      wavelengths were used: 585 and 595 nm. RESULTS: Lesions healed completely using
      both wavelengths after one treatment. CONCLUSION: Pulsed dye laser has been found
      to be safe, effective, satisfactory, and less traumatic compared to other options
      for treatment of perianal warts in children.

PMID- 11966797
TI  - Cervicomental "turkey gobbler": a new source for full-thickness grafts.

PMID- 11966798
TI  - The surgical looking glass: a readily available safeguard against eye splash
      injury/contamination during infiltration of anesthesia for cysts and other
      "porous" lesions of the skin.
AB  - BACKGROUND: "Breaks" in barrier precautions are a definite abrogating influence
      on the effectiveness of "universal precautions." Dermatologists and dermatologic
      surgeons are exposed to significant infectious agents on a daily basis,
      especially due to the high number of minor surgical procedures performed.
      Backsplash, spray, and eye splash of bodily fluids during these procedures place
      the surgeon at a high risk of contamination/infection via the conjunctival
      membranes. The surgical looking glass is a simple utility based on inexpensive
      equipment already in place in the physician's office which protects the eyes and
      face during infiltrative anesthesia or incision of cysts and other lesions.
      OBJECTIVE: To offer a simple and inexpensive utility to assist with protection
      from and reduction of contamination/infection of the ocular mucous membranes
      during surgical procedures. METHODS: Utilizing one or two readily available
      microscope slides overlying the injection site during local infiltrative
      anesthesia, backsplash or spray can be contained. RESULTS: This utility is
      effective in containment of backsplash or spray of anesthesia or bodily fluids
      during even minor surgical procedures. CONCLUSION: The surgical looking glass can
      enhance safety and promote "universal precautions" during even minor surgical
      procedures or infiltration of anesthesia into more porous areas or lesions for
      the practicing dermatologist or dermatologic surgeon. The pragmatic, practical,
      and inexpensive nature of the surgical looking glass invites its use on a daily
      basis by the practicing dermatologist.

PMID- 11966799
TI  - Temporal artery biopsy site.

PMID- 11966800
TI  - Human antihyaluronic acid antibodies.

PMID- 11966801
TI  - Scarring alopecia: case study.

PMID- 11966802
TI  - Doppler commentary.

PMID- 11966803
TI  - Commentary on lower lip reconstruction.

PMID- 11966804
TI  - Bulky centrally monopedicled vs. flat obliquely bipedicled island flaps.

PMID- 11966805
TI  - Use of insulating sleeve during electrosurgery.

PMID- 11966808
TI  - Think big: the international dimension of environmental microbiology.

PMID- 11966809
TI  - The expanding interdisciplinary nature of environmental microbiology.

PMID- 11966810
TI  - A need to retrieve the not-yet-cultured majority.

PMID- 11966811
TI  - Crystal ball look to the future.

PMID- 11966812
TI  - Re-birth of microbial physiology.

PMID- 11966813
TI  - Towards the end of experimental (micro)biology?

PMID- 11966814
TI  - Towards microbial systems science: integrating microbial perspective, from
      genomes to biomes.

PMID- 11966815
TI  - Diversity squared.

PMID- 11966816
TI  - New unity, new opportunities.

PMID- 11966817
TI  - Expanding the map of microbial metabolism.

PMID- 11966818
TI  - Microbial community analysis.

PMID- 11966819
TI  - The future for culturing environmental organisms: a golden era ahead?

PMID- 11966820
TI  - Anaerobic eukaryotes and their archaebacterial endosymbionts.

PMID- 11966821
TI  - Microbial imprints as forensic tools in food production.

PMID- 11966822
TI  - The regulation of biofilm development by quorum sensing in Aeromonas hydrophila.
AB  - Aeromonas hydrophila is an opportunistic Gram-negative pathogen that readily
      attaches to stainless steel to produce a thin biofilm with a complex 3D structure
      covering 40-50% of the available surface and producing large microcolonies. As A.
      hydrophila possesses an N-acylhomoserine lactone (AHL)-dependent quorum-sensing
      system based on the ahyRI locus, the presence of the AhyI protein and C4-HSL
      within the biofilm phase was first established by Western blot and AHL biosensor
      analysis respectively. The ability of the A. hydrophila AH-1 N strain to form
      biofilms in a continuous-flow chamber was compared with isogenic ahyI and ahyR
      mutants. The ahyI mutant, which cannot produce C4-HSL, failed to form a mature
      biofilm. In addition, the viable count of biofilm, but not planktonic phase ahyI
      mutants, was significantly lower that the parent or ahyR mutant. This defect in
      the differentiation of the ahyI mutant biofilm could be partially restored by the
      addition of exogenous C4-HSL. A mutation in ahyR increased coverage of the
      available surface to around 80% with no obvious effect upon biofilm microcolony
      formation. These data support a role for AHL-dependent quorum sensing in A.
      hydrophila biofilm development. Exposure of the A. hydrophila AH-1N biofilm to N
      (3-oxodecanoyl)homoserine lactone, which inhibits exoprotease production in
      planktonic cells, however, had no effect on biofilm formation or architecture
      within the continuous-flow chamber.

PMID- 11966823
TI  - Deciphering the action of aromatic effectors on the prokaryotic enhancer-binding
      protein XylR: a structural model of its N-terminal domain.
AB  - The prokaryotic enhancer-binding protein XylR is the central regulator of the
      toluene degradation pathway in Pseudomonas species. Copious genetic and
      biochemical data indicate that the N-terminal domain of the protein (domain A)
      interacts directly with m-xylene, which renders the protein competent as a
      transcriptional activator. Single-site and shuffling mutants of XylR or
      homologues have been reported to change or expand their effector profiles. Here,
      we follow a fold recognition approach to generate three-dimensional models of the
      domain A of XylR and DmpR with the purpose of deciphering the molecular activity
      of this protein family. The model is based on the crystallographic data of the
      rat catechol O-methyltransferase, a typical alpha/beta fold, consisting of eight
      alpha-helices and seven beta-strands. The fold identification is supported by
      physico-chemical properties of conserved amino acids, distribution of residues
      characteristic of the sequence families and confrontation with experimental data.
      The model not only provides a rationale for understanding published experimental
      data, but also suggests the molecular mechanism of the activation step and is a
      potentially useful conceptual tool for designing regulators with predefined
      inducer specificities.

PMID- 11966825
TI  - Reduction of humic substances by halorespiring, sulphate-reducing and
      methanogenic microorganisms.
AB  - Physiologically distinct anaerobic microorganisms were explored for their ability
      to oxidize different substrates with humic acids or the humic analogue,
      anthraquinone-2,6-disulphonate (AQDS), as a terminal electron acceptor. Most of
      the microorganisms evaluated including, for example, the halorespiring bacterium,
      Desulfitobacterium PCE1, the sulphate-reducing bacterium, Desulfovibrio G11 and
      the methanogenic archaeon, Methanospirillum hungatei JF1, could oxidize hydrogen
      linked to the reduction of humic acids or AQDS. Desulfitobacterium dehalogenans
      and Desulfitobacterium PCE1 could also convert lactate to acetate linked to the
      reduction of humic substances. Humus served as a terminal electron acceptor
      supporting growth of Desulfitobacterium species, which may explain the recovery
      of these microorganisms from organic rich environments in which the presence of
      chlorinated pollutants or sulphite is not expected. The results suggest that the
      ubiquity of humus reduction found in many different environments may be as a
      result of the increasing number of anaerobic microorganisms, which are known to
      be able to reduce humic substances.

PMID- 11966824
TI  - Prevalence and microdiversity of Alteromonas macleodii-like microorganisms in
      different oceanic regions.
AB  - The presence, prevalence and variability of microorganisms related to the species
      Alteromonas macleodii, a well known culturable gamma-Proteobacterium, has been
      studied in different seawater samples from diverse geographical locations, in
      both the Northern and Southern hemispheres, and tested with two molecular
      techniques (rRNA hybridization and gene cloning and sequencing). Results show
      that A. macleodii-like microorganisms are present in high proportions in North
      Atlantic and, especially, Mediterranean waters, being higher at deep samples and
      particle-associated fractions, in agreement with previous findings. In contrast,
      Southern samples (all from very cold areas near Antarctica) presented no
      significant hybridization signals. The analysis of the ribosomal ITS (16S-23S
      internal transcribed spacers) revealed that A. macleodii-like microorganisms from
      Mediterranean, North Atlantic, Caribbean and Red Sea waters differed in both size
      and sequence, mostly depending on their geographical origin, with Mediterranean
      and North Atlantic clones clustering into two main groups whereas Caribbean and
      Red Sea clones appeared separated.

PMID- 11966826
TI  - Carbon isotopic fractionations associated with thermophilic bacteria Thermotoga
      maritima and Persephonella marina.
AB  - Stable carbon isotopes can provide insight into carbon cycling pathways in
      natural environments. We examined carbon isotope fractionations associated with a
      hyperthermophilic fermentative bacterium, Thermotoga maritima, and a thermophilic
      chemolithoautotrophic bacterium Persephonella marina. In T. maritima,
      phospholipid fatty acids (PLFA) are slightly enriched in 13C relative to biomass
      (epsilon = 0.1-0.8 per thousand). However, PLFA and biomass are depleted in 13C
      relative to the substrate glucose by approximately 8 per thousand. In P. marina,
      PLFA are 1.8-14.5 per thousand enriched in 13C relative to biomass, which
      suggests that the reversed tricarboxylic acid (TCA) cycle or the 3
      hydroxypropionate pathway may be used for CO2 fixation. This is supported by
      small fractionation between biomass and CO2 (epsilon = -3.8 per thousand to -5.0
      per thousand), which is similar to fractionations reported for other organisms
      using similar CO2 fixation pathways. Identification of the exact pathway will
      require biochemical assay for specific enzymes associated with the reversed TCA
      cycle or the 3-hydroxypropionate pathway.

PMID- 11966830
TI  - Psychological distress of cancer and clinical trial participation: a review of
      the literature.
AB  - The House of Commons Select Committee on Science and Technology 2000 state that
      currently less than 5% of adult patients with solid tumours are entered into
      clinical trials. They recommend that increasing the number of adult cancer
      patients entering clinical trials must become a high priority. Health-care
      providers need to prepare themselves for this proposed increase in trial
      participants by assessing the current status of care and implementing changes
      within the current infrastructure to provide optimal holistic care. Cancer can
      change a patient's life either for better or for worse. At one extreme, having
      cancer leads to enhanced appreciation of life and closer bonds with others.
      However, at the other extreme, cancer combined with its treatment is viewed as an
      event that evokes distress and emotional anguish taxing the individual's ability
      to cope. In the last 25 years, owing to the advent of clinical trials, progress
      has been made in cancer treatment. Clinical trials may be hailed as the saviour
      to many therapeutic dilemmas. Treatments are now available which can offer
      patients hope of cure. Nevertheless, many participants may fear, for the purpose
      of research, that they may be assigned to less than optimal therapy or that their
      care will be carried out in a sterile scientific atmosphere devoid of humane and
      personal consideration. These and other reasons may cause unacceptable personal
      distress that overrides the potential therapeutic gain. Cancer diagnosis coupled
      with the ramifications of clinical trial involvement can have significant
      psychological implications. They may trigger the onset of a mood disorder or
      exacerbate a present symptom. This article will identify mood disorders in the
      cancer population, focus on the participants' needs in the clinical trial arena
      and investigate the influence trial participation has on psychological status.

PMID- 11966831
TI  - Incidence and tumour stages of breast cancer in the region of Aachen, Germany.
AB  - We present epidemiological data of female breast cancer in the region of Aachen
      (Germany) including incidence and tumour stages for the period 1996-1997.
      Furthermore, we compare epidemiological data from Aachen with data from the
      directly neighbouring Dutch region South-Middle Limburg before and after the
      introduction of a national mammographic screening programme. The field study of
      breast cancer was undertaken at the Institute of Pathology and Comprehensive
      Cancer Center at the University of Aachen, supported by the Federal Ministry of
      Health (Germany), using data files from the Cancer Registry Aachen. The patient's
      consent to collect all data concerning her epidemiological and social situation
      as well as information on the outcome of disease was obtained in 83.4% of all
      cases. The remaining 16.6% of the cases without a patient's consent are based on
      histopathological reports. Only those patients are included who were documented
      as residing in the region of Aachen at the time of diagnosis. Tumour cases were
      counted according to International Agency for Research on Cancer rules and tumour
      stages are classified according to UICC guidelines. Incidence rates are
      calculated as crude value, adapted to the European and World Standard population
      (ESR, WSR), and the age specific incidence is presented in 5-year intervals. The
      cumulative risk is assessed for a certain life span by summarizing the age
      specific incidences. The age-standardized breast cancer incidence rate in Aachen
      was 94 per 100 000 women in 1996 and 90 cases of invasive breast cancer per 100
      000 women in 1997 according to the ESR. The cumulative risk of developing breast
      cancer in the life span ranging from 0 to 74 years is approximately 8%. The stage
      distribution of breast cancer reveals only 4% favourable carcinomata in situ, but
      12% advanced T4 tumours. T1 and T2 tumour stages count for about 40% and T3
      tumour stages about 4%. Incidence rates and the tumour stages of breast cancer in
      the region of Aachen during 1996 and 1997 are similar to the data obtained from
      the directly neighbouring Cancer Center of the region South-Middle Limburg, in
      the Netherlands, in 1989/1990 before the beginning of the national breast cancer
      screening programme. However, major differences are found in terms of the
      incidence and the tumour stages between Aachen 1996/1997 and South-Middle Limburg
      1995/1996 after the introduction of the mammographic screening. The incidence of
      female breast cancer in Aachen, Germany, was high and in the range of the data
      from other cancer registries in Europe without national screening programmes. The
      tumour stages at diagnosis in Aachen were not very favourable, especially in
      elderly women. An increase of the cancer incidence and a shift of the tumour
      stages to more favourable ones were observed in the neighbouring Dutch region of
      South-Middle Limburg, comparing data from 1989/90 and 1995/96. This is probably
      as a result of the national mammographic screening programme. As data from Aachen
      were similar to Limburg's data from 1989/90 before the mammographic screening was
      introduced, it will be important to follow and compare the cancer incidence and
      the tumour stages in the future.

PMID- 11966832
TI  - Informing the public about advances in cancer therapy.
AB  - The word cancer continues to be associated with fear and pessimism among the
      general public, but they also hear of "new breakthroughs" in the field of
      oncology. This paper considers whether or not such research advances in cancer
      are occurring and, if so, is this information being accurately transmitted both
      within and outside the medical profession. If information is to be given to the
      public, what preparatory work needs to be achieved in order that this is done
      effectively.

PMID- 11966833
TI  - Factors influencing the severity of radiation skin and oral mucosal reactions:
      development of a conceptual framework.
AB  - Radiation skin and oral mucosa reactions are common side-effects of head and neck
      radiation therapy caused by damage to normal tissue. This damage can be dose
      limiting, meaning that the severity of acute reactions particularly in the oral
      mucosa may require time off treatment, potentially interfering with the
      effectiveness of radiation therapy in terms of tumour eradication. The purpose of
      this paper was to identify potential individual patient factors that may
      contribute to increasing severity of radiation skin and mucosal reactions.
      Sufficient literature and clinical observation is available to suggest that the
      variability in the degree of radiation reaction experienced by the patient is not
      due solely to the radiation received but that particular individual
      characteristics contribute to the expression of radiation damage in normal
      tissue. The identified factors fall into three broad categories: radiation
      therapy, genetic and personal factors. The research conducted on the predictive
      value of these factors is discussed. The inclusion of influencing factors in the
      assessment of people at risk for radiation skin and oral mucosa reactions has
      particular relevance for individualizing the prevention and management of
      radiation reactions.

PMID- 11966834
TI  - The use of complementary therapies among breast and prostate cancer patients in
      Finland.
AB  - This study describes the use of complementary therapies (CTs) among breast
      (women) and prostate cancer patients (men) in Finland. The data were collected
      using a self-administered postal questionnaire. Responses were received from 216
      women (response rate 54.9%) and 190 men (response rate 55.4%). Data analysis was
      based on descriptive statistics, the chi-square test and Fisher and Wilcoxon
      tests. Interpretation of the responses to the open-ended questions used the
      method of content analysis. Half the respondents (women 53%, men 50%) were
      interested in CTs. Women (59%) had seriously considered using CTs significantly
      (P = 0.006) more often than men (44%). Among the women and men who had considered
      the option, CT use was not started because there was not enough scientific
      evidence (women 56%, men 77%) or because conventional treatments had worked well
      enough (women 45%, men 70%). Almost one-third of all women (30%) and men (28%)
      either continued to use or started using CTs after they had fallen ill with
      cancer. They resorted to CTs in order to restore their hope in the future (women
      36%, men 36%) and to do as much as they could for themselves (women 46%, men
      29%). The results indicate that cancer patients are interested in CTs and use
      them quite frequently. This presents a major challenge to official health care:
      how should cancer patients be supported in the care relationship to make an
      informed decision about using CTs; what kind of advice should they be given; and
      how can patients' individual requirements be adequately met in nursing care?

PMID- 11966835
TI  - Patients' experiences of the recovery period 3 months after gastrointestinal
      cancer surgery.
AB  - It is known that patients who have undergone gastrointestinal surgery as a result
      of a tumour experience changes in weight and intake of food and fluid. Several
      studies have highlighted patients' experiences owing to cancer, but there is a
      lack of knowledge about the recovery period from the patients' perspective. The
      purpose of this research is to describe patients' experiences of the recovery
      period 3 months after surgery. Data was collected by inviting four women and six
      men, between 52 and 84 years of age, to participate in an interview or dialogue 3
      months after surgery. The study takes a hermeneutic approach. The framework for
      interpretation is the theory "Man's search for meaning" and further theories
      about suffering. The recovery period is characterized by feelings of being "down
      in the depths", lonely, abandoned and disappointed, but also feelings of support.
      Some patients regained strength and energy and reached a turning point, while
      others did not. Patients' suffering is seen as being in limbo, a fight between
      lack of freedom and freedom, including feelings of hope and doubts.

PMID- 11966836
TI  - Thenar metastasis from lung cancer.
AB  - We report an unusual occurrence of skin metastasis to the thenar eminence. Skin
      metastasis reflects the progression of the primary malignancy. Biopsy should be
      performed from the skin lesions, even those located at uncommon sites, for
      patients who have a history of uncontrolled lung cancer.

PMID- 11966837
TI  - Forum for Applied Cancer Education and Training (FACET).

PMID- 11966844
TI  - Manufacturing challenges in the commercial production of recombinant coagulation
      factor VIII.
AB  - Advances in gene technology have led to the development of a method to
      manufacture recombinant coagulation Factor VIII (rFVIII) for haemophilia A.
      Because rFVIII is a large and complex protein, its commercialization has required
      that many challenges in manufacturing, purification and processing be overcome.
      In order to license the first generation of rFVIII (Kogenate) in 1993, Bayer
      Corporation invested over 10 years in research and manufacturing development.
      Seven additional years were subsequently devoted to research and manufacturing
      improvements in order to accomplish the recent licensing of a second rFVIII
      product (KOGENATE Bayer or Kogenate FS). This product differs from its
      predecessor, in that human albumin is removed from the purification and the
      formulation steps. In addition, fewer chromatography steps are involved resulting
      in greater yields per mL of conditioned medium, and a solvent-detergent viral
      inactivation step replaces the heat-processing step used for the previous
      product. Despite these changes in the manufacturing, the protein backbone and
      carbohydrate structure of the final rFVIII molecule are identical. The complexity
      of the production processes is reflected by over 100 000 manufacturing data
      entries and by 600 quality control tests for each batch of rFVIII. Manufacturers
      are continuing to develop the next generation of rFVIII, which will be produced
      without the addition of any human or animal proteins or byproducts. Investments
      in research, development and manufacturing technology are expected to result in
      the development of new products with enhanced safety profiles, and in an increase
      in the production capacity for products that are chronically in short supply.

PMID- 11966845
TI  - Pathogen safety of manufacturing processes for biological products: special
      emphasis on KOGENATE Bayer.
AB  - Manufacturers of human therapeutic proteins derived from biological sources
      continuously strive to improve the pathogen safety profiles of these products.
      Efforts to improve pathogen safety margins for these biological products are
      directed towards several areas within the manufacturing processes including: (a)
      sourcing and screening of raw materials (b) determining the potential for
      manufacturing processes to reduce pathogen titres, and (c) incorporating methods
      designed specifically to remove or inactivate contaminating pathogens. Methods
      that could potentially reduce pathogen titres are a major focus for many
      manufacturers. In general, these methods are grouped into two categories,
      pathogen clearance and pathogen inactivation. Assessments are performed on small
      scale, laboratory simulations of the manufacturing process of interest that are
      spiked with a known amount of a selected pathogen. These studies provide
      estimates of the potential for a process step to remove or inactivate a
      particular pathogen. There are several pathogen clearance/inactivation methods
      that are inherent in manufacturing processes, however, some methods are
      intentionally incorporated into manufacturing for the sole purpose of reducing
      putative pathogen titres. Not only are well-known pathogens such as viruses
      targeted, but also suspected pathogens such as those associated with the
      transmissible spongiform encephalopathies (TSEs). The production processes for
      the isolation of several biological products, including recombinant KOGENATE
      Bayer (Kogenate FS), have been evaluated for the ability to reduce pathogen
      titres and/or have been designed to incorporate methods for reducing potential
      pathogen safety risks. Several processing steps with the potential to reduce
      pathogen titres have been identified.

PMID- 11966846
TI  - European data of a clinical trial with a sucrose formulated recombinant factor
      VIII in previously treated haemophilia A patients.
AB  - To increase the safety of antihaemophilic treatment, the production process of
      full-length recombinant factor VIII (FVIII) KOGENATE Bayer (Kogenate FS) has been
      modified. Human albumin is no longer added as stabilizer during purification and
      in final formulation. Instead, the new KOGENATE Bayer production process uses
      sucrose as a stabilizer in the formulation and adds solvent/detergent virus
      inactivation step. An European clinical trial was carried out in Germany and
      France in previously treated patients with severe haemophilia A who had more than
      100 exposure days to exogenous FVIII. Pharmacokinetic data was analysed according
      to one-stage and chromogenic assays. Efficacy and safety during home therapy and
      in surgical procedures were evaluated; inhibitor formation was carefully
      monitored. Safety and efficacy were evaluated in 33 European patients for 24
      months. Patients received more than 13 million IU KOGENATE Bayer. Over 75% of
      patients accrued more than 100 exposure days with the new product. Of 875
      bleeding episodes, 90.7% were treated with 1 or 2 infusions and 75.8% of
      responses to treatment were rated as 'excellent' or 'good'. Prophylactic
      treatment was the most common mode of therapy (60.7% of infusions). The product
      was well-tolerated and FVIII recovery studies were consistent throughout the
      study period. Only 0.26% of adverse events were reported to be drug related. No
      evidence of de novo inhibitor formation was observed. Overall, KOGENATE Bayer was
      efficacious, safe and well-tolerated for the treatment of haemophilia A in
      multitransfused patients.

PMID- 11966847
TI  - Experience with KOGENATE Bayer in surgical procedures.
AB  - The study objectives were to assess the efficacy of KOGENATE Bayer (Kogenate FS)
      in achieving haemostasis during surgical procedures in patients with severe
      haemophilia A and to evaluate its safety when given in the doses needed for this
      purpose. Dosing for surgical procedures was in accordance with clinical practice
      in the management of haemophilia A patients during and after surgery. Efficacy
      was evaluated by estimated blood loss and assessment of haemostasis as determined
      by the attending physician. Safety was assessed by the incidence of adverse
      events related to study drug and the incidence of viral seroconversions. In
      total, 15 previously treated patients (PTPs) and seven previously untreated
      patients (PUPs)/minimally treated patients (MTPs) underwent 30 surgical
      procedures ranging from minor (port placement/tooth extraction) to major
      (orthopaedic endoprosthesis/brain tumour excision) surgery. The efficacy profile
      was good to excellent as assessed by the attending physician, and recorded blood
      loss was minimal to none. No adverse events were recorded that were related to
      study drug. No viral seroconversions were observed. In conclusion, KOGENATE Bayer
      was shown to be safe and efficacious in patients with severe haemophilia A during
      surgical procedures.

PMID- 11966848
TI  - Safety and efficacy of KOGENATE Bayer in previously untreated patients (PUPs) and
      minimally treated patients (MTPs).
AB  - Safety and efficacy of KOGENATE Bayer (Kogenate FS), a second-generation full
      length recombinant factor VIII formulated with sucrose as stabilizer and produced
      without the addition of human albumin during purification and the final
      formulation, was assessed in a prospective, international clinical trial
      including 31 previously untreated patients (PUPs) and minimally treated patients
      (MTPs) with severe haemophilia A in home therapy and surgery. Factor VIII
      inhibitor development was monitored and mutation type profiles were analysed. As
      of 30 June 2000, the patients received a total of 2.729 infusions (mean 88; range
      6-274) for bleeding episodes, surgery or prophylactic treatment. No unexpected
      drug-related adverse events were observed. Four patients developed an inhibitor
      after 3-12 exposure days (EDs). One patient successfully underwent immune
      tolerance treatment; inhibitors in two patients disappeared spontaneously with on
      demand treatment, while the inhibitor titre remains low in one patient. Twenty
      nine patients (93%) with more than 20 EDs can be regarded as at low risk for
      inhibitor development. In conclusion, KOGENATE Bayer is efficacious and well
      tolerated for treatment of children with severe haemophilia A. The incidence of
      inhibitor formation is not different to that observed with other recombinant or
      plasma-derived products.

PMID- 11966849
TI  - Inhibitor development in correlation to factor VIII genotypes.
AB  - Alloantibodies (inhibitors) against factor VIII (FVIII) develop in 20-30% of
      patients with severe haemophilia A and render classical FVIII substitution
      therapy ineffective. Several studies have shown that genetic factors, the type of
      FVIII gene mutation and immune response genes (e.g. the Major Histocompatibility
      Complexes), influence the risk of inhibitor formation. In particular, the type of
      FVIII gene mutation has proven to be a decisive risk factor. Patients with severe
      molecular gene defects (e.g. large deletions, nonsense mutations, intron-22
      inversion) and no endogenous FVIII synthesis have a 7-10 times higher inhibitor
      prevalence than patients with milder molecular gene defects (e.g. missense
      mutations, small deletions, splice site mutations). To date, at least 10 distinct
      classes of mutations have been shown which have differing risks of associated
      inhibitor formation. A challenging observation in inhibitor patients is the
      heterogeneity of the antibody epitopes with respect to their number and their
      specificity. At least five epitopes in the FVIII molecule have been identified
      that constitute the targets for antibodies in most inhibitor patients. These
      epitopes are located in the ar3 region and the A2, A3, C1, C2 domains which
      correspond to the functional binding sites of the ligands of the FVIII protein.
      At present, the determinants of the characteristics of these epitopes and the
      subsequent inhibitor titre are unknown. A relationship of the mutation site and
      the epitope localization has been shown for some individual patients with mild
      haemophilia A. However, in severely affected haemophilia A patients, the
      influence of patient genetics on inhibitor titre and epitope specificity has yet
      to be elucidated.

PMID- 11966850
TI  - Comparative pharmacokinetic studies in haemophilia.
AB  - The general rules of pharmacokinetics have been applied to the study of the
      behaviour of clotting factor concentrates in patients with haemophilia. Since
      1980, the continuous development of innovative plasma- and rDNA-derived
      concentrates and the implementation of new virucidal methods in manufacturing
      processes has prompted us to define a standard approach to this issue. Model
      based methods, based upon one or two open compartment models, were available when
      this work was initiated. Unfortunately, these methods are supported by very
      little biological data and are profoundly affected by the goodness-of-fit of the
      data. In contrast, the model-independent method, which is not affected by errors
      in fitting, provides reproducible and reliable estimates of the behaviour of
      clotting factor concentrates in patients with haemophilia. Further, the
      calculations required for the model-independent method are quite simple and can
      be computed using a pocket minicomputer. The need for an accurate standardization
      has been recognized by the Factor VIII/IX Sub-Committee which, in 1991, issued
      the first recommendations on the pharmacokinetic evaluation of Factor VIII/IX
      concentrates. A recent revision of the recommendations has been made available on
      the web site of the International Society on Thrombosis and Haemostasis. The most
      crucial changes - sample size, study design, dosages in single-dose studies,
      potency assessment, need for well-defined standards, optimal number of points,
      and most important outcomes - are discussed in this report. In addition, the
      model-independent and compartmental methods are described.

PMID- 11966851
TI  - Aspects of haemophilia prophylaxis in Sweden.
AB  - Prophylactic treatment of haemophilia has been gaining acceptance as the optimal
      therapeutic option in an increasing number of haemophilia centres in the
      developed world in recent years. This paper focus on three aspects of
      prophylactic therapy: when to start treatment, venous access and the dose/dose
      interval. Evidence is in favour of prophylactic treatment to be started at an
      early age using either a peripheral vein with 1-2 injections per week and a
      successive increase in the frequency depending on the child and the veins, or,
      using a Port-A-Cath which allows a better prophylactic coverage by infusions
      preferably every second day in haemophilia A and every third day in haemophilia
      B.

PMID- 11966852
TI  - Results of an orthopaedic survey in young patients with severe haemophilia in
      Spain.
AB  - This paper outlines the results obtained in a cross-sectional study of a group of
      young patients with severe haemophilia A and B. The primary aim of the study was
      to ascertain the level of orthopaedic complications in the group, the effects
      that these complications have on quality of life, and the medical resources used
      on these patients. The secondary aim was to relate their current orthopaedic
      state to the type of treatment received before the study. The study was carried
      out in 11 hospitals in Spain, where 70 severe haemophilia patients (factor VIII
      [FVIII] < 2%), with an average age of 21.6 and a median age of 22, and no
      inhibitors, were monitored. The percentage of patients suffering from articular
      complaints was 84.3% and 85.7% according to the Gilbert and Petterson scales,
      respectively. Furthermore, pain was reported in 16.1% of joints, most frequently
      in ankles. Using the SF-36 Health Survey, patients were observed to have a poorer
      quality of life relative to healthy controls. Despite high levels of both the
      coagulant factor given to patients and the financial resources dedicated to their
      treatment, the type of treatment (on demand and/or as secondary prophylaxis)
      provided to the young adults was found to be incapable of preventing haemophilic
      arthropathy and subsequent negative quality of life consequences.

PMID- 11966853
TI  - Effects of prophylactic treatment regimens in children with severe haemophilia: a
      comparison of different strategies.
AB  - Both Sweden and the Netherlands have a long experience with primary prophylaxis
      in children with severe haemophilia. In these countries it has been offered to
      all children for the last 3-4 decades. In Sweden prophylaxis is generally started
      at an earlier age with a higher dosage and frequency than in the Netherlands.
      Patients in the Netherlands receive a more individually tailored regimen, with
      prophylaxis now started after the first one or two joint bleeds and dosages are
      increased when breakthrough bleeds occur. The current study evaluated the effect
      prophylaxis on long-term outcomes and the consumption of clotting factor
      concentrates in Dutch and Swedish cohorts. Our results show that the orthopaedic
      outcome in the oldest groups of patients from Sweden and the Dutch cohorts were
      comparable, although the Swedish patients used twice as much clotting products
      per year. In the youngest patients, joint status is very good and further follow
      up is necessary to demonstrate the benefits of either strategy. In conclusion,
      more individually tailored regimens aimed at preventing bleeding prevent joint
      damage in children with severe haemophilia, while clotting factor consumption is
      about half of that in previously described regimens.

PMID- 11966854
TI  - Pilot testing of the 'Haemo-QoL' quality of life questionnaire for haemophiliac
      children in six European countries.
AB  - In a multinational working group, an instrument (Haemo-QoL) to assess quality of
      life in children/adolescents with haemophilia and their parents has been
      developed. In co-operation with haemophilia treatment centres in six European
      countries, approximately 10 children/adolescents with haemophilia per country and
      their parents were asked to participate in the pilot-testing. Both self-reported
      and parent-reported questionnaires were provided for two age-groups of children
      (4-16 years). Medical data was collected from physicians from patient files.
      Answers to open questions from participants (58 children and 57 parents)
      confirmed the content of 116 of the preliminary items. Cognitive debriefing
      revealed that the majority of the Haemo-QoL was rated favourably, but 29
      questions were recommended to be omitted and several items to be reformulated.
      Preliminary psychometric testing of the revised 77 item questionnaire in the same
      sample showed acceptable reliability and validity, which will be examined in a
      subsequent study with a larger patient sample.

PMID- 11966855
TI  - The concept of idiotypic vaccination against factor VIII inhibitors in
      haemophilia A.
AB  - Idiotypic vaccination has proven successful in several animal models and human
      trials. Here we suggest that the expression of cross-reactive idiotypes on factor
      VIII (FVIII) inhibitors of patients with haemophilia A, patients with anti-FVIII
      autoimmune disease and natural anti-FVIII antibodies of healthy individuals,
      together with the ability of anti-idiotypic reagents to neutralize anti-FVIII
      antibodies, provides a rationale for designing a vaccine strategy aimed at
      preventing the occurrence of or suppressing inhibitors, based on the induction of
      protective anti-idiotypes. Here we discuss the rationale supporting the concept
      of using idiotypic vaccination to prevent the occurrence of FVIII inhibitors in
      patients with haemophilia A.

PMID- 11966856
TI  - Parvovirus-mediated gene transfer for the haemophilias.
AB  - Gene therapy may revolutionize the treatment of haemophilia. Effective gene
      therapy requires sustained therapeutic levels of factors IX (FIX) and VIII. Adeno
      associated virus (AAV) is a member of the parvovirus family, is a nonpathogenic
      virus with a broad host cell range, and does not provoke a significant immune
      response upon infection. These favourable characteristics make AAV a suitable
      gene transfer vector for factor deficient patients. A new understanding of AAV
      biology coupled with novel AAV vector designs suggest that the goal of effective
      gene transfer is within reach. We review here recent advances in AAV vectors used
      for gene transfer of the haemophilias.

PMID- 11966857
TI  - Migraine management: contrasting patient preferences with current clinical end
      points: introduction.

PMID- 11966858
TI  - What do patients with migraine want from acute migraine treatment?
AB  - Migraine is a common chronic condition with an ever-expanding therapeutic
      armamentarium. As therapeutic options multiply, it is increasingly important to
      understand patients' attitudes and preferences regarding various treatment
      characteristics. Several strategies have evolved to establish treatment
      priorities in migraine and rationalize and prioritize end points and outcomes to
      meet the needs of patients. A survey of a population-based sample of migraineurs
      indicated that an overwhelming majority of patients consider complete relief of
      head pain, no recurrence, and rapid onset of action as important or very
      important attributes of acute migraine therapy. An analysis of the relationship
      between clinical end points and satisfaction found that more than 90% of patients
      who were pain-free at 2 hours were at least somewhat satisfied with treatment,
      but satisfaction was dependent on relatively rapid relief. Using a "willingness
      to-pay" approach, results indicated that while patients will pay more for
      migraine treatment that produces rapid, consistent relief without adverse effects
      or recurrence, speed of complete relief is the most valued attribute. By
      assessing physician preferences and practices, degree of pain relief and rapid
      onset were identified as the most important attributes of acute therapy. Based on
      results from preference studies of triptans, 50% of patients cited more rapid
      pain relief as the most important determinant of treatment preference. Based on
      these various approaches, the consensus view is that both clinicians and patients
      desire a broad range of positive migraine treatment attributes, but rapid onset
      of complete pain relief is a particularly important priority.

PMID- 11966859
TI  - Clinical benefits of early triptan therapy for migraine.
AB  - Although triptans have been proven effective for acute treatment of migraine,
      reserving them for moderate or severe pain may produce suboptimal pain relief and
      higher rates of recurrence. Recent evidence indicates that early intervention at
      the onset of pain improves outcomes. Post hoc analysis of a long-term, open-label
      European study of almotriptan 12.5 mg found that the percentage of attacks
      rendered pain-free at 2 hours was significantly greater when patients treated
      mild pain (84%) than when the intervention occurred during moderate or severe
      pain (53%). A similar pattern emerged with respect to the consistency of pain
      relief, with a significant advantage for early intervention (88% versus 56%,
      respectively). A difference in favor of early intervention was also seen with
      respect to recurrence, need for rescue medication, and adverse events. The
      recurrence rate was significantly lower in patients treating mild pain (28%) than
      in those delaying treatment until the pain became moderate or severe (33%), which
      suggests that achieving pain freedom results in less recurrence. These results
      were generally replicated in post hoc analysis of a subgroup of patients from a
      randomized, placebo-controlled trial (the Spectrum Study) of oral sumatriptan 50
      mg in migraineurs. This analysis demonstrated that with early intervention, pain
      was less likely to intensify, fewer attacks required redosing, more attacks
      remained pain-free 24 hours postdose, and normal function returned more quickly.
      In sum, early intervention with triptans can improve outcomes, avoiding much of
      the pain and disability associated with treating moderate or severe attacks.

PMID- 11966860
TI  - Tripstar: a comprehensive patient-based approach to compare triptans.
AB  - Several second-generation triptans have been introduced that differ in their
      pharmacologic profiles relative to each other and to sumatriptan. As therapeutic
      options multiply, clinicians must be able to distinguish among these compounds.
      Recently, a meta-analysis was conducted on data from 53 double-blind, randomized,
      placebo- or active-controlled trials involving over 24,000 patients receiving
      oral triptans. Results indicated that almotriptan 12.5 mg, rizatriptan 10 mg, and
      eletriptan 80 mg are generally superior to sumatriptan 100 mg based on individual
      treatment attributes, such as pain relief, sustained pain freedom, consistency of
      response, and tolerability. Meta-analyses are limited, however, as the analysis
      can only be performed for individual end points, whereas patients and prescribers
      balance a variety of treatment attributes when assessing drug acceptability. A
      flexible overall scoring system ("Tripstar") is proposed that compares triptans
      to a hypothetical "ideal" using meta-analysis data combined with ratings of the
      relative importance of clinically relevant treatment criteria. An informal test
      of the Tripstar model indicated that sumatriptan is most similar to a
      hypothetical ideal for both mild and severe migraine, primarily due to its high
      worldwide clinical exposure. However, after exclusion of worldwide exposure as a
      contributing factor, almotriptan 12.5 mg is most similar to the ideal,
      principally because of its good tolerability. Further tests of the Tripstar model
      are planned that will gauge the relative importance of a broader range of
      attributes.

PMID- 11966861
TI  - Almotriptan reduces the incidence of migraine-associated symptoms: a pooled
      analysis.
AB  - OBJECTIVES: Evaluate the reduction in migraine-associated symptoms after
      administration of a single oral dose of almotriptan. METHODS: This pooled
      analysis (N=1773) used data from three randomized, placebo-controlled, phase III
      trials (studies A, B, and C) to determine the incidence of migraine-associated
      symptoms (defined as nausea, vomiting, photophobia, and phonophobia) 2 hours
      after a single oral dose of study medication (almotriptan, sumatriptan, or
      placebo). Outcome data was extracted from studies A and B for placebo and the
      almotriptan 6.25-mg and 12.5-mg groups, and from study C for placebo, almotriptan
      12.5-mg, and sumatriptan 100-mg groups. RESULTS: The incidence of nausea,
      photophobia, and phonophobia at 2 hours after dosing with study medication was
      significantly reduced (all P <.05) with almotriptan 6.25 mg or 12.5 mg compared
      with placebo. The percentage of patients with vomiting was lower with both doses
      of almotriptan in studies A and B compared with placebo, although differences
      were significant only for the 6.25-mg dose in study A (P <.001). For study C, the
      incidence of nausea, vomiting, photophobia, and phonophobia was similar for
      almotriptan and sumatriptan and lower than with placebo at 2 hours after dosing.
      Significant reductions (all P <.05) versus placebo were observed in the incidence
      of vomiting and phonophobia with almotriptan 12.5 mg, and photophobia and
      phonophobia with sumatriptan 100 mg. CONCLUSION: Almotriptan provides relief from
      migraine-associated symptoms of nausea, vomiting, photophobia, and phonophobia,
      and thus represents an attractive treatment option for a wide spectrum of
      migraine symptomatology.

PMID- 11966862
TI  - Almotriptan increases pain-free status in patients with acute migraine treated in
      placebo-controlled clinical trials.
AB  - OBJECTIVES: Evaluate the efficacy of a single oral dose of almotriptan in
      achieving pain-free status during treatment of acute migraine attacks. METHODS:
      This pooled analysis (N=1321) used data from two randomized, placebo-controlled,
      phase III trials (studies A and B) to determine the proportion of patients with
      migraine achieving pain-free status 2 hours after a single oral dose of study
      medication (almotriptan or placebo). Pain was assessed using a 4-point integer
      scale (0=no headache, 3=severe headache), and recorded in a patient self
      assessment booklet. RESULTS: The proportion of patients pain-free at 2 hours
      after study medication was significantly greater with almotriptan 6.25 mg (both
      studies P<or=.002) and almotriptan 12.5 mg (both studies P<or=.001) than with
      placebo. In study A, 11.6% of patients taking almotriptan 12.5 mg versus 2.5% of
      patients receiving placebo were pain-free at 1 hour (P=.016). At 1.5 hours, 26.8%
      of patients taking almotriptan 12.5 mg versus 8.8% receiving placebo (P=.001)
      were pain-free, and at 2 hours, 38.4% on almotriptan versus 11.3% on placebo were
      pain-free (P<.001). In study B, 23.8% of patients taking almotriptan 12.5 mg were
      free from pain at 1.5 hours versus 10.2% receiving placebo (P<.001). At 2 hours,
      39.2% taking almotriptan 12.5 mg versus 15.3% receiving placebo were pain-free
      (P<.001). Increases in pain-free status with almotriptan generally occurred in a
      dose-dependent manner. CONCLUSION: Compared with placebo, almotriptan 12.5 mg
      significantly increases the proportion of patients who are pain-free by as early
      as 1 hour, and consistently by 1.5 hours, after a single dose.

PMID- 11966863
TI  - Impact of chest pain on cost of migraine treatment with almotriptan and
      sumatriptan.
AB  - Chest-related symptoms occur with all triptans; up to 41% of patients with
      migraine who receive sumatriptan experience chest symptoms, and 10% of patients
      discontinue treatment. Thus, the cost of chest pain-related care was estimated in
      migraineurs receiving almotriptan 12.5 mg versus sumatriptan 50 mg. A population
      based, retrospective cohort study used data to quantify the incidence and costs
      of chest pain-related diagnoses and procedures. An economic model was constructed
      to estimate annual cost savings per 1000 patients receiving almotriptan versus
      sumatriptan based on the reported rates of chest pain. Annual direct medical cost
      avoided was calculated for a hypothetical health plan covering 1 million lives.
      Among a cohort of 1390 patients, the incidence of chest pain-related diagnoses
      increased significantly by 43.6% with sumatriptan (P=.003). Aggregate costs for
      chest pain-related diagnoses and procedures increased from $22,713 to $30,234.
      Payments for inpatient hospital services, costs for primary care visits, and
      costs for outpatient hospital visits increased by over 100%, 53.1%, and 14.4%,
      respectively. The model predicted $11,215 in direct medical cost savings annually
      per 1000 patients treated with almotriptan versus sumatriptan. Annual direct
      medical costs avoided totaled $194,358, and when applied to recent estimates of
      86 million lives currently covered by almotriptan treatment, translates into an
      annual cost savings of just under $17 million for chest pain and associated care.
      Thus, using almotriptan in place of sumatriptan will likely reduce the cost of
      chest pain-related care.

PMID- 11966864
TI  - Helicobacter pylori-related iron deficiency anemia: a review.
AB  - Several clinical reports have demonstrated that Helicobacter pylori gastric
      infection has emerged as a new cause of refractory iron deficiency anemia,
      unresponsive to iron therapy, and not attributable to usual causes such as
      intestinal losses or poor intake, malabsorption or diversion of iron in the
      reticulo-endothelial system. Although the interaction between infection and iron
      metabolism is now well consolidated, our understanding of the pathogenetic
      mechanism underlying the anemia is still wanting. Microbiological and
      ferrokinetic studies seem to suggest that Helicobacter pylori infected antrum
      could act as a sequestering focus for serum iron by means of outer membrane
      receptors of the bacterium, that in vitro are able to capture and utilize for
      growth iron from human lactoferrin. The proposed hypothesis does not answer why
      this complication is such a rare disease outcome in a common human infection but
      it may be used as a template for further controlled studies to determine the
      mechanisms of this atypical, medically important putative sequelae of H. pylori
      infection.

PMID- 11966865
TI  - Age at acquisition of Helicobacter pylori in a pediatric Canadian First Nations
      population.
AB  - BACKGROUND: Few data exist regarding the epidemiology of Helicobacter pylori
      infections in aboriginal, including the First Nations (Indian) or Inuit (Eskimo)
      populations of North America. We have previously found 95% of the adults in
      Wasagamack, a First Nations community in Northeastern Manitoba, Canada, are
      seropositive for H. pylori. We aimed to determine the age at acquisition of H.
      pylori among the children of this community, and if any association existed with
      stool occult blood or demographic factors. MATERIALS AND METHODS: We
      prospectively enrolled children resident in the Wasagamack First Nation in August
      1999. A demographic questionnaire was administered. Stool was collected, frozen
      and batch analyzed by enzyme-linked immunosorbent assay (ELISA) for H. pylori
      antigen and for the presence of occult blood. Questionnaire data were analyzed
      and correlated with the presence or absence of H. pylori. RESULTS: 163 (47%) of
      the estimated 350 children aged 6 weeks to 12 years, resident in the community
      were enrolled. Stool was positive for H. pylori in 92 (56%). By the second year
      of life 67% were positive for H. pylori. The youngest to test positive was 6
      weeks old. There was no correlation of a positive H. pylori status with gender,
      presence of pets, serum Hgb, or stool occult blood. Forty-three percent of H.
      pylori positive and 24% of H. pylori negative children were < 50th percentile for
      height (p = 0.024). Positive H. pylori status was associated with the use of
      indoor pail toileting (86/143) compared with outhouse toileting (6/20) (p =
      0.01). CONCLUSIONS: In a community with widespread H. pylori infection,
      overcrowded housing and primitive toileting, H. pylori is acquired as early as 6
      weeks of age, and by the second year of life 67% of children test positive for H.
      pylori.

PMID- 11966866
TI  - Cardiovascular risk factors in subjects with Helicobacter pylori infection.
AB  - BACKGROUND: It has been proposed that Helicobacter pylori infection is related to
      cardiovascular disease, although this has not been fully investigated. The aim of
      this study was to investigate whether H. pylori infection is associated with
      cardiovascular risk factors. SUBJECTS AND METHODS: One thousand six hundred and
      fifty people undergoing annual medical checks at Shimane Institute of Health
      Science between September 1998 and August 1999 were enrolled. Gender, age, body
      mass index, habitual smoking and drinking, systolic and diastolic blood pressure,
      serum level of total cholesterol, triglyceride, high-density lipoprotein
      cholesterol (HDLC), blood glucose, leukocyte count and hemoglobin were compared
      between H. pylori seropositive and seronegative cases. RESULTS: In H. pylori
      seropositive individuals, HDLC was significantly lower than that in seronegative
      individuals. After adjustment for possible confounding factors (gender, age, BMI,
      smoking and drinking habits), mean HDLC in H. pylori-seropositive and
      seronegative individuals were 56.1 and 58.2 mg/dl, respectively (p <.005). The
      percentage of the elderly (over 50 years old) individuals with HDLC < 35 mg/dl in
      H. pylori seropositive and seronegative groups were 7.4% and 4.7%, respectively
      (p <.001). In addition, the lower HDLC level was accompanied by an increased
      leukocyte count. CONCLUSION: Long-term infection with H. pylori may have an
      important role in decreasing the serum HDLC concentration.

PMID- 11966867
TI  - Helicobacter pylori eradication in patients on long-term H2 receptor antagonists.
      Economic and symptomatic benefits. A large prospective study in primary care.
AB  - BACKGROUND: A large proportion of patients in primary care are still being
      maintained on long-term acid suppression, without any attempts to identify
      Helicobacter pylori status and to treat those that test positive. OBJECTIVES: To
      assess the prevalence and economic and symptomatic benefits of H. pylori
      eradication in patients maintained on long-term H2 receptor antagonists (H2RA) in
      primary care. PATIENTS AND METHODS: Patients on long-term (i.e. 6 months or
      longer) H2RA were identified from the computerised records of six practices in
      north England. Helicobacter pylori status was identified using serology and H.
      pylori positive patients were then offered standard 7-day proton pump based
      triple therapy, followed by a urea breath test (UBT) to confirm H. pylori
      eradication. Those who had a positive UBT were offered a second line course of H.
      pylori eradication therapy. Follow up period was 1 year. The main outcome
      measures were improvement in dyspepsia symptom scores, amount of H2RA being
      consumed, and economic benefits after H. pylori eradication. RESULTS: One
      thousand and seven patients (1.5%) were identified on long-term H2RA, of whom 471
      (46%) ultimately had their H. pylori serology assessed. Sixty-three (297) percent
      of the patients tested had a positive serology for H. pylori, the majority of
      whom (58%, 172) had prior evidence of peptic ulcer disease. The mean duration of
      therapy and mean time since endoscopy/barium studies was significantly longer in
      patients with peptic ulcer disease compared to their counterparts with nonulcer
      dyspepsia and gastro-oesophageal reflux disease, p =.0002 and.0001, respectively.
      After successful H. pylori eradication (which was possible in 84% of the
      patients), at the end of the 1-year study period, on an intention to treat basis
      62% of the patients could either stop or significantly reduce dosage of their
      H2RA. There was also significant reduction in the mean dose of H2RA being
      consumed and severity of symptoms at the end of the study period (p <.00001).
      CONCLUSION: Almost two-thirds of patients on long-term H2RA in primary care will
      have a positive serology for H. pylori; the majority of these will have peptic
      ulcer disease. In over 60% of cases H. pylori eradication led to significant
      improvement in symptom scores and reduction in dosage of H2RA being consumed.
      Cessation or reduction in long-term H2RA prescribing is cost effective.

PMID- 11966868
TI  - Amoxicillin/tetracycline combinations are inadequate as alternative therapies for
      Helicobacter pylori infection.
AB  - BACKGROUND: Triple therapy with proton pump inhibitors or ranitidine bismuth
      citrate, clarithromycin and either amoxicillin or nitroimidazole derivatives are
      the present gold standards for cure of Helicobacter pylori infection. However,
      primary resistance to either clarithromycin or nitroimidazole derivatives is
      increasing and alternative therapies are needed. AIM: To determine the efficacy
      and safety of three regimens consisting of amoxicillin and tetracycline or
      doxycycline combined with either lansoprazole or ranitidine bismuth citrate.
      METHODS: Two hundred and seventy H. pylori infected patients were randomly given
      one of the following treatments: amoxicillin 1 g twice a day (b.i.d.) plus
      tetracycline 500 mg four times a day (q.i.d.) with either lansoprazole 30 mg
      b.i.d. (group LAT) or ranitidine bismuth citrate 400 mg b.i.d. (group RBCAT) for
      7 days and amoxicillin 1 g b.i.d. plus doxycycline 100 mg b.i.d. and lansoprazole
      30 mg b.i.d. for 14 days (group LAD). Eradication rate was assessed by UBT at 4-6
      weeks after therapy. RESULTS: The three groups (LAT, RBCAT, and LAD) of patients
      achieved eradication rates of 35% (25-45), 20% (12-29) and 36% (25-46),
      respectively, on intention-to-treat analysis. Patient compliance was optimal and
      side-effects minimal in all three groups. CONCLUSIONS: Although the
      amoxicillin/tetracycline combination is attractive (inexpensive, safe, and with
      low primary resistance rate), it can not be recommended for H. pylori
      eradication.

PMID- 11966869
TI  - The use of an oral fluid immunoglobulin G ELISA for the detection of Helicobacter
      pylori infection in children.
AB  - BACKGROUND: Enzyme linked immunosorbent assay (ELISA) evaluation of oral fluid
      immunoglobulin G (IgG) antibodies to Helicobacter pylori is a unique approach for
      both epidemiological studies and the diagnosis of infection, especially in
      children. The use of oral fluid sampling to evaluate specific H. pylori IgG
      antibodies has advantages over serum, including reduced biohazard risk and
      noninvasive collection. Oral fluid sampling is fast and involves minimal patient
      discomfort. Since children facilitate transmission of H. pylori infection, a
      simple, accurate, noninvasive diagnostic test is necessary for large
      epidemiologic studies. The aim of our study was to evaluate a new oral fluid
      ELISA for detection of IgG antibodies to H. pylori in children. MATERIALS AND
      METHODS: We compared this new oral fluid ELISA with the HM-CAPTM serum ELISA and
      gastric biopsy histology using 779 oral fluid samples from children collected at
      11 clinical sites across the United States. This cohort included 315 children
      symptomatic for abdominal pain and 464 asymptomatic. All samples were evaluated
      in a double blind manner. The oral fluid ELISA demonstrated a sensitivity of
      76.2% and a specificity of 94.0% in children 2 months old to 201/2 years, as
      compared with the HM-CAPTM serologic assay. The assay's sensitivity improved to
      81.3% in children aged 5 or greater and the specificity remained at 94.0%. When
      compared with gastric biopsy histology in the same age group, the oral fluid
      ELISA demonstrated a sensitivity of 71.7% and a specificity of 90.4%. RESULTS:
      This new oral fluid ELISA is moderately sensitive and offers a very specific
      method for detecting H. pylori infection in older children, but it is of little
      value in children under the age of 5 years. CONCLUSIONS: Overall, we conclude
      that this oral fluid ELISA does not appear to be a helpful clinical tool for the
      diagnosis of H. pylori infection in children.

PMID- 11966870
TI  - Peptic ulcer disease in children without Helicobacter pylori infection.

PMID- 11966871
TI  - Removal of mucus for ultrastructural observation of the surface of human gastric
      epithelium using pronase.
AB  - BACKGROUND: Helicobacter pylori adhering to the human gastric epithelium causes
      gastric diseases such as ulcer, carcinoma and lymphoma. It is thus important to
      observe in detail both the surface of the epithelial cells and the H. pylori that
      adhered to it for the elucidation of H. pylori-induced diseases by scanning
      electron microscopy (SEM). Since the thick mucus layer blocks the observation of
      the cell surface and the bacteria, it is generally eliminated during the
      processing for SEM by roughly mechanical methods, but these treatments also
      demolish the ultrastructure of the cells. We studied the nonmechanical method for
      removal of mucus layer of gastric epithelium using pronase. MATERIALS AND
      METHODS: To determine the optimal concentration of pronase, mucin was used as a
      substrate for inhibition of the viscosity. Pronase was added in 2% mucin at the
      concentration of 10, 50, 100, 500, 1000, 2000 or 5000 unit/ml and the flowing
      time of the mixture was measured. Based on the digestion experiment, biopsied
      specimens from 24 patients with dyspepsic symptoms were fixed in glutaraldehyde
      and then washed in rolling with different concentration of pronase. After the
      pretreatment by pronase, the specimens were treated according to the standard
      process for SEM. RESULTS: We succeeded in removing the mucus layer on the surface
      of epithelial cells from the biopsied specimens fixed in glutaraldehyde by
      rinsing with 2000 unit/ml pronase for 24 hours. CONCLUSIONS: Using our digestive
      method without destroying the ultrastructure, the earliest stage which H. pylori
      has adhered onto the human gastric epithelium can be observed for the
      investigation of H. pylori-induced gastric disorders by SEM.

PMID- 11966872
TI  - Up-regulation of inducible nitric oxide synthase and nitric oxide in Helicobacter
      pylori-infected human gastric epithelial cells: possible role of interferon-gamma
      in polarized nitric oxide secretion.
AB  - BACKGROUND: Nitric oxide (NO) generated by nitric oxide synthase (NOS) is known
      to be an important modulator of the mucosal inflammatory response. In this study,
      we questioned whether Helicobacter pylori infection could up-regulate the
      epithelial cell inducible NOS (iNOS) gene expression and whether NO production
      could show polarity that can be regulated by immune mediators. MATERIALS AND
      METHODS: Human gastric epithelial cell lines were infected with H. pylori, and
      the iNOS mRNA expression was assessed by quantitative RT-PCR. NO production was
      assayed by determining nitrite/nitrate levels in culture supernatants. To
      determine the polarity of NO secretion by the H. pylori-infected epithelial
      cells, Caco-2 cells were cultured as polarized monolayers in transwell chambers,
      and NO production was measured. RESULTS: iNOS mRNA levels were significantly up
      regulated in the cells infected with H. pylori, and expression of iNOS protein
      was confirmed by Western blot analysis. Increased NO production in the gastric
      epithelial cells was seen as early as 18 hours postinfection, and reached maximal
      levels by 24 hours postinfection. The specific MAP kinase inhibitors decreased H.
      pylori-induced iNOS and NO up-regulation. After H. pylori infection of polarized
      epithelial cells, NO was released predominantly into the apical compartment, and
      IL-8 was released predominantly into basolateral compartment. The addition of IFN
      gamma to H. pylori-infected polarized epithelial cells showed a synergistically
      higher apical and basolateral NO release. CONCLUSION: These results suggest that
      apical NO production mediated by MAP kinase in H. pylori-infected gastric
      epithelial cells may influence the bacteria and basolateral production of NO and
      IL-8 may play a role in the tissue inflammation.

PMID- 11966873
TI  - Effect of Helicobacter pylori-induced cyclooxygenase-2 on gastric epithelial cell
      kinetics: implication for gastric carcinogenesis.
AB  - BACKGROUND: Cyclooxygenase (COX)-2 induced by Helicobacter pylori is thought to
      enhance gastric carcinogenesis by affecting the maintenance of epithelial
      homeostasis. MATERIALS AND METHODS: Gastric biopsies from 160 subjects, 97 with
      nonulcer dyspepsia (47 H. pylori negative, 50 H. pylori positive) and 63 with
      gastric cancer were examined immunohistochemically for COX-2 expression, cell
      proliferation and apoptotic indices. RESULTS: COX-2 expression in corpus was
      significantly higher in H. pylori positive than in negative non-ulcer dyspepsia
      (NUD) (p <.05). Regardless of site, gastric cancer subjects had higher COX-2
      expression in both antrum and corpus compared with H. pylori negative and
      positive NUD (p <.005). Proliferation was higher in cancer and H. pylori positive
      than in negative NUD (p <.0001). Moreover, cancer had enhanced proliferation than
      H. pylori positive NUD in corpus greater (p =.0454) and antrum lesser (p =.0215)
      curvatures. Apoptosis was higher in H. pylori positive than in negative NUD (p
      <.05). However, both had a higher index than the cancer subjects (p <.0001).
      Apoptosis : proliferation ratio was higher in corpus of H. pylori negative than
      in positive NUD in greater (p =.0122) and lesser (p =.0009) curvatures. However,
      both had a higher A:P ratio than cancer cases (p =.0001). A negative correlation
      between COX-2 expression and A:P ratio was found in corpus greater (r = -.176, p
      =.0437) and lesser (r = -.188, p =.0312) curvatures. CONCLUSION: The expression
      of COX-2 is associated with disruption in gastric epithelial kinetics and hence
      may play a role in gastric carcinogenesis.

PMID- 11966874
TI  - The mouse colonizing Helicobacter pylori strain SS1 may lack a functional cag
      pathogenicity island.

PMID- 11966876
TI  - Molecular evolution of the cacophony IVS6 region in sandflies.
AB  - A number of insects produce acoustic signals during courtship. Genes involved in
      the control of the courtship song are particularly interesting from an
      evolutionary viewpoint because interspecific variation in this signal is
      potentially important as a reproductive isolation mechanism and, as a
      consequence, in the speciation process. The cacophony gene was identified by a
      mutation affecting the "lovesong" in Drosophila melanogaster. Phlebotomine
      sandflies (Diptera: Psychodidae) also produce acoustic stimuli during courtship
      and therefore cacophony can be used as an interesting molecular marker in
      evolutionary studies in these important disease vectors. In this paper we have
      studied the molecular evolution of the IVS6 region of cacophony in sandflies. We
      compared the level of divergence in the exon sequences encoding this conserved
      domain in Drosophila and Phlebotomines. We also analysed the high level of
      variation in an intron that is present in sandflies but that was lost in
      Drosophila during evolution. The available cacophony sequences were also used for
      a phylogenetic analysis of some species of the Neotropical genus Lutzomyia.

PMID- 11966878
TI  - Germ line transformation of the yellow fever mosquito, Aedes aegypti, mediated by
      transpositional insertion of a piggyBac vector.
AB  - Mosquito-vectored diseases such as yellow fever and dengue fever continue to have
      a substantial impact on human populations world-wide. Novel strategies for
      control of these mosquito vectored diseases can arise through the development of
      reliable systems for genetic manipulation of the insect vector. A piggyBac vector
      marked with the Drosophila melanogaster cinnabar (cn) gene was used to transform
      the white-eyed khw strain of Aedes aegypti. Microinjection of preblastoderm
      embryos resulted in four families of cinnabar transformed insects. An overall
      transformation frequency of 4%, with a range of 0% to as high as 13% for
      individual experiments, was achieved when using a heat-shock induced transposase
      providing helper plasmid. Southern hybridizations indicated multiple insertion
      events in three of four transgenic lines, while the presence of duplicated target
      TTAA sites at either ends of individual insertions confirmed characteristic
      piggyBac transposition events in these three transgenic lines. The transgenic
      phenotype has remained stable for more than twenty generations. The
      transformations effected using the piggyBac element establish the potential of
      this element as a germ-line transformation vector for Aedine mosquitoes.

PMID- 11966877
TI  - Isolation of cDNA clones encoding putative odourant binding proteins from the
      antennae of the malaria-transmitting mosquito, Anopheles gambiae.
AB  - One way of controlling disease transmission by blood-feeding mosquitoes is to
      reduce the frequency of insect-host interaction, thus reducing the probability of
      parasite transmission and re-infection. A better understanding of the olfactory
      processes responsible for allowing mosquitoes to identify human hosts is required
      in order to develop methods that will interfere with host seeking. We have
      therefore initiated a molecular approach to isolate and characterize the genes
      and their products that are involved in the olfactory recognition pathway of the
      mosquito Anopheles gambiae, which is the main malaria vector in sub-Saharan
      Africa. We report here the isolation and preliminary characterization of several
      cDNAs from male and female A. gambiae antennal libraries that encode putative
      odourant binding proteins. Their conceptual translation products show extensive
      sequence similarity to known insect odourant binding proteins (OBPs)/pheromone
      binding proteins (PBPs), especially to those of D. melanogaster. The A. gambiae
      OBPs described here are expressed in the antennae of both genders, and some of
      the A. gambiae OBP genes are well conserved in other disease-transmitting
      mosquito species, such as Aedes aegypti and Culex quinquefasciatus.

PMID- 11966879
TI  - Paraphyly in Hawaiian hybrid blowfly populations and the evolutionary history of
      anthropophilic species.
AB  - Complementary nuclear (28S rRNA) and mitochondrial (COI + II) gene markers were
      sequenced from the blowflies, Lucilia cuprina and Lucilia sericata, from Europe,
      Africa, North America, Australasia and Hawaii. Populations of the two species
      were phylogenetically distinct at both genes, with one exception. Hawaiian L.
      cuprina possessed typical L. cuprina-type rRNA, but had L. sericata-type
      mitochondrial (COI + II) sequences. An explanation for this pattern is that
      Hawaiian flies are hybrids and comparison of observed levels of sequence
      divergence to possible introduction events, e.g. Polynesian colonization,
      suggests that Hawaiian L. cuprina may be evolving rapidly. Moreover, the
      monophyly of these flies also suggests that the L. sericata mtDNA haplotype was
      apparently fixed in Hawaiian L. cuprina by lineage sorting, indicating a
      population bottleneck in the evolutionary history of these island flies.

PMID- 11966880
TI  - The D7 family of salivary proteins in blood sucking diptera.
AB  - The D7 subfamily of salivary proteins is widespread in blood sucking Diptera and
      belongs to the superfamily of pheromone/odourant binding proteins. Although D7
      proteins are among the most abundant salivary proteins in adult female mosquitoes
      and sand flies, their role in blood feeding remains elusive. In the present work
      we report the sequence of seventeen novel D7 proteins, and propose an
      evolutionary scenario for the appearance of the several forms of this protein,
      based on a total of twenty-one sequences from Culex quinquefasciatus, Aedes
      aegypti, Anopheles gambiae, An. arabiensis, An. stephensi, An. darlingi
      mosquitoes and Lutzomyia longipalpis and Phlebotomus papatasi sand flies.

PMID- 11966881
TI  - Genetic structure of a greenhouse population of the spider mite Tetranychus
      urticae: spatio-temporal analysis with microsatellite markers.
AB  - The genetic structure of a greenhouse population of the mite Tetranychus urticae
      was studied by the analysis of five microsatellite loci. Genetic variation was
      compared during a crop season between periods of population foundation and rapid
      population increase and was investigated in two consecutive years. The population
      displayed significant heterozygote deficiency at all the sampling periods.
      However, inbreeding tended to decrease with increasing density (FIS coefficient
      between 0.13 and 0.25). No significant genetic differentiation between samples
      was found either at a spatial scale within the greenhouse or at a temporal scale
      between two growing seasons (FST between 0.008 and 0.09). Estimations of the
      genetic relatedness between pairs of individuals indicated that the distances
      between pairs of sisters and unrelated mites in the greenhouse were not
      significantly different, suggesting that mites do not tend to form patches that
      reside close to the point of birth.

PMID- 11966882
TI  - Extrachromosomal RNA-DNA complex containing long telomeric repeats in
      chironomids.
AB  - We have analysed an extracted RNase sensitive fraction containing telomeric
      repeat sequences in the telomerase negative dipteran Chironomus tentans. It shows
      a slow and well-defined electophoretic migration corresponding to > 20 kb and is
      sensitive not only to RNase, but also to DNase. It hybridizes to both strands of
      the telomeric repeat with about equal intensities. DNA is probably the dominant
      component since the fraction is only slightly heavier than genomic DNA in
      isopycnic gradients but considerably lighter than RNA. It can, nevertheless, be
      shown to incorporate tritiated uridine. The material might represent another
      example of extrachromosomal telomeric repeats in telomerase negative cells.

PMID- 11966883
TI  - Amino acids in SRS1 and SRS6 are critical for furanocoumarin metabolism by
      CYP6B1v1, a cytochrome P450 monooxygenase.
AB  - CYP6B1v1 is the principal cytochrome P450 monooxygenase (P450) that detoxifies
      dietary furanocoumarins in the guts of Papilio polyxenes, the black swallowtail
      caterpillar. Sequence alignments and structure comparisons of CYP6B1v1 with the
      mouse CYP2A5 and bacterial CYP102 proteins, which are also capable of
      metabolizing the linear furanocoumarin xanthotoxin (8-methoxypsoralen), suggested
      that Phe116, His117, Val368 and Phe484 might be active site residues. In a
      homology model developed for CYP6B1v1, the side chains of Phe116 and His117
      located in the B'-C loop of SRS1 are predicted to be positioned above the haem
      plane, while the side chain of Phe484 located in SRS6 is predicted near the
      entrance of the catalytic pocket. Site-directed mutagenesis of residues Phe116,
      His117 and Phe484 indicated that these residues represent several of those that
      determine this protein's stability and substrate specificity. Whereas all
      aromatic mutants of Phe116 and Phe484 generated CO-difference spectra with maxima
      at 450 nm indicative of correctly configured monooxygenases, aromatic mutants of
      Phe116 exhibited reduced reactivities toward some furanocoumarins and aromatic
      mutants of Phe484 eliminated all reactivities toward furanocoumarins. All single
      and double aliphatic mutants of Phe116, His117 and Phe484 and aromatic mutants of
      His117 generated carbon monoxide (CO) difference spectra with maxima at 420 nm
      (P420) indicative of incorrectly configured monooxygenases. These studies define
      residues Phe116, His117 and Phe484 as determinants of this insect P450's
      catalytic site integrity and residues Phe116 and Phe484 as determinants of its
      substrate specificity. Conservation of Phe116 and His117 in an array of
      lepidopteran CYP6B proteins implies that these amino acids serve a similar
      function in other monooxygenases of the insect CYP6B subfamily.

PMID- 11966884
TI  - Leveraging genomic databases: from an Aedes albopictus mosquito cell line to the
      malaria vector Anopheles gambiae via the Drosophila genome project.
AB  - An important justification for genome sequencing efforts is the anticipation that
      data from model organisms will provide a framework for the more rapid analysis of
      other, less studied genomes. In this investigation, we sequenced an internal
      region of 25 amino acids from a 52 kDa protein that was differentially expressed
      in 20-hydroxyecdysone-treated Aedes albopictus cells in culture. Within the
      GenBank non-mouse and non-human expressed sequence tag (EST) database, this
      "Aedes peptide" uncovered a putative homology to hypothetical translation
      products from Anopheles gambiae, Caenorhabditis elegans and Drosophila
      melanogaster. The hypothetical translation product from D. melanogaster, which
      included 462 amino acids, uncovered five expressed sequence tags (ESTs) from the
      malaria vector, Anopheles gambiae. When the Anopheles ESTs were aligned against
      the hypothetical Drosophila protein, we found that in aggregate they covered 324
      amino acids, with gaps measuring 19, 30, and 87 amino acids. To approximate the
      complete amino acid sequence, gaps between translation products from Anopheles
      ESTs were replaced with corresponding amino acids from Drosophila to arrive at a
      calculated mass of 51 104 and a pI of 5.84 for the mosquito protein, consistent
      with the position of the Ae. albopictus protein on two-dimensional polyacrylamide
      gels. Finally, tandem mass spectrometry of a tryptic digest of the 52 kDa Ae.
      albopictus protein revealed 33 peptides with masses within 1 Dalton of those
      predicted from an in silico digestion of the reconstructed Anophleles protein. In
      addition to providing the first direct evidence that a hypothetical protein in
      Drosophila is in fact translated, this analysis provides a general approach for
      maximizing recovery, from existing databases, of information that can facilitate
      prioritization of efforts among several candidate proteins.

PMID- 11966885
TI  - Editorial. Protecting the interests of children.

PMID- 11966886
TI  - Administering local anaesthesia to paediatric dental patients -- current status
      and prospects for the future.
AB  - Fear-related behaviours have long been recognized as the most difficult aspect of
      patient management and can be a barrier to good care. Anxiety is one of the major
      issues in the dental treatment of children, and the injection is the most anxiety
      provoking procedure for both children and adults. There is a constant search for
      ways to avoid the invasive, and often painful, nature of the injection, and to
      find more comfortable and pleasant means for anaesthesia before dental
      procedures. OBJECTIVE: The purpose of the present review is to summarize relevant
      data on topics connected with the administration of local anaesthesia. METHODS:
      The review will survey the current available methods, viz. electronic
      anaesthesia, lidocaine patch, computerized anaesthesia (the Wand), and the
      syrijet as well as the conventional injection, used for paediatric patients.
      CONCLUSIONS: Usually new techniques for locally anaesthetizing dental patients
      are tested on adults. However, despite recent research in the field, the
      injection remains the method of choice. It is necessary to continue to conduct
      studies using new techniques on adults and children, so that a more acceptable
      technique can be found.

PMID- 11966887
TI  - Determinants of self-rated oral health status among school children in northern
      Tanzania.
AB  - OBJECTIVE: This study aimed to assess the perceived oral health status and to
      explore its relationship with clinically assessed dental fluorosis among school
      children in Arusha town, Tanzania. METHODS: A total of 478 students (mean age
      15.7 years) completed questionnaires administered in the schools during May to
      July 2000. Clinical photos of the upper and lower incisors were taken under field
      conditions. A total of 461 slides were rated under laboratory conditions. The
      severity of dental fluorosis in the permanent maxillary central incisors was
      assessed using the Thylstrup & Fejerskov Index (TFI). RESULTS: The prevalence of
      dental fluorosis at TFI score > or = 2 was 74%. A total of 67% of boys and 70% of
      girls rated their teeth as yellow to brown, 58% of boys and 68% of girls (P <
      0.05) confirmed dissatisfaction with their dental appearance. Kappa values of
      0.40-0.44 were obtained between dental fluorosis (TFI > or = 2) and self-reported
      discoloration. The proportion of school children reporting dissatisfaction with
      oral condition and dental appearance increased with increasing TFI scores.
      Stepwise multiple logistic regression analysis explained 21% and 32% of the
      variance in the dissatisfaction with oral condition and dental appearance scores;
      TFI scores 11% and 15% of variation in points, and social and psychological
      variables 11% and 17%. CONCLUSION: Whereas dental fluorosis at different
      diagnostic cut-off points impacts self-rated oral health negatively, social and
      personal factors are as important in shaping the responses of school children to
      oral condition and dental appearance.

PMID- 11966888
TI  - Influence of parents' oral health behaviour on oral health status of their school
      children: an exploratory study employing a causal modelling technique.
AB  - OBJECTIVES: The aim of this study was to examine the simultaneous
      interrelationships between parents' oral health behaviour and the oral health
      status of their school children. SAMPLE AND METHODS: Subjects comprised 296 pairs
      of parents (mother or father) and their children at an elementary school in
      Hiroshima. The child's dental examination was performed using the World Health
      Organization (WHO) caries diagnostic criteria for decayed teeth (DT) and filled
      teeth (FT). The Oral Rating Index for Children (ORI-C) was used for the child's
      gingival health examination. Hiroshima University Dental Behavioural Inventory
      (HU-DBI) was used for the assessment of the parents' oral health behaviour. A
      parent-child behavioural model was tested by the linear structural relations
      (LISREL) programme. RESULTS: There was a significant correlation between DT and
      ORI-C (r = - 0.168; P < 0.01). Correlation was found between ORI-C and oral
      health behaviour in children (OHB-C) (r = 0.182; P < 0.01). OHB-C was
      significantly associated with the HU-DBI (r = 0.251; P < 0.001). The hypothesized
      model after some revisions was found to be consistent with the data (chi(2) =
      1.3, d.f. = 6, P = 0.97; Goodness of Fit Index = 0.999). Parents' oral health
      behaviour affected their children's oral health behaviour (P < 0.001). Children's
      oral health behaviour affected their DT through its effect on gingival health
      level. Parents' oral health behaviour also had a significant direct effect on
      their children's DT (P < 0.05). Children's grade affected both DT and their oral
      health behaviour. CONCLUSIONS: Parents' oral health behaviour could influence
      their children's gingival health and dental caries directly and/or indirectly
      through its effect on children's oral health behaviour.

PMID- 11966889
TI  - Prostaglandin E2 and treatment outcome in pulp therapy of primary molars with
      carious exposures.
AB  - OBJECTIVES: Prostaglandin E2 (PGE2) has been suggested as an indicator of
      irreversible pulpitis in permanent teeth [1]. There is scant information on the
      role of chemical mediators in primary molar pulp inflammation. The aim of this
      preliminary study was to investigate the levels of PGE2 in blood harvested from
      root pulp stumps following coronal pulp amputation in vital primary molar teeth
      with carious exposures. METHODS: Seventy-nine cariously exposed primary molars
      underwent treatment by one of two vital pulp therapy techniques. Blood was
      harvested from 38 teeth and volume and concentration of PGE2 ([PGE2]) determined
      [2]. Treatment outcome was assessed from both clinical and radiographic evidence.
      RESULTS: PGE2 was detected in all samples, with a wide concentration range (1
      2641 ng/mL). The distribution was skewed, requiring log transformation. The
      difference in the mean (log) [PGE2] for radiological success (3.12, SD 1.60 and
      failure (4.62, SD 1.80) was significant, t = 2.05, P = 0.047. The difference in
      the mean (log) [PGE2] for clinical success (3.24, SD 1.65) and failure (5.44, SD
      1.43 was near-significant, t = 1.84, P = 0.074. CONCLUSION: [PGE2] correlated
      positively with radiological outcome following vital pulp therapy.

PMID- 11966890
TI  - Knowledge, attitudes and status of oral health in children at risk for infective
      endocarditis.
AB  - AIM: The purpose of this study was to assess the oral health status of 104
      children (2-17 years of age) at risk for infective endocarditis attending the
      Paediatric Cardiology Service of the Martagao Gesteira Institute of Child Care
      and Paediatrics, Rio de Janeiro, Brazil, and their guardians' attitudes towards
      and knowledge about endocarditis risks. METHODS: A structured interview was
      carried out with guardians and an oral examination was performed on each child to
      determine scores for the plaque index (PI), gingival index (GI) and dmft/DMFT
      index. RESULTS: The percentage of guardians who understood the meaning of 'heart
      infection' was 9.6%, who knew the possibility of heart disease caused by dental
      procedures was 60.6%, who understood the requirement for antibiotic cover before
      dental treatment was 72.1%, and who understood the importance of good oral health
      to prevent infective endocarditis was 41.3%. As regards oral health behaviours,
      46.1% of children brushed their teeth three times or more a day, 28.8% had never
      visited a dentist before, and only 24.3% attended the dentist for prevention.
      There was visible plaque in 98% and gingival bleeding in 99% of children in this
      study. The caries experience for primary dentition (dmft) was 2.62%, and 3.97 for
      permanent dentition (DMFT). CONCLUSIONS: Based on these results, we can conclude
      that the guardians' knowledge and attitudes about oral health were not good. This
      group at risk has poor oral health, which may give rise to a frequent bacteraemia
      under physiological conditions.

PMID- 11966891
TI  - Caries risk analysis: considering caries as an individual time-dependent process.
AB  - AIM: To estimate the probability that a tooth does not develop a cavitated lesion
      (= end-stage caries) within time periods of interest. Additionally it was of
      interest to assess the heterogeneity between patients, in relation to the time
      periods required for their teeth to develop a cavitated lesion. DESIGN: A
      prospective study using patient data of a clinical pedodontic course. SAMPLE AND
      METHODS: Forty-one patients who had been followed for at least 3 years were
      selected. Before initiation of therapy, affiliation to a specific risk group was
      checked. Nine individuals who had belonged to a high-risk group on test were
      excluded. Of 1968 teeth, 1378 were eligible for data evaluation. The statistical
      techniques applied originate from time-to-event analysis methods, including a
      parametric frailty approach providing estimates of the relative caries risk for
      each individual to develop a cavitated lesion. RESULTS: In the selected group of
      patients the probability that a tooth remained free of a cavitated lesion within
      five years ranged from 0.89 to 0.95 applying a 95% confidence interval. In the
      present sample the true caries risk of the patients to develop a cavitated lesion
      varied considerably although such variation was not expected from the individual
      examinations at baseline. CONCLUSION: The frailty model accounts sufficiently for
      the heterogeneity of each patient. The applied time-to-event methods facilitated
      reliable estimation of both the probability that a tooth remains free of a
      cavitated lesion within a certain time and the relative caries risk of an
      individual to develop a cavitated lesion.

PMID- 11966892
TI  - Sequential development of multiple supernumerary teeth in the mandibular premolar
      region -- a radiographic case report.
AB  - This report presents a case of multiple supernumerary teeth developing in the
      mandibular premolar region in an Asian female patient. A series of radiographs
      taken over a 10-year period, demonstrate the sequential development of these
      teeth during the patient's early and middle teenage years. The importance of
      regular radiographic review and appropriate management for such cases is
      discussed.

PMID- 11966893
TI  - Three-year clinical performance of glass ionomer cement in primary molars.

PMID- 11966896
TI  - UK National Clinical Guidelines in Paediatric Dentistry. Extraction of primary
      teeth -- balance and compensation.

PMID- 11966898
TI  - A review: malolactic fermentation in wine -- beyond deacidification.

PMID- 11966899
TI  - Selenium incorporation into Saccharomyces cerevisiae cells: a study of different
      incorporation methods.
AB  - AIMS: To study the effects of the selenium enrichment protocols in yeast at
      various points in the cell cycle, total selenium accumulation and the forms of
      selenium incorporated. METHODS AND RESULTS: The use of selenized yeast as
      enriched selenium supplements in human nutrition has become a topic of increasing
      interest over the last decade. Four enrichment procedures have been evaluated
      using sodium selenite as the selenium source: enrichment during the growth phase;
      enrichment at the non-growth phase, both of these at different selenium levels;
      enrichment by seeding in a fermentable carbon source (glucose); Se-enrichment
      with a non-fermentable carbon source (glycerol). A nitric acid digestion of the
      yeast samples prepared under different conditions has been performed in order to
      evaluate the total selenium incorporated into the yeast cells. Also, an enzymatic
      digestion of the yeast samples with pepsin has been carried out as an initial
      step to begin the process of determining which of the different possible selenium
      species are formed. The cell count evaluations of the selenium-enriched yeast
      showed that the growth phase, seeding and the use of YEPG media is influenced by
      the addition of Se, while the non-growth phase is not. Total selenium
      incorporation studies showed that seeding the yeast permits more accumulation of
      selenium. Speciation studies of the enriched yeast showed that the growth phase
      increases the formation of L-Se-methionine. CONCLUSIONS: When the aim of
      enriching yeast with selenium is the formation of L-Se-methionine, the best
      enrichment procedure is using the growth phase with small concentrations of
      sodium selenite. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of selenium
      supplements is widespread and most of the supplements use selenium-enriched yeast
      in their formulation. Studies made on supplements do not have the appropriate Se
      species for optimal absorption in the human body. This study presents and
      compares methods for the best selenium yeast enrichment that could ultimately be
      used in selenium supplement formulations.

PMID- 11966900
TI  - Production of biogenic amines and divercin V41 in cold smoked salmon inoculated
      with Carnobacterium divergens V41, and specific detection of this strain by
      multiplex-PCR.
AB  - AIMS: The objective of this study was to determine the technological behaviour
      (implantation and biogenic amines production) of Carnobacterium divergens V41, an
      anti-Listeria bacteriocin producer (divercin V41), after inoculation in cold
      smoked salmon (CSS). METHODS AND RESULTS: Implantation of the strain was followed
      by multiplex-PCR during 27 days of storage at 4 degrees C, and biogenic amines
      were quantified by HPLC. It was found that the strain was able to develop quite
      well in CSS among lactic wild flora. Divercin V41 (400 AU ml-1) was produced in
      CSS, and the biogenic amine content was not modified by inoculation of the
      bacteria. CONCLUSIONS: Carnobacterium divergens V41 is a safe, interesting,
      bioprotective agent. SIGNIFICANCE AND IMPACT OF THE STUDY: This strain could
      potentially be used for efficient prevention of L. monocytogenes growth in CSS.

PMID- 11966901
TI  - Factors influencing the susceptibility of Gram-negative bacteria to toluidine
      blue O-mediated lethal photosensitization.
AB  - AIMS: Bacteria can be killed by red light in the presence of a photosensitizer.
      The purpose of this study was to evaluate the effect of physiological and
      environmental factors on the susceptibility of some bacteria associated with oral
      infections in immunocompromised patients to killing by the photosensitizer
      toluidine blue O (TBO). METHODS AND RESULTS: Suspensions of Pseudomonas
      aeruginosa, Escherichia coli and Klebsiella pneumoniae in human saliva, horse
      serum or saline were exposed to light from a helium/ neon laser in the presence
      of TBO. Additional suspensions at various growth phases and pHs were treated in
      an identical manner. Survivors were enumerated by viable counting. All three
      species were susceptible to lethal photosensitization under all of the conditions
      tested. The presence of serum and, to a lesser extent, saliva decreased the level
      of kill attained. The bactericidal effect was reduced at acid pHs but was
      unaffected by the growth phase of the organism. CONCLUSIONS: The composition and
      pH of the fluid in which bacteria are suspended influenced the effectiveness of
      TBO-mediated lethal photosensitization, whereas killing was unaffected by the
      growth phase of the organism. SIGNIFICANCE AND IMPACT OF THE STUDY: Environmental
      factors operating in the mouths of patients with mucositis could reduce the
      effectiveness of TBO-mediated lethal photosensitization of bacteria associated
      with this condition.

PMID- 11966903
TI  - A reverse transcriptase-polymerase chain reaction assay for detection of viable
      Escherichia coli O157:H7: investigation of specific target genes.
AB  - AIMS: To determine suitable target genes for detection of the pathogen
      Escherichia coli O157:H7 by reverse transcriptase-polymerase chain reaction (RT
      PCR). METHODS AND RESULTS: Potential genes used as indicators for viability
      included rfbE, fliC, stx1, stx2, mobA, eaeA, hly and 16S rRNA. Under normal
      growth conditions, rfbE, stx1, hly and 16S rRNA amplicons were detected in
      association with all growth phases. The products of 16S rRNA, mobA, rfbE and stx1
      were readily visualized in RNA isolated from viable but non-culturable cells. The
      16S rRNA gene was not amplified following heat treatment of cells at 121 degrees
      C for 15 min and mRNA targets were not amplified after treatment at 60 degrees C
      for 20 min. In this instance, genes that are not amplified are good targets for
      determining viability. CONCLUSIONS: The results of RT-PCR amplification indicate
      that, under the conditions examined, the rfbE gene is the most appropriate target
      for detection of viable E. coli O157:H7. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Prior to detection or identification from an environmental or food sample E. coli
      O157:H7 may be exposed to many harsh conditions that influence nucleic acid (RNA
      and DNA) stability. This study gives an insight into the effects of temperature
      and nutrient deprivation on identification of viable cells using RT-PCR. It also
      suggests that, if RT-PCR is to be used for detection of live cells in a sample
      without enrichment, 10(7) cfu of the target organism are required.

PMID- 11966902
TI  - In vitro control of growth and fumonisin production by Fusarium verticillioides
      and F. proliferatum using antioxidants under different water availability and
      temperature regimes.
AB  - AIMS: To examine the effect of butylated hydroxyanisole (BHA), butylated
      hydroxytoluene (BHT), trihydroxybutyrophenone and propylparaben (PP) (at
      concentrations of 1-20 mmol l(-1)) on growth of and fumonisin production by
      Argentinian strains of Fusarium verticillioides and F. proliferatum. METHODS AND
      RESULTS: Studies on lag phases prior to growth, relative growth rates and
      fumonisin concentrations were carried out in vitro in relation to water activity
      (0.995-0.93 a(w)) and temperature (18 and 25 degrees C) on a maize meal agar.
      Overall, PP was the antioxidant which was most effective at inhibiting strains of
      both species. The lag phase prior to growth and growth rates were significantly
      decreased by PP and BHA at 10 and 20 mmol l(-1), regardless of the temperature or
      aw level tested. Total fumonisin production was higher at 0.98 a(w) and decreased
      by about 45-50% at 0.995 and 0.95 a(w). Overall, BHT only inhibited fumonisin
      production at 0.95 aw at 10 and 20 mmol l(-1), while BHA was effective at most
      a(w) levels tested at 10 and 20 mmol l(-1). Propylparaben completely inhibited
      fumonisin production by both F. verticillioides and F. proliferatum at > 1 mmol
      l(-1), regardless of the temperature or a(w) level. Small interstrain differences
      in the levels of inhibition by the antioxidants were observed for three F.
      verticillioides and four F. proliferatum strains at 0.995, 0.98 and 0.95 a(w).
      Propylparaben and BHA completely inhibited the growth of both species at the
      concentrations evaluated, regardless of the a(w) level. CONCLUSIONS: Two
      antioxidants show promise for the control of growth of and fumonisin production
      by these species over a wide range of environmental conditions. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Potential exists for using such food-grade preservatives for
      prevention of mycotoxigenic fungi and their toxins entering the food chain.

PMID- 11966904
TI  - Combining chlorination and chloramination processes for the inhibition of biofilm
      formation in drinking surface water system models.
AB  - AIMS: The aim of this study was to investigate the inhibition of biofilm
      formation on stainless steel (SS) and galvanized mild steel (MS) in chlorine
      (AFC(1)) and chlorine-monochloramine treated waters (AFC(2)M). METHODS AND
      RESULTS: Disinfection was carried out using 2.5 mg l(-1) free chlorine followed
      by 1.5 mg l(-1) monochloramine, with non-disinfected water used as control water.
      Results of the standard spread plate procedure, DAPI epifluorescence microscopy
      and scanning electron microscopy revealed bacterial colonization of SS and MS
      exposed to non-disinfected and chlorinated waters between 24 and 720 h, while no
      bacterial adhesion was detected on SS and MS exposed to AFC(2)M between 48 and
      504 h. CONCLUSIONS: The inability of bacteria to grow on SS and MS was observed
      only when 0.35 mg l(-1) residual monochloramine was maintained throughout the
      system. SIGNIFICANCE AND IMPACT OF THE STUDY: This demonstrates the inability of
      chlorine alone to inhibit bacterial growth and suggests a combination of chlorine
      and monochloramine as a more effective treatment for drinking water, especially
      for rural communities with very poor source waters in Africa.

PMID- 11966905
TI  - Concentration of Cryptosporidium, microsporidia and other water-borne pathogens
      by continuous separation channel centrifugation.
AB  - AIMS: The aim of this study was to determine the effectiveness of continuous
      separation channel centrifugation for concentrating water-borne pathogens of
      various taxa and sizes. METHODS AND RESULTS: Cryptosporidium parvum oocysts,
      Giardia lamblia cysts, Encephalitozoon intestinalis spores and Escherichia coli
      were seeded into different water matrices at densities ranging from 5 to 10 000
      organisms l(-1) and recovered using continuous separation channel centrifugation.
      All pathogens were enumerated on membrane filters using microscopy. Recovery
      efficiencies were usually > 90%. Oocyst recovery did not vary with source water
      turbidity or with centrifuge flow rate up to 250 ml min(-1). Based on
      excystation, this concentration method did not alter oocyst viability.
      CONCLUSIONS: Continuous separation channel centrifugation is an effective means
      of concentrating water-borne pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Methods are needed for detecting pathogens in drinking water to ensure public
      health. The first step for any pathogen detection procedure is concentration.
      However, this step has been problematic because recovery efficiencies of
      conventional methods, like filtration, are often low and variable, which may lead
      to false negatives. Continuous separation channel centrifugation can
      simultaneously concentrate multiple pathogens as small as 1 microm with high and
      reproducible efficiency in a variety of water matrices.

PMID- 11966906
TI  - Distribution of genotypes of F-specific RNA bacteriophages in human and non-human
      sources of faecal pollution in South Africa and Spain.
AB  - AIMS: To assess whether the distribution of genotypes of F-specific RNA
      bacteriophages reflects faecal pollution of human and animal origin in water
      environments. METHODS AND RESULTS: Stool samples, animal feedlot waste slurries
      and a wide variety of faecally polluted waters were studied in South Africa and
      Spain. Genotyping was performed by plaque and spot hybridization with genotype
      specific probes. Only genotypes II and III were detected in human stool. Animal
      faeces contained predominantly, but not exclusively, genotypes I and IV. Raw
      hospital and municipal sewage contained mostly genotypes II and III, whereas
      genotypes I and II prevailed in settled sewage, secondary treated sewage and non
      point diffuse effluents from developing communities. Abattoir wastewaters
      contained mostly genotypes I and IV. No differences were observed between the
      distribution of genotypes in Spain and South Africa. CONCLUSIONS: Although the
      association of genotypes II and III with human excreta and I and IV with animal
      excreta was statistically significant, the results suggest that the association
      cannot be used for absolute distinction between faecal pollution of human and
      animal origin. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributes
      greatly to understanding the usefulness of genotypes of F-specific RNA
      bacteriophages in source tracking of faecal wastes.

PMID- 11966907
TI  - Combined effects of chemical, heat and ultrasound treatments to kill Salmonella
      and Escherichia coli O157:H7 on alfalfa seeds.
AB  - AIMS: To determine the effectiveness of combined treatments with chemicals, heat
      and ultrasound in killing or removing Salmonella and Escherichia coli O157:H7 on
      alfalfa seeds intended for sprout production. METHODS AND RESULTS: Alfalfa seeds
      inoculated with Salmonella or E. coli O157:H7 were treated with ultrasound (38.5
      40.5 kHz) in solutions containing 1% Ca(OH)(2), 1% Tween 80, 1% Ca(OH)(2) plus 1%
      Tween 80, 160 microg ml(-1) Tsunami 200 and 0.5% Fit at 23 and 55 degrees C for 2
      and 5 min. Highest reductions were in chemical solutions at 55 degrees C, but
      seed viability was also reduced compared with treatment at 23 degrees C.
      Inactivation of Salmonella and E. coli O157:H7 was generally enhanced by
      simultaneous treatments with ultrasound, chemicals and heat. CONCLUSIONS:
      Ultrasound treatment, in combination with chemicals and heat, had a modest
      enhancing effect on the effectiveness of chemicals in killing or removing
      pathogens on alfalfa seeds. Overall, treatment with 1% Ca(OH)(2) was most
      effective in killing Salmonella and E. coli O157:H7. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The use of 1% Ca(OH)(2) instead of 20,000 microg ml(-1) chlorine,
      which is currently recommended as a sanitizer for seeds intended for sprout
      production in the US, should be considered. Ultrasound treatment of alfalfa seeds
      containing Salmonella or E. coli O157:H7, in combination with chemical treatment,
      contributes to achieving greater reductions in populations of these pathogens,
      thereby reducing the risk of contamination and the presence of pathogens in
      sprouts produced from these seeds.

PMID- 11966908
TI  - Studies on the mechanisms of the sporicidal action of ortho-phthalaldehyde.
AB  - AIMS: To determine the mechanism of killing of spores of Bacillus subtilis by
      ortho-phthalaldehyde (OPA), an aromatic dialdehyde currently in use as an
      antimicrobial agent. METHODS AND RESULTS: OPA is sporicidal, although spores are
      much more OPA resistant than are vegetative cells. Bacillus subtilis mutants
      deficient in DNA repair, spore DNA protection and spore coat assembly have been
      used to show that (i) the coat appears to be a major component of spore OPA
      resistance, which is acquired late in sporulation of B. subtilis at the time of
      spore coat maturation, and (ii) B. subtilis spores are not killed by OPA through
      DNA damage but by elimination of spore germination. Furthermore, OPA-treated
      spores that cannot germinate are not recovered by artificial germinants or by
      treatment with NaOH or lysozyme. CONCLUSIONS: OPA appears to kill spores by
      blocking the spore germination process. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This work provides information on the mechanism of spore resistance to, and spore
      killing by, the disinfectant, OPA.

PMID- 11966909
TI  - Use of a novel method to characterize the response of spores of non-proteolytic
      Clostridium botulinum types B, E and F to a wide range of germinants and
      conditions.
AB  - AIMS: Limited information is available on the germination triggers for spores of
      non-proteolytic Clostridium botulinum. An automated system was used to study the
      effect of a large number of potential germinants, of temperature and pH, and
      aerobic and anaerobic conditions, on germination of spores of non-proteolytic Cl.
      botulinum types B, E and F. METHODS AND RESULTS: A Bioscreen analyser was used to
      measure germination by decrease in optical density. Results were confirmed by
      phase-contrast light microscopy. Spores of strains producing type B, E and F
      toxin gave similar results. Optimum germination occurred in L-alanine/L-lactate,
      L-cysteine/L-lactate and L-serine/L-lactate (50 mmol l(-1) of each). A further 12
      combinations of factors induced germination. Sodium bicarbonate, sodium
      thioglycollate and heat shock each enhanced germination, but were not essential.
      Germination was similar in aerobic and anaerobic conditions. The optimum pH range
      was 5.5-8.0, germination occurred at 1-40 degrees C, but not at 50 degrees C, and
      was optimal at 20-25 degrees C. CONCLUSIONS: The automated system enabled a
      systematic study of germination requirements, and provided an insight into
      germination in spores of non-proteolytic Cl. botulinum. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The results extend understanding of germination of non-proteolytic
      Cl. botulinum spores, and provide a basis for improving detection of viable
      spores.

PMID- 11966910
TI  - Widespread distribution of the bacteriocin-producing lactic acid cocci in Miso
      paste products.
AB  - AIMS: A survey was conducted on the ecological distribution of bacteriocin
      producing lactic acid bacteria in Miso-pastes, a typical fermented food in Japan.
      METHODS AND RESULTS Nine Miso-pastes were sampled for isolation of bacteriocin
      producers. Almost all isolated enterococcal strains produced bacteriocins but no
      isolated tetragenococci did so. The bacteriocin-producing isolates were divided
      into nine groups by phenotypic tests. As the phenotypic characters were highly
      diverse, these strains could not be identified to species level on the basis of
      their phenotypes. The nine representative strains from each group were identified
      by 16S rRNA analysis. These bacteriocin-producers with one exception (Lactococcus
      sp.) were identified as strains of the Enterococcus faecium 'species group'. The
      bacteriocins of the nine strains were classified into five types according to
      their antibacterial spectral patterns and their SDS-PAGE profiles. The
      bacteriocins inhibited undesirable bacteria in Miso-pastes, such as Bacillus
      subtilis, but did not inhibit the useful Tetragenococcus halophila. CONCLUSIONS:
      The bacteriocin-producing lactic acid cocci were widespread at high frequencies
      in Miso-pastes. They were considered to play an important role in preventing the
      growth of undesirable bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      suggests that bacteriocin-producers act effectively as safe biopreservatives and
      may contribute to the biopreservation in Miso-pastes.

PMID- 11966911
TI  - Stimulation of Alexandrium fundyense growth by bacterial assemblages from the Bay
      of Fundy.
AB  - AIMS: To evaluate the influence of marine bacterial assemblages from the Bay of
      Fundy on Alexandrium fundyense str. CB301 growth. METHODS AND RESULTS: Bacterial
      assemblages were collected from the Bay of Fundy during an Alexandrium spp.
      bloom, serially diluted to extinction and inoculated into axenic CB301 cultures.
      Bacterial assemblages dramatically enhanced CB301 growth. Retrieval and analysis
      of 16S rDNA fragments revealed an Alteromonas sp. strain to be the only
      detectable bacterium in all assemblages that promoted A. fundyense and the sole
      bacterium found in the most dilute inoculum that promoted A. fundyense. While
      this bacterium has not yet been isolated, other isolates obtained from the
      assemblages did not stimulate A. fundyense, indicating that the observed
      stimulation was not a general effect of marine bacteria. CONCLUSIONS: Bay of
      Fundy marine bacterial assemblages dominated by a member of the family
      Alteromonadaceae were found to dramatically stimulate growth of A. fundyense.
      SIGNIFICANCE AND IMPACT OF THE STUDY: These results show that native bacteria
      have the potential to dramatically promote the growth of A. fundyense and may
      play an important role in influencing A. fundyense dynamics in the Bay of Fundy.

PMID- 11966912
TI  - Campylobacter hyointestinalis subsp. hyointestinalis, a common Campylobacter
      species in reindeer.
AB  - AIMS: To study the prevalence of Campylobacter spp. in the faecal material of
      reindeer, and to identify the isolates by means of a polyphasic approach. In
      addition, to study the genetic diversity of Camp. hyointestinalis subsp.
      hyointestinalis reindeer isolates by pulsed-field gel electrophoresis (PFGE).
      METHODS AND RESULTS: The material, collected during the slaughter period in
      autumn 1998, comprised 399 faecal contents from the reindeer (Rangifer tarandus),
      a semi-domesticated, meat-producing ruminant of northern Finland. These samples
      came from 16 herds in the areas of eight reindeer slaughterhouses. Samples were
      cultured by methods suitable for isolation of fastidious Campylobacter species.
      Of all samples, 6% (24/399) were Campylobacter-positive. Phenotypic
      characteristics, SDS-PAGE protein patterns, dot blot DNA-DNA hybridization, 23S
      rDNA restriction fragment polymorphism analysis and PFGE identified the isolates
      as Camp. hyointestinalis subsp. hyointestinalis. CONCLUSIONS: Campylobacter
      hyointestinalis subsp. hyointestinalis was the only Campylobacter species
      isolated from reindeer in this study. The isolates showed high genomic diversity
      in PFGE with the restriction enzymes SmaI and KpnI. SIGNIFICANCE AND IMPACT OF
      THE STUDY: PFGE analysis is a useful subtyping method for epidemiological
      studies. Contaminated reindeer meat can be a source for human infections.

PMID- 11966913
TI  - Evaluation of a selective medium for Brucella isolation using natamycin.
AB  - AIMS: To select an anti-fungal agent to replace cycloheximide in the media used
      for isolation of Brucella. METHODS AND RESULTS: One potential agent, natamycin,
      was evaluated using 28 Brucella isolates, 18 yeasts and 14 fungi. The material
      for the evaluation included 37 bovine milk samples, six bovine vaginal swabs and
      45 milk samples artificially infected with Brucella. The recovery of Brucella
      only from the artificially-inoculated milk samples increased with the use of the
      medium containing natamycin instead of cycloheximide, at the same time
      significantly inhibiting the growth of yeasts, fungi and other bacteria. The
      inclusion of either anti-fungal agent allowed growth of the 28 Brucella isolates
      and totally prevented the growth of all 18 yeasts and 13 of the 14 fungi.
      CONCLUSIONS: Based on the results it was concluded that natamycin would be a
      suitable alternative to cycloheximide. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Cycloheximide has become unavailable worldwide and is currently an anti-fungal
      constituent of the medium often used for isolation of Brucella organisms. The use
      of natamycin as a replacement in the formulation did not inhibit growth of
      Brucella and was effective at eliminating most contaminants.

PMID- 11966914
TI  - Antimicrobial susceptibility changes and T-OMP shifts in pyrithione-passaged
      planktonic cultures of Pseudomonas aeruginosa PAO1.
AB  - AIMS: The aim of this study was to determine whether passaging Pseudomonas
      aeruginosa PAO1 with sub-MICs of the pyrithione biocides results in both the
      induction of decreased susceptibility towards these antimicrobials and associated
      outer membrane profile changes. METHODS AND RESULTS: Previous work by this group
      has shown that it is possible to induce susceptibility changes towards the
      isothiazolone biocides in Ps. aeruginosa PAO1 by successive passages in the
      presence of increasing sub-MICs of biocide. This procedure was accompanied by the
      loss of a 35 kDa outer membrane protein, T-OMP. In this experiment, this process
      was repeated with the biocides sodium pyrithione (NaPT), zinc pyrithione (ZnPT)
      and cetrimide. The pattern of susceptibility was similar to that observed with
      the isothiazolone biocides. Upon removal of biocide, the observed MIC did not
      return to the original pre-exposure value. The onset and development of
      resistance was accompanied by the loss of T-OMP from outer membrane profiles,
      which suggests that this is a non-specific membrane channel whose production
      within the cell is sensitive to biocide presence. The T-OMP reappeared when the
      cells were passaged in the absence of pyrithione. Cross-resistance studies
      indicated that induced resistance to one biocide yields partial resistance
      towards other members of the group and the positive control. CONCLUSIONS: These
      results indicate that the pyrithione biocides have similar susceptibility
      profiles in Ps. aeruginosa to those exhibited by the isothiazolones, but that the
      acquired changes in susceptibility to the pyrithiones is largely irreversible.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicates that acquired
      susceptibility changes towards sub-MICs of selected biocides are multifactorial
      in nature.

PMID- 11966915
TI  - Yarrowia lipolytica as a potential producer of citric acid from raw glycerol.
AB  - AIMS: To study the biochemical response of Yarrowia lipolytica LGAM S(7)1 during
      growth on raw glycerol (the main by-product of bio-diesel production units) in
      order to produce metabolic products of industrial significance. METHODS AND
      RESULTS: Yarrowia lipolytica was cultivated on raw glycerol or glucose in flasks.
      Although nitrogen-limited media were employed, growth was not followed by
      production of reserve lipid. Nitrogen limitation led to citric acid excretion.
      Growth and citric acid production parameters on glycerol were similar to those
      obtained on glucose. When high initial glycerol media were used, citric acid up
      to 35 g l(-1) (yield 0.42-0.44 g acid g(-1) glycerol consumed) was produced.
      CONCLUSIONS: Raw glycerol was an adequate substrate for Y. lipolytica. Growth was
      not followed by reserve lipid accumulation, but amounts of citric acid were
      produced. SIGNIFICANCE AND IMPACT OF THE STUDY: Raw glycerol is an industrial
      feedstock appearing in increasing quantities as the main by-product of bio-diesel
      production facilities. The present study describes an alternative way of glycerol
      valorization, with the production of remarkable amounts of citric acid, in
      addition to its main valorization way (production of 1,3-propanediol by
      bacteria).

PMID- 11966916
TI  - Contents of cry genes and insecticidal toxicity of Bacillus thuringiensis strains
      from terrestrial and aquatic habitats.
AB  - AIMS: Two Bacillus thuringiensis collections from terrestrial and aquatic
      habitats were compared in order to study the possible interrelationships between
      habitat and biological characteristics (serovar, cry genes content and toxicity).
      METHODS AND RESULTS: Bacillus thuringiensis strains were characterized by
      serology, PCR, and one-dose treatment against the noctuids Helicoverpa armigera
      and Spodoptera exigua, and the dipteran Tipula oleracea. A total of 12 and 10
      different serovars were identified within terrestrial and aquatic strains,
      respectively. The number of non-toxic strains was greater in aquatic (41.6%) than
      in terrestrial habitats (5.3%). The genes cry1C, cry1D and cry1E were
      significantly more frequent in the terrestrial habitat. The cry1B gene was very
      frequent within thuringiensis strains. CONCLUSIONS: A high diversity was found in
      terms of serovars present and cry genes content in both collections. The relative
      frequency of individual cry genes was different in both collections, and a
      serovar-dependent distribution of the cry1B gene was found. Some strains sharing
      the same set of cry genes differed in their toxicity, suggesting important
      differences in gene expression. SIGNIFICANCE AND IMPACT OF THE STUDY: The inter
      relationships between serology, cry gene content and toxicity may allow a better
      understanding of B. thuringiensis ecology.

PMID- 11966917
TI  - Enumeration of Megasphaera elsdenii in rumen contents by real-time Taq nuclease
      assay.
AB  - AIMS: To develop a real-time Taq nuclease assay (TNA) to enable the in vivo
      enumeration of Megasphaera elsdenii. METHODS AND RESULTS: Megasphaera elsdenii
      YE34 was phenotypically characteristic of the species and had 16S rDNA sequence
      similarity of 98% to previously described isolates. Calibration of the number of
      cells of M. elsdenii against the cycle threshold of fluorescent dye release gave
      a straight-line relationship with a correlation coefficient approximating unity.
      The specificity of the assay for M. elsdenii was confirmed by performing it
      against a panel of 24 heterogeneous, mainly ruminal bacteria. Megasphaera
      elsdenii was not detected in ruminal contents from a pasture-fed steer but was
      readily detected 2 and 50 h after the probiotic introduction of the bacterium
      into the rumen. CONCLUSIONS: Real-time TNA has provided a sensitive and specific
      means of enumerating the M. elsdenii population in rumen contents. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Megasphaera elsdenii is an important lactate-degrading
      ruminal bacterium that has been selected for probiotic use to prevent acidosis
      and enhance starch utilization in grain-fed cattle. The assay developed in this
      study provides a tool for determining the ability of probiotically-introduced M.
      elsdenii to establish useful populations in the rumen.

PMID- 11966918
TI  - A note: gut bacteria produce components of a locust cohesion pheromone.
AB  - AIMS: Faecal pellets from germ-free locusts were used as culture media to
      determine the ability of locust gut bacteria to synthesize phenolic components of
      the locust cohesion pheromone. METHODS AND RESULTS: Inoculation of germ-free
      faecal pellets with Pantoea agglomerans, a species commonly isolated from
      locusts, resulted in the release of large amounts of guaiacol and small amounts
      of phenol, both of which are components of the locust cohesion pheromone. Two
      other locust-derived species, Klebsiella pneumoniae pneumoniae and Enterobacter
      cloacae, also produced guaiacol from germ-free faecal pellets, but the
      opportunistic locust pathogen, Serratia marcescens, did not. The most likely
      precursor for guaiacol is the plant-derived vanillic acid, which is present in
      large amounts in the faeces of both conventional and germ-free locusts.
      CONCLUSIONS: These observations are consistent with previous ones, that locust
      gut bacteria are responsible for the production of components of the locust
      cohesion pheromone. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings
      illustrate how an insect can adapt to make use of a common bacterial metabolite
      produced by one or more of its indigenous gut bacterial species. This observation
      has implications for our appreciation of insect gut microbiota interactions.

PMID- 11966919
TI  - Evolution of extracellular enzyme activities during manure composting.
AB  - AIMS: The objectives of this work were to determine the extracellular enzyme
      profiles during composting, relate the activities of these enzymes to the changes
      in microbial population and compare the enzyme profiles between two manures.
      METHODS AND RESULTS: API ZYM assay was used to monitor the activities of 19
      extracellular enzymes during poultry and pig manure composting. Results showed an
      overall increase in diversity and relative abundance of enzymes present. The
      relative abundance and activities of enzymes were higher in poultry manure than
      in pig manure. Among the 19 enzymes tested, esterase, valine amino-peptidase and
      alpha-galactosidase were the most abundant enzymes in poultry manure, whereas it
      was N-acetyl-beta-glucosaminidase for the pig manure. A number of these enzymes
      correlated with change in numbers of different microbial groups during
      composting. CONCLUSIONS: The composting process represented a combined activity
      of a wide succession of environments, as one enzyme/microbial group overlapped
      the other and each emerged gradually due to the continual change in temperature
      and progressive breakdown of complex compounds to simpler ones. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The results presented here show the applicability of the API
      ZYM test not only in monitoring the quantitative and qualitative fluctuation of
      the available substrate during composting, but also in revealing differences in
      composts and compost maturity.

PMID- 11966920
TI  - The influence of nutritional and environmental conditions on the accumulation of
      poly-beta-hydroxybutyrate in Bacillus mycoides RLJ B-017.
AB  - AIMS: To optimize the nutritional and environmental conditions for growth of and
      poly-beta-hydroxybutyrate (PHB) accumulation in Bacillus mycoides RLJ B-017.
      METHODS AND RESULTS: An isolate, identified as B. mycoides, was grown on
      different sources of carbon and nitrogen. Among these, sucrose, beef extract and
      di-ammonium sulphate were found to be the most suitable for growth and PHB
      accumulation. The overall maximum value of PHB (%) in cells, PHB yield (Yp/s) and
      productivities (Qp and qp) were 69.4 +/- 0.4% dry cell weight (DCW), 0.21 gp gS(
      1), 0.104 +/- 0.012 gp l(-1) h(-1) and 0.03 gp gx(-1) h(-1), respectively when
      grown in a medium containing 20 gs l(-1) sucrose, supplemented with di-ammonium
      sulphate. The addition of beef extract increased the value of PHB (%) in cells,
      PHB yield and productivities by 17.58 +/- 0,3, 23.8, 19.23 +/- 0.3 and 13.8 +/-
      0.2% , respectively. The overall maximum values of PHB (% DCW), PHB yield and
      productivities were obtained at pH 7.0 +/- 0 .1, temperature 30 +/- 0.5 degrees
      C, agitation 650 rev min(-1) and oxygen transfer rate 3.8 mmol O(2) l(-1) h(-1).
      CONCLUSIONS: Sucrose, glucose and fructose were found to be more suitable for
      cell growth and PHB accumulation, but sucrose was less expensive than glucose.
      Among the nitrogen sources, beef extract and di-ammonium sulphate promoted PHB
      synthesis. The accumulation of PHB was observed to be growth associated.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Gram-positive bacteria have not been
      reported to accumulate large amounts of polyhydroxyalkanoate and hence have not
      been considered as potent candidates for industrial production. A number of
      Bacillus spp. have been reported to accumulate 9-44.5% DCW PHB. By comparison,
      Bacillus RLJ B-017 contained 69.4 +/- 0.4% DCW PHB. Therefore, this strain has
      been considered as a potent organism for industrial interest. A relatively high
      yield of PHB was obtained in this wild strain and PHB synthesis was independent
      of nutrient limitation. The conditions for the higher PHB yield and productivity
      will be optimized in the next phase using fed-batch culture.

PMID- 11966921
TI  - A rapid method for assessing the suitability of quenching agents for individual
      biocides as well as combinations.
AB  - AIMS: To develop a novel, rapid method for testing the ability of quenching
      agents to neutralize disinfectants. METHODS AND RESULTS: Tests were performed to
      determine the suitability of different neutralizers for a range of disinfectants,
      using a new method based on the Bioscreen optical density analyser. Results
      showed that during disinfection tests, efficacy could be over-estimated due to
      poor, or no, neutralization of the disinfectant after a specified time of
      exposure to the bacteria. The failure to distinguish adequately between
      bacteriostatic and bactericidal effects can lead to false results during
      disinfectant testing. Experiments also showed that dilution of the disinfectant,
      following exposure to the bacteria, was not always sufficient to stop the
      activity of the disinfectant for chemicals with low dilution coefficients.
      CONCLUSIONS: The quench test proved to be very quick and easy to perform, with
      results being available within 18 h. Using the Bioscreen, the test is automated
      and determines whether dilution into a particular neutralizer is able to
      inactivate a disinfectant within 30 s. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      new approach allows the efficacy of quenching agents to be determined, prior to
      undertaking each disinfection study, and can help in the development of more
      suitable quenching solutions. The test has also been used to find suitable
      neutralizers for mixtures of disinfectants which might be used during studies on
      synergistic biocide combinations.

PMID- 11966922
TI  - Microbial spoilage and formation of biogenic amines in fresh and thawed modified
      atmosphere-packed salmon (Salmo salar) at 2 degrees C.
AB  - AIMS: To evaluate the microbial spoilage, formation of biogenic amines and shelf
      life of chilled fresh and frozen/thawed salmon packed in a modified atmosphere
      and stored at 2 degrees C. METHODS AND RESULTS: The dominating microflora,
      formation of biogenic amines and shelf life were studied in two series of storage
      trials with naturally contaminated fresh and thawed modified atmosphere-packed
      (MAP) salmon at 2 degrees C. Photobacterium phosphoreum dominated the spoilage
      microflora of fresh MAP salmon at more than 10(6) cfu g(-1) and the activity of
      this specific spoilage organism (SSO) limited the shelf life of the product to ca
      14 and 21 d in the two experiments. Despite the high levels of P. phosphoreum,
      less than 20 mg kg(-1) histamine was observed in fresh MAP salmon prior to
      sensory spoilage. Freezing eliminated P. phosphoreum and extended the shelf life
      of MAP salmon at 2 degrees C by 1-2 weeks. Carnobacterium piscicola dominated the
      spoilage microflora of thawed MAP salmon and probably produced the ca 40 mg kg(
      1) tyramine detected in this product at the end of its shelf life. CONCLUSIONS:
      Photobacterium phosphoreum dominated the spoilage microflora of fresh MAP salmon
      but produced only small amounts of biogenic amines in this product. The
      elimination of P. phosphoreum by freezing allowed this bacteria to be identified
      as the SSO in fresh MAP salmon. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      identification of P. phosphoreum as the SSO in fresh MAP salmon facilitates the
      development of methods to determine and predict the shelf life of this product,
      as previously shown with fresh MAP cod.

PMID- 11966923
TI  - Relative effectiveness of powered and manual toothbrushes in elderly patients
      with implant-supported mandibular overdentures.
AB  - AIM: The aim of this study was to compare the clinical effectiveness of a powered
      toothbrush (Braun Oral-B Plaque Remover 3-D) and a manual soft toothbrush (Oral-B
      Squish-grip brush) for the control of supragingival plaque and soft tissue
      inflammation around implants supporting mandibular overdentures. MATERIAL AND
      METHODS: The study sample involved 40 edentulous subjects, aged 55-80 years,
      having 2 unsplinted mandibular implants supporting a complete removable
      overdenture opposed by a maxillary complete denture. In this single-blinded,
      randomised, cross-over clinical trial, two 6-week experimental phases were
      separated by a 2-week wash-out period. 2 weeks prior to each experimental phase
      (pre-entry visits), implant abutments were polished to remove all plaque and a
      standardised instruction in the use of the toothbrush was given. Modified plaque
      and bleeding indices were recorded at the start and end of each experimental
      period. Mean index scores at each phase were analysed using paired t-test, and
      the mean number of sites showing a change in plaque or mucositis were compared
      using the Mann-Whitney U-test. Combined data from 2 different implant systems
      were considered after controlling for implant type. RESULTS: Only minor changes
      in plaque and bleeding scores were observed following the two test periods. There
      were no statistically significant differences between the manual and powered
      toothbrushes. CONCLUSION: Manual and powered brushes were found to be of
      comparable efficacy with regard to improvement in peri-implant bleeding and
      plaque indices.

PMID- 11966925
TI  - Longitudinal association between plaque and gingival bleeding in smokers and non
      smokers.
AB  - BACKGROUND/AIMS: Whereas accumulation of dentogingival plaque inevitably leads to
      inflammatory reactions in the adjacent gingival tissue, there is limited
      information with regard to factors influencing naturally occurring fluctuation
      between gingival health and disease. The major aims of the present study were to
      investigate site-specific associations between plaque and gingivitis as well as
      transition dynamics of naturally occurring gingivitis in smoking and non-smoking
      young adults. METHODS: 65 systemically healthy young adults, 19 to 30 years old,
      participated. 33 volunteers smoked at least 20 cigarettes per day, whereas 32
      subjects were non-smokers. Clinical periodontal conditions were assessed four
      times within a time period of 6 months. An ecological approach in data analysis
      as well as site-specific analyses considering the correlated structure of data
      were performed. RESULTS: At the outset and after 6 months, smokers had
      significantly more supragingival plaque than non-smokers. At the final
      examination, bleeding upon probing as well as calculus were more prevalent in
      smokers. A site-by-site analysis revealed that smokers tended to have a weaker
      association between supragingival plaque and bleeding on probing than non-smokers
      (median Mantel-Haenszel's common odds ratio 1.91 vs. 2.89, p=0.07). Multiple
      logistic regression analyses adjusted for periodontal probing depth, plaque and
      calculus identified smoking status to significantly increase the risk for the
      first transition of non-bleeding to bleeding upon probing by 86% (p<0.01). In
      contrast, recovery of bleeding sites was positively influenced by female gender,
      but not smoking. CONCLUSIONS: In multivariate analyses adjusted for probing
      depth, plaque and calculus, smokers appeared to be at higher risk for the
      transition from non-bleeding to bleeding on probing. Weaker associations between
      plaque and naturally occurring gingivitis in smokers may have important
      consequences for preventive strategies for gingivitis.

PMID- 11966924
TI  - The presence of local and circulating autoreactive B cells in patients with
      advanced periodontitis.
AB  - AIM: The aim of the present investigation was to study the local (gingival) and
      systemic occurrence of autoreactive B cells (CD5+CD19 positive) in subjects with
      a high or low susceptibility to periodontitis. MATERIAL AND METHODS: 2 groups of
      subjects (Group A and B) susceptible to periodontitis were included. Group A
      consisted of 22 adult patients (7 females and 15 males, aged 24-66 years) with
      advanced and generalized chronic periodontitis and group B comprised 7 children
      (4 girls and 3 boys aged 9-13 years) with localized aggressive periodontitis. 26
      periodontally healthy subjects, Group C (aged 23-80 years, mean 49.6+/-16.3),
      were also recruited. Assessment of clinical and radiographical characteristics of
      periodontal disease was performed. Gingival biopsies and peripheral blood samples
      were obtained and prepared for immunohistochemical analysis. Blood samples only
      were obtained from the periodontally healthy subjects (group C). RESULTS: The
      proportion of autoreactive B cells (CD5+CD19 positive) of peripheral blood
      lymphocytes was about 6 times higher in group A and 4 times higher in group B
      than in the samples from the control subjects (group C). About 40-50% of the B
      cells in the peripheral blood of the periodontitis susceptible individuals
      expressed markers for autoreactive features while less than 15% of the
      circulating B cells in the subjects of group C exhibited such markers. The
      periodontitis lesion in the adult periodontitis patients contained a substantial
      number of B cells out of which about 30% demonstrated autoreactive features.
      CONCLUSION: It is suggested that both circulating and local B cells in
      periodontitis susceptible individuals have a higher propensity to autoreactive
      properties than B cells of patients with a low susceptibility to periodontitis.

PMID- 11966926
TI  - Comparative evaluation of adjunctive oral irrigation in diabetics.
AB  - AIM: The purpose of this study was to assess the response of diabetics to scaling
      and root planing treatment and subgingival oral irrigation as adjunctive therapy.
      METHOD: A total of 52 type 1 and 2 diabetics (mean age 51.3+/-14) with adult
      periodontitis were randomized to two groups. Treatment included ultrasonic
      scaling and scaling and root planing in both groups (control and test) plus
      subgingival water irrigation 2x daily for the test group. Assessments were made
      prior to and at 6 and 12 weeks after treatment. Parameters measured were modified
      gingival index (MGI), probing pocket depth (PPD), plaque index (PI), clinical
      attachment level (CAL), and bleeding on probing (BOP). Systemic measurement of
      Reactive Oxygen Species (ROS) generation, cytokines (TNF-alpha, IL-1beta, IL-10,
      and PGE2), and glycated hemoglobin (HbA1C). RESULTS: After treatment, analysis of
      data showed that both groups had clinical and systemic improvement. The test
      group had a statistically significant reduction for MGI, PI, and BOP compared to
      controls (p<0.03) at 12 weeks and for ROS generation at 12 weeks (p<0.012).
      Unlike controls, systemic analysis of cytokines showed a statistically
      significant reduction from baseline for IL-1beta at 6 weeks and PGE2 at 6 and 12
      weeks (p<0.05) within test group. CONCLUSION: These results suggest that scaling
      and root planing and adjunctive therapy may be of value in establishing a healthy
      periodontium in diabetics.

PMID- 11966927
TI  - Evaluation of the effectiveness of a pre-brushing rinse in plaque removal: a meta
      analysis.
AB  - OBJECTIVES: A meta-analysis technique was used to pool data from studies to
      assess the effectiveness of the pre-brushing rinse PLAX on existing plaque and
      gingivitis. METHODS: Studies were identified using MEDLINE and other sources, and
      grouped according to whether PLAX was used in short- or long-term treatment. The
      quality of trials was assessed by 2 independent readers. The DerSimonian and
      Laird random effects model was used. Meta-analyses were performed according to
      duration and type of PLAX treatment. In "1-day" studies, the effect of PLAX after
      rinsing and after rinsing and brushing was evaluated, whereas in longitudinal
      studies, this was done at several follow-up times. RESULTS: A total of 19 studies
      were included and mean quality scores ranged from 0.13 to 0.60, for the study
      protocol from 0.18 to 0.70 and for data analysis and presentation from 0.05 to
      0.53. In "1-day" studies, PLAX significantly reduced plaque after rinsing
      (difference=0.143; 95% CI=0.02-0.27;p=0.022), whereas no significant reduction
      was observed in post-brushing measures. In "longitudinal" studies, plaque was
      significantly reduced at 1-2 (difference=0.168; 95% CI=0.09-0.24; p<0.0001), 3-4
      (difference=0.179; 95% CI=0.01-0.35; p=0.043), 12 (difference=0.288; 95% CI=0.21
      0.37; p<0.0001) and 24 (difference=0.377; 95% CI=0.19-0.57; p=0.0001) weeks. The
      meta-analysis that evaluated gingivitis showed a significant reduction in
      inflammation with PLAX treatment at 12 (difference=0.209; 95% CI=0.17-0.25;
      p<0.0001) and 24 (difference=0.257; 95% CI=0.22-0.29; p<0.0001) weeks follow-up.
      CONCLUSIONS: Although PLAX use appears to offer some benefit in plaque and
      gingivitis reduction, the clinical magnitude of the difference and the benefit on
      oral health are likely to be small.

PMID- 11966928
TI  - Comparative professional plaque removal study using 8 branded toothbrushes.
AB  - BACKGROUND AND AIM: Considerable interest has been shown in the plaque removal
      properties of modern toothbrush designs. The primary aim of the study was to
      compare the plaque removal properties of 8 relatively recent designs of manual
      toothbrush using a professional tooth brusher and within a commonly used time
      frame. A secondary aim was established to utilise the data to observationally
      appraise plaque accumulation together with the patterns of removal as a
      consequence of using the timed professional tooth brusher. METHOD: The method was
      an 8-period, single-examiner, randomized, blind cross-over study involving 24
      healthy volunteers, balanced for residual effects. Subjects accumulated plaque
      over a 4 day no oral hygiene period. On day 4, the accumulated plaque was scored
      by plaque index at the mesial, mid and distal sites of each of the buccal and
      lingual surfaces of the assessed teeth. Subjects were then removed from the
      assessment area where they received a professional brushing timed to last 48 s.
      Brushing was completed according to pre-study training without toothpaste and was
      followed by a re-scoring of the remaining plaque. A washout period of 3 days was
      then allowed prior to the next period during which normal oral hygiene was
      resumed. RESULTS: Similar quantities of plaque accumulated in each arch, although
      the difference between the buccal and lingual surfaces was of the order of 30%.
      The professional toothbrusher removed approximately 40% of the accumulated plaque
      in the 48 s allocated. The buccal surfaces were most effectively cleaned
      (approximately 45%) compared with the lingual (approximately 25%), with the
      plaque removal in the mesial and mid sections approaching 40% and 60%
      respectively. The difference in performance between the test brushes corresponded
      to 5% of the residual plaque values with none being significantly more efficient
      overall. Pair wise site comparisons did produce differences of the order of 10%
      (p=0.004) at the mesio-buccal, and 8% (p=0.030) at the mid-buccal sites
      respectively in favour of 2 brushes compared to one other brush. CONCLUSIONS:
      These data derived from a standardized brushing method support the contention of
      many researchers that there is no one superior design of manual toothbrush. The
      minor and few site differences in favour of some brushes are unlikely to be of
      clinical significance to gingival health. This leaves uncontested the conclusion
      that the user is by far the most significant variable. Perhaps methods such as
      used in the present study could be more gainly employed to set a minimum standard
      of toothbrush efficacy.

PMID- 11966929
TI  - Enamel matrix proteins in the regenerative therapy of deep intrabony defects.
AB  - AIM: This prospective multicentre randomized controlled clinical trial was
      designed to compare the clinical outcomes of papilla preservation flap surgery
      with or without the application of enamel matrix proteins (EMD). MATERIAL AND
      METHODS: 172 patients with advanced chronic periodontitis were recruited in 12
      centers in 7 countries. All patients had at least one intrabony defect of > or
      =3mm. Heavy smokers (> or =20 cigarettes/day) were excluded. The surgical
      procedures included access for root instrumentation using either the simplified
      or the modified papilla preservation flap in order to obtain optimal tissue
      adaptation and primary closure. After debridement, roots were conditioned for 2
      min with a gel containing 24% EDTA. EMD was applied in the test subjects, and
      omitted in the controls. Postsurgically, a strict plaque control protocol was
      followed. At baseline and 1 year following the interventions, clinical attachment
      levels (CAL), pocket probing depths (PPD), recession (REC), full-mouth plaque
      scores and full-mouth bleeding scores were assessed. A total of 166 patients were
      available for the 1-year follow-up. RESULTS: At baseline, 86 test and 86 control
      patients presented with similar subject and defect characteristics. On average,
      the test defects gained 3.1+/-1.5 mm of CAL, while the control defects yielded a
      significantly lower CAL gain of 2.5+/-1.5 mm. Pocket reduction was also
      significantly higher in the test group (3.9+/-1.7 mm) when compared to the
      controls (3.3+/-1.7 mm). A multivariate analysis indicated that the treatment,
      the clinical centers, cigarette smoking, baseline PPD, and defect corticalisation
      significantly influenced CAL gains. A frequency distribution analysis of the
      studied outcomes indicated that EMD increased the predictability of clinically
      significant results (CAL gains > or =4 mm) and decreased the probability of
      obtaining negligible or no gains in CAL (CAL gains <2 mm). CONCLUSIONS: The
      results of this trial indicated that regenerative periodontal surgery with EMD
      offers an additional benefit in terms of CAL gains, PPD reductions and
      predictability of outcomes with respect to papilla preservation flaps alone.

PMID- 11966930
TI  - Psychosocial stress, lifestyle and periodontal health.
AB  - BACKGROUND, AIMS: The hypothesis that psychosocial stress and lifestyle are
      related to periodontal status was tested. MATERIAL AND METHODS: The study was
      performed in 1997-98 in 10 areas in Lithuania (response rate 53%). Information
      comprised recordings of oral hygiene, calculated levels of remaining periodontal
      support and information about psychosocial and lifestyle factors. A hypothetical
      structure was tested in 2 age and gender subgroups by means of a structural
      equation model both for an overall fit and for the fit of individual parameters
      within the model. RESULTS: The hypothesised structure presented high confirmatory
      fit index values (CFI) in all subgroup models, i.e., CFI >0.94. However the
      probability value of 0.01 found in the older males model presented an unlikely
      event. When individual parameters within the models were tested, different
      misspecifications were found. Therefore the hypothesised structure needed to be
      revised and tested repeatedly. All revised models presented high CFI and
      probability values (p>0.35). The testing of individual parameters did not reveal
      any significantly misspecified parameters. CONCLUSIONS: The path between
      lifestyle and levels of remaining periodontal support was empirically supported
      in the present study. Although the pathway between psychosocial stress and
      remaining periodontal support was not empirically supported, there is reason to
      believe that such link is likely.

PMID- 11966931
TI  - 5 polymorphisms in the transforming growth factor-beta 1 gene (TGF-beta 1) in
      adult periodontitis.
AB  - OBJECTIVES: Transforming growth factor-beta (TGF-beta) represents a family of
      polypeptide growth factors, involved in inflammation and regulation of immune
      responses. The purpose of this study was to determine whether polymorphisms in
      the TGF-beta 1 gene may confer susceptibility to adult periodontitis. MATERIAL
      AND METHODS: We studied 90 patients with adult periodontitis together with 108
      unrelated subjects. 3 polymorphisms located in the 5'region at positions -988
      (C/A), -800 (G/A) and -509 (C/T) and 2 polymorphisms located at codons 10 (L10P)
      and 25 (R25P) of exon 1 were investigated by PCR methods. RESULTS: There was no
      statistically-significant difference in genotype or allele frequency
      distributions between patients and reference group for the -800G/A, -509C/T, L10P
      and R25P polymorphisms (p>0.05 in all cases). The -988 A polymorphism was present
      neither in our patients nor in unrelated subjects. Upon stratification for
      smoking status no significant differences were found in the TGF-beta 1 genotype
      or allele frequencies either between adult periodontitis smokers compared to
      control smokers, or between periodontitis non-smokers and control non-smokers.
      CONCLUSION: These data indicate that the mentioned polymorphisms of the TGF-beta
      1 gene do not influence susceptibility to adult periodontitis. There was no
      association between any polymorphisms in the TGF-beta 1 gene, severity of
      periodontitis and the smoking status in our study.

PMID- 11966932
TI  - Adjunctive effects to non-surgical periodontal therapy of systemic metronidazole
      and amoxycillin alone and combined. A placebo controlled study.
AB  - BACKGROUND AND AIM: Several studies have reported adjunctive benefits to scaling
      and root planing (SRP) of systemic amoxycillin and metronidazole in the treatment
      of periodontal diseases. To date no comparisons have been made of these
      antimicrobials alone or in combination. The aim of this study was to compare the
      adjunctive benefits to SRP of amoxycillin and metronidazole alone and combined.
      METHODS: 66 subjects <46 years of age with advanced chronic periodontal disease
      participated in this randomised, double blind, 4 parallel treatment group
      designed study. All subjects received quadrant SRP and then were prescribed
      amoxycillin capsules (250 mg) and metronidazole tablets (200 mg) (AM) or lactate
      capsules and metronidazole (PM) or amoxycillin and calcium lactate tablets (AP)
      or lactate and calcium lactate (PP). All medication was 3 of each per day for 7
      days. Subgingival plaque samples were obtained and probing depth (PD), loss of
      attachment (LOA), bleeding on probing (BOP), suppuration (SUPP) and plaque (DEP)
      were recorded pre-treatment, 1, 3 and 6 months post-treatment. RESULTS: Final
      group sizes were: AM=15, PM=16, AP=16 and PP=15. PD improved in all groups.
      Treatment effects were highly significantly different and always greatest in the
      AM and least in the PP groups. Benefits of PM and AP over PP were also noted. LOA
      improved in all groups and showed the same highly significant treatment
      differences, again favouring AM. BOP improved in all groups, particularly in AM
      compared to the other groups. SUPP improved in all groups and was virtually
      eradicated in AM with differences among treatments highly significant. DEP
      changed little in any group and there were no significant differences among
      groups. Microbiological data showed significant differences in favour of AM
      compared to PP and PM for total aerobes and anaerobes at 1 month. P. intermedia
      counts were always lower in active groups compared to PP and reached significance
      for AM and AP at 1 month and AM and PM at 3 months. CONCLUSION: The significant
      differences among treatment groups and the overall trend in the data, in line
      with other studies, support the considerable adjunctive benefits to SRP of
      amoxycillin and metronidazole combined in the treatment of advanced chronic
      periodontal disease.

PMID- 11966933
TI  - Cervical tooth wear and sensitivity: erosion, softening and rehardening of
      dentine; effects of pH, time and ultrasonication.
AB  - BACKGROUND: Cervical dentine wear is commonly observed and may be associated with
      dentine hypersensitivity. Erosion is thought to play a part in both conditions
      but compared to enamel has been little studied in dentine. AIM: The aims of these
      studies in vitro were to: (i) determine the effects of citric acid on dentine at
      different pH values and over time; (ii) measure the depth of dentine
      demineralisation or softening using ultrasonication; (iii) determine whether
      softened dentine can be remineralised or rehardened using artificial saliva.
      METHODS: Groups of flat dentine specimens prepared from unerupted human third
      molar teeth were: (a) exposed to citric acid at pH 3.2 for periods up to 4 h with
      mineral water as control; (b) exposed to citric acid at pH 2.54, 3.2, 4.5, 5.5
      and 6.0 for 2 h and then subjected to ultrasonication stepwise up to 480 s; (c)
      exposed to citric acid at pH 2.54, 3.2, and 4.5, placed into artificial saliva
      for 24 h and then subjected to ultrasonication as in (b). Loss of dentine was
      measured by profilometry, after, each phase of erosion, ultrasonication and
      immersion in artificial saliva. RESULTS: Depth of erosion significantly increased
      non-linearly with time and significantly decreased with increasing pH.
      Ultrasonication had minimal albeit significant effects on control specimens.
      Removal of softened dentine increased with ultrasonication time. Depth of
      softening significantly increased with increasing erosion time to 2 h, plateauing
      at 2 microm. Depth of softening increased to 2 microm from pH 2.54 to pH 3.2 and
      decreased at higher pH values thereafter. 24 h in artificial saliva provided no
      protection to the soften zone against ultrasonicaion. Citric acid at all pH
      values and exposure times removed the dentine smear layer to expose tubules.
      Ultrasonication did not remove the smear layer on control specimens but removed
      all deposits formed after exposure to artificial saliva. CONCLUSION: It is
      concluded that dentine is susceptible to erosion even at relatively high pH, the
      tubule system is readily exposed and dentine, unlike enamel, shows little
      propensity to remineralise.

PMID- 11966934
TI  - Effect of an amine-fluoride-triclosan mouthrinse on plaque regrowth and biofilm
      vitality.
AB  - BACKGROUND: The purpose of this double-blind, prospective, latin-square crossover
      randomised study was to examine the efficacy of a mouthrinse solution containing
      a combination of triclosan, amine fluoride and sodium fluoride on supragingival
      plaque regrowth compared to a placebo and a chlorhexidine solution. METHODS: 12
      volunteers refrained after professional oral prophylaxis from all mechanical
      hygiene measures for the following 96 h and rinsed instead cross-over in a
      randomised order with either chlorhexidine digluconate (0.2%, positive control),
      a verum solution (0.5% amine fluoride, 0.028% sodium fluoride, 0.03% triclosan)
      or a placebo solution. The plaque index was assessed after 24 and 96 h (PI 1, PI
      2) and the plaque area (PA) photographed and calculated after 96 h of undisturbed
      plaque regrowth. Moreover plaque samples were taken after 24 and 96 h and
      examined with the vital fluorescence technique to assess the vitality of the
      biofilm microbiota (VF 1, VF 2). RESULTS: The amine-fluoride-triclosan solution
      reduced the clinical parameters (PI and PA) as well as the vitality of the plaque
      flora (VF) significantly when compared to the placebo solution. The verum reached
      a 36.5% (p<0.05) and a 39.8% reduction (p<0.0001) in PI 1 and PI 2, respectively,
      concomittant with a reduction of 23.8% and 32.2% (p<0.001) in VF 1 and VF 2 and
      of 46.9% (p<0.0001) in PA at day 4. This was less than the reductions found with
      the positive control, i.e., the 0.2% chlorhexidine solution (54.2% and 71.1%
      reduction in PI 1 and PI 2, 40.0% and 53.4% in VF 1 and VF 2 and 71.5% in PA).
      However, significant differences between both active solutions were only
      established for PI 2 and PA. CONCLUSION: During 4-day plaque regrowth the amine
      fluoride-triclosan product displayed a significant antibacterial and plaque
      reducing action in comparison to the control.

PMID- 11966935
TI  - Local application of n-3 or n-6 polyunsaturated fatty acids in the treatment of
      human experimental gingivitis.
AB  - BACKGROUND: Polyunsaturated fatty acids have the potential to attenuate
      inflammation by the synthesis of mediators of the 15-lipoxygenase pathways, which
      show opposite effects to the pro-inflammatory arachidonic acid metabolites such
      as leukotriene B4 (LTB4). AIMS: The aim of this clinical study was to evaluate
      the effects of topical application of n-6 or n-6 polyunsaturated fatty acids in
      patients with experimental gingivitis. METHODS: In each subject, similar teeth
      served as experimental and control over a 21-day non-hygiene phase and a 9-day
      resolving phase. Efficacy assessment was based on the bleeding on probing
      frequency (BOP) and the gingivocrevicular fluid volume (GCF). GCF was determined
      by inserting a filter paper strip for 30 s and measurements were performed on a
      Periotron 8000. The LTB4 concentration was analyzed by reversed-phase high
      pressure liquid chromatography. RESULTS: After 21 days of plaque growth, the BOP,
      GCF and LTB4 levels were significantly increased in all groups, with no
      differences between the control and experimental side. Rinsing of an area with
      established gingivitis for a 9-day period significantly reduced the GCF in the n
      6 group (71.9 (18.7) versus 47.4 (11.4) Periotron Units, median (inter quartile
      range)). CONCLUSION: The topical application of n-6 or n-6 fatty acids failed to
      inhibit the development of experimental gingivitis. Rinsing with n-6 fatty acids
      could reduce the level of GCF in established experimental gingivitis.

PMID- 11966936
TI  - Treatment of Papillon-Lefevre syndrome periodontitis.
AB  - BACKGROUND, AIMS: Conventional mechanical treatment of Papillon-Lefevre syndrome
      periodontitis has a poor prognosis. This report describes an effective
      antimicrobial treatment of rapidly progressing periodontitis in an 11-year old
      girl having Papillon-Lefevre syndrome. METHOD: Clinical examination included
      conventional periodontal measurements and radiographic analysis. Occurrence of
      major suspected periodontopathic bacteria was determined by selective and non
      selective culture and by polymerase chain reaction (PCR) identification. Presence
      of cytomegalovirus and Epstein-Barr type 1 virus was determined by a nested-PCR
      detection method. Therapy included scaling and root planing, oral hygiene
      instruction, and systemic amoxicillin-metronidazole therapy (250 mg of each/3
      times daily/10 days) which, based on follow-up microbiological testing, was
      repeated after 4 months. Supportive periodontal therapy took place at 2 visits
      during a 16-month period. RESULTS: At baseline, 10 of 22 available teeth
      demonstrated severe periodontal breakdown. At 16 months, probing and radiographic
      measurements revealed no teeth with additional attachment loss, and several teeth
      exhibited significant reduction in gingivitis and pocket depth, increase in
      radiographic alveolar bone height and clinical attachment level, and radiographic
      evidence of crestal lamina dura. Baseline subgingival microbiota included
      Actinobacillus actinomycetemcomitans (3.4% of total isolates), Prevotella
      nigrescens (16.4%), Fusobacteriumnucleatum (14.3%) and Peptostreptococcus micros
      (10.6%), as well as cytomegalovirus and Epstein-Barr type 1 virus. At termination
      of the study, culture and PCR examinations showed absence of A.
      actinomycetemcomitans, P. micros and herpesviruses, and P. nigrescens and
      F.nucleatum each comprised less than 0.1 % of subgingival isolates. CONCLUSION:
      This study suggests that controlling the periodontopathic microbiota by
      appropriate antibiotic and conventional periodontal therapy can arrest Papillon
      Lefevre syndrome periodontitis.

PMID- 11966938
TI  - Clinical relevance of hepatitis B viral genotypes: a case of deja vu?

PMID- 11966939
TI  - New approaches to immunosuppression in liver transplantation.
AB  - With the continued improvements in outcome following liver transplantation, the
      drawbacks associated with conventional immunosuppression regimens become
      increasingly apparent. Although up to 70% of patients develop a histological
      infiltrate of the graft (acute rejection), many of these will resolve
      spontaneously, and chronic rejection is rare. If a robust form of allograft
      acceptance or tolerance can be established, then immunosuppression can be
      withdrawn along with all the accompanying risks. The liver is already known to be
      associated with downregulated immune responses; the mechanism for this is
      unclear, but may be related to a number of mechanisms known to be involved in
      peripheral tolerance. There are many strategies being studied for achieving
      allograft tolerance, including the use of modern immunosuppressants, antibodies
      that target key molecules in the immune response, and recruitment of leukocytes
      to allografts. In the interim, it is necessary to look for safe protocols that
      allow trials of tolerance strategies without putting patients at increased risk.

PMID- 11966940
TI  - Evaluation of a new formulation CLOtest.
AB  - BACKGROUND AND AIMS: The CLOtest and other rapid urease detection kits are widely
      used in the endoscopic diagnosis of Helicobacter pylori. A new formulation
      CLOtest has been developed with the goal of obtaining a positive result more
      rapidly. The aims of this study were to validate the sensitivity and specificity
      of the new test and compare the time taken for a positive result to be visible in
      both the new and standard CLOtest. METHODS: Patients presenting for endoscopy at
      three Western Australian hospitals were prospectively enrolled. Gastric mucosal
      biopsies were obtained for the standard and new CLOtest and for histology.
      Grading of color change was conducted by staff blinded to the type of CLOtest
      used and conducted according to a standardized color chart. Helicobacter pylori
      status was defined by the combination of a positive standard CLOtest and
      histology, against which the new CLOtest was compared. Results were obtained at
      1, 3 and 24 h, and at one center, at 10 min intervals for the first hour.
      RESULTS: Three hundred and thirty-five patients were enrolled. Eighty-eight
      Helicobacter pylori-positive individuals were identified. At 24 h, the new test
      correctly identified all 88, with one false-positive result (sensitivity 100%,
      specificity 99.6%). At 1 h, sensitivity was 93% with a number of early false
      positive results reducing specificity to 96%. Compared to the current CLOtest,
      the new formulation became positive faster at 20 min (P = 0.001, n = 51), but was
      similar at 1 h (P = 0.06, n = 88) and equivalent at 3 h. CONCLUSIONS: The new
      formulation CLOtest is sensitive and specific, with a trend to give early
      positive results more quickly, although accuracy at 3 and 24 h is the same.

PMID- 11966941
TI  - Higher seroprevalence of Helicobacter pylori infection in Korean adolescent
      athletes compared to age- and sex-matched non-athletes.
AB  - BACKGROUND: Poor living conditions, such as overcrowding and bed-sharing, are
      reported to be significant risk factors for Helicobacter pylori infection
      throughout childhood. We investigated the prevalence of H. pylori infection in
      Korean athletes who are obliged to live together in training camps for more than
      6 months in a year. METHODS: Blood sampling and surveying through questionnaire
      were performed on 440 students from a regular high school (228 boys and 212
      girls) and 220 athletes (148 boys and 72 girls) of a physical education high
      school. We measured serum immunoglobulin G antibody (IgG Ab) to H. pylori in
      order to compare the prevalence of H. pylori infection between normal adolescents
      and athletes. In addition, we conducted a nutritional analysis and questionnaire
      survey for socioeconomic status in order to compare other risk factors that might
      influence H. pylori infection between groups. RESULTS: The prevalence of H.
      pylori infection in athletes (43.2%) was higher than that in the controls
      (22.7%). No significant differences in the nutritional factors or socioeconomic
      status, such as Hollingshead index, type of house, number of siblings, and
      crowding index, were found between the groups. Multivariate analysis showed that
      crowding and the difference in school type were the significant predictors of H.
      pylori seropositivity after controlling for dietary and socioeconomic factors.
      CONCLUSION: The seroprevalence of H. pylori infection was higher in adolescent
      athletes than in age- and sex-matched regular students. Further prospective study
      is needed to confirm the observation.

PMID- 11966942
TI  - Early studies on the safety and efficacy of thalidomide for symptomatic
      inflammatory bowel disease.
AB  - BACKGROUND AND AIM: Thalidomide is clinically effective in the treatment of graft
      versus host disease in bone marrow transplantation and aphthous ulceration in HIV
      infection. It appears to exert a selective effect on tumor necrosis factor-alpha
      (TNF-alpha) production. Tumor necrosis factor-alpha is implicated in the
      pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to
      assess the efficacy and safety of thalidomide in symptomatic IBD. METHODS: Eleven
      patients (nine males, mean age 33 years, range 20-77 years) with chronic
      inflammatory bowel disease (six Crohn's disease (CD), four ulcerative colitis
      (UC), one indeterminate colitis (IC)) who were symptomatic despite standard
      medical therapy were administered a daily dose of thalidomide for 12 weeks in an
      open-labeled protocol. Their response was assessed by using clinical,
      colonoscopic, histological, and immunological methods. RESULTS: Two patients
      withdrew at 3 weeks because of mood disturbances. Of the remaining nine patients,
      eight (five CD, two UC and one IC) had a marked clinical response, while one
      patient with CD had no response. The mean stool frequency decreased from 4.3 to
      2.3 per day (P = 0.0012), and the stool consistency increased from 2.1 to 1.2 (P
      = 0.02). The mean Crohn's Disease Activity Index decreased from 117 to 48 (P =
      0.0008). Endoscopic inflammatory and histological grade, C-reactive protein and
      erythrocyte sedimentation rate (ESR) all decreased significantly (P = 0.011, P =
      0.03, P = 0.023 and P = 0.044, respectively). However, the serum TNF-alpha levels
      did not change. Side-effects included mild sedation, xerostomia and skin dryness
      in all, constipation in three, and minor abnormalities in nerve conduction in one
      patient. CONCLUSION: These data strongly suggest that thalidomide is an effective
      short-term treatment for symptomatic IBD.

PMID- 11966943
TI  - Plasma and urine levels of urinary trypsin inhibitor in patients with acute and
      fulminant hepatitis.
AB  - BACKGROUND AND AIM: Urinary trypsin inhibitor (UTI) is synthesized by hepatocytes
      and excreted into urine. Plasma and urine UTI levels have been measured to
      evaluate whether these levels may be useful markers in various pathological
      conditions. However, there has been no study on plasma and urine UTI levels in
      patients with acute liver diseases. The aim of the present study was to evaluate
      plasma and urine UTI levels and their relationship with the severity of hepatic
      damage in patients with acute liver diseases. METHODS: Plasma and urine UTI
      levels were measured by newly developed enzyme-linked immunosorbent assay in 15
      patients with acute hepatitis (AH), 12 patients with acute severe hepatitis (ASH)
      and 10 patients with fulminant hepatitis (FH), as assessed on admission. The
      serial changes in plasma and urine UTI were also observed in some patients with
      AH and ASH. RESULTS: Plasma UTI levels (U/mL, median [25-75th percentile]) were:
      11.0, (9.5-16.1) in patients with AH; 7.8 (5.6-11.5) in those with ASH; 6.5 (4.0
      9.5) in patients with FH; and 9.7 (7.3-11.0) in normal controls. Plasma UTI
      levels in patients with FH were significantly lower than in those with AH. Plasma
      UTI levels showed significant positive correlations with the levels of
      prothrombin time (PT), hepaplastin test, antithrombin III, alpha2-plasmin
      inhibitor, plasminogen (Plg) and fibrinogen. After the recovery of liver
      dysfunction, increased plasma UTI levels in patients with AH were decreased,
      whereas previously decreased plasma UTI levels in patients with ASH were
      increased. Urine UTI levels were significantly increased in patients with AH
      compared with those of normal controls. In patients with ASH and FH, urine UTI
      levels were increased but not significantly. Urine UTI levels significantly
      positively correlated with PT and Plg. After the recovery of liver dysfunction,
      previously increased urine UTI levels in patients with AH were decreased. The
      correlation between plasma UTI and urine UTI levels was not significant.
      CONCLUSIONS: The findings of the present study suggested that the levels of
      plasma and urine UTI changed in patients with AH and were closely related to the
      abnormalities of coagulo-fibrinolysis, including PT. Further studies are needed
      to clarify whether these levels may be useful markers to predict the prognosis of
      acute hepatitis.

PMID- 11966944
TI  - Wild-type and 'a' epitope variants in chronic hepatitis B virus carriers positive
      for hepatitis B surface antigen and antibody.
AB  - AIMS: This study aims to examine the genomic variants of the 'a' epitope in
      chronic hepatitis B virus (HBV) carriers positive for both hepatitis B surface
      antigen (HBsAg) and antibody to HBsAg (anti-HBs). METHODS: Eighteen HBV carriers
      were studied. Hepatitis B virus (HBV) DNA was extracted and the 'a' epitope
      region was amplified and sequenced. RESULTS: Eighteen Chinese asymptomatic HBV
      carriers were studied. There were 13 patients who were positive for both HBsAg
      and anti-HBs. Of these, one patient had only wild-type HBV, three had a viral
      mixture, and five had only 'a' epitope variant HBV. Of the three patients with a
      viral mixture, all had variants in the less conserved region (123-137). Of the
      five patients with pure HBsAg mutants, three had variants in the less conserved
      region while two had variants in the highly conserved region. In this study with
      a limited number of patients, the serum alanine aminotransferase (ALT) levels
      were higher in patients with wild-type HBV, compared with those with either 'a'
      epitope variants or a viral mixture consisting of wild type and variants.
      CONCLUSION: Eight of the nine (89%) patients positive for both HBsAg and anti-HBs
      harbored an 'a' epitope variant. The lower ALT levels seen in patients who had
      either pure 'a' epitope variant or a mixture of wild type and mutants suggest
      that a closer monitoring of these 'a' epitope variants should be required, as
      patients carrying these infectious viral strains may remain asymptomatic.

PMID- 11966945
TI  - Introduction of lamivudine for the treatment of chronic hepatitis B: expected
      clinical and economic outcomes based on 4-year clinical trial data.
AB  - BACKGROUND: Chronic hepatitis B (CHB) is associated with a significant burden of
      illness and treatment involves substantial health-care costs. This study
      estimates clinical outcomes and cost-effectiveness of lamivudine compared with
      other treatment scenarios for CHB, from an Australian health-care provider
      perspective. METHODS: A two-step modeling approach depicted clinical progression
      of hepatitis B in hypothetical patient cohorts using three different treatment
      scenarios: scenario A, lamivudine and alpha-interferon (IFN-alpha) available;
      scenario B, IFN-alpha available only; and scenario C, no treatment available.
      Assumptions were based on clinical trials, published studies, a hepatologist's
      questionnaire and an expert panel follow up. One-year clinical outcomes and costs
      were estimated using a decision tree, while lifetime costs and outcomes were
      estimated using available clinical trial data for lamivudine (up to 4 years
      therapy duration) and a Markov model. RESULTS: The analysis considered only
      patients with pretreatment elevated alanine aminotransferase levels > or = 2 x
      upper limit of normal. In the short term, the introduction of lamivudine is
      expected to result in almost 3.5 times more CHB patients receiving therapy
      (lamivudine or IFN-alpha) compared to IFN-alpha only (67% compared to 20%,
      respectively). Hence, scenario A subsequently doubled the seroconversion rate.
      The incremental cost-effectiveness ratio was $3341 Australian per additional
      seroconversion. Also, non-seroconverted lamivudine patients are less likely to
      progress to cirrhosis than those receiving IFN-alpha/no treatment. One-year
      progression to cirrhosis was estimated at 5.1% with scenario A, compared to 12.2%
      and 12.7%, scenarios B and C, respectively. From the long-term analysis,
      lamivudine is expected to increase life expectancy by years and reduce the
      lifetime risk of compensated cirrhosis, decompensated cirrhosis and
      hepatocellular carcinoma by 6%, 12% and 12%, respectively. Additionally, the
      introduction of lamivudine decreases lifetime costs by $548, thus making it a
      cost-saving and life-extending strategy. In both short- and long-term models,
      worst case scenarios in sensitivity analyses still associate lamivudine with a
      favorable cost-effectiveness ratio. CONCLUSION: Introduction of lamivudine is
      expected to improve health outcomes in CHB patients, resulting in overall savings
      in health-care costs. In this model, compared with IFN-alpha only and no
      treatment, lamivudine allowed more CHB patients to be treated, increased the
      seroconversion rate, delayed disease progression and prolonged life expectancy.

PMID- 11966946
TI  - Profile, spectrum and significance of HBV genotypes in chronic liver disease
      patients in the Indian subcontinent.
AB  - BACKGROUND AND AIM: Certain hepatitis B virus (HBV) genotypes have been alleged
      to be associated with the development of cirrhosis and hepatocellular carcinoma
      (HCC), and the response to interferon therapy in Taiwanese patients. We undertook
      to study the prevalence and significance of HBV genotypes in the Indian
      subcontinent. METHODS: One hundred and thirty histopathologically proven chronic
      HBV-infected patients, including 52 incidentally detected asymptomatic hepatitis
      B surface antigen (HBsAg)-positive subjects (IDAHS) with chronic HBV infection
      (group I), 48 cirrhotics (group II) and 30 hepatocellular carcinoma (HCC; group
      III) patients were studied. Hepatitis B virus genotypes were determined by using
      restriction fragment length polymorphism, and direct sequencing of the s gene
      including the 'a' determinant region. RESULTS: Only genotypes A (46%) and D (48%)
      were found in the chronic HBV-infected patients. A mixed infection with genotypes
      A and D was seen in 6% of patients. Genotype A was found in 42, 48 and 50%, and
      genotype D in 48, 50 and 47% of group I, II and III patients, respectively (P =
      NS). The patients who had mixed genotypes were significantly younger (P < 0.05).
      In group I (IDAHS) patients infected with genotype D, none had a histological
      activity index (HAI) of < four. Genotype D was significantly more common in group
      I patients with HAI > 4 as compared to genotype A (53 vs 32%, P < 0.05).
      Similarly, genotype D was associated with more severe liver diseases (61 vs 30%,
      P < 0.05). Genotype D was more prevalent in HCC patients of < 40 years of age, as
      compared to IDAHS (63 vs 44%, P = 0.06). CONCLUSIONS: (i) Hepatitis B virus
      genotypes A and D are prevalent in chronic liver disease patients of Indian
      origin; and (ii) HBV genotype D is associated with more severe diseases and may
      predict the occurrence of HCC in young patients.

PMID- 11966947
TI  - Fatigue and psychological disorders in chronic hepatitis C.
AB  - BACKGROUND AND AIM: Most patients with chronic hepatitis C report that they
      suffer from fatigue. The aim of this study was to determine if the symptom of
      fatigue can be a guide to indicate disease activity in chronic hepatitis C, or if
      it is related to psychological factors. METHODS: 115 chronic hepatitis C patients
      attending a liver clinic at Wollongong Hospital, Wollongong, Australia, were
      asked to fill out a questionnaire on the functional impact of their fatigue, and
      a questionnaire on psychological parameters. These were correlated with a history
      of intravenous drug use, alcohol history, transaminase levels and liver biopsy
      findings. RESULTS: Fatigue weakly correlated with the level of fibrosis on the
      liver biopsy, but strongly correlated with all the psychological domains of
      depression, anxiety, somatization, interpersonal sensitivity and hostility.
      CONCLUSION: The level of fatigue strongly correlated with all the psychological
      domains, particularly depression, and not with our measures of disease activity.

PMID- 11966948
TI  - Polymorphism in alcohol-metabolizing enzymes, glutathione S-transferases and
      apolipoprotein E and susceptibility to alcohol-induced cirrhosis and chronic
      pancreatitis.
AB  - BACKGROUND AND AIM: Susceptibility to organ damage induced by alcohol may be due
      to inherited variation (polymorphism) in ethanol-metabolizing enzymes, or to
      polymorphisms affecting free radical or lipid metabolism mediated by enzymes such
      as glutathione S-transferases and apolipoprotein E. The aim was to compare the
      genotype frequencies of alcohol dehydrogenase-2 (ADH2), ADH3, aldehyde
      dehydrogenase-2 (ALDH2), cytochrome P450-2E1 (CYP2E1), glutathione S-transferase
      M1 (GSTM1), GSTT1, and apolipoprotein E in patients with alcoholic cirrhosis and
      alcoholic chronic pancreatitis to those in control groups. PATIENTS AND METHODS:
      The case-control study was restricted to Caucasian adults: 57 with alcoholic
      cirrhosis, 71 with alcoholic chronic pancreatitis, 57 alcoholics without apparent
      organ damage and 200 healthy blood donors. Genotypes were determined by
      restriction fragment length polymorphism after amplification of genomic DNA by
      polymerase chain reaction. RESULTS: The genotype ADH3*2/*2 was more frequent in
      patients with cirrhosis (40%) than blood donors (12%; OR 4.92, 95% CI 2.36-10.31)
      and patients with chronic pancreatitis (8%; OR 7.33, 95% CI 2.54-23.78) but was
      not significantly different from alcoholic controls (23%; OR 2.27, 95% CI 0.95
      5.66). Patients with cirrhosis also had a higher frequency (P < 0.05) of
      ADH2*1/*1 (100%) than blood donors (92%) and those with chronic pancreatitis
      (93%). The frequencies of genotypes of ALDH2, CYP2E1, GSTM1, GSTT1 and
      apolipoprotein E were similar in all groups. CONCLUSION: Alcoholic cirrhosis but
      not alcoholic chronic pancreatitis is associated with ADH3*2/*2 and perhaps with
      ADH2*1/*1. Both genes encode less active alcohol-metabolizing enzymes that may be
      associated with cirrhosis because of delayed formation of acetaldehyde (with
      higher intakes of alcohol), or diversion of alcohol metabolism through pathways
      other than ADH.

PMID- 11966949
TI  - Acute and 7-day portal pressure response to carvedilol and propranolol in
      cirrhotics.
AB  - BACKGROUND: Carvedilol, a non-selective beta- and alpha-1 blocking agent, has
      portal hypotensive action. This study evaluates the acute and 7-day response to
      carvedilol, and compares it to that of propranolol. METHODS: Thirty-six
      cirrhotics were randomized into two groups of 18 each, and treated with
      carvedilol or propranolol. Hepatic venous pressure gradient (HVPG) was measured
      before and 90 min after either 25 mg carvedilol or 80 mg propranolol was
      administered orally, and again 7 days after 12.5 mg carvedilol daily or 80 mg
      propranolol daily, respectively. 'Responders' were defined as those with HVPG
      reduction of > or = 20%. RESULTS: With carvedilol, 11/18(61.1%) and 11/17(64.7%)
      patients responded acutely and after 7 days, respectively, while 9/18(50%) and
      10/16(62.5%) did so to propranolol. However, HVPG reduction (percent) by
      carvedilol was not superior to that by propranolol either acutely (27.67 +/-
      31.49 compared to 22.98 +/- 27.40, P = 0.6) or after 7 days (28.2 +/- 29.05
      compared to 23.25 +/- 20.15, P = 0.6). With carvedilol, the acute HVPG response
      (P < 0.001) and responder status (P = 0.018) were good predictors of the response
      after 7 days, but were weak predictors in the case of propranolol (0.1 > P > 0.05
      and P = 0.059, respectively). On carvedilol, only one patient (with ascites)
      developed symptomatic systemic hypotension with oliguria. CONCLUSION: Carvedilol
      is a relatively safe, effective portal hypotensive agent, both acutely and over 7
      days, but not superior to propranolol, at least in Indians. The acute hemodynamic
      response seems promising in predicting long-term response.

PMID- 11966950
TI  - Incidence and clinical outcome of icteric type hepatocellular carcinoma.
AB  - BACKGROUND: To elucidate the incidence of the rare cases of icteric type
      hepatocellular carcinoma (IHCC), we conducted a retrospective study. The clinical
      outcomes of IHCC cases were also analyzed. METHODS: From January 1986 to December
      1997, newly diagnosed HCC cases were evaluated and reviewed from an admission
      registration database in a medical center. Patients who had HCC tumors which were
      located within biliary tracts, and caused obstructive jaundice as the initial
      clinical manifestation of HCC, were defined as cases of IHCC. Besides clinical
      manifestations, the outcomes and survival times of various treatment strategies
      among the IHCC cases were compared retrospectively. RESULTS: The incidence of
      IHCC was 0.53% (10/1897). The median age of the 10 IHCC patients (seven men,
      three women) was 56.1 years (range = 41-72 years). Most primary HCC lesions (80%)
      were of expansive type: either single nodular type or multinodular type. All the
      patients eventually died of cholangitis and sepsis. Besides biliary drainage,
      seven patients of moderate to good liver reserve function received transarterial
      chemoembolization (TACE) for palliative treatment, and three of these received
      additional radiotherapy (R/T) because of the limited effect of TACE (total dosage
      ranged from 1600 to 5000 cGy). One patient received only radiotherapy (total
      dosage 1600 cGy) because of having a single tumor and poor liver reserve
      function. The median survival time among those eight patients who received
      palliative treatment was 13.4 months (range = 8-26 months), which was
      significantly longer than for the other two patients without treatment (2 and 4
      months). CONCLUSIONS: Icteric type hepatocellular carcinoma (IHCC) is a rare
      presentation of HCC. Palliative treatment strategies, including TACE and/or R/T
      showed a beneficial effect in improving the survival time.

PMID- 11966951
TI  - Tumor necrosis factor-alpha and transforming growth factor-beta reflect severity
      of liver damage in primary biliary cirrhosis.
AB  - BACKGROUND AND AIMS: The pathogenesis of primary biliary cirrhosis (PBC) is
      unknown. The role of cytokines such as tumor necrosis factor-alpha (TNF-alpha)
      and transforming growth factor-beta (TGF-beta), and the effect of ursodeoxycholic
      acid (UDCA) in modifying the cytokine environment in patients with PBC has
      remained largely unstudied. Our aims were to determine: (i) the relationship
      between serum levels of TNF-alpha and TGF-beta and the severity of PBC; and (ii)
      the effects of UDCA therapy on TNF-alpha and TGF-beta levels in patients with
      PBC. METHODS: We studied 90 patients who had been treated with UDCA (53 patients)
      or placebo (37 patients) for 2 years as part of a randomized, double-blind,
      controlled trial. Patients were divided into histological stage I/II or stage
      III/IV disease. Serum TNF-alpha and TGF-beta levels were quantified by enzyme
      linked immunoabsorbent assay. RESULTS: Baseline levels of TNF-alpha were
      significantly greater in patients with stage III/IV compared to stage I/II
      disease. After 2 years of treatment with UDCA, patients showed a significantly
      greater decrease in TNF-alpha levels and progression risk score compared to
      placebo-treated patients. TNF-alpha and TGF-beta levels were significantly
      reduced compared to baseline levels in the UDCA-treated group after 2 years,
      while there was no significant change in the levels of placebo-treated patients.
      CONCLUSIONS: Serum TNF-alpha and TGF-beta levels may reflect severity of disease
      in patients with PBC. The beneficial effects of UDCA therapy may be explained by
      lowering serum levels of these two cytokines.

PMID- 11966953
TI  - Transplantation for cystic fibrosis: outcome following early liver
      transplantation.
AB  - BACKGROUND AND AIM: Life expectancy in patients with cystic fibrosis (CF) has
      recently improved due to numerous factors, including a multidisciplinary approach
      to their management. Prolonged survival may have led to an increasing impact of
      liver disease on the prognosis of CF patients. The aim of this study was to
      assess the role of liver transplantation in patients with CF. METHODS: The
      factors influencing outcome in 24 patients (15 adults and nine children) with CF
      who have received single liver transplantation, triple heart-lung-liver
      transplantation (tx) or died while being assessed for triple grafting, were
      analyzed. RESULTS: Median age at tx in single liver recipients (13 years) was
      lower than in triple graft recipients (21 years) and those who died (23 years).
      All patients who received single liver tx made an excellent recovery, including
      significant improvement of their respiratory function (mean forced vital capacity
      (FVC) increased from 61% before transplantation to 82% of expected, 6-9 months
      after tx). Four out of five patients who received triple tx died (0-2 months)
      after operation. On the basis of our retrospective review, we propose
      modifications to an existing scoring system for liver tx assessment in CF by
      scoring additional points for elevated white blood count, bilirubin, and impaired
      pulmonary function. These changes will need to be evaluated prospectively to
      confirm their predictive value. CONCLUSIONS: Liver transplantation is effective
      therapy in young patients with cystic fibrosis, portal hypertension and hepatic
      dysfunction, and is indicated before a critical stage of deteriorating lung
      function is reached. In patients with both end-stage liver and lung disease,
      triple tx has a poor prognosis. Pre-emptive liver tx in younger patients with CF
      not only has a better outcome but improves lung function.

PMID- 11966952
TI  - Disease recurrence after liver transplantation in Western Australia.
AB  - BACKGROUND AND AIM: Orthotopic liver transplantation (OLT) is now the accepted
      therapy for end-stage chronic liver disease. Long-term survival is now expected
      in the majority of patients and, consequently, disease recurrence has emerged as
      a major concern. Our aim was to document the rate of disease recurrence after
      liver transplantation for conditions other than hepatitis C, in patients followed
      up by the Western Australian Liver Transplant Service (WALTS). METHODS: The case
      notes of all post-OLT patients followed up by WALTS were reviewed. Patients were
      excluded if survival was less than 3 months post-OLT; OLT was performed for
      hepatitis C alone or follow up was unavailable. Detection and definition of
      disease recurrence depended on pretransplant diagnosis, and were based on patient
      interview, biochemical, immunological and serological tests. Radiological and
      histological confirmation were obtained where clinically indicated. RESULTS:
      Eighty-seven patients were identified (89 OLTs performed). The overall rate of
      recurrence was 10%. Recurrence rates by disease were: primary sclerosing
      cholangitis (17%), primary biliary cirrhosis (12%), autoimmune hepatitis (17%),
      hepatitis B (40%) and alcoholic liver disease (4%). Alcohol use relapse after
      transplantation occurred in 25%. The overall survival post-OLT was 87%, with a
      mean follow up of 53 months. Survival in patients with recurrent disease was 89%.
      CONCLUSIONS: Disease recurrence after OLT does occur, but overall, it is
      relatively uncommon. Recurrence rates vary significantly and depend, in part, on
      indication for OLT. With medium-term follow up, recurrent disease does not have
      an effect on mortality.

PMID- 11966954
TI  - Gastrointestinal: tracheal involvement from esophageal cancer.

PMID- 11966955
TI  - Hepatobiliary and pancreatic: a disoriented woman. A large paraumbilical vein.

PMID- 11966958
TI  - MALToma versus marginal zone lymphoma versus diffuse large B cell lymphoma.

PMID- 11966956
TI  - Overlap of idiopathic portal hypertension and scleroderma: report of two autopsy
      cases and a review of literature.
AB  - Idiopathic portal hypertension (IPH) is characterized by dense fibrosis of portal
      tracts and portal venous obliteration. Little is known about the etiopathogenesis
      of IPH. Association of various autoimmune diseases such as systemic lupus
      erythematosus in IPH suggests that IPH may share immunological disturbances with
      such autoimmune diseases. We recently experienced two autopsy cases presenting
      with both diffuse scleroderma and IPH. Dense fibrosis was found in both the
      dermis and intrahepatic portal tract of these cases. In addition, small vascular
      damages were commonly observed to various degrees in these fibrotic areas of both
      organs. The activation of fibroblasts and vascular damages mediated by various
      growth factors and cytokines reportedly involved in the dermis in scleroderma
      might have also been operative in portal tracts in these two cases of IPH. A
      review of literature disclosed eight overlapping cases of IPH and scleroderma
      (middle- to old-aged females), and scleroderma was diagnosed earlier than IPH.
      These findings suggest that similar pathogenetic processes are operative in the
      dermis as well as in the portal tracts of the liver in these cases.

PMID- 11966960
TI  - Case of liver metastasis from colon cancer successfully treated by regional
      chemotherapy with mitomycin C alone.

PMID- 11966962
TI  - The effects of a novel Bioglass dentifrice on dentine sensitivity: a scanning
      electron microscopy investigation.
AB  - Dentine sensitivity (DS) is a common condition which affects 8-35% of the
      population. Both In-Office and Over-the-Counter products have been used in
      treatment, usually occluding open dentine tubules on the exposed root surface.
      Currently there appears to be no ideal material which permanently occludes
      dentine tubules. Bioactive and biocompatible glasses are known to induce
      osteogenesis in physiological systems and may offer suitable materials for
      surface reactivity which could theoretically occlude tubules. A new dentifrice
      formulation containing a modified Bioglass material replacing part of the
      abrasive silica component was compared with original 45S6 bioactive glass.
      Dentine discs were treated with original Bioglass, three coded dentifrices
      containing 0, 2.5 and 7.5% Bioglass and two further selected dentifrice products.
      These specimens were prepared for scanning electron microscopy (SEM) and viewed
      in a Cambridge stereoscan 90B. The results demonstrated that original bioactive
      glass particles covered the dentine surface and/or occluded dentine tubules,
      although this original formulation was easily dislodged. Dentifrice with
      different ratios of added Bioglass was assessed to provide greater surface
      coverage and tubule occlusion than without Bioglass. It was concluded that the
      inclusion of bioactive glass particles in a suitably formulated vehicle may be an
      effective agent for the treatment of dentine sensitivity.

PMID- 11966963
TI  - Structure-property relationship of cast Ti-Nb alloys.
AB  - The present work is a study of the microstructure, mechanical properties and
      corrosion behaviour of a series of binary Ti-Nb alloys with Nb contents up to 35
      wt%, with emphasis placed on the structure-property relationship of the alloys.
      The results indicate that crystal structure and morphology of the Ti-Nb alloys
      are sensitive to the Nb content. The cast c.p. Ti has a hexagonal alpha phase
      with a lath type morphology. The alloys containing 15 wt% or less Nb are
      dominated by a hexagonal alpha' phase with an acicular, martensitic structure.
      When containing 17.5-25 wt% Nb, the alloys are primarily comprised of an
      orthorhombic alpha" phase. With 27.5 wt% Nb, metastable beta phase starts to be
      retained. With Nb contents higher than 30 wt%, the equi-axed beta phase is almost
      entirely retained. Small amounts of omega phase are detected in alloys containing
      27.5 and 30 wt% Nb. Among all present alloys, Ti-10Nb and Ti-27.5Nb exhibit the
      highest strengths, while the alpha"-dominated (17.5 and 20Nb) and beta-dominated
      (> 30Nb) alloys have the lowest moduli. All Ti-Nb alloys show excellent corrosion
      resistance in Hank's solution at 37 degrees C. From the present data, the
      microhardness, bending strength and modulus of the various phases in Ti-Nb alloys
      are compared and tentatively summarized as follows: Microhardness: omega > alpha'
      > alpha" > beta > alpha (c.p. Ti) Bending strength: omega > alpha' > alpha" >
      beta > alpha (c.p. Ti) Bending modulus: omega > alpha (c.p. Ti) > alpha' > alpha"
      > beta

PMID- 11966965
TI  - Bond strengths of five tapered root posts regarding the post surface.
AB  - The advantage of tapered passive root posts is their homogenous force
      transmission without creating stress peaks on the root surface because of their
      anatomical root form. However, their expected retentive strengths are low
      compared with the other post systems. The objective of this in vitro study was to
      determine the retentive strengths of five tapered post systems from different
      manufacturers using tensile tests. For this purpose, all posts were cemented with
      zinc phosphate cement (Tenet) into the roots of 50 intact anterior teeth
      according to the manufacturer's instructions for each system. The contact surface
      area between the root canal wall and the post was taken into account in the
      calculations in order to obtain comparable results for different post
      configurations. The highest bond strength values were achieved for the Erlangen
      post system (10.8 N mm(-2)) and MP Pirec post system (10 N mm(-2)). These values
      were more than three times those of the Velva-Post (3.2 N mm(-2)) and the
      Cylindro-Conical system (3.5 N mm(-2)) and five times more than those of the Dr
      Mooser post system (1.7 N mm(-2)). The bond strength values of the Erlangen post
      system, Cylindro-Conical system and Dr Mooser post system showed statistically
      significant differences compared with the other groups. The results of this study
      indicated that the bond strengths of tapered posts were not only affected by the
      contact surface but also by the taper angle, shape of the post system, the width
      of the cement joint, surface roughness of the posts as well as the form of the
      canal wall. In clinical practice, in case of choosing tapered posts with similar
      shapes, retention may still vary because of other factors.

PMID- 11966964
TI  - Occlusal conditions just after the relief of temporomandibular joint and
      masticatory muscle pain.
AB  - When the signs and symptoms of temporomandibular joint disorders (TMD) are
      present, it is possible that occlusal conditions and mandibular movements are
      changed. Accordingly, the presence of occlusal interferences may be misjudged. It
      is therefore reasonable to consider that occlusal conditions should be examined
      just after the relief of symptoms. The comparison of occlusal conditions in 52
      temparomandibular joint (TMJ) pain patients and 27 muscle pain patients with that
      in 60 asymptomatic controls was made. Occlusal examination in the patients was
      administered just after the relief of pain by bite plane therapy alone. The only
      occlusal factor which was associated with pain symptoms was no canine contact on
      the working side on laterotrusion. It is suggested therefore that further studies
      as regards this type of interference should be performed.

PMID- 11966966
TI  - Changes of blood flow in the mucosa underlying a mandibular denture following
      pressure assumed as a result of light clenching.
AB  - The aim of this study was to investigate the influence of the continuous
      compression assumed as a result of light clenching on the blood flow of the
      denture underlying mucosa in tissue-supported or tooth-tissue-supported denture
      wearers. Measurements were carried out on eight removable partial denture wearers
      (three males and five females, from 50 to 72 years, mean age: 61.5 years). The
      blood flow in the denture underlying mucosa was measured at the unilateral
      mandibular first molar region using an experimental denture base equipped with a
      laser Doppler flowmeter. The area of the experimental denture base was 2 cm2, and
      the loading force was 1 kgf. The loading time was set at 5, 10, 20, 30 and 60 s.
      The blood flow after 20 s loading was <15% in rest. The times from release of
      loading to the maximum blood flow and from release of loading to recovery up to
      110% of the blood flow at pre-loading were significantly prolonged by an increase
      in the loading time. Even if it is light, a continuous clenching results in
      ischaemia and delays the recovery of blood flow in the mucosa underlying the
      denture after release of compression.

PMID- 11966968
TI  - Finite element stress analysis of the effect of short implant usage in place of
      cantilever extensions in mandibular posterior edentulism.
AB  - Although the destructive effect of cantilevered implant supported fixed partial
      prosthesis is well known, in some cases usage of cantilever extension seems to be
      inevitable for many clinicians. The purpose of this study was to evaluate the
      effect of additional placement of a shorter implant in place of a cantilever
      extension on stress distribution compared with cantilevered fixed prosthesis in
      mandibular posterior edentulism. A mandibular Kennedy II finite element model was
      constructed. Six different implant supported fixed partial prosthesis were
      designed according to two main configurations; anterior and posterior cantilever
      extensions compared with the placement of additional shorter implant
      configurations. An oblique occlusal load of 400 N was applied. Tensile and
      compressive stress values in the cortical bone surrounding the cervical regions
      of implants and Von Misses stress values in the implants were evaluated.
      Significant lower stress values were recorded at the shorter implant placement
      configurations compared with the cantilevered prosthesis. Posterior cantilever
      extension performed higher stress values than the anterior counterpart. In
      clinical applications where cantilevered fixed partial prosthesis seems to be
      inevitable because of anatomical restrictions and/or complications such as loss
      of implant, an additional placement of a shorter implant should be considered.

PMID- 11966967
TI  - Vibration analysis of maxillary removable partial denture frameworks.
AB  - The purpose of this study was to investigate the vibratory characteristics of
      three designs of the Class I Kennedy maxillary removable partial denture
      frameworks as the basic study. Their major connectors comprised a U-shaped
      palatal connector (UPC), single palatal bar (SPB), and anterior-posterior palatal
      bars (APB). Frequency response functions were measured when the framework was
      impacted. The modal shape was observed and the decay rate was calculated using
      modal analysis software. The results showed that the vibratory properties of each
      framework differed from each other. Within the range of frequencies from 10 to
      2000 Hz, the UPC type had seven natural frequencies, while the SPB and the APB
      types had six. The UPC type had a greater number of natural modes accompanied by
      elastic deformation, including fluttering and twisting, than the other type, and
      the UPC type was considered to be unfavourable. The decay rate of the APB type
      was significantly higher than those of the UPC and the SPB types (P < 0.01).

PMID- 11966969
TI  - Effect of wash bulk on the accuracy of polyvinyl siloxane putty-wash impressions.
AB  - Variations in the bulk of wash in a putty-wash impression technique can result in
      dimensional changes proportional to the thickness of the wash material during
      setting. The purpose of the study was to determine the amount of wash necessary
      to achieve accurate stone models while using a two-step putty-wash impression
      technique with polyvinyl siloxane (PVS) impression material. A total of 45
      impressions were made of a stainless steel master model, 15 impressions for each
      wash thickness (1, 2 and 3 mm). The model contained three full-crown abutment
      preparations, which were used as the positive control. Accuracy was assessed by
      measuring six dimensions (occlusogingival and interabutments) on stone dies
      poured from impressions of the master model. One-way analysis of variance (ANOVA)
      showed statistically significant differences amongst the three wash bulk groups,
      for all occlusogingival and interabutment measurements (P < 0.001). The overall
      discrepancies of the groups using wash thickness of 1 and 2 mm were smaller than
      the group with 3 mm wash thickness. Therefore, wash bulks of 1 and 2 mm were most
      accurate for fabricating stone dies, using PVS impression materials. This can be
      achieved by using the temporary crown to create the desired wash space in the
      preliminary putty impression. Wash thickness > 2 mm was inadequate to obtain
      accurate stone dies.

PMID- 11966970
TI  - Effectiveness of exercise therapy in patients with myofascial pain dysfunction
      syndrome.
AB  - Twenty consecutive patients suffering from myofascial pain dysfunction (MPD) were
      assigned to a waiting-list, serving as a no-treatment control period. Inclusion
      criteria were: (i) pain in the temporomandibular region for at least 3 months,
      (ii) no evidence of internal derangement or osteoarthritis and (iii) symptoms of
      postural dysfunction. Treatment consisted of active and passive jaw movement
      exercises, correction of body posture and relaxation techniques. The following
      main outcome measures were evaluated: (i) pain at rest, (ii) pain at stress,
      (iii) impairment, (iv) mouth opening at base-line, before and after treatment and
      at 6-month follow-up. All patients completed the study and no adverse effects
      occurred. During control period no significant changes occurred. After treatment
      six patients had no pain at all (chi-square: P < 0.01) and seven patients
      experienced no impairment (chi-square: P < 0.005). Pain at stress, impairment and
      incisal edge clearance improved significantly (Wilcoxon test P < 0.001). This
      result did not change until follow up, except pain at stress, which further
      improved significantly (Wilcoxon test P < 0.03). At follow up 16 patients
      experienced no pain at all, 13 patients were not impaired and only three patients
      had a restricted mouth opening, in contrast to 12 before treatment (chi-square
      test P < 0.001). CONCLUSION: Exercise therapy seems to be useful in the treatment
      of MPD Syndrome.

PMID- 11966971
TI  - The effect of ambient light on QLF analyses.
AB  - The use of optical methods in the diagnosis of early caries is developing
      rapidly. The introduction of the quantitative light-induced fluorescence (QLF)
      device has promised the use of a quantifiable technique in vivo. This study
      describes the effect that ambient light has upon the reliability of QLF analyses.
      Using human teeth and simulated lesions the study examined the effect of 15
      different light levels on three severities of carious lesions. The study found
      that a light level of 88 lux could be employed in areas where QLF is to be used
      without significantly affecting the reported value, DeltaQ. This study impacts
      upon the health and safety issues surrounding QLF usage as well as ethical issues
      relating to working in dark environments.

PMID- 11966972
TI  - Clinical TMD, pain-related disability and psychological status of TMD patients.
AB  - This study investigated the clinical temporomandibular disorders (TMD), pain
      related disability and psychological status of TMD patients using a computerized
      on-line TMD diagnostic system (NUS TMD v1.1). A total of 107 patients (32 male,
      75 female) referred to the TMD clinics at the National Dental Centre and National
      University Hospital participated in this study. The mean age of the predominantly
      Chinese population (82.2%) was 30.8 years (range from 12 to 64 years). The
      history questionnaire and clinical examination were input directly into computers
      by patients and clinicians. A 'Summary of Findings' was then immediately
      generated by the program based on Axis I and II rules. The data was subsequently
      exported to SPSS for statistical analysis. About 20.6% of the patients had
      myofascial pain but only 7.5% experienced limited mandibular opening associated
      with myofascial pain. The majority of patients (> 80%) did not suffer from disc
      displacements (right and left joints). The frequency of arthralgia was also low
      (right joint 8.4%; left joint 7.5%) and only one patient had osteoarthosis of the
      TMJ. About 78.5% of the patients had low disability with almost equal
      distribution between low and high intensity pain, 27.1% of the patients were
      moderately depressed and 11.2% had severe depression. No significant difference
      in limitations related mandibular functioning scores was observed between
      normal/depressed patients and between patients with the different graded chronic
      pain severity classification. The three most frequent jaw disabilities were:
      eating hard foods (77.6%), yawning (75.7%) and chewing (64.5%). NUS TMD v1.1 is
      an extremely useful tool in the diagnosis/research of clinical TMD.

PMID- 11966973
TI  - A calculation of stress distribution in metal-porcelain crowns by using three
      dimensional finite element method.
AB  - The objective of this study was to calculate stress distribution in a maxillary
      second premolar tooth which occurred by the mastication force. The tooth model
      was crowned with Au-Pd alloy, Ni-Cr alloy and porcelain. A load of 450 N, at an
      angle of 45 degrees to the longitudinal axis was applied on the occlusal margin
      of the crown tooth. The tooth was assumed isotropic, homogenous, elastic and
      unsymmetrical. This numerical study was carried out using three-dimensional
      finite element models and calculation programs were prepared by the authors using
      FORTRAN 77. The distribution of compressive, tensile and shear stress were
      plotted for the dentine, dentine-metal and metal-porcelain interfaces. The
      highest stress values were observed when Ni-Cr alloy and porcelain was used.

PMID- 11966974
TI  - Influence of visible-light exposure on colour stability of current dual-curable
      luting composites.
AB  - This study was conducted to evaluate influence of visible-light exposure on
      colour stability of dual-curable luting composite. Using six dual-curable luting
      composites [Bistite II (BI), Clapearl DC (CL), Dicor Light Activated Cement (DI),
      G-Cera Cosmotech II (GC), Lute-It (LU) and Variolink II (VA), disk specimens were
      prepared with the following two methods: (i) dual-cured specimens, exposure with
      visible-light from a photo-curing unit for 120 s and (ii) chemical-cured
      specimens, chemically cured without exposure. Five specimens were produced for
      each material and curing mode. After 24 h, all specimens were immersed in
      distilled water at 37 degrees C for 24 weeks, during which colour accuracy was
      measured with a dental colorimeter. The colours characterized in the Commission
      Internationale d'Eclairage (CIE) L*a*b* colour space were first determined 24 h
      after preparation (baseline colour evaluation), and again after 1, 2, 3, 4, 8,
      12, 16 and 24 weeks. The colour difference (Delta E*) values between 24 h and the
      other immersion periods were calculated, and then analysed by repeated measure
      analysis of variance (ANOVA). In addition, the Delta E* values after 24 weeks for
      dual-cured specimens were compared with those for chemical-cured specimens by one
      way ANOVA and by contrasts for each composite (P < 0.05). The Delta E* values
      were influenced by the material and curing mode as well as immersion period
      (P=0.0001). After 24 weeks the dual-cured specimens showed significantly lower
      Delta E* values than the chemical-cured specimens, except for the VA material.
      The CL material exhibited the least colour change (1.9 +/- 0.2) among the dual
      cured specimens, and the VA material showed the least (4.5 +/- 0.9) among the
      chemical-cured specimens after 24 weeks. Dual-curable luting composites should be
      polymerized with the dual modes to ensure colour stability.

PMID- 11966975
TI  - The influence of the location of load transfer on strains around implants
      supporting four unit cement-retained fixed prostheses: in vitro evaluation of
      axial versus off-set loading.
AB  - Prudent control of the biomechanical load on dental implants is imperative to
      achieve long-term clinical success. The design of the final prosthesis and
      location of force transmission have a definitive influence on the quantification
      of induced strains and load partitioning among implants. While axial loading of
      implants generate an even distribution of stresses in the bone around implants,
      off-set loading, which is particularly observed in screw retained prosthesis
      increases the stresses at the bone-implant interface. This study evaluated the
      cervical strains on dental implants supporting four unit cement retained fixed
      prostheses under 50 N static axial and off-set loading conditions. As the type of
      strains are also dependent on the point of load transfer, design of the
      prosthesis and implant positioning, the study comprised the evaluation of induced
      strains through a simulation of five cement retained prosthetic options. The
      results revealed that off-set loading increases the magnitude of strains.
      However, it was not significant for all configurations (P < 0.05). This finding
      emphasizes the accompanying effect of implant location, angulation and
      macrogeometry of the prosthesis and, that the biomechanical evaluation of
      affecting factors is a multifaceted phenomenon.

PMID- 11966976
TI  - Purification and characterization of charantin, a napin-like ribosome
      inactivating peptide from bitter gourd (Momordica charantia) seeds.
AB  - A peptide designated charantin, with a molecular mass of 9.7 kDa, was isolated
      from bitter gourd seeds. The procedure comprised affinity chromatography on Affi
      gel blue gel, ion-exchange chromatography on Mono S and gel filtration on
      Superdex 75. The N-terminal sequence of charantin exhibited marked similarity to
      that of the 7.8-kDa napin-like peptide previously isolated from bitter gourd
      seeds. Charantin inhibited cell-free translation in a rabbit reticulocyte lysate
      system with an IC50 of 400 nm, a potency lower than that of the previously
      reported small ribosome-inactivating protein gamma-momorcharin (IC50 = 55 nm)
      which also exhibited an abundance of arginine and glutamate/glutamine residues.
      Charantin reacted positively in the N-glycosidase assay, yielding a band similar
      to that formed by the small ribosome-inactivating proteins gamma-momorcharin and
      luffin S.

PMID- 11966977
TI  - Synthesis and biological evaluation on hMC3, hMC4 and hMC5 receptors of gamma-MSH
      analogs substituted with L-alanine.
AB  - To elucidate the molecular basis of the interaction of the native dodecapeptide
      gamma-MSH with the melanocortin receptors, we performed a structure-activity
      study in which we systematically replaced l-Ala in each position of this peptide.
      Here we report the binding affinity and agonist potency on human MC3R, MC4R and
      MC5R. Intracellular cAMP concentration was measured on CHO cells, and binding
      assays were carried out using membranes prepared from these cell lines which
      stably express hMC3R, hMC4R and hMC5R. Our results indicate that the last four
      amino acids in the C-terminal region of gamma-MSH are not important determinants
      of biological activity and selectivity at human melanocortin receptors.
      Interesting results were obtained when l-Ala was substituted for His6, Phe7, Arg8
      and Trp9. For these peptides, the affinity and activity at all three human
      receptors (MC3R, MC4R and MC5R) decreased significantly, demonstrating that the
      His-Phe-Arg-Trp sequence in gamma-MSH is important for activity at these three
      melanocortin receptors. Similar results were obtained when Met3 was replaced with
      l-Ala, suggesting the importance of this position in the interaction with all
      three receptors. This study highlights the role played by the His-Phe-Arg-Trp
      sequence in receptor binding and in agonist activity of gamma-MSH.

PMID- 11966979
TI  - Probing degeneracy in antigen-antibody recognition at the immunodominant site of
      foot-and-mouth disease virus.
AB  - Antigen-antibody binding is regarded as one of the most representative examples
      of specific molecular recognition in nature. The simplistic view of antigenic
      recognition in terms of a lock-and-key mechanism is obsolete, as it is evident
      that both antigens and antibodies are flexible and can undergo substantial mutual
      adaptation. This flexibility is the source of complexities such as degeneracy and
      nonadditivity in antigenic recognition. We have used surface plasmon resonance to
      study the effects of combining multiple amino acid replacements within the
      sequence of the antigenic GH loop of foot-and-mouth disease virus. Our aim was 2
      fold: to explore the extent to which antigenic degeneracy can be extended in this
      particular case, and to search for potential nonadditive effects in introducing
      multiple amino acid replacements. Combined analysis of one such multiply
      substituted peptide by SPR, solution NMR and X-ray diffraction shows that
      antigenic degeneracy can be expected as long as residues directly interacting
      with the paratope are conserved and the peptide bioactive folding is unaltered.

PMID- 11966978
TI  - Effect of viscosity on the deamidation rate of a model Asn-hexapeptide.
AB  - The effect of viscosity on the deamidation rate of a model Asn-containing
      hexapeptide (l-Val-l-Tyr-Pro-l-Asn-Gly-l-Ala) was assessed in aqueous solution
      and in solids containing varying amounts of poly(vinyl pyrrolidone) (PVP) and
      water. Stability studies were conducted at 0.1 mg/mL peptide and 0-50% PVP (w/w)
      in aqueous solution, and at 5% (w/w) peptide and different relative humidities
      (31.6, 53.1, 74.4 and 96%) in the solid state. The parent peptide and its
      deamidation products were analysed by reverse-phase high-performance liquid
      chromatography. Deamidation rates decreased with increasing solvent viscosity in
      a manner described by a semi-empirical mathematical model developed to describe
      this relationship. The results suggest that the motion of the Asn side-chain
      along the reaction coordinate is a function of the macroscopic solvent viscosity.
      However, the apparent energy barrier for the diffusive movement of the side-chain
      appears to be less than the energy barrier for that associated with macroscopic
      viscosity. The dependence of the deamidation rate on viscosity in both viscous
      solution and hydrated solids further demonstrates the importance of mobility in
      peptide deamidation.

PMID- 11966980
TI  - Analogs of Substance P modified at the C-terminus which are both agonist and
      antagonist of the NK-1 receptor depending on the second messenger pathway.
AB  - The initial goal of this study was to analyze, using photolabeling, the
      interactions between Substance P and its tachykinin NK-1 receptor. Therefore, the
      photoreactive amino acid para-benzoyl-phenylalanine (pBzl)Phe was incorporated
      into the Substance P sequence from position 4 to 11 leading to
      Bapa0[(pBzl)Phex]SP analogs. Biotinyl sulfone-5-aminopentanoic acid (Bapa) was
      introduced in order to purify the covalent complex. These photoreactive SP
      analogs were first assayed for their affinity for the two binding sites
      associated with the NK-1 receptor, as well as for their potency in activating the
      phospholipase C and adenylate cyclase pathways. All analogs photoreactive from
      position 4 to 11 have moderate to high affinity for the two NK-1 receptor-binding
      sites, except for the analog modified at position 7. This affinity could be
      correlated to their potency to activate the phospholipase C and adenylate cyclase
      pathways, except for the analog photoreactive at position 11.
      Bapa0[(pBzl)Phe11]SP was found to be an agonist in the phospholipase C pathway
      and an antagonist in the adenylate cyclase pathway, other analogs modified at
      position 11 were therefore analyzed. Among these, Bapa0[Pro9, (pBzl)Hcy(O2)11]SP
      is a partial agonist, whereas Bapa0[Hcy(ethylaminodansyl)11]SP is a full agonist
      in the phospholipase C pathway, the two analogs being antagonist in the adenylate
      cyclase pathway. These results show that analogs of SP can be simultaneously
      agonist at one binding site and antagonist at the other binding site associated
      with the NK-1 receptor.

PMID- 11966981
TI  - Mental health work observed: a comparison of the perceptions of psychiatrists and
      mental health nurses.
AB  - This study explores mental health nurses' and psychiatrists' perceptions of their
      work. It was carried out in five mental health Trusts in the West Midlands, UK.
      Three groups were surveyed: psychiatrists, hospital-based nurses and community
      mental health nurses (CMHNs). Results showed that CMHNs' sources of job
      satisfaction and dissatisfaction were more similar to those of psychiatrists than
      to those of their hospital-based counterparts. All three groups cited the
      intrinsic worthwhileness of their work, autonomy, the scope for creativity, the
      variety their job offered and their contact with clients as contributing to their
      overall job satisfaction. Hospital-based nurses listed the support they received
      from colleagues as their second source of job satisfaction, whereas CMHNs and
      psychiatrists cited the provision of care to patients. Excessive administrative
      duties and the absence of or poor quality of management were perceived by all
      three groups as sources for dissatisfaction with their work. Hospital nurses
      cited job insecurity as a principal concern more frequently than CMHNs and
      psychiatrists. The paper concludes by discussing recommendations for changes to
      improve the nature of the work in mental health services and in the work
      environment. Changes must reflect the concerns of the different groups of mental
      health professionals.

PMID- 11966982
TI  - Should patients who assault staff be prosecuted?
AB  - This article discusses the issue of prosecution of mentally disordered patients
      particularly in relation to assaults or acts of violence in health care settings.
      The arguments for prosecuting those responsible for committing acts of dangerous
      behaviour are discussed, as are the arguments against prosecution and some of the
      possible reasons why this is a contentious area of discussion. There are
      significant risks to the integrity of mental health services if the consideration
      of prosecution as a strategy to reduce risk of violence in hospitals does not
      become an area of meaningful discussion at all levels. The risk of violence is
      real, but the risks of accepting it without taking measures to reduce the
      frequency or severity of violence is no less acceptable than accepting that
      burglary is inevitable and leaving one's front door ajar every day. Health care
      professionals may wish to consider that in the absence of a clinically based
      solution or ownership of the problem, the risk of an organizational response to
      this sensitive area, perhaps guided or driven by political concerns is likely, as
      has happened in areas such as risk assessment, treatability and compliance with
      treatment.

PMID- 11966983
TI  - 'But what about the really ill, poorly people?' (An ethnographic study into what
      it means to nurses on medical admissions units to have people who have harmed
      themselves as their patients).
AB  - In the UK, someone dies by suicide every 2 hours. An increasing number are also
      harming themselves. Many of these people are admitted to Medical Admissions Units
      of General Hospitals. Department of Health guidelines now recommend that anyone
      who harms him or herself should have a psychosocial and risk assessment. This
      means that they have to stay in hospital until they are assessed and this renders
      them 'different' from other patients. This study uses an ethnographic approach to
      search for the meaning to nurses of having this group of patients on the ward,
      using participant observation and semistructured interviews with four nurses.
      Three themes were isolated through analysis of the data: the busy quality of such
      wards (busyness) how this group of clients impede the busy quality and the
      strategies which nurses use to cope with the difficulties. Analysis of the data
      revealed that the research participants found difficulty in understanding why
      people harm themselves and that they felt that they did not have the requisite
      skills to deal with this group of people. This appears to leave them with a sense
      of frustration and helplessness which perhaps mirrors that of this client group.

PMID- 11966984
TI  - Non-incarcerated psychopaths: why we need to know more about the psychopaths who
      live amongst us.
AB  - On 1 November 2000, Robert Stewart, aged 20, was jailed for life for bludgeoning
      to death his Asian cellmate, Zahid Mubarek, aged 19 years because 'he felt like
      it'. During the court hearing the term 'psychopathic personality' was used in
      relation to Stewart and, following this and other similar cases, the average man
      or woman could be forgiven for believing that psychopathy is inextricably linked
      with dangerousness and criminality. In the light of the Government consultation
      paper entitled Managing Dangerous People with Personality Disorder. Proposals for
      Policy Development and the Government White Paper Reforming the Mental Health Act
      -- Part II: High-risk patients, this article proposes that whilst studies
      conducted with incarcerated psychopaths will continue to increase our knowledge
      and understanding of criminality, non-incarcerated psychopaths have an arguably
      equal potential to illuminate our understanding of the emotional difficulties,
      such as lack of empathy and lack of conscience, which underlie psychopathy and
      which lead to offending behaviour. Although a range of obstacles have hindered
      progress in this field of study, this paper proposes that developing an
      understanding of the nature of the emotional difficulties of the psychopath,
      unconfounded by criminality, has the potential to make a valuable contribution to
      the field of child psychiatry in ways which have implications for mental health
      nurses and society as a whole. It theorizes that if the psychological constructs
      which underlie psychopathy were better understood, children who display those
      emotional difficulties could be more accurately identified and strategies be
      generated which carry the ultimate aim of minimizing the risk of those children
      developing the offending behaviour associated with psychopathy.

PMID- 11966985
TI  - African and African Caribbean users' perceptions of inpatient services.
AB  - It has been suggested that well-documented differences in African and African
      Caribbean people's contact with mental health services may stem from the
      organization, processes and practices of services themselves. This article
      presents the findings of a qualitative study which explored the inpatient
      experiences of a sample of African and African Caribbean people. Although some
      positive experiences were described, in the main, participants' accounts revolved
      around a sense of loss of control and around experiences of overt and implicit
      racism. Underpinning these experiences were relationships with staff that were
      perceived to be unhelpful. On the basis of both the positive and negative
      experiences described, we draw conclusions about the changes required to ensure
      that inpatient services more effectively meet the needs of this group.

PMID- 11966986
TI  - Suicide: a personal reflection.
AB  - One of the authors of this paper, Carla Diedrich, had a personal experience of
      suicide in her family. She wants to both share the experience and allow the
      circumstances to be directive and informative for individuals who have had
      similar experiences with suicide and for those working in a clinical capacity. In
      this sense, the work belongs to Carla and her family and has been significant,
      almost cathartic, in helping her especially deal with this difficult set of
      personal circumstances.

PMID- 11966987
TI  - Community mental health nurses and authority to prescribe medications: the way
      forward?
AB  - This paper explores a single dimension of the nurse practitioner role - whether
      community mental health nurse practitioners should have authority to prescribe
      medications. The paper is taken from a larger study about how these nurses
      promote wellness with clients experiencing an early episode of psychotic illness.
      The focus is timely as several Australian States have recently passed nurse
      practitioner legislation. This qualitative study used interviews and participant
      observation to collect data. The fieldwork was undertaken in the community, in
      regional and rural New South Wales, Australia and involved community mental
      health nurses. The findings show that expanding the nurse practitioner role to
      include authority to prescribe medications is currently contentious. Respondents
      envisaged that prescribing authority would include most medications that are used
      to treat mental illness but exclude drugs that treat medical illness. They
      identified a need for an appropriate educational course, and called for a system
      of clinical supervision and ongoing support for nurses assuming this role.
      Participants also claimed that individual nurses who choose to forgo prescribing
      authority should not be coerced into undertaking this role. The findings have
      professional, clinical, legal and educational implications for nurses as they
      seek authority to prescribe within the context of a nurse practitioner role and
      these are discussed.

PMID- 11966988
TI  - Social network and social support characteristics amongst individuals recently
      discharged from acute psychiatric units.
AB  - This study compares the social support network of a diagnostically heterogeneous
      group of community mental health service users recently discharged from acute
      inpatient units, with that of a mental health service user comparison group with
      no history of hospital admission. Social data were elicited by a structured
      interview schedule (the Social Network Schedule). It was observed that the study
      group was characterized by smaller overall social networks, particularly within
      the primary network, but conversely the group had a greater proportion of service
      user peer contact. Few differences in perceived social support between groups
      were observed, although the study group reported fewer confidants. The
      implications of the study for nursing staff are discussed.

PMID- 11966989
TI  - Youth employment, mental health and substance misuse: a challenge to mental
      health services.
AB  - Employment is the cornerstone of social inclusion, the means by which individuals
      play a full and active part in society and has a pivotal role in helping young
      people to negotiate the transitional period between the child and adulthood.
      Employment therefore should be seen as a right and given a higher priority by
      health and social care agencies. There are numerous difficulties preventing some
      young people from achieving full employment and these are compounded for young
      people with concurrent mental health and substance misuse problems (dual
      diagnosis). The coexistence of these two problems is on the increase and they are
      recognized as significant barriers to employment. Unemployment may lead to social
      alienation, criminal or other antisocial activity and a higher incidence of
      suicide. Consequently, there is a danger of young unemployed people slipping into
      a spiral of self-defeating, antisocial and risky behaviour. There is little
      evidence of health and social care agencies working in partnership with voluntary
      sector organizations to tackle the growing problem of dual diagnosis and youth
      unemployment, although there are obvious linkages between employment,
      psychological health, social inclusion and substance misuse. It is therefore
      worth exploring the issues surrounding work, mental health and substance misuse
      in young people if we are to generate new ways of thinking about and responding
      to the needs of this target group. This presents a challenge to mental health
      services, particularly nurses who face the impact of these issues in their day to
      day practice but often lack the preparation and support to adequately address
      them.

PMID- 11966990
TI  - HOVIS -- The Hertfordshire/Oxfordshire Violent Incident Study.
AB  - Violence in psychiatric inpatient units is a major and growing problem. Research
      interest has primarily focussed on patient characteristics. The role of staff
      factors and the antecedents of violent incidents has been neglected, despite the
      fact that staff factors and behaviour may be more readily amenable to change than
      patient characteristics. The HOVIS study sought to obtain the views of a sample
      of mental health nurses in current clinical practice about staff-related factors,
      which they perceive to contribute to, or protect against, the occurrence of
      violent incidents. A total of 108 nurses working in psychiatric acute admission,
      intensive care and low secure units, in two NHS Trusts were interviewed using a
      specially designed semistructured interview schedule. These nurses identified a
      variety of behaviours, clinical skills, personal characteristics and
      interpersonal skills that they believe impact on the occurrence of violent
      incidents. These findings are discussed in relation to their possible training
      and managerial implications.

PMID- 11966992
TI  - The impact of a practice development project on the quality of in-patient small
      group therapy.
AB  - In 1993 a mental health service in South-east England initiated a practice
      development project that aimed at continuously improving the quality of in
      patient small group therapy provided within its four acute wards. From the outset
      it was intended that the project and the practice it focused on should be robust
      and research based. In support of this an evaluative study was carried out in
      1998. The evaluation covered a 6-month period and coincided with concerns being
      reported elsewhere about the adequacy of therapeutic activity within acute
      psychiatric settings across the country. Data collected for the evaluation
      focused on the quality dimensions of effectiveness, relevance to need, social
      acceptability, accessibility, efficiency and economy, and equity. Quantitative
      and qualitative methods were deployed and data were collected at three points in
      time over the evaluation period to provide a picture of change within each ward.
      The quantitative data gathered were mainly obtained through two self-report
      questionnaires that were developed specifically for the study. Both instruments
      were tested and found to have a high degree of internal consistency. The
      qualitative data gathered were collected using semistructured interviews.
      Analysis of the qualitative and quantitative data sets indicated that practice
      quality diminished rather than improved during the 6-month study period. Factors
      that emerged from the data as having influenced this outcome were: increases in
      ward team's overall workload, inadequate staffing levels and changes in
      expectations placed on those providing small group therapy. The findings are
      consistent with a national trend of deteriorating quality in in-patient care and
      point to some of the limitations of action learning as a practice development
      method. They also point to service factors that work against effective practice
      development.

PMID- 11966993
TI  - Nursing and extrapyramidal symptoms: a response to Clarke.

PMID- 11966994
TI  - Doubts and certainties in the nursing profession: a commentary.

PMID- 11966995
TI  - Not waving but drowning: a personal response to Barker and Grant.

PMID- 11966996
TI  - Doing what needs to be done: a respectful response to Burnard and Grant.

PMID- 11966997
TI  - The value of community mental health nurses based in primary care teams:
      'switching the light on in the cellar'.

PMID- 11967005
TI  - Conference report from the 7th World Congress of Biological Psychiatry (WCBP),
      Berlin, July, 2001.

PMID- 11967006
TI  - Methodological issues in studying the epidemiology of mild to moderate chronic
      renal insufficiency.
AB  - There is increasing interest in studying the epidemiology of subjects with mild
      to moderate chronic renal insufficiency (CRI), defined as reduced glomerular
      filtration rate (GFR) not requiring renal replacement therapy. This review
      discusses some of the methodological challenges presented by the epidemiological
      study of mild to moderate CRI that have not been adequately addressed in the
      literature. Issues that relate to defining the prevalence of CRI include between
      laboratory differences in serum creatinine (SCr) assays, within-person
      measurement errors in SCr, and differences in SCr in different demographic groups
      that are independent of GFR. Issues that relate to examining CRI as an outcome
      include the choice between a "slope" or "threshold" analysis. Issues that relate
      to examining CRI as an exposure include the choice of renal function measure (for
      example, SCr vs. estimated GFR) in multivariable analysis, whether to normalize
      renal function to body surface area or other body size parameters, potential
      effect modification of the association between CRI and the outcome and the
      complex relation between CRI, adverse outcomes, potential confounders and
      intermediary variables. As we enter an era of more intensive study of mild to
      moderate CRI, recognition of these potential pitfalls should guide researchers
      toward improving the quality of epidemiological research in this field.

PMID- 11967007
TI  - Gene expression profile of renal proximal tubules regulated by proteinuria.
AB  - BACKGROUND: Proximal tubules activated by reabsorption of protein are thought to
      play significant roles in the progression of kidney diseases. Thus,
      identification of genes related to proteinuria should provide insights into the
      pathological process of tubulointerstitial fibrosis. METHOD: Gene expression
      profiles were constructed by means of direct sequencing procedures to identify
      genes induced in the mouse kidney proximal tubules (PT) exposed to proteinuria.
      RESULTS: By comparing the gene expression of control PT to that of disease model
      PT, the abundantly expressed genes in control PT were down-regulated presumably
      because of potentially toxic effects of proteinuria. From the more than 1000 up
      regulated genes, an immunity related gene, thymic shared antigen-1 (TSA-1), and a
      novel gene, GS188, were selected for further characterization. The increased
      expression of TSA-1, a member of the Ly-6 family, and of GS188 in response to
      proteinuria was confirmed by Northern analysis, immunohistochemistry, in situ
      hybridization and laser microdissection along with real-time PCR analysis. Full
      length cloning of GS188 identified it as a family member of LR8 that was reported
      to express predominantly in fibroblasts. CONCLUSIONS: The gene expression
      profiles showed that the expression patterns in PT were changed dramatically by
      proteinuria. The profiles include novel genes that should be further
      characterized to aid the understanding of the pathophysiology of progressive
      kidney diseases.

PMID- 11967008
TI  - A complete mutation screen of the ADPKD genes by DHPLC.
AB  - BACKGROUND: Genetic analysis is a useful diagnostic tool in autosomal dominant
      polycystic kidney disease (ADPKD), especially when imaging results are equivocal.
      However, molecular diagnostics by direct mutation screening has proved difficult
      in this disorder due to genetic and allelic heterogeneity and complexity of the
      major locus, PKD1. METHODS: A protocol was developed to specifically amplify the
      exons of PKD1 and PKD2 from genomic DNA as 150 to 450 bp amplicons. These
      fragments were analyzed by the technique of denaturing high-performance liquid
      chromatography (DHPLC) using a Wave Fragment Analysis System (Transgenomics) to
      detect base-pair changes throughout both genes. DHPLC-detected changes were
      characterized by sequencing. RESULTS: Cost effective and sensitive mutation
      screening of the entire coding regions of PKD1 and PKD2 by DHPLC was optimized.
      All base-pair mutations to these genes that we previously characterized were
      detected as an altered DHPLC profile. To assess this method for routine
      diagnostic use, samples from a cohort of 45 genetically uncharacterized ADPKD
      patients were analyzed. Twenty-nine definite mutations were detected, 26 PKD1, 3
      PKD2 and a further five possible missense mutations were characterized leading to
      a maximal detection rate of 76%. A high level of polymorphism of PKD1 also was
      detected, with 71 different changes defined. The reproducibility of the DHPLC
      profile enabled the recognition of many common polymorphisms without the
      necessity for re-sequencing. CONCLUSIONS: DHPLC has been demonstrated to be an
      efficient and effective means for gene-based molecular diagnosis of ADPKD.
      Differentiating missense mutations and polymorphisms remains a challenge, but
      family-based segregation analysis is helpful.

PMID- 11967009
TI  - High protein-induced glomerular hypertrophy is vascular endothelial growth factor
      dependent.
AB  - BACKGROUND: Various growth factors and cytokines have been implicated in
      different forms of kidney enlargement such as renal growth following induction of
      diabetes, unilateral nephrectomy, and exposure to high protein diet. Vascular
      endothelial growth factor (VEGF) is essential for normal renal development and
      plays a role in diabetes-associated renal and glomerular enlargement. METHODS: To
      elucidate a possible role for VEGF in high protein-induced renal/glomerular
      enlargement, we examined the effect of a neutralizing VEGF-antibody (VEGF-ab) on
      kidney weight and glomerular volume in mice fed a high protein diet for up to
      seven days. RESULTS: At day 2 and day 7 of the experimental period, high protein
      diet induced a significant increase in the mean glomerular volume. This high
      protein-induced glomerular hypertrophy was completely prevented by treatment with
      VEGF-ab. Kidney weight was increased significantly only at day 7, and was not
      influenced by VEGF-ab treatment. High protein diet and/or VEGF-ab treatment had
      no effect on body weight, food intake, and liver or heart weight. CONCLUSIONS:
      The administration of a neutralizing VEGF-ab in mice fed a high protein diet for
      one week completely abolished the glomerular hypertrophy seen in placebo-treated
      animals on the same diet, without affecting kidney and body weight. These results
      demonstrate, to our knowledge for the first time, that high protein-induced
      glomerular hypertrophy is VEGF-dependent.

PMID- 11967010
TI  - Angiotensin II activation of the JAK/STAT pathway in mesangial cells is altered
      by high glucose.
AB  - BACKGROUND: Both high glucose (HG) and angiotensin II (Ang II) causes glomerular
      mesangial cell (GMC) growth and increased synthesis of matrix proteins like
      collagen IV contributing to diabetic nephropathy. We have recently found that
      exposure of vascular smooth muscle cells to HG augments the Ang II activation of
      the growth promoting JAK/STAT pathway. We hypothesized that Ang II activation of
      the JAK/STAT pathway is altered by HG in GMC, and that this pathway might be
      linked to the Ang II-induced growth and overproduction of collagen IV in GMC in
      HG conditions. METHODS: GMC were cultured under normal glucose (NG; 5.5 mmol/L)
      and HG (25 mmol/L) for 48 hours and stimulated with Ang II (0.1 micromol/L) for
      various times. GMC lysate was then immunoprecipitated and/or immunoblotted with
      SHP-1, SHP-2 and phosphospecific JAK2 and STAT antibodies. The HG and Ang II
      induced growth and collagen IV synthesis studies were performed in GMC
      transfected with JAK2 antisense or JAK2 sense. GMC growth was monitored via [3H]
      thymidine incorporation, and collagen IV synthesis via ELISA. RESULTS: We found
      that Ang II-induced JAK2, STAT1, STAT3, STAT5A/B and SHP-2 phosphorylations were
      enhanced by HG, whereas that of SHP-1 was reduced. Ang II-induced growth and
      collagen IV synthesis also were increased under HG conditions. Transfection of
      GMC with JAK2 antisense oligonucleotides blocked the Ang II-induced growth and
      collagen IV synthesis in both NG and HG conditions. CONCLUSION: These results
      provide evidence that activation of the JAK/STAT pathway by HG or/and Ang II may
      be of importance in the increased GMC cell growth and collagen IV synthesis that
      is seen in diabetic nephropathy.

PMID- 11967011
TI  - ATP release in human kidney cortex and its mitogenic effects in visceral
      glomerular epithelial cells.
AB  - BACKGROUND: In chronic renal failure the sympathetic nervous system is activated.
      Sympathetic cotransmitters released within the kidney may contribute to the
      progression of renal disease through receptor-mediated proliferative mechanisms.
      METHODS: In human renal cortex electrical stimulation induced adenosine 5'
      triphosphate (ATP; luciferin-luciferase-assay) and norepinephrine (HPLC) release
      was measured. ATP release also was induced by alpha1- and alpha2-adrenergic
      agonists. [3H]-thymidine uptake was tested in human visceral glomerular
      epithelial cells (vGEC) and mitogen-activated protein kinase (MAPK42/44)
      activation in vGEC and kidney cortex. The involved P2-receptors were
      characterized pharmacologically and by RT-PCR. RESULTS: Sympathetic nerve
      stimulation and alpha-adrenergic agonists induced release of ATP from human
      kidney cortex. Seventy-five percent of the ATP released originated from non
      neuronal sources, mainly through activation of alpha2-adrenergic receptors. ATP
      (1 to 100 micromol/L) and related nucleotides (1 to 100 micromol/L) increased
      [3H]-thymidine uptake. The adenine nucleotides ATP, ATPgammaS, ADP and ADPbetaS
      were about equally potent. UTP, UDP and alpha,beta-methylene ATP had no effect.
      ATP, ADPbetaS but not alpha,beta-methylene ATP activated MAPK42/44. ATP induced
      MAPK42/44 activation, and [3H]-thymidine uptake was abolished in the presence of
      the MAPK inhibitor PD 98059 (100 micromol/L). mRNA for P2X4,5,6,7 and
      P2Y1,2,4,6,11 were detected in human vGEC by RT-PCR. CONCLUSIONS: In human renal
      cortex, adrenergic stimulation releases ATP from neuronal and non-neuronal
      sources. ATP has mitogenic effects in vGEC and therefore the potential to
      contribute to progression in chronic renal disease. The pattern of purinoceptor
      agonist effects on DNA synthesis together with the mRNA expression suggests a
      major contribution of a P2Y1-like receptor.

PMID- 11967012
TI  - Mechanisms of the regulation of EGF receptor gene expression by calcitriol and
      parathyroid hormone in UMR 106-01 cells.
AB  - BACKGROUND: We have previously demonstrated that parathyroid hormone (PTH) and
      calcitriol increase the expression of epidermal growth factor receptors (EGFR) in
      UMR 106-01 osteoblast-like cells. The effect of PTH is mediated by cAMP and it
      involves an increase in the level of EGFR mRNA. The present studies were designed
      to investigate the mechanisms involved in the regulation of EGFR expression by
      PTH and calcitriol. METHODS: To examine the mechanism of the effect of calcitriol
      on EGFR expression, confluent cultures of UMR 106-01 cells were exposed to
      calcitriol and levels of EGFR mRNA were determined by reverse transcription
      polymerase chain reaction (RT-PCR). In order to study the effect of calcitriol on
      EGFR gene transcription, a candidate vitamin D-responsive element (VDRE) was
      identified in the EGFR gene promoter and complimentary 30-mer oligonucleotides
      spanning this region were tested for binding to recombinant VDR using EMSA.
      Transcriptional activity in response to calcitriol and PTH was tested in UMR 106
      01 cells stably transfected with a luciferase reporter construct containing the
      full length EGFR gene promoter. The effect of calcitriol on EGFR mRNA stability
      was examined in transcriptionally arrested cells. RESULTS: Treatment with
      calcitriol resulted in a time and dose dependent increase in EGFR mRNA levels in
      confluent cultures of UMR 106-01 osteoblast-like cells. Using EMSA, we
      demonstrated that the putative human EGFR VDRE binds to recombinant VDR in a
      retinoid X receptor (RXR)-dependent manner; however, calcitriol failed to
      increase transcriptional activity from a luciferase reporter construct containing
      the full-length EGFR gene promoter in stably transfected UMR 106-01 cells.
      Therefore, EGFR mRNA degradation was examined in transcriptionally arrested cells
      and calcitriol was found to prolong the half life of EGFR mRNA. Treatment of the
      cultures with PTH resulted in a ninefold increase in luciferase activity after
      four hours of exposure, a finding that was reproduced by treatment with
      forskolin. CONCLUSIONS: These studies demonstrate that the calciotropic hormones
      PTH and calcitriol increase EGF receptor expression by different mechanisms. The
      former increases EGFR gene transcription whereas the latter increases EGFR mRNA
      stability.

PMID- 11967013
TI  - Effect of combining ACE inhibitor and statin in severe experimental nephropathy.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor therapy given soon
      after disease induction uniformly prevents proteinuria in virtually all models of
      disease progression. This does not necessarily apply to patients with proteinuric
      nephropathies, who might be referred late in the course of their disease. Here we
      used a severe rat model of passive Heymann nephritis (PHN), which may mimic
      advanced phases of human membranous nephropathy, to study the response to ACE
      inhibitor alone or in combination with a HMG CoA reductase inhibitor (statin)
      that independently of the cholesterol-lowering effect influences pathways
      involved in inflammatory and fibrogenic processes. Therapies started when animals
      had massive proteinuria and renal lesions. METHODS: PHN was accelerated by
      uninephrectomy seven days after IV injection of rabbit anti-FX1A antibody. Four
      months later, when massive proteinuria and renal lesions were present, the rats
      were divided into five groups and daily given orally: vehicle; lisinopril 40
      mg/L; lisinopril 400 mg/L; simvastatin 2 mg/kg b.i.d; or lisinopril 40 mg/L plus
      simvastatin. Six normal rats served as controls. Animals were sacrificed at 10
      months. RESULTS: By the end of the study three PHN rats died in the vehicle
      group, four in the group given lisinopril at 40 mg/L and two in the group at 400
      mg/L, whereas all rats on simvastatin or combined therapy were alive. Blood
      pressure increased during time in PHN and was normalized by treatment with ACE
      inhibitor and combined therapy. Even at the high dose lisinopril failed to reduce
      proteinuria. Simvastatin only partially affected proteinuria. However, combining
      lisinopril with simvastatin had a remarkable antiproteinuric effect, such that at
      10 months the urinary proteins were comparable to pre-treatment values and
      significantly lower than either the vehicle or lisinopril groups.
      Hypercholesterolemia of PHN rats was limited by combined therapy, and a positive
      correlation was found between serum cholesterol and proteinuria. Renal function
      was only partially ameliorated by simvastatin but significantly improved by
      combined therapy. Drug combination significantly limited glomerulosclerosis,
      tubular damage and interstitial inflammation, compared to vehicle or drugs alone.
      Up-regulation of monocyte chemoattractant protein-1 (MCP-1) mRNA in PHN kidneys
      was not affected by lisinopril, it was inhibited by 30% after simvastatin, and
      almost completely normalized by lisinopril plus simvastatin. CONCLUSIONS: These
      data suggest that a combined ACE inhibitor and statin approach could represent a
      therapeutic option for patients with advanced renal disease in whom ACE
      inhibitors alone fail to lower proteinuria and injury to any substantial extent.

PMID- 11967014
TI  - Monitoring changes in gene expression in renal ischemia-reperfusion in the rat.
AB  - BACKGROUND: Although acute renal failure (ARF) is a relatively common disorder
      with major morbidity and mortality, its molecular basis remains incompletely
      defined. The present study examined global gene expression in the well
      characterized ischemia-reperfusion model of ARF using DNA microarray technology.
      METHODS: Male Wistar rats underwent bilateral renal ischemia (30 min) or sham
      operation, followed by reperfusion for 1, 2, 3 or 4 days. Plasma creatinine
      increased approximately fivefold over baseline, peaking on day 1. Renal total RNA
      was used to probe cDNA microarrays. RESULTS: Alterations in expression of 18
      genes were identified by microarray analysis. Nine genes were up-regulated
      (ADAM2, HO-1, UCP-2, and thymosin beta4 in the early phase and clusterin, vanin1,
      fibronectin, heat-responsive protein 12 and FK506 binding protein in the
      established phase), whereas another nine were down-regulated (glutamine
      synthetase, cytochrome p450 IId6, and cyp 2d9 in the early phase and cyp 4a14,
      Xist gene, PPARgamma, alpha-albumin, uromodulin, and ADH B2 in the established
      phase). The identities of these 18 genes were sequence-verified. Changes in gene
      expression of ADAM2, cyp2d6, fibronectin, HO-1 and PPARgamma were confirmed by
      quantitative real-time polymerase chain reaction (PCR). ADAM2, cyp2d6, and
      PPARgamma have not previously been known to be involved in ARF. CONCLUSION: Using
      DNA microarray technology, we identified changes in expression of 18 genes during
      renal ischemia-reperfusion injury in the rat. We confirmed changes in five genes
      (fibronectin, ADAM2, cyp 2d6, HO-1 and PPARgamma) by quantitative real-time PCR.
      Several genes, not previously been identified as playing a role in ischemic ARF,
      may have importance in this disease.

PMID- 11967015
TI  - Transferrin up-regulates chemokine synthesis by human proximal tubular epithelial
      cells: implication on mechanism of tubuloglomerular communication in
      glomerulopathic proteinura.
AB  - BACKGROUND: The pathogenesis of glomerulosclerosis and tubulointerstitial
      fibrosis in proteinuric renal disease is obscure. We recently showed that
      transferrin, a key proteinuric component, mediates proximal tubular epithelial
      cell (PTEC) C3 synthesis. To further examine whether proteinuric tubular injury
      may induce glomerular inflammation and to characterize the role of transferrin in
      activating PTEC, glomerular mesangial cells (MC) were exposed to transferrin
      activated PTEC culture supernatant and their proliferative and profibrotic
      responses analyzed. METHODS: Human PTEC and MC were obtained by primary culture.
      Confluent, transferrin-stimulated PTEC were grown in serum-free medium to produce
      a "conditioned" medium that was incubated with quiescent MC. The proliferative
      response of MC was then assessed by thymidine uptake, and the expression of
      fibrogenic factors measured by reverse transcription-polymerase chain reaction
      (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The chemokine profile in
      PTEC after transferrin treatment was examined by RT-PCR and ELISA. RESULTS:
      "Conditioned" supernatant from PTEC, which contained the highest amounts of
      platelet-derived growth factor (PDGF), stimulated MC proliferation compared with
      serum-free (P = 0.03) or transferrin-containing (P = 0.009) control media. This
      proliferative response was partially abrogated by treating MC with anti-PDGF. MC
      expression of PDGF, but not transforming growth factor-beta or intercellular cell
      adhesion molecule-1, was up-regulated by conditioned PTEC medium. Transferrin up
      regulated monocyte chemoattractant peptide-1, interleukin-8, and macrophage
      migration inhibitory factor expression in a time- and dose-dependent fashion, but
      had no effect on RANTES expression by PTEC. CONCLUSIONS: These results provide
      experimental evidence suggesting that there is a tubuloglomerular "cross-talk"
      mechanism in the proteinuric state. PTEC-secreted PDGF, which further induces
      mesangial PDGF, could partially account for the mesangial proliferation
      frequently observed in proteinuric renal disease. Transferrin is one of the
      culprit nephrotic proteins leading to tubular overexpression of various
      proinflammatory chemokines, which may explain the interstitial changes observed
      in proteinuric states.

PMID- 11967017
TI  - Altered cholesterol localization and caveolin expression during the evolution of
      acute renal failure.
AB  - BACKGROUND: Renal cortical/proximal tubule cholesterol accumulation, with
      preferential localization within plasma membrane "detergent resistant
      microdomains" (DRMs: rafts/caveolae), is a hallmark of the maintenance phase of
      acute renal failure (ARF). This study addressed two related issues: (1) Are
      maintenance-phase cholesterol increases accompanied by an up-regulation of
      caveolin, a DRM/caveolar-associated cholesterol binding protein? (2) Is DRM
      cholesterol/caveolin homeostasis acutely altered during the induction phase of
      ARF? METHODS: Mouse kidneys were subjected to ischemia +/- reperfusion (I/R)
      followed by assessment of cholesterol DRM partitioning. Acute cell injury effects
      on potential caveolin release from isolated proximal tubules or into urine also
      were assessed. Finally, renal cortical/isolated proximal tubule caveolin levels
      were determined 18 hours after I/R or myoglobinuric ARF. RESULTS: Acute ischemia
      causes a rapid shift of cholesterol into cortical DRMs (>22%). Cholesterol
      migration into DRMs also was observed in ATP-depleted cultured proximal tubule
      (HK-2) cells. Acute hypoxic or toxic tubule injury induced plasma membrane
      caveolin release (Western blot). By the maintenance phase of ARF, marked renal
      cortical/proximal tubule caveolin increases resulted. CONCLUSIONS: Acute proximal
      tubular injury damages caveolar/DRM structures, as determined by cholesterol
      maldistribution and caveolin release. Post-injury, there is a dramatic up
      regulation of renal cortical/proximal tubule caveolin, suggesting an increased
      caveolar mass. These findings indicate, to our knowledge for the first time, that
      dysregulation of caveolae/raft microdomain expression is a correlate of, and
      potential participant in, the induction and maintenance phases of ischemic and
      toxic forms of experimental ARF.

PMID- 11967016
TI  - Human antiglomerular basement membrane autoantibody disease in XenoMouse II.
AB  - BACKGROUND: Previous studies have identified regions within alpha3(IV) collagen
      in human antiglomerular basement membrane (anti-GBM) disease, however,
      information pertaining to the nature of the pathogenic human autoantibodies has
      been limited by a lack of a relevant disease model. Availability of engineered
      mice that produce antibodies (that is, XenoMouse II strains) provides an ideal
      opportunity to examine the human antibody response. METHODS: XenoMouse II mice
      that produce human IgG2 (gamma2kappa) in response to antigenic challenge were
      immunized with various forms of alpha3(IV)NC1 GBM collagen, including native
      bovine alpha3(IV) NCl collagen, E. coli expressed r alpha3(IV)NCl, and mammalian
      fetal kidney 293 cell expressed r alpha3(IV)NC1 preparations. The mice were
      evaluated for autoantibody (Ab) production and nephritis. RESULTS: All immunized
      XenoMouse II animals produced human anti-GBM Ab associated with proliferative
      glomerulonephritis, linear IgG deposits along the murine GBM and tubular basement
      membrane (TBM), C3 deposits (weaker). A fully human mAb (Ig gamma2kappa),
      produced from a mouse immunized with native bovine alpha3(IV)NCl collagen
      produced basement membrane deposits, nephritis and proteinuria on transfer to
      normal XenoMouse II. Furthermore, monoclonal antibodies (mAb) shared idiotypic
      properties with polyclonal autoantibodies derived from patients with anti-GBM
      disease, supporting a structural relationship among the antibodies. CONCLUSIONS:
      The results further support the importance of alpha3(IV)NCl collagen in the
      pathogenesis of anti-GBM disease. Moreover, to our knowledge this is the first
      demonstration that experimentally induced, pathogenic human autoantibodies result
      in disease. This new model of anti-GBM disease, therefore, provides the means and
      unique reagents to both decipher the molecular basis of the human anti-GBM
      autoantibody response and the opportunity to test specific therapies aimed at
      modulation of either B cells producing human autoantibodies or the human
      pathogenic antibodies themselves, in vivo, prior to trial in patients with the
      spontaneous form of the disease.

PMID- 11967018
TI  - Y-27632 prevents tubulointerstitial fibrosis in mouse kidneys with unilateral
      ureteral obstruction.
AB  - BACKGROUND: The small GTPase Rho is involved in cell-to-substratum adhesion and
      cell contraction. These actions of Rho mediated by downstream Rho effectors such
      as Rho-associated coiled-coil forming protein kinase (ROCK) may be partly
      responsible for the progression of renal interstitial fibrosis. METHODS: The anti
      fibrosis effects of Y-27632, a specific ROCK inhibitor, were studied both in vivo
      (unilateral ureteral obstruction; UUO) and in vitro. To investigate the
      therapeutic efficacy of Y-27632 in UUO kidneys, smooth muscle alpha actin
      (SMalphaA) expression, macrophage infiltration and fibrosis in the obstructed
      kidneys were studied. SMalphaA, transforming growth factor beta (TGF-beta),
      alpha1 (I) collagen, osteopontin, macrophage chemoattractant peptide-1 (MCP-1),
      and intercellular adhesion molecule-1 (ICAM-1) gene expression were examined by
      Northern blotting. To elucidate the mechanism linking the Rho-ROCK pathway with
      renal fibrosis, the effects of Y-27632 on in vitro cell proliferation and cell
      migration were studied. RESULTS: In vivo analysis showed that Y-27632 suppressed
      SMalphaA expression, macrophage infiltration and interstitial fibrosis, and that
      Y-27632 suppressed SMalphaA, TGF-beta and alpha1 (I) collagen mRNA expression. In
      vitro analysis showed that Y-27632 did not suppress proliferation of renal
      fibroblasts but suppressed migration of macrophages. CONCLUSIONS: The Rho-ROCK
      system may play an important role in the development of tissue fibrosis, and the
      Rho-ROCK signaling pathway may be a new therapeutic target for preventing
      interstitial fibrosis in progressive renal disease.

PMID- 11967019
TI  - Renal ischemia-reperfusion increases endothelial VEGFR-2 without increasing VEGF
      or VEGFR-1 expression.
AB  - BACKGROUND: Hypoxia is a potent stimulus to angiogenesis. Expression of the
      angiogenic growth factor vascular endothelial growth factor (VEGF) and its
      receptors (VEGFR-1 and VEGFR-2) is up-regulated by hypoxia in a variety of organs
      and cell lines. We have previously reported that VEGF expression is not increased
      in renal ischemia-reperfusion injury, although tubular cells concentrate VEGF at
      their basolateral surface. In this study we assess whether altered VEGF receptor
      expression compensates for the lack of VEGF regulation during renal ischemia
      reperfusion injury. METHODS: VEGFR-1 mRNA expression was assessed by Northern
      blotting and semiquantitative reverse transcription-polymerase chain reaction (RT
      PCR). VEGFR-2 mRNA expression was analyzed by Northern blotting and in situ
      hybridization (ISH), while VEGFR-2 protein expression was studied using
      immunohistochemistry. VEGF mRNA expression was assessed by ISH. RESULTS: VEGFR-2
      mRNA and protein expression were up-regulated without an increase in VEGF or
      VEGFR-1 expression. Normal kidneys showed low-level VEGFR-2 mRNA and protein
      expression in glomerular and peritubular endothelium. Following ischemia and
      ischemia-reperfusion, a marked increase in VEGFR-2 mRNA and protein expression
      was seen (2- to 4-fold). Most prominent was VEGFR-2 mRNA up-regulation in the
      glomerulus although, surprisingly, increased protein was not demonstrated here.
      ISH showed that VEGF mRNA was not up-regulated in this model, confirming our
      previous findings for VEGF. CONCLUSION: VEGF and VEGFR-1 expression are not
      increased by renal ischemia and ischemia-reperfusion injury. Instead, endothelial
      expression of VEGFR-2 is increased. VEGFR-2 up-regulation in renal ischemia
      reperfusion may be important in mediating the mitogenic and anti-apoptotic
      actions of VEGF on endothelial cells, thereby preserving the integrity of the
      endothelium and the potential for blood supply to ischemic tissues.

PMID- 11967020
TI  - Nitric oxide increases adrenomedullin receptor function in rat mesangial cells.
AB  - BACKGROUND: Adrenomedullin (ADM) exerts antiproliferative effects on rat
      mesangial cells in vitro and, therefore is a possible renoprotective agent. In
      contrast, nitric oxide (NO) is capable of exerting both cytoprotective and
      cytotoxic actions. It was the objective of the present study to examine whether
      NO stimulates the ADM system. METHODS: Rat mesangial cells were incubated with
      the NO donors GSNO and SNAP, the guanylate cyclase inhibitor ODQ, and the cGMP
      analog 8-bromo-cGMP. ADM radioligand binding, ADM-induced intracellular cAMP
      accumulation (radioimmunoassay) and ADM receptor gene expression (TaqMan real
      time PCR) were measured. RESULTS: Twenty-four hour treatment of mesangial cells
      with GSNO and SNAP (100 micromol/L each) increased the maximal binding of ADM to
      its receptor from 52%+/- 4% to 101%+/- 4% (P < 0.001) and 81%+/- 2% (P < 0.001),
      respectively. GSNO, SNAP (both 100 micromol/L) and 8-bromo-cGMP (50 micromol/L)
      increased EC50 from 9.9 x 10-8 to 7.0 x 10-10, 4.8 x 10-10, 1.1 x 10-9,
      respectively. In contrast, combined pretreatment with GSNO (100 micromol/L) and
      ODQ (100 micromol/L) reduced EC50 to values similar to the control cells (2.4 x
      10-8). In contrast, ADM receptor gene expression was reduced significantly by
      different concentrations of GSNO, SNAP, and by 50 micromol/L 8-bromo-cGMP, but
      not by 8-bromo-cAMP. CONCLUSIONS: NO increases ADM signal transduction via a cGMP
      dependent pathway. This effect is caused, at least in part, by an increase in ADM
      receptor availability and is counteracted in a feedback manner on the mRNA level.
      This mechanism might direct the impact of NO on mesangial cell function toward
      cytoprotection.

PMID- 11967021
TI  - Role of basic fibroblast growth factor-2 in epithelial-mesenchymal
      transformation.
AB  - BACKGROUND: Epithelial-mesenchymal transformation (EMT) plays an important role
      in embryonic development and tumorigenesis and has been described in organ
      remodeling during fibrogenesis. In the kidney, EMT can be induced efficiently in
      cultured proximal tubular epithelium by coincubation of transforming growth
      factor (TGF)-beta1 and epidermal growth factor (EGF). Recently, we also have
      observed overexpression of basic fibroblast growth factor-2 (FGF-2) protein and
      mRNA in human kidneys with marked interstitial fibrosis. The aims of the present
      study were to compare the effects of FGF-2 as a facilitator of EMT in tubular
      epithelial cells with EGF and TGF-beta1. We analyzed the morphogenic effects of
      the three cytokines on four different aspects of EMT: cell motility, expression
      and regulation of cellular markers, synthesis and secretion of extracellular
      matrix (ECM) proteins as well as matrix degradation. METHODS: Cell motility was
      studied by a migration assay and cell differentiation markers were analyzed by
      immunofluorescence and immunoblots. In addition, regulation of the epithelial
      adhesion molecule E-cadherin and fibroblast-specific protein 1 (FSP1) were
      analyzed by luciferase reporter constructs and stable transfections. ELISAs for
      collagen types I and IV and fibronectin were used for ECM synthesis, and
      zymograms were utilized for analysis of matrix degradation. RESULTS: FGF-2
      induced cell motility across a tubular basement membrane in two tubular cell
      lines. All three cytokines induced the expression of vimentin and FSP1, but only
      FGF-2 and TGF-beta1 reduced cytokeratin expression by immunofluorescence. These
      effects were most demonstrable in the distal tubular epithelial cell line and
      were confirmed by immunoblot analyses. Expression of E-cadherin was reduced by
      61.5 +/- 3.3% and expression of cytokeratin by 91 +/- 0.5% by TGF-beta1 plus FGF
      2. Conversely, the mesenchymal markers alpha-smooth muscle actin (SMA) and FSP1
      were induced with FGF-2 by 2.2 +/- 0.1-fold and 6.8 +/- 0.9-fold, respectively.
      Interestingly, de novo expression of the mesenchymal marker OB-cadherin was
      induced only by FGF-2 and EGF but not by TGF-beta1. All three cytokines
      stimulated FSP1 and decreased E-cadherin promoter activity. FGF-2 also induced
      intracellular fibronectin synthesis but not secretion, the latter of which was
      stimulated exclusively by TGF-beta1. Finally, zymographic analyses demonstrated
      that FGF-2 induced MMP-2 activity by 2.6 +/- 0.5-fold and MMP-9 activity by 2.4
      +/- 0.1-fold, providing a mechanism for basement membrane disintegration and
      migratory access of transforming epithelium to the interstitium. CONCLUSIONS: FGF
      2 makes an important contribution to the mechanisms of EMT by stimulating
      microenvironmental proteases essential for disaggregation of organ-based
      epithelial units. Furthermore, the expression of epithelial and mesenchymal
      marker proteins seems to be affected at the promoter level.

PMID- 11967022
TI  - Hyaluronan increases glomerular cyclooxygenase-2 protein expression in a p38 MAP
      kinase-dependent process.
AB  - BACKGROUND: Accumulation of the matrix glycosaminoglycan hyaluronan occurs in
      many types of renal injury but could follow any provision of hyaluronan substrate
      to the kidney, for example, through widespread use of supplementary glucosamine
      in osteoarthritic conditions. Hyaluronan can increase cyclooxygenase-2 (COX-2)
      protein and prostaglandin production. This effect was characterized in rat renal
      glomeruli to determine the cellular mechanism of activation. METHODS: Isolated
      glomeruli were treated with purified hyaluronan (molecular mass 2 x 105 D) for up
      to 24 hours. RESULTS: An increase in cyclooxygenase capacity and COX-2 protein
      was shown to follow the activation of p38-mitogen-activated protein (MAP) kinase
      and to be inhibited by a specific pyridinyl imadazole inhibitor (SB 202190).
      Hyaluronan-induced activation of cytosolic phospholipase A2 also was shown to be
      a p38 MAP kinase effect in these preparations. Prostaglandin production was
      inhibited by COX-2-specific non-steroidal anti-inflammatory compounds (NS-398 and
      celecoxib) but, as shown for many non-steroidal anti-inflammatory drugs (NSAIDs),
      an increase in COX-2 protein accompanied this inhibition. CONCLUSIONS: We propose
      that these findings have clinical relevance. Prostaglandins have a number of
      important intrarenal regulatory effects leading to some debate over renal
      function with the use of NSAIDs. Where hyaluronan is increased, p38 MAP-kinase
      dependent provision of prostaglandin substrate, via activation of cytosolic
      phospholipase A2, and a concomitant increase in cyclooxygenase-2 protein would
      raise renal prostaglandin levels. While NSAID treatment can prevent a rise in
      prostaglandin levels, it needs to be maintained to avoid possible exacerbation of
      pro-inflammatory conditions due to increased COX-2 protein levels.

PMID- 11967023
TI  - Putative subunits of the rat mesangial KATP: a type 2B sulfonylurea receptor and
      an inwardly rectifying K+ channel.
AB  - BACKGROUND: Sulfonylurea agents exert their physiological effects in many cell
      types via binding to specific sulfonylurea receptors (SUR). SUR couple to
      inwardly-rectifying K+ channel (Kir6.x) to form tetradimeric ATP-sensitive K+
      channels (KATP). The SUR subunits confer ATP-sensitivity on KATP and also provide
      the binding sites for sulfonylureas and other pharmacological agents. Our
      previous work demonstrated that the exposure of mesangial cells (MC) to
      sulfonylureas generated profound effects on MC glucose uptake and matrix
      metabolism and induced heightened cell contractility in association with Ca2+
      transients. Because these responses likely resulted from the binding of
      sulfonylurea to a mesangial SUR2, we subsequently documented [3H]-glibenclamide
      binding to MC and the gene expression of several mesangial SUR2 transcripts. From
      these data, we inferred that MC expressed the components of a mesangial KATP and
      sought to establish their presence in primary MC. METHODS: To obtain mesangial
      SUR2 cDNA sequences, rapid amplification of cDNA ends (RACE) was utilized. DNA
      sequences were established by the fluorescent dye termination method. Gene
      expression of mesangial SUR2 and Kir6.1/2 was examined by reverse transcription
      polymerase chain reaction (RT-PCR) and Northern analysis. SUR2 proteins were
      identified by immunoblotting of mesangial proteins from membrane-enriched
      fractions with polyclonal antiserum directed against SUR2. RESULTS: RACE cloning
      yielded two mesangial SUR2 cDNAs of 4.8 and 6.7 kbp whose open reading frames
      translated proteins of 964 and 1535 aa, respectively. Using probes specific to
      each cDNA, the presence of a unique, 5.5 kbp serum-regulated mesangial SUR2
      splice variant was established. The sequence of this mesangial SUR2 (mcSUR2B)
      shares identity with the recently cloned rat SUR2B (rSUR2B), but, in comparison
      to rSUR2B, is truncated by 12 exons at the N-terminus where it contains a unique
      insert of 16 aa. Immunoblotting studies with anti-SUR2 antiserum demonstrated
      SUR2 proteins of 108 and 170 kD in membrane-enriched fractions of MC protein
      extracts. Complementary studies showed abundant gene expression of Kir6.1,
      thereby establishing gene expression of both components of KATP. CONCLUSIONS:
      Based upon analogy to vascular smooth muscle cells (VSMC), there are at least two
      putative mesangial KATP that most likely represent hetero-octamers, comprised of
      either rSUR2B or mcSUR2 in complex with Kir6.1. Our results define the mesangial
      SUR2B as the possible first link in a chain of cellular events that culminates in
      MC contraction and altered extracellular matrix metabolism following exposure to
      sulfonylureas. In addition, our results serve as the basis for the future
      elucidation of the electrophysiologic characteristics of the mesangial KATP and
      the study of endogenous regulators of mesangial cell contractility.

PMID- 11967024
TI  - Chronic taurine treatment ameliorates reduction in saline-induced diuresis and
      natriuresis.
AB  - BACKGROUND: Taurine is an osmolyte found in high concentration in the kidney.
      Both the modulation of tissue taurine stores and the exogenous administration of
      taurine are known to affect renal function. Therefore, it is likely that taurine
      therapy could benefit the dysfunctional kidney. METHODS: To test this idea, the
      present study examined the effect of chronic taurine administration on the
      excretory responses to acute saline volume loading by the unilaterally
      nephrectomized (UNX) control and the UNX glucose-intolerant rat (ages 3 to 9
      months). RESULTS: Sham-operated animals excreted similar amounts of the
      administered fluid and sodium loads with age. However, unilateral nephrectomy was
      associated with a significant reduction in the response to saline volume loading.
      This defect was prominent at a younger age (that is, 3 months) in the UNX glucose
      intolerant than the UNX control (6 months old) rat. Chronic taurine treatment
      ameliorated the reduction in saline-induced diuresis and natriuresis by both the
      UNX control and the UNX glucose intolerant rat. Both an increase in glomerular
      filtration and a reduction in tubular reabsorption of fluid and sodium caused
      this taurine-mediated improvement in renal excretory function. CONCLUSION:
      Taurine treatment protects the kidney of the UNX rat against an age-dependent
      decline in excretory efficiency.

PMID- 11967025
TI  - Major role of organic anion transporter 3 in the transport of indoxyl sulfate in
      the kidney.
AB  - BACKGROUND: Indoxyl sulfate is a uremic toxin that accumulates in the body
      because of the patient's inability to excrete it and it induces a number of
      uremic symptoms and leads to chronic renal failure. The functional failure of the
      excretion system for indoxyl sulfate causes its accumulation in blood. The
      purpose of the present study was to characterize the transport mechanism
      responsible for the renal excretion of indoxyl sulfate. METHODS: The [3H]indoxyl
      sulfate transport mechanism was investigated using an in vivo tissue-sampling
      single-injection technique, the kidney uptake index (KUI) method. Rat organic
      anion transporter 3 (rOAT3)-expressing Xenopus laevis oocyte system was used for
      measuring [3H]indoxyl sulfate uptake activity. RESULTS: Probenecid showed a
      concentration-dependent inhibitory effect on the uptake of [3H]indoxyl sulfate
      using the KUI method, and uptake was inhibited by organic anions such as para
      aminohippuric acid (PAH) and benzylpenicillin, by weak base such as cimetidine,
      and by uremic toxins, such as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid
      (CMPF) and hippuric acid (HA). However, salicylic acid, indomethacin, 3,5,3'
      triiodo-l-thyronine and indole acetic acid (IA) had no effect on the uptake.
      rOAT3-expressing oocytes exhibited uptake of [3H]indoxyl sulfate by rOAT3 (Km =
      158 micromol/L). Moreover, a number of uremic toxins inhibited the uptake of
      [3H]indoxyl sulfate by rOAT3. CONCLUSIONS: These results suggest that rOAT3 is
      responsible for the renal uptake of indoxyl sulfate, and uremic toxins share the
      transport mechanism for indoxyl sulfate. Mutual inhibition of these uremic toxins
      via OAT3 may accelerate their accumulation in the body and, thereby, the
      progression of nephrotoxicity in uremia.

PMID- 11967026
TI  - Up-regulation of acyl-coenzyme A:cholesterol acyltransferase (ACAT) in nephrotic
      syndrome.
AB  - BACKGROUND: We have previously demonstrated that hypercholesterolemia in rats
      with puromycin-induced nephrotic syndrome (NS) is associated with up-regulation
      of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and relative
      down-regulation of cholesterol 7alpha-hydroxylase (Ch-7alpha), which represent
      the rate-limiting steps in cholesterol biosynthesis and catabolism. Expression of
      HMG-CoA reductase is inhibited and Ch-7alpha is augmented by intracellular free
      cholesterol, which is avidly esterified by acyl-CoA:cholesterol acyltransferase
      (ACAT). Therefore, we hypothesized that NS may result in up-regulation of hepatic
      ACAT. METHODS: Hepatic tissue ACAT mRNA (Northern blot), protein (Western blot)
      and enzymatic activity were determined in rats with puromycin-induced NS, placebo
      treated control rats and Nagase hypoalbuminemic (NAG) rats. RESULTS: The NS group
      exhibited heavy proteinuria, hypoalbuminemia, normal creatinine clearance, severe
      hypercholesterolemia and hypertriglyceridemia. Despite severe hypoalbuminemia,
      NAG rats with inherited hypoalbuminemia exhibited only a mild elevation of plasma
      cholesterol and triglycerides. Severe hypercholesterolemia in the NS group was
      coupled with depressed liver tissue free cholesterol concentration and marked
      increases in hepatic ACAT mRNA, protein and enzymatic activity. In contrast, ACAT
      mRNA and protein contents of the liver were normal and ACAT activity was mildly
      elevated in the NAG group. CONCLUSIONS: NS results in marked up-regulation of
      hepatic ACAT, which is primarily due to proteinuria and not hypoalbuminemia,
      since the latter alone, as seen in NAG rats, does not significantly impact ACAT
      expression. Elevated ACAT in NS can contribute to dysregulation of cholesterol
      biosynthesis and catabolism by limiting the normal cholesterol signaling involved
      in regulation of these processes.

PMID- 11967027
TI  - Proteinuria is preceded by decreased nitric oxide synthesis and prevented by a NO
      donor in cholesterol-fed rats.
AB  - BACKGROUND: Hypercholesterolemia decreases nitric oxide (NO) availability in the
      circulation and induces podocyte activation and renal injury in rats. It is
      unknown whether hypercholesterolemia decreases renal NO availability. To
      dissociate the injury-independent effect of hypercholesterolemia on renal NO
      availability from secondary effects of proteinuria, increasing concentrations of
      cholesterol were administered. To determine whether podocyte activation and renal
      injury were associated with NO deficiency, molsidomine, an exogenous NO donor,
      was administered to hypercholesterolemic rats. METHODS: Female rats were fed 0,
      0.5, 1, or 2% cholesterol for 24 weeks. Rats fed 2% cholesterol were also studied
      for two weeks. In addition rats fed 0 or 1% cholesterol received 120 mg
      molsidomine/L drinking water. Renal NO availability was determined by measuring
      renal NO synthesis and superoxide activity. Podocyte activation was monitored by
      desmin staining. RESULTS: Hypercholesterolemia dose-dependently increased
      proteinuria. In the absence of proteinuria, hypercholesterolemia decreased renal
      NO synthesis (4.2 +/- 0.5 in 0.5% cholesterol vs. 6.8 +/- 0.6 pmol/min/mg protein
      in controls; P < 0.05). With the exception of neuronal nitric oxide synthase
      (nNOS), renal NOS protein mass remained unaffected. Renal superoxide activity was
      dose-dependently increased, thus further lowering renal NO availability. Podocyte
      injury was dose-dependently increased even in the absence of proteinuria (score,
      40 +/- 4 in 0.5% cholesterol vs. 9 +/- 4 in controls; P < 0.05). After two weeks,
      hypercholesterolemia caused no proteinuria, but did cause some podocyte injury.
      Renal NOS activity was decreased, but glomerular endothelial NOS (eNOS) staining
      was unchanged. Molsidomine prevented proteinuria, podocyte activation, and all
      further renal injury. CONCLUSIONS: Hypercholesterolemia decreases renal NO
      synthesis, and induces podocyte activation before proteinuria appears. Renal
      superoxide activity is increased once rats are proteinuric, further lowering
      renal NO availability. All of these changes can be prevented by a NO donor.

PMID- 11967028
TI  - Renal hemodynamic effects of somatostatin are not related to inhibition of
      endogenous insulin release.
AB  - BACKGROUND: Somatostatin inhibits endocrine and exocrine secretions and exerts
      renal vasoconstriction. The mechanism underlying somatostatin's vascular effects
      is unknown. Since insulin can cause vasodilation, we hypothesized that removal of
      basal insulin release by somatostatin may contribute to somatostatin-induced
      renal vasoconstriction. METHODS: The study was conducted in different protocols
      comprising forty-six healthy male volunteers. Randomized studies were performed
      to compare the effects of somatostatin alone (0.1 microg/kg/min) to the effects
      of somatostatin + low dose insulin (0.1 mU/kg/min), the effects of somatostatin +
      low dose insulin to the effects of somatostatin + high dose insulin (1.5
      mU/kg/min), and the effects of insulin (1.5 mU/kg/min) + somatostatin. Renal
      plasma flow (RPF) and glomerular filtration rate (GFR) were measured with the
      para-aminohippurate (PAH) and the inulin clearance technique, respectively. Blood
      pressure and pulse rate were measured non-invasively. RESULTS: Somatostatin alone
      decreased GFR (-14 +/- 6%, P < 0.001) and RPF (-16 +/- 7%, P < 0.001) whereas
      systemic hemodynamics were unchanged. Preceding or concomitant infusion of
      insulin at high doses (insulin plasma concentration of 127 +/- 25 or 144 +/- 17
      microU/mL) but not co-infusion with low dose insulin (insulin plasma
      concentration of 11 +/- 3 microU/mL) mitigated or reversed the vasoconstrictive
      actions of somatostatin on GFR and RPF. CONCLUSIONS: Somatostatin induces marked
      renal vasoconstriction and exogenous restoration of fasting insulin
      concentrations does not influence the renal vascular effects. Therefore, it is
      unlikely that somatostatin-induced vasoconstriction is due to removal of basal
      insulin. Plasma insulin concentrations in the high postprandial range can reverse
      somatostatin-induced renal vasoconstriction, suggesting functional antagonism.

PMID- 11967029
TI  - Increased genetic susceptibility to renal damage in the stroke-prone
      spontaneously hypertensive rat.
AB  - BACKGROUND: The spontaneously hypertensive rat (SHR) develops much less renal
      damage than the stroke-prone strain of SHR (SHRsp) after salt-supplementation,
      and it has been proposed that these strains differ in their genetic
      susceptibility to renal damage. However, radiotelemetric BP measurements have
      shown that salt-supplementation results in more severe and accelerated
      hypertension in the SHRsp. Therefore, it is unclear whether the differences in
      renal damage are due to differences in BP exposure or true differences in
      intrinsic (genetic) renal susceptibility to hypertensive damage. METHODS: Kidney
      cross transplantation was performed between the SHR and SHRsp strains in
      uninephrectomized recipients to allow an investigation of the susceptibility to
      renal damage in SHR and SHRsp kidneys maintained in the same host and exposed to
      the same BP profile and metabolic environment. Following transplantation, BP was
      radiotelemetrically monitored before and after an 8% NaCl diet given to
      accelerate hypertension and renal damage. Then the kidneys were removed and renal
      damage was assessed histologically. RESULTS: In the SHR recipients, the SHRsp
      donor kidneys exhibited more hypertensive damage than the contralateral native
      SHR kidneys, but histologic evidence of mild cellular immunologic rejection also
      was observed that could have facilitated the increased renal damage. However,
      even in SHRsp recipients, the native SHRsp kidneys exhibited twice the damage
      seen in the contralateral transplanted SHR kidneys. CONCLUSION: These data
      unequivocally demonstrate that the SHRsp kidneys are intrinsically more
      susceptible than the SHR kidneys to renal damage when exposed to exactly the same
      BP and metabolic environment.

PMID- 11967031
TI  - Kidney cancer in the Swedish Family Cancer Database: familial risks and second
      primary malignancies.
AB  - BACKGROUND: Familial risks in kidney cancer and association with second primary
      malignancies were studied using the nationwide Swedish Family Cancer Database.
      METHODS: Cancer data were retrieved from the Swedish Cancer Registry from years
      1961 to 1998 and included 23,137 cases of kidney cancer. Standardized incidence
      ratios (SIRs) were used to measure the cancer risks. RESULTS: Seventy-one
      families were identified where both a parent and an offspring had kidney cancer,
      giving a familial risk for offspring of 1.56 (1.22 to 1.95) and population
      attributable proportion of 0.78%. A risk for kidney cancer from an affected
      sibling was considerably higher with a SIR of 4.72 (2.28 to 9.20), giving an
      attributable proportion of 0.77%. The discordant tumor site that was associated
      with kidney cancer between two generations was hemangioblastoma of central
      nervous system. Discordant cancer sites that were associated with kidney cancer
      in siblings were ovaries, endocrine glands and pancreas. There was an over
      threefold increase of second primary malignancies of the urinary bladder, nervous
      system and endocrine gland in kidney cancer patients. The risks for second
      primary hemangioblastoma following kidney cancer or familial kidney cancer was
      21.19 (6.69 to 43.83) and 1206 (114 to 3456), respectively. CONCLUSIONS: The high
      ratio of sibling risk to offspring risk in kidney cancer may reflect a recessive
      susceptibility. The high risk for second primary cancers in the patients without
      family history is consistent with a polygenic model and variable degree of
      environmental modification.

PMID- 11967030
TI  - Risk factors for cyclosporine-induced tubulointerstitial lesions in children with
      minimal change nephrotic syndrome.
AB  - BACKGROUND: Cyclosporine (CsA) is effective for the treatment of children with
      steroid-dependent and -resistant nephrotic syndrome (NS), but it can result in
      chronic CsA nephrotoxicity including CsA-induced tubulointerstitial lesions. The
      factors responsible for the development of CsA-induced tubulointerstitial lesions
      are unknown. METHODS: To identify the risk factors for the development of CsA
      induced tubulointerstitial lesions in children with minimal change NS who had
      been treated with long-term moderate-dose CsA, we compared several clinical and
      laboratory factors of 37 patients with and without CsA-induced tubulointerstitial
      lesions by the Mann-Whitney U test, Fisher's exact test, and stepwise logistic
      regression analysis. RESULTS: Thirteen patients had CsA-induced
      tubulointerstitial lesions and 24 patients had none. Among clinical and
      laboratory factors, the duration of CsA treatment (P = 0.003) and the duration of
      heavy proteinuria during CsA treatment (P = 0.024) were related to the
      development of CsA-induced tubulointerstitial lesions as determined by the
      univariate analyses. Indeed, CsA-induced tubulointerstitial lesions were found in
      2 of 18 (11%) patients who had been treated with CsA for less than 24 months, but
      in 11 of 19 patients (58%) who had been treated for more than 24 months (P =
      0.005). They were also found in 4 of 23 patients (17%) who had heavy proteinuria
      for less than 30 days during CsA treatment, but in 9 of 14 patients (64%) who had
      heavy proteinuria for more than 30 days (P = 0.006). Stepwise logistic-regression
      analysis revealed that the duration of CsA treatment for more than 24 months
      (chi2 = 6.203, P = 0.013) and the duration of heavy proteinuria during CsA
      treatment for more than 30 days (chi2 = 5.871, P = 0.015) were independent risk
      factors for the development of CsA-induced tubulointerstitial lesions.
      CONCLUSIONS: Duration of the CsA treatment and the duration of heavy proteinuria
      during CsA treatment were independent significant risk factors for the
      development of CsA-induced tubulointerstitial lesions in children with MCNS who
      had been treated with long-term moderate-dose CsA.

PMID- 11967032
TI  - Bone mineral density is not diminished by mild to moderate chronic renal
      insufficiency.
AB  - BACKGROUND: Persons with end-stage renal disease are at higher risk for
      osteopenia and hip fracture relative to the age-matched general population.
      Persons with mild to moderate chronic renal insufficiency (CRI) may have reduced
      bone mineral density (BMD) as a result of abnormalities in acid-base and vitamin
      D-parathyroid hormone homeostasis. METHODS: We analyzed data on 13,848 adults
      aged 20 and above from the Third National Health and Nutrition Examination Survey
      (NHANES III; 1988-1994). Regression models were used to determine the
      relationship between femoral BMD and renal function, the latter assessed using
      serum creatinine, blood urea nitrogen or Cockcroft-Gault creatinine clearance. To
      control for confounding, we fit sex-stratified models that adjusted for age,
      weight, height, race-ethnicity, menopausal status, estrogen use, activity level,
      family history of osteoporosis, diuretic use, and dietary intake of calcium and
      alcohol. RESULTS: Although subjects with reduced renal function had significantly
      lower femoral BMD in unadjusted analysis, the association between CRI and bone
      mineral density was extinguished after adjustment in the multivariate models. In
      fact, controlling for only sex, age and weight was sufficient to extinguish any
      negative association between decreased renal function and decreased bone mineral
      density. CONCLUSION: Although subjects with worse renal function have
      significantly lower femoral BMD, this association can be explained by
      confounding, principally by sex, age and weight. After taking into account the
      facts that women, older individuals and smaller individuals have less renal
      function and lower BMD, renal function itself is not independently associated
      with BMD.

PMID- 11967033
TI  - Reduced crystallization inhibition by urine from women with nephrolithiasis.
AB  - BACKGROUND: Human urine is known to inhibit growth, aggregation, nucleation, and
      cell adhesion of calcium oxalate monohydrate (COM) crystals, the main solid phase
      of human kidney stones. This study tested the hypothesis that low levels of
      inhibition are present in women with calcium oxalate stones and, therefore, could
      promote stone production. METHODS: In 17 stone-forming women and 17 normal women
      matched in age within five years, inhibition by dialyzed urine proteins of COM
      growth and aggregation was examined, as well as whole urine upper limits of
      metastability (ULM) for COM and calcium phosphate (CaP) in relation to the
      corresponding supersaturation (SS). RESULTS: Compared to normals, patient urine
      showed a reduced ULM in relation to SS. In contrast to men, there was no
      difference in growth inhibition. CONCLUSIONS: Reduced CaP and CaOx ULM values in
      relation to SS are a characteristic of female stone formers. This defect could
      promote stones by facilitating crystal nucleation. Abnormal inhibition may well
      be a very important cause of human nephrolithiasis.

PMID- 11967035
TI  - Renal aplasia is the predominant cause of congenital solitary kidneys.
AB  - BACKGROUND: Congenital solitary kidneys, which are susceptible to renal failure,
      have been considered mostly due to unilateral renal agenesis and partly due to
      renal aplasia. Risk of familial recurrence and of other associated anomalies is
      known to be much higher in renal agenesis than in renal aplasia. However,
      differential diagnosis between the two renal anomalies is difficult, and renal
      agenesis has been found much less frequently in ultrasound screening studies of
      fetuses than in autopsy studies. METHODS: In order to investigate the nature and
      incidence of the congenital solitary kidney, the present study performed
      ultrasound screening of the kidneys in 4000 newborn babies. A diagnosis of renal
      agenesis was made when ultrasound identified no renal parenchyma and
      renoscintigraphy showed no renal function, and renal aplasia when there was a
      renal parenchyma without any function. RESULTS: Primary screening detected 52
      babies suspected of having small kidneys and one baby with a multicystic
      dysplastic kidney, but no baby with renal agenesis. Forty-seven of the 53 babies
      underwent a second ultrasound scanning at one month of age. Three small kidneys
      in three babies further decreased in size, had no function and were diagnosed as
      renal aplasia (which has an incidence rate of one in 1300). Follow-up ultrasound
      studies showed further regression in all three, which became very hard to
      distinguish by one year of age. CONCLUSIONS: The present study showed that
      ultrasound in the neonatal period could identify the aplastic kidney, which had a
      reniform shape, not rudimentary, during the newborn period, and regressed rapidly
      thereafter. These findings indicate that most renal agenesis diagnosed clinically
      thus far might more correctly be renal aplasia.

PMID- 11967034
TI  - Sodium ferric gluconate complex in hemodialysis patients: adverse reactions
      compared to placebo and iron dextran.
AB  - BACKGROUND: Parenteral iron is often required by hemodialysis patients to
      maintain adequate iron stores. Until recently, the only available form of
      intravenous iron was iron dextran, which is associated with significant adverse
      reactions, including anaphylaxis and death. Sodium ferric gluconate complex
      (SFGC) was recently approved for use in the U.S. under FDA's priority drug
      review. This Phase IV study was designed to evaluate the safety of a single dose
      of intravenous SFGC as compared to placebo and a historical iron dextran control.
      METHODS: This multicenter, crossover, randomized, double blind, placebo
      controlled prospective comparative study was performed in hemodialysis patients
      requiring at least 125 mg of elemental iron. The historical control was obtained
      from a meta-analysis of four publications examining outcomes in patients exposed
      to iron dextran. SFGC naive patients were administered SFGC without a test dose,
      undiluted, at a rate of 125 mg over 10 minutes, and compared to placebo
      comprising bacteriostatic saline. RESULTS: A total of 2534 patients were
      enrolled. The incidence of drug intolerance (an adverse event precluding re
      exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%]
      after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P <
      0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference
      found between SFGC and placebo in serious adverse events. A single life
      threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was
      significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P =
      0.0001. CONCLUSION: SFGC is well tolerated when given by intravenous push without
      a test dose. SFGC has a significantly lower incidence of drug intolerance and
      life-threatening events as compared to previous studies using iron dextran. The
      routine use of iron dextran in hemodialysis patients should be discontinued.

PMID- 11967036
TI  - AM3 (Inmunoferon) as an adjuvant to hepatitis B vaccination in hemodialysis
      patients.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) undergoing hemodialysis
      have severe alterations in cell-mediated immunity (CMI) that increases their risk
      of contracting chronic hepatitis B virus (HBV) infection and decreases their
      protective responses to HBV vaccine. In an effort to improve the humoral response
      to an accelerated HBV vaccine protocol in these patients, the ability of an
      immunomodulator, AM3, to improve seroconversion was investigated. METHODS: A
      total of 269 patients were enrolled in a multicenter trial. All patients received
      a DNA recombinant vaccine (40 microg HBsAg/dose/day) on days 0, 10, 21, and 90.
      AM3 or placebo (3 g/day) was given orally for 30 consecutive days beginning 15
      days prior to the first vaccine dose. Anti-HBsAg titers were measured on days 120
      and 270 after the beginning of the trial. RESULTS: After one month, 207 patients
      could be evaluated and 132 patients after six months. The placebo and AM3-treated
      groups had comparable seroconversion and protective response rates one month
      after the final vaccine dose. The AM3 treatment group, but not the placebo group,
      maintained these protective titers up to six months after the final vaccine dose.
      At this time, the percentage of high responders (anti-HBsAg>100 IU/L) and mean
      anti-HBsAg titers in the AM3 group was significantly higher than in the placebo
      group. CONCLUSIONS: AM3 is a safe and easily tolerated oral agent that
      potentiates long-term serological immunity to hepatitis B in hemodialysis
      patients after vaccination.

PMID- 11967037
TI  - Role of uteroglobin G38A polymorphism in the progression of IgA nephropathy in
      Japanese patients.
AB  - BACKGROUND: Uteroglobin is a multifunctional protein and both its gene knockout
      and antisense transgenic mouse models develop the pathological and clinical
      features of IgA nephropathy. A genetic polymorphism in uteroglobin has been
      reported to be associated with progression of IgA nephropathy in a Caucasian
      population, but the findings remain controversial. METHODS: Genomic DNA was
      isolated from 595 individuals including 239 patients with IgAN, 160 patients with
      glomerulonephritis distinct from IgAN, and 196 healthy controls. The uteroglobin
      G38A genotype was determined by PCR-RFLP with Sau96I. To examine the possible
      association of uteroglobin gene polymorphism in the patients with and without
      IgAN, the uteroglobin genotype and allele frequency were compared between the two
      groups. In addition, associations between the polymorphism and blood pressure,
      proteinuria and prognosis of renal function were analyzed in the patients with
      IgAN to investigate the role of this gene polymorphism in the risk of progressive
      renal dysfunction in IgAN patients. RESULTS: The Cox proportional hazard
      regression model revealed that hypertension and proteinuria at the time of renal
      biopsy were independent risk factors for poor renal survival. Uteroglobin
      genotype was not significantly associated with the renal survival rate. However,
      in the patients with heavy proteinuria (more than 2 g/day) or in those with
      hypertension at the time of renal biopsy, the renal survival of patients with the
      GG genotype was significantly worse than the other genotypes. CONCLUSION:
      Uteroglobin GG genotype may be a genetic marker for rapid disease progression to
      end-stage renal failure, especially in the IgAN patients with heavy proteinuria
      or high blood pressure.

PMID- 11967039
TI  - Persistent rejection of peritubular capillaries and tubules is associated with
      progressive interstitial fibrosis.
AB  - BACKGROUND: We have reported that a 12-day course of high dose cyclosporine A
      treatment in thymectomized miniature swine with major histocompatibility complex
      (MHC) class I-mismatched renal allografts results in transient acute rejection
      followed by either in chronic rejection (progression group) or graft acceptance
      (recovery group). Here, we examined the differential features between both groups
      in the peritubular capillaries (PTCs) and tubules to clarify the pathogenesis of
      the progressive interstitial fibrosis in chronic rejection. METHODS: Morphometric
      and immunohistochemical studies were performed on serial renal biopsies (days 0
      to 100) obtained from both groups, focusing on the cellular infiltrate, rejection
      of PTCs and tubules, myofibroblast accumulation, and progressive interstitial
      fibrosis. RESULTS: In the progression group, acute rejection occurred by day 8
      and progressed to chronic rejection by day 100, with the development of
      interstitial fibrosis. PTC endothelial cell and tubular epithelial cell death
      associated with CD3+ cell infiltration was evident, confirmed by nick end
      labeling (TUNEL), commencing by day 8 and continuing thereafter. In acute
      rejection, destruction of PTCs and tubules accompanied by disruption of basement
      membrane (BM) occurred with capillaritis or tubulitis in areas with a severe
      cellular infiltrate. During the development of chronic rejection, capillaritis of
      PTCs and tubulitis continued by day 100, accompanied by persistent T cell
      infiltration, and the remaining PTCs and tubules exhibited progressive atrophy
      with thickening and/or lamination of BM. On day 100, identifiable PTCs and
      tubules were lost in areas of interstitial fibrosis. Proliferating (PCNA+) alpha
      actin+ myofibroblasts accumulated around PTCs, tubules and in interstitium, and
      widespread interstitial fibrosis developed by day 100. In contrast, in the
      recovery group, injured PTCs and tubules recovered by day 100 based on the
      resolution of acute rejection, and minimal loss of PTCs and tubules was evident
      by day 100 with minimal interstitial fibrosis. CONCLUSIONS: Persistent rejection
      directed at PTCs and tubules, and proliferation of myofibroblasts are prominent
      features in the progressive interstitial fibrosis in chronic rejection, and are
      probably key events in its pathogenesis.

PMID- 11967038
TI  - Increased cortisol metabolites and reduced activity of 11beta-hydroxysteroid
      dehydrogenase in patients on hemodialysis.
AB  - BACKGROUND: Patients with renal failure have symptoms assumed to be attributable
      to the accumulation of toxic endo- or xenobiotics. Most of these molecules,
      especially those with a molecular weight>300 D, have not been identified. In
      addition to excretion, the kidney is involved in some defined metabolic
      processes. In the cortical collecting duct, the enzyme 11beta-hydroxysteroid
      dehydrogenase type 2 (11beta-HSD2) interconverts cortisol (F) and cortisone (E),
      and the metabolites of these glucocorticoids, tetrahydrocortisol (THF), 5alpha
      tetrahydrocortisol (5alpha-THF) and tetrahydrocortisone (THE), are excreted in
      urine. We hypothesized that first, these metabolites accumulate and second, their
      concentration pattern changes in patients on hemodialysis. METHODS: THF, 5alpha
      THF, THE, F and E were measured in plasma of 63 patients on dialysis and in 34
      healthy controls by gas-chromatography-mass spectrometry (GC/MS). In 11 patients,
      the metabolite clearance was determined during high flux hemodialysis by using a
      population pharmacokinetic approach. RESULTS: Mean plasma concentrations of THF,
      5alpha-THF and THE were more than five times higher and those of E lower in
      patients than in controls. The ratios of (THF + 5alpha-THF)/THE and F/E were
      increased in patients, indicating a reduced activity of 11beta-HSD2.
      Intradialytic clearances were between 120 and 300 mL/min and not sufficient to
      normalize the steroid concentrations. CONCLUSION: Patients on hemodialysis
      exhibit pronounced increases in THF, 5alpha-THF and THE concentrations in plasma
      with insufficient removal during dialysis. Due to a reduced 11beta-HSD2 activity,
      an abnormal pattern of the concentrations of these cortisol and cortisone
      metabolites is observed. Since many signs and symptoms in uremic patients
      resemble those observed in subjects with glucocorticoid excess, the clinical
      relevance of the high concentrations of these glucocorticoid metabolites deserves
      further investigation.

PMID- 11967040
TI  - Acute graft pyelonephritis and long-term kidney allograft outcome.
AB  - BACKGROUND: Long-term graft function is the result of multiple parameters,
      including both immune and non-immune components, which have a beneficial or
      detrimental potential. Among these, despite its frequency and theoretical
      interest (expression of "danger signals" in the graft itself), the effects of
      acute graft pyelonephritis (AGPN) on immediate and long-term outcome have not
      been studied in a large series. This article reviews a cohort of 1387 consecutive
      primary renal transplant recipients. METHODS: The objective of the study was to
      define the risk factor for AGPN, the risk profile for recurrence, and the impact
      of AGPN on long-term graft survival. According to a higher risk for AGPN in
      females during their follow-up, statistical analyses (Cox model, and multiple
      regression analysis) were performed by recipient sex strata. RESULTS:
      Multivariate analysis showed that CMV infection was the only risk factor for AGPN
      occurrence. AGPN occurred in 13% of the graft recipients during their follow-up.
      Taken as a whole, AGPN was not associated with a significantly poor long-term
      outcome. However, when assessed in more detail, the outcome of this population
      was found to be more complex and to depend on several factors. Early AGPN (during
      the first 3 months) was significantly detrimental for graft outcome,
      independently of acute rejection episodes. Moreover, E. coli involvement in a
      first episode was linked to an increased AGPN recurrence. CONCLUSION: This
      analysis did not support the concept that with current immunosuppression, strong
      "danger signals" such as those derived from bacteria within an allograft, are
      instrumental in initiating acute or chronic rejection.

PMID- 11967041
TI  - Hypocholesterolemia is a significant predictor of death in a cohort of chronic
      hemodialysis patients.
AB  - BACKGROUND: Although hypocholesterolemia is common in chronic hemodialysis
      patients, its effect on survival has not been studied in a large patients
      population. METHODS: A cohort of chronic hemodialysis patients (N = 1167) was
      prospectively followed from January 1991 to January 2001. The survival impact of
      this cohort, who were divided according to different baseline levels of serum
      cholesterol, were calculated with the multivariate Cox proportional hazard
      analysis after adjusting for baseline clinical and laboratory variables. RESULTS:
      During the study period, 567 (48.6%) patients died. The mean (SD) baseline level
      of serum cholesterol was 171.0 (40.8) mg/dL and ranged from 76 to 378 mg/dL. The
      five-year survival rate was highest (0.812) in the subgroup that had a serum
      cholesterol range of 200 to 219 mg/dL and was lowest (0.608) in the subgroup with
      serum cholesterol values of <140 mg/dL. The five-year survival rate was 0.735 in
      the subgroup with serum cholesterol of > or =220 mg/dL. Serum cholesterol was a
      significant predictor of death with an adjusted hazards ratio (95% confidence
      interval) was 0.939 (0.891 to 0.989). In a subgroup of patients with serum
      albumin values > or =4.5 g/dL (N = 128), the adjusted hazards ratio was even
      greater at 1.370 (1.105 to 1.692). Other than sex, body mass index and serum
      albumin were significant determinants of baseline levels of serum cholesterol.
      CONCLUSIONS: Hypocholesterolemia was an independent predictor of death in
      patients on chronic hemodialysis. This impact of hypercholesterolemia on survival
      was only evident in a subgroup of patients whose serum albumin was more than 4.5
      g/dL.

PMID- 11967042
TI  - Influence of mycophenolic acid and tacrolimus on homocysteine metabolism.
AB  - BACKGROUND: The effect of mycophenolate mofetil (MMF) on homocysteine (Hcy)
      metabolism is unknown. METHODS: This in vitro study examined whether mycophenolic
      acid or tacrolimus influences the formation of Hcy as determined by measuring the
      total Hcy (tHcy) concentrations in supernatants of human renal proximal tubule
      epithelial cells. Cells were incubated with and without vitamins (folate, vitamin
      B6 and B12) in the presence of low or high methionine concentrations at different
      mycophenolic acid (0, or 5, or 20 microg/mL) or tacrolimus (0, or 10, or 25
      ng/mL) concentrations for 24, 48 or 72 hours. The concentration of tHcy in
      culture supernatants was measured by a fluorescence polarization immunoassay. The
      effect of MMF on tHcy plasma levels was also examined in 454 kidney graft
      recipients. RESULTS: Comparisons of tHcy levels in culture supernatants over time
      by four way ANOVA showed that methionine concentration (P < 0.00001), time (P <
      0.00001), vitamins (P = 0.002728), and mycophenolic acid concentration (P =
      0.000095) were all significant predictors of tHcy concentrations. This was due to
      significantly lower tHcy levels with using mycophenolic acid at a high
      concentration versus control at the 48- and 72-hour time points. By contrast,
      tacrolimus showed no effect in vitro. Among the kidney graft recipients, male
      patients on MMF therapy showed lower plasma tHcy concentrations as compared to
      those on azathioprine (P = 0.03). CONCLUSION: Our study suggests a tHcy lowering
      effect of MMF in male transplant recipients, which improves the cardiovascular
      disease risk profile, whereas tacrolimus showed no effect.

PMID- 11967043
TI  - Value of static venous pressure for predicting arteriovenous graft thrombosis.
AB  - BACKGROUND: Static venous pressure elevation has been shown to have both high
      sensitivity and high specificity for hemodialysis arteriovenous (AV) graft venous
      anastomosis stenosis. However, it is not known how well static venous pressure
      elevation predicts subsequent AV graft thrombosis. METHODS: Monthly static venous
      pressure measurements were made during two consecutive dialysis sessions in all
      patients with a functioning upper extremity AV graft in two hemodialysis units
      during a 16-month period. Static venous pressure was normalized to systolic blood
      pressure and corrected for the height difference between the AV graft and the
      dialysis machine pressure transducer to yield the static venous pressure ratio
      (SVPR). RESULTS: Fifty-four patients (38%) had a thrombotic event during the
      study period and thus were labeled as clotters. Among the clotters, SVPR just
      prior to thrombosis was 0.51 +/- 0.16 (mean +/- SD), and mean time to thrombosis
      following an elevated SVPR (> or =0.4) was 118 +/- 106 days. Receiver operating
      characteristic (ROC) curves were generated using the sensitivities and
      specificities of a range of SVPR values for access thrombosis within one, two,
      three and four months. The areas under the curve (AUCs) for the ROC curves ranged
      from 0.557 to 0.638, reflecting the absence of SVPR values with both high
      sensitivity and high specificity for access thrombosis. An increase in SVPR over
      time was not a better predictor of access thrombosis than absolute SVPR.
      CONCLUSION: Static venous pressure measurement is not an optimal screening test
      for identifying AV grafts at risk for thrombosis.

PMID- 11967044
TI  - Of mice and men: murine models of anti-GBM antibody nephritis.

PMID- 11967046
TI  - The homocysteine confusion: now, more is better?

PMID- 11967045
TI  - Dietary protein intake significantly affects the serum creatinine concentration.

PMID- 11967048
TI  - Daily hemodialysis and nutritional status.

PMID- 11967049
TI  - Moderate hyperhomocysteinemia and oxidative stress.

PMID- 11967050
TI  - Treatment of chronic tubulointerstitial disease: a new concept.

PMID- 11967051
TI  - In vitro antibiotic susceptibility of bacteria isolated from EUS-affected fishes
      in India.
AB  - AIMS: Twelve antibiotics were evaluated for in vitro sensitivity against 16
      bacterial strains isolated from surface lesions of fishes affected with epizootic
      ulcerative syndrome (EUS). METHODS AND RESULTS: Disc diffusion assay in Mueller
      Hinton agar showed that the pseudomonads and aeromonads were mainly resistant to
      penicillin, ampicillin and erythromycin. Additionally, some were resistant to
      gentamycin and amoxycillin. However, resistance towards antibiotics previously
      recommended for EUS treatment, such as oxytetracycline and chloramphenicol, was
      not observed. Four aeromonads and two pseudomonads were found to induce ulcers
      when injected intramuscularly in healthy Anabas testudineus. CONCLUSIONS: All six
      pathogenic isolates were sensitive towards oxytetracycline, chloramphenicol and
      nalidixic acid. Oxytetracycline seems to be an effective antibiotic, and further
      investigations to determine the mode of treatment and dose appear to be
      worthwhile.

PMID- 11967052
TI  - Improved polygalacturonase production from Bacillus sp. MG-cp-2 under submerged
      (SmF) and solid state (SSF) fermentation.
AB  - AIMS: To investigate the effect of amino acids, vitamins and surfactants on
      polygalacturonase production from Bacillus sp. MG-cp-2 under submerged (SmF) and
      solid state fermentation (SSF). METHODS AND RESULTS: Bacillus sp. MG-cp-2 was
      isolated from the outer covering of the seeds of Celastrus paniculatus. Out of
      the various surfactants, amino acids and vitamins, Tween-60, DL-serine and folic
      acid maximally enhanced polygalacturonase production by 2.7-fold (240.0 U x ml(
      1)), 4.0-fold (360.0 U x ml(-1)) and 3.8-fold (342.0 U x ml(-1)) respectively,
      under submerged fermentation (SmF). In solid state fermentation (SSF), Tween-80,
      pyridoxine and DL-ornithine monohydrochloride induced highest enzyme production
      up to 1.73-fold (6956.5 U x g(-1)), 5.3-fold (21224.4 U x g(-1)) and 5.74-fold
      (23076.9 U x g(-1)), respectively. CONCLUSION: Amino acids and their analogues,
      vitamins and surfactants effect significantly polygalacturonase production by
      Bacillus sp. MG-cp-2 when grown under submerged (SmF) and solid state
      fermentation (SSF) conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: The study
      provides useful information about regulation of polygalacturonase biosynthesis in
      Bacillus sp. MG-cp-2, which appears to be an interplay of nutritional and
      physical factors. Alkaline polygalacturonase from Bacillus sp. MG-cp-2 will be
      extremely useful in the treatment of alkaline pectic waste waters from vegetable
      and fruit processing industries and in degumming of bast fibres.

PMID- 11967053
TI  - Typing of Saccharomyces cerevisiae and Kloeckera apiculata strains from Aglianico
      wine.
AB  - AIMS: Kloeckera apiculata and Saccharomyces cerevisiae yeast species are
      dominant, respectively, at the early and at the following stages of wine
      fermentation. In the present study, PCR fingerprinting and NTS region
      amplification and restriction were applied as techniques for monitoring yeast
      population performing Aglianico of Vulture grape must fermentation. METHODS AND
      RESULTS: Thirty S. cerevisiae and 30 K. apiculata strains were typed by PCR
      fingerprinting with (GAC)5 and (GTG)5 primers and by complete NTS region
      amplification followed by restriction with HaeIII and MspI enzymes. S. cerevisiae
      strains generated two patterns with (GAC)5 primer, while (GTG)5 primer yielded a
      higher genetic polymorphism. Conversely, in K. apiculata Aglianico wine strains
      (GAC)5 and (GTG)5 primers generated the same profile for all strains. Restriction
      analysis of the amplified NTS region gave the same profile for all strains within
      the same species, except for one strain of S. cerevisiae. CONCLUSIONS: The PCR
      fingerprinting technique was useful in discriminating at strain level S.
      cerevisiae, particularly with the primer (GTG)5. RFLP patterns generated from the
      NTS region of the two species can be more easily compared than the patterns
      resulting from PCR fingerprinting, thus RFLP is more suitable for the rapid
      monitoring of the species involved in different stages of fermentation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The molecular techniques used allow
      discrimination of S. cerevisiae at strain level and monitoring of the ratio of S.
      cerevisiae/K. apiculata during the fermentation process. Thus, their application
      can assure technological adjustments in a suitable time.

PMID- 11967055
TI  - Production, purification and characterization of an extracellular keratinase from
      Lysobacter NCIMB 9497.
AB  - AIMS: The aim of this study was to determine the keratinolytic ability of a range
      of bacteria and subsequently, to characterize the keratinase showing the greatest
      biotechnological potential. METHODS AND RESULTS: Nine bacteria, reported to
      produce extracellular proteases, were screened for production of keratinases. Of
      these, Lysobacter NCIMB 9497 exhibited the highest keratinolytic activity. The
      keratinase from this strain (Mr 148 kDa) was purified and characterized. Optimum
      activity occurred at 50 degrees C; no inhibition was demonstrated by
      phenylmethylsulphonyl fluoride (PMSF), but inhibition by EDTA was demonstrated.
      CONCLUSIONS: This study indicates that keratinase is a metalloprotease with a
      high degree of keratinolytic activity and stability. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This is the first detailed report of a metalloprotease with
      keratinolytic activity. The novel reaction mechanism, degree of keratinolytic
      activity and stability indicate considerable biotechnological potential in the
      leather industry, and in the processing of poultry waste.

PMID- 11967054
TI  - Microbial status and rumen enzyme profile of crossbred calves fed on different
      microbial feed additives.
AB  - AIMS: To test various microbial cultures as cattle feed additives. METHODS AND
      RESULTS: Four groups of newly born crossbred calves (average body weight 23.5 kg)
      were reared on green berseem and calf starter which was devoid of cereal grains.
      Milk was fed up to 8 weeks of age, starting with one tenths and gradually
      reducing to one twentieths of the body weight. One hundred millilitres of
      microbial feed additive or 100 g fermented feed was fed to the animals of group 2
      (curd containing lactic acid bacteria at 10(8) cfu x ml(-1)), group 3
      (Saccharomyces cerevisiae NCDC-49 at 10(6) cfu x ml(-1)) and group 4
      (Lactobacillus acidophilus-15 at 10(8) cfu x ml(-1)). Group 1 served as control.
      The incidence and duration of diarrhoea was lower in the animals of probiotic fed
      groups as compared to control group. Out of three microbial feed additives, yeast
      feeding showed maximum suppression of diarrhoea followed by Lactobacillus and
      curd. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: There was no effect of
      probiotic feeding on the log number of cells of lactic acid bacteria, yeast and
      coliform bacteria in the faeces and rumen liquor at any age. The activities of
      carboxymethylcellulase, xylanase, beta-glucosidase, alpha-glucosidase, alpha
      amylase, protease, urease and pH of the rumen liquor remained unaffected by
      probiotic feeding at all ages tested in this experiment.

PMID- 11967056
TI  - Aspergillus section Flavi populations from field maize in Argentina.
AB  - AIMS: Populations of Aspergillus section Flavi were studied from a commercial
      field of maize in Rio Cuarto, Cordoba, Argentina. METHODS AND RESULTS: The
      Aspergillus species were isolated from soil, debris and insects during three
      periods: pre-planting, growing maize and post-harvest. The colony count from non
      rhizospheric soil in the pre-planting period was higher than in growing maize and
      the post-harvest period. Debris samples analysed during all periods showed
      similar infection percentages for Aspergillus section Flavi. The samples of
      insects collected during the maize-growing period showed a lower percentage of
      Aspergillus isolates than the samples from soil and debris. Aflatoxigenic strains
      were present in lower levels in each component of the agroecosystem studied. All
      the strains that produced sclerotia were L strains. CONCLUSIONS: In this field
      agroecosystem, the only strains with a high probability for transfer to the
      storage agroecosystem were L strains with low toxigenic potential. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Maize pre-harvest contamination with aflatoxigenic
      inoculum was not significant.

PMID- 11967057
TI  - Manipulation of temperature and illumination conditions for enhanced beta
      carotene production by mutant 32 of Rhodotorula glutinis.
AB  - AIMS: Enhancement in the production of beta-carotene by the hyper producer mutant
      32 of Rhodotorula glutinis by manipulation of temperature and illumination.
      METHODS AND RESULTS: Growth and beta-carotene production was investigated in a 1
      litre fermenter at different temperature and illumination conditions. The optimum
      temperature for growth and beta-carotene production was 30 and 20 degrees C,
      respectively. At 30 degrees C, beta-carotene production was 125 +/- 2 mg l-1 and
      accounted for 66% of the total carotenoids in 72 h; at 20 degrees C, it was 250
      +/- 7 mg l-1 and accounted for 92% of total carotenoid content. Continuous
      illumination of the fermenter by 1000 lx white light hampered growth as well as
      carotenoid synthesis. At 30 degrees C, illuminating the fermenter in late
      logarithmic phase resulted in a 58% increase in beta-carotene production with a
      concurrent decrease in torulene; at 20 degrees C, however, it showed no
      appreciable increase. SIGNIFICANCE AND IMPACT OF THE STUDY: Proper manipulation
      of culture conditions enhanced beta-carotene production by R. glutinis which
      makes it a significant source of beta-carotene.

PMID- 11967058
TI  - PCR/restriction fragment length polymorphism (RFLP) typing of human and poultry
      Campylobacter jejuni strains.
AB  - AIMS: The PCR/RFLP typing of 156 isolates Campylobacter jejuni originating from
      poultry and humans was performed (101 human and 55 poultry strains). METHODS AND
      RESULTS: On the basis of restrictive digest, six types were identified with AfaI,
      seven types with MboI and five types with HaeIII. With a combination of these
      three enzymes, 22 types were found. In human strains, the most frequently
      occurring types were Cj.4 (28%), Cj.1 (19%), Cj. 13 (13%) and Cj. 2 (5%). In the
      case of poultry strains, the most frequent types were Cj. 1 (34%), Cj. 11 (22%),
      C.j. 21 (16%) and Cj. 15 (11%). CONCLUSIONS: The findings support the hypothesis
      that poultry is a significant source but not sole source of Campylobacter sp. in
      relation to humans. SIGNIFICANCE AND IMPACT OF THE STUDY: The typing of
      Campylobacter sp. forms the basis for an evaluation of the current state and risk
      assessment of various Campylobacter sp. sources in relation to humans.

PMID- 11967059
TI  - Histopathological methods for the investigation of microbial communities
      associated with disease lesions in reef corals.
AB  - AIMS: To determine the spatial structure of microbial communities associated with
      disease lesions of reef corals (Scleractinia). METHODS AND RESULTS: Agarose pre
      embedding preserved the structure of the disease lesion and surrounding tissues
      prior to demineralization of the carbonate exoskeleton and embedding in resin.
      Fluorescence in situ hybridization (FISH) was used to localize bacteria in the
      lesions of various diseases. CONCLUSIONS: The techniques successfully preserved
      the in situ spatial structure of degenerated coral tissues. In one case (white
      plague disease), significant bacterial populations were found only in fragmented
      remnants of degenerated coral tissues at the lesion boundary that would not have
      been detected using conventional histopathological techniques. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Determining the composition, spatial structure and dynamics
      of microbial communities within the disease lesions is necessary to understand
      the process of disease progression. The methods described may be applicable to a
      wide range of diseases involving necrotic lesion formation and requiring
      extensive tissue processing, such as skeleton demineralization.

PMID- 11967060
TI  - Optimizing enrichment conditions for the isolation of Escherichia coli O157 in
      soils by immunomagnetic separation.
AB  - AIMS: To compare a range of enrichment broths and enrichment temperatures for the
      isolation of Escherichia coli O157 by immunomagnetic separation (IMS) from sandy,
      loam and clay soils. METHODS AND RESULTS: Soils were spiked with cocktails of
      four atoxigenic strains of E. coli O157 and four strains of commensal E. coli.
      The organisms were stressed by subjecting soils to cycles of freeze/thawing,
      followed by drying at 20 degrees C for up to 4 days. Nine enrichment broths were
      trialled based on buffered peptone water, tryptone soya broths and EC broths
      supplemented with a range of selective additions. Enrichments were incubated for
      6 h and assessed by target recovery after IMS on cefixime tellurite sorbitol
      MacConkey agar (CTSMAC) incubated at 37 degrees C for 24 h. A comparison of
      enrichment temperatures (37 and 42 degrees C) was also performed. Buffered
      peptone water (with or without vancomycin) and tryptone soya broth (with or
      without novobiocin) gave significant increases in recovery of E. coli O157
      compared to others tested. In addition, broths incubated at 42 degrees C were
      superior to those at 37 degrees C for the recovery of E. coli O157. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study showed that sub-lethally damaged E. coli O157
      surviving in soil can be sensitive to antimicrobial additions. The choice and
      concentration of these additions is vitally important to optimize target
      recovery. Some IMS protocols, established for the isolation of E. coli O157, may
      be unsuitable for the examination of soil samples.

PMID- 11967061
TI  - Improvement for the production of clavulanic acid by mutant Streptomyces
      clavuligerus.
AB  - AIMS: To improve the production of clavulanic acid through the development of
      strains, the selection of a production medium and a pH shift strategy in a
      bioreactor. METHODS AND RESULTS: Streptomyces clavuligerus mutant 15 was selected
      by antibacterial activities. As a result of pH control in a 2.5 l bioreactor, the
      highest productivity (3.37 microg x ml(-1) x h(-1)) was obtained at a controlled
      pH of 7.0. CONCLUSIONS: The highest level of production obtained was an increase
      of about 36% compared with a non-controlled pH. When the production of clavulanic
      acid reached the maximum level, the pH was shifted from 7.0 to 6.0 for reduction
      in decomposition rate. The maximum concentration of clavulanic acid was
      maintained for 24 h as a result of the pH shift control, and a significant
      reduction in the decomposition of clavulanic acid was obtained. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Clavulanic acid decomposition was considerably reduced as a
      result of the pH shift control. The results of this study can be applied for the
      efficient production of beta-lactamase inhibitory antibiotics.

PMID- 11967062
TI  - Phylogenetic relationships among strains of the entomopathogenic fungus, Nomuraea
      rileyi, as revealed by partial beta-tubulin sequences and inter-simple sequence
      repeat (ISSR) analysis.
AB  - AIMS: To elucidate the phyletic relationships among three members of the
      entomogenous fungal genus, Nomuraea, with an emphasis on N. rileyi. METHODS AND
      RESULTS: Relationships were evaluated by analysis of the beta-tubulin gene and of
      inter-simple sequence repeats (ISSR). The amplification product of the partial
      beta-tubulin gene was larger for N. atypicola than for N. rileyi, and sequencing
      of this gene fragment confirmed that N. atypicola possesses approximately 25 more
      nucleotides than N. rileyi and N. anemonoides. Based on neighbor joining and
      bootstrap analysis of the partial beta-tubulin gene, N. atypicola failed to form
      a monophyletic grouping with the other two species of Nomuraea. In contrast, the
      single isolate of N. anemonoides clustered with the N. rileyi isolates, and both
      taxa grouped with Epichloe typhina (Hypocreales: Clavicipitaceae). Results from
      this study suggested that N. rileyi and N. anemonoides are closely related to the
      Clavicipitaceae. In contrast, evidence indicated that N. atypicola is not closely
      related to this family, and that this taxon is not a Nomuraea. Based on the 83
      polymorphic loci of ISSR, it was observed that isolates of N. rileyi from diverse
      geographical origins were distinctly different from both N. atypicola and N.
      anemonoides. Considerable heterogeneity was observed in the 18 isolates of N.
      rileyi tested, and several clusters contained isolates from disparate
      geographical locations and hosts. However, three isolates from the Philippines
      (three host species) and three strains isolated from velvetbean caterpillar
      (Anticarsia gemmatalis) larvae in South America did cluster together. Two other
      strains from Brazil (isolated from Spodoptera spp.) were distinct from the
      velvetbean caterpillar isolates from South America. CONCLUSIONS, SIGNIFICANCE AND
      IMPACT OF THE STUDY: The beta-tubulin gene was generally too conserved to resolve
      intraspecies variability. However, ISSR did identify polymorphisms among the
      isolates of N. rileyi tested. The results of this study indicate that ISSR may be
      used as robust molecular markers for studying the population genetics of this
      entomopathogenic fungus.

PMID- 11967063
TI  - Giardia and Cryptosporidium removal from waste-water by a duckweed (Lemna gibba
      L.) covered pond.
AB  - AIMS: To determine the ability of duckweed ponds used to treat domestic waste
      water to remove Giardia and Cryptosporidium. METHODS AND RESULTS: The influent
      and effluent of a pond covered with duckweed with a 6 day retention time was
      tested for Giardia cysts, Cryptosporidium oocysts, faecal coliforms and
      coliphage. Giardia cysts and Cryptosporidium oocysts were reduced by 98 and 89%,
      respectively, total coliforms by 61%, faecal coliforms by 62% and coliphage by
      40%. There was a significant correlation between the removal of Giardia cysts and
      Cryptospordium oocysts by the pond (P < 0.001). Influent turbidity and parasite
      removal were also significantly correlated (Cryptosporidium and turbidity,
      P=0.05; Giardia and turbidity, P=0.01). CONCLUSIONS: The larger organisms
      (parasites) probably settled to the bottom of the pond, while removal of smaller
      bacteria and coliphages in the pond was not as effective. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Duckweed ponds may play an important role in wetland systems for
      reduction of Giardia and Cryptosporidium.

PMID- 11967064
TI  - Oxidative protein folding in bacteria.
AB  - Ten years ago it was thought that disulphide bond formation in prokaryotes
      occurred spontaneously. Now two pathways involved in disulphide bond formation
      have been well characterized, the oxidative pathway, which is responsible for the
      formation of disulphides, and the isomerization pathway, which shuffles
      incorrectly formed disulphides. Disulphide bonds are donated directly to unfolded
      polypeptides by the DsbA protein; DsbA is reoxidized by DsbB. DsbB generates
      disulphides de novo from oxidized quinones. These quinones are reoxidized by the
      electron transport chain, showing that disulphide bond formation is actually
      driven by electron transport. Disulphide isomerization requires that incorrect
      disulphides be attacked using a reduced catalyst, followed by the redonation of
      the disulphide, allowing alternative disulphide pairing. Two isomerases exist in
      Escherichia coli, DsbC and DsbG. The membrane protein DsbD maintains these
      disulphide isomerases in their reduced and thereby active form. DsbD is kept
      reduced by cytosolic thioredoxin in an NADPH-dependent reaction.

PMID- 11967065
TI  - Are the PE-PGRS proteins of Mycobacterium tuberculosis variable surface antigens?
AB  - Mycobacterium tuberculosis H37Rv contains 67 PE-PGRS genes, with multiple tandem
      repetitive sequences, encoding closely related proteins that are exceptionally
      rich in glycine and alanine. As no functional information was available, 10 of
      these genes were selected and shown to be expressed in vitro by reverse
      transcription-polymerase chain reaction (RT-PCR). Antibodies against five PE-PGRS
      proteins, raised in mice by DNA vaccination, detected single proteins when the
      same plasmid constructs used for immunization were expressed in epithelial cells
      or in reticulocyte extracts, confirming that the PE-PGRS proteins are antigenic.
      As expected from the conserved repetitive structure, the antibodies cross-reacted
      with more than one PE-PGRS protein, suggesting that different proteins share
      common epitopes. PE-PGRS proteins were detected by West-ern blotting in five
      different mycobacterial species (M. tuberculosis, M. bovis BCG, M. smegmatis, M.
      marinum and M. gordonae) and 11 clinical isolates of M. tuberculosis. Whole
      genome comparisons of M. tuberculosis predicted allelic diversity in the PE-PGRS
      family, and this was confirmed by immunoblot studies as size variants were
      detected in clinical strains. Subcellular fractionation studies and
      immunoelectron microscopy localized many PE-PGRS proteins in the cell wall and
      cell membrane of M. tuberculosis. The data suggest that some PE-PGRS proteins are
      variable surface antigens.

PMID- 11967066
TI  - HSF and Msn2/4p can exclusively or cooperatively activate the yeast HSP104 gene.
AB  - In an effort to understand how an accurate level of stress-specific expression is
      obtained, we studied the promoter of the yeast HSP104 gene. Through 5' deletions,
      we defined a 334 bp fragment upstream of the first coding AUG as sufficient and
      essential for maximal basal activity and a 260 bp fragment as sufficient and
      essential for heat shock responsiveness. These sequences contain heat shock
      elements (HSEs) and stress response elements (STREs) that cooperate to achieve
      maximal inducible expression. However, in the absence of one set of factors (e.g.
      in msn2Deltamsn4Delta cells) proper induction is obtained exclusively through
      HSEs. We also show that HSP104 is constitutively derepressed in ras2Delta cells.
      This derepression is achieved exclusively through activation of STREs, with no
      role for HSEs. Strikingly, in ras2Deltamsn2Deltamsn4Delta cells the HSP104
      promoter is also derepressed, but in this strain derepression is mediated through
      HSEs, showing the flexibility and adaptation of the promoter. Thus, appropriate
      transcription of HSP104 is usually obtained through cooperation between the
      Msn2/4/STRE and the HSF/ HSE systems, but each factor could activate the promoter
      alone, backing up the other. Transcription control of HSP104 is adaptive and
      robust, ensuring proper expression under extreme conditions and in various
      mutants.

PMID- 11967067
TI  - The Xanthomonas oryzae pv. lozengeoryzae raxP and raxQ genes encode an ATP
      sulphurylase and adenosine-5'-phosphosulphate kinase that are required for
      AvrXa21 avirulence activity.
AB  - Xanthomonas oryzae pv. oryzae (Xoo) Philippine race 6 (PR6) is unable to cause
      bacterial blight disease on rice lines containing the rice resistance gene Xa21
      but is virulent on non-Xa21 rice lines, indicating that PR6 carries avirulence
      (avrXa21) determinants required for recognition by XA21. Here we show that two
      Xoo genes, raxP and raxQ, are required for AvrXa21 activity. raxP and raxQ, which
      reside in a genomic cluster of sulphur assimilation genes, encode an ATP
      sulphurylase and APS (adenosine-5'-phosphosulphate) kinase. These enzymes
      function together to produce activated forms of sulphate, APS and PAPS (3'
      phosphoadenosine-5'-phosphosulphate). Xoo PR6 strains carrying disruptions in
      either gene, PR6DeltaraxP or PR6DeltaraxQ, are unable to produce APS and PAPS and
      are virulent on Xa21-containing rice lines. RaxP and RaxQ are similar to the
      bacterial symbiont Sinorhizobium meliloti host specificity proteins, NodP and
      NodQ and the Escherichia coli cysteine synthesis proteins CysD, CysN and CysC.
      The APS and PAPS produced by RaxP and RaxQ are used for both cysteine synthesis
      and sulphation of other molecules. Mutation in Xoo xcysI, a homologue of
      Escherichia coli cysI that is required for cysteine synthesis, blocked APS- or
      PAPS-dependent cysteine synthesis but did not affect AvrXa21 activity, suggesting
      that AvrXa21 activity is related to sulphation rather than cysteine synthesis.
      Taken together, these results demonstrate that APS and PAPS production plays a
      critical role in determining avirulence of a phytopathogen and reveal a
      commonality between symbiotic and phytopathogenic bacteria.

PMID- 11967068
TI  - Molecular characterization of phenyllactate dehydratase and its initiator from
      Clostridium sporogenes.
AB  - The heterotrimeric phenyllactate dehydratase from Clostridium sporogenes, FldABC,
      catalyses the reversible dehydration of (R)-phenyllactate to (E)-cinnamate in two
      steps: (i) CoA-transfer from the cofactor cinnamoyl-CoA to phenyllactate to yield
      phenyllactyl-CoA and the product cinnamate mediated by FldA, a (R)-phenyllactate
      CoA-transferase; followed by (ii) dehydration of phenyllactyl-CoA to cinnamoyl
      CoA mediated by heterodimeric FldBC, a phenyllactyl-CoA dehydratase.
      Phenyllactate dehydratase requires initiation by ATP, MgCl2 and a reducing agent
      such as dithionite mediated by an extremely oxygen-sensitive initiator protein
      (FldI) present in the cell-free extract. All four genes coding for these proteins
      were cloned and shown to be clustered in the order fldAIBC, which shares over 95%
      sequence identity of nucleotide and protein levels with a gene cluster detected
      in the genome of the closely related Clostridium botulinum Hall strain A. FldA
      shows sequence similarities to a new family of CoA-transferases, which apparently
      do not form covalent enzyme CoA-ester intermediates. An N-terminal Strep II-Tag
      containing enzymatically active FldI was overproduced and purified from
      Escherichia coli. FldI was characterized as a homodimeric protein, which contains
      one [4Fe-4S]1+/2+ cluster with an electron spin S = 3/2 in the reduced form. The
      amino acid sequence as well as the chemical and EPR-properties of the pure
      protein are very similar to those of component A of 2-hydroxyglutaryl-CoA
      dehydratase from Acidaminococcus fermentans (HgdC), which was able to replace
      FldI in the activation of phenyllactate dehydratase. Only in the oxidized state,
      FldI and component A exhibit significant ATPase activity, which appears to be
      essential for unidirectional electron transfer. Both subunits of phenyllactyl-CoA
      dehydratase (FldBC) show significant sequence similarities to both subunits of 2
      hydroxyglutaryl-CoA dehydratase (HgdAB). The fldAIBC gene cluster resembles the
      hadAIBC gene cluster in the genome of Clostridium difficile and the hadABC,I
      genes in C. botulinum. The four subunits of these deduced 2-hydroxyacid
      dehydratases (65-81% amino acid sequence identity between the had genes) probably
      code for a 2-hydroxyisocaproate dehydratase involved in leucine fermentation.
      This enzyme could be the target for metronidazole in the treatment of
      pseudomembranous enterocolitis caused by C. difficile.

PMID- 11967069
TI  - Candida albicans Als1p: an adhesin that is a downstream effector of the EFG1
      filamentation pathway.
AB  - Filamentation and adherence to host cells are critical virulence factors of
      Candida albicans. Multiple filamentation regulatory pathways have been discovered
      in C. albicans using Saccharomyces cerevisiae as a model. In S. cerevisiae, these
      pathways converge on Flo11p, which functions as a downstream effector of
      filamentation and also mediates cell-cell adherence (flocculation). In C.
      albicans, such effector(s) have not yet been identified. Here, we demonstrate
      that the cell surface protein Als1p is an effector of filamentation in C.
      albicans. We show that Als1p expression is controlled by the transcription factor
      Efg1p, which is known to be a key regulator of filamentation in C. albicans.
      Further, disruption of ALS1 inhibited filamentation, and autonomous expression of
      Als1p restored filamentation in an efg1 homozygous null mutant. Thus, Als1p
      functions as a downstream effector of the EFG1 filamentation pathway. In
      addition, we found that Als1p mediates both flocculation and adherence of C.
      albicans to endothelial cells in vitro. As a cell surface glycoprotein that
      mediates filamentation and adherence, Als1p has both structural and functional
      similarity to S. cerevisiae Flo11p. Consistent with our in vitro results, Als1p
      was required for both normal filamentation and virulence in the mouse model of
      haematogenously disseminated candidiasis.

PMID- 11967070
TI  - Identification of Pseudomonas syringae pv. tomato genes induced during infection
      of Arabidopsis thaliana.
AB  - Phytopathogenic bacteria possess a large number of genes that allow them to grow
      and cause disease on plants. Many of these genes should be induced when the
      bacteria come in contact with plant tissue. We used a modified in vivo expression
      technology (IVET) approach to identify genes from the plant pathogen Pseudomonas
      syringae pv. tomato that are induced upon infection of Arabidopsis thaliana and
      isolated over 500 in planta-expressed (ipx) promoter fusions. Sequence analysis
      of 79 fusions revealed several known and potential virulence genes, including
      hrp/hrc, avr and coronatine biosynthetic genes. In addition, we identified
      metabolic genes presumably important for adaptation to growth in plant tissue, as
      well as several genes with unknown function that may encode novel virulence
      factors. Many ipx fusions, including several corresponding to novel genes, are
      dependent on HrpL, an alternative RNA polymerase sigma factor that regulates the
      expression of virulence genes. Expression analysis indicated that several ipx
      fusions are strongly induced upon inoculation into plant tissue. Disruption of
      one ipx gene, conserved effector locus (CEL) orf1, encoding a putative lytic
      murein transglycosylase, resulted in decreased virulence of P. syringae. Our
      results demonstrate that this screen can be used successfully to isolate genes
      that are induced in planta, including many novel genes potentially involved in
      pathogenesis.

PMID- 11967071
TI  - Over 1000 genes are involved in the DNA damage response of Escherichia coli.
AB  - Changes in gene expression after treatment of Escherichia coli cultures with
      mitomycin C were assessed using gene array technology. Unexpectedly, a large
      number of genes (nearly 30% of all genes) displayed significant changes in their
      expression level. Analysis and classification of expression profiles of the
      corresponding genes allowed us to assign this large number of genes into one or
      two dozen small clusters of genes with similar expression profiles. This
      assignment allowed us to describe systematically the changes in the level of gene
      expression in response to DNA damage. Among the damage-induced genes, more than
      100 are novel. From those genes involved in DNA metabolism that have not
      previously been shown to be induced by DNA damage, the mutS gene involved in
      mismatch repair is especially noteworthy. In addition to the SOS response, we
      observed the induction of other stress response pathways, such as those of
      oxidative stress and osmotic protection. Among the genes that are downregulated
      in response to DNA damage are numerous protein biosynthesis genes. Analysis of
      the gene expression data highlighted the essential involvement of sigma(s)
      regulated genes and the general stress response network in the response to DNA
      damage.

PMID- 11967072
TI  - A two-component regulator induces the transmission phenotype of stationary-phase
      Legionella pneumophila.
AB  - Pathogenic Legionella pneumophila evolved as a parasite of aquatic amoebae. To
      persist in the environment, the microbe must be proficient at both replication
      and transmission. In laboratory cultures, as nutrients become scarce a stringent
      response-like pathway coordinates exit from the exponential growth phase with
      induction of traits correlated with virulence, including motility. A screen for
      mutants that express the flagellin gene poorly identified five activators of
      virulence: LetA/LetS, a two-component regulator homologous to GacA/GacS of
      Pseudomonas and SirA/BarA of Salmonella; the stationary-phase sigma factor RpoS;
      the flagellar sigma factor FliA; and a new locus, letE. Unlike wild type, post
      exponential-phase letA and letS mutants were not motile, cytotoxic, sodium
      sensitive or proficient at infecting macrophages. L. pneumophila also required
      fliA to become motile, cytotoxic and to infect macrophages efficiently and letE
      to express sodium sensitivity and maximal motility and cytotoxicity. When induced
      to express RelA, all of the strains exited the exponential phase, but only wild
      type converted to the fully virulent form. In contrast, intracellular replication
      was independent of letA, letS, letE or fliA. Together, the data indicate that, as
      the nutrient supply wanes, ppGpp triggers a regulatory cascade mediated by LetA/
      LetS, RpoS, FliA and letE that coordinates differentiation of replicating L.
      pneumophila to a transmissible form.

PMID- 11967073
TI  - An intrinsic control element for translational initiation in class 1 integrons.
AB  - Integrons are genetic elements able to capture anti-biotic resistance and other
      genes and to promote their transcription. Here, we have investigated integron
      dependent translation of an aminoglycoside 6'-N-acetyltransferase gene (aac(6')
      Ib7) inserted at the attI1 site. N-terminal sequencing revealed that translation
      of this gene was initiated at a GTG codon, which is not part of a plausible
      translation initiation region (TIR). A short open reading frame (called ORF-11)
      overlapping the attI1 site was probed by site-directed mutagenesis for its
      contribution to aac(6')-Ib7 translation. When ORF-11 and its TIR were deleted en
      bloc, translational efficiency dropped by over 80%, as determined with an
      acetyltransferase- luciferase fusion product. Invalidation of the ATG start codon
      of ORF-11 or its putative Shine-Dalgarno sequence resulted in a decrease of over
      60%, whereas the decrease was much less pronounced when the amino acid sequence
      of the putative ORF-11-encoded peptide was altered or when the distance between
      ORF-11 and aac(6')-Ib7 was doubled. This demonstrates that aac(6')-Ib7
      translation is dependent upon the translation of ORF-11, but almost certainly not
      upon the corresponding peptide. These results lead us to conclude that an
      intrinsic short ORF present in the 5'-conserved segment of many class 1 integrons
      may substantially enhance expression at the translational level of captured TIR
      deficient anti-biotic resistance genes.

PMID- 11967074
TI  - Expression of mutant alanine tRNAs increases spontaneous mutagenesis in
      Escherichia coli.
AB  - The expression of mutA, an allele of the glycine tRNA gene glyV, can confer a
      novel mutator phenotype that correlates with its ability to promote Asp-->Gly
      mistranslation. Both activities are mediated by a single base change within the
      anticodon such that the mutant tRNA can decode aspartate codons (GAC/U) instead
      of the normal glycine codons (GCC/U). Here, we investigate whether specific Asp-
      >Gly mistranslation is required for the unexpected mutator phenotype. To address
      this question, we created and expressed 18 individual alleles of alaV, the gene
      encoding an alanine tRNA, in which the alanine anticodon was replaced with those
      specifying other amino acids such that the mutant (alaVX) tRNAs are expected to
      potentiate X-->Ala mistranslation, where X is one of the other amino acids.
      Almost all alaVX alleles proved to be mutators in an assay that measured the
      frequency of rifampicin-resistant mutants, with one allele (alaVGlu) being a
      stronger mutator than mutA. The alaVGlu mutator phenotype resembles that of mutA
      in mutational specificity (predominantly transversions), as well as SOS
      independence, but in a puzzling twist differs from mutA in that it does not
      require a functional recA gene. Our results suggest that general mistranslation
      (as opposed to Asp-->Gly alone) can induce a mutator phenotype. Furthermore,
      these findings predict that a large number of conditions that increase
      translational errors, such as genetic defects in the translational apparatus, as
      well as environmental and physiological stimuli (such as amino acid starvation or
      exposure to antibiotics) are likely to activate a mutator response. Thus, both
      genetic and epigenetic mechanisms can accelerate the acquisition of mutations.

PMID- 11967075
TI  - The roles of the polytopic membrane proteins NarK, NarU and NirC in Escherichia
      coli K-12: two nitrate and three nitrite transporters.
AB  - Two polytopic membrane proteins, NarK and NarU, are assumed to transport nitrite
      out of the Escherichia coli cytoplasm, but how nitrate enters enteric bacteria is
      unknown. We report the construction and use of four isogenic strains that lack
      nitrate reductase Z and the periplasmic nitrate reductase, but express all
      combinations of narK and narU. The active site of the only functional nitrate
      reductase, nitrate reductase A, is located in the cytoplasm, so nitrate reduction
      by these four strains is totally dependent upon a mechanism for importing
      nitrate. These strains were exploited to determine the roles of NarK and NarU in
      both nitrate and nitrite transport. Single mutants that lack either NarK or NarU
      were competent for nitrate-dependent anaerobic growth on a non-fermentable carbon
      source, glycerol. They transported and reduced nitrate almost as rapidly as the
      parental strain. In contrast, the narK-narU double mutant was defective in
      nitrate-dependent growth unless nitrate transport was facilitated by the nitrate
      ionophore, reduced benzyl viologen (BV). It was also unable to catalyse nitrate
      reduction in the presence of physiological electron donors. Synthesis of active
      nitrate reductase A and the cytoplasmic, NADH-dependent nitrite reductase were
      unaffected by the narK and narU mutations. The rate of nitrite reduction
      catalysed by the cytoplasmic, NADH-dependent nitrite reductase by the double
      mutant was almost as rapid as that of the NarK+-NarU+ strain, indicating that
      there is a mechanism for nitrite uptake by E. coli that is in-dependent of either
      NarK or NarU. The nir operon encodes a soluble, cytoplasmic nitrite reductase
      that catalyses NADH-dependent reduction of nitrite to ammonia. One additional
      component that contributes to nitrite uptake was shown to be NirC, the
      hydrophobic product of the third gene of the nir operon, which is predicted to be
      a polytopic membrane protein with six membrane-spanning helices. Deletion of both
      NarK and NirC decreased nitrite uptake and reduction to a basal rate that was
      fully restored by a single chromosomal copy of either narK or nirC. A multicopy
      plasmid encoding NarU complemented a narK mutation for nitrite excretion, but not
      for nitrite uptake. We conclude that, in contrast to NirC, which transports only
      nitrite, NarK and NarU provide alternative mechanisms for both nitrate and
      nitrite transport. However, NarU might selectively promote nitrite ex-cretion,
      not nitrite uptake.

PMID- 11967076
TI  - Two domains of a dual-function NarK protein are required for nitrate uptake, the
      first step of denitrification in Paracoccus pantotrophus.
AB  - Uptake of nitrate into the cytoplasm is the first but least well understood step
      of denitrification; no gene has previously been identified to be necessary for
      this process. Upstream from the structural genes of the membrane-bound nitrate
      reductase (narGHJI) in Paracoccus pantotrophus there is a fusion of two genes,
      each homologous to members of the narK family. The single open reading frame is
      predicted to encode 24 transmembrane helices, comprising two domains, NarK1 and
      NarK2. Analysis of both the accumulation of intracellular nitrite and electron
      transport through the nitrate reductase enzyme in narK mutants reveals that NarK1
      and NarK2 are both involved in nitrate uptake. Maximal rate of nitrate transport
      via NarK2 was dependent upon nitrite, indicating that NarK2 encodes a
      nitrate/nitrite antiporter. The uncouplers S13 and dinitrophenol showed that
      NarK2 was not dependent on the proton motive force for maximal nitrate transport
      activity. Nitrate transport via NarK1 was dependent on proton motive force,
      indicating that it is likely to be a nitrate/proton symporter. Low expression of
      membrane-bound nitrate reductase in narK mutants was counteracted by azide, which
      induced nitrate reductase expression only if the transcriptional activator NarR
      was present.

PMID- 11967077
TI  - The luxS gene is involved in cell-cell signalling for toxin production in
      Clostridium perfringens.
AB  - A Gram-positive anaerobic pathogen, Clostridium perfringens, causes clostridial
      myonecrosis or gas gangrene in humans by producing numerous extracellular toxins
      and enzymes that act in concert to degrade host tissues. C. perfringens possesses
      a homologue of the luxS gene that is reported to be responsible for the
      production of autoinducer 2 (AI-2), which participates in quorum sensing in
      bacteria. The luxS mutant was constructed using C. perfringens strain 13, and the
      role of the luxS gene in toxin production was examined. The cell-free culture
      supernatant from wild-type strain 13 greatly stimulated the luminescence of
      Vibrio harveyi BB170, whereas that from the luxS mutant caused no significant
      stimulation, indicating that the luxS gene is necessary for AI-2 production in C.
      perfringens. The luxS mutant showed a reduced level of production of alpha-,
      kappa- and theta-toxins. In the luxS mutant, the transcription of the theta-toxin
      gene (pfoA) was lower at mid-exponential growth phase, whereas alpha- and kappa
      toxin gene transcription was not significantly affected. The production of toxins
      in the luxS mutant was stimulated by the addition of the culture supernatant from
      the wild-type cells, possibly because of the presence of AI-2. Moreover, the
      expression of the pfoA gene in the luxS mutant was apparently activated when the
      mutant cells were cultured in the presence of culture supernatants from the wild
      type C. perfringens, Escherichia coli DH5alpha carrying the luxS gene of C.
      perfringens. A deletion analysis of the luxS operon showed that the luxS gene
      alone is responsible for cell-cell signalling, and that the metB or cysK genes
      located upstream of luxS are not involved in regulating toxin production. Our
      results indicate that cell-cell signalling by AI-2 plays an important role in the
      regulation of toxin production in C. perfringens.

PMID- 11967078
TI  - The transcription termination factor Rho is required for oxidative stress
      survival in Caulobacter crescentus.
AB  - A transposon Tn5 mutagenesis library was generated from Caulobacter crescentus
      strain NA1000, and clones with deficiency in survival in a high concentration of
      NaCl were selected. One of these clones, 37G10, has the Tn5 integrated within the
      coding region of the transcription termination factor Rho. Analysis of this
      mutant phenotype showed that the cells are motile and present a normal cell
      cycle, but have a longer generation time. This strain is sensitive to acidic pH,
      to the presence of different salts and to heat shock, but it responds well to UV
      light and alkaline pH. The most striking phenotype of the rho mutant is that it
      is extremely sensitive to oxidative stress, in both exponential and stationary
      phases. Experiments using a transcriptional fusion of the rho promoter region to
      the lacZ gene showed that rho gene expression varies during the cell cycle,
      showing very low expression levels at the swarmer cell stage and presenting
      maximum levels in early predivisional cells. Transcription of the rho gene is
      increased in the rho mutant strain, which is indicative of an autoregulatory
      circuit, and there is a small variation in the cell cycle pattern of expression.
      Several peptides have their synthesis altered in the mutant strain, as analysed
      by two-dimensional gel electrophoresis, most of which show a reduction in
      expression. These results indicate that the Rho factor is essential for an
      efficient response to certain stresses in Caulobacter.

PMID- 11967079
TI  - Methylation at nucleotide G745 or G748 in 23S rRNA distinguishes Gram-negative
      from Gram-positive bacteria.
AB  - Bacteria tune the function of their ribosomes by methylating specific rRNA
      nucleotides. Nucleotide G745 in Escherichia coli 23S rRNA is methylated by the
      methyltransferase enzyme RrmA, whereas in Streptomyces fradiae, the neighbouring
      nucleotide G748 is methylated by the enzyme TlrB. Both nucleotides line the
      peptide exit channel of the ribosome at the binding site of macrolide,
      lincosamide and streptogramin B antibiotics. Resistance to the macrolide tylosin,
      which is produced by S. fradiae, is conferred by methylation of G748. RrmA and
      TlrB are homologues (29% identical), and a database search against all presently
      available sequences revealed a further two dozen homologues from a wide variety
      of Bacteria. No homologues were found among the Archaea or Eukarya. The bacterial
      sequences adhere to the species phylogeny and segregate into two groups, in which
      the Gram-negative sequences align with RrmA and the Gram-positives with TlrB.
      Consistently, in more than 20 species tested, the distribution of methylation in
      the Gram-negative rRNAs (methylated at G745) and the Gram-positives (methylated
      at G748) perfectly matches the bacterial phylogeny. Cloning and expression of
      representative methyltransferase genes showed that this specificity of
      methylation is determined solely by the methyltransferase enzyme and is
      independent of the origin of the rRNA substrate. This is the first case in which
      the position of an RNA methylation defines a sharp division between the Gram
      negative and Gram-positive bacteria. Given the specificities and distribution of
      these methyltransferases, we propose a change in the nomenclature of RrmA to
      RlmAI (rRNA large subunit methyltransferase) and of TlrB to RlmAII.

PMID- 11967080
TI  - Selective expression of the beta-subunit of nucleoid-associated protein HU during
      cold shock in Escherichia coli.
AB  - Expression of Escherichia coli hupA and hupB, the structural genes encoding the
      most abundant nucleoid-associated proteins HUalpha and HUbeta has been studied
      during cold shock. This article demonstrates that: (i) transcriptional expression
      of hupA is blocked following a sudden temperature downshift (from 37 degrees C to
      10 degrees C), whereas transcription of hupB from the P2 and P3 promoters is
      maintained at a constitutive level and is activated de novo from the P4 promoter;
      (ii) all three hupB mRNAs (transcribed from the three natural promoters P2, P3
      and P4) become much more stable than the single hupA transcript; and (iii) the
      hupB transcripts, unlike that of hupA, are efficiently translated in vivo during
      cold acclimation and can be actively translated in vitro at low temperature.
      Taken together, the results indicate that during cold shock the expression of the
      HUbeta subunit is preferentially stimulated and that of HUalpha repressed,
      suggesting that an altered HUalpha to HUbeta expression ratio resulting in an
      increase of HUalpha/HUbeta heterodimers and/or (HUbeta)2 homodimers may play an
      important role during cold adaptation.

PMID- 11967081
TI  - Expression of the ExeAB complex of Aeromonas hydrophila is required for the
      localization and assembly of the ExeD secretion port multimer.
AB  - Aeromonas hydrophila secretes protein toxins via the type II pathway, involving
      the products of at least two operons, exeAB (gspAB) and exeC-N (gspC-N). In the
      studies reported here, aerolysin secretion was restored to C5.84, an exeA::Tn5
      751 mutant, by overexpression of exeD alone in trans. Expression studies
      indicated that these results did not reflect a role of ExeAB in the regulation of
      the exeC-N operon. Instead, immunoblot analysis showed that ExeD did not
      multimerize in C5.84, and fractionation of the membranes showed that the
      monomeric ExeD remained in the inner membrane. Expression of ExeAB, but not
      either protein alone, from a plasmid in C5.84 resulted in increases in the amount
      of multimeric ExeD, which correlated with increases in aerolysin secretion. Pulse
      chase analysis also suggested that the induction of ExeAB allowed multimerization
      of previously accumulated monomer ExeD. In C5.84 cells overproducing ExeD, it
      multimerized even in the absence of ExeAB and, although most remained in the
      inner membrane, an amount similar to that in wild-type outer membranes
      fractionated with the outer membrane of the overproducing cells. These results
      indicate that the secretion defect of exeAB mutants is a result of an inability
      to assemble the ExeD secretin in the outer membrane. The localization and
      multimerization of overproduced ExeD in these mutants further suggests that the
      ExeAB complex plays either a direct or indirect role in the transport of ExeD
      into the outer membrane.

PMID- 11967082
TI  - Functional assembly of the foreign carotenoid lycopene into the photosynthetic
      apparatus of Rhodobacter sphaeroides, achieved by replacement of the native 3
      step phytoene desaturase with its 4-step counterpart from Erwinia herbicola.
AB  - Photosynthetic organisms synthesize a diverse range of carotenoids. These
      pigments are important for the assembly, function and stability of photosynthetic
      pigment-protein complexes, and they are used to quench harmful radicals. The
      photosynthetic bacterium Rhodobacter sphaeroides was used as a model system to
      explore the origin of carotenoid diversity. Replacing the native 3-step phytoene
      desaturase (CrtI) with the 4-step enzyme from Erwinia herbicola results in
      significant flux down the spirilloxanthin pathway for the first time in Rb.
      sphaeroides. In Rb. sphaeroides, the completion of four desaturations to lycopene
      by the Erwinia CrtI appears to require the absence of CrtC and, in a crtC
      background, even the native 3-step enzyme can synthesize a significant amount
      (13%) of lycopene, in addition to the expected neurosporene. We suggest that the
      CrtC hydroxylase can intervene in the sequence of reactions catalyzed by phytoene
      desaturase. We investigated the properties of the lycopene-synthesizing strain of
      Rb. sphaeroides. In the LH2 light-harvesting complex, lycopene transfers absorbed
      light energy to the bacteriochlorophylls with an efficiency of 54%, which
      compares favourably with other LH2 complexes that contain carotenoids with 11
      conjugated double bonds. Thus, lycopene can join the assembly pathway for
      photosynthetic complexes in Rb. sphaeroides, and can perform its role as an
      energy donor to bacteriochlorophylls.

PMID- 11967083
TI  - Roles of NapF, NapG and NapH, subunits of the Escherichia coli periplasmic
      nitrate reductase, in ubiquinol oxidation.
AB  - The nap operon of Escherichia coli K-12, encoding a periplasmic nitrate reductase
      (Nap), encodes seven proteins. The catalytic complex in the periplasm, NapA-NapB,
      is assumed to receive electrons from the quinol pool via the membrane-bound
      cytochrome NapC. Like NapA, B and C, a fourth polypeptide, NapD, is also
      essential for Nap activity. However, none of the remaining three polypeptides,
      NapF, G and H, which are predicted to encode non-haem, iron-sulphur proteins, are
      essential for Nap activity, and their function is currently unknown. The relative
      rates of growth and electron transfer from physiological substrates to Nap have
      been investigated using strains defective in the two membrane-bound nitrate
      reductases, and also defective in either ubiquinone or menaquinone biosynthesis.
      The data reveal that Nap is coupled more effectively to menaquinol oxidation than
      to ubiquinol oxidation. Conversely, parallel experiments with a second set of
      mutants revealed that nitrate reductase A couples more effectively with ubiquinol
      than with menaquinol. Three further sets of strains were constructed with
      combinations of in frame deletions of ubiCA, menBC, napC, napF and napGH genes.
      NapF, NapG and NapH were shown to play no role in electron transfer from
      menaquinol to the NapAB complex but, in the Ubi+Men- background, deletion of
      napF, napGH or napFGH all resulted in total loss of nitrate-dependent growth.
      Electron transfer from ubiquinol to NapAB was totally dependent upon NapGH, but
      not on NapF. NapC was essential for electron transfer from both ubiquinol and
      menaquinol to NapAB. The results clearly established that NapG and H, but not
      NapF, are essential for electron transfer from ubiquinol to NapAB. The decreased
      yield of biomass resulting from loss of NapF in a Ubi+Men+ strain implicates NapF
      in an energy- conserving role coupled to the oxidation of ubiquinol. We propose
      that NapG and H form an energy- conserving quinol dehydrogenase functioning as
      either components of a proton pump or in a Q cycle, as electrons are transferred
      from ubiquinol to NapC.

PMID- 11967084
TI  - NAD+-glycohydrolase acts as an intracellular toxin to enhance the extracellular
      survival of group A streptococci.
AB  - Group A streptococci (GAS) produce several secreted products that are thought to
      enhance pathogenicity by facilitating spread of the organisms through host
      tissues. Two such products, streptolysin O (SLO) and NAD+-glycohydrolase, appear
      to be functionally linked, in that SLO is required for transfer of NAD+
      glycohydrolase into epithelial cells. However, the effects of NAD+-glycohydrolase
      on host cells are largely unexplored. We now report that SLO-mediated delivery of
      NAD+-glycohydrolase to the cytoplasm of human keratinocytes results in major
      changes in host cell biology that enhance GAS pathogenicity. We derived isogenic
      mutant strains deficient in the expression of SLO, NAD+-glycohydrolase or both
      proteins in the background of a virulent, M-type 3 strain of GAS. All three
      mutant strains were internalized by human keratinocytes more rapidly and in
      higher numbers than were organisms from the wild-type strain. Association of the
      mutant strains with keratinocytes also resulted in reduced cytotoxicity and
      reduced keratinocyte apoptosis compared with wild-type GAS. These results support
      a model in which NAD+-glycohydrolase contributes to GAS pathogenesis by
      modulating host cell signalling pathways to inhibit GAS internalization, to
      augment SLO-mediated cytotoxicity and to induce keratinocyte apoptosis. We
      conclude that NAD+-glycohydrolase is a novel type of bacterial toxin that acts
      intracellularly in the infected host to enhance the survival and proliferation of
      an extracellular pathogen.

PMID- 11967085
TI  - Quantification of known components of the Escherichia coli TonB energy
      transduction system: TonB, ExbB, ExbD and FepA.
AB  - The TonB-dependent energy transduction system couples cytoplasmic membrane proton
      motive force to active transport of iron-siderophore complexes across the outer
      membrane in Gram-negative bacteria. In Escherichia coli, the primary players
      known in this process to date are: FepA, the TonB-gated transporter for the
      siderophore enterochelin; TonB, the energy-transducing protein; and two
      cytoplasmic membrane proteins with less defined roles, ExbB and ExbD. In this
      study, we report the per cell numbers of TonB, ExbB, ExbD and FepA for cells
      grown under iron-replete and iron-limited conditions. Under iron-replete
      conditions, TonB and FepA were present at 335 +/- 78 and 504 +/- 165 copies per
      cell respectively. ExbB and ExbD, despite being encoded from the same operon,
      were not equimolar, being present at 2463 +/- 522 and 741 +/- 105 copies
      respectively. The ratio of these proteins was calculated at one TonB:two
      ExbD:seven ExbB under all four growth conditions tested. In contrast, the
      TonB:FepA ratio varied with iron status and according to the method used for iron
      limitation. Differences in the method of iron limitation also resulted in
      significant differences in cell size, skewing the per cell copy numbers for all
      proteins.

PMID- 11967086
TI  - HF2: a double-stranded DNA tailed haloarchaeal virus with a mosaic genome.
AB  - HF2 is a haloarchaeal virus infecting two Halorubrum species (Family
      Halobacteriaceae). It is lytic, has a head-and-tail morphology and belongs to the
      Myoviridae (contractile tails). The linear double-stranded DNA genome was
      sequenced and found to be 77 670 bp in length, with a mol% G+C of 55.8. A total
      of 121 likely open reading frames (ORFs) were identified, of which 37 overlapped
      at start and stop codons. The predicted proteins were usually acidic (average pI
      of 4.8), and less than about 12% of them had homologues in the sequence
      databases. Four complete tRNA-like sequences (tRNA-Arg, -Asx, -Pro and -Tyr) and
      an incomplete tRNA-Thr were detected. A transcription map showed that most of the
      genome was transcribed and that the synthesis of transcripts occurred in a highly
      organized and reproducible pattern over a 5 h infection cycle. Transcripts often
      spanned multiple ORFs, suggesting that viral genes were organized into operons.
      The predicted ORF and observed transcript directions matched well and showed that
      transcription is mainly directed inwards from the genome termini, meeting at
      about 45-48 kb, and this was also a turning point in a cumulative GC-skew plot.
      The low point in cumulative GC-skew, near the left end, was a region rich in
      short repeats and lacking ORFs, which is likely to be an origin of replication.
      The HF2 genome is a mosaic of components from widely different sources,
      demonstrating clearly that viruses of haloarchaea, like their bacteriophage
      counterparts, are vectors for the exchange and transmission of genetic material
      between wide taxonomic distances, even across domains.

PMID- 11967088
TI  - Early stages of seed development in Brassica napus: a seed coat-specific cysteine
      proteinase associated with programmed cell death of the inner integument.
AB  - A maternal plant exquisitely promotes the success of its offspring by
      orchestrating embryo development and endowing protection even after the embryos
      mature. It uses ovule integuments for physical and physiological contact with the
      developing embryo and for subsequently equipping the seed with a seed coat
      (testa). The testa is developmentally and metabolically dynamic, but its
      molecular biology is not well understood. We show here that the inner integument
      in Brassica napus undergoes organized development and then programmed cell death
      (PCD), as evident from vacuolation, starch mobilization, DNA fragmentation and
      eventual compression. We have identified a cysteine proteinase gene (BnCysP1)
      that is expressed only in the inner integument as it undergoes PCD, well before
      the embryo begins storage protein synthesis. Two paralogous Cys proteinases have
      been recruited in rapeseed for the PCD of testa and for leaf senescence, and
      these differ 25% in their primary structure and post-translational modifications.
      Despite Arabidopsis being closely related to rapeseed, and an indication of
      developmental compression of its inner integument, the Arabidopsis genome is
      suggestive of only one Cys proteinase that shows approximately 72% identity to
      BnCysP1. It is, however, leaf senescence-associated, and the other Cys
      proteinases are <52% identical. BnCysP1 also differs from ricinosome-deployed PCD
      Cys endopeptidases in lacking the hallmark KDEL tail and being glycosylated.
      BnCysP1, one of the very few plant genes known to function only in the seed coat,
      will be useful in dissecting post-fertilization development of this important
      organ in rapeseed.

PMID- 11967089
TI  - Gene transfer from mitochondrion to nucleus: novel mechanisms for gene activation
      from Cox2.
AB  - The evolutionarily recent transfer of the gene for cytochrome c oxidase subunit 2
      (cox2) from the mitochondrion to the nucleus in legumes is shown to have involved
      novel gene-activation steps. The acquired mitochondrial targeting presequence is
      bordered by two introns. Characterization of the import of soybean Cox2 indicates
      that the presequence is cleaved in a three-step process which is independent of
      assembly. The final processing step takes place only in the mitochondria of
      legume species, and not in several non-legume plants. The unusually long
      presequence of 136 amino acids consists of three regions: the first 20 amino
      acids are required for mitochondrial targeting and can be replaced by another
      presequence; the central portion of the presequence is required for efficient
      import of the Cox2 protein into mitochondria; and the last 12 amino acids,
      derived from the mitochondrially encoded protein, are required for correct
      maturation of the imported protein. The acquisition of a unique presequence, and
      the capacity for legume mitochondria to remove this presequence post-import, are
      considered to be essential adaptations for targeting of Cox2 to the mitochondrion
      and therefore activation of the transferred gene in the nucleus.

PMID- 11967090
TI  - AtMYB21, a gene encoding a flower-specific transcription factor, is regulated by
      COP1.
AB  - Light is an important environmental signal that governs plant growth and
      development. One important light-signalling component involved in plant light
      responses is COP1. The pleiotropic phenotypes of the cop1 mutant suggest that
      COP1 regulates not only photomorphogenesis, but also other developmental
      processes. We investigated the role of COP1 by identifying genes that are
      regulated by COP1. We report that AtMYB21, a gene encoding a flower-specific
      transcription factor, is ectopically expressed in the cop1 mutant. Analysis shows
      that dark-grown transgenic seedlings expressing AtMYB21-GR fusion protein display
      some features of the cop1 mutant, including decreased hypocotyl cell expansion,
      open cotyledons in the dark, and seedling lethality in the presence of
      dexamethasone. Light-grown adult transgenic plants expressing AtMYB21 have
      shorter stems, smaller and narrower leaves, narrower petals, and malformed
      carpels. In addition, we show that AtMYB21 directly regulates two genes that are
      also expressed more abundantly in the cop1 mutant. The results indicate that COP1
      is required to repress the AtMYB21 gene in seedlings, and the pleiotropic
      phenotypes shown in the cop1 mutant are due to the combination of misregulation
      of genuine light-signalling components and other tissue-specific factors.

PMID- 11967091
TI  - The Arabidopsis REF8 gene encodes the 3-hydroxylase of phenylpropanoid
      metabolism.
AB  - The activity of p-coumarate 3-hydroxylase (C3H) is thought to be essential for
      the biosynthesis of lignin and many other phenylpropanoid pathway products in
      plants; however, no conditions suitable for the unambiguous assay of the enzyme
      are known. As a result, all attempts to purify the protein and clone its
      corresponding gene have failed. By screening for plants that accumulate reduced
      levels of soluble fluorescent phenylpropanoid secondary metabolites, we have
      identified a number of Arabidopsis mutants that display a reduced epidermal
      fluorescence (ref) phenotype. Using radiotracer-feeding experiments, we have
      determined that the ref8 mutant is unable to synthesize caffeic acid, suggesting
      that the mutant is defective in a gene required for the activity or expression of
      C3H. We have isolated the REF8 gene using positional cloning methods, and have
      verified that it encodes C3H by expression of the wild-type gene in yeast.
      Although many previous reports in the literature have suggested that C3H is a
      phenolase, the isolation of the REF8 gene demonstrates that the enzyme is
      actually a cytochrome P450-dependent monooxygenase. Although the enzyme accepts p
      coumarate as a substrate, it also exhibits significant activity towards other p
      hydroxylated substrates. These data may explain the previous difficulties in
      identifying C3H activity in plant extracts and they indicate that the currently
      accepted version of the lignin biosynthetic pathway is likely to be incorrect.

PMID- 11967092
TI  - Changes in secondary metabolism and deposition of an unusual lignin in the ref8
      mutant of Arabidopsis.
AB  - The end products of the phenylpropanoid pathway play important roles in plant
      structure and development, as well as in plant defense mechanisms against biotic
      and abiotic stresses. From a human perspective, phenylpropanoid pathway-derived
      metabolites influence both human health and the potential utility of plants in
      agricultural contexts. The last known enzyme of the phenylpropanoid pathway that
      has not been characterized is p-coumarate 3-hydroxylase (C3H). By screening for
      plants that fail to accumulate soluble fluorescent phenylpropanoid secondary
      metabolites, we have identified a number of Arabidopsis mutants that display a
      reduced epidermal fluorescence (ref) phenotype. We have now shown that the ref8
      mutant is defective in the gene encoding C3H. Phenotypic characterization of the
      ref8 mutant has revealed that the lack of C3H activity in the mutant leads to
      diverse changes in phenylpropanoid metabolism. The ref8 mutant accumulates p
      coumarate esters in place of the sinapoylmalate found in wild-type plants. The
      mutant also deposits a lignin formed primarily from p-coumaryl alcohol, a monomer
      that is at best a minor component in the lignin of other plants. Finally, the
      mutant displays developmental defects and is subject to fungal attack, suggesting
      that phenylpropanoid pathway products downstream of REF8 may be required for
      normal plant development and disease resistance.

PMID- 11967093
TI  - The Arabidopsis gain-of-function mutant dll1 spontaneously develops lesions
      mimicking cell death associated with disease.
AB  - We describe the characterization of a novel gain-of-function Arabidopsis mutant,
      dll1 (disease-like lesions1), which spontaneously develops lesions mimicking
      bacterial speck disease and constitutively expresses biochemical and molecular
      markers associated with pathogen infection. Despite the constitutive expression
      of defense-related responses, dll1 is unable to suppress the growth of virulent
      pathogens. However, dll1 elicits normal hypersensitive response in response to
      avirulent pathogens, thus indicating that dll1 is not defective in the induction
      of normal resistance responses. The lesion+ leaves of dll1 support the growth of
      hrcC mutant of Pseudomonas syringae, which is defective in the transfer of
      virulence factors into the plant cells, and therefore non-pathogenic to wild-type
      Col-0 plants. This suggests that dll1 intrinsically expresses many of the
      cellular processes that are required for pathogen growth during disease.
      Epistasis analyses reveal that salicylic acid and NPR1 are required for lesion
      formation, while ethylene modulates lesion development in dll1, suggesting that
      significant overlap exist between the signalling pathways leading to resistance-
      and disease-associated cell death. Our results suggest that host cell death
      during compatible interactions, at least in part, is genetically controlled by
      the plant and DLL1 may positively regulate this process.

PMID- 11967094
TI  - The water permeability of Arabidopsis plasma membrane is regulated by divalent
      cations and pH.
AB  - Mechanisms that regulate water channels in the plant plasma membrane (PM) were
      investigated in Arabidopsis suspension cells. Cell hydraulic conductivity was
      measured with a cell pressure probe and was reduced 4-fold as compared to control
      values when calcium was added in the pipette and in bathing solution. To assess
      the significance of these effects in vitro, PM vesicles were isolated by aqueous
      two-phase partitioning and their water transport properties were characterized by
      stopped-flow spectrophotometry. Membrane vesicles isolated in standard conditions
      exhibited reduced water permeability (P(f)) together with a lack of active water
      channels. In contrast, when prepared in the presence of chelators of divalent
      cations, PM vesicles showed a 2.3-fold higher P(f) and active water channels.
      Furthermore, equilibration of purified PM vesicles with divalent cations reduced
      their P(f ) and water channel activity down to the basal level of membranes
      isolated in standard conditions. Ca2+ was the most efficient with a half
      inhibition of P(f) at 50-100 microM free Ca2+. Water transport in purified PM
      vesicles was also reversibly blocked by H+, with a half-inhibition of P(f )at pH
      7.2-7.5. Thus, both Ca2+ and H+ contribute to a membrane-delimited switch from
      active to inactive water channels that may allow coupling of water transport to
      cell signalling and metabolism.

PMID- 11967095
TI  - cDNA microarray analysis of gene expression during Fe-deficiency stress in barley
      suggests that polar transport of vesicles is implicated in phytosiderophore
      secretion in Fe-deficient barley roots.
AB  - To acquire Fe from soil, graminaceous plants secrete mugineic acid family
      phytosiderophores (MAs) from their roots. The secretion of MAs increases in
      response to Fe deficiency, and shows a distinct diurnal rhythm. We used a
      microarray that included 8987 cDNAs of rice EST clones to examine gene expression
      profiles in barley roots during Fe-deficiency stress. Approximately 200 clones
      were identified as Fe-deficiency-inducible genes, of which seven had been
      identified previously. In order to meet the increased demand for methionine to
      produce MAs, Fe-deficiency enhances the expression of genes that participate in
      methionine synthesis, as well as recycling methionine through the Yang cycle. Of
      these 200 genes, approximately 50 exhibited different transcription levels in Fe
      deficient roots at noon and at night. Northern blot analysis of time course
      experiments confirmed that five of these genes exhibited a diurnal change in
      their level of expression. The diurnal changes in the expression of these genes
      suggest that polar vesicle transport is involved in the diurnal secretion of MAs.

PMID- 11967096
TI  - A role for nitrilase 3 in the regulation of root morphology in sulphur-starving
      Arabidopsis thaliana.
AB  - Arabidopsis thaliana expresses four nitrilases, three of which (NIT1, NIT2 and
      NIT3) are able to convert indole-3-acetonitrile to indole-3-acetic acid (IAA),
      the plant growth hormone, while the isozyme NIT4 is a beta-cyano-l-alanine
      hydratase/nitrilase. NIT3 promoter activity is marginal in leaves or roots of
      vegetative plants and undetectable in bolting and flowering plants, but its level
      increases strongly when plants experience sulphur deprivation. No other nitrilase
      genes respond to sulphur supply/deficiency. Neither N- nor P-deprivation cause
      detectable changes in NIT3 promoter activity. In transgenic plants expressing
      uidA under the control of the NIT3 promoter (NIT3p::uidA), sulphate deprivation
      leads to the appearance of beta-glucuronidase activity in shoots and particularly
      in roots, most strongly in the conductive tissues and lateral root primordia.
      Deletion analysis allowed localization of the sulphur-responsive element to a 317
      bp segment of the NIT3 promoter encompassing nt -2151 to -1834 upstream of the
      transcriptional start point. Both nitrilase polypeptide and nitrilase activity
      were also induced by sulphur starvation. NIT3 promoter activity was strongly
      induced by O-acetylserine, suggesting that, as is the case with enzymes of
      sulphate assimilation, sulphate deficiency may be communicated to NIT3 via an
      increase in the level of the cysteine precursor, O-acetylserine. During sulphur
      deprivation, a preferential depletion of the pool of the indole-3-acetonitrile
      precursor glucobrassicin compared with that of total glucosinolates was noticed.
      In the absence of an external sulphate supply, plants developed longer roots with
      a higher number of lateral roots. The increased growth of the root system
      occurred at the expense of shoot growth which was retarded under conditions of
      sulphur starvation. Taken together, these results suggest that a regulatory loop
      appears to exist by which sulphate deficiency, through an increase in
      glucobrassicin turnover and nitrilase 3 accumulation, initiates the production of
      extra auxin leading to increased root growth and branching, thus allowing the
      root system to penetrate new areas of soil effectively to gain access to fresh
      supplies of sulphur.

PMID- 11967098
TI  - Single-step transformation for generating marker-free transgenic rice using the
      ipt-type MAT vector system.
AB  - The ipt-type MAT vector uses the ipt gene for regeneration of marker-free
      transgenic plants. However, it was pointed out that this system was not suitable
      for most economically important crops that regenerated through auxin-dependent
      embryogenesis. We report a single-step transformation system of rice using MAT
      vector. When we transformed scutellum tissues of 5 days pre-cultured rice seeds,
      marker-free transgenic rice plants directly regenerated from 25.5% infected
      scutellum tissues without forming ipt-intermediates within 4 weeks after an
      infection. Excision of the ipt gene caused the regeneration of marker-free
      transgenic rice plants through embryogenic tissues. Therefore, this system needs
      no selective agent and no sexual crossing for identification of transgenic plants
      not containing a selectable marker gene. This system is highly effective for
      generation of marker-free transgenic plants in economically important crops.

PMID- 11967097
TI  - Geminivirus-based vectors for gene silencing in Arabidopsis.
AB  - Gene silencing, or RNA interference, is a powerful tool for elucidating gene
      function in Caenorhabditis elegans and Drosophila melanogaster. The vast genetic,
      developmental and sequence information available for Arabidopsis thaliana makes
      this an attractive organism in which to develop reliable gene-silencing tools for
      the plant world. We have developed a system based on the bipartite geminivirus
      cabbage leaf curl virus (CbLCV) that allows silencing of endogenous genes singly
      or in combinations in Arabidopsis. Two vectors were tested: a gene-replacement
      vector derived from the A component; and an insertion vector derived from the B
      component. Extensive silencing was produced in new growth from the A component
      vectors, while only minimal silencing and symptoms were seen in the B component
      vector. Two endogenous genes were silenced simultaneously from the A component
      vector and silencing of the genes was maintained throughout new growth. Because
      the CbLCV vectors are DNA vectors they can be inoculated directly from plasmid
      DNA. Introduction of these vectors into intact plants bypasses transformation and
      extends the kinds of silencing studies that can be carried out in Arabidopsis.

PMID- 11967099
TI  - The importance of maternal mental health during pregnancy: theory, practice, and
      intervention.

PMID- 11967100
TI  - A portrait: Magdalena's dream.
AB  - A recent critical ethnographic study examined the effects of the health care
      system, historical exploitation, socioeconomic factors, and cultural values on
      retired migrant farm workers in northeastern Colorado. Combining ethnographic
      interviews, participant observation, photography, and critical analysis, study
      findings indicated a need to increase the cultural knowledge and collaborative
      efforts of health care providers. Emerging from the study, this article presents
      a creative composite vignette of retired migrant farm workers. The narrative and
      photograph offer testimony to the lived experience of these rural older Hispanic
      persons. The intent of the story is to provide the readers with deepened
      understanding of the hardships, social ostracism, economic challenges, personal
      hardiness, and cultural values that are characteristic of this special
      population.

PMID- 11967101
TI  - Social justice or market justice? The paradoxes of public health partnerships
      with managed care.
AB  - Public health is increasingly joining forces with managed care, yet the effect of
      this partnership on public health nursing (PHN) has received little scrutiny. The
      feasibility and consequences of a public-private alliance raise questions about
      whether the mission of public health can be sustained in a managed care system
      and whether managed care's approaches to health care are conducive to providing
      population-oriented care. Expanding the links between PHN and private
      organizations is both problematic and promising. Managed care organizations have
      much to offer, including coordination of services and comprehensive care.
      However, they may also restrict coverage and create bureaucratic obstacles to
      obtaining services. The growth of for-profit health care corporations evokes
      questions about ways in which concern for communities and populations collide
      with stockholder interests. The task for PHN is to recognize and to dialogue
      about these complexities so that nursing's voice can be heard as solutions to
      these dilemmas are created.

PMID- 11967102
TI  - Midlife and older rural women's adherence to U.S. Dietary Guidelines across
      stages of change in healthy eating.
AB  - Poor diet is one of the factors that influences morbidity and premature mortality
      among older women. The purpose of this descriptive correlational study was to
      assess (a) healthy eating behaviors of midlife and older rural women, as
      reflected by adherence to the Dietary Guidelines for Americans, and (b)
      differences in daily servings in each food group consumed by the women across
      stages of readiness for change in healthy eating. A sample of 371 midlife and
      older rural women attending a national meeting of a community education
      organization completed a questionnaire, including items to measure healthy eating
      and readiness for change in healthy eating. Only 5.9% of the women adhered to all
      levels of the Food Pyramid. Adherence to individual levels ranged from 3.5% for
      grain products to 65.4% for fruit. Analyses of variance revealed significant
      differences (p < 0.05) in servings consumed daily across stages of change for
      grain (F=4.80), fruits (F=19.02), vegetables (F=9.24), dairy (F=2.45), and meats
      (F=1.98). Findings suggest the need for community health nurses to design dietary
      interventions tailored for women's stage of readiness for change to reduce
      disability in this vulnerable population.

PMID- 11967103
TI  - A program to prevent iron poisoning using public health nurses in a county health
      department.
AB  - Despite 50 years of educational and legislative efforts aimed at increasing
      public awareness of the toxicity of iron, it remains a leading cause of poisoning
      death in children. The purpose of this study was to educate public health nurses
      (PHNs) on the prevention of iron poisoning utilizing, a "Train the Trainer"
      design. Educational programs were based on cognitive and behavioral approaches
      and consisted of a pretest, lecture, posttest, and evaluation. In addition, a
      follow-up survey was conducted at 8-months posttraining in order to determine the
      application of iron poison-prevention principles. Prior to the program, 71% of
      the PHNs were unable to identify iron as a leading household poison. Sixty
      percent reported storage habits of medication that predispose children to
      poisoning. The overall score on the pretest was 56% compared with the mean
      posttest score of 96%. Of the 45 respondents to the follow-up survey, 87% had
      used the program information to educate patients on the dangers of iron
      poisoning. This iron poison prevention program provided a successful educational
      program for PHNs that was then applied to patient education.

PMID- 11967104
TI  - An information system for community nursing.
AB  - In this article, an information system for community nursing is presented. It is
      critically evaluated on the basis of practical experiences. Its goal is not only
      to reduce the workload with modern information and communication technology but
      also to improve the quality of nurses' work. The quality improved because of the
      process method of work, which led toward a better client/patient orientation and
      more creative and research-oriented nurses' work based on nursing knowledge
      management support. It relies on an integrated and structured information
      picture, with special emphasis on transparency and interpretability.

PMID- 11967105
TI  - Primary health care for Korean immigrants: sustaining a culturally sensitive
      model.
AB  - This report describes a 4-year long bilingual interdisciplinary primary health
      care project that was designed to make culturally sensitive services available to
      underserved Korean immigrants in Chicago. It also describes some of the
      particular needs of this population and the strategies that the project staff
      adopted to identify and address the population's mental health needs. The project
      reflected the successful collaborative efforts of four participating principals:
      the Korean community, the University of Illinois at Chicago College of Nursing,
      the Chicago Department of Public Health, and the W. K. Kellogg Foundation. The
      model of service demonstrated in the project paired a bilingual advanced practice
      nurse, a certified family nurse practitioner, with a bilingual community advocate
      to conduct a program emphasizing community outreach and health promotion and
      prevention. A bilingual physician provided consultation for the nurse and
      attended to patients in need of medical care. Patients were referred to bilingual
      community social service agencies for assistance with a variety of other
      problems. A central goal of the project was for the services developed during its
      course to be assimilated into the regular programming of the Chicago Department
      of Public Health, a goal that was achieved. Finally, some of the challenges of
      introducing role change into an organization are discussed.

PMID- 11967106
TI  - A population-based approach to pediculosis management.
AB  - Pediculosis is a population-based problem that is a priority concern for many
      communities. Public health nurses in a county health department collaborated with
      epidemiologists, nursing students, and faculty to design and implement an
      effective population-based pediculosis management project. The focus of the
      project was the development of pediculosis treatment and prevention guidelines
      based on recognized best practices that were acceptable to both epidemiologists
      and practicing public health nurses. Public health nurses disseminated these
      guidelines to community providers and reinforced their use through consultation
      and educational sessions. Two critical changes occurred as a result of the
      project. First, community providers significantly changed their recommendations
      for the treatment of pediculosis after nursing intervention. Second, public
      health nurses increased their population-based practice skills, continued to use
      those skills to address pediculosis, and extended those skills to additional
      population-based initiatives.

PMID- 11967107
TI  - Mobilizing the community to address the prenatal health needs of Immigrant
      Punjabi women.
AB  - In Canada, although prenatal education is available to all women, there are
      groups who do not access these services. One such group is Immigrant Punjabi
      women residing in the Lower Mainland of British Columbia. It was apparent that
      structured prenatal education, even when translation was available, would not
      meet the needs of this group. Efforts were required to help bring this issue into
      the community so that the community would endorse women's participation in
      prenatal preparation. The purpose of the project described in this article was to
      explore how community mobilization strategies could be used to improve the health
      of pregnant women in the Punjabi community. A collaborative approach was used
      with representatives from a variety of service agencies and the community. The
      mobilization strategy involved creating a platform to communicate with the
      community about prenatal health and health care, creating "buy-in" from the
      physicians serving the women of the community, and providing prenatal sessions
      that built on the existing knowledge of the women. We describe the mobilization
      process and discuss the insights gained.

PMID- 11967108
TI  - The role of social support in the self-management of diabetes mellitus among a
      Hispanic population.
AB  - The rising incidence of diabetes mellitus continues to be a major health concern
      among Hispanic Americans. Social support has been found to be a relevant factor
      in diabetes self-management, however, it has not been explored within a Hispanic
      community. This cross-sectional study was therefore conducted with 95 insulin
      requiring Hispanic adults to explore the composition of the support network, the
      type of assistance needed, the degree of satisfaction with support received, and
      the relationship between social support and diabetes self-management. Overall,
      the participants had fairly large networks, composed primarily of family members.
      The greatest need for assistance was associated with transportation or
      interactions that involved speaking English, and the assistance offered in these
      areas was viewed as highly satisfactory. Participants were least satisfied with
      the help they received for diabetes-related self-care, personal care, and
      financial assistance. Social support was not strongly related to diabetes self
      management. Community health nurses must be aware that this population may have
      needs that are unsatisfactorily met. They should provide education and resources
      for support persons and carefully evaluate the support network, not only for
      availability, but also for satisfaction. Effort should also be directed toward
      developing alternative support for those without available family.

PMID- 11967109
TI  - Determinants of exercise in adults with cerebral palsy.
AB  - This study examined the impact of environmental factors and caregiver attitudes
      on exercise participation in adults with cerebral palsy using a social-cognitive
      model. The sample included 83 adults with cerebral palsy (47.0% males and 53.0%
      females). Hierarchical regression analysis was conducted with exercise frequency
      as the dependent variable. Independent variables included personal
      characteristics of persons with cerebral palsy (age, level of mental retardation,
      health status, mobility, and arm/hand limitation), type of residence, exercise
      facility access, and caregiver-perceived benefits of exercise for people with
      cerebral palsy. The significant determinants of exercise participation were the
      caregiver's perceived benefits of exercise for persons with cerebral palsy and
      the type of residence. When caregivers perceived greater benefits of exercise,
      adults with cerebral palsy were likely to exercise more frequently. Non-nursing
      home residents were more likely to exercise than nursing home residents. This
      difference was related to differences in the caregivers' perceived benefits of
      exercise and not because of the personal characteristics of the residents or
      access to the exercise facility. Results of this study point to the need to
      inform and educate caregivers about the benefits and importance of exercise for
      adults with cerebral palsy.

PMID- 11967111
TI  - To be or Not to be ridded?--That is the question addressed by the associative
      antigen recognition model.
AB  - The reasons that germline-encoded recognitive sites cannot sort the immune
      system's large and random somatically generated repertoire into anti-Not-to-be
      ridded ('self ') and anti-To-be-ridded ('nonself ') specificities are analysed.
      The immune system cannot use 'nonself '-markers of To-be-ridded antigens
      ('Danger', toll receptors, pathogenicity, localization, etc.) to sort the
      repertoire; it may, however, use them to determine the magnitude and class of the
      effector response.

PMID- 11967112
TI  - Ocular toxoplasmosis: more than just what meets the eye.
AB  - Toxoplasma gondii is an intracellular parasite whose life cycle may include the
      man as an intermediate host. Close to a billion people are infected with this
      parasite worldwide. Ocular lesions may occur in up to 25% of those individuals
      infected. The infection may occur intra-uterus, through the placenta when the
      mother is infected during pregnancy. The parasite may also infect adults after
      the ingestion of contaminated food products, most notably meats or water. We have
      shown that although congenital and post-natal (acquired) infection results in
      similar ocular lesions, the immunological mechanisms behind the development of
      disease are different. On the other hand, contrary to published data obtained in
      mice, we were unable to find evidence that the T. gondii express superantigen
      activity for human lymphocytes. Our findings are important because they suggest
      that superantigen activity is not important as a pathological mechanism in human
      disease. Our data also suggest that, whereas the ocular lesion caused by
      infection after birth is the result of an excessive or dysfunctional immune
      response, the lesions caused by congenital infection may be due to a lack of an
      appropriate response to the parasite.

PMID- 11967113
TI  - 'Ignorance' of antigen-specific murine CD4+ and CD8+ T cells is overruled by
      lipopolysaccharide and leads to specific induction of IFN-gamma.
AB  - Lipopolysaccharide (LPS) can activate human and murine T cells in vivo and in
      vitro. Here we analysed the effects of LPS on T cells with defined specificities
      in T-cell receptor (TCR)-transgenic systems. LPS rapidly induced high amounts of
      interferon (IFN)-gamma in a subpopulation of purified T cells from DO11.10
      (OVA323-339/H2-Ad) and OT-1 (OVA257-264/H2-Kb) mice when coincubated with antigen
      pulsed peritoneal exudate cells (PECs). LPS induced IFN-gamma in T cell cultures
      even when the number of antigenic major histocompatibility complex (MHC) class-I
      complexes was too small to stimulate the T cells. LPS, thus, overruled the
      unresponsiveness of the otherwise 'antigen-ignorant' T cells. The release of IFN
      gamma strictly correlates with the PECs' ability to produce interleukin (IL)-12.
      In contrast to the induction of IFN-gamma, antigen-specific IL-2 secretion and
      proliferation of T cells were rather decreased in the presence of LPS. Only very
      few IFN-gamma-secreting natural killer (NK) cells and natural killer T (NKT)
      cells in the given experimental system could be detected using intracellular
      fluorescence-activated cell sorter (FACS) staining. Taken together, our results
      indicate that LPS has the potential to activate quiescent T cells and to
      specifically induce IFN-gamma in CD4 and CD8 T cells. This may have direct
      consequences for the activation of autoreactive T cells following bacterial
      infections.

PMID- 11967114
TI  - Expression of the B cell-attracting chemokine CXCL13 in the target organ and
      autoantibody production in ectopic lymphoid tissue in the chronic inflammatory
      disease Sjogren's syndrome.
AB  - Sjogren's syndrome is an autoimmune disease characterized by lymphocytic
      infiltrates resembling secondary lymphoid organs in salivary glands. In this
      study, we demonstrate the expression of the lymphoid tissue homing chemokine
      CXCL13 (BCA-1/BLC), which has attracting properties for B cells and subsets of
      activated T cells, in salivary glands of patients with Sjogren's syndrome using
      immunohistochemistry and in situ hybridization. CXCL13 expression was primarily
      observed in epithelial cells in acini and ducts of inflamed glands while its
      receptor, CXCR5 (BLR-1), was expressed on the infiltrating mononuclear cells. In
      addition, cells producing antibodies against one of the major autoantigens in
      Sjogren's syndrome, Ro 52, were identified at the periphery of the follicular
      infiltrates indicating that the ectopic lymphoid tissue is directly involved in
      the disease process. Identification of CXCL13 and CXCR5 in salivary glands
      suggests that the target organ plays an essential role in the inflammatory
      process by recruiting B and T cells. These results also provide a molecular
      mechanism by which lymphoid neogenesis and ectopic germinal centre formation
      might occur in the glands of these patients, which may be the key step in the
      development of the chronic inflammatory process in Sjogren's syndrome.

PMID- 11967115
TI  - Expression and function of CD22, a B-cell restricted molecule.
AB  - In this work, we studied the expression and function of CD22 in murine B cells.
      CD22 has been previously characterized as an activation marker of mature B
      lymphocytes. However, we found that CD22 is expressed early during the ontogeny
      of B cells in the bone marrow and spleen, and was found on B cells isolated from
      all the different lymphoid compartments. We also found that B cells stimulated
      through the B-cell antigen receptor (BCR), CD38 and CD40, upregulated CD22
      expression to maximal levels within 24 h after stimulation, but that the levels
      of CD22 declined at later times (48 and 72 h). CD22 is rapidly phosphorylated
      after BCR signal transduction, and is believed to downregulate B-cell activation.
      In this study, we did not detect CD22 phosphorylation in activated B cells after
      CD38 or CD40 cross-linking, even though CD22 was clearly phosphorylated in the
      BCR-stimulated B cells. Consistent with this, we found no evidence of physical
      association between CD38 or CD40 and CD22 in B cells. The lack of association or
      phosphorylation of CD22 induced by CD38 and CD40 cross-linking indicates that
      CD22 may not downregulate the activation induced by these two molecules.

PMID- 11967116
TI  - Haptoglobin interacts with the human mast cell line HMC-1 and inhibits its
      spontaneous proliferation.
AB  - Haptoglobin (Hp) is an acute phase reactant produced by hepatocytes. There is
      evidence for an immunomodulatory potential of Hp, though there is no clear
      evidence yet about the mechanisms of this action. We have previously shown that
      Hp interacts with the beta2-integrin CD11b/CD18. In addition, other investigators
      reported the binding of Hp to B lymphocytes through the CD22 receptor, and to
      neutrophils through two different receptors. In the present study, we
      investigated the interaction of haptoglobin with the human mast cell line HMC-1.
      We report that fluorescein isothiocyanate (FITC)-labelled haptoglobin binds to
      this cell line and that binding is increased by calcium in a dose- and time
      dependent manner. Hp binding sites on HMC-1 were upregulated upon stimulation
      with phorbol myristate acetate (PMA)/A23187 and after treatment with anti-CD43
      and anti-CD44 monoclonal antibodies (MoAbs). HMC-1 cells do not express either
      CD11b/CD18 or CD22 receptors, indicating that the haptoglobin-binding receptor on
      this cell line is different from the known receptors. Assessment of cell function
      showed that Hp inhibits the spontaneous growth of HMC-1 up till 40% at higher Hp
      concentrations, but it did not exhibit any effect on the expression of CD54 on
      the release of either tryptase or IL-1ra. In conclusion, haptoglobin binds
      specifically to human mast cells via a receptor different from CD11b/CD18 and
      CD22, and may play a role in the modulation of mast cell functions. Exploration
      of Hp effects in mast cell-dependent diseases such as allergic rhinitis and
      urticaria seems warranted.

PMID- 11967117
TI  - Induction of oral tolerance with micro-doses of ovomucoid depends on the length
      of the feeding period.
AB  - Oral administration of antigen induces antigen-specific immunologic tolerance,
      which is known to be dose-dependent. We studied the influence of continuous oral
      administration of nanogram and microgram doses of antigen on oral tolerance
      induction. Mice were continuously exposed to varying doses (1 ng-1 mg/day) of
      ovomucoid (OM) for a minimum of 30 days and a maximum of 100 days. It was
      possible to induce oral tolerance measured as reduced proliferation and antibody
      production (immunoglobulin (Ig)G1, IgG2a and total Igs) when mice were fed 1 mg
      of OM/day for 40 or 50 days. It was not possible to induce oral tolerance with
      daily doses of antigen of 10 microg or less. Feeding of 100 microg OM/day for 40
      and 50 days and 1 mg OM/day for 30 days generated tolerization of Th2-dependent
      responses, but retained an intact response of Th1-dependent antibodies, whereas
      feeding of 1 mg OM/day for 40 and 50 days resulted in tolerization of both Th1-
      and Th2-antibody responses. The results presented here suggest that there is a
      threshold of microgram-doses below which oral tolerance cannot be induced, and
      that selective suppression of Th2 responses can be achieved by continuous
      microdose feeding, while an extension of the feeding dose or feeding period
      tolerizes both Th1- and Th2-dependent responses.

PMID- 11967118
TI  - A heat-stable component of Bartonella henselae upregulates intercellular adhesion
      molecule-1 expression on vascular endothelial cells.
AB  - Bartonella henselae upregulated the expression of intercellular adhesion molecule
      1 (ICAM-1) on human umbilical vein endothelial cells (HUVECs). The induction
      level of ICAM-1 depended on the inoculation bacterial dose. ICAM-1 expression
      began increasing 4 h after infection and reached a sustained peak beginning at 12
      h after B. henselae infection; this time course was similar to that of
      lipopolysaccharide (LPS) of Escherichia coli. The stimulatory effect was
      abolished when live B. henselae were separated from HUVECs by a filter membrane.
      The nonpiliated strain, which is unable to invade endothelial cells, induced ICAM
      1 expression to the same extent as the piliated strain. Inactivation of B.
      henselae by ultraviolet (UV) irradiation, heat (56 degrees C, 30 min), or
      sonication did not alter its stimulatory activity. Polymyxin B, which strongly
      inhibited the effect of LPS, did not exert any influence on the stimulatory
      activity of B. henselae. Furthermore, the effect of sonicated B. henselae was not
      inhibited even by boiling, which was also the case with LPS. Our data suggest
      that some heat-stable component of B. henselae binds to the endothelial cell
      surface, inducing ICAM-1 expression. Though the participation of LPS could not be
      completely ruled out, we suppose that some unidentified heat-stable proteins,
      lipids, or polysaccharides may be the stimulatory factor(s). The ability of B.
      henselae to enhance the expression of adhesion molecules on endothelial cells may
      be an important mechanism in the pathogenesis of B. henselae infection.

PMID- 11967119
TI  - Costimulatory molecule requirement for bovine WC1+gammadelta T cells'
      proliferative response to bacterial superantigens.
AB  - We have previously shown that the proliferation of freshly isolated bovine
      WC1+gammadelta T cells to superantigens (SAgs) including staphylococcal
      enterotoxin A (SEA), and staphylococcal enterotoxin B (SEB) or toxic shock
      syndrome type-1 (TSST-1) required the presence of antigen-presenting cells (APC)
      and the addition of exogenous interleukin (IL)-2. The costimulatory activity
      provided by molecules expressed on professional APC for the proliferation of
      gammadelta T cells has not been addressed hitherto. In the present study, we
      investigated the ability of two selected APC populations, the dendritic cells
      (DCs) highly expressing CD80 and CD86 molecules (CD80highCD86high) and the
      monocytes expressing the same molecules at a rather low level (CD80lowCD86low),
      to stimulate the proliferation of purified bovine WC1+gammadelta T cells to SAgs.
      DCs were more efficient than monocytes in inducing gammadelta T-cell
      proliferation, and this response was dependent on exogenous IL-2 in both
      presentation modes. Stimulating gammadelta T cells with gradual doses of SAgs or
      concanavalin A (ConA) resulted in similar dose-dependent reaction profiles
      suggesting a minimal role of the major histocompatibility complex (MHC). However,
      significant proliferation was already obtained with the starting doses in the
      presence of DC compared with monocytes, and higher proliferation was reached with
      DC at optimal doses. Finally, the addition of monoclonal antibody (MoAb) anti
      CD86 markedly inhibited SAgs- and ConA-mediated proliferation, whereas MoAb anti
      CD80 had no effect. The combination of both anti-CD80 and anti-CD86, however,
      suppressed this response. These results suggest that bovine gammadelta T-cell
      proliferation response requires indubitably CD86 costimulation. The role of CD80
      molecule seems less clear.

PMID- 11967120
TI  - Primed B cells present type-II collagen to T cells.
AB  - Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on a T
      cell mediated activation of autoreactive B cells. However, it is still unclear if
      B cells can present CII to T cells. To investigate the role of B cells as antigen
      presenting cells (APCs) for CII, we purified B cells from lymph nodes of
      immunized and nonimmunized mice. These B cells were used as APC for antigen
      specific T-cell hybridomas. B cells from naive mice did present native, triple
      helical, CII (nCII) but also ovalbumin (OVA) and denatured CII (dCII) to antigen
      specific T-cell hybridomas. In addition, B cells primed with nCII or OVA, but not
      dCII, activated the antigen-specific T-cell hybridomas two to three times better
      than naive B cells. We conclude that antigen-primed B cells have the capacity to
      process and present CII to primed T cells, and antigen-primed antigen-specific B
      cells are more efficient as APC than naive B cells. We further conclude that B
      cells have the potential to play an important role as APC in the development of
      CIA.

PMID- 11967122
TI  - Chloroquine enhances the number of IL-10 producing cells and the expression of B7
      2 and ICAM-1 in in vitro-cultured PBMC.
AB  - Chloroquine is prescribed as both an anti-malarial and an anti-inflammatory drug.
      However, its immuno-modulating effects remain largely unclear. Previous studies
      have shown that chloroquine inhibits antigen-induced proliferation, implying
      immuno-suppressive effects. In this study, we examined whether the inhibition of
      the proliferation reflects changes in the surface molecules that are important
      for T-cell activation and whether chloroquine affects the balance between pro-
      and anti-inflammatory cytokines. Chloroquine elevated the expression of the
      costimulatory and adhesion molecules B7-2 (CD86) and ICAM-1 (CD54) in peripheral
      mononuclear cells (PBMC). An increased percentage of CD14+ cells was also
      observed, and within this cell population, an increase in ICAM-1 expression was
      revealed by double-staining experiments. Assessment of the frequencies of
      interleukin (IL)-10 and interferon (IFN)-gamma-producing cells in in vitro
      cultivated PBMCs showed that the ratio between pro- and anti-inflammatory
      cytokines changed after exposure to chloroquine, favouring anti-inflammatory
      immune responses. This effect was mainly because of increased frequencies of IL
      10-producing cells and was seen with or without the presence of stimulating
      antigens or mitogens. Our findings indicate that chloroquine affects the
      direction of the lymphocyte stimulation towards an anti-inflammatory response by
      affecting the antigen-presenting cells (APC) and the balance between pro- and
      anti-inflammatory cytokines, rather than generally inhibiting cytokine
      production.

PMID- 11967121
TI  - Chlamydia pneumoniae inhibits apoptosis in human epithelial and monocyte cell
      lines.
AB  - Chlamydia pneumoniae is an obligate intracellular pathogen with a tendency to
      cause persistent infections that has been associated with many chronic conditions
      such as asthma and coronary artery disease. However, its immunopathogenic
      mechanisms are poorly understood. When aiming to study the impact of C.
      pneumoniae infection on host cell apoptosis, we found that epithelial infected
      (HL) cells and macrophages (U937-line) were resistant to staurosporine and tumour
      necrosis factor (TNF)-alpha-induced physiological apoptosis 48, 72 or 120 h post
      infection, as determined by flow cytometry, DNA fragmentation assay and
      fluorescence microscopy. The antiapoptotic influence was observed even at a late
      stage of the chlamydial life cycle and was dependent on the chlamydial protein
      synthesis. The mechanisms involved blockage of mitochondrial cytochrome c release
      and caspase 3 activation. We also found that during a persistent C. pneumoniae
      infection induced in vitro by penicillin treatment of cell cultures, the
      inhibition of apoptosis was extended for up to 120 h of follow-up post-infection
      and was restricted to the cells carrying chlamydial inclusions. Our findings
      suggest that inhibition of apoptosis may be one of the pathogenetic mechanisms by
      which C. pneumoniae infection can mediate the development of chronic diseases.

PMID- 11967123
TI  - Decreased urokinase receptor expression on granulocytes in HIV-infected patients.
AB  - Pericellular proteolysis initiated by receptor-bound urokinase-type plasminogen
      activator (uPA) is considered important for directed migration of granulocytes to
      inflammatory sites. Using flow cytometry and whole-cell binding of radiolabelled
      uPA, we found a high level of uPA-receptor (uPAR) expression in granulocytes (3.9
      x 104 +/- 0.9 x 104 sites/cell). Modulation of uPAR expression was assessed in
      the presence of chemoattractant gradients. Our findings demonstrate that
      interleukin (IL)-8, leukotriene B4(LTB4) and formyl-methionyl-leucyl
      phenylalanine (f MLP) caused a dose-dependent upregulation of uPAR on
      granulocytes in healthy controls. Modulation of uPAR expression is known to
      regulate chemotactic response. As determined by flow cytometry, uPAR expression
      by granulocytes from human immunodeficiency virus (HIV)-infected patients was
      distinctly lower than that of healthy control cells (P < 0.001). However,
      upregulation of uPAR in response to chemoattractants was similar to that observed
      in healthy controls. In HIV-infected patients, the uPAR expression on
      granulocytes correlated (P < 0.001, n = 10) with the number of CD4+ blood cells.
      In contrast, the expression of IL-8 receptor, CD11b, CD18 and CD62 was not
      significantly altered in HIV-patients compared with healthy controls.

PMID- 11967124
TI  - Delayed and reduced adaptive humoral immune responses in children with
      shigellosis compared with in adults.
AB  - We hypothesized that increased susceptibility to Shigella infection, increased
      severity of disease and high mortality in children compared with adults were
      consequences of insufficient adaptive immune responses. Antigen-specific immune
      responses were studied in paediatric patients (n = 38, 2-10 years) with
      shigellosis and compared with those of adult patients (n = 30, 18-45 years). Peak
      frequencies of antigen (invasion plasmid coded antigen B, Ipa-B;
      lipopolysaccharide, LPS)-specific immunoglobulin (IgM)-antibody secreting cells
      (ASC) were seen within 3-5 days after the onset of diarrhoea in children, while
      peak IgA- and IgG-ASCs were obtained 8-10 days later in line with adults. Antigen
      specific ASC responses in children ranged between 2 and 4% of the total ASC
      responses, in contrast to 8-15% in adults. The kinetics of LPS-specific IgG
      subclass titres was different in younger children (2.5-5 years) (IgG1 > IgG2 >
      IgG4 > IgG3) compared with in older children (6-8 years) (IgG2 > IgG1 >IgG3 >
      IgG4) and adults. Secretory IgA levels in stool peaked 8-10 days after onset in
      both adults and children. However, a rapid induction of stool LPS-specific IgA,
      IgA1 and IgA2 occurred in adult patients within 3-5 days of onset, while in
      children, this was delayed by 8-10 days. Similarly, higher number of tumour
      necrosis factor (TNF)-alpha and interferon (IFN)-gamma expressing cells in vitro
      were seen in adult patients in response to antigens (LPS and Ipa-B) in the acute
      stage in contrast to paediatric patients. Thus, paediatric patients with
      shigellosis have reduced and delayed adaptive immune responses compared with
      adult patients.

PMID- 11967125
TI  - Endocytosis via caveolae.
AB  - Caveolae are flask-shaped invaginations present in the plasma membrane of many
      cell types. They have long been implicated in endocytosis, transcytosis, and cell
      signaling. Recent work has confirmed that caveolae are directly involved in the
      internalization of membrane components (glycosphingolipids and
      glycosylphosphatidylinositol-anchored proteins), extracellular ligands (folic
      acid, albumin, autocrine motility factor), bacterial toxins (cholera toxin,
      tetanus toxin), and several nonenveloped viruses (Simian virus 40, Polyoma
      virus). Unlike clathrin-mediated endocytosis, internalization through caveolae is
      a triggered event that involves complex signaling. The mechanism of
      internalization and the subsequent intracellular pathways that the internalized
      substances take are starting to emerge.

PMID- 11967126
TI  - The biogenesis and functions of exosomes.
AB  - Exosomes are membrane vesicles with a diameter of 40-100 nm that are secreted by
      many cell types into the extracellular milieu. They correspond to the internal
      vesicles of an endosomal compartment, the multivesicular body and are released
      upon exocytic fusion of this organelle with the plasma membrane. Intracellularly,
      they are formed by inward budding of the endosomal membrane in a process that
      sequesters particular proteins and lipids. The unique composition of exosomes may
      confer specific functions on them upon secretion. Although their physiological
      role in vivo is far from being unraveled, it is apparent that they function in a
      multitude of processes, including intercellular communication during the immune
      response. Exosomes may have evolved early in the evolution of multicellular
      organisms and also seem to be important for tissue developmental processes.

PMID- 11967128
TI  - RhoGDI-3 regulates RhoG and targets this protein to the Golgi complex through its
      unique N-terminal domain.
AB  - Guanine nucleotide dissociation inhibitors (GDIs) regulate both GDP/GTP and
      membrane association/dissociation cycles of Rho/Rac and Rab proteins.RhoGDI-3 is
      distinguishable from other rhoGDI proteins by its partial association with a
      detergent-resistant subcellular fraction. Here, we investigate the activity of
      this unusual rhoGDI using confocal laser scanning microscopy, immuno-isolation,
      and rhoGDI-3 mutants. We establish that the noncytosolic fraction of rhoGDI-3 is
      associated with the Golgi apparatus. The domain involved in this association is
      the unique N-terminal segment of rhoGDI-3 predicted to form an amphipathic alpha
      helix. This peptide is indispensable for Golgi association of rhoGDI-3 and
      sufficient to address a green fluorescent protein to the Golgi apparatus. Site
      directed mutations, decreasing the hydrophobic surface of the helix, localize
      rhoGDI-3 into the cytoplasm. We establish that rhoGDI-3 is able to inhibit
      activation of the RhoG protein and to target this protein to the Golgi apparatus.
      Furthermore, we demonstrate the importance of the rhoGDI-3 N-terminal segment for
      both Golgi targeting and stability of the cytoplasmic RhoG/rhoGDI-3 complex.
      RhoGDI-3 is the first example of a GDI directly involved in the delivery of a Rho
      protein to a specific subcellular compartment.

PMID- 11967127
TI  - Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated
      endocytosis and the actin cytoskeleton.
AB  - Myosin VI, an actin-based motor protein, and Disabled 2 (Dab2), a molecule
      involved in endocytosis and cell signalling, have been found to bind together
      using yeast and mammalian two-hybrid screens. In polarised epithelial cells,
      myosin VI is known to be associated with apical clathrin-coated vesicles and is
      believed to move them towards the minus end of actin filaments, away from the
      plasma membrane and into the cell. Dab2 belongs to a group of signal transduction
      proteins that bind in vitro to the FXNPXY sequence found in the cytosolic tails
      of members of the low-density lipoprotein receptor family. The central region of
      Dab2, containing two DPF motifs, binds to the clathrin adaptor protein AP-2,
      whereas a C-terminal region contains the binding site for myosin VI. This site is
      conserved in Dab1, the neuronal counterpart of Dab2. The interaction between Dab2
      and myosin VI was confirmed by in vitro binding assays and coimmunoprecipitation
      and by their colocalisation in clathrin-coated pits/vesicles concentrated at the
      apical domain of polarised cells. These results suggest that the myosin VI-Dab2
      interaction may be one link between the actin cytoskeleton and receptors
      undergoing endocytosis.

PMID- 11967130
TI  - Translocation of phosphatidylthreonine and -serine to mitochondria diminishes
      exponentially with increasing molecular hydrophobicity.
AB  - Some cultured cells contain significant amounts of a rarely recognized
      phospholipid, phosphatidylthreonine. Since phosphatidylthreonine is a structural
      analog of phosphatidylserine, the question rises whether it is transported to
      mitochondria and decarboxylated to phosphatidylisopropanolamine therein. We
      studied this issue with hamster kidney cell-line using a novel approach, i.e.
      electrospray mass-spectrometry and stable isotope-labeled precursors. Scanning
      for a neutral loss of 155, which is characteristic for
      phosphatidylisopropanolamine, indicated that this lipid is indeed present. The
      identity of phosphatidylisopropanolamine was supported by the following: (i) it
      co-chromatographed with phosphatidylethanolamine; (ii) its molecular species
      profile was similar to that of phosphatidylethanolamine; (iii) its head group was
      labeled from 13C-threonine; and (iv) its concentration increased in parallel with
      phosphatidylthreonine. Tests with solubilized decarboxylase and subcellular
      fractionation studies indicated that the low cellular content of
      phosphatidylisopropanolamine is due to inefficient decarboxylation, rather than
      poor translocation of phosphatidylthreonine to mitochondria. Importantly, the
      average hydrophobicity of phosphatidylisopropanolamine molecular species was
      significantly less than that of phosphatidylthreonine species, indicating that
      hydrophilic phosphatidylthreonine species translocate to mitochondria far more
      rapidly than hydrophobic ones. Parallel results were obtained for
      phosphatidylserine. These findings imply that efflux from the ER membrane could
      be the rate-limiting step in the phosphatidylthreonine and -serine translocation
      to mitochondria.

PMID- 11967129
TI  - Transfer of GRP94(Gp96)-associated peptides onto endosomal MHC class I molecules.
AB  - GRP94 (gp96)-associated peptides can elicit cellular immune responses, an
      activity thought to reflect the presence of a cell surface receptor (CD91) on
      antigen-presenting cells that mediates GRP94 internalization and trafficking to
      an amenable site for peptide transfer to major histocompatibility complex class I
      molecules. We report that GRP94 internalized by receptor-mediated endocytosis is
      trafficked to a Rab5a, CD1 and transferrin-negative, Fc receptor and major
      histocompatibility complex class I-positive endocytic compartment. Receptor
      internalized GRP94 did not access the endoplasmic reticulum of antigen-presenting
      cells. To identify the site of re-presentation of GRP94-associated peptides,
      kinetic analyses were performed utilizing GRP94-OVA (SIINFEKL) peptide complexes,
      with peptide re-presentation assayed with the Kb-SIINFEKL-specific MAb, 25-D1.16.
      Analyses of the kinetics of re-presentation of GRP94-associated peptides, under
      conditions in which de novo synthesis of major histocompatibility complex class I
      molecules was inhibited, identified a post-endoplasmic reticulum compartment,
      accessed by mature major histocompatibility complex class I, as the predominant
      site of GRP94-associated peptide exchange onto major histocompatibility complex
      class I.

PMID- 11967132
TI  - Audit of red cell transfusion.

PMID- 11967133
TI  - The United Kingdom National External Quality Assessment Scheme (blood transfusion
      laboratory practice): trends in proficiency and practice between 1985 and 2000.
AB  - Proficiency in blood transfusion laboratory practice has improved over the last
      15 years (1985-2000). Error rates for ABO grouping have fallen from 0 x 19 to 0 x
      02% (P = 0 x 003). A similar trend is evident for antibody screening, with error
      rates for false negative antibody screens falling from 3 x 2 to 0 x 5% (P < 0 x
      001), and for antibody identification, for sera containing a single alloantibody,
      with error rates falling from 8 x 8% to 0 x 9% over the last 10 years (P < 0 x
      001). Proficiency in serological crossmatching to detect clinically significant
      non-ABO incompatibilities (other than Kidd), has also improved (P < 0 x 001).
      However, error rates for RhD grouping have not changed and there has been a
      recent decline in proficiency in detecting weak ABO incompatibilities and Kidd
      antibodies with heterozygous cells. Procedures for pretransfusion testing have
      also been rationalized over this time. The indirect antiglobulin test (IAT) is
      used in isolation by 73% of laboratories for antibody screening, and 10% rely on
      the direct room temperature (DRT), immediate spin (IS) crossmatch in the absence
      (current and/or historical) of clinically significant antibodies. Despite the
      improvements in error rates that have occurred alongside the rationalizations,
      there is still evidence of noncompliance with current published BCSH guidelines
      and manufacturers' instructions.

PMID- 11967134
TI  - Monitoring transfusion practice--a computerized procedure.
AB  - As the description of transfusion practice over time requires the handling of
      massive amounts of data, and because the majority of records have until now been
      paper-based, little is known about the epidemiology of blood transfusion.
      Furthermore, most previous studies have collected data manually from patient
      records or from computerized registers created solely for study purposes. We
      describe a procedure for monitoring transfusion practices based exclusively upon
      the collection of data from the existing computerized registers. During the
      calendar years 1997 and 1998, more than 750 000 data records were collected from
      the blood transfusion registers, diagnosis and procedure registers, and clinical
      biochemistry registers at two university hospitals. Linking of the data required
      a unique and consistent identification of all data records. This was made
      possible by the national Personal Identification Number. In this way more than
      98% of all transfusions could be identified and approximately 95% (77 950) could
      be connected to a principal diagnosis. The described procedure creates new
      opportunities for studies of transfusion practices both on a large scale and in
      richness of detail, and we propose to establish a network where transfusion
      practices data are available and comparable for individual departments,
      hospitals, whole regions, and possibly nations.

PMID- 11967135
TI  - Platelet transfusion in the management of severe thrombocytopenia in neonatal
      intensive care unit patients.
AB  - Platelet transfusions are frequently given to neonatal intensive care unit (NICU)
      patients with severe thrombocytopenia (platelets less than 50 x 10(9) L(-1)) but
      no study has assessed whether this is clinically appropriate. To address this we
      conducted a retrospective review of platelet transfusion practice in patients
      developing severe thrombocytopenia over 3 years in a single NICU. Out of 901
      admissions, 53 (6%) developed severe thrombocytopenia. Twenty-seven neonates
      received a total of 63 platelet transfusions, the main triggers being: platelet
      count less than 30 x 10(9) L(-1) (all patients), or less than 50 x 10(9) L(-1) in
      those with previous haemorrhage or clinical instability. No major haemorrhage
      occurred during severe thrombocytopenia either in neonates in whom platelet
      transfusions were withheld (26/53) or in neonates given platelets who survived to
      discharge (22/27). Five preterm neonates given platelets died but all had
      overwhelming sepsis or necrotizing enterocolitis and none died directly as a
      result of haemorrhage. Although the widely used liberal triggers for neonatal
      platelet transfusion highlighted in this review reflect available guidelines, and
      represent cautious ('safe') haemostatic practice, they are likely to result in
      unnecessary transfusion for a significant number of NICU patients. Improved
      practice requires definition of a safe lower limit for platelet count in stable
      neonates; effective platelet transfusion strategies for sick neonates; and
      improved therapies for conditions precipitating severe thrombocytopenia.

PMID- 11967136
TI  - Common human leucocyte antigen haplotypes in Indians--its implications in finding
      unrelated compatible bone marrow donors.
AB  - All over the world there have been efforts to make unrelated stem cell registries
      to cater for patients who do not have a compatible family donor and are in need
      of allogenic stem cell transplantation. Donors of Indian origin are poorly
      represented all these registries. Approximately 10 million Indians live outside
      India, and a substantial number of them live in the developed West. Hence when
      some of these patients of Indian origin need unrelated stem cell donor, they
      search the available National Marrow Donor Program (NMDP) registry database and
      invariably do not get a human leucocyte antigen (HLA) matched donor. They come to
      India, where a haphazard search for the donor ensues and it invariably ends in
      failure. Hence, we have compiled the data of our laboratory and other published
      reports in population HLA studies from India and abroad to show several common
      haplotypes from these studies. It is hoped that this will give the busy clinician
      an idea whether a search for prospective unrelated stem cell donor for an Indian
      patient is likely to succeed or not.

PMID- 11967137
TI  - Analysis of human platelet antigen systems in a Moroccan Berber population.
AB  - The human platelet alloantigen systems HPA-1, -2, -3, -4, -5 and -6 in a Moroccan
      Berber population from the Amizmiz region were determined by polymerase chain
      reaction using sequence-specific primers (PCR-SSP). The gene frequencies obtained
      from these unrelated Berbers were 0 x 747 and 0 x 252 for HPA-1a and -1b; 0 x 817
      and 0 x 182 for HPA-2a and -2b; 0 x 682 and 0 x 317 for HPA-3a and -3b; 1 and 0 x
      0 for HPA-4a and -4b; 0 x 8616 and 0 x 1383 for HPA-5a and -5b; 1 and 0 x 0 for
      HPA-6a and -6b. The Berbers have the highest frequency for the 1b, 2b and 5b
      alleles of all the populations reported to date and also the lowest frequency for
      the 3b allele.

PMID- 11967138
TI  - JAHK: a low frequency antigen associated with the rG complex of the Rh blood
      group system.
AB  - We have investigated a 'new' low frequency antigen JAHK, which is a marker for
      the rare Rh gene complex rG. The rG haplotype does not produce any D, c or E
      antigens, but does produce a strong G antigen. The rG haplotype [d(C)(e)G] is
      associated with weak C and weak e antigens. Three unrelated rG/dce individuals
      and one rG/rG propositus were JAHK+. In addition, three propositi whose red cells
      had a typical expression of C and/or e antigen, which could not be shown to be rG
      because of a normal D antigen produced by the haplotype in trans, were also
      JAHK+. Families of three of the propositi demonstrate the inheritance of JAHK as
      a Mendelian dominant character. It is likely that the JAHK antigen results from
      conformational changes in an RhCcEe protein that has the amino acid
      characteristic of c antigen at position 16 and the amino acid residues
      characteristic of C antigen at positions 60, 68, and 103. JAHK has been assigned
      the number RH53.

PMID- 11967139
TI  - Comparison of low ionic diluents for use with the Diamed antiglobulin gel test.
AB  - Microtube column systems, although widely used in transfusion serology for the
      detection of red cell antibodies, may not detect weak Fy(a), Jk(a), S and K
      antibodies. A number of low ionic diluents are used to shorten the incubation
      time required for red cell antibody detection in the antiglobulin test. However,
      there are no published reports to show whether these low ionic diluents vary in
      their ability to detect red cell antibodies using microcolumn detection systems.
      Three low ionic diluents, Diamed ID-CellStab, Diamed ID-Diluent2 and an in-house
      produced low ionic strength solution (LISS), were assessed using the Diamed-ID
      LISS/Coombs microtube column system (in accordance with the manufacturer's
      instructions), to ascertain whether the choice of diluent influences red cell
      antibody detection. Two hundred and seventy patient samples were screened for red
      cell antibodies. The reaction strength was increased in 50% of the samples with
      detectable red cell antibodies using LISS as the diluent compared with ID
      CellStab. Of the 51 red cell antibodies directed against Rhesus, Duffy, Kidd or
      Kell antigens, 21% reacted more strongly in LISS compared with Diamed ID-CellStab
      with a difference in grading of > or =1. Minimal disparity was found between ID
      Diluent2 and LISS. Biochemical analysis of pH, osmolality, sodium, potassium and
      phosphate were comparable for ID-CellStab, ID-Diluent2 and LISS. Measurement of
      conductivity in each low ionic diluent was performed as a measure of ionic
      strength in the final reactant mix, as the same amount of low ionic diluent was
      used for each test. The conductivity was 3 x 5 mS cm for LISS and ID-Diluent2,
      and 5 x 8 mS cm for ID-CellStab; the acceptable range being 3 x 7 +/- 0 x 3 mS cm
      as cited in the Guidelines for the Blood Transfusion Services in the United
      Kingdom. This evaluation suggests that ID-CellStab is a suboptimal low ionic
      diluent for red cell antibody detection using Diamed-ID LISS/Coombs gel cards.
      The poorer performance of ID-CellStab compared with LISS may be explained by its
      higher ionic strength.

PMID- 11967140
TI  - Effectiveness of washed platelet concentrate and red cell transfusions for a
      patient with anhaptoglobinemia with antihaptoglobin antibody.
AB  - A 71-year-old Japanese male with myelodysplastic syndrome progressing to overt
      leukaemia and hepatocellular carcinoma developed dyspnea and urticaria
      immediately after infusion of platelet concentrate (PC). He exhibited an
      identical reaction following blood transfusion. Serum haptoglobin was
      undetectable. The patient was determined to be homozygous for Hp(del) by
      polymerase chain reaction (PCR). Antibody to haptoglobin was detected by enzyme
      linked immunosorbent assay (ELISA) and Western blot analysis. No antibodies
      against human leucocyte antigen (HLA) or platelet-specific antigens were
      detected. Washed PC and washed red blood cells were effective in preventing the
      transfusion-related anaphylactoid reactions.

PMID- 11967141
TI  - Successful long-term erythrocytapheresis therapy in a patient with symptomatic
      sickle-cell disease using an arterio-venous fistula.
AB  - The use of long-term automated erythrocytapheresis via an arterio-venous fistula
      for the prevention of recurrent ischaemic stroke in a child with sickle-cell
      disease (SCD) has not been described previously. We report the successful use of
      this technique in a 13-year-old boy. A procedure was performed every 36 +/- 6
      days, transfusing six units of donor packed red blood cells (RBCs) and discarding
      1318 +/- 174 mL of exchanged erythrocytes (Hct 60%). After transfusion of 85
      units over 17 months, there is no evidence for iron-overload, red cell
      alloimmunization, transfusion-transmitted infections, or other complications.
      Until now, no cerebrovascular ischaemia has been observed.

PMID- 11967142
TI  - Leukodepleted blood products: who really needs them?

PMID- 11967143
TI  - Failed screen test audit.

PMID- 11967145
TI  - A bovine papillomavirus-1 based vector restores the function of the low-density
      lipoprotein receptor in the receptor-deficient CHO-ldlA7 cell line.
AB  - BACKGROUND: The rationale of using bovine papillomavirus-1 (BPV-1) derived
      vectors in gene therapy protocols lies in their episomal maintenance at
      intermediate to high copy number, and stable, high-level expression of the gene
      products. We constructed the BPV-1 based vector harbouring the human low-density
      lipoprotein receptor (LDLR) gene cDNA and tested its ability to restore the
      function of the LDLR in the receptor-deficient cell line CHO-ldlA7. RESULTS: The
      introduced vector p3.7LDL produced functionally active LDL receptors in the
      receptor-deficient cell line CHO-ldlA7 during the 32-week period of observation
      as determined by the internalisation assay with the labelled LDL particles.
      CONCLUSION: Bovine papillomavirus type-1 (BPV-1)-derived vectors could be
      suitable for gene therapy due to their episomal maintenance at intermediate to
      high copy number and stable, high-level expression of the gene products. The
      constructed BPV-1 based vector p3.7LDL produced functionally active LDL receptors
      in the LDLR-deficient cell line CHO-ldlA7 during the 32-week period of
      observation. In vivo experiments should reveal, whether 1-5% transfection
      efficiency obtained in the current work is sufficient to bring about detectable
      and clinically significant lowering of the amount of circulating LDL cholesterol
      particles.

PMID- 11967146
TI  - The impact of incident vertebral and non-vertebral fractures on health related
      quality of life in postmenopausal women.
AB  - BACKGROUND: Little empirical research has examined the multiple consequences of
      osteoporosis on quality of life. METHODS: Health related quality of life (HRQL)
      was examined in relationship to incident fractures in 2009 postmenopausal women
      50 years and older who were seen in consultation at our tertiary care, university
      teaching hospital-affiliated office and who were registered in the Canadian
      Database of Osteoporosis and Osteopenia (CANDOO) patients. Patients were divided
      into three study groups according to incident fracture status: vertebral
      fractures, non-vertebral fractures and no fractures. Baseline assessments of
      anthropometric data, medical history, therapeutic drug use, and prevalent
      fracture status were obtained from all participants. The disease-targeted mini
      Osteoporosis Quality of Life Questionnaire (mini-OQLQ) was used to measure HRQL.
      RESULTS: Multiple regression analyses revealed that subjects who had experienced
      an incident vertebral fracture had lower HRQL difference scores as compared with
      non-fractured participants in total score (-0.86; 95% confidence intervals (CI): 
      1.30, -0.43) and the symptoms (-0.76; 95% CI: -1.23, -0.30), physical functioning
      (-1.12; 95% CI: -1.57, -0.67), emotional functioning (-1.06; 95% CI: -1.44, 
      0.68), activities of daily living (-1.47; 95% CI: -1.97, -0.96), and leisure (
      0.92; 95% CI: -1.37, -0.47) domains of the mini-OQLQ. Patients who experienced an
      incident non-vertebral fracture had lower HRQL difference scores as compared with
      non-fractured participants in total score (-0.47; 95% CI: -0.70, -0.25), and the
      symptoms (-0.25; 95% CI: -0.49, -0.01), physical functioning (-0.39; 95% CI: 
      0.65, -0.14), emotional functioning (-0.97; 95% CI: -1.20, -0.75) and the
      activities of daily living (-0.47; 95% CI: -0.73, -0.21) domains. CONCLUSION:
      Quality of life decreased in patients who sustained incident vertebral and non
      vertebral fractures.

PMID- 11967147
TI  - Two kinesin-like Kin I family proteins in fission yeast regulate the
      establishment of metaphase and the onset of anaphase A.
AB  - BACKGROUND: Metaphase is thought to be a force-equilibrium state of "tug of war,"
      in which poleward forces are pulling kinetochores and counteracting the cohesive
      forces between the centromeres. Unlike conventional kinesins, members of the Kin
      I family are microtubule-depolymerizing enzymes, which are expected to be
      molecules that could generate poleward forces. RESULTS: We have characterized
      mitotic roles of two Kin I homologs, Klp5 and Klp6, in fission yeast. Klp5 and
      Klp6 colocalize to the mitotic kinetochores and the spindle midzone. These two
      proteins form a heterocomplex, but not a homocomplex. Albeit not essential, both
      proteins are required for accurate chromosome segregation and normal morphology
      of interphase microtubules. Time-lapse live analysis using GFP-alpha-tubulin
      indicates that these mutants spend a much longer time (2-fold) in mitosis before
      the initiation of anaphase B. Further observation using kinetochore and
      centromere markers shows that, in these mutants, sister centromeres move back and
      forth between the two poles, indicating that entry into anaphase A is delayed.
      This is supported by live image analysis showing that Cut2 securin is retained
      during the prolonged mitosis. Furthermore, the mitotic extension is dependent
      upon the Mad2 spindle checkpoint. CONCLUSIONS: We discuss two models of Kin I
      function in fission yeast. One proposes that Klp5 and Klp6 are required for
      efficient capturing of kinetochores by the spindles, while the other proposes
      that they are required to generate tension upon kinetochore capturing. Kin I,
      therefore, plays a fundamental role in the establishment of metaphase, probably
      by generating poleward forces at the kinetochores.

PMID- 11967148
TI  - A conserved interaction between beta1 integrin/PAT-3 and Nck-interacting
      kinase/MIG-15 that mediates commissural axon navigation in C. elegans.
AB  - BACKGROUND: Integrins are heterodimeric (alphabeta) transmembrane receptors for
      extracellular matrix (ECM) ligands. Through interactions with molecular partners
      at cell junctions, they provide a connection between the ECM and the cytoskeleton
      and regulate many aspects of cell behavior. A number of integrin-associated
      molecules have been identified; however, in many cases, their function and role
      in the animal remain to be clarified. RESULTS: We have identified the Nck
      interacting kinase (NIK), a member of the STE20/germinal center kinase (GCK)
      family, as a partner for the beta1A integrin cytoplasmic domain. We find that NIK
      is expressed in the nervous system and other tissues in mouse embryos and
      colocalizes with actin and beta1 integrin in cellular protrusions in transfected
      cells. To demonstrate the functional significance of this interaction, we used
      Caenorhabditis elegans, since it has only one beta (PAT-3) integrin chain, two
      alpha (INA-1 and PAT-2) integrin chains, and a well-conserved NIK ortholog (MIG
      15). Using three methods, we show that reducing mig-15 activity results in
      premature branching of commissures. A significant aggravation of this defect is
      observed when mig-15 activity is compromised in a weak ina-1 background. Neuronal
      specific RNA interference against mig-15 or pat-3 leads to similar axonal
      defects, thus showing that both mig-15 and pat-3 act cell autonomously in
      neurons. Finally, we show a genetic interaction between mig-15, ina-1, and genes
      that encode Rac GTPases. CONCLUSIONS: Using several models, we provide the first
      evidence that the kinase NIK and integrins interact in vitro and in vivo. This
      interaction is required for proper axonal navigation in C. elegans.

PMID- 11967149
TI  - Identification of a conserved motif required for mTOR signaling.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) controls the translation
      machinery via activation of S6 kinases 1 and 2 (S6K1/2) and inhibition of the
      eukaryotic initiation factor 4E (eIF4E) binding proteins 1, 2, and 3 (4E
      BP1/2/3). S6K1 and 4E-BP1 are regulated by nutrient-sensing and mitogen-activated
      pathways. The molecular basis of mTOR regulation of S6K1 and 4E-BP1 remains
      controversial. RESULTS: We have identified a conserved TOR signaling (TOS) motif
      in the N terminus of all known S6 kinases and in the C terminus of the 4E-BPs
      that is crucial for phosphorylation and regulation S6K1 and 4E-BP1 activities.
      Deletion or mutations within the TOS motif significantly inhibit S6K1 activation
      and the phosphorylation of its hydrophobic motif, Thr389. In addition, this
      sequence is required to suppress an inhibitory activity mediated by the S6K1 C
      terminus. The TOS motif is essential for S6K1 activation by mTOR, as mutations in
      this motif mimic the effect of rapamycin on S6K1 phosphorylation, and render S6K1
      insensitive to changes in amino acids. Furthermore, only overexpression of S6K1
      with an intact TOS motif prevents 4E-BP1 phosphorylation by a common mTOR
      regulated modulator of S6K1 and 4E-BP1. CONCLUSIONS: S6K1 and 4E-BP1 contain a
      conserved five amino acid sequence (TOS motif) that is crucial for their
      regulation by the mTOR pathway. mTOR seems to regulate S6K1 by two distinct
      mechanisms. The TOS motif appears to function as a docking site for either mTOR
      itself or a common upstream activator of S6K1 and 4E-BP1.

PMID- 11967150
TI  - Drosophila Aurora-A is required for centrosome maturation and actin-dependent
      asymmetric protein localization during mitosis.
AB  - BACKGROUND: During asymmetric cell division in the Drosophila nervous system,
      Numb segregates into one of two daughter cells where it is required for the
      establishment of the correct cell fate. Numb is uniformly cortical in interphase,
      but in late prophase, the protein concentrates in the cortical area overlying one
      of two centrosomes in an actin/myosin-dependent manner. What triggers the
      asymmetric localization of Numb at the onset of mitosis is unclear. RESULTS: We
      show here that the mitotic kinase Aurora-A is required for the asymmetric
      localization of Numb. In Drosophila sensory organ precursor (SOP) cells mutant
      for the aurora-A allele aurA(37), Numb is uniformly localized around the cell
      cortex during mitosis and segregates into both daughter cells, leading to cell
      fate transformations in the SOP lineage. aurA(37) mutant cells also fail to
      recruit Centrosomin (Cnn) and gamma-Tubulin to centrosomes during mitosis,
      leading to spindle morphology defects. However, Numb still localizes
      asymmetrically in cnn mutants or after disruption of microtubules, indicating
      that there are two independent functions for Aurora-A in centrosome maturation
      and asymmetric protein localization during mitosis. Using photobleaching of a GFP
      Aurora fusion protein, we show that two rapidly exchanging pools of Aurora-A are
      present in the cytoplasm and at the centrosome and might carry out these two
      functions. CONCLUSIONS: Our results suggest that activation of the Aurora-A
      kinase at the onset of mitosis is required for the actin-dependent asymmetric
      localization of Numb. Aurora-A is also involved in centrosome maturation and
      spindle assembly, indicating that it regulates both actin- and microtubule
      dependent processes in mitotic cells.

PMID- 11967151
TI  - A murine model of Nijmegen breakage syndrome.
AB  - Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder
      characterized by microcephaly, immunodeficiency, and predisposition to
      hematopoietic malignancy. The clinical and cellular phenotypes of NBS
      substantially overlap those of ataxia-telangiectasia (A-T). NBS is caused by
      mutation of the NBS1 gene, which encodes a member of the Mre11 complex, a
      trimeric protein complex also containing Mre11 and Rad50. Several lines of
      evidence indicate that the ataxia-telangiectasia mutated (ATM) kinase and the
      Mre11 complex functionally interact. Both NBS and A-T cells exhibit ionizing
      radiation (IR) sensitivity and defects in the intra S phase checkpoint, resulting
      in radioresistant DNA synthesis (RDS)-the failure to suppress DNA replication
      origin firing after IR exposure. NBS1 is phosphorylated by ATM in response to IR,
      and this event is required for activation of the intra S phase checkpoint (the
      RDS checkpoint). We derived a murine model of NBS, the Nbs1(DeltaB/DeltaB) mouse.
      Nbs1(DeltaB/DeltaB) cells are phenotypically identical to those established from
      NBS patients. The Nbs1(DeltaB) allele was synthetically lethal with ATM
      deficiency. We propose that the ATM-Mre11 complex DNA damage response pathway is
      essential and that ATM or the Mre11 complex serves as a nexus to additional
      components of the pathway.

PMID- 11967152
TI  - A pharmacogenetic inducible approach to the study of NMDA/alphaCaMKII signaling
      in synaptic plasticity.
AB  - We recently introduced an inducible pharmacogenetic approach where
      pharmacological manipulations can be used to reveal recessive mutant phenotypes
      in a temporally controlled manner. This approach takes advantage of synergisms
      between pharmacological and genetic manipulations to alter the function of
      specific signaling pathways. For example, mice heterozygous for a point mutation
      (T286A) in the alpha-calcium/calmodulin-dependent kinase II (alphaCaMKII) gene
      show normal learning and memory. However, a concentration of an NMDA receptor
      antagonist (CPP) that does not affect learning in wild-type (WT) littermates,
      reveals learning deficits in this heterozygote (alphaCaMKII(T286A+/-)). Here, we
      show that pretetanic application of a concentration of CPP (0.1 microM)
      ineffective in WT hippocampal slices induced deficits in alphaCaMKII(T286A+/-)
      slices in hippocampal long-term potentiation (LTP), a mechanism thought to be
      involved in learning and memory. Importantly, posttetanic application of CPP (0.1
      microM) had no effect on the expression or maintenance of LTP in hippocampal
      slices from alphaCaMKII(T286A+/-) mice. Thus, this pharmacogenetic approach
      allowed us to demonstrate that NMDA receptor-dependent autophosphorylation of
      alphaCaMKII is required during the induction but not maintenance of LTP. This
      ability to temporally induce recessive mutant phenotypes could be applicable to a
      broad range of problems and genetic systems.

PMID- 11967153
TI  - Trichromacy in Australian marsupials.
AB  - Vertebrate color vision is best developed in fish, reptiles, and birds with four
      distinct cone receptor visual pigments. These pigments, providing sensitivity
      from ultraviolet to infrared light, are thought to have been present in ancestral
      vertebrates. When placental mammals adopted nocturnality, they lost two visual
      pigments, reducing them to dichromacy; primates subsequently reevolved
      trichromacy. Studies of mammalian color vision have largely overlooked marsupials
      despite the wide variety of species and ecological niches and, most importantly,
      their retention of reptilian retinal features such as oil droplets and double
      cones. Using microspectrophotometry (MSP), we have investigated the spectral
      sensitivity of the photoreceptors of two Australian marsupials, the crepuscular,
      nectivorous honey possum (Tarsipes rostratus) and the arhythmic, insectivorous
      fat-tailed dunnart (Sminthopsis crassicaudata); these species are representatives
      of the two major taxonomic divisions of marsupials, the diprotodonts and
      polyprotodonts, respectively. Here, we report the presence of three spectrally
      distinct cone photoreceptor types in both species. It is the first evidence for
      the basis of trichromatic color vision in mammals other than primates. We suggest
      that Australian marsupials have retained an ancestral visual pigment that has
      been lost from placental mammals.

PMID- 11967154
TI  - Cyclin D-cdk4 is not a master regulator of cell multiplication in Drosophila
      embryos.
AB  - Inactivation of Cyclin E-Cdk2 is essential for a timely arrest of the epidermal
      cell proliferation program during Drosophila embryogenesis. E-type cyclin-cdk
      complexes are thought to be activated by D-types titrating away inhibitors and
      inducing cyclin E transcription by activating E2F transcription factors via Rb
      phosphorylation. Therefore, we have analyzed whether the developmentally
      controlled inactivation of Cyclin E-Cdk2 required for the epidermal cell
      proliferation arrest occurs as a consequence of Cyclin D-Cdk4 inactivation.
      However, preventing Cyclin D-Cdk4 inactivation by overexpression has a minimal
      effect on Cyclin E expression and does not interfere with the initial G1 arrest,
      while it readily induces the E2F target RnrS in arresting epidermal cells.
      Prolonged Cyclin D-Cdk4 overexpression eventually interferes with maintenance of
      quiescence in some cells. Moreover, in Cdk4 mutant embryos, some RnrS expression
      is still induced by Cyclin E overexpression, and endogenous Cyclin E expression
      as well as cell cycle progression is not affected, except for late aspects of the
      endoreduplication program. These findings argue against the proposed necessity of
      complete Rb inactivation by sequential phosphorylation by D- and E-type cyclin
      cdk complexes. They demonstrate that Cyclin D-Cdk4 does not function as the
      master regulator of the embryonic cell proliferation program.

PMID- 11967155
TI  - The COP9 signalosome inhibits p27(kip1) degradation and impedes G1-S phase
      progression via deneddylation of SCF Cul1.
AB  - The COP9 signalosome (CSN) is a conserved protein complex with homologies to the
      lid subcomplex of the 26S proteasome. It promotes cleavage of the Nedd8 conjugate
      (deneddylation) from the cullin component of SCF ubiquitin ligases. We provide
      evidence that cullin neddylation and deneddylation is highly dynamic, that its
      equilibrium can be effectively modulated by CSN, and that neddylation allows Cul1
      to form larger protein complexes. CSN2 integrates into the CSN complex via its C
      terminal region and its N-terminal half region is necessary for direct
      interaction with Cul1. The polyclonal antibodies against CSN2 but not other CSN
      subunits cause accumulation of neddylated Cul1/Cul2 in HeLa cell extract,
      indicating that CSN2 is essential in cullin deneddylation. Further, CSN inhibits
      ubiquitination and degradation of the cyclin-dependent kinase inhibitor p27(kip1)
      in vitro. Microinjection of the CSN complex impeded the G1 cells from entering
      the S phase. Moreover, anti-CSN2 antibodies negate the CSN-dependent p27
      stabilization and the G1/S blockage, suggesting that these functions require the
      deneddylation activity. We conclude that CSN inhibits SCF ubiquitin ligase
      activity in targeting p27 proteolysis and negatively regulates cell cycle at the
      G1 phase by promoting deneddylation of Cul1.

PMID- 11967156
TI  - Gene flow from the Indian subcontinent to Australia: evidence from the Y
      chromosome.
AB  - Phenotypic similarities between Australian Aboriginal People and some tribes of
      India were noted by T.H. Huxley during the voyage of the Rattlesnake (1846-1850).
      Anthropometric studies by Birdsell led to his suggestion that a migratory wave
      into Australia included populations with affinities to tribal Indians. Genetic
      evidence for an Indian contribution to the Australian gene pool is contradictory;
      most studies of autosomal markers have not supported this hypothesis (; and
      references therein). On the other hand, affinities between Australian Aboriginal
      People and southern Indians were suggested based on maternally inherited
      mitochondrial DNA. Here, we show additional DNA evidence in support of Huxley's
      hypothesis of an Indian-Australian connection using single-nucleotide
      polymorphisms (SNPs) and short tandem repeats (STRs) on the nonrecombining
      portion of the Y chromosome (NRY). Phylogenetic analyses of STR variation
      associated with a major Australian SNP lineage indicated tight clustering with
      southern Indian/Sri Lankan Y chromosomes. Estimates of the divergence time for
      these Indian and Australian chromosomes overlap with important changes in the
      archaeological and linguistic records in Australia. These results provide strong
      evidence for an influx of Y chromosomes from the Indian subcontinent to Australia
      that may have occurred during the Holocene.

PMID- 11967157
TI  - Geminin becomes activated as an inhibitor of Cdt1/RLF-B following nuclear import.
AB  - During late mitosis and early interphase, origins of replication become
      "licensed" for DNA replication by loading Mcm2-7 complexes. Mcm2-7 complexes are
      removed from origins as replication forks initiate replication, thus preventing
      rereplication of DNA in a single cell cycle. Premature origin licensing is
      prevented in metaphase by the action of geminin, which binds and inhibits
      Cdt1/RLF-B, a protein that is required for the loading of Mcm2-7. Recombinant
      geminin that is added to Xenopus egg extracts is efficiently degraded upon exit
      from metaphase. Here, we show that recombinant and endogenous forms of Xenopus
      geminin behave differently from one another, such that a significant proportion
      of endogenous geminin escapes proteolysis upon exit from metaphase. During late
      mitosis and early G1, the surviving population of endogenous geminin does not
      associate with Cdt1/RLF-B and does not inhibit licensing. Following nuclear
      assembly, geminin is imported into nuclei and becomes reactivated to bind
      Cdt1/RLF-B. This reactivated geminin provides the major nucleoplasmic inhibitor
      of origin relicensing during late interphase. Since the initiation of replication
      at licensed origins depends on nuclear assembly, our results suggest an elegant
      and novel mechanism for preventing rereplication of DNA in a single cell cycle.

PMID- 11967160
TI  - US-style creationism spreads to Europe.

PMID- 11967161
TI  - A hidden coral destruction.

PMID- 11967159
TI  - Identification of Tah11/Sid2 as the ortholog of the replication licensing factor
      Cdt1 in Saccharomyces cerevisiae.
AB  - Faithful duplication of the genetic material requires that replication origins
      fire only once per cell cycle. Central to this control is the tightly regulated
      formation of prereplicative complexes (preRCs) at future origins of DNA
      replication. In all eukaryotes studied, this entails loading by Cdc6 of the Mcm2
      7 helicase next to the origin recognition complex (ORC). More recently, another
      factor, named Cdt1, was shown to be essential for Mcm loading in fission yeast
      and Xenopus as well as for DNA replication in Drosophila and humans.
      Surprisingly, no Cdt1 homolog was found in budding yeast, despite the conserved
      nature of origin licensing. Here we identify Tah11/Sid2, previously isolated
      through interactions with topoisomerase and Cdk inhibitor mutants, as an ortholog
      of Cdt1. We show that sid2 mutants lose minichromosomes in an ARS number
      dependent manner, consistent with ScCdt1/Sid2 being involved in origin licensing.
      Accordingly, cells partially depleted of Cdt1 replicate DNA from fewer origins,
      whereas fully depleted cells fail to load Mcm2 on chromatin and fail to initiate
      but not elongate DNA synthesis. We conclude that origin licensing depends in S.
      cerevisiae as in other eukaryotes on both Cdc6 and Cdt1.

PMID- 11967158
TI  - A branched pathway for transgene-induced RNA silencing in plants.
AB  - In plants, RNA silencing can be induced by highly transcribed sense transgenes (S
      PTGS) or by transgene loci producing double-stranded RNA (dsRNA) due to the
      presence of inverted repeats (IR-PTGS). Both phenomena correlate with
      accumulation of 21-25 nt sense and anti-sense RNA homologous to the silent gene
      and with methylation of the coding sequence. We have challenged IR-PTGS with four
      viruses known to inhibit S-PTGS: CMV, TuMV, TVCV, and TCV ( this work) and in
      sgs2, sgs3, and ago1 mutants impaired in S-PTGS. Surprisingly, whereas the four
      viruses inhibit IR-PTGS, IR-PTGS and methylation of a GUS trangene and IR-PTGS of
      three endogeneous genes occur in the sgs2, sgs3, and ago1 mutations. Based on
      these results, we propose a branched pathway for RNA silencing in plants. RNA
      silencing would occur via the action of dsRNA produced either via the action of
      SGS2 (also known as SDE1), SGS3, and AGO1 on the S-PTGS branch or by transgenes
      arranged as inverted repeats on the IR-PTGS branch. Moreover, transgene
      methylation would result from production or action of dsRNA, since it does not
      require SGS2/SDE1, SGS3, and AGO1.

PMID- 11967162
TI  - Feature: Europe ramps up its research goals.

PMID- 11967164
TI  - Primer: altruism.

PMID- 11967165
TI  - BMP signalling: visualisation of the Sog protein gradient.
AB  - Extracellular inhibitors are commonly used in development to modulate the
      activities of signalling molecules. Direct visualisation in the Drosophila embryo
      of Sog, a Dpp/Scw inhibitor, has now revealed a graded distribution established
      by degradation and endocytosis.

PMID- 11967163
TI  - Quick guide: target of rapamycin.

PMID- 11967166
TI  - Selfish DNA: new abode for homing endonucleases.
AB  - A 30-year old conundrum concerning the genetics of T-even bacteriophages has at
      last been solved, the answer turning out to involve free-standing homologs of
      intron-encoded homing endonucleases.

PMID- 11967167
TI  - Elastic fibers: building bridges between cells and their matrix.
AB  - Extracellular elastic fibers confer resilience and flexibility to tissues. Recent
      studies have identified a protein, fibulin-5, that connects these fibers to cells
      and regulates their assembly and organization.

PMID- 11967168
TI  - Visual neurons: categorization-based selectivity.
AB  - A computational framework that can account for object categorization and
      identification has gained empirical support from recent studies of monkey
      behavior and neurophysiology.

PMID- 11967169
TI  - Messenger RNA degradation: beginning at the end.
AB  - The mechanisms responsible for mRNA decay in mammalian cells, and how specific
      sequence elements accelerate decay, are unknown. Recent work indicates that 'ARE'
      instability elements recruit the exosome to promote rapid 3'-to-5' degradation of
      the mRNA.

PMID- 11967170
TI  - Kinase regulation: competing phosphatases in JAK dephosphorylation.
AB  - The Janus kinases (JAKs) are essential for cytokine receptor signalling and their
      dephosphorylation represents a potent inhibitory mechanism. A new paper
      highlights the T-cell tyrosine phosphatase as an important JAK inhibitor.

PMID- 11967172
TI  - Genome sequencing: and then there were six.
AB  - The genome of the fission yeast Schizosaccharomyces pombe has been sequenced,
      bringing the number of sequenced eukaryotic genomes to six. Analysis of the
      sequence predicts only 4824 protein coding genes, the smallest number yet
      recorded for a free-living eukaryote.

PMID- 11967171
TI  - Developmental evolution: Hox proteins ring the changes.
AB  - The evolution of body form is believed to involve changes in expression of
      developmental genes, largely through changes in cis-regulatory elements. Recent
      studies suggest that changes in the sequences of key developmental regulators,
      such as the Hox proteins, may also play an important role.

PMID- 11967173
TI  - Bacterial surface motility: slime trails, grappling hooks and nozzles.

PMID- 11967174
TI  - Epilepsy and epileptic disorders, an epidemiological marker? Contribution of
      descriptive epidemiology.
AB  - Numerous epidemiological studies concerning the incidence and prevalence of
      epilepsy and epileptic seizures have been performed in different geographical
      areas throughout the world. The results of these studies show some disparities in
      the evaluation of incidence and prevalence rates. Higher incidence rates have
      been reported in a few studies performed in developing countries. Many prevalence
      studies seem to corroborate this figure although more recent surveys report
      similar rates to those observed in the developed world. These controversial
      results are discussed because there is no scientific reason that the clinical
      aspects and natural evolution of the disease should be different between
      developed and developing countries. However, some epidemic or endemic diseases
      might explain, in part, these figures. On the other hand, the age and sex
      distribution of the disease seems to be specific to epilepsy and could be related
      to particular risk factors and some demographic considerations. Apart from
      obvious methodological biases, the results of these studies lead us to recognize
      that epilepsy is universal   it can occur in any people   and is ubiquitous  
      i.e. it is observed in every country   but is not an equally distributed disease.
      Epileptic seizures and epilepsy might be considered as an epidemiological marker
      of some endemo-epidemic diseases or the results of certain preventive measures.

PMID- 11967175
TI  - Sleep-related, low voltage Rolandic and vertex spikes: an EEG marker of benignity
      in infancy-onset focal epilepsies.
AB  - Although benign forms of epilepsies with onset in infancy have recently been
      recognized, the occurrence of seizures in an infant or very young child is very
      often an event of great significance and the prognosis concerning both epilepsy
      and neuropsychological development must be guarded. No reliable clinical or
      electroencephalographic (EEG) markers that can predict the outcome have been
      described. In a retrospective series of 10 patients, we found a peculiar EEG
      pattern seen across sleep stages, but not in the waking state in infants whose
      first seizures appeared before the age of 1 year, and which were mostly complex
      focal. In all cases, follow-up showed a favourable outcome with complete seizure
      remission and no cognitive impairment. The specificity of these EEG changes was
      100%, but the sensitivity was lower, since they were not seen in some of the
      infants with the same favourable outcome. We discuss the clinical similarities
      between our patients and those cases reported earlier by other authors as benign,
      non-familial or familial focal epilepsies, in whom, however, no interictal
      abnormalities had been seen on the EEG. Such EEG changes are probably specific to
      benign, self-limited, early onset focal epilepsies.

PMID- 11967176
TI  - Epileptic nystagmus: a case study video-EEG correlation.
AB  - Epileptic nystagmus (EN) is an uncommon phenomenon characterized by repetitive
      and rapid saccades, in association with epileptic discharges. We present a
      critical video-EEG recording in a patient with occipital seizures that appeared
      clinically as EN. The subject, male, 70 years-old, was examined because of
      generalized tonic-clonic seizures, preceded by left cephalic version. These were
      controlled using i.v. PHT, but partial seizures persisted, which we recorded
      using video-EEG. Clinically, we observed episodes of left conjugate deviation of
      the eyes, accompanied by horizontal nystagmoid movements, with a rapid leftward
      component and visual hallucinations. The patient did not lose consciousness.
      Ictal EEG: spike rhythm in the posterior right occipito-temporal region extending
      to adjacent and contralateral regions, followed by post-discharge of slow waves.
      The video-EEG was interpreted as partial oculo-clonic status epilepticus of right
      temporo-occipital origin. Cranial MRI: old, bilateral hemorrhaging occipital
      contusions associated with previous cranial injury. The picture persisted for two
      days, and disappeared with administration of CBZ 600 mg/d. Our patient's
      nystagmus seemed to be related to the critical activity recorded in the right
      occipito-temporal region. The co-existence of visual hallucinations and the video
      EEG correlation support this possibility. This phenomenon is probably due to
      epileptic activation of the cortical center of saccadic movements, with a rapid
      phase of nystagmus, contralateral to the focus, and a slow ipsilateral phase in
      association with a defect in the gaze-fixing system ("leaky neural integrator")
      [published with videosequences].

PMID- 11967177
TI  - Benign early infantile reflex absence seizures.
AB  - This case report, with videotape, focuses on reflex epileptic seizures of a girl
      who started to have seizures, provoked by tactile stimuli, at the age of twelve
      months. They were described as myoclonic jerks predominantly in the upper part of
      the body and the arms. During video/EEG monitoring at the age of fifteen months,
      seizures provoked by the same tactile stimuli were recorded. For clinical and
      electroencephalographic reasons, these are best described as absence seizures
      (persistence of minimal myoclonic jerking). To our knowledge, such seizures at
      this age have not been documented before. Treatment with antiepileptic agents was
      not initiated. Six months later the seizures stopped spontaneously and have not
      recurred. Two years later, psychomotor and behavioural development is normal
      [published with video- sequences].

PMID- 11967178
TI  - Atypical evolution of Panayiotopoulos syndrome: a case report.
AB  - Panayiotopoulos syndrome is a relatively common condition with susceptibility to
      early onset benign childhood seizures, which manifests primarily with autonomic
      and mainly emetic symptoms. It predominantly affects children of 3-6 years of age
      (13% of those with one or more non-febrile seizures). EEG shows great
      variability, with occipital, extra-occipital spikes or brief generalised
      discharges alone or in combination; it may also be consistently normal. Occipital
      spikes do not occur in one third of children. Despite the high prevalence of
      autonomic status epilepticus, the prognosis of Panayiotopoulos syndrome is
      usually excellent. Remission usually occurs within 1-2 years from onset, one
      third have a single seizure but 5-10% may have more than 10 seizures or a more
      prolonged course. Atypical evolutions with absences, atonic seizures and
      intellectual deterioration are exceptional; only two cases have been previously
      reported. We present a girl who initially had a prolonged autonomic status
      epilepticus typical of Panayiotopoulos syndrome, followed by seizures, with
      concurrent symptoms of Rolandic epilepsy. She then had an atypical evolution with
      atypical absences, absence status epilepticus, atonic seizures and mild
      impairment of scholastic performance. The case emphasises the close links between
      Panayiotopoulos syndrome and Rolandic epilepsy, both of which probably represent
      different clinical phenotypes of a maturational-related benign childhood seizure
      susceptibility syndrome [published with videosequences].

PMID- 11967179
TI  - Postictal signs of lateralizing and localizing significance.
AB  - Epileptic seizures are followed by dynamic alterations in neurological function
      in the postictal period. Although the first observation of such phenomena dates
      back to Bravais who described postictal hemiparesis in 1827, this critical period
      of time after seizure offset has received little attention in the literature. In
      this article, we report some of the most important postictal signs, such as
      postictal hemiparesis, postictal nose wiping, postictal language dysfunction,
      postictal headache and postictal cognitive impairment. Summarizing our own
      experience of the postictal state in more than 160 patients with focal epilepsy,
      we conclude that postictal signs can provide reliable information for the
      localization of the seizure onset zone in patients with focal epilepsy. Since the
      lateralization and localization of the seizure onset zone has become a major
      issue for the presurgical evaluation of those patients, we argue that more
      attention should be paid to the postictal state during video EEG monitoring.
      Moreover, in an ambulatory setting, the postictal period and its related signs is
      usually the only part of an epileptic seizure that is accessible to the
      physician's examination and might therefore add some information to the
      differential diagnosis of paroxysmal events, such as epileptic or psychogenic
      seizures [published with videosequences].

PMID- 11967180
TI  - Prospective study on concentration-efficacy and concentration-toxicity:
      correlations with lamotrigine serum levels.
AB  - RATIONALE: The relationship between lamotrigine (LTG) serum concentration and
      clinical response in patients with epilepsy is still controversial. We therefore
      performed a prospective study in which LTG was added to the existing therapeutic
      regimen in patients with poorly controlled epilepsy. The goal of the study was to
      determine the serum levels of patients with seizure reduction of at least 50%
      after addition of LTG, and to assess a possible relationship between the
      occurrence of adverse effects due to LTG and its serum concentration. METHODS:
      Fifteen adult patients were evaluated with respect to seizure reduction. Nine
      patients had focal seizures with or without generalization, six patients had
      generalized seizures (Group I). The correlation between the occurrence of adverse
      effects and LTG serum concentration was calculated in a second group of 63 young
      adult, and adult patients with epilepsy (Group II). RESULTS: The range of the LTG
      serum concentration in the 15 patients with a 50% or greater reduction of seizure
      frequency was 1.3-7.1 microg/ml (median = 3.6 microg/ml). In group II patients
      the serum concentration associated with an adverse effect was not significantly
      different from the serum concentration in patients without adverse effects. There
      was, however, a tendency for higher serum concentrations in patients with adverse
      effects. In the serum concentration range of 5 to 13 microg/ml, the frequency of
      LTG levels which were accompanied by an adverse effect increased only slowly,
      whereas above 13-14 microg/ml, there was a steep increase in adverse effects. The
      serum concentration of four patients with tremor (mean = 14 +/- 2.8 microg/ml)
      was significantly higher than the LTG level which were in 42 patients who did not
      have adverse effects at any time (mean = 4.8 +/- 4.1 microg/ml), P = 0.003.
      CONCLUSION: Our results suggest a target range for LTG serum concentrations of 1
      13 microg/ml, especially, if LTG is used as an add on-drug.

PMID- 11967181
TI  - Comparison, characterization, and identification of proteases and protease
      inhibitors in epididymal fluids of domestic mammals. Matrix metalloproteinases
      are major fluid gelatinases.
AB  - The testicular and epididymal fluids of ram, boar, and stallion were analyzed by
      means of one-dimensional and two-dimensional gelatin gel zymography. Five main
      gelatinolytic bands were revealed in the ram and at least seven were observed in
      the boar and stallion. These proteolytic bands showed regionalized distribution
      throughout the organs. The two main proteolytic activities at around 54-66 kDa
      retrieved in all three species were inhibited by EDTA and phenanthroline,
      indicating that they were metallo-dependent enzymes. The activity of some of the
      low-molecular-weight gelatinases was also decreased by EDTA, whereas others were
      inhibited by serine protease inhibitors. One of the main proteases at 60-62 kDa
      from the caput fluid of the stallion and the ram was N-terminal sequenced; in
      both cases, high sequence homology was found with the N-terminal of the matrix
      metalloproteinase-2 pro-form (pro-MMP-2). Antibodies against MMP-2, MMP-3, and
      MMP-9 gelatinases confirmed the regional distribution in the fluids of pre -, pro
      , active, or degraded forms of these metalloproteases in all three species. We
      also observed the presence of acrosin in epididymal fluids, which was probably
      released by dead spermatozoa, but this enzyme did not explain all the serine
      protease activity. Moreover, the majority of this enzyme is bound to the protease
      inhibitor alpha(2)-macroglobulin, which is present in the fluids of all three
      species. TIMP-2, a potent inhibitor of MMPs, was present in the fluid of the
      caput regions in the ram and boar, and in the caput and caudal fluids of the
      stallion. This study demonstrated that similar types of proteases and inhibitors
      are regionally distributed in the epididymal fluids of three domestic species,
      suggesting an identical role in the sperm maturation process, the plasticity of
      this organ, or both.

PMID- 11967182
TI  - Oxytocin receptor regulation and action in a human granulosa-lutein cell line.
AB  - Although oxytocin and its receptor have been identified in human ovary, its
      regulatory role in granulosa cell or corpus luteum function has not been clearly
      defined. To better understand oxytocin action in the human ovary, we have
      characterized the expression and function of oxytocin receptors in an
      immortalized human granulosa-lutein cell line, HGL5. Expression of oxytocin
      receptor mRNA was demonstrated by reverse transcriptase-polymerase chain reaction
      analysis, and by specific binding of an iodinated oxytocin antagonist (apparent
      dissociation constant of 131 +/- 0.15 pM, and a B(max) of 12 +/- 0.5 fmol/microg
      DNA). Receptor levels were down-regulated by serum starvation, and rapidly up
      regulated by serum restoration. Stimulation of protein kinase C activity
      increased oxytocin receptor levels in a concentration-dependent manner.
      Conversely, protein kinase C inhibition blocked up-regulation of oxytocin
      receptors. Treatment of cells with 10 nM oxytocin resulted in a rapid, transient
      increase in intracellular Ca(2+), and the response was blocked by an oxytocin
      antagonist. Because HGL5 cells secrete progesterone and estradiol in response to
      agents that elevate intracellular cAMP concentrations, we studied the effect of
      oxytocin on steroid production. Oxytocin enhanced the effects of forskolin on
      progesterone production. These results suggest that oxytocin augments the
      activity of luteotropins in vivo. Our studies are the first to show an ovarian
      cell line that expresses functional oxytocin receptors. These cells can serve as
      a useful model for studying oxytocin signal pathways and their cross-talk with
      respect to progesterone synthesis. These cells also will be useful in the
      analysis of mechanisms of oxytocin receptor regulation, including regulation of
      its gene.

PMID- 11967183
TI  - Up-regulation of mesotocin receptors in the tammar wallaby myometrium is
      pregnancy-specific and independent of estrogen.
AB  - The oxytocin-like peptide of most Australian marsupials is mesotocin, which
      stimulates uterine contractions and is important for normal birth in the tammar
      wallaby. Female marsupials have two uteri and, in monovular species such as the
      tammar, one uterus is gravid with a single fetus, whereas the contralateral
      uterus is nongravid. A significant increase in myometrial mesotocin receptor
      concentrations occurs only in the gravid uterus on Day 23 of the 26-day
      gestation. This study examined whether or not mesotocin receptors are present in
      the myometrium and are up-regulated at the equivalent stage of the luteal phase
      in unmated tammars. In contrast to the marked increase in mesotocin receptor mRNA
      and protein concentrations in the myometrium of the gravid uterus during
      pregnancy, receptors did not increase in the unmated animals. There were also no
      significant differences between the two uteri, except on Day 27. Plasma profiles
      of peripheral estradiol-17beta and progesterone did not differ significantly
      between pregnant and nonpregnant cycles. However, progesterone concentrations
      were significantly lower on Day 1 postpartum compared with Day 27 of the
      nonpregnant cycle. In pregnant tammars, the molar ratio of circulating estradiol
      17beta to progesterone increased significantly between Day 25 of gestation and 1
      day postpartum, but was not correlated with an increase in mesotocin receptor
      concentrations in either uterus. The data confirm that a local fetal influence is
      more important than systemic factors, such as estrogen, in the regulation of
      uterine mesotocin receptors in the tammar wallaby.

PMID- 11967184
TI  - Ultrastructural characteristics of fresh and frozen-thawed ovine embryos using
      two cryoprotectants.
AB  - Cryopreservation of sheep embryos with ethylene glycol as a protectant appears to
      be more effective than glycerol, particularly at the morula stage, as has been
      demonstrated on the basis of in vitro and in vivo development rates after
      thawing. In this study we compare the ultrastructure of fresh morulae, thawed
      morulae, and blastocysts cryopreserved with either ethylene glycol or glycerol at
      the electron microscopic level, to look for cellular damage that could be
      responsible for proven differences in embryo survival after transfer. Embryos
      cryopreserved with glycerol showed unequal degrees of conservation even among
      blastomeres within a single embryo. In morulae, inner blastomeres were completely
      damaged, whereas external ones appeared to be intact. Both morulae and
      blastocysts cryopreserved with ethylene glycol showed a higher uniformity in
      blastomere conservation than embryos with glycerol. The most remarkable features
      in this experimental group were the presence of desmosomes following tight
      junctions between blastomeres and the presence of many microvilli on the outer
      surface of external blastomeres. These characteristics are similar in fresh
      embryos of the control group. Our results show that ethylene glycol protects
      membrane and cytoplasmic structures of embryonic cells from cryoinjury much
      better than glycerol. In vivo survival of embryos confirmed the ultrastructural
      observations. A limited permeability of glycerol would explain the observed
      ultrastructural differences in blastomere integrity, which depends on blastomere
      location and the differences between morulae and blastocysts. We conclude that
      the low reproductive yield after cryopreservation using glycerol can be
      attributed to the lack of protection of inner cells.

PMID- 11967185
TI  - Golgi apparatus dynamics during mouse oocyte in vitro maturation: effect of the
      membrane trafficking inhibitor brefeldin A.
AB  - We have studied Golgi apparatus dynamics during mouse oocyte in vitro maturation,
      employing both live imaging with the fluorescent lipid BODIPY-ceramide and
      immunocytochemistry using several specific markers (beta-COP, giantin, and
      TGN38). In germinal vesicle oocytes the Golgi consisted of a series of
      structures, possibly cisternal stacks, dispersed in the ooplasm, but slightly
      more concentrated in the interior than at the cortex. A similar pattern was
      detected in rhesus monkey germinal vesicle oocytes. These "mini-Golgis" were
      functionally active because they were reversibly disrupted by the membrane
      trafficking inhibitor brefeldin A. However, the drug had no visible effect if the
      oocytes had been previously microinjected with GTP-gamma-S. During in vitro
      maturation the large Golgi apparatus structures fragmented at germinal vesicle
      breakdown, and dispersed homogenously throughout the ooplasm, remaining in a
      fragmented state in metaphase-II oocytes. Similarly to what has been reported
      using protein synthesis inhibitors, the presence of brefeldin A blocked
      maturation at the germinal vesicle breakdown stage before the assembly of the
      metaphase-I spindle. These results suggest that progression of murine oocyte
      maturation may require functional membrane trafficking.

PMID- 11967186
TI  - Estradiol modulation of growth hormone secretion in the ewe: no growth hormone
      releasing hormone neurons and few somatotropes express estradiol receptor alpha.
AB  - Evidence suggests that estrogen modulates growth hormone (GH) release and that GH
      plays an important role in follicular and ovulatory processes. How estradiol
      affects GH secretion is unclear. Having verified that there is a coincident surge
      of GH at the time of the preovulatory LH surge, immunocytochemical studies
      incorporating high-temperature antigen retrieval were used to determine whether
      GH-releasing hormone (GHRH) neurons, somatotropes, or both, expressed estrogen
      receptor alpha (ER), in the ewe. Although GHRH neurons were surrounded by many ER
      cells, they did not express immunocytochemically detectable ERs. In contrast to
      gonadotropes, in which the majority expressed ERs, few somatotropes were estrogen
      receptive. These data suggest that estrogen does not act directly on GHRH neurons
      to influence GH secretion, and any direct effect on pituitary GH release, through
      the ERalpha, may be small.

PMID- 11967187
TI  - Regulation of translation during in vitro maturation of bovine oocytes: the role
      of MAP kinase, eIF4E (cap binding protein) phosphorylation, and eIF4E-BP1.
AB  - Meiotic maturation of mammalian oocytes (transition from prophase I to metaphase
      II) is accompanied by complex changes in the protein phosphorylation pattern. At
      least two major protein kinases are involved in these events; namely, cdc2 kinase
      and mitogen-activated protein (MAP) kinase, because the inhibition of these
      kinases arrest mammalian oocytes in the germinal vesicle (GV) stage. We show that
      during meiotic maturation of bovine oocytes, the translation initiation factor,
      eIF4E (the cap binding protein), gradually becomes phosphorylated. This
      substantial phosphorylation begins at the time of germinal vesicle breakdown
      (GVBD) and continues to the metaphase II stage. The onset of eIF4E
      phosphorylation occurs in parallel with a significant increase in overall protein
      synthesis. However, although eIF4E is nearly fully phosphorylated in metaphase II
      oocytes, protein synthesis reaches only basal levels at this stage, similar to
      that of prophase I oocytes, in which the factor remains unphosphorylated. We
      present evidence that a specific repressor of eIF4E, the binding protein 4E-BP1,
      is present and could be involved in preventing eIF4E function in metaphase II
      stage oocytes. Recently, two protein kinases, called Mnk1 and Mnk2, have been
      identified in somatic cells as eIF4E kinases, both of which are substrates of MAP
      kinase in vivo. In bovine oocytes, a specific inhibitor of cdk kinases,
      butyrolactone I, arrests oocytes in GV stage and prevents activation of both cdc2
      and MAP kinase. Under these conditions, the phosphorylation of eIF4E is also
      blocked, and its function in initiation of translation is impaired. In contrast,
      PD 098059, a specific inhibitor of the MAP kinase activation pathway, which
      inhibits the MAP kinase kinase, called MEK function, leads only to a postponed
      GVBD, and a delay in MAP kinase and eIF4E phosphorylation. These results indicate
      that in bovine oocytes, 1) MAP kinase activation is only partially dependent on
      MEK kinase, 2) MAP kinase is involved in eIF4E phosphorylation, and 3) the
      abundance of fully phosphorylated eIF4E does not necessarily directly stimulate
      protein synthesis. A possible MEK kinase-independent pathway of MAP kinase
      phosphorylation and the role of 4E-BP1 in repressing translation in metaphase II
      oocytes are discussed.

PMID- 11967188
TI  - Production of cloned pigs from cultured fetal fibroblast cells.
AB  - Somatic cell nuclear transfer was used to produce live piglets from cultured
      fetal fibroblast cells. This was achieved by exposing donor cell nuclei to oocyte
      cytoplasm for approximately 3 h before activation by chemical means. Initially,
      an experiment was performed to optimize a cell fusion system that prevented
      concurrent activation in the majority of recipient cytoplasts. Cultured
      fibroblast cells were fused in medium with or without calcium into enucleated
      oocytes flushed from superovulated gilts. Cybrids fused in the presence of
      calcium cleaved at a significantly (P < 0.05) greater rate (69%, 37 out of 54)
      after 2 days of culture compared with those fused without calcium (10%, 7 out of
      73), suggesting that calcium-free conditions are needed to avoid activation in
      the majority of recipient cytoplasts during fusion. In the second experiment,
      cybrids fused in calcium-free medium were activated approximately 3 h later with
      ionomycin, followed by incubation in 6-dimethylaminopurine to determine
      development in vitro. Following 2 days of culture, cleavage rates of chemically
      activated and unactivated cybrids (fusion without activation control) were 93%
      (100 out of 108) and 7% (2 out of 27), respectively. After an additional 5 days
      of culture, activated cloned embryos formed blastocysts at a rate of 23% (25 out
      of 108) with an average inner cell mass and trophectoderm cell number of 10
      (range, 3 to 38) and 31 (range, 16 to 58), respectively. In the third experiment,
      activated nuclear transfer embryos were transferred to the uteri of synchronized
      recipients after 3 days of culture to assess their development in vivo. Of 10
      recipients receiving an average of 80 cleaved embryos (range, 40 to 107), 5
      became pregnant (50%) as determined by ultrasound between Day 25 and Day 35 of
      gestation. Of the five pregnant recipients, two subsequently farrowed one piglet
      per litter originating from two different cell culture lines. In this study,
      efficient reprogramming of porcine donor nuclei by fusing cells in the absence of
      calcium followed by chemical activation of recipient cytoplasts was reflected in
      high rates of development to blastocyst and pregnancy initiation leading to full
      term development.

PMID- 11967189
TI  - In vitro development of horse oocytes reconstructed with the nuclei of fetal and
      adult cells.
AB  - This study investigated the basic conditions required for the production of horse
      embryos by the transfer of the nuclei of fetal and adult fibroblast cells to
      enucleated oocytes. Cumulus-oocyte complexes were recovered from abattoir ovaries
      and matured in vitro in groups of 20-30 for 28-30 h in tissue culture medium 199
      containing 20% v:v fetal bovine serum in coculture with equine oviduct epithelial
      cells. Fetal fibroblast cells (FFC) were derived from a 32-day-old Thoroughbred x
      Pony fetus, and adult skin fibroblast cells (SFC) were obtained from subdermal
      biopsies recovered from a 4-yr-old female Pony. The rates of fusion between the
      recipient cytoplasm with either FFC or SFC were significantly greater when the
      cells were treated with a combination of direct current (DC) pulses and Sendai
      virus rather than with DC pulses alone (81%-82% vs. 49%-57%, P < 0.05). There
      were no differences in the rates of nuclear reprogramming between FFC and SFC
      (88% vs. 84%), but the rate of cleavage of the resulting embryos to the 2-cell
      stage was higher when FFC were used (53%) than when SFC were used (35%).
      Blastocysts were obtained from oocytes reconstructed with both types of donor
      cells and after culture in vitro for 6-7 days, but the overall proportion of
      blastocysts produced was very low in both cases (FFC, 4%; SFC, 7%). These results
      demonstrate a very limited potential for in vitro development of horse embryos
      after nuclear reprogramming following the transfer of nuclei from either fetal or
      adult fibroblasts into recipient enucleated oocytes.

PMID- 11967190
TI  - Age-related changes of the somatotropic axis in cloned Holstein calves.
AB  - To determine if the development of the somatotropic axis in somatic clones
      (clones) is similar to that in heifers produced by artificial insemination
      (controls), serum samples were collected every 30 min for 6 h, once per month,
      for 7 mo from 4 clones generated from a 13-yr-old cow and from 4 age-matched
      controls. Average concentrations of growth hormone (GH) were not different
      between clones and controls, and GH concentrations declined over time in
      controls. Average concentrations of insulin-like growth factor I (IGF-I) were
      less in clones than controls, and IGF-I concentrations increased over time in
      both groups. Concentrations of IGF-binding protein 3 (IGFBP-3) were greater in
      controls than in clones and did not change over time. Average IGFBP-2
      concentrations did not change over time and were not different between clones and
      controls. Clones and controls were challenged with GH-releasing hormone (GHRH) (3
      microg/100 kg body weight) and somatostatin (somatotropin release-inhibiting
      factor [SRIF]) (1.87 and 5 microg/100 kg body weight) at 14 mo of age. GHRH
      induced GH secretion was greater and SRIF inhibition of GHRH-induced GH was less
      in clones than in controls. We speculate that some of the differences between
      clones and controls in concentrations of GH, IGF-I, and IGFBP-3 may be related to
      the genetic merit of the animals. Although there were differences in
      concentrations of components of the somatotropic axis between these clones and
      their age-matched controls, the values recorded were all within the range
      reported for calves of similar ages.

PMID- 11967191
TI  - Sequence analysis and expressional regulation of messenger RNAs encoding beta
      subunits of follicle-stimulating hormone and luteinizing hormone in the red
      bellied newt, Cynops pyrrhogaster.
AB  - Two distinct cDNAs encoding beta subunits of follicle-stimulating hormone (FSH)
      and luteinizing hormone (LH) were cloned from the cDNA library constructed for
      the pituitary of the red-bellied newt, Cynops pyrrhogaster, and sequenced. The
      newt FSHbeta and LHbeta cDNAs encode polypeptides of 129 and 131 amino acids,
      including signal peptides of 20 and 19 amino acids, respectively. The number and
      position of cysteine and N-glycosylation in each of the beta subunits of FSH and
      LH, which are considered essential for assembly of the alpha subunit, are well
      conserved between the newt and other tetrapods. The high homology (41.6%) between
      the beta subunits of newt FSH and LH imply less specificity of FSH and LH in
      gonadal function. One cDNA encoding the common polypeptide chain alpha subunit of
      FSH and LH was also isolated from the newt pituitary gland. The mRNAs of FSHbeta,
      LHbeta, and the alpha subunit were expressed only in the pituitary gland among
      various newt tissues. Double-staining with in situ hybridization and
      immunohistochemistry revealed coexpression of FSHbeta and LHbeta in the same newt
      pituitary cells. Ovariectomy induced a significant increase in FSHbeta mRNA
      levels, but there was no significant change in LHbeta or alpha subunit mRNA
      levels compared with those in control animals. Taken together, these data suggest
      that two kinds of gonadotropins, namely FSH and LH, are expressed in the same
      gonadotropin-producing cells in the pars distalis of the newt as well as in other
      tetrapods and that the expression of FSHbeta is negatively regulated by the
      ovaries.

PMID- 11967192
TI  - Ovarian expression of messenger RNA encoding the receptors for luteinizing
      hormone and follicle-stimulating hormone in a marsupial, the brushtail possum
      (Trichosurus vulpecula).
AB  - Both LH and FSH play a central role in controlling ovarian function in mammals.
      However, little is known about the type of ovarian cells that are responsive to
      LH and FSH in marsupials. We determined, using in situ hybridization, the
      localization of mRNA encoding the receptors (R) for LH and FSH in ovaries of
      brushtail possums. The mRNA encoding FSH-R was observed in granulosa cells of
      healthy follicles containing at least two complete layers of cells. The mRNA
      encoding LH-R was first observed in granulosa cells at the time of antrum
      formation. Cells of the theca interna expressed LH-R mRNA but not FSH-R mRNA.
      Neither FSH-R nor LH-R mRNA was detected in atretic follicles. Both FSH-R and LH
      R mRNAs were observed in luteal tissue, but only LH-R mRNA was observed in
      interstitial cells. Granulosa cells from follicles of various sizes (0.5 to >2 mm
      in diameter) responded to LH and FSH treatment with an increase in cAMP
      synthesis. In contrast, luteal tissue did not respond to either FSH or LH
      treatment. In conclusion, expression of FSH-R in the brushtail possum ovary was
      similar to that observed in many eutherian mammals. However, active LH-R was
      expressed in granulosa cells much earlier in follicular development than has been
      previously observed. In addition, although mRNAs for both FSH-R and LH-R were
      observed, neither FSH nor LH treatment stimulated cAMP synthesis in luteal
      tissue.

PMID- 11967193
TI  - Carp ovarian cystatin binds and agglutinates spermatozoa via electrostatic
      interaction.
AB  - A sperm-agglutinating factor was purified from ovulated carp eggs and the
      conditioned medium (CM) of cortical-reacted eggs. It was identified to be the
      carp ovarian cystatin. Three cystatin isoforms were found. The cystatin isolated
      from the CM had a higher sperm-agglutinating activity than that isolated from
      eggs, although the cystatins have identical N-terminal amino acid sequences,
      masses, and positive charges. Differences in sperm-agglutinating activity between
      the cystatins of the CM and eggs may be caused by the different conformations
      because they differed in circular dichroism spectrum and tryptic map. Cystatin
      was discharged from cortical granules to the perivitelline space after
      fertilization and is abundant in the perivitelline fluid (PVF) of early stage
      embryos. Cystatin rapidly agglutinated spermatozoa via an electrostatic
      interaction. Other basic proteins also agglutinated carp spermatozoa. Their
      activities were inhibited by salt and high pH. Cystatin bound to the entire
      surface of carp spermatozoa. The PVF of early embryos agglutinated carp
      spermatozoa. The activity was related to the cystatin content and influenced by
      ionic strength and pH. Therefore, cystatin is the major sperm-agglutinating
      factor of PVF. Owing to the rapid action of cystatin on spermatozoa agglutination
      and the presence of a high concentration of cystatin in PVF, cystatin is
      considered important for preventing polyspermy in carp eggs.

PMID- 11967194
TI  - Mouse sperm cell-specific DnaJ first homologue: an evolutionarily conserved
      protein for spermiogenesis.
AB  - Msj-1 (mouse sperm cell-specific DnaJ first homologue) is a gene specifically
      expressed in germ cells at haploid stages. The protein first appears in round
      spermatids, accumulates in the periacrosomal region of elongating spermatids, and
      is maintained in spermatozoa. The msj-1 expression pattern is consistent with a
      role for this DnaJ protein in the spermiogenesis process. In this study, we used
      two experimental models, the anuran amphibian Rana esculenta and the wobbler
      mutant mouse, to explore the role of MSJ-1 during spermatogenesis, with a focus
      on spermiogenesis. Mice homozygous for the recessive mutation wobbler (wr/wr), a
      mutation of unknown identity, produce sperm cells characterized by a missing
      acrosome. In Rana esculenta testis, detection of high levels of MSJ-1 protein
      coincided with the appearance of postmeiotic germ cells during the annual sexual
      cycle. Conversely, elimination of the meiotic and postmeiotic stages, through
      gonadotropin administration at low temperature, abolished the MSJ-1
      immunoreactive signal. In 20-day-old mice, when postmeiotic germ cells appeared
      for the first time, MSJ-1 mRNA and protein were observed in +/+ testis but were
      barely detectable in wr/wr testis. In adult testis, reduced MSJ-1 protein levels
      were observed in both +/wr and wr/wr testis, as compared with +/+ controls.
      Similarly, numbers of spermatids that stained by immunofluorescence for MSJ-1
      appeared to be progressively reduced in adult +/+, +/wr, and wr/wr mouse testes,
      respectively. Characterization of the endocrine status of wobbler testis revealed
      reduced transcript levels of estrogen receptor alpha and reduced intratesticular
      androgen levels. However, androgen treatment did not affect MSJ-1 protein levels
      in either frogs or mice. In conclusion, our data in Rana esculenta and the
      wobbler mouse demonstrate a tight correlation between MSJ-1 protein expression
      and postmeiotic stages. In particular, the findings in the wobbler testis suggest
      a role for this protein in acrosomogenesis.

PMID- 11967196
TI  - Hypertonic medium treatment for localization of nuclear material in bovine
      metaphase II oocytes.
AB  - Oocytes enucleated at the second metaphase stage (MII) are often used as
      recipient cytoplasts for nuclear transfer. The oocyte's nuclear material has been
      traditionally removed blindly by aspirating the first polar body (Pb1) along with
      a portion of the cytoplasm. However, the Pb1-guided enucleation method is
      unreliable because the position of the Pb1 is variable. A previous study showed
      that pretreatment of mouse oocytes with 3% (0.09 M) sucrose allowed visualization
      of the metaphase spindle and chromosomes under standard light microscopy and led
      to a 100% enucleation rate. The same sucrose treatment, however, did not produce
      the same effect in bovine oocytes. In this study, we increased the concentration
      of sucrose to 0.3-0.9 M in PBS containing 20% fetal bovine serum (SPF) and found
      that the majority of the treated bovine oocytes (75%-86%) formed a small
      transparent bud into the perivitelline space, as compared with the 0.1 M sucrose
      (6%) or the no sucrose (0%) control groups. Staining of DNA with Hoechst 33342
      revealed that these projections coincided with the position of the metaphase
      chromosomes in 100% of sucrose-treated oocytes, whereas only 31% of oocytes
      showed alignment of the position of Pb1 with their nuclear materials.
      Furthermore, 95% of oocytes treated in 0.3 M SPF were successfully enucleated by
      removing a small amount of cytoplasm adjacent to the projection. This is a
      significantly higher enucleation rate than that obtained by conventional Pb1
      guided enucleation, even when a larger amount of cytoplasm was removed. For
      nuclear transfer, the enucleated oocytes treated with sucrose did not differ from
      the control oocytes in rates of fusion, cleavage, or development to blastocysts,
      or in the average cell numbers in blastocysts. This study demonstrated that 0.3 M
      sucrose treatment of bovine oocytes facilitates the localization of metaphase
      chromosomes under normal light microscopy and hence increases enucleation
      efficiency without compromising the in vitro development potential of cloned
      embryos by nuclear transfer.

PMID- 11967195
TI  - 25-hydroxycholesterol is produced by testicular macrophages during the early
      postnatal period and influences differentiation of Leydig cells in vitro.
AB  - Leydig cells develop inappropriately in animals lacking testicular macrophages.
      We have recently found that macrophages from adult animals produce 25
      hydroxycholesterol, an oxysterol involved in the differentiation of hepatocytes
      and keratinocytes. Therefore, we hypothesized that testicular macrophages also
      produce 25-hydroxycholesterol during the early postnatal period and that this
      oxysterol plays a role in the differentiation of Leydig cells. We assessed the
      production of 25-hydroxycholesterol and 25-hydroxylase mRNA by cultured
      testicular macrophages from rats at 10, 20, and 40 days of age. We also tested
      the long-term effects of 25-hydroxycholesterol on basal and LH-stimulated
      testosterone production, and 3beta-hydroxysteroid dehydrogenase activity as end
      points of Leydig cell differentiation in vitro. We found that testicular
      macrophages from animals at all ages produced both 25-hydroxycholesterol and 25
      hydroxylase mRNA, with macrophages from 10-day-old animals having the highest
      steady-state levels of message. We also found that chronic exposure of Leydig
      cells to 25-hydroxycholesterol increased basal production of testosterone but
      decreased LH-stimulated steroidogenesis at all ages. Finally, 25
      hydroxycholesterol increased 3beta-hydroxysteroid dehydrogenase activity in both
      progenitor and immature Leydig cells. These findings support the hypothesis that
      testicular macrophages play an important role in the differentiation of Leydig
      cells through the secretion of 25-hydroxycholesterol.

PMID- 11967197
TI  - Thrombin generation and presence of thrombin receptor in ovarian follicles.
AB  - Prothrombin, once converted to its enzymatically active form (i.e., thrombin),
      induces a broad spectrum of cellular responses in both vascular and avascular
      tissues. Bovine ovarian granulosa cells isolated from healthy follicles of
      various sizes contain both prothrombin mRNA and immunologically reactive
      prothrombin that appears to be identical to prothrombin in follicular fluid and
      plasma. When tissue factor, the primary physiological activator of thrombin
      generation in plasma, is used to initiate thrombin formation, the profile of
      prothrombin-to-thrombin conversion is similar in follicular fluid and plasma. The
      conclusion that biologically functional prothrombin is synthesized by granulosa
      cells is further supported by evidence that mRNA for gamma-glutamyl carboxylase,
      an enzyme essential for the vitamin K-dependent posttranslational modification of
      prothrombin, is expressed in granulosa cells in a manner similar to prothrombin
      mRNA. Thrombin's biological effects are mediated through selective proteolytic
      cleavage and activation of specific receptors. Bovine granulosa cells possess
      thrombin receptor (PAR-1) mRNA, and as seen with prothrombin mRNA and gamma
      glutamyl carboxylase mRNA, cells isolated from small follicles possess more PAR-1
      mRNA than cells from large follicles. Thrombin receptor expression by cells in
      close proximity to an active thrombin-generating system suggests that these
      factors may be important mediators of cellular function in the ovarian follicle.

PMID- 11967198
TI  - Changes in the testis interstitium of Brown Norway rats with aging and effects of
      luteinizing and thyroid hormones on the aged testes in enhancing the
      steroidogenic potential.
AB  - We tested the possibility of using LH and thyroxine (T(4)) to restore the
      testicular steroidogenic ability in aged Brown Norway rats. Three-, 6-, 12- (n =
      8 per group), and 18-mo-old (n = 32; 3M, 6M, 12M, and 18M, respectively) rats
      were used. The 18M rats were divided into four groups (n = 8 per group) and
      implanted subdermally with Alzet mini-osmotic pumps containing saline (control),
      LH (24 microg/day), T(4) (5 microg/day), and LH+T(4) (24+5 microg/day),
      respectively, for 4 wk (to 19 mo [19M] of age). Testis volume and absolute
      volumes of many testicular components were unchanged with advancing age and
      treatments, except for the blood vessels (occasional thickening), lymphatic space
      (increased), and Leydig cells (decreased with age but increased to the 3M level
      with LH and to the 12M level with both T(4) and LH+T(4), respectively). The
      number of Leydig and connective tissue cells per testis was unchanged with aging
      and treatments. The number of macrophages was significantly higher in treated
      rats. The average volume of a Leydig cell was significantly decreased in 12M and
      19M control rats. However, LH and LH+T(4) restored it to the 3M level, and T(4)
      restored to the 12M level. The steroidogenic ability of Leydig cells in vitro
      decreased when aging from the 3M to the 19M level, LH and T(4) enhanced it to the
      12M level, and LH+T(4) raised it to the 3M level. Serum LH was unchanged from 3M
      to 12M rats, significantly reduced in 19M control rats, and raised above the 3M
      values with both LH and LH+T(4) treatment and above the 19M (control) values with
      T(4) treatment; the latter values were lower than the 3M level. Serum T(4) and
      tri-iodothyronine (T(3)) were highest in 3M and 6M rats and declined in 12M and
      19M control rats; the latter group had the lowest levels. In all treated groups,
      T(4) and T(3) levels were significantly above those of 19M control rats but were
      lower than those of 3M through 12M rats. Serum testosterone was unchanged from 3M
      to 12M rats but was reduced in 19M control rats. Both LH and T(4) significantly
      raised these values above the 19M control levels, but they were still lower than
      the 3M through 12M levels. Additionally, LH+T(4) significantly raised the serum
      testosterone levels to those of 12M rats, but these values were significantly
      lower than those of 3M and 6M rats. These findings show that with 24+5-microg
      dose of LH+T(4) per day for 4 wk, a 100% recovery of the average volume of a
      Leydig cell and its steroidogenic ability in vitro and a 73% and 300% restoration
      of serum testosterone levels compared to 3M and 19M control rats, respectively,
      could be achieved in aged Brown Norway rats. A 100% reversibility (compared to 3M
      rats) in serum testosterone levels appears to be possible with adjustments in the
      LH and T(4) doses in the LH+T(4) treatment.

PMID- 11967200
TI  - Biological activity and enrichment of spermatogonial stem cells in vitamin A
      deficient and hyperthermia-exposed testes from mice based on colonization
      following germ cell transplantation.
AB  - Spermatogenesis is a complex process in which spermatogonial stem cells divide
      and subsequently differentiate into spermatozoa. This process requires
      spermatogonial stem cells to self-renew and provide a continual population of
      cells for differentiation. Studies on spermatogonial stem cells have been limited
      due to a lack of unique markers and an inability to detect the presence of these
      cells. The technique of germ cell transplantation provides a functional assay to
      identify spermatogonial stem cells in a cell population. We hypothesized that
      vitamin A-deficient (VAD) and hyperthermically treated testes would provide an
      enriched in vivo source of spermatogonial stem cells. The first model,
      hyperthermic treatment, depends on the sensitivity of maturing germ cells to high
      temperatures. Testes of adult mice were exposed to 43 degrees C for 15 min to
      eliminate the majority of differentiating germ cells. Treated donor testes were
      50% of normal adult testis size and, when transplanted into recipients, resulted
      in a 5.3- and 19-fold (colonies and area, respectively) increase in colonization
      efficiency compared to controls. The second model, VAD animals, also lacked
      differentiating germ cells, and testes weights were 25% of control values.
      Colonization efficiency of germ cells from VAD testes resulted in a 2.5- and 6.2
      fold (colonies and area, respectively) increase in colonization compared to
      controls. Hyperthermically treated mice represent an enriched source of
      spermatogonial stem cells. In contrast, the low extent of colonization with germ
      cells from VAD animals raises important questions regarding the competency of
      stem cells from this model.

PMID- 11967199
TI  - Rhesus monkey embryos produced by nuclear transfer from embryonic blastomeres or
      somatic cells.
AB  - Production of genetically identical nonhuman primates would reduce the number of
      animals required for biomedical research and dramatically impact studies
      pertaining to immune system function, such as development of the human
      immunodeficiency-virus vaccine. Our long-term goal is to develop robust somatic
      cell cloning and/or twinning protocols in the rhesus macaque. The objective of
      this study was to determine the developmental competence of nuclear transfer (NT)
      embryos derived from embryonic blastomeres (embryonic cell NT) or fetal
      fibroblasts (somatic cell NT) as a first step in the production of rhesus monkeys
      by somatic cell cloning. Development of cleaved embryos up to the 8-cell stage
      was similar among embryonic and somatic cell NT embryos and comparable to
      controls created by intracytoplasmic sperm injection (ICSI; mean +/- SEM, 81 +/-
      5%, 88 +/- 7%, and 87 +/- 4%, respectively). However, significantly lower rates
      of development to the blastocyst stage were observed with somatic cell NT embryos
      (1%) in contrast to embryonic cell NT (34 +/- 15%) or ICSI control embryos (46 +/
      6%). Development of somatic cell NT embryos was not markedly affected by donor
      cell treatment, timing of activation, or chemical activation protocol. Transfer
      of embryonic, but not of somatic cell NT embryos, into recipients resulted in
      term pregnancy. Future efforts will focus on optimizing the production of somatic
      cell NT embryos that develop in high efficiency to the blastocyst stage in vitro.

PMID- 11967201
TI  - Conditions for in vitro maturation and artificial activation of ferret oocytes.
AB  - The ferret represents an attractive species for animal modeling of lung diseases
      because of the similarity between ferret and human lung biology and its
      relatively small size and short gestation time. In an effort to establish
      experimental protocols necessary for cloning ferrets, optimized conditions for in
      vitro maturation and artificial activation of ferret oocytes were examined.
      Cumulus-oocyte complexes were harvested from ovaries of superovulated ferrets,
      and in vitro maturation was evaluated in three different culture media: medium 1
      (TCM-199 + 10% FBS), medium 2 (TCM-199 + 10% FBS with eCG [10 IU/ml] and hCG [5
      IU/ml]), or medium 3 (TCM-199 + 10% FBS with eCG, hCG, and 17beta-estradiol [2
      microg/ml]). After 24 h of maturation in vitro, the maturation rate of oocytes
      cultured in medium 2 (70%, n = 79) was significantly greater (P < 0.01) than
      those of oocytes cultured in the other two media (27%-36%, n = 67-73). At 48 h,
      similar maturation rates (56%-69%, n = 76-87) were observed for all three types
      of media. For activation experiments, oocytes cultured in medium 2 were
      stimulated with electrical and chemical stimuli either individually or in
      combination. Treatment with cycloheximide and 6-dimethylaminopurine (6-DMAP)
      following electrical stimulation resulted in 43% (n = 58) of the oocytes
      developing to the blastocyst stage. Such an activation rate represented a
      significant improvement over those obtainable under other tested conditions,
      including individual treatment with electrical pulses (10%, n = 41),
      cycloheximide (3%, n = 58), or 6-DMAP (5%, n = 59). Blastocysts derived from in
      vitro activation appeared to be normal morphologically and were composed of an
      appropriate number of both inner cell mass (mean +/- SEM, 10.3 +/- 1.1; n = 11)
      and trophectoderm (60.8 +/- 2.9, n = 11) cells. These results have begun to
      elucidate parameters important for animal modeling and cloning with ferrets.

PMID- 11967202
TI  - Analysis of luteal tissue inhibitor of metalloproteinase-1, -2, and -3 during
      prostaglandin F(2alpha)-induced luteolysis.
AB  - Increased matrix metalloproteinase (MMP) expression and activities help to
      mediate tissue involution through increasing extracellular matrix remodeling and
      promoting dedifferentiation and, ultimately, apoptosis. Therefore, we
      hypothesized that prostaglandin (PG) F(2alpha) administration would decrease
      expression of the tissue inhibitor of metalloproteinase (TIMP)-1, -2, and -3 and
      effectively increase the MMP:TIMP ratio, leading to glandular involution. In
      experiment 1, we tested the effects of PGF(2alpha) administration (Day 10
      postestrus; Day 0 = estrus) on luteal TIMP-1, -2, and -3 mRNA and protein
      expression. Corpora lutea were collected at 0, 15, or 30 min or at 1, 2, 4, 6,
      12, 24, and 48 h following PGF(2alpha) administration (n = 3-9 animals/time
      point). Following PGF(2alpha) administration, TIMP-1 mRNA levels decreased (P <
      0.05) at 1 and 2 h relative to 0 h (controls), then increased to levels greater
      than controls at 4 and 6 h. In contrast, TIMP-2 and -3 mRNA levels did not
      decrease following PGF(2alpha) administration. The TIMP-1, -2, and -3 proteins
      were localized to large luteal cells (LLCs) within control (untreated) tissues.
      However, histodepletion of TIMP-1 within LLCs was evident within 30 min (earliest
      time point collected) following PGF(2alpha) injection and continued through 48 h.
      Luteal concentration of TIMP-1, as determined by RIA, was decreased (P < 0.05) by
      15 min (earliest time point collected) following PGF(2alpha) administration and
      remained low through 48 h. In contrast, TIMP-2 and -3 immunolocalization was not
      altered by PGF(2alpha) administration. Experiment 2 was conducted to determine if
      PGF(2alpha) could initiate the preceding changes in TIMP-1 in early (Day 3)
      corpora lutea that can bind PGF(2alpha) but are refractory to its luteolytic
      effects. Serum concentrations of progesterone and luteal concentrations of TIMP-1
      mRNA and protein were similar at 0 and 6 h after PGF(2alpha) injection on Day 3
      postestrus. These data suggest that an early and sustained effect of PGF(2alpha)
      is the specific depletion of TIMP-1 within LLCs that are capable of responding to
      the luteolytic action of PGF(2alpha). This action may increase the MMP:TIMP-1
      ratio, creating an environment that favors extracellular matrix degradation and,
      thereby, facilitates both functional and structural regression.

PMID- 11967203
TI  - Neuroendocrine control of follicle-stimulating hormone (FSH) secretion: II. Is
      follistatin-induced suppression of FSH secretion mediated via changes in activin
      availability and does it involve changes in gonadotropin-releasing hormone
      secretion?
AB  - The objective of the present study was to determine to what extent activin
      participates in setting the level of FSH secretion and if this regulation
      includes mediation via changes in GnRH secretion. We administered follistatin,
      the high-affinity binding protein for activin, to five ovariectomized sheep; we
      reasoned that the resultant binding of follistatin to activin should lower
      activin bioavailability and FSH secretion. Hypophyseal portal and peripheral
      blood samples were collected simultaneously at 10-min intervals for 18 h to
      measure GnRH, LH, FSH, and both activin-free and total follistatin. Six hours
      into collection, each ewe received 150 microg/kg i.v. of recombinant human
      follistatin-288. A week later, the same ewes were subjected to a second series of
      blood collections of similar length (time control). The FSH levels in pituitary
      portal blood were approximately 8-fold higher than those in the peripheral
      circulation. The FSH secretory patterns changed minimally during the time-control
      period. In contrast, follistatin had profound suppressive effects on FSH
      secretion. Maximal FSH suppression after FS-288 administration occurred at 5-6 h
      in the pituitary portal (65% suppression) and 9-10 h in the peripheral (48%
      suppression) circulation. Follistatin had no effect on GnRH or LH secretory
      patterns. Disappearance of total follistatin (i.e., free follistatin plus activin
      bound follistatin) from the circulation was slower (P < 0.05) than that of free
      follistatin alone, suggesting that some of the follistatin was complexed with
      circulating activin, thus reducing the bioavailability of activin. The slower
      clearance of total follistatin and the lack of follistatin effects on GnRH
      secretion suggest that changes in activin bioavailability dictate the level of
      pituitary FSH secretion and that this is a pituitary-specific effect.

PMID- 11967204
TI  - Functional significance of gap junctional coupling in preimplantation
      development.
AB  - Gap junctional intercellular coupling allows cells to share low molecular weight
      metabolites and second messengers, thus facilitating homeostatic and
      developmental processes. Gap junctions make their appearance very early in rodent
      development, during compaction in the eight-cell stage. Surprisingly,
      preimplantation mouse embryos lacking the gap junction protein connexin 43
      develop normally and establish full-term pregnancies despite severely reduced gap
      junctional coupling. It was suggested that this might be explained by the
      presence of at least five additional connexins known to be expressed in
      blastocysts. In the present study, we set out to clarify the number of connexins
      present in preimplantation rodent embryos and the role of gap junctional
      coupling, if any, in blastocyst development. We provide evidence from reverse
      transcription-polymerase chain reaction analysis that the genes encoding 3
      additional connexins (connexin 30 or beta6, connexin 36 or alpha9, and connexin
      57 or alpha10) are also transcribed in preimplantation mouse embryos.
      Furthermore, we show that multiple connexins are expressed in rat preimplantation
      embryos, indicating that multiplicity of connexin expression may be a common
      feature of early mammalian embryogenesis. We could detect no up-regulation of any
      of 3 coexpressed connexins examined in mouse embryos lacking connexin 43.
      Impaired intercellular coupling caused either by the loss of connexin 43 or by
      treatment of cultured embryos with the gap junctional coupling blocker 18alpha
      glycyrrhetinic acid (AGA) had no discernable effect on either apoptosis or
      glucose utilization, parameters known to be affected by gap junctional coupling
      in other contexts. These results, taken together with the reported inability of
      AGA to perturb blastocyst formation, imply that gap junctional coupling is not
      essential during this developmental period. We propose that connexin expression
      and the assembly of multiple types of gap junction channels in preimplantation
      embryos facilitates the diversification of communication pathways that will
      appear during postimplantation development. New evidence of this diversification
      is presented using rat blastocyst outgrowths.

PMID- 11967205
TI  - Gonadotropin surge-induced up-regulation of the plasminogen activators (tissue
      plasminogen activator and urokinase plasminogen activator) and the urokinase
      plasminogen activator receptor within bovine periovulatory follicular and luteal
      tissue.
AB  - This study examined the effect of the preovulatory gonadotropin surge on the
      temporal and spatial regulation of tissue plasminogen activator (tPA), urokinase
      plasminogen activator (uPA), and uPA receptor (uPAR) mRNA expression and tPA,
      uPA, and plasmin activity in bovine preovulatory follicles and new corpora lutea
      collected at approximately 0, 6, 12, 18, 24, and 48 h after a GnRH-induced
      gonadotropin surge. Messenger RNAs for tPA, uPA, and uPAR were increased in a
      temporally specific fashion within 24 h of the gonadotropin surge. Localization
      of tPA mRNA was primarily to the granulosal layer, whereas both uPA and uPAR
      mRNAs were detected in both the granulosal and thecal layers and adjacent ovarian
      stroma. Activity for tPA was increased in follicular fluid and the preovulatory
      follicle apex and base within 12 h after the gonadotropin surge. The increase in
      tPA activity in the follicle base was transient, whereas the increased activity
      in the apex was maintained through the 24 h time point. Activity for uPA
      increased in the follicle apex and base within 12 h of the gonadotropin surge and
      remained elevated. Plasmin activity in follicular fluid also increased within 12
      h after the preovulatory gonadotropin surge and was greatest at 24 h. Our results
      indicate that mRNA expression and enzyme activity for both tPA and uPA are
      increased in a temporally and spatially specific manner in bovine preovulatory
      follicles after exposure to a gonadotropin surge. Increased plasminogen activator
      and plasmin activity may be a contributing factor in the mechanisms of follicular
      rupture in cattle.

PMID- 11967206
TI  - Development of the stages of the cycle in mouse seminiferous epithelium after
      transplantation of green fluorescent protein-labeled spermatogonial stem cells.
AB  - To study the mechanism of male germ cell differentiation, testicular germ cells
      carrying green fluorescent protein (GFP) as a transgene marker were transplanted
      into infertile mouse testis. Fluorescence-positive seminiferous tubule segments
      colonized with GFP-labeled donor germ cells were isolated and measured, and
      differentiated germ cells were analyzed in living squashed preparations. Cell
      associations in normal stages of the seminiferous epithelial cycle were also
      studied and used as a reference. Two months after transplantation, the average
      length of the colonies was 1.3 mm. The cell associations of transplanted colonies
      were consistent with those of normal stages of the cycle. However, stages of the
      cycle were not necessarily identical in different colonies. Three months after
      transplantation, the average length of transplanted colonies was 3.4 mm, and the
      cell association in every portion of a colony was similar to that of the
      corresponding stage of the cycle. Even in long fused colonies made by
      transplantation of a higher concentration of male germ cells, the cell
      association patterns in various regions of a single colony were similar and
      consistent with those of some of the normal stages of the cycle. Development of
      different stages inside the colony was observed by 6 mo after transplantation.
      These results indicate that the commencement of spermatogonial stem cell
      differentiation occurs randomly to develop different stages of the cycle in
      different colonies. Then, each colony shows one single stage of the cycle for a
      long time, even if it becomes a very large colony or fuses with other colonies.
      These observations indicate the existence of some kind of synchronization
      mechanism. By 6 mo, however, normal development of the stages of the cycle
      appeared in seminiferous tubules.

PMID- 11967207
TI  - Implantation-associated changes in bovine uterine expression of integrins and
      extracellular matrix.
AB  - Appropriate integrin expression appears to be necessary for successful
      implantation of human embryos and varies considerably among species. The present
      study was undertaken to determine the distributions of integrin subunits
      alpha(1), alpha(3), and alpha(6) as well as the extracellular matrix (ECM)
      components collagen IV and laminin in implanting bovine trophoblast and
      endometrium. Immunohistochemical staining of cryostat sections prepared from
      nonpregnant endometrium, of preattachment through to early villus development
      pregnant endometrium (Days 18, 21, 24, and 30), and of isolated trophoblast
      binucleate cells was performed. Trophoblast down-regulated the integrin alpha(1)
      subunit as attachment proceeded, whereas reactivity scores for alpha(6) antibody
      tended to increase from Day 18 through 24 and remained high. A subpopulation of
      trophoblast binucleate cells expressed the alpha(3) integrin subunit. Uterine
      epithelium constitutively expressed alpha(3) and alpha(6) integrin subunits, but
      the alpha(1) subunit was down-regulated as the luminal epithelium was modified.
      Collagen IV and laminin reactivity increased in the basal lamina and underlying
      subepithelial stroma as pregnancy proceeded. The results suggest that binucleate
      cell fusion with the maternal epithelium initiates integrin and ECM changes in
      the subepithelial stroma.

PMID- 11967208
TI  - Osteopontin expression and regulation in the testis, efferent ducts, and
      epididymis of rats during postnatal development through to adulthood.
AB  - Osteopontin (OPN), a multifunctional phosphoprotein found in both hard and soft
      tissues, was examined in the male reproductive tract. The expression and
      regulation of OPN in the rat testis, efferent ducts, and epididymis was examined
      during postnatal development through to adulthood using immunocytochemistry at
      the light- and electron-microscopic level. Immunoblot analysis revealed a major
      30-kDa band for epididymal tissue and a major 60-kDa band for the testis. In the
      testis, immunostaining of OPN was noted in early germ cells from spermatogonia to
      early pachytene spermatocytes, suggesting a role for OPN as an adhesive protein
      binding these cells to the basement membrane and adjacent Sertoli cells.
      Nonciliated cells of the efferent ducts expressed OPN, whereas a cell- and region
      specific distribution of OPN was observed in the epididymis. Reactivity of OPN in
      the apical region of the cell corresponded to labeling of microvilli, small
      endocytic vesicles, and endosomes, where OPN may serve to remove calcium from the
      epididymal lumen and, thus, prevent mineral accumulation and subsequent decrease
      in sperm fertility. Regulation and postnatal studies revealed that circulating
      androgens regulate OPN expression in principal cells of the epididymis only.
      Taken together, the data reveal cell- and region-specific expression and
      regulation of OPN in the epididymis.

PMID- 11967209
TI  - Monozygotic twinning in rhesus monkeys by manipulation of in vitro-derived
      embryos.
AB  - The nonhuman primate is a relevant model for human disease that can be used for
      diverse biomedical investigations. The ability to propagate a founder animal by
      application of assisted reproductive technologies is pressing, but an even
      greater need in many studies is access to genetically identical animals. In an
      effort to create genetically identical monkeys, we evaluated two approaches to
      monozygotic twinning; blastomere separation, and blastocyst bisection. Embryos
      were produced by intracytoplasmic sperm injection of oocytes recovered following
      controlled ovarian stimulation. The quality of demiembryos produced in these
      efforts was evaluated by quantitating the efficiency of creating identical pairs
      for embryo transfer, by morphological assessment, by the allocation of cells to
      the inner cell mass (ICM) and trophectoderm (TE) in the blastocyst, and by the
      outcome of embryo transfer to synchronized host animals. Pairs were produced in
      high yield (85%-95%) by both twinning methods. Demiembryos resulting from
      blastomere separations at the 2- or 4-cell stage grew to blastocysts at the
      control frequency. Demiblastocysts contained, on average, half the number of
      cells of the intact controls while maintaining the same ICM:TE or ICM:total cell
      ratio. The equivalency of demiblastocysts within a set was also evaluated by
      differential cell counting. Embryo transfers of identical sets led to a 33%
      clinical pregnancy rate, with two twin pregnancies initiated. Neither pregnancy
      resulted in term birth of monozygotic twins, but our results are sufficiently
      encouraging to justify a large-scale twinning trial in the rhesus macaque.

PMID- 11967210
TI  - Fas is involved in the p53-dependent apoptotic response to ionizing radiation in
      mouse testis.
AB  - Apoptosis induced in male germ cells following ionizing radiation is dependent on
      functional p53 (Trp53) being present. We sought to determine whether Fas
      (Tnfrsf6/CD95/APO-1), an apoptotic factor, is involved in this p53-dependent germ
      cell death. In p53 knock-out mice exposed to 5 Gy of x-radiation, germ cells were
      protected from cell death, as assessed by counting apoptotic seminiferous tubules
      12 h following radiation. Similarly, spermatid head counts in p53 knock-out mice
      remained near normal 29 days after exposure to 0.5 Gy of radiation, whereas wild
      type animals had a more than twofold reduction in spermatid head counts. Fas mRNA
      expression remained at pretreatment levels in p53 knock-out mice; however, Fas
      increased in a time-dependent manner in wild-type mice following exposure to 5 Gy
      of radiation, indicating that radiation-induced Fas expression is p53-dependent.
      The functional significance of Fas involvement was demonstrated when lpr(cg)
      mice, having a nonfunctional Fas receptor, were exposed to 5 Gy of radiation; the
      number of apoptotic seminiferous tubules 12 h following radiation was
      significantly reduced compared to that of wild-type mice. Additionally, lpr(cg)
      mice exposed to 0.5 Gy of radiation had increased spermatid head counts 29 days
      following radiation compared to wild-type mice. Interestingly, gld mice with a
      non-functional Fas ligand (Tnfsf6/FasL/CD95L) were as sensitive to radiation as
      wild-type animals, and levels of FasL mRNA were not affected by radiation
      treatment. These results indicate that apoptosis and up-regulation of Fas
      following radiation are both p53-dependent events. Although Fas is necessary, in
      part, for radiation-induced p53-dependent apoptosis, FasL is not.

PMID- 11967211
TI  - Complementary DNA cloning and characterization of rat spergen-1, a spermatogenic
      cell-specific gene-1, containing a mitochondria-targeting signal.
AB  - To elucidate the molecular mechanisms involved with spermiogenesis in testis, we
      performed differential display screening to isolate genes that are
      developmentally up-regulated during rat testis development. One of the cDNAs
      isolated by differential display was highly expressed in testis. Both reverse
      transcription-polymerase chain reaction and Northern blot analysis showed that
      the expression level of the gene developmentally increased. By screening the rat
      testis cDNA library, we successfully isolated rat cDNA clones encoding the entire
      open-reading frame of 462 base pairs coding a small protein of 154 amino acids.
      Because in situ hybridization revealed that the gene was specifically expressed
      in haploid spermatids in the rat seminiferous tubules, it was designated as
      spergen-1 (spermatogenic cell-specific gene-1). The recently opened database of
      the full-length mouse cDNA collection contains a mouse gene that is homologous to
      rat spergen-1. Subcellular fractionation followed by immunoblot analysis revealed
      that spergen-1 protein was associated with mitochondria. The transfection
      experiments performed in COS-7 cells suggested that spergen-1 has a N-terminal
      mitochondria-targeting signal. We suggest that spergen-1 might be involved in
      spermiogenesis by transiently associating with spermatid mitochondria.

PMID- 11967212
TI  - Concurrent pregnancy retards mammary involution: effects on apoptosis and
      proliferation of the mammary epithelium after forced weaning of mice.
AB  - The effect of pregnancy on postweaning mammary gland involution was investigated
      in mice. On the third day after forced weaning at Lactation Day 10, the apoptotic
      index was 56% lower in mammary tissue of mice that were pregnant at the time of
      weaning than in nonpregnant mice. Conversely, the bromodeoxyuridine-labeling
      index was increased sevenfold in pregnant mice compared to nonpregnant controls
      (3.5% vs. 0.5%, respectively). Structure of mammary alveoli was largely
      maintained in postweaning pregnant mice. The effect of pregnancy on three
      specific mammary epithelial cell survival pathways was also examined. First,
      pregnancy blocked the loss of Stat5a phosphorylation during involution.
      Significantly, loss of Stat5a phosphorylation during involution was not
      correlated with loss of Stat5a nuclear localization. Second, pregnancy maintained
      nuclear-localized progesterone receptor during lactation. Third, pregnancy was
      associated with increased expression of bfl-1 during involution but had little
      effect on the expression of other bcl-2 family members. The data indicate that
      pregnancy inhibits mammary cell apoptosis after weaning while permitting
      proliferation of the mammary epithelium, and they support the hypothesis that
      Stat5a and progesterone-signaling pathways act in concert to mediate this effect.

PMID- 11967213
TI  - Effects of cooling and warming rate to and from -70 degrees C, and effect of
      further cooling from -70 to -196 degrees C on the motility of mouse spermatozoa.
AB  - We have previously reported high survival in mouse sperm frozen at 21 degrees
      C/min to -70 degrees C in a solution containing 18% raffinose in 0.25 x PBS (400
      mOsm) and then warmed rapidly at approximately 2000 degrees C/min, especially
      under lowered oxygen tensions induced by Oxyrase, a bacterial membrane
      preparation. The best survival rates were obtained in the absence of glycerol.
      The first concern of the present study was to determine the effects of the
      cooling rate on the survival of sperm suspended in this medium. The sperm were
      cooled to -70 degrees C at rates ranging from 0.3 to 530 degrees C/min. The
      survival curve was an inverted "U" shape, with the highest motility occurring
      between 27 and 130 degrees C/min. Survival decreased precipitously at higher
      cooling rates. Decreasing the warming rate, however, decreased survivals at all
      cooling rates. The motility depression with slow warming was especially evident
      in sperm cooled at the optimal rates. This fact is consistent with our current
      view that the frozen medium surrounding sperm cells is in a metastable state,
      perhaps partly vitrified as a result of the high concentrations of sugar. The
      decimation of sperm cooled more rapidly than optimum (>130 degrees C/min), even
      with rapid warming, is consistent with the induction of considerable quantities
      of intracellular ice at these rates. When glycerol was added to the above medium,
      motilities were also dependent on the cooling rate, but they tended to be
      substantially lower than those obtained in the absence of glycerol. The minimum
      temperature in the above experiments was -70 degrees C. When sperm were frozen to
      -70 degrees C at optimum rates, lowering the temperature to -196 degrees C had no
      adverse effect.

PMID- 11967214
TI  - Is intracellular ice formation the cause of death of mouse sperm frozen at high
      cooling rates?
AB  - Mouse spermatozoa in 18% raffinose and 3.8% Oxyrase in 0.25 x PBS exhibit high
      motilities when frozen to -70 degrees C at 20-130 degrees C/min and then rapidly
      warmed. However, survival is <10% when they are frozen at 260 or 530 degrees
      C/min, presumably because, at those high rates, intracellular water cannot leave
      rapidly enough to prevent extensive supercooling and this supercooling leads to
      nucleation and freezing in situ (intracellular ice formation [IIF]). The
      probability of IIF as a function of cooling rate can be computed by coupled
      differential equations that describe the extent of the loss of cell water during
      freezing and from knowledge of the temperature at which the supercooled
      protoplasm of the cell can nucleate. Calculation of the kinetics of dehydration
      requires values for the hydraulic conductivity (Lp) of the cell and for its
      activation energy (Ea). Using literature values for these parameters in mouse
      sperm, we calculated curves of water volume versus temperature for four cooling
      rates between 250 and 2000 degrees C/min. The intracellular nucleation
      temperature was inferred to be -20 degrees C or above based on the greatly
      reduced motilities of sperm that underwent rapid cooling to a minimum temperature
      of between -20 and -70 degrees C. Combining that information regarding nucleation
      temperature with the computed dehydration curves leads to the conclusion that
      intracellular freezing should occur only in cells that are cooled at 2000 degrees
      C/min and not in cells that are cooled at 250-1000 degrees C/min. The calculated
      rate of 2000 degrees C/min for IIF is approximately eightfold higher than the
      experimentally inferred value of 260 degrees C/min. Possible reasons for the
      discrepancy are discussed.

PMID- 11967215
TI  - Germ line stem cell competition in postnatal mouse testes.
AB  - Niche is believed to affect stem cell behavior. In self-renewing systems for
      which functional transplantation assays are available, it has long been assumed
      that stem cells are fixed in the niche and that ablative treatments to remove
      endogenous stem cells are required for successful donor engraftment. Our results
      demonstrate that enriched populations of donor stem cells can produce long
      lasting spermatogenic colonies in testes of immature and mature, nonablated mice,
      albeit at a lower frequency than in ablated mice. Colonization of nonablated
      recipient testes by neonate, pup, and cryptorchid adult donor spermatogonial stem
      cells demonstrates that competition for niche begins soon after birth and that
      endogenous stem cells influence the degree and pattern of donor cell
      colonization. Thus, a dynamic relationship between stem cell and niche exists in
      the testis, as has been suggested for hematopoiesis. Therefore, similar
      competitive properties of donor stem cells may be characteristic of all self
      renewing systems.

PMID- 11967216
TI  - Teleost ovarian carbonyl reductase-like 20beta-hydroxysteroid dehydrogenase:
      potential role in the production of maturation-inducing hormone during final
      oocyte maturation.
AB  - 17alpha,20beta-Dihydroxy-4-pregnen-3-one is the major oocyte maturation-inducing
      hormone of several teleost species. Gonadotropin-induced increase in ovarian
      20beta-hydroxysteroid dehydrogenase activity is essential for the synthesis of
      maturation-inducing hormone. Cloning and expression studies suggest that ayu
      (Plecoglossus altivelis) ovarian carbonyl reductase can function as 20beta
      hydroxysteroid dehydrogenase. The amino acid sequence deduced from the isolated
      cDNA had 276 amino acid residues and shared approximately 60% homology with
      mammalian and teleostean carbonyl reductases. The sequence data search showed
      that the ayu cDNA clone belongs to the short-chain dehydrogenase/reductase
      family. The clear lysate prepared from Escherichia coli harboring the cDNA
      catalyzed the production of maturation-inducing hormone. Its identification was
      confirmed by two-dimensional, thin-layer chromatography followed by
      recrystallization. Purification of the E. coli-expressed cDNA product revealed
      that it possessed both carbonyl reductase and steroid dehydrogenase activities,
      and 17alpha-hydroxyprogesterone, the endogenous immediate precursor of maturation
      inducing hormone, was one of the preferred substrates. Furthermore, Northern blot
      analysis denoted that the transcripts are present both in fully grown, immature
      ovarian follicles and at higher levels in mature ovarian follicles. These results
      demonstrate that the carbonyl reductase of ayu ovary is involved in the
      production of maturation-inducing hormone, and they provide evidence for a novel
      physiological role of this enzyme in the final maturation of oocytes. Based on
      its functional properties, the enzyme can be referred to as carbonyl reductase
      like 20beta-hydroxysteroid dehydrogenase.

PMID- 11967217
TI  - Transcriptional regulation of the cyclooxygenase-2 gene changes from protein
      kinase (PK) A- to PKC-dependence after luteinization of granulosa cells.
AB  - This study was designed to elucidate the molecular mechanism(s) mediating
      cyclooxygenase-2 (Cox-2) regulation during differentiation of the granulosa cell.
      The 5' flanking sequence of the Cox-2 gene was linked to a vector with a
      luciferase reporter gene, and this vector was transfected into freshly isolated
      bovine granulosa cells or granulosa cells after culture with or without forskolin
      to induce luteinization in vitro. The Cox-2 promoter was inducible by 8-bromo
      cAMP but not by phorbol esters in fresh granulosa cells, and maximal expression
      by cAMP was delayed until 48 h after treatment. In contrast, after luteinization
      of granulosa cells by 8-day treatment with forskolin, the Cox-2 promoter was
      immediately inducible by phorbol esters but not by cAMP. In granulosa cells
      cultured for 8 days without forskolin, the Cox-2 promoter continued to be
      inducible only by cAMP and not by phorbol esters. Unexpectedly, no delay was
      observed in the induction of Cox-2 by cAMP in granulosa cells that were cultured
      without forskolin, compared with an approximately 1 day delay in Cox-2 induction
      by cAMP in fresh granulosa cells. Myristoylated protein kinase (PK) A and PKC
      inhibitory peptides were utilized to further confirm the PKA- or PKC-dependence
      of Cox-2 induction. Time-course experiments showed that only 2 days of forskolin
      treatment could induce PKC-responsiveness of the Cox-2 promoter, although maximal
      responsiveness was not observed until 10 days of luteinization. Promoter activity
      was also analyzed in a series of deletion mutants as well as site-directed
      mutants of C/EBP, CRE, and E-box. A 282-base pair sequence in the Cox-2 5'
      flanking region maintained full inducibility by PKA in granulosa cells and by PKC
      in luteinized granulosa cells. The E-box element was found to be the critical
      regulatory element for Cox-2 induction by either PKA in granulosa cells or by PKC
      in luteinized granulosa cells. Electrophoretic mobility shift assays were
      performed on nuclear extracts from fresh or luteinized granulosa cells. Upstream
      stimulatory factor (USF)-1 and USF-2 bound to the E-box of the Cox-2 gene, and
      binding was similar for nuclear extracts from fresh, cultured, or luteinized
      granulosa cells. Thus, although luteinization changes transcriptional regulation
      of Cox-2 from PKA- to PKC-dependence, the crucial role of the E-box element in
      this transcriptional activation is conserved.

PMID- 11967218
TI  - Dynamic in vivo changes in tissue inhibitors of metalloproteinases 1 and 2, and
      matrix metalloproteinases 2 and 9, during prostaglandin F(2alpha)-induced
      luteolysis in sheep.
AB  - Prostaglandin F(2alpha) (PGF(2alpha)) typically initiates a cascade of events
      that leads to the functional and structural demise of the corpus luteum. A sheep
      model was used in which a 1-h, systemic infusion of PGF(2alpha) (20 microg/min)
      is given at midcycle. Such an infusion mimics the onset of spontaneous luteolysis
      by causing a transient decrease in peripheral plasma progesterone, which reaches
      a nadir ( approximately 60% of controls) at 8 h but returns to control levels by
      16-24 h. We investigated whether PGF(2alpha) also influenced the endogenous
      protein levels of tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2, and
      matrix metalloproteinases, MMP-2 and MMP-9, all of which have been implicated in
      remodeling of the extracellular matrix (ECM). Corpora lutea (Day 11) were
      collected at 0 h and at 1, 8, 16, and 24 h post-PGF(2alpha) infusion (n = 3 sheep
      at each time). Immunoblot analysis revealed an immediate and precipitous decline
      in TIMP-1 (30 kDa) and TIMP-2 (19 kDa) protein levels (60% and 90%, respectively;
      P < 0.05) at the 1-h time point and remained depressed at 8 h (P < 0.05). Gelatin
      zymography and other procedures identified three MMPs (85, 70, and 64 kDa), which
      were shown to be the latent form of MMP-9 and the active and latent forms of MMP
      2, respectively. In contrast to the rapid decrease in TIMP-1 and -2 levels, an
      increase in MMP-2 activity (165% of controls, P < 0.05) occurred at 8 h, which
      corresponded to the nadir in plasma progesterone. These early changes in TIMPs
      and MMPs indicate that alterations in the structure of the ECM by PGF(2alpha) may
      play a hitherto unsuspected role in the subsequent process of functional
      luteolysis.

PMID- 11967219
TI  - Sertoli cell vacuolization and abnormal germ cell adhesion in mice deficient in
      an inositol polyphosphate 5-phosphatase.
AB  - The dynamic nature of cellular interactions during differentiation of germ cells
      and their translocation from the basement membrane to the lumen of the
      seminiferous tubules requires the existence of complex and well-regulated
      cellular adhesion mechanisms in the testis. Successful migration of the
      developing germ cells is characterized by dynamic breakage and reformation of
      cadherin-containing adherens junctions between the germ cells and Sertoli cells,
      the polarized somatic cells of the testis that support and nourish the developing
      gametes. Here, we demonstrate the accumulation of abnormally swollen, actin
      coated, endosome-like structures that contain intact adherens junctions and stain
      positive for N-cadherin and beta-catenin in the Sertoli cell cytosol of mice
      deficient in Inpp5b, an inositol polyphosphate 5-phosphatase. Simultaneous to the
      formation of these abnormal structures, developing germ cells are prematurely
      released from the seminiferous epithelium and sloughed into the epididymis. Our
      results demonstrate a role for Inpp5b in the regulation of cell adhesion in the
      testis and in the formation of junctional complexes with neighboring cells, and
      they emphasize the important and essential role of phosphoinositides in
      spermatogenesis.

PMID- 11967220
TI  - Localization and expression of messenger RNAs for the peroxisome proliferator
      activated receptors in ovarian tissue from naturally cycling and pseudopregnant
      rats.
AB  - Structural and functional development of the corpus luteum (CL) involves tissue
      remodeling, angiogenesis, lipid metabolism, and steroid production. The
      peroxisome proliferator-activated receptors (PPARs) have been shown to play a
      role in these as well as in a multitude of other cellular processes. To examine
      the expression of mRNA corresponding to the PPAR family members (alpha, delta,
      and gamma) in luteal tissue, ovaries were collected from gonadotropin-treated,
      immature rats on Days 1, 4, 8, and 14 of pseudopregnancy and from adult, cycling
      animals on each day of the estrous cycle. Ovaries were processed for in situ
      hybridization or RNA isolation for analysis by RNase protection assay. The
      expression of PPARgamma mRNA was abundant in granulosa cells of developing
      follicles during both pseudopregnancy and the estrous cycle and was low to
      undetectable in CL from pseudopregnant rats. However, luteal tissue in cycling
      animals, especially CL remaining from previous cycles, had high levels of
      PPARgamma mRNA. The PPARalpha mRNA was localized mainly in the theca and stroma,
      and PPARdelta mRNA was expressed throughout the ovary. Levels of mRNA for
      PPARgamma decreased between Days 1 and 4 of pseudopregnancy, and PPARalpha mRNA
      levels were lower on the day of estrus compared to pro- and metestrus (P < 0.05).
      The PPARdelta mRNA levels remained steady throughout the estrous cycle and
      pseudopregnancy. These data illustrate a difference in the luteal expression of
      mRNA for PPARgamma between the adult, cycling rat and the immature, gonadotropin
      treated rat. This differential pattern of expression may be related to the
      difference in timing of the preovulatory prolactin surge, because the
      gonadotropin-primed animals would not experience a prolactin surge coincident
      with the LH surge, as occurs in adult, cycling animals. Additionally, the
      expression pattern of PPARdelta mRNA indicates that it may be involved in
      cellular functions involved with maintaining basal ovarian function, whereas
      PPARalpha may play a role in lipid metabolism in the theca and stroma.

PMID- 11967221
TI  - Androstenedione interferes in luteal regression by inhibiting apoptosis and
      stimulating progesterone production.
AB  - Androgens, in concert with lactogenic hormones, contribute to the maintenance of
      function of the corpus luteum (CL) in pregnant rats. Whereas some of the
      androgenic actions in the CL are clearly mediated by intracrine conversion to
      estrogen, pure androgenic effects are also implicated in the regulation of this
      transient endocrine gland. In this report, we have established, to our knowledge
      for the first time, the expression of androgen receptor (AR) mRNA and protein
      throughout gestation in the rat CL. We have found that the AR remains expressed
      in the CL of gestation on Day 4 postpartum and becomes expressed in the newly
      formed CL after postpartum ovulation. An AR immunoreactive protein was identified
      in the CL of pregnancy as well as in prostate and epididymis, which were used as
      positive controls. The luteal AR protein had mainly nuclear localization, yet
      some diffuse cytoplasmic staining was also observed. Moreover, we have
      established that androstenedione, the main circulating androgen in pregnant rats,
      significantly reduces the decline in luteal weight observed during postpartum
      structural regression. This effect was correlated with a decrease in the number
      of cells undergoing apoptosis and with enhanced levels of circulating
      progesterone. In addition, in vivo administration of androstenedione delayed the
      occurrence of DNA fragmentation in postpartum CL incubated in serum-free
      conditions. Finally, we have shown that the interference with apoptosis in vitro
      elicited by androstenedione is accompanied by an increased capacity of the CL to
      secrete progesterone. In summary, the results of this study have established that
      the rat CL expresses AR throughout pregnancy and after parturition, and they have
      defined a potential role for androstenedione in opposing postpartum luteal
      regression through inhibition of apoptosis and stimulation of progesterone
      production.

PMID- 11967222
TI  - Expression of leptin and its receptor in the murine ovary: possible role in the
      regulation of oocyte maturation.
AB  - Leptin is a product of the ob gene that is produced primarily by adipose tissue.
      Leptin and its receptors are found within the ovary, but it is unclear what
      function this hormone has in the ovary. Using immunohistochemistry, we determined
      that leptin is found in most cell types in the murine ovary, with the highest
      staining levels observed in the oocyte. Leptin receptor was also expressed in all
      of the main ovarian cell types, with the thecal cell layer exhibiting the highest
      staining levels. Leptin administration did not affect spontaneous or induced
      maturation of either isolated denuded oocytes or cumulus-oocyte complexes, but it
      did significantly increase the rate of meiotic resumption in preovulatory
      follicle-enclosed oocytes (P < 0.01). Measurements of cAMP within oocytes
      cultured with leptin showed that this enhanced ability to resume meiosis does not
      occur via activation of phosphodiesterase 3B and subsequent cAMP reduction. These
      results provide evidence that leptin affects oocyte maturation when the oocyte is
      cultured within its normal follicular environment. It is suggested that leptin
      may induce the production of another factor, possibly from thecal cells, that
      directly or indirectly acts on the oocyte to initiate germinal vesicle breakdown
      in this species.

PMID- 11967223
TI  - Central infusion of recombinant ovine leptin normalizes plasma insulin and
      stimulates a novel hypersecretion of luteinizing hormone after short-term fasting
      in mature beef cows.
AB  - The present studies tested the hypotheses that short-term fasting would reduce
      leptin gene expression and circulating concentrations of leptin and insulin in
      mature, ovariectomized, estradiol-implanted cows and that intracerebroventricular
      infusions of recombinant ovine leptin (oleptin) would attenuate reductions in
      insulin concentration and stimulate LH secretion. Ovariectomized cows were
      assigned to either control (normal fed; n = 6) or fasted (60 h of fasting; n = 7)
      groups and infused with 200 microg recombinant oleptin three times at hourly
      intervals on Day 2 (n = 6 per group). Fasting decreased plasma concentrations of
      insulin (P < 0.01) and leptin (P < 0.04) but, as expected, did not reduce plasma
      concentrations of glucose or any LH secretion variable. Central infusion of
      leptin on Day 2 increased (P < 0.01) plasma concentrations of leptin in both
      control and fasted groups. Concomitantly, leptin treatment increased plasma
      insulin (P < 0.01) and LH (P < 0.03) concentrations in fasted but not in control
      cows. Increases in overall mean and baseline concentrations of LH after leptin
      treatment were the result of an augmentation of the size of LH pulses. The
      effects of fasting on leptin gene expression and the potential diurnal effects on
      circulating leptin were examined in a group of cows (n = 12) not treated with
      leptin. Fasting for 60 h reduced (P < 0.001) leptin gene expression by 30%, and
      no diurnal effects on circulating leptin were observed. These results indicate
      that although short-term fasting does not reduce the frequency or amplitude of LH
      pulses or the concentration of LH in mature cows, this nutritional perturbation
      clearly sensitizes both the hypothalamic-pituitary axis and endocrine pancreas to
      exogenous leptin, which in these experiments resulted in heightened secretion of
      both LH and insulin.

PMID- 11967224
TI  - Impact of maternal undernutrition during the periconceptional period, fetal
      number, and fetal sex on the development of the hypothalamo-pituitary adrenal
      axis in sheep during late gestation.
AB  - Evidence from epidemiologic, clinical, and experimental studies has shown that a
      suboptimal intrauterine environment during early pregnancy can alter fetal growth
      and gestation length and is associated with an increased prevalence of adult
      hypertension and cardiovascular disease. It has been postulated that maternal
      nutrient restriction may act to reprogram the development of the pituitary
      adrenal axis, resulting in excess glucocorticoid exposure and adverse health
      outcomes in later life. It is unknown, however, whether maternal nutrient
      restriction during the periconceptional period alters the development of the
      fetal pituitary-adrenal axis or whether the effects of periconceptional
      undernutrition can be reversed by the provision of an adequate level of maternal
      nutrition throughout the remainder of pregnancy. We have investigated the effect
      of restricted periconceptional nutrition (70% of control feed allowance) from 60
      days before until 7 days after mating and the effect of restricted gestational
      nutrition from Day 8 to 147 of gestation on the development of the fetal
      hypothalamo-pituitary adrenal (HPA) axis in the sheep. In these studies, we have
      also investigated the effects of fetal number and sex on the pituitary-adrenal
      responses to periconceptional and gestational undernutrition. In ewes maintained
      on a control diet throughout the periconceptional and gestational periods, fetal
      plasma ACTH concentrations were higher and the prepartum surge in cortisol
      occurred earlier in singletons compared with twins. Plasma ACTH concentrations
      were also significantly higher in male compared with female singletons, and in
      twin fetuses, the prepartum surge in cortisol concentrations occurred earlier in
      males than in females. Periconceptional undernutrition resulted in higher fetal
      plasma concentrations of ACTH between 110 and 145 days of gestation and a
      significantly greater cortisol response to a bolus dose of corticotropin
      releasing hormone in twin, but not singleton, fetuses in late gestation. We have
      therefore demonstrated that fetal number and sex each has an impact on the timing
      of the prepartum activation of the HPA axis in the sheep. Restriction of the
      level of maternal nutrition before and in the first week of a twin pregnancy
      results in stimulation of the fetal pituitary-adrenal axis in late gestation, and
      this effect is not reversed by the provision of a maintenance control diet from
      the second week of pregnancy.

PMID- 11967225
TI  - Prolonged unloading of rat soleus muscle causes distinct adaptations of the gene
      profile.
AB  - Using commercially available microarray technology, we investigated a series of
      transcriptional adaptations caused by atrophy of rat m. soleus due to 35 days of
      hindlimb suspension. We detected 395 out of 1,200 tested transcripts, which
      reflected 1%-5% of totally expressed genes. From various cellular functional
      pathways, we detected multiple genes that spanned a 200-fold range of gene
      expression levels. Statistical analysis combining L1 regression with the sign
      test based on the conservative Bonferroni correction identified 105 genes that
      underwent transcriptional adaptations with atrophy. Generally, expressional
      changes were discrete (<50%) and pointed in the same direction for genes
      belonging to the same cellular functional units. In particular, a distinct
      expressional adaptation of genes involved in fiber transformation; that is,
      metabolism, protein turnover, and cell regulation were noted and matched to
      corresponding transcriptional changes in nutrient trafficking. Expressional
      changes of extracellular proteases, and of genes involved in nerve-muscle
      interaction and excitation-contraction coupling identify previously not
      recognized adaptations that occur in atrophic m. soleus. Considerations related
      to technical and statistical aspects of the array approach for profiling the
      skeletal muscle genome and the impact of observed novel adaptations of the m.
      soleus transcriptome are put into perspective of the physiological adaptations
      occurring with muscular atrophy.

PMID- 11967226
TI  - Reciprocal transmission of herpes simplex virus type 1 (HSV-1) between corneal
      epithelium and trigeminal neurites in an embryonic chick organ culture.
AB  - Reciprocal transmission between epithelia and sensory neurons of the peripheral
      nervous system is a crucial step in the life cycle of herpes simplex virus type 1
      (HSV-1) and related alphaherpesviruses. In searching for an easy-to-perform and
      generally applicable experimental approach that enables the direct analysis of
      virus transfer between primary epithelial cells and sensory neurites, we
      investigated the spread of HSV-1 in a dual-chamber organ model comprising chick
      embryonic corneal epithelia and trigeminal sensory neurons. Embryonic chick
      corneal and trigeminal tissues were found to be permissive for productive
      infection with HSV-1. Our data show that HSV-1 efficiently enters neurites re
      innervating the cornea and reaches the ganglion explant by retrograde axonal
      transport, with the first antigen-positive cells being detectable approximately
      12 h postinfection. After direct infection of trigeminal tissues, the virus is
      transported by anterograde axonal transport to the corneal epithelium, causing a
      visible cytopathic effect approximately 48 h postinfection. These results suggest
      that the organ model presented in this study holds particular promise for the
      direct observation and molecular analysis of herpes simplex virus spread between
      primary epithelia and sensory neurons and that it may be an attractive
      alternative to current experimental approaches based on laboratory animals or
      human fetal tissues.

PMID- 11967227
TI  - Membrane lipids, EGF receptors, and intracellular signals colocalize and are
      polarized in epithelial cells moving directionally in a physiological electric
      field.
AB  - Directed cell migration is essential for tissue formation, inflammation, and
      wound healing. Chemotaxis plays a major role in these situations and is
      underpinned by asymmetric intracellular signaling. Endogenous electric fields
      (EFs) are common where cell movement occurs, such as in wound healing, and cells
      respond to electric field gradients by reorienting and migrating directionally
      (galvanotaxis/electrotaxis). We show that a physiological EF redistributed both
      EGF (epidermal growth factor) receptors and detergent-insoluble membrane lipids
      asymmetrically, leading to cathodal polarization and enhanced activation of the
      MAP kinase, ERK1/2. This induced leading-edge actin polymerization in
      directionally migrating mammalian epithelial cells. Inhibiting the EGF receptor
      MAP kinase signaling pathway significantly decreased leading edge actin asymmetry
      and directional migration. We propose a model in which EF-polarized membrane
      lipid domains and EGF receptors cause asymmetric signaling through MAP kinase,
      which drives directional cell migration. A comparison is made with the mechanisms
      underpinning chemotaxis.

PMID- 11967228
TI  - Reduction of amyloid load and cerebral damage in a transgenic mouse model of
      Alzheimer's disease by treatment with a beta-sheet breaker peptide.
AB  - Genetic, neuropathological, and biochemical studies have provided strong evidence
      for a central role of amyloid in the pathogenesis of Alzheimer's disease (AD). We
      have proposed previously that peptides designed as beta-sheet breakers may be
      useful in preventing the formation of amyloid plaques. In this study, we describe
      a modified beta-sheet breaker peptide with improved pharmacological properties, a
      high rate of penetration across the blood-brain barrier, and the ability to
      induce a dramatic reduction in amyloid deposition in two different transgenic AD
      models. In addition, we report for the first time a significant increase in
      neuronal survival and a decrease in brain inflammation associated with the
      reduction of amyloid plaques. These results demonstrate that the process of
      amyloid deposition is one of the causes of neurodegeneration in AD. Moreover, our
      findings indicate that beta-sheet breaker peptides provide a valuable tool for
      evaluating further the importance of amyloid in the etiology of AD and suggest
      that these peptides or some of their derivatives might be good candidates for AD
      treatment.

PMID- 11967229
TI  - ClC-3B, a novel ClC-3 splicing variant that interacts with EBP50 and facilitates
      expression of CFTR-regulated ORCC.
AB  - We have cloned ClC-3B, a novel alternative splicing variant of ClC-3 (ClC-3A)
      that is expressed predominantly in epithelial cells. ClC-3B has a different,
      slightly longer C-terminal end than ClC-3A and contains a consensus motif for
      binding to the second PDZ (PSD95/Dlg/ZO-1) domain of the epithelium-specific
      scaffolding protein EBP50. Both in vitro and in vivo binding assays demonstrate
      interaction between ClC-3B and EBP50. C127 mouse mammary epithelial cells
      transfected with ClC-3B alone showed diffuse immunoreactivity for ClC-3B in the
      cytoplasmic region. In contrast, when EBP50 was cotransfected with ClC-3B, strong
      immunoreactivity for ClC-3B appeared at the leading edges of membrane ruffles.
      Patch-clamp experiments revealed that cotransfection of ClC-3B and EBP50 resulted
      in a remarkable increase in outwardly rectifying Cl- channel (ORCC) activities at
      the leading edges of membrane ruffles in C127 cells. The electrophysiological
      properties of the ClC-3B-induced ORCCs are similar to those of ORCCs described in
      native epithelial cells. When cystic fibrosis transmembrane conductance regulator
      (CFTR) was cotransfected with ClC-3B and EBP50, ClC-3B-dependent ORCCs were
      activated via the protein kinase A-dependent pathway. These findings indicate
      that ClC-3B is itself a CFTR-regulated ORCC molecule or its activator.

PMID- 11967230
TI  - Microfilament-dependent movement of the beta3 integrin subunit within focal
      contacts of endothelial cells.
AB  - To gain insight into the dynamic properties of focal contacts, we induced
      expression of green fluorescent protein-tagged beta3 integrin (GFP-beta3) and
      actinin-1 (GFP-actinin-1) in endothelial cells. Both tagged proteins localize
      with alpha(v)beta3 integrin in focal contacts distributed towards the periphery
      of transfected cells. Labeled focal contacts migrate at about 0.1 mm/min in
      stationary live endothelial cells. We compared beta3 integrin and actinin-1
      dynamics in focal contacts by using fluorescence recovery after photobleaching.
      Recovery of signal in bleached focal contacts that have incorporated actinin-1 is
      rapid and occurs within less than 4 min. This recovery is energy-dependent. In
      contrast, recovery of bleached focal contacts that contain GFP-beta3 integrin
      takes longer than 30 min. Yet, when a narrow stripe of fluorescence is bleached
      across a beta3 integrin-labeled focal contact, recovery is complete within 16
      min. The latter recovery is energy-dependent and is blocked not only by actin
      filament disrupting drugs but also by a myosin light chain kinase inhibitor.
      Thus, integrins are not immobile when incorporated into focal contacts, as some
      have suggested. We propose that integrins are mobile within the confines of focal
      contacts and that this mobility is supported by an actin-associated molecular
      motor.

PMID- 11967231
TI  - Generation of therapeutic antibody responses against IgE through vaccination.
AB  - IgE is the central mediator in atopic allergies such as hay fever, eczema, and
      asthma; therefore, it is a prime target in the development of allergen
      independent preventive treatments. We describe an active immunization strategy
      that has the potential to reduce IgE to a clinically significant extent. The
      active vaccine component is a chimeric IgE molecule, Cepsilon2-Cepsilon3
      Cepsilon4. The receptor-binding target domain, Cepsilon3, is derived from the
      recipient species, whereas the flanking domains, Cepsilon2 and Cepsilon4, are
      derived from an evolutionarily distant mammal. The flanking domains have dual
      functions, acting both as structural support for the Cepsilon3 domain and to
      break T cell tolerance by providing foreign T cell epitopes. The efficacy of the
      vaccine was studied in an ovalbumin-sensitized rat model. Vaccination resulted in
      antibody responses against IgE in all rats and in a substantial reduction in
      serum IgE levels in three out of four strains. The skin reactivity upon allergen
      challenge was significantly reduced in vaccinated animals. The vaccine appears to
      be safe to use as an antigen. No cross-linking activity was observed in sera of
      vaccinated animals, and the response to vaccination was reversible with time. Our
      results suggest that active immunization against IgE has the potential to become
      a therapeutic method for humans.

PMID- 11967232
TI  - Biological and genetic properties of the p53 null preneoplastic mammary
      epithelium.
AB  - The absence of the tumor suppressor gene p53 confers an increased tumorigenic
      risk for mammary epithelial cells. In this report, we describe the biological and
      genetic properties of the p53 null preneoplastic mouse mammary epithelium in a
      p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted
      serially into the cleared mammary fat pads of p53 wild-type BALB/c female to
      develop stable outgrowth lines. The outgrowth lines were transplanted for 10
      generations. The outgrowths were ductal in morphology and progressed through
      ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The
      preneoplastic outgrowth lines were immortal and exhibited activated telomerase
      activity. They are estrogen and progesterone receptor-positive, and aneuploid,
      and had various levels of tumorigenic potential. The biological and genetic
      properties of these lines are distinct from those found in most hyperplastic
      alveolar outgrowth lines, the form of mammary preneoplasia occurring in most
      traditional models of murine mammary tumorigenesis. These results indicate that
      the preneoplastic cell populations found in this genetically engineered model are
      similar in biological properties to a subset of precurser lesions found in human
      breast cancer and provide a unique model to identify secondary events critical
      for tumorigenicity and invasiveness.

PMID- 11967233
TI  - Evidence of connective tissue involvement in acupuncture.
AB  - Acupuncture needle manipulation gives rise to "needle grasp," a biomechanical
      phenomenon characterized by an increase in the force necessary to pull the needle
      out of the tissue (pullout force). This study investigates the hypothesis that
      winding of connective tissue, rather than muscle contraction, is the mechanism
      responsible for needle grasp. We performed 1) measurements of pullout force in
      humans with and without needle penetration of muscle; 2) measurements of pullout
      force in anesthetized rats, with and without needle rotation, followed by
      measurements of connective tissue volume surrounding the needle; 3) imaging of
      rat abdominal wall explants, with and without needle rotation, using ultrasound
      scanning acoustic microscopy. We found 1) no evidence that increased penetration
      of muscle results in greater pullout force than increased penetration of
      subcutaneous tissue; 2) that both pullout force and subcutaneous tissue volume
      were increased by needle rotation; 3) that increased periodic architectural order
      was present in subcutaneous tissue with rotation, compared with no rotation.
      These data support connective tissue winding as the mechanism responsible for the
      increase in pullout force induced by needle rotation. Winding may allow needle
      movements to deliver a mechanical signal into the tissue and may be key to
      acupuncture's therapeutic mechanism.

PMID- 11967234
TI  - Preferential transformation of human neuronal cells by human adenoviruses and the
      origin of HEK 293 cells.
AB  - The 293 cell line was derived by transformation of primary cultures of human
      embryonic kidney (HEK) cells with sheared adenovirus (Ad)5 DNA. A combination of
      immunostaining, immunoblot, and microarray analysis showed that 293 cells express
      the neurofilament (NF) subunits NF-L, NF-M, NF-H, and a-internexin as well as
      many other proteins typically found in neurons. Three other independently derived
      HEK lines, two transformed by Ad5 and one by Ad12, also expressed NFs, as did one
      human embryonic retinal cell line transformed with Ad5. Two rodent kidney lines
      transformed with Ad12 were also found to express NF proteins, although several
      rodent kidney cell lines transformed by Ad5 DNA and three HEK cell lines
      transformed by the SV40 early region did not express NFs. These results suggest
      that human Ads preferentially transform human neuronal lineage cells. We also
      demonstrate that the widely used HEK293 cells have an unexpected relationship to
      neurons, a finding that may require reinterpretation of many previous studies in
      which it was assumed that HEK293 cells resembled more typical kidney epithelial
      cells.

PMID- 11967236
TI  - In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage.
AB  - The klotho gene, originally identified by insertional mutagenesis in mice,
      suppresses the expression of multiple aging-associated phenotypes. This gene is
      predominantly expressed in the kidney. Recent studies have shown that expression
      of renal klotho gene is regulated in animal models of metabolic diseases and in
      humans with chronic renal failure. However, little is known about the mechanisms
      and the physiological relevance of the regulation of the expression of the klotho
      gene in the kidney in some diseased conditions. In the present study, we first
      investigated the role of angiotensin II in the regulation of renal klotho gene
      expression. Long-term infusion of angiotensin II downregulated renal klotho gene
      expression at both the mRNA and protein levels. This angiotensin II-induced renal
      klotho downregulation was an angiotensin type 1 receptor-dependent but pressor
      independent event. Adenovirus harboring mouse klotho gene (ad-klotho, 3.3x10(10)
      plaque forming units) was also intravenously administered immediately before
      starting angiotensin II infusion in some rats. This resulted in a robust
      induction of Klotho protein in the liver at day 4, which was still detectable 14
      days after the gene transfer. Ad-klotho gene transfer, but not ad-lacZ gene
      transfer, caused an improvement of creatinine clearance, decrease in urinary
      protein excretion, and amelioration of histologically demonstrated
      tubulointerstitial damage induced by angiotensin II administration. Our data
      suggest that downregulation of the renal klotho gene may have an aggravative role
      in the development of renal damage induced by angiotensin II, and that induction
      of the klotho gene may have therapeutic possibilities in treating angiotensin II
      induced end organ damage.

PMID- 11967237
TI  - Impaired stress-induced pressure natriuresis is related to left ventricle
      structure in blacks.
AB  - The mechanisms through which stress may contribute to the racial difference in
      the prevalence of essential hypertension and associated target organ damage
      remain unclear. This study examined differences in stress-induced pressure
      natriuresis in 69 black and 52 white normotensives age 14 to 27 years, all with a
      positive family history of hypertension. Urine samples for sodium excretion were
      collected before and after a series of tasks (video game challenge, forehead cold
      stimulation). The average blood pressure across the 2 tasks and the average
      increase in blood pressure to the 2 tasks were calculated. Blacks had higher mean
      systolic (131+/-12 versus 126+/-12 mm Hg, P<0.02) and diastolic (77+/-8 versus
      72+/-9 mm Hg, P<0.001) blood pressure and a greater average change in systolic
      blood pressure (15+/-9 versus 11+/-7 mm Hg, P<0.04). This was associated with a
      smaller change in sodium excretion (2+/-6 versus 7+/-10 mEq/h, P<0.002). The
      change in sodium excretion was related to the change in systolic (r=0.31, P<0.03)
      and diastolic (r=0.27, P<0.05) blood pressure in whites but not in blacks.
      Relative wall thickness was greater in blacks (0.31+/-0.04 versus 0.29+/-0.03,
      P<0.002). In conclusion, impaired stress-induced pressure natriuresis in blacks
      may contribute to racial differences in essential hypertension and its sequelae.

PMID- 11967238
TI  - Epithelial COX-2 expression is not regulated by nitric oxide in rodent renal
      cortex.
AB  - In the adult rodent kidney cortex, cyclooxygenase-2 (COX-2), NO synthase (NOS1),
      and renin synthesis change in parallel on alterations in distal tubular NaCl
      concentration, and their products in part may mutually determine synthesis and
      activity of these enzymes. Epithelial NO synthesis has been postulated to exert a
      stimulatory role on COX-2 expression. Changes in COX-2 and NOS1 may be assessed
      histochemically by determining changes in the number of positive cells. In rat,
      macula densa and adjacent cells may co-express COX-2 and NOS1, whereas cell
      groups of the upstream thick ascending limb (cTAL) express COX-2 alone. We have
      tested whether the stimulation of COX-2 expression by short- and long-term
      unilateral renal artery stenosis, low salt, and furosemide treatment depends on
      co-expression of NOS1. These conditions produced significant respective increases
      (40% to 351%, P<0.05) in the number of COX-2 immunoreactive cells, regardless of
      whether NOS1 was present or not, suggesting that co-expression of NOS1 is not
      necessary to produce these changes. Under high-salt conditions, analogous though
      inverse changes were recorded (-62% to -73%, P<0.05). In mice with genetic
      deletion of NOS1, low- and high-salt diets caused similar changes of COX-2
      immunoreactivity (106% and -52%, P<0.05) than those seen in wild-type mice (43%
      and -78%, P<0.05). We conclude that alterations of distal tubular NaCl
      concentration and presumably NaCl transport induce changes in epithelial COX-2
      expression that does not depend on presence of co-expressed NOS1. It therefore
      seems unlikely that NO is part of a signal transduction chain between tubular
      chloride sensing and the modulating effects of prostaglandins in tubulo-vascular
      information transfer.

PMID- 11967239
TI  - Catecholamines block 2-hydroxyestradiol-induced antimitogenesis in mesangial
      cells.
AB  - Methylation of 2-hydroxyestradiol to 2-methoxyestradiol by catechol-O-methyl
      transferase (COMT) mediates the antimitogenic effects of 2-hydroxyestradiol on
      vascular smooth muscle cells. Moreover, 2-hydroxyestradiol inhibits growth of
      glomerular mesangial cells (GMCs). Because catecholamines are substrates for
      COMT, which is expressed in GMCs, we hypothesize that catecholamines may abrogate
      the antimitogenic effects of 2-hydroxyestradiol on GMCs by competing for COMT and
      inhibiting 2-methoxyestradiol formation. To test this hypothesis, we investigated
      the antimitogenic effects of 2-hydroxyestradiol on rat GMCs in the presence and
      absence of catecholamines. The capability of GMCs to methylate 2-hydroxyestradiol
      in the presence and absence of catecholamines was also evaluated. GMCs
      metabolized 2-hydoxyestradiol in a concentration-dependent manner with a V(max)
      of 12.03+/-0.32 pmol/10(6) cells/min and an apparent K(m) of 0.23+/-0.04
      micromol/L. Norepinephrine (10 micromol/L) and epinephrine (10 micromol/L)
      significantly inhibited methylation of 0.25 micromol/L 2-hydroxyestradiol.
      Norepinephrine concentration-dependently abrogated the ability of 2
      hydroxyestradiol to inhibit 3H-thymidine incorporation (index of DNA synthesis).
      In the presence of 5, 10, and 40 micromol/L norepinephrine, the inhibitory effect
      of 0.1 micromol/L 2-hydroxyestradiol on 3H-thymidine incorporation was reduced
      from 51+/-0.7% to 46+/-0.4%, 39+/-0.3%, and 25+/-0.7%, respectively. Similar to
      DNA synthesis, the inhibitory effects of 2-hydroxyestradiol on cell number and 3H
      proline incorporation (index of collagen synthesis) on GMCs were abrogated by
      catecholamines. Our findings provide evidence that methylation of 2
      hydroxyestradiol inhibits GMC proliferation and extracellular matrix synthesis
      and may in part protect against renal proliferative diseases. Moreover,
      catecholamines may abrogate the renoprotective effects of 2-hydroxyestradiol in
      the glomeruli by inhibiting COMT and 2-methoxyestradiol formation.

PMID- 11967240
TI  - Serine protease activity in m-1 cortical collecting duct cells.
AB  - An apical serine protease, channel-activating protease 1 (CAP1), augments sodium
      transport in A6 cells. Prostasin, a novel serine protease originally purified
      from seminal fluid, has been proposed to be the mammalian ortholog of CAP1. We
      have recently found functional evidence for a similar protease activity in the M
      1 cortical collecting duct cell line. The purposes of the present studies were to
      determine whether prostasin (or CAP1) is present in collecting duct cells by use
      of mouse M-1 cells, to sequence mouse prostasin, and to further characterize the
      identity of the serine protease activity and additional functional features in M
      1 cells. Using mouse expressed sequence tag sequences that are highly homologous
      to the published human prostasin sequence as templates, reverse transcription
      polymerase chain reaction and RACE (rapid amplification of cDNA ends) were used
      to sequence mouse prostasin mRNA, which shows 99% identical to published mouse
      CAP1 sequence. A single 1800-bp transcript was found by Northern analysis, and
      this was not altered by aldosterone. Equivalent short-circuit current (I(eq)),
      which represents sodium transport in these cells, dropped to 59+/-3% of control
      value within 1 hour of incubation with aprotinin, a serine protease inhibitor.
      Trypsin increased the I(eq) in aprotinin-treated cells to the value of the
      control group within 5 minutes. Application of aprotinin not only inhibited
      amiloride sensitive I(eq) but also reduced transepithelial resistance (R(te)) to
      43+/-2%, an effect not expected with simple inhibition of sodium channels.
      Trypsin partially reversed the effect of aprotinin on R(te). Another serine
      protease inhibitor, soybean trypsin inhibitor (STI), decreased I(eq) in M-1
      cells. STI inhibited I(eq) gradually over 6 hours, and the inhibition of I(eq) by
      2 inhibitors was additive. STI decreased transepithelial resistance much less
      than did aprotinin. Neither aldosterone nor dexamethasone significantly augmented
      protease activity or prostasin mRNA levels, and in fact, dexamethasone decreased
      prostasin mRNA expression. In conclusion, although prostasin is present in M-1
      cells and probably augments sodium transport in these cells, serine proteases
      probably have other effects (eg, resistance) in the collecting duct in addition
      to effects on sodium channels. Steroids do not alter these effects in M-1 cells.
      Additional proteases are likely also present in mouse collecting duct cells.

PMID- 11967241
TI  - Altered regulation of matrix metalloproteinase-2 in aortic remodeling during
      aging.
AB  - To elucidate potential mechanisms of enhanced type 2 matrix metalloprotease
      levels and activity within the thickened aged rat aorta, the present study
      measured its mRNA and protein levels and those of its membrane bound activator,
      MT1-MMP, its endogenous tissue inhibitor, TIMP-2, tissue type, and urokinase
      plasminogen activators and their receptors, and an inhibitor of plasminogen
      activation in aortae from Fisher 344X Brown Norway rats, 2 to 30 months of age.
      Semiquantitative immunohistochemistry, in situ hybridization, and in situ
      zymography of aortae detected a marked age-associated increase in gelatinolytic
      activity of type 2 metalloprotease within the thickened intima, internal elastic
      lamina, and elastic fibers in the inner part of the thickened tunica media,
      whereas the intimal tissue inhibitor of metalloprotease-2 mRNA and protein levels
      were not age related. Both activators of plasminogen and their receptors
      increased approximately 2-fold within the intima between 2 to 30 months. Similar,
      but not identical, age-associated changes in factors that regulate protease
      activity within the aortic media were also observed. We conclude that discordant
      regulation of factors that determine the activation status of type 2 matrix
      metalloprotease, coupled with an increase in the expression of its zymogen, occur
      with aging, which lead to an increase in the amount of activated protease. These
      factors are candidate mechanisms for age-associated vascular remodeling, a potent
      risk factor for vascular diseases with advancing age.

PMID- 11967242
TI  - Methoxyestradiols mediate estradiol-induced antimitogenesis in human aortic SMCs.
AB  - Estrogen receptors (ERs) are considered to mediate the ability of 17beta
      estradiol (estradiol) to reduce injury-induced proliferation of vascular smooth
      muscle cells (VSMCs), leading to vascular lesions. However, the finding that
      estradiol attenuates formation of vascular lesions in response to vascular injury
      in knockout mice that lack either ER-alpha or ER-beta challenges this concept.
      Our hypothesis is that the local metabolism of estradiol to methoxyestradiols,
      metabolites of estradiol with little affinity for ERs, mediates the ER
      independent antimitogenic effects of estradiol on VSMCs. In human VSMCs, 2
      methoxyestradiol and 2-hydroxyestradiol were more potent than was estradiol in
      inhibiting DNA synthesis (3[H]-thymidine incorporation), collagen synthesis (3[H]
      proline incorporation), cell proliferation (cell number), and cell migration
      (movement of cells across a polycarbonate membrane). The inhibitory effects of
      estradiol on VSMCs were enhanced by cytochrome-P450 (CYP450) inducers 3
      methylcholanthrene and phenobarbital. Moreover, the inhibitory effects of
      estradiol were blocked in the presence of the CYP450 inhibitor 1
      aminobenzotriazole and the catechol-O-methyltransferase inhibitors quercetin and
      OR486. Both OR486 and quercetin blocked the conversion of 2-hydroxyestradiol to 2
      methoxyestradiol; moreover, they blocked the antimitogenic effects of 2
      hydroxyestradiol but not of 2-methoxyestradiol. The ER antagonist ICI182780
      blocked the inhibitor effects of estradiol on VSMCs, but only at concentrations
      (>50 micromol/L) that also inhibit the metabolism of estradiol to
      hydroxyestradiols (precursors of methoxyestradiols). In conclusion, the
      inhibitory effects of locally applied estradiol on human VSMCs are mediated via a
      novel ER-independent mechanism involving estradiol metabolism. These findings
      imply that vascular estradiol metabolism may be an important determinant of the
      cardiovascular protective effects of estradiol and that nonfeminizing estradiol
      metabolites may confer cardiovascular protection regardless of gender.

PMID- 11967243
TI  - Neuronal NO mediates cerebral vasodilator responses to K+ in hypertensive rats.
AB  - Potassium ion (K+) normally causes cerebral vasodilatation by activating inwardly
      rectifying K+ (K(IR)) channels. We tested whether chronic hypertension affects
      the magnitude and/or mechanism of K+-induced cerebral vasodilatation in vivo.
      Basilar artery responses were examined in anesthetized Wistar-Kyoto (WKY; mean
      arterial pressure, 114+/-4 mm Hg) and spontaneously hypertensive (SHR; 176+/-3 mm
      Hg) rats. In WKY, elevating cerebrospinal fluid K+ concentration from 3 mmol/L to
      5 and 10 mmol/L caused vasodilatation (percent maximum, 12+/-1 and 48+/-7,
      respectively). The response to 5 mmol/L K+ was greater in SHR (percent maximum,
      17+/-2 [P<0.05 versus WKY] and 49+/-4). The K(IR) channel inhibitor, barium ion
      (Ba2+, 100 micromol/L) selectively inhibited dilator responses to 5 and 10 mmol/L
      K+ by approximately 75% in WKY. In SHR, Ba2+ had no effect on the response to 5
      mmol/L K+, and only partially inhibited (by approximately 40%) the response to 10
      mmol/L K+. The nonselective NO synthase (NOS) inhibitor N(omega)-nitro-L-arginine
      methyl ester, the neuronal NOS (nNOS) inhibitor 1-(2-trifluromethyl
      phenyl)imidazole, and the N-type calcium channel inhibitor omega-conotoxin GVIA,
      were all without effect in WKY, but markedly inhibited the response to 5 mmol/L
      K+ in SHR. When applied together with Ba2+, each of these inhibitors also
      profoundly reduced responses to 10 mmol/L K+ in SHR. Immunostaining of basilar
      arteries revealed that the perivascular nNOS-containing nerve plexus was denser
      in SHR. Thus, K+ dilates the normotensive basilar artery predominantly via K(IR)
      channel activation. During chronic hypertension, small physiological elevations
      in K+ dilate the basilar artery by an nNOS-dependent mechanism that appears to be
      upregulated in a compensatory manner.

PMID- 11967244
TI  - Sympathetic response to ventricular extrasystolic beats in hypertension and heart
      failure.
AB  - Provoked premature ventricular contractions (PVCs) evoke, in concomitance with an
      early and late blood pressure fall and overshoot, an early sympathoexcitation and
      a later period of sympathoinhibition, respectively. The present study was
      designed to examine whether in healthy subjects this is the case for spontaneous
      PVCs. Because of their pathophysiological relevance for arrhythmogenesis, it was
      also designed to determine whether the sympathetic responses are different from
      those seen in essential hypertension and congestive heart failure. In 14
      untreated mild essential hypertensives (EH; age, 53.8+/-2.6 years; mean+/-SEM),
      20 untreated congestive heart failure patients (CHF; age, 56.7+/-2.5 years; New
      York Heart Association class, II or III), and 16 age-matched healthy subjects
      (control) in Lown class <II, we evaluated the blood pressure (Finapres), heart
      rate (ECG), and muscle sympathetic nerve traffic (MSNA; by microneurography)
      responses to isolated monofocal PVCs. MSNA, quantified as bursts/100 heart beats,
      was significantly increased in EH (57.8+/-3.8, P<0.05) and CHF patients (77.7+/
      4.0, P<0.01) compared with controls (44.6+/-4.4). In controls, the PVC-induced
      blood pressure fall and overshoot were accompanied by a sympathoexcitation
      (144.2+/-14%), followed by a period of sympathoinhibition (average duration,
      12043+/-985 ms). The responses were similar in EH but not in CHF, in whom the
      magnitude of the sympathoexcitation and particularly the duration of the
      subsequent sympathoinhibition were strikingly reduced (average reduction, -46.1
      and -72.8%, respectively). The most important factor accounting for this
      reduction appeared to be an altered baroreflex response to the PVC-induced BP
      changes. These data demonstrate that the MSNA responses to spontaneous PVCs are
      similar in controls and EH but markedly impaired in CHF, presumably because of
      the baroreflex alteration. This may represent an important factor for the genesis
      of the life-threatening ventricular arrhythmias that characterize CHF.

PMID- 11967245
TI  - Effects of chronic calcium channel blockade on sympathetic nerve activity in
      hypertension.
AB  - The sympathetic nervous system (SNS) is an important regulator of the
      circulation. Its activity is increased in hypertension and heart failure and
      adversely affects prognosis. Although certain drugs inhibit SNS, dihydropyridine
      calcium antagonists may stimulate the system. Phenylalkylamine calcium
      antagonists such as verapamil have a different pharmacological profile. We
      therefore tested the hypothesis of whether amlodipine, nifedipine, or verapamil
      differs in the effects on muscle sympathetic nerve activity (MSA). Forty-three
      patients (31 men, 12 women) with mild to moderate hypertension were randomly
      assigned to 1 drug for 8 weeks. Blood pressure, heart rate, and MSA (by
      microneurography) were measured at baseline and after 8 weeks of treatment. All
      calcium antagonists led to a similar decrease in blood pressure of 5.0+/-1.5 to
      6.4+/-1.4 mm Hg at 8 weeks (P<0.001 versus baseline). There were no significant
      differences in MSA between groups. With amlodipine, MSA averaged 49+/-3
      bursts/min (3 versus baseline); with nifedipine, 48+/-3 bursts/min (2 versus
      baseline); and with verapamil, 49+/-2 bursts/min (all, P=NS). With verapamil,
      norepinephrine decreased by 4% but tended to increase by about one third with
      amlodipine or nifedipine (P=NS). Thus, in hypertension slow release forms of
      verapamil, nifedipine, and amlodipine exert comparable antihypertensive effects
      and do not change MSA, although there was a trend toward decreased MSA and plasma
      norepinephrine with verapamil.

PMID- 11967246
TI  - The impact of JNC-VI guidelines on treatment recommendations in the US
      population.
AB  - Using epidemiological and clinical trial evidence, the sixth report of the Joint
      National Committee on Prevention, Detection, and Treatment of High Blood Pressure
      (JNC-VI) updated previous guidelines to suggest that in addition to blood
      pressure, decisions on initial treatment should emphasize absolute cardiovascular
      disease risk. We estimated the impact of using cardiovascular disease risk on
      treatment recommendations for the US population using data from 16 527
      participants in the Third National Health and Nutrition Examination Survey. In
      the US population > or =20 years of age, 36% (62 million) had high-normal blood
      pressure or greater (systolic/diastolic blood pressure > or =130 mm Hg/> or =85
      mm Hg) or were taking antihypertensive medication. Of this population, 5.1% (3.2
      million) were stratified into risk group A (no cardiovascular disease risk
      factors or prevalent cardiovascular disease), 66.3% (41.4 million) into risk
      group B (> or =1 major risk factor), and 28.6% (17.9 million) into risk group C
      (diabetes mellitus, clinical cardiovascular disease, target organ damage). Also,
      26% of this group (16.2 million) had high-normal blood pressure and were in risk
      groups A or B, a context in which vigorous lifestyle modification is recommended
      in the JNC-VI guidelines. Additionally, 11% (7.0 million) had high-normal blood
      pressure (systolic/diastolic, 130 to 139 mm Hg/85 to 89 mm Hg, respectively) or
      stage-1 hypertension (140 to 159 mm Hg/90 to 99 mm Hg), and at least 1 factor,
      placing them in risk group C, but they were not currently on antihypertensive
      medication. JNC-VI, but not previous JNC guidelines, specifically recommends drug
      therapy as initial treatment for these patients. We conclude that JNC-VI refines
      cardiovascular risk and enfranchises more Americans to undertake more aggressive
      risk reduction maneuvers.

PMID- 11967247
TI  - Ambulatory blood pressure and left ventricular mass index in hypertensive
      children.
AB  - To determine whether ambulatory blood pressure is more predictive of left
      ventricular hypertrophy than is casual blood pressure in hypertensive children,
      echocardiography and ambulatory blood pressure data from 37 untreated
      hypertensive children were analyzed. Left ventricular mass was calculated using
      the Devereux equation, left ventricular mass index was calculated as left
      ventricular mass (in grams)/height(2.7) (in meters), and left ventricular
      hypertrophy was defined as left ventricular mass index >51 g/m(2.7). Average
      blood pressure, blood pressure load, and blood pressure index (average blood
      pressure divided by pediatric ambulatory blood pressure 95th percentile) were
      calculated. Left ventricular mass index was strongly correlated with 24-hour
      systolic blood pressure index (r=0.43, P=0.008) and was also correlated with 24
      hour systolic blood pressure (r=0.34, P=0.037), 24-hour systolic blood pressure
      load (r=0.38, P=0.020), wake systolic blood pressure load (r=0.37, P=0.025),
      sleep systolic blood pressure (r=0.33, P=0.048), and sleep systolic blood
      pressure load (r=0.38, P=0.021). Left ventricular mass index did not correlate
      with age, weight, clinic blood pressure, or ambulatory diastolic blood pressure.
      The overall prevalence of left ventricular hypertrophy was 27%. The prevalence of
      left ventricular hypertrophy was 47% (8 of 17) in patients with both systolic
      blood pressure load >50% and 24-hour systolic blood pressure index >1.0, compared
      with 10% (2 of 20) in patients without both criteria (P=0.015). These data
      suggest ambulatory blood pressure monitoring may be useful for the clinical
      assessment of hypertensive children by identifying those at high risk for the
      presence of end organ injury.

PMID- 11967248
TI  - Ambulatory blood pressure in 12-year-old children born small for gestational age.
AB  - An association between low birth weight and subsequent elevated blood pressure
      has been demonstrated in a large number of studies, but the number of subjects
      born small for gestational age in these studies has been negligible. The inverse
      relationship between birth weight and blood pressure in children has been
      evaluated previously with an ambulatory blood pressure device, but only in
      children with normal birth weights. In this prospective case-control study from
      birth to the age of 12, we evaluated the ambulatory blood pressures in 50
      children born at term but small for gestational age and in 50 full-term children
      born appropriate for gestational age. Children born small for gestational age had
      similar mean+/-SD systolic (117.5+/-8.5 mm Hg versus 115.3+/-7.4 mm Hg, P=0.221),
      and diastolic (69.2+/-5.3 mm Hg versus 67.3+/-4.4 mm Hg, P=0.075) 24-hour
      ambulatory blood pressure compared with the values of the children born
      appropriate for gestational age. However, 24-hour systolic blood pressure in the
      small-for-gestational-age children was higher (3.90 mm Hg; 95% confidence
      interval, 0.65 to 7.15) after adjusting for current body mass index. The
      difference in current body mass index was the only determinant for the difference
      in systolic blood pressure between the groups. Birth weight had no direct
      association with the blood pressure values. Impaired fetal growth may have a
      relationship with higher later blood pressure, but in 12-year-old children, blood
      pressure differences between small for gestational age and appropriate for
      gestational age children are much more dependent on current body size.

PMID- 11967249
TI  - Familial aggregation of low-renin hypertension.
AB  - Low-renin hypertension, representing roughly one quarter of all essential
      hypertension, is widely recognized by distinct physiological features, including
      salt-sensitivity, diuretic- responsiveness, and a favorable natural history.
      Although certain demographic features including age, ethnicity, and diabetes
      mellitus predispose to low-renin hypertension, these factors account for only a
      minority of cases. We examined familial concordance for renin status in 119
      families with 257 hypertensive members. Low-renin was defined rigorously by
      plasma renin activity < or =0.69 ng angiotensin I/L per second, drawn when
      subjects had achieved balance after 5 to 7 days on a 10 mmol sodium diet and had
      stood upright for at least 1 hour. Given the prevalence of low-renin hypertension
      in our general population, low-renin hypertension was significantly more
      concordant among siblings than expected by chance (P=0.01). There were twice as
      many low-renin families as expected (10.9% versus 5.5%), in sharp contrast to the
      normal-renin state, in which the observed and expected were similar (61.0% versus
      58.6%). These results were independent of age, race, and gender. Variance in
      renin status attributable to family membership was 35%. Association studies were
      performed on 8 polymorphisms in 5 candidate genes, and significant association
      was confirmed with the G460W polymorphism of the adducin gene. Familial
      determinants, which are probably but not definitely genetic, contribute to the
      low-renin hypertension state.

PMID- 11967250
TI  - The T-786-->C mutation in endothelial nitric oxide synthase is associated with
      hypertension.
AB  - Although the pathogenic mechanisms involved in predisposing individuals to
      hypertension are not well defined, evidence is accumulating that suggests a
      strong genetic transmission. Animal studies and some clinical investigations have
      revealed that aberrant NO production may be an important contributing factor.
      Indeed, a missense mutation in the endothelial NO gene caused by a Glu298Asp
      alteration has been strongly associated with essential hypertension, coronary
      artery spasm, and myocardial infarction. Recently, another point mutation caused
      by a T-786-->C transition in the 5'-flanking region of the endothelial NO
      synthase gene has been identified and, like the Glu298Asp mutation, is associated
      with coronary artery spasm. The present study was conducted to determine the
      effect of the T-786-->C point mutation on hypertension. We investigated the
      interaction between the endothelial NO synthase T-786-->C polymorphism and blood
      pressure in a large (n=705) clinically healthy population. Allele frequencies for
      the T and C alleles were 62% and 38%, translating into 39%, 46% and 15% of the
      population having the T/T, T/C, and C/C genotypes, respectively, for the T-786-
      >C point mutation. Subjects with the C/C genotype had significantly higher
      systolic blood pressures and were 2.16(95% confidence interval, 1.3 to 3.7) more
      likely to be hypertensive. Therefore, the -786 C/C genotype in NO synthase is a
      significant contributing factor for increasing the risk of essential
      hypertension.

PMID- 11967251
TI  - Ultrasonic backscatter and serum marker of cardiac fibrosis in hypertensives.
AB  - Elevations in the serum concentration of the carboxy-terminal propeptide of
      procollagen type I (PIP) >127 microg/L have been found to predict severe
      myocardial fibrosis in hypertensive patients. This study was designed to assess
      whether ultrasonic reflectivity, evaluated by a real-time integrated backscatter
      analysis, was related to the severity of myocardial fibrosis as estimated by
      serum PIP. Thirty-four subjects were included in the study. Serum PIP was
      measured by specific radio immunoanalysis. Backscatter cyclic variation and
      maximal intensity were measured in 6 regions throughout the left ventricle. The
      subjects were divided into 3 groups: 14 normotensives with PIP <127 microg/L
      (group 1), 12 hypertensives with PIP <127 microg/L (group 2), and 8 hypertensives
      with PIP >127 microg/L (group 3). The highest cyclic variation was found in group
      1 and the lowest in group 3 (5.78+/-0.25 versus 4.70+/-0.33 dB, P<0.05), with
      intermediate values in group 2 (5.10+/-0.27 dB). No differences in maximal
      intensity were found among the 3 groups of subjects. Using receiver operating
      characteristics curves, we observed that a cutoff of 2.90 dB for cyclic variation
      measured in the apex provided 75% sensitivity and 63% specificity for predicting
      PIP >127 microg/L in hypertensives, with a relative risk of 2.50 (95% CI, 0.72 to
      34.70). These results show an association between diminished cyclic variation of
      backscatter and increased serum concentration of PIP in hypertension. Thus, the
      combination of these 2 parameters may be useful for the diagnosis of severe
      myocardial fibrosis associated with hypertension.

PMID- 11967252
TI  - Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE
      inhibitors.
AB  - Nonselective nonsteroidal anti-inflammatory agents have been shown to attenuate
      the antihypertensive efficacy of ACE inhibitors with average increases in
      systolic blood pressure (BP) of 5 to 10 mm Hg. Less is known about the specific
      cyclooxygenase-2 (COX-2) inhibitors now widely used for the treatment of
      arthritis. The objective of this study was to determine the effects of celecoxib
      compared with placebo on 24-hour BP levels in ACE inhibitor-treated patients with
      hypertension. This was a randomized, double-blind, placebo-controlled, parallel
      group clinical trial involving 178 men and women (mean age, 53 years) with
      essential hypertension who were treated and controlled with lisinopril
      monotherapy (10 to 40 mg daily). Baseline BP values were obtained using 24-hour
      ambulatory recordings. Patients received either celecoxib, 200 mg twice daily
      (twice the recommended dose for osteoarthritis) (n=91), or placebo (n=87) for 4
      weeks, and changes in the 24-hour BP, body weight, and clinical laboratory
      parameters were assessed. Mean changes from baseline in the 24-hour systolic and
      diastolic BP were 2.6/1.5+/-0.9/0.6 mm Hg on celecoxib versus 1.0/0.3+/-1/0.6 mm
      Hg on placebo (P=0.34 for systolic BP; P=0.45 for diastolic BP). The proportion
      of patients whose 24-hour BP increased by at least 5, 10, 15, or 20 mm Hg were
      also similar on celecoxib and placebo. No changes in body weight, serum
      creatinine, or potassium occurred in either group. Thus, these data demonstrate
      that high doses of celecoxib have no significant effect on the antihypertensive
      effect of the ACE inhibitor lisinopril. The placebo-subtracted changes observed
      in 24-hour BP (1.6/1.2 mm Hg) are less than what has been reported for
      nonselective nonsteroidal anti-inflammatory agents in ACE inhibitor-treated
      patients.

PMID- 11967253
TI  - Diagnostic value of the post-captopril test in primary aldosteronism.
AB  - Primary aldosteronism is a disorder with hypertension, hypokalemia, increased
      plasma aldosterone, and suppressed renin activity. A random plasma
      aldosterone/renin activity (PA/PRA) >65 (conventional units ratio [CUR] >30) has
      been proposed as a screening test. We have retrospectively determined the value
      of the post-captopril plasma aldosterone/renin activity (CAPT PA/PRA) test for
      the diagnosis of patients with primary aldosteronism whose PA/PRA was <65. We
      considered the CAPT PA/PRA test to be positive for primary aldosteronism if
      either the plasma aldosterone concentration did not drop below 0.33 nmol/L (12
      ng/dL) or the ratio was >26 (CUR >12). We found 6 patients with a random PA/PRA
      of 21 to 60 (CUR 10 to 28), yet with an abnormal post-captopril test criteria for
      primary aldosteronism. Five had an abnormal saline suppression test, and all 6
      were confirmed by a combination of diagnostic localization with computerized
      axial tomography, iodocholesterol scan, adrenal venous sampling, and/or surgery.
      Four had idiopathic adrenal hyperplasia, and 2 had an aldosterone-producing
      adenoma. One other patient had an abnormal random plasma aldosterone/renin
      activity ratio of 99 (CUR 46), a negative saline infusion study, and was
      determined to have essential hypertension. In summary, the CAPT PA/PRA, but not
      the random PA/PRA, correctly diagnosed 6 patients with primary aldosteronism in
      our institution. An additional patient with essential hypertension was
      incorrectly diagnosed as having primary aldosteronism by the PA/PRA test. We
      conclude that the simple addition of 25 mg of captopril, taken orally 2 hours
      before sampling, enhances the accuracy for diagnosing patients with primary
      aldosteronism.

PMID- 11967255
TI  - Nitric oxide and the regulation of arterial elasticity: right idea, wrong
      vascular bed?

PMID- 11967256
TI  - Dietary cholesterol fails to stimulate the human cholesterol 7alpha-hydroxylase
      gene (CYP7A1) in transgenic mice.
AB  - Dietary cholesterol has been shown to have a stimulatory effect on the murine
      cholesterol 7alpha-hydroxylase gene (Cyp7a1), but its effect on human cholesterol
      7alpha-hydroxylase gene (CYP7A1) expression in vivo is not known. A transgenic
      mouse strain harboring the human CYP7A1 gene and homozygous for the disrupted
      murine Cyp7a1 gene was created. Cholesterol feeding increased the expression of
      the endogenous modified Cyp7a1 allele but failed to stimulate the human CYP7A1
      transgene. In transfected hepatoma cells, 25-hydroxycholesterol increased murine
      Cyp7a1 gene promoter activity, whereas the human CYP7A1 gene promoter was
      unresponsive. Electrophoretic mobility shift assays demonstrated the interaction
      of the liver X receptor alpha (LXRalpha): retinoid X receptor (RXR) heterodimer,
      a transcription factor complex that is activated by oxysterols, with the murine
      Cyp7a1 gene promoter, whereas no binding to the human CYP7A1 gene promoter was
      detected. The results demonstrate that the human CYP7A1 gene is not stimulated by
      dietary cholesterol in the intact animal, and this is attributable to the
      inability of the CYP7A1 gene promoter to interact with LXRalpha:RXR.

PMID- 11967257
TI  - The immune modulator FTY720 targets sphingosine 1-phosphate receptors.
AB  - Immunosuppressant drugs such as cyclosporin have allowed widespread organ
      transplantation, but their utility remains limited by toxicities, and they are
      ineffective in chronic management of autoimmune diseases such as multiple
      sclerosis. In contrast, the immune modulating drug FTY720 is efficacious in a
      variety of transplant and autoimmune models without inducing a generalized
      immunosuppressed state and is effective in human kidney transplantation. FTY720
      elicits a lymphopenia resulting from a reversible redistribution of lymphocytes
      from circulation to secondary lymphoid tissues by unknown mechanisms. Using
      FTY720 and several analogs, we show now that FTY720 is phosphorylated by
      sphingosine kinase; the phosphorylated compound is a potent agonist at four
      sphingosine 1-phosphate receptors and represents the therapeutic principle in a
      rodent model of multiple sclerosis. Our results suggest that FTY720, after
      phosphorylation, acts through sphingosine 1-phosphate signaling pathways to
      modulate chemotactic responses and lymphocyte trafficking.

PMID- 11967258
TI  - The PYRIN-CARD protein ASC is an activating adaptor for caspase-1.
AB  - The PYRIN and CARD domains are members of the six-helix bundle death domain-fold
      superfamily that mediates assembly of large signaling complexes in the apoptotic
      and inflammatory signaling pathways. Here we show that the PYRIN-CARD protein ASC
      functions as a caspase-1-activating adaptor. ASC interacted specifically with
      procaspase-1 via CARD-CARD interactions and induced its oligomerization.
      Consistent with these results ectopic expression of full-length ASC, but not its
      isolated CARD or PYRIN domain, with procaspase-1 induced activation of procaspase
      1 and processing of pro-interleukin-1beta in transfected cells. Substitution of
      the PYRIN domain of ASC with an inducible FKBP12 oligomerization domain produced
      a molecule that can induce caspase-1 activation in response to stimulation with
      the oligomerization drug AP20187, suggesting that the PYRIN domain functions as
      an oligomerization domain, whereas the CARD domain functions as the effector
      domain in the caspase-1 activation pathway. Furthermore stable expression of an
      isolated CARD of ASC in THP-1 cells diminished interleukin-1beta generation in
      response to pro-inflammatory cytokines. These results indicate that ASC is
      involved in the caspase-1 signaling pathway by mediating the assembly of a
      caspase-1-inflammasome signaling complex in response to pro-inflammatory cytokine
      stimulation.

PMID- 11967259
TI  - Endothelial argininosuccinate synthase mRNA 5'-untranslated region diversity.
      Infrastructure for tissue-specific expression.
AB  - Based on the integral role that argininosuccinate synthase (AS) plays in the
      production of nitric oxide in vascular endothelial cells and urea in liver, an
      analysis was carried out to determine whether signals reside in the AS mRNA to
      account for tissue differences in AS function and location. Reverse transcriptase
      PCR and sequence analysis showed that the AS mRNA coding region was the same for
      both endothelial cells and liver; however, 5'-RACE analysis (rapid amplification
      of cDNA ends) identified AS mRNA species in endothelial cells in addition to a
      major 43-nucleotide (nt) 5'-untranslated region (UTR) AS mRNA with overlapping
      extended 5'-UTRs of 66 and 92 nt. Comparison to the genomic sequence immediately
      upstream of the reported transcription start site for the human and mouse AS gene
      suggested that expression of all three species of bovine endothelial AS mRNA are
      driven by a common promoter and that 5'-UTR diversity in endothelial cells
      results from three transcriptional initiation sites within exon 1. RNase
      protection analysis and real-time reverse transcriptase-PCR verified and
      quantitated the differential expression of the extended 5'-UTR species relative
      to the major 43-nt 5'-UTR AS mRNA. In vitro translation studies showed a less
      pronounced but similar discordant expression. Sequential deletions starting from
      the 5' terminus of the 92-nt 5'-UTR construct resulted in a corresponding
      increase in translational efficiency, but the most pronounced effect resulted
      from mutation of an upstream open reading frame, which restored translational
      efficiency of the 92-nt 5'-UTR AS mRNA. When the different AS mRNA 5'-UTRs,
      cloned in front of a luciferase reporter gene, were transfected into endothelial
      cells, the pattern of luciferase expression was nearly identical to that observed
      for the different 5'-UTR AS mRNAs in endothelial cells. Given the different roles
      ascribed for argininosuccinate synthase, urea versus NO production, these results
      suggest that sequence in the AS gene represented by position -92 to -43 nt from
      the translation start site in the extended AS mRNA 5'-UTRs plays an important
      role in differential and tissue-specific expression.

PMID- 11967260
TI  - Structural and enzymatic characterization of Drosophila Dm2-MMP, a membrane-bound
      matrix metalloproteinase with tissue-specific expression.
AB  - We report the isolation and characterization of a cDNA encoding Dm2-MMP, the
      second matrix metalloproteinase (MMP) identified in the Drosophila melanogaster
      genome. The cloned cDNA codes for a polypeptide of 758 residues that displays a
      domain organization similar to that of other MMPs, including signal peptide,
      propeptide, catalytic, and hemopexin domains. However, the structure of Dm2-MMP
      is unique because of the presence of an insertion of 214 amino acids between the
      catalytic and hemopexin domains that is not present in any of the previously
      described MMPs. Dm2-MMP also contains a C-terminal extension predicted to form a
      cleavable glycosylphosphatidylinositol anchor site. Western blot and
      immunofluorescence analysis of S2 cells transfected with the isolated cDNA
      confirmed that Dm2-MMP is localized at the cell surface. Production of the
      catalytic domain of Dm2-MMP in Escherichia coli and analysis of its enzymatic
      activity revealed that this proteinase cleaves several synthetic peptides used
      for analysis of vertebrate MMPs. This proteolytic activity was abolished by MMP
      inhibitors such as BB-94, confirming that the isolated cDNA codes for an
      enzymatically active metalloproteinase. Reverse transcription-PCR analysis showed
      that Dm2-MMP is expressed at low levels in all of the developmental stages of
      Drosophila as well as in adult flies. However, detailed in situ hybridization at
      the larval stage revealed a strong tissue-specific expression in discrete regions
      of the brain and eye imaginal discs. According to these results, we propose that
      Dm2-MMP plays both general proteolytic functions during Drosophila development
      and in adult tissues and specific roles in eye development and neural tissues
      through the degradation and remodeling of the extracellular matrix.

PMID- 11967261
TI  - Cell surface accumulation of a truncated transmembrane prion protein in Gerstmann
      Straussler-Scheinker disease P102L.
AB  - A familial prion disorder with a proline to leucine substitution at residue 102
      of the prion protein (PrP(102L)) is typically associated with protease-resistant
      PrP fragments (PrP(Sc)) in the brain parenchyma that are infectious to recipient
      animals. When modeled in transgenic mice, a fatal neurodegenerative disease
      develops, but, unlike the human counterpart, PrP(Sc) is lacking and transmission
      to recipient animals is questionable. Alternate mice expressing a single copy of
      PrP(102L) (mouse PrP(101L)) do not develop spontaneous disease, but show dramatic
      susceptibility to PrP(Sc) isolates from different species. To understand these
      discrepant results, we studied the biogenesis of human PrP(102L) in a cell model.
      Here, we report that cells expressing PrP(102L) show decreased expression of the
      normal 18-kDa fragment on the plasma membrane. Instead, a 20-kDa fragment,
      probably derived from transmembrane PrP ((Ctm)PrP), accumulates on the cell
      surface. Because the 20-kDa fragment includes an amyloidogenic region of PrP that
      is disrupted in the 18-kDa form, increased surface expression of 20-kDa fragment
      may enhance the susceptibility of these cells to PrP(Sc) infection by providing
      an optimal substrate, or by amplifying the neurotoxic signal of PrP(Sc). Thus,
      altered susceptibility of PrP(101L) mice to exogenous PrP(Sc) may be mediated by
      the 20-kDa (Ctm)PrP fragment, rather than PrP(102L) per se.

PMID- 11967262
TI  - Functional importance of the 3'-terminal adenosine of tRNA in ribosomal
      translation.
AB  - The universally conserved 3'-terminal CCA sequence of tRNA interacts with large
      ribosomal subunit RNA during translation. The functional importance of the
      interaction between the 3'-terminal nucleotide of tRNA and the ribosome was
      studied in vitro using mutant in vitro transcribed tRNA(Val) A76G. Val-tRNA(CCG)
      does not support polypeptide synthesis on poly(GUA) as a message. However, in a
      co-translation system, where Val-tRNA(CCG) represented only a small fraction of
      total Val-tRNA, the mutant tRNA is able to transfer valine into a polypeptide
      chain, albeit at a reduced level. The A76G mutation does not affect binding of
      Val- or NAcVal-tRNA(CCG) to the A- or P-sites as shown by efficient peptide bond
      formation, although the donor activity of the mutant NAcVal-tRNA(CCG) in the
      peptidyl transfer reaction is slightly reduced compared with wild-type NAcVal
      tRNA. Translocation of 3'-CCG-tRNA from the P- to the E-site is not significantly
      influenced. However, the A76G mutation drastically inhibits translocation of
      peptidyl-tRNA G(76) from the ribosomal A-site to the P-site, which apparently
      explains its failure to support cell-free protein synthesis. Our results indicate
      that the identity of the 3'-terminal nucleotide of tRNA is critical for tRNA
      movement in the ribosome.

PMID- 11967263
TI  - Expression and characterization of GSK-3 mutants and their effect on beta-catenin
      phosphorylation in intact cells.
AB  - Glycogen synthase kinase-3 (GSK-3) is a serine-threonine kinase that is involved
      in multiple cellular signaling pathways, including the Wnt signaling cascade
      where it phosphorylates beta-catenin, thus targeting it for proteasome-mediated
      degradation. Unlike phosphorylation of glycogen synthase, phosphorylation of beta
      catenin by GSK-3 does not require priming in vitro, i.e. it is not dependent on
      the presence of a phosphoserine, four residues C-terminal to the GSK-3
      phosphorylation site. Recently, a means of dissecting GSK-3 activity toward
      primed and non-primed substrates has been made possible by identification of the
      R96A mutant of GSK-3beta. This mutant is unable to phosphorylate primed but can
      still phosphorylate unprimed substrates (Frame, S., Cohen, P., and Biondi R. M.
      (2001) Mol. Cell 7, 1321-1327). Here we have investigated whether phosphorylation
      of Ser(33), Ser(37), and Thr(41) in beta-catenin requires priming through prior
      phosphorylation at Ser(45) in intact cells. We have shown that the Arg(96) mutant
      does not induce beta-catenin degradation but instead stabilizes beta-catenin,
      indicating that it is unable to phosphorylate beta-catenin in intact cells.
      Furthermore, if Ser(45) in beta-catenin is mutated to Ala, beta-catenin is
      markedly stabilized, and phosphorylation of Ser(33), Ser(37), and Thr(41) in beta
      catenin by wild type GSK-3beta is prevented in intact cells. In addition, we have
      shown that the L128A mutant, which is deficient in phosphorylating Axin in vitro,
      is still able to phosphorylate beta-catenin in intact cells although it has
      reduced activity. Mutation of Tyr(216) to Phe markedly reduces the ability of GSK
      3beta to phosphorylate and down-regulate beta-catenin. In conclusion, we have
      found that the Arg(96) mutant has a dominant-negative effect on GSK-3beta
      dependent phosphorylation of beta-catenin and that targeting of beta-catenin for
      degradation requires prior priming through phosphorylation of Ser(45).

PMID- 11967264
TI  - Coupling of cell energetics with membrane metabolic sensing. Integrative
      signaling through creatine kinase phosphotransfer disrupted by M-CK gene knock
      out.
AB  - Transduction of metabolic signals is essential in preserving cellular
      homeostasis. Yet, principles governing integration and synchronization of
      membrane metabolic sensors with cell metabolism remain elusive. Here, analysis of
      cellular nucleotide fluxes and nucleotide-dependent gating of the ATP-sensitive
      K+ (K(ATP)) channel, a prototypic metabolic sensor, revealed a diffusional
      barrier within the submembrane space, preventing direct reception of cytosolic
      signals. Creatine kinase phosphotransfer, captured by 18O-assisted 31P NMR,
      coordinated tightly with ATP turnover, reflecting the cellular energetic status.
      The dynamics of high energy phosphoryl transfer through the creatine kinase relay
      permitted a high fidelity transmission of energetic signals into the submembrane
      compartment synchronizing K(ATP) channel activity with cell metabolism. Knock-out
      of the creatine kinase M-CK gene disrupted signal delivery to K(ATP) channels and
      generated a cellular phenotype with increased electrical vulnerability. Thus, in
      the compartmentalized cell environment, phosphotransfer systems shunt diffusional
      barriers and secure regimented signal transduction integrating metabolic sensors
      with the cellular energetic network.

PMID- 11967265
TI  - ADAM13 disintegrin and cysteine-rich domains bind to the second heparin-binding
      domain of fibronectin.
AB  - ADAM13 is a member of the disintegrin and metalloprotease protein family that is
      expressed on cranial neural crest cells surface and is essential for their
      migration. ADAM13 is an active protease that can cleave fibronectin in vitro and
      remodel a fibronectin substrate in vivo. Using a recombinant secreted protein
      containing both disintegrin and cysteine-rich domains of ADAM13, we show that
      this "adhesive" region of the protein binds directly to fibronectin. Fibronectin
      fusion proteins corresponding to the various functional domains were used to
      define the second heparin-binding domain as the ADAM13 binding site. Mutation of
      the syndecan-binding site (PPRR --> PPTM) within this domain abolishes binding of
      the recombinant disintegrin and cysteine-rich domains of ADAM13. We further show
      that the adhesive disintegrin and cysteine-rich domain of ADAM13 can promote cell
      adhesion via beta(1) integrins. This adhesion requires integrin activation and
      can be prevented by antibodies to the cysteine-rich domain of ADAM13 and beta(1)
      integrin. Finally, wild type, but not the E/A mutant of ADAM13 metalloprotease
      domain, can be shed from the cell surface, releasing the metalloprotease domain
      associated with the disintegrin and cysteine-rich domains. This suggests that
      ADAM13 shedding may involve its own metalloprotease activity and that the
      released protease may interact with both integrins and extracellular matrix
      proteins.

PMID- 11967267
TI  - Substrate-activated zinc binding of metallo-beta -lactamases: physiological
      importance of mononuclear enzymes.
AB  - We have investigated the influence of substrate binding on the zinc ion affinity
      of representatives from the three metallo-beta-lactamase subclasses, B1 (BcII
      from Bacillus cereus and BlaB from Chryseobacterium meningosepticum), B2 (CphA
      from Aeromonas hydrophila), and B3 (L1 from Stenotrophomonas maltophilia). By
      competition experiments with metal-free apoenzymes and chromophoric zinc
      chelators or EDTA, we determined the dissociation constants in the absence and
      presence of substrates. For the formation of the monozinc enzymes we determined
      constants of 1.8, 5.1, 0.007, and 2.6 nm in the absence and 13.6, 1.8, 1.2, and
      5.7 pm in the presence of substrates for BcII, BlaB, CphA, and L1, respectively.
      A second zinc ion binds in the absence (presence) of substrates with considerably
      higher dissociation constants, namely 1.8 (0.8), 0.007 (0.025), 50 (1.9), and
      0.006 (0.12) microm for BcII, BlaB, CphA, and L1, respectively. We have concluded
      that the apo form might be the prevailing state of most of the metallo-beta
      lactamases under physiological conditions in the absence of substrates. Substrate
      availability induces a spontaneous self-activation due to a drastic decrease of
      the dissociation constants, resulting in the formation of active mononuclear
      enzymes already at picomolar free zinc ion concentrations. In the presence of
      substrates, the binuclear state of the enzymes only exists at unphysiologic high
      zinc concentrations and might be of no biological relevance. From the competition
      experiments with EDTA it is further concluded that the reactivation rate does not
      depend on the pool of free zinc ions but proceeds via the EDTA-Zn(II)-enzyme
      ternary complexes.

PMID- 11967266
TI  - The hypertrophic response in C2C12 myoblasts recruits the G1 cell cycle
      machinery.
AB  - Hypertrophy occurs in postmitotic muscle as an adaptive response to various
      physiological and pathological stresses. Studies in vascular smooth muscle cells
      and primary cardiomyocytes suggest that angiotensin II-mediated hypertrophy
      activates signaling pathways associated with cell proliferation. Regulation of
      cyclin-dependent kinase (Cdk)-cyclin activities is essential to cell size control
      in lower eukaryotes, yet their role in the hypertrophic response in muscle is
      incompletely understood. We describe an in vitro model of hypertrophy in C2C12
      skeletal myoblasts and demonstrate that induction of hypertrophy involves
      transient activation of Cdk4, subsequent phosphorylation of Rb, and release of
      HDAC1 from the Rb inhibitory complex. We also demonstrate that E2F-1 becomes
      transcriptionally active yet remains associated with Rb. We propose a model
      whereby partial inactivation of the Rb complex leads to derepression of a subset
      of E2F-1 targets necessary for cell growth without division during hypertrophy.

PMID- 11967268
TI  - Structural studies on the synchronization of catalytic centers in glutamate
      synthase.
AB  - The complex iron-sulfur flavoprotein glutamate synthase (GltS) plays a prominent
      role in ammonia assimilation in bacteria, yeasts, and plants. GltS catalyzes the
      formation of two molecules of l-glutamate from 2-oxoglutarate and l-glutamine via
      intramolecular channeling of ammonia. GltS has the impressive ability of
      synchronizing its distinct catalytic centers to avoid wasteful consumption of l
      glutamine. We have determined the crystal structure of the ferredoxin-dependent
      GltS in several ligation and redox states. The structures reveal the crucial
      elements in the synchronization between the glutaminase site and the 2
      iminoglutarate reduction site. The structural data combined with the catalytic
      properties of GltS indicate that binding of ferredoxin and 2-oxoglutarate to the
      FMN-binding domain of GltS induce a conformational change in the loop connecting
      the two catalytic centers. The rearrangement induces a shift in the catalytic
      elements of the amidotransferase domain, such that it becomes activated. This
      machinery, over a distance of more than 30 A, controls the ability of the enzyme
      to bind and hydrolyze the ammonia-donating substrate l-glutamine.

PMID- 11967269
TI  - Saccharomyces cerevisiae acyl-CoA oxidase follows a novel, non-PTS1, import
      pathway into peroxisomes that is dependent on Pex5p.
AB  - The peroxisomal protein acyl-CoA oxidase (Pox1p) of Saccharomyces cerevisiae
      lacks either of the two well characterized peroxisomal targeting sequences known
      as PTS1 and PTS2. Here we demonstrate that peroxisomal import of Pox1p is
      nevertheless dependent on binding to Pex5p, the PTS1 import receptor. The
      interaction between Pex5p and Pox1p, however, involves novel contact sites in
      both proteins. The interaction region in Pex5p is located in a defined area of
      the amino-terminal part of the protein outside of the tetratricopeptide repeat
      domain involved in PTS1 recognition; the interaction site in Pox1p is located
      internally and not at the carboxyl terminus where a PTS1 is normally found. By
      making use of pex5 mutants that are either specifically disturbed in binding of
      PTS1 proteins or in binding of Pox1p, we demonstrate the existence of two
      independent, Pex5p-mediated import pathways into peroxisomes in yeast as follows:
      a classical PTS1 pathway and a novel, non-PTS1 pathway for Pox1p.

PMID- 11967271
TI  - The role of stem cells in skeletal and cardiac muscle repair.
AB  - In postnatal muscle, skeletal muscle precursors (myoblasts) can be derived from
      satellite cells (reserve cells located on the surface of mature myofibers) or
      from cells lying beyond the myofiber, e.g., interstitial connective tissue or
      bone marrow. Both of these classes of cells may have stem cell properties. In
      addition, the heretical idea that post-mitotic myonuclei lying within mature
      myofibers might be able to re-form myoblasts or stem cells is examined and
      related to recent observations for similar post-mitotic cardiomyocytes. In adult
      hearts (which previously were not considered capable of repair), the role of
      replicating endogenous cardiomyocytes and the recruitment of other (stem) cells
      into cardiomyocytes for new cardiac muscle formation has recently attracted much
      attention. The relative contribution of these various sources of precursor cells
      in postnatal muscles and the factors that may enhance stem cell participation in
      the formation of new skeletal and cardiac muscle in vivo are the focus of this
      review. We concluded that, although many endogenous cell types can be converted
      to skeletal muscle, the contribution of non-myogenic cells to the formation of
      new postnatal skeletal muscle in vivo appears to be negligible. Whether the
      recruitment of such cells to the myogenic lineage can be significantly enhanced
      by specific inducers and the appropriate microenvironment is a current topic of
      intense interest. However, dermal fibroblasts appear promising as a realistic
      alternative source of exogenous myoblasts for transplantation purposes. For heart
      muscle, experiments showing the participation of bone marrow-derived stem cells
      and endothelial cells in the repair of damaged cardiac muscle are encouraging.

PMID- 11967272
TI  - Transmissible spongiform encephalopathy diagnosis using PrPsc
      immunohistochemistry on fixed but previously frozen brain samples.
AB  - The histological diagnosis of transmissible spongiform encephalopathies (TSEs),
      such as scrapie and bovine spongiform encephalopathy (BSE), relies on
      identification in the brain of spongiosis, gliosis, and neuron loss without
      inflammatory lesions. Because of its sensitivity, immunohistochemistry of
      abnormal prion protein (PrPsc) is of great help in this diagnosis and can be used
      on its own or complementary to the biochemical detection of PrPsc. However, in
      some cases no formalin-fixed material is available, rendering its use as a
      complementary method impossible. For that purpose, we studied the possibility of
      detecting PrPsc immunohistochemically in fixed brain samples that had been
      previously frozen and used for Western blotting analysis. We compared freshly and
      fixed-frozen brain samples originating from the same sheep, either affected or
      unaffected with scrapie. We also studied fixed-frozen brain samples from scrapie
      affected goats and from cows showing BSE. We showed that in all the species
      tested, despite damage to the histological structures, PrPsc was still detectable
      in the fixed-frozen brain sections without unspecific background staining.
      Notwithstanding the limited number of cases thus far analyzed, we have already
      demonstrated the possibility of using PrPsc immunohistochemistry on fixed-frozen
      brain samples with very good efficacy, thus rendering possible its use for
      diagnostic purposes in TSEs.

PMID- 11967274
TI  - Apolipoprotein B is synthesized in selected human non-hepatic cell lines but not
      processed into mature lipoprotein.
AB  - We studied apolipoprotein B100 (apoB) metabolism in a series of non-hepatic cell
      lines (HT29 colon adenocarcinoma, HeLa cervical epithelioid carcinoma, and
      1321N1J astrocytoma human cell lines) and in the human hepatoma cell line HepG2.
      ApoB mRNA was detected by reverse transcription polymerase chain reaction in each
      non-hepatic cell line. ApoB was detected in HepG2 cells by immunoprecipitation,
      Western blotting, and immunocytochemistry using a polyclonal anti-human low
      density lipoprotein (LDL) antibody, an anti-human apoB peptide antibody, and
      several monoclonal anti-apoB antibodies. ApoB was identified in the three non
      hepatic cell lines by each method using the anti-apoB peptide and monoclonal
      antibodies, but not with the anti-LDL antibody. Immunocytochemistry indicated
      that epitopes of apoB were evident throughout the endoplasmic reticulum, and gel
      mobility of newly labeled apoB and immunoblot with anti-ubiquitin showed that
      apoB was highly ubiquinated in non-hepatic cells. The observations that apoB is
      synthesized in non-hepatic cell lines but never recognized by the anti-LDL
      antibody suggests that apoB is not processed into a nascent lipoprotein in these
      cells. Immunocytochemical localization of apoB epitopes at many locations
      throughout non-hepatic cells raises the exciting possibility that apoB can be
      used for other purposes in these cells.

PMID- 11967273
TI  - Localization of caveolin 1 in aortic valve endothelial cells using antigen
      retrieval.
AB  - Ultrastructural analysis of aortic valve endothelial cells subjected to growth
      arrest revealed many vesicles defined as caveolae by the localization of
      caveolin. Translocation of caveolin after exposure to oxidized LDL suggests that
      the localization of caveolin may be a valuable tool to study models of early
      atherogenesis. In this study, several antigen retrieval protocols were tested in
      osmium-fixed and Spurr-embedded cells to determine the optimal method of antigen
      retrieval in our model system. SDS produced the most consistent labeling pattern.
      A quantitative evaluation revealed that SDS significantly increased the labeling
      density in Spurr-embedded cells. The labeling pattern appeared as clusters of
      gold particles, 15-40 nm in diameter, that were associated with membranes of a
      similar size which may represent the neck region of the caveolae.

PMID- 11967275
TI  - Differences in postmortem stability of sex steroid receptor immunoreactivity in
      rat brain.
AB  - Difficulties in demonstrating sex steroid receptors in the human brain by
      immunohistochemistry (IHC) may depend on postmortem delay and a long fixation
      time. The effect of different postmortem times was therefore studied in rat brain
      kept in the skull at room temperature for 0, 6, or 24 hr after death. After a
      long fixation for 20 days, hypothalami were embedded in paraffin and sections
      were immunohistochemically stained for androgen receptor (AR), estrogen receptor
      alpha (ER), or progesterone receptor (PR). Retrieving the antigenic sites by
      microwave pretreatment was essential to obtain successful IHC in all groups
      studied. In general, immunoreactivity was restricted to the cell nuclei. However,
      the intensity of the staining appeared to be strongly dependent on the different
      receptor antigens and postmortem time. Both AR and ER but not PR immunoreactivity
      were decreased after immersion-fixation compared to the perfused sections at time
      point zero. In brains fixed by immersion, all three receptors decreased gradually
      with increasing postmortem time, and ER became hardly detectable after 24 hr
      postmortem. The results of these experiments show that, with the protocol used,
      postmortem variables and lengthy fixation do not, in principle, prevent sex
      steroid receptor IHC in human material. The outcome of the immunostaining,
      however, might be strongly dependent on the epitopes and/or antibody used.

PMID- 11967276
TI  - Immunolocalization of surfactant protein-D (SP-D) in human fetal, newborn, and
      adult tissues.
AB  - Immunoreactive surfactant protein-D (SP-D) was assessed in human fetal, newborn,
      and adult tissues. In the fetal lung, SP-D was detected on airway surfaces by 10
      weeks' gestation, staining increasing in the distal airways, decreasing in the
      proximal conducting airways with advancing gestation. In lungs from near-term
      infants and adults, SP-D was detected in Type II cells, serous cells of
      tracheobronchial glands, and subsets of cells lining peripheral airways.
      Immunostaining was decreased or absent in areas of lungs of neonates after injury
      to Type II cells, infection, or hemorrhage and was decreased in collapsed or
      unseptated airways from older infants with bronchopulmonary dysplasia. SP-D was
      also detected in many organs at all ages. SP-D was readily detected in epithelial
      cells and luminal material in lacrimal glands, salivary glands, pancreas, bile
      ducts, renal tubules, esophageal muscle and glands, parietal cells of the
      stomach, crypts of Lieberkuhn, sebaceous and eccrine sweat glands, Von Ebner's
      glands, endocervical glands, seminal vesicles, adrenal cortex, myocardium, and
      anterior pituitary gland. SP-D is a widely distributed member of the "collectin"
      family of polypeptides secreted onto luminal surfaces by epithelial cells lining
      ducts of many organs, where it likely plays a role in innate host defense.

PMID- 11967277
TI  - Cell type-specific localization of human cardiac S1P receptors.
AB  - Sphingosine 1-phosphate (S1P), which derives from the metabolism of
      sphingomyelin, is mainly synthesized, stored, and released from platelets after
      activation by physiological and pathophysiological events. S1P acts in
      cardiovascular tissues through cell surface G-protein-coupled receptors of the
      endothelial differentiation gene (EDG) family, i.e., EDG1, EDG3 and EDG5. The aim
      of the present study was to assess the precise distribution of EDG1, EDG3, and
      EDG5 receptors expressed in human cardiovascular tissues to investigate their
      respective physiological implication. When assessed by Northern blots, EDG1,
      EDG3, and EDG5 displayed wide expression levels in decreasing order,
      respectively. In particular, EDG3 was mainly detected in the aorta. Detailed
      analysis by in situ hybridization (ISH) and immunohistochemistry (IHC) revealed
      strong EDG1 expression in cardiomyocytes and in endothelial cells of cardiac
      vessels. In cardiomyocytes, the EDG1 receptor is likely to be co-expressed with
      EDG3 and EDG5, although EDG1 exhibits the most prominent expression pattern.
      Unlike EDG3 and EDG5, which are expressed in the smooth muscle cell layer of the
      human aorta, no signal corresponding to EDG1 expression could be detected in the
      aorta. Moreover, only EDG3 expression was also found in smooth muscle cells of
      cardiac vessels. The present results provide new insight into the expression
      pattern of S1P receptors in human cardiovascular tissues, indicating a
      differential pattern of expression for these receptors in human vessels.

PMID- 11967278
TI  - Immunocytochemical detection of neuronal nitric oxide synthase (nNOS)-IR in
      embryonic rat stomach between days 13 and 21 of gestation.
AB  - In this study, the localization and appearance of neuronal nitric oxide synthase
      immunoreactive (nNOS-IR) nerve cells and their relationships with the developing
      gastric layers were studied by immunocytochemistry techniques and light
      microscopy in embryonic rat stomach. The stomachs of Wistar rat embryos aged 13
      21 days were used. The first nerve cells containing nNOS-IR were seen on
      embryonic Day 14. The occurrence of mesenchymal cell condensation near nNOS-IR
      neuroblasts on embryonic Day 15 may reflect an active nerve element-specific
      mesenchymal cell induction causing the morphogenesis of muscle cells. Similarly,
      the appearance of glandular structures after nNOS-IR neuroblasts, on embryonic
      Day 18, suggests that the epithelial differentiation may depend on inputs coming
      from nNOS-IR neuroblasts, as well as other factors. Observation of nNOS-IR nerve
      fibers on embryonic Day 21 demonstrates that at this stage they contribute to
      nonadrenergic noncholinergic relaxation. In conclusion, depending on this study's
      results, it can be said that cells and tissues might be affected by NO secreted
      by nNOS-IR nerve cells during the development and differentiation of embryonic
      rat stomach.

PMID- 11967279
TI  - Accumulation of the amyloid-beta precursor protein in multivesicular body-like
      organelles.
AB  - It has been suggested that the successive proteolytic events leading to the
      production of the amyloid-beta protein from its precursor may take place at
      different intracellular locations. Using cultured human leptomeningeal smooth
      muscle cells and brain pericytes, we modulated the intracellular localization of
      the amyloid-beta precursor protein (APP) to study possible effects on its
      processing. By using immunofluorescence and immunoelectron microscopy we
      demonstrated that, under normal conditions, the APP is found in small
      intracellular vesicles, some of which were characterized as lysosomes. Both the
      cytokine interferon-gamma and the lysosomotropic drug chloroquine, but not the
      cytokines interleukin (IL)-1, IL-6, or tumor necrosis factor-alpha (TNF-alpha),
      induced an accumulation of APP in newly formed multivesicular body-like
      organelles. The secretion of the amyloid-beta precursor protein was slightly
      reduced by interferon-gamma or chloroquine. Double-labeling and tracer molecule
      uptake experiments showed that the multivesicular body-like organelles were part
      of the endocytic pathway. Our findings suggest that the multivesicular body-like
      organelles function as an intermediate organelle in the intracellular trafficking
      of the APP. Accumulation of the APP in this organelle is reflected by its reduced
      secretion from the cell.

PMID- 11967280
TI  - Cell type-specific expression of the Mas proto-oncogene in testis.
AB  - The Mas proto-oncogene encodes a G-protein-coupled receptor with the common seven
      transmembrane domains and may be involved in the actions of angiotensins. Because
      Mas is highly expressed in testis, we investigated the cell type-specificity and
      the onset of expression of the gene in this organ. Using an RNase protection
      assay, it could be shown that neither whole testes nor cultured Sertoli and
      Leydig cells of 12-day-old mice express Mas mRNA. Mas expression is first
      detected in 18-day-old mice and thereafter increases continuously until 6 months
      of age. By in situ hybridization, the expression could be localized to Leydig
      cells and Sertoli cells, the signals being much more pronounced in the former. A
      weak signal was detected in primary spermatocytes. The strong ontogenetically
      controlled and cell type-specific expression of this membrane-bound receptor in
      testis implicates a role for the Mas proto-oncogene in testis maturation and
      function.

PMID- 11967281
TI  - A monoclonal antibody to visualize PtdIns(3,4,5)P(3) in cells.
AB  - Phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] is a second
      messenger produced in response to agonist stimulation. Traditionally,
      visualization of phosphoinositide polyphosphates (PtdInsP(n)) in living cells is
      accomplished using chimeric green fluorescent protein (GFP)-pleckstrin homology
      (PH) domain proteins, while PtdInsP(n) quantitation is accomplished by extraction
      and separation of radiolabeled cellular PtdInsP(n)s. Here we describe preparation
      of a covalent protein-PtdIns(3,4,5)P(3) immunogen, characterization of binding
      selectivity of an anti-PtdIns(3,4,5)P(3) IgM, and immunodetection of
      PtdIns(3,4,5)P(3) in stimulated mammalian cells. This antibody has greater than
      three orders of magnitude selectivity for binding PtdIns(3,4,5)P(3) relative to
      its precursor, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)), and is
      therefore optimal for studies of cell function. The immunodetection in platelet
      derived growth factor (PDGF)-stimulated NIH 3T3 cells was benchmarked against
      HPLC analysis of [3H]-myo-inositol-labeled cellular PtdInsP(n)s. In addition, the
      changes in subcellular amounts and localizations of both PtdIns(3,4,5)P(3) and
      PtdIns(4,5)P(2) in stimulated NIH 3T3 fibroblasts and human neutrophils were
      observed by immunofluorescence. In insulin- or PDGF-stimulated fibroblasts,
      PtdIns(3,4,5)P(3) levels increased in the cytoplasm, peaking at 10 min. In
      contrast, increases in the PtdIns(4,5)P(2) levels were detected in nuclei,
      corresponding to the production of new substrate following depletion by
      phosphoinositide (PI) 3-kinase.

PMID- 11967282
TI  - Ganglion cells and topographically related nerves in the vallate papilla/von
      Ebner gland complex.
AB  - Ganglion cells and topographically related nerves in the vallate papilla/von
      Ebner gland complex were investigated in rat tongue by cytochemical,
      immunocytochemical, and ultrastructural methods to evaluate the possible presence
      of different neuronal subpopulations. Immunostaining for neurofilaments and
      protein gene product 9.5 revealed ganglionic cell bodies and nerve fibers. A
      large part of the neurons were positive at immunostaining for neuronal nitric
      oxide synthase (NOS), vesicular acetylcholine transporter (VAChT), or vasoactive
      intestinal peptide (VIP). A small subset of nerve fibers revealed
      immunoreactivity for cholecystokinin. Axons traveling under the lingual
      epithelium were evidenced by their content of calcitonin gene-related peptide
      (CGRP) or substance P (SP). Cell bodies positive for SP or CGRP were not
      detected. Using methods of co-localization, three different neuronal classes were
      detected. The main population was composed of AChE/NADPH-diaphorase (NADPHd)
      positive cells. Small groups of acetylcholine esterase (AChE)-positive/NADPHd
      negative cells were visible. Isolated neurons were AChE-negative/NADPHd-positive.
      The results of co-localization experiments for VAChT/NOS were consistent with
      those obtained by cytochemical co-localization of AChE and NADPHd. Experiments of
      co-localization for peptidergic and nitrergic structures revealed CGRP- and SP
      immunoreactive fibers in the vallate papilla/von Ebner gland ganglion. In
      conclusion, the results demonstrated in the VP/VEG complex peptidergic,
      cholinergic, and nitrergic neurons. The presence of different neuronal subclasses
      suggests that a certain degree of functional specialization may exist.

PMID- 11967283
TI  - New insights into muscle fiber types in the pig.
AB  - The accurate classification of skeletal muscle fiber types according to myosin
      heavy chain (MyHC) polymorphism remains a difficult task in the pig. Combined
      myofibrillar ATPase and metabolic enzyme histochemistry, in situ hybridization,
      and immunocytochemistry were performed on serial transverse sections of pig
      longissimus (L) and rhomboideus (R) muscles at 100 kg body weight to give a new
      insight into muscle fiber typing in the pig. Several monoclonal antibodies (MAbs)
      either specific for a single MyHC (I, IIa, or IIb) or of multiple MyHCs (IIa +
      IIx or I + IIx + IIb) were used. No monospecific IIx antibody was available for
      the pig. All three adult Type II isoforms were expressed in the white L muscle,
      whereas no IIb was observed in the red R muscle, which was confirmed using RNase
      protection analysis. In most fibers, the distribution of the transcripts closely
      matched that of the corresponding proteins. When observed, co-expression of MyHCs
      mostly occured for IIx and IIb in L muscle, and was more common at the protein
      (11.5%) than at the mRNA (2.2%) level. A minor proportion of myofibers showed a
      mismatch between MyHC mRNA and protein. According to the type grouping
      distribution of myofibers encountered in pig muscle, MyHC isoform expression
      followed the rank order of I-->IIa-->IIx-->IIb from the center to the periphery
      of the islets, concomitantly with a decrease in oxidative metabolism and an
      increase in fiber size. The developmental origin and functional significance of
      the type grouping distribution are discussed.

PMID- 11967284
TI  - The fluorescent probe Bodipy-FL-verapamil is a substrate for both P-glycoprotein
      and multidrug resistance-related protein (MRP)-1.
AB  - Several fluorescent probes have been used in functional studies to analyze drug
      transport in multidrug-resistant cells by fluorescent microscopy. Because many of
      these molecules have some drawbacks, such as toxicity, nonspecific background, or
      accumulation in mitochondria, new fluorescent compounds have been proposed as
      more useful tools. Among these substances, Bodipy-FL-Verapamil, a fluorescent
      conjugate of the drug efflux blocker verapamil, has been used to study P
      glycoprotein activity in different cell types. In this study we tested by
      fluorescent microscopy the accumulation of Bodipy-FL-Verapamil in cell lines that
      overexpress either P-glycoprotein (P-gp) or multidrug resistance-related protein
      1 (MRP1). Expression of P-gp and MRP1 was evaluated at the mRNA level by RT-PCR
      technique and at the protein level by flow cytometric analysis using C219 and MRP
      m6 monoclonal antibodies. Results indicate that Bodipy-FL-Verapamil is actually a
      substrate for both proteins. As a consequence, any conclusion about P-gp activity
      obtained by the use of Bodipy-FL-Verapamil as fluorescent tracer should be
      interpreted with caution.

PMID- 11967285
TI  - Viral late domains.

PMID- 11967286
TI  - Kaposi's sarcoma-associated herpesvirus OX2 glycoprotein activates myeloid
      lineage cells to induce inflammatory cytokine production.
AB  - Kaposi's sarcoma is an inflammatory cytokine-mediated angioproliferative disease
      which is triggered by infection by Kaposi's sarcoma-associated herpesvirus
      (KSHV). KSHV contains an open reading frame, K14, that has significant homology
      with cellular OX2, designated viral OX2 (vOX2). In this report, we demonstrate
      that vOX2 encodes a glycosylated cell surface protein with an apparent molecular
      mass of 55 kDa. Purified glycosylated vOX2 protein dramatically stimulated
      primary monocytes, macrophages, and dendritic cells to produce the inflammatory
      cytokines interleukin 1beta (IL-1beta), IL-6, monocyte chemoattractant protein 1,
      and TNF-alpha. Furthermore, expression of vOX2 on B lymphocytes stimulated
      monocytes to produce inflammatory cytokines in mixed culture. These results
      demonstrate that like its cellular counterpart, vOX2 targets myeloid-lineage
      cells, but unlike cellular OX2, which delivers a restrictive signal, KSHV vOX2
      provides an activating signal, resulting in the production of inflammatory
      cytokines. Thus, this is a novel viral strategy where KSHV has acquired the
      cellular OX2 gene to induce inflammatory cytokine production, which potentially
      promotes the cytokine-mediated angiogenic proliferation of KSHV-infected cells.

PMID- 11967287
TI  - Epstein-Barr virus nuclear antigen 3C and prothymosin alpha interact with the
      p300 transcriptional coactivator at the CH1 and CH3/HAT domains and cooperate in
      regulation of transcription and histone acetylation.
AB  - The Epstein-Barr virus nuclear antigen 3C (EBNA3C), encoded by Epstein-Barr virus
      (EBV), is essential for mediating transformation of human B lymphocytes. Previous
      studies demonstrated that EBNA3C interacts with a small, nonhistone, highly
      acidic, high-mobility group-like nuclear protein prothymosin alpha (ProT(alpha))
      and the transcriptional coactivator p300 in complexes from EBV-infected cells.
      These complexes were shown to be associated with histone acetyltransferase (HAT)
      activity in that they were able to acetylate crude histones in vitro. In this
      report we show that ProT(alpha) interacts with p300 similarly to p53 and other
      known oncoproteins at the CH1 amino-terminal domain as well as at a second domain
      downstream of the bromodomain which includes the CH3 region and HAT domain.
      Similarly, EBNA3C also interacts with p300 at regions which include the CH1 and
      CH3/HAT domains, suggesting that ProT(alpha) and EBNAC3C may interact in a
      complex with p300. We also show that ProT(alpha) activates transcription when
      targeted to promoters by fusion to the GAL4 DNA binding domain and that this
      activation is enhanced by the addition of an exogenous source of p300 under the
      control of a heterologous promoter. This overall activity is down-modulated in
      the presence of EBNA3C. These results further establish the interaction of
      cellular coactivator p300 with ProT(alpha) and demonstrate that the associated
      activities resulting from this interaction, which plays a role in acetylation of
      histones and coactivation, can be regulated by EBNA3C. Furthermore, this study
      establishes for the first time a transcriptional role for ProT(alpha) in
      recruitment or stabilization of coactivator p300, as well as other basal
      transcription factors, at the nucleosomes for regulation of transcription.

PMID- 11967288
TI  - Human immunodeficiency virus type 1 uses lipid raft-colocalized CD4 and chemokine
      receptors for productive entry into CD4(+) T cells.
AB  - In this report, we describe a crucial role of lipid raft-colocalized receptors in
      the entry of human immunodeficiency virus type 1 (HIV-1) into CD4(+) T cells. We
      show that biochemically isolated detergent-resistant fractions have
      characteristics of lipid rafts. Lipid raft integrity was required for productive
      HIV-1 entry as determined by (i) semiquantitative PCR analysis and (ii) single
      cycle infectivity assay using HIV-1 expressing the luciferase reporter gene and
      pseudotyped with HIV-1 HXB2 envelope or vesicular stomatitis virus envelope
      glycoprotein (VSV-G). Depletion of plasma membrane cholesterol with methyl-beta
      cyclodextrin (MbetaCD) relocalized raft-resident markers to a nonraft environment
      but did not significantly change the surface expression of HIV-1 receptors.
      MbetaCD treatment inhibited productive infection of HIV-1 by 95% as determined by
      luciferase activity in cells infected with HXB2 envelope-pseudotyped virus. In
      contrast, infection with VSV-G-pseudotyped virus, which enters the cells through
      an endocytic pathway, was not suppressed. Biochemical fractionation and confocal
      imaging of HIV-1 receptor distribution in live cells demonstrated that CD4, CCR5,
      and CXCR4 colocalized with raft-resident markers, ganglioside GM1, and
      glycosylphosphatidylinositol-anchored CD48. While confocal microscopy analysis
      revealed that HIV-1 receptors localized most likely to the same lipid
      microdomains, sucrose gradient analysis of the receptor localization showed that,
      in contrast to CD4 and CCR5, CXCR4 was associated preferentially with the nonraft
      membrane fraction. The binding of HIV-1 envelope gp120 to lipid rafts in the
      presence, but not in the absence, of cholesterol strongly supports our hypothesis
      that raft-colocalized receptors are directly involved in virus entry. Dramatic
      changes in lipid raft and HIV-1 receptor redistribution were observed upon
      binding of HIV-1 NL4-3 to PM1 T cells. Colocalization of CCR5 with GM1 and gp120
      upon engagement of CD4 and CXCR4 by HIV-1 further supports our observation that
      HIV-1 receptors localize to the same lipid rafts in PM1 T cells.

PMID- 11967289
TI  - Infectious virions produced from a human papillomavirus type 18/16 genomic DNA
      chimera.
AB  - The organotypic raft culture system has allowed the study of the differentiation
      dependent aspects of the human papillomavirus (HPV) life cycle. However, genetic
      strategies to more completely understand the HPV life cycle are limited. The
      generation of chimeric viruses has been a useful tool in other virus systems to
      analyze infection and replication. To investigate the specificity of the
      interaction of nonstructural genes of one HPV type with the structural genes of
      another HPV type, we have replaced the L2 and L1 open reading frames (ORFs) of
      HPV type 18 (HPV18) with the L2 and L1 ORFs of HPV type 16 (HPV16). The resulting
      HPV18/16 chimeric construct was introduced into primary keratinocytes, where it
      was stably maintained episomally at a range of 50 to 100 copies of HPV genomic
      DNA, similar to that typically found in HPV-infected cells in vivo. The integrity
      of the HPV18/16 genomic DNA chimera was demonstrated. Upon differentiation in
      raft cultures, late viral functions, including viral DNA amplification, capsid
      gene expression, and virion morphogenesis, occurred. Chimeric HPV18/16 virions
      were purified from the raft cultures and were capable of infecting keratinocytes
      in vitro. Additionally, infection was specifically neutralized with human HPV16
      virus-like particle (VLP)-specific antiserum and not with human HPV18 VLP
      specific antiserum. Our data demonstrate that the nonstructural genes of HPV18
      functionally interact with the structural genes of HPV16, allowing the complete
      HPV life cycle to occur. We believe that this is the first report of the
      propagation of chimeric HPV by normal life cycle pathways.

PMID- 11967290
TI  - Activation of cytomegalovirus in pig-to-primate organ xenotransplantation.
AB  - Xenotransplantation of porcine organs carries the risk of reactivation of latent
      virus in donor and recipient tissues as well as transmission of viruses between
      species. We have investigated the activation of baboon cytomegalovirus (BCMV) and
      porcine CMV (PCMV) in a pig-to-primate model of xenotransplantation. Tissues
      originating from a series of six swine-to-baboon composite thymokidney
      xenotransplants were investigated. Four immunosuppressed baboons died (survival
      range, 7 to 27 days) with the graft in situ. Increases in BCMV DNA copy numbers
      occurred in three (75%) of these baboons and was thought to be responsible for
      pneumonitis and the death of one animal. In two baboons, disseminated
      intravascular coagulation was successfully treated by graftectomy and
      discontinuation of immunosuppression. PCMV was upregulated in five of six
      xenografts (83%). PCMV infection was associated with ureteric necrosis in one
      xenograft. Although significantly increased in native tissues, low levels of BCMV
      and PCMV were also detected in tissues other than that of the native viral host
      species. The cross-species presence of CMV did not appear to cause clinical or
      histological signs of invasive disease. Thus, viral infections with clinical
      disease were restricted to tissues of the native species of each virus. Intensive
      immune suppression currently required for xenotransplantation results in a
      significant risk of reactivation of latent infections by BCMV and PCMV. It is not
      yet known whether viral DNA detected across species lines represents cellular
      microchimerism, ongoing viral infection, or uptake of free virus. The observation
      of graft injury by PCMV demonstrates that CMV will be an important pathogen in
      immunosuppressed xenograft recipients. Strategies must be developed to exclude
      CMV from porcine organ donors.

PMID- 11967291
TI  - Frequencies of virus-specific CD4(+) and CD8(+) T lymphocytes secreting gamma
      interferon after acute natural rotavirus infection in children and adults.
AB  - Human rotavirus-specific CD4(+) and CD8(+) T-cell responses in peripheral blood
      lymphocytes were studied using a flow cytometric assay that detects the
      intracellular accumulation of cytokines after short-term in vitro antigen
      stimulation. The frequencies of virus-specific T cells that secrete gamma
      interferon and interleukin-13 (IL-13) were determined in adults and children
      during the acute or convalescent phase of rotavirus-induced diarrhea, in
      asymptomatically infected adults and laboratory workers who worked with human
      stool samples containing rotavirus, and in healthy adults. Significantly higher
      frequencies of rotavirus-specific interferon gamma-secreting CD8(+) and CD4(+) T
      cells, but not IL-13-secreting T cells, were detected in symptomatically infected
      adults and exposed laboratory workers than in healthy adults and children with
      acute rotavirus diarrhea. The levels of rotavirus-specific T cells returned to
      levels found in healthy adults by 32 days after the onset of rotavirus diarrhea
      in most adult subjects. Children with rotavirus diarrhea had undetectable or very
      low levels of CD4(+) and CD8(+) T cells that secrete gamma interferon. Adult
      cytomegalovirus-seropositive individuals had frequencies of cytomegalovirus
      specific T cells that secrete gamma interferon that were approximately 20 times
      the level of rotavirus-specific T cells. This result suggests that rotavirus is a
      relatively poor inducer of circulating memory T cells that secrete gamma
      interferon. The frequencies of gamma interferon-secreting CD4(+) and CD8(+) T
      cells and the frequencies of IL-13-secreting CD4(+) T cells responding to the T
      cell superantigen staphylococcal enterotoxin B (SEB) were lower in children than
      in adults. In both adults and children, the frequencies of CD4(+) cells secreting
      gamma interferon in response to SEB were higher than the frequencies of cells
      secreting IL-13.

PMID- 11967293
TI  - Neither LAT nor open reading frame P mutations increase expression of spliced or
      intron-containing ICP0 transcripts in mouse ganglia latently infected with herpes
      simplex virus.
AB  - Latent infections by herpes simplex virus are characterized by repression of
      productive-cycle gene expression. Several hypotheses to explain this repression
      involve inhibition of expression of the immediate-early gene activator ICP0
      during latency. To address these hypotheses, we developed quantitative reverse
      transcriptase-PCR assays that detected spliced and intron-containing ICP0
      transcripts in mouse ganglia latently infected with wild-type virus. In these
      ganglia, the numbers of spliced ICP0 transcripts correlated better with the
      numbers of transcripts from the immediate-early gene encoding ICP4 than with
      those from the early gene encoding thymidine kinase. There were fewer spliced
      than intron-containing ICP0 transcripts on average, with considerable ganglion-to
      ganglion variation. We then investigated whether ICP0 expression in latently
      infected ganglia is reduced by the latency-associated transcripts (LATs) and
      whether splicing of ICP0 transcripts is inhibited by the product of open reading
      frame (ORF) P. A LAT deletion mutation which essentially eliminates expression of
      the major LATs did not appreciably increase levels of ICP0 transcripts. LAT
      deletion mutants did, however, appear to express reduced levels of intron
      containing ICP0 transcripts. ORF P mutations did not alter levels of ICP0
      transcripts in a manner consistent with inhibition of ICP0 splicing by ORF P.
      Although these results argue against antisense inhibition of ICP0 expression by
      LATs or inhibition of ICP0 splicing by ORF P, they are consistent with the
      possibilities of a block between immediate-early and early gene expression and
      regulation of spliced versus intron-containing ICP0 transcripts in latently
      infected ganglia.

PMID- 11967292
TI  - Evolution of porcine reproductive and respiratory syndrome virus during
      sequential passages in pigs.
AB  - Porcine reproductive and respiratory syndrome (PRRS) viruses are recognized as
      possessing a high degree of genetic and antigenic variability. Viral diversity
      has led to questions regarding the association of virus mutation and persistent
      infection in the host and has raised concerns vis-a-vis protective immunity, the
      ability of diagnostic assays to detect novel variants, and the possible emergence
      of virulent strains. The purpose of this study was to describe ongoing changes in
      PRRS virus during replication in pigs under experimental conditions. Animals were
      inoculated with a plaque-cloned virus derived from VR-2332, the North American
      PRRS virus prototype. Three independent lines of in vivo replication were
      maintained for 367 days by pig-to-pig passage of virus at 60-day intervals. A
      total of 315 plaque-cloned viruses were recovered from 21 pigs over the 367-day
      observation period and compared to the original plaque-cloned virus by virus
      neutralization assay, monoclonal antibody analysis, and sequencing of open
      reading frames (ORFs) 1b (replicase), 5 (major envelope protein), and 7
      (nucleocapsid) of the genome. Variants were detected by day 7 postinoculation,
      and multiple variants were present concurrently in every pig sampled over the
      observation period. Sequence analysis showed ORFs 1b and 7 to be highly
      conserved. In contrast, sequencing of ORF 5 disclosed 48 nucleotide variants
      which corresponded to 22 amino acid variants. Although no epitopic changes were
      detected under the conditions of this experiment, PRRS virus was shown to evolve
      continuously in infected pigs, with different genes of the viral genome
      undergoing various degrees of change.

PMID- 11967294
TI  - Mutations in the yellow fever virus nonstructural protein NS2A selectively block
      production of infectious particles.
AB  - Little is known about the function of flavivirus nonstructural protein NS2A. Two
      forms of NS2A are found in yellow fever virus-infected cells. Full-length NS2A
      (224 amino acids) is the product of cleavage at the NS1/2A and NS2A/2B sites.
      NS2Aalpha, a C-terminally truncated form of 190 amino acids, results from partial
      cleavage by the viral NS2B-3 serine protease at the sequence QK /T within NS2A.
      Exchange of serine for lysine at this site (QKT-->QST) blocks the production of
      both NS2Aalpha and infectious virus. The present study reveals that this defect
      is not at the level of RNA replication. Despite normal structural region
      processing, infectious particles containing genome RNA and capsid protein were
      not released from cells transfected with the mutant RNA. Nevertheless, production
      of subviral prM/M- and E-containing particles was unimpaired. The NS2A defect
      could be complemented in trans by providing NS1-2A or NS1-2Aalpha. However, trans
      complementation was not observed when the C-terminal lysine of NS1-2Aalpha was
      replaced with serine. In addition to true reversions, NS2Aalpha cleavage site
      mutations could be suppressed by two classes of second-site changes. The first
      class consisted of insertions at the NS2Aalpha cleavage site that restored its
      basic character and cleavability. A second class of suppressors occurred in the
      NS3 helicase domain, in which NS3 aspartate 343 was replaced with an uncharged
      residue (either valine, alanine, or glycine). These mutations in NS3 restored
      infectious-virus production in the absence of cleavage at the mutant NS2Aalpha
      site. Taken together, our results reveal an unexpected role for NS2A and NS3 in
      the assembly and/or release of infectious flavivirus particles.

PMID- 11967295
TI  - DNA cleavage and packaging proteins encoded by genes U(L)28, U(L)15, and U(L)33
      of herpes simplex virus type 1 form a complex in infected cells.
AB  - Previous studies have indicated that the U(L)6, U(L)15, U(L)17, U(L)28, U(L)32,
      and U(L)33 genes are required for the cleavage and packaging of herpes simplex
      viral DNA. To identify proteins that interact with the U(L)28-encoded DNA binding
      protein of herpes simplex virus type 1 (HSV-1), a previously undescribed rabbit
      polyclonal antibody directed against the U(L)28 protein fused to glutathione S
      transferase was used to immunopurify U(L)28 and the proteins with which it
      associated. It was found that the antibody specifically coimmunoprecipitated
      proteins encoded by the genes U(L)28, U(L)15, and U(L)33 from lysates of both HEp
      2 cells infected with HSV-1(F) and insect cells infected with recombinant
      baculoviruses expressing these three proteins. In reciprocal reactions,
      antibodies directed against the U(L)15- or U(L)33-encoded proteins also
      coimmunoprecipitated the U(L)28 protein. The coimmunoprecipitation of the three
      proteins from HSV-infected cells confirms earlier reports of an association
      between the U(L)28 and U(L)15 proteins and represents the first evidence of the
      involvement of the U(L)33 protein in this complex.

PMID- 11967296
TI  - HLA-Cw*04 and hepatitis C virus persistence.
AB  - In studies of acute hepatitis C virus (HCV) infection, the early host immune
      response is one of the determinants of viral persistence. The class I human
      leukocyte antigens (HLA), which present foreign antigen to cytolytic T cells, are
      integral components of this response. We hypothesized that the highly polymorphic
      HLA genes affect the outcome of an HCV infection. To test this hypothesis, we
      molecularly typed 231 persons with well-documented clearance of an HCV infection
      and 444 matched persistently infected persons. HLA-A*1101 (odds ratio [OR], 0.49;
      95% confidence interval [95% CI], 0.27 to 0.89), HLA-B*57 (OR, 0.62; 95% CI, 0.39
      to 1.00), and HLA-Cw*0102 (OR, 0.43; 95% CI, 0.21 to 0.89) were associated with
      viral clearance, whereas HLA-A*2301 (OR, 1.78; 95% CI, 1.01 to 3.11) and HLA
      Cw*04 (OR, 1.78; 95% CI, 1.21 to 2.59) were associated with viral persistence.
      HLA-Cw*04 is in strong linkage disequilibrium with HLA-B*53 and HLA-B*35, but
      only HLA-B*53 (OR, 1.70; 95% CI, 0.95 to 3.06) and the Cw*04-B*53 haplotype (OR,
      1.76; 95% CI, 0.94 to 3.26) were weakly associated with viral persistence. HLA
      B*53 has similar, but not necessarily identical, binding specificity to some HLA
      B*35 subtypes (B*35-Px group). The association with the B*35-Px group was less
      strong than with HLA-B*53 alone. The association of HLA-Cw*04 with HCV
      persistence was codominant (two copies of the gene were more strongly associated
      with persistence than one copy). However, HLA-Cw*04 was not associated with HCV
      RNA levels among the persistently infected individuals. Since Cw*04 is a ligand
      for the killer immunoglobulin-like receptors on natural killer cells, these cells
      may be involved in recovery from HCV infection. Further investigation is needed
      to understand the relationship between class I alleles and HCV clearance.

PMID- 11967297
TI  - Genetic analysis of cis regulatory elements within the 5' region of the human
      papillomavirus type 31 upstream regulatory region during different stages of the
      viral life cycle.
AB  - The function of the 5' region of the upstream regulatory region (URR) in
      regulating E6/E7 expression in cancer-associated papillomaviruses has been
      largely uncharacterized. In this study we used linker-scanning mutational
      analysis to identify potential cis regulatory elements contained within a portion
      of the 5' region of the URR that are involved in regulating transcription of the
      E6/E7 promoter at different stages of the viral life cycle. The mutational
      analysis illustrated differences in the transcriptional utilization of specific
      regions of the URR depending on the stage of the viral life cycle. This study
      identified (i) viral cis elements that regulate transcription in the presence and
      absence of any viral gene products or viral DNA replication, (ii) the role of
      host tissue differentiation in viral transcriptional regulation, and (iii) cis
      regulatory regions that are effected by induction of the protein kinase C
      pathway. Our studies have provided an extensive map of functional elements in the
      5' region (nuncleotides 7259 to 7510) of the human papillomavirus type 31 URR
      that are involved in the regulation of p99 promoter activity at different stages
      of the viral life cycle.

PMID- 11967299
TI  - Development of a vaccine against murine cytomegalovirus (MCMV), consisting of
      plasmid DNA and formalin-inactivated MCMV, that provides long-term, complete
      protection against viral replication.
AB  - We previously demonstrated that immunization of mice with plasmid DNAs (pDNAs)
      expressing the murine cytomegalovirus (MCMV) genes IE1-pp89 and M84 provided
      synergistic protection against sublethal viral challenge, while immunization with
      plasmids expressing putative virion proteins provided no or inconsistent
      protection. In this report, we sought to augment protection by increasing the
      breadth of the immune response. We identified another MCMV gene (m04 encoding
      gp34) that provided strong and consistent protection against viral replication in
      the spleen. We also found that immunization with a DNA pool containing 10 MCMV
      genes that individually were nonprotective elicited reproducible protection
      against low to intermediate doses of challenge virus. Moreover, inclusion of
      these plasmids into a mixture with gp34, pp89, and M84 DNAs provided even greater
      protection than did coimmunization with pp89 and M84. The highest level of
      protection was achieved by immunization of mice with the pool of 13 pDNAs,
      followed by formalin-inactivated MCMV (FI-MCMV). Immunization with FI-MCMV
      elicited neutralizing antibodies against salivary gland-derived MCMV, and of
      greatest importance, mice immunized with both the combined pDNA pool and FI-MCMV
      had undetectable levels of virus in the spleen and salivary glands after
      challenge. Intracellular cytokine staining of splenocytes from pDNA- and FI-MCMV
      immunized mice showed that pDNA immunization elicited high levels of pp89- and
      M83-specific CD8(+) T cells, whereas both pDNA and FI-MCMV immunizations
      generated strong CD8(+)-T-cell responses against virion-associated antigens.
      Taken together, these results show that immunization with pDNA and inactivated
      virus provides strong antibody and cell-mediated immunity against CMV infection.

PMID- 11967298
TI  - Human immunodeficiency virus type 1 neutralization measured by flow cytometric
      quantitation of single-round infection of primary human T cells.
AB  - There is currently intensive research on the design of novel human
      immunodeficiency virus type 1 (HIV-1) vaccine immunogens that can elicit potent
      neutralizing antibodies. A prerequisite for comparing and optimizing these
      strategies is the ability to precisely measure neutralizing antibody responses.
      To this end, we sought to develop an assay that directly quantifies single-round
      HIV-1 infection of peripheral blood mononuclear cells (PBMC). Initial experiments
      demonstrated that essentially all productively infected PBMC could be identified
      by flow cytometric detection of intracellular p24 antigen (p24-Ag). After
      infection of PBMC with HIV-1, p24(+) lymphocytes could be distinguished beginning
      1 day postinfection, and the majority of CD8(-) T cells were p24-Ag positive by 3
      to 4 days postinfection. To directly quantify first-round infection, we included
      a protease inhibitor in PBMC cultures. The resulting 2-day assay was highly
      sensitive and specific for the detection of HIV-1-infected PBMC. Serial dilutions
      of virus stocks demonstrated that the number of target cells infected was
      directly related to the amount of infectious virus input into the assay. In
      neutralization assays, the flow cytometric enumeration of first-round infection
      of PBMC provided quantitative data on the number of target cells infected and on
      the inactivation of infectious virus due to reaction with antibody. We also used
      this single-round assay to compare the percentage of cells expressing p24-Ag to
      the number of copies of HIV-1 gag per 100 PBMC. The precision and reproducibility
      of this assay will facilitate the measurement of HIV-1 neutralization,
      particularly incrementally improved neutralizing antibody responses generated by
      new candidate vaccines.

PMID- 11967301
TI  - A small molecule inhibits and misdirects assembly of hepatitis B virus capsids.
AB  - Hepatitis B virus (HBV) capsids play an important role in viral nucleic acid
      metabolism and other elements of the virus life cycle. Misdirection of capsid
      assembly (leading to formation of aberrant particles) may be a powerful approach
      to interfere with virus production. HBV capsids can be assembled in vitro from
      the dimeric capsid protein. We show that a small molecule, bis-ANS, binds to
      capsid protein, inhibiting assembly of normal capsids and promoting assembly of
      noncapsid polymers. Using equilibrium dialysis to investigate binding of bis-ANS
      to free capsid protein, we found that only one bis-ANS molecule binds per capsid
      protein dimer, with an association energy of -28.0 +/- 2.0 kJ/mol (-6.7 +/- 0.5
      kcal/mol). Bis-ANS inhibited in vitro capsid assembly induced by ionic strength
      as observed by light scattering and size exclusion chromatography. The binding
      energy of bis-ANS for capsid protein calculated from assembly inhibition data was
      -24.5 +/- 0.9 kJ/mol (-5.9 +/- 0.2 kcal/mol), essentially the same binding energy
      observed in studies of unassembled protein. These data indicate that capsid
      protein bound to bis-ANS did not participate in assembly; this mechanism of
      assembly inhibition is analogous to competitive or noncompetitive inhibition of
      enzymes. While assembly of normal capsids is inhibited, our data suggest that bis
      ANS leads to formation of noncapsid polymers. Evidence of aberrant polymers was
      identified by light scattering and electron microscopy. We propose that bis-ANS
      acts as a molecular "wedge" that interferes with normal capsid protein geometry
      and capsid formation; such wedges may represent a new class of antiviral agent.

PMID- 11967300
TI  - Open reading frame UL26 of human cytomegalovirus encodes a novel tegument protein
      that contains a strong transcriptional activation domain.
AB  - A selection strategy, the activator trap, was used in order to identify genes of
      human cytomegalovirus (HCMV) that encode strong transcriptional activation
      domains in mammalian cells. This approach is based on the isolation of activation
      domains from a GAL4 fusion library by means of selective plasmid replication,
      which is mediated in transfected cells by a GAL4-inducible T antigen gene. With
      this screening strategy, we were able to isolate two types of plasmids encoding
      transactivating fusion proteins from a library of random HCMV DNA inserts. One
      plasmid contained the exon 3 of the HCMV IE-1/2 gene region, which has previously
      been identified as a strong transcriptional activation domain. In the second type
      of plasmid, the open reading frame (ORF) UL26 of HCMV was fused to the GAL4 DNA
      binding domain. By quantitative RNA mapping using S1 nuclease analysis, we were
      able to classify UL26 as a strong enhancer-type activation domain with no
      apparent homology to characterized transcriptional activators. Western blot
      analysis with a specific polyclonal antibody raised against a prokaryotic UL26
      fusion protein revealed that two protein isoforms of 21 and 27 kDa are derived
      from the UL26 ORF in both infected and transfected cells. Both protein isoforms,
      which arise via alternative usage of two in-frame translational start codons,
      showed a nuclear localization and could be detected as early as 6 h after
      infection of primary human fibroblasts. By performing Western blot analysis with
      purified virions combined with fractionation experiments, we provide evidence
      that pUL26 is a novel tegument protein of HCMV that is imported during viral
      infection. Furthermore, we observed transactivation of the HCMV major immediate
      early enhancer-promoter by pUL26, whereas several early and late promoters were
      not affected. Our data suggest that pUL26 is a novel tegument protein of HCMV
      with a strong transcriptional activation domain that could play an important role
      during initiation of the viral replicative cycle.

PMID- 11967302
TI  - Ebola virus VP40 drives the formation of virus-like filamentous particles along
      with GP.
AB  - Using biochemical assays, it has been demonstrated that expression of Ebola virus
      VP40 alone in mammalian cells induced production of particles with a density
      similar to that of virions. To determine the morphological properties of these
      particles, cells expressing VP40 and the particles released from the cells were
      examined by electron microscopy. VP40 induced budding from the plasma membrane of
      filamentous particles, which differed in length but had uniform diameters of
      approximately 65 nm. When the Ebola virus glycoprotein (GP) responsible for
      receptor binding and membrane fusion was expressed in cells, we found pleomorphic
      particles budding from the plasma membrane. By contrast, when GP was coexpressed
      with VP40, GP was found on the filamentous particles induced by VP40. These
      results demonstrated the central role of VP40 in formation of the filamentous
      structure of Ebola virions and may suggest an interaction between VP40 and GP in
      morphogenesis.

PMID- 11967303
TI  - The small viral membrane-associated protein P32 is involved in bacteriophage PRD1
      DNA entry.
AB  - The lipid-containing bacteriophage PRD1 infects a variety of gram-negative cells
      by injecting its linear double-stranded DNA genome into the host cell cytoplasm,
      while the protein capsid is left outside. The virus membrane and several
      structural proteins are involved in phage DNA entry. In this work we identified a
      new infectivity protein of PRD1. Disruption of gene XXXII resulted in a mutant
      phenotype defective in phage reproduction. The absence of the protein P32 did not
      compromise the particle assembly but led to a defect in phage DNA injection. In
      P32-deficient particles the phage membrane is unable to undergo a structural
      transformation from a spherical to a tubular form. Since P32(-) particles are
      able to increase the permeability of the host cell envelope to a degree
      comparable to that found with wild-type particles, we suggest that the tail-tube
      formation is needed to eject the DNA from the phage particle rather than to reach
      the host cell interior.

PMID- 11967305
TI  - Protective cross-reactive cellular immunity to lethal A/Goose/Guangdong/1/96-like
      H5N1 influenza virus is correlated with the proportion of pulmonary CD8(+) T
      cells expressing gamma interferon.
AB  - A/Goose/Guangdong/1/96-like H5N1 influenza viruses now circulating in
      southeastern China differ genetically from the H5N1 viruses transmitted to humans
      in 1997 but were their precursors. Here we show that the currently circulating
      H9N2 influenza viruses provide chickens with cross-reactive protective immunity
      against the currently circulating H5N1 influenza viruses and that this protective
      immunity is closely related to the percentage of pulmonary CD8(+) T cells
      expressing gamma interferon (IFN-gamma). In vivo depletion of T-cell subsets
      showed that the cross-reactive immunity was mediated by T cells bearing CD8(+)
      and T-cell receptor (TCR) alpha/beta and that the Vbeta1 subset of TCR alpha/beta
      T cells had a dominant role in protective immunity. The protective immunity
      induced by infection with H9N2 virus declined with time, lasting as long as 100
      days after immunization. Shedding of A/Goose/Guangdong/1/96-like H5N1 virus by
      immunized chickens also increased with the passage of time and thus may play a
      role in the perpetuation and spread of these highly pathogenic H5N1 influenza
      viruses. Our findings indicate that pulmonary cellular immunity may be very
      important in protecting naive natural hosts against lethal influenza viruses.

PMID- 11967306
TI  - Recombinant wild-type and edmonston strain measles viruses bearing heterologous H
      proteins: role of H protein in cell fusion and host cell specificity.
AB  - Wild-type measles virus (MV) isolated from B95a cells has a restricted host cell
      specificity and hardly replicates in Vero cells, whereas the laboratory strain
      Edmonston (Ed) replicates in a variety of cell types including Vero cells. To
      investigate the role of H protein in the differential MV host cell specificity
      and cell fusion activity, H proteins of wild-type MV (IC-B) and Ed were
      coexpressed with the F protein in Vero cells. Cell-cell fusion occurred in Vero
      cells when Ed H protein, but not IC-B H protein, was expressed. To analyze the
      role of H protein in the context of viral infection, a recombinant IC-B virus
      bearing Ed H protein (IC/Ed-H) and a recombinant Ed virus bearing IC-B H protein
      (Ed/IC-H) were generated from cloned cDNAs. IC/Ed-H replicated efficiently in
      Vero cells and induced small syncytia in Vero cells, indicating that Ed H protein
      conferred replication ability in Vero cells on IC/Ed-H. On the other hand, Ed/IC
      H also replicated well in Vero cells and induced small syncytia, although
      parental Ed induced large syncytia in Vero cells. These results indicated that an
      MV protein(s) other than H protein was likely involved in determining cell fusion
      and host cell specificity of MV in the case of our recombinants. SLAM (CDw150), a
      recently identified cellular receptor for wild-type MV, was not expressed in Vero
      cells, and a monoclonal antibody against CD46, a cellular receptor for Ed, did
      not block replication or syncytium formation of Ed/IC-H in Vero cells. It is
      therefore suggested that Ed/IC-H entered Vero cells through another cellular
      receptor.

PMID- 11967304
TI  - Role of regulatory elements and the MAPK/ERK or p38 MAPK pathways for activation
      of human cytomegalovirus gene expression.
AB  - A series of recombinant viruses with either site-specific mutations or various
      deletions of the early UL4 promoter of human cytomegalovirus were used to
      determine the roles of regulatory elements and the effects of the mitogen
      activated protein kinase (MAPK) pathways. Viral gene expression was regulated by
      upstream cis-acting sites and by basic promoter elements that respond to the MAPK
      signal transduction pathways. Inhibitors of either the mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway or the p38 MAPK
      pathway affected expression equally with either wild-type or mutant early UL4
      promoters in the viral genome, indicating that the effects of the inhibitors are
      not exclusive for a single transcription factor. The minimal responsive element
      is the TATA box-containing early viral promoter.

PMID- 11967307
TI  - Mechanism of virulence attenuation of glycosaminoglycan-binding variants of
      Japanese encephalitis virus and Murray Valley encephalitis virus.
AB  - The in vivo mechanism for virulence attenuation of laboratory-derived variants of
      two flaviviruses in the Japanese encephalitis virus (JEV) serocomplex is
      described. Host cell adaptation of JEV and Murray Valley encephalitis virus (MVE)
      by serial passage in adenocarcinoma cells selected for variants characterized by
      (i) a small plaque phenotype, (ii) increased affinity to heparin-Sepharose, (iii)
      enhanced susceptibility to inhibition of infectivity by heparin, and (iv) loss of
      neuroinvasiveness in a mouse model for flaviviral encephalitis. We previously
      suggested that virulence attenuation of the host cell-adapted variants of MVE is
      a consequence of their increased dependence on cell surface glycosaminoglycans
      (GAGs) for attachment and entry (E. Lee and M. Lobigs, J. Virol. 74:8867-8875,
      2000). In support of this proposition, we find that GAG-binding variants of JEV
      and MVE were rapidly removed from the bloodstream and failed to spread from
      extraneural sites of replication into the brain. Thus, the enhanced affinity of
      the attenuated variants for GAGs ubiquitously present on cells and extracellular
      matrices most likely prevented viremia of sufficient magnitude and/or duration
      required for virus entry into the brain parenchyma. This mechanism may also
      account, in part, for the attenuation of the JEV SA14-14-2 vaccine, given the
      sensitivity of the virus to heparin inhibition. A pronounced loss of the capacity
      of the GAG-binding variants to produce disease was also noted in mice defective
      in the alpha/beta interferon response, a mouse strain shown here to be highly
      susceptible to infection with JEV serocomplex flaviviruses. Despite the close
      genetic relatedness of JEV and MVE, the variants selected for the two viruses
      were altered at different residues in the envelope (E) protein, viz., Glu(306)
      and Asp(390) for JEV and MVE, respectively. In both cases the substitutions gave
      the protein an increased net positive charge. The close spatial proximity of
      amino acids 306 and 390 in the predicted E protein structure strongly suggests
      that the two residues define a receptor-binding domain involved in virus
      attachment to sulfated proteoglycans.

PMID- 11967308
TI  - Complementation of vaccinia virus lacking the double-stranded RNA-binding protein
      gene E3L by human cytomegalovirus.
AB  - The cellular response to viral infection often includes activation of pathways
      that shut off protein synthesis and thereby inhibit viral replication. In order
      to enable efficient replication, many viruses carry genes such as the E3L gene of
      vaccinia virus that counteract these host antiviral pathways. Vaccinia virus from
      which the E3L gene has been deleted (VVDeltaE3L) is highly sensitive to
      interferon and exhibits a restricted host range, replicating very inefficiently
      in many cell types, including human fibroblast and U373MG cells. To determine
      whether human cytomegalovirus (CMV) has a mechanism for preventing translational
      shutoff, we evaluated the ability of CMV to complement the deficiencies in
      replication and protein synthesis associated with VVDeltaE3L. CMV, but not UV
      inactivated CMV, rescued VVDeltaE3L late gene expression and replication. Thus,
      complementation of the VVDeltaE3L defect appears to depend on de novo CMV gene
      expression and is not likely a result of CMV binding to the cell receptor or of a
      virion structural protein. CMV rescued VVDeltaE3L late gene expression even in
      the presence of ganciclovir, indicating that CMV late gene expression is not
      required for complementation of VVDeltaE3L. The striking decrease in overall
      translation after infection with VVDeltaE3L was prevented by prior infection with
      CMV. Finally, CMV blocked both the induction of eukaryotic initiation factor
      2alpha (eIF2alpha) phosphorylation and activation of RNase L by VVDeltaE3L. These
      results suggest that CMV has one or more immediate-early or early genes that
      ensure maintenance of a high protein synthetic capacity during infection by
      preventing activation of the PKR/eIF2alpha phosphorylation and 2-5A
      oligoadenylate synthetase/RNase L pathways.

PMID- 11967309
TI  - Expression of transcription factor AML-2 (RUNX3, CBF(alpha)-3) is induced by
      Epstein-Barr virus EBNA-2 and correlates with the B-cell activation phenotype.
AB  - To identify cell proteins regulated by the Epstein-Barr virus (EBV) transcription
      factor EBNA-2, we analyzed a cell line with conditional EBNA-2 activity by using
      microarray expression profiling. This led to the identification of two novel
      target genes induced by EBNA-2. The first of these, interleukin-16, is an
      immunomodulatory cytokine involved in the regulation of CD4 T cells. The second,
      AML-2, is a member of the Runt domain family of transcription factors. Quiescent
      B cells initially expressed AML-1 but, 48 h after virus infection, the levels of
      AML-1 decreased dramatically, whereas the amount of AML-2 protein increased.
      Analysis of a panel of B-cell lines indicated that AML-2 expression is normally
      predominant in EBV latency III, whereas AML-1 is associated with EBV latency I or
      EBV-negative cells. The AML genes are the first example of cell transcription
      factors whose expression correlates with the latency I/III phenotype.

PMID- 11967310
TI  - Mutational analysis of the v-Rel dimerization interface reveals a critical role
      for v-Rel homodimers in transformation.
AB  - The v-rel oncogene encoded by reticuloendotheliosis virus strain T is the acutely
      transforming member of the Rel/NF-kappaB family of transcription factors. In v
      Rel-transformed cells, v-Rel exists as homodimers or heterodimers with the
      endogenous Rel/NF-kappaB proteins c-Rel, NF-kappaB1, NF-kappaB2, and RelA. To
      examine the contribution of these complexes to v-Rel-mediated transformation,
      mutations were introduced into the dimerization interface of v-Rel to generate v
      Rel mutants with selective dimerization properties. Nine mutants are described in
      this study that are defective in homodimer and/or heterodimer formation with
      specific Rel/NF-kappaB family members. Viruses expressing mutants that failed to
      homodimerize but were able to form heterodimeric complexes were unable to
      transform splenic lymphocytes in vitro, indicating that the dimerization of v-Rel
      with endogenously expressed Rel/NF-kappaB proteins is not in itself sufficient
      for transformation. In addition, two partially transforming mutants were
      identified that exhibited an impaired ability to form homodimers. Sequence
      analysis of the proviral DNA from cells transformed by these mutants revealed the
      presence of multiple secondary mutations in sequences responsible for
      dimerization and DNA binding. Two of these mutations either enhanced or restored
      the ability of these proteins to bind DNA as a homodimer. Viruses expressing
      these proteins transformed cells at levels comparable to or slightly less than v
      Rel, suggesting that a threshold level of DNA binding by v-Rel homodimers is
      required for transformation.

PMID- 11967311
TI  - Molecular epidemiology of echovirus 30: temporal circulation and prevalence of
      single lineages.
AB  - Echovirus 30 (EV30) is one of the most frequently isolated EVs, causing extensive
      outbreaks of EV30 aseptic meningitis in temperate climates. EV30 is antigenically
      heterogeneous, and three major antigenic groups have been defined, although the
      basis for the antigenic differences is unknown. A reverse transcription-nested
      PCR which amplifies the 3'-terminal region of the VP1 gene directly from clinical
      samples was selected for studying EV30 molecular epidemiology, since the major
      antigenic sites in this region reflect the serotypic pattern of this virus. The
      different previous approaches to the genetic classification of EV30 were
      analyzed. A complete study of the EV30 strains was performed by analyzing the
      sequences from the 112 EV30 strains amplified in this work and the complete set
      of EV30 strains previously published. A total of 318 strains of EV30 were divided
      into two broad genotypes (I and II). This classification was supported by the
      phylogenetic trees obtained from amino acid sequences, and it correlated with the
      antigenic heterogeneity of the reference strains described in earlier studies.
      The genotypes could be further divided into subgroups, and these subgroups could
      be divided into lineages based on their nucleotide distances and levels of
      bootstrapping. On the other hand, the subgroups and lineages did not result in
      the same correlation between amino acid and nucleotide differentiation. The
      molecular epidemiology of EV30 can be compared to influenza virus epidemiology,
      where prevailing lineages displace the less established lineages on the basis of
      immune escape. This pattern of evolution is clearly different from that of other
      enteroviruses. A single lineage at a time appears to be circulating worldwide.
      This behavior may be related to the epidemic activity of EV30.

PMID- 11967312
TI  - cis-Acting elements important for retroviral RNA packaging specificity.
AB  - Spleen necrosis virus (SNV) proteins can package RNA from distantly related
      murine leukemia virus (MLV), whereas MLV proteins cannot package SNV RNA
      efficiently. We used this nonreciprocal recognition to investigate regions of
      packaging signals that influence viral RNA encapsidation specificity. Although
      the MLV and SNV packaging signals (Psi and E, respectively) do not contain
      significant sequence homology, they both contain a pair of hairpins. This hairpin
      pair was previously proposed to be the core element in MLV Psi. In the present
      study, MLV-based vectors were generated to contain chimeric SNV/MLV packaging
      signals in which the hairpins were replaced with the heterologous counterpart.
      The interactions between these chimeras and MLV or SNV proteins were examined by
      virus replication and RNA analyses. SNV proteins recognized all of the chimeras,
      indicating that these chimeras were functional. We found that replacing the
      hairpin pair did not drastically alter the ability of MLV proteins to package
      these chimeras. These results indicate that, despite the important role of the
      hairpin pair in RNA packaging, it is not the major motif responsible for the
      ability of MLV proteins to discriminate between the MLV and SNV packaging
      signals. To determine the role of sequences flanking the hairpins in RNA
      packaging specificity, vectors with swapped flanking regions were generated and
      evaluated. SNV proteins packaged all of these chimeras efficiently. In contrast,
      MLV proteins strongly favored chimeras with the MLV 5'-flanking regions. These
      data indicated that MLV Gag recognizes multiple elements in the viral packaging
      signal, including the hairpin structure and flanking regions.

PMID- 11967313
TI  - Herpes simplex virus tegument protein VP22 contains overlapping domains for
      cytoplasmic localization, microtubule interaction, and chromatin binding.
AB  - We have previously shown that the 301-amino-acid herpes simplex virus tegument
      protein VP22 exhibits a range of subcellular localization patterns when expressed
      in isolation from other virus proteins. By using live-cell analysis of cells
      expressing green fluorescent protein (GFP)-tagged VP22 we have shown that when
      VP22 is first expressed in the cell it localizes to the cytoplasm, where, when
      present at high enough concentrations, it can assemble onto microtubules, causing
      them to bundle and become highly stabilized. In addition we have shown that when
      a cell expressing VP22 enters mitosis, the cytoplasmic population of VP22
      translocates to the nucleus, where it efficiently binds mitotic chromatin. Here
      we have investigated the specific regions of the VP22 open reading frame required
      for these properties. Using GFP-VP22 as our starting molecule, we have
      constructed a range of N- and C-terminal truncations and analyzed their
      localization patterns in live cells. We show that the C-terminal 242 residues of
      VP22 are sufficient to induce microtubule bundling. Within this subregion, the C
      terminal 89 residues contain a signal for cytoplasmic localization of the
      protein, while a larger region comprising the C-terminal 128 residues of the VP22
      protein is required for mitotic chromatin binding. Furthermore, a central 100
      residue domain of VP22 maintains the ability to bind microtubules without
      inducing bundling, suggesting that additional regions flanking this microtubule
      binding domain may be required to alter the microtubule network. Hence, the
      signals involved in dictating the complex localization patterns of VP22 are
      present in overlapping regions of the protein.

PMID- 11967314
TI  - Comprehensive screening for human immunodeficiency virus type 1 subtype-specific
      CD8 cytotoxic T lymphocytes and definition of degenerate epitopes restricted by
      HLA-A0207 and -C(W)0304 alleles.
AB  - For this report, the rapid identification and characterization of human
      immunodeficiency virus type 1 (HIV-1)-derived broadly cross-subtype-reactive CD8
      cytotoxic T lymphocyte (CTL) epitopes were performed. Using a gamma interferon
      (IFN-gamma) Elispot assay-based approach and a panel of recombinant vaccinia
      viruses expressing gag, env, pol, and nef genes representing the seven most
      predominant subtypes and one circulating recombinant form of HIV-1, the subtype
      specificity and cross-subtype reactivity of a CD8 response were directly measured
      from circulating peripheral blood mononuclear cells (PBMC). Enhanced sensitivity
      of detection of CD8 responses from cryopreserved PBMC was achieved using
      autologous vaccinia virus-infected B-lymphoblastoid cell lines as supplemental
      antigen-presenting cells. Of eleven subjects studied, six exhibited broadly cross
      subtype-reactive CD8-mediated IFN-gamma production (at least seven of eight
      subtypes recognized) to at least one major gene product from HIV-1. Screening of
      subjects showing broadly cross-subtype-specific responses in the vaccinia virus
      based enzyme-linked immunospot (Elispot) assay using a panel of overlapping
      peptides resulted in the identification of cross-subtype responses down to the 20
      mer peptide level in less than 3 days. Three subjects showed broad cross-subtype
      reactivity in both the IFN-gamma Elispot assay and the standard chromium release
      cytotoxicity assay. Fine mapping and HLA restriction analysis of the response
      from three subjects demonstrated that this technique can be used to define
      epitopes restricted by HLA-A, -B, and -C alleles. In addition, the ability of all
      three epitopes to be processed from multiple subtypes of their parent proteins
      and presented in the context of HLA class I molecules following de novo synthesis
      is shown. While all three minimal epitopes mapped here had previously been
      defined as HIV-1 epitopes, two are shown to have novel HLA restriction alleles
      and therefore exhibit degenerate HLA binding capacity. These findings provide
      biological validation of HLA supertypes in HIV-1 CTL recognition and support
      earlier studies of cross-subtype CTL responses during HIV-1 infection.

PMID- 11967315
TI  - Genetic evidence for a structural interaction between the carboxy termini of the
      membrane and nucleocapsid proteins of mouse hepatitis virus.
AB  - The coronavirus membrane (M) protein is the most abundant virion protein and the
      key component in viral assembly and morphogenesis. The M protein of mouse
      hepatitis virus (MHV) is an integral membrane protein with a short ectodomain,
      three transmembrane segments, and a large carboxy-terminal endodomain facing the
      interior of the viral envelope. The carboxy terminus of MHV M has previously been
      shown to be extremely sensitive to mutation, both in a virus-like particle
      expression system and in the intact virion. We have constructed a mutant,
      M(Delta)2, containing a two-amino-acid truncation of the M protein that was
      previously thought to be lethal. This mutant was isolated by means of targeted
      RNA recombination with a powerful host range-based selection allowed by the
      interspecies chimeric virus fMHV (MHV containing the ectodomain of the feline
      infectious peritonitis virus S protein). Analysis of multiple second-site
      revertants of the M(Delta)2 mutant has revealed changes in regions of both the M
      protein and the nucleocapsid (N) protein that can compensate for the loss of the
      last two residues of the M protein. Our data thus provide the first genetic
      evidence for a structural interaction between the carboxy termini of the M and N
      proteins of MHV. In addition, this work demonstrates the efficacy of targeted
      recombination with fMHV for the systematic genetic analysis of coronavirus
      structural protein interactions.

PMID- 11967316
TI  - Characterization of interactions between RTA and the promoter of polyadenylated
      nuclear RNA in Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8.
AB  - RTA (replication and transcription activator; also referred to as ORF50, Lyta,
      and ART), an immediate-early gene product of Kaposi's sarcoma-associated
      herpesvirus (KSHV)/human herpesvirus 8, disrupts latency and drives lytic
      replication. RTA activates the expression of polyadenylated nuclear (PAN) RNA
      (also known as T1.1 or nut-1) of KSHV. This novel noncoding PAN RNA is the most
      abundant lytic transcript of KSHV; therefore, studying PAN RNA expression serves
      as a model system for understanding how RTA transactivates target genes during
      lytic replication. The RTA-responsive element of the PAN promoter (pPAN RRE) was
      previously identified, and our data suggested direct binding of full-length RTA
      to the pPAN RRE. Here, we present a detailed analysis of specific interactions
      between RTA and the PAN promoter. We expressed and purified the DNA-binding
      domain of RTA (Rdbd) to near homogeneity and measured its affinity for the pPAN
      RRE. In electrophoretic mobility shift assays (EMSAs), the dissociation constant
      (K(d)) of Rdbd on the pPAN RRE was determined to be approximately 8 x 10(-9) M,
      suggesting a strong interaction between RTA and DNA. The specificity of RTA
      binding to the PAN promoter was confirmed with supershift assays. The Rdbd
      binding sequences on the PAN promoter were mapped within a 16-bp region of the
      pPAN RRE by methylation interference assays. However, the minimal DNA sequence
      for Rdbd binding requires an additional 7 bp on both sides of the area mapped by
      interference assays, suggesting that non-sequence-specific as well as sequence
      specific interactions between RTA and DNA contribute to high-affinity binding. To
      better understand the molecular interactions between RTA and the PAN promoter, an
      extensive mutagenesis study on the pPAN RRE was carried out by using EMSAs and
      reporter assays. These analyses revealed base pairs critical for both Rdbd
      binding in vitro and RTA transactivation in vivo of the PAN promoter. The results
      from methylation interference, deletion analysis, and mutagenesis using EMSAs and
      reporter assays were closely correlated and support the hypothesis that RTA
      activates PAN RNA expression through direct binding to DNA.

PMID- 11967317
TI  - Human TATA binding protein inhibits human papillomavirus type 11 DNA replication
      by antagonizing E1-E2 protein complex formation on the viral origin of
      replication.
AB  - The human papillomavirus (HPV) protein E2 possesses dual roles in the viral life
      cycle. By interacting directly with host transcription factors in basal
      keratinocytes, E2 promotes viral transcription. As keratinocyte differentiation
      progresses, E2 associates with the viral helicase, E1, to activate vegetative
      viral DNA replication. How E2's major role switches from transcription to
      replication during keratinocyte differentiation is not understood, but the
      presence of a TATA site near the viral origin of replication led us to
      hypothesize that TATA-binding protein (TBP) could affect HPV replication. Here we
      show that the C-terminal domain of TBP (TBPc) is a potent inhibitor of E2
      stimulated HPV DNA replication in vitro (50% inhibitory concentration = 0.56 nM).
      Increasing the E1 concentration could not overcome TBPc inhibition in replication
      assays, indicating that TBPc is a noncompetitive inhibitor of E1 binding. While
      direct E2-TBPc association could be demonstrated, this interaction could not
      fully account for the mechanism of TBPc-mediated inhibition of viral replication.
      Because E2 supports sequence-specific binding of E1 to the viral ori, we proposed
      that TBPc antagonizes E1-ori association indirectly through inhibition of E2-DNA
      binding. Indeed, TBPc potently antagonized E2 binding to DNA in the absence (K(i)
      = 0.5 +/- 0.1 nM) and presence (K(i) = 0.6 +/- 0.3 nM) of E1. Since E2 and TBPc
      cannot be coadjacent on viral sequences, direct DNA-binding competition between
      TBPc and E2 was responsible for replication inhibition. Given the ability of TBPc
      to inhibit HPV DNA replication in vitro and data indicating that TBPc antagonized
      E2-ori association, we propose that transcription factors regulate HPV DNA
      replication as well as viral transcription.

PMID- 11967318
TI  - Pestivirus internal ribosome entry site (IRES) structure and function: elements
      in the 5' untranslated region important for IRES function.
AB  - The importance of certain structural features of the 5' untranslated region of
      classical swine fever virus (CSFV) RNA for the function of the internal ribosome
      entry site (IRES) was investigated by mutagenesis followed by in vitro
      transcription and translation. Deletions made from the 5' end of the CSFV genome
      sequence showed that the IRES boundary was close to nucleotide 65: thus, the IRES
      includes the whole of domain II but no sequences upstream of this domain.
      Deletions which invaded domain II even to a small extent reduced activity to
      about 20% that of the full-length structure, and this 20% residual activity
      persisted with more extensive deletions until the whole of domain II had been
      removed and the deletions invaded the pseudoknot, whereupon IRES activity fell to
      zero. The importance of both stems of the pseudoknot was verified by making
      mutations in both sides of each stem; this severely reduced IRES activity, but
      the compensating mutations which restored base pairing caused almost full IRES
      function to be regained. The importance of the length of the loop linking the two
      stems of the pseudoknot was demonstrated by the finding that a reduction in
      length from the wild-type AUAAAAUU to AUU almost completely abrogated IRES
      activity. Random A-->U substitutions in the wild-type sequence showed that IRES
      activity was fairly proportional to the number of A residues retained in this
      pseudoknot loop, with a preference for clustered neighboring A residues rather
      than dispersed As. Finally, it was found that the sequence of the highly
      conserved domain IIIa loop is, rather surprisingly, not important for the
      maintenance of full IRES activity, although amputation of the entire domain IIIa
      stem and loop was highly debilitating. These results are interpreted in the light
      of recent models, derived from cryo-electron microscopy, of the interaction of
      the closely related hepatitis C virus IRES with 40S ribosomal subunits.

PMID- 11967320
TI  - Human cytomegalovirus gene products US2 and US11 differ in their ability to
      attack major histocompatibility class I heavy chains in dendritic cells.
AB  - Human cytomegalovirus (HCMV) encodes several proteins that inhibit major
      histocompatibility complex (MHC) class I-dependent antigen presentation. The HCMV
      products US2 and US11 are each sufficient for causing the dislocation of human
      and murine MHC class I heavy chains from the lumen of the endoplasmic reticulum
      to the cytosol, where the heavy chains are readily degraded. The apparent
      redundancy of US2 and US11 has been probed predominantly in cultured cell lines,
      where differences in their specificities were shown for murine and human MHC
      class I locus products. Here, we expressed US11 and US2 via adenovirus vectors
      and show that US11 exhibits a superior ability to degrade MHC class I molecules
      in primary human dendritic cells. MHC class II complexes are unaffected by US2-
      and US11-mediated attack. We suggest that multiple HCMV-encoded immunoevasions
      have evolved complementary functions in response to diverse host cell types and
      tissues.

PMID- 11967321
TI  - Strength of envelope protein interaction modulates cytopathicity of measles
      virus.
AB  - To understand the molecular determinants of measles virus (MV) cytopathicity, we
      have characterized mutant viruses exhibiting a more-extensive cell-to-cell fusion
      while maintaining efficient replication to high titers. A virus which is modified
      by the addition of an 8-amino-acid Flag epitope tag at the cytoplasmic tail of
      its H (for MV hemagglutinin) envelope glycoprotein replicates efficiently, has an
      increased cytopathicity, possesses a greater infectivity per particle, and has an
      altered protein composition compared with that of unmodified MV. The mutant
      phenotype is not specifically linked to the epitope sequence, since an
      alternatively added HA (for influenza virus-derived hemagglutinin) epitope tag
      caused similar effects. We demonstrate that both epitope tags weaken the
      interaction between the H and fusion (F) glycoproteins in virus-infected cells.
      This reduction in strength of H/F interaction is independent of the presence of
      the viral matrix (M) protein. Viruses with this less stable complex are more
      sensitive to neutralization by a soluble octameric form of the CD46 receptor,
      consistent with their increased fusogenicity. Similar analyses of glycoproteins
      derived from MV strains with reduced cytopathicities confirm that the strength of
      H and F glycoprotein interaction is a modulator of viral fusogenicity.

PMID- 11967319
TI  - Inhibition of histone deacetylases induces bovine leukemia virus expression in
      vitro and in vivo.
AB  - Packaging into nucleosomes results in a global transcriptional repression as a
      consequence of exclusion of sequence-specific factors. This inhibition can be
      relieved by using inhibitors of histone deacetylases, acetylation being a major
      characteristic of transcriptionally active chromatin. Paradoxically, the
      expression of only approximately 2% of the total cellular genes is modulated by
      histone hyperacetylation. To unravel the potential role of this transcriptional
      control on BLV expression, we tested the effect of two highly specific inhibitors
      of deacetylases, trichostatin A (TSA) and trapoxin (TPX). Our results demonstrate
      that treatment with TSA efficiently enhanced long terminal repeat-directed gene
      expression of integrated reporter constructs in heterologous D17 stable cell
      lines. To further examine the biological relevance of these observations made in
      vitro, we analyzed ex vivo-isolated peripheral blood mononuclear cells (PBMCs)
      from bovine leukemia virus (BLV)-infected sheep. TSA deacetylase inhibitor
      induced a drastic increase in viral expression at levels comparable to those
      induced by treatment with phorbol-12-myristate 13-acetate and ionomycin, the most
      efficient activators of BLV expression known to date. TSA acted directly on BLV
      infected B lymphocytes to increase viral expression and does not seem to require
      T-cell cooperation. Inhibition of deacetylation after treatment with TSA or TPX
      also significantly increased viral expression in PBMCs from cattle, the natural
      host for BLV. Together, our results show that BLV gene expression is, like that
      of a very small fraction of cellular genes, also regulated by deacetylation.

PMID- 11967322
TI  - Abnormal priming of CD4(+) T cells by dendritic cells expressing hepatitis C
      virus core and E1 proteins.
AB  - Patients infected with hepatitis C virus (HCV) have an impaired response against
      HCV antigens while keeping immune competence for other antigens. We hypothesized
      that expression of HCV proteins in infected dendritic cells (DC) might impair
      their antigen-presenting function, leading to a defective anti-HCV T-cell
      immunity. To test this hypothesis, DC from normal donors were transduced with an
      adenovirus coding for HCV core and E1 proteins and these cells (DC-CE1) were used
      to stimulate T lymphocytes. DC-CE1 were poor stimulators of allogeneic reactions
      and of autologous primary and secondary proliferative responses. Autologous T
      cells stimulated with DC-CE1 exhibited a pattern of incomplete activation
      characterized by enhanced CD25 expression but reduced interleukin 2 production.
      The same pattern of incomplete lymphocyte activation was observed in CD4(+) T
      cells responding to HCV core in patients with chronic HCV infection. However,
      CD4(+) response to HCV core was normal in patients who cleared HCV after alpha
      interferon therapy. Moreover, a normal CD4(+) response to tetanus toxoid was
      found in both chronic HCV carriers and patients who had eliminated the infection.
      Our results suggest that expression of HCV structural antigens in infected DC
      disturbs their antigen-presenting function, leading to incomplete activation of
      anti-HCV-specific T cells and chronicity of infection. However, presentation of
      unrelated antigens by noninfected DC would allow normal T-cell immunity to other
      pathogens.

PMID- 11967323
TI  - Primary immune responses by cord blood CD4(+) T cells and NK cells inhibit
      Epstein-Barr virus B-cell transformation in vitro.
AB  - Epstein-Barr virus (EBV) transformation of B cells from fetal cord blood in vitro
      varies depending on the individual sample. When a single preparation of EBV was
      simultaneously used to transform fetal cord blood samples from six different
      individuals, the virus transformation titer varied from less than zero to
      10(5.9). We show that this variation in EBV transformation is associated with a
      marked primary immune response in cord blood samples predominately involving
      CD4(+) T cells and CD16(+) CD56(+) NK cells. After virus challenge both CD4(+) T
      cells and NK cells in fetal cord blood cultures expressed the lymphocyte
      activation marker CD69. The cytotoxic response against autologous EBV-infected
      lymphoblastoid cell line (LCL) targets correlated with the number of CD16(+)
      CD69(+) cells and was inversely correlated with the virus transformation titer.
      Although NK activity was detected in fresh cord blood and increased following
      activation by the virus, killing of autologous LCLs was detected only following
      activation by exposure to the virus. Both activated CD4(+) T cells and CD16(+) NK
      cells were independently able to kill autologous LCLs. Both interleukin-2 and
      gamma interferon were produced by CD4(+) T cells after virus challenge. The titer
      of EBV was lower when purified B cells were used than when whole cord blood was
      used. Addition of monocytes restored the virus titer, while addition of resting T
      cells or EBV-activated CD4(+) T-cell blasts reduced the virus titer. We conclude
      that there are primary NK-cell and Th1-type CD4(+) T-cell responses to EBV in
      fetal cord blood that limit the expansion of EBV-infected cells and in some cases
      eliminate virus infection in vitro.

PMID- 11967325
TI  - Death of CD4(+) T-cell lines caused by human immunodeficiency virus type 1 does
      not depend on caspases or apoptosis.
AB  - A critical aspect of AIDS pathogenesis that remains unclear is the mechanism by
      which human immunodeficiency virus type 1 (HIV-1) induces death in CD4(+) T
      lymphocytes. A better understanding of the death process occurring in infected
      cells may provide valuable insight into the viral component responsible for
      cytopathicity. This would aid the design of preventive treatments against the
      rapid decline of CD4(+) T cells that results in AIDS. Previously, apoptotic cell
      death has been reported in HIV-1 infections in cultured T cells, and it has been
      suggested that this could affect both infected and uninfected cells. To evaluate
      the mechanism of this effect, we have studied HIV-1-induced cell death
      extensively by infecting several T-cell lines and assessing the level of
      apoptosis by using various biochemical and flow cytometric assays. Contrary to
      the prevailing view that apoptosis plays a prominent role in HIV-1-mediated T
      cell death, we found that Jurkat and H9 cells dying from HIV-1 infection fail to
      exhibit the collective hallmarks of apoptosis. Among the parameters investigated,
      Annexin V display, caspase activity and cleavage of caspase substrates, TUNEL
      (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling)
      signal, and APO2.7 display were detected at low to negligible levels. Neither
      peptide caspase inhibitors nor the antiapoptotic proteins Bcl-x(L) or v-FLIP
      could prevent cell death in HIV-1-infected cultures. Furthermore, Jurkat cell
      lines deficient in RIP, caspase-8, or FADD were as susceptible as wild-type
      Jurkat cells to HIV-1 cytopathicity. These results suggest that the primary mode
      of cytopathicity by laboratory-adapted molecular clones of HIV-1 in cultured cell
      lines is not via apoptosis. Rather, cell death occurs most likely via a necrotic
      or lytic form of death independent of caspase activation in directly infected
      cells.

PMID- 11967324
TI  - Cytopathic killing of peripheral blood CD4(+) T lymphocytes by human
      immunodeficiency virus type 1 appears necrotic rather than apoptotic and does not
      require env.
AB  - An important unresolved issue of AIDS pathogenesis is the mechanism of human
      immunodeficiency virus (HIV)-induced CD4(+) T-lymphocyte destruction. We show
      here that HIV type 1 (HIV-1) exerts a profound cytopathic effect upon peripheral
      blood CD4(+) T lymphocytes that resembles necrosis rather than apoptosis.
      Necrotic cytopathology was found with both laboratory-adapted strains and primary
      isolates of HIV-1. We carefully investigated the role of env, which has been
      previously implicated in HIV cytopathicity. HIV-1 stocks with equivalent
      infectivity were prepared from constructs with either an intact or mutated env
      coding region and pseudotyped with the glycoprotein of vesicular stomatitis virus
      (VSV-G) so that the HIV envelope was not rate-limiting for infection. Infected
      Jurkat T cells died whether or not env was intact; however, the expression of env
      accelerated death significantly. The accelerated death was blocked by protease
      inhibitors, indicating that it was due to reinfection by newly produced virus in
      env(+) cultures. Accordingly, we found no disparity in kinetics in CD4(lo) Jurkat
      cells. In highly infected peripheral blood T cells, profound necrosis occurred
      equivalently with both env(+) and env(-) stocks of HIV-1. We also found that HIV
      1 cytopathicity was undiminished by the absence of nef. However, viral stocks
      made by complementation or packaging of HIV-1 genomes with the natural protein
      coding sequences replaced by the green fluorescent protein were highly infectious
      but not cytopathic. Thus, env can accelerate cell death chiefly as an entry
      function, but one or more viral functions other than env or nef is essential for
      necrosis of CD4(+) T cells induced by HIV-1.

PMID- 11967326
TI  - Positive and negative modulation of human immunodeficiency virus type 1 Rev
      function by cis and trans regulators of viral RNA splicing.
AB  - Expression of the entire complement of human immunodeficiency virus type 1 (HIV
      1) viral proteins depends on the competing activities of viral RNA splicing and
      export into the cytoplasm by Rev. To investigate the possibility that modulation
      of viral RNA metabolism may alter Rev function, we analyzed the impact of
      multiple SR proteins on both processes. While overexpression of several of the SR
      factors altered splicing of HIV-1 env mRNA, they had disparate effects on Rev
      function that varied with the cell line used. Subsequent examination of exon
      splicing enhancer (ESE) and/or silencer (ESS) deletions suggests that the effects
      of the SR proteins on Rev function are not mediated through interaction with
      these elements. However, analysis of the deletions did indicate that the ESE
      and/or ESS does have significant effects on Rev function, with deletion of the
      ESS augmenting the magnitude of the response to Rev and deletion of the ESE
      significantly reducing it. In situ hybridization and reverse transcription-PCR
      indicated that the loss of Rev response upon deletion of the ESE was due to a
      failure of Rev to induce transport of the unspliced RNA into the cytoplasm.
      Together, the data indicate that cellular splicing factors and viral regulatory
      elements can have significant stimulatory and inhibitory effects on Rev function,
      raising the possibility that cells can be rendered permissive or nonpermissive
      for virus replication by modulation of splicing activities.

PMID- 11967327
TI  - Mutational analysis of simian virus 40 T-antigen primosome activities in viral
      DNA replication.
AB  - The recruitment of DNA polymerase alpha-primase (pol-prim) is a crucial step in
      the establishment of a functional replication complex in eukaryotic cells, but
      the mechanism of pol-prim loading and the composition of the eukaryotic primosome
      are poorly understood. In the model system for simian virus 40 (SV40) DNA
      replication in vitro, synthesis of RNA primers at the origin of replication
      requires only the viral tumor (T) antigen, replication protein A (RPA), pol-prim,
      and topoisomerase I. On RPA-coated single-stranded DNA (ssDNA), T antigen alone
      mediates priming by pol-prim, constituting a relatively simple primosome. T
      antigen activities proposed to participate in its primosome function include DNA
      helicase and protein-protein interactions with RPA and pol-prim. To test the role
      of these activities of T antigen in mediating priming by pol-prim, three
      replication-defective T antigens with mutations in the ATPase or helicase domain
      have been characterized. All three mutant proteins interacted physically and
      functionally with RPA and pol-prim and bound ssDNA, and two of them displayed
      some helicase activity. However, only one of these, 5030, mediated primer
      synthesis and elongation by pol-prim on RPA-coated ssDNA. The results suggest
      that a novel activity, present in 5030 T antigen and absent in the other two
      mutants, is required for T-antigen primosome function.

PMID- 11967328
TI  - Temporary blockade of the tumor necrosis factor receptor signaling pathway
      impedes the spread of scrapie to the brain.
AB  - Although the transmissible spongiform encephalopathies (TSEs) are
      neurodegenerative diseases, their agents usually replicate and accumulate in
      lymphoid tissues long before infection spreads to the central nervous system
      (CNS). Studies of a mouse scrapie model have shown that mature follicular
      dendritic cells (FDCs), which express the host prion protein (PrP(c)), are
      critical for replication of infection in lymphoid tissues. In the absence of
      mature FDCs, the spread of infection to the CNS is significantly impaired. Tumor
      necrosis factor alpha (TNF-alpha) secretion by lymphocytes is important for
      maintaining FDC networks, and signaling is mediated through TNF receptor 1 (TNFR
      1) expressed on FDCs and/or their precursors. A treatment that blocks TNFR
      signaling leads to the temporary dedifferentiation of mature FDCs, raising the
      hypothesis that a similar treatment would significantly delay the peripheral
      pathogenesis of scrapie. Here, specific neutralization of the TNFR signaling
      pathway was achieved through treatment with a fusion protein consisting of two
      soluble human TNFR (huTNFR) (p80) domains linked to the Fc portion of human
      immunoglobulin G1 (huTNFR:Fc). A single treatment of mice with huTNFR:Fc before
      or shortly after intraperitoneal injection with the ME7 scrapie strain
      significantly delayed the onset of disease in the CNS and reduced the early
      accumulation of disease-specific PrP in the spleen. These effects coincided with
      a temporary dedifferentiation of mature FDCs within 5 days of huTNFR:Fc
      treatment. We conclude that treatments that specifically inhibit the TNFR
      signaling pathway may present an opportunity for early intervention in
      peripherally transmitted TSEs.

PMID- 11967329
TI  - New World arenavirus clade C, but not clade A and B viruses, utilizes alpha
      dystroglycan as its major receptor.
AB  - Alpha-dystroglycan (alpha-DG) has been identified as a major receptor for
      lymphocytic choriomeningitis virus (LCMV) and Lassa virus, two Old World
      arenaviruses. The situation with New World arenaviruses is less clear: previous
      studies demonstrated that Oliveros virus also exhibited high-affinity binding to
      alpha-DG but that Guanarito virus did not. To extend these initial studies,
      several additional Old and New World arenaviruses were screened for entry into
      mouse embryonic stem cells possessing or lacking alpha-DG. In addition,
      representative viruses were further analyzed for direct binding to alpha-DG by
      means of a virus overlay protein blot assay technique. These studies indicate
      that Old World arenaviruses use alpha-DG as a major receptor, whereas, of the New
      World arenaviruses, only clade C viruses (i.e., Oliveros and Latino viruses) use
      alpha-DG as a major receptor. New World clade A and B arenaviruses, which include
      the highly pathogenic Machupo, Guanarito, Junin, and Sabia viruses, appear to use
      a different receptor or coreceptor for binding. Previous studies with LCMV have
      suggested the need for a small aliphatic amino acid at LCMV GP1 glycoprotein
      amino acid position 260 to allow high-affinity binding to alpha-DG. As reported
      herein, this requirement appears to be broadly applicable to the arenaviruses as
      determined by more extensive analysis of alpha-DG receptor usage and GP1
      sequences of Old and New World arenaviruses. In addition, GP1 amino acid position
      259 also appears to be important, since all arenaviruses showing high-affinity
      alpha-DG binding possess a bulky aromatic amino acid (tyrosine or phenylalanine)
      at this position.

PMID- 11967332
TI  - Relationship between vaccinia virus intracellular cores, early mRNAs, and DNA
      replication sites.
AB  - Virus assembly, a late event in the life cycle of vaccinia virus (VV), is
      preceded by a number of steps that all occur in the cytoplasm of the infected
      host cell: virion entry, delivery of the viral core into the cytoplasm, and
      transcription from these cores of early mRNAs, followed by the process of DNA
      replication. In the present study the quantitative and structural relationships
      between these distinct steps of VV morphogenesis were investigated. We show that
      viral RNA and DNA synthesis increases linearly with increasing amounts of
      incoming cores. Moreover, at multiplicities of infection that result in 10 to 40
      cores per cell, an approximately 1:1 ratio between cores and sites of DNA
      replication exists, suggesting that each core is infectious. We have shown
      previously that VV early mRNAs collect in distinct granular structures that
      recruit components of the host cell translation machinery. Strikingly, these
      structures appeared to form some distance away from intracellular cores (M.
      Mallardo, S. Schleich, and J. Krijnse Locker, Mol. Biol. Cell 12:3875-3891,
      2001). In the present study the intracellular locations of the sites of early
      mRNA accumulation and those of the subsequent process of DNA replication were
      compared. We show that these are distinct structures that have different
      intracellular locations. Finally, we study the fate of the parental DNA after
      core uncoating. By electron microscopy, cores were found close to membranes of
      the endoplasmic reticulum (ER) and the parental DNA, once it had left the core,
      appeared to associate preferentially with the cytosolic side of those membranes.
      Since we have previously shown that the process of DNA replication occurs in an
      ER-enclosed cytosolic "subcompartment" (N. Tolonen, L. Doglio, S. Schleich, and
      J. Krijnse Locker, Mol. Biol. Cell 12:2031-2046, 2001), the present data suggest
      that the parental DNA is released into the cytosol and associates with the same
      membranes where DNA replication is subsequently initiated. The combined data are
      discussed with respect to the cytosolic organization of VV morphogenesis.

PMID- 11967330
TI  - Retrieval of human cytomegalovirus glycoprotein B from cell surface is not
      required for virus envelopment in astrocytoma cells.
AB  - Human cytomegalovirus (HCMV) is a prototypic member of the betaherpesvirus
      family. The HCMV virion is composed of a large DNA genome encapsidated within a
      nucleocapsid, which is wrapped within an inner proteinaceous tegument and an
      outer lipid envelope containing viral glycoproteins. Although genome
      encapsidation clearly occurs in the nucleus, the subsequent steps in the virion
      assembly process are unclear. HCMV glycoprotein B (gB) is a major component of
      the virion envelope that plays a critical role in virus entry and is essential
      for the production of infectious virus progeny. The aim of our present study was
      to identify the secretory compartment to which HCMV gB was localized and to
      investigate the role of endocytosis in mediating gB localization and HCMV
      biogenesis. We show that HCMV gB is localized to the trans-Golgi network (TGN) in
      HCMV-infected cells and that gB contains all of the trafficking information
      necessary for TGN localization. Endocytosis of gB was shown to play a role in
      mediating TGN localization of gB and in targeting of the protein to the site of
      virus envelopment. However, inhibition of endocytosis with a dominant-negative
      dynamin I molecule did not affect the production of infectious virus. These
      observations indicate that, although endocytosis is involved in the trafficking
      of gB to the site of glycoprotein accumulation in the TGN, endocytosis of gB is
      not required for the production of infectious HCMV.

PMID- 11967331
TI  - Caveolar endocytosis of simian virus 40 is followed by brefeldin A-sensitive
      transport to the endoplasmic reticulum, where the virus disassembles.
AB  - Simian virus 40 (SV40) enters cells by atypical endocytosis mediated by caveolae
      that transports the virus to the endoplasmic reticulum (ER) instead of to the
      endosomal-lysosomal compartment, which is the usual destination for viruses and
      other cargo that enter by endocytosis. We show here that SV4O is transported to
      the ER via an intermediate compartment that contains beta-COP, which is best
      known as a component of the COPI coatamer complexes that are required for the
      retrograde retrieval pathway from the Golgi to the ER. Additionally, transport of
      SV40 to the ER, as well as infection, is sensitive to brefeldin A. This drug acts
      by specifically inhibiting the ARF1 GTPase, which is known to regulate assembly
      of COPI coat complexes on Golgi cisternae. Moreover, some beta-COP colocalizes
      with intracellular caveolin-1, which was previously shown to be present on a new
      organelle (termed the caveosome) that is an intermediate in the transport of SV40
      to the ER (L. Pelkmans, J. Kartenbeck, and A. Helenius, Nat. Cell Biol. 3:473
      483, 2001). We also show that the internal SV40 capsid proteins VP2 and VP3
      become accessible to immunostaining starting at about 5 h. Most of that
      immunostaining overlays the ER, with some appearing outside of the ER. In
      contrast, immunostaining with anti-SV40 antisera remains confined to the ER.

PMID- 11967334
TI  - Nuclear IE2 structures are related to viral DNA replication sites during
      baculovirus infection.
AB  - The ie2 gene of Autographa californica multicapsid nuclear polyhedrosis virus is
      1 of the 10 baculovirus genes that have been identified as factors involved in
      viral DNA replication. IE2 is detectable in the nucleus as one of the major early
      expressed proteins and exhibits a dynamic localization pattern during the
      infection cycle (D. Murges, I. Quadt, J. Schroer, and D. Knebel-Morsdorf, Exp.
      Cell Res. 264:219-232, 2001). Here, we investigated whether IE2 localized to
      regions of viral DNA replication. After viral DNA was labeled with
      bromodeoxyuridine (BrdU), confocal imaging indicated that defined IE2 domains
      colocalized with viral DNA replication centers as soon as viral DNA replication
      was detectable. In addition, a subpopulation of IE2 structures colocalized with
      two further virus-encoded replication factors, late expression factor 3 (LEF-3)
      and the DNA binding protein (DBP). While DBP and LEF-3 structures always
      colocalized and enlarged simultaneously with viral DNA replication sites, only
      those IE2 structures that colocalized with replication sites also colocalized
      with DBP. Replication and transcription of DNA viruses in association with
      promyelocytic leukemia protein (PML) oncogenic domains have been observed. By
      confocal imaging we demonstrated that the human PML colocalized with IE2. Triple
      staining revealed PML/IE2 domains in the vicinity of viral DNA replication
      centers, while IE2 alone colocalized with early replication sites, demonstrating
      that PML structures do not form common domains with viral DNA replication
      centers. Thus, we conclude that IE2 colocalizes alternately with PML and the
      sites of viral DNA replication. Small ubiquitin-like modifier SUMO-1 has been
      implicated in the nuclear distribution of PML. Similar to what was found for
      mammalian cells, small ubiquitin-like modifiers were recruited to PML domains in
      infected insect cells, which suggests that IE2 and PML colocalize in conserved
      cellular domains. In summary, our results support a model for IE2 as part of
      various functional sites in the nucleus that are connected with viral DNA
      replication.

PMID- 11967333
TI  - Sites and determinants of early cleavages in the proteolytic processing pathway
      of reovirus surface protein sigma3.
AB  - Entry of mammalian reovirus virions into target cells requires proteolytic
      processing of surface protein sigma3. In the virion, sigma3 mostly covers the
      membrane-penetration protein mu1, appearing to keep it in an inactive form and to
      prevent it from interacting with the cellular membrane until the proper time in
      infection. The molecular mechanism by which sigma3 maintains mu1 in this inactive
      state and the structural changes that accompany sigma3 processing and mu1
      activation, however, are not well understood. In this study we characterized the
      early steps in sigma3 processing and determined their effects on mu1 function and
      particle infectivity. We identified two regions of high protease sensitivity,
      "hypersensitive" regions located at residues 208 to 214 and 238 to 244, within
      which all proteases tested selectively cleaved sigma3 as an early step in
      processing. Further processing of sigma3 was required for infection, consistent
      with the fact that the fragments resulting from these early cleavages remained
      bound to the particles. Reovirus type 1 Lang (T1L), type 3 Dearing (T3D), and T1L
      x T3D reassortant virions differed in the sites of early sigma3 cleavage, with
      T1L sigma3 being cleaved mainly at residues 238 to 244 and T3D sigma3 being
      cleaved mainly at residues 208 to 214. These virions also differed in the rates
      at which the early cleavages occurred, with cleavage of T1L sigma3 occurring
      faster than cleavage of T3D sigma3. Analyses using chimeric and site-directed
      mutants of recombinant sigma3 identified carboxy-proximal residues 344, 347, and
      353 as the primary determinants of these strain differences. The spatial
      relationships between these more carboxy-proximal residues and the hypersensitive
      regions were discerned from the sigma3 crystal structure. The results indicate
      that proteolytic processing of sigma3 during reovirus disassembly is a multistep
      pathway with a number of molecular determinants.

PMID- 11967336
TI  - Rapid directional translocations in virus replication.
AB  - By viewing virus development in real time, the experiments reported here reveal
      novel processes--rapid directional translocations--that are likely to be
      important elements of virus replication. Herpes simplex virus type 1 (HSV-1) was
      labeled by the fusion of the green fluorescent protein to a structural protein of
      its tegument (VP11/12), the product of gene UL46. Infection of cultured cells
      with this recombinant virus (GHSV-UL46) produced fluorescent particles that were
      distributed throughout the cytoplasm with concentrations in the perinuclear
      region; they were absent from the nucleus. Viewing infected cells in real time by
      means of video microscopy produced a novel dynamic picture of virus development.
      Most strikingly, some of the fluorescent particles exhibited extremely rapid
      directional translocations at velocities as great as 5 microm/s. The trajectories
      and destinations of these particles suggest that the rapid directional
      translocations serve at least three functions: the rapid transport of viral
      components to and between cytoplasmic processing stations, the delivery of
      materials for functions specific to the perinuclear region, and the conveyance of
      maturing virus particles to the plasma membrane. These rapid directional
      translocations are novel elements of virus assembly that are likely to be
      critical for efficient replication.

PMID- 11967335
TI  - Transcriptional downregulation of ORF50/Rta by methotrexate inhibits the switch
      of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 from latency to
      lytic replication.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a cellular dihydrofolate
      reductase (DHFR) homologue. Methotrexate (MTX), a potent anti-inflammatory agent,
      inhibits cellular DHFR activity. We investigated the effect of noncytotoxic doses
      of MTX on latency and lytic KSHV replication in two KSHV-infected primary
      effusion lymphoma cell lines (BC-3 and BC-1) and in MTX-resistant BC-3 cells (MTX
      R-BC-3 cells). Treatment with MTX completely prevented tetradecanoyl phorbol
      acetate-induced viral DNA replication and strongly decreased viral lytic
      transcript levels, even in MTX-resistant cells. However, the same treatment had
      no effect on transcription of cellular genes and KSHV latent genes. One of the
      lytic transcripts inhibited by MTX, ORF50/Rta (open reading frame), is an
      immediate-early gene encoding a replication-transcription activator required for
      expression of other viral lytic genes. Therefore, transcription of genes
      downstream of ORF50/Rta was inhibited, including those encoding the viral G
      protein-coupled receptor (GPCR), viral interleukin-6, and K12/kaposin, which have
      been shown to be transforming in vitro and oncogenic in mice. Resistance to MTX
      has been documented in cultured cells and also in patients treated with this
      drug. However, MTX showed an inhibitory activity even in MTX-R-BC-3 cells. Two
      currently available antiherpesvirus drugs, cidofovir and foscarnet, had no effect
      on the transcription of these viral oncogenes and ORF50/Rta. MTX is the first
      example of a compound shown to downregulate the expression of ORF50/Rta and
      therefore prevent viral transforming gene transcription. Given that the
      expression of these genes may be important for tumor development, MTX could play
      a role in the future management of KSHV-associated malignancies.

PMID- 11967337
TI  - Interaction of the coronavirus nucleoprotein with nucleolar antigens and the host
      cell.
AB  - Coronavirus nucleoproteins (N proteins) localize to the cytoplasm and the
      nucleolus, a subnuclear structure, in both virus-infected primary cells and in
      cells transfected with plasmids that express N protein. The nucleolus is the site
      of ribosome biogenesis and sequesters cell cycle regulatory complexes. Two of the
      major components of the nucleolus are fibrillarin and nucleolin. These proteins
      are involved in nucleolar assembly and ribosome biogenesis and act as chaperones
      for the import of proteins into the nucleolus. We have found that fibrillarin is
      reorganized in primary cells infected with the avian coronavirus infectious
      bronchitis virus (IBV) and in continuous cell lines that express either IBV or
      mouse hepatitis virus N protein. Both N protein and a fibrillarin-green
      fluorescent protein fusion protein colocalized to the perinuclear region and the
      nucleolus. Pull-down assays demonstrated that IBV N protein interacted with
      nucleolin and therefore provided a possible explanation as to how coronavirus N
      proteins localize to the nucleolus. Nucleoli, and proteins that localize to the
      nucleolus, have been implicated in cell growth-cell cycle regulation. Comparison
      of cells expressing IBV N protein with controls indicated that cells expressing N
      protein had delayed cellular growth. This result could not to be attributed to
      apoptosis. Morphological analysis of these cells indicated that cytokinesis was
      disrupted, an observation subsequently found in primary cells infected with IBV.
      Coronaviruses might therefore delay the cell cycle in interphase, where maximum
      translation of viral mRNAs can occur.

PMID- 11967338
TI  - Blockade of interferon induction and action by the E3L double-stranded RNA
      binding proteins of vaccinia virus.
AB  - The vaccinia virus E3L gene encodes two double-stranded RNA binding proteins that
      promote viral growth and pathogenesis through suppression of innate immunity. To
      explore how E3L enables vaccinia virus to evade the interferon system, cells and
      mice deficient in the principal interferon-regulated antiviral enzymes, PKR and
      RNase L, were infected with wild-type vaccinia virus and strains of vaccinia
      virus from which E3L had been deleted (E3L-deleted strains). While wild-type
      virus was unaffected by RNase L and PKR, virus lacking E3L replicated only in the
      deficient cells. Nevertheless, E3L-deleted virus failed to replicate to high
      titers or to cause significant morbidity or mortality in triply deficient mice
      lacking RNase L, PKR, and Mx1. To investigate the underlying cause, we determined
      the effect of E3L on interferon regulatory factor 3 (IRF3), a transcription
      factor required for viral induction of subtypes of type I interferons. Results
      showed that IRF3 activation and interferon-beta induction occurred after
      infections with E3L-deleted virus but not with wild-type virus. These findings
      demonstrate that E3L plays an essential role in the pathogenesis of vaccinia
      virus by blocking the interferon system at multiple levels. Furthermore, our
      results indicate the existence of an interferon-mediated antipoxvirus pathway
      that operates independently of PKR, Mx1, or the 2-5A/RNase L system.

PMID- 11967339
TI  - Persistent infection of human thymic epithelial cells by coxsackievirus B4.
AB  - Persistent replication of coxsackievirus B4 (CVB4) E2 (diabetogenic) and CVB4 JBV
      (nondiabetogenic) strains in thymic epithelial cell (TEC)-enriched cultures
      (>or=95%) was proved by detection of positive- and negative-strand viral RNA by
      reverse transcription-PCR in extracted RNA from cell cultures, VP1 capsid protein
      detection by immunofluorescence (IF) staining, and release of infectious
      particles up to 30 days after infection without obvious cytolysis. By double-IF
      staining, cytokeratin-containing cells were shown to be susceptible to CVB4. The
      persistence of CVB4 was associated with a significantly increased rate of TEC
      proliferation (up to 70%) after 20 days of culture and a significantly increased
      chronic production of immunoreactive interleukin-6 (IL-6), leukemia inhibitory
      factor, and granulocyte-macrophage colony-stimulating factor in supernatant after
      3 days of culture. The CVB4 replication and the release of cytokines were not
      restricted to the CVB4 E2 diabetogenic strain and did not depend on the genetic
      background of the host; however, TEC were more responsive to CVB4 E2 than CVB4
      JBV as far as the production of cytokines.

PMID- 11967340
TI  - Association of the caveola vesicular system with cellular entry by filoviruses.
AB  - The filoviruses Ebola Zaire virus and Marburg virus are believed to infect target
      cells through endocytic vesicles, but the details of this pathway are unknown. We
      used a pseudotyping strategy to investigate the cell biology of filovirus entry.
      We observed that specific inhibitors of the caveola system, including cholesterol
      sequestering drugs and phorbol esters, inhibited the entry of filovirus
      pseudotypes into human cells. We also measured slower cell entry kinetics for
      both filovirus pseudotypes than for pseudotypes of vesicular stomatitis virus
      (VSV), which has been recognized to exploit the clathrin-mediated entry pathway.
      Finally, visualization by immunofluorescence and confocal microscopy revealed
      that the filovirus pseudotypes colocalized with the caveola protein marker
      caveolin-1 but that VSV pseudotypes did not. Collectively, these results provide
      evidence suggesting that filoviruses use caveolae to gain entry into cells.

PMID- 11967342
TI  - Activation of NF-kappaB by R5 and X4 human immunodeficiency virus type 1 induces
      macrophage inflammatory protein 1alpha and tumor necrosis factor alpha in
      macrophages.
AB  - NF-kappaB is a transcriptional activator that often regulates inflammatory
      responses. We demonstrate that human immunodeficiency virus type 1 activates
      nuclear localization of NF-kappaB in macrophages in a manner dependent upon virus
      strain but independent of virus replication. Through the use of an inhibitor, NF
      kappaB activation was found to be responsible for the cytokine and chemokine
      induction that we recently reported.

PMID- 11967341
TI  - The liver is a major organ for clearing simian immunodeficiency virus in rhesus
      monkeys.
AB  - Infection with human or simian immunodeficiency virus (SIV) is characterized by
      the rapid turnover of both viral particles and productively infected cells. It
      has recently been reported that the clearance of SIV in vivo is exceedingly fast,
      with half-lives on the order of minutes. The underlying mechanism or site
      responsible for this rapid clearance, however, remains unknown. To investigate
      this issue, we chose to infuse infectious SIVmac239 grown from autologous
      peripheral blood mononuclear cells that were radioactively labeled by
      [(35)S]methionine and [(35)S]cysteine. This approach eliminates from the viral
      membrane alloantigens that may have a significant impact on viral clearance. In
      addition, this approach also permits identification of the sites of viral
      clearance by measuring the radioactive intensity, even if degradation of SIV RNA
      occurs in tissues. We now report that the half-life of infused SIV in blood is
      extremely close to estimates from a previous study, in which unlabeled SIV grown
      in a heterologous cell line was used. The allogeneic effect due to the presence
      of human antigens on the surfaces of virions may, therefore, play a minimal role
      in the high rate of virion clearance. Moreover, close to 30% of infused
      radioactivity was found in the liver and measureable amounts were detected in the
      lungs (5.4%), lymph nodes (3.0%), and spleen (0.4%). The detection of a
      significant proportion of infused virus in the liver suggests that viral
      clearance from circulation is mediated by a common, nonspecific mechanism, such
      as the phagocytic functions of the reticuloendothelial system. The rapid
      clearance and degradation of exogenously infused virions may pose a major
      obstacle for gene therapy with viral vectors, unless strategies to overcome the
      rapid in vivo elimination of these particles are developed.

PMID- 11967344
TI  - Expression of a membrane-anchored glycoprotein, the influenza virus
      hemagglutinin, by dicistronic replicons derived from the poliovirus genome.
AB  - Mono- and dicistronic poliovirus replicons were constructed to express the
      influenza virus hemagglutinin, retaining its signal peptide and transmembrane
      region. Picornavirus genomes do not normally encode glycoproteins, and only the
      dicistronic replicon, in which the foreign and poliovirus sequences were
      separated by the encephalomyocarditis virus internal ribosomal entry site,
      replicated and expressed glycosylated hemagglutinin.

PMID- 11967343
TI  - Molecular evolution of human immunodeficiency virus env in humans and monkeys:
      similar patterns occur during natural disease progression or rapid virus passage.
AB  - Neonatal rhesus macaque 95-3 was inoculated with nonpassaged simian-human
      immunodeficiency virus strain SHIV-vpu(+), which encodes env of the laboratory
      adapted human immunodeficiency virus (HIV) strain IIIB and is considered
      nonpathogenic. CD4(+) T-cell counts dropped to <200 cells/microl within 4.6
      years, and monkey 95-3 died with opportunistic infections 5.9 years
      postinoculation. Transfer of blood from 95-3 to two naive adult macaques resulted
      in high peak viral loads and rapid, persistent T-cell depletion. Progeny virus
      evolved in 95-3 despite high SHIV-vpu(+) neutralizing antibody titers and still
      used CXCR4 but, in contrast to parental SHIV-vpu(+), productively infected
      macrophages and resisted neutralization. Sequence analysis revealed three new
      potential glycosylation sites in gp120; another two were lost. Strikingly similar
      mutations were detected in a laboratory worker who progressed to AIDS after
      accidental HIV-IIIB infection (T. Beaumont et al., J. Virol. 75:2246-2252, 2001),
      thus supporting the SHIV-vpu(+)/rhesus macaque system as a relevant model.
      Similar mutations were also described after rapid passage of chimeric viruses
      encoding IIIB env in rhesus and pig-tailed macaques (M. Cayabyab et al., J.
      Virol. 73:976-984, 1999; Z. Q. Liu et al., Virology 260:295-307, 1999; S. V.
      Narayan et al., Virology 256:54-63, 1999; R. Raghavan et al., Brain Pathol. 7:851
      861, 1997; E. B. Stephens et al., Virology 231:313-321, 1997). Thus, HIV-IIIB env
      evolved similarly in three different species; this selection occurred in
      chronically infected individuals during disease progression as well as after
      rapid virus passage. We postulate that evolutionary pressure led to the outgrowth
      of more aggressive viral variants in all three species.

PMID- 11967346
TI  - The problem with material safety data sheets.

PMID- 11967348
TI  - Work-related injuries and occupational health and safety factors in smaller
      enterprises--a prospective study.
AB  - The aim of this study was to determine whether any of the health, environmental
      and safety (HES) factors registered by visiting small mechanical enterprises in
      Norway at the start of the study could predict the risk of occupational injuries
      in subsequent years. Twelve HES factors, including injury awareness, programme
      for action, employee participation, training and use of personal safety devices,
      were registered. A questionnaire was completed by interviewing the employer and
      observing production. Two variables based on observation of the use of safety
      equipment were significantly correlated with occupational injuries. There is
      potential for prevention in smaller enterprises by increasing the use of personal
      protection devices and safety equipment on machines. Frequent inspection with
      feedback to the workers is probably the most effective means of attaining the
      desired result of reducing injuries.

PMID- 11967345
TI  - RNA-binding activity of the rotavirus phosphoprotein NSP5 includes affinity for
      double-stranded RNA.
AB  - Phosphoprotein NSP5 is a component of replication intermediates that catalyze the
      synthesis of the segmented double-stranded RNA (dsRNA) rotavirus genome. To study
      the role of the protein in viral replication, His-tagged NSP5 was expressed in
      bacteria and purified by affinity chromatography. In vitro phosphorylation assays
      showed that NSP5 alone contains minimal autokinase activity but undergoes
      hyperphosphorylation when combined with the NTPase and helix-destabilizing
      protein NSP2. Hence, NSP2 mediates the hyperphosphorylation of NSP5 in the
      absence of other viral or cellular proteins. RNA-binding assays demonstrated that
      NSP5 has unique nonspecific RNA-binding activity, recognizing single-stranded RNA
      and dsRNA with similar affinities. The possible functions of the RNA-binding
      activities of NSP5 are to cooperate with NSP2 in the destabilization of RNA
      secondary structures and in the packaging of RNA and/or to prevent the interferon
      induced dsRNA-dependent activation of the protein kinase PKR.

PMID- 11967350
TI  - Occupational health in the European Union.
AB  - Despite extensive legislation in the European Union, employees remain exposed to
      occupational risks and there is still a significant burden of work-related ill
      health. The trend for more people to work in service industries rather than
      manufacturing has resulted in a change in the nature of risk and pattern of
      occupational illness. Worker access to occupational health services ranges from
      15 to 96% and depends on the country in which employees live and the type of
      operation in which they work. The increasing number of small enterprises provides
      a particular challenge when trying to provide occupational health support to the
      European Union's 158.4 million workers. European law alone is not sufficient to
      improve the health of those at work and further action is needed at state,
      employer and professional level. New initiatives seek to improve the health of
      the Union's workforce, including a drive for better compliance with new law by
      every member state. Governments are working with key stakeholders through
      partnering strategies to develop innovative approaches for better access to
      quality occupational health services. Furthermore, targets for reduction in
      occupational ill-health have been identified. Where country laws do not mandate
      the provision of occupational health services, employers need to see the benefit
      of providing occupational health support. Finally, the medical profession is
      making procedures for self-regulation more rigorous and professional bodies are
      actively engaged in issuing professional standards and guidelines. Ultimately,
      the individual practitioner is responsible for ensuring that he or she develops
      and maintains the necessary knowledge and skills to provide competent services.

PMID- 11967349
TI  - Surveillance for work-related hearing loss in the UK: OSSA and OPRA 1997-2000.
AB  - Surveillance data on occupational audiological disorders have been collected by
      the Occupational Surveillance Scheme for Audiological Physicians (OSSA) since
      October 1997 and by the Occupational Physicians Reporting Activity (OPRA) from
      January 1996. During the 3 years ending in September 2000, a total of 1620 new
      cases were received from consultant audiological physicians; 988 new cases were
      estimated from reports by occupational physicians in the period from October 1997
      to September 2000. The annual incidence of occupational noise-induced hearing
      loss (NIHL) was 1.94 and 1.23 per 100 000 workers for the OSSA and OPRA schemes,
      respectively. The median age at diagnosis with NIHL was 59 years in OSSA reports
      and 50 years in OPRA; nearly all cases were seen in men (95.6 and 92.5% male
      cases for OSSA and OPRA, respectively). High incidence rates based on OSSA
      reports were seen in foundry labourers (64.0 per 100 000 employed), coal gas and
      coke oven furnace workers (54.6), workers in transport and communication (43.1),
      metal workers (31.3), and members of the armed forces (28.3). Data from
      occupational physicians point to high rates in sawyers and woodworking
      machinists, metal furnace workers, coach and carriage builders, maintenance
      fitters, and engineering labourers. Among workers aged < or =45 years, those in
      manufacturing and the armed forces were prominent. The long latency of
      occupational hearing loss makes surveillance difficult, but consistent patterns
      in occupational risk suggest targets for preventive efforts.

PMID- 11967351
TI  - Does military service damage females? An analysis of medical discharge data in
      the British armed forces.
AB  - There is anecdotal and some scientific evidence that females in military service
      experience an excess of work-related injuries, compared with males. To
      investigate this more fully, we analysed data collected routinely by the Defence
      Analytical Services Agency on medical discharges in male and female personnel in
      the British armed forces. We found that for all disease and injury categories of
      medical discharge there is a statistically significant excess in females; this
      disparity is particularly marked for discharges on account of injury [relative
      risk (RR) = 1.65, 95% confidence interval (95% CI) = 1.30-2.10] and
      musculoskeletal disease (RR = 3.34, 95% CI = 2.75-4.06). Royal Navy females are
      eight times more likely (RR = 7.92, 95% CI = 3.03-20.66) and Army females seven
      times more likely (RR = 6.53, 95% CI = 2.60-16.42) than Royal Air Force females
      to be medically discharged on account of injury. Over the period 1993-1996, there
      was a statistically significant increase in the rate of medical discharge for
      both musculoskeletal disease and injury in female personnel in the British armed
      forces. During the period 1996-2000, a marked gender differential was maintained,
      but the rate of increase in females reached a plateau. We concur with previous
      investigators that mixed-sex training imposes particular ergonomic stresses on
      females and that it is a major risk factor for overuse injury. We discuss other
      possible explanations for the marked gender differential in medical discharge
      rates in the military. Some changes to training programmes are now being
      introduced to correct this health inequality, but further interventions are
      needed. Modifications to training programmes must be audited systematically and
      candidate interventions tested through randomized controlled trials.

PMID- 11967352
TI  - Frequent musculoskeletal symptoms and reduced health-related quality of life
      among industrial workers.
AB  - The high percentage of musculoskeletal symptoms (MSS) found in studies of general
      populations and various occupational groups underlines the need to distinguish
      between severely and mildly affected individuals. To investigate associations
      between MSS and quality of life, we examined the frequency of MSS on a five-point
      scale, health-related quality of life (SF-36) and sickness absence among 5654
      workers in the aluminium industry. High frequencies of MSS from all body parts
      were related to lower scores on the SF-36 and increased sickness absence. This
      relationship was strongest for MSS from the lower back. Workers who reported low
      back MSS 'very often' had a mean role--physical score equivalent to that of the
      15th percentile of the general population. These results show that workers who
      reported MSS often or very often were severely affected, and this scale can
      therefore be used to distinguish individuals at high risk for reduced health
      related quality of life and sickness absence.

PMID- 11967354
TI  - Occupational electrocutions in Jefferson County, Alabama.
AB  - Few studies have presented the general epidemiology of electrocution deaths using
      local medical examiner data. Data were obtained from coroner/medical examiner's
      files for electrocution deaths occurring between 1981 and 1998. All 27
      occupational electrocutions were among men; 92.6% were white and 7.4% were black,
      with a mean age of 33.1 years. The rates of high- and low-voltage electrocution
      were similar. Low-voltage deaths showed a seasonal pattern, with the largest
      numbers in July, August and October. Deaths occurred most frequently among
      electricians and electrical helpers. The level of detail available from medical
      examiner records permits more complete evaluation of injury patterns than is
      possible using death certificate data; however, even more detailed studies,
      exploring worker activity at the time of injury, education, experience and
      training, are needed.

PMID- 11967353
TI  - Occupational voice disorders due to workplace exposure to irritants--a review of
      the literature.
AB  - The medical literature contains relatively few examples of reports of voice
      disorders that could be attributed to chemical exposure at work. General medical
      conditions such as gastro-oesophageal reflux and the use of medication such as
      inhaled steroids are well-recognized causes of laryngitis, but the occupational
      causes are less well documented. This paper describes the results of a literature
      review looking at the reporting of cases of occupationally acquired voice
      disorders due to exposure to irritants in the workplace.

PMID- 11967357
TI  - Effects of molecular crowding by saccharides on alpha-chymotrypsin dimerization.
AB  - Given the importance of protein complexes as therapeutic targets, it is necessary
      to understand the physical chemistry of these interactions under the crowded
      conditions that exist in cells. We have used sedimentation equilibrium to
      quantify the enhancement of the reversible homodimerization of alpha-chymotrypsin
      by high concentrations of the osmolytes glucose, sucrose, and raffinose. In an
      attempt to rationalize the osmolyte-mediated stabilization of the alpha
      chymotrypsin homodimer, we have used models based on binding interactions
      (transfer-free energy analysis) and steric interactions (excluded volume theory)
      to predict the stabilization. Although transfer-free energy analysis predicts
      reasonably well the relatively small stabilization observed for complex formation
      between cytochrome c and cytochrome c peroxidase, as well as that between bobtail
      quail lysozyme and a monoclonal Fab fragment, it underestimates the sugar
      mediated stabilization of the alpha-chymotrypsin dimer. Although predictions
      based on excluded volume theory overestimate the stabilization, it would seem
      that a major determinant in the observed stabilization of the alpha-chymotrypsin
      homodimer is the thermodynamic nonideality arising from molecular crowding by the
      three small sugars.

PMID- 11967358
TI  - Distance dependence and salt sensitivity of pairwise, coulombic interactions in a
      protein.
AB  - Histidine pK(a) values were measured in charge-reversal (K78E, K97E, K127E, and
      K97E/K127E) and charge-neutralization (E10A, E101A, and R35A) mutants of
      staphylococcal nuclease (SNase) by (1)H-NMR spectroscopy. Energies of interaction
      between pairs of charges (DeltaG(ij)) were obtained from the shifts in pK(a)
      values relative to wild-type values. The data describe the distance dependence
      and salt sensitivity of pairwise coulombic interactions. Calculations with a
      continuum electrostatics method captured the experimental DeltaG(ij) when static
      structures were used and when the protein interior was treated empirically with a
      dielectric constant of 20. The DeltaG(ij) when r(ij) < or = 10 A were exaggerated
      slightly in the calculations. Coulomb's law with a dielectric constant near 80
      and a Debye-Huckel term to account for screening by the ionic strength reproduced
      the salt sensitivity and distance dependence of DeltaG(ij) as well as the
      structure-based method. In their interactions with each other, surface charges
      behave as if immersed in water; the Debye length describes realistically the
      distance where interactions become negligible at a given ionic strength. On
      average, charges separated by distances (r(ij)) approximately 5 A interacted with
      DeltaG(ij) approximately 0.6 kcal/mole in 0.01 M KCl, but DeltaG(ij) decayed to <
      or =0.10 kcal/mole when r(ij) = 20 A. In 0.10 M KCl, DeltaG(ij) approximately
      0.10 kcal/mole when r(ij) = 10 A. In 1.5 M KCl, only short-range interactions
      with r(ij) < or = 5 A persisted. Although at physiological ionic strengths the
      interactions between charges separated by more than 10 A are extremely weak, in
      situations where charge imbalance exists many weak interactions can cumulatively
      produce substantial effects.

PMID- 11967359
TI  - Direct comparison of binding equilibrium, thermodynamic, and rate constants
      determined by surface- and solution-based biophysical methods.
AB  - The binding interactions of small molecules with carbonic anhydrase II were used
      as model systems to compare the reaction constants determined from surface- and
      solution-based biophysical methods. Interaction data were collected for two
      arylsulfonamide compounds, 4-carboxybenzenesulfonamide (CBS) and 5-dimethyl-amino
      1-naphthalene-sulfonamide (DNSA), binding to the enzyme using surface plasmon
      resonance, isothermal titration calorimetry, and stopped-flow fluorescence. We
      demonstrate that when the surface plasmon resonance biosensor experiments are
      performed with care, the equilibrium, thermodynamic, and kinetic constants
      determined from this surface-based technique match those acquired in solution.
      These results validate the use of biosensor technology to collect reliable data
      on small molecules binding to immobilized macromolecular targets. Binding
      kinetics were shown to provide more detailed information about complex formation
      than equilibrium constants alone. For example, although carbonic anhydrase II
      bound DNSA with twofold higher affinity than CBS, kinetic analysis revealed that
      CBS had a fourfold slower dissociation rate. Analysis of the binding and
      transition state thermodynamics also revealed significant differences in the
      enthalpy and entropy of complex formation. The lack of labeling requirements,
      high information content, and high throughput of surface plasmon resonance
      biosensors will make this technology an important tool for characterizing the
      interactions of small molecules with enzymes and receptors.

PMID- 11967361
TI  - Exploring protein aggregation and self-propagation using lattice models: phase
      diagram and kinetics.
AB  - Many seemingly unrelated neurodegenerative disorders, such as amyloid and prion
      diseases, are associated with propagating fibrils whose structures are
      dramatically different from the native states of the corresponding monomers. This
      observation, along with the experimental demonstration that any protein can
      aggregate to form either fibrils or amorphous structures (inclusion bodies) under
      appropriate external conditions, suggest that there must be general principles
      that govern aggregation mechanisms. To probe generic aspects of prion-like
      behavior we use the model of Harrison, Chan, Prusiner, and Cohen. In this model,
      aggregation of a structure, that is conformationally distinct from the native
      state of the monomer, occurs by three parallel routes. Kinetic partitioning,
      which leads to parallel assembly pathways, occurs early in the aggregation
      process. In all pathways transient unfolding precedes polymerization and self
      propagation. Chain polymerization is consistent with templated assembly, with the
      dimer being the minimal nucleus. The kinetic effciency of R(n-1) + G --> R(n) (R
      is the aggregation prone state and G is either U, the unfolded state, or N, the
      native state of the monomer) is increased when polymerization occurs in the
      presence of a "seed" (a dimer). These results support the seeded nucleated
      polymerization model of fibril formation in amyloid peptides. To probe generic
      aspects of aggregation in two-state proteins, we use lattice models with side
      chains. The phase diagram in the (T,C) plane (T is the temperature and C is the
      polypeptide concentration) reveals a bewildering array of "phases" or structures.
      Explicit computations for dimers show that there are at least six phases
      including ordered structures and amorphous aggregates. In the ordered region of
      the phase diagram there are three distinct structures. We find ordered dimers
      (OD) in which each monomer is in the folded state and the interaction between the
      monomers occurs via a well-defined interface. In the domain-swapped structures a
      certain fraction of intrachain contacts are replaced by interchain contacts. In
      the parallel dimers the interface is stabilized by favorable intermolecular
      hydrophobic interactions. The kinetics of folding to OD shows that aggregation
      proceeds directly from U in a dynamically cooperative manner without populating
      partially structured intermediates. These results support the experimental
      observation that ordered aggregation in the two-state folders U1A and CI2 takes
      place from U. The contrasting aggregation processes in the two models suggest
      that there are several distinct mechanisms for polymerization that depend not
      only on the polypeptide sequence but also on external conditions (such as C, T,
      pH, and salt concentration).

PMID- 11967360
TI  - Timing and structural consideration for the processing of mitochondrial matrix
      space proteins by the mitochondrial processing peptidase (MPP).
AB  - Most mitochondrial matrix space proteins are synthesized as a precursor protein,
      and the N-terminal extension of amino acids that served as the leader sequence is
      removed after import by the action of a metalloprotease called mitochondrial
      processing peptidase (MPP). The crystal structure of MPP has been solved very
      recently, and it has been shown that synthetic leader peptides bind with MPP in
      an extended conformation. However, it is not known how MPP recognizes hundreds of
      leader peptides with different primary and secondary structures or when during
      import the leader is removed. Here we took advantage of the fact that the
      structure of the leader from rat liver aldehyde dehydrogenase has been determined
      by 2D-NMR to possess two helical portions separated by a three amino acid (RGP)
      linker. When the linker was deleted, the leader formed one long continuous helix
      that can target a protein to the matrix space but is not removed by the action of
      MPP. Repeats of two and three leaders were fused to the precursor protein to
      determine the stage of import at which processing occurs, if MPP could function
      as an endo peptidase, and if it would process if the cleavage site was part of a
      helix. Native or linker deleted constructs were used. Import into isolated yeast
      mitochondria or processing with recombinantly expressed MPP was performed. It was
      concluded that processing did not occur as the precursor was just entering the
      matrix space, but most likely coincided with the folding of the protein. Further,
      finding that hydrolysis could not take place if the processing site was part of a
      stable helix is consistent with the crystal structure of MPP. Lastly, it was
      found that MPP could function at sites as far as 108 residues from the N terminus
      of the precursor protein, but its ability to process decreases exponentially as
      the distance increases.

PMID- 11967362
TI  - Oligomerization of acidic fibroblast growth factor is not a prerequisite for its
      cell proliferation activity.
AB  - Oligomerization of fibroblast growth factors (FGFs) induced on binding to heparin
      or heparan sulfate proteoglycan is considered to be crucial for receptor
      activation and initiation of biological responses. To gain insight into the
      mechanism of activation of the receptor by FGFs, in the present study we
      investigate the effect(s) of interaction of a heparin analog, sucrose octasulfate
      (SOS), on the structure, stability, and biological activities of a recombinant
      acidic FGF from Notophthalmus viridescens (nFGF-1). SOS is found to bind to nFGF
      1 and significantly increase the thermodynamic stability of the protein. Using a
      variety of techniques such as size-exclusion chromatography, sedimentation
      velocity, and multidimensional nuclear magnetic resonance (NMR) spectroscopy, it
      is shown that binding of SOS to nFGF-1 retains the protein in its monomeric
      state. In its monomeric state (complexed to SOS), n-FGF-1 shows significant cell
      proliferation activity. (15)N and (1)H chemical shift perturbation and the
      intermolecular nuclear Overhauser effects (NOEs) between SOS and nFGF-1 reveal
      that the ligand binds to the dense, positively charged cluster located in the
      groove enclosed by beta-strands 10 and 11. In addition, molecular modeling based
      on the NOEs observed for the SOS-nFGF-1 complex, indicates that SOS and heparin
      share a common binding site on the protein. In conclusion, the results of the
      present study clearly show that heparin-induced oligomerization of nFGF-1 is not
      mandatory for its cell proliferation activity.

PMID- 11967363
TI  - The role of the conserved Lys68*:Glu265 intersubunit salt bridge in aspartate
      aminotransferase kinetics: multiple forced covariant amino acid substitutions in
      natural variants.
AB  - The role of the Lys68*:Glu265 intersubunit salt bridge that is conserved (Csb) in
      all known aspartate aminotransferases (AATases), except those of animal
      cytosolic, Ac (His68*:Glu265), and plant mitochondrial, Pm (Met68*:Gln265),
      origins, was evaluated in the Escherichia coli AATase. Two double-mutant cycles,
      to K68M/E265Q and the charge reversed K68E/E265K, were characterized with the
      context dependence (C) and impact (I) formalism, previously defined for
      functional chimeric analysis. Mutations of Lys68* with Glu265 fixed are generally
      more deleterious than the converse mutations of Glu265 with Lys68* fixed, showing
      that buried negative charges have greater effects than buried positive charges in
      this context. Replacement of the charged Lys68*:Glu265 with the K68M/E265Q
      neutral pair introduces relatively small effects on the kinetic parameters. The
      differential sensitivity of k(cat)/K(M, L-Asp) and k(cat)/K(M, alpha-KG) to salt
      bridge mutagenic replacements is shown by a linear-free energy relationship, in
      which the logarithms of the latter second order rate constants are generally
      decreased by a factor of two more than are those of the former. Thus, k(cat)/K(M,
      L-Asp) and k(cat)/K(M, alpha-KG) are 133 and 442 mM(-1)s(-1) for the wild-type
      (WT) enzyme, respectively, but their relative order is reversed in the more
      severely compromised mutants (14.8 and 5.3 mM(-1)s(-1) for K68E). A Venn diagram
      illustrates apparent forced covariances of groups of amino acids that accompany
      the naturally occurring salt bridge replacements in the Pm and Ac classes. The
      more deeply rooted tree indicates that the Csb variant was the ancestral specie.

PMID- 11967365
TI  - Assessment of the ability to model proteins with leucine-rich repeats in light of
      the latest structural information.
AB  - The three-dimensional structures of leucine-rich repeat (LRR)-containing proteins
      from five different families were previously predicted based on the crystal
      structure of the ribonuclease inhibitor, using an approach that combined homology
      based modeling, structure-based sequence alignment of LRRs, and several rational
      assumptions. The structural models have been produced based on very limited
      sequence similarity, which, in general, cannot yield trustworthy predictions.
      Recently, the protein structures from three of these five families have been
      determined. In this report we estimate the quality of the modeling approach by
      comparing the models with the experimentally determined structures. The
      comparison suggests that the general architecture, curvature, "interior/exterior"
      orientations of side chains, and backbone conformation of the LRR structures can
      be predicted correctly. On the other hand, the analysis revealed that, in some
      cases, it is difficult to predict correctly the twist of the overall super
      helical structure. Taking into consideration the conclusions from these
      comparisons, we identified a new family of bacterial LRR proteins and present its
      structural model. The reliability of the LRR protein modeling suggests that it
      would be informative to apply similar modeling approaches to other classes of
      solenoid proteins.

PMID- 11967364
TI  - Replacement of Asp-162 by Ala prevents the cooperative transition by the
      substrates while enhancing the effect of the allosteric activator ATP on E. coli
      aspartate transcarbamoylase.
AB  - The available crystal structures of Escherichia coli aspartate transcarbamoylase
      (ATCase) show that the conserved residue Asp-162 from the catalytic chain
      interacts with essentially the same residues in both the T- and R-states. To
      study the role of Asp-162 in the regulatory properties of the enzyme, this
      residue has been replaced by alanine. The mutant D162A shows a 7700-fold
      reduction in the maximal observed specific activity, a twofold decrease in the
      affinity for aspartate, a loss of homotropic cooperativity, and decreased
      activation by the nucleotide effector adenosine triphosphate (ATP) compared with
      the wild-type enzyme. Small-angle X-ray scattering (SAXS) measurements reveal
      that the unliganded mutant enzyme adopts the T-quaternary structure of the wild
      type enzyme. Most strikingly, the bisubstrate analog N-phosphonacetyl-L-aspartate
      (PALA) is unable to induce the T to R quaternary structural transition, causing
      only a small alteration of the scattering pattern. In contrast, addition of the
      activator ATP in the presence of PALA causes a significant increase in the
      scattering amplitude, indicating a large quaternary structural change, although
      the mutant does not entirely convert to the wild-type R structure. Attempts at
      modeling this new conformation using rigid body movements of the catalytic
      trimers and regulatory dimers did not yield a satisfactory solution. This
      indicates that intra- and/or interchain rearrangements resulting from the
      mutation bring about domain movements not accounted for in the simple model.
      Therefore, Asp-162 appears to play a crucial role in the cooperative structural
      transition and the heterotropic regulatory properties of ATCase.

PMID- 11967366
TI  - Thermodynamic analysis of the binding of component enzymes in the assembly of the
      pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus.
AB  - The peripheral subunit-binding domain (PSBD) of the dihydrolipoyl
      acetyltransferase (E2, EC 2.3.1.12) binds tightly but mutually exclusively to
      dihydrolipoyl dehydrogenase (E3, EC 1.8.1.4) and pyruvate decarboxylase (E1, EC
      1.2.4.1) in the pyruvate dehydrogenase multienzyme complex of Bacillus
      stearothermophilus. Isothermal titration calorimetry (ITC) experiments
      demonstrated that the enthalpies of binding (DeltaH degrees ) of both E3 and E1
      with the PSBD varied with salt concentration, temperature, pH, and buffer
      composition. There is little significant difference in the free energies of
      binding (DeltaG degrees = -12.6 kcal/mol for E3 and = -12.9 kcal/mol for E1 at pH
      7.4 and 25 degrees C). However, the association with E3 was characterized by a
      small, unfavorable enthalpy change (DeltaH degrees = +2.2 kcal/mol) and a large,
      positive entropy change (TDeltaS degrees = +14.8 kcal/mol), whereas that with E1
      was accompanied by a favorable enthalpy change (DeltaH degrees = -8.4 kcal/mol)
      and a less positive entropy change (TDeltaS degrees = +4.5 kcal/mol). Values of
      DeltaC(p) of -316 cal/molK and -470 cal/molK were obtained for the binding of E3
      and E1, respectively. The value for E3 was not compatible with the DeltaC(p)
      calculated from the nonpolar surface area buried in the crystal structure of the
      E3-PSBD complex. In this instance, a large negative DeltaC(p) is not indicative
      of a classical hydrophobic interaction. In differential scanning calorimetry
      experiments, the midpoint melting temperature (T(m)) of E3 increased from 91
      degrees C to 97.1 degrees C when it was bound to PSBD, and that of E1 increased
      from 65.2 degrees C to 70.0 degrees C. These high T(m) values eliminate unfolding
      as a major source of the anomalous DeltaC(p) effects at the temperatures (10-37
      degrees C) used for the ITC experiments.

PMID- 11967367
TI  - Structural similarity to link sequence space: new potential superfamilies and
      implications for structural genomics.
AB  - The current pace of structural biology now means that protein three-dimensional
      structure can be known before protein function, making methods for assigning
      homology via structure comparison of growing importance. Previous research has
      suggested that sequence similarity after structure-based alignment is one of the
      best discriminators of homology and often functional similarity. Here, we exploit
      this observation, together with a merger of protein structure and sequence
      databases, to predict distant homologous relationships. We use the Structural
      Classification of Proteins (SCOP) database to link sequence alignments from the
      SMART and Pfam databases. We thus provide new alignments that could not be
      constructed easily in the absence of known three-dimensional structures. We then
      extend the method of Murzin (1993b) to assign statistical significance to
      sequence identities found after structural alignment and thus suggest the best
      link between diverse sequence families. We find that several distantly related
      protein sequence families can be linked with confidence, showing the approach to
      be a means for inferring homologous relationships and thus possible functions
      when proteins are of known structure but of unknown function. The analysis also
      finds several new potential superfamilies, where inspection of the associated
      alignments and superimpositions reveals conservation of unusual structural
      features or co-location of conserved amino acids and bound substrates. We discuss
      implications for Structural Genomics initiatives and for improvements to sequence
      comparison methods.

PMID- 11967368
TI  - Characterization of Ad5 E3-14.7K, an adenoviral inhibitor of apoptosis:
      structure, oligomeric state, and metal binding.
AB  - The adenovirus E3-14.7K protein, expressed early in the life cycle of human
      adenoviruses to protect the virus from the antiviral response of host cells,
      inhibits cell death mediated by TNF-alpha and FasL receptors. To better
      understand its role in cell death inhibition, we have sought to characterize the
      biophysical properties of the protein from adenovirus serotype 5 (Ad5 E3-14.7K,
      or simply 14.7K) through a variety of approaches. To obtain sufficient quantities
      of recombinantly expressed protein for biophysical characterization, we explored
      the use of various expression constructs and chaperones; fusion to MBP was by far
      the most effective at generating soluble protein. Using limited proteolysis, mass
      spectrometry, and protein-protein interaction assays, we demonstrate that the C
      terminal two-thirds of the protein, predicted to be composed of five beta-strands
      and one alpha-helix, is highly structured and binds its putative cellular
      receptors. Furthermore, using atomic absorption and ultraviolet/visible
      spectroscopies, we have studied the metal binding properties of the protein,
      providing insight into the observation that cysteine/serine mutants of 14.7K lack
      in vivo antiapoptotic activity. Lastly, results from size exclusion
      chromatography, dynamic light scattering, sucrose gradient sedimentation,
      chemical crosslinking, and electron microscopy experiments revealed that 14.7K
      exists in a stable high-order oligomeric state (nonamer) in solution.

PMID- 11967369
TI  - Presence of the cofactor speeds up folding of Desulfovibrio desulfuricans
      flavodoxin.
AB  - Flavodoxin is an alpha/beta protein with a noncovalently bound flavin
      mononucleotide (FMN) cofactor. The apo-protein adopts a structure identical to
      that of the holo-form, although there is more dynamics in the FMN-binding loops.
      The equilibrium unfolding processes of Azotobacter vinelandii apo-flavodoxin, and
      Desulfovibrio desulfuricans ATCC strain 27774 apo- and holo-flavodoxins involve
      rather stable intermediates. In contrast, we here show that both holo- and apo
      forms of flavodoxin from D. desulfuricans ATCC strain 29577 (75% sequence
      similarity with the strain 27774 protein) unfold in two-state equilibrium
      processes. Moreover, the FMN cofactor remains bound to the unfolded holo-protein.
      The folding and unfolding kinetics for holo-flavodoxin exhibit two-state
      behavior, albeit an additional slower phase is present at very low denaturant
      concentrations. The extrapolated folding time in water for holo-flavodoxin,
      approximately 280 microsec, is in excellent agreement with that predicted from
      the protein's native-state topology. Unlike the holo-protein behavior, the
      folding and unfolding reactions for apo-flavodoxin are best described by two
      kinetic phases, with rates differing approximately 15-fold, suggesting the
      presence of a kinetic intermediate. Both folding phases for apo-flavodoxin are
      orders of magnitude slower (40- and 530-fold, respectively) than that for the
      holo-protein. We conclude that polypeptide-cofactor interactions in the unfolded
      state of D. desulfuricans strain 29577 flavodoxin alter the kinetic-folding path
      towards two-state and speed up the folding reaction.

PMID- 11967370
TI  - Role of individual disulfide bonds in hen lysozyme early folding steps.
AB  - To probe the role of individual disulfide bonds in the folding kinetics of hen
      lysozyme, the variants with two mutations, C30A,C115A, C64A,C80A, and C76A,C94A,
      were constructed. The corresponding proteins, each lacking one disulfide bond,
      were produced in Escherichia coli as inclusion bodies and solubilized, purified,
      and renatured/oxidized using original protocols. Their enzymatic, spectral, and
      hydrodynamic characteristics confirmed that their conformations were very similar
      to that of native wild-type (WT) lysozyme. Stopped-flow studies on the
      renaturation of these guanidine-unfolded proteins with their three disulfides
      intact showed that, for the three variants, the native far-UV ellipticity was
      regained in a burst phase within the 4-ms instrument dead-time. The transient
      overshoots of far-UV ellipticity and tryptophan fluorescence that follow the
      burst phase, as well as the kinetics of transient 8-anilino-1-naphthalene
      sulfonic acid (ANS) binding, were diversely affected depending on the variant.
      Together with previous reports on the folding kinetics of WT lysozyme
      carboxymethylated on cysteines 6 and 127, detailed analysis of the kinetics
      showed that (1) none of the disulfide bonds were indispensable for the rapid
      formation (<4 ms) of the native-like secondary structure; (2) the two intra-alpha
      domain disulfides (C6-C127 and C30-C115) must be simultaneously present to
      generate the trapped intermediate responsible for the slow folding population
      observed in WT lysozyme; and (3) the intra-beta-domain (C64-C80) and the inter
      alphabeta-domains (C76-C94) disulfides do not affect the kinetics of formation of
      the trapped intermediate but are involved in its stability.

PMID- 11967371
TI  - Dynamics of green fluorescent protein mutant2 in solution, on spin-coated
      glasses, and encapsulated in wet silica gels.
AB  - Single-molecule experiments are performed by investigating spectroscopic
      properties of molecules either diffusing in and out of the observation volume or
      fixed in space by different immobilization procedures. To evaluate the effect of
      immobilization methods on the structural and dynamic properties of proteins, a
      highly fluorescent mutant of the green fluorescent protein, GFPmut2, was
      spectroscopically characterized in bulk solutions, dispersed on etched glasses,
      and encapsulated in wet, nanoporous silica gels. The emission spectrum, the
      fluorescence lifetimes, the anisotropy, and the rotational correlation time of
      GFPmut2, encapsulated in silica gels, are very similar to those obtained in
      solution. This finding indicates that the gel matrix does not alter the protein
      conformation and dynamics. In contrast, the fluorescence lifetimes of GFPmut2 on
      glasses are two-to fourfold higher and the fluorescence anisotropy decays yield
      almost no phase shifts. This indicates that the interaction of the protein with
      the bare glass surface induces a significant structural perturbation and severely
      restricts the rotational motion. Single molecules of GFPmut2 on glasses or in
      silica gels, identified by confocal image analysis, show a significant stability
      to illumination with bleaching times of the order of 90 and 60 sec, respectively.
      Overall, these data indicate that silica gels represent an ideal matrix for
      following biologically relevant events at a single molecule level.

PMID- 11967372
TI  - Novel alpha7-like nicotinic acetylcholine receptor subunits in the nematode
      Caenorhabditis elegans.
AB  - We have used reverse-transcription-polymerase chain reaction (RT-PCR) and DNA
      sequencing techniques to confirm the transcription of seven (six alpha and one
      non-alpha) novel candidate nicotinic acetylcholine receptor (nAChR) subunit
      encoding genes identified in the genome sequence of the nematode Caenorhabditis
      elegans. Compared to vertebrate nAChR subunits, they most closely resemble the
      homomer-forming, neuronal alpha7 subunit. Comparison of the predicted amino acid
      sequences of the new nAChR subunits with those described previously in C. elegans
      reveals five subunits (four alpha and one non-alpha) which resemble the DEG-3
      like group of subunits. To date, this highly divergent nAChR subunit group is
      unique to C. elegans. ACR-22 is the first non-alpha member of the DEG-3-like
      group of subunits to be identified. Two new members of the related ACR-16-like
      nAChR group of subunits have also been shown to be transcribed, making the ACR-16
      like subunit group the largest in C. elegans. Residues in the alpha subunit
      second transmembrane region (M2) which contribute to the channel lining show
      variations with implications for channel function. For example, in ACR-22, the
      highly conserved 0' lysine of M2 is replaced by histidine. Restrained molecular
      dynamics simulations have been used to generate molecular models of homo
      pentameric M2 helix bundles for the novel subunits, enabling identification and
      display of pore-lining and protein interface residues. The number and diversity
      of genes encoding C. elegans nAChR subunits with similarities to the homomer
      forming vertebrate alpha7 subunits and the identification of related non-alpha
      subunits, only found in C. elegans to date, suggest that at least some of these
      subunits may contribute to heteromers in vivo.

PMID- 11967373
TI  - Structural changes and molecular interactions of hydrophobin SC3 in solution and
      on a hydrophobic surface.
AB  - The hydrophobin SC3 belongs to a class of small proteins functioning in the
      growth and development of fungi. Its unique amphipathic property and remarkable
      surface activity make it interesting not only for biological studies but also for
      medical and industrial applications. Biophysical studies have revealed that SC3
      possesses at least three distinct conformations, named "soluble-state SC3" for
      the protein in solution, and "alpha-helical-state SC3" and "beta-sheet-state SC3"
      for the different states of the protein associated at a hydrophobic-water
      interface. The present fluorescence study shows that the microenvironment of the
      dansyl-labeled N terminus of soluble-state SC3 is relatively hydrophobic, whereas
      it is hydrophilic for alpha-helical-state and beta-sheet-state SC3. Fluorescence
      collisional quenching indicates that the N terminus of soluble-state SC3 is more
      solvent-accessible than those of alpha-helical-state and beta-sheet-state SC3,
      with Stern-Volmer constants for acrylamide of 4.63, 0.02, and 0.2 M(-1) for the
      different states, respectively. Fluorescence resonance energy transfer
      measurements show that soluble-state SC3 tends to associate in solution but
      dissociates in TFA. Fluorescence energy transfer was eliminated by conversion of
      soluble-state SC3 to alpha-helical-state SC3 on a hydrophobic surface, indicating
      a spatial separation of the molecules in this state. By inducing the beta-sheet
      state, structural changes were observed, both by CD and by fluorescence, that
      could be fit to two exponentials with lifetimes of about 10 min and 4 h.
      Molecules in the beta-sheet state also underwent a slow change in spatial
      proximity on the hydrophobic surface, as revealed by the reappearance of
      fluorescence resonance energy transfer in time.

PMID- 11967374
TI  - Structural similarity of the covalent complexes formed between the serpin
      plasminogen activator inhibitor-1 and the arginine-specific proteinases trypsin,
      LMW u-PA, HMW u-PA, and t-PA: use of site-specific fluorescent probes of local
      environment.
AB  - We have used two fluorescent probes, NBD and dansyl, attached site-specifically
      to the serpin plasminogen activator inhibitor-1 (PAI-1) to address the question
      of whether a common mechanism of proteinase translocation and full insertion of
      the reactive center loop is used by PAI-1 when it forms covalent SDS-stable
      complexes with four arginine-specific proteinases, which differ markedly in size
      and domain composition. Single-cysteine residues were incorporated at position
      119 or 302 as sites for specific reporter labeling. These are positions
      approximately 30 A apart that allow discrimination between different types of
      complex structure. Fluorescent derivatives were prepared for each of these
      variants using both NBD and dansyl as reporters of local perturbations. Spectra
      of native and cleaved forms also allowed discrimination between direct proteinase
      induced changes and effects solely due to conformational change within the
      serpin. Covalent complexes of these derivatized PAI-1 species were made with the
      proteinases trypsin, LMW u-PA, HMW u-PA, and t-PA. Whereas only minor
      perturbations of either NBD and dansyl were found for almost all complexes when
      label was at position 119, major perturbations in both wavelength maximum (blue
      shifts) and quantum yield (both increases and decreases) were found for all
      complexes for both NBD and dansyl at position 302. This is consistent with all
      four complexes having similar location of the proteinase catalytic domain and
      hence with all four using the same mechanism of full-loop insertion with
      consequent distortion of the proteinase wedged in at the bottom of the serpin.

PMID- 11967376
TI  - Self-assembly of the hydrophobin SC3 proceeds via two structural intermediates.
AB  - Hydrophobins self assemble into amphipathic films at hydrophobic-hydrophilic
      interfaces. These proteins are involved in a broad range of processes in fungal
      development. We have studied the conformational changes that accompany the self
      assembly of the hydrophobin SC3 with polarization-modulation infrared reflection
      absorption spectroscopy, attenuated total reflection Fourier transform infrared
      spectroscopy, and circular dichroism, and related them to changes in morphology
      as observed by electron microcopy. Three states of SC3 have been
      spectroscopically identified previously as follows: the monomeric state, the
      alpha-helical state that is formed upon binding to a hydrophobic solid, and the
      beta-sheet state, which is formed at the air-water interface. Here, we show that
      the formation of the beta-sheet state of SC3 proceeds via two intermediates. The
      first intermediate has an infrared spectrum indistinguishable from that of the
      alpha-helical state of SC3. The second intermediate is rich in beta-sheet
      structure and has a featureless appearance under the electron microscope. The end
      state has the same secondary structure, but is characterized by the familiar 10
      nm-wide rodlets.

PMID- 11967375
TI  - Stability and interactions of the amino-terminal domain of ClpB from Escherichia
      coli.
AB  - ClpB is a member of a multichaperone system in Escherichia coli (with DnaK, DnaJ,
      and GrpE) that reactivates aggregated proteins. The sequence of ClpB contains two
      ATP-binding regions that are enclosed between the N- and C-terminal extensions.
      Whereas it has been found that the N-terminal region of ClpB is essential for the
      chaperone activity, the structure of this region is not known, and its
      biochemical properties have not been studied. We expressed and purified the N
      terminal fragment of ClpB (residues 1-147). Circular dichroism of the isolated N
      terminal region showed a high content of alpha-helical structure. Differential
      scanning calorimetry showed that the N-terminal region of ClpB is
      thermodynamically stable and contains a single folding domain. The N-terminal
      domain is monomeric, as determined by gel-filtration chromatography, and the
      elution profile of the N-terminal domain does not change in the presence of the N
      terminally truncated ClpB (ClpBDeltaN). This indicates that the N-terminal domain
      does not form strong contacts with ClpBDeltaN. Consistently, addition of the
      separated N-terminal domain does not reverse an inhibition of ATPase activity of
      ClpBDeltaN in the presence of casein. As shown by ELISA measurements, full-length
      ClpB and ClpBDeltaN bind protein substrates (casein, inactivated luciferase) with
      similar affinity. We also found that the isolated N-terminal domain of ClpB
      interacts with heat-inactivated luciferase. Taken together, our results indicate
      that the N-terminal fragment of ClpB forms a distinct domain that is not strongly
      associated with the ClpB core and is not required for ClpB interactions with
      other proteins, but may be involved in recognition of protein substrates.

PMID- 11967377
TI  - Functionally relevant motions of haloalkane dehalogenases occur in the
      specificity-modulating cap domains.
AB  - One-nanosecond molecular dynamics trajectories of three haloalkane dehalogenases
      (DhlA, LinB, and DhaA) are compared. The main domain was rigid in all three
      dehalogenases, whereas the substrate specificity-modulating cap domains showed
      considerably higher mobility. The functionally relevant motions were spread over
      the entire cap domain in DhlA, whereas they were more localized in LinB and DhaA.
      The highest amplitude of essential motions of DhlA was noted in the alpha4'-helix
      loop-alpha4-helix region, formerly proposed to participate in the large
      conformation change needed for product release. The highest amplitude of
      essential motions of LinB and DhaA was observed in the random coil before helix
      4, linking two domains of these proteins. This flexibility is the consequence of
      the modular composition of haloalkane dehalogenases. Two members of the catalytic
      triad, that is, the nucleophile and the base, showed a very high level of
      rigidity in all three dehalogenases. This rigidity is essential for their
      function. One of the halide-stabilizing residues, important for the catalysis,
      shows significantly higher flexibility in DhlA compared with LinB and DhaA.
      Enhanced flexibility may be required for destabilization of the electrostatic
      interactions during the release of the halide ion from the deeply buried active
      site of DhlA. The exchange of water molecules between the enzyme active site and
      bulk solvent was very different among the three dehalogenases. The differences
      could be related to the flexibility of the cap domains and to the number of
      entrance tunnels.

PMID- 11967378
TI  - Development of a cytokine analog with enhanced stability using computational
      ultrahigh throughput screening.
AB  - Granulocyte-colony stimulating factor (G-CSF) is used worldwide to prevent
      neutropenia caused by high-dose chemotherapy. It has limited stability, strict
      formulation and storage requirements, and because of poor oral absorption must be
      administered by injection (typically daily). Thus, there is significant interest
      in developing analogs with improved pharmacological properties. We used our
      ultrahigh throughput computational screening method to improve the
      physicochemical characteristics of G-CSF. Improving these properties can make a
      molecule more robust, enhance its shelf life, or make it more amenable to
      alternate delivery systems and formulations. It can also affect clinically
      important features such as pharmacokinetics. Residues in the buried core were
      selected for optimization to minimize changes to the surface, thereby maintaining
      the active site and limiting the designed protein's potential for antigenicity.
      Using a structure that was homology modeled from bovine G-CSF, core designs of 25
      34 residues were completed, corresponding to 10(21)-10(28) sequences screened.
      The optimal sequence from each design was selected for biophysical
      characterization and experimental testing; each had 10-14 mutations. The designed
      proteins showed enhanced thermal stabilities of up to 13 degrees C, displayed
      five-to 10-fold improvements in shelf life, and were biologically active in cell
      proliferation assays and in a neutropenic mouse model. Pharmacokinetic studies in
      monkeys showed that subcutaneous injection of the designed analogs results in
      greater systemic exposure, probably attributable to improved absorption from the
      subcutaneous compartment. These results show that our computational method can be
      used to develop improved pharmaceuticals and illustrate its utility as a powerful
      protein design tool.

PMID- 11967379
TI  - Folding and stability of the b subunit of the F(1)F(0) ATP synthase.
AB  - The F(1)F(0) ATP synthase is a reversible molecular motor that employs a rotary
      catalytic cycle to couple a chemiosmotic membrane potential to the
      formation/hydrolysis of ATP. The multisubunit enzyme contains two copies of the b
      subunit that form a homodimer as part of a narrow, peripheral stalk structure
      that connects the membrane (F(0)) and soluble (F(1)) sectors. The three
      dimensional structure of the b subunit is unknown making the nature of any
      interactions or conformational changes within the F(1)F(0) complex difficult to
      interpret. We have used circular dichroism and analytical ultracentrifugation
      analyses of a series of N- and C-terminal truncated b proteins to investigate its
      stability and structure. Thermal denaturation of the b constructs exhibited
      distinct two-state, cooperative unfolding with T(m) values between 30 and 40
      degrees C. CD spectra for the region comprising residues 53-122 (b(53-122))
      showed theta;(222)/theta;(208) = 0.99, which reduced to 0.92 in the presence of
      the hydrophobic solvent trifluoroethanol. Thermodynamic parameters for b(53-122)
      (DeltaG, DeltaH and DeltaC(p)) were similar to those reported for several
      nonideal, coiled-coil proteins. Together these results are most consistent with a
      noncanonical and unstable parallel coiled-coil at the interface of the b dimer.

PMID- 11967380
TI  - Subunit organization in cytoplasmic dynein subcomplexes.
AB  - Because cytoplasmic dynein plays numerous critical roles in eukaryotic cells,
      determining the subunit composition and the organization and functions of the
      subunits within dynein are important goals. This has been difficult partly
      because of accessory polypeptide heterogeneity of dynein populations. The motor
      domain containing heavy chains of cytoplasmic dynein are associated with multiple
      intermediate, light intermediate, and light chain accessory polypeptides. We
      examined the organization of these subunits within cytoplasmic dynein by
      separating the molecule into two distinct subcomplexes. These subcomplexes were
      competent to reassemble into a molecule with dynein-like properties. One
      subcomplex was composed of the dynein heavy and light intermediate chains whereas
      the other subcomplex was composed of the intermediate and light chains. The
      intermediate and light chain subcomplex could be further separated into two
      pools, only one of which contained dynein light chains. The two pools had
      distinct intermediate chain compositions, suggesting that intermediate chain
      isoforms have different light chain-binding properties. When the two intermediate
      chain pools were characterized by analytical velocity sedimentation, at least
      four molecular components were seen: intermediate chain monomers, intermediate
      chain dimers, intermediate chain monomers with bound light chains, and a mixture
      of intermediate chain dimers with assorted bound light chains. These data provide
      new insights into the compositional heterogeneity and assembly of the cytoplasmic
      dynein complex and suggest that individual dynein molecules have distinct
      molecular compositions in vivo.

PMID- 11967381
TI  - Excision of a proposed electron transfer pathway in cytochrome c peroxidase and
      its replacement by a ligand-binding channel.
AB  - A previously proposed electron transfer (ET) pathway in the heme enzyme
      cytochrome c peroxidase has been excised from the structure, leaving an open
      ligand-binding channel in its place. Earlier studies on cavity mutants of this
      enzyme have revealed structural plasticity in this region of the molecule.
      Analysis of these structures has allowed the design of a variant in which the
      specific section of protein backbone representing a previously proposed ET
      pathway is accurately extracted from the protein. A crystal structure verified
      the creation of an open channel that overlays the removed segment, extending from
      the surface of the protein to the heme at the core of the protein. A number of
      heterocyclic cations were found to bind to the proximal-channel mutant with
      affinities that can be rationalized based on the structures. It is proposed that
      small ligands bind more weakly to the proximal-channel mutant than to the W191G
      cavity due to an increased off rate of the open channel, whereas larger ligands
      are able to bind to the channel mutant without inducing large conformational
      changes. The structure of benzimidazole bound to the proximal-channel mutant
      shows that the ligand accurately overlays the position of the tryptophan radical
      center that was removed from the wild-type enzyme and displaces four of the eight
      ordered solvent molecules seen in the empty cavity. Ligand binding also caused a
      small rearrangement of the redesigned protein loop, perhaps as a result of
      improved electrostatic interactions with the ligand. The engineered channel
      offers the potential for introducing synthetic replacements for the removed
      structure, such as sensitizer-linked substrates. These installed "molecular
      wires" could be used to rapidly initiate reactions, trap reactive intermediates,
      or answer unresolved questions about ET pathways.

PMID- 11967382
TI  - Salt-induced stabilization of apoflavodoxin at neutral pH is mediated through
      cation-specific effects.
AB  - Electrostatic contributions to the conformational stability of apoflavodoxin were
      studied by measurement of the proton and salt-linked stability of this highly
      acidic protein with urea and temperature denaturation. Structure-based
      calculations of electrostatic Gibbs free energy were performed in parallel over a
      range of pH values and salt concentrations with an empirical continuum method.
      The stability of apoflavodoxin was higher near the isoelectric point (pH 4) than
      at neutral pH. This behavior was captured quantitatively by the structure-based
      calculations. In addition, the calculations showed that increasing salt
      concentration in the range of 0 to 500 mM stabilized the protein, which was
      confirmed experimentally. The effects of salts on stability were strongly
      dependent on cationic species: K(+), Na(+), Ca(2+), and Mg(2+) exerted similar
      effects, much different from the effect measured in the presence of the bulky
      choline cation. Thus cations bind weakly to the negatively charged surface of
      apoflavodoxin. The similar magnitude of the effects exerted by different cations
      indicates that their hydration shells are not disrupted significantly by
      interactions with the protein. Site-directed mutagenesis of selected residues and
      the analysis of truncation variants indicate that cation binding is not site
      specific and that the cation-binding regions are located in the central region of
      the protein sequence. Three-state analysis of the thermal denaturation indicates
      that the equilibrium intermediate populated during thermal unfolding is competent
      to bind cations. The unusual increase in the stability of apoflavodoxin at
      neutral pH affected by salts is likely to be a common property among highly
      acidic proteins.

PMID- 11967383
TI  - A model of the replication fork blocking protein Fob1p based on the catalytic
      core domain of retroviral integrases.
AB  - The replication fork blocks are common in both prokaryotes and eukaryotes. In
      most cases, these blocks are associated with increased levels of mitotic
      recombination. One of the best-characterized replication fork blocks in
      eukaryotes is found in ribosomal DNA (rDNA) repeats of Saccharomyces cerevisiae.
      It has been shown that the replication fork blocking protein Fob1p regulates the
      recombination rate and the number of rDNA copies in S. cerevisiae, but the
      mechanistic aspects of these events are still poorly understood. Sequence profile
      searches revealed that Fob1p is related to retroviral integrases. Subsequently,
      the catalytic domain of HIV-1 integrase was used as a template to build a
      reliable three-dimensional model of Fob1p. Structural insights from this study
      may be useful in explaining Fob1p-mediated formation of extrachromosomal rDNA
      circles that accelerate aging in yeast and recombination events that lead to
      expansion or contraction of rDNA.

PMID- 11967384
TI  - Building a stronger foundation: improved antithrombin therapy with bivalirudin in
      percutaneous coronary intervention.

PMID- 11967385
TI  - Acute coronary syndromes: a focus on thrombin.

PMID- 11967386
TI  - Direct versus indirect thrombin inhibition in percutaneous coronary intervention.

PMID- 11967388
TI  - The implications of renal impairment among patients undergoing percutaneous
      coronary intervention.
AB  - The clinical implications of even mild impairment of renal function in
      percutaneous coronary interventions (PCI) have, to date, been poorly appreciated.
      The progressive loss of renal function is marked by the onset of a thrombo
      inflammatory state not unlike what occurs in progressive coronary artery disease
      (CAD). In the presence of renal insufficiency, procedural success is reduced,
      peri-procedural myocardial infarction (MI) is more frequent and increased late
      mortality, myocardial ischemia and target vessel revascularization are more
      common. Vessel stenting reduces the rate of target vessel revascularization in
      renal failure patients, but fails to impact the frequency of peri-procedural
      ischemic events. Consequently, a rational, evidence-based approach to adjunctive
      anticoagulation in renal failure patients undergoing PCI is warranted if per
      procedural ischemic events are to be better managed. Unfortunately, current
      recommendations are hampered by a paucity of clinical trial evidence specifically
      examining the efficacy of available therapies. In an attempt to go beyond this
      lack of clinical evidence, some therapeutic insight may be drawn from the known
      hemostatic derangements associated with renal impairment. These changes include a
      well-described decreased in platelet aggregatory activity and an increase in
      thrombin generation. While more definitive clinical trial evidence of adjunctive
      anticoagulation efficacy among patients with renal impairment is in process, this
      article will briefly review the pathophysiological changes associated with renal
      impairment, as well as the evidence supporting each of the current therapeutic
      options available to the interventional cardiologist.

PMID- 11967387
TI  - Overcoming heparin limitations in high-risk percutaneous coronary intervention:
      the alternative strategy-- replacing heparin with bivalirudin.

PMID- 11967389
TI  - Thrombocytopenia and outcome in invasive cardiology.

PMID- 11967390
TI  - Increasing benefit, reducing risk: focusing on hemorrhagic complications in
      percutaneous coronary intervention.

PMID- 11967392
TI  - Editorial.

PMID- 11967393
TI  - Parity for mental health and substance abuse care under managed care.
AB  - BACKGROUND: Parity in insurance coverage for mental health and substance abuse
      has been a key goal of mental health and substance abuse care advocates in the
      United States during most of the past 20 years. The push for parity began during
      the era of indemnity insurance and fee for service payment when benefit design
      was the main rationing device in health care. The central economic argument for
      enacting legislation aimed at regulating the insurance benefit was to address
      market failure stemming from adverse selection. The case against parity was based
      on inefficiency related to moral hazard. Empirical analyses provided evidence
      that ambulatory mental health services were considerably more responsive to the
      terms of insurance than were ambulatory medical services. AIMS: Our goal in this
      research is to reexamine the economics of parity in the light of recent changes
      in the delivery of health care in the United States. Specifically managed care
      has fundamentally altered the way in which health services are rationed. Benefit
      design is now only one mechanism among many that are used to allocate health care
      resources and control costs. We examine the implication of these changes for
      policies aimed at achieving parity in insurance coverage. METHOD: We develop a
      theoretical approach to characterizing rationing under managed care. We then
      analyze the traditional efficiency concerns in insurance, adverse selection and
      moral hazard in the context of policy aimed at regulating health and mental
      health benefits under private insurance. RESULTS: We show that since managed care
      controls costs and utilization in new ways parity in benefit design no longer
      implies equal access to and quality of mental health and substance abuse care.
      Because costs are controlled by management under managed care and not primarily
      by out of pocket prices paid by consumers, demand response recedes as an
      efficiency argument against parity. At the same time parity in benefit design may
      accomplish less with respect to providing a remedy to problems related to adverse
      selection.

PMID- 11967391
TI  - Frequency and costs of ischemic and bleeding complications after percutaneous
      coronary interventions: rationale for new antithrombotic agents.

PMID- 11967394
TI  - Mental health, absenteeism and earnings at a large manufacturing worksite.
AB  - BACKGROUND: A few recent studies have examined the relationship between mental
      illness and labor market variables. The findings are inconsistent, however, and
      leave unanswered many questions concerning both the nature and magnitude of the
      relationship. AIMS OF THE STUDY: A recently available worksite-based data set is
      analyzed to explore the relationship between symptoms of emotional and
      psychological problems and employee absenteeism and earnings among employees at a
      large US worksite. METHODS: The analysis was based on data collected through a
      random and anonymous survey of workers at a large US manufacturing worksite. Two
      measures of absenteeism are combined - days absent during the past 30 days due to
      sickness or injury and days absent during the past 30 days because the employee
      did not want to be at work - to create both a dichotomous (i.e., ever absent) and
      a continuous (i.e., number of days absent) absenteeism variable. Annual earnings
      were measured as personal earnings from the primary job. Various statistical
      models were tested to determine the independent and joint (with alcohol and
      illicit drug use) relationship between symptoms of emotional problems and labor
      market variables. RESULTS: The analysis consistently finds that workers who
      report symptoms of emotional/psychological problems have higher absenteeism and
      lower earnings than otherwise similar coworkers. This finding is robust to model
      specification and to the inclusion of comorbid conditions such as alcohol and
      illicit drug use. DISCUSSION: This study contributes new information to the
      literature in this area by estimating the effects of emotional/psychological
      symptoms on two important labor market variables: absenteeism and earnings.
      Several specifications of the absenteeism and earnings equations were estimated
      to test the independent effect of emotional symptoms and the joint effects of
      emotional symptoms and other comorbid conditions. The results suggest that
      employers should consider the productivity losses associated with workers' mental
      health when designing worksite-based programs such as employee assistance
      programs (EAPs). LIMITATIONS: Unlike national surveys of households or
      individuals, the sample does not include unemployed individuals or those outside
      the labor force. Therefore, the decision to participate in the labor market can
      not be modeled. In addition, the study relies on voluntary self-reported survey
      data that may suffer from underreporting of substance use and emotional symptoms.
      Although respondents were repeatedly assured about confidentiality, if
      underreporting does exist, it may be more acute than in household surveys because
      respondents may be more worried about job loss if they self-report drug or
      alcohol use at the worksite. CONCLUSIONS: All four measures of emotional symptoms
      had a positive and statistically significant relationship with absenteeism and a
      negative and statistically significant relationship with personal earnings. These
      findings were robust across all specifications, even when the effects of other
      potentially confounding factors (i.e., alcohol and drug use variables) are
      included. In addition, the number of days intoxicated and cigarette use in the
      past year appear to be significantly related to earnings even after controlling
      for emotional symptoms. Finally, the explanatory power of the models is
      relatively high for cross-sectional data, especially for the earnings
      regressions. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The findings from
      this worksite suggest that employers might do well to reassess the priorities of
      their EAPs and consider directing more of their resources to diagnosing and
      assisting employees with emotional and psychological distress. IMPLICATIONS FOR
      HEALTH POLICY FORMULATION: It is strongly suggestive that mental health status is
      related to absenteeism and earnings for employees at this worksite. However, most
      employer-based programs and policies are designed to dissuade the use of alcohol
      and illicit drugs by workers (e.g., employee drug and alcohol testing) rather
      than addressing other employee behaviors and problems. IMPLICATIONS FOR FURTHER
      RESEARCH: Numerous opportunities are present to collect similar data from other
      worksites and settings to determine whether these models and results are robust.

PMID- 11967395
TI  - Child outpatient mental health service use: why doesn't insurance matter?
AB  - BACKGROUND: Several recent studies of child outpatient mental health service use
      in the US have shown that having private insurance has no effect on the
      propensity to use services. Some studies also find that public coverage has no
      beneficial effect relative to no insurance. AIMS: This study explores several
      potential explanations, including inadequate measurement of mental health status,
      bandwagon effects, unobservable heterogeneity and public sector substitution for
      private services, for the lack of an effect of private insurance on service use.
      METHODS: We use secondary analysis of data from the three mainland US sites of
      NIMH's 1992 field trial of the Cooperative Agreement for Methodological Research
      for Multi-Site Surveys of Mental Disorders in Child and Adolescent Populations
      (MECA) Study. We examine whether or not a subject used any mental health service,
      school-based mental health services or outpatient mental health services, and the
      number of outpatient visits among users. We also examine use of general medical
      services as a check on our results. We conduct regression analysis; instrumental
      variables analysis, using instruments based on employment and parental history of
      mental health problems to identify insurance choice, and bivariate probit
      analysis to examine multiservice use. RESULTS: We find evidence that children
      with private health insurance have fewer observable (measured) mental health
      problems. They also appear to have a lower unobservable (latent) propensity to
      use mental health services than do children without coverage and those with
      Medicaid coverage. Unobserved differences in mental health status that relate to
      insurance choice are found to contribute to the absence of a positive effect for
      private insurance relative to no coverage in service use regressions. We find no
      evidence to suggest that differences in attitudes or differences in service
      availability in children's census tracts of residence explain the non-effect of
      insurance. Finally, we find that the lack of a difference is not a consequence of
      substitution of school-based for office-based services. School-based and office
      based specialty mental health services are complements rather than substitutes.
      School-based services are used by the same children who use office-based
      services, even after controlling for mental health status. DISCUSSION: Our
      results are consistent with at least two explanations. First, limits on coverage
      under private insurance may discourage families who anticipate a need for child
      mental health services from purchasing such insurance. Second, publicly funded
      services may be readily available substitutes for private services, so that lack
      of insurance is not a barrier to adequate care. Despite the richness of data in
      the MECA dataset, cross-sectional data based on epidemiological surveys do not
      appear to be sufficient to fully understand the surprising result that insurance
      does not enable access to care. IMPLICATIONS FOR POLICY AND RESEARCH: Limits on
      coverage under private mental health insurance combined with a relatively
      extensive system of public mental health coverage have apparently generated a
      situation where there is no observed advantage to the marginal family of
      obtaining private mental health insurance coverage. Further research using
      longitudinal data is needed to better understand the nature of selection in the
      child mental health insurance market. Further research using better measures of
      the nature of treatment provided in different settings is needed to better
      understand how the private and public mental health systems operate.

PMID- 11967396
TI  - The public sector and mental health parity: time for inclusion.
AB  - BACKGROUND: In the United States, there is an uneasy division of responsibility
      for financing mental health care. For most illnesses, employer-sponsored health
      insurance and the large federal health insurance programs (Medicare, Medicaid)
      cover the costs of care. However, most employer-sponsored plans and Medicare
      provide only limited coverage for treatment of mental illness. A possible cause
      and result of this limited coverage in mental health is that states, and in some
      cases local (county) governments, finance a separate system of mental health
      care. This separate "public mental health system" provides a "safety net" of care
      for indigent individuals needing mental health care. However, there are potential
      negative consequences of maintaining separate systems. Continuity of treatment
      between systems may be impaired, and costs may be higher due to duplicate
      administrative costs. Maintaining a separate system managed by government may
      exacerbate the stigma associated with mental illness treatment. Most
      significantly, since eligibility for care may be linked to poverty status, and
      since having a serious mental illness may preclude regaining private coverage,
      maintaining a separate system may contribute to the poverty rate among persons
      with mental illnesses. AIMS OF THE PAPER: These potential problems have not been
      widely considered, perhaps because other problems and controversies in mental
      health care have captured our attention. In particular, controversies over
      deinstitutionalization in mental health have dominated the policy debate,
      especially when linked to related problems. These have included conflicts over
      authority and financial responsibility among federal, state and local
      governments, sensationalized media coverage of incidents involving people with
      mental illness, problems with siting community facilities, concern about mental
      illness among prisoners and the like. However, with the substantial reform of
      public mental health care in some states and localities, it is now possible to
      consider the implications of public and private integration. This paper considers
      such an approach. METHODS: This paper addresses the question of public and
      private integration, considering the state of Ohio as a case study. Ohio is a
      large state (population 11.2 million) and shares demographic, cultural and
      political characteristics with many other states. Ohio's successful experience
      implementing community mental health reform makes it a good candidate to use in
      evaluating issues in the potential integration of insurance-paid and public
      mental health care. RESULTS: The analysis indicates that the resources now used
      in Ohio's public system may be sufficient to support insurance financing of
      inpatient and ambulatory mental health treatment (the types of health care
      usually paid by insurance) while maintaining supportive services (e.g. housing,
      crisis care) as a residual safety net. DISCUSSION: At the current time, these
      resources are in state and local mental health budgets, and in the Medicaid
      program that finances health care for low income and disabled individuals. The
      analysis indicates that the aggregate level of resources expended on inpatient
      and ambulatory mental health treatment are substantially greater than
      expenditures for such care in an insurance plan for Ohio State employees. A
      substantial limitation of the analysis is that it is not possible to compare the
      need for care in a relatively healthy employed population versus a poor and
      disabled population. CONCLUSION: The paper concludes that there are substantial
      structural, economic and social problems associated with the "two-tiered" system
      of commercial/employer-paid insurance and public mental health care in the United
      States. Examining data from one state's public system, the paper further
      concludes that it might be feasible to finance a single system of acute and
      ambulatory mental health benefits, if public resources were redeployed and
      private contributions were continued. IMPLICATIONS FOR POLICY AND RESEARCH: Given
      the substantial problems associated with the two-tiered American approach to
      mental health care, further consideration and analyses of the feasibility of
      public and private integration are suggested. Given the complexity of this
      effort, much more sophisticated analysis is needed. However, given the
      possibility that sufficient resources may now be available to accomplish
      integration, further work is suggested.

PMID- 11967397
TI  - The role of mental health service research in promoting effective treatment for
      adults with schizophrenia*
AB  - BACKGROUND: Significant gaps exist between scientific knowledge about the
      efficacy of treatments for mental disorders and the availability of efficacious
      treatments in routine practice. Mental health service research can help bridge
      this gap between basic clinical research and the usual care afforded adults with
      mental disorders. AIMS: To illustrate this potential, data on the efficacy of
      treatment for schizophrenia are reviewed. METHODS: The treatments reviewed
      include pharmacotherapies, psychological interventions, family interventions,
      vocational rehabilitation and assertive community treatment and case management.
      Using treatment recommendations based upon outcome data about these treatments
      and the results of a large survey of usual care for schizophrenia from the
      Schizophrenia Patient Outcomes Research Team (PORT) project, examples of current
      deficiencies in the usual treatment of adult mental disorders and relevant
      questions that need to be addressed by mental health services research are
      identified. RESULTS: Major deficiencies in treatment that were identified include
      inappropriate dosing with antipsychotic agents, underutilization of adjunctive
      antidepressant therapy, very low rates of prescription of psychosocial
      interventions and lack of continuity between inpatient and outpatient settings.
      DISCUSSION: These findings raise serious concerns about access to care and the
      appropriateness and quality of care that is offered. IMPLICATIONS: This knowledge
      about what treatments work for schizophrenia and the patterns of current care
      suggest the following major questions be addressed by mental health services
      research: What is the nature of care currently being offered adults with mental
      disorders? To what degree does this care measure up to scientifically derived
      quality of care and treatment standards? What is the effectiveness of new
      technologies under usual practice conditions? For which patients are they cost
      effective and under what conditions? How should financial incentives be
      structured within systems of care to promote the most cost-effective use of new
      technologies? How should service systems themselves be organized to promote
      appropriate access and utilization? What educational, organizational and
      financing interventions promote adoption of effective interventions? Do we have
      valid methods for assessing quality of care? What strategies (interventions) are
      effective at improving the quality of care? In addition, we need to develop
      strategies that transfer mental health services research technologies into
      practice. These include: (i) development of outcome measures that meet scientific
      standards and that are practical for general application in service systems to
      facilitate "outcome management"; (ii) development of quality of care assessment
      methodologies that are practical and scientifically sound and (iii) cost
      effectiveness methodologies. Mental health services research can facilitate the
      translation of knowledge developed from basic clinical research into more
      effective systems of care. The tools used by health services research to this end
      include examination of patterns of usual care in relation to scientifically
      established standards of efficacious care, interventions to improve the
      effectiveness of care and examination of the impacts of the organization and
      financing of services on outcomes and costs. In short, mental health service
      research holds high on its agenda the translation of basic and clinical research
      into practice. All of us must face the challenges posed by our rapidly changing
      mental health care system, changes driven not only by managed care and cost
      containment, but by exciting new developments in the treatment of mental
      disorders. We take on these challenges as researchers, clinicians,
      administrators, patients, families and taxpayers. Here I seek to provide a
      perspective on what we know about the treatment of adults with mental disorders
      and to discuss the implications of this knowledge for the work of mental health
      service research. Each of us has a particular window on this scene; mine is
      primarily that of a clinical mental health services researcher who studies
      schizophrenia. I will briefly summarize current knowledge about the efficacy of
      treatments for schizophrenia and the services research questions that this
      knowledge raises in its translation to clinical practice. The lessons from this
      examination readily generalize to the treatment of other adult mental disorders.

PMID- 11967398
TI  - Commentary.

PMID- 11967399
TI  - J. Mental Health Policy Econ. 1: 209 (1998). Cost-Outcome Methods for Mental
      Health. By William A. Hargreaves, Martha Shumaway, The-wei Hu, and Brian Cuffel.
      San Diego: Academic Press, 1998.

PMID- 11967400
TI  - Editorial.

PMID- 11967401
TI  - Providing services to families of persons with schizophrenia: present and future.
AB  - BACKGROUND: The important role of families and other caregivers in the lives of
      adults with schizophrenia is well documented. Persons with schizophrenia
      frequently live with their families of origin, and the vast majority have regular
      family contact. Families of persons with schizophrenia have also been
      demonstrated to have significant needs. Families most frequently cite the need
      for education and support in helping them to cope with their family member's
      illness. Further, numerous studies have documented the benefits of interventions
      designed to meet the needs of family members. AIMS OF THE STUDY: This paper
      identifies critical issues and challenges in the provision of services to
      families of persons with schizophrenia and other serious and persistent mental
      illnesses. METHODS: This study draws from both a literature review and a summary
      of pertinent data from the Schizophrenia Patient Outcomes Research Team (PORT).
      RESULTS: Recent best practices standards and treatment recommendations specify
      that families should be given education and support. One of the PORT treatment
      recommendations states that "Patients who have on-going contact with their
      families should be offered a family psychosocial intervention which spans at
      least nine months and which provides combinations of: Education about the
      illness; Family support; Crisis intervention; and, Problem solving skills
      training". The PORT treatment recommendations are based on well designed and
      rigorous research on family psychoeducation programs that demonstrate reduced
      relapse rates and improved patient and family well-being for persons whose
      families receive psychoeducation. While family psychoeducation programs have been
      the subject of extensive treatment trials, family members and family
      organizations have endorsed a variety of other models of services such as family
      education and consultation models. These models have not been as rigorously
      researched as family psychoeducation. Control groups are generally lacking. No
      consistent findings have been reported, although isolated studies have found
      increased knowledge, self-efficacy and greater satisfaction with treatment among
      families who have participated in family education programs. Remarkably little is
      known about the extent to which families actually receive appropriate services.
      However, PORT data from administrative claims and client interviews suggest that
      family services are minimal. Further, previous research has consistently revealed
      that families have high levels of dissatisfaction with mental health services
      DISCUSSION: If family psychoeducation is effective, why do all the data suggest
      that it is scarcely offered? Even use of family education programs, which are
      perhaps easier to deliver and cheapter, is limited. Some answers to these
      questions may be found in evaluations of efforts to disseminate family education
      and psychoeducation models. The Schizophrenia PORT sponsored a dissemination of
      William McFarlane's multiple family psychoeducational group. One obstacle to
      implementation was lack of programmatic leadership at agencies. Another was
      conflict between the philosophy and principles of the family model and typical
      agency practices. Dissemination efforts of the MFPG model are under way in the
      states of Illinois and Maine. IMPLICATIONS FOR FURTHER RESEARCH: Four main areas
      of research are necessary to achieve progress in providing services to families
      and persons with serious and persistent brain diseases such as schizophrenia. (i)
      We need a better understanding of the current state of affairs, including
      systematic exploration of what kinds of service different kinds of family are
      receiving or not receiving and from whom. Research on treated populations is not
      sufficient. Billing records alone will not account for the informal
      clinician/family contacts, which are valued. This research must include the
      patient, family and clinician perspectives as well as incorporating systemic
      factors such as financing and organization of services. (ii) A second area of
      research should focus on family interventions. What works for whom and at what
      cost? What are the critical ingredients of successful family models? Peer-led
      community family education programs are severely under-researched. While
      psychoeducation has established efficacy, it may have maximal value in first
      break patients. How can the acceptability of psychoeducation to families and
      clinicians be maximized? Are there ways to capitalize on the best of clinician
      run and family-run models to create hybrid models? Does family psychoeducation
      shift costs toward or away from families? (iii) How can successful family
      services models be disseminated effectively? Although it is still necessary to
      know more about the current status of services to families, it is quite clear
      that the best researched psychoeducation programs have limited, if any,
      penetration in typical communities. Approaches that combine grassroots
      participation of clinicians and family members as well as efforts with senior
      administrators and payers are likely to yield the greatest success. (iv) More
      research is necessary on the role of families and other caregivers in recovery
      and course of illness. This research must be driven by an appreciation of the
      biopsychosocial model and be empirical rather than ideological. Such an approach
      will optimally protect families fn5 from their own tendency to self-blame and
      from the tendency of the medical models prevalent in industrialized countries to
      find blame, fault and pathology.

PMID- 11967402
TI  - State-of-the-art challenges for mental health services research.
AB  - BACKGROUND: Research-based, state-of-the-art services for people with serious
      mental disorders would consist of demonstrably effective treatments, organized
      synergistically, and financed in ways that create incentives to provide such
      treatment. While research exists in these domains of treatment, organization and
      financing, this research base contains significant gaps, and what is known
      frequently neither informs policy making nor enters practice. REVIEW: The NIMH
      services-research portfolio has identified successful patient-level and system
      level interventions for people with serious mental disorders, but much of this
      research has yet to make its way into practice. Similarly, while we have made
      progress in asking "what is good care?", we have much less information about the
      answers to "what constitutes an adequate try?". Writing a prescription for an
      efficacious medication does not constitute an adequate trial of that medication.
      Similarly, offering people boring psychosocial rehabilitation programs does not
      constitute an adequate try of promoting recovery via rehabilitation services, but
      what does? Defining what constitutes an adequate try can be a way of allocating
      scarce resources or it can be a polite way of defining when a system gets to give
      up on someone. As state governments move to contract with managed care entities
      for services for Medicaid beneficiaries, one of the great contracting challenges
      is defining and monitoring the provision of what constitutes an adequate try.
      DISCUSSION: To obtain better value for our health care expenditures, we need to
      find ways to get what we know works into practice, whether we are contracting for
      services or deciding which clinical therapies to pursue. For example, problem
      oriented family therapy has been shown to improve clinical outcomes for people
      with schizophrenia, yet such interventions are rare in practice. We also need to
      pay more attention to the quality of the clinical care actually being delivered -
      not what was prescribed, nor what the clinician was trained in, nor what the job
      description was, but what actually is occurring. Figuring out how to contract for
      and disseminate efficacious treatments so that they occur and are effective in
      real-world settings is critically important yet is a largely unexplored area of
      services research. We need to answer both "what is good care?" and "how do we get
      it to happen?".

PMID- 11967403
TI  - Incorporating economic analysis in evidence-based guidelines for mental health:
      the profile approach.
AB  - BACKGROUND: Many western health systems are currently developing the role of
      clinical guidelines to promote effective and efficient health care. However,
      introducing economic data into guideline methodology designed to assess the
      effectiveness of interventions raises some methodological issues. These include
      providing valid and generalizable cost estimates, the weight placed upon cost
      "evidence" and presenting cost-effectiveness information in a way that is helpful
      to clinicians. AIM OF THE STUDY: To explore a framework for including economic
      concepts in the development of a series of primary care guidelines, two of which
      address mental health conditions. METHODS: A profile approach, setting out best
      available evidence about the attributes of treatment choices (effectiveness,
      tolerability, safety, health service delivery, quality of life, resource use and
      cost), was used to help clinicians to derive treatment recommendations in a
      manner consistent with both the clinical decision-making process and social
      objectives. RESULTS: Clinicians involved in guideline development responded well
      to the process. Although there was often considerable debate about the meaning
      and importance of different aspects of evidence about treatment, in none of the
      guideline groups was there failure to agree treatment recommendations.
      DISCUSSION: The profile approach may be particularly useful in the field of
      mental health where disease processes may often feature very disparate effects,
      over long periods of time and impacting upon a broad circle of relatives, carers
      and agencies in addition to the patients themselves. CONCLUSION: A method has
      been applied in a series of primary care guidelines, which appears to enable
      clinicians to consider the issue of resource use alongside the various clinical
      attributes associated with treatment decisions. The basis of this work is the
      belief that guidance presenting physical measures describing effectiveness,
      adverse events, safety, compliance and quality of life, alongside resource
      consequences, is most likely to appropriately inform doctor-patient interactions.
      IMPLICATIONS FOR HEALTH CARE PROVISON AND USE: This research may provide a useful
      platform for other groups considering how to introduce cost-effectiveness
      concepts into guideline development groups. Whether guidelines change clinical
      behaviour remains a research question, and the subject of forthcoming trials.
      IMPLICATIONS FOR HEALTH POLICY FORMULATION: It is important that government
      agencies realize that guideline development is a health policy tool with
      prescribed methods to produce valid guidelines. Attempts to tamper with the
      methodology for cost-containment purposes or other political reasons are likely
      to discredit a useful mechanism for improving the scientific basis of health care
      provision. IMPLICATIONS FOR FURTHER RESEARCH: There are a number of limitations
      to completed work: for example it has a primary care focus and addresses fairly
      narrowly defined conditions. Work is ongoing to extend the scope to broader
      disease areas and to secondary care.

PMID- 11967404
TI  - Managed behavioral health care and supply-side economics. 1998 Carl Taube
      Lecture.
AB  - BACKGROUND: Within the past decade, the mental health care system in the United
      States has undergone a significant transformation in terms of delivery, financing
      and work force configuration. Contracting between managed care organizations
      (MCOs) and providers has become increasingly prevalent, paralleling the trend in
      health care in general. These managed care carve-outs in behavioral health depend
      on networks of providers who agree to capitated rates or discounted fees for
      service for those patients covered by the carve-out contracts. Moreover, the
      carve-outs use a broader array of mental health providers than is typically found
      in traditional indemnity plans, encourage time-limited versus long-term
      treatments and favor providers who are engaged in outpatient care. This
      phenomenal growth in managed behavioral health care over the past decade includes
      the rapid growth and quick consolidation of mental health MCOs. The period 1992
      1998 shows steady and substantial annual increases in the number of enrollees in
      mental health MCOs, the figure more than doubling from 78.1 million people in
      1992 to a projected 156.6 million in 1998, or 70% of insured lives. Moreover,
      these vast numbers of enrollees are becoming increasingly consolidated into a
      smaller number of firms. In 1997, 12 companies controlled nearly 85% of the
      managed behavioral health care market, with 60% of the market held by the three
      largest firms. STUDY AIMS: This article reviews empirical data and draws policy
      implications from the literature on managed behavioral health care in the United
      States. Starting with spending and spending trend estimates that show the average
      annual growth rate of mental health expenditures to be lower than that of health
      care expenditures in general over the past decade, the author examines
      utilization and price factors that may account for managed-care-induced cost
      reductions in behavioral health care, with special attention to hospital use
      patterns, fee discounting and the supply and earnings patterns of various types
      of mental health provider. In addition, data on staffing ratios and provider
      mixes of health maintenance organizations and mental health MCOs are reviewed as
      they reveal at least part of the dynamics of reconfiguration of the mental health
      work force in this era of managed care. CONCLUSIONS: As measured by changes in
      utilization and price, widespread application of "classic" managed care
      techniques such as preadmission review (gatekeeping), concurrent review, case
      management, standardized clinical guidelines and protocols, volume purchase of
      services and fee discounting appears to have led to significant cost reductions
      for providers of both impatient and outpatient mental health services. However,
      amidst a complex flux of market variables such as risk shifting, changing
      financial incentives and intensity of competition, not all of the reduction or
      slowdown in spending can be clearly and purely attributed to managed care. The
      data on the ongoing reconfiguration of the mental health work force are clearer
      in their implications: with an oversupply of all types of mental health
      providers, managed care has significant potential to increase the incidence of
      provider substitutions and spur the growth of integrated group practices.
      IMPLICATIONS FOR FURTHER RESEARCH: The current body of empirical and policy
      literature in mental health economics suggests several salient areas of follow
      up. Is the proportionately greater impact of managed care on the annual growth
      rate of mental health care spending a temporary phenomenon or does it signal an
      enduring difference in the rates of increase between behavioral health care and
      health care in general? Beyond industry downsizing, what are the substitutions
      among mental health providers that are going on, and will go on, to produce cost
      effective practices? What are the new financial or risk-sharing arrangements
      between providers and MCOs that will produce appropriate and high-quality mental
      health services?

PMID- 11967405
TI  - Economic aspects of mental health carve-outs.
AB  - BACKGROUND: Recent empirical research has found behavioral health carve-outs in
      the US to reduce costs immediately and considerably, compared to indemnity
      insurance and HMOs. Carve-outs have quickly captured a large part of the
      organized market in US behavioral health. At the same time, market concentration
      has increased significantly. METHODS: The current paper uses concepts and results
      from the industrial organization and transaction cost literature to explain (i)
      why carve-outs hold cost advantages over other institutional arrangements, (ii)
      why these hold in particular for behavioral health and (iii) why this did not
      happen earlier. RESULTS: The main explanatory variables relate to economies of
      scale, the avoidance of diseconomies of scope, and the avoidance of personal
      relationships. The sometimes surprising lack of explicit risk-taking by carve
      outs and of explicit cost-reducing incentives in carve-out contracts are more
      than overcome by incentives created from gaining large contracts. The specific
      advantages of carve-outs in behavioral health derive from a combination of lack
      of economies of scope with other health services, lack of economies of scale in
      provision of behavioral health and presence of economies of scale in management.
      It is conjectured that behavioral health carve-outs have benefited from
      biomedical innovations that changed the direction of treatments, from
      computerization that enables large-scale standardized management and from
      financial pressures on the behavioral health sector. DISCUSSION: The empirical
      basis for the current study is a number of case studies and the rapid penetration
      of mental health carve-outs in the US. Cost reductions caused by such carve-outs
      appear to be quite robust. Explaining cost reductions from institutional changes
      has to start with the question of why the old institution did not implement the
      same or similar changes. We have emphasized reasons why such changes were not
      feasible under indemnity insurance and HMOs. Nevertheless, we have not been able
      to evaluate quality changes that might have accompanied those cost reductions.
      IMPLICATIONS FOR HEALTH POLICY: While further cost reductions may follow a
      logistic curve, which simply flattens out, there are developments, regulatory and
      legal in particular, that could lead to a regression of carve-out costs towards
      those under other institutional arrangements. Thus, the main health policy
      questions arising from this study are to what extent the freedom of carve-outs to
      hold costs down should be upheld and to what extent the cost reductions should be
      used to increase behavioral health coverage. IMPLICATIONS FOR FURTHER RESEARCH: I
      see three main avenues for further research. The first is to find more empirical
      evidence for the hypotheses developed in this paper. The second is to look for
      other countries and other areas of health care with characteristics that would
      lend themselves to the application of carve-outs. The third is to analyze the
      quality aspect of carve-outs. The empirical question here is "What has been the
      effect of carve-outs on the quality of behavioral health care in the US?". The
      theoretical question is "What are the incentives of the sponsors of carve-out
      plans and of the carve-out management to assure quality provision of care?".

PMID- 11967407
TI  - Editorial.

PMID- 11967408
TI  - Labor market conditions and employment of the mentally ill.
AB  - BACKGROUND: The mental health services literature includes assertions that
      workers with mental illness are at earlier risk of unemployment than other
      workers when the economy contracts. This possibility is important for several
      reasons. One is that such a phenomenon would support the argument that the lives
      of mentally ill persons are made unnecessarily stressful by the stigma of mental
      illness. Another is that the phenomenon could distort comparisons of the
      effectiveness of programs designed to prepare persons with severe mental illness
      for work. Despite its importance, the assertion that severely mentally ill
      workers are at early risk of unemployment has never been empirically tested. AIMS
      OF THE STUDY: We aim to test the hypothesis that unemployment among persons with
      severe mental illness (SMI) increases before job loss among other workers.
      METHODS: We test the hypothesis by applying Granger causality methods to time
      series data collected in two communities in the United States (i.e., Concord and
      Manchester, NH) over 131 weeks beginning on 12 May 1991. RESULTS: We find no
      relationship between job loss in the labor market and the likelihood that persons
      with SMI will be unemployed. DISCUSSION: We speculate that persons with SMI
      participate in the secondary labor market and that their employment status is
      unlikely to be well described by data gathered in the primary labor market. This
      implies that widely available measures of labor market status, which are designed
      to describe the primary labor market, cannot be used to improve the evaluation of
      programs intended to prepare the mentally ill for work. We also discuss the
      possibility that persons with SMI may have needs that are better met by the
      secondary than by the primary labor market. CONCLUSIONS: The intuition that
      workers with severe mental illness are affected earlier than other workers by
      labor market contraction may not be correct. We infer that persons with severe
      mental illness may participate in the secondary labor market about which we know
      relatively little. We cannot, therefore, easily adjust program evaluations to
      disentangle intervention effects from those, if any, of the labor market.

PMID- 11967409
TI  - Willingness to pay as a measure of the benefits of mental health care.
AB  - BACKGROUND: Decision-makers would benefit from being able to plan and evaluate
      mental health care interventions or programmes on the basis of costs and
      consequences that are measured in the same unit of measurement (money being the
      most convenient). Monetized quantification of the consequences of alternative
      interventions could be subsequently incorporated into cost-benefit allocation
      decisions. AIM: This paper provides an overview of the policy and research
      context within which willingness-to-pay survey techniques are located, together
      with a review of the main approaches used to date. We also highlight key issues
      in the application of these techniques and indicate areas of mental health
      research and policy that could benefit from their introduction. METHOD:
      Willingness-to-pay survey techniques are reviewed, and issues concerning their
      validity and application in the context of cost-benefit analyses of mental health
      policies are discussed. DISCUSSION: Different survey methods are available for
      generating willingness-to-pay data, the most common being the contingent
      valuation approach. An assessment of the validity of data generated by these
      alternative techniques is vital in order to ensure that they are consistent with
      the notion of economic preferences and values. IMPLICATIONS: The generation of
      valid and meaningful data on the monetized value of mental health outcomes would
      provide decision-makers with an improved evidence-based framework for resource
      allocation.

PMID- 11967410
TI  - The productivity of mental health care: an instrumental variable approach.
AB  - BACKGROUND: Like many other medical technologies and treatments, there is a lack
      of reliable evidence on treatment effectiveness of mental health care.
      Increasingly, data from non-experimental settings are being used to study the
      effect of treatment. However, as in a number of studies using non-experimental
      data, a simple regression of outcome on treatment shows a puzzling negative and
      significant impact of mental health care on the improvement of mental health
      status, even after including a large number of potential control variables. The
      central problem in interpreting evidence from real-world or non-experimental
      settings is, therefore, the potential "selection bias" problem in observational
      data set. In other words, the choice/quantity of mental health care may be
      correlated with other variables, particularly unobserved variables, that
      influence outcome and this may lead to a bias in the estimate of the effect of
      care in conventional models. AIMS OF THE STUDY: This paper addresses the issue of
      estimating treatment effects using an observational data set. The information in
      a mental health data set obtained from two waves of data in Puerto Rico is
      explored. The results using conventional models - in which the potential
      selection bias is not controlled - and that from instrumental variable (IV)
      models - which is what was proposed in this study to correct for the contaminated
      estimation from conventional models - are compared. METHODS: Treatment
      effectiveness is estimated in a production function framework. Effectiveness is
      measured as the improvement in mental health status. To control for the potential
      selection bias problem, IV approaches are employed. The essence of the IV method
      is to use one or more instruments, which are observable factors that influence
      treatment but do not directly affect patient outcomes, to isolate the effect of
      treatment variation that is independent of unobserved patient characteristics.
      The data used in this study are the first (1992-1993) and second (1993-1994) wave
      of the ongoing longitudinal study Mental Health Care Utilization Among Puerto
      Ricans, which includes information for an island-wide probability sample of over
      3000 adults living in poor areas of Puerto Rico. The instrumental variables
      employed in this study are travel distance and health insurance sources. RESULTS:
      It is very noticeable that in this study, treatment effects were found to be
      negative in all conventional models (in some cases, highly significant). However,
      after the IV method was applied, the estimated marginal effects of treatment
      became positive. Sensitivity analysis partly supports this conclusion. According
      to the IV estimation results, treatment is productive for the group in most need
      of mental health care. However, estimations do not find strong enough evidence to
      demonstrate treatment effects on other groups with less or no need. The results
      in this paper also suggest an important impact of the following factors on the
      probability of improvement in mental health status: baseline mental health
      status, previous treatment, sex, marital status and education. DISCUSSION: The IV
      approach provides a practical way to reduce the selection bias due to the
      confounding of treatment with unmeasured variables. The limitation of this study
      is that the instruments explored did not perform well enough in some IV
      equations, therefore the predictive power remains questionable. The most
      challenging part of applying the IV approach is on finding "good" instruments
      which influence the choice/quantity of treatment yet do not introduce further
      bias by being directly correlated with treatment outcome. CONCLUSIONS: The
      results in this paper are supportive of the concerns on the credibility of
      evaluation results using observation data set when the endogeneity of the
      treatment variable is not controlled. Unobserved factors contribute to the
      downward bias in the conventional models. The IV approach is shown to be an
      appropriate method to reduce the selection bias for the group in most need for
      mental health care, which is also the group of most policy and treatment concern.
      IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The results of this work have
      implications for resource allocation in mental health care. Evidence is found
      that mental health care provided in Puerto Rico is productive, and is most
      helpful for persons in most need for mental health care. According to what
      estimated from the IV models, on the margin, receiving formal mental health care
      significantly increases the probability of obtaining a better mental health
      outcome by 19.2%, and one unit increase in formal treatment increased the
      probability of becoming healthier by 6.2% to 8.4%. Consistent with other mental
      health literature, an individual's baseline mental health status is found to be
      significantly related to the probability of improvement in mental health status:
      individuals with previous treatment history are less likely to improve. Among
      demographic factors included in the production function, being female, married,
      and high education were found to contribute to a higher probability of
      improvement. IMPLICATION FOR FURTHER RESEARCH: In order to provide accurate
      evidence of treatment effectiveness of medical technologies to support decision
      making, it is important that the selection bias be controlled as rigorously as
      possible when using information from a non-experimental setting. More data and a
      longer panel are also needed to provide more valid evidence. tion.

PMID- 11967411
TI  - The need for mental health services research focusing on poor young women.
AB  - Despite the fact that the relationship between poverty and increased risk for a
      broad spectrum of mental disorders has been documented for several decades, very
      little is known about providing mental health treatments to poor individuals. In
      this paper, we emphasize the importance of developing, and empirically
      evaluating, sensitive and appropriate interventions for poor young women who
      suffer from common mental disorders. WHO ARE THE US POOR?: In the US, nearly 14%
      of individuals live in poverty, and another 20% in near poverty. The poor are
      disproportionally women and children such that 63% of female-headed households
      are poor. Young women and ethnic minorities are over-represented among the poor
      also, with 55% of those living below the poverty level being minorities. NEEDS
      AND BARRIERS TO CARE AMONG POOR, YOUNG WOMEN: The poor have more mental disorders
      than those with more resources. Further, women are twice as likely as men to have
      a mood or anxiety disorder, including major depression and post-traumatic stress
      disorder (PTSD), with younger women at higher risk than older women. Research
      alos indicates that poor women have high exposure to traumatic events and
      cumulative adversity that is directly related to their mental health. This
      history may serve, in part, as a barrier to seeking mental health care. Other
      barriers in this population include lack of insurance, lack of access to primary
      care where mental disorders might be detected, practical problems like lack of
      childcare or transportation, and the inflexibility of low-income service jobs.
      Religious beliefs and attitudes about mental health treatment may play a role as
      well. Recent policy changes in the US have contributed to the vulnerability of
      this group as eligibility for welfare programs has reduced, and time limits have
      decreasd. Services for immigrants are also severely limited, and managed care
      strategies for those in the public sector may be confusing. IMPORTANT, UNANSWERED
      QUESTION: More needs to be learned about the mental health status and needs of
      poor women, along with the impact of loss of public support on their physical and
      mental health. Access to mental health care within a managed care setting also
      needs to be addressed, and care taken to understand the particular needs of poor
      populations that will actually make these services accessible to them.
      Insufficient attention has thus far been paid to the cost implications of
      providing these services to the poor. While providing treatment is associated
      with significant costs, the costs of not providing care, especially the effects
      of depression on offspring, should not be overlooked. CHALLENGES TO EXAMINING
      MENTAL HEALTH IN POOR WOMEN: A number of suggestions were made for addressing
      practical and methodological challenges to providing mental health services.
      These include placing services for these individuals within their familiar
      medical settings, which requires close working relationships between psychiatric
      and medical personnel within these settings. Outreach is a necessary part of
      getting poor women into treatment, and should be a routine part of helping women
      become engaged with caregivers. Providing culturally sensitive treatments is an
      important focus too, through developing knowledge about the culturally based
      customs and expectations of target groups. Measurement issues need to be attended
      to, as most research instruments have been developed on middle class populations,
      and have not been examined for their psychometric properties and norms in less
      advantaged groups. Careful translation techniques are also required. Finally,
      working with institutions sponsoring research to educate them about special
      problems and challenges with these groups will help improve the quality and
      efficiency of the work accomplished.

PMID- 11967412
TI  - Improving research on primary care patients with mental health problems:
      observations from an investigator.
AB  - BACKGROUND AND AIMS OF THE MANUSCRIPT: The purpose of this manuscript is to
      define under-recognized perspectives that the primary care research field needs
      to integrate into research initiatives, and to discuss practical strategies to
      ensure the successful implementation of these initiatives. METHODS: Perspectives
      and strategies were identified through personal experience, informal discussion
      with ten senior investigators in the field and a selected literature review.
      RESULTS: Research on improving treatment for the mental health problems of
      primary care patients will progress more rapidly if investigators explore the
      usefulness of a competing demands framework, integrate a readiness to change
      perspective in developing more individualized interventions for providers and
      patients, evaluate interventions for their effect on productivity and test
      alternative interventions particularly in patients who fail to benefit from
      currently accepted treatment. The implementation of these initiatives will be
      more successful if research teams define unique scientific agendas, invest energy
      in pursuing questions whose value is undisputed by multiple parties, increase the
      rate of inter-institutional exchange between senior and junior investigators,
      pilot test assumptions that affect project budget and timeline, build in a
      limited amount of slack time in early phases of project implementation and
      network effectively. IMPLICATIONS FOR FURTHER RESEARCH: Investigator efforts to
      define critical questions for the primary care management of mental health
      problems will be enhanced if they revisit the definition of their research
      agendas in the light of new perspectives that are emerging in the field.
      Similarly, the implementation of these agendas will be strengthened if
      investigators make conscious attempts to use one or more of the strategies
      suggested.

PMID- 11967413
TI  - Comments upon "improving research on primary care patients with mental health
      problems"

PMID- 11967416
TI  - Editorial.

PMID- 11967414
TI  - Information needs for community practice: responding to the challenge.

PMID- 11967417
TI  - Rational decision-making in mental health: the role of systematic reviews.
AB  - BACKGROUND: "Systematic reviews" have come to be recognized as the most rigorous
      method of summarizing confusing and often contradictory primary research in a
      transparent and reproducible manner. Their greatest impact has been in the
      summarization of epidemiological literature - particularly that relating to
      clinical effectiveness. Systematic reviews also have a potential to inform
      rational decision-making in healthcare policy and to form a component of economic
      evaluation. AIMS OF THE STUDY: This article aims to introduce the rationale
      behind systematic reviews and, using examples from mental health, to introduce
      the strengths and limitations of systematic reviews, particularly in informing
      mental health policy and economic evaluation. METHODS: Examples are selected from
      recent controversies surrounding the introduction of new psychiatric drugs (anti
      depressants and anti-schizophrenia drugs) and methods of delivering psychiatric
      care in the community (case management and assertive community treatment). The
      potential for systematic reviews to (i) produce best estimates of clinical
      efficacy and effectiveness, (ii) aid economic evaluation and policy decision
      making and (iii) highlight gaps in the primary research knowledge base are
      discussed. Lastly examples are selected from outside mental health to show how
      systematic reviews have a potential to be explicitly used in economic and health
      policy evaluation. RESULTS: Systematic reviews produce the best estimates of
      clinical efficacy, which can form an important component of economic evaluation.
      Importantly, serious methodological flaws and areas of uncertainty in the primary
      research literature are identified within an explicit framework. Summary indices
      of clinical effectiveness can be produced, but it is difficult to produce such
      summary indices of cost effectiveness by pooling economic data from primary
      studies. Modelling is commonly used in economic and policy evaluation. Here,
      systematic reviews can provide the best estimates of effectiveness and,
      importantly, highlight areas of uncertainty that can be used in "sensitivity
      analysis". DISCUSSION: Systematic reviews are an important recent methodological
      advance, the potential for which has only begun to be realized in mental health.
      This use of systematic reviews is probably most advanced in producing critical
      summaries of clinical effectiveness data. Systematic reviews cannot produce valid
      and believable conclusions when the primary research literature is of poor
      quality. An important function of systematic reviews will be in highlighting this
      poor quality research which is of little use in mental health decision making.
      IMPLICATIONS FOR HEALTH PROVISION: Health care provision should be both
      clinically and cost effective. Systematic reviews are a key component in ensuring
      that this goal is achieved. IMPLICATIONS FOR HEALTH POLICIES: Systematic reviews
      have potential to inform health policy. Examples presented show that health
      policy is often made without due consideration of the research evidence.
      Systematic reviews can provide robust and believable answers, which can help
      inform rational decision-making. Importantly, systematic reviews can highlight
      the need for important primary research and can inform the design of this
      research such that it provides answers that will help in forming healthcare
      policy. IMPLICATIONS FOR FURTHER RESEARCH: Systematic reviews should precede
      costly (and often unnecessary) primary research. Many areas of health policy and
      practice have yet to be evaluated using systematic review methodology. Methods
      for the summarization of economic data are methodologically complex and deserve
      further research

PMID- 11967418
TI  - New research alliances in the era of managed care.
AB  - BACKGROUND: The rise of managed behavioral health care in the United States was
      accompanied by reductions in costs, which has shifted the policy debate from
      concerns about rising costs to questions of universal access, mental health
      benefits at parity with medical benefits and quality of care. To meet these new
      challenges, managed care organizations, the purchasers of health care and
      academic services researchers must work together in new ways. AIMS OF THE STUDY:
      This paper discusses collaborative efforts between a for-profit managed care
      firm, academia and purchasers of health care coverage to study parity for mental
      health and substance abuse and how this effort has become part of a research
      strategy to inform policy. Historical, strategic and methodological issues are
      presented. METHODS: Case Study. RESULTS: Although the benefits from cooperative
      research are substantial, there are severe hurdles. Managed care organizations
      often have data that could answer pressing policy questions, yet these data are
      rarely used by researchers because it is difficult to obtain access and because
      analyzing the data requires computing facilities and skills that are not common
      in health services research. In turn, managed care organizations can learn how to
      design and implement more informative data systems that eventually lead to more
      cost-effective care, but there often are more immediately pressing business
      considerations and sometimes resistance to outside scrutiny. Important features
      that made this cooperation successful include strong support from the senior
      management in the company, including complete access to their extensive
      databases, and established funding for a managed care research center by the
      National Institute of Mental Health. CONCLUSION: This paper illustrates the
      potential of collaborative research. New research challenges, such as the
      linkages between quality and cost-effectiveness in actual practice settings, can
      only be met successfully if we build alliances among payors, managed care
      companies and academic researchers.

PMID- 11967419
TI  - Measuring costs of guideline-driven mental health care: the Texas Medication
      Algorithm Project.
AB  - BACKGROUND: Algorithms describe clinical choices to treat a specific disorder. To
      many, algorithms serve as important tools helping practitioners make informed
      choices about how best to treat patients, achieving better outcomes more quickly
      and at a lower cost. Appearing as flow charts and decision trees, algorithms are
      developed during consensus conferences by leading experts who explore the latest
      scientific evidence to describe optimal treatment for each disorder. Despite a
      focus on "optimal" care, there has been little discussion in the literature
      concerning how costs should be defined and measured in the context of algorithm
      based practices. AIMS OF THE STUDY: This paper describes the strategy to measure
      costs for the Texas Medication Algorithm project, or TMAP. Launched by the Texas
      Department of Mental Health and Mental Retardation and the University of Texas
      Southwestern Medical Center at Dallas, this multi-site study investigates
      outcomes and costs of medication algorithms for bipolar disorder, schizophrenia
      and depression. METHODS: To balance costs with outcomes, we turned to cost
      effectiveness analyses as a framework to define and measure costs. Alternative
      strategies (cost-benefit, cost-utility, cost-of-illness) were inappropriate since
      algorithms are not intended to guide resource allocation across different
      diseases or between health- and non-health-related commodities. "Costs" are
      operationalized consistent with the framework presented by the United States
      Public Health Service Panel on Cost Effectiveness in Medicine. Patient specific
      costs are calculated by multiplying patient units of use by a unit cost, and
      summing over all service categories. Outpatient services are counted by
      procedures. Inpatient services are counted by days classified into diagnosis
      groups. Utilization information is derived from patient self-reports, medical
      charts and administrative file sources. Unit costs are computed by payer source.
      Finally, hierarchical modeling is used to describe how costs and effectiveness
      differ between algorithm-based and treatment-as-usual practices. DISCUSSION: Cost
      estimates of algorithm-based practices should (i) measure opportunity costs, (ii)
      employ structured data collection methods, (iii) profile patient use of both
      mental health and general medical providers and (iv) reflect costs by payer
      status in different economic environments. IMPLICATION FOR HEALTH CARE PROVISION
      AND USE: Algorithms may help guide clinicians, their patients and third party
      payers to rely on the latest scientific evidence to make treatment choices that
      balance costs with outcomes. IMPLICATION FOR HEALTH POLICIES: Planners should
      consider consumer wants and economic costs when developing and testing new
      clinical algorithms. IMPLICATIONS FOR FURTHER RESEARCH: Future studies may wish
      to consider similar methods to estimate costs in evaluating algorithm-based
      practices.

PMID- 11967420
TI  - Prevalence and patterns of major depressive disorder in the United States labor
      force.
AB  - BACKGROUND AND AIMS OF THE STUDY: In this paper, we identify the 12-month and
      lifetime prevalence of major depressive disorder in and out of the labor force,
      and among the employed and unemployed. We examine whether prevalence by labor
      force and employment status varies by gender and over the life cycle. Finally, we
      examine whether people can "recover" from depression with time by identifying
      patterns of labor force participation and employment as time since most recent
      episode passes. METHODS: We examine data collected as part of the National
      Comorbidity Survey, a survey representative of the population of the United
      States designed to identify the prevalence of major mental illnesses. The
      National Comorbidity Study identified cases of major depression via the Composite
      International Diagnostic Interview. Using these data, we estimate univariate and
      bivariate frequency distributions of major depressive disorder. We also estimate
      a set of multivariate models to identify the effect of a variety of dimensions of
      major depression on the propensity to participate in the labor force, and be
      employed if participating. RESULTS: Lifetime and 12-month prevalence rates of
      depression are similar in and out of the labor force. Within the labor force,
      however, depression is strongly associated with unemployment. The negative
      relationship between depressive disorder and employment is particularly strong
      for middle age workers. Depression and the number of depressive episodes have a
      differing pattern of effects on labor market outcomes for men and women. We find
      evidence that labor force participation and employment rates for people with a
      history of depression increase significantly over time in the absence of
      additional depressive episodes. DISCUSSION: Labor market status represents an
      important dimension along which prevalence of major depression varies. The
      relationship between depression and employment status is particularly strong for
      middle aged persons, but becomes weaker as time passes since the last depressive
      episode. Continued exploration of the association between work (or lack of work)
      and depression may ultimately help in the prediction, treatment and assessment of
      the illness. IMPLICASIONS FOR PRACTICE AND POLICY: These results present a basic
      set of facts about the relationship between major depressive disorder and labor
      market outcomes. We have not, however, attempted to sort out the complexities of
      this relationship here. These complexities arise at almost every turn. For
      instance, the high level of prevalence of depression among the unemployed may be
      due to the possibility that the stresses associated with unemployment trigger
      depressive episodes or to the possibility that workers who are depressed are more
      likely to be fired or quit. IMPLICATIONS FOR FURTHER RESEARCH: Our continuing
      research attempts to address these problems. Understanding when and how
      depression affects labor market outcomes and when and how labor market outcomes
      affect depression is an important endeavor for those interested in treating the
      disease and understanding its consequences.

PMID- 11967421
TI  - Costs of drug abuse to society.
AB  - BACKGROUND: The costs of substance abuse in the USA are enormous and varied.
      Seldom are they comprehensively assessed. A new study jointly published by the
      National Institute on Drug Abuse (NIDA) and the National Institute on Alcoholism
      and Alcohol Abuse (NIAAA) has done just this. AIMS: Researchers for the economic
      cost of alcohol and drug abuse in the United States, 1992 used systematic cost-of
      illness measurement methods to evaluate the burden drug abuse and dependency
      place on the US economy. This burden includes widespread disability, morbidity,
      premature death, and diversion of economic resources to drug-related activities.
      Conceptualizing, identifying, and measuring this burden was a major undertaking;
      the report describes the methods in detail. METHOD: Costs are measured as the
      value of resources used (direct costs) or lost during a one year period. As
      adopted here, the human capital approach estimates an individual's value to
      society in terms of his or her production potential. The value of future lost
      earnings is discounted to present time. Finally, the study adopts a societal
      point of view that is consistent with the recommendations of the Panel on Cost
      Effectiveness in Health and Medicine that was convened by the U.S. Public Health
      Service in 1993. Therefore, this study considers all health and non-health
      outcomes and costs created by drug abuse and dependency for the entire
      population. RESULTS: For drug abuse, the annual cost in 1992 is estimated at $98
      billion. By 1995, this estimate rose to $110 billion after adjusting for
      inflation and population change. For 1988, a previous and similar study estimated
      a cost of $58 billion. The distribution of costs is of particular concern.

PMID- 11967423
TI  - How to get the information needed to inform decision-makers - an economic
      perspective.
AB  - From an economic viewpoint, the amount of primary research conducted on a topic
      at any given point in time depends on grantmaker and researcher incentives. The
      potential addresses of research findings often set these incentives. Following
      this logic, there is an economic explanation provided for the availability of
      primary data in effcacy studies. This also explains the lack of data in other
      important fields of health care. This article evaluates why there are few studies
      on effectiveness and cost-effectiveness then discusses how research incentives
      might be changed to overcome this problem. As a result of cost containment
      efforts in some countries, this process has already been initialized.

PMID- 11967422
TI  - Commentary: The benefits of collaboration in research: who will pay?
AB  - Collaboration between MCOs and researchers holds promise for benefiting consumers
      by working on quality-of-care-related research. There are at least three areas of
      collaboration that might benefit both researchers and MCOs: (1) the developing
      and validating of management and fiscal indicators, (2) developing and validating
      clinical indicators and (3) studying access to treatment for vulnerable
      populations. These three areas offer benefits to the MCO and unusual research
      opportunities for investigators. Barriers for both MCOs and researchers must be
      overcome before this work can be carried out, not the least of which is who will
      pay for the work to be done.

PMID- 11967425
TI  - Editorial.

PMID- 11967424
TI  - What type of information is needed to inform mental health policy?
AB  - The most valuable research integrates from thre levels of investigation: clinical
      efficacy, "real life" effectiveness (including cost-effectiveness) and policy
      research. Successful applications of systematic reviews have largely been limited
      to clinical efficacy questions. The contribution of systematic reviews/meta
      analyses to effectiveness and economic questions in mental health has been very
      minor and their contribution to inform policy is negligible. The latter is
      unlikely to change due to the different type of information that policy makers
      need.

PMID- 11967426
TI  - Organizational determinants of psychosocial treatment activity of providers in Va
      mental health facilities.
AB  - OBJECTIVE: To identify the determinants of level and intensity of psychosocial
      treatment activity among staff who deliver services to the severely and mentally
      ill. METHODS: The study sample consisted of 769 treatment providers working in 77
      units in 29 VA mental health facilities. Level of psychosocial care was measured
      as the number of patient contacts and total hours spent in psychosocial care over
      a 1 week period. Intensity of psychosocial care was measured as the average time
      per patient contact. We used hierarchical linear modeling (HLM) to examine the
      association between level and intensity of care and three categories of
      determinants - individual provider attributes, work characteristics and treatment
      setting characteristics. RESULTS: Providers' occupation is related to both the
      level and intensity of care. Providers with administrative responsibilities also
      have fewer patient contacts and lower intensity of such contacts. Providers who
      perceived their pay and benefits more positively had fewer patient contacts and
      less intensive patient contacts. Positive relationships with patients and
      providers were also associated with greater levels and intensity of psychosocial
      treatment activity among providers. Finally, statistically significant
      differences in psychosocial treatment activity among units were identified
      although such differences are not attributable to unit size, patient cohort
      severity or unit workload. CONCLUSIONS: Level and intensity of psychosocial
      treatment activity vary systematically by individual attributes of providers,
      characteristics of the work they perform and attributes of the treatment setting.
      These factors may provide the basis for designing interventions to modify
      provider behavior in a manner consistent with emerging financial pressures and
      treatment modalities for the seriously mentally ill.

PMID- 11967427
TI  - Economic evaluation and mental health: sparse past. fertile future?
AB  - BACKGROUND: Demands for economic inputs to mental health policy-making, practice
      decisions and research evaluations have grown considerably in recent years, but
      the overall supply response has been modest and uneven. AIMS: This paper examines
      the key historical phases in the development of mental health economics research,
      and what they imply for the way economics is received and employed. Focusing on
      the quest for cost-effectiveness, the paper considers challenges for mental
      health economics. METHODS: An informal review of the growing demand for mental
      health economics (and how that demand has been expressed), and how economists
      have responded. RESULTS: Five historical development phases characterize this
      growth. Initially, the dominant feature is innocence or neglect of scarcity. Cost
      measures are rarely calculated, cost-effectiveness is not part of the decision
      making lexicon and the potential for inefficiency is huge. In the second phase,
      innocence turns to criticism of attempts to introduce resource rationality, and
      many clinicians actively reject economics. Health is seen as priceless, and not
      to be compromised by the pursuit of efficiency. After a period of reluctance
      there follows impetuosity as the need for economic insights is recognized, but
      the search for data is desperate and undiscriminating. Poor quality research is
      conducted, with the risk that decisions are misinformed and perhaps damaging.
      Once again, resources are inappropriately used. Next follows the constructive
      development phase: previous mistakes are appreciated and the standards of
      evaluation improve markedly. Studies are better designed, more likely to be
      integrated into clinical or policy evaluations, carefully conducted and sensibly
      interpreted. Inefficiency should be reduced, along with inequity. Finally, there
      is perhaps a nirvana-like fifth phase in which sophisticated economic studies are
      widely undertaken, where systematic reviews and meta-analyses help to reveal the
      wider picture and where findings are readily available to clinicians, managers
      and providers. Whether such a stage is attainable is open to question.
      DISCUSSION: Although the number and sophistication of economic evaluations have
      both increased noticeably over recent years, there remain imbalances. There is
      little economics evidence on care arrangements or treatments for dementia, most
      of the neuroses and the disorders of childhood and adolescence. There are many
      fewer good evaluations of psychological interventions than of drug treatments.
      Geographically, few economic evaluations are conducted outside Western Europe,
      North America or Australasia. IMPLICATIONS FOR DECISION-MAKERS AND RESEARCH: Many
      challenges consequently face the next generation of mental health economics
      evaluations, both for research economists and for those health care decision
      makers who find themselves increasingly having to draw on economics evidence. One
      challenge is to be fully aware that the information that economists can currently
      offer may fall short of what decision-makers need. The gap between the two must
      be fully appreciated. Building more comprehensive pictures of the cost and
      outcome consequences of different care policies and treatment interventions is
      one way to bridge this gap. At the same time a sense of perspective must be
      maintained and promoted. For example, there is growing concern across the world
      about the high prices of new drugs, yet drug acquisition costs usually represent
      only a small proportion of total costs. Decisions sometimes appear to be
      disproportionately focused on small parts of the overall mental health care
      picture. A similar tendency prompts another challenge, which is to undertake and
      interpret research so as to overcome, or at least not to exacerbate, the boundary
      problems that characterize the multi-service, multi-agency reality of many mental
      health care systems. The adequacy of short-term evaluations - which dominate our
      field - must be questioned in light of the chronicity of many mental health
      problems, and of their externality effects (including inter-generational
      transmission of problems). Although funding will always be a problem, longer-term
      evidence is needed. So, too, is research that looks at the reasons for inter
      individual cost and outcome variations. Economic evaluations should also pay more
      attention to equity as well as efficiency as a criterion of improved resource
      allocation. Finally, more economic data should be gathered alongside and not
      after clinical data, particularly as economic assumptions often appear to drive
      key practice and policy changes.

PMID- 11967428
TI  - The mental health care delivery system in greece: regional variation and
      socioeconomic correlates.
AB  - BACKGROUND: In Greece, the functional capacity of the mental health care system
      until 1980, was totally inadequate to meet the increasing mental health needs of
      the population and to provide efficient and community-based services. This
      situation was brought to the attention of the Commission of European Communities
      and a special EEC Regulation No 815/84 provided the financial technical support
      for an extended psychiatric reform programme. The psychiatric reform programme
      initiated in 1984 and ended in 1995. AIMS OF THE STUDY: This study compared the
      geographical distribution of neuropsychiatrists and the mental health care
      delivery system structural components (psychiatric beds, extramural mental health
      units and places in rehabilitation services), according to the regional
      socioeconomic development for the years 1984, 1990 and 1996. Additionally the
      possible effects of the operation of community-based mental health services on
      the psychiatric hospitalizations were examined. METHODS: Data on the geographical
      distribution of neuropsychiatrists in the previously mentioned years were drawn
      from local Medical Association from each of 54 prefectures of the country. The
      corresponding distribution of the mental health care delivery system components
      was made available from the database of the Monitoring and Evaluation of Mental
      Health Services Unit. Pearson product moment correlations of the regional
      distribution of neuropsychiatrists and the various components of the mental
      health care system, as population-based ratios, with the corresponding
      socioeconomic development in the form of the general index of development were
      performed. Mental hospital age standardized rates were collected from the
      Hospital Central Register for the periods 1984-1987 and 1990-1993. Discharge
      rates were elaborated according to the existence of mental health services in
      specific regions. RESULTS: A wide regional variation in neuropsychiatrists per
      100000 population was found in all three years, with the majority of them working
      in the greater Athens and Thessaloniki areas. In the geographical distribution of
      health regions, there is an uneven significant decrease in psychiatric beds
      between 1984 and 1996. However in almost all regions an increase in extramural
      services between the two critical periods was noticed, as part of the
      implementation of the psychiatric reform programme. A parallel and more dramatic
      increase in the places of rehabilitation in 12 out of 13 regions has been
      observed during the implementation of the reform programme. At the level of
      prefectures, the changes across time, in the mean ratios of beds, extramural
      services and rehabilitation places were not found to be significant. A
      significant decrease of discharges in prefectures covered by newly established
      extramural services for the period 1990-1993, compared to discharge rates during
      the period 1984-1987, when none of these services were in operation in these
      prefectures, was noticed. The intercorrelation matrix between the various mean
      values (1990-1996) of the mental health care system components in the 54
      prefectures and the local general index of development scores produced
      statistically significant correlation coefficients. It seems that the greater the
      level of local socioeconomic development the higher the degree of mental health
      care delivery system growth. DISCUSSION: Our results have shown uneven regional
      distribution of neuropsychiatrists, as well as extramural mental health units and
      rehabilitation places, despite the current reorganization of the whole mental
      health care delivery system. The positive correlation between the various
      structural components of the system in the 54 prefectures and the local
      socioeconomic conditions could be interpreted as follows. Urban areas of higher
      socioeconomic growth had a long history of development of inpatient services in
      mental hospitals. In these several community-based alternatives have been
      established for their transformation into modern ones. Urban areas exhibit also
      higher psychiatric morbidity and therefore increasing mental health needs.
      Additionally in several cities local University Psychiatric Departments have
      developed a variety of mental health and rehabilitation services. Many new
      services highly specialized and complementary to existing mental hospitals were
      established in urban areas. Rural areas are mostly uncovered by mental health
      care facilities. However it seems that the establishment of community-based
      services could have an effect on mental hospital utilization. CONCLUSION: It
      becomes evident that after the implementation of the psychiatric reform programme
      in Greece significant progress in the areas of decentralization of mental health
      and rehabilitation services has been observed. However there are still areas in
      many prefectures, mainly rural or semirural, lacking the appropriate delivery of
      mental health care. IMPLICATIONS FOR HEALTH CARE AND POLICY FORMULATION: Our
      results suggest that flexible models of services should be introduced for the
      benefit of population living in areas lacking the necessary socioeconomic
      resourses. IMPLICATIONS FOR FUTURE RESEARCH: Mental health services research in
      Greece should focus on quasi-experimental studies on the effectiveness of various
      models of mental health care in areas of different socioeconomic growth.

PMID- 11967429
TI  - Identifying factors affecting the placement of mentally ill patients.
AB  - BACKGROUND: There is now general agreement that a comprehensive psychiatric
      service can operate with the minimum use of in-patient facilities. Consequently,
      the emphasis in most European countries is on reducing the number of inpatient
      beds and expanding the range of community care facilities, including day hospital
      services, available to mentally ill patients. Decision-making with respect to
      placement is now even more important given the changes currently taking place on
      the supply side. METHOD: The study examines the factors that influence placement
      decision-making between inpatient care and day hospital care in one Health Board
      in Ireland. Placement was examined over a 9 month period for all patients
      presenting for treatment in one particular area with a population of 39000
      people. Patients were not randomized between the two settings due to ethical
      concerns about the randomization process. The issue of placement is analysed
      using a logit estimation procedure. RESULTS: The results suggest that two
      variables have a significant affect on placement for the population under review:
      whether the patient is accompanied at the time of admission and the domicile of
      the patient. CONCLUSIONS: Greater flexibility with respect to the opening hours
      of day hospital facilities, linked to improved transport facilities, together
      with further analysis on the process of admission to hospital, particularly the
      dynamics of the interaction between providers, patients, and accompanying
      persons, may improve placement decision-making for mentally ill patients.

PMID- 11967430
TI  - The labor market consequences of family illness.
AB  - BACKGROUND: This study examines the impact of mental illness on the labor market
      performance of family members of afflicted individuals. Numerous research
      projects have attempted to measure the impact of mental illness and related
      disorders on the ill individual, yet have traditionally neglected estimating
      potential costs accruing to family members of the ill. AIMS OF THE STUDY:
      Previous research estimating the impact of illness on the time allocation
      decisions of family caregivers has been limited in scope. I obtain estimates of
      the impact of mental illness on the probability of labor force participation and
      hours of work of all family members. The general analysis used in this study will
      pave the way for more accurate assessments of the costs of all types of illness
      and the estimates obtained will provide policy makers with a much more complete
      picture of the costs of mental illness. METHODS: The main empirical work in this
      study includes a probit estimation of labor force participation and a tobit
      regression of hours worked (including sample selection correction). The data
      sample, taken from the 1987 National Medical Expenditure Survey, is also
      partitioned by gender to clarify effects of family illness on labor supply for
      both females and males. RESULTS: Adult males are found to increase their
      probability of labor force participation in the presence of mental illness in the
      family (all else equal) when the mental illness is accompanied by a chronic
      physical illness. However, females are surprisingly found to have no significant
      impact on their probability of being a member of the labor market when a family
      member is afflicted with mental illness. On the other hand, hours of work are
      significantly reduced for both females and males when the mentally ill family
      member is afflicted with additional illnesses (physical and/or mental).
      DISCUSSION: Previous studies have traditionally not considered the effects of
      family illness on males because females are typically found to be the primary
      caregiver when a family member falls ill. The findings in this study indicate
      that men suffer reductions in their hours of work in an equivalent magnitude to
      females. Thus, males should not be ignored when estimating the opportunity costs
      of illness in families. IMPLICATIONS FOR HEALTH POLICIES: Current federal and
      state policies provide for some of the medical costs and replace some of the lost
      income of ill individuals, but generally do not support family members who are
      negatively affected by illness. This research provides evidence supporting the
      arguments of advocates for policy to ameliorate the financial burden borne by
      family members of the ill. IMPLICATIONS FOR FUTURE RESEARCH: The estimates
      obtained in this study show that women and men both need to be studied when
      determining the effects of family illness on labor supply, and should be studied
      separately to obtain clear results. Also, future research should include
      examining particular mental illnesses to see whether there is a higher cost of
      one over the other (e.g., schizophrenia versus major depression), as this may
      provide valuable information to policy makers. In addition, comparison of the
      costs of psychological disorders to chronic physical illnesses (such as cancer
      and heart disease) should be undertaken.

PMID- 11967431
TI  - Editorial.

PMID- 11967432
TI  - Depression: cost-of-illness studies in the international literature, a review.
AB  - BACKGROUND: Depression is one of the most ancient and common diseases of the
      human race and its burden on society is really impressive. This stems both from
      the epidemiological spread (lifetime prevalence rate, up to 30 years of age, was
      estimated as greater than 14.4% by Angst et al.) and from the economic burden on
      healthcare systems and society, but also as it pertains to patient well-being.
      AIMS OF THE STUDY: The scope of this review was to examine studies published in
      the international literature to describe and compare the social costs of
      depression in various countries. METHODS: A bibliographic search was performed on
      international medical literature databases (Medline, Embase), where all studies
      published after 1970 were selected. Studies were carefully evaluated and only
      those that provided cost data were included in the comparative analysis; this
      latter phase was conducted using a newly developed evaluation chart. RESULTS: 10
      abstracts were firstly selected; 46 of them underwent a subsequent full paper
      reading, thus providing seven papers, which were the subject of the in-depth
      comparative analysis: three studies investigated the cost of depression in the
      USA, three studies in the UK and one study was related to Italy. All the studies
      examined highlight the relevant economic burden of depression; in 1990, including
      both direct and indirect costs, it accounted for US$ 43.7 billion in the US (US$
      65 billion, at 1998 prices) according to Greenberg and colleagues, whilst direct
      costs accounted for L417 million in the UK (or US$ 962.5 million, at 1998
      prices), according to Kind and Sorensen. Within direct costs, the major cost
      driver was indeed hospitalization, which represented something in between 43 and
      75% of the average per patient cost; conversely, drug cost accounted for only 2%
      to 11% in five out of seven studies. DISCUSSION: Indeed, our review suggests that
      at the direct cost level, in both the United States and the United Kingdom, the
      burden of depression is remarkable, and this is confirmed by a recent report
      issued by the Pharmaceutical Research and Manufacturers Association (PhRMA) where
      prevalence and cost of disease were compared for several major chronic diseases,
      including Alzheimer, asthma, cancer, depression, osteoporosis, hypertension,
      schizophrenia and others: in this comparison, depression is one of the most
      significant diseases, ranked third by prevalence and sixth in terms of economic
      burden. Moreover, in terms of the average cost per patient, depression imposes a
      societal burden that is larger than other chronic conditions such as
      hypertension, rheumatoid arthritis, asthma and osteoporosis. The application of
      economic methods to the epidemiological and clinical field is a relatively recent
      development, as evidenced by the finding that, out of the seven studies examined,
      three refer to the US environment, three to the UK and one to Italy, while
      nothing was available about the cost of depression for large countries such as
      France, Germany, Spain, Japan and others. IMPLICATION FOR HEALTH CARE PROVISION
      AND USE: The high incidence of hospitalization, and the finding that drug cost
      represents only a minor component of the total direct cost of the disease,
      suggests that room is still available for disease management strategies that,
      while effectively managing the patient's clinical profile, could also improve
      health economic efficiency. IMPLICATION FOR HEALTH POLICIES: Disease management
      strategies, with particular emphasis on education, should be targeted not only at
      patients and medical professionals but also at health decision makers in order
      "to encourage effective prevention and treatment of depressive illness".
      IMPLICATIONS FOR FURTHER RESEARCH: Cost of illness studies are a very useful tool
      allowing cost data comparisons across countries and diseases: for this reason, we
      suggest that further research is needed especially in some western European
      countries to assess the true economic burden of depression on societies.

PMID- 11967433
TI  - Cost-benefit analysis of drug treatment services: review of the literature*
AB  - BACKGROUND: How valuable is public investment in treatment for drug abuse and
      dependency in the real world of everyday practice? Does drug abuse treatment
      provide benefits and how are they valued? What are the costs of obtaining
      outcomes and benefits? Cost-benefit analysis attempts to answer these questions
      in a standard analytic framework. AIMS: This paper reviews cost-benefit analyses
      with scientific merit so that analysts will have a current picture of the state
      of the research. It will also give public decision-makers information with
      regards to the available evidence for policy purposes. METHOD: Bibliographic
      searches were performed. Studies were obtained through the assistance of the
      Parklawn Health Library system, a component of the US Public Health Service.
      Selected studies were from the scientific literature with the exception of eight
      studies published as governmental reports. RESULTS: Cost-benefit studies have
      fallen into the following categories: (i) planning models for delivery systems in
      states and cities; (ii) short-term follow-up studies of individuals, (iii) single
      individual programs and (iv) state system's monitoring of outcomes. In 18 cost
      benefit studies, a persistent finding is that benefits exceed costs, even when
      not all benefits are accounted for in the analysis. Much variation is found in
      the implementation of cost-benefit methods, and this is detailed across
      discussions of effectiveness, benefits and costs. Studies have emphasized the
      cost savings to society from the reduction in external costs created by the
      behavioral consequences of addiction and drug use. DISCUSSION: Economic analysis
      of drug treatment requires sophisticated conceptualization and measurement. Cost
      benefit analysis of drug treatment has been a significant analytical exercise
      since the early 1970s when the public drug treatment system was founded in the
      United States. CONCLUSION: Drug abuse treatment services may be considered as
      contributing positive economic returns to society. However, considerable work
      needs to be done to standardize methods used in the studies. A striking area of
      omission is the absence of studies for adolescents and only one for women in
      treatment. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Finding a positive net
      social benefit should assist policy-makers with decisions related to drug abuse
      treatment expenditures. Additional work on allocation of budget dollars across
      various drug treatment services will be needed. IMPLICATIONS FOR HEALTH POLICY
      FORMULATION: Government agencies and other stakeholders in national health care
      systems must realize that cost-benefit studies are an important tool for decision
      making. Rational strategies can only be addressed by examining alternatives for
      the efficient allocation and equitable distribution of scarce resources.
      IMPLICATIONS FOR FURTHER RESEARCH: Future research should focus on standardizing
      the methods used in the cost-benefit analysis. Extensions should examine methods
      related to the willingness-to-pay approach. Studies are needed for drug abuse
      treatment targeted to adolescents and women. More studies should be published in
      the scientific literature.

PMID- 11967434
TI  - Schizophrenia, substance use disorders and medical co-morbidity.
AB  - OBJECTIVES: This study compared medical treatment costs of adults with
      schizophrenia to adults with both substance use disorders and schizophrenia.
      METHODS: This cross-sectional observational study used a paid claims data base to
      identify 6884 adults treated for schizophrenia. Twenty percent of these also had
      substance use disorder. We report the costs and likelihood of hospitalization for
      eight common medical diseases, and the categories of injuries and poisoning, and
      ill defined conditions. Multivariate analyses were used to adjust rates of
      treatment for age and sex differences in the comparison groups. RESULTS: There
      were higher rates of treatment for five of the eight medical disorders, higher
      treatment costs for two of the medical disorders and much higher costs for
      psychiatric treatment among those with comorbid substance use disorders. Both
      groups had high rates of treatment in the categories of injury and poisoning and
      ill defined conditions. CONCLUSIONS: Closer working relationships among mental
      health and medical professionals are needed to care for those with schizophrenia
      and substance use disorders: first, greater attention to the treatment of
      substance use disorders may improve the health status of those with
      schizophrenia, reduce their costly medical and psychiatric care and stabilize
      their psychiatric condition, and second, continuity of care among professionals
      may promote willingness to seek medical attention or alleviate misunderstandings
      when adults with schizophrenia present with medical problems.

PMID- 11967435
TI  - Capitated payments for mental health patients: a comparison of potential
      approaches in a public sector population.
AB  - BACKGROUND: Both private and public health care systems have embraced capitated
      reimbursement as a method of controlling costs. AIMS OF THE STUDY: This study
      explores the financial implications of using reimbursement models based on
      clinically based patient classification schemes to distribute funds for the
      treatment of mental health patients in the Department of Veterans Affairs (VA).
      METHODS: We identified 53700 veterans treated in VA specialty mental health
      outpatient clinics during the first 2 weeks of fiscal year (FY) 1991 for whom
      relevant clinical data were available. We calculated total utilization and costs
      for this sample during the remainder of FY 1991 using VA administrative databases
      and simulated hypothetical distributions of funds based on seven alternative
      capitation models. The resulting distributions of funds across service networks
      and facility types were compared to actual expenditures. RESULTS: Approximately
      8% of overall VA budget was redistributed under a simple capitated scheme, and
      some individual networks and facility types experienced changes in funding of
      over 30%. Models based on clinical data resulted in only minor differences from
      average-cost reimbursement. Substantial variation in practice style was observed
      across Veterans Integrated Service Networks (VISNs), which was significantly
      associated with funding shifts under capitation. DISCUSSION: A simple capitated
      payment scheme would result in large changes in funding for some VISNs.
      Adjustments for case mix did not substantially affect patterns of redistribution.
      Patterns of redistribution appear to reflect large differences in practice style
      across VISNs. Although a capitated system will create incentives to reduce such
      variation, the effect of such shifts on patient well-being is unknown.
      IMPLICATIONS FOR HEALTH POLICIES: Any capitated system will create incentives to
      provide a uniform standard of care. In our analyses, the capitation rate was
      based on the average cost per treated patient in each category; however rates
      could be set higher or lower as policy makers deem necessary. The standard of
      care associated with the average cost is not necessarily the "correct" level of
      care. IMPLICATIONS FOR FURTHER RESEARCH: Our analyses explore the implications of
      capitated systems for mental health patients in the absence of behavioral change.
      Further research is needed to determine how providers actually respond to the
      different incentives created by capitation and what impact these changes have on
      patient well-being. lems.

PMID- 11967436
TI  - Resource distribution in mental health services: changes in geographic location
      and use of personnel in Norwegian mental health services 1979-1994.
AB  - BACKGROUND: During the last decades, a central aim of Norwegian health policy has
      been to achieve a more equal geographical distribution of services. Of special
      interest is the 1980 financial reform. Central government reimbursements for the
      treatment of in-patients were replaced by a block grant to each county, based on
      indicators of relative "need". AIMS OF THE STUDY: The aim of this paper is to
      assess whether the distribution of specialized mental health services did take
      the course suggested by the proponents of the reform (i.e. a more equal
      distribution), or the opposite (i.e. a more unequal distribution) as claimed by
      the opponents. METHODS: Man year per capita ratios were used as indicators for
      the distribution of mental health services by county. Ratios were estimated for
      "all personnel", and for MDs and psychologists separately. Man years were
      assigned to counties by location of services (i.e. in which county the services
      were produced), and by residence of users (i.e. in which county the services were
      consumed). Indicators of geographic variation were estimated using the standard
      deviation (STD) as a measure of absolute variation, and the coefficient of
      variation (CV) and the Gini index as indicators of relative variation. Indicators
      were estimated for 1979, 1984, 1989 and 1994, based on data for all specialized
      adult mental health services in the country. Changes in distributions over the
      period were tested, using Levene's test of homogeneity. RESULTS: Relative
      variations in the distribution of personnel by location of services were
      substantially reduced over the period, the CV being reduced by more than 50% for
      all groups. Variations in the personnel ratios by residence of users were smaller
      at the start of the period, and the reductions were also smaller. Still, relative
      variations were reduced by 20-35, 40 and 60% approximately for "all personnel",
      MDs and psychologists respectively. In spite of a major increase in the supply of
      MDs and psychologists, absolute variations in the personnel ratios were in all
      cases either reduced, or fairly stable. These results give little support to the
      views expressed by the opponents of the 1980 reform, although the main result
      seems to have been relocations in the production of services, more than re
      distributions in the consumption of services. DISCUSSION: These results can be
      seen as a result of three aspects of the reform: 1 Distributing government grants
      to counties in their capacity as users of services rather than producers of
      services. This shift has primarily facilitated relocations in the production of
      services. 2 Relocation of services was also expected to produce a more equal
      distribution in the use of services, since reduced distances would increase
      accessibility. This, however, was counteracted by increased county control with
      use of services in other counties. 3 Distribution of grants based on "needs"
      rather than services produced was expected to produce a more equal distribution
      in the use of services. This effect seems to have been less than expected,
      probably because counties with high reimbursements under the old system also
      provided services to people from other counties. Other policy reforms have,
      however, contributed to the results. These reforms include increased supply of
      personnel, de-institutionalization of services, regionalization/sectorization of
      services, and the establishment of smaller psychiatric units in general
      hospitals. POLICY IMPLICATIONS: In recent years the 1980 reform has been under
      attack; partly due to alleged inequalities created by the system. As a result of
      the critique, government reimbursements for in-patient treatment have been
      reintroduced for general hospital services. In mental health services, more
      resources are distributed to specific projects. According to this study, this
      shift in policy is based on faulty premises and might lead to greater
      inequalities in the future.

PMID- 11967437
TI  - How can policy makers use available evidence on the cost benefits of drug
      treatement?
AB  - All the studies on the cost benefits of drug treatment reviewed by Cartwright in
      this issue suggest benefits outweigh costs by some margin. What lessons does this
      review of mainly American data have for European policy makers? Drug treatments
      are associated with a wide range of consequences outside the health sector and
      there are considerable differences in treatment regimes across countries. This
      could well influence results. There are also considerable differences in
      methodologies used across available studies and many lack strong study designs.
      An interesting feature is the lack of valuation of individual drug users
      benefits, does this imply that policy makers in the US do not care about drug
      misusers. Would the situation be the same in Europe or other parts of the world?
      There is a lot of research to be done and perhaps specific guidelines are
      required to ensure economic evaluations in this area can be used to guide policy
      decisions with more confidence.

PMID- 11967438
TI  - Editorial.

PMID- 11967439
TI  - The interdependence of mental health service systems: the effects of VA mental
      health funding on veterans' use of state mental health inpatient facilities.
AB  - BACKGROUND: There are relatively few published data on how the financial
      structures of different health systems affect each other. With increasing
      financial restrictions in both public and private healthcare systems, it is
      important to understand how changes in one system (e.g. VA mental healthcare)
      affect utilization of other systems (e.g. state hospitals). AIMS OF THE STUDY:
      This study utilizes data from state hospitals in eight states to examine the
      relationship of VA per capita mental health funding and state per capita mental
      health expenditures to veterans' use of state hospitals, adjusting for other
      determinants of utilization. METHODS: This study utilized a large database that
      included records from all male inpatient admissions to state hospitals between
      1984 and 1989 in eight states (n = 152541). Funding levels for state hospitals
      and VA mental health systems were examined as alternative enabling factors for
      veterans' use of state hospital care. Logistic regression models were adjusted
      for other determinants of utilization such as socio-economic status, diagnosis,
      travel distances to VA and non-VA facilities and the proportion of veterans in
      the population. RESULTS: The single strongest predictor of whether a state
      hospital patient would be a veteran was the level of VA mental healthcare funding
      (OR = 0.81 per $10 of funding per veteran in the population, p = 0.0001), with
      higher VA funding associated with less use of state hospitals by veterans. Higher
      per capita state funding, reciprocally, increased veterans' use of state
      hospitals. We also calculated elasticities for state hospital use with respect to
      VA mental healthcare funding and with respect to state hospital per capita
      funding. A 50% increase in VA per capita mental health spending was associated
      with a 30% decrease in veterans' use of state hospitals (elasticity of -0.6).
      Conversely, a 50% increase in state hospital per capita funding was associated
      with only an 11% increase in veterans' use of state hospitals (elasticity of
      0.06). IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: These data indicate that
      per capita funding for state hospitals and VA mental health systems exerts a
      significant influence on service use, apparently mediated by the effect on supply
      of mental health services. Veterans are likely to substitute state hospital care
      for VA care when funding restrictions limit the availability of VA mental health
      services. However, due to the relative sizes of the two systems, VA funding has a
      larger effect than state hospital funding upon state hospital use by veterans.
      IMPLICATIONS FOR HEALTH POLICIES: These data indicate that changes in the
      organizational and/or financial structure of any given healthcare system have the
      potential to affect surrounding systems, possibly quite substantially. Policy
      makers should take this into account when making decisions, instead of
      approaching systems as independent, as has been traditional. IMPLICATIONS FOR
      FURTHER RESEARCH: Further research is needed in two areas. First, these results
      should be replicated in other systems of care using more recent data. Second,
      these results are difficult to generalize to individual behavior. Future research
      should examine the extent and individual determinants of cross-system use.

PMID- 11967440
TI  - Organizing mental health services: an evidence-based approach.
AB  - BACKGROUND AND AIMS: Health policy makers and program developers seek evidence
      based guidance on how to organize and finance mental health services. The Swedish
      Council on Technology Assessment in Health Care (SBU) commissioned a conceptual
      framework for thinking about health care services as a medical technology. The
      following framework was developed, citing empirical research from mental health
      services research as the case example. FRAMEWORK: Historically, mental health
      services have focused on the organization and locus of care. Health care settings
      have been conceptualized as medical technologies, treatments in themselves. For
      example, the field speaks of an era of "asylum treatment" and "community care".
      Hospitals and community mental health centers are viewed as treatments with
      indications and "dosages", such as length of stay criteria. Assessment of mental
      health services often has focused on organizations and on administrative science.
      There are two principal perspectives for assessing the contribution of the
      organization of services on health. One perspective is derived from clinical
      services research, in which the focus is on the impact of organized treatments
      (and their most common settings) on health status of individuals. The other
      perspective is based in service systems research, in which the focus is on the
      impact of organizational strategies on intermediate service patterns, such as
      continuity of care or integration, as well as health status. METHODS: Examples of
      empirical investigations from clinical services research and service systems
      research are presented to demonstrate potential sources of evidence to support
      specific decisions for organizing mental health services. RESULTS: Evidence on
      organizing mental health services may be found in both types of services
      research. In clinical services research studies, service settings are viewed as
      treatments (e.g. "partial hospitalization"), some treatments are always embedded
      in a service matrix (e.g. assertive community treatment), and, where some
      treatments are organizationally combined (e.g. "integrated treatment" for co
      occurring mental disorder and substance abuse), sometimes into a continuum of
      care. In service system research, integration of services and of the service
      system are the main focus of investigation. Studies focus on horizontal and
      vertical integration, primary care or specialty care and local mental health
      authorities - each of which may be conceptualized as a health care technology
      with a body of evidence assessing its effectiveness. IMPLICATIONS: A conceptual
      framework for assessing the organization of services as a health care technology
      focuses attention on evidence to guide program design and policy development.
      Mental health services research holds promise for such decision-making guidance.

PMID- 11967441
TI  - Organization and financing of mental health care in Poland.
AB  - ORGANIZATION OF CARE: Health care is provided to patients with mental disorders
      by the state health care facilities as well as by social help agencies. Mental
      health care services are provided mostly by mental health facilities and partly
      by primary care units. Outpatient clinics, separate for psychiatric patients and
      substance abusers, are the most numerous mental health care units, amounting to a
      total of 1120. Intermediate care facilities include 110 day hospitals, 23
      community mobile teams and ten hostels. The number of hospital beds amounts to
      31913, i.e. 8.3 beds per 10000 population. 80% of beds are located in mental
      hospitals. TRENDS OF DEVELOPMENT: The trends in mental health care development
      are outlined in the Mental Health Programme and accompanying documents accepted
      by the Minister of Health and Social Welfare. The programme defines specific
      goals to be achieved by the year 2005 in the primary, secondary and tertiary
      prevention of mental disorders. In the domain of mental health care accessibility
      the most important goals are the following: a significant reduction in the number
      of beds in large mental hospitals, a marked (nearly threefold) rise in the number
      of beds in psychiatric wards at general hospitals and a significant increase in
      the number of community-based forms of care (e.g. a fourfold rise in the number
      of day hospitals). FINANCING OF CARE: Before 1999, the health care system was
      financed from the state budget and the health care spendings were subject to a
      political auction each year. Allocation of funds among hospitals and health care
      centres was based on the total previous year budgetary spendings of particular
      facilities and did not take into account a detailed cost analysis. Such a
      financing approach, although giving a feeling of a relative financial safety, did
      not encourage health care facilities to introduce an organizational flexibility
      and to expand the scope of their services. In psychiatry, it manifested itself in
      a very slow development of some community psychiatry forms (mostly day hospitals,
      mobile community teams and hostels). The Health Care Institutions Act has created
      a legal framework for the financial management of health care units in their new,
      independent form. Conditions for health care financing through regional sickness
      funds were thus created. The financing is currently based on contracts made by
      sickness funds with health care facilities for specific health services. Both the
      quantity and price of services should be mutually negotiated. Some simplified
      measures of services offered were used during the first insurance financing year.
      In mental hospitals and day hospitals it was a person-day; in out-patient care it
      was a visit. Both cost indicators were aggregated, including all the components
      present so far in the functioning a given unit.

PMID- 11967442
TI  - Empirical evidence on the demand for carve-outs in employment group mental health
      coverage.
AB  - BACKGROUND AND AIMS OF THE STUDY: The use of specialized behavioral health
      companies to manage mental/health benefits has become widespread in recent years.
      Recent studies have reported on the cost and utilization impacts of behavioral
      health carve-outs. Yet little previous research has examined the factors which
      lead employer-based health plans to adopt a carve-out strategy for mental health
      benefits. The examination of these factors is the main focus of our study. Our
      empirical analysis is also intended to explore several hypotheses (moral hazard,
      adverse selection, economies of scale and alternate utilization management
      strategies) that have recently been advanced to explain the popularity of carve
      outs. METHODS: The data for this study are from a survey of employers who have
      long-term disability contracts with one large insurer. The analysis uses data
      from 248 employers who offer mental health benefits combined with local market
      information (e.g. health care price proxies, state tax rates etc), state
      regulations (mental health and substance abuse mandate and parity laws) and
      employee characteristics. Two different measures of carve-out use were used as
      dependent variables in the analysis: (1) the fraction of health plans offered by
      the employer that contained carve-out provisions and (2) a dichotomous indicator
      for those employers who included a carve-out arrangement in all the health plans
      they offered. RESULTS: Our results tended to support the general cost-control
      hypothesis that factors associated with higher use and/or costs of mental health
      services increase the demand for carve-outs. Our results gave less consistent
      support to the argument that carve-outs are demanded to control adverse
      selection, though only a few variables provided a direct test of this hypothesis.
      The role of economies of scale (i.e., group size) and the effectiveness of
      alternative strategies for managing moral hazard costs (i.e., HMOs) were
      confirmed by our results. DISCUSSION: We considered a number of different
      hypotheses concerning employers' demands for mental health carve-outs and found
      varying degrees of support for these hypotheses in our data. Our results tended
      to support the general cost-control hypothesis that factors associated with
      higher use and/or costs of mental health services increase the demand for carve
      outs. LIMITATIONS: Our database includes a small number of relatively large
      employers and is not representative of employers nationally. Our selection
      criteria, concerning size and the requirement that some employees are covered by
      LTD insurance, probably resulted in a study sample that offers richer benefits
      than do employers nationally. Our employers also report a higher percentage of
      salaried employees relative to the national data. Another deficiency in the
      current study is the lack of detailed information on the socio-demographic and
      behavioral characteristics of covered employees. Finally, the cross-sectional
      nature of our analysis raises concerns about susceptibility of our findings to
      omitted variables bias. IMPLICATIONS FOR FURTHER RESEARCH: Research with more
      information on covered employee characteristics will allow for a stronger test of
      the general hypothesis that factors associated with a higher demand for services
      are also associated with a higher demand for carve-outs. Also, future analyses
      that capture the experience of states that have recently passed mandate and
      parity laws, and that use pooled data to control for omitted variables bias, will
      provide more definitive evidence on the relationship between these laws and carve
      out demand.

PMID- 11967443
TI  - Using randomized controlled trials to evaluate socially complex services:
      problems, challenges and recommendations.
AB  - BACKGROUND: Following the lead of evidence-based medicine, practice based on
      effectiveness research has become the new gold standard of contemporary public
      policy. Studies of this sort are increasingly demanded to evaluate services
      provided by mental health, social services and criminal justice systems. AIMS:
      The paper questions whether the simple randomized controlled trial (RCT) paradigm
      as applied in clinical trials can be used "off the rack" to evaluate socially
      complex service (SCS) interventions. These are services that are characterized by
      complex, diverse and non-standardized staffing arrangements; ambiguous protocols;
      hard-to-define study samples and unevenly motivated subjects and dependence on
      broader social environments. The difficulty of ensuring precise protocols,
      equivalent groups (tied to a meaningful target population) and neutral and
      equivalent trial environments under real world conditions are explored, as are
      the implications of not achieving standardization and equivalence. METHODS:
      Limitations of effectiveness research as a research tool and information source
      are examined by comparing the assumptions underpinning the simple RCT to the
      characteristics of SCS interventions, as illustrated by programs targeted to
      mentally disordered offenders in Britain. RESULTS: SCSs violate the assumptions
      underpinning the simple RCT model in ways that draw into sharp question the
      validity, reliability and generalizability of inferences of SCS trials.
      DISCUSSION: The RCT is not a panacea. Effectiveness research of SCS interventions
      that is based on the RCT model is unlikely to yield valid, reliable and
      generalizable inferences without becoming more complex in design and more
      sensitive to issues of selection bias, unmeasured variables and endogeneity. Ten
      recommendations are offered for stylizing the RCT design to the characteristics
      of socially complex services. IMPLICATIONS: It remains an empirical issue whether
      RCT-based services effectiveness research can inform mental health policy.
      Without major design innovations, it is more likely that the information
      generated by this research will have limited practical use, especially if the RCT
      model is unable to control for the effect of social complexity and the
      interaction between social complexity and dynamic systemic change. Scientific
      evaluations of services make clinical and economic sense so long as they are
      designed to meet the challenges of the services of which they promise greater
      knowledge.

PMID- 11967444
TI  - Big studies, simple lessons.
AB  - Goldman describes how service systems research examines the impact of economic
      and organizational strategies designed to promote particular service combinations
      (such as continuity of care) and inhibit others (such as preferentially serving
      only those individuals who are the easiest to treat). The recurring theme from
      the large services research initiatives is that the content of care, as well as
      the organization and financing of care, matters. This theme is distinct from what
      these large services research projects were designed to assess, which speaks both
      to the unexpected benefits from these massive studies and the need for more
      efficient tools to examine the interrelationships among the organization,
      financing and content of care.

PMID- 11967445
TI  - A programmatic approach to socially complex intervention development.
AB  - First used in psychiatry to study pharmacological treatments, the randomized
      controlled trial provides the most powerful test of the relative effectiveness of
      two or more interventions. Applying RCT methodology to socially complex service
      interventions, however, presents unique challenges that derive from difficulties
      in treatment standardization, attaining study sample equivalence and controlling
      for environmental variations. These challenges can be managed when intervention
      development proceeds along a programmatic trajectory that spans discovery,
      development, efficacy, effectiveness and practice research.

PMID- 11967446
TI  - Editorial.

PMID- 11967447
TI  - Service inputs and costs of care related to outcomes among cognitively impaired
      nursing home residents.
AB  - BACKGROUND: There are over 17 000 nursing homes in the United States. Within
      these, special care units (SCUs) provide a separate residential and/or activity
      locus for residents, and are expected to provide more staff time and more
      specialized staff assignments. This paper addresses a fundamental issue relating
      to the nature, quality and quantity of resident care inputs: what impacts of SCUs
      are associated with added service inputs, and thus with personnel costs,
      recognizing that personnel account for the majority of costs associated with
      nursing home care? AIMS OF THE STUDY: The aim of this aspect of the study was to
      determine the extent to which additions of staff would result in a diminution of
      deviant behaviors among residents of special care and of traditional care units.
      METHOD: The data were collected from a random sample of ten downstate nursing
      homes located in New York State. Using rigorous sampling procedures, random
      samples of 40 residents were drawn from each of the facilities, equally divided
      between special care unit and traditional care unit residents. Thus, the sampling
      design involved two levels of clustering: subjects were clustered within units
      and units were clustered within facilities. The observational behaviour measure
      was taken from the INCARE (institutional version of the Comprehensive Assessment
      and Referral Evaluation). The behavioral observation measure contains 23 items
      such as "disruptive of others", "picks/pulls clothing", "repetitive movements",
      "repetitive questioning"and "wandering". Each item is rated as to frequency of
      occurrence; ratings are collected on three occasions, and averaged. Outcome and
      covariate data (e.g., behavior and cognition) were collected by trained research
      staff who visited each site for three to four weeks of intensive data collection,
      accomplished through direct resident interviews, staff interviews and
      questionnaires and chart data abstraction. The clinical staff time data were
      collected using the InfoAide system, whereby each care provider used a portable
      barcode scanner to record the type of care given, the recipient and the duration
      of care. A random effects model using the SAS mixed procedure was applied to the
      data; adhering to this model, some effects were fixed and some random. The random
      effects were comprised of the subject (intercept or subject starting point at
      baseline) and the unit; used here was restricted maximum likelihood (REML) with
      the EM algorithm. RESULTS: There was a significant reduction of behavior disorder
      associated with more provision of aide time in SCUs as contrasted with non-SCUs.
      The greater the service provided, the greater the slope, i.e., the greater the
      reduction. That is, while SCU residents showed improvements in behavior
      accompanying increases in aide time, no such change was observed among non-SCU
      residents. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The significant effect
      of SCU + time + aide-minutes indicates that more aide time on SCUs was associated
      with improvement in behavior. It appears that the important ingredient in
      relation to the reduction of behavior disorder is not membership in an SCU per
      se, but the provision of more aide time within SCUs. Those SCUs that provide more
      aide time have a better behavior outcome. Thus, these findings point to
      additional paths for exploration, i.e., future research needs to focus on
      elements of SCUs such as the available amounts of program and staff resources
      rather than on SCU status alone.

PMID- 11967448
TI  - Risk adjustment for high utilizers of public mental health care.
AB  - BACKGROUND: Publicly funded mental health systems are increasingly implementing
      managed care systems, such as capitation, to control costs. Capitated contracts
      may increase the risk for disenrollment or adverse outcomes among high cost
      clients with severe mental illness. Risk-adjusted payments to providers are
      likely to reduce providers' incentives to avoid or under-treat these people.
      However, most research has focused on Medicare and private populations, and risk
      adjustment for individuals who are publicly funded and severely mentally ill has
      received far less attention. AIMS OF THE STUDY: Risk adjustment models for this
      population can be used to improve contracting for mental health care. Our
      objective is to develop risk adjustment models for individuals with severe mental
      illness and assess their performance in predicting future costs. We apply the
      risk adjustment model to predict costs for the first year of a pilot capitation
      program for the severely mentally ill that was not risk adjusted. We assess
      whether risk adjustment could have reduced disenrollment from this program.
      METHODS: This analysis uses longitudinal administrative data from the County of
      Los Angeles Department of Mental Health for the fiscal years 1991 to 1994. The
      sample consists of 1956 clients who have high costs and are severely mentally
      ill. We estimate several modified two part models of 1993 cost that use 1992
      client-based variables such as demographics, living conditions, diagnoses and
      mental health costs (for 1992 and 1991) to explain the variation in mental health
      and substance abuse costs. RESULTS: We find that the model that incorporates
      demographic characteristics, diagnostic information and cost data from two
      previous years explains about 16 percent of the in-sample variation and 10
      percent of the out-of-sample variation in costs. A model that excludes prior cost
      covariates explains only 5 percent of the variation in costs. Despite the
      relatively low predictive power, we find some evidence that the disenrollment
      from the pilot capitation initiative input have been reduced if risk adjustment
      had been used to set capitation rates. DISCUSSION: The evidence suggests that
      even though risk adjustment techniques have room to improve, they are still
      likely to be useful for reducing risk selection in capitation programs. Blended
      payment schemes that combine risk adjustment with risk corridors or partial fee
      for-service payments should be explored. IMPLICATIONS FOR HEALTH CARE PROVISION,
      USE, AND POLICY: Our results suggest that risk adjustment methods, as developed
      to data, do not have the requisite predictive power to be used as the sole
      approach to adjusting capitation rates. Risk adjustment is informative and
      useful; however, payments to providers should not be fully capitated, and may
      need to involve some degree of risk sharing between providers and public mental
      health agencies. A blended contract design may further reduce incentives for risk
      selection by incorporating a partly risk-adjusted capitation payment, without
      relying completely on the accuracy of risk adjustment models. IMPLICATIONS FOR
      FURTHER RESEARCH: Risk adjustment models estimated using data sets containing
      better predictors of rehospitalization and more precise clinical information are
      likely to have higher predictive power. Further research should also focus on the
      effect of combination contract designs.

PMID- 11967449
TI  - Lost productivity among full-time workers with mental disorders.
AB  - BACKGROUND: Few studies have systematically compared the relationship between
      lost work productivity (work impairment) and mental disorders using population
      surveys. AIMS: (1) To identify the importance of individual mental disorders and
      disorder co-occurrences (comorbidity) as predictors of two measures of work
      impairment over the past month - work loss (number of days unable to perform
      usual activities) and work cutback (number of days where usual activities were
      restricted); (2) to examine whether different types of disorder have a greater
      impact on work impairment in some occupations than others; (3) to determine
      whether work impairment in those with a disorder is related to treatment seeking.
      METHOD: Data were based on full-time workers identified by the Australian
      National Survey of Mental Health and Well-Being, a household survey of mental
      disorders modeled on the US National Comorbidity Survey. Diagnoses were of one
      month DSM-IV affective, anxiety and substance-related disorders. Screening
      instruments generated likely cases of ICD-10 personality disorders. The
      association of disorder types and their co-occurrences with work impairment was
      examined using multivariate linear regression. Odds ratios determined the
      significance of mental disorder prevalence across occupations, and planned
      contrasts were used to test for differences in work impairment across occupations
      within disorder types. The relationship between work impairment and treatment
      seeking was determined for each broad diagnostic group with t-tests. RESULTS:
      Depression, generalized anxiety disorder and personality disorders were
      predictive of work impairment after controlling for impairment due to physical
      disorders. Among pure and comorbid disorders, affective and comorbid anxiety
      affective disorders respectively were associated with the greatest amount of work
      impairment. For all disorders, stronger associations were obtained for work
      cutback than for work loss. No relationship was found between type of occupation
      and the impact of different types of disorder on work impairment. Only 15% of
      people with any mental disorder had sought help in the past month. For any mental
      disorder, significantly greater work loss and work cutback was associated with
      treatment seeking, but comparisons within specific disorder types were not
      significant. DISCUSSION: A substantial amount of lost productivity due to mental
      disorders comes from within the full-time working population. The greater impact
      of mental disorders on work cutback compared to work loss suggests that work
      cutback provides a more sensitive measure of work impairment in those with mental
      disorders. Work impairment was based on self-report only. While there is evidence
      for the reliability of self-assessed work loss days, no reliability or validity
      studies have been conducted for work cutback days. The low rates of treatment
      seeking are a major health issue for the workforce, particularly for affective
      and anxiety disorders, which are important predictors of lost productivity.
      IMPLICATIONS FOR HEALTH POLICIES AND FURTHER RESEARCH: Future research should
      investigate the validity of work cutback, given its importance as a measure of
      lost productivity in people with mental disorders. Employers need to be aware of
      the extent to which mental disorders affect their employees so that effective
      work place interventions can take place. Treatment should be targeted at people
      with affective and anxiety disorders, particularly where they co-occur.

PMID- 11967451
TI  - Income and employment among homeless people: the role of mental health, health
      and substance abuse.
AB  - BACKGROUND: The homeless population is among the poorest of the poor in the
      United States. Employment and government programs are potential sources of
      income, but many homeless people face potential barriers to work: many have
      serious mental and physical disabilities, and many more have alcohol and drug
      disorders. As a result, most homeless who work do so either for a few hours per
      day or only some days, which provides little income. General Assistance, a public
      program of last resort, also provides a low level of income support. More income
      might be gained through higher levels of work or participation in income support
      programs for people with disabilities. AIMS OF THE STUDY: To investigate the
      characteristics of homeless people that impede them in the labor market and in
      government program participation, paying particular attention to their mental and
      physical health, as well as their alcohol and drug problems. DATA: Data are from
      a survey of the homeless population in Alameda County, California, conducted from
      1991 to 1993. Our sample is 471 homeless adults randomly selected from area
      shelters and meal providers, who were reinterviewed approximately 6 months later,
      regardless of domiciliary status. Mental health and substance use problems were
      assessed using the Diagnostic Interview Schedule, a structured, psychiatric
      interview that uses criteria based on the American Psychiatric Association's
      Diagnostic and Statistical Manual of Mental Disorders 3rd edn (revised).
      Employment between the first and second interview is categorized as none, low
      level (less than 6 hours a day or fewer than half the days between interviews) or
      higher level (at least 6 hours a day for at least half the days). ANALYTICAL
      PROCEDURES: The models of employment status and program participation are
      recursive in that homelessness at the first wave of the survey is treated as
      given. Thus we explore whether, given their initial homelessness, persons can
      gain or maintain access to income between the two interviews, conditional on the
      sample member's homelessness, health and disability at the first interview. Using
      maximum-likelihood methods, we estimate a generalized ordered logit model of
      whether the person works not at all, at a low level or at a higher level.
      Participation in disability programs and GA are estimated as probit models over
      the subsamples of potentially eligible participants. RESULTS: While a
      surprisingly large number of homeless people work, few homeless persons are able
      to generate significant earnings from employment alone. Physical health problems
      that limit work or daily activities, in particular, are barriers to employment.
      Drug and alcohol abuse and dependence are positively associated with lower work
      level but are negatively related to higher work level. Program participation is
      quite low relative to eligibility. Those with physical health problems are
      substantially more likely than those with mental health problems to be in the
      more generous disability programs. Substance use disorders are also a barrier to
      participation in disability programs. DISCUSSION: Mental health, health and
      disability play a large role in the employment and program participation of the
      homeless and persons at risk for homelessness. Physical disabilities are a
      barrier to employment, and those with substance use disorders are most likely to
      work at lower levels that provide less income. Rates of participation in
      government programs are low, and people with major mental disorders have
      especially low participation rate in disability programs. The low rates of
      participation, particularly in the disability programs, suggest the need for
      continued research in improving access to income support programs among eligible
      homeless populations.

PMID- 11967450
TI  - Economic impact of a specialist outreach team in residential and nursing home
      settings.
AB  - BACKGROUND: The results of a randomized controlled trial have indicated that a
      training and educational programme for staff in nursing or residential homes may
      result in reductions in levels of depression and levels of cognitive impairment
      for residents presenting with an active management problem. The training and
      educational intervention consisted of members of a hospital outreach team who
      presented a series of 1 hour seminars on topics which staff had indicated would
      improve their knowledge and skills. AIMS OF THE STUDY: The aim of this study was
      to present an exploratory analysis of the impact on costs associated with
      providing an old age psychiatry outreach team giving training and education for
      staff in nursing and residential homes. METHOD: For the economic study, a
      societal perspective was employed. Measures of resource use and costs to the
      health service, social and community services and the nursing and residential
      homes were analysed for 120 residents from 12 nursing or residential homes, as
      part of a randomized controlled trial to assess a training package provided in
      residential and nursing homes. Cost estimates were based on estimates from
      generalized estimated equations. To allow for clustering effects within homes,
      the unit of randomization was the home as opposed to the individual. To ensure
      models were correctly specified, several tests including the Ramsey RESET test
      were employed. RESULTS: There were no significant differences in the total cost
      per person in the homes that received the intervention and the control homes.
      This study has shown that the additional cost of providing the specialist
      outreach team was likely to be covered by reductions in the use of other
      resources such as GP visits to nursing and residential homes. Therefore, though
      the study had limitations, it appeared that improved care could be provided at
      little or no extra cost. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The
      evidence presented suggests that the specialist outreach team was unlikely to add
      to the total cost of caring for residents in nursing and residential homes. This
      finding combined with the benefits in terms of lower levels of depression and
      cognitive impairment suggested that the intervention was good value for money.
      The intervention should be considered for use in other nursing and residential
      homes.

PMID- 11967452
TI  - Addiction:entries and exits. Edited by Jon Elster. New York: Sage, 1999.

PMID- 11967453
TI  - Editorial.

PMID- 11967454
TI  - Using epidemiological data to model efficiency in reducing the burden of
      depression*
AB  - BACKGROUND: The Global Burden of Disease study has suggested that mental
      disorders are the leading cause of disability burden in the world. This study
      takes the leading cause of mental disorder burden, depression, and trials an
      approach for defining the present and optimal efficiency of treatment in an
      Australian setting. AIMS OF THE STUDY: To examine epidemiological and service use
      data for depression to trial an approach for modelling (i) the burden that is
      currently averted from current care, (ii) the burden that is potentially
      avertable from a hypothetical regime of optimal care, (iii) the efficiency or
      cost-effectiveness of both current and optimal services for depression and (iv)
      the potential of current knowledge for reducing burden due to depression, by
      applying the WHO five-step method for priorities for investment in health
      research and development. METHODS: Effectiveness and efficiency were calculated
      in disability adjusted life years (DALYs) averted by adjusting the disability
      weight for people who received efficacious treatment. Data on service use and
      treatment outcome were obtained from a variety of secondary sources, including
      the Australian National Survey of Mental Health and Wellbeing, and efficacy of
      individual treatments from published meta-analyses expressed in effect sizes.
      Direct costs were estimated from published sources. RESULTS: Fifty-five percent
      of people with depression had had some contact with either primary care or
      specialist services. Effective coverage of depression was low, with only 32% of
      cases receiving efficacious treatment that could have lessened their severity
      (averted disability). In contrast, a proposed model of optimal care for the
      population management of depression provided increased treatment contacts and a
      better outcome. In terms of efficiency, optimal care dominated current care, with
      more health gain for less expenditure (28 632 DALYs were averted at a cost of
      AUD295 million with optimal care, versus 19 297 DALYs averted at a cost of AUD720
      million with current care). However, despite the existence of efficacious
      technologies for treating depression, only 13% of the burden was averted from
      present active treatment, primarily because of the low effective coverage.
      Potentially avertable burden is nearly three times this, if effective treatments
      can be delivered in appropriate amounts to all those who need it. DISCUSSION:
      This paper reports a method to calculate the burden currently averted from cross
      sectional survey data, and to calculate the burden likely to be averted from an
      optimal programme estimated from randomized controlled trial data. The approach
      taken here makes a number of assumptions: that people are accurate in reporting
      their service use, that effect sizes are a suitable basis for modelling
      improvements in disability and that the method used to translate effect sizes to
      disability weight change is valid. The robustness of these assumptions is
      discussed. Nonetheless it would appear that while optimal care could do more than
      present services to reduce the burden of depression, current technologies for
      treating depression are insufficient. IMPLICATIONS FOR HEALTH CARE PROVISION AND
      USE: There is an urgent need to educate both clinicians (primary and specialist)
      and the general public in the effective treatments that are available for
      depression. IMPLICATIONS FOR HEALTH POLICIES: Over and above implementing
      treatments of known efficacy, more powerful technologies are needed for the
      prevention and treatment of depression. IMPLICATIONS FOR FURTHER RESEARCH:
      Modelling burden averted from a variety of secondary sources can introduce bias
      at many levels. Future research should examine the validity of approaches that
      model reductions in disability burden. A powerful treatment to relieve depression
      and prevent relapse is needed.

PMID- 11967455
TI  - Antidepressant treatment for depression: total charges and therapy duration*
AB  - BACKGROUND: The economic costs of depression are significant, both the direct
      medical costs of care and the indirect costs of lost productivity. Empirical
      studies of antidepressant cost-effectiveness suggest that the use of selective
      serotonin reuptake inhibitors (SSRIs) may be no more costly than tricyclic
      antidepressants (TCAs), will improve tolerability, and is associated with longer
      therapy duration. However the success of depression care usually involves
      multiple factors, including source of care, type of care, and patient
      characteristics, in addition to drug choice. The cost-effective mix of
      antidepressant therapy components is unclear. AIMS OF THE STUDY: Our study
      evaluates cost and antidepressant-continuity outcomes for depressed patients
      receiving antidepressant therapy. Specifically, we determined the impact of
      provider choice for initial care, concurrent psychotherapy, and choice of SSRI
      versus TCA-based pharmacotherapies on the joint outcome of low treatment cost and
      continuous antidepressant therapy. METHODS: A database of private health
      insurance claims identifies 2678 patients who received both a diagnosis of
      depression and a prescription for an antidepressant during 1990-1994. Patients
      each fall into one of four groups according to whether their health care charges
      are high versus low (using the median value as the break point) and by whether
      their antidepressant usage pattern is continuous versus having discontinued
      pharmacotherapy early (filling fewer than six prescriptions). A bivariate probit
      model controlling for patient characteristics, co-morbidities, type of depression
      and concurrent treatment is the primary multivariate statistical vehicle for the
      cost-effective treatment situation. RESULTS: SSRIs substantially reduce the
      incidence of patients discontinuing pharmacotherapy while leaving charges largely
      unchanged. The relative effectiveness of SSRIs in depression treatment is
      independent of the patient's personal characteristics and dominates the
      consequences of other treatment dimensions such as seeing a mental health
      specialist and receiving concurrent psychotherapy. Initial provider specialty is
      irrelevant to the continuity of pharmacotherapy, and concurrent psychotherapy
      creates a tradeoff through reduced pharmacotherapy interruption with higher
      costs. DISCUSSION: Longer therapy duration is associated with SSRI-based
      pharmacotherapy (relative to TCA-based pharmacotherapy) and with concurrent
      psychotherapy. High cost is associated with concurrent psychotherapy and choice
      of a specialty provider for initial care. In our study cost-effective care
      includes SSRI-based pharmacotherapy initiated with a non-specialty provider.
      Previous treatment history and other unobserved factors that might affect
      antidepressant choice are not included in our model. IMPLICATIONS FOR HEALTH CARE
      PROVISION: The decision to use an SSRI-based pharmacotherapy need not consider
      carefully the patient's personal characteristics. Shifting depressed patients'
      pharmacotherapy away from TCAs to SSRIs has the effect of improving outcomes by
      lowering the incidence of discontinuation of pharmacotherapy while leaving
      largely unchanged the likelihood of having high overall health care charges.
      Targeted use of concurrent psychotherapy may be additionally cost-effective.
      IMPLICATIONS FOR HEALTH POLICIES: The interaction of various components of
      depression care can alter the cost-effectiveness of antidepressant therapy. Our
      results demonstrate a role for the non-specialty provider in initiating care and
      support increased use of SSRIs as first-line therapy for depression as a way of
      providing cost-effective care that is consistent with APA guidelines for
      continuous antidepressant treatment. IMPLICATIONS FOR FURTHER RESEARCH: Further
      research that improves our understanding of how decisions regarding provider
      choice, concurrent psychotherapy, and drug choice are made will improve our
      understanding of the effects treatment choices on the cost-effectiveness of
      depression care. We have suggested that targeted concurrent psychotherapy may
      prove to be cost-effective; research to determine groups most likely to benefit
      from the additional treatment would further enable clinicians and healthcare
      policy makers to form a consensus regarding a model for treating depression.

PMID- 11967456
TI  - The civilian labor market experiences of Vietnam-era veterans: the influence of
      psychiatric disorders.
AB  - BACKGROUND: Most research on the civilian labor market experiences of veterans
      has focused on the extent to which the skills and experience acquired in the
      military are rewarded in the civilian employment sector. While studies have been
      mindful of the need to analyze this question in a multivariate framework,
      controlling for other factors that might independently affect labor market
      outcomes, they have met this goal with limited success. As a result, an important
      element of the employment and wage determination process - psychiatric health -
      has been absent from this literature. AIMS OF THE STUDY: Using a nationally
      representative survey of Vietnam-era veterans, this study analyzes the
      contribution of psychiatric health toward explaining differences in the post
      service civilian wages, hours worked, and employment probabilities among male
      veterans. METHODS: The analysis is based on data from the National Survey of the
      Vietnam Generation, a survey, completed in the late 1980s, of persons who were on
      active duty during the years of the Vietnam War, 1964-1975. Three outcome
      variables are studied - the hourly wage rate, usual hours worked per week, and a
      0-1 indicator for whether the respondent is currently working. Lifetime diagnoses
      of four categories of mental disorders - major depression, anxiety disorders,
      substance abuse/dependence, and combat-related posttraumatic stress disorder
      (PTSD) - were constructed from the US NIMH Diagnostic Interview Schedule,
      administered by the survey. The employment probability equation was estimated
      using probit; the hourly earnings and hours worked equations via ordinary least
      squares conditioned on being employed. RESULTS: The study finds that PTSD
      significantly lowered the likelihood of working and, for those veterans who were
      working, their hourly wages. On average, a veteran with a lifetime diagnosis of
      PTSD was 8.5 percentage points less likely to be currently working than was a
      veteran who did not meet diagnostic criteria. Among those who were employed,
      veterans with PTSD earned, on average, $2.38 less per hour ($3.61 in 1999 U.S.
      dollars). Anxiety disorders and major depression had nearly as large an effect on
      employment rates, as did PTSD. Major depression was also found to have lowered
      hourly wages by an average of $6.77 per hour ($10.17 in 1999 US dollars).
      However, psychiatric health did not affect typical hours worked per week.
      DISCUSSION: This study contributes new information to several literatures.
      Previous research on the extent to which PTSD interferes with readjustment to
      civilian life has focused on quality-of-life outcomes such as overall well-being,
      physical health, and homelessness. Previous research on mental health and
      earnings has focused on annual earnings. This study makes hourly wage
      comparisons, a closer measure of productivity differences since they represent
      differences in pay for the same input of time. Finally, this study demonstrates
      that the effects of psychiatric health are as important as the influence of non
      health characteristics that are thought to signal earnings potential in the
      civilian labor market (education and experience). These findings, however, may
      not apply generally. The importance of PTSD may be specific to veterans of the
      Vietnam War and may not pertain to persons suffering non-combat-related PTSD.
      IMPLICATIONS FOR HEALTH CARE PROVISION AND USE AND HEALTH POLICY FORMULATION: The
      magnitude of our estimates implies potentially large benefits from developing
      effective treatments for PTSD and from insuring access to these treatments.
      IMPLICATIONS FOR FURTHER RESEARCH: Future research should examine the
      relationship between work and PTSD in the general population and should explore
      the indirect effects of mental health, such as its effects on the post-service
      educational attainment and occupational choices of veterans.

PMID- 11967457
TI  - State parity legislation and changes in health insurance and perceived access to
      care among individuals with mental illness: 1996-1998*
AB  - BACKGROUND: The 1990's witnessed a new wave of state and federal legislation
      affecting mental health insurance in the United States. Although patient advocacy
      groups have hailed the passage of numerous "parity" laws that require insurance
      coverage for mental illnesses to equal that for physical ailments, it is unclear
      whether this activity represents a major improvement in insurance benefits among
      mentally ill or significantly increases their access to care. AIMS: This paper
      contrasts how insurance coverage has changed among individuals with mental health
      problems in states with and without parity legislation. METHODS: National survey
      data from 1996 to 1998, subset to a panel of 1220 individuals exceeding clinical
      screeners for a mental health disorder. Dependent variables are change in
      insurance status, insurance generosity and perception of access to care. The
      analysis contrasts changes in dependent variables between states with and without
      parity legislation (a difference-in-differences analysis). RESULTS: There are no
      statistical significant effects of state parity; point estimates suggest that
      parity mandates are associated with a slightly higher number of mentally ill
      reporting improved insurance generosity and access to care, but also with a
      higher number of mentally ill losing all insurance coverage in parity states. The
      estimated effects are too small to be statistically significant, although the
      sample size is limited and the study had only good statistical power to detect
      large effects. DISCUSSION: At the population level, state parity legislation
      appears to have not had large effects on the insurance coverage of the group that
      was intended as the primary beneficiary of legislation. Likely reasons include
      the limited scope of the actual legal requirements and large numbers of mentally
      ill that are not covered by health insurance subject to such legislation. The
      results do not exclude the possibility that some subgroups experienced
      substantial improvements in their insurance coverage. At the population level,
      large effects experienced by small subgroup are diluted by groups that
      experienced no similar changes. However, parity legislation was not considered a
      minor issue by advocates and opponents and this analysis has the statistical
      power to detect the sizeable differences that were argued in the policy debate.
      IMPLICATIONS FOR HEALTH POLICIES: While state parity legislation may have
      improved insurance benefits for some, it appears not to have resulted in
      substantial improvements for the mentally ill as a whole. The results could be
      very different, however, if strong federal legislation were passed that has a
      broader scope than state legislation. IMPLICATIONS FOR RESEARCH: The parity
      debate provides an important reminder of how little research is available to
      inform policy. This study provides a crude picture, but it is far from being a
      conclusive evaluation. The most urgent need is for data that continue to track
      changes in markets and policies.

PMID- 11967458
TI  - Assessing state parity legislation* 
AB  - The temptation is great, but premature, to conclude from the Sturm study that
      parity mandates had no effect on access and insurance coverage for the mentally
      ill. The study lacks statistical power for those directly covered by the
      mandates, and it is unlikely adequate power exists for those only indirectly
      affected. The inclusion of the uninsured, Medicaid enrollees, and privately
      covered individuals not subject to the mandates, and the imprecise outcome
      measures, increase the likelihood that other factors dominate parity. The timing
      of implementation in some states is also problematic. But Sturm asks the right
      questions and future waves of the Healthcare for Communities survey and other
      data will be better able to address them.arkets and policies.

PMID- 11967459
TI  - Editorial.

PMID- 11967460
TI  - An Economic Analysis of Psychotherapy for Borderline Personality Disorder
      Patients.
AB  - BACKGROUND: BPD is a serious mental illness in which psychotherapy has been shown
      to improve patient outcomes and reduce the use of health services. In most
      studies of psychotherapy, lower use of health services has been taken to imply
      lower health service costs. However, the costs of psychotherapy can offset any
      cost savings due to reduced use of other health services. AIMS OF THE STUDY: To
      estimate the net costs of health service use in a group of BPD patients receiving
      intensive psychotherapy. METHODS: Data on use of inpatient hospital, emergency
      hospital, ambulatory care, diagnostic tests and medications were collected for
      the twelve months before psychotherapy and the twelve months after the completion
      of treatment. Cost estimates were developed using standardised unit costs.
      RESULTS: There was a saving of approximately $670,000 in health service use over
      the thirty patients compared to a cost of $130,000 for psychotherapy, giving a
      net cost saving of $18,000 per patient. Most of this was due to reduced hospital
      admissions. Cost saving was higher in those patients who were high users of
      hospital services. Sensitivity analyses were performed; overall, the findings
      consistently show a reduction in the cost of health services used. DISCUSSION:
      The group studied consisted of 30 patients and comprised a before/after design.
      Therefore it does not overcome criticisms of other work in this area, that is of
      observational studies and small sample sizes. Nonetheless, the results were based
      on detailed costing of service use, using conservative assumptions and subject to
      sensitivity analysis. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The use of
      intensive psychotherapy in BPD patients who are high users of health services,
      particularly those who have had multiple hospital admissions, is probably
      warranted until more evidence is available. IMPLICATIONS FOR HEALTH POLICIES:
      There is little rigorous evidence on the effectiveness and cost-effectiveness of
      psychotherapy. BPD patients appear to generate high service costs so it is
      important to establish effective and cost-effective modes of treatment.
      IMPLICATIONS FOR FURTHER RESEARCH: Further research is warranted to establish
      accurate patterns of service use in BPD patients, and to identify those groups
      who will most benefit from intensive psychotherapy. erans.

PMID- 11967461
TI  - South African Mental Health Process Indicators.
AB  - BACKGROUND: In post-apartheid South Africa the organisation and delivery of
      mental health care is undergoing significant change. With the heritage of an
      under-resourced, fragmented, racially inequitable service, heavily reliant on
      chronic custodial treatment in large centralised institutions, this change is
      long overdue. New policy has set out a vision for a community-based,
      comprehensive, integrated mental health service. In order to realise this vision
      a review is required of the way in which care is currently delivered, or the
      'process' of mental health care. To date, no national research has been conducted
      regarding process of care indicators in South African mental health services.
      AIMS OF THE STUDY: This study documents four public sector mental health service
      process indicators in South Africa: bed occupancy rates, admission rates, average
      length of stay and default rates. METHODS: A questionnaire was distributed to
      provincial mental health co-ordinators, requesting numbers of occupied and
      available beds in psychiatric inpatient facilities, annual mental health
      admissions, average length of stay (ALOS), and default rate in ambulatory care
      settings. The information was supplemented by consultations with mental health co
      ordinators in each of the 9 provinces. RESULTS: The national bed occupancy rate
      is 83% (range: 63-109%). The national annual rate of admission to psychiatric
      inpatient facilities is 150 per 100 000 population (range: 33-300). The national
      average length of admission is 219 days in psychiatric hospitals, 11 days in
      general regional hospitals and 7 days in general district hospitals. On average
      11% of psychiatric patients who attend ambulatory care services on a monthly
      basis fail to keep their appointments. DISCUSSION: Although the national mean bed
      occupancy is compatible with international figures, there is considerable
      discrepancy between provinces, indicating both over- and under- utilisation of
      inpatient resources. Admission rates are low, relative to developed countries,
      though comparable to developing countries. Low admission rates are associated
      with a range of factors including inadequate service provision, unmet need,
      inaccessible services, cross-border flow between provinces and custodial patterns
      of care. There is evidence of long periods of admission relative to international
      settings. There is also considerable diversity between provinces, with certain
      institutions continuing to provide long term custodial patterns of care. Default
      rates are low relative to international settings and past reports default in
      South Africa. IMPLICATIONS FOR HEALTH POLICIES: In keeping with current policies
      there is an urgent need for local level evaluation and reform of chronic
      custodial care. The ongoing monitoring of process indicators is important in the
      transition to community-based mental health care. IMPLICATIONS FOR FURTHER
      RESEARCH: Limitations of the data, and problems of collecting information on
      mental health care within an integrated health system indicate the need for
      further research in this area. There is also a need for further research into
      unmet need for mental health care in South Africa.

PMID- 11967462
TI  - Cost-Shifting from Private to Public Payers: The Scene Before Parity Legislation.
AB  - BACKGROUND: Analyses that have been conducted previously on the implications of
      parity have focused on the concern that mental health costs of private payers
      will substantially increase. A complete analysis of the cost implications of
      parity, however, also needs to consider whether the mental health costs of public
      payers may increase particularly if employers or private insurers attempt to
      extrude enrollees with severe mental illness. This study examines the extent of
      mental health cost shifting from private to public payers during two separate two
      year periods prior to the implementation of parity legislation. The results of
      the analyses can serve as a necessary baseline against which the consequences of
      parity legislation on this direction of cost-shifting can be examined. METHODS:
      The study utilizes an all payer data set that contains information on the use of
      specialty mental health services (excluding private practitioners) by adults in
      an urban and a rural county in New York State. For each year of two time periods 
      1991/1992 and 1995/ 1996 - consumers were classified into payer groups based on
      whether their services were paid for by "Private Only", "Public Only",
      "Private/Public", "Self Pay" or "Other" payers. The proportion of individuals who
      moved from one payer group to another from one year to the following year of each
      time period and the average yearly costs under these payers were examined.
      Logistic regression models were used to identify the characteristics of persons
      most likely to remain with Private Only Payers in contrast to those likely to
      shift to Private/Public Only payers or to Public Only Payers. RESULTS: In both
      two-year time periods, the percent of persons who shifted in one year from
      Private Only to either Private/Public or Public Only payers was small. In
      contrast, a person in the Private/Public group has more than a 12 percent
      likelihood of shifting to a Public Only payer in the subsequent year. The average
      annual costs of the Private/Public group were higher than that of any other payer
      group. The average annual costs of persons who shifted into the Private/Public
      group from any other payer group or remained there from the previous year were
      even higher. The logistic regression analyses for both time periods showed that
      persons who shifted from Private Only to Private/Public or Public Only payers in
      contrast to those who remained with Private Only payers were more likely to have
      subsidized incomes, be younger and have a mental health disability. In 1995, the
      likelihood of the shift was also increased for those who were nonwhite and/or had
      a substance abuse disability. IMPLICATIONS: This study has found that individuals
      rarely shift directly from private payers to public payers. Rather, they first
      shift to having services reimbursed by both private and public payers, and during
      this period their average total service costs are extremely high. Persons who
      shift from private payers to having at least some of their services paid by
      public payers in subsequent years appear to be either young employees or young
      dependents who have severe mental illness or mental illness disabilities. Abusing
      substances and/or being nonwhite also increase the likelihood of a shift to
      public payers. Along with parity mandates, there has been an increase in managed
      care controls. The extent to which these controls will be used to accelerate the
      movement of these high cost persons from private to public payers needs close
      watch.

PMID- 11967463
TI  - Symptom Effects on Employment in a Structural Model of Mental Illness and
      Treatment: Analysis of Patients with Schizophrenia.
AB  - BACKGROUND: There is a long tradition in the health and mental health economics
      literatures of estimating the impacts of disorders on employment and earnings.
      Several analyses have associated mental illness with poorer labor market
      outcomes, often using indicators of disorders to measure mental illness, but it
      is unclear to what extent unobserved medical treatment biases the estimated
      impacts of disorders on labor market outcomes. In this study we argue that in
      order to judge the true employment costs of mental illness and the potential
      benefits of treatment it is necessary to account for the structural relationship
      between treatment, symptoms, and employment outcomes. AIMS OF THE STUDY: The
      study proposes a structural model for understanding mental illness impacts on
      employment and empirically estimates one element of this structural model that
      links symptoms of schizophrenia to patients' employment status. In addition, we
      use our empirical estimates to simulate employment consequences of more effective
      treatment and reductions in symptom levels. EMPIRICAL METHODS: Our empirical
      analyses use a sample of 1,643 adults with a schizophrenia diagnosis. We predict
      the likelihood of three outcomes - not employed, employed in a sheltered or
      supported job, and employed in a non-supported job. Analyses include measures of
      demographic characteristics, illness history, location differences, and detailed
      symptom measures. RESULTS: We find that negative symptoms have a substantial
      adverse impact on participation in both non-supported jobs and in sheltered or
      supported jobs. The impacts on employment of other symptoms of schizophrenia are
      not as large, but significant effects are also found for symptoms of depression.
      Simulations suggest, however, that only one-third of consumers would be employed
      in any type of job even given a large reduction in symptom levels. DISCUSSION:
      Negative symptoms are particularly important for role functioning and employment.
      The marginal effect on employment of a reduction in negative symptoms is several
      times greater than the effect of a comparable reduction in positive symptoms.
      Moreover, the effect of an improvement in symptoms on employment is stronger for
      non-supported employment than for working in sheltered or supported employment.
      Although commonly measured symptoms of schizophrenia impact employment, greater
      control of symptoms alone is unlikely to lead to large increases in employment
      for persons with schizophrenia in the near term. IMPLICATIONS FOR HEALTH CARE
      PROVISION AND USE: These findings suggest that improved treatment that results in
      reduced symptom levels will increase rates of employment among persons with
      schizophrenia, but that large employment impacts probably also require more
      effective rehabilitative therapies that target improvement in functioning.
      IMPLICATION FOR POLICY: Expansions of supported employment opportunities and
      removal of work disincentives in public income-support programs are two
      additional measures that may help to increase employment participation.

PMID- 11967464
TI  - Minority Response to Health Insurance Coverage for Mental Health Services.
AB  - BACKGROUND: To promote access to mental health services, policy makers have
      focused on expanding the availability of insurance and the generosity of mental
      health benefits. Ethnic minority populations are high priority targets for
      outreach. However, among persons with private insurance, minorities are less
      likely than whites to seek outpatient mental health treatment. Among those with
      Medicaid coverage, minorities continue to be less likely than whites to use
      services. AIMS OF THE STUDY: The present study sought to determine if public
      insurance is as effective in promoting outpatient mental healthtreatment as
      private coverage for ethnic minority groups. METHODS: The analysis uses data from
      the 1987 National Medical Expenditure Survey to model mental health expenditures
      as a function of minority status and private insurance coverage. An interaction
      term between the two highlights any differences in response to private and public
      insurance coverage. The analysis uses a two stage least squares method to account
      for endogeneity of insurance coverage in the model. RESULTS: Minorities are less
      responsive to private insurance than whites in two ways. First, minorities are
      less responsive to private insurance than to public insurance whereas whites do
      not show this difference. Second, minorities are less responsive to private
      insurance than whites are to private insurance. DISCUSSION: Results suggest that
      there is a difference in the effectiveness of public and private health insurance
      to encourage use of mental health services. Among minorities but not among
      whites, those with private coverage used fewer mental health services than those
      with public coverage. Minorities were not only less responsive to private
      insurance than public insurance, but among those who were privately insured,
      minorities used fewer mental health services than whites. These results imply
      that insurance may not be as effective a mechanism as hoped to encourage self
      initiated treatment seeking particularly among minority and other low income
      populations. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: These results
      suggest that increasing private insurance coverage to minority populations will
      not eliminate racial and ethnic gaps in professional help-seeking for outpatient
      mental health care. Although the total number of people receiving treatment might
      increase, these results suggest that whites would seek care in greater numbers
      than minorities and the size of the minority-white differential might grow.
      IMPLICATIONS FOR FURTHER RESEARCH: Areas for further research include the impacts
      of alternative definitions of mental health services, the dynamics of the
      substitution of inpatient for outpatient mental health care, elucidation of
      nonfinancial barriers to care for minorities, and determinants of timely help
      seeking among minorities.

PMID- 11967465
TI  - Editorial.

PMID- 11967466
TI  - How do Trends for Behavioral Health Inpatient Care Differ from Medical Inpatient
      Care in U.S. Community Hospitals? 
AB  - BACKGROUND: Inpatient care in the United States accounts for one third of the
      health care expenditures. There exists a well-established trend towards fewer
      inpatient admissions and shorter lengths of stay for all inpatient care, which
      can be attributed to cost containment efforts through managed care and advances
      in treatment technologies. However, different illnesses may not necessarily share
      the same pattern of change in inpatient care utilization. In particular, mental
      health and substance abuse (MHSA) care has experienced a particularly dramatic
      growth of specialized managed behavioral organizations, which could have led to
      an even faster decline. AIMS OF THE STUDY: This study contrasts the trends of
      MHSA inpatient care in U.S. community hospitals with medical inpatient care over
      the years 1988 to 1997. It also analyzes the trends for subgroups of MHSA stays
      by diagnostic groups, age and primary payer. METHODS: We use the National
      Inpatient Sample (NIS) from the Health Care Cost and Utilization Project (HCUP)
      to estimate both number of inpatient discharges per 1,000 population and average
      length of stay over the years and relate the two indices. Inpatient MHSA stays
      are categorized into subgroups by age, primary payer of the care, and diagnostic
      group. We use the Clinical Classification Software (CCS) to distinguish between
      affective disorders, schizophrenia and related disorders, other psychoses,
      anxiety and related disorders, pre-adult disorders, and alcohol-, substance-
      related mental disorders and other mental disorders. Trends of population
      adjusted discharges and length of stay were tested using a weighted least squares
      method. RESULTS: Population-adjusted MHSA discharges from community hospitals
      increased by 8.1% over the study period, whereas discharges for all conditions
      decreased. Within MHSA discharges, the 20-39 and 40-64 age groups experienced
      significant increase relative to other age group; the increase was particularly
      high for affective and psychotic disorders, which are only partially offset by a
      decrease for other diagnostic groups. Hospitalization for both MHSA and medical
      conditions displayed trends towards shorter lengths of stay, but with the decline
      for MHSA stays steeper (40%) than for all stays (21%). The reduction in length of
      stay not only applied to the privately insured, for which managed behavioral
      health care had the highest penetration rate, but held for all other payers as
      well, although the rate of decline is higher for private insurance than for other
      insurance. Inpatient stays with pre-adult disorders displayed the greatest
      percentage decline for both population-adjusted discharges and average length of
      stay. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Different pattern of
      utilization emerged for MHSA inpatient care as compared to hospitalization for
      all medical care over the years 1988-97. The more rapid decline in length of stay
      for MHSA stays than for all stays may have been a result of greater incentive for
      cost containment and therefore more intensive care management, and advances in
      treatment technology, especially medication. However, the fast decline in length
      of stay may also have led to repeat hospitalization as a result of premature
      discharges for patients with affective or psychotic disorders. Some financial
      incentives, such as case-rates or DRG-type payments to hospitals could have
      contributed to such adverse effects. Increases in discharges for severe disorders
      could also be a consequence of shifts from long-term facilities (for which no
      comparable data are available) to community hospitals, although the largest
      absolute and relative increases were for affective disorders rather than
      schizophrenia or other psychoses, the two disease subgroups that make up the
      majority of the institutionalized patients. International comparisons, assisted
      by new data, may help disentangle the effect of institutional change and that of
      development in treatment technology or practice pattern.

PMID- 11967467
TI  - Estimating Determinants of Multiple Treatment Episodes for Substance Abusers.
AB  - BACKGROUND: Health services researchers have increasingly used hazard functions
      to examine illness or treatment episode lengths and related treatment utilization
      and treatment costs. There has been little systematic hazard analysis, however,
      of mental health/substance abuse (MH/SA) treatment episodes. AIMS OF THE STUDY:
      This article uses proportional hazard functions to characterize multiple
      treatment episodes for a sample of insured clients with at least one alcohol or
      drug treatment diagnosis over a three-year period. It addresses the lengths and
      timing of treatment episodes, and the relationships of episode lengths to the
      types and locations of earlier episodes. It also identifies a problem that occurs
      when a portion of the sample observations is aepossibly censored. Failure to
      account for sample censoring will generate biased hazard function estimates, but
      treating all potentially censored observations as censored will overcompensate
      for the censoring bias. METHODS: Using insurance claims data, the analysis
      defines health care treatment episodes as all events that follow the initial
      event irrespective of diagnosis, so long as the events are not separated by more
      than 30 days. The distribution of observations ranges from 1 day to 3 years, and
      individuals have up to 10 episodes. Due to the data collection process,
      observations may be right censored if the episode is either ongoing at the time
      that data collection starts, or when the data collection effort ends. The
      Andersen-Gill (AG) and Wei-Lin-Weissfeld (WLW) estimation methods are used to
      address relationships among individuals multiple episodes. These methods are then
      augmented by a probit censoring model that estimates censoring probability and
      adjusts estimated behavioral coefficients and related treatment utilization and
      treatment costs. There has been little systematic hazard analysis, however, of
      mental health/substance abuse (MH/SA) treatment episodes. RESULTS: Five sets of
      variables explain episode duration: (i) individual; (ii) insurance; (iii)
      employer; (iv) binary, indicating episode diagnosis, location, and sequence; and
      (v) linkage, relating current diagnoses to previous diagnoses in a sequence.
      Sociodemographic variables such as age or gender have impacts at both the
      individual and at the firm level. Coinsurance rates and deductibles also have
      impacts at the individual and the firm levels. Binary variables indicate that
      surgical/outpatient episodes were the shortest, and psychiatric/outpatient
      episodes were the longest. Linkage variables reveal significant impacts of prior
      alcoholism, drug, and psychiatric episodes on the lengths of subsequent episodes.
      DISCUSSION: Health care treatment episodes are linked to each other both by
      diagnosis and by treatment location. Both the AG and the WLW models have merit
      for treating multiple episodes. The AG model permits more flexibility in
      estimating hazards, and allows researchers to model impacts of prior diagnoses on
      future episodes. The WLW model provides a convenient way to examine impacts of
      sociodemographic variables across episodes. It also provides efficient pooled
      estimates of coefficients and their standard errors. LIMITATIONS: The insurance
      claims data set covers 1989 through 1991, predating current managed care plans.
      It cannot identify untreated substance abusers, nor can it identify those with
      out-of-plan use. It provides treatment information only if services are covered
      by the insurance plan and are defined with a substance abuse diagnosis code. Like
      medical records, insurance claims will not specify substance abuse treatment
      received within the context of other health care (and thus identified by a non
      substance abuse diagnosis code) or community services. IMPLICATIONS FOR POLICY
      AND RESEARCH: This article characterizes multiple health treatment episodes for a
      sample of insured clients with at least one alcohol or drug treatment diagnosis
      within a three-year period. We identify both individual and employer effects on
      episode length. We find that episode lengths vary by the diagnosis type, and that
      the lengths (and by inference cost and utilization) may depend on the treatments
      that occurred in previous episodes. We also recognize that health care or illness
      episodes may be ongoing at times of health care events prior to the ends of data
      collection periods, leading to uncertain episode lengths. Corresponding estimates
      of costs or utilization are also uncertain. We provide a method that adjusts the
      episode lengths according to the probability of censoring.

PMID- 11967468
TI  - Scale, Efficiency and Organization in Norwegian Psychiatric Outpatient Clinics
      for Children.
AB  - BACKGROUND: It is generally believed that 5 percent of the population under 18
      years is in need of specialist psychiatric care. In 1998, however, services were
      delivered to only 2.1 percent of the Norwegian population. Access to services can
      be improved by increasing capacity, but also by increasing the utilization of
      existing capacity. Changing financial incentives has so far not been considered.
      Based on a relatively low number of registered consultations per therapist (1.1
      per therapist day) the ministry has stipulated that productivity should increase
      by as much as 50 percent. AIMS OF THE STUDY: Measuring productivity in
      psychiatric care is difficult, but we believe that studies of productivity should
      be an important input in policy making. The aim of this paper is to provide such
      an analysis of the productive efficiency of psychiatric outpatient clinics for
      children and youths, and in particular to focus on three issues: (i) is an
      increase in productivity of 50 percent a realistic goal, (ii) are there economies
      of scale in the sector, and (iii) to what extent can differences in productivity
      be explained by differences in staff-mix and patient-mix? METHODS: We utilize an
      approach termed Data Envelopment Analysis (DEA) to estimate a best-practice
      production frontier. The potential for efficiency improvement is measured as the
      difference between actual and best-practice performance, while allowing for trade
      offs between different staff groups and different mixes of service production.
      The DEA method gives estimates of efficiency and productivity for each clinic
      without the need for prices, and thus avoids the pitfalls of partial productivity
      ratios. The Kolmogorov-Smirnov statistic is used to compare efficiency
      distributions, providing tests of variable specification and scale properties.
      RESULTS: Based on 135 observations for the years 1997 to 1999, the tests lead to
      a model with two inputs, two outputs and variable returns to scale. The outputs
      are number of hours spent on direct and indirect interventions, while neither the
      number of interventions nor the number of patients was found to be significant.
      The inputs are the number of university-educated staff and other staff, but
      disaggregation of the latter group was not significant. The average of estimated
      clinic efficiencies is 71%. The mean productivity is 64%, but many large clinics
      have considerably lower performance due mainly to scale inefficiency. DISCUSSION:
      There seems to be considerable room for improved performance in these clinics. It
      is interesting that the potential is not that far from the officially stipulated
      goal of 50% increased productivity. Staff composition does matter for clinic
      performance, but the different groups do not have significantly different
      marginal productivities, indicating a lack of ability to utilize specialized
      skills. It should be noted that these results to some extent depend on the
      assumptions that medical practice is efficient, and that the available data
      accurately captures the activities of the clinics. IMPLICATIONS FOR FURTHER
      RESEARCH AND HEALTH POLICY: More appropriate outcome measures, e.g. global
      assessment of functioning scores (GAF), will soon be available and will improve
      the policy value of this type of analysis, as will a more refined data set with
      information about the number of personnel in training positions. The analyses in
      this paper indicate that a lack of consensus on the issues of who should be
      treated, how they should be treated and by whom results in large variations in
      productive efficiency. These issues are being debated in Norway, and it should be
      interesting to see whether this in itself leads to higher efficiency or whether a
      change in the incentive structure will be needed.

PMID- 11967470
TI  - Editorial.

PMID- 11967469
TI  - Comparing patients with depressive complaints and patients with chronic medical
      conditions on their functioning and medical consumption.
AB  - BACKGROUND: Several studies have found that depressive complaints are associated
      with limitations in functioning that are at least comparable with those of
      chronic medical conditions, such as diabetes or lung diseases. However, the
      consequences of these associations for the utilization of general health care
      services are not known, certainly not for health care settings outside the United
      States. AIMS OF THE STUDY: To investigate the association of depressive
      complaints with functioning and health care utilization, comparing this with the
      association of chronic medical conditions with functioning and health care
      utilization. METHODS: In a community-based sample of Dutch adults (N=9428),
      chronic conditions (21 types) and depressive complaints were assessed by self
      report. Only active conditions and depressive complaints, for which treatment was
      taking place, were selected for the analyses. Health status and disabilities were
      also assessed by self-report. Information on the utilization of health care
      services was based on self-report as well as on data extracted from a claims
      database. This database also provided information on the use of psychoactive
      medications. The associations between chronic conditions, depressive complaints
      and dependent variables were determined by analysis of variance or regression
      analysis, adjusting for possibly confounding factors (gender, age, living
      conditions). RESULTS: Depressive complaints, more than any chronic condition
      (except back problems), were associated with fatigue, poor subjective health and
      days spent in bed. Those having depressive complaints visited their general
      practitioner (GP) more often than the others. They also contacted a medical
      specialist more often than other patient categories, apart from patients with
      heart diseases. The combination of depressive complaints and chronic medical
      conditions was not associated with increased utilization or lower functioning.
      CONCLUSION: Depressive complaints are not only connected to functioning, but also
      to the utilization of general health care services. The strength of these
      associations is comparable with that of chronic medical conditions. This study
      stresses the pertinence of (research on) the management and treatment of patients
      with depressive complaints in general health care settings.

PMID- 11967471
TI  - Factors that influence the Cost of Deliberate Self-poisoning in Children and
      Adolescents.
AB  - BACKGROUND: Ideally, the type and quantity of services received by young people
      with mental health problems would be determined by need alone. In reality,
      however, a number of factors will influence resource-use, and thus the total cost
      of care. AIMS OF THE STUDY: The aim of this study was to evaluate the impact of
      baseline patient and family characteristics on the total cost of caring for
      children and adolescents who have deliberately poisoned themselves. It was
      hypothesised that the cost of this patient group would be associated with
      severity of suicidality and other psychiatric characteristics, the existence of
      current problems and demographic and socio-economic characteristics. METHODS:
      Univariate and multivariate regression analyses were used to examine the
      associations between baseline characteristics and both total statutory service
      costs and total NHS costs in 149 young people aged 16 years and under, referred
      to child mental health teams with a diagnosis of deliberate self-poisoning.
      RESULTS: Baseline variables found to be significantly associated with relatively
      more expensive care packages included a definite intention to die, the existence
      of current problems, being in foster care, poorer parental well being and not
      having a diagnosis of conduct disorder. No significant relationships were found
      between cost and measures of illness severity, including suicidal ideation,
      hopelessness and severity of depression. DISCUSSION: Although costs are not
      influenced by clinical measures of severity, service provision does appear to
      respond to more 'practical' notions of severity, such as intent to die and the
      existence of current problems. Some high-risk sub-groups, such as those with a
      conduct disorder and those who have experienced episodes of local authority care
      or accommodation, appear to be slipping through the health services net, although
      this may be due more to the demand-side problem of non-compliance than to issues
      of supply. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The evidence presented
      suggests that health care providers are directing more services towards those who
      are more in need, where need is defined in a practical rather than a clinical
      sense. More targeting of certain high-risk sub-groups may be needed, however,
      particularly those who are traditionally poor attenders and prone to drop-out.
      IMPLICATIONS FOR HEALTH POLICY FORMULATION: Interventions for young people who
      have attempted suicide should be better targeted towards high-risk groups, such
      as those with a diagnosis of conduct disorder. In addition, prevention schemes
      that target high-risk groups before a suicide attempt is made should be
      encouraged. IMPLICATIONS FOR FURTHER RESEARCH: This study is limited by small
      sample sizes. Research that focuses directly on the care of young people at high
      risk for repeat suicide attempts is needed, since the results presented here can
      be viewed only as exploratory and not explanatory.

PMID- 11967472
TI  - Substitution between Formal and Informal Care for Persons with Severe Mental
      Illness and Substance Use Disorders.
AB  - BACKGROUND: Persons with severe mental illness (SMI) often get extensive informal
      care from family members and friends as well as substantial amounts of formal
      treatment from paid professionals. Both sources of care are well documented, but
      very little is known about how one affects the other. AIMS OF THE STUDY: This
      analysis estimates the extent of substitution between direct care provided by
      family and friends and formal treatment for people with severe mental illness and
      substance use disorders. Separate estimates are generated for short-term and long
      term effects. METHODS: Data are from a randomized clinical trial conducted at
      seven mental health centers in New Hampshire between 1989 and 1995. The study
      includes detailed data for 193 persons with dual disorders measured at study
      entry and every six months for three years. Hours of informal care were compared
      with total treatment costs within each six-month period to measure short-term
      effects. Average amount of informal care over three years represented long-term
      caregiving practices. Measures of informal care are from interviews with informal
      caregivers. Treatment costs are based on combined data from management
      information systems, Medicaid claims, hospital records, and self reports. We used
      mixed effects repeated measures regression to estimate longitudinal effects and a
      multiple imputation technique to test the sensitivity of results to missing data.
      RESULTS: In the short-term, persons with bipolar disorder used significantly more
      formal care as informal care increased (complementarity). The relationship
      between short-term informal and formal care was significantly weaker for persons
      with schizophrenia. For both diagnostic groups there was a long-term substitution
      effect; a 4-6% increase in informal care hours was associated with an approximate
      1% decrease in formal care costs. DISCUSSION: Although they must be confirmed by
      further research, these findings suggest that there is a significant and strong
      relationship between care given by family and friends and that supplied by formal
      treatment providers. The analysis indicates that the short-term relationship
      between informal care and formal treatment tends to be complementary, but differs
      according to diagnosis. Long-term effects, which are possibly related to changing
      role perceptions, show substitution between the two forms of care. Missing data
      for family care hours in some time periods was a concern in this study. However,
      the consistency in results between the analyses that used imputed data and the
      model using only original data increase our confidence in the findings. Although
      there may be some endogeneity between formal and informal care in other treatment
      settings we believe the unique characteristics of the service-rich environment in
      which this study was conducted limit that concern here. IMPLICATIONS FOR HEALTH
      CARE PROVISION AND USE: The amount of care provided by informal caregivers has a
      significant impact on formal treatment costs. Models of care that explicitly
      acknowledge the interplay between the two types of care are needed to ensure
      efficient combinations of formal and informal care. IMPLICATIONS FOR HEALTH
      POLICY FORMULATION: How to best to encourage informal support, without
      overburdening caregivers, is a key challenge facing policy makers and providers
      of mental health services. The merits of various approaches to reducing caregiver
      burden is a subject that needs more attention from researchers. In the interim,
      the demands on informal caregivers may mount as efforts to reduce health care
      spending continue. IMPLICATIONS FOR FURTHER RESEARCH: Informal care is not often
      included in economic evaluations of mental health treatment. Although additional
      research is needed to understand better the mechanisms by which informal care and
      formal treatment are related, we believe our results offer a strong argument for
      including measures of informal care in future economic evaluations.

PMID- 11967473
TI  - A Cost-Effective Model for Increasing Access to Mental Health Care at the Primary
      Care Level in Nigeria.
AB  - BACKGROUND: Although effective treatment modalities for mental health problems
      currently exist in Nigeria, they remain irrelevant to the 70% of Nigeria's 120
      million people who have no access to modern mental health care services. The
      nation's Health Ministry has adopted mental health as the 9th component of
      Primary Health Care (PHC) but ten years later, very little has been done to put
      this policy into practice. Mental Health is part of the training curriculum of
      PHC workers, but this appears to be money down the drain. AIMS OF THE STUDY: To
      review the weaknesses and problems with existing mode of mental health training
      for PHC workers with a view to developing a cost-effective model for integration.
      METHODS: A review and analysis of current training methods and their impact on
      the provision of mental health services in PHC in a rural and an urban local
      government area in Nigeria were done. An analysis of tested approaches for
      integrating mental health into PHC was carried out and a cost-effective model for
      the Nigerian situation based on these approaches and the local circumstances was
      derived. RESULTS: Virtually no mental health services are being provided at the
      PHC levels in the two local government areas studied. Current training is not
      effective and virtually none of what was learnt appears to be used by PHC workers
      in the field. Two models for integrating mental health into PHC emerged from the
      literature. Enhancement, which refers to the training of PHC personnel to carry
      out mental health care independently is not effective on its own and needs to be
      accompanied by supervision of PHC staff. Linkage, which occurs when mental health
      professionals leave their hospital bases to provide mental health care in PHC
      settings, requires a large number of skilled staff who are unavailable in
      Nigeria. In view of past experiences in Nigeria and other countries, a mixed
      enhancement-linkage model for mental health in PHC appears to be the most cost
      effective approach for these Nigerian communities. DISCUSSION: Nigeria is
      currently experiencing a 'double epidemic', and with high infant and maternal
      mortality rates, the burden of mental health problems is still invisible to
      policy makers. Meagre resources allocated to mental health need to be utilised
      maximally with cost-effective interventions. This mixed enhancement-linkage model
      draws on the strengths of both models, while taking into account their
      limitations. Concrete conclusions cannot be drawn until the model developed is
      fully tested. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: This model has the
      potential of making mental health services available, accessible and acceptable
      in these communities. This should reduce the burden of suffering for the mentally
      ill by providing treatment and restorative care, promoting mental health and
      preventing mental illness in the populace. IMPLICATIONS FOR HEALTH POLICY
      FORMULATION: The current mental health policy for Nigeria focuses on enhancement
      as the mode in which mental health can be successfully integrated into PHC and so
      far this has not been successful. Results emerging from this model can be
      presented to policy makers thereby supporting replication in other parts of the
      country. This could ultimately lead to a change in the mental health policy on
      training for mental health at the PHC level. IMPLICATIONS FOR FURTHER RESEARCH:
      Mental health services and mental health economics research are still at the
      stage of infancy in Nigeria. This study provides baseline information and should
      stimulate further research in these two vital areas.

PMID- 11967474
TI  - Financial Burden and Out-of-Pocket Expenditures for Mental Health Across
      Different Socioeconomic Groups: Results from HealthCare for Communities.
AB  - BACKGROUND: Mental health benefits have traditionally been much less generous
      than benefits for physical health care, with separate deductibles, higher
      copayments or coinsurance, and lower limits on covered services, a trend that
      continues despite a recent wave of 'parity' legislation. In spite of the current
      policy debates on mental health insurance reforms, little is known about the
      burden of mental health out-of-pocket expenditures. AIMS OF THE STUDY: This study
      examines differences in out-of-pocket expenditures and their burden across
      different populations, stratified by insurance status, age, ethnicity, and
      socioeconomic groups. METHODS: This study uses the 1998 HealthCare for
      Communities household survey, the latest national survey data that are currently
      available, to measure the burden of out-of-pocket mental health expenditures. We
      use several measures of burden such as total out-of-pocket expenditures, their
      share of total treatment costs, and their share of family income. To address the
      methodological issues that arise in the calculation of the relative measures of
      burden (e.g. outliers, measurement error, systematic underreporting) we consider
      three different approaches that have been suggested in the literature and discuss
      their relative advantages given the type of data typically available. RESULTS:
      Although there is a common perception that out-of-pocket expenditures for mental
      health services represent a significant burden for service users, the estimates
      suggest that this is not the case. In fact, across the three measures of out-of
      pocket expenditures as a share of income the estimates are under 10 percent for
      most groups. However, there is some variation in burden across groups with people
      who are older, uninsured, or minority spending a larger share of their income out
      of-pocket. Since many insurance plans have limits on the number of visits covered
      and on the total amount that the insurer will pay for mental health services, the
      share of total mental health expenditures that are paid by individuals is another
      important measure of the burden faced by people with mental health service needs.
      We estimate that the mean out-of-pocket share of total expenditures for the group
      as a whole is 25 percent. In addition, we find that the burden varies across
      groups with older, more educated, or privately insured individuals paying a
      larger share of expenditures out-of-pocket. DISCUSSION: Although the overall
      picture regarding the burden of out-of-pocket costs relative to income is
      encouraging, it is also important to keep in mind that individuals make treatment
      decisions based on their available income. The fact that the burden of actual out
      of-pocket payments is relatively low may also reflect decisions to forego
      potentially valuable care. Nevertheless, the results for mental health do not
      suggest that out-of-pocket costs are currently a major burden for most users.
      This situation may reflect a major change from the past given the recent shifts
      towards managed care, however there are no comparable data available to test this
      hypothesis empirically. IMPLICATIONS FOR HEALTH POLICY FORMULATION AND FURTHER
      RESEARCH: It may be tempting to attribute the low estimates of out-of-pocket
      expenditures as a share of income in this paper to recent parity legislation.
      However, recent research shows that parity legislation has not led to significant
      changes in benefit design. In fact the high ratio of out-of-pocket payments
      relative to total mental health care expenditures presented in this paper are
      consistent with a limited role of parity legislation. Another possible
      explanation for the observed results is the growth of managed care and the shift
      in treatment style towards greater use of medications, which are comprehensively
      covered in most private insurance plans, has reduced total treatment costs and
      consequently the size of out-of-pocket payments.

PMID- 11967475
TI  - A review of the pharmacotherapy of adults with attention-deficit/hyperactivity
      disorder.
AB  - OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity
      disorder (ADHD) in adults, the use of pharmacotherapeutics remains less
      established. METHODS: A systematic review of the literature identified 15 studies
      (N = 435 subjects) of stimulants, and 22 studies of non-stimulant medications (N
      = 421 subjects) including antidepressants, antihypertensives, amino acids, and
      wake-promoting agents for the treatment of ADHD in adults. RESULTS: Studies with
      stimulants and antidepressants demonstrated significant short-term improvement in
      ADHD symptoms compared to placebo in adults. Methylphenidate (MPH) and
      amphetamine had an immediate onset of action whereas the ADHD response to
      pemoline and antidepressants appeared delayed. The response to amphetamine and
      MPH appears to be dose-dependent. Controlled data on nicotonic and noradrenergic
      compounds appear promising. There was considerable variability in diagnostic
      criteria, dosing parameters, and response rates between the various studies.
      CONCLUSIONS: Under controlled conditions, the aggregate literature shows that the
      stimulants and noradrenergic antidepressants had a clinically and statistically
      significant beneficial effect on treating ADHD in adults.

PMID- 11967477
TI  - Relationship between current quality of life and family of origin dynamics for
      college students with Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: This study examines the relationship between current quality of life,
      family of origin relationship dynamics, and the presence of Attention
      Deficit/Hyperactivity Disorder (ADHD) in college students. METHOD: Participants
      were 37 ADHD undergraduate college students and 59 non-ADHD undergraduate
      students. Participants completed a background information questionnaire, Quality
      of Life Questionnaire, Family Environment Scale, and the Family Adaption and
      Cohesion Scale II. RESULTS: In comparison to the control group, the ADHD group
      reported lower quality of life. The ADHD and non-ADHD groups did not differ
      significantly in reported family of origin relationship dynamics. Family of
      origin dynamics were highly predictive of current overall quality of life for the
      ADHD group, but less so for the non-ADHD group. CONCLUSION: The results of this
      study suggest that family of origin relationship dynamics deserve further study
      with respect to how they impact adult quality of life for individuals with ADHD.

PMID- 11967476
TI  - Cognitive functioning in adults with Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVES: Children with Attention-Deficit/Hyperactivity Disorder (ADHD) appear
      to be deficient in executive control. The purpose of this study was to determine
      if adults with ADHD are also deficient in executive control. METHOD: The
      performance of 18 adults with ADHD and 18 control subjects was compared on two
      tests of executive control, and two control tasks. The executive control tasks
      used in the study were the Trail Making Test (B), and the Tower of Hanoi. The
      control tasks used were the Trail Making Test (A), and the Benton Facial
      Recognition Test. RESULTS: The subjects with ADHD performed more poorly than did
      the normal controls on the executive control tasks. The subjects with ADHD,
      however, also performed more poorly on the Trail Making Test (A). CONCLUSIONS:
      The ADHD subjects showed a deficit in executive control, but this deficit was not
      confined to the executive control domain.

PMID- 11967478
TI  - The Assessment of Hyperactivity and Attention (AHA): development and preliminary
      validation of a brief self-assessment of adult ADHD.
AB  - A brief self-rating scale, the Assessment of Hyperactivity and Attention (AHA),
      was developed and validated using a "gold standard" DSM-based semi-structured
      interview. The sample consisted of 101 smokers (74% male, 73% Caucasian)-38.6%
      with no DSM-IV ADHD diagnosis, 10.9% with a childhood diagnosis only, and 50.5%
      with an adult diagnosis (requiring childhood diagnosis as well). The mean age SD
      was 33.7 9.7; participants smoked a mean of 19.0 5.6 cigarettes/day. Results
      indicate that the AHA has utility as a screening tool and as a self-report
      assessment of ADHD with sensitivity of .80, specificity of .60, positive
      predictive power of .67, negative predictive power of .75, kappa of .40, odds
      ratio of 6.15, and an area under the curve (receiver operating characteristic
      analysis) of .79. Given the high rate of ADHD among smokers, the AHA may be
      useful in identifying smokers who may need more in-depth clinical evaluation for
      attentional problems.

PMID- 11967480
TI  - Burnout in chairs of obstetrics and gynecology: diagnosis, treatment, and
      prevention.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of burnout
      in chairs of academic departments of obstetrics and gynecology, identify
      important stressors, and develop strategies to treat and prevent burnout. STUDY
      DESIGN: We performed a cross-sectional study of 131 chairs in the United States
      and Puerto Rico. We used a 6-part questionnaire focusing on demographics,
      potential stressors, satisfaction with personal and professional life, self
      efficacy, burnout as measured by the Maslach Burnout Inventory-Human Services
      Survey (MBI-HSS), and support from the spouse/partner and family. Statistical
      analyses were performed with the chi(2) test for categorical variables and t test
      or analysis of variance for continuous variables. RESULTS: Questionnaires were
      returned from 119 chairs, 110 men and 9 women, a response rate of 91%. Chairs had
      served an average of 7.2 years. They worked an average of 67.4 hours each week,
      spending 45% of their time in administrative duties, 31% in patient care, 15% in
      teaching, and 8% in research. Female chairs worked significantly more hours per
      week than male chairs, 76.9 versus 66.7 hours (P =.005). Chairs who had served
      >10 years worked significantly fewer hours each week than did those who had been
      chairs <5 years, 63.2 versus 69.2 hours (P =.04). The most significant stressors
      were hospital/departmental budget deficits, Medicare/Medicaid billing audits,
      loss of key faculty, union disputes, and faculty, resident, and staff dismissals.
      To deal with stress, chairs most often spent time with family and friends. Twenty
      two percent of chairs were somewhat-very dissatisfied with their positions. The
      MBI-HSS revealed a high subscale score for emotional exhaustion, moderate-high
      for depersonalization, and high for personal accomplishment. High emotional
      exhaustion was observed in younger chairs, those who worked nearly 70 hours each
      week, and those with less spouse/partner support. Burnout was more common in new
      chairs. CONCLUSION: Burnout in chairs of obstetrics and gynecology is
      characterized by a high level of emotional exhaustion, moderate-high
      depersonalization, and high personal accomplishment. These findings should be
      used to develop programs to improve the psychologic well-being of our academic
      leaders.

PMID- 11967481
TI  - Surgical skills assessment: a blinded examination of obstetrics and gynecology
      residents.
AB  - OBJECTIVE: We have previously shown that objective structured assessment of
      technical skills (OSATS) is an innovative, reliable, and valid method of
      assessing surgical skills. Our goal was to establish the feasibility,
      reliability, and validity of our surgical skills assessment instrument when
      administered in a blinded fashion. STUDY DESIGN: A 7-station OSATS was
      administered to 16 obstetric and gynecology residents from Madigan Army Medical
      Center. The test included laparoscopic (salpingostomy, intracorporeal knot, and
      ligation of vessels with clips) and open abdominal procedures (subcuticular
      closure, bladder neck suspension, enterotomy repair, and abdominal wall closure).
      All tasks were performed with lifelike surgical models. Residents were timed and
      assessed at each station with 3 methods of scoring: task-specific checklist,
      global rating scale, and pass/fail grade. Each resident was evaluated by one
      examiner blinded as to the postgraduate year level and one examiner who had
      previously worked with the resident. RESULTS: Assessment of construct validity
      (the ability to distinguish between resident levels) found significant
      differences on the checklist, global rating scale, and pass/fail grade by
      residency level for both blinded and unblinded examiners. Reliability indices
      calculated with Cronbach's alpha were.82 for the checklists and.93 for the global
      rating scale. Overall interrater reliability between blinded and unblinded
      examiners was 0.95 for global rating scale and ranged from 0.74 to 0.97 for the
      checklists. The cost to administer the exam for the 16 residents was
      approximately $1000. CONCLUSIONS: OSATS administered in either a blinded or
      unblinded fashion can assess residents' surgical skills with a high degree of
      reliability and validity. This study provides further evidence that OSATS can be
      used to establish surgical competence.

PMID- 11967482
TI  - Prevention of neonatal group B streptococcal disease: A combined intrapartum and
      neonatal protocol.
AB  - OBJECTIVE: We sought to assess the efficacy of a clinical protocol to reduce the
      incidence of early-onset neonatal group B Streptococcus (GBS) infection. STUDY
      DESIGN: We assessed neonatal sepsis from GBS and other organisms with use of a
      before-after study design to evaluate the effects of implementation of combined
      intrapartum antimicrobial prophylaxis given selectively to mothers with GBS risks
      and penicillin G given to all neonates. RESULTS: In 1994, early-onset GBS
      infection developed in 31 of 13,887 live births (2.2/1000), 13 preterm and 18
      term cases. After implementation of the prophylaxis protocol (1995), 6 of 13,527
      live births had early-onset GBS (0.4/1000) (P <.001). There were no preterm (P
      =.0004) and 6 term GBS cases (P =.02). The efficacy continued through 1999
      (0.5/1000) without an increase in neonatal infections from other bacteria.
      CONCLUSION: Combined maternal and infant antimicrobial prophylaxis can
      significantly and safely reduce rates of early-onset GBS infection in both
      preterm and term infants.

PMID- 11967483
TI  - Establishing a clinical program for human immunodeficiency virus 1-seropositive
      men to father seronegative children by means of in vitro fertilization with
      intracytoplasmic sperm injection.
AB  - OBJECTIVE: We assessed the safety and efficacy of providing assisted reproduction
      to men who are seropositive for human immunodeficiency virus type 1 (HIV-1).
      STUDY DESIGN: HIV-1-serodiscordant couples underwent in vitro fertilization with
      intracytoplasmic sperm injection (IVF-ICSI). Patients were screened for HIV-1 3
      and 6 months after embryo transfer to determine safety. Infants and mothers were
      tested at delivery and at 3 months after delivery. Clinical outcomes were
      compared with those of matched control couples who had undergone IVF-ICSI to
      measure efficacy. RESULTS: There were no seroconversions in women (n = 34) or
      offspring (n = 25) after 55 embryo transfers. Treatment efficacy was similar to
      that for control couples: retrieved eggs (15.8 +/- 1.3 vs 12.3 +/- 0.8);
      fertilization rate (64.9% vs 68.0%); embryos cryopreserved (1.1 +/- 0.3 vs 0.3 +/
      0.1, P <.05); clinical pregnancies per embryo transfer (45.5% vs 35.4%); ongoing
      or delivered pregnancies per embryo transfer (30.9% vs 25.0%). CONCLUSION:
      Although findings are preliminary, IVF-ICSI provides HIV-1-serodiscordant couples
      with a reasonably safe means of having children because their assisted
      reproduction performance is similar to that of conventional patients.

PMID- 11967484
TI  - Effect of cerclage on obstetrical outcome in twin gestations with a shortened
      cervical length.
AB  - OBJECTIVE: Our purpose was to determine the impact of cerclage placement on
      obstetric outcome in twin gestations with a shortened cervical length. STUDY
      DESIGN: A prospective cohort study of 147 consecutive twin pregnancies (July 1994
      to March 2001) who underwent transvaginal ultrasonographic cervical length
      measurement between 18 and 26 weeks' gestation. Cerclage was offered to women
      with cervical lengths < or = 25 mm. Patients were segregated into quartiles by
      cervical length. Regression analysis and chi(2) tests were used to determine the
      effect of cervical length and cerclage on parameters of prematurity. RESULTS: One
      hundred twenty-eight twin gestations met inclusion criteria, including 21 (16.4%)
      who underwent cerclage for a cervical length < or = 25 mm. Decreasing cervical
      length was significantly associated with a shorter length of gestation, lower
      combined birth weight, delivery at < or = 34 weeks, preterm premature rupture of
      fetal membranes, and very low birth weight. None of these outcomes was altered by
      cerclage placement. CONCLUSION: Midtrimester cerclage does not alter the risks of
      prematurity associated with a shortened cervical length in twin gestations.

PMID- 11967485
TI  - A comparison of amniotic fluid fetal pulmonary phospholipids in normal and
      diabetic pregnancy.
AB  - OBJECTIVE: Our purpose was to determine whether there are differences in the
      timing of the appearance of various amniotic fluid fetal pulmonary phospholipids
      in normal and diabetic pregnancy. STUDY DESIGN: A case-control study of 295
      subjects with diabetes and 590 control subjects was performed by use of
      gestational age-matched amniocentesis specimens analyzed for
      lecithin/sphingomyelin (L/S) ratio, phosphatidylinositol (PI), and
      phosphatidylglycerol (PG) composition. Diabetic subjects were stratified
      according to type of diabetes, degree of blood glucose control, and birth
      percentile of the neonate. RESULTS: There was no difference in L/S ratios over
      gestational age by type of diabetes or quality of glycemic control. Women with
      preexisting diabetes had significantly higher PI levels at 33 to 35 weeks'
      gestation, which became similar to levels of control subjects after 36 weeks,
      whereas patients with gestational diabetes mellitus and control subjects had
      similar PI levels throughout. In diabetic subjects, the onset of production of PG
      was delayed from 35.9 +/- 1.1 weeks (controls) to 38.7 +/- 0.9 weeks (overt
      diabetics) and 37.3 +/- 1.0 weeks for gestational diabetes mellitus (P <.001).
      The delay in PG synthesis was not related to infant sex, level of maternal
      glucose control, or fetal macrosomia. CONCLUSIONS: Fetal pulmonary maturation, as
      evidenced by the onset of PG production in the amniotic fluid, is delayed in
      diabetic pregnancy by 1 to 1.5 weeks. This delay appears to be associated with an
      early and sustained elevation in amniotic fluid PI levels at 32 to 34 weeks.

PMID- 11967486
TI  - Intrauterine progesterone treatment of early endometrial cancer.
AB  - OBJECTIVE: Our purpose was to assess the feasibility of using a progesterone
      containing intrauterine device (IUD) to treat presumed Federation Internationale
      Gynecologie et d'Obstetrique (FIGO) stage IA, grade 1 endometrioid cancer in
      women at high risk for perioperative complications. STUDY DESIGN: Candidates were
      women with American Society of Anesthesiologists class III or IV grade 1
      endometrioid cancer and no imaging evidence of myometrial invasion. Subjects
      underwent hysteroscopy, curettage, and IUD placement, followed by endometrial
      biopsy every 3 months for 1 year. The records of similar patients treated
      surgically during the 3 years before protocol initiation were reviewed for
      comparison. RESULTS: Sixteen patients fulfilled study criteria. Fourteen
      consented to participation; one was excluded at the time of IUD placement (grade
      2 disease identified) and one was lost to follow-up. Twelve subjects have been
      followed up to 36 months; results of biopsies were negative in 7 of 11 at 6
      months and 6 of 8 at 12 months. No IUD-related complications, except for
      expulsion, occurred. Sixteen complications (one fatal) occurred in 9 of the 15
      control patients. CONCLUSION: Intrauterine progesterone appears to eradicate some
      cases of presumed stage IA, grade 1 endometrioid cancer in women at high risk for
      perioperative morbidity.

PMID- 11967487
TI  - Effect of hypoxia on calcium influx and calcium/calmodulin-dependent kinase
      activity in cortical neuronal nuclei of the guinea pig fetus during development.
AB  - OBJECTIVE: Our purpose was to investigate the effect of hypoxia on calcium
      (Ca(++)) influx and Ca(++)-calmodulin (CaM)-dependent protein kinase IV (CaM
      kinase IV) activity in the neuronal nuclei of the guinea pig fetal cerebral
      cortex during development. STUDY DESIGN: Preterm and term pregnant guinea pigs (n
      = 61) were exposed to either 21% or 7% oxygen for 60 minutes. Hypoxia in the
      fetal cerebral cortical tissue was documented by determining the tissue
      concentrations of adenosine triphosphate (ATP) and phosphocreatine. Fetal
      cerebral cortical neuronal nuclei were isolated and purified, and ATP-dependent
      Ca(++) influx and CaM kinase activity were determined. RESULTS: Hypoxia resulted
      in increased neuronal intranuclear (45)Ca(++) influx for 2 minutes from 6.65 +/-
      1.29 pmol/mg protein to 9.07 +/- 1.98 pmol/mg protein (P <.05) in preterm and
      from 6.65 +/- 1.63 pmol/mg protein to 11.26 +/- 1.79 pmol/mg protein (P <.05) in
      term fetuses. The hypoxia-induced (45)Ca(++) influx was significantly higher (P
      <.05) in the term than in the preterm fetuses. Hypoxia resulted in increased CaM
      kinase IV activity from 383.7 +/- 53.3 pmol/mg/min protein to 451.6 +/- 59.5
      pmol/mg/min protein (P <.05) in the preterm and from 364.6 +/- 109.7 pmol/mg/min
      protein to 487.0 +/- 43.3 pmol/mg/min protein (P < 0.05) in term fetuses. No
      significant difference was observed in CaM kinase IV activity between the preterm
      and the term groups. CONCLUSION: Cerebral hypoxia increases calcium influx and
      CaM kinase IV activity in the cortical neuronal nuclei of the guinea pig fetal
      brain during development.

PMID- 11967489
TI  - Evaluation of endometrial polyps.
AB  - OBJECTIVE: Endometrial polyps are relatively common in all groups of women. More
      polyps are being diagnosed with the widespread use of transvaginal ultrasound
      scanning and sonohysterography. The reported incidence of malignancy is low. The
      potential benefit of a noninvasive technique to distinguish benign from malignant
      polyps is obvious. This study was undertaken to evaluate endometrial polyps by
      color flow Doppler ultrasound scanning and histopathologic examination. STUDY
      DESIGN: This was an observational study of patients with an endometrial polyp on
      sonohysterography who underwent interrogation of their polyp with color Doppler
      ultrasound scanning and subsequently polypectomy. Polyp volume, resistive index,
      pulsatility index, indication for scan (bleeding vs incidental), and patient age
      were correlated with histopathologic type of the polyp (nonfunctional,
      proliferative, secretory, hyperplastic, or malignant). RESULTS: Of 61 patients
      studied, 42 patients (68.9%) were scanned for abnormal bleeding, and 19 patients
      (31.1%) had their polyps discovered incidentally. There were no statistically
      significant differences between histologic categories and the resistive index,
      pulsatility index, or size of the polyp. The age of patients with nonfunctional
      polyps was significantly greater than any other group (P <.001). Ninety-four
      percent of the functional polyps were discovered because of abnormal bleeding;
      38% of the nonfunctional polyps were discovered incidentally (P <.001).
      CONCLUSION: The data suggest that the objective assessment of blood flow
      impedance (resistive index, pulsatility index) in endometrial polyps and the size
      of these polyps cannot replace surgical removal and pathologic evaluation to
      predict histologic type. Patients with nonfunctional polyps were older and less
      likely to have vaginal bleeding.

PMID- 11967488
TI  - Adenosine A(2A) receptors mediate hypoxic inhibition of fetal breathing in sheep.
AB  - OBJECTIVE: Hypoxia inhibits fetal breathing through activation of central
      adenosine (ADO) receptors that modulate fetal behavioral state. This study was
      designed to determine whether adenosine A(1) and/or A(2A)receptor subtypes
      mediate the depressant effects of hypoxia. STUDY DESIGN: In 14 chronically
      catheterized fetal sheep (>0.8 term), hypoxemia was induced by having the ewe
      breathe a gas mixture of 9% oxygen for 1 hour. During hypoxia, the fetus was
      infused intra-arterially with a vehicle or an antagonist for adenosine A(1) or
      A(2A) receptors. Statistical analysis was performed by using analysis of variance
      with Tukey's least significant difference criterion. RESULTS: Fetal isocapnic
      hypoxemia (PaO(2): control, approximately 24 mm Hg; hypoxia, approximately 14 mm
      Hg) virtually eliminated rapid eye movements and breathing when the fetus was
      infused with vehicle or the A(1) receptor antagonist. In contrast, adenosine
      A(2A) receptor blockade abolished the hypoxia-induced arrest of rapid eye
      movements and breathing. CONCLUSION: Hypoxic inhibition of rapid eye movements
      and breathing is critically dependent on activation of adenosine A(2A) receptors.

PMID- 11967490
TI  - Expression of a retinol dehydrogenase (hRoDH-4), a member of the retinol/steroid
      dehydrogenase family implicated in retinoic acid biosynthesis, in normal and
      neoplastic endometria.
AB  - OBJECTIVE: Retinoic acid plays an essential role in epithelial differentiation,
      and retinoid homeostasis is disrupted in cancers of epithelial origin. The goal
      of this study was to determine whether hRoDH-4, an enzyme that can catalyze the
      first and rate-limiting step in retinoic acid biosynthesis, is expressed in
      normal endometrium and, if so, whether its expression is altered in endometrial
      cancer. STUDY DESIGN: Proliferative, secretory, hyperplastic, and neoplastic
      endometria were examined by immunocytochemistry for hRoDH-4 protein and by
      reverse transcriptase-polymerase chain reaction for the hRoDH-4 transcript.
      RESULTS: In proliferative and secretory glandular epithelia, immunoreactive hRoDH
      4 was uniformly present. In endometrial cancers, hRoDH-4 immunoreactivity was
      markedly reduced in many neoplastic epithelial cells. Expression of hRoDH-4 in
      normal and neoplastic endometrium was confirmed by findings on reverse
      transcriptase-polymerase chain reaction. CONCLUSION: These findings are
      consistent with the hypothesis that altered expression of enzymes essential for
      in situ retinoic acid biosynthesis is an important phenotypic change associated
      with the development of endometrial cancer.

PMID- 11967491
TI  - In vitro maturation and fertilization of oocytes from unstimulated ovaries:
      predicting the number of immature oocytes retrieved by early follicular phase
      ultrasonography.
AB  - OBJECTIVE: To select women who will benefit most from in vitro maturation (IVM)
      of oocytes treatment, this study was undertaken to examine the ability of a
      transvaginal ultrasonography to predict the number of immature oocytes collected
      from unstimulated ovaries. STUDY DESIGN: The relationship between the number of
      immature oocytes retrieved and the pregnancy rate was assessed in 189 IVM
      treatment cycles. In 96 consecutive cycles, an early follicular phase
      transvaginal ultrasonographic measurement of the antral follicle count (AFC),
      ovarian volume, and peak ovarian stromal blood flow velocity (Vmax) was
      performed, and the results were correlated with the number of immature oocytes.
      RESULTS: The clinical pregnancy rate increased significantly with the number of
      oocytes retrieved (P =.02) and was 26.8% (15/56) in those with >10 immature
      oocytes. The AFC, ovarian volume, and ovarian stromal Vmax were all predictive of
      the number of oocytes retrieved, but when the other factors were controlled by
      multiple regression analysis the AFC was the only significant predictor (P
      <.001). CONCLUSIONS: Pregnancy rates after IVM correlate with the number of
      immature oocytes retrieved. This is best predicted by an ultrasonographic
      assessment of the AFC.

PMID- 11967492
TI  - Endometritis: the clinical-pathologic syndrome.
AB  - OBJECTIVE: The purpose of this study was to evaluate histologically proved
      endometritis as a clinical syndrome that is distinct from laparoscopically
      confirmed salpingitis. STUDY DESIGN: This was a cross-sectional study of 152
      women in an urban hospital with a suspected pelvic inflammatory disease. All
      women provided a standardized medical history and underwent physical examination,
      endometrial biopsy, and laparoscopy. We defined endometritis by the presence of
      plasma cells in endometrial stroma and neutrophils in the endometrial epithelium.
      RESULTS: Of 152 women who were enrolled, 43 women had neither endometritis nor
      salpingitis; 26 women had endometritis alone without salpingitis, and 83 women
      had salpingitis. Those women with endometritis alone more often had douched
      recently, had a current intrauterine device, and were in menstrual cycle day 1 to
      7, compared with women with no endometritis or salpingitis (P =.007,.04,.005,
      respectively) or women with acute salpingitis (P =.03,.01,.02, respectively).
      Infection with Neisseria gonorrhoeae and/or Chlamydia trachomatis was found more
      frequently in women with endometritis alone than in women with no endometritis or
      salpingitis (P <.001) and less frequently than in women with salpingitis (P
      =.05). Lower quadrant, adnexal, cervical motion, rebound tenderness, peritonitis,
      tenderness score, fever, and laboratory abnormalities that indicated inflammation
      and detection of gonorrheal or chlamydial infection were significantly less
      common in women with endometritis alone than in women with salpingitis but were
      somewhat more common in women with endometritis alone than among women with no
      salpingitis or endometritis. CONCLUSION: Among women with suspected pelvic
      inflammatory disease, the histopathologic manifestations of endometritis were
      associated with clinical manifestations, infection, and specific risk factors
      that were intermediate in frequency between women with salpingitis and women with
      neither endometritis nor salpingitis.

PMID- 11967493
TI  - Defective regulation of the proinflammatory immune response in women with vulvar
      vestibulitis syndrome.
AB  - OBJECTIVE: The cause of vulvar vestibulitis syndrome is unknown. To determine a
      possible role for defective immune regulation in this chronic condition,
      proinflammatory and anti-inflammatory immune responses to the 70-kd heat shock
      protein and to lipopolysaccharide were compared in women with and without vulvar
      vestibulitis syndrome. STUDY DESIGN: Whole blood cultures from 62 women with
      vulvar vestibulitis syndrome and 48 control subjects were incubated in the
      presence or absence of 5 microg/mL human recombinant 70-kd heat shock protein or
      0.1 ng/mL lipopolysaccharide for 18 hours. The culture supernatants were then
      assayed for interleukin-1 beta and interleukin-1 receptor antagonist by enzyme
      linked immunosorbent assay. RESULTS: Median levels of interleukin-1 beta were
      higher in response to heat shock protein in cultures from patients with vulvar
      vestibulitis syndrome (median, 1.07 ng/mL) as opposed to control subjects
      (median, 0.40 ng/mL; P =.006). Conversely, levels of interleukin-1 receptor
      antagonist were higher in response to heat shock protein in control subjects
      (median, 39.21 ng/mL) than in patients (median, 29.25 ng/mL; P =.009). In
      response to lipopolysaccharide, median levels of interleukin-1 beta were similar
      in patients (1.00 ng/mL) and control subjects (1.15 ng/mL); median interleukin-1
      receptor antagonist concentrations were higher in control subjects (70.0 ng/mL)
      than in patients (44.3 ng/mL; P <.0001). The ratio of interleukin-1 receptor
      antagonist to interleukin-1 beta was higher in control subjects than in women
      with vulvar vestibulitis syndrome in response to both heat shock protein (P
      =.0002) and lipopolysaccharide (P =.01). In uninduced cultures, interleukin-1
      receptor antagonist levels were also higher in control subjects (median, 1.60
      ng/mL) than in patients with vulvar vestibulitis syndrome (median, 0.62 ng/mL; P
      <.0001). CONCLUSION: A relative inability to down-regulate proinflammatory
      interleukin-1 beta activity by interleukin-1 receptor antagonist may contribute
      to the pathophysiologic features of vulvar vestibulitis syndrome.

PMID- 11967494
TI  - Use of topical recombinant human platelet-derived growth factor BB in abdominal
      wound separation.
AB  - OBJECTIVE: The purpose of this study was to determine whether the topical
      application of recombinant human platelet-derived growth factor gel influences
      healing after abdominal wound separation. STUDY DESIGN: A double-blinded
      randomized placebo-controlled trial was conducted in patients with surgical wound
      separation. RESULTS: Ten patients were randomized to treatment, and 11 patients
      were randomized to placebo. There was no difference between groups with regard to
      age, initial wound volume, type of surgical procedure, incision, or body mass
      index. Patients in the placebo group received 47 +/- 24 days of therapy. Patients
      in the treatment group received 29 +/- 14 days of therapy (P =.057). The wounds
      of the placebo group closed 54 +/- 26 days after operation. Wounds in the
      treatment group closed in 35 +/- 15 days (P =.05). Wound closure rates were
      significantly different, as determined by Kaplan-Meier analysis. CONCLUSION: Our
      preliminary study suggests that the topical application of 0.01% recombinant
      human platelet-derived growth factor gel accelerates healing of separated
      surgical wounds. Additional studies will be required to determine comparative
      efficacy and effectiveness relative to the current clinical practice of wound
      granulation and secondary closure.

PMID- 11967495
TI  - Antibodies to human papillomavirus 16 L1 virus-like particles as an independent
      prognostic marker in cervical cancer.
AB  - OBJECTIVE: Infection with high-risk human papillomavirus (HPV) types such as HPV
      16 is a major risk factor for the development of cervical cancer. HPV-16 capsid
      antibodies are detectable in approximately 50% of patients with HPV-16 DNA
      positive cervical cancer. We investigated the prognostic significance of HPV
      capsid antibodies for survival in patients with cervical cancer in comparison
      with conventional clinicopathologic features such as staging, histologic grading,
      histology, age, and treatment modality. STUDY DESIGN: Serum samples from 68
      patients with cervical cancer and 65 healthy female control subjects were
      analyzed by enzyme-linked immunosorbent assay for HPV-specific immunoglobulin G
      (IgG) antibodies to baculovirus expressed HPV-6, HPV-11, HPV-16, and HPV-18 L1
      virus-like particles (VLPs). RESULTS: HPV-16 L1 IgG antibodies were detectable in
      6 of 65 (9%) of the control subjects and in 19 of 68 (28%) of the patients with
      cervical cancer (P =.007). In the subgroup of patients with HPV-16 DNA-positive
      cervical cancer (comprising 50% of the investigated samples), HPV-16 L1
      antibodies were detected in 40%. HPV-16 L1 seropositivity was in univariate and
      multivariate analysis in addition to International Federation of Gynecology and
      Obstetrics stage, the only independent positive prognostic factor for overall
      survival (P =.01). CONCLUSION: Antibodies to HPV-16 L1 were found to be an
      independent prognostic factor for overall survival in patients with cervical
      cancer. Thus, HPV-16 infection may be involved not only in oncogenesis but also
      in tumor development and behavior.

PMID- 11967496
TI  - Pelvic organ prolapse surgery in the United States, 1997.
AB  - OBJECTIVE: Our purpose was to describe the prevalence, regional rates and
      demographic characteristics, morbidity, and mortality of pelvic organ prolapse
      surgeries in the United States. STUDY DESIGN: We used data from the 1997 National
      Hospital Discharge Survey and the 1997 National Census to calculate rates of
      pelvic organ prolapse surgeries by age, race, and regional trends. RESULTS: In
      1997, 225,964 women underwent surgery for prolapse (22.7 per 10,000 women). The
      mean age of these women was 54.6 years (+/-15.2). The South had the highest rate
      of surgery (29.3 per 10,000) and the Northeast had the lowest (16.1 per 10,000).
      The surgery rate for whites (19.6 per 10,000) was 3 times greater than that for
      African Americans (6.4 per 10,000). Although 16% of surgeries had complications,
      mortality was rare (0.03%). CONCLUSION: Pelvic organ prolapse surgery is common.
      Regional and racial differences in rates of surgery may reflect physician
      practice, patient preferences, and gynecologic care utilization.

PMID- 11967498
TI  - Laparoscopic versus open Burch retropubic urethropexy: comparison of morbidity
      and costs when performed with concurrent vaginal prolapse repairs.
AB  - OBJECTIVE: The purpose of this study was to determine the morbidity and cost that
      are associated with laparoscopic and open Burch retropubic urethropexy when they
      are performed with concurrent vaginal prolapse repairs. STUDY DESIGN: We
      conducted a retrospective study of all patients who had undergone laparoscopic (n
      = 76) or open (n = 143) Burch retropubic urethropexy with at least 1 concurrent
      vaginal repair for symptomatic prolapse. We compared demographic data, level of
      prolapse, operative and postoperative details, medical and surgical histories,
      complications, and hospital charges. RESULTS: The group with open retropubic
      urethropexy had an older age, greater degree of prolapse, fewer concurrent
      hysterectomies, and a greater number of vaginal procedures than the group with
      laparoscopic retropubic urethropexy. There were minimal differences in
      complications and no differences in the estimated blood loss, operative time,
      hemoglobin change, hospitalization, or hospital charges between the 2 groups.
      CONCLUSION: Traditional benefits of laparoscopic retropubic urethropexy were not
      apparent when vaginal prolapse repairs were performed.

PMID- 11967497
TI  - Effects of tibolone and continuous combined hormone replacement therapy on
      mammographic breast density.
AB  - OBJECTIVE: Our purpose was to compare the effects of tibolone, continuous
      combined hormone replacement therapy, and placebo on mammographic breast density.
      STUDY DESIGN: A prospective, randomized, double-blind placebo-controlled study
      was performed. A total of 166 postmenopausal women were equally randomized to
      receive tibolone 2.5 mg, estradiol 2 mg/norethisterone acetate 1 mg (E(2)/NETA),
      or placebo. Mammograms were performed at baseline and after 6 months of
      treatment. Mammographic density was quantified according to the Wolfe
      classification and by the percentage area of the breast that had a dense pattern.
      RESULTS: An increase in mammographic density was much more common among women
      receiving continuous combined hormone replacement therapy (46%-50%) than among
      those receiving tibolone (2%-6%) and placebo (0%) treatment. The difference
      between E(2)/NETA and placebo was highly significant (P <.001). Treatment with
      tibolone did not differ from that with placebo. The relative risk of an increase
      in breast density for E(2)/NETA versus tibolone was found to be 8.3 (95% CI 2.7
      25.0). CONCLUSION: An increase in mammographic density should be regarded as an
      unwanted side effect of hormone replacement therapy. In contrast to
      estrogen/progestogen treatment, tibolone seems to exert little stimulation of
      breast tissue.

PMID- 11967499
TI  - Neither long-term treatment with raloxifene nor hormone replacement therapy
      modulate cardiac function in healthy postmenopausal women: two randomized,
      placebo-controlled, 2-year studies.
AB  - OBJECTIVE: Our purpose was to investigate the long-term effects of raloxifene,
      compared with opposed and unopposed estrogen replacement therapy, on
      echocardiographic parameters of left ventricular systolic function in healthy
      postmenopausal women. A total of 157 women were studied in 2 randomized, double
      blind, placebo-controlled, 2-year studies. STUDY DESIGN: In study I, 60
      postmenopausal women who had undergone hysterectomy received daily raloxifene, 60
      mg (n = 15); raloxifene, 150 mg (n = 15); conjugated equine estrogens (CEE),
      0.625 mg (n = 15); or placebo (n = 15). In study II, 97 postmenopausal women who
      had not undergone hysterectomy received daily raloxifene, 60 mg (n = 24);
      raloxifene, 150 mg (n = 24); CEE, 0.625 mg, plus medroxyprogesterone acetate
      (MPA), 2.5 mg (n = 24); or placebo (n = 25). M-mode, quantitative 2-dimensional
      and Doppler echocardiographic measurements were performed at baseline and after 1
      and 2 years. RESULTS: Neither after 1 year nor after 2 years of treatment were
      echocardiographic parameters found to differ from baseline in both raloxifene
      groups, as well as in the unopposed CEE and the CEE/MPA groups, compared with the
      placebo group. CONCLUSION: Within 2 years of raloxifene treatment, no effect on
      echocardiographic parameters of left ventricular systolic function was found.
      Unopposed CEE or CEE/MPA also showed no effect.

PMID- 11967500
TI  - Factors that predict low hematocrit levels in the postpartum patient after
      vaginal delivery.
AB  - OBJECTIVE: The purpose of this study was to provide a viable alternative to
      routine postpartum hematocrit measurement, by a determination of the clinical
      risk factors that identify patients with anemia and an examination of the
      resulting cost savings. STUDY DESIGN: In this retrospective review, cases
      (postpartum hematocrit level, <26%; subgroup hematocrit level, <23%) and control
      subjects were culled from the records of all vaginal deliveries from February
      1997 to July 1998. Charts were reviewed for demographic characteristics, medical
      history, nursing assessments, and postpartum hematocrit measurements. Logistic
      regression modeling determined the best set of risk factors for the
      identification of low postpartum hematocrit levels. RESULTS: From 1484 vaginal
      deliveries, 117 of the women (8%) had postpartum hematocrit levels of <26%.
      Estimated blood loss of >500 mL, Hispanic ethnicity, dizziness, or third- or
      fourth-degree laceration were the factors that identified 82.9% of the women with
      hematocrit levels of <26% and identified 97.4% of the women with hematocrit
      levels of <23%. Only 39.3% of the women would have required postpartum hematocrit
      measurement to obtain these detection rates. CONCLUSION: Four risk factors
      (estimated blood loss of >500 mL, Hispanic ethnicity, dizziness, and third- or
      fourth-degree laceration) can safely determine the necessity of a postpartum
      hematocrit measurement.

PMID- 11967501
TI  - Nitric oxide induced cervical ripening in the human: Involvement of cyclic
      guanosine monophosphate, prostaglandin F(2 alpha), and prostaglandin E(2).
AB  - OBJECTIVE: The purpose of the study was to investigate possible mechanisms and
      morphologic changes involved in nitric oxide-induced cervical ripening. STUDY
      DESIGN: Women scheduled for surgical termination of first trimester pregnancy
      were randomized to 1 of 3 groups: isosorbide 5-mononitrate 40 mg 4 hours or 10
      hours before the operation or no preoperative treatment. Cervical specimens were
      obtained for the analysis of tissue levels of cyclic guanosine monophosphate,
      cyclic adenosine monophosphate, cyclo-oxygenase 1, cyclo-oxygenase 2,
      prostaglandin F(2 alpha), and prostaglandin E(2) or were fixed in glutaraldehyde
      for microscopy. RESULTS: Increased levels of cyclic guanosine monophosphate,
      cyclo-oxygenase 2, prostaglandin F(2 alpha), and prostaglandin E(2) were found in
      samples that were exposed to isosorbide 5-mononitrate compared with control
      samples. Electron microscopy revealed stromal edema and collagen disorganization
      after isosorbide 5-mononitrate treatment. CONCLUSION: Cyclic guanosine
      monophosphate, prostaglandin F(2 alpha), and prostaglandin E(2) are involved in
      nitric oxide-induced cervical ripening. Nitric oxide causes morphologic changes
      similar to those changes seen during spontaneous cervical ripening.

PMID- 11967503
TI  - Substrate utilization and hormonal responses to moderate intensity exercise
      during pregnancy and after delivery.
AB  - OBJECTIVE: This study was undertaken to examine substrate utilization and
      hormonal responses to moderate intensity exercise in the same group of women
      across gestation. STUDY DESIGN: Glucose, triglyceride, insulin, glucagon,
      cortisol, growth hormone, and blood urea nitrogen levels were measured in 12
      women at rest and after exercise. Heart rate, oxygen uptake, and respiratory
      exchange ratio were measured at rest and during exercise. Urine urea nitrogen
      levels, urine volume, and creatinine levels were measured 24 hours before and
      after exercise. Each woman completed a 30-minute treadmill walk at 65% of her
      predicted maximal heart rate at the same time of day during the 22nd and 33rd
      weeks of gestation and at 14 weeks after delivery. RESULTS: There were no
      significant differences between exercise trials in oxygen uptake, respiratory
      exchange ratio, or heart rate. Pregnancy elevated resting triglyceride levels but
      lowered plasma glucose levels. Exercise during pregnancy caused a reduction in
      plasma glucose levels but elevated circulating triglyceride levels (P <.05).
      Resting levels of cortisol, growth hormone, and insulin were elevated during
      pregnancy compared with after delivery, but resting glucagon levels were not
      affected by pregnancy. Exercise caused circulating levels of cortisol, growth
      hormone, and glucagon to increase (P <.05). The exercise-induced change in the
      cortisol level was greater during pregnancy than that after delivery. The
      exercise-induced changes in growth hormone and glucagon levels were greatest
      after delivery compared with those during pregnancy (P <.05). Exercise reduced
      insulin levels (P <.05), with the greatest reduction at 33 weeks' gestation.
      There were no significant differences in urine urea nitrogen excretion as a
      result of exercise. CONCLUSIONS: Certain substrate and hormonal responses to
      exercise are altered as pregnancy progresses. Quantitatively, protein appears to
      be a relatively unimportant fuel during a 30-minute bout of moderate intensity
      exercise in this group of women evaluated during pregnancy and after delivery.
      Furthermore, a 30-minute bout of moderate intensity exercise would not be
      expected to compromise fetal amino acid availability.

PMID- 11967502
TI  - Clinical predictors for a high risk for the development of diabetes mellitus in
      the early puerperium in women with recent gestational diabetes mellitus.
AB  - OBJECTIVE: The purpose of this study was to identify which maternal, antepartum,
      or neonatal clinical parameters were predictive for a high risk of diabetes
      mellitus in the puerperium in women with recent gestational diabetes mellitus and
      to calculate the associated diabetes mellitus rates and odds ratios. STUDY
      DESIGN: One thousand six hundred thirty-six women underwent an oral glucose
      tolerance test within 1 to 4 months of delivery. Demographic, historic, and
      antenatal glycemic parameters and neonatal outcome parameters were tested by
      univariate and multivariate logistic regression for risk of postpartum diabetes
      mellitus. Continuous variables were divided into quartiles that compared the
      upper to lower quartile adjusted odds ratio and prevalence of diabetes mellitus.
      RESULTS: Postpartum diabetes mellitus was diagnosed in 230 women (14.1%)
      according to the American Diabetes Association criteria (1997). No maternal
      demographic or neonatal parameters were significantly associated with diabetes
      mellitus. The final model of independent predictors in decreasing significance
      included the highest fasting plasma glucose level during pregnancy, any fasting
      plasma glucose level of > or = 105 mg/dL (class A(2)), the area under the curve
      of pregnancy oral glucose tolerance test, gestational age at diagnosis, previous
      gestational diabetes mellitus history, and 50-g glucose challenge test results.
      The fasting plasma glucose level was the best discriminator, with a 21-fold (95%
      CI, 4.6-96.3) increased odds ratio comparing the 4th quartile (fasting plasma
      glucose level, >121 mg/dL; diabetes mellitus rate, 36.7%) to 1st quartile
      (fasting plasma glucose level, < 95 mg/dL; diabetes mellitus rate, 0.5%). The
      presence of previous gestational diabetes mellitus or current class A(2)
      gestational diabetes mellitus approximately doubled the odds ratio for diabetes
      mellitus. The odds ratio increased 3- to 4-fold when the area under the curve was
      > or = 33.36 min small middle dot g/dL (4th quartile) or the glucose challenge
      test was > or = 155 mg/dL (2nd-4th quartiles) and decreased > 50% if gestational
      diabetes mellitus was diagnosed at > 27 weeks (3rd-4th quartile). CONCLUSION:
      During pregnancy, the highest fasting glucose level, followed by the severity of
      glucose intolerance, and earlier gestational diabetes mellitus diagnosis were the
      best predictors for postpartum diabetes mellitus. Diabetic education should begin
      during pregnancy, especially for women who are identified to be at a high risk
      when they are highly motivated and under medical care.

PMID- 11967504
TI  - Outcomes of dichorionic triplet pregnancies.
AB  - OBJECTIVE: The objective of this study was to describe outcomes in a series of
      dichorionic triplet pregnancies. STUDY DESIGN: All triplet pregnancies evaluated
      in our obstetric sonography unit from 1993 to 2000 were identified. Those
      containing a monochorionic twin pair were included. Prenatal and neonatal records
      were reviewed. Statistical comparison was performed by using Wilcoxon matched
      pairs signed-ranked sum test. RESULTS: Seventeen cases met inclusion criteria.
      Two pregnancies (11.8%) were delivered spontaneously before viability, at 22 and
      21 weeks. Twin-twin transfusion syndrome was diagnosed in the second trimester in
      the monochorionic pair in 3 pregnancies (17.6%). In the remaining 12 pregnancies,
      mean gestational age at delivery was 33.5 +/- 2.3 weeks. The median birth weight
      of 23 neonates from individual monochorionic twin pairs was 1810 g (interquartile
      range, 1540-2180 g), which was significantly lower than the median birth weight
      of 12 triplets supplied by a separate placenta, 2125 g (interquartile range, 1762
      2390 g) (P =.01). CONCLUSION: Twin-twin transfusion syndrome or spontaneous loss
      before viability complicated approximately 30% of dichorionic triplet
      pregnancies. Lower birth weights were noted in triplets from monochorionic twin
      pairs.

PMID- 11967505
TI  - Physician attitudes concerning legal coercion of pregnant alcohol and drug
      abusers.
AB  - OBJECTIVE: We sought to determine the attitudes of obstetricians, pediatricians,
      and family practice physicians in Michigan concerning involvement of the criminal
      justice system in preventing drug and alcohol abuse during pregnancy. STUDY
      DESIGN: Physicians were sent a questionnaire by mail asking for their agreement
      with statements concerning the involvement of the criminal justice system with
      respect to substance abuse during pregnancy. RESULTS: Nearly all (95%) agreed
      that pregnant women have a moral duty to ensure they had healthy babies; 59%
      agreed that they should also have a legal responsibility to do so. Most
      physicians (77%) agreed that screening for acquired immunodeficiency syndrome
      during pregnancy should be mandatory. Almost as high a percentage (61% to 75%
      depending on subspecialty) were also in favor of mandatory screening for alcohol
      abuse; agreement for screening for illicit drugs was much lower (43% to 55%
      depending on subspecialty). Despite their consensus (61%) that fear of
      prosecution would deter pregnant abusers from seeking prenatal care, most were in
      agreement that existing laws regarding child abuse and neglect need to be
      redefined to include alcohol (54%) and drug abuse (61%) during pregnancy; 52%
      were in favor of enacting a statute that includes drug or alcohol use during
      pregnancy as "child abuse" for purposes of removing that child from maternal
      custody. Physicians were highly in favor of compulsory treatment for illicit drug
      use and alcohol abuse for women already in the criminal justice system (82%-83%),
      neutral with respect to court-ordered contraception for alcohol- (50%) and drug
      abusing women (47%), and opposed to criminal prosecution for either alcohol abuse
      (18%-31% depending on subspecialty) or illicit drug use (23%-34%) during
      pregnancy. CONCLUSIONS: Other than criminal prosecution, physicians are not
      opposed to involvement of the legal justice system in preventing alcohol and drug
      abuse during pregnancy.

PMID- 11967506
TI  - Short-term maternal outcomes that are associated with the EXIT procedure, as
      compared with cesarean delivery.
AB  - OBJECTIVE: The ex utero intrapartum treatment procedure was developed to treat
      iatrogenic tracheal obstruction that resulted from in utero fetal therapy for
      congenital diaphragmatic hernia. The ex utero intrapartum treatment procedure
      allows for controlled intubation while the neonate is maintained on placental
      circulation, prolonging operative time. This study evaluates whether there is
      increased maternal morbidity associated with this procedure compared with routine
      cesarean deliveries. STUDY DESIGN: Maternal outcomes on 34 patients who underwent
      the ex utero intrapartum treatment procedure were evaluated. Infection rate,
      estimated blood loss, need for transfusion, and length of postoperative hospital
      stay were compared to maternal outcomes from 52 non-laboring patients who
      underwent non-emergent primary cesarean delivery of singleton fetuses during the
      same time interval. RESULTS: The rate of chorioamnionitis was similar between
      groups (26% vs 21%; P =.57). Postpartum wound complications were more common in
      patients who underwent ex utero intrapartum treatment (15% vs 2%; P =.03),
      although the rate of endometritis was similar (15% vs 10%; P =.50). Estimated
      blood loss was higher in the patients who underwent ex utero intrapartum
      treatment (1104 mL vs 883 mL; P <.001), but there was no difference between
      groups in hematocrit level change or postpartum hospital stay. CONCLUSION: Women
      who undergo the ex utero intrapartum treatment procedure experience more wound
      complications but no difference in postoperative hematocrit level change or
      postpartum length of stay.

PMID- 11967507
TI  - Polyamine effects on human myometrial contractility.
AB  - OBJECTIVE: This study was undertaken to investigate the effects of the polyamine
      spermine on human uterine contractility. STUDY DESIGN: Under physiologic
      conditions, an isometric tension recording was performed in isolated myometrial
      strips from biopsy specimens obtained at elective cesarean delivery (n = 24
      specimens) and from premenopausal hysterectomy specimens (n = 6 specimens). The
      effects of spermine (1 micromol/L-10 mmol/L in cumulative doses) on spontaneous,
      agonist-induced myometrial contractions were measured, and dose response curves
      were constructed. The pD(2) (-log EC(50)) values and the maximal inhibition
      values achieved were compared for spontaneous and agonist-induced contractions.
      RESULTS: Spermine exerted a potent relaxant effect on all spontaneous and agonist
      induced myometrial contractions, with mean maximal inhibition values between
      62.8% +/- 4.3% and 91.4% +/- 1.8% and pD(2) values between 2.66 +/- 0.23 and 4.01
      +/- 0.20. Its inhibitory effect varied significantly with different contraction
      types (pD(2), P <.05; mean maximal inhibition, P <.001), and it was least potent
      on BAY K 8644-elicited contractions (pD(2), P <.05; mean maximal inhibition, P
      <.01). CONCLUSION: The polyamine spermine exerts a potent relaxant effect on
      human uterine tissue. This effect appears to be mediated, at least partially, by
      calcium antagonism. Polyamines may play a role in the maintenance of uterine
      quiescence during pregnancy.

PMID- 11967508
TI  - Differences in postpartum morbidity in women who are infected with the human
      immunodeficiency virus after elective cesarean delivery, emergency cesarean
      delivery, or vaginal delivery.
AB  - OBJECTIVE: The aim of this study was to assess the impact of elective cesarean
      delivery on postpartum morbidity in women who are infected with the human
      immunodeficiency virus (HIV). STUDY DESIGN: We performed a retrospective study of
      401 women who were infected with HIV who were delivered in a single reference
      center from 1989 through 1999. Women who had cesarean deliveries (n = 201), of
      which 109 were elective and 92 were emergency, were compared with a group of
      women who were delivered vaginally (n = 200), composed of the women who were
      infected with HIV preceding each cesarean delivery. RESULTS: One or more serious
      complications occurred after 12% of emergency cesarean deliveries, after 6.4% of
      elective cesarean deliveries, and after 4% of vaginal deliveries (P =.04). In a
      multivariate analysis, which was adjusted for maternal CD4 lymphocyte count and
      antepartum hemorrhage, the relative risk of any postpartum complication (serious
      or minor) was increased by 1.85 (range, 1.00-3.39) after elective cesarean
      delivery and 4.17 (range, 2.32-7.49) after emergency cesarean delivery, compared
      with vaginal deliveries (P =.0001). CONCLUSION: Postpartum morbidity in women who
      are infected with HIV was highest after emergency, rather than elective, cesarean
      deliveries.

PMID- 11967509
TI  - Severe preeclampsia at <25 weeks of gestation: maternal and neonatal outcomes.
AB  - OBJECTIVE: The purpose of this study was to determine maternal and neonatal
      outcomes of women who were delivered because of severe preeclampsia before 25
      weeks of gestation. STUDY DESIGN: We used a computerized database to identify
      3800 women with preeclampsia among 35,937 deliveries from 1991 to 1997. Of these,
      39 women (1%) with severe preeclampsia were delivered before 25 weeks of
      gestation. We abstracted outcomes in these women and their newborns. RESULTS: All
      39 women had severe preeclampsia as defined by clinical and/or laboratory
      criteria. Thirty-three of the 39 women had severe-range hypertension. Twenty-one
      women (54%) experienced morbidity that included abruptio placentae (n = 5), HELLP
      (hemolysis, elevated liver enzymes, and low platelet count) syndrome (n = 9),
      renal insufficiency (n = 5), and eclampsia (n = 3). No women required dialysis or
      intensive care unit admission, and none of the women died. All maternal
      morbidities reversed after delivery. Twenty-two infants (55%) were live-born.
      Only 4 infants (10%) survived, all with severe handicaps. CONCLUSION: In women
      with severe preeclampsia before 25 weeks of gestation, delivery is associated
      with minimal short-term maternal morbidities, although neonatal morbidity and
      death are appreciable.

PMID- 11967510
TI  - Risk factors for early death among extremely low-birth-weight infants.
AB  - OBJECTIVE: The purposes of this study were to compare the clinical
      characteristics of extremely low birth-weight infants (501-1000 g birth weight)
      who die early (<12 hours of age) with those of infants who die >12 hours after
      birth and infants who survive to neonatal intensive care unit discharge and to
      develop a model of risk for early death. STUDY DESIGN: Perinatal data were
      prospectively collected on 5986 infants in the 12 participating centers of the
      National Institute of Child Health and Human Development Neonatal Research
      Network from March 1993 through December 1997. Maternal and neonatal
      characteristics of infants who died early were compared with infants who survived
      and infants who died beyond 12 hours of age. A model for risk for early death was
      developed by logistic regression analysis, with results expressed as odds ratio
      with 95% CI. RESULTS: Mothers of infants who died early were more likely to be
      delivered in an inborn setting and experience labor and were less likely to have
      hypertension or preeclampsia, to receive antenatal corticosteroids, or to be
      delivered by cesarean birth than mothers of infants who died >12 hours after
      birth or infants who survived. Infants who died early were more likely to have
      lower Apgar scores and lower gestational age/birth weight and were less likely to
      be intubated at birth and to receive mechanical ventilation and surfactant
      therapy than infants who died >12 hours after birth or infants who survived.
      Greater risk for early death versus survival to neonatal intensive care unit
      discharge was associated with the lack of surfactant administration (odds ratio,
      8.6; 95% CI, 6.3-11.9), lack of delivery room intubation (odds ratio, 5.3; 95%
      CI, 3.5-8.1), lack of antenatal corticosteroid use (odds ratio, 2.3; 95% CI, 1.6
      3.2), lower 1-minute Apgar score (odds ratio, 2.0; 95% CI, 1.8-2.2), male sex
      (odds ratio, 1.7; 95% CI, 1.3-2.3), multiple gestation (odds ratio, 1.7; 95% CI,
      1.2-2.5), no tocolytics (odds ratio, 1.7; 95% CI, 1.2-2.3), lower gestational age
      per week (odds ratio, 1.4; 95% CI, 1.3-1.6), and lower birth weight per 50 g (95%
      CI, 1.2-1.4). CONCLUSION: Early death (<12 hours of age) among extremely low
      birth-weight infants may reflect an assessment of non-viability by obstetricians
      and neonatologists.

PMID- 11967511
TI  - The comprehensive midtrimester test: high-sensitivity Down syndrome test.
AB  - OBJECTIVE: The purpose of this study was to develop a highly sensitive algorithm
      for midtrimester Down syndrome detection. STUDY DESIGN: Urine (hyperglycosylated
      human chorionic gonadotropin, beta-core fragment of human chorionic
      gonadotropin), serum (alpha-fetoprotein, human chorionic gonadotropin and
      unconjugated estriol [uE(3)]), and ultrasound biometry (nuchal thickness, humerus
      length, the presence of gross ultrasonographic anomalies), and maternal age were
      measured at genetic amniocentesis. Stepwise logistic regression analysis was used
      to identify the most significant markers. A multivariate Gaussian algorithm plus
      age was used to derive patient-specific Down syndrome risk. Sensitivity and false
      positive rates at different risk thresholds and the area under the receiver
      operating characteristic curve were determined. A probability value of <.05 was
      significant. RESULTS: There were 568 study cases with 17 Down syndrome cases
      (3.0%). The mean (+/-SD) maternal and gestational ages for the study group were
      36.9 (+/-3.5) years and 16.2 (+/-1.4) weeks, respectively. The significant
      markers were nuchal thickness (P =.0001), hyperglycosylated human chorionic
      gonadotropin(P <.001), and beta-core fragment (P <.002). Neither maternal age nor
      gross sonographic anomaly contributed significantly to Down syndrome detection.
      The comprehensive midtrimester test was extremely efficient for Down syndrome
      detection in advanced maternal age only cases with a sensitivity of 92.3% at a
      0.8% false-positive rate. In women <35 years old, all the Down syndrome cases
      were detected at 2.2% false positive rate. For the overall population, the
      sensitivity was 93.7% at 5% false-positive rate. CONCLUSION: In a preliminary
      study, the comprehensive midtrimester test appeared highly sensitive in different
      age groups. Gross anomaly detection was not required for high performance, which
      makes the comprehensive midtrimester test potentially suitable for low-risk
      screening and as an alternative to amniocentesis in women who wish to avoid the
      procedure. This was a small study; thus, the clinical value of this test can only
      be established in large trials.

PMID- 11967512
TI  - Clinical implications of velamentous cord insertion in triplet gestations.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence of
      velamentous cord insertion and to evaluate the association between velamentous
      cord insertion and small-for-gestational age infants in triplet gestations. STUDY
      DESIGN: We reviewed our computerized database to identify all cases of
      velamentous cord insertion in triplet gestations who were delivered at our
      institution from January 1995 through December 1999. Triplet gestations without
      velamentous cord insertion who were delivered during this period were used as
      control subjects. Birth weights and pregnancy outcomes were obtained from medical
      records. Data were analyzed with descriptive statistics, analysis of variance,
      and chi(2) with Fisher exact test, where appropriate. RESULTS: Thirty-nine sets
      of triplets (117 infants) were delivered during the study period. Of these, 11
      sets of triplets (28.2%) had a velamentous insertion of at least one umbilical
      cord. Infants with velamentous cord insertion were more likely to be small-for
      gestational age than infants without velamentous cord insertion (33% vs 8%, P
      =.02). There were no significant differences in the rates of pregnancy
      complications between the two groups. CONCLUSION: Velamentous cord insertion is
      found frequently in triplet gestations and is significantly associated with small
      for-gestational age in triplet neonates.

PMID- 11967513
TI  - Effects of maternal betamethasone administration on fetal and maternal blood
      pressure and heart rate in the baboon at 0.7 of gestation.
AB  - OBJECTIVE: We sought to determine the effects of the intramuscular maternal
      administration of betamethasone to the pregnant baboon at 0.7 of gestation on
      fetal blood pressure and heart rate. STUDY DESIGN: We treated pregnant baboons at
      0.7 of gestation with intramuscular betamethasone (n = 4), at a weight-adjusted
      dose equivalent to the daily dose administered to women in preterm labor or with
      saline solution (n = 5). Four injections were given at 12-hour intervals. Fetal
      and maternal blood pressure and heart rate were recorded continuously. Within
      group differences and between-group differences were analyzed with repeated
      measures analysis of variance. RESULTS: Fetal blood pressure increased
      significantly after betamethasone treatment. Fetal heart rate, maternal blood
      pressure, and heart rate did not change. CONCLUSION: Exposure of the developing
      primate fetus to exogenous glucocorticoid at 0.7 of gestation elevates fetal
      blood pressure. These findings confirm and extend the observations in the fetal
      sheep. Further studies are needed to evaluate the mechanisms that are involved
      and possible long-term consequences of these cardiovascular effects of antenatal
      glucocorticoid exposure in the fetal primate.

PMID- 11967514
TI  - Long-term cognitive benefits of antenatal corticosteroids for prematurely born
      children with cranial ultrasound abnormalities.
AB  - OBJECTIVE: Previous studies have examined possible long-term effects of antenatal
      corticosteroids, but not by the presence of neonatal brain lesions. This study of
      long-term neurodevelopmental outcomes of antenatal corticosteroid exposure among
      preterm, very-low-birth-weight infants investigated whether the effects are
      differential by the presence of neonatal brain injury. STUDY DESIGN: Prospective
      cohort study of cognition, behavior, and cerebral palsy in 251 children (ages 6-8
      years) born at < or = 32 weeks of gestation. This sample included 91 children
      with abnormal neonatal cranial ultrasound findings and 106 children who had been
      exposed to antenatal corticosteroids. RESULTS: In children with abnormal cranial
      ultrasound findings, a complete course of antenatal corticosteroids was
      associated with an 8.7-point advantage in IQ (95% CI, 1.8, 15.6; P = .016),
      controlling for confounding factors. Both verbal and nonverbal cognitive scores
      were increased in a dose-response manner. The advantage was greater for infants
      born at < or = 28 weeks of gestation and in those with ventriculomegaly. In
      children with normal cranial ultrasound scans, cognitive function was not related
      to antenatal corticosteroid exposure. No statistically significant associations
      were observed between antenatal corticosteroid exposure and either childhood
      behavioral scores or cerebral palsy. CONCLUSION: Antenatal corticosteroids appear
      to confer substantial long-term benefits on cognition of very-low-birth-weight
      infants with cranial ultrasound abnormalities.

PMID- 11967515
TI  - Serial aggressive platelet transfusion for fetal alloimmune thrombocytopenia:
      platelet dynamics and perinatal outcome.
AB  - OBJECTIVES: Our purpose was to describe the fetal loss rate and platelet dynamics
      in fetal alloimmune thrombocytopenia managed by serial platelet transfusions.
      METHODS: Retrospective analysis over 10 years of consecutive pregnancies affected
      by fetal alloimmune thrombocytopenia requiring in utero platelet transfusions.
      RESULTS: There were 2 perinatal losses in 12 pregnancies managed by 84 platelet
      transfusions. One was obviously procedure related from exsanguination despite
      platelet transfusion. The attributable procedure related fetal loss rate was 1.2%
      per procedure but 8.3% per pregnancy. The median rate of fall in fetal platelet
      count per day after transfusion was lower at the placental cord insertion (n =
      54) 40.5 x 10(9)/L (range, 5.4-96.1 x 10(9)/L) compared with that at the
      intrahepatic vein (n = 30) 50.9 x 10(9)/L,(range, 29.5-91 x 10(9)/L) (P = .0009).
      CONCLUSION: Pooling our results with those previously published yields a
      cumulative risk of serial weekly transfusions of approximately 6% per pregnancy,
      indicating the need for development of less invasive approaches.

PMID- 11967516
TI  - Effects of the selective estrogen receptor modulator, raloxifene, on carotid
      artery pulsatility index in postmenopausal women.
AB  - OBJECTIVE: Estrogen replacement therapy after menopause reduces the incidence of
      arterial disease and cerebrovascular events. The reduced incidence also seems to
      be due to a positive effect of estrogens on brain blood flow as shown by a
      decrease in the carotid artery pulsatility index. Raloxifene, a second-generation
      selective estrogen receptor modulator, has aroused considerable interest because
      of its tissue-specific agonist-antagonist effect on estrogen receptors. However,
      there have been no studies on the effect of raloxifene on carotid blood flow
      after menopause. METHODS: A total of 66 healthy women in postmenopause for more
      than a year were divided randomly into 2 groups: the first group (n = 33; mean
      age +/- SD, 53.3 +/- 5.2 years) was treated with raloxifene (one 60-mg capsule
      per day) for 6 months, and the other group (n = 33; mean age +/- SD, 51.9 +/- 4
      years) was untreated. Doppler ultrasonography was used to measure carotid artery
      pulsatility index (PI) at the beginning of the study and at 2-month intervals.
      RESULTS: A reduction in carotid artery PI was observed in all patients receiving
      raloxifene. No significant changes were observed in the control group. The
      reduction with respect to baseline values was 6.1%(P <.05) after 2 months, 11.2%
      (P <.05) after 4 months, and 13.2% (P <.05) after 6 months of therapy. The higher
      the baseline PI, the greater was its reduction after therapy. CONCLUSIONS: After
      6 months of therapy, raloxifene induced a reduction in PI similar to that
      reported after estrogen therapy. The present results further our understanding of
      the mechanisms by which raloxifene might reduce the incidence of cardiovascular
      disease in postmenopausal women.

PMID- 11967517
TI  - Effects of a laboratory-based skills curriculum on laparoscopic proficiency: a
      randomized trial.
AB  - OBJECTIVE: The purpose of this study was to determine the effect and validity of
      an intensive laboratory-based laparoscopic skills training curriculum on
      operative proficiency in obstetrics and gynecology residents. STUDY DESIGN: This
      was a prospective, randomized, block-design trial of postgraduate year 3 and 4
      residents. The following study schedule was used: week 1 (pre-randomization)
      included an orientation to study objectives, the administration of a laparoscopic
      experience questionnaire, timed video-laparoscopic drills (5 total), and the
      performance of a video-recorded laparoscopic partial salpingectomy; during weeks
      2 and 3, the skills group residents repeated the laparoscopic drills 30 minutes
      daily for 10 days, and the control group residents had no formal practice
      sessions; during week 4, the week 1 evaluation was repeated. Operative
      proficiency was quantified by the Global Skills Assessment Tool through blinded,
      independent scoring of videotapes. RESULTS: Twenty-six residents (skills group,
      12; control group, 14) consented to the trial. Patient-related issues excluded 8
      residents (30%). At week 1, no significant differences existed in previous
      laparoscopic experience, timed video skills, or resident operative proficiency
      (Global Skills Assessment Tool score) between cohorts. At week 4, both groups
      significantly improved their timed drill test scores. The percent reduction in
      time from baseline was of greater magnitude in the skills group versus control
      group (51% vs 18%,P <.0001). Laparoscopic performance also improved in both
      cohorts (P =.002). However, only the skills group demonstrated significant intra
      cohort improvement from baseline (mean, 4.9 points; P =.015; 95% CI, 1-7.5).
      CONCLUSION: A core curriculum of intensive video laparoscopic skills training
      improves not only technical but also operative performance among postgraduate
      year 3 and 4 residents.

PMID- 11967518
TI  - Repeated doses of antenatal corticosteroids in animals: a systematic review.
AB  - OBJECTIVE: The purpose of this review was to assess the effects of repeated doses
      of antenatal corticosteroids on lung and brain function and on growth restriction
      in animals. STUDY DESIGN: MEDLINE and EMBASE were searched for randomized
      controlled trials that compared repeated doses of antenatal corticosteroids
      versus a single dose, with or without placebo, in pregnant animals. RESULTS:
      Nineteen studies were included. The animals that were studied included sheep,
      monkeys, rabbits, and mice. There were 8 studies that assessed the effects of
      repeated doses of antenatal corticosteroids on lung function. All the studies
      reported improvement in lung function after repeated doses of antenatal
      corticosteroids. Seven studies investigated the effects of repeated doses of
      antenatal corticosteroids on brain or nervous system function or growth; all the
      studies found adverse effects with repeated doses of antenatal corticosteroids.
      Eleven studies looked at the effect of repeated doses of antenatal
      corticosteroids on fetal growth. Nine studies found evidence of fetal growth
      restriction with repeated doses of antenatal corticosteroids. One study assessed
      long-term behavioral outcomes in mice and found no effect. CONCLUSION: Evidence
      from randomized controlled trials in animals suggests that repeated doses of
      antenatal corticosteroids may have beneficial effects in terms of lung function
      but may have adverse effects on brain function and fetal growth. Because of the
      differences between animals and humans, it is difficult to extrapolate directly
      the results of these studies to humans. Therefore, randomized controlled trials
      in humans are needed to assess the effects of repeated courses of antenatal
      corticosteroids for pregnant women who are at increased risk of preterm birth in
      terms of important perinatal, neonatal, and maternal outcomes.

PMID- 11967519
TI  - The G-spot is the female prostate.

PMID- 11967520
TI  - A VBAC question.

PMID- 11967521
TI  - Obstetrician-gynecologists performing genetic amniocentesis may be misleading
      themselves and their patients.

PMID- 11967522
TI  - Low maternal plasma volume may be the answer!

PMID- 11967523
TI  - Surgical repair of cystocele with mesh by the vaginal route.

PMID- 11967524
TI  - Factor V Leiden mutation and preeclampsia.

PMID- 11967525
TI  - Obstructive mullerian anomalies.

PMID- 11967526
TI  - Extensive and divergent circadian gene expression in liver and heart.
AB  - Many mammalian peripheral tissues have circadian clocks; endogenous oscillators
      that generate transcriptional rhythms thought to be important for the daily
      timing of physiological processes. The extent of circadian gene regulation in
      peripheral tissues is unclear, and to what degree circadian regulation in
      different tissues involves common or specialized pathways is unknown. Here we
      report a comparative analysis of circadian gene expression in vivo in mouse liver
      and heart using oligonucleotide arrays representing 12,488 genes. We find that
      peripheral circadian gene regulation is extensive (> or = 8-10% of the genes
      expressed in each tissue), that the distributions of circadian phases in the two
      tissues are markedly different, and that very few genes show circadian regulation
      in both tissues. This specificity of circadian regulation cannot be accounted for
      by tissue-specific gene expression. Despite this divergence, the clock-regulated
      genes in liver and heart participate in overlapping, extremely diverse processes.
      A core set of 37 genes with similar circadian regulation in both tissues includes
      candidates for new clock genes and output genes, and it contains genes responsive
      to circulating factors with circadian or diurnal rhythms.

PMID- 11967531
TI  - Evidence of en bloc duplication in vertebrate genomes.
AB  - It has been 30 years since it was first proposed that the vertebrate genome
      evolved through several rounds of genome-wide duplications (polyploidizations).
      Despite rapid advances in genetics, including sequencing of the complete genomes
      of several divergent species, this hypothesis has not been tested rigorously and
      is still a matter of debate. If polyploidizations occurred during chordate
      evolution, there should be a network of paralogous regions in the present-day
      jawed vertebrate (Gnathostomata) genomes. Here we present an investigation of the
      major histocompatibility complex (MHC) paralogous regions, which we accomplished
      by characterizing the corresponding region in amphioxus by identifying nine
      anchor genes and sequencing both the anchor genes and the regions that flank them
      (a total of 400 kb). Phylogenetic analysis of 31 genes (including the anchor
      genes) in these regions shows that duplications occurred after the divergence of
      cephalochordates and vertebrates but before the Gnathostomata radiation. The
      distribution of human and amphioxus orthologs in their respective genomes and the
      relationship between these distributions support the en bloc duplication events.
      Our analysis represents the first step towards demonstrating that the human
      ancestral genome has undergone polyploidization. Moreover, reconstruction of the
      pre-duplicated region indicates that one of the duplicated regions retains the
      ancestral organization.

PMID- 11967532
TI  - Regulation of noise in the expression of a single gene.
AB  - Stochastic mechanisms are ubiquitous in biological systems. Biochemical reactions
      that involve small numbers of molecules are intrinsically noisy, being dominated
      by large concentration fluctuations. This intrinsic noise has been implicated in
      the random lysis/lysogeny decision of bacteriophage-lambda, in the loss of
      synchrony of circadian clocks and in the decrease of precision of cell signals.
      We sought to quantitatively investigate the extent to which the occurrence of
      molecular fluctuations within single cells (biochemical noise) could explain the
      variation of gene expression levels between cells in a genetically identical
      population (phenotypic noise). We have isolated the biochemical contribution to
      phenotypic noise from that of other noise sources by carrying out a series of
      differential measurements. We varied independently the rates of transcription and
      translation of a single fluorescent reporter gene in the chromosome of Bacillus
      subtilis, and we quantitatively measured the resulting changes in the phenotypic
      noise characteristics. We report that of these two parameters, increased
      translational efficiency is the predominant source of increased phenotypic noise.
      This effect is consistent with a stochastic model of gene expression in which
      proteins are produced in random and sharp bursts. Our results thus provide the
      first direct experimental evidence of the biochemical origin of phenotypic noise,
      demonstrating that the level of phenotypic variation in an isogenic population
      can be regulated by genetic parameters.

PMID- 11967533
TI  - Evidence of cis-acting factors in replication-mediated trinucleotide repeat
      instability in primate cells.
AB  - The mechanism of disease-associated trinucleotide repeat instability involves cis
      acting factors (cis-elements) in the vicinity of the repeat, but the nature of
      these elements is unknown. One cis-element may be the location of the replication
      origin relative to the repeat. We have used an SV40 DNA replication system to
      investigate the effect of the location of replication initiation on
      (CTG)(n)*(CAG)(n) stability in primate cells. Depending on the distance between
      the SV40 replication origin and the repeat tract, templates with 79 repeats yield
      predominantly expansions or predominantly deletions or remain intact. All
      templates with 17 repeats are stable. Thus, cis-elements that affect the sites of
      Okazaki fragment initiation relative to the repeat are crucial determinants of
      instability. This model system recapitulates the bias for expansions observed in
      many of the diseases associated with trinucleotide repeats. Our results might
      explain the variable amounts of CTG/CAG instability that are observed in
      different chromosomal contexts.

PMID- 11967534
TI  - Topological and causal structure of the yeast transcriptional regulatory network.
AB  - Interpretation of high-throughput biological data requires a knowledge of the
      design principles underlying the networks that sustain cellular functions. Of
      particular importance is the genetic network, a set of genes that interact
      through directed transcriptional regulation. Genes that exert a regulatory role
      encode dedicated transcription factors (hereafter referred to as regulating
      proteins) that can bind to specific DNA control regions of regulated genes to
      activate or inhibit their transcription. Regulated genes may themselves act in a
      regulatory manner, in which case they participate in a causal pathway. Looping
      pathways form feedback circuits. Because a gene can have several connections,
      circuits and pathways may crosslink and thus represent connected components. We
      have created a graph of 909 genetically or biochemically established interactions
      among 491 yeast genes. The number of regulating proteins per regulated gene has a
      narrow distribution with an exponential decay. The number of regulated genes per
      regulating protein has a broader distribution with a decay resembling a power
      law. Assuming in computer-generated graphs that gene connections fulfill these
      distributions but are otherwise random, the local clustering of connections and
      the number of short feedback circuits are largely underestimated. This deviation
      from randomness probably reflects functional constraints that include
      biosynthetic cost, response delay and differentiative and homeostatic regulation.

PMID- 11967535
TI  - Cardiac troponin T is essential in sarcomere assembly and cardiac contractility.
AB  - Mutations of the gene (TNNT2) encoding the thin-filament contractile protein
      cardiac troponin T are responsible for 15% of all cases of familial hypertrophic
      cardiomyopathy, the leading cause of sudden death in young athletes. Mutant
      proteins are thought to act through a dominant-negative mode that impairs
      function of heart muscle. TNNT2 mutations can also lead to dilated
      cardiomyopathy, a leading cause of heart failure. Despite the importance of
      cardiac troponin T in human disease, its loss-of-function phenotype has not been
      described. We show that the zebrafish silent heart (sih) mutation affects the
      gene tnnt2. We characterize two mutated alleles of sih that severely reduce tnnt2
      expression: one affects mRNA splicing, and the other affects gene transcription.
      Tnnt2, together with alpha-tropomyosin (Tpma) and cardiac troponins C and I
      (Tnni3), forms a calcium-sensitive regulatory complex within sarcomeres.
      Unexpectedly, in addition to loss of Tnnt2 expression in sih mutant hearts, we
      observed a significant reduction in Tpma and Tnni3, and consequently, severe
      sarcomere defects. This interdependence of thin-filament protein expression led
      us to postulate that some mutations in tnnt2 may trigger misregulation of thin
      filament protein expression, resulting in sarcomere loss and myocyte disarray,
      the life-threatening hallmarks of TNNT2 mutations in mice and humans.

PMID- 11967536
TI  - Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in
      noncarriers of BRCA1 or BRCA2 mutations.
AB  - Mutations in BRCA1 and BRCA2 confer a high risk of breast and ovarian cancer, but
      account for only a small fraction of breast cancer susceptibility. To find
      additional genes conferring susceptibility to breast cancer, we analyzed CHEK2
      (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is
      implicated in DNA repair processes involving BRCA1 and p53 (refs 3,4,5). We show
      that CHEK2(*)1100delC, a truncating variant that abrogates the kinase activity,
      has a frequency of 1.1% in healthy individuals. However, this variant is present
      in 5.1% of individuals with breast cancer from 718 families that do not carry
      mutations in BRCA1 or BRCA2 (P = 0.00000003), including 13.5% of individuals from
      families with male breast cancer (P = 0.00015). We estimate that the
      CHEK2(*)1100delC variant results in an approximately twofold increase of breast
      cancer risk in women and a tenfold increase of risk in men. By contrast, the
      variant confers no increased cancer risk in carriers of BRCA1 or BRCA2 mutations.
      This suggests that the biological mechanisms underlying the elevated risk of
      breast cancer in CHEK2 mutation carriers are already subverted in carriers of
      BRCA1 or BRCA2 mutations, which is consistent with participation of the encoded
      proteins in the same pathway.

PMID- 11967537
TI  - AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome
      9q34.
AB  - Congenital generalized lipodystrophy is an autosomal recessive disorder
      characterized by marked paucity of adipose tissue, extreme insulin resistance,
      hypertriglyceridemia, hepatic steatosis and early onset of diabetes. We report
      several different mutations of the gene (AGPAT2) encoding 1-acylglycerol-3
      phosphate O-acyltransferase 2 in 20 affected individuals from 11 pedigrees of
      diverse ethnicities showing linkage to chromosome 9q34. The AGPAT2 enzyme
      catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, a key
      intermediate in the biosynthesis of triacylglycerol and glycerophospholipids.
      AGPAT2 mRNA is highly expressed in adipose tissue. We conclude that mutations in
      AGPAT2 may cause congenital generalized lipodystrophy by inhibiting
      triacylglycerol synthesis and storage in adipocytes.

PMID- 11967538
TI  - Network motifs in the transcriptional regulation network of Escherichia coli.
AB  - Little is known about the design principles of transcriptional regulation
      networks that control gene expression in cells. Recent advances in data
      collection and analysis, however, are generating unprecedented amounts of
      information about gene regulation networks. To understand these complex wiring
      diagrams, we sought to break down such networks into basic building blocks. We
      generalize the notion of motifs, widely used for sequence analysis, to the level
      of networks. We define 'network motifs' as patterns of interconnections that
      recur in many different parts of a network at frequencies much higher than those
      found in randomized networks. We applied new algorithms for systematically
      detecting network motifs to one of the best-characterized regulation networks,
      that of direct transcriptional interactions in Escherichia coli. We find that
      much of the network is composed of repeated appearances of three highly
      significant motifs. Each network motif has a specific function in determining
      gene expression, such as generating temporal expression programs and governing
      the responses to fluctuating external signals. The motif structure also allows an
      easily interpretable view of the entire known transcriptional network of the
      organism. This approach may help define the basic computational elements of other
      biological networks.

PMID- 11967539
TI  - Disruption of CREB function in brain leads to neurodegeneration.
AB  - Control of cellular survival and proliferation is dependent on extracellular
      signals and is a prerequisite for ordered tissue development and maintenance.
      Activation of the cAMP responsive element binding protein (CREB) by
      phosphorylation has been implicated in the survival of mammalian cells. To define
      its roles in the mouse central nervous system, we disrupted Creb1 in brain of
      developing and adult mice using the Cre/loxP system. Mice with a Crem(-/-)
      background and lacking Creb in the central nervous system during development show
      extensive apoptosis of postmitotic neurons. By contrast, mice in which both Creb1
      and Crem are disrupted in the postnatal forebrain show progressive
      neurodegeneration in the hippocampus and in the dorsolateral striatum. The
      striatal phenotype is reminiscent of Huntington disease and is consistent with
      the postulated role of CREB-mediated signaling in polyglutamine-triggered
      diseases.

PMID- 11967540
TI  - Essential roles of the kappa light chain intronic enhancer and 3' enhancer in
      kappa rearrangement and demethylation.
AB  - The kappa intronic (MiE(kappa)) and 3' (3'E(kappa)) enhancers are both
      quantitatively important to, but not essential for, immunoglobulin kappa
      rearrangement. To determine the functional redundancy between these two
      enhancers, B cells derived from mutant embryonic stem cells--in which both
      MiE(kappa) and 3'E(kappa) were deleted on both kappa alleles--were analyzed for
      kappa rearrangement. Our findings indicate that these double-mutant B cells have
      essentially no kappa rearrangement but do rearrange and express lambda.
      Therefore, these two kappa enhancers share essential roles in activating
      V(kappa)J(kappa) rearrangement. Our findings also indicate that the two kappa
      enhancers play overlapping and distinct roles in the demethylation of kappa in B
      cells.

PMID- 11967541
TI  - Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+)
      thymocytes.
AB  - T cell receptor (TCR) alpha alleles undergo primary and secondary rearrangement
      in double-positive (DP) thymocytes. By analyzing TCRalpha rearrangement in orphan
      nuclear receptor RORgamma-deficient mice, in which the DP lifespan is shorter,
      and in Bcl-x(L)-transgenic mice, in which the DP lifespan is extended, we show
      that the progression of secondary V(alpha) to J(alpha) rearrangements is
      controlled by DP thymocyte survival. In addition, because Bcl-x(L) induces a bias
      towards 3' J(alpha) usage in peripheral T cells, we conclude that the programmed
      cell death of DP thymocytes is not simply a consequence of failed positive
      selection. Rather, it limits the progression of rearrangement along the J(alpha)
      locus and the opportunities for positive selection, thereby regulating the
      TCRalpha repertoire.

PMID- 11967543
TI  - Notch-RBP-J signaling is involved in cell fate determination of marginal zone B
      cells.
AB  - RBP-J is a key mediator of Notch signaling that regulates cell fate determination
      in various lineages. To investigate the function of Notch-RBP-J in mature B cell
      differentiation, we generated mice that selectively lacked B cell RBP-J
      expression using conditional mutagenesis. Absence of RBP-J led to the loss of
      marginal zone B (MZB) cells with a concomitant increase in follicular B cells; in
      contrast, B1 cells in the peritoneal cavity were unaffected. Lack of RBP-J caused
      no defects in B cells maintenance, survival, plasma cell differentiation or
      activation. It is therefore likely that Notch-RBP-J signaling regulates the
      lineage commitment of mature B cells into follicular versus MZB cells. In
      addition, in mice with RBP-J-deficient B cells, had no obvious changes in
      immunoglobulin production in response to Ficoll, lipopolysaccharide or chicken
      gammaglobulin. In contrast, these mice exhibited increased mortality rates after
      blood-borne bacterial infection, which indicates that MZB cells play pivotal
      roles in the clearance of these bacteria.

PMID- 11967542
TI  - The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived
      plasma cells.
AB  - Affinity maturation of the immune response and the generation of long-lived bone
      marrow (BM) plasma cells are hallmarks of CD40-dependent, thymus-dependent (TD)
      humoral immunity. Through disruption of the tumor necrosis factor receptor (TNFR)
      associated factor 6 (TRAF6)-binding site within the CD40 cytoplasmic domain, we
      selectively ablated affinity maturation and the generation of plasma cells after
      immunization. Mutagenesis of both the TRAF6 and TRAF2-TRAF3 sites was essential
      for arresting germinal center formation in response to immunization. CD40-induced
      B cell proliferation and early immunoglobulin production occurred even when all
      TRAF sites were ablated. These studies show that specific CD40-TRAF associations
      control well defined aspects of humoral immunity. In addition, they define the
      roles that TRAF-dependent and TRAF-independent pathways play in regulating
      antigen-driven B cell differentiation.

PMID- 11967544
TI  - A specialization for relative disparity in V2.
AB  - Stereoscopic depth perception relies on binocular disparities, or small geometric
      differences between the retinal images of each eye. The most reliable binocular
      depth judgments are those that are based on relative disparities between two
      simultaneously visible features in a scene. Many cortical areas contain neurons
      that are sensitive to disparity, but it is unclear whether any areas show a
      specific sensitivity to relative disparity. We recorded from neurons in the early
      cortical visual area V2 of the awake macaque during presentation of random-dot
      patterns. The depth of a central region ('center'), and that of an annular
      surrounding region ('surround'), were manipulated independently in these stimuli.
      Some cells were fully selective for the resulting relative disparities. Most
      showed partial selectivity, which nonetheless indicated a sensitivity for the
      depth relationship between center and surround. Both types of neural response
      could support psychophysical judgments of relative depth.

PMID- 11967545
TI  - Multiple levels of visual object constancy revealed by event-related fMRI of
      repetition priming.
AB  - We conducted two event-related functional magnetic resonance imaging (fMRI)
      experiments to investigate the neural substrates of visual object recognition in
      humans. We used a repetition-priming method with visual stimuli recurring at
      unpredictable intervals, either with the same appearance or with changes in size,
      viewpoint or exemplar. Lateral occipital and posterior inferior temporal cortex
      showed lower activity for repetitions of both real and non-sense objects;
      fusiform and left inferior frontal regions showed decreases for repetitions of
      only real objects. Repetition of different exemplars with the same name affected
      only the left inferior frontal cortex. Crucially, priming-induced decreases in
      activity of the right fusiform cortex depended on whether the three-dimensional
      objects were repeated with the same viewpoint, regardless of whether retinal
      image size changed; left fusiform decreases were independent of both viewpoint
      and size. These data show that dissociable subsystems in ventral visual cortex
      maintain distinct view-dependent and view-invariant object representations.

PMID- 11967546
TI  - Receptive-field construction in cortical inhibitory interneurons.
AB  - In the somatosensory 'barrel' cortex (where each barrel represents an individual
      whisker) the receptive fields of cortical spiny neurons show considerable
      specificity for the direction of whisker displacement, as do the receptive fields
      of thalamocortical (TC) neurons that provide input to the barrels. In contrast,
      putative fast-spike inhibitory interneurons in layer 4 of the barrel cortex lack
      directional preference, but are exquisitely sensitive to low stimulus
      intensities. Here we show, in adult rabbits, that these sensitive and broadly
      tuned inhibitory receptive fields are generated by an unselective pooling of
      convergent functional inputs from topographically aligned TC neurons with very
      diverse response properties.

PMID- 11967547
TI  - Chemosensitive serotonergic neurons are closely associated with large medullary
      arteries.
AB  - We have previously shown that serotonergic neurons of the medulla are strongly
      stimulated by an increase in CO(2), suggesting that they are central respiratory
      chemoreceptors. Here we used confocal imaging and electron microscopy to show
      that neurons immunoreactive for tryptophan hydroxylase (TpOH) are tightly apposed
      to large arteries in the rat medulla. We used patch-clamp recordings from brain
      slices to confirm that neurons with this anatomical specialization are
      chemosensitive. Serotonergic neurons are ideally situated for sensing arterial
      blood CO(2), and may help maintain pH homeostasis via wide-ranging effects on
      brain function. The results reported here support a recent proposal that sudden
      infant death syndrome (SIDS) results from a developmental abnormality of
      medullary serotonergic neurons.

PMID- 11967548
TI  - Acute versus chronic NMDA receptor blockade and synaptic AMPA receptor delivery.

PMID- 11967549
TI  - Experimental tests of the adaptive significance of sexual recombination.
AB  - Numerous theories have been proposed to explain the advantages of sexual
      recombination   the exchange of hereditary material between different genomes or
      homologous chromosomes. Many of these candidate benefits have been evaluated in
      controlled laboratory experiments, which, collectively, strongly indicate that
      sexual recombination provides important long-term advantages.

PMID- 11967550
TI  - Resolving the paradox of sex and recombination.
AB  - Sexual reproduction and recombination are ubiquitous. However, a large body of
      theoretical work has shown that these processes should only evolve under a
      restricted set of conditions. New studies indicate that this discrepancy might
      result from the fact that previous models have ignored important complexities
      that face natural populations, such as genetic drift and the spatial structure of
      populations.

PMID- 11967551
TI  - Postcopulatory sexual selection.
AB  - The female reproductive tract is where competition between the sperm of different
      males takes place, aided and abetted by the female herself. Intense
      postcopulatory sexual selection fosters inter-sexual conflict and drives rapid
      evolutionary change to generate a startling diversity of morphological,
      behavioural and physiological adaptations. We identify three main issues that
      should be resolved to advance our understanding of postcopulatory sexual
      selection. We need to determine the genetic basis of different male fertility
      traits and female traits that mediate sperm selection; identify the genes or
      genomic regions that control these traits; and establish the coevolutionary
      trajectory of sexes.

PMID- 11967552
TI  - The evolution of plant sexual diversity.
AB  - Charles Darwin recognized that flowering plants have an unrivalled diversity of
      sexual systems. Determining the ecological and genetic factors that govern sexual
      diversification in plants is today a central problem in evolutionary biology. The
      integration of phylogenetic, ecological and population-genetic studies have
      provided new insights into the selective mechanisms that are responsible for
      major evolutionary transitions between reproductive modes.

PMID- 11967553
TI  - Listening to silence and understanding nonsense: exonic mutations that affect
      splicing.
AB  - Point mutations in the coding regions of genes are commonly assumed to exert
      their effects by altering single amino acids in the encoded proteins. However,
      there is increasing evidence that many human disease genes harbour exonic
      mutations that affect pre-mRNA splicing. Nonsense, missense and even
      translationally silent mutations can inactivate genes by inducing the splicing
      machinery to skip the mutant exons. Similarly, coding-region single-nucleotide
      polymorphisms might cause phenotypic variability by influencing splicing accuracy
      or efficiency. As the splicing mechanisms that depend on exonic signals are
      elucidated, new therapeutic approaches to treating certain genetic diseases can
      begin to be explored.

PMID- 11967554
TI  - Patterns of linkage disequilibrium in the human genome.
AB  - Particular alleles at neighbouring loci tend to be co-inherited. For tightly
      linked loci, this might lead to associations between alleles in the population  
      a property known as linkage disequilibrium (LD). LD has recently become the focus
      of intense study in the hope that it might facilitate the mapping of complex
      disease loci through whole-genome association studies. This approach depends
      crucially on the patterns of LD in the human genome. In this review, we draw on
      empirical studies in humans and Drosophila, as well as simulation studies, to
      assess the current state of knowledge about patterns of LD, and consider the
      implications for the use of LD as a mapping tool.

PMID- 11967555
TI  - Evolution of sex: The costs and benefits of sex: new insights from old asexual
      lineages.
AB  - Discussions that are aimed at understanding the maintenance of sexual
      reproduction are in a bit of a quagmire owing to the many competing theories that
      have been proposed. Also, one of the central observations   that asexual lineages
      are typically short lived   still needs to be properly quantified. Exciting new
      results on ancient asexual organisms show that lineages can persist for many
      millions of generations without recombination. Understanding how they do so might
      well provide crucial new insights into the problem of sex.

PMID- 11967556
TI  - Neural correlates of consciousness in humans.

PMID- 11967557
TI  - Neural induction, the default model and embryonic stem cells.

PMID- 11967558
TI  - gamma-Secretase, Notch, Abeta and Alzheimer's disease: where do the presenilins
      fit in?

PMID- 11967559
TI  - New concepts in the immunopathogenesis of multiple sclerosis.

PMID- 11967560
TI  - Neuroimage databases: the good, the bad and the ugly.

PMID- 11967561
TI  - Opinion: Sharing primary data: a threat or asset to discovery?

PMID- 11967562
TI  - Opinion: Databasing fMRI studies towards a 'discovery science' of brain function.

PMID- 11967563
TI  - Opinion: Mapping context and content: the BrainMap model.

PMID- 11967564
TI  - Opinion: Localization in the brain: new solutions emerging.

PMID- 11967565
TI  - Structural insights into CPT-11 activation by mammalian carboxylesterases.
AB  - Mammalian carboxylesterases cleave the anticancer prodrug CPT-11 (Irinotecan)
      into SN-38, a potent topoisomerase I poison, and 4-piperidino-piperidine (4PP).
      We present the 2.5 A crystal structure of rabbit liver carboxylesterase (rCE),
      the most efficient enzyme known to activate CPT-11 in this manner, in complex
      with the leaving group 4PP. 4PP is observed bound adjacent to a high-mannose Asn
      linked glycosylation site on the surface of rCE. This product-binding site is
      separated from the catalytic gorge by a thin wall of amino acid side chains,
      suggesting that 4PP may be released through this secondary product exit pore. The
      crystallographic observation of a leaving group bound on the surface of rCE
      supports the 'back door' product exit site proposed for the
      acetylcholinesterases. These results may facilitate the design of improved
      anticancer drugs or enzymes for use in viral-directed cancer cotherapies.

PMID- 11967566
TI  - Structural properties of an amyloid precursor of beta(2)-microglobulin.
AB  - The population of one or more partially folded states has been proposed as a
      critical initial step in amyloid formation for several proteins. Here we use
      equilibrium denaturation measured by (1)H-(15)N NMR to determine the
      conformational properties of an amyloidogenic intermediate of human beta(2)
      microglobulin (beta(2)m) formed at low pH. The data show that this amyloid
      precursor is a noncooperatively stabilized ensemble that retains stable structure
      in five of the seven beta-strands that comprise the native fold. The amyloid
      precursors of beta(2)m and transthyretin have similar properties despite having
      structurally unrelated native folds. The data offer a rationale as to why these
      proteins are both amyloidogenic at low pH and suggest that amyloidosis of these
      and other proteins may involve ordered assembly from a precursor with similar
      conformational features.

PMID- 11967567
TI  - Mapping the core of the beta(2)-microglobulin amyloid fibril by H/D exchange.
AB  - Despite numerous efforts, the lack of detailed structural information on amyloid
      fibrils has hindered clarification of the mechanism of their formation. Here, we
      describe a novel procedure for characterizing the conformational flexibility of
      beta(2)-microglobulin amyloid fibrils at single-residue resolution that uses H/D
      exchange of amide protons combined with NMR analysis. The results indicate that
      most residues in the middle region of the molecule, including the loop regions in
      the native structure, form a rigid beta-sheet core, whereas the the N- and C
      termini are excluded from this core. The extensively hydrogen-bonded beta-sheet
      core explains the remarkable rigidity and stability of amyloid fibrils. The
      present method could be used to obtain residue-specific conformational
      information of various amyloid fibrils, even though it does not provide a high
      resolution three-dimensional structure.

PMID- 11967568
TI  - The crystal structure of the mouse apoptosis-inducing factor AIF.
AB  - Mitochondria play a key role in apoptosis due to their capacity to release
      potentially lethal proteins. One of these latent death factors is cytochrome c,
      which can stimulate the proteolytic activation of caspase zymogens. Another
      important protein is apoptosis-inducing factor (AIF), a flavoprotein that can
      stimulate a caspase-independent cell-death pathway required for early embryonic
      morphogenesis. Here, we report the crystal structure of mouse AIF at 2.0 A. Its
      active site structure and redox properties suggest that AIF functions as an
      electron transferase with a mechanism similar to that of the bacterial ferredoxin
      reductases, its closest evolutionary homologs. However, AIF structurally differs
      from these proteins in some essential features, including a long insertion in a C
      terminal beta-hairpin loop, which may be related to its apoptogenic functions.

PMID- 11967570
TI  - [New Drugs: Ectasy and Gamma-Hydroxy-Butyrate (GHB)].
AB  - For several years the "raves" and "tecno" parties are accompanied of a growing
      consumption of such substances as Ecstasy and Gamma-Hidroxi-Butirato (GHB). In
      this article, their authors describe the secondary and toxic effects of those
      drugs. These data should alert about the risk of considering this new way of
      substance abuse as a banal fact.

PMID- 11967569
TI  - Structural insights into the pro-apoptotic function of mitochondrial serine
      protease HtrA2/Omi.
AB  - HtrA2/Omi, a mitochondrial serine protease in mammals, is important in programmed
      cell death. However, the underlining mechanism of HtrA2/Omi-mediated apoptosis
      remains unclear. Analogous to the bacterial homolog HtrA (DegP), the mature HtrA2
      protein contains a central serine protease domain and a C-terminal PDZ domain.
      The 2.0 A crystal structure of HtrA2/Omi reveals the formation of a pyramid
      shaped homotrimer mediated exclusively by the serine protease domains. The
      peptide-binding pocket of the PDZ domain is buried in the intimate interface
      between the PDZ and the protease domains. Mutational analysis reveals that the
      monomeric HtrA2/Omi mutants are unable to induce cell death and are deficient in
      protease activity. The PDZ domain modulates HtrA2/Omi-mediated cell death
      activity by regulating its serine protease activity. These structural and
      biochemical observations provide an important framework for deciphering the
      mechanisms of HtrA2/Omi-mediated apoptosis.

PMID- 11967571
TI  - [Mental Health Residents: Knowledge on prices and availability of drugs they
      prescribe].
AB  - OBJECTIVES: The cost and availability of psychiatric drugs is an important aspect
      for patient adherence to treatment. Therefore, Psychiatry Residents were
      interviewed about what drugs were most usually prescribed by them, their
      estimated price, free availability in their hospitals and access to literature
      about drug costs in the services. MATERIALS AND METHODS: During the VI Congress
      of Residents in Mental Health of the Metropolitan Area of Buenos Aires, a
      structured interview was administered to Psychiatry Residents. A form was used
      containing open and close questions. The questionnaire was not self administered.
      Sixty eight Psychiatry Residents of fourteen Public Hospitals of the Capital and
      Province of Buenos Aires were interviewed. RESULTS: The drugs most frequently
      chosen in each pharmacological group were: haloperidol 24 percent, fluoxetine 43
      per cent, clonazepan 39 percent and carbamazepine 34 per cent 82 percent of the
      questions regarding the knowledge about prescribed drug costs were incorrect. 57
      per cent of the drugs chosen were not available at the Hospitals whereas 69 per
      cent of the drugs that were never selected were available. CONCLUSIONS: In this
      descriptive study, we found an important lack of knowledge on drug costs, little
      access to literature about this subject and availability of drugs not adequated
      to the Residents choices.

PMID- 11967572
TI  - [Biomedicine or anthropological medicine].
AB  - The huge developments in the biological research and in the technics used in
      other spheres of science (physics, mathematics, chemistry, cybernetics, etc.)
      have a great influence on the constitution of the actual medical paradigm, as
      well as other non strictly scientific factors. These external factors are
      economic, political and cultural ones -such as the pharmaceutical industry and
      the public health systems, the privatisation of health services, the large amount
      of professionals, the advances in the medical instruments, etc. The theoritician
      of the Heidelberg School, called this prevalent model "biomedical" or "natural
      scientific", underlying this way the tendance to the biological reductionism in
      relation to the concept of "illness" thus excluding the subjectivity, the history
      and the sociability of the patient when dealing with the pain, the inability and
      the death. Since the middle of XXth Century a serious criticism of this medical
      paradigm has been raised. This criticism revolved around the so called
      anthropological or integral model. This article makes a revision of this problem
      from a historical and epistemological outlook, revisiting some specific features
      in the psychiatric field.

PMID- 11967573
TI  - [Subjetivity and interconsultation in front of the new pathologies and
      technologies].
AB  - The technological advance in medicine was accompanied paradoxically of a lack of
      consideration toward the human being subjective dimension. This resulted in the
      appearance of new and unexpected inconveniences, caused by the patient's
      attitudes that cannot be understood neither solved by the specialist doctors,
      hindering the application of important achieved advantages. This development is
      particularly remarkable in the most spectacular innovations (transplantation and
      reimplantation of organs, protesis, electronic ortesis, hormonal substitutions,
      chemotherapy, etc.) that can mean the difference between life and death. There
      are human and subjective motivations behind all these problems that have not been
      kept in mind although constitute the specific sphere of work and investigation of
      the medical-psychological interconsultation.

PMID- 11967574
TI  - [Psychiatry and HIV].
AB  - Are there specific psychiatric issues in the treatment of human immunodeficiency
      virus (HIV) that force us to modify our typical model of care delivery in most
      communities? This appears to be the case. Most of these issues stem from the fact
      that the HIV-positive population has a high prevalence of a variety of
      psychiatric disorders. The integration of the psychiatric treatment with general
      medical treatment improves psychiatric and medical outcomes. Along this lines,
      how con understanding personality types improve our ability to prevent and treat
      human immunodeficiency virus (HIV) Some people are far more likely to indulge in
      risky behavior than others. The human immunodeficiency virus (HIV) epidemic is
      driven by high-risk behaviors that are often associated with psychiatric
      disorders. Because of this, psychiatrists have an important role in the treatment
      and prevention of HIV. Furthermore, the current treatment for HIV requires strict
      adherence to complicated regimens, and untreated psychiatric disorders are a
      major barrier to effective treatment. Individuals who are "unstable" and/or
      "extroverted" make up the greatest group of patients in acquired immunodeficiency
      syndrome (AIDS) clinics. Understanding the dynamics of their character leads to
      better therapeutic approaches in their treatment. A cognitive behavioral approach
      that 1) focuses on thoughts instead of feelings, 2) uses a "behavioral contract",
      3) emphasizes rewards, and 4) involves coordination with medical care providers,
      has been found effective in treating AIDS patients who are especially at risk.

PMID- 11967575
TI  - [From the HIV body to the ARV body].
AB  - The current HIV subjectivity lies on two great enunciative categories: HIV body,
      raised from Aids epidemic former stage, catheterized by being the viral genius
      development place. This omnipotent structure appears untouched of medical
      interdiction. And the ARV body, identified to H.A.A.R.T regime drugs adherence,
      and to horizontal and vertical machinic flows as well. These categories obtained
      from Flix Guattari's thoughts, are placed like theoretical framework for
      predicting of adherence achievement.

PMID- 11967576
TI  - [Incidence of the therapeutic advances in children and adolescents that suffered
      cancer].
AB  - This article intends to consider some aspects of the long term effects in the
      children and adolescents who suffered cancer and the impact that the new
      technologies and treatments produce.

PMID- 11967577
TI  - [Which is the demand for psychiatric and psychological interconsultation when the
      patient has cancer?].
AB  - The intervention of the professionals of mental health in the sphere of the
      oncology goes hand in hand with the advance that has been generated in the
      treatment of the oncological illnesses. This way patient's life is prolonged.
      This development gives place to a whole set of new problems for the patient, his
      family and the team of health professionals that have been caring him until the
      moment. 68 percent of the patients suffering cancer has dysfunctions of
      adaptation in some moment in the course of its illness. Between a 25 and 40
      percent, depending on the characteristics of the sample, present a depressive
      disorder according to the criteria of the DSM-IV. Finally, the presence of
      delirium is very likely in around the 15 percent of the patients in general, in
      25 percent of the aging and in 75 percent of the patients that are in the last
      stages of their illness.

PMID- 11967578
TI  - [Psychosomatic emphasis in medicine].

PMID- 11967579
TI  - [The thinking and the doing of the psychoanalytical psychologist of today].

PMID- 11967580
TI  - [Interview with Kennet Schulman].

PMID- 11967581
TI  - Implications of the hemodynamic optimization approach guided by right heart
      catheterization in patients with severe heart failure.
AB  - OBJECTIVE: To report the hemodynamic and functional responses obtained with
      clinical optimization guided by hemodynamic parameters in patients with severe
      and refractory heart failure. METHODS: Invasive hemodynamic monitoring using
      right heart catheterization aimed to reach low filling pressures and peripheral
      resistance. Frequent adjustments of intravenous diuretics and vasodilators were
      performed according to the hemodynamic measurements. RESULTS: We assessed 19
      patients (age = 48+/-12 years and ejection fraction = 21+/-5%) with severe heart
      failure. The intravenous use of diuretics and vasodilators reduced by 12 mm Hg
      (relative reduction of 43%) pulmonary artery occlusion pressure (P<0.001), with a
      concomitant increment of 6 mL per beat in stroke volume (relative increment of
      24%, P<0.001). We observed significant associations between pulmonary artery
      occlusion pressure and mean pulmonary artery pressure (r=0.76; P<0.001) and
      central venous pressure (r=0.63; P<0.001). After clinical optimization,
      improvement in functional class occurred (P< 0.001), with a tendency towards
      improvement in ejection fraction and no impairment to renal function. CONCLUSION:
      Optimization guided by hemodynamic parameters in patients with refractory heart
      failure provides a significant improvement in the hemodynamic profile with
      concomitant improvement in functional class. This study emphasizes that
      adjustments in blood volume result in immediate benefits for patients with severe
      heart failure.

PMID- 11967582
TI  - Electrocardiographic alterations in patients hospitalized with leptospirosis in
      the Brazilian city of Salvador.
AB  - OBJECTIVE: To report the frequency and types of electrocardiographic alterations
      in patients with leptospirosis in the first 24 hours of hospitalization. METHODS:
      We analyzed the electrocardiograms of 157 patients admitted to the Hospital Couto
      Maia in the city of Salvador, in the State of Bahia, Brazil, from March 1998 to
      June 1999. The electrocardiograms were performed in the first 24 hours after
      hospital admission, independent of the clinical manifestations of the patients.
      RESULTS: The mean +/- SD for patients' age was 35.5+/- 13.7 (median = 32) years,
      and jaundice was present in 95.5% of them. Alterations in the electrocardiogram
      were detected in 68.2% (107/157) of the patients (95% confidence interval = 60.6%
      - 75.1%). Atrial fibrillation was the most frequent arrhythmia, occurring in
      10.8% (17/157) of the patients. Other frequent findings were alterations in
      ventricular repolarization detected in 38.9% (61/157) of patients and first
      degree atrioventricular block in 10.2% (16/157). The patients with atrial
      fibrillation were older and had higher levels of creatinine and
      aminotransferases. CONCLUSION: In this sample, approximately 2/3 of the patients
      had electrocardiographic alterations after hospital admission. Of the major
      arrhythmias, atrial fibrillation was the most frequent, and the patients with
      this arrhythmia had evidence of more severe disease. The relation between the
      presence and type of electrocardiographic alteration and the prognosis of
      leptospirosis is yet to be assessed.

PMID- 11967583
TI  - The need for pedagogical qualifications for teaching cardiology to undergraduate
      students.
AB  - OBJECTIVE: To report a training program in cardiology emphasizing changes in its
      pedagogical practice. These changes were put into practice by some teachers at
      the Medical School of Porto Alegre of the University of Rio Grande do Sul
      (FAMED/UFRGS) aiming to make faculty and student activities more dynamic and to
      promote more efficacious learning. The training program is directed at 5th
      semester medical students and aims at a behavioral change in teachers and
      students to promote more interaction, to favor exchanges, and to make the
      teaching-learning process easier, always maintaining the patient in the center of
      the medical activity. METHODS: The program emphasizes the definition of general
      and specific objectives for each activity to be developed by the students, with
      training in the area of admission to the cardiology service, with special
      emphasis on behavioral change in the cognitive, motor, affective, and attitudinal
      areas. Knowledge was developed by means of interactive seminars with initial and
      final assessment tests to identify students' and teachers' performance. The
      students were evaluated in an immediate, continuous, and progressive way in their
      daily activities and through comparison of the results of 2 tests, one applied at
      the beginning of the training and the other at its end. These 2 tests contained
      the same questions. RESULTS: We systematically assessed 560 students over 4
      years. The mean grades of the tests performed prior to and after the 244 seminars
      were 7.38+/-1.66 and 9.17+/- 0.82, respectively (p<0.0001). For the tests applied
      at the beginning and at the end of the training, the mean grades were 5.61+/-1.61
      and 9.37+/-0.90, respectively (p<0.0001). CONCLUSION: The program proved to be
      efficient both for the students' learning and for assessing their performance in
      a systematic and objective way.

PMID- 11967584
TI  - Study of coronary flow reserve with intravenous use of microbubbles (contrast
      echocardiography) and adenosine: protocol for clinical application in patients
      suspected of having coronary heart disease.
AB  - OBJECTIVE: To test the feasibility, safety and accuracy of the adenosine protocol
      in the study of myocardial perfusion with microbubbles contrast echocardiography.
      METHODS: 81 pts (64 male, 60+11 years) were submitted to contrast
      echocardiography with PESDA (sonicated solution of albumin 20%-1ml, dextrose 5%
      12ml and deca-fluorobutane gas-8ml) to study the myocardial perfusion at rest and
      after bolus injection of adenosine (6 to 18mg) and to coronary angiography within
      1 month each other. For each patient 3 left ventricle perfusion beds were
      considered (total of 243 territories). 208 territories were analyzed and 35
      territories were excluded. PESDA was continuously infused (1-2ml/min), titrated
      for best myocardial contrast. Triggered (1:1) second harmonic imaging was used.
      RESULTS: Coronary angiography showed 70 flow limiting (> 75%) lesions and 138 no
      flow limiting lesions. At rest an obvious myocardium contrast enhancement was
      seen in at least 1 segment of a territory in all patients. After adenosine
      injection an unquestionable further increase in myocardial contrast was observed
      in 136 territories (99%) related to no flow limiting lesions, lasting < 10 s, and
      a myocardial perfusion defect was detected in 68 territories (97%) related to
      flow limiting lesions. It was observed only 4 false results. There were no
      serious complications. CONCLUSION: Myocardial perfusion study with PESDA and
      adenosine protocol is a practical, safe and accurate method to analyze the
      coronary flow reserve.

PMID- 11967585
TI  - Effect of propafenone on the contractile activity of Latissimus dorsi muscle
      isolated in an organ chamber: experimental study in rats.
AB  - OBJECTIVE: To study the effect of propafenone on the contractile function of
      latissimus dorsi muscle isolated from rats in an organ chamber. METHODS: We
      studied 20 latissimus dorsi muscles of Wistar rats and divided them into 2
      groups: group I (n=10), or control group - we studied the feasibility of muscle
      contractility; group II (n=10), in which the contralateral muscles were grouped -
      we analyzed the effect of propafenone on muscle contractility. After building a
      muscle ring, 8 periods of sequential 2-minute baths were performed, with
      intervals of preprogrammed electrical stimulation using a pacemaker of 50
      stimuli/min. In group II, propafenone, at the concentration of 9.8 microgram/mL,
      was added to the bath in period 2 and withdrawn in period 4. RESULTS: In group I,
      no significant depression in muscle contraction occurred up to period 5 (p>0.05).
      In group II, a significant depression occurred in all periods, except between the
      last 2 periods (p<0.05). Comparing groups I and II only in period 1, which was a
      standard period for both groups, we found no significant difference (p>0.05).
      CONCLUSION: Propafenone had a depressing effect on the contractile function of
      latissimus dorsi muscle isolated from rats and studied in an organ chamber.

PMID- 11967586
TI  - Anomalous origin of the left coronary artery from the pulmonary artery: report of
      an adult case.
AB  - We report the clinical findings, pathophysiology, diagnostic characteristics, and
      surgical repair of anomalous origin of the left coronary artery from the
      pulmonary artery in a 26-year-old female patient with a clinical diagnosis of
      coronary heart disease.

PMID- 11967587
TI  - A new use for the amplatzer duct occluder device.
AB  - We report a case in which the Amplatzer device for percutaneous occlusion of
      ductus arteriosus was successfully used for occluding a large systemic-pulmonary
      collateral vessel in a patient who had previously undergone surgery for
      correction of pulmonary atresia and ventricular septal defect (Rastelli
      technique), and was awaiting the change of a cardiac tube. In the first attempt,
      the device embolized to the distal pulmonary bed and, after being rescued with a
      Bitome, it was appropriately repositioned with no complications and with total
      occlusion of the vessel.

PMID- 11967588
TI  - MV causes lung inflammation and systemic immune depression. A balance of fire and
      ice.

PMID- 11967589
TI  - Functional hemodynamic monitoring.

PMID- 11967590
TI  - Intra-abdominal pressure: time for clinical practice guidelines?

PMID- 11967591
TI  - Stroke volume variations for assessment of cardiac responsiveness to volume
      loading in mechanically ventilated patients after cardiac surgery.
AB  - OBJECTIVE: We hypothesized that measuring stroke volume variation (SVV) during
      mechanical ventilation by continuous arterial pulse contour analysis allows the
      accurate prediction and monitoring of changes in cardiac index (CI) in response
      to volume administration. DESIGN AND SETTING: Prospective study in an university
      hospital. PATIENTS: Twenty mechanically ventilated patients following cardiac
      surgery. INTERVENTIONS: Volume loading with oxypolygelatin (3.5%) 20 ml x body
      mass index over 10 min. MEASUREMENTS AND RESULTS: SVV, central venous pressure
      (CVP), pulmonary artery occlusion pressure (PAOP), left ventricular end-diastolic
      area index (LVEDAI) by transesophageal echocardiography, intrathoracic blood
      volume index (ITBVI) by transpulmonary thermodilution and CI were determined
      immediately before and after volume loading. SVV decreased, while CI, CVP, PAOP,
      ITBVI, and LVEDAI increased significantly. Percentage changes in CI were
      significantly correlated to percentage changes in SVV (r(2)=-0.59, p<0.001),
      ITBVI (r(2)=0.79, p<0.001), and PAOP (r(2)=0.33, p<0.05) and to baseline values
      of SVV (r(2)=0.55, p<0.05) and LVEDAI (r(2)=-0.68, p<0.001). CONCLUSIONS: SVV may
      help to determine the preload condition of ventilated patients following cardiac
      surgery and to predict and continuously monitor effects of volume administered as
      part of their hemodynamic management.

PMID- 11967592
TI  - Cardiac output measurement by pulse dye densitometry: a comparison with the
      Fick's principle and thermodilution method.
AB  - OBJECTIVE: To evaluate the agreement between cardiac output (CO) measurements
      obtained by a new dye dilution technique using pulse dye densitometry (PDD) and
      thermodilution (TD) and the direct Fick method (F). DESIGN AND SETTING:
      Prospective clinical study in a university hospital, cardiac surgery intensive
      care unit. PATIENTS: Fifty-eight cardiac surgery patients after admission to the
      intensive care unit (six were excluded due to a low pulse signal quality using
      the PDD method). MEASUREMENTS AND RESULTS: Mean CO was 5.3+/-1.8 l/min for PDD,
      5.7+/-1.68 l/min for TD, and 6.16+/-1.66 l/min for F. There was a good
      correlation between PDD and TD ( r(2)=0.93) and between PDD and F ( r(2)=0.77).
      Bias and precision between PDD and TD were -0.39+/-0.5 l/min and -0.69+/-0.85
      l/min between PDD and F. In general, PDD determined lower CO values than TD and
      F. Especially in patients with CO below 5 l/min PDD underestimated CO in
      comparison to TD and F (bias and precision: -0.51+/-0.40 l/min and -0.83+/-1.0
      l/min). CONCLUSION: Comparison between PDD and TD showed good agreement for the
      normal to high CO range. However, agreement was poor in patients with low CO. In
      the latter patient group PDD showed relevant underestimation of CO compared to TD
      and F. Due to these limitations PDD cannot entirely replace the pulmonary artery
      catheter for CO determination.

PMID- 11967593
TI  - Relationship between ventilatory settings and barotrauma in the acute respiratory
      distress syndrome.
AB  - OBJECTIVE: High pressures or volumes may increase the risk of barotrauma in the
      acute respiratory distress syndrome (ARDS). METHODS: The first part of the study
      analyzed data from a prospective trial of two ventilation strategies in 116
      patients with ARDS retrospectively, and ventilatory pressures and volumes were
      compared in patients with or without pneumothorax. The second part consisted of a
      literature analysis of prospective trials (14 clinical studies, 2270 patients)
      describing incidence and risk factors for barotrauma in ARDS patients, and mean
      values of ventilatory parameters were plotted against incidence of barotrauma.
      RESULTS: In our clinical trial comparing two tidal volumes, 15 patients (12.3%)
      developed pneumothorax. There was no significant difference in any pressure or
      volume between these patients and the rest of the population, including end
      inspiratory plateau pressure (P(plat)), driving pressure (P(plat)-PEEP),
      respiratory rate and compliance. Multiple trauma was more frequent among patients
      with pneumothorax (27%) than in those without (7%). Duration of mechanical
      ventilation tended to be longer with pneumothorax. In the literature review, the
      incidence of barotrauma varied between 0% and 49%, and correlated strongly with
      P(plat), with a high incidence above 35 cmH(2)O, and with compliance, with a high
      incidence below 30 ml/cmH(2)O. CONCLUSION: Clinical studies maintaining P(plat)
      lower than 35 cmH(2)O found no apparent relationship between ventilatory
      parameters and pneumothorax. Analysis of the literature suggests a correlation
      when patients receive mechanical ventilation with P(plat) levels exceeding 35
      cmH(2)O.

PMID- 11967594
TI  - What is the optimal duration of ventilation in the prone position in acute lung
      injury and acute respiratory distress syndrome?
AB  - OBJECTIVE: To evaluate the effects of prone ventilation on respiratory parameters
      and extravascular lung water (EVLW) in patients with acute lung injury (ALI) and
      acute respiratory distress syndrome (ARDS) in order to characterise the optimal
      duration of ventilation in the prone position. DESIGN: Prospective, observational
      study. SETTING: Nine-bed general intensive care unit. PATIENTS: Eleven patients
      with refractory hypoxaemia due to ALI/ARDS were prospectively investigated during
      12 consecutive episodes of prone ventilation. INTERVENTIONS: Ventilation in the
      prone position for 18 h. MEASUREMENTS AND MAIN RESULTS: Measurements were
      obtained supine and after 1, 2, 6, 12 and 18 h in the prone position and 1 h
      after returning supine. There was a progressive improvement in PaO(2)/fraction of
      inspired oxygen (FIO(2)) ratio which reached significance after 12 h [121 (81
      151) to 258 (187-329) torr; p<0.05]. EVLW index increased transiently at 1 h
      [14.2 (7.6-20.8) to 15.1 (9.0-20.2); p=0.05] and thereafter declined
      progressively and was significantly decreased at 18 h [12.1 (7.2-17.0); p=0.043].
      The shunt fraction showed an early fall [0.41 (0.40-0.42) to 0.31 (0.30-0.32) at
      1 h; p<0.001] preceding a subsequent progressive fall [0.22 (0.21-0.23) at 18 h;
      p<0.001]. CONCLUSIONS: Over the 18 h period studied there was progressive
      improvement in gas exchange, pulmonary shunt and EVLW. Although it is not
      possible to exclude that improvement over this period was unrelated to prone
      positioning, these findings suggests that ventilation in the prone position for
      more prolonged periods may be required for optimal improvement and warrants
      further study.

PMID- 11967595
TI  - Detection of brain death onset using the bispectral index in severely comatose
      patients.
AB  - OBJECTIVES: To evaluate the accuracy of bispectral index (BIS) monitoring for the
      diagnosis of brain death in severely comatose patients. DESIGN: A prospective
      study in an intensive care unit of a university hospital. POPULATION: Fifty-six
      severely comatose patients (Glasgow Coma Score < or = 5) admitted to the ICU
      mainly because of intracerebral hemorrhage, head injury, or postanoxic coma.
      METHODS: BIS was recorded continuously during the hospitalization in the ICU.
      Where necessary, clinical brain death was confirmed by EEG or cerebral
      angiography. MEASUREMENTS AND RESULTS: Twelve patients were already clinically
      brain dead at the time of admission, and their individual BIS values were 0. In
      each of these 12 patients brain death was thereafter confirmed by EEG or cerebral
      angiography. Forty-four patients were not clinically brain-dead at the time of
      admission, and their individual BIS values were between 20 and 79. Twenty-seven
      of these patients became brain-dead, and their individual BIS values dropped to 0
      in a few hours to a few days. In these 27 patients EEG or cerebral angiography
      was performed after the BIS value decreased to 0 and confirmed brain death in all
      cases. Seventeen patients who did not become brain dead during their
      hospitalization in the ICU had persistent electrocerebral activity on EEG, and
      their average BIS values remained above 35. CONCLUSION: BIS can be used in
      severely comatose patients as an assessment of brain death onset, enabling
      appropriate scheduling of either EEG or cerebral angiography to confirm brain
      death.

PMID- 11967596
TI  - Eradication of endotracheal tube biofilm by nebulised gentamicin.
AB  - OBJECTIVE: To compare the efficacy of gentamicin, nebulised via the endotracheal
      tube (ET), with that of parenteral cefotaxime or parenteral cefuroxime in
      preventing the formation of ET biofilm. SETTING: General intensive care units in
      two university teaching hospitals. DESIGN: The microbiology of ET biofilm from 36
      ICU patients eligible to receive antibiotic prophylaxis was examined. Peak and
      trough tracheal concentrations of gentamicin, cefotaxime or cefuroxime were
      measured in each patient group, on the 2nd day of intubation. PATIENTS: Twelve
      patients received gentamicin (80 mg) nebulised in 4 ml normal saline every 8 h,
      12 cefotaxime (1 g, 12 hourly) and 12 cefuroxime (750 mg, 8 hourly). Prophylaxis
      was continued for the duration of intubation. MEASUREMENTS AND RESULTS: Samples
      of tracheal secretions were taken on the 2nd day of ventilation for determination
      of antibiotic concentrations. Following extubation, ETs were examined for the
      presence of biofilm. Pathogens considered to be common aetiological agents for
      VAP included Staphylococcus aureus, enterococci, Enterobacteriaceae and
      pseudomonads. While microbial biofilm was found on all ETs from the cephalosporin
      group, microbial biofilm of these micro-organisms was found on 7 of the 12 ET
      tubes from patients receiving cefotaxime [ S. aureus (4), pseudomonads (1),
      Enterobacteriaceae (1), enterococcus (1)] and 8 of the 12 ET tubes from patients
      receiving cefuroxime [Enterobacteriaceae (6), P. aeruginosa (1) and enterococcus
      (1)]. While microbial biofilm was observed on five ETs from patients receiving
      nebulised gentamicin, none of these were from pathogens for ventilator-associated
      pneumonia (VAP). Tracheal concentrations of both cephalosporins were lower than
      those needed to inhibit the growth of pathogens recovered from ET tube biofilm.
      The median (and range) concentrations for cefotaxime were 0.90 (<0.23-1.31) mg/l
      and 0.28 (<0.23-0.58) mg/l for 2 h post-dose and trough samples, respectively.
      Two hours post-dose concentrations of cefuroxime (median and range) were 0.40
      (0.34-0.83) mg/l, with trough concentrations of 0.35 (<0.22-0.47) mg/l. Tracheal
      concentrations (median and range) of gentamicin measured 1 h post-nebulisation
      were 790 (352-->1250) mg/l and then, before the next dose, were 436 (250-1000)
      mg/l. CONCLUSION: Nebulised gentamicin attained high concentrations in the ET
      lumen and was more effective in preventing the formation of biofilm than either
      parenterally administered cephalosporin and therefore may be effective in
      preventing this complication of mechanical ventilation.

PMID- 11967597
TI  - Selective decontamination of subglottic area in mechanically ventilated patients
      with multiple trauma.
AB  - OBJECTIVE: To determine whether selective decontamination locally in the
      subglottic area (SDSA) reduces tracheal colonization and prevents ventilator
      associated pneumonia (VAP) in patients with multiple trauma. DESIGN AND SETTING:
      A prospective randomized, controlled, clinical study in a 14-bed general
      intensive care unit of a university hospital. PATIENTS: 79 consecutive multiple
      trauma patients admitted to the ICU who were expected to be mechanically
      ventilated for more than 5 days; 61 patients completed the protocol.
      INTERVENTION: Patients were randomly assigned to receive SDSA using a continuous
      infusion of a suspension containing three nonabsorbable antibiotics (polymyxin,
      tombramycin, and amphotericin B; n=30) or placebo ( n=31). MEASUREMENTS: The
      incidence of bronchial and gastric colonization and the number of cases of VAP
      were recorded. Gastric fluid and tracheal secretion cultures were obtained soon
      after intubation and thereafter every 4 days. Etiological diagnosis of VAP was
      based on samples taken by a specific protected double catheter set. RESULTS: VAP
      developed in 5 of 30 (16.6%) patients receiving SDSA and 16 of 31 (51.6%)
      patients receiving placebo. Negative bronchial secretion cultures were found in
      14 of 30 (46.6%) patients in the SDSA group and in only 3 of 31 (9.6%) patients
      in the control group. No patient with negative bronchial secretion culture
      developed VAP. No significant differences in outcome were found. CONCLUSIONS: The
      SDSA is an effective and safe type of chemoprophylaxis against tracheal
      colonization and can significantly reduce the incidence of VAP in mechanically
      ventilated patients with multiple trauma.

PMID- 11967598
TI  - Activity of antibacterial impregnated central venous catheters against Klebsiella
      pneumoniae.
AB  - OBJECTIVE: Antibiotically coated or impregnated catheters are effective in
      eliminating gram-positive bacteria from their surfaces. However, their activity
      against gram-negative bacteria is not well known. The aim of this study was to
      evaluate and compare the adherence, persistence and colonization of Klebsiella
      pneumoniae on catheter surfaces and also to assess bacteriostatic and
      bactericidal levels. DESIGN: Randomized, controlled, laboratory study. SETTING:
      University surgical microbiology laboratory. SUBJECTIVE: Silver sulfadiazine
      chlorhexidine impregnated (SSC), minocycline and rifampin bonded (M+R), silver,
      platinum and carbon incorporated (SP+C) and non-antiseptic central venous
      catheter segments. INTERVENTIONS: Catheter segments were immersed in 1 ml of
      phosphate buffered saline (0.01 mol/l) with 0.25% dextrose (PBSD) and incubated
      at 37 degrees C. The PBSD was replaced daily. Effluents were frozen at -70
      degrees C for subsequent determination of bacteriostatic and bactericidal
      activity. On days 1,3,7,14 and 21 after initial immersion, 1 ml standardized
      inoculum of Klebsiella pneumoniae was added to 90 tubes for a period of 30 min.
      The inoculum was then replaced with PBSD. One third of the samples were
      immediately sonicated and plated for the determination of bacterial adherence.
      The remaining segments were incubated for 4 and 24 h, followed by the same
      procedure to determine bacterial persistence and colonization with time. All
      plates were read after 24 h of incubation. MEASUREMENTS AND RESULTS: There was a
      significant reduction in initial bacterial adherence for SP+C catheters on all
      days ( p<0.05). SSC catheters prevented initial bacterial adherence for the first
      7 days only ( p<0.05). SSC and SP+C catheters prevented bacterial persistence and
      further colonization on all days. However M+R catheters prevented bacterial
      colonization for 3 days only. Effluent studies indicated that the impregnated
      agents in catheter SSC were bactericidal compared to catheter M+R, which were
      bacteriostatic to K. pneumoniae. No antibacterial activity was detected in the
      effluents from catheter SP+C. CONCLUSIONS: SSC and SP+C catheters are effective
      in eliminating K. pneumoniae from their surfaces for at least 21 days. M+R
      catheters are less effective in eliminating bacterial adherence and colonization
      may be due to their bacteriostatic property.

PMID- 11967599
TI  - Evaluation of ventilators used during transport of ICU patients -- a bench study.
AB  - OBJECTIVES: To evaluate portable ventilators. DESIGN AND SETTINGS: Bench study.
      MATERIALS AND METHODS: Five portable ventilators used for transporting ICU
      patients [Osiris 1, (ventilator a), Osiris 2, (ventilator b), Oxylog 1000,
      (ventilator c), Oxylog 2000, (ventilator d), AXR1a, (ventilator e)] and three ICU
      ventilators which can be used for this purpose [Horus, (ventilator f), T-Bird,
      (ventilator g), and SV 300, (ventilator h)] were compared using a test lung
      regarding: 1) their capability to maintain set tidal volumes (V(T)) of 300 ml,
      500 ml, and 800 ml under a normal condition A [resistance (R) 5 cmH(2)O/l/s and
      compliance (C) 100 ml/cmH(2)0] and two abnormal conditions B (R 20-C 30) and C (R
      50-C 100); 2) trapped volume (expired V(T)relative to inspired V(T)at 0.7 s, 1 s,
      and 1.4 s), an estimate of the expiratory resistance of both circuit and valve;
      and 3) the triggering system assessed from the measurements of Delta t, Delta P
      for two inspiratory efforts at a PEEP of 0 cmH(2)0 and 5 cmH(2)0 in ventilators
      b, d, f, g, and h. Flow and airway pressure were measured with an independent
      physiologic recording system. RESULTS: 1) V(T). For ventilators a-h, the mean+/
      SD changes of a set V(T)of 300 ml were -2.6+/-0.2%, -9.7+/-0.2%, 0+/-0%, -6.1+/
      0.2%, 1.0+/-0.3%, -2.1+/-1.7%, 0.3+/-0%, and -1.3+/-0.1% ( P<0.001),
      respectively, during condition B relative to A. Similar results were obtained for
      a V(T)of 500 ml and 800 ml and during condition C relative to A; 2) Trapped
      volume. For ventilators a-h, trapped volume averaged 1+/-1%, 20+/-0%, 30+/-0.4%,
      20+/-1%, 1+/-0%, 19+/-0%, 15+/-0%, and 14+/-0% at 0.7 s ( P <0.001) and 0.6+/-0%,
      5+/-0%, 0.5+/-0%, 0+/-0%%, 0+/-0%, 0.6+/-0%, 0+/-0%, and 0+/-0% at 1.4 s ( P=NS);
      and 3) the triggering system of Oxylog 2000 was poor whereas it was of good
      quality for Horus, T-Bird, SV 300, and Osiris 2. CONCLUSIONS: The small portable
      ventilators presently investigated varied between each other and were less
      accurate than ICU ventilators.

PMID- 11967600
TI  - Critical incidents related to invasive mechanical ventilation in the ICU:
      preliminary descriptive study.
AB  - OBJECTIVES: To establish a preliminary list of critical incidents (CIs)
      associated with mechanical ventilation and to describe a CI reporting method.
      DESIGN: A list of CIs was established based on a consensus among ICU caregivers.
      The list was compared to CIs collected prospectively during a predefined study
      period. SETTING: The clinical observations were conducted in two intensive care
      units. PATIENTS: All patients receiving mechanical ventilation were included.
      MEASUREMENTS AND RESULTS: The list of CIs included death and 62 other CI types
      categorized as immediately life-threatening, secondarily life-threatening, or non
      life-threatening. The observational study identified 527 CIs in 137 patients.
      Virtually all non-life-threatening CIs were ascribed to failure to comply with
      safety rules or to equipment failure and 40% of life-threatening CIs to the
      course of the disease or to patient-related factors. The match between CI types
      on the list and CI types observed in the ICUs was excellent. CONCLUSIONS: Use of
      our reporting method to create a CI database in a multicenter study including
      ICUs with varying recruitment patterns may help to identify markers suitable for
      routine continuous use as part of a quality-assurance program.

PMID- 11967601
TI  - H(2) antagonist-induced thrombocytopenia: is this a real phenomenon?
AB  - Critically ill patients routinely receive H(2) antagonists for stress ulcer
      prophylaxis while at risk for gastrointestinal bleeding. In these patients it is
      often difficult to assess accurately the cause of adverse effects such as
      thrombocytopenia. We evaluate the literature to better define thrombocytopenia
      related to H(2) antagonist administration and discuss mechanism, potential as a
      risk factor and case reports describing the severity and duration of
      thrombocytopenia.

PMID- 11967602
TI  - Does coagulation differ between elderly and younger patients undergoing cardiac
      surgery?
AB  - OBJECTIVE: Multiple improvements allow cardiac surgery in an increasingly older
      population. It is still unclear whether perioperative hemostasis differs between
      elderly and younger patients. DESIGN: Prospective, observational study. SETTING:
      Single institutional study at an urban, university-affiliated hospital. PATIENTS:
      Twenty-one consecutive patients aged over 80 years and 21 consecutive patients
      aged under 60 years undergoing first-time elective aortocoronary bypass grafting.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Modified thromboelastography (TEG)
      using different activators [intrinsic TEG (InTEG); extrinsic TEG (ExTEG);
      fibrinogen TEG (fibTEG)] was carried out to measure coagulation time [CT =
      reaction time (r)], clot formation time [CFT = coagulation time (k)], and maximum
      clot firmness [MCF = maximal amplitude (MA)]. Measurements were performed before
      surgery, at the end and 5 h after surgery on the intensive care unit (ICU), and
      on the morning of the 1st postoperative day (POD). Blood loss was slightly higher
      in the elderly than in the younger patients. Most TEG data were already
      significantly different between elderly and younger patients at baseline,
      indicating altered coagulation in the elderly prior to surgery
      (hypocoagulability). After surgery and on the ICU, elderly patients showed
      similar alterations in TEG to those of the younger patients (e.g. InTEG-CT: from
      183+/-21 to 239+/-28 s versus from 146+/-15 to 186+/-26 s). On the 1st POD, most
      TEG data had returned almost to baseline values, however, they were still
      different between elderly and younger patients. CONCLUSIONS: Elderly cardiac
      surgery patients already showed moderately altered coagulation prior to surgery.
      Thus elderly patients may be at risk of developing postoperative alterations in
      hemostasis on the ICU. The exact reasons for the impaired coagulation in the
      elderly remains to be determined.

PMID- 11967603
TI  - Association between early detection of soluble TNF-receptors and mortality in
      burn patients.
AB  - OBJECTIVES: To describe early sequential profiling of circulating levels of tumor
      necrosis factor alpha (TNF-alpha), TNF-1 and TNF-2 soluble receptors (sTNFR1 and
      sTNFR2), and of endothelin (ET-1) in patients with severe burn injury, and its
      association with mortality. DESIGN: Prospective study. SETTING: Intensive Care
      Burn Unit at a community hospital. PATIENTS: Twenty patients with total burn
      surface area (TBSA)> or = 30%. INTERVENTIONS: None. MEASUREMENTS AND RESULTS:
      Patients were enrolled within 6 h from the injury. Blood samples were drawn at
      zero, 6, 12, and 24 h for sequential ELISA measurement of plasma marker levels.
      Data are expressed as mean+/-SD. Age, TBSA, and inhalation injury were not
      significantly different between survivors ( n=9; 30+/-13 years, TBSA 40+/-12%)
      and nonsurvivors ( n=11, 38+/-15 years, TBSA 56+/-20%). sTNFR1 levels were
      increased in nonsurvivors (2937+/-1676 pg/ml; 4548+/-1436 pg/ml) as compared to
      survivors (1313+/-561 pg/ml; 2561+/-804 pg/ml) at 6 h and 24 h, respectively (
      P=0.01 and 0.002). sTNFR2 levels were significantly increased in nonsurvivors
      (4617+/-1,876 pg/ml vs 2611+/-1,326 pg/ml) only at 6 h ( P=0.015). TNF-alpha and
      ET-1 levels were not different between nonsurvivors and survivors. After
      adjustment for TBSA, sTNFR1 and sTNFR2 remained significantly higher in
      nonsurvivors. CONCLUSION: Early and progressive increase in sTNFR1 and sTNFR2
      levels is associated with higher risk for poor outcome in severely burned
      patients.

PMID- 11967604
TI  - Customized prediction models based on APACHE II and SAPS II scores in patients
      with prolonged length of stay in the ICU.
AB  - OBJECTIVE: To study customized APACHE II and SAPS II models in predicting
      hospital death in patients with a prolonged length of stay in the ICU. DESIGN:
      Prospectively collected database. SETTING: Thirteen ICUs with 5-10 beds in
      Finnish secondary referral hospitals. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: The database was collected between 1994 and 1999 and included 23,953 ICU
      admissions. In order to customize the original APACHE II and SAPS II models and
      to validate the models, the database was randomly divided into customization data
      ( n=12,064) and into validation data ( n=11,889). Logistic regression analysis
      was used for customization. As the length of the ICU stay was prolonged, the
      calibration and discrimination of both customized models worsened gradually in
      the validation data. Patients whose ICU stay lasted 7 days or longer (1,312
      patients) consumed more than one half of all ICU days and TISS-points. Among
      these patients, goodness-of-fit statistics was 221.5 and 306.3 ( P<0.0001 for
      both) and the areas under ROC curve 0.65 and 0.62 for the customized APACHE and
      SAPS models, respectively. The models underestimated the risk of death in the low
      range and overestimated it in the high range of predicted mortality. On the other
      hand, both models discriminated well between survivors and non-survivors if the
      ICU stay was 2 days or less. CONCLUSIONS: Despite customization, the predictive
      models may not support clinical decision-making in those patients who require a
      high share of resources. More relevant instruments are needed for the prediction
      of outcome of patient groups who consume the major part of ICU resources.

PMID- 11967605
TI  - Mechanical ventilation alters the immune response in children without lung
      pathology.
AB  - OBJECTIVE: This study was undertaken to examine the hypothesis that mechanical
      ventilation in association with anesthesia would alter the cytokine profile in
      infants without preexisting lung pathology. DESIGN AND SETTING: Prospective
      observational study in pediatric intensive care unit in a university hospital.
      PATIENTS: Twelve infants who were subjected to an uncomplicated diagnostic
      cardiac catheterization procedure were studied. All subjects were ventilated with
      a volume control mode, 0.3 FIO(2), 4 cmH(2)O PEEP, and 10 ml/kg tidal volume.
      Volatile (servoflurane) anesthetics were given. MEASUREMENTS AND RESULTS:
      Tracheal aspirates and blood samples were obtained before and after 2 h of
      mechanical ventilation. In tracheal aspirates and in supernatants of stimulated
      whole-blood cultures cytokine concentrations were measured. In the tracheal
      aspirates the immune balance was characterized by a proinflammatory response
      pattern, with a significant increase in TNF-alpha and IL-6 concentrations;
      concentrations of anti-inflammatory mediators remained very low. The functional
      capacity of peripheral blood leukocytes to produce INF-gamma, TNF-alpha, and IL-6
      in vitro was significantly decreased. This was accompanied by a significant
      decrease in the killing activity of natural killer cells. CONCLUSIONS: Two hours
      of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is
      associated with remarkable changes in the immune response in infants without
      preexisting lung pathology undergoing cardiac catheterization. In the lungs the
      immune balance favors a proinflammatory response pattern without detectable
      concentrations of anti-inflammatory mediators. The Th1 immune response by
      peripheral blood leukocytes was decreased. The observed change in Th1/Th2 balance
      in favor of Th2 cytokine activity may be a systemic adaptation to the
      proinflammatory milieu in the lung.

PMID- 11967606
TI  - Ciprofloxacin pharmacokinetic profiles in paediatric sepsis: how much
      ciprofloxacin is enough?
AB  - OBJECTIVE: To determine the pharmacokinetic profile of ciprofloxacin 20 mg/kg per
      day (10 mg/kg administered intravenously 12 hourly) in paediatric patients with
      severe sepsis. DESIGN: Open and prospective. SETTING: Tertiary referral multi
      disciplinary ICU. PATIENTS: Twenty patients (two groups - group A: 3 months-1
      year; group B 1-5 years). INTERVENTIONS: Timed blood samples were taken for
      pharmacokinetics after the first dose (D(0)), as well as day 2 (D(2)) and then
      between days 6-8. MEASUREMENTS AND RESULTS: Ciprofloxacin serum levels were
      measured by high performance liquid chromatography. Demographic and clinical data
      and all adverse events were noted. Standard pharmacokinetic variables were
      calculated by non-compartmental methods. Peak concentrations (C(max)) for group A
      were D(0) 6.1+/-1.2 mg/l, D(2) 9.0+/-1.8 mg/l and D(7) 5.8+/-1.3 mg/l and, for
      group B, 7.4+/-1.3 mg/l, 7.8+/-1.6 mg/l and 6.4+/-1.3 mg/l, respectively, for the
      study periods. Concentration 12 h after the start of infusion (C(min)) for all
      periods were 0.2 mg/l or less. Areas under the curve (AUC, 12 h) were group A:
      15.6+/-1.3, 19.2+/-1.63 and 14.1+/-1.4 mg/h per l, and group B: 15.9+/-1.3,
      18.0+/-1.7 and 13.2+/-1.26 mg/h per l. One patient presenting with seizures,
      initially controlled, had another convulsion and a further patient developed
      seizures whilst on ciprofloxacin. C(max) in these patients were higher than the
      average C(max). The convulsions of both patients were easily controlled. No other
      drug-related serious adverse events occurred. No arthropathy was noted. Three
      patients died of their underlying disease. CONCLUSIONS: There was no accumulation
      of drug even after 7 days of administration. Our C(max) and AUC were lower than
      that achieved in a similar adult pharmacokinetic study. To achieve end points of
      area under the inhibitory curve (AUIC) of 100-150 mg/h per l, 10 mg/kg
      ciprofloxacin eight hourly would be required for some resistant ICU organisms.

PMID- 11967607
TI  - Transcatheter closure of a patent arterial duct in a patient on veno-arterial
      extracorporeal membrane oxygenation.
AB  - The presence of a patent arterial duct may complicate the course of the patient
      on veno-arterial extracorporeal membrane oxygenation (ECMO). While surgical
      ligation has been traditionally used as a definitive treatment for this problem,
      transcatheter closure may have advantages. This is the first report of
      transcatheter occlusion of a patent arterial duct in an infant on ECMO support.

PMID- 11967608
TI  - Tracheal gas insufflation during late exhalation efficiently reduces PaCO(2) in
      experimental acute lung injury.
AB  - OBJECTIVE: Tracheal gas insufflation (TGI) reduces PaCO(2) by flushing the
      tracheal and mechanical deadspace, and may have its maximum benefit when TGI gas
      is unopposed by significant expiratory gas flow. Thus, limiting TGI to the late
      expiratory period may diminish tracheal exposure to TGI gas while preserving the
      efficacy of TGI. This study examined the gas exchange consequences of such late
      expiratory TGI. DESIGN AND SETTING: Randomized controlled trial, animal study.
      MATERIALS: Eleven pigs. INTERVENTIONS: After stable lung injury was established
      using oleic acid 11 pigs were ventilated using a standardized lung protective
      strategy. Phasic expiratory TGI was applied for 30 min stages during the last
      20%, 40%, 60%, and 100% of expiration in random sequence. PaCO(2) was
      continuously measured via an indwelling blood gas analysis system. MEASUREMENTS
      AND RESULTS: PaCO(2) at baseline was 86.1+/-4.7 mmHg, and decreased progressively
      with increasing TGI duration of 20%, 40%, and 60%, but not 100%, of expiration
      (PaCO(2)=75.7+/-5.2, 68.8+/-3.6, 65.1+/-5.3 and 65.2+/-5.2 mmHg, respectively).
      For all stages the reduction in PaCO(2) relative to baseline was significant.
      Trends of increasing PaO(2) and airway pressure with increasing TGI duration were
      noted and most likely associated with a TGI-induced increase in lung volume.
      CONCLUSIONS: Under these conditions confining TGI to the final 60% of expiration
      achieved effective PaCO(2) reduction, not significantly different from
      panexpiratory TGI, while limiting exposure of the trachea to TGI gas, and
      reducing the potential for TGI-induced hyperinflation. These findings suggest
      that TGI is most effectively applied in a phasic manner in late expiration, with
      its duration titrated to effect.

PMID- 11967609
TI  - Comparison of different methods for measuring intra-abdominal pressure.
AB  - OBJECTIVE: Intra-abdominal pressure (IAP) can be measured in different ways but
      is usually measured indirectly via the urinary bladder. The aim of the study was
      to: 1) compare urinary bladder pressure, femoral vein pressure, and inferior
      caval vein pressure with IAP at different levels of IAP; and 2) try to find an
      optimal amount of fluid to be instilled into the urinary bladder before
      measurement of the bladder pressure, and to compare changes in blood flow in the
      femoral vein with that in the caval vein at different pressure levels. DESIGN:
      Experimental study. SETTING: Animal research laboratory. SUBJECTS: Eight domestic
      swine of both sexes, weighing 30.6+/-2.9 kg (mean+/-SD). INTERVENTIONS: Catheters
      connected to pressure transducers were placed into the urinary bladder, the
      inferior caval vein, the femoral vein, and the superior caval vein. Transit time
      flow probes were placed around the inferior caval vein and the femoral vein.
      After a stabilizing period, the abdominal pressure was increased stepwise by
      instillation of Ringer's solution into the abdomen and then decreased.
      Thereafter, we instilled fluid into the bladder at an IAP of 8 mmHg and at 20
      mmHg and measured the amount of fluid needed to elevate the intra-vesical
      pressure by 2 mmHg. RESULTS: The pressures recorded in the urinary bladder, the
      inferior caval vein, and the femoral vein reflected the pressure in the abdominal
      cavity very well. The fluid volume needed to increase the bladder pressure by 2
      mmHg was significantly lower at 20 mmHg IAP than at 8 mmHg. Blood flow in the
      femoral vein and the inferior caval vein showed a similar pattern and decreased
      when the intra-abdominal pressure increased. CONCLUSIONS: In our porcine model,
      and increasing the IAP by means of instillation of Ringer's solution, a reliable
      estimation of the IAP was obtained by measuring the pressure in the urinary
      bladder, the femoral vein or the inferior caval vein. The IAP estimated
      indirectly as the urinary bladder pressure is affected by the amount of fluid in
      the bladder, which should not exceed 10-15 ml. The decrease in femoral vein blood
      flow reflects the changes in inferior caval vein flow during increased IAP.

PMID- 11967610
TI  - Inappropriate ventilator triggering caused by an in-line suction catheter.
AB  - OBJECTIVE: To examine the phenomenon of inappropriate triggering caused by an in
      line suction catheter. DESIGN: We used a test lung to assess inappropriate
      triggering in four ventilators with both pressure and flow triggering. RESULTS:
      With pressure triggering, inappropriate triggering occurred only in the presence
      of PEEP. However, with flow triggering, inappropriate triggering occurred both
      with and without PEEP. Inappropriate triggering did not occur in a model of
      severe airflow obstruction. CONCLUSION: In-line suction catheters may lead to
      inappropriate triggering and potentially dangerous increases in delivered
      ventilation.

PMID- 11967611
TI  - Piperacillin-induced magnesium and potassium loss in intensive care unit
      patients.
AB  - OBJECTIVE: Broad spectrum penicillins such as piperacillin are used extensively
      in the intensive care unit (ICU) because of their wide bacterial spectrum and low
      level of toxicity. Although some cases of interstitial nephritis induced by
      piperacillin have been reported, this problem is thought to be rare. However, in
      view of the large number of other risk factors for renal disorders that are
      frequently present in ICU patients, we speculated that ICU patients might be more
      at risk for renal side effects. We therefore decided to measure serum electrolyte
      levels in patients before and after piperacillin administration. DESIGN:
      Prospective observational study. SETTING: University teaching hospital. PATIENTS
      AND PARTICIPANTS: Forty-three consecutive patients with normal renal function
      treated with piperacillin; 40 patients treated with other antibiotics. RESULTS:
      Serum levels of magnesium (Mg), potassium (K) and, to a lesser degree, calcium
      (Ca) decreased significantly in patients treated with piperacillin, but not in
      patients treated with other antibiotics ( p<0.01). This decrease was especially
      pronounced in a subgroup of patients concurrently treated with furosemide.
      CONCLUSIONS: We conclude that treatment with piperacillin may cause or aggravate
      electrolyte disorders and tubular dysfunction in ICU patients even when serum
      creatinine levels remain normal.

PMID- 11967612
TI  - Internal herniation and strangulation of the ileus through a post-traumatic
      defect of the mesentery in an intensive care unit patient. A case report.

PMID- 11967613
TI  - Full recovery after 45 min accidental submersion.

PMID- 11967617
TI  - A meta-analysis for neurobehavioural results due to occupational mercury
      exposure.
AB  - A meta-analysis for neurobehavioural test results of subjects occupationally
      exposed to mercury was carried out in order to find general tendencies and
      express possible deficits numerically. Out of 44 studies investigating
      neurobehavioural functions of occupationally exposed individuals, 12 studies
      provided the data required and were included in the analysis. In all, 14
      neuropsychological tests with 20 different tasks were analysed. The results
      related to 686 exposed and 579 control subjects. Nine significant performance
      effects were shown for mean urinary concentrations between 18 and 34 microg Hg/g
      creatinine. The effects sizes (D(W+)) referred to attention (D(W+)=-0.40 and 
      0.46), memory (D(W+)=-0.38 and -0.40), construction (D(W+)=-0.20) and motor
      performance (D(W+)=-0.24, -0.40, -0.44 and -0.47). Additionally there was
      evidence for a dose-response relationship of effect sizes, if all test results
      were taken into account. Whether the effect sizes could be subject to
      overestimation was discussed, but there were no reasons for such an assumption.
      The results can be used as suggestions for new discussions about threshold limit
      values.

PMID- 11967618
TI  - A summary of two meta-analyses on neurobehavioural effects due to occupational
      lead exposure.
AB  - The conclusions from published results about neurotoxic effects of inorganic lead
      exposures <700 microg lead/l blood are contradictory at present. Effects measured
      by neurobehavioural methods are evaluated differently as far as recommendations
      for a Biological Exposure Index (BEI) of occupational lead exposure are
      concerned. Arguments against the German BEI of 400 microg/l were put forward in
      new publications, and discussion of the issues is the aim of this article. It
      summarizes two different meta-analytical reviews on neurobehavioural effects in
      order to show the main tendencies of 24 selected publications on the matter.
      Calculations on effect sizes are compiled for 12 tests analysed in two meta
      analyses and of ten tests analysed in one of the meta-analyses. The survey of six
      tests of learning and memory gives hints on impairments measured with two tests,
      covering Logical Memory and Visual Reproduction. The survey of seven tests of
      attention and visuospatial information processing describes impairments in four
      tests, namely Simple Reaction, Attention Test d2, Block Design, and Picture
      Completion. The survey of four tests for psychomotor functions shows impairments
      for three tests, namely Santa Ana, Grooved Pegboard, and Eye-hand Coordination.
      These test results provide evidence for subtle deficits being associated with
      average blood lead levels between 370 and 520 microg/l. In evaluating the
      adversity of such effects it is concluded that the results of both meta
      analytical reviews support the recommendation for the German BEI.

PMID- 11967619
TI  - Lung expression of cytochrome P450 1A1 as a possible biomarker of exposure to
      diesel exhaust particles.
AB  - Polycyclic aromatic hydrocarbons (PAH) and reactive oxygen species (ROS) derived
      from diesel exhaust particles (DEP) are implicated in the pathophysiology of
      respiratory diseases. Cytochrome P450 (Cyp) 1A1 can be induced by several kinds
      of PAH and produce ROS. We determined whether acute inhalation exposure to DEP
      induced the expression of Cyp 1A1 in murine lung. Intratracheal instillation of
      DEP dose-dependently increased the lung expression of Cyp 1A1 at the levels of
      both mRNA and protein, whereas DEP decreased expression in the lung of aryl
      hydrocarbon receptors in a dose-dependent manner. In contrast, charcoal particles
      as the control did not affect the expression of these molecules. These results
      suggest that the lung expression of Cyp 1A1 can be a biomarker of acute
      inhalation exposure to DEP and may be implicated in an accelerated production of
      ROS and the subsequent aggravation of lung injury.

PMID- 11967620
TI  - Increased oxidative stress in subjects exposed to carbon disulfide (CS2)--an
      occupational coronary risk factor.
AB  - There is considerable epidemiological evidence that workers exposed to carbon
      disulfide (CS2) develop premature atherosclerosis leading to increased rates of
      coronary heart disease (CHD), but mechanisms underlying this association remain
      obscure. The present study documents that occupational exposure to CS2 modifies
      the oxidative status of plasma, which is a major determinant of the
      susceptibility to atherosclerosis. Concentrations of thiobarbituric reactive
      substances (TBARS), which reflect lipid peroxidation processes in plasma, were
      determined in 29 men who were exposed to CS2 for more than 20 years, in 24
      patients with peripheral atherosclerosis, and in 30 unexposed, healthy control
      subjects. TBARS concentrations were significantly increased both in CS2-exposed
      subjects and in patients with peripheral atherosclerosis. Subjects in both groups
      presented also with decreased levels of plasma alpha-tocopherol, a major plasma
      antioxidant. In addition, decreased activities of two enzymatic antioxidants,
      glutathion peroxidase and catalase, were noted both in CS2-exposed subjects and
      patients with peripheral atherosclerosis. Finally, LDL isolated from both groups
      showed increased susceptibility to transition metal-induced oxidation in vitro.
      It is concluded, that occupational exposure to CS2 produces oxidative stress in
      plasma. This may favor the development of atherosclerosis and increase the
      incidence of CHD in workers exposed to CS2.

PMID- 11967621
TI  - Protective effect of melatonin against nodularin-induced oxidative stress.
AB  - Nodularin is a hepatotoxin from a cyanobacterium, Nodularia spumigena, that
      inhibits protein phosphatases 1 and 2 and posseses tumor-promoting activity. The
      aim of this paper was to examine whether nodularin is able to induce oxidative
      stress in mouse liver tissue and whether melatonin (protective compound against
      oxidative damage) could supress the activity of nodularin. We studied the effect
      of nodularin (1, 5, and 10 microg/kg body weight) and melatonin (5, 10, and 15
      mg/kg body weight) administration on the activity of superoxide dismutase (SOD),
      catalase (CAT) and glutathione peroxidase (GSH-Px) in mouse liver.
      Intraperitoneal treatment of mice with nodularin per 7 days decreased the
      activities of all estimated enzymes in a dose-dependent manner. Intraperitoneal
      treatment of animals with melatonin per 7 days increased the activities of SOD,
      CAT, and GSH-Px and this effect was concentration-dependent. Co-treatment
      (nodularin 5 microg/kg body weight + melatonin 5, 10, and 15 mg/kg body weight
      per 7 days) and post-treatment with melatonin (nodularin 5 microg/kg body weight
      per 7 days + melatonin 5, 10, and 15 mg/kg body weight per next 7 days) increased
      the activities of SOD, CAT, and GSH-Px in comparison to the nodularin group. No
      significant differences from the nodularin group were noted in the group after
      pre-treatment with melatonin. In conclusion, these findings suggest that
      oxidative damage may be involved in the toxicity of nodularin. Moreover, co
      treatment and post-treatment with 10 and 15 mg/kg body weight of melatonin may
      protect against nodularin-induced oxidative stress. There was no protective
      effect of pre-treatment with melatonin.

PMID- 11967622
TI  - Effect of 3,4-methylenedioxymethamphetamine ("ecstasy") on body temperature and
      liver antioxidant status in mice: influence of ambient temperature.
AB  - The consumption of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is known to
      cause severe hyperthermia and liver damage in humans. The thermogenic response
      induced by MDMA is complex and partially determined by the prevailing ambient
      temperature (AT). This is of extreme importance since ecstasy is often consumed
      at "rave" parties, where dancing takes place in a warm environment, which may
      exacerbate the effect of MDMA on thermoregulation. In view of the fact that
      hyperthermia is a well-known pro-oxidant aggressive condition, its potential role
      in ecstasy-induced hepatocellular toxicity should be further studied. Thus, the
      present study was performed in order to evaluate the influence of AT on the
      effects of single administration of MDMA on body temperature and liver toxicity
      in Charles River mice. Animals were given an acute intraperitoneal dose of MDMA
      (5, 10 or 20 mg/kg) and placed in AT of 20+/-2 degrees C or 30+/-2 degrees C for
      24 h. Body temperature was measured during the study using implanted transponders
      and a temperature probe reading device. Plasma and liver samples were used for
      biochemical analysis. Liver sections were also taken for histological
      examination. The parameters evaluated were (1) plasma levels of transaminases and
      alkaline phosphatase, (2) hepatic glutathione (GSH), (3) hepatic lipid
      peroxidation, (4) activity of hepatic antioxidant enzymes (catalase, glutathione
      peroxidase, glutathione reductase, glutathione- S-transferase, copper/zinc
      superoxide dismutase and manganese superoxide dismutase), and (5) liver
      histology. The hyperthermic response elicited by MDMA was clearly dose-related
      and potentiated by high AT. Administration of MDMA produced some evidence of
      oxidative stress, expressed as GSH depletion at both ATs studied, as well as by
      lipid peroxidation and decreased catalase activity at high AT. High AT, by
      itself, decreased glutathione peroxidase activity. Histological examination of
      the liver revealed abnormalities of a dose- and AT-dependent nature. These
      changes included vacuolation of the hepatocytes, presence of blood clots and loss
      of typical hepatic cord organisation. The results obtained in the present study
      suggest that oxidative stress plays a part in the first stage of MDMA-induced
      liver damage and that liver antioxidant status is aggravated by increased AT.
      Thus, these findings are in accordance with the hypothesis that high AT may
      potentiate ecstasy-induced hepatotoxicity by increasing body hyperthermia.

PMID- 11967623
TI  - Adamantyl tenocyclidines--adjuvant therapy in poisoning with organophosphorus
      compounds and carbamates.
AB  - The objective of this study was to evaluate the efficacy of thienyl phencyclidine
      (tenocyclidine, TCP) and its newly synthesized adamantyl derivatives containing
      piperidine (TAPIP), pyrolidine (TAPIR) and morpholine (TAMORF) groups, which were
      tested with or without standard therapy in mice poisoned with organophosphates
      (OPs) and carbamates. These compounds with potential activity at the N-methyl- D
      aspartate and muscarinic receptors showed low acute toxicity, having LD50 values
      varying from 106.00 mg/kg (TCP) to >504.00 mg/kg body weight (TAMORF). TCP and
      its adamantyl derivatives were administered intraperitoneally (2.5 mg/kg body
      weight) together with atropine (10.0 mg/kg body weight) and with or without 1/4
      LD50 of the oxime HI-6. Each compound administered with atropine had a
      therapeutic effect against poisoning with carbamates propoxur, aldicarb and Ro 02
      0683 (protective ratio of tenocyclidines was from 3.99 LD50 of aldicarb to >16.00
      LD50 for propoxur). However, the efficacy of those compounds in combination with
      atropine was lower against poisoning with the OP insecticide dichlorvos (DDVP)
      and chemical warfare agents soman and tabun. In soman-poisoned mice, the best
      therapeutic effects were obtained with the combination of HI-6 plus atropine and
      test compounds, with protective ratios being from 5.40 to 7.12 LD50 of soman. The
      results suggest that TCP and adamantyl tenocyclidines could be used in
      combination with atropine as antidotes in carbamate poisoning and as adjuvant
      therapy to HI-6 and atropine in soman poisoning.

PMID- 11967624
TI  - Susceptibility factors and DNA adducts in peripheral blood mononuclear cells of
      aluminium smelter workers exposed to polycyclic aromatic hydrocarbons.
AB  - Formation of DNA adducts as a result of exposure to polycyclic aromatic
      hydrocarbons (PAH) was studied in 98 potroom workers from an aluminium smelting
      plant and in 55 blue-collar workers without occupational PAH exposure. DNA from
      peripheral blood mononuclear cells (PBMC) was used for quantitation of individual
      PAH-DNA adducts by 32P-postlabelling/high performance liquid chromatography
      (HPLC) analysis. Four individual DNA adducts (denoted A, B, C and D) were
      quantified in 141 of a total of 153 subjects. Genetic polymorphisms for
      cytochrome P-4501A1 ( CYP1A1), microsomal epoxide hydrolase, N-acetyltransferase
      2, glutathione transferases M1, P1 and T1 ( GSTM1, GSTP1 and GSTT1, respectively)
      and NAD(P)H: quinone oxidoreductase 1 (NQO1) were analysed. For 52 subjects,
      analysis of mRNA inducibility of CYP1A1 was performed. No statistically
      significant differences in the levels of total or individual DNA adducts A, C and
      D were found between potroom workers and control subjects. All potroom workers
      and the subgroup of potroom workers who reported to never/sometimes use personal
      respiratory protection ( n=72) were found to have a significantly higher
      likelihood of having high levels of adduct B than control subjects [odds ratio
      (OR) =3.4 with 95% confidence interval (CI) of 1.3-9.2, and OR=4.2 with 95% CI
      1.6-11.5, respectively]. In the subgroup, levels of adducts A and B were found to
      be significantly higher among workers with employment time of less than 6 months
      ( n=5). Also, the levels of the individual DNA adducts were to some extent
      modified by genetic polymorphisms in CYP1A1, GSTM1, GSTP1 and NQO1 and by CYP1A1
      inducibility. In conclusion, levels of adduct B, identified by 32P
      postlabelling/HPLC methodology as an indicator of PAH exposure in aluminium
      production, were modified by the use of respiratory protection, length of
      employment and genetic polymorphisms.

PMID- 11967625
TI  - Behavioral pharmacology of buprenorphine, with a focus on preclinical models of
      reward and addiction.
AB  - RATIONALE: Buprenorphine is a potent mu-receptor partial agonist and is widely
      used as an analgesic drug. It is also increasingly considered to be an
      alternative to methadone in the maintenance and eventual detoxification of heroin
      addicts, and also in the treatment of cocaine addiction. So far, buprenorphine
      has been available as a sublingual tablet and as a solution for IV injection.
      Recently, a new transdermal formulation of buprenorphine in slow-release matrix
      patches has been introduced (Transtec) for the treatment of intermediate to
      severe pain. OBJECTIVES: The aim of this paper is to review, from a preclinical
      perspective, the current status of what is known about the behavioral
      pharmacology of buprenorphine, with a particular emphasis on the issues of
      reward, addiction, and dependence. It will also point to open questions that
      should be addressed in the future to improve our understanding of the effects and
      the mechanisms of action of this drug. RESULTS AND CONCLUSIONS: Since
      buprenorphine is a potent opioid drug, the issue of addiction and dependence in
      this context is an important one. Although there are still some gaps in the
      behavioral pharmacological characterization of buprenorphine, the general
      conclusion that can be drawn from the reviewed literature is that despite the
      high affinity of buprenorphine for the mu receptor it appears to be a remarkably
      safe drug, with a benign overall side effect profile and low addictive and
      dependence-inducing potential. This favorable side effect profile appears to be
      due, to a large extent, to the partial agonistic properties of the drug, in
      combination with its particular receptor kinetics (i.e. very slow dissociation
      from the mu receptor after binding).

PMID- 11967626
TI  - Effects of a newly synthesized kappa-opioid receptor agonist, TRK-820, on the
      discriminative stimulus and rewarding effects of cocaine in rats.
AB  - RATIONALE: We previously demonstrated that the prototypical kappa-opioid receptor
      agonist U-50,488H did not affect the discriminative stimulus effects of cocaine,
      and the dose of U-50,488H which significantly induced aversive effects attenuated
      the rewarding effects of cocaine. OBJECTIVES: In the present study, the effects
      of a newly synthesized kappa-opioid receptor agonist, TRK-820, on the
      discriminative stimulus and rewarding effects of cocaine were examined in rats.
      METHODS: In the drug discrimination procedure, the effects of TRK-820 on the
      discriminative stimulus effects of cocaine were examined in rats that had been
      trained to discriminate between 10 mg/kg cocaine and saline. TRK-820-induced
      place preference or place aversion and the effects of TRK-820 on the cocaine (4
      mg/kg)-induced place preference were examined using a conditioned place
      preference procedure in rats. RESULTS: TRK-820 did not engender cocaine-like
      responding in rats trained to discriminate between 10 mg/kg cocaine and saline.
      In combination tests, low doses of TRK-820, which did not affect the response
      rate, significantly attenuated the discriminative stimulus effects of cocaine,
      and these effects of TRK-820 were reversed by a kappa-opioid receptor antagonist,
      nor-BNI. In the conditioned place preference procedure, low doses of TRK-820,
      which did not affect the response rate in the drug discrimination, did not
      produce either place preference or place aversion, whereas, higher dose (80
      microg/kg) of TRK-820 slightly but significantly induced a place aversion. Under
      these conditions, the cocaine-induced place preference was completely attenuated
      by low doses of TRK-820. These results may prompt further investigation of the
      effectiveness of the new kappa-opioid receptor agonist TRK-820 as a novel
      pharmacotherapeutic compound for the treatment of cocaine addiction.

PMID- 11967627
TI  - Sub-acute effects of MDMA (+/-3,4-methylenedioxymethamphetamine, "ecstasy") on
      mood: evidence of gender differences.
AB  - RATIONALE: Research with animals suggests that central 5-hydroxytryptamine (5-HT)
      function may be attenuated for a period following a single dose of +/-3,4
      methylenedioxymethamphetamine (MDMA, 'ecstasy'). If the same is true in humans,
      then functions thought to be modulated by 5-HT may differ in MDMA users compared
      with non-users a few days after the drug is taken. AIMS: The present study
      therefore investigated both acute and sub-acute effects of MDMA on mood of
      recreational users. A second aim was to determine whether these effects differ
      for females and males. DESIGN: A parallel group design was used to compare 40
      participants who reported taking MDMA with 40 participants who reported using
      illicit substances excluding MDMA (polydrug controls). Participants were assessed
      on the night of drug use (day 0) and again 4 days later. RESULTS: Female MDMA
      users showed higher depression scores mid-week than male users or male or female
      controls. Mid-week depression in female users was correlated with the amount of
      MDMA taken on day 0. MDMA users rated lower levels of aggression than controls on
      the night of drug use but significantly higher levels of aggression mid-week, and
      in males change in aggression correlated with the amount of MDMA taken on the
      weekend. There was no association between mood and measures of long-term use of
      MDMA (e.g. years of use). CONCLUSION: Women are more susceptible than men to mid
      week low mood following weekend use of MDMA; however, both men and women show
      increased self-rated aggression. These results are interpreted in terms of an
      attenuation of 5-HT function for a period following acute use of MDMA.

PMID- 11967628
TI  - Motor effects of acute and chronic inhibition of nitric oxide synthesis in mice.
AB  - RATIONALE: Systemic injections of nitric oxide synthase (NOS) inhibitors have
      been shown to decrease exploratory behavior in rats. This effect may be related
      to motor impairments since these drugs can induce catalepsy in rodents.
      OBJECTIVE: To compare the effects of two NOS inhibitors in tests aimed to
      investigate exploratory behavior and to assess motor control. METHODS: The acute
      effects of the NOS inhibitors NG-nitro- L-arginine ( L-NOARG, 10-80 mg/kg IP) and
      7-nitroindazole (7-NIO, 3-30 mg/kg IP) on exploratory activity were analyzed in
      an open field arena. Drug effects on catalepsy were examined in the hanging-bar
      and wire-ring test. Footprint pattern after treatment with the two NOS inhibitors
      was evaluated and the results compared with those obtained with the dopamine D2
      receptor antagonist haloperidol (1-2 mg/kg IP). Sub-chronic (twice a day for 4
      days) effects of L-NOARG (40 mg/kg) or 7-NIO (30 mg/kg) were also tested in the
      open field arena and catalepsy test. RESULTS: L-NOARG and 7-NIO decreased
      locomotion and rearing in the open field arena. Both drugs induced catalepsy in
      the hanging-bar test but did not change footprint pattern. The cataleptic effect
      of L-NOARG in the hanging bar and wire-ring tests were highly correlated (
      r=0.927). The exploratory and cataleptic effects of L-NOARG and 7-NIO provided
      evidence for tolerance after sub-chronic treatment. CONCLUSION: These results
      confirm that inhibition of neuronal NO formation induces impairment of
      exploratory behavior. This effect does not seem to involve aspects evaluated by
      footprint analysis, such as weight support, trunk stability and foot placement.
      They could, however, be related to drug-induced catalepsy.

PMID- 11967629
TI  - "Typical" but not "atypical" antipsychotic effects on startle gating deficits in
      prepubertal rats.
AB  - RATIONALE: Dopamine (DA) agonists and NMDA antagonists disrupt sensorimotor
      gating in rats, as measured by a loss of prepulse inhibition of the startle
      reflex. These effects are used in predictive models for antipsychotic efficacy:
      clinically "typical" and "atypical" antipsychotics restore PPI in adult rats
      treated with DA agonists such as apomorphine (APO), while clinically "atypical"
      antipsychotics restore PPI in rats treated with NMDA antagonists such as
      phencyclidine (PCP). We previously reported that the PPI disruptive effects of
      both APO and PCP are evident in 16- to 18-day-old rat pups, suggesting that the
      brain substrates for these effects are functional very early in development.
      OBJECTIVE: In the present study we assessed the developmental patterns of
      antipsychotic effects in these measures. METHODS: The PPI-disruptive effects of
      APO and PCP, and their antagonism by the typical antipsychotic haloperidol, and
      the atypical antipsychotic quetiapine, were assessed across development in
      Sprague-Dawley rats. RESULTS: Similar to the pattern seen in adults, both
      haloperidol and quetiapine opposed APO-induced PPI deficits in 16- to 19-day-old
      rat pups. However, the "atypical" antipsychotic quetiapine did not oppose PCP
      induced PPI deficits in pups or prepubertal (45 day) adolescents, but did oppose
      these PCP effects in postpubertal rats. CONCLUSIONS: While brain substrates
      mediating the PPI-disruptive effects of DA agonists and NMDA antagonists are
      functional early in development, some physiological event associated with puberty
      is a necessary condition for the "atypical antipsychotic profile" in this
      predictive model.

PMID- 11967630
TI  - Behavioral processes underlying the intake suppressive effects of melanocortin
      3/4 receptor activation in the rat.
AB  - RATIONALE: Central application of MTII, a melanocortin 3/4 receptor agonist,
      reduces food intake. The behavioral mechanisms underlying the anorexia, however,
      have not been evaluated. OBJECTIVES: We examined the ingestive behavioral effects
      of MTII at the microstructural level using two complementary approaches. METHODS:
      Rats were given daily 2-h sessions during which they drank 12.5% glucose
      solution; the time of occurrence of each lick event was recorded. We compared
      rats' glucose intake 30 min after the fourth ICV injection of 0.1, 0.33, and 1.0
      nmol MTII or vehicle. The licking patterns were examined to discern effects on
      parameters related to taste processes and others related to post-ingestive
      inhibitory feedback. A second experiment directly analyzed the effect of MTII on
      motor performance by examining whether drug treated rats would, like controls,
      adjust licking output to maintain meal size when lick volume was shifted from 8
      to 4 microl. RESULTS: Meal size was reduced by MTII in a dose-dependent manner
      (20-50%) in both experiments. Rats treated with MTII compensated for decreased
      lick volume by substantially increasing the number of licks emitted. Licking
      parameters associated with taste evaluation were not significantly affected by
      MTII, whereas parameters associated with post-ingestive inhibition varied as a
      function of treatment. CONCLUSIONS: Results suggest that MTII reduces intake by
      amplifying post-ingestive feedback inhibition. That MTII-treated rats increase
      the number of licks emitted in response to the lick volume reduction discounts
      the suggestion that intake inhibition is secondary to disruption of motor
      performance.

PMID- 11967631
TI  - Shared genes influence sensitivity to the effects of ethanol on locomotor and
      anxiety-like behaviors, and the stress axis.
AB  - RATIONALE: In rodents, a common response to many drugs of abuse, including
      ethanol (EtOH), is locomotor stimulation. It has been proposed, although debated,
      that EtOH-induced locomotor stimulation may represent an animal model of EtOH's
      euphoric effects. Another possibility is that this behavioral phenotype may
      represent an altered state of anxiety, and/or stress axis activation. OBJECTIVES:
      Mouse lines selectively bred for sensitivity (FAST) or resistance (SLOW) to
      EtOH's low dose locomotor stimulant effects were tested for differential
      sensitivity to EtOH's anxiolytic and/or stress axis activating effects, with the
      goal of detecting genetic correlations. METHODS: Saline- and EtOH-treated FAST
      and SLOW mice were tested on the elevated plus maze and the light-dark box, two
      widely used measures of anxiety-related behavior in rodents. In addition, serum
      corticosterone (CORT) levels were measured at various time points following
      injection of saline or ethanol. RESULTS: Behavioral data from both anxiety tests
      showed that FAST mice were less sensitive to EtOH's anxiolytic effects than were
      SLOW mice. Moreover, late recovery of elevated serum CORT levels following mild
      saline injection stress, as well as reduced CORT release in response to EtOH,
      suggested that FAST mice may possess a less responsive stress axis. CONCLUSIONS:
      These results provide evidence that sensitivity to the effects of EtOH on
      locomotor behavior, anxiety-like behavior, and the stress axis share some genetic
      influence.

PMID- 11967632
TI  - Inhibition by sigma receptor ligand, MS-377, of N-methyl- D-aspartate-induced
      currents in dopamine neurons of the rat ventral tegmental area.
AB  - RATIONALE: MS-377 [( R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl) piperazin-1
      yl]methyl-2-pyrrolidinone L-tartrate] is a novel anti-psychotic drug candidate
      with high affinity for sigma receptors but devoid of binding affinity for PCP
      binding site of NMDA receptor/ion channel complex. OBJECTIVES: The effects of MS
      377 on NMDA receptor and/or its ion channel complex were examined to elucidate
      the antipsychotic properties of MS-377. METHODS: We examined the effect of MS-377
      on NMDA ( N-methyl- D-aspartate)-induced current in acutely dissociated dopamine
      neurons of rat ventral tegmental area (VTA) using patch clamp whole cell
      recording. RESULTS: MS-377 applied in a bath inhibited the peak current evoked by
      NMDA applied via the U-tube method for 2 s in a concentration-dependent manner.
      Other sigma receptor ligands, BD-1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4
      methylpiperazine), NE-100 ( N, N-dipropyl-2-[4-methoxy-3-(2-phenylenoxy)-phenyl]
      ethylamine monohydrochloride) and haloperidol also inhibited NMDA-induced current
      in a concentration-dependent manner. Interestingly, concomitant application of MS
      377 with BD-1063, NE-100 or haloperidol at concentrations that had no effects on
      NMDA-induced current, potentiated the MS-377-induced inhibition. CONCLUSIONS: The
      results suggest that MS-377, as well as other sigma receptor ligands, indirectly
      acts on the sigma receptor to inhibit glutaminergic transmission mediated by NMDA
      receptor/ion channel complex in VTA dopamine neurons, thereby inhibiting dopamine
      release in target VTA areas.

PMID- 11967634
TI  - The melanocortin receptor agonist MTII augments the rewarding effect of
      amphetamine in ad-libitum-fed and food-restricted rats.
AB  - RATIONALE: Numerous forms of evidence support a functional association between
      drug-seeking and ingestive behavior. One example is the augmentation of rewarding
      and cellular-activating effects of abused drugs by chronic food restriction.
      Within the past several years, a variety of orexigenic and anorexigenic
      neuropeptides that mediate adaptive responses to changes in energy balance and
      body weight have been identified. The involvement of these neuropeptidergic
      signaling systems in the modulation of drug reward has received little
      experimental attention. alpha-Melanocyte-stimulating hormone (alpha-MSH) and
      agouti-related protein, which act as agonist and antagonist, respectively, at
      melanocortin receptors (MCRs), are of particular interest because of their
      neuroanatomical distribution and opponent actions at a common receptor type.
      OBJECTIVES: The objective of this study was to determine whether lateral
      ventricular (i.c.v.) injections of the MCR agonist MTII and MCR antagonist
      SHU9119 at doses that decrease and increase food intake, respectively, modify the
      rewarding effect of amphetamine. METHODS: The rewarding effect of amphetamine was
      measured in terms of its ability to lower the threshold for lateral hypothalamic
      self-stimulation (LHSS) using a rate-frequency method. The modulatory effects of
      MTII and SHU9119 were evaluated by preceding i.c.v. amphetamine injection with
      i.c.v. injection of one of these MCR ligands or vehicle. Tests were conducted in
      both ad-libitum-fed and food-restricted subjects. RESULTS: SHU9119, the agouti
      related protein-like antagonist, markedly increased overnight food intake of ad
      libitum-fm-fed rats following i.c.v. injection of 1.0 microg and 0.5 microg.
      However, these injections had no effect on thresholds for LHSS tested 25 min or
      60 min post-injection, nor did they alter the threshold-lowering effect of
      amphetamine (50 microg) tested 25 min, 100 min, or 24 h post-injection. MTII, the
      alpha-MSH-like agonist, suppressed overnight food intake of ad-libitum-fed rats
      following i.c.v. injection of 1.0 microg. MTII had no effect on thresholds for
      LHSS tested 60 min post-injection. However, this MCR agonist potentiated the
      threshold-lowering effect of amphetamine tested 100 min but not 24 h post
      injection. This effect was evident in both ad-libitum-fed and food-restricted
      rats. CONCLUSIONS: These results indicate that agonist activity at MCRs
      potentiates amphetamine reward and that the anorexigenic neuropeptide alpha-MSH
      may exert this effect physiologically.

PMID- 11967635
TI  - Orally delivered alprazolam, diazepam, and triazolam as reinforcers in rhesus
      monkeys.
AB  - RATIONALE: Benzodiazepines are among the most frequently prescribed drugs and are
      usually taken by mouth. However, there have been few studies of oral self
      administration of these drugs, and the results of IV self-administration studies
      indicate that benzodiazepines are modest reinforcers. OBJECTIVES: To determine if
      orally delivered alprazolam, diazepam, and triazolam could serve as reinforcers
      for rhesus monkeys, and to determine some of the conditions under which
      benzodiazepine reinforced behavior occurs. METHODS: Diazepam or midazolam was
      initially established as a reinforcer by a fading procedure whereby increasing
      concentrations were added to a 1 or 2% ethanol solution, and subsequently the
      ethanol concentration was decreased in steps to zero. Diazepam- and midazolam
      reinforced responding persisted in the absence of ethanol. Triazolam and
      alprazolam served as reinforcers when substituted for diazepam or midazolam.
      RESULTS: Alprazolam, diazepam, and triazolam served as effective reinforcers
      across a wide range of concentrations and under fixed-ratio sizes of 16 and 32.
      Rates of responding were usually far higher than that for the concurrently
      available vehicle, water. Drug intake (mg drug/kg body weight) generally
      increased with increases in drug concentration. When large drug amounts were
      consumed, signs of intoxication were observed. CONCLUSIONS: In contrast to
      reports of low response rates and weakly maintained behavior, the present results
      show that the three benzodiazepines can serve as effective reinforcers.

PMID- 11967633
TI  - Brain potential signs of slowed stimulus processing following cholecystokinin in
      Parkinson's disease.
AB  - RATIONALE: Cholecystokinin (CCK) is a neuropeptide which is colocalized with
      dopamine (DA) in neurons of the mesolimbic-frontocortical and nigrostriatal DA
      system. In animals CCK enhances DA activity in these systems. OBJECTIVES: The
      present study examined the effects of a single intranasal administration of CCK-8
      on auditory brain potential (AEP) signs of cognitive processing and on motor
      performance in patients with Parkinson's disease (PD), known to originate from
      degeneration of DA neurons primarily in the nigrostriatal DA system. METHODS:
      Thirteen PD patients were examined after medication withdrawal, on two occasions
      after administration of placebo and 25 microg CCK-8, and compared with healthy
      controls matched for age and sex. AEPs were recorded while subjects performed an
      attention task (oddball paradigm). RESULTS: In the placebo condition, AEPs in the
      PD patients did not show marked alteration but were rather comparable to those in
      the controls. In healthy controls, CCK-8 enhanced the P3 complex ( P<0.05) and
      shortened latencies of the N2 and P3 components of the AEP evoked by task
      relevant target stimuli ( P<0.05). Contrary to expectations, in PD patients these
      AEP components were distinctly delayed after CCK-8 ( P<0.05). Motor performance
      was not changed by CCK-8 in PD patients or in controls. CONCLUSION: Data indicate
      a deleterious rather than beneficial effect of CCK on cognitive processing in PD
      patients that might result from a prevailing effect of the neuropeptide on
      transmitter systems (e.g. GABAergic) other than the DA system.

PMID- 11967636
TI  - Serotonin in cisternal cerebrospinal fluid of rhesus monkeys: basal levels and
      effects of sertraline administration.
AB  - RATIONALE: Studies of rodents suggest that extracellular fluid and cerebrospinal
      fluid (CSF) serotonin (5-HT) concentrations provide a better index of released 5
      HT than the frequently obtained measure of CSF 5-hydroxyindoleacetic acid (5
      HIAA). The measurement of cisternal CSF 5-HT levels in the monkey might offer a
      method of assessing the effects of agents and actions on central 5-HT functioning
      in primate brain. OBJECTIVE: To address methodological issues related to the
      determination of monkey cisternal CSF 5-HT and to examine the effects of a
      selective serotonin reuptake inhibitor (SSRI) on the measure. METHODS: Monkey CSF
      was obtained by cisternal puncture and 5-HT levels determined by high performance
      liquid chromatography, after screening for blood contamination. RESULTS: When
      blood contamination was minimized, a mean (+/-SD) basal concentration of
      cisternal CSF 5-HT 87+/-36 pg/ml (n=13) was observed. Good longitudinal stability
      (variances of 16 and 20%) of CSF 5-HT was demonstrated in two monkeys sampled
      over a 3-month period. A two-fold increase in CSF 5-HT was seen in seven animals
      treated with the SSRI sertraline (20 mg/kg PO, mean treatment period of 12 days):
      pre- and post-drug 5-HT concentrations were 85+/-39 and 162+/-53 pg/ml
      (P=0.0007); in contrast, levels of 5-HIAA decreased from 40.0+/-5.7 to 20.4+/-2.2
      ng/ml (P=0.0001). CONCLUSIONS: The measurement of monkey cisternal CSF 5-HT
      appears to provide a useful index of central 5-HT release. Initial results tend
      to support a role for increased extracellular 5-HT in the mechanism of action of
      chronically administered SSRIs.

PMID- 11967637
TI  - Effects of dopamine D4 receptor-selective antagonists on motor hyperactivity in
      rats with neonatal 6-hydroxydopamine lesions.
AB  - RATIONALE: Dopamine D4 receptor gene polymorphism has been repeatedly associated
      with attention deficit hyperactivity disorder (ADHD) and related personality
      traits. We recently reported that motor hyperactivity in an animal model of ADHD
      was dose-dependently reversed by CP-293,019, a D4 receptor-selective antagonist.
      However, behavioral effects of this agent may not be attributed exclusively to D4
      receptor blockade, since it interacts with other sites including serotonin
      receptors. OBJECTIVES: To test further the hypothesis that D4 receptor blockade
      can reduce motor hyperactivity, behavioral effects of three chemically and
      pharmacologically dissimilar D4 antagonists were compared to that of ketanserin,
      a serotonin 5-HT(2A/2C) antagonist. METHODS: Selective dopamine lesions were made
      in male rats at postnatal day (PD) 5 with intracisternal 6-hydroxydopamine (100
      microg) after desipramine pretreatment (25 mg/kg, SC) to protect noradrenergic
      neurons. Effects of D4 receptor-selective antagonists and ketanserin on lesion
      induced motor hyperactivity were examined during the periadolescent period
      (postnatal days 23-26) with an infrared photobeam activity system. RESULTS: The
      D4 antagonists L-745,870 and U-101,958 dose-dependently inhibited motor
      hyperactivity in rats with neonatal lesions, whereas S-18126 lacked this effect
      at doses up to 30 mg/kg. None of these drugs affected motor behavior in sham
      control rats. In contrast, ketanserin produced apparent sedative effects in both
      lesioned and intact control rats without normalizing hyperactivity. CONCLUSIONS:
      Motor hyperactivity in this ADHD model was selectively antagonized by three of
      four dopamine D4 receptor antagonists evaluated, encouraging clinical assessment
      of D4 antagonists in patients with ADHD.

PMID- 11967638
TI  - Trough oestradiol levels associated with cognitive impairment in post-menopausal
      women after 10 years of oestradiol implants.
AB  - RATIONALE: Oestrogen treatment has been found to improve memory in healthy post
      menopausal women, but the effects are small, especially when socio-economic
      status is controlled. There is some evidence that with long-term treatment the
      benefits decline, or reverse. OBJECTIVE: To examine the effects of 10 years of
      oestradiol implants on attention, memory and frontal lobe function in healthy
      women (aged 51-72 years) who had undergone a surgical menopause. METHODS: In an
      open study, patients were recruited from the Guy's Hospital menopause clinic and
      were tested just before receiving a new implant. Exclusion criteria included any
      form of psychoactive medication, IQ<90, English not the first language and
      anxiety or depression scores in the clinical range. All patients had been
      receiving HRT with an oestradiol implant for about 10 years. Each patient was
      pair-matched to a woman who had never received HRT. Eighteen pairs were matched
      for age, IQ, socio-economic status, years of secondary education, and occupation.
      They completed questionnaires, mood rating scales and a battery of cognitive
      tests. RESULTS: The patients with oestradiol implants had significantly greater
      psychological and somatic menopausal symptoms and significantly worse mental
      flexibility (rule reversal) and long-term episodic memory than did the control
      group who had never received HRT. Analysis of covariance showed that the
      difference in menopausal symptoms did not account for the cognitive differences.
      There were no differences in a test of sustained attention or in a category
      generation task or in self-ratings of mood after the stress of cognitive testing.
      CONCLUSIONS: Long-term treatment with oestradiol implants does not convey
      cognitive benefits and may lead to impaired function.

PMID- 11967639
TI  - Can malondialdehyde be used as a biological marker of progression in
      neurodegenerative disease?
AB  - There is a large body of evidence that free radical-mediated oxidative damage is
      involved in the pathogenesis of neurodegenerative disease. Although it is
      unlikely that markers of such damage will have any diagnostic value, they might
      be of considerable interest in following disease progression and monitoring the
      efficacy of different treatments. Among such markers, there is evidence for the
      elevation of peripheral malondialdehyde levels in several neurodegenerative
      diseases, including Parkinson's disease, amyotrophic lateral sclerosis and
      Alzheimer's disease. The measurement of malondialdehyde levels, which is both
      simple and cheap to perform, can and should be incorporated into future clinical
      trials. This will allow a clearer picture to emerge as to whether malondialdehyde
      can be considered as a marker for the evolution of these diseases.

PMID- 11967640
TI  - Oligoclonal bands and antibody responses in multiple sclerosis.
AB  - Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System
      with multifocal areas of demyelination. Although its etiology and pathogenesis
      remain controversial, several lines of evidence indicate that MS is mediated by a
      misdirected immune response against one or several myelin proteins. The
      involvement of diverse leukocyte subsets and their products in MS is still the
      subject of considerable debate. The emphasis on T cells has derived mainly from
      the detection of activated T cells in MS plaques and analogies with animal models
      of MS. Because of these observations cell-mediated immunity has dominated the
      research field of MS to this day. However, in recent years the role of B cells,
      plasma cells and immunoglobulins in MS have been re-examined, and current
      findings indicate that humoral immunity also plays a major role in disease
      pathogenesis. B cells and their products could exert several potential effects
      during the course of MS. Firstly, autoantibodies against specific myelin antigens
      could mediate damage to myelin membranes. Secondly, some studies suggest that
      natural autoantibodies could enhance remyelination. Thirdly, antibodies directed
      against myelin components can participate in anti-idiotypic networks, which may
      regulate the course of MS. Increased intrathecal immunoglobulin synthesis
      reflected by raised IgG indices and an oligoclonal pattern is the most common
      abnormality detected in MS patients. The introduction of more sensitive
      procedures for protein detection has allowed demonstrating oligoclonal bands
      (OCBs) in up to 95 % of patients with clinically definite MS. Although the
      presence of OCBs in CSF of MS patients is now well established as a sensitive
      laboratory test to support the clinical diagnosis, OCBs may be present in other
      disorders, including those not directly related to infection or abnormal immune
      response. Nevertheless, the pathogenesis of OCBs in MS is still obscure, and
      despite extensive research their antigenic target(s) have yet to be established.
      Therefore, a critical task is to identify the specificity of such target(s), thus
      providing significant clues about MS etiology. For this purpose, novel molecular
      immunologic strategies have been recently developed to offer alternative
      approaches to identify putative antigens recognized by antibodies present in MS
      patients. The elucidation of the mechanisms and target(s) responsible for the
      onset of MS has obvious implications for the further development of specific
      therapies.

PMID- 11967641
TI  - Neurological research in Europe, as assessed with a four-year overview of
      neurological science international journals.
AB  - This paper analyses all the peer-reviewed articles published by European authors
      in 161 neurological journals screened by ISI in accordance with Current
      Contents/Life Science and Current Contents/Clinical Medicine in the period 1995
      1998. Our aim was to report the amount and quality of neurological research in
      the different countries of the European Union (EU), the USA and the world. The
      number of papers, the impact factors (IF), the population of the source country
      and gross domestic product (GDP), were downloaded. Data show that in the EU there
      is a progressive increase in the number of published papers from 1995 to 1998 and
      that large countries such as Germany, the United Kingdom, France and Italy rank
      at the top four places for absolute number of papers. The gap in the number of
      papers between the USA and the EU significantly diminished in the examined
      period, from a difference of 14 % to 6 %. However, when the IF is considered, the
      USA performed better than EU, although excellent results have been obtained by
      the United Kingdom, Ireland, Netherlands and Sweden. When the number and quality
      of papers are plotted against the number of inhabitants or GDP, Sweden, the
      Netherlands and Finland are the leading countries in Europe. The present study
      demonstrates that neurological research in the EU is active and productive, is
      steadily increasing and is now a relevant part of all biomedical world research.

PMID- 11967642
TI  - Low dose sodium valproate in the treatment of juvenile myoclonic epilepsy.
AB  - Fourteen patients with juvenile myoclonic epilepsy (JME) were treated with a
      single low dose of a sustained-release preparation of sodium valproate (VPA, 500
      mg daily). The mean age of the onset of the low dose treatment was 19.2 years
      (range 14-26). Before this treatment, six patients had been treated with high
      dose VPA for a period of more than 2 years, three patients for 1 to 2 years,
      three patients less than 1 year and two patients initiated the treatment from the
      beginning with a low dose. The mean duration of low dose treatment is 35.6 months
      (range 25-59 months). (All patients are still under medication). Generalized
      tonic-clonic and absence seizures were controlled in all patients. Myoclonic
      jerks relapsed only in one patient, a young mother who was looking after her
      newly born baby and was deprived of sleep. No adverse reactions have been
      reported. We suggest that JME patients can effectively be treated with single low
      VPA dose (500 mg daily), while at the same time seizure precipitating factors,
      such as sleep deprivation and alcohol ingestion, should be avoided.

PMID- 11967643
TI  - Comparison of electrodiagnostic criteria for demyelination in patients with
      chronic inflammatory demyelinating polyneuropathy (CIDP).
AB  - This study compared sensitivity, specificity, positive and negative likelihood
      ratios (LR) of four previously published sets of electrodiagnostic criteria for
      demyelination in 64 patients whose history and physical examination indicated
      that chronic inflammatory demyelinating polyneuropathy was a possible diagnosis.
      Sensitivity of the sets of criteria ranged from 56-70 % and specificity from 85
      98 %. Positive LRs ranged from 4.67-28 and negative LR's from 0.35-0.45. The
      results showed that one set of electrodiagnostic criteria was considerably more
      helpful than the other three in establishing the diagnosis CIDP. If, however, the
      test results of the sets were not consistent with demyelination, the effect of
      the negative test results on the probability of the diagnosis CIDP was similar
      for all four sets.

PMID- 11967644
TI  - Former poliomyelitis as a health and socioeconomic factor. A paired sibling
      study.
AB  - Eighty former poliomyelitis patients and the sibling nearest in age and of same
      sex were examined with matched-pair analysis to evaluate the effect of previous
      poliomyelitis (polio) on social factors and general health. Fifty-four pairs with
      women (68 %), and 26 pairs with men (32 %) with a mean age 60.4 years were
      included. Data were collected by questionnaire. There was no significant
      difference in length of education between patients and siblings (categories < 8
      years, 8-12 years, and > 12 years). Employment rate at age 40 years was 78 % for
      patients and 88 % for siblings (full-time or part-time); this difference was not
      significant. Educational options were considered to have been excellent by 38 %
      of the patients and 26 % of the siblings (not significant), with a fair agreement
      within the pairs (kappa=0.31). There was no significant difference regarding
      professional options; rated as excellent by 33 % of patients, and 28 % of
      siblings, with a fair agreement (kappa=0.25) also for this issue. Perception of
      general health today expressed on a horizontal VAS-scale (0-10) was significantly
      lower among the patients than the siblings, mean values of 5.8 and 6.8 (P <
      0.001) respectively. Patients also reported a lower quality of life (P=0.03), and
      less energy for leisure activities (P=0.008). Post polio symptoms like muscular
      and articular pain, and abnormal tiredness were more common among patients than
      siblings, whereas there was no difference regarding coexisting illness. In
      conclusion, polio patients and their siblings reckoned their educational and
      professional options to have been at the same level. The patients were well
      educated and employed to the same degree up to the age of 40 years, but now at a
      higher age reported reduced general health.

PMID- 11967645
TI  - Neurological manifestations of Behcet's disease in a Caribbean population:
      clinical and imaging findings.
AB  - Behcet's disease (BD) is a chronic relapsing multisystem disorder. While most
      frequently occurring around the Mediterranean and in Japan, isolated cases of BD
      have been reported in Africa south of the Sahara and in the Caribbean. The aim of
      this study was to describe our experience of BD in Guadeloupe (French West
      Indies) where the presence of the disease has not been reported previously. We
      analysed retrospectively the charts, and clinical and imaging features of
      patients native to Guadeloupe who were diagnosed with neurological manifestations
      of BD between 1989 and 1999. In our series of 13 cases, seven had neurological
      involvement. Neurological manifestations included meningoencephalitis or
      meningoencephalomyelitis in four cases, cerebral venous thrombosis in one case
      and peripheral neuropathy in two cases associated with myositis in one. Patients
      received treatment with colchicine (n=7), corticosteroids (n=6),
      immunosuppressive therapy (azathioprine and/or cyclophosphamide; n=4),
      acetylsalicylic acid (n=2) and oral anticoagulation for venous thrombosis (n=1).
      Long-term sequelae occurred only in patients with recurrent neurological disease.
      This study suggests that the frequency of BD in this Afro-Caribbean population is
      higher than this reported in Caucasian populations. Meningoencephalitis is
      associated with a poor prognosis while other patients achieved recovery.

PMID- 11967646
TI  - How common are complications of Parkinson's disease?
AB  - BACKGROUND: Parkinson's disease (PD) can be associated with a wide range of
      complications of advancing disease and treatment. However, it is unclear how
      often these occur in the overall population of patients with PD. OBJECTIVE: To
      assess the prevalence of disease and treatment complications and their clinical
      correlates in a community-based sample of 124 patients with PD. RESULTS: Average
      current age was 72 (SD 10.9) and mean disease duration 6 (SD 4.3) years. Falls
      with postural instability and other axial features were among the most common
      complications of advancing disease in this population (64 %). Motor fluctuations
      and dyskinesias affected approximately 30 and 20 % of the overall sample
      respectively, and changes in mental state such as dementia, depression and
      hallucinations each affected approximately one fifth of patients. Symptoms of
      autonomic nervous system dysfunction occurred in the great majority of patients,
      but were not associated with greater disease severity, disease duration or
      overall disability. CONCLUSION: In contrast to clinic-based samples, the most
      frequently occurring complications of PD in this community-based sample were
      axial features such as postural instability with falls. These factors should be
      more taken into account in the allocation of health care resources and the
      treatment of symptoms of patients with PD in the community.

PMID- 11967647
TI  - Effects of nonenzymatic glycosylation of extracellular matrix components on cell
      survival and sensory neurite extension in cell culture.
AB  - Diabetic sensory polyneuropathy is characterized by a distal axonopathy of dying
      back type. It is accompanied by a failure of axonal regeneration, in which
      nonenzymatic glycosylation (glycation) of the extracellular matrix may be
      involved. In the present study, the effects of glycation of collagen IV and
      laminin, major components of basal lamina, on neuron survival and neurite
      extension were investigated in tissue culture. Fast glycation of laminin was
      achieved by incubation with glycolaldehyde and glycation of collagen IV by
      incubation with glucose. The degree of glycation was estimated by fluorescence
      analysis. Glycated or nonglycated laminin or collagen IV were used as substrates
      for culture of dorsal root ganglion (DRG) neurons from neonatal rats. Cultures
      were assessed for the proportion of cells attaching to the substrate, surviving
      and bearing neurites. Cell attachment and the proportion bearing neurites were
      significantly reduced on collagen IV glycated for 2 weeks, but survival was only
      affected by glycation for 4 or 5 weeks. All 3 parameters were significantly
      reduced on glycated compared with unglycated laminin. Glycation of both laminin
      and collagen IV produced considerable morphological differences in the cultured
      neurons on scanning electron microscopy. Dissociated DRG neurons from adult
      animals with streptozotocin-induced diabetes cultured on nonglycated substrates
      survived less well and produced fewer neurites. Glycation of collagen IV and
      laminin thus affects neuronal survival, neurite production and cell morphology,
      and diabetes affects both the survival of sensory neurons in culture and their
      ability to extend neurites.

PMID- 11967648
TI  - Late onset ataxia phenotype in dentatorubro-pallidoluysian atrophy (DRPLA).
AB  - ABSTRACT We clinically and genetically studied three patients in a family with
      dentatorubro-pallidoluysian atrophy (DRPLA). The proband patient had 58/24 CAG
      repeat alleles of the DRPLA gene (normal < or = 34 repeats). Cerebellar ataxia
      first developed in the 6-7th decades and was the predominant feature for more
      than 10 years in all three, after which two of them manifested dementia and
      choreiform movements in the advanced stage. Atrophy of the cerebellum and brain
      stem an CT or MRI had suggested dominant spinocerebellar ataxia as a diagnosis in
      their ataxia-predominant stage, with a diagnosis of DRPLA being impossible based
      on the clinical findings alone. Our experience implies that DRPLA must be taken
      into account in the differential diagnosis of late onset ataxic disorders, since
      it can easily be overlooked.

PMID- 11967649
TI  - Bradykinesia in Huntington's disease. A prospective, follow-up study.
AB  - Bradykinesia is a frequent finding in Huntington's disease (HD), but some aspects
      are presently unknown; including the natural evolution of bradykinesia over time
      and the correlation between bradykinesia and functional capacity. We studied the
      motor performance of 20 genetically confirmed patients with HD (age: 40+/-10.8
      years; age at onset 33.6+/-11 years; total functional capacity (TFC): 9.57+/-3;
      UHDRS total motor scale: 31.4+/-13, triplet length (CAG)n: 46.7+/-4 triplets).
      These patients were studied in baseline conditions and after 18.7+/-6 months of
      follow-up. In addition, HD patients were compared with 20 age-matched normal
      controls. Motor study included the four CAPIT timed tests commonly used for
      Parkinson's disease: pronation-supination (PS), finger dexterity (FD), movement
      between two points (MTP) and walking test (WT). HD patients were significantly
      slower than controls in all motor tasks. A significant deterioration occurred
      over time in three of the four motor tasks (especially FD and WT). A significant
      correlation between timed tests and TFC score was found (for MTP, r: -0.845; p <
      0,0001). In addition a significant correlation between timed tests and the UHDRDS
      total motor scale was also found (for MTP, r: 0.864; p < 0.0001). In conclusion,
      simple timed motor tests can detect a deterioration of motor activity over time
      in HD. Timed tests might be useful to follow the natural evolution of HD and to
      assess the efficacy of new therapies.

PMID- 11967650
TI  - Seasonal occurrence of relapses in inflammatory myopathies: a preliminary study.
AB  - The seasonal occurrence of relapses was analysed retrospectively in a group of 53
      patients with treated dermatomyositis (DM) or polymyositis (PM). In DM, the
      incidence of both myositic and cutaneous relapses was highest in summer whereas
      in the PM group relapses was more evenly distributed throughout the seasons but
      lowest in summer. The present findings suggest that environmental factors such as
      intercurrent infections and light exposure may be involved in reactivating the
      disease process and causing relapses in DM but less so in PM. Further prospective
      studies are needed to assess the role of environmental factors in the initiation
      and reactivation of the inflammatory myopathies.

PMID- 11967651
TI  - Glycerol for acute stroke: a Cochrane systematic review.
AB  - Brain oedema is a major cause of early death after stroke. Glycerol is a
      hyperosmolar agent that is claimed to reduce brain oedema. We sought to determine
      whether I. V. glycerol treatment in acute stroke, either ischaemic or
      haemorrhagic, influences death rates and functional outcome in the short or long
      term and whether the treatment is safe. The Cochrane Stroke Group Trials Register
      was searched, conference proceedings were screened and some trialists were
      personally contacted. We considered all completed, controlled, published and
      unpublished comparisons, evaluating clinical outcome, in which intravenous
      glycerol treatment was initiated within the first days after stroke onset. Death
      from all causes, functional outcome and adverse effects were analysed. Analysis
      of short term death for acute ischaemic and/or haemorrhagic stroke was possible
      in ten trials where 482 glycerol treated patients were compared with 463 control
      patients. Glycerol was associated with a non-significant reduction in the odds of
      death within the scheduled treatment period (OR 0.78, 95 % Confidence Intervals
      0.58-1.06). Among patients with definite or probable ischaemic stroke, glycerol
      was associated with a significant reduction in the odds of death during the
      scheduled treatment period (odds ratio 0.65, 95 % CI 0.44-0.97). However, at the
      end of the scheduled follow up period there was no significant difference in the
      odds of death (odds ratio 0.98, 95 % CI 0.73-1.31). Functional outcome was
      reported in only two studies and there was a non-significant positive effect on
      outcome at the end of scheduled follow up (odds ratio 0.73, 95 % CI 0.37-1.42).
      Haemolysis seems to be the only relevant adverse effect of glycerol treatment.
      This systematic review suggests a favourable effect of glycerol treatment on
      short term survival in probable or definite ischaemic stroke, but the magnitude
      of the treatment effect may be minimal (as low as a 3 % reduction in odds).
      Because of the relatively small number of patients and because the trials have
      been performed in the pre-CT era, the results must be interpreted cautiously. The
      lack of evidence of benefit in long term survival does not support the routine or
      selective use of glycerol treatment in patients with acute stroke.

PMID- 11967652
TI  - Bell's palsy-induced blepharospasm.
AB  - We report two patients with blepharospasm that appeared during the recovery phase
      of Bell's palsy. It is well known that hemifacial spasm occasionally appears
      after Bell's palsy; however, blepharospasm associated with Bell's palsy has been
      rarely reported so far. Blepharospasm appeared within a month after the onset of
      Bell's palsy, suggesting that a certain causal relationship may be present
      between Bell's palsy and blepharospasm. We speculate that corneal irritation
      caused by lagophthalmos contributes to the induction of blepharospasm. Another
      speculation is that abnormal afferent input from the paralyzed side contributes
      to the abnormal sensitization of the blink reflex, thereby facilitating the
      induction of abnormal facial motor outputs such as blepharospasm.

PMID- 11967653
TI  - Blood supply of the posterior cerebral artery by the carotid system on
      angiograms.
AB  - BACKGROUND AND PURPOSE: Occipital lobe infarcts are traditionally attributed to
      vertebrobasilar disease. However, anatomical studies indicate that in some people
      the supply of the posterior cerebral artery is via the carotid system. We
      investigated how often such a developmental variant in the cerebral blood supply
      was present during life. METHODS: We retrospectively studied 212 conventional
      four-vessel cerebral angiograms. Eighteen subjects were excluded beforehand,
      because of vascular abnormalities causing important hemodynamic changes. We
      determined whether a fetal variant was present, and in other cases whether there
      was a functioning posterior communicating artery. RESULTS: In 11 % of hemispheres
      the posterior cerebral artery was exclusively supplied by the internal carotid
      artery; in a further 46 % of hemispheres the internal carotid artery might
      contribute, via a patent posterior communicating artery. In 75 % of subjects the
      internal carotid artery contributed in at least one hemisphere to the blood flow
      of the posterior cerebral artery. CONCLUSIONS: The implication of our findings is
      that an occipital lobe infarct can be caused by ipsilateral carotid disease in a
      proportion of cases between 10 and 60 %. This implies that carotid endarterectomy
      might be beneficial in some patients with severe carotid stenosis and infarction
      in the territory of the posterior cerebral artery.

PMID- 11967654
TI  - Reading errors in patients with cerebellar vermis lesions.
AB  - Dyslexia, both developmental and acquired, has been considered the result of
      cerebrocortical dysfunction, affecting the temporo-parieto-occipital brain
      regions. However, dyslexia may involve abnormalities of the magnocellular
      component of the visual system, leading to binocular instability or alterations
      of accommodation. To test the hypothesis of cerebellar involvement in the reading
      process -- justified by its emergent role in language and cognition -- we studied
      10 patients with cerebellar vermis/paravermis lesions using reading tests and we
      compared the results with those produced by 10 normal volunteers. The data
      obtained demonstrate an increased number of reading mistakes in the patient
      group, resulting from a possible alteration of the diffuse connection system from
      the cerebellum to different cerebrocortical and subcortical structures. Acquired
      dyslexia due to cerebellar impairment may be due to oculomotor alteration or,
      more subtly, to the intimate cerebellar-encephalic projections, connecting the
      cerebellum to the attentive and alerting processes and to the language system. We
      discuss the data with an overview of literature.

PMID- 11967655
TI  - Visual field constriction in epilepsy patients treated with vigabatrin and other
      antiepileptic drugs: a prospective study.
AB  - BACKGROUND: Visual field constriction (VFC) has been described in about 30 % to
      50 % of patients treated with the antiepileptic drug (AED) Vigabatrin (GVG). The
      exact incidence of VFC related to GVG exposure is unknown. Risk factors other
      than medication have not been identified as yet, and it is unclear whether the
      occurrence of VFC is restricted to the use of GVG. METHODS: In a longitudinal
      study, we investigated 60 epilepsy patients who received GVG and other AEDs.
      Patients underwent full ophthalmological examination including perimetry.
      RESULTS: 16 of 60 patients exposed to different AEDs developed VFC, which was
      judged as clinically relevant by an experienced neuroophthalmologist. VFC was
      observed significantly more often in patients treated with GVG as add-on- or
      monotherapy as compared with patients who had never been exposed to GVG (13/29
      versus 3/31). Within the subgroup of 23 patients who received GVG as add-on
      therapy, those who developed VFC had been exposed to GVG for significantly longer
      than patients without VFC. The only non-treatment related feature associated with
      VFC was older age. Type and severity of epilepsy or type and number of
      concomitant AED were not related to the occurrence of VFC. CONCLUSIONS: The
      findings of an overrepresentation of VFC in patients receiving GVG and of a
      correlation between duration of GVG treatment and occurrence of VFC support the
      causal role of GVG treatment in the development of VFC. Old age is a possible
      risk factor for the development of VFC associated with GVG in epilepsy patients.

PMID- 11967656
TI  - Auditory-visual synaesthesia in a patient with basilar migraine.

PMID- 11967657
TI  - Intracerebral hemorrhages, fibrinolysis, and prostate carcinoma.

PMID- 11967658
TI  - Creutzfeldt-Jakob disease after Jannetta's operation with cadaveric dura mater
      graft: initial manifestations related to the grafted site.

PMID- 11967659
TI  - Pancreatitis complicating treatment with intravenous valproic acid.

PMID- 11967660
TI  - Sleep-related painful erection is associated with neurovascular compression of
      basal forebrain.

PMID- 11967661
TI  - Is clonidine-growth hormone stimulation a good test to differentiate multiple
      system atrophy from idiopathic Parkinson's disease?

PMID- 11967662
TI  - Fluctuating peroneal nerve palsy caused by an intraneural cyst.

PMID- 11967663
TI  - Rudolf Ludwig Karl Virchow (1821-1902).

PMID- 11967666
TI  - Disruption of Hoxb8 gene leads to obsessive grooming behavior.

PMID- 11967668
TI  - Guidelines for granting of privileges for gastrointestinal endoscopy: focus on
      outcomes not number of procedures performed.

PMID- 11967669
TI  - Laparoscopic adjustable silicone gastric banding for morbid obesity: results and
      complications in 715 patients.
AB  - BACKGROUND: Laparoscopic adjustable silicone gastric banding (LASGB) was used as
      the initial bariatric procedure for more than 36 months. The efficacy and safety
      of LASGB were studied. METHODS: Patients were followed up prospectively in a
      multidisciplinary center for the perioperative and long-term courses, and for
      complications. RESULTS: Between November 1996 and May 1999, 715 patients
      underwent surgery. The mean age was 34.6 years (range, 16-72) years, and the mean
      body mass index (BMI) was 43.1 kg/m2 (range, 35-66 kg/m2). The mean operative
      time was 78 min (range, 36-165 min), and the postoperative hospitalization time
      was 1.2 days (range, 1-8 days). There were six intraoperative complications
      (0.8%), eight early postoperative complications (1.1%), and no deaths. For follow
      up evaluation, 614 patients (86%) were available. Late complications included
      band slippage or pouch dilation in 53 patients (7.4%), band erosion in 3
      patients, and port complications in 18 patients. In 57(7.9%) patients, 69 major
      reoperations were performed. In patients with a follow-up period longer than 24
      months, the average BMI dropped from 43.3 kg/m2 (range, 35-66 kg/m2) to 32.1
      kg/m2 (range, 21-45 kg/m2). CONCLUSION: Laparoscopic adjustable silicone gastric
      banding is safe, with a lower complication rate than any other bariatric
      procedure. Most reoperations can be performed laparoscopically with low morbidity
      and short hospitalizations. On the basis of intermediate-term follow-up
      evaluation, it is an effective procedure for weight-reducing purposes.

PMID- 11967670
TI  - Prospective randomized trial comparing conventional laparoscopic colectomy with
      hand-assisted laparoscopic colectomy: applicability, immediate clinical outcome,
      inflammatory response, and cost.
AB  - BACKGROUND: Hand-assisted laparoscopic surgery (HALS) represents a useful
      alternative to conventional laparoscopic surgery (LS). Its potential advantages-
      (a quicker, safer procedure and less need to convert to open surgery) are due to
      the recovery of tactile feedback. However, HALS requires the performance of a
      mini-laparotomy when surgery commences, and the wound is stretched and compressed
      throughout the procedure. In addition, it is associated with a more intense
      manipulation of the intraabdominal viscera. All of these factors increase the
      surgical trauma, it is not known whether HALS maintains the minimally invasive
      characteristics of conventional LS. Therefore, we set out to study the
      applicability, immediate clinical outcome, inflammatory response, and cost of
      HALS compared with conventional LS using colectomy as a model. METHODS: We
      performed a prospective randomized trial comparing laparoscopic-assisted
      colectomy with HAL colectomy. The aims of the study were to assess (a)
      perioperative features, including time, advantages, and conversion; (b) the
      patient's immediate clinical response, including recovery of bowel sounds,
      refeeding time, postoperative pain, local and general morbidity, and hospital
      stay; (c) the effect on the inflammatory response, using interleukin-6 (ILG) and
      C-reactive protein (CRP) measurements; (d) oncological issues, including
      intraoperative cytology and features of the specimen; and (d) the relative costs
      of the two procedures. RESULTS: A total of 54 patients were enrolled in the
      study, 27 laparoscopic and 27 HALS. The operative times were similar, but HALS
      was associated with a far lower conversion rate--7% vs 23%. Immediate clinical
      outcomes, oncological features, and costs were similar for the two procedures,
      but HALS was associated with a significantly greater increase in IL6 and CRP than
      the conventional laparoscopic procedure. CONCLUSION: This comparative study shows
      that HALS simplifies difficult intraoperative situations, reducing the need for
      conversion. Although it is a more aggressive procedure, HALS preserves the
      features of a minimally invasive approach, maintains all of the oncological
      features of conventional laparoscopic surgery, and does not increase the cost.
      HALS should therefore be considered as a useful adjunct when difficult situations
      arise during conventional laparoscopic colectomy.

PMID- 11967671
TI  - Simultaneous bilateral laparoscopic inguinal hernia repair: an analysis of 1336
      consecutive cases at a single center.
AB  - BACKGROUND: We compare the use of unilateral and simultaneous bilateral
      laparoscopic hernioplasty [transabdominal preperitoneal patch (TAPP)] METHOD: We
      employed a prospective consecutive single-center trial lasting from April 1993 to
      December 2000. RESULTS: In our study, 5524 consecutive patients underwent 6860
      laparoscopic hernia repairs. The median age in group A (unilateral repair, n =
      4188) was 58 years (16-94 years), and that in group B (simultaneous bilateral
      repair, n = 1336) was 60 years (19-97 years) in (simultaneous bilateral repair, n
      = 1336). Morbidity in group A was 3.2% (135/4188) with a 0.6% reoperation rate
      (24/4188); in group B morbidity was 5.0% (67/1336) with a 1.4% reoperation rate.
      (19/1336). Morbidity and reoperation rates showed no statistically significant
      difference between the two groups in relation to number of repairs in group B.
      After a median 24-month clinical follow-up period (1-84 months) (follow-up rate
      93.1%) 38 recurrences were observed in group A (0.9%) and 17 in group B (0.6%;
      17/2672) (p = 0.2668). Median time off work was 14 days after unilateral (2-63
      days) and 17 days after bilateral repair (3-100 days) (p = 0.1359). Pain levels
      (numerical analogue scale) and incidence of persistent inguinal and scrotal pain
      are not higher after bilateral repair. CONCLUSION: Compared to unilateral repair,
      bilateral simultaneous laparoscopic hernia repair (TAPP) is safe, comfortable for
      patients, and cost-effective, without increased morbidity or recurrence risk.
      Bilateral inguinal hernia is an ideal indication for endoscopic transabdominal
      repair.

PMID- 11967672
TI  - Short-term impact of carbon dioxide, helium, and gasless laparoscopic donor
      nephrectomy on renal function and histomorphology in donor and recipient.
AB  - BACKGROUND: Laparoscopic donor nephrectomy has the potential to increase the
      number of living kidney donations by reducing donor morbidity. However, studies
      have shown that raised intraabdominal pressure can result in transient renal
      dysfunction. Therefore, laparoscopically procured kidneys might be at higher risk
      for suffering a period of ischemia during pneumoperitoneum. The objective of this
      study was to investigate the short-term impact of pneumoperitoneum used for
      laparoscopic donor nephrectomy on renal function and histomorphology in donor and
      recipient. METHODS: EXPERIMENT 1: KIDNEY DONOR: Initially, 36 brown Norway (BN)
      rats were randomized for three procedures: 2 h of carbon dioxide (CO2)
      insufflation (8 mmHg), 2 h of helium insufflation (8 mmHg), and 2 h of gasless
      technique (0 mmHg). After this, a unilateral nephrectomy was performed in all the
      animals. EXPERIMENT 2: RECIPIENT: Subsequently, 36 donor BN rats were subjected
      to a similar insufflation protocol, but after nephrectomy, a syngeneic kidney
      transplantation (BN-BN) was performed. Urine and blood samples were collected on
      postoperative days 1, 3, 7, and 14 for determination of renal function.
      Subsequently, donor and recipient kidneys were removed for histomorphologic and
      immunohistochemical analysis. RESULTS: In both donors and recipients, no
      significant changes in serum creatinine, proteinuria, or glomular filtration were
      detected between the CO2, the helium, and the gasless control groups. In both
      experiments, histologic analysis of Kidney specimens did not show any deleterious
      effects from abdominal gas insufflation. Although kidney grafts exposed to CO2
      showed significantly higher numbers of CD45+ leukocytes 3 days after
      transplantation, immunohistochemical analysis did not show significant
      differences in number of infiltrating cells (CD4, CD8, ED1, OX6, OX62) between
      the two insufflation groups and the gasless control subjects. CONCLUSIONS:
      Abdominal gas insufflation does not have an adverse effect on the renal function
      of the kidney donor 1 week after laparoscopic donor nephrectomy. No differences
      in renal function or histomorphology were detected between syngeneic kidney
      grafts exposed to pneumoperitoneum and gasless control subjects.

PMID- 11967673
TI  - The positive impact of laparoscopic adrenalectomy on complications of adrenal
      surgery.
AB  - BACKGROUND: This study was conducted to determine whether laparoscopic
      adrenalectomy (LA) has had a positive impact on the incidence and nature of
      adrenalectomy-related complications, as compared with the prelaparoscopic era.
      METHODS: All English language reports of patients undergoing either open
      adrenalectomy (OA) or LA from 1980 to 2000 were identified by Medline search.
      Reports were analyzed for the frequency and type of complications, with a minimum
      of 10 cases or studies required for inclusion. Complications were stratified by
      type and/or organ system involved, and groups were compared statistically using
      generalized linear model methods. RESULTS: Complications were tabulated from 50
      studies of LA involving 1,522 patients and 48 studies of OA comprising 2,273
      patients. Among the reports, 22 compared LA and OA within a single institution.
      The total reported complication rate was 25.2% with LA versus 10.9% with OA (p <
      or = 0.0001). The incidence of bleeding complications was higher with LA (4.7%)
      than OA (3.7%) (p < or = 0.0001). As compared with LA, OA had a significantly
      higher incidence of associated organ injury (2.4% vs 0.7%), mainly to the spleen,
      and more wound (6.9% vs 1.4%), pulmonary (5.5% vs 0.9%), cardiac (1.6% vs 0.3%),
      and infectious (5.8% vs 1.6%) complications (p < or = 0.0001). No significant
      differences in gastrointestinal, thromboembolic, or neurologic complications were
      seen. The mortality rate was 0.3% after LA and 0.9% after OA. The difference was
      not significant. CONCLUSIONS: Laparoscopic adrenalectomy has resulted in fewer
      adrenalectomy-related complications than seen historically with OA. Fewer wound
      and pulmonary complications and a reduced incidence of incidental splenectomy are
      primarily responsible for this improved outcome.

PMID- 11967674
TI  - A critical analysis of intraoperative time utilization in laparoscopic
      adrenalectomy.
AB  - BACKGROUND: Time and efficiency analysis is a technique common in industry that
      is being applied to surgical procedures. The aim of this study is to analyze the
      time spent performing the component parts of laparoscopic adrenalectomy by both
      the lateral transabdominal and the posterior retroperitoneal approaches. METHODS:
      Operational videotapes of 33 patients undergoing laparoscopic adrenalectomy (12
      lateral, 21 posterior) were reviewed. The operation was divided into six steps:
      trocar entry, laparoscopic ultrasonography, exposure of the adrenal gland,
      dissection of the adrenal, extraction of specimen, and irrigation-aspiration.
      Time spent for each step and the relation with age, gender, body mass index
      (BMI), tumor size, side, and histology were assessed using Student's t-test,
      Pearson correlation, and regression analysis. RESULTS: Although tumor size was
      larger in the lateral compared to the posterior approach (5.5 vs 2.5 cm, p <
      0.001), there was no difference between the groups regarding total operating time
      (116.1 vs 112.8 min). Most of the operating time was spent on dissection of the
      adrenal gland with both techniques (lateral, 60%; posterior, 66%). Exposure of
      the adrenal gland was longer in the lateral compared to the posterior approach
      (15.1 vs 5.8 min, respectively; p < 0.05). In the transabdominal technique, this
      step was longer on the right side than on the left (18.9 vs 11.4 min,
      respectively; p < 0.05). In the lateral approach, dissection time was dependent
      on tumor size (r = 0.90, p < 0.05) but not on BMI, whereas in the posterior
      approach both tumor size and BMI were positively correlated (r = 0.56 and r =
      0.64, respectively). CONCLUSIONS: To our knowledge, this is the first study to
      apply time analysis techniques to laparoscopic adrenal surgery. Understanding the
      variables that affect operative time may influence the choice of the surgical
      approach in a given patient. This study also suggests that efforts to improve
      operative efficiency are best directed at the dissection of the adrenal.

PMID- 11967675
TI  - Outcome of esophageal adenocarcinoma detected during endoscopic biopsy
      surveillance for Barrett's esophagus.
AB  - BACKGROUND: In an attempt to reduce mortality from esophageal adenocarcinoma, it
      has been recommended to enroll patients with Barrett's esophagus in endoscopic
      surveillance programs in order to detect malignant degeneration at an early and
      possibly curable stage. The aim of this study was to assess the impact of
      endoscopic biopsy surveillance on outcome of Barrett's adenocarcinoma. METHODS:
      Between November 1992 and June 2000, 312 patients with histologically proven
      esophageal adenocarcinoma were referred to our department. Ninety-seven of these
      patients had Barrett's adenocarcinoma. In 12 (12.2%) patients, cancer was
      discovered during endoscopic surveillance for Barrett's metaplasia. RESULTS: The
      prevalence of gastroesophageal reflux disease in the Barrett's group was 38.8%
      versus 8% (p < 0.01) in non-Barrett's patients. In the surveyed group, there were
      9 (75%) early stage tumors (Tis-1/N0) versus 9 (10.6%, p < 0.01) in the
      nonsurveyed patients. Three of 5 surveyed patients operated on for high-grade
      dysplasia proved to have invasive carcinoma in the esophagectomy specimen. All
      surveyed patients were alive at a median follow-up of 48 months; the median
      survival in the nonsurveyed group was 24 +/- 3 months (p < 0.01). CONCLUSION:
      Endoscopic surveillance of Barrett's esophagus provides early detection of
      malignant degeneration and a better long-term survival than in nonsurveyed
      patients.

PMID- 11967676
TI  - Ergonomic principles of task alignment, visual display, and direction of
      execution of laparoscopic bowel suturing.
AB  - BACKGROUND: Laparoscopic suturing is technically a demanding skill in
      laparoscopic surgery. Ergonomic experimental studies provide objective
      information on the important factors and variables that govern optimal endoscopic
      suturing. Our objective was to determine the optimum physical alignment, visual
      display, and direction of intracorporeal laparoscopic bowel suturing using
      infrared motion analysis and telemetric electromyography (EMG) systems. METHODS:
      Ten surgeons participated in the study; each sutured 50-mm porcine small bowel
      enterotomies toward and away from the surgeon in the vertical and horizontal
      bowel plane with either isoplanar (image display corresponds with actual lie of
      the bowel) or nonisoplanar (bowel displayed horizontally but mounted vertically
      in the trainer and vice versa) display. The end points were the placement error
      score, execution time, leakage pressure, motion analysis, and telemetric EMG
      parameters of the surgeon's dominant upper limb. RESULTS: Suturing was
      demonstrably easier in the vertical than in the horizontal plane, resulting in a
      better task quality (placement error score, p < 0.0001; leakage pressure, p <
      0.005) and shorter execution time (p < 0.05). Nonisoplanar display of the
      surgical anatomy degrades performance in terms of both task efficiency and task
      quality. On motion analysis, a wider angle of excursion and lower angular
      velocity were observed during the vertical suturing with isoplaner display.
      Compared to horizontal suturing, supination at the wrist was significantly
      greater during vertical than horizontal suturing (p < 0.05). Within each category
      (vertical vs horizontal suturing), the direction of suturing (toward/away from
      the surgeon) did not influence the extent of pronation/ supination at the wrist.
      In line with the degraded performance, significantly more muscle work was
      expended during horizontal suturing. This affected the forearm flexors (p <
      0.05), arm flexors and extensors (p < 0.005 and p < 0.05, respectively), and
      deltoid muscles (p < 0.005) and was accompanied by significantly more fatigue in
      the related muscles. Small bowel enterotomies sutured toward the surgeon in both
      the vertical and the horizontal planes exhibited less placement error score than
      when sutured away from the surgeon, with no significant difference in the motion
      analysis and EMG parameters. CONCLUSIONS: Optimal laparoscopic suturing (better
      task quality and reduced execution time) is achieved with vertical suturing
      toward the surgeon with isoplanar monitor display of the operative field. The
      poorer task performance observed during horizontal suturing is accompanied by
      more muscle work and fatigue, and it is not improved by monitor display of the
      enterotomy in the vertical plane.

PMID- 11967678
TI  - Sequence and task analysis of instrument use in common laparoscopic procedures.
AB  - BACKGROUND: In the area of instrument evaluation, one aspect that still requires
      objective assessment is the dynamics of instrument maneuver and exchange. If we
      could gain a better understanding of these phenomena, we could improve the design
      of the instruments themselves. METHODS: A total of 29 laparoscopic procedures
      were videotaped and reviewed using time motion analysis. Instrument
      multifunctionality was determined using a standardized list of laparoscopic
      maneuvers. State transition diagrams were utilized to document the sequence of
      instrument exchanges. RESULTS: The curved dissector, atraumatic grasper, and
      cautery scissors were identified as the most multifunctional instruments; each
      was able to perform five distinct maneuvers. Instrument sequences were found to
      consist of a three-part dissect --> clip --> cut cycle and a two-part dissect -->
      suction cycle of instrument exchange. CONCLUSION: This study demonstrated that
      laparoscopic instruments are often used to perform a variety of maneuvers in
      addition to their primary function. Furthermore, there are common patterns in
      instrument exchange that provide a potential source of design parameters for
      improved surgical efficiency.

PMID- 11967679
TI  - Ondansetron in the prevention of postoperative nausea and vomiting after
      laparoscopic cholecystectomy: a prospective randomized study.
AB  - BACKGROUND: There is an increased incidence of postoperative nausea and vomiting
      (PONV) after laparoscopic cholecystectomy. The aim of the study was to evaluate
      the efficacy of intravenous ondansetron, a 5-HT anatagonist, for prevention from
      PONV after laparoscopic cholecystectomy. METHODS: Sixty-eight patients were
      entered into the study. Thirty-six patients were randomized to receive a single
      intravenous dose of 4 mg of ondansetron before extubation. Thirty-two patients
      received no prophylaxis. There were no differences in terms of sex ratio, age,
      ASA status, and duration of operation between the two study groups. Patients were
      interviewed by an independent observer to assess the postoperative pain and
      nausea using visual analog score. Patients' satisfaction scores to the procedure
      were measured. RESULTS: There was no complication in the series. Pain scores at 2
      and 24 h after operation and analgesics consumption were not different between
      the two groups. For the patients who received ondansetron, the mean (SD) nausea
      score at 2 and 24 h was 1.5 (1.2) and 1.4 (1.4), respectively. The score for the
      control group was 1.4 (1.0) and 1.2 (0.5), respectively. There was also no
      difference in episodes of vomiting and usage of antiemetics between the two
      groups. Both groups were equally satisfied with the procedures. CONCLUSION:
      Routine use of ondansetron does not reduce the incidence of postoperative nausea
      and vomiting after laparoscopic cholecystectomy.

PMID- 11967677
TI  - Outcome of laparoscopic splenectomy based on hematologic indication.
AB  - BACKGROUND: Laparoscopic splenectomy is the procedure of choice for elective
      splenectomy at the Cleveland Clinic Foundation. Although the literature clearly
      documents the technical feasibility and safety of laparoscopic splenectomy,
      little data exists concerning the results of this procedure based on the
      hematologic indication for splenectomy. We sought to examine the clinical
      experience with laparoscopic splenectomy in a single institution, with particular
      attention to morbidity and clinical outcomes based on hematologic disease
      process. METHODS: This study retrospectively reviewed a consecutive series of
      laparoscopic splenectomies performed for nontraumatic, splenic pathology at the
      Cleveland Clinic Foundation from August 1995 to January 2001. Patient
      demographics, operative indications, morbidity, mortality, and clinical outcome
      were evaluated. Hematologic diagnostic groups were compared using Fisher's exact
      tests and Wilcoxon rank-sum tests. RESULTS: A total of 147 laparoscopic
      splenectomies were performed. Seven patients (5%) required conversion to open
      splenectomy. Indications for splenectomy included idiopathic thrombocytopenic
      purpura (ITP) in 65 patients, hematologic malignancy in 43 patients, autoimmune
      hemolytic anemia (AIHA) in 9 patients, thrombotic thrombocytopenic purpura (TTP)
      in 9 patients, splenomegaly in 5 patients, splenic cyst in 4 patients, splenic
      abscess in 3 patients, hereditary spherocytosis in 2 patients, splenic artery
      aneurysm in 2 patients, Felty's syndrome in 1 patient, myelofibrosis in 1
      patient, and other in 3 patients. Accessory spleens were identified in 20
      patients (14%). Postoperative complications occurred in 23 (16%) patients.
      Patients with ITP had significantly shorter operation times (134 vs 163 min; p =
      0.001), decreased estimated blood loss (126 vs 307 ml; p = 0.001), decreased
      length of hospital stay (2.8 vs 4.6 days; p < 0.001), and less chance of
      conversion (0 vs 7; p = 0.02) than patients with any other diagnosis. A mean
      follow-up period of 20 +/- 14 months showed an 85% rate of remission for ITP, 89%
      for TTP, and 89% for AIHA. Patients with malignant disease had significantly
      larger spleens (822 vs 313 g; p < 0.001), more estimated blood loss (380 vs 168
      ml; p = 0.04), and longer operative times (170 vs 142 min; p = 0.009), as
      compared patients treated for benign disease. However, the length of hospital
      stay (4.3 vs 3.6 days; p = 0.06) and complication rates (19% vs 14%; p = 0.08)
      were not significantly different between the two groups. CONCLUSIONS: When
      performed for ITP, laparoscopic splenectomy resulted in shorter operations,
      minimal blood loss, earlier discharge, no conversions, and excellent remission
      rates, as compared with other hematologic indications. Despite larger spleens,
      more blood loss, and longer operations in patients with hematologic malignancies,
      morbidity and length of hospital stay still were similar to those associated with
      benign indications for laparoscopic splenectomy. In conclusion, laparoscopic
      splenectomy is safe and efficacious for a multitude of benign and malignant
      hematologic indications, and our data compares favorably to those for open
      series.

PMID- 11967681
TI  - Hematogenous spread as a mechanism for the generation of abdominal wound
      metastases following laparoscopy.
AB  - BACKGROUND: We designed this study to determine whether hematogenous spread has a
      role in the etiology of port site metastases following laparoscopic surgery.
      METHODS: The study design had two parts. In experiment 1, two groups (n = 30) of
      male Dark Agouti rats were studied. Under general anesthesia, the first group (20
      rats) underwent 15 mins of laparoscopic insufflation, followed by an injection of
      a suspension of 105 Dark Agouti mammary adenocarcinoma (DAMA) cells into the
      internal jugular vein and a further 15-mins period of insufflation. The
      laparoscopic ports were then removed, and the wounds were closed and marked. In
      the second group (n = 10), the procedure was identical except that a 2.5-cm
      midline laparotomy was performed 15 mins after the commencement of anesthesia and
      insufflation was not used. The laparotomy was closed in two layers. In experiment
      2, one group (n = 4) was studied. The study protocol was identical to the first
      laparoscopic group except that a larger number of 106 DAMA cells were injected.
      All rats in both experiments were killed 15 days later, and the injection site,
      laparoscopy wounds, and laparotomy wound were examined histologically by a
      blinded histopathologist. RESULTS: In experiment 1, one port site tumor was
      detected in the laparoscopic group and no wound metastases were found in the
      laparotomy group. Postoperative weight loss was significantly less in the
      laparoscopic group (p < 0.001). In experiment 2, no port site metastases were
      detected. CONCLUSION: Although hematogenous spread is a possible mechanism in the
      development of port site metastases, judging from the low number of port site
      metastases in this study as compared to previous reports using this tumor model,
      this mechanism is unlikely to be a major contributor to the problem of wound
      metastasis following laparoscopy.

PMID- 11967680
TI  - Peritoneal closure reduces port site metastases: results of an experiment in a
      rat ovarian cancer model.
AB  - BACKGROUND: The arm of this study was to assess the role of peritoneal closure in
      the prevention of port site metastasis after carbon dioxide (CO2) CO2
      pneumoperitoneum. METHODS: We developed a xenograft ovarian cancer model by
      intraperitoneal injection of 27 106 IGR-OV1 line cells in nude rats Seven days
      after the inoculation, the animals underwent a CO2 pneumoperitoneum. At the end
      of the procedure, port sites were randomly closed either with suture of
      peritoneum (n = 14, group A) or without suture of peritoneum (n = 12, group B).
      The rats were killed 7 days after surgery and their port site scars were
      resected. Tumor implantation was assessed by a pathologist who was blinded to the
      type of wound closure. RESULTS: The animals in group B were significantly more
      likely to have at least one port site metastasis frequent (seven of 12, or 58.3%)
      than those in group A (two of 14, or (14.3%) (p = 0.037). Port sites with
      metastases were seen more frequently in group B (eight of 24, or (33.3%) than in
      group A (three of 28, or 10.7%) (p = 0.046). CONCLUSIONS: Our results shows that
      peritoneum closure decreases the risk of port site metastasis.

PMID- 11967682
TI  - Functional anatomy of the papilla Vateri: biomechanical aspects and impact of
      difficult endoscopic intubation.
AB  - BACKGROUND: Problems with intubation of the ampulla Vateri during diagnostic and
      therapeutic endoscopic maneuvers are a well-known feature. The ampulla Vateri was
      analyzed three-dimensionally to determine whether these difficulties have a
      structural background. METHODS: Thirty-five human greater duodenal papillae were
      examined by light and scanning electron microscopy as well as
      immunohistochemically. RESULTS: Histologically, highly vascularized finger-like
      mucosal folds project far into the lumen of the ampulla Vateri. The excretory
      ducts of seromucous glands containing many lysozyme-secreting Paneth cells open
      close to the base of the mucosal folds. Scanning electron microscopy revealed
      large mucosal folds inside the ampulla that continued into the pancreatic and
      bile duct, comparable to valves arranged in a row. CONCLUSIONS: Mucosal folds
      form pocket-like valves in the lumen of the ampulla Vateri. They allow a
      unidirectional flow of secretions into the duodenum and prevent reflux from the
      duodenum into the ampulla Vateri. Subepithelial mucous gland secretions
      functionally clean the valvular crypts and protect the epithelium. The
      arrangement of pocket-like mucosal folds may explain endoscopic difficulties
      experienced when attempting to penetrate the papilla of Vater during endoscopic
      retrograde cholangiopancreaticographic procedures.

PMID- 11967683
TI  - Endoscopic-assisted subcutaneous mastectomy and axillary dissection with
      immediate mammary prosthesis reconstruction for early breast cancer.
AB  - BACKGROUND: Endoscopic surgery has been applied successfully in breast lump
      excision, breast augmentation, subcutaneous mastectomy for gynecomastia, and
      axillary dissection. Since subcutaneous mastectomy has been proven to be
      oncologically safe for early breast cancer, we have sought to develop a
      reproducible minimally invasive endoscopic-assisted technique to address this
      condition. METHODS: Between December 1998 and May 1999, endoscopic-assisted
      subcutaneous mastectomy and axillary dissection with immediate reconstruction
      using a mammary prosthesis was performed in nine patients with early breast
      cancer at the Prince of Wales Hospital, Hong Kong. A 5-cm skin incision was made
      along the line of the lowest axillary skin crease. Dissection was continued down
      to the lateral border of the pectoralis major muscle. A subpectoral pocket was
      gently created by an endoscopic breast dissector. The endoscopic breast retractor
      and 10-mm/30 degrees scope were introduced into the subpectoral pocket, and
      further dissection was carried out using a 7-in harmonic scalpel under endoscopic
      vision down to a level 1 cm caudal to the inframammary fold. This subpectoral
      space was used for the insertion of the mammary prosthesis later on. Endoscopic
      assisted subcutaneous mastectomy was performed afterward. Combined level I and
      level II axillary dissection was carried out via the same incision under direct
      vision. RESULTS: Apart from minor skin flap bruises in our first two patients,
      there were no major complications. Histological examination of all the specimens
      showed clear margins. Postoperative radiotherapy and chemotherapy were given in
      the usual manner. All patients were satisfied with the reconstructive outcome.
      CONCLUSIONS: We have described a novel endoscopic technique for subcutaneous
      mastectomy with immediate mammary prosthesis reconstruction in treating early
      breast cancer patient. This technique can minimize skin incision, reduce blood
      loss, and improve reconstructive outcome. It is easy to learn and well accepted
      by patients.

PMID- 11967684
TI  - Experience with endoscopic axillary lymphadenectomy using needlescopic
      instruments in patients with breast cancer: a preliminary report.
AB  - BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of
      endoscopic axillary lymphadenectomy using needlescopic instruments in patients
      with breast cancer. METHODS: Five patients with breast cancer were treated by
      partial mastectomy and endoscopic axillary lymphadenectomy. We evaluated the
      results of the surgical procedure and the postoperative course. RESULTS: In all
      the patients, endoscopic axillary lymphadenectomy was performed successfully. The
      mean duration of the operation was 105.4 min, the mean blood loss 19.4 ml, and
      the mean number of dissected axillary lymph nodes 13. There were no intra- or
      postoperative complications. The mean amount of lymphorrhea was 131.2 ml, and the
      mean duration of drainage was 3.6 days. No postoperative analgesics were
      administered. CONCLUSIONS: Endoscopic axillary lymphadenectomy can be performed
      safely with needlescopic instruments, but further study is needed to establish
      this technique.

PMID- 11967685
TI  - Gastric outlet obstruction secondary to pancreatic cancer: surgical vs endoscopic
      palliation.
AB  - BACKGROUND: Gastric outlet obstruction in patients with pancreatic cancer has a
      grim prognosis. Open surgical bypass is associated with high morbidity, whereas
      endoscopic duodenal stenting appears to provide better palliation. METHODS: We
      reviewed the medical records of patients with gastric outlet obstruction
      secondary to pancreatic carcinoma who were admitted to our clinic between 1
      October 1988, and 30 September 1998. The data included stage of disease, American
      Society of Anesthesiologists (ASA) class, surgical interventions, complications,
      and survival. RESULTS: A total of 250 patients with pancreatic cancer were
      identified. Twenty-five of them (10%) had gastric outlet obstruction. Of these
      25, 17 were treated with gastrojejunostomy, six had duodenal stenting
      (Wallstent), and two were resectable. There was no significant difference between
      the gastrojejunostomy group and the duodenal stenting group in ASA class or stage
      of disease. For the gastrojejunostomy group, median survival was 64 days (range,
      15-167) and postoperative stay in hospital was 15 days (range, 8-39). For the
      duodenal stenting group, median survival was 110.5 days (range, 42-212) and
      postoperative stay was 4 days (range, 2-6). Ten patients (58.8%) in the
      gastrojejunostomy group had delayed gastric emptying. All of the patients in the
      duodenal stenting group were able to tolerate a soft diet the day after stent
      placement. Thirty-day mortality in the gastrojejunostomy group was 17.64%; in the
      duodenal stenting group, it was 0. CONCLUSION: In pancreatic carcinoma patients
      with gastric outlet obstruction, duodenal stenting results in an earlier
      discharge from hospital and possibly improved survival.

PMID- 11967686
TI  - Systemic acute-phase response after laparoscopic and open cholecystectomy.
AB  - BACKGROUND: Cytokines are the main mediators of inflammation and the response to
      trauma. The purpose of this study was to compare variations in cytokine levels
      following laparoscopic cholecystectomy (LC) and mini-laparotomy cholecystectomy
      (OC), since these two types of operations were considered to be a unique model
      for examining the role of local tissue injury in postoperative inflammatory
      reactions. METHODS: A total of 40 patients were studied. Eighteen of them
      underwent LC; the remaining 22 were operated on using the open technique.
      Systemic concentrations of interleukin-6 (IL-6), interleukin-1 (IL-1), tumor
      necrosis factor (TNF), and C-reactive protein (CRP) were measured before and
      after the operation. In addition, we compared pre- and postoperative white blood
      cell (WBC) counts, postoperative body temperature, and length of postoperative
      hospitalization. RESULTS: There was no difference between the two groups in IL-1
      and TNF response. The rise in plasma IL-6 levels (18.86 +/- 9.61 vs 5.00 +/- 0.0
      pg/ml, p < 0.0001) and CRP (8.40 +/- 5.81 vs 1.43 +/- 1.30 mg/dl, p < 0.001) were
      more marked after open cholecystectomy than after the laparoscopic procedure.
      There was no correlation between serum CRP concentrations and the other
      postoperative parameters. CONCLUSION: The magnitude of the acute-phase response
      was less pronounced following laparoscopic cholecystectomy, consistent with a
      reduction in tissue trauma.

PMID- 11967687
TI  - An experimental model of gastroschisis using fetoendoscopy: preliminary results
      and technical considerations.
AB  - BACKGROUND: The aim of this study was to show the feasibility of an experimental
      model of gastroschisis using fetoendoscopic surgery on sheep fetuses, and also to
      perform amnioinfusion until delivery using an in-dwelling intraamniotic catheter.
      METHODS: We analyzed the data from 18 pregnant ewes having 26 fetuses, which
      underwent surgery at 80 days of gestation (full term, 145 days). The fetendo
      technique was used to create a gastroschisis in 15 fetuses. The fetal abdominal
      wall was opened on the left side of the cord using scissors. The omentum and the
      intestinal loops were eviscerated using atraumatic forceps. Eleven fetuses were
      used as a control group. Twenty-one fetuses underwent amnioinfusion; a simple
      exteriorized catheter was used in seven cases and an intraamniotic catheter with
      an implantable port was used in the other 14. All ewes and fetuses were killed at
      the end of the experiment by an intravenous injection of pentotal; thereafter,
      the fetuses underwent necropsy. RESULTS: Twelve fetuses died and 14 survived
      (53.8%); seven of the 15 that underwent gastroschisis survived (46.7%). An
      amniotic infection occurred in nine fetuses (34.6%); of these, six died and three
      that were administered antibiotics survived. CONCLUSIONS: Our experience shows
      that this experimental model of gastroschisis is feasible and reproducible, and
      that a repeated amnioinfusion can be performed with an in-dwelling catheter in
      pregnant ewes. The use of an implantable port is safer than a simple exteriorized
      catheter.

PMID- 11967688
TI  - Endoscopic total parathyroidectomy by the anterior chest approach for renal
      hyperparathyroidism.
AB  - BACKGROUND: During the past 3 years, minimally invasive procedures have been
      adopted for the surgical treatment of primary hyperparathyroidism, and we have
      tried to perform endoscopic total parathyroidectomy for renal
      hyperparathyroidism. METHODS: Five 5-mm trocars were inserted through the skin of
      the anterior chest under a general anesthesia. Carbon dioxide was then
      insufflated up to 4 mmHg, and the endoscopic surgery was performed. RESULTS:
      Endoscopic procedure was successfully performed in five patients. The mean
      duration of total parathyroidectomies was 236 min. No evidence of injury to the
      recurrent laryngeal nerve was observed in any cases. At follow-up, the serum
      calcium and parathyroid hormone levels had returned to within the normal range in
      all patients. Postoperative cosmetic status was excellent. CONCLUSION: We believe
      that endoscopic total parathyroidectomy by the anterior chest approach will find
      a role in the treatment of renal hyperparathyroidism.

PMID- 11967689
TI  - Transitions in laparoscopic cholecystectomy: the impact of ambulatory surgery.
AB  - BACKGROUND: Ambulatory laparoscopic cholecystectomy is a common practice in the
      United States, but its development remains slow in most other countries. The
      objective of the current study was to report the impact of ambulatory surgery on
      the practice of laparoscopic cholecystectomy in a major teaching hospital since
      the inception of the service. METHODS: The hospital database of patients who
      underwent cholecystectomies for benign hepatobiliary pathologies was reviewed
      between January 1993 and December 1999. Changes in the practice of laparoscopic
      cholecystectomy and the length of hospital stay were analyzed. Clinical
      characteristics of the ambulatory and inpatient groups were compared. RESULTS: Of
      2,891 laparoscopic cholecystectomies involved in the current study, 888 (31%)
      were performed as day cases, and 2,003 (69%) were performed as inpatient
      laparoscopic cholecystectomies. The annual number of ambulatory laparoscopic
      cholecystectomies increased from 3 (0.6%) in 1993 to 212 (48%) in 1997. This was
      followed by a plateau in the next 3 years. The ambulatory group comprised a
      significantly higher prevalence of young women (87%) who underwent surgery mainly
      for biliary colic (88%). CONCLUSIONS: The current study demonstrated a net trend
      toward ambulatory laparoscopic cholecystectomy and a shorter length of hospital
      stay. Almost half of our patients with gallstone disease currently are using the
      ambulatory laparoscopic cholecystectomy service, with young women constituting
      the majority. We predict that ambulatory laparoscopic cholecystectomy heralds the
      wave of the future, and our experience may serve as a blueprint for other
      institutions wishing to embark on this journey.

PMID- 11967690
TI  - Availability of lobe-selective bronchial blockade for video-assisted thoracic
      surgery: an initial experience with three cases.
AB  - BACKGROUND: Stable oxygenation and sufficient collapse of the lung are essential
      for video-assisted thoracic surgery (VATS). We performed the lobe-selective lung
      collapse technique with VATS for patients who had deteriorated lung function.
      METHODS AND RESULTS: CASE 1: A 75-year-old man who had undergone thoracoplasty
      showed spontaneous pneumothoraces in the contralateral side. Bullae were stapled
      successfully under complete isolation and collapse of diseased lobe. CASE 2: A 57
      year-old woman who had undergone left lower lobectomy for lung cancer presented
      with another lung cancer in the right lower lobe. The right lower lobe bronchus
      was closed selectively, and basal segmentectomy was performed. CASE 3: A 60-year
      old woman who had lost left lung function presented with right-side spontaneous
      pneumothoraces. The right upper lobe was collapsed selectively, and bullectomy
      was performed. CONCLUSION: Lobe-selective bronchial blockade may be beneficial
      when VATS is performed for selected patients with deteriorated lung function.

PMID- 11967691
TI  - Increased insufflation pressure enhances the development of liver metastasis in a
      mouse laparoscopy model: possible mechanisms.
AB  - BACKGROUND: The effect of different insufflation pressures and durations of CO2
      pneumoperitoneum on the growth of liver metastasis was investigated in a mouse
      model. The possible mechanisms involved in the pressure-related enhancement of
      liver metastasis were also examined. METHODS: Mice inoculated intraportally with
      colon 26 cells underwent CO2 pneumoperitoneum at different pressures (5,10, or 15
      mmHg) for 30 or 60 min, or received no treatment other than tumor cell
      inoculation (control). The subsequent growth of liver metastases was examined.
      Mice injected intraportally with 111In-oxine-labeled colon 26 cells underwent
      pneumoperitoneum at three different pressures or served as controls. The
      radioactivity of the liver was determined to evaluate tumor accumulation in the
      liver. Mice received pneumoperitoneum at three different pressures or received
      trocar placement alone. Changes in plasma interleukin-6 levels were determined.
      RESULTS: The growth of liver metastases on day 14 was influenced by increased
      insufflation pressures (p < 0.05) rather than the prolonged duration of
      pneumoperitoneum without significant interaction. The 15-mmHg pneumoperitoneum
      group showed a higher (p < 0.05) accumulation of radioactivity in the liver
      compared with the 5-mmHg pneumoperitoneum group and controls. Pneumoperitoneum
      groups with 5 and 10 mmHg showed higher (p < 0.05) peak levels of IL-6 compared
      with controls. CONCLUSIONS: An elevated insufflation pressure plays an important
      role in the enhancement of liver metastases, and this pressure-related adverse
      effect may be partly relevant to facilitating accumulation of tumor cells in the
      liver.

PMID- 11967692
TI  - Laparoscopic intracorporeal ultrasound versus fluoroscopic intraoperative
      cholangiography: after the learning curve.
AB  - BACKGROUND: The purpose of this study was to compare the results of laparoscopic
      intracorporeal ultrasound (LICU) to those of fluoroscopic intraoperative
      cholangiography (FIOC) during laparoscopic cholecystectomy (LC) after the initial
      learning curve for LICU. METHODS: Data were prospectively collected on patients
      undergoing LC. A consecutive series of 394 LICU patients was compared to a
      consecutive series of 400 FIOC patients when each imaging procedure was
      preferentially performed. Patients during the transition period, including the
      first 100 LICU patients, were excluded. RESULTS: Demographics and preoperative
      diagnoses were similar in the two groups. Excluding those who were converted to
      open cholecystectomy and those in whom an imaging exam was not attempted, FIOC
      was successful in 361 of 374 (97%) patients and LICU was successful in 377 of 380
      (99%) patients (p < 0.03). The mean times (+/-SEM) to complete FIOC and LICU were
      16.0 (+/-0.5) min and 5.1 (+/-0.1) min (p < 0.0001), respectively,
      Choledocholithiasis was detected in 25 patients (7%) undergoing FIOC and in 39
      patients (10%) undergoing LICU (p = 0.1). During LICU the common bile duct was
      visualized in continuity from the cystic duct to ampulla in 90% of cases. The
      common bile duct could not be completely visualized in continuity at the middle
      or distal portion of the common bile duct in 5% and 6% of LICU cases,
      respectively. One LICU patient (0.3%) with an incompletely visualized duct had a
      suspected stone confirmed by postoperative endoscopic retrograde
      cholangiopancreaticography (ERCP). One patient with negative FIOC (0.3%) had a
      retained stone treated by postoperative ERCP. CONCLUSION: LICU is safe and
      accurate, and it permits a more rapid evaluation of bile duct stones than FIOC
      during laparoscopic cholecystectomy. The false-negative rate of both imaging
      techniques is less than 1%.

PMID- 11967693
TI  - Sealing of cystic duct with bipolar electrocoagulation.
AB  - BACKGROUND: The cystic duct leakage rate is still high. The aim of this study was
      to evaluate an alternative technique for securing the cystic duct using the
      Ligasure vessel sealing system. METHODS: Eight pigs were included in this pilot
      study. We performed a cholecystectomy, using the Ligasure system to sealing the
      cystic duct and artery. The pigs were killed 8 days after operation, and
      specimens of the cystic duct and common bile duct were removed for pathologic
      examination. RESULTS: There were no clinical complications other than two
      superficial wound infections. The sealing of the cystic duct and artery were both
      macroscopically and microscopically 100% sufficient. The maximum extension of the
      coagulative process in the sealed ducts was 0.25 mm on each side of the sealed
      area. CONCLUSIONS: The Ligasure system seems promising for securing the cystic
      duct and artery during cholecystectomy. Future studies should evaluate safety
      with this technique on a larger scale.

PMID- 11967694
TI  - Laparoscopic repair of incisional hernia: a retrospective study of 159 patients.
AB  - BACKGROUND: In this long-term retrospective study, a laparoscopic technique was
      used for incisional hernia repair. METHODS: Over a 6-year period, we performed
      laparoscopic repairs with prosthetic mesh in 159 patients suffering from
      incisional hernia. Morbidity factors were noted and operative data were
      collected. In addition, early and long-term complications and recurrences were
      analyzed. RESULTS: There were no deaths as a result of the procedure. In 21
      patients (13.8%), the operation was converted to an open procedure. Small bowel
      perforation occurred in three patients (1.9%). Mean hospital stay was 3.5 days.
      Early complications occurred in 61 patients (44%). The mean follow-up time was 49
      months. There were no infections of the prosthetic mesh. Residual abdominal pain
      was reported in 31 patients (26%). Bowel obstructions requiring resection were
      found in two patients (1%), and hernia recurrence was observed in 19 patients
      (15.7%). CONCLUSIONS: Laparoscopic herniorraphy is a promising technique with all
      the advantages of minimal-invasive surgery. Nevertheless, close attention needs
      to be paid to the choice of the hernia and mesh size and to the fixing of the
      mesh.

PMID- 11967696
TI  - Thoracoscopic surgery for pneumothorax in older patients.
AB  - BACKGROUND: Secondary pneumothorax is more common in older pneumothorax patients.
      Therefore, we set out to investigate the usefulness of thoracoscopic surgery in
      this group. METHODS: A total of 59 operations were performed on patients aged >
      or = 50 years, with the goal of excising only the lesions responsible for air
      leaks by using the minimum degree of dissection. If the patients were found to
      have numerous bullae, the lesions responsible were identified by pleurography.
      The duration of chest tube drainage, hospital stay, and recurrence were assessed.
      RESULTS: The air leaks stopped and all patients were discharged without drains.
      Postoperative drainage time was 3.8 +/- 3.0 days. Postoperative hospital stay was
      10.8 +/- 9.2 days. Six patients died of other diseases, but there was only one
      recurrence of pneumothorax. CONCLUSION: We consider video-assisted thoracic
      surgery (VATS), with the goal of excising only the lesions responsible for air
      leaks, to be particularly efficacious in older pneumothorax patients.

PMID- 11967695
TI  - Ultrasound-guided interventional procedures of the liver during laparoscopy:
      technical considerations.
AB  - BACKGROUND: The increased application of laparoscopy to oncological cases has
      also expanded the applications of laparoscopic ultrasound (LUS). LUS-guided
      interventional procedures are often used for the staging of neoplastic disease.
      However, considerable expertise is required to perform the US-guided maneuvers.
      METHODS: Based on our 7-year experience with laparoscopic ultrasound, we discuss
      a number of technical and practical aspects related to the performance of
      interventional procedures during LUS of the liver. RESULTS: We performed 146
      laparoscopic ultrasound exams in patients with neoplastic diseases. In all, 244
      liver lesions were biopsied and 151 needle placements were made to perform
      radiofrequency ablation or ethanol injection. We discuss our choice of
      laparoscopic equipment and type of needle required (whether for biopsies or for
      interventional procedures). We also describe the technical characteristics of
      ultrasound probes and equipment, the correct approach to the patient, and the
      method that we employ to identify and then puncture the target lesion.
      CONCLUSION: The proper technique for interventional procedures during
      laparoscopic ultrasound can be mastered relatively quickly by a surgeon who is
      already familiar with traditional ultrasound techniques.

PMID- 11967697
TI  - Laparoscopic repair of an extrahiatal hernia caused by congenital dysplasia: a
      case report.
AB  - A 40-year-old woman with complaints of relapse in the upper abdomen and dysphagia
      was referred for laparascopic hiatal hernia repair. Chest radiograph, barium
      swallow, and upper endoscopy revealed a paraesophageal hernia. Esophageal
      manometry and 24-h-pH study showed no pathological findings. A laparoscopic
      gastropexy was planned. Intraoperatively, in contradiction to the preoperative
      findings, an extrahiatal hernia containing most of the stomach was found. After
      resection of the hernia sac, the beating heart without covering pericardium was
      seen. These findings were confirmed by an additional thoracoscopy at the end of
      the operation. The defect was closed by direct suturing. The postoperative course
      and 2-month follow-up were uneventful. The resected parts of the hernia sac
      showed an embryonic and dysgenetic etiology. This rare malformation has been
      reported in combination with complex syndromes, which appear with serious
      clinical and morphological signs in the neonatal period. In adults, the
      pericardial aplasia can be observed during diagnostic or surgical interventions.
      In these patients, complaints are usually not caused by the malformation but may
      be due to the occasional herniation of abdominal organs. We consider laparoscopic
      repair to be a gentle and safe procedure for the treatment of extrahiatal
      hernias.

PMID- 11967698
TI  - Laparoscopy in a case of pediatric blunt abdominal trauma.
AB  - The use of laparoscopy in the assessment and treatment of blunt abdominal trauma
      has been reported for both adults and children. With increasing surgical
      experience and improvements in equipment, an expanding range of therapeutic
      interventions is available. The management of a 7-year-old boy who sustained
      blunt abdominal trauma during a fall from a bicycle is described. He was
      hemodynamically stable, but his abdomen remained tender, with guarding in the
      right upper quadrant. Serial ultrasound scans showed a thick-walled gallbladder
      and increasing intraabdominal fluid. Laparoscopy was used both as a diagnostic
      tool, and then as a therapeutic method. Diagnostic laparoscopy showed a ruptured
      gallbladder treated by laparoscopic cholecystectomy. A 3-cm grade 1 liver
      laceration also was identified, which required no intervention. Free bile was
      aspirated and the peritoneal cavity thoroughly lavaged. The child made a rapid
      postoperative recovery. The ultimate aim in the management of blunt trauma is to
      avoid unnecessary laparotomy while preventing undue delay in the detection of
      significant intraabdominal pathology. Computed tomography scanning, ultrasound
      scanning, and diagnostic peritoneal lavage all have strengths for detecting
      different injury types, but they also have a low specificity in determining the
      need for laparotomy. The advantages and limitations of laparoscopy in
      hemodynamically stable children who have sustained injuries from blunt trauma are
      discussed. The authors recommend laparoscopy in experienced hands as an
      additional tool for the optimal management of selected trauma cases.

PMID- 11967699
TI  - Planned totally extraperitoneal laparoscopic Spigelian hernia repair.
AB  - A Spigelian hernia is a congenital defect in the tranversus aponeurosis fascia.
      Traditionally, an open anterior hernioplasty was used to repair these defects.
      Recently, laparoscopic approaches have been described. This report describes the
      first application of the totally extraperitoneal laparoscopic approach to a
      planned repair of a Spigelian hernia. The patient was a 62-year-old white female
      with a reducible left lower quadrant anterior abdominal wall bulge consistent
      with a Spigelian hernia. At the time of surgery, we exposed the posterior rectus
      fascia and modified our extraperitoneal inguinal hernia technique by passing the
      balloon dissector in a more lateral orientation. This created a unilateral
      preperitoneal space with adequate room for dissection and mesh fixation. The
      Spigelian defect was easily identified. Its preperitoneal fat contents were
      reduced, and a 5-mm laparoscopic tacking device was used to secure a piece of
      prolene mesh. The patient was discharged home with no complications. Placement of
      the mesh in the preperitoneal space avoids direct interaction of the mesh
      prosthesis and the intraperitoneal viscera. In conclusion, we find that a
      laparoscopic totally extraperitoneal approach is technically feasible and
      advantageous when a Spigelian hernia is diagnosed preoperatively.

PMID- 11967700
TI  - Primary malignant melanoma of the esophagus: a case report.
AB  - Primary malignant melanoma of the esophagus is an uncommon tumor associated with
      a poor survival (5% at 5 years), even when resected at an early stage. Because
      its symptoms are no different from those of other malignant tumors of the
      esophagus, histopathologic examination is usually needed to reach a definitive
      diagnosis. A 57-year-old white nonsmoking nonalcoholic woman was referred to our
      department after 2 months of increasing dysphagia, odynophagia, and weight loss
      (5 kg in 2 months). Esophagogastroscopy revealed a dark blue, pediculated,
      polypoid lesion. Biopsies were taken. Endoscopic ultrasound showed a hyperechoic
      heterogeneous tumor. Barium esophagogram showed a filling defect of ~ 6 cm in the
      middle-low esophagus, and thoracic and abdominal computed tomography (CT) scan
      showed a well-delimited esophageal tumor with no clear lymph node enlargement.
      The pathology report described a proliferation of small spindle-shaped or
      stellate cells arranged in a spiral or fascicular structure. All tumor cells were
      intensively positive for immunoreaction, using HMB45 antimelanoma antibodies. To
      remove the tumor, distal esophagectomy through a double abdominal and thoracic
      approach was performed. No postoperative complications were reported and no chemo
      or radiotherapy was given. The patients is still alive with no evidence of
      recurrence at 9 months after the operation.

PMID- 11967701
TI  - Right hepatic duct emptying into the cystic duct: report of a case.
AB  - BACKGROUND: Anomalous insertion of the right hepatic duct into the cystic duct is
      a rare anatomic variation. At this writing, only nine cases have been reported in
      the literature. In the patients presenting with this anomaly, the surgeon may
      accidentally transect the right hepatic duct during cholecystectomy. METHODS: We
      encountered a case of anomalous insertion of the right hepatic duct into the
      cystic duct, which was clearly demonstrated in the intraoperative cholangiography
      during laparoscopic cholecystectomy. RESULTS: As the half-cut point of the cystic
      duct happened to be on the gallbladder side of the cystic duct, cholecystectomy
      was accomplished laparoscopically. CONCLUSIONS: In anomalous insertion of the
      right hepatic duct into the cystic duct, hepatic duct transection could happen.
      Preoperative precise evaluation of the biliary duct, awareness of potential
      biliary variations, and identification of all anatomic structures before ligation
      and division were essential to prevent bile duct injury.

PMID- 11967702
TI  - Previous appendicitis may affect peritoneal overlap of the mesh in laparoscopic
      inguinal hernia repair.
AB  - Laparoscopic inguinal hernia repair is now increasingly performed in bilateral
      and recurrent groin hernias. The avoidance of direct exposure of the commonly
      used meshes to the abdominal viscera is considered essential to reduce the risk
      of bowel adhesions. We report a case of bilateral inguinal hernia repair in a
      patients who had had an appendectomy performed 8 years earlier for a perforated
      appendicitis. Probably as a result of previous inflammation, any attempt to
      dissect the preperitoneal layer in the right side resulted in peritoneal
      lacerations. Since the peritoneum could not be used to cover the mesh, we decided
      to position an expanded polytetrafluoroethylene (e-PTFE) mesh to avoid
      postoperative adhesions. The mesh was fixed with tacks to the symphysis pubis,
      Cooper's ligament, the ilio-pubic tract, and the transversalis fascia 2 cm above
      the hernia defect. This case suggests that in patient with previous appendicitis,
      a difficult preperitoneal dissection can be expected. In such cases, especially
      in young patients for whom future surgical operations cannot be excluded, any
      attempt to reduce adhesions is justified. At the present time, the use of e-PTFE
      meshes, which induce no tissue reaction, is a good option in this situation.

PMID- 11967703
TI  - Anxiety disorder after laparoscopic refundoplication as a cause of dysphagia.
AB  - Side effects of laparoscopic antireflux surgery doubtless have a negative effect
      on patients' satisfaction with surgical outcome and quality of life. Until now,
      side effects of laparoscopic antireflux surgery such as dysphagia have not been
      reported as associated with the origin of psychiatric disorders. We report the
      case of a 71-year-old man who underwent laparoscopic refundoplication because of
      a "slipping" Nissen 2 years after primary intervention. After operation, the
      patient suffered from severe dysphagia and required pneumatic dilation. In this
      patient, severe dysphagia has caused panic disorder. Complete relief of dysphagia
      was achieved by single dilation. In contrast, panic symptoms in relation to daily
      ingestion continued for at least 6 weeks after surgery. A mild level of anxiety
      without panic symptoms existed for the first 3 months after reoperation.

PMID- 11967704
TI  - Abdominal wall sinus due to impacting gallstone during laparoscopic
      cholecystectomy: an unusual complication.
AB  - During laparoscopic cholecystectomy, perforation of the gallbladder can occurs in
      < or = 20% of cases, while gallstone spillage occurs in < or = 6% of cases. In
      most cases, there are no consequences. Gallstones can be lost in the abdominal
      wall as well as the abdomen during extraction of the gallbladder. The fate of
      such lost gallstones, which can lead to the formation of an abscess, an abdominal
      wall mass, or a persistent sinus, has not been studied adequately. Herein we
      report the case of a persistent sinus of the abdominal wall after an emergent
      laparoscopic cholecystectomy in an 82-year-old woman with gangrenous
      cholecystitis and perforation of the friable wall in association with an empyema
      of the gallbladder. The culture of the obtained pus was positive for Escherichia
      coli. After a small leak of dirty fluid from the wound of the epigastric port
      site of 4 months' duration, surgical exploration under local anesthesia revealed
      that the sinus was caused by spilled gallstones impacting into the abdominal wall
      between the posterior sheath and left rectus abdominalis muscle. The removal of
      the stones resulted in complete healing. Long-term complications after
      laparoscopic cholecystectomy involving the abdominal wall are rare but important
      possible consequences that could be avoided.

PMID- 11967705
TI  - Gallstone ileus as a complication of cholecystolithiasis.
AB  - Biliary fistula and gallston ileus are rarely found. The diagnosis is difficult.
      Gallstone ileus requires urgent and appropriate surgical therapy. Enterolitotomy
      remains the gold standard of operative treatment for gallstone ileus, but
      additional procedures of one-stage cholecystectomy and repair of fistula are
      necessary. Some researchers advise first to resolve the gallstone ileus and then
      to perform the elective operation for gallstone disease in more ideal
      circumstances. Our case had clinical evidence of ileus, which was confirmed by
      radiological exam. Ultrasonographic examination performed before operation did
      not confirm the presence of gallbladder; it did not detect a large stone located
      in the intestine. The patient, a 75-year-old woman, was operated on. During the
      procedure it was shown that the second part of the duodenum was involved in a
      scar and displaced to the hepatic hilus. There was no gallbladder; it was
      probably destroyed by a long-lasting vesicoduodenal fistula. Cholangiography also
      did not detect the gallbladder. Biliary passage through the common bile duct was
      sufficient. The hole in the duodenum wall was sutured, and Kehr drain was
      inserted into the common bile duct. The gallstone was removed by incision of the
      intestine down to the obstruction. The postoperative period was complicated by a
      small suppuration of the laparotomy wound. Vesicoduodenal fistula present for a
      long time can lead to atrophy of the gallbladder. The one-stage procedure seems
      to be appropriate if biliary fistula and gallstone ileus are found.

PMID- 11967706
TI  - Laparoscopic extraction of a swallowed fork in a patient first diagnosed with
      bulimia nervosa.
AB  - Swallowed foreign bodies are relatively common problem. The first reports date
      back about 3000 years. The first medical report was done by Mestivier in 1759.
      Several studies show that up to 90% of the foreign bodies (FBs) pass
      spontaneously and 10% to 20% require an endoscopic removal. Surgical intervention
      is only indicated in approximately 1% of the cases. Surgical intervention is only
      necessary, for example, when large or sharp FBs are involved because of the
      potential risk of perforation and obstruction. The surgical therapy can be
      carried out by means of laparotomy or laparoscopy; laparoscopy has to be given
      the first priority whenever possible. The advantages of a laparoscopic procedure
      are well-known: reduced postoperative pain, better lung function, less
      postoperative bowel obstruction, shorter hospital stay, and faster
      reconvalescence. We report an unusual case of an unintentional ingested fork,
      which required a laparoscopic extraction using three trocars. The 20-year-old
      female patient was then subsequently diagnosed with bulimia nervosa for the first
      time during her hospital stay. The patient was discharged home on the fourth
      postoperative day after an unremarkable course.

PMID- 11967707
TI  - Laparoscopic extirpation of a giant ovarian cyst.
AB  - BACKGROUND: The differential diagnosis of unilocular intraabdominal cysts
      includes ovarian, gastrointestinal, urological, and lymphatic processes. They
      occur at all ages and can be benign or malignant. METHODS: We present a case of a
      17-year-old female with asymptomatic abdominal distension. Ultrasonography (US)
      revealed a 20 x 21-cm unilocular cystic mass with smooth surface lining.
      Paracentesis was performed during diagnostic laparoscopy, recovering more than 7
      L of clear fluid. The cyst and left adnex were completely removed
      laparoscopically and diagnosis of ovarian cystadenoma was made. The patient made
      a quick and uneventful recovery. CONCLUSIONS: In all cases of abdominal
      distension, US must be performed and a tumor marker profile consisting of AFP,
      LDH, testosterone, estradiol, and CA-125 must be established in order to
      differentiate between benign and malignant processes. When the latter is
      suspected, additional computerized tomographic scanning must be performed. In
      this case, a normal tumor marker profile and benign ultrasonographic appearance
      excluded the possibility of malignancy. Conventional treatment in these large
      cysts is laparotomy. We propose that complete laparoscopic drainage and
      extirpation should be the treatment of choice, regardless of cystic size.

PMID- 11967708
TI  - Yttrium-aluminum-garnet laser therapy of esophageal granular cell tumor.
AB  - BACKGROUND: Granular cell tumor (GCT) is a rare lesion. Approximately 4% to 6% of
      these tumors occur in the gastrointestinal tract, one-third of them affecting the
      esophagus. Almost all GCTs are benign lesions. Approximately 1% to 3% are
      malignant. Endoscopic ultrasonography (EUS) is a diagnostic support. The best
      treatment for esophageal GCT is not yet clear, whether surgical excision,
      periodic observation, endoscopic excision, or yttrium-aluminum-garnet (YAG) laser
      therapy. METHODS: From November 1992 to December 2000, four patients with GCTs of
      the esophagus were observed. All the patients underwent EUS evaluation and
      endoscopic YAG laser therapy of the esophageal neoplasm. At each session, a
      biopsy at the tumor site was obtained. The treatment was continued until
      endoscopic and histologic evidence of the tumor disappeared. RESULTS: After the
      YAG laser therapy, no evidence of the tumor was found in any of the four patients
      with esophageal GCT. At this writing, the patients remain disease free after a
      mean follow-up period of 66 months. No complication has been observed. Only four
      sessions for each patient were necessary to eliminate the tumor. CONCLUSIONS:
      Therapy with YAG laser was effective in all four patients with esophageal GCT,
      and complete necrosis of the submucosal neoplastic cells was achieved. Endoscopic
      YAG laser therapy appears to be a good compromise between esophageal dissection
      and long-term observation without tumor excision. Esophageal laser therapy is
      safe if correctly used, and previous EUS evaluation increases treatment safety.

PMID- 11967709
TI  - Ventricular fibrillation caused by electrocoagulation during laparoscopic
      surgery.
AB  - A 35-year-old man with morbid obesity was admitted to our hospital to undergo
      gastric banding gastroplasty by the laparoscopic approach. Aside from his morbid
      adiposity, with a body mass index (BMI) of 49.9 kg/m2, the patient was healthy.
      During the procedure, he developed ventricular fibrillation (VF) while a
      diathermic knife was being used. After defibrillation, his heart rate returned to
      normal. The postoperative clinical course was uneventful, and there was no
      evidence of permanent heart failure. Although the VF could have been caused by
      patient- or material-related variables, it was most likely the result of unwanted
      electrical effects. Specifically, the occurrence of an arc between the patient's
      tissue and the tip of the electrode during cutting in the coagulation mode can
      lead to low-frequency current. The modified low-frequency current may produce
      arrhythmias. Thus, the use of the coagulation mode to cut tissue in the cardiac
      region during laparoscopic procedures could increase the risk for arrhythmias. An
      understanding of the physical principles of electrosurgery, as well as
      familiarity with the equipment and its various functions, is essential for the
      patient's safety. In addition, cardioversion equipment should be readily
      available on every surgical unit.

PMID- 11967710
TI  - Laparoscopic resection of a large periadrenal nonmalignant pheochromocytoma.
AB  - This is, to our knowledge, the first case description of an extraadrenal
      pheochromocytoma located in the periadrenal fat. Pheochromocytoma is a tumor that
      originates in the chromaffin tissue. Extraadrenal pheochromocytomas have been
      described commonly in locations such as the organ of Zuckerkandle (29%); the
      bladder (12%); the sacrum, testis, rectum, and pelvic floor (2%); the upper
      abdomen in association with celiac, superior mesenteric, and inferior mesenteric
      ganglia (43%); the thorax (12%); and the neck (2%), most commonly in association
      with the ninth or tenth cranial nerve ganglion. Our patient was a 40-year-old
      woman known to have had an adrenal mass for the last 4 years. She was referred
      for surgery because of an increase in the size of the mass to 11 cm. Laparoscopic
      adrenalectomy was performed via a posterior flank approach. The pathology report
      was of periadrenal fat pheochromocytoma, with positive staining for
      synaptophysin, chromogranin, and vimentin. The patient was discharged on
      postoperative day 3. The unique feature in this case was the uncommon location of
      the extraadrenal tumor: the supraadrenal fat. The other unique finding in this
      case was that the pheochromocytoma was neither symptomatic nor malignant, common
      features of extraadrenal masses.

PMID- 11967711
TI  - Aortic injury during laparoscopic fundoplication: an underreported complication.
AB  - BACKGROUND: Advances in video equipment, instrumentation, and laparoscopic skills
      have enabled the performance of an increasing variety of procedures using
      minimally invasive techniques. Additionally, the public is more aware of the
      benefits of laparoscopic surgery, including decreased postoperative pain and
      shortened recovery period. Surgical treatment of gastroesophageal reflux disease
      (GERD) is blossoming as a result. As with all surgical procedures, complications
      can occur. This case report describes a complication of laparoscopic
      fundoplication not previously reported. Also summarized is a review of all
      complications associated with minimal access fundoplication reported in the
      literature. METHODS: After appropriate evaluation for surgical treatment of GERD
      that revealed a nonspecific esophageal motility disorder, a 52-year-old female
      underwent laparoscopic Toupet fundoplication. During the procedure, a needle
      injury occurred to the aorta at the level of the hiatus. Despite exploration
      during the original procedure, which had been converted to laparotomy, and at two
      subsequent operations, the intermittent bleeding source was not found. The
      patient eventually died secondary to blood loss. The aortic injury was discovered
      postmortem. CONCLUSION: A variety of intraoperative complications associated with
      laparoscopic fundoplication have been reported, including gastric, esophageal,
      and bowel perforations, cardiac tamponade, pneumothorax, celiac artery
      thrombosis, bleeding, and death. Although this is the first reported aortic
      injury during minimally invasive fundoplication not related to trocar placement,
      discussion with other surgeons indicates that this is not the only occurrence of
      this complication.

PMID- 11967712
TI  - Bilateral anterior minithoracotomy with video assistance for lung volume
      reduction surgery and pulmonary metastasectomy.
AB  - Incisional access to pulmonary pathology involving both lungs has often involved
      bilateral standard thoracotomies, median sternotomy, and, recently, sequential
      lateral video-assisted thoracic surgical approaches. Significant problems are
      inherent to each of these approaches. We introduce a hybrid technique of
      bilateral simultaneous minithoracotomy with video assistance as an alternative to
      these other surgical approaches.

PMID- 11967713
TI  - Principles of privileging and credentialing for endoscopy and colonoscopy.

PMID- 11967715
TI  - Potential causes, mechanisms, and implications of post exercise hypotension.
AB  - Post exercise hypotension (PEH) is a phenomenon of a prolonged decrease in
      resting blood pressure in the minutes and hours following acute exercise.
      Knowledge of PEH is potentially useful in designing first line strategies against
      hypertension as well as allowing a further understanding of blood pressure
      regulation in both health and disease. Following a brief review of blood pressure
      responses to exercise, this paper will provide a current and comprehensive
      summary of PEH and integrate the current state of knowledge surrounding it.

PMID- 11967714
TI  - Harmful effects of dietary salt in addition to hypertension.
AB  - In addition to raising the blood pressure dietary salt is responsible for several
      other harmful effects. The most important are a number which, though independent
      of the arterial pressure, also harm the cardiovascular system. A high salt intake
      increases the mass of the left ventricle, thickens and stiffens conduit arteries
      and thickens and narrows resistance arteries, including the coronary and renal
      arteries. It also increases the number of strokes, the severity of cardiac
      failure and the tendency for platelets to aggregate. In renal disease, a high
      salt intake accelerates the rate of renal functional deterioration. Apart from
      its effect on the cardiovascular system dietary salt has an effect on calcium and
      bone metabolism, which underlies the finding that in post-menopausal women salt
      intake controls bone density of the upper femur and pelvis. Dietary salt controls
      the incidence of carcinoma of the stomach and there is some evidence which
      suggests that salt is associated with the severity of asthma in male asthmatic
      subjects.

PMID- 11967716
TI  - Sleep actigraphy in hypertensive patients with the 'non-dipper' blood pressure
      profile.
AB  - Several prospective studies have demonstrated a higher cardiovascular
      complication rate in patients with a non-dipping compared with a dipping blood
      pressure profile. However, the extent of blood pressure reduction during sleep
      can be highly variable in an individual patient, and a repeat ambulatory blood
      pressure study commonly shows a change in category. The reasons for this
      variability are not clear. In general, hypertensive patients with a non-dipper
      blood pressure profile have higher actigraphy-measured activity during time in
      bed than dipper hypertensive patients but no analysis of actigraphy-determined
      sleep parameters has been published. We therefore prospectively studied 52
      hypertensive patients who were off antihypertensive drugs for at least 3 weeks
      and who underwent simultaneous ambulatory and wrist actigraphy monitoring. All
      patients were clinically free of any sleep-related disorder. The blood pressure
      profile was labelled dipper when the change in mean awake blood pressure to sleep
      blood pressure was 10% or higher and non-dipper if less than 10%. Overall
      activity levels were higher during the time in bed in the non-dipper group
      compared with the dipper group. An inverse relationship of daytime activity with
      age was seen in men (r = -0.54, P = 0.001) but not in women (r = -0.06, P =
      0.79). Both groups of hypertensive patients had a similar total time in bed (458
      +/- 92 min, in dippers and 433 +/- 106 min in non-dippers, P = 0.39). Sleep
      latency (time to onset of sleep after getting into bed) was a median of 7 min in
      dippers and 15 min in non-dippers (P = 0.10). In addition, dipper hypertensives
      spent more of the time in bed asleep than non-dippers (87% vs 76%, P = 0.004).
      Logistic regression analysis revealed that body mass index, kg/m(2) (OR, 1.3),
      and night-time activity (units/min) (OR, 1.1) were predictive of a non-dipping
      blood pressure profile. These data show a possible disturbance of sleep in non
      dipper hypertensive patients.

PMID- 11967717
TI  - Ascending fractional pulse pressure closely relating to large artery function.
AB  - It is not known whether ascending fractional pulse pressure (PPf) is related to
      large artery function. This study was to evaluate whether PPf is associated with
      large artery function by augmentation index. A total of 190 subjects were
      enrolled (age range: 50 to 78 years) who had normal contractions, no local
      asynergy, and no history of myocardial infarction. The ascending aortic pressure
      was measured using a fluid-filled system. To quantify the relative magnitude of
      the pulsatile to mean artery pressure, we normalised the pulse pressure to the
      mean pressure and referred to this value as PPf and the association between the
      PPf and the augmentation index was investigated. Augmentation index showed
      significant associations with PPf by univariate analysis (R = 0.690, P < 0.001).
      The associations between PPf and the factors influencing large artery function
      were examined by multivariate analysis, and PPf revealed significant associations
      with age, mean aortic pressure, heart rate and type 2 diabetes (R(2) = 0.477, P <
      0.001). The results were that ascending aortic PPf is closely associated with
      large artery function detected by augmentation index.

PMID- 11967718
TI  - Microalbuminuria is associated with unfavourable cardiac geometric adaptations in
      essential hypertensive subjects.
AB  - We sought in this study to examine the relationship between microalbuminuria and
      cardiac geometry since a slight increased urinary albumin excretion (UAE) and
      increased left ventricular (LV) mass have both been identified as predictors of
      cardiovascular events in hypertensive subjects. For this purpose,
      microalbuminuria was determined in three non-consecutive 24-h urine samples as
      UAE of 20-200 mg/24 h in a group of 249 untreated hypertensive subjects.
      Echocardiographic classification of patients into LV geometric patterns was based
      on relative wall thickness values and on gender-specific values for LV mass index
      (LVMI). The group of patients with microalbuminuria (n = 119) was matched for
      age, sex, body mass index, smoking status and plasma cholesterol level with the
      group of patients without microalbuminuria (n = 130). Subjects with
      microalbuminuria had significantly increased LVMI (111 vs 90 g/m(2), P < 0.0001),
      relative wall thickness (0.46 vs 0.41, P < 0.001) and office systolic and
      diastolic blood pressure (161 vs 148 and 101 vs 97 mmHg, respectively, P <
      0.005). For the pooled population, UAE was positively correlated to LVMI (r =
      0.46, P < 0.001) and relative wall thickness (r = 0.47, P < 0.001). In the entire
      population, normal LV geometry, concentric LV remodelling, eccentric and
      concentric LV hypertrophy was found in 34%, 33%, 12% and 21%, respectively. The
      prevalence of normal LV geometry was significantly higher in normoalbuminuric
      compared with microalbumnuric subjects (55 vs 14%, P < 0.001) while the
      prevalence of concentric LV hypertrophy was significantly higher in
      microalbuminuric compared with normoalbuminuric subjects (32 vs 5%, P < 0.0001).
      Multiple regression analysis revealed that concentric LV hypertrophy was
      significantly associated with increased values of UAE and mean arterial pressure.
      In conclusion, the higher prevalence of unfavourable LV geometric patterns in
      hypertensive subjects with microalbuminuria compared with those without
      microalbuminura, may account for the worse cardiovascular outcomes associated
      with the presence of an increased UAE in hypertensive subjects.

PMID- 11967719
TI  - Lack of correlation between two methods for the assessment of salt sensitivity in
      essential hypertension.
AB  - The existence of a heterogeneous blood pressure (BP) response to salt intake, a
      phenomenon known as salt sensitivity, has increasingly become a subject of
      clinical hypertension research, and has important clinical and prognostic
      implications. However, two different methodologies are currently used to diagnose
      salt sensitivity. The aim of the present study was to compare the BP response to
      intravenous sodium load and depletion on the one hand, and to changes in dietary
      salt intake on the other, in order to assess salt sensitivity in a group of
      essential hypertensive patients. Twenty-nine essential hypertensives underwent
      two different procedures separated by 1 month: a dietary test consisting of a 2
      week period of low (20 mmol/day) and high (260 mmol/day) salt intakes, and an
      intravenous test consisting of a 2 litre saline load over a 4-h period, followed
      by 1 day of low (20 mmol) salt intake and furosemide (40 mg/8 h orally)
      administration. BP was registered at the end of every period using 24-h
      ambulatory BP monitoring. In the whole group of hypertensive patients studied,
      both low salt intake and furosemide administration significantly (P < 0.01)
      decreased mean BP. Correlation coefficients of BP changes obtained using the two
      methodologies were between 0.3 and 0.4. Moreover, coefficients of agreement
      between the oral and the intravenous tests, using several cut points for BP
      changes, were systematically below 0.5, thus indicating a misclassification of
      salt sensitivity greater than 50%, depending on the method used. None of the cut
      points for BP changes during furosemide administration showed a good combination
      of sensitivity and specificity compared with changes in response to low dietary
      salt. The present results indicate that the diagnosis of salt-sensitive
      hypertension should be based on the BP response to changes in dietary salt
      intake, while BP response to saline and furosemide administration leads to a
      systematic misclassification of more than 50% of patients, even using different
      cutpoints for changes in BP.

PMID- 11967720
TI  - Effect of angiotensin II on pulse wave velocity in humans is mediated through
      angiotensin II type 1 (AT(1)) receptors.
AB  - The objective of this study was to examine the effect of angiotensin II (Ang II)
      and angiotensin II type 1 (AT(1)) receptor blockade on pulse wave velocity (PWV)
      in healthy humans. We studied nine young male volunteers in a double-blind
      randomised crossover design. Carotid-femoral PWV (an index of arterial stiffness)
      was measured by using a Complior machine. Subjects were previously treated for 3
      days with once-daily dose of either a placebo or valsartan 80 mg. On the third
      day, they were infused with either placebo or 5 ng/kg/min of Ang II over 30 min.
      Subjects thus received placebo capsule + placebo infusion (P), valsartan +
      placebo infusion (V), placebo + Ang II infusion (A), and valsartan + Ang II
      infusion (VA) combinations. Heart rate (HR), blood pressure and PWV were recorded
      at baseline and then every 10 min during infusion and once after the end of
      infusion. There were significant increases in systolic blood pressure (SBP),
      diastolic blood pressure (DBP) and mean arterial pressure (MAP) with A compared
      with P (P = 0.002, P = 0.002, P = 0.001 respectively). These rises in blood
      pressure were completely blocked by valsartan. A significant rise in PWV by A was
      seen compared with P (8.38 +/- 0.24 vs 7.48 +/- 0.24 m/sec, P = 0.013) and was
      completely blocked by valsartan; VA compared with P (7.27 +/- 0.24 vs 7.48 +/-
      0.24 m/sec, P = NS). Multiple linear regression analysis showed that blockade of
      Ang II induced increase in blood pressure by valsartan contributed to only 30% of
      the total reduction in Ang II induced rise in PWV (R(2) = 0.306). The conclusions
      were that valsartan completely blocks the effect of Ang II on PWV. The effect of
      Ang II on PWV is mediated through AT(1)receptors. Reduction in PWV by Ang II
      antagonist is not fully explained by its pressure lowering effect of Ang II and
      may be partially independent of its effect on blood pressure.

PMID- 11967721
TI  - Ethnic differences in blood pressure and the prevalence of hypertension in
      England.
AB  - The objective of this study was to examine the prevalence of hypertension and
      mean blood pressures among Afro-Caribbeans and South-Asians in England compared
      with Caucasians. Data from the Birmingham Factory Screen, Birmingham INTERSALT
      volunteers, and four West Midlands churches were combined into a single database
      (n = 2853), since all three studies employed identical methods. The cohort
      comprised 2169 (76%) Caucasians (71% men); 453 (16%) Afro-Caribbean (60% men);
      and 231 (8%) South-Asian men. The results were that overall prevalence of
      hypertension (> or =160/95 mm Hg or taking antihypertensives) was greater in both
      Afro-Caribbean men (31%) and women (34%) (both P < 0.001), compared with
      Caucasians (19% and 13% respectively), while South-Asian men had a similar
      overall prevalence to Caucasians (16%). Compared with Caucasians, Afro-Caribbeans
      had significantly higher mean systolic blood pressure, with higher mean diastolic
      blood pressures evident among Afro-Caribbean women. After adjustment for age,
      body mass index, smoking, and weekly alcohol intake, the odds ratios (95% CI) for
      being hypertensive were 1.56 (1.14 to 2.13; P = 0.005) and 2.40 (1.51 to 3.81; P
      = 0.0002) for Afro-Caribbean men and women, respectively and 1.31 (0.88 to 1.97;
      P = 0.19) for South-Asian men, compared with Caucasians. In conclusion the
      prevalence of hypertension and mean blood pressures are higher among Afro
      Caribbeans compared with Caucasians. South-Asian men had similar rates of
      hypertension and mean blood pressures to Caucasians.

PMID- 11967722
TI  - Hypertension and renovascular disease: follow-up on 100 renal vein renin
      samplings.
AB  - The clinical value of renal vein renin sampling (RVRS) as a prognostic tool in
      the treatment of renovascular hypertension was evaluated. One hundred consecutive
      patients were included over a 4-year period of time. About half of the patients
      (49%) were treated interventionally by PTRA (21%), nephrectomy (20%), or vascular
      surgery (8%). Seven patients (15%) were cured and 15 (32%) had improved
      (reduction in antihypertensive medicine) after 6 months follow-up, whereas three
      patients (6%) were cured and 12 (26%) improved after 3-4 years follow-up. Thus,
      the number of patients cured or improved is comparable with the results from our
      department reported 20 years ago. However, in the present report, more than twice
      as many patients were enrolled, leading to double costs. Different indices of
      lateralisation of the renin generation were calculated for the use in cases of a
      shrunken kidney (functional share < or =15%). None of the indices clearly
      discriminated between the patients who did benefit from intervention, and those
      who did not. The only positive finding was that a peripheral renin concentration
      lower than 8 mlU/l predicted no effect of intervention, which might lead to the
      exclusion of 11% of the patients before entering the diagnostic programme. We
      conclude that the RVRS demands a very restrictive referral pattern if it should
      be of prognostic value for the blood pressure outcome after intervention. No
      indices of lateralised renin concentrations proved high predictive value.
      However, a peripheral renin concentration low in the normal range seems useful as
      an indicator of no benefit from intervention.

PMID- 11967723
TI  - Successful laparoscopic operation of bilateral pheochromocytoma in a patient with
      Beckwith-Wiedemann syndrome.
AB  - We report the case of a 20-year-old female patient with Beckwith-Wiedemann
      syndrome presenting with high blood pressure and bilateral adrenal
      pheochromocytoma successfully removed with laparoscopy in the same time. To our
      knowledge, the present case is the first observation of a bilateral
      pheochromocytoma occurring in the Beckwith-Wiedemann syndrome. It provides
      further support for a genetic anomaly in this condition. Our case also indicates
      the interest of laparoscopy for the surgical treatment of adrenal
      pheochromocytoma, even in bilateral tumors.

PMID- 11967724
TI  - A high level of awareness but a poor control of hypertension among elderly
      Greeks. The Nemea primary care study.

PMID- 11967726
TI  - Angiotensin II as a cardiovascular risk factor.
AB  - A renin-angiotensin level that is inappropriately high for the systemic blood
      pressure and the state of sodium balance is now recognized to be one of the
      modifiable cardiovascular risk factors. Angiotensin acts both as a circulating
      hormone and as a locally acting paracrine/autocrine/intracrine factor. The
      adverse effects of angiotensin on the heart include the mechanical results of
      elevated resistance to the pumping function of the myocardium, as well as the
      effects of neurohumoral abnormalities on various cardiac structures. In addition,
      cardiac damage follows acute ischaemic injury or chronic energy starvation due to
      coronary artery disease, attributable to either mechanical obstruction
      (atherosclerotic and/or thrombotic) or functional stenosis (vasospasm).
      Activation of the renin-angiotensin system has several haemodynamic and humoral
      consequences, all of which may damage the myocardium. These include acute
      myocardial ischaemia, left-ventricular hypertrophy, arrhythmias, alterations in
      the coagulation-fibrinolysis equilibrium, increased oxidative stress, and pro
      inflammatory activity. A brief review of some of the mechanisms by which
      activation of the renin-angiotensin system can inflict damage on the heart is
      presented.

PMID- 11967728
TI  - The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview.
AB  - The new orally active angiotensin II (A II) type-1 receptor antagonist olmesartan
      medoxomil is a prodrug, which is rapidly converted in vivo to the active
      metabolite, olmesartan. The pharmacology, antihypertensive efficacy and safety of
      olmesartan medoxomil and/or the pharmacologically active metabolite, olmesartan,
      have been evaluated in both non-clinical and clinical models. Orally administered
      olmesartan medoxomil is rapidly absorbed from the gastrointestinal tract and
      converted during absorption to olmesartan, which is subsequently excreted without
      further metabolism. Peak plasma concentrations of olmesartan occur 1-3 h after
      administration, after which concentrations decrease with an elimination half-life
      of 10-15 h. The absolute bioavailability of olmesartan from olmesartan medoxomil
      tablets is 28.6%. In a single-dose crossover study in 16 patients with mild-to
      moderate hypertension receiving a sodium-restricted diet, statistically
      significant lowering of mean 24-h blood pressure was seen at doses of 10-80 mg.
      Evaluation of 14 phase II/III studies has confirmed the antihypertensive efficacy
      of olmesartan medoxomil in over 3500 patients who received the drug for up to 2
      years. Frequencies of adverse events during treatment with olmesartan medoxomil
      and placebo are similar, with no evidence of a dose response. There are no
      clinically significant effects on laboratory parameters, and the drug-interaction
      potential of olmesartan medoxomil is low. Current indications are that olmesartan
      medoxomil is a true once-daily, orally active A II antagonist with good
      antihypertensive efficacy and a favourable adverse-event profile. Clinical
      pharmaco- dynamic and efficacy studies support a usual dose of 20 mg once daily,
      increasing to 40 mg if needed.

PMID- 11967727
TI  - Anti-atherosclerotic efficacy of olmesartan.
AB  - The possible inhibition of lipid deposition into vascular tissues by a novel
      angiotensin II type 1 receptor antagonist, olmesartan, was investigated in a
      primate high-cholesterol model. Twelve monkeys that were fed a high-cholesterol
      (4% cholesterol and 6% corn oil) diet for 6 months were divided into two groups:
      one group was given olmesartan medoxomil (10 mg/kg per day), and the other group
      was given no medication. A further control group of six monkeys was fed a normal
      diet throughout the study. The level of low-density lipoprotein (LDL) cholesterol
      was increased by the high-cholesterol diet, whereas that of high-density
      lipoprotein (HDL) cholesterol was decreased. Olmesartan decreased the areas of
      lipid deposition on the aortic surface and intimal cross-section area, but not
      the mean blood pressure and the levels of LDL and HDL cholesterol. The relaxation
      response of isolated carotid arteries to acetylcholine was suppressed in the high
      cholesterol group, but this was improved by olmesartan. Olmesartan inhibited the
      accumulation of macrophages in the intimal layer. Serum levels of transforming
      growth factor (TGF)-beta1, macrophage colony-stimulating factor (M-CSF) and
      intracellular adhesion molecule (ICAM)-1 were increased in monkeys fed the high
      cholesterol diet, but they were suppressed by olmesartan, although the decrease
      was not significant. Olmesartan reduced lipid deposition, accompanied by the
      improvement of vascular functions and the inhibition of macrophage accumulation
      in the intimal layer and showed a trend towards the suppression of serum TGF
      beta1, M-CSF and ICAM-1.

PMID- 11967729
TI  - Antihypertensive efficacy of olmesartan compared with other antihypertensive
      drugs.
AB  - The therapeutic profile of olmesartan medoxomil, which is a recently developed
      angiotensin II (A II) receptor blocker, has been compared with four commonly used
      antihypertensive therapeutic drugs (atenolol, captopril, felodipine and losartan)
      in five separate multicentre, randomised, double-blind, parallel-group, phase III
      trials. The trials were designed to compare the efficacy of individually
      optimised dosages of olmesartan medoxomil and the comparator agent. The primary
      efficacy variable in all trials was the mean change from baseline to week 12 in
      trough mean sitting diastolic blood pressure (DBP). Olmesartan medoxomil (10-20
      mg once daily (o.d.)) showed similar efficacy to atenolol (50-100 mg o.d.), both
      in patients with mild-to-moderate hypertension and, when given together with
      hydrochlorothiazide (HCTZ) 25 mg o.d., in patients with moderate-to-severe
      hypertension. Olmesartan medoxomil (20-40 mg o.d.) was also similar in efficacy
      to felodipine (5-10 mg o.d.) in reducing BP in patients with mild-to-moderate
      hypertension. Compared with captopril (12.5-50 mg twice daily (b.i.d.)) and
      losartan (50-100 mg o.d.), in patients with mild-to-moderate hypertension,
      olmesartan medoxomil (5-20 mg o.d. and 10-20 mg o.d., respectively) was
      significantly superior in terms of lowering DBP from baseline to week 12. In
      terms of the secondary efficacy variable, which was mean change from baseline to
      week 12 in trough mean sitting systolic BP, olmesartan showed significant
      superiority to atenolol, captopril and losartan in patients with mild-to-moderate
      hypertension. In the longer term, compared with losartan, a lower percentage of
      olmesartan-treated patients required concomitant HCTZ after 12 weeks of therapy.
      Olmesartan was well tolerated in all studies.

PMID- 11967730
TI  - [Immunomodulation in ophthalmology].

PMID- 11967731
TI  - [Dry eye syndrome: is there any hope for a curative therapy?].

PMID- 11967732
TI  - [Drug therapy combinations].

PMID- 11967733
TI  - [Prevalence of drusen in homes for the elderly].
AB  - PURPOSE: To establish the prevalence of drusen in a population of over-65 year
      subjects residing in institutions. MATERIAL AND METHOD: A medical interview,
      ophthalmological examinations and midriatic retinography were performed in 392
      older-than-65 year subjects living in homes for the elder (784 eyes). Each eye
      was reviewed by means of the Wissconsin Age-Related Maculopathy Grading System,
      in order to determine drusen frequency. RESULTS: Druses frequency totalled 33.3%.
      A great trend to symmetry was observed; bilateral in 23% of patients. The most
      frequent finding was multiple units (40 to 59 per eye), well defined soft drusen
      of 125 micrometer in size, which showed very little tendency to confluence.
      Twelve to 24% of macular area was affected by drusen. Subjects between ages of 65
      to 74, presented the highest frequence. Drusen decreased with age from 75 years
      upwards. CONCLUSION: The observed drusen frequency found appear lower than those
      described in other studies outside our country, perhaps due to higher prevalence
      of media opacities. Midriatic retinography can be a good screening method for the
      detection of drusen.

PMID- 11967734
TI  - [Glutathione-related enzymes activity during vitrectomy. Effect of BSS Plus(R) in
      retinal tissue].
AB  - PURPOSE: To determine changes in the retinal activity of two enzymes related to
      the glutathione metabolism (Glutathione synthetase -GSHS- and glutathione
      reductase -GSSGR-) after vitrectomy using BSS Plus(R). MATERIAL AND METHODS:
      Forty-five pigmented rabbits were distributed in 6 groups: group I (GSHS control
      in retinal tissue); Group II (analysis of GSHS at 3 hours post-vitrectomy); Group
      III (determination of GSHS at 48 hours after vitrectomy); Group IV (GSSGR control
      in retinal tissue); Group V (measurement of GSSGR at 3 hours post-surgery) and
      Group VI (study of GSSGR at 48 hours post-vitrectomy). Statistical analysis was
      done by a parametric test (ANOVA of single factor) (p<0.05). RESULTS: The
      activity of these enzymes was: Group I (n=5, basal GSHS). 2785,63 D.S. 419,51
      U/g; Group II (n=4, GSHS at 3 hours). 6053,50 D.S. 2788,84 U/g; Group III (n=4,
      GSHS at 48 hours). 7424,30 D.S. 997,47 U/g; Group IV (n=10, basal GSSGR). 150,86
      D.S. 24,40 mU/mL; Group V (n=7, GSSGR at 3 hours). 212,03 D.S. 53,30 mU/mL; Group
      VI (n=8, GSSGR at 48 hours). 210,84 D.S. 46,03 mU/mL. CONCLUSIONS: At retinal
      tissue, BSS Plus(R) intraocular irrigating solution increases GSHS activity
      without modifications of GSSGR levels. It seems to be related to the <<novo>>
      synthesis of glutathione.

PMID- 11967735
TI  - [Corneal descompensation in patients with endothelial compromise treated with
      topical dorzolamide].
AB  - PURPOSE: To investigate the possibility of corneal alterations in patients with
      long-term endothelial compromise with topical dorzolamide. MATERIAL AND METHODS:
      Retrospective descriptive study of 17 patients with penetrating keratoplasty and
      glaucoma associated with topical carbonic anhydrase inhibitor therapy, looking
      for coincidence with corneal alteration. RESULTS: Classified by ethiology, type
      of glaucoma and control, recording previous ophthalmological surgeries, evolution
      time, complications and rejection episodes. Seven patients suffered a corneal
      decompensation, in three of them there were signs of true reject but only four
      cases had edema at the beginning of dorzolamide treatment, one of them recovering
      after stopping dorzolamide. Risk factors were previous cataract surgery, mainly
      aphakia, filtering surgery and previous vitrectomy. CONCLUSIONS: Dorzolamide
      could have a potential negative effect on patients with endothelial compromise.

PMID- 11967736
TI  - [Glaucomatous damage pattern in swap in the early stages of glaucoma].
AB  - PURPOSE: To determine with Short-Wavelength Automated Perimetry (SWAP) the
      patterns of early glaucomatous damage and to compare frequency of diffuse defects
      to localized defects. METHODS: One hundred and sixty eyes from 83 ocular
      hypertensive subjects who met the selection criteria (intraocular pressure
      greater than 21 mm Hg and normal standard visual fields) were studied. SWAP was
      performed with a modified Humphrey Field Analyser. Total (TD) and pattern
      deviation (PD) probability maps were calculated to evaluate the pattern of visual
      field loss. RESULTS: The frequency of defects was higher in TD than in PD for all
      levels of defects (p<0.001). There was also a relative topographical distribution
      of glaucomatous defects. CONCLUSIONS: We documented the existence of
      predominantly diffuse visual field defects for all depth levels at early glaucoma
      stages.

PMID- 11967737
TI  - [Exenteration in benign orbital pathology: report of a case].
AB  - PURPOSE, MATERIAL AND METHOD: Orbitary exenteration is an indicated treatment for
      malignant and benign processes where special incidence of extension,
      uncontrollable pain, unrecoverable visual loss, cosmetic disfiguration, tendency
      to diffuse or persistent infiltration and malignancy potential have been
      observed. We report a case of a 22 year-old male from Senegal, presenting an
      isolated neurofibroma of the orbit of long evolution and great size.
      RESULTS/CONCLUSIONS: Treatment of this tumor is complete local resection. In this
      case an orbitary exenteration was performed due to size of the tumor and visual
      loss. We emphasize the need to treat these patients as soon as possible.

PMID- 11967739
TI  - [Cavernous sinus aneurysms. Treatment and evolution].
AB  - CASE REPORT: Two clinical cases of painful ophthalmoplegia from a cavernous sinus
      syndrome induced by carotid intracavernous aneurysm are presented. Two women
      presenting similar clinical patterns: total restriction of ocular movements,
      pthosis, alterations in the pupil and intense cephalalgia of sudden onset.
      Carotid aneurysms were found to be responsible for these clinical patterns. A
      carotid embolization was performed in one of the cases while a <<wait and see>>
      attitude was adopted for the other. DISCUSSION: Both cases showed similar
      favorable evolution, after a follow up period of one year. We concluded that in
      these cases a close collaboration with other specialties is required in order to
      adopt the most adequate therapeutic option.

PMID- 11967738
TI  - [Immunomediate scleritis in a patient with lepromatous leprosy].
AB  - CASE REPORT: A 55 year-old Spanish woman with a personal history of lepromatous
      leprosy treated for 10 years with anti-lepromatous triple therapy was referred to
      us presenting nodular scleritis in her left eye with no other clinical
      manifestations. Ophthalmological evaluation disclosed several inflammatory
      features in both eyes. Complementary tests performed were negative and the
      clinical picture was diagnosed as an immuno-mediated manifestation of leprosy. A
      favorable outcome was achieved with steroidal treatment. DISCUSSION: Scleritis
      and some immunomediated conditions may appear during the evolution of lepromatous
      patients whose disease may have been declared clinically cured.

PMID- 11967740
TI  - [Ophthalmologic vascular occlusions and oral contraceptives].
AB  - PURPOSE/MATERIAL AND METHOD: We present two cases of vascular ocular occlusion
      occurring during oral contraceptive use. Different contraceptive related risk
      factors are discussed. RESULTS/CONCLUSIONS: Although ocular complications are
      rare, they should be kept in mind since these drugs (contraceptives) are not
      recommended when vascular occlusion risk factors are present.

PMID- 11967741
TI  - [Why must the terms nyctalopia and hemeralopia be avoided?].

PMID- 11967743
TI  - [Regional congresses - goals, current scanding and perspectives].

PMID- 11967744
TI  - [Phylogeny of gas exchange systems].
AB  - Several systems of gas transport have developed during evolution, all of which
      are able to sufficiently supply oxygen to the tissues and eliminate the CO2
      produced by the metabolism, in spite of great distances between the environment
      and the individual cells of the tissues. Almost all these systems utilize a
      combination of convection and diffusion steps. Convection achieves an efficient
      transport of gas over large distances, but requires energy and cannot occur
      across tissue barriers. Diffusion, on the other hand, achieves gas transport
      across barriers, but requires optimization of diffusion paths and diffusion
      areas. When two convectional gas flows are linked via a diffusional barrier
      (gas/fluid in the case of the avian lung, fluid/fluid in the case of gills), the
      directions in which the respective convectional movements pass each other are
      important determinants of gas exchange efficiency (concurrent, countercurrent and
      cross-current systems). The tracheal respiration found in insects has the
      advantage of circumventing the convective gas transport step in the blood,
      thereby avoiding the high energy expenditure of circulatory systems. This is made
      possible by a system of tracheae, ending in tracheoles, that reaches from the
      body surface to every cell within the body. The last step of gas transfer in
      these animals occurs by diffusion from the tracheoles ("air capillaries") to the
      mitochondria of cells. The disadvantage is that the tracheal system occupies a
      substantial fraction of body volume and that, due to limited mechanical stability
      of tracheal walls, this system would not be able to operate under conditions of
      high hydrostatic pressures, i. e. in large animals. Respiration in an "open"
      system, i. e. direct exposure of the diffusional barrier to the environmental
      air, eliminates the problem of bringing the oxygen to the barrier by convection,
      as is necessary in the avian and mammalian lung, in the insects' tracheal system
      and in the gills. An open system is found in the respiration via the skin, which
      is of significance in some amphibians, but is limited by the thickness of the
      skin that constitutes a substantial diffusion path for O2 and CO2. The thick
      skin, on the other hand, provides mechanical protection as well as flexibility
      for the animals' body and helps avoid massive water loss via the body surface.
      The gills of fishes, in contrast, exhibit rather short diffusion distances, are
      located in a mechanically protected space, and the problem of water loss does not
      exist. The flows of blood and water occur in opposite direction (countercurrent
      flow) and this situation makes an arterial PO2 approaching the environmental PO2
      possible. A major disadvantage is constituted by the environmental medium since
      water contains little O2 compared to air and, to compensate this, much energy is
      expended to maintain a high flow rate of water through the gills. In the
      mammalian lung ("pool system"), the presence of a dead space and the rhythmic
      ventilation that replaces only a small fraction of the gas volume of the lung per
      breath, are responsible for an arterial PO2 (2/3 of the atmospheric PO2) that
      cannot reach the expiratory PO2. However, an advantage of this feature is the
      constantly high alveolar and arterial PCO2, which provides a highly effective
      H(+) buffer system in the entire body. The apparent disadvantage of the mammalian
      lung is avoided by the avian lung, which uses an extended system of airways to
      establish continuous equilibration of a part of the capillary blood with fresh
      air (cross current system), during inspiration as well as during expiration. In
      this system, arterial PO2 can significantly exceed expiratory PO2. A disadvantage
      here is the enormous amount of space taken up by the avian lung, in animals of 1
      kg body weight three times as much as taken up by the mammalian lung. All
      respiratory exchange systems considered here exhibit high degrees of optimization
      - yet follow highly diverse construction principles. There is no such thing as an
      ideal gas exchange system. The system that has evolved in each species depends to
      an impressive extent on environmental conditions, on body build and size, on the
      animal's patterns of movement and on its energy consumption.

PMID- 11967745
TI  - [New treatment option for gram-positive infections in critically ill patients -
      overview over linezolid].
AB  - INTRODUCTION: During the last decade, there has been an emergence of
      multiresistant Gram-positive bacteria in intensive care units. Oxazolidinones are
      a new class of antibiotics without cross-resistance to other antimicrobial
      agents, and linezolid was recently introduced as first oxazolidinone on the
      German market. In this overview, we summarize important data and discuss possible
      indications for linezolid in the treatment of infections in critically ill
      patients. ANTIMICROBIAL ACTIVITY AND PHARMACOLOGY: The antimicrobial spectrum
      comprises mainly Gram-positive bacteria, especially Staphylococcus aureus
      (including MRSA), coagulase-negative staphylococci, enterococci, and
      streptococci. Linezolid is mostly bacteriostatic and inhibits the bacterial
      protein synthesis at an early stage. Adults may receive 600 mg b.i.d.
      intravenously or p. o. About 30 % of the dose are excreted by the kidneys as
      mother compound and 50 % as metabolites. Dosage reductions are not necessary,
      even in severe renal impairment, but about one third of the dose is eliminated
      during dialysis. Overall, linezolid is well tolerated, but approximately 5 % of
      the patients may suffer from diarrhea or nausea and there have been a few reports
      about reversible myelosuppressive side effects. CLINICAL STUDIES: Linezolid has
      been compared to vancomycin for treatment of Gram-positive nosocomial pneumonia,
      and the clinical cure rates were 66.4 % and 68.1 %, respectively. Linezolid is
      highly active and bactericidal against pneumococci. The clinical cure rates for
      treatment of skin and soft tissue infections were 88.1 % with linezolid and 86.1
      % with penicillinase-stable penicillins. MRSA were excluded in this study, but it
      may be assumed from data in vitro that linezolid is equally effective against
      these bacteria. Data for the treatment of catheter-associated and other forms of
      bacteremias are mainly derived from the compassionate-use-program, where
      linezolid has been used in complicated cases, mainly after failure of standard
      therapy. The majority of infections was caused by multiresistant Enterococcus
      faecium and the clinical cure rates were approximately 80 %. COMMENT: The
      currently available data suggest that linezolid will serve as useful agent in the
      treatment of severe infections caused by multiresistant staphylococci and
      enterococci. Further studies are necessary to define the role of linezolid as
      first-line agent, e. g. in the treatment of central venous catheter infections.
      In light of the severe prognosis of pneumonias caused by MRSA, studies on the
      combination of linezolid and vancomycin are warranted. Despite the low level of
      resistance, it seems prudent not to use linezolid as first line agent in the
      treatment of uncomplicated infections, as long as effective standard antibiotics
      are available.

PMID- 11967746
TI  - [The abbreviated mental test in a German version for detection of postoperative
      delirium].
AB  - OBJECTIVES: Delirium is the most common acute organic psychosis postoperatively,
      and occurs more frequently in the elderly than anticipated. The abbreviated
      mental test (AMT) is a widely used cognitive test in Great Britain. The present
      study assessed the AMT in a German version for diagnosis of postoperative
      delirium. METHODS: 40 patients (older than 65 years), scheduled for total knee or
      hip replacement, were tested repeatedly for delirium according to the ICD-10.
      These patients were investigated with the AMT simultaneously by a second
      investigator. RESULTS: Delirium was present in four orthopaedic patients (10 %)
      and was diagnosed correctly in these patients by the AMT. All but one patient
      without delirium showed no deterioriation in AMT score. CONCLUSION: As in Great
      Britain, the AMT in its German version is useful in diagnosing delirium. We
      recommend the use of the AMT preoperatively in elderly patients at risk for
      delirium.

PMID- 11967747
TI  - [Experiences with the psychometric system combitest in the evaluation of the
      postnarcotic arousal period].
AB  - Since the introduction of new German health legislation, operations formerly
      performed on an in-patient basis have been transferred to the out-patient sector.
      Due to this development evaluating the postnarcotic arousal period has become
      increasingly important. Vigilance, reactivity and state of health determine a
      patient's well-being and time of discharge after an operation and consequently
      influence economical and legal issues. Former studies investigating the arousal
      period have mainly focused on patient interviews and assessment of patients by
      staff. The aim of our study was to objectivize postnarcotic vigilance and
      reactivity (critical flicker fusion frequency and multiple choice reaction) using
      neurophysiological monitoring (psychometric system Combitest 2: CFF, EWR, MWR).
      The applied methods have been defined as valid, reliable and sensitive tools to
      investigate this question. Inter-individual and gender-specific differences as
      well as variations due to the type of anaesthetic employed can be detected. The
      study participants assessed the test battery's practicability and overall
      described this method as easy to use. Vigilance (CFF), basic and complex
      sensomotor reactivity (performance in simple and multiple choice tests) were
      restored after a postanaesthetic phase of 90 minutes (narcotics applied:
      isofluran and propofol). The results show that the use of modern anaesthetics
      does not justify the current medical and legal claim to 6 hours of
      postanaesthetic observation. The computer-supported psychometric system Combitest
      2 has recently been used to assess the arousal phase after application of
      different types of anaesthetical procedures (TIVA, volatile, balanced) and has
      been found to be superior to parameters traditionally used to assess discharge
      criteria (time until patient opens eyes, orientation concerning time and
      location, time spent in postanaesthetic recovery room). Besides employing our
      study methods, subjective factors such as well-being and pain sensation should
      also be evaluated when determining the time of a patient's discharge.

PMID- 11967749
TI  - [Severe mediastinal emphysema after temporal gunshot with a gas revolver].
AB  - Injuries after a close contact gunshot with clear or tear gas cartridges can lead
      to severe and life threatening complications. The high pressure of the gas may
      damage soft tissue, bones and organs. This mechanism is able to cause mediastinal
      emphysema, rupture of upper and lower pharyngeal, esophageal and tracheal
      structures far away from the initial trauma with diagnostic findings which are
      may be difficult to interpret. This case report presents a mediastinal emphysema
      in a 17 year old man following a temporal shot with a gas revolver. The
      diagnostics, focussed on CT and X-ray imaging, and the therapeutic concept of
      such cases will be discussed.

PMID- 11967748
TI  - [Motor function during patient-controlled analgesia via a lumbar epidural
      catheter after major abdominal surgery. Ropivacaine-sufentanil vs. bupivacaine
      sufentanil].
AB  - INTRODUCTION: The aim of the present study was to investigate postoperative
      motoric impairment during patient-controlled analgesia after major abdominal
      surgery with ropivacaine-sufentanil and bupivacaine-sufentanil via a lumbar
      epidural catheter. METHODS: After approval of the local ethics committee, 40
      patients scheduled for major lower abdominal surgery were randomly allocated to
      receive bupivacaine 0.25 % or ropivacaine 0.2 %, both with sufentanil 2
      microgram/ml in a double blind manner. General anaesthesia (midazolam, etomidate,
      fentanyl, vecuronium, and desflurane in N2O/O2) and postoperative management of
      the patients were standardised. Postoperatively, the motoric function and ability
      for active early mobilisation was examined clinically (application of the Bromage
      scale, ability to leave the bed and ability to walk). Reduction of muscular force
      of the legs was measured postoperatively using a scale and compared with
      preoperative baseline values. To ensure a similar level of analgesia, a 10-cm
      visual analogue scale was applied at rest and while coughing. RESULTS: The two
      groups did not differ with respect to the demographic data and postoperative
      levels of analgesia. Less reduction of motoric function at rest was observed in
      the ropivacaine group (p = 0,044). However, this did not lead to an increased
      ability to get up from bed (p = 0,57) or to walk around (p = 0,17). A high number
      of patients did not meet the requirements for early ambulation. Almost half of
      the patients of both groups were unable to leave their beds in the morning of the
      first postoperative day. On the second postoperative day about 25 - 30 % of the
      patients could not walk even when support was applied. Furthermore, median
      reduction (10th/90th percentile) of muscular strength was reduced to 50 % (37
      %/76 %) in the ropivacaine group and to 48 % (31 %/61 %) in the bupivacaine group
      compared with preoperative values. DISCUSSION: While quality of analgesia was
      similar, mobility of the legs at rest is better preserved with ropivacaine 0.2 %
      than with bupivacaine 0.25 %. However, despite the fact that high dose sufentanil
      was added to both local anaesthetics, there was marked motoric impairment in both
      groups probably due to the lumbar site of the epidural catheter. This was
      associated with an unacceptable high incidence of patients unsuitable for early
      postoperative mobilisation.

PMID- 11967751
TI  - In vitro analysis of esophageal atresia using a whole-embryo culture system.
AB  - BACKGROUND/PURPOSE: Administration of Adriamycin to pregnant rats leads to the
      development of esophageal atresia with tracheo-esophageal fistula. This defect
      arises from failure of the trachea to develop normally from the primitive
      foregut; instead,the upper foregut differentiates into trachea, then continues to
      the lower esophageal segment as a tracheo-esophageal fistula. Our aim was to
      explore the possibility of growing Adriamycin-exposed embryos using a whole
      embryo culture technique and to determine whether or not esophageal atresia with
      tracheo-esophageal fistula could be prevented in an Adriamycin-treated rat model.
      METHODS: Rat embryos were exposed to Adriamycin in utero on days 6 - 9 of
      gestation, removed on day 10 and grown in vitro as described by New (11) for 48
      hours using 100% serum from animals not exposed to Adriamycin. RESULTS: Thirty
      Adriamycin-exposed embryos were grown in vitro using normal serum. Histologic
      assessment of tracheo-esophageal development showed that 14 embryos had normal
      development, while 16 developed esophageal atresia. CONCLUSIONS: Growth of
      Adriamycin-exposed embryos was successful using "whole-embryo culture technique";
      abnormal tracheo-esophageal development could in some cases be altered by
      removing the embryos at day 10 and exposing them to normal serum for 48 hours.

PMID- 11967752
TI  - Polyunsaturated phosphatidylcholine lowers collagen deposition in a rat model of
      corrosive esophageal burn.
AB  - Esophageal strictures are characterized by excess deposition of collagen in the
      esophageal wall. Polyunsaturated phosphatidyl-choline (PPC) stimulates collagen
      breakdown in experimental models of liver cirrhosis and colitis. This study was
      done in order to investigate the therapeutical effect of PPC in preventing
      esophageal strictures due to alkali-induced esophageal burns in rats. Fifty-five
      albino rats were divided into four groups as follows: control group (Group A, 10
      rats), rats with sham operation and treated with saline (Group B, 15 rats), rats
      with esophageal burns only (Group C, 15 rats), and PPC-fed rats with esophageal
      burns (Group D, 15 rats). A standard esophageal burn was produced as described by
      Gehanno. PPC was administered orally to Group D rats in doses of 100 mg/day for
      four weeks. All animals were sacrificed on the 28th day of the experiment.
      Hydroxyproline levels in esophageal tissue was determined in each rat, and
      histopathologic evaluation was performed for each group. Hydroxyproline levels
      were significantly lower in the PPC-fed rats than in the rats with pure
      esophageal burns (p < 0.001). Histopathologically, collagen deposition in the
      submucosa and tunica muscularis was lower in Group D rats (PPC-fed rats with
      esophageal burn) than Group C rats (pure esophageal burn) (p < 0.05). As a result
      of our study, we concluded that PPC has an ameliorating effect on stricture
      formation after alkali-induced corrosive esophageal burns in rats.

PMID- 11967753
TI  - Abdominal cystic lymphangiomas in children: presurgical evaluation with imaging.
AB  - Cystic lymphangiomas are benign vascular tumors which are most often seen in
      young children. They are considered to be congenital malformations stemming from
      sequestration of lymphatic tissue. The authors report 15 cases of abdominal
      location and detail the findings of imaging in the etiologic and topographic
      diagnosis of these lesions. The initial incidents were essentially the discovery
      of a palpable abdominal mass, and more rarely, an acute gastrointestinal
      complication. There was also one case of prenatal diagnosis. Plain films provide
      only indirect signs related to the displacement of neighboring organs.
      Ultrasonography permits the etiologic diagnosis by showing an often voluminous,
      septated cyst. The intra- or retroperitoneal location of the lesion is sometimes
      difficult to determine by sonography, in which case CT scanning is usually
      adequate. For abdominal locations, percutaneous sclerosis is not available, and
      surgical removal is the only treatment for this disorder. The topography of the
      lesion and the involvement of retroperitoneal structures is important to
      determine.

PMID- 11967754
TI  - The distal pouch in esophageal atresia -- to dissect or not to dissect, that is
      the question.
AB  - Long-gap esophageal atresia remains a difficult problem for the pediatric surgeon
      and reconstruction using the native esophagus is considered to be superior to any
      interposition procedure. Because of esophageal segmental blood supply and
      vascular vulnerability of the distal esophageal pouch in the short term and its
      motility disorder in the long term, surgeons are reluctant to perform extensive
      esophageal dissection. However, ascending and descending branches of esophageal
      vessels converge along the anterolateral and posterolateral aspects of the
      esophagus. This arrangement allows for dissection and mobilization of the distal
      pouch without necessarily causing vascular impairment. Extensive dissection of
      the distal pouch was advocated by Robert Gross over fifty years ago. More
      recently, circular myotomy of the distal pouch has been performed. However,
      manometric studies showed that prior to surgical repair, peristalsis of the upper
      and lower esophageal pouch was synchronized, while after surgery this
      coordination was clearly defective. Furthermore, in the adriamycin-induced rat
      model, inherent abnormalities in the course and branching pattern of the vagus
      nerves in the lower esophagus have been demonstrated. Significant abnormalities
      of the intramural nervous components involving both the excitatory and inhibitory
      nerves, and elevated levels of S100 and galanin in the lower esophageal pouch
      could explain an inborn motility disorder. The selective injury of minor vagal
      branches in experimental animals also alters esophageal peristalsis. In
      conclusion, given that the native esophagus is still considered the best
      alternative for reconstruction of esophageal atresia, when indicated, gentle but
      extensive dissection of the lower esophageal pouch seems to be preferable,
      keeping in mind the possibility of vascular compromise and the inevitability of
      motility disfunction.

PMID- 11967755
TI  - One-trocar transumbilical laparoscopic-assisted appendectomy in children: our
      experience.
AB  - The authors report their experience with one-trocar transumbilical laparoscopic
      assisted appendectomy (TULAA). From January 1998 to June 2000, 150 patients
      underwent appendectomy using this technique. Ages ranged from 2.5 to 17.4 years.
      The procedure was completed using only one trocar in 116 cases (77.3%); in 28
      patients (18.7%) one or two additional cannulas were needed. Conversion to open
      surgery became necessary in 6 cases (4%). Mean operative time was 35 minutes,
      mean hospital stay 3.5 days. There were no major complications and no mortality
      in this series. The advantages of a one-trocar appendectomy compared with open
      surgery are the same as those reported for conventional laparoscopic
      appendectomy: i.e., excellent exploration of the abdominal cavity, the
      possibility of discovering extra-appendiceal lesions, easy and rapid localization
      of the appendix and a shorter hospital stay. The additional advantages of TULAA
      compared with conventional laparoscopic appendectomy are a low rate of
      intraoperative incidents, minimal scarring, less postoperative pain and a more
      rapid return to unrestricted activities.

PMID- 11967758
TI  - Urodynamic findings of posterior urethral valve patients.
AB  - The most frequently observed cause of obstructed bladder in children is the
      posterior urethral valve (PUV). In this report, we analysed the urodynamic
      findings of 26 patients whose valves were fulgurated 12.6 months previously
      (range: 2 days - 8 years,after the fulguration). The mean age of the patients at
      the time of the procedure was 4.5 years (range: 2 months -13 years). Bladder
      capacity was decreased in 15, increased in 6, and normal in 5 patients; hypo
      compliance was observed in 13, hyper-compliance was observed in 4, and normo
      compliance was observed in 9 children. Generally, hypo-compliance and decreased
      bladder capacity was more frequent in patients younger than 4 years of age. There
      were 10 patients with instable detrusor contractions(IDC) and high residual urine
      was present in 8 patients. Eight patients developed chronic renal failure and 6
      of these patients had high residual urine. All the patients who required bladder
      augmentation during follow-up were the ones treated after 2.5 years of age; 4 of
      these 5 patients had hypo-compliance and low bladder capacity on urodynamic
      studies. In conclusion, all patients with PUV had pathological urodynamic
      findings that could change with age, and early relief of the infravesical
      obstruction could have an improving effect on bladder function. Urodynamic
      investigations may help us to design the proper treatment according to the
      bladder function.

PMID- 11967757
TI  - Management of the primary obstructed megaureter (POM) and indication for
      operative treatment.
AB  - Presented is the diagnostic and therapeutic management of the primary obstructed
      megaureter (POM). 42 patients presented with 53 ureteral units (UU) of POM (5
      females, 37 males, 36 neonates and 6 children aged 3 to 8 years). Of the 53
      megaureters 10 UU (19%) were on the right and 27 UU(51 %)were on the left. 8
      patients (19%)with 16 UU (30%)showed a bilateral abnormality. In 41% of the
      patients, hydronephrosis had been discovered by prenatal ultrasound. All patients
      were evaluated postnatally by ultrasound (US), voiding cysturethrogram (VCUG),
      intravenous pyelogram (IVP) and diuresis renogram (MAG-3) (DR). Due to the
      percentage of urinary drainage,the renogram results were classified into
      different categories:no obstruction, functional obstruction, equivocal and
      obstruction. A partial renal function was also calculated. Follow-up of the
      patients ranges between 5 to 48 months (mean: 22.1). All patients underwent
      serial US and serial DR were obtained in 36 patients. Initially, 9 (17%) UU
      showed a functional obstruction, 34 (64.2%) an equivocal and 10 (18.8%) an
      obstructive urinary drainage pattern. 2 kidneys showed a significant decreased
      partial function of 20, respectively 26%. Surgery was performed in an initial im
      paired renal function with an obstructive pattern or in cases with normal
      function and at least equivocal urinary drainage pattern with no improvement or
      deterioration of the urinary drainage and/or function in the follow-up.
      Considering these criteria, 5(9.6%) patients needed surgery. No loss of kidney
      function has been observed in follow-up. DR is the most valuable diagnostic tool.
      Criteria interpreting the results are demonstrated in this article.

PMID- 11967756
TI  - Neurogenic appendicopathy in children.
AB  - BACKGROUND: In a prospective multicenter study, we could show that neurogenic
      appendicopathy is a histological entity. This study compares the general and the
      pediatric population with respect to clinical presentation and incidence of
      neurogenic appendicopathy (NA). METHODS: Included were patients that underwent
      appendectomy for suspected appendicitis, excluded were patients younger than 6
      years and patients with missing data. Neurogenic appendicopathy was diagnosed by
      S-100 immunochemistry and/or haematoxylineosin (H.E.) staining. Two age groups (<
      or = 14 y and > 14 y) were compared with respect to the frequency of NA. RESULTS:
      In only four cases out of 84 children (4.8%) did we find neurogenic
      appendicopathy compared to 48 patients (24.2 %) out of 198 adolescents and
      adults. In the subgroup with negative appendectomy, the frequency of NA was 16.7%
      (< or = 14 years) and 56.6% (> 14 years). A clinical differentiation between
      neurogenic appendicopathy and acute appendicitis was not possible because of the
      small sample size. CONCLUSION: Neurogenic appendicopathy is a very rare
      histopathological entity in children. History and clinical examination do not
      make it possible for us to differentiate preoperatively between acute
      appendicitis and neurogenic appendicopathy.

PMID- 11967759
TI  - Xanthogranulomatous pyelonephritis in children: diagnostic and therapeutic
      aspects.
AB  - BACKGROUND: Xanthogranulomatous pyelonephritis (XGP) is an uncommon chronic,
      inflammatory disease of the kidney. Etio-pathogenesis, diagnosis and management
      of pediatric XGP is still obscure due to the limited number of cases. Therefore,
      a retrospective clinical study was carried out to present an updated picture of
      the entire spectrum of pediatric XGP based on our 30 years' experience covering
      one of the largest non-collected series treated in a single medical center.
      METHODS: Records of children who were treated for XGP in our unit from 1970 to
      1999, inclusive, were reviewed retrospectively. Information recorded for each
      patient included age, sex, past medical history, clinical characteristics,
      diagnostic procedures,treatment methods, histopathologic findings and outcome.
      RESULTS: 17 children with a mean age of 6.6 +/- 0.8 years, consisting of 15 males
      and 2 females, were treated for XGP. Eight patients had a urological disease
      history and 4 of them underwent surgery for urinary calculi and exstrophia vesica
      repair. The most common presenting symptoms were abdominal pain, fever,weight
      loss and anorexia. Palpable flank mass was the most common physical examination
      finding. Left and right kidneys were involved in 10 and 7 patients, respectively.
      Diagnostic procedures were intravenous pyelography, retrograde pyelography,
      ultrasound scan and computerized tomography (CT). Renal calculi and/or
      calcifications and non-functioning kidney were the most frequent findings in
      radiologic investigations. By combining all these investigations, the
      preoperative diagnoses were XGP (n = 2), renal and/or perirenal abscess (n = 5),
      psoas abscess(n = 2), non-functioning kidney due to recurrent pyelonephritis(n =
      4), Wilms' tumor and/or renal clear-cell carcinoma (n = 4). XGP was correctly
      diagnosed in only two patients based on cr findings. Drainage of the renal or
      psoas abscess was performed in 8 patients as an initial procedure (surgical
      drainage in 6 and ultrasound-guided percutaneous drainage in 2 patients).
      Surgical procedures included nephrectomy (n= 13), partial nephrectomy (n=2),
      nephrectomy and diversion of reno-colic fistula(n= 1), and renal biopsy and
      nephrostomy (n= 1). Operative and postoperative complications were colonic
      perforation (n= 3) and wound infection (n = 3). Complications were noted only in
      patients who underwent nephrectomy without initial drainage procedures.
      Histopathologic examinations showed diffuse and focal XGP in 14 and 3 patients,
      respectively. CONCLUSION: XGP should be included in the differential diagnosis of
      all children presenting with perirenal or psoas abscess, renal mass and/or non
      functioning kidney associated with/or without urolithiasis. Clinical awareness
      and a high index of suspicion is required to achieve the correct preoperative
      diagnosis and appropriate management. CT seems to be the most valuable imaging
      method for the diagnosis. We strongly recommend percutaneous drainage of the
      abscess and adjunctive antibiotic therapy prior to nephrectomy to avoid
      complications. Complete nephrectomy is the proper treatment for the diffuse form
      whereas frozen section biopsies followed by partial nephrectomy are mandatory for
      the proper treatment of focal disease.

PMID- 11967760
TI  - Acrocephalosyndactyly -- the coalesced hand.
AB  - Described nearly a century ago, Apert's Syndrome (A.S.) is a rare disorder
      affecting 1/80,000 children, the mode of inheritance is autosomal dominant or
      sporadic. Apart from the more obvious skull malformations, extensive and complex
      hand deformities create several problems for the child's interaction with its
      environment, preventing normal intellectual development and generating
      psychological problems as severe as those caused by the craniofacial
      abnormalities. The deformities seen here are some of the most complex of all
      congenital hand malformations. Between January 1987 and January 1999, 71 children
      presenting with hand syndactyly were treated at the Hospital de Dona Estefania
      (H.D.E.), a total of 177 syndactylies. Of those, 51 had no associated illnesses,
      14 had other conditions and six had A.S. All six cases were sporadic; one child
      had a cleft palate and another suffered from epilepsy. The timing at which the
      various surgeries were performed was diverse, however, there has been a recent
      trend towards earlier interventions in order to obtain a functional hand before
      the age of two. Aesthetic results vary a lot depending on the complexity of the
      lesions and we sometimes accept a three or four-digit, but functional hand. We
      achieved hands with a function of 40 to 65 % in all our patients before school
      age. Due to A.S.' rarity, an effective use of resources and good results can only
      be obtained in a specialised centre with a multidisciplinary team.

PMID- 11967761
TI  - Twins with oesophageal atresia and the CHARGE association.
AB  - Twins are rarely concordant for oesophageal atresia and tracheo-oesophageal
      fistula. Such a case is presented and their similar associated anomalies
      described. The CHARGE association is considered as a possible diagnosis and the
      aetiological implications considered.

PMID- 11967762
TI  - Diffuse neonatal hemangiomatosis associated with Simpson-Golabi-Behmel syndrome:
      a case report.
AB  - Diffuse neonatal hemangiomatosis (DNH) is a rare disorder characterized by
      multiple cutaneous and visceral hemangiomas that usually presents in newborns and
      has a high mortality rate. While previously reported cases of DNH describe
      multiple cutaneous hemangiomas, we present a patient with a single hemangioma of
      the ear, who also had DNH of the central nervous system and visceral organs.
      Furthermore, in this report we present a new constellation of findings, namely, a
      Simpson-Golabi-Behmel syndrome (SGBS). The practical implication on the basis of
      the experience with our patient is the need to ensure adequate diagnostics for
      patients with large hemangiomas as well as for patients with multiple cutaneous
      hemangiomas, because DNH also can occur in single hemangiomas in rare cases.

PMID- 11967763
TI  - Management of seat-belt syndrome in children. Gravity of 2-point seat-belt.
AB  - We present our experience with a management of seat-belt syndrome in three
      children and draw particular attention to the severity of two-point fixation seat
      belt injuries after a motor vehicle accident with 5 passengers whose vehicle was
      struck head-on by an oncoming vehicle. The parents were sitting in front, Adeline
      had a 2-point lap seat-belt, the 2 other children had 3-point seat-belts. The
      parents both had humerus fractures. The 4-year-old brother suffered a cervical
      and abdominal trauma with renal and splenic contusions and intestinal
      perforations. Adeline suffered multiple injuries, notably to the head, spine and
      abdominal viscera with erosions at the site of lap-seat-belt contact. The spinal
      injury was an L2 angular Chance fracture associated with paraplegia on the 7th
      day. Operative findings included a transverse tear of the left rectus abdominus
      muscle, an incomplete transection of the stomach and perforation of the ileum.
      The injuries were ultimately fatal. Given associated abdominal pain, skin
      erosions at the site of seatbelt contact, spinal fracture, and rectal muscle
      disruption apparent on emergency laparotomy, early diagnosis is important for
      better prognosis.

PMID- 11967764
TI  - Pitfalls in diagnosing carpal tunnel syndrome.
AB  - The aim of this paper is to point out the differential diagnosis be-tween a thumb
      hypoplasia type 1/11 and a carpal tunnel syndrome. Both syndromes have symptoms
      in common. Two children and an adult with hypoplastic thumbs were sent to our
      department with the diagnosis carpal tunnel syndrome. In both children, the
      diagnosis was changed after an exact history and examination, and in one child an
      opponensplasty was done. The adult patient had already been operated
      unsuccessfully for a carpal tunnel syndrome elsewhere and again at our
      department. The exact diagnosis was only made after the second operation,when an
      extended questioning was done. This shows how important a careful history taking,
      an exact clinical examination, X-ray examinations of both hands, knowledge of
      type 1/11 hypoplasia, and finally electroneurography and sonography are important
      for a correct diagnosis.

PMID- 11967766
TI  - [Words of acknowledgement and friendship on the 65th birthday anniversary of
      professor dr. Jan helms].

PMID- 11967768
TI  - [The Wurzburg Ear Forms: a system to document surgery and follow-up evaluation].
AB  - BACKGROUND: About a decade ago a PC based system to document surgery and follow
      up evaluation was installed. At that time the wide spread DOS systems provided
      only inputs via the keyboard. However, we believed that to assure the system
      would be accepted by the user, a graphical user interface would be necessary.
      Such an interface provides greater user-comfort and ensures the validity of
      entered data. METHODS: A simple graphical platform was installed, which provided
      all the necessary functions without being too complex. Several forms were
      designed for data collection. The first form implemented was designed for ear
      surgery. It comprises 356 items. The relevant data in the form are selected by a
      mouse click from possible alternatives. Although a large number of items are
      provided, it takes only one to two minutes to fill in the form. RESULTS: At
      present, September 2001, the database contains 10 453 records related to ear
      operations, 9633 preoperative audiograms and the results from 16 140 follow up
      evaluations. A special language and an interpreter for analyzing the data were
      added to complete the system. CONCLUSIONS: The large number of cases stored in
      the database allows data analysis with a high level of statistical confidence for
      any conclusions based upon the data. It also allows investigations of the
      simultaneous influence of a large number of variables on the results.

PMID- 11967767
TI  - [Results after rebuilding the ossicular chain using the autogenous incus, ionomer
      cement-and titanium implants (tympanoplasty type III)].
AB  - BACKGROUND: A defective ossicular chain can reliably be reconstructed with
      standardized techniques using e. g. modern alloplastic materials. The comparison
      of clinical and functional results have proved its worth. Prospective clinical
      trial as well as collecting and evaluating relevant intraoperative and
      postoperative findings may be helpful to find the appropriate bone substitute in
      each case when rebuilding middle ear structures. METHOD: In 354 middle ears (332
      patients) the defective or destroyed ossicular chain was rebuilt with the
      carefully trimmed autogenous incus (n = 83), with ionomer-cement implants (n =
      100) and with titanium prostheses (n = 171). The follow-up of the earmicroscopic
      findings and middle ear function extended over a period of 1.5 years
      postoperatively on an average (min. 3 months, max. 6 years). The modified
      otologic record form named "Wurzburger Ohrbogen" was used for preoperative and
      operative data, the "Ohrnachsorgebuch" for the postoperative follow-up. RESULTS:
      Using incus the air bone gap was improved up to 15 dB in the main speech area.
      Thus the average remaining conduction deficit was less than 10 dB. The "taking"
      of ionomer based cement prostheses and titanium prostheses was equally good. The
      cement implants showed a tendency to protrusion (n = 3), 2 titanium implants were
      extruded. The air bone gap decreased about 10 to 35 dB using titanium total
      prosthesis and about 15 to 20 dB using ionomer-cement total prosthesis. The
      remaining air bone gap with titanium implants was slightly less than with the
      ionomer-cement PORP (10-15 dB). The air bone gap using the titanium TORP was
      diminished in a reach of 10 to 35 dB, with the ionomer cement prosthesis between
      15 to 20 dB. The remaining gap in the main speech area was slightly favorable to
      titanium (less than 15 dB) compared with the ionomer-cement TORP. Comparing
      higher frequencies the air bone gap of titanium was recognizable due to its light
      weight, but less impressive than expected. Revision surgery (n = 50) has to be
      performed by reason of cholesteatoma (n = 9), adhesive process (n = 8),
      dislocation of alloplastic prostheses (n = 8) and because of proposed "second
      look" (n = 14). CONCLUSIONS: Compared with other materials autogenous implants
      used for reconstruction of the incus have proved their value, however a
      deterioration of the sound transmission may develop in the long run. The middle
      ear compatibility of ionomer-cement implants is similar to titanium implants. The
      functional results of the titanium implants seem to be slightly superior.

PMID- 11967769
TI  - [Titanium as a material for ossicular replacement - basic aspects and clinical
      application].
AB  - BACKGROUND: The use of titanium as a biomaterial in ossicular chain
      reconstruction is increasing. The situation for integration of biomaterials is
      more difficult in the semiopen implantation site middle ear than in other parts
      of the body. Important for integration is the contact of the biomaterial's
      surface toward proteins. Studies of the integration in living tissue still have
      to be performed in animal experiments. Morphological examinations of explanted
      prostheses after clinical use complete the picture of an ossicular replacement
      material. METHODS: Preclinical studies where performed to compare the adsorption
      behaviour of titanium, stainless steel and aluminum oxide toward radioactive
      marked albumin and native collagen type I. An animal model in the rabbit was
      performed to study the integration of titanium in the middle ear morphologically.
      Middle ear prostheses removed during revision surgery were studied as well.
      RESULTS: Titanium showed an adsorption amount of 360 microgram/cm(2), stainless
      steel of 230 microgram/cm(2) and aluminum oxide of 500 microgram/cm(2) out of an
      albumin solution of 400 mg/ml. Comparing desorption the mean loss was 16 % for
      titanium, 21 % for stainless steel and 23 % for aluminium oxide. Reassembled
      collagen fibrils could be detected after adsorption in collagen type I solution
      by means of scanning electron microscopy. Morphological studies in animal
      experiments showed regular healing after implantation. Explanted prostheses from
      humans did not show any cellular signs of repulsion. CONCLUSION: The results of
      preclinical studies and clinical use demonstrate titanium as a useful material
      for ossicular reconstruction in middle ear surgery.

PMID- 11967770
TI  - [Histomorphometric assessment of spiral ganglion neurite outgrowth in vitro].
AB  - BACKGROUND: During the last years, various groups of growth factors have been
      identified to influence spiral ganglion cell survival and neurite extension in
      the mammalian cochlea. To evaluate and compare the effects of different growth
      factors, a precise histomorphometrical analysis of neurite outgrowth patterns has
      to be applied. The here presented technique is compared to already published
      methods, that only approximately estimate the neurite length. METHOD: A software
      has been developed to analyse digitalised scans of spiral ganglion cells and to
      measure the length of the neurites. Therefore, the neurites are being separated
      in any given number of straight lines. The totals of these lines can then be
      added like a polygon. This polygon method was compared to a semi-quantitative
      procedure in which the neurite length was determined by concentric circles that
      were crossed by the neurites in a certain distance. The accuracy of both methods
      was analysed. Both methods were performed in 20 specimen of neonatal rat spiral
      ganglion cells after in vitro stimulation with neurotrophic factors. RESULTS: The
      semi-quantitative method has shown to involve a systematic error between +/- 10
      to 15 %. The polygon method, on the contrary, has a systematic error of around +/
      1 %, which admits much more accurate measurement of spiral ganglion neurite
      outgrowth. CONCLUSION: With the described polygon method, spiral ganglion neurite
      growth patterns in cell culture studies can be characterised more precisely and,
      thus, helps to better differentiate the action domain of neurotrophic factors.

PMID- 11967771
TI  - [Wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase influences
      neurotrophin-induced spiral ganglion neurite growth].
AB  - BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) is considered to be an important
      enzyme in cell signaling, mediating certain aspects of neurotrophin signals from
      the cell surface receptor to the nucleus. METHODS: The participation of PI3K in
      the mediation of neurotrophin-induced effects in the spiralganglion (SG) of
      neonatal rats was investigated in vitro. SG explants were stimulated with
      neurotrophin (NT)-3 and treated with Wortmannin, a specific inhibitor of PI3K.
      After fixation and immunhistochemical staining, the growth of the SG neurites was
      evaluated. RESULTS: Stimulation with NT-3 lead to significant increases in number
      and length of neurites, when compared to non-stimulated controls. Treatment of NT
      3 stimulated SG explants resulted in a dose-dependent reduction of both
      parameters, whereas the neurite growth of non-stimulated control explants was not
      significantly influenced by the incubation with Wortmannin. CONCLUSIONS: The
      results demonstrate that neurotrophin-induced neurite growth from SG explants can
      be modulated with the PI3K inhibitor Wortmannin and indicate that PI3K is a key
      enzyme in the mediation of NT-3 effects in cochlear neurons. These observations
      together with results of previous studies suggest that the activation of PI3K as
      well as Ras and MEK are essential for neurite growth in cochlear neurons. Further
      knowledge of cell signaling mechanisms influencing SG neurite growth could lead
      to new therapeutical strategies for the treatment of inner ear diseases.

PMID- 11967772
TI  - [The effects of quinine on active motile responses and fine structure of isolated
      outer hair cells from the Guinea pig cochlea].
AB  - BACKGROUND: Large doses of quinine (as well as of salicylate) are known to
      produce reversible hearing loss and tinnitus. Cochlear outer hair cells seem to
      be the common site for the ototoxic effect of both drugs. METHODS: Isolated outer
      hair cells from the guinea pig cochlea were exposed to ototoxic doses of quinine
      hydrochloride (0.05-1.5 mmol/l). The cells were examined using tight-seal whole
      cell recording techniques and transmission electron microscopy. RESULTS: Quinine
      exposure led to a hyperpolarization followed by a depolarization of the hair
      cells' membrane potential. It also caused a diminution of evoked rapid motile
      responses that was more apparent in response to hyperpolarizing than to
      depolarizing pulses. These effects were largely dose dependent and reversible.
      Ototoxic doses of quinine were not found to induce changes in turgor, shape or
      fine structure of outer hair cells such as those reported with ototoxic doses of
      salicylates in vitro. CONCLUSIONS: The present in vitro findings show that
      quinine (as well as salicylate) directly and reversibly affects cochlear outer
      hair cells. They also indicate that the underlying mechanisms of quinine
      ototoxicity are considerably different to that of salicylate although both
      substances clinically lead to identical symptoms.

PMID- 11967773
TI  - [Universal newborn hearing screening program in Wurzburg. Experience with more
      than 4000 newborns and the influence of non-pathological factors on the test
      results].
AB  - BACKGROUND: The BERAphon(R) method employing a special headphone and the time
      course step-stimulus algorithm offers a quick and reliable tool for universal
      hearing screening in newborns. An ABR-based universal newborn hearing screening
      program has been established in Wurzburg since August, 1997. Until August 2001,
      4115 newborns have undergone primary and/or control-screening with the
      BERAphon(R). The validity of this method was further examined by testing the
      effects of non-pathological factors such as gender, age, Apgar score, pH value of
      the umbilical cord, head circumference and duration of pregnancy on the ABR wave
      V latency in 415 infants. RESULTS: Out of 3930 infants who were primary screened,
      27 infants were diagnosed to have hearing loss. Furthermore, hearing loss was
      detected in 35 out of 185 infants referred for control screening. Non
      pathological factors showed a minor effect on the test results. Apgar score,
      gender or chronological age did not have any significant effects on the latency
      of wave V. Duration of pregnancy, pH value of the umbilical cord or head
      circumference showed a significant but weak correlation with wave V latency.
      CONCLUSIONS: Only non-pathological factors related to maturation had a minor
      effect on ABR measurements using the time-course-step-stimulus algorithm. The
      BERAphon(R) method has proven to be a reliable, robust method giving information
      related to the hearing threshold and accordingly can be used reliably for hearing
      screening in newborn infants.

PMID- 11967774
TI  - [The Wurzburg questionnaire for assessing the quality of hearing in CI-children
      (WH-CIK)].
AB  - BACKGROUND: The goal of this study was to compare the auditory behaviour of
      bilaterally implanted children while using both CIs to their auditory behaviour
      during the time when they were using one CI. METHODS: For this purpose a
      questionnaire looking at different aspects of hearing such as hearing in
      background noise, in complex listening situations and directional hearing was
      developed. The questionnaire was completed by the parents of 28 bilaterally
      implanted children. They were instructed to state their judgement on the
      behaviour of their children. The parents scaled their judgements using a method
      of extended category scaling similar to that applied in the loudness scaling with
      the Wurzburg hearing field (WHF). Each of the five verbal categories was
      subdivided into 10 numerical subdivisions, so that the parents were able to
      express judgements lying between the different categories. RESULTS: Eight out of
      eleven items showed that hearing with bilateral CIs was significantly better than
      with one CI (p < 0,003). The two items, which did not show a significant
      difference between the two conditions were those related to the interest in
      auditory rehabilitation and to aversion to noise. CONCLUSIONS: The questionnaire
      has proven to be a useful instrument to assess the quality of hearing in
      children. The possibility of bilateral implantation should be considered during
      the decision process prior to implantation.

PMID- 11967775
TI  - [Respiratory diseases and genotoxicity in tobacco smoke exposed children].
AB  - BACKGROUND: Tobacco smoke, containing more than 4800 chemical substances with a
      large number of mutagenic and carcinogenic compounds, is the most important
      indoor pollution. Aim of the study was to analyse the relationship between
      exposure of children (2-15 years) to environmental tobacco smoke (ETS) with the
      amount of respiratory diseases, the occurrence of atopic diseases and the risk
      for genotoxic damage. PATIENTS AND METHODS: Within the last 1.5 years 216
      children were included in the study. Smoking habits of the family, environmental
      settings, housing, nutrition, social and economic factors were assessed by a
      detailed questionnaire. Two different effect markers were used to assess
      molecular and genetic damage. Biochemical effect of ETS was quantified by 4
      aminobiphenyl-hemoglobin (4-ABP-Hb) adducts and the genotoxic damage was
      determined by chromosomal damage as seen in the micro nucleus test in
      lymphocytes. RESULTS: Chronic rhinosinusitis and allergic rhinitis are
      accumulated in the ETS-exposed children. In the ETS-group atopic diseases
      (allergic rhinitis, extrinsic asthma or neurodermatitis) were significantly more
      frequent (39.5 %, p = 0.01) than in the non-exposed group (23 %). In addition the
      genetic predisposition was significantly decreased in the ETS-group (20.8 %, p =
      0.048) compared to the non-exposed group (45 %). Until now, blood samples of 63
      individuals were analysed for Hb adducts and 92 for micro nuclei. Hemoglobin
      adducts of 4-ABP, a human carcinogenic aromatic amine, were significantly
      elevated in children with smoking parents (mean: 82.2pg/g Hb, p = 0.003) compared
      to children with non-smoking parents (mean: 60.6 pg/g Hb). ETS-exposed children
      showed significantly higher micro nucleus frequencies (mean ETS: 8.0/1000
      binucleate (BN) cells, p = 0.001) than non-ETS exposed children (mean: 6.2/1000
      BN cells). CONCLUSION: Our data underline the thesis, that ETS plays an important
      role for the development of atopic diseases. The significantly increased effect
      markers of tobacco smoke in exposed children give evidence, that ETS causes
      elevated molecular and genotoxic damage in children.

PMID- 11967776
TI  - [Skin prick test results in snoring and sleep apnea patients].
AB  - BACKGROUND: In allergic rhinitis, nasal obstruction is a typical symptom. Reduced
      nasal ventilation is thought to be one causal factor for sleep breathing
      disorders. Whether or not snoring individuals with or without sleep apnea show
      more frequent or stronger reactions in skin prick tests (SPT) compared to non
      snorers has not been investigated yet. METHOD: SPT on 20 most frequent allergens
      and standardized questionnaires of 412 patients of either sex who received a
      polysomnography at the sleeplab of the ENT department, University of Wurzburg,
      Germany, were analysed retrospectively. In 351 patients (85 %), data were
      complete. According to their polysomnography, patients were grouped into snorers
      (n = 248, 71 %) and non-snorers (n = 103, 29 %) or apnea (apnea-hypopnea-index >
      10; n = 171, 49 %) and non-apnea patients (n = 180, 51 %). Average occurrence or
      strength of skin reactions was compared between these groups. RESULTS: Except
      plantain (7 % vs. 1 %) and beech (10 % vs. 3 %), there were no statistical
      increases in the average occurrence or strength of SPT results in snoring
      individuals. Apnea patients did not show more frequent or stronger allergic skin
      reactions than non-apnea patients. Three patients suffering from allergic
      rhinitis by house dust mites were treated with citerizin 10 mg and allergen
      exposition prophylaxis. Three months after onset of therapy in all three
      patients, a reduction of snoring was polysomnographically observed. Snorers or
      apnea patients complaining sneezing, reduced nasal ventilation at night,
      hyperlacrimation or rhinorrhea showed significant higher numbers of allergic skin
      reactions for rye, gras and house dust mites compared to patients without these
      symptoms. CONCLUSIONS: The results reveal that only snorers or apnea patients
      with specific symptoms for allergic rhinitis should be tested by SPT. A general
      SPT-screening seems not to be indicated. Snoring and apneas in patients with
      allergic rhinitis due to house dust mites can be eliminated or reduced by an oral
      antihistaminic treatment.

PMID- 11967777
TI  - [Functional long-term results following hemipharyngo-hemilaryngectomy and
      microvascular reconstruction using the radial forearm flap].
AB  - BACKGROUND: The surgical treatment of advanced hypopharyngeal carcinomas with
      infiltration of the laryngeal skeleton often includes total laryngectomy for
      functional reasons, although tumor infiltration is limited to only one half of
      the larynx. When not only the infiltrated half of the thyroid cartilage but also
      the cricoid cartilage of the involved side has to be removed, in spite of
      adequate reconstruction using local or pedicled flaps (f. e. pectoralis major
      flap) persistent dysphagia and aspiration prevent oral food intake and closure of
      the tracheostoma. These functional disturbances are increased by the negative
      effects of postoperative radiotherapy, which has to be applied in most of the
      cases for oncological reasons. The routine use of free, microvascularly
      anastomosed flaps for reconstruction of defects following removal of extended
      carcinomas of the mouth, the tongue or the oropharynx as well as in total
      pharyngolaryngectomy led to considerable improvements in functional
      rehabilitation of swallowing and speech. An improved functional outcome is also
      reported following partial resections of the hypopharynx and reconstruction by
      means of these thin and pliable transplants (f. e. replacement of the entire
      posterior hypopharyngeal wall). METHOD: Since 1991 in 30 patients with a T3 or T4
      squamous cell carcinoma of the piriform sinus a complete hemipharyngo
      hemilaryngectomy including resection of the involved thyroid and cricoid
      cartilage was carried out. For reconstruction a radial forearm flap was dissected
      with two separate epithelial islands: The smaller island was used to create an
      epithelialized endolarynx, which allows complete closure of the glottis by the
      healthy vocal chord. With the bigger second island the hypopharynx was replaced,
      creating a highly mobile, adaptable neo-piriform-sinus, which was suspended to
      the ipsilateral half of the hyoid bone. Parts of the both islands were sutured
      together to create a new aryepiglottic fold. The laryngeal skeleton intentionally
      was not reconstructed. RESULTS: One year evaluation revealed 25 of the 30
      patients swallowing normal diet and being decannulated. 4 patients could take up
      a soft diet, 1 patient with a severe stricture at the entrance to the esophagus
      however had to be laryngectomized for functional reasons. Most of the patients
      judged their postoperative voice as satisfactory, although there was a different
      impairment of the voice (quite normal up to a marked hoarseness). During follow
      up (up to 10 years) 4 patients developed a local recurrence, in 3 cases a
      secondary metastasis after neck dissection occurred. In 3 patients a second
      primary was detected (oropharynx 2, esophagus 1), 3 patients died with lung
      metastases. CONCLUSION: Rehabilitation of normal swallowing and a satisfying
      voice restoration without a permanent tracheostoma following complete
      hemipharyngo-hemilaryngectomy can obviously be improved by the use of
      microvascular transplants (here radial forearm flap) in comparison to other
      surgical techniques. The necessary radical extirpation of these extended
      carcinomas also is guaranteed like in total laryngectomy, so that in spite of the
      advanced tumor stage an organ preserving surgery can be offered. A prolonged
      course of swallowing rehabilitation however has to be taken into consideration.

PMID- 11967778
TI  - [Cylindrocarcinoma in a patient with Brooke-Spiegler syndrome].
AB  - BACKGROUND: Cutaneous cylindromas are benign adnexal tumors that may occur as a
      solitary lesion or in a multiple familiar pattern. Malignant change is rare. The
      association of multiple trichoepitheliomas and cylindromas, the so called Brooke
      Spiegler Syndrome, is supposed to be inherited in an autosomal dominant manner.
      PATIENTS: A 55 year old woman presented with multiple skin tumors on the scalp,
      as well as the nasolabial and periauricular area since the age of 20 years. Her
      daughter and her nephew were also affected. Tumors were surgically removed for
      cosmetic reasons and showed histological signs of benign cylindromas and
      trichoepitheliomas. 35 years after diagnosis patient presented with a large
      exulceration on the right occipital area with intracranial invasion. Staging
      revealed multiple metastases in both lungs. Patient died 1 month later. RESULTS:
      Histological examination showed beside zones of massive necrosis multiple
      mitosis. The jigsaw puzzle pattern and the thick PAS positive basal layer, the
      striking characteristics of benign cylindromas, were lost. These histological
      findings and the clinical presentation led to the diagnosis of cylindrocarcinoma.
      CONCLUSIONS: Cylindrocarcinoma is an aggressive tumor with tendency to a local
      destructive growth and metastases. As malignant transformation of a benign
      cylindroma occurs more often in the multiple form a close follow-up of patients
      with multiple cylindromas is necessary. A family study is indicated.

PMID- 11967779
TI  - [Basic principles of in vivo regeneration in the area of the head and neck].

PMID- 11967780
TI  - [Stem cell biotechnology--revolution in established therapeutic methods?].

PMID- 11967781
TI  - [Growth factors in otorhinolaryngology].

PMID- 11967782
TI  - [Tissue engineering in otorhinolaryngology, head and neck surgery].

PMID- 11967783
TI  - The growing healthcare burden of CHF.
AB  - Despite advances in treatment, congestive heart failure (CHF) remains a major
      burden on healthcare budgets throughout the western world. Two main factors in
      the increasing incidence of CHF are the shift in the age distribution of the
      population and, paradoxically, an improvement in the management of other
      conditions, such as myocardial infarction. This increases the number of patients
      surviving acute cardiovascular events who proceed to develop CHF. Certain sub
      populations of patients consume most of the healthcare resources devoted to CHF
      management, with some 90% of resources utilised by patients in NYHA classes III
      or IV, and hospitalisation accounting for 60 to 75% of overall costs. Management
      strategies aimed at reducing both disease severity and the need for
      hospitalisation are therefore likely to be most effective in reducing the
      economic burden of CHF on healthcare systems.

PMID- 11967784
TI  - The past, present and future of hypertension management: a potential role for
      AT(1)-receptor antagonists.
AB  - The benefits of effective antihypertensive treatment were established at least 40
      years ago, but despite the availability of more reliable and better-tolerated
      antihypertensive drugs, the control of blood pressure remains poor in most
      patients. Long-term antihypertensive efficacy requires treatment that combines
      reliable 24-hour reduction of blood pressure with good tolerability to facilitate
      patient compliance. Treatment should also protect against target-organ damage. As
      the majority of negative cardiovascular effects of angiotensin II are mediated
      through the angiotensin II type 1 (AT(1)) receptor, specific blockade of this
      receptor is a rational approach for achieving these ideals. Several AT(1)
      receptor blockers have been developed that combine antihypertensive efficacy and
      placebo-like tolerability - the latter being unique in the history of
      antihypertensive therapy. In experimental animals these drugs prevent or reverse
      target organ damage in the heart, the vasculature and the kidney. Ongoing large
      scale outcome studies are now underway to establish the benefits of AT(1)
      receptor blockade beyond blood pressure control.

PMID- 11967785
TI  - Diagnosis of CHF--often a trap in itself.
AB  - The increasing clinical burden of congestive heart failure (CHF) is exacerbated
      by our limited abilities in clinically identifying the various aetiologies of the
      condition, such as the differentiation between systolic and diastolic heart
      failure. This denies appropriate therapy to a substantial proportion of patients,
      particularly outside specialised centres, and can even lead to the use of
      potentially deleterious interventions. The development of practically applicable
      definitions of the various types of CHF, combined with the rationalisation of
      diagnostic techniques, has helped both primary and secondary care physicians to
      target therapies appropriately to specific patient groups. This should reduce the
      number of misdiagnoses, thus minimising the proportion of patients 'falling
      through the net' of effective CHF management, and thereby improving clinical
      outcomes and the quality-of-life of those affected.

PMID- 11967786
TI  - Novel mechanisms linking angiotensin II and early atherogenesis.
AB  - We propose that Ang II exerts an as yet uncharacterized immunomodulatory effect
      on monocyte maturation, differentiation, or extravasation, which may depend on
      the myelomonocytic phenotype. Since the myelopoietic process originating at stem
      cells and culminating in release to the blood is at least 6 days, it is
      conceivable that the observation of reduced monocyte CD11b expression two weeks
      after completion of losartan treatment indicates a suppression of the CD11b
      phenotype in newly released CD14(+)/CD45(+) monocytes. Other studies employing
      suppression of AT(1)-receptors with deoxy-oligonucleotides have reported effects
      on blood pressure that surpass those predicted by the duration of the
      treatment.(87) These data would suggest that it is possible to interrupt a
      stimulatory signal by Ang II through a gene-related mechanism that in our
      experiments may reside in the mechanisms that regulate myelopoiesis. While our
      knowledge of the role of Ang II in the regulation of monocyte formation and
      function is incomplete, we have taken a first step in attempting to synthesize
      the data described above into a comprehensive hypothesis for further evaluation
      of the factors that initiate atherogenesis. Such effects may crucially contribute
      to the clinical benefit of AT(1)-receptor antagonists, independent of depressor
      effects, and may represent a paradigm for novel, anti-inflammatory actions by
      this class of drugs.

PMID- 11967787
TI  - Why we need new strategies in CHF management.
AB  - Despite recent improvements in drug therapy, the prevalence of congestive heart
      failure (CHF) continues to rise, as a result of the increasing proportion of
      older people in the population and factors such as greater survival rates after
      myocardial infarction. More effective management strategies for CHF are therefore
      needed urgently. The angiotensin II type 1 (AT(1))-receptor blockers might
      contribute to such strategies, offering placebo-like tolerability and showing
      promise in early trials of their use in CHF. Large-scale outcome studies,
      currently underway, will provide further evidence of the value of AT(1)-receptor
      blockers in CHF. In addition, the involvement of specially trained nurses in
      patient education and monitoring should enhance compliance with both existing and
      novel therapies, and thus help to increase the overall efficacy of holistic
      strategies for CHF management.

PMID- 11967788
TI  - The importance of early intervention in CHF--signs and symptom relief.
AB  - Effective treatments of congestive heart failure (CHF) must not only reduce
      mortality, but should also reduce the severity of the signs and symptoms of the
      syndrome, as these can have a major impact on quality of life. Early intervention
      can help to make everyday activities easier for patients with CHF and may slow
      disease progression. This review provides an overview of the efficacies of
      various therapies in improving the signs and symptoms of CHF, with particular
      reference to recent data from randomised, double-blind studies of patients
      receiving the AT(1)-receptor blocker, candesartan cilexetil.

PMID- 11967789
TI  - The HOPE Study (Heart Outcomes Prevention Evaluation).
AB  - The Heart Outcomes Prevention Evaluation (HOPE) study was designed to test the
      hypotheses that two preventive intervention strategies, namely angiotensin
      converting enzyme (ACE) inhibition or vitamin E, would improve morbidity and
      mortality in patients at high risk of cardiovascular events compared with
      placebo. This review addresses the ACE inhibitor (ACE-I) (ramipril) arm of the
      study, both on the trial population as a whole, and on the large diabetic
      subgroup. Patients were included in the study who were considered to be at high
      risk of future fatal or non-fatal cardiovascular events, by virtue of their age
      (>55 years), existing or previous cardiovascular disease, or diabetes. Diabetics
      had at least one other risk factor, either known vascular disease or other
      factors such as cigarette smoking, high cholesterol or hypertension. Ramipril or
      placebo was added to concomitant medication, which included, in a substantial
      proportion of patients, antihypertensive drugs (excluding ACE-I), lipid-lowering
      agents or aspirin. As a result, despite a history of hypertension in nearly 50%
      of patients, blood pressure (BP) at baseline was normal and the reduction in BP
      attributable to ramipril modest (a fall of 3-4 mmHg systolic BP and 1-2 mmHg
      diastolic). The trial was stopped early on the advice of the Data Monitoring
      Committee because of convincing evidence of the benefit of ramipril treatment on
      the combined primary endpoint of cardiovascular death, non-fatal myocardial
      infarct (MI) and non-fatal stroke (14% vs. 17.8% on ramipril and placebo,
      respectively; relative risk reduction 22%, p<0.001). This comprised a risk
      reduction of 32% for stroke, 20% for MI, 26% for cardiovascular death and 16% for
      all-cause mortality, as well as a reduction in the risk of several other
      endpoints including heart failure and revascularisation procedures. The results
      among the 3577 diabetic subjects were even more striking, with a reduction of 25%
      in the combined primary endpoint. This reduction in the combined endpoint and in
      particular the reduction in MI far exceeded that which would be expected from the
      modest fall in BP. Furthermore, a multiple regression analysis of the diabetic
      subgroup showed similar relative risk reductions even after allowing for the
      effects of the fall in BP. Possible explanations for the non BP-mediated benefits
      of ramipril include reduction of angiotensin II-induced intimal and vascular
      smooth muscle proliferation and possible plaque stabilisation. The HOPE study
      results show that it is both safe and beneficial to lower BP that is already
      within the 'normal' range, particularly in patients with known vascular risk
      factors. This should greatly extend the use of ACE-I to a wider group of patients
      - not only those with left ventricular dysfunction, hypertension or diabetic
      microalbuminuria, but to the sort of high-risk patients who are currently given
      prophylactic treatment with aspirin.

PMID- 11967790
TI  - Angiotensin II receptor blockers in chronic heart failure--not as ELITE as
      expected!
AB  - As with many large-scale long-term outcome trials, more questions have been posed
      than answered regarding the potential role of angiotensin II receptor blockers as
      first-line agents in chronic heart failure. Given the present data, in patients
      with left ventricular systolic dysfunction, ACE inhibitors must remain the
      treatment of choice, owing to the large body of data supporting their use in this
      clinical syndrome. However, ARBs seems a reasonable alternative for renin
      angiotensin axis blockade in the significant number of heart failure patients who
      are genuinely intolerant of ACE inhibitors. The pendulum has now swung back in
      favour of ACE inhibition for chronic heart failure, although one can only await
      with great expectation the results of the ongoing trials comparing not only
      angiotensin II receptor blockers with ACE inhibitors but a combination of the two
      with regards tolerability and survival. Whether this potentially useful class of
      drugs will ultimately become the cornerstone of heart failure therapy in place
      of, or in addition to, ACE inhibitors is still in debate, but hopefully we should
      not have to wait too long for the definitive answers.

PMID- 11967791
TI  - Role of chymase on vascular proliferation.
AB  - In the normal state, vascular ACE regulates local angiotensin II formation and
      plays a crucial role in the regulation of blood pressure, whereas chymase is
      stored in secretory granules in mast cells and has no enzymatic effects such as
      angiotensin II-forming activity. Chymase has a maximal activity immediately upon
      release into the extracellular matrix in vascular tissues after mast cells have
      been activated by a strong stimulus such as experienced by catheter-injured and
      grafted vessels. Therefore, chymase plays an important role in forming local
      angiotensin II when vascular tissues are injured, and inhibition of chymase may
      be useful for preventing vascular proliferation in grafted vessels and after PTCA
      (Figure 6).

PMID- 11967792
TI  - Neurohumoral blockade in CHF management.
AB  - Is heart failure an endocrine disease? Historically, congestive heart failure
      (CHF) has often been regarded as a mechanical and haemodynamic condition.
      However, there is now strong evidence that the activation of neuroendocrine
      systems, like the renin-angiotensin-aldosterone system (RAAS) and sympathetic
      nervous system, as well as the activation of natriuretic peptides, endothelin and
      vasopressin, play key roles in the progression of CHF. In this context, agents
      targeting neurohormones offer a highly rational approach to CHF management, with
      ACE inhibitors, aldosterone antagonists and beta-adrenergic blockade improving
      the prognosis for many patients. Although relevant improvements in clinical
      status and survival can be achieved with these drug classes, mortality rates for
      patients with CHF are still very high. Moreover, most patients do not receive
      these proven life-prolonging drugs, partially due to fear of adverse events, such
      as hypotension (with ACE inhibitors), gynaecomastia (with spironolactone) and
      fatigue (with beta-blockers). New agents that combine efficacy with better
      tolerability are therefore needed. The angiotensin II type 1 (AT(1))-receptor
      blockers have the potential to fulfil both these requirements, by blocking the
      deleterious cardiovascular and haemodynamic effects of angiotensin II while
      offering placebo-like tolerability. As shown with candesartan, AT(1)-receptor
      blockers also modulate the levels of other neurohormones, including aldosterone
      and atrial natriuretic peptide (ANP). Combined with its tight, long-lasting
      binding to AT(1)-receptors, this characteristic gives candesartan the potential
      for complete blockade of the RAAS-neurohormonal axis, along with the great
      potential to improve clinical outcomes.

PMID- 11967793
TI  - ACE inhibitors, angiotensin receptor antagonists and bradykinin.

PMID- 11967794
TI  - Blockade of the renin-angiotensin-aldosterone system and renal protection in
      diabetes mellitus.

PMID- 11967795
TI  - The safety and tolerability of candesartan cilexetil in CHF.
AB  - The management of congestive heart failure (CHF) continues to represent a major
      therapeutic challenge. The primary goal of any treatment is the improvement of
      symptoms with a reduction in CHF related morbidity and a neutral or beneficial
      effect on mortality. The number of hospitalisations is considered an important
      measure of morbidity and quality-of-life in these patients. This pooled safety
      analysis was performed on adverse event data from five placebo-controlled studies
      involving a total of 1893 patients, 1287 of whom received candesartan cilexetil
      and 606 of whom received placebo. These were the only placebo-controlled phase II
      and III studies of candesartan safety available at the time of the analysis, and
      investigated the efficacy and safety of candesartan cilexetil in patients with
      CHF. None was designed as an endpoint trial. A blinded, independent review of all
      adverse event data was performed to assess all-cause mortality and unexpected
      deaths, and hospitalisations for acute deterioration of CHF, chronic progression
      of CHF, other intercurrent events, or accidental injury/attempted suicide. The
      descriptive analysis included crude and cumulative incidence rates for mortality
      and cardiac and non-cardiac morbidity using the Kaplan-Meier method and the log
      rank test. The sample population was predominantly (approximately two thirds)
      male, with a median age of 61 years (range: 20-89 years). The median age for
      women in the sample population was 66 years (range: 26-86 years). Patients
      received candesartan cilexetil, 2-32 mg, over a median period of 84 days (range:
      1-418 days), or placebo over a median period of 85 days (range: 1-398 days). The
      results demonstrated a clinically non-significant trend for all relevant events
      (deaths and hospitalisations, whether related to CHF or not) to occur less
      frequently in patients receiving candesartan cilexetil than in patients receiving
      placebo (deaths - candesartan cilexetil: 1.6%, placebo: 1.8%; hospitalisations -
      candesartan cilexetil: 7.2%, placebo: 10.9%). There was a significant treatment
      difference in CHF hospitalisations (candesartan cilexetil: 3.0% vs. placebo:
      5.6%). The time to event analysis revealed that significantly fewer
      hospitalisations due to CHF occurred in the group receiving candesartan cilexetil
      than in the group receiving placebo. This treatment difference persisted
      throughout therapy (log-rank test; p < 0.028). These results show the safety of
      candesartan cilexetil, compared with placebo, in the treatment of patients with
      CHF.

PMID- 11967796
TI  - Mechanical strain-induced human vascular matrix synthesis: the role of
      angiotensin II.
AB  - INTRODUCTION: Reduced vascular compliance in patients with hypertension results
      from an increase in extra-cellular matrix (ECM) protein deposition in blood
      vessels. At least two key factors, namely mechanical strain and neurohumoral
      mediators, for example Angiotensin II (Ang II), promote fibrogenesis within
      vessel walls; however potential interactions between these have not been clearly
      defined. This work examined the direct effect of mechanical strain on matrix mRNA
      expression and protein synthesis by human vascular smooth muscle (VSM) cells and
      identified the importance of renin-angiotensin system (RAS) activation in stretch
      induced matrix production. METHODS: Human VSM cells were exposed either to a
      cyclical mechanical strain regimen or to Ang II in the presence or absence of the
      Ang II receptor (AT(1) R) antagonist losartan or its more potent metabolite
      EXP3174. Analysis of matrix mRNA expression (Northerns) and protein synthesis
      (ELISA) and cellular AT(1)-receptor protein expression (Westerns) were
      determined. RESULTS: Ang II increased both collagen alpha1 (92%, SEM +/- 20%)
      mRNA expression and fibronectin (21% +/- 6%) protein synthesis in static VSM
      cells compared with unstimulated controls. The effect of Ang II was attenuated by
      antagonism of the AT(1)-receptor (AT(1) R). Similarly, mechanical strain induced
      an increase in both collagen alpha1 (102% +/- 30%) mRNA expression and
      fibronectin (50% +/-21%) protein synthesis. Surprisingly, in the absence of
      exogenous Ang II, AT(1)-receptor blockade attenuated this stretch-induced
      increase in matrix synthesis. Mechanical strain also induced an increase in total
      cellular AT(1)-receptor protein (30.7% +/- 3.5%) compared with static cells.
      CONCLUSION: Both mechanical strain and Ang II increased matrix gene expression
      and protein synthesis by human VSM cells. The effect of strain was attenuated by
      AT(1)-receptor antagonism. Our results further suggest that mechanical strain may
      sensitise human VSM cells to the fibrogenic actions of Ang II, perhaps via
      upregulation of the AT(1)-receptor.

PMID- 11967797
TI  - Rat model for investigating ACTH-independent angiotensin-induced aldosterone
      secretion.
AB  - Study of the acute effects of angiotensin II (Ang II) on aldosterone secretion
      has been hindered by the confounding influence of Ang II-induced
      adrenocorticotropic hormone (ACTH) secretion on aldosterone secretion, and by the
      fact that when laboratory rats are fed standard laboratory chows that are high in
      sodium, the adrenal is only minimally responsive to Ang II. In this study, we
      report the development of a model of Ang II-induced aldosterone secretion in NaCl
      deprived, dexamethasone (DEX)-treated rats. This model allows the observation of
      (a) a high magnitude of Ang II-induced aldosterone secretion, (b) a return of
      plasma aldosterone levels to baseline after stimulation, and (c) aldosterone
      secretion without the potentially confounding influence of ACTH stimulation.

PMID- 11967798
TI  - Reduction of resistance artery stiffness by treatment with the AT(1)-receptor
      antagonist losartan in essential hypertension.
AB  - In spontaneously hypertensive rats resistance artery structure, endothelial
      dysfunction and geometry-independent wall stiffness were reduced by an
      angiotensin AT(1)-receptor antagonist. In previous studies of human hypertension,
      interruption of the renin-angiotensin system corrected small artery structure and
      endothelial dysfunction, whereas the beta-blocker atenolol did not. We
      hypothesized that the AT(1)R antagonist losartan, but not the beta-blocker
      atenolol, would reduce stiffness of gluteal subcutaneous small arteries in
      essential hypertensive patients. Seventeen untreated mild essential hypertensive
      patients (47+/-2 years; 75% male) were randomly assigned in double-blind fashion
      to losartan or atenolol treatment for one year. Small, resistance size arteries
      were studied on pressurized myographs. Blood pressure (mmHg) was reduced (p<0.01)
      from 145 +/- 4/101 +/- 2 and 147 +/- 6/98 +/- 2 to 128 +/- 4/86 +/- 2 and 131 +/-
      3/84 +/- 1 by losartan and atenolol, respectively. The media/lumen ratio of small
      arteries was unaffected by atenolol (8.3+/-0.3% before and 8.8+/-0.5% after
      treatment). In contrast, losartan reduced media/lumen ratio from 8.4+/-0.4% to
      6.7+/-0.3% (p<0.01). Whereas isobaric elastic modulus was unaffected by either
      treatment, geometry-independent stiffness (slope of elastic modulus vs. stress)
      was reduced from 9.7+/-1.2 to 6.1+/-0.9 (P<0.05) under losartan treatment, but
      was unchanged by atenolol (8.2+/-1.3 to 7.8+/-0.6). In conclusion, treatment with
      losartan reduced stiffness and structural alterations of subcutaneous resistance
      arteries of previously untreated essential hypertensive patients, whereas
      atenolol failed to do so.

PMID- 11967799
TI  - Losartan-induced apoptosis as a novel mechanism for the prevention of vascular
      lesion formation after injury.
AB  - Smooth muscle cell (SMC) apoptosis is transiently increased at the onset of the
      regression of aortic hypertrophy in spontaneously hypertensive rats (SHR) treated
      with the angiotensin II AT(1) antagonist losartan. We postulated that losartan
      induction of SMC apoptosis contributes to suppression of neointimal hyperplasia
      after vascular injury. Losartan or placebo treatment was initiated two days
      before balloon injury in the SHR aorta. Compared with time-matched placebo,
      losartan decreased neointimal cross-sectional area at Days 5 and 10 after injury
      by 50% and 64% respectively, without affecting medial mass. At Day 10, losartan
      significantly decreased SMC number (by 56%) in the neointima, but not in the
      media. DNA synthesis was significantly inhibited at Day 5 but not at Day 10.
      Losartan significantly increased aortic DNA fragmentation by 2.6- and 4.1-fold,
      at Days 5 and 10, respectively. In situ labeling of SMC with terminal
      deoxynucleotidyltransferase revealed significant 61% and 68% increases in
      apoptotic SMC at Days 5 and 10 with losartan treatment, predominantly in the
      neointima. Thus, losartan suppressed neointima formation in part by the induction
      of SMC apoptosis, which may be dissociated from the inhibition of DNA synthesis.
      Therefore, losartan-induced SMC apoptosis may be a potential therapeutic approach
      to control occlusive vascular disorders.

PMID- 11967800
TI  - ACE inhibitors in hypertension: still a shortage of evidence.

PMID- 11967801
TI  - ACE inhibition and the kidney: species variation in the mechanisms responsible
      for the renal haemodynamic response.

PMID- 11967802
TI  - AT(1)-signalling in vascular smooth muscle.
AB  - Angiotensin II activates multiple signalling pathways in vascular smooth muscle.
      The precise pattern of signals and their relative importance to a particular
      functional response depends on both cell type and differentiation state. Although
      the contractile and trophic effects of Ang II are often thought of as distinct
      responses it is increasingly difficult to differentiate them in terms of
      signalling pathways. Since vasoconstriction and abnormal growth are both features
      of circulatory diseases such as hypertension and atherosclerosis a better
      understanding of the signalling pathways responsible for the vasoconstrictor and
      trophic actions of this peptide may help define novel therapeutic targets in
      cardiovascular disease.

PMID- 11967803
TI  - Ongoing Clinical trials with angiotensin II receptor antagonists in chronic heart
      failure and myocardial infarction.

PMID- 11967805
TI  - The renin angiotensin system and cardiovascular disease: hope or hype?

PMID- 11967804
TI  - Insights derived from ACE knockout mice.
AB  - The evaluation of ACE knockout mice has illustrated the tremendous physiologic
      importance of the RAAS. We have discussed how interruption of this system
      influences blood pressure, renal function, renal development, serum and urine
      electrolyte composition, haematocrit and male reproductive capacity. This body of
      data underlines the modelling of the RAAS as a type of biological machine that is
      positioned to respond to environmental insult and to maintain a homeostasis of
      blood pressure, blood volume and electrolyte composition. These data also
      emphasise Harry Goldblatt's seminal observation that the kidney and the RAAS are
      intimately linked in the regulation of normal blood pressure.

PMID- 11967806
TI  - Persistent formation of angiotensin II despite treatment with maximally
      recommended doses of angiotensin converting enzyme inhibitors in patients with
      chronic heart failure.

PMID- 11967807
TI  - Combination of non-hypotensive doses of valsartan and enalapril improves survival
      of spontaneously hypertensive rats with endothelial dysfunction.
AB  - There is increasing evidence to suggest endothelial dysfunction as a critical
      factor in vascular diseases. Genetically predisposed spontaneously hypertensive
      rats (SHR) treated with inhibitors of nitric oxide (NO) synthase, develop a
      severe hypertensive nephrosclerosis without the necessity for surgical reduction
      in renal mass, nephrectomy, renal infarction or nephrotoxic drugs. In these
      animals, endothelial dysfunction is considered a valid model for assessment of
      the efficacy of cardiovascular therapy. SHR were treated with either the
      angiotensin-converting enzyme inhibitor enalapril or the angiotensin II (Ang II)
      AT(1)-receptor antagonist (AIIA) valsartan at sub-hypotensive doses and the
      effects on survival rates, cardiac and renal changes were monitored. Rats treated
      with valsartan, alone or in combination with enalapril, showed markedly higher
      survival rates (67-85%, respectively) than untreated animals (37%) or those
      treated with enalapril alone (55%). Valsartan at a dose which attenuated blood
      pressure increase led to even greater survival rates (95%). Despite these
      improved survival rates, at non-hypotensive doses the drugs had no effect on
      histological appearance, nor was kidney function improved. Plasma creatinine
      levels were reduced by valsartan, alone or in combination with enalapril, but
      proteinuria persisted with all treatments over the 12 weeks of the study.
      Aldosterone levels were significantly reduced by all treatments. The results
      suggest a beneficial role for endothelium in hypertension. Reduced renal
      perfusion pressure probably underlies the beneficial renal effects of high-dose
      valsartan.

PMID- 11967808
TI  - Binding characteristics of [(3)H]-irbesartan to human recombinant angiotensin
      type 1 receptors.
AB  - The aim of the present work was to investigate the binding properties of the
      selective AT(1)-receptor antagonist irbesartan to human AT(1)-receptors by direct
      radioligand binding. For this purpose the specific binding of [(3)H]-irbesartan
      to intact Chinese Hamster Ovary (CHO) cells expressing human recombinant AT(1)
      receptors was determined. Specific binding of [(3)H]-irbesartan rapidly reached
      equilibrium and was saturable with a KD of 1.94 +/- 0.12 to a homogeneous class
      of binding sites. Its binding was inhibited by other AT(1) antagonists (AIIAs)
      with the same potency order as previous results from [(3)H]-angiotensin II and
      [(3)H]-candesartan binding to human AT(1)-receptors. Whereas the dissociation
      rate of [(3)H]-irbesartan was essentially independent of the radioligand
      concentration, it was much slower at 12 degrees C when compared with 37 degrees
      C. Moreover, the dissociation rate was similar, as determined in washout
      experiments in the absence or presence of unlabelled AT(1) antagonists. At 37
      degrees C the dissociation rate constant corresponded to a half-life of
      approximately seven minutes, which is sufficient to explain the partially
      insurmountable inhibition by irbesartan in previous studies. In contrast, other
      phenomena such as the plasma half life and tissue-related factors are necessary
      to explain its sustained in vivo antihypertensive effect.

PMID- 11967809
TI  - Molecular mechanism(s) of insulin action on the expression of the angiotensinogen
      gene in kidney proximal tubular cells.
AB  - To investigate the molecular mechanism(s) of insulin action on the expression of
      the angiotensinogen (ANG) gene in kidney proximal tubular cells, we constructed a
      fusion gene, pOGH (hANG N-1064/+27), containing the 5'-flanking regulatory
      sequence of the human ANG gene fused with the human growth hormone (hGH) gene as
      a reporter and stably integrated the fusion gene into the opossum kidney (OK)
      cell genomes. The level of expression of pOGH (hANG N-1064/+27) was quantified by
      the amount of immunoreactive hGH secreted into the medium. The addition of a high
      level of D(+)-glucose (25 mM) or phorbol 12-myristate 13-acetate (PMA, 10(-7) M)
      stimulated the expression of the fusion gene in OK cells. The stimulatory effect
      of glucose (25 mM) was blocked by insulin and tolrestat (an inhibitor of aldose
      reductase). Tolrestat also inhibited the increase of cellular DAG and PKC
      activity stimulated by 25 mM glucose. While insulin did not affect the cellular
      DAG and PKC activity, it did block the stimulatory effect of high glucose (25 mM)
      and PMA on the expression of the fusion gene. Finally, PD98059 (an inhibitor of
      mitogen-activated protein kinase kinase (MEK)) enhanced the stimulatory effect of
      high levels of glucose and blocked the inhibitory effect of insulin on the
      expression of the fusion gene as well as on the phosphorylation of MEK and
      mitogen-activated protein kinase (MAPK). In contrast, Wortmannin (an inhibitor of
      phosphatidylinositol-3-kinase) did not block the inhibitory effect of insulin on
      the ANG gene expression. These studies demonstrate that the action of insulin,
      blocking the stimulatory effect of a high level of D(+)-glucose (25 mM) on the
      ANG gene expression is mediated, at least in part, via the 5'-flanking region of
      the ANG gene and MAPK signal transduction pathway.

PMID- 11967810
TI  - Losartan inhibits in vitro platelet activation: comparison with candesartan and
      valsartan.
AB  - A recent study has shown that losartan, an AT(1)-receptor antagonist, interacts
      with thromboxane A(2) (TxA(2))/prostaglandin H(2) (PGH(2)) receptors in human
      platelets. The aim of the present study was to analyse the ability of different
      angiotensin II (Ang II) AT(1)-receptor antagonists to inhibit TxA(2)-dependent
      human platelet activation. Platelets were obtained from healthy volunteers and
      were stimulated with the thromboxane A(2) analogue, U46619 (10(-6) mol/L). U46619
      stimulated platelet activation was significantly reduced by losartan in a dose
      dependent manner. Only maximal doses of valsartan (5x10(-6) mol/L), reduced
      U46619-induced platelet activation. The active form of candesartan cilexetil,
      candesartan (CV-11974), failed to modify platelet activation. Losartan reduced
      the binding of [(3)H]-U46619 to platelets, an effect that was observed to a
      lesser extent with valsartan but not with CV-11974. These results suggest that,
      whilst some AT(1)-receptor antagonists reduce TxA(2)-dependent human platelet
      activation, it is not a feature common to all AT(1) antagonists.

PMID- 11967811
TI  - Nitric oxide mediates inhibitory effect of losartan on angiotensin-induced
      contractions in hamster but not rat aorta.
AB  - We investigated a possible contribution of nitric oxide (NO) and prostaglandins
      to the inhibitory effect of losartan on contractions to Ang I (10(-6) M) and Ang
      II (10(-7) M) with or without L-NAME (10(-4) M) or indomethacin (10(-5) M) in the
      aorta of WKY, SHR and hamster (n=7 each). Rings of thoracic aorta (2-mm long)
      were placed in a myograph (5 ml). Endothelium-dependent vasodilations were
      evaluated with acetylcholine (10(-8) to 10(-6) M). After a 45-minute incubation
      with L-NAME under a resting tension of 2 g, only hamster aorta contracted
      (p<0.01). The SHR aorta showed impaired relaxations to acetylcholine compared
      with the WKY and hamster aorta (p<0.05). Despite the difference in the stimulated
      NO release, losartan completely abolished the responses to Ang I and Ang II both
      in WKY and SHR vessels irrespective of the presence of L-NAME. In contrast to the
      rat aorta, the inhibitory effect of losartan was attenuated in the presence of L
      NAME in the hamster aorta (78% vs 99% inhibition, p<0.05). Indomethacin did not
      alter the effect of losartan in any vessels. Our results suggest that the
      presence of NO, particularly a basal secretion of NO, is necessary for the full
      expression of the inhibitory effect of losartan in the hamster, but not in WKY or
      SHR, aorta. Unlike NO, prostaglandins do not appear to play a role in the effect
      of losartan.

PMID- 11967812
TI  - Cardioprotection after angiotensin II type 1 blockade involves angiotensin II
      type 2 receptor expression and activation of protein kinase C-epsilon in acutely
      reperfused myocardial infarction in the dog. Effect of UP269-6 and losartan on
      AT1 and AT2-receptor expression and IP3 receptor and PKCepsilon proteins.
AB  - To determine whether cardioprotection after chronic angiotensin II (Ang II) type
      1 (AT(1)) receptor blockade involves Ang II type 2 (AT(2)) receptor expression
      and protein kinase C-epsilon (PKC(epsilon)) activation, we measured in vivo
      haemodynamics and left ventricular (LV) remodelling and dysfunction
      (echocardiogram/ Doppler) and ex vivo AT(1)/AT(2)-receptor expression, IP(3)R (1,
      4, 5-inositol trisphosphate type 2 receptor) and PKC(epsilon) proteins in dogs
      with acutely reperfused (90 minutes ischaemia, 90 minutes reperfusion) myocardial
      infarction (MI) following seven days of AT(1)-receptor blockade with oral
      losartan or UP269-6. The animals were randomised to sham; sham + losartan or
      UP269-6; MI alone; MI + losartan; MI + UP269-6. More marked AT(1)-receptor
      blockade with UP269-6 (greater inhibition of Ang II pressor responses) was
      associated with a smaller increase in preload, less systolic and diastolic
      dysfunction, less infarct expansion, and smaller LV diastolic and systolic
      volumes. However, both AT(1)-receptor antagonists decreased infarct size.
      Importantly, MI decreased AT(1)-receptor and AT(2)-receptor expression while MI
      after AT(1)-receptor antagonism increased AT(1)-receptor (mRNA, not protein) and
      AT(2)-receptor (mRNA and protein) expression as well as IP(3)R and PKC(epsilon)
      proteins and cyclic guanosine 3', 5' monophosphate (cGMP). These results suggest
      that cardioprotection induced by chronic AT(1)-receptor antagonism involves
      enhanced AT(2)-receptor expression and possibly downstream signalling through
      IP(3)R, PKC(epsilon) and cGMP.

PMID- 11967813
TI  - Angiotensin II does not mediate the pressor response to PGD2 (icv).
AB  - The objective of the present studies was to examine the interaction between brain
      derived angiotensin II (Ang II) and prostaglandins in order to identify the
      mechanisms mediating the pressor response produced by these neuroregulators.
      Inhibiting synthesis of prostaglandins with indomethacin [indocin, 200 microg/ 5
      microl artificial cerebrospinal fluid (aCSF)], administered
      intracerebroventricularly (icv) to conscious adult male Sprague-Dawley rats,
      reduced blood pressure to values below basal levels. When injected prior to Ang
      II (50 ng/5 microl aCSF; icv), indomethacin completely abolished the pressor
      response induced by the octapeptide. The increase in blood pressure produced by
      prostaglandin D(2) (PGD(2), 20 microg/5 microl; icv), the most prominent
      prostaglandin in the rat brain, however, was not prevented by losartan (25
      microg/5 microl; icv), an Ang II AT(1)-receptor antagonist. Collectively, these
      results indicate that prostaglandins produced tonically in the brain maintain
      resting arterial blood pressure and that the pressor action of Ang II is
      dependent on de novo synthesis of a prostaglandin.

PMID- 11967814
TI  - Losartan reduces sympathetic nerve outflow from the brain of rats with chronic
      renal failure.
AB  - Sympathetic nervous system (SNS) activity, measured by norepinephrine (NE)
      turnover rate, was greater in the posterior hypothalamic (PH) nuclei, the
      paraventricular nuclei (PVN), and the locus coeruleus (LC) of 5/6 nephrectomised
      (CRF) rats than of control rats. NE secretion from the PH was also greater in CRF
      than in control rats. These findings demonstrate that SNS activity plays an
      important role in the genesis of hypertension associated with CRF. The increase
      in central SNS activity was mitigated by increased local expression of nitric
      oxide synthase (NOS)-mRNA and nitric oxide (NOx) production. Because angiotensin
      II may stimulate the central SNS, we tested the hypothesis that losartan, a
      specific angiotensin II AT(1)-receptor antagonist, may lower blood pressure (BP),
      at least in part, by central noradrenergic inhibition. To this end, we studied
      two groups of CRF rats. One group received losartan (10 mg/kg body weight) in
      drinking water between the 3rd and 4th week after nephrectomy, the second group
      received drinking water without losartan. SNS activity was measured by NE
      secretion from the PH using the microdialysis technique. NOS-mRNA gene expression
      was also measured by RT-PCR in the PH, PVN, and LC of CRF and control rats.
      Losartan reduced systolic BP from 184+/-3.7 to 152+/-3.1 mmHg and NE secretion
      from the PH from 340+/-9.7 to 247+/-4.8 pg/ml. CRF rats treated with losartan
      manifested a significant (p<0.01) increase in the expression of nNOS-mRNA in the
      PH (from 84+/-1.2 to 99+/-2.6), the PVN (from 44+/-1.5 to 63+/-2.1), and the LC
      (from 59+/-6.7 to 76+/-2.1). CRF rats also manifested a significant increase
      (p<0.01) in the expression of IL-1beta the PH (from 41.6+/-2.8 to 54.3+/-1.4),
      PVN (from 44+/-1.9 to 54+/-1.5), and LC (from 35.5+/-1.6 to 53.5+/-1.9). In
      conclusion, these studies suggest that the antihypertensive action of losartan in
      CRF rats may be mediated, at least in part, by inhibition of central SNS outflow.
      The studies also suggest that the inhibitory action of losartan on the SNS may be
      mediated by activation of IL-1beta, which, in turn, stimulates nNOS, an important
      modulator of central SNS activity.

PMID- 11967815
TI  - Recruitable ACE and tissue repair in the infarcted heart.
AB  - Constitutive angiotensin-converting enzyme (ACE) is bound to endothelial cells
      where it serves to regulate circulating concentrations of angiotensin II (Ang II)
      that normally contribute to circulatory homeostasis. Recruitable ACE, bound to
      macrophage and myofibroblast cell membrane, regulates local concentrations of Ang
      II involved in tissue repair. De novo generation of Ang II modulates expression
      of TGF-beta1 whose autocrine/paracrine properties regulate collagen turnover at
      sites of fibrous tissue formation that appear in response to various forms of
      injury in diverse tissues. Persistent myofibroblasts and their ACE activity at
      the infarct site contribute to a sustained metabolic activity that can account
      for a progressive fibrosis at, and remote to, sites of myocardial infarction.
      Activation of the circulating renin-angiotensin-aldosterone system with sustained
      elevations in plasma Ang II and aldosterone induce a pro-inflammatory vascular
      phenotype of small arteries and arterioles. This further promotes the appearance
      of recruitable ACE bound to macrophages and myofibroblasts involved in vascular
      remodelling. Locally produced Ang II from these vascular sites leads to
      perivascular fibrosis of intramural coronary vasculature of non-infarcted
      myocardium. At these sites, remote to the infarct, such adverse structural
      remodelling by fibrous tissue eventuates in ICM, a major aetiologic factor
      involved in the appearance of chronic cardiac failure and contributes to its
      progressive nature.

PMID- 11967816
TI  - Practical implications of current natriuretic peptide research.
AB  - Since the original discovery of atrial natriuretic peptide (ANP) nearly 20 years
      ago and the subsequent realisation of the existence of a family of natriuretic
      peptides, there has been considerable progress in the elucidation of the
      physiological and pathophysiological significance of these peptides. This review
      has examined two potentially important practical aspects arising from natriuretic
      peptide research - the significance of measurement of plasma levels of ANP and of
      brain natriuretic peptide BNP for cardiovascular disease and the therapeutic
      potential of targeting the natriuretic peptide system. Several situations where
      the measurement of plasma ANP and BNP may be of benefit in the overall assessment
      and prognosis of cardiac disease have been discussed. The measurement of plasma
      levels of these peptides appears to have limited value as a specific diagnostic
      tool and is unlikely to replace well-established procedures to assess cardiac
      function. Nevertheless, given the strong negative predictive value, the value of
      the measurement of plasma natriuretic peptides particularly BNPs, in people with
      suspected heart disease, rests on the evidence that a normal value indicates a
      low risk of cardiac impairment. Moreover, a consistently elevated plasma level of
      BNP after myocardial infarction is associated with a distinctly poor prognosis.
      In turn, this may help to select those with high plasma levels for subsequent
      detailed investigation of cardiac dysfunction. This may be an important option,
      especially where the facilities for the more invasive cardiological procedures
      are not available. Intriguingly, recent research also suggests the possibility
      that plasma levels of natriuretic peptides may have an important role in guiding
      more effective therapy for heart failure. The potent cardiovascular and renal
      effects of ANP and BNP provide an important therapeutic potential for
      hypertension and for conditions associated with volume overload. A number of
      approaches which have been used to enhance endogenous activity of these peptides
      have been highlighted. The use of the native peptides ANP and BNP may well be
      valuable in some circumstances, such as in critically ill individuals with
      congestive heart failure or renal failure. However, the limitations of the use of
      peptides, especially for long-term treatment, are obvious. In view of this,
      considerable effort has been devoted to the development of orally active agents
      to enhance endogenous natriuretic peptides by inhibition of breakdown by neutral
      endopeptidase. This research has led to the development of vasopeptidase
      inhibitors - dual inhibitors of both endopeptidase and angiotensin-converting
      enzyme - to enhance endogenous natriuretic peptide function on a background of
      reduced angiotensin II activity. The broad spectrum of action and the potentially
      important target-organ protection of these inhibitors offer potential benefits
      which may well go beyond existing treatment of hypertension and of conditions
      associated with overt volume overload.

PMID- 11967817
TI  - Genetic basis of cardiovascular disease--the renin-angiotensin-aldosterone system
      as a paradigm.

PMID- 11967818
TI  - To block the renin system or the calcium channel in hypertension--where do we
      stand?

PMID- 11967819
TI  - The losartan renal protection study--rationale, study design and baseline
      characteristics of RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin
      II Antagonist Losartan).
AB  - The RENAAL Study is a double-blind, placebo-controlled trial to evaluate the
      renal protective effects of losartan in Type 2 diabetic patients with
      nephropathy. The study has enrolled 1513 patients and is expected to continue for
      3.5 years after the last patient has been entered. Eligible patients must have a
      urinary albumin:creatinine ratio of at least 300 mg/g and serum creatinine
      between 1.3 to 3.0 mg/dL. Eligible hypertensive or normotensive patients are
      randomised to receive either losartan or placebo, in addition to their existing
      antihypertensive therapy. Medications that block angiotensin production or
      action, are excluded. The primary endpoint is a composite of the time to first
      event of doubling of serum creatinine, end-stage renal disease, or death;
      secondary endpoints include cardiovascular events, progression of renal disease,
      and changes in proteinuria; tertiary endpoints include quality of life,
      healthcare resource utilisation, and amputations. Patients include Caucasians
      (48.6%), Blacks (15.2%), Asians (16.7%), and Hispanics (18.2%). Baseline urinary
      albumin:creatinine ratio and serum creatinine levels average 1867 mg/g and 1.9
      mg/dL, respectively. Mean systolic and diastolic blood pressures are 153 and 82
      mmHg, respectively. RENAAL will document whether blockade of the AII receptor
      with losartan produces clinical benefits in patients with Type 2 diabetes and
      nephropathy.

PMID- 11967821
TI  - Transforming growth factor-beta(1) induces angiotensin-converting enzyme
      synthesis in rat cardiac fibroblasts during their differentiation to
      myofibroblasts.
AB  - OBJECTIVES: Appearance of angiotensin-converting enzyme (ACE) in fibrotic tissue
      can be the result of the action either of one particular growth factor or of
      cross-talk between multiple factors. Transforming growth factor-beta1 (TGF
      beta(1)) is an effective inducor of the differentiation of cultured fibroblasts
      to myofibroblasts, which are heterogeneous cells with different phenotypes. The
      present study investigated whether TGF-beta(1) is able to induce, in vitro, the
      differentiation of cultured fibroblasts to myofibroblasts with a phenotype
      containing ACE. DESIGN: Adult rat cardiac ventricular fibroblasts were obtained
      from hearts perfused with collagenase. Cells from second passage were always
      used. Rat cardiac ventricular fibroblasts were incubated with TGF-beta(1) (10
      ng/ml) for seven days. Cell characterisation was performed using light microscopy
      and indirect immunostaining. Presence of vimentin, desmin, factor VIII, alpha
      smooth muscle actin, and ACE was checked with both immunostaining and Western
      blotting. ACE activity was measured fluorometrically with hippuryl-histidyl
      leucine as substrate. Synthesis of DNA was measured as (3)H-thymidine
      incorporation. RESULTS: Fibroblasts contained two types of activity of hip-his
      leu degradation, namely a lisinopril-dependent activity (ACE activity) and a
      lisinopril-independent activity ('ACE-like' activity) which is performed by
      peptidase(s) other than ACE. The ACE activity constituted approximately 30% of
      the total activity. TGF-beta(1) induced an increase in both ACE activity and ACE
      protein (detected by immunoblotting) by 4.5 +/- 0.9- and 6.9 +/- 2.0-fold,
      respectively (p<0.05). This induction of ACE was accompanied by a profound
      modification of the fibroblasts phenotype, which consisted of a change in cell
      morphology, an enlargement of cell volume and an increase in cell protein
      content. TGF-beta(1) profoundly inhibited (3)H-thymidine incorporation and the
      number of cells in growing cultures. The induction of alpha-smooth muscle actin
      by TGF-beta(1) (6.8 +/- 2.8-fold increase, p<0.05) simultaneously with these
      modifications in cell morphology and proliferation indicates the appearance of
      myofibroblasts. These myofibroblasts did not contain desmin. CONCLUSION: TGF
      beta(1) is able to induce the appearance of ACE in cultures of adult rat cardiac
      ventricular fibroblasts. The appearance of the enzyme is accompanied by the
      differentiation of fibroblasts to myofibroblasts.

PMID- 11967820
TI  - The pharmacological potency of various AT(1) antagonists assessed by Schild
      regression technique in man.
AB  - RATIONALE: A quantitative technique was used to compare the pharmacological
      potency in healthy volunteers of angiotensin II receptor antagonists (AIIA):
      candesartan cilexetil, losartan, irbesartan, valsartan, and telmisartan. METHODS:
      In a randomised, double-blind, parallel-group (4x12 subjects) study, single oral
      doses of candesartan cilexetil 4, 8 and 16 mg, losartan potassium 25, 50 and 100
      mg, valsartan 40, 80 and 160 mg, and irbesartan 75, 150 and 300 mg were
      administered on three consecutive days. Telmisartan 20, 40 and 80 mg was
      similarly evaluated in 12 volunteers in an open amendment. Angiotensin II (Ang
      II) antagonistic effects were determined in vivo from rightward shifts in Ang II
      dose-response curves for diastolic blood pressure (BP) and dose ratios were
      calculated. Apparent K(i)-doses, i.e. doses (in mg) required to induce a two-fold
      shift in Ang II dose-response curves (equivalent to approx. 50% blockade of
      receptors) were determined, using Schild regression analysis. RESULTS: All
      treatments dose-dependently attenuated increases in diastolic BP induced by
      infusion of exogenous Ang II. Candesartan cilexetil appeared to have a more
      pronounced increase in effect following cumulative dosing. At 24 hours, apparent
      K(i)-doses were: candesartan cilexetil 6 mg, irbesartan 123 mg, valsartan 93.5
      mg, and telmisartan 54 mg. It was not possible to determine an apparent K(i)-dose
      for losartan at 24 hours. CONCLUSION: Consistent with results from experimental
      pharmacology, candesartan cilexetil displayed the highest pharmacological potency
      (i.e. antagonistic activity per mg substance) of the AIIAs tested. Apparent K(i)
      doses at 24 hours were within the dose range recommended for clinical use in
      patients with hypertension.

PMID- 11967822
TI  - The renin-angiotensin-aldosterone system is suppressed in adults with Type 1
      diabetes.
AB  - Poor glycaemic control and high blood pressure are two important risk factors for
      the development of retinopathy and nephropathy in Type 1 diabetes. The renin
      angiotensin-aldosterone system (RAAS) may be involved in this process, since
      treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the
      development of these complications. We investigated whether plasma renin activity
      (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP)
      differed in Type 1 diabetic patients compared with healthy controls. We recruited
      80 patients with Type 1 diabetes of more than 10 years' duration and 75 age
      matched controls. We found that PRA and Ang II concentrations were significantly
      lower in patients than in the controls. The levels of ANP, on the other hand,
      were higher in patients than in controls. PRA correlated negatively to the mean
      value of HbA(1c) during the previous five years. PRA and Ang II were
      significantly lower in patients with mean HbA(1c) >8.4% compared with those with
      mean HbA(1c) <7.2%. In summary, we found patients with Type 1 diabetes to have
      RAAS suppression and increased ANP levels, suggesting a state of fluid retention.

PMID- 11967823
TI  - Effects of the mineralocorticoid fludrocortisone on fibrinolytic function in
      healthy subjects.
AB  - Recent evidence suggests that the renin-angiotensin-aldosterone system (RAAS) may
      participate in the regulation of fibrinolytic function. Angiotensin II (Ang II)
      is the primary candidate to mediate this inter-relationship, since this peptide
      is capable of stimulating plasminogen activator inhibitor-1 (PAI-1) in vitro and
      in vivo. It has been suggested that aldosterone may also modulate fibrinolysis,
      possibly by interacting with Ang II. The present study therefore investigates the
      effect of short-term treatment with the synthetic mineralocorticoid
      fludrocortisone (F) on fibrinolytic function. Ten healthy male volunteers, aged
      25 to 30 years, on a constant intake of 160-180 mmol Na(+) and 60-80 mmol K(+),
      were studied on a control day (C1), after two days of oral administration of F
      (0.1 mg b.d.), and again three days after cessation of F (C2). F was associated
      with a marked decrease in plasma renin activity (PRA) from 0.91 +/- 0.45 ng ml(
      1) h(-1) to 0.34 +/- 0.29 ng ml(-1) h(-1) (p=0.005), which returned to the
      baseline range at C2 (0.65 +/- 0.45 ng ml(-1) h(-1); p=0.032). The experimental
      protocol was not associated with significant changes in the activity or antigen
      concentration of tissue plasminogen activator (t-PA). PAI-1 exhibited a circadian
      rhythm with highest values at 0800 hours (41.8 +/- 9.1 ng/ml), decreasing by 1230
      hours (22.6 +/- 5.9 ng/ml), with a further decrease at 1630 hours (12.3 +/- 3.1
      ng/ml). At all three time points, PAI-1 remained unchanged by the
      mineralocorticoid. Our results therefore do not support a major mineralocorticoid
      effect on PAI-1. However, our study does not exclude a modulatory role of F,
      since unchanged PAI-1 could be observed in spite of a marked suppression of the
      RAAS.

PMID- 11967824
TI  - Acute effects of ACE inhibition on coronary endothelial dysfunction.
AB  - The prerequisite of atherosclerosis, endothelial dysfunction, is characterised by
      impaired endothelium-dependent vasodilation caused by the reduced bioavailibility
      of nitric oxide (NO). In order to assess the role of acute ACE inhibition in this
      setting, coronary arterial endothelial function was quantified following acute
      intracoronary administration of the angiotensin-converting enzyme (ACE) inhibitor
      quinapril. Twenty-one patients with non-limiting coronary artery disease were
      studied before and after acute intracoronary administration of 10 mg quinapril.
      Nine patients received pre-treatment with the angiotensin AT(1)-receptor
      antagonist losartan (2 x 50 mg, p.o.). Coronary cross-sectional diameter was
      measured via quantitative angiography and microvascular reaction was investigated
      by intracoronary Doppler flow measurement during intracoronary infusion of 0.1 to
      10 micromol/l acetylcholine. Quinapril acutely improved endothelial dysfunction
      on the macro- as well as the microvascular level. Losartan did not alter
      macrovascular function but facilitated microvascular endothelial function. Acute
      quinapril application led to no further improvement of endothelial dysfunction in
      patients pre-treated with losartan. Acute quinapril infusion improved endothelial
      function in patients with coronary heart disease. Treatment with the AT(1)
      receptor antagonist losartan led to a slight improvement in microvascular
      endothelial function, but pre-treatment with losartan blunted the vascular effect
      of quinapril, suggesting that the combination of ACE inhibition and AT(1)
      receptor antagonism may not exert a synergistic benefical impact on the coronary
      vasculature.

PMID- 11967825
TI  - Should the use of short acting angiotensin-converting enzyme inhibitors be
      abandoned?
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitors (ACE-I) have different modes
      of action and different durations of inhibition. The effects of ACE-I on the
      various components of the renin-angiotensin system (RAS) at trough hours were
      studied in patients with diabetes mellitus receiving long-term ACE-I treatment.
      METHODS: Out of 86 Type 1 and 2 diabetic patients, 49 were untreated, 25 received
      captopril and 12 received enalapril as chronic treatment. Blood for the
      determination of plasma renin activity (PRA), serum ACE activity and plasma
      angiotensin II (Ang II) was drawn in the morning (0700-0900 hours) after an
      overnight fast, about 12 hours after the last dose. PRA and Ang II were measured
      by RIA and serum ACE activity was assayed by a radiometric assay using (3)H
      hippuryl-glycyl-glycine as a substrate. RESULTS: Mean age was significantly
      greater in the enalapril-treated patients. Systolic and diastolic blood pressures
      were not different between the captopril-treated and untreated groups. Serum ACE
      activity in the captopril-treated diabetic patients was 101.5+/-42.5 nmol/mL/min,
      values obtained in untreated diabetic patients (101.4+/-25.2 nmol/mL/min). In
      contrast, ACE activity in the enalapril-treated patients was significantly
      reduced (5.5+/-7.5 nmol/mL/min) compared with untreated and captopril-treated
      patients (p<0.00001). PRA values in the ACE-I treated patients were significantly
      increased. Plasma Ang II levels were significantly increased in the captopril
      treated vs. untreated patients (65.1+/-50.2 vs. 36.2+/-31.7 pg/mL, p=0.006),
      whereas the values in the enalapril-treated patient were slightly, but not
      significantly, reduced (23.8+/-21.4 pg/mL). CONCLUSIONS Trough serum ACE activity
      is not suppressed in diabetic patients receiving captopril, compared with those
      receiving enalapril and we thus question the use of short acting ACE-I in these
      patients.

PMID- 11967826
TI  - Angiotensin II binding and extracellular matrix remodelling in a rat model of
      myocardial infarction.
AB  - Clinical evidence points to a role for angiotensin II (Ang II) in the post
      infarction remodelling of cardiac hypertrophy. The present study was designed to
      investigate the remodelling process in an animal model of myocardial infarction
      (MI) using the following criteria: 1) histological studies to examine the re
      vascularisation process and collagen deposition in different regions of the
      myocardium; 2) histological evidence to investigate the cell type distribution
      using cell-specific markers; 3) histological and Western blot analysis to
      localise Ang II receptor subtypes (AT(1)-receptor and AT(2)-receptor) and to
      study their regulation; 4) kinetics of the binding of Ang II to its receptors in
      a heart perfusion model; and 5) to assess the effect of the Ang II antagonist
      (losartan) on these parameters. MI was induced by ligation of the left anterior
      descending coronary artery of Sprague-Dawley rats. Four different animal groups
      were established: 1) sham-operated, non-treated; 2) sham-operated, treated with
      losartan; 3) myocardial infarct, non-treated; and 4) myocardial infarct, treated
      with losartan. In infarcted rat hearts, fibroblasts and collagen types I and III
      increased in the remnant viable region of the left ventricle compared with sham
      operated rats. One month of losartan treatment in myocardial infarcted rats
      revealed insignificant changes in fibroblasts and collagen types I and III
      compared with sham controls. Also, myocardial infarction increased AT(1)-receptor
      protein levels compared with sham-operated controls, as judged by Western
      blotting. In losartan-treated myocardial infarct animals, no changes were
      detected at the level of AT(1)-receptor expression compared with non-treated
      myocardial infarct rats. Binding studies of Ang II on endothelial cell lining and
      directly on myocytes in sham-operated and infarcted perfused rat hearts revealed
      that, in myocardial infarcted-animals, Ang II binding affinity increased both in
      the endothelium and in myofibres. This may be considered a major putative effect
      of the peptide in potentiating the pharmacodynamics of hypertrophy. In losartan
      treated myocardial infarcted-animals, a marked increase in the binding affinities
      of Ang II for the AT(2)-receptor subtype was observed. Hence, potential
      cardioprotective effects of the AT(1)-receptor antagonist are proposed.

PMID- 11967827
TI  - The effect of angiotensin II on mitogen-activated protein kinase in human
      cardiomyocytes.
AB  - The role of angiotensin II (Ang II)-receptors on mitogen-activated protein kinase
      (MAPK) activation in cardiomyocytes remains controversial. Therefore, the current
      study was designed to investigate the actions of AT(1)- and AT(2)-receptors on
      Ang II-induced extracellular signal-regulated kinase (ERK), p38 and the c-Jun N
      terminal kinase (JNK) MAPK activities in human cardiomyocytes. Human cardiac
      tissue was obtained from open-heart surgery (n=6). The cardiac tissue was minced
      and incubated in the special tissue culture system for 24 hours in the absence or
      presence of Ang II (10(-7) M). These studies were repeated with the AT(1)
      receptor antagonist losartan (10(-6) M) or the AT(2)-receptor antagonist PD
      123319 (10(-6) M). Immunohistochemical staining and Western blot analysis with
      phospho-antibodies were performed to determine ERK, JNK and p38 activities. Ang
      II increased ERK and p38 activities in human cardiomyocytes. The effects of Ang
      II were abolished by losartan and enhanced by PD-123319. Co-incubation with both
      losartan and PD-123319 resulted in a decrease of ERK and p38 activities in
      cardiomyocytes. The immunohistochemical staining of JNK showed no significant
      differences between Ang II alone, Ang II plus losartan and Ang II plus PD-123319
      groups. In conclusion, Ang II has a potent effect on ERK and p38 MAPK activities
      in cardiomyocytes, by acting through AT(1)-receptors. This effect of Ang II is
      modified by AT(2)-receptors. Therefore, Ang II, via AT(1)- and AT(2)-receptor
      stimulation, has a distinct effect on MAPK activity in cardiomyocytes.

PMID- 11967828
TI  - Mutant analysis reveals complex regulation of sphingolipid long chain base
      phosphates and long chain bases during heat stress in yeast.
AB  - Sphingolipid long chain bases (LCBs) in Saccharomyces cerevisiae,
      dihydrosphingosine (DHS) and phytosphingosine (PHS) and their phosphates (DHS-P
      and PHS-P) are thought to play roles in heat stress. However, quantitative
      studies of LCBs and LCBPs have been limited by analytical methods. A new
      analytical procedure allowed us to measure changes in all known LCBPs and LCBs in
      wild-type and mutant cells during heat shock and to correlate the changes with
      heat stress resistance. All five molecular species of LCBPs increased rapidly but
      transiently when log and stationary phase cells were heat-stressed and when log
      phase cells were induced for thermotolerance, suggesting that LCBPs play a role
      in heat stress. In support of this hypothesis, cells lacking the minor LCB
      kinase, Lcb5p, but not the major kinase, Lcb4p, were two-fold less resistant to
      killing when log-phase cells were induced for thermotolerance. Thus, LCBPs seem
      to play a minor role in heat-stress resistance. However, their role may be masked
      by LCBs, which are elevated in mutant strains, such as one lacking Lcb4p. This
      elevation demonstrates that one function of Lcb4p is to regulate LCB levels. Two
      new compounds, C(16) DHS and C(16) DHS-P, were identified, with the latter being
      degraded by the Dpl1p lyase. Our data provide a basis for determining how the
      basal and heat-induced levels of individual species of LCBs and LCBPs are
      governed by the Lcb4p and Lcb5p kinases, the Dpl1p lyase and the Lcb3p
      phosphatase.

PMID- 11967829
TI  - A series of double disruptants for protein phosphatase genes in Saccharomyces
      cerevisiae and their phenotypic analysis.
AB  - Thirty-two protein phosphatase (PPase) genes were identified in Saccharomyces
      cerevisiae based on the nucleotide sequences of the entire genome. In an effort
      to understand the role of PPases and their functional redundancy in the cellular
      physiology of one of the reference eukaryotic organisms, a series of single and
      double PPase gene disruptants were constructed in the W303 strain background. Two
      single disruptants for the CDC14 and GLC7 genes were lethal. Double disruptants
      for 30 non-essential PPase genes were constructed in all possible 435
      combinations. No double disruptant showed synthetic lethality. Several phenotypes
      of the viable 30 single and 435 double disruptants were examined; temperature
      sensitive growth, utilization of carbon sources and sensitivity to cations and
      drugs. Four double disruptants exhibited synthetic phenotypes in addition to
      eight single ones: the pph21 pph22 double disruptant showed slow growth on
      complete medium, as did the sit4 and yvh1 single ones. In addition to the ptc1,
      ynr022c and ycr079w single disruptants, the ppz1 ppz2 double disruptant showed
      temperature-sensitive slow growth. The msg5 ptp2 double disruptant, like the
      ynr022c single one, did not grow on complete medium containing 0.3 M CaCl(2). The
      double msg5 ptc2 disruptant failed to grow on medium containing 1.0 M NaCl and,
      like the ynr022c single deletion, also could not grow on medium containing 0.3 M
      CaCl(2). The synthetic phenotypes in the two latter cases where each of the
      PPases is categorized in a different phosphatase family led us to discuss the
      novel mechanism involved in the functional redundancy of the PPases.

PMID- 11967830
TI  - The KlTrk1 gene encodes a low affinity transporter of the K+ uptake system in the
      budding yeast Kluyveromyces lactis.
AB  - Potassium uptake in Saccharomyces cerevisiae is mediated by at least two
      proteins, known as Trk1p and Trk2p. Direct involvement in cation movements has
      been demonstrated for Trk1p, which is the high affinity transporter. S.
      cerevisiae cells also show low affinity potassium uptake, perhaps mediated by
      Trk2p. Mutants lacking Trk1p, lose high affinity system, but when grown with
      moderate potassium concentrations, Trk2p seems to replace it. Mutants lacking
      both proteins are viable but require at least 10 mM K(+) in the medium to sustain
      growth. Here we report the cloning and characterization of a gene from
      Kluyveromyces lactis encoding a homologue of these two proteins. KlTrkp is a 1070
      amino acid peptide that shows, overall, higher homology with Trk2p than with
      Trk1p, and its disruption gives rise to cells with deficient potassium transport
      and with an increased K(+) requirement for normal growth. Determination of
      kinetic parameters in the K. lactis wild-type and Kltrk1Delta strains, as well as
      in Sctrk1Delta Sctrk2Delta S. cerevisiae cells expressing KlTrk1, indicated that
      this is a low affinity component of a major potassium uptake system in K. lactis.

PMID- 11967831
TI  - Construction of FLAG tagging vectors for Candida albicans.
AB  - We have constructed three new vectors for Candida albicans (pFLAG-Act1, pFLAG
      Mal2, and pFLAG-Met3). The proteins can be expressed as C-terminal FLAG-tagged
      proteins under the control of different promoters (ACT1, MAL2, and MET3). To
      confirm the protein expression, we used the Renilla reniformis luciferase and the
      drug efflux pump Cdr1p of Candida albicans as reporters. The luciferase protein
      expressed by the MET3 promoter was found to have the strongest activity of the
      three promoters when cultured in a methionine-depleted synthetic medium. Cdr1p
      was expressed as a C-terminal FLAG-tagged protein using either these vectors or
      PCR-mediated integration. The fluconazole resistance was increased by the Cdr1p
      expression in a CDR1 homozygous disruptant. The expressed proteins were detected
      by Western blotting using the anti-FLAG antibody. We also constructed a Cdr1p
      FLAG expressing strain, in which we directly tagged Cdr1p with FLAG on the genome
      loci, using a PCR-based integrative marker cassette that was amplified using the
      pFLAG vector. We then confirmed the protein expression by Western blotting. Thus,
      these new vectors are useful as C. albicans genetic tools.

PMID- 11967832
TI  - How many protein-coding genes are there in the Saccharomyces cerevisiae genome?
AB  - We have compared the results of estimations of the total number of protein-coding
      genes in the Saccharomyces cerevisiae genome, which have been obtained by many
      laboratories since the yeast genome sequence was published in 1996. We propose
      that there are 5300-5400 genes in the genome. This makes the first estimation of
      the number of intronless ORFs longer than 100 codons, based on the features of
      the set of genes with phenotypes known in 1997 to be correct. This estimation
      assumed that the set of the first 2300 genes with known phenotypes was
      representative for the whole set of protein-coding genes in the genome. The same
      method used in this paper for the approximation of the total number of protein
      coding sequences among more than 40 000 ORFs longer than 20 codons gives a result
      that is only slightly higher. This suggests that there are still some non-coding
      ORFs in the databases and a few dozen small ORFs, not yet annotated, which
      probably code for proteins.

PMID- 11967833
TI  - Copper adaptation and methylotrophic metabolism in Candida boidinii.
AB  - The importance of the antioxidant enzyme superoxide dismutase (CuZnSOD) in the
      metabolic switch from normotrophic to methylotrophic conditions was studied in
      the facultative methylotrophic yeast Candida boidinii. Copper adaptation was
      performed to qualify C. boidinii as a suitable cellular system to study the
      effect of induction of CuZnSOD, and other biochemical components along the copper
      detoxification system, on methanol adaptation. Copper adaptation results in the
      induction of CuZnSOD peroxidase activity as well as of glutathione. The effects
      at the metabolic level of exposure to both copper and methanol were also studied:
      the results suggest that the effect on antioxidant enzyme levels as a function of
      the change of trophic condition are predominant with respect to the effects of
      copper administration. Thus, the methanol-dependent induction of such enzymes is
      likely to provide a sufficient protection for the cells against toxic effects
      depending on copper administration. Administration of copper under methylotrophic
      conditions decreases the growth rate in spite of the high levels of antioxidant
      enzymes that are elicited by copper treatment. The adaptation to methanol
      metabolism was studied alsoafter methanol-independent induction of CuZnSOD,
      glutathione and catalase levels, obtained by exposure to high copper
      concentrations in glucose-containing medium. The metabolic changes induced by
      copper are persistent over several re-inoculations in normo-cupric glucose
      medium, thus allowing the study of the glucose-to-methanol switch on cells
      exhibiting high levels of antioxidant enzyme activities. Under such conditions
      the lag time observed during the transition from normotrophic to methylotrophic
      conditions is strongly reduced.

PMID- 11967835
TI  - Current awareness on yeast.

PMID- 11967874
TI  - The use of homework in psychotherapy: an introduction.

PMID- 11967834
TI  - Isolation and mapping of self-assembling protein domains encoded by the
      Saccharomyces cerevisiae genome using lambda repressor fusions.
AB  - Understanding how proteins are able to form stable complexes is of fundamental
      interest from the perspective of protein structure and function. Here we show
      that lambda repressor fusions can be used to identify and characterize homotypic
      interaction domains encoded by the genome of Saccharomyces cerevisiae, using a
      selection for polypeptides that can drive the assembly of the DNA binding domain
      of bacteriophage lambda repressor. Three high complexity libraries were
      constructed by cloning random fragments of S. cerevisiae DNA as lambda repressor
      fusions. Repressor fusions encoding homotypic interactions were recovered,
      identifying oligomerization units in 35 yeast proteins. Seventeen of these
      interaction domains have not been previously reported, while the other 18
      represent homotypic interactions that have been characterized at varying levels
      of detail. The novel interactions include several predicted coiled-coils as well
      as domains of unknown structure. With the availability of genomic sequences it
      should be possible to apply this approach, which provides information about
      protein-protein interactions that is complementary to that obtained from yeast
      two-hybrid screens, on a genome-wide scale in yeast or other organisms where
      large-scale protein-protein interaction data is not available.

PMID- 11967876
TI  - Improving homework compliance in the treatment of generalized anxiety disorder.
AB  - Generalized anxiety disorder is a chronic condition characterized by beliefs that
      worry prepares and protects, but that excessive worry is out of control. In this
      article, I review the cognitive-behavioral model of generalized anxiety, focusing
      specifically on problems related to excessive worrying. Noncompliance in self
      help homework is reflected in the patient's excessive focus on negative feelings,
      difficulty identifying automatic thoughts, demand for immediate results, and the
      belief that worries are realistic. Interventions for these problems are
      illustrated in the case of the treatment of a patient characterized by persistent
      worries, low self-confidence, procrastination, and avoidance.

PMID- 11967875
TI  - Using homework in therapy for depression.
AB  - There is a growing body of research evidence that demonstrates that completion of
      homework assignments is significantly correlated with outcome in cognitive
      therapy. The cognitive model of depression sees homework as an intrinsic aspect
      of the therapy process. Homework serves a number of purposes, including
      generalizing learning from the session into everyday life and fostering the
      independent practice of skills acquired during treatment. We review a number of
      commonly occurring problems that arise when seeking to engage the client in
      homework. The negotiation and implementation of homework assignments is a core
      clinical skill, and we present a range of strategies the clinician can use to
      optimize its effectiveness. It is vital that practitioners have an awareness of
      their own role and expectations in developing homework assignments.

PMID- 11967877
TI  - Modifying therapeutic homework for patients with personality disorders.
AB  - Generalizing therapeutic gains made during therapy sessions to patients' daily
      lives is the most fundamental goal of psychotherapy. Assigning between-session
      homework is an efficient method to teach new skills and to generalize those
      skills to the patient's natural environment. Given the persistent, chronic, and
      pervasive nature of the problems presented by the individual with a personality
      disorder, homework is not merely recommended but is an important and essential
      part of the therapeutic work. This article discusses modifying homework for
      personality-disordered patients in the context of a literature review and case
      examples from the various Personality Disorder Clusters. Also offered are a
      number of techniques to overcome patient "resistance."

PMID- 11967878
TI  - Showing you can do it: homework in therapy for children and adolescents with
      anxiety disorders.
AB  - This article discusses the application of homework tasks in an empirically
      supported treatment for children (aged 8-13 years) with anxiety disorders. Within
      this program, homework tasks-through practice and rehearsal in the child's
      natural environment-are an important ingredient to enable the child to increase
      his or her mastery of the information/skills covered in each session. The
      homework tasks also provide an opportunity for the therapist to check the child's
      grasp of the session content through unassisted application of the material. This
      article discusses issues that arise in the application of homework tasks with a
      child population (e.g., compliance). Homework in both child- and family-focused
      treatment is discussed. The issues addressed regarding homework, although raised
      in the context of anxious children in a cognitive behavioral treatment program,
      may be broadly applied to children in psychotherapy.

PMID- 11967879
TI  - Homework assignments in couple and family therapy.
AB  - Homework has been cited as an integral part of a number of theoretical
      orientations and therapy formats; unfortunately, very little has been written
      about its use with couples and families. This is despite the fact that many
      couple and family therapists espouse the use of homework or out-of-session
      assignments in order to help the effects of therapy jell. This article reviews
      some of the empirical literature on homework assignments and their effectiveness
      in the domain of therapy for families and couples. It also highlights the
      effectiveness of and the need for out-of-session assignments in treatment. A case
      illustration is used to demonstrate how homework assignments may be used as a
      significant change agent in couple and family treatment.

PMID- 11967880
TI  - Encouraging homework completion among older adults in therapy.
AB  - A growing body of research suggests that homework assignments facilitate positive
      outcomes in psychotherapy. We describe a cognitive behavioral outpatient therapy
      that stresses the important role homework plays in psychotherapy outcomes and
      that is found to be successful for treating emotional distress in both older
      adults and family caregivers. Just as a number of barriers can make it difficult
      for older clients to commit to regular therapy appointments, a variety of factors
      can also influence their completion of homework. We also address key issues
      frequently encountered when fostering homework compliance among older adults and
      utilize case vignettes to illustrate successful approaches to address these
      barriers. We present basic tenets for effective homework completion regardless of
      age group as well as several methods to address homework challenges that we find
      to be particularly pertinent for therapists treating today's older adults.

PMID- 11967881
TI  - Guidelines for enhancing homework compliance.
AB  - The ability to enhance compliance with therapeutic tasks such as homework may be
      a crucial therapeutic skill that determines the success of psychotherapy in real
      world clinical settings. This article presents guidelines for enhancing homework
      compliance through careful attention to: features of homework assignments, such
      as whether they are meaningful and doable and include a clear rationale and
      backup plan; and the therapist's manner when developing and reviewing homework
      assignments, such as whether that therapist is curious, collaborative, and
      reinforces all behavior that supports the homework's purposes. Clinical examples
      are used to illustrate the application of the guidelines.

PMID- 11967882
TI  - Reflecting on homework in psychotherapy: what can we conclude from research and
      experience?
AB  - This article examines the empirical basis of using homework in psychotherapy and
      then offers a synthesis of the research literature with the preceding clinical
      articles. We provide a practitioner-friendly review of psychotherapy process and
      outcome research literature, concluding that there is now sufficient evidence to
      support the assertion that homework assignments enhance psychotherapy outcomes.
      It is also clear that homework compliance is a consistently significant predictor
      of treatment outcome. Limitations of existing studies and future research
      directions are outlined, and we suggest that more specific questions are required
      regarding the integration of homework into therapy process. Clinical
      recommendations and issues in homework administration described in preceding
      articles are also synthesized. The research evidence and contributors to this
      issue converge in recommending homework within the broad context of psychotherapy
      and using creative ways of administering homework that is customized to the
      client.

PMID- 11967890
TI  - On counting and counting errors.
AB  - Counting objects in histological sections is often a necessary, sometimes an
      unexpected part of a research project. The recent literature shows that the
      subject of counting is of particular interest to readers of the Journal of
      Comparative Neurology but that it is also contentious and difficult. Even a brief
      review of past issues of the Journal shows that there are many misconceptions
      about counting and that there remain issues that have received little or no
      attention. Counts are subject to many errors. Some reports include readily
      recognizable errors, others fail to include all of the information that is needed
      for an evaluation of their accuracy. This review is above all a plea for adequate
      information about the methods used for counts in all publications. It serves to
      help those who are new to quantitative methods in histology; it considers some of
      the basic issues arising for anyone undertaking counts, or reviewing manuscripts
      that include counts. In particular, it considers recently introduced or re
      introduced counting methods that depend on accurate measures along the axis
      perpendicular to the plane of the sections, and looks at the difficulties
      inherent in these measures.

PMID- 11967891
TI  - Cortical and thalamic axon pathfinding defects in Tbr1, Gbx2, and Pax6 mutant
      mice: evidence that cortical and thalamic axons interact and guide each other.
AB  - During development, cortical areas establish precise reciprocal projections with
      corresponding thalamic nuclei. Pioneer axons from the cortex and thalamus first
      meet in the intermediate zone of the subcortical telencephalon (subpallium).
      Their close interactions in the subpallium suggest that they may use each other
      for guidance. To test this hypothesis, the development of corticothalamic and
      thalamocortical connections was studied in mice with mutations of transcription
      factor genes expressed specifically in the cortex (Tbr1), the dorsal thalamus
      (Gbx2), or both (Pax6). In Tbr1 mutants, cortical pioneer axons entered the
      subpallium at the appropriate time, but most stopped growing without entering the
      diencephalon. Surprisingly, thalamic axons (which do not express Tbr1) deviated
      into the external capsule and amygdala regions, without entering the cortex.
      Conversely, in most Gbx2 mutants, thalamic axons were reduced in number and grew
      no farther than the subpallium. Cortical axons (which do not express Gbx2) grew
      into the subpallium but did not enter the diencephalon. In one Gbx2- /- case,
      sparse thalamocortical and corticothalamic projections both developed, but in no
      case did one projection reach its target and not the other. In Pax6 mutants,
      neither corticothalamic nor thalamocortical axons reached their targets. These
      results suggest that thalamocortical and corticothalamic projections may not form
      independently. After reaching the subpallium, each projection may require a
      molecularly intact reciprocal projection for further guidance. This type of
      mechanism ensures that thalamocortical and corticothalamic axons project
      reciprocally. However, the exact nature of the interaction between cortical and
      thalamic pioneer axons remains to be elucidated.

PMID- 11967892
TI  - Pale cytochrome oxidase stripes in V2 receive the richest projection from macaque
      striate cortex.
AB  - Once the visual pathway reaches striate cortex, it fans out to a number of
      extrastriate areas. The projections to the second visual area (V2) are known to
      terminate in a patchy manner. V2 contains a system of repeating pale-thin-pale-
      thick stripes of cytochrome oxidase (CO) activity. We examined whether the patchy
      terminal fields arising from primary visual cortex (V1) projections are
      systematically related to the CO stripes in V2. Large injections of an
      anterograde tracer, [(3)H]proline, were made into V1 of both hemispheres in 5
      macaques. The resulting V2 label appeared in layers 2-6, with the densest
      concentration in layer 4. In 21/29 injections, comparison of adjacent flatmount
      sections processed either for autoradiography or CO activity showed that the
      heaviest [(3)H]proline labeling was located in pale CO stripes. In 7/29
      injections, there was no clear enrichment of labeling in the CO pale stripes. In
      1 injection, the proline label correlated with dark CO stripes. On a fine scale,
      CO levels vary within V2 stripes, giving them an irregular, mottled appearance.
      In all stripe types, the density of proline label would often wax and wane in
      opposing contrast to these local fluctuations in CO density. Our data showed that
      V1 input is generally anti-correlated with the intensity of CO staining in V2,
      with strongest input to pale stripes. It is known that the pulvinar projects
      preferentially to dark stripes. Therefore, V2 receives interleaved projections
      from V1 and the pulvinar. Because these projections favor different stripe types,
      they may target separate populations of neurons.

PMID- 11967893
TI  - Gonadal hormones are responsible for maintaining the integrity of spine synapses
      in the CA1 hippocampal subfield of female nonhuman primates.
AB  - It is well established that gonadal hormonal manipulation results in morphologic
      changes in the rat hippocampus. The great similarities in the hippocampal
      formation between nonhuman primates and humans, as well as the differences in
      this structure between humans and rats, led to this investigation of whether
      hormonal manipulation in female subhuman primates influences pyramidal cell spine
      density in the CA1 hippocampal subfield, as it does in rats. African green
      monkeys (Cercopithecus aethiops sabaeus) were ovariectomized, and half of the
      animals received estrogen replacement therapy. One month later, the monkeys were
      killed. In the first group of experiments, pyramidal cell spines were analyzed on
      Golgi-impregnated material taken from the CA1 hippocampal subfield. In the second
      experiment, unbiased electron microscopic stereologic calculations were performed
      to estimate the volumetric density of spine synapses in the same hippocampal
      subfield. Analysis of the Golgi-impregnated material showed that the spine
      density of CA1 pyramidal cells is much lower in the ovariectomized animals than
      in ovariectomized and estrogen-replaced monkeys. The unbiased, electron
      microscopic, stereologic calculation confirmed the light microscopic observation.
      The volumetric density (number of spine synapses/microm(3)) of spine synapses was
      significantly lower (43.33%) in the ovariectomized animals than in ovariectomized
      and estrogen-replaced monkeys. Because the hippocampus is involved in specific
      mnemonic functions, this observation highlights the importance of hormone
      replacement therapy in postmenopausal conditions.

PMID- 11967894
TI  - Experience-dependent plasticity of zinc-containing cortical circuits during a
      critical period of postnatal development.
AB  - Distinctive subsets of glutamatergic neurons in cerebral cortex sequester the
      transition metal zinc within the synaptic vesicles of their axon terminals. In
      the present study we used histochemical localization of synaptic zinc to
      investigate normal postnatal development and experience-dependent plasticity of
      zinc-containing circuits in somatosensory barrel cortex of rats. First, we found
      that zinc-containing cortical circuits are dynamically reorganized between
      postnatal day (P) 0 and P28. Whereas most cortical laminae exhibited
      idiosyncratic increases in zinc histochemical staining with advancing age, lamina
      IV barrels were darkly reactive early in life and then lost much of their
      complement of synaptic zinc during postnatal weeks 2-4. Second, we established
      that sensory experience plays a major role in sculpting the zinc-containing
      innervation of cortical barrels. Trimming a particular facial whisker arrested
      the normal postnatal decline in synaptic zinc in the corresponding, deprived
      barrel. This resulted in more intense zinc staining in deprived barrels compared
      with adjacent, nondeprived barrels. Notably, the influence of experience on
      development of zinc circuits was most robust during a critical period extending
      from about P14, when an effect of whisker trimming first could be observed,
      through P28, after which time chronic deprivation no longer resulted in
      heightened levels of synaptic zinc in lamina IV. These findings indicate that
      sensory input can have a marked influence on development of cortical circuits,
      including those within lamina IV, throughout the first postnatal month.

PMID- 11967895
TI  - Postnatal development of connectional specificity of corticospinal terminals in
      the cat.
AB  - The purpose of this study was to examine postnatal development of connectional
      specificity of corticospinal terminals. We labeled a small population of primary
      motor cortex neurons with the anterograde tracer biotinylated dextran amine. We
      reconstructed individual corticospinal segmental axon terminals in the spinal
      gray matter in cats of varying postnatal ages and adults. We found that at days
      25 and 35 the segmental termination field of reconstructed axons was large,
      estimated to cover more than half of the contralateral gray matter. Branches and
      varicosities were sparse and had a relatively uniform distribution. When we
      examined the terminal fields of multiple axons, reconstructed over the same set
      of spinal sections (120-200 microm), we found that there was extensive overlap.
      By day 55, the morphology and termination fields had changed remarkably. There
      were many short branches, organized into discrete clusters, and varicosities were
      preferentially located within these clusters. The termination field of individual
      axons was substantially reduced compared with that of younger animals, and there
      was minimal overlap between the terminals of neighboring corticospinal neurons.
      In adults, a further reduction was seen in the spatial extent of terminals,
      branching, and varicosity density. Termination overlap was not substantially
      different from that in PD 55 animals. Development of spatially restricted
      clusters of short terminal branches and dense axonal varicosities occurred just
      prior to development of the motor map in primary motor cortex and may be
      necessary for ensuring that the corticospinal system can exert a dominant
      influence on skilled limb movement control in maturity.

PMID- 11967896
TI  - Involvement of cyclin-dependent kinases in axotomy-induced retinal ganglion cell
      death.
AB  - We have tested the role of cyclin-dependent kinases (CDKs) in the type 3B death
      of axotomized retinal ganglion cells, by injecting intraocularly olomoucine,
      roscovitine, or butyrolactone I. Each of these inhibits CDK1, CDK2, and CDK5;
      CDK1 and CDK2 are involved in cell proliferation, whereas CDK5 is involved in
      neuronal differentiation. The inhibitors partially protected ganglion cells
      against the effects of axotomy. These agents may affect the ganglion cells
      directly, because CDK1, its regulatory subunit cyclin B1, and CDK5 were
      identified immunohistochemically in the perikarya of ganglion cells, and this was
      confirmed for CDK1 and CDK5 in Western blots of the ganglion cell layer. These
      blots showed an axotomy-induced phosphorylation of CDK5 occurring remarkably
      quickly (within 6 hours of axotomy) but little if any change in the
      phosphorylation state of CDK1. In addition, we studied the expression of
      proliferation markers, including proliferating cell nuclear antigen (PCNA) and
      the synthesis of DNA, by immunohistochemical and autoradiographic methods. Normal
      or axotomized ganglion cells did not express PCNA and did not synthesize DNA.
      Although we cannot exclude the possibility that axotomized ganglion cells may
      leave their quiescent state, our data show that they did not progress beyond the
      G1 phase of the cell cycle. Finally, in contrast to inhibitors of CDKs, cell
      cycle blockers with different targets than CDKs did not protect ganglion cells.
      Globally, our results suggest that axotomy-induced death of ganglion cells
      involves the activation of CDK1, CDK2, or CDK5 (most probably CDK5) but not the
      full cell cycle machinery.

PMID- 11967897
TI  - Cellular basis for the effects of substance P in the periaqueductal gray and
      dorsal raphe nucleus.
AB  - Substance P (SP) is known to act at supraspinal sites to influence pain
      sensitivity as well as to promote anxiety. The effects of SP could be mediated in
      part by actions in the periaqueductal gray (PAG) and the dorsal raphe nucleus
      (DRN), adjoining mesencephalic cell groups that are strategically positioned to
      influence both nociception and mood. Previous studies have indicated that SP
      regulates both enkephalin and serotonin neurotransmission in these brain regions.
      To determine the mechanism underlying the effects of SP in the PAG and DRN, the
      distribution of the principal receptor for SP, the neurokinin 1 (NK1) receptor,
      was examined with respect to other neurotransmitter markers. PAG neurons that had
      NK1 receptor immunolabeling were interdigitated with and received contacts from
      enkephalin-containing neurons. However, only a few (16/144; 11%) neurons with NK1
      receptor also contained enkephalin immunoreactivity after colchicine treatment.
      In the DRN, dendrites containing NK1 receptor were selectively distributed in the
      dorsomedial subdivision. The majority (132/137; 96%) of these dendrites did not
      contain immunoreactivity for the serotonin-synthesizing enzyme tryptophan
      hydroxylase. In contrast, neuronal profiles with NK1 receptor in both the PAG and
      the DRN often contained immunolabeling for glutamate. Light and electron
      microscopic examination revealed that 48-65% of cell bodies and dendrites with
      NK1 receptor were dually immunolabeled for glutamate. These data suggest that SP
      directly acts primarily on glutamatergic neurons in the PAG and DRN. To a lesser
      extent, enkephalin-containing neurons may be targeted. Through these actions, it
      may subsequently influence activity of larger populations of neurons containing
      enkephalin as well as serotonin. This circuitry could contribute to, as well as
      coordinate, effects of SP on pain perception and mood.

PMID- 11967898
TI  - Palliative surgery: a modern perspective.

PMID- 11967899
TI  - Relationship of clinical and pathologic response to neoadjuvant chemotherapy and
      outcome of locally advanced breast cancer.
AB  - BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy in locally advanced breast
      cancers produces histologically evaluable changes and frequently reduces the size
      of the primary tumor. Local clinical response to neoadjuvant chemotherapy may
      correlate with response of distant metastases. Therefore, clinical or
      pathological factors, which predict or assess response to treatment, may predict
      outcome after consideration for initial extent of disease. METHODS: To identify
      pretreatment characteristics of locally advanced breast cancers which predict
      clinical and pathologic response to neoadjuvant chemotherapy as well as survival
      and to assess the utility of postoperative histologic changes, we retrospectively
      studied one hundred forty-four patients with locally advanced breast cancer
      treated with neoadjuvant chemotherapy between January 1975 and July 1996.
      Patients were identified through pathology records of the Mount Sinai Medical
      Center and via one of the author's clinical databases. Pathologic and clinical
      responses to neoadjuvant chemotherapy were correlated with survival. Stepwise
      logistic regression was used to identify variables most significantly related to
      clinical response and pathologic axillary lymph node involvement. RESULTS:
      Complete clinical response with no palpable tumor was noted in 7/86 patients (8%)
      and complete pathologic response was achieved in 18/138 patients (13%). Both
      clinical (P = 0.038) and pathologic response (P = 0.011) were related to tumor
      size at the time of diagnosis: smaller tumors were more likely to respond to
      chemotherapy than larger tumors. Histologic evidence of chemotherapeutic effect,
      i.e., cytoplasmic vacuolization, change in the number of mitoses and localized
      fibrosis in lymph nodes did not correlate with clinical or pathologically
      measured response. Clinical and pathologic response was not associated with age,
      histology, differentiation, or type of chemotherapy. No residual tumor was found
      in the axillary nodes of 27% (37) of the patients. Age and complete pathologic
      response were the only variables significantly related to pathologic nodal
      status. Eighty-four percent of the 61 patients under 50 years of age had nodal
      involvement compared to 65% of older patients (P = 0.014). Fifty percent of
      complete pathologic responders had positive axillary lymph nodes compared to 76%
      of patients who did not have a complete pathologic response (P = 0.020). Distant
      disease-free (P = 0.039) and overall survival (P = 0.035) were related to the
      number of involved axillary lymph nodes. After consideration for pathologic lymph
      node status, no other variable was significantly related to distant disease-free
      or overall survival in multivariate analysis. No variable was significantly
      related to local disease-free survival. Age, clinical tumor size, clinical lymph
      node status, clinical response, type of chemotherapy, histology, differentiation,
      chemotherapy effects on primary tumor and lymph nodes, decline in the number of
      mitoses, and degree of fibrosis in nodes were not predictive of distant
      recurrence or overall survival. CONCLUSIONS: This study of patients treated with
      neoadjuvant chemotherapy for locally advanced breast cancers found little
      evidence that measurable clinical or pathologic changes attributable to
      chemotherapy predicted survival. Axillary lymph node status, associated with
      young age, was the most important prognostic indicator in these patients.

PMID- 11967900
TI  - Impact of patient age on the outcome of primary breast carcinoma.
AB  - BACKGROUND AND OBJECTIVES: The poorer outcome amongst younger breast cancer
      patients continues to be an issue of debate. In order to clarify the prognostic
      value of patient age, we retrospectively analyzed the data of 1098 breast cancer
      patients. METHODS: Patients were divided into two groups based on the age 35
      (Group I, women aged 35 or younger, and Group II, women aged over 35). Clinico
      pathological parameters, 10-year loco-regional recurrence-free (10LRRFS), distant
      relapse-free (10DRFS), and overall (10OS) survival estimates were determined.
      RESULTS: Among the 1098 patients, approximately 16.7% (183) were allocated to
      Group I and the other 83.3% (915) to Group II. There were no significant
      differences between the two groups in terms of histopathologic features or mean
      follow-up. Group I had a poorer 10LRRFS of 86.8% (P = 0.036), 10DRFS of 57.7% (P
      < 0.0001), and 10OS of 68.3% (P = 0.0001), compared with 93.9, 76.2, and 81.4%
      for Group II, respectively. Group I also showed a poorer 10DRFS when matched for
      stage and lymph node status as well. With lymph node status and tumor size, a
      patient age of younger than 35 was determined to be an independent prognostic
      factor by multivariate analysis. CONCLUSIONS: These results indicate that patient
      age (younger than 35) shows an independent prognostic value and that survival
      differences by age may reflect differences in the tumor biology.

PMID- 11967901
TI  - Primary non-Hodgkin lymphoma of the breast: The Mayo Clinic Experience.
AB  - BACKGROUND AND OBJECTIVES: To retrospectively evaluate the characteristics,
      natural history, results of treatment, and prognostic factors for patients
      diagnosed with primary breast lymphoma. METHODS: Between 1973 and 1998, 25 women
      and 1 man with the diagnosis of primary breast non-Hodgkin lymphoma (PNHLB) were
      seen at Mayo Clinic Rochester and Mayo Clinic Scottsdale. Patient
      characteristics, treatment methods, and outcome were analyzed. RESULTS: The
      median follow-up for surviving patients was 6.6 years (range: 1.8-22.1 years).
      There were 11 low-grade NHL, 13 intermediate-grade NHL, and 2 high-grade NHL.
      Three patients underwent mastectomy while 23 had local excision. The Ann Arbor
      stage of disease included: Stage I-21 patients, Stage II-5 patients. Sixteen
      patients received radiation after surgery (15 after biopsy, 1 after mastectomy).
      Chemotherapy was given to 10 patients as part of the initial treatment. Four
      patients with low-grade disease were treated with excision only. The 5-year
      overall survival rate was 70% and relapse-free survival rate 42%, while local
      control rate was 75% and distant control rate 51%. Five-year survival and relapse
      free survival rates for patients with low-grade disease were 91 and 61%,
      respectively. Three of four patients with low-grade disease treated with excision
      alone were free of local recurrence. For intermediate- and high-grade PNHLB, 5
      year survival rate was 61% for those treated with chemotherapy, compared to 31%
      for those without chemotherapy (P = 0.35), and the 5-year relapse-free survival
      rates were 49%, compared to 0%, respectively (P = 0.0017). Three patients with
      intermediate- or high-grade disease developed central nervous system (CNS)
      dissemination. On univariate analysis, Ann Arbor stage was the only significant
      prognostic factor for survival (P = 0.0021). CONCLUSIONS: The management of PNHLB
      should be based on histologic grade. Patients with low-grade disease may be
      managed with local therapy alone. The role of chemotherapy in this group is
      unclear. Patients with intermediate- or high-grade disease have better outcome if
      chemotherapy is included. An unusual site of distant dissemination for these
      patients is the CNS. The only significant prognostic factor for survival is Ann
      Arbor stage.

PMID- 11967903
TI  - Ex vivo sentinel lymph node biopsy in colorectal cancer: a feasibility study.
AB  - BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy may improve staging
      of colorectal cancer. We tested the feasibility of ex vivo SLN dissection.
      MATERIALS AND METHODS: Patients undergoing resection of a primary colorectal
      cancer were included in this study. SLN identification involved ex vivo injection
      of 1 cc isosulfan blue dye subserosally in the colon or submucosally in the
      rectum on a separate field. SLNs were cut at 2 mm intervals. Three hematoxylin
      and eosin-stained (HE) sections were prepared in addition to a middle level for
      cytokeratin immunostaining. RESULTS: Twenty-six patients with varying tumor
      location and stage were enrolled and the SLN was identified in 88% (23/26) cases.
      Three failures occurred in patients with rectal cancer. The average number of SLN
      harvested was 2.5. The status of the nodal basin was accurately predicted in 91%
      (21/23) of patients. Two false negative sentinel lymph nodes were harvested in 2
      of 3 patients with stage III/IV colorectal cancer. The SLN upstaged 2 patients as
      a result of HE stained step sections (n = 1) and immunostaining (n = 1).
      CONCLUSIONS: This data suggests that ex vivo SLN biopsy is feasible in colorectal
      cancer. Although ex vivo SLN biopsy does not alter the lymphatic dissection, it
      may upstage a subset of patients. The ex vivo technique may be less applicable in
      rectal cancer and false negative results may occur.

PMID- 11967905
TI  - Microsatellite analysis of fecal DNA for colorectal cancer detection.
AB  - BACKGROUND AND OBJECTIVES: The advent of noninvasive methods of testing for
      colorectal cancer that have a high level of specificity and sensitivity is
      eagerly awaited. METHODS: Thirty patients with sporadic colorectal cancer and 11
      patients with hereditary nonpolyposis colon cancer (HNPCC) enrolled in this
      study. We analyzed the loss of heterozygosity (LOH) in matched genomic DNA
      extracted from blood and surgical specimens (tumor and tumor-free colonic
      mucosa), and the corresponding oral rinse and stool specimens using seven
      microsatellite loci (APC, p53, DCC, hMLH1, D9S162, D9S171, and IFNA). To reduce
      the normal colonocyte DNA contamination of the stool samples, we compared three
      different methods for fecal genomic DNA extraction. As normal controls, we
      analyzed the LOH using the oral rinse and stool samples from 15 individuals
      without cancer. RESULTS: The LOH determined from the oral rinse and the stool
      samples matched those determined from the blood and the neoplastic tissue. All
      patients with HNPCC had microsatellite alterations at hMLH-1 in tumor DNA and
      corresponding fecal DNA. There were significant differences in the frequency of
      p53-LOH and D9S171-LOH between the group with sporadic disease and those with
      HNSCC (P = 0.0031 and 0.0294, respectively). Two cases with D9S162-LOH were
      detected in individuals without cancer. For the patients with sporadic disease,
      using p53 and adenomatous polyposis coli (APC), the sensitivity of the fecal DNA
      analysis was 96.7% (95% CI, 83-100) with a specificity of 100%. CONCLUSION: We
      demonstrate that LOH analysis using oral rinse and stool samples may be a
      suitable screening tool for colorectal cancer.

PMID- 11967906
TI  - Formalin instillation for refractory radiation-induced hemorrhagic proctitis.
AB  - BACKGROUND AND OBJECTIVES: Radiation proctitis is a common complication after
      pelvic irradiation. One to five percent of these patients will develop
      intractable or massive hemorrhagic radiation proctitis that will require repeated
      hospital admissions and blood transfusions. We evaluated the benefits of
      instillation of 4% formalin in the management of refractory hemorrhagic radiation
      induced proctitis. METHODS: From January 1998 to May 1999, 20 female patients who
      failed with administration of topical steroids and/or mesalazine were treated
      with 500 ml of 4% formalin instilled into the rectum in 50-ml aliquots. RESULTS:
      Median age was 58 years. Eighteen patients had cervical cancer and two,
      endometrial cancer. These patients received a mean of 7,500 rads to the pelvis.
      The symptoms began at a mean of 8 months after termination of radiotherapy.
      Median time of symptomatic rectal hemorrhage was 8 months. Median of blood units
      previously transfused was six (range: 2-11). Hemorrhage immediately ceased after
      the 4% formalin instillation in 17 patients. Three patients required formalin
      instillation repetition with success in one. Overall success was 90%. Median
      follow-up was 20 months. Five patients had moderate pelvic pain after
      instillation and one developed rectosigmoideal necrosis that required resection
      plus Hartmann procedure. Two patients developed rectovaginal fistula and required
      colostomy, and one thereafter, required abdominoperineal resection en bloc with
      the posterior wall of the vagina due to pelvis sepsis. CONCLUSIONS: Rectal
      instillation of 4% formalin is a simple, inexpensive, and efficient treatment for
      refractory hemorrhagic radiation proctitis.

PMID- 11967909
TI  - Costal chondritis after thoracoabdominal esophagectomy: how to prevent it.

PMID- 11967907
TI  - Significance of postoperative serum thyroglobulin levels in patients with
      papillary and follicular thyroid carcinomas.
AB  - BACKGROUND AND OBJECTIVES: Although there are many factors that affect
      postoperative serum levels of thyroglobulin (Tg), such levels have been
      previously used to detect recurrence of papillary and follicular thyroid
      carcinomas. This study was conducted to elucidate the significance of
      postoperative levels of Tg in patients with clinical presentations of papillary
      thyroid carcinoma, follicular thyroid carcinomas, or both. METHODS: To collect
      data pertaining to patients with thyroid cancer who were treated in Chang Gung
      Medical Center in Linkou, Taiwan, records relating to a total of 847 patients
      with pathologically verified papillary or follicular thyroid cancer, all of whom
      received total thyroidectomy and thyroid remnant ablation with radioactive iodide
      ((131)I), were studied. To evaluate the clinical significance of postoperative
      levels of Tg, the patients were categorized into three groups based on
      postoperative Tg level. Group A was classified as those demonstrating a 1-month
      postoperative Tg levels less than 1 ng/ml. Group B patients were classified as
      those displaying a 1-month postoperative Tg levels greater than or equal to 1
      ng/ml, but less than 10 ng/ml. Group C patients were classified as those
      exhibiting a 1-month postoperative Tg levels great than or equal to 10 ng/ml.
      RESULTS: Of the patients in group A, none presented with distant metastases at
      the time of diagnosis or during the follow-up period. In group B, 15 patients
      (3.5%) died of thyroid cancer. In this group, tumor size was an important factor
      in cancer-related mortality, diagnostic clinical class, and follow-up status. Of
      the 491 patients in group C, 49 (10.0%) patients died of thyroid cancer. Among
      the patients in group C, age, histopathologic type, stage of diagnosis, and
      follow-up Tg values were important factors. Among groups A, B, and C, there were
      161 (95.8%), 253 (76.4%), and 129 (37.1%) patients, respectively, with disease
      free status at the end of 1998. CONCLUSIONS: Postoperative serum Tg levels can be
      used as a prognostic indicator in patients with papillary and follicular thyroid
      cancer. For patients with Tg levels greater than or equal to 10 ng/ml, Tg levels
      are a useful marker to predict prognosis.

PMID- 11967908
TI  - Mutations in the von Hippel-Lindau (VHL) gene refine differential diagnostic
      criteria in renal cell carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Renal cell carcinomas (RCC) with abundant granular
      cytoplasm include oncocytomas, eosinophilic variants of chromophobe RCC,
      papillary RCC, collecting duct carcinoma, and some conventional (clear cell) RCC.
      Tumors with predominantly clear cell cytoplasm include typical chromophobe RCC
      and conventional (clear cell) RCC. The objective of this study was to determine
      if mutations in the VHL gene can serve as auxiliary diagnostic criteria in
      refining histology based subtyping of renal epithelial neoplasia. METHODS: The
      study cohort of 67 cases included 24 conventional RCC, 14 chromophobe RCC, 14
      papillary RCC, and 15 oncocytomas. Single strand conformational polymorphism
      (SSCP) was used as a screening procedure for mutations followed by automated
      sequencing to identify mutations. RESULTS: Thirteen of the 14 mutations
      identified were novel, seven of which were in the coding region. In chromophobe
      RCC, mutations clustered in the 5'UTR/promoter region and have not been
      previously reported. Exon 3 appeared to favor conventional (clear cell) RCC and
      correlated with a more aggressive phenotype. Mutations were absent in the
      papillary and oncocytoma RCC subtypes. CONCLUSIONS: Exon 3 mutations permitted a
      morphological distinction between conventional (clear cell) RCC and chromophobe
      RCC with clear cells. Mutations in the VHL gene refine histologic diagnostic
      criteria in RCC serving as adjuncts to the present morphology based diagnosis of
      RCC.

PMID- 11967911
TI  - Hyperthermic isolated hepatic perfusion for the treatment of unresectable cancers
      confined to the liver.

PMID- 11967916
TI  - Problems with informing women adequately about teratogen risk: some barriers to
      preventing exposures to known teratogens.

PMID- 11967913
TI  - Dose response in human teratology.

PMID- 11967915
TI  - Monitoring leflunomide (Arava) as a new potential teratogen.

PMID- 11967917
TI  - Putative new teratogens.

PMID- 11967918
TI  - Coarctation of the aorta and VSD: is there a reason for the association?

PMID- 11967919
TI  - Epidemiology of Down syndrome (Trisomy 21), Hawaii, 1986-97.
AB  - BACKGROUND: The live birth prevalence of Down syndrome is approximately 10 per
      10,000 live births in the United States. Down syndrome prevalence has been
      reported to change over time and to vary by selected demographic factors.
      METHODS: Data from a population-based birth defects registry in Hawaii involving
      363 Down syndrome cases delivered during 1986-97 were used to calculate overall
      prevalence and to investigate secular trends and differences by selected
      demographic factors. RESULTS: The total (live birth, fetal death, and elective
      termination) prevalence was 14.74 per 10,000 live births and fetal deaths. The
      unadjusted live birth prevalence was 8.67 per 10,000 live births. The adjusted
      live birth (live births and proportion of elective terminations expected to have
      resulted in live births) prevalence was 12.59 per 10,000 live births. No
      significant secular trends were observed for either total prevalence (P = 0.688)
      or adjusted live birth prevalence (P = 0.604). The total Down syndrome prevalence
      per 10,000 live births was highest for Far East Asians (22.01), followed by
      whites (17.06), Filipinos (15.94), and Pacific Islanders (9.21). Prevalence per
      10,000 births was higher in metropolitan Honolulu (18.57) than in the rest of
      Hawaii (14.15). After adjusting for maternal age, however, the differences within
      the demographic groups were not statistically significant. CONCLUSIONS: The live
      birth prevalence of Down syndrome in Hawaii during 1986-97 was lower than
      reported in the literature. Prevalence did not change significantly over time.
      Any differences in prevalence by maternal race/ethnicity and place of residence
      appeared to result from differences in maternal age distribution.

PMID- 11967920
TI  - Exencephaly in a subset of animals heterozygous for AP-2alpha mutation.
AB  - BACKGROUND: Transcription factor AP-2alpha has been implicated as a cell-type
      specific regulator of gene expression during vertebrate embryogenesis based on
      its expression pattern in neural crest cells, ectoderm, and the nervous system in
      mouse, chick, and frog embryos. AP-2alpha is prominently expressed in cranial
      neural crest cells, a population of cells migrating from the lateral margins of
      the neural folds during closure of the neural tube in E (embryonic day of
      development) 8-9 mouse embryos. Homozygous AP-2alpha mutant mice die perinatally
      with cranio-abdominoschisis, full facial clefting, and defects in cranial ganglia
      and sensory organs. METHODS: Mice heterozygous for the AP-2alpha mutation on a
      129/Sv strain were crossed with wildtype mice from the strain 129/Ola. The
      resulting embryos were genotyped, examined and used for histological analysis.
      RESULTS: A subset of animals heterozygous for the AP-2alpha mutation develop a
      midbrain exencephaly after the mutation was crossed for one generation in the
      129/Ola mouse strain. Up to 14% of the animals show a failure of the cranial
      neural folds to close resulting in a partial exencephaly, all of them being
      heterozygous for the mutation. The affected animals show reduced rostrocaudal
      dimensions of the skull and malformations of the bones of the cranial vault. The
      neural tube defects vary from pure midbrain exencephaly to a forebrain/midbrain
      exencephaly where the proliferating neural tissue covers the eyes completely.
      CONCLUSIONS: The results support a role of AP-2alpha in the etiology of
      exencephalic disorders. The phenotype observed might be due to a downregulation
      of the remaining allele suggesting the presence of an upstream modifier gene.

PMID- 11967921
TI  - Investigation of the effects of folate deficiency on embryonic development
      through the establishment of a folate deficient mouse model.
AB  - BACKGROUND: Folic acid (FA) has been shown to reduce the incidence of neural
      tube, craniofacial, and cardiovascular defects and low birth weight. The
      mechanism(s) by which the vitamin is effective, however, has not been determined.
      Therefore, a folic acid deficient mouse model was developed. METHODS: To create a
      folic acid deficiency, ICR female mice were placed on a diet containing no FA and
      including 1% succinyl sulfathiazole (SS) for 4 weeks before mating. Control mice
      were fed diets with either: 1) FA and 1% SS [+SS only diet]; 2) FA [normal diet];
      or 3) a breeding diet. Dams and fetuses were examined during various days of
      gestation. RESULTS: Blood analysis showed that by gestational day 18, plasma
      folate concentrations in the -FA+SS fed dams decreased to 1.13 ng/ml, a
      concentration approximately 3% of that in breeding diet fed dams (33.24 ng/ml)
      and 8% of that in +SS only/normal fed dams (13.59 ng/ml). RBC folate levels
      showed a similar decrease, whereas homocysteine concentrations increased.
      Reproductive outcome in the -FA+SS fed dams was poor with increased fetal deaths,
      decreased fetal weight, and delays in palate and heart development. CONCLUSIONS:
      Female mice fed a folic acid deficient diet and 1% succinyl sulfathiazole
      exhibited many of the characteristics common to human folic acid deficiency,
      including decreased plasma and RBC folate, increased plasma homocysteine, and
      poor reproductive outcomes. Thus, an excellent model has been created to
      investigate the mechanism(s) underlying the origin of birth defects related to
      folic acid deficiency.

PMID- 11967922
TI  - 2001 Warkany lecture: to die or not to die, the role of apoptosis in normal and
      abnormal mammalian development.
AB  - Cell death is a common and reproducible feature of the development of many
      mammalian tissues/organs. Two well-known examples of programmed cell death (PCD)
      are the cell deaths associated with fusion of the neural folds and removal of
      interdigital mesenchymal cells during digit formation. Like normal development,
      abnormal development is also associated with increased cell death in
      tissues/organs that develop abnormally after exposure to a wide variety of
      teratogens. At least in some instances, teratogens induce cell death in areas of
      normal PCD, suggesting that there is a link between programmed and teratogen
      induced cell death. Although researchers recognized early on that cell death is
      an integral part of both normal and abnormal development, little was known about
      the mechanisms of cell death. In 1972, Kerr et al. ('72) showed conclusively that
      cell deaths, induced in a variety of contexts, followed a reproducible pattern,
      which they termed apoptosis. The next breakthrough came in the 1980s when Horvitz
      and his colleagues identified specific cell death genes (ced) that controlled PCD
      in the roundworm, Caenorhabditis elegans (C. elegans). Identification of ced
      genes in the roundworm quickly led to the isolation of their mammalian
      homologues. Subsequent research in the 1990s led to the identification of a cadre
      of proteins controlling cell death in mammals, i.e., receptors/ligands, caspases,
      cytochrome c, Apaf-1, Bcl-2 family proteins, and IAPs. Two major pathways of
      apoptosis have now been elucidated, the receptor-mediated and the mitochondrial
      apoptotic pathways. The latter pathway, induced by a wide variety of toxic
      agents, is activated by the release of cytochrome c from mitochondria. Cytochrome
      c then facilitates the activation of a caspase cascade involving caspase-9 and 
      3. Activation of these caspases results in the cleavage of a variety of cellular
      proteins leading to the orderly demise of the cell. Work from my laboratory in
      the last 5 years has shown that teratogens, such as hyperthermia, 4
      hydroperoxycyclophosphamide, and staurosporine, induce cell death in day 9 mouse
      embryos by activating the mitochondrial apoptotic pathway, i.e., mitochondrial
      release of cytochrome c, activation of caspase-9 and -3, inactivation of poly
      (ADP-ribose) polymerase (PARP), and systematic degradation of DNA. Our work, as
      well as the work of others, has also shown that different tissues within the
      early post implantation mammalian embryo are differentially sensitive to the cell
      death inducing potential of teratogens, from exquisite sensitivity of cells in
      the developing central nervous system to complete resistance of cells in the
      developing heart. More importantly, we have shown that the resistance of heart
      cells is directly related to the failure to activate the mitochondrial apoptotic
      pathway in these cells. Thus, whether a cell dies in response to a teratogen and
      therefore contributes to the pathogenesis culminating in birth defects, depends,
      at least in part, by the cell's ability to regulate the mitochondrial apoptotic
      pathway. Future research aimed at understanding this regulation should provide
      insight not only into the mechanism of teratogen-induced cell death but also the
      role of cell death in the genesis of birth defects.

PMID- 11967923
TI  - Teratogen update: azathioprine and 6-mercaptopurine.

PMID- 11967950
TI  - Generation of monoclonal antibodies specific for human kallikrein 2 (hK2) using
      hK2-expressing tumors.
AB  - BACKGROUND: Human kallikrein 2 (hK2) and prostate-specific antigen (PSA) are
      serine proteases in the human kallikrein gene family that are 80% identical at
      the protein level. Like PSA, hK2 is expressed primarily in the prostate, making
      it an attractive bio-marker for prostate cancer development. In addition, its
      potent enzymatic activity may functionally affect the biology of prostate cancer.
      In order to further elucidate the possible roles of hK2 in prostate cancer, we
      have generated a panel of hK2-specific, non-PSA cross-reactive monoclonal
      antibodies. METHODS: A novel tumor-immunization strategy was used to produce
      monoclonal antibodies. Human hK2 cDNA was transfected into a BALB/c tumor cell
      line and used to immunize both BALB/c and PSA-expressing BALB/c.PSA transgenic
      mice. Because the BALB/c.PSA transgenic mouse showed a biased response towards
      hK2, a B cell fusion was performed using spleen cells from a transgenic mouse
      immunized in this fashion. RESULTS: A panel of monoclonal antibodies was produced
      and shown to be hK2-specific using newly developed hK2-specific sandwich ELISA
      and ELIspot assays. One of the monoclonal antibodies (6B7) was used to detect hK2
      in human prostate by immunohistochemistry. Interestingly, two of the antibodies
      affected the function of hK2. The 1F8 antibody enhanced the enzymatic activity of
      hK2 whereas the 3C7 antibody inhibited its function. CONCLUSIONS: These hK2
      specific antibodies illustrate a novel approach for constructing B-cell
      hybridomas and provide useful reagents to examine the role of hK2 in the biology
      and detection of prostate cancer.

PMID- 11967951
TI  - Human prostate cancer cell death by novel anticancer compounds, apoptosis
      inducing nucleosides from CD57+ HLA-DR(bright) natural suppressor cell line.
AB  - BACKGROUND: We validated the induction of apoptosis in human prostate cancer PC3
      cells by apoptosis-inducing nucleosides (AINs) released from the CD57(+)HLA
      DR(bright)-natural suppressor (57.DR-NS) cell line. We analyzed the molecular
      signaling pathway during AINs-induced apoptosis in PC3 cells. METHODS: Direct and
      indirect co-cultures between 57.DR-NS and PC3 cells were performed. AINs were
      isolated by high-performance liquid chromatography (HPLC) from 57.DR-NS cell
      cultures. Apoptosis in PC3 cells was analyzed by DNA fragmentation, sub-G(1) DNA
      content with flow cytometry, and terminal deoxynucleotide transferase-mediated
      dUTP nick end-labeling (TUNEL) method. The DNA strand breaks and activation of
      caspase-3 in PC3 cells were measured by DNA unwinding and flow cytometry assay.
      RESULTS: The 57.DR-NS cell line generated apoptosis in PC3 cells via AINs. AINs
      isolated from 57.DR-NS cell cultures induced apoptosis in PC3 cells. Furthermore,
      we found DNA strand breaks followed by activation of caspase-3 during AINs
      induced apoptosis in PC3 cells. CONCLUSIONS: The data obtained here indicated
      that AINs could induce apoptosis in PC3 cells through DNA strand breaks and
      activation of caspase-3.

PMID- 11967953
TI  - Gene expression signature of benign prostatic hyperplasia revealed by cDNA
      microarray analysis.
AB  - BACKGROUND: Despite the high prevalence of benign prostatic hyperplasia (BPH) in
      the aging male, little is known regarding the etiology of this disease. A better
      understanding of the molecular etiology of BPH would be facilitated by a
      comprehensive analysis of gene expression patterns that are characteristic of
      benign growth in the prostate gland. Since genes differentially expressed between
      BPH and normal prostate tissues are likely to reflect underlying pathogenic
      mechanisms involved in the development of BPH, we performed comparative gene
      expression analysis using cDNA microarray technology to identify candidate genes
      associated with BPH. METHODS: Total RNA was extracted from a set of 9 BPH
      specimens from men with extensive hyperplasia and a set of 12 histologically
      normal prostate tissues excised from radical prostatectomy specimens. Each of
      these 21 RNA samples was labeled with Cy3 in a reverse transcription reaction and
      cohybridized with a Cy5 labeled common reference sample to a cDNA microarray
      containing 6,500 human genes. Normalized fluorescent intensity ratios from each
      hybridization experiment were extracted to represent the relative mRNA abundance
      for each gene in each sample. Weighted gene and random permutation analyses were
      performed to generate a subset of genes with statistically significant
      differences in expression between BPH and normal prostate tissues. Semi
      quantitative PCR analysis was performed to validate differential expression.
      RESULTS: A subset of 76 genes involved in a wide range of cellular functions was
      identified to be differentially expressed between BPH and normal prostate
      tissues. Semi-quantitative PCR was performed on 10 genes and 8 were validated.
      Genes consistently upregulated in BPH when compared to normal prostate tissues
      included: a restricted set of growth factors and their binding proteins (e.g. IGF
      1 and -2, TGF-beta3, BMP5, latent TGF-beta binding protein 1 and -2); hydrolases,
      proteases, and protease inhibitors (e.g. neuropathy target esterase, MMP2, alpha
      2-macroglobulin); stress response enzymes (e.g. COX2, GSTM5); and extracellular
      matrix molecules (e.g. laminin alpha 4 and beta 1, chondroitin sulfate
      proteoglycan 2, lumican). Genes consistently expressing less mRNA in BPH than in
      normal prostate tissues were less commonly observed and included the
      transcription factor KLF4, thrombospondin 4, nitric oxide synthase 2A,
      transglutaminase 3, and gastrin releasing peptide. CONCLUSIONS: We identified a
      diverse set of genes that are potentially related to benign prostatic
      hyperplasia, including genes both previously implicated in BPH pathogenesis as
      well as others not previously linked to this disease. Further targeted validation
      and investigations of these genes at the DNA, mRNA, and protein levels are
      warranted to determine the clinical relevance and possible therapeutic utility of
      these genes.

PMID- 11967954
TI  - K+ channel currents in rat ventral prostate epithelial cells.
AB  - BACKGROUND: Electrophysiological function of the normal prostate has not been
      extensively studied. In particular, ion channel currents and their regulation
      have not been studied in freshly-isolated prostate cells. METHODS: Rat prostate
      secretory epithelial (RPSE) cells were isolated by collagenase treatment.
      Columnar epithelial cells were used for nystatin-perforated, whole-cell voltage
      clamp, and the intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured
      using fura-2. RESULTS: Step-like depolarizing pulses (900 msec) starting from -
      90 mV induced outwardly rectifying K(+) currents without inactivation. ACh (10
      microM) or ATP (100 microM) increased the outward current and hyperpolarized the
      cell membrane potential. Ionomycin (0.1 microM), a Ca(2+) ionophore, induced a
      similar increase in the outward current. TEA (5 mM), charybdotoxin (50 nM), and
      iberiotoxin (30 nM) inhibited the effect of ACh (or ATP) on the outward current,
      whereas apamin (100 nM) had no effect. The [Ca(2+)](i) of RPSE cells was
      increased by ACh, ATP, and UTP. CONCLUSIONS: RPSE cells have iberiotoxin
      sensitive Ca(2+)-activated K(+) channels that may play an important role in the
      exocrine secretions of the prostate.

PMID- 11967952
TI  - Differentiation and stromal-induced growth promotion of murine prostatic tumors.
AB  - BACKGROUND: We have derived a panel of p53-null prostatic "basal" and "luminal"
      epithelial cell lines and their ras transformed counterparts to study
      stromal/epithelial interactions and the properties of tumors arising from "basal"
      and "luminal" cells. METHODS: Previously derived normal murine prostatic "basal"
      epithelial (PE-B-1) and "luminal" epithelial (PE-L-1) cell lines were transformed
      with N-Ras. These lines and a spontaneously transformed "luminal" cell line were
      inoculated subcutaneously or orthotopically into athymic mice, alone or in
      combination with normal prostatic smooth muscle cells (SMC). RESULTS: All
      transformed lines formed subcutaneous tumors. SMC significantly enhanced the
      growth rate of the tumors arising from the "basal" and one of the "luminal" cell
      lines. The transformed "basal" line gave rise to tumors expressing both "basal"
      and "luminal" cytokeratins. CONCLUSIONS: Prostatic SMC promote the growth of
      transformed epithelial cells, suggesting that prostatic stroma may promote tumor
      development. Furthermore, transformed "basal" cells give rise to tumors
      containing "luminal" cells, suggesting that although most human tumors have a
      "luminal" phenotype, they may originate from transformed "basal" cells.

PMID- 11967955
TI  - Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer
      cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF
      kappaB activation.
AB  - BACKGROUND: The modulatory effects and molecular mechanisms of curcumin (CCM) on
      the cytotoxicity of chemotherapeutic agents to prostate cancer cells were
      explored. METHODS: The combined effects of CCM and chemotherapeutic agents were
      examined by three different administration schedules (one concurrent and two
      sequential treatments) in two androgen-independent prostate cancer (AIPC) cells
      (PC-3 and DU145). Alteration of cell cycle progression, protein levels, and
      transcriptional activation in PC-3 cells were assayed by flow cytometry, Western
      blotting, and gel shift assay, respectively. RESULTS: The combined effects of CCM
      --> chemotherapeutic agent schedule showed the greatest synergistic cytotoxicity
      when compared to the other two schedules in both cells. CCM induced a significant
      G1 arrest in PC-3, which may be mediated by the induction of p21(WAF1/CIP1) and
      C/EBPbeta. Moreover, CCM was able to inhibit both the constitutional and TNF
      alpha-induced NF-kappaB activation in a time-dependent manner. CONCLUSIONS: The
      incorporation of CCM into cytotoxic therapies may be a promising strategy for the
      treatment of AIPC.

PMID- 11967956
TI  - CAG polymorphic repeat lengths in androgen receptor gene among Japanese prostate
      cancer patients: potential predictor of prognosis after endocrine therapy.
AB  - BACKGROUND: Several investigators have examined the clinical significance of the
      length of the CAG repeat at the N-terminal region of the androgen receptor in the
      pathogenesis of prostate cancer. Because the clinical significance of CAG repeat
      length during the course of prostate cancer in Japanese patients is unknown, the
      present study analyzed CAG repeat length in relation to several potential
      clinical factors. MATERIALS AND METHODS: A total of 88 Japanese patients with
      prostate cancer and a control group of 53 patients with benign prostatic disease
      were enrolled in this study. The length of the CAG repeat was determined by PCR
      sequencing and analyzed in relation to several clinical factors. RESULTS: The
      length of the CAG repeat did not significantly differ between prostate cancer and
      benign prostatic disease. Although not statistically different with regard to
      clinical stage and serum PSA level, the CAG repeat length was associated with
      histological grade and age at diagnosis. In addition, the CAG repeat length in CR
      and in non CR patients significantly differed at 22.1 +/- 2.4 and 24.4 +/- 3.0,
      respectively (P = 0.0264), suggesting that the CAG repeat length can act as a
      molecular marker with which to predict response to endocrine therapy in stage D
      prostate cancer patients. CONCLUSIONS: A shorter CAG repeat length appears to
      predict a response to endocrine therapy, showing a positive prognostic value and
      indicating good prognosis in the metastatic stage of prostate cancer patients.

PMID- 11967986
TI  - Direct effect of a gonadotropin-releasing hormone agonist on the growth of canine
      mammary tumour cells.
AB  - Gonadotropin-releasing hormone (GnRH) agonist exert "in vivo" an inhibitory
      action on the growth of hormone-dependent canine mammary tumours (Lombardi et al.
      [1999] J. Vet. Pharmacol Ther. 22(1):56-61). The present experiments have been
      performed "in vitro" in order to investigate the mechanisms involved in this
      direct antiproliferative action of GnRH agonists. In particular, the aim was to
      study whether these compounds might exert their antiproliferative effect by
      interfering with the stimulatory action of epidermal growth factor (EGF). To this
      purpose, the effects of GnRH agonist, Goserelin (GnRH-A), on the mitogenic action
      of EGF, on EGF-activated intracellular signaling mechanisms (intracellular
      calcium and nitric oxide production) as well as on ATP induced cell proliferation
      and signalling, and on the binding of EGF receptors have been evaluated in
      primary culture of canine mammary tumour cells. The results of these "in vitro"
      studies show that GnRH-A counteracts the mitogenic action of EGF and ATP,
      decreases the EGF/ATP-induced calcium signalling and reduces EGF binding,
      probably by means of NO-induced [Ca2+]i downregulation. These data suggest that
      GnRH agonists may inhibit the proliferation of the tumour cells by interfering
      with the stimulatory action of EGF.

PMID- 11967987
TI  - Mapping of Sp1 regulation sites in the promoter of the human alpha1-proteinase
      inhibitor gene.
AB  - Keratoconus is a potentially blinding disease that thins the central cornea. In
      afflicted corneas, the level of an inhibitor, alpha1-proteinase inhibitor (alpha1
      PI), is found reduced. An increased expression of transcription factor Sp1 is
      also demonstrated. To examine the role of Sp1 in regulation of the human alpha1
      PI gene, a 1.4-kb (-1397/+9) 5'-flanking promoter sequence that contains 10 Sp1
      sites was cloned. Previous transient transfection experiments showed that Sp1
      expression indeed repressed the alpha1-PI promoter activity. In this study, 12
      DNA segments, a series of 5', 3', and internal deletions of the 1.4-kb alpha1-PI
      promoter sequence, were ligated into the SEAP (secreted alkaline phosphatase)
      reporter gene vector and transfected into human corneal stromal cells. Co
      transfection with a Sp1 expression vector pPacSp1 was also performed in parallel.
      The SEAP enzyme activity was assayed. A fragment with 489 bp (-480/+9) of the 3'
      sequence, and three fragments with internal deletions, were found to confer a
      majority of the full promoter activity. Other deletions significantly abolished
      the promoter activity. Site-directed mutagenesis experiments further revealed
      that the most proximal Sp1 site (-100/-87) may be an essential element involved
      in the negative regulation of alpha1-PI promoter activity by Sp1. Interaction
      between the proximal and distal Sp1 sites also seemed to be important. These
      results provide the first in-depth characterization of the transcription
      mechanisms regulating the expression of alpha1-PI. Mapping of the Sp1 sites may
      help elucidate the molecular pathway leading to the alterations observed in
      keratoconus.

PMID- 11967985
TI  - Effect of trichostatin A on human T cells resembles signaling abnormalities in T
      cells of patients with systemic lupus erythematosus: a new mechanism for TCR zeta
      chain deficiency and abnormal signaling.
AB  - Trichostatin A (TSA) is a potent reversible inhibitor of histone deacetylase, and
      it has been reported to have variable effects on the expression of a number of
      genes. In this report, we show that TSA suppresses the expression of the T cell
      receptor zeta chain gene, whereas, it upregulates the expression if its
      homologous gene Fc(epsilon) receptor I gamma chain. These effects are associated
      with decreased intracytoplasmic-free calcium responses and altered tyrosine
      phosphorylation pattern of cytosolic proteins. Along with these effects, we
      report that TSA suppresses the expression of the interleukin-2 gene. The effects
      of TSA on human T cells are predominantly immunosuppressive and reminiscent of
      the signaling aberrations that have been described in patients with systemic
      lupus erythematosus.

PMID- 11967988
TI  - von Hippel-Lindau tumor suppressor protein represses platelet-derived growth
      factor B-chain gene expression via the Sp1 binding element in the proximal PDGF-B
      promoter.
AB  - VHL is the causative gene for von Hippel-Lindau disease and sporadic clear cell
      renal cancer. It has been shown that pVHL can suppress the expression of certain
      genes that are overexpressed in renal carcinomas. One such gene is that encoding
      the potent mitogen and chemoattractant, platelet-derived growth factor B-chain
      (PDGF-B). The regulatory mechanisms underlying pVHL suppression of PDGF-B
      expression, however, are completely unknown. This understanding would shed vital
      light on the control of growth factor gene expression by this tumor suppressor.
      Here we report that pVHL can repress both endogenous steady-state PDGF-B mRNA
      expression and PDGF-B promoter-dependent transcription in WKY12-22 cells.
      Transient transfection analysis utilizing PDGF-B promoter-chloramphenicol acetyl
      transferase (CAT) reporter constructs revealed that pVHL inhibition of PDGF-B
      expression is mediated via the Sp1-binding element in the proximal region of the
      PDGF-B promoter. Recent studies have demonstrated a physical interaction between
      pVHL and Sp1, which activates the PDGF-B promoter. We show that Sp1 can rescue
      PDGF-B promoter activity and endogenous PDGF-B mRNA expression from pVHL
      repression. These findings thus demonstrate a pivotal role for Sp1 in pVHL
      inhibition of PDGF-B transcription.

PMID- 11967989
TI  - Interleukin-4 regulates connective tissue growth factor expression in human lung
      fibroblasts.
AB  - Transforming growth factor-beta (TGF-beta) and interleukin-4 (IL-4) have
      fibrogenic properties and induce extracellular matrix production in a variety of
      lung diseases. Connective tissue growth factor (CTGF) is a matrix signaling
      molecule stimulated by TGF-beta that in part mediates alpha1(I) collagen mRNA
      expression. In these studies, the regulation of CTGF expression by IL-4 in human
      lung fibroblasts was examined. Following 6 h of stimulation with IL-4, basal CTGF
      mRNA levels were unchanged as assessed by Northern blot analysis. However, IL-4
      attenuated the TGF-beta-stimulated induction of CTGF mRNA expression by 50%. This
      effect was selective because IL-4 did not affect fibronectin or alpha1(I)
      collagen mRNA expression induced by TGF-beta. Experiments employing the
      transcriptional inhibitor actinomycin D suggest that IL-4 did not affect the
      stability of the CTGF mRNA. Transient transfection assays with 3TP-Lux, a
      luciferase gene controlled by a TGF-beta inducible promoter, and with a CTGF
      promoter construct indicate that IL-4 interfered with the TGF-beta-induced
      transcriptional activation of the CTGF gene.

PMID- 11967990
TI  - NERF2, a member of the Ets family of transcription factors, is increased in
      response to hypoxia and angiopoietin-1: a potential mechanism for Tie2 regulation
      during hypoxia.
AB  - Vascular endothelial growth factor (VEGF) and angiopoietins regulate endothelial
      cell survival and migration and are essential for angiogenesis. Considerable
      progress has been made towards understanding hypoxia-mediated regulation of VEGF
      and its receptors. In contrast, little is known about the regulation of
      angiopoietins and their receptors in hypoxic cells. Using RT-PCR, RNAase
      protection assay, and Western blotting, we found that Tie1 and Tie2 mRNA and
      protein levels increased in response to hypoxia in human umbilical vein
      endothelial cells. Previously, we have shown that NERF2, a member of Ets family
      of transcription factors that is specifically expressed in endothelial cells,
      binds to the promoter region of Tie2 and transactivates Tie2 expression. In this
      study, we show that expression of NERF2 was increased under hypoxia and that this
      increase temporally correlated with the increase in Tie2 expression. Hypoxia
      induced expression of NERF2 and Tie2 was blocked by angiopoietin-2, a competitive
      inhibitor of angiopoietin-1, and by recombinant soluble extracellular domain of
      Tie2 but not by VEGF-neutralizing antibodies. In addition, angiopoietin-1
      directly induced expression of NERF2 in quiescent cells. These novel findings
      suggest that angiopoietin-1 regulates expression of NERF2 and its own receptor in
      hypoxic cells.

PMID- 11967991
TI  - Suppressive role of endogenous regucalcin in the enhancement of deoxyribonucleic
      acid synthesis activity in the nucleus of regenerating rat liver.
AB  - The role of endogenous regucalcin in the regulation of deoxyribonucleic acid
      (DNA) synthesis activity in the nuclei of regenerating rat liver after partial
      hepatectomy was investigated. The addition of regucalcin (0.25 and 0.5 microM) in
      the reaction mixture caused a significant decrease in the nuclear DNA synthesis
      activity of normal rat liver. This decrease was also seen in the presence of Ca2+
      chelator EGTA (0.4 mM), indicating that the effect of regucalcin is not related
      to nuclear Ca2+. Nuclear DNA activity was significantly increased in the presence
      of anti-regucalcin monoclonal antibody (10-50 ng/ml) in the reaction mixture. The
      effect was completely abolished by the addition of regucalcin (0.5 microM).
      Nuclear DNA synthesis activity was significantly increased at 24, 48, and 72 h
      after partial heptectomy. The effect of anti-regucalcin monoclonal antibody (25
      ng/ml) in increasing nuclear DNA synthesis activity was significantly enhanced at
      24 and 48 h after partial hepatectomy. The presence of staurospone (10(-6) M),
      trifluoperazine (2 x 10(-5) M), or PD98059 (10(-5) M) in the reaction mixture
      caused a significant decrease in DNA synthesis activity in the nuclei obtained at
      24 after partial hepateactomy. The effect of these inhibitors in the presence of
      anti-regucalcin monoclonal antibody (25 ng/ml) was greater than that in the
      absence of the antibody. The present study suggests that endogenous regucalcin
      plays a suppressive role in the enhancement of nuclear DNA synthesis activity in
      regenerating liver with cell proliferation after partial hepatectomy in rats.

PMID- 11967992
TI  - Signaling by the Mpl receptor involves IKK and NF-kappaB.
AB  - Binding of tumor necrosis factor-alpha (TNF-alpha) to its receptor activates IKK
      complex, which leads to inducement of NF-kappaB activity. Here we report that
      activation of Mpl ligand is also linked to IKK and NF-kappaB activity. Mpl
      ligand, also known as thrombopoietin (TPO) or megakaryocyte growth and
      development factor (MGDF), induces megakaryocyte differentiation and inhibition
      of mitotic proliferation, followed by induction of polyploidization and
      fragmentation into platelets. The latter process is often observed in
      megakaryocytes undergoing apoptosis. Treatment of a Mpl ligand-responding
      megakaryocytic cell line with this cytokine led to an immediate, transient
      increase in IKK activity followed by a profound decrease in this kinase activity
      over time. This decrease was not due to an effect on the levels of the IKK
      regulatory components IKKalpha and IKKbeta. Proliferating megakaryocytes
      displayed a constitutive DNA-binding activity of NF-kappaB p50 homodimers and of
      NF-kappaB p50-p65 heterodimers. As expected, reduced IKK activity in Mpl ligand
      treated cells was associated with a significant reduction in NF-kappaB DNA
      binding activity and in the activity of a NF-kappaB-dependent promoter. Our study
      is thus the first to identify a constitutive NF-kappaB activity in proliferating
      megakaryocytes as well as to describe a link between Mpl receptor signaling and
      IKK and NF-kappaB activities. Since a variety of proliferation-promoting genes
      and anti-apoptotic mechanisms are activated by NF-kappaB, retaining its low
      levels would be one potential mechanism by which inhibition of mitotic
      proliferation is maintained and apoptosis is promoted during late
      megakaryopoiesis.

PMID- 11967993
TI  - Relaxin activates the MAP kinase pathway in human endometrial stromal cells.
AB  - The reproductive hormone, relaxin, is structurally similar to insulin and insulin
      like growth factor (IGF). Although a number of cellular responses to relaxin have
      been described, intracellular signaling mechanisms that link relaxin receptor
      engagement to alterations in gene expression remain uncharacterized. In the
      present study, relaxin treatment of a well-characterized target, human
      endometrial stromal cells, resulted in rapid activation of p42/44 mitogen
      activated protein (MAP) kinase, as well as of MAPK (or ERK) kinase (MEK). Using a
      selective chemical inhibitor of MEK, it was further demonstrated that MEK
      phosphorylation is critical for relaxin-induced MAP kinase activation. Relaxin
      treatment also induced MAP kinase activation in THP-1 monocytic cells and in
      human smooth muscle cells, indicating that it may be a major signaling transducer
      utilized by the relaxin receptor. In contrast to insulin or IGF-1, relaxin did
      not trigger the PI 3-kinase/Akt pathway, perhaps accounting in part for relaxin's
      unique biological profile. Relaxin was also found to cause activation of the
      transcription factor CREB, a substrate of the MAP kinase pathway. Finally,
      activation of the MAP kinase pathway was shown to be essential for optimal
      stimulation of expression of the gene for vascular endothelial growth factor.

PMID- 11967995
TI  - Endogenous regucalcin suppresses the enhancement of protein phosphatase activity
      in the cytosol and nucleus of kidney cortex in calcium-administered rats.
AB  - The suppressive role of endogenous regucalcin (RC), which is a regulatory protein
      of calcium signaling, in the enhancement of protein phosphatase activity (PPA) in
      the cytosol and nucleus of kidney cortex in calcium-administered rats was
      investigated. Calcium content in the kidney cortex was significantly increased at
      0.5-5 h after a single intraperitoneal administration of calcium chloride
      solution (10 mg Ca/100 g body weight) to rats. The analysis with Western blotting
      of RC protein showed that RC levels in the cytosol and nucleus were significantly
      increased 0.5-5 h after the administration of calcium (10 mg/100 g). PPA toward
      phosphotyrosine, phosphoserine, and phosphothreonine was found in the cytosol and
      nucleus of kidney cortex. PPA toward three phosphoamino acids in the cytosol and
      nucleus was significantly increased by the administration of calcium (10 mg/100
      g). The presence of anti-RC monoclonal antibody (25 ng/ml) in the enzyme reaction
      caused a significant increase in PPA toward phosphotyrosine, phosphoserine, and
      phosphothreonine in the cytosol and nucleus of kidney cortex in normal rats. The
      effect of anti-RC monoclonal antibody (25 ng/ml) in increasing PPA toward three
      phosphoamino acids in the cytosol and nucleus was significantly enhanced in
      calcium-administered rats. The effect of anti-RC monoclonal antibody (25 ng/ml)
      in increasing PPA in the cytosol and nucleus of normal rats and calcium
      administered rats was completely abolished by the addition of RC (10(- 6) M) in
      the enzyme reaction mixture. The present study suggests that endogenous RC
      suppresses the enhancement of PPA in the cytosol and nucleus of kidney cortex in
      calcium-administered rats.

PMID- 11967994
TI  - Evidence for a pre-restriction point Cdk3 activity.
AB  - We have examined the activity of cyclin-dependent kinase 3 (cdk3) during G1-phase
      of the cell cycle in Chinese Hamster Ovary (CHO) fibroblasts. Histone H1 kinase
      activity associated with anti-cdk3 immunoprecipitates peaked during a brief
      window of time, 2-3 h prior to the restriction point. In vitro cdk3 activity was
      sensitive to roscovitine, a drug previously shown to inhibit cdks 1, 2, and 5,
      but not cdk4 or 6. Early G1-phase activation of cdk3 was downregulated by
      treatment of cells with MG132, an inhibitor of the proteasome, and by the protein
      synthesis inhibitor cycloheximide. These results provide evidence for a pre
      restriction point cdk3 activity that requires both the synthesis of a regulatory
      subunit and degradation of an inhibitor.

PMID- 11967997
TI  - Effects of Ginkgo biloba extract on the proliferation of vascular smooth muscle
      cells in vitro and on intimal thickening and interleukin-1beta expression after
      balloon injury in cholesterol-fed rabbits in vivo.
AB  - Restenosis may develop in response to cytokine activation and smooth muscle cell
      proliferation. Ginkgo biloba extract (EGb) has been used to treat cardiovascular
      and cerebrovascular diseases. In the present study, the effects of EGb on the
      growth of cultured vascular smooth muscle cells (VSMC), as well as on the
      expression of interleukin-1beta (IL-1beta) and the intimal response in balloon
      injured arteries of cholesterol-fed rabbits, were investigated. Using
      bromodeoxyuridine incorporation as an index of cell proliferation, EGb was found
      to inhibit serum-induced mitogenesis of cultured rat aorta VSMC in a dose
      dependent manner. In vivo, EGb and probucol ( positive control) reduced the
      atheroma area in thoracic aortas of male New Zealand white rabbits fed a 2%
      cholesterol diet for 6 weeks with balloon denudation of the abdominal aorta being
      performed at the end of the third week. Intimal hyperplasia, expressed as the
      intimal/medial area ratio, in the abdominal aortas was significantly inhibited in
      the both the EGb group (0.61 +/- 0.06) and the probucol group (0.55 +/- 0.03)
      compared to the C group (0.87 +/- 0.02). In the balloon-injured abdominal aorta,
      both EGb and probucol significantly reduced IL-1beta mRNA and protein expression
      and the percentage of proliferating cells. The inhibitory effects of EGb on the
      intimal response might be attributed to its antioxidant capacity. EGb may have
      therapeutic potential for the prevention of restenosis after angioplasty.

PMID- 11967998
TI  - Heat shock mediated modulation of protein kinase CK2 in the nuclear matrix.
AB  - Nuclear matrix, a key structure in the nuclear framework, appears to be a
      particularly responsive target during heat shock treatment of cells. We have
      previously shown that nuclear matrix is a preferential target for protein kinase
      CK2 signaling in the nucleus. The levels of CK2 in the nuclear matrix undergo
      dynamic changes in response to altered growth status in the cell. Here, we have
      demonstrated that CK2 targeting to the nuclear matrix is profoundly influenced by
      treatment of the cells to temperatures higher than 37 degrees C. Rapid increase
      in the nuclear matrix association of CK2 is observed when cells are placed at
      temperatures of 41 and 45 degrees C. This effect at 45 degrees C was higher than
      at 41 degrees C, and was time-dependent. Also, different cell lines behaved in a
      qualitatively similar manner though the quantitative responses differed. The
      modulations in the nuclear matrix associated CK2 in response to heat shock appear
      to be due to trafficking of the enzyme between cytosolic and nuclear
      compartments. In addition, it was noted that isolated nuclei subjected to heat
      shock also responded by a shuttling of the intrinsic CK2 to the nuclear matrix
      compartment. These results suggest that modulations in CK2 in the nuclear
      compartment in response to the heat stress occur not only by a translocation of
      the enzyme from the cytoplasmic compartment to the nuclear compartment, but also
      that there is a redistribution of the kinase within the nuclear compartment
      resulting in a preferential association with the nuclear matrix. The results
      support the notion that CK2 association with the nuclear matrix in response to
      heat shock may serve a protective role in the cell response to stress.

PMID- 11967996
TI  - Acrylamide disturbs the subcellular distribution of GABAA receptor in brain
      neurons.
AB  - Mechanisms underlying the action of acrylamide on neurons were studied by
      monitoring the expression of GABA(A) receptor (R) in cultured brain neurons
      derived from chicken embryos. In situ trypsinization of the neurons and 3H
      flunitrazepam binding assay were employed to examine the subcellular distribution
      of GABA(A)R. A 3-h exposure of the cultured neurons to 10 mM of acrylamide raised
      reversibly the proportion of intracellular (trypsin-resistant) 3H-flunitrazepam
      binding sites by about 48% and decreased cell surface binding 24% from respective
      control values, without altering total cellular binding and the affinity of the
      ligand. Moreover, the acrylamide treatment induced more intense perikaryal
      immunostaining of GABA(A)R alpha subunit proteins than that in control neurons
      but did not change the total level of cellular alpha immunostain, in accordance
      with the binding data. In the cell bodies of acrylamide-treated neurons, the
      level of neurofilament-200 kDa proteins was similar to control, whereas the
      tubulin protein content was significantly lowered approximately 51% from control,
      as revealed by quantifying the immunostained cytoskeletal elements. In addition,
      electron microscopic observations found reductions in the numbers of microtubules
      and neurofilaments in the perikarya of acrylamide-treated neurons. As exhibited
      by the 3H-leucine and 3H-monosaccharide incorporation experiments, the exposure
      to acrylamide inhibited the rate of general protein synthesis in the culture by
      21%, while the rate of glycosylation remained unaltered. Furthermore, in situ
      hybridization analysis showed that acrylamide did not modify the expression of
      GABA(A)R alpha subunit mRNAs. Taken together, these data suggest that acrylamide
      may downregulate the microtubular system and disintegrate neurofilaments, and
      thereby block the intracellular transport of GABA(A)R, resulting in the
      accumulation of intracellular receptors.

PMID- 11968000
TI  - Identification and characterization of a negative regulatory element within the
      epidermal growth factor receptor gene first intron in hormone-dependent breast
      cancer cells.
AB  - The epidermal growth factor receptor (EGFR) exhibits an inverse correlation with
      estrogen receptor (ER) expression in the majority of breast cancers, predicting a
      poor response to endocrine therapy and poor survival rate. Inappropriate
      overexpression of EGFR in breast cancer is associated with a more aggressive
      phenotype. Transcriptional regulation is the major regulatory mechanism
      controlling EGFR overexpression in breast cancer cells. We have identified a
      region within the first intron of the EGFR gene that mediates transcriptional
      repression of EGFR gene expression in ER +/low EGFR expressing but not in ER
      /high EGFR expressing breast cancer cells. Utilizing transient transfections of
      homologous and heterologous promoter-reporter constructs, we localized optimal
      repressive activity to a 96 bp intron domain. The 96 bp fragment displayed
      differential DNA-protein complex formation with nuclear extracts from ER + vs. ER
      breast cancer cells. Moreover, factors interacting with this intron negative
      regulatory element appear to be estrogen-regulated. Consequently, our results
      suggest that we have identified a potential mechanism by which maintenance of low
      levels of EGFR expression and subsequent EGFR upregulation may be attributed to
      the loss of transcriptional repression of EGFR gene expression in hormone
      dependent breast cancer cells.

PMID- 11968001
TI  - S111N mutation in the helical domain of human Gs(alpha) reduces its GDP/GTP
      exchange rate.
AB  - G-protein alpha subunits consist of two domains: a Ras-like domain also called
      GTPase domain (GTPaseD), structurally homologous to monomeric G-proteins, and a
      more divergent domain, unique to heterotrimeric G-proteins, called helical domain
      (HD). G-protein activation, requires the exchange of bound GDP for GTP, and since
      the guanine nucleotide is buried in a deep cleft between both domains, it has
      been postulated that activation may involve a conformational change that will
      allow the opening of this cleft. Therefore, it has been proposed, that
      interdomain interactions are playing an important role in regulating the
      nucleotide exchange rate of the alpha subunit. While constructing different
      Gs(alpha) quimeras, we identified a Gs(alpha) random mutant, which was very
      inefficient in stimulating adenylyl cyclase activity. The introduced mutation
      corresponded to the substitution of Ser(111) for Asn (S111N), located in the
      carboxi terminal end of helix A of the HD, a region neither involved in AC
      interaction nor in the interdomain interface. In order to characterize this
      mutant, we expressed it in bacteria, purified it by niquel-agarose
      chromatography, and studied its nucleotide exchange properties. We demonstrated
      that the recombinant S111N Gs(alpha) was functional since it was able to undergo
      the characteristic conformational change upon GTP binding, detected by the
      acquisition of a trypsin-resistant conformation. When the biochemical properties
      were determined, the mutant protein exhibited a reduced GDP dissociation kinetics
      and as a consequence a slower GTPgammaS binding rate that was responsible for a
      diminished adenylyl cyclase activation when GTPgammaS was used as activator.
      These data provide new evidence that involves the HD as a regulator of Gs(alpha)
      function, in this case the alphaA helix, which is not directly involved with the
      nucleotide binding site nor the interdomain interface.

PMID- 11967999
TI  - Basic fibroblast growth factor decreases elastin gene transcription in aortic
      smooth muscle cells.
AB  - The extracellular matrix (ECM) protein elastin plays an essential role in the
      cardiovascular system by imparting elasticity to blood vessel wall. In this
      study, we examined the effect of basic fibroblast growth factor (bFGF) on the
      expression of elastin in aortic smooth muscle cells (SMC) to gain insight into
      events associated with cardiovascular diseases. The results show that bFGF
      treatment of SMC causes a significant decrease in elastin mRNA and secreted
      tropoelastin levels. Nuclear run-on analyses demonstrate that the downregulation
      is due to a decrease in the level of elastin gene transcription. Transient
      transfections of SMC with wild-type and mutated elastin gene
      promoter/chloramphenicol acetyl transferase (CAT) constructs show that a
      previously identified activator protein-1-cAMP response element (AP1/CRE) (-564
      to -558-bp) within the elastin promoter mediates the bFGF-dependent
      downregulation of elastin gene transcription in SMC. Addition of bFGF to SMC
      activates the extracellular signal-regulated kinases 1/2 (ERK1/2) resulting in
      their translocation into the nucleus and subsequent induction of Fra-1. The
      addition of PD-98059, an inhibitor of ERK1/2 kinase, abrogates the bFGF-dependent
      decrease of elastin mRNA in SMC. The described inhibitory effect of bFGF on
      elastin gene expression in SMC may significantly contribute to the inefficient
      repair of elastin in early stages of vascular wall injury.

PMID- 11968003
TI  - Relative effects of VEGF-A and VEGF-C on endothelial cell proliferation,
      migration and PAF synthesis: Role of neuropilin-1.
AB  - Vascular endothelial growth factor (VEGF-A) is an inducer of endothelial cell
      (EC) proliferation, migration, and synthesis of inflammatory agents such as
      platelet-activating factor (PAF). Recently, neuropilin-1 (NRP-1) has been
      described as a coreceptor of KDR which potentiates VEGF-A activity. However, the
      role of NRP-1 in numerous VEGF-A activities remains unclear. To assess the
      contribution of NRP-1 to VEGF-A mediated EC proliferation, migration, and PAF
      synthesis, we used porcine aortic EC (PAEC) recombinantly expressing Flt-1, NRP
      1, KDR or KDR and NRP-1. Cells were stimulated with VEGF-A, which binds to Flt-1,
      KDR and NRP-1, and VEGF-C, which binds to KDR only. VEGF-A was 12.4-fold more
      potent than VEGF-C in inducing KDR phosphorylation in PAEC-KDR. VEGF-A and VEGF-C
      showed similar potency to mediate PAEC-KDR proliferation, migration, and PAF
      synthesis. On PAEC-KDR/NRP-1, VEGF-A was 28.6-fold more potent than VEGF-C in
      inducing KDR phosphorylation and PAEC-KDR/NRP-1 proliferation (1.3-fold),
      migration (1.7-fold), and PAF synthesis (4.6-fold). These results suggest that
      cooperative binding of VEGF-A to KDR and NRP-1 enhances KDR phosphorylation and
      its biological activities. Similar results were obtained with bovine aortic EC
      that endogenously express both KDR and NRP-1 receptors. In contrast, stimulation
      of PAEC-Flt-1 and PAEC-NRP-1 with VEGF-A or VEGF-C did not induce proliferation,
      migration, or PAF synthesis. In conclusion, the presence of NRP-1 on EC
      preferentially increases KDR activation by VEGF-A as well as KDR-mediated
      biological activities, and may elicit novel intracellular events. On the other
      hand, VEGF-A and VEGF-C have equipotent biological activities on EC in absence of
      NRP-1.

PMID- 11968002
TI  - Zinc suppresses IL-6 synthesis by prostaglandin F2alpha in osteoblasts:
      inhibition of phospholipase C and phospholipase D.
AB  - We previously reported that prostaglandin F2alpha (PGF2alpha) induces
      phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis
      by phospholipase D through heterotrimeric GTP-binding protein, resulting in the
      activation of protein kinase C (PKC) in osteoblast-like MC3T3-E1 cells and that
      PGF2alpha stimulates the synthesis of interleukin-6 (IL-6) via PKC-dependent
      p44/p42 mitogen-activated protein (MAP) kinase activation. In the present study,
      we investigated whether zinc affects the PGF2alpha-induced IL-6 synthesis in
      these cells. Zinc complex of l-carnosine (l-CAZ) dose-dependently suppressed the
      PGF2alpha-stimulated IL-6 synthesis. In addition, zinc alone reduced the IL-6
      synthesis. L-CAZ suppressed the PGF2alpha-induced p44/p42 MAP kinase
      phosphorylation. However, the p44/p42 MAP kinase phosphorylation induced by 12-O
      tetradecanoylphorbol-13-acetate (TPA), a direct activator of PKC, or NaF, a
      direct activator of GTP-binding protein, was not affected by l-CAZ. l-CAZ reduced
      the PGF2alpha-stimulated formation of inositol phosphates and choline. However, l
      CAZ did not affect the formation of inositol phosphates or choline induced by
      NaF. These results strongly suggest that zinc reduces PGF2alpha-induced IL-6
      synthesis via suppression of phosphoinositide-hydrolyzing phospholipase C and
      phosphatidylcholine-hydrolyzing phospholipase D in osteoblasts.

PMID- 11968005
TI  - Evidence for selective induction of phosphoenolpyruvate carboxykinase gene
      expression by unsaturated and nonmetabolized fatty acids in adipocytes.
AB  - Polyunsaturated fatty acids (PUFAs) and 3-thia fatty acids are hypolipidemic and
      decrease insulin resistance in Type II diabetic animals. To exert such an action,
      these FAs could decrease adipose tissue lipolysis or increase esterification.
      Glyceroneogenesis is an important metabolic pathway in adipocytes for re
      esterification of FAs originating from lipolysis and in hepatocytes for
      triacylglycerol synthesis during fasting. Cytosolic phosphoenolpyruvate
      carboxykinase (PEPCK) plays a key role in this pathway. Here we show that the
      PUFA docosahexaenoic acid (DHA) stimulates PEPCK mRNA in glucose-deprived adipose
      tissue explants from fed rats and in 3T3-F442A differentiated adipocytes. This
      effect is maximum at 3 h, stable up to at least 11 h of treatment, and affects
      the transcription of the gene. PEPCK mRNA half-life is not affected. Among a
      series of adipocyte transcripts, only the adipocyte lipid binding protein mRNA is
      also increased by DHA, although later than the PEPCK mRNA and at a much lower
      extent. DHA has no effect on PEPCK gene expression in the H4IIE hepatoma cells in
      which this gene is responsive to other inducers like cAMP. This lack of effect is
      not due to a failure of DHA to act in H4IIE cells since it induces the carnitine
      palmitoyltransferase 1 (CPT-1) mRNA. Therefore, the DHA effect appears to be cell
      selective. Results of experiments using either tetradecylthio acetic acid and
      alpha-bromopalmitate, two nonmetabolized Fas, or a series of inhibitors of FA
      metabolism show that the FA effect on PEPCK mRNA is not due to a product of its
      metabolism. Hence, polyunsaturated and nonmetabolized FAs stimulate adipose
      PEPCK, therefore potentially enhancing glyceroneogenesis and reducing FA output.
      This mechanism could participate in the hypolipidemic action of PUFAs.

PMID- 11968004
TI  - Phenotypic effects of continuous or discontinuous treatment with dexamethasone
      and/or calcitriol on osteoblasts differentiated from rat bone marrow stromal
      cells.
AB  - Osteoblasts are target cells for glucocorticoids and calcitriol, and their
      phenotype is greatly modified by these hormones. We investigated the effect of
      continuous or discontinuous hormonal exposure to osteoblasts derived from rat
      bone marrow stromal cells in long-term subcultures. Stromal cells were grown in
      primoculture in presence of dexamethasone (dex), but in following subcultures,
      dex and/or calcitriol were added just after seeding or after a 7-day hormone-free
      period. Cell proliferation, alkaline phosphatase (ALP) histochemical staining,
      and enzymatic bioactivity measurement, osteocalcin (OC), ALP and bone
      sialoprotein (BSP) mRNA expression were used to study the differential effect on
      osteoblastic phenotype of various conditions of treatment by dex and calcitriol.
      In primoculture, the osteoblastic differentiation was confirmed by the formation
      of calcified nodules and by strong expression of ALP, OC, and BSP mRNAs. In
      subcultures, proliferation of stromal cells was stimulated by dex and inhibited
      by calcitriol and by both hormones. Cell proliferation was not modified by
      hormonal lack during 7 days. Continuous hormonal treatment by dex strongly
      enhanced OC and BSP mRNAs, but apparently did not modified ALP mRNAs expression.
      Continuous treatment by calcitriol decreased ALP and the dex-induced BSP
      expression and stimulated the OC mRNAs level, strongly when associated with dex.
      The population of ALP+ cells and ALP bioactivity were strongly increased by dex,
      whereas calcitriol or both hormones decreased them. When the subcultures were
      undergone without hormonal treatment during 7 days, all osteogenic mRNAs strongly
      decreased even after hormonal recovery. Dex, calcitriol, and both hormones
      inhibited ALP mRNAs. OC messengers were only weakly detectable with both
      hormones. ALP+ cell population and ALP bioactivity were decreased after 14 days
      of hormonal treatment recovery. These results support that continuous presence of
      glucocorticoids appears as a major key for the permanent expression of the
      osteoblastic phenotype that is inhibited by calcitriol, in the rat bone marrow.

PMID- 11968006
TI  - Human papillomavirus-16 E7 protein inhibits the DNA interaction of the TATA
      binding transcription factor.
AB  - Previous studies have shown that the HPV-16 E7 protein interacts with TBP. This
      interaction was found to take place through residues in the carboxy terminal half
      of E7, mutation of which resulted in weaker transforming activity. In addition,
      binding of E7 to TBP was found to be increased following protein kinase CK2
      (casein kinase II) phosphorylation of E7, and mutation of this CK2 site also
      reduces E7's transforming activity. To date, however, there is no information on
      the effects of E7 upon TBP function. In order to address this we have performed a
      series of assays to investigate the effects of E7 upon the ability of human and
      S. pombe TBP to bind DNA. We show that HPV-16 E7 is indeed a potent inhibitor of
      TBP DNA binding activity. Further, this activity of E7 is increased following CK2
      phosphorylation of E7, consistent with it having an increased affinity for TBP.
      Finally, a mutant E7 protein defective in its ability to bind TBP, has no effect
      upon TBP binding to DNA. These results demonstrate that one consequence of the E7
      TBP interaction is abolition of TBP DNA binding activity, and may provide an
      explanation for the transcriptional inhibitory effects of E7.

PMID- 11968007
TI  - Release of cytokeratin-18 and -19 fragments (TPS and CYFRA 21-1) into the
      extracellular space during apoptosis.
AB  - Serum fragments of cytokeratins-18 and -19 (measured as TPS and CYFRA 21-1,
      respectively) have traditionally been considered as markers of tumor
      proliferation, although the evidence is scarce for a causative relationship
      between proliferation and levels of TPS and CYFRA 21-1. We examined whether
      apoptosis might produce TPS and CYFRA 21-1 fragments. MCF-7 breast cancer cells
      were treated with mitomycin C or agonistic anti-CD95 antibody, and levels of TPS
      and CYFRA 21-1 in tissue culture supernatants were compared with the frequency of
      cells exhibiting the following markers of cell death: intracellular cytokeratin
      18 cleavage, surface staining with annexin-V, propidium iodide uptake, DNA
      fragmentation. Twenty-four hours after inducing apoptosis, levels of TPS and
      CYFRA 21-1 were elevated > or = 4-fold in culture supernatants. Elevations in TPS
      and CYFRA 21-1 coincided with apoptosis measured by the first three cell death
      markers but preceded DNA fragmentation. These mitomycin C- and CD95-mediated
      elevations were completely inhibited by co-incubation with the caspase inhibitors
      Z-VAD.fmk and Z-IETD.fmk, respectively. We conclude that TPS and CYFRA 21-1 can
      be abundantly released into the extracellular space during the intermediate stage
      of epithelial cell apoptosis.

PMID- 11968008
TI  - Yeast methionine aminopeptidase type 1 is ribosome-associated and requires its N
      terminal zinc finger domain for normal function in vivo.
AB  - Methionine aminopeptidase type 1 (MetAP1) cotranslationally removes N-terminal
      methionine from nascent polypeptides, when the second residue in the primary
      structure is small and uncharged. Eukaryotic MetAP1 has an N-terminal zinc finger
      domain not found in prokaryotic MetAPs. We hypothesized that the zinc finger
      domain mediates the association of MetAP1 with the ribosomes and have reported
      genetic evidence that it is important for the normal function of MetAP1 in vivo.
      In this study, the intracellular role of the zinc finger domain in yeast MetAP1
      function was examined. Wild-type MetAP1 expressed in a yeast map1 null strain
      removed 100% of N-terminal methionine from a reporter protein, while zinc finger
      mutants removed only 31-35%. Ribosome profiles of map1 null expressing wild-type
      MetAP1 or one of three zinc finger mutants were compared. Wild-type MetAP1 was
      found to be an 80S translational complex-associated protein that primarily
      associates with the 60S subunit. Deletion of the zinc finger domain did not
      significantly alter the ribosome profile distribution of MetAP1. In contrast,
      single point mutations in the first or second zinc finger motif disrupted
      association of MetAP1 with the 60S subunit and the 80S translational complex.
      Together, these results indicate that the zinc finger domain is essential for the
      normal processing function of MetAP1 in vivo and suggest that it may be important
      for the proper functional alignment of MetAP1 on the ribosomes.

PMID- 11968009
TI  - Evidence that protein disulfide isomerase (PDI) is involved in DNA-nuclear matrix
      anchoring.
AB  - DNA-nuclear matrix (NM) anchoring plays a critical role in the organization of
      DNA within the nucleus and in functional access to DNA for transcription,
      replication, and DNA repair. The cellular response to oxidative stress involves
      both gene expression and DNA repair. We, therefore, determined if changes in the
      oxidative-reductive environment can affect DNA-NM anchoring. The present study
      used two approaches to study the effect of the reducing agent DTT on DNA-NM
      anchoring. First, the relative stringency of the DNA-NM attachment was determined
      by measuring the ability of NM attached DNA loops to undergo supercoiling
      changes. Second, the effects of DTT on the association of nuclear proteins with
      DNA were determined by cisplatin crosslinking. When nucleoids (nuclear matrices
      with attached DNA loops) were prepared from HeLa cells with 1 mM dithiothreitol
      (DTT), supercoiled DNA loops unwound more efficiently compared with control in
      the presence of increasing propidium iodide (PI) concentrations. In addition, the
      rewinding of DNA supercoils in nucleoids treated with DTT was inhibited. Both
      effects on DNA supercoiling ability were reversed by diamide suggesting that they
      are dependent on the oxidation state of the protein thiols. When DTT treated
      nucleoids were isolated from gamma-irradiated cells, the inhibition of DNA
      supercoil rewinding was equal to the sum of the inhibition due to DTT and gamma
      rays alone. Nucleoids isolated from heat-shocked cells with DTT, showed no
      inhibition of DNA rewinding, except a small inhibition at high PI concentrations.
      Nuclear DNA in DTT-treated nuclei was digested faster by DNase I than in
      untreated nuclei. These results suggest that DTT is altering DNA-NM anchoring by
      affecting the protein component(s) of the anchoring complex. Extracting NM with
      increasing concentrations of DTT did not solubilize any protein to a significant
      extent until measurable NM disintegration occurred. Therefore, we determined if 1
      mM DTT affected the ability of 1 mM cisplatin to crosslink proteins to DNA.
      Isolated nuclei were treated with 1 mM DTT for 30 min or left untreated prior to
      crosslinking with 1 mM cisplatin for 2 h at 4 degrees C. The ability of
      capsulation to crosslink DNA to proteins per se, did not appear to be affected by
      1 mM DTT because relative amounts of at least four proteins, 69, 60, 40, and 35
      kDa, were crosslinked to DNA to the same extent in DTT-treated and untreated
      nuclei. However, protein disulfide isomerase (PDI) crosslinked to DNA in
      untreated nuclei, but did not crosslink DNA in nuclei that were treated with 1 mM
      DTT; 1 mM DTT did not affect the intranuclear localization of PDI. Thus, DTT
      appears to alter the conformation of PDI, as suggested by the DTT-induced change
      in DNA association, but not its NM association. These results also imply that DNA
      NM anchoring involves the redox state of protein sulfhydryl groups.

PMID- 11968010
TI  - Augmented synthesis and differential localization of heparan sulfate
      proteoglycans in Duchenne muscular dystrophy.
AB  - Muscular dystrophies are characterized by continuous cycles of degeneration and
      regeneration that result in extensive fibrosis and a progressive diminution of
      muscle mass. Cell surface heparan sulfate proteoglycans are found almost
      ubiquitously on the surface and in the extracellular matrix (ECM) of mammalian
      cells. These macromolecules interact with a great variety of ligands, including
      ECM constituents, adhesion molecules, and growth factors. In this study, we
      evaluated the expression and localization of three heparan sulfate proteoglycans
      in the biopsies of Duchenne muscular dystrophy (DMD) patients. Through SDS-PAGE
      analyses followed by specific identification of heparitinase-digested proteins
      with an anti-Delta-heparan sulfate specific monoclonal antibodies, we observed an
      increase of three forms of heparan sulfate proteoglycans, corresponding to
      perlecan, syndecan-3, and glypican-1. Immunohistochemistry analyses indicated a
      differential localization for these proteoglycans: glypican-1 and perlecan were
      found mainly associated to ECM structures, while syndecan-3 was associated to
      muscle fibers. These results suggest that the amount of specific heparan sulfate
      proteoglycans is augmented in skeletal muscle in DMD patients presenting a
      differential localization.

PMID- 11968011
TI  - Estrogen and Myc negatively regulate expression of the EphA2 tyrosine kinase.
AB  - Estrogen receptor and c-Myc are frequently overexpressed during breast cancer
      progression but are downregulated in many aggressive forms of the disease. High
      levels of the EphA2 tyrosine kinase are consistently found in the most aggressive
      breast cancer cells, and EphA2 overexpression can increase metastatic potential.
      We demonstrate, herein, that estrogen and Myc negatively regulate EphA2
      expression in mammary epithelial cells. These data reveal EphA2 as a downstream
      target of estrogen and Myc and suggest a mechanism by which estrogen and Myc may
      regulate breast cancer.

PMID- 11968012
TI  - Vanadate protects human neuroblastoma SH-SY5Y cells against peroxynitrite-induced
      cell death.
AB  - We investigated the effect of vanadate, a tyrosine phosphatase inhibitor, on cell
      death induced by peroxynitrite in human neuroblastoma SH-SY5Y cells. Vanadate
      prevented cell death induced by 3-morpholinosydnonimine (SIN-1), a peroxynitrite
      donor; whereas SIN-1-induced cell death was not prevented by neither okadaic
      acid, an inhibitor of serine/threonine phosphatases 1 and 2A, nor cyclosporin A,
      an inhibitor of serine/threonine phosphatase 2B. Vanadate did not prevent cell
      death induced by N-ethyl-2-(1-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine, a
      nitric oxide donor. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase
      (PI3-kinase), did not block the protective effect of vanadate, suggesting that
      the protective effect of vanadate is independent on PI3-kinase. Vanadate
      increased tyrosine phosphorylation of several proteins including the focal
      adhesion protein p130 Crk-associated substrate (p130(cas)). By the treatment with
      SIN-1, the endogenous association of p130(cas) and Crk was disrupted, and the
      association was restored by vanadate treatment. These results suggest that
      disruption of tyrosine phosphorylation signaling may be critical for
      peroxynitrite-induced cell death, and that vanadate prevents cell death at least
      in part through the enhancement in tyrosine phosphorylation of the proteins
      including p130(cas).

PMID- 11968013
TI  - Soluble osteopontin inhibits apoptosis of adherent endothelial cells deprived of
      growth factors.
AB  - Osteopontin (OPN) is primarily an extracellular glycosylated phosphoprotein
      capable of stimulating cell migration and cell attachment, predominantly to
      mineralized surfaces. Found in moderate levels in plasma, it acts as a cytokine
      able to modify gene expression via integrins and certain CD44 isoforms. In this
      work we show that soluble OPN inhibits apoptosis of adherent human umbilical vein
      endothelial cells incubated in medium lacking critical growth factors and
      cytokines. In a dose-dependent manner OPN reduced the formation of apoptotic
      bodies and suppressed DNA fragmentation. OPN also caused an increase in Bcl-X(L)
      mRNA levels, suppressed the apparent dispersion of Bcl-X(L) throughout the
      cytoplasm, and slightly enhanced IkappaB-alpha protein degradation. These data
      suggest that a function of OPN in homeostatic processes is to facilitate the
      survival of stressed endothelial cells, possibly by occupying unligated integrins
      and suppressing integrin-mediated death.

PMID- 11968014
TI  - Real-time quantitative RT-PCR analysis of human bone marrow stromal cells during
      osteogenic differentiation in vitro.
AB  - We developed and used real-time RT-PCR assays to investigate how the expression
      of typical osteoblast-related genes by human bone marrow stromal cells (BMSC) is
      regulated by (i) the culture time in medium inducing osteogenic differentiation
      and (ii) the previous expansion in medium enhancing cell osteogenic commitment.
      BMSC from six healthy donors were expanded in medium without (CTR) or with
      fibroblast growth factor-2 and dexamethasone (FGF/Dex; these factors are known to
      increase BMSC osteogenic commitment) and further cultivated for up to 20 days
      with ascorbic acid, beta-glycerophosphate and dexamethasone (these factors are
      typically used to induce BMSC osteogenic differentiation). Despite a high
      variability in the gene expression levels among different individuals, we
      identified the following statistically significant patterns. The mRNA levels of
      bone morphogenetic protein-2 (BMP-2), bone sialo protein-II (BSP), osteopontin
      (OP) and to a lower extent cbfa-1 increased with culture time in osteogenic
      medium (OM), both in CTR- and FGF/Dex-expanded BMSC, unlike levels of alkaline
      phosphatase, collagen type I, osteocalcin, and osteonectin. After 20 days culture
      in OM, BMP-2, BSP, and OP were more expressed in FGF/Dex than in CTR-expanded
      BMSC (mRNA levels were, respectively, 9.5-, 14.9-, and 5.8-fold higher), unlike
      all the other investigated genes. Analysis of single-colony-derived strains of
      BMSC further revealed that after 20 days culture in OM, only a subset of FGF/Dex
      expanded clones expressed higher mRNA levels of BMP-2, BSP, and OP than CTR
      expanded clones. In conclusion, we provide evidence that mRNA levels of BMP-2,
      BSP, and OP, quantified using real-time RT-PCR, can be used as markers to monitor
      the extent of BMSC osteogenic differentiation in vitro; using those markers, we
      further demonstrated that only a few subpopulations of BMSC display enhanced
      osteogenic differentiation following FGF/Dex expansion.

PMID- 11968016
TI  - Human cell DNA replication is mediated by a discrete multiprotein complex.
AB  - A discrete high molecular weight multiprotein complex containing DNA polymerase
      alpha has been identified by a native Western blotting technique. An enrichment
      of this complex was seen at each step in its purification. Further purification
      of this complex by ion-exchange chromatography indicates that the peak of DNA
      polymerase alpha activity co-purifies with the peak of in vitro SV40 DNA
      replication activity eluting from the column. The complex has a sedimentation
      coefficient of 18S in sucrose density gradients. We have designated this complex
      as the DNA synthesome. We further purified the DNA synthesome by electroeluting
      this complex from a native polyacrylamide gel. The eluted complex retains in
      vitro DNA synthetic activity, and by Western blot analysis, contains DNA
      polymerase delta, proliferating cell nuclear antigen, and replication protein A.
      Enzymatic analysis of the electroeluted DNA synthesome indicates that the
      synthesome contains topoisomerase I and II activities, and SDS-PAGE analysis of
      the electroeluted DNA synthesome revealed the presence of at least 25 major
      polypeptides with molecular weights ranging from 20 to 240 kDa. Taken together,
      our evidence suggests that the DNA synthesome may represent the minimal DNA
      replication unit of the human cell.

PMID- 11968017
TI  - PKC-MEK-MAPK-dependent signal transduction pathway mediates the stimulation of
      lysyl oxidase expression by serum and PDGF in rat aortic smooth muscle cells.
AB  - Lysyl oxidase (LO) plays a critical role in the stabilization and
      insolubilization of fibrous structural proteins of the extracellular matrix and
      has been implicated in the suppression of Ras-induced tumorigenesis. Several
      prior reports demonstrate that the expression of this catalyst is strongly
      influenced by a variety of effectors of cell function and is responsive to the
      growth state of fibrogenic cells. Using specific inhibitors of components of
      signal transduction pathways, the present study reveals that a PKC-MEK-MAPK
      dependent pathway is critical to the enhanced expression of the LO gene in
      response to variations in the levels of the serum component of the growth medium
      and in response to platelet-derived growth factor (PDGF). PDGF is shown to be the
      major component of fetal bovine serum, which stimulates the activity of a LO
      promoter construct.

PMID- 11968015
TI  - Characterization of a TM-4 type tropomyosin that is essential for
      myofibrillogenesis and contractile activity in embryonic hearts of the Mexican
      axolotl.
AB  - A striated muscle isoform of a Tropomyosin (TM-4) gene was characterized and
      found to be necessary for contractile function in embryonic heart. The full
      length clone of this isoform was isolated from the Mexican axolotl (Ambystoma
      mexicanum) and named Axolotl Tropomyosin Cardiac-3 (ATmC-3). The gene encoded a
      cardiac-specific tropomyosin protein with 284 amino acid residues that
      demonstrated high homology to the Xenopus cardiac TM-4 type tropomyosin. Northern
      blot analysis indicates a transcript of approximately 1.25 kb in size. RT-PCR and
      in situ hybridization demonstrated that this isoform is predominantly in cardiac
      tissue. Our laboratory uses an animal model that carries a cardiac lethal
      mutation (gene c), this mutation results in a greatly diminished level of
      tropomyosin protein in the ventricle. Transfection of ATmC-3 DNA into mutant
      hearts increased tropomyosin levels and promoted myofibrillogenesis. ATmC-3
      expression was blocked in normal hearts by transfection of exon-specific anti
      sense oligonucleotide (AS-ODN). RT-PCR confirmed lower transcript expression of
      ATmC-3 and in vitro analysis confirmed the specificity of the ATmC-3 exon 2 anti
      sense oligonucleotide. These AS-ODN treated hearts also had a disruption of
      myofibril organization and disruption of synchronous contractions. These results
      demonstrated that a striated muscle isoform of the TM-4 gene was expressed
      embryonically and was necessary for normal structure and function of the
      ventricle.

PMID- 11968019
TI  - Chromatin of Trypanosoma cruzi: in situ analysis revealed its unusual structure
      and nuclear organization.
AB  - Chromatin of Trypanosoma cruzi is known to be organized in classical nucleosomal
      filaments, but surprisingly, these filaments do not fold in visible chromosomes
      and the nuclear envelope is preserved during cell division. Our hypothesis about
      the role of chromatin structure in regulating gene expression and, more
      generally, cell functioning, pressed us to verify if chromatin organization is
      modulated during the parasite life-cycle. To this end, we analyzed in situ the
      fine structural organization of T. cruzi chromatin by means of an integrated
      biophysical approach, using differential scanning calorimetry and fluorescence
      microscopy. We observed that logarithmic forms exhibit a less condensed chromatin
      with respect to the stationary ones. Thermal analysis revealed that parasite
      chromatin is organized in three main levels of condensation, barring from the
      polynucleosomal filament till to superstructured fibers. Besides, the
      fluorescence images of nuclei showed a characteristic chromatin distribution,
      with defined domains localized near to the nuclear envelope. While in stationary
      parasites, these regions are highly condensed, in logarithmic forms they unfold
      by extending themselves toward the center of nucleus. These observations suggest
      that, in comparison with higher eukaryotes, in T. cruzi the nuclear envelope
      plays an unusual and pivotal role in interphase and in mitosis.

PMID- 11968018
TI  - Regulation of tumor invasion and metastasis in protein kinase C epsilon
      transformed NIH3T3 fibroblasts.
AB  - Protein kinase C epsilon is an oncogenic, actin nucleating protein that
      coordinately regulates changes in cell growth and shape. Cells constitutively
      expressing PKCepsilon spontaneously acquire a polarized morphology and extend
      long cellular membrane protrusions. Here we report that the regulatory C1 domain
      of PKCepsilon contains an actin binding site that is essential for the formation
      of elongate invadopodial-like structures, increased pericellular
      metalloproteinase activity, in vitro invasion of a Matrigel barrier, and the
      invasion and metastasis of tumors grown in vivo by PKCepsilon-transformed NIH3T3
      fibroblasts in nude mice. While removing this small actin binding motif caused a
      dramatic reversion of tumor invasion, the deletion mutant of PKCepsilon remained
      oncogenic and tumorigenic in this experimental system. We propose that PKCepsilon
      directly interacts with actin to stimulate polymerization and the extension of
      membrane protrusions that transformed NIH3T3 cells use in vivo to penetrate and
      degrade surrounding tissue boundaries.

PMID- 11968020
TI  - Global chimeric exchanges within the intracellular face of the bradykinin B2
      receptor with corresponding angiotensin II type Ia receptor regions: generation
      of fully functional hybrids showing characteristic signaling of the AT1a
      receptor.
AB  - The intracellular (IC) face of the G-protein coupled receptors (GPCR), bradykinin
      (BK) B2 and angiotensin (AT) 1a, is similar in sequence homology and in size.
      Both receptors are known to link to Galphai and Galphaq but differ markedly in a
      number of physiologic actions, particularly with respect to their hemodynamic
      action. We made single as well as multiple, global replacements within the IC of
      BKB2R with the corresponding regions of the AT1aR. When stably transfected into
      Rat-1 cells, these hybrid receptors all bound BK with high affinity. Single
      replacement of the intracellular loop 2 (IC2) or the distal 34 residues of the C
      terminus (dCt) with the corresponding regions of AT1aR resulted in chimera, which
      turned over phosphotidylinositol (PI) and released arachidonic acid (ARA) as WT
      BKB2R. In contrast, incorporation of the AT1aR IC3 in a single replacement
      abolished signal transduction. However, the simultaneous exchange of IC2 and IC3
      of BKB2R with AT1aR resulted in a receptor responding to BK with PI turnover and
      ARA release approximately 4-fold greater than WT BKB2R. Likewise, the
      simultaneous replacement of IC2 and dCt resulted in a 2.8- and 1.6-fold increase
      in PI turnover and ARA release, respectively. In contrast, the dual replacement
      of IC3 and dCt could not overcome the deleterious effects of the IC3 replacement,
      resulting in very low PI activation and ARA release. Replacement of all three IC
      domains (IC2, IC3, and dCt) resulted in PI closer to that of AT1aR than BKB2R.
      The uptake of the receptor chimeras was similar to that of WT BKB2R with the
      exception of the IC3/dCt dual mutant, which exhibited very poor internalization
      (18% at 60'). When transfected into Rat-1 cells, the AT1aR markedly increased the
      expression of connective tissue growth factor (CTGF) mRNA, while BK slightly
      decreased it. The dual IC2/dCt and triple IC2/IC3/dCt hybrids both upregulated
      CTGF mRNA in response to BK. These results show that the IC face of the BKB2R can
      be exchanged with that of AT1aR, producing hybrid receptors, which take on the
      functional characteristics of AT1aR. The characterization of the chimera with
      stepwise replacement of the IC domains should allow for assignment of specific
      roles to the individual loops and C-terminus in the signaling and internalization
      of the BKB2R and facilitate the generation of a receptor with BKB2R binding and
      AT1aR function.

PMID- 11968021
TI  - Displacement of histamine from liver cells and cell components by ligands for
      cytochromes P450.
AB  - Intracellular histamine (HA) and cytochrome P450 monooxygenases (P450) each have
      been proposed as mediators of cell function, growth, and proliferation. The P450
      family of heme enzymes is found in virtually all cells and generates, transforms,
      or inactivates steroids and other lipids that participate in cell regulation. We
      previously demonstrated a second messenger role for HA in blood platelets and the
      formation of a HA-P450 heme complex when exogenous HA was added to microsomes
      isolated from rat liver cells or to purified human P450 isozymes. Employing a
      radioimmunoassay, we now demonstrate that rat liver slices, microsomes derived
      from the livers of adult male rats and mast cell-deficient mice, and hepatoma
      cells, all contain endogenous HA. HA release from microsomes into the incubation
      medium, as determined by radioimmunoassay, is enhanced in the presence of carbon
      monoxide, steroids, and certain drugs, all agents that unite either directly with
      the iron atom or bind elsewhere within the heme cavity. Rat liver slices
      preincubated with (3)H-HA release labeled amine into the medium in the presence
      of those same ligands. These findings provide evidence of an in situ HA-P450
      complex and offer further support that the imidazole, HA, is a physiological,
      intracellular modulator of cytochromes P450 in liver cells, and perhaps of these
      and other heme proteins in tissues in general.

PMID- 11968022
TI  - Leptin stimulates human osteoblastic cell proliferation, de novo collagen
      synthesis, and mineralization: Impact on differentiation markers, apoptosis, and
      osteoclastic signaling.
AB  - Anabolic hormones, mechanical loading, and the obese protein leptin play separate
      roles in maintaining bone mass. We have previously shown that leptin, as well as
      its receptor, are expressed by normal human osteoblasts. Consequently, we have
      investigated how leptin affects proliferation, differentiation, and apoptosis of
      human osteoblasts. Iliac crest osteoblasts, incubated with either leptin (100
      ng/ml), calcitriol (1,25(OH)(2)D(3); 10(-9) M) or 1-84 human parathyroid hormone
      (PTH; 10(-8) M), were cultured for 35 consecutive days and assayed for expression
      of various differentiation-related marker genes (as estimated by RT-PCR), de novo
      collagen synthesis, proliferation, in vitro mineralization, and osteoclast
      signaling. The effects of leptin on protection against retinoic acid (RA; 10(-7)
      M) induced apoptosis, as well as transition into preosteocytes, were also tested.
      Leptin exposure enhanced cell proliferation and collagen synthesis over both
      control condition and PTH exposure. Leptin inhibited in vitro calcified nodule
      production after 1-2 weeks in culture, however, subsequent to 4-5 weeks, leptin
      significantly stimulated mineralization. The mineralization profile throughout
      the entire incubation period was almost undistinguishable from the one induced by
      PTH. In comparison, 1,25(OH)(2)D(3) generally reduced proliferation and collagen
      production rates, whereas mineralization was markedly enhanced. Leptin exposure
      (at 2 and 5 weeks) significantly enhanced the expression of TGFbeta, IGF-I,
      collagen-Ialpha, ALP, and osteocalcin mRNA. Leptin also protected against RA
      induced apoptosis, as estimated by soluble DNA fractions and DNA laddering
      patterns subsequent to 10 days of culture. The expression profiles of Bax-alpha
      and Bcl-2 mRNAs indicated that leptin per se significantly protected against
      apoptosis throughout the entire incubation period. Furthermore, the osteoblast
      marker OSF-2 was diminished, whereas the CD44 osteocyte marker gene expression
      was stimulated, indicating a transition into preosteocytes. In terms of
      osteoclastic signaling, leptin significantly augmented the mRNA levels of both
      interleukin-6 (IL-6) and osteoprotegerin (OPG). In summary, continuous leptin
      exposure of iliac crest osteoblasts, promotes collagen synthesis, cell
      differentiation and in vitro mineralization, as well as cell survival and
      transition into preosteocytes. Leptin may also facilitate osteoblastic signaling
      to the osteoclast.

PMID- 11968024
TI  - Remodeling of sperm chromatin after fertilization involves nucleosomes formed by
      sperm histones H2A and H2B and two CS histone variants.
AB  - The composition of nucleosomes at an intermediate stage of male pronucleus
      formation was determined in sea urchins. Nucleosomes were isolated from zygotes
      harvested 10 min post-insemination, whole nucleoprotein particles were obtained
      from nucleus by nuclease digestion, and nucleosomes were subsequently purified by
      a sucrose gradient fractionation. The nucleosomes derived from male pronucleus
      were separated from those derived from female pronucleus by immunoadsorption to
      antibodies against sperm specific histones (anti-SpH) covalently bound to
      Sepharose 4B (anti-SpH-Sepharose). The immunoadsorbed nucleosomes were eluted,
      and the histones were analyzed by Western blots. Sperm histones (SpH) or
      alternatively, the histones from unfertilized eggs (CS histone variants), were
      identified with antibodies directed against each set of histones. It was found
      that these nucleosomes are organized by a core formed by sperm histones H2A and
      H2B combined with two major CS histone variants. Such a hybrid histone core
      interacts with DNA fragments of approximately 100 bp. It was also found that
      these atypical nucleosome cores are subsequently organized in a chromatin fiber
      that exhibits periodic nuclease hypersensitive sites determined by DNA fragments
      of 500 bp of DNA. It was found that these nucleoprotein particles were organized
      primarily by the hybrid nucleosomes described above. We postulate that this
      unique chromatin organization defines an intermediate stage of male chromatin
      remodeling after fertilization.

PMID- 11968023
TI  - Analysis of regulator of G-protein signaling-2 (RGS-2) expression and function in
      osteoblastic cells.
AB  - Regulator of G-protein signaling-2 (RGS-2) belongs to a novel family of GTPase
      activating proteins that rapidly turn-off G-protein coupled receptor signaling.
      RGS proteins contain a characteristic RGS domain by which they interact with the
      alpha-subunit of G-proteins and drive them into their inactive GDP-bound forms.
      Previously, we have reported that RGS-2 mRNA is rapidly and transiently increased
      by PTH in rat bone and in osteoblast cultures in vitro. In this study, we further
      explored the molecular basis for the regulation of RGS-2 by cloning and
      functionally characterizing the RGS-2 gene promoter. We cloned 2.3- and 2.8-kb
      fragments of the 5'-flanking regions of the rat and mouse RGS-2 genes,
      respectively, and generated a stable clone of UMR106 osteoblastic cells
      containing the rat RGS-2 promoter driving the beta-gal reporter gene (p2.3RGS-2
      beta-gal). Treatment of the stable clone with PTH resulted in a maximal 2.2- to
      3.6-fold increase in promoter activity at 8 h, reminiscent of the early response
      observed with endogenous RGS-2 mRNA regulation. Further, PTH (1-38), (1-31),
      PTHrP (1-34), and forskolin, which elevate cAMP levels, stimulated the promoter,
      while PTH (3-34) and (7-34), which do not readily stimulate cAMP accumulation,
      and PMA that directly activates protein kinase C, had no effect on promoter
      activity. Taken together, these results implicate the involvement of the
      Galpha(s)-adenylate cyclase-protein kinase A pathway in stimulating RGS-2
      expression. Maintenance of a hyperphosphorylated state via the inhibition of type
      2A protein phosphatases by okadaic acid, resulted in a strong dose-dependent
      increase in transcriptional activity of the RGS-2 promoter as well as that of the
      endogenous RGS-2 gene. Furthermore, overexpression of the osteoblast-specific
      transcription factor Runx2 also led to a stimulation of RGS-2 promoter activity.
      Functional analysis using RGS-2 overexpression suggests the potential negative
      regulatory effects of RGS-2 on PTH- and forskolin-induced cAMP production in
      osteoblastic cells. In summary, our data suggest that PTH treatment results in a
      direct transcriptional stimulation of RGS-2 that in turn may play a role in
      modulating the duration/intensity of PTH receptor signaling.

PMID- 11968048
TI  - Superoxide dismutase activities of spermatozoa and seminal plasma are not
      correlated with male infertility.
AB  - Abnormal reactive oxygen species (ROS) production is associated with defective
      sperm function. Superoxide dismutase (SOD) is related with the scavenging of
      seminal ROS. We aimed to determine the effect of SOD activities of spermatozoa
      and seminal plasma on sperm quality. Semen samples from infertile couples who
      consented to the analyses were divided into two groups: 1) normospermia (n = 20);
      and 2) oligoasthenozoospermia (n = 31). The SOD activities of the spermatozoa and
      seminal plasma were measured by determining the inhibition of pyrogallol
      autoxidation. The SOD activities of spermatozoa and seminal plasma in both groups
      were compared. The relationships between the SOD activities and the sperm
      qualities were determined. We noted that SOD activities of sperm/seminal plasma
      in both groups were nonsignificantly different (group 1 vs. 2 = 0.77 +/-
      0.33/0.84 +/- 0.40 U/mg protein for sperm, and 0.66 +/- and 0.36/0.83 +/- 0.47
      U/ml for seminal plasma). SOD activities of sperm/seminal plasma were positively
      but nonsignificantly correlated with the sperm motility (SOD of sperm = 0.0008 x
      motility + 0.67; SOD of seminal plasma = 0.0006 x motility + 0.81) and
      concentration (SOD of sperm = 0.0006 x concentration + 0.67; SOD of seminal
      plasma = 0.0021 x concentration + 0.73). We concluded that SOD activities of
      sperm and seminal plasma were nonsignificantly correlated with the seminal
      quality. It appears that the SOD survey is not a useful tool for determining
      sperm fertilization potential.

PMID- 11968047
TI  - Polymorphisms for interleukin-4 (IL-4) -590 promoter, IL-4 intron3, and tumor
      necrosis factor alpha -308 promoter: non-association with endometriosis.
AB  - Interleukin-4 (IL-4) is a cytokine with anti-inflammatory properties. Tumor
      necrosis factor alpha (TNF-alpha), a pluripotent proinflammatory cytokine, plays
      an important role in the process of numerous inflammatory and autoimmune
      diseases. We aimed to investigate whether gene polymorphisms for the IL-4 -590
      promoter, IL-4 intron3 and TNFalpha -308 promoter could be used as markers of
      susceptibility in endometriosis. The subjects, 226 premenopausal Taiwan Chinese
      women with surgically diagnosed endometriosis and nonendometriosis, were divided
      into two groups: 1) endometriosis (n = 120) and 2) nonendometriosis (n = 106).
      Polymorphisms for the IL-4 -590 promoter, IL-4 intron3, and TNFalpha -308 G-to-A
      promoter were detected by polymerase chain reaction (PCR). Genotypes and allelic
      frequencies for these gene polymorphisms in both groups were compared. We
      observed no significant differences in genotype distribution and allele frequency
      of the IL-4 -590 promoter, IL-4 intron3, and TNFalpha gene polymorphism between
      both groups. The proportions of the -590*C homozygote/heterozygote/-590* T
      homozygote for the IL-4 promoter in both groups were 1.6/31.6/66.6% in group 1,
      and 5.8/33.0/61.2% in group 2. The proportions of the RP1
      homozygote/heterozygote/RP2 homozygote for IL-4 intron3 in both groups were
      62.5/34.1/2.5% (group 1), and 64.1/32.0/3.9% (group 2). The proportions of -308*A
      homozygote/heterozygote/-308*G homozygote for the TNFalpha promoter in both
      groups were 7.5/20.8/71.7% (group 1), and 7.5/17/75.5% (group 2). We concluded
      that there is no association between endometriosis and the IL-4 and TNFalpha gene
      polymorphisms. The IL-4 -590 promoter, IL-4 intron3, and TNFalpha -308 G-to-A
      polymorphisms are not useful markers for predicting susceptibility to
      endometriosis.

PMID- 11968049
TI  - Use of the EIE-recombinant-Chagas-biomanguinhos kit to monitor cure of human
      Chagas' disease.
AB  - We used the EIE-Recombinant-Chagas-Biomanguinhos kit (EIE-Rec kit) developed by
      the Oswaldo Cruz Foundation, Brazil, to monitor cure of chagasic patients who
      were treated during the acute phase of T. cruzi infection. Treated patients were
      previously studied by parasitological and serological tests and classified as
      cured patients (CP) (n = 10), dissociated patients (DP) (n = 6), and noncured
      patients (NCP) (n = 6). When sera of these patients were assayed by EIE-Rec kit
      all sera from NCP and all sera from CP showed positive and negative reactions,
      respectively. These results were in full agreement with those obtained previously
      by the classical tests. Two DP showed a positive reaction; the remaining four
      displayed a negative reaction, similar to that observed in sera from nonchagasic
      (NCh) individuals, and could therefore be considered CP. Our results suggest that
      the EIE-Rec kit could be used to monitor the efficacy of Chagas' disease
      treatment.

PMID- 11968051
TI  - Comparison of four enzyme immunoassays for the detection of immunoglobulin G
      antibody against glomerular basement membrane.
AB  - Goodpasture syndrome is a life-threatening autoimmune kidney and pulmonary
      disease that is characterized by pulmonary hemorrhage, renal failure, and the
      presence of autoantibodies against glomerular basement membrane (GBM) by indirect
      fluorescent antibody (IFA) techniques. In 1988, these antibodies were found to be
      specific for the noncollagen region of the alpha3 collagen IV chain. The antigen
      is characterized by a restricted tissue distribution occurring mainly in the
      kidneys and lungs. Specific enzyme immunoassays (EIAs) for anti-GBM have now been
      developed for in vitro diagnostic use in the laboratory. Our objective in this
      study was to compare the results obtained using four different EIAs for detecting
      anti-GBM IgG antibody with those using the standard IFA method using tissue from
      human kidney. Thirty-two patients with suspected Goodpasture syndrome, and 10
      control sera were included in the study. GBM EIAs were purchased from or donated
      by the following vendors: Scimedx Corporation (Denville, NJ), INOVA Diagnostics
      (San Diego, CA), The Binding Site (Birmingham, England), and Wieslab (distributed
      by DiaSorin, Inc., Stillwater, MN). Percent agreement, sensitivity, and
      specificity were calculated for each EIA as compared to IFA. The results were as
      follows: Binding Site: 83.3, 100.0, and 72.0%; Wieslab: 95.2, 94.1, and 96.0%;
      INOVA: 96.2, 100.0, and 92.3%; and Scimedx: 81.0, 100.0, and 68.0%. We conclude
      that the INOVA and Wieslab GBM IgG EIAs compared well with the standard GBM IFA
      method using tissue from human kidney. The Scimedx and Binding Site EIAs had
      eight and seven false-positive results, respectively, when compared to GBM IFA
      using human kidney. The authors recommend conducting thorough evaluations of EIAs
      that screen for anti-GBM antibody before their implementation in the clinical
      laboratory. We also recommend confirming GBM EIA-positive sera by the standard
      IFA method using tissue from human kidney.

PMID- 11968052
TI  - Correlation of p21 gene codon 31 polymorphism and TNF-alpha gene polymorphism
      with nasopharyngeal carcinoma.
AB  - Background p21 (WAF1/CIP1) is a downstream protein from p53 and can arrest the
      cell cycle at the G1/S phase in response to signal from p53. The most frequently
      seen polymorphic site is at codon 31, where a base change from AGC to AGA causes
      an amino acid change from serine to arginine. Tumor necrosis factor-alpha (TNF
      alpha) is a cytokine that is secreted from macrophages, and is related to a
      sequence of events in the response to inflammation and cancer formation. The TNF
      alpha gene promoter -308 G/A polymorphism has been reported to be associated with
      some cancers. In this study, these polymorphisms were proposed to be a candidate
      genetic marker of nasopharyngeal carcinoma (NPC). The distribution was analyzed
      in 47 NPC patients and a control group of 119 healthy people. The association of
      the p21 codon 31 polymorphism with NPC was detected by polymerase chain reaction
      (PCR) and restriction analysis by Blp I endonuclease, and calculated by the chi
      square test. The TNF-alpha gene promoter -308 G/A polymorphism was identified by
      Nco I endonuclease. The distribution of the gene p21 codon 31 polymorphisms
      showed no significant difference between the two groups. The serine form of p21
      codon 31 was more prominent in smokers than nonsmokers among the NPC patients (P
      < 0.05). There was no significant difference in the distribution of TNF-alpha
      gene promoter -308 G/A polymorphism between control and cancer patients. The
      results indicate that the gene p21 codon 31 polymorphism and TNF-alpha promoter 
      308 polymorphism are not correlated with NPC. However, the difference between
      smokers and nonsmokers suggests that an environmental factor may be involved in
      association with the p21 gene in the formation of NPC.

PMID- 11968050
TI  - Hepatitis E antibody profiles in serum and urine.
AB  - The aim of this study was to evaluate anti-HEV antibody profiles in urine
      specimens in comparison to corresponding serum samples to assess the utility of
      urine as a clinical specimen. Paired serum and urine specimens from 71 hepatitis
      E patients, 33 non-E hepatitis patients, 63 patients with nonhepatic diseases,
      and 26 healthy individuals were tested by recombinant HEV protein (55 kD)-based
      indirect enzyme-linked immunosorbent assay (ELISA). Uronegativity for anti-HEV
      IgM was noted in 71 (100%) serologically confirmed patients with hepatitis E.
      Hepatitis E patients (10/10) showed urinary absence or very low levels of total
      IgM by capture ELISA, suggesting absence or low levels of filtration, and/or
      local synthesis, and/or transudation of IgM in urine during infection. When these
      patients were tested for total IgG and IgA, microquantities of immunoglobulins
      were noted in all urine samples (10/10 for each). However, the proportions of
      uropositivity for anti-HEV IgG and IgA in hepatitis E patients were low and
      indicated only 21.42% and 49.33% concordance with seropositivity, respectively.
      Control groups also showed low and variable uropositivity for anti-HEV IgG and
      IgA. Overall, HEV-specific antibodies exhibited by serum in recent and past
      infections were not found in urine. The study demonstrated the inadequacy of
      urine specimens for detection of hepatitis E antibodies.

PMID- 11968053
TI  - Comparative study of three different mycobacterial antigens with a novel
      lipopolysaccharide antigen for the serodiagnosis of tuberculosis.
AB  - Demonstration of Mycobacterium tuberculosis in a smear or culture is the most
      reliable method for diagnosing tuberculosis (TB). In the last 10 years, several
      enzyme-linked immunosorbent assays (ELISAs) based on mycobacterial antigens (such
      as antigen 60, 38 kDa antigen, and antigen Kp90) have been used for the rapid
      diagnosis of TB. In this study, we report the isolation of an immunodominant
      lipopolysaccharide (LPS) antigen from M. tuberculosis H(37)Rv, which can be used
      for the serodiagnosis of TB. The LPS antigen was compared with three commercially
      available mycobacterium-specific antigens for the detection of TB. The antigens
      were evaluated using serum samples obtained from 59 Indian patients (19 patients
      with active pulmonary TB, 20 with extrapulmonary TB, and 20 with nontuberculous
      pulmonary disease) and 20 healthy adults. Antigen 60 IgG (sensitivity 89%,
      specificity 97%) and LPS (sensitivity 84%, specificity 97%) were more sensitive
      and specific than 38 kDa antigen IgG (sensitivity 79%, specificity 97%) and Kp90
      IgA (sensitivity 82%, specificity 40%). These results indicate that the LPS
      antigen can be used as a sensitive tool for the serodiagnosis of TB and could be
      utilized to develop an ELISA for the screening of patients for TB.

PMID- 11968054
TI  - Follow-up of anti-Aspergillus IgG and IgA antibodies in bone marrow transplanted
      patients with invasive aspergillosis.
AB  - A total of 89 patients at risk for, or with invasive aspergillosis (IA) were
      recruited from bone marrow transplantation (BMT) units in two Lisbon hospitals,
      and followed for 2(1/2) years to monitor their immune response. Of these
      patients, six developed probable IA, from which five died. The presence of serum
      IgG or IgA antibodies against seven Aspergillus recombinant antigens was assessed
      in patients with IA, using an enzyme-linked immunosorbent assay (ELISA). In
      parallel, the serum levels of galactomannan (GM) were also monitored, using the
      Platelia Aspergillus kit (Sanofi Pasteur, Marnes-la-Coquette, France). Superoxide
      dismutase (Sod) and 94 kDa were the most immunogenic antigens for IgA, while the
      IgG pattern of recognition changed from patient to patient. From our results we
      conclude that although follow-up of antibodies against these antigens should not
      be used as a diagnostic method, patients with IA do produce an immune response
      that may influence disease outcome.

PMID- 11968055
TI  - Evaluation of a single-step multiplex RT-PCR for influenza virus type and subtype
      detection in respiratory samples.
AB  - A single-step multiplex reverse transcription-polymerase chain reaction (RT-PCR)
      for the simultaneous detection of influenza virus type and subtypes was evaluated
      for its use in clinical specimens. One part of each specimen was tested using an
      established standard culture and/or monoclonal antibody-based immunofluorescence
      assay method, and the other part was tested by the multiplex RT-PCR method for
      the presence or absence of the influenza virus, and its type and subtype. Sixty
      seven specimens were examined. The results revealed a strong agreement between
      the data obtained by the established method and those obtained by the multiplex
      RT-PCR.

PMID- 11968056
TI  - Mechanisms of apoptosis induced by purine nucleosides in astrocytes.
AB  - Astrocytes release adenine-based and guanine-based purines under physiological
      and, particularly, pathological conditions. Thus, the aim of this study was to
      determine if adenosine induced apoptosis in cultured rat astrocytes. Further, if
      guanosine, which increases the extracellular concentration of adenosine, also
      induced apoptosis determined using the TUNEL and Annexin V assays. Adenosine
      induced apoptosis in a concentration-dependent manner up to 100 microM. Inosine,
      hypoxanthine, guanine, and guanosine did not. Guanosine or adenosine (100 microM)
      added to the culture medium was metabolized, with 35% or 15%, respectively,
      remaining after 2-3 h. Guanosine evoked the extracellular accumulation of
      adenosine, and particularly of adenine-based nucleotides. Cotreatment with EHNA
      and guanosine increased the extracellular accumulation of adenosine and induced
      apoptosis. Inhibition of the nucleoside transporters using NBTI (100 microM) or
      propentophylline (100 microM) significantly decreased but did not abolish the
      apoptosis induced by guanosine + EHNA or adenosine + EHNA, respectively.
      Apoptosis produced by either guanosine + EHNA or adenosine + EHNA was unaffected
      by A(1) or A(2) adenosine receptor antagonists, but was significantly reduced by
      MRS 1523, a selective A(3) adenosine receptor antagonist. Adenosine + EHNA, not
      guanosine + EHNA, significantly increased the intracellular concentration of S
      adenosyl-L-homocysteine (SAH) and greatly reduced the ratio of S-adenosyl-L
      methioine to SAH, which is associated with apoptosis. These data demonstrate that
      adenosine mediates apoptosis of astrocytes both, via activation of A(3) adenosine
      receptors and by modulating SAH hydrolase activity. Guanosine induces apoptosis
      by accumulating extracellular adenosine, which then acts solely via A(3)
      adenosine receptors.

PMID- 11968057
TI  - Schwann cell caveolin-1 expression increases during myelination and decreases
      after axotomy.
AB  - The caveolins are a family of related proteins that form the structural framework
      of caveolae. They have been implicated in the regulation of signal transduction,
      cell cycle control, and cellular transport processes, particularly cholesterol
      trafficking. Caveolin-1 is expressed by a variety of cell types, including
      Schwann cells, although its expression is greatest in differentiated cell types,
      such as endothelial cells and adipocytes. In the present work, we characterize
      caveolin-1 expression both during rat sciatic nerve development and after
      axotomy. Schwann cells express little caveolin-1 on postnatal days 1 and 6. By
      P30, myelinating Schwann cells express caveolin-1, which is localized in the
      outer/abaxonal myelin membranes as well as intracellularly. After axotomy,
      Schwann cell caveolin-1 expression in the distal nerve stump decreases as Schwann
      cells revert to a premyelinating (p75-positive) phenotype; residual caveolin-1
      within the nerve largely localizes to myelin debris and infiltrating macrophages.
      We speculate that caveolin-1 plays a role in the biology of myelinating Schwann
      cells.

PMID- 11968059
TI  - Characterization of a synaptiform transmission between a neuron and a glial cell
      in the leech central nervous system.
AB  - The cross-talk between neurons and glial cells is receiving increased attention
      because of its potential role in information processing in nervous systems.
      Stimulation of a single identifiable neuron, the neurosecretory Leydig
      interneuron in segmental ganglia of the leech Hirudo medicinalis, which modulates
      specific behaviors in the leech, evokes membrane hyperpolarization directly in
      the giant glial cell (Schmidt and Deitmer. Eur J Neurosci 11:3125-3133, 1999). We
      have studied the neuron-to-glia signal transmission in the voltage-clamped giant
      glial cell to determine whether this interaction exhibits properties of a
      chemical synapse. The glial response had a mean latency of 4.9 s and was
      dependent on the action potential frequency; the glial cell responded to as few
      as five Leydig neuron action potentials in 50% of the trials. The glial current
      was sustained for minutes during repetitive Leydig neuron activity without any
      sign of desensitization. The current was sensitive to tetraethylammonium, and its
      reversal potential of -78 mV shifted with the external K+ concentration. The
      glial response increased with the duration of the neuronal action potentials and
      was sensitive to the external Ca2+/Mg2+ concentration ratio. The results suggest
      that Leydig neuron activity leads to a Ca2+-dependent release of transmitter from
      the neuronal dendrites, evoking an K+ outward current in the giant glial cell,
      implying a synapse-like transmission between a neuron and a glial cell.

PMID- 11968058
TI  - Effects of prolactin on intracellular calcium concentration and cell
      proliferation in human glioma cells.
AB  - Prolactin (PRL) has several physiological effects on peripheral tissues and the
      brain. This hormone acts via its membrane receptor (PRL-R) to induce cell
      differentiation or proliferation. Using reverse transcription-polymerase chain
      reaction (RT-PCR) combined with Southern blot analysis, we detected PRL-R
      transcripts in a human glioma cell line (U87-MG) and in primary cultured human
      glioblastoma cells. These transcripts were deleted or not in their extracellular
      domains. We examined the effects of PRL on intracellular free Ca2+ concentration
      ([Ca2+](i)) in these cells in order to improve our understanding of the PRL
      transduction mechanism, which is still poorly documented. [Ca2+](i) was measured
      by microspectrofluorimetry using indo-1 as the Ca2+ fluorescent probe.
      Spatiotemporal aspects of PRL-induced Ca2+ signals were investigated using high
      speed fluo-3 confocal imaging. We found that physiological concentrations (0.4-4
      nM) of PRL-stimulated Ca2+ entry and intracellular Ca2+ mobilization via a
      tyrosine kinase-dependent mechanism. The two types of Ca2+ responses observed
      were distinguishable by their kinetics: one showing a slow (type I) and the other
      a fast (type II) increase in [Ca2+](i). The amplitude of PRL-induced Ca2+
      increases may be sufficient to provoke several physiological responses, such as
      stimulating proliferation. Furthermore, PRL induced a dose-dependent increase in
      [3H]thymidine incorporation levels and in cellular growth and survival, detected
      by the MTT method. These data indicate that PRL induced mitogenesis of human
      glioma cells.

PMID- 11968060
TI  - Platelet-activating factor induces cell death in cultured astrocytes and
      oligodendrocytes: involvement of caspase-3.
AB  - The biologically active lipid metabolite, platelet-activating factor (PAF), is
      thought to contribute to inflammatory processes and tissue damage in a variety of
      central nervous system (CNS) injuries. In previous studies, we found that after
      contusion spinal cord injury, treatment with a PAF antagonist led to
      significantly increased white matter tissue sparing as well as decreased mRNA
      levels for pro-inflammatory cytokines. Some studies suggest that PAF can also
      have toxic effects on neurons in vitro. Few studies, however, have examined the
      effects of PAF on glial cells of the CNS. In the present study, the potential for
      PAF to act as a toxin to cultured astrocytes was examined. Also investigated were
      the effects of PAF on oligodendrocytes at two different stages of development.
      Treatment with 0.02-2 microM PAF for 72 h resulted in significant levels of cell
      death in both cell types (P < 0.05), an effect that was blocked by the PAF
      receptor antagonists, WEB 2170 and BN 52021. To investigate PAF-induced glial
      cell death further, we looked for activation of the enzyme, caspase-3, which can
      be indicative of apoptosis. Immunocytochemistry demonstrated that PAF at all
      concentrations caused activation of caspase-3 at 24, 48, and 72 h after treatment
      in both cell types. Caspase-3-dependent cell death was further confirmed using
      knockout mice (-/-) deficient in the caspase-3 gene. Toxicity was lost when
      astrocytes (-/-) were exposed to 0.02-2 microM PAF (P < 0.01). Oligodendrocytes (
      /-) were not susceptible to toxicity at 2 microM PAF (P < 0.001). The results
      demonstrate that the pro-inflammatory molecule, PAF, induces cell death in
      cultured CNS glial cells and that this effect is, in part, dependent on caspase-3
      activation.

PMID- 11968061
TI  - Carbohydrate source influences gelatinase production by mouse astrocytes in
      vitro.
AB  - Molecular mediators of ischemic brain injury include intercellular adhesion
      molecule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9), involved in the
      alteration of blood-brain barrier permeability and induced in astroglial cultures
      by tumor necrosis factor-alpha (TNF-alpha). Hyperglycemia is known to aggravate
      in vivo ischemic brain damage, while treatment with sorbitol shows benefit in
      reducing vasogenic brain edema. This study investigated whether a culture medium
      carbohydrate source could alter the astrocyte production of MMP-9 and ICAM-1 in
      vitro. The growth of astrocytes in 12.5 mM glucose, 25 mM glucose, or 25 mM
      sorbitol for 14 days did not alter cellular release of lactate dehydrogenase,
      uptake of Trypan blue, or surface expression of glial fibrillary acidic protein
      (GFAP). ICAM-1 levels were similar in astrocytes grown in glucose or sorbitol
      both under basal conditions and after TNF-alpha stimulation for 48 h. In
      contrast, levels of proMMP-9 released from astrocytes cultured for 14 days in 25
      mM sorbitol reached only 55-28% of those obtained from cultures in 25 mM glucose
      after stimulation with 1,000 U/ml (P = 0.05) or 5,000 U/ml (P < 0.025) TNF-alpha,
      respectively. Limiting the duration of pre-stimulation sorbitol exposure to 48 h
      resulted in lower proMMP-9 levels than in glucose cultures after 5,000, but not
      1,000, U/ml TNF-alpha, and differences were not significant when sorbitol
      exposure was further reduced to 24 h. Incubation in mixed glucose/sorbitol media
      did not affect the release of proMMP-9. These findings suggest that MMP-9
      production may be increased in astrocytes as a consequence of glucose metabolism,
      which can be avoided by growth in sorbitol alone.

PMID- 11968062
TI  - Distribution of two splice variants of the glutamate transporter GLT-1 in rat
      brain and pituitary.
AB  - We have performed immunocytochemistry on rat brains using a highly specific
      antiserum directed against the originally described form of the glutamate
      transporter GLT-1 (referred to hereafter as GLT-1alpha), and another against a C
      terminal splice variant of this protein, GLT-1B. Both forms of GLT-1 were
      abundant in rat brain, especially in regions such as the hippocampus and cerebral
      cortex, and macroscopic examination of sections suggested that both forms were
      generally regionally coexistent. However, disparities were evident; GLT-1alpha
      was present in the intermediate lobe of the pituitary gland, whereas GLT-1B was
      absent. Similar marked disparities were also noted in the external capsule, where
      GLT1A labeling was abundant but GLT-1B was only occasionally encountered.
      Conversely, GLT-1B was more extensively distributed, relative to GLT-1alpha, in
      areas such as the deep cerebellar nuclei. In most regions, such as the olfactory
      bulbs, both splice variants were present but differences were evident in their
      distribution. In cerebral cortex, patches were evident where GLT-1B was absent,
      whereas no such patches were evident for GLT-1alpha. At high resolution, other
      discrepancies were evident; double-labeling of areas such as hippocampus
      indicated that the two splice variants may either be differentially expressed by
      closely apposed glial elements or that the two splice variants may be
      differentially targeted to distinct membrane domains of individual glial cells.

PMID- 11968065
TI  - Yb(fod)3 in the spectroscopic determination of the configuration of chiral diols:
      a survey of the lanthanide diketonate method.
AB  - A modification of the diketonate method for the determination of the absolute
      configuration of chiral vicinal diols, first proposed by Nakanishi, is taken
      under object and tested with a set of aliphatic and aromatic substrates;
      Yb(fod)(3) (fod = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate) is
      employed as the chromophoric species. The replacement of dpm (dpm =
      dipivalomethanate) with fod ensures the formation of strong and stable signals in
      the UV region, whose signs are related to the configuration of the chelating
      molecule. The choice of ytterbium as the central cation introduces two major
      advantages: the electronic f-f transition of the rare-earth supplies a second
      spectral window in the near-IR, which is sensitive to the chemical environment
      around the atom. This allowed us to ascertain the number of different species
      present in solution and the observation of an induced CD also for strongly UV
      absorbing substrates. The pseudocontact shifts induced in the (1)H-NMR spectrum
      by the unpaired electron of the lanthanide ion provide valuable structural
      information on the adducts.

PMID- 11968066
TI  - Circular dichroism and absorption studies of (-)-2,2'-dimethyl-4,5-(1-naphthyl)
      1,3-dioxolane in terms of vibronic coupling theory.
AB  - The absorption and circular dichroism (CD) spectra of (-)-2,2'-dimethyl-4,5-(1
      naphthyl)-1,3-dioxolane (DND) were studied in the energy region 30,000 cm(-1) to
      50,000 cm(-1). The DND ketal is treated as a naphthalene dimer and its spectra
      are interpreted in terms of a vibronic dimer model which includes the (1)L(a) and
      (1)B(b) states of the naphthalene chromophore. To fix the most stable
      conformation of DND molecule, the MNDO/AM1, RHF/6-31G, and SVWN5, BPW91 methods
      are employed with 6-31G and 6-31G(d',p') basis sets. All the methods are shown to
      yield the DND geometry that is entirely consistent with the CD and absorption
      spectra studied.

PMID- 11968064
TI  - Electrophysiological characterization of retinal Muller glial cells from mouse
      during postnatal development: comparison with rabbit cells.
AB  - The electrophysiology of murine Muller cells, and of their precursors, during
      postnatal development was investigated by using the whole-cell patch-clamp
      technique. Membrane potential, membrane capacitance, and expression of voltage
      gated Na+ currents increased during the first 3 postnatal weeks. During the same
      period, the membrane resistance decreased due to an upregulation of both inward
      and outward K+ currents. Glutamate transporter-mediated currents increased during
      the first postnatal weeks, as well. In Muller (precursor) cells from rabbits,
      these transporter currents already achieved adult levels at postnatal day 6, the
      earliest stage studied. Together with the developmental time course of K+
      currents, this indicates a delay in the maturation of murine Muller cells, as
      compared with cells from rabbit.

PMID- 11968063
TI  - Functional expression of Kir 6.1/SUR1-K(ATP) channels in frog retinal Muller
      glial cells.
AB  - The retinae and brains of larval and adult amphibians survive long-lasting
      anoxia; this finding suggests the presence of functional K(ATP) channels. We have
      previously shown with immunocytochemistry studies that retinal glial (Muller)
      cells in adult frogs express the K(ATP) channel and receptor proteins, Kir6.1 and
      SUR1, while retinal neurons display Kir6.2 and SUR2A/B (Skatchkov et al., 2001a:
      NeuroReport 12:1437-1441; Eaton et al., in press: NeuroReport). Using both
      immunocytochemistry and electrophysiology, we demonstrate the expression of
      Kir6.1/SUR1 (K(ATP)) channels in adult frog and tadpole Muller cells. Using
      conditions favoring the activation of K(ATP) channels (i.e., ATP- and spermine
      free cytoplasm-dialyzing solution containing gluconate) in Muller cells isolated
      from both adult frogs and tadpoles, we demonstrate the following. First, using
      the patch-clamp technique in whole-cell recordings, tolbutamide, a blocker of
      K(ATP) channels, blocks nearly 100% of the transient and about 30% of the steady
      state inward currents and depolarizes the cell membrane by 5-12 mV. Second,
      inside-out membrane patches display a single-channel inward current induced by
      gluconate (40 mM) and blocked by ATP (200 microM) at the cytoplasmic side. The
      channels apparently show two sublevels (each of approximately 27-32 pS) with a
      total of 85-pS maximal conductance at -80 mV; the open probability follows a two
      exponential mechanism. Thus, functional K(ATP) channels, composed of Kir6.1/SUR1,
      are present in frog Muller cells and contribute a significant part to the whole
      cell K+ inward currents in the absence of ATP. Other inwardly rectifying
      channels, such as Kir4.1 or Kir2.1, may mediate the remaining currents. K(ATP)
      channels may help maintain glial cell functions during ATP deficiency.

PMID- 11968067
TI  - Generation of molecular chiral asymmetry through stirred crystallization.
AB  - In our earlier work we established that stirred crystallization of achiral
      compounds that crystallize in enantiomeric forms result in spontaneous chiral
      symmetry breaking. The asymmetry thus spontaneously generated is confined to the
      solid state. In this article, we present a case in which the crystal enantiomeric
      excess (CEE) can be converted to molecular enantiomeric excess (EE) through a
      solid state reaction which relates the enantiomeric form of the crystal to the
      enantiomeric form of the product. Such a process not only provides a means of
      detecting the CEE generated in stirred crystallization but it is also a means
      through which chiral asymmetry generated spontaneously is "propagated" to
      generate chiral compounds with enantiomeric excess.

PMID- 11968068
TI  - Ab initio prediction of optical rotation: comparison of density functional theory
      and Hartree-Fock methods for three 2,7,8-trioxabicyclo[3.2.1]octanes.
AB  - We report ab initio calculations of the frequency-dependent electric dipole
      magnetic dipole polarizabilities, beta(nu), at the sodium D line frequency and,
      thence, of the specific rotations, [alpha](D), of 2,7,8
      trioxabicyclo[3.2.1]octane, 1, and its 1-methyl derivative, 2, using the Density
      Functional Theory (DFT) and Hartree-Fock/Self-Consistent Field (HF/SCF)
      methodologies. Gauge-invariant (including) atomic orbitals (GIAOs) are used to
      ensure origin-independent [alpha](D) values. Using large basis sets which include
      diffuse functions DFT [alpha](D) values are in good agreement with experimental
      values (175.8 degrees and 139.2 degrees for (1S,5R)-1 and -2, respectively);
      errors are in the range 25-35 degrees. HF/SCF [alpha](D) values, in contrast, are
      much less accurate; errors are in the range 75-95 degrees. The use of small basis
      sets which do not include diffuse functions substantially lowers the accuracy of
      predicted [alpha](D) values, as does the use of the static limit approximation:
      beta(nu) approximately beta(o). The use of magnetic-field-independent atomic
      orbitals, FIAOs, instead of GIAOs, leads to origin-dependent, and therefore
      nonphysical, [alpha](D) values. We also report DFT calculations of [alpha](D) for
      the 1-phenyl derivative of 1, 3. DFT calculations find two stable conformations,
      differing in the orientation of the phenyl group, of very similar energy, and
      separated by low barriers. Values of [alpha](D) predicted using two different
      algorithms for averaging over phenyl group orientations are in good agreement
      with experiment. In principle, the absolute configuration (AC) of a chiral
      molecule can be assigned by comparison of the optical rotation predicted ab
      initio to the experimental value. Our results demonstrate the critical importance
      of the choice of ab initio methodology in obtaining reliable optical rotations
      and, hence, ACs, and show that, at the present time, DFT constitutes the method
      of choice.

PMID- 11968070
TI  - Stereospecific pH-dependent degradation kinetics of R- and S-naproxen-beta-l-O
      acyl-glucuronide.
AB  - The hydrolysis and acyl migration of biosynthetic S-naproxen-beta-l-O-acyl
      glucuronide (I) and R-naproxen-beta-l-O-acyl glucuronide (II) was followed by
      HPLC. Nine first-order kinetic rate constants for the hydrolysis and acyl
      migration between the beta-l-O-acyl glucuronide, its alpha/beta-2, alpha/beta-3-,
      alpha/beta-4-, and alpha-1-O-acyl isomers and naproxen aglycone were determined
      for I and II at pH 7.00, 7.40 and 8.00 at 37 degrees C by kinetic simulation. For
      I the 3-O-acyl isomer was the most stable isomer as the pseudo-equilibrium ratio
      for the major acyl-migrated isomers was 1:1.5:0.9 (2-O-acyl isomer:3-O-acyl
      isomer:4-O-acyl isomer). The 3- and 4-O-acyl isomers of II were equally stable as
      the pseudo-equilibrium ratio for the major acyl-migrated isomers was 1:1.4:1.4 (2
      O-acyl isomer:3-O-acyl isomer:4-O-acyl isomer). For both I and II, the pseudo
      equilibrium ratio between the major 2-O-acyl isomer and the minor alpha-l-O-acyl
      isomer was 10:1 (2-O-acyl isomer:alpha-l-O-acyl isomer). The pseudo-equilibrium
      found for the major acyl-migrated isomers of I and II in the present study
      corresponds with the pattern previously published for R- and S-ketoprofen-beta-l
      O-acyl glucuronide acyl-migrated isomers, suggesting that these findings may be
      general for acyl-migrated beta-l-O-acyl glucuronides of enantiomeric 2
      arylpropionic acids.

PMID- 11968069
TI  - Influence of input rate on the stereospecific and nonstereospecific first pass
      metabolism and pharmacokinetics of metoprolol extended release formulations.
AB  - The purpose of this study was to examine the influence of input rate on the
      stereoselective and nonstereoselective pharmacokinetics of metoprolol, alpha
      hydroxymetoprolol, and its acid metabolite. Extended release formulations (100
      mg) of metoprolol with varying release rates (e.g., slow (S), moderate (M), and
      fast (F)) and an oral solution (OS, 50 mg) were administered to normal, healthy
      extensive metabolizers. Serial blood samples were collected over 48 h, plasma was
      obtained, and subsequently analyzed by a validated HPLC method with fluorescence
      detection. The mean T(max) of metoprolol after the S, M, F (4.43, 4.00, 3.14 h,
      respectively) was found to be different ( P < 0.05) as compared to the OS (2.07
      h). The ratio of alpha-hydroxymetoprolol/metoprolol was higher for the OS (1.26)
      vs. the S, M, and F (1.02, 0.96, 0.99). The S/R enantiomer ratios of the
      concentration for metoprolol, ACMB, and alpha-hydroxmetoprolol were calculated at
      each time point and showed a significant difference ( P < 0.05) in the absorption
      phase (1-4 h) vs. terminal phase (8-16 h) for fast input (solution and fast
      extended release formulations). Based on these results, it would appear that
      input rate influences the pharmacokinetics of metoprolol, its metabolites, and
      their enantiomers.

PMID- 11968071
TI  - Preparative resolution of the enantiomers of tert-leucine derivatives by
      simulated moving bed chromatography.
AB  - The enantiomers of two different derivatives of tert-leucine were separated by
      continuous chromatography on chiral stationary phases applying the simulated
      moving bed technique. About 1 kg of racemic N-carbobenzoxy-tert-leucine was
      resolved on the cellulose-based phase Chiralcel OD using a mixture of
      heptane/ethanol and 0.1% of trifluoroacetic acid modifier as the mobile phase,
      while 520 g of the N-Boc-tert-leucine-benzylester was resolved on the amylose
      based phase Chiralpak AD with a mixture of heptane/2-propanol as the mobile
      phase. In both instances the corresponding enantiomers were obtained in high
      yield and high optical purity.

PMID- 11968072
TI  - Solubility, metastable zone width, and racemic characterization of propranolol
      hydrochloride.
AB  - Characterization of the racemic species, which can be a racemic compound, a
      racemic conglomerate, or a pseudoracemate (solid solution), is a prerequisite for
      the design of crystallization resolution processes. It is useful to determine the
      solid/liquid equilibrium solubility of the enantiomer mixtures for
      crystallization operation. For the beta-blocker drug propranolol hydrochloride,
      Gibbs free energy of formation of racemic compound and entropy of mixing of the
      (R)- and (S)- enantiomers in the liquid state for racemic conglomerate were
      calculated. The structural differences between (R, S)-propranolol hydrochloride
      and its (S)-enantiomer were further investigated by powder X-ray diffraction
      patterns, infrared spectra, and solid-state NMR spectra. The solubility and
      metastable zone width of (R, S)- propranolol hydrochloride in a mixed solvent of
      methanol and acetone were determined by cooling crystallization over the
      temperature range 3.5-42.5 degrees C. The ternary solubility diagram of (R)-, (S)
      propranolol hydrochloride was constructed using the same mixed solvent. The
      diagram will be useful as a guide for choosing crystallization operation
      conditions to produce pure enantiomers.

PMID- 11968073
TI  - Effective enzymatic resolution of rac-1-(3-trifluoromethylphenyl)propan-2-ol,
      precursor of fenfluramine.
AB  - Lipases from Candida antarctica and from Mucor miehei efficiently catalyze the
      enantioselective esterification of rac-1-(3-trifluoromethylphenyl)propan-2-ol.
      The obtained enantioforms are suitable to prepare both enantiomers of
      fenfluramine.

PMID- 11968074
TI  - NMR studies of chiral discrimination relevant to the enantioseparation of N
      acylarylalkylamines by an (R)-phenylglycinol-derived chiral selector.
AB  - Recently, it was reported that the chiral recognition ability of (R)-N-3,5
      dinitrobenzoyl phenylglycinol derivative was examined as a new HPLC chiral
      stationary phase (CSP 1) for the resolution of racemic N-acylnaphthylalkylamines.
      However, the mechanism of chiral discrimination on the CSP remained elusive until
      now. In this study, a spectroscopic investigation of the chiral discrimination
      mechanism of CSP 1 was undertaken using mixtures of (R)-N-3,5-dinitrobenzoyl
      phenylglycinol-derived chiral selector (2) and each of the enantiomers of N
      acylnaphthylalkylamines (3) by NMR study. First, the differences in free energy
      changes (DeltaDeltaG) upon diastereomeric complexation in solution between the
      complex of each isomer with chiral selector 2 by NMR titration were calculated.
      The values were then compared with those estimated by chiral HPLC. The chemical
      shift changes of each proton on the chiral selector and analytes were also
      checked and it was found that the chemical shift changes decreased continuously
      as the acyl group on analytes increased in length. This observation was
      consistent with the HPLC data. From these experimental results, the interaction
      mechanism of chiral discrimination between the chiral selector and the analytes
      is more precisely explained.

PMID- 11968075
TI  - Evaluation of reversible and irreversible models for the determination of the
      enantiomerization energy barrier for N-(p-methoxybenzyl)-1,3,2-benzodithiazol-1
      oxide by supercritical fluid chromatography.
AB  - It has been found that the interconversion of enantiomers on a chromatographic
      column during the separation process can be studied by the first-order kinetic
      equations derived both for reversible and irreversible reactions in a stationary
      system if the extent of interconversion is not too high. The equation derived for
      irreversible reactions gives, however, results also for higher degrees of
      enantiomerization while that derived for reversible interconversion failed. The
      irreversible equation was used to determine the enantiomerization barrier of N-(p
      methoxybenzyl)-l,3,2-benzodithiazol-l-oxide enantiomers by supercritical fluid
      chromatography. The racemate of N-(p-methoxybenzyl)-l,3,2-benzodithiazol-l-oxide
      was separated by supercritical fluid chromatography on the (R,R)-Whelk-Ol column
      with supercritical carbon dioxide containing 20% methanol as a mobile phase. Peak
      areas of enantiomers prior to and after the separation used for the calculation
      of the enantiomerization barrier were determined by computer-assisted peak
      deconvolution of peak clusters registered on chromatograms using commercial
      software.

PMID- 11968076
TI  - Synthesis of 11-cis-locked bicyclo[5.1.0]octanyl retinal and an enantioselective
      binding to bovine opsin.
AB  - Both enantiomers of 13-(E) and 13-(Z) isomers of 11-cis-locked
      bicyclo[5.1.0]octanyl retinal were prepared by an improved synthesis and
      incubated with bovine opsin. The synthesis also establishes the absolute
      configuration of the enantiomers. Only one of the enantiomers binds to opsin,
      thus showing the steric restrictions regarding the middle polyene moiety of the
      retinoid molecule; this is in sharp contrast to the known leniency of the ring
      moiety binding site of retinoids. However, although one enantiomer is
      incorporated into the pigment, the circular dichroic spectrum of the pigment
      incorporating the bound enantiomer yields only a very weak Cotton effect, showing
      that, once incorporated, the bicyclo[5.1.0]octanyl chromophore is flattened by
      the opsin binding site. The titled retinoid was synthesized for study of the
      absolute conformation of the retinal pigment in rhodopsin.

PMID- 11968077
TI  - Disposition of venlafaxine enantiomers in rats with hepatic encephalopathy after
      chronic drug treatment.
AB  - Portacaval shunted (PCS) rats, a model of hepatic encephalopathy, and control
      animals were administered racemic venlafaxine for 14 days (10 mg/kg). The levels
      of the S- and R-enantiomers and the S/R-enantiomer ratios of venlafaxine and its
      metabolites were assessed by an enantiomer-selective chromatographic assay in
      serum, brain parenchyma, and brain dialysate of both groups. Higher levels of the
      S- and R-enantiomers of venlafaxine were found in serum and brain of PCS vs.
      normal rats (median values of S- and R-venlafaxine in serum: 290 and 201 nM in
      PCS; 97 and 66 nM in normal rats; median values of S- and R-venlafaxine in
      cortex: 956 and 939 nM in PCS; 357 and 318 nM in normal rats). Interestingly,
      similar S/R-venlafaxine ratios were observed in PCS and normal rats both in serum
      (S/R = 1.4) and brain compartments (S/R = l.0-1.1). These findings may have
      clinical relevance for the safety of venlafaxine in chronic hepatic
      encephalopathy.

PMID- 11968078
TI  - Glutamate receptor ligands: synthesis, stereochemistry, and enantiopharmacology
      of methylated 2-aminoadipic acid analogs.
AB  - Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)
      Glu, 1], as well as absolute stereochemistry, are structural parameters of key
      importance for the pharmacological profile of (S)-Glu receptor ligands. We
      describe a series of methyl-substituted 2-aminoadipic acid (AA) analogs, and the
      synthesis, stereochemistry, and enantiopharmacology of 3-methyl-AA (4a-d), 4
      methyl-AA (5a-d), 5-methyl-AA (6a-d), and (E)-Delta(4)-5-methyl-AA (7a and 7b)
      are reported. The compounds were resolved using chiral HPLC and the
      configurational assignments of the enantiomers were based on X-ray
      crystallographic analyses, chemical correlation, and CD spectral analyses. The
      effects of the individual stereoisomers at ionotropic and metabotropic (S)-Glu
      receptors (iGluRs and mGluRs) were characterized. Compounds with S-configuration
      at the alpha-carbon generally showed mGluR2 agonist activity of similar or
      slightly lower potencies than (S)-AA [e.g., EC(50) = 76 microM for (2S,4S)-4
      methyl-AA (5a) as compared to EC(50) = 35 microM for (S)-AA]. The position of the
      methyl substituent had a profound effect on the observed pharmacology, whereas
      the absolute stereochemistry at the methylated carbon atom had a very limited
      effect on pharmacology. Structure-activity relationships at iGluRs in the rat
      cortical wedge preparation showed a complex pattern, some compounds being NMDA
      receptor agonists [e.g., EC(50) =110 microM for (2S,5RS)-5-methyl-AA (6a,b)] and
      some compounds showing NMDA receptor antagonist effects [e.g., IC(50) = 300
      microM for (2R,4S)-4-methyl-AA (5d)]. The two unsaturated analogs (S)- (7a) and
      (R)-(E)-Delta(4)-5-methyl-AA (7b) turned out to be a weak AMPA receptor agonist
      and a weak mixed NMDA/AMPA receptor antagonist, respectively.

PMID- 11968079
TI  - Pseudoachondroplasia and multiple epiphyseal dysplasia: mutation review,
      molecular interactions, and genotype to phenotype correlations.
AB  - Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) constitute a
      bone dysplasia family, which is both genetically and phenotypically
      heterogeneous. The disease spectrum ranges from mild MED, which manifests with
      pain and stiffness in the joints and delayed and irregular ossification of the
      epiphyses, to the more severe PSACH, which is characterized by marked short
      stature, deformity of the legs, and ligamentous laxity. PSACH is almost
      exclusively caused by mutations in cartilage oligomeric matrix protein (COMP)
      whereas various forms of MED are caused by mutations in the genes encoding COMP,
      type IX collagen (COL9A1, COL9A2, and COL9A3), matrilin-3 (MATN3), and solute
      carrier member 26, member 2 gene (SLC26A2). In this review we discuss specific
      disease-causing mutations and the clustering of these mutations in functionally
      and structurally important regions of the respective gene products, genotype to
      phenotype correlations, and the diagnostic relevance of mutation screening in
      these osteochondrodysplasias.

PMID- 11968080
TI  - Pyrosequencing: an accurate detection platform for single nucleotide
      polymorphisms.
AB  - Pyrosequencing, a non-electrophoretic method for DNA sequencing, is emerging as a
      popular platform for analysis of single nucleotide polymorphisms (SNPs). This
      technology has the advantage of accuracy, ease-of-use, and high flexibility for
      different applications. Here, we review the methodology and the use of this
      technique for SNP genotyping, SNP discovery, haplotyping, and allelic frequency
      studies. In addition, we describe new schemes for template preparation and
      multiplexing as an effort for cost reduction in large-scale studies.

PMID- 11968081
TI  - Mutations of RPGR in X-linked retinitis pigmentosa (RP3).
AB  - Mutations in RPGR, retinitis pigmentosa GTPase regulator, are associated with RP3
      type of X-linked retinitis pigmentosa, a severe, non-syndromic form of retinal
      degeneration. In the majority of subjects RPGR mutations are associated with a
      typical rod-cone degeneration, but in a small number, cone-rod dystrophy,
      deafness, and abnormalities in respiratory cilia have been noted. Alternative
      splicing of RPGR is complex in all species examined. In RP3 patients, mutations
      have been found in exons 1-14 and ORF15, thus delineating a transcript necessary
      for normal retinal function in humans. The great majority of mutations are
      predicted to result in premature termination of translation. These mutations are
      scattered over exons 1-14 and ORF15, while most missense mutations occur in a
      domain with homology to the protein RCC1, encoded by exons 1-10. Exon ORF15 is a
      "hot spot" for mutation, at least in the British population, in which it harbors
      80% of the mutations found within a sample of 47 X-linked retinitis pigmentosa
      patients. Most RPGR mutations are unique to single families, which makes it
      difficult to demonstrate phenotype-genotype correlations.

PMID- 11968082
TI  - GeneTests-GeneClinics: genetic testing information for a growing audience.
AB  - The development and usage of two companion NIH-funded genetic testing information
      databases, GeneTests (www.genetests.org) and GeneClinics (www.geneclinics.org),
      now merged into one web site, reflect the steadily increasing use of genetic
      testing and the expanding audience for genetic testing information. Established
      in 1993 as Helix, a genetics laboratory directory of approximately 110 listings,
      GeneTests has grown into a database of over 900 tests for inherited diseases, a
      directory of over 500 international laboratories, a directory of over 1,000 U.S.
      and international genetics clinics, and a resource for educational/teaching
      materials and reports of summary genetic test data. GeneClinics, founded in 1997
      as an expert-authored, peer-reviewed, disease-specific knowledge base relating
      genetic testing to patient care, has grown steadily, now containing over 130
      expert-authored, peer-reviewed full-text entries relating genetic testing
      information to diagnosis, management, and genetic counseling of specific
      inherited diseases. In spring 2001 the two databases were merged and in October
      2001 the two web sites were merged for the purpose of seamless navigation into
      the GeneTests-GeneClinics site (www.genetests.org or www.geneclinics.org); the
      GeneClinics knowledge base was renamed "GeneReviews" to avoid confusion with the
      U.S. and international clinic directories. As genetic testing has moved steadily
      out of research venues and into routine medical practice, the user audience for
      these databases has become international and expansive and includes healthcare
      providers, patients, educators, policy makers, and the media. The use of these
      combined resources has grown to approximately 3,200 visits/day.

PMID- 11968083
TI  - Screening E-cadherin in gastric cancer families reveals germline mutations only
      in hereditary diffuse gastric cancer kindred.
AB  - The International Gastric Cancer Linkage Consortium (IGCLC) predicted that up to
      25% of families fulfilling the criteria for hereditary diffuse gastric cancer
      (HDGC) would harbor CDH1 germline mutations. This was based on observations from
      the low number of diffuse gastric cancer families described at the time, and its
      validation would require analysis of larger numbers. Here we report the results
      of germline CDH1 mutation screening in 39 kindred with familial aggregation of
      gastric cancer, a subset of which fulfills the criteria defined by the IGCLC for
      HDGC. CDH1 germline mutations were detected in four of 11 (36.4%) HDGC families.
      No mutations were identified in 63.6% of HDGC families or in kindred with
      familial aggregation of gastric cancer not fulfilling criteria for HDGC. These
      results add support to the evidence that only HDGC families harbor germline
      mutations in CDH1 and that genes other than CDH1 remain to be identified.

PMID- 11968084
TI  - Novel germline CDH1 mutations in hereditary diffuse gastric cancer families.
AB  - Hereditary diffuse gastric cancer (HDGC) is a recently defined cancer syndrome
      caused by inactivating, heterozygous germline mutations in the gene for the cell
      to-cell adhesion protein E-cadherin (CDH1). Here, we describe the search for CDH1
      mutations in 10 newly identified gastric cancer families. Seven of 10 families
      met the clinical criteria for HDGC. Germline mutations were identified in four of
      these seven families and one family that was borderline for the clinical
      criteria. Of the mutations identified in the five new families, four were
      previously unreported and consisted of two frameshift and two donor splice site
      mutations. One splice site mutation occurred at the 100% conserved +1 position.
      The second splice site mutation occurred at the +5 position and was shown to lead
      to abnormal splicing. Additional CDH1 variants detected include the heterozygous 
      160 C-->A promoter polymorphism, which has previously been reported to be
      associated with decreased CDH1 transcription. We, however, found this
      polymorphism to be common in a control population, suggesting that a major role
      for this polymorphism in gastric cancer susceptibility is unlikely.

PMID- 11968085
TI  - Characterization of breakpoint sequences of five rearrangements in L1CAM and
      ABCD1 (ALD) genes.
AB  - Mutations in L1CAM are responsible for X-linked hydrocephalus, whereas those in
      the ALD gene (ABCD1) cause adrenoleukodystrophy. In both genes, most of the
      mutations reported so far are short-length mutations and only a few patients with
      larger rearrangements have been documented. We have characterized three
      intragenic deletions of the ALD gene at the molecular level and describe here the
      first two L1CAM rearrangements resulting in deletion of several exons in one case
      and about 50 kb, including the entire gene, in the second case. At both
      breakpoints of an ALD deletion, Alu repeats have been found and, additionally, a
      short Alu region of approximately 130 bp was inserted, suggesting that this
      rearrangement is the result of a more complex non-allelic homologous
      recombination event. Only one Alu element was present at the breakpoint of the
      second ALD rearrangement, including a 26-bp Alu core sequence that was suggested
      to be a recombinogenic hot spot. These data suggest the involvement of an Alu
      core sequence-stimulated non-homologous recombination as a possible cause for
      this rearrangement. Short direct repeats were identified at all putative
      mispaired sequences in the L1CAM breakpoints and at both breakpoints of the third
      ALD deletion characterized, suggesting non-homologous (illegitimate)
      recombination as the molecular mechanism by which these latter deletions
      occurred. In conclusion, our results indicate that highly repetitive elements as
      well as short direct repeats are frequently involved in the formation of ALD and
      L1CAM gene rearrangements.

PMID- 11968086
TI  - Sources of variability in genetic association studies: insights from the analysis
      of hepatic lipase (LIPC).
AB  - Genetic association studies have been widely used to identify loci that influence
      plasma lipoprotein concentrations, but few of the associations reported have
      proved consistently reproducible across different study populations. This lack of
      consistency is a widely recognized limitation of association studies, and is
      often ascribed to inadequate statistical power, population substructure, and
      population-specific linkage disequilibrium. However, few studies have assessed
      the causes of variability underlying a given genotype-phenotype association. We
      have examined two possible sources of variability in the association between the 
      514 polymorphism in hepatic lipase (LIPC) and plasma HDL-C concentrations. First,
      we compared the association between this polymorphism and hepatic lipase activity
      in four populations. A single copy of the -514C allele was associated with a 10
      mmol.hr(-1).l(-1) increase in hepatic lipase activity in white American and
      Turkish men but only approximately 5 mmol.hr(-1).l(-1) in Chinese and African
      American men. Second, we tested the effects of a stanozolol-induced increase in
      hepatic lipase activity on plasma HDL-C concentrations in men with normal (<
      150mg/dl) or elevated (150-300mg/dl) levels of plasma triglyceride. The increase
      in hepatic lipase activity was similar in the two groups, but the resulting
      decline in HDL-C levels was significantly greater in normolipidemic men. These
      data suggest that the effect of a polymorphism on gene expression can vary among
      individuals, and that the resulting phenotype may be further modified by
      interactions with other factors. Three novel LIPC polymorphisms were identified
      in the study (-1596insC, -2740A>G, and -2880G>C).

PMID- 11968087
TI  - Miniaturized sealed-tube allele-specific PCR.
AB  - DNA diagnostics has been progressively moving from expensive, low-throughput,
      multi-step methods towards inexpensive, robust, and high-throughput methods. Here
      we describe the further validation and refinement of a recently described novel
      genotyping method that has the latter characteristics. An evolved form of allele
      specific PCR, the method generates a fluorescent signal through the use of
      universal labeled primers, which can be quantified directly from microplates
      using standard plate readers. We have applied the method successfully to a test
      set of 12 novel single nucleotide polymorphisms (SNPs) on a panel of 47
      individuals using low reaction volumes. We demonstrate that the method is
      extremely accurate, robust, and can be optimized in a simple and predictable
      manner. By conducting the assay in closed-tube format, the potential for
      contamination is reduced to a minimum. By virtue of its simplicity, the method is
      versatile and cost-effective with potential for use in industrial-scale genetic
      studies or in the clinical diagnostic setting.

PMID- 11968088
TI  - Rapid genotyping of single nucleotide polymorphisms using novel minor groove
      binding DNA oligonucleotides (MGB probes).
AB  - Novel fluorescent oligonucleotides that contain a 3' minor groove binding group
      (MGB) hybridize to single-stranded targets with increased sequence-specificity
      compared to ordinary DNA probes. This reduces non-specific probe hybridization
      and results in low background fluorescence during the 5' nuclease PCR assay
      (TaqMan, Applied Biosystems, Foster City, CA). We developed a method for closed
      tube genotyping using two allele-specific MGB probes labeled with different
      fluorophores in one reaction. After PCR, tubes were transported to a fluorescence
      plate-reader for analysis of fluorescence. Common spreadsheet software was used
      for automated genotype assignment. As an example, DNA samples from 172
      hemochromatosis patients were selected and tested for molecular defects in the
      HFE gene, i.e., mutations in codon 63 and 282. Tight genotype clusters were
      observed for both codons and results with MGB probes were identical to
      conventional genotyping (PCR + restriction-fragment-length-polymorphism). We show
      that this fast and easy method can be used for large-scale (high-throughput)
      genetic studies but also for routine molecular diagnostics without post-PCR
      manipulation of amplicons or the need for real-time quantitative PCR machines.
      Hum Mutat 19:554-559, 2002.

PMID- 11968089
TI  - Low-density DNA microarrays are versatile tools to screen for known mutations in
      hypertrophic cardiomyopathy.
AB  - Familial hypertrophic cardiomyopathy (HCM or CMH) is a myocardial disorder caused
      by mutations that affect the contractile machinery of heart muscle cells. Genetic
      testing of HCM patients is hampered by the fact that mutations in at least eight
      different genes contribute to the disease. An affordable high-throughput mutation
      detection method is as yet not available. Since a significant number of mutations
      have been repeatedly found in unrelated families, we consider it feasible to pre
      screen patients for known mutations, before more laborious techniques capable of
      detecting new mutations are applied. Here we demonstrate that the principle of
      hybridization of DNA to oligonucleotide probes immobilized on chips (glass
      slides) can be applied for this purpose. We have developed a low-density
      oligonucleotide probe array capable of detecting 12 different heterozygous
      mutations (in four different genes), among them single- and double-base
      exchanges, a single nucleotide insertion, and a trinucleotide deletion. The assay
      is simple and may be amenable to automation. Detection is achieved with a CCD
      camera-based fluorescence biochip reader. The technique turned out to be robust:
      Variations in either the relative position of a mutation, or the amount and size
      of target-DNA were compatible with mutation detection. Mutations could even be
      detected in amplicons as long as 800 bp, allowing the screening of more than one
      exon in one amplicon. Our data suggest that the development of a chip that covers
      all or most of known HCM-associated mutations is feasible and useful.

PMID- 11968090
TI  - Crigler-Najjar syndrome type I in Tunisia may be associated with a founder effect
      related to the Q357R mutation within the UGT1 gene.

PMID- 11968091
TI  - GJB2 mutations in Iranians with autosomal recessive non-syndromic sensorineural
      hearing loss.
AB  - Hereditary hearing loss (HHL) is an extremely common disorder. About 70% of HHL
      is non-syndromic, with autosomal recessive forms accounting for approximately 85%
      of the genetic load. Although very heterogeneous, the most common cause of HHL in
      many different world populations is mutations of GJB2, a gene that encodes the
      gap junction protein connexin 26 (Cx26). This study investigates the contribution
      of GJB2 to the autosomal recessive non-syndromic deafness (ARNSD) load in the
      Iranian population. One hundred sixty eight persons from 83 families were
      studied. GJB2-related deafness was diagnosed in 9 families (4, 35delG
      homozygotes; 3, 35delG compound heterozygotes; 1, W24X homozygote; 1, non-35delG
      compound heterozygote). The carrier frequency of the 35delG allele in this
      population was approximately 1% (1/83). Because the relative frequency of Cx26
      mutations is much less than in the other populations, it is possible that
      mutations in other genes play a major role in ARNSD in Iran.

PMID- 11968092
TI  - Genetic variation screening and association studies of the adenylate cyclase
      activating polypeptide 1 (ADCYAP1) gene in patients with type 2 diabetes.
AB  - Adenylate cyclase activating polypeptide 1 (ADCYAP1) is a pancreatic neuropeptide
      and modulates glucose-stimulated insulin secretion. The ADCYAP1 gene is located
      on chromosome 18p11 linked to type 2 diabetes. To test whether it is a candidate
      gene for type 2 diabetes, screening of the gene in Finnish and Swedish type 2
      diabetic patients was done. Two novel SNPs, g.9863G>A (G54D) in exon 3 and
      g.12712C>G in the 3'-UTR of exon 5 of the ADCYAP1 gene (accession number X60435),
      were found. PCR-RFLP genotyping was then performed in a total of 253 type 2
      diabetic patients and 253 non-diabetic control subjects. Transmission
      disequilibrium test (TDT) was performed in 132 parent-offspring trios. The G
      allele frequencies of g.9863G>A (G54D) and g.12712C>G of the ADCYAP1 gene were
      higher in type 2 diabetic patients than in non-diabetic control subjects (21.0%
      vs 15.8%, P=0.04; 5.3% vs 3.0%, P=0.045). However, no significant differences in
      clinical variables was seen between the different genotype carriers, and also no
      transmission distortion of the G allele of SNP g.9863G>A (G54D) was observed in
      132 parent-offspring trios. The present study thus suggest that the variants in
      the ADCYAP1 gene may not be major influence of the susceptibility to type 2
      diabetes in Finnish and Swedish Caucasians.

PMID- 11968093
TI  - Four novel mutations of the PKD2 gene in Czech families with autosomal dominant
      polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a genetically
      heterogeneous disease caused by mutations in at least three different loci.
      Mutations in the PKD2 gene are responsible for approximately 15% of the cases of
      the disease. We have screened 14 Czech families for mutation in the PKD2 gene.
      Clear evidence against linkage to the PKD1 gene was established by CA-repeat
      markers in five families. The disease could be linked to both genes according to
      linkage analysis in nine families but we have chosen these families because of
      the mild clinical course. An affected member from each family was analyzed by
      heteroduplex analysis (HA) and single strand conformation polymorphism (SSCP) for
      all 15 coding regions. Samples exhibiting shifted bands on HA or SSCP gels were
      sequenced. We detected five mutations (four new, and one which was previously
      described) and two polymorphisms. The four new mutations include one insertion,
      one deletion, one substitution (leading to premature translation stop), one amino
      acid substitution. Our results confirm that different point or small changes
      distributed throughout the PKD2 gene without clustering are responsible for the
      disease.

PMID- 11968094
TI  - A HOXA13 allele with a missense mutation in the homeobox and a dinucleotide
      deletion in the promoter underlies Guttmacher syndrome.
AB  - Guttmacher syndrome, a dominantly inherited combination of distal limb and
      genital tract abnormalities, has several features in common with hand-foot
      genital syndrome (HFGS), including hypoplastic first digits and hypospadias. The
      presence of features not seen in HFGS, however, including postaxial polydactyly
      of the hands and uniphalangeal 2(nd) toes with absent nails, suggests that it
      represents a distinct entity. HFGS is caused by mutations in the HOXA13 gene. We
      have therefore re-investigated the original Guttmacher syndrome family, and have
      found that affected individuals are heterozygous for a novel missense mutation in
      the HOXA13 homeobox (c.1112A>T; homeodomain residue Q50L), which arose on an
      allele already carrying a novel 2-bp deletion (-78-79delGC) in the gene's highly
      conserved promoter region. This deletion produces no detectable abnormalities on
      its own, but may contribute to the phenotype in the affected individuals. The
      missense mutation, which alters a key residue in the recognition helix of the
      homeodomain, is likely to perturb HOXA13's DNA-binding properties, resulting in
      both a loss and a specific gain of function.

PMID- 11968119
TI  - Derivatization of small oligosaccharides prior to analysis by matrix-assisted
      laser desorption/ionization using glycidyltrimethylammonium chloride and Girard's
      reagent T.
AB  - In matrix-assisted laser desorption/ionization (MALDI) analyses of small
      oligosaccharides a very large increase in sensitivity (by a factor of 1000) may
      be obtained by introducing a quaternary ammonium center ('quaternization'). Such
      a quaternary ammonium center may be introduced into the saccharide by reaction
      with commercially available glycidyltrimethylammonium chloride (GTMA), or by
      using Girard's reagent T (Naven and Harvey, Rapid Commun. Mass Spectrom. 1996;
      10: 829). GTMA reacts with alcohol functionalities, whereas Girard's reagent T is
      specific for aldehyde and keto groups. Thus reducing saccharides can be
      derivatized by both GTMA and Girard's reagent T. For example, glucose or
      cellobiose having a stock concentration of 3 x 10(-5) M (5 microg/mL) produces no
      sugar-derived signals in conventional MALDI, but their quaternized derivatives,
      also at 3 x 10(-5) M, yield intense signals, with the matrix-derived signals only
      being weak. Similar results were obtained for glucosamine. Non-reducing
      saccharides as well as sugar alcohols can be derivatized using GTMA; thus,
      although sucrose, raffinose and sorbitol do not react with Girard's reagent T,
      they all produce intense signals after derivatization with GTMA. An example of
      the application of these derivatization reactions is provided by the analysis of
      oligosaccharides in beer.

PMID- 11968120
TI  - Highly robust stainless steel tips as microelectrospray emitters.
AB  - Tapered stainless steel spray tips for sheathless microelectrospray ionization
      (microESI) have been developed. The fabrication procedure for the tapered
      stainless steel tips was optimized using an electropolishing technique followed
      by removal of the burr. Using the tip as the microESI emitter, a stable ESI spray
      was obtained at a flow rate of 20 nL/min. The sensitivity of the microESI system
      was almost two orders greater than that of the conventional ion spray system. The
      tip was highly stable, and was successfully used for over 1000 h. Moreover, these
      stainless steel tips were suitable for use with sheathless capillary
      electrophoresis/mass spectrometry (CE/MS) and capillary liquid
      chromatography/mass spectrometry (LC/MS) for routine analysis in proteomic and
      pharmaceutical applications.

PMID- 11968121
TI  - Electrospray ionization mass spectrometric studies of phosphorus oxychloride
      directed synthesis of homo-oligopeptide ester libraries.
AB  - With the assistance of phosphorus oxychloride, alpha-amino acids were assembled
      into homo-peptides, which were analyzed by electrospray ionization mass
      spectrometry (ESI-MS) and multistage electrospray ionization mass spectrometry
      (ESI-MS/MS). On quenching with water or various alcohols, the reaction mixtures
      yielded the corresponding peptides or peptide esters, respectively. This paper
      reports a simple method to synthesize the homo-oligo-peptide-ester conjugated
      library by phosphorus oxychloride activation.

PMID- 11968122
TI  - Mass spectral studies on aryl-substituted N-carbamoyl/N-thiocarbamoyl narcotine
      and related compounds.
AB  - Positive ion mass spectral fragmentation of new N-carbamoyl/N-thiocarbamoyl
      derivatives of narcotine and compounds closely related to it are reported and
      discussed. The techniques used include electron impact (EI), fast-atom
      bombardment (FAB), matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) and electrospray ionization tandem mass spectrometry (ESI-MS/MS).
      Prominent peaks in the mass spectra of these compounds appear to involve C-C bond
      cleavage beta to the amine nitrogen with loss of the 4,5
      dimethoxy(1H)isobenzofuranone moiety from their molecular ions, along with
      another prominent peak at m/z 382. No molecular ion peaks of these compounds were
      recorded in EI, whereas intense [M + H]+ ion peaks were observed in FAB and ESI
      spectra. MALDI also yielded [M + H]+ ion peaks in good agreement with FAB and ESI
      studies.

PMID- 11968123
TI  - A rapid and precise method for sampling and determining the oxygen isotope ratio
      of atmospheric water vapor.
AB  - A quantitative method for cryogenically sampling atmospheric water vapor on the
      temporal scale of 10 to 15 min in the field or laboratory is described. The
      sample apparatus is lightweight, affordable, and easy to assemble. The method
      allows for H2O:CO2 equilibration within the same sampling tubes and hence
      increases turnaround time for delta18O analysis. Quantitative analysis in the
      laboratory showed recovery of a vaporized, known, 18O water standard to 0.2 per
      thousand precision.

PMID- 11968124
TI  - Determination of drug binding sites to proteins by electrospray ionisation mass
      spectrometry: the interaction of cisplatin with transferrin.
AB  - Cisplatin, cis-[PtCl2(NH3)2], is known to bind to human serum transferrin, but
      the binding site remains a matter of some debate. Electrospray ionisation mass
      spectrometry has been used to characterise the interaction of cisplatin with
      transferrin. The studies indicate that cisplatin initially docks with, and
      subsequently bonds covalently to, the hydroxyl functional group of threonine 457,
      with the loss of HCl affording a transferrin-O-PtCl(NH3)2 adduct.

PMID- 11968125
TI  - Electron capture dissociation of polypeptides using a 3 Tesla Fourier transform
      ion cyclotron resonance mass spectrometer.
AB  - Electron capture dissociation (ECD) of polypeptides has been demonstrated using a
      commercially available 3 Tesla Fourier transform ion cyclotron resonance (FTICR)
      instrument. A conventional rhenium filament, designed for high-energy electron
      impact ionisation, was used to effect ECD of substance P, bee venom melittin and
      bovine insulin, oxidised B chain. A retarding field analysis of the effective
      electron kinetic energy distribution entering the ICR cell suggests that one of
      the most important parameters governing ECD for this particular instrument is the
      need to employ low trapping plate voltages. This is shown to maximise the
      abundance of low-energy electrons. The demonstration of ECD at this relatively
      low magnetic field strength could offer the prospect of more routine ECD analysis
      for the wider research community, given the reduced cost of such magnets and (at
      least theoretically) the greater ease of electron/ion cloud overlap at lower
      field.

PMID- 11968126
TI  - Simultaneous determination of a drug candidate and its metabolite in rat plasma
      samples using ultrafast monolithic column high-performance liquid
      chromatography/tandem mass spectrometry.
AB  - An ultrafast bioanalytical method using monolithic column high-performance liquid
      chromatography/tandem mass spectrometry (HPLC/MS/MS) was evaluated for the
      simultaneous determination of a drug discovery compound and its metabolite in
      plasma. Baseline separation of the two compounds was achieved with run times of
      24 or 30 s under isocratic or gradient conditions, respectively. The monolithic
      column HPLC/MS/MS system offers shorter chromatographic run times by increasing
      flow rate without sacrificing separation power for the drug candidate and its
      biotransformation product (metabolite). In this work, the necessity for adequate
      chromatographic resolution was demonstrated because the quantitative
      determination of the drug-related metabolism product was otherwise hampered by
      interference from the dosed drug compound. The chromatographic performance of a
      monolithic silica rod column as a function of HPLC flow rates was investigated
      with a mixture of the drug component and its synthetic metabolite. The assay
      reliability of the monolithic column HPLC/MS/MS system was checked for matrix
      ionization suppression using the post-column infusion technique. The proposed
      methods were successfully applied to the analysis of study rat plasma samples for
      the simultaneous quantitation of both the dosed drug and its metabolite. The
      analytical results obtained by the proposed monolithic column methods and the
      'standard' silica particle-packed HPLC column method were in good agreement,
      within 10% error.

PMID- 11968127
TI  - Some aspects of matrix-assisted laser desorption/ionization analysis of
      hemoglobin from whole human blood.
AB  - Some aspects of the matrix-assisted laser desorption/ionization (MALDI) method in
      the analysis of hemoglobin from whole human blood are described. These aspects
      are: sensitivity of this method, fragmentation of hemoglobin ions, and influence
      of some impurities (sodium chloride NaCl, sodium sulfate Na2SO4, and potassium
      ferrocyanide K4Fe(CN)6) on the detection process. As a matrix, alpha-cyano-4
      hydroxycinnamic acid (CCA) was used. The estimated maximum concentrations of
      tested salts for which no hemoglobin signal was observed were determined.

PMID- 11968128
TI  - Using a high-resolution magnetic sector mass spectrometer for fast analysis of
      transient reaction processes in automotive catalytic converters.
AB  - A high-resolution magnetic sector mass spectrometer has been developed and used
      for transient kinetic measurements on reactions that are important for automotive
      exhaust gas catalysis. This instrument allows separation of the isobaric masses
      of CO and N2 as well as CO2 and N2O, which are separately monitored in time at a
      sampling rate of 48 Hz. The time resolution is sufficient to determine individual
      kinetic rate parameters for reactions under transient conditions. A description
      of the experimental set-up as well as the software used is given. The results are
      illustrated by the catalytic reduction of NO by CO. To the best knowledge of the
      authors, this is the first application of a magnetic sector mass spectrometer for
      kinetic research under dynamic operation conditions.

PMID- 11968129
TI  - Simultaneous separation of 17 inorganic and organic arsenic compounds in marine
      biota by means of high-performance liquid chromatography/inductively coupled
      plasma mass spectrometry.
AB  - A method using high-performance liquid chromatography/inductively coupled plasma
      mass spectrometry (HPLC/ICP-MS) has been developed to determine inorganic arsenic
      (arsenite, arsenate) along with organic arsenic compounds (monomethylarsonic
      acid, dimethylarsinic acid, arsenobetaine, arsenocholine, trimethylarsine oxide,
      tetramethylarsonium ion and several arsenosugars) in fish, mussel, oyster and
      marine algae samples. The species were extracted by means of a methanol/water
      mixture and a dispersion unit in 2 min, with extraction efficiencies ranging from
      83 to 107% in the different organisms. Up to 17 different species were determined
      within 15 min on an anion-exchange column, using a nitric acid gradient and an
      ion-pairing reagent. As all species are shown in one chromatogram, a clear
      overview of arsenic distribution patterns in different marine organisms is given.
      Arsenobetaine is the major compound in marine animals whereas arsenosugars and
      arsenate are dominant in marine algae. The method was validated with CRM DORM-2
      (dogfish muscle). Concentrations were within the certified limits and low
      detection limits of 8 ng g(-1) (arsenite) to 50 ng g(-1) (arsenate) were
      obtained.

PMID- 11968130
TI  - A rapid and sensitive liquid chromatography/negative ion tandem mass spectrometry
      method for the determination of an indolocarbazole in human plasma using 96-well
      diatomaceous earth plates for solid-liquid extraction [correction of using
      internal standard (IS) 96-well diatomaceous earth plates for solid-liquid
      extraction].
AB  - A sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for
      the quantitation of a novel topoisomerase I inhibitor (indolocarbazole derivative
      I) in human plasma was developed to support clinical studies. Drug and internal
      standard were isolated from plasma by solid-liquid extraction using 96-well
      diatomaceous earth plates. Various extraction solvents were evaluated for
      extraction of I and 9% isopropyl alcohol (IPA) in methyl-tert-butyl ether (MtBE)
      was chosen as the optimal extraction solvent. The sensitivity of this LC/MS/MS
      method is 10x higher in negative ion mode using alkaline conditions than in
      positive ion mode using a wide range of pH's. A mobile phase with 2 mM ammonium
      hydroxide enhanced the sensitivity in negative ion mode over other volatile
      bases. The calibration curve for compound I is linear over the range 0.05-200
      ng/mL in plasma and the lower limit of quantification (LLOQ) of the assay is 0.05
      ng/mL, when 0.25 mL of plasma is processed. The method was fully validated and
      successfully applied to plasma samples from clinical studies. Performing
      chromatography at high pH, for enhanced negative ion sensitivity, eliminates the
      need for post-column addition of base. Furthermore, the 96-well diatomaceous
      earth plate extraction offers the following advantages over liquid-liquid
      extraction (LLE) or solid-phase extraction (SPE): clean sample extracts with
      reduced sample preparation time; increased sample throughput; no conditioning or
      washing steps; and a neutral eluate applicable to acid/base labile compounds.

PMID- 11968131
TI  - Characterization and sequence confirmation of unnatural amino acid containing
      peptide libraries using electrospray ionization mass spectrometry.
AB  - The content of 24 12-membered heptapeptide libraries was investigated using
      capillary liquid chromatography coupled with an electrospray ionization
      quadrupole orthogonal acceleration time-of-flight mass spectrometer. Adjustment
      of the chromatographic parameters led to the separation of most of the
      components. Extraction of the [M + 2H]2+ ions allowed us to demonstrate the
      presence of all expected species in the library and to evaluate their relative
      abundance in the mixture. Rapid sequence confirmation was achieved by subtraction
      of product ion spectra, a way to eliminate common ions and to simplify the
      spectra for interpretation. This technique can also easily be applied to other
      libraries consisting of components with a common core.

PMID- 11968132
TI  - Liquid chromatography and electron-capture dissociation in Fourier transform ion
      cyclotron resonance mass spectrometry.
AB  - Liquid separation methods in combination with electrospray mass spectrometry as
      well as the recently introduced fragmentation method electron capture
      dissociation (ECD) have become powerful tools in proteomics research. This paper
      presents the results of the first successful attempts to combine liquid
      chromatography (LC) and Fourier transform ion cyclotron resonance mass
      spectrometry (FTICRMS) with ECD in the analysis of a mixture of standard peptides
      and of a bovine serum albumin tryptic digest. A novel electron injection system
      provided conditions for ECD sufficient to yield extensive sequence information
      for the most abundant peptides in the mixtures on the time-scale of the
      chromatographic separation. The results suggest that LC/ECD-FTICRMS can be
      employed in the characterization of peptides in enzymatic digests of proteins or
      protein mixtures and identify and localize posttranslational modifications.

PMID- 11968133
TI  - Micro-high-performance liquid chromatography/Fourier transform mass spectrometry
      with electron-capture dissociation for the analysis of protein enzymatic digests.
AB  - Electron-capture dissociation (ECD) Fourier transform mass spectrometry (FTMS)
      employed to generate comprehensive sequence information for the chromatographic
      analysis of enzymatic protein digests is described. A pepsin digest of cytochrome
      c was separated by reversed-phase micro-high-performance liquid chromatography
      (microHPLC) and ionized 'on-line' by electrospray ionization (ESI). The ions thus
      formed were transferred to and trapped in the FTMS analyzer cell. Typically, no
      precursor ion isolation was performed. The trapped ions were subjected to a pulse
      of electrons to induce fragmentation. Mass spectra were acquired continuously to
      produce a three-dimensional LC/MS data set. The spectra were dominated by c and,
      to a lesser degree, z ions, which provided near complete sequence coverage.
      External calibration provided good mass accuracy and resolution, typical of FTMS.
      Thus microHPLC/ECD - FTMS is shown to be a highly informative method for the
      analysis of enzymatic protein digests.

PMID- 11968134
TI  - Identification of phosphopeptides by chemical modification with an isotopic tag
      and ion trap mass spectrometry.

PMID- 11968135
TI  - Senile plaques do not induce susceptibility effects in T2*-weighted MR
      microscopic images.
AB  - Senile plaques are the hallmarks of Alzheimer's disease. They typically range
      from 16 to 150 microm in size with most less than 25 microm. Mechanisms by which
      they might affect MR contrast and thus be made visible in this imaging modality
      are still unknown. Plausibility studies suggested that they might have a
      different magnetic susceptibility than surrounding tissue. A large difference
      would cause the plaque and a relatively large volume of adjacent tissue to be
      hypo-intense in T2*-weighted MRI scans, thus causing them to appear larger than
      their actual sizes and perhaps visible even when their size is below the nominal
      resolution limit of the imaging experiment. To evaluate this hypothesis, formalin
      fixed superior temporal gyrus samples obtained from two Alzheimer's disease and
      two control subjects were imaged using magnetic resonance microscopy at 11.7 T.
      Three dimensional T2*-weighted gradient echo images were recorded with an
      isotropic resolution of 23.4 microm. The imaging protocol was especially
      sensitive to susceptibility effects. Samples were then stained for amyloid and/or
      iron deposits. Hypo- and hyper-intense structures were clearly visible in MR
      images from all samples. Hyper-intense structures reflected fixative penetration
      within the vascular system. Almost all the hypo-intense structures were blood
      vessels. Their hypo-intense profile was probably caused by iron deposits
      associated with the cell aggregates that they contained. Only one hypo-intense
      spot could be matched with a plaque and this was one of the largest plaques in
      our samples. The remainder of the several hundred plaques were not visible in MR
      images. In histological slices the senile plaques were often larger than small
      blood vessels that were visible in the MR images. This suggests that
      susceptibility effects are not associated with senile plaques and do not provide
      a mechanism to differentiate them from surrounding tissue.

PMID- 11968136
TI  - Monitoring acute inflammatory processes in mouse muscle by MR imaging and
      spectroscopy: a comparison with pathological results.
AB  - We have studied an animal model of acute local inflammation in muscle induced by
      Aspergillus fumigatus by using magnetic resonance imaging (MRI) and magnetic
      resonance spectroscopy (MRS). We have compared our data to those found using
      histopathology and segmentation maps obtained by the mathematical processing of
      three-dimensional T2-weighted MRI data via a neural network. The MRI patterns
      agreed satisfactorily with the clinical and biological evidence of the phases of
      acute local infection and its evolution towards chronicity. The MRS results show
      a statistically significant increase in inorganic phosphate and a significant
      decrease in phosphocreatine levels in the inflamed region. Image segmentation
      made with a self-organizing, neural-network map yielded a set of ordered
      representatives that remained constant for all animals during the inflammatory
      process, allowing a non-invasive, three-dimensional identification and
      quantification of the inflamed infected regions by MRI.

PMID- 11968137
TI  - Relaxation times of choline, creatine and N-acetyl aspartate in human cerebral
      white matter at 1.5 T.
AB  - Several studies have investigated the T1 and T2 relaxation time of choline,
      creatine and N-acetyl aspartate in cerebral white matter in normal human
      subjects. However, these studies demonstrate a large variation in T1 and T2
      values. In the present study, relaxation times of choline, creatine and N-acetyl
      aspartate were determined in cerebral white matter in 15 control subjects (age 21
      +/- 2 y, mean +/- SD) at 1.5 T. Using PRESS, seven or eight data points were
      obtained to fit the T1 and T2 relaxation curves to, respectively. The mean voxel
      size was 14 cm3. The T1 relaxation times of choline, creatine and N-acetyl
      aspartate were 1091 +/- 132 (mean +/- SD), 1363 +/- 137 and 1276 +/- 132 ms. The
      T2 relaxation times were 352 +/- 52, 219 +/- 29 and 336 +/- 46 ms, respectively.

PMID- 11968138
TI  - Non-invasive measurements of myocardial carbon metabolism using in vivo 13C NMR
      spectroscopy.
AB  - Despite their prime role in maintaining contractile performance, myocardial
      substrate uptake, substrate preference and metabolism are difficult to assess non
      invasively. The objective of the present work was to extend the scope of cardiac
      13C nuclear magnetic resonance (NMR) spectroscopy to the in vivo situation
      ('closed-chest model') and to quantitatively appraise myocardial metabolism in
      vivo. For this purpose, overnight-fasted Sprague-Dawley rats received intravenous
      infusions of non-radioactive 13C-labeled glucose, 3-hydroxybutyrate, and acetate
      as markers for glycolysis, metabolism of ketone bodies and direct incorporation
      into tricarboxylic acid (TCA) cycle, respectively. In vivo 13C NMR spectra (at 7
      T) were acquired from the myocardium with a time resolution of 6 min. At the end
      of the infusion experiments, tissue extracts were prepared and further analyzed
      by high-resolution 13C NMR spectroscopy in order to corroborate the findings
      obtained in vivo. Accordingly, 3-hydroxybutyrate and acetate were rapidly
      extracted by the myocardium and supplied 42 +/- 6 and 53 +/- 9% of the acetyl-CoA
      for TCA cycle operation, whereas glucose, although also well extracted, did not
      contribute to myocardial oxidative metabolism. Myocardial TCA cycle turnover
      (V(TCA)) in vivo was estimated at 1.34 +/- 0.07 micromol/min/g wet weight,
      myocardial oxygen consumption (MVO2) at 2.95 +/- 0.16 micromol/min/g wet weight,
      exchange rate between alpha-ketoglutarate and glutamate (V(x)) at 1.22 +/- 0.08
      micromol/min/g wet weight and rate of glutamine synthesis (V(gln)) at 0.14 +/-
      0.02 micromol/min/g wet weight. The substantial synthesis of myocardial glutamine
      is in contrast to experiments with isolated and saline perfused hearts. In
      conclusion, it is demonstrated that 13C NMR spectroscopy of the heart in intact
      rats is feasible and provides new quantitative insight into myocardial substrate
      uptake, preference and metabolism in vivo.

PMID- 11968139
TI  - Combined diffusion weighting and CSF suppression in functional MRI.
AB  - In this study, EPI pulse sequences with diffusion weighting for reduction of
      contributions from large vessels and inversion pulses in order to minimize the
      effects of CSF pulsations and CSF partial volume effects were developed for BOLD
      contrast investigations in functional MR imaging. One inversion recovery echo
      planar imaging (IR-EPI) pulse sequence and one IR-EPI with additional diffusion
      weighting (DW-IR-EPI) were developed and compared to a standard gradient-echo EPI
      sequence in a cortical stimulation experiment in nine healthy volunteers.
      Stimulation of motor cortex was performed using a semi-complex finger-tapping
      paradigm in seven periods of alternating rest and stimulation. Comparison between
      the three pulse sequences was made by measuring the activated volume in each
      subject, as well as by calculating the relative signal increase during
      stimulation. Due to different baseline signal-to-noise levels in the images
      generated by the three pulse sequences, artificial noise was added so that the
      comparative investigation could be performed independently of the noise level.
      The activated volume was 128 +/- 73 pixels (mean +/- SD) using the standard EPI
      pulse sequence, 31 +/- 12 pixels using IR-EPI and 15 +/- 13 pixels when DW-IR-EPI
      was employed. The relative signal increase was 5.7 +/- 1.1% using standard EPI,
      11.5 +/- 3.1% using IR-EPI and 9.9 +/- 2.4% using DW-IR-EPI. The activated volume
      obtained with the addition of extra noise, i.e. at equal S/N, was 70 +/- 50
      pixels using the standard EPI, and when using IR-EPI, the activated volume was 28
      +/- 13 pixels. At equal S/N, the signal increase was 7.3 +/- 1.4% using standard
      EPI and 12.0 +/- 3.6% using IR-EPI. In BOLD contrast imaging, a combination of
      diffusion weighting and inversion recovery appeared to reduce false activation
      caused by CSF pulsation and blood flow in large vessels.

PMID- 11968141
TI  - Current awareness in NMR in biomedicine.

PMID- 11968140
TI  - 1H NMR spectroscopy as a tool to evaluate key metabolic functions of primary
      porcine hepatocytes after cryopreservation.
AB  - Proton NMR spectroscopy of biological fluids has produced interesting results
      lately. We used the technique to investigate the effects of cryopreservation on
      primary porcine hepatocytes as successful cryopreservation of primary porcine
      hepatocytes is of importance to the development of bioartificial liver support
      systems. After isolation 10(8) hepatocytes were cryopreserved for 1 week in
      Williams E/10% DMSO, either by quick freezing (-5 to -30 degrees C/min), slow
      freezing (-0.3 to -3 degrees C/min) or stepwise freezing protocols on cell
      suspensions and confluent cell plates. Plating efficiency was assessed by
      percentage LDH release. Metabolic functions of cryopreserved hepatocytes at 24 h
      post-thawing were compared with those of fresh hepatocyte cultures at 48 h. 1H
      nuclear magnetic resonance spectroscopy of the culture medium post-incubation,
      using the presaturation technique, assessed the following: glucose metabolism,
      transamination and glutamine synthesis and succinate synthesis. Freshly isolated
      cells had a viability of 82 +/- 4.3% and a plating efficiency of 87 +/- 3.8%. All
      cryopreservation protocols resulted in significantly reduced viability and
      plating efficiency. No significant differences were observed between different
      cryopreservation media or protocols. When comparing cryopreserved with freshly
      isolated cells, we observed that metabolism of acetyl-CoA precursors was
      significantly impaired in cryopreserved cells. Lactate and pyruvate production
      was also significantly less, although glucose consumption was similar. No
      differences were observed in gluconeogenic amino acid metabolism, transamination
      and urea synthesis. 1H NMR spectroscopy can be used to provide information about
      metabolic activity and functions of cultured primary cells.

PMID- 11968142
TI  - [Proceedings of the IV National Population Workshop: Ontogenesis and Population.
      Moscow, May 18-19, 2001].

PMID- 11968143
TI  - [21st century: crisis of medicine?].

PMID- 11968144
TI  - Gingival masks: a simple prosthesis to improve the appearance of teeth.

PMID- 11968145
TI  - Diabetes and periodontal disease: two sides of a coin.
AB  - Diabetes and periodontal disease are two seemingly unrelated disorders whose
      complex interrelationship is only now being clarified. How does diabetes, a
      metabolic disease, affect the periodontium? Perhaps even more interesting for the
      diabetic patient: How does periodontal disease, a bacterial infection that
      results in inflammation and tissue destruction in the oral cavity, impact the
      metabolic control of diabetes? Evidence clearly supports diabetes as a risk
      factor for periodontal disease. The mechanisms by which diabetes adversely
      influences the periodontium are in many ways similar to the mechanisms
      responsible for the classic complications of diabetes. In recent years, research
      has demonstrated that the relationship between periodontal disease and diabetes
      is more complex than previously realized. Not only does diabetes affect the
      periodontium, but periodontal infection can adversely impact glycemic control in
      diabetes. Periodontal treatment that decreases the bacterial challenge and the
      resulting inflammatory periodontal destruction can improve glycemia in some
      diabetic patients. These research findings are of importance to diabetic patients
      and their health care providers, because the findings support the need for
      examination, diagnosis, treatment, and prevention of periodontal infection.

PMID- 11968146
TI  - Dental water lines.

PMID- 11968147
TI  - An evaluation of the effectiveness of two canal lubricants in removing smear
      layer.
AB  - This study used scanning electron microscopy to compare the effectiveness of two
      new canal lubricants in conjunction with sodium hypochlorite irrigation in
      removing smear layer. Both lubricants completely removed the smear layer in the
      coronal and middle thirds of the root canals, but only partially removed the
      smear layer in the apical thirds. An explanation of the findings is presented and
      the clinical significance of smear layer is discussed.

PMID- 11968148
TI  - Advances in restorative core materials.
AB  - The use of core build-up materials is likely to increase in coming years. The
      ease of use of direct materials, such as amalgam and composite-based core
      materials, will most certainly dominate product selection. The historic standard
      of the custom cast post-and-core technique is decreasing in the private practice
      of dentistry. Providing the foundation for a restoration that will endure the
      masticatory stresses that occur in the oral cavity for prolonged periods is a
      goal all conscientious dentists are pursuing. Only with a thorough understanding
      of the individual patient's oral conditions can an accurate assessment be made
      regarding material selection. Minimizing the risks associated with failure should
      include a knowledge of the material's properties, the forces that the core build
      up must withstand, the occlusal scheme of the patient, and the final type of
      restoration or prosthesis to be fabricated. An extreme amount of professional
      judgement and past experience must be used in the absence of sound scientific
      validation. Unfortunately, little sound research, especially clinical research,
      exists to assist dentists in this area. New clinical studies in this area would
      be of tremendous benefit to the practicing dentists and would benefit the general
      public greatly.

PMID- 11968149
TI  - The evolution of instrumentation and obturation leading to a simplified approach.
AB  - The evolution of endodontic treatments has included the introduction of rotary
      crown-down nickel-titanium instrumentation and the use of thermoplasticized gutta
      percha to obturate canals. Although these techniques have provided dentists with
      solutions to problems encountered with earlier generation endodontic procedures,
      they have also presented deficiencies that are now receiving some critical
      review. As a result, a systematic technique has been developed that provides a
      simplified approach for root canal instrumentation and predictable obturation.
      This article reviews the aspects of earlier endodontic techniques and provides
      the step-by-step clinical protocol involved with simplified endodontic
      techniques.

PMID- 11968150
TI  - Medium-viscosity polyether impression material: a case report.
AB  - Polyethers are elastomeric materials commonly used for making precision
      impressions. They are hydrophilic, which facilitates the contact of the unset
      material with the intraoral tissue and the wetting of the impression by cast
      materials. The final hardness of this new impression material is reduced in an
      attempt to overcome rigidity of the set impression. A case is described involving
      the restoration of a fractured maxillary premolar and a single-phase impression
      technique using the new polyether impression material.

PMID- 11968152
TI  - Community networks. St. Paul's Caritas Health Ministry, Flushing, NY.

PMID- 11968151
TI  - Conflicting results on ginkgo research.

PMID- 11968153
TI  - Reflection on mission.

PMID- 11968154
TI  - Pharmacokinetics of rhuMAb CD18, a recombinant humanised monoclonal antibody
      fragment to CD18, in normal healthy human volunteers.
AB  - BACKGROUND AND OBJECTIVES: Leucocyte 2 integrin adhesion receptors are
      hypothesised as a therapeutic target to modify immune responses to ischaemia
      reperfusion injury that may be detrimental to recovery in a variety of disease
      states. Two phase I studies were designed to evaluate the pharmacokinetics,
      immunogenicity and safety of rhuMAb CD18, a humanised monoclonal antibody
      F(ab')(2) fragment to the CD18 receptor, in normal healthy human volunteers.
      STUDY DESIGN AND METHODS: The first study evaluated six escalating doses of
      rhuMAb CD18 (0.06, 0.12, 0.25, 0.5, 1.0, 2.0 mg/kg) in 36 subjects given two
      intravenous (IV) bolus injections 12 hours apart. In the second study, 16
      subjects received IV doses of 1.0 and 2.0 mg/kg as a single dose or as two doses
      given 12 hours apart. Study endpoints were rhuMAb CD18 serum pharmacokinetics,
      change in white blood cell (WBC) count, and safety and tolerability. The two
      studies enrolled a total of 53 subjects. RESULTS: Serum concentration-time
      profiles demonstrated a monophasic decline and were best characterised by a one
      compartment pharmacokinetic model. At the doses administered, the volume of
      distribution approximated the serum volume (range of means: 42 to 58 ml/kg). The
      serum clearance decreased with increasing dose until becoming consistent at doses
      of 0.5 to 2.0 mg/kg (range of means: 3.1 to 5.0 ml/h/kg). At doses of 0.5 to 2.0
      mg/kg, the mean elimination half-life ranged from 7.0 to 9.6 hours. WBC counts
      increased at doses of above 0.06 mg/kg, returning to within 20% of predose values
      by day 7. Antibodies to rhuMAb CD18 were not detected at day 28. Mild-to-moderate
      adverse events were observed in both the placebo and treated groups, and were
      limited to flu-like symptoms. One subject experienced a serious adverse event
      (febrile reaction) and recovered with minimal intervention. There was no evidence
      of an increase in infection in subjects who received rhuMAb CD18. CONCLUSIONS:
      Upon IV bolus administration, rhuMAb CD18 serum concentration-time data fit a one
      compartment pharmacokinetic model. At doses of 0.5 to 2.0 mg/kg, the
      pharmacokinetics were linear and the half-life ranged from 7.0 to 9.6 hours with
      a volume of distribution that approximated the serum volume. No antibodies to
      rhuMAb CD18 were detected. A transient, dose-dependent increase in the WBC count
      was observed, consistent with the expected effect of rhuMAb CD18 on leucocyte
      demargination. No increase in infection was observed. rhuMAb CD18 administered by
      IV bolus was well tolerated, with the exception of one febrile reaction.

PMID- 11968155
TI  - Front-line leadership. Sharing the wealth: creating future EMS leaders through
      effective management mentoring.

PMID- 11968156
TI  - Prehospital rounds. Hypertension after having a baby.
AB  - Peripartum cardiomyopathy is an infrequent form of congestive heart failure. It
      occurs in one out of every 3,000-15,000 live births. Since there are
      approximately four million deliveries in the U.S. each year, 250 to 1,350 women
      will be affected annually.

PMID- 11968157
TI  - Fluid resuscitation.

PMID- 11968158
TI  - Cutting ties with phone lines. Delivery system's physicians remotely access its
      hospital information system via the Internet, saving thousands of dollars.

PMID- 11968159
TI  - Needle exchange: friend or foe.

PMID- 11968160
TI  - Methadone treatment and needle use prevention.

PMID- 11968161
TI  - Global agencies call for US$2.5 billion in aid for victims of humanitarian
      crises.

PMID- 11968162
TI  - Rethinking care from the perspective of disabled people.

PMID- 11968163
TI  - Smoking: a genetic condition?

PMID- 11968164
TI  - Dietary saturated fats may not be harmful in the absence of other risk factors.

PMID- 11968165
TI  - Illinois's Medicare drug program called 1st stab at national reform.

PMID- 11968166
TI  - "Coming out" is a dangerous time: HIV among young gay men.

PMID- 11968167
TI  - Right of passage.

PMID- 11968168
TI  - Female street youth and prostitution.

PMID- 11968169
TI  - I have cardiovascular disease and my wife thinks we should avoid restaurants
      where smoking is allowed because of my heart condition. Is her concern
      reasonable?

PMID- 11968170
TI  - [Pachyonychia congenita. Molecular genetic analysis simplifies clinical
      classification in subtypes].

PMID- 11968171
TI  - [The angiogenesis inhibitor vasostatin. In tumor inhibiting doses there is no
      impaired wound healing in the mouse model].

PMID- 11968172
TI  - [Of mice and humans. Updates on susceptibility and tumor suppression of malignant
      melanoma].

PMID- 11968174
TI  - [Referral by name].

PMID- 11968173
TI  - [Plastic surgery coverage of skin defects].

PMID- 11968175
TI  - [Considerations of the Robert Koch Institute and its Task Force on minimizing a)
      known and b) theoretical risk for transmission of variant Creutzfeldt-Jakob
      syndrome by potentially contaminated medical products].

PMID- 11968176
TI  - [Outcome after cardiac arrest--evaluation of a hospital program of
      cardiopulmonary resuscitation after 12 months].

PMID- 11968177
TI  - [Acquiring private third party funding in medicine: Einbecker recommendations of
      the German Society for Medical Law].

PMID- 11968178
TI  - ["Biological" but deadly. Potential biological weapons].

PMID- 11968179
TI  - Principles for the justification of public health intervention.
AB  - OBJECTIVES: The objective of this paper is to discuss principles relevant to
      ethical deliberation in public health. METHODS: Conceptual analysis and
      literature review. RESULTS: Four principles are identified: The Harm Principle,
      The Principle of Least Restrictive Means, The Reciprocity Principle, and The
      Transparency Principle. Two examples of how the principles are applied in
      practice are provided. INTERPRETATION: The paper illustrates how clinical ethics
      is not an appropriate model for public health ethics and argues that the type of
      reasoning involved in public health ethics may be at potential variance from that
      of empirical science. Further research and debate on the appropriate ethics for
      public health are required.

PMID- 11968180
TI  - [Sanitary and relief activity of the Polish Red Cross in the repatriation and
      displacement action in the Western Pomeranian region].
AB  - The final period of World War II and the first months of peace were the time of
      massive migration of Polish and German population. The first stage of the Poles'
      repatriation from the territories taken over by the USSR to the liberated parts
      of Poland underwent in an organizational chaos, which resulted from poor
      coordination between the institutions responsible for this operation. In
      principle, the National Repatriation Office was in charge of the repatriation
      action. However, where the NRO had no branches or wanted a joint action, the
      Polish Red Cross took a vital part in sanitary and relief activities. They were
      particularly crucial in the western and northern regions of Poland, which faced
      three massive migration currents: the influx of Polish repatriates from the USSR,
      the return of concentration camp prisoners, POWs and slave workers from Germany
      and the displacement of the German population. Colonel Jan Cialowicz gave a brief
      resume of the role the Polish Red Cross played in the repatriation and
      displacement action: "... At the time when the foundations of the State of Poland
      were created in the Western Pomeranian Region, the Polish Red Cross was dressing,
      feeding and treating those who needed it most desperately, taking special care of
      the repatriates and children."

PMID- 11968181
TI  - [Establishment, system, and action of ophthalmology department between 1945-1970
      in Lodz].
AB  - Investigating history of establishment, system and action of Ophthalmology
      department, 25 years after the second World War has been an aim of this work. In
      this period this Department has been directed by prof. Janusz Sobanski
      constantly. Between 1945-1950 Department had been functioned within the framework
      of University of Lodz, but in 1950 it went in to structure Academy of Lodz.
      Ophthalmology Department had been leading lively diagnostic, treatment, training,
      instructional, didactic, preventive, scientific, and researching actions. To sum
      up there were 19 doctors graduated and 85 doctors received specialization in
      field of eye diseases. Treatment of squinting, glaucoma, rheumatical eye
      diseases, disappearance of eye nerve and pigmental retina degeneration has been
      an object of research particularly.

PMID- 11968183
TI  - [Doctor of medicine Awit Reniger (1853-1907) and his doctorate dissertation].
AB  - The author announced main details of Awit Reniger's life, main thesis and
      conclusions of his doctorate dissertation. Doctor's Thesis concerning:
      Pathological changes in the anatomy of marrow in cases of the phosphorus
      intoxication. This dissertation is not reported in S. Konopka's: Polish medical
      bibliography of the nineteenth century (1801-1900).

PMID- 11968182
TI  - [The artistic interests of Professor Tadeusz Ginko, M.D. PH.D.(1917-1984)].
AB  - Tadeusz Ginko was born on 2nd April, 1917 in Vilnius, where, in 1938, he began
      his studies at the Medical Faculty of the Stefan Batory University. He was
      granted his medical diploma at Kaunas University in 1941. During the Nazi
      occupation, he was a lecturer in clandestine study groups in Vilnius (1940-1942),
      served as a medic for the Polish Home Army troops (Armia Krajowa; 1942-1944), was
      a prisoner of war in Kaluga (1944-1946). After his return to Poland, he
      participated in the organisation of health care centres in Pila and Plonsk (1946
      1950). In the years 1950-1984, he worked for Silesian Medical Academy (SMA), in
      the Surgical Departments of Zabrze (till 1962) and Katowice (1963-1984). In 1951
      he became full professor. He died on 28th October, 1989. T. Ginko, the
      artistically gifted surgeon, was known for his unique caricatures of his friends,
      fellow prisoners, doctors and artists. He published two sketchbooks containing
      the caricatures of SMA professors and doctors. His interest in sculpture dates
      back to the Kaluga times. The sculpture series called "Gnomes" ("Gnomy") reflects
      his knowledge of people, their passions and faults; in the linden carvings called
      "Strugadla" he showed the depth of human suffering. He exhibited his works in SMA
      (1978), in Oblate parochial church in Katowice (1989), and also in Warsaw, Cracow
      and Turin. The caricatures by Professor evoke memories of the past. His
      sculptures, drawing upon his philosophical thought can be seen as the allegories
      of important historic events as well as Professor's professional and personal
      experiences.

PMID- 11968184
TI  - [A few recollections about my professors from the Medical Faculty of Stefan
      Batory University during the period of 1929-1939].

PMID- 11968185
TI  - A thymic precursor to the NK T cell lineage.
AB  - CD1d-restricted autoreactive natural killer (NK1.1+) T cells function as
      regulatory cells in various disease conditions. Using improved tetramer tracking
      methodology, we identified a NK1.1- thymic precursor and followed its
      differentiation and emigration to tissues by direct cell transfer and in situ
      cell labeling studies. A major lineage expansion occurred within the thymus after
      positive selection and before NK receptor expression. Surprisingly, cytokine
      analysis of the developmental intermediates between NK and NK+ stages showed a T
      helper cell TH2 to TH1 conversion, suggesting that the regulatory functions of NK
      T cells may be developmentally controlled. These findings characterize novel
      thymic and postthymic developmental pathways that expand autoreactive cells and
      differentiate them into regulatory cells.

PMID- 11968186
TI  - Current world literature. Infections of the immunocompromised host.

PMID- 11968187
TI  - Current world literature. Nosocomial and hospital-related infections.

PMID- 11968188
TI  - Bibliography. Current world literature. Drug allergy.

PMID- 11968189
TI  - Bibliography. Current world literature. Insect allergy.

PMID- 11968190
TI  - Bibliography. Current world literature. Genetics and epidemiology.

PMID- 11968191
TI  - Bibliography. Current world literature. Skin and eye.

PMID- 11968192
TI  - Bibliography. Current world literature. Primary immune deficiency disease.

PMID- 11968194
TI  - Bibliography. Current world literature. Upper airway disease.

PMID- 11968193
TI  - Bibliography. Current world literature. Immunotherapy.

PMID- 11968195
TI  - Bibliography. Current world literature. Mechanisms of allergy and adult asthma.

PMID- 11968196
TI  - Bibliography. Current world literature. Pediatric asthma and development of
      atopy.

PMID- 11968197
TI  - Bibliography. Current world literature. Occupational disease.

PMID- 11968198
TI  - Bibliography. Current world literature. Outcome measures.

PMID- 11968199
TI  - Bibliography. Current world literature. Food allergy.

PMID- 11968200
TI  - The Blue "divorce" ... good for you???

PMID- 11968201
TI  - Another look at hospital finances. Is Medical Assistance really the villain?

PMID- 11968202
TI  - Health care for retirees.

PMID- 11968203
TI  - Employee health promotion programs can help contain costs.

PMID- 11968205
TI  - Patient safety -- an idea whose time has come.

PMID- 11968204
TI  - Containing drug costs - a prescription for purchasers.

PMID- 11968206
TI  - Is hospital volume the way to measure quality outcomes?

PMID- 11968207
TI  - Kinetics of 5-enolpyruvylshikimate-3-phosphate synthase inhibition by glyphosate.
AB  - The herbicide glyphosate (N-phosphonomethyl glycine) is a potent reversible
      inhibitor of the 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase activity of
      the purified arom multienzyme complex from Neurospora crassa. Inhibition of the
      EPSP synthase reaction by glyphosate is competitive with respect to
      phosphoenolpyruvate, with K(i) 1.1 microM, and uncompetitive with respect to
      shikimate-3-phosphate. The kinetic patterns are consistent with a compulsory
      order sequential mechanism in which either PEP or glyphosate can bind to an
      enzyme: shikimate-3-phosphate complex.

PMID- 11968208
TI  - Lipids as a principle for the identification of archaebacteria.
AB  - The 'Archaebacteria' consist of several distinct subgroups including methanogens,
      extreme halophiles and specific thermoacidophiles. These bacteria are distinct
      from other bacteria with respect to their characteristic RNA compositions, the
      absence of muramic acid in the cell walls and the predominance of nonsaponifiable
      [correction of nonsaponifable] lipids. The lipid composition of the
      archaebacteria consists of isoprenoid and hydroisoprenoid hydrocarbons and
      isopranyl glycerol ether lipids. The pathways for the biosynthesis of the lipid
      components are those shared by most microorganisms and demonstrate a close
      relationship; however, an independent line of descent is indicated by the
      formation of the isopranyl glycerol ether lipids. This discontinuity formulates a
      point for delineating the early stages of biological evolution and for dividing
      bacteria into two subgroups.

PMID- 11968209
TI  - Late degeneration in rabbit tissues after irradiation by heavy ions.
AB  - In 1974, using the rabbit as a model, we began long-term experiments designed to
      help in the evaluation of the hazards to man from extended exposure to heavy ions
      in space. Such exposure would occur, for example, during the construction of
      solar power stations in stationary orbits or on round trips to Mars. Our
      experiments with 400 MeV/nucleon Ne ions and 570 MeV/nucleon Ar ions have shown
      that true late effects of a degenerative nature are manifested only years after
      irradiation. At the appropriate doses (the high end of the experimental dose
      range), the magnitudes of the late effects are comparable with those encountered
      in human patients given radiation therapy with neutrons. Such comparisons show
      that the rabbit experiments are applicable to man. Given that basis, the results
      from the low end of the experimental dose range lead to the conclusion that
      astronauts subjected to the radiation fluxes anticipated during flights of the
      above duration could experience late radiation effects one or more decades after
      exposure. Late degenerative changes will occur in tissues of the central nervous
      system, terminally differentiating systems and stem cell populations. The studies
      also indicate that individual tissues may be "prematurely aged" by radiation in
      the sense that the "life spans" of those tissues can be decreased without the
      appearance of malignancies.

PMID- 11968210
TI  - Organic compounds in meteorites.
AB  - Recent studies of carbonaceous chondrites provide evidence that certain organic
      compounds are indigenous and the result of an abiotic, chemical synthesis. The
      results of several investigators have established the presence of amino acids and
      precursors, mono- and dicarboxylic acids, N-heterocycles, and hydrocarbons as
      well as other compounds. For example, studies of the Murchison and Murray
      meteorites have revealed the presence of at least 40 amino acids with nearly
      equal abundances of D and L isomers. The population consists of both protein and
      non-protein amino acids including a wide variety of linear, cyclic, and
      polyfunctional types. Results show a trend of decreasing concentration with
      increasing carbon number, with the most abundant being glycine (41 n Moles/g).
      The monocarboxylic acids are more abundant (1.83 micro Moles propanoic acid/g
      Murchison), with hydrocarbons present in even greater abundance. In addition,
      quantification of the monocarboxylic acids shows a nearly equal distribution of
      straight and branched chain isomers. These and other results to be reviewed
      provide persuasive support for the theory of chemical evolution and provide the
      only natural evidence for the protobiological subset of molecules from which life
      on earth may have arisen.

PMID- 11968211
TI  - Further studies on the environmental capabilities of fungi: interactions of
      salinity, ultraviolet irradiation, and temperature in Penicillium.
AB  - A strain of Penicillium currently under study in this laboratory has revealed
      some unexpected features in response to salts and UV-radiation. These responses
      include: (a) stimulation of growth by one molar NaCl and KCl at 23 degrees but
      not at 5 degrees C, (b) total inhibition by LiCl and RbCl at 5 degrees but not at
      23 degrees C, (c) stimulation by 254 nm radiation (2 x 10(6) erg cm-2 min-1, 30
      90 minutes) at 23 degrees and 5 degrees C, and (d) very elevated growth rates at
      23 degrees after incubation at 5 degrees C.

PMID- 11968212
TI  - The contribution of cometary volatiles to the primitive Earth.
AB  - It has been estimated that during its early history the Earth captured a mass of
      cometary material of the order of 10(23) grams. Since carbon is supposed to be at
      least three times more abundant in comets than in carbonaceous chondrites (3.5% C
      in C 1 chondrites), it can be deduced that about 1 x 10(22) grams of carbon (as
      carbon compounds), was added by comets to the surface of the prebiotic Earth.
      This carbon value is of the same order of magnitude as the value of the organic
      carbon buried in the Earth's sedimentary shell, but approximately one order of
      magnitude lower than the Earth's surface total carbon (7 x 10(22) gm). The
      capture of comets by the Earth would also have contributed to generating the
      appropriate aqueous and reducing environmental conditions necessary for organic
      synthesis. Although it is possible that some of the cometary carbon compounds
      falling on the Earth survived, most of them were probably decomposed by the heat
      and shock waves of the cometary collision. Upon quenching to low temperatures,
      however, the reactive chemical species produced by the impact would have
      recombined, leading to the synthesis of a great variety of organic molecules.
      Laboratory experiments with radiation, heat and shock waves have demonstrated
      that some of the synthesized compounds are biochemical molecules: amino acids,
      sugars, purines, and pyrimidines. These are essential to all living systems.

PMID- 11968213
TI  - The influence of life on the evolution of the atmosphere.
AB  - The early history of life on earth may have been characterized by coevolution of
      microbial metabolism and atmospheric composition. Metabolic developments affected
      the composition of the atmosphere, and the resulting changes in the atmosphere
      stimulated the evolution of new metabolic capabilities. The first organisms eked
      out an existence by deriving energy from the fermentation of organic compounds
      abiotically synthesized. The abiotic source was meager, however, and when
      autotrophy arose, life was freed from its dependence on abiotic synthesis. The
      expanded level of biological activity made possible by autotrophy resulted in an
      increased rate of burial of reduced organic matter in sea floor sediments. The
      resultant drain on the concentration of electron donors in the biosphere caused a
      decline in the hydrogen content of the atmosphere. Biological productivity was
      limited by the supply of reduced compounds. This paper explores the
      biogeochemical circulation of electron donors in the primitive anaerobic ocean,
      concluding that their shortage was so critical as to provide strong selective
      pressure for the evolution of algal photosynthesis.

PMID- 11968214
TI  - Life sciences and space research volume XVIII. Proceedings of the Open Meeting of
      the Working Group on Space Biology of the Twenty-second Plenary Meeting of
      COSPAR, Bangalore, India, 29 May-9 June 1979.

PMID- 11968215
TI  - [Development of pharmaceutical supply business in Hokkaido].

PMID- 11968216
TI  - [Historical study of a moth repellent, "Fujisawa Camphor" (2) manufacture of
      borneol].
AB  - The manufacture of borneol started in about 1890 by the reduction of camphor at a
      rural chemical work in Osaka. Fujisawa Company, which refined and sold crude
      camphor, began to study the techniques necessary to manufacture borneol. In 1912,
      Fujisawa had succeeded in producing high-quality borneol in its plant. They tried
      to export it to China, from where they imported it before. The company replaced
      natural borneol on the market, supplying large amounts of high-quality borneol
      produced by the reduction method.

PMID- 11968217
TI  - [A botanical research worker in Bitchu Province (Okayama Prefecture) Yoshino
      Zensuke].
AB  - Yoshino Zensuke (1877.5 5-1964. 12. 11) helped in his father's drugstore after
      his graduation from Takahashi Higher Primary School. He developed a great
      interest in roadside plants while traveling on business ordering and delivering
      for the store drugs and gradually become one of the most famous botanical
      research workers in Bitchu Province. The author has explored Zensuke's life and
      work in detail.

PMID- 11968218
TI  - [Historical investigation of dentifrice in China].
AB  - A herbal literature survey was carried out on data concerning historical
      pharmacognostical changes of "dentifrice" in China and how diseases of the teeth
      and gums had been treated there in ancient times. It had been considered to be a
      matter of utmost importance that to prevent teeth from decaying, only the
      brushing of teeth with a toothbrush was necessary. Over time, various tooth
      agents have been found to treat oral diseases the teeth and gums. Glycyrrhizae
      Radix, Ginseng Radix, Scutellariae Radix, Menthae Herbal, and salt were widely
      used materials. Investigations from all approaches are being carried out to
      develop remedies for oral diseases, including Kampo medicine and the
      pharmacological effects of numerous crude drugs. When tracing the
      pharmacognostical changes of dentifrice in ancient China, we felt wonder at and
      admiration for the abundance of clinical experiences described in the old herbal
      and medical literature we researched.

PMID- 11968220
TI  - [The 50-year history of PAS production at Tanabe Seiyaku].
AB  - More than 50 years have passed since Tanabe Seiyaku Co., Ltd. (Tanabe) started
      producing PAS series (para-aminosalicy-late), which is one of the typical
      antituberculous agents. NIPPAS series, Tanabe's PAS was produced by the enormous
      efforts of Tanabe's researchers and engineers in the 1950s, and it made a great
      contribution to the remedy for many tuberculars. After that, the prominent
      progress of antituberculous agents, medical technology, and public hygiene
      dramatically decreased the member of tubercular patients, and usage of the PAS
      series was also on the decrease year by year. Most recently, tuberculars are
      unfortunately increasing gradually and the NIP-PAS series holds an important
      position as a prominent remedy for this disease. Therefore Tanabe still produces
      NIPPAS. This paper describes the historical process of NIPPAS production of
      Tanabe.

PMID- 11968219
TI  - [A 50-year history of new drugs in Japan: the developments and trends of
      antihyperlipidemic drugs].
AB  - The developments and trends of antihyperlipidemic drugs and their effects on the
      mortality of coronary heart disease in Japan were investigated. The developed
      drugs available for hyperlipidemia were recorded with their approval dates by the
      Ministry of Health and Welfare (Table 1). 1. Antihyperlipidemic drugs have been
      developed since the late 1950s. Useful drugs among them include the fibrate
      series and the statin (HMG-CoA reductase inhibitor) series. Clofibrate, developed
      in 1965, was the first fibrate drug, and pravastatin sodium (Mevalotin(R) Sankyo
      Co.), developed in 1989, was the first statin drug. They have sure effectiveness
      for lowering serum cholesterol and triglyceride. But they induce an unfavorable
      side-effect, rhabdomyolisis, especially after the continuous or simultaneous use
      of both. The other drug classes using hyperlipidemia include various different
      types, e.g., probucol, nicotinates, anion exchange resins, ethyl icosapentate,
      and dextran sodium sulfate. Despite their mild activities, the low incidence of
      adverse effects make them suitable for supplementary use with fibrates or
      statins. 2. "Guideline for Diagnosis and Treatment of Hyperlipidemia in Adult"
      was presented by the Japan Atherosclersis Society in 1997. The standard criteria
      of serum cholesterol and triglyceride levels in Japanese adults were proposed.
      The hypercholesterolemia is the state of more than a 220 mg/dl level of serum
      cholesterol, and hypertriglyceridemia is of more than a 150 mg/dl level of serum
      triglyceride. The pharmacotherapy should be applied for a high serum level of
      cholesterol exceeding 240 mg/dl. But the standard routine formula of drug therapy
      were not indicated in the present guideline. 3. Epidemiological surveys show that
      hyperlipidemia induces coronary heart diseases in the United States, European
      countries, and Japan. The mortality of all heart disease patients in Japan
      increased rapidly from the late 1960s, but the mortality resulting from coronary
      heart disease was suppressed from 1968. This suppression continued throughout
      1994 when artificial statistical changes occurred. It may be due to the newly
      developed antihyperlipidemic drugs, e.g., the clofibrate group, the statin
      series, and others (Fig.2).

PMID- 11968221
TI  - [A challenging history of pharmaceutical education in Hokkaido].

PMID- 11968222
TI  - Extracorporeal immunoadsorption treatment for rheumatoid arthritis.
AB  - Immunoadsorption treatment is a non-drug therapy for rheumatoid arthritis. The
      treatment is based on filtering the patient's plasma through a column containing
      staphylococcal protein A. The treatment is effective in alleviating the symptoms
      of severe rheumatoid arthritis in some patients. Data on long-term outcomes are
      not available. The mechanism of action of this treatment is unclear. Most adverse
      effects are associated with the apheresis procedure. The cost per 12 week course
      of treatment is likely to be more than C $20,000. The cost-effectiveness of the
      technology is not yet established.

PMID- 11968223
TI  - Anaesthetics. Painful doubts about practice.

PMID- 11968224
TI  - Sexually transmitted infection. Return of the dirty dozen.

PMID- 11968225
TI  - Why are women who are eating healthily getting fatter?

PMID- 11968226
TI  - Long-term care. Plans to mend patchy care home nursing.

PMID- 11968228
TI  - Superficial wounds.

PMID- 11968229
TI  - Happy nappy chappy.

PMID- 11968227
TI  - Does the NHS need celebrity chefs to spice up hospital food?

PMID- 11968230
TI  - HVs need specialist care and attention.

PMID- 11968231
TI  - Clearing the waters over hygiene debate.

PMID- 11968232
TI  - Skill mixture does not mean loss of status.

PMID- 11968233
TI  - I drink, therefore I am.

PMID- 11968234
TI  - Cancer care comes of age.

PMID- 11968235
TI  - A forerunner to NHS Direct.

PMID- 11968236
TI  - Government must end dangerous practice of using students to plug staff gaps.

PMID- 11968237
TI  - An audible difference.

PMID- 11968238
TI  - Perfect 10. Nurses should be able to prescribe medicines.

PMID- 11968239
TI  - A weighty issue.

PMID- 11968240
TI  - Therapeutic care.

PMID- 11968241
TI  - Munchausen's by proxy. Nurses warned on spy videos.

PMID- 11968242
TI  - Promoting excellence in the care of older people: case report. 3.

PMID- 11968243
TI  - Toxic epidermal necrolysis.
AB  - Although Ms Weeks was supported throughout this period, we were concerned that
      she would require further psychological help. At the end of her stay she decided
      that she did not require help. However, she knew that if at a later date she
      changed her mind, it would be arranged. Ms Weeks was offered an appointment with
      the Red Cross camouflage service, which was on hand to offer advice about
      appropriate techniques to hide the hyperpigmentation on her face and other
      exposed areas, but this again was declined. Ms Weeks was in ICU for three-and-a
      half weeks and her skin healed well. She was left with multihyperpigmented skin,
      which over time may resolve itself.

PMID- 11968244
TI  - Nebulisers--1: Preparation.

PMID- 11968246
TI  - Employment tribunal. I was made a scapegoat, says race case nurse.

PMID- 11968245
TI  - Staff shortages. Fears for patient safety as nursing students 'regularly left in
      charge'.

PMID- 11968247
TI  - Education chiefs to probe soaring drop-out ... but admissions hit all-time high.

PMID- 11968248
TI  - Immunisation. Meningitis C vaccine programme hailed a success.

PMID- 11968249
TI  - Dulling the pain won't justify late abortion.

PMID- 11968251
TI  - Scheme pioneers home drugs for child cancers.

PMID- 11968250
TI  - Nurse defeats bullying charge.

PMID- 11968252
TI  - Alternative career for disabled nurses.

PMID- 11968253
TI  - Smoking cessation. Can we help you quit?

PMID- 11968254
TI  - Dublin looks over the water in search of nurses.

PMID- 11968255
TI  - Nursing homes. Oldies but goldies.

PMID- 11968256
TI  - Education. Fancy studying in Finland or Greece? Now it's a real option.

PMID- 11968257
TI  - Are patients put at risk by nurses and doctors with poor language skills?

PMID- 11968258
TI  - Lessons from Leon and Lily.

PMID- 11968259
TI  - Registration can prove a nursing liability.

PMID- 11968260
TI  - Nursing a grievance against a lack of training.

PMID- 11968261
TI  - Uneasy bedfellows.

PMID- 11968262
TI  - Up in the air.

PMID- 11968263
TI  - Perfect 10. Introducing an urgent-needs assessment system.

PMID- 11968264
TI  - Asthma care in a school environment.

PMID- 11968265
TI  - Excellence in the care of older people: case report. 4.

PMID- 11968266
TI  - Cancer patients' information needs.

PMID- 11968267
TI  - Pay review body submissions. Midwives need carrot to return to NHS.

PMID- 11968268
TI  - Nebulisers--2: Administration.

PMID- 11968269
TI  - The stomach for it.

PMID- 11968270
TI  - Midwifery. Fathers praise HVs, pan midwives.

PMID- 11968271
TI  - Violence at work. 'Stabbed with my own scissors'.

PMID- 11968272
TI  - Education. On the wards in eight weeks.

PMID- 11968273
TI  - Mental health. Wrestling with demons ended in tragedy.

PMID- 11968274
TI  - Would you be willing to nurse Saddam Hussein?

PMID- 11968275
TI  - Leading questions.

PMID- 11968278
TI  - Nurse prescribing is falling behind.

PMID- 11968279
TI  - This one's personal.

PMID- 11968280
TI  - Security alert.

PMID- 11968281
TI  - Why nurses make good foster parents.

PMID- 11968282
TI  - One of the team.

PMID- 11968283
TI  - Making and receiving referrals.

PMID- 11968284
TI  - A PEG service with nurses at its heart.

PMID- 11968286
TI  - The benefits of a nurse-led preoperative assessment clinic.
AB  - OPAC has proved itself a valuable service, not only to patients but also in
      ensuring the efficient management of these patients' care throughout their
      contact with the hospital. It has been shown that a registered nurse is able to
      use this service as a means of identifying a variety of problems that can affect
      patient admission and use this foresight to alleviate patient concerns, plan to
      enable early discharge and minimise lost and disrupted theatre times. This post
      has since become a regular provision within the orthopaedic service, funded by
      the trust, and is a routine service provided to all orthopaedic patients due to
      undergo elective orthopaedic surgery. In addition, the clinic monitors waiting
      lists and removes those patients who no longer require or wish to have surgery.
      Quality care is provided promptly and efficiently on a one-to-one basis and
      patients experience minimum disruption due to the centralisation of clinic
      services. Nurse-led clinics appear more cost-effective as they employ a senior
      nurse instead of a consultant or anaesthetist and this is achieved without losing
      the quality of patient care. In the new, modern and dependable NHS, nurse-led
      clinics are the way forward.

PMID- 11968287
TI  - UK's first 'wellness centre' takes preventive action.

PMID- 11968288
TI  - A critical care specialist practitioner programme.

PMID- 11968289
TI  - Bladder ultrasound.

PMID- 11968290
TI  - Rock steady nurse.

PMID- 11968294
TI  - Search for drug information: technology implications for rural consumers and
      pharmacies.
AB  - As they age, baby boomers represent a larger proportion of the population
      experiencing health-related problems. As such, they are growing users of
      prescription medications. With pharmaceutical companies increasing their use of
      the Internet for direct-to-consumer advertising, and boomers leading in the
      routine use of technology, a shift in the sources used to obtain drug information
      may occur. Analyzing data from a panel of rural Illinois residents, this paper
      examines some aspects of the current dynamics of prescription drug information
      sources and their consequences for rural consumers and pharmacies.

PMID- 11968295
TI  - Improving knowledge of strategic goals and the impact on organizational
      commitment.
AB  - A large health maintenance organization (HMO) in San Diego, California developed
      a year-long communication plan to increase employee knowledge of the company's
      strategic goals and enhance organizational commitment. Survey results indicated:
      Respondents remembered significantly more strategic goals after program
      implementation. Respondents who had personal involvement in achieving goals
      remembered significantly more goals than those without involvement. Department
      meetings and the employee/physician newsletter were identified as primary sources
      for learning about goals. These findings suggest that organizations may be able
      to strengthen employee commitment by increasing awareness of the organization's
      strategic goals and encouraging employees to become personally involved in the
      achievement of those goals.

PMID- 11968296
TI  - A comparison of medical professionals with favorable and unfavorable attitudes
      toward advertising: an empirical study.

PMID- 11968297
TI  - The Internet and hospital marketing strategy: a survey.
AB  - This project, which was conducted in the U.S. using a large number of healthcare
      organizations, is an attempt to discover if we can find any evidence of the
      impact of marketing theories on the real world of healthcare organizations. This
      paper addresses three major themes: Do healthcare organizations have an Internet
      strategy? Are they using the Internet in a strategic fashion? Can we identify any
      difference among the sectors concerning the strategic use of the Internet?
      Finally, implications for further research and health care practices are
      highlighted as well.

PMID- 11968298
TI  - AIDS public service announcements: effects of fear and repetition on predictors
      of condom use.
AB  - An experiment examined the effects of varying levels of fear and message
      repetition in a radio public service announcement (PSA) on attitudes toward and
      intentions to use condoms. Predictions were derived from the Theory of Reasoned
      Action and Fazio's accessibility model. Results suggest that repetition and fear
      have important effects on intentions to use condoms and attitudes toward using
      condoms, even after accounting for inputs specified by the Theory of Reasoned
      Action In addition, frequency affected the relative weights of attitudinal versus
      normative effects on intentions, suggesting that PSAs may be able to affect
      attitudes and intentions through spontaneous attitude activation as described by
      Fazio (1990).

PMID- 11968299
TI  - Physicians' and consumers' conflicting attitudes toward health care advertising.
AB  - The purpose of this paper is to explore the conflicting attitudes held by
      physicians and health care consumers toward health care advertising in an attempt
      to resolve the question. The paper introduces the differing positions held by the
      two groups. The rationale behind physicians' attitudes is then presented that
      advertising can be unethical, misleading, deceptive, and lead to unnecessary
      price increases. They believe that word-of-mouth does and should play the major
      role in attracting new patients. The opposite view of consumers is then presented
      which contends that health care advertising leads to higher consumer awareness of
      services, better services, promotes competitive pricing, and lowers rather than
      raises health care costs. The final section of the paper compares the arguments
      presented and concludes that health care advertising clearly has a place in the
      health care industry.

PMID- 11968300
TI  - Exploring the relevance of localization in anti-drinking and driving PSAs:
      factors that may influence college students' behaviors.
AB  - This article generalizes the results of a qualitative study, which suggested that
      localization of consequences in PSAs may have a impact on reducing the incidence
      of drunk driving among college students. The results of the current study suggest
      that this implication may be true. The results also suggest that frequency of
      binge drinking, gender, and age are factors that influence perceptions of drunk
      driving risk, and that PSAs need to take these factors into account in order to
      be effective.

PMID- 11968302
TI  - Are nurses their own worst enemy?

PMID- 11968301
TI  - Patient satisfaction and health status.
AB  - This paper examines the relationship between satisfaction and functional health
      status of the patient. Based on a sample of 463 patients from three hospitals,
      there was no relationship between the physical component summary score of the SF
      36 and overall Press, Ganey patient satisfaction score. There was a weak negative
      relationship between the mental health component summary score of the SF-36 and
      the Press, Ganey patient satisfaction score. Similar patterns were observed when
      the relationships between functional status and patient satisfaction are examined
      for specific treatment groups. The strength of the relationship between mental
      health and satisfaction was slightly stronger for cardiology patients. Among
      obstetrics patients there was no relationship between either health status
      measure and satisfaction. A weak positive relationship between physical health
      status and patient satisfaction was observed among medical/surgical patients.
      Based on the weak or non-existent relationships between the variables, patient
      satisfaction does not appear to be influenced by the health of the patient when
      discharged.

PMID- 11968304
TI  - Nurse shortages a global issue.

PMID- 11968303
TI  - Inspections. It's nothing personal.

PMID- 11968306
TI  - Is offering cash payments the answer to recruitment problems?

PMID- 11968305
TI  - Guidelines aim to halt child abuse. Interview by Caroline Ryan.

PMID- 11968307
TI  - Time to block the brain-drain.

PMID- 11968311
TI  - Speaking the unspeakable.

PMID- 11968312
TI  - Shock of the new.

PMID- 11968313
TI  - Model behaviour.

PMID- 11968314
TI  - Learning disabilities. Our friends in the north.

PMID- 11968315
TI  - Discharging patients and bed management.

PMID- 11968316
TI  - Why honesty is the best policy.

PMID- 11968317
TI  - A joint learning venture between new nurses and junior doctors.

PMID- 11968318
TI  - Working with families of forensic patients.

PMID- 11968320
TI  - A new model of preregistration nursing education and training.

PMID- 11968319
TI  - A guide to treating lymphoedema.

PMID- 11968321
TI  - The role of a dementia trailblazer.

PMID- 11968322
TI  - Measuring peak expiratory flow.

PMID- 11968328
TI  - [Why do patients with functional dyspepsia have symptoms?].

PMID- 11968329
TI  - [What is functional dyspepsia? Concept and classification].

PMID- 11968330
TI  - [Does Helicobacter pylori infection cause dyspepsia in the absence of ulcer?].

PMID- 11968331
TI  - [Dyspepsia and non-steroidal anti-inflammatory agents: not everything is an
      ulcer].

PMID- 11968333
TI  - [Treatment of functional dyspepsia].

PMID- 11968332
TI  - [How should patients with dyspepsia be evaluated? An evidence-based approach].

PMID- 11968334
TI  - [Should Helicobacter pylori be eradicated in patients with functional
      dyspepsia?].

PMID- 11968335
TI  - [Future perspectives in functional dyspepsia: new treatments on the horizon].

PMID- 11968336
TI  - [Functional dyspepsia: a common problem in primary care].

PMID- 11968337
TI  - [Chronic cholestasis. Cholangitis].

PMID- 11968338
TI  - [Primary sclerosing cholangitis].

PMID- 11968339
TI  - [Autoimmune cholangitis].

PMID- 11968340
TI  - [Medical treatment of chronic cholestasis: ursodeoxycholic acid].

PMID- 11968341
TI  - [Indications and results of liver transplantation in cholestatic diseases].

PMID- 11968342
TI  - [Pathophysiology of biliary epithelium in primary biliary cirrhosis].

PMID- 11968343
TI  - [Treatment of chronic hepatitis C. Combined treatment in naive patients].

PMID- 11968344
TI  - [Treatment of chronic hepatitis C relapse].

PMID- 11968345
TI  - [Treatment of chronic hepatitis C in patients not responding to interferon].

PMID- 11968346
TI  - [Economic evaluation of combined therapy in chronic hepatitis C].

PMID- 11968347
TI  - [Treatment of recurrent hepatitis C].

PMID- 11968348
TI  - [Chronic hepatitis C. Treatment of special groups].

PMID- 11968349
TI  - [Recurrence of autoimmune liver disease after liver transplantation].

PMID- 11968350
TI  - [Recurrence of chronic cholestatic liver diseases following liver
      transplantation].

PMID- 11968351
TI  - [Recurrence of non-malignant disease after liver transplantation: hepatitis B].

PMID- 11968352
TI  - [Recurrence of hepatitis C after liver transplantation].

PMID- 11968353
TI  - Working life. Why are we waiting?

PMID- 11968354
TI  - Nursing education. Laptop of luxury for students.

PMID- 11968355
TI  - It's beastly what they think of health visitors.

PMID- 11968356
TI  - Is there any substitute for experience?

PMID- 11968357
TI  - Choosing the public face of the RCN.

PMID- 11968358
TI  - Clot busters set door-to-needle time for heart attack response.

PMID- 11968359
TI  - Cesareans are not just life-savers.

PMID- 11968361
TI  - Serious drug error taught me the need to brush up my maths.

PMID- 11968360
TI  - Insight into dementia.

PMID- 11968363
TI  - Don't call us--and we won't call you.

PMID- 11968362
TI  - School nurses deserve a pat on the back.

PMID- 11968364
TI  - Tales from Tashkent.

PMID- 11968365
TI  - New brooms and old hands.

PMID- 11968366
TI  - Learn a lesson from teachers--and pay nursing students.

PMID- 11968367
TI  - Perfect 10. Carrying out defibrillation.

PMID- 11968368
TI  - Delivering chemotherapy in rural areas: can it work?

PMID- 11968369
TI  - Patient compliance.

PMID- 11968370
TI  - Excellence in the care of older people: case report. 2.

PMID- 11968371
TI  - Postnatal exercise.

PMID- 11968372
TI  - Introducing care pathways.

PMID- 11968373
TI  - Systems & diseases. Exploring normal anatomy and physiology. Nervous system. 1.

PMID- 11968374
TI  - Students demand salaries.

PMID- 11968375
TI  - Drug ruling. RCN gets nasty over NICE decision.

PMID- 11968376
TI  - Nurses' virus exposure soars.

PMID- 11968377
TI  - Nursing homes. Call for care home training.

PMID- 11968378
TI  - Nurse charged with poisoning.

PMID- 11968379
TI  - Scissors attack. Assault on HCA 'not an isolated case'.

PMID- 11968380
TI  - Do yourself a favour: vote to register HCAs.

PMID- 11968381
TI  - Forensic nursing. Nurse to examine sex crime victims.

PMID- 11968382
TI  - Profile. Back from the brink.

PMID- 11968384
TI  - Mental health.

PMID- 11968383
TI  - One-stop shop for sexual health.

PMID- 11968386
TI  - Cancer screening. What the eye doesn't see.

PMID- 11968385
TI  - US elections. Candidates talking, dead men walking.

PMID- 11968387
TI  - Should ward leaders have direct control over domestic services?

PMID- 11968388
TI  - Elderly and counting on the NHS.

PMID- 11968389
TI  - How to defuse the smart bombs.

PMID- 11968390
TI  - Confronting child abuse.

PMID- 11968391
TI  - Follow the leader?

PMID- 11968392
TI  - Revolution in the wards.

PMID- 11968393
TI  - What do practice nurses do?

PMID- 11968394
TI  - The grass always looks greener.

PMID- 11968396
TI  - Damage limitation.

PMID- 11968395
TI  - Perfect 10. Managing your own patient caseload.

PMID- 11968397
TI  - Health visiting. Identity crisis for HVs.

PMID- 11968398
TI  - Breast-feeding: overcoming the barriers.

PMID- 11968399
TI  - Encouraging mothers to start breast-feeding.

PMID- 11968400
TI  - Promoting excellence in the care of the older person: case report 1.

PMID- 11968401
TI  - Psychiatric nurses granting leave: a tool to help.

PMID- 11968402
TI  - A practical guide to giving Entonox.

PMID- 11968403
TI  - Public health. HVs praise report's forward thinking.

PMID- 11968404
TI  - Good riddance to dosh-obsessed doctors.

PMID- 11968406
TI  - Nurses on board fast-track teams to tackle heart attacks.

PMID- 11968405
TI  - Health and safety. Nurses' anger at rat plague.

PMID- 11968407
TI  - The great petrol rip-off.

PMID- 11968408
TI  - Nursing and Midwifery Council. Dodgy docs force nurse crackdown.

PMID- 11968409
TI  - Cancer services.

PMID- 11968410
TI  - Asset management is key to plan's success.

PMID- 11968411
TI  - Has the move towards patient empowerment gone too far?

PMID- 11968413
TI  - Pity you got it wrong on disability.

PMID- 11968412
TI  - Systems fail, not just individuals.

PMID- 11968414
TI  - RCN can't defend me.

PMID- 11968415
TI  - Crisis in intensive care bodes ill for winter pressure.

PMID- 11968416
TI  - Bad news makes for better nursing.

PMID- 11968417
TI  - Nursing's ripping yarns.

PMID- 11968418
TI  - Perfect 10.

PMID- 11968419
TI  - Independent nurse specialists.

PMID- 11968420
TI  - A taste of one's own medicine.

PMID- 11968421
TI  - Out of Africa.

PMID- 11968422
TI  - Skin cancer: the future.

PMID- 11968423
TI  - Malignant melanoma: the surgical approach.

PMID- 11968424
TI  - Giving evidence: why and how.

PMID- 11968425
TI  - A health website for children.

PMID- 11968426
TI  - A practical guide to ear syringing.

PMID- 11968427
TI  - Communicating with people from different cultures.

PMID- 11968428
TI  - Attack on NHS Direct sparks probe.

PMID- 11968429
TI  - Gay nurses fight pension rules.

PMID- 11968430
TI  - Disciplinary action. 'No authority' nurse struck off.

PMID- 11968431
TI  - Long-term care is the essence of New Labour.

PMID- 11968432
TI  - Doctors vindicate GP who 'swapped roles' with nurse.

PMID- 11968433
TI  - Human rights. Court win for lesbian nurse.

PMID- 11968434
TI  - The contribution of C. David Marsden to the study and treatment of myoclonus.

PMID- 11968435
TI  - Physiology of negative myoclonus.

PMID- 11968436
TI  - Palatal tremor: the clinical spectrum and physiology of a rhythmic movement
      disorder.

PMID- 11968437
TI  - Overview, history, and classification of myoclonus.

PMID- 11968438
TI  - Dissection of the cerebello-olivary projection does not induce neuronal
      hypertrophy in the inferior olive in the rat.

PMID- 11968439
TI  - Pathophysiology of spinal myoclonus.

PMID- 11968440
TI  - Restless legs syndrome and periodic limb movements.

PMID- 11968441
TI  - Neurophysiology of the startle syndrome and hyperekplexia.

PMID- 11968442
TI  - Genetics of idiopathic myoclonic epilepsies: an overview.

PMID- 11968443
TI  - Inherited myoclonus-dystonia.

PMID- 11968444
TI  - Epidemiology of myoclonus.
AB  - All studies that attempt to evaluate the general occurrence of myoclonus have
      various biases. Even so, myoclonus has been demonstrated to be an important cause
      of abnormal movement control when compared to other movement disorders. Clearly,
      posthypoxia etiology, neurodegenerative disease, and epilepsy syndromes are
      important individual causes of myoclonus. The epidemiology of myoclonus is worthy
      of further study in other defined populations.

PMID- 11968445
TI  - Clinical features and genetics of Unverricht-Lundborg disease.

PMID- 11968446
TI  - Progressive myoclonus epilepsy with polyglucosan bodies: Lafora disease.

PMID- 11968447
TI  - Clinical features and molecular genetic basis of the neuronal ceroid
      lipofuscinoses.

PMID- 11968448
TI  - Clinical features and genetics of myoclonic epilepsy with ragged red fibers.

PMID- 11968449
TI  - Myoclonus in Lewy body disorders.

PMID- 11968450
TI  - Dentatorubral-pallidoluysian atrophy: clinical aspects and molecular genetics.

PMID- 11968451
TI  - The role of the serotonin system in animal models of myoclonus.

PMID- 11968452
TI  - Involvement of gamma-aminobutyric acid in myoclonus.

PMID- 11968453
TI  - The role of glycine and glycine receptors in myoclonus and startle syndromes.

PMID- 11968454
TI  - The isolated rat spinal cord as an in vitro model to study the pharmacologic
      control of myoclonic-like activity.

PMID- 11968455
TI  - The pacemaker in posthypoxic myoclonus: where and what to do about it?

PMID- 11968456
TI  - Posthypoxic myoclonus animal models.
AB  - The animal model presented here resembles several of the key features of human
      myoclonus. Further study of the neuropathology and pharmacology of this animal
      model will hopefully increase our knowledge of the brain structures and systems
      affected in this disease and permit testing of therapeutic agents for the
      significant number of patients who do not respond to current treatments.

PMID- 11968457
TI  - The serotonin hypothesis of myoclonus from the perspective of neuronal
      rhythmicity.
AB  - A quantitative analysis of two rat syndromes of myoclonus are presented, modeling
      myoclonic epilepsy and postanoxic myoclonus. Like the human conditions, both of
      the models benefit therapeutically from drugs that act on the serotonin system.
      The rat model of myoclonic epilepsy is associated with a profound loss of
      serotonin throughout the brain (except in the striatum) and is generated by an
      oscillator that is synchronized around the midline. The rat model of posthypoxic
      myoclonus does not demonstrate a significant reduction in serotonin in any
      location of its brain and is generated by a non-oscillating circuit in the
      medulla. Although some forms of myoclonic epilepsy may benefit from serotonin
      drugs because they are caused by a decrease in brain serotonin, our data indicate
      that posthypoxic myoclonus is not caused by a decrease in the serotonergic
      innervation of any region of the brain. That the raphe nuclei do not degenerate
      after global brain ischemia was noted by C. David Marsden in a discussion of the
      histologic findings of three of his human cases of posthypoxic myoclonus (page
      117 of reference 10) and led him to question the hypothesis that posthypoxic
      myoclonus was due to a loss of serotonin neurons. Our data confirm his
      observation in the rat, but also indicate that density of serotonin fibers and
      terminals throughout the brain is not reduced by the brain ischemia that produces
      posthypoxic myoclonus. It remains to be determined whether the physiologic
      responsiveness of serotonin neurons is altered by global brain ischemia and
      whether changes in serotonin release or serotonin receptor properties are
      associated with posthypoxic myoclonus. The stability of the serotonin system in
      posthypoxic myoclonic rats is remarkable when one considers the wide range of
      disorders that is produced by the prolonged brain ischemia. The inability of the
      most severely posthypoxic myoclonic rats to perform 7-Hz tongue protrusions
      indicates substantial physiologic disruption of brainstem motor function.
      Moreover, the posthypoxic myoclonic rat suffers from ataxia, seizures, retrograde
      amnesia, and impaired ability to learn. The wide spectrum of these deficits is
      sharply constrasted by its apparently intact serotonin system. We have identified
      the inferior olive as a locus that may generate the rhythmic components of tremor
      and myoclonus in syndromes that are truly associated with a dramatic loss of
      brainstem serotonin. Serotonin acts within the inferior olive to constrain its
      rhythmic firing. Without intraolivary serotonin, olivary neurons are predisposed
      to oscillate continuously, providing a substrate upon which sustained rhythmic
      spiking may be superimposed. It is clear that such unconstrained rhythmicity
      produces synchronized whole-body tremor at 10 Hz (33, 41-43). The effects of
      serotonin to suppress olivocerebellar rhythmicity are mediated by postsynaptic 5
      HT2 receptors that reduce the magnitude of the low-threshold calcium conductance,
      IT. It is notable that dysregulation of this conductance has been associated with
      hyper-rhythmic states in the thalamus underlying cognitive disorders ranging from
      depression to tinnitus (49), indicating a common mechanism underlying a variety
      of neurologic conditions. The identification of a specific brainstem locus
      (inferior olive), serotonin receptor 5-HT2, and ionic current IT involved in a
      form of rhythmic myoclonus may provide multiple clues toward which future
      pharmacotherapies can be directed.

PMID- 11968458
TI  - Neurodegenerative causes of myoclonus.

PMID- 11968459
TI  - Why do Purkinje cells die so easily after global brain ischemia? Aldolase C,
      EAAT4, and the cerebellar contribution to posthypoxic myoclonus.
AB  - The experiments strongly suggested that the reason why Purkinje cells die so
      easily after global brain ischemia relates to deficiencies in aldolase C and
      EAAT4 that allow them to survive pathologically intense synaptic input from the
      inferior olive after the restoration of blood flow. This conclusion is based on:
      (a) the remarkably tight correspondence between the regional absence of aldolase
      C and EAAT4 in Purkinje cells and the patterned loss of Purkinje cells after a
      bout of global brain ischemia; (b) the necessity of the olivocerebellar pathway
      for the ischemic death of Purkinje cells; and (c) the build-up of pathologically
      synchronous and high-frequency burst activity within the inferior olive during
      recovery from ischemia. Indeed, the correspondence between the absence of
      aldolase C and EAAT4 to sensitivity to ischemia could be demonstrated for zones
      of Purkinje cells as small as two neurons. A second finding was that Purkinje
      cells are not uniformly sensitive to transient ischemia, since they die most
      frequently in zones where aldolase C and EAAT4 are absent. One implication of the
      experiment is that factors beyond the unique synaptic and membrane properties of
      Purkinje cells play an important role in determining this neuron's high
      sensitivity to ischemia. The data strongly imply that two properties of Purkinje
      cells that make them susceptible to ischemic death are their reduced capability
      to sequester glutamate and reduced ability to generate energy during anoxia. The
      patterned death of Purkinje cells is sufficient to induce a form of audiogenic
      myoclonus, as determined with a neurotoxic dose of ibogaine. Ibogaine-induced
      myoclonus is recognized behaviorally as a reduced ability to habituate to a
      startle stimulus and resembles the myoclonic jerk of rats during recovery from a
      prolonged bout of global brain ischemia. Commonalities of ischemia and ibogaine
      induced neurodegeneration are the intricately striped Purkinje cell loss in the
      posterior lobe and a nearly complete deafferentation of the lateral aspect of the
      fastigial nucleus from the cerebellar cortex, in particular the dorsolateral
      protuberance. Thus, the data point strongly to a cerebellar contribution to
      audiogenic myoclonus. Single-neuron electrophysiology experiments in monkeys have
      demonstrated that the evoked activity in the deep cerebellar nuclei occurs too
      late to initiate the startle response (60) and electromyography of the
      postischemic myoclonus of rats corroborates this view (see Chapter 31) (20).
      However, the nearly complete loss of GABAergic terminals in the dorsolateral
      protuberance after Purkinje cell death would be expected to dramatically increase
      its tonic firing and the background excitation of the brain-stem structures that
      it innervates. The fastigial nucleus innervates a large number of autonomic and
      motor structures in the brainstem and diencephalon, including the ventrolateral
      nucleus of the thalamus and the gigantocellular reticular nucleus in the medulla-
      structures that have been implicated in human posthypoxic myoclonus (6, 7). We
      propose that the posthypoxic myoclonic jerk of rats is, at least in part, due to
      disinhibition of the fastigial nucleus produced by patterned Purkinje cell death
      in the vermis. The argument is as follows: the loss of GABAergic inhibition in
      the fastigial nucleus after ischemia leads to diaschisis of the motor thalamus
      and reticular formation which, in turn, is responsible for enhanced motor
      excitability and myoclonus. That the audiogenic myoclonus after global brain
      ischemia in the rat gradually resolves over a period of 2 to 3 weeks is
      consistent with this view, as restoration of background excitability after CNS
      damage in rats has been documented to occur within this time-frame (61). Our view
      brings together the physiologic finding that posthypoxic myoclonus appears to
      originate in the sensory-motor cortices and/or reticular formation with the
      consistent anatomical finding of Purkinje cell loss after ischemia, and explains
      the puzzle of Marsden's unique cases of myoclonus associated with coeliac disease
      (1). Moreover, our argument is consistent with findings both in rats (62, 63) and
      humans (64) that damage to the vermis impairs the long-term habituation of the
      startle reflex. It remains to be determined whether the pathologically enhanced
      startle responses after vermal damage resemble brain-stem reticular or cortical
      myoclonus at the electrophysiologic level of analysis. What is the purpose of the
      regional expression of aldolase C and EAAT4 in Purkinje cells? The close
      correspondence between the spatial distribution of aldolase C and the
      parasagittal anatomy of the cerebellum (48) has led to the view that aldolase C
      may help specify connectivity during development. While the present experiments
      do not address this issue, they underscore the fact that aldolase plays a
      fundamental role in metabolism. Because Purkinje cells have a repressed
      expression of aldolase A (31), whatever role the absence of aldolase C may play
      during development comes at the price of metabolic frailty later in adulthood.
      From another point of view, aldolase C and EAAT4 appear to confer upon Purkinje
      cells the ability to survive their own climbing fiber. Indeed, climbing fibers
      form a distributed synapse that synchronously releases glutamate (or aspartate)
      at all levels of the dendritic tree simultaneously (65, 66). Such synchronous
      activation triggers calcium influx throughout the Purkinje cell dendrites at a
      magnitude that is unparalleled in the nervous system (12), and, thus, places an
      extraordinarily high metabolic demand on the Purkinje cell. The apparently
      reduced level of aldolase in a subpopulation of Purkinje cells provides the
      condition for energy failure and death during anoxia so long as the climbing
      fibers are intact or when climbing fiber activation is pharmacologically enhanced
      under normoxic conditions, such as after ibogaine (53-56). Lastly, the argument
      that diaschisis produced by patterned cerebellar degeneration leads to thalamo
      cortical and reticular hyperexcitability agrees with C. David Marsden and his
      colleagues' bold demonstration of an inhibitory influence of cerebellar cortex on
      motor cortex in humans (67). Our anatomic data indicate that the spatially
      distinct zones of Purkinje cells, which are killed by global brain ischemia, may
      be the origin of such inhibition.

PMID- 11968460
TI  - Myoclonus in pallido-ponto-nigral degeneration.

PMID- 11968461
TI  - The Unified Myoclonus Rating Scale.

PMID- 11968462
TI  - The early history of paroxysmal dyskinesias.

PMID- 11968463
TI  - Classification of paroxysmal dyskinesias and ataxias.

PMID- 11968464
TI  - Secondary causes of paroxysmal dyskinesia.
AB  - PxD are sudden, episodic, involuntary movement disorders that may include any
      combination of dystonia, chorea, athetosis, or ballism. The majority of reported
      cases are familial or idiopathic; however, there have been several reports of
      secondary PxD. We report 20 new cases of secondary, non-psychogenic PxD, and
      review 130 cases reported in the literature. The results suggest that although
      PxD is a rare disorder, secondary forms may be more common than previously
      recognized, accounting for 26% of all cases in our series. Secondary cases are
      notable for their variability in age of onset, the presence of both kinesigenic
      and non-kinesigenic symptoms in some patients, the prevalence of sensory
      precipitants, and most importantly, the reversal of symptoms when the underlying
      etiology is treated in some patients. In addition to MS, other causes to be
      considered in patients presenting with PxD include cerebral vascular
      insufficiency and stroke, trauma, metabolic abnormalities, and CNS infections.
      Awareness of the association of these etiologies with secondary PxD will permit
      prompt diagnoses and appropriate interventions. Potential pathophysiologic
      mechanisms including loss of inhibition or primary neuronal hyperactivity are
      discussed. In addition, recent hypotheses regarding channelopathies in relation
      to PxD are presented.

PMID- 11968465
TI  - Myoclonus in Gaucher disease.

PMID- 11968466
TI  - Transient ischemic attacks and paroxysmal dyskinesias: an under-recognized
      association.

PMID- 11968467
TI  - Epilepsy and paroxysmal dyskinesia: co-occurrence and differential diagnosis.

PMID- 11968468
TI  - Animal models of paroxysmal dystonia.

PMID- 11968469
TI  - Molecular biology of episodic movement disorders.

PMID- 11968470
TI  - Genetics of episodic ataxia.

PMID- 11968471
TI  - Autosomal dominant nocturnal frontal lobe epilepsy.

PMID- 11968472
TI  - Clinical spectrum and genetics of Rolandic epilepsy.

PMID- 11968473
TI  - Toxin and drug-induced myoclonus.

PMID- 11968474
TI  - Myoclonus in parkinsonian disorders.

PMID- 11968475
TI  - The clinical challenge of posthypoxic myoclonus.

PMID- 11968476
TI  - Neurophysiology of cortical positive myoclonus.

PMID- 11968477
TI  - Neurophysiology of brainstem myoclonus.

PMID- 11968478
TI  - Overview of antibody phage-display technology and its applications.

PMID- 11968480
TI  - Antigen-driven stimulation of B-lymphocytes in vitro.

PMID- 11968479
TI  - Construction of polyclonal antibody libraries using phage display.

PMID- 11968481
TI  - The recovery of immunoglobulin sequences from single human B cells by clonal
      expansion.

PMID- 11968482
TI  - Panning of antibody phage-display libraries. Standard protocols.

PMID- 11968483
TI  - Selection of antibodies against biotinylated antigens.

PMID- 11968484
TI  - Isolation of anti-hapten specific antibody fragments from combinatorial
      libraries.

PMID- 11968485
TI  - Blocking immunodominant epitopes by competitive deselection.

PMID- 11968486
TI  - Rescue of a broader range of antibody specificities using an epitope-masking
      strategy.

PMID- 11968487
TI  - Screening of phage-expressed antibody libraries by capture lift.

PMID- 11968488
TI  - Antibody-guided selection using capture-sandwich ELISA.

PMID- 11968490
TI  - Isolation of human monoclonal antibodies using guided selection with mouse
      monoclonal antibodies.

PMID- 11968489
TI  - Proximity-guided (ProxiMol) antibody selection.

PMID- 11968491
TI  - Selecting antibodies to cell-surface antigens using magnetic sorting techniques.

PMID- 11968492
TI  - Isolation of human tumor-associated cell surface antigen-binding scFvs.

PMID- 11968493
TI  - Subtractive isolation of single-chain antibodies using tissue fragments.

PMID- 11968494
TI  - Selection of antibodies based on antibody kinetic binding properties.

PMID- 11968495
TI  - Selection of functional antibodies on the basis of valency.

PMID- 11968496
TI  - Two-step strategy for alteration of immunoglobulin specificity by in vitro
      mutagenesis.

PMID- 11968497
TI  - Targeting random mutations to hotspots in antibody variable domains for affinity
      improvement.

PMID- 11968498
TI  - Error-prone polymerase chain reaction for modification of scFvs.

PMID- 11968499
TI  - Use of Escherichia coli mutator cells to mature antibodies.

PMID- 11968500
TI  - Chain shuffling to modify properties of recombinant immunoglobulins.

PMID- 11968501
TI  - Generation of bispecific and tandem diabodies.

PMID- 11968502
TI  - High-level periplasmic expression and purification of scFvs.

PMID- 11968503
TI  - Periplasmic expression and purification of recombinant Fabs.

PMID- 11968504
TI  - Expression of antibody fragments in Pichia pastoris.

PMID- 11968505
TI  - Expression of VHH antibody fragments in Saccharomyces cerevisiae.

PMID- 11968506
TI  - Intrabodies. Targeting scFv expression to eukaryotic intracellular compartments.

PMID- 11968507
TI  - Expression of scFvs and scFv fusion proteins in eukaryotic cells.

PMID- 11968508
TI  - Expression of antibody Fab fragments and whole immunoglobulin in mammalian cells.

PMID- 11968509
TI  - Standard protocols for the construction of Fab libraries.

PMID- 11968511
TI  - Broadening the impact of antibody phage display technology. Amplification of
      immunoglobulin sequences from species other than humans or mice.

PMID- 11968510
TI  - Standard protocols for the construction of scFv libraries.

PMID- 11968512
TI  - Construction of large naive Fab libraries.

PMID- 11968513
TI  - The implications of terrorism for public health.

PMID- 11968514
TI  - Fear of crime and health in residential tower blocks. A case study in Liverpool,
      UK.
AB  - BACKGROUND: Though it is often assumed that fear of crime erodes mental health,
      research evidence is limited. Our study seeks to assess the relationship between
      these attributes in residents of the city of Liverpool. METHOD: Evidence is drawn
      from a sample survey of 407 adults living in 21 tower blocks. A number of social
      and psychosocial attributes linked with feelings of safety are compared with self
      reported health status using logistic and multiple regression techniques.
      Possible reciprocal relationships were investigated using two-stage least
      squares. RESULTS: Fear of crime in this sample is generally much lower in the
      home than in Britain as a whole and much higher out on the neighbouring streets
      at night, but there are sub-group variations. We find significant associations
      between fear of crime and health status. Feelings of safety when out alone after
      dark is the most consistent predictor of health status. Those feeling safe score
      significantly higher on all five dimensions of the SF-36 measure which cover
      mental and social well-being. Mental health is the strongest correlate and is
      probably a consequence rather than cause of feelings of safety. CONCLUSION: The
      evidence suggests elderly residents believe tower blocks provide safe
      accommodation. However, feelings of safety in these 'fortresses' do not generally
      extend to walking in neighbouring streets. Fear of crime erodes quality of life
      and is associated with poorer health.

PMID- 11968515
TI  - Some biological cardiovascular risk factors and diet in samples of the male
      population of Tallinn, Estonia in 1984/1985 and 1992/1993.
AB  - BACKGROUND: The role of diet in the development of atherosclerosis and coronary
      heart disease is well known from animal, clinical and epidemiological studies;
      the influence of dietary factors is realized through their impact on body mass,
      lipids and blood pressure. The aim of this investigation was to study the levels
      of some biological risk factors: blood pressure, total cholesterol, triglycerides
      and body mass, as well as nutrition, in the male population of Tallinn, the
      capital of Estonia, in 1984/1985 and 1992/1993 (the transition period). METHODS:
      Two independent random samples of the male population of Tallinn, aged 30 to 54,
      were examined in 1984/1985 (1,890 men) and in 1992/1993 (752 men). Standard
      epidemiological investigation methods were used; the diet was studied by the 24 h
      recall method. RESULTS: By the time of the second survey the age-adjusted mean
      values of systolic and diastolic blood pressure, body mass index and
      triglycerides, as well as the prevalence of arterial hypertension,
      hypercholesterolaemia and hypertriglyceridaemia were lower than at the first
      survey. These data were in accordance with the dietary pattern: lower energy,
      animal protein, fat, saturated fatty acids, cholesterol intake and higher
      consumption of vegetable protein and P/S ratio at the second survey. Taking into
      account close relationships between many nutrients and biological risk factors
      found previously, changes in the diet of the population, which occurred in
      postsocialist Estonia in the early 1990s, could be regarded as one of the reasons
      for the differences in the levels of these risk factors.

PMID- 11968516
TI  - How similar are the smoking and drinking habits of men and women in non-manual
      jobs?
AB  - BACKGROUND: Men used to be more likely to smoke and drink heavily than women.
      However, as social roles changed, so have gender differences in health-related
      behaviours. This paper explores whether gender differences in these behaviours
      persist or disappear among men and women occupying similar social roles: working
      in the same non-manual jobs in Britain. METHODS: Self-completion questionnaires
      were distributed to full-time employees in a bank (n = 2,139) and a university (n
      = 1,611). Response rates were 76% and 67% respectively. Respondents were asked
      whether they smoked currently. Men who reported drinking more than 21 units of
      alcohol, and women who reported drinking more than 14 units, in the last week
      were classed as 'heavy' drinkers. RESULTS: In both organizations there were no
      significant gender differences in smoking, but men were significantly more likely
      than women to report drinking 'heavily'. Employees in clerical jobs in the
      university were more than twice as likely as their more senior colleagues to
      smoke, but were significantly less likely to report drinking 'heavily' in both
      organizations. High masculinity scores among both men and women were associated
      with smoking and 'heavy' drinking. CONCLUSION: Men and women occupying similar
      social roles are equally likely to smoke but men are significantly more likely to
      drink 'heavily'. The relationship between paid work variables and these health
      behaviours are similar for both men and women. The association between high
      masculinity scores and health-damaging behaviours in both men and women points to
      the importance of considering gender role orientation, rather than just comparing
      men and women.

PMID- 11968517
TI  - Effect of parental social class, own education and social class on mortality
      among young men.
AB  - BACKGROUND: The aim of the study is to examine the effects of parental class, own
      education and social class on mortality by cause of death among young men.
      METHODS: The study is based on 1990 census records for 186,408 Finnish men, aged
      30-34 in 1990, linked with death records for 1991-95 (1530 deaths). RESULTS:
      Parental class was associated with all-cause (Index of Relative Dissimilarity
      (IRD) = 12%) and cause-specific mortality before adjustment for one's own social
      class and education. Adjustment reduced the IRD by 18-58%, depending on the cause
      of death, and caused mortality differences to disappear for causes other than
      cardiovascular diseases and those related to alcohol. The unadjusted variation in
      all-cause mortality by educational attainment (IRD = 33%) and by own class (IRD =
      38%) was greater than by parental class. Adjustment for parental class had only a
      minor effect on the variation by education and own class. Adjustment for own
      class reduced the IRD for education in all-cause mortality by 31%, in mortality
      from disease by 17%, and in mortality from external causes by 33%. For own class
      the reductions in the IRD obtained by adjustment for education were 36%, 46%, and
      33%, respectively. CONCLUSIONS: The effect of parental class on the mortality of
      young men is indirect and mainly mediated through its influence on education and
      social class. The effect of education on mortality is as strong as that of
      occupation-based social class. These variables are not interchangeable measures
      of socioeconomic status; they both should be taken into account in studies on
      inequalities in mortality.

PMID- 11968518
TI  - Correlates of wellbeing of spousal and children carers of disabled people over 65
      in Spain.
AB  - BACKGROUND: The aim of this study was to evaluate the associations between
      carer's wellbeing and stressors and to assess if these associations are different
      for spousal and children carers of disabled elderly. METHODS: Information was
      collected by home interviews of a population sample of carers (N = 195), who were
      providing assistance in activities of daily living to a community-dwelling
      population over 65. Associations between indicators of wellbeing (number of
      depressive symptoms, number of physical symptoms, self-perceived health and life
      satisfaction) and caring stressors were examined, controlling for carer's socio
      economic characteristics and health status. Hierarchical logistic regressions
      were used to fit the data. Religion and social support were included as resources
      and spousal and children differential associations were tested. RESULTS: The four
      indicators of wellbeing are moderately correlated, indicating a common underlying
      concept. Spousal carers have lower socio-economic status, poorer health and lower
      levels of wellbeing than children carers. However, children carers bear a
      significantly greater burden. In the multivariate analysis of the associations
      between wellbeing and stressors, the similarities between spouse and adult child
      carers are more striking than the differences. Emotional support was consistently
      associated with higher levels of wellbeing while the associations of religiosity
      and instrumental support with wellbeing did not reach statistical significance.
      CONCLUSION: As formal care services are being developed in Spain, their ability
      to work in a supportive way with family networks should be taken into account.
      Research should be carried out on patterns of formal care interventions that use
      the resources in the natural support network of the family.

PMID- 11968519
TI  - Changes in cardiovascular risk factors and health behaviours from 1992 to 1997 in
      the Republic of Karelia, Russia.
AB  - BACKGROUND: In Russia rapid changes have taken place both in total and chronic
      disease mortality during recent years. Little reliable information is available
      on the trends in conventional risk factors in Russia. METHODS: Chronic disease
      risk factors and health behaviours were studied in the Republic of Karelia,
      Russia in 1992 and 1997, in population surveys connected with the National
      FINRISK Study in Finland. Independent random population samples (n = 1000) of
      people aged between 25 and 64 years were drawn in both survey years. Surveys
      included a self-administered questionnaire, physical measurements and laboratory
      analyses. RESULTS: The levels of systolic blood pressure, total serum
      cholesterol, and high-density lipoprotein cholesterol decreased among both
      genders from 1992 to 1997, but the difference between the survey years was
      statistically significant only among women. Both self-reported alcohol
      consumption and serum gamma-glutamyl transferase levels increased significantly
      in both men and women. There was a significant shift in the type of fat used on
      bread and in cooking, from butter use to use of margarine and vegetable oil,
      among both genders. CONCLUSIONS: As a whole the risk factor levels in the
      Republic of Karelia are high. However, some slight improvement in risk profile
      was seen. Positive changes in dietary habits, such as change in the quality of
      fat and associated reduction in serum cholesterol levels may have contributed to
      the decline in cardiovascular disease mortality seen in Russia since 1995.
      However, since smoking and elevated blood pressure levels as well as alcohol
      consumption are still highly prevalent, there is a great need for effective
      interventions.

PMID- 11968520
TI  - Performance-based reimbursement in health care. Consequences for physicians' cost
      awareness and work environment.
AB  - BACKGROUND: The funding and structure of health care is currently undergoing
      major changes. The impact of such changes on professional behaviour and working
      conditions have not been widely studied in Europe. The two aims of this study
      were to prospectively assess the impact of performance-based reimbursement on
      physicians' attitudes and self-assessed professional behaviour, related to cost
      awareness, as well as their working conditions. METHOD: Physicians in Stockholm
      County Council (with a performance-based reimbursement system) and physicians in
      eleven Swedish councils without performance-based reimbursement were examined
      simultaneously in 1994. This was a cross-sectional questionnaire study. RESULT:
      The results show a heightened cost awareness among physicians in Stockholm but
      also greater discontent with working condition factors such as decision latitude,
      job satisfaction and personal well-being. CONCLUSION: These results suggest that
      in order to counteract physicians discontent as a result of altered structure and
      increased focus on performance-based reimbursement, the autonomy and influence of
      physicians over the work processes need to be considered.

PMID- 11968521
TI  - Primary care and genetic services. Health care in evolution.
AB  - The demand for services for predicting, diagnosing, and managing genetic diseases
      or diseases with a genetic component is likely to increase faster than the
      availability of services from medical geneticists and genetic counselors. Health
      care systems may also impose limitations on referrals to these specialists. If
      genetic problems are not to be missed and excessive referrals are to be avoided,
      non-geneticist practitioners will have to recognize when genetic problems should
      be considered, and initiate diagnosis and even management. Primary-care-centred
      systems offer the greatest potential for maximizing overall cost-effectiveness,
      by reducing the demand for specialty services not essential for improving health.
      But primary-care-centred systems may pose a risk of underdetection and
      undermanagement of genetic problems if practitioners are not actively supported
      by information and other educational networks. Several models for dealing with
      these challenges are presented, including algorithms that aid in recognizing
      genetic problems.

PMID- 11968522
TI  - Age-specific increases in health care costs.
AB  - BACKGROUND: The escalating costs of health care raise questions about
      demographic, epidemiological and technological determinants and future
      projections. The objectives of this work are to describe the age pattern of
      health care costs, to analyse the age-specific cost changes and to project future
      health care costs in an ageing population. METHODS: Comprehensive cost-of-illness
      data for the whole Dutch population in 1988 and 1994 are compared by age and type
      of care. National data on all hospital admissions, nursing days and clinical
      interventions for the period 1988-1994 is used to describe trends in hospital
      care. Population forecasts are used to project the age distribution of future
      health care costs. RESULTS: The distribution of health care costs per capita
      depends strongly on age. The growth rate of per capita costs increases by age for
      acute care but decreases by age for long-term care. Both combined cause an
      average annual growth rate of 4.6%, nearly constant with age. CONCLUSIONS: Ageing
      will result in increasing health care demands and costs. Secular trends in acute
      and long-term care indicate major shifts in costs from younger to older people
      and from long-term to acute care.

PMID- 11968523
TI  - Intercultural communication in general practice.
AB  - BACKGROUND: Little is known about the causes of problems in communication between
      health care professionals and ethnic-minority patients. Not only language
      difficulties, but also cultural differences may result in these problems. This
      study explores the influence of communication and patient beliefs about health
      (care) and disease on understanding and compliance of native-born and ethnic
      minority patients. METHODS: In this descriptive study seven general practices
      located in a multi-ethnic neighbourhood in Rotterdam participated. Eighty-seven
      parents who visited their GP with a child for a new health problem took part:
      more than 50% of them belonged to ethnic-minorities. The consultation between GP
      and patient was recorded on video and a few days after the consultation patients
      were interviewed at home. GPs filled out a short questionnaire immediately after
      the consultation. Patient beliefs and previous experiences with health care were
      measured by different questionnaires in the home interview. Communication was
      analysed using the Roter Interaction Analysis System based on the videos. Mutual
      understanding between GP and patient and therapy compliance was assessed by
      comparing GP's questionnaires with the home interview with the parents. RESULTS:
      In 33% of the consultations with ethnic-minority patients (versus 13% with native
      born patients) mutual understanding was poor. Different aspects of communication
      had no influence on mutual understanding. Problems in the relationship with the
      GP, as experienced by patients, showed a significant relation with mutual
      understanding. Consultations without mutual understanding more often ended in non
      compliance with the prescribed therapy. CONCLUSION: Ethnic-minority parents more
      often report problems in their relationship with the GP and they have different
      beliefs about health and health care from native-born parents. Good relationships
      between GP and patients are necessary for mutual understanding. Mutual
      understanding has a strong correlation with compliance. Mutual understanding and
      consequently compliance is more often poor in consultations with ethnic-minority
      parents than with native-born parents.

PMID- 11968524
TI  - Inpatient costs and paramilitary punishment beatings in northern Ireland.
AB  - BACKGROUND: Paramilitary punishment beatings are a common occurrence in Northern
      Ireland. Little is known about the costs such attacks impose on the health
      service. METHODS: Data was collected retrospectively on victims treated by
      Northern Ireland's regional specialist orthopaedics unit. Data related to all
      victims treated in the unit between January 1999 and May 2000. RESULTS: Average
      inpatient care costs were 2010 Pounds ($2914). There was no significant
      difference in these between patients who were shot and those who were beaten.
      CONCLUSION: Punishment beatings present a small but significant cost burden to
      the health service. A fuller understanding of them from a health care perspective
      is warranted.

PMID- 11968525
TI  - Has fallout from the Chernobyl accident caused childhood leukaemia in Europe? A
      commentary on the epidemiologic evidence.
AB  - BACKGROUND: According to radiation risk estimates uniformly adopted by various
      official organizations, exposure to Chernobyl fallout is unlikely to have caused
      any measurable health risk in central Europe. METHODS: A re-evaluation of ECLIS
      (European Childhood Leukaemia and Lymphoma Incidence Study), a large IARC
      coordinated project in the context of various published studies. RESULTS: ECLIS
      revealed a slightly higher leukaemia incidence in the most contaminated European
      regions, and an increasing trend with estimated cumulative excess radiation dose.
      The excess corresponds to 20 cases of childhood leukaemia in the study area up to
      1991. More recent evidence from Greece and Germany indicates significantly higher
      risks in the cohort of children in utero at the time of the initial fallout. In
      Greece, a positive trend was observed over three regions of increasing average
      fallout contamination. CONCLUSION: Chernobyl fallout could well have caused a
      small, but significant excess of childhood leukaemia cases in Europe. The
      etiologic mechanism might include an induction of chromosome aberrations in early
      pregnancy. Increased risks in the birth cohort exposed in utero correspond to 11
      excess cases in Greece and another 11.4 excess cases in Germany. Exposure
      misclassification and underascertainment of incident cases render post-Chernobyl
      risk estimates probably too low. If indeed Chernobyl fallout has caused childhood
      leukaemia cases in Europe, we would also expect an increased incidence for other
      childhood cancers and excess malignancies in adults as well as non-malignant
      diseases of all ages. Neither of these endpoints has as yet been systematically
      studied.

PMID- 11968526
TI  - Brain development affected by child sexual abuse.

PMID- 11968527
TI  - Chronic sorrow higher in HIV-positive women than men.

PMID- 11968529
TI  - Subdued lighting may encourage binge eating.

PMID- 11968528
TI  - Female stalkers as dangerous as male stalkers.

PMID- 11968530
TI  - Weight gain associated with antipsychotic agents.

PMID- 11968531
TI  - Professional boundaries. A matter of therapeutic integrity.
AB  - 1. Establishing and maintaining boundaries creates a relational space in which
      the patient and nurse are able to explore treatment issues within the safety of
      the therapeutic relationship. 2. The therapeutic relationship in founded on the
      basis of trust, respect, and appropriate use of power. Understanding the power
      differential within the nurse patient relationship is critical to the
      establishment and maintenance of professional boundaries. 3. Therapeutic
      integrity is rooted in knowledge, experience, and clinical judgment. As such,
      there are not always clearly demarcated answers to the tough questions posed by
      the dilemmas in practice. 4. Questions arising from practice challenge nurses to
      reflect on the meaning of boundaries in their personal and professional lives.

PMID- 11968532
TI  - When, catastrophe happens. Assessment and intervention after sudden traumatic
      death.
AB  - The goals of grief after sudden traumatic death is to acknowledge the loss,
      identify the changes the loss will have in the co-victim's life, and reinvest in
      life within the new structure. Although these goals seem simple, there is no
      definitive timeline for when these tasks will be engaged and completed by each of
      the family members. The pathway and time frame for each co-victim may differ.

PMID- 11968533
TI  - Review of shaken baby syndrome.
AB  - 1. Shaken baby syndrome can lead to substantial neuropsychological deficits that
      can alter children's normal developmental course. 2. Clinical acumen can be
      critical in identifying shaken baby syndrome and preventing further difficulties.
      3. Education and treatment for caregivers can be important in reducing the
      likelihood of shaken baby syndrome.

PMID- 11968534
TI  - Mentoring. Perceptions of the process and its significance.
AB  - My recommendations are to learn about the mentoring process, prepare for the
      role, and take advantage of the opportunity to mentor someone, or many people,
      throughout your professional lifetime. In the process, you will learn about your
      cognitive, affective, and behavioral competencies and gifts. Share them. Join me
      and other mentors in knowing that you have opened doors and contributed in more
      than the usual ways to both well and ill people, to both present and future
      leaders in nursing or other disciplines, in whatever role, and to society in
      general. Deepen your generativity.

PMID- 11968535
TI  - Integrating mental health care in primary health care.

PMID- 11968536
TI  - [Is low intensity ultrasound effective in treatment of disorders of fracture
      healing?].
AB  - This prospective consecutive study judges the effectiveness of pulsed low
      intensity ultrasound for treatment of boney healing disorders. 86 out of 100
      treatments were successful. Although in these 100 cases 64 delayed unions and 36
      nonunions were enrolled ultrasound therapy was performed as an alternative to the
      indicated operation in every case. Excluding ten cases of ununited fractures of
      the scaphoid no additional therapy was performed in any case. Stratifying the
      data no significant differences in healing rate and treatment time were observed
      between delayed unions and non-unions and between atrophic and hypertrophic
      healing disorders. Judging the healing rate of 86% one has to take into
      consideration that according to our in- and excluding criteria we had a
      preselected sample of patients. Nevertheless the effectiveness of pulsed low
      intensity ultrasound for treatment of disorders of the fracture repair process is
      evident.

PMID- 11968537
TI  - [Minimal invasive treatment of massively dislocated radial neck fractures in
      children by percutaneous joystick reposition and Prevot nailing].
AB  - Undisplaced fractures of the proximal radius can generally be treated
      conservatively with good results. In children, spontaneous correction of some
      angular deformities can be expected during growth. Nevertheless, more severely
      displaced fracture types may require reduction in children, too. Open reduction
      and internal fracture fixation have shown to lead to a loss in range of motion
      frequently. A technique of percutaneous fracture reduction is demonstrated that
      can provide good results in cases when closed techniques have failed. A Kirschner
      wire is used to manipulate the fracture fragments percutaneously, which can often
      prevent open techniques. An additionally performed elastic-stable intramedullary
      nailing can add to an effective stabilisation and encourage to early
      physiotherapy.

PMID- 11968538
TI  - [Mantel transplant for defect reconstruction after resection of malignant bone
      tumors of the lower extremity].
AB  - We treated 11 patients with primary sarcoma and 1 patient with enchondroma of the
      femur or tibia. Bridging the osseus defect we used an intercalary allograft shell
      and contralateral fibula as described by Capanna et al. [7]. The median bone
      defect after resection of the tumor was 15.7 (9.0-28.5) cm, average follow up was
      29.2 (13-56) month. Anastomosis of the autologous fibula was successful in 8
      cases. There were 3 cases necessitating later amputation. The other cases showed
      good clinical (Enneking-score) and radiological (ISOLS-score) results. These
      results indicate the described technique as a suitable method for defect
      reconstruction with good functional outcome.

PMID- 11968539
TI  - [Long-term outcomes after using porous hydroxyapatite ceramics (Endobon) for
      surgical management of fractures of the head of the tibia].
AB  - Endobon is a porous hydroxyapatite ceramic which has been used as a bone
      replacement substitute since 1989. Currently there are no data available
      reflecting long-term effects of Endobon in human bone grafting. In order to
      assess such effects 35 patients with fractures of the proximal tibia were studied
      retrospectively over a period up to 91 months. The metaphyseal defects were
      filled by Endobon and fractures were stabilized by internal plate fixation
      subsequently. A secondary loss of reduction due to mechanical failure of the bone
      replacement material did not occur even after removal of metal implants. No
      histological signs of resorption or degradation could be found 18 months after
      application. Our data show that Endobon provides good mechanical properties
      during a long term follow-up and can be recommended as a suitable therapeutic
      option versus cancellous bone graft.

PMID- 11968540
TI  - [Basic principles and surgical technique of tibio-fibula-plasty in cartilage-bone
      transplantation].
AB  - BACKGROUND: Within the last few years autologous cartilage-bone-grafting is
      becoming an established standardized procedure in joint surgery. One significant
      disadvantage of this technique is the harvesting of the bone plugs from the
      weight-bearing area of the knee joint. PURPOSE: The tibiofibular articulation is
      located close to the knee joint that is operated on. This articulation is covered
      with cartilage. The purpose of this study was to evaluate the question, whether
      this joint is suitable as a donor site for bone-cartilage transplants. MATERIAL
      AND METHODS: Favourable approaches and committing of anatomical landmarks were
      investigated on 44 fixed tibiofibular joints. In knee extension, the shortest
      distance between the joint cleft and common fibular nerve was measured. The
      cartilage thickness and histology of both the fibular and tibial joint surface
      were documented. The developed surgical approach was evaluated in patients.
      RESULTS: Histological and immunohistochemical examination showed hyaline
      cartilage and type II collagen. The average cartilage thickness was 1.9 +/- 0.29
      mm (minimum: 1.5 mm; maximum: 2.6 mm). The peroneal nerve showed an average
      distance to the tibiofibular joint of 24 mm (minimum: 12 mm; maximum: 30 mm).
      Different surgical procedures are possible and clinical relevant. CLINICAL
      RELEVANCE: The tibiofibular joint contains cartilage, which may be a reasonable
      donor site even for the elderly patient. Harvesting the graft from this area may
      avoid iatrogenic damaging of intraarticular weight bearing cartilage of the knee
      joint.

PMID- 11968541
TI  - [Possibilities for improving fatigue properties of interlocking screws of solid
      tibial nails. A mathematical model with practical conclusions].
AB  - One major problem using small diameter nails in the treatment of tibial fractures
      is the high rate of fatigue fractures of the locking screws. The objective of
      this study was to develop a mathematical model for analysis of the stress
      concentration factor as well as edge fibre stress. This would allow an analysis
      of the stress peaks caused by the thread of the screw as well as showing ways to
      increase the fatigue limits of the screws. The main consideration was the fact
      that a thread can be calculated like a relief notch used in theory of strength to
      relieve the strain on building materials. The transformation from one notch to
      multiple notches obviously reduces the stress concentration factor. To improve
      the fatigue limit of locking screws one has to modify the stress concentration
      factor or the edge fibre stress on the implant. Absence of a thread at the
      location where the screw contacts the nail's aperture (where the main load is
      transmitted to the screw and where the screw therefore usually tends to break)
      may double the fatigue strength and fatigue limit by avoiding the negative notch
      effect of the screw's thread. If this option is not possible one has to consider
      that the optimal threaded screw should have a minimal edge distance, a high notch
      radius and a minimal edge depth.

PMID- 11968542
TI  - [Diagnosis and therapy of bone metastases].

PMID- 11968543
TI  - [Treatment of spinal fracture in ankylosing spondylitis].
AB  - Clinical guidelines for the treatment of vertebral fractures associated with
      ankylosing spondylitis are derived from case reports and a review of literature.
      The coincidence of paravertebral calcifications and fracture formations leads to
      problems in the establishment of a proper initial diagnosis. Therefore computed
      tomography and magnetic resonance imaging have to be employed to define the
      extent of fracture and the presence of spinal lesions. As a rule vertebral
      fractures based upon spondylitic alterations are extremely unstable and tend to
      secondary dislocation with a high risk of spinal cord injuries. Operative
      osteosynthesis is the method of choice in the fracture treatment. A successful
      stabilization requires an extended spondylodesis comprising at least five
      vertebral segments by a dorsal or a combined ventral instrumentation.

PMID- 11968544
TI  - [Total endoprosthesis of the upper ankle joint after post-traumatic arthrosis].
AB  - In 1997 six patients with posttraumatic ankle arthritis aged 54 (45-71) years
      were treated with a LINK S.T.A.R. ankle prothesis. The average follow up was 29
      (21-36) months. Results were evaluated according to the ankle score of H. Kofoed
      [7]. Two patients had an excellent outcome and 1 patient had a fair result. In
      three patients secondary arthrodesis had to be performed, due to loosening of the
      implant. Based on our experiences we cannot recommend this implant for patients
      with posttraumatic arthritis at this time.

PMID- 11968545
TI  - [Cervical spine injuries in stable lower cervical spine with spinal stenosis].
AB  - The aim of the study was to investigate the neurological outcome of spinal cord
      injuries in the traumatized cervical spine with a stenosis of the spinal
      medullary canal. From 1992 to 1999 we treated 145 spinal cord injuries and/or
      injuries with an unstable cervical spine, 138 were treated operatively, in 7
      patients we found an injury of the spinal cord with a stable cervical spine and a
      stenosis of the spinal medullary canal. The radiological diagnostics consisted of
      anterioposterior X-rays of the cervical spine, an X-ray view of the dens axis and
      a stress roentgenogramm in extension and flection. An MRI was performed within
      the first 12 hours after the accident. The stenosis of the spinal medullary canal
      was evaluated by the quotient of the mid-sagittal diameter of the spinal
      medullary canal as well as the vertebral body (Torg-quotient) and ranged from 0.5
      to 0.8. Pathological changed values were found in 4 patients within 2 segments
      and in 3 patients within 3 segments. In the T2-turbospin echo sequence
      hyperintense lesions of the spinal cord, accordingly to an edema were found in 6
      patients. The neurological evaluation was performed according to the "Standard
      Neurological Classification of Spinal Cord Injuries". Treatment of these 7
      patients was performed conservatively, consisting of NSAR as well as Methyl
      Prednisolon according to the pattern of NASCIS-II and III. The follow-up was
      performed after 12 to 18 months. We evaluated the X-rays in anterioposterior and
      lateral view, stress roentgenogramms and neurological status. Radiological
      findings showed stable conditions of the cervical spine with block vertebras and
      increased osteophytes. The neurological outcome was evaluated according to the
      "Motor-Score" and showed an improvement from 8 to 63 points within 13 months in
      one case. In 6 cases, the average "Motor-Score" of 78 increased to 100 points
      within 2 to 5 months after injury. Most defunctionalization symptoms were found
      in the upper extremities. Disturbances in fine motor movement were unable to be
      examined with the "Motor-Score". We can conclude that spinal cord injuries in
      stable cervical spines with stenosis of the spinal medullary canal can be treated
      conservatively with a good outcome. A regression of the neurological deficiency
      can be expected within 2 to 5 months, but even after one year, deficiency
      regression is possible.

PMID- 11968546
TI  - [Medial femoral neck fracture. Controversies in treatment].
AB  - The treatment of the medial femoral neck fracture remains controversial until
      today. The goal of this paper is therefore, based on the literature, to show
      guidelines for optimal treatment: conservative treatment vs. operation,
      osteosynthesis vs. prosthesis, timing for osteosynthesis, open vs. closed
      reduction, choice of implant for osteosynthesis, postoperative treatment (weight
      bearing vs. non weight bearing), Pauwels-Osteotomy vs. prosthesis in cases op
      pseudarthrosis, femoral head prosthesis vs. total hip arthroplasty, bipolar vs.
      monopolar femoral head prosthesis, choice of classification. Further we want to
      point out which statements are evidence based and where we need further
      investigation.

PMID- 11968547
TI  - [Tissue engineering of tendon and ligament tissue].

PMID- 11968548
TI  - [Tissue engineering of tendons and ligaments. A new challenge].
AB  - Injuries to ligaments and tendons heal by formation of inferior repair tissue.
      This may result in severe joint dysfunction. Because of an increased occurrence
      of sports-related injuries, musculoskeletal disorders may become one of the major
      burden of health care. Tissue engineering offers the potential to improve the
      quality of ligament and tendon tissues during the healing process and may provide
      a more effective approach to the treatment of injuries to ligaments and tendons
      than traditional methods. Application of growth factors, gene transfer
      techniques, cell therapy and cell-matrix composites have shown to affect the
      process of ligament and tendon healing. The benefits of using mesenchymal stem
      cells on a three dimensional biological matrix have been shown recently. Tissue
      engineering will also include mechanical manipulation of tissue environments to
      accelerate cell differentiation and to improve matrix formation. Fibroblast
      seeded polymer scaffolds could be useful in ligament and tendon replacement in
      which autogenous fibroblasts would be obtained through biopsy, cultured and
      seeded onto a scaffold.

PMID- 11968549
TI  - [Dislocated supracondylar humerus fracture in the child. Surgical technique and
      outcome with dorsal approach].
AB  - Anatomical reduction and stabilization of displaced supracondylar humeral
      fractures in children is necessary to obtain good results. For most cases
      percutaneous crossed pinning is recommended. Sometimes open reduction is
      necessary but even in these cases neurological complications and varus
      deformities have been reported. So the technique of open pinning was modified.
      From 1995 to 1998 22 children were treated by a dorsolateral approach. The
      fracture was stabilized by crossed pinning: The proximal K-wire is drilled 10
      degrees ascending to the dorsal humerus through the medial pillar into the
      ventral part of the medial epicondyle, after shortening it is not bent. The
      distal K-wire stabilizes the lateral pillar, after shortening its end is bent
      down. Immobilization for 3-4 weeks, mobilization is done by the patient. The
      implants are removed 2 weeks later. The follow up in 21 out of 22 patients (8-57
      months, mean 35 months) according to Flynn's criteria showed 16 excellent, 4 good
      and 1 fair result. The fair result was due to valgus deformity. One patient has
      been reoperated due to displacement of K-wire. Neither iatrogenic nerve lesions
      nor varus deformities nor infections did occur. The dorsolateral approach
      combined with the above mentioned technique of pinning shows excellent and good
      results.

PMID- 11968550
TI  - [What prognostic factors correlate with activities of daily living (Barthel
      Index) 1 year after para-articular hip fracture? A prospective observational
      study].
AB  - The aim of this prospective study was to identify prognostic factors predicting
      post-operative outcome in patients one year after their hip fracture. METHODS:
      From October 1996 until September 1997 all patients (n = 98) treated for a hip
      fracture in our hospital were prospectively included into the study. Follow up
      was performed at three, six and twelve months after the injury. The main outcome
      variable was the activity of daily living measured by the Barthel-Index. An
      univariate analysis of the variables age, gender, ASA-classification, type of
      fracture and treatment, length of stay and rehabilitation was performed and all
      these variables were correlated with the Barthel-Index. A multiple logistic
      regression was performed for identification of prognostic factors predicting
      outcome. RESULTS: The one year lethality was 33% (n = 31). All patients younger
      than 75 years reached their preoperative activity level at one year follow up.
      Patients with age of 75 years or more experienced a reduction of their activities
      of daily living of 20%. The ADL-differences of both groups at the follow up after
      3, 6 and 12 months showed a significant p-value (p < 0.001). The ADL-differences
      between the group of patients with or without a transfer to a specialized
      rehabilitation center were not significant. The multivariate analysis showed that
      the preoperative use of the Barthel-Index was the best prognostic factor for
      outcome until one year after the injury. CONCLUSION: The preoperative Barthel
      Index should be seriously considered for therapeutic decision making in patients
      with hip fractures.

PMID- 11968551
TI  - [Percutaneous cementing techniques. New possibilities in therapy of
      osteoporosis].

PMID- 11968552
TI  - [Using prostaglandin E1 in microvascular reconstruction of the upper extremity
      after acute trauma].
AB  - The operative treatment of hand and upper extremity trauma with injury of main
      vessels becomes a daily standard work in trauma and microsurgical replantation
      centers. The techniques of vessel and soft tissue reconstruction are well known.
      The outcome of the replantation depends on various factors. Main influences are
      the intraoperative status of the vessel wall and the unobstructed flow in the
      vessel after the operation. Another factor for successful replantation is the
      homeostasis of the patient. It can be influenced by many drugs which are applied
      according to a replantation schema. Aim of this therapy is the correction of the
      rheologic properties of a patient. In a patient group of 25 treated with
      Prostaglandin E1 (Prostavasin) we observed better wound healing with a 80% rate
      of successful replantation and microvascular vessel reconstruction.

PMID- 11968553
TI  - [In situ connection of a hollow intramedullary nail to the stem of a knee
      prosthesis in periprosthetic fracture].
AB  - Periprosthetic fractures often reveal problems and complications because of poor
      bone quality. A case report is presented, in which a hollow intramedullary nail
      was connected, in situ, with the stem of a knee prosthesis (Blauth knee). Two
      plate osteosyntheses had previously failed. As ultima ratio, a hollow
      intramedullary nail was placed antegrade on the stem of the knee prosthesis.
      Afterwards excellent callus formation developed and resulted in consolidation.

PMID- 11968554
TI  - [Percutaneous cementing techniques in treatment of osteoporotic spinal
      sintering].
AB  - During the last years minimal-invasive augmentation techniques of vertebral
      bodies have been established to stabilize painful height losses. A vertebroplasty
      fills the vertebral body with cement, whereas a kyphoplasty intends to achieve a
      reduction of kyphosis prior to cementing. The present review describes both
      techniques and summarizes in vivo and in vitro experiences.

PMID- 11968555
TI  - [Primary strength of conventional and alternative suture techniques of the
      rotator cuff. A biomechanical study].
AB  - The aim of this biomechanical study was to evaluate rotator cuff repair strength
      using different suture anchor techniques compared to conventional repair, taking
      into consideration the native strength of the supraspinatus tendon. Therefore, a
      defined defect of the supraspinatus was created in 50 freshly frozen cadaver
      specimen (group size n = 10; median age at death: 56 years). Five methods were
      employed for cuff repair: standard transosseous suture, modified transosseous
      suture with patch augmentation and three suture anchors (Acufex Wedge TAG, Acufex
      Rod TAG und Mitek GII). The maximum tensile load of the five techniques was:
      standard transosseous suture, 410 N; modified transosseous suture, 552 N; Wedge
      TAG, 207 N; Rod TAG, 217 N; Mitek GII, 186 N. The difference between the suture
      anchor and standard techniques were highly significant (P < 0.001). In this
      series, the Mitek Gll anchor showed the lowest anchor dislocation rate at 3% (n =
      1). The Wedge TAG system had a dislocation rate of 27% (n = 8) and the Rod TAG
      system 43% (n = 13). Suture anchor techniques revealed about 20%, the standard
      technique 34% and its modification 60% of the hypothetically calculated native
      tendon strength. Compared to conventional transosseous suture techniques, the use
      of the suture anchors tested in this series does not significantly increase the
      primary fixation strength of rotator cuff repair. The metallic implant with two
      barbs (Mitek GII) seems to be superior to the polyacetal anchors when inserted
      into the spongiform bone of the greater tubercle. The considerably weaker repair
      strength needs to be taken into consideration in postoperative patient
      rehabilitation, especially after the use of suture anchors.

PMID- 11968556
TI  - [Influence of implant position of a hip prosthesis on alignment exemplified by
      the CLS shaft].
AB  - We performed a clinical and radiological analysis to evaluate the significance of
      the stem position of cementless CLS components with respect to function and
      survival. We used patient material from a multi-center study of 3,732 CLS stems
      with a mean follow-up of 43 months (range: 12-142 months). The clinical outcome
      was assessed using Merle D'Aubigne Scores and stem alignment was determined as
      the deviation of the longitudinal stem axis from the longitudinal femur axis. We
      found no correlation between stem alignment and function, survival, implant
      migration or periprosthetic radiolucent lines. In patients with rheumatoid
      arthritis and hip ankylosis the neutral stem position was less often achieved
      than in patients with other diagnoses. The results of our study cast doubt on
      whether the varus position of the femoral component of cementless tapered CLS
      type stem designs is as critical as in cemented total hip arthroplasty.

PMID- 11968557
TI  - [Effect of a sensorimotor training program on patients with subacromial pain
      syndrome].
AB  - The purpose of the present study was to evaluate the effectiveness of a special
      sensorimotor exercise rehabilitation program on shoulder function. In a
      prospective intervention study we evaluated 32 patients with subacromial pain
      syndrome, all of whom took part in a conservative rehabilitation program. No
      patient had surgery on the shoulder involved prior to the study. All patients
      performed a standardised sensorimotor training for the glenohumeral joint, which
      involved, in particular, the glenohumeral and scapulothoracal stabilisers. In
      this rehabilitation program special proprioceptive exercise tools (body-blade,
      BOING) were used as well as Tai Chi and aquatic gymnastics. The entire program
      lasted 4 weeks and was performed and supervised by the same physiotherapist.
      Prior to and after the program all patients underwent a standardised series of
      tests. These included the Constant- and the UCLA-Score tests and sensorimotor
      functions with an angle reproduction test, a threshold to motion test as well as
      isometric strength testing with a Cybex unit. Prior to the rehabilitation program
      all subjects showed decreased proprioceptive capabilities. This was particularly
      evident in the threshold to motion test. After 4 weeks of rehabilitation,
      significant increases in the Constant- and UCLA-Score tests were found. The
      sensorimotor test also showed an increased proprioceptive capability especially
      in the threshold to motion test. The angle reproduction test showed only moderate
      improvement, whereas the isokinetic strength test showed no improvement at all.
      The present study shows that patients with subacromial pathology suffer from a
      proprioceptive deficit which can be improved by a special rehabilitation program
      within only 4 weeks.

PMID- 11968558
TI  - [What influence do size and placement of patella resurfacing have on knee
      endoprosthesis?].
AB  - The aim of this study was to document the changes in retropatellar pressure,
      contact area and forces due to different sizes and placement of the patella
      resurfacing in knee arthroplasty. Six cadaver specimens (after Thiel fixation)
      were examined after the implantation of the total knee arthroplasty Genesis I.
      The patella sizes "small" and "medium" were placed as the "onlay" version,
      centered as well as off-centered by 0.4 cm in all four directions. Pressure and
      area measurements were done with Fuji pressure measuring film, which was placed
      between the patellar fascia of the femur and the patella in a defined position.
      The pressure was measured by applying a predetermined force for 5 s. The
      examinations were done with 60 degrees knee flexion and a force of 280 N. In our
      results there were no significant differences between, patella sizes. No
      significant differences for the medial, distal and proximal placement were found
      for the small patella. The lateral placement led to a significant decrease in the
      contact area (P = 0.0277), maximum pressure (P = 0.0422) and force (P = 0.0277).
      The average pressure did not change significantly (P = 0.1159). For the medium
      size patella there were no significant differences for medial or distal
      placement. The comparison of lateral and central placement revealed a significant
      decrease in the contact area (P = 0.0446). Comparing distal and proximal
      positioning, a significant increase in contact area and significant decrease in
      force were found (P = 0.0277 and P = 0.0277 respectively). In conclusion, the
      choice of small or medium patella resurfacing does not seem to have a significant
      influence. In comparison to the results without patella implants, the
      implantation of the small patella caused a significant decrease in the
      retropatellar contact area (P = 0.03) and force (P = 0.03). Average and maximum
      pressure did not change significantly (P = 0.6 and P = 0.35) even though pressure
      increased slightly. For the medium size, maximum pressure (P = 0.03) increased
      significantly and force decreased significantly (P = 0.0277) whereas contact area
      and average pressure increased slightly. The results of the different placements
      of the patella implant do not support the recommendation for a medial shift.
      However, at least the lateralized implantation led to a reduction of contact area
      and force as well as to a slight increase of pressure which is considered as
      unfavorable.

PMID- 11968559
TI  - [Post-traumatic lesion of the brachial plexus. Classification, diagnosis,
      documentation and therapy].

PMID- 11968560
TI  - [Traumatic jejunal entrapment in a patient with Bechterew disease].
AB  - We report an unusual case of incarceration of small bowel between the 4th and 5th
      lumbar vertebrae in a patient with rheumatoid spondylitis. Incarceration of the
      loop of jejunum within the fracture or between dislocated lumbar vertebrae is an
      uncommon entity. The cases of traumatic jejunal entrapment have been previously
      reported in the literature [1, 2, 3, 4, 5, 6, 7, 8, 9, 11]: 2 cases occurred in
      adults and 8 in children. There has been no report on this injury in patients
      with rheumatoid spondylitis (Bechterew arthritis).

PMID- 11968561
TI  - [Intramedullary nail placement with percutaneous Kirschner wires. Illustration of
      method and clinical examples].
AB  - Unreamed nailing is an established method for internal fixation of femoral und
      tibial shaft fractures. The interlocking technique allows the stabilization of
      metaphyseal fractures, too, but the risk of malalignment increases. The "palisade
      method" presented here allows the precise positioning of the nail in the marrow
      cavity and works as a tool for successful minimally invasive nailing in the
      meta/epiphyseal region. The method is easy to use and suited particularly in
      combination with the UFN and UTN, but is in principal applicable to other nails,
      too. In contrast to the "Poller Screw" method developed by Krettek et al., no
      biomechanical augmentation of the osteosynthesis remains.

PMID- 11968562
TI  - [Allogenic transplantation of femoral condyle after traumatic injury].
AB  - A 21-year-old man experienced an open knee injury with a subtotal loss of the
      medial part of the distal femur. After an initial debridement of the wound we
      performed 48 hours post injury an allogeneic transplantation of the condyle of
      the femur. The wound healed by first intention and no signs of rejection were
      noted. The bone transplant hadn't been treated specifically prior to the
      transplantation and the patient didn't receive any immunodepressive drugs. 18
      months later, the patient is able to flex the knee joint up to 120 degrees and to
      extend it completely. The overall result is excellent.

PMID- 11968564
TI  - [Adverse effects if smoking on healing of bones and soft tissues].
AB  - This article reviews the current body of knowledge on the adverse effects of
      smoking on soft-tissue and bone healing, with emphasis on tibial fractures in
      combination with severe soft-tissue injury. The pathophysiological effects are
      multidimensional, including arteriolar vasoconstriction, cellular hypoxia,
      demineralisation of bone, and delayed revascularisation. Several animal and
      clinical studies have been published about the negative effects of smoking on
      bone metabolism and fracture healing. These studies show that smokers have a
      significantly longer time to clinical union than non-smokers and a higher
      incidence of non-union. The negative effects of smoking gained increased interest
      among plastic and microvascular surgeons, because smokers have been shown to
      suffer higher rates of flap failure, tissue necrosis, and haematoma formation.
      Especially smokers presenting with an open tibial fracture will suffer the
      negative effects of their smoking behaviour, because these fractures are
      inextricably bound up with soft-tissue injury. Their fractures will need a
      significantly longer time to heal than in non-smokers, and will have a higher
      incidence of non-union. If microvascular surgery is to be performed, persistent
      smoking significantly increases the rate of postoperative complications, with
      wound infection, partial flap necrosis, and skin graft loss being more common.
      Cessation of smoking has both short- and long-term beneficial effects. Nowadays,
      there is strong evidence to be very insistent that patients presenting with a
      (open) tibial fracture should refrain from smoking immediately to promote bone
      healing and to lower the complication rate. In case of elective reconstructive
      procedures, patients should refrain from smoking at least 4 weeks before surgery.
      In both situations, cessation should continue during the full rehabilitation
      period.

PMID- 11968565
TI  - [Postoperative radial paralysis. Fate or negligence, conservative wait or
      revision?].
AB  - Radial nerve palsy is a rather frequent complication caused by an accident as
      well as by surgery of the humerus. As a primary, i.e., accidental lesion, its
      incidence as stated in the literature is up to 30%, primarily fractures in the
      distal diaphyseal half. Secondary, i.e., surgically induced, nerve lesions
      surprisingly are reported with a similar frequency, though recently the incidence
      only approaches some 3%. Experts continue to argue over the timing for operative
      revision. Many authors rely on spontaneous recovery of the nerve as maintained by
      L. Boehler in the early 1960s, but this theory was rendered obsolete by the
      technical achievements of microsurgery and the patients' economic constraints.
      Other authors are afraid of accidentally damaging the nerve by revision surgery.
      The stand we take in this controversy is instant revision surgery both for
      accidental lesions as well as uncompromisingly for those incurred during surgery
      when the surgeon had not explored the nerve far enough to preserve it during the
      operation. Three exemplary cases are reported, one of them submitted for an
      expert's opinion because of an alleged mistake on the part of the doctor.
      Forensic responsibility has to match actual indication principles and the
      specific technique applied.

PMID- 11968566
TI  - [Proximal interlocking of humeral intramedullary nails and risk of axillary nerve
      injury].
AB  - QUESTION: Possible injuries to the axillary nerve are criticised in antegrade and
      retrograde endomedullary nailing of the humeral shaft during proximal
      interlocking. Clinical experience seems not to support the theory of a high risk
      of nerve injury. The real risk although remains unknown under anatomical
      morphological aspects. MATERIAL AND METHODS: Eight complete human cadaveric
      shoulder-arm regions with original soft-tissue coverage had been used. Four times
      the unreamed humeral nail (UHN) had been inserted retrograde, and four times
      antegrade, distributed in each pair. Antegrade interlocking was performed after
      skin incision and spreading of soft tissues through the aiming devices. This
      involved one oblique bolt from lateral to medial. Retrograde proximal
      interlocking was performed under image intensifier. This involved triple
      interlocking, once dorso-ventrally and twice latero-medially. The incision paths
      have been marked. After preparation of the nerve stem in the lateral axillary
      portal the different branches have been searched and exposed. The spatial
      relations of bolts and nerve branches have been measured and the insertion path
      of the bolts has been revised, finally lesions of nerve structures have been
      documented. RESULTS: We found the latero-medially inserted bolt heads of the
      retrograde approach and the oblique bolt head of the antegrade approach being
      placed in a safe distance from the medio-dorsally positioned stem of the axillary
      nerve. On the other hand the dorsoventrally inserted bolt head (retrograde
      approach) showed in most cases a very tight relation to the nerve stem. Exploring
      the axillary nerve and its branches showed in no case a direct nerve lesion.
      CONCLUSIONS: We suggest to perform only a sharp cutaneous incision and then to
      prepare the muscle only by careful spreading until touching bone, with tissue
      retraction during drilling. In retrograde nailing the dorso-ventral bolt should
      only be used in extreme proximal fractures.

PMID- 11968567
TI  - Trends in twin and triplet births: 1980-97.
AB  - This report presents data from U.S. birth certificates on the numbers and rates
      of twin and triplet and other higher order multiple births for 1980-97. Over the
      study period, the number of twin births rose 52 percent (from 68,339 to 104,137)
      and triplet and other higher order multiple births (heretofore referred to as
      "triplet/+") climbed 404 percent (from 1,337 to 6,737 births). Comparable but
      less pronounced rises were observed in twin and triplet/+ birth rates. Growth in
      twin and triplet/+ birth rates was most marked among women aged 30 years and
      over. Between 1980-82 and 1995-97, the twin rate rose 63 percent for women aged
      40-44 years, and soared nearly 1,000 percent for women 45-49 years. (As one
      result, there were more twins born to women 45-49 years of age in 1997, than
      during the entire decade of the 1980's.) The triplet/+ birth rate rose nearly 400
      percent for women in their thirties and exploded by more than 1,000 percent for
      women in their forties. The extraordinary rise in multiple births resulted in a
      shift in age-specific patterns, and the highest twin and triplet/+ birth rates
      now are for women 45-49 years of age. Historical differences in twinning rates
      between non-Hispanic white and black mothers have been largely eliminated (28.8
      per 1,000 non-Hispanic white compared with 30.0 for black women). Non-Hispanic
      white women were more than twice as likely as non-Hispanic black or Hispanic
      women to have a triplet/+ birth. Rates of low birthweight, very low birthweight,
      and infant mortality were 4 to 33 times higher for twins and triplet/+ compared
      with singleton births. The risk for these adverse outcomes was lowest for twins
      and triplet/+ born to women 35-44 years of age. Twin birth rates for
      Massachusetts and Connecticut were at least 25 percent higher than the U.S. rate;
      triplet/+ rates for Nebraska and New Jersey were twice the national level.

PMID- 11968568
TI  - Case of the month. Diagnostic pearls.

PMID- 11968569
TI  - Attack on the Pentagon. The initial fire & EMS response.

PMID- 11968570
TI  - Silent assassin. Managing exposure incidents of unknown origin.

PMID- 11968571
TI  - Stay on the air. The importance of maintaining communication at mass casualty
      incidents.

PMID- 11968572
TI  - MCI resource guide 2002. MCI & weapons of mass destruction equipment & supplies
      at your fingertips.

PMID- 11968573
TI  - Unmask thoracic injuries. 3 cases to help you zero in on severe chest injuries in
      the field.

PMID- 11968575
TI  - [The truth about devitalization].

PMID- 11968574
TI  - Glucose gone wild, Part 2. Common diabetic emergencies: the EMS assessment &
      treatment of diabetic ketoacidosis & hyperglycemic-hyperosmolar nonketotic
      syndrome.

PMID- 11968576
TI  - [TT virus infection in liver transplant recipients with cryptogennic cirrhosis].
AB  - The possible causative role of novel TT virus in liver diseases has been
      intensively studied in regarding its hepatotrophy, ability to cause persistent
      infection and worldwide prevalence. The aim of this study was to estimate the
      prevalence as well as the clinical importance of TTV in a normal healthy
      population group in the Czech Republic and in a group of liver transplant
      recipients diagnosed with cryptogenic cirrhosis. Polymerase chain reaction (PCR)
      detected the DNA of TT virus in 68% (13/19) of samples isolated from peripheral
      blood leukocytes and in 21% (4/19) of plasma samples in the liver transplant
      group. The viral DNA was detected only in 11.8% (4/34) of leukocytes and in no
      plasma sample from the healthy population control group. All patients included in
      this study had good liver function and had no complications during the
      postoperative period. The prevalence of TTV DNA detection in healthy control
      group in Czech republic is similar to the rates reported in European and North
      American countries. Significant difference was proved between the prevalences of
      TTV in the groups of healthy controls and liver transplant recipients with
      cryptogenic cirrhosis. However, no association of TTV infection with possible
      postoperative complications could be found.

PMID- 11968577
TI  - [Pharmacotherapy of chronic obstructive pulmonary disease in patients with
      indications for long-term home oxygen therapy].
AB  - The authors submit a cross-sectional analysis of out-patient pharmacotherapy of
      chronic obstructive lung disease in 138 patients where long-term home oxygen
      therapy was indicated. To this group of patients no inhalatory bronchodilatating
      drugs were administered in 19.6% of the patients! The authors provide evidence of
      a non-significant better survival of patients who used inhalatory
      bronchodilatating drugs. From the mentioned group during the follow up period 41
      (29.7%) died with a mean survival of 16.5 +/- 11.9 (0-39) months. Based on the
      mentioned results the authors draw attention to the relatively late indication of
      long-term home oxygen therapy and also to the fact that pharmacotherapy of
      patients with chronic obstructive lung disease indicated for long-term home
      oxygen therapy is not fully exploited and its optimalization could lead to better
      patient survival.

PMID- 11968578
TI  - [Potential predictors of therapeutic response in patients with cryptogenic
      fibrosing alveolitis].
AB  - The authors present a clinical observation with the objective to test which
      objective indicators make it possible to predict the effect of treatment in
      patients with cryptogenic fibrotizing alveolitis. Retrospective analysis of the
      documentation of a longitudinal follow up of 34 patients with this diagnosis
      revealed that the presence of fibroproliferative changes on the high resolution
      CT image predicts significantly the absence of a therapeutic effect and
      conversely the absence of such changes predisposes for significant improvement of
      pulmonary functions during treatment. They found also a significant correlation
      between he ratio of lymphocytes in the bronchoalveolar lavage fluid and the
      dynamics of the development of pulmonary functions. The age of establishment of
      the diagnosis correlates also significantly with indicators of the therapeutic
      response. Based on these results the authors conclude that a favourable
      therapeutic effect can be expected in patients without fibroproliferative
      changes, with a significant lymphopcytosis in the bronchoalveolar lavage fluid
      and a younger age at the time of manifestation. On the other hand, in patients
      with a marked fibroproliferation and absence of alveolitis there is no point in
      attempting to influence the disease by pharmacological gents.

PMID- 11968579
TI  - [Hyperinsulinemia and disorders of the menstrual cycle].
AB  - Hyperinsulinaemia and insulin resistance are usually associated phenomena of
      obesity and the polycystic ovary syndrome (PCO syndrome). On the other hand the
      PCO syndrome and obesity are often associated with disorders of the menstrual
      cycle and/or sterility. The authors examined 35 women aged 21 to 38 years (x = 27
      +/- 4.4) with a history of anovulation cycles and/or sterility. 24 of them
      (68.6%) suffered from PCO syndrome. Their mean BMI was 28.95 kg/m2. 11 patients
      had a normal body weight, 6 were overweight and 18 were obese. The authors used
      the oral glucose tolerance test (oGTT) and during minute 0 and 120 blood samples
      were collected for assessment of the blood sugar and plasma insulin. Insulin
      levels in minute 0 (Io above 20 and in minute 120 (I120) above 65 uIU/ml were
      classified as hyperinsulinaemia. In the follicular stage of the anovulation cycle
      the authors assessed FSH, LH, testosterone, progesterone and prolactin.
      Hyperinsulinaemia ws recorded in 16 of 35 women. The mean insulin level at minute
      0 was 11.9 +/- 1.3 and during minute 120 54.2 +/- 8.1 uIU/ml. The authors found
      significant differences in levels of I0 (6.4 +/- 1.2 vs. 16.1 +/- 1.9 uIU/ml, p <
      0.01) and I120 (17.5 +/- 3 vs. 71.3 +/- 10.3 uIU/ml, p < 0.01) between obese and
      non-obese patients, Also in patients with the PCO there was a statistically
      significant difference in insulin levels of slim (BMI less than 25) as compared
      with obese women (BMI more than 30) (p < 0.01). A positive correlation was found
      between insulin levels and BMI (p < 0.01) and a liminal correlation between
      insulin and testosterone (p = 0.05). Patients with hyperinsulinaemia were treated
      with oral antidiabetics from the group of biguanides--metformin for a period of
      three months. During metformin treatment the insulin level declined and
      subsequently the menstrual cycle became normal in 11 of 16 patients with
      hyperinsulinaeia (68.7%), incl. two women who became pregnant. The results
      indicate a possible new indication of metformin in the treatment of ovarian
      hyperandrogenism in insulin resistant patients.

PMID- 11968581
TI  - [Determination of the end-point of the radiofrequency linear lesion in the
      subeustachian isthmus and its relation to treatment of atrial flutter and
      fibrillation. Acute and long-term results in 90 patients].
AB  - Complete subeustachian isthmus (isthmus) block created with radiofrequency (RF)
      linear lesion eliminates type I. atrial flutter (AFL). The end-point of the
      procedure is measurable. PATIENTS AND METHOD: Ninety patients (21 F) aged 57.6 +/
      12.5 years underwent RF catheter ablation for AFL. Twenty patients had
      significant structural heart disease (SHD). Atrial fibrillation (AF) was
      previously documented in 34 (37.8%) patients. Complete isthmus block served as
      the end-point of the procedure. RESULTS: Following the first ablation procedure
      complete isthmus block was achieved in 81 (90%) patients and incomplete isthmus
      block in 7 (7.8%) patients. First procedure failed in 2 (2.2%) patients. AFL
      recurred in 6 (6.8%) patients, in 4 (4.9%) out of 81 patients with complete
      isthmus block and in 2 (28.5%) out of 7 patients with incomplete isthmus block.
      After repeated successful ablation and creation of complete isthmus block in
      these 6 patients and in 1 patient with previous ablation failure, complete
      isthmus block was achieved in 84 (93.3%) patients, incomplete isthmus block in 5
      (5.6%) patients and ablation was unsuccessful in 1 patient. During 21 +/- 10.6 (6
      45) month follow-up since the last ablation AFL did not recur in any of 89
      (98.9%) patients with complete or advanced incomplete isthmus block. AF occurred
      in 39 (43.3%) patients. Incidence of AF was significantly higher in patients
      without SHD and with AF previously documented or induced (group 2) (25/43; 58.1%)
      compared to patients without SHD and no AF documented or induced (group 1) (6/27;
      22.2%) (p < 0.01). AF occurred in 40% patients with SHD (group 3), which did not
      significantly differ from any of the former two groups of patients. In this group
      AF occurred in 10 out of 12 (83.3%) patients with AF documented prior to
      ablation, which was significantly more compared to 1 (12.5%) patient out of 8
      without documented AF (p < 0.01). CONCLUSION: Complete conduction block over the
      subeustachian isthmus during catheter ablation has a clearly measurable end-point
      and represents effective method in permanent cure of AFL. Clinical benefit is
      reduced by AF, particularly in patients, in whom the arrhythmia was documented
      prior to ablation. In these patients catheter ablation of AFL can be considered a
      first step to combined treatment with previously ineffective antiarrhythmic drugs
      and with other ablation strategies.

PMID- 11968580
TI  - [Importance of determination of lymphocytes in intestinal mucosa biopsy specimens
      using flow cytometry in the evaluation of ulcerative colitis activity].
AB  - In this clinical study, we have examined 10 patients with ulcerative colitis. The
      study group included 5 men and 5 women. The control group consisted of 6 patients
      with negative colonoscopic finding performed for differential diagnosis of the
      dyspeptic syndrome. Patients with ulcerative colitis were divided into two groups
      according to the clinical pattern, macroscopic endoscopic finding, and
      histological examination of the bioptic specimens. The Ist group of patients with
      active stage of ulcerative colitis, the IInd group of patients in remission,
      without clinical and endoscopic signs of disease activity. We have found that
      from the followed markers the greatest importance lies in the determination of
      the standard immunologic profile of the mucosa, the determination of activating
      markers HLA-DR+, CD69, CD122 and CD71 on T-lymphocytes and CD69 and CD71 on B
      lymphocytes. The differences between the control group and the group of patients
      in active stage of the disease were statistically significant. Statistical
      significance was also found in some of the above-mentioned parameters when
      comparing the group of active disease and that one in remission (CD4/CD8 ratio,
      HLA-DR+, CD122 on T-lymphocytes). Our results imply that the changes in the
      target tissue contribute to more precise assessment and follow-up of therapeutic
      effect in non-specific inflammatory bowel disease.

PMID- 11968582
TI  - [Sonographic study of the diameter of the inferior vena cava for optimal
      ultrafiltration in hemodialysis].
AB  - The objective of the work was to evaluate the results of sonographic examination
      of the diameter of the vena cava inferior (VCI) as a parameter of hydratation of
      haemodialyzed patients. In a group of 84 haemodialyzed patients, mean age 66.32
      years, the collapsibility index of the IVC was measure. The collapsibility index
      (CI) was calculated according to the formula: [formula: see text] where IVCexp =
      the maximum diameter of the IVC in maximum inspiration. Values of the index
      within the range from 40-75% corresponded to normal hydratation. The results were
      compared with ultrafiltration (total and expressed as % of body weight after
      haemodialyzation), "dry" body weight and with changes of BP during haemodialysis.
      The mean value of CI was 63.24 +/- 18.54. In 54 instances it was within the
      normal range (62.26 +/- 11.4), in 10 it was lower (27.7 +/- 6.02; possible sign
      of inadequate ultrafiltration during dialysis) and in 20 instances it was higher
      (84.9 +/- 7.53; risk of excessive ultrafiltration). Clinically assessed "dry"
      weight was adequate in 64% cases. In 24% UF was excessive. With this corresponded
      also the incidence of hypotension (40%) and in these patients the "dry" weight
      was subsequently elevated. The predictive importance of low values of CI for
      inadequate UF is however not unequivocal. Some of these patients were hypotensive
      even in case of low UF and did not tolerate its increase.

PMID- 11968584
TI  - [New views on the treatment of chronic myelocytic leukemia. Literature review].
AB  - The expansion of knowledge of molecular biology and pathophysiology of chronic
      myeloid leukaemia (CML) indicate a new therapeutic approaches of the disease.
      Besides less toxic nonmyeloablative regimes of allogenEic transplantation and the
      introduction of modified interpherone regimes attracts our interest therapy more
      specific, aimed to a primary reason of a disease, BCR/ABL gene, and its products,
      that are responsible for leukaemic transformation. The paper is a summary of
      experimental, as well as first clinical experiences with application of
      thyrosinkinase-inhibitors, farnesyl-transferase-inhibitors and vaccination
      therapy of CML. Even thought is allogeneic transplantation the only curative
      therapy of CML, first clinical experiences with thyrosinkinase inhibitors show,
      that these are the medicaments that can become in a near future its important
      alternative.

PMID- 11968583
TI  - [Quality of life and tolerance of maintenance therapy in patients with multiple
      myeloma].
AB  - Questionnaires on the quality of life and tolerance of different parts of
      maintenance treatment were sent to a total of 83 patients with multiple myeloma.
      All patients were for more than one year on maintenance treatment which involved
      either interferon alpha monotherapy (I), 3 million u. three times per week till
      signs of relapse developed or sequence administration of interferon alpha and
      dexamethazone 40 mg on day 1 to 4, 10 to 13 and 20 to 23 and then after a four
      week interval again interferon alpha, again till progression of the disease
      occurred. The patients evaluated the presence or absence of different undesirable
      effects of treatment during the first two weeks of treatment and throughout the
      year and listed their intensity into four categories defined in the
      questionnaire. The quality of life was evaluated by means of a basic module of
      the questionnaire of the European Organization for Research and Treatment of
      Cancer Core Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30). The
      results of the questionnaire are to a certain extent surprising as from the
      patients' answers ensues that this maintenance treatment is associated with more
      numerous undesirable effects than the physicians realized when in contact with
      the patient. In this summary we can list only the most frequent effects
      (deterioration of eyesight, impaired sleep, depressions, irritability and unrest,
      chill, pain in muscles and joints, general weakness and dyspnoea). From the
      questionnaires on the quality of life ensues a markedly poorer quality of life of
      these patients as compared with the healthy population. There are however no
      basic differences between individual groups. The questionnaires were handed only
      to patients who had maintenance treatment for more than one year and thus
      patients were eliminated where maintenance treatment was discontinued because of
      undesirable effects. To give a general idea of the tolerance of the above
      maintenance treatment the authors mention that to the date of Aug. 31, 2001 113
      patients were randomized into one of the branches of maintenance treatment.
      Maintenance treatment had to be discontinued in 6% patients (in two instances on
      account of severe hypothyroidism, in one case on account of hallucinations, in
      three instances on account of severe mental depression caused by this treatment).
      Reduction of interferon doses in 20% patients usually because of cytopenia but
      also on account of psychic problem. To the question what length of prolongation
      of life compensates the undesirable effects of maintenance treatment the
      following replies were obtained from patients receiving ID, possibly I: 3 months-
      47.6 and 38.3%, 6 months--4.3 and 10.6%, 9 months--0 and 4.3%, 12 months--47.6
      and 46.8% of the addressed patients. In reply to the question whether the
      patients would prefer, assuming equal effectiveness, a maintenance monotherapy
      with interferon alpha or dexamethazone more patients preferred interferon to
      dexamethasone. For practice ensues from this article informing on undesirable
      effects of maintenance treatment and the effect of maintenance treatment on the
      quality of life: 1. the necessity of thorough knowledge of physicians of all
      possible undesirable effects as only a doctor knowing possible undesirable
      effects of treatment can recognize them, 2. regular monitoring not only of the
      activity of the basic disease, but also undesirable effects of maintenance
      treatment and the influence of treatment on the patients' quality of life, 3. the
      necessity to assess the quality of life in clinical trials as an important
      parameter for deciding on the way of treatment.

PMID- 11968585
TI  - [Sudden cardiac death (part 2)].
AB  - In addition to acute treatment of sudden cardiac death the authors focus
      attention in particular on an analysis of long-term diagnostic and therapeutic
      provisions to cope with this serious clinical condition. The basic therapeutic
      procedures include influencing of the arrythmogenic substrate and modulating
      factors associated with the development of tachyarrhythmias by revascularization
      of the myocardium and radiofrequency ablation; as to drugs in particular by
      administration of angiotensin converting enzyme inhibitors and in rare instances
      by the application of other surgical methods. Haemodynamically important
      ventricular arrhythmias are treated by antiarrhythmics (beta-blockers,
      amiodarone, sotalol) and an implantable cardioverter-defibrillator. In the
      conclusion the authors propose a diagnostic therapeutic algorithm after
      circulatory arrest with successful cardiopulmonary resuscitation.

PMID- 11968586
TI  - [Determination of blood pressure sensitivity to salt].
AB  - Considerable evidence has accumulated indicating that sodium sensitivity of blood
      pressure is an important prognostic factor in hypertension. This review article
      focuses on methods used to define salt sensitivity in man. The linear
      approximation of pressure-natriuresis curve has made it possible to elaborate
      reliable non-invasive approaches for distinguishing salt-sensitive from salt
      resistant forms of human hypertension. The sodium sensitivity index, calculated
      as the ratio of the change in mean arterial pressure over the change in
      natriuresis, can be calculated to characterize hypertension. Literary data show
      that salt sensitivity increases with age and that more salt-sensitive persons
      exist among hypertensive than among normotensive individuals (about 40-50% vs. 25
      40%, respectively, provided the daily salt does not exceed 25 g).

PMID- 11968587
TI  - [Prevention of mycotic infections in oncology patients with regard to the
      toxicity of antimycotic agents].
AB  - Profound and prolonged neutropenia following chemotherapy is a major risk factor
      for systemic fungal infections. It is still unclear how effective the various
      measures that are currently being used are in preventing serious fungal
      infection. Although a number of studies have been published on antifungal
      prophylaxis in neutropenic patients, there are a lot of conflicting data. At the
      present time, it seems that antifungal prophylaxis is more a matter of faith
      rather than science. The prophylactic use of fluconazole or itraconazole may
      reduce the incidence of systemic fungal infections in high-risk patient groups,
      mainly in patients with haematological malignancies. The antifungals currently
      used for prophylaxis in immunocompromised patients, and the toxicity of the
      antifungals are reviewed.

PMID- 11968588
TI  - [The Brugada syndrome].
AB  - On the case of a patient who had medical care on account of a febrile disease
      diagnosed as pleuritis the authors draw attention to a relatively new
      pathological unit described as the "Brugada syndrome". It is a genetically
      conditioned anomaly of sodium channels, which, when fully expressed, is
      manifested by a picture resembling right bundle branch block, elevation of ST
      segment in leads V1-V3 and the occurrence of malignant ventricular arrhythmias or
      sudden death without structural heart disease. Neither the reported patient nor
      his family suffered from arrhythmias. The authors present however a typical
      electrocardiographic picture ad positive test with ajmaline, a substance which by
      blocking sodium channels can frequently induce latent and variable changes.

PMID- 11968590
TI  - Trustee workbook 2. Diagnosing the health of your organization: early warning
      signs.

PMID- 11968589
TI  - [Richter's syndrome (bimorphologic malignant lymphoma)].
AB  - Two distinct morphological types of malignant lymphoma in the same patient occur
      mostly due to transformation of a low grade lymphoma (CLL) into a large--cell non
      Hodgkin lymphoma (high-grade lymphoma). Later reports have brough evidence of a
      clonal relationship between CLL and supervening NHL. The Richter's syndrome was
      found to be more frequent in patients with CLL displaying either multiple
      chromosomal aberrations or monoclonal gammapaties. In the last two decades
      reports have evidenced the existence of two types of the Richter's syndrome: one,
      the "classical" as a terminal event in a long evolving CLL, the other "variant"
      as the first clinical manifestation of a previously unrecognized subclinical CLL.
      Aggressive chemotherapy of CLL play a role in transformation of CLL to Richter's
      syndrome.

PMID- 11968591
TI  - An investment in community. Foster McGaw Prize winner has the ten percent
      solution.

PMID- 11968592
TI  - Hospital closure: making the best of a difficult decision.

PMID- 11968593
TI  - In the defense of hospitals: taking the high road.

PMID- 11968594
TI  - Technology. Improving your return on IT.

PMID- 11968595
TI  - A new attitude: changing organizational culture.
AB  - When everyone in your organization--starting with the board--all share the same
      values and demonstrate them through their behavior, the organization is on the
      road to success. Three case studies illustrate how to change or strengthen your
      culture.

PMID- 11968596
TI  - Nil by mouth.

PMID- 11968597
TI  - Nutritional assessment and screening in children.

PMID- 11968598
TI  - A multidisciplinary PEG service and the nurse specialist.

PMID- 11968600
TI  - When and how to use iodine dressings.

PMID- 11968601
TI  - Managing risk in tissue viability. Part 2.

PMID- 11968602
TI  - Photography in wound care.

PMID- 11968603
TI  - Cut the risk with quality care.

PMID- 11968604
TI  - A pressure damage prevention strategy.

PMID- 11968605
TI  - Using sugar paste to heal postoperative wounds.

PMID- 11968606
TI  - Prescribing: the role of the tissue viability nurse.

PMID- 11968607
TI  - When and how to use foam dressings.

PMID- 11968608
TI  - Managing risk in tissue viability.

PMID- 11968609
TI  - Mattresses and beds: reducing and relieving pressure.

PMID- 11968610
TI  - London trust in a royal mess.

PMID- 11968611
TI  - Tsar slams prostate screening.

PMID- 11968612
TI  - Hotline to beat winter blues.

PMID- 11968613
TI  - Motherhood and methadone.

PMID- 11968614
TI  - Should fertility treatment be used for the benefit of siblings?

PMID- 11968615
TI  - People in glass houses.

PMID- 11968618
TI  - Contemporary nursing's missing link.

PMID- 11968620
TI  - We're all to blame.

PMID- 11968621
TI  - One weigh or another.

PMID- 11968622
TI  - Reality bites.

PMID- 11968624
TI  - Altered estates: the regeneration game.

PMID- 11968623
TI  - Keep children safe.

PMID- 11968625
TI  - Risk assessment matrix for MRSA.

PMID- 11968626
TI  - Nut allergy and acute anaphylaxis management.

PMID- 11968627
TI  - Audit of nursing handover.

PMID- 11968628
TI  - Management of leg ulcers--1.

PMID- 11968629
TI  - Days of helping.

PMID- 11968631
TI  - In the pink. Breast cancer is down, but not out.

PMID- 11968632
TI  - Can the rest follow this strong lead?

PMID- 11968633
TI  - Has this Labour government been good for the NHS?

PMID- 11968634
TI  - We must curb antibiotic resistance.

PMID- 11968637
TI  - We just can't go on like this.

PMID- 11968636
TI  - Keep the accountants out of nursing.

PMID- 11968638
TI  - Practice makes perfect.

PMID- 11968639
TI  - Taking a lead in running local health services.

PMID- 11968640
TI  - Uneasy choices.

PMID- 11968641
TI  - Breast care--an overview.

PMID- 11968642
TI  - Nursing practice in gestational trophoblastic disease.

PMID- 11968643
TI  - Suicide in the ward setting.

PMID- 11968644
TI  - How to set up a stroke register.

PMID- 11968645
TI  - Systems and diseases. Exploring normal anatomy and physiology. Nervous System. 2.

PMID- 11968646
TI  - The magic of theatre.

PMID- 11968650
TI  - Dishing the dirt on smelly hospital wards.

PMID- 11968651
TI  - In? Out? This result will shake the RCN all about.

PMID- 11968652
TI  - Medical errors. The usual mistakes.

PMID- 11968653
TI  - Alcohol survey. We're going down the pub.

PMID- 11968654
TI  - Should the RCN admit health care assistants?

PMID- 11968655
TI  - If they can put a man on the moon....

PMID- 11968659
TI  - Public health. Airtime.

PMID- 11968660
TI  - Confidence tricks.

PMID- 11968661
TI  - Ordering diagnostic investigations.

PMID- 11968662
TI  - Skin assessment in children: a methodical approach.

PMID- 11968664
TI  - Development of discharge skills: a project report.

PMID- 11968663
TI  - Meeting patients' post-discharge needs after lung cancer surgery.

PMID- 11968665
TI  - Silent night?

PMID- 11968667
TI  - Nurse networks in learning disability.

PMID- 11968668
TI  - Catheterisation using lignocaine gel.

PMID- 11968670
TI  - Six weeks in Tibet.

PMID- 11968674
TI  - Genetics. 'We made the perfect decision'. Interview by Caroline Ryan.

PMID- 11968675
TI  - What is Ebola?

PMID- 11968676
TI  - 'I'm transparent and open'. Interview by Carolyn Ryan.

PMID- 11968677
TI  - Girl interrupted.

PMID- 11968678
TI  - Should nurses take part in demonstrations?

PMID- 11968679
TI  - Beyond belief.

PMID- 11968683
TI  - Now wash your hands.

PMID- 11968684
TI  - Which party has the X factor?

PMID- 11968685
TI  - Retire & return.

PMID- 11968686
TI  - If you go down to A&E today.

PMID- 11968687
TI  - Ear-syringing and aural care.

PMID- 11968688
TI  - Leadership skills for ward sisters and charge nurses.

PMID- 11968690
TI  - Nurse prescribing in the field of community mental health nursing.

PMID- 11968689
TI  - Day-case surgery and family response.

PMID- 11968691
TI  - Group work for older people with mental health problems.

PMID- 11968692
TI  - Management of leg ulcers--2.

PMID- 11968694
TI  - Not all plain sailing.

PMID- 11968703
TI  - [Long-term results of aortic arch replacement using combination of deep
      hypothermic circulatory arrest and retrograde cerebral perfusion; comparison of
      result for atherosclerotic aneurysm and aortic dissection].
AB  - Between 1992 and 2001, 73 patients with aortic arch lesion underwent surgical
      treatment. The aneurysm was characterized by atherosclerosis in 54 patients (TAA)
      and by aortic dissection in 19 patients (DAA). All patients received graft
      replacement under combination of deep hypothermic circulatory arrest and
      retrograde cerebral perfusion. The hospital mortality rate for all patients was
      15.6%. The follow-up period of 61 survival patients ranged from 2 to 90 months
      (mean 33.2 months). The actuarial survival rate was 93.2%, 83.5%, and 79.7% at 1,
      3, and 5 years, respectively. No significant difference was noted between TAA and
      DAA in the actuarial survival rate. The freedom from vascular complication was
      97.9%, 95.8%, and 95.8% at 1, 3, and 5 years, respectively. The rate was
      significant higher in the patients of DAA than in those of TAA (TAA: 100%, 100%,
      and 100%, DAA: 90.9%, 81.8%, and 81.8%). The freedom from cardiac complication
      was 96.4%, 89.7%, and 84.1% at 1, 3, and 5 years, respectively. There was no
      significant difference between TAA and DAA. The freedom from cerebrovascular
      complication was 100%, 97.6%, and 83.4% at 1, 3, and 5 years, respectively. No
      significant difference was noted between TAA and DAA. The late result of surgical
      treatment for the aortic arch using combination of deep hypothermic circulatory
      arrest and retrograde cerebral perfusion was satisfied. The long-term survival
      rate was higher in TAA patient than in DAA one. The possibility remained that
      fatal vascular complication affected the long-term survival rate.

PMID- 11968704
TI  - [Long-term results after surgery for aortic arch nondissection aneurysm].
AB  - Between 1990 and August 2001, 109 patients were treated surgically for
      nondissection fusiform or saccular aortic arch aneurysm. Fifteen patients were
      emergent. There were 89 male and 20 female patients (mean 71.7 +/- 6, range 49 to
      84). Eight patients underwent hemiarch replacement, 57 total arch replacement, 44
      distal arch replacement, which were performed with the aid of hypothermic
      extracorporeal circulation with antegrade selective cerebral perfusion or
      retrograde cerebral perfusion. The early mortality was 8.5% with elective
      operations and 53.3% with emergent operations. The incidence of post operative
      permanent neurological dysfunction was 12.8% with elective operations and 46.7%
      with emergent operations. The 5-year and 10-year survival rate including in
      hospital deaths was 52 +/- 6% and 29 +/- 9%. The 5-year event free rate was 89 +/
      5%.

PMID- 11968705
TI  - [Early and late survival of total aortic arch replacement in patients with
      dissecting or atherosclerotic aneurysm].
AB  - Forty-seven patients (pts) were underwent total aortic arch replacement (TAAR)
      were studied to compare the early and late results between atherosclerotic (AA)
      and dissecting aneurysm (DA). There were 23 pts with AA and 24 pts with 24 pts.
      Preoperative risk were observed with shock in 12 pts (26%), major organ ischemia
      in 2 pts (4%), rupture in 8 pts (17%), stroke in 8 pts (17%) and coronary artery
      disease in 4 pts (9%). Operative procedure was TAAR in 22 pts, TAAR with
      ascending aorta replacement in 14 pts, and TAA with descending aorta replacement
      in 11 pts. Hospital mortality was 21 pts (45%) and late mortality was a surgical
      death after thoracoabdominal aneurysm in 1 pts. There was no difference in early
      and late survival rate, however early mortality was higher in pts with ruptured
      AA and with DA suffered from preoperative shock. There were 19 of early death in
      recent pts without rupture in AA and preoperative shock in DA.

PMID- 11968706
TI  - [Early and long-term outcome for surgical treatment of aortic arch aneurysm].
AB  - This study was undertaken to determine the factors that influence the final
      outcome after the operation of aortic arch aneurysm. Sixty-six patients, the
      median age was 72 years (range 44 to 90), were operated at our hospital during
      the 16-year period between 1985 and 2001. Preoperative complications included
      cardiac in 6 and vascular in 21, ruptured in 13, myocardial ischemia in 21 and
      stroke in 14. The distal hemiarch (11) and total arch replacement with or without
      ascending aorta and descending aorta (46) and proximal hemiarch with or without
      valve operations (7) and other procedures were performed mainly using cardio
      pulmonary bypass with moderate deep hypothermia and selective cerebral perfusion.
      The in-hospital mortality were 6 (9%) and 14 (23%) late deaths occurred. One out
      of 14 was aneurysm related death. The survival rates were 81% at 1 year and 59%
      at 5 years. The multivariably determined risk factors for early death and
      postoperative neurological dysfunction were as follows (p < 0.05) cardiac anoxic
      arrest time, intubation time and gender.

PMID- 11968707
TI  - [True aneurysm of the ascending aorta and/or aortic arch; determinants of late
      surgical outcome].
AB  - To identify significant predictors of late mortality, multivariate analysis were
      applied to the clinical outcome of 150 consecutive patients with true aneurysm of
      the ascending aorta and/or aortic arch operated between January, 1987 and
      December, 2000. Mean follow-up was 53.0 months with a total of 6,682 patient
      months of follow-up. Multivariate analysis revealed that operation date (before
      December, 1996), presence of preoperative cerebrovascular disease, rupture and
      postoperative phrenic nerve palsy were independent determinants of late
      mortality. The overall 5-year and 10-year actuarial survival rates were 66.0% and
      48.2%. The 5-year and 10-year event free rate of cardiovascular and/or
      cerebrovascular death were 88.9% and 71.7%. Preoperative evaluation of the brain,
      operation prior to aneurysm rupture and phrenic nerve protection during operation
      is necessary to improve long-term survival rate.

PMID- 11968708
TI  - [Long-term surgical outcomes of aortic arch aneurysm].
AB  - Between January 1990 and October 2001, arch replacement was performed in 99
      patients with aortic arch aneurysm at Omiya Medical Center. For brain protection
      during surgery, antegrade selective cerebral perfusion was performed. There were
      11 (11.1%) hospital death, and causes were heart failure (3), pneumonia (2),
      respiratory failure (1), mediastinitis (1), cerebral infarction (1), sepsis (1),
      myocardial infarction (1), and bleeding (1). During follow-up, 24 patients died,
      and causes were pneumonia (4), malignancy (3), heart failure (2), cerebral
      infarction (2), rupture of residual aneurysm (2), asthma (1), myocardial
      infarction (1), sepsis (1), multiple organ failure (1), traffic accident (1), and
      unknown (6). Postoperative survival was 75.2% at 3 years, 61.5% at 5 years, and
      35.3% at 8 years. Event free ratio was 71.8% at 3 years, 58.6% at 5 years, and
      30.8% at 8 years. Surgery of the aortic arch using selective cerebral perfusion
      is a safe and demonstrated acceptable short- and long-term outcomes.

PMID- 11968709
TI  - [Long-term results of the operation for the aortic arch aneurysm].
AB  - Between October, 1991, and October, 2001, 60 patients underwent aortic arch
      replacement with or without an aortic arch branched graft for atherosclerotic
      arch aneurysms. Their mean age was 70.1 +/- 8.6 years. Eight (13.3%) patients
      were operated on an emergency basis because of rupture or impending rupture of
      aneurysms. All operations were performed with hypothermic extracorporeal
      circulation. Selective cerebral perfusion for cerebral protection during aortic
      arch repair and systemic circulatory arrest during distal graft anastomosis was
      used in 56 patients. Mean selective cerebral perfusion time was 86.1 +/- 12.1
      minutes. A total of 14 concomitant procedures were done. Overall in-hospital
      mortality was 3.3%. Postoperative temporary and permanent neurologic dysfunction
      were 1.6% and 1.6%. Long-term follow-up was 100% complete. There were 6 late
      deaths with the cumulative survival rate was 74.6 +/- 8.8%. A subsequent aortic
      operation was necessary for the treatment of an aortic abnormality distal to the
      arch in 6 patients. Reoperation free rate was 85.2 +/- 5.8%. In conclusion,
      cerebral protective effect of antegrade selective cerebral perfusion and total
      arch replacement with an aortic arch branched graft could substantially reduce in
      hospital mortality and postoperative neurologic dysfunction and a satisfactory
      long-term results could be obtain in patients with atherosclerotic arch
      aneurysms.

PMID- 11968710
TI  - [Early and long-term results of surgery for aortic arch aneurysms using selective
      cerebral perfusion].
AB  - OBJECTIVE: We report our operative technique for atherosclerotic arch aneurysms
      and early and long term results of the surgery. METHODS: Between April 1992 and
      December 2001, 80 consecutive patients underwent operation for atherosclerotic
      arch aneurysms. Their mean age was 70 +/- 7 years. Sixty-six (82.5%) patients
      were operated on electively. All operations were performed under median
      sternotomy using hypothermic circulatory arrest and selective antegrade cerebral
      perfusion. Total arch replacement was performed in 66 cases, proximal hemiarch
      replacement in 4 cases, distal arch replacement using stent graft implantation
      via aortic arch incision in 8 cases, and patch angioplasty in 2 cases. In 9 of
      these patients in whom mobile arch atheroma was revealed by intraoperative
      epiaortic ultrasonography, isolation technique was employed to avoid embolic
      stroke. RESULTS: Overall in-hospital mortality was 10.0% (8 of 80 patients).
      Postoperative temporary neurologic dysfunction was 7.5%, and stroke rate was
      5.0%. The 3-year, and 5-year actuarial survival rate including hospital death was
      79.3% and 75.3% respectively. The 3-year, and 5-year cardiovascular event free
      survival rate was 68.3% and 60.0% respectively. CONCLUSION: The early and long
      term results of surgery for atherosclerotic arch aneurysms were acceptable.
      Selective cerebral perfusion is an effective brain protective adjunct.

PMID- 11968711
TI  - [Total arch replacement using prior selective cerebral perfusion].
AB  - Prior selective cerebral perfusion is the method whereby selective cerebral
      perfusion and systemic perfusion start almost simultaneously, and the arch
      vessels are clamped. Cerebral circulation is isolated from systemic circulation
      to avoid cerebral embolization owing to detachment of atherosclerotic material
      from the aorta, caused by the "sandblasting" effect of high-velocity jets of
      blood exiting the aortic canula. Twenty-seven consecutive patients underwent
      total arch replacement for degenerative aortic arch aneurysm using prior
      selective cerebral perfusion from 1992 to 2001. Surgical death (within 1 month
      after operation) was 2 cases (7.4%), in-hospital death was 5 cases (18.5%).
      Systemic circulatory arrest time is almost equal to the time which distal
      anastomosis takes. The time was 81.4 +/- 24.3 minutes. Selective cerebral
      perfusion time was 194.9 +/- 30.9 minutes. Extracorporeal circulation time was
      280.6 +/- 55.3 minutes. The time for emergence from anesthesia was 6.0 +/- 2.7
      hours. Permanent neurologic dysfunction which was thought to occurred within 48
      hours after surgery was noted in 1 case (3.7%). Postoperative survival at 8 years
      was 73.3%. There was 1 arch aneurismal related accident. Prior selective cerebral
      perfusion may be useful for avoiding cerebral embolization.

PMID- 11968712
TI  - [Long-term results of total aortic arch replacement using selective cerebral
      perfusion].
AB  - From June 1994 to July 2001, 92 consecutive patients underwent total aortic arch
      replacement using hypothermic selective cerebral perfusion. Forty-four patients
      had nondissecting fusiform or saccular aneurysms (non-ruptured 34, ruptured 10),
      and 48 patients had dissection (acute 37, chronic 11). Hospital mortality rate
      was 6.8% in the nondissecting group and 6.3% in the dissecting group. No major
      operative cerebral complications were observed. There were 9 late deaths in the
      nondissecting group and 5 late deaths in the dissecting group. The actuarial
      survival rate was 61.6% after 100 months in the nondissecting group and 82.5%
      after 86 months in the dissecting group (p = 0.5128). In the postoperative aortic
      accidents, there were 2 cases of the descending aortic rupture and 2 cases of
      cholesterol crystal embolization in the nondissecting group and 3 cases of
      thoracoabdominal grafting, 2 cases of re-operation in the ascending aorta and 1
      case of descending aortic rupture in the dissection group. The actuarial freedom
      from aortic accidents was 88% after 100 months in the nondissecting group and 80%
      after 86 months in the dissecting group (p = 0.6908). Our surgical outcome of
      total aortic arch replacement using hypothermic selective cerebral perfusion are
      satisfactory.

PMID- 11968713
TI  - [Selections of aortic reconstruction procedures and brain protection methods
      during aortic arch repairs; including mid-term survival and freedom from cerebral
      infarction].
AB  - Aortic reconstruction procedures and brain protection methods are very important
      among operative factors that have direct influence on surgical results. We
      nowadays use hypothermic circulatory arrest (HCA) with or without retrograde
      cerebral perfusion (RCP) as brain protection methods during hemiarch replacement
      (HAR) and selective cerebral perfusion (SCP) during total arch replacement (TAR)
      using 4-branched arch graft. The purpose of this study was to verify the
      appropriateness of this strategy. From April 1997 to August 2001, we performed
      120 TAR assisted by SCP and 30 HAR assisted by HCA with or without RCP.
      Incidences of in-hospital death and postoperative neurological dysfunction were
      compared between the 2 groups. In-hospital deaths were 4 (3.3%) and 1 (3.3%),
      permanent neurological dysfunction were 3 (2.5%) and 1 (3.3%), temporary
      neurological dysfunction were 4 (3.3%) and 1 (3.3%), 3-year survival were 92 +/-
      3% and 97 +/- 3% and cerebral infarctions after discharge were 2 and 0 in TAR and
      HAR, respectively. Appropriate selections of aortic reconstruction procedures and
      brain protection methods lead to good operative results in aortic arch repairs.

PMID- 11968714
TI  - [Mid-term outcome of aortic arch operation for true aneurysms; using an axillary
      artery perfusion].
AB  - To prevent cerebral infarction during perioperative period, we have used an
      axillary artery for systemic perfusion and selective cerebral perfusion for
      aortic arch operation. Since 1996, 34 aortic arch operations were performed in
      our institution. Simultaneous 5 CABGs, 4 AVRs, 2 aortic root replacements and 1
      MVR were performed. There were 2 hospital deaths (5.9%, sepsis and acute heart
      failure) and only 1 (2.9%) cerebral infarction. There were no deaths in patients
      over 75 years of age and in patients with extensive aneurysm which were replaced
      by 2-staged operation. Overall 3 years survival was 94.1% with no further death.
      We conclude that aortic arch operation through an axillary artery perfusion and
      with hypothermic selective cerebral perfusion can be performed with very low
      mortality and morbidity.

PMID- 11968716
TI  - Girdling effect of adynamic cardiomyoplasty in a model of dilated cardiomyopathy.
AB  - OBJECTIVE: The potential benefits of adynamic cardiomyoplasty remain unclear. We
      determined whether unstimulated skeletal muscle wrap alone prevents or attenuates
      progressive left ventricular dilation in a canine model of congestive heart
      failure produced by repeated intracoronary infusions of doxorubicin. SUBJECTS AND
      METHODS: 14 dogs were randomized in to 2 groups, 1 undergoing cardiomyoplasty
      (CMP group) and 1 that did not (CONT group). Intracoronary doxorubicin was
      administered weekly for 5 weeks to induce heart failure. Hemodynamic data was
      obtained before infusion and 5 weeks afterward. Echocardiography was done weekly.
      RESULTS: Significant left ventricular dilation was observed in the CONT group-
      left ventricular end-diastolic diameter increased from 28.9 +/- 2.7 to 38.5 +/-
      3.3 mm (p < 0.05). Significant left ventricular dilation was also observed in the
      CMP group--left ventricular end-diastolic diameter increased from 28.9 +/- 3.3 to
      38.0 +/- 4.2 mm (p < 0.05). Dilation was slower in the CMP group than in the CONT
      group, however. Ejection fraction decreased from 58.0 +/- 13.8 to 29.9 +/- 13.7%
      in the CONT group, but was preserved from 56.0 +/- 8.8 to 51.9 +/- 10.3% in the
      CMP group. CONCLUSIONS: Adynamic cardiomyoplasty reduces ventricular dilation
      associated with heart failure without exacerbating left ventricular dysfunction.

PMID- 11968715
TI  - [Mid-term results of the surgery for aortic arch aneurysm].
AB  - One-hundred-one surgeries for aortic arch aneurysm were divided into 2 groups: 52
      aortic dissection cases (AD) and 49 non-dissecting aneurysm (TA). In group AD, 30
      cases were operated in acute phase (acute AD) and 22 were in chronic phase
      (chronic AD). Preoperative shock were observed in 21 cases (15 in acute AD mostly
      due to cardiac tamponade, 1 in chronic AD and 5 in TA due to rupture). Through
      median sternotomy, 59 total arch replacement and 25 hemi-arch replacement were
      carried out under deep hypothermia (16 degrees C:DH) and retrograde (RCP) or
      selective (SCP) cerebral perfusion or arch-first technique. Through thoracotomy,
      distal arch replacement were carried out with DH + RCP in 8 cases and with
      partial bypass in 9. Early mortality were observed in 7 patients (6.9%) and 24
      months survival rates (Kaplan-Meier) were 86.1% overall, 76.1% in acute AD, 95.5%
      in chronic AD, 87.8% in TA. The survival rates in patients with preoperative
      shock was 61.2%, however, without shock, 92.9% in acute AD, 95.2% in chronic AD,
      and 91.4% in TA. Other than mortality, 4 re-operations for aortic arch, 4
      operations for descending to abdominal aorta and 1 late hemiplegia were observed.
      Aortic event free ratio at 24 months was 55.4% in acute AD, 94.4% in chronic AD,
      and 75.7% in TA. For the further improvement of aortic arch surgery, early
      mortality and residual false lumen in acute aortic dissection and atherosclerotic
      aneurysm in descending to abdominal aorta are focused.

PMID- 11968717
TI  - Effect of deep hypothermia on cerebral hemodynamics during selective cerebral
      perfusion with systemic circulatory arrest.
AB  - OBJECTIVE: We studied the effect of deep hypothermia on cerebral hemodynamics
      during selective cerebral perfusion with systemic circulatory arrest. METHODS:
      Ten anesthesized pigs were placed on cardiopulmonary bypass and cooled to a
      rectal temperature of 22 degrees C (n = 5) or 15 degrees C (n = 5). During
      selective cerebral perfusion, the descending aorta was clamped and perfusion of
      the lower body was discontinued. As the pump flow was changed, we monitored the
      perfusion pressure, local cerebral blood flow, and local cerebral oxygenation
      using laser Doppler flowmetry and near-infrared spectroscopy. We also measured
      the free flow of the left internal thoracic artery during selective cerebral
      perfusion. RESULTS: Perfusion pressure and local cerebral blood flow decreased as
      the pump flow decreased. Oxygenated and deoxygenated hemoglobin in cerebral
      tissue remained unchanged at a perfusion flow of 10 ml/kg/min, whereas oxygenated
      hemoglobin decreased and deoxygenated hemoglobin increased progressively and
      reciprocally as the pump flow decreased. The pump flow for maintaining perfusion
      pressure above 35 mmHg with stabilized local cerebral oxygenation was
      significantly higher at 15 degrees C than at 22 degrees C. The internal thoracic
      artery free flow was higher at 15 degrees C than at 22 degrees C. CONCLUSIONS:
      Selective hypothermic cerebral perfusion with systemic circulatory arrest
      produces an extracranial shunt through the internal thoracic artery, especially
      under deep hypothermia. Our data suggests that selective cerebral perfusion
      during deep hypothermia is best managed by perfusion pressure control rather than
      by flow control.

PMID- 11968718
TI  - Right-side congenital pericardial defect associated with ischemic heart disease.
AB  - We report an unusual right-side congenital pericardial defect with herniation of
      the right atrium to the right thoracic cavity found intraoperatively in a 73-
      year-old man undergoing coronary artery bypass grafting for triple-vessel
      coronary artery disease. The right atrial wall showed fibrous changes due to
      contact with the defect edge. We suspected that the right coronary artery was
      obstructed by chronic strangulation of the right atrium. We repaired the defect
      with a polytetrafluoroethylene patch to prevent it from compressing the bypass
      graft and coronary arteries.

PMID- 11968719
TI  - Acute aortic dissection involving an aberrant right subclavian artery.
AB  - Although the aberrant right subclavian artery is the most common abnormality in
      aortic arch development, it is unusual to encounter this abnormality when
      repairing acute aortic dissection. We report a case of Stanford type A acute
      aortic dissection involving an aberrant right subclavian artery in a 45-year-old
      man. We used the elephant trunk procedure to surgically manage the intimal tear
      and aberrant right subclavian artery. This is, to our knowledge, the first report
      in Japan of surgical reconstruction of an aberrant right subclavian artery in
      conjunction with acute aortic dissection.

PMID- 11968720
TI  - Carcinoma positive for Epstein-Barr virus staining. Mediastinal lymph node
      origination?
AB  - A 44-year-old man undergoing radical excision of metastatic carcinoma of the
      mediastinal lymph node with unknown primary sites remains alive and disease-free
      14 years after surgery. His cancer cells were positive for the Epstein-Barr
      virus, which may have been related to the oncogenesis of this tumor. This case is
      unique in the patient's long, disease-free survival and its positive presence of
      the Epstein-Barr virus.

PMID- 11968721
TI  - Arterial embolization to preoperatively manage pulmonary disease associated with
      inflammation.
AB  - Preoperative arterial embolization is used in pulmonary disease to reduce
      intraoperative blood loss resulting from exposure of extensive adherent pleura
      due to repeated inflammation. Between January 1996 and February 2001, 5 patients
      underwent surgery with this procedure. Underlying diseases were 3 cases of
      aspergilloma and 1 each of chronic expanding hematoma and lung cancer. All
      embolization was permanent, involving coil insertion. Surgical treatment was
      successful in all 5 patients without mortality. Such preoperative management
      proved useful in reducing intraoperative blood loss in hypervascular collateral
      feeding vessels in the area of resection or decortication.

PMID- 11968722
TI  - Surgical repair of a pseudoaneurysm derived from a nine-year-old saphenous vein
      graft after coronary artery bypass.
AB  - A 57-year-old male presented intermittent pain between the left shoulder and
      neck. He had undergone coronary artery bypass twice and all grafts had been
      confirmed to be angiographically intact at three and a half years prior. Coronary
      angiography revealed that a pseudoaneurysm derived from around the proximal
      ascending aortic anastomosis of the saphenous vein graft that connected to the
      left anterior descending branch and #4-atrioventricular branch sequentially. The
      pseudoaneurysm compressed the saphenous vein graft itself. He underwent repair of
      the pseudoaneurysm through median sternotomy after left subclavian artery
      saphenous vein graft bypass utilizing a free left radial artery without
      cardiopulmonary bypass through left anterolateral thoracotomy. A 7 mm length
      longitudinal tear in the saphenous vein graft near the proximal anastomosis had
      caused the pseudoaneurysm. This tear had likely been caused by perforation by a
      catheter during coronary arteriography three and a half years ago.

PMID- 11968723
TI  - Pneumothorax manifesting primary lung cancer.
AB  - Pneumothorax is a rare lung cancer manifestation. We report 2 patients in which
      pneumothorax occurred as a first manifestation of lung cancer. Postoperative lung
      tissue examination after pneumothorax showed lung cancer by chance. One patient
      had dissemination suspected due to ruptured bulla with adenocarcinoma. Both
      immediately underwent additional lobectomy with mediastinal lymphadenectomy after
      lung cancer was diagnosed, but we detected lung cancer recurrence in the bottom
      of the pleural cavity on the same side some 11 months after radical surgery in
      the patient suspected of dissemination. We could resect it completely, followed
      by adjuvant radiotherapy. The possibility of lung cancer should thus be
      considered in pneumothorax patients, even if middle-aged.

PMID- 11968724
TI  - Infected left atrial myxoma with mitral valve endocarditis.
AB  - We report a rare case of infected left atrial myxoma associated with mitral valve
      endocarditis. The tumor and a small amount of vegetative growth on the anterior
      mitral leaflet were surgically excised. Subsequent antibiotic therapy may have
      prevented the infection from recurring. Histological findings showed myxoma cells
      embedded in mucinous stroma at the tumor base and an organized thrombus with
      bacterial colonization at the tumor tip.

PMID- 11968725
TI  - Last-intercalated node and direct lymphatic drainage into the thoracic duct from
      the thoracoabdominal viscera.
AB  - OBJECTIVE: We clarified the configuration of the mediastinal lymphatics, focusing
      on the last intercalated lymph node and the direct drainage vessel to the
      thoracic duct, based on recent anatomical findings. METHODS: We macroscopically
      observed the lymphatics during dissections of 205 cadavers in combination with
      routine histology. We also review the results of injection by other researchers.
      RESULTS: Efferent vessels draining directly into the thoracic duct or venous
      angle were frequently found in the following node groups: the right paratracheal
      node group corresponding to the last intercalated node in 98% of cadavers (201);
      the brachiocephalic angle node group in 85% of cadavers (174); the right
      recurrent nerve group in 46% (94); the left superior phrenic node group in 73%
      (150); the node group at the origin of the left common carotid artery (the
      preaortico-carotid node) in 37% (76); the pretracheal node group in 25% (51) and
      the left tracheobronchial node group in 36% (74). Last intercalated nodes
      appeared common for multiple drainage routes or regional lymphatics. These
      results were mostly consistent with injection studies by Riquet et al. Direct
      lymphatic drainage from the esophagus to the thoracic duct was observed in 19% of
      cadavers (39). Direct lymphatic drainage of lung segments to distant mediastinal
      nodes is also reviewed. The sentinel node concept is discussed in relation to the
      above observations. CONCLUSIONS: We hypothesize that the most critical sentinel
      node, if such usage is allowed, is situated as a guard for a limited specific
      route and for a common drainage route. We term it the "common terminal node".

PMID- 11968726
TI  - [Fibrous pseudotumor of the tunica vaginalis testis: a case report].
AB  - A case of fibrous pseudotumor originating from the tunica vaginalis testis is
      reported. A 42-year-old man was referred to our hospital with the complaint of
      painless nodules along his right epididymis. There was no evidence of specific
      history. Ultrasonography showed an isoechoic small mass attached to the right
      testis. Inflammatory granulomas of the right epididymis were suspected, and an
      operation was carried out. The operative appearance indicated tumors of various
      sizes originating from the tunica vaginalis testis. Tumors were resected with the
      tunica vaginalis testis. Pathological diagnosis of the tumor was a fibrous
      pseudotumor. We reviewed and discussed 33 cases of intrascrotal fibrous
      pseudotumor, including our case, in the Japanese literature.

PMID- 11968727
TI  - [A case of renal angiomyolipoma with marked cystic degeneration and
      pseudoaneurysm].
AB  - A 59-year-old woman consulted our hospital for a left renal mass which she had
      been aware of for 4 years. The tumor was in the lower portion of the left kidney.
      It was a cystic tumor whose wall was enhanced on computed tomography and magnetic
      resonance imaging. The lesion 3.0 cm in diameter, which was enhanced equally to
      the aorta, was found in a part of the wall. It was thought to be a pseudoaneurysm
      by renal angiography. We suspected a cystic renal cell carcinoma because of the
      plural feeding arteries and tumor staining, and performed left total nephrectomy.
      Pathological diagnosis was angiomyolipoma with few fat components. To our
      knowledge only 3 previous cases of renal angiomyolipoma with marked cystic
      degeneration have been reported in Japan. In all 3 cases, it was difficult in
      preoperative diagnosis to distinguish angiomyolipoma with cystic degeneration
      from cystic renal cell carcinoma complicated cyst. Moreover, this is the first
      reported case of renal angiomyolipoma with marked cystic degeneration and
      pseudoaneurysm.

PMID- 11968728
TI  - [Characteristics of various electrodes for transurethral surgery].
AB  - The characteristics of four electrodes for transurethral surgery were examined by
      resection experiments using porcine muscles. The electrodes were a loop type
      (uroloop, ENDO care), a roller type (STORZ), VAPOR CUT (STORZ) and WEDGE
      (Microvasive Co). With the stroke rate fixed at 1.2 cm/second and the electrical
      output changed to 200, 220, 240 W, the electrode was moved manually by 1 stroke
      for resection. Sections were weighed, histological changes on the cut surface
      were observed under a microscope and the excised + vaporized layer and desiccated
      layer were measured. A similar study was also made with the electrical output
      fixed at 200 W and the stroke rate changed to 0.6, 1.2, 2.4 cm/second. When the
      output was increased, the excised + vaporized layer and desiccated layer became
      deep with the roller-type. The excised + vaporized layer became deep and the
      desiccated layer tended to become deep with the UROLOOP and VAPOR CUT. No change
      in either layer was found with WEDGE. When the stroke rate was increased, both
      excised + vaporized layer and desiccated layer became shallow with VAPOR CUT, but
      only the desiccated layer became shallow with WEDGE. In conclusion, the proper
      output and stroke rate were considered to be 240 W and not more than 0.6
      cm/second with the roller-type, 220-240 W and 0.6 cm/second with VAPOR CUT and
      200 W and 1.2 cm/second with WEDGE.

PMID- 11968729
TI  - [Comparative study of operation and surveillance for patients with renal
      angiomyolipoma].
AB  - Twenty-three patients (6 men and 17 women) with renal angiomyolipoma (AML) were
      analyzed. They were divided into two groups; 9 patients in the operated group and
      14 patients in the surveillance group. The operations for AML were performed on 3
      patients suspected of having renal cancer or 6 patients with an AML more than 5
      cm in size who had some symptoms as a result of the presence of the tumor. The
      patients in the surveillance group had tumor less than 4 cm in diameter, and did
      not have any symptoms. No changes in tumor size were observed during the
      intervals between observation checkups. The male to female ratio, the average age
      and the location of AML were not significant in either group. However, the tumor
      size was significantly larger in the operated group. Thus, the tumor size is
      considered to be an important factor when deciding the necessity of surgical
      treatments for AML. Pre-operative diagnosis and treatment strategies, including
      thin-section computed tomography and selective arterial embolization for AML were
      discussed.

PMID- 11968730
TI  - [A case of long-term survival neuroblastoma with conservative therapy].
AB  - We report a case of long-term survival in a patient with neuroblastoma treated
      with conservative therapy. A 2-year-old female patient who presented with a lower
      abdominal mass was diagnosed with neuroblastoma. Resection of the tumor was not
      successful because of adhesion. Histopathological diagnosis of para-aortic lymph
      node was ganglioneuroblastoma. Postoperatively 50 Gy-radiation and chemotherapy
      were performed. At age 17, needle biopsy of the tumor was performed, and the
      histopathological diagnosis was ganglioneuroma.

PMID- 11968732
TI  - [Spontaneous rupture of a left renal artery aneurysm: a case report].
AB  - Rupture of a renal artery aneurysm is an acute surgical event associated with
      high mortality. We report a case of retroperitoneal hemorrhage from a
      spontaneously ruptured renal artery aneurysm. A 73-year-old woman complained of
      left flank and abdominal pain. She consulted our department and left
      retroperitoneal hemorrhage was recognized by abdominal computerized tomography.
      Selective left renal arteriography revealed a saccular aneurysm arising from the
      ventral branch of the renal artery, and did not show extravasation of contrast
      material from the aneurysm. Since it was difficult to remove the aneurysm with
      preservation of the involved renal unit, we performed left nephrectomy.

PMID- 11968731
TI  - [Sarcomatoid carcinoma of the renal pelvis: a case report].
AB  - A 65-year-old man visited our hospital with the complaint of left hypochondrial
      pain. Since he had left giant hydronephrosis due to ureteral stone, we performed
      left nephrectomy. Unexpectedly, macroscopic examination of the resected kidney
      revealed multiple yellowish nodules located in the renal pelvis and calyces.
      Histopathologically the nodules consisted of two pattern of malignancy,
      transitional cell carcinoma and spindle sarcomatous tumor. Immunohistochemical
      examination showed that spindle cells were stained positive for cytokeratin, and
      the final diagnosis was sarcomatoid carcinoma of left renal pelvis.
      Postoperatively, the patient underwent two courses of adjuvant chemotherapy, but
      metastases to retroperitoneal lymph nodes were noted two months after operation.
      He died of the disease eight months postoperatively.

PMID- 11968733
TI  - [Chromophobe cell renal carcinoma: a case report].
AB  - We report a case of chromophobe cell carcinoma in a 41-year-old woman who was
      admitted to our hospital because of right upper abdominal pain. We performed
      right radical nephrectomy under the diagnosis of renal cell carcinoma. The cut
      surface appearance of the tumor was homogeneous, grey beige and solid. This tumor
      was diagnosed as chromophobe cell renal carcinoma after microscopic and
      immunohistochemical studies. We report our case with reference to the relevant
      literature.

PMID- 11968734
TI  - [Renal oncocytoma with synchronous contralateral renal cell carcinoma].
AB  - A 60-year-old male was admitted with bilateral renal masses with a diameter of 50
      mm (right kidney), and 15 mm (left kidney) found incidentally by computed
      tomography. Renal angiography demonstrated neovascularization in the lower pole
      of the right kidney, but no remarkable findings in the left kidney. We could not
      deny the possibility of bilateral renal cell carcinoma. Right radical nephrectomy
      and left partial nephrectomy were performed. The histopathological finding
      revealed diagnosis of right papillary renal cell carcinoma and left oncocytoma.
      To our knowledge, this is the third case of renal oncocytoma with synchronous
      contralateral renal cell carcinoma reported in Japan.

PMID- 11968735
TI  - [Metachronous primary malignant lymphoma of the bilateral tests: a case report].
AB  - We report a case of metachronous malignant lymphoma of the bilateral testes. A 62
      year-old man presented with a mass in the right scrotal contents. Physical
      examination revealed a solid painless mass in the right scrotal contents
      measuring 4 cm in diameter. He underwent right high orchiectomy. The histological
      examination confirmed non-Hodgkin's lymphoma of diffuse, large-sized cells of the
      B cell type. Computed tomography of the abdomen revealed paracaval
      lymphandenopathy at stage IIE according to Ann Arbor classification. Chemotherapy
      was initiated with cyclophosphamide, adriamycin and vincristine. Eleven months
      after the initial operation, the patient complained of left scrotal swelling, and
      subsequently underwent left high orchiectomy. The histological examination
      revealed the same pathology as observed in the right one scrotal contents. He was
      free from recurrence at 15 months after the second operation.

PMID- 11968736
TI  - [Small cell carcinoma of the prostate successfully treated with combined
      chemotherapy and radiotherapy: a case report].
AB  - A 49-year-old man complained of dysuria and pollakisuria. The prostate was
      enlarged, and the serum level of prostate specific antigen was within the normal
      range. Under the diagnosis of benign prostatic hypertrophy, transurethral
      resection of the prostate was performed. Unexpectedly, histopathological
      examination of the resected tissues revealed pure small cell carcinoma. The serum
      level of progastrin-releasing peptide (ProGRP) was slightly elevated. The cancer
      was clinically diagnosed as stage C. Pelvic radiotherapy combined with
      chemotherapy using cisplatin (CDDP) and etoposide (VP-16) was started according
      to the treatment for limited small cell cancer of the lung. After one month, the
      serum level of ProGRP decreased to the normal range. After four months, the
      prostate was reduced in size without any findings of metastases on computed
      tomography, and prostate biopsy revealed no viable cancer cells.

PMID- 11968737
TI  - [Studies on chemotactic behaviors of Strongyloides ratti infective larvae in
      vitro and migration routes of the larvae in rat head].
AB  - For the purpose of clarifying host-finding mechanisms, the infective larvae of
      Strongyloides ratti were run on an agarose plate which had been placed various
      attractants around the larvae. They were accumulated at the sites of sodium
      compounds, serum proteins and albumins. At 20, 30, 40 hours after infection, rats
      were killed and heads were separated. They were then processed for thin section
      specimens. Larvae were found in brains, olfactory bulbs and its nerves. These
      larvae seemed to move along olfactory nerves during descending from the cranial
      cavity. Another migration study was done by whole body autoradiography after 35S
      methionine labeling for clarifying the larval pathway how to invade cranial
      cavity in the rats. They first crawled under subcutaneous region of rat and then
      accumulated at the tip of the nose. Next, they began to ascend olfactory nerves.
      They were in cranial cavity up to 20 hours after infection and then descending
      same route to nasal cavity. I don't know why they aim the cranial cavity but they
      had necessity to invade the cranial cavity and stay there for appropriate time to
      be an adult in the intestine.

PMID- 11968738
TI  - [Hydrocortisone inhibits nicotinic acetylcholine receptor response in the rat
      airway parasympathetic ganglion neurons].
AB  - The effect of hydrocortisone on neurons acutely isolated from the rat airway
      parasympathetic ganglia was investigated by using nystatin perforated-patch
      recording configuration under the voltage-clamp conditions. Acetylcholine (ACh)
      evoked inward currents in a concentration-dependent manner with a half maximum
      effective concentration (EC50) of 3.3 x 10(-5) M at a holding potential of -50
      mV. The ACh response was mimicked by nicotine, and it was inhibited by both
      mecamylamine and hexamethonium. alpha-Bungarotoxin had no effect on the ACh
      response. Hydrocortisone concentration-dependently inhibited the current induced
      by 3 x 10(-5) M ACh with a half maximum inhibitory concentration (IC50) of 2.1 x
      10(-4) M. The effect of hydrocortisone was voltage-independent. Hydrocortisone
      suppressed the maximum response of the ACh concentration-response curve,
      indicating that the inhibitory action of hydrocortisone on the nicotinic ACh
      response is non-competitive.

PMID- 11968739
TI  - [Sensory extinction phenomenon of double simultaneous stimulation: the analysis
      of consecutive stroke series with acute and unilateral lesions].
AB  - We evaluated consecutive stroke patients with an acute, unilateral lesion, in
      order to elucidate the anatomical correlates and the clinical course of sensory
      extinction phenomenon as well as its relation with unilateral spatial neglect
      (USN) and anosognosia for hemiplegia (AHP). Subjects consisted of 76 patients
      with right cerebral hemispheric lesions (RHL) and 43 with left cerebral
      hemispheric lesions (LHL). Twelve of 76 patients with RHL and 18 of 43 patients
      with LHL were excluded from this study, because of consciousness disturbance,
      aphasia, severe sensory disturbance, hemianopia, or severe dementia. All of the
      patients included in this study had an ischemic or hemorrhagic stroke, who
      admitted to our hospital within 24 hours after the onset of stroke. We repeatedly
      examined the patients to detect the presence of sensory extinction phenomenon,
      USN, and AHP from their acute to chronic stage. The incidence of extinction
      phenomenon in RHL was 33% (11/19 with cortical lesions and 10/45 with deep-seated
      lesions). When we excluded the patients with a lacunar stroke or TIA, 10 of 13
      patients with subcortical lesions had sensory extinction phenomenon. Nineteen of
      21 patients with RHL who showed sensory extinction phenomenon also accompanied
      USN, and twelve had associated AHP. The sensory extinction phenomenon disappeared
      within 20 days in 6 of 10 patients with subcortical lesions and 3 of 11 with
      cortical lesions. In contrast, three of 25 (12%) patients with LHL showed
      extinction phenomenon, the incidence being much rarer than the lesion in the
      right. Of these, two had USN and one had AHP together. All the deficits
      disappeared within 20 days after the onset of stroke in patients with LHL. Our
      studies may show that subcortical lesions present with extinction phenomenon more
      frequently than cortical lesions, although the phenomenon caused by the
      subcortical lesions of often disappear in a few weeks.

PMID- 11968740
TI  - [Analysis of regional cerebral blood flow and distribution volume in Machado
      Joseph disease by iodine-123I IMP single photon emission computed tomography].
AB  - Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia. Its
      clinical features vary greatly in different generations of the same family.
      Regional cerebral blood flow (rCBF) and distribution volume (Vd) in the pons,
      cerebellum, and cerebral cortex were measured in 12 patients with MJD by
      autoradiography (ARG) and the table look-up (TLU) method of iodine-123 IMP (123I
      IMP) single photon emission computed tomography (SPECT). Representative cases
      were as follows: A 46-year-old woman first experienced gait ataxia at age 38.
      Computed tomography (CT) and magnetic resonance imaging (MRI) showed no atrophy
      in the pons or cerebellum, but rCBF measured by the 123I-IMP SPECT ARG method
      detected hypoperfusion in the pons, and cerebellar vermis and hemisphere. A 76
      year-old woman first experienced gait ataxia at age 69. CT and MRI findings
      showed severe atrophy in the pons, and cerebellar vermis and hemisphere.
      Moreover, rCBF was decreased in the pons, whereas it was not decreased in the
      cerebellar vermis and hemisphere. In the pons of patients with MJD, rCBF was
      markedly decreased regardless of disease severity. Because this SPECT finding for
      the pons looked like a 'dot', we have called it the 'pontine dot sign'. In the
      MJD group, rCBF was significantly decreased in the pons (Student's t test, p <
      0.01) and cerebellar vermis (p < 0.05). The Vd was also significantly decreased
      in the pons (p < 0.005) in comparison with that for normal subjects. Pearson's
      correlation analysis yielded a significant relationship between the rCBF in the
      pons and age at onset (r = 0.578, p < 0.05). There was a strong correlation
      between the Vd for the pons and age at onset (r = 0.59, p < 0.05). Pearson's
      correlation analysis also showed a significant relationship between the Vd in the
      cerebellar hemispheres and International Cooperative Ataxia Rating Scale (r =
      0.644, p < 0.05). The pontine rCBFs in patients with early onset MJD, whose pons
      was not atrophic, decreased more than did those in patients with late onset MJD,
      whose pons was severely atrophic. This suggests that the SPECT findings are
      indicative of underlying neurodegenerative processes that began before the onset
      of clinical symptoms. Different processes seem to function in atrophy and the
      rCBF decrease in the pons of patients with MJD. These findings will be proved by
      the increase of the number of cases of MJD. Until now, there has been no report
      on rCBF and Vd obtained by 123I-IMP SPECT for patients with MJD identified by
      gene analysis. Our study shows that SPECT measurement of rCBF and Vd is useful
      for understanding the pathophysiology of MJD.

PMID- 11968741
TI  - [Diagnosis of Alzheimer's disease using brain SPECT with three-dimensional
      stereotactic surface projections].
AB  - We compared the diagnostic usefulness of three-dimensional stereotactic surface
      projection (3D-SSP) with that of standard transaxial images in brain SPECT in
      patients with Alzheimer's disease (AD). The subjects consisted of 69 patients
      with AD and 60 patients with non-AD, including vascular dementia, Parkinson's
      disease with dementia, frontotemporal dementia, other dementing diseases and
      neuropsychiatric diseases. Standard transaxial section and 3D-SSP SPECT images
      with N-isopropyl-p-[123I] iodoamphetamine were blindly interpreted by three
      examiners and were classified into the following three patterns: typical AD,
      atypical AD, and not indicative AD patterns. The 3D-SSP images demonstrated
      reductions of cerebral blood flow in the parieto-temporal association cortex and
      posterior cingulate gyrus more clearly and easily than the standard transaxial
      images. The diagnostic sensitivity and specificity were 93% and 85% with 3D-SSP
      and 83% and 82% with standard transaxial section respectively. 3D-SSP was
      especially useful for early or atypical AD which showed no characteristic
      perfusion abnormalities on standard transaxial images. These results suggest that
      SPECT with 3D-SSP provides an sensitive as well as accurate tool for the
      diagnosis of AD.

PMID- 11968742
TI  - [A case of untreated systemic lupus erythematosus presenting with listerial
      meningitis].
AB  - A fourty-year-old woman suffered from meningitis and sepsis of Listeria
      monocytogenes, after presenting with several early symptoms from systemic lupus
      erythematosus (SLE). Listeriosis often causes central nervous system infection
      with relatively high mortality rate. This infection commonly affects patients
      with predisposing factor, such as immunosuppression. According to the previous
      reports, all of the previous reports, all of listeriosis with SLE received
      immunosuppressive therapy. To the best of our knowledge, no case of listeriosis
      has ever been reported in SLE patients without medication to SLE, although most
      of the previously reported cases of listeriosis with collagen disease accompanied
      SLE. We presume that suppression of T cell-mediated immunity, which is
      characteristic of SLE, plays a role as a predisposing factor in listerial
      infection.

PMID- 11968743
TI  - [Clinical features of a senior patient with Williams syndrome].
AB  - We experienced a case of 62-year-old woman who was admitted for the evaluation of
      her trembling hands. She was diagnosed as Williams syndrome (WS) by fluorescent
      in situ hybridization (FISH) analysis. She was short in stature, had a
      characteristic face and moderate mental retardation, whereas she was talkative
      and gregarious. She also presented impaired visuospatial cognition, cerebellar
      ataxia and tremor like involuntary movement of the hands. No remarkable
      abnormality is noted in MRI of the brain. MRA study of the brain revealed the
      arteriosclerotic vascular change, such as elongation of basilar artery and
      dilatation of bilateral carotid arteries. Heterozygous microdeletion of
      chromosome 7q11.23 of this patient is typical for WS, the delction including
      elastin (ELN) and LIMK 1 gene. Although she was complicated by diabetes mellitus
      and hyperlipidemia, she had no cardiovascular abnormalities like supravalvular
      aortic stenosis (SVAS), and survived to her age in good condition. The tremor
      like involuntary movement disappeared after her discharge and its mechanism
      remains to be elucidated.

PMID- 11968744
TI  - [A patient with myopathy due to preclinical Cushing syndrome].
AB  - A 57 year-old man with a history of diabetes mellitus was admitted to our
      hospital for the complaint of slowly progressive muscle weakness involving
      proximal limbs and head dropping. His serum CK level was within normal range, and
      muscle biopsy showed no inflammatory changes. To rule out myasthenia gravis,
      computerized tomography was done for the detection of thymoma, and detected an
      adrenal tumor in stead. He was not over-weighted, and his morning plasma levels
      of ACTH and cortisol were within normal ranges. Additional hormonal examinations
      revealed daily autonomous hypersecretion of cortisol. He received diagnosis of
      preclinical Cushing syndrome. After resection of the tumor, muscle weakness
      improved and his diabetes mellitus was controlled better. The muscle symptoms
      seem to be related with steroid myopathy. Preclinical Cushing syndrome should be
      included as a differential diagnosis for myopathy of unknown etiology.

PMID- 11968746
TI  - [A case of cavernous sinus syndrome following a mycotic aneurysm of extracranial
      carotid artery].
AB  - A 66-year-old man was admitted to our department with left abducens palsy and
      pain in the territory of the left trigeminal nerve. He had a history of left
      mandibular osteomyelitis that had been treated for five years in the dental
      department. However, the osteomyelitis was resistant to therapy. Two months
      before this admission, he had an infectious aneurysm of the left extracranial
      carotid artery with occlusion. On admission, the ESR was 140 mm/hour. P-ANCA and
      antinuclear antibody were negative. Lumbar puncture revealed elevated cell counts
      (43% neutrophils) and protein. Microbiological studies were negative. Cranial MR
      images showed an enhanced lesion in the left cavernous sinus. His condition
      gradually improved with high dose of penicillin and low dose of corticosteroid.
      However, he died of pulmonary embolism after 81 days. At autopsy, the left
      extracranial carotid aneurysm was highly fibrose. The left CCA, ICA, and ECA were
      occluded from the origin of the left common carotid artery to the ICA in the
      cavernous sinus. There were also fibrosis, hemosiderin, and macrophages around
      these arteries, and parts of these arteries were destroyed. The left cavernous
      sinus lesion was also highly fibrose. These pathological findings indicated that
      there was old inflammation around the left extracranial carotid aneurysm, left
      carotid artery, and left cavernous sinus. We believe that the left cavernous
      sinus syndrome in our patient was caused by left carotid artery vasculitis
      induced by the left infectious extracranial carotid aneurysm. We also believe
      that this infectious aneurysm was caused by the left mandibular osteomyelitis.

PMID- 11968745
TI  - [A case of Japanese encephalitis presenting with unilateral lesions in diffusion
      weighted MRI].
AB  - We report the findings of diffusion-weighted MRI (DWI) taken serially in a
      patient with Japanese encephalitis (JE). The patient was a 43-year-old woman
      presenting with headache, high fever and consciousness disturbance. The diagnosis
      of JE was made based on more than fourfold elevation of serum complement fixation
      antibody titer for JE virus in the convalescent phase of illness. The DWI on the
      second day of illness (Day-2) disclosed high-signal intensity lesions in the left
      thalamus, substantia nigra and frontal lobe cortex. The signal intensity of these
      lesions on the DWI increased on Day-3 but gradually decreased thereafter and
      normalized on Day-28. The improvement of the DWI findings was paralleled with
      that of the consciousness level and the cell number and neuron specific enolase
      concentration in the CSF, suggesting that DWI is useful for evaluation of the
      disease activity in JE. The lesions in the brain suffering from Japanese
      encephalitis are usually bilateral and diffuse. To our knowledge, this is the
      first report of JE presenting with unilateral lesions on MRI, of which
      phathomechanism remains to be elucidated.

PMID- 11968747
TI  - [Skeletal muscle pathology of chronic graft versus host disease accompanied with
      myositis, affecting predominantly respiratory and distal muscles, and
      hemosiderosis].
AB  - We report the muscle pathology in a 43-year-old woman who died of chronic graft
      versus host disease (GVHD) complicated by myositis and systemic transfusional
      hemosiderosis, after an allogeneic bone marrow transplantation and a donor
      leukocyte transfusion for acute myelogenous leukemia. Despite cyclosporin A
      treatment, fatal ventilatory failure progressed while she was still ambulant.
      Autopsy revealed the presence of chronic GVHD mildly involving the liver, skin,
      pericardium, pancreas, and salivary glands, in addition to skeletal muscles.
      Myopathic changes with mild inflammation and prominent iron deposition were found
      in the tibialis anterior muscle and, to a lesser degree, in the diaphragm and the
      intercostal muscle. There were iron deposits in both macrophages and sarcoplasm
      in the tibialis anterior. The iliopsoas and pectoralis major muscles showed
      prominent type 2 fiber atrophy; inflammation and iron deposition were minimal in
      the iliopsoas, but none in the pectoralis. Although we ascribed respiratory
      failure largely to GVHD myositis, weakness of the lower leg appeared to be
      aggravated by iron deposition superimposing the underlying GVHD myositis.

PMID- 11968748
TI  - [Spontaneous improvement of subacute exacerbation in a case of sensory ataxic
      neuropathy associated with Sjogren's syndrome].
AB  - We reported a 66-year-old man with Sjogren's syndrome (sicca syndrome) presenting
      a sensory ataxic neuropathy, which showed spontaneous remission. He developed
      difficulty in standing and walking during recent several months. Neurological
      examinations showed sensory ataxia with areflexia in all extremities and mild
      distal-dominant decrease in the superficial sensation. Laboratory examinations of
      blood, urine, and cerebrospinal fluid were all unremarkable; the blood levels of
      vitamin B1, B2, B6 and B12 were low normal. Sensory nerve action potentials and
      somatosensory evoked potentials were absent. Cervical cord MRI revealed no
      abnormal signals. Severe loss of myelinated fibers and scattered myelin ovoids
      were seen in sural nerve biopsy. Tentative diagnosis at admission was subacute
      sensory neuropathy associated with malignancy. Screening examinations for
      malignancy were undertaken and all revealed negative. Because of coexisting sicca
      symptoms and positive Shirmer test (0 mm), a lip biopsy was performed and a
      diagnosis of Sjogren's syndrome was confirmed. Sensory ataxia improved gradually.
      Two years later, blood B1 levels were low but he remained able to walk. This case
      is an uncommon example of spontaneous symptomatic remission in sensory ataxic
      neuropathy associated with Sjogren's syndrome.

PMID- 11968749
TI  - [A case of atopic myelitis in the area other than Kyushu Island].
AB  - A case of acute myelitis associated with atopic dermatitis, hyperIgEemia and mite
      antigen specific IgE was reported. A 22-year old woman with a history of atopic
      dermatitis since her childhood began to have numbness in her legs, which extended
      upward to her upper part of chest in four days. Neurological examination revealed
      Lhermitte's sign, moderate disturbance of superficial and deep sensation below
      the Th4 level, and sensory ataxia. She also showed exaggerated deep tendon
      reflexes in the upper extremities and urinary difficulty. MRI studies revealed an
      intramedullary T1-low, T2-high lesions without Gd-DTPA contrast enhancement in
      the posterior part of the cervical spinal cord at C3 level. The laboratory
      examination revealed normal CSF, and the elevated level of serum IgE and mite
      antigen-specific IgE in sera. We conclude that this case is thought to be atopic
      myelitis, which was reported as acute myelitis associated with hyperIgEemia and
      atopic dermatitis proposed by Kira et al. This is the first report of a case
      outside of Kyushu area in Japan.

PMID- 11968750
TI  - [A case of Guillain-Barre syndrome after Campylobacter jejuni enterocolitis: anti
      ganglioside antibody levels with or without Guillain-Barre syndrome].
AB  - A 38-year old man developed enterocolitis one day after he had ingested raw
      chicken. Nine days later, his grip strength weakened. Eleven days later, he was
      admitted to our hospital with weakness of four limbs, dysphagia and dysarthria.
      Serum anti-Campylobacter jejuni antibody and anti-ganglioside antibodies (GM1,
      GD1a, GD1b, GalNAc-GD1a) were positive, and motor action potentials were not
      evoked at all extremities. He was diagnosed as having Guillain-Barre syndrome.
      After receiving immune absorption therapy and plasma exchange therapy, the
      patient improved. Another person who had also consumed the same raw chicken
      developed colitis only. Five weeks later, the anti-GalNAc-GD1a-IgG antibody
      titers (O.D. 490 nm) of the patient and the other man who developed colitis were
      0.324 and 0.118, respectively. It was suggested that the pathogenesis of Guillain
      Barre syndrome after Campylobacter jejuni enterocolitis may be related to the
      type and titer of anti-ganglioside antibodies and also to the sensitivity of the
      individual.

PMID- 11968751
TI  - [A case of Churg-Strauss syndrome after corticosteroid withdrawal manifesting
      mononeuritis multiplex and gastrointestinal perforations].
AB  - We report a case of a 70-year-old man who developed Churg-Strauss syndrome (CSS),
      diagnosed by characteristic histological findings, clinical presentations of
      mononeuritis multiplex, and multiple small intestinal ulcers with perforations,
      after discontinuation of corticosteroid therapy. The patient had developed asthma
      at age of 45, treated with oral prednisolone (10-20 mg daily) from that time. At
      the age of 70 he developed pneumonia. The condition responded to antibiotics, and
      the corticosteroid was quickly tapered and discontinued. He was never given
      leukotriene receptor antagonists during the course of treatment. Approximately
      two weeks after discontinuation of steroid therapy, he developed severe abdominal
      pain and mononeuritis multiplex, confirmed by nerve conduction studies.
      Laboratory evaluation revealed an eosinophil count of 30,450/microliter, and P
      antineutrophil cytoplasmic antibody (ANCA) was positive. An abdominal CT scan
      revealed free air in the abdominal cavity. Laparotomy revealed multiple small
      intestinal ulcers with perforations. Histologic examination of the intestine
      showed eosinophilic vasculitis and fibrinoid necrosis. Treatment with systemic
      corticosteroid (prednisolone 60 mg daily) led to a clinical improvement of
      neurological and gastroenterological deficits. The prednisolone dose was tapered
      to 20 mg daily without disease flares. Recently, there have been several reports
      of CSS that manifested after withdrawal of steroid therapy. CSS can be
      precipitated in patients with adult-onset, steroid-dependent bronchial asthma
      after corticosteroid withdrawal.

PMID- 11968752
TI  - [A patient with neuroborreliosis presenting gadolinium-enhanced MRI lesions in
      bilateral facial nerves].
AB  - We report a 33-year-old man with bilateral facial paralysis due to
      neuroborreliosis. About three weeks after rhinorrhea and fever lasting four days,
      he noticed fatigue in the legs and paresthesia in all four extremities. Another
      week later, he developed paresthesia in his tongue and bilateral facial muscle
      weakness, and was admitted to our hospital. On admission, neurological
      examination revealed moderate bilateral facial muscle weakness, mild paresthesia
      in the tongue and four extremities, and decreased Achilles tendon reflex
      bilaterally. Mild pleocytosis and increased protein were found in the
      cerebrospinal fluid (CSF). IgM antibodies that reacted with the antigens of
      Borrelia garinii and Borrelia afzelii were found in his serum. Clinically and
      serologically, he was thus diagnosed as having neuroborreliosis. Brain MRI
      revealed gadolinium-enhanced lesions of the bilateral facial nerves in the facial
      nerve canal portion. After three weeks of treatment with 100 mg/day doxycycline
      and 2 g/day ceftriaxone sodium, his symptoms and CSF abnormalities were rapidly
      improved. Although facial nerve paralysis is a major symptom of neuroborreliosis,
      the present report is the first to detect the inflammatory lesions of the facial
      nerves in the facial nerve canal portion by MRI.

PMID- 11968754
TI  - [CADASIL associated with alopecia and lumbar herniated disk].

PMID- 11968753
TI  - [A patient who developed dermatomyositis during the 1st trimester of gestation
      and improved after abortion].
AB  - This patient was a 30-year-old woman who was in the 8th week of her first
      pregnancy with three embryos. She developed fever, myalgia and weakness of the
      proximal muscles, and erythema of the face, dorsal aspects of elbows, and knees.
      Routine blood examinations showed elevated serum CK. Immunologically, an anti-Jo
      1 antibody was positive. Skin biopsy revealed mucinosis and edema in the
      superficial layer of the corium, and liquid alternation in the basal layer of the
      epidermis. From these findings, this patient was diagnosed as having
      dermatomyositis. She was placed on oral prednisolone (80 mg daily), but her
      clinical symptoms did not improve and all fetuses died by the 11th week of
      gestation. Then she underwent dilation and curettage and after this operation her
      disease rapidly subsided. It seemed that fetuses were causatively related to the
      development of dermatomyositis possibly by changing maternal immune condition.
      There were six reported cases with dermatomyositis/polymyositis who developed
      during the first trimester of gestation. Four of these 6 patients were treated
      with oral steroid; however, only one patient ended in normal delivery. More
      aggressive therapy, other than corticosteroid, may be required to improve fetal
      prognosis.

PMID- 11968756
TI  - [Gene manipulation in the field of surgery].
AB  - Recent advances in molecular biology have led to expectations for the use of gene
      therapy or gene manipulation as a radical treatment strategy. I described the
      research projects and results, in the field of organ transplantation and cancer
      treatment in which we have been involved.

PMID- 11968757
TI  - [Molecular biology-based surgery for the future progress of cancer treatment].
AB  - The basic surgical procedures for all diseases and organs were established by the
      end of the 20th century. However, the results of surgical treatment in cancer
      patients are still unsatisfactory. Despite radical resection based on the
      conventional diagnostic system for cancer metastases, disease recurrence and
      relapse are major problems in the clinical field of oncology. Standarized therapy
      without understanding the biology of tumors has not contributed significantly to
      cancer patients. Here, we propose that molecular biology-based surgery, or a
      strategy of surgical oncology based on information obtained from new molecular
      techniques should be urgently established to improve the management of cancer
      patients.

PMID- 11968758
TI  - [Neoadjuvant chemoradiotherapy in patients with surgically treated T4 esophageal
      squamous cell carcinnoma].
AB  - BACKGROUND: Esophageal cancer carries one of the poorest prognoses among
      digestive tract malignancies. Recent evidence suggests that the addition of
      nonsurgical treatment to surgery may improve resection rates, reduce the risk of
      recurrence, and improve survival. METHODS: From August 1989 to December 2000, 69
      patients with locally advanced (T4) esophageal squamous cell carcinoma were
      treated with combined 5-fluorouracil, cisplatin, and radiotherapy. Operative
      resections were achieved in 35 of 69 patients during surgical explorations.
      Preoperative chemoradiotherapy for patients with T4 esophageal cancer was
      effective in 27 of 35 (CR + PR: 77.1%), and a complete response (no tumor found
      in the surgical specimens) was observed in 7 of 35 (20.0%). Five-year survival
      was prolonged significantly based on the histological response rate (CR: 71%, PR:
      32%, NC: 0%). The p-53 gene mutation was detected by the PCR-SSCP method. DNA
      sequences were determined for DNA fragments with shifted peaks by SSCP methods.
      CONCLUSION: Radical esophagectomy after concomitant chemoradiotherapy is
      potentially curative for locally advanced esophageal carcinoma, and the p-53
      genetic abnormality might be a good marker for chemoradiosensitivity
      (histological poor response) in patients with T4 esophageal cancer.

PMID- 11968759
TI  - [Current strategy to cure pancreatic cancer].
AB  - For more than a decade extensive retroperitoneal dissection, chemotherapy, or
      radiotherapy has not prolonged the survival of patients with pancreatic cancer.
      Two prospective randomized studies addressing the clinical significance of
      extensive dissection or pancreatic resection for advanced cancer are now in
      progress. Nonetheless, at present, resection offers the patient the only
      possibility of cure. Although the diagnosis of curable pancreatic cancer is
      difficult, recent evidences have given a few hints. The first is pancreatic duct
      dilatation caused by cancerous stricture. The second is diabetes as a sign of
      pancreatic cancer. Our prospective pancreatographic screening of diabetic
      patients selected by our criteria(Table 1) revealed 7 cancers in 98
      patients(7.1%). Within 3 years from diagnosis, the prevalence was 15%. Although
      the 7 cancers were advanced, this suggests that earlier examinations in diabetic
      patients may possibly lead to earlier diagnosis. The third is a small cystic
      lesion as a sentinel of pancreatic cancer. Endoscopic retrograde
      cholangiopancreatography with cytology of the pancreatic juice may show the
      presence of in situ cancer in patients with a pancreatic cyst. At the moment,
      careful checks for the presence of these hints seem to be the only strategy to
      offer a chance for cure to patients with pancreatic cancer.

PMID- 11968760
TI  - [An ideal liver support system and xenotransplantation].
AB  - Currently, the rapid increase in the number of candidates for orthotopic liver
      transplantation has resulted in a shortage of donor organs and, especially for
      fulminant hepatic failure, an urgent need for transplantations. Thus the need for
      a liver support system as a "bridge" before liver transplantation is also urgent,
      as is the need for treatment of reversible acute liver disease. Various liver
      support systems have been proposed, for example, cross-circulation systems,
      extracorporeal liver support systems, hemodialysis, and hemadsorption, but these
      are not considered to function sufficiently. Demetriou's system, Sussman's
      system, and Gerlach's system have reached clinical trials. The ideal liver
      support system should have significant metabolic capacity, the ability to be used
      in continuous treatment, simplicity of use, biocompatibility, ready availability,
      consistency, economy, and safety from viral infection, but no system meets all of
      these criteria.

PMID- 11968761
TI  - [Division of gastroenterological surgery].
AB  - Regenerative medicine and artificial organs are fields of development in the 21st
      century. Various stem cells are found in many organs, and it is expected that
      medical treatment with the induction of regeneration in vivo and ex vivo using
      growth factors will be available. On the other hand, human embryonic stem cell
      lines (ES cells), which can transform themselves into any cell in the body, have
      been established. Since the development of cloning technology, the production of
      "individual ES cells" is also no longer only a dream. At the same time, the use
      of human cloned embryos entails important ethical and social considerations. As
      is well known, although artificial organs are not perfect, they can substitute
      for the functions of the kidney and heart. In the future, miniaturization and
      advanced features can be expected by application of microtechnologies. To execute
      various functions of synthesis and metabolic processes, for example, with an
      artificial liver, hybrid artificial organs incorporating cell functions are in
      development. We should not use animal cells because of unknown infectious
      diseases. It is therefore desirable to use human cells by the application of
      regenerative medicine or genetic engineering. Because both regenerative medicine
      and artificial organs can be expected to change medical treatment dramatically in
      the 21st century, steady efforts to clarify cell functions and molecular
      mechanisms will be required, as well as addressing ethical/social considerations.

PMID- 11968762
TI  - [Problems and reformation of the board of medical specialties in Japan].
AB  - The Board of Medical Specialties, which is closely related to postgraduate
      training in Japan, including the Board of Surgery, has serious defects in its
      system because it has developed on its own initiative and has been administered
      by a medical society. Many of the public are not aware of its existence, and its
      workings are difficult for them to understand. In the past 20 years, the
      Organization for the Board of Medical Societies (tentative English translation)
      has aimed to ensure sound development of the Board of Medical Specialties. Along
      with the activities of this organization, the Japan Surgical Society also decided
      to improve and reform its Board of Surgery and the boards of its subspecialties.
      The management, examination, and evaluation of the board system should be under
      the control of a third party separate from the medical societies. The ideal Board
      of Medical Specialties should not only foster gifted physicians but also benefit
      the public, communities, and medical societies.

PMID- 11968763
TI  - [State of the art and problems in medical safety management].
AB  - The principle of medical safety management is to build a safe medical system that
      is equipped to prevent patient injuries due to medical errors occurring in it and
      not to attribute them only to individual responsibility. Methodologically, this
      means identifying and reducing the potential risk of medical errors by systematic
      reporting and tracking of errors and near misses. According to some major
      clinical studies on medical malpractice in the USA, the incidence of medical
      accidents is reported to be 3-5%, 30% of which were due to negligence, and 7-14%
      resulted in patients' deaths. It is also reported that 66% of the medical
      accidents occurred in surgical specialties and 45% were related to surgeries,
      which were shown to have the highest risk of medical accidents. On the other
      hand, according to a nationwide survey on reported errors and near misses in
      Japan, 50% were related to drugs, especially injections. Other major causes
      reported in the study were manipulation and management of medical instruments,
      downfalls of patients, and aspiration. These safety problems listed above were
      shown to compose 95% of all of medical errors and near misses. To establish a
      rational safety management system, it is necessary to develop research methods
      appropriate for the study of medical errors, which facilitate clinical research,
      and can be expected to yield sufficient scientific data. A generalized guideline
      for voluntary reporting of patients' deaths and injuries due to medical errors,
      in relation to Article 21 of the Doctors' Law should be established. However, for
      essential improvement of transparency and accountability in medicine, it is
      necessary to set up a new specialized institute to accept reports on medical
      errors, give hospitals advice for a safer medical system, and disclose
      information on medical errors. Moreover, such an institute should continue to
      study medical safety by analyzing nationwide reports of medical errors and near
      misses. For the latter purpose, legal protection of the disclosure of information
      must be assured.

PMID- 11968764
TI  - [Maintaining safety management in the field of surgery].
AB  - Due to an increase in the number of medical accidents and medical conflicts, the
      administration of medical safety has recently introduced the following measures
      to cope with this situation; the process and the structure (reason) of error is
      analyzed based upon evidential facts, the origin of the errors is analyzed mainly
      in terms of teamwork and specialized medicine and structures rather than in terms
      of the ability of the individual, and the strategy against medical errors has
      been converted from aspects of management to prevention. The comprehensive
      strategy pursued now covers the field of social medical systems in addition to
      medical institutions. However, the judicial decisions in 90% of medical conflicts
      ruled that these were caused by the lack of knowledge and skills of the medical
      doctor, and a survey performed by the Japan Medical Association based on medical
      insurance research has reported incidences of repeated medical errors by the same
      physician. This has led to some criticism from the victim's viewpoint that
      insufficient administration of medical quality result in increased numbers of
      accidents which are due to repeated medical errors, under "legal" medical
      practice by "incompetent" doctors who should have been systematically reeducated
      or dismissed. In recent years, several societies and research groups of the
      Ministry of Health, Labour and Welfare have constructed medical guidelines based
      on evidence-based medicine techniques. The introduction of the clinical pathway
      offers the medical team access to information, directed to the appropriate roles,
      which may be helpful in performing constant safety checks. This medical check
      method that involves the patient's input will also contribute to the prevention
      of medical errors and promotion of safety.

PMID- 11968765
TI  - [Surgery of the liver and pancreas in Japan--message to the special symposium
      commemorating Dr. Ichio Honjo].
AB  - About half a century ago, Ichio Honjo performed successful right hepatic
      lobectomy following ligation of the right hepatic artery and the right branch of
      the portal vein. That was the world's first successful case of right hepatic
      lobectomy with preliminary hilar ligation of the right branches of both the
      hepatic artery and portal vein. In the same year, Honjo carried out a total
      pancreatectomy for pancreatic cancer for the first time in Japan. Since then,
      marked progress in the surgical fields of the liver and pancreas has been made
      and appear to have nearly reached the pinnacle. Surgeons in the late half of the
      20th century attempted to extend operative interventions and expand surgical
      fields while devoting themselves to treating incurable diseases. Therefore the
      period may be called the "challenging era." We are entering the era of evaluation
      and selection of the procedures most suitable to both the disease stage and each
      individual patient.

PMID- 11968767
TI  - [Understanding of AIDS and its control].

PMID- 11968769
TI  - [Molecular epidemiology of HIV: principle and its application].
AB  - The accumulation of full-length HIV genome sequences in the different regions of
      the world led to a new view to the HIV pandemic. It is recognized that subtypes
      and intersubtype recombinants are equally important in the pandemic. In this
      article, we will discuss the latest findings on molecular epidemiology of HIV and
      the related subjects.

PMID- 11968768
TI  - [Current situation and perspectives of HIV-1 epidemic in the world and in Japan].
AB  - Global HIV-1 epidemic has evolved into a human security issue rather than one of
      the health problems, particularly in sub-Saharan Africa. HIV-1 epidemic is also
      growing in Asia, being projected to soon explode in the world largest countries,
      India and China. Japan is at stake of future epidemic, because of the possible
      influence of the epidemic in neighboring countries and more because unprotected
      sex is clearly prevailing among Japanese youth. This is reflected in the sudden
      and synchronized increase in STD and induced abortion among teenagers and
      endorsed by the recent nationwide sexual behavior surveys that showed sexual
      behavior of the youth being highly networked and unprotected. Prevention programs
      should be soon developed and implemented in Japan.

PMID- 11968770
TI  - [Molecular mechanism of HIV-1 replication].
AB  - Host factors that associate retrovirus replication also play an important role in
      regulating cellular physiological conditions. Therefore, a discovery of HIV
      related cellular proteins might open up understanding mechanisms for essential
      cellular machinery. Recent advances in biotechnology have shed new light on the
      molecular mechanism of HIV replication. We choose three topics about HIV
      replication and discuss them; a role of ubiquitin and vacuolar protein sorting
      pathway during virus budding, new players, integrase and central DNA flap, that
      regulate the translocation of preintegration complex into nucleus, and a
      relationship between basic model for core formation and fullerene molecule.

PMID- 11968771
TI  - [HIV-suppressive factors].
AB  - A number of host and microbial factors have been shown to modulate HIV-1
      infection. Their inhibitory effects are either HIV-specific or non-specific, and
      involve many different kinds of mechanisms. Among anti-HIV host factors are
      natural ligands or natural antibodies to HIV coreceptors, anti-inflammatory
      cytokines, interferons and several body fluid components (such as lactoferrin and
      prostaglandins). Microbial pathogens/factors that may suppress HIV-1 infection
      include lipopolysaccharide, scrub-typhus rickettsia, human herpesviruses-6 or -7,
      and GB virus C. While simple application of these HIV-suppressive factors for HIV
      infected individuals is not realistic, investigation of mechanisms involved may
      lead to better understanding of HIV pathogenesis and help establish novel anti
      HIV strategy.

PMID- 11968772
TI  - [The function of accessory genes of HIV-1].
AB  - Human immunodeficiency virus type 1 (HIV-1) has 4 auxiliary genes, vpr, vpu, nef,
      and vif, which are dispensable for viral replication in vitro. However, many
      studies with animal model revealed that these genes play important roles on the
      viral replication and the development of AIDS in vivo through many complicated
      mechanisms. Although several key factors involved in the function have been
      identified, further studies are required for the complete understandings of the
      action mechanisms. The elucidation of the function of the auxiliary genes on
      molecular bases leads to the discovery of new therapeutic strategies against HIV
      and the understanding of basic cellular mechanisms. In this review, we summarize
      new observations mainly about the interactions between auxiliary genes and host
      cell functions.

PMID- 11968773
TI  - [Chemokine receptors and HIV-1 infection].
AB  - Chemokines are now known to function as regulatory molecules in leukocyte
      maturation, in traffic and homing of lymphocytes, and in the development of
      lymphoid tissues. Besides these functions in the immune system, certain chemokine
      receptors also function as co-receptors for human immunodeficiency virus type-1
      (HIV-1) entry into CD4+ lymphocytes. CCR5 and CXCR4 are the major co-receptors
      for macrophage tropic and T-cell line tropic viral isolates, respectively. Here,
      we review recent studies on the relationship between chemokine receptors and HIV
      1 infection. Elucidating the roles that chemokines and chemokine receptors play
      in the course of HIV-1 infection may substantially enhance our understanding on
      the HIV-1 pathogenesis, and perhaps help the discovery of drug candidates for
      therapeutic intervention of HIV infection.

PMID- 11968774
TI  - [Diagnostic criteria for HIV/AIDS in Japan].
AB  - In Japan, criteria for the diagnosis of HIV infection and AIDS have been revised
      in 1999. For the diagnosis of HIV infection, HIV-positivity has to be confirmed
      by western blot test or nucleic acid tests such as PCR for HIV when the results
      of screening tests for anti-HIV antibodies (ELISA) are positive. Diagnosis of
      AIDS can be made when HIV-infected persons show any one of 23 indicator diseases.
      Criteria for the diagnosis of these 23 diseases are described. The indicator
      disease most frequently seen in Japan is Pneumocystis carinii pneumonia followed
      by candidiasis, cytomegalovirus infection, tuberculosis and non-tuberculous
      mycobacteriosis in this order. The number of new cases of AIDS is still
      increasing every year.

PMID- 11968775
TI  - [Detection and quantification of HIV-1 provirus provides a prognostic marker for
      the therapy-monitoring].
AB  - By the effective application of highly active antiretroviral therapy (HAART), the
      plasma HIV-1 RNA level can be dramatically suppressed to below the detectable
      level in a short period. As the amount of total HIV-1 DNA in peripheral CD4+
      cells sharply decline in the first phase of the treatment in accordance with the
      decline of HIV-1 RNA, total HIV-1 DNA, mainly containing the unintegrated form,
      can be a useful marker for therapy-monitoring just as HIV-1 RNA. In the next
      phase, after the transcription and reverse transcription of HIV-1 are profoundly
      inhibited by continuing HAART, the mass of the latent HIV-1 reservoir can be
      quantified by measuring the amount of total HIV-1 DNA which mainly reflects the
      integrated HIV-1 provirus in this phase.

PMID- 11968776
TI  - [Clinical utility of drug resistance testing].
AB  - Emergence of drug resistant HIV-1 is one of the major causes of the anti
      retrovirus treatment failure. There are two types of clinical tests to identify
      the drug resistance. One is nucleotide sequencing of the drug target genomes
      (genotyping) and the other is measuring drug susceptibility of patient derived
      HIV-1 in vitro (phenotyping). Several retrospective studies have shown
      correlation between drug resistance test results and treatment outcome. The
      numbers of prospective randomized cohort studies have been also performed to
      clear the usefulness of drug resistance genotyping and phenotyping. Most of these
      studies have shown significant decrease of plasma virus level in the cases
      treated with genotypic and/or phenotypic guides. These results clearly support
      usefulness of genotyping and phenotyping in managing anti-HIV-1 treatment.

PMID- 11968777
TI  - [Recent advances in molecular pathogenesis of HIV infection].
AB  - Highly active anti-retroviral therapy (HAART) dramatically improves the prognosis
      of individuals infected with HIV, and changes the pathophysiology of HIV
      infection. However, the eradication of HIV has not been achieved by HAART due to
      presence of reservoir cells. More potent strategy of therapy against HIV is
      needed for further suppression of the replication and eradication of reservoirs.
      The recent advances about molecular pathogenesis of HIV infection are reviewed in
      this paper, that leads to discovery of the new molecular targets of anti-HIV
      drugs.

PMID- 11968778
TI  - [Protective immunity against HIV infection].
AB  - The clinical manifestation of HIV infection varies among HIV-exposed individuals.
      Most HIV infected people will develop AIDS after 8-10-yr exposure. However, long
      term nonprogressors (LTNP) can remain asymptomatic and keep normal CD4 cell in
      the absence of treatment even after more than 10-yr of infection. In addition
      there are some exposed yet uninfected individuals (EU) despite repeated exposure
      of HIV among high risk group. Although HIV-specific IgG antibodies and small
      amount of viral RNA could be observed among the former LTNP group, no HIV
      specific IgG and virions could be detected in the latter EU cohort. In contrast,
      the fact that cellular immune responses, in particular HIV-specific CD8+ CTL
      immunity could be seen in both groups strongly indicates their importance for the
      establishment of protective immunity. Together with the cellular immunity, the
      effect of mucosal immune components such as secretory IgA, gamma delta T cells
      and dendritic cells toward HIV infection will be discussed.

PMID- 11968779
TI  - [Host genetic polymorphisms in the pathogenesis of HIV-1 disease].
AB  - HIV-1 infection is generally characterized by a long-term, chronic disease course
      gradually progressing to AIDS. However, there are a few but strikingly different
      scenarios. A small fraction of HIV-1 infections remains normal both clinically
      and immunologically over 10 years or more after seroconversion. Conversely,
      another marked fraction is featured by an extremely rapid disease progression
      taking place even within one year. Determining the host factors of these
      different disease courses would be extremely helpful for better understanding and
      control of AIDS. Here we show examples of host genetic polymorphisms, which can
      affect HIV-1 transmission and disease courses.

PMID- 11968780
TI  - [Initiation of therapy: when and what to start with?].
AB  - Introduction of HAART (highly active antiretroviral therapy) has resulted in
      dramatic reductions in AIDS-related opportunistic complications and death. We
      have faced, however, severe complications due to HAART such as lactic acidosis
      and lipodystrophy syndrome. Regimens currently employed in the treatment may be
      complex, require multiple drugs to take, difficult to tolerate owing to adverse
      effects, and decrease level of quality of life in some patients. Decisions about
      when and with what to initiate HAART must take into account the risk-benefit
      ratio associated with the therapy. In this article, issues that must be
      considered in determining timing of initiation and choice of anti-retroviral
      drugs are discussed.

PMID- 11968782
TI  - [Salvage therapy in HIV disease].
AB  - Highly active antiretroviral treatment(HAART) is very effective for Japanese
      Human immunodeficiency virus(HIV) patients in the morbidity and mortality. But
      the need for salvage therapy is related to the imperfection of current
      antiretroviral therapy. HIV-RNA load will be detectable in approximately 40% of
      non-naive HIV patients who are taking triple therapy after 1 year of follow-up.
      Treatment failure may be related to poor adherence, resistant virus and poor
      pharmacological bioavailability. This article aims at describing the strategic
      thoughts in rapid development of pathophysiological as well as clinical and drug
      related knowledge. Patient commitment, physician knowledge and an informed
      supportive environment are important to success in salvage therapy.

PMID- 11968781
TI  - [Clinical impact of combination antiretroviral therapy].
AB  - After the advent of HIV protease inhibitor in 1995, the clinical feature of HIV
      disease has been dramatically changed. Combination antiretroviral therapy
      containing protease inhibitor can suppress the viral load under the detection
      limit and recover the immune status in HIV-infected individuals. However, it
      still seems impossible to eradicate the viruses from infected individuals. They
      will have to continue the combination therapy for life with good compliance
      because incomplete viral suppression induces the resistant viruses. The clinical
      feature of opportunistic infections in HIV-infected patients has also been
      changed. In some cases, prophylaxes for Pneumocystis carinii pneumonia and
      Mycobacterium avium complex infections are not necessary after the introduction
      of combination antiretroviral therapy.

PMID- 11968783
TI  - [Challenges of the anti-retroviral therapy].
AB  - Anti-retroviral therapy has still many difficulties for the continuous viral
      suppression, although it has markedly improved the prognosis of the patients with
      HIV/AIDS. It is essential that anti-retroviral therapy requires strict adherence
      of the patients. More than 95% of adherence to have medicine is required for the
      success of the therapy. Severe and frequent adverse reactions, many pill burden,
      food restriction and patients' poor recognition to the therapy influence
      adherence. Of those, adverse reaction of the drugs is the strongest factor for
      disturbing adherence. Digestive tract symptoms such as nausea, vomiting,
      abdominal pain and/or diarrhea are common and affect to reduce adherence.
      Recently, lactic acidosis/hepatic steatosis and lipodystrophy syndrome have been
      recognized as novel and important adverse reactions with anti-retroviral
      medicines. Physicians should be aware of the importance of adherence, and assist
      the patients to improve it with multiple approaches.

PMID- 11968784
TI  - [Approach to opportunistic illness in the HAART era].
AB  - AIDS-defining opportunistic illness(OIs) are the major cause of mortality among
      persons infected with HIV. The incidences of many OIs are decreasing because of
      advances in HIV-related therapy. These decreases have been attributed to
      successful OI prophylaxis and the use of highly active antiretroviral
      therapy(HAART). Patients who have responded to HAART and have a sustained
      increase in CD4+ cell counts appear to be well protected from OIs. Thus, a
      strategy of discontinuation of chemoprophylaxis for patients whose immunity has
      improved seems logical. HAART is the most effective approach to preventing OIs.
      However, OIs are still occurring, especially when patients access care late
      during the course of disease. Prophylaxis and treatment against specific OIs
      continues to provide survival benefits even among persons who are receiving
      HAART.

PMID- 11968785
TI  - [Basic approaches to anti-HIV resistance].
AB  - Highly active antiretroviral therapy with reverse transcriptase inhibitors(RTIs)
      and protease inhibitors(PIs) has achieved high-level suppression of viral load in
      HIV-1-infected patients. However, drug-resistant HIV-1 mutants often emerge,
      resulting in treatment failure. Various research attempts have been made to
      overcome the drug-resistance. At present, more than 200 amino acid mutations that
      confer resistance to anti-HIV-1 compounds have been reported. Furthermore,
      molecular mechanisms of the resistance induced by some RTIs and PIs have been
      well understood. Novel inhibitors effective against the resistant mutants have
      recently been discovered and are under clinical trials.

PMID- 11968786
TI  - [The impact of resistance testing of HIV-1 to the HIV clinical setting in Japan].
AB  - Recently, resistance testing of HIV-1 become available to clinicians in Japan.
      Retrospective studies show that results of these tests predict the response to
      salvage therapy, and randomized, controlled clinical trials show short-term
      virologic benefits of resistance testing as a guide to selecting salvage
      regimens. But the ultimate role for resistance testing in HIV clinical practice
      is yet to be determined fully. Both phenotypic and genotypic tests have yet to be
      fully standardized. Interpretation of results is still an 'art', and access to
      testing is still limited by cost considerations. This review will describe some
      of the tools that are available for interpreting genotypic assays.

PMID- 11968787
TI  - [Development of new reverse transcriptase inhibitors].
AB  - Highly active anti-retroviral therapy(HAART) using two or more reverse
      transcriptase inhibitors(RTIs) and protease inhibitors, has dramatically improves
      the quality of life and survival of patients infected with human immunodeficiency
      virus(HIV). RTIs are categorized by their mechanism of action, into two groups,
      nucleoside(N) and non-nucleoside(NN) RTIs. However, resistant HIV variants
      against NRTIs and/or NNRTIs including multi-drug resistant, emerge after the
      prolonged therapy. To suppress the replication of such resistant variants,
      numerous anti-HIV drugs have been developed. In this review, the mechanisms of
      action and characters of the major drugs in clinical or under preclinical are
      described.

PMID- 11968788
TI  - [New HIV-1 protease inhibitors in development].
AB  - Protease inhibitors block the protease enzyme of HIV-1. When new viral particles
      break off from an infected cell, protease cuts long protein strands into the
      parts needed to assemble a mature virus. When protease is blocked, the new viral
      particles cannot mature. Protease inhibitors being tested in humans include
      Atazanavir, GW433908, L-756,423, Mozenavir(DMP-450), Tipranavir and more. Several
      firms are trying to develop a new type of protease inhibitor that will be the
      more favorable pharmacokinetic and resistance profiles compared with currently
      available drugs. We cannot expect that every one of the drugs listed in this
      paper will be successfully developed. However, it is likely that significant
      clinical advancements can be made with those that are proven to be active and
      safe for patients in need.

PMID- 11968789
TI  - [Replication inhibitors targeting early events in the HIV-1 life cycle].
AB  - Most of the compounds currently used for treatment of HIV-1 infection are reverse
      transcriptase inhibitors and protease inhibitors. Several early steps in the HIV
      1 life cycle such as virus attachment to host cell and cell-virus fusion are
      potential targets for drugs. Since most of the target molecules involved in this
      infection step are cellular, it is expected that the drug resistant mutations
      occur less frequently than those against viral enzymes. In this review, new
      inhibitors of entry and fusion are summarized that are promising.

PMID- 11968790
TI  - [Development of HIV vaccines].
AB  - An effective prophylactic vaccine should reduce frequency of new HIV infections
      in the target population and delay onset of immunodeficiency among those who
      become infected after vaccination. A variety of vaccine candidates have been
      developed, which induce neutralizing antibodies and/or cytotoxic T-lymphocytes.
      While many of those vaccine candidates exhibited some efficacy in primate model
      systems, their efficacy against natural HIV-1 infection can only be determined in
      large-scale phase III clinical trials. In this article, difficulties in HIV
      vaccine development will be discussed from scientific, technical, and business
      point of views.

PMID- 11968791
TI  - [Impact of HIV on HCV, GBV-C/HGV, and HBV infection].
AB  - To investigate influence of HIV co-infection on HCV, we examined 58 Japanese
      hemophiliacs with chronic hepatitis C(CHC) including 25 patients co-infected with
      HIV. HCV RNA levels and liver function were not affected statistically by the
      presence of HIV. Further studies are necessary to evaluate the impact of HIV on
      the prognosis of CHC in hemophiliacs. We were the first to report a beneficial
      effect of GBV-C/HGV infection on the course of HIV disease and many studies were
      confirmed our results. Discussions of these important issues such as impact of
      HIV on GBV-C/HGV and HBV have been performed in this paper.

PMID- 11968792
TI  - [Living donor liver transplantation in a patient with HIV].
AB  - Highly active anti-retroviral therapy(HAART) for human immunodeficiency
      virus(HIV) has delayed the disease progression. The advances prompted us to
      undertake liver transplantation in a 41-year-old man with hemophilia B, HIV
      infection, and hepatitis C(HCV) end-stage liver disease. The donor was the
      patient's elderly brother. His right liver was implanted by the standard method.
      Two months after the operation, interferon alfa and ribavirin were administered
      for HCV infection. HCV was eradicated two weeks after the treatment. The HIV
      viral load is persistently negative and HAART has not been started so far.
      Utilizing a organ from living relatives should be one of the options to resolve
      the concern around the utilization of a scarce public source from cadavers for
      patients who may not have an equivalent survival to HIV negative patients.

PMID- 11968793
TI  - [The current status of structured treatment interruption].
AB  - There is considerable interest in structured treatment interruption(STI), which
      has been stimulated by certain evidence that treatment interruption may boost the
      infected individual's immune response to HIV-1. There are several distinct
      settings where STI may be instituted: (i) STI for those with acute HIV-1
      infection, (ii) STI for those with chronic infection, and (iii) STI before
      switching drugs. A number of STI protocols have been evaluated and certain
      promising results have been reported in certain groups of HIV-1-infected
      individuals while viral rebound as the consequence of interruption has been seen
      in other patients and drug failure to re-suppress HIV-1 upon re-starting therapy,
      STI-associated CD4+ cell decline and viral drug resistance emergence have been
      serious concern. Currently, STI cannot be recommended in clinical settings.
      Randomized, controlled trials to determine the applicability of STI for therapy
      of HIV-1 infection are required.

PMID- 11968794
TI  - [Cost of HIV treatment in highly active antiretroviral therapy in Japan].
AB  - In a study of estimating the socio-economic impact of HIV infection in Japan in
      1999, the hospital costs of treating HIV-infected adult patients were estimated
      by clinical stage of HIV infection. A total of 608 claims for medical fee of 109
      individuals derived from 5 hospitals were examined in that study. The costs of
      treating outpatient were estimated at between 180,000 yen and 216,000 yen per
      month and 83% of the total cost was accounted for by antiretrovirals. Cost
      estimates per month for inpatient with AIDS varied from 373,000 yen for CD4+ 200
      499, to 768,000 yen for CD4+ 50-199, to 1,715,000 yen for CD4+ < 50. Compared
      with cost estimates in 1995, the outpatient costs were 2.7 to 8.6 times and the
      inpatient cost increased by 25%.

PMID- 11968795
TI  - [Recent advances of basic research and clinical application of lactoferrin as an
      antiviral reagent against chronic hepatitis C].
AB  - Hepatitis C virus(HCV), discovered in 1989, is the major causative agent of
      chronic viral hepatitis. Most patients progress to liver cirrhosis and
      hepatocellular carcinoma. In the therapy of hepatitis C, only interferon has been
      used effectively as an anti-HCV reagent in Japan, but its effectiveness is
      limited to about 30% of cases. Using human hepatocyte cell line which could
      support efficient HCV replication, we previously found that lactoferrin inhibited
      HCV infection, and demonstrated that this inhibiting activity was due to the
      interaction of lactoferrin with HCV. Further analysis found that the carboxyl
      region of lactoferrin, which partially shows amino acid sequence homology to
      human CD81, specifically bound to the HCV E2 envelope protein, and identified a
      33 amino acids as a critical binding domain of lactoferrin. On the other hand, it
      has been shown that bovine lactoferrin was effective in some patients with
      chronic hepatitis received an 8-week course of lactoferrin treatment. Further
      clinical trials showed that lactoferrin is a promising candidate for adjuvant
      therapy with interferon in patients with chronic hepatitis C.

PMID- 11968797
TI  - [The correlation between urodynamics and morphology in men with benign prostatic
      hyperplasia].
AB  - OBJECTIVE: We have the impression that the degree of obstruction was stronger in
      the patients with a middle lobe of hyperplastic nodule than in those without such
      a lobe in patients with benign prostatic hyperplasia. In the present study, we
      compared the data from a pressure-flow study (PFS) and a presence of a middle
      lobe. MATERIALS AND METHODS: A transurethral resection for benign prostatic
      hyperplasia was performed in 2,439 patients, 798 underwent PFS. The PFS findings
      and the presence of a middle lobe were compared with the following parameters,
      namely, the bladder detrusor function, the degree of obstruction, the post-voided
      residual volume, the maximum flow rate, the prostate volume and the resected
      volume. RESULTS: In the pressure-flow study, the rate of the normal bladder
      detrusor function was higher in the patients with a middle lobe than in those
      without such a lobe (71.9 versus 53.3%). The degree of obstruction was also
      stronger in the patients with a middle lobe than in those without in the patients
      with a normal bladder detrusor function (89.0 versus 79.4%). Then in the patients
      with a middle lobe, the quantity of the post-voided residual volume was greater,
      however, the maximum flow rate was lower. CONCLUSION: Most patients with a middle
      lobe demonstrate an improved voiding ability after underwent a transurethral
      resection.

PMID- 11968796
TI  - [The effects of the antagonists of muscarinic acetylcholine receptor subtypes in
      rat brain on urinary bladder contraction].
AB  - BACKGROUND: Pontine micuturition center and storage center are controlled by
      upper brain. Pharmacological and molecular biological data indicate the
      distribution of muscarinic receptor subtypes in rat brain, however, the effect of
      central muscarinic cholinergic mechanisms on the bladder activity has not been
      evaluated. We investigated the diversity of effect of each subtype in rat brain.
      METHODS: The muscarinic agents such as muscarine (non-specific agonist), atropine
      (non-specific antagonist), pirenzepine (M1 receptor antagonist), AF-DX116 (M2
      receptor antagonist) and 4-DAMP (M3 receptor antagonist) were administrated with
      intracerebroventricular injection (I.C.V. group) or intravenous injection (i.v.
      group). The drug effects on rhythmic bladder contraction were investigated.
      RESULTS: In I.C.V. group, the bladder contraction pressure were reduced by
      atropine, pirenzepine and 4-DAMP. The contraction time were shortened by
      pirenzepine and 4-DAMP but extended by AF-DX116. The contraction frequency was
      decreased by AF-DX116. Whereas AF-DX116 in i.v. group reduced the contraction
      pressure but did not cause any changes of the contraction time and the frequency.
      Other agents in i.v. group had same tendency with those of I.C.V. group except
      for intensity. CONCLUSION: That is to say AF-DX116 in I.C.V. group facilitate
      both micuturition center and storage center. In other words, these data indicate
      M2 receptor in rat brain inhibits both micurition and storage center. In
      addition, the effect of AF-DX116 in brain suggests that the development of new
      drug which proceed to central neuron system might provide a new treatment of
      neurogenic bladder.

PMID- 11968798
TI  - [The effect of high concentration of sodium and potassium ion on motility of
      human sperm preserved in electrolyte-free solution].
AB  - PURPOSE: To assess the effect of high concentration of sodium and potassium ion
      on the motilities of human sperm following the preservation in electrolyte-free
      solution. PATIENT: Semen samples were obtained from patients attending our
      infertility clinic. The motilities of their sperm were more than 40%. METHOD:
      Ejaculated sperm were washed by using the electrolyte-free Percoll gradient and
      then preserved in electrolyte-free solution at 4 degrees C for a week. The
      preserved sperm was incubated and analyzed after the addition of electrolyte
      solutions under acid or alkaline condition. The sperm were continuously preserved
      for a day at room temperature and analyzed. RESULT: The sperm was by the addition
      of 35-135 mM Na+ or 5-135 mM K+ in acid solutions. Under the alkaline conditions,
      sperm were reactivated without Na+ or K+. However, the addition of 135 mM Na+ or
      K+ significantly decreased in sperm motilities. The some sperm in the solution
      containing low concentration of Na+ or K+ ions maintained their motilities for a
      day at room temperature. However, all sperm lost their motilities in the 135 mM
      Na+ or K+ solutions. CONCLUSION: The high concentration of Na+ or K+ ions had
      detrimental effects on motilities of sperm following the preservation in
      electrolyte-free solution.

PMID- 11968799
TI  - [Risk factors for duration of urinary incontinence after radical prostatectomy].
AB  - PURPOSE: In this study, we examined risk factors for duration of incontinence
      after radical prostatectomy at our hospital. MATERIALS AND METHODS: From April
      1988 to March 2000, 45 patients with prostate cancer underwent retropubic radical
      prostatectomy at our hospital. Thirty-eight of 45 patients could be followed up.
      The patients' age, height, weight, body mass index (BMI), preoperative prostatic
      specific antigen level, clinical stage, nerve-sparing surgery or none, operation
      time, bleeding volume, resected prostate weight, cancer positive or negative at
      surgical margins, postoperative stage, radiation therapy or none, anti-androgen
      therapy or none, duration of postoperative incontinence, and follow-up period
      were examined. RESULTS: All patients had postoperative stress incontinence, and
      no one had urge incontinence. Medians of duration of postoperative incontinence
      and follow-up period were 5.5 and 12 months, respectively. When the patients were
      divided into 2 groups by the value of each parameter, postoperative anti-androgen
      therapy (chi 2 test, p = 0.0429) and high BMI (> or = 25.0 kg/m2, p = 0.0206)
      were related to the long duration (> or = 5.5 months) of postoperative
      incontinence. CONCLUSION: These results suggest that common factors are involved
      in the etiology of prolonged incontinence after radical prostatectomy and genuine
      stress incontinence in women. Therefore, both body weight control and pelvic
      floor muscle exercise might be also important for the treatment of incontinence
      after radical prostatectomy.

PMID- 11968800
TI  - [The clinical evaluation of 414 cases of male urethritis].
AB  - PURPOSE: We reviewed the clinical data of male urethritis diagnosed as sexually
      transmitted disease with the aim of revealing its clinical features. PATIENTS AND
      METHODS: In a total number of 414 males diagnosed as having acute urethritis
      transmitted by sexual activities between January and December in 2000, clinical
      data were collected and analyzed. In addition, questionnaire concerning the
      awareness of pharyngeal infection was obtained. RESULTS: Their ages ranged from
      16 to 60 years with a mean of 31 years. The source of infection was a commercial
      sexual worker (CSW) in 288 (69.6%) out of 414 cases. In 241 cases in whom an
      infection route was determined, 199 cases (82.6%) were considered to have an
      infection through oral sex. Microbiological examinations isolated Neisseria
      gonorrhea alone in 206 (49.8%), Chlamydia tracomatis alone in 47 (11.3%) and both
      in 46 (11.1%) cases. In our study, 57.5% and 20.8% of Neisseria gonorrhea strains
      were resistant to penicillin and new quinolones, respectively. Based on
      questionnaire, 174 (57.8%) out of 301 cases were not aware of possible infection
      from the pharynx through oral sex. CONCLUSION: The remarkable prevalence of
      gonococcal urethritis might be in part due to the lacking of awareness of
      infection through oral sex and sexual activities without a condom. Instruction on
      the prevention as well as the actual situation of urethritis is needed for
      general population with a broad age spectrum. The appropriate use of
      antimicrobial agents with sufficient susceptibility and less inductivity of drug
      resistance is also of clinical importance.

PMID- 11968801
TI  - [Analysis of immune response to tumor specific antigen restricted to HLA class II
      on renal cell carcinoma and its recognition mechanism].
AB  - PURPOSE: In this study, we studied the immune response against to human renal
      cell carcinoma and its antigensity. METHODS: Mixed lymphocyte tumor culture test
      was performed using tumor cells as stimulator cells, peripheral blood lymphocytes
      from tumor patient (autologous) or healthy volunteer (allogeneic) as responder
      cells, and tumor cells or peripheral blood lymphocytes from tumor patient as
      target cells. The cytotoxic activity of mixed lymphocyte tumor culture test was
      assayed by 51Cr-relase test, and cell surface antigens presented on tumor cells
      or peripheral blood lymphocytes were assayed by antibody block test. RESULTS: The
      cytotoxic activity against to tumor cells was induced from allogeneic peripheral
      blood lymphocytes by mixed lymphocyte tumor culture test. Its cytotoxic activity
      was inhibited by anti-CD8 antibody treatment of peripheral blood lymphocytes and
      anti-HLA class II antibody treatment of tumor cells. Furthermore, allogeneic
      peripheral blood lymphocytes induced to tumor cells did not damage peripheral
      blood lymphocyte of the tumor patient derivation. CONCLUSION: Renal cell
      carcinoma may express tumor specific antigen restricted to HLA class II antigens
      that could be recognized by allogeneic CD8 positive T lymphocytes.

PMID- 11968802
TI  - [Impact of a clinical pathway in cases of transurethral resection of the
      prostate].
AB  - OBJECTIVE: Because of recent increases in health care costs, cost containment has
      become a important issue in medical practice. We evaluated the effect on cost and
      clinical outcome with the implementation of clinical care pathway for
      transurethral resection of the prostate (TURP) patients. MATERIALS & METHODS: Our
      series consists of 69 consecutive patients treated with TURP between June 1, 1999
      and March 31, 2000. The patients were divided into two groups at random. Thirty
      two patients were treated on the clinical pathway (pathway group) and 37 patients
      were not placed on the clinical pathway program (non-pathway group). Total
      hospital charges, average length of stay and clinical outcomes were compared in
      two groups. RESULTS: The average of total hospital charges (insurance points) and
      average length of stay were 48,424.2 point, and 12.7 days for the pathway group,
      and 55.365.5 point, and 14.7 days for non-pathway group respectively.
      Postoperative complications and rehospitalization did not differ between two
      groups. DISCUSSION: With the implementation of the clinical care pathway, average
      hospital charges and length of stay were reduced. The clinical pathway program is
      considered to be a good tool for health care cost management. This methodology
      can be applied to all patients. However, when we make the clinical pathway
      program, we take into account the individuality of each patients.

PMID- 11968803
TI  - [Adjuvant hormone therapy in patients with positive surgical margins after
      radical prostatectomy].
AB  - BACKGROUND: We carried out a retrospective study comparing radical prostatectomy
      plus adjuvant hormone therapy with radical prostatectomy plus surveillance in
      patients with positive surgical margins to evaluate whether adjuvant hormone
      therapy is beneficial for disease free survival. PATIENTS AND METHODS: Sixty-five
      patients with positive surgical margins after radical prostatectomy were included
      in this study. Twenty-six patients received adjuvant hormone therapy. Thirty-nine
      patients underwent surveillance with salvage hormone therapy at PSA failure. None
      of these 65 received androgen deprivation prior to surgery. Treatment outcomes
      were measured in terms of progression free survival. RESULTS: Five year clinical
      progression free survival rates for the patients with positive surgical margins
      in the adjuvant therapy group and surveillance group were 85.9% and 80.0%
      respectively (p = 0.85). Clinical progression free survival between the groups
      was not statistically different in terms of seminal vesicle involvement and tumor
      grade. The difference of clinical progression free survival between the two
      groups approached statistical significance in poorly differentiated tumor (p =
      0.08). CONCLUSIONS: We conclude that adjuvant hormone therapy is not beneficial
      in terms of progression free survival in patients with positive surgical margins.
      Nevertheless, adjuvant hormone therapy could be beneficial in patients with
      poorly differentiated prostate cancer.

PMID- 11968804
TI  - [Treatment of 2019 cases with upper urinary tract calculi using a piezoelectric
      lithotriptor ESL-500A].
AB  - PURPOSE: We evaluated the results of extracorporeal shock wave lithotripsy (ESWL)
      in a large number of cases with upper urinary tract calculi, and reported the
      strategy how to improve the efficacy and safety of ESWL. PATIENTS AND METHOD:
      Eight hundred fifteen patients with renal calculi and 1,204 patients with
      ureteral calculi were treated using a piezoelectric ultrasound-guided
      lithotriptor, Toshiba ESL-500A. Auxiliary measures were needed in 51 cases (2.5%)
      and 1,968 cases (97.5%) were treated by in situ procedures. ESWL was performed
      with the optimal positioning of the patient and under the continuous monitoring
      by ultrasound system. The visibility of stones was improved by removal of
      abdominal gas and administration of diuretic agent to dilate the ureter. Cases
      with urinary tract infection were medicated by antibiotics and the obstruction of
      the urinary tract was cleared away as soon as possible. RESULTS: Including the
      cases with residual fragments less than 4 mm, the success rates at one month
      after the treatment were 97.7% and 98.7% for the renal and ureteral calculi,
      respectively. The mean numbers of sessions were 1.49 for renal calculi and 1.16
      for ureteral calculi. Multiple sessions were required in 24.2% of renal calculi
      and 12.0% of ureteral calculi. No serious complication has been observed except
      for three cases, which were sepsis after ESWL, anuria in a solitary kidney, and
      pyonephrosis caused by Steinstrasse with urinary infection, respectively.
      CONCLUSION: ESWL using ESL-500A is an efficient treatment of upper urinary tract
      calculi which has higher pulverization rate and fewer complications in the
      adequate procedure.

PMID- 11968805
TI  - [Carcinoma in situ of the penis rapidly progressing after carbon dioxide laser
      treatment].
AB  - Laser treatment is considered to be effective in treating carcinoma in situ of
      the penis. We, however, report a case with carcinoma in situ of the penis which
      developed invasive carcinoma and inguinal lymphnode metastases only 6 months
      after the laser treatment. A 74-year-old man with pseudophimosis presented with
      redness of the glans penis. A physical examination revealed thick erythema, 12
      millimeters in diameter, around the external urethral meatus. Histologically,
      biopsy revealed squamous cell carcinoma in situ. No metastasis was suspected by
      physical examination and imaging studies. Although the lesion appeared to
      slightly extend into the urethra, it was primarily treated with the CO2 laser.
      Six months after the treatment, however, local recurrence was confirmed by the
      touch smear cytology, resulting in the partial amputation of the penis. The
      histopathological examination revealed subepithelial and marked lymphatic
      invasion of the tumor and positive margin in the urethral stump (squamous cell
      carcinoma in situ). Further, since bilateral superficial inguinal lymphnode
      swelling appeared, total amputation of the penis with perineal urethrotomy and
      pelvic/inguinal lymphnode dissection was performed subsequently. The metastases
      to bilateral inguinal lymphnodes were confirmed histologically. The patient
      received adjuvant chemotherapy and has been alive and well without evidence of
      disease 40 months after the initial treatment.

PMID- 11968806
TI  - [Tunica vaginalis testis autografting for Peyronie's disease: report of two
      cases].
AB  - Two patients with refractory Peyronie's disease were treated by tunica vaginalis
      testis autografting following surgical excision of indurated tunica albuginea of
      the corpora cavernosa. One patient could achieve relief of pain and a straight
      erection of the penis 3 months after surgery. Another patient could not obtain a
      satisfactory erection during the follow-up of 6 months, but could have sexual
      intercourse after 7 months. A tunica vaginalis testis autograft might be an ideal
      substitute for tunica albuginea because it has several advantages: it causes no
      rejection at the recipient site; it is flexible enough to accommodate to
      expansion; there is no development of sebaceous glands and hair follicles that
      may occur in the use of a dermal graft; and it is easy to obtain.

PMID- 11968807
TI  - [Perinephric liposarcoma mimicking cystic renal tumor].
AB  - Liposarcoma is one of the most common primary retroperitoneal neoplasms, and the
      perinephric region is a frequent location for them. Liposarcomas show a variety
      of radiographic features in terms of histological types and tumor sizes, so the
      specific diagnosis of liposarcoma is often difficult. We present a unique case of
      perinephric dedifferentiated liposarcoma mimicking cystic renal tumor. A 71-year
      old man presented himself at our hospital with a palpable mass in his upper right
      abdomen. Abdominal computerized tomography (CT) revealed a well-defined cystic
      mass at the lower pole of the right kidney that contained heterogeneous solid
      components and small foci of fat. There were no signs of lymphadenopathy or tumor
      thrombus in the renal vein. Metastatic evaluation by chest x-ray and bone scan
      was negative. The probable diagnosis was cystic renal cell carcinoma or atypical
      angiomyolipoma. Because we could not exclude the possibility of cystic
      malignancy, a right radical nephrectomy was performed. Grossly, the tumor was
      predominantly encapsulated by a unilocular fibrous capsule and was filled with
      bloody fluid and debris. The anterior portion of the tumor was composed of
      various-sized soft and rubbery masses covered with necrotic tissue. The
      histological diagnosis was dedifferentiated liposarcoma arising in the
      perinephric retroperitoneum with extensive necrosis, and the cyst wall was
      composed of a necrotic tumor with a well differentiated liposarcoma and a fibrous
      capsule. Although the tumor widely covered the right kidney, there was no
      microscopic invasion of the kidney. No signs of tumor recurrence were noted six
      months after the operation.

PMID- 11968808
TI  - [Nephrogenic adenoma of the bladder in children].
AB  - We report an unusual case of a 3-year-old girl with multiple nephrogenic adenomas
      in the urinary bladder following previous surgical intervention. When she was 6
      month-old, right vesicoureter-alreflux (VUR) and left marked hydronephrosis with
      ectopic urethral opening were found. The left renal pelvis and ureter were
      incompletely duplicated with a short common segment. Bilateral
      ureterocystoneostomy and closure of ectopic opening of the left ureter were
      performed. Left ureteral orifice resulted in double barreled pattern.
      Postoperative voiding-cystourethrography revealed VUR in the ureter belonging to
      the lower part of the left kidney. At the age of 3 year, cystoscopic examination
      revealed multiple papillary lesions in the urinary bladder. These lesions were
      resected transurethrally and the pathologic diagnosis was nephrogenic adenoma.
      The patient is the 27th case of nephrogenic adenoma of bladder reported in the
      Japanese literature.

PMID- 11968810
TI  - [Diagnosis and surgical treatment for the intra-extracranial dissecting
      aneurysm].

PMID- 11968809
TI  - [A case of adrenocortical carcinoma with masculinization, obtaining long
      prognosis with surgical treatment alone].
AB  - A 28 year-old woman presented right upper abdominal pain. She had been pointed
      out her masculinization and amenorrhea. CT scan and magnetic resonance imaging
      showed right adrenal tumor. In the endocrinological study, the serum cortisol and
      testosterone was elevated. Transabdominal right adrenalectomy and nephrectomy was
      carried out and histopathological diagnosis was adrenocortical carcinoma. The
      masculine symptom had disappeared after the operation and she has been without
      recurrence for five years.

PMID- 11968811
TI  - [Clinical features and current status of diagnosis and management of
      vertebrobasilar artery dissections in Japan].

PMID- 11968813
TI  - [Clinical symptoms and speech disturbance in frontotemporal dementia and
      parkinsonism linked to chromosome 17 with tau mutation].

PMID- 11968812
TI  - [Gene therapy for cerebral infarction (cerebral ischemia)].
AB  - The treatment strategies of cerebral infarction have been studied in order to
      prevent neuronal cell death. Gene therapy is one of the most promising therapy
      and has several advantage over classical drug therapies. There has been a problem
      that drug proteins are unable or difficult to pass through blood brain barrier.
      In gene therapy, however, drug proteins are expressed in the brain with transgene
      transfer technique. Ischemic neural death proceeds with a complex series of
      pathophysiological events in the neurons. But molecular mechanism of ischemic
      neuronal cell death gradually understood. It has been known that a number of
      genes can be potent candidates for treatment factors of cerebral infarction.
      Actually, many investigators have been studied treatment strategies of cerebral
      infarction using a variety of neurotrophic factors such as bcl-2, heat shock
      protein 72, glial cell line-derived neurotrophic factor (GDNF), and hepatocyte
      growth factor (HGF). Moreover, the development of new vectors and gene delivery
      systems have been studied. Gene therapy would be a strong strategy for treatment
      of cerebral infarction in the future.

PMID- 11968814
TI  - [A clinical study of pachymeningitis].
AB  - We report five patients with cranial and spinal pachymeningitis not associated
      infections or tumors. The underlying causes of pachymeningitis in four patients
      were Sjogren syndrome, Wegener's granulomatosis, microscopic polyangitis, and
      dermatomyositis, respectively. In one patient, the cause was unknown.
      Cerebrospinal fluid analysis showed an increase in cells in only one patient and
      elevated protein levels in three patients. Blood test revealed an inflammatory
      disease except in one patient. The anti-nuclear antibody was present in four of
      five patients examined, and P-ANCA was present in two out of four patients. The
      prognosis was good except in one patient of Wegener's granulomatosis. We reviewed
      48 previously reported cases of pachymeningitis were not associated infections or
      tumors. The lesions of pachymeningitis were more localized in the cranial dura
      than the spinal dura, and many cases had immunological abnormalities.

PMID- 11968815
TI  - [Magnetoencephalographic and electroencephalographic source localization of the
      interictal spike activities in patients with medial temporal lobe epilepsy].
AB  - Magnetoencephalographic (MEG) and electroencephalographic (EEG) source
      localization of the interictal spike activities was performed in 5 patients with
      medial temporal lobe epilepsy (MTLE) to clarify the usefulness of MEG as the
      preoperative noninvasive examination. According to the Ebersole's classification
      based on the pattern of spike source localization and orientation, three patients
      were classified to posterior temporal vertical type, one anterior temporal
      horizontal type, and one anterior temporal vertical type. In all cases, the MEG
      and EEG spike did not completely coincide in waveform with each other. The
      latency of the best correlated equivalent current dipole (ECD) with MEG was
      slightly shorter than the peak latency of EEG spike. Although the EEG-source
      montage images at this latency were failed to reveal the potential to be
      localized to the medial temporal lobe, they demonstrated the potential to extend
      to the lateral temporal lobe at the peak latency of EEG spike. All patients
      became seizure free following anterior temporal lobectomy with hippocampectomy.
      The MEG spike source localization based on the Ebersole's classification may be
      calculated by the potential extended to the lateral temporal lobe, and, thus, was
      not useful in the diagnosis of MTLE and for predicting postoperative seizure
      outcome.

PMID- 11968816
TI  - [Early ischemic lesion demonstrated by ictal diffusion-weighted MRI during prior
      TIA in a patient with cerebral infarction].
AB  - We reported a patient with transient ischemic attack (TIA), subsequently evolving
      to a cerebral infarction, in whom ictal diffusion-weighted magnetic resonance
      imaging (MRI) detected early ischemic lesion in the left hemisphere. The patient
      was a 30-year-old right-handed male medical doctor, who had an in-hospital
      episode of TIA with obtundation and right hemiparesis, which lasted for 150
      minutes. Ictal diffusion-weighted MRI obtained 110 minutes after symptom onset
      demonstrated an area of high signal intensity in the left striatum and corona
      radiata, whereas T 2-weighted and FLAIR images were entirely normal. Ictal
      magnetic resonance angiography (MRA) showed occlusive lesions in the M 2 branches
      of the left middle cerebral artery. The second MRA obtained 90 minutes after
      resolution of the symptoms showed nearly complete recanalization of the left
      middle cerebral artery, suggesting that the TIA was embolic mechanism. However
      the patient rapidly developed similar neurological symptoms again 58.5 hours
      after the TIA episode, evolving finally to a completed stroke. A brain CT
      obtained 1 hour after the second episode demonstrated diffuse hypodense lesions
      in the left basal ganglia and corona radiata, and in the left temporal lobe. MRIs
      3 and 7 days later displayed completed infarcts, of which distribution was
      consistent with that of the hypodense lesions on the earlier CT. The left middle
      cerebral artery remained patent on the follow-up MRAs. The patient fairly
      recovered and returned to his premorbid position as medical doctor with a mild
      residual right hand clumsiness. In this patient, ictal and post-ictal MRAs
      documented an occlusion and a reopening of the middle cerebral artery. The
      embolic mechanism remains unknown despite detailed cardiac, vascular, and
      hematological examinations. In addition to recurrent embolism, we would like to
      point out that the reperfusion injury, secondary delayed neuronal death, and
      other factors may be involved in the second exacerbation evolving to the
      completed stroke.

PMID- 11968817
TI  - [A case of falcotentorial meningioma with visual allesthesia].
AB  - Visual allesthesia, in which visual images are transposed from one homonymous
      half-field of visual field to another, is a rare phenomenon. Palinopsia is the
      persistence or recurrence of visual images after the exciting stimulus object has
      been removed. Some authors have reported these phenomena, but these
      pathophysiology has not been understood. We report a right-handed 63-year-old
      woman, with a right falcotentorial meningioma. She paroxysmally experienced
      illusory transpositions of objects viewed in the right homonymous visual field
      into the left, and she recognized her face in it. The illusory images were
      palinoptic, persisting for up to a few minutes after the real objects were no
      longer in view. Administration of anticonvulsant medications resulted in the
      decrease of frequency of this phenomenon. Radiological and surgical findings
      revealed that the tumor was compressing the very localized visual cortex,
      especially the Brodmann's area 18 and 19. After resection of the tumor, visual
      allesthesia and palinopsia completely disappeared. These areas are associated
      with memory and recognition of visual images as visuopsychic area. This case
      provides some insight into the mechanisms of this phenomenon, and we consider
      that it could be caused by seizure activity in this lesion.

PMID- 11968818
TI  - [Ischemic enlargement of the brainstem in a patient with megadolichobasilar
      artery].

PMID- 11968819
TI  - [A case of influenza-associated encephalopathy or encephalitis diagnosed by
      diffusion-weighted magnetic resonance imaging].

PMID- 11968820
TI  - [Multiple system atrophy which had been treated as juvenile Parkinson's disease].

PMID- 11968821
TI  - [Neurosurgery in the 21st century--development of stereotactic and functional
      neurosurgery].

PMID- 11968822
TI  - [Neurosurgery in the 21st century--cerebrovascular disease].

PMID- 11968823
TI  - [Stereotactic surgery for treatment of Parkinson's disease].

PMID- 11968824
TI  - [Usefulness of dynamic digitized cerebral parenchymography for cerebral vascular
      disease].
AB  - Aortic arch injections according to Theron's method have been performed in
      patients with cerebral ischemia. Digital subtraction angiograms with modified
      windowing (low and narrow) have been used for better visualization of cerebral
      parenchymal condition. This "cerebral parenchymography" allows much easier
      understanding of cerebral parenchymal vascularization on angiographic imaging.
      Although further study is necessary to estimate accurate cerebral blood flow,
      this technique can enable an easy and quick understanding of the overall cerebral
      hemodynamics.

PMID- 11968825
TI  - [Presurgical functional mapping of the sensorimotor area using evoked magnetic
      fields].
AB  - In the present study, we evaluated the usefulness of magnetoencephalography (MEG)
      for presurgical identification of not only the central sulcus by somatosensory
      evoked magnetic fields (SEFs), which is a well-known, reliable technique, but
      also the primary hand motor area by movement-related cerebral magnetic fields
      (MRCFs). Subjects were 10 patients with brain tumor (6 glial tumors, 3 cavernous
      angiomas, and 1 metastatic tumor) around the sensorimotor area. Identification of
      the central sulcus by SEF responses to multiple sites of stimulation (median
      nerve, tibial nerve, thumb, and lower lip) was performed in all patients, and
      identification of the hand motor area by MRCF responses to the index finger
      extension task was made in 9. All MEG data were superimposed on sectional or
      three-dimensional magnetic resonance (MR) images. The central sulcus was clerAly
      identified by SEFs in all patients, even in 5 whose MR images showed severe
      distortion, and the primary hand motor area was identified by MRCFs in 6 of 9
      patients. The central sulcus and primary motor area identified by MEG were
      confirmed by cortical recording of somatosensory evoked potentials in response to
      median nerve stimulation in 7 patients and motor evoked potentials in response to
      direct cortical stimulation in 5. All patients underwent tumor removal guided by
      functional mapping by MEG and experienced no surgical complications. In
      conclusion, MEG is a useful tool in presurgical functional mapping of the
      sensorimotor area. This is the first report of a case in which identification of
      the hand motor area by MRCFs was used in a clinical setting.

PMID- 11968826
TI  - [The relationship between the severity of a neurological condition and the blood
      coagulation/fibrinolytic system in patients with spontaneous subarachnoid
      hemorrhage].
AB  - In order to examine the relationship between the hemostatic systems and the
      severity of neurological changes, shortly after spontaneous subarachnoid
      hemorrhage (SAH) we reviewed 30 patients who had been admitted within 6 hours
      after the onset of SAH. Peripheral blood samples were obtained within 6 hours of
      the onset of SAH. There was a significant correlation between increased values of
      serum antithrombin III, thrombin-antithrombin III complexes, fibrinopeptide B
      beta 15-42, D-dimers, and the neurological severity of SAH. The data suggest that
      the activation of the blood coagulation system as well as the fibrinolytic system
      (especially the secondary fibrinolysis) occurs early in the course of SAH,
      particularly in patients with a severe neurological condition.

PMID- 11968828
TI  - [A case of a ruptured anterior communicating aneurysm which was originally the
      smallest of several unruptured aneurysms].
AB  - A 64-year-old male suddenly developed headache and nausea. He had been pointed 3
      years before out as having an unruptured basilar artery aneurysm and a right
      middle cerebral artery aneurysm. Computed tomography (CT) revealed diffuse
      subarachnoid hemorrhage in the basal cistern and bilateral Sylvian and
      interhemispheric fissures. Hematomas in the anterior horns of the lateral
      ventricles and third ventricle were also seen. Angiography revealed an anterior
      communicating artery aneurysm, which, retrospectively, had been recognized as a
      small dilatation of artery wall 3 years before. An operation was performed and
      the anterior communicating artery aneurysm was successfully clipped. The
      intraoperative findings revealed the aneurysm was the ruptured one. The risk of
      rupture and surgical indication for unruptured small aneurysms are discussed.

PMID- 11968827
TI  - [Extracorporeal ventriculoatrial shunt with the use of one-way ball valve].
AB  - We developed a simple system of an "extracorporeal" ventriculoatrial (VA) shunt
      using a one-way ball valve (Acty valve II, Kaneka Medix) to release the patient
      from postoperative constraint during the ventricular drainage. The system is
      constructed in such a way that the ventricular drainage tube is connected to the
      central venous catheter via a one-way valve. The CSF is regulated by using the
      valve and is diverted into the systemic circulation as in the conventional
      ventriculoatrial shunt. After 2 or 3 weeks of CSF diversion through the
      extracorporeal VA shunt, a ventriculoperitoneal shunt is placed if hydrocephalus
      is apparent by temporary occlusion of the system. We applied this system to 4
      patients with hydrocephalus, and we found it useful and free from adverse
      effects. The patient was freed from physical constraint involved in conventional
      ventricular drainage and an effective program of early rehabilitation was able to
      be started.

PMID- 11968829
TI  - [Magnetoencephalographic localization of multiple seizure foci for surgical
      treatment of intractable frontal lobe epilepsy: confirmation with intra-operative
      electrocorticography].
AB  - A successfully treated case of intractable FLE, of which preoperative
      magnetoencephalography (MEG) provided multiple spike localization and
      intraoperative corticogram (ECoG) confirmed the resection area. A 22-year-old
      male patient, with a history of subdural abscess at the age of 14 years, had
      suffered frequent simple (SPSs) and complex partial seizures (CPSs) and falling
      attacks since the age of 16 years. Although he underwent corpus callosotomy at
      the age of 17 years, additional surgical treatment was considered because of
      intractable and more frequent SPSs and CPSs. Magnetic resonance (MR) imaging
      demonstrated diffuse lesions in the right frontal lobe. Although, both interictal
      and ictal electroencephalography (EEG) failed to show focal epileptogenic
      localization, interictal MEG localized several clusters over the multiple
      anatomical lesions in the right prefrontal and frontal opercular regions. The
      patient underwent right fronto-temporal craniotomy, and anterior frontal
      lobectomy, followed by lesionectomy of the premotor area based on the
      intraoperative ECoG findings. The ECoG localized frequent spike discharges over
      the right prefrontal, frontal operculum and premotor cortices, which showed good
      correspondence with the MEG findings. MEG can be a useful noninvasive method for
      presurgical evaluation of intractable FLE.

PMID- 11968830
TI  - [A dissecting aneurysm of the posterior inferior cerebellar artery was reduced
      spontaneously during conservative therapy: case report].
AB  - We report here a case of a patient with a dissecting aneurysm of the anterior
      medullary segment of the posterior inferior cerebellar artery (PICA) which
      presented with Wallenberg's syndrome. A 32-year-male presented with an unusual
      case of Wallenberg's syndrome due to a dissecting aneurysm of the PICA
      manifesting as a sensation of heaviness in the occipital region and vertigo. The
      occipital symptoms persisted and vertigo and vomiting developed after 6 days.
      Numbness developed on the left side of the patient's face, and hyperalgesia on
      the right side of the body. The diagnosis of Wallenberg's syndrome was based on
      the above findings. MRI revealed infarction of the lateral aspect of the medulla
      oblongata and MR angiography revealed dilatation in the proximal portion of the
      left PICA. Digital subtraction angiography revealed that the left vertebral
      artery was essentially normal, but there was a spindle-shaped dilatation in the
      proximal portion of the left PICA. We carried out conservative therapy at the
      patient's request and 3D-CTA revealed that the dissecting aneurysm was markedly
      reduced in size seven months after the onset. Dissecting aneurysms of the
      intracranial posterior circulation have been shown to be less uncommon than
      previously thought. However, those involving the PICA without involvement of the
      vertebral artery at all are extremely rare. The natural history of the dissecting
      PICA aneurysm was unknown, and the indication for surgical treatment of such
      aneurysms remains controversial. Management options are conservative treatment,
      open surgical treatment including wrapping, trapping, and resection with
      reconstruction, but almost all of the patients underwent radical treatment to
      prevent rupture of the aneurysm. However we had no knowledge of the risk of
      rupture of a PICA dissecting aneurysm presenting with ischemic symptoms. We have
      reviewed the well-documented 15 cases of dissecting aneurysms of the PICA
      reported in the literature and we discuss the management of the dissecting PICA
      aneurysm presenting with ischemic symptoms.

PMID- 11968831
TI  - [Recurrent cerebellar abscess secondary to middle ear cholesteatoma: case
      report].
AB  - We report a case of recurrent cerebellar abscess secondary to middle ear
      cholesteatoma. A 57-year-old man was admitted to our hospital because of symptoms
      of headache and nausea in August, 1992. Brain CT scans revealed acute
      hydrocephalus complicated by a cerebellar abscess. The patient was discharged
      without any neurological deterioration after systemic antibiotics combined with
      intrathecal aminoglucoside administration via ventricular drainage. Mannitol was
      also administrated for 7 days immediately after the patient's admission. The
      clinical course was uneventful for 8 years afterwards. Follow-up MR images
      revealed no signs of recurrence. Unfortunately, the patient suffered a recurrence
      of cerebellar abscess in October, 2000. His condition continued to deteriorate in
      spite of being treated by systemic antibiototics. MR images and CT scans
      targeting a portion of his middle ear revealed extensive pus-coated mastoiditis
      and middle ear cholesteatoma. We thus performed radical mastoidectomy including
      removal of the middle ear cholesteatoma. After the operation, the cerebellar
      abscess was ameliorated. He has been free from recurrence for 2 years, so far.
      Early diagnosis and prompt intervention are necessary for reducing mortality and
      morbidity rates due to otogenic brain abscess. Recognizing middle ear
      cholesteatoma as one of the major causes of neurological entities in the
      cerebellopontine angle portion, accurate otological examination and prompt
      treatment can possibly bring about a better prognosis.

PMID- 11968832
TI  - [Combination of stenting and coil embolization for carotid artery pseudoaneurysm
      causing symptomatic mass effect: case report].
AB  - A case of cervical pseudoaneurysm secondary to carotid artery dissection causing
      symptomatic mass effect was reported. A 60-year-old woman presented with the
      complaint of right neck swelling and dysphagia that was considered to be the mass
      effect of a pseudoaneurysm caused by dissection of the right common carotid
      artery (CCA). Although a self-expanding stent was deployed to cover the orifice
      of the pseudoaneurysm, the pseudoaneurysm had been enlarged because of thrombus
      formation on the inner wall. A microcatheter was guided through the stent mesh
      into the aneurysm, and Guglielmi detachable coils were placed to embolize the
      orifice. One month later, angiography revealed complete embolization of the
      aneurysm while preserving flow in the CCA. The mass effect attributable to the
      pseudoaneurysm was relieved symptomatically as well as radiologically. Carotid
      artery dissection with symptomatic mass effect can be treated successfully, using
      a combination of stent and coils. This method may be considered to be an
      alternative to conventional surgical treatment such as proximal ligation,
      extracranial-intracranial bypass, or direct surgical repair.

PMID- 11968833
TI  - [Measurement of surface strains in crowns and 3-unit bridges during function].
AB  - The purpose of this study was to determine the surface strain distribution of a
      crown and bridge, and to compare the biomechanical behavior of a crown and
      bridge. The complete crown and 3-unit bridge, whose abutments were the second
      premolar and the second molar, for three cases of first molar deficit in the
      mandible, were produced, and the surface strain of prostheses under static
      loading was measured with strain gauges. When a load was applied, although only a
      small strain was observed near the margin of the crown, a comparatively large
      tensile strain was observed near the deficit side margin of the distal retainer
      on the bridge. In the case of a 3-unit bridge, since there is the possibility
      that strain will occur in the distal retainer, it is necessary to consider the
      design of the distal retainer during preparation.

PMID- 11968834
TI  - [Identification of periodontopathic bacteria DNA from periodontitis-involved
      gingival tissue using a PCR method].
AB  - The purpose of this study was to determine the presence of periodontopathic
      bacteria DNA in the granulation tissue of periodontally involved gingival tissue.
      Forty periodontitis patients were examined. Subgingival plaque and saliva samples
      were collected from the patients before surgery. Then, granulation tissue was
      also collected during surgery. Another 20 patients, who had more than 4 mm in
      probing pocket depth, were also examined as a control. They received only initial
      treatment without periodontal surgery. Plaque and saliva samples were also
      collected from them. Seven periodontopathic bacteria, Porphyromonas gingivalis,
      Bacteroides forsythus, Toreponema denticola, Campylobacter rectus, Actinobacillus
      actinomycetemcomitans, Prevotella intermedia, and Prevotella nigrescens, were
      detected by a PCR method from these samples of all patients. As clinical
      parameters, probing pocket depth, clinical attachment level, and bleeding on
      probing were recorded. One year after surgery, sampling of subgingival plaque and
      saliva, and measurement of clinical parameters were performed on the patients.
      The DNA of periodontopathic bacteria was detected in the granulation tissue of 29
      out of 40 patients. P. gingivalis, B. forsythus, T. denticola, C. rectus, A.
      actinomycetemcomitans, P. intermedia and P. nigrescens were detected in 23, 11,
      12, 9, 3, 2 and 1 subject(s) respectively. The sites with undetectable level of
      any periodontal pathogens at one year after surgery showed a clinical attachment
      gain of 2.44 mm, while those that showed detectable pathogen levels had only a
      0.77 mm gain. Our results indicated that the removal of granulation tissue
      contributed to eliminating periodontal pathogens and to avoiding re-infection by
      those bacteria. Complete eradication of periodontopathic bacteria would be
      necessary for successful periodontal treatment.

PMID- 11968835
TI  - [Clinical study of risk management for dental implant treatment--changes of blood
      pressure and pulse rate during implant surgery under local anesthesia].
AB  - The changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), and
      pulse rate (PR) during implant surgery under local anesthesia were analyzed in 38
      normal healthy patients. The results were as follows: 1. SBP significantly
      increased compared with the preoperative control throughout surgery. 2. DBP did
      not change significantly compared with the preoperative control throughout
      surgery. 3. PR increased just after the local anesthesia, and lowered afterward.
      4. Both SBP and DBP increased in correlation with age. 5. SBP, DBP, and PR
      increased in correlation with surgical procedure time. 6. SBP, DBP, and PR
      increased in correlation with number of implantation. From these results, it was
      indicated that implant surgery might be accompanied by a risk, even in healthy
      patients.

PMID- 11968836
TI  - [Application of a CO2 laser for oral soft tissue surgery in children in Sri Lanka
      -introduction of a laser through activities of aid to a developing country].
AB  - The objective of this study was to clarify the effect of CO2 laser irradiation on
      oral tissue problems in children in Sri Lanka, through the activities of aid to a
      developing country by the Japan International Cooperation Agency. This study took
      about six months, during two times periods: from November 2000 to February 2001,
      and from July 2001 to October 2001, in the paedodontic clinic of the Faculty of
      Dental Science, University of Peradeniya, in Sri Lanka. A CO2 laser was used on
      48 subjects (51 cases), aged between 1 and 15 years, having main indications for
      labial frenectomy, frenectomy in ankyloglossia, and excision of mucocele. The
      results indicated that the CO2 laser had the following advantages. 1. Soft tissue
      cutting was efficient, with no bleeding, giving a clear operative field during
      operation. 2. There was no need to use sutures. 3. The surgery itself was simple
      and less time-consuming. Hence, there was no need for general anesthesia for such
      cases as tongue tie operation in small children. 4. There was no postsurgical
      infection. As a result, there was no need for analgesics or antibiotics, as post
      surgical pain and infection were prevented. 5. Wound contraction and scarring
      were decreased or eliminated. Considering the above advantages, the use of a CO2
      laser proved to be very safe and effective for soft tissue surgery, especially
      for children in developing countries such as Sri Lanka.

PMID- 11968837
TI  - [Brain regions activated during the mandibular movement tasks in functional
      magnetic resonance imaging].
AB  - Brain regions activated during the mandibular movement were evaluated by fMRI.
      Eight healthy right-handed volunteers as examinees were included in this study.
      Echo planar imaging of fMRI were obtained with the gradient echo sequence using
      1.5 T MR scanner. All examinees were subjected to complete six tasks of
      mandibular movement; simple mouth opening and closing movement, protrusive
      movement, retrusive movement, right lateral movement, left lateral movement, and
      imaginary mouth opening and closing movement. The stimulation paradigm consisted
      of 7 cycles of scans. Each cycle consisted of 10 repeated imagings during "on"
      and "off" periods of each 5 seconds. The head of examinee in the supine position
      was fixed, to minimize involuntary motions during all functional measurements,
      before motions of the head were measured. The following conclusions were
      obtained. 1. The examinations were achieved with minimal artifacts caused by
      motions of the head. 2. The region of motor cortex activation by the mandibular
      movements approximately agreed with those reported by electrophysiological
      methods in animals, such as cats and monkeys. 3. Activated area of motor cortex
      and the supplementary motor area were further extended according to the move
      complex mandibular movements. 4. Possible involvement of the parietal association
      area was indicated in the lateral movements. 5. Activation of the motor speech
      area was observed during lateral mandibular movement. Possibility of the
      involvement of the Broca's area was indicated in mandibular movement. It was thus
      concluded that fMRI may be useful to analyze the brain regions activated by
      mandibular movement.

PMID- 11968838
TI  - [The role of rat cytokine-induced neutrophil chemoattractants (CINCs) in
      inflammation].
AB  - Rat cytokine-induced neutrophil chemoattractants (CINCs) are the members of the
      CXC chemokine family. Four neutrophil chemokines, CINC-1, CINC-2 alpha, CINC-2
      beta and CINC-3, were purified from the conditioned medium of granulation-tissue
      culture. CINC-2 alpha and CINC-2 beta differ only in the sequence of three
      carboxy-terminal residues and are produced by alternative splicing. CINC-3 had
      neutrophil chemotactic activity similar to that of CINC-1 and CINC-2, but induced
      greater calcium mobilization than CINC-1 and CINC-2. CINC-1, -2 and -3 induced
      calcium flux in CXCR2-transfected HEK293 cells. In addition, anti-CXCR2 serum
      inhibited neutrophil chemotactic activities of the three types of CINCs almost
      completely. These results indicate that rat CXCR2 is a unique receptor for CINC
      1, -2 and -3. CINCs induced calcium mobilization through pertussis toxin
      insensitive G-protein but induced chemotaxis through pertussis toxin-sensitive G
      protein. CINC-1/-2 and CINC-3 may stimulate both G-proteins with distinct
      efficiency. The concentration of CINC-1 increased transiently in rat air
      pouch/lipopolysaccharide inflammation, whereas the CINC-2 level increased
      linearly. The number of infiltrated cells increased up to 8 h. The increase in
      cell number was correlated with the total concentration of CINC-1 and CINC-2.
      Northern blot analyses and enzyme-linked immunosorbent assay showed that CINC
      expression was very low in rat macrophages without stimulation and increased
      after lipopolysaccharide stimulation. These data suggest that CINCs are expressed
      by inflammatory cells such as macrophages at a site of inflammation and play
      important roles in neutrophil infiltration.

PMID- 11968839
TI  - Clinical estimation of vancomycin measurement method on hemodialysis patient.
AB  - The fluorescence polarization immunoassay (FPIA) method is used to perform
      measurement of vancomycin hydrochloride (VCM) at many institutions. However, the
      values measured by the FPIA method are more vulnerable to overestimation than the
      high performance liquid chromatography (HPLC) method. In particular, it was not
      reported to perform exact therapeutic drug monitoring (TDM) measurement. Since
      overestimation is likely in patients with renal dysfunction, the HPLC method is
      preferable for TDM measurement. This study investigates the clinical conditions
      that lead to overestimation in the FPIA method, paying attention to the relation
      of clinical laboratory data inspection values and the existence of hemodialysis
      (HD). Overestimation in the evaluation of TDM using the FPIA method was
      clinically examined with 116 serum samples obtained from 18 cases medicated with
      VCM. The relevance between overestimation of patients who had not had HD
      performed was 72.7 +/- 61.7% (means +/- SD). In short, the overestimation was
      greatest in HD patients. Since overestimation did not affect the evaluation of
      clinical TDM, such as an effect and a side-effect, the TDM of VCM was shown to be
      satisfactorily evaluated by the simple FPIA method.

PMID- 11968840
TI  - [Noninvasive detection of dynamics of various elements in the upper abdomen of
      selenium-deficient rat using multitracer analysis technique].
AB  - The advantages of a technique as a diagnostic tool for examining the distribution
      of bio-trace elements in the living body are discussed. Time courses of the
      distribution of Be, V, Mn, Fe, Co, Zn, As, Se, Rb, Sr, and Y in the upper abdomen
      of living selenium-deficient rats were examined using the in vivo multitracer
      analysis technique. The dynamics of the elements were estimated by comparison
      with the distribution of As. Almost all As was taken up by red blood cells. The
      present findings of a decrease in Se and increase in Co in the liver of Se
      deficient rats are in good agreement with the previous data that showed a
      decrease in Se and increase in Co uptake into the liver cell fraction of Se
      deficient rats. Although the normalized uptake rate and the relative distribution
      of Co 48 h after administration increased in Se-deficient rats, the early level
      of the relative distribution of Co was not lower compared with that in the normal
      group. This suggests that the high level of the normalized uptake rate and the
      relative distribution of Co in Se-deficient rats were affected by the decreasing
      excretion rate rather than by the increasing uptake rate of Co. The plateau level
      of relative distribution of Se in the Se-deficient rats is lower than that in
      normal rats, suggesting that the lower levels of the normalized uptake rate and
      relative distribution of Se in Se-deficient rats were due to the decreased uptake
      rate of the element.

PMID- 11968842
TI  - [Antibacterial constituents against Helicobacter pylori of Brazilian medicinal
      plant, Pariparoba].
AB  - Four known compounds have been isolated from the aerial parts of the Brazilian
      medicinal plant Pariparoba (Pothomorphe umbellata). They were an alkaloid, a
      flavone, a dihydrocalcone, and a steroid. The chemical structures were
      established to be N-benzoylmescaline, wogonin, uvangoletin, and beta-sitosterol
      glucoside using spectral methods. Among these compounds, the main component N
      benzoylmescaline showed significant antibacterial activity against Helicobacter
      pylori.

PMID- 11968843
TI  - [Reform of health care in Japan].

PMID- 11968841
TI  - [Measurement of contents in organs of selenium- or vitamin E-deficient rat using
      instrumental neutron activation analysis].
AB  - The contents of iron (Fe), cobalt (Co), zinc (Zn), and selenium (Se) in the
      organs (liver, kidney, spleen, heart, lung, and brain) and the liver cell
      fractions (nuclear, mitochondrial, microsomal, and cytosolic fractions) of Se- or
      vitamin E (VE)-deficient rats were measured using instrumental neutron activation
      analysis (INAA). The contents of Fe in the liver of Se-deficient rats, and in the
      liver and the spleen of VE-deficient rats were increased compared with those in
      normal rats. Fe contents increased mainly in the microsomal fraction. Contents of
      Co in the organs and liver cell fractions of Se- and VE-deficient rats were
      markedly low, reflecting the Co contents in both diets. Contents of Zn in the
      organs and liver cell fractions of Se- and VE-deficient rats decreased to 60-80%
      of the contents in normal rats. The Se contents in Se-deficient rat organs except
      for the kidney, spleen, and brain were below the detectable level under the
      present conditions. Se contents in VE-deficient rat decreased to 50-80% of those
      in normal rats in all organs and fractions. It is suggested that oxidative stress
      due to Se- or VE-deficiency affects the dynamics of Fe and Zn.

PMID- 11968844
TI  - [Treatment strategies for viral hepatitis].

PMID- 11968845
TI  - [Genetic analysis of microdissected human tissues].

PMID- 11968846
TI  - [Clinical application of DNA array system in human gastrointestinal cancer].

PMID- 11968847
TI  - [Yeast-based genetic diagnosis and post-genome sequencing].

PMID- 11968848
TI  - [Gene therapy and regenerative medicine].

PMID- 11968849
TI  - [Establishment of a business associated with DNA microarray in Hokkaido].

PMID- 11968850
TI  - [Genetically engineered mice and its application to bioindustry].
AB  - More than 2 decades have past since the first transgenic mouse was created. In
      this review we will focus on recent technologies in the field of mouse genetic
      engineering and on its application to bioindustry. The most important milestone
      in this field was the invention of the gene targeting technique. Recent
      improvement of this technique to conditional gene targeting together with the
      Cre/IoxP system further encouraged the generation of mutant mice. It is obvious
      that there will be a great demand for some mutant mice as experimental models of
      human disease or as resources of experimental material for basis biological
      research. Thus, creation of such mice would be a rewarding challenge for a
      biological enterprise.

PMID- 11968851
TI  - [A case of positive personal identity of skeletonized remains using lumbar
      radiograph].
AB  - We reported an autopsy case in which premortem and postmortem radiographs of the
      spine were available for comparison and provided a basis for making an
      identification. As the elderly often lives alone and has no relatives, one of our
      tasks is sometimes ascertaining the personal identity of him or her. Osteophytes
      of the vertebra are valid for establishing a positive personal identification in
      human remains.

PMID- 11968852
TI  - Amelioration of cerulein-induced acute pancreatitis by 2,2'-dipyridyl in rats.
AB  - We studied the effect of iron chelators, 2,2'-dipyridyl and desferrioxamine, on
      cerulein-induced pancreatitis in rats. Acute pancreatitis was induced by a single
      subcutaneous injection of 100 micrograms/kg body weight of cerulein, which caused
      hyperamylasemia and edematous pancreatitis with neutrophilic infiltration. Blood
      samples were collected for determination of serum amylase values and the pancreas
      was removed for the histological examination 6 h after the cerulein injection.
      Intraperitoneal administration of a ferrous iron chelator, 2,2'-dipyridyl, prior
      to the cerulein injection resulted in amelioration of hyperamylasemia and
      histological abnormalities such as edema and inflammation but not of acinar cell
      vacuolization. In contrast, administration of a ferric iron chelator,
      desferrioxamine, did not show any beneficial effects. These results indicate that
      administration of 2,2'-dipyridyl ameliorates the pancreatitis induced by the
      supramaximal dose of cerulein.

PMID- 11968853
TI  - [Impact of stress response genes induced by L-glutamine on warm ischemia and
      reperfusion injury in the rat small intestine].
AB  - L-Glutamine (Gln) is known to have protective effect on the small intestine under
      deleterious stressful condition. Although the mechanism by which Gln confers
      intestinal cellular protection remains unclear, its potential role may be
      mediated via signal transduction including stress response genes and anti
      apoptotic genes. Herein, we examined a possible role of stress response genes in
      warm ischemically injured small intestines. We measured mRNA and protein
      expression of heme oxygenase (HO)-1, Bcl-2 and Bax at different time points after
      Gln administration. Warm ischemia model was made by clamping of the superior
      mesenteric artery for 60 min. After reperfusion, tissue samples were taken for
      end labeling of nuclear DNA fragments (TdT-mediated d-uridine triphosphate biotin
      nick end labeling; TUNEL) and hematoxylin-eosin staining. In Gln-treated group,
      the substantial expression of HO-1 mRNA peaked at 3 h and reduced thereafter,
      while HO-1 protein synthesis was noted within 3 h and reached plateau thereafter.
      NO-1-positive components were markedly detected in the villus epithelial cells
      and crypts. The ratios of Bcl-2/Bax mRNA expression after Gln administration
      peaked at 3 h and reduced thereafter until 24 h. Bcl-2 immunoreactive protein was
      enhanced in Gln group, whereas Bax was faintly detected. Following reperfusion,
      less TUNEL-positive staining of the top of the villi and more prompt recovery of
      denuded villus epithelial cells were noted in Gln group, compared with those in
      untreated and lactated Ringer-treated control groups. In conclusion, a
      concomitant expression of anti-oxidative HO-1 and anti-apoptotic Bcl-2 molecules
      induced by non-toxic amino acid, Gln, may alleviate or even prevent intestinal
      warm ischemia and reperfusion injury, attenuating programmed cell death and
      promoting its reepithelialization.

PMID- 11968854
TI  - [Clinical significance of serum antibodies against Helicobacter pylori VacA
      protein].

PMID- 11968855
TI  - [Osteopontin can induce cardiopulmonary lesions consisting of macrophage
      infiltration and granuloma formation].

PMID- 11968856
TI  - [The 18th Hokkaido Conference of Pediatric Hematology].

PMID- 11968857
TI  - Recent advances in otitis media. 9. Treatment, complications, and sequelae.

PMID- 11968858
TI  - Recent advances in otitis media. 2. Epidemiology, natural history, and risk
      factors.

PMID- 11968859
TI  - Recent advances in otitis media. 3. Middle ear physiology and pathophysiology.

PMID- 11968860
TI  - Recent advances in otitis media. 4. Anatomy, cell biology, pathology, and animal
      models.

PMID- 11968861
TI  - Recent advances in otitis media. 5. Molecular biology and biochemistry.

PMID- 11968862
TI  - Recent advances in otitis media. 6. Microbiology and immunology.

PMID- 11968863
TI  - Recent advances in otitis media. 1. Definitions, terminology, and classification
      of otitis media.

PMID- 11968864
TI  - Recent advances in otitis media. 7. Vaccine.

PMID- 11968865
TI  - Recent advances in otitis media. 8. Diagnosis and screening.

PMID- 11968866
TI  - Eight months left. How will HIPAA really affect my practice?

PMID- 11968867
TI  - Protecting our antibiotic lifeline.

PMID- 11968868
TI  - Michigan's health status. Can't we do better?

PMID- 11968869
TI  - Michigan ranks 38th in infant mortality. Why and what's being done?

PMID- 11968870
TI  - Understanding "lost opportunity cost". How it effects your financial health.

PMID- 11968871
TI  - Doctors go digital.

PMID- 11968872
TI  - Medical liability claims frequency and severity on the rise.

PMID- 11968873
TI  - Listening. The foundation of personal and professional satisfaction.

PMID- 11968874
TI  - Is your practice ready for the big three?

PMID- 11968875
TI  - MSMS Alliance flexes muscle in legislative arena.

PMID- 11968876
TI  - The facts about antibiotics.

PMID- 11968877
TI  - Medical records.

PMID- 11968878
TI  - Understanding completion entailments in the absence of agency cues.
AB  - This study investigated the role that agency information plays in children's
      early interpretations of grammatical aspect morphology, in particular, the
      progressive -ing and simple past forms. Fifty-nine children (two-, four- and five
      year olds) were presented with a forced-choice sentence-to-scene matching task
      very similar to the one used by Weist and colleagues (Weist, 1991; Weist, Wysocka
      & Lyytinen, 1991; Weist, Lyytinen, Wysocka & Atanassova, 1997), except that here
      the scenes contained only information about the relative completion of the object
      of the event and no information about the state of the agent of the event. In
      contrast to previous research, the children here did not succeed at this object
      oriented task until as late as age five; moreover, also contra previous work,
      when they did succeed, their performance tracked the formal entailments of
      grammatical aspect. Thus, subjects consistently matched the perfective sentence
      to the completed event (reflecting the perfective's entailment of completion) but
      never consistently matched the imperfective sentence to either scene (reflecting
      the imperfective's lack of entailments). It is argued that agent-oriented
      meaning, in particular, intentionality, has priority in the mapping process over
      object-oriented completion entailments.

PMID- 11968879
TI  - The creation of new figurative expressions: psycholinguistic evidence in Italian
      children, adolescents and adults.
AB  - According to a developmental model of figurative language acquisition--the global
      elaboration model (Levorato & Cacciari, 1995)--the metalinguistic awareness
      necessary to use figurative language in a creative way is acquired late, and is
      subsequent to the ability to comprehend and produce figurative expressions. One
      hundred and eight children aged 9;6, one hundred and twenty-four children aged
      11;3, one hundred and twelve adolescents aged 18;5 and one hundred adults
      participated in Experiment 1 which studied the development of metalinguistic
      awareness through an elicitation task. The subjects produced a high percentage of
      figurative expressions with a clear developmental trend that is concluded in
      adolescence. In addition, Experiment 2 showed that the production of
      comprehensible, appropriate and novel metaphors, as they were rated by adult
      judges, also increased with age. These results show that the ability to use
      figurative language in a creative and sensible way requires a long developmental
      time span and is strictly connected with the ability to reflect on language as a
      complex cognitive and interpersonal phenomenon.

PMID- 11968880
TI  - Theory and methods in the study of the development of case and agreement: a
      response to Schutze.
AB  - Two recent papers Wexler, Schutze & Rice (1998) and Rispoli (1999a) reach
      different conclusions concerning the relationship between finiteness marking and
      pronoun case errors. Wexler et al. claim they are linked, whereas Rispoli finds
      little evidence for such a linkage. Wexler et al. discounted data from children
      who made pronoun case errors in 100% of their attempts at a subject pronoun,
      whereas Rispoli (1999a) included data from such children. This methodological
      difference may account for our differing conclusions. Schutze (2001) defends the
      omission of these data, claiming that children who make a pronoun case error 100%
      of the time do so because the correct pronoun case form is not in the child's
      productive inventory. Longitudinal data is presented showing the inadequacy of
      this assumption. Children may err without variation after a period of variation,
      indicating that these children have knowledge of the correct form. Apparent
      methodological differences between the two papers reveal deeper theoretical
      biases. The paradigm building approach taken by Rispoli views longitudinal
      variation of this sort as a reflection of lexical retrieval principles at work in
      a developing paradigm. In contrast, the Agr/Tns Omission Model of Wexler et al.
      finds such variation an uncomfortable inconvenience.

PMID- 11968881
TI  - The development of subject-auxiliary inversion in English wh-questions: an
      alternative analysis.
AB  - Rowland & Pine (2000) present an analysis of the development of subject-auxiliary
      inversion in wh-questions in the speech of Adam from the Brown corpus. They show
      that there is an uninversion period in which the child fails to invert the
      subject and auxiliary in wh-questions, and they argue that this is a function of
      the frequency of wh-word + auxiliary collocations in the input: the more frequent
      a particular collocation is in the input, the more likely it is to be inverted in
      the child's speech. In this note an alternative analysis is proposed: the initial
      position of the tensed auxiliary signals interrogative illocutionary force, and
      the auxiliaries which are most reliably inverted are those that are overtly
      tensed morphologically. This analysis not only accounts for Rowland & Pine's data
      but also extends to inversion in yes-no questions. The analysis predicts three
      different patterns for the development of inversion in both types of questions,
      and it is shown that all three are attested.

PMID- 11968882
TI  - Interpretation of relative clauses by young children: another look.
AB  - Interpretation of relative clauses sentences was investigated by having sixteen
      children between the ages of 3;5 and 4;6 act out sentences within four conditions
      that varied the number of potential referents for each noun within the sentence.
      No difference in interpretation accuracy was found between felicitous and
      infelicitous conditions or between biased and neutral conditions. This result
      raises problems for the view that children of this age know the pragmatic
      principles for interpreting relative clauses.

PMID- 11968883
TI  - The syntagmatic-paradigmatic shift and reading development.
AB  - This study examined developmental change in the word association task as reading
      acquisition occurred. Syntagmatic responses follow the stimulus world in
      discourse, 'cold'--'outside', while paradigmatic associates are of the same form
      class, 'cold'--'hot'. Some 59 children were tested three times during the school
      year. The average age of the younger group was 5;4, and the older group, 6;2 at
      the October test. They were given the PPVT, the Woodcock Reading Mastery Test,
      and a word association task. The younger group gave an increasing number of
      rhyming responses and the older group gave more paradigmatic responses as the
      year progressed. Regression analyses with the older group attributed this to
      reading acquisition. The changing nature of the cognitive representation of words
      as reading acquisition took place was discussed.

PMID- 11968884
TI  - Effects of maintaining and redirecting infant attention on the production of
      referential communication in infants with and without Down syndrome.
AB  - The effects of maternal interactive styles on the production of referential
      communication were assessed in four groups of infants whose chronological ages
      ranged between 0;6 and 1;8. Two groups of infants with Down syndrome (DS), one (n
      = 11) with a mean mental age (MA) of 0;8.6, and the other (n = 11) of 1;4.5, were
      matched on MA with two groups (n = 10 each) of typically developing infants.
      Infants were seen bi-monthly, for 8 months, with mothers, same-aged peers, and
      mothers of the peers. Results showed that High MA non-Down syndrome (ND) infants
      produced more words, and High MA DS infants produced more gestures when playing
      with mothers than peers. Mothers exhibited more attentional maintaining
      behaviours than peers, in particular to High MA infants, but they redirected the
      attentional focus of Low MA infants more. Sequential loglinear analyses revealed
      interesting contingencies between the interactive strategies of mothers and the
      referential communicative behaviours of their infants. Whereas maintaining
      attention increased, redirecting attention decreased the likelihood of the
      production of gestures and words in children. However, redirecting attention was
      followed by maintaining attention. Thus, mothers redirect the attentional focus
      in order to promote joint attention and referential communication. Furthermore,
      words and gestures of the children also promote joint attention in mothers. This
      highlights the reciprocal nature of these dynamic communicative interactions.

PMID- 11968885
TI  - Caregiver attention-focusing and children's attention-sharing behaviours as
      predictors of later verbal IQ in very low birthweight children.
AB  - Specific relationships between verbal and nonverbal aspects of caregiver
      attention-focusing events and later verbal IQ were investigated for a risk sample
      of 26 very low birthweight [VLBW], preterm [PT] children. Videotaped interactions
      between VLBW, PT children at 2;0 and their caregivers were coded for caregiver
      attention-focusing speech and/or caregiver attention-focusing gestures (display,
      demonstration and pointing), caregiver gesture-speech combinations, and for child
      attention-sharing through gesture and social gaze. To investigate the specific
      effects of caregiver and child interactional factors, analyses statistically
      controlled for cognitive status. Simultaneous multiple regression analyses found
      that overall caregiver attention-focusing involving gesture, child attention
      sharing behaviours, and cognitive status each significantly and uniquely
      contributed to verbal IQ at 3;0. Further analyses contrasted the contributions of
      caregiver gesture with relevant descriptive speech, caregiver gesture with no
      speech/nondescriptive speech, and caregiver pointing. Results of these analyses
      suggest that caregiver gesture with relevant descriptive speech makes a unique
      and positive contribution to later language performance.

PMID- 11968886
TI  - Singular or plural? Children's knowledge of the factors that determine the
      appropriate form of count nouns.
AB  - Two experiments investigated the factors that govern children's use of singular
      and plural forms of count nouns. Experiment 1 used an elicited production task to
      investigate whether children use referential and/or syntactic information to
      determine the form of the count nouns when the two sources of information
      conflict (e.g. each x, one of the xs), as well as when the linguistic context
      does not provide any constraint on the form of the noun, but the referential
      context does (e.g. the dog(s)). 48 children, aged 1;9 to 5;6, participated in
      Experiment 1. The results suggest that even the youngest children can use
      referential information when relevant, and can ignore referential information
      when necessary. Children did, however, show a tendency to make errors with the
      quantifier each in non-partitive contexts, and a developmental trend was found in
      the use and avoidance of each in non-partitive contexts. Experiment 2, an act out
      task, provided a second test of the role of referential information in children's
      use of singular and plural forms. Experiment 2 also investigated children's
      appreciation of the semantic distinction between each and all. 48 children, aged
      1;8 to 5;6, participated in Experiment 2. A weak sensitivity to the semantic
      distinction between the two quantifiers as well as the syntactic context in which
      they were used was found. The results of the two experiments suggest that, from
      the beginning, children approach the task of learning when to use singular and
      plural forms of count nouns on the basis of morphosyntactic, semantic, and
      referential properties of utterances, rather than initially using only one of
      these types of information.

PMID- 11968887
TI  - Does error-free use of French negation constitute evidence for Very Early
      Parameter Setting?
AB  - Many recent generativist models attribute grammatical knowledge to young children
      on the basis that children's language patterns the same way as the target adult
      language. It has been proposed that the child acquires this knowledge early on in
      development by a process of parameter setting. Wexler (1996) presents the very
      early parameter setting hypothesis (VEPS), which suggests that basic language
      specific parameters are set correctly at the earliest observable stages, that is,
      from the onset of multi-word speech. However, the patterns predicted by VEPS are
      necessarily a characteristic feature of the input language and could therefore be
      just as readily explained in more limited scope term. A good example of this is
      French negation where, in order to perform correctly, the child simply has to
      register that certain lexical forms precede the negative particle pas and certain
      other forms follow it. One implication of such a limited scope account is that
      there should be a strong relation between the lexical specificity of children's
      and mothers' use of verbs before and after pas. We present data for one subject,
      aged from 2;1 to 2;8, that are compatible with this hypothesis. While these data
      do not count directly against VEPS, they do suggest that the very low frequency
      of errors in children's use of French negation does not in and of itself
      constitute evidence for early syntactic knowledge.

PMID- 11968888
TI  - Italian children's understanding of the epistemic and deontic modal verbs dovere
      (must) and potere (may).
AB  - This study assesses children's understanding of the Italian modal verbs dovere
      (must) and potere (may) in their dual function of qualification of the speaker's
      beliefs (epistemic modality) and behaviour regulation (deontic modality). 192
      children and 60 adults participated in the experiment. Children aged 3;0 to 9;2
      were presented with two tasks: one assessed their understanding of modal
      expressions in the epistemic domain--looking for an object by following the
      information contained in a sentence; the other assessed their understanding of
      modal expressions in the deontic domain--acting according to obligations,
      permissions and prohibitions in the context of a game. Half of the subjects
      carried out the tasks in a single-sentence format and half carried out the tasks
      in a double-sentence format. In the single-sentence format the subjects had to
      follow the directions supplied by a modalized sentence; in the double-sentence
      format they had to follow the directions supplied by the sentence containing the
      stronger modal verb. Our results show that the understanding of deontic modal
      forms precedes the understanding of epistemic modal forms and that a full
      understanding of the strength of different modal forms is achieved only at eight
      years.

PMID- 11968890
TI  - Home is where the heart is.

PMID- 11968889
TI  - Creating an ostomy product formulary.

PMID- 11968891
TI  - $20 million invested in nursing's future.

PMID- 11968892
TI  - Healing shingles with moist occlusive dressings.

PMID- 11968893
TI  - Chronic fall risk among aged individuals with type 2 diabetes.
AB  - Falls in the elderly are common and a frequent source of injury. Chronic fall
      risk factors were evaluated in aging individuals with type 2 diabetes from two
      different settings--an urban day care center (age range: 57 to 83 years) and a
      rural community center (age range: 62 to 97 years). Six fall-related risk factors
      were studied: client history/subjective assessment of fall history, daily
      medication intake, number of medical diagnoses, balance (Tinetti Balance and Gait
      Tool), lower extremity protective sensation (Semmes-Weinstein monofilament
      testing), and relaxed gait velocity (timed functional walk test). Both groups
      demonstrated a high risk for chronic falling with a mean of 4.8 and 4.0 risk
      factors present in individuals from the urban day care center and the rural
      community center, respectively. No differences between clients in the two centers
      with respect to number of medications and comorbidities were found. In both
      groups, > 50% of individuals reported a history of falling. Loss of protective
      sensation was detected in 100% of the individuals from the urban day care center
      compared to 67% in the rural community center. Similarly, 40% of the individuals
      from the urban day care center demonstrated impaired balance as compared to 29%
      from the rural community center. A similar ratio of impaired balance to loss of
      lower extremity protective sensation was demonstrated across the two groups.
      These data indicate a potential relationship between loss of protective sensation
      and impaired balance. These findings also indicate that individuals in urban and
      rural community settings share similar risk factors for chronic falling.

PMID- 11968894
TI  - Noncontact normothermic wound therapy and offloading in the treatment of
      neuropathic foot ulcers in patients with diabetes.
AB  - Foot ulcerations secondary to diabetes have been implicated as a leading cause of
      amputations worldwide. Prompt healing of ulcerations can prevent many of these
      amputations and improve the quality of life for affected individuals. Improving
      blood supply and reducing ambulatory pressure on the plantar surface of the foot
      have been demonstrated to greatly improve limb salvage. A controlled clinical
      study was conducted to ascertain the effect of a noncontact, radiant warming
      device designed to increase wound temperature and improve tissue oxygenation.
      Thirty-six (36) patients with neuropathic foot wounds secondary to diabetes were
      assigned to management with offloading and warming (treatment) or offloading
      therapy only (control) for a period of 8 weeks or until healing. Individuals in
      the warming group were treated daily for 3 hours with the warming device. Wounds
      healed at a rate of 0.019 cm2 (+/- 0.019 cm2/day in the control group, P < 0.05).
      These results support the clinical use of noncontact radiant warming and
      offloading in the management of neuropathic ulcers in people with diabetes.

PMID- 11968896
TI  - Removing the "un" from the law of unintended consequences.

PMID- 11968895
TI  - Pressure ulcers in nursing homes: does negligence litigation exceed available
      evidence?
AB  - Nursing homes today face an increasing amount of oversight as they comply with
      regulations from federal, state, and local governments and agencies. The trend of
      judicial oversight, particularly in cases involving pressure ulcers, presents a
      unique set of challenges to the nursing home industry. The standards of care that
      are increasingly applied to establish the incidence of negligence in relevant
      cases are dependent on an under-researched area of the clinical phenomenon of
      skin breakdown within a frail elderly population. As the nursing home population
      continues to grow and resources are further strained, finding ways to best
      utilize resources becomes imperative. Consideration must be given to the growing
      body of evidence indicating that some patients are incapable of mounting a
      "normal" response to the physical forces responsible for the damage observed with
      pressure ulcers. Pressure ulcers have evolved to the status of being a synonym
      for neglect and/or abuse. Clinicians must focus on establishing a realistic and
      far more nuanced body of knowledge regarding pressure ulcers among the frail
      elderly.

PMID- 11968897
TI  - Prevalence and incidence study sparks issues.

PMID- 11968898
TI  - Scanning electron microscopic description of cellular activity and mineral
      changes in feline odontoclastic resorptive lesions.
AB  - The cellular activity and changes in mineral composition of dental tissues
      involved in feline odontoclastic resorptive lesions were investigated. Teeth with
      at least 1 lesion (n = 10) were extracted from 10 different cats that were
      presented primarily for chronic gingivostomatitis and/or severe periodontal
      disease. Scanning electron microscopic methods were used to determine the
      presence of resorptive cells in 8 teeth while 2 teeth were evaluated for
      pathologic changes in dental mineral composition. Observations were complicated
      by the presence of organic wear on the dental surfaces, however resorptive cells
      could be clearly identified in feline odontoclastic resorptive lesions.
      Resorptive cells had morphologic features indicative of "osteoclast-like" cells
      or odontoclasts. Resorptive cell activity created a resorption area of darker
      dentin continuous with physiologic dentin. The darker dentin area seemed poorly
      mineralized and showed a significantly lower calcium/phosphorous ratio compared
      with adjacent physiologic denting in 1 tooth. A significantly higher level of
      magnesium combined with available carbonate ions may have increased the
      solubility in areas of darker dentin.

PMID- 11968899
TI  - Clinical and microbiological effects of oral zinc ascorbate gel in cats.
AB  - The clinical and microbiological effects of zinc ascorbate gel applied orally in
      cats were evaluated during a 42-day study period. Cats were divided randomly into
      two equal groups, with the treatment group (18 cats) receiving zinc ascorbate gel
      and the control group (18 cats) receiving a placebo (0.9% sterile saline).
      Clinical parameters evaluated biweekly included halitosis, plaque, calculus, and
      gingivitis. Aerobic and anaerobic bacterial cultures were obtained from cats in
      the treatment group at Days 0 and 42. There was a significant decrease in plaque,
      gingivitis, and anaerobic periodontal pathogens in treatment group cats.
      Halitosis and calculus scores were not significantly different in treatment group
      compared with control group cats. The results of this study suggest that zinc
      ascorbate gel used as an oral antiseptic improves feline oral health, and may be
      most effective in decreasing bacterial growth, plaque formation, and gingivitis
      when applied following a professional teeth cleaning procedure.

PMID- 11968900
TI  - Free tissue transfer of the rectus abdominis myoperitoneal flap for oral
      reconstruction in a dog.
AB  - A five-month-old intact/male Boxer dog was presented 5-days following bite wound
      trauma to the maxillary region resulting in an oronasal fistula extending from
      the maxillary canine teeth to the soft palate. Multiple surgical procedures using
      local, buccal mucosal flaps failed to repair the oronasal fistula. Free tissue
      transfer of the rectus abdominis myoperitoneal flap using microvascular surgical
      techniques was successful in providing soft tissue reconstruction of the hard
      palate area. Complications of these surgical techniques included muscle
      contraction and subsequent muzzle distortion. Small, refractory oronasal fistulae
      at the perimeter of the myoperitoneal flap were repaired by primary wound
      closure.

PMID- 11968901
TI  - Squamous cell carcinoma associated with extraction of a maxillary canine tooth in
      a dog.

PMID- 11968902
TI  - Crown lengthening for mandibular and maxillary canine teeth in the dog.

PMID- 11968903
TI  - Vital pulp therapy for complicated crown fracture of permanent canine teeth in
      dogs: a three-year retrospective study.
AB  - A 36-month retrospective study compared the results of vital pulp therapy based
      on the duration of pulp exposure for complicated crown fracture of 97 permanent
      canine teeth in 76 dogs. Postoperative oral and radiographic examinations were
      performed at 3, 12, and 36-months following treatment. Based on the 36-month
      postoperative examinations 88.2%, 41.4 %, and 23.5% of teeth were vital when
      treated within 48-hours, 1-week, and 3-weeks of pulp exposure, respectively.
      There was a significant difference in the incidence of tooth vitality between
      groups. The duration of pulp exposure following complicated crown fracture
      influenced the success of vital pulp therapy. Vital pulp therapy should be
      performed as soon as possible following traumatic pulp exposure.

PMID- 11968904
TI  - Assessment of vital pulp therapy for nine complicated crown fractures and fifty
      four crown reductions in dogs and cats.
AB  - Subjective owner assessment of the success of vital pulp therapy was performed
      for complicated crown fracture (n = 9) and crown reduction (n = 54) of canine
      teeth in dogs and cats. Our results documented that owners are not able to
      accurately determine the outcome of vital pulp therapy. Objective assessment of
      vital pulp therapy for teeth receiving crown reduction indicated maintenance of
      vitality in 28 of 28 (100%) teeth. Subjective and objective assessments of vital
      pulp therapy performed > 7-days following complicated crown fracture indicated 9
      of 9 (100%) teeth were non-vital. A poor prognosis for maintenance of tooth
      vitality is warranted for vital pulp therapy of complicated crown fractures with
      prolonged pulp exposure regardless of the age of the patient. Whereas, an
      excellent prognosis can be provided for vital pulp therapy following crown
      reduction. Semiannual, postoperative oral and radiographic examinations are
      recommended for a minimum of 2-years to assess vitality in all teeth receiving
      vital pulp therapy.

PMID- 11968905
TI  - Island palatal mucoperiosteal flap for repair of oronasal fistula in a dog.
AB  - A two-year-old neutered/male mixed-breed dog had received partial maxillectomy
      for fibrosarcoma. An oronasal fistula occurred as a complication of the surgical
      procedure. An island palatal mucoperiosteal flap was developed and rotated to
      repair the oronasal fistula. Acute (1-month) and long-term (8-months) follow-up
      indicated appropriate healing of the transposed island palatal mucoperiosteal
      flap with resolution of clinical signs indicative of oronasal fistula.

PMID- 11968906
TI  - Dental-related facial swelling in a cat.

PMID- 11968907
TI  - Vital pulp therapy.

PMID- 11968908
TI  - Localized intrinsic staining of teeth due to pulpitis and pulp necrosis in dogs.
AB  - Dental charts and records of 71 dogs were received and 84 intact tooth crowns
      were noted to have been entirely discolored in shades of pink, purple, grey, or
      tan. Endodontic therapy was performed on 49 of these teeth allowing gross
      examination of the entire pulp. In exploratory pulpotomy was performed in 15
      teeth prior to exodontic therapy in order to assess the integrity of the coronal
      pulp. Gross signs of partial or total pulp necrosis were present in 59 (92.2%) of
      these teeth. The pulp was not observed grossly in 20 teeth which received
      exodontic therapy. Overall, of the 84 teeth evaluated, 36 (42.9%) had no
      radiographic signs of endodontic disease. Gross or radiographic signs of
      endodontic disease were absent in only 2 (4.1%) discolored teeth receiving
      endodontic therapy. Based on the low incidence of vital, affected teeth in the
      dogs of this study, endodontic on exodontic therapy is recommended for discolored
      teeth.

PMID- 11968909
TI  - Treatment of mandibular first molar teeth with endodontic-periodontal lesions in
      a dog.
AB  - A two-year-old spayed/female Miniature Pinscher was treated for mobility of the
      left and right mandibular first molar teeth. Periodontal probing and intraoral
      dental radiographs indicated severe periodontal attachment loss. It was
      determined that both teeth had endodontic-periodontal lesions based on
      restoration of periodontal attachment and partial resolution of radiolucent
      periapical lesions following treatment which emphasized endodontic therapy.

PMID- 11968910
TI  - Infundibular decay in equine maxillary teeth.

PMID- 11968911
TI  - Morphologic features of the root canal system of the maxillary fourth premolar
      and the mandibular first molar in dogs.
AB  - Root canal morphology was evaluated in 72 maxillary fourth premolar and 59
      mandibular first molar teeth. An apical delta was present in all roots (n = 334).
      The apical delta represented approximately 12-18% of the total root length for
      all roots. Non-apical ramifications from the main canal were observed in 25.1% of
      roots. Secondary canal(s) were present in 20.6% of roots, while lateral canal(s)
      were present in 6.9% of roots. The distal root of the maxillary fourth premolar
      had the highest incidence (47.2%) of non-apical ramifications. Overall, 68.0 and
      20.4% of maxillary fourth premolar and mandibular first molar teeth had non
      apical ramifications, respectively. The prevalence and location of non-apical
      ramifications may influence clinical decision making when performing endodontic
      therapy.

PMID- 11968912
TI  - Behind the scenes of the JVD.

PMID- 11968913
TI  - Effectiveness of an enzymatic rawhide dental chew to reduce plaque in beagle
      dogs.
AB  - Tooth brushing is considered a superior technique for reducing plaque
      accumulation. Other methods of maintaining oral hygiene have been investigated
      since many owners may not be willing or able to brush their dog's teeth.
      Following a professional teeth cleaning procedure, 11 dogs were offered a rawhide
      dental chew BID for 7-days, while 11 other dogs were fed the same diet without
      receiving the chew device. Dogs in the treatment group had significantly less
      plaque formation during the trial period compared with dogs in the control group.
      The rawhide dental chew provided in the study reported here decreases plaque
      formation in the short-term and may be beneficial in the prevention of
      progressive periodontal disease associated with attachment loss if provided on a
      long-term basis.

PMID- 11968914
TI  - Mandible and mandibular first molar tooth measurements in dogs: relationship of
      radiographic height to body weight.
AB  - Height measurements of the mandible and the mandibular first molar tooth were
      obtained from 234 dogs. Statistical analysis was performed to determine possible
      associations between these measurements and body weight, sex, age, and body
      condition. There was a statistically significant association between the
      mandible: mandibular first molar tooth height measurement ratio and body weight
      (p < 0.0001) in all body weight groups. Small dogs had proportionally larger
      mandibular first molar teeth relative to mandibular height compared with larger
      dogs. This relationship may contribute to an increased susceptibility in small
      dogs for periodontitis and subsequent tooth loss. There was no statistically
      significant association between the mandible: mandibular first molar tooth height
      measurement ratio and other parameters evaluated in this study.

PMID- 11968915
TI  - Facial swelling associated with impaction of the deciduous and permanent
      maxillary fourth premolars in a dog with patent ductus arteriosus.
AB  - A three-year-old Labrador retriever was referred for decreased appetite, a
      painful swelling in the region of the maxillary right fourth premolar, and a
      heart murmur indicative of patent ductus arteriosus (PDA) diagnosed 1.5-weeks
      prior to presentation. Oral examination and intraoral dental radiographs showed
      impaction of the maxillary right fourth premolar surrounded by reactive alveolar
      bone. Necrotic bone, remnants of the deciduous maxillary right fourth premolar,
      and the impacted permanent maxillary right fourth premolar were removed following
      surgical exploration of the area. The PDA was repaired without complication 2
      weeks following oral surgery. The extraction site was healing appropriately, and
      the dog's inappetence and painful facial swelling had resolved.

PMID- 11968916
TI  - Malocclusion in a cat.

PMID- 11968917
TI  - Oral and maxillofacial reconstruction in a cat using wire and acrylic.
AB  - A 15-month-old DSH cat was presented with facial deformity secondary to multiple
      oral and maxillofacial fractures after being struck by an automobile. Multiple
      wires and dental acrylics were used for fracture repair.

PMID- 11968918
TI  - Odontoclastic resorptive lesion of a mandibular right first molar in a cougar.
AB  - A two-year old neuteral/male cougar (Felis concolor) was presented because of
      abnormal eating habits and an irregularity of the mandibular right first molar
      that was noted by the caretaker. Oral examination and dental radiographs showed a
      lesion consistent with odontoclastic resorption of the mandibular right first
      molar, and a crown fracture and dilacerated root of the maxillary right first
      incisor. Exodontic therapy was performed on both teeth. The caretaker reported no
      problems associated with the patient's oral cavity 10-months following treatment.

PMID- 11968920
TI  - Transoral foreign body in a cat.

PMID- 11968919
TI  - Proliferative gingival lesion in a cat with disseminated cryptococcosis.
AB  - A case of disseminated cryptococcosis with oral, pulmonary, and cutaneous
      manifestations is described in an eleven-year-old Siamese cat. Marked clinical
      improvement was noted 2-months following appropriate antifungal therapy. A review
      of disseminated cryptococcosis and the oral manifestations of fungal disease are
      provided.

PMID- 11968921
TI  - Comparison of two heated gutta percha and sealer obturation techniques in canine
      teeth of dogs.
AB  - The overall endodontic fill and apical seal achieved using two different
      obturation methods were compared. Twenty-six adult dog canine teeth were
      instrumented and obturated using either a warm vertical or heated lateral
      technique. Zinc oxide-eugenol sealer was applied by paper point in the warm
      vertical technique and by syringe injection in the heated lateral technique. The
      cadaver jaws were warmed to 35-37 degrees C (95-98.6 degrees F) during obturation
      using a circulating warm water bath. Obturation times were recorded and
      ventrodorsal, lateral, and oblique dental radiographs were taken of all teeth for
      comparison. Twenty-two of the canine teeth were extracted and an apical dye study
      was performed using a clearing technique. Apical dye leakage was linearly
      measured to evaluate the furthest ink penetration into the root canal. Although
      radiographically the heated lateral method appeared to have a better endodontic
      fill, there was significantly greater apical dye leakage in teeth obturated with
      that combination of sealer and gutta percha. There was also extrusion of sealer
      and root fracture associated with the heated lateral technique. The method of
      sealer application was different for each technique; this variable should be
      taken into consideration when interpreting our results, which suggest that the
      warm vertical compaction technique may provide a better apical seal in canine
      teeth of dogs in a shorter period of time, with fewer obturation complications
      when compared to the heated lateral technique.

PMID- 11968922
TI  - Effects of ultrasonic dental scaling on pulp vitality in dogs: an experimental
      study.
AB  - We investigated whether dental pulpal damage is produced as a result of the
      application of an ultrasonic scaler commonly used in clinical veterinary
      dentistry. Using methods developed in preliminary studies, we examined six dogs.
      The radiographic thickness of the dentin and pulp cavity was measured. The
      ultrasonic scaler was applied to maxillary and mandibular premolar teeth for 30,
      60, or 90 seconds, without the use of water as a coolant. The temperatures of the
      room, the pulp canal on untreated incisor teeth, the cheek, the gingival sulcus,
      and the dentin of the affected teeth were recorded using a probe with a
      thermistor attached to a resistivity meter and inserted in the dentin to a depth
      of 1 mm. Two weeks following scaling, the teeth were extracted for microscopic
      examination. In another dog serving as a control, the temperature of the dentin
      was increased to between 45 degrees C (113 degrees F) and 47 degrees C (117
      degrees F) and the premolar teeth were removed for microscopic examination 15
      days later. We concluded that the application of an uncooled ultrasonic scaler
      for 90 seconds did not increase the temperature of the dentin. However, damage
      comparable with acute pulpitis resulted as a consequence of the ultrasonic
      effect, similar to the effects produced by the 45-47 degrees C heat applied in
      the control animal.

PMID- 11968923
TI  - Surgical exposure and orthodontic extrusion of an impacted canine tooth in a cat:
      a case report.
AB  - A 7 month-old, male domestic shorthaired cat was referred because of facial
      swelling, an operculated cystic oral mass, and impaction of the associated
      maxillary left canine tooth. Surgical exposure and realignment failed to result
      in eruption. Surgical reexposure and orthodontic extrusion resulted in a
      functional alignment of the tooth within the dental arch. Follow up evaluations
      over the 5 ensuing years indicated persistence of the facial deformation, no
      evidence of ameloblastic biotransformation, and a healthy tooth.

PMID- 11968924
TI  - Extraction and abscess treatment in a rabbit.

PMID- 11968925
TI  - Ultrasonic debridement and proper home care.

PMID- 11968926
TI  - Ultrasonic debridement and proper home care.

PMID- 11968927
TI  - Prevention of bacteremia in dogs undergoing dental scaling by prior
      administration of oral clindamycin or chlorhexidine oral rinse.
AB  - Dogs with periodontitis were used to determine the efficacy of an oral regimen of
      clindamycin versus chlorhexidine acetate oral rinse in reducing the total number
      of bacteria and the incidence of bacteremia before and after dental scaling.
      Aerobic and anaerobic bacteria, isolated from blood and gingival swab cultures,
      were identified to genus using an automated system.

PMID- 11968928
TI  - Comparison of the effects of four different power scalers on enamel tooth surface
      in the dog.
AB  - The surface roughness of tooth enamel was quantitatively evaluated following
      scaling with four power scalers at three different tip forces. Ceramic and tooth
      samples were evaluated for surface roughness using surface profilometry. Applied
      tip forces were produced with a horizontal balanced arm holding the scaler
      handpiece and load weight, and were measured using a load cell. The power scalers
      evaluated were the ultrasonic piezoelectric, ultrasonic magnetostrictive
      (ferromagnetic stack), sonic, and rotosonic. For the tooth samples, at 50 grams
      of force, the piezoelectric, magnetostrictive, and sonic scaler roughnesses were
      similar and the rotosonic scaler outcome was statistically higher. Increasing the
      applied force significantly increased the roughness produced by the rotosonic and
      piezoelectric scalers. The results of this study indicate that the type of power
      scaler and applied tip force used determines the post-scaling surface roughness
      of ceramic and tooth enamel surfaces.

PMID- 11968930
TI  - Simultaneous hyperplasia, metaplasia, and neoplasia in an 8 year-old boxer dog: a
      case report.
AB  - Generalized gingiva hyperplasia and multiple gingival masses were observed in an
      8 year-old boxer dog. The masses were removed surgically. Three of them were
      biopsied. Microscopic examination was reported as fibrous gingival hyperplasia,
      fibrous epulis with osseous metaplasia, and mast cell tumor. Twenty-two months
      following surgery, moderate generalized gingival hyperplasia was present, with no
      clinical evidence of regrowth of the neoplasms.

PMID- 11968929
TI  - Isolation of oral spirochetes from dogs and cats and provisional identification
      using polymerase chain reaction (PCR) analysis specific for human plaque
      Treponema spp.
AB  - Identification of plaque spirochetes from dogs is rare and no studies to date
      report cultivation of canine or feline plaque spirochetes. Plaque samples
      obtained from canine and feline patients were cultured in broth media.
      Spirochetes cultured were subjected to microscopic evaluation and were cloned on
      a solid medium. The clones were provisionally identified using species-specific
      PCR for treponema isolated from human plaque. Canine spirochete clones included
      Treponema denticola, T. socranskii ssp., T. vincentii, T. maltophilum, T. medium,
      and T. pectinovorum. Feline clones included T. maltophilum and T. socranskii. Non
      amplified clones may represent novel treponemes. Future studies will be aimed at
      comparison of the spirochetes present in dogs and cats with or without
      periodontal disease.

PMID- 11968931
TI  - Periodontal disease in two dogs.

PMID- 11968932
TI  - Taking the pulse: the beat goes on.

PMID- 11968933
TI  - Taking the pulse: the beat goes on.

PMID- 11968934
TI  - Fractured maxillary premolar tooth.

PMID- 11968935
TI  - Elephant tusks: where are the nerves?

PMID- 11968936
TI  - Misuse of Dremel tool in equine dentistry.

PMID- 11968937
TI  - Dental and craniofacial findings in eight miniature schnauzer dogs affected by
      myotonia congenita: preliminary results.
AB  - Myotonia is a clinical sign characterized by the delay of skeletal muscle
      relaxation following the cessation of a voluntary activity or the termination of
      an electrical or mechanical stimulus. Recently, Miniature Schnauzers with
      myotonia congenita associated with defective chloride ion conductance across the
      skeletal muscle membrane were identified. Congenital myotonia in these dogs
      appears to follow an autosomal recessive mode of inheritance. Craniofacial and
      dental findings of eight Miniature Schnauzer dogs with myotonia congenita are
      described in the present paper. These findings include: delayed dental eruption
      of both deciduous and permanent dentition: persistent deciduous dentition;
      unerupted or partially erupted permanent teeth: crowding and rotation of premolar
      and or incisor teeth: missing teeth: increased interproximal space between the
      maxillary fourth premolar and first molar teeth: decreased interproximal space
      between the maxillary canine and lateral incisor teeth: inability to fully close
      the mouth due to malocclusion: distoclusion: and, decreased mandibular range of
      motion. A long narrow skull with a flattened zygomatic arch and greater
      mandibular body curvature were also consistent findings in the affected dogs. The
      small number of dogs studied prevents conclusive statements about the origin of
      these abnormalities, however it is interesting that only 1 of 45 unaffected
      Miniature Schnauzer dogs showed similar traits.

PMID- 11968938
TI  - Management of a complicated maxillary fourth premolar crown-root fracture in a
      dog.
AB  - A five-year-old spayed/female Border Collie was presented with a crown-root
      fracture of the maxillary left fourth premolar. Surgical endodontic, and
      restorative techniques were performed to maintain the tooth. Re-examination 18
      months following therapy indicated a successful outcome with no radiographic
      signs of periapical pathology.

PMID- 11968940
TI  - Maxillary brachygnathism in an Arab mare.

PMID- 11968939
TI  - Non-immunoglobulin defense factors in canine saliva and effects of a tooth gel
      containing antibacterial enzymes.
AB  - Selected innate: non-immunoglobulin defense factors in canine saliva were
      characterized and quantitated. The samples from dogs showed increased pH, higher
      lysozyme and salivary peroxidase activities, but lower hypothiocyanite
      concentration and myeloperoxidase activity when compared with human saliva.
      Secondly, a 1-month clinical pilot study was performed using a commercial tooth
      gel to determine acute and long-term changes in salivary host defense proteins.
      Daily application of the tooth gel did not substantially affect the
      concentrations of these factors in dogs with normal salivation. Our results
      suggest that canine saliva may be similar to human saliva, comprised of both
      immune and non-immune antimicrobial factors. However, as in humans, oral
      administration of antimicrobial proteins as reported here does not seem to
      benefit dogs with normal saliva secretion. Products such as the tooth gel
      evaluated in this study may benefit dogs with xerostomia or other clinical
      conditions causing decreased saliva production.

PMID- 11968941
TI  - Saprobic potential of Tricholoma matsutake: growth over pine bark treated with
      surfactants.
AB  - Saprotrophic growth of Tricholoma matsutake isolates was investigated over Pinus
      densiflora bark fragments either on soil or on agar media. Preferential
      colonization of pine bark fragments by hyphae, in glucose-deprived environments
      suggested that Matsutake was able to extract some nutrients to sustain its
      growth. This was confirmed in glucose-free liquid nutrient medium, where bark as
      sole carbon source significantly stimulated (up to two-fold) growth of T.
      matsutake isolates. The addition of surfactants (Tween 80 and Tween 40) in liquid
      medium further stimulated mycelium growth over pine bark by up to 55%. Such
      growth stimulation was associated with a sharp increase in protein and beta
      glucosidase excretion by hyphae in culture filtrates. As T. matsutake has some
      saprotrophic ability, the initiation and extension of Matsutake Shiro in forest
      soil might require simultaneously nutrients derived from the host plant and from
      soil organic compounds. Data reported here may contribute to the formulation of
      new culture substrates adapted to the co-culture of T. matsutake and its host
      plant under controlled conditions.

PMID- 11968942
TI  - Importance of the ectomycorrhizal network for seedling survival and
      ectomycorrhiza formation in rain forests of south Cameroon.
AB  - An investigation was undertaken at two sites south Cameroon to assess the
      importance of living roots of adult trees as sources of inoculum for survival,
      ectomycorrhizal colonisation and growth of seedlings of Paraberlinia bifoliolata.
      One-month-old seedlings of Paraberlinia bifoliolata, isolated from or in contact
      with roots of adult target trees, were transplanted in concentric circles 5, 10,
      15, and 30 m away from the stem bases of four adult tree species (Afzelia
      bipindensis, Brachystegia cynometroides, Paraberlinia bifoliolata and
      Tetraberlinia bifoliolata). After 4 and 8 months, survival, ectomycorrhiza
      formation and seedling height were observed; plant biomass was determined after 8
      months. After 4 months, there was no difference in seedling survival between
      seedlings in contact with roots of adult trees and isolated seedlings. The number
      of ectomycorrhizal seedlings was higher among seedlings in contact with adult
      trees than among isolated seedlings. After 8 months, both seedling survival and
      ectomycorrhiza formation were higher in seedlings in contact with roots than in
      isolated seedlings. Seedling survival and ectomycorrhiza formation were highest
      under Brachystegia. The fraction of surviving seedlings that had formed
      ectomycorrhizas was lowest under Afzelia. The fraction of surviving seedlings
      that were ectomycorrhizal declined monotonically towards the edge of the crown
      projection. Biomass of seedlings in contact with adult trees was significantly
      higher than that of isolated seedlings. This difference was consistent for all
      four tree species. The height of seedlings did not vary with the treatment.

PMID- 11968943
TI  - SCAR markers to detect mycorrhizas of an American Laccaria bicolor strain
      inoculated in European Douglas-fir plantations.
AB  - The American strain S238N of the ectomycorrhizal fungus Laccaria bicolor (Maire)
      Orton has been used to inoculate Douglas-fir [Pseudotsuga menziesii (Mir.)
      Franco] plantations in France over the last two decades. Laccaria fruit bodies
      are scarce in mature plantations, which precludes further assessment of its
      persistence by fruit body surveys. Our objective was to develop new markers to
      identify this strain and its eventual non-fruiting progeny on root tips. We
      converted nine random amplified polymorphic DNA markers into sequence
      characterized amplified region (SCAR) markers. Two of these SCAR markers enabled
      us to detect S238N on roots of seedlings and mature trees. No amplification of
      non-fungal (host plant, bacterial, etc.) DNA was observed. Moreover, both SCARs
      were amplified from Laccaria-like mycorrhizas in a Douglas-fir plantation
      inoculated 14 years ago, demonstrating the long-term persistence of the inoculant
      strain. We also obtained a SCAR marker to detect one strain of European origin
      (L. bicolor 81306), indicating that SCARs are potential markers to type the
      naturally occurring genets. Thus, SCAR markers are of great value in studying the
      persistence of inoculant strains and the effects on local populations of
      introducing foreign strains.

PMID- 11968944
TI  - Seasonality of root fungal colonization in low-alpine herbs.
AB  - Arbuscular mycorrhizal (AM) and dark septate endophytic (DSE) fungal colonization
      of Alchemilla glomerulans, Carex vaginata, Ranunculus acris ssp. pumilus and
      Trollius europaeus growing in low-alpine meadows in the Finnish subarctic were
      studied at different times during the growing season. Fungal colonization was
      correlated to soil soluble phosphorus (P) concentration. The influence of flower
      bud removal on fungal colonization was investigated in A. glomerulans, C.
      vaginata and R. acris and the correlation between AM and DSE colonization was
      studied. The fungal colonization patterns were found to be species-specific. R.
      acris maintained a relatively high rate of fungal colonization throughout the
      summer, while the rates of colonization of T. europaeus were lower and decreased
      towards the end of the season. A. glomerulans had constant arbuscular and
      vesicular colonization throughout the summer, but hyphal and DSE colonization
      declined towards the end of the season. C. vaginata did not form arbuscular
      mycorrhiza, but was colonized by DSE fungi and hyaline septate hyphae throughout
      the season. The soil soluble P concentration showed some seasonal variation, but
      was also highly variable between the study sites. Bud removal decreased
      arbuscular colonization of R. acris, but no unique effects were seen in any other
      parameters or the other species studied. The root fungal parameters correlated
      with soil P in some species at some sites, but no consistent trend was found. DSE
      colonization was positively correlated with root vesicular and hyphal
      colonization in some cases. The differences in fungal colonization parameters may
      be related to species-specific phenologies.

PMID- 11968945
TI  - Breaking dormancy is spores of the arbuscular mycorrhizal fungus Glomus
      intraradices: a critical cold-storage period.
AB  - To elucidate the effect of cold storage on spore dormancy in the arbuscular
      mycorrhizal (AM) fungus Glomus intraradices, spores were cold stratified at 4
      degrees C, for either 0, 3, 7, 14, 90 or 120 days, prior to germination tests at
      25 degrees C. The results showed that cold stratification longer than 14 days
      significantly increased spore germination. Moreover, the longer cold storage
      periods clearly reduced spore mortality from 90% to 50% and considerably altered
      the hyphal growth pattern. Long polarized hyphae were only observed after cold
      stratification periods longer than 14 days, involving consequences for root
      infectivity. The results clearly show that environmental factors, e.g., coldness,
      can affect the physiology of AM fungal spores.

PMID- 11968946
TI  - Occurrence of ectomycorrhizal fungi on the forefront of retreating Lyman Glacier
      (Washington, USA) in relation to time since deglaciation.
AB  - Glacier forefronts provide a unique system for studying primary succession of
      plants and fungi. We constructed a chronosequence of ectomycorrhizal fungus
      occurrence on the forefront of Lyman Glacier in the North Cascades mountain range
      in Washington, USA. The plant communities established on non-vegetated substrate
      as patchily distributed plant individuals and developed towards complex
      vegetation with a variety of ectomycorrhizal hosts, including Salix commutata, S.
      phylicifolia, Abies lasiocarpa, Larix lyallii, Pinus contorta, Tsuga mertensiana
      and additional infrequent taxa. A most probable number assay of non-vegetated
      substrates over the chronosequence indicated that ectomycorrhizal propagules were
      few or absent in the non-vegetated areas adjacent to the glacier terminus but
      increased with time since deglaciation. Ectomycorrhizal fungus sporocarps
      occurred as soon as the first host plants of substantial size were present.
      However, none were observed with the most recently established hosts--small A.
      lasiocarpa seedlings. Only four species (Cortinarius decipiens, C. tenebricus,
      Inocybe lacera, and Laccaria cf. montana) occurred on substrate deglaciated for
      less than 40 years. Three of these species (C. tenebricus, I. lacera, and L. cf.
      montana) occurred along the chronosequence to the terminal moraine on substrate
      deglaciated for 70-100 years. An additional five species (one unidentified
      species each of Cortinarius and Lactarius, Cortinarius mutabilis, Lactarius
      uvidus var. montanus, and Suillus cavipes) occurred only on the oldest substrate.
      Our results support the current "early- and late-stage" model of ectomycorrhizal
      fungus succession in that additional species enter the community over time.
      However, we hypothesize that diversification of the mycorrhizal fungus community
      in this primary successional habitat resulted from an increasing diversity of
      host plants along with changing habitat attributes.

PMID- 11968948
TI  - Interactions between indigenous arbuscular mycorrhizal fungi and Aphanomyces
      euteiches in field-grown pea.
AB  - This is the first reported study of the interactions between indigenous
      arbuscular mycorrhizal fungi (AMF) and Aphanomyces euteiches in pea under field
      conditions. A. euteiches was applied to the soil by adding oospores produced in
      vitro. Attempts were made to create a non-mycorrhizal control by incorporating
      carbendazim (Derosal Fl) in the topsoil before sowing. However, all carbendazim
      treated plants showed approximately 20% root colonisation with AMF. Pea plants
      not treated with carbendazim showed a wide variation in AMF colonisation of 35
      70% at the full flowering stage. In these control plots, root length infected
      with oospores of A. euteiches and colonisation by AMF were negatively correlated.
      Application of carbendazim increased the percent root length infected with
      oospores by 50-70%, depending on inoculum density of A. euteiches. Despite the
      lower levels of AMF colonisation in these treated plots, a negative correlation
      with oospore-containing root length was still observed. No correlation was found
      between AMF colonisation and disease severity, disease incidence or pathogen
      enzymatic activity (glucose-6-phosphate dehydrogenase). Thus, AMF do not seem to
      influence the vegetative stage of pathogen development during which cortical root
      rotting takes place, but rather the reproductive stage when oospores are
      produced. The results of this study underline the importance of field experiments
      for validating the significance of mycorrhizal fungi for plant health.

PMID- 11968949
TI  - Cervical intraepithelial changes & HIV infection in women attending sexually
      transmitted disease clinics in Pune, India.
AB  - BACKGROUND & OBJECTIVES: Cervical cancer is the most important cause of
      malignancy associated deaths among women in India. Western studies have reported
      higher risk of abnormal Pap smears in HIV infected women. A large burden of HIV
      infection and increasing HIV epidemic in India threatens to exacerbate incidence
      of cervical cancer. The objective of this study was to assess the frequency of
      Pap smear abnormalities and its association with HIV infection in women attending
      sexually transmitted disease (STD) clinics and to identify associated risk
      factors. METHODS: Between June 1996 and September 1999, women attending two STD
      clinics in Pune were screened for HIV infection, offered STD laboratory diagnosis
      and treatment and their Pap smears were evaluated. RESULTS: Squamous cell
      abnormality was detected in 10 per cent of HIV sero negative women attending STD
      clinics. This proportion was nearly double (19.2%) (Odds ratio = 2.14, 95% C.I.
      1.03-4.48, P = 0.04) in HIV seropositive women. Having more than one life time
      partners and presence of STDs were also significantly associated with Pap smear
      abnormality in univariate analysis. In multivariate analysis, women presenting
      with STD and HIV infection both, were 2.8 times more likely to have inflammatory
      Pap smear and 3.5 times more likely to have abnormal Pap smear compared to HIV
      seronegative women presenting without STDs. INTERPRETATION & CONCLUSION: Pap
      smear abnormalities were common in women attending STD clinics in Pune. Presence
      of HIV infection further increased the risk two-folds. Therefore, women suffering
      from STDs should undergo periodic Pap smear screening for early detection of
      cervical abnormalities and should receive appropriate management to reduce
      morbidity and mortality.

PMID- 11968950
TI  - A study of autoimmune markers in hepatitis C infection.
AB  - BACKGROUND & OBJECTIVES: Hepatitis C virus (HCV) infection is associated with
      several autoimmune markers. Despite HCV being common in India, no information on
      this aspect is available. This study was undertaken to ascertain the frequency
      and clinical significance of autoimmune markers like rheumatoid factor (RF),
      antinuclear antibodies (ANA), antibodies to double stranded deoxyribonucleic acid
      (dsDNA), anti neutrophil cytoplasmic antibody (ANCA), anti smooth muscle
      antibodies (ASMA), anti liver kidney microsomal 1 antibodies (anti LKM1), anti
      gastric parietal cell antibodies (anti GPCA), anti mitochondrial antibodies
      (AMA), anti cardiolipin antibodies (ACL) and cryoglobulins in HCV infection and
      to determine the effect of treatment on these markers. METHODS: Twenty five
      patients with chronic hepatitis C and 25 healthy controls were studied.
      Cryoglobulins were detected by cryoprecipitation, RF by latex agglutination, anti
      dsDNA and ACL by ELISA while indirect immunofluorescence was used to detect all
      other autoantibodies. RESULTS: Eighteen patients (72%) demonstrated autoimmune
      markers. RF, cryoglobulins and anti LKM1 antibodies were the most frequently
      detected markers (in 32% patients each). ASMA, perinuclear ANCA (pANCA), ANA and
      anti GPCA were seen in 24, 20, 12 and 4 per cent patients respectively. None of
      the patients exhibited ACL, AMA or antibodies to dsDNA. No antibodies were
      detected in healthy controls. Sixty per cent of the patients had rheumatological
      symptoms. Of the seven patients followed up after treatment with alpha
      interferon, only two exhibited persistence of RF, while symptoms and other
      markers disappeared. INTERPRETATION & CONCLUSION: Rheumatological symptoms and
      autoimmune markers are common in HCV infection and are usually overlooked.
      Patients with unexplained joint pains and/or palpable purpura should be screened
      for HCV. Further studies are needed to delineate fully the link between infection
      and autoimmunity.

PMID- 11968951
TI  - Changing pattern of biotypes, phage types & drug resistance of Salmonella typhi
      in Ludhiana during 1980-1999.
AB  - BACKGROUND & OBJECTIVES: Ludhiana, an industrial city of Punjab, has a large
      floating population where typhoid has become endemic. A retrospective study was
      carried out over a period of 20 years (1980-1999) at Ludhiana on the biotyping,
      phage typing and drug resistance pattern of Salmonella typhi. METHODS: Of a total
      of 1697 S. typhi isolates obtained, phage typing and biotyping were done of only
      1243 isolates. Antimicrobial susceptibility pattern of these isolates was also
      studied. RESULTS: Of the 1243 S. typhi isolates, 963 (77.5%) and 280 (22.5%) were
      of biotype I and biotype II respectively. Twenty four different S. typhi phage
      types were prevalent in Ludhiana in the past two decades. Between 1980 and 1989,
      more prevalent phage types were phage type A (35%), O (17.6%) and E1 (15.1%).
      During 1990-1999, there was a considerable increase in the incidence of phage
      type E1 (48.1%). The cumulative analysis of past two decades revealed that the
      incidence of phage type E1 (38.8%) was most predominant. In the past one decade
      (1990-1999), 412 S. typhi isolates of 13 different phage types exhibited
      multidrug resistance (MDR) pattern ACCoT (resistant to ampicillin,
      chloramphenicol, co-trimoxazole and tetracycline). High chloramphenicol
      resistance (74.7%) and MDR pattern ACCoT (68.2%) was shown by phage type E1 of S.
      typhi. INTERPRETATION & CONCLUSION: An association was observed between drug
      resistance and phage type pattern of S. typhi as 70 per cent isolates of S. typhi
      phage types E1 and O exhibited ACCoT multidrug resistant pattern. Reemergence of
      chloramphenicol susceptibility in the last decade emphasizes the need for regular
      antimicrobial surveillance to minimize the misuse of these drugs.

PMID- 11968952
TI  - Extended spectrum beta lactamase production & multidrug resistance in Klebsiella
      species isolated from children under five with intestinal & extraintestinal
      infections.
AB  - BACKGROUND & OBJECTIVES: Extended spectrum beta-lactamases (ES beta L) are
      enzymes produced in some Gram-negative bacilli that mediate resistance to third
      generation cephalosporins (3GC) and aztreonam. These are common in Klebsiella
      spp. and Escherichia coli and in other members of the family enterobacteriaceae.
      ES beta L production is accompanied by resistance to other antibiotics as these
      are encoded by multi drug resistance conjugative plasmids. The present study was
      undertaken to study the incidence of multi drug resistant and ES beta L producing
      Klebsiella spp. in children under five years of age suffering from intestinal and
      extraintestinal infections. METHODS: A total of 90 strains of Klebsiella spp. (76
      isolates of K. pneumoniae and 14 of K. oxytoca) were tested for resistance to 3GC
      antibiotics (ceftazidime, cefotaxime, ceftriaxone), amikacin, ampicillin,
      erythromycin, gentamycin and streptomycin by disc diffusion method. Isolates
      found resistant to 3GC antibiotics were tested for the production of ES beta L by
      double disc diffusion synergy test. Transconjugation experiments were done to
      study the transfer of drug resistance and ES beta L production from Klebsiella
      isolates to an Esch. coli strain (K12 J62-2). RESULTS: All the 90 isolates showed
      multi drug resistance; 87 (96.6%) isolates showed resistance or decreased
      susceptibility to at least one of the three 3GC. ES beta L production was
      detected in four strains of K. pneumoniae and two K. oxytoca. ES beta L activity
      could be experimentally transferred to recipient Esch. coli in all the 6
      isolates. Resistance to beta-lactam antibiotics was co-transferred along with
      resistance to gentamycin. INTERPRETATION & CONCLUSION: This study has shown the
      incidence of ES beta L producing Klebsiella strains in children in Chennai, and
      possibly poses a threat in the treatment and management of Klebsiella associated
      infections. The incidence of ES beta L producing strains of Klebsiella and other
      members of enterobacteriaceae should be carefully monitored in children to
      prevent unnecessary use of antibiotics especially 3GC and aminoglycoside
      antibiotics. Hence, tests for the detection of ES beta L producing Klebsiella
      strains should be carried out routinely for better therapeutic management.

PMID- 11968953
TI  - Investigation of malaria outbreak in Bahraich district, Uttar Pradesh.
AB  - BACKGROUND & OBJECTIVES: Based on the reports of 139 fever related deaths in
      Jarwal primary health centre (PHC) of Bahraich district, Uttar Pradesh (UP)
      during April to September 1999, a study was undertaken to explore the possibility
      of outbreak of Plasmodium falciparum malaria in the area and reasons of outbreak.
      METHODS: The study was undertaken during September-October 1999 in Bahraich
      district, UP. The study included a parasitological and an entomological survey.
      Blood slides from fever cases were collected and examined following standard
      procedures for detection of species and stage of parasite. The resting adult
      mosquitoes were collected from human dwellings and cattle sheds from selected
      villages. Susceptibility status of Anopheles culicifacies to 4 per cent DDT and
      0.05 per cent deltamethrin was determined under laboratory conditions following
      the WHO procedure. In vitro drug sensitivity of P. falciparum to chloroquine was
      also estimated. RESULTS: Overall slide positivity rate (SPR) was found to be 33.8
      with a preponderance of P. falciparum (88.4%). There was an outbreak of Pf
      malaria in Jarwal and surrounding areas as well. Foci of P. falciparum malaria
      were found in Jarwal, Fakharpur and Hazoorpur PHCs around Kaisarganj PHC. In
      addition, P. falciparum cases, were also reported from Motipur and Tejwapur.
      INTERPRETATION & CONCLUSION: Poor surveillance of affected areas resulting in low
      annual parasite incidence (API), lack of insecticidal spray in the currently
      affected PHCs as the API was less than 2 and development of resistance in P.
      falciparum to chloroquine were found as the possible reasons for the outbreak. It
      is recommended that surveillance be strengthened in all PHCs of Bahraich district
      to contain further extension of malaria in northeastern UP.

PMID- 11968954
TI  - Augmentation of non-specific immunity in mice by gold preparations used in
      traditional systems of medicine.
AB  - BACKGROUND & OBJECTIVES: Gold preparations are highly valued in Indian systems of
      medicine and extensively used for tonic and rejuvenating properties. This study
      was aimed to evaluate the effects of Ayurvedic gold preparation Swarna Bhasma
      (SB) and Unani preparation Kushta Tila Kalan (KTK) on non-specific immunity in
      mice. A gold-containing drug auranofin (AN) used in modern medicine was studied
      for comparison. METHODS: Male mice were administered with the incremental doses
      of these drugs orally for 10 days. Parameters of study included body weight,
      organ weight, peritoneal exudate cell (PEC) counts and phagocytic activity of
      PEC. RESULTS: Both test drugs (KTK and SB) significantly (P < 0.001) increased
      counts of peritoneal macrophages and stimulated phagocytic index of macrophages.
      AN elicited a suppressive action on these parameters. INTERPRETATION &
      CONCLUSION: Traditional preparations of gold exhibited immunostimulant activity
      on macrophage functions in contrast to immunosuppressive effects of AN. This is
      an interesting observation and gives a rational basis to the claims of efficacy
      and safety of gold when used in calcined forms.

PMID- 11968956
TI  - Nurses paying lip-service to asthma self-management.

PMID- 11968955
TI  - Measles epidemic in Ireland threatens mainland Britain.

PMID- 11968957
TI  - Breast drive lacks bottle.

PMID- 11968958
TI  - High risks for premature babies.

PMID- 11968959
TI  - Coronary heart disease.

PMID- 11968960
TI  - Should nursing stay self-regulated?

PMID- 11968961
TI  - Is NHS Direct the best thing to happen to nursing for years?

PMID- 11968962
TI  - Class consciousness.

PMID- 11968964
TI  - Mental health care is not a black and white issue.

PMID- 11968963
TI  - Dementia care must be realistic.

PMID- 11968965
TI  - Lives at risk--or votes?

PMID- 11968966
TI  - Intensive pressure.

PMID- 11968967
TI  - Critical mass.

PMID- 11968968
TI  - Invisible condom coming soon.

PMID- 11968969
TI  - Testing the pilots.

PMID- 11968970
TI  - Perfect 10. Nurses should be able to run their own clinics.

PMID- 11968971
TI  - Dignity on the ward: promoting excellence in care.

PMID- 11968972
TI  - A nurse-led clinic for lung cancer.

PMID- 11968973
TI  - Health visiting in a custodial environment.

PMID- 11968974
TI  - Preceptorship: making it happen.

PMID- 11968975
TI  - A practical guide to giving injections.

PMID- 11968976
TI  - Communicating with older people.

PMID- 11968977
TI  - Nurses: stressed, but committed.

PMID- 11968978
TI  - Drug administration. Risk over as government closes drug loophole.

PMID- 11968979
TI  - Taking care to the child.

PMID- 11968980
TI  - Midwives key to halting flood of cesareans.

PMID- 11968981
TI  - Dissecting child hearts 'leads to new cures'.

PMID- 11968982
TI  - Hospice care. Grim stereotype leaves terminally ill struggling.

PMID- 11968983
TI  - It's a new brand world: a CEO's guide to hospital branding and image management.

PMID- 11968984
TI  - Breaking down barriers. Information technology and rural health.
AB  - Fifty years ago, the number of beds was the only significant difference between
      rural and urban hospitals. Health care was a relatively "low tech" business.
      Hospitals in less-populated areas were able to provide the same services as their
      big-city counterparts. However, beginning in the 1960s, rapid advances in
      technology started to put rural hospitals at a disadvantage.

PMID- 11968985
TI  - Living up to your values.

PMID- 11968986
TI  - Leading by listening: a key to synergy.
AB  - Conflict abounds in health care. Some employees are disgruntled, feeling
      overworked and under-appreciated. Tensions between health care providers and
      payers are creating financial stresses. At times, physician and leader relations
      are strained. Government rules and regulations in the compliance arena have added
      to the malaise. The sources of conflict are seemingly endless.

PMID- 11968987
TI  - Caring for caregivers.
AB  - The need for managers to care for their employees has never been greater, because
      the need to retain good employees has never been greater. Pharmacists, nurse
      anesthetists, certified nurse aides, radiation oncology technicians, radiation
      technologists, and medical coders are in short supply in almost every part of the
      state, and more than 13 percent of nursing positions in the United States are
      open.

PMID- 11968988
TI  - Living the mission.
AB  - On Sept. 11, 2001, Saint Vincent Catholic Medical Centers (SVCMC) faced the
      truest measure of our community commitment. The overwhelming response of our
      staff toward the community, and of the community to our institution, left no
      question that our role as caregiver extends far beyond our walls and direct
      patient care.

PMID- 11968989
TI  - Getting your own personal trainer.

PMID- 11968990
TI  - Employee turnover: measuring the malady.
AB  - One measure of an organization's value to its employees is turnover. But how do
      you know if your employees are wondering if the grass is greener elsewhere? Scott
      Badler in his book What's So Funny about Looking for a Job? suggests a quick quiz
      to find out.

PMID- 11968991
TI  - Controlling information technology costs, Part 2.
AB  - Health care executives are increasingly frustrated by Information Technology
      (IT). Although our industry is often accused of underinvesting in technology
      (hospitals average 2-3 percent of their costs in IT, compared to other industry's
      8-10 percent), when IT investments are made, they fail to reflect demonstrable
      return to the bottom line. Yet the effective deployment of technology is so
      critical to the success of the organization and can in itself cause the failure
      of a health care system. While being forced to invest significant amounts of
      resources in the past two years preparing for Y2K, health care organizations have
      come under increasing financial pressures due to other industry developments.

PMID- 11968992
TI  - No time for training? No problem.
AB  - For the third part in the series of articles featuring innovative human resources
      programs in Michigan hospitals, the focus is on training staff. Hayes Green Beach
      Memorial Hospital, Charlotte, has implemented a program that ensures a new
      employee's compliance with training requirements and reduces the headaches that
      can come with fitting training into an already full work schedule.

PMID- 11968993
TI  - What is the accident waiting to happen?
AB  - Working on an MHA subcommittee has many benefits. The benefit I value the most is
      the opportunity to build relationships with people from hospitals across the
      state and share ideas that work. Recently, at an MHA patient safety committee
      meeting, I shared an initiative that Allan Franke, MD, from Partners Health Care
      System in Boston, presented at the Institute for Health Care Improvement in San
      Francisco.

PMID- 11968994
TI  - Value markers--the auto, boat, electronic and health care shows.

PMID- 11968995
TI  - Taking the public's pulse on health care.... Trust is at the heart of it all.

PMID- 11968996
TI  - Lessons learned.

PMID- 11968997
TI  - Retirees: untapped reservoir of talent.

PMID- 11968998
TI  - Medication error. Salty language.

PMID- 11969000
TI  - Infection control. Debugging equipment.

PMID- 11968999
TI  - Scope of practice. Stepping over the line.

PMID- 11969001
TI  - Applying antiembolism stockings.

PMID- 11969002
TI  - Anticoagulant assays. Erroneous results, unexpected source.

PMID- 11969003
TI  - Intrathecal midazolam. Preservative-free pain control.

PMID- 11969004
TI  - Timentin overdose. "No admittance" to the pharmacy?

PMID- 11969006
TI  - Slowing the spread of gonorrhea.

PMID- 11969005
TI  - Spotlight on nurse-anesthetists.

PMID- 11969007
TI  - Circumcision: is a local anesthetic appropriate?

PMID- 11969008
TI  - Rapamune. New tablet combats kidney rejection.

PMID- 11969009
TI  - Kineret. Easing the pain of rheumatoid arthritis.

PMID- 11969010
TI  - Serzone. Beware of dangerous liver problems.

PMID- 11969011
TI  - Labor and delivery. Dealing with a stillbirth.

PMID- 11969013
TI  - Forgiveness. Only human.

PMID- 11969014
TI  - Analgesia. Acupuncture makes a point of pain relief.

PMID- 11969012
TI  - Communication. Lighten our souls.

PMID- 11969015
TI  - Defibrillators. Close to the vest.

PMID- 11969016
TI  - Lyme disease. Disease incidence rising in the east.

PMID- 11969017
TI  - Getting a line on CVAD. Central vascular access devices.
AB  - Covering all types of central lines, these practical guidelines explain how you
      can protect your patients from complications--and protect yourself from
      malpractice accusations.

PMID- 11969019
TI  - How to perform 3- or 5-lead monitoring.

PMID- 11969018
TI  - Nursing 2002 salary survey.

PMID- 11969020
TI  - High blood pressure (hypertension).

PMID- 11969023
TI  - Practicing mediation.

PMID- 11969022
TI  - Code blue.

PMID- 11969021
TI  - New drugs 2002. Part II.

PMID- 11969024
TI  - Safety on the road. Tips for older drivers.

PMID- 11969025
TI  - Take care of yourself. Counsel for caregivers.

PMID- 11969026
TI  - Learning what hospice nurses know.

PMID- 11969027
TI  - EBCT: beaming in on coronary artery disease.

PMID- 11969028
TI  - Documenting a patient's confusion.

PMID- 11969029
TI  - Bleeding esophageal varices.

PMID- 11969030
TI  - [Gluteal abscess complicated by sepsis as the expression of Crohn's disease].
AB  - Two young women, aged 19 and 25 years, suffered from persistent perianal sepsis
      after local drainage of unusual gluteal abscesses. Preoperative CT scanning
      showed unrecognised and inadequately treated abscesses and signs of inflammatory
      bowel disease. Both patients underwent a reoperation: affected bowel segments
      were removed, stomas were created and abscesses were drained. In the case of
      unusual perianal abscesses the diagnosis 'Crohn's disease' must be considered.
      Preoperative examinations should include CT or MRI scans of the abdomen and
      pelvis. Intraoperative colonoscopy can often be helpful in assessing the extent
      of the affected bowel segment.

PMID- 11969031
TI  - [Evaluation of the Dutch Organ Donation Act: mostly disappointments].
AB  - In 1998, the Organ Donation Act became effective in the Netherlands. From the
      recent evaluation of this act, it appears that one of its important goals, the
      increase in organ donation, has not been achieved. The number of organ donations
      has decreased. Only one-third of the Dutch adult population has responded to the
      request to register in the Central Organ Donor Registry. All people aged 18 years
      and older are sent a form on which they can indicate whether or not they consent
      to donating their organs after death. When a non-registered person dies, the
      relatives will refuse organ donation in at least 75% of the cases. The most
      important means for improving this situation are the implementation of a presumed
      consent law, special attention to public education on the principle of
      reciprocity (quid pro quo), and an improvement of the procurement programs in the
      donor hospitals.

PMID- 11969032
TI  - [Postprandial glucose peaks in the pathogenesis of cardiovascular disease in
      diabetes mellitus; implications for metabolic control].
AB  - It has been shown both in type I and in type 2 diabetes that optimal glucose
      control retards the development of diabetes-related complications. The
      concentration of glycated haemoglobin (HbA1c) is a measure of metabolic control
      during the previous five weeks. Several studies have indicated that an elevated
      blood glucose level after an oral glucose tolerance test or after a meal (2-hour
      value: 7-11 mmol/l) is a better risk indicator for future cardiovascular disease
      and death than the level of fasting blood glucose or HbA1c. Increased glucose
      auto-oxidation, labile glycosylation and intracellular activation of the polyol
      pathway leading to increased oxidative stress are believed to play an important
      pathophysiological role. In addition, direct stimulatory effects of glucose on
      specific intracellular signalling peptides, such as protein kinase C, as well as
      a direct effect on the vessel walls also play a role. In future studies the
      challenge will be to demonstrate the specific effects of improved postprandial
      blood-glucose control, and to separate these out from the general effects of
      intensive therapy with oral medication and insulin on glucose control. People
      suffering from diabetes are best advised to direct their self control also at the
      bloodglucose level 1.5-2 h after a meal.

PMID- 11969033
TI  - [Asymptomatic bacteriuria; management choices in different patient groups].
AB  - Asymptomatic bacteriuria is a common medical condition, especially in women and
      elderly people. It is generally considered to be a benign condition, which does
      not require screening or antibiotic treatment. However, there are a few
      exceptions for which screening is possibly worthwhile. For children it is unclear
      whether the early detection of ASB can result in better clinical outcomes.
      Screening is therefore not advised, except for young children during the first
      few months after a symptomatic urinary tract infection. For pregnant women the
      use of screening for ASB is also unclear and in general not indicated. Research
      is necessary into the possible transition from ASB to pyelonephritis and the
      possible connection with low birth weight and premature births. There are
      indications that ASB in women with type I diabetes mellitus can lead to a
      deterioration in the renal function, yet these are insufficient to recommend
      screening as a routine procedure.

PMID- 11969034
TI  - [Diagnostic image (83). A girl with subfebrile temperature and ascites.
      Tuberculous peritonitis].
AB  - A subfebrile girl with ascites.--A 16-year-old Ethiopian girl who had been living
      in the Netherlands for 4 years had ascites and echogenic spots in the abdomen.
      Laparoscopy revealed peritonitis tuberculosa.

PMID- 11969035
TI  - [Endoscopic adrenal surgery: a new standard in 10 years].
AB  - OBJECTIVE: Description of the development of endoscopic adrenal surgery and the
      introduction of this procedure in Groningen University Hospital (GUH) and in the
      rest of the Netherlands. DESIGN: Literature overview, description of own results
      and results of a national survey. METHOD: Medline was searched with the search
      terms: 'laparoscopic', 'endoscopic' and 'adrenalectomy' for the period 1992-2001.
      During the period January 1998-July 2001, 39 patients underwent adrenal surgery
      at the GUH. A questionnaire about adrenal surgery was sent to 41 Dutch hospitals
      which provide surgical training. RESULTS: A total of 37 literature references
      were found, mostly prospective studies with a maximum of 130 patients, sometimes
      in retrospective comparison with conventional open surgery. No randomised studies
      were found. In the patient group at the GUH, 32 of the 39 patients had the
      adrenal gland removed endoscopically (82%). There were 3 (8%) primary open
      procedures due to tumour size (mean: 13 cm) and 4 (11%) conversions (mean tumour
      size: 6 cm). After 32 procedures, there was still a trend towards a shorter
      operation time. The response to the national survey was 88% (36/41). In 9% of the
      hospitals no adrenal surgery was performed. In the remaining hospitals minimally
      invasive adrenal surgery took place in about two-thirds of the patients, mainly
      via the retroperitoneal route (63%). More procedures were carried out in the
      university hospitals (mean: 11.6 per year) than in the non-university hospitals
      (mean: 2.9 per year). There were few concrete arrangements concerning the
      concentration of this technically demanding and rare procedure. CONCLUSION: Over
      the last 10 years endoscopic adrenalectomy has developed to become the new
      standard for the surgical removal of benign adrenal tumours with a diameter < 10
      cm. Although the procedure has an evident learning curve, there are still few
      concrete arrangements in the Netherlands concerning the necessary concentration
      of this difficult and rare technique.

PMID- 11969036
TI  - [Tetanus in a young unvaccinated girl after a fall in the street].
AB  - A 4-year-old girl developed tetanus after she had fallen on the street a week
      before. She had never been vaccinated and despite pressure from the family
      practitioner, the parents refused to allow her to be given human anti-tetanus
      immunoglobulin as a matter of principle after the wound had been stitched. Seven
      days later she was admitted to hospital with trismus and risus sardonicus. Upon
      initial treatment with human anti-tetanus immunoglobulin and penicillin, and
      subsequently metronidazole, her clinical condition deteriorated with opisthotonus
      and life-threatening respiratory insufficiency, upon which she was moved to the
      intensive-care department where she was intubated and mechanically ventilated for
      two weeks. Finally she made a complete clinical recovery. Thanks to the extensive
      national vaccination program, tetanus has become a rare disease in the
      Netherlands. However, the very serious course and possible fatal outcome warrant
      a keen attitude and adequate treatment.

PMID- 11969037
TI  - [A thyroglossal duct cyst with ectopic thyroid carcinoma].
AB  - An asymptomatic swelling in the neck of a 15-year-old boy, was revealed after
      resection to be due to a papillary thyroid carcinoma. He was treated with a near
      total thyroidectomy, radiotherapy at an ablation dosage due to a
      scintigraphically demonstrated remnant thyroid tissue, and thyroid hormone
      supplement. Almost 2 years after the tumour resection, a recurrent carcinoma was
      found in the neck. Prior to the resection of symptomatic thyroglossal duct cysts,
      it should be ascertained whether nodular thyroid abnormalities are present. In
      about 1% of resected thyroglossal duct cysts a carcinoma is found, most often of
      the papillary type. In 10-40% of the patients who undergo a subsequent
      thyroidectomy, malignant focuses are also found in the thyroid. In view of this
      multifocal occurrence and the fact that in most cases the diagnosis of carcinoma
      is only made after the operation, which often implies uncertainty about
      oncological radicalness, the authors advice to perform a (near-)total
      thyroidectomy as the standard procedure in case of thyroglossal duct carcinoma.
      After this adequate treatment with 131I should be given. A more limited approach
      seems only warranted when radicalness is certain and indications for nodular
      thyroid disease are absent.

PMID- 11969038
TI  - [Transfer of the care for adolescents with chronic illnesses: from pediatrics to
      specialists for adults].
AB  - Over the past few decades, paediatrics has increasingly been characterised by
      many developments in medical technology. This has led to a dramatic change in the
      clinical outcome of many severe and chronic childhood diseases. The number of
      children dying due to a severe illness has decreased, and at the same time the
      number of children surviving with a chronic disease or handicap has increased.
      This development requires that paediatricians and physicians in adult care adopt
      new initiatives so as to ensure an efficient and caring transfer of adolescents
      from paediatric to adult care. The purpose of this transition is (a) preparing
      the patient for the transfer to adult medicine by gaining an understanding of the
      clinical picture and the treatment goal and possibilities, and obtaining a
      personal responsibility for medication and diet and (b) tuning paediatric care
      and adult care to one another. Procedures for the transition should be
      established in a protocol. The responsibility for monitoring the process lies in
      principle with the treating paediatrician.

PMID- 11969039
TI  - [Significance of medical data in work disability evaluation].

PMID- 11969040
TI  - [Significance of medical data in work disability evaluation].

PMID- 11969041
TI  - [Surgical gauze left behind].

PMID- 11969042
TI  - [Significance of medical data in work disability evaluation].

PMID- 11969043
TI  - Retroperitoneal ancient schwannoma: case report and analysis of clinico
      radiological findings.
AB  - Ancient schwannoma is a rare subtype of typical schwannoma, with histological
      predominance of degenerative findings. We report the second case of
      retroperitoneal ancient schwannoma (occurred in a 45-year-old female referred to
      our institution for an unremitting right lumbar pain) and pinpoint clinical,
      radiological, prognosis and therapeutic aspects of this tumor.

PMID- 11969044
TI  - [Ureteral lithiasis, what treatment?].
AB  - Extracorporeal shock wave lithotripsy and ureteroscopy are minimal invasive
      techniques, both of which have definitively become essential for the treatment of
      ureteral stones resistant to conservative treatment. At the time of evidence
      based medicine, no study makes it possible to recommend one of these methods
      rather than the other. For stones of identical size and location, this review of
      the literature shows that extracorporeal shock wave lithotripsy and ureteroscopy
      prove of comparable effectiveness and innocuousness. The urologist thus has two
      alternatives of which the technical control, the availability of the endoscopes
      or lithotriptors as well as the desire and comfort of the patients are the
      factors which condition his choice of the method for the treatment of ureteral
      stones.

PMID- 11969045
TI  - [Endoscopic treatment of vesico-ureteral reflux by submeatic injection of
      autologous fat. Two case reports].
AB  - The authors report two cases of endoscopic treatment of vesico-ureteral reflux by
      submeatic injection of autologous fat. We describe the technique of prelevement
      and injection. The immediate results confirm the efficacity of this procedure.
      The long-term follow-up will allow us to adopt it and to give it some
      modifications.

PMID- 11969046
TI  - [Classification, favorable characteristics, prevention and treatment of adverse
      side-effects associated with Bacillus Calmette-Guerin in the treatment of
      superficial bladder cancer].
AB  - The efficacy of Bacillus Calmette-Guerin (BCG) in the treatment of superficial
      bladder cancer was first reported by Morales in 1976. Several authors have since
      demonstrated the efficacy of BCG in the prophylaxis and treatment of high-risk
      superficial bladder tumors (pT1G3, CIS). Although BCG is now recommended as an
      adjunctive treatment for superficial bladder tumors, the optimal treatment
      schedule remains to be defined. Results reported by Lamm suggest that an initial
      induction cycle of six weekly intravesical BCG instillations is suboptimal unless
      maintenance therapy (three consecutive weekly instillations) is given 3, 6, 12,
      18, 24, 30 and 36 months later. However, the use of maintenance therapy is
      hindered by troublesome adverse reactions. This article reviews adverse reactions
      associated with BCG treatment, proposed a classification and discusses their
      prevention and treatment.

PMID- 11969047
TI  - [Detrusor-sphincter dyssynergia: four case reports and literature review].
AB  - Detrusor-sphincter dyssynergia is responsible for major impairment and is factor
      for social and professional activity repercussions. METHODS: We have studied the
      clinical and urodynamic finding in four patients (two men and two women) with
      detrusor-sphincter dyssynergia. Mean age is 36 years (26-44 years). Dyssynergia
      was secondary to tuberculosis meningitis in one case, surgery for rectal
      adenocarcinoma in one case, tight vertebral canal in one case and in one case the
      cause is indeterminate. The detrusor-sphincter dyssynergia were treated by
      autocatheterism in two cases, antibiotherapy antituberculosis associated with an
      anticholinergic drugs in one case and by alpha-blockers agent in another.
      RESULTS: Quasi-complete salvage of the motor deficit and the dysfonctional
      voiding in a patient treated by antibiotherapy antituberculosis associated with
      an anticholinergic drugs. As well, maid evolution in patient treated by alpha
      blockers agent and who practice self catheterization. CONCLUSION: Optimal
      treatment is unknown, and the existence of several cures indicated the limit of
      all therapeutic methods.

PMID- 11969048
TI  - [Inflammatory pseudo-tumor of the urachus: a case report].
AB  - One case of inflammatory pseudo-tumor revealed by mictional disorders is
      reported. Ultrasonography and computed tomography visualised a non specific
      formation of bladder dome witch extend to the Retzius space and umbilicus. The
      diagnosis of urachal tumor had been suspected. Anatomopathologic analysis of the
      operative piece disclose a diagnosis of the urachal remnants with foreign body
      type of inflammation. Since malignant transformation of urachal remnants is
      possible, surgical resection is advised.

PMID- 11969049
TI  - [Retrovesical pseudocyst : difficult diagnosis of one case and literature
      review].
AB  - Retrovesical localization of a cystic mass is rare. The authors report one
      observation of hematic retrovesical pseudocystic formation having a difficult
      diagnosis. In the light of this observation, different diagnostic patterns of
      cystic and pseudocystic retrovesical formation are discussed.

PMID- 11969050
TI  - [Anterior urethral duplication in a male child. A case report].
AB  - Urethra duplication is a rare anomaly with numerous anatomic variations. These
      fall into four main groups: epispadiac, hypospadiac, fusiform, and Y-type. We
      report on one case of sagittal incomplete hypospadiac anterior duplication of the
      urethra. Surgical repair consisted of incision of the septum between the two
      urethras and hypospadias repair at the same setting. Follow-up was characterized
      by the occurrence of some complications.

PMID- 11969052
TI  - [Multiple leiomyoma of the scrotum. A case report].
AB  - A variety of neoplasms derived from mesechymal elements may arise on the tunica
      dartos, the tunica albuginea or, more rarely, within the testis or the
      epididymis. The authors report a case of leiomyoma of the scrotum in a 33-year
      old man. This rare and benign tumour is localized in the tunica dartos in 8% of
      cases. The positive diagnosis is based on histological examination after
      conservative treatment by local excision which gives excellent results.

PMID- 11969051
TI  - [Anterior urethral injury. Report of 23 cases].
AB  - We reviewed our experience in managing anterior urethral traumatic rupture.
      PATIENTS AND METHODS: Between January 1986 and December 1998 a total of 23
      consecutive male patients with anterior urethral trauma were studied
      prospectively, including a clinical and radiographic of the pelvis examination,
      excretory urography and retrograde urethrography. The average patient age was 29
      years (range 19 and 65 years). The mechanism of injury was represented by the
      blunt perineal trauma in 17 cases and the cavernous body rupture in six cases.
      Clinical manifestations are dominated by the urethrorragia (19 cases), urinary
      retention (16 cases), perineal hematoma (14 cases). Radiological imaging have
      shown a pelvic fracture (six cases), urethral rupture (17 cases) and bladder
      rupture (three cases). Therapeutic procedure realized in emergency in six
      patients having a cavernous body lesion and delayed repair in 17 other patients.
      RESULT: The outcame was favorable in 12 patients and recurrence stenosis has
      occurred in 11 patients who are corrected by optical urethrotomy (four cases),
      end-to-end anastomosis (two cases), B. Johanson urethroplasty (three cases)
      urethroplasty by penile skin (one case), dilations (one case). CONCLUSION:
      Suprapubic cystostomy with healing control of the partial ruptures, delayed end
      to-end anastomosis for total ruptures and immediate reparation of the urethral
      rupture when associated with a penile fracture are even the best warrant of a
      correct functional recovery.

PMID- 11969053
TI  - [Kidney cancer in horseshoe kidney. A case report of an unexpected diagnosis].
AB  - The authors report a case of renal cell carcinoma in a horseshoe kidney and
      discuss diagnostic and therapeutical aspects arising from this combination. Renal
      carcinoid tumors and nephroblastoma seems to be more frequent in this
      malformation. Diagnosis of horseshoe kidney may be difficult and angiography
      examination is very useful to confirm renal anomaly, tumor situation, and to plan
      the surgical approach because vascularization vary case to case. Heminephrectomy
      adapted to neoplasic localisation remains the essential treatment.

PMID- 11969054
TI  - [Pheochromocytoma in children. Two case reports].
AB  - Severe sustained hypertension occurs in only 0.1% of the pediatric population and
      only about 2% of these patients will have an underlying endocrine cause.
      Pheochromocytoma as a catecholamine secreting tumour causing severe hypertension
      is exceedingly rare in children. A high index of suspicion and an awareness of
      the clinical spectrum are therefore necessary to make the diagnosis. We report
      two cases of pheochromocytoma occurring in two a 12 year-old boys who's presented
      with sustained hypertension, headache, sweating, and visual blurring. Measurement
      of 24 hour urinary catecholamines showed a marked increase and localization of
      adrenal unilateral pheochromocytoma was determined by ultrasonography and
      computed tomography. The approaches to the adrenal gland were transverse
      transperitoneal and the excision of the tumors was followed of return to the
      normal of tensional numbers.

PMID- 11969055
TI  - Adrenal myelolipoma. A case report.
AB  - We report a new case in a 56 years old patient who manifested right side's pains.
      The abdominal CT scan showed a tumor of the right adrenal gland with fat density
      (size: 8 x 6 x 6 cm). This tumor was removed surgically (weight: 300 g). The
      histological finding revealed a proliferation of adipocyts and myeloid tissue
      which contains megakaryocytes, erythroid cells and lymphocyts. The outcome is
      good after three years of surgery. The surgical treatment becomes necessary when
      the tumor's size increases or it becomes symptomatic.

PMID- 11969056
TI  - [Hydatid cyst of the adrenal gland. A case report].
AB  - The hydatid cyst of the adrenal gland is still an exceptional localization. Only
      eleven cases have been described in the literature. A new case of isolate
      suprarenal hydatidosis is reported in one 28 years old patient, that the signs
      consisted in pains of the right flank and vomiting. The diagnosis has been based
      on the imagery, particularly the computed tomography associated to the hydatid
      serology, confirmed during the operation and by the pathologic examination of the
      resected piece. The treatment consisted in a simple cystectomy with conservancy
      of the gland, the operative sequelae have been simple. The interest of this cases
      lies in the rare feature of this hydatid localization that the diagnosis is
      difficult. Among the various suggested surgical methods, the simple resection of
      the cyst is still the best treatment that permits to keep the gland.

PMID- 11969057
TI  - Why give a child growth hormone?
AB  - Short stature is one of the commonest chronic problems encountered in paediatric
      practice, possibly because almost any long-term disease in children can slow
      growth and because parents may regard short stature as a disability in itself.
      For some, a potential treatment is growth hormone and, in England alone in 2000,
      over 39,000 prescriptions, costing more than 26.8 million Pounds, were dispensed
      for synthetic human growth hormone (somatropin), mostly for children. Here, we
      discuss the place of synthetic human growth hormone in the management of children
      with short stature associated with growth hormone deficiency or other conditions,
      such as Turner's syndrome and chronic renal insufficiency.

PMID- 11969058
TI  - Frameless intra-uterine contraceptive device (GyneFix).
AB  - Modern copper-containing contraceptive intra-uterine devices (IUDs) typically
      comprise a solid plastic frame loaded with copper wire and/or copper sleeves.
      Although they are very effective (annual pregnancy rates generally below 1%),
      some women discontinue their use within a year after insertion because of
      excessive bleeding and/or painful periods (4-15%), or because the device has been
      spontaneously expelled (2-8%). GyneFix (Contrel) is a new IUD approved for up to
      5 years of use. Its manufacturer claims that the device produces fewer unwanted
      effects, and is less likely to be expelled, than conventional IUDs because it
      does not have a plastic frame (a frameless device). Here we assess these claims.

PMID- 11969059
TI  - Should H. pylori be eradicated in non-ulcer dyspepsia?
AB  - Around half of patients with dyspepsia have no abnormal findings on endoscopy
      ('non-ulcer dyspepsia') yet, of these, 55% have Helicobacter pylori infection of
      the gastric mucosa. The eradication of H. pylori infection cures most patients
      with duodenal and gastric ulcer. Here, we discuss whether H. pylori eradication
      cures patients with non-ulcer dyspepsia.

PMID- 11969060
TI  - Living related kidney transplantation in a 15-year-old patient with type I
      hyperoxaluria: a case report.
AB  - The following is a case report of a patient with type I hyperoxaluria who
      received a living related renal transplant for end-stage renal disease. The
      deficiency or complete absence of the hepatic enzyme alanine glyoxalate
      aminotransferase characterizes type I hyperoxaluria. When deficient, an
      overproduction of oxalate occurs, which then can be deposited in multiple end
      organ systems. When performing surgery on a patient with type I hyperoxaluria,
      the anesthetist needs to be aware that these patients can have a host of problems
      ranging from cardiovascular anomalies to end-stage renal disease. A careful
      assessment of each system needs to be performed, along with vigilant planning of
      the anesthetic regimen. Through proper planning and implementation, a safe and
      effective anesthetic usually can be performed.

PMID- 11969061
TI  - Meta-analysis of the effectiveness of nonsteroidal anti-inflammatory drugs in a
      standardized pain model.
AB  - A comprehensive meta-analysis using strict inclusion criteria examined 8 studies
      comparing the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and
      codeine-based oral analgesics for treating moderate to severe oral surgery pain.
      The studies involved 1,163 patients, drawn from a literature search of more than
      300 studies published since 1990. Of the 8, 5 showed significantly better
      outcomes (P < .05) with NSAIDs, while 3 showed no differences in outcomes (P >
      .05). Adverse reactions were greater in the opiate group (P < .001). Data from
      the 8 studies were subjected to standardized data transformation and analysis
      procedures using preselected pain measurement inventories. An oral surgery pain
      model was used because it is relatively free of confounding variables, thereby
      leading to clearer results. Results of the meta-analysis revealed that NSAIDs
      were either as effective or more effective than codeine-based analgesics for
      treating the moderate to severe pain associated with oral surgery. NSAIDs also
      were associated with fewer complications. Based on this analysis, NSAIDs should
      be considered for the control of postoperative oral surgery pain.
      Generalizability to other forms of postoperative pain remains speculative.

PMID- 11969062
TI  - A follow-up survey of the use of complementary and alternative medicines by
      surgical patients.
AB  - This study investigated the use of complementary and alternative medicines by
      surgical patients at the University of Colorado Health Sciences Center, Denver.
      Elective surgical outpatients were randomly surveyed with anonymous self-report
      questionnaires during day-surgery admission about alternative medicines taken
      during the 2 weeks before surgery; 496 of 500 questionnaires were completed and
      returned. Of the patients, 37% reported 62 types of herbs, 59% reported 14 types
      of vitamins, 45% reported 36 types of of dietary supplements, and 1% reported
      taking 5 types of homeopathics. A total of 73.4% of patients took alternative
      medicines preoperatively (range, 1-44 medicines). After a literature review, the
      alternative medicines were categorized for potential interactions with anesthetic
      drugs. Alternative medicines that have inhibitory effects on the coagulation
      cascade were reported by 40% of surgical patients. The following percentages of
      patients took medicines that affect blood pressure, 32%; affect cardiac function,
      20%; cause sedation, 17%; or have potential to alter electrolyte levels, 9%.
      Herbs recognized to interact with pharmaceuticals were consumed by 23% of
      patients. Further research, education, and improved communication are needed to
      safely integrate alternative medicines for surgical patients.

PMID- 11969063
TI  - Use of the Bullard laryngoscope in the adult patient with epiglottitis: a case
      report.
AB  - This case report involves the anesthetic management of a rare case of adult
      epiglottitis. It is unique in that there are real photographs of the illness and
      a previously undocumented use of a specific airway adjunct in acute epiglottitis,
      the Bullard laryngoscope. Management of the case from start to finish is
      discussed, as well as the usefulness of the Bullard laryngoscope in a difficult
      intubation scenario.

PMID- 11969064
TI  - Perioperative considerations in major orthopedic trauma: pelvic and long bone
      fractures.
AB  - Although pelvic fractures constitute a small percentage of total orthopedic
      injuries, they are associated with highest mortality rate. Pelvic fractures,
      along with long bone fractures, frequently are the result of significant blunt
      trauma often encountered in high-speed motor vehicle accidents. However, other
      types of trauma can cause these devastating injuries. Early recognition and a
      high index of suspicion are necessary to ensure that effective and aggressive
      resuscitation is instituted immediately. Expeditious assessment in the emergency
      department and care of the patient with pelvic and long bone fractures will
      greatly enhance the ongoing resuscitation in the operating room. Potentially life
      threatening associated injuries in these patients make resuscitation even more
      challenging. Therefore, a basic knowledge of the mechanisms of injury, early
      treatment in the emergency department, and the factors that affect intraoperative
      management will help optimize the outcome for patients with these injuries. This
      course describes the perioperative concerns and the evaluation and treatment of a
      patient with a pelvic or a long bone fracture.

PMID- 11969065
TI  - AANA Journal Course: Update for Nurse Anesthetists--Thermoregulation: anesthetic
      and perioperative concerns.

PMID- 11969066
TI  - The difficulties of complying with TEFRA.

PMID- 11969067
TI  - The AANA Foundation closed malpractice claims study: obstetric anesthesia.
AB  - The purpose of this study was to evaluate the anesthesia care provided during
      obstetric adverse events. Malpractice claims filed against nurse anesthetists for
      care involving obstetric anesthesia (n = 41) were extracted from the American
      Association of Nurse Anesthetists Foundation Closed Claim database. The events
      represented in the claims occurred from 1990 to 1996 and represented anesthetics
      provided by both anesthetists and anesthesiologists. Risk factors for adverse
      outcomes identified in this study included advanced maternal age, ethnicity, and
      obesity. Patients requiring emergency cesarean sections under general anesthesia
      were found to be at considerable risk for sentinel events. The most common
      adverse outcome in the obstetric closed claim database was neonatal death (n = 11
      [27%]), followed by maternal death (n = 9 [22%]) and complications resulting from
      regional anesthesia (n = 8 [20%]). The leading cause of maternal death and brain
      damage was a failure to secure a patient airway. The mode of delivery in 95% (n =
      19) of the 20 claims in which death was the outcome was surgical. In the claims
      representing maternal death, 89% (8) of the 9 claims represented surgical
      deliveries under general anesthesia. These maternal death cases were designated
      emergent in 56% (5) of the claims. The anesthetic care was deemed appropriate in
      56% (23) of the claims. The median payment for appropriate care ($2,866.00) was
      less than for care determined to be inappropriate ($45,000.00).

PMID- 11969068
TI  - [A study of factors affecting the efficiency of electrofusion of enucleated eggs
      and cell-donors of nuclei].
AB  - We studied the capacity of rabbit oocytes for electrofusion with morula
      blastomeres and fetal fibroblasts. The morula blastomeres fused with aging
      ooplasts more readily than the fetal fibroblasts: 92.9 versus 63.0%, p < 0.001.
      The fetal fibroblasts fused with young enucleated oocytes more efficiently than
      with the aging ones: 98.4 versus 63.0%, p < 0.001. Serum starvation of the fetal
      fibroblasts in DMEM medium for 7-14 days reduced their capacity for fusion with
      young ooplasts, as compared to that after starvation for 0-4 days: 67.2 versus
      98.9%, p < 0.01). The increased time of "starvation" in an "impoverished" medium
      reduced the capacity of fetal fibroblasts with aging ooplasts as compared to the
      fibroblasts cultivated in the full medium and in the "impoverished" medium for
      one or two days: 64.5 versus 37.4%, p < 0.01. Hence, the efficiency of the fusion
      of the oocytes with nuclear donor cells depends on the age of the recipient
      oocyte, the origin of nuclear donor cells, and the conditions of cultivation.

PMID- 11969069
TI  - [In vitro development of murine embryos using different types of
      microinjections].
AB  - We studied the effects of different types of microinjections, such as the
      mechanical damage to cytoplasmic and nuclear membranes of the zygote and the
      injection of various gene-engineering constructs or buffer solutions into the
      cytoplasm or the pronucleus, on the preimplantation of murine embryos (CBA x x
      C57BL)F1. The survival rate of the embryos was estimated by their capacity to
      develop in vitro to the blastocyst or hatched blastocyst stages. Puncture of the
      cytoplasm using a microneedle and injection of buff or foreign DNA did not affect
      the zygotes capacity for further in vitro development. But, the puncture of the
      pronucleus and microinjection of gene-engineering constructs or buffer into it
      reliably decreased the survival rate of embryos, as compared to the control. The
      differences were found in the capacity of murine zygotes for in vitro development
      after injection with gene-engineering constructs.

PMID- 11969070
TI  - [Changes in the relative number of bipolar-like cells in the retina of
      Pleurodeles waltl as a function of age and as a result of light exposure].
AB  - The study of the population of bipolar-like cells (displaced bipolars) was
      continued in order to establish their role in development and regeneration of the
      retina in lower vertebrates. The size of the population of these cells was
      estimated on serial semithin sections in the retina of normal eyes in adult and
      young newt Pleurodeles waltl, as well as in adult newts subjected to long-term
      bright illumination. The population of displaced bipolars was significantly
      increased with reference to all cells of the outer nuclear layer. In young and
      illuminated animals, their numbers were approximately 1.3 and 1.4 times that in
      the adult animals not exposed to constant light. The results obtained favor the
      earlier suggestion of the involvement of the displaced bipolars in growth and
      restoration of the outer nuclear layer in the retina of newts during development
      and after trauma.

PMID- 11969071
TI  - [Development of the gill system in early ontogenesis of Danio and nine spike
      stickleback].
AB  - We studied specific features of development of the gill system during ontogenesis
      of the zebrafish Danio rerio and ninespine stickleback Pungitius pungitius, which
      differ in the rates of gill system, development. Although the development of
      sticklebacks proceeds in nature at lower temperatures than for zebrafish, the
      rate of gill formation in the former is higher. These differences are related to
      the specific conditions in which these fish develop: embryonic and larval
      development of the stickleback proceeds in bodies of water with a lower oxygen
      content than for zebrafish, and this results in the adaptive alteration of the
      rate of gill system development. Differentiation of gills in the zebrafish is
      accompanied by a manifold increase in the oxygen consumption rate. At different
      developmental stages, the incremental rates of oxygen consumption and increase in
      the body mass of the zebrafish larvae and fry differed significantly.

PMID- 11969072
TI  - [Hypothalamo-pituitary system controls the development of humoral immune response
      during prenatal ontogenesis in rats].
AB  - We studied the influence of the neuroendocrine system on the development of
      humoral immune response to sheep erythrocytes in rat fetuses. The removal of
      brain in utero by decapitation of 18-day fetuses induced a fourfold increase in
      the number of antibody-forming cells in the liver, as compared to the unoperated
      fetuses. After the removal of the forebrain, including hypothalamus
      (encephalectomy), the number of antibody-forming cells was comparable to that in
      unoperated fetuses. The observed increase in the number of antibody-forming cells
      in the liver was not due to a disturbed migration of precursors of B-lymphocytes
      in the spleen, since their content in the spleen was also four times that in the
      encephalectomized and unoperated fetuses. The increased number of antibody
      forming cells in decapitated fetuses could be due to an enhanced proliferative
      activity of the lymphocytes in the liver of these fetuses. It has been proposed
      that humoral immunity is controlled by the hypothalamo-pituitary-adrenal system
      already during prenatal development; the adrenocorticotropic hormone and
      glucocorticoids appear to be involved in this regulation.

PMID- 11969073
TI  - [Vascularization and development of the cytoarchitecture in the human neocortical
      rudiment].
AB  - The development of cytoarchitectonics of the brain rudiments in mammals is
      accompanied by the formation of an intracerebral vascular network. The
      relationship between these two processes is insufficiently clear. We studied the
      development of blood vessels and cytoarchitectonics in the neocortical rudiment
      of 6- to 13-week old human embryos. The light and electron microscopy methods
      were used, as well as histochemical visualization of NADPH-diaphorase in the
      vessel cells. The endothelium proliferation was evaluated using antibodies to
      proliferating cell nuclear antigen. Starting from week 8 of development, the
      tangentially oriented vessels formed a intraneural network in the ventricular
      zone of the rudiment, which appears to restrict the motility of neuroepithelial
      cells. The basal membrane was initially absent, and the neuroepithelial cells
      were in direct contact with the endothelial cells. During week 9 of development,
      the tangentially oriented vessels appeared in the intermediate zone. Formations
      similar to glial legs with short regions of the basal membrane adjoined the walls
      of inter- and intraneural vessels (note that, according to the published data,
      glial fibrillary acidic protein is not yet visualized at this stage).
      Angioarchitectonics depended little on the cell population density in different
      zones of the rudiment; specifically, the cortical plate did not contain
      tangentially oriented vessels until week 12-13 of development. The data we
      obtained suggest that the blood vessels fulfill a special morphogenetic function
      in the developing neocortex.

PMID- 11969074
TI  - [Dormant stages of the green flagellate Volvox in a natural habitat].
AB  - Reproduction and formation of resistant dormant spores in Volvox aureus (Ehr.)
      and V. tertius (Meyer) were studied in a biocoenosis of a transient pool in July
      August 1996 and 1997. Under these conditions, the populations of two Volvox
      species had species-specific reproductive features. In the V. tertius population,
      a relatively small amount of male individuals and dormant spores (zygospores)
      appeared sporadically. On the contrary, in the V. aureus population, dormant
      parthenospores were formed, but male individuals were never observed.

PMID- 11969075
TI  - [Investigation of the effect of various buffer solutions used for microinjection
      of gene-engineering constructs on preimplantation development of mouse embryos].
AB  - We studied the effects of some buffer solutions used for microinjection in
      mammalian zygotes on preimplantation development of (CBA x C57BL)F1 mouse embryos
      in vitro. The rate of embryo survival was estimated according to their capacity
      to develop to the stages of blastocyst and blastocyst hatched from zona
      pellucida. The results obtained suggested a reduced rate of survival of zygotes
      to the blastocyst stage after the injection into a pronucleus of the buffers Tris
      HCl with EDTA, Tris-HCl with MgCl2 and NaCl, and medium M2 (p < 0.05) and to the
      stage of blastocyst hatched from zone pellucida after injection of a Dulbecco
      solution, as compared to the control. No differences were found in the survival
      rate of zygotes injected with different buffer solutions.

PMID- 11969076
TI  - [N.K. Kol'tsov's theory of synthetic biology].
AB  - The state of theoretical biology in the twentieth century is characterized, as
      well as the appearance and development of N.K. Kol'tsov's scientific program, his
      original methodology of interdisciplinary synthesis, and, based on it, the
      concept of theoretical biology.

PMID- 11969077
TI  - [Changes in chromatin organization during early development and carcinogenesis].
AB  - Similar changes in chromatin organization take place during development and
      carcinogenesis. The size of chromatin loop domains fixed on the nuclear skeleton
      (matrix) increased from 20 to approximately 200 kbp. These changes are
      accompanied by an increased size of replicons and altered specificity of loop
      attachment to the nuclear matrix. During carcinogenesis, inverse changes in the
      chromatin structure are observed, neoplastic cells are dedifferentiated and
      return to the initial state. In this review, we consider new experimental data on
      organization of the DFNA loops and nuclear matrix in embryogenesis and
      carcinogenesis.

PMID- 11969078
TI  - [Characteristics of the cells producing thymic chemotactic factor for bone marrow
      stem cells].
AB  - It was shown using complement-dependent cytolysis and monoclonal antibodies
      against CD4, CD8, and NK1.1 antigens that the cortisone-resistant CD3+4-8-NK1.1(
      )-thymocytes spontaneously secreted a chemotactic transmitter inducing the
      release and directed migration of bone marrow cells. When estimating the general
      profile of the cytokines of these thymocytes by PCR with revertase, it was
      demonstrated the cells in question did not express cytokines with colony
      stimulating activities (SCF, IL-3, or GM-CSF) or cytokines affecting the
      migration of bone marrow stem elements (IL-2, 4, or 7). In addition, an active
      expression of gene bcl-2 was detected. Thus, the chemotactic cytokine inducing
      the release of bone marrow stem elements is a product of the cortisone-resistant
      long-living CD3+4-8-NK1.1(-)-T-cells of the thymus.

PMID- 11969079
TI  - [A study of expression of cell cycle genes in Drosophila using an enhancer trap
      and radioautography].
AB  - The phase of expression of genes CycB, CycE, and chb were determined in the cell
      cycle of neuroblasts of D. melanogaster 3rd instar larvae using the previously
      described radioautographic method and software. CycB was expressed at G2 phase
      and upon transition from G2 phase to M phase, while CycE was expressed at the end
      of G1 phase and upon transition from G1 phase to S phase. The phase of expression
      of the centrosome-associated protein was determined more precisely in G2 phase.
      The mean life span of reporter beta-galactosidase in neuroblasts was 4 h. The
      existence of more than one peak of expression of the gene in question in the cell
      cycle is discussed.

PMID- 11969080
TI  - [In honor of R.B. Khesin (1922-1985)].

PMID- 11969082
TI  - [RNA polymerase as a molecular machine].
AB  - Structure and function of DNA-dependent RNA polymerase is considered in terms of
      a conveying molecular machine. The use of mechanical energy and mechanical
      devices, such as "power-stroke motor", is supposed unlikely in the conveying
      function of RNA polymerase, as well as other molecular machines. Brownian motion
      and thermal mobility of macromolecules and their parts are postulated as the only
      motive impulse at the molecular level. Binding of substrates and subsequent
      chemical reaction as the energy input may provide successive selection and
      fixation of alternative conformational states of the enzyme complex thus
      providing the directionality of the conveyance ("Brownian ratchet mechanism").
      The following sequence of events "substrate binding--fixation of a certain
      conformational state--chemical reaction--fixation of an alternative
      conformational state--translocation (dissociation and downstream reassociation)
      of product-template duplex" is proposed as the principal scheme of the forward
      movement of RNA polymerase along DNA template.

PMID- 11969081
TI  - [The RNA polymerase structure-activity studies (1962-2001)].
AB  - The study of RNA polymerase initiated by R.B. Khesin is conducted for about forty
      years at the laboratory founded by him (since 1989, in collaboration with A.
      Goldfarb's laboratory). Genetic methods are used in combination with methods of
      the specific chemical crosslinks of nucleic acids with proteins. The paper
      assesses the main results of the study in comparison with the X-ray
      crystallographic data of high resolution obtained recently. A short comparative
      summary of the RNA polymerase structure has been done for bacteria,
      archaebacteria, and eukaryotic organelles and nuclei. A brief history of the RNA
      polymerase study is also presented.

PMID- 11969083
TI  - [Horizontal transfer of mercury resistance genes in natural bacterial
      populations].
AB  - The results of studying the horizontal transfer of mercury resistance
      determinants in environmental bacterial populations are reviewed. Identical or
      highly homologous mercury resistance (mer) operons and transposons were found in
      bacteria of different taxonomic groups from geographically distant regions.
      Recombinant mer operons and transposons were revealed. The data suggest high
      frequencies of horizontal transfer and of recombination for mercury resistance
      determinants. The mechanisms of horizontal gene transfer were elucidated in Gram
      negative and Gram-positive bacteria. New transposons were found and analyzed.

PMID- 11969084
TI  - [Bacterial genomic islands: organization, function, and role in evolution].
AB  - Data on the structural organization and evolutionary role of specific bacterial
      DNA regions known as genomic islands are reviewed. Emphasis is placed on the most
      extensively studied genomic islands, pathogenicity islands (PAIs), which are
      present in the chromosome of Gram-negative and Gram-positive pathogenic bacteria
      and absent from related nonpathogenic strains. PAIs are extended DNA regions that
      harbor virulence genes and often differ in GC content from the remainder of the
      bacterial genome. Many PAI occur in the tRNA genes, which provide a convenient
      target for foreign gene insertion. Some PAI are highly homologous to each other
      and contain sequences similar to ISs, phage att sites, and plasmid ori sites,
      along with functional or defective integrase and transposase genes, suggesting
      horizontal transfer of PAI among bacteria.

PMID- 11969085
TI  - [Role of double-stranded RNA in eukaryotic gene silencing].
AB  - Data on RNA interference, that is, posttranscriptional gene silencing by
      homologous double-stranded (ds) RNA, are reviewed. Gene silencing caused by
      exogenous dsRNA in artificial systems and observed in transgenic organisms
      carrying additional gene copies is considered. Data are summarized on the
      mechanism that arose during evolution of the Drosophila melanogaster genome to
      suppress repetitive genes with the use of dsRNA and thereby to prevent male
      sterility. The role of dsRNA in inhibiting expression and transposition of mobile
      elements is discussed on the basis of authors own and published findings.

PMID- 11969086
TI  - [Chromatin structure, heterochromatin, and transposable genetic elements--are
      they from one team?].
AB  - Gene content proved to be less than expected in completely sequenced eukaryotic
      genomes. Moreover, gene number differs only three times between such distant
      organisms as human and Drosophila. Hence it is likely that the essential
      functional and structural differences between the two species mostly depend on
      the regulation of gene activity than on the set and quality of genes themselves.
      New data demonstrate that changes in chromatin structure play a greater role in
      the fine gene activity regulation than considered before. R.B. Khesin had foresaw
      many chromatin functions that only recently came to be recognized. Khesin was
      interested in genome inconstancy over his last years. A higher content of several
      important chromosomal proteins was recently revealed in chromatin of transposable
      genetic elements (TGE). The possible role of TGE in chromatin organization in the
      nucleus is considered.

PMID- 11969087
TI  - [Mobile gene cassettes and DNA integration elements ].
AB  - Integrons are unique natural systems for capturing and spreading the antibiotic
      resistance genes among Gram-negative bacteria. Gene transfer into small genomes
      and into plasmids is via site-specific recombination. Integrons act as receptors
      of antibiotic resistance cassettes. There are known more than 50 cassettes
      conferring resistance to beta-lactams, aminoglycosides, trimethoprim,
      chloramphenicol, streptomycin, and other antibiotics. The structure of integrons
      and of gene cassettes are described and the mechanisms of capture, mobilization,
      and expression of cassettes considered.

PMID- 11969088
TI  - [A possible role of genetic translation ambiguity in evolution ].
AB  - A hypothesis has been suggested that the variability of translation machinery is
      one of the key factors of evolutionary transformations of genetic material. It
      considers a module principle of the evolution theory based on the concepts of
      duplication and divergence of genetic material, which is required for origination
      of new genes and proteins with new functions. The duplication results in the
      appearance of pseudogenes, functionally inactive, but serving a material for
      creating new functions. The possible mechanisms changing the translation
      machinery have been considered, which may lead to the sporadic pseudogene
      activation "supplying" natural selection with mutational changes accumulated by
      pseudogenes to assess their adaptive value. This takes into account not only
      potential possibilities of mutational variability of the translation machinery,
      but also the possibility of protein prioritization: a prion mechanism of
      inheritance is also considered which is intensively studied nowadays.

PMID- 11969089
TI  - [New insights into the molecular mechanisms of evolution: stress increases
      genetic diversity].
AB  - The mechanisms of stress-induced mutagenesis in prokaryotes and realization of
      reserved (preaccumulated) genetic variation in eukaryotes are considered. In
      prokaryotes, replication becomes error-prone in stress because of the induction
      of the SOS response and the inactivation of the mismatch repair system; stress
      also increases the transposition rate and the efficiency of interspecific gene
      transfer. In eukaryotes, chaperone HSP90, which restores the native folding of
      mutant proteins (e.g., signal transduction and morphogenetic proteins) in normal
      conditions, fails to do so in stress, which leads to abrupt expression of
      multiple mutations earlier reserved in the corresponding genes. The role of these
      mechanisms in the evolution of prokaryotes and eukaryotes is discussed.

PMID- 11969090
TI  - [Genomic instability in picornaviruses].
AB  - Picornaviruses are small animal RNA viruses and include wtiological agents of
      poliomyelitis, foot and mouse disease, hepatitis A, etc. Replication of their
      genome results in many mutations, which are close in number to a viability
      threshold. Hence every virus population contains a great variety of genomes and
      represents a quasispecies. Covalent rearrangements (deletions, insertions,
      recombination) also contribute to genome variation and arise by replicative and
      nonreplicative mechanisms, which are still poorly understood. Only a minor
      fraction of all new changes is fixed during evolution. The fixation is based on
      two principally different ways of selection: with (positive and negative
      selection) and without (random selection of nonrepresentative variants) regard to
      the phenotype. In natural evolution of picornaviruses, the latter way is
      prevalent, and most fixed mutations are phenotypically neutral. To understand the
      mechanisms of evolution, it is necessary to evaluate the biological significance
      of particular genetic changes. Several new approaches to this problem have
      recently been proposed.

PMID- 11969091
TI  - [Reticulate evolution of parthenogenetic species of the Lacertidae rock lizards:
      inheritance of CLsat tandem repeats and anonymous RAPD markers].
AB  - The genetic relatedness of several bisexual and of four unisexual "Lacerta
      saxicola complex" lizards was studied, using monomer sequences of the complex
      specific CLsat tandem repeats and anonymous RAPD markers. Genomes of
      parthenospecies were shown to include different satellite monomers. The structure
      of each such monomer is specific for a certain pair of bisexual species. This
      fact might be interpreted in favor of co-dominant inheritance of these markers in
      bisexual species hybridogenesis. This idea is supported by the results obtained
      with RAPD markers; i.e., unisexual species genomes include only the loci
      characteristic of certain bisexual species. At the same time, in neither case
      parthenospecies possess specific, autoapomorphic loci that were not present in
      this or that bisexual species.

PMID- 11969092
TI  - [Biophysics of the DNA molecule: a new trend].
AB  - Briefly discussed are experiments with single molecules, representing a novel
      trend in the biophysical study of DNA. The techniques of optical and magnetic
      tweezers whereby external force can be applied to individual DNA molecules were
      used to assess the structural transitions of the DNA double helix under such
      conditions. Discussed are the latest data on the dependence of the rate of
      complementary chain synthesis by DNA polymerase on the stretching of the
      template.

PMID- 11969093
TI  - [Polymorphism of peptide nucleic acid-DNA complexes].

PMID- 11969094
TI  - [Proteomic code].
AB  - On the basis of recent fundamentally novel developments in the protein structure
      a proteomic code is suggested, that would potentially allow to describe sequence,
      structure, and function of proteins by a spectrum of elementary loop-n-lock
      units. All major characteristics of the nearly standard units are described, and
      first five "codons" of the proteomic code are presented with their respective
      unique sequences, structures, and functions. More such codons are to be
      discovered, and the general procedure for their identification is described.

PMID- 11969095
TI  - [Accurate diagnostic methods with the use of molecular colonies].
AB  - The accuracy and reliability of diagnostic tests for infections and cancer can be
      substantially improved by using a gel, rather than a liquid medium, to amplify
      nucleic acids and thereby to obtain molecular colonies.

PMID- 11969096
TI  - [Development of mammalian somatic cell genetics].
AB  - The history of somatic cell genetics from the late 1950s to the present day is
      considered. Studies in this field provided for the elucidation of numerous
      fundamental and applied problems, including spontaneous mutagenesis, gene mapping
      with somatic cell hybrids, and genetic mechanisms of carcinogenesis (e.g., cell
      protooncogenes, oncogenes, and tumor suppressor genes were revealed). The
      knocking-out technique allowed the effects of various genes to be analyzed.

PMID- 11969097
TI  - [The book ''Genome Inconstancy'' in terms of the conceptual history of genetics].

PMID- 11969098
TI  - [Thinking of R.B. ...].

PMID- 11969099
TI  - [Remembering R.B. Khesin].

PMID- 11969100
TI  - While you're busy treating patients, the Iowa Medical Society is working for you!

PMID- 11969101
TI  - How thorough and effective are your follow-up systems?

PMID- 11969103
TI  - Implantable electrical gastric stimulation to treat morbid obesity in the human:
      operative technique.
AB  - BACKGROUND: The surgery to place the implantable gastric stimulator (IGS) is
      described. METHODS: There are two implantable components to the IGS. One is the
      electrical stimulator itself, which is placed in the anterior abdominal wall. It
      is connected to a bipolar lead that is positioned in the muscle wall of the
      stomach. We describe the procedure that is necessary to safely place the
      components. RESULTS: 4 patients have been implanted using techniques that were
      developed and refined around the world. There were no operative deaths. All
      procedures were successfully completed laparoscopically. Two (2/4) connections
      required revision because the leads were not fully inserted into the header of
      the generator. CONCLUSIONS: The operation to implant the IGS is safe and simple
      to perform. Attention to technical details is essential.

PMID- 11969105
TI  - Introduction. Gastric pacing for obesity.

PMID- 11969102
TI  - Gastric pacing as therapy for morbid obesity: preliminary results.
AB  - BACKGROUND: A novel method to treat morbid obesity is presented--gastric
      electrical pacing. Following animal research, human investigation in a total of
      24 patients in three cohorts began in 1995. METHODS: Morbidly obese subjects (BMI
      > or = 40) received electrical stimulation devices in 1995/6 (n = 4), 1998 (n =
      10) and 2000 (n = 10). Electrodes were positioned intramuscularly on the anterior
      gastric wall at the lesser curvature. BMI = body mass index; %EBL = % excess BMI
      (> 25) lost. RESULTS: Patients reported satiety for food with less food. The 2
      patients from the first study followed for > 5 years have achieved 38 and 67
      %EBL. In the second study, every patient lost weight. At 36 months follow-up, the
      mean %EBL was 24 +/- 10 SD (n = 10). CONCLUSIONS: Implantable gastric pacing is a
      safe procedure and causes changes in eating habits in morbidly obese humans,
      resulting in decreased food intake and weight loss.

PMID- 11969104
TI  - Gastric electrical stimulation as therapy of morbid obesity: preliminary results
      from the French study.
AB  - BACKGROUND: Gastric electrical stimulation to treat morbid obesity, using the
      Transcend Implantable Gastric Stimulator (IGS), is being evaluated. We present
      our preliminary results from the French segment of the worldwide study to
      evaluate this therapy. METHODS: Institutionally-approved informed consent was
      obtained from all patients. The IGS is placed laparoscopically. The system has
      two implantable components: 1) a lead with two electrodes that is implanted in a
      gastric lesser curvature muscle tunnel; 2) the lead is connected to an electrical
      pulse generator positioned subcutaneously on the abdominal wall. Two electrode
      positions were used; half (6/12, 50%) were "low" near the pes anserinus, and the
      other 50% "high" nearer the esophagogastric junction. Intraoperative gastroscopy
      is used to diagnose inadvertent gastric perforation. 12 patients (5 M, 7 F) had
      the IGS implanted between July 2000 and February 2001. Mean age was 40.6 years
      (31-51). Mean weight was 122.2 kg (93-146), mean BMI was 42.7 kg/m2 (39.1-48.6),
      and mean excess weight was 60 kg (42-74). Electrical stimulation commenced 1
      month after implantation. RESULTS: All devices were successfully placed
      laparoscopically. There were no deaths or major operative complications.
      Postoperative course was uneventful in all cases. In 25% (3/12), postoperative
      lead dislodgement occurred; 2 of the 3 had their leads replaced. By 9 months,
      mean excess BMI lost was 30 +/- 24% or 16 +/- 12 kg. CONCLUSION: Implanting the
      IGS to treat morbid obesity is technically feasible and safe. Lead dislodgement
      has been simply and satisfactorily corrected. Satisfactory short-term weight loss
      has been achieved in a subset of patients. Long-term efficacy must now be
      determined.

PMID- 11969106
TI  - Implantable gastric stimulation (IGS) as therapy for human morbid obesity: report
      from the 2001 IFSO symposium in Crete.
AB  - This supplement contains reports from a symposium on a novel approach to treat
      obesity, gastric myo-electrical stimulation, that was held at the IFSO in Greece
      in 2001. There were four presentations. Xavier Pi-Sunyer from Columbia University
      in New York discussed medical risks of obesity. Karl Miller from Austria
      presented technical aspects of the surgery. Valerio Cigaina from Italy, the
      originator of the concept, reviewed his 7-year results with this therapy.
      Finally, Jerome D'Argent from France gave his preliminary results employing
      higher energy electrical stimulation parameters. Customarily weight loss data are
      presented as percent excess weight lost (%EWL), an antiquated measurement, e.g.
      all subjects were purchasing life insurance, the poor and minorities were under
      represented and those with heart disease, malignancies or diabetes were excluded.
      In this supplement weight loss data are presented in a novel manner: percent
      excess body mass index (BMI) lost %EBL. This innovation merits an explanation and
      justification. The NIH/NIDDK convened a panel, chaired by Professor Pi-Sunyer,
      that concluded that for adults a BMI of 25 should be considered the upper limit
      of normal. Accordingly, we have proposed that BMI units in excess of 25 be
      considered to represent 100% of the excess weight of an individual. The USA FDA
      has agreed to accept weight loss data presented as %EBL. The intriguing data
      presented justify further evaluation of this novel, potentially useful and
      relatively benign treatment of obesity.

PMID- 11969107
TI  - The medical risks of obesity.
AB  - Obesity is associated with a number of medical conditions that lead to increased
      morbidity and increased mortality. Both the National Institutes of Health and the
      World Health Organization define obesity as a body mass index (BMI) > or = 30
      kg/m2 and overweight as a BMI 25-30. The most common conditions associated with
      obesity are insulin resistance, diabetes mellitus, hypertension, dyslipidemia,
      cardiovascular disease, gallstones and cholecystitis, sleep apnea and other
      respiratory dysfunction, and the increased incidence of certain cancers. These
      are discussed below.

PMID- 11969108
TI  - Sustainability of tsetse control by subsequent treatment of 10% of a previously
      treated Ugandan cattle population with 1% w/v deltamethrin.
AB  - This study was conducted in Masaba and Masafu Sub-counties, Busia District,
      Uganda to assess the effect on the tsetse fly population of first treating all
      cattle with 1% w/v deltamethrin pour-on for a few months, followed by treating
      10% of the cattle population. Treatment of all cattle for 6 months resulted in a
      significant reduction in the density of tsetse flies from 6.3 to 0.1
      flies/trap/day (FTD), a 98.4% reduction. During the same period, the point
      prevalence of bovine trypanosomosis dropped from 37.7% to 2.9% (a 92.3%
      reduction). Treatment was resumed six months later, but this time only 10% of the
      cattle population received the pour-on treatment at three week intervals for a
      period of one year. This treatment maintained the tsetse fly density between 0
      and 0.5 FTD and the prevalence of bovine trypanosomosis generally remained below
      10%. In conclusion, under the local prevailing conditions, treatment of all
      communally grazed cattle with deltamethrin pour-on effectively suppressed the
      Glossina fuscipes fuscipes population. However, subsequent treatment of 10% of
      the cattle probably failed to control the tsetse fly population at a level
      sufficient to reduce trypanosomosis to acceptable levels.

PMID- 11969109
TI  - Efficacy of albendazole and levamisole against gastrointestinal nematodes of
      sheep and goats in Morogoro, Tanzania.
AB  - A study was conducted to determine the efficacy of albendazole after it had been
      withdrawn from use due to the development of resistant strains of nematodes about
      ten years ago. The study also aimed to determine the present efficacy of
      levamisole, which had been recommended to replace albendazole. On one farm, the
      sheep and goats were divided into two groups, one group of each serving as the
      untreated control, while the other was treated with levamisole. The sheep on the
      other farm were divided into three groups, one serving as the untreated control
      group, the second being treated with levamisole and the third being treated with
      albendazole. Faecal samples were collected one day before treatment, and again 10
      days after treatment. Anthelmintic efficacy was determined by the faecal egg
      count reduction test. Ten days after treatment, the sheep treated with levamisole
      on the first farm had a 98% reduction in faecal egg count, with a 95% confidence
      limit of 76%. The goats on the same farm had a 97% reduction in faecal egg count,
      with a 95% lower confidence limit of 81%. At the second farm, 10 days after
      treatment, sheep treated with levamisole had a 99.4% reduction in faecal egg
      count, with a 95% lower confidence limit of 88.9%, whereas the sheep treated with
      albendazole only had a 59.4% reduction in faecal egg count, with a 95% lower
      confidence limit of -19.6%. The study indicated that the gastrointestinal
      nematodes of sheep at the Department of Animal Science and Production farm were
      still resistant to albendazole about ten years after this anthelmintic had been
      withdrawn from use. A reduced efficacy of levamisole was suspected.

PMID- 11969110
TI  - A social approach to the validation of traditional veterinary remedies--the
      Anthra project.
AB  - Anthra, an organization of women veterinary scientists working in the field of
      livestock production and development, has been involved since 1996 in a research
      project to document and validate local ethnoveterinary and animal management
      practices carried out by livestock-rearing communities in different parts of the
      states of Andhra Pradesh and Maharashtra in India. Communal knowledge and
      innovation are an integral part of the day-to-day healing and management
      practices of farmers in all areas and over 80% of farmers continue to use these
      because they are easily and quickly available, especially in remote villages.
      However, this knowledge is today rapidly being lost. Farmers, both men and women,
      have expressed a keen desire to increase their own knowledge of these systems.
      This paper outlines the validation framework evolved by Anthra, wherein farmers
      using these medicines are actively participating in an evaluation process. Major
      findings are that local practices are effective, participating farmers use them
      confidently and other farmers are keen to use and increase their knowledge of
      them.

PMID- 11969111
TI  - Merremia tridentata as a supplementary feed to the grass Panicum maximum for
      young West African Dwarf sheep.
AB  - The provision ad libitum of the browse plant Merremia tridentata as a free-choice
      supplement to the grass Panicum maximum led to a significant increase in the
      total food intake of groups of five West African Dwarf sheep, although the
      increase in weight gain was not significant. The protein content of M. tridentata
      was higher than that of the grass and its tannin content was not sufficient to
      render it unpalatable.

PMID- 11969113
TI  - Replacement of maize with cassava sievates in cockerel starter diets: effect on
      performance and carcass characteristics.

PMID- 11969112
TI  - Hormone profile of crossbred goats during the periparturient period.
AB  - The plasma hormone profile of progesterone, 17 beta-oestradiol, prolactin, growth
      hormone (GH), cortisol, triiodothyronine (T3), thyroxine (T4) and insulin were
      estimated by radioimmunoassay in jugular blood samples from 10 Alpine x Beetal
      crossbred goats during the periparturient period. The plasma progesterone
      concentrations declined from day 20 prior to kidding to the day of kidding and
      then remained at a basal level. 17 beta-Oestradiol concentrations declined from
      day 20 to day 4 prepartum, followed by a continuous increase to reach a peak at
      kidding. Plasma oestradiol declined abruptly on day 1 postpartum and remained low
      throughout the postpartum period. The plasma prolactin concentrations increased
      continuously from day 20 to day 10 prepartum but then increased to a peak on the
      day of kidding, followed by a transient decline by day 5 postpartum. The plasma
      GH concentrations varied significantly (p < 0.01) on the different days of
      sampling but were highest on the day of kidding. The plasma cortisol
      concentration declined from day 20 to day 2 prepartum, after which it abruptly
      increased on day 1 prepartum to reach a peak on the day of kidding. The
      concentrations of plasma T3 remained similar during the prepartum period but were
      minimal on the day of kidding and increased during the postpartum period. The
      concentration of plasma T4 was also lowest on the day of kidding and increased
      during the postpartum period. Plasma insulin concentrations were low in the day
      of kidding.

PMID- 11969114
TI  - Common vetch (Vicia sativa) for improving the nutrition of working equids in
      Campesino systems on hill slopes in Central Mexico.
AB  - Campesino systems on hill slopes in Central Mexico rely on equids for multiple
      activities and have a problem in adequately feeding them. A participatory trial
      was conducted to evaluate the inclusion of common vetch in the traditional forage
      oat crop to improve its feeding value. An agronomic evaluation was undertaken by
      intersowing common vetch at 40 kg seed/ha with oats at 80-100 kg/ha in small
      plots, recording the yield and the chemical composition of the fresh forage in
      ten plots at harvest. The data were analysed as a completely random design,
      taking each farmer/plot as a treatment. A feeding trial compared the live weight
      of 7 donkeys fed oats and vetch against 17 donkeys fed traditional forage. There
      were differences between farmers in forage yields (p < 0.01) that could not be
      explained as due to soil types or management. The mean yield of 31.0 t/ha of
      fresh forage of oats-vetch was 20.5% higher than that from monoculture, and had a
      higher crude protein content. Donkeys fed the oats-vetch were heavier (p <
      0.001). The farmers evaluated the oats-vetch association positively, appreciating
      the higher yields and good condition of their equids. The combination is an
      appropriate technology for these campesino farming systems.

PMID- 11969115
TI  - Detection of subclinical mastitis in dromedary camels (Camelus dromedarius) using
      somatic cell counts and the N-acetyl-beta-D-glucosaminidase test.
AB  - Somatic cell counts, N-acetyl-beta-D-glucosaminidase (NAGase) activity and the
      infection status of the udder were determined in quarter milk samples (n = 86)
      from 22 multiparous, clinically healthy camels, traditionally managed by Bedouin
      nomads in the Negev desert, Israel. Seventy (81.4%) of the 86 samples examined
      contained bacteria, of which 35 (40.7%) gave mixed isolations of two or more
      bacteria, suggesting the existence of subclinical mastitis in the camel herds
      studied. Sixteen samples (18.6%) yielded no growth of bacteria. Staphylococcus
      aureus, Micrococcus spp., Bacillus spp., Streptococcus dysgalactiae and
      Escherichia coli were the main organisms isolated. The somatic cell count (SCC)
      ranged from 1.01 x 105 to 11.78 x 106 cells/ml. NAGase values were between 41.4
      and 372 NAGase units. Quarter milk samples that contained bacteria had
      significantly (p < 0.01) higher mean values for SCC but the mean NAGase levels
      were not significantly different for the bacteriologically negative and positive
      samples. There was a low correlation coefficient (r2 = 0.097) between the SCC and
      NAGase in the quarter milk samples from which bacteria were not isolated (n = 16)
      and a low negative correlation (r2 = -0.038) with the samples that contained
      bacteria (n = 70). The type of bacteria had a significant effect (p < 0.01) on
      the SCC but not on the NAGase activity. Quarter samples from which Staphylococcus
      aureus (coagulase positive) was isolated showed the highest mean SCC and this
      organism is therefore suspected to be the underlying cause of the subclinical
      mastitis. The SCC gave a better indication of the presence of pathogenic
      microorganisms in milk samples than did NAGase.

PMID- 11969116
TI  - Introduction: microbial disease: recent studies show that novel extracellular
      components can enhance microbial resistance to lethal host chemicals and increase
      virulence.

PMID- 11969117
TI  - Helicobacter: a paradigm shift in peptic ulcer disease and more?
AB  - There are many diseases where the cause is unknown and this makes a specific
      treatment difficult. In many cases all that can be achieved is amelioration of
      the illness. Peptic ulcer disease was one such condition no more that 20 years
      ago. The management was drastic--either an operation or life-long medication in
      order to reduce the acid secreted by the stomach. However, the cause of this
      condition was discovered in 1983. Although initially sceptical, the medical
      fraternity now almost universally endorse Helicobacter pylori as the cause of the
      majority of stomach ulcers. Peptic ulcers can now be cured by antibiotics. This
      is a major shift in medical practice. Continued investigations on Helicobacter
      pylori are bringing to light other possible associations with disease as well as
      delineating plausible biological mechanisms for disease pathogenesis.

PMID- 11969118
TI  - Inflammatory bowel disease: is the intestine a Trojan horse?
AB  - Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory condition of
      the intestines that is clinically heterogenous. The cause(s) of IBD are currently
      unknown but the mechanisms of injury are immunological. Increasingly there is an
      emphasis on the study of the complex interactions at the interface of self and
      non-self--the gastrointestinal epithelial surface--in relationship to the
      pathogenesis of disease. There is mounting evidence that a lack of tolerance to
      the normal commensal flora of the intestine may underlie the disease
      pathogenesis. Several genetic loci that are markers of disease susceptibility
      have been identified. These loci map to areas of the genome that are concerned
      with antigen presentation or cytokine secretion and suggest a genetic
      heterogeneity that underlies the clinical differences. Overall a picture is
      emerging of defects in epithelial barrier function and, or immunoregulation
      leading to immune responses that are triggered or exaggerated by the antigenic
      components of the normal flora.

PMID- 11969120
TI  - Prospects for generating new antibiotics.
AB  - A plethora of human pathogens are now resistant to all clinically significant
      antibiotics causing a crisis, in the treatment and management of infectious
      diseases, but also presenting a clear danger to future public health. If drug
      resistance is going to be tackled successfully, new antibiotics must be
      continually developed to counteract the processes of evolution and natural
      selection in these populations of pathogens. Despite the introduction of powerful
      new technologies such as high throughput screening platforms and combinatorial
      chemistry, natural products still offer structural diversity worthy of screening
      for biological activity. Functional genomics can revolutionise rational drug
      design providing new targets for antimicrobial drug discovery. The clusters of
      genes, encoding enzymes that form bio-synthetic pathways leading to the synthesis
      of many natural products including polyketides and non-ribosomal peptides, are
      amenable to modern genetic engineering. Repositioning, deleting and replacing
      genes in these biosynthetic clusters has resulted in the synthesis of many 'un
      natural' natural products. This review examines the engineering of proteins
      involved in chain initiation on polyketide synthases culminating in the
      production at high yield of a biologically active erythromycin derivative.

PMID- 11969119
TI  - Methicillin resistance in Staphylococcus aureus: mechanisms and modulation.
AB  - Staphylococcus aureus is a major pathogen both within hospitals and in the
      community. Methicillin, a beta-lactam antibiotic, acts by inhibiting penicillin
      binding proteins (PBPs) that are involved in the synthesis of peptidoglycan, an
      essential mesh-like polymer that surrounds the cell. S. aureus can become
      resistant to methicillin and other beta-lactam antibiotics through the expression
      of a foreign PBP, PBP2a, that is resistant to the action of methicillin but which
      can perform the functions of the host PBPs. Methicillin-resistant S. aureus
      isolates are often resistant to other classes of antibiotics (through different
      mechanisms) making treatment options limited, and this has led to the search for
      new compounds active against these strains. An understanding of the mechanism of
      methicillin resistance has led to the discovery of accessory factors that
      influence the level and nature of methicillin resistance. Accessory factors, such
      as Fem factors, provide possible new targets, while compounds that modulate
      methicillin resistance such as epicatechin gallate, derived from green tea, and
      corilagin, provide possible lead compounds for development of inhibitors.

PMID- 11969121
TI  - Resistance to antifolates in Plasmodium falciparum, the causative agent of
      tropical malaria.
AB  - Every year there are 270 million clinical attacks of malaria and 2 million
      deaths, caused by the protozoan Plasmodium falciparum. Most of these cases occur
      in Africa. Chloroquine-resistance has led to reliance on anti-malarial
      antifolates, in particular the synergistic combination sulfadoxine/pyrimethamine
      (S/P) which targets enzymatic synthesis of folate co-factors through
      dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). Resistance to
      S/P is now increasing and replacement antimalarials are needed. Crystal
      structures are not yet available for these key enzymes in the folate pathway.
      This review focuses on the activity of drugs on DHFR in malaria parasites,
      attempts to interpret differences in activity of pyrimethamine and its related
      drugs, and to clarify how residue changes due to point mutations determine the
      development of resistance. In homology-modelled P. falciparum DHFR (PfDHFR), the
      typical structure of four alpha-helices, 8-stranded beta-sheet, four Loops and
      eight Turns is clearly seen. Long polar sequences specific for Plasmodium are
      inserted in Turns 1 and 2. Structures immediately concerned in drug binding are
      beta-A, L1, alpha-B, alpha-C, T-3, beta-E, alpha-F, and beta-F. The roles of
      several mutations associated with resistance are discussed. In view of sequence
      differences in turn 3 in PfDHFR and in the human enzyme, and the marked
      interaction with residues of T3 of the experimental flexible antifolate WR99210
      effective in pyrimethamine and cycloguanil resistance, further drug development
      in this area is indicated.

PMID- 11969122
TI  - Rifampicin resistant leprosy: a review and a research proposal of a pilot study.

PMID- 11969123
TI  - Socio-cultural aspects of leprosy among the Masalit and Hawsa tribes in the
      Sudan.
AB  - Social and cultural factors influencing knowledge, attitudes and practices (KAP)
      towards leprosy in two communities in eastern Sudan were studied to determine
      their effects on treatment seeking and compliance. The study was qualitative
      using focus small group discussions, personal interviews and direct observation.
      The target populations were Masalit and Hawsa, the two main tribes in the area.
      Knowledge about the pathological cause of leprosy was lacking but the clinical
      manifestations were well recognized, particularly among the Masalit, in whom the
      disease in more common than the Hawsa. Among the Masalit there was a widely held
      belief that leprosy was caused by eating meat of the wild pig and a certain type
      of fish. The Hawsa, who are more devout Muslims, do not eat pig and associate
      leprosy with consumption of two types of fish. Between both tribes, the stigma of
      leprosy was not strong and the degree of rejection was more towards those with
      severe disease, particularly patients with ulcerated lesions and severe
      deformities. Patients were cared for by the family and lived in a separate hut
      within the families' housing compounds. In this remote area where medical
      services are scarce or nonexistent, those interviewed did not realize that
      leprosy was treatable by modern medicine. This influenced the treatment-seeking
      behaviour of patients, who were often treated by spiritual healers and other
      traditional medicine practices. With the introduction of multidrug therapy and
      health education of patients and society, many more patients are now seeking
      medical treatment, indicating a change in health seeking behaviour.

PMID- 11969124
TI  - Trends in prevalence and case finding in the ALERT leprosy control programme,
      1979-1999.
AB  - From 1979 to 1999, the ALERT leprosy control programme has covered a well-defined
      area in central Ethiopia using standardized case finding strategies. During this
      period, the leprosy prevalence has decreased more than 30-fold, there has been a
      3-fold decrease in case detection and a 6-fold decrease in the case detection
      rate. The proportion of MB patients among new cases increased by around 80% and
      the proportion of children among new cases decreased by around 60%. Several
      factors may have contributed to these trends. The impact of the introduction of
      MDT and the shortening of the duration of the MB regimen are shown, but other
      factors are also discussed at length: an increase in the population of the area,
      cleaning up of the registers, changing case definitions, changes in staff
      motivation and fluctuations, even small ones, in case finding intensity and
      coverage. Do the observed trends reflect a reduction in the transmission of the
      leprosy infection? Because of the many confounding factors, it would be difficult
      to answer that question positively at present. Additional rigorous data
      collection and analysis is required.

PMID- 11969125
TI  - Typing of clinical isolates of Mycobacterium leprae and their distribution in
      Korea.
AB  - Although there is no genetic diversity in isolates of Mycobacterium leprae, the
      variance of tandem repeats in the rpoT gene was recently demonstrated. We have
      typed clinical isolates of M. leprae in Korea using difference of the tandem
      repeats in the rpoT gene. Among 69 patients, 65 Korean isolates (94.2%)
      demonstrated four copies of the 6 bp tandem repeat (GACATC) in the rpoT gene, and
      incidences of three copies were found in only two Koreans and two foreigners
      (2.9%, respectively).

PMID- 11969126
TI  - Avoiding misperceptions: classifying rehabilitation projects using letters rather
      than numbers.
AB  - A classification system proposed earlier of the many different known
      rehabilitation approaches and activities used a quantitative scoring system, thus
      giving the impression that projects with a higher score were better, more correct
      or more important than projects with a lower score. We therefore propose an
      alternative classification based on letters, so that a given combination of
      letters characterizes a particular type of project. The letters are derived from
      four dimensions: desired outcome of the intervention, participation of the
      clients in the rehabilitation process, the target group served and the services
      offered. Some examples are presented. The classification serves to analyse
      rehabilitation projects, to define policy and as a starting point for evaluation.

PMID- 11969127
TI  - Lymphatics in leprosy: relationship to elastic fibres and observations following
      intra-lesional injections of colloidal carbon.
AB  - An investigation of skin lymphatics in leprosy has been undertaken. Examination
      of 62 skin biopsies from 31 patients with various classifications of leprosy has
      revealed dilated initial lymphatics within granulomas of lepromatous leprosy, but
      no significant abnormalities in non-lepromatous disease or in non-granulomatous
      skin. Colloidal carbon injected intra-lesionally failed to appear within
      granulomas, but could be seen in lymphatics in non-granulomatous dermis. Elastic
      fibres were also absent within granulomas. AFB were clearly identified within
      endothelial cells of initial lymphatics. We suggest lymphatic malfunction may be
      compartmental, existing only within the granulomas and not in the surrounding
      normal appearing dermis.

PMID- 11969128
TI  - The pathology of HIV infection.
AB  - The acquired immunodeficiency syndrome (AIDS) is the result of a human
      immunodeficiency virus (HIV) infection damaging the cell-mediated immune system.
      A wide range of opportunistic infections (OI) and tumours develop; additionally,
      HIV directly damages some organs. The patterns of opportunistic diseases (OD) are
      different in different parts of the world, depending on the local prevalence of
      latent and acquired infections and on the survival of HIV-infected patients. OD
      patterns change as people migrate. Recently introduced highly active anti
      retroviral chemotherapy prevents many of the common OIs, but also introduces a
      new range of toxic pathological damage. Longer survival permits development of
      new HIV-related diseases. The pathology of HIV/AIDS is not static but changing.

PMID- 11969129
TI  - Hepatic involvement in lepromatous leprosy.
AB  - Hepatic involvement in a lepromatous leprosy (LL) patient is reported. The serum
      concentrations of aminotransferases were much higher than previously described in
      the leprosy literature. Other causes for hepatic damage were ruled out. Such
      hepatic involvement and elevation of aminotransferases have never been described
      in leprosy.

PMID- 11969130
TI  - Biporalis keratomycosis in a leprosy patient: a case report.

PMID- 11969131
TI  - Bacterial index of granuloma and its relevance compared to BI of skin smears.

PMID- 11969133
TI  - Educational conferences on leprosy: experiences from a non-government hospital in
      Paraguay.

PMID- 11969132
TI  - Effectiveness of midwives in the retrieval of defaulting leprosy patients in
      urban Yangon, Myanmar.

PMID- 11969134
TI  - Leprosy control in a prefecture of Yunnan Province in the Peoples' Republic of
      China, using intensive health education of the public and primary health care
      workers for the detection of cases, 1998-1999.

PMID- 11969135
TI  - Socio-economic rehabilitation in leprosy--an example.

PMID- 11969136
TI  - Progress towards development of immunoassays for detection of Mycobacterium
      leprae infection, employing 35kDa antigen: an update.
AB  - The 35 kDa antigen of Mycobacterium leprae is a membrane component that contains
      both B and T-cell stimulating epitopes. Monoclonal antibodies, primarily specific
      to M. leprae, have been developed against this antigen. Moreover, this antigen
      has been genetically engineered. Using recombinant 35 kDa antigen and/or a
      monoclonal antibody against an epitope on 35 kDa, a variety of antibody/antigen
      detecting tests have been described for detection of M. leprae infection. 35 kDa
      protein also stimulates peripheral blood mononuclear cells (PBMCs) from the
      majority of paucibacillary (PB) patients. Approaches using combined antibody and
      T cell are discussed.

PMID- 11969137
TI  - Methylmercury in the hair of subsistence food users in a rural Alaskan village.
AB  - The level of methylmercury in the hair of 16 rural Alaskan subsistence food users
      from Napakiak, a small Yup'ik Eskimo village on the Kuskokwim River in southwest
      Alaska, was assessed. A non-subsistence population of 20 non-Yup'ik adults from
      the urban interior city of Fairbanks was used as a comparison group. The Napakiak
      Yup'ik had a mean methylmercury concentration in hair of 1.45 ppm with a range of
      0.32-4.00 ppm, while the Fairbanks population had a mean concentration of 0.19
      ppm with a range of 0.03 to 0.43 ppm in their hair. Comparison with an earlier
      study by Galster (1976) from this region, suggests that no increase in exposure
      to mercury has occurred in subsistence food users. The methylmercury levels in
      hair in the rural village population, although higher than the urban group, are
      well below the World Health Organization (WHO) safety limit of 10 ppm.

PMID- 11969138
TI  - Physical Education Bill.

PMID- 11969139
TI  - Warfarin usage in Alaska: a quality improvement study.
AB  - This study represents a snapshot view of a possible area for quality improvement
      work. We realize that a variety of events may have contributed to the deaths that
      occurred in our study cohort. In addition, the small number of cases reviewed
      precludes the formulation of conclusive statements regarding warfarin use in
      Alaska. Nevertheless, we are reporting the results in the hope of raising
      awareness in the Alaska medical community about the use of warfarin in treating
      atrial fibrillation and the benefits this therapy may have for the elderly
      patient.

PMID- 11969140
TI  - Risk factors for osteoporosis in Alaska Native women: a cross-sectional survey.
AB  - OBJECTIVES: To estimate the prevalence of risk factors for osteoporosis in Alaska
      Native (AN) women and to assess the feasibility of portable bone density
      measurement in rural Alaska. METHODS: We conducted a cross-sectional survey of a
      convenience sample of 452 patients from 17 clinics in Alaska. We interviewed
      subjects regarding risk factors for osteoporosis and measured calcaneal bone
      density by ultrasound. RESULTS: Of the 452 women, 316 (70%) were Alaska Natives.
      Risk factors for osteoporosis were common among study participants. Total dietary
      calcium intake was low (mean = 306 mg/day). Current smokers [Odds Ratio (OR) =
      3.9, 95% Confidence Interval (95% C.I.) 1.8, 8.4], former smokers (OR = 2.8, 95%
      C.I. 1.3, 6.2) and chronic users of oral steroids (OR = 4.7, 95% C.I. 1.8, 12.0)
      were at increased risk for low bone density. CONCLUSIONS: Reduction of cigarette
      smoking, increase in dietary calcium, and reduction of oral steroid use would
      likely decrease the prevalence of osteoporosis in AN women. A comprehensive
      prevention program including bone density screening is warranted in rural Alaska.

PMID- 11969141
TI  - Pain, sedation and morphine metabolism in cancer patients during long-term
      treatment with sustained-release morphine.
AB  - BACKGROUND: Morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) are
      the two most important metabolites of morphine. Both are pharmacologically
      active, however, with different effects. M-6-G has been demonstrated capable of
      inducing anti-nociception and sedation, and M-3-G may induce behavioural
      excitation and possibly antagonise anti-nociception. Their impact on
      pharmacodynamics in patients in long-term treatment with oral morphine remains to
      be settled. METHODS: Forty-two cancer patients treated with oral sustained
      release (SR) morphine were assessed for pain, sedation and other side effects
      related to morphine treatment. Blood samples were analysed for morphine, M-3-G
      and M-6-G by high-performance liquid chromatography (HPLC). RESULTS: Significant
      correlations were found between the daily dose of SR morphine and plasma morphine
      (M) (r = 0.535, P < 0.001), plasma M-6-G (r = 0.868, P < 0.001) and plasma M-3-G
      (r = 0.865, P < 0.001). There was no relationship between plasma morphine, M-6-G,
      M-6-G/M and pain and sedation scores. Seventy-nine percent of the patients
      suffered from dryness of the mouth, which was the most frequent side effect
      observed. Patients in this group had higher plasma morphine and M-6-G
      concentrations than patients who did not suffer from this side effect.
      CONCLUSION: The plasma concentrations of morphine and its metabolites, M-3-G and
      M-6-G, are significantly correlated to the daily dose of SR morphine. Although M
      6-G has analgesic properties, no associations were found between pain and plasma
      morphine and morphine metabolites. This may be due to the multitudinous factors
      affecting the dose-effect relationship. Patients with dryness of the mouth had
      higher concentrations of morphine and M-6-G than patients without this side
      effect.

PMID- 11969142
TI  - Which cancer patients are referred to Hospital at Home for palliative care?
AB  - Previous research has shown that palliative home care use is influenced by
      variables such as age, socioeconomic status, presence of an informal carer,
      diagnosis, and care dependency. However, there is little information on its
      association with other health service use. This study compared 121 cancer
      patients referred to Hospital at Home (HAH) for palliative care with a sample of
      206 cancer patients not referred who died within the same period. Electronic
      record linkage of NHS databases enabled investigation of patients' total input of
      care in their last year of life. Univariate analysis showed that patients
      referred to HAH were younger, lived in less deprived areas, were less likely to
      have been diagnosed within a month of death and to have causes other than cancer
      recorded on their death certificate. They were furthermore more likely to have
      had specialist oncology input, Macmillan nursing, Marie Curie nursing, acute
      hospital care, and district nursing before their last month of life. When care
      was received, patients referred to HAH received more hours of district nursing
      care. However, patients not referred to HAH began their acute hospital and
      district nursing input earlier (further from death) than those referred.
      Multivariate logistic regression analysis showed HAH referral to be negatively
      associated with breast and genitourinary cancers and number of noncancer causes
      recorded on the death certificate. Referral was significantly positively
      associated with specialist oncology input, Marie Curie nursing, and a late start
      (close to death) of acute hospital and district nursing care. It is hypothesised
      that referral to palliative home care is more likely among patients who have had
      prior contact with cancer services or are most clearly identified as cancer
      patients, and whose illness progression is manifested by a relatively short but
      intensive period of care prior to death.

PMID- 11969143
TI  - The essence of spiritual care: a phenomenological enquiry.
AB  - This study used a phenomenological approach, founded on the Husserlian tradition,
      to discover the spiritual essence of palliative care in the lived experience of
      stakeholders. Semistructured interviews were conducted with 16 participants who
      held a variety of roles linked to palliative care, and were of different
      religions and none. Amongst these participants, spiritual care is based on the
      assumption that all people are spiritual beings. It recognizes the relationship
      between illness and the spiritual domain and acknowledges the possibility of a
      search for meaning in the big questions of life and death. It responds to
      religious and humanistic needs by meeting both the requirements of faith and the
      desire for another human being to 'be there'. Fundamentally, spiritual care seeks
      to affirm the value of each and every person based on non-judgemental love.

PMID- 11969144
TI  - Spirituality in palliative care: opportunity or burden?
AB  - The article questions an assumption in palliative care literature, namely that
      all patients have a spiritual dimension and that all staff can offer spiritual
      care. The article identifies spirituality as a particular kind of discourse. In
      late-modern Anglophone societies, this discourse arises from the experience of a
      particular generation and a particular segment of the population, namely those
      moving beyond formal religion; this segment is probably better represented among
      caring professionals than among dying patients. A four-fold typology of patients'
      approaches to religion/spirituality is developed, indicating the potential of
      differentiating between actual patients, rather than presuming a universal
      'search for meaning'. This alternative approach may enhance opportunities for
      team working and reduce the likelihood of any one member of staff feeling
      spiritual care to be an unwelcome burden.

PMID- 11969145
TI  - A scale to measure satisfaction of bereaved family receiving inpatient palliative
      care.
AB  - Although satisfaction is an important outcome of medical care, there are no
      validated tools to quantify family satisfaction with hospital-based palliative
      care. In this nationwide postal survey, an instrument to measure informal carer
      satisfaction with an inpatient palliative care service was validated. A 60-item
      questionnaire was mailed to 1344 bereaved people who had lost their family
      members at 50 palliative care units in Japan, and 850 responses were analysed
      (response rate = 64%). The reliability, construct validity, and convergent
      validity of the scale were examined after the responses were randomly divided
      into two groups: a training set used in the development phase (n = 500) and a
      testing set used in the validation phase (n = 350). The number of scale items was
      reduced from 50 to 34 through psychometric techniques in the development phase.
      In the testing sample, the overall Cronbach's coefficient alpha for the final 34
      item scale was 0.98. A factor analysis revealed that the scale consisted of seven
      subcategories: Nursing Care, Facility, Information, Availability, Family Care,
      Cost, and Symptom Palliation. The total score of the scale was significantly
      correlated with the degree of global satisfaction of the bereaved (Spearman's rho
      = 0.78). In conclusion, this 34-item scale, the Satisfaction Scale for Family
      Members Receiving Inpatient Palliative Care (Sat-Fam-IPC), has acceptable
      psychometric properties and would be a useful tool to measure carer satisfaction
      with an inpatient palliative care service.

PMID- 11969147
TI  - Family support: a summer holiday programme for Maltese children.

PMID- 11969146
TI  - The current status of bereavement follow-up in hospice and palliative care in
      Japan.
AB  - In order to explore the implementation of bereavement care in hospice/palliative
      care settings in Japan, a self-administered questionnaire was sent to all 54
      government-approved hospice/palliative care units (PCUs) in May of 1999 (recovery
      rate 93%). Results showed that bereavement follow-up is performed in 37
      institutes (74%) and memorial cards and services are most frequently provided.
      Memorial cards are provided mainly by nurses, and memorial services involve many
      health care professionals as well as volunteers. Religious workers tended to be
      involved in memorial services and social group meetings. Individually oriented
      interventions such as telephone contacts, personal visits and personal
      counselling were reportedly used less often. The need for individual-oriented
      programmes was recognized, and many institutes were considering the expansion of
      their programmes to include them. However, the difficulties of implementing such
      care at hospice/PCUs were also raised. Two socio-cultural factors possibly
      affecting bereavement care in Japan, namely, the roles of family and religious
      (Buddhist) ceremonies were discussed. It was pointed out that the spirit of
      bereavement care may be embodied in existing religious ceremonies. We conclude
      that it is necessary to develop bereavement care programmes based on common,
      basic hospice care tenets while making full use of existing local resources and
      taking into account regional values.

PMID- 11969148
TI  - Recruiting into palliative care trials: lessons learnt from a feasibility study.

PMID- 11969149
TI  - Communication in lung cancer.

PMID- 11969150
TI  - The use of psychostimulants by palliative care consultants in the UK: a
      retrospective telephone survey.

PMID- 11969151
TI  - Children's hospices: organizational and staff issues.

PMID- 11969152
TI  - Depression in advanced disease: a systematic review Part 1. Prevalence and case
      finding.
AB  - OBJECTIVE: To identify all literature regarding depression in patients with
      advanced cancer and among mixed hospice populations, and to summarise the
      prevalence of depression according to different definitions. METHODS: A
      systematic review was performed using extensive electronic and hand searches. All
      studies with quantitative data on prevalence of depression were included and
      categorised according to their definition of depression. RESULTS: We identified
      46 eligible studies giving information on the prevalence of depression, and a
      further four which gave information on case finding. The most widely used
      assessment of depression was the Hospital Anxiety and Depression Scale (HADS),
      which gave a median prevalence of 'definite depression' (i.e., a score on the
      depression subscale of > 10) of 29%, (interquartile range, IQR, 19.50-34.25%).
      Studies that used psychiatric interviews indicated a prevalence of major
      depressive disorder ranging from 5% to 26%, with a median of 15%. Studies were
      generally small (median sample size 88.5, IQR 50-108), had high numbers of
      nonresponders, and rarely gave confidence intervals for estimates of prevalence.
      CONCLUSIONS: Depression is a common problem in palliative care settings. The
      quality of much of the available research is poor, based on small samples of
      patients with very high nonparticipation rates. The clinical importance of
      depression is described in subsequent papers.

PMID- 11969153
TI  - Paediatric respite care: a literature review from New Zealand.
AB  - This paper reviews relevant international and New Zealand literature, policy
      documents and reports on respite provision for children who are dying and their
      families. The literature describes why respite care for children is necessary,
      and evaluates present respite services in accord with recent reports and
      literature. The service provisions needed for dying children and their families
      are explored, including suggestions for the improvement of services and future
      research. The literature reveals that, although respite care for terminally ill
      children and their families is necessary, service provisions are uncoordinated,
      not always culturally sensitive and very limited for children and their families.
      Improvement in paediatric respite services is necessary and research needs to be
      conducted in this area to facilitate the development of more appropriate respite
      services for children and their families.

PMID- 11969154
TI  - [Comparative approach to correction of annotated gene starts in complete
      bacterial genomes].
AB  - A method for refining the beginnings of genes and a search for shifts of the
      reading frame is proposed. The method is based on a comparison of nucleotide and
      amino acid sequences of homologous genes of related organisms. The algorithm is
      based on the fact that the rate of changes in the protein-coding regions of the
      genome is substantially lower than that of noncoding regions. A modification of
      the Smith-Waterman algorithm is proposed, which makes it possible to align the
      amino acid sequences obtained by formal translation of the starting nucleotide
      sequences by taking into account a possible shift of the reading frame. The
      algorithm has been implemented in the package of ORTOLOGATOR-GeneCorrector
      programs. Testing the program showed that the approach enables one to detect a
      wrong annotation of the beginnings in 1% of genes (even in well-studied organisms
      such as Escherichia coli) and identify several (approximately 10) shifts of the
      open reading frame. Thus, the algorithm can be used at both the initial and final
      stages of analysis of the genome.

PMID- 11969155
TI  - [Analysis of hepatitis C virus proteins based on amino acid sequence data and
      literature data].
AB  - To analyze the interrelationships between the amino acid sequences of the
      proteins of hepatitis C virus and the functional characteristics of different
      variants of this virus, a database of protein functional mapping of hepatitis C
      virus was developed. The database contains amino acid sequences (both full-size
      and fragmentary) retrieved from accessible databases and experimental data
      published in literature. The database also contains the results of comparison and
      treatment of primary data, including alignments and functional regions. On the
      basis of these data, variable and conservative regions of envelope proteins of
      hepatitis C virus were revealed. Antigenic and functional maps of structural and
      nonstructural proteins of the virus were constructed. The most variable region of
      the envelope protein E2 (HVR1) was analysed. It is assumed that the conservatism
      of some amino acid positions of HVR1 is related to the functions of this region.

PMID- 11969156
TI  - [Kinetic characteristics of luminol chemiluminescence caused by chloramine
      compounds].
AB  - The decaying part of the kinetic curves of luminol chemiluminescence (0.02 mM)
      induced by N-chlorphenylalanine is approximated by an exponential dependence,
      which varies insignificantly as chloramine concentration is changed from 0.2 to
      0.7 mM. On the whole, the chemiluminescence of luminol is a result of its
      oxidation, which occurs in three stages with the formation of two intermediate
      products. N-Chlorphenylalanine is involved in the process at the initial stage.
      The reciprocal of the time the luminescence reaches a maximum increases linearly
      with the growth of N-chlorphenylalanine concentration. According to the
      calculations using the equations that reflect three stages of luminol conversion
      in the presence of excess chloramine, the rate constant for the initial stage is
      about 10(3) l/(mol.min). The rate constant for one stage of the conversion of
      luminol oxidation product is approximately 0.2 min-1, and the rate constant of
      the other is severalfold greater. Luminol chemiluminescence induced by low
      concentrations of N,N-dichlortaurine is more durable. Probably, it is composed of
      two types of emission one of which slowly decays.

PMID- 11969157
TI  - [Molecular dynamics of oligopeptides. 4. Dynamic characteristics of frequently
      and rarely occurring dipeptide fragments of proteins].
AB  - The existence of differences in the dynamic organization of frequently and the
      rarely occurring dipeptide fragments in globular and membrane proteins was shown.
      The dynamic isomorphism and the collective degrees of freedom in these fragments
      were analyzed. A topological classification of the maps of the levels of free
      energy for pairs of dihedral angles of the main chain and side residues was
      carried out.

PMID- 11969158
TI  - [Domain structure of CAF1M protein from Yersinia pestis. Structure and the role
      of various domains].
AB  - The cooperative structure of Caf1M from Yersinia pestis was studied using
      scanning microcalorimetry, fluorescence, and limited proteolysis. It was shown
      that, in Caf1M-Hg (a derivative in which the disulfide bond is replaced by an S
      Hg-S bond), the first to melt is the N-domain. Then the C-domain melts. After
      renaturation in a buffer with a low NaCl concentration, only the C-domain is in
      the native state, and it can be obtained by limited proteolysis. After
      renaturation in a buffer with a high NaCl concentration, only the N-domain is in
      the native state, and it can be obtained by limited proteolysis. Both domains
      have native structure; however, only the N-domain interacts with Cafl (natural
      substrate for Caf1M).

PMID- 11969159
TI  - [Transformation of chemical energy in biomolecular systems with hydrogen bonds].
AB  - The mechanism underlying the excitation of the hydrogen bond with ATP hydrolysis
      was considered. Coulomb interactions of the proton of the hydrogen bond A-H...B
      with the electrical field of the covalent bond of ADP-P were calculated. It was
      shown that the electrical field of the covalent bond of ADP-P excites
      oscillations of the proton in the complex with the hydrogen bond A-H...B and
      displaces it from the equilibrium towards the covalent bond. The distortion of
      the potential curve depends on a change in the length of the covalent bond of ADP
      P. Adiabatic potentials U0 and UN of the ADP-P system were calculated, which
      correspond to the ground and excited states of the H-bond proton. It was found
      that as the length of the bond of ADP-P (rho) increases, the branches of the
      adiabatic potential U0(rho) and UN(rho) intersect. At the intersection point, the
      system can transit to the branch UN(rho), which can lead to a reduction of the
      barrier and a break of the covalent bond of ADP-P. Presumably, this mechanism is
      universal for processes of transformation of the chemical energy of ATP to the
      energy of excited hydrogen bond, a mechanism for the maintenance of heat balance
      and reduction of entropy in a living organism.

PMID- 11969160
TI  - [Dynamic properties of water bound to matrices of natural DNA and model
      complexes].
AB  - From experimental data on the hydration energetics of nucleic acids obtained by
      differential scanning calorimetry under isothermal conditions, dielectric
      relaxation time tau d and "free volume" Vf occupied by water molecules in
      hydration shells of natural DNA and model polyribonucleotides were calculated. In
      addition, systems consisting of dinucleotides ApA, TpT, UpU, TpU, UpT and water
      clusters of various sizes (from 20 to 400 water molecules) were studied by Monte
      Carlo computer simulation. It was shown that, as water content in systems
      increases, the dynamic characteristics of bound water obtained with both methods
      approached the values for bulk water.

PMID- 11969161
TI  - [Interaction of meso-tetra(N-hydroxyethylpyridyl)porphyrins with DNA. Effect of
      position of peripheral groups].
AB  - The interaction of meso-tetra(4-N-oxyethylpyridyl)porphyrin and its 3-N
      substituted analogue with DNA was studied by UV spectrophotometry and circular
      dichroism methods. It was shown that the position of the side group on the
      pyridyl ring substantially affects the mechanism of interaction with DNA. 4-N
      oxyethylpyridyl porphyrins more preferably intercalate into the DNA structure but
      worse realize the external binding than 3N-porphyrins.

PMID- 11969162
TI  - [Fluorescence of meso-tetrakis(4-(carboxy)phenyl)porphine covalently bound to
      oligonucleotides d(CG)5 and d(TA)5].
AB  - The amino-reactive derivative of tetraphenylporphine meso-tetrakis[4
      (carboxy)phenyl]porphine (TCPP) was synthesized, which is characterized by a high
      molar absorption coefficient (epsilon 416 = 36,500 M-1.cm-1). TCPP was covalently
      attached to oligonucleotides d(CG)5 [d(CG)5-TCPP] and d(TA)5 [d(TA)5-TCPP]. The
      spectral characteristics of these complexes were studied in 0.01 M phosphate
      buffer, pH 7 at 23 degrees C. UV-visible absorption spectra of these complexes
      have a clearly pronounced Soret band at (414 +/- 1) nm for d(CG)5-TCPP and at
      (412 +/- 1) nm for d(TA)5-TCPP. The fluorescence spectra of these complexes have
      maxima at (648 +/- 2) nm for d(CG)5-TCPP and at (658 +/- 2) nm for d(TA)5-TCPP.
      In this study we also determined fluorescence quantum yields q and fluorescence
      lifetimes tau [q = 0.099 +/- 0.011, tau = (9.0 +/- 0.3) ns for d(CG)5-TCPP and q
      = 0.080 +/- 0.011, tau = (8.7 +/- 0.3) ns for d(TA)5-TCPP]. A temperature rise
      from 5 to 50 degrees C produced only slight (within 23%) emission changes in both
      samples studied. Taking into account: a) high fluorescence yields (q), b) weak
      dependence of q on temperature, c) weak q dependence of q on the oligonucleotide
      type, we conclude that TCPP may be used as a sensitive fluorescence label in DNA
      studies.

PMID- 11969164
TI  - [New spatial-temporal dynamics in a reaction-electrodiffusion system].
AB  - The properties of a system reaction-electrodiffusion were studied using two
      component model of interaction and diffusion of charged particles near membrane
      in solutions of low ionic strength to which traditional assumptions about local
      electroneutrality of medium are not applicable. It is shown that the effect of
      self-consistent electric field leads to bistability, the appearance of localized
      structures with contrast charge distribution and regimes aperiodical in time and
      in space.

PMID- 11969163
TI  - [Effect of water soluble non-membrane proteins on the phospholipid structure].
AB  - The interaction of water-soluble nonmembraneous proteins (trypsin and the basic
      pancreatic trypsin inhibitor (BPTI)) with soybean phospholipids was studied using
      multilamellar vesicles. Multilamellar vesicles were obtained from soybean lipid
      extracts and mixtures of individual phospholipids based on phosphatidylcholine.
      These mixtures contain different phospholipids: "bilayer", "nonbilayer", and
      negatively charged. It was shown that the content of both proteins in the complex
      depends on pH and the presence of negatively charged components. On the basis of
      this finding, the conclusion about the electrostatic nature of lipid-protein
      interaction was made. The structural organization of soybean phospholipids in
      multilamellar vesicles was studied in the presence and absence of the proteins
      using broad-line 31P-NMR spectroscopy. It was found that, in mixtures of
      phospholipids of complex composition, different types of phases coexist, and
      phospholipids of different classes can compensate the effects of each other.
      Trypsin and BPTI affect the structure of phospholipids in a similar way, inducing
      considerable structural changes in multilamellar vesicles of preparations
      containing negatively charged components in whose structure there coexisted
      primordially the bilayer and isotropic phases.

PMID- 11969165
TI  - [Modeling of energy migration and trapping in purple bacteria. Analysis of
      extreme formulae].
AB  - Homogeneous pigment ensembles similar to those of purple bacteria Rhodospirillum
      rubrum were studied. Two formulae were advanced for the limiting values of
      excitation lifetime and quantum yield of excitation trapping in these ensembles,
      provided all reaction centers are in an active state. It was demonstrated by
      mathematical modeling that these limiting values strictly depend on three
      parameters of molecular ensembles: the numbers of core-bacteriochlorophyll
      molecules per reaction center, the values of rate constants for excitation
      trapping in reaction centers, and excitation wasteful deactivation in all
      molecules. The excitation lifetime and quantum yield were proved to approach
      their limiting values as the rate constants of excitation intermolecular
      migration increase. The closeness of experimental values for two above mentioned
      functions to their calculated limiting values proves the migration-limited type
      of the photosynthetic unit investigated and a high efficiency of excitation
      trapping in its reaction centers.

PMID- 11969166
TI  - [The role of reactive oxygen species in copper-induced permeability of plasma
      membranes in Escherichia coli].
AB  - The role of active oxygen species in the induction of nonselective cationic
      permeability of the plasma membrane of bacteria Escherichia coli B by the action
      of Cu2+ ions was studied. It was found that the increase in the amount of active
      oxygen species in the suspension after treating cells with copper occurred
      synchronously with the leakage of K+ cations from them. Evidence is presented
      that active oxygen species formed during the interaction of copper ions with
      bacteria under aerobic conditions are not involved in the induction of channel
      conductivity in the membrane. Moreover, the ability of oxygen to protect the
      membrane from the toxic action of copper was shown, and the activation of
      membrane damage by external reductants was confirmed. These data suggest that the
      barrier properties of the membrane are disturbed during the interaction of Cu+
      ions with critical targets on the surface, the concentration of Cu+ being
      determined by all redox processes in the near-membrane space.

PMID- 11969167
TI  - [Effect of intracellular ATP on La(3+)-induced aggregation and fusion of human
      erythrocytes].
AB  - The influence of intracellular ATP level on the aggregation and fusion of human
      erythrocytes, induced by La3+ in the concentration range 20-330 microM was
      studied. The aggregation of intact red blood cells differs from that of cells
      with increased and decreased contents of ATP. Incubation of erythrocyte
      aggregates at 37 degrees C did not lead to cell fusion. At the same time,
      incubation of erythrocyte aggregates with decreased and increased ATP contents in
      the presence of La3+ induced a pronounced cell fusion.

PMID- 11969168
TI  - [Stimulation and inhibition of Escherichia coli cell growth during cultivation in
      the catholyte and anolyte of culture medium].
AB  - The effect of pretreatment of growth medium M-9 with direct electric current in
      the cathode and the anode compartments of a diaphragm electrolyzer on the growth
      of Escherichia coli cells was studied. The cells were cultured separately in the
      catholyte and the anolyte of the growth medium. The cell growth was registered as
      a change in optical density of the culture suspension by the method of
      turbidimetry. It was found that cells grown in the catholyte at a temperature of
      37 degrees C yielded a 20-30% increase in amount as compared to the control. No
      cell growth was observed in the anolyte, and a part of the initial cells were
      lysed. Possible mechanisms of stimulation and inhibition of cell growth and the
      reasons of discrepancies in the earlier published data are discussed.

PMID- 11969169
TI  - [Effect of an aqueous salt solution exposed to weak magnetic fields on the
      sensitivity of bacterial plasma membrane to reactive oxygen species].
AB  - It was shown by electroorientation spectroscopy that hydroxyl radicals OH*
      generated in a Cu(2+)-ascorbate system disturb the barrier properties of the
      plasma membrane in Escherichia coli K12 cells. It was also found that in water
      containing small additions of H+, Na+, and Cl-, preliminarily exposed to weak
      combined permanent (42 microT) and polyfrequency alternating (amplitude 0.06
      microT and frequencies 1, 3.7, and 32.2 Hz) magnetic fields, the sensitivity of
      the plasma membrane to the radical attack considerably decreased, whereas
      dimethylsulfoxide did not protect active oxygen species in this system. It was
      assumed that treating the aqueous solution with magnetic fields affects the
      oxidation of ascorbate. Spectrophotometric measurements did reveal a decrease in
      the rate of oxidation of ascorbate by Cu2+ ions in a solution preliminarily
      treated with magnetic fields.

PMID- 11969170
TI  - [Membrane potential before and after deep freezing of Escherichia coli in the
      presence of dimethyl sulfoxide and diethyl sulfoxide].
AB  - It was shown by the method of penetrating tetraphenylphosphonium cations that low
      temperature freezing (-196 degrees C) of Escherichia coli leads to a sharp
      decrease (from 198 to 85 mV) in membrane potential. Incubation of bacteria in a
      medium containing dimethyl sulfoxide and diethyl sulfoxide as cryoprotectors
      results in a reduction of the potential by 16 and 27 mV, respectively. It was
      also shown that diethyl sulfoxide is more effective in maintaining the membrane
      potential after freezing--thawing than dimethyl sulfoxide.

PMID- 11969171
TI  - [Autofluorescence of intact Equisetum arvense L. spores during their
      development].
AB  - The autofluorescence of horsetail Equisetum arvense spores excited with UV-light
      of 360-380 nm was studied by microspectrofluorimetry during their development
      from an individual cell to the formation of a multicellular thallus with the
      generative organs. The investigation involved the registration of the
      fluorescence spectra of individual intact developing cells and the measurement of
      the ratio of cell fluorescence intensities in the blue and red regions of the
      spectrum. Dry blue-fluorescing microspores showed the maxima at 460 and 530 nm
      and a small maximum at 680 nm. Thirty minutes after moistening in water, red
      fluorescing cells arose among blue-fluorescing microspores, indicating the onset
      of development. Red fluorescence with a maximum at 680 nm enhanced as cells put
      off their cover, which brightly fluoresced in the blue region of the spectrum
      with the main maximum at 460 nm. By estimating the ratio of autofluorescence
      intensities in the blue region of the spectrum to red lightening of microspores
      at the first stages of development up to 24 h (in particular, their first
      division, the formation of nonfluorescencing rhizoid, etc.), nonviable (only blue
      lightening) cells were distinguished from viable cells, in which red fluorescence
      began to prevail. After 25-40 days of development, the gametophyte fluorescing
      mainly at 680 nm formed male organs, antheridia, with blue-green-fluorescing
      spermatozoids. Then female generative organs archegonia with the egg cell
      appeared, which fluoresced blue, whereas the surrounding cells fluoresced red. It
      was supposed that the lightening in the blue and green regions of the spectrum is
      due to the presence of phenols, terpenoids, and azulenes, whereas the emission in
      the red region is associated with the presence of chlorophyll and azulenes. The
      observation of autofluorescence makes it possible to easily distinguish
      generative cells without additional staining.

PMID- 11969172
TI  - [Analysis of seasonal fluctuations in the Lotka-Volterra model].
AB  - A modification of the Lotka-Volterra model was proposed. The modification takes
      into account the factor of seasonal fluctuations in a "predator-prey" model. In
      this modification, interactions between species in summer are described by the
      Lotka-Volterra equations; in winter, individuals of both species extinct. This
      generalization makes the classic model unrough, which substantially extends the
      field of its application. The results of numerical simulation illustrate the
      statement formulated above.

PMID- 11969173
TI  - [Magnetically-guided anesthetics based on highly dispersed iron powders coated by
      polyacrylamide].
AB  - The effect of external magnetic field (direct and alternating) on the targeted
      delivery and distribution in body tissues of experimental animals of anesthetics
      (novocain, lidocaine, and trimecaine) immobilized on highly dispersed
      ferromagnetics with biocompatible coating was studied by the method of emission
      spectral analysis. The results are compared with the results obtained earlier on
      highly dispersed iron powders with dextran coating. The parameters for the
      powders with dextran coating are considerably lower than those for the magnetic
      carriers with the polyacrylamide coating.

PMID- 11969174
TI  - [Characteristics of activity of "fast" and "slow" Purkinje cells of the
      cerebellum].
AB  - In the guinea pig cerebellar cortex, three types of Purkinje cells were
      identified according to the properties of complex spikes: fast, intermediate, and
      slow cells. Fast Purkinje cells have following properties as compared with slow
      Purkinje cells: (i) salient components with short intervals in complex impulses
      (on the average, five components with a period of about 2 ms versus two
      components with a period of about 4 ms); (ii) a short duration of simple spikes
      (in the average, 2.13 +/- 0.53 ms versus 3.9 +/- 0.65 ms) and a quick restoration
      of their amplitude after preceding simple spikes (in the mean, 2.83 +/- 0.75 ms
      versus 11.0 +/- 2.82 ms); and (iii) a more pronounced rebound in the auto
      correlation histogram of simple spikes (3.09 +/- 2.12 versus 1.45 +/- 0.36) and a
      short-latency excitation of simple spikes after complex spikes (2.81 +/- 1.64
      versus 1.26 +/- 0.52). A decrease of interspike intervals in simple spike
      activity of all Purkinje cells was revealed (5.25 +/- 2.71 ms versus 9.71 +/-
      3.48 ms in activity fragments without complex spikes). It is supposed that the
      properties of complex spikes depend on the type of Purkinje cells and may be one
      of the basic factors determining the interactions between the inputs of climbing
      and parallel fibers in Purkinje cells.

PMID- 11969175
TI  - [Registration by dynamic phase microscopy of characteristic frequencies of phase
      height fluctuations of the myelin nerve fiber at rest and under stimulation].
AB  - The method of dynamic phase microscopy was used to study the dynamics of changes
      in the structure of paranodal and nodal regions of a myelin nerve fiber of brown
      frog Rana temporaria at rest and under stimulation. Regular structural changes
      with frequencies of 5.3 and 10.8 Hz in the nodal region of the myelin nerve fiber
      were detected. A rhythmic excitation leads to additional changes in the structure
      of the nodal region with a new frequency of 5.6 Hz. It is likely that the regular
      changes in the nodal region of the myelin nerve induced by rhythmic excitation
      are due to slow changes in the axolemma (changes in the mode of lateral diffusion
      of membrane phospholipids), induced by developing trace changes in the membrane
      potential of the axolemma. The fact that these changes do not occur in the
      paranodal region of the fibre may indicate either the localization of regular
      structural changes in the axolemma or the difficulties that arise during the
      registration of the useful signal in the vicinity of myelin by this method.

PMID- 11969176
TI  - [Mobile cardiac electrical center: a new concept and mathematical modeling].
AB  - A method for determination of the cardiac electric center on the basis of
      noninvasive multichannel measurements and multipole description of the
      cardioelectric potential is proposed. The method provides a more accurate and
      stable spatial location of the cardioelectric generator as compared to other
      methods (in particular, those based on minimization of the quadrupole potential).
      The position of the electric center is a useful characteristic for topical
      diagnosis of the electrophysiological state and function of the heart. Using
      mathematical models, the dependence of the position of the electric center,
      determined by the method presented, on the configuration and spatial position of
      the cardiogenerator is illustrated.

PMID- 11969177
TI  - [Changes in composition of cardiac myosin light chains in dilated cardiomyopathy:
      effect on functional properties].
AB  - A reduction (by 16-24%) in the amount of myosin regulatory light chains (LC2) in
      all heart sections of patients with dilated cardiomyopathy was found. The
      appearance of atrial essential light chains in ventricular myosin (up to 23%) not
      typical for this heart section in norm was also revealed. The decrease in LC2
      content leads to a considerable inhibition of actin-activated ATPase activity and
      a loss of Ca2+ sensitivity of reconstructed filaments of myosin isolated from
      atria and ventricles of patients with dilated cardiomyopathy. The hybridization
      of myosin molecules from heavy chains of pathological human left ventricular
      myosin and light chains of pig left ventricular myosin leads to an increase in
      actin-activated ATPase activity of myosin and its Ca2+ sensitivity to the control
      level. The data suggest strongly the contribution of LC2-deficit to the
      distortion of functional properties of myosin in dilated cardiomyopathy. In
      contrast, the appearance of atrial LC1 in ventricle in dilated cardiomyopathy is
      a factor improving these properties.

PMID- 11969178
TI  - [Composition of myosin light chains from the human myocardium: prospects for
      diagnosis of cardiac diseases].
AB  - New data on changes in the quantitative and qualitative composition of myosin
      light chains of human myocardium in various cardiac diseases were obtained. The
      results presented are of importance for creating a new diagnostic test for the
      onset of acute cardiac disease and a prognostic test of the development of
      chronic cardiac disease.

PMID- 11969179
TI  - [Analysis of ECG in ventricular fibrillation in man and animals based on chaos
      theory].
AB  - The methods of the chaos theory were used to estimate the degree of irregularity
      of ventricular fibrillation in human and experimental animals. To verify the
      hypothesis that the degree of chaos depends on the species of the living
      organisms, the parameters characterizing the degrees of irregularity of
      ventricular fibrillation were estimated and compared. The comparative analysis
      was performed using 32 fragments of electrocardiographic records from five
      patients with sudden ventricular fibrillation bouts and 215 episodes of induced
      fibrillation in 17 animals. It was shown that fibrillation in human and animals
      has a different degree of regularity and different values of the chaotic
      component. The highest values of chaos were recorded in dogs, the lowest degree
      of chaos was observed in human. Rabbits and rats are intermediate, between dogs
      and humans. The fractuality of the structure-function organization of myocardium
      is discussed.

PMID- 11969180
TI  - [Immunomodulating effect of electromagnetic waves on production of tumor necrosis
      factor in mice with various rates of neoplasm growth].
AB  - The effects of low-density centimeter waves (8.15-18 GHz, 1 microW/cm2, 1 h daily
      for 14 days; MW) on tumor necrosis factor production in macrophages of mice with
      different growth rate of a cancer solid model produced after hypodermic injection
      of Ehrlich carcinoma ascites cells into hind legs were studied. After
      irradiation, an increase in the concentration of tumor necrosis factor in
      immunocompetent cells of healthy and, specially, of tumor-bearing animals was
      observed; and the effect of stimulation was higher upon exposure of mice carrying
      rapidly growing tumors. We suggest that the significant immunomodulating effect
      of low-density microwaves can be utilized for tumor growth suppression.

PMID- 11969182
TI  - Evaluation of certain mycotoxins in food. Fifty-sixth report of the Joint FAO/WHO
      Expert Committee on Food Additives.
AB  - This report presents the conclusions of a Joint FAO/WHO Expert Committee convened
      to assess the risks associated with the consumption of food contaminated with
      certain mycotoxins. The first part of the report contains a general discussion of
      the principles for evaluating mycotoxins in food, including those concerning
      analytical methods, sampling, data on food consumption and dietary intake, and
      prevention and control. The second part provides a summary of the Committee's
      evaluations of toxicological data on specific mycotoxins, including aflatoxin M1,
      fumonisins B1, B2 and B3, ochratoxin A, deoxynivalenol, and T-2 and HT-2 toxins.

PMID- 11969183
TI  - A review of fluorescence methods for assessing labile iron in cells and
      biological fluids.
AB  - A variety of biochemical, pharmacological, and toxicological properties have been
      attributed to labile forms of iron that are associated with cells or with
      biological fluids. Unlike the major fraction of bioiron which is protein bound,
      the labile bioiron is chelatable and therefore amenable for detection by metal
      sensing devices that are coupled to chelation moieties. The present review deals
      with the detection of various labile forms of iron present in living cells and in
      fluids of biological interest, in health and disease. The main focus of the
      review is on the design and application of fluorescent probes as analytical tools
      for assessing labile iron and iron transport mechanisms and the efficiency of
      iron chelators in solution and in cellular systems.

PMID- 11969184
TI  - Development of an ultrasensitive noncompetitive hybridization-ligation enzyme
      linked immunosorbent assay for the determination of phosphorothioate
      oligodeoxynucleotide in plasma.
AB  - An ultrasensitive noncompetitive hybridization-ligation heterogeneous enzyme
      linked immunosorbent assay was developed for the quantitation of antisense
      phosphorothioate oligodeoxynucleotides in plasma using a 96-well plate format.
      The principle of the assay is based on heterogeneous noncompetitive binding of
      the analyte to a template probe, followed by addition of signal probe via
      ligation and detection using a fluorescence microtiter plate reader. The result
      showed no significant interference noted from untreated human plasma. In
      addition, the method is selective for the specific sequence tested (ISIS 2302)
      and cross-reactivity toward the 3'-metabolites is minimal (< 0.22%). A linear
      range of 0.05 to 2 nM (r > 0.99) was obtained in human plasma for ISIS 2302.
      Intraday and interday accuracy for the method was found to be within 80-120% of
      actual value. Intraday and interday precision has a percentage coefficient of
      variation less than 20%. The lower limit of quantitation of the method was 0.05
      nM (0.05 pmol/ml) with 100 microL plasma or an absolute amount of 5 fmol. In
      summary, the assay was demonstrated to be specific, accurate, precise, and
      sensitive for the quantitation of ISIS 2302 in human plasma and was applied to
      the analysis of plasma samples in pharmacokinetic studies.

PMID- 11969185
TI  - Determination of glutamate-cysteine ligase (gamma-glutamylcysteine synthetase)
      activity by high-performance liquid chromatography and electrochemical detection.
AB  - The tripeptide glutathione (gamma-glutamylcysteinylglycine; GSH) is the
      predominant low molecular mass thiol in cells. The function of GSH is of
      considerable interest, with the molecule being implicated in numerous cellular
      processes in addition to being a major cellular antioxidant. The enzyme glutamate
      cysteine ligase (GCL) is the rate-limiting step in GSH synthesis. The GCL assay
      described here is based on high-performance liquid chromatography and exploits
      the electrochemically active nature of gamma-glutamylcysteine (gamma-GC), the
      product of GCL activity. This method allows for the direct detection of gamma-GC
      rather than relying on derivatization of the molecule or linked assays. The
      sensitivity of the assay is sufficient to allow for the measurement of GCL
      activity in cultured cells. The specific activity of GCL in rat primary culture
      astrocytes was 9.7 +/- 1.7 nmol gamma-GC synthesized/min/mg protein.

PMID- 11969186
TI  - Silver staining of proteins on electroblotting membranes and intensification of
      silver staining of proteins separated by polyacrylamide gel electrophoresis.
AB  - A fast and convenient method for silver staining of proteins on electroblotting
      membranes was developed based on Gallyas' histochemical intensifier and applied
      to human endothelial cell proteins separated by one- and two-dimensional
      electrophoresis and electroblotted to polyvinyl difluoride membranes. The method
      allowed detection of proteins on membranes with a sensitivity equal to the
      sensitivity of the most sensitive silver-staining protocols for electrophoresis
      gels. Also, the method was compatible with preceding immunostaining on the same
      membrane. Furthermore, an intensifying method for proteins in silver-stained SDS
      PAGE gels was developed based on Gallyas' histochemical intensifier. This method
      was applied to proteins separated by one- and two-dimensional gel electrophoresis
      and visualized by one of several silver-staining methods. Maximal intensification
      was achieved for the less sensitive but fast acidic silver-staining protocols,
      but even for the very sensitive alkaline protocols a significant increase in
      signal to noise ratio was obtained. In particular, negatively stained or
      invisible proteins on the silver-stained gels were found to be visualized by the
      Gallyas stain. Proteins from silver-stained and Gallyas-stained gels were
      identified by mass spectrometry, and the intensification procedure was fully
      compatible with mass spectrometry.

PMID- 11969187
TI  - Perchloric acid enhances sensitivity and reproducibility of the ferric-xylenol
      orange peroxide assay.
AB  - The ferrous oxidation in xylenol orange (FOX) assay for hydroperoxides suffers
      from very narrow pH optimum in the range 1.7-1.8. Most published protocols
      recommend 25 mM sulfuric acid as the solvent, but this in practice does not
      ensure the maintenance of correct pH in the presence of materials such as samples
      of biological origin. Substitution of perchloric for the sulfuric acid resulted
      in a lowering of the optimum pH of the assay to 1.1, a decreased dependence of
      the absorbance of the ferric-xylenol orange complex on acid concentration and
      decreased sensitivity to added compounds. Molar absorption coefficients of
      hydrogen peroxide, cumene, and butyl hydroperoxides and of hydroperoxide groups
      generated in oxidized protein and lipids were determined and found to be higher
      than in sulfuric acid. The optimum concentration of perchloric acid proved to be
      110 mM. The new assay was designated as PCA-FOX, to distinguish it from the FOX
      methods based on sulfuric acid.

PMID- 11969188
TI  - Multidimensional differential display via ion-pair reversed-phase denaturing high
      performance liquid chromatography.
AB  - Experimental approaches are now available for the analysis of whole transcriptome
      expression in cells and tissues. Since the introduction of such methods for the
      investigation of differences in mRNA populations, they have been applied
      successfully to many areas of biology and medicine including development,
      differentiation, physiology, pharmacology, and carcinogenesis. Here we describe
      an improved and automated approach based on the differential mRNA display method
      developed by Liang and Pardee (P. Liang and A. B. Pardee, 1992, Science 257, 967
      971). We report the use of ion-pair reversed-phase denaturing high-performance
      liquid chromatography (IP RP DHPLC), for the first time, to produce a
      "fingerprint," after amplification of the cDNA corresponding to the mRNA
      populations, from two or more of the samples that are to be compared. By
      overlaying the chromatograms produced from the amplification of different samples
      derived from the same set of oligodeoxynucleotide primers, those genes that are
      differentially expressed can be selected and subsequently cloned and sequenced
      rapidly to establish a profile of differentially expressed genes. In addition,
      validation of the data obtained is readily achieved by this method using IP RP
      DHPLC and quantitative RT-PCR. In this study total RNA was prepared from NTERA2
      cells before and after differentiation induced by retinoic acid and was reverse
      transcribed into cDNA prior to amplification to produce fluorescently tagged
      products. This methodology facilitates multiple rounds of interrogation of RT-PCR
      products and we tentatively refer to this approach as Multidimensional
      Differential Display.

PMID- 11969189
TI  - An ATPase assay using scintillation proximity beads for high-throughput screening
      or kinetic analysis.
AB  - A new procedure for measuring ATPase activity in which gamma-(33)P-labeled
      inorganic orthophoshate is detected by addition of ammonium molybdate followed by
      selective adsorption of the resulting phosphomolybdate to scintillation proximity
      beads in the presence of cesium chloride is described. This method is shown to
      give accurate and reproducible results over a wide range of detection conditions
      and product concentrations. It requires no separation or filtration steps and is
      highly compatible with automated high-throughput screening. Rates of hydrolysis
      are easily and accurately determined over a wide range, and thus the method is
      useful for kinetic studies also. We show that this scintillation proximity assay
      is useful for the study of the E1 helicase of human papillomavirus, but it is a
      general procedure which could also be applied to any ATPase or other nucleotide
      triphosphate-hydrolyzing enzyme or any other enzyme which generates
      orthophosphate as a reaction product.

PMID- 11969190
TI  - Development of a homogeneous, fluorescence resonance energy transfer-based in
      vitro recruitment assay for peroxisome proliferator-activated receptor delta via
      selection of active LXXLL coactivator peptides.
AB  - The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors
      activated by fatty acids and their metabolites. The PPARdelta subtype is believed
      to be involved in lipoprotein regulation and may have a role in reverse
      cholesterol transport. While the range of biological roles of PPARdelta still
      remains unclear, it is of therapeutic interest in cardiovascular diseases. Here
      we report a homogeneous in vitro assay for studying ligand activation of
      PPARdelta. We surveyed a panel of peptides containing the LXXLL motifs derived
      from coactivator protein sequences. Peptides with the best response were used to
      develop a sensitive and homogeneous recruitment assay for PPARdelta. The
      optimized assay has a signal-to-background ratio of about 8:1 and an assay
      quality parameter Z'-factor value of 0.8. The assay signal generated is stable
      for hours to even overnight. This simple recruitment assay can provide agonist
      and/or antagonist information that cannot be assessed by receptor-binding assay,
      and can be used for characterization and screening of ligands that modulate the
      activation of PPARdelta.

PMID- 11969191
TI  - An analytical and structural database provides a strategy for sequencing O
      glycans from microgram quantities of glycoproteins.
AB  - A sensitive, rapid, quantitative strategy has been developed for O-glycan
      analysis. A structural database has been constructed that currently contains
      analytical parameters for more than 50 glycans, enabling identification of O
      glycans at the subpicomole level. The database contains the structure, molecular
      weight, and both normal and reversed-phase HPLC elution positions for each
      glycan. These observed parameters reflect the mass, three-dimensional shape, and
      hydrophobicity of the glycans and, therefore, provide information relating to
      linkage and arm specificity as well as monosaccharide composition. Initially the
      database was constructed by analyzing glycans released by mild hydrazinolysis
      from bovine serum fetuin, synthetic glycopeptides, human glycophorin A, and serum
      IgA1. The structures of the fluorescently labeled sugars were determined from a
      combination of HPLC data, mass spectrometric composition and mass fragmentation
      data, and exoglycosidase digestions. This approach was then applied to human
      neutrophil gelatinase B and secretory IgA, where 18 and 25 O-glycans were
      identified, respectively, and the parameters of these glycans were added to the
      database. This approach provides a basis for the analysis of subpicomole
      quantities of O-glycans from normal levels of natural glycoproteins.

PMID- 11969192
TI  - Recovery of intact 2-aminobenzamide-labeled O-glycans released from glycoproteins
      by hydrazinolysis.
AB  - The initial step in quantitative analysis of O-linked glycans of glycoproteins is
      to release them in high yield, nonselectively, unmodified, and with a free
      reducing terminus. In contrast to other techniques, hydrazinolysis can meet these
      criteria. However, when analyzing pools of O-linked glycans as described in the
      accompanying article by L. Royle et al. (2002, Anal. Biochem. 304), some peeling
      of the glycans was observed. Critical steps in the sample preparation and glycan
      recovery were therefore evaluated by analyzing and identifying both intact O
      glycans and degraded products. Synthetic O-glycopeptides were characterized by
      mass spectrometry. Released glycans were identical to those on the glycopeptide.
      O-Linked glycans from a range of glycoproteins of increasing complexity, namely,
      bovine serum fetuin, glycophorin A, and previously uncharacterized glycopeptides
      isolated from human salivary mucin Muc5B, were also analyzed. Quantitative
      analysis of the glycan profile confirmed that there was <2% peeling of O-glycans
      released by hydrazinolysis conditions of 60 degrees C for 6 h, and recovered
      using the optimised procedure now described. This demonstrated that O-glycans can
      be prepared by hydrazinolysis without degradation and, as part of an analytical
      strategy, makes the analysis of O-glycans attached to low-microgram levels of
      naturally occurring glycoproteins feasible.

PMID- 11969193
TI  - Method for the simultaneous determination of retinol and beta-carotene
      concentrations in human tissues and plasma.
AB  - To understand differential tissue distribution of retinoids and carotenoids, as
      it might influence biological processes in humans, we developed and demonstrated
      a method for measuring them in selected human tissues. The method includes
      internal standards and a secondary reference standard to eliminate the need for
      external standard calibration and to minimize sample-handling errors. Tissues
      were digested (saponified) in ethanolic KOH. Retinol and beta-carotene were
      extracted with organic solvent containing internal standards. Analytes were
      separated using isocratic liquid chromatography and quantified at 325 nm for
      retinol and 450 nm for beta-carotene. Plasma was analyzed in a similar way but
      without saponification. Retinal-O-ethyloxime and beta-apo-12'-carotenal-O-t
      butyloxime served as internal standards. Plasma, breast, and fat from breast
      surgery patients and colon, liver, muscle, and fat from colon surgery patients
      were analyzed. Within-day relative standard deviations (RSDs) for plasma were
      <0.04 for beta-carotene and <0.03 for retinol, between-day RSDs were <0.05 for
      beta-carotene and <0.04 for retinol. Saponification ensured complete extraction
      of retinol and beta-carotene and removal of triglycerides that "foul"
      chromatographic columns. It seems retinol and beta-carotene concentrations in
      tissues and blood of cancer patients are the same or higher than those in
      corresponding tissues of patients without these cancers.

PMID- 11969194
TI  - PolC-type polymerase III of Streptococcus pyogenes and its use in screening for
      chemical inhibitors.
AB  - The polC gene from Streptococcus pyogenes (S. pyogenes, strain SF370) has been
      cloned and expressed in Escherichia coli (E. coli) as a fusion protein containing
      an N-terminal histidine tag. The purified recombinant enzyme showed an apparent
      molecular mass of 160 kDa on SDS-PAGE and a specific activity of 3.5 nmol/min/mg
      when assayed in the presence of calf thymus DNA and the four deoxyribonucleoside
      triphosphates. This activity was inhibited by TMAU, a specific inhibitor of PolC.
      To facilitate kinetic studies, and high-throughput assays, a double-stranded
      oligo DNA primer/template was used as a substrate. The minimum requirement for
      the length of the substrate was a 20-base oligo primer annealed to a 35-base
      template. PolC activity was detected either by a filter-binding format or by a
      novel homogeneous scintillation proximity assay (SPA). Sensitivity to inhibition
      by anilinouracil analogs was improved by incorporating three deoxycytidines in
      the template strand as the first 3 bases to be copied by the polymerase.
      Inhibition of PolC activity by trimethyleneanilinouracil by the filtration and
      SPA methods gave comparable results, but the SPA assay uses less radioactive
      label, is less time-consuming, and is amenable to high-throughput formatting.

PMID- 11969195
TI  - A positive control for the green fluorescent protein-based one-hybrid system.
AB  - The yeast one-hybrid system (1H-system) is applied to studies of transcription
      linked DNA-protein interactions under in vivo conditions detected by reporter
      gene expression. By use of a variant of green fluorescent protein (GFP) as a
      reporter, the new 1H-system generation represents a time- and work-saving
      alternative to the established HIS3/lacZ-based form. However, hitherto, a
      positive control proving the functionality of the system has been missing. We
      designed a corresponding control vector combination by subcloning mouse p53 cDNA
      and its binding sequence and, to get the system working, modified the distance
      between cloning site and reporter gene promoter in the reporter vector by site
      directed mutagenesis. This provides, for the first time, a positive control
      vector combination for the GFP 1H-system, crucial for its employment in any DNA
      protein interaction studies.

PMID- 11969196
TI  - beta-naphthoflavone, an inducer of xenobiotic metabolizing enzymes, inhibits
      firefly luciferase activity.

PMID- 11969197
TI  - Analysis of neutral saccharides in human milk derivatized with 2-aminoacridone by
      capillary electrophoresis with laser-induced fluorescence detection.

PMID- 11969198
TI  - Casein zymography of calpains using a 4-(2-hydroxyethyl)-1
      piperazineethanesulfonic acid-imidazole buffer.

PMID- 11969199
TI  - Enhancement of in situ hybridization signals in Caenorhabditis elegans by
      tyramide signal amplification.

PMID- 11969200
TI  - Enzymatic chemiluminescence assay for inorganic pyrophosphate.

PMID- 11969201
TI  - Konrad Bloch--a pioneer in cholesterol and fatty acid biosynthesis.

PMID- 11969203
TI  - Sterol biosynthesis: the early days.

PMID- 11969204
TI  - Membrane-bound enzymes of cholesterol synthesis from lanosterol.

PMID- 11969205
TI  - Cholesterol, hydroxycholesterols, and bile acids.
AB  - Although a variety of oxidation products of cholesterol occur in vitro, enzyme
      catalyzed oxidations can occur at only 5 sites on the cholesterol molecule:
      C7alpha, C22R, C24S, C25, and C27. The genes coding for the synthesis of these
      enzymes were cloned, the tissue expressions of the mRNAs were identified, and the
      enzymes were characterized. The biologic properties of the hydroxycholesterol
      molecules that are initially generated and their metabolites are under study.
      Downregulation of cholesterol synthesis via the SREBP/SCAP regulatory pathway is
      common to the initial hydroxycholesterols, but more variations exist with respect
      to these intermediates functioning as ligands for the nuclear receptor LXRalpha.
      Because this receptor regulates the expression of cholesterol 7alpha-hydroxylase
      and ABC transporter proteins, hydroxycholesterols and their intermediate steroid
      metabolites modulate a number of biologic processes. Metabolism of 22S
      hydroxycholesterol to steroid hormones differs from that of the other
      hydroxycholesterols which form mostly steroid acidic products, otherwise known as
      bile acids. In vivo estimates of their production rates in intact humans indicate
      that 24S and 25-hydroxycholesterol account for no more than 7% of total bile acid
      production per day. Current evidence indicates that cholesterol 7alpha
      hydroxycholesterol generated in the liver is the major source of bile acids in
      older adults. It is also known that the cholesterol 27-hydroxylation pathway is
      the only one expressed in fetal and neonatal life. Precisely when the proportions
      contributed by these two metabolic pathways to bile acid synthesis begin to shift
      and the role of the cholesterol 27-hydroxylase pathway in reverse cholesterol
      transport mandate further study.

PMID- 11969206
TI  - Forty years of bacterial fatty acid synthesis.

PMID- 11969207
TI  - Remembering Konrad Bloch.

PMID- 11969208
TI  - Direct hydration of 3-octynoyl-CoA by crotonase: a missing link in Konrad Bloch's
      enzymatic studies with 3-alkynoyl thioesters.

PMID- 11969209
TI  - My time in Professor Konrad Bloch's Laboratory.

PMID- 11969210
TI  - My years with Konrad, a memoir.

PMID- 11969211
TI  - My hand was on the doorknob to leave.

PMID- 11969212
TI  - Insects, oxygen, and iron.
AB  - Konrad Bloch developed an interest in insects because they are unable to make
      sterols, and in yeast because these cells need oxygen to make sterols and
      unsaturated fatty acids. Insects, like all other organisms, must deal with the
      toxic effects of oxygen in the presence of iron, which itself is a vital
      nutrient. They do so by making proteins with high affinity for ferric or ferrous
      ions. Two such proteins are transferrins and ferritins. Insects produce both of
      these proteins, but use them in different ways from most other organisms. Insect
      transferrins appear to be involved in innate immunity, perhaps by sequestering
      ferric ions to prevent pathogens and parasites from utilizing them. Insect
      ferritins, unlike those of any other group of organisms, are exported into the
      extracellular space (hemolymph). They may be involved in iron transport and/or
      protection against iron overload in the diet.

PMID- 11969213
TI  - Memories of a graduate student.

PMID- 11969214
TI  - From unsaturated fatty acids to lipid polymorphism.

PMID- 11969215
TI  - Memories and outcomes of my postdoctoral work with Konrad Bloch.

PMID- 11969216
TI  - Yeast hydroxy fatty acids and fungal polyketides: lessons learned from the Konrad
      Bloch laboratory.

PMID- 11969217
TI  - My Bloch years: 1961-1963 and beyond.

PMID- 11969218
TI  - A model scientist.

PMID- 11969219
TI  - Remembrances of Konrad Emil Bloch--molecular biology in a lipid lab in the 1960s:
      studies on amino acid activation for protein synthesis.

PMID- 11969220
TI  - My life in Konrad's Lab.

PMID- 11969221
TI  - The Euglena mystery: some thoughts on aerobic desaturation.

PMID- 11969222
TI  - Membrane-bound lecithin-retinol acyltransferase.

PMID- 11969224
TI  - Lipids and life.

PMID- 11969223
TI  - Variations on the theme "Tier-chemie ist Schmier-chemie".

PMID- 11969225
TI  - The road to squalene synthase.

PMID- 11969226
TI  - Konrad Bloch, evolution, and the RNA world.

PMID- 11969227
TI  - A stimulating factor for fatty acid biosynthesis--research with Konrad Bloch:
      mentor and friend.

PMID- 11969228
TI  - Lipids and me.

PMID- 11969229
TI  - The first step of oxygenation in cholesterol biosynthesis.

PMID- 11969230
TI  - Sterols and acylated proteins in mycoplasmas.

PMID- 11969231
TI  - Supernatant protein relevant to the activity of membrane-bound enzymes: studies
      on lathosterol 5-desaturase.

PMID- 11969232
TI  - Molecular and genetic defects in colorectal tumorigenesis.
AB  - Colorectal cancers, whether sporadic or hereditary, are caused by a defined set
      of molecular events. There are at least two different pathogenetic pathways for
      colorectal cancer: the chromosomal instability pathway and the microsatellite
      instability pathway; the two major inherited syndromes, familial adenomatous
      polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), are
      examples of these two mechanisms. These different pathways, however, converge on
      common pathological entities that have crucial functions in the regulation of
      normal crypt homeostasis. Preventive strategies aimed at reversing these changes,
      or therapeutic interventions targeting cell populations with these alterations,
      should be most efficacious. Genetic testing for inherited syndromes is now
      available and allows appropriate management of these disorders. Further insight
      into colorectal tumorigenesis pathways can lead to the development of useful
      prognostic indicators and target preventive and therapeutic strategies in the
      management of colorectal cancer.

PMID- 11969233
TI  - Epidemiology and screening of colorectal cancer.
AB  - Knowledge of the descriptive epidemiology of colorectal cancer is essential to a
      better understanding of the aetiology of the disease and the development of
      screening strategies. Considerable research efforts have been launched over the
      last 15 years to evaluate the ability of screening tests to decrease the
      incidence and mortality of colorectal cancer. This chapter provides a worldwide
      update of the incidence of colorectal cancer and reviews the evidence for
      screening for colorectal cancer based on published studies.

PMID- 11969234
TI  - The role of nutrition and chemoprevention in colorectal cancer: from observations
      to expectations.
AB  - During the last 20 years the role of aspirin and other non-steroidal anti
      inflammatory drugs (NSAIDs) in reducing the risk of colorectal cancer was shown
      in more than 100 animal studies. Support derives from 23 of 25 epidemiological
      studies confirming this protective effect. The COX-2 specific inhibitors and the
      selective apoptotic anti-neoplastic drugs offer the benefit of cancer protection
      without the gastrointestinal toxicity that was reported for the 'old' drugs. The
      presence of multiple molecular targets offers the potential for combination. The
      pivotal question in the puzzle of NSAID chemopreventive treatment should not be
      'if' but 'how'. The concept that different food components may initiate or
      prevent cancer was illustrated by different epidemiological studies and animal
      models. Yet the chemical and biological complexity of the food, the difficulty in
      measuring habitual diets and the unavoidable changes in food constituents
      following a specific change in diet all contribute to this complexity.

PMID- 11969235
TI  - Virtual colonoscopy.
AB  - Computerized tomographic colonography (CT colonography) is a new, non-invasive
      technique that has been developed over the last few years; it looks at the large
      bowel in detail. In this chapter we look at how the examination is performed and
      we consider how the images are displayed. We describe the normal features of the
      colon, as seen using this technique, as well as the features of common
      pathological conditions. We will discuss screening for colorectal cancer and the
      performance of CT colonography; we compare the latter with other procedures
      currently employed in the screening and diagnosis of colorectal pathology. We
      consider the difficulties in interpreting these CT colonographic images and look
      at ways to overcome such difficulties. Finally we discuss future developments of
      this exciting, new technique.

PMID- 11969236
TI  - Positron emission tomography in colorectal cancer.
AB  - Positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) is
      increasingly used in the diagnostic management of colorectal cancer patients. It
      provides a highly sensitive and specific diagnosis which is entirely based upon
      alterations of the glucose metabolism found in malignant tissues. The information
      provided by FDG-PET is independent of the underlying structural characteristics
      of the lesions and, therefore, it is essentially complementary to the available
      structural imaging modalities such as CT, MRI and (endoscopic) ultrasound.
      Several studies have now been performed on the use of FDG-PET in colorectal
      adenocarcinoma for primary pre-operative staging, for diagnosis and (re)staging
      of recurrent disease, for localization and staging of occult recurrent disease,
      and for the assessment of the metabolic effects of chemotherapy and radiotherapy.
      This chapter aims to clarify some fundamental issues of both detection device and
      radiotracer, the proven indications for FDG-PET, the strength and limitations of
      the technique, and how its implementation would affect patient management.

PMID- 11969237
TI  - Surgery for colon and rectal cancer.
AB  - Radical surgery remains the only potentially curative treatment for colorectal
      cancer. Major changes in the principles of rectal cancer resection have been
      recently described (total mesorectum excision) whereas there have been few
      changes in the principles of colonic cancer resection. This chapter presents
      surgical procedures for curative treatment of colorectal cancer in both the
      elective and emergency settings.

PMID- 11969239
TI  - Adjuvant chemotherapy for colon cancer.
AB  - Colorectal cancer is one of the most frequent cancers in the world, especially in
      occidental countries. The primary curative therapy is surgical resection of the
      tumour. Within the last 15 years, appropriately powered prospective randomized
      trials have demonstrated that adjuvant post-operative chemotherapy should be the
      standard treatment for stage III cancers (node-positive disease). 5
      Fluorouracil(5FU)/levamisole was used in the early 1990s but has now been
      replaced by 5FU/leucovorin. The recommended duration of treatment is 6 months.
      Combining levamisole with 5FU/leucovorin does not improve efficacy. In patients
      with stage II colon cancer it is still unclear whether adjuvant chemotherapy is
      effective. In an attempt to define groups of stage II cases that may benefit from
      adjuvant chemotherapy, considerable efforts have been made to determine molecular
      genetic factors (tumour-ploidy and mutations or alterations in oncogenes and
      tumour-suppressor genes). Regional therapy (particularly portal vein infusion) is
      one of the other therapeutic strategies still considered to be investigational.
      Current clinical trials are evaluating the role of non-fluorinated pyrimidine
      agents in an adjuvant setting.

PMID- 11969238
TI  - Radiation plus chemotherapy as adjuvant therapy for rectal cancer.
AB  - The most common neo-adjuvant therapy for rectal cancer is chemotherapy and
      concurrent radiation therapy. In general, it is delivered pre-operatively for
      patients with clinical evidence of T(3-4) disease or post-operatively in patients
      who have undergone surgery and have T(3) and/or N(1-2) disease. This chapter
      reviews the rationale and results for neo-adjuvant therapy, the selection process
      for pre-operative versus post-operative treatment, and new approaches and
      controversies.

PMID- 11969240
TI  - Resection and local therapy for liver metastases.
AB  - In 30-50% of patients the liver is a preferred site of distant disease for many
      malignant tumours. Due to the high incidence, most of the available data relate
      to metastases arising from colorectal primaries. Surgical resection is at present
      the only treatment offering potential cure. The achievable 5-year survival rate
      is 30%. However, only 10-15% of patients with colorectal liver metastases can
      undergo potentially curative liver resection. Therefore, accurate staging is an
      important prerequisite in selecting patients who would benefit from surgery.
      Recurrence of hepatic metastases after potentially curative resection occurs in
      up to 60% of the cases. Results demonstrate that re-resection of liver metastases
      can provide long-term survival rates in a carefully selected group of patients
      without extrahepatic disease. Because of the high rate of recurrences following
      an apparently curative resection several authors investigated the use of adjuvant
      chemotherapy (systemic, intraportal, and hepatic arterial infusion). Until
      recently none had shown effectiveness. Pre-operative chemotherapy seems to be a
      promising approach in patients with liver metastases initially considered
      unsuitable for radical surgery. Recently, neoadjuvant chemotherapy has been
      proposed as an alternative approach to conventional surgery as initial management
      with the aim of improving the results in resectable liver metastases.
      Interventional strategies (ethanol injection, cryosurgery, laser-induced
      thermotherapy, radio-frequency ablation) and combined modalities
      (surgical/interventional) are additive methods which may help to improve
      treatment results in the future.

PMID- 11969241
TI  - The treatment of advanced colorectal cancer: where are we now and where do we go?
AB  - The treatment of patients with metastatic colorectal cancer has changed
      dramatically over recent years. The more optimal use of 5-fluorouracil (5-FU) in
      association with folinic acid (FA), the development of new drugs such as
      irinotecan and oxaliplatin and of the oral fluoropyrimidines, capecitabine and
      UFT, have contributed to increased therapeutic options and to the improved
      outcome of patients with metastatic colorectal cancer. It is shown that
      combination therapy with 5-FU/FA and irinotecan or oxaliplatin is more active
      than 5-FU/FA in the first-line treatment of advanced colorectal cancer.
      Irinotecan and oxaliplatin are also active in the second-line treatment of
      colorectal cancer. The oral fluoropyrimidines seem to have an activity comparable
      to that of intravenous 5-FU/FA in the first-line treatment of metastatic
      colorectal cancer. New agents acting on novel targets are under development:
      epidermal growth factor inhibitors, vascular endothelial growth inhibitors, COX-2
      inhibitors and farnesyl transferase inhibitors might play a role in the future in
      the treatment of colon cancer.

PMID- 11969242
TI  - Molecular markers in prognosis of colorectal cancer and prediction of response to
      treatment.
AB  - Colorectal cancer is the third most common human malignancy. Direct observation
      and biopsy sampling by colonoscopy have provided unique opportunities to study
      the natural history of the disease. As a consequence, advances in the
      understanding of colorectal cancer pathogenesis have evolved more rapidly than
      with most other solid tumours. Numerous molecular events arising during the
      development of colorectal cancer have been sorted out over the past two decades.
      Despite these advances, predicting outcome and response to therapy is still a
      major challenge in the management of patients with colorectal cancer. Molecular
      and biochemical markers of colorectal cancer are greatly needed for diagnosis and
      prognosis as well as for the selection and monitoring of treatments. The purpose
      of this chapter is to provide a critical assessment of the usefulness of markers
      in the prognosis and prediction of response to treatment in colorectal cancer.

PMID- 11969245
TI  - Neurocalcin-alpha immunoreactivity in the enteric nervous system of young and
      aged rats.
AB  - The distribution of the calcium binding protein neurocalcin a has been examined
      in the enteric nervous system of young adult (3 months) and aged (24+ months)
      male rats by immunofluorescence. Neurocalcin-immunoreactive (NC-ir) neurons were
      observed in the submucous and myenteric plexuses throughout the gastrointestinal
      tract from the oesophagus to the distal large intestine. NC-ir nerve terminals
      were also seen on NC-ir and NC-negative neurons. Semiquantitative estimates
      revealed fewer NC-ir neurons in the submucous plexus than in the myenteric
      plexus. The greatest occurrence of NC-ir neurons was in the small and large
      intestine. NC-ir axons were seen in the mucosa and also in between the ganglia of
      the myenteric plexus. In the aged rats, there were no discernible changes in the
      numbers of NC-ir neurons in th e oesophagus and stomach, with an increase in the
      pylorus and slight decreases in the small and large intestines. No decrease in NC
      ir was observed in the distal large intestine. NC-ir neurons never contained
      lipofuscin age pigment and many enteric neuro ns devoid of NC-ir contained age
      pigment. Like other previously investigated calcium-binding proteins in enteric
      neurons, the distribution of NC shows much variability from one part of the
      intestine to another. The observed slight decreases in the number of NC-ir
      enteric neurons in aged rats may compromise the regulation of calcium in these
      neurons.

PMID- 11969246
TI  - Visualization of inositol 1,4,5-trisphosphate receptor type III with green
      fluorescent protein in living cells.
AB  - Inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular Ca2+ channel
      that releases Ca2+ into the cytosol and its subcellular distribution is believed
      to have significant effects on Ca2+ signalling. We constructed a plasmid vector
      containing full-length rat type 3 IP3R linked to GFP (GFP-IP3R) for expression in
      mammalian cells. Western blot analyses revealed that the expressed fusion protein
      contained both GFP and full-length type 3 IP3R. Fluorescence confocal microscopy
      showed that the fluorescence of GFP-IP3R3 was distributed to reticular network
      structures, even after cell permeabilization with saponin. We further visualized
      intracellular membranes with DiOC6, a vital fluorescent marker for intracellular
      membranes, and provide evidence that the distribution of GFP-IP3R3 overlaps with
      the distribution of the endoplasmic reticulum. Our results indicate that GFP
      IP3R3 can be used to visualize IP3R in living cells, and pave the way for
      subsequent mutational and functional studies.

PMID- 11969247
TI  - Correlation between electrical activity and intracellular Ca2+ oscillations in
      GH3 rat anterior pituitary cells.
AB  - Simultaneous measurements of electrical activity and intracellular Ca(2+) levels
      were performed in perforated-patch current-clamped individual GH3 cells. Both in
      cells showing brief (<100 ms) and long action potentials (APs), we found a good
      correlation between the averaged intracellular Ca2+ concentration ([Ca2+]i) and
      AP frequency, but not between the mean [Ca2+]i and AP duration. Nevertheless, the
      magnitude of spontaneous Ca2+ oscillations was highly dependent on the size and
      duration of the APs. The decay of the Ca2+ transients was not slowed when the
      size of the oscillations was varied either spontaneously or after elongation of
      the AP with the K+ channel blocker tetraethyl ammonium. Furthermore, the recovery
      from Ca2+ loads similar to those induced by the APs was slightly retarded after
      treatment of the cells with intracellular store Ca2+-ATPase inhibitors. Among
      previous results showing that caffeine-induced [Ca2+]i increases are secondary to
      electrical activity enhancements in GH3 cells, these data indicate that the Ca2+
      entry triggered via APs is the primary determinant of the [Ca2+]i variations, and
      that Ca2+-induced Ca2+ release has a minor contribution to Ca2+ oscillations
      recorded during spontaneous activity. They also point to modulation of electrical
      activity patterns as a crucial factor regulating spontaneous [Ca2+]i signalling,
      and hence pituitary cell functions in response to physiological secretagogues.

PMID- 11969248
TI  - Red blood cells of the lizards Ameiva ameiva (Squamata, Teiidae) display multiple
      mechanisms to control cytosolic calcium.
AB  - We have previously reported that lizard red blood cells control their cytosolic
      calcium concentration by sequestering calcium ions in pools, which could be
      discharged by thapsigargin, by the Na+/H+ ionophore, monensin, by the K+/H+
      ionophore, nigericin and by the proton pump inhibitor, bafilomycin A1 [1]. We
      have now demonstrated, with the aid of confocal microscopy, the presence in these
      cells of organelles, which accumulate the dye acridine orange and are thus by
      inference the sites of proton pools. We have found, moreover, that monensin,
      nigericin and bafilomycin all act to discharge these pools. We further show that
      calcium release ensues when the calcium ionophore, ionomycin, is added after
      thapsigargin and monensin; this implies the existence of a third pool, besides
      the acidic pool and the Endoplasmic Reticulum (ER), which participates in calcium
      homeostasis. The ER calcium pool can de discharged by the addition of the second
      messenger, IP3, and we present evidence, based on confocal microscopy, that the
      IP3 receptors are located in or close to the nucleus.

PMID- 11969249
TI  - Store-operated Ca2+ entry uncoupled with ryanodine receptor and junctional
      membrane complex in heart muscle cells.
AB  - Store-operated Ca2+ entry (SOCE) is the Ca2+ influx that is activated on
      depletion of intracellular Ca2+ stores. Although SOCE is found in a variety of
      cell types, its activation mechanism and molecular identity remain to be
      clarified. Current experimental results suggest that SOCE channels are activated
      by direct coupling with Ca2+ release channels on depleted stores. Here we report
      SOCE in cardiac myocytes, that was prominently sensitive to Zn2+ but resistant to
      inhibitors for voltage-dependent Ca2+ channels and Na+/Ca2+ exchangers. The SOCE
      activity may be developmentally regulated, because the SOCE was easily detected
      during embryonic and neonatal stages but not in mature myocytes from adult
      hearts. In cardiac myocytes, ryanodine receptor type 2 (RyR-2) is thought to be
      the sole Ca2+ release channel on the intracellular store, and junctophilin type 2
      (JP-2) contributes to formation of the junctional complex between the cell
      surface and store membranes. Using the knockout mice, we also examined possible
      involvement of the Ca2+ release channel and junctional membrane complex in
      cardiac SOCE. Apparently normal SOCE activities were retained in mutant myocytes
      lacking RyR-2 or JP-2, suggesting that neither the Ca2+ release channel nor
      junctional membrane complex is involved in activation of cardiac SOCE.

PMID- 11969250
TI  - Mitochondria respond to Ca2+ already in the submicromolar range: correlation with
      redox state.
AB  - Rapid formation of high-Ca2+ perimitochondrial cytoplasmic microdomains has been
      shown to evoke mitochondrial Ca2+ signal and activate mitochondrial
      dehydrogenases, however, the significance of submicromolar cytoplasmic Ca2+
      concentrations in the control of mitochondrial metabolism has not been
      sufficiently elucidated. Here we studied the mitochondrial response to
      application of Ca2+ at buffered concentrations in permeabilized rat adrenal
      glomerulosa cells, in an insulin-producing cell line (INS-1/EK-3) and in an
      osteosarcoma cell line (143BmA-13). Mitochondrial Ca2+ concentration was measured
      with the fluorescent dye rhod-2 and, using an in situ calibration method, with
      the mitochondrially targeted luminescent protein mt-aequorin. In both endocrine
      cell types, mitochondrial Ca2+ concentration increased in response to elevated
      cytoplasmic Ca2+ concentration (between 60 and 740 nM) and an increase in
      mitochondrial Ca2+ concentration could be revealed already at a cytoplasmic Ca2+
      concentration step from 60-140 nM. Similar responses were observed in the
      osteosarcoma cell line, although a clearcut response was first observed at 280 nM
      extramitochondrial Ca2+ only. As examined in glomerulosa cells, graded increases
      in cytoplasmic Ca2+ concentration were associated with graded increases in the
      reduction of mitochondrial pyridine nucleotides, consistent with Ca2+-dependent
      activation of mitochondrial dehydrogenases. Our data indicate that in addition to
      the recognized role of high-Ca2+ cytoplasmic microdomains, also small Ca2+
      signals may influence mitochondrial metabolism.

PMID- 11969251
TI  - The major yolk protein in sea urchins is a transferrin-like, iron binding
      protein.
AB  - The major yolk protein (MYP) in sea urchins has historically been classified as a
      vitellogenin based on its abundance in the yolk platelets. Curiously, it is found
      in both sexes of sea urchins where it is presumed to play a physiological role in
      gametogenesis, embryogenesis, or both. Here we present the primary structure of
      MYP as predicted from cDNAs of two sea urchins species, Strongylocentrotus
      purpuratus and Lytechinus variegatus. The sequence from these two species share
      identity to one another, but bear no resemblance to other known vitellogenins.
      Instead the sequence shares identity to members of the transferrin superfamily of
      proteins. In vitro iron binding assays, including both (59)Fe overlay assays of
      MYP enriched coelomic fluid and immunoprecipitation of native iron-bound MYP from
      coelomic fluid, support this classification. We suggest that one of MYP's
      transferrin-like properties is to shuttle iron to developing germ cells.

PMID- 11969252
TI  - Ectopic expression of AP-2alpha transcription factor in the lens disrupts fiber
      cell differentiation.
AB  - AP-2alpha is a developmentally important transcription factor which has been
      implicated in the regulation of cell growth, programmed cell death, and
      differentiation. To investigate the specific function of AP-2alpha in
      differentiation of the lens, AP-2alpha was expressed in the differentiating lens
      fiber cells under control of the alphaA-crystallin promoter. Normally, AP-2alpha
      is selectively expressed in lens epithelial cells and expression terminates at
      the lens equator, where epithelial cells terminally differentiate into fiber
      cells. Ectopic expression of the AP-2alpha gene in the fiber cell compartment
      resulted in bilateral cataracts and microphthalmia in mice by 2 weeks of age.
      Histological evaluation of embryonic and adult transgenic lenses revealed a
      significant reduction in lens size and anterior shifting of the transitional
      zone. Two aspects of fiber cell differentiation were also blocked, including the
      migration of newly formed fiber cells and an inhibition in fiber cell
      denucleation. Correlated with these defects were expanded expression of E
      cadherin in the lens transitional zone and reduced expression of the fiber cell
      specific protein MIP (major intrinsic protein). Together, these data demonstrate
      that AP-2alpha acts as a negative regulator of terminal fiber cell
      differentiation through the regulation of genes involved in cell adhesion and
      migration.

PMID- 11969253
TI  - Maternal and zygotic expression of a nanos-class gene in the leech Helobdella
      robusta: primordial germ cells arise from segmental mesoderm.
AB  - The nanos-class gene of the leech Helobdella robusta (Hro-nos) is present as a
      maternal transcript whose levels decay during cleavage; HRO-NOS protein is more
      abundant in the D quadrant cells relative to the A, B, and C quadrants; and HRO
      NOS is more abundant in the ectodermal precursor cell (DNOPQ) than in its sister
      mesodermal precursor (DM) (Pilon and Weisblat, 1997). Here, using in situ
      hybridization, we show that Hro-nos mRNA is broadly distributed throughout the
      zygote, is concentrated in both animal and vegetal teloplasm during stage 1 and
      is at higher levels in DNOPQ than in DM at stage 4b. Hro-nos expression increases
      after stage 7, as judged by in situ hybridization, developmental RT-PCR, and
      western blots; this increase must therefore represent later zygotic expression.
      Of particular interest, during stages 9 and 10, each of 11 mid-body segments (M8
      M18) has a pair of Hro-nos positive "spots" comprising of one or two large cells
      each. These spots later disappear in an anteroposterior progression. We find that
      these Hro-nos-expressing cells are of mesodermal origin, arising in a segmentally
      iterated manner from the M lineage, and correspond to cells previously proposed
      as primordial germ cells (PGCs; Burger, 1891; Weisblat and Shankland, 1985).
      These results support the proposal that nanos-class genes functioned in the
      specification of germline cells in the ancestral bilaterian and possibly in a
      separate process related to embryonic polarity in the ancestral protostome.

PMID- 11969254
TI  - Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell
      population.
AB  - Mammary epithelium can functionally regenerate upon transplantation. This renewal
      capacity has been classically ascribed to the function of a multipotent mammary
      gland stem cell population, which has been hypothesized to be a primary target in
      the etiology of breast cancer. Several complementary approaches were employed in
      this study to identify and enrich mammary epithelial cells that retain stem cell
      characteristics. Using long-term BrdU labeling, a population of label retaining
      cells (LRCs) that lack expression of differentiation markers has been identified.
      LRCs isolated from mammary primary cultures were enriched for stem cell antigen-1
      (Sca-1) and Hoechst dye-effluxing "side population" properties. Sca-1(pos) cells
      in the mammary gland were localized to the luminal epithelia by using Sca
      1(+/GFP) mice, were progesterone receptor-negative, and did not bind peanut
      lectin. Finally, the Sca-1(pos) population is enriched for functional
      stem/progenitor cells, as demonstrated by its increased regenerative potential
      compared with Sca-1(neg) cells when transplanted into the cleared mammary fat
      pads of host mice.

PMID- 11969255
TI  - Distinct enhancers regulate skeletal and cardiac muscle-specific expression
      programs of the cardiac alpha-actin gene in Xenopus embryos.
AB  - During vertebrate embryonic development, cardiac and skeletal muscle originates
      from distinct precursor populations. Despite the profound structural and
      functional differences in the striated muscle tissue they eventually form, such
      progenitors share many features such as components of contractile apparatus. In
      vertebrate embryos, the alpha-cardiac actin gene encodes a major component of the
      myofibril in both skeletal and cardiac muscle. Here, we show that expression of
      Xenopus cardiac alpha-actin in the myotomes and developing heart tube of the
      tadpole requires distinct enhancers within its proximal promoter. Using
      transgenic embryos, we find that mutations in the promoter-proximal CArG box and
      5 bp downstream of it specifically eliminate expression of a GFP transgene within
      the developing heart, while high levels of expression in somitic muscle are
      maintained. This sequence is insufficient on its own to limit expression solely
      to the myocardium, such restriction requiring multiple elements within the
      proximal promoter. Two additional enhancers are active in skeletal muscle of the
      embryo, either one of which has to interact with the proximal CArG box for
      correct expression to be established. Transgenic reporters containing
      multimerised copies of CArG box 1 faithfully detect most sites of SRF expression
      in the developing embryo as do equivalent reporters containing the SRF binding
      site from the c-fos promoter. Significantly, while these motifs possess a
      different A/T core within the CC(A/T)(6)GG consensus and show no similarity in
      flanking sequence, each can interact with a myotome-specific distal enhancer of
      cardiac alpha-actin promoter, to confer appropriate cardiac alpha-actin-specific
      regulation of transgene expression. Together, these results suggest that the role
      of CArG box 1 in the cardiac alpha-actin gene promoter is to act solely as a high
      affinity SRF binding site.

PMID- 11969256
TI  - Germline X chromosomes exhibit contrasting patterns of histone H3 methylation in
      Caenorhabditis elegans.
AB  - In mammals, one of the two somatic X chromosomes in the female is inactivated,
      thereby equalizing X chromosome-derived transcription in the two sexes, a process
      known as dosage compensation. In the germline, however, the situation is quite
      different. Both X chromosomes are transcriptionally active during female
      oogenesis, whereas the X and Y chromosomes are transcriptionally silent during
      male spermatogenesis. Previous studies suggest that Caenorhabditis elegans
      germline X chromosomes might have different transcriptional activity in the two
      sexes in a manner similar to that in mammals. Using antibodies specific to H3
      methylated at either lysine 4 or lysine 9, we show that the pattern of site
      specific H3 methylation is different between X chromosomes and autosomes as well
      as between germline X chromosomes from the two sexes in C. elegans. We show that
      the pachytene germline X chromosomes in both sexes lack Me(K4)H3 when compared
      with autosomes, consistent with their being transcriptionally inactive. This
      transcriptional inactivity of germline X chromosomes is apparently transient in
      hermaphrodites because both X chromosomes stain brightly for Me(K4)H3 after germ
      nuclei exit pachytene. The male single X chromosome, on the other hand, remains
      devoid of Me(K4)H3 staining throughout the germline. Instead, the male germline X
      chromosome exhibits a high level of Me(K9)H3 that is not detected on any other
      chromosomes in either sex, consistent with stable silencing of this chromosome.
      Using mutants defective in the sex determination pathway, we show that X
      chromosomal Me(K9)H3 staining is determined by the sexual phenotype, and not
      karyotype, of the animal. We detect a similar high level of Me(K9)H3 in male
      mouse XY bodies, suggesting an evolutionarily conserved mechanism for silencing
      the X chromosome specifically in the male germline.

PMID- 11969257
TI  - Noggin and chordin have distinct activities in promoting lineage commitment of
      mouse embryonic stem (ES) cells.
AB  - To examine the role of secreted signaling molecules and neurogenic genes in early
      development, we have developed a culture system for the controlled
      differentiation of mouse embryonic stem (ES) cells. In the current investigation,
      two of the earliest identified BMP antagonists/neural-inducing factors, noggin
      and chordin, were expressed in pluripotent mouse ES cells. Neurons were present
      as early as 24 h following transfection of ES cells with a pCS2/noggin expression
      plasmid, with differentiation peaking at 72 h. With neuronal differentiation,
      stem cell marker genes were down-regulated and neural determination genes
      expressed. Coculture experiments and exposure to noggin-conditioned medium
      produced similar neuronal differentiation of control ES cells, while addition of
      BMP-4 to noggin expressants strikingly inhibited neuronal differentiation.
      Transfection of ES cells with a pCS2/chordin expression vector or exposure to
      chordin-conditioned medium produced a more complex pattern of differentiation; ES
      cells formed neurons, mesenchymal cells as well as N-CAM-positive, nestin
      positive neuroepithelial progenitors. These data suggest that, consistent with
      their different expression fields, noggin and chordin may play distinct roles in
      patterning the early mouse embryo.

PMID- 11969259
TI  - Modulation of BMP activity in dorsal-ventral pattern formation by the chordin and
      ogon antagonists.
AB  - We analyzed the interactions between mutations in antagonistic BMP pathway
      signaling components to examine the roles that the antagonists play in regulating
      BMP signaling activity. The dorsalized mutants swirl/bmp2b, snailhouse/bmp7, lost
      a-fin/alk8, and mini fin/tolloid were each analyzed in double mutant combinations
      with the ventralized mutants chordino/chordin and ogon, whose molecular nature is
      not known. Similar to the BMP antagonist chordino, we found that the BMP ligand
      mutants swirl/bmp2b and snailhouse/bmp7 are also epistatic to the putative BMP
      pathway antagonist, ogon, excluding a class of intracellular antagonists as
      candidates for ogon. In ogon;mini fin double mutants, we observed a mutual
      suppression of the ogon and mini fin mutant phenotypes, frequently to a wild type
      phenotype. Thus, the Tolloid/Mini fin metalloprotease that normally cleaves and
      inhibits Chordin activity is dispensable, when Ogon antagonism is reduced. These
      results suggest that Ogon encodes a Tolloid and Chordin-independent antagonistic
      function. By analyzing genes whose expression is very sensitive to BMP signaling
      levels, we found that the absence of Ogon or Chordin antagonism did not increase
      the BMP activity remaining in swirl/bmp2b or hypomorphic snailhouse/bmp7 mutants.
      These results, together with other studies, suggest that additional molecules or
      mechanisms are essential in generating the presumptive gastrula BMP activity
      gradient that patterns the dorsal-ventral axis. Lastly we observed a striking
      increased penetrance of the swirl/bmp2b dominant dorsalized phenotype, when
      Chordin function is also absent. Loss of the BMP antagonist Chordin is expected
      to increase BMP signaling levels in a swirl heterozygote, but instead we observed
      an apparent decrease in BMP signaling levels and a loss of ventral tail tissue.
      As has been proposed for the fly orthologue of chordin, short gastrulation, our
      paradoxical results can be explained by a model whereby Chordin both antagonizes
      and promotes BMP activity.

PMID- 11969258
TI  - Role of Runx genes in chondrocyte differentiation.
AB  - Runx2/Cbfa1 plays a central role in skeletal development as demonstrated by the
      absence of osteoblasts/bone in mice with inactivated Runx2/Cbfa1 alleles. To
      further investigate the role of Runx2 in cartilage differentiation and to assess
      the potential of Runx2 to induce bone formation, we cloned chicken Runx2 and
      overexpressed it in chick embryos using a retroviral system. Infected chick wings
      showed multiple phenotypes consisting of (1) joint fusions, (2) expansion of
      carpal elements, and (3) shortening of skeletal elements. In contrast, bone
      formation was not affected. To investigate the function of Runx2/Cbfa1 during
      cartilage development, we have generated transgenic mice that express a dominant
      negative form of Runx2 in cartilage. The selective inactivation of Runx2 in
      chondrocytes results in a severe shortening of the limbs due to a disturbance in
      chondrocyte differentiation, vascular invasion, osteoclast differentiation, and
      periosteal bone formation. Analysis of the growth plates in transgenic mice and
      in chick limbs shows that Runx2 is a positive regulator of chondrocyte
      differentiation and vascular invasion. The results further indicate that Runx2
      promotes chondrogenesis either by maintaining or by initiating early chondrocyte
      differentiation. Furthermore, Runx2 is essential but not sufficient to induce
      osteoblast differentiation. To analyze the role of runx genes in skeletal
      development, we performed in situ hybridization with Runx2- and Runx3-specific
      probes. Both genes were coexpressed in cartilaginous condensations, indicating a
      cooperative role in the regulation of early chondrocyte differentiation and thus
      explaining the expansion/maintenance of cartilage in the carpus and joints of
      infected chick limbs.

PMID- 11969260
TI  - Zygotic Wnt/beta-catenin signaling preferentially regulates the expression of
      Myf5 gene in the mesoderm of Xenopus.
AB  - Zygotic Wnt signaling has been shown to be involved in dorsoventral mesodermal
      patterning in Xenopus embryos, but how it regulates different myogenic gene
      expression in the lateral mesodermal domains is not clear. Here, we use transient
      exposure of embryos or explants to lithium, which mimics Wnt/beta-catenin
      signaling, as a tool to regulate the activation of this pathway at different
      times and places during early development. We show that activation of Wnt/beta
      catenin signaling at the early gastrula stage rapidly induces ectopic expression
      of XMyf5 in both the dorsal and ventral mesoderm. In situ hybridization analysis
      reveals that the induction of ectopic XMyf5 expression in the dorsal mesoderm
      occurs within 45 min and is not blocked by the protein synthesis inhibitor
      cycloheximide. By contrast, the induction of XMyoD is observed after 2 h of
      lithium treatment and the normal expression pattern of XMyoD is blocked by
      cycloheximide. Analysis by RT-PCR of ectodermal explants isolated soon after
      midblastula transition indicates that lithium also specifically induces XMyf5
      expression, which takes place 30 min following lithium treatment and is not
      blocked by cycloheximide, arguing strongly for an immediate-early response. In
      the early gastrula, inhibition of Wnt/beta-catenin signaling blocks the
      expression of XMyf5 and XMyoD, but not of Xbra. We further show that zygotic
      Wnt/beta-catenin signaling interacts specifically with bFGF and eFGF to promote
      XMyf5 expression in ectodermal cells. These results suggest that Wnt/beta-catenin
      pathway is required for regulating myogenic gene expression in the presumptive
      mesoderm. In particular, it may directly activate the expression of the XMyf5
      gene in the muscle precursor cells.

PMID- 11969261
TI  - Transcription factor AP-2 is an essential and direct regulator of epidermal
      development in Xenopus.
AB  - Expression of the Xenopus homolog of the mammalian transcription factor AP-2alpha
      (XAP-2) is activated throughout the animal hemisphere shortly after the
      midblastula transition, and becomes restricted to prospective epidermis by the
      end of gastrulation, under the control of BMP signal modulation. Elevated
      expression in the future neural crest region begins at this time. Ectopic
      expression of XAP-2 can restore transcription of epidermal genes in neuralized
      ectoderm, both in ectodermal explants and in the intact embryo. Likewise, loss of
      XAP-2 function, accomplished by injection of antisense oligonucleotides or by
      overexpression of antimorphic XAP-2 derivatives, leads to loss of epidermal and
      gain of neural gene expression. These treatments also result in gastrulation
      failure. Thus, AP-2 is a critical regulator of ectodermal determination that is
      required for normal epidermal development and morphogenesis in the frog embryo.

PMID- 11969262
TI  - Programmed cell death is required for palate shelf fusion and is regulated by
      retinoic acid.
AB  - The actual role of programmed cell death (PCD) in embryonic processes and the
      extrinsic signals that define the death fate in developing cells are still poorly
      understood. Here, we show that during secondary palate shelf fusion in the mouse,
      PCD appeared in the medial edge epithelia (MEE) of the anterior region only after
      shelf contact. Contact was necessary for efficient cell death activation in the
      MEE. However, exogenous all-trans-retinoic acid (RA) increased cell death
      independently of contact. Competence to induce cell death by contact or by RA
      exposure was obtained when the MEE were close to touch. Endogenous RA is a
      relevant regulator of the secondary palate PCD since this was reduced by a
      retinol dehydrogenase inhibitor and an RAR specific antagonist. Bmp-7 expression
      was positively regulated by RA. However, BMP-7 was unable to activate cell death
      within the palate tissue and NOGGIN, a natural BMP antagonist, did not block PCD.
      Reduction of PCD at the MEE directly with a caspase inhibitor or by inhibiting
      retinol dehydrogenase resulted in unfused palate shelves, but adhesion was not
      affected. In contrast, exogenous RA also blocked fusion, but in this situation
      the increased cell death within the MEE appeared to affect adhesion, thereby
      causing cleft palate in vivo.

PMID- 11969264
TI  - Ecdysone triggers the expression of Golgi genes in Drosophila imaginal discs via
      broad-complex.
AB  - One of the most significant morphogenic events in the development of Drosophila
      melanogaster is the elongation of imaginal discs during puparium formation. We
      have shown that this macroscopic event is accompanied by the formation of Golgi
      stacks from small Golgi larval clusters of vesicles and tubules that are present
      prior to the onset of disc elongation. We have shown that the fly steroid hormone
      20-hydroxyecdysone triggers both the elongation itself and the formation of Golgi
      stacks (V. Kondylis, S. E. Goulding, J. C. Dunne, and C. Rabouille, 2001, Mol.
      Biol. Cell, 12, 2308). Using mRNA in situ hybridisation, we show here that
      ecdysone triggers the upregulation of a subset of genes encoding Golgi-related
      proteins (such as dnsf1, dsec23, dsed5, and drab1) and downregulates the
      expression of others (such as dergic53, dbeta'COP, and drab6). We show that the
      transcription factor Broad-complex, itself an "early" ecdysone target, mediates
      this regulation. And we show that the ecdysone-independent upregulation of dnsf1
      and dsnap prior to the ecdysone peak leads to a precocious formation of large
      Golgi stacks. The ecdysone-triggered biogenesis of Golgi stacks at the onset of
      imaginal disc elongation offers the exciting possibility of advancing our
      understanding of the relationship between gene expression and organelle
      biogenesis.

PMID- 11969263
TI  - Deregulated expression of the homeobox gene Cux-1 in transgenic mice results in
      downregulation of p27(kip1) expression during nephrogenesis, glomerular
      abnormalities, and multiorgan hyperplasia.
AB  - Cux-1 is a murine homeobox gene that is highly expressed in the developing kidney
      with expression restricted to the nephrogenic zone. Cux-1 is highly expressed in
      cyst epithelium of polycystic kidneys from C57BL/6J-cpk/cpk mice, but not in
      kidneys isolated from age-matched phenotypically normal littermates. To further
      elucidate the role of Cux-1 in renal development, we generated transgenic mice
      expressing Cux-1 under the control of the CMV immediate early gene promoter. Mice
      constitutively expressing Cux-1 developed multiorgan hyperplasia and
      organomegaly, but not an overall increase in body size. Transgenic kidneys were
      enlarged 50% by 6 weeks of age, with the increased growth primarily restricted to
      the cortex. Proliferating cells were found in proximal and distal tubule
      epithelium throughout the cortex, and the squamous epithelium that normally lines
      Bowman's capsule was replaced with proximal tubule epithelium. However, the total
      number of nephrons was not increased. In the developing kidneys of transgenic
      mice, Cux-1 was ectopically expressed in more highly differentiated tubules and
      glomeruli, and this was associated with reduced expression of the cyclin kinase
      inhibitor, p27. Transient transfection experiments revealed that Cux-1 is an
      inhibitor of p27 promoter activity. These results suggest that Cux-1 regulates
      cell proliferation during early nephrogenesis by inhibiting expression of p27.

PMID- 11969265
TI  - Analysis of spatial and temporal gene expression patterns in blastula and
      gastrula stage chick embryos.
AB  - Studies on the genetic basis of rostral-caudal specification, neural induction,
      and head development require knowledge of the relevant gene expression patterns.
      Gaps in our understanding of gene expression have led us to examine the detailed
      spatiotemporal expression patterns of 19 genes implicated in early development,
      to learn more about their potential role in specifying and patterning early
      developmental processes leading to head formation. Here, we report the expression
      patterns of these markers in blastula- and gastrula-stage chick embryos, using
      whole-mount in situ hybridisation. Nodal, Fgf8, Bmp7, Chordin, Lim1, Hnf3beta,
      Otx2, Goosecoid, Cerberus, Hex, Dickkopf1, and Crescent are all already expressed
      by the time the egg is laid. When the primitive streak has reached its full
      length, a later group of genes, including Ganf, Six3, Bmp2, Bmp4, Noggin,
      Follistatin, and Qin (BF1), begins to be expressed. We reassess current models of
      early rostral patterning based on the analysis of these dynamic spatiotemporal
      expression patterns.

PMID- 11969266
TI  - A potential role for AMP-activated protein kinase in meiotic induction in mouse
      oocytes.
AB  - Cyclic adenosine monophosphate (cAMP) has been implicated as an important
      regulator of meiotic maturation in mammalian oocytes. A decrease in cAMP, brought
      about by the action of cAMP phosphodiesterase (PDE), is thought to initiate
      germinal vesicle breakdown (GVB) by the inactivation of cAMP-dependent protein
      kinase. However, the product of PDE activity, 5'-AMP, is a potent activator of an
      important regulatory enzyme, AMP-activated protein kinase (AMPK). The aim of this
      study was to evaluate a possible role for AMPK in meiotic induction, using
      oocytes obtained from eCG-primed, immature mice. Alpha-1 and -2 isoforms of the
      catalytic subunit of AMPK were detected in both oocytes and cumulus cells. When 5
      aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICA riboside), an
      activator of AMPK, was tested on denuded oocytes (DO) and cumulus cell-enclosed
      oocytes (CEO) maintained in meiotic arrest by dbcAMP or hypoxanthine, GVB was
      dose-dependently induced. Meiotic induction by AICA riboside in dbcAMP
      supplemented medium was initiated within 3 h in DO and 4 h in CEO and was
      accompanied by increased AMPK activity in the oocyte. AICA riboside also
      triggered GVB when meiotic arrest was maintained with hypoxanthine, 8-AHA-cAMP,
      guanosine, or milrinone, but was ineffective in olomoucine- or roscovitine
      arrested oocytes, indicating that it acts upstream of maturation-promoting
      factor. Adenosine monophosphate dose-dependently stimulated GVB in DO when
      meiotic arrest was maintained with dbcAMP or hypoxanthine. This effect was not
      mimicked by other monophosphate or adenosine nucleotides and was not affected by
      inhibitors of ectophosphatases. Combined treatment with adenosine and
      deoxycoformycin, an adenosine deaminase inhibitor, stimulated GVB in dbcAMP
      arrested CEO, suggesting AMPK activation due to AMP accumulation. It is concluded
      that phosphodiesterase-generated AMP may serve as a transducer of the meiotic
      induction process through activation of AMPK.

PMID- 11969267
TI  - Essential and redundant functions of the MyoD distal regulatory region revealed
      by targeted mutagenesis.
AB  - Transgenic analyses have defined two MyoD enhancers in mammals, the core enhancer
      and distal regulatory region (DRR); these enhancers exhibit complementary
      activities and together are sufficient to recapitulate MyoD expression in
      developing and mature skeletal muscle. DRR activity is restricted to
      differentiated muscle and persists postnatally, suggesting an important role in
      maintaining MyoD expression in myocytes and muscle fibers. Here, we use targeted
      mutagenesis in the mouse to define essential functions of the DRR in its normal
      chromosomal context. Surprisingly, deletion of the DRR resulted in reduced MyoD
      expression in all myogenic lineages at E10.5, at least 1 day prior to detection
      of DRR activity in limb buds and branchial arches of transgenic mice. At later
      embryonic and fetal stages, however, no defect in MyoD expression was observed,
      indicating that the DRR is dispensable for regulating MyoD during muscle
      differentiation. Expression analyses in wild-type and Myf-5 mutant embryos also
      indicate that the DRR is not an obligate target for Myf-5- and Pax-3-dependent
      regulation. In contrast to embryonic and fetal stages, deletion of the DRR
      resulted in a pronounced reduction in MyoD mRNA levels in adults, showing a
      functional requirement for DRR activity in mature muscle. These data reveal
      essential and redundant functions of the DRR and underscore the importance of
      loss-of-function enhancer analyses for understanding cis transcriptional
      circuitry.

PMID- 11969268
TI  - Posttranscriptional regulation of p18 and p27 Cdk inhibitor proteins and the
      timing of oligodendrocyte differentiation.
AB  - A cell-intrinsic timer helps control when rodent oligodendrocyte precursor cells
      (OPCs) exit the cell cycle and terminally differentiate when cultured in platelet
      derived growth factor (PDGF) and thyroid hormone (TH). There is evidence that the
      cyclin-dependent kinase inhibitor (CKI) p27/Kip1 (p27) is a component of this TH
      regulated timer, as it increases as OPCs proliferate and is required for the
      timer to operate accurately. Here, we provide evidence that another CKI, p18/INK
      (p18), may also be a component of the timer: it increases as OPCs proliferate,
      and its overexpression in OPCs accelerates the timer, causing the cells to
      differentiate prematurely. We also show that the overexpression of p27
      accelerates the timer and that the increases in both p27 and p18 that occur in
      proliferating OPCs are controlled posttranscriptionally. By contrast, we show
      that the overexpression of either p18 or p27 in OPCs proliferating in PDGF and
      the absence of TH greatly slows the cell cycle but fails to accelerate the
      spontaneous differentiation that normally occurs independently of TH.

PMID- 11969269
TI  - Coronary risk - time for a more sophisticated approach?

PMID- 11969270
TI  - Enoxaparin in ST elevation MI - a bright future.

PMID- 11969271
TI  - Direct stenting: safe with advantages for the patient and for the doctor (less
      fluoroscopy and procedural time).

PMID- 11969272
TI  - The stent is here to stay: a note on stenting, ultrasound imaging, and the
      prevention of restenosis.

PMID- 11969273
TI  - Substantial variations in clinical outcome following hospitalization for heart
      failure.

PMID- 11969274
TI  - Does pre-operative education of patients improve outcomes? The impact of pre
      operative education on recovery following coronary artery bypass surgery: a
      randomized controlled clinical trial.

PMID- 11969275
TI  - Assessment of myocardial viability by cardiovascular magnetic resonance imaging.

PMID- 11969276
TI  - Coronary heart disease risk factors ranked by importance for the individual and
      community. A 21 year follow-up of 12 000 men and women from The Copenhagen City
      Heart Study.
AB  - AIMS: The importance of coronary heart disease risk factors may differ between
      individuals and community and by sex and age. METHODS AND RESULTS The Copenhagen
      City Heart Study followed for 21 years a random sample of 5599 men and 6478 women
      aged 30 to 79 years at baseline. The importance of risk factors in individuals
      and the community were evaluated as relative- and population-attributable risks.
      We traced 2180 coronary events. In Cox regression analysis with ten risk factors
      entered simultaneously, relative risks for coronary heart disease in men ranged
      from 1.69 to 1.20 with the highest risks for diabetes, hypertension, smoking, and
      physical inactivity. In women, relative risks ranged from 2.74 to 1.19 with the
      highest risks for diabetes, smoking, hypertension, and physical inactivity.
      Population-attributable risks in men ranged from 22% to 3% with the highest risks
      for smoking, hypertension, and no daily alcohol intake. In women, attributable
      risks ranged from 37% to 3% with the highest risks for smoking, hypertension, and
      hypercholesterolaemia. Several of these rankings differed by age. CONCLUSIONS:
      The importance of coronary heart disease risk factors may differ for individuals,
      the community, and by sex and age. Consequently, prevention strategies should be
      tailored accordingly.

PMID- 11969277
TI  - Randomized comparison of enoxaparin with unfractionated heparin following
      fibrinolytic therapy for acute myocardial infarction.
AB  - AIMS: To compare the efficacy and safety of low molecular weight heparin with
      unfractionated heparin following fibrinolytic therapy for acute myocardial
      infarction. METHODS AND RESULTS: Three-hundred patients receiving fibrinolytic
      therapy following acute myocardial infarction were randomly assigned to low
      molecular weight heparin as enoxaparin (40 mg intravenous bolus, then 40 mg
      subcutaneously every 8 h, n=149) or unfractionated heparin (5000 U intravenous
      bolus, then 30 000 U. 24 h(-1), adjusted to an activated partial thromboplastin
      time 2-2.5x normal, n=151) for 4 days in conjunction with routine therapy.
      Clinical and therapeutic variables were analysed, in addition to use of
      enoxaparin or unfractionated heparin, to determine independent predictors of the
      90-day composite triple end-point (death, non-fatal reinfarction, or readmission
      with unstable angina). The triple end-point occurred more frequently in patients
      receiving unfractionated heparin rather than enoxaparin (36% vs. 26%; P=0.04).
      Logistic regression modelling of baseline and clinical variables identified the
      only independent risk factors for recurrent events as left ventricular failure,
      hypertension, and use of unfractionated heparin rather than enoxaparin. There was
      no difference in major haemorrhage between those receiving enoxaparin (3%) and
      unfractionated heparin (4%). CONCLUSION: Use of enoxaparin compared with
      unfractionated heparin in patients receiving fibrinolytic therapy for acute
      myocardial infarction was associated with fewer recurrent cardiac events at 90
      days. This benefit was independent of other important clinical and therapeutic
      factors.

PMID- 11969278
TI  - Direct coronary stenting versus stenting with balloon pre-dilation: immediate and
      follow-up results of a multicentre, prospective, randomized study. The DISCO
      trial. DIrect Stenting of COronary Arteries.
AB  - AIMS: To assess the safety of direct coronary stenting, its influence on costs,
      duration of the procedure, radiation exposure, clinical outcome and angiographic
      restenosis. METHODS AND RESULTS: We randomized 416 patients (446 lesions) to
      direct stent implant or stent implant following balloon pre-dilation. Patients
      >75 years old, heavily calcified lesions, bifurcations, total occlusions, left
      main lesions and very tortuous vessels were excluded. Direct stenting was
      successful in 217/224 lesions (96.8%). No single loss or embolization of the
      stent occurred. All stents in the group with pre-dilation were effectively
      deployed. The immediate post-procedure angiographic results were similar with
      both techniques. Fluoroscopy and procedural time were significantly lower in
      direct stenting (6.4+/-0.3 and 21+/-0.9 min) than in pre-dilated stenting (9.1+/
      0.4 and 27.5+/-1.1 min) (P>0.001). Major adverse cardiac events during
      hospitalization were one in direct and four in pre-dilated stenting (P=0.05) but
      there were no significant differences at follow-ups at 1, 6 and 12 months between
      the two groups. Angiographic reevaluation at 6 months was performed in 94% of the
      cases. Restenosis rate was 16.5% in direct stenting and 14.3% in pre-dilated
      stenting (P=ns). CONCLUSIONS: Direct stenting is as safe as pre-dilated stenting
      in selected coronary lesions. Acute angiographic results are similar but
      procedural costs, duration of the procedure and radiation exposure are lower in
      direct stenting. Overall success rate, mid-term clinical outcome and restenosis
      are similar with both techniques.

PMID- 11969279
TI  - Initial observation regarding changes in vessel dimensions after balloon
      angioplasty and stenting followed by catheter-based beta-radiation. Is stenting
      necessary in the setting of catheter-based radiotherapy?
AB  - AIMS: We sought to compare the effect of intracoronary beta-radiation on the
      vessel dimensions in de novo lesions using three-dimensional intravascular
      ultrasound quantification after balloon angioplasty and stenting. METHODS AND
      RESULTS: Forty patients (44 vessels; 28 balloon angioplasty and 16 stenting)
      treated with catheter-based beta-radiation and 18 non-irradiated control patients
      (18 vessels; 10 balloon angioplasty and 8 stenting) were investigated by means of
      three-dimensional volumetric intravascular ultrasound analysis post-procedure and
      at 6-8 months follow-up. Total vessel (EEM) volume enlarged after both balloon
      angioplasty and stenting (+37 mm(3) vs +42 mm(3), P=ns), but vessel wall volume
      (plaque plus media) also increased similarly (+33 mm(3) vs +49 mm(3), P=ns) in
      the irradiated patients. Lumen volume remained unchanged in both groups (+3 mm(3)
      vs -7 mm(3), P=ns). In the stent-covered segments, neointima at follow-up was
      significantly smaller in the irradiated group than the control group (8 mm(3) vs
      27 mm(3), P=0.001, respectively), but the total amount of tissue growth was
      similar in both groups (33 mm(3) vs 29 mm(3), P=ns). CONCLUSIONS: Intracoronary
      beta-radiation induces vessel enlargement after balloon angioplasty and/or
      stenting, accommodating tissue growth. Additional stenting may not play an
      important role in the prevention of constrictive remodelling in the setting of
      catheter-based intracoronary beta-radiotherapy.

PMID- 11969280
TI  - Substantial between-hospital variation in outcome following first emergency
      admission for heart failure.
AB  - BACKGROUND: Following hospitalization with a range of cardiovascular disorders,
      substantial variation has been noted in clinical outcome, both between and within
      countries. OBJECTIVES: To examine the variation, between hospitals, in the
      clinical outcomes of death and readmission following hospitalization with heart
      failure in Scotland. Setting All 29 acute hospitals in Scotland with more than
      200 beds. PATIENTS: All 31 452 patients discharged from these hospitals between
      January 1990 and December 1995 with a first-ever, primary, diagnosis at
      discharge/death of heart failure. ANALYSIS: An analysis of the Scottish database
      of discharge summaries linking index admissions with subsequent admissions and
      deaths. Death rates and readmission rates were adjusted for baseline age, co
      morbidity and socio-economic status and were calculated at different time periods
      (inpatient, 30 days, 1 year). Rates were calculated separately for large teaching
      hospitals (n=6, category A), large general hospitals with specialist units (n=8,
      category B) and medium sized general hospitals with limited specialist units
      (n=15 category C). RESULTS: A total of 31 452 patients were discharged between
      1990-1995 - 10 219 (33%), 9735 (31%) and 11 498 (37%) to category A, B and C
      hospitals, respectively. The national, average, inpatient case fatality rate was
      15.3%, ranging, in individual hospitals, from the lowest rate of 8.5% to the
      highest rate of 23.4%. The average 1 year case fatality rate was 42.4%, ranging
      between 35.3% and 50.8%. A similar two- to threefold variation was found in
      hospital readmission rates - thus the average 30 day readmission rate was 5.3%
      (lowest 3.3%, highest 7.3%). This variation, in both case-fatality and
      readmission rates, was apparent within all three groups of hospitals and
      persisted after adjustment for the baseline factors outlined above. CONCLUSIONS:
      A patient admitted to one Scottish hospital with heart failure may be two to
      three times more likely to die or be readmitted, both in the short and longer
      term, compared to a patient admitted to another hospital. Although we may not
      have accounted for some sources of variation, it is both surprising and
      disturbing that large, statistically significant, differences in adjusted death
      and readmission rates can apparently exist for such an important condition in a
      relatively small country with generally homogenous health care provision.
      Further, detailed investigation of this apparent variation is required.

PMID- 11969281
TI  - Prevalent influence of systolic over pulse pressure on left ventricular mass in
      essential hypertension.
AB  - BACKGROUND: Elevated pulse pressure, an index of increased large artery
      stiffness, has been associated with increased left ventricular mass. It is
      unknown whether this relation is independent or mediated by other blood pressure
      components. METHODS AND RESULTS: We examined data in 2545 untreated hypertensive
      subjects (45% women) who underwent echocardiography and 24-h ambulatory blood
      pressure monitoring. Left ventricular mass increased with all blood pressure
      components and all associations were closer with ambulatory than with office
      blood pressure. In a multiple regression analysis, after adjustment for the
      significant association with age, gender, body weight and duration of
      hypertension, the proportion of variability of left ventricular mass explained by
      systolic blood pressure was greater than that explained by other blood pressure
      components. When different blood pressure components were forced into the same
      model, the same degree of left ventricular mass variability was accounted for by
      models including 24-h systolic blood pressure alone, or 24-h mean blood pressure
      plus 24-h pulse pressure, or 24-h diastolic blood pressure plus 24-h pulse
      pressure. When 24-h systolic blood pressure and 24-h pulse pressure were forced
      into the same model, 24-h pulse pressure lost statistical significance.
      CONCLUSIONS: The association between pulse pressure and left ventricular mass is
      explained by systolic blood pressure, which is the main pressure determinant of
      left ventricular mass in essential hypertension.

PMID- 11969282
TI  - The impact of pre-operative education on recovery following coronary artery
      bypass surgery. A randomized controlled clinical trial.
AB  - AIMS: Research has demonstrated the beneficial impact that pre-operative
      education exerts on the postoperative recovery of patients having surgery but
      little work has focused specifically on cardiac surgery. Therefore a randomized
      controlled trial was designed to elucidate the consequences of pre-operative
      education, given before admission, on postoperative pain, anxiety, depression and
      wellbeing in the 6 months following a first episode of coronary artery surgery.
      METHOD AND RESULTS: Three hundred and fifty-six people were randomized into the
      study, with 188 in the experimental and 168 in the control arms. Patients in the
      experimental group received the intervention, a day of education by members of
      the multidisciplinary team, prior to admission for surgery. Experimental and
      control subjects had the usual care, which involved education on admission and
      throughout their stay in hospital. Measurement was conducted on entry to the
      study, before randomization, and at 3 days, 6 weeks, 3 months and 6 months
      following operation. A variety of tools were used: the SF-36 Health Status
      questionnaire, the Hospital Anxiety and Depression scale, the General Well-Being
      questionnaire and a pain measurement tool. Analysis was done using the intention
      totreat principle and non-parametric statistics. There were no significant
      differences between groups in the primary outcomes namely anxiety (P=0.09) and
      pain (P=0.48), or in depression (P=0.62) and wellbeing ('worn out' P=0.11; 'tense
      and uptight' P=0.29) 6 months after operation. This was also the case 3 days
      after coronary artery surgery. There was a significant difference in length of
      hospital stay (P=0.01) with the experimental group having the longer stay. These
      findings contrast with much of the existing evidence. CONCLUSION: The findings
      demonstrate that there is no benefit to be gained from this form of pre-operative
      education and that there is an associated increase in length of hospital stay.
      Future research could examine an ongoing programme of education and support, and
      might use alternative methods such as CD-ROM or the Internet.

PMID- 11969283
TI  - Brugada syndrome.

PMID- 11969284
TI  - Brugada syndrome: historical perspectives and observations.

PMID- 11969286
TI  - Coupling cAMP signaling to transcription in the liver: pivotal role of CREB and
      CREM.
AB  - Transcriptional factors binding to cAMP-responsive elements (CREs) in the
      promoters of various genes belong to the basic domain-leucine zipper superfamily
      and are composed of three genes in mammals, CREB, CREM, and ATF-1. A large number
      of CREB, CREM, and ATF-1 proteins are generated by posttranscriptional events,
      mostly alternative splicing, and regulate gene expression by acting as activators
      or repressors. Activation is classically brought about by signaling-dependent
      phosphorylation of a key acceptor site (Ser133 in CREB) by a number of possible
      kinases, including PKA, CamKIV, and Rsk-2. Phosphorylation is the prerequisite
      for the interaction of CBP (CREB-binding protein), a co-activator that has also
      histone acetyltransferase activity. Repression may involve dynamic
      dephosphorylation of the activators and thus decreased association with CBP.
      Another pathway of transcriptional repression on CRE sites implicates the
      inducible repressor ICER (inducible cAMP early repressor), a product of the CREM
      gene. Being an inducible repressor, ICER is involved in autoregulatory feedback
      loops of transcription that govern the down-regulation of early response genes,
      such as the proto-oncogene c-fos. The liver represents a remarkable physiological
      setting where cAMP-responsive signaling plays a major role. Indeed, a finely
      tuned program of gene expression is triggered by partial hepatectomy, so that
      through specific checkpoints a coordinated regeneration of the tissue is
      obtained. Temporal kinetics of transcriptional activation after hepatectomy
      reveals a pattern of early induction for several genes, some of them controlled
      by the CREB/CREM transcription factors. An important role of CREM in liver
      physiology was suggested by the robust induction of ICER after partial
      hepatectomy. The delay in tissue regeneration in CREM-deficient mice confirmed
      the important function of this factor in regulating hepatocyte proliferation. As
      gene induction is accompanied by critical changes in chromatin organization, the
      deciphering of the specific modification codes that histones display during liver
      regeneration and physiology will provide exciting new insights into the dynamics
      of chromatin architecture.

PMID- 11969287
TI  - MAGI-1: a widely expressed, alternatively spliced tight junction protein.
AB  - Tight junctions are apically localized structures that regulate the passage of
      small molecules and proteins through intercellular regions of epithelial or
      endothelial cells. These structures are complex multimolecular assemblages that
      contain both transmembrane and membrane-associated proteins. MAGUKs (Membrane
      Associated Guanylate Kinases) are a family of scaffolding proteins that contain
      multiple protein interaction domains, including PDZ, SH3, WW, and guanylate
      kinase motifs, and have been grouped into five discrete subfamilies based on
      homology. Little is known regarding the most recently described subfamily of
      MAGUKs, termed MAGIs (MAGUKS with Inverted domain structure). Here we show that
      two of the three known MAGI isoforms, MAGI-1 and MAGI-3, are present in the tight
      junctions of cultured epithelial cells. A broader examination of MAGI-1
      expression in vivo shows that it is present in the tight junctions of all
      epithelial cell types examined. Human MAGI-1 transcripts are alternatively
      spliced at three sites, and two forms are expressed only in nonepithelial
      tissues, predominantly in brain. The major form that is expressed in cultured
      colon carcinoma epithelial cells, as well as several epithelial-rich tissues,
      contains an extended carboxy terminus encoding potential nuclear targeting
      signals. MAGI-1, ZO-1, and ZO-2 all colocalize in nonpolarized epithelial cells,
      suggesting that they form a preassembled complex that is incorporated into the
      tight junction upon polarization. Finally, all of the alternatively spliced forms
      of MAGI-1 show tight junction localization, and this localization occurs in the
      absence of the guanylate kinase and WW domains as well as the extended carboxy
      terminus.

PMID- 11969288
TI  - Dendrite-like process formation and cytoskeletal remodeling regulated by delta
      catenin expression.
AB  - Actin- and microtubule-mediated changes in cell shape are essential for many
      cellular activities. However, the molecular mechanisms underlying the interplay
      between the two are complex and remain obscure. Here we show that the expression
      of delta-catenin (or NPRAP/Neurojungin), a member of p120(ctn) subfamily of
      armadillo proteins can induce the branching of dendrite-like processes in 3T3
      cells and enhance dendritic morphogenesis in primary hippocampal neurons. This
      induction of branching phenotype involves initially the disruption of filamentous
      actin, and requires the growth of microtubules. The carboxyl-terminal truncation
      mutant of delta-catenin can cluster and redistribute the full-length protein, and
      dominantly inhibit its branching effect. delta-Catenin forms protein complexes
      and can bind directly to actin in vitro. The carboxyl-terminal truncation of
      delta-catenin does not interfere with its actin-binding capability; therefore the
      actin interaction alone is not sufficient for the induction of dendrite-like
      processes. When delta-catenin-transformed cells establish elaborate dendrite-like
      branches, the main cellular processes become stabilized and resist the disruption
      of both actin filaments and microtubules, as determined by fluorescent light
      microscopy and time-lapse recording analyses. We suggest that delta-catenin can
      effect a biphasic cytoskeletal remodeling event which differentially regulates
      actin and microtubules and promotes cellular morphogenesis.

PMID- 11969289
TI  - Expression and distribution of laminin alpha1 and alpha2 chains in embryonic and
      adult mouse tissues: an immunochemical approach.
AB  - Protein levels, mRNA expression, and localization of laminin alpha1 and alpha2
      chains in development and in adult mice were examined. Recombinant fragments were
      used to obtain high-titer-specific polyclonal antibodies for establishing
      quantitative radioimmuno-inhibition assays. This often demonstrated an abundance
      of alpha2 chain, but also distinct amounts of alpha1 chain for adult tissues. The
      highest amounts of alpha1 were found in placenta, kidney, testis, and liver and
      exceeded those of alpha2. All other tissue extracts showed a higher content of
      alpha2, which was particularly high in heart and muscle when compared to alpha1.
      Content of gamma1 chain, shared by most laminins, was also analyzed. This
      demonstrated gamma1 chain levels being equal to or moderately exceeding the sum
      of alpha1 and alpha2 chains, indicating that these isoforms represent the major
      known laminin isoforms in most adult mouse tissues so far examined. Moreover, we
      found good correlation between radioimmuno-inhibition data and mRNA levels of
      adult tissues as measured by quantitative real-time reverse transcriptase-PCR.
      Embryonic tissues were also analyzed by radioimmuno-inhibition assays. This
      demonstrated for day 11 embryos comparable amounts of alpha1 and gamma1 and a
      more than 25-fold lower content of alpha2. This content increased to about 10% of
      alpha1 in day 13 embryos. The day 18 embryo showed in heart, kidney, and liver,
      but not yet in brain and lung, alpha1/alpha2 chain ratios comparable to those in
      adult tissues. Immunostaining demonstrated alpha1 in Reichert's membrane (day
      7.5), while alpha2 could not be detected before day 11.5. These data were
      compared with immunohistochemical localization results on several more embryonic
      and adult tissue sections. Our results regarding localization are consistent with
      those of earlier work with some notable exceptions. This was in part due to
      epitope masking for monoclonal antibodies commonly used in previous studies in
      esophagus, intestine, stomach, liver, kidney, and spleen.

PMID- 11969290
TI  - Exogenous expression of heat shock protein 90kDa retards the cell cycle and
      impairs the heat shock response.
AB  - The 90-kDa heat shock protein, HSP90, is an abundant molecular chaperone which
      functions in cellular homeostasis in prokaryotes and eukaryotes. It is well known
      that HSP90 plays a critical and indispensable role in regulating cell growth
      through modulations of various signal transduction pathways, but its roles in
      cell cycle control are not so well known. We transferred human HSP90 (wild-type
      or mutated types) expression vectors into NIH-3T3 cells in order to study certain
      functions of HSP90 in the cell cycle and cell growth under physiological
      conditions. We found that the exogenous expression of HSP90 (wild-type) induced a
      decrease in cell growth via retardation of the G1/S transition. The inhibition of
      cell growth was caused by reduced expressions of cyclin D3 and cyclin A mRNA and
      protein. On the other hand, no stable transfectants with the three types of
      mutated HSP90 were obtained. Unexpectedly, exogenous HSP90 expression impaired
      the heat shock response by inhibiting both heat shock transcription factor
      1(HSF1) activation and transportation of HSF1 into the nucleus. The HSF1 function
      was disrupted by the direct association between HSF1 and exogenous HSP90, which
      was present as a monomer. These results reveal important roles of HSP90 in cell
      cycle control and in the stress response of nontransformed cells.

PMID- 11969291
TI  - Cross-talk between mesenchyme and epithelium increases H19 gene expression during
      scattering and morphogenesis of epithelial cells.
AB  - The H19 gene is an imprinted gene expressed from the maternal allele. It is known
      to function as an RNA molecule. We previously reported that in breast
      adenocarcinoma, H19 is often overexpressed in stromal cells and preferentially
      located at the epithelium/stroma boundary, suggesting that epithelial/mesenchymal
      interactions can control H19 RNA expression. In some cases of breast
      adenocarcinoma with poor prognosis, H19 is overexpressed in epithelial cells.
      Therefore we examined whether mesenchymal factors can induce H19 expression in
      epithelial cells. Using quantitative RT-PCR and in situ hybridization, we found
      that when mammary epithelial cells were cultured in collagen gels, H19 expression
      was strongly up-regulated compared to when cells were cultured on plastic.
      Collagen gels allow three-dimensional growth of epithelial cells and
      morphogenetic responses to soluble factors. A conditioned medium from MRC-5
      fibroblasts caused branching morphogenesis of HBL-100 cells and invasive growth
      of MDA-MB-231 cells, whereas MCF-7 cells were unresponsive. Induction of H19
      expression correlated with morphological changes in HBL-100 and in MDA-MB-231
      cells, whereas H19 expression was not induced in MCF-7 cells. Using a blocking
      antibody, HGF/SF was identified as the fibroblast-derived growth factor capable
      of inducing H19 expression and cell morphogenesis. We further demonstrated that
      H19 promoter activity was stimulated by various growth factors using transient
      transfection in MDCK epithelial cells. HGF/SF was more efficient than EGF or FGF
      2 in transactivating the H19 promoter, whereas IGF-2, TGFbeta-1, and TNF-alpha
      were ineffective. This activation by HGF/SF was prevented by pharmacological
      inhibition of MAP kinase or of phospholipase C. We conclude that H19 is a target
      gene for HGF/SF, a known regulator of epithelial/mesenchymal interactions, and
      suggest that the up-regulation of H19 may be implicated in morphogenesis and/or
      migration of epithelial cells.

PMID- 11969292
TI  - Macrophages influence a competition of contact guidance and chemotaxis for
      fibroblast alignment in a fibrin gel coculture assay.
AB  - Rat dermal fibroblasts were dispersed initially in the outer shell of a fibrin
      gel sphere, while the inner core either was devoid of cells or contained
      peritoneal exudate cells (primarily macrophages), thereby mimicking the
      inflammatory phase of wound healing. The fibroblasts compacted floating fibrin
      microspheres over time. In the absence of macrophages, the initial distribution
      of fibroblasts (only in the shell) induced circumferential alignment of fibrin
      fibrils via compaction of the shell relative to the core. The aligned fibrils
      created a contact guidance field, which was manifested by strong circumferential
      alignment of the fibroblasts. However, in the presence of macrophages, the
      fibroblasts exhibited more radial alignment despite the simultaneous contact
      guidance field in the circumferential direction associated with compaction. This
      was attributed to a chemotactic gradient emanating from the core due to a
      putative factor(s) released by the macrophages. The presence of a radial
      chemotactic stimulus was supported by the finding of even greater radial
      alignment when fibrin microspheres were embedded in an agarose-fibrin gel that
      abolished compaction and consequently the contact guidance field. Our assay
      permits the simulation of tissue morphogenetic processes that involve cell
      guidance phenomena and tractional restructuring of the extracellular matrix.

PMID- 11969293
TI  - HIV-1 Nef induces dendritic cell differentiation: a possible mechanism of
      uninfected CD4(+) T cell activation.
AB  - Human immunodeficiency virus (HIV)-1 Nef protein is an essential modulator of
      AIDS pathogenesis and we have previously demonstrated that rNef enters uninfected
      human monocytes and induces T cells bystander activation, up-regulating IL-15
      production. Since dendritic cells (DCs) play a central role in HIV-1 primary
      infection we investigated whether rNef affects DCs phenotypic and functional
      maturation in order to define its role in the immunopathogenesis of AIDS. We
      found that rNef up-regulates the expression on immature DCs of surface molecules
      known to be critical for their APC function. These molecules include CD1a, HLA
      DR, CD40, CD83, CXCR4, and to a lower extent CD80 and CD86. On the other hand,
      rNef down-regulates surface expression of HLA-ABC and mannose receptor. The
      functional consequence of rNef treatment of immature DCs is a decrease in their
      endocytic and phagocytic activities and an increase in cytokine (IL-1beta, IL-12,
      IL-15, TNF-alpha) and chemokine (MIP-1alpha, MIP-1beta, IL-8) production as well
      as in their stimulatory capacity. These results indicate that rNef induces a
      coordinate series of phenotypic and functional changes promoting DC
      differentiation and making them more competent APCs. Indeed, Nef induces CD4(+) T
      cell bystander activation by a novel mechanism involving DCs, thus promoting
      virus dissemination.

PMID- 11969294
TI  - A discrete cell cycle checkpoint in late G(1) that is cytoskeleton-dependent and
      MAP kinase (Erk)-independent.
AB  - Cell spreading on extracellular matrix and associated changes in the actin
      cytoskeleton (CSK) are necessary for progression through G(1) and entry into S
      phase of the cell cycle. Pharmacological disruption of CSK integrity inhibits
      early mitogenic signaling to the extracellular signal-regulated kinase (Erk)
      subfamily of the mitogen-activated protein kinases (MAPKs) and arrests the cell
      cycle in G(1). Here we show that this block of G(1) progression is not simply a
      consequence of inhibition of the MAPK/Erk pathway but instead it reveals the
      existence of a discrete CSK-sensitive checkpoint. Use of PD98059 to inhibit
      MAPK/Erk and cytochalasin D (Cyto D) to disrupt the actin CSK at progressive time
      points in G(1) revealed that the requirement for MAPK/Erk activation lasts only
      to mid-G(1), while the actin CSK must remain intact up to late G(1) restriction
      point, R, in order for capillary endothelial cells to enter S phase. Additional
      analysis using Cyto D pulses defined a narrow time window of 3 h just prior to R
      in which CSK integrity was shown to be critical for the G(1)/S transition. Cyto D
      treatment led to down-regulation of cyclin D1 protein and accumulation of the cdk
      inhibitor, p27(Kip1), independent of cell cycle phase, suggesting that these
      changes resulted directly from CSK disruption rather than from a general cell
      cycle block. Together, these data indicate the existence of a distinct time
      window in late G(1) in which signals elicited by the CSK act independently of
      early MAPK/Erk signals to drive the cell cycle machinery through the G(1)/S
      boundary and, hence, promote cell growth.

PMID- 11969295
TI  - A quantitative morphometric comparative analysis of the primate temporal lobe.
AB  - Given their importance in language comprehension, the human temporal lobes and/or
      some of their component structures might be expected to be larger than allometric
      predictions for a nonhuman anthropoid brain of human size. Whole brain, T1
      weighted MRI scans were collected from 44 living anthropoid primates spanning 11
      species. Easyvision software (Philips Medical Systems, The Netherlands) was used
      to measure the volume of the entire brain, the temporal lobes, the superior
      temporal gyri, and the temporal lobe white matter. The surface areas of both the
      entire temporal lobe and the superior temporal gyrus were also measured, as was
      temporal cortical gyrification. Allometric regressions of temporal lobe
      structures on brain volume consistently showed apes and monkeys to scale along
      different trajectories, with the monkeys typically lying at a higher elevation
      than the apes. Within the temporal lobe, overall volume, surface area, and white
      matter volume were significantly larger in humans than predicted by the ape
      regression lines. The largest departure from allometry in humans was for the
      temporal lobe white matter volume which, in addition to being significantly
      larger than predicted for brain size, was also significantly larger than
      predicted for temporal lobe volume. Among the nonhuman primate sample, Cebus have
      small temporal lobes for their brain size, and Macaca and Papio have large
      superior temporal gyri for their brain size. The observed departures from
      allometry might reflect neurobiological adaptations supporting species-specific
      communication in both humans and old world monkeys.

PMID- 11969296
TI  - The micromammalian fauna from the Leilao, Yuanmou hominoid locality: implications
      for biochronology and paleoecology.
AB  - The discovery of Lufengpithecus at Yuanmou, in Yunnan Province, China, provides
      important clues to understanding the evolution of early hominoids in eastern
      Asia. However, the age and paleoecology of the fauna remain to be established. An
      assemblage of micromammalian fossils, collected recently by screenwashing at
      Leilao, one of the hominoid-bearing localities at Yuanmou, contains 41 species
      belonging to 16 families and 4 orders, and represents the most diverse Neogene
      micromammalian fauna known from southwestern China. This paper presents an
      analysis of the taxonomy, age, and paleoecology of the micromammalian fauna. The
      Yuanmou hominoid fauna is now considered older than the Lufeng fauna, and is
      currently thought to correspond to an age of about 9 Ma. The micromammalian fauna
      indicates a predominantly forested habitat, with marginal environments consisting
      of bush-grassland.

PMID- 11969297
TI  - Patterns of cranial shape variation in the Papionini (Primates: Cercopithecinae).
AB  - Traditional classifications of the Old World monkey tribe Papionini (Primates:
      Cercopithecinae) recognized the mangabey genera Cercocebus and Lophocebus as
      sister taxa. However, molecular studies have consistently found the mangabeys to
      be diphyletic, with Cercocebus and Mandrillus forming a clade to the exclusion of
      all other papionins. Recent studies have identified cranial and postcranial
      features which distinguish the Cercocebus-Mandrillus clade, however the detailed
      similarities in cranial shape between the mangabey genera are more difficult to
      reconcile with the molecular evidence. Given the large size differential between
      members of the papionin molecular clades, it has frequently been suggested that
      allometric effects account for homoplasy in papionin cranial form. A combination
      of geometric morphometric, bivariate, and multivariate methods was used to
      evaluate the hypothesis that allometric scaling contributes to craniofacial
      similarities between like-sized papionin taxa. Patterns of allometric and size
      independent cranial shape variation were subsequently described and related to
      known papionin phylogenetic relationships and patterns of development. Results
      confirm that allometric scaling of craniofacial shape characterized by positive
      facial allometry and negative neurocranial allometry is present across adult
      papionins. Pairwise comparisons of regression lines among genera revealed
      considerable homogeneity of scaling within the Papionini, however statistically
      significant differences in regression lines also were noted. In particular,
      Cercocebus and Lophocebus exhibit a shared slope and significant vertical
      displacement of their allometric lines relative to other papionins. These
      findings give no support to narrowly construed hypotheses of uniquely shared
      patterns of allometric scaling, either between sister taxa or across all
      papionins. However, more general allometric trends do appear to account for a
      substantial proportion of papionin cranial shape variation, most notably in those
      features which have influenced traditional morphological phylogenies. Examination
      of size-uncorrelated shape variation gives no clear support to molecular
      phylogenies, but underscores the absence of morphometric similarities between the
      mangabey genera when size effects are controlled. Patterns of allometric and size
      uncorrelated shape variation indicate conservatism of cranial form in non-
      Theropithecus papionins, and suggest that Papio represents the primitive
      morphometric pattern for the African papionins. Lophocebus exhibits a divergent
      morphometric pattern, clearly distinguishable from other papionins, most notably
      Cercocebus. These results clarify patterns of cranial shape variation among the
      extant Papionini and lay the groundwork for studies of related fossil taxa.

PMID- 11969298
TI  - Taxonomic variation in the patterns of craniofacial dimorphism in primates.
AB  - Understanding sexual dimorphism in living primates is important for interpreting
      the biological and taxonomic significance of variation in the primate fossil
      record. In the past two decades, there has been an increasing emphasis on the
      fact that sexual dimorphism varies in both magnitude and pattern among species.
      Several studies have suggested that distinct patterns of dimorphism may assist in
      species recognition and perhaps phylogenetic analysis. This study evaluates
      patterns of craniofacial dimorphism in samples of 82 anthropoid primates.
      Dimensions of the viscerocranium tend to be more dimorphic than those of the
      neurocranium and orbits. Principal components analysis of phylogenetically
      controlled data demonstrates a basic pattern of dimorphism in overall skull
      proportions, and a distinction between length and breadth measurements. For any
      given species there can be substantial variation in the magnitude of dimorphism
      among dimensions, and different species can show substantially different patterns
      of dimorphism within and between regions of the skull and jaws. Patterns of
      dimorphism are clearly associated with phylogeny. Pattern similarity is not
      dependent on the overall magnitude of craniofacial dimorphism, or body mass
      dimorphism. Among all anthropoids, there are few combinations of characters that
      consistently show greater or lesser degrees of dimorphism. Such "stability" of
      patterns increases within genera. Patterns of dimorphism are likely to be useful
      for interpreting the taxonomic significance of variation in the fossil record.
      However, phylogenetic propinquity alone is not reason to use an extant species as
      a model for variation in an extinct species. Rather, care must be taken to
      identify stable patterns of dimorphism within a group of closely related extant
      species.

PMID- 11969299
TI  - Another look at shape variation in the distal femur of Australopithecus
      afarensis: implications for taxonomic and functional diversity at Hadar.
AB  - Previous studies have recognized two patterns of distal femoral morphology among
      the specimens from Hadar (Ethiopia) assigned to Australopithecus afarensis. Size
      and shape differences between the well-preserved large (AL 333-4) and small (AL
      129-1a) distal femora have been used to invoke both taxonomic and functional
      differences within the A. afarensis hypodigm. Nevertheless, prior studies have
      not analyzed these specimens in a multivariate context, nor have they compared
      the pattern of shape differences between the fossils to patterns of sexual
      dimorphism among extant taxa (i.e., the manner in which males and females
      differ). This study reexamines morphometric differences between the above
      specimens in light of observed levels of variation and patterns of sexual
      dimorphism among extant hominoids. Eight extant reference populations were
      sampled to provide a standard by which to consider size and shape differences
      between the fossils. Samples include three populations of modern humans, two
      subspecies of Pan troglodytes, three subspecies of Gorilla gorilla, Pan paniscus,
      and Pongo pygmaeus. Using size ratios and scale-free "shape" data (both derived
      from 2-D coordinate landmarks), size and shape differences between the fossils
      were evaluated against variation within each reference population using an exact
      randomization procedure. Growth Difference Matrix Analysis (GDMA) was used to
      test whether the pattern of morphological differences between the fossils differs
      significantly from patterns of sexual dimorphism observed among the ten extant
      groups. Overall morphometric affinities of the fossils to extant taxa were
      explored using canonical variates analysis (CVA). Results of the randomization
      tests indicate that the size difference between the Hadar femora can be easily
      accommodated within most hominoid taxa at the subspecific level (though not
      within single-sex samples). In addition, the magnitude of shape differences
      between the fossils can be commonly sampled even within most single-sex samples
      of a single hominoid subspecies. The pattern of morphological differences between
      the fossils does not differ statistically from any average pattern of femoral
      shape dimorphism observed among living hominoids. Moreover, contrary to prior
      claims, and despite a size disparity between the fossils greater than is
      typically observed within some chimpanzee and human populations, the two Hadar
      fossils appear to be much more similar to one another in overall shape than
      either specimen is to any extant hominoid group.

PMID- 11969300
TI  - Within-group human variation in the Asian Pleistocene: the three Upper Cave
      crania.
AB  - Numerous studies on Pleistocene samples have shown that within-group cranial
      variation was greater than that seen today. The three anatomically modern Upper
      Cave crania (UC 101, UC 102, and UC 103) from Zhoukoudian, China provide one of
      the best samples available for addressing the issue of the antiquity of the
      modern pattern of within-group cranial variability because archaeological
      evidence indicates that they are spatially and temporally restricted. Research on
      the Upper Cave fossils usually only includes UC 101 and UC 103 because of
      postmortem damage to UC 102's cranial vault. However, the face of UC 102 is
      undamaged, allowing for most facial measurements to be performed accurately. In
      this study we use facial dimensions to compare all three Upper Cave specimens,
      and we evaluate whether the variation seen among them is larger than that
      observed in extant populations. Using a worldwide sample of modern populations to
      establish a baseline, the three Upper Cave crania were compared to each other.
      Since there is disagreement over the sex of UC 102, this specimen is treated
      alternately as a female and as a male. Results show that the Upper Cave specimens
      exhibit significantly more variation than do individuals within more recent human
      populations, especially if UC 102 is considered male. Furthermore, results
      indicate that the fossils never fall into the same modern human group, and that
      each specimen is significantly atypical of its nearest modern neighbor in
      multivariate space. We conclude that the three Upper Cave crania do not represent
      a family group but are representative of the larger contemporaneous heterogeneous
      Asian Pleistocene population. Our results support the contention that today's
      within-group homogeneity is a relatively recent phenomenon, and is likely the
      result of a Neolithic population expansion and its many effects.

PMID- 11969302
TI  - Microvascular abnormalities in pediatric diabetic patients.
AB  - Microvascular abnormalities are associated with and causative of the development
      of end-stage organ complications in adult diabetic patients. Whether the same
      microvascular abnormalities are present in pediatric patients is not known and
      has not been studied because of a lack of real-time technology, methodology to
      study young patients, and availability of an appropriate noninvasive site for in
      vivo studies. We hypothesized that microvascular abnormalities should be present
      in pediatric patients despite their young age and the relatively short durations
      of the disease. In this study, computer-assisted intravital microscopy (CAIM) was
      adapted to blindly quantify microvascular abnormalities in 12 pediatric type 1
      diabetic mellitus (T1DM) patients (ages = 6-16 years; mean +/- SD = 11.42 +/-
      3.42; duration since diagnosis = 2-14 years; mean +/- SD = 6.75 +/- 3.79) in
      vivo, using the microcirculation of the bulbar conjunctiva as a noninvasive site.
      Microvascular abnormalities, commonly found in adult patients, existed in the
      conjunctival microcirculation of all pediatric T1DM patients in varying degrees
      despite their relatively young age. A severity index (SI) was developed to
      reflect the cumulative severity of the microvascular abnormalities and was
      computed as the summation of all microvascular abnormalities found in each
      patient. SI for the 12 T1DM patients (mean +/- SD = 7.42 +/- 1.88; median = 8;
      mode = 9) differed significantly from that for the nondiabetic controls (mean +/-
      SD = 0.67 +/- 0.78; median = 0.5; mode = 0; P < 0.0001). In addition, SI
      correlated with hemoglobin A1c levels (mean +/- SD = 9.18 +/- 1.57) of T1DM
      patients but did not correlate with the duration of disease since diagnosis of
      the same patients. This observation raises the possibility that diabetic
      pathogenesis may precede the onset of overt disease or clinical diagnosis. This
      study confirms that CAIM may represent the availability of a useful real-time
      technology to study conjunctival microvascular abnormalities in vascular diseases
      in juvenile as well as adult patients.

PMID- 11969301
TI  - Microvascular endothelial cells differ in basal and hypoxia-regulated expression
      of angiogenic factors and their receptors.
AB  - Phenotypically and functionally different types of microvascular endothelial
      cells (MVECs) derived from the developing corpus luteum were isolated and
      characterized by our group. We investigated whether these cytokeratin-positive
      (CK+) and cytokeratin-negative (CK-) MVECs differed in the expression of
      angiogenic factors and their regulation under hypoxia. Using quantitative RT-PCR,
      VEGF and its receptors, Flk-1 and Flt-1, were detected in CK- MVECs. The mRNA
      expression of Flk-1 mRNA was 100 times as high as that of Flt-1 mRNA. CK+ MVECs
      expressed VEGF and Flt-1 mRNA, but were devoid of Flk-1 transcripts. No Ang-1
      mRNA was demonstrated in either cell type, and Ang-2 mRNA was found only in CK-
      MVECs. Tie-2 mRNA was detected in both MVEC types, but levels were 150 times as
      high in CK- MVECs as in CK+ MVECs. mRNA of hypoxia-inducible factors Hif-1alpha
      and Hif-1beta was expressed in both MVEC types. After hypoxia, neither VEGF, nor
      Flk-1, nor Tie-2 mRNA expression was altered in either MVEC type. Flt-1
      expression and Ang-2 mRNA expression were significantly increased at about 2.5
      fold (P < 0.05) in CK- MVECs, but not in CK+ MVECs. Our study demonstrates the
      varying expression and regulation of angiogenesis-related factors and receptors
      in phenotypically different MVEC types.

PMID- 11969303
TI  - Extracellular angio-associated migratory cell protein plays a positive role in
      angiogenesis and is regulated by astrocytes in coculture.
AB  - The extracellular form of angio-associated migratory cell protein (AAMP), a
      recently discovered protein, plays a positive role in angiogenesis and can be
      regulated by astrocytes. Angiogenic activities are inhibited by an affinity
      purified, polyclonal antibody generated to recombinant AAMP. Inhibition of
      endothelial cell tube formation was previously shown and now endothelial cell
      migration assays using this antibody show dose-dependent inhibition (75%) of
      endothelial cell migration. Also, antisense inhibition has been used to determine
      the effects of reducing total AAMP (extracellular and intracellular forms). An
      AAMP-specific antisense oligonucleotide that targets a region near its amino
      terminus, anti-MES, inhibits (45%) total AAMP production by bovine aortic
      endothelial cells (BAECs), compared to a negative control oligonucleotide.
      Paradoxically, comparable use of antisense-MES results in a 27% increase in BAEC
      motility. Decreased cellular production of total AAMP (via antisense) that
      results in an increase of endothelial migration contrasts with antibody
      inhibition of extracellular AAMP that decreases migration. This indicates
      compartment-specific roles for AAMP in angiogenesis. Transwell cocultures of
      human astrocytes and BAECs increase (53%) the amount of extracellular AAMP found
      associated with endothelial cells. Therefore, regulation of extracellular AAMP by
      astrocytes is hypothesized to aid in angiogenesis of the nervous system.
      Extracellular AAMP's positive role may be either as a promoter or as a permissive
      protein in this process.

PMID- 11969304
TI  - The feasibility and reliability of capillary blood pressure measurements in the
      fingernail fold.
AB  - Capillary blood pressure is an essential parameter in the study of the (patho
      )physiology of microvascular perfusion. Currently, capillary pressure
      measurements in humans are performed using a servo-nulling micropressure system
      containing an oil-water interface, which suffers some drawbacks. In addition, the
      effect of the preparation of the skin and the presence of the tip of the pipette
      in the capillary during the measurement on microcirculatory perfusion has never
      been described. Therefore, we assessed the feasibility of capillary pressure
      measurements using an alternative micropressure system using an air-water
      interface (900 A, WPI) and examined the effect of the measurement on local
      microcirculation. In 19 healthy male volunteers the apex of capillaries in the
      eponychium of the fourth finger was punctured, after skin peeling, by a
      micropipette connected to a servo-nulling micropressure system. Red blood cell
      velocity (RBCV) was assessed after peeling during the measurement and at an
      adjacent area. Mean capillary pressure (in 16/19 volunteers) was 20.5 +/- 3.7 mm
      Hg (systolic 26.2 +/- 5.6 mm Hg, diastolic 17.6 +/- 3.9 mm Hg). RBCV was not
      significantly different before (0.52 mm/s) and during the measurement (0.51 mm/s)
      and at an adjacent area (0.51 mm/s). Capillary pressure can be measured well with
      the alternative setup used without hampering capillary flow, while the pressures
      obtained are in agreement with the results reported previously by other
      investigators.

PMID- 11969305
TI  - A technique for quantitative three-dimensional analysis of microvascular
      structure.
AB  - Research into angiogenesis and vascular microarchitecture has contributed to
      progress in a wide variety of biomedical fields, but increased understanding is
      limited, in part, by the available assays and imaging modalities. Techniques that
      allow quantitation of vascular microarchitecture are needed. A comprehensive
      method is presented that uses 6-microm-thick serial sections of frozen tissue
      samples, immunostaining for CD31, brightfield microscopy, automated alignment of
      two-dimensional serial sections, and volume rendering to produce high-resolution,
      three-dimensional, quantifiable images of microvascular structure. Application of
      the technique is shown by characterizing vascularization into a fibrin gel
      implanted against the skeletal muscle of rats and explanted after 7 days.
      Comparing measurements from automated and manually aligned MRI and fibrin samples
      verified quantitation. Automation removes concerns of observer bias or variation
      inherent in manual alignment and increases the speed of analysis. Analysis of the
      fibrin gel reveals a dense (4.3 +/- 1.1% endothelial cell density) network of
      tortuous (1.37 +/- 0.05 tortuosity) capillaries that replaces the gel as it
      degrades. There is a high level of void space (22.8 +/- 3.6%) in the gel, and
      average capillary length in the fibrovascular tissue was 93.0 +/- 7.4 microm.
      Data obtained from these automatically aligned images agreed with those obtained
      using manual analysis (no statistical difference), and the results are consistent
      with data from traditional methods.

PMID- 11969306
TI  - Morphoangiogenesis: a unique action of growth hormone.
AB  - A new form of angiogenesis, morphoangiogenesis (M-A), produces stem cells in vivo
      in adults. M-A was first identified in the knees of adult rabbits used to test
      intraarticular growth hormone (IAGH) injections as a method of regenerating
      articulophyseal cartilage (APC). M-A produces two structures capable of
      generating the stem cells. The first structure, which resembles cartilage canals
      normally observed only in fetuses, starts to develop 24 h after an IAGH
      injection. The second structure, which resembles renal glomeruli, develops
      several weeks later. Both structures contained thin-walled fenestrated
      capillaries and produced stem cells which contributed to the cascade generating
      articular cartilage. It was thought that other uses for morphoangiogenesis could
      be developed. These include tissue and organ formation using stem cells produced
      by M-A and the obstruction of neovascularization of cancers by M-A's ability to
      form structures which would obstruct nutritive vessels and thereby starve tumors.

PMID- 11969308
TI  - Comparative analysis of in vitro angiogenic activities of endothelial cells of
      heterogeneous origin.
AB  - Endothelial cells are dynamic participants in many aspects of host defense,
      innate immunity, inflammation, angiogenesis, and vasculogenesis, but the
      interpretation of studies of their responses is often clouded by the source of
      the cells under observation. Thus, it is not clear which endothelial cell type
      should be utilized in in vitro studies to clarify the basis and physiological
      relevance of essential processes, including chemotactic migration and morphogenic
      differentiation. In this study, we compared responses of endothelial cells of a
      variety of origins, as well as an immortalized cell line, using both protein
      growth factors and biologically active lipid mediators as agonists. While cells
      of divergent origin displayed marked differences in the extent of their
      responsiveness, with a few notable exceptions, their pattern of responsiveness to
      receptor-dependent stimuli was remarkably similar. Moreover, even the
      immortalized endothelial cell line Py-4-l migrated in a pattern consistent to
      that seen with primary cells in culture although the immortalized cells failed to
      form capillarylike structures under any of the conditions tested. We conclude
      that although the immortalized endothelial cell line Py-4-l is not appropriate
      for investigations of endothelial cell morphogenic responses, cultured cells from
      other sources, including arteries, veins, and capillaries, often provide
      qualitatively similar results to divergent metabolic stimuli.

PMID- 11969307
TI  - Inhibition of vascular endothelial growth factor-associated tyrosine kinase
      activity with SU5416 blocks sprouting in the microvascular endothelial cell
      spheroid model of angiogenesis.
AB  - The angiogenic vascular endothelial growth factor (VEGF) is believed to play a
      critical role in endothelial cell proliferation, differentiation, and sprouting.
      Small molecules that selectively inhibit the VEGF receptor-associated tyrosine
      kinase activities of Flk-1 (KDR) and Flt-1 have been developed. These agents, a
      prototype being SU5416, have effects on the proliferation of cultured endothelial
      cells, constrain angiogenesis in vivo, and have been proposed as antitumor drugs.
      Although SU5416 inhibits in vivo angiogenesis, it is not clear which of the
      complex processes leading to angiogenesis are impacted by VEGF receptor
      associated tyrosine kinase inhibition. We utilized SU5416 and a microvascular
      endothelial cell line derived from mouse heart (SMHEC4) to specifically examine
      the role of VEGF receptor-associated tyrosine kinase activity on in vitro models
      of angiogenesis. We characterized spheroid formation and sprouting, a new model
      of angiogenesis, in this stable cell line. SU5416 inhibits (approximately 50%)
      VEGF (50 ng/ml) stimulated and basal DNA synthesis of SMHEC4 cultured in
      monolayer. SU5416 does not prevent the aggregation and organization of SMHEC4
      into tri-dimensional spheroids. CD31, a marker of differentiated endothelial
      cells, is negligibly expressed in monolayer cultures but highly expressed in
      SMHEC4 spheroids. The content and biochemical characteristics of spheroidal CD31
      are unaltered by SU5416. SU5416 also does not prevent the spontaneous and rapid
      (approximately 3-h) alignment into cords by SMHEC4 on Matrigel. These two models
      suggest that the organization and differentiation of endothelial cells is
      independent of VEGF receptor-associated tyrosine kinase signaling. SMHEC4
      spheroids embedded in collagen gels spontaneously and rapidly (approximately 6 h)
      sprout capillary-like projections and subsequently (1-2 days) form complex self
      anastomosing networks. In addition, VEGF (50 ng/ml) markedly stimulates sprouting
      of capillary-like projections from SMHEC4 spheroids. Both the spontaneous and the
      VEGF-stimulated sprouting are nearly eliminated by SU5416. This demonstrates that
      VEGF receptor-associated tyrosine kinase activity is essential to the formation
      of capillary-like structures from SMHEC4 spheroids. Overall, these observations
      demonstrate that (a) the spheroid sprouting model is appropriate for the study of
      angiogenesis since it appears to recapitulate many of its steps and (b) SU5416
      can inhibit endothelial cell proliferation and sprouting without impacting the
      organization and differentiation of endothelial cells.

PMID- 11969309
TI  - LEX032, a novel recombinant serpin, protects the brain after transient focal
      ischemia.
AB  - This investigation examined the effectiveness of a serine protease inhibitor
      (LEX032) when used as a cerebral protective agent after ischemia. Focal cerebral
      ischemia in the rat was produced by intravascular occlusion of the middle
      cerebral artery for a period of 30 min. Just prior to thread withdrawal (i.e.,
      reperfusion), rats received an iv bolus administration of either vehicle or
      LEX032 (50 mg/kg), an optimal dose chosen based on previous studies.
      Somatosensory evoked potentials (SSEP's) were monitored prior to, during, and for
      a period of 60 min after removal of occlusion. The animals were allowed to
      recover for 24 h after the ischemic insult. Cortical activity in the occluded
      region, as assessed by SSEPs, returned much sooner in the LEX032-treated animals
      (10 +/- 6 min) than in the untreated animals (40 +/- 25 min). On a scale ranging
      from 0 to 3, with three indicating the most severely injured, the LEX032 animals
      had a significantly better neurologic score (1.0 +/- 0.9) than the untreated
      animals (2.3 +/- 0.5) 24 h after ischemia. The improved neurobehavior was related
      to a 55% reduction in brain injury as assessed by TTC staining. LEX032-treated
      animals had significantly (P < 0.01) smaller infarcts (115 +/- 40 mm3) compared
      to vehicle-treated animals (263 +/- 13 mm3). In a separate group of animals (n =
      6/group), leukocyte infiltration, as evaluated by tissue myeloperoxidase activity
      (MPO U/g tissue wt), was also significantly (P < 0.05) lower in the LEX032
      treated animals (1.4 +/- 0.3) compared to vehicle-treated animals (3.6 +/- 0.7).
      This data demonstrates that LEX032 reduces brain injury and suggests that serine
      protease inhibitors may reduce ischemia/reperfusion injury by decreasing
      leukocyte activation and migration.

PMID- 11969310
TI  - Development of a computer-assisted high-throughput screening platform for anti
      angiogenic testing.
AB  - Angiogenesis is widely accepted to play a central role in tumor growth and
      spreading. Therefore, anti-angiogenic agents appear as promising tools in cancer
      therapy, and great efforts have been devoted to their identification in recent
      years. Despite fast progress in this area, a quantitative and objective system
      for rapid anti-angiogenic testing is not currently available. In this work, we
      describe a new platform for the large-scale screening of agents with potential
      anti-angiogenic activity. This involved the miniaturization of an in vitro two
      dimensional assay model of vascular morphogenesis to run in a high-density format
      (384- or 1536-well microplates) and the development of a specific digital image
      analysis system for the automated and quantitative evaluation of biological
      activity. To test the efficacy and reproducibility of the platform, we used a
      wide variety of well-characterized angiogenesis inhibitors, including antibodies
      against components of the extracellular matrix, peptides, and chemicals. The
      system proved to be a reproducible, polyvalent, and powerful tool for massive
      screening of agents with potential application in cancer therapy. Ongoing
      developmental work, directed toward optimizing this system for use with a fully
      automated high-throughput screening platform, should accelerate research into the
      mechanisms of tumor angiogenesis and the development of drugs that target the
      essential tumor vasculature.

PMID- 11969311
TI  - Parenchymal tissue cytochrome P450 4A enzymes contribute to oxygen-induced
      alterations in skeletal muscle arteriolar tone.

PMID- 11969312
TI  - Effects of image resolution on autoradiographic measurements of posterior
      cingulate activity in PDAPP mice: implications for functional brain imaging
      studies of transgenic mouse models of Alzheimer's Disease.
AB  - Fluorodeoxyglucosepositron emission tomography (PET) studies find that persons
      with Alzheimer's disease have preferential reductions in posterior cingulate
      activity. Using fluorodeoxyglucose autoradiography, we found that transgenic mice
      overexpressing a mutant form of the human amyloid precursor protein have
      preferentially reduced activity in the same region, providing a potential brain
      imaging indicator of Alzheimer's disease in these animals. In this study, we
      considered the feasibility of using in vivo imaging techniques, such as PET, to
      detect this reduction despite their limitations in spatial resolution.
      Autoradiographic measurements of posterior cingulate activity were remeasured in
      the previously studied PDAPP transgenic and littermate control mice after the
      images were filtered to lower spatial resolutions. We continued to detect
      significantly lower cingulate activity in the transgenic mice when the images
      were blurred to 0.50 mm, failed to detect significantly abnormal activity when
      the images were blurred to 0.75 mm, and, indeed, found significantly higher
      activity when the images were blurred to 1.0 mm. Reversal in direction of the
      abnormality appears attributable to a previously observed truncation in the
      corpus callosum in PDAPP mice. With the possible exception of future in vivo
      imaging techniques that have a spatial resolution greater than or equal to 0.50
      mm and high sensitivity, noninvasive functional brain imaging techniques like PET
      may not be suitable for detecting declines in regional activity in PDAPP mice. It
      remains possible that these imaging techniques will prove useful in transgenic
      mouse lines that do not exhibit the same morphological abnormalities in
      neighboring white matter regions.

PMID- 11969313
TI  - Functional anatomy of intra- and cross-modal lexical tasks.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine lexical
      processing in normal adults (20-35 years). Two tasks required only intramodal
      processing (spelling judgments with visual input and rhyming judgments with
      auditory input) and two tasks required cross-modal processing between phonologic
      and orthographic representations (spelling judgments with auditory input and
      rhyming judgments with visual input). Each task led to greater activation in the
      unimodal association area concordant with the modality of input, namely fusiform
      gyrus (BA 19, 37) for written words and superior temporal gyrus (BA 22, 42) for
      spoken words. Cross-modal tasks generated greater activation in posterior
      heteromodal regions including the supramarginal and angular gyri (BA 40, 39).
      Cross-modal tasks generated additional activation in unimodal areas representing
      the target of conversion, superior temporal gyrus for visual rhyming and fusiform
      gyrus for auditory spelling. Our findings suggest that the fusiform gyrus
      processes orthographic word forms, the superior temporal gyrus processes
      phonologic word forms, and posterior heteromodal regions are involved in the
      conversion between orthography and phonology.

PMID- 11969314
TI  - Voxel-based morphometric comparison of hippocampal and extrahippocampal
      abnormalities in patients with left and right hippocampal atrophy.
AB  - We used voxel-based morphometry (VBM), an automatic whole-brain MR image analysis
      technique, to investigate gray matter abnormalities in patients with temporal
      lobe epilepsy (TLE), in whom hippocampal atrophy (HA) was demonstrated by
      application of the Cavalieri method of modern design stereology. VBM results (P <
      0.05, corrected) indicated preferential gray matter concentration (GMC) reduction
      in anterior hippocampus in patients with left HA and posterior hippocampus in
      patients with right HA. GMC reduction was also found in right dorsal prefrontal
      cortex in left and right HA patients. Prefrontal atrophy may be due to
      epileptiform excitotoxic discharges from the reciprocally connected pathological
      hippocampus, and may be the underlying biological cause for executive dysfunction
      in patients with TLE. GMC excess in ipsilateral parahippocampal, cerebellar, and
      pericallosal regions was common to both left and right HA groups relative to
      controls, and is hypothesized to reflect diminished gray-white matter
      demarcation, underlying white matter atrophy, or structural displacement due to
      cerebrospinal fluid expansion. However, bilateral temporal lobe GMC excess was
      observed in left HA patients, while ipsilateral temporal lobe GMC excess was
      observed in right HA patients. This work demonstrates methodological consistency
      between automated VBM and manual stereological analysis of the hippocampus in
      group comparisons, indicates widespread extrahippocampal gray matter
      abnormalities in unilateral HA, and suggests that there may be inherent
      differences in the effect of TLE on temporal lobe structures depending on the
      side of HA.

PMID- 11969315
TI  - Simultaneous EEG-Correlated Ictal fMRI.
AB  - The ability to continuously acquire simultaneous EEG and fMRI data during
      seizures presents a formidable challenge both clinically and technically.
      Published ictal fMRI reports have so far been unable to benefit from simultaneous
      electrographic recordings and remain largely assumptive. Unique findings from a
      Continuous EEG-correlated fMRI experiment are presented in which a focal
      subclinical seizure was captured in its entirety. For the first time dynamic and
      biphasic Blood Oxygen Level Dependent (BOLD) signal changes are shown using
      statistical parametric mapping time-locked to the ictal EEG activity localizing
      seizure generation and propagation sites, with millimeter resolution, to
      electroclinically concordant gray matter structures. Though presently of limited
      clinical applicability, a new avenue is opened for further research.

PMID- 11969316
TI  - Millisecond by millisecond, year by year: normative EEG microstates and
      developmental stages.
AB  - Most studies of continuous EEG data have used frequency transformation, which
      allows the quantification of brain states that vary over seconds. For the
      analysis of shorter, transient EEG events, it is possible to identify and
      quantify brain electric microstates as subsecond time epochs with stable field
      topography. These microstates may correspond to basic building blocks of human
      information processing. Microstate analysis yields a compact and comprehensive
      repertoire of short lasting classes of brain topographic maps, which may be
      considered to reflect global functional states. Each microstate class is
      described by topography, mean duration, frequency of occurrence and percentage
      analysis time occupied. This paper presents normative microstate data for resting
      EEG obtained from a database of 496 subjects between the age of 6 and 80 years.
      The extracted microstate variables showed a lawful, complex evolution with age.
      The pattern of changes with age is compatible with the existence of developmental
      stages as claimed by developmental psychologists. The results are discussed in
      the framework of state dependent information processing and suggest the existence
      of biologically predetermined top-down processes that bias brain electric
      activity to functional states appropriate for age-specific learning and behavior.

PMID- 11969317
TI  - A fully automated method for tissue segmentation and CSF-correction of proton
      MRSI metabolites corroborates abnormal hippocampal NAA in schizophrenia.
AB  - In this report, we describe the implementation and application of a fully
      automated segmentation routine using SPM99 algorithms and MATLAB for clinical
      Magnetic Resonance Spectroscopic Imaging (MRSI) studies. By segmenting high
      resolution 3-D image data and coregistering the results to the spatial localizer
      slices of a spectroscopy examination, the program offers the possibility to
      easily calculate segmentation maps for a large variety of MRSI experiments. The
      segmented data are corrected for the individual point-spread function, slice and
      VOI profiles for measurement sequences with selective pulses as well as for the
      chemical shifts of different metabolites. The new method was applied to
      investigate discrete hippocampal metabolite abnormalities in a small sample of
      schizophrenic patients in comparison to healthy controls (15 patients, 15
      controls). Only after correction was the N-acetyl-aspartate (NAA) signal
      significantly lower in patients compared to controls. No differences were found
      for the corrected signals from the creatine/phosphocreatine (Cr) or choline
      containing compounds (Ch). These results are in good agreement with
      neuropathological and previous MR spectroscopy studies of the hippocampus in
      schizophrenic patients.

PMID- 11969318
TI  - A developmental fMRI study of the Stroop color-word task.
AB  - We used fMRI to investigate developmental changes in brain activation during a
      Stroop color-word interference task. A positive correlation was observed between
      age and Stroop-related activation (n = 30) in the left lateral prefrontal cortex,
      the left anterior cingulate, and the left parietal and parieto-occipital
      cortices. No regions showed a negative correlation between activation and age. We
      further investigated age-related differences by stratifying the sample into three
      age groups: children (ages 7-11), adolescents (ages 12-16), and young adults
      (ages 18-22). Young adult subjects (n = 11) displayed significant activation in
      the inferior and middle frontal gyri bilaterally, the left anterior cingulate,
      and bilateral inferior and superior parietal lobules. Between-group comparisons
      revealed that young adults had significantly greater activation than adolescent
      subjects (n = 11) in the left middle frontal gyrus and that young adults showed
      significantly greater activation than children (n = 8) in the anterior cingulate
      and left parietal and parieto-occipital regions, as well as in the left middle
      frontal gyrus. Compared to children, both adult and adolescent subjects exhibited
      significantly greater activation in the parietal cortex. Adult and adolescent
      groups, however, did not differ in activation for this region. Together, these
      data suggest that Stroop task-related functional development of the parietal lobe
      occurs by adolescence. In contrast, prefrontal cortex function contributing to
      the Stroop interference task continues to develop into adulthood. This
      neuromaturational process may depend on increased ability to recruit focal neural
      resources with age. Findings from this study, the first developmental fMRI
      investigation of the Stroop interference task, provide a template with which
      normal development and neurodevelopmental disorders of prefrontal cortex function
      can be assessed.

PMID- 11969319
TI  - Segregated processing of auditory motion and auditory location: an ERP mapping
      study.
AB  - Recent studies have revealed a distinct cortical network activated during the
      analysis of sounds' spatial properties. Whether common brain regions in this
      auditory where pathway are involved in both auditory motion and location
      processing is unresolved. We investigated this question with multichannel
      auditory evoked potentials (AEPs) in 11 subjects. Stimuli were binaural 500-ms
      white noise bursts. Interaural time differences (ITD) created the sensation of
      moving or stationary sounds within each auditory hemifield, and subjects
      discriminated either their position or direction of motion in a blocked design.
      Scalp potential distributions (AEP maps) differentiated electric field
      configurations across stimulus classes. The initial approximately 250-ms
      poststimulus yielded common topographies for both stimulus classes and
      hemifields. After approximately 250-ms, moving and stationary sounds engaged
      distinct cortical networks at two time periods, again with no differences
      observed between hemifields. The first ( approximately 250- to 350-ms
      poststimulus onset) was during stimulus presentation, and the second (
      approximately 550- to 900-ms poststimulus onset) occurred after stimulus offset.
      Distributed linear inverse solutions of the maps over the 250- to 350-ms time
      period revealed not only bilateral inferior frontal activation for both types of
      auditory spatial processing, but also strong right inferior parietal activation
      in the case of auditory motion discrimination. During the later 550-to 900-ms
      time period, right inferior parietal and bilateral inferior frontal activity was
      again observed for moving sounds, whereas strong bilateral superior frontal
      activity was seen in the case of stationary sounds. Collectively, the evidence
      supports the existence of partly segregated networks within the auditory where
      pathway for auditory location and auditory motion processing.

PMID- 11969320
TI  - Motion artifact in magnetic resonance imaging: implications for automated
      analysis.
AB  - Automated measures of cerebral magnetic resonance images (MRI) often provide
      greater speed and reliability compared to manual techniques but can be
      particularly sensitive to motion artifact. This study employed an automatic MRI
      analysis program that quantified regional gray matter volume and created images
      for verification and quality control. Motion artifact was assessed on each image
      and assigned a rating of none, mild, moderate, or severe. Greater motion artifact
      was associated with smaller gray matter volumes. Severity of motion artifact is
      an important, but often overlooked, consideration in the interpretation of
      automated MRI measures.

PMID- 11969321
TI  - Investigating cervical spinal cord structure using axial diffusion tensor
      imaging.
AB  - This study describes a new technique for Diffusion Tensor Imaging (DTI) that
      acquires axial (transverse) images of the cervical spinal cord. The DTI images
      depict axonal fiber orientation, enable quantification of diffusion
      characteristics along the spinal cord, and have the potential to demonstrate the
      connectivity of cord white matter tracts. Because of the high sensitivity to
      motion of diffusion-weighted magnetic resonance imaging and the small size of the
      spinal cord, a fast imaging method with high in-plane resolution was developed.
      Images were acquired with a single-shot EPI technique, named ZOOM-EPI (zonally
      magnified oblique multislice echo planar imaging), which selects localized areas
      and reduces artefacts caused by susceptibility changes between soft tissue and
      the adjacent vertebrae. Cardiac gating was used to reduce pulsatile flow
      artefacts from the surrounding cerebrospinal fluid. Voxel resolution was 1.25 x
      1.25 mm(2) in-plane with 5-mm slice thickness. Both the mean diffusivity (MD) and
      the fractional anisotropy (FA) indices of the cervical spinal cord were measured.
      The FA index demonstrated high anisotropy of the spinal cord with an average
      value of 0.61 +/- 0.05 (highest value of 0.66 +/- 0.03 at C3), comparable to
      white matter tracts in the brain. The diffusivity components parallel and
      orthogonal to the longitudinal axes of the cord were lambda( parallel) = (1648 +/
      123) x 10(-6) mm(2)s(-1) and lambda( perpendicular) = (570 +/- 47) x 10(-6)
      mm(2) s(-1), respectively. The high axial resolution allowed preliminary
      evaluation of fiber connectivity using the fast-marching tractography algorithm,
      which generated traces of fiber paths consistent with the well-known cord
      anatomy.

PMID- 11969322
TI  - Task-related changes in cortical synchronization are spatially coincident with
      the hemodynamic response.
AB  - Using group functional Magnetic Resonance Imaging (fMRI) and group
      Magnetoencephalography (MEG) we studied two cognitive paradigms: A language task
      involving covert letter fluency and a visual task involving biological motion
      direction discrimination. The MEG data were analyzed using an adaptive beam
      former technique known as Synthetic Aperture Magnetometry (SAM), which provides
      continuous 3-D images of cortical power changes. These images were spatially
      normalized and averaged across subjects to provide a group SAM image in the same
      template space as the group fMRI data. The results show that frequency-specific,
      task-related changes in cortical synchronization, detected using MEG, match those
      areas of the brain showing an evoked cortical hemodynamic response with fMRI. The
      majority of these changes were event-related desynchronizations (ERDs) in the 5
      10 Hz and 15-25 Hz frequency ranges. Our study demonstrates how SAM, spatial
      normalization, and intersubject averaging enable group MEG studies to be
      performed. SAM analysis also allows the MEG experiment to have exactly the same
      task design as the corresponding fMRI experiment. This new analysis framework
      represents an important advance in the use of MEG as a cognitive neuroimaging
      technique and also allows mutual cross-validation with fMRI.

PMID- 11969323
TI  - Brain activation sequences following electrical limb stimulation of normal and
      paraplegic subjects.
AB  - In current clinical practice the degree of paraplegia or quadriplegia is
      objectively determined with transcranial magnetic stimulation (TMS) and
      somatosensory-evoked potentials (SSEP). We measured the MEG signal following
      electrical stimulation of upper and lower limbs in two normal and three
      clinically complete paraplegic subjects. From the MEG signal we computed
      distributed estimates of brain activity and identified foci just behind the
      central sulcus consistent in location with primary somatosensory (SI) for arm and
      foot and secondary somatosensory (SII) areas. Activation curves were computed
      from regions of interest defined around these areas. Activation of the SI foot
      area was observed in normal and paraplegic subjects when the upper limb was
      stimulated. Surprisingly, for each paraplegic subject, stimulation below the
      lesion was followed by cortical activations. These activations were weak, only
      loosely time-locked to the stimulus and were seen intermittently behind the
      central sulcus and nearby cortical areas. Statistical analysis of tomographic
      solutions and activation curves showed consistent responses following foot
      stimulation in one paraplegic (PS1) and intermittently in another paraplegic
      subject. We repeated the same experiment for PS1 in a different laboratory and
      the results from the analysis of foot stimulation from both laboratories revealed
      statistically significant focal cortical response only in the contralateral SI
      foot area.

PMID- 11969324
TI  - Medium-range oscillatory network and the 20-Hz sensorimotor induced potential.
AB  - Although synchronously oscillating neuronal assemblies have been the subject of
      many studies, a clear identification of the spatiotemporal characteristics of a
      medium-range oscillatory network is still lacking. Herein, we present a method
      for the extraction of a new waveform, namely the mean induced potential (IP),
      which allows the identification of the spatiotemporal characteristics of induced
      EEG responses. The IP calculation was applied to the 20-Hz component of the
      sensorimotor rhythm in order to obtain a 20-Hz sensorimotor induced potential (20
      Hz SIP). The spatiotemporal characteristics of the 20-Hz bursts seen after median
      nerve stimulation and self-paced finger movements were extracted by means of
      current source density reconstruction and synchronization analysis. A cortical
      network including the controlateral primary motor cortex, the supplementary motor
      area, and the controlateral supramarginalis gyrus was found to generate the 20-Hz
      bursts, and the various activated areas were found to be highly synchronized. Our
      results demonstrate for the first time the existence of a medium-range cortical
      network in the human sensorimotor region whose constituents oscillate
      synchronously.

PMID- 11969325
TI  - Motor learning produces parallel dynamic functional changes during the execution
      and imagination of sequential foot movements.
AB  - The aim of the present positron emission tomography study was to measure the
      dynamic changes in cerebral activity before and after practice of an explicitly
      known sequence of foot movements when executed physically and to compare them to
      those elicited during motor imagery of the same movements. Nine healthy
      volunteers were scanned while performing both types of movement at an early phase
      of learning and after a 1-h training period of a sequence of dorsiflexions and
      plantarflexions with the left foot. These experimental conditions were compared
      directly, as well as to a perceptual control condition. Changes in regional
      cerebral blood flow associated with physical execution of the sequence early in
      the learning process were observed bilaterally in the dorsal premotor cortex and
      cerebellum, as well as in the left inferior parietal lobule. After training,
      however, most of these brain regions were no longer significantly activated,
      suggesting that they are critical for establishing the cognitive strategies and
      motor routines involved in executing sequential foot movements. By contrast,
      after practice, an increased level of activity was seen bilaterally in the medial
      orbitofrontal cortex and striatum, as well as in the left rostral portion of the
      anterior cingulate and a different region of the inferior parietal lobule,
      suggesting that these structures play an important role in the development of a
      long lasting representation of the sequence. Finally, as predicted, a similar
      pattern of dynamic changes was observed in both phases of learning during the
      motor imagery conditions. This last finding suggests that the cerebral plasticity
      occurring during the incremental acquisition of a motor sequence executed
      physically is reflected by the covert production of this skilled behavior using
      motor imagery.

PMID- 11969326
TI  - Cerebral responses to noxious thermal stimulation in chronic low back pain
      patients and normal controls.
AB  - Changes in regional cerebral blood flow (rCBF) have previously been demonstrated
      in a number of cortical and subcortical regions, including the cerebellum,
      midbrain, thalamus, lentiform nucleus, and the insula, prefrontal, anterior
      cingulate, and parietal cortices, in response to experimental noxious stimuli.
      Increased anterior cingulate responses in patients with chronic regional pain and
      depression to noxious stimulation distant from the site of clinical pain have
      been observed. We suggested that this may represent a generalized
      hyperattentional response to noxious stimuli and may apply to other types of
      chronic regional pain. Here these techniques are extended to a group of patients
      with nonspecific chronic low back pain. Thirty-two subjects, 16 chronic low back
      pain patients and 16 controls, were studied using positron emission tomography.
      Thermal stimuli, corresponding to the experience of hot, mild, and moderate pain,
      were delivered to the back of the subject's right hand using a thermal probe.
      Each subject had 12 measurements of rCBF, 4 for each stimulus. Correlation of
      rCBF with subjective pain experience revealed similar responses across groups in
      the cerebellum, midbrain (including the PAG), thalamus, insula, lentiform
      nucleus, and midcingulate (area 24') cortex. These regions represented the
      majority of activations for this study and those recorded by other imaging
      studies of pain. Although some small differences were observed between the groups
      these were not considered sufficient to suggest abnormal nociceptive processing
      in patients with nonspecific low back pain.

PMID- 11969327
TI  - Hemispheric lateralization effects of rhythm implementation during syllable
      repetitions: an fMRI study.
AB  - Rhythm in terms of the modulation of syllable durations represents an information
      bearing feature of verbal utterances contributing both to the meaning of a
      sentence (linguistic prosody) as well as a speaker's emotional expression
      (affective prosody). In order to delineate the neural structures subserving
      rhythmic shaping of speech production, functional magnetic resonance imaging
      (fMRI) was performed during (a) isochronous syllable repetitions and (b)
      production of syllable triplets with lengthening either of the initial or final
      unit. A cognitive subtraction approach (rhythmic versus isochronous iterations)
      revealed activation of right-sided perisylvian areas (superior temporal gyrus,
      Broca analogue and adjacent premotor cortex) as well as contralateral subcortical
      structures (putamen and thalamus). Presumably, these responses reflect a right
      hemisphere rehearsal mechanism of rhythmic patterns and left-hemisphere
      monitoring of verbal output.

PMID- 11969328
TI  - A model-based method for retrospective correction of geometric distortions in
      diffusion-weighted EPI.
AB  - The self-diffusion tensor may be calculated from several echo-planar image
      acquisitions preceded by different diffusion gradients. Unfortunately, these
      diffusion gradients cause geometric distortion that must be corrected before
      estimation of the tensor. In the present paper we suggest and implement a method
      for retrospective correction of these distortions firmly based on a physical
      model for the diffusion-weighted images. This method simultaneously estimates
      subject movement and distortion parameters by finding the set of parameters that
      minimizes residual error when fitting data to the diffusion tensor model. We show
      how this notion can be formalized as a quadratic form thereby facilitating the
      implementation of a rapid algorithm. In addition, we suggest models for how
      distortions vary with slice position and gradient direction that allow us to
      substantially reduce the dimensionality of the parameter space. Our results
      indicate that we are able to estimate both eddy current-induced distortion and
      subject movement directly from the data without need of any additional
      measurements.

PMID- 11969329
TI  - Experimental performance assessment of SPM for SPECT neuroactivation studies
      using a subresolution sandwich phantom design.
AB  - The validity domain of voxel-based statistical analysis of SPECT neuroactivation
      studies with statistical parametric mapping (SPM) has been investigated by a
      limited number of theoretical and simulation studies. In this work, an
      experimental setup is described with an assessment of its activation detection
      performance together with the influence of acquisition and processing parameters.
      A subresolution sandwich phantom was constructed using a printed high-resolution
      digital Hoffman phantom with a (99m)TcO(4)-ink mixture. Activations of 8, 16, and
      24 mm diameter, with an intensity ranging from 5 to 60%, were constructed in the
      right frontal cortex, anterior and posterior cingulate, and left striatum. Triple
      headed SPECT acquisitions were carried out using both fan-beam and parallel beam
      geometry. The impact of activation characteristics (size, intensity and
      location), study size, physical degradation factors, and reconstruction technique
      were studied using SPM99 in a group comparison design with correction for
      multiple comparisons. For a 15 x 15 design, all 24-mm activations of 5% intensity
      were detected for the fan-beam data. Decreased focus or study size, lower SPECT
      resolution, absence of scatter, and attenuation correction resulted in an
      increase in minimally detectable activation. For a single study referred to 15
      control studies, only 24-mm activation foci with a minimal intensity of 10% were
      detected in the optimal configuration. This approach allows experimental
      parameter optimization of SPM-based group or single-subject SPECT activation
      studies compared to normal data, as used in clinical applications. In principle,
      these findings can be extended to SPECT receptor studies or PET data.

PMID- 11969330
TI  - Image distortion correction in fMRI: A quantitative evaluation.
AB  - A well-recognized problem with the echo-planar imaging (EPI) technique most
      commonly used for functional magnetic resonance imaging (fMRI) studies is
      geometric distortion caused by magnetic field inhomogeneity. This makes it
      difficult to achieve an accurate registration between a functional activation map
      calculated from an EPI time series and an undistorted, high resolution anatomical
      image. A correction method based on mapping the spatial distribution of field
      inhomogeneities can be used to reduce these distortions. This approach is
      attractive in its simplicity but requires postprocessing to improve the
      robustness of the acquired field map and reduce any secondary artifacts.
      Furthermore, the distribution of the internal magnetic field throughout the head
      is position dependent resulting in an interaction between distortion and head
      motion. Therefore, a single field map may not be sufficient to correct for the
      distortions throughout a whole fMRI time series. In this paper we present a
      quantitative evaluation of image distortion correction for fMRI at 2T. We assess
      (i) methods for the acquisition and calculation of field maps, (ii) the effect of
      image distortion correction on the coregistration between anatomical and
      functional images, and (iii) the interaction between distortion and head motion,
      assessing the feasibility of using field maps to reduce this effect. We propose
      that field maps with acceptable noise levels can be generated easily using a dual
      echo-time EPI sequence and demonstrate the importance of distortion correction
      for anatomical coregistration, even for small distortions. Using a dual echo-time
      series to generate a unique field map at each time point, we characterize the
      interaction between head motion and geometric distortion. However, we suggest
      that the variance between successively measured field maps introduces additional
      unwanted variance in the voxel time-series and is therefore not adequate to
      correct for time-varying distortions.

PMID- 11969331
TI  - An investigation of functional and anatomical connectivity using magnetic
      resonance imaging.
AB  - This article examines functional and anatomical connectivity in healthy human
      subjects measured with magnetic resonance imaging methods. Anatomical
      connectivity in white matter is obtained from measurements of the diffusion
      tensor. A Monte-Carlo simulation determines the probability that a particle
      diffuses between two points, with the probability of a jump in a particular
      direction from a given voxel being based on the local value of the diffusion
      tensor components. Functional connectivity between grey matter pixels is assessed
      without recourse to a specific activation paradigm, by calculating the
      correlation coefficient between random fluctuations in the blood oxygenation
      level-dependent signal time course in different pixels. The methods are used to
      examine the anatomical and functional connectivities between crowns of adjacent
      gyri. A high functional connectivity was found between grey matter pixels, with
      white matter displaying only very low correlation. A comparison of the
      measurements of anatomical and functional connectivity found that there is no
      simple correlation between these measures, except that low values of functional
      connectivity were not found together with high values of anatomical connectivity.
      Furthermore pairs of regions situated around the central sulcus indicated a
      dependence of the two connectivity measures on each other. These results are in
      accordance with an interpretation that regions which are clearly directly linked
      by white matter fiber tracts should show high functional connectivity, but that
      the inverse need not be true as functional connectivity may also be indirectly
      mediated via more distant grey matter regions.

PMID- 11969332
TI  - Altered processing of acoustic stimuli during sleep: reduced auditory activation
      and visual deactivation detected by a combined fMRI/EEG study.
AB  - Although there is evidence that acoustic stimuli are processed differently during
      sleep and wakefulness, little is known about the underlying neuronal mechanisms.
      In the present study, the processing of an acoustic stimulus was investigated
      during different non rapid eye movement (NREM) sleep stages using a combined
      EEG/fMRI approach in healthy human volunteers: A text stimulus was presented to
      sleep-deprived subjects prior to and after the onset of sleep, and single-slice
      silent fMRI were acquired. We found significantly different blood oxygenation
      level-dependent (BOLD) contrast responses during sleep compared to wakefulness.
      During NREM sleep stages 1 and 2 and during slow wave sleep (SWS) we observed
      reduced activation in the auditory cortex and a pronounced negative signal in the
      visual cortex and precuneus. Acoustic stimulation during sleep was accompanied by
      an increase in EEG frequency components in the low delta frequency range.
      Provided that neurovascular coupling is not altered during sleep, the negative
      transmodal BOLD response which is most pronounced during NREM sleep stages 1 and
      2 reflects a deactivation predominantly in the visual cortex suggesting that this
      decrease in neuronal activity protects the brain from the arousing effects of
      external stimulation during sleep not only in the primary targeted sensory cortex
      but also in other brain regions.

PMID- 11969333
TI  - Frequency of concrete words modulates prefrontal activation during semantic
      judgments.
AB  - The effect of word frequency on semantic processing was characterized by studying
      two groups of right-handed participants using fMRI. Stimuli were presented in
      blocks of either high frequency or low frequency word triplets where a sample
      word appeared above a pair of test words. One group (n = 8) made semantic
      judgments by selecting the word from the test pair that was more closely
      associated with the sample. Stimulus triplets were designed such that relatedness
      between sample and "correct" items was obvious. The other group (n = 8) read the
      words silently without making any semantic decision and pressed a button on
      completing the reading of each triplet. Semantic judgments while no less
      accurate, were associated with greater left prefrontal BOLD signal change when
      they involved low frequency words, whereas there was no reliable effect of word
      frequency in the reading condition. These findings suggest that retrieval effort
      modulates left prefrontal activity when deliberate access to semantics is
      required.

PMID- 11969334
TI  - Analysis and design of perfusion-based event-related fMRI experiments.
AB  - Perfusion-based functional magnetic resonance imaging (fMRI) using arterial spin
      labeling (ASL) methods has the potential to provide better localization of the
      functional signal to the sites of neural activity compared to blood oxygenation
      level-dependent (BOLD) contrast fMRI. At present, experiments using ASL have been
      limited to simple block and periodic single-trial designs. We present here an
      adaptation of the general linear model to perfusion-based fMRI that enables the
      design and analysis of more complicated designs, such as random and semirandom
      event-related designs. Formulas for the least-squares estimate of the perfusion
      response and the F statistic for the detection of a response are derived. Exact
      expressions and useful approximations for detection power and estimation
      efficiency are presented, and it is shown that the trade-off between power and
      efficiency for perfusion experiments is similar to that previously observed for
      BOLD experiments. The least-squares estimate is compared with an estimate formed
      from the running subtraction of tag and control images. The running subtraction
      estimate is shown to be approximately equal to a temporally low-pass-filtered
      version of the least-squares estimate. Numerical simulations and results from ASL
      experiments are used to support the theoretical findings.

PMID- 11969335
TI  - Cytokines of the placenta and extra-placental membranes: biosynthesis, secretion
      and roles in establishment of pregnancy in women.
AB  - Virtually all known cytokines have been demonstrated to be expressed in the
      placenta and associated fetal and maternal membranes during normal gestation. In
      addition to playing their traditional roles as modulators of immunological
      function, cytokines derived from the placenta and extraplacental membranes,
      together with other locally-derived growth factors, appear to be implicated in
      various aspects of implantation and placental development. Imbalances in the
      intrauterine cytokine milieu around the time of implantation and invasion may
      play a causative role in disorders associated with early pregnancy failure, and
      are also associated with the abnormal trophoblast development seen in gestational
      trophoblastic disease. Cytokines thus appear to be an important component of a
      paracrine/autocrine communication network operating within the feto-maternal
      interface to ensure the successful establishment of pregnancy.

PMID- 11969336
TI  - Cytokines of the placenta and extra-placental membranes: roles and regulation
      during human pregnancy and parturition.
AB  - Summary In an earlier, companion, review, we concluded that cytokines produced by
      the placenta and associated membranes are likely to be involved in control of the
      processes of implantation and placental development (Bowen et al., 2002). In this
      review, we discuss evidence that cytokines continue to be part of a
      paracrine/autocrine regulatory network in the placenta and membranes throughout
      the mid and late stages of gestation. Cytokines are involved in regulation of
      placental growth during these later stages of pregnancy and also function to
      protect the fetus from pathological organisms. The evidence, while not entirely
      consistent, suggests that production of certain cytokines within the
      extraplacental membranes is altered during normal term parturition, whereas in
      the villous placenta evidence of labour-associated changes is much more
      equivocal. Roles for cytokines have been postulated in many facets of
      parturition, including expulsion of the fetus by uterine contractions, membrane
      rupture, and dilation of the cervix. Imbalances and disruptions to the cytokine
      milieu have been implicated in a number of diseases of pregnancy involving
      abnormalities of both placental growth/establishment and initiation of
      parturition. Cytokine secretion induced by intrauterine infection is associated
      with increased occurrence or severity of some neonatal diseases. This wealth of
      data supports the view that cytokines are an integral part of a functional
      regulatory/communication network operating within the placental-maternal unit
      during normal gestation.

PMID- 11969337
TI  - The tumour suppressor gene maspin is differentially regulated in cytotrophoblasts
      during human placental development.
AB  - Identification of factors that play a role in regulating the highly invasive
      ability of human placental cells throughout gestation will contribute to a better
      understanding of this unique developmental process. The aims of this study were
      to determine whether the tumour suppressor gene maspin is present in the human
      placenta and plays a putative role in the regulation of cytotrophoblast invasion
      during placental development. The data showed that the expression of maspin mRNA
      was maximum in term placentae compared to the first and second trimester tissues,
      and absent in the HTR-SVneo (immortalized extravillous cytotrophoblast), JEG-3
      and JAR (choriocarcinoma) cell lines. Maspin protein, detected by Western blot
      analysis, was twofold higher in the second trimester and 4.4-fold higher in the
      third trimester compared to the first trimester. Maspin immunohistochemical
      staining was localized in cytotrophoblasts with increased and more diffuse
      staining in the second and third trimesters. Corresponding to the period of
      maximum maspin expression, cytotrophoblasts isolated from term placentae had
      significantly lower invasive ability as compared to first and second trimester
      cytotrophoblasts (P< 0.03). Further, addition of recombinant maspin significantly
      decreased cytotrophoblast invasion in vitro by 40-50 per cent in all three
      trimesters of gestation. This study provides the first evidence of the temporal
      expression of maspin during human gestation and suggests a putative role for
      maspin in regulating the invasive activity of cytotrophoblasts at term. The down
      regulation of maspin expression may be critical at the time of implantation and
      early placental development, whereas upregulation of maspin may serve as a signal
      for the end of cytotrophoblast invasion and gestation.

PMID- 11969338
TI  - Characterization of the expression of the retinoid-related, testis-associated
      receptor (RTR) in trophoblasts.
AB  - Previous studies have provided evidence indicating that the nuclear orphan
      receptor RTR plays an important role during embryonic development and in
      spermatogenesis. In this study, we examine the expression of RTR in murine
      placenta and several human placental choriocarcinoma cell lines. Northern blot
      analysis showed high expression of RTR mRNA in placental tissue. In contrast to
      murine testis, which contains 7.4 and 2.3 kb transcripts, placental tissue
      expressed only the larger transcript. Examination of RTR expression in murine
      placental tissue by immunohistochemistry demonstrated the presence of RTR protein
      in the nuclei of giant trophoblasts and spongiotrophoblasts. RTR mRNA was also
      expressed in rat choriocarcinoma Rcho-1 cells and in the human placental
      choriocarcinoma cell lines BeWo, JAR, and JEG-3. In trophoblasts, RTR was co
      expressed with the estrogen-related receptors ERR alpha and ERR beta. Giant
      trophoblast differentiation in Rcho-1 cells, characterized by induction of
      placental lactogen I (PL-I), was accompanied by a steady decrease in the
      expression of RTR mRNA and down-regulation of ERR beta expression while levels of
      ERR alpha mRNA did not change significantly. RTR was able to inhibit ERR alpha
      mediated transactivation through the consensus RTR-response element (RTRE) likely
      by competing with ERR alpha for binding to the RTRE. These results suggest the
      possibility of cross-talk between RTR and ERR alpha receptor signalling pathways
      in trophoblasts.

PMID- 11969339
TI  - Localization of nuclear factor-kappa B (NF kappa B) and inhibitory factor-kappa B
      (I kappa B) in human fetal membranes and decidua at term and preterm delivery.
AB  - The human fetal membranes and decidua are thought to be involved in the onset of
      human parturition. These tissues produce and respond to various cytokines, which
      may be involved in preterm labour and possibly term labour. They also show
      increasing production of prostaglandins (PGs) with advancing gestation and
      labour. The expression of PGHS-2, a rate limiting enzyme in PG synthesis, is
      increased in the fetal membranes at labour. The gene for PGHS-2 and many of the
      cytokine genes (e.g. TNFalpha, IL-1, IL-6) are stimulated by the transcription
      factor NF kappa B. This factor is composed of two subunits, p50 and p65, which
      are localized in the cytoplasm bound to I kappa B. When activated I kappa B is
      metabolized, and p50, p65 translocate to the nucleus to activate various genes.
      The purpose of the present study was to examine the tissue and cellular
      distribution of p65 and I kappa B in the human fetal membranes and decidua
      throughout gestation. Term tissues were obtained prior to labour by elective
      caesarean section (n=10) or following vaginal delivery (n=10) and 10 preterm
      tissues were obtained following labour prior to 37 weeks gestation. None of the
      tissues had any evidence of infection. The immunoreactive NF kappa B and I kappa
      B were localized in the tissues. p65 protein was found in the nucleus and
      cytoplasm of cells in the amnion, chorion laeve and decidua. In the amnion and
      chorion laeve, no changes occurred in subcellular localization with advancing
      gestation or term labour. However, in the decidua, there was a marked increase in
      the nuclear localization of i.r. p 65 in tissues obtained at term when compared
      with tissues delivered preterm. In the case of I kappa B, it was localized to the
      cytoplasm of cells in all tissues and there was an increase i.r. I kappa B in
      decidua at term compared to preterm but no change occurred in the amnion or
      chorion. The increase in nuclear localization of p65 in the decidua that occurs
      with advancing gestation, highlights the potential importance of this factor in
      the regulation of parturition related genes in this tissue.

PMID- 11969340
TI  - The distribution of activin and activin receptors in gestational tissues across
      human pregnancy and during labour.
AB  - The aim of this study was to investigate localization and content of activin beta
      A-subunit and activin receptors in gestational tissues throughout pregnancy and
      in association with term labour. Placenta and fetal membranes were collected from
      women undergoing first and second trimester terminations and from women before
      and after term labour. Activin beta A-subunit and activin receptors IA, IB, IIA
      and IIB were studied by immunohistochemistry. Term tissues were analysed for
      activin A and follistatin content by ELISA and the presence of receptor proteins
      was assessed by Western hybridization. Activin beta A-subunit was localized to
      the syncytiotrophoblast and cytotrophoblast in placentae from all gestational
      ages, and to the amniotic epithelial and chorionic trophoblast layer at term. In
      placentae of first and second trimester, receptor proteins were localized to the
      syncytium, whereas at term, the distribution was confined predominantly to
      vascular endothelial cells of villous blood vessels. Receptor proteins in amnion
      were localized to some epithelial cells, mesenchyme and chorionic trophoblast.
      These findings suggest that activin A is secreted by and targets the placental
      syncytium and amniotic epithelium in early pregnancy, but at term targets the
      vascular endothelium of placenta and the fetal membranes. There were no
      differences with labour onset.

PMID- 11969341
TI  - The regional expression of insulin-like growth factor II (IGF-II) and insulin
      like growth factor binding protein-1 (IGFBP-1) in the placentae of women with pre
      eclampsia.
AB  - Insulin-like growth factors and their binding proteins regulate cellular
      proliferation, differentiation and function, and play an important role in
      placental development. IGF-II and IGFBP-1 are abundantly expressed by cells at
      the maternal-fetal interface and mediate cell-to-cell communication between
      trophoblasts and decidua. Placentae of pre-eclamptic pregnancies show villous
      cytotrophoblast proliferation, increased syncytial sprout formation and impaired
      trophoblast invasion. We hypothesized that the expression of IGF-II and IGFBP-1
      by cells at the maternal-fetal interface is altered in pre-eclampsia. We
      determined the regional abundance and cellular localization of IGF-II mRNA and
      IGFBP-1 mRNA and protein in placentae from normotensive control and pre-eclamptic
      pregnancies. IGF-II mRNA was expressed in both the chorionic villi and basal
      plate decidua regions. Increased IGF-II mRNA abundance was observed in the
      intermediate trophoblasts of peri-infarct regions. IGFBP-1 expression was present
      only in the decidua of the basal plate and membranes, and this expression was
      decreased significantly in pre-eclamptic placentae. The increased IGF-II
      expression in the intermediate trophoblast surrounding placental infarcts
      suggests a role for IGF-II in placental repair or remodelling. Decreased IGFBP-1
      mRNA expression in the basal plate decidua suggests that the increased
      concentrations of IGFBP-1 the circulation of pre-eclamptic women is not of
      decidual origin. The altered IGF-II and IGFBP-1 expression at the fetomaternal
      interface may be important in the pathophysiology of pre-eclampsia.

PMID- 11969342
TI  - TGF-beta 3 expression during umbilical cord development and its alteration in pre
      eclampsia.
AB  - Members of the TGF-beta family have been shown to play an important role in
      numerous tissues during development. In the present study we have investigated
      the spatial and temporal expression of TGF-beta 3, in human umbilical cord
      development. Total TGF-beta 3 protein content, assessed by immunoblotting,
      increased with advancing gestation as did immunostaining and mRNA in Wharton's
      jelly fibroblasts. Immunohistochemical analysis revealed that TGF-beta 3 was
      present in all cell types. Temporal changes in TGF-beta 3 expression were
      observed in the vascular smooth muscle cells, such that with advancing gestation
      TGF-beta 3 protein expression and became mostly restricted to the extracellular
      compartment of the vascular media. This was associated with a decrease in TGF
      beta 3 mRNA expression in umbilical vascular smooth muscle cells. Of clinical
      significance, umbilical cords from pregnancies complicated by pre-eclampsia,
      showed a significant reduction in total TGF-beta 3 protein expression when
      compared to those of age-matched patients. Both TGF-beta 3 mRNA and protein
      expression were downregulated in the endothelium and smooth muscle layers of the
      umbilical arteries, as well as in the Wharton jelly fibroblasts. Our data
      demonstrate that during umbilical cord development TGF-beta 3 expression is
      spatially and temporally regulated and that TGF-beta 3 expression is altered in
      umbilical cords of pregnancies complicated by pre-eclampsia. We speculate that
      the downregulation of TGF-beta 3 expression found in pre-eclamptic umbilical cord
      may contribute to the abnormal structure and mechanical properties seen in these
      pathological umbilical cords.

PMID- 11969343
TI  - Growth factor rescue of cytokine mediated trophoblast apoptosis.
AB  - INTRODUCTION: Apoptosis can be induced in cytotrophoblasts and
      syncytiotrophoblast in culture by a combination of TNF-alpha and IFN-gamma (Yui
      et al., 1994a; Garcia-Lloret et al., 1996). This apoptotic action of TNF-alpha
      and IFN-gamma can be inhibited/'rescued' by EGF (Garcia-Lloret et al., 1996).
      Additional 'survival' factors have been sought which might protect cells against
      apoptosis induced by TNF-alpha/IFN-gamma. The survival factors investigated were
      bFGF, IGF-1, PDGF-AA, VEGF and PLGF. These cytokines were chosen specifically
      because in common with EGF, the receptors for these molecules are all direct
      protein tyrosine kinases. MATERIALS AND METHODS: All the experiments were carried
      out using a standard cell culture protocol (Yui et al., 1994a, b; Garcia-Lloret
      et al., 1996). Apoptosis was induced using TNF-alpha/IFN-gamma, and rescue was
      attempted using the various cytokines. Apoptosis was identified using the TUNEL
      technique and quantified by counting 3000 cells in each experimental well.
      RESULTS: As in previous studies EGF produced a complete inhibition of the
      apoptotic action of TNF-alpha/IFN-gamma. bFGF, IGF-1, and PDGF-AA produced a
      partial but significant inhibition of the apoptotic action of TNF-alpha/IFN
      gamma. VEGF and PLGF in these experiments had no protective effects against TNF
      alpha/IFN-gamma induced apoptosis. DISCUSSION: Previous studies relating to EGF
      have been confirmed. bFGF, IGF-1, and PDGF have all been shown to provide partial
      protection against TNF-alpha/IFN-gamma induced apoptosis. VEGF and PLGF did not
      protect against apoptosis, and the mechanisms of action remain unclear.

PMID- 11969344
TI  - Placental apoptosis in discordant twins.
AB  - OBJECTIVE: To investigate placental apoptosis in discordant dichorial twins.
      METHODS: Placental samples were obtained from 7 third-trimester suitable twins.
      Discordancy was defined as a >25 per cent difference in newborn birth weight.
      Light microscopy using hematoxylin and eosin (H&E)-stained paraffin slides and
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labelling (TUNEL) methods were used to confirm the incidence of apoptosis.
      Investigators were blinded to pregnancy outcome. RESULTS: Both methods revealed
      that the incidence of apoptosis in the placentas of the smaller fetuses was
      significantly higher than in placentas of the larger fetuses. The incidence of
      TUNEL-positive cells in the former was 1.4+/-0.26 per cent: this was
      significantly higher than the incidence of apoptosis in the placental specimens
      of the latter (0.9+/-0.07 per cent, P< 0.02 Wilcoxon rank test). The same results
      were obtained with H&E: the incidence of apoptosis detected in placentas from the
      former was 1.07+/-0.1 per cent compared to 0.72+/-0.08 per cent in those of the
      latter (P< 0.02 Wilcoxon rank test). CONCLUSIONS: Despite similar environment
      conditions, placental apoptosis is increased in the smaller fetus and thus might
      play a role in discordancy between twins. Since increased placental apoptosis has
      also been found in singleton intrauterine growth restriction, this supports the
      hypothesis that the smaller twin is selectively growth restricted.

PMID- 11969345
TI  - Placental pathology in early onset pre-eclampsia and intra-uterine growth
      restriction in women with and without thrombophilia.
AB  - OBJECTIVE: The incidence of placental thrombotic lesions in early onset
      preeclampsia (PE) and/or intrauterine growth restriction (IUGR) were compared
      between women with and without thrombophilia or hyperhomocysteinemia. STUDY
      DESIGN: Matched case-control study. 183 women with a history of early onset PE
      and/or IUGR were tested for thrombophilia and hyperhomocysteinemia. From the 66
      women with a thrombophilic factor the placental histological slides were
      available in 47 women. These were matched for maternal condition (PE and/or
      IUGR), gestational age at delivery, parity and maternal age, to 47 women with no
      thrombophilic factor. All slides were revised for lymphohistiocytic villitis,
      fetal thrombosis and fibrin depositions. RESULTS: There were no significant
      differences between the placentas of the matched groups with and without a
      thrombophilic factor. CONCLUSION: Placental thrombotic and inflammatory lesions
      associated with early onset PE and/or IUGR do not occur more often in women with
      compared to women without thrombophilia or hyperhomocysteinemia.

PMID- 11969346
TI  - The epidemiology of placental infarction at term.
AB  - The incidence and associations of placental infarction at term were investigated
      as part of a population based case-control study of small for gestational age
      (SGA) infants. 509 placentas from women delivering SGA infants (SGAP) and 529
      placentas from women delivering infants with birthweights appropriate for
      gestational age (AGAP) were examined using fixed protocols for macroscopic
      identification and microscopic confirmation of infarction. Other information was
      obtained by maternal interview and from an obstetric database. Infarcts were
      found in 17.3 per cent of SGAP and 11.7 per cent of AGAP. This difference was in
      placentas with multiple infarcts not involving the placental margin and was
      significant in multivariate analysis (OR 1.66; 95 per cent CI 1.12,2.47).
      Multivariate analysis showed significant associations between the presence of any
      infarct and maternal hypertension in both SGAP (OR=4.00; 95 per cent CI
      1.96,8.16) and AGAP (OR 2.99; 95 per cent CI 1.23,7.32); maternal smoking,
      associated with a lesser risk in SGAP only (OR=0.31; 95 per cent CI 0.13,0.73);
      maternal age at first pregnancy in a linear relationship with AGAP only (beta co
      efficient 0.09, P=0.0034); and between some ethnic groups. We conclude that at
      least five factors have independent associations with the incidence of placental
      infarction and these associations differ by site and age of infarcts.

PMID- 11969347
TI  - Microsomal acetoxy drug: protein transacetylase of placenta: part 1.
      Characterization of DAMC: GST transacetylase.
AB  - We have earlier established in tissues of several mammalian animal species the
      existence of a novel membrane bound enzyme termed 7,8-diacetoxy-4-methylcoumarin
      (DAMC): protein transacetylase (TAase) that possibly transfers acetyl groups from
      the model acetoxy drug (DAMC) to certain enzyme protein viz. glutathione S
      transferase (GST), cytochrome P-450 and NADPH cytochrome C reductase leading to
      the drastic modulation of their catalytic activities. We have in this report
      extended the studies to human tissue and characterized TAase from placenta. For
      this purpose placental microsomes were preincubated with DAMC along with the
      receptor protein (cytosolic GST) followed by the addition of the substrates of
      GST in order to quantify the catalytic activity of GST, the extent of inhibition
      of GST served as a measure of TAase. Placental TAase was also found to
      irreversibly activate NADPH cytochrome C reductase by DAMC. Placental enzyme
      activated the reductase even at very low concentration of DAMC. Iodoacetamide
      nearly abolished the placental TAase suggesting the presence of active thiol
      group in the enzyme and the TAase demonstrated hyperbolic kinetics. Kinetic
      constants obtained by varying the concentrations of either of the substrates DAMC
      or cytosolic GST characterized TAase catalysed reaction as the bimolecular
      reaction. Further studies are in progress to delineate the physiological
      importance of TAase in placenta.

PMID- 11969349
TI  - Page for patients. Urinary incontinence.

PMID- 11969348
TI  - Energy from fat is associated with obesity in U.S. men: results from the Prostate
      Cancer Prevention Trial.
AB  - BACKGROUND: Diets high in fat have been proposed as one cause of obesity,
      primarily because fat is more energy-dense than other macronutrients. However,
      the literature on fat consumption and human obesity is inconclusive. This
      research examines associations between dietary fat intake and obesity in men
      participating in the Prostate Cancer Prevention Trial. METHODS: Data in this
      cross-sectional study are from 15,266 men (55-79 years) who completed
      questionnaires on usual diet, physical activity, and health-related
      characteristics. Height and weight were collected by clinic personnel. Obesity
      was defined as body mass index (BMI) greater than or equal to 30 kg/m2. RESULTS:
      In this healthy cohort, 23.3% were obese. Younger age, a sedentary lifestyle,
      lower education, and black race were positively associated with obesity (all P <
      0.001). Using two statistical approaches, both total energy and energy from fat,
      but not total energy from other macronutrients, increased linearly and
      significantly with increasing BMI. Mean fat intake increased from 691 kcal (31.4%
      energy) among normal-BMI men to 797 kcal (34.3% energy) among the obese (P for
      trend <0.001). After controlling for demographic and health-related
      characteristics in regression models, BMI increased by 0.53 and 0.14 kg/m(2) for
      every 500 kcal of fat and total energy consumed, respectively. Energy
      underreporting, based on estimated basal metabolic rate and physical activity,
      was fourfold higher among obese compared to normal-weight men. CONCLUSIONS: In
      this large cohort of healthy older men, energy from fat was associated with
      obesity, suggesting that high-fat dietary patterns are contributing to the high
      rates of obesity in U.S. men.

PMID- 11969350
TI  - Preconception care: a screening tool for health assessment and risk detection.
AB  - BACKGROUND: Identification of risk factors for adverse pregnancy outcome is a
      main component of preconception care, but requires adequate time and knowledge.
      This study compares self-administered questionnaires to history taking by a
      physician to evaluate the reliability of such a screening tool for prepregnancy
      risk detection. METHODS: One hundred ninety-three women from the outpatient
      clinic of Obstetrics and Gynecology of the University Medical Center Nijmegen,
      The Netherlands, were included in a study on preconception care. A
      Preconceptional Health Assessment form with risk variables pertaining to social,
      nutritional, medical, infectious disease, medication, reproductive and family
      history, and two Family History surveys (for the woman and her partner) were
      completed by 186 couples at home. A physician then orally verified the written
      answers. Agreement between the written and the oral answers was calculated using
      kappa statistic. RESULTS: An excellent agreement level was found for all sections
      of the Preconceptional Health Assessment form (overall kappa = 0.88) except for
      nutritional history (kappa = 0.70). The Family History surveys also showed a high
      agreement level (kappa = 0.92 for women and kappa = 0.90 for men). CONCLUSIONS:
      The questionnaires are an accurate screening tool for preconceptional risk
      factors. We advocate their implementation in various settings to facilitate the
      provision of preconception care.

PMID- 11969351
TI  - Sexual behavior of drug-users: is it different?
AB  - BACKGROUND: Across the world, drug-users (DU) have been shown to be at greater
      risk of contracting and transmitting sexually transmitted diseases and HIV
      infection. However, in the metropolitan cities of India, where drug-use patterns
      may uniquely vary between injection and noninjection, depending on drug
      availability, little is known about the risk behavior of drug-users. OBJECTIVE:
      The objective of the study was to find out whether drug-users are more likely to
      practice high-risk sexual behavior compared to non-drug users. METHODS: The
      sexual behavior of 70 drug-users, selected by snowball sampling, was compared
      with 128 age- and economic status-matched controls (non-drug-users), randomly
      selected from the same community. RESULTS: Seventy-eight percent sexually active
      drug-users and 43% sexually active non-drug-users had multiple sex partners (P <
      0.02). The average number of sex partners was significantly higher among the drug
      users (P = 0.05). Anal intercourse was practiced by 25.7% drug-users and 8.6% non
      drug-users (OR = 3.7; P < 0.01). The drug-users were 6.7 times more likely to
      visit commercial sex workers (P < 0.0001). Sexually transmitted disease
      prevalence was higher among the drug-users (P < 0.003). CONCLUSIONS:
      Notwithstanding the small sample size, this study shows that drug-users practice
      high-risk sexual behavior more frequently. Interventions, in the form of
      awareness generation and prevention education programs, are required in order to
      reduce risk of sexually transmitted diseases and HIV transmission among drug
      users.

PMID- 11969352
TI  - The incidence and context of tobacco use in popular movies from 1988 to 1997.
AB  - OBJECTIVE: The aim of this study was to describe tobacco use in a large
      representative sample of movies. METHODS: We analyzed the content of the top 25
      box office hits per year from 1988 to 1997. Outcomes included the number of
      occurrences of tobacco use, the time tobacco use appeared on screen, the context
      in which tobacco use was portrayed, and characteristics of smokers compared with
      nonsmokers. RESULTS: Eighty-seven percent of the movies portrayed tobacco use,
      with a median of 5 occurrences per film. Tobacco use was not related to year of
      release or box office success of the movie. R-rated movies had the greatest
      number of occurrences (median = 8.5; P < 0.05) and were most likely to feature
      major characters using tobacco (81%, P < 0.001). Among major characters, males
      were more likely to use tobacco than females (28% vs 17%, P < 0.001), but there
      was no difference in the prevalence of tobacco use by age, race, or socioeconomic
      status. Tobacco users were typically adults (96.3%) who were more likely to
      engage in a variety of other risk behaviors. Most tobacco use involved cigarettes
      or cigars (89.5%). Motivations for on-screen smoking included agitation (20.1%),
      sadness (5.1%), happiness (15.3%), and relaxation (17.1%). Characters were often
      shown smoking while confiding in others (30.7%) or in social/celebratory
      situations (18.0%). Negative reactions to tobacco use were rarely shown (5.9%)
      and negative consequences resulting from tobacco use were depicted for only 3.4%
      of the major characters who used tobacco. CONCLUSION: Despite increasing anti
      smoking sentiments in our society, negative reactions to smoking are rare and
      there is no evidence that tobacco use in movies has declined over the past
      decade. Movies continue to model smoking as a socially acceptable behavior and
      portray it as both a way to relieve tension and something to do while
      socializing. By depicting positive images of tobacco use, movies have the
      potential to influence adolescent smoking behavior as much as any other
      environmental exposure, such as family or friend smoking.

PMID- 11969353
TI  - Pregnant African-American teens are less likely than their nonpregnant peers to
      use condoms.
AB  - OBJECTIVE: The aim of this study was to prospectively compare pregnant and
      nonpregnant adolescents' recent condom use and sexually transmitted disease (STD)
      acquisition. METHODS: Sexually active African-American females (N = 522), ages 14
      18, were recruited from clinics and schools. Adolescents completed baseline
      interviews and provided vaginal swabs for STD testing, and urine for pregnancy
      testing. Assessments were repeated 6 and 12 months post baseline assessment.
      Analyses compared adolescents who became pregnant between baseline and the 6
      month assessment with their peers who had negative pregnancy tests. Condom use
      between the 6- and 12-month assessments and incidence of STDs at the 12-month
      assessment served as outcomes. Adolescents who did not report sexual activity
      between the 6- and 12-month assessments were excluded. RESULTS: Ten percent of
      the adolescents became pregnant and continued sexual activity. Pregnant
      adolescents reported less overall condom use (P < 0.0001), more infrequent condom
      use (adjusted odds ratio [AOR] = 4.5, P < 0.001), and more unprotected vaginal
      sex (AOR = 4.7, P < 0.003). Pregnant adolescents were equally likely to test
      positive for STDs (31% vs 26%) and to self-report having STDs at the 12-month
      follow-up period (30% vs 23%). CONCLUSIONS: Findings suggest that pregnant
      adolescents may be less likely to use condoms than their nonpregnant peers and
      that STD incidence among pregnant adolescents may be high. Condom use promotion
      may be important during adolescents' prenatal care.

PMID- 11969354
TI  - Female patients tend to alter their diet following the diagnosis of rheumatoid
      arthritis and breast cancer.
AB  - BACKGROUND: Breast cancer and rheumatoid arthritis are common diseases which
      change everyday life among women. This study investigated the beliefs and
      attitudes of female patients regarding diet and their need for dietary counseling
      in relation to years since diagnosis, age, and education. METHODS: Breast cancer
      (BC) patients were compared to patients with rheumatoid arthritis (RA) with a
      validated questionnaire. Logistic regression models were used to adjust for the
      differences in demographic patient characteristics between BC and RA. In
      addition, the influence of demographic variables was studied further in the BC
      and RA groups, separately or combined. chi(2) testing was used to analyze the
      associations between demographic and dietary variables. RESULTS: Eight percent of
      BC patients and 40% of RA patients considered diet a factor contributing to their
      disease (P < 0.0001). Thirty percent of BC patients and 51% of those with RA
      reported having changed their diet after their diagnosis (P = 0.0003, chi(2)).
      The patients with RA had a 3.9 times higher assumption on the diet and disease
      connection compared to breast cancer patients (OR = 3.92, P = 0.002). Longer (>5
      years) time to diagnosis increased the probability 2.6 times. The main reason for
      the change in diet was the desire for cure. The main changes reported included
      reduced consumption of animal fat, sugar, and red meat and increased consumption
      of fruit and vegetables. The source of information was most commonly the mass
      media and a need for more information on dietary factors relating to disease was
      expressed. CONCLUSIONS: We observed the patients to express an interest in
      alternative dietary habits, with the focus on a healthier diet. The lack of
      precise dietary recommendations for individual disease situations was expressed
      strongly and patients depended on information from outside their treatment
      center.

PMID- 11969355
TI  - An intervention study on screening for breast cancer among single African
      American women aged 65 and older.
AB  - BACKGROUND: Older African-American women with single marital status are least
      likely to use screening procedures. This study aimed to evaluate a breast
      screening intervention program conducted in this population. METHODS: Ten public
      housing complexes were randomly assigned to either the intervention or the
      control group. African-American women aged 65 and over were recruited into the
      study if they were widowed, divorced, separated, or never married and did not
      have a history of breast cancer (n = 325). The intervention program was delivered
      by lay health educators at the participant's apartment and was designed to
      increase knowledge about breast screening, reduce psychological problems, and
      increase support from significant others. Breast-screening-related cognition and
      behavior were measured at baseline and at 1 and 2 years postintervention.
      RESULTS: Comparisons of the preintervention and postintervention measurements
      showed that while the proportion of women who had a clinical breast examination
      or mammogram in the preceding year was decreased at 1 year postintervention in
      the control group, it was increased in the intervention group. However, the
      differences did not reach a significant level. No consistent patterns could be
      found in changes of breast self-examination and variables in knowledge,
      attitudes, and beliefs. When analyses were restricted to women whose significant
      others had provided information or help on breast screening, results were better,
      but the differences between the intervention and control groups still did not
      reach statistical significance. CONCLUSIONS: These results did not suggest
      significant effects of an intervention program that used lay health educators to
      promote breast cancer screening in older single African-American women.

PMID- 11969356
TI  - Application of a falls prevention program for older people to primary health care
      practice.
AB  - BACKGROUND: Our research group has established the effectiveness of an
      individually tailored home exercise program to prevent falls and fall injuries in
      older people in four controlled trials. In one of these trials we evaluated the
      applicability of the exercise program to routine primary health care practice and
      the feasibility of nurses implementing the program. METHODS: People aged 80 years
      and older, registered with general practices in three exercise (n = 330
      participants) and four control centers (n = 120 participants) in New Zealand,
      were invited to take part by their doctor. We investigated program reach, uptake,
      and compliance. We carried out physical assessments at baseline and after 1 year
      to assess the impact of the program. RESULTS: Most (85%) doctors agreed to take
      part and they approved 71% of patients to undertake the exercise program. Overall
      47% of people invited agreed to participate and 70% of the exercise participants
      remained exercising at 1 year. Balance score and chair stand time improved by a
      similar amount in each exercise center compared with the control centers.
      CONCLUSIONS: This falls prevention program is acceptable to older people and
      their doctors. Nurses trained by a physiotherapist can deliver the home exercise
      program effectively in routine primary health care practice.

PMID- 11969357
TI  - Provider-staff discrepancies in reported immunization knowledge and practices.
AB  - BACKGROUND: The purpose of the study was to compare immunization-relevant
      knowledge, certainty about knowledge, self-efficacy, vested interest, and
      reported practices of providers and clinical staff in the same clinics. METHODS:
      A valid and reliable instrument measuring the aforementioned issues was developed
      and administered to a sample of 50 providers and 60 members of the clinical
      staff. RESULTS: Providers were significantly more knowledgeable than staff (P <
      0.001); however, they were not more certain about their knowledge (P = 0.52) nor
      were they more confident in their capability to properly immunize all children in
      their practice (P = 0.10). Providers reported lower vested interest in
      immunizations than clinical staff (P < 0.05). Both groups were equally likely to
      immunize a child with a cold. Providers were less likely to defer needed
      immunizations for a 15-month-old child, and they were more likely to administer
      multiple injections to an 18-month-old (both P < 0.05). Providers were more
      likely than staff to immunize during acute and chronic illness visits (both P <
      0.001), and both groups were equally likely to immunize during preventive visits.
      CONCLUSIONS: Discrepancies in reported immunization practices between providers
      and staff may be a barrier to full immunization.

PMID- 11969358
TI  - Inhaled nitric oxide and methemoglobin in full-term infants with persistent
      pulmonary hypertension of the newborn.
AB  - Inhaled nitric oxide (iNO), a potent pulmonary vasodilator, has become a mainstay
      therapy for neonates with persistent pulmonary hypertension of the newborn
      (PPHN). However, it also oxidizes hemoglobin to methemoglobin (metHgb), thereby
      reducing the delivery of oxygen to tissues. Studies have suggested that elevated
      levels of metHgb may be avoided by limiting iNO concentration to less than 40
      parts per million (ppm). However, the relationship between iNO exposure and
      elevated levels of metHgb (greater than 4%) has not been examined. Therefore, we
      studied this relationship in full term newborns with PPHN. We reviewed the charts
      of twenty-eight neonates with a diagnosis of PPHN admitted to our Intensive Care
      Nursery between 1/92 and 10/97. Our retrospective analysis demonstrated that: (1)
      high metHgb levels can occur with exposure to low iNO concentration (three of
      eight newborns with maximum metHgb levels >4% had been exposed to no more than 40
      ppm of iNO concentration); and (2) cumulative iNO ( summation operatoriNO)
      exposure was the best predictor of elevated metHgb levels (seven of nine newborns
      receiving summation operatoriNO>2000 ppm x hour had maximum metHgb levels >4%).

PMID- 11969359
TI  - Modulation of TNF and GM-CSF release from dispersed human nasal polyp cells and
      human whole blood by inhibitors of different PDE isoenzymes and glucocorticoids.
AB  - The aim of this study was to investigate the role of the inhibitors of different
      PDE isoenzymes (PDE 1-5) on the production of two pro-inflammatory cytokines -
      tumor necrosis factor alpha (TNF) and granulocyte-macrophage colony-stimulating
      factor (GM-CSF). Two in vitro models were used to compare the antiinflammatory
      properties of PDE inhibitors with that of glucocorticoids. The effect on TNF
      release from diluted human blood following lipopolysaccharide (LPS from
      Salmonella abortus equi) stimulation as well as the GM-CSF and TNF release from
      human nasal polyp cells following allergic stimulation were investigated. Both
      models proofed to be well suited for the characterisation of the antiinflammatory
      properties of new chemical entities. In diluted human blood and dispersed human
      nasal polyp cells the induced TNF release was most potently suppressed by
      selective PDE4 inhibitors. Amrinone and milrinone, selective PDE3 inhibitors,
      suppressed TNF secretion to a lesser extent. The effects of theophylline
      (unspecific PDE inhibitor), vinpocetine (PDE1 inhibitor), EHNA (PDE2 inhibitor)
      and the PDE5 inhibitors zaprinast and E 4021 were weak. In human blood, the
      tested glucocorticoids beclomethasone, dexamethasone and fluticasone inhibited
      the LPS induced TNF release potently in a concentration dependent manner, whereas
      in dispersed human nasal polyp cells, the effect of the glucocorticoids on
      allergically induced TNF release, with the exception of dexamethasone, was much
      less pronounced. Glucocorticoids were the most potent inhibitors of GM-CSF
      release and the effect correlates well with the affinity to the glucocorticoid
      receptor. The selective PDE 4 inhibitors, and to a certain extent the PDE3
      inhibitors amrinone and milrinone, reduced the GM-CSF release in a concentration
      dependent manner. In all investigations selective PDE4 inhibitors reduced TNF
      release to a much higher degree (4-10 fold) than GM-CSF release.

PMID- 11969360
TI  - Cefuroxime vs a dicloxacillin/chloramphenicol combination for the treatment of
      parapneumonic pleural effusion and empyema in children.
AB  - The aim of this study was to evaluate the efficacy of cefuroxime, compared with
      the combination of dicloxacillin/chloramphenicol, for the treatment of children
      with parapneumonic pleural effusion or empyema. Forty patients, aged 3 months to
      5 years, with pleural effusion or empyema were randomized to receive cefuroxime
      (100 mg/kg/day) IV (n=20) or chloramphenicol (100 mg/kg/day) plus dicloxacillin
      (200 mg/kg/day) IV (n=20). Both groups were similar in age, days of illness,
      clinical and radiological findings, and etiology. Most patients (70%) had an
      empyema at presentation. There was no difference in clinical outcomes, including
      days to defervescence, duration of respiratory distress, duration of chest tube
      drainage, and days to discharge from hospital. The complication rates were
      similar in both groups. Pleural thickening occurred in four patients,
      bronchopleural fistula in two, and loculated empyema in one patient of each
      treatment group. Adverse effects attributed to cefuroxime were mild and
      infrequent. These results suggest that cefuroxime is an effective and well
      tolerated alternative for the treatment of children with pleural effusion and
      empyema.

PMID- 11969361
TI  - Leukotoxin-activated human pulmonary artery endothelial cell produces nitric
      oxide and superoxide anion.
AB  - To provide evidence that pulmonary endothelial cells exposed to 9,10-epoxy-12
      octadecenoate (Lx) produce nitric oxide (NO) and superoxide anion (O(2)(*-), we
      measured NO production, using a NO chemiluminescence analyzer, and nitric oxide
      synthase (NOS) activity, monitoring the conversion of L- [14C] arginine to L-
      [14C] citrulline, and O(2)(*-) by a fluorescence assay using a fluorescence
      spectrophotometer with hydroethidine (HE) in human pulmonary artery endothelial
      cells (HPAEC). NO production and eNOS were increased significantly when HPAEC
      were incubated with 10 microM Lx, and this effect was inhibited by L-NMMA or in
      the absence of extracellular Ca2+. Addition of 10 mM HE to the cell suspension
      spontaneously and continuously caused a subtle increase in fluorescence
      intensity, due to intracellular oxidation of HE to ethidium bromide (EB).
      Treatment of the cell suspension with Lx after the addition of HE exerted a dose
      dependent increase in intracellular EB fluorescence. Pre-treatment with
      allopurinol, a xanthine oxidase inhibitor, decreased the intracellular EB
      fluorescence by 54% in HPAEC incubated with 100 microM Lx. These results show
      that Lx induces NO production via activation of eNOS and O(2)(*-) production in
      endothelial cells via activation of cellular xanthine oxidase. Thus, Lx is a
      bioactive lipid.

PMID- 11969362
TI  - Review of the molecular and cellular mechanisms of action of glucocorticoids for
      use in asthma.
AB  - Asthma is characterized by inflammation in the lung and glucocorticoids (GCs) are
      the most clinically effective treatment available. The success of chronic GC
      therapy for asthma stems largely from the ability of the GC-GC receptor (GR)
      complex to alter transcription of a wide array of molecules involved in the
      inflammatory process. Many of the adverse effects of elevated systemic GC levels
      have been reduced through the use of inhalation as a method of administration, as
      opposed to oral GC. GCs exert their effects by binding to the wild-type GR,
      GR(alpha). The GR(alpha) complex can directly or indirectly alter gene
      transcription by binding to specific DNA sites or by activating transcription
      factors. There is also evidence to support GR(alpha) involvement in post
      translational activities. In the management of asthma, the GR(alpha) down
      regulates proinflammatory mediators such as interleukin-(IL)-1, 3, and 5, and up
      regulates anti-inflammatory mediators such as IkappaB [inhibitory molecule for
      nuclear factor kappaB1 IL-10, and 12. Newer GCs are being designed to increase
      potency and topical activity. Mometasone furoate (MF), has recently been
      developed for the treatment of asthma and inhibits key anti-inflammatory
      processes with a potency equal to or greater than that of fluticasone propionate.
      A better understanding of the molecular mechanisms involved might provide
      strategies for optimizing the effectiveness of GC in the treatment of asthma.

PMID- 11969363
TI  - Nerve growth factor and asthma.

PMID- 11969364
TI  - Gene therapy for inherited lung disorders: an insight into pulmonary defence.
AB  - This review summarizes the latest developments in viral and nonviral gene
      delivery systems to the lung, and the problems that have to be overcome. Gene
      delivery has the potential to offer effective treatment to patients with life
      threatening lung diseases such as cystic fibrosis and alpha(1)-antitrypsin
      deficiency, and could modify gene-environment relationships in asthma and other
      respiratory diseases. Phase I clinical trials conducted in the early 1990s showed
      that in principle gene transfer to the lung was safe. Although the preliminary
      results gave encouraging laboratory data, gene expression from viral or nonviral
      gene delivery systems was too inefficient or transient to offer clinical benefit.
      Initial optimism gave way to the realization that gene therapy to the lung was
      unlikely to be straightforward. The host innate and acquired immune system, which
      protects against infection from inhaled bacteria and viruses, represents a major
      barrier to successful gene transfer to the lung. A better understanding of the
      immunological barriers which exist in the lung may allow the development of
      pharmacological and/or immunological agents that modulate the host immune system
      to allow for a more continuous and regulated level of gene expression following
      gene transfer.

PMID- 11969366
TI  - EG-VEGF and the concept of tissue-specific angiogenic growth factors.
AB  - The endothelium of the vascular beds is extremely diverse and exquisitely
      distinct with respect to the specific tissue compartment served by the vessels.
      The molecular identity and function of the instructive signals that tailor the
      tissue-specific endothelial phenotype have been largely undefined. Presumably, a
      complex, integrated network of signals derived from the tissue parenchyma and/or
      stromal compartments is responsible. Recently, we identified a novel angiogenic
      mitogen, endocrine-gland-derived vascular endothelial growth factor, EG-VEGF,
      with a selective activity and very distinct expression pattern. Human EG-VEGF is
      expressed by steroid producing cells in the adrenal gland, placenta, testis and
      ovary, and is a mitogen for endothelial cells derived from these microvascular
      beds. EG-VEGF may represent the first of a novel class of tissue-specific
      angiogenic factors that function to regulate and fine-tune endothelial cell
      growth, structural and functional properties. The identification of other
      selective angiogenic molecules will allow insight into exciting, basic
      developmental issues and increase our armamentarium of factors for therapeutic
      angiogenic and anti-angiogenic strategies.

PMID- 11969367
TI  - Lymphatic endothelial regulation, lymphoedema, and lymph node metastasis.
AB  - Vascular endothelial growth factor receptor-3 (VEGFR-3) mediates lymphatic
      endothelial cell (LEC) growth, migration, and survival by binding VEGF-C and VEGF
      D. Recent studies have revealed new regulators of the lymphatic endothelium, such
      as the transcription factor Prox1, and the cell surface proteins podoplanin and
      lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). Furthermore, the
      isolation of LECs now allows detailed molecular studies of the factors regulating
      the lymphatic vasculature. These studies are aimed at targeting the lymphatic
      vasculature in the treatment of various diseases, such as tumour metastasis and
      lymphoedema.

PMID- 11969368
TI  - The angiopoietins and Tie2/Tek: adding to the complexity of cardiovascular
      development.
AB  - The expansion or remodelling of pre-existing blood vessels, known as
      angiogenesis, by either nascent sprouting, intercalated or intussusceptive growth
      is a highly regulated process. Angiogenesis is critical not only during normal
      embryonic vascular development, but also in the progression of several diseases,
      including cancer, psoriasis, and diabetes. Mouse molecular genetic experiments
      have shown that the angiopoietins and their receptor Tie2/Tek are indispensable
      for embryonic vessel development. The importance of the angiopoietin-signalling
      pathway has also been shown to extend beyond development, into in vitro and in
      vivo experimental models of angiogenic growth. Currently the precise role of the
      angiopoietins remains unclear. However, what is emerging from genetic, xenograft
      transplant, histochemical and cell culture experiments are that the response of
      endothelial cells to angiopoietins appears to be context and endothelial cell
      type specific.

PMID- 11969369
TI  - Oxygen sensors and angiogenesis.
AB  - Local oxygen tension has a profound effect on the vasculature, which compensates
      vascular insufficiency through the induction of angiogenesis. An important
      mediator in this process is the hypoxia-inducible factor (HIF) complex, which is
      activated in hypoxic cells and increases transcription of a broad range of genes
      including angiogenic growth factors such as VEGF. HIF is primarily regulated
      through oxygen-dependent proteasomal destruction of the regulatory subunit, HIF-1
      alpha or HIF-2 alpha. Regulation is through the modification of specific prolines
      in HIF- alpha chains which are hydroxylated by a recently identified family of
      enzymes which require molecular oxygen and 2-oxoglutarate as cosubstrates, and
      iron as a cofactor. Following modification HIF- alpha chains are captured by a
      ubiquitin ligase E3 complex containing the von Hippel-Lindau (VHL) tumour
      suppressor protein. The HIF prolyl hydroxylases (PHD enzymes) act as oxygen
      sensors regulating HIF, and hence angiogenesis. The PHD-HIF-VHL system provides a
      range of opportunities for therapeutic manipulation.

PMID- 11969370
TI  - Vascular and neuronal effects of VEGF in the nervous system: implications for
      neurological disorders.
AB  - Vascular endothelial growth factor (VEGF) was originally discovered as an
      endothelial-specific growth factor. While the predominant role of this growth
      factor in the formation of new blood vessels (angiogenesis) is unquestioned,
      recent observations indicate that VEGF also has direct effects on neurons and
      glial cells, and stimulates their growth, survival and axonal outgrowth. Because
      of these pleiotropic effects, VEGF has now been implicated in several
      neurological disorders both in the preterm infant (leukomalacia) and the adult
      (stroke, neurodegeneration, cerebral and spinal trauma, ischemic and diabetic
      neuropathy, nerve regeneration). A challenge for the future is to unravel to what
      extent the effect of VEGF in these disorders relates to its angiogenic activity
      or direct neurotrophic effect.

PMID- 11969371
TI  - Vascular patterning by Eph receptor tyrosine kinases and ephrins.
AB  - During vertebrate development, morphologically and functionally very different
      tissue types and organ systems need to be generated and organised in close
      coordination with each other. Blood vessels, which become critically required
      during early embryogenesis and remain indispensable throughout life, need to
      integrate into a great diversity of tissue types and adapt to both local and
      systemic requirements of the organism. Far from being randomly placed and
      uniformly shaped tubes, blood vessels form, with some degree of flexibility, a
      highly organised and precisely arranged network. Their differentiation,
      ultrastructure and physiology are well adapted to the requirements and functions
      of the surrounding tissues. How coordinated development and differentiation are
      achieved at a molecular level remains to be characterised. This review highlights
      the large family of Eph receptor tyrosine kinases and their ligands, called
      ephrins, which, because of their versatile functions in many cell and tissue
      types and their molecular complexity, might well provide one example of a control
      system integrating blood vessel and tissue morphogenesis.

PMID- 11969372
TI  - Contribution of marrow-derived progenitors to vascular and cardiac regeneration.
AB  - Adult bone marrow is a rich reservoir of tissue-specific pluripotent stem and
      progenitor cells. Accumulating evidence suggest that these cells have the
      potential of contributing to tissue revascularization and cardiac regeneration.
      Physiological stress results in the release of specific chemokines and cytokines
      that promote mobilization of stem cells to the peripheral circulation.
      Incorporation of these mobilized cells contributes to formation of functional
      vasculature and sets up stage for tissue regeneration. Vascular Endothelial
      Growth Factor (VEGF) through interaction with its receptors VEGFR2 and VEGFR1
      expressed on endothelial and hematopoietic stem cells promote recruitment of
      these cells into the sites of tissue injury accelerating vascular healing.
      Similarly, subset of CD34 + marrow derived cells are mobilized and recruited to
      the ischemic myocardium, differentiating into cardiac and vascular cells,
      restoring cardiac function. Identification of cellular mediators and tissue
      specific chemocytokines that facilitate selective recruitment of marrow-derived
      stem and progenitor cells to specific organs, will open up new avenues to
      accelerate cardiovascular regeneration and tissue revascularization.

PMID- 11969373
TI  - Differential modulation of apoptosis and necrosis by antioxidants in
      immunosuppressed human lymphocytes.
AB  - In the present study, we explored whether mitogenic stimulation of dexamethasone
      (DXM)- and cyclosporine A (CsA)-immunosuppressed peripheral blood lymphocytes
      (PBML) induced apoptosis or necrosis and their relation with the production of
      reactive oxygen intermediates. Our results indicate that both phenomena can occur
      in these cells and that antioxidants such as N-acetyl cysteine (NAC) and ascorbic
      acid (AA) can modulate them. However, DXM-induced apoptosis was only partially
      inhibited by NAC and AA, suggesting that DXM-treated PBMC had an additional
      apoptotic pathway independent of ROIs. Furthermore, we observed that the
      inhibition of apoptosis by antioxidants correlated with an increased cell
      proliferation, suggesting that the immunomodulation of both DXM and CsA may be
      related to induction of apoptosis. The ability to differentially modulate
      apoptosis and necrosis by antioxidants opens new possibilities in the management
      of immunosuppressive therapy, since the inhibition of necrosis may avoid
      inflammation and the tissue damage associated with immunosuppressors.

PMID- 11969374
TI  - Percutaneous penetration and metabolism of 2-ethoxyethanol.
AB  - Percutaneous absorption and cutaneous metabolism of 2-ethoxyethanol were assessed
      in vivo and with an in vitro flow-through diffusion system. Topical application
      of undiluted (14)C-ethoxyethanol to occluded rat skin in vivo resulted in 25% of
      the dose being absorbed after 24 h. The major routes of excretion included the
      urine (15%), expiration as carbon dioxide (6%), and feces (1.2%), while little of
      the dose remained in the carcass (1.3%). Free ethoxyethanol, ethoxyacetic acid,
      and glycine conjugate were detected in urine. Permeation rates of ethoxyethanol
      through unoccluded rat split skin (20%) were greater than rat whole skin (11%),
      while absorption through human split skin (8%) was lower than the rat. Absorption
      of undiluted ethoxyethanol through occluded rat split skin in vitro (22%) most
      accurately predicted absorption through rat skin in vivo. However, ethoxyethanol
      absorption (29%) was enhanced by application in methanol. First pass metabolism
      of ethoxyethanol was not detected during percutaneous penetration through viable
      human or rat skin in vitro or rat skin in vivo. However, rat skin cytosol had the
      potential to metabolize ethoxyethanol, suggesting that the rapid penetration
      through skin in vivo prevented metabolism and that systemic exposure after skin
      contact with 2-ethoxyethanol is likely to be to the parent compound. In
      conclusion, the in vitro system provided a reasonable estimate of dermal
      absorption for the rat in vivo and comparison of human and rat skin in vitro
      indicated 2-ethoxyethanol absorption in humans is about one-third of that in the
      rat.

PMID- 11969375
TI  - Arsenite disrupts mitosis and induces apoptosis in SV40-transformed human skin
      fibroblasts.
AB  - Chronic ingestion of arsenite-contaminated drinking water causes skin, bladder,
      and liver cancer. The mechanism of arsenite-induced carcinogenesis is unknown.
      Arsenite is known to disrupt mitosis and to delay transit through M phase in
      normal diploid fibroblasts. SV40-transformed human fibroblasts were observed to
      be hypersensitive to the cytotoxic and cytostatic effects of NaAsO(2) compared
      with normal diploid fibroblasts in concentration-response experiments. Five to 20
      microM NaAsO(2) induced cytostasis in cycling normal diploid fibroblasts but not
      overt lethality in quiescent normal diploid fibroblasts. High concentrations of
      arsenite were overtly lethal in both cycling and quiescent cells. The IC50 for
      cycling SV40-transformed fibroblasts was 3.8 and 4.8 microM for the SV40
      transformed lines GM4429 and GM0637, respectively, whereas, in cycling normal
      diploid fibroblasts (GM0024), the IC50 was 24.7 microM. Microscopic examination
      of NaAsO(2)-treated SV40-transformed fibroblasts suggested a concentration
      dependent accumulation of cells in mitosis undergoing apoptosis. Treatment of
      SV40-transformed fibroblasts with 0-10 microM NaAsO(2) caused a concentration
      dependent inhibition of cell proliferation, accumulation of cells having G2/M DNA
      contents, and increases in the mitotic index. Phase microscopy, annexin V
      binding, and electron microscopy demonstrated that arrested mitotic cells
      underwent apoptosis. These results indicate that SV40-transformation sensitizes
      cells to arsenite-induced mitotic arrest and induction of apoptosis in the
      mitotic cells.

PMID- 11969376
TI  - Roles of oxidative stress and glutathione depletion in JP-8 jet fuel-induced
      apoptosis in rat lung epithelial cells.
AB  - The toxic jet fuel JP-8 induces morphological and biochemical changes
      characteristic of apoptosis in rat lung epithelial (RLE-6TN) cells. The mechanism
      of JP-8 toxicity in these cells was further investigated in an attempt to
      identify potential therapeutic interventions. Given that oxidative stress and
      changes in the concentrations of endogenous antioxidants, such as glutathione
      (GSH), have been associated with the cellular damage elicited by numerous
      toxicants, the possibility that JP-8 induces cellular oxidative stress was
      investigated. Experimentally induced depletion of intracellular GSH or exposure
      of cells to a low concentration of H(2)O(2) markedly enhanced JP-8-induced cell
      death. A significant reduction in intracellular concentrations of GSH was noted
      in RLE-6TN cells shortly after exposure to JP-8. Furthermore, JP-8 induced the
      generation of reactive oxygen species (ROS) in RLE-6TN cells. Consistent with the
      notion that JP-8 toxicity is mediated by generation of ROS and depletion of
      intracellular GSH, JP-8-induced cell death was inhibited by exogenous GSH or the
      thiol-containing antioxidant N-acetyl-cysteine. This protective effect was
      associated with marked inhibition of both the activation of caspase-3 and the
      loss of the mitochondrial membrane potential induced by JP-8. Inhibition of the
      JP-8-induced activation of poly(ADP-ribose) polymerase by 3-aminobenzamide did
      not protect cells against JP-8 toxicity. Together, these results indicate that
      thiol antioxidants are highly effective in rescuing cells from JP-8-induced cell
      death and that they may provide a basis for new therapeutic approaches to
      counteract JP-8 toxicity.

PMID- 11969377
TI  - Pathways of proximal tubular cell death in bismuth nephrotoxicity.
AB  - Colloidal bismuth subcitrate (CBS), a drug for treatment of peptic ulcers, has
      been reported in the literature to be nephrotoxic in humans when taken in high
      overdoses. To investigate the mechanism of bismuth nephropathy, we developed an
      animal model by feeding rats single doses of CBS containing 3.0 mmol Bi/kg body
      weight. Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick
      end labeling assay, immunostaining for active caspase-3, and electron microscopy
      showed that proximal tubular epithelial cells die by necrosis and not by
      apoptosis within 3 h after CBS administration. Exposure of the renal epithelial
      cell lines NRK-52E and LLC-PK1 to Bi(3+) in citrate buffer served as an in vitro
      model of bismuth nephropathy. NRK-52E cells exposed to 100 microM Bi(3+) or more
      died by necrosis, as was demonstrated by nuclear staining with Hoechst 33258 and
      flow cytometry using Alexa(488)-labeled Annexin-V and the vital nuclear dye TOPRO
      3. Bismuth-induced cell death of NRK-52E cells was not prevented by the caspase-3
      inhibitor z-VAD-fmk, whereas this inhibitor did prevent cisplatinum-induced
      apoptosis. Mitochondrial dysfunction and induction of free radicals were shown
      not to be involved in bismuth nephrotoxicity. The early time point of damage
      induction in vitro as well as in vivo and the early displacement of N-cadherin,
      as found in previous studies, suggest that bismuth induces cell death by
      destabilizing the cell membrane. In conclusion, we showed that high overdose of
      bismuth induced cell death by necrosis in vivo as well as in vitro, possibly by
      destabilization of the cell membrane.

PMID- 11969378
TI  - Cytotoxic and endocrine-disrupting potential of atrazine, diazinon, endosulfan,
      and mancozeb in adrenocortical steroidogenic cells of rainbow trout exposed in
      vitro.
AB  - An in vitro bioassay for detection and quantitative assessment of chemicals with
      the capacity to disrupt adrenal steroidogenesis has been developed and used to
      compare the cytotoxic and endocrine-disrupting potential of four pesticides.
      Enzymatically dispersed adrenocortical cells of rainbow trout (Oncorhynchus
      mykiss) were exposed in vitro to atrazine, diazinon, endosulfan, and mancozeb,
      and cortisol secretion in response to ACTH or dibutyryl-cAMP (dbcAMP) and cell
      viability were determined. The effective concentration, EC50 (concentration that
      inhibits cortisol secretion by 50%), the median lethal concentration, LC50
      (concentration that kills 50% of the cells), and the LC50/EC50 ratio were
      established for the test pesticides. The pesticides were ranked as follows: EC50,
      endosulfan < diazinon < mancozeb < atrazine; LC50, diazinon < endosulfan <
      mancozeb < atrazine, with diazinon as the most cytotoxic. Endosulfan and mancozeb
      disrupted sites downstream of the cAMP-generating step of the cortisol synthetic
      pathway while atrazine seemed to act upstream from the cAMP step. The in vitro
      adrenal bioassay can be used for screening of adrenotoxicants and for mechanistic
      studies of adrenotoxicity.

PMID- 11969379
TI  - Role of hypolipidemic drug clofibrate in altering iron regulatory proteins IRP1
      and IRP2 activities and hepatic iron metabolism in rats fed a low-iron diet.
AB  - In addition to reducing the expression of transferrin and ceruloplasmin genes,
      hypolipidemic peroxisome proliferators may alter iron homeostasis in the liver.
      Therefore, this study investigates the effects of clofibrate on proteins related
      to liver iron metabolism in a rat model using a 2 x 2 experimental design: two
      dose levels of clofibrate in diet (0 and 0.5%) and two dietary iron levels (35
      ppm as normal level and 15 ppm as low-iron diet). Twenty-four Wistar rats were
      assigned to the four diets and fed for 6 weeks. Subsequent measurements of iron
      parameters in the blood and the liver indicated that, in addition to mild anemia
      and the reduction in serum iron and total iron-binding capacity, clofibrate
      treatment altered IRP1 and IRP2 activities differentially and increased
      mitochondrial aconitase both at activity and protein levels. At both normal and
      low-iron intakes, clofibrate caused a 50% reduction in serum iron and TIBC with a
      corresponding reduction in transferrin mRNA. The RNA-binding activities of IRP1
      were selectively activated by clofibrate treatment even though liver iron
      concentration was not depleted. The RNA-binding activity of IRP2 was selectively
      activated by the low iron intake and correlated with an increase of transferrin
      receptor mRNA, while clofibrate treatment offset the effects of the low iron
      intake.

PMID- 11969380
TI  - The hidden effect of estrogenic/antiandrogenic methoxychlor on spermatogenesis.
AB  - Perinatal and juvenile oral treatment of rats with methoxychlor (MXC) only during
      development reduces testicular size and Sertoli cell number in those animals as
      adults. The objectives were to determine if MXC administered orally reduces
      numbers of spermatogonia and daily sperm production that parallel reduction in
      Sertoli cell number and if germ cell degeneration rate or function of individual
      Sertoli cells was also affected. Rat dams were gavaged with MXC at 0, 5, 50, or
      150 mg/kg/day for the week before and after they gave birth. Resulting male pups
      (14-16 per group) then were dosed directly from postnatal day 7 to 42. Testes
      were fixed in Bouin's fixative, postfixed in osmium tetroxide, and embedded in
      Epon. Sections of 0.5 and 20 microm were evaluated stereologically. Across dose
      groups, body weight was not affected, but testicular weight was significantly
      reduced in a dose-dependent fashion. Spermatogenic potential based on number of
      spermatogonia and number of spermatids per testis was significantly reduced by
      treatment. There was no adverse effect on daily sperm production per gram of
      parenchyma based on spermatids; however, the number of spermatogonia per gram was
      reduced. The ratio of spermatid number per spermatogonia was higher in the MXC
      treated groups. This difference indicated that the testis can compensate for the
      treatment-induced reduction in number of spermatogonia by reducing degeneration
      of their progeny. However, the reduced number of Sertoli cells prevented the
      compensation from recovering the daily sperm production per testis totally. Given
      that endocrine disruptors like MXC can induce compensation during
      spermatogenesis, it may reduce the ability of the testis to compensate during
      subsequent exposures.

PMID- 11969381
TI  - Dermal application of jet fuel suppresses secondary immune reactions.
AB  - Applying military jet fuel (JP-8) to the skin of mice activates systemic immune
      suppression. In all of our previous experiments, JP-8 was applied to
      immunologically naive mice. The effect of jet fuels on established immune
      reactions, such as immunological memory, is unknown. The focus of the experiments
      presented here was to test the hypothesis that jet fuel exposure [both JP-8 and
      commercial jet fuel (Jet-A)] suppresses established immune reactions. Mice were
      immunized with the opportunistic fungal pathogen Candida albicans and, at
      different times after immunization (10 to 30 days), various doses of undiluted JP
      8 or Jet-A were applied to their skin. Both the elicitation of delayed-type
      hypersensitivity (DTH) (mice challenged 10 days after immunization) and
      immunological memory (mice challenged 30 days after immunization) were
      significantly suppressed in a dose-dependent manner. Dermal exposure to either
      multiple small doses (50 microl over 4 days) or a single large dose
      (approximately 200-300 microl) of JP-8 and/or Jet-A suppressed DTH to C.
      albicans. The mechanism by which dermal application of JP-8 and Jet-A suppresses
      immunological memory involves the release of immune biologic response modifiers.
      Blocking the production of prostaglandin E(2) by a selective cyclooxygenase-2
      inhibitor (SC 236) significantly reversed jet fuel-induced suppression of
      immunologic memory. These findings indicate, for the first time, that dermal
      exposure to commercial jet fuel (Jet-A) suppresses the immune response. In
      addition, the data reported here expand on previous findings by suggesting that
      jet fuel exposure may depress the protective effect of prior vaccination.

PMID- 11969382
TI  - In vivo and in vitro myocardial binding of risperidone and 9-hydroxyrisperidone.
AB  - Antipsychotic drugs have been found to prolong the QT interval, a phenomenon
      that, when severe, may facilitate the occurrence of complex ventricular
      arrhythmia such as torsade de pointes. Concentration-dependent QT prolongation
      has been demonstrated in vitro with such recent drugs as risperidone on Purkinje
      fibers and in isolated feline hearts. In vivo, there appears to be a relationship
      between plasma levels and QTc prolongation. This study was designed to estimate
      cardiac levels in vivo during treatment. For that purpose, we examined both in
      vivo and in vitro the ratio between plasma and cardiac tissue concentrations of
      risperidone and its active metabolite 9-hydroxyrisperidone. Binding parameters
      for different concentrations were determined in vitro by equilibrium dialysis. In
      vivo, they were determined by intraperitoneal administration of three doses in
      the guinea pig. Drug concentrations were determined by a high-performance liquid
      chromatography method with UV detection developed for that purpose. For
      risperidone, plasma protein binding varied from 67 to 43% and cardiac homogenate
      binding varied from 90 to 78%. 9-Hydroxyrisperidone values were lower. Tissue
      levels were 4.5-fold higher than plasma levels. Binding parameters were similar
      both in vivo and in vitro. From this model, the relevance of in vitro
      electrophysiological studies to clinical plasma concentrations can be approached.

PMID- 11969383
TI  - Statistical analysis of the influence of conspecifics on the dispersal of a soil
      collembola.
AB  - The evidence for dispersal activity among soil-living invertebrates comes mainly
      from observations of their movement on artificial substrates or of colonisation
      of defaunated soils in the field. In an attempt to elucidate the dispersal
      pattern of soil collembolans in the presence of conspecifics, statistical
      analyses were undertaken to describe and simulate the movement of groups of
      Onychiurus armatus released in trays of homogeneous soil. A chi(2) test was used
      to reject the null hypothesis that individuals moved independently of each other
      and uniformly in all directions. The mean radial distance moved (1-2 cm day(-1))
      and the radial standard deviation varied temporally and with the density of
      conspecifics. To capture the interaction between the moving individuals, four
      dispersal models (pure diffusion, diffusion with drift interaction, drift
      interaction and synchronised diffusion, and drift interaction and behavioural
      mood), were formulated as stochastic differential equations. The parameters of
      the models were estimated by minimising the deviance between the observed
      replicates and replicates that were simulated using the models. The dynamics of
      movement were best described by modelling the drift interaction as dependent on
      whether individuals were in a social or an asocial mood.

PMID- 11969384
TI  - A persistence criterion for metapopulations.
AB  - Simple conditions to evaluate the persistence of populations living in fragmented
      habitats are of primary importance in ecology. We address this need here using a
      spatially implicit approach that accounts for discrete individuals in a
      metapopulation. Demographic stochasticity is incorporated into a Markovian model
      in a natural way, as local extinction is characterized by the death or the
      dispersal of the last individual inhabiting a patch. The variables of the model
      are the probabilities p(i) (i=0, 1, 2...) that a patch be occupied by a finite,
      integer number i of individuals at a given time. We compare the stationary
      distributions predicted by the model with field data and discuss the role of
      dispersal in determining different distributions of local abundances. The
      analysis of the model leads to a persistence criterion which is equivalent to a
      condition formerly proved by Chesson (Z. Wahrscheinlichkeitstheor. 66, 97-107,
      1984) namely that E(0)>1, where E(0) is the expected number of successful
      dispersers from a patch begun with one individual and to which immigration is
      excluded. We provide an analytic way of computing E(0) as a function of the main
      biological characteristics of the species (natality, mortality and dispersal
      rates, and colonizing ability). We can thus obtain persistence-extinction
      boundaries in the space of model parameters.

PMID- 11969385
TI  - Habitat destruction, environmental catastrophes, and metapopulation extinction.
AB  - The extinction process of fragmented populations, characterized by a small number
      of conspecifics inhabiting each patch, is heavily affected by natural and human
      disturbance. To evaluate the risk of extinction we consider a network of
      identical patches connected by passive or active dispersal and hosting a finite,
      discrete number of individuals. We discuss three types of disturbance affecting
      the metapopulation: permanent loss of habitat patches, erosion of existing
      patches, and random catastrophes that wipe out the entire population of a patch.
      Starting from an infinite-dimensional Markov model that fully accounts for
      demographic stochasticity, we reduce it to finite dimension via moment closure
      with negative-binomial approximation. The compact models obtained in this way
      account for the dynamics of the fraction of empty patches, the average number of
      individuals in occupied patches, and the variance of their distribution. After
      comparing the performance of these compact models with that of the infinite
      dimensional model in the case of no disturbances, we then proceed to computing
      persistence-extinction boundaries as bifurcation lines of the compact models in
      the space of demographic and disturbance parameters. We consider bifurcations
      with respect to demographic and environmental parameters and contrast our results
      with those of previous theories. We find out that environmental catastrophes
      increase the risk of extinction for both frequent and infrequent dispersers,
      while the random loss of patches has a much larger influence on frequent
      dispersers. This influence can be counterbalanced by active dispersal. Local
      erosion of habitat fragments has a larger influence on infrequent than on
      frequent dispersers. We finally discuss the important synergistic effects of
      disturbances acting simultaneously.

PMID- 11969386
TI  - Can we tell how a community was constructed? A comparison of five evenness
      indices for their ability to identify theoretical models of community
      construction.
AB  - Evenness indices provide a simple measure of community structure. It might
      therefore be possible to use them to identify the process by which a community
      has been assembled. To test whether this is practicable, we constructed simulated
      community samples using five stochastic models of community construction,
      proposed by Tokeshi. We then examined the ability of five evenness indices to
      identify the model under which the community samples were produced. Each model
      produced samples with a range of evenness values, but mean evenness differed
      between the models. The dominance decay (DD) model produced community samples
      with the greatest evenness, followed by MacArthur fraction (MF). Evenness was
      lowest under the dominance pre-emption (DP) model. The differences between models
      were quite consistent across indices and consistent between 5-species and 15
      species communities. Samples produced under the DD and MF models varied least in
      evenness between 5-species and 15-species samples, and those produced under the
      random assortment (RA) model varied most, irrespective of the evenness index
      used. Evenness varied considerably between replicate samples, as expected with
      stochastic processes. In 5-species communities, the greatest robustness in
      evenness across replicates was seen using indices O or E'. In 15-species
      communities, O and E(Q) were the most robust. The index best able to identify the
      model which had generated the sample differed between models and with species
      richness. If the model of interest is not known in advance, the best index for
      identifying the generating model is E(var) for communities of more than 10
      species for RF, RA and DP models and O for other communities. The number of
      samples required in a data set before it could be effectively identified was, for
      example, more than 30 for 5-species samples produced under the random fraction
      (RF) model, and 3 for 15-species RF samples. In contrast, a 5-species DD data set
      could be effectively identified when it contained 15 or more samples. We conclude
      that evenness can be used to identify the process by which the community has been
      constructed, out of the five models considered here. The best evenness index for
      doing this varies with the species richness and the evenness of the community but
      we can suggest the use of O without knowing the model because its the more stable
      one against species richness and the more robust and unbiased against simulated
      samples and it encompass a good discriminating power between the models in most
      of the cases studied.

PMID- 11969387
TI  - Likelihood-based disequilibrium mapping for two-marker haplotype data.
AB  - We report a theory that gives the sampling distribution of two-marker haplotypes
      that are linked to a rare disease mutation. The sampling distribution is
      generated with successive Monte Carlo realizations of the coalescence of the
      disease mutation having recombination and marker mutation events placed along the
      lineage. Given a sample of mutation-bearing, two-marker haplotypes, the maximum
      likelihood estimate of the location of the disease mutation can be calculated
      from the generated sampling distribution, provided that one knows enough about
      the population history in order to model it. The two-marker likelihood method is
      compared to a single-marker likelihood and a composite likelihood. The two-marker
      maximum likelihood gives smaller confidence intervals for the location of the
      disease locus than a comparable single-marker maximum likelihood. The composite
      likelihood can give biased results and the bias increases as the extent of
      linkage disequilibrium on mutation-bearing chromosomes decreases. Haplotype
      configurations exist for which the composite likelihood will fail to place the
      disease locus in the correct marker interval.

PMID- 11969388
TI  - On the role of social clusters in the transmission of infectious diseases.
AB  - We introduce a spatial stochastic model for the spread of tuberculosis and HIV.
      We have three parameters: the size of the social cluster for each individual and
      the infection rates within and outside the social cluster. We show that when the
      infection rate from outside the cluster is low (this is presumably the case for
      tuberculosis and HIV) then an epidemic is possible only if the typical social
      cluster and the within infection rate are large enough. These results may be
      important in formulating new hypotheses for the transmission of TB and HIV.

PMID- 11969389
TI  - From asexual to eusocial reproduction by multilevel selection by density
      dependent competitive interactions.
AB  - A game theoretical model is developed to illustrate that multilevel selection by
      density-dependent competitive interactions in mobile organisms might have played
      a major role in the evolutionary transitions from asexual over sexual to eusocial
      reproduction. The model has four equilibria with selection occurring among
      interacting units of respectively one, two, three, and up to infinitely many
      individuals. The different equilibria are characterised by different levels of
      competitive interactions among interacting units, and these levels select for
      different levels of sexual and co-operative reproduction among the individuals of
      the units. The model predicts: (i) that low-energy organisms with negligible body
      masses have asexual reproduction; (ii) that high-energy organisms with non
      negligible body masses in evolutionary equilibria have sexual reproduction
      between a female and a male; (iii) that high-energy organisms with non-negligible
      body masses that increase exponentially at an evolutionary steady state have co
      operative reproduction between a sexual pair and a single sexually produced
      offspring; and (iv) that high-energy organisms with upward constrained body
      masses have eusocial reproduction between a sexual pair and up to an infinite
      number of sexually produced offspring workers.

PMID- 11969390
TI  - Additive genetic variation under intraspecific competition and stabilizing
      selection: a two-locus study.
AB  - A diallelic two-locus model is investigated in which the loci determine the
      genotypic value of a quantitative trait additively. Fitness has two components:
      stabilizing selection on the trait and a frequency-dependent component, as
      induced, for instance, if the ability to utilize different food resources depends
      on this trait. Since intraspecific competition induces disruptive selection, this
      model leads to a conflict of selective forces. We study how the underlying
      genetics (recombination rate and allelic effects) interacts with the selective
      forces, and explore the resulting equilibrium structure. For the special case of
      equal effects, global stability results are proved. Unless the locus effects are
      sufficiently different, the genetic variance maintained at equilibrium displays a
      threshold-like dependence on the strength of competition. For loci with equal
      effects, the equilibrium fitnesses of genotypic values exhibit disruptive
      selection if and only if competition is strong enough to maintain a stable two
      locus polymorphism. For unequal effects, disruptive selection can be observed for
      weaker competition and in the absence of a stable polymorphism.

PMID- 11969391
TI  - Coexistence in MacArthur-style consumer-resource models.
AB  - The nature of and conditions for permanent coexistence of consumers and resources
      are characterized in a family of models that generalize MacArthur's consumer
      resource model. The generalization is of the resource dynamics, which need not be
      of Lotka-Volterra form but are subject only to certain restrictions loose enough
      to admit many resource dynamics of biological interest. For any such model, (1)
      if there is an interior equilibrium, then it is globally attracting, else some
      boundary equilibrium is globally attracting-thus permanent coexistence is
      coexistence at a globally attracting equilibrium; (2) there is an interior
      equilibrium if and only if for any species, the equilibrium approached in the
      absence of that species and the presence of the others is invasible by that
      species--thus permanent coexistence is equivalent to mutual invasibility; (3) for
      resources without direct interactions, the conditions for permanent coexistence
      of the consumers admit an instructive formulation in terms of regression
      statistics. The significance and limitations of the models and results are
      discussed.

PMID- 11969392
TI  - The probability of topological concordance of gene trees and species trees.
AB  - The concordance of gene trees and species trees is reconsidered in detail,
      allowing for samples of arbitrary size to be taken from the species. A sense of
      concordance for gene tree and species tree topologies is clarified, such that if
      the "collapsed gene tree" produced by a gene tree has the same topology as the
      species tree, the gene tree is said to be topologically concordant with the
      species tree. The term speciodendric is introduced to refer to genes whose trees
      are topologically concordant with species trees. For a given three-species
      topology, probabilities of each of the three possible collapsed gene tree
      topologies are given, as are probabilities of monophyletic concordance and
      concordance in the sense of N. Takahata (1989), Genetics 122, 957-966. Increasing
      the sample size is found to increase the probability of topological concordance,
      but a limit exists on how much the topological concordance probability can be
      increased. Suggested sample sizes beyond which this probability can be increased
      only minimally are given. The results are discussed in terms of implications for
      molecular studies of phylogenetics and speciation.

PMID- 11969393
TI  - A combinatorial approach toward analyzing functional elements of the Escherichia
      coli hemolysin signal sequence.
AB  - Secretion of hemolysin is directed by a signal sequence located within its C
      terminal 60 amino acids. Deletion analyses have indicated that the extreme end of
      this C-terminus is critical for transport; however, it is not known if this
      region contains structural features necessary for function. In this study, we
      have used a combinatorial approach to generate two contiguous 8-residue random
      libraries (Cterm1 and Cterm2) in the signal sequence to investigate the
      functional specificity of the last 16 residues. The large number of variants
      generated had provided us with a rich data set to determine if a restricted
      subset of sequences was actually required for function in the extreme C-terminus.
      We observed that over 90% of the random sequences in the Cterm1 region were
      secreted at close to wild-type level, while the Cterm2 region was more restricted
      with only 50% of the random sequences supporting wild-type-like transport. It
      appeared that, in the Cterm2 region, the relative lack of positive charge is
      favored for function. These findings, along with previous results, allow us to
      propose a model for recognition and transport of hemolysin that emphasizes
      secondary structure and general biophysical properties over primary sequence.
      This model may have implications for understanding the broad substrate
      specificity common among ATP-binding cassette transporters.

PMID- 11969394
TI  - Guanidine hydrochloride induced equilibrium unfolding studies of colicin B and
      its channel-forming fragment.
AB  - The conformational stabilities of full-length colicin B and its isolated C
      terminal domain were studied by guanidine hydrochloride induced unfolding. The
      unfolding/refolding was monitored by far-UV CD and intrinsic tryptophan
      fluorescence spectroscopies. At pH 7.4, the disruption of the secondary structure
      of full-length colicin B is monophasic, while changes in tertiary structure occur
      in two separate transitions. The intermediate species, which is well-populated
      around 2.2 M guanidine hydrochloride, exhibits secondary and tertiary structures
      distinct from both native and unfolded states. Whereas the domain structure of
      native full-length colicin B is reflected in its DSC profile, the folding
      intermediate of the same protein exhibits a single unresolved peak. These
      observations have led us to propose an unfolding model for full-length colicin B
      where the first transition between 0 and 2.5 M GuHCl with an associated free
      energy of 3 kcal/mol correlates with the partial unfolding of the R/T domain. The
      stability of full-length colicin B is weakened due to the presence of the R/T
      domain in both the native [Ortega, A., Lambotte, S., and Bechinger, B. (2001) J.
      Biol. Chem. 276 (17), 13563-13572] and the intermediate states. The second
      transition between 2.5 and 5 M GuHCl involves unfolding of the C-terminal domain
      (Delta = 7 kcal/mol). The isolated colicin B C-terminal domain consists of two
      subdomains, and the two parts of this protein fragment unfold sequentially
      through the formation of at least one intermediate. The significance of these
      results for membrane insertion of colicin B is discussed.

PMID- 11969395
TI  - Proton transfers in the photochemical reaction cycle of proteorhodopsin.
AB  - The spectral and photochemical properties of proteorhodopsin (PR) were determined
      to compare its proton transport steps to those of bacteriorhodopsin (BR). Static
      and time-resolved measurements on wild-type PR and several mutants were done in
      the visible and infrared (FTIR and FT-Raman). Assignment of the observed C=O
      stretch bands indicated that Asp-97 and Glu-108 serve as the proton acceptor and
      donor, respectively, to the retinal Schiff base, as do the residues at
      corresponding positions in BR, but there are numerous spectral and kinetic
      differences between the two proteins. There is no detectable dark-adaptation in
      PR, and the chromophore contains nearly entirely all-trans retinal. Because the
      pK(a) of Asp-97 is relatively high (7.1), the proton-transporting photocycle is
      produced only at alkaline pH. It contains at least seven transient states with
      decay times in the range from 10 micros to 200 ms, but the analysis reveals only
      three distinct spectral forms. The first is a red-shifted K-like state. Proton
      release does not occur during the very slow (several milliseconds) rise of the
      second, M-like, intermediate, consistent with lack of the residues facilitating
      extracellular proton release in BR. Proton uptake from the bulk, presumably on
      the cytoplasmic side, takes place prior to release (tau approximately 2 ms), and
      coincident with reprotonation of the retinal Schiff base. The intermediate
      produced by this process contains 13-cis retinal as does the N state of BR, but
      its absorption maximum is red-shifted relative to PR (like the O state of BR).
      The decay of this N-like state is coupled to reisomerization of the retinal to
      all-trans, and produces a state that is O-like in its C-C stretch bands, but has
      an absorption maximum apparently close to that of unphotolyzed PR.

PMID- 11969396
TI  - Maximal stabilities of reversible two-state proteins.
AB  - The hydrophobic effect is the major force driving protein folding. Around room
      temperature, small organic solutes and hydrophobic amino acids have low
      solubilities in water and the hydrophobic effect is the strongest. These facts
      suggest that globular proteins should be maximally stable around room
      temperature. While this fundamental paradigm has been expected, it has not
      actually been shown to hold. Toward this goal, we have collected and analyzed
      experimental thermodynamic data for 31 proteins that show reversible two-state
      folding <--> unfolding transitions at or near neutral pH. Twenty-six of these are
      unique, and 20 of the 26 are maximally stable around room temperature
      irrespective of their structural properties, the melting temperature, or the
      living temperatures of their source organisms. Their average temperature of
      maximal stability is 293 +/- 8 K (20 +/- 8 degrees C). These proteins differ in
      size, fold, and number of domains, hydrophobic folding units, and oligomeric
      states. They derive from the cold-loving psychrophiles, from mesophiles, and from
      thermophiles. Analysis of the single-domain proteins present in this set shows
      that the variations in their thermodynamic parameters are correlated in a way
      which may explain the adaptation of the proteins to the living temperatures of
      the organisms from which they derive. The average energetic contribution of the
      individual amino acids toward protein stability decreases with an increase in
      protein size, suggesting that there may be an upper limit for protein maximal
      thermodynamic stability. For the remaining proteins, deviation of the maximal
      stability temperatures from room temperature may be due to greater uncertainties
      in their heat capacity change (DeltaC(p)) values, a weaker hydrophobic effect,
      and/or a stronger electrostatic contribution.

PMID- 11969397
TI  - Molecular dynamics simulations of mixed micelles modeling human bile.
AB  - Extensive molecular dynamics (MD) simulations of binary systems of phospholipids
      and bile salts, a model for human bile, have been performed. Recent progress in
      hardware and software development allows simulation of the spontaneous
      aggregation of the constituents into small mixed micelles, in agreement with
      experimental observations. The MD simulations reveal the structure of these
      micelles at atomic detail. The phospholipids are packed radially with their
      headgroups at the surface and the hydrophobic tails pointing toward the micellar
      center. The bile salts act as wedges between the phospholipid headgroups, with
      their hydrophilic sides exposed to the aqueous environment. The structure of the
      micelles strongly resembles the previously proposed radial shell model.
      Simulations including small fractions of cholesterol reveal how cholesterol is
      solubilized inside these mixed micelles without changing their overall structure.

PMID- 11969398
TI  - Effect of magnesium ions on the tertiary structure of the hepatitis C virus IRES
      and its affinity for the cyclic peptide antibiotic viomycin.
AB  - A key ion-dependent folding unit within the hepatitis C IRES comprises the IIIef
      junction and pseudoknot. This region is also important in recruitment of the 40S
      ribosomal subunit. Here, circular dichroism is used to study the influence of
      metal ions on the structure and stability of this region. Comparison of the
      thermal stability of an IRES fragment encompassing subdomains IIIe/f and IV
      (named 3EF4) with that of a larger fragment also possessing subdomain IIId
      (3DEF4) indicates an additional stabilizing effect of Mg(2+) ions on the latter
      fragment. Magnesium and potassium ions stabilize both fragments through
      nonspecific counterion effects. The additional effect of magnesium on 3DEF4,
      observed in the absence or presence of 100 mM KCl, is attributed to a nonspecific
      but high-affinity site for metal ions created by a region of unusual high charge
      density. Subdomain IIId presumably participates in tertiary packing interactions
      that provide such a site. Viomycin binds to the full-length IRES and RNA
      fragments with K(d) values of 25-55 microM. Interestingly, viomycin binding to
      the two fragments is affected differently by Mg(2+); noncompetitive inhibition of
      binding to 3DEF4 is observed, whereas binding to 3EF4 is not impaired. Formation
      of a Mg(2+)-stabilized tertiary fold, involving subdomain IIId, may thereby
      hinder viomycin binding to 3DEF4 indirectly. Mutational and deletion studies
      locate viomycin binding within subdomains IIIe/f rather than within the
      pseudoknot. In pseudoknot mutants, Mg(2+) ions have different effects on viomycin
      binding and thermal stability, suggesting altered tertiary interactions involving
      subdomain IIId.

PMID- 11969399
TI  - Potassium-dependent folding: a key to intracellular delivery of G-quartet
      oligonucleotides as HIV inhibitors.
AB  - Several groups have demonstrated that G-rich oligonucleotides forming G-quartet
      structures display activity as potential drugs, such as potent HIV inhibitors.
      The delivery of G-quartet oligonucleotides to their intracellular targets is a
      key obstacle to overcome for their clinical success. Here we have developed a
      novel system to deliver G-rich oligonucleotides into the cell nucleus, e.g., the
      site of HIV integration. On the basis of the property of potassium-induced
      formation of G-quartet structure, we explored the difference of K(+)
      concentrations inside (140 mM) and outside (4 mM) cells to induce the G-rich
      oligonucleotides to form different structures inside and outside cells. The key
      steps of this delivery system include the following: (i) First, the G-quartet
      structure is denatured to form a lipid-DNA complex, so that the molecules can be
      well delivered into cells. (ii) Then the delivered molecules are induced to form
      G-quartet structures by potassium inside cells since the G-quartet structure is
      the primary requirement for inhibition of HIV-1 HIV integrase (IN) activity. The
      molecules of a novel G-quartet HIV inhibitor, T40214, with the sequence of
      (GGGC)(4) were successfully delivered into the nuclei of target cells, which
      significantly decreased HIV-1 replication and increased the probability to target
      HIV-1 IN in infected cells.

PMID- 11969400
TI  - Binding to cisplatin-modified DNA by the Saccharomyces cerevisiae HMGB protein
      Nhp6A.
AB  - Nhp6A is an abundant non-histone chromatin-associated protein in Saccharomyces
      cerevisiae that contains a minor groove DNA binding motif called the HMG box. In
      this report, we show that Nhp6Ap binds to cisplatin intrastrand cross-links on
      duplex DNA with a 40-fold greater affinity than to unmodified DNA with the same
      sequence. Nevertheless, Nhp6Ap bound to cisplatinated DNA readily exchanges onto
      unmodified DNA. Phenanthroline-copper footprinting and two-dimensional NMR on
      complexes of wild-type and mutant Nhp6Ap with DNA were employed to probe the mode
      of binding to the cisplatin lesion. Recognition of the cisplatin adduct requires
      a surface-exposed phenylalanine on Nhp6Ap that promotes bending of DNA by
      inserting into the helix from the minor groove. We propose that Nhp6Ap targets
      the cisplatin adduct by means of intercalation by the phenylalanine and that it
      can bind in either orientation with respect to the DNA lesion. A methionine,
      which also inserts between base pairs and functions in target selection on
      unmodified DNA, plays no apparent role in recognition of the cisplatin lesion.
      Basic amino acids within the N-terminal arm of Nhp6Ap are required for high
      affinity binding to the cisplatin adduct as well as to unmodified DNA. Cisplatin
      mediates its cytotoxicity by forming covalent adducts on DNA, and we find that
      Deltanhp6a/b mutants are hypersensitive to cisplatin in comparison with the wild
      type strain. In contrast, Deltanhp6a/b mutants are slightly more resistant to
      hydrogen peroxide and ultraviolet irradiation. Therefore, Nhp6A/Bp appears to
      directly or indirectly function in yeast to enhance cellular resistance to
      cisplatin.

PMID- 11969401
TI  - Solution structure of the first HMG box domain in human upstream binding factor.
AB  - Human upstream binding factor is a nucleolar transcription factor involved in
      transcription by RNA polymerase I. It contains six HMG box domains; the HMG box
      is a minor groove DNA-binding domain that has been found in hundreds of proteins
      with different functions. Among the six HMG box domains in hUBF, the first one
      can bind to the ribosomal promoter specifically by itself and is essential for
      the whole protein's DNA binding specificity. Here we report the three-dimensional
      structure of this first HMG box free in solution determined by multidimensional
      NMR using (13)C,(15)N-labeled protein. Like the previously determined HMG box
      structures, hUBF HMG box 1 adopts a twisted L-shape consisting of three alpha
      helices: helix 1 (17-30) and helix 2 (38-51) pack onto each other to form the
      short arm, while helix 3 (57-76) is associated with an extended strand N-terminal
      to helix 1 and forms the long arm. A cluster of conserved residues, in particular
      the aromatic residues F21, Y49, and Y60, is important to maintain the fold. The
      short arm is rigid due to extensive hydrophobic interaction between helix 1 and
      helix 2, while the long arm is less rigid.

PMID- 11969402
TI  - The C-terminus and linker region of S100B exert dual control on protein-protein
      interactions with TRTK-12.
AB  - S100B, an EF-hand calcium-binding protein composed of two S100beta monomers,
      undergoes a calcium-dependent conformational change that provides a surface for
      target interactions. In this study, the calcium-sensitive S100B-binding epitope
      TRTK-12 has been used to probe the contributions of the linker and C-terminal
      regions of S100B to protein-protein interactions. These contributions were
      quantified using C-terminal mutant S100B proteins lacking the C-terminal seven
      (S100B85stop) or nine (S100B83stop) residues or containing alanine substitutions
      at Phe87 (F87A), Phe88 (F88A), or both (F8788A). Both F8788A and F88A bound TRTK
      12 less tightly (K(d) = 1.85 +/- 0.02 and 0.97 +/- 0.08 microM, respectively)
      than the wild-type protein (K(d) = 0.27 +/- 0.03 microM, DeltaG = -37.2 kJ/mol),
      indicating these residues are important for TRTK-12 interaction. The truncated
      S100B proteins bound TRTK-12 much more weakly (K(d) = 659.7 +/- 119.3 microM,
      DeltaG = -17.9 kJ/mol), indicating the linker region contributed about 50% to the
      binding of TRTK-12, while the C-terminus contributed the remaining 50% of the
      binding energy. Based on mutagenesis and NMR chemical shift studies, a comparison
      with known S100-target protein complexes showed the S100B-TRTK-12 complex has the
      strongest resemblance to the S100A10-annexin II interaction.

PMID- 11969403
TI  - The two actin-binding regions on the myosin heads of cardiac muscle.
AB  - In the presence of myosin S1 or myosin heads, actin filaments tend to form
      bundles. The biological meaning of the bundling of actin filaments has been
      unclear. In this study, we found that the cardiac myosin heads can form the
      bundles of actin filaments more rapidly than can skeletal S1, as monitored by
      light scattering and electron microscopy. Moreover, the actin bundles formed by
      cardiac S1 were found to be more stable against mechanical agitation. The
      distance between actin filaments in the bundles was approximately 20 nm, which is
      comparable to the length of a myosin head and two actin molecules. This suggests
      the direct binding of S1 tails to the adjacent actin filament. The "essential"
      light chain of cardiac myosin could be cross-linked to the actin molecule in the
      bundle. When monomeric actin molecules were added to the bundle, the bundles
      could be dispersed into individual filaments. The three-dimensional structure of
      the dispersed actin filaments was reconstructed from electron cryo-microscopic
      images of the single actin filaments dispersed by monomer actin. We were able to
      demonstrate that cardiac myosin heads bind to two actin molecules: one actin
      molecule at the conventional actin-binding region and the other at the essential
      light-chain-binding region. This capability of cardiac myosin heads to bind two
      actin molecules is discussed in view of lower ATPase activity and slower
      shortening velocity than those of skeletal ones.

PMID- 11969404
TI  - Cation- and peptide-binding properties of human calmodulin-like skin protein.
AB  - Human CLSP, a new Ca(2+)-binding protein specifically expressed in differentiated
      keratinocytes, is a 15.9 kDa, four EF-hand containing protein with 52% sequence
      identity to calmodulin (CaM). The protein binds four Ca(2+) ions at two pairs of
      sites with [Ca(2+)](0.5) values of 1.2 and 150 microM, respectively. Mg(2+) at
      millimolar concentrations strongly decreases the affinity for Ca(2+) of the two
      high-affinity sites, but has no effect on the low-affinity sites. The protein can
      also bind two Mg(2+) ([Mg(2+)](0.5) = 57 microM) at the sites of high Ca(2+)
      affinity. Thus, as fast skeletal muscle troponin C (TnC), CLSP possesses two high
      affinity Ca(2+)-Mg(2+) mixed sites and two low-affinity Ca(2+)-specific sites.
      Studies on the isolated recombinant N- (N-CLSP) and C-terminal half domains of
      CLSP (C-CLSP) revealed that, in contrast to the case of TNC, the high-affinity
      Ca(2+)-Mg(2+) mixed sites reside in the N-terminal half. The binding of cations
      modifies the intrinsic fluorescence of the two Tyr residues. Upon Ca(2+) binding,
      hydrophobicity is exposed at the protein surface that can be monitored with a
      fluorescent probe. The Ca(2+)-dependency of the two conformational changes is
      biphasic in the absence of Mg(2+), but monophasic in the presence of 2 mM Mg(2+),
      both corresponding closely to direct binding of Ca(2+) to CLSP. In the presence
      of Ca(2+), human CLSP forms a high-affinity 1:1 complex with melittin, a natural
      peptide considered to be a model for the interaction of CaM with its targets. In
      the complex, CLSP binds Ca(2+) with high affinity to all four binding sites.
      Isolated N- and C-CLSP show only a weak interaction with melittin, which is
      enhanced when both halves are simultaneously presented to the model peptide.

PMID- 11969405
TI  - Probing domain swapping for the neuronal SNARE complex with electron paramagnetic
      resonance.
AB  - Highly conserved soluble N-ethylmaleimide sensitive factor attachment protein
      receptor (SNARE) proteins control membrane fusion at synapses. The target plasma
      membrane-associated SNARE proteins and the vesicle-associated SNARE protein
      assemble into a parallel four-helix bundle. Using a novel EPR approach, it is
      found that the SNARE four-helix bundles are interconnected via domain swapping
      that is achieved by substituting one of the two SNAP-25 helices with the
      identical helix from the second four-helical bundle. Domain swapping is likely to
      play a role in the multimerization of the SNARE complex that is required for
      successful membrane fusion. The new EPR application employed here should be
      useful to study other polymerizing proteins.

PMID- 11969406
TI  - Titration and exchange studies of liver fatty acid-binding protein with 13C
      labeled long-chain fatty acids.
AB  - Uniformly (13)C-labeled long-chain fatty acids were used to probe ligand binding
      to rat liver fatty acid-binding protein (LFABP), an atypical member of the fatty
      acid-binding protein (FABP) family that binds more than one molecule of long
      chain fatty acid, accommodates a variety of diverse ligands, and exhibits
      diffusion-mediated lipid transport to membranes. Two sets of (1)H-(13)C
      resonances were found in a titration series of NMR spectra for oleate-LFABP
      complexes, indicating that two molecules of the fatty acid are situated in the
      protein cavity. However, no distinct resonances were observed for the excess
      fatty acid in solution, suggesting that at least one ligand undergoes rapid
      exchange with oleate in the bulk solution. An exchange rate of 54 +/- 6 s(-1)
      between the two sets of resonances was measured directly using (13)C z,z-exchange
      spectroscopy. In light of these NMR measurements, possible molecular mechanisms
      for the ligand-exchange process are evaluated and implications for the anomalous
      fatty acid transport mechanism of LFABP are discussed.

PMID- 11969407
TI  - Mispairing of the 8,9-dihydro-8-(N7-guanyl)-9-hydroxy-aflatoxin B1 adduct with
      deoxyadenosine results in extrusion of the mismatched dA toward the major groove.
AB  - The G --> T transversion is the dominant mutation induced by the cationic trans
      8,9-dihydro-8-(N7-guanyl)-9-hydroxy-aflatoxin B(1) adduct. The structure of
      d(ACATC(AFB)GATCT).d(AGATAGATGT), in which the cationic adduct was mismatched
      with deoxyadenosine, was refined using molecular dynamics calculations restrained
      by NOE data and dihedral restraints obtained from NMR spectroscopy. Restrained
      molecular dynamics calculations refined structures with pairwise rmsd <1 A and a
      sixth root R1x factor between the refined structure and NOE data of 10.5 x 10-2.
      The mismatched duplex existed in a single conformation at neutral pH. The
      aflatoxin moiety intercalated above the 5' face of the modified (AFB)G. The
      mismatched dA was in the anti conformation about the glycosyl bond. It extruded
      toward the major groove and did not participate in hydrogen bonding with (AFB)G.
      The structure was compared with that of d(ACATCGATCT).d(AGATAGATGT) containing
      the corresponding unmodified G.A mismatch and with
      d(ACATC(AFB)GATCT).d(AGATCGATGT) containing the aflatoxin lesion in the correctly
      paired (AFB)G.C context. The correctly paired oligodeoxynucleotide exhibited
      Watson-Crick-type geometry at the (AFB)G.C pair. It melted at higher temperature
      than the mismatched (AFB)G.A duplex. The unmodified mismatched G.A duplex
      exhibited spectral line broadening at neutral pH, suggesting a mixture of
      conformations. It exhibited a lower melting temperature than did the mismatched
      (AFB)G.A duplex. These differences correlated with replication bypass experiments
      performed in vitro utilizing DNA polymerase I exo- [Johnston, D. S., and Stone,
      M. P. (2000) Chem. Res. Toxicol. 13, 1158-1164]. Those experiments showed that
      correct insertion of dC opposite (AFB)G blocked replication by the enzyme,
      whereas incorrect insertion of dA opposite (AFB)G allowed full-length replication
      of the adducted template strand.

PMID- 11969408
TI  - Molecular differences caused by differentiation of 3T3-L1 preadipocytes in the
      presence of either dehydroepiandrosterone (DHEA) or 7-oxo-DHEA.
AB  - The effects of dehydroepiandrosterone (DHEA) and 7-oxo-DHEA on the cell size,
      adiposity, and fatty acid composition of differentiating 3T3-L1 preadipocyte
      cells are correlated with stearoyl-CoA desaturase (SCD) expression (mRNA and
      protein levels) and enzyme activity. Fluorescence-activated cell sorting shows
      that preadipocyte cells treated with methylisobutylxanthine, dexamethasone, and
      insulin (MDI) plus DHEA comprise a population distribution of predominantly large
      cells with reduced adiposity. In contrast, cells treated with MDI plus 7-oxo-DHEA
      comprise a population distribution of almost equal proportions of small and large
      cells that have an adiposity equivalent to cells differentiated with MDI alone.
      The cells treated with MDI plus DHEA have significantly reduced levels of total
      fatty acid, mainly due to a dramatic reduction in the level of palmitoleic
      (Delta(9)-16:1) acid. The cells treated with MDI plus 7-oxo-DHEA have a
      significantly increased level of total fat, primarily due to increased levels of
      Delta(9)-16:1 and palmitic (16:0) acids. At the molecular level, the DHEA-treated
      cells contain lowered amounts of SCD1 mRNA and antibody-detectable desaturase
      protein, while 7-oxo-DHEA-treated cells contained elevated levels of SCD1 mRNA
      and protein. Inhibition of differentiation in DHEA-treated cells was also
      suggested by a reduction in the mRNA level of the adipogenic gene aP2. At the
      level of microsomal enzymatic activity, SCD activity was decreased in DHEA
      treated cells while the SCD activity was increased in 7-oxo-DHEA-treated cells.
      The changes in mRNA levels and enzyme activity were concentration-dependent and
      appeared as early as day 3 of the differentiation protocol. The results show that
      DHEA and 7-oxo-DHEA have distinct modes of action with respect to the complex
      transcriptional cascade required for differentiation. Furthermore, differences in
      the insulin-stimulated uptake of 2-deoxyglucose and in the activity of carnitine
      palmitoyl transferase observed from either DHEA- or 7-oxo-DHEA-treated cells
      support the ability of DHEA to produce a thermogenic effect in differentiating
      preadipocytes, while 7-oxo-DHEA promotes differentiation without other changes
      typical of thermogenesis.

PMID- 11969409
TI  - Prime site binding inhibitors of a serine protease: NS3/4A of hepatitis C virus.
AB  - Serine proteases are the most studied class of proteolytic enzymes and a primary
      target for drug discovery. Despite the large number of inhibitors developed so
      far, very few make contact with the prime site of the enzyme, which constitutes
      an almost untapped opportunity for drug design. In the course of our studies on
      the serine protease NS3/4A of hepatitis C virus (HCV), we found that this enzyme
      is an excellent example of both the opportunities and the challenges of such
      design. We had previously reported on two classes of peptide inhibitors of the
      enzyme: (a) product inhibitors, which include the P(6)-P(1) region of the
      substrate and derive much of their binding energy from binding of their C
      terminal carboxylate in the active site, and (b) decapeptide inhibitors, which
      span the S(6)-S(4)' subsites of the enzyme, whose P(2)'-P(4)' tripeptide fragment
      crucially contributes to potency. Here we report on further work, which combined
      the key binding elements of the two series and led to the development of
      inhibitors binding exclusively to the prime site of NS3/4A. We prepared a small
      combinatorial library of tripeptides, capped with a variety of constrained and
      unconstrained diacids. The SAR was derived from multiple analogues of the initial
      micromolar lead. Binding of the inhibitor(s) to the enzyme was further
      characterized by circular dichroism, site-directed mutagenesis, a probe
      displacement assay, and NMR to unequivocally prove that, according to our design,
      the bound inhibitor(s) occupies (occupy) the S' subsite and the active site of
      the protease. In addition, on the basis of the information collected, the
      tripeptide series was evolved toward reduced peptide character, reduced molecular
      weight, and higher potency. Beyond their interest as HCV antivirals, these
      compounds represent the first example of prime site inhibitors of a serine
      protease. We further suggest that the design of an inhibitor with an analogous
      binding mode may be possible for other serine proteases.

PMID- 11969410
TI  - Dimers to doughnuts: redox-sensitive oligomerization of 2-cysteine
      peroxiredoxins.
AB  - 2-Cys peroxiredoxins (Prxs) are a large and diverse family of peroxidases which,
      in addition to their antioxidant functions, regulate cell signaling pathways,
      apoptosis, and differentiation. These enzymes are obligate homodimers (alpha(2)),
      utilizing a unique intermolecular redox-active disulfide center for the reduction
      of peroxides, and are known to form two oligomeric states: individual alpha(2)
      dimers or doughnut-shaped (alpha(2))(5) decamers. Here we characterize both the
      oligomerization properties and crystal structure of a bacterial 2-Cys Prx,
      Salmonella typhimurium AhpC. Analytical ultracentrifugation and dynamic light
      scattering show that AhpC's oligomeric state is redox linked, with oxidization
      favoring the dimeric state. The 2.5 A resolution crystal structure (R = 18.5%,
      R(free) = 23.9%) of oxidized, decameric AhpC reveals a metastable oligomerization
      intermediate, allowing us to identify a loop that adopts distinct conformations
      associated with decameric and dimeric states, with disulfide bond formation
      favoring the latter. This molecular switch contains the peroxidatic cysteine and
      acts to buttress the oligomerization interface in the reduced, decameric enzyme.
      A structurally detailed catalytic cycle incorporating these ideas and linking
      activity to oligomeric state is presented. Finally, on the basis of sequence
      comparisons, we suggest that the enzymatic and signaling activities of all 2-Cys
      Prxs are regulated by a redox-sensitive dimer to decamer transition.

PMID- 11969411
TI  - The C terminus of apocytochrome b562 undergoes fast motions and slow exchange
      among ordered conformations resembling the folded state.
AB  - The present work describes the dynamics of the apo form of cytochrome b(562), a
      small soluble protein consisting of 106 amino acid residues [Itagaki, E., and
      Hager, L. P. (1966) J. Biol. Chem. 241, 3687-3695]. The presence of exchange in
      the millisecond time scale is demonstrated for the last part of helix IV
      (residues 95-105 in the holo form). The chemical shift index analysis [Wishart,
      D. S., and Sykes, B. D. (1994) J. Biomol. NMR 4, 171-180] based on H(alpha),
      C(alpha), C(beta), and C' chemical shifts suggests a larger helical content than
      shown in the NMR structure based on NOEs. These results indicate the presence of
      helical-like conformations participating in the exchange process. This hypothesis
      is consistent with amide deuterium exchange rates and the presence of some
      hydrogen bonds identified from amide chemical shift temperature coefficients
      [Baxter, N. J., and Williamson, M. P. (1997) J. Biomol. NMR 9, 359-369]. (15)N
      relaxation indicates limited mobility for the amide protons of this part of the
      helix in the picosecond time scale. A 30 ns stochastic dynamics simulation shows
      small fluctuations around the helical conformation on this time scale. These
      fluctuations, however, do not result in a significant decrease of the calculated
      order parameters which are consistent with the experimental (15)N relaxation
      data. These results resolve an apparent discrepancy in the NMR structures between
      the disorder observed in helix IV due to a lack of NOEs and the secondary
      structure predictions based on H(alpha) chemical shifts [Feng, Y., Wand, A. J.,
      and Sligar, S. G. (1994) Struct. Biol. 1, 30-35].

PMID- 11969412
TI  - Structure and dynamics of a beta-helical antifreeze protein.
AB  - Antifreeze proteins (AFPs) protect many types of organisms from damage caused by
      freezing. They do this by binding to the ice surface, which causes inhibition of
      ice crystal growth. However, the molecular mechanism of ice binding leading to
      growth inhibition is not well understood. In this paper, we present the solution
      structure and backbone NMR relaxation data of the antifreeze protein from the
      yellow mealworm beetle Tenebrio molitor (TmAFP) to study the dynamics in the
      context of structure. The full (15)N relaxation analysis was completed at two
      magnetic field strengths, 500 and 600 MHz, as well as at two temperatures, 30 and
      5 degrees C, to measure the dynamic changes that occur in the protein backbone at
      different temperatures. TmAFP is a small, highly disulfide-bonded, right-handed
      parallel beta-helix consisting of seven tandemly repeated 12-amino acid loops.
      The backbone relaxation data displays a periodic pattern, which reflects both the
      12-amino acid structural repeat and the highly anisotropic nature of the protein.
      Analysis of the (15)N relaxation parameters shows that TmAFP is a well-defined,
      rigid structure, and the extracted parameters show that there is similar
      restricted internal mobility throughout the protein backbone at both temperatures
      studied. We conclude that the hydrophobic, rigid binding site may reduce the
      entropic penalty for the binding of the protein to ice. The beta-helical fold of
      the protein provides this rigidity, as it does not appear to be a consequence of
      cooling toward a physiologically relevant temperature.

PMID- 11969413
TI  - Structure-based design of potent histatin analogues.
AB  - Conformational studies of human salivary peptide, histatin 3 (Hst3), were
      performed by nuclear magnetic resonance (NMR) and circular dichroism (CD)
      spectroscopy in a membrane-mimicking environment. The structural information that
      was obtained was used in the design of peptide analogues with improved antifungal
      activity. In the presence of increasing concentrations of L-alpha
      dimyristoylphosphatidylcholine (L-alpha-DMPC) lipid vesicles, a dramatic increase
      in a minimum at 198 nm is observed in the CD spectra of Hst3. The NMR data of
      Hst3 in the presence of L-alpha-DMPC lipid vesicles reveal the proximity of
      residues Y(10) and S(20), indicating the existence of a more compact structure.
      Peptide analogues were designed on the basis of this observation, which
      incorporated a disulfide bond to stabilize an extended loop in this region of the
      sequence. One of these, peptide 4, was 100 times more potent than Hst5 against
      Saccharomyces cerevisiae cells. Conformational analysis of peptide 4 revealed a
      looped structure with charged residues protruding on the outside surface, while a
      combination of aromatic residues and histidines are packed into an internal core.

PMID- 11969414
TI  - Structure of Ala24/Asp61 --> Asp24/Asn61 substituted subunit c of Escherichia
      coli ATP synthase: implications for the mechanism of proton transport and rotary
      movement in the F0 complex.
AB  - The structure of the A24D/D61N substituted subunit c of Escherichia coli ATP
      synthase, in which the essential carboxylate has been switched from residue 61 of
      the second transmembrane helix (TMH) to residue 24 of the first TMH, has been
      determined by heteronuclear multidimensional NMR in a monophasic
      chloroform/methanol/water (4:4:1) solvent mixture. As in the case of the wild
      type protein, A24D/D61N substituted subunit c forms a hairpin of two extended
      alpha-helices (residues 5-39 and 46-78), with residues 40-45 forming a connecting
      loop at the center of the protein. The structure was determined at pH 5, where
      Asp24 is fully protonated. The relative orientation of the two extended helices
      in the A24D/D61N structure is different from that in the protonated form of the
      wild-type protein, also determined at pH 5. The C-terminal helix is rotated by
      150 degrees relative to the wild-type structure, and the N-terminal helix is
      rotated such that the essential Asp24 carboxyl group packs on the same side of
      the molecule as Asp61 in the wild-type protein. The changes in helix-helix
      orientation lead to a structure that is quite similar to that of the deprotonated
      form of wild-type subunit c, determined at pH 8. When a decameric ring of c
      subunits was modeled from the new structure, the Asp24 carboxyl group was found
      to pack in a cavity at the interface between two subunits that is similar to the
      cavity in which Asp61 of the wild-type protein is predicted to pack. The
      interacting faces of the packed subunits in this model are also similar to those
      in the wild-type model. The results provide further evidence that subunit c is
      likely to fold in at least two conformational states differing most notably in
      the orientation of the C-terminal helix. Based upon the structure, a mechanistic
      model is discussed that indicates how the wild-type and A24D/D61N subunits could
      utilize similar helical movements during H(+) transport-coupled rotation of the
      decameric c ring.

PMID- 11969415
TI  - Structure of the transition state of gating in the acetylcholine receptor channel
      pore: a phi-value analysis.
AB  - The gating mechanism of the acetylcholine receptor channel (AChR) was
      investigated by using rate equilibrium linear free energy relationships (LFERs)
      to probe the transition state between the closed and open conformations. The
      properties of the transition state of gating in the second transmembrane segment
      (M2) of the delta subunit, one of the five homologous pore-lining segments, was
      measured on a residue-by-residue basis. Series of point mutations were engineered
      at individual positions of this domain, and the corresponding constructs were
      characterized electrophysiologically, at the single-channel level. Fully liganded
      AChR opening and closing rate constants were estimated, and Phi-values (which are
      a measure of the extent of the conformational change realized at the transition
      state) were calculated for each reaction series as the slope of the Bronsted
      relationship (log rate constant versus log equilibrium constant). Our results
      indicate that, at the transition state of gating, the extracellular half of
      deltaM2 partly resembles the open state (Phi-values between 0.24 and 0.38) while
      the intracellular half completely resembles the closed state (Phi-values between 
      0.18 and 0.03), with a break point near the middle of the M2 segment. This
      suggests that during gating the two halves of deltaM2 move asynchronously, with
      the rearrangement of the extracellular portion preceding (following) that of the
      intracellular part of deltaM2 during opening (closing). This particular sequence
      of molecular events indicates that the gating conformational change, which starts
      at the extracellular acetylcholine-binding sites (when opening), does not
      propagate exclusively along the primary sequence of the protein. In addition, our
      data are consistent with the deltaM2 segment bending or swiveling around its
      central residues during gating. We also elaborate on unsettled aspects of the
      analysis such as the accuracy of two-point LFERs, the physical interpretation of
      fractional Phi-values, and the existence of single versus parallel transition
      states for the gating reaction.

PMID- 11969416
TI  - Binding of enzyme IIAGlc, a component of the phosphoenolpyruvate:sugar
      phosphotransferase system, to the Escherichia coli lactose permease.
AB  - Enzyme IIA(Glc), encoded by the crr gene of the phosphoenolpyruvate:sugar
      phosphotransferase system, plays an important role in regulating intermediary
      metabolism in Escherichia coli ("catabolite repression"). One function involves
      inhibition of inducible transport systems ("inducer exclusion"), and with lactose
      permease, a galactoside is required for unphosphorylated IIA(Glc) binding to
      cytoplasmic loops IV/V and VI/VII [Sondej, M., Sun, J. et al. (1999) Proc. Natl.
      Acad. Sci. U.S.A. 96, 3525-3530]. With inside-out membrane vesicles containing
      the permease, [(125)I]IIA(Glc) binding promoted by melibiose exhibits an affinity
      (K(D)(IIA)) of approximately 1 microM and a stoichiometry of one mole of IIA(Glc)
      per six moles of lactose permease. Both the quantity of [(125)I]IIA(Glc) bound
      and the sugar concentration required for half-maximal IIA(Glc) binding
      (K(0.5)(IIA)(sug)) was measured for eight permease substrates. Differences in
      maximal IIA(Glc) binding are observed, and the K(0.5)(IIA)(sug) does not
      correlate with the affinity of LacY for sugar. Furthermore, K(0.5)(IIA)(sug) does
      not correlate with sugar affinities for various permease mutants. IIA(Glc) does
      not bind to a mutant (Cys154 --> Gly), which is locked in an outwardly facing
      conformation, binds with increased stoichiometry to mutant Lys131 --> Cys, and
      binds only weakly to two other mutants which appear to be predominantly in either
      an outwardly or an inwardly facing conformation. When the latter two mutations
      are combined, sugar-dependent IIA(Glc) binding returns to near wild-type levels.
      The findings suggest that binding of various substrates to lactose permease
      results in a collection of unique conformations, each of which presents a
      specific surface toward the inner face of the membrane that can interact to
      varying degrees with IIA(Glc).

PMID- 11969417
TI  - Phosphorylation-dependent interaction of kinesin light chain 2 and the 14-3-3
      protein.
AB  - The protein 14-3-3 is a key regulator in a cell signaling pathway mediated by
      protein phosphorylation. To identify the cellular targets of this protein
      systematically, we have employed a proteomic approach: protein components pulled
      down from PC12 cells stably expressing a myc-tagged 14-3-3eta isoform were
      analyzed by means of SDS-PAGE and mass spectrometry. This procedure allowed us to
      identify more than 30 proteins that include various known and unknown targets of
      the 14-3-3 protein. Among them are several proteins in the membrane traffic
      pathway, such as the heavy and light chains (KHC/KIF5B and KLC2) of conventional
      kinesin, a heterotetrameric mechanochemical motor involved in the ATP-dependent
      movement of vesicles and organelles along microtubules. Subsequent analysis
      showed that 14-3-3 directly binds to kinesin heterodimers through interaction
      with KLC2 and that this interaction is dependent on the phosphorylation of KLC2.
      Studies on the interaction between 14-3-3 and KLC2 variants expressed in cultured
      cells coupled with mass spectrometric analysis proved that Ser575 is the site of
      phosphorylation in KLC2 that is responsible for the in vivo interaction with the
      14-3-3 protein. These data add KLC2 to the growing list of 14-3-3 targets, and
      suggest a role of 14-3-3 in the phosphorylation-regulated cellular transport of
      vesicles and organelles.

PMID- 11969418
TI  - SecA specificity for different signal peptides.
AB  - SecA performs a critical function in the recognition, targeting, and transport of
      secretory proteins across the cytoplasmic membrane of Escherichia coli. In this
      study we investigate the substrate specificity of SecA, including the influence
      of the early mature region of the preprotein on SecA interactions, and the extent
      to which SecA recognizes targeting signals from different transport pathways. A
      series of fusion proteins were generated which involved the tandem expression of
      GST, signal peptide, and the first 30 residues from alkaline phosphatase. These
      were purified and evaluated for their ability to promote SecA ATPase activity. No
      significant difference in the stimulation of SecA-lipid ATPase activity between
      the synthetic wild-type alkaline phosphatase signal peptide and a fusion that
      also contains the first 30 residues of alkaline phosphatase was observed. The
      incorporation of sequence motifs in the mature region, which confer SecB
      dependence in vivo, had no impact on SecA activation in vitro. These results
      suggest that the early mature region of alkaline phosphatase does not affect the
      interactions between SecA and the signal peptide. Sec, Tat, and YidC signal
      peptide fusions were also assayed for their ability to stimulate SecA ATPase
      activity in vitro and further analyzed in vivo for the Sec dependence of the
      transport of the corresponding signal peptide mutants of alkaline phosphatase.
      Our results demonstrate that E. coli Sec signals give the highest level of SecA
      activation; however, SecA-signal peptide interactions in vitro are not the only
      arbiter of whether the preprotein utilizes the Sec pathway in vivo.

PMID- 11969419
TI  - All of the protein interactions that link steroid receptor.hsp90.immunophilin
      heterocomplexes to cytoplasmic dynein are common to plant and animal cells.
AB  - Both plant and animal cells contain high molecular weight immunophilins that bind
      via tetratricopeptide repeat (TPR) domains to a TPR acceptor site on the
      ubiquitous and essential protein chaperone hsp90. These hsp90-binding
      immunophilins possess the signature peptidylprolyl isomerase (PPIase) domain, but
      no role for their PPIase activity in protein folding has been demonstrated. From
      the study of glucocorticoid receptor (GR).hsp90.immunophilin complexes in
      mammalian cells, there is considerable evidence that both hsp90 and the FK506
      binding immunophilin FKBP52 play a role in receptor movement from the cytoplasm
      to the nucleus. The role of FKBP52 is to target the GR.hsp90 complex to the
      nucleus by binding via its PPIase domain to cytoplasmic dynein, the motor protein
      responsible for retrograde movement along microtubules. Here, we use rabbit
      cytoplasmic dynein as a surrogate for the plant homologue to show that two hsp90
      binding immunophilins of wheat, wFKBP73 and wFKBP77, bind to dynein. Binding to
      dynein is blocked by competition with a purified FKBP52 fragment comprising its
      PPIase domain but is not affected by the immunosuppressant drug FK506, suggesting
      that the PPIase domain but not PPIase activity is involved in dynein binding. The
      hsp90/hsp70-based chaperone system of wheat germ lysate assembles complexes
      between mouse GR and wheat hsp90. These receptor heterocomplexes contain wheat
      FKBPs, and they bind rabbit cytoplasmic dynein in a PPIase domain-specific
      manner. Retention by plants of the entire heterocomplex assembly machinery for
      linking the GR to dynein implies a fundamental role for this process in the
      biology of the eukaryotic cell.

PMID- 11969420
TI  - Cooperativity and oligomeric status of cardiac muscarinic cholinergic receptors.
AB  - Muscarinic cholinergic receptors can appear to be more numerous when labeled by
      [(3)H]quinuclidinylbenzilate (QNB) than by N-[(3)H]methylscopolamine (NMS). The
      nature of the implied heterogeneity has been studied with M(2) receptors in
      detergent-solubilized extracts of porcine atria. The relative capacity for
      [(3)H]NMS and [(3)H]QNB was about 1 in digitonin-cholate, 0.56 in cholate-NaCl,
      and 0.44 in Lubrol-PX. Adding digitonin to extracts in cholate-NaCl increased the
      absolute capacity for both radioligands, and the relative capacity increased to
      near 1. The latency cannot be attributed to a chemically impure radioligand,
      instability of the receptor, an irreversible effect of NMS, or a failure to reach
      equilibrium. Binding at near-saturating concentrations of [(3)H]QNB in cholate
      NaCl or Lubrol-PX was blocked fully by unlabeled NMS, which therefore appeared to
      inhibit noncompetitively at sites inaccessible to radiolabeled NMS. Such an
      effect is inconsistent with the notion of functionally distinct,
      noninterconverting, and mutually independent sites. Both the noncompetitive
      effect of NMS on [(3)H]QNB and the shortfall in capacity for [(3)H]NMS can be
      described quantitatively in terms of cooperative interactions within a receptor
      that is at least tetravalent; no comparable agreement is possible with a receptor
      that is only di- or trivalent. The M(2) muscarinic receptor therefore appears to
      comprise at least four interacting sites, presumably within a tetramer or larger
      array, and ligands appear to bind in a cooperative manner under at least some
      conditions.

PMID- 11969421
TI  - Transbilayer movement of fluorescent phospholipid analogues in the cytoplasmic
      membrane of Escherichia coli.
AB  - We investigated the transmembrane movement of fluorescent labeled phospholipids
      in inverted inner membrane vesicles (IIMV) of Escherichia coli (E. coli) wild
      type strain (MG1655), as well as in proteoliposomes reconstituted from detergent
      extracts of the IIMV. The transbilayer movement of 1-myristoyl-2-[6-[(7-nitro
      2,1,3-benzoxadiazol-4-yl)amino]caproyl]-sn-glycero-3-phosphoethanolamine (M-C6
      NBD-PE) and -phosphocholine (M-C6-NBD-PC) was measured by a fluorescence stopped
      flow back-exchange assay. Both analogues were rapidly translocated across the
      IIMV membrane, with half-times of <1 min (outward movement) and approximately 3
      min (inward movement). No flip-flop was detected in protein-free liposomes, but
      in IIMV-derived proteoliposomes flip-flop of M-C6-NBD-PE occurred similarly to
      IIMV and could be largely eliminated by proteinase K treatment.

PMID- 11969422
TI  - Identification of in vivo phosphorylation sites of MLK3 by mass spectrometry and
      phosphopeptide mapping.
AB  - MLK3 is a serine/threonine protein kinase that functions as an upstream activator
      of the JNK pathway. Previous work has suggested that MLK3 is a
      multiphosphorylated protein. In this study, mass spectrometry coupled with
      comparative phosphopeptide mapping was used to directly characterize MLK3 in vivo
      phosphorylation sites. Various types of mass spectrometry were used to analyze
      MLK3 tryptic peptides separated by C18 reverse-phase HPLC, leading to the
      identification of Ser(524), Ser(654), Ser(705), Ser(740), Ser(758), Ser(770),
      Ser(793), and a site found on peptide Ser(11)-Arg(37) within a Gly-rich region as
      MLK3 phosphorylation sites. Additionally, porous graphitic carbon chromatography
      successfully retained and resolved phosphopeptides that had eluted along with
      nonvolatile salts and buffers in the flowthrough fractions from the C18 column.
      Following resolution by PGC chromatography, MALDI-MS in conjunction with alkaline
      phosphatase treatment identified Ser(555), Ser(556), Ser(724), and Ser(727) as
      sites of phosphorylation on MLK3. A proline residue immediately follows 7 of the
      11 unambiguously identified phosphorylation sites, suggesting that MLK3 may be a
      target of proline-directed kinases. Finally, two-dimensional phosphopeptide
      mapping confirmed that phosphorylation of Ser(555) and Ser(556) of MLK3 is
      induced by the activated small GTPase Cdc42.

PMID- 11969423
TI  - Identification of potential physiological activators of protein phosphatase 5.
AB  - The protein serine/threonine phosphatase designated PP5 has little basal
      activity, and physiological activators of the enzyme have never been identified.
      Purified PP5 can, however, be activated by partial proteolysis or by the binding
      of supraphysiological concentrations of polyunsaturated long-chain fatty acids to
      its tetratricopeptide repeat (TPR) domain. To test whether activation of PP5 by
      polyunsaturated but not saturated fatty acids was an artifact of the lower
      solubility of saturated fatty acids, the effects of fatty acyl-CoA esters were
      examined. Saturated and unsaturated long-chain fatty acids are both freely water
      soluble when esterified to CoA. Long-chain fatty acyl-CoA esters activated PP5 at
      physiological concentrations, with the saturated compounds being more effective.
      We investigated the effects of chain length and of the CoA moiety on PP5
      activation. Chains of 16 carbons or more were required for optimal activation,
      with no activation observed below 10 carbons. On the basis of competition studies
      using acetyl-CoA, the function of the CoA moiety appeared to be to increase
      solubility of the fatty acyl moiety rather than to interact with a specific
      binding site. These data suggested that long-chain fatty acid-CoA esters might be
      physiological activators of PP5 and point to a potential link between fatty acid
      metabolism and signal transduction via this enzyme. Because heat shock protein 90
      is also known to bind to the TPR domain of PP5 via its C-terminal domain (C90),
      we investigated its effect on PP5 activity. C90 activated the enzyme
      approximately 10-fold. Thus, we have identified two potential physiological
      activators of PP5.

PMID- 11969424
TI  - Oxidation of 10-formyltetrahydrofolate to 10-formyldihydrofolate by complex IV of
      rat mitochondria.
AB  - We hypothesized that the unanticipated bioactivity of orally administered
      unnatural carbon-6 isomers, (6R)-5-formyltetrahydrofolate (5-HCO-THF) and (6S)
      5,10-methenyltetrahydrofolate (5,10-CH-THF), in humans [Baggott, J. E., and
      Tamura, T. (1999) Biochim. Biophys. Acta 1472, 323-32] is explained by the rapid
      oxidation of (6S)-10-formyltetrahydrofolate (10-HCO-THF), which is produced by in
      vivo chemical processes from the above folates. An oxidation of 10-HCO-THF
      produces 10-formyldihydrofolate (10-HCO-DHF), which no longer has the asymmetric
      center at carbon-6 and is metabolized by aminoimidazole carboxamide ribotide
      (AICAR) transformylase forming bioactive dihydrofolate. Since cytochrome c
      (Fe(3+)) rapidly oxidizes both (6R)- and (6S)-10-HCO-THF [Baggott et al. (2001)
      Biochem. J. 354, 115-22], we investigated the metabolism of 10-HCO-THF by
      isolated rat liver mitochondria. We found that 10-HCO-THF supported the
      respiration of mitochondria without uncoupling ATP synthesis. The site of
      electron donation was identified as complex IV, which contains cytochrome c; the
      folate product was 10-HCO-DHF, and the reaction was saturable with respect to 10
      HCO-THF. Both (6S)- (unnatural) and (6R)-10-HCO-THF supported the respiration of
      mitochondria, whereas (6S)-5-formyltetrahydrofolate (5-HCO-THF) was inactive. To
      our knowledge, this cytochrome c oxidation of 10-HCO-THF to 10-HCO-DHF in the
      mitochondrial intermembrane space represents a possible folate metabolic pathway
      previously unidentified and would explain the bioactivity of unnatural carbon-6
      isomers, (6R)-5-HCO-THF and (6S)-5,10-CH-THF, in humans.

PMID- 11969425
TI  - Evaluation by mutagenesis of the roles of His309, His315, and His319 in the
      coenzyme site of pig heart NADP-dependent isocitrate dehydrogenase.
AB  - Sequence alignment predicts that His(309) of pig heart NADP-dependent isocitrate
      dehydrogenase is equivalent to His(339) of the Escherichia coli enzyme, which
      interacts with the coenzyme in the crystal structure [Hurley et al. (1991)
      Biochemistry 30, 8671-8688], and porcine His(315) and His(319) are close to that
      site. The mutant porcine enzymes H309Q, H309F, H315Q, and H319Q were prepared by
      site-directed mutagenesis, expressed in E. coli, and purified. The H319Q mutant
      has K(m) values for NADP, isocitrate, and Mn(2+) similar to those of wild-type
      enzyme, and V(max) = 20.1, as compared to 37.8 micromol of NADPH min(-1) (mg of
      protein)(-1) for wild type. Thus, His(319) is not involved in coenzyme binding
      and has a minimal effect on catalysis. In contrast, H315Q exhibits a K(m) for
      NADP 40 times that of wild type and V(max) = 16.2 units/mg of protein, with K(m)
      values for isocitrate and Mn(2+) similar to those of wild type. These results
      implicate His(315) in the region of the NADP site. Replacement of His(309) by Q
      or F yields enzyme with no detectable activity. The His(309) mutants bind NADPH
      poorly, under conditions in which wild type and H319Q bind 1.0 mol of NADPH/mol
      of subunit, indicating that His(309) is important for the binding of coenzyme.
      The His(309) mutants bind isocitrate stoichiometrically, as do wild-type and the
      other mutant enzymes. However, as distinguished from the wild-type enzyme, the
      His(309) mutants are not oxidatively cleaved by metal isocitrate, implying that
      the metal ion is not bound normally. Since circular dichroism spectra are similar
      for wild type, H315Q, and H319Q, these amino acid substitutions do not cause
      major conformational changes. In contrast, replacement of His(309) results in
      detectable change in the enzyme's CD spectrum and therefore in its secondary
      structure. We propose that His(309) plays a significant role in the binding of
      coenzyme, contributes to the proper coordination of divalent metal ion in the
      presence of isocitrate, and maintains the normal conformation of the enzyme.

PMID- 11969427
TI  - Electrostatic effects in highly charged proteins: salt sensitivity of pKa values
      of histidines in staphylococcal nuclease.
AB  - The pK(a) values of most histidines in small peptides and in myoglobin increase
      on average by 0.30 unit between 0.02 and 1.5 M NaCl [Kao et al. (2000) Biophys.
      J. 79, 1637]. The DeltapK(a) values reflect primarily the ionic strength
      dependence of the solvation energy; screening of Coulombic interactions
      contributes only in a minor way. This implies that Coulombic interactions are
      weak, or that attractive and repulsive contributions to the pK(a) values are
      balanced. To distinguish experimentally between these two possibilities, and to
      further characterize the magnitude and salt sensitivity of surface electrostatic
      interactions in proteins, the salt dependence of pK(a) values of histidines in
      staphylococcal nuclease was measured by (1)H NMR spectroscopy. Three of the four
      histidines titrated with significantly depressed pK(a) values, and the salt
      sensitivity of all histidine pK(a) values was substantial. In three cases, the
      pK(a) values increased by a full unit between 0.01 and 1.5 M KCl. Anion-specific
      effects were found; the pK(a) values measured under equivalent ionic strengths in
      SCN(-) and SO(4)(2-) were higher than in Cl(-); the order of the sensitivity of
      pK(a) values to anions was SCN(-) > Cl(-) > SO(4)(2-). Structure-based pK(a)
      calculations with continuum methods were performed to interpret the measured
      effects structurally and to test their ability to capture the experimental
      behavior. Calculations in which the protein interior was treated empirically with
      a dielectric constant of 20 reproduced the pK(a) values and their dependence on
      the concentration of Cl(-). According to the calculations, the pK(a) values are
      depressed because of unfavorable self-energies and repulsive Coulombic
      interactions. Their striking salt sensitivity reflects screening of weak,
      repulsive, Coulombic interactions among charges separated by more than 10 A. Long
      range Coulombic interactions on the surfaces of proteins are weak, but they can
      add up to produce substantial electrostatic effects when positive and negative
      charges are not balanced.

PMID- 11969426
TI  - Effects of amino acid substitutions at beta 131 on the structure and properties
      of hemoglobin: evidence for communication between alpha 1 beta 1- and alpha 1
      beta 2-subunit interfaces.
AB  - Substitutions of Asn, Glu, and Leu for Gln at the beta131 position of the
      hemoglobin molecule result in recombinant hemoglobins (rHbs) with moderately
      lowered oxygen affinity and high cooperativity compared to human normal adult
      hemoglobin (Hb A). The mutation site affects the hydrogen bonds present at the
      alpha(1)beta(1)-subunit interface between alpha103His and beta131Gln as well as
      that between alpha122His and beta35Tyr. NMR spectroscopy shows that the hydrogen
      bonds are indeed perturbed; in the case of rHb (beta131Gln --> Asn) and rHb
      (beta131Gln --> Leu), the perturbations are propagated to the other
      alpha(1)beta(1)-interface H-bond involving alpha122His and beta35Tyr. Proton
      exchange measurements also detect faster exchange rates for both alpha(1)beta(1)
      interface histidine side chains of the mutant rHbs in 0.1 M sodium phosphate
      buffer at pH 7.0 than for those of Hb A under the same conditions. In addition,
      the same measurements in 0.1 M Tris buffer at pH 7.0 show a much slower exchange
      rate for mutant rHbs and Hb A. One of the mutants, rHb (beta131Gln --> Asn),
      shows the conformational exchange of its interface histidines, and exchange rate
      measurements have been attempted. We have also conducted studies on the
      reactivity of the SH group of beta93Cys (a residue located in the region of the
      alpha(1)beta(2)-subunit interface) toward p-mercuribenzoate, and our results show
      that low-oxygen-affinity rHbs have a more reactive beta93Cys than Hb A in the CO
      form. Our results indicate that there is communication between the
      alpha(1)beta(1)- and alpha(1)beta(2)-subunit interfaces, and a possible
      communication pathway for the cooperative oxygenation of Hb A that allows the
      alpha(1)beta(1)-subunit interface to modulate the functional properties in
      conjunction with the alpha(1)beta(2) interface is proposed.

PMID- 11969428
TI  - Resonance Raman spectroscopy and quantum chemical calculations reveal structural
      changes in the active site of photoactive yellow protein.
AB  - Photoactive yellow protein (PYP) is a bacterial photoreceptor containing a 4
      hydroxycinnamyl chromophore. Photoexcitation of PYP triggers a photocycle that
      involves at least two intermediate states: an early red-shifted PYP(L)
      intermediate and a long-lived blue-shifted PYP(M) intermediate. In this study, we
      have explored the active site structures of these intermediates by resonance
      Raman spectroscopy. Quantum chemical calculations based on a density functional
      theory are also performed to simulate the observed spectra. The obtained
      structure of the chromophore in PYP(L) has cis configuration and no hydrogen bond
      at the carbonyl oxygen. In PYP(M), the cis chromophore is protonated at the
      phenolic oxygen and forms the hydrogen bond at the carbonyl group. These results
      allow us to propose structural changes of the chromophore during the photocycle
      of PYP. The chromophore photoisomerizes from trans to cis configuration by
      flipping the carbonyl group to form PYP(L) with minimal perturbation of the
      tightly packed protein interior. Subsequent conversion to PYP(M) involves
      protonation on the phenolic oxygen, followed by rotation of the chromophore as a
      whole. This large motion of the chromophore is potentially correlated with the
      succeeding global conformational changes in the protein, which ultimately leads
      to transduction of a biological signal.

PMID- 11969431
TI  - Correct microcanonical ensemble in molecular dynamics.
AB  - The statistical-mechanics ensemble corresponding to equilibrium molecular
      dynamics simulations is different than the usual microcanonical EVN ensemble.
      Historically molecular dynamics has been associated with the EVNM ensemble, where
      M is the constant total linear momentum of the system. We show that the correct
      ensemble associated with molecular dynamics is the EVNMG ensemble where G is the
      constant of the motion associated with Galilean boosts. The ensemble associated
      with molecular dynamics simulations has, apparently, not been previously
      recognized. An earlier problem with the pressure in the new ensemble disappears.

PMID- 11969429
TI  - Phosphatidylserine binding alters the conformation and specifically enhances the
      cofactor activity of bovine factor Va.
AB  - Factor V(a) is a cofactor for the serine protease factor X(a) that activates
      prothrombin to thrombin in the presence of Ca(2+) and a platelet membrane
      surface. A platelet membrane lipid, phosphatidylserine (PS), regulates the
      proteolytic activity of factor X(a) as well as the structure of prothrombin. Here
      we ask whether PS also regulates the structure and cofactor activity of factor
      V(a), which is a heterodimer composed of one heavy chain (A1-A2 domains) and one
      light chain (A3-C1-C2 domains). We use fluorescence, circular dichroism,
      equilibrium dialysis, and activity measurements to demonstrate the following: (1)
      Factor V(a) has four sites for dicaproyl-sn-glycero-3-phospho-L-serine (C(6)PS, a
      soluble form of PS); the heavy and light chains each bind two C(6)PS molecules.
      (2) In the absence of Ca(2+), only two sites remain, one in the heavy chain and
      another in the light chain. (3) Binding to these sites causes conformational
      changes evidenced by changes in intrinsic fluorescence and in CD spectra and
      changes in cofactor activity. (4) At least some of the four lipid binding sites
      are nonspecific with respect to soluble lipid species, but the site(s) that
      regulate(s) cofactor activity is (are) specific for C(6)PS, phosphatidic acid, or
      phosphatidyl(homo)serine and produce a response comparable to that seen with a PS
      containing membrane. (5) Like Ca(2+), C(6)PS also mediates the interaction
      between factor V(a) heavy (V(a)-HC) and light (V(a)-LC) chains. We conclude that
      PS regulates both the cofactor and the enzyme of the prothrombin-activating
      complex.

PMID- 11969430
TI  - Enzymatic assembly of epothilones: the EpoC subunit and reconstitution of the
      EpoA-ACP/B/C polyketide and nonribosomal peptide interfaces.
AB  - The biosynthesis of epothilones, a family of hybrid polyketide (PK)/nonribosomal
      peptide (NRP) antitumor agents, provides an ideal system to study a hybrid PK/NRP
      natural product with significant biomedical value. Here the third enzyme involved
      in epothilone production, the five domain 195 kDa polyketide synthase (PKS) EpoC
      protein, has been expressed and purified from Escherichia coli. EpoC was combined
      with the first two enzymes of the epothilone biosynthesis pathway, the acyl
      carrier protein (ACP) domain of EpoA and EpoB, to reconstitute the early steps in
      epothilone biosynthesis. The acyltransferase (AT) domain of EpoC transfers the
      methylmalonyl moiety from methylmalonyl-CoA to the holo HS-acyl carrier protein
      (ACP) in an autoacylation reaction. The ketosynthase (KS) domain of EpoC
      decarboxylates the methylmalonyl-S-EpoC acyl enzyme to generate the carbon
      nucleophile that reacts with methylthiazolylcarboxyl-S-EpoB. The resulting
      condensation product can be reduced in the presence of NADPH by the ketoreductase
      (KR) domain of EpoC and then dehydrated by the dehydratase (DH) domain to produce
      the methylthiazolylmethylacrylyl-S-EpoC acyl enzyme intermediate that serves as
      the acyl donor for subsequent elongation of the epothilone chain. The acetyl-CoA
      donor can be replaced with propionyl-CoA, isobutyryl-CoA, and benzoyl-CoA and the
      acyl chains accepted by both EpoB and EpoC subunits to produce ethyl-, isopropyl
      , and phenylthiazolylmethylacrylyl-S-EpoC acyl enzyme intermediates, suggesting
      that future combinatorial biosynthetic variations in epothilone assembly may be
      feasible. These results demonstrate in vitro reconstitution of both the PKS/NRPS
      interface (EpoA-ACP/B) and the NRPS/PKS interface (EpoB/C) in the assembly line
      for this antitumor natural product.

PMID- 11969432
TI  - Effect of angular momentum conservation in the phase transitions of collapsing
      systems.
AB  - The effect of angular momentum conservation within microcanonical thermodynamics
      is considered. This is relevant in self-gravitating systems, where angular
      momentum is conserved and the collapsing nature of the forces makes the
      microcanonical ensemble the proper statistical description of the physical
      processes. The microcanonical distribution function with nonvanishing angular
      momentum is obtained as a function of the coordinates of the particles. As an
      example, a simple model, introduced by Thirring long ago [Z. Phys. 235, 339
      (1970)], is worked out. The phase diagram contains three phases: For low values
      of the angular momentum L the system behaves as the original model, showing a
      complete collapse at low energies and a convex intruder in the entropy. For
      intermediate values of L the collapse at low energies is not complete, and the
      entropy still has a convex intruder. For large L there is neither collapse nor
      anomalies in the thermodynamical quantities. A short discussion of the extension
      of these results to more realistic situations is given.

PMID- 11969433
TI  - Random walkers in one-dimensional random environments: exact renormalization
      group analysis.
AB  - Sinai's model of diffusion in one dimension with random local bias is studied by
      a real space renormalization group, which yields exact results at long times. The
      effects of an additional small uniform bias force are also studied. We obtain
      analytically the scaling form of the distribution of the position x(t) of a
      particle, the probability of it not returning to the origin, and the
      distributions of first passage times, in an infinite sample as well as in the
      presence of a boundary and in a finite but large sample. We compute the
      distribution of the meeting time of two particles in the same environment. We
      also obtain a detailed analytic description of the thermally averaged
      trajectories by computing quantities such as the joint distribution of the number
      of returns and of the number of jumps forward. These quantities obey multifractal
      scaling, characterized by generalized persistence exponents theta(g) which we
      compute. In the presence of a small bias, the number of returns to the origin
      becomes finite, characterized by a universal scaling function which we obtain.
      The full statistics of the distribution of successive times of return of
      thermally averaged trajectories is obtained, as well as detailed analytical
      information about correlations between directions and times of successive jumps.
      The two-time distribution of the positions of a particle, x(t) and x(t') with
      t>t', is also computed exactly. It is found to exhibit "aging" with several time
      regimes characterized by different behaviors. In the unbiased case, for t-t'
      approximately t'alpha with alpha>1, it exhibits a ln t/ln t' scaling, with a
      singularity at coinciding rescaled positions x(t)=x(t'). This singularity is a
      novel feature, and corresponds to particles that remain in a renormalized valley.
      For closer times alpha<1, the two-time diffusion front exhibits a
      quasiequilibrium regime with a ln(t-t')/ln t' behavior which we compute. The
      crossover to a t/t' aging form in the presence of a small bias is also obtained
      analytically. Rare events corresponding to intermittent splitting of the thermal
      packet between separated wells which dominate some averaged observables are also
      characterized in detail. Connections with the Green function of a one-dimensional
      Schrodinger problem and quantum spin chains are discussed.

PMID- 11969434
TI  - Stochastic resonance in threshold systems.
AB  - We consider signal processing in simple threshold systems with nonstationary
      additive and/or multiplicative noise. A discrete-time process with a small
      periodical signal masked by noise represents an input. The systems convert
      sampled input data to a nonstationary random point event flow carrying some
      information on an input signal. As it is shown in our previous study [M.M.
      Alibegov, Astron. Lett. 22, 564 (1996)], the Rayleigh spectral function of a
      random point event train estimates a signal-to-noise ratio (SNR) at selected
      frequencies. Based on these results, we compute a system response at signal
      frequencies as a function of threshold and input noise intensity. The threshold
      systems are shown to reveal stochastic resonance (SR), i.e., output SNR exhibits
      a maximum at resonant noise intensity (intensities) and threshold(s) at rather
      common conditions. We show that SR and Rayleigh spectral technique allow us to
      carry out numerical signal detection in data sets with noise.

PMID- 11969435
TI  - Coefficient scaling.
AB  - We prove a remarkably simple but powerful recursion relation for the coefficients
      of iterated polynomials. We also prove that the recursion relation holds for the
      coefficients of certain functions of the iterated polynomial. Using the recursion
      relations, we obtain a closed-form expression for the average number of closed
      loop self-avoiding walks per site on a family of fractal lattices. We describe
      numerical results, which exhibit log-periodic oscillations, and find good
      agreement between these results and the theory developed here, which predicts the
      existence of the log-periodic oscillations and their amplitudes. Finally, we
      discuss insights gained into the mathematical origins of critical phenomena.

PMID- 11969436
TI  - Jamming transition in a two-dimensional traffic flow model.
AB  - Phase transition and critical phenomenon are investigated in the two-dimensional
      traffic flow numerically and analytically. The one-dimensional lattice
      hydrodynamic model of traffic is extended to the two-dimensional traffic flow in
      which there are two types of cars (northbound and eastbound cars). It is shown
      that the phase transition among the freely moving phase, the coexisting phase,
      and the uniformly congested phase occurs below the critical point. Above the
      critical point, no phase transition occurs. The value a(c) of the critical point
      decreases as increasing fraction c of the eastbound cars for c<or=0.5. The linear
      stability theory is applied. The neutral stability lines are found. The time
      dependent Ginzburg-Landau (TDGL) equation is derived by the use of nonlinear
      analysis. The phase separation lines, the spinodal lines, and the critical point
      are calculated from the TDGL equation.

PMID- 11969437
TI  - Unified view of scaling laws for river networks.
AB  - Scaling laws that describe the structure of river networks are shown to follow
      from three simple assumptions. These assumptions are (1) river networks are
      structurally self-similar, (2) single channels are self-affine, and (3) overland
      flow into channels occurs over a characteristic distance (drainage density is
      uniform). We obtain a complete set of scaling relations connecting the exponents
      of these scaling laws and find that only two of these exponents are independent.
      We further demonstrate that the two predominant descriptions of network structure
      (Tokunaga's law and Horton's laws) are equivalent in the case of landscapes with
      uniform drainage density. The results are tested with data from both real
      landscapes and a special class of random networks.

PMID- 11969438
TI  - Deterministic transport in ratchets.
AB  - We present the deterministic transport properties of driven overdamped particles
      in a simple piecewise-linear ratchet potential. We consider the effects on the
      stationary current due to local spatial asymmetry, time asymmetry in the driving
      force, and we include the possibility of a global spatial asymmetry. We present
      an extremely simple scheme for evaluating the current that is established on the
      ratchet within an "adiabatic" approximation, and compare the results with exact
      numerical integration of the process.

PMID- 11969439
TI  - Adding and multiplying random matrices: a generalization of Voiculescu's
      formulas.
AB  - In this paper, we give an elementary proof of the additivity of the functional
      inverses of the resolvents of large N random matrices, using recently developed
      matrix model techniques. This proof also gives a very natural generalization of
      these formulas to the case of measures with an external field. A similar approach
      yields a relation of the same type for multiplication of random matrices.

PMID- 11969440
TI  - Variational principle for limit cycles of the Rayleigh-van der Pol equation.
AB  - We show that the amplitude of the limit cycle of Rayleigh's equation can be
      obtained from a variational principle. We use this principle to reobtain the
      asymptotic values for the period and amplitude of the Rayleigh and van der Pol
      equations. Limit cycles of general Lienard systems can also be derived from a
      variational principle.

PMID- 11969441
TI  - Reversing the perturbation in nonequilibrium molecular dynamics: an easy way to
      calculate the shear viscosity of fluids.
AB  - A nonequilibrium method for calculating the shear viscosity is presented. It
      reverses the cause-and-effect picture customarily used in nonequilibrium
      molecular dynamics: the effect, the momentum flux or stress, is imposed, whereas
      the cause, the velocity gradient or shear rate, is obtained from the simulation.
      It differs from other Norton-ensemble methods by the way in which the steady
      state momentum flux is maintained. This method involves a simple exchange of
      particle momenta, which is easy to implement. Moreover, it can be made to
      conserve the total energy as well as the total linear momentum, so no coupling to
      an external temperature bath is needed. The resulting raw data, the velocity
      profile, is a robust and rapidly converging property. The method is tested on the
      Lennard-Jones fluid near its triple point. It yields a viscosity of 3.2-3.3, in
      Lennard-Jones reduced units, in agreement with literature results.

PMID- 11969442
TI  - Exact stationary state for an asymmetric exclusion process with fully parallel
      dynamics.
AB  - The exact stationary state of an asymmetric exclusion process with fully parallel
      dynamics is obtained using the matrix product ansatz. We give a simple derivation
      for the deterministic case by a physical interpretation of the dimension of the
      matrices. We prove the stationarity via a cancellation mechanism, and by making
      use of an explicit representation of the matrix algebra we easily find closed
      expressions for the correlation functions in the general probabilistic case.
      Asymptotic expressions, obtained by making use of earlier results, allow us to
      derive the exact phase diagram.

PMID- 11969443
TI  - Transport in the XX chain at zero temperature: emergence of flat magnetization
      profiles.
AB  - We study the connection between magnetization transport and magnetization
      profiles in zero-temperature XX chains. The time evolution of the transverse
      magnetization m(x,t) is calculated using an inhomogeneous initial state that is
      the ground state at fixed magnetization but with m reversed from -m(0) for x<0 to
      m(0) for x>0. In the long-time limit, the magnetization evolves into a scaling
      form m(x,t)=Phi(x/t) and the profile develops a flat part (m=Phi=0) in the
      (x/t)<or=c(m(0)) region. The flat region shrinks to zero if m(0)-->1/2 while it
      expands with the maximum velocity c(0)=1 for m(0)-->0. The states emerging in the
      scaling limit are compared to those of a homogeneous system where the same
      magnetization current is driven by a bulk field, and we find that the expectation
      values of various quantities (energy, occupation number in the fermionic
      representation) agree in the two systems.

PMID- 11969444
TI  - Critical exponents for diluted resistor networks.
AB  - An approach by Stephen [Phys. Rev. B 17, 4444 (1978)] is used to investigate the
      critical properties of randomly diluted resistor networks near the percolation
      threshold by means of renormalized field theory. We reformulate an existing field
      theory by Harris and Lubensky [Phys. Rev. B 35, 6964 (1987)]. By a decomposition
      of the principal Feynman diagrams, we obtain diagrams which again can be
      interpreted as resistor networks. This interpretation provides for an alternative
      way of evaluating the Feynman diagrams for random resistor networks. We calculate
      the resistance crossover exponent phi up to second order in epsilon=6-d, where d
      is the spatial dimension. Our result phi=1+epsilon/42+4epsilon(2)/3087 verifies a
      previous calculation by Lubensky and Wang, which itself was based on the Potts
      model formulation of the random resistor network.

PMID- 11969445
TI  - Generalized quantum Langevin equations from the forward-backward path integral.
AB  - Kleinert and Shabanov [H. Kleinert and S. V. Shabanov, Phys. Lett. A 200, 224
      (1995)] have derived the quantum Langevin equations from the Feynman-Vernon
      forward-backward path integral for a density matrix of a quantum system in a
      thermal oscillator bath. However, their derivation is confined to an Ohmic case.
      In this paper we derive the generalized quantum Langevin equations from the
      forward-backward path integral, by extending the Kleinert-Shabanov method to a
      general case.

PMID- 11969446
TI  - Cluster-approximation mean-field theory of a class of cellular automaton models.
AB  - A cluster-approximation mean-field scheme, which may be used to describe some
      cellular automaton (CA) models, is introduced based on analyzing the evolution of
      cluster states. In this scheme the description of microscopic processes is exact
      within a cluster, and approximate for the interaction between clusters and the
      environment. The approach to building the theory is illustrated by a surface
      reaction-like CA model very similar to the model of Ziff, Gulari, and Barshad. A
      set of equations of motion concerning the evolution of microscopic cluster states
      is derived, and some results from these equations are given.

PMID- 11969447
TI  - Stochastic multiplicative processes with reset events.
AB  - We study a stochastic multiplicative process with reset events. It is shown that
      the model develops a stationary power-law probability distribution for the
      relevant variable, whose exponent depends on the model parameters. Two
      qualitatively different regimes are observed, corresponding to intermittent and
      regular behavior. In the boundary between them, the mean value of the relevant
      variable is time independent, and the exponent of the stationary distribution
      equals -2. The addition of diffusion to the system modifies in a nontrivial way
      the profile of the stationary distribution. Numerical and analytical results are
      presented.

PMID- 11969448
TI  - Dynamic behavior of driven interfaces in models with two absorbing states.
AB  - We study the dynamics of an interface (active domain) between different absorbing
      regions in models with two absorbing states in one dimension: probabilistic
      cellular automata models and interacting monomer-dimer models. These models
      exhibit a continuous transition from an active phase into an absorbing phase,
      which belongs to the directed Ising (DI) universality class. In the active phase,
      the interface spreads ballistically into the absorbing regions and the interface
      width diverges linearly in time. Approaching the critical point, the spreading
      velocity of the interface vanishes algebraically with a DI critical exponent.
      Introducing a symmetry-breaking field h that prefers one absorbing state over the
      other drives the interface to move asymmetrically toward the unpreferred
      absorbing region. In Monte Carlo simulations, we find that the spreading velocity
      of this driven interface shows a discontinuous jump at criticality. We explain
      that this unusual behavior is due to a finite relaxation time in the absorbing
      phase. The crossover behavior from the symmetric case (DI class) to the
      asymmetric case (directed percolation class) is also studied. We find the scaling
      dimension of the symmetry-breaking field y(h)=1.21(5).

PMID- 11969449
TI  - Chord-distribution functions of three-dimensional random media: approximate first
      passage times of Gaussian processes.
AB  - The main result of this paper is a semianalytic approximation for the chord
      distribution functions of three-dimensional models of microstructure derived from
      Gaussian random fields. In the simplest case the chord functions are equivalent
      to a standard first-passage time problem, i.e., the probability density governing
      the time taken by a Gaussian random process to first exceed a threshold. We
      obtain an approximation based on the assumption that successive chords are
      independent. The result is a generalization of the independent interval
      approximation recently used to determine the exponent of persistence time decay
      in coarsening. The approximation is easily extended to more general models based
      on the intersection and union sets of models generated from the isosurfaces of
      random fields. The chord-distribution functions play an important role in the
      characterization of random composite and porous materials. Our results are
      compared with experimental data obtained from a three-dimensional image of a
      porous Fontainebleau sandstone and a two-dimensional image of a tungsten-silver
      composite alloy.

PMID- 11969450
TI  - Robustness of scale invariance in models with self-organized criticality.
AB  - A random-neighbor extremal stick-slip model is introduced. In the thermodynamic
      limit, the distribution of states has a simple analytical form and the mean
      avalanche size, as a function of the coupling parameter, is exactly calculable.
      The system is critical only at a special point J(c) in coupling parameter space.
      However, the critical region around this point, where approximate scale
      invariance holds, is very large, suggesting a mechanism for explaining the
      ubiquity of power laws in nature.

PMID- 11969451
TI  - Noise stabilization of self-organized memories.
AB  - We investigate a nonlinear dynamical system which "remembers" preselected values
      of a system parameter. The deterministic version of the system can encode many
      parameter values during a transient period, but in the limit of long times,
      almost all of them are forgotten. Here we show that a certain type of stochastic
      noise can stabilize multiple memories, enabling many parameter values to be
      encoded permanently. We present analytic results that provide insight both into
      the memory formation and into the noise-induced memory stabilization. The
      relevance of our results to experiments on the charge-density wave material NbSe3
      is discussed.

PMID- 11969452
TI  - Superadditive correlation.
AB  - The fact that correlation does not imply causation is well known. Correlation
      between variables at two sites does not imply that the two sites directly
      interact, because, e.g., correlation between distant sites may be induced by
      chaining of correlation between a set of intervening, directly interacting sites.
      Such "noncausal correlation" is well understood in statistical physics: an
      example is long-range order in spin systems, where spins which have only short
      range direct interactions, e.g., the Ising model, display correlation at a
      distance. It is less well recognized that such long-range "noncausal"
      correlations can in fact be stronger than the magnitude of any causal correlation
      induced by direct interactions. We call this phenomenon superadditive correlation
      (SAC). We demonstrate this counterintuitive phenomenon by explicit examples in
      (i) a model spin system and (ii) a model continuous variable system, where both
      models are such that two variables have multiple intervening pathways of indirect
      interaction. We apply the technique known as decimation to explain SAC as an
      additive, constructive interference phenomenon between the multiple pathways of
      indirect interaction. We also explain the effect using a definition of the
      collective mode describing the intervening spin variables. Finally, we show that
      the SAC effect is mirrored in information theory, and is true for mutual
      information measures in addition to correlation measures. Generic complex systems
      typically exhibit multiple pathways of indirect interaction, making SAC a
      potentially widespread phenomenon. This affects, e.g., attempts to deduce
      interactions by examination of correlations, as well as, e.g., hierarchical
      approximation methods for multivariate probability distributions, which introduce
      parameters based on successive orders of correlation.

PMID- 11969453
TI  - Monte Carlo simulation of an antiferromagnetic Ising model at two competing
      temperatures.
AB  - We consider a two-dimensional antiferromagnet Ising system interacting with a
      heat bath at temperature T. The dynamics of the system is simulated by two
      competing stochastic processes: the two-spin-exchange Kawasaki kinetics at
      temperature T>0 and the one-spin-flip Glauber dynamics at T(G)-->0(-), which
      mimics the increase of the energy of the system. These two processes have
      probabilities 1-p and p, respectively. Monte Carlo simulations were employed to
      determine the phase diagram for the stationary states of the model and the
      corresponding critical exponents. Contrary to the ferromagnetic case, the phase
      diagram obtained does not exhibit the phenomenon of self-organization: for any
      nonzero value of the competing parameter p, and for any value of T, the only
      stationary phase which remains is the ferromagnetic one. At the phase transition
      between the antiferromagnetic and paramagnetic phases, at p=0, the values found
      for the critical exponents agree with those of the corresponding equilibrium
      Ising model.

PMID- 11969454
TI  - Critical properties of the three-dimensional equivalent-neighbor model and
      crossover scaling in finite systems.
AB  - Accurate numerical results are presented for the three-dimensional equivalent
      neighbor model on a cubic lattice, for 12 different interaction ranges
      (coordination number between 18 and 250). These results allow the determination
      of the range dependences of the critical temperature and various critical
      amplitudes, which are compared to renormalization-group predictions. In addition,
      the analysis yields an estimate for the interaction range at which the leading
      corrections to scaling vanish for the spin-1 / 2 model, and confirms earlier
      conclusions that the leading Wegner correction must be negative for the three
      dimensional (nearest-neighbor) Ising model. By complementing these results with
      Monte Carlo data for systems with coordination numbers as large as 52 514, the
      full finite-size crossover curves between classical and Ising-like behavior are
      obtained as a function of a generalized Ginzburg parameter. Also, the crossover
      function for the effective magnetic exponent is determined.

PMID- 11969455
TI  - Cyclostationarity and stochastic resonance in threshold devices.
AB  - This paper intends to show how the theory of stochastic cyclostationary processes
      can be used to study stochastic resonance in static nonlinearities. The statistic
      we use is the covariance function of the output. The covariance is a second-order
      cumulant and is not dependent on by the mean. Furthermore, this covariance is not
      averaged in time as is usually done in the stochastic resonance literature. A two
      dimensional Fourier transform of the covariance gives the so-called spectral
      correlation. The spectral correlation depends on the usual harmonic frequency and
      on another frequency, called cycle frequency. The cyclostationarity of a signal
      makes the spectral correlation discrete in the cycle frequency. The zero cycle
      frequency corresponds to the usual "stationary power spectrum" used in the
      stochastic resonance literature. We thus exploit all the second-order statistical
      information. We first revisit classical stochastic resonance in threshold devices
      using the spectral correlation, showing that the effect is seen for nonzero cycle
      frequencies. The cases of additive and multiplicative noise are detailed. We then
      study stochastic resonance in threshold devices for communication signals. These
      signals are usually modeled as stochastic cyclostationary processes. We show that
      stochastic resonance occurs, and the phenomenon is quantified using the spectral
      correlation of the output: The amplitude of the spectral correlation at nonzero
      cycle frequencies presents a maximum as the power of the input noise is
      increased.

PMID- 11969456
TI  - Trapping reactions for mobile particles and a trap in the laboratory frame.
AB  - We have used a stochastic model to obtain the exact spatial particle density
      profile for the trapping process A+B-->B in a one-dimensional lattice with a
      single trap, as seen from the laboratory frame. We obtain the profile for either
      perfect or imperfect reactions when A particles are immobile, but only for
      perfect absorption in the general case where both particles are mobile with
      different diffusivities. This profile is found to be similar to that seen from
      the reference system attached to the trap, the most noticeable difference being
      near the origin.

PMID- 11969457
TI  - Multidimensional advection and fractional dispersion.
AB  - Extension of the fractional diffusion equation to two or three dimensions is not
      as simple as extension of the second-order equation. This is revealed by the
      solutions of the equations: unlike the Gaussian, the most general stable vector
      cannot be generated with an atomistic measure on the coordinate axes. A random
      combination of maximally skewed stable variables on the unit sphere generates a
      stable vector that is a general model of a diffusing particle. Subsets are
      symmetric stable vectors that have previously appeared in the literature and the
      well-known multidimensional Brownian motion. A multidimensional fractional
      differential operator is defined in the process.

PMID- 11969458
TI  - Temperature dependence of facet ridges in crystal surfaces.
AB  - The equilibrium crystal shape of a body-centered solid-on-solid (BCSOS) model on
      a honeycomb lattice is studied numerically. We focus on the facet ridge end
      points (FRE's). These points are equivalent to one-dimensional Kardar-Parisi
      Zhang-type growth in the exactly soluble square lattice BCSOS model. In our more
      general context the transfer matrix is not stochastic at the FRE points, and a
      more complex structure develops. We observe ridge lines sticking into the rough
      phase where the surface orientation jumps inside the rounded part of the crystal.
      Moreover, the rough-to-faceted edges become first order with a jump in surface
      orientation, between the FRE point and Pokrovsky-Talapov (PT) type critical
      endpoints. The latter display anisotropic scaling with exponent z=3 instead of
      familiar PT value z=2.

PMID- 11969459
TI  - Wave front for a reaction-diffusion system and relativistic Hamilton-Jacobi
      dynamics.
AB  - The problem of wave-front propagation for the n-dimensional reaction-diffusion
      system involving Kolmogorov-Petrovskii-Piskunov kinetics and the diffusion
      transport with a finite velocity has been considered. By using a scaling
      procedure we have given an asymptotic derivation of the equation governing the
      evolution of a reaction front in the long-time large-distance limit. It has been
      found that this equation is identical in form to the relativistic Hamilton-Jacobi
      equation. In the case of a constant value of chemical rate function we have
      derived exact formulas for the position of reaction front and the speed of
      propagation by using relativistic mechanics techniques.

PMID- 11969460
TI  - Mechanical and Langevin thermostats: Gulton staircase problem.
AB  - Dynamics in a Gulton staircase is considered based on a model in which many
      particles, coupled through an average velocity, are in contact with a Gaussian
      thermostat. Computer simulation gives information on entropy production, the
      stationary mass current, and distribution functions of both particle positions
      and momenta. A Langevin thermostat is also considered for the sake of comparison
      with a mechanical thermostat.

PMID- 11969461
TI  - Avalanches in breakdown and fracture processes.
AB  - We investigate the breakdown of disordered networks under the action of an
      increasing external-mechanical or electrical-force. We perform a mean-field
      analysis and estimate scaling exponents for the approach to the instability. By
      simulating two-dimensional models of electric breakdown and fracture we observe
      that the breakdown is preceded by avalanche events. The avalanches can be
      described by scaling laws, and the estimated values of the exponents are
      consistent with those found in mean-field theory. The breakdown point is
      characterized by a discontinuity in the macroscopic properties of the material,
      such as conductivity or elasticity, indicative of a first-order transition. The
      scaling laws suggest an analogy with the behavior expected in spinodal
      nucleation.

PMID- 11969462
TI  - Emergence of order in textured patterns.
AB  - A characterization of textured patterns, referred to as the disorder function
      delta(beta), is used to study properties of patterns generated in the Swift
      Hohenberg equation (SHE). It is shown to be an intensive, configuration
      independent measure. The evolution of random initial states under the SHE
      exhibits two stages of relaxation. The initial phase, where local striped domains
      emerge from a noisy background, is quantified by a power-law decay delta(beta)
      approximately t-(1/2)beta. Beyond a sharp transition, a slower power-law decay of
      delta(beta), which corresponds to the coarsening of striped domains, is observed.
      The transition between the phases advances as the system is driven further from
      the onset of patterns, and suitable scaling of time and delta(beta) leads to the
      collapse of distinct curves. The decay of delta(beta) during the initial phase
      remains unchanged when nonvariational terms are added to the underlying
      equations, suggesting the possibility of observing it in experimental systems. In
      contrast, the rate of relaxation during domain coarsening increases with the
      coefficient of the nonvariational term.

PMID- 11969463
TI  - Canonical phase-space approach to the noisy Burgers equation: probability
      distributions.
AB  - We present a canonical phase-space approach to stochastic systems described by
      Langevin equations driven by white noise. Mapping the associated Fokker-Planck
      equation to a Hamilton-Jacobi equation in the nonperturbative weak noise limit we
      invoke a principle of least action for the determination of the probability
      distributions. We apply the scheme to the noisy Burgers and Kardar-Parisi-Zhang
      equations and discuss the time-dependent and stationary probability
      distributions. In one dimension we derive the long-time skew distribution
      approaching the symmetric stationary Gaussian distribution. In the short-time
      region we discuss heuristically the nonlinear soliton contributions and derive an
      expression for the distribution in accordance with the directed polymer-replica
      and asymmetric exclusion model results. We also comment on the distribution in
      higher dimensions.

PMID- 11969464
TI  - Critical adsorption on curved objects.
AB  - A systematic field-theoretical description of critical adsorption on curved
      objects such as spherical or rodlike colloidal particles immersed in a fluid near
      criticality is presented. The temperature dependence of the corresponding order
      parameter profiles and of the excess adsorption are calculated explicitly.
      Critical adsorption on elongated rods is substantially more pronounced than on
      spherical particles. It turns out that, within the context of critical phenomena
      in confined geometries, critical adsorption on a microscopically thin "needle"
      represents a distinct universality class of its own. Under favorable conditions
      the results are relevant for the flocculation of colloidal particles.

PMID- 11969465
TI  - Dynamic states of a continuum traffic equation with on-ramp.
AB  - We study the phase diagram of the continuum traffic flow model of a highway with
      an on-ramp. Using an open boundary condition, traffic states and metastabilities
      are investigated numerically for several representative values of the upstream
      boundary flux f(up) and for the whole range of the on-ramp flux f(rmp). An
      inhomogeneous but time-independent traffic state (standing localized cluster
      state) is found and related to a recently measured traffic state. Due to the
      density gradient near the on-ramp, a traffic jam can occur even when the
      downstream density is below the critical density of the usual traffic jam
      formation in homogeneous highways, and its structure varies qualitatively with
      f(rmp). The free flow, the recurring hump (RH) state, and the traffic jam can all
      coexist in a certain metastable region where the free flow can undergo phase
      transitions either to the RH state or to the traffic jam state. We also find two
      nontrivial analytic solutions. These solutions correspond to the standing
      localized cluster state and the homogeneous congested traffic state (one form of
      the traffic jam), which are observed in numerical simulations.

PMID- 11969466
TI  - Up and down cascade in a dynamo model: spontaneous symmetry breaking.
AB  - A multiscale turbulent model of dynamo is proposed. A secondary magnetic field is
      generated from a primary field by a flow made of turbulent helical vortices
      (cyclones) of different ranges, and amplified by an up and down cascade
      mechanism. The model displays symmetry breakings of different ranges although the
      system construction is completely symmetric. Large-scale symmetry breakings for
      symmetric conditions of the system evolution are investigated for all kinds of
      cascades: pure direct cascade, pure inverse cascade, and up and down cascade. It
      is shown that long lived symmetry breakings of high scales can be obtained only
      in the case of the up and down cascade. The symmetry breakings find expression in
      intervals of constant polarity of the secondary field (called chrons of the
      geomagnetic field). Long intervals of constant polarity with quick reversals are
      obtained in the model; conditions for such a behavior are investigated. Strong
      variations of the generated magnetic field during intervals of constant polarity
      are also observed in the model. Possible applications of the model to geodynamo
      modeling and various directions of future investigation are briefly discussed.

PMID- 11969467
TI  - Analytical approach to time lag in binary nucleation.
AB  - We present an analytical formula for the time required to establish steady state
      in a nucleating binary system. To test our solution, we evaluate the time lag for
      a range of activities of both components at the vapor-liquid transition, and show
      that our result is in much better agreement with a purely numerical simulation
      than other available analytical formulas, which overestimate the time lag by
      factors of from 2 to 200.

PMID- 11969468
TI  - Onsager-Casimir reciprocity relation for the gyrothermal effect with polyatomic
      gases.
AB  - On the basis of the linearized Boltzmann equation and the boundary condition for
      the distribution function, the Onsager-Casimir reciprocity relation is derived
      for polyatomic gases confined between two cylinders in the presence of a magnetic
      field. The cross effect, namely, the heat flux caused by the rotation of the
      inner cylinder is predicted. Because of the heat flux the cylinder can be heated
      or cooled depending on the direction of the magnetic field. This effect is
      coupled with the gyrothermal effect by the reciprocity relation.

PMID- 11969469
TI  - Kinetic roughening in electrodissolution of copper.
AB  - We studied kinetic roughening of copper surfaces electrochemically dissolved at
      constant current densities by atomic force microscopy. The surface was found to
      roughen with time and the surface width increased with the length scale with the
      roughness exponent alpha of 0.73+/-0.05 in the stationary state. This value is
      different from that in electrochemical deposition, 0.87, under the stable growth
      condition [A. Iwamoto et al., Phys. Rev. Lett. 72, 4025 (1994)]. The observed
      roughening in the dissolution process is discussed in terms of nonlocal effects.

PMID- 11969470
TI  - Quantum stochastic resonance in symmetric systems.
AB  - We investigate the low-temperature quantum stochastic resonance (QSR) phenomenon
      in a two-level system (TLS) which is coupled to an Ohmic heat bath. In contrast
      to common belief we find that QSR occurs also for symmetric (i.e., unbiased)
      TLS's if the viscous friction parameter alpha exceeds a critical value: We
      demonstrate that with respect to the spectral power amplification measure QSR
      always occurs for alpha>1; in contrast, the output signal-to-noise ratio exhibits
      an amplification only for alpha>3/2.

PMID- 11969471
TI  - Stochastic resonance in extended bistable systems: the role of potential
      symmetry.
AB  - We study the role of potential symmetry in a three-field reaction-diffusion
      system presenting bistability by means of a two-state theory for stochastic
      resonance in general asymmetric systems. By analyzing the influence of different
      parameters in the optimization of the signal-to-noise ratio, we observe that this
      magnitude always increases with the symmetry of the system's potential,
      indicating that it is this feature which governs the optimization of the system's
      response to periodic signals.

PMID- 11969472
TI  - Self-organized growth model for a driven interface in random media.
AB  - We introduce a simple self-organized growth model in the quenched Edwards
      Wilkinson universality class. The roughness and growth exponents are obtained for
      the model as alpha approximately 1.15 and beta approximately 0.89, respectively.
      These values of exponents are in good agreement with previous results obtained
      from numerical integrations or discretized model simulations of the quenched
      Edwards-Wilkinson equation. The velocity of a driven interface is found to be
      independent of the slope of the tilted substrate.

PMID- 11969473
TI  - Steady-state cracks in viscoelastic lattice models.
AB  - We study the steady-state motion of mode III cracks propagating on a lattice
      exhibiting viscoelastic dynamics. The introduction of a Kelvin viscosity eta
      allows for a direct comparison between lattice results and continuum treatments.
      Utilizing both numerical and analytical (Wiener-Hopf) techniques, we explore this
      comparison as a function of the driving displacement Delta and the number of
      transverse rows N. At any N, the continuum theory misses the lattice-trapping
      phenomenon; this is well known, but the introduction of eta introduces some new
      twists. More importantly, for large N even at large Delta, the standard two
      dimensional elastodynamics approach completely misses the eta-dependent velocity
      selection, as this selection disappears completely in the leading order naive
      continuum limit of the lattice problem.

PMID- 11969474
TI  - Problems with the definition of renormalized Hamiltonians for momentum-space
      renormalization transformations.
AB  - For classical lattice systems with finite (Ising) spins, we show that the
      implementation of momentum-space renormalization at the level of Hamiltonians
      runs into the same type of difficulties as found for real-space transformations:
      Renormalized Hamiltonians are ill-defined in certain regions of the phase
      diagram.

PMID- 11969475
TI  - Binary data corruption due to a Brownian agent.
AB  - We introduce a model of binary data corruption induced by a Brownian agent
      (active random walker) on a d-dimensional lattice. A continuum formulation allows
      the exact calculation of several quantities related to the density of corrupted
      bits rho, for example, the mean of rho and the density-density correlation
      function. Excellent agreement is found with the results from numerical
      simulations. We also calculate the probability distribution of rho in d=1, which
      is found to be log normal, indicating that the system is governed by extreme
      fluctuations.

PMID- 11969476
TI  - Ising spin glass with arbitrary spin beyond the mean field theory.
AB  - We consider the Ising spin glass for the arbitrary spin S with the short-ranged
      interaction using the Bethe-Peierls approximation previously formulated by Serva
      and Paladin [Phys. Rev. E. 54, 4637 (1996)] for the same system but limited to
      S=1/2. Results obtained by us for arbitrary S are not a simple generalization of
      those for S=1/2. In this paper we mainly concentrate our studies on the
      calculation of the critical temperature and the linear susceptibility in the
      paramagnetic phase as functions of the dimension of the system and spin number S.
      These dependences are illustrated by corresponding plots.

PMID- 11969477
TI  - Spiral drift and core properties.
AB  - We consider the drift of a stable, nonmeandering rotating spiral wave in a singly
      diffusive FitzHugh-Nagumo medium with generic reaction functions; the drift is
      assumed to be caused by a weak time-independent diffusivity gradient or
      convection term in the fast-variable equation. We address, to first order in the
      perturbation, the standard problem whose statement reads, "Given the unperturbed
      solution, as well as the model's parameters, predict the speed and direction of
      the drift in terms of the strength and direction of the perturbation." Our main
      results are as follows: First, we establish a mathematical equivalence between
      true gradients and convective perturbations; second, a variety of numerical
      examples, taken from computer simulations, are presented as a reference base for
      testing drift theories; and third, we propose a semiempirical solution to the
      drift problem, requiring only two quantities to be measured off the unperturbed
      spiral, namely, its period of rotation and the value of the fast variable at its
      center; good agreement with numerical simulations is found for moderately sparse
      spirals.

PMID- 11969478
TI  - Universal level dynamics of complex systems.
AB  - We study the evolution of the distribution of eigenvalues of a N x N matrix
      subject to a random perturbation drawn from (i) a generalized Gaussian ensemble
      and (ii) a non-Gaussian ensemble with a measure variable under the change of
      basis. It turns out that, in case (i), a redefiniton of the parameter governing
      the evolution leads to a Fokker-Planck equation similar to the one obtained when
      the perturbation is taken from a standard Gaussian ensemble (with invaraiant
      measure). This equivalence can therefore help us to obtain the correlations for
      various physically significant cases modeled by generalized Gaussian ensembles by
      using the already known correlations for standard Gaussian ensembles. For large N
      values, our results for both cases (i) and (ii) are similar to those obtained for
      the Wigner-Dyson gas as well as for the perturbation taken from a standard
      Gaussian ensemble. This seems to suggest the independence of evolution, in the
      thermodynamic limit, from the nature of perturbation involved as well as the
      initial conditions and therefore the universality of dynamics of the eigenvalues
      of complex systems.

PMID- 11969479
TI  - Dynamical delocalization in one-dimensional disordered systems with oscillatory
      perturbation.
AB  - The effect of dynamical perturbation on the quantum localization phenomenon in a
      one-dimensional disordered quantum system (1DDS) is investigated systematically
      by a numerical method. The dynamical perturbation is modeled by an oscillatory
      driving force containing M independent (mutually incommensurate) frequency
      components. For M>or=2 a diffusive behavior emerges and in the presence of the
      finite localization length of the asymptotic wave packet can no longer be
      detected numerically. The diffusive motion obeys a subdiffusion law characterized
      by the exponent alpha as xi(t)(2) proportional t(alpha), where xi(t)(2) is the
      mean square displacement of the wave packet at time t. With an increase in M
      and/or the perturbation strength, the exponent alpha rapidly approaches 1, which
      corresponds to normal diffusion. Moreover, the space-time (x-t) dependence of the
      distribution function P(x,t) is reduced to a scaled form decided by alpha and
      another exponent beta such that P(x,t) approximately exp(
      constx(x/t(alpha/2))(beta)), which contains the two extreme limits, i.e., the
      localization limit (alpha=0, beta=1) and the normal-diffusion limit (alpha=1,
      beta=2) in a unified manner. Some 1DDSs driven by the oscillatory perturbation in
      different ways are examined and compared.

PMID- 11969480
TI  - Traces and determinants of strongly stochastic operators.
AB  - Periodic orbit theory allows calculations of long-time properties of chaotic
      systems from traces, dynamical zeta functions, and spectral determinants of
      deterministic evolution operators, which are in turn evaluated in terms of
      periodic orbits. For the case of stochastic dynamics a direct numerical
      evaluation of the trace of an evolution operator is possible as a
      multidimensional integral. Techniques for evaluating such path integrals are
      discussed. Using as an example the logistic map f(x)=lambdax(1-x) with moderate
      to strong additive Gaussian noise, rapid convergence is demonstrated for all
      values of lambda with strong noise as well as at fixed lambda=5 for all noise
      levels.

PMID- 11969481
TI  - Surrogates for finding unstable periodic orbits in noisy data sets.
AB  - Recently, searches for unstable periodic orbits in biological and medical
      applications have become of interest. The motivations for this research range, in
      order of ascending complexity, from efforts to understand the dynamics of simple
      sensory neurons, through speculations regarding neural coding, to the hopeful
      development of new diagnostic and/or control techniques for cardiac and epileptic
      pathologies. Biological and medical data are, however, noisy and nonstationary.
      Findings of unstable periodic orbits in such data thus require convincing
      assessments of their statistical significance. Such tests are accomplished by
      comparison with surrogate data files designed to test an appropriate null
      hypothesis. In this paper we test surrogates generated by three different
      algorithms against correlated noise as well as stable periodic orbits. One of the
      surrogates is new, and has been specifically designed to preserve the shape of
      the attractor. We discuss the suitability of these surrogates and argue that the
      simple shuffled one correctly tests the appropriate null hypothesis.

PMID- 11969482
TI  - Double autoresonance in two-dimensional dynamical systems.
AB  - The phenomenon of double autoresonance in dynamical systems with two degrees of
      freedom is examined. We analyze the motion of a particle in a two-dimensional
      centrally symmetric potential, subject to a homogeneous quasiperiodic external
      field of elliptical polarization. It is shown that if the particle has a
      sufficiently small initial energy, a double resonance is established when the
      slowly varying driving frequency approaches the linear resonance frequency. As
      the driving frequency is changed further, the double resonance is maintained,
      causing a continuous excitation of the oscillator. When nonlinearity becomes
      significant, the motion transforms into nearly circular oscillations. The
      necessary conditions for the persistence of the autoresonance are studied in
      detail.

PMID- 11969483
TI  - Preference of attractors in noisy multistable systems.
AB  - A model system exhibiting a large number of attractors is investigated under the
      influence of noise. Several methods for discriminating two qualitatively
      different regions of the noise intensity are presented, and the phenomenon of
      noise-induced preference of attractors is reported. Finally, the relevance of our
      findings for detection of multiple stable states of systems occurring in nature
      or in the laboratory is pointed out.

PMID- 11969484
TI  - Universal behavior in the parametric evolution of chaotic saddles.
AB  - Chaotic saddles are nonattracting dynamical invariant sets that physically lead
      to transient chaos. As a system parameter changes, chaotic saddles can evolve via
      an infinite number of homoclinic or heteroclinic tangencies of their stable and
      unstable manifolds. Based on previous numerical evidence and a rigorous analysis
      of a class of representative models, we show that dynamical invariants such as
      the topological entropy and the fractal dimension of chaotic saddles obey a
      universal behavior: they exhibit a devil-staircase characteristic as a function
      of the system parameter.

PMID- 11969485
TI  - Stabilization of unstable steady states and periodic orbits in an electrochemical
      system using delayed-feedback control.
AB  - We report numerical and experimental results indicating successful stabilization
      of unstable steady states and periodic orbits in an electrochemical system.
      Applying a continuous delayed-feedback technique not only periodic and chaotic
      oscillations are suppressed via stabilization of steady-state solutions but also
      the chaotic dynamics can be converted to periodic behavior. In all cases the
      feedback perturbation vanishes as a target state is attained.

PMID- 11969486
TI  - Phase space localization and matrix element distributions in systems with mixed
      classical phase space.
AB  - We consider distributions of diagonal matrix elements for smooth observables in
      systems whose classical phase space has a mixture of chaotic and nearly
      integrable regions. The quantum distributions agree very well with distributions
      obtained from classical trajectory segments whose length is the Heisenberg time.
      Non-Gaussian wings in the distributions can be linked to classical trapping in
      certain parts of phase space, sometimes connected to islands, but also to regions
      separated by other barriers to transport. Thus classical deviations from
      ergodicity are quantitatively reflected in quantum matrix elements. The relation
      to scars is discussed.

PMID- 11969487
TI  - Trapped to free: a mechanism to spatiotemporal chaos.
AB  - We further investigate the crisis-induced transition from temporal chaos (TC) to
      spatiotemporal chaos (STC) due to collision between the unstable orbit of a
      carrier saddle steady wave (SSW) and the attractor of its perturbation wave (PW)
      [Kaifen He, Phys. Rev. Lett. 80, 696 (1998)]. In the present work, the influence
      of the SSW on its PW is studied in different dimensions. It is found that in our
      case, as a result of mode-mode couplings only one dimension becomes crucial in
      the onset of crisis. The state transition of the PW mode phase in this dimension
      at the crisis is emphasized. Before the crisis, all the PW partial waves are
      trapped in the SSW state. After the crisis, the PW partial wave in this dimension
      is free from the trapping of the SSW partial wave; it experiences on-off
      resonance with the latter, which is responsible for the transition to STC.

PMID- 11969488
TI  - Multiphase patterns in periodically forced oscillatory systems.
AB  - Periodic forcing of an oscillatory system produces frequency locking bands within
      which the system frequency is rationally related to the forcing frequency. We
      study extended oscillatory systems that respond to uniform periodic forcing at
      one quarter of the forcing frequency (the 4:1 resonance). These systems possess
      four coexisting stable states, corresponding to uniform oscillations with
      successive phase shifts of pi/2. Using an amplitude equation approach near a Hopf
      bifurcation to uniform oscillations, we study front solutions connecting
      different phase states. These solutions divide into two groups: pi fronts
      separating states with a phase shift of pi and pi/2 fronts separating states with
      a phase shift of pi/2. We find a type of front instability where a stationary pi
      front "decomposes" into a pair of traveling pi/2 fronts as the forcing strength
      is decreased. The instability is degenerate for an amplitude equation with cubic
      nonlinearities. At the instability point a continuous family of pair solutions
      exists, consisting of pi/2 fronts separated by distances ranging from zero to
      infinity. Quintic nonlinearities lift the degeneracy at the instability point but
      do not change the basic nature of the instability. We conjecture the existence of
      similar instabilities in higher 2n:1 resonances (n=3,4, em leader) where
      stationary pi fronts decompose into n traveling pi/n fronts. The instabilities
      designate transitions from stationary two-phase patterns to traveling 2n-phase
      patterns. As an example, we demonstrate with a numerical solution the collapse of
      a four-phase spiral wave into a stationary two-phase pattern as the forcing
      strength within the 4:1 resonance is increased.

PMID- 11969489
TI  - Calculation of relaxation rates from microscopic equations of motion.
AB  - For classical systems with anharmonic forces, Newton's equations for particle
      trajectories are nonlinear, while Liouville's equation for the evolution of
      functions of position and momentum is linear and is solved by constructing a
      basis of functions in which the Liouvillian is a tridiagonal matrix, which is
      then diagonalized. For systems that are chaotic in the sense that neighboring
      trajectories diverge exponentially, the initial conditions determine the solution
      to Liouville's equation for short times; but for long times, the solutions decay
      exponentially at rates independent of the initial conditions. These are the
      relaxation rates of irreversible processes, and they arise in these calculations
      as the imaginary parts of the frequencies where there are singularities in the
      analytic continuations of solutions to Liouville's equation. These rates are
      calculated for two examples: the inverted oscillator, which can be solved both
      analytically and numerically, and a charged particle in a periodic magnetic
      field, which can only be solved numerically. In these systems, dissipation arises
      from traveling-wave solutions to Liouville's equation that couple low and high
      wave-number modes allowing energy to flow from disturbances that are coherent
      over large scales to disturbances on ever smaller scales finally becoming
      incoherent over microscopic scales. These results suggest that dissipation in
      large scale motion of the system is a consequence of chaos in the small scale
      motion.

PMID- 11969490
TI  - Synchronizing chaos in an experimental chaotic pendulum using methods from linear
      control theory.
AB  - Linear feedback control, specifically model predictive control (MPC), was used
      successfully to synchronize an experimental chaotic pendulum both on unstable
      periodic and aperiodic orbits. MPC enables tuning of the controller to give an
      optimal controller performance. That is, both the fluctuations around the target
      trajectory and the necessary control actions are minimized using a least-squares
      solution of the linearized problem. It is thus shown that linear control methods
      can be applied to experimental chaotic systems, as long as an adequate model is
      available that can be linearized along the desired trajectory. This model is used
      as an observer, i.e., it is synchronized with the experimental pendulum to
      estimate the state of the experimental pendulum. In contrast with other chaos
      control procedures like the map-based Ott, Grebogi, and York method [Phys. Rev.
      Lett. 64, 1196 (1990)], the continuous type feedback control proposed by Pyragas
      [Phys. Lett. A 170, 421 (1992)], or the feedback control method recently proposed
      by Brown and Rulkov [Chaos 7 (3), 395 (1997)], the procedure outlined in this
      paper automatically results in a choice for the feedback gains that gives optimum
      performance, i.e., minimum fluctuations around the desired trajectory using
      minimum control actions.

PMID- 11969491
TI  - Controlling chaos in low- and high-dimensional systems with periodic parametric
      perturbations.
AB  - The effect of applying a periodic perturbation to an accessible parameter of
      various chaotic systems is examined. Numerical results indicate that perturbation
      frequencies near the natural frequencies of the unstable periodic orbits of the
      chaotic systems can result in limit cycles for relatively small perturbations.
      Such perturbations can also control or significantly reduce the dimension of high
      dimensional systems. Initial application to the control of fluctuations in a
      prototypical magnetic fusion plasma device will be reviewed.

PMID- 11969492
TI  - Scar and antiscar quantum effects in open chaotic systems.
AB  - We predict and numerically observe strong periodic orbit effects in the
      properties of weakly open quantum systems with a chaotic classical limit.
      Antiscars lead to a large number of exponentially narrow isolated resonances when
      the single-channel (or tunneling) opening is located on a short unstable orbit of
      the closed system; the probability to remain in the system at long times is thus
      exponentially enhanced over the random matrix theory prediction. The distribution
      of resonance widths and the probability to remain are quantitatively given in
      terms of only the stability matrix of the orbit on which the opening is placed.
      The long-time remaining probability density is nontrivially distributed over the
      available phase space; it can be enhanced or suppressed near orbits other than
      the one on which the lead is located, depending on the periods and classical
      actions of these other orbits. These effects of the short periodic orbits on
      quantum decay rates have no classical counterpart, and first appear on times
      scales much larger than the Heisenberg time of the system. All the predictions
      are quantitatively compared with numerical data.

PMID- 11969493
TI  - Simple approach to the creation of a strange nonchaotic attractor in any chaotic
      system.
AB  - A simple approach to the creation of a strange nonchaotic attractor in any
      chaotic system is described. The main idea is to control the parameter of the
      system in such a manner that the system dynamics is expanding at some times, but
      converging at others. With this approach, a strange nonchaotic attractor can be
      found in a large region in the parameter space near the boundaries between
      chaotic and regular phases or within the chaotic region far from the regular one.
      The maximum nontrivial Lyapunov exponent of the system can pass through zero
      nonsmoothly and cannot be fitted by a linear function.

PMID- 11969494
TI  - Analytical approach for the Floquet theory of delay differential equations.
AB  - We present an analytical approach to deal with nonlinear delay differential
      equations close to instabilities of time periodic reference states. To this end
      we start with approximately determining such reference states by extending the
      Poincare-Lindstedt and the Shohat expansions, which were originally developed for
      ordinary differential equations. Then we systematically elaborate a linear
      stability analysis around a time periodic reference state. This allows us to
      approximately calculate the Floquet eigenvalues and their corresponding
      eigensolutions by using matrix valued continued fractions.

PMID- 11969495
TI  - Information operations with an excitable field.
AB  - It is well established that a traveling wave can be generated on an excitable
      field, which is described with a pair of partial differential equations for an
      activator and inhibitor. In the present paper, we use a numerical simulation to
      show that the traveling wave, or signaling pulse, can be transmitted from an
      excitable field to an opposing excitable field via an intervening passive
      diffusion field in a characteristic manner depending on the spatial geometry of
      the excitable fields. Using such characteristics, it is possible to design
      various kinds of logic gates together with a time-sequential memory device. Thus,
      these functions can perform time-sensitive operations in the absence of any
      controlling clock. It may be possible to accomplish these computations with
      excitable fields in an actual system, or to create a "field computer" composed of
      electronic active and passive units.

PMID- 11969496
TI  - Simple deterministic dynamical systems with fractal diffusion coefficients.
AB  - We analyze a simple model of deterministic diffusion. The model consists of a one
      dimensional array of scatterers with moving point particles. The particles move
      from one scatterer to the next according to a piecewise linear, expanding,
      deterministic map on unit intervals. The microscopic chaotic scattering process
      of the map can be changed by a control parameter. The macroscopic diffusion
      coefficient for the moving particles is well defined and depends upon the control
      parameter. We calculate the diffusion coefficent and the largest eigenmodes of
      the system by using Markov partitions and by solving the eigenvalue problems of
      respective topological transition matrices. For different boundary conditions we
      find that the largest eigenmodes of the map match the ones of the simple
      phenomenological diffusion equation. Our main result is that the diffusion
      coefficient exhibits a fractal structure as a function of the control parameter.
      We provide qualitative and quantitative arguments to explain features of this
      fractal structure.

PMID- 11969497
TI  - Quantum-classical correspondence in localization of eigenstates for a system
      having mixed-type classical dynamics.
AB  - We have examined the localization properties of quantum eigenstates for a system
      having mixed-type classical dynamics. Emphasis is given to the structure of
      eigenfunctions and the local spectral density of states. The nature of strongly
      localized eigenstates can be explained by considering the corresponding classical
      motion on the Kolmogorov-Arnold-Moser tori. The weak localization of nearly
      delocalized eigenstates is not a quantum effect as is dynamical localization but
      a consequence of classical dynamics.

PMID- 11969498
TI  - Efficient strategy for the occasionally proportional feedback method in
      controlling chaos.
AB  - In this work, the generic mechanism of the occasionally proportional feedback
      (OPF) technique in controlling chaos has been explored extensively. Except for
      stabilizing the unstable states that are embedded in the chaotic attractors, the
      OPF method is also found to generate a great number of new states during the
      control processes. The forms and characteristics of these new states have been
      addressed. Moreover, we clarify the roles of the parameters in the OPF method and
      this clarification leads to a practical and systematic approach in adjusting the
      parameters for control. To demonstrate the validity, an analogous electronic
      circuit of the resistively shunted Josephson junction oscillator is employed in
      addition to a numerical illustration of the logistic mapping.

PMID- 11969499
TI  - Numerical statistics of power dropouts based on the Lang-Kobayashi model.
AB  - The statistics of power dropouts in semiconductor lasers subjected to delayed
      optical feedback have been numerically investigated using the Lang-Kobayashi
      model. The data from the numerical simulations have then been used to calculate
      the probability distribution functions, mean values, and return maps of the time
      that elapses between dropouts. In addition, the transition from the "low
      frequency fluctuation" to the "coherence collapse" regime has also been
      investigated. The numerical simulations compare well with both experimental
      results, obtained from multilongitudinal mode lasers, and analytical results
      obtained from other theoretical models. Evidence of "excitability" within the
      Lang-Kobayashi model is also reported.

PMID- 11969500
TI  - Stabilizing coherent destruction of tunneling.
AB  - The localization of a tunneling particle by means of an oscillating external
      field is examined for an arbitrary doublet of tunneling states. The condition of
      degenerate Floquet levels, required for localization in a symmetric system, can
      be substantially relaxed for tunneling systems with broken symmetry. A
      synergistic effect of dynamic and static asymmetry is found, which extends the
      localization regime substantially. This generalization equally applies to
      tunneling systems coupled to a dissipative environment.

PMID- 11969501
TI  - Pattern formation and a clustering transition in power-law sequential adsorption.
AB  - We present a model that describes adsorption and clustering of particles on a
      surface. A clustering transition is found that separates between a phase of
      weakly correlated particle distributions and a phase of strongly correlated
      distributions in which the particles form localized fractal clusters. The order
      parameter of the transition is identified and the fractal nature of both phases
      is examined. The model is relevant to a large class of clustering phenomena such
      as aggregation and growth on surfaces, population distribution in cities, and
      plant and bacterial colonies, as well as gravitational clustering.

PMID- 11969502
TI  - Length and time scale divergences at the magnetization-reversal transition in the
      Ising model.
AB  - The divergences of both the length and time scales, at the magnetization-reversal
      transition in the Ising model under a pulsed field, have been studied in the
      linearized limit of the mean field theory. Both the length and time scales are
      shown to diverge at the transition point and it has been checked that the nature
      of the time scale divergence agrees well with the result obtained from the
      numerical solution of the mean field equation of motion. Similar growths in
      length and time scales are also observed, as one approaches the transition point,
      using Monte Carlo simulations. However, these are not of the same nature as the
      mean field case. Nucleation theory provides a qualitative argument that explains
      the nature of the time scale growth. To study the nature of growth of the
      characteristic length scale, we have looked at the cluster size distribution of
      the reversed spin domains and have defined a pseudocorrelation length that has
      been observed to grow at the phase boundary of the transition.

PMID- 11969503
TI  - Survival-time distribution for inelastic collapse.
AB  - In a recent publication [Phys. Rev. Lett. 81, 1142 (1998)] it was argued that a
      randomly forced particle that collides inelastically with a boundary can undergo
      inelastic collapse and come to rest in a finite time. Here we discuss the
      survival probability for the inelastic collapse transition. It is found that the
      collapse-time distribution behaves asymptotically as a power law in time, and
      that the exponent governing this decay is nonuniversal. An approximate
      calculation of the collapse-time exponent confirms this behavior and shows how
      inelastic collapse can be viewed as a generalized persistence phenomenon.

PMID- 11969504
TI  - Boundary effects in reaction-diffusion processes.
AB  - The effects of a boundary on reaction systems are examined in the framework of
      the general single-species reaction/coalescence process. The boundary naturally
      represents the reactants' container, but is applicable to exciton dynamics in a
      doped TMMC crystal. We show that a density excess, which extends into the system
      diffusively from the boundary, is formed in two dimensions and below. This
      implies a surprising result for the magnetization near a fixed spin in the
      coarsening of the one-dimensional critical Ising model. The universal,
      dimensionally dependent functional forms of this density excess are given by an
      exact solution and the field-theoretic renormalization group.

PMID- 11969505
TI  - Rigorous forward-backward semiclassical formulation of many-body dynamics.
AB  - A rigorous, yet practical semiclassical formulation of time correlation functions
      or expectation values is presented. The main idea is to combine the forward and
      backward propagation steps into a single semiclassical propagator for those
      degrees of freedom that are not probed in a calculation, while retaining an
      explicit two-propagator description of the observable low-dimensional system. The
      combined forward-backward treatment of the environment naturally leads to
      extensive cancellation and results in an action that is small on the scale of
      Planck's constant. As a consequence, the integrand is smooth and thus amenable to
      Monte Carlo sampling. At the same time, important nonclassical effects terms,
      arising from interference among multiple bounce solutions of the system
      component, are fully accounted for.

PMID- 11969506
TI  - Fragmentation of percolation clusters in general dimensions.
AB  - The scaling behavior for binary fragmentation of critical percolation clusters in
      general dimensions is investigated by Monte Carlo simulation as well as by exact
      series expansions. We obtain values of critical exponents lambda and phi
      describing the scaling of the fragmentation rate and the distribution of cluster
      masses produced by binary fragmentation. Our results for lambda and phi in two to
      nine dimensions agree with the conjectured scaling relation sigma=1+lambda-phi by
      Edwards and co-workers [Phys. Rev. Lett. 68, 2692 (1992); Phys. Rev. A 46, 6252
      (1992)], which in turn excludes the other scaling relations suggested by Gouyet
      (for d=2), and by Roux and Guyon [J. Phys. A 22, 3693 (1989)], where sigma is the
      crossover exponent for the cluster numbers in percolation theory.

PMID- 11969507
TI  - Tuning friction with noise and disorder.
AB  - We present numerical and experimental evidence which demonstrates that under
      certain conditions friction can be reduced by spatial disorder and/or thermal
      noise. We discuss possible mechanisms for this behavior.

PMID- 11969508
TI  - Phase separation in two-dimensional fluids: the role of noise.
AB  - We use a lattice Boltzmann scheme within which the noise can be turned on and off
      to investigate the effect of stochastic terms on the phase ordering of a two
      dimensional binary fluid. Sufficiently strong noise slows the growth in the
      hydrodynamic regime, changing the growth exponent alpha=2/3 to alpha=1/2.

PMID- 11969509
TI  - Effect of a random noise on scaling laws of finite Prandtl number rotating
      convection near threshold.
AB  - A generalized Swift-Hohenberg model including a weak random forcing, viewed as
      mimicking the intrinsic source of noise due to boundary defects, is used to
      reproduce the experimentally observed power-law variation of the correlation
      length of rotating convection patterns as a function of the stress parameter near
      threshold, and to demonstrate the sensitivity of the exponent to the amplitude of
      the superimposed random noise. The scaling properties of rotating convection near
      threshold are thus conjectured to be nonuniversal.

PMID- 11969510
TI  - Effect of director fluctuations on the surface tension of nematic liquid
      crystals.
AB  - We discuss the surface tension of a thermotropic nematic liquid crystal near the
      nematic-isotropic temperature. We find that certain experimentally observed
      features of the temperature trend that present difficulties to mean-field
      theoretical approaches can be attributed to director fluctuations. Our main
      result is the possibility of a minimum below T(NI) if the anchoring extrapolation
      length scales with reduced temperature in the spinodal limit as tx, with x<1. We
      also show in the case of partial nematic wetting that dampening of director
      fluctuations at the surface by anchoring at the nascent interface can reverse the
      sign of the surface tension discontinuity at T(NI).

PMID- 11969511
TI  - Nonlinear theory of dislocations in smectic crystals: an exact solution.
AB  - It is shown that the strain field of an edge dislocation in a smectic crystal
      must be described in the framework of nonlinear theory, even far away from the
      core region. We present an exact solution of this nonlinear problem. The result
      of the linear theory is recovered in the limit of large bending rigidity.

PMID- 11969512
TI  - Measurement of the surface-induced order in polymer dispersed liquid crystals: an
      approach by NMR relaxometry.
AB  - A method based on NMR relaxometry is introduced to study surface-induced order in
      the isotropic phase of confined liquid crystals. We show that the magnitude of
      the surface order parameter S0 can be obtained from an increase in the deuteron
      transverse relaxation rate T-12. The increase originates in the molecular
      diffusion between the weakly ordered surface region and disordered area in the
      rest of the cavity. No assumptions concerning the residence time of molecules at
      the surface are needed. We apply the approach to a polymer dispersed liquid
      crystal and find a temperature independent S0 of magnitude congruent with 0.08.
      This indicates that short range interactions at the interface dominate the
      behavior of S0, and that only a partial orientational wetting occurs.

PMID- 11969513
TI  - Aggregation kinetics and stability of structures formed by magnetic microspheres.
AB  - Stable rings formed by magnetization-controllable microspheres at zero field are
      observed and reported in this Rapid Communication. The magnetic microspheres were
      made by plating glass beads with a critical thickness of Ni film. We found that
      the ring leading to magnetic flux closure is the most stable configuration. At
      high concentrations, all individual rings, chains, and clusters join together to
      form a netlike structure. A computer simulation based on the dipole-dipole
      interaction, without thermal noise, has been carried out, and the results are in
      good agreement with the experimental observations. Based on an analytic approach
      we give a simple explanation of the formation and stability of rings.

PMID- 11969514
TI  - Off-equilibrium dynamics of the frustrated Ising lattice gas.
AB  - We study by means of Monte Carlo simulations the off-equilibrium properties of a
      model glass, the frustrated Ising lattice gas in three dimensions. We have
      computed typical two times quantities, such as density-density autocorrelations
      and the autocorrelation of internal degrees of freedom. We find an aging scenario
      particularly interesting in the case of the density autocorrelations in real
      space that is very reminiscent of spin glass phenomenology. While this model
      captures the essential features of structural glass dynamics, its analogy with
      spin glasses may make possible its complete description using the tools developed
      in spin glass theory.

PMID- 11969515
TI  - Thermodynamics of photons in relativistic e+e- gamma plasmas.
AB  - Thermodynamic and spectral properties of a photon gas in e(+)e(-)gamma plasmas
      are studied. The effect of a finite effective mass of a photon, associated with
      the plasma frequency cutoff, is self-consistently included. In the
      ultrarelativistic plasma, the photon spectrum turns out to be universal with the
      temperature normalized plasma frequency cutoff as a fundamental constant
      independent of plasma parameters. Such a universality does not hold in the
      nonrelativistic plasma.

PMID- 11969516
TI  - High efficiency guiding of terawatt subpicosecond laser pulses in a capillary
      discharge plasma channel.
AB  - Transmission efficiencies in excess of 75% were obtained in the optical guiding
      of subpicosecond, terawatt laser pulses in a 2-cm-long capillary discharge plasma
      channel at the Naval Research Laboratory. The guided laser beam size at the exit
      of the channel was measured using far field imaging and Thomson scattering
      techniques. The guided laser intensity was >1 x 10(17) W/cm(2) at a guided beam
      diameter of 35 microm for a propagation length of 22 Rayleigh ranges. There is
      evidence that the plasma channel extends beyond the ends of the capillary and
      affects the far field beam structure of the transmitted laser pulse.

PMID- 11969517
TI  - Model of space- and energy-dependent electron flux density.
AB  - Analytic representation for the space- and energy-dependent electron flux density
      in terms of a phenomenological model was developed. The model was applied to
      electron energy degradation in gaseous argon. Flux density data were also
      generated from Monte Carlo simulations for 0.3-3.0 keV incident electrons. These
      data were used to determine adjustable parameters in our phenomenological model.
      From the nature of the cross section input to this model, we expect that the
      scaled flux density for most atomic and molecular gases will be similar to that
      obtained in this study.

PMID- 11969518
TI  - Dark incoherent soliton splitting and "phase-memory" effects: Theory and
      experiment.
AB  - We report on an experimental observation of dark incoherent soliton Y splitting.
      The effects of incoherence on the evolution of incoherent dark soliton doublets
      are investigated both theoretically and experimentally. We show that the dynamics
      of these incoherent self-trapped entities are associated with strong "phase
      memory" effects that are otherwise absent in the linear regime.

PMID- 11969519
TI  - Marangoni convection on an inhomogeneous substrate.
AB  - We consider an inhomogeneous substrate for Marangoni convection. The
      inhomogeneity shows up in a nonuniform temperature distribution which we model by
      a periodic variation. The response can exhibit parametric resonance. Both
      resonant and nonresonant responses are considered and a possible strong effect on
      wave number selection indicated.

PMID- 11969520
TI  - Dispersion of passive particles by a quasi-two-dimensional turbulent flow.
AB  - Using the experimental data of Paret and Tabeling [Phys. Rev. Lett. 79, 4162
      (1997)] we consider in detail the dispersion of particle pairs by a two
      dimensional turbulent flow and its relation to the kinematic properties of the
      velocity field. We show that the mean square separation of a pair of particles is
      governed by rather rare, extreme events and that the majority of initially close
      pairs are not dispersed by the flow. Another manifestation of the same effect is
      the fact that the dispersion of an initially dense cluster is not the result of
      homogeneously spreading the particles within the whole system. Instead it
      proceeds through a splitting into smaller but also dense clusters. The
      statistical nature of this effect is discussed.

PMID- 11969521
TI  - Nature of the energy transfer process in compressible turbulence.
AB  - Using a two-point closure theory, the eddy-damped-quasinormal-Markovian
      approximation, we have investigated the energy transfer process and triadic
      interactions of compressible turbulence. In order to analyze the compressible
      mode directly, the Helmholtz decomposition is used. The following issues were
      addressed: (1) What is the mechanism of energy exchange between the solenoidal
      and compressible modes, and (2) is there an energy cascade in the compressible
      energy transfer process? It is concluded that the compressible energy is
      transferred locally from the solenoidal part to the compressible part. It is also
      found that there is an energy cascade of the compressible mode for high turbulent
      Mach number. Since we assume that the compressibility is weak, the magnitude of
      the compressible (radiative or cascade) transfer is much smaller than that of the
      solenoidal cascade. These results are further confirmed by studying the triadic
      energy transfer function, the most fundamental building block of the energy
      transfer.

PMID- 11969522
TI  - Time-dependent geometry and energy distribution in a spiral vortex layer.
AB  - The purpose of this paper is to study how the geometry and the spatial
      distribution of energy fluctuations of different length scales in a spiral vortex
      layer are related to each other in a time-dependent way. The numerical solution
      of Krasny [J. Comput. Phys. 65, 292 (1986)], corresponding to the development of
      the Kelvin-Helmholtz instability, is analyzed in order to determine some
      geometrical features necessary for the analysis of Lundgren's unstrained spiral
      vortex. The energy distribution of the asymptotic solution of Lundgren
      characterized by a similar geometry is investigated analytically (1) in the
      wavelet radius-scale space, with a wavelet selective in the radial direction, and
      (2) in the wavelet azimuth-scale space, with a wavelet selective in the azimuthal
      direction. Energy in the wavelet radius-scale space is organized in "blobs"
      distributed in a way determined by the Kolmogorov capacity of the spiral D(K) in
      [1,2] (which determines the rate of accumulation of spiral turns). As time
      evolves these blobs move towards the small scale region of the wavelet radius
      scale space, until their scale is of the order of the diffusive length scale
      square root[nut], where t is the time and nu is the kinematic viscosity. In
      contrast, energy in the wavelet azimuth-scale space is not localized, and is
      characterized by a shear-augmented viscous cutoff proportional to sqaure
      root[nut(3)]. An accelerated viscous dissipation of the enstrophy and energy of
      Lundgren's spiral vortex is found for D(K) > 1.75, but not for D(K) < or =1.75.

PMID- 11969523
TI  - Frozen wave induced by high frequency horizontal vibrations on a CO2 liquid-gas
      interface near the critical point.
AB  - We used the liquid-vapor equilibrium of CO2 near its critical point (T(C)-T=1 to
      150 mK) in order to study the stability of an interface between a gas and a
      liquid having close densities rho(L) approximately rho(V) when submitted to high
      frequency f (3-57.5 Hz) horizontal vibrations (of amplitude a from 0.1 to 2.5
      mm). Above a given velocity threshold (2piaf )(0) we observed a "frozen wave,"
      corresponding to an interface profile of sinelike shape which is stationary in
      the reference frame of the vibrated sample cell. By varying the vibration
      parameters, the surface tension, and the density difference between the two
      phases via the temperature, it was found that the wavelength and the amplitude of
      the stationary profile are both increasing functions of the frequency and of the
      amplitude of the vibration and that they are proportional to the capillary
      length. Our measurements are consistent with a model of inviscid and
      incompressible flow averaging the effect of the vibration over a period and
      leading to a Kelvin-Helmholtz-like instability mechanism due to the relative
      motion of the two fluids.

PMID- 11969524
TI  - Parametrically excited surface waves: two-frequency forcing, normal form
      symmetries, and pattern selection.
AB  - Motivated by experimental observations of exotic free surface standing wave
      patterns in the two-frequency Faraday experiment, we investigate the role of
      normal form symmetries in the associated pattern-selection problem. With forcing
      frequency components in ratio m/n, where m and n are coprime integers that are
      not both odd, there is the possibility that both harmonic waves and subharmonic
      waves may lose stability simultaneously, each with a different wave number. We
      focus on this situation and compare the case where the harmonic waves have a
      longer wavelength than the subharmonic waves with the case where the harmonic
      waves have a shorter wavelength. We show that in the former case a normal form
      transformation can be used to remove all quadratic terms from the amplitude
      equations governing the relevant resonant triad interactions. Thus the role of
      resonant triads in the pattern-selection problem is greatly diminished in this
      situation. We verify our general bifurcation theoretic results within the example
      of one-dimensional surface wave solutions of the Zhang-Vinals model [J. Fluid
      Mech. 341, 225 (1997)] of the two-frequency Faraday problem. In one-dimension, a
      1:2 spatial resonance takes the place of a resonant triad in our investigation.
      We find that when the bifurcating modes are in this spatial resonance, it
      dramatically effects the bifurcation to subharmonic waves in the case that the
      forcing frequencies are in ratio 1/2; this is consistent with the results of
      Zhang and Vinals. In sharp contrast, we find that when the forcing frequencies
      are in a ratio 2/3, the bifurcation to (sub)harmonic waves is insensitive to the
      presence of another spatially resonant bifurcating mode. This is consistent with
      the results of our general analysis.

PMID- 11969525
TI  - Velocity structure functions, scaling, and transitions in high-Reynolds-number
      Couette-Taylor flow.
AB  - Flow between concentric cylinders with a rotating inner cylinder is studied for
      Reynolds numbers in the range 2x10(3)<R<10(6) (Taylor Reynolds numbers, 10 <
      R(lambda)< 290) for a system with radius ratio eta=0.724. Even at the highest
      Reynolds number studied, the energy spectra do not show power law scaling (i.e.,
      there is no inertial range), and the dissipation length scale is surprisingly
      large. Nevertheless, the velocity structure functions calculated using extended
      self-similarity exhibit clear power-law scaling. The structure function exponents
      zeta(p) fit Kolmogorov's log-normal model within the experimental uncertainty,
      zeta(p)=(p/3) [1+(mu/6)(3-p)] (for p < or =10) with mu=0.27. These zeta(p) values
      are close to those found in other flows. Measurements of torque scaling are
      presented that are an order of magnitude more accurate than those previously
      reported [Lathrop et al., Phys Rev. A 46, 6390 (1992)]. Measurements of velocity
      in the fluid core reveal the presence of azimuthal traveling waves up to the
      highest Reynolds numbers examined. These waves show evidence of a transition at
      R(T)=1.3 x 10(4); this transition was observed previously in measurements of
      torque, but our wave velocity and wall shear stress measurements provide the
      first evidence from local quantities of the transition at R(T). Velocity
      measurements indicate that at R(T) there is a change in the coherent structures
      of the core flow; this is consistent with our analyses of the scaling of the
      torque. Our measurements were made at two aspect ratios, and no significant
      dependence on aspect ratio was observable for R > R(T).

PMID- 11969526
TI  - Chemical or biological activity in open chaotic flows.
AB  - We investigate the evolution of particle ensembles in open chaotic hydrodynamical
      flows. Active processes of the type A+B-->2B and A+B-->2C are considered in the
      limit of weak diffusion. As an illustrative advection dynamics we consider a
      model of the von Karman vortex street, a time-periodic two-dimensional flow of a
      viscous fluid around a cylinder. We show that a fractal unstable manifold acts as
      a catalyst for the process, and the products cover fattened-up copies of this
      manifold. This may account for the observed filamental intensification of
      activity in environmental flows. The reaction equations valid in the wake are
      derived either in the form of dissipative maps or differential equations
      depending on the regime under consideration. They contain terms that are not
      present in the traditional reaction equations of the same active process: the
      decay of the products is slower while the productivity is much faster than in
      homogeneous flows. Both effects appear as a consequence of underlying fractal
      structures. In the long time limit, the system locks itself in a dynamic
      equilibrium state synchronized to the flow for both types of reactions. For
      particles of finite size an emptying transition might also occur leading to no
      products left in the wake.

PMID- 11969527
TI  - Variational principle for the Navier-Stokes equations.
AB  - A variational principle is presented for the Navier-Stokes equations in the case
      of a contained boundary-driven, homogeneous, incompressible, viscous fluid. Based
      upon making the fluid's total viscous dissipation over a given time interval
      stationary subject to the constraint of the Navier-Stokes equations, the
      variational problem looks overconstrained and intractable. However, introducing a
      nonunique velocity decomposition, u(x,t)=phi(x,t) + nu(x,t), "opens up" the
      variational problem so that what is presumed a single allowable point over the
      velocity domain u corresponding to the unique solution of the Navier-Stokes
      equations becomes a surface with a saddle point over the extended domain
      (phi,nu). Complementary or dual variational problems can then be constructed to
      estimate this saddle point value strictly from above as part of a minimization
      process or below via a maximization procedure. One of these reduced variational
      principles is the natural and ultimate generalization of the upper bounding
      problem developed by Doering and Constantin. The other corresponds to the
      ultimate Busse problem which now acts to lower bound the true dissipation.
      Crucially, these reduced variational problems require only the solution of a
      series of linear problems to produce bounds even though their unique intersection
      is conjectured to correspond to a solution of the nonlinear Navier-Stokes
      equations.

PMID- 11969528
TI  - Experimental observations of bubble response and light intensity near the
      threshold for single bubble sonoluminescence in an air-water system.
AB  - Single bubble sonoluminescence in an air-water system has been shown to occur
      along a unique surface in the acoustic pressure-ambient radius-gas concentration
      parameter space where the bubble is stable both in shape and in (average) size.
      In this paper, we show how the bubble deviates from the expected path (traced by
      the shape-instability threshold as a function of pressure) in order to reach the
      observed stability. We also present measurements of the expansion ratio
      (R(max)/R(0)) for bubbles near the threshold for light emission. The results
      suggest that maximal bubble radial response is an insufficient criterion for the
      onset of light emission, and we present data for the dependence of the emitted
      light on several parameters.

PMID- 11969529
TI  - Hydrodynamic fluctuations in the Kolmogorov flow: linear regime.
AB  - The Landau-Lifshitz fluctuating hydrodynamics is used to study the statistical
      properties of the linearized Kolmogorov flow. The relative simplicity of this
      flow allows a detailed analysis of the fluctuation spectrum from near equilibrium
      regime up to the vicinity of the first convective instability threshold. It is
      shown that in the long time limit the flow behaves as an incompressible fluid,
      regardless of the value of the Reynolds number. This is not the case for the
      short time behavior where the incompressibility assumption leads in general to a
      wrong form of the static correlation functions, except near the instability
      threshold. The theoretical predictions are confirmed by numerical simulations of
      the full nonlinear fluctuating hydrodynamic equations.

PMID- 11969530
TI  - Testing a random phase approximation for bounded turbulent flow.
AB  - Tractable implementation of a spectral closure requires that the modal
      representation of the energy satisfy a restricted random phase approximation
      (RRPA). This condition is exactly satisfied when the statistical system is
      homogeneous and the basis functions are Fourier modes. In this case, the ensemble
      average of the spectral covariance diagonalizes, i.e.,
      <c(k(1))c(k(2))>=delta(k(1)+k(2))<c(k(1))c(k(2))>, where c(k,t) is a Fourier
      coefficient in a Galerkin representation of the velocity field. However, for
      inhomogeneous statistical systems in which the Fourier system is inappropriate,
      the RRPA requires validation. We use direct numerical simulations (DNSs) of the
      Navier-Stokes and truncated Euler equations to test the degree to which the RRPA
      is satisfied when applied to a recent representation due to Turner (LANL
      Unclassified Report No. LA-UR-96-3257) of a bounded turbulent rectangular channel
      flow with free slip, stress free walls. It is shown that a complete test of the
      RRPA for a fully inhomogeneous DNS with N3 grid points actually requires N3+1
      members in the ensemble. The "randomness" of the phase can be characterized by a
      probability density function (PDF) of the modulus of the normalized spectral
      covariance. Results reveal that for both the Navier-Stokes and Euler systems the
      PDF does not change in time as the turbulence decays, and that the PDF for the
      Euler system is virtually identical to the one produced from an ensemble of
      random fields. This result is consistent with the equipartition of energy for the
      Euler system, in which the RRPA becomes an exact result rather than an
      approximation as the number of realizations approaches N3+1. The slight
      differences observed between the PDF produced from the random fields and the one
      from the Navier-Stokes system are thus shown to be entirely a result of the
      presence of a finite viscosity. It is also shown that there is great variation
      between statistics computed over the ensemble and those for a single realization.

PMID- 11969531
TI  - Photopolarimetric characterization of the transition between two turbulent states
      in a nematic liquid crystal film.
AB  - This work was aimed at the photopolarimetric characterization of the transition
      between two dynamic scattering modes that take place in a planarly aligned
      nematic liquid crystal sample, under the effect of an external low-frequency
      electric field. The time evolution of the degree of polarization and the behavior
      of the radiation entropy of the transmitted light allow us to interpret the
      transition between two turbulent states, or dynamic scattering modes, as a decay
      from a two-dimensional (2D) to a (3D) turbulence.

PMID- 11969532
TI  - Systematic approach to bicontinuous cubic phases in ternary amphiphilic systems.
AB  - The Fourier approach and theories of space groups and color symmetries are used
      to systematically generate and compare bicontinuous cubic structures in the
      framework of a Ginzburg-Landau model for ternary amphiphilic systems. Both single
      and double structures are investigated; they correspond to systems with one or
      two monolayers in a unit cell, respectively. We show how and why single
      structures can be made to approach triply periodic minimal surfaces very closely,
      and give improved nodal approximations for G, D, I-WP, and P surfaces. We
      demonstrate that the relative stability of the single structures can be
      calculated from the geometrical properties of their interfaces only. The single
      gyroid G turns out to be the most stable bicontinuous cubic phase since it has
      the smallest porosity. The representations are used to calculate distributions of
      the Gaussian curvature and 2H-nuclear-magnetic-resonance band shapes for C(P),
      C(D), S, C(Y), and F-RD surfaces.

PMID- 11969533
TI  - Experimental test of the Warren-Langer model in nematic-isotropic planar
      interfaces.
AB  - In a directional solidification apparatus, the recoil of the nonsteady planar
      nematic-isotropic interface of the liquid crystal 8CB doped with hexachloroethane
      was measured, for different pulling velocities. Results agree very well with the
      predictions of our two-sided extension of Warren and Langer's one-sided model
      [Phys. Rev. E 47, 2702 (1993)], therefore supporting the validity of their ansatz
      about the evolution of the dopant concentration field. From the comparison
      between experiment and theory we obtain values for the segregation and diffusion
      coefficients of hexachloroethane in 8CB comparable to those found in the
      literature and measured by other methods. Using the same procedure, we measured
      the value of the segregation coefficient of 8CB doped with water as a function of
      applied sinusoidal electric field perpendicular to the sample, along the
      homeotropic direction. The segregation coefficient increases with electric field.
      In addition, preliminary results on the cellular instability in this system show
      that the capillary length of the pattern also increases with electric field. To
      our knowledge, this is the first binary system with continuously tunable
      segregation coefficient and capillary length.

PMID- 11969534
TI  - Influence of substrate microrelief on the Freedericksz transition in a thin
      nematic cell.
AB  - An effect of substrate surface regular wavy microrelief on the Freedericksz
      transition in a thin homeotropically aligned nematic cell near the smectic-A
      nematic second-order transition temperature is theoretically investigated. It is
      shown that because of the suppression of an interfacial smectic-A structure, the
      Freedericksz critical field for the cell with substrates having a sufficiently
      sharp microrelief should be significantly lower than that for the cell of the
      same thickness, but with perfectly flat substrates.

PMID- 11969535
TI  - Quasicritical behavior of dielectric permittivity in the isotropic phase of n
      hexyl-cyanobiphenyl in a large range of temperatures and pressures.
AB  - Results of studies of the dielectric permittivity and nonlinear dielectric effect
      (NDE) in the isotropic phase of n-hexyl-cyanobiphenyl are presented. The data
      reported cover both pressure and temperature dependence. Measurements under
      atmospheric pressure were carried out in a wide range, up to 100 K from the
      clearing temperature. The application of a weak measurement frequency (f=67 kHz)
      resulted in a negligible influence of relaxation processes on NDE results. For
      both temperature and pressure paths, the dielectric permittivity and the NDE
      exhibited strong pretransitional effects, described by "critical" exponents phi
      =1-alpha approximately 0.5 and gamma=1, respectively. Scaling expressions for the
      pretransitional behavior of the NDE and of the dielectric permittivity have been
      proposed. The relationship between pretransitional effects in the isotropic phase
      of nematogens and in critical solutions has also been discussed.

PMID- 11969536
TI  - Looped finger transformation in frustrated cholesteric liquid crystals.
AB  - Localized structures named "fingers" form in the vicinity of the unwinding
      transition of a cholesteric liquid crystal subjected to an electric field and to
      homeotropic boundary conditions. Several types of fingers exist, with different
      static and dynamic properties. For instance, cholesteric fingers of the second
      species (CF-2) can drift perpendicular to their axes and form spirals in ac
      electric fields, whereas fingers of the first species (CF-1) crawl along their
      axes. In this article we show that CF-2's are much easier to nucleate in thick
      samples (with respect to the pitch) than in thin ones and may form loops like the
      CF-1's, with or without defects. We show that looped CF-1's always collapse in
      thick samples at increasing voltage, whereas they can form cholesteric bubbles in
      thin samples. By contrast, we never observe the formation of a bubble from a loop
      of a CF-2 except when it possesses a point defect. We also recall that CF-1
      segments always collapse at increasing voltage, whereas CF-2 segments
      systematically give cholesteric bubbles in similar conditions. To qualitatively
      explain these transformations, we use a simplified representation on the unit
      sphere S2 of the director field within the fingers. While the CF-1's are
      described within the standard model of Press and Arrot, we use for the CF-2's a
      recent model of Gil and Gilli, which we prove to explain most observations. We
      also describe the growth and collapse dynamics of a loop of a CF-2 in close
      connection with the spiral dynamics. Finally, we show experimentally and
      numerically that the CF-2's get abruptly thinner when the electric field exceeds
      the spinodal limit of the CF-1's. This transformation is reversible, but strongly
      hysteretic.

PMID- 11969537
TI  - Dielectric and high-pressure investigations on a thermotropic cubic mesophase.
AB  - Optically isotropic cubic mesophases, which are commonly exhibited by lyotropic
      materials, have been observed in a few thermotropic liquid crystalline systems
      also. Although the first thermotropic cubic mesophase was reported about 40 years
      ago, its existence in diverse systems is only a recent finding. Moreover, the
      investigations on this mesophase have mainly concentrated on the structural
      aspects. While the effect of pressure has not been reported, only one dielectric
      measurement seems to have been carried out. In this paper we present the results
      of our dielectric and high pressure investigations on a compound exhibiting a
      thermotropic cubic mesophase. Two salient results are (i) a low frequency
      relaxation mode is observed with a large dielectric strength with appreciable
      changes across the columnar-cubic and cubic-smectic C transitions; and (ii) the
      cubic phase ceases to exist when the applied pressure exceeds about 400 bar.

PMID- 11969538
TI  - Neutron reflectivity studies of critical adsorption: the correspondence between a
      critical adsorption profile and specular neutron reflection.
AB  - For interfacial order parameter profiles which decay as Az(-mu), such as the
      composition profile of the noncritical interface of a binary liquid mixture at a
      critical end point, there is a reported one-to-one correspondence between the
      profile and the reflectivity which can be described by an analytical theory [S.
      Dietrich and R. Schack, Phys. Rev. Lett. 58, 140 (1987)]. Evidence for mu=0.53+/
      0.02 for adsorption at the hydrophilic silicon/liquid surface of the mixture (2
      butoxyethanol+deuterium oxide) near its lower critical end point, determined from
      neutron reflectivity measurements, is presented. This value is in good agreement
      with the theoretical prediction of mu=0.516+/-0.004. Further examination of the
      data permits the determination of the asymptotic surface enrichment scaling
      factor amplitude P0 approximately 0.11, which is not in agreement with the
      theoretical value P(0) = 0.94+/-0.05 and values determined by other experimental
      methods.

PMID- 11969539
TI  - Kinetic approach to granular gases.
AB  - We address the problem of the so-called "granular gases," i.e., gases of massive
      particles in rapid movement undergoing inelastic collisions. We introduce a class
      of models of driven granular gases for which the stationary state is the result
      of the balance between the dissipation and the random forces which inject
      energies. These models exhibit a genuine thermodynamic limit, i.e., at fixed
      density the mean values of kinetic energy and dissipated energy per particle are
      independent of the number N of particles, for large values of N. One has two
      regimes: when the typical relaxation time tau of the driving Brownian process is
      small compared with the mean collision time tau(c) the spatial density is nearly
      homogeneous and the velocity probability distribution is Gaussian. In the
      opposite limit tau>>tau(c) one has strong spatial clustering, with a fractal
      distribution of particles, and the velocity probability distribution strongly
      deviates from the Gaussian one. Simulations performed in one and two dimensions
      under the Stosszahlansatz Boltzmann approximation confirm the scenario.
      Furthermore, we analyze the instabilities bringing to the spatial and the
      velocity clusterization. Firstly, in the framework of a mean-field model, we
      explain how the existence of the inelasticity can lead to a spatial
      clusterization; on the other hand, we discuss, in the framework of a Langevin
      dynamics treating the collisions in a mean-field way, how a non-Gaussian
      distribution of velocity can arise. The comparison between the numerical and the
      analytical results exhibits an excellent agreement.

PMID- 11969540
TI  - Reconstruction of random media using Monte Carlo methods.
AB  - A simulated annealing algorithm is applied to the reconstruction of two
      dimensional porous media with prescribed correlation functions. The experimental
      correlation function of an isotropic sample of Fontainebleau sandstone and a
      synthetic correlation function with damped oscillations are used in the
      reconstructions. To reduce the numerical effort we follow a proposal suggesting
      the evaluation of the correlation functions only along certain directions. The
      results show that this simplification yields significantly different
      microstructures as compared to a full evaluation of the correlation function. In
      particular, we find that the simplified reconstruction method introduces an
      artificial anisotropy that is originally not present.

PMID- 11969541
TI  - Fractal growth of epitaxial surface clusters with elastic interaction.
AB  - The fractal growth of clusters adsorbed on crystal surfaces has been studied by
      Monte Carlo simulations. Elastic interactions between the atoms through the
      substrate have been included. Attractive and repulsive interaction potentials
      1/r(3) have been used, including a varying cutoff for the range of interaction.
      As an important result we find that there exists a crossover radius beyond which
      the fractal dimension of the cluster corresponds to the fractal dimension of
      conventional two-dimensional diffusion limited aggregation. The crossover radius
      itself and the properties of the cluster inside that radius depend sensitively on
      the details of the interaction. The results have been analyzed by a scaling
      theory. Furthermore, we have implemented a multigrid scheme which allows for very
      efficient simulation of a large number of mobile atoms with long-range
      interaction on the surface.

PMID- 11969542
TI  - Vesicles in solutions of hard rods.
AB  - The surface free energy of ideal hard rods near curved hard surfaces is
      determined to second order in curvature for surfaces of general shapes. In
      accordance with previous results for spherical and cylindrical surfaces it is
      found that this quantity is nonanalytical when one of the principal curvatures
      changes signs. This prohibits writing it in the common Helfrich form. It is shown
      that the nonanalytical terms are the same for any aspect ratio of the rods. These
      results are used to find the equilibrium shape of vesicles immersed in solutions
      of rodlike (colloidal) particles. The presence of the particles induces a change
      in the equilibrium shape and a shift of the prolate-oblate transition in the
      vesicle phase diagram, which are calculated within the framework of the
      spontaneous curvature model. As a consequence of the special form of the energy
      contribution due to the rods, these changes cannot be accounted for by a simple
      rescaling of the elastic constants of the vesicle as for solutions of spherical
      colloids or polymers.

PMID- 11969543
TI  - Why all crystals need not be bcc: symmetry breaking at the liquid-solid
      transition revisited.
AB  - Alexander and McTague [Phys.Rev. Lett. 41, 702 (1978)] argued that if there is a
      spinodal point associated with the liquid-solid transition in a fluid of
      spherically symmetric particles, the bcc phase will be uniquely favored as the
      only accessible symmetry breaking structure that forms a regular three
      dimensional lattice. By reconsidering their analysis in the framework of density
      functional theory, we show that at a liquid-solid spinodal in fact many other
      solid stuctures also are simultaneously accessible, among them the fcc structure.
      Nevertheless, the bcc structure is still shown to be special, as, independent of
      the details of the interaction, the free energy of the unstable bcc phase close
      to the spinodal is always lower than that of the other solidlike structures. We
      illustrate our general results by explicit calculations on a toy model, the
      "Onsager solid." This simple model also indicates that the ultimately stable
      crystal phase, which, as usual for sufficiently steep repulsive forces, turns out
      to be fcc, is dictated by properties of the free energy that cannot be obtained
      perturbatively starting from the spinodal point.

PMID- 11969544
TI  - Polymer shape anisotropy and the depletion interaction.
AB  - We calculate the second and third virial coefficients of the effective sphere
      sphere interaction due to polymer-induced depletion forces. By utilizing the
      anisotropy of a typical polymer conformation, we can consider polymers that are
      roughly the same size as the spheres. We argue that recent experiments are
      laboratory evidence for polymer shape anisotropy.

PMID- 11969545
TI  - Depolarized light scattering spectroscopy of Ca0.4K0.6(NO3)(1.4): a reexamination
      of the "knee".
AB  - The "knee" found in the depolarized light scattering spectra of
      Ca0.4K0.6(NO3)(1.4) at low temperatures by G. Li, W.M. Du, X.K. Chen, H.Z.
      Cummins, and N.J. Tao [Phys. Rev. A 45, 3867 (1992)] appears to have been an
      experimental artifact. The origin of this feature is analyzed, and its
      implications for the mode coupling theory of the liquid-glass transition are
      considered.

PMID- 11969547
TI  - Geometrical model for a particle on a rough inclined surface.
AB  - A simple geometrical model is presented for the gravity-driven motion of a single
      particle on a rough inclined surface. Adopting a simple restitution law for the
      collisions between the particle and the surface, we arrive at a model in which
      the dynamics is described by a one-dimensional map. This map is studied in detail
      and it is shown to exhibit several dynamical regimes (steady state, chaotic
      behavior, and accelerated motion) as the model parameters vary. A phase diagram
      showing the corresponding domain of existence for these regimes is presented. The
      model is also found to be in good qualitative agreement with recent experiments
      on a ball moving on a rough inclined line.

PMID- 11969546
TI  - Steps, kinetic anisotropy, and long-wavelength instabilities in directional
      solidification.
AB  - We consider the effect of anisotropic interface kinetics on long-wavelength
      instabilities during the directional solidification of a binary alloy having a
      vicinal interface. Linear theory predicts that a planar solidification front is
      stabilized under the effect of anisotropy as long as the segregation coefficient
      is small enough, whereas a novel instability appears at high rates of
      solidification. Furthermore, the neutral stability curve, indicating the values
      of the principal control parameter (here the morphological number) for which the
      growth rate of a sinusoidal perturbation of a given wavelength changes its sign,
      is shown to have up to three branches, two of them combining to form an isola for
      certain values of the control parameters. We identify conditions for which linear
      stability theory predicts the instability of the planar interface to long
      wavelength traveling waves. A number of distinguished limits provide evolution
      equations that describe the resulting dynamical behavior of the crystal-melt
      interface and generalize previous work by Sivashinsky, Brattkus, and Davis and
      Riley and Davis. Bifurcation analysis and numerical computations for the derived
      evolution equations show that the anisotropy is able to promote the tendency to
      supercritical bifurcation, and also leads to the development of strongly
      preferred interface orientations for finite-amplitude deformations.

PMID- 11969548
TI  - Effects of polymer chains on structure and dynamics of supercooled water in
      poly(vinyl alcohol).
AB  - Molecular-dynamics simulations for poly(vinyl alcohol) hydrogels have been
      carried out in a wide temperature range 150-400 K to examine effects of polymer
      chains on structure and dynamics of supercooled water in hydrogels. A fragile
      strong character of water under perturbations of polymer chains is examined.
      Polymer chains affect the fragile-strong character of water, which is manifested
      in temperature dependences of potential energy, translational diffusion
      coefficient, and orientational relaxation time. Water coexisting with polymer has
      a rather stronger character in the strong-fragile classification than that in
      pure water. Structure and dynamics of water in hydrogels are significantly
      altered by the slow dynamics of polymer chains, as well as the structure and
      dynamics of hydrogen-bond networks.

PMID- 11969549
TI  - Universal surface scaling function for critical adsorption.
AB  - We present an accurate determination of the one- and two-phase universal surface
      scaling function which describes critical adsorption at noncritical interfaces of
      critical binary liquid mixtures in the strong surface field limit. The 95%
      confidence levels for this function are also determined. This function
      quantitatively describes ellipsometric critical adsorption data for three upper
      critical and one lower critical binary liquid mixtures.

PMID- 11969550
TI  - Tubular phase of self-avoiding anisotropic crystalline membranes.
AB  - We analyze the tubular phase of self-avoiding anisotropic crystalline membranes.
      A careful analysis using renormalization group arguments together with symmetry
      requirements motivates the simplest form of the large-distance free energy
      describing fluctuations of tubular configurations. The non-self-avoiding limit of
      the model is shown to be exactly solvable. For the full self-avoiding model we
      compute the critical exponents using an epsilon expansion about the upper
      critical embedding dimension for general internal dimension D and embedding
      dimension d. We then exhibit various methods for reliably extrapolating to the
      physical point (D=2,d=3). Our most accurate estimates are nu=0.62 for the Flory
      exponent and zeta=0.80 for the roughness exponent.

PMID- 11969551
TI  - Magnetic-field-induced optical transmittance in colloidal suspensions.
AB  - Through simulation and experiment we demonstrate that when a magnetic field is
      applied to a suspension of magnetic particles, the optical attenuation length
      along the direction of the field increases dramatically, due to the formation of
      chainlike structures that allow the transmission of light between the strongly
      absorbing particles. This phenomenon is interesting for two reasons; first, there
      might be practical applications for this effect, such as optical-fiber-based
      magnetic field sensors, and second, measuring the time evolution of the optical
      attenuation length enables us to determine the kinetics of structure formation,
      which can be compared to the predictions of simulation and theory. In agreement
      with both simulation and theory, the optical attenuation length increases as a
      power of time, but much less light is actually transmitted than expected,
      especially at higher particle concentrations. We conclude that particle
      roughness, which is not included in either theory or simulation, plays a
      significant role in structural development, by pinning structures into local
      minima.

PMID- 11969553
TI  - Wetting at nonplanar substrates: unbending and unbinding.
AB  - We consider fluid wetting on a corrugated substrate using effective interfacial
      Hamiltonian theory and show that breaking the translational invariance along the
      wall can induce an unbending phase transition in addition to unbinding. Both
      first-order and second-order unbending transitions can occur at and out of
      coexistence. Results for systems with short-ranged and long-ranged forces
      establish that the unbending critical point is characterized by hyperuniversal
      scaling behavior. We show that, at bulk coexistence, the adsorption at the
      unbending critical point is a universal multiple of the adsorption for the
      correspondent planar system.

PMID- 11969552
TI  - Molecular weight distribution and the electrorheological response for anisotropic
      solutions of poly(gamma-benzyl-L-glutamate) induced by the convection of the
      electrohydrodynamic instability.
AB  - Transient responses of stress to a sinusoidal electric field were reported for
      anisotropic solutions of poly(gamma-benzyl-L-glutamate)s (PBLG's) with different
      distributions of the molecular weight. The transient stress, which was induced by
      the convection of the electrohydrodynamic instability, showed a steep and large
      increase when it was plotted against the instantaneous amplitude of the electric
      field. The maximum stress of a PBLG solution tended to increase with an increase
      in the maximum molecular weight of the PBLG in the molecular weight distribution.

PMID- 11969554
TI  - Analytic model for the ballistic adsorption of polydisperse mixtures.
AB  - We study the ballistic adsorption of a polydisperse mixture of spheres onto a
      line. Within a mean-field approximation, the problem can be analytically solved
      by means of a kinetic equation for the gap distribution. In the mean-field
      approach, the adsorbed substrate is replaced by a set of effective particles
      having the same size, equal to the average diameter of the spheres in the
      original mixture. The analytic solution in the case of binary mixtures agrees
      quantitatively with direct Monte Carlo simulations of the model, and
      qualitatively with previous simulations of a related model in d=2.

PMID- 11969555
TI  - Nonergodicity transitions in colloidal suspensions with attractive interactions.
AB  - Colloidal gel and glass transitions are investigated using the idealized mode
      coupling theory (MCT) for model systems characterized by short-range attractive
      interactions. Results are presented for adhesive hard sphere and hard core
      attractive Yukawa systems. According to MCT, the former system shows a critical
      glass transition concentration that increases significantly with introduction of
      a weak attraction. For the latter attractive Yukawa system, MCT predicts low
      temperature nonergodic states that extend to the critical and subcritical region.
      Several features of the MCT nonergodicity transition in this system agree
      qualitatively with experimental observations on the colloidal gel transition,
      suggesting that the gel transition is caused by a low temperature extension of
      the glass transition. The range of the attraction is shown to govern the way the
      glass transition line traverses the phase diagram relative to the critical point,
      analogous to findings for the fluid-solid freezing transition.

PMID- 11969556
TI  - Heap corrugation and hexagon formation of powder under vertical vibrations.
AB  - We report free-surface instabilities in a deep bed of fine granular material of
      irregular shape under vertical vibrations. At low frequency of vibration, the
      conical heap due to convective flow becomes unstable above a critical amplitude
      of vibration and acquires an azimuthal dependence which makes the heap surface
      corrugated. At even higher amplitude, the heap is no longer stable and splits
      into small heaps on a hexagonal lattice. At high frequency, we observe standing
      waves (stripes) at the same frequency as the driving one. The main mechanism of
      these instabilities can be traced back to the presence of the surrounding gas,
      since they vanish under vacuum conditions.

PMID- 11969557
TI  - Stability and structure of a supercooled liquid mixture in two dimensions.
AB  - The structural and thermodynamic properties of a two-dimensional binary mixture
      of soft discs are reported over a range of temperatures down to large
      supercoolings using constant NPT molecular dynamics simulations. It is shown that
      the four orders of magnitude increase in the structural relaxation time is not
      accompanied by any significant increase in translational or orientational order.
      The phase diagram, calculated in the temperature/composition plane using
      thermodynamic integration, exhibits a deep eutectic point that is responsible for
      stabilizing the amorphous state. Voronoi analysis of the low-temperature ground
      state reveals a structure characterized by a network of linear arrays of fivefold
      and sevenfold sites. The heat capacity C(P) exhibits an asymmetric peak with a
      maximum at T(*)=0.55. It is argued that the initial rapid drop in C(P) for
      T*<0.55 is an equilibrium result and, hence, the peak in the heat capacity
      corresponds to the existence of an "enthalpy gap" with a characteristic
      temperature of T* approximately 0.35. This gap results from a minimum volume
      change associated with an anharmonic fluctuation.

PMID- 11969558
TI  - Phase diagram of highly asymmetric binary hard-sphere mixtures.
AB  - We study the phase behavior and structure of highly asymmetric binary hard-sphere
      mixtures. By first integrating out the degrees of freedom of the small spheres in
      the partition function we derive a formal expression for the effective
      Hamiltonian of the large spheres. Then using an explicit pairwise (depletion)
      potential approximation to this effective Hamiltonian in computer simulations, we
      determine fluid-solid coexistence for size ratios q=0.033, 0.05, 0.1, 0.2, and
      1.0. The resulting two-phase region becomes very broad in packing fractions of
      the large spheres as q becomes very small. We find a stable, isostructural solid
      solid transition for q< or =0.05 and a fluid-fluid transition for q< or =0.10.
      However, the latter remains metastable with respect to the fluid-solid transition
      for all size ratios we investigate. In the limit q-->0 the phase diagram mimics
      that of the sticky-sphere system. As expected, the radial distribution function
      g(r) and the structure factor S(k) of the effective one-component system show no
      sharp signature of the onset of the freezing transition and we find that at most
      points on the fluid-solid boundary the value of S(k) at its first peak is much
      lower than the value given by the Hansen-Verlet freezing criterion. Direct
      simulations of the true binary mixture of hard spheres were performed for q > or
      =0.05 in order to test the predictions from the effective Hamiltonian. For those
      packing fractions of the small spheres where direct simulations are possible, we
      find remarkably good agreement between the phase boundaries calculated from the
      two approaches-even up to the symmetric limit q=1 and for very high packings of
      the large spheres, where the solid-solid transition occurs. In both limits one
      might expect that an approximation which neglects higher-body terms should fail,
      but our results support the notion that the main features of the phase equilibria
      of asymmetric binary hard-sphere mixtures are accounted for by the effective
      pairwise depletion potential description. We also compare our results with those
      of other theoretical treatments and experiments on colloidal hard-sphere
      mixtures.

PMID- 11969559
TI  - Photoacoustic generation for a spherical absorber with impedance mismatch with
      the surrounding media.
AB  - Pressure generation in a spherical absorber due to energy deposition from pulsed
      lasers is studied. For a variety of conditions, analytical solutions are derived
      that allow quick computation of exact results. For the special case of identical
      acoustic impedance, the pressure transient spreads to the surrounding medium by a
      single compressive pulse followed by a tensile pulse at the end of illumination.
      For the general case of impedance mismatch, the pressure transient is in the form
      of a series of dampened compressive and tensile pressure pulses. In this paper
      both the amplitude ratio and the sign of consecutive pressure pulses are
      determined analytically, and are shown to be dependent upon the impedance
      mismatch. For laser pulses of duration much less than the absorber's
      characteristic oscillation time, a stress confinement limit is reached for most
      of the absorber, but a sharp tensile stress in the core region of the sphere is
      predicted. This region of high stress is defined by r < or =r(c), and we show
      that r(c) is proportional to the laser pulse duration tau(0). Upon further
      shortening of the laser pulse duration, the strength of this tensile stress
      continues to increase while its spatial distribution is sharpened. This
      observation has relevance to a number of experiments where laser-induced pressure
      transients cause the absorber to fracture.

PMID- 11969560
TI  - Off-lattice model for the phase behavior of lipid-cholesterol bilayers.
AB  - Lipid bilayers exhibit a phase behavior that involves two distinct, but coupled,
      order-disorder processes, one in terms of lipid-chain crystalline packing
      (translational degrees of freedom) and the other in terms of lipid-chain
      conformational ordering (internal degrees of freedom). Experiments and previous
      approximate theories have suggested that cholesterol incorporated into lipid
      bilayers has different microscopic effects on lipid-chain packing and
      conformations and that cholesterol thereby leads to decoupling of the two
      ordering processes, manifested by a special equilibrium phase, "liquid-ordered
      phase," where bilayers are liquid (with translational disorder) but lipid chains
      are conformationally ordered. We present in this paper a microscopic model that
      describes this decoupling phenomena and which yields a phase diagram consistent
      with experimental observations. The model is an off-lattice model based on a two
      dimensional random triangulation algorithm and represents lipid and cholesterol
      molecules by hard-core particles with internal (spin-type) degrees of freedom
      that have nearest-neighbor interactions. The phase equilibria described by the
      model, specifically in terms of phase diagrams and structure factors
      characterizing different phases, are calculated by using several Monte Carlo
      simulation techniques, including histogram and thermodynamic reweighting
      techniques, finite-size scaling as well as non-Boltzmann sampling techniques (in
      order to overcome severe hysteresis effects associated with strongly first-order
      phase transitions). The results provide a consistent interpretation of the
      various phases of phospholipid-cholesterol binary mixtures based on the
      microscopic dual action of cholesterol on the lipid-chain degrees of freedom. In
      particular, a distinct small-scale structure of the liquid-ordered phase has been
      identified and characterized. The generic nature of the model proposed holds a
      promise for a unifying description for a whole series of different lipid-sterol
      mixtures.

PMID- 11969561
TI  - Late stage kinetics of a phase separation induced by a cw laser wave in binary
      liquid mixtures.
AB  - cw laser waves can be used to locally induce phase transitions. We investigate
      experimentally and theoretically a laser-driven liquid-liquid phase separation in
      a micellar phase of microemulsion and analyze its late stage kinetics. The medium
      is optically quenched in composition in the metastable region of the phase
      diagram. Two processes can lead to these concentration variations:
      electrostriction and thermodiffusion. The first originates from induced dipolar
      couplings in a field gradient. The second corresponds to a variation in
      concentration driven by a small thermal gradient. Since the nucleated droplets
      are optically trapped by the beam, we show that it becomes possible to
      experimentally analyze an academic situation, i.e., the diffusion-driven growth
      of a single droplet in compensated gravity. The late stage of this kinetics can
      be divided into two parts, a bulk behavior and a regime controlled by the finite
      transverse size of the beam. The bulk regime is totally analogous to that
      observed in classical situations (R proportional, variant t(1/3), where R is the
      droplet radius and t the time), and the scaling of the amplitudes in terms of
      reduced length and time scales is in total agreement with the expected behaviors
      for fluids belonging to the same Ising universality class. Moreover, the Gaussian
      beam behaves as an optical bottle with "soft walls" in which the absence of rigid
      boundaries, and thus of wetting couplings, allows an intrinsic description of the
      influence of finite-size effects on the kinetics. The beam size breaks the
      dynamic universality when the growing domains start to feel it. We experimentally
      investigate the resulting slowing down, and a diffusion-driven model of the
      growth inside a laser wave is built for comparison. The good agreement observed
      for the bulk regime and during its modification induced by finite-size effects
      opens a promising field for the development of this new application of laser
      waves to control out-of-equilibrium liquid mixtures.

PMID- 11969562
TI  - Hysteresis and avalanches in two-dimensional foam rheology simulations.
AB  - Foams have unique rheological properties that range from solidlike to fluidlike.
      We study two-dimensional noncoarsening foams of different disorder under shear in
      a Monte Carlo simulation, using a driven large-Q Potts model. Simulations of
      periodic shear on an ordered foam show several different response regimes. At
      small strain amplitudes, bubbles deform and recover their shapes elastically, and
      the macroscopic response is that of a linear elastic cellular material. For
      increasing strain amplitude, the energy-strain curve starts to exhibit hysteresis
      before any topological rearrangements occur, indicating a macroscopic
      viscoelastic response. When the applied strain amplitude exceeds a critical
      value, the yield strain, topological rearrangements occur, the foam starts to
      flow, and we observe macroscopic irreversibility. We find that the dynamics of
      topological rearrangements depend sensitively on the structural disorder.
      Structural disorder decreases the yield strain; sufficiently high disorder
      changes the macroscopic response of a foam from a viscoelastic solid to a
      viscoelastic fluid. This wide-ranging dynamical response and the associated
      history effects of foams result from avalanchelike rearrangement events. The
      spatiotemporal statistics of rearrangement events do not display long-range
      correlations for ordered foams or at low shear rates, consistent with
      experimental observations. As the shear rate or structural disorder increases,
      the topological events become more correlated and their power spectra change from
      that of white noise toward 1/f noise. Intriguingly, the power spectra of the
      total stored energy also exhibit this 1/f trend.

PMID- 11969563
TI  - Free energy of a long, flexible, self-avoiding polymer chain in a tube.
AB  - The confinement free energy of a long, flexible, self-avoiding polymer chain,
      fluctuating in d spatial dimensions in an infinitely long cylindrical tube with
      diameter L, is given by DeltaF approximately Ak(B)TL(-1)R(parallel) for
      R(parallel)>>L. Here R(parallel) is the length of tube occupied by the chain, and
      A is a universal amplitude. We show how to determine DeltaF and R(parallel) from
      the correlation length xi(L)(t) of the n-vector model of magnetism in the limit n
      ->0, defined on the cylindrical volume, near the critical temperature t(c)(L)
      where xi(L) diverges. Using this correspondence, we estimate A in two dimensions
      from transfer-matrix data for self-avoiding walks on strips of width L with free,
      critically absorbing, and periodic boundaries. Our results for the universal
      amplitudes A and B approximately LR(-1)(parallel)<w(2)>, where w is the winding
      number, are in excellent agreement with Monte Carlo simulations of Frauenkron,
      Causo, and Grassberger for strips with periodic boundaries.

PMID- 11969564
TI  - Scaling properties of maximally compact chains.
AB  - Scaling of the exact function for the number of intramolecular nonbonded contacts
      in a single maximally compact linear homopolymer on hypercubic lattices is
      determined as a function of number N of monomers and dimension d. A
      representative maximally compact structure is designed and an exact recursive
      expression for the maximum number m(max) of contacts is derived from that design.
      The equivalent nonrecursive expression yields the asymptotic scaling of m(max) as
      (d-1)N-dN(Delta)+1, with Delta=(d-1)/d. Implications in polymer and protein
      studies are discussed.

PMID- 11969565
TI  - Surface fractals probed by adsorbate spin-lattice relaxation dispersion.
AB  - Spin-lattice relaxation of strong adsorbates confined in disordered structures
      such as porous silica glass is treated on the basis of a relaxation mechanism due
      to "reorientation mediated by translational displacements." In such a situation
      the low-frequency spin-lattice relaxation dispersion beyond the regime where
      local reorientations dominate reflects molecular dynamics as well as the surface
      geometry on a length scale longer than 1 nm. It is shown that the power law
      frequently observed for the spin-lattice relaxation dispersion in porous media
      can be traced back to surface fractality. The fractal properties of rough
      surfaces and the statistics governing surface displacements enter explicitly in
      the expression for the dipolar correlation function. The surface fractal
      dimension can thus be evaluated from the low-frequency spin-lattice relaxation
      dispersion accessible by field-cycling NMR relaxometry.

PMID- 11969566
TI  - Propagating front in an excited granular layer.
AB  - A partial monolayer of approximately 20 000 uniform spherical steel beads,
      vibrated vertically on a flat plate, shows remarkable ordering transitions and
      cooperative behavior just below 1g maximum acceleration. We study the stability
      of a quiescent disordered or "amorphous" state formed when the acceleration is
      switched off in the excited "gaseous" state. The transition from the amorphous
      state back to the gaseous state upon increasing the plate's acceleration is
      generally subcritical: An external perturbation applied to one bead initiates a
      propagating front that produces a rapid transition. We measure the front velocity
      as a function of the applied acceleration. This phenomenon is explained by a
      model based on a single vibrated particle with multiple attractors that is
      perturbed by collisions. A simulation shows that a sufficiently high rate of
      interparticle collisions can prevent trapping in the attractor corresponding to
      the nonmoving ground state.

PMID- 11969567
TI  - Electrostriction of a near-critical fluid in microgravity.
AB  - We used interferometry to measure the electric-field-induced (i.e.,
      electrostrictive) increase of the density of sulfur hexafluoride (SF6) near its
      critical point. The results at three temperatures (T(c)+5.0 mK, T(c)+10.0 mK,
      T(c)+30.0 mK with T(c)=319 K) agree with a calculation based on the Clausius
      Mossotti relation and the restricted cubic model equation of state. To measure
      electrostriction, an inhomogeneous electric field (< or =26 kV/cm) was applied to
      the SF6 sample by charging a fine wire that passed through it. These measurements
      were performed in microgravity so that the small electrostrictive density changes
      (< or =3.5% in this paper) would not be complicated by stratification of the
      fluid's density induced by the Earth's gravity. The predicted shifts of the
      critical temperature and density resulting from the electric field were too small
      to detect.

PMID- 11969568
TI  - Properties of layer-by-layer vector stochastic models of force fluctuations in
      granular materials.
AB  - We attempt to describe the stress distributions of granular packings using
      lattice-based layer-by-layer stochastic models that satisfy the constraints of
      force and torque balance and nontensile forces at each site. The inherent
      asymmetry in the layer-by-layer approach appears to lead to an asymmetric force
      distribution, in disagreement with both experiments and general symmetry
      considerations. The vertical force component probability distribution is robust
      and in agreement with predictions of the scalar q model of Liu et al. [Science
      269, 513 (1995)] and Coppersmith et al. [Phys. Rev. E 53, 4673 (1996)] while the
      distribution of horizontal force components is qualitatively different and
      depends on the details of implementation.

PMID- 11969569
TI  - Frictional mechanics of wet granular material.
AB  - The mechanical response of a wet granular layer to imposed shear is studied
      experimentally at low applied normal stress. The granular material is immersed in
      water and the shear is applied by sliding a plate resting on the upper surface of
      the layer. We monitor simultaneously the horizontal and the vertical
      displacements of the plate to submicron accuracy with millisecond time
      resolution. The relations between the plate displacement, the dilation of the
      layer and the measured frictional force are analyzed in detail. When slip begins,
      the dilation increases exponentially over a slip distance comparable to the
      particle radius. We find that the total dilation and the steady state frictional
      force do not depend on the driving velocity, but do depend linearly on the
      applied normal stress. The frictional force also depends linearly on the dilation
      rate (rather than the dilation itself), and reaches a maximum value during the
      transient acceleration. We find that the layer can temporarily sustain a shear
      stress that is in excess of the critical value that will eventually lead to slip.
      We describe an empirical model that describes much of what we observe. This model
      differs in some respects from those used previously at stresses 10(6) times
      larger.

PMID- 11969570
TI  - Anisotropic scattering profiles of charged gels in a deformed state.
AB  - The structure factor of weakly charged polymer gels under external mechanical
      strain is calculated considering both thermal and frozen concentration
      fluctuations as well as the screening of ionic interactions. The butterfly
      patterns are discussed based on our result.

PMID- 11969571
TI  - Dense fluid transport for inelastic hard spheres.
AB  - The revised Enskog theory for inelastic hard spheres is considered as a model for
      rapid flow granular media at finite densities. A normal solution is obtained via
      the Chapman-Enskog method for states near the local homogeneous cooling state.
      The analysis is performed to first order in the spatial gradients, allowing
      identification of the Navier-Stokes order transport coefficients associated with
      the heat and momentum fluxes. In addition, the cooling rate is calculated to
      first order in the gradients and expressed in terms of the transport
      coefficients. The transport coefficients are determined from linear integral
      equations analogous to those for elastic collisions. The solubility conditions
      for these equations are confirmed and the transport coefficients are calculated
      as explicit functions of the density and restitution coefficient using a Sonine
      polynomial expansion. The results are not limited to small dissipation. Finally,
      the analysis is repeated using a simpler kinetic model. Excellent agreement is
      obtained with the results from the revised Enskog equation.

PMID- 11969572
TI  - Asymptotic solution for solitary waves in a chain of elastic spheres.
AB  - We consider a solitary wave in a chain of contacting, but initially unstressed,
      particles between which the compressive force F as a function of relative
      approach x is F=kx(n). By "initially unstressed" we mean that there is zero
      contact force between neighboring particles that are infinitely far from the
      crest of the wave. For a chain of elastic spheres in Hertzian contact, n=3 / 2.
      In this work, n is treated as "slightly" greater than 1, and an asymptotic
      solution for the solitary wave is developed in terms of the associated small
      parameter. The solution for the propagating velocity wave is found as a slightly
      perturbed Gaussian. Comparison with numerics shows that the asymptotic solution
      is very good even for the fairly large value of n=3 / 2 and is substantially more
      accurate than the presently available approximate solution given by Nesterenko.

PMID- 11969573
TI  - Noise and periodic modulations in neural excitable media.
AB  - We have analyzed the interplay between noise and periodic modulations in a mean
      field model of a neural excitable medium. For this purpose, we have considered
      two types of modulations, namely, variations of the resistance and oscillations
      of the threshold. In both cases, stochastic resonance is present, irrespective of
      whether the system is monostable or bistable.

PMID- 11969575
TI  - Global stability analysis in delayed cellular neural networks.
AB  - In this paper, the author analyzes further problems of global stability for a
      class of cellular neural networks with delays by means of the Lyapunov functional
      method, inequalities a(2)+b(2)> or =2ab and a(3)+b(3)+c(3)> or =3abc (a,b,c > or
      =0) analysis technique, some stability criteria are obtained under more general
      conditions. These criteria can be applied to design globally stable networks and
      thus have important significance in both theory and applications.

PMID- 11969574
TI  - Folding a protein by discretizing its backbone torsional dynamics.
AB  - The aim of this work is to provide a coarse codification of local conformational
      constraints associated with each folding motif of a peptide chain in order to
      obtain a rough solution to the protein folding problem. This is accomplished by
      implementing a discretized version of the soft-mode dynamics on a personal
      computer (PC). Our algorithm mimics a parallel process as it evaluates concurrent
      folding possibilities by pattern recognition. It may be implemented in a PC as a
      sequence of perturbation-translation-renormalization (p-t-r) cycles performed on
      a matrix of local topological constraints (LTM). This requires suitable
      representational tools and a periodic quenching of the dynamics required for
      renormalization. We introduce a description of the peptide chain based on a local
      discrete variable the values of which label the basins of attraction of the
      Ramachandran map for each residue. Thus, the local variable indicates the basin
      in which the torsional coordinates of each residue lie at a given time. In
      addition, a coding of local topological constraints associated with each
      secondary and tertiary structural motif is introduced. Our treatment enables us
      to adopt a computation time step of 81 ps, a value far larger than hydrodynamic
      drag time scales. Folding pathways are resolved as transitions between patterns
      of locally encoded structural signals that change within the 10 micros-100 ms
      time scale range. These coarse folding pathways are generated by the periodic
      search for structural patterns in the time-evolving LTM. Each pattern is recorded
      as a contact matrix, an operation subject to a renormalization feedback loop. The
      validity of our approach is tested vis-a-vis experimentally-probed folding
      pathways eventually generating tertiary interactions in proteins which recover
      their active structure under in vitro renaturation conditions. As an
      illustration, we focus on determining significant folding intermediates and late
      kinetic bottlenecks that occur within the first 10 ms of the bovine pancreatic
      trypsin inhibitor renaturation process. The probed cooperativity and nucleation
      effects, as well as diffusion-collision stabilization of secondary structure are
      shown to result from the persistence of relatively stable patterns through
      successive (p-t-r) cycles, thus acting as seeding patterns for further growth or
      hierarchical development.

PMID- 11969576
TI  - 13C-13C rotational resonance in a transmembrane peptide: a comparison of the
      fluid and gel phases.
AB  - A comparative study of two doubly 13C labeled amphiphilic transmembrane peptides
      was undertaken to determine the potential of rotational resonance for measuring
      internuclear distances through the direct dipolar coupling in the presence of
      motion. The two peptides, having the sequence acetyl-K2-G-L16-K2-A-amide,
      differed only in the position of 13C labels. The first peptide, [1
      13C]leu(11):[alpha-13C]leu(12), had labels on adjacent residues, at the carbonyl
      of leu(11) and the alpha carbon of leu(12). The second, [1-13C]leu(8):[alpha
      (13)/C]leu(11), was labeled on consecutive turns of the alpha-helical peptide.
      The internuclear distance between labeled positions of the first peptide, which
      for an ideal alpha helix has a value of 2.48 A, is relatively independent of
      internal flexibility or peptide conformational change. The dipolar coupling
      between these two nuclei is sensitive to motional averaging by molecular
      reorientation, however, making this peptide ideal for investigating these
      motions. The internuclear distance between labels on the second peptide has an
      expected static ideal alpha-helix value of 4.6 A, but this is sensitive to
      internal flexibility. In addition, the dipolar coupling between these two nuclei
      is much weaker because of their larger separation, making this peptide a much
      more difficult test of the rotational resonance technique. The dipolar couplings
      between the labeled nuclei of these two peptides were measured by rotational
      resonance in the dry peptide powders and in multilamellar dispersions with
      dimyristoylphosphatidylcholine in the gel phase, at -10 degrees C, and in the
      fluid phase, at 40 degrees C. The results for the peptide having adjacent labels
      can be readily interpreted in terms of a simple model for the peptide motion. The
      results for the second peptide show that, in the fluid phase, the motionally
      averaged dipolar coupling is too small to be measured by rotational resonance.
      Rotational resonance, rotational echo double resonance, and related techniques
      can be used to obtain reliable and valuable dipolar couplings in static solid and
      membrane systems. The interpretation of these couplings in terms of internuclear
      distances is straightforward in the absence of molecular motion. These techniques
      hold considerable promise for membrane protein structural studies under
      conditions, such as at low temperatures, where molecular motion does not modulate
      the dipolar couplings. However, a typical membrane at physiological temperatures
      exhibits complex molecular motions. In the absence of an accurate and detailed
      description of both internal and whole body molecular motions, it is unlikely
      that techniques of this type, which are based on extracting distances from direct
      internuclear dipolar couplings, can be used to study molecular structure under
      these conditions. Furthermore, the reduction in the strengths of the dipolar
      couplings by these motions dramatically reduces the useful range of distances
      which can be measured.

PMID- 11969577
TI  - Charge optimization leads to favorable electrostatic binding free energy.
AB  - Variational optimization of molecular electrostatic charge distributions is a
      tool for the study of association reactions of molecules in solution. In
      principle, this method can be used in drug design and protein folding to analyze
      and improve molecular interactions and to provide electrostatic templates for
      molecular design. This optimization problem reduces to an inverse source problem
      in classical electrostatics, where the sources are determined by a combination of
      external and self-polarization potentials. In this paper, we show that the
      electrostatic portion of the free energy of association for electrostatically
      optimized molecules has an upper bound of zero in many situations of physical
      interest. That is, variational optimization provides a ligand-charge distribution
      that contributes favorably to the energetics of binding, even in a strongly polar
      medium. This stabilizing effect on association reactions is contrary to the usual
      role of electrostatics in aqueous complexes, in which desolvation effects
      generally dominate. We also show the existence and nonuniqueness of the
      variational solution and make a connection to the electrostatic image charge
      problem.

PMID- 11969578
TI  - Comparison between the role of discontinuities in cardiac conduction and in a one
      dimensional hardware model.
AB  - In real electrophysiological experiments, irregularities in the extracellular
      excitation spread are believed to depend on cardiac tissue microstructure. An
      electronic hardware model was developed to analyze this dependence by placing
      some inhomogeneities (slow propagation areas) in the medium. The position of such
      inhomogeneities is correlated with abnormal delays and irregularities measured in
      signal propagation.

PMID- 11969579
TI  - Fractal ion-channel behavior generates fractal firing patterns in neuronal
      models.
AB  - Fractal behavior has been observed in both ion-channel gating and neuronal
      spiking patterns, but a causal relationship between the two has not yet been
      established. Here, we examine the effects of fractal ion-channel activity in
      modifications of two classical neuronal models: Fitzhugh-Nagumo (FHN) and Hodgkin
      Huxley (HH). For the modified FHN model, the recovery variable was represented as
      a population of ion channels with either fractal or Markov gating
      characteristics. Fractal gating characteristics changed the form of the
      interspike interval histogram (ISIH) and also induced fractal behavior in the
      firing rate. For the HH model, the K+ conductance was represented as a collection
      of ion channels with either quasifractal or Markov gating properties. Fractal
      gating induced fractal-rate behavior without changing the ISIH. We conclude that
      fractal ion-channel gating activity is sufficient to account for fractal-rate
      firing behavior.

PMID- 11969580
TI  - Unfolded in vacuo lysozyme folds into native, quasinative, and compact
      structures.
AB  - We show that the relaxation dynamics of unfolded in vacuo lysozyme is not random.
      Analyses of molecular dynamics trajectories in a convenient space of molecular
      shape descriptors reveal a "favored" pattern of transitions leading to stable
      conformations. The relaxation paths exhibit a balanced change in shape features:
      globular spheroids are formed slowly enough to allow the proper entanglement of
      secondary-structural elements. The present study shows that a protein in vacuo
      can actually (re)fold into native and quasinative structures. The driving force
      for these transformations is intrinsic to the polypeptide chain.

PMID- 11969581
TI  - Collective membrane motions in the mesoscopic range and their modulation by the
      binding of a monomolecular protein layer of streptavidin studied by dynamic light
      scattering.
AB  - Using a dedicated dynamic light scattering setup, we have studied the angstrom
      scale amplitude undulations of freely suspended planar lipid bilayers, so-called
      black lipid membranes (BLM's), over a previously not accessible spread of
      frequencies (relaxation times ranging from 10(-2) to 10(-6) s) and wave vectors
      (250 cm(-1)<q<35 000 cm(-1)). This allowed a critical test of a simple
      hydrodynamic theory of collective membrane modes, and the results obtained for a
      synthetic lecithin BLM are found to be in excellent agreement with the
      theoretical predictions. In particular, the transition of the transverse shear
      mode of a BLM between an oscillatory or propagating regime and an overdamped
      regime by passing through a bifurcation point was clearly observed. It is shown
      that the collective motions in the time- and wave-vector regime covered are
      dominated by the membrane tension, while membrane curvature does not contribute.
      The binding of the protein streptavidin to the BLM via membrane anchored specific
      binders (receptors) causes a drastic change in frequency and amplitude of the
      collective motions, resulting in a drastic increase of the membrane tension by a
      factor of 3. This effect is probably caused by a steric hindrance of the
      transverse shear motions of the lipid by the tightly bound proteins.

PMID- 11969582
TI  - Simplified calculation of folding energies and residue coordination numbers in
      random heteropolymers.
AB  - I develop a formalism for calculating effective pair and higher-order
      interactions between residues in random heteropolymers that approximately predict
      the folding enthalpy and the coordination numbers of individual residues. In a
      simple model heteropolymer with additive couplings between residues, the folding
      enthalpy is written in terms of two-, three-, and four-body interactions between
      residues. The coordination numbers are expressed in terms of interactions between
      up to three residues. Application to a 6x6 square model shows that the folding
      enthalpy is obtained to an accuracy of better than 1%. The coordination numbers
      are obtained with a rms error of 1.2 neighbors.

PMID- 11969583
TI  - Large-scale optimization of neuron arbors.
AB  - At the global as well as local scales, some of the geometry of types of neuron
      arbors-both dendrites and axons-appears to be self-organizing: Their
      morphogenesis behaves like flowing water, that is, fluid dynamically; waterflow
      in branching networks in turn acts like a tree composed of cords under tension,
      that is, vector mechanically. Branch diameters and angles and junction sites
      conform significantly to this model. The result is that such neuron tree samples
      globally minimize their total volume-rather than, for example, surface area or
      branch length. In addition, the arbors perform well at generating the cheapest
      topology interconnecting their terminals: their large-scale layouts are among the
      best of all such possible connecting patterns, approaching 5% of optimum. This
      model also applies comparably to arterial and river networks.

PMID- 11969584
TI  - Electronic transmission properties in a mesoscopic necklace with inhomogeneous
      magnetic flux.
AB  - The electronic transmission properties and the energy spectrum of a mesoscopic
      necklace with inhomogeneous flux is calculated. We found interesting transmission
      behavior that is quite different from the case with homogenous flux. In this
      model, the transmission depends on both the modulation mode and the amplitude of
      the flux. The electronic transmission properties can be explained from the energy
      spectrum of the system.

PMID- 11969586
TI  - Effects of entropy inhomogeneity on density-temperature correlation in solar
      wind.
AB  - Compressive fluctuations in solar wind slow speed streams are studied by means of
      a magnetohydrodynamics (MHD) model, which represents the plasma in the vicinity
      of the heliospheric current sheet. The model contains a current sheet, as well as
      density and temperature variations, corresponding to a large scale modulation of
      the specific entropy. Alfvenic fluctuations are initially superimposed on the
      background equilibrium and compressive fluctuations are consequently generated
      during the time evolution. The resulting correlation between density and
      temperature fluctuations at various spatial scales is interpreted in terms of
      both generation of magnetosonic fluctuations and of an "entropy cascade." The
      latter phenomenon arises as a consequence of the interaction between the MHD
      turbulence and the underlying large scale entropy structure. In particular, it is
      responsible for anticorrelated density and temperature fluctuations detected at
      various scales. The results of the model are compared with the proton density
      temperature correlation calculated during several crossings of solar wind slow
      speed streams by the Helios spacecraft. The model reproduces to a good extent the
      main observed features, in particular the dependence of the correlation
      coefficient on location (close to or far from the current sheet) and on the
      fluctuation scale. The results show that large scale inhomogeneities, in
      particular, that of specific entropy, are important ingredients in the dynamics
      of the MHD turbulence in slow speed streams.

PMID- 11969585
TI  - Dynamical properties of random charge fluctuations in a dusty plasma with
      different charging mechanisms.
AB  - A dust particle in a plasma acquires electric charge by collecting electrons and
      ions, and sometimes by emitting electrons. The charging currents consist of
      discrete charges, causing the charge to fluctuate around an equilibrium value. We
      developed a model yielding a general expression for the charge fluctuations'
      temporal autocorrelation function. Both the magnitude and characteristic time of
      fluctuations can be obtained, knowing the specific form of charging currents.
      Numerical results are presented for different charging mechanisms, including
      charging by thermionic and photoelectric emission. It is shown that for all
      charging mechanisms the amplitude of fluctuations varies as DeltaZ = alpha square
      root [</Z/>], where <Z> is the equilibrium dust grain charge in units of electron
      charges.

PMID- 11969587
TI  - Magnetic focusing and trapping of high-intensity laser-generated fast electrons
      at the rear of solid targets.
AB  - The transport of fast electrons generated by a 1 ps, 20 J, 10(19) W cm(-2), 1
      microm wavelength laser pulse through 70-250 microm thick deuterated polyethylene
      (CD2) targets is modeled with a Fokker-Planck hybrid code in r-z geometry.
      Initially, electric field generation inhibits propagation, which then proceeds by
      the formation of a low resistivity channel due to Ohmic heating. The magnetic
      field generated at the edge of the channel leads to strong collimation. This is
      observed for a wide range of parameters. Reflection of electrons at the rear
      surface forms a magnetic field which focuses the incident electrons on to the
      rear surface and forces the reflected electrons outwards. This would lead to the
      formation of a small diameter plasma on the rear surface, as observed in
      experiments. The reflected electrons are confined to a cone by a self-generated
      magnetic field, enhancing energy deposition at the rear of the target.

PMID- 11969588
TI  - Generation of ultrashort electron bunches by colliding laser pulses.
AB  - A proposed laser-plasma-based relativistic electron source [E. Esarey et al.,
      Phys. Rev. Lett. 79, 2682 (1997)] using laser-triggered injection of electrons is
      investigated. The source generates ultrashort electron bunches by dephasing and
      trapping background plasma electrons undergoing fluid oscillations in an excited
      plasma wake. The plasma electrons are dephased by colliding two
      counterpropagating laser pulses which generate a slow phase velocity beat wave.
      Laser pulse intensity thresholds for trapping and the optimal wake phase for
      injection are calculated. Numerical simulations of test particles, with
      prescribed plasma and laser fields, are used to verify analytic predictions and
      to study the longitudinal and transverse dynamics of the trapped plasma
      electrons. Simulations indicate that the colliding laser pulse injection scheme
      has the capability to produce relativistic femtosecond electron bunches with
      fractional energy spread of order a few percent and normalized transverse
      emittance less than 1 mm mrad using 1 TW injection laser pulses.

PMID- 11969589
TI  - Relativistic pondermotive Hamiltonian for electrons in an intense laser field.
AB  - A Hamiltonian theory of the electron drift motion in an intense laser pulse is
      presented. The action-variational Lie perturbation method is utilized to derive
      the relativistic pondermotive Hamiltonian in a rigorous and systematic way. The
      results include: the electron drift motion in a linearly polarized pulse is
      slightly anisotropic because of the finite pulse duration effects, and its drift
      in a circularly polarized pulse contains a vortex component.

PMID- 11969590
TI  - Hot, dense, millimeter-scale, high-Z plasmas for laser-plasma interactions
      studies.
AB  - We have designed and produced hot, millimeter-scale, high-Z plasmas of interest
      for National Ignition Facility hohlraum target design. Using a high-Z gas fill
      produces electron temperatures in the 3.5-6-keV range, the highest temperatures
      measured to date for high-density (10(21) e/cm(3)) laser-heated plasmas, and much
      higher than the 3 keV found for low-Z (neopentane) fills. These measurements are
      in good agreement with the target design calculations, and the L-shell
      spectroscopic approach used to estimate the electron temperature has certain
      advantages over traditional K-shell approaches.

PMID- 11969591
TI  - High-power electrostatic free-electron maser as a future source for fusion plasma
      heating: experiments in the short-pulse regime.
AB  - A high-power, frequency-tunable electrostatic free-electron maser, being
      developed at the FOM Institute for Plasma Physics "Rijnhuizen," shows lasing at
      various frequencies. An output power of 730 kW at 206 GHz is generated by a 7.2
      A, 1.77-MeV electron beam, and 380 kW at 165 GHz is generated by a 7.4-A, 1.65
      MeV electron beam. In the present experimental setup, without recovery of the
      spent electron beam power, the pulse length is limited to 12 micros.
      Nevertheless, the main issues, such as the possibility of high-power, single-mode
      operation and frequency tuning, have been confirmed. The experimental results and
      the dynamics of the laser process are well in accordance with simulations.

PMID- 11969592
TI  - Theory of modulational instability in Bragg gratings with quadratic nonlinearity.
AB  - Modulational instability in optical Bragg gratings with a quadratic nonlinearity
      is studied. The electric field in such structures consists of forward and
      backward propagating components at the fundamental frequency and its second
      harmonic. Analytic continuous wave (CW) solutions are obtained, and the intricate
      complexity of their stability, due to the large number of equations and number of
      free parameters, is revealed. The stability boundaries are rich in structures and
      often cannot be described by a simple relationship. In most cases, the CW
      solutions are unstable. However, stable regions are found in the nonlinear
      Schrodinger equation limit, and also when the grating strength for the second
      harmonic is stronger than that of the first harmonic. Stable CW solutions usually
      require a low intensity. The analysis is confirmed by directly simulating the
      governing equations. The stable regions found have possible applications in
      second-harmonic generation and dark solitons, while the unstable regions may be
      useful in the generation of ultrafast pulse trains at relatively low intensities.

PMID- 11969593
TI  - Partially coherent solitons of variable shape in a slow Kerr-like medium: exact
      solutions.
AB  - We carry out a theoretical investigation of the properties of partially coherent
      solitons for media which have a slow Kerr-like nonlinearity. We find exact
      solutions of the Nth-order Manakov equations in a general form. These describe
      partially coherent solitons (PCSs) and their collisions. In fact, the exact
      solutions allow us to analyze important properties of PCSs such as stationary
      profiles of the spatial beams and effects resulting from their collisions. In
      particular, we find, analytically, the number of parameters that control the
      soliton shape. We present profiles which are symmetric as well as those which are
      asymmetric. We also find that collisions allow the profiles to remain stationary
      but cause their shapes to change.

PMID- 11969594
TI  - Hamiltonian-versus-energy diagrams in soliton theory.
AB  - Parametric curves featuring Hamiltonian versus energy are useful in the theory of
      solitons in conservative nonintegrable systems with local nonlinearities. These
      curves can be constructed in various ways. We show here that it is possible to
      find the Hamiltonian (H) and energy (Q) for solitons of non-Kerr-law media with
      local nonlinearities without specific knowledge of the functional form of the
      soliton itself. More importantly, we show that the stability criterion for
      solitons can be formulated in terms of H and Q only. This allows us to derive all
      the essential properties of solitons based only on the concavity of the curve H
      vs Q. We give examples of these curves for various nonlinearity laws and show
      that they confirm the general principle. We also show that solitons of an
      unstable branch can transform into solitons of a stable branch by emitting small
      amplitude waves. As a result, we show that simple dynamics like the
      transformation of a soliton of an unstable branch into a soliton of a stable
      branch can also be predicted from the H-Q diagram.

PMID- 11969595
TI  - Resonant optical tunnel effect through dielectric structures of subwavelength
      cross sections.
AB  - We show that optical tunnel effects through elongated structures of subwavelength
      cross sections can be enhanced by the appropriate structuration of the local
      dielectric function. Even under total internal reflection, transfer channels can
      be excited to perform spatially confined photonic transfer between transparent
      media linked by such subwavelength structures. The optical properties of such
      systems are analyzed using field susceptibilities, also known as electromagnetic
      Green's dyadics, which determine both the local density of photon states and the
      optical transmittance of the system. Green's dyadics obtained by solving
      numerically a set of dyadic Dyson equations are applied to study the optical
      properties of subwavelength structures connecting two semi-infinite materials.

PMID- 11969596
TI  - Moving lattice kinks and pulses: an inverse method.
AB  - We develop a general mapping from given kink or pulse shaped traveling-wave
      solutions including their velocity to the equations of motion on one-dimensional
      lattices which support these solutions. We apply this mapping-by definition an
      inverse method-to acoustic solitons in chains with nonlinear intersite
      interactions, nonlinear Klein-Gordon chains, reaction-diffusion equations, and
      discrete nonlinear Schrodinger systems. Potential functions can be found in a
      unique way provided the pulse shape is reflection symmetric and pulse and kink
      shapes are at least C2 functions. For kinks we discuss the relation of our
      results to the problem of a Peierls-Nabarro potential and continuous symmetries.
      We then generalize our method to higher dimensional lattices for reaction
      diffusion systems. We find that increasing also the number of components easily
      allows for moving solutions.

PMID- 11969597
TI  - Simulation of the temporal behavior of soliton propagation in photorefractive
      media.
AB  - We consider the propagation of light beams in photorefractive media in the
      framework of a (1+1)-dimensional model. The Kukhtarev band transport model is
      introduced both in a time-dependent differential equation describing the
      evolution of the space charge field and in a nonlinear wave propagation equation.
      This latter is then numerically solved with a beam propagation method routine.
      The evolution in time and space of an initially diffracting laser beam is
      simulated as a function of initial profiles and waists. The beam is shown to go
      through a transient overfocused state prior to relaxing to a steady state
      soliton. Additional features such as the stability condition of the system or
      effects such as optical branching and soliton interactions are studied.

PMID- 11969598
TI  - Three-wave interaction solitons in optical parametric amplification.
AB  - This paper applies three-wave interaction (TWI)-soliton theory to optical
      parametric amplification when the signal, idler, and pump wave can all contain
      TWI solitons. We use an analogy between two different velocity regimes to compare
      the theory with output from an experimental synchronously pumped optical
      parametric amplifier. The theory explains the observed inability to compress the
      intermediate group-velocity wave and 20-fold pulse compression in this
      experiment. The theory and supporting numerics show that one can effectively
      control the shape and energy of the optical pulses by shifting the TWI solitons
      in the pulses.

PMID- 11969599
TI  - Bayesian inference analysis of ellipsometry data.
AB  - Variable angle spectroscopic ellipsometry is a nondestructive technique for
      accurately determining the thicknesses and refractive indices of thin films.
      Experimentally, the ellipsometry parameters psi and Delta are measured, and the
      sample structure is then determined by one of a variety of approaches, depending
      on the number of unknown variables. The ellipsometry parameters have been
      inverted analytically for only a small number of sample types. More general cases
      require either a model-based numerical technique or a series of approximations
      combined with a sound knowledge of the test sample structure. In this paper, the
      combinatorial optimization technique of simulated annealing is used to perform
      least-squares fits of ellipsometry data (both simulated and experimental) from
      both a single layer and a bilayer on a semi-infinite substrate using what is
      effectively a model-free system, in which the thickness and refractive indices of
      each layer are unknown. The ambiguity inherent in the best-fit solutions is then
      assessed using Bayesian inference. This is the only way to consistently treat
      experimental uncertainties along with prior knowledge. The Markov chain Monte
      Carlo algorithm is used. Mean values of unknown parameters and standard
      deviations are determined for each and every solution. Rutherford backscattering
      spectrometry is used to assess the accuracy of the solutions determined by these
      techniques. With our computer analysis of ellipsometry data, we find all possible
      models that adequately describe that data. We show that a bilayer consisting of a
      thin film of poly(styrene) on a thin film of silicon dioxide on a silicon
      substrate results in data that are ambiguous; there is more than one acceptable
      description of the sample that will result in the same experimental data.

PMID- 11969600
TI  - Rosenbluth chain cluster growth in the study of micelle self-assembly.
AB  - A Rosenbluth algorithm [J. Chem. Phys. 23, 356 (1955)] for enumerating clusters
      of chains is presented. The method is used to undertake a direct enumeration of
      the cluster partition function for small clusters in a three-dimensional lattice
      model of a binary mixture of amphiphile and solvent. In this model, the
      amphiphiles are represented as connected chains on a lattice, with vacant sites
      representing the solvent. The results from the Rosenbluth method are compared
      with those obtained by Metropolis Monte Carlo simulations which allow free self
      assembly of clusters. The agreement between the two methods allows an unambiguous
      identification of the packing entropy associated with micelle self-assembly.
      Results are presented for unbranched chains having two head and four tail
      segments (H2T4) and also four head and four tail segments (H4T4). Although the
      cluster enumeration method described in this paper has been developed for
      micellar systems, it will have applications in a variety of areas including
      nucleation and percolation.

PMID- 11969601
TI  - Higher-order probabilistic perceptrons as Bayesian inference engines.
AB  - An explicit structural connection is established between the Bayes optimal
      classifier operating on K binary input variables and a corresponding two-layer
      perceptron having normalized output activities and couplings from input to output
      units of all orders up to K. With suitable modification of connection weights and
      biases, such a higher-order probabilistic perceptron should in principle be able
      to learn the statistics of the classification problem and match the a posteriori
      probabilities given by Bayes optimal inference. Specific training algorithms are
      developed that allow this goal to be approximated in a controlled variational
      sense. An application to the task of discriminating between stable and unstable
      nuclides in nuclear physics yields network models with predictive performance
      comparable to the best that has been achieved with conventional multilayer
      perceptrons containing only pairwise connections.

PMID- 11969602
TI  - Avalanche and spreading exponents in systems with absorbing states.
AB  - We present generic scaling laws relating spreading critical exponents and
      avalanche exponents (in the sense of self-organized criticality) in general
      systems with absorbing states. Using these scaling laws we present a collection
      of the state-of-the-art exponents for directed percolation, dynamical
      percolation, and other universality classes. This collection of results should
      help to elucidate the connections of self-organized criticality and systems with
      absorbing states. In particular, some nonuniversality in avalanche exponents is
      predicted for systems with many absorbing states.

PMID- 11969603
TI  - Generalized Landauer equation: absorption-controlled diffusion processes.
AB  - The exact expression of the one-dimensional Boltzmann multiple-scattering
      coefficients, for the passage of particles through a slab of a given material, is
      obtained in terms of the single-scattering cross section of the material,
      including absorption. The remarkable feature of the result is that for multiple
      scattering in a metal, free from absorption, one recovers the well-known Landauer
      result for conduction electrons. In the case of particles, such as neutrons,
      moving through a weak absorbing media, Landuer's formula is modified due to the
      absorption cross section. For photons, in a strong absorbing media, one recovers
      the Lambert-Beer equation. In this latter case one may therefore speak of
      absorption-controlled diffusive processes.

PMID- 11969604
TI  - Numerical test of the damping time of layer-by-layer growth on stochastic models.
AB  - We perform Monte Carlo simulations on stochastic models such as the Wolf-Villain
      (WV) model and the Family model in a modified version to measure the mean
      separation l between islands in a submonolayer regime and the damping time t* of
      layer-by-layer growth oscillations in one dimension. The stochastic models are
      modified, allowing for diffusion within interval r upon deposition. It is found
      numerically that the mean separation and the damping time depend on the diffusion
      interval r, leading to the fact that the damping time is related to the mean
      separation as t* approximately l(4/3) for the WV model and t* approximately l(2)
      for the Family model. The numerical results are in excellent agreement with
      recent theoretical predictions.

PMID- 11969605
TI  - Temperature difference between bulk and surface transition in freely suspended
      smectic films.
AB  - We report an ellipsometric study of freely suspended films of a chiral liquid
      crystal compound possessing the phase sequence smectic-C-smectic-A-isotropic with
      a very broad (67 K) smectic-A phase range. We observe a smectic-C-smectic-A
      surface transition which is situated more than 60 K above the bulk smectic-C
      smectic-A transition temperature. Possible reasons for this unusually large
      temperature shift are discussed.

PMID- 11969606
TI  - Theory for the bending anisotropy of lipid membranes and tubule formation.
AB  - We study the spontaneous symmetry breaking of the bending rigidity of lipid
      membranes in two principal directions by a Landau mean-field theory. When the
      temperature is below the tilting temperature (T(c)), the coupling between
      molecular orientation and membrane local curvature square leads to an increase of
      the bending rigidity in the tilting direction and therefore a spontaneous
      symmetry breaking in two principal directions. The asymmetry (Delta) of the
      bending rigidity undergoes a continuous change upon cooling and grows as T(c)-T
      for T<T(c). We discuss this anisotropical effect on the tilt structure of the
      ripple phase P(beta(')) of a nearly flat membrane and the sphere-to-tubule
      transition in a dilute solution of lipids. The transition between the spherical
      vesicle phase and the tubular phase is predicted to be first order.

PMID- 11969607
TI  - Electron magnetohydrodynamic approximations and the magnetic drift wave.
AB  - It is shown that the approximations of electron magnetohydrodynamics (EMHD) are
      too restrictive to be realistic for at least plasmas of low-Z materials (for
      example, hydrogen and its isotopes). The simultaneously used assumptions of
      stationary ions and inertialess electrons are not self-consistent, especially
      within the framework of local theory. As a result the application of EMHD to
      describe the pure transverse magnetic drift wave suffers from weaknesses and such
      a mode does not seem to exist in magnetized plasmas.

PMID- 11969608
TI  - Influence of ion temperature on Lyman-alpha intensity ratios.
AB  - In this paper we examine the effects of varying ion temperature with constant
      electron temperature on the Lyman-alpha intensity ratios for a small admixture of
      hydrogenlike ions in a high-temperature plasma. We investigate the ratios with
      increasing central electron temperature, change in base plasma, and increasing
      nuclear charge, Z, of the impurity ion.

PMID- 11969609
TI  - Finite-volume lattice Boltzmann method.
AB  - We present a finite-volume formulation for the lattice Boltzmann method (FVLBM)
      based on standard bilinear quadrilateral elements in two dimensions. The accuracy
      of this scheme is demonstrated by comparing the velocity field with the
      analytical solution of the Navier-Stokes equations for time dependent rotating
      Couette flow and Taylor vortex flow. To demonstrate the flexibility of the
      scheme, we have also simulated a modified rotating Couette flow, where the inner
      cylinder has an elliptical shape. The results agree with those obtained from the
      traditional marker-and-cell method. The FVLBM scheme is applicable to arbitrarily
      shaped two-dimensional regions, and thus the range of applicability of the
      lattice Boltzmann method has been significantly extended.

PMID- 11969610
TI  - Control-parameter-dependent Swift-Hohenberg equation as a model for bioconvection
      patterns.
AB  - We consider a complex Swift-Hohenberg equation with control-parameter-dependent
      coefficients and use it as a model to describe dynamical features seen in an
      experimental bacterial bioconvection pattern. In particular, we give numerical
      results showing the development of a phase-unstable pattern behind a moving
      front.

PMID- 11969611
TI  - Effects of quenched disorder in the two-dimensional Potts model: a Monte Carlo
      study.
AB  - Motivated by recent experiments on phase behavior of systems confined in porous
      media, we have studied the effect of randomness on the nature of the phase
      transition in the two-dimensional Potts model. To model the effects of the porous
      matrix we introduce a random distribution of couplings P(J(ij))=pdelta(J(ij)
      J1)+(1-p)delta(J(ij)-J2) in the q state Potts Hamiltonian. An extensive Monte
      Carlo study is made on this system for q=5. We studied two different cases of
      disorder (a) J(1)/J(2)-->infinity and p=0.8 and (b) J(1)/J(2)=10 and p=0.5. We
      observed, in both cases, that the weak first order transition that appears in the
      pure case, changes to a second-order transition. A finite size scaling analysis
      shows that the correlation length exponent nu is close to 1 and the best fit to
      the dependence of the specific heat on system size is logarithmic. This suggests
      that both cases belong to the universality class of the Ising model. In contrast,
      the magnetic exponents point to a different universality class.

PMID- 11969613
TI  - Spin of Dirac's relativistic membrane.
AB  - The Hamiltonian of Dirac's relativistic membrane is linearized by means of a
      gauge transformation. It is pointed out that the membrane spin is +/- (planck)/2.
      Furthermore, in a quantum relativistic framework neutrinolike particles are
      obtained when the membrane charge vanishes.

PMID- 11969612
TI  - Some consequences of exchangeability in random-matrix theory.
AB  - Properties of infinite sequences of exchangeable random variables result directly
      in explicit expressions for calculating asymptotic densities of eigenvalues
      rho(infinity)(lambda) of any ensemble of random matrices H whose distribution
      depends only on tr(H+H), where H+ is the Hermitian conjugate of H. For real
      symmetric matrices and for Hermitian matrices, the densities
      rho(infinity)(lambda) are constructed by summing up Wigner semicircles with
      varying radii and weights as confirmed by Monte Carlo simulations. Extensions to
      more general matrix ensembles are also considered.

PMID- 11969614
TI  - Surface restructuring, kinetic oscillations, and chaos in heterogeneous catalytic
      reactions.
AB  - We present comprehensive Monte Carlo simulations of isothermal kinetic
      oscillations and chaos in catalytic reactions accompanied by adsorbate-induced
      surface restructuring. Our analysis is based on the lattice-gas model describing
      surface restructuring in terms of the statistical theory of first-order phase
      transitions. As an example, we treat the kinetics of the NO-H2 reaction on the
      Pt(100) surface. A proposed reduced mechanism of this reaction includes NO
      adsorption, desorption, and decomposition occurring on the restructured patches
      of the surface (the decomposition products are rapidly removed from the surface
      via N2 desorption and H2O formation and desorption). Calculations are performed
      with a qualitatively realistic ratio between the rates of different elementary
      steps. In particular, NO diffusion is several orders of magnitude faster compared
      to the other steps. On the nm scale, the model predicts formation of restructured
      islands with atomically sharp boundaries. The shape of the islands is found to
      change dramatically with varying reaction conditions. Despite phase separation on
      the surface, the transition from almost harmonic oscillations (with relatively
      small separate islands) to chaos (with merging islands) is demonstrated to occur
      via the standard Feigenbaum scenario. Near the critical point, the dependence of
      the amplitude of oscillations on the governing parameter is shown to be close to
      that predicted for the Hopf supercritical bifurcation.

PMID- 11969615
TI  - Nature of transitions in augmented discrete nonlinear Schrodinger equations.
AB  - We investigate the nature of the transitions between free and self-trapping
      states occurring in systems described by augmented forms of the discrete
      nonlinear Schrodinger equation. These arise from an interaction between a moving
      quasiparticle (such as an electron or an exciton) and lattice vibrations, when
      the effects of nonlinearities in interaction potential and restoring force are
      included. We derive analytic conditions for the stability of the free state and
      the crossover between first- and second-order transitions. We demonstrate our
      results for different types of nonlinearities in the interaction potential and
      restoring force. We find that, depending on the type of nonlinearity, it is
      possible to have both first- and second-order transitions. We discuss possible
      hysteresis effects.

PMID- 11969617
TI  - Macroscopic dynamics of multilane traffic.
AB  - We present a macroscopic model of mixed multilane freeway traffic that can be
      easily calibrated to empirical traffic data, as is shown for Dutch highway data.
      The model is derived from a gas-kinetic level of description, including effects
      of vehicular space requirements and velocity correlations between successive
      vehicles. We also give a derivation of the lane-changing rates. The resulting
      dynamic velocity equations contain nonlocal and anisotropic interaction terms
      which allow a robust and efficient numerical simulation of multilane traffic. As
      demonstrated by various examples, this facilitates the investigation of
      synchronization patterns among lanes and effects of on ramps, off ramps, lane
      closures, or accidents.

PMID- 11969616
TI  - Equation of states for classical Coulomb systems: use of the Hubbard-Schofield
      approach.
AB  - An effective method based on the Hubbard-Schofield approach [Phys. Lett. A 40,
      245 (1972)] is developed to calculate the free energy of classical Coulomb
      systems. This method significantly simplifies the derivation of the cluster
      expansion. A diagrammatic representation of the cluster integrals is proposed.
      Simple rules providing the leading order in density n of each diagrammatic
      contribution are found. We calculate the n(3) contribution and recover the
      results at the order n(5/2) obtained by the traditional method of resummation of
      diverging Mayer bonds.

PMID- 11969618
TI  - Dynamical regimes in the dissipative particle dynamics model.
AB  - We discuss theoretically the behavior of the velocity autocorrelation function in
      the dissipative particle dynamics (DPD) model. Two dynamical regimes are
      identified depending on the dimensionless model parameters. For low values of the
      dimensional friction, a mean field behavior is observed in which the kinetic
      theory for the DPD model provides good predictions. For high values of the
      friction, collective hydrodynamic effects are dominant. We have performed
      numerical simulations that validate the theory presented.

PMID- 11969619
TI  - Solution of lattice gas models in the generalized ensemble on the Bethe lattice.
AB  - We present the exact Bethe lattice solution for a lattice gas Potts model defined
      in the generalized ensemble which was previously studied in elucidating the
      anomalous thermodynamic properties of water. For this model the locus of density
      maxima (TMD), the locus of isothermal compressibility extrema, (TEC), the
      spinodal curve, and the percolation curve for four hydrogen bonded molecules are
      calculated using the Bethe lattice solution. The results confirm qualitative
      relationships between the TMD, the TEC, and the percolation curve obtained
      previously from a mean field calculation.

PMID- 11969620
TI  - Exactly solvable sandpile with fractal avalanching.
AB  - A simple one-dimensional sandpile model is constructed which possesses exact
      analytical solvability while displaying both scale-free behavior and fractal
      properties. The sandpile grows by avalanching on all scales, yet its shape and
      energy content are described by a simple, continuous (but nowhere differentiable)
      analytical formula. The avalanche energy distribution and the avalanche time
      series are both power laws with index -1 ("1/f spectra").

PMID- 11969621
TI  - Theory of the NO+CO surface-reaction model.
AB  - We derive a pair approximation (PA) for the NO+CO model with instantaneous
      reactions. For both the triangular and square lattices, the PA, derived here
      using a simpler approach, yields a phase diagram with an active state for CO
      fractions y in the interval y(1)<y<y(2), with a continuous (discontinuous) phase
      transition to a poisoned state at y(1) (y(2)). This is in qualitative agreement
      with simulation for the triangular lattice, where our theory gives a rather
      accurate prediction for y(2). To obtain the correct phase diagram for the square
      lattice, i.e., no active stationary state, we reformulate the PA using
      sublattices. The (formerly) active regime is then replaced by a poisoned state
      with broken symmetry (unequal sublattice coverages), as observed recently by
      Kortluke et al. [Chem. Phys. Lett. 275, 85 (1997)]. In contrast with their
      approach, in which the active state persists, although reduced in extent, we
      report here the qualitatively correct theory of the NO+CO model on the square
      lattice. Surface diffusion of nitrogen can lead to an active state in this case.
      In one dimension, the PA predicts that diffusion is required for the existence of
      an active state.

PMID- 11969622
TI  - Entropy of classical histories.
AB  - We consider a number of proposals for the entropy of sets of classical coarse
      grained histories based on the procedures of Jaynes, and we prove a series of
      inequalities relating these measures. We then examine these as a function of the
      coarse-graining for various classical systems, and show explicitly that the
      entropy is minimized by the finest-grained description of a set of histories. We
      propose an extension of the second law of thermodynamics to the entropy of
      histories. We briefly discuss the implications for decoherent or consistent
      history formulations of quantum mechanics.

PMID- 11969623
TI  - Nonequilibrium critical behavior in unidirectionally coupled stochastic
      processes.
AB  - Phase transitions from an active into an absorbing, inactive state are
      generically described by the critical exponents of directed percolation (DP),
      with upper critical dimension d(c)=4. In the framework of single-species reaction
      diffusion systems, this universality class is realized by the combined processes
      A-->A+A, A+A-->A, and A-->0. We study a hierarchy of such DP processes for
      particle species A,B,..., unidirectionally coupled via the reactions A-->B,
      ...(with rates mu(AB),...). When the DP critical points at all levels coincide,
      multicritical behavior emerges, with density exponents beta(i) which are markedly
      reduced at each hierarchy level i> or =2. This scenario can be understood on the
      basis of the mean-field rate equations, which yield beta(i)=1/2(i-1) at the
      multicritical point. Using field-theoretic renormalization-group techniques in
      d=4-epsilon dimensions, we identify a new crossover exponent phi, and compute
      phi=1+O(epsilon(2)) in the multicritical regime (for small mu(AB)) of the second
      hierarchy level. In the active phase, we calculate the fluctuation correction to
      the density exponent on the second hierarchy level, beta(2)=1/2
      epsilon/8+O(epsilon(2)). Outside the multicritical region, we discuss the
      crossover to ordinary DP behavior, with the density exponent beta(1)=1
      epsilon/6+O(epsilon(2)). Monte Carlo simulations are then employed to confirm the
      crossover scenario, and to determine the values for the new scaling exponents in
      dimensions d< or =3, including the critical initial slip exponent. Our theory is
      connected to specific classes of growth processes and to certain cellular
      automata, and the above ideas are also applied to unidirectionally coupled pair
      annihilation processes. We also discuss some technical as well as conceptual
      problems of the loop expansion, and suggest some possible interpretations of
      these difficulties.

PMID- 11969624
TI  - Precursor phenomena in frustrated systems.
AB  - To understand the origin of the dynamical transition, between high-temperature
      exponential relaxation and low-temperature nonexponential relaxation, that occurs
      well above the static transition in glassy systems, a frustrated spin model, with
      and without disorder, is considered. The model has two phase transitions, the
      lower being a standard spin glass transition (in the presence of disorder) or
      fully frustrated Ising (in the absence of disorder), and the higher being a Potts
      transition. Monte Carlo results clarify that in the model with (or without)
      disorder the precursor phenomena are related to the Griffiths (or Potts)
      transition. The Griffiths transition is a vanishing transition which occurs above
      the Potts transition and is present only when disorder is present, while the
      Potts transition which signals the effect due to frustration is always present.
      These results suggest that precursor phenomena in frustrated systems are due
      either to disorder and/or to frustration, giving a consistent interpretation also
      for the limiting cases of Ising spin glass and of Ising fully frustrated model,
      where also the Potts transition is vanishing. This interpretation could play a
      relevant role in glassy systems beyond the spin systems case.

PMID- 11969625
TI  - Residence time distribution for a class of Gaussian Markov processes.
AB  - We study the distribution of residence time or equivalently that of "mean
      magnetization" for a family of Gaussian Markov processes indexed by a positive
      parameter alpha. The persistence exponent for these processes is simply given by
      theta=alpha but the residence time distribution is nontrivial. The shape of this
      distribution undergoes a qualitative change as theta increases, indicating a
      sharp change in the ergodic properties of the process. We develop two alternate
      methods to calculate exactly but recursively the moments of the distribution for
      arbitrary alpha. For some special values of alpha, we obtain closed form
      expressions of the distribution function.

PMID- 11969626
TI  - Emergence of cooperation among interacting individuals.
AB  - We study the evolution of interacting individuals located on the sites of a
      regular lattice. The individuals play a two action game in which the players
      either cooperate or defect with respect to a certain issue. The main rule of the
      game is that a player does not change his action when he and his opponent have
      held the same action in the previous round. Numerical simulations performed on a
      square lattice show a stationary state in which the lattice has a finite number
      of cooperators and defectors and two frozen states, one full of cooperators and
      the other full of defectors.

PMID- 11969627
TI  - Intrawell relaxation of overdamped Brownian particles.
AB  - We consider an overdamped Brownian particle in a well. When the particle escapes,
      it does so as an instanton, i.e., in one run and without dwelling anywhere on the
      way from the bottom of the well to the top of the barrier. For a sufficiently
      steep slope the instanton time equals the time it takes the particle to
      deterministically slide down the same slope. We show that the instanton time is
      also the relaxation time for the escape rate after the barrier changes shape.

PMID- 11969628
TI  - Non-Hermitian localization and delocalization.
AB  - We study localization and delocalization in a class of non-Hermitian Hamiltonians
      inspired by the problem of vortex pinning in superconductors. In various
      simplified models we are able to obtain analytic descriptions, in particular, of
      the nonperturbative emergence of a forked structure (the appearance of "wings")
      in the density of states. We calculate how the localization length diverges at
      the localization-delocalization transition. We map some versions of this problem
      onto a random walker problem in two dimensions. For a certain model, we find an
      intricate structure in its density of states.

PMID- 11969629
TI  - Semianalytic solution of the Kramers exit problem for a small ferromagnetic
      particle.
AB  - The distribution Q(t) of magnetization reversal times in a small uniaxial
      particle is computed here directly from Brown's Fokker-Planck equation. Constant
      applied field and axial symmetry are assumed. The Laplace transform of Q(t) has
      the form Q(z)=F(1)(z)/F(2)(z) where the regular functions F(i)(z) are defined by
      a solution of a Volterra integral equation. A separate integral equation is
      derived for the function dF(2)(z)/dz, and the poles and residues of Q(z) may then
      be found numerically with arbitary precision.

PMID- 11969630
TI  - Feynman's ratchet and pawl: an exactly solvable model.
AB  - We introduce a simple, discrete model of Feynman's ratchet and pawl, operating
      between two heat reservoirs. We solve exactly for the steady-state directed
      motion and heat flows produced, first in the absence and then in the presence of
      an external load. We show that the model can act both as a heat engine and as a
      refrigerator. We finally investigate the behavior of the system near equilibrium,
      and use our model to confirm general predictions based on linear-response theory.

PMID- 11969632
TI  - Large deviation function of the partially asymmetric exclusion process.
AB  - The large deviation function obtained recently by Derrida and Lebowitz [Phys.
      Rev. Lett. 80, 209 (1998)] for the totally asymmetric exclusion process is
      generalized to the partially asymmetric case in the scaling limit. The asymmetry
      parameter rescales the scaling variable in a simple way. The finite-size
      corrections to the universal scaling function and the universal cumulant ratio
      are also obtained to the leading order.

PMID- 11969631
TI  - Scale invariant dynamics of surface growth.
AB  - We describe in detail and extend a recently introduced nonperturbative
      renormalization group (RG) method for surface growth. The scale invariant
      dynamics which is the key ingredient of the calculation is obtained as the fixed
      point of a RG transformation relating the representation of the microscopic
      process at two different coarse-grained scales. We review the RG calculation for
      systems in the Kardar-Parisi-Zhang (KPZ) universality class and compute the
      roughness exponent for the strong coupling phase in dimensions from 1 to 9.
      Discussions of the approximations involved and possible improvements are also
      presented. Moreover, very strong evidence of the absence of a finite upper
      critical dimension for KPZ growth is presented. Finally, we apply the method to
      the linear Edwards-Wilkinson dynamics where we reproduce the known exact results,
      proving the ability of the method to capture qualitatively different behaviors.

PMID- 11969633
TI  - Nucleation theorems applied to the Ising model.
AB  - We use Monte Carlo simulations to study a single cluster of "up" spins in a sea
      of "down" spins in the three-dimensional Ising model. We evaluate the growth and
      decay rates for clusters of different sizes, identify the critical size for which
      these rates are equal, and obtain the internal energy of the critical size
      cluster. The results of the simulations at different temperatures and magnetic
      fields are used together with the first and second nucleation theorems to predict
      how the cluster nucleation rate changes when the external magnetic field and the
      temperature are changed. Our results are in agreement with literature values, but
      our method requires significantly less computational effort than the simulations
      reported earlier and avoids the difficult evaluation of free energies.

PMID- 11969634
TI  - Exact phase diagrams for an Ising model on a two-layer Bethe lattice.
AB  - Using an iteration technique, we obtain exact expressions for the free energy and
      the magnetization of an Ising model on a two-layer Bethe lattice with intralayer
      coupling constants J1 and J2 for the first and the second layer, respectively,
      and interlayer coupling constant J3 between the two layers; the Ising spins also
      couple with external magnetic fields, which are different in the two layers. We
      obtain exact phase diagrams for the system and find that when /J3/-->0, DeltaT(c)
      identical with[T(c)(J3)-T(c)(0)]/T(c)(0) approximately [J3]/J(1)/(1/psi), where
      T(c)(J3) is the phase-transition temperature for the system with interlayer
      coupling constant J3 and the shift exponent psi is 1 for J(1)=J(2) and is 0.5 for
      J1 not equal to J2. Such results are consistent with predictions of a scaling
      theory. We also derive equations for DeltaT(c) when /J3/ approaches infinity.

PMID- 11969635
TI  - Slow algebraic relaxation in quartic potentials and related results.
AB  - We present a detailed report [see S. Sen et al., Phys. Rev. Lett. 77, 4855
      (1996)] of our numerical and analytical studies on the relaxation of a classical
      particle in the potentials V(x)= +/-x(2)/2+x(4)/4. Both of the approaches confirm
      that at all temperatures, the relaxation functions (e.g., velocity relaxation
      function and position relaxation function) decay asymptotically in time t as
      sin(omega(0)t)/t. Numerically calculated power spectra of the relaxation
      functions show a gradual transition with increasing temperature from a single
      sharp peak located at the harmonic frequency omega(0) to a broad continuous band.
      The 1/t relaxation is also found when V(x) is a polynomial in powers of x(2) with
      a nonvanishing coefficient accompanying the x(4) term in V(x). Numerical
      calculations show that in the cases in which the leading term in V(x) behaves as
      x(2n) with integer n, the asymptotic relaxation exhibits 1/t(phi) decay where phi
      =1/(n-1). We briefly discuss the analytical approaches to relaxation studies in
      these strongly anharmonic systems using direct solution of the equation of motion
      and using the continued fraction formalism approach for relaxation studies. We
      show that the study of the dynamics of strongly anharmonic oscillators poses
      unique difficulties when studied via the continued fraction or any other time
      series construction based approaches. We close with comments on the physical
      processes in which the insights presented in this work may be applicable.

PMID- 11969636
TI  - Critical behavior of a random diode network.
AB  - We study the percolation properties of a random diode network (RDN) which
      contains two kinds of directed bonds on a square lattice. This network is a
      special case of the random insulation-resistor-diode network. Both Monte Carlo
      simulations and series expansion for the percolation probability show that an
      estimated critical exponent, beta=0.1794+/-0.008, is different from known values
      for a conventional insulation-resistor-diode network. RDN belongs to neither the
      isotropic percolation universality class nor to the directed percolation
      universality, which we attribute to a difference of symmetry breakdown around the
      critical point.

PMID- 11969638
TI  - Signal and background separation.
AB  - In many areas of research the measured spectra consist of a collection of "peaks"
      -the sought-for signals--which sit on top of an unknown background. The
      subtraction of the background in a spectrum has been the subject of many
      investigations and different techniques, varying from filtering to fitting
      polynomial functions, have been developed. These techniques yield results that
      are not always satisfactory and often even misleading. Based upon the rules of
      probability theory, we derive a formalism to separate the background from the
      signal part of a spectrum in a rigorous and self-consistent manner. We compare
      the results of the probabilistic approach to those obtained by two commonly used
      methods in an analysis of particle induced x-ray emission spectra.

PMID- 11969637
TI  - Persistent random walk model for transport through thin slabs.
AB  - We present a model for transport in multiply scattering media based on a three
      dimensional generalization of the persistent random walk. The model assumes that
      photons move along directions that are parallel to the axes. Although this
      hypothesis is not realistic, it allows us to solve exactly the problem of
      multiple scattering propagation in a thin slab. Among other quantities, the
      transmission probability and the mean transmission time can be calculated
      exactly. Besides being completely solvable, the model could be used as a
      benchmark for approximation schemes to multiple light scattering.

PMID- 11969639
TI  - Nonlinear Langevin equations and the time dependent density functional method.
AB  - To study the time dependent density functional method (TDDFM), two streaming
      velocity (reversible) terms are reformulated in the nonlinear Langevin equation.
      Mori's [Prog. Theor. Phys. 33, 423 (1965)] projection operator method shows a
      variety of nonlinear Langevin equations. This is because the equations depend on
      the choice of phase space functions employed in the projection. If phase space
      functions include particular functions, however, the streaming velocity term has
      an invariable form. The form is independent of the choice of other phase space
      functions. Since the invariable streaming velocity term does not introduce the
      TDDFM, the second viewpoint is presented. In this, the linearization of the
      streaming velocity term agrees with the frequency term in the linear Langevin
      equation. Since only the second streaming velocity term introduces the TDDFM, one
      needs to be cautious in the derivation of the TDDFM.

PMID- 11969640
TI  - Spectral correlations in systems undergoing a transition from periodicity to
      disorder.
AB  - We study the spectral statistics for extended yet finite quasi-one-dimensional
      systems, which undergo a transition from periodicity to disorder. In particular,
      we compute the spectral two-point form factor, and the resulting expression
      depends on the degree of disorder. It interpolates smoothly between the two
      extreme limits-the approach to Poissonian statistics in the (weakly) disordered
      case, and the universal expressions derived in T. Dittrich, B. Mehlig, H. Schanz,
      and U. Smilansky, Chaos Solitons Fractals 8, 1205 (1997); Phys. Rev. E 57, 359
      (1998); B. D. Simons and B. L. Altshuler, Phys. Rev. Lett. 70, 4063 (1993); and
      N. Taniguchi and B. L. Altshuler, ibid. 71, 4031 (1993) for the periodic case.
      The theoretical results agree very well with the spectral statistics obtained
      numerically for chains of chaotic billiards and graphs.

PMID- 11969641
TI  - Relationships among coefficients in deterministic and stochastic transient
      diffusion.
AB  - Systems are studied in which transport is possible due to large extensions with
      open boundaries in certain directions, but the particles responsible for
      transport can disappear from it by leaving it in other directions, by chemical
      reaction or by adsorption. The connection of the total escape rate, the rate of
      the disappearance, and the diffusion coefficient is investigated. It leads to the
      observation that the diffusion coefficient defined by <x(2)> is in general
      different from the one present in the effective Fokker-Planck equation. The
      result makes it possible to generalize the Gaspard-Nicolis formula [Phys. Rev.
      Lett. 65, 1693 (1990)] to this transient case in deterministic systems.

PMID- 11969642
TI  - Bifurcations and chaos in a parametrically damped two-well Duffing oscillator
      subjected to symmetric periodic pulses.
AB  - We study a parametrically damped two-well Duffing oscillator, subjected to a
      periodic string of symmetric pulses. The order-chaos threshold when altering
      solely the width of the pulses is investigated theoretically through Melnikov
      analysis. We show analytically and numerically that most of the results appear
      independent of the particular wave form of the pulses provided that the
      transmitted impulse is the same. By using this property, the stability boundaries
      of the stationary solutions are determined to first approximation by means of an
      elliptic harmonic balance method. Finally, the bifurcation behavior at the
      stability boundaries is determined numerically.

PMID- 11969643
TI  - Wavelet-based fractal analysis of airborne pollen.
AB  - The most abundant biological particles in the atmosphere are pollen grains and
      spores. Self-protection of a pollen allergy is possible through information about
      future pollen contents in the air. In spite of the importance of airborne pollen
      concentration forecasting, it has not been possible to predict the pollen
      concentrations with great accuracy, and about 25% of daily pollen forecasts
      result in failures. Previous analyses of the dynamic characteristics of
      atmospheric pollen time series indicate that the system can be described by a low
      dimensional chaotic map. We apply a wavelet transform to study the multifractal
      characteristics of an airborne pollen time series. The information and the
      correlation dimensions correspond to a chaotic system showing a loss of
      information with time evolution.

PMID- 11969644
TI  - Controlling and synchronizing space time chaos.
AB  - Control and synchronization of continuous space-extended systems is realized by
      means of a finite number of local tiny perturbations. The perturbations are
      selected by an adaptive technique, and they are able to restore each of the
      independent unstable patterns present within a space time chaotic regime, as well
      as to synchronize two space time chaotic states. The effectiveness of the method
      and the robustness against external noise is demonstrated for the amplitude and
      phase turbulent regimes of the one-dimensional complex Ginzburg-Landau equation.
      The problem of the minimum number of local perturbations necessary to achieve
      control is discussed as compared with the number of independent spatial
      correlation lengths.

PMID- 11969645
TI  - Influence of phase-space localization on the energy diffusion in a quantum
      chaotic billiard.
AB  - The quantum dynamics of a chaotic billiard with moving boundary is considered in
      this paper. We found a shape parameter Hamiltonian expansion, which enables us to
      obtain the spectrum of the deformed billiard for deformations so large as the
      characteristic wavelength. Then, for a specified time-dependent shape variation,
      the quantum dynamics of a particle inside the billiard is integrated directly. In
      particular, the dispersion of the energy is studied in the Bunimovich stadium
      billiard with oscillating boundary. The results showed that the distribution of
      energy spreads diffusively for the first oscillations of the boundary
      (<Delta2E>=2Dt). We studied the diffusion constant D as a function of the
      boundary velocity and found differences with theoretical predictions based on
      random matrix theory. By extracting highly phase-space localized structures from
      the spectrum, previous differences were reduced significantly. This fact provides
      numerical evidence of the influence of phase-space localization on the quantum
      diffusion of a chaotic system.

PMID- 11969646
TI  - Bicritical behavior of period doublings in unidirectionally coupled maps.
AB  - We study the scaling behavior of period doublings in two unidirectionally coupled
      one-dimensional maps near a bicritical point where two critical lines of period
      doubling transition to chaos in both subsystems meet. Note that the bicritical
      point corresponds to a border of chaos in both subsystems. For this bicritical
      case, the second response subsystem exhibits a type of non-Feigenbaum critical
      behavior, while the first drive subsystem is in the Feigenbaum critical state.
      Using two different methods, we make the renormalization-group analysis of the
      bicritical behavior and find the corresponding fixed point of the renormalization
      transformation with two relevant eigenvalues. The scaling factors obtained by the
      renormalization-group analysis agree well with those obtained by a direct
      numerical method.

PMID- 11969647
TI  - Recovering smooth dynamics from time series with the aid of recurrence plots.
AB  - A graphical method based on recurrence plots is used in the reconstruction of the
      phase space from a time series of measurements. It is demonstrated that if the
      embedding delay and dimension are correctly chosen, the recurrence plot of a
      smooth dynamical system has a particularly simple form. It is shown how to use
      recurrence plots to determine the correct embedding parameters so that reliable
      quantitative information can be drawn about the system generating the time
      series. The average line length in the plot is shown to be directly related to
      the prediction horizon. Furthermore, it is a numerical characteristic of the
      embedded series independent of the threshold used in the plot.

PMID- 11969648
TI  - Magnetic effect for electrochemically driven cellular convection.
AB  - Hydrodynamic instability analogous to Rayleigh-Benard convection is observed in
      an electrolytic solution between two parallel copper wire electrodes. The laser
      interferometric technique can reveal the dissipation structure created by the
      motion of the fluid, which is controlled electrochemically. It is shown that
      under the presence of horizontal magnetic field the roll cells move horizontally
      along the electrodes. The electrochemically driven convection is simply
      controlled and monitored by setting and measuring the electrochemical parameters
      and forms many kinds of spatiotemporal patterns, especially under the magnetic
      field. The phenomenon is modeled by considering a Boussinesq fluid under a
      concentration gradient. The stability of the resulting equations is studied by
      linear stability analysis. The time dependent nonlinear system is investigated
      numerically and the main features of the experimental response are reproduced.

PMID- 11969649
TI  - Measuring scars of periodic orbits.
AB  - The phenomenon of periodic orbit scarring of eigenstates of classically chaotic
      systems is attracting increasing attention. Scarring is one of the most important
      "corrections" to the ideal random eigenstates suggested by random matrix theory.
      This paper discusses measures of scars and in so doing also tries to clarify the
      concepts and effects of eigenfunction scarring. We propose a universal scar
      measure which takes into account an entire periodic orbit and the linearized
      dynamics in its vicinity. This measure is tuned to pick out those structures
      which are induced in quantum eigenstates by unstable periodic orbits and their
      manifolds. It gives enhanced scarring strength as measured by eigenstate overlaps
      and inverse participation ratios, especially for longer orbits. We also discuss
      off-resonance scars which appear naturally on either side of an unstable periodic
      orbit.

PMID- 11969650
TI  - Decoding information by following parameter modulation with parameter adaptive
      control.
AB  - It has been proposed to realize secure communication using chaotic
      synchronization via transmission of a binary message encoded by parameter
      modulation in the chaotic system. This paper considers the use of parameter
      adaptive control techniques to extract the message, based on the assumptions that
      we know the equation form of the chaotic system in the transmitter but do not
      have access to the precise values of the parameters which are kept secret as a
      secure set. In the case in which a synchronizing system can be constructed using
      parameter adaptive control by the transmitted signal and the synchronization is
      robust to parameter mismatches, the parameter modulation can be revealed and the
      message decoded without resorting to exact parameter values in the secure set. A
      practical local Lyapunov function method for designing parameter adaptive control
      rules based on originally synchronized systems is presented.

PMID- 11969651
TI  - Theory of circle maps and the problem of one-dimensional optical resonator with a
      periodically moving wall.
AB  - We consider the electromagnetic field in a cavity with a periodically oscillating
      perfectly reflecting boundary and show that the mathematical theory of circle
      maps leads to several physical predictions. Notably, well-known results in the
      theory of circle maps (which we review briefly) imply that there are intervals of
      parameters where the waves in the cavity get concentrated in wave packets whose
      energy grows exponentially. Even if these intervals are dense for typical motions
      of the reflecting boundary, in the complement there is a positive measure set of
      parameters where the energy remains bounded.

PMID- 11969652
TI  - Streaminglike diffusion in the low-dimensional stochastic pump model.
AB  - In this paper we analyze a diffusion phenomenon in a few-dimensional Hamiltonian
      system of coupled mappings in which the principal component of diffusion occurs
      along resonances. The result is that the diffusion can have power-law dependence
      in coupling parameter mu and be independent of the stochastic parameter K. For
      the same range of parameters, the usual analytical Arnold diffusion across
      resonances is dependent on K and can be much smaller than resonance streaming
      diffusion. The results are used to qualitatively explain recent results in
      multidimensional coupled standard maps.

PMID- 11969653
TI  - Bi-instability as a precursor to global mixed-mode chaos.
AB  - Bi-instability, in contrast to bistability, is shown to generate unstable chaotic
      saddles prior to the onset of chaos. The theory and numerics are applied to a CO2
      laser model with modulated losses where unstable pairs of saddles coexist, form
      heteroclinic connections, and allow mixing between local chaotic attractors to
      produce global mixed-mode chaos.

PMID- 11969654
TI  - Investigating one-dimensional diffusion by quasielastic neutron scattering: a
      theoretical approach.
AB  - Scattering functions and full widths at half maximum for quasielastic neutron
      scattering (QENS) are calculated for diffusion in systems of one-dimensional
      channels. The self-correlation function for diffusion in isotropically oriented
      channels is given and it is found that this function diverges at the origin. The
      calculations are carried out for both normal and single-file diffusion and the
      influence of the ballistic phase is investigated. It is found that the ballistic
      phase influences the scattering functions very strongly for large diffusion
      coefficients. QENS data from the literature are analyzed with respect to this
      influence. The influence of three different resolution functions (triangular,
      Gaussian, and Lorentzian) is considered.

PMID- 11969655
TI  - Combined action of different mechanisms of convective instability in multilayer
      systems.
AB  - The nonlinear regimes of convection in a system of three immiscible viscous
      fluids are investigated by the finite-difference method. We study new phenomena
      caused by direct and indirect interaction of thermocapillary and buoyancy
      (Rayleigh and anticonvective) instability mechanisms. Two variants of heating
      from below and from above-are considered. The interfaces are assumed to be flat.
      We focus on nonlinear evolution of steady and oscillatory motions and selection
      of stable convective structures depending on the parameters of systems. The
      influence of the lateral boundary conditions is also investigated. A
      classification of different variants of interaction between Rayleigh and
      thermocapillary instability mechanisms is presented, and several typical examples
      are studied. Specifically, we considered six different configurations where the
      Rayleigh convection arises mainly in a definite layer, and the thermocapillary
      convection appears mainly near the definite interface. Also, the case where both
      interfaces are active and alternatively play a dominant role is investigated.
      Some configurations of interaction between anticonvective and thermocapillary
      instability mechanisms are considered.

PMID- 11969656
TI  - Determination of the quench velocity and rewetting temperature of hot surfaces:
      Formulation of a nonisothermal microscale hydrodynamic model.
AB  - A nonisothermal microscale model of the three-phase, solid-liquid-gas, contact
      zone is formulated in the context of rewetting phenomena. The model incorporates
      hydrodynamics, heat transfer, interfacial phenomena, and intermolecular long
      range forces, in a two-dimensional proximal region of the order of 1000 A in
      width and 100 A in thickness. The model comprises scaled mass, momentum, and
      energy balances, and their corresponding scaled boundary conditions. The small
      contact angles which are characteristic of rewetting situations facilitate the
      use of the lubrication approximation, and the dynamics of the liquid and gas
      phases is decoupled by applying the one-sided simplification. The microscale
      hydrodynamic model reflects the strong effect of the solid-liquid interactions on
      the film profile, and the attendant flow and thermal fields. Thinner films having
      smaller contact angles involve stronger solid-liquid attraction forces, and
      consequently they exhibit higher rewetting temperatures and lower evaporation and
      vapor recoil effects. Thermocapillary and evaporation and conduction effects are
      expressed by appropriate dimensionless numbers. A set of such numbers is defined
      in the context of the differential equations of the microscale model. This model
      covers the hydrodynamic aspect of rewetting phenomena, which are also controlled
      by thermodynamic and macroscale constraints. This calls for interfacing and
      appropriate combination between the microscale hydrodynamic model,
      thermodynamics, and other macroscale rewetting models, for the determination of
      rewetting temperatures and quench velocities of liquids on hot solid surfaces.
      This is addressed elsewhere, in subsequent papers that follow this work.

PMID- 11969657
TI  - Spreading dynamics of terraced droplets.
AB  - The liquid crystal (-)7S5 spreads as a two-terraced droplet on an oxide covered
      (100) Si wafer. The thickness of the upper and lower terraces are respectively
      approximately 200 and approximately 40 A. This is the simplest system for which
      the de Gennes and Cazabat (dGC) terraced spreading model [C. R. Acad. Sci. II
      310, 1601 (1990)] is applicable. We find that soon after the upper terrace
      acquires a flat top a hole develops in the center of this terrace. The hole
      propagates down to the depth of the first terrace. In this contribution we
      demonstrate that the dGC model is unstable to the formation of a hole in the
      center of the upper terrace for a two-terraced droplet. Our extended dGC model,
      which includes a hole in the upper terrace, provides a reasonable description of
      the average spreading dynamics for this system. However, this model has
      difficulties quantitatively accounting for all of the features exhibited by the
      dynamics, perhaps because experimentally the inner and outer borders of the upper
      terrace become irregular with time. These irregularities in the borders have not
      been included within the model.

PMID- 11969658
TI  - Model for single-particle dynamics in supercooled water.
AB  - We analyze a set of 10 M-step molecular dynamics (MD) data of low-temperature
      SPC/E model water with a phenomenological analytical model. The motivation is
      twofold: to extract various k-dependent physical parameters associated with the
      single-particle or the self-intermediate scattering functions (SISFs) of water at
      a deeply supercooled temperature and to apply this analytical model to analyses
      of new high resolution quasielastic neutron scattering data presented elsewhere.
      The SISF of the center of mass computed from the MD data show clearly time
      separated two-step relaxations with a well defined plateau in between. We model
      the short time relaxation of the test particle as a particle trapped in a
      harmonical potential well with the vibrational frequency distribution function
      having a two-peak structure known from previous inelastic neutron scattering
      experiments. For the long time part of the relaxation, we take the alpha
      relaxation suggested by mode-coupling theory. The model fits the low-temperature
      SISF over the entire time range from 1 fs to 10 ns, allowing us to extract peak
      positions of the vibrational density of states, the structural relaxation rate
      1/tau of the cage (the potential well) and the stretch exponent beta. The
      structural relaxation rate has a power law dependence on the magnitude of the
      wave vector transfer k and the stretch exponent varies from 0.55 at large k to
      unity at small k.

PMID- 11969659
TI  - Analysis of energy cascade models of turbulence.
AB  - The exponent tau(p) that describes the scaling of the order-p moment of the
      energy dissipation field in fully developed turbulence is studied in a range
      which extends to negative values of p. The curve tau(p) vs p and its derivative
      tau(')(p) are estimated in various ways, including a two-scale method.
      Predictions of recent cascade models agree with our findings, within the
      statistical errors, for moderately large, positive p. Evident discrepancies
      already appear, however, in the interval pin[0,1], and sometimes become dramatic
      for p<0. In the discussion of a class of cascade models, we present a scaling law
      which relates different moments to one another.

PMID- 11969660
TI  - Magnetic helicity tensor for an anisotropic turbulence.
AB  - The evolution of the magnetic helicity tensor for a nonzero mean magnetic field
      and for large magnetic Reynolds numbers in an anisotropic turbulence is studied.
      It is shown that the isotropic and anisotropic parts of the magnetic helicity
      tensor have different characteristic times of evolution. The time of variation of
      the isotropic part of the magnetic helicity tensor is much larger than the
      correlation time of the turbulent velocity field. The anisotropic part of the
      magnetic helicity tensor changes for the correlation time of the turbulent
      velocity field. The mean turbulent flux of the magnetic helicity is calculated as
      well. It is shown that even a small anisotropy of turbulence strongly modifies
      the flux of the magnetic helicity. It is demonstrated that the tensor of the
      magnetic part of the alpha effect for weakly inhomogeneous turbulence is
      determined only by the isotropic part of the magnetic helicity tensor.

PMID- 11969661
TI  - Onset of oscillatory binary fluid convection in finite containers.
AB  - The onset of oscillatory convection in binary fluid mixtures in a two-dimensional
      domain with realistic boundary conditions on all boundaries is determined as a
      function of the fluid parameters and the aspect ratio Gamma of the container. The
      first unstable mode has either odd or even parity under left-right reflection.
      Depending on Gamma and the separation ratio S, this mode has the form of a
      standing wave, or a "chevron," consisting of a pair of waves propagating outwards
      from the cell center (or, in some cases, inwards towards it). Codimension--two
      points at which odd and even parity modes are simultaneously marginally stable
      are determined, as are various Takens-Bogdanov points. For fixed S<S(TB), all
      mode interactions among modes of like parity, arising as Gamma varies, are of the
      nonresonant Hopf-Hopf type; however, the details of the modal interchange are
      organized by resonant Hopf bifurcations with 1:1 resonance. Particular attention
      is paid to the asymptotic mode structure as Gamma-->infinity, and to the gap (in
      Rayleigh number and oscillation frequency) between successively unstable modes.
      The results quantify the parameter regime in which the weakly nonlinear dynamics
      of the system can be described in terms of the interaction of the first odd and
      even parity oscillatory modes.

PMID- 11969662
TI  - Droplet formation by rapid expansion of a liquid.
AB  - Molecular dynamics of two- and three-dimensional liquids undergoing a homogeneous
      adiabatic expansion provides a direct numerical simulation of the atomization
      process. The Lennard-Jones potential is used with different force cutoff
      distances; the cluster distributions do not depend strongly on the cutoff
      parameter. Expansion rates, scaled by the natural molecular time unit (about a
      picosecond), are investigated from unity down to 0.01; over this range the mean
      droplet size follows the scaling behavior of an energy balance model which
      minimizes the sum of kinetic plus surface energy. A second model which equates
      the elastic stored energy to the surface energy gives better agreement with the
      simulation results. The simulation results indicate that both the mean and the
      maximum droplet size have a power-law dependence upon the expansion rate; the
      exponents are -2d/3 (mean) and -d/2 (maximum), where d is the dimensionality. The
      mean does not show a dependence upon the system size, whereas the maximum does
      increase with system size, and furthermore, its exponent increases with an
      increase in the force cutoff distance. A mean droplet size of 2.8/eta(2), where
      eta is the expansion rate, describes our high-density three-dimensional
      simulation results, and this relation is also close to experimental results from
      the free-jet expansion of liquid helium. Thus, one relation spans a cluster size
      range from one atom to over 40 million atoms. The structure and temperature of
      the atomic clusters are described.

PMID- 11969663
TI  - Correlation functions in isotropic and anisotropic turbulence: the role of the
      symmetry group.
AB  - The theory of fully developed turbulence is usually considered in an idealized
      homogeneous and isotropic state. Real turbulent flows exhibit the effects of
      anisotropic forcing. The analysis of correlation functions and structure
      functions in isotropic and anisotropic situations is facilitated and made
      rational when performed in terms of the irreducible representations of the
      relevant symmetry group which is the group of all rotations SO(3). In this paper
      we first consider the needed general theory, and explain why we expect different
      (universal) scaling exponents in the different sectors of the symmetry group. We
      exemplify the theory context of isotropic turbulence (for third order tensorial
      structure functions) and in weakly anisotropic turbulence (for the second order
      structure function). The utility of the resulting expressions for the analysis of
      experimental data is demonstrated in the context of high Reynolds number
      measurements of turbulence in the atmosphere.

PMID- 11969664
TI  - Effective Hamiltonian for liquid-vapor interfaces.
AB  - Starting from a density functional theory for inhomogeneous fluids we derive an
      effective Hamiltonian for liquid-vapor interfaces of simple fluids which goes
      beyond the common phenomenological capillary-wave description. In contrast to
      other approaches we take into account the long-ranged power-law decay of the
      dispersion forces between the fluid particles which changes the functional form
      of the wave-vector-dependent surface tension qualitatively. In particular, we
      find two different forms of the bending rigidity for the capillary waves, a
      negative one for small wave vectors determined by the long-ranged dispersion
      forces and a positive rigidity for large wave vectors due to the distortions of
      the intrinsic density profile in the vicinity of the locally curved interface.
      The differences to the standard capillary-wave theory and the relevance of these
      results for the interpretation of scattering experiments are discussed.

PMID- 11969665
TI  - Symmetries and induced effects in bilayer and multilayer antiferroelectric and
      ferrielectric liquid crystal phases.
AB  - The stable antiferroelectric and ferrielectric smectic phases which may arise
      below a chiral SmA* phase are investigated theoretically. The symmetry and
      physical properties of the bilayer and multilayer configurations are worked out.
      Antiferroelectric and ferrielectric bilayer and multilayer configurations,
      possessing an induced spontaneous ferroelectric polarization component
      perpendicular to the smectic layers, are shown to take place, as the result of a
      nonlinear piezoelectric effect. These states of low polar symmetries occur when
      the angle between the inlayer projections of the dipoles and the director of the
      molecules is different from 90 degrees.

PMID- 11969666
TI  - Photon transmission technique for studying multiple phase transitions in a liquid
      crystal.
AB  - A photon transmission technique was used to monitor the multiple phase
      transitions in a 4-butoxyphenyl4(')-declyoxybenzoate (BOPDOB) liquid crystal.
      Drastic decreases in the transmitted photon intensity (I) were attributed to the
      sequential phase transitions in BOPDOB upon cooling. In this paper, it is assumed
      that the order parameter rho is proportional to the transmitted photon intensity.
      The isotropic-nematic and nematic-smectic-A transitions were observed and found
      to be of first order. It was observed that the smectic-A-smectic-C and smectic-C
      smectic-G transitions are second order. It was found that for the smectic-A
      smectic-C transition, critical exponent crosses over from beta=0.513+/-0.006,
      which is consistent with mean-field theory, to beta=0.35+/-0.009, which is
      consistent with heliumlike behavior, as the Ginzburg criterion predicts. The
      critical exponent for the smectic-C-smectic-G transition was found to be
      beta=0.703+/-0.001. Transition temperatures were established at each phase
      transitions and found to be 84.92 degrees C, 74.85 degrees C, 52.96 degrees C,
      and 33.03 degrees C for isotropic-nematic, nematic-smectic-A, smectic-A-smectic-C
      and, smectic-C-smectic-G transitions, respectively.

PMID- 11969667
TI  - Rotational viscosity in a nematic liquid crystal: a theoretical treatment and
      molecular dynamics simulation.
AB  - The rotational viscosity coefficient gamma(1) of 4-n-pentyl-4(')-cyanobiphenyl in
      the nematic phase is investigated by combination of existing statistical
      mechanical approaches (SMAs), based on a rotational diffusion model and computer
      simulation technique. The SMAs rest on a model in which it is assumed that the
      reorientation of an individual molecule is a stochastic Brownian motion in a
      certain potential of mean torque. According to the SMAs, gamma(1) is found to be
      a function of temperature, density, rotational diffusion coefficient, and a
      number of order parameters (OPs). The diffusion coefficient and the OPs were
      obtained from an analysis of a trajectory generated in a molecular dynamics
      simulation using realistic atom-atom interactions. In addition, a set of
      experimentally determined diffusion coefficients and OPs was used for evaluation
      of gamma(1). Reasonable agreement between calculated and experimental values of
      gamma(1) is obtained. It is shown that near the clearing point gamma(1) is
      proportional to (-)P22, where (-)P2 is the second-rank OP. This limiting value of
      gamma(1) is in agreement with mean-field theory.

PMID- 11969668
TI  - Organization of cyanobiphenyl liquid crystal molecules in prewetting films
      spreading on silicon wafers.
AB  - We observe prewetting films of 8CB (4'-n-octyl-4-cyanobiphenyl) spreading at room
      temperature on silicon wafers by ellipsometry and x-ray reflectivity.
      Ellipsometry indicates the formation of a nondense monolayer spreading in front
      of a 45-A-thick film. X-ray reflectivity, performed using a ribbon geometry for
      the liquid crystal (LC) reservoir, allows us to determine the organization of the
      8CB molecules in the homogenous film. It consists of a trilayer stacking with a
      smecticlike bilayer standing above a polar monolayer with tilted molecules. We
      show that the thickness of the bilayer is equal to the smectic periodicity in the
      bulk material and that the tilt angle of the molecules in contact with the solid
      surface is close to 60 degrees, in good agreement with second-harmonic generation
      studies reported by other groups. Such organization can be precisely determined
      using x-ray reflectivity because it induces a modulation of the electron density
      along the normal to the surface. Furthermore, a study of the ellispometric
      profile of a drop heated in the nematic phase, where we observe a complete
      spreading of the LC, shows the complex structuration of the LC close to the solid
      interface. In particular, the spreading behavior of the trilayer compared to the
      subsequent smecticlike bilayers indicates the existence of specific interaction
      between the trilayer and silicon wafer.

PMID- 11969669
TI  - Trapping and mobilization of residual fluid during capillary desaturation in
      porous media.
AB  - We discuss the problem of trapping and mobilization of nonwetting fluids during
      immiscible two-phase displacement processes in porous media. Capillary
      desaturation curves give residual saturations as a function of capillary number.
      Interpreting capillary numbers as the ratio of viscous to capillary forces the
      breakpoint in experimental curves contradicts the theoretically predicted force
      balance. We show that replotting the data against a novel macroscopic capillary
      number resolves the problem for discontinuous mode displacement.

PMID- 11969670
TI  - Freezing and glass transition of hard spheres in cavities.
AB  - Dynamical and static properties of N=13-4000 hard spheres in spherical cavities
      with smooth and rough walls have been calculated by molecular-dynamics computer
      simulations. We use a dynamical criterion to distinguish between fluidlike and
      solidlike states. The associated crossover densities show a strong dependence
      both on the system size and on the surface roughness. For large N, these
      crossover densities tend to the bulk glass transition density for rough walls and
      to the bulk crystallization density for smooth walls. The crossover densities for
      finite N are found to be significantly smaller than the corresponding bulk
      densities. A detailed examination of the layer-resolved radial- and tangential
      mean-square displacements reveals qualitatively different dynamics for smooth and
      rough cavities.

PMID- 11969671
TI  - Density fluctuations in a model for vibrated granular media.
AB  - This paper presents the study of density fluctuations in a model for vibrated
      granular media. Their microscopic origin is shown to be linked to the microscopic
      disorder in grains packing. Varying vibrations amplitude and duration, several
      regimes are found for density relaxation. Its power spectrum is well described by
      power laws.

PMID- 11969672
TI  - Low-temperature interface between the gas and solid phases of hard spheres with a
      short-ranged attraction.
AB  - At low temperature, spheres with a very short-ranged attraction exist as a near
      close-packed solid coexisting with an almost infinitely dilute gas. We find that
      the ratio of the interfacial tension between these two phases to the thermal
      energy diverges as the range of the attraction tends to zero. The large tensions
      when the interparticle attractions are short ranged may be why globular proteins
      only crystallize over a narrow range of conditions.

PMID- 11969673
TI  - Viscoelastic model of phase separation in colloidal suspensions and emulsions.
AB  - We propose a simple physical model of phase separation of colloidal suspensions
      and emulsions, which we call the "viscoelastic model." On the basis of this
      model, we consider two poorly understood phenomena: (i) phase separation
      accompanying the formation of a transient gel, and its collapse, and (ii) shear
      effects on composition fluctuations and phase separation. These phenomena can be
      explained by "asymmetric stress division" between the components of a mixture due
      to their size difference; the interaction network of particles can store elastic
      energy, while a fluid component cannot. The importance of the bulk stress
      stemming from an interaction network is discussed, using a concept of self
      induced elastic constraint due to connectivity. We argue that there are common
      features to polymer solutions, colloidal suspensions, emulsions, and possibly
      protein solutions. They originate from dynamic asymmetry between the components
      and the resulting interaction network of the slower component of a mixture, which
      leads to the formation of a transient gel.

PMID- 11969674
TI  - Polymer depletion effects near mesoscopic particles.
AB  - The behavior of mesoscopic particles dissolved in a dilute solution of long,
      flexible, and nonadsorbing polymer chains is studied by field-theoretic methods.
      For spherical and cylindrical particles the solvation free energy for immersing a
      single particle in the solution is calculated explicitly. Important features are
      qualitatively different for self-avoiding polymer chains as compared with ideal
      chains. The results corroborate the validity of the Helfrich-type curvature
      expansion for general particle shapes and allow for quantitative experimental
      tests. For the effective interactions between a small sphere and a wall, between
      a thin rod and a wall, and between two small spheres, quantitative results are
      presented. A systematic approach for studying effective many-body interactions is
      provided. The common Asakura-Oosawa approximation modeling the polymer coils as
      hard spheres turns out to fail completely for small particles and still fails by
      about 10% for large particles.

PMID- 11969675
TI  - Kinetic model for a step edge in epitaxial growth.
AB  - A kinetic theory is formulated for the velocity of a step edge in epitaxial
      growth. The formulation involves kinetic, mean-field equations for the density of
      kinks and "edge adatoms" along the step edge. Equilibrium and kinetic steady
      states, corresponding to zero and nonzero deposition flux, respectively, are
      derived for a periodic sequence of step edges. The theoretical results are
      compared to results from kinetic Monte Carlo (KMC) simulations of a simple solid
      on-solid model, and excellent agreement is obtained. This theory provides a
      starting point for modeling the growth of two-dimensional islands in molecular
      beam epitaxy through motion of their boundaries, as an alternative to KMC
      simulations.

PMID- 11969676
TI  - Dielectric investigation of the temperature dependence of the nonexponentiality
      of the dynamics of polymer melts.
AB  - Using broad band dielectric spectroscopy (10(-5)-10(9) Hz), combining time domain
      and frequency domain techniques, we study the temperature dependence of the non
      Debye character of the alpha relaxation of polymer melts in the glass transition
      temperature T(g) range. The alpha relaxation process is described in terms of the
      Kohlrausch-Williams-Watts relaxation function which has a single parameter beta
      to characterize the nonexponentiality of the relaxation. At high temperatures,
      beta remains nearly insensitive to temperature changes, whereas in the vicinity
      of T(g) a nearly linear increasing of beta with temperature is found. The
      temperature range where the change of the beta(T) behavior occurs is located for
      all the polymers investigated around 1.2T(g). Moreover, our results indicate a
      common value of beta approximately equal to 1/3 at the temperature where the
      relaxation time diverges. The beta(T) behavior near T(g) is discussed in terms of
      a "rugged landscape" phase space which allows us to rationalize both the beta(T)
      behavior observed as well as the similarities of our findings near T(g) with the
      results reported in simulations on Ising spin glasses and other model systems.

PMID- 11969677
TI  - Evolution of avalanche conducting states in electrorheological liquids.
AB  - Charge transport in electrorheological fluids is studied experimentally under
      strongly nonequilibrium conditions. By injecting an electrical current into a
      suspension of conducting nanoparticles we are able to initiate a process of self
      organization which leads, in certain cases, to formation of a stable pattern
      which consists of continuous conducting chains of particles. The evolution of the
      dissipative state in such a system is a complex process. It starts as an
      avalanche process characterized by nucleation, growth, and thermal destruction of
      such dissipative elements as continuous conducting chains of particles as well as
      electroconvective vortices. A power-law distribution of avalanche sizes and
      durations, observed at this stage of the evolution, indicates that the system is
      in a self-organized critical state. A sharp transition into an avalanche-free
      state with a stable pattern of conducting chains is observed when the power
      dissipated in the fluid reaches its maximum. We propose a simple evolution model
      which obeys the maximum power condition and also shows a power-law distribution
      of the avalanche sizes.

PMID- 11969678
TI  - Crystallization by settling in suspensions of hard spheres.
AB  - We examine crystallization by settling for two different model hard-sphere
      suspensions. Sedimentation velocities, internal shock velocities, and crystal
      growth velocities are measured. Dynamic light scattering experiments measure
      volume fraction profiles in fluid phases, while Bragg scattering experiments
      determine volume fraction profiles in crystal phases. Centrifugation experiments
      determine the particle Peclet number above which samples will not crystallize.
      The sedimentation velocities, as a function of volume fraction, agree with other
      "hard-sphere" data. Remarkably, the value of the reduced crystal growth velocity
      (approximately 0.075) obtains for two orders of magnitude of the particle Peclet
      number. Kynch theory provides an adequate description of the data in the fluid
      phase, but is less adequate for volume fraction profiles in the crystal phase.
      The crystals in the dense sediment are compressed more along a vertical axis
      relative to the horizontal axis. Predicted Wilson-Frenkel crystal growth
      velocities, calculated using known hard-sphere equations of state and a short
      time self-diffusion constant, rationalize the measured crystal growth velocities.

PMID- 11969679
TI  - Multifractality of Brownian motion near absorbing polymers.
AB  - We characterize the multifractal behavior of Brownian motion in the vicinity of
      an absorbing star polymer. We map the problem to an O(M)-symmetric phi(4)-field
      theory relating higher moments of the Laplacian field of Brownian motion to
      corresponding composite operators. The resulting spectra of scaling dimensions of
      these operators display the convexity properties that are necessarily found for
      multifractal scaling but unusual for power of field operators in field theory.
      Using a field-theoretic renormalization group approach we obtain the multifractal
      spectrum for absorption at the core of a polymer star as an asymptotic series. We
      evaluate these series using resummation techniques.

PMID- 11969680
TI  - Broadband dielectric spectroscopy on glass-forming propylene carbonate.
AB  - Dielectric spectroscopy covering more than 18 decades of frequency has been
      performed on propylene carbonate in its liquid and supercooled-liquid state.
      Using quasioptic submillimeter and far-infrared spectroscopy, the dielectric
      response was investigated up to frequencies well into the microscopic regime. We
      discuss the alpha process whose characteristic time scale is observed over 14
      decades of frequency and the excess wing showing up at frequencies some three
      decades above the peak frequency. Special attention is given to the high
      frequency response of the dielectric loss in the crossover regime between alpha
      peak and boson peak. Similar to our previous results in other glass-forming
      materials, we find evidence for additional processes in the crossover regime.
      However, significant differences concerning the spectral form at high frequencies
      are found. We compare our results to the susceptibilities obtained from light
      scattering and to the predictions of various models of the glass transition.

PMID- 11969681
TI  - Thermodynamic perturbation theory for polydisperse colloidal suspensions using
      orthogonal polynomial expansions.
AB  - We present a method for calculating the thermodynamic and structural properties
      of a polydisperse liquid by means of a thermodynamic perturbation theory: the
      optimized random phase approximation (ORPA). The approach is an extension of a
      method proposed recently by one of us for an integral equation application [Phys.
      Rev. E 54, 4411 (1996)]. The method is based on expansions of all sigma-dependent
      functions in the orthogonal polynomials p(i)(sigma) associated with the weight
      function f(Sigma)(sigma), where sigma is a random variable (in our case the size
      of the particles) with distribution f(Sigma)(sigma). As in the one-component or
      general N-component case, one can show that the solution of the ORPA is
      equivalent to the minimization of a suitably chosen functional with respect to
      variations of the direct correlation functions. To illustrate the method, we
      study a polydisperse system of square-well particles; extension to other hard
      core or soft-core systems is straightforward.

PMID- 11969682
TI  - Impurity mediated nucleation in hexadecane-in-water emulsions.
AB  - We report detailed nucleation studies on the liquid-to-solid transition of
      hexadecane using nearly monodisperse hexadecane-in-water emulsions. A careful
      consideration of the kinetics of isothermal and nonisothermal freezing shows
      deviations from predictions of classical nucleation theory, if one assumes that
      the emulsion droplet population is homogeneous. Similar deviations have been
      observed previously (3). As an explanation, we propose an argument based on the
      dynamic generation of droplet heterogeneity mediated by mobile impurities. This
      proposal is in good agreement with existing data.

PMID- 11969683
TI  - Bethe lattice representation for sandpiles.
AB  - Avalanches in sandpiles are represented by a process of percolation in a Bethe
      lattice with a feedback mechanism. The results indicate that the frequency
      spectrum and probability distribution of avalanches provide a better resemblance
      to the experimental results than other models using cellular automata
      simulations. Apparent discrepancies between experiments performed by different
      authors are reconciled. Critical behavior is expressed here by the critical
      properties of percolation phenomena.

PMID- 11969684
TI  - Characteristics of slow and fast ion dynamics in a lithium metasilicate glass.
AB  - Molecular dynamics simulations of lithium metasilicate (Li(2)SiO(3)) glass have
      been performed. The motion of lithium ions is divided into slow (A) and fast (B)
      categories in the glassy state. The waiting time distribution of the jump motion
      of each component shows power law behavior with different exponents. Slow
      dynamics are caused by localized jump motions and the long waiting time. On the
      other hand, the fast dynamics of the lithium ions in Li(2)SiO(3) are
      characterized as Levy flight caused by cooperative jumps. Short intervals of jump
      events also occur in the fast dynamics in the short time region. Both the
      temporal and spatial terms contribute to the dynamics acceleration and the
      heterogeneity caused by these two kinds of dynamics is illustrated. The slow
      dynamics characteristics of the "glass transition" and in the "mixed alkali
      effect" are discussed.

PMID- 11969685
TI  - Hydrodynamics of resonance oscillations of columns of inelastic particles.
AB  - We study oscillations of a one-dimensional (1D) column of N slightly inelastic
      particles, produced by a piston vibrating at one end of a closed tube. It is
      found that for large enough vibrational amplitudes of the piston, the column
      oscillates periodically with the period equal to the vibrational period. The
      oscillation patterns are governed by the shock waves propagating across the
      column. The averaged kinetic energy per particle is shown to be proportional to
      the square of the vibrational frequency, omega. This energy also strongly depends
      on the vibrational amplitude. The maximal value of this kinetic energy achievable
      by these external vibrations is found to be of order omega(2)L(2), where L is the
      total volume (length) of the tube free of particles. The above results on the
      column resonance oscillations are also predicted by a 3D hydrodynamic model of an
      inelastic granular gas.

PMID- 11969686
TI  - Theory of ocular dominance pattern formation.
AB  - We investigate a general and analytically tractable model for the activity
      dependent formation of neuronal connectivity patterns. Previous models are
      contained as limiting cases. As an important example we analyze the formation of
      ocular dominance patterns in the visual cortex. A linear stability analysis
      reveals that the model undergoes a Turing-type instability as a function of
      interaction range and receptive field size. The phase transitions is of second
      order. After the linear instability the patterns may reorganize which we analyze
      in terms of a potential for the dynamics. Our analysis demonstrates that the
      experimentally observed dependency of ocular dominance patterns on interocular
      correlations of visual experience during development can emerge according to two
      generic scenarios: either the system is driven through the phase transition
      during development thereby selecting and stabilizing the first unstable mode or a
      primary pattern reorganizes towards larger wavelength according their lower
      energy. Experimentally observing the time course of ocular dominance pattern
      formation will decide which scenario is realized in the brain.

PMID- 11969687
TI  - Simple central pattern generator model using phasic analog neurons.
AB  - Many biological neurons (called phasic or adapting neurons) display neural
      adaptation: their response to a constant input diminishes with time. A simple
      method of adding adaptive firing thresholds to existing analog (or graded
      response) neural models is described. A half-center central pattern generator is
      modeled using two mutually inhibitory phasic analog neurons. Hopf bifurcation
      analysis shows that oscillatory solutions will arise if the mutual inhibition is
      sufficiently strong, and allows us to characterize the stability of the cycles
      which arise.

PMID- 11969688
TI  - Genetic correlations in mutation processes.
AB  - We study the role of phylogenetic trees on correlations in mutation processes.
      Generally, correlations decay exponentially with the generation number. We find
      that two distinct regimes of behavior exist. For mutation rates smaller than a
      critical rate, the underlying tree morphology is almost irrelevant, while
      mutation rates higher than this critical rate lead to strong tree-dependent
      correlations. We show analytically that identical critical behavior underlies all
      multiple point correlations. This behavior generally characterizes branching
      processes undergoing mutation.

PMID- 11969689
TI  - Markov analysis of stochastic resonance in a periodically driven integrate-and
      fire neuron.
AB  - We model the dynamics of the leaky integrate-and-fire neuron under periodic
      stimulation as a Markov process with respect to the stimulus phase. This avoids
      the unrealistic assumption of a stimulus reset after each spike made in earlier
      papers and thus solves the long-standing reset problem. The neuron exhibits
      stochastic resonance, both with respect to input noise intensity and stimulus
      frequency. The latter resonance arises by matching the stimulus frequency to the
      refractory time of the neuron. The Markov approach can be generalized to other
      periodically driven stochastic processes containing a reset mechanism.

PMID- 11969690
TI  - Absence of a vestigial vapor pressure paradox.
AB  - The enigmatic but much accepted vapor pressure paradox for oriented lipid bilayer
      samples was recently justified theoretically. Subsequently, recent experiments
      have shown that there is no vapor pressure paradox. The first result of this
      paper is to consider another degree of freedom that reverses the previous
      theoretical conclusion, so that theory and experiment are now in agreement that
      there is no vapor pressure paradox. However, this analysis also suggests the
      possibility of a vestigial vapor pressure paradox that would rationalize why the
      vapor pressure paradox was historically so persistent and that would have led to
      an improved protocol for obtaining bilayer structure. This vestigial vapor
      pressure paradox would involve a phase transition as a function of applied
      osmotic pressure. We test this possibility experimentally using combined neutron
      and x-ray scattering data. The conclusion from these experiments is that there is
      not even a vestigial vapor pressure paradox. However, this negative result
      validates an improved method for calibrating osmotic pressure in x-ray studies of
      oriented samples.

PMID- 11969691
TI  - Lubricating bacteria model for branching growth of bacterial colonies.
AB  - Various bacterial strains (e.g., strains belonging to the genera Bacillus,
      Paenibacillus, Serratia, and Salmonella) exhibit colonial branching patterns
      during growth on poor semisolid substrates. These patterns reflect the bacterial
      cooperative self-organization. A central part of the cooperation is the
      collective formation of a lubricant on top of the agar which enables the bacteria
      to swim. Hence it provides the colony means to advance towards the food. One
      method of modeling the colonial development is via coupled reaction-diffusion
      equations which describe the time evolution of the bacterial density and the
      concentrations of the relevant chemical fields. This idea has been pursued by a
      number of groups. Here we present an additional model which specifically includes
      an evolution equation for the lubricant excreted by the bacteria. We show that
      when the diffusion of the fluid is governed by a nonlinear diffusion coefficient,
      branching patterns evolve. We study the effect of the rates of emission and
      decomposition of the lubricant fluid on the observed patterns. The results are
      compared with experimental observations. We also include fields of chemotactic
      agents and food chemotaxis and conclude that these features are needed in order
      to explain the observations.

PMID- 11969692
TI  - Modeling of spatiotemporal patterns in bacterial colonies.
AB  - A diffusion-reaction model for the growth of bacterial colonies is presented. The
      often observed cooperative behavior developed by bacteria which increases their
      motility in adverse growth conditions is here introduced as a nonlinear diffusion
      term. The presence of this mechanism depends on a response which can present
      hysteresis. By changing only the concentrations of agar and initial nutrient,
      numerical integration of the proposed model reproduces the different patterns
      shown by Bacillus subtilis OG-01.

PMID- 11969693
TI  - Self-focusing, channel formation, and high-energy ion generation in interaction
      of an intense short laser pulse with a He jet.
AB  - Using interferometry, we investigate the dynamics of interaction of a
      relativistically intense 4-TW, 400-fs laser pulse with a He gas jet. We observe a
      stable plasma channel 1 mm long and less than 30 microm in diameter, with a
      radial gradient of electron density approximately 5 x 10(22) cm(-4) and with an
      on-axis electron density approximately ten times less than its maximum value of 8
      x 10(19) cm(-3). A high radial velocity of the surrounding gas ionization of
      approximately 3.8 x 10(8) cm/s has been observed after the channel formation, and
      it is attributed to the fast ions expelled from the laser channel and propagating
      radially outward. We developed a kinetic model which describes the plasma channel
      formation and the subsequent ambient gas excitation and ionization. Comparing the
      model predictions with the interferometric data, we reconstructed the axial
      profile of laser channel and on-axis laser intensity. The estimated maximum
      energy of accelerated ions is about 500 keV, and the total energy of the fast
      ions is 5% of the laser pulse energy.

PMID- 11969694
TI  - Theory of dust voids in plasmas.
AB  - Dusty plasmas in a gas discharge often feature a stable void, i.e., a dust-free
      region inside the dust cloud. This occurs under conditions relevant to both
      plasma processing discharges and plasma crystal experiments. The void results
      from a balance of the electrostatic and ion drag forces on a dust particle. The
      ion drag force is driven by a flow of ions outward from an ionization source and
      toward the surrounding dust cloud, which has a negative space charge. In
      equilibrium the force balance for dust particles requires that the boundary with
      the dust cloud be sharp, provided that the particles are cold and monodispersive.
      Numerical solutions of the one-dimensional nonlinear fluid equations are carried
      out including dust charging and dust-neutral collisions, but not ion-neutral
      collisions. The regions of parameter space that allow stable void equilibria are
      identified. There is a minimum ionization rate that can sustain a void. Spatial
      profiles of plasma parameters in the void are reported. In the absence of ion
      neutral collisions, the ion flow enters the dust cloud's edge at Mach number M=1.
      Phase diagrams for expanding or contracting voids reveal a stationary point
      corresponding to a single stable equilibrium void size, provided the ionization
      rate is constant. Large voids contract and small voids expand until they attain
      this stationary void size. On the other hand, if the ionization rate is not
      constant, the void size can oscillate. Results are compared to recent laboratory
      and microgravity experiments.

PMID- 11969695
TI  - Time correlation of momentum in a collisionless plasma due to large fluctuations.
AB  - The present paper shows that in one-dimensional collisionless plasma, due to
      large fluctuation, the time correlation of momentum asymptotically behaves
      inverse quadratically with time. The long-time tail correlation is closely
      related to nonlinear Landau damping [M.B. Isichenko, Phys. Rev. Lett. 78, 2369
      (1997)]. Furthermore, it reveals the possible relationship between fluctuation
      and dispersion. The result indicates that the long-time tail correlation can also
      occur in a reversibly dispersive system, where the previous theories are invalid.
      A by-product proves that it may be efficient to investigate the dispersive
      features of collisionless plasma in view of time correlation.

PMID- 11969696
TI  - Discharge impedance of solenoidal inductively coupled plasma discharge.
AB  - The discharge impedance is calculated for a solenoidal inductively coupled plasma
      (ICP) discharge, which is one of the important sources for plasma processing. To
      calculate this impedance, the electromagnetic field quantities are obtained by
      solving the two-dimensional Maxwell equations in a realistic geometry. Also
      considered in the calculation is the anomalous skin effect which is regarded as a
      collisionless heating mechanism of ICP discharge. The results show that the
      discharge impedance is a function of various discharge parameters, such as plasma
      density, electron temperature, antenna position, collision frequency, excitation
      frequency, and chamber geometry.

PMID- 11969697
TI  - Subpicosecond pulse laser absorption by an overdense plasma with variable
      ionization.
AB  - Transient ionization of an overdense plasma produced by a subpicosecond, p
      polarized obliquely incident pulse laser of moderate intensity (10(16)-10(18)
      W/cm(2)) changes the plasma heat transfer via processes dominated by the return
      current and the absorption rate via ion acceleration. To explore the effect of
      variable ionization, a hybrid one-dimensional electro-magnetic particle-in-cell
      method that conforms to a direct solution of the Fokker-Planck-Landau equation is
      applied. A method that includes the Langevin equation to account for Coulomb
      collisions and the average ion model to calculate the nonlocal thermodynamic
      equilibrium ionization balance provides good agreement between the computed
      absorption and the measured results.

PMID- 11969698
TI  - Superconfiguration accounting approach versus average-atom model in local
      thermodynamic-equilibrium highly ionized plasmas.
AB  - Statistical methods of describing and simulating complex ionized plasmas requires
      the development of reliable and computationally tractable models. In that spirit,
      we propose the screened-hydrogenic average atom, augmented with corrections
      resulting from fluctuations of the occupation probabilities around the mean-field
      equilibrium, as an approximation to calculate the grand potential and related
      statistical properties. Our main objective is to check the validity of this
      approach by comparing its predictions with those given by the superconfiguration
      accounting method. The latter is well-suited to this purpose. In effect, this
      method makes it possible to go beyond the mean-field model by using
      nonperturbative, analytic, and systematic techniques. Besides, it allows us to
      establish the relationship between the detailed configuration accounting and the
      average-atom methods. To our knowledge, this is the first time that the
      superconfiguration description has been used in this context. Finally, this study
      is also the occasion for presenting a powerful technique from analytic number
      theory to calculate superconfiguration averaged quantities.

PMID- 11969699
TI  - Formation of plasma channels in the interaction of a nanosecond laser pulse at
      moderate intensities with helium gas jets.
AB  - We report on a detailed study of channel formation in the interaction of a
      nanosecond laser pulse with a He gas jet. A complete set of diagnostics is used
      in order to characterize the plasma precisely. The evolution of the plasma radius
      and of the electron density and temperature are measured by Thomson scattering,
      Schlieren imaging, and Mach-Zehnder interferometry. In gas jets, one observes the
      formation of a channel with a deep density depletion on axis. Because of
      ionization-induced defocusing which increases the size of the focal spot and
      decreases the maximum laser intensity, no channel is observed in the case of a
      gas-filled chamber. The results obtained in various gas-jet and laser conditions
      show that the channel radius, as well as the density along the propagation axis,
      can be adjusted by changing the laser energy and gas-jet pressure. This is a
      crucial issue when one wants to adapt the channel parameters in order to guide a
      subsequent high-intensity laser pulse. The experimental results and their
      comparison with one-dimensional (1D) and two-dimensional hydrodynamic simulations
      show that the main mechanism for channel formation is the hydrodynamic evolution
      behind a supersonic electron heat wave propagating radially in the plasma. It is
      also shown from 2D simulations that a fraction of the long pulse can be self
      guided in the channel it creates. The preliminary results and analyses on this
      subject have been published before [V. Malka et al., Phys. Rev. Lett. 79, 2979
      (1997)].

PMID- 11969700
TI  - Confinement physics for thermal, neutral, high-charge-state plasmas in nested
      well solenoidal traps.
AB  - A theoretical study is presented which indicates that it is possible to confine a
      neutral plasma using static electric and solenoidal magnetic fields. The plasma
      consists of equal temperature electrons and highly stripped ions. The solenoidal
      magnetic field provides radial confinement, while the electric field, which
      produces an axial nested-well potential profile, provides axial confinement. A
      self-consistent, multidimensional numerical solution for the electric potential
      is obtained, and a fully kinetic theoretical treatment on axial transport is used
      to determine an axial confinement time scale. The effect on confinement of the
      presence of a radial electric field is explored with the use of ion trajectory
      calculations. A thermal, neutral, high-charge-state plasma confined in a nested
      well trap opens new possibilities for fundamental studies on plasma recombination
      and cross-field transport processes under highly controlled conditions.

PMID- 11969701
TI  - Spatial coherence of bending magnet radiation and application limit of the van
      Cittert-Zernike theorem.
AB  - In this paper we discuss how the first-order spatial coherence of bending magnet
      radiation is determined. We present an analytical representation of the coherence
      and compare it with the numerical calculations based on the first principles. It
      is shown that if the electron-beam size is so large that some conditions are
      satisfied, the van Cittert-Zernike theorem can be used without any modification
      in the vertical and horizontal directions. The formalism presented will be useful
      in judging whether or not the electron-beam size in the storage ring can be
      estimated directly from the van Cittert-Zernike theorem using the synchrotron
      radiation interferometer.

PMID- 11969702
TI  - Conservation law for multimoded nonlinear optical waveguide interactions and its
      physical interpretation.
AB  - The swapping of power between the modes of cw waves in lossless nonlinear optical
      waveguides always admit two conserved quantities, the total power and one other,
      which is sometimes identified as a Hamiltonian. We show that a general
      formulation of this Hamiltonian is in fact the weak guidance limit for cw waves
      of a more general conservation law. We make the link between this more general
      conservation law and the conservation of "wave" momentum, where wave momentum is
      a combination of both real momentum and so-called pseudomomentum. This allows us
      to interpret the conserved Hamiltonian in physical terms.

PMID- 11969703
TI  - Optical gap solitons in nonresonant quadratic media.
AB  - We demonstrate an important role of the process of optical rectification in the
      theory of nonlinear wave propagation in quadratically nonlinear [or chi(2)]
      periodic optical media. We derive a novel physical model for gap solitons in
      chi(2) nonlinear Bragg gratings.

PMID- 11969704
TI  - Geometrical and wave optics of paraxial beams.
AB  - Most calculational techniques used to evaluate beam propagation are geared
      towards either fully coherent or fully incoherent beams. The intermediate partial
      coherence regime, while in principle known for a long time, has received
      comparably little attention so far. The resulting shortage of adequate
      calculational techniques is currently being felt in the realm of x-ray optics
      where, with the advent of third generation synchrotron light sources, partially
      coherent beams become increasingly common. The purpose of this paper is to
      present a calculational approach which, utilizing a "variance matrix"
      representation of paraxial beams, allows for a straightforward evaluation of wave
      propagation through an optical system. Being capable of dealing with an arbitrary
      degree of coherence, this approach covers the whole range from wave to ray
      optics, in a seamless fashion.

PMID- 11969705
TI  - Delay-time statistics for diffuse waves.
AB  - We formulate a theory for the statistics of the dynamics of a classical wave
      propagating in random media by analyzing the frequency derivative of the phase
      under the assumption of a Gaussian process. We calculate frequency correlations
      and probability distribution functions of dynamical quantities, as well the first
      non-Gaussian C2 correction. In A. Z. Genack, P. Sebbah, M. Stoytchev, and B. A.
      van Tiggelen, Phys. Rev. Lett. 82, 715 (1999), microwave measurements have been
      performed to which this theory applies.

PMID- 11969706
TI  - Exact solitary-wave solutions of chi(2) Ginzburg-Landau equations.
AB  - A family of exact temporal solitary-wave solutions (dissipative solitons) to the
      equations governing second-harmonic generation in quadratically nonlinear optical
      waveguides, in the presence of linear bandwidth-limited gain at the fundamental
      harmonic and linear loss at the second harmonic, is found, and the existence
      domain for the solutions is delineated. Direct numerical simulations of the
      solitons demonstrate that, as well as the classical pulse solutions to the cubic
      Ginzburg-Landau equation, the dissipative solitons can propagate robustly over a
      considerable distance before the model's intrinsic instability leads to onset of
      "turbulence." Two-soliton bound states are also predicted and then found in the
      direct simulations. We estimate real values of the physical parameters necessary
      for the existence of the solitons predicted, and conclude that they can be
      observed experimentally. A promising application for the solitons is their use in
      closed-loop cavities.

PMID- 11969707
TI  - Time-dependent equation for the intensity in the diffusion limit using a higher
      order angular expansion.
AB  - The first two terms in the spherical-harmonic expansion (the P(1) approximation)
      of the radiative transfer equation yield the diffusion equation. This
      approximation applies to multiple scattering and results in a solution for the
      energy density, the gradient of which is proportional to the light intensity. In
      this work a higher-order spherical-harmonic expansion of the radiative transfer
      equation is developed. This equation applies to the radiant intensity rather than
      the energy density. The equation can be decomposed into two terms: a propagator
      term obtained from the determinant of the coupled equations describing the
      individual components of the intensity, and a mixing matrix that describes the
      cross coupling between different orders of the expansion. Using the Fourier
      transform, an approximation based on expanding at small wave vectors k leads to
      an equation similar to the diffusion equation. The equation is expected to
      predict the intensity for multiple scattering at earlier times and shorter
      distances than the diffusion equation can. The notion of an equivalent wave field
      is introduced.

PMID- 11969708
TI  - Structural and flow properties of binary media generated by fractional Brownian
      motion models.
AB  - In the present paper, the structural and flow properties of binary media
      generated by two-dimensional lattices that follow fractional Brownian motion
      statistics are studied. A modification of the midpoint displacement and random
      addition method is employed in order to generate multicell binary media with
      sizes that are considerably larger than the correlation length of the medium.
      Several structural properties, such as the autocorrelation function, the surface
      area, and the percolation threshold, are studied for different values of porosity
      and degree of correlation. In addition, transport properties are investigated in
      the above media, by solving numerically the momentum and continuity equations, to
      determine the absolute permeability of the medium in directions parallel and
      normal to the fractional Brownian motion (fBm) plane. It is found that multicell
      fBm porous media possess very interesting structural properties that are
      functions of the Hurst exponent and porosity, and are independent of the lattice
      size, in contrast to the traditional single-cell fBm media. In addition, they
      exhibit stronger structural correlation, lower specific surface area, higher
      percolation threshold, and lower permeabilities than those of the corresponding
      single-cell porous media.

PMID- 11969709
TI  - Lagrange meshes from nonclassical orthogonal polynomials.
AB  - The Lagrange-mesh numerical method has the simplicity of a mesh calculation and
      the accuracy of a variational calculation. A flexible general procedure for
      deriving an infinity of new Lagrange meshes related to orthogonal or
      nonorthogonal bases is introduced by using nonclassical orthogonal polynomials.
      As an application, different Lagrange meshes based on shifted Gaussian functions
      are constructed. A simple quantum-mechanical example shows that the Lagrange-mesh
      method may become more accurate than the original variational calculation with a
      nonorthogonal basis.

PMID- 11969710
TI  - Framework for testing random numbers in parallel calculations.
AB  - We propose a framework for testing the quality of random numbers in parallel
      calculations. The key idea is to study cross-correlations between distinct
      sequences of random numbers via correlations between various diffusing random
      walkers, each of which is governed by a distinct random number sequence. The
      asymptotic power-law behavior of the corresponding correlation functions yields
      exponents, which can be compared with exact theoretical results. Correlations
      prior to the asymptotic regime can be further investigated by other complementary
      methods. We demonstrate this approach by three efficient tests, which find
      correlations in various commonly used pseudorandom number generators. Finally, we
      discuss some ideas for applying this framework in other contexts.

PMID- 11969711
TI  - Voronoi-Delaunay analysis of voids in systems of nonspherical particles.
AB  - The Voronoi network is known to be a useful tool for the structural description
      of voids in the packings of spheres produced by computer simulations. In this
      article we extend the Voronoi-Delaunay analysis to packings of nonspherical
      convex objects. Main properties of the Voronoi network, which are known for
      systems of spheres, are valid for systems of any convex objects. A general
      numerical algorithm for calculation of the Voronoi network in three dimensions is
      proposed. It is based on the calculation of the trajectory of the imaginary empty
      sphere of variable size, moving inside a system (the Delaunay empty sphere
      method). Analysis of voids is presented for an ensemble of random straight lines
      and for a molecular dynamics model of liquid crystal. The spatial distribution of
      voids and a simple percolation analysis are obtained. The distributions of the
      bottleneck radii and the radii of spheres inscribed in the voids are calculated.

PMID- 11969712
TI  - Simple equation for earthquake distribution.
AB  - The earthquake distribution, the Gutenberg-Richter law, is obtained postulating a
      connection through a diffusion process between the kinetic energy of the active
      zone and the radiated energy. A link between the value of the critical exponent
      and the stress release is proposed.

PMID- 11969713
TI  - Some properties of multifractality at solid-on-solid growth processes.
AB  - It is shown that multifractality of large deposition probabilities observed in a
      simple model of crystal growth (the Das Sarma model with neglected surface
      diffusion, desorption, and hop) corresponds to another type of statistical
      distribution: multifractal Bernoulli distribution. Lognormal distribution is also
      discussed in this context.

PMID- 11969714
TI  - Unified algebraic Bethe ansatz for two-dimensional lattice models.
AB  - We develop a unified formulation of the quantum inverse scattering method for
      lattice vertex models associated to the nonexceptional A(2)(2r), A(2)(2r-1),
      B(1)(r), C(1)(r), D(1)(r+1), and D(2)(r+1) Lie algebras. We recast the Yang
      Baxter algebra in terms of different commutation relations between creation,
      annihilation, and diagonal fields. The solution of the D(2)(r+1) model is based
      on an interesting 16-vertex model, which is solvable without recourse to a Bethe
      ansatz.

PMID- 11969715
TI  - Effect of symmetry on volume conserving surface models.
AB  - We study the effect of symmetry on volume conserving models without deposition
      and evaporation. By using the master equation approach, we identify two types of
      stochastic continuum equation with a conservative noise, depending on the
      symmetry of hopping rate in diffusion rules. In the model with symmetric hopping
      rate, a Laplacian term is essentially absent from the continuum equation. The
      dynamic scaling of this model is thus determined by the nonlinear fourth order
      equation with a conservative noise. When the symmetry is broken, a Laplacian term
      may be present, so the asymptotic scaling behavior is governed by the Laplacian
      term with nonzero coefficient. We verify this result by investigating a simple
      discrete model analytically.

PMID- 11969716
TI  - Test of semiclassical amplitudes for quantum ray-splitting systems.
AB  - We compute semiclassically and numerically the weights of ray-splitting orbits in
      the density of states of a rectangular and an annular ray-splitting billiard. The
      agreement between the semiclassical and the numerical results is very good,
      confirming the necessity of including reflection and transmission coefficients of
      non-Newtonian ray-splitting orbits in semiclassical expressions for the density
      of states of ray-splitting systems.

PMID- 11969717
TI  - Anomalous transport and quantum-classical correspondence.
AB  - We present evidence that anomalous transport in the classical standard map
      results in strong enhancement of fluctuations in the localization length of
      quasienergy states in the corresponding quantum dynamics. This generic effect
      occurs even far from the semiclassical limit and reflects the interplay of local
      and global quantum suppression mechanisms of classically chaotic dynamics.
      Possible experimental scenarios are also discussed.

PMID- 11969718
TI  - Peak position of dissipation spectrum in turbulent boundary layers.
AB  - The peak locations of energy dissipation spectrum (y(+)(kp)) are investigated
      experimentally in the low Reynolds number (R(theta)<5000) zero-pressure-gradient
      turbulent boundary layers. These peaks are scaled by the relation
      y(+)(kp)=2(u(*)delta/nu)(1/2)=2R(1/2)(*), where u(*) is friction velocity and
      delta is the boundary layer thickness. They are located close to the peak
      positions of the Reynolds shear stress (y(+)(p)), that is, y(+)(kp) approximately
      equal to y(+)(p). This result predicts that the small-scale structures residing
      in high-energy dissipation regions concentrate around y(+)(p).

PMID- 11969719
TI  - Percolation-enhanced nonlinear scattering from metal-dielectric composites.
AB  - It is shown that large percolation-enhanced nonlinear scattering occurs in metal
      dielectric random composites near the percolation threshold. The enhancement is
      due to giant local electric field fluctuations that are extremely inhomogeneous
      and consist of spatially separated sharp peaks, "hot" spots, where the local
      field is greater by many orders of magnitude than the applied field.

PMID- 11969720
TI  - Solidity of viscous liquids. II. Anisotropic flow events.
AB  - Recent findings on displacements in the surroundings of isotropic flow events in
      viscous liquids [Phys. Rev. E 59, 2458 (1999)] are generalized to the anisotropic
      case. Also, it is shown that a flow event is characterized by a dimensionless
      number reflecting the degree of anisotropy.

PMID- 11969721
TI  - Output of a neuronal population code.
AB  - In the population coding framework, we consider how the response distributions
      affect output distribution. A general theory for the output of neuronal
      population code is presented when the spike train is a renewal process. Under a
      given condition on the response distribution, the most probable value of the
      output distribution is the center of input-preferred values, whereas in the other
      cases the most improbable value of the output distribution is the center of input
      preferred values or there are no most probable states. Depending on the exact
      form of the response distributions, the variance of the output distributions can
      either enlarge or reduce the tuning width of the tuning curves.

PMID- 11969722
TI  - Generation of soliton oscillations in nonlinear quadratic materials.
AB  - We show analytically and numerically that the generation of long-lasting soliton
      oscillations in resonant chi(2) optical materials possesses a threshold for the
      amplitude of a fundamental wave. The persistent oscillations of solitary waves
      reported by Etrich et al. [Phys. Rev. E 54, 4321 (1996)] are found to appear for
      finite values of the wave amplitude.

PMID- 11969723
TI  - Efficiency of Brownian heat engines.
AB  - We study the efficiency of one-dimensional thermally driven Brownian ratchets or
      heat engines. We identify and compare the three basic setups characterized by the
      type of the connection between the Brownian particle and the two heat reservoirs:
      (i) simultaneous, (ii) alternating in time, and (iii) position dependent. We make
      a clear distinction between the heat flow via the kinetic and the potential
      energy of the particle, and show that the former is always irreversible and it is
      only the third setup where the latter is reversible when the engine works
      quasistatically. We also show that in the third setup the heat flow via the
      kinetic energy can be reduced arbitrarily, proving that even for microscopic heat
      engines there is no fundamental limit of the efficiency lower than that of a
      Carnot cycle.

PMID- 11969724
TI  - Spatial multistability and nonvariational effects.
AB  - We investigate the phenomenon of spatial multistability of fronts in thin
      bistable systems and stress the important role played by the absence of a
      variational principle. Nonvariational effects allow, for instance, two different
      immobilized fronts to coexist. The morphological instability of the corresponding
      nucleating solution can then lead, even in the absence of any diffusive
      instability, to nontrivial patterns in the depth of one-side-fed reactors.

PMID- 11969725
TI  - Universal asymptotic eigenvalue distribution of density matrices and corner
      transfer matrices in the thermodynamic limit.
AB  - We study the asymptotic behavior of the eigenvalue distribution of the corner
      transfer matrix (M(CTM)) and the density matrix (M(DM)) in the density-matrix
      renormalization group. We utilize the relationship M(DM)=M(4)(CTM), which holds
      for noncritical systems in the thermodynamic limit. We derive the exact and
      universal asymptotic form of the M(DM) eigenvalue distribution for a class of
      integrable models in the massive regime. For nonintegrable models, the universal
      asymptotic form is also verified by numerical renormalization group calculations.

PMID- 11969726
TI  - Scale invariance and intermittency in a creep-slip model of earthquake faults.
AB  - The dynamics of a generalization of the one-dimensional, spatially discretized
      Burridge-Knopoff model (slider-block model) is investigated numerically. Plastic
      deformation of the fault interface is considered in addition to rigid sliding
      (creep-slip model). The event-size distribution exhibits scale invariance
      (beta=1.5), as does the power spectral density of the intermittent time series of
      the spatially averaged sliding rate (sigma=1.3). A diffusive cellular automaton
      model that reproduces the algebraic correlations in the event-size distribution
      in the presence of dissipation is proposed.

PMID- 11969727
TI  - Effect of correlation between additive and multiplicative noises on the
      activation from a double well.
AB  - We study the thermal activation problem of a bistable system driven by correlated
      additive and multiplicative noises by means of numerical simulation. We find that
      in the colored noise case the suppression effect of the positive correlation
      decreases and finally is released as the autocorrelation time tau of the colored
      noise grows. When tau is large enough, negative correlation becomes more
      suppressive than the positive correlation. Such phenomena are ascribed to the
      collaboration between noises as well as the memory effect of the multiplicative
      colored noise.

PMID- 11969728
TI  - Resistance of Feynman diagrams and the percolation backbone dimension.
AB  - We present an alternative view of Feynman diagrams for the field theory of random
      resistor networks, in which the diagrams are interpreted as being resistor
      networks themselves. This simplifies the field theory considerably as we
      demonstrate by calculating the fractal dimension D(B) of the percolation backbone
      to three loop order. Using renormalization group methods we obtain
      D(B)=2+epsilon/21-172epsilon(2)/9261+2epsilon(3)[-74 639+22 680zeta(3)]/4 084
      101, where epsilon=6-d with d being the spatial dimension and zeta(3)=1.202
      057... .

PMID- 11969729
TI  - Robustness of supersensitivity to small signals in nonlinear dynamical systems.
AB  - Nonlinear dynamical systems possessing an invariant subspace can display
      interesting dynamical behavior, such as on-off intermittency and bubbling. This
      Rapid Communication shows that a class of such systems has amazing features of
      (1) supersensitivity to small input signals and (2) robustness of the
      supersensitivity in the presence of noise. These features make the systems very
      promising as small signal detectors.

PMID- 11969730
TI  - Observability of lag synchronization of coupled chaotic oscillators.
AB  - Lag synchronization is a recently discovered theoretical phenomenon where the
      dynamical variables of two coupled, nonidentical chaotic oscillators are
      synchronized with a time delay relative to each other. We investigate
      experimentally and numerically to what extent lag synchronization can be observed
      in physical systems where noise is inevitable. Our measurements and numerical
      computation suggest that lag synchronization is typically destroyed when the
      noise level is comparable to the amount of average system mismatch. At small
      noise levels, lag synchronization occurs in an intermittent fashion.

PMID- 11969731
TI  - Three-dimensional organization of electrical turbulence in the heart.
AB  - Three-dimensional organization of electrical turbulence that is induced via the
      phenomenon of spiral breakup is studied in a computer model of the heart, which
      includes realistic ventricular geometries and cardiac anisotropy. We find
      filaments of rotors during the turbulence and study their number and length as a
      function of the heart size. We perform a dimensional analysis of turbulence.

PMID- 11969732
TI  - Spontaneous patterning of quantum dots at the air-water interface.
AB  - Nanoparticles deposited at the air-water interface are observed to form circular
      domains at low density and stripes at higher density. We interpret these patterns
      as equilibrium phenomena produced by a competition between an attraction and a
      longer-ranged repulsion. Computer simulations of a generic pair potential with
      attractive and repulsive parts of this kind, reproduce both the circular and
      stripe patterns. Such patterns have a potential use in nanoelectronic
      applications.

PMID- 11969733
TI  - Stress in conic piles determined by a centrifuge experiment: breakdown of scaling
      hypothesis.
AB  - It is found experimentally that vertical-stress field in a conic pile depends on
      gravity level, building process, and loading story. For instance, a conic pile
      with inclined strata does exhibit a minimum of stress in the center, whereas
      conic pile with horizontal strata does not; both piles exhibit an arching effect,
      which increases with gravity. This questions the assumptions of radius stress
      field scaling. Amplitude of the stress dip is found to be 10%, which is much
      smaller than what was found in previous experiments.

PMID- 11969734
TI  - Fast coarsening in unstable epitaxy with desorption.
AB  - Homoepitaxial growth is unstable towards the formation of pyramidal mounds when
      interlayer transport is reduced due to activation barriers to hopping at step
      edges. Simulations of a lattice model and a continuum equation show that a small
      amount of desorption dramatically speeds up the coarsening of the mound array,
      leading to coarsening exponents between 1/3 and 1/2. The underlying mechanism is
      the faster growth of larger mounds due to their lower evaporation rate.

PMID- 11969736
TI  - Using weak impulses to suppress traveling waves in excitable media.
AB  - Here we propose mechanisms for suppressing non-steady-state motions--propagating
      pulses, spiral waves, spiral-wave chaos--in excitable media. Our approach is
      based on two points: (1) excitable media are multistable; and (2) traveling waves
      in excitable media can be separated into fast and slow motions, which can be
      considered independently. We show that weak impulses can be used to change the
      values of the slow variable at the front and back of a traveling wave, which
      leads to wave front and wave back velocities that are different from each other.
      This effect can destabilize the traveling wave, resulting in a transition to the
      rest state.

PMID- 11969735
TI  - Fisher-based thermodynamics: its Legendre transform and concavity properties.
AB  - It is shown that the Legendre-transform structure of thermodynamics can be
      replicated without any change if one replaces the entropy S by Fisher's
      information measure I. Also, the important thermodynamic property of concavity is
      shown to be obeyed by I. By this use of the Fisher information measure we develop
      a thermodynamics that seems to be able to treat equilibrium and nonequilibrium
      situations in a manner entirely similar to the conventional one.

PMID- 11969737
TI  - Continuous phase transition in a spin-glass model without time-reversal symmetry.
AB  - We investigate the phase transition in a strongly disordered short-range three
      spin interaction model characterized by the absence of time-reversal symmetry in
      the Hamiltonian. In the mean-field limit the model is well described by the Adam
      Gibbs-DiMarzio scenario for the glass transition; however, in the short-range
      case this picture turns out to be modified. The model presents a finite
      temperature continuous phase transition characterized by a divergent spin-glass
      susceptibility and a negative specific-heat exponent. We expect the nature of the
      transition in this three-spin model to be the same as the transition in the
      Edwards-Anderson model in a magnetic field, with the advantage that the strong
      crossover effects present in the latter case are absent.

PMID- 11969738
TI  - Recent results on multiplicative noise.
AB  - Recent developments in the analysis of Langevin equations with multiplicative
      noise (MN) are reported. In particular, we (i) present numerical simulations in
      three dimensions showing that the MN equation exhibits, like the Kardar-Parisi
      Zhang (KPZ) equation, both a weak coupling fixed point and a strong coupling
      phase, supporting the proposed relation between MN and KPZ; (ii) present a
      dimensional and mean-field analysis of the MN equation to compute critical
      exponents; (iii) show that the phenomenon of the noise-induced ordering
      transition associated with the MN equation appears only in the Stratonovich
      representation and not in the Ito one; and (iv) report the presence of a first
      order-like phase transition at zero spatial coupling, supporting the fact that
      this is the minimum model for noise-induced ordering transitions.

PMID- 11969739
TI  - Exact solution of the asymmetric exclusion model with particles of arbitrary
      size.
AB  - A generalization of the simple exclusion asymmetric model is introduced. In this
      model an arbitrary mixture of molecules with distinct sizes s=0,1,2, ..., in
      units of lattice space, diffuses asymmetrically on the lattice. A related surface
      growth model is also presented. Variations of the distribution of the molecules
      sizes may change the excluded volume almost continuously. We solve the model
      exactly through the Bethe ansatz and the dynamical critical exponent z is
      calculated from the finite-size corrections of the mass gap of the related
      quantum chain. Our results show that for an arbitrary distribution of molecules,
      the dynamical critical behavior is on the Kardar-Parizi-Zhang universality.

PMID- 11969740
TI  - Random deposition of two annihilating species in the (1+1) dimension.
AB  - We present simulation results for the one-dimensional random deposition of two
      annihilating species A and B, falling with probabilities p and q (p+q=1), which
      then react to produce an inert product, i.e., A+B-->0. Two different annihilation
      rules are defined: top annihilation and nearest-neighbor annihilation (NNA),
      leading to distinct scaling behaviors. In particular, the values of the scaling
      exponents for NNA are found to be dependent on probability p, suggesting
      different universality classes.

PMID- 11969741
TI  - Quantum kinetics and thermalization in a particle bath model.
AB  - We study the dynamics of relaxation and thermalization in an exactly solvable
      model of a particle interacting with a harmonic oscillator bath. Our goal is to
      understand the effects of non-Markovian processes on the relaxational dynamics
      and to compare the exact evolution of the distribution function with approximate
      Markovian and non-Markovian quantum kinetics. There are two different cases that
      are studied in detail: (i) a quasiparticle (resonance) when the renormalized
      frequency of the particle is above the frequency threshold of the bath and (ii) a
      stable renormalized "particle" state below this threshold. The time evolution of
      the occupation number for the particle is evaluated exactly using different
      approaches that yield to complementary insights. The exact solution allows us to
      investigate the concept of the formation time of a quasiparticle and to study the
      difference between the relaxation of the distribution of bare particles and that
      of quasiparticles. For the case of quasiparticles, the exact occupation number
      asymptotically tends to a statistical equilibrium distribution that differs from
      a simple Bose-Einstein form as a result of off-shell processes whereas in the
      stable particle case, the distribution of particles does not thermalize with the
      bath. We derive a non-Markovian quantum kinetic equation which resums the
      perturbative series and includes off-shell effects. A Markovian approximation
      that includes off-shell contributions and the usual Boltzmann equation (energy
      conserving) are obtained from the quantum kinetic equation in the limit of wide
      separation of time scales upon different coarse-graining assumptions. The
      relaxational dynamics predicted by the non-Markovian, Markovian, and Boltzmann
      approximations are compared to the exact result. The Boltzmann approach is seen
      to fail in the case of wide resonances and when threshold and renormalization
      effects are important.

PMID- 11969742
TI  - Phase transitions in open quantum systems.
AB  - We consider the behavior of open quantum systems through the dependence of the
      coupling to one decay channel by introducing the coupling parameter alpha, which
      is proportional to the average degree of overlapping. Under critical conditions,
      a reorganization of the spectrum takes place that creates a bifurcation of the
      time scales with respect to the lifetimes of the resonance states. We derive
      analytically the conditions under which the reorganization process can be
      understood as a second-order phase transition and illustrate our results by
      numerical investigations. The conditions are fulfilled, e.g., for a uniform
      picket-fence level distribution with equal coupling of the states to the
      continuum. Energy dependencies within the system are included. We consider also
      the case of an unfolded Gaussian orthogonal ensemble and of a spectrum bounded
      from below. In all these cases, the reorganization of the spectrum occurs at the
      critical value alpha(crit) of the control parameter globally over the whole
      energy range of the spectrum. All states act cooperatively.

PMID- 11969743
TI  - Statistical mechanics of image restoration and error-correcting codes.
AB  - We develop a statistical-mechanical formulation for image restoration and error
      correcting codes. These problems are shown to be equivalent to the Ising spin
      glass with ferromagnetic bias under random external fields. We prove that the
      quality of restoration/decoding is maximized at a specific set of parameter
      values determined by the source and channel properties. For image restoration in
      a mean-field system a line of optimal performance is shown to exist in the
      parameter space. These results are illustrated by solving exactly the infinite
      range model. The solutions enable us to determine how precisely one should
      estimate unknown parameters. Monte Carlo simulations are carried out to see how
      far the conclusions from the infinite-range model are applicable to the more
      realistic two-dimensional case in image restoration.

PMID- 11969744
TI  - Exact solutions of some urn models of relaxation in glassy dynamics.
AB  - We consider two simple models, called "urn models," for a general N-ball, M-urn
      problem. These models find applications in the study of relaxation in glassy
      dynamics. We obtain exact analytical results in these two cases for the average
      relaxation time tau to reach the ground state. In model I we also obtain the
      functional dependence of tau for large N, and in model II we obtain an asymptotic
      (N-->infinity) dependence of tau as a function of the number of urns M.

PMID- 11969745
TI  - Cellular automaton models of driven diffusive Frenkel-Kontorova-type systems.
AB  - Three cellular automaton models of increasing complexity are introduced to model
      driven diffusive systems related to the generalized Frenkel-Kontorova (FK) models
      recently proposed by Braun et al. [Phys. Rev. E 58, 1311 (1998)]. The models are
      defined in terms of parallel updating rules. Simulation results are presented for
      these models. The features are qualitatively similar to those models defined
      previously in terms of sequentially updating rules. Essential features of the FK
      model such as phase transitions, jamming due to atoms in the immobile state, and
      hysteresis in the relationship between the fraction of atoms in the running state
      and the bias field are captured. Formulating in terms of parallel updating rules
      has the advantage that the models can be treated analytically by following the
      time evolution of the occupation on every site of the lattice. Results of this
      analytical approach are given for the two simpler models. The steady state
      properties are found by studying the stable fixed points of a closed set of
      dynamical equations obtained within the approximation of retaining spatial
      correlations only up to two nearest-neighboring sites. Results are found to be in
      good agreement with numerical data.

PMID- 11969746
TI  - Fluctuation theorem for stochastic systems.
AB  - The fluctuation theorem describes the probability ratio of observing trajectories
      that satisfy or violate the second law of thermodynamics. It has been proved in a
      number of different ways for thermostatted deterministic nonequilibrium systems.
      In the present paper we show that the fluctuation theorem is also valid for a
      class of stochastic nonequilibrium systems. The theorem is therefore not reliant
      on the reversibility or the determinism of the underlying dynamics. Numerical
      tests verify the theoretical result.

PMID- 11969747
TI  - Thermodynamics of boson and fermion systems with fractal distribution functions.
AB  - Starting with the fractal-inspired distribution functions for Maxwell-Boltzmann,
      Bose-Einstein, and Fermi systems, as reported by Buyukkilic and Demirhan, we
      obtain the corresponding probability distributions and study their thermodynamic
      behavior. We compare our results with those corresponding to ideal gases (q=1)
      and Bose-Einstein and Fermi systems with quantum group symmetry. In particular,
      we show that the Hamiltonian that gives the Bose-Einstein generalized
      distribution function can be interpreted as a q deformation of the ideal gas
      Hamiltonian.

PMID- 11969748
TI  - Anomalous jumping in a double-well potential.
AB  - Noise-induced jumping between metastable states in a potential depends on the
      structure of the noise. For an alpha-stable noise, jumping triggered by single
      extreme events contributes to the transition probability. This is also called
      Levy flights and might be of importance in triggering sudden changes in
      geophysical flow and perhaps even climatic changes. The steady-state statistics
      is also influenced by the noise structure leading to a non-Gibbs distribution for
      an alpha-stable noise.

PMID- 11969749
TI  - Soliton and kink jams in traffic flow with open boundaries.
AB  - Soliton density wave is investigated numerically and analytically in the optimal
      velocity model (a car-following model) of a one-dimensional traffic flow with
      open boundaries. Soliton density wave is distinguished from the kink density
      wave. It is shown that the soliton density wave appears only at the threshold of
      occurrence of traffic jams. The Korteweg-de Vries (KdV) equation is derived from
      the optimal velocity model by the use of the nonlinear analysis. It is found that
      the traffic soliton appears only near the neutral stability line. The soliton
      solution is analytically obtained from the perturbed KdV equation. It is shown
      that the soliton solution obtained from the nonlinear analysis is consistent with
      that of the numerical simulation.

PMID- 11969750
TI  - Analytic approach to the critical density in cellular automata for traffic flow.
AB  - The jamming transition in the stochastic traffic cellular automaton of Nagel and
      Schreckenberg [J. Phys. I 2, 2221 (1992)] is examined. We argue that most
      features of the transition found in the deterministic limit do not persist in the
      presence of noise, and suggest instead to define the transition to take place at
      that critical density rho(c) at which a large initial jam just fails to dissolve.
      We show that rho(c)=v(J)/(v(J)+v(F)), where v(F) is the velocity of
      noninteracting vehicles and v(J) is the speed of the dissolution wave moving into
      the jam. An approximate analytic calculation of v(J) in the framework of a simple
      renormalization scheme is presented, which explicitly displays the effect of the
      interaction between vehicles during the acceleration stage of the Nagel
      Schreckenberg rules with maximum velocity v(max)>1. The analytic prediction is
      compared to numerical simulations. We find a remarkable correspondence between
      the analytic expression for v(J) and a phase diagram obtained numerically by
      Lubeck et al.

PMID- 11969751
TI  - Exact results for deterministic cellular automata traffic models.
AB  - We present a rigorous derivation of the flow at arbitrary time in a deterministic
      cellular automaton model of traffic flow. The derivation employs regularities in
      preimages of blocks of zeros, reducing the problem of preimage enumeration to a
      well-known lattice path counting problem. Assuming infinite lattice size and
      random initial configuration, the flow can be expressed in terms of generalized
      hypergeometric function. We show that the steady-state limit agrees with
      previously published results.

PMID- 11969752
TI  - Dissipative multistate systems in the scaling limit.
AB  - The dynamics of dissipative multistate systems is studied using integral
      equations that are derived within the framework of the path integral-formulation
      of quantum mechanics. As an illustrative example we study a 5-state system
      coupled to a harmonic reservoir with an Ohmic spectral density with a high cutoff
      frequency. The dominant exchange mechanism determining the dynamics as well as
      the range of validity of different approximations to the influence functional are
      investigated. Besides depending on temperature and the strength of the system
      bath coupling, both the exchange mechanism and the accuracy of different
      approximations to the influence functional depend on the state in which the
      system is initially prepared.

PMID- 11969753
TI  - Dynamical scaling: the two-dimensional XY model following a quench.
AB  - To sensitively test scaling in the two-dimensional XY model quenched from high
      temperatures into the ordered phase, we study the difference between measured
      correlations and the (scaling) results of a Gaussian-closure approximation. We
      also directly compare various length scales. All of our results are consistent
      with dynamical scaling and an asymptotic growth law L approximately
      (t/ln[t/t(0)])(1/2), though with a time scale t(0) that depends on the length
      scale in question. We then reconstruct correlations from the minimal-energy
      configuration consistent with the vortex positions, and find them significantly
      different from the "natural" correlations - though both scale with L. This
      indicates that both topological (vortex) and nontopological "spin-wave"
      contributions to correlations are relevant arbitrarily late after the quench. We
      also present a consistent definition of dynamical scaling applicable more
      generally, and emphasize how to generalize our approach to other quenched systems
      where dynamical scaling is in question. Our approach directly applies to planar
      liquid-crystal systems.

PMID- 11969754
TI  - Overdamped sine-Gordon kink in a thermal bath.
AB  - We study sine-Gordon kink diffusion at finite temperature in the overdamped
      limit. By means of a general perturbative approach, we calculate the first- and
      second-order (in temperature) contributions to the diffusion coefficient. We
      compare our analytical predictions with numerical simulations. The good agreement
      allows us to conclude that, up to temperatures where kink-antikink nucleation
      processes cannot be neglected, a diffusion constant linear and quadratic in
      temperature gives a very accurate description of the diffusive motion of the
      kink. The quadratic temperature dependence is shown to stem from the interaction
      with the phonons. In addition, we calculate and compute the average value <
      phi(x,t)> of the wave function as a function of time, and show that its width
      grows with square root of t. We discuss the interpretation of this finding and
      show that it arises from the dispersion of the kink center positions of
      individual realizations which all keep their width.

PMID- 11969755
TI  - Thermodynamics of quantum dissipative many-body systems.
AB  - We consider quantum nonlinear many-body systems with dissipation described within
      the Caldeira-Leggett model, i.e., by a nonlocal action in the path integral for
      the density matrix. Approximate classical-like formulas for thermodynamic
      quantities are derived for the case of many degrees of freedom, with general
      kinetic and dissipative quadratic forms. The underlying scheme is the pure
      quantum self-consistent harmonic approximation (PQSCHA), equivalent to the
      variational approach by the Feynman-Jensen inequality with a suitable quadratic
      nonlocal trial action. A low-coupling approximation permits us to get manageable
      PQSCHA expressions for quantum thermal averages with a classical Boltzmann factor
      involving an effective potential and an inner Gaussian average that describes the
      fluctuations originating from the interplay of quanticity and dissipation. The
      application of the PQSCHA to a quantum phi(4) chain with Drude-like dissipation
      shows nontrivial effects of dissipation, depending upon its strength and
      bandwidth.

PMID- 11969756
TI  - Theory of spike spiral waves in a reaction-diffusion system.
AB  - We discovered a type of spiral wave solutions in reaction-diffusion systems-
      spike spiral wave, which significantly differs from the spiral waves observed in
      the models of FitzHugh-Nagumo type. We present an asymptotic theory of these
      waves in the Gray-Scott model [Chem. Sci. Eng. 38, 29 (1983)]. We derive the
      kinematic relations describing the shape of this spiral, and find the dependence
      of its main parameters on the control parameters. The theory does not rely on the
      specific features of the Gray-Scott model and thus is expected to be applicable
      to a broad range of reaction-diffusion systems.

PMID- 11969757
TI  - Lifetime statistics for a Bloch particle in ac and dc fields.
AB  - We study the statistics of the Wigner delay time and resonance width for a Bloch
      particle in ac and dc fields in the regime of quantum chaos. It is shown that
      after appropriate rescaling the distributions of these quantities have a
      universal character predicted by the random matrix theory of chaotic scattering.

PMID- 11969758
TI  - Universality and self-similarity of an energy-constrained sandpile model with
      random neighbors.
AB  - We study an energy-constrained sandpile model with random neighbors. The critical
      behavior of the model is in the same universality class as the mean-field self
      organized criticality sandpile. The critical energy E(c) depends on the number of
      neighbors n for each site, but the various exponents are independent of n. A self
      similar structure with n-1 major peaks is developed for the energy distribution
      p(E) when the system approaches its stationary state. The avalanche dynamics
      contributes to the major peaks appearing at E(p(k))=2k/(2n-1) with k=1,2,...,n-1,
      while the fine self-similar structure is a natural result of the way the system
      is disturbed.

PMID- 11969759
TI  - Thermodynamically reversible generalization of diffusion limited aggregation.
AB  - We introduce a lattice gas model of cluster growth via the diffusive aggregation
      of particles in a closed system obeying a local, deterministic, microscopically
      reversible dynamics. This model roughly corresponds to placing the irreversible
      diffusion limited aggregation model (DLA) in contact with a heat bath. Particles
      release latent heat when aggregating, while singly connected cluster members can
      absorb heat and evaporate. The heat bath is initially empty, hence we observe the
      flow of entropy from the aggregating gas of particles into the heat bath, which
      is being populated by diffusing heat tokens. Before the population of the heat
      bath stabilizes, the cluster morphology (quantified by the fractal dimension) is
      similar to a standard DLA cluster. The cluster then gradually anneals, becoming
      more tenuous, until reaching configurational equilibrium when the cluster
      morphology resembles a quenched branched random polymer. As the microscopic
      dynamics is invertible, we can reverse the evolution, observe the inverse flow of
      heat and entropy, and recover the initial condition. This simple system provides
      an explicit example of how macroscopic dissipation and self-organization can
      result from an underlying microscopically reversible dynamics. We present a
      detailed description of the dynamics for the model, discuss the macroscopic
      limit, and give predictions for the equilibrium particle densities obtained in
      the mean field limit. Empirical results for the growth are then presented,
      including the observed equilibrium particle densities, the temperature of the
      system, the fractal dimension of the growth clusters, scaling behavior, finite
      size effects, and the approach to equilibrium. We pay particular attention to the
      temporal behavior of the growth process and show that the relaxation to the
      maximum entropy state is initially a rapid nonequilibrium process, then
      subsequently it is a quasistatic process with a well defined temperature.

PMID- 11969760
TI  - Site percolation thresholds for Archimedean lattices.
AB  - Precise thresholds for site percolation on eight Archimedean lattices are
      determined by the hull-walk gradient-percolation simulation method, with the
      results p(c)=0.697 043, honeycomb or (6(3)), 0.807 904 (3,12(2)), 0.747 806
      (4,6,12), 0.729 724 (4,8(2)), 0.579 498 (3(4),6), 0.621 819 (3,4,6,4), 0.550 213
      (3(3),4(2)), and 0.550 806 (3(2),4,3,4), with errors of about +/- 3 x 10(-6).
      [The remaining Archimedean lattices are the square (4(4)), triangular (3(6)), and
      Kagome (3,6,3,6), for which p(c) is already known exactly or to a high degree of
      accuracy.] The numerical result for the (3,12(2)) lattice is consistent with the
      exact value [1-2 sin(pi/18)](1/2). The values of p(c) for all 11 Archimedean
      lattices, as well as a number of nonuniform lattices, are found to be well
      correlated by a nearly linear function of a generalized Scher-Zallen filling
      factor. This correlation is much more accurate than recently proposed
      correlations based solely upon coordination number.

PMID- 11969761
TI  - Synchronization of noisy systems by stochastic signals.
AB  - We study, in terms of synchronization, the nonlinear response of noisy bistable
      systems to a stochastic external signal, represented by Markovian dichotomic
      noise. We propose a general kinetic model which allows us to conduct a full
      analytical study of the nonlinear response, including the calculation of cross
      correlation measures, the mean switching frequency, and synchronization regions.
      Theoretical results are compared with numerical simulations of a noisy overdamped
      bistable oscillator. We show that dichotomic noise can instantaneously
      synchronize the switching process of the system. We also show that
      synchronization is most pronounced at an optimal noise level-this effect connects
      this phenomenon with aperiodic stochastic resonance. Similar synchronization
      effects are observed for a stochastic neuron model stimulated by a stochastic
      spike train.

PMID- 11969762
TI  - Nonlocal Kardar-Parisi-Zhang equation with spatially correlated noise.
AB  - The effects of spatially correlated noise on a phenomenological equation
      equivalent to a nonlocal version of the Kardar-Parisi-Zhang (KPZ) equation are
      studied via the dynamic renormalization group (DRG) techniques. The correlated
      noise coupled with the long ranged nature of interactions prove the existence of
      different phases in different regimes, giving rise to a range of roughness
      exponents defined by their corresponding critical dimensions. Finally self
      consistent mode analysis is employed to compare the non-KPZ exponents obtained as
      a result of the long-range interactions with the DRG results.

PMID- 11969763
TI  - Stationary space-periodic structures with equal diffusion coefficients.
AB  - The paper investigates a chemical reaction-diffusion model in an open flow
      system. It is shown that such a system may, with particular boundary conditions,
      exhibit stationary space-periodic structures even in the case of equal diffusion
      coefficients. This is confirmed through numerical simulations.

PMID- 11969764
TI  - Diffusion on curved, periodic surfaces.
AB  - We present a simulation algorithm for a diffusion on a curved surface given by
      the equation phi(r)=0. The algorithm is tested against analytical results known
      for diffusion on a cylinder and a sphere, and applied to the diffusion on the P,
      D, and G periodic nodal surfaces. It should find application in an interpretation
      of two-dimensional exchange NMR spectroscopy data of diffusion on biological
      membranes.

PMID- 11969765
TI  - Nonlinear dynamics of giant resonances in atomic nuclei.
AB  - The dynamics of monopole giant resonances in nuclei is analyzed in the time
      dependent relativistic mean-field model. The phase spaces of isoscalar and
      isovector collective oscillations are reconstructed from the time series of
      dynamical variables that characterize the proton and neutron density
      distributions. The analysis of the resulting recurrence plots and correlation
      dimensions indicates regular motion for the isoscalar mode, and chaotic dynamics
      for the isovector oscillations. Information-theoretic functionals identify and
      quantify the nonlinear dynamics of giant resonances in quantum systems that have
      spatial as well as temporal structure.

PMID- 11969767
TI  - Dynamical ansatz for path integrals and nonperturbative trace formulas.
AB  - It is shown that a recently discovered representation of the Green's function is
      equivalent to a certain "dynamical ansatz" for the corresponding path integral,
      which brings about a convenient method of nonperturbative approximations. Based
      on this observation, a set of nonperturbative approximations to the trace of the
      Green's function is established.

PMID- 11969766
TI  - Extracting messages masked by chaotic signals of time-delay systems.
AB  - We show how to extract messages masked by a chaotic signal of a time-delay system
      with very high dimensions and many positive Lyapunov exponents. Using a special
      embedding coordinate, the infinite-dimensional phase space of the time-delay
      system is projected onto a special three-dimensional space, which enables us to
      identify the time delay of the system from the transmitted signal and reconstruct
      the chaotic dynamics to unmask the hidden message successfully. The message
      extraction procedure is illustrated by simulations with the Mackey-Glass time
      delay system for two types of masking schemes and different kinds of messages.

PMID- 11969768
TI  - Semiclassical interaction of moving two-level atoms with a cavity field: from
      integrability to Hamiltonian chaos.
AB  - The dynamics of an ensemble of two-level atoms moving through a single-mode
      lossless cavity is investigated in the semiclassical and rotating-wave
      approximations. The dynamical system for the expectation values of the atomic and
      field observables is considered as a perturbation to one of the following
      integrable versions: (i) a model with atoms moving through a spatially
      inhomogeneous resonant field, and (ii) a model with atoms interacting with a
      nonresonant eigenmode which is assumed to be homogeneous on the cavity size. We
      find the general exact solutions for both the models and show that they contain
      special solutions describing a coherent effect of population and radiation
      trapping. Using the Melnikov method, we prove analytically transverse
      intersections of stable and unstable manifolds of a hyperbolic fixed point under
      a small modulation of the vacuum Rabi frequency. These intersections are believed
      to provide the Smale horseshoe mechanism of Hamiltonian chaos. The analytical
      results are accompanied with direct computation of topographical maps of maximal
      Lyapunov exponents that give a representative image of regularity and chaos in
      the atom-field system in different ranges of its control parameters--the
      frequency detuning, the number, and the velocity of atoms.

PMID- 11969769
TI  - Measure-theoretical properties of the unstable foliation of two-dimensional
      differentiable area-preserving systems.
AB  - This article analyzes in detail the statistical and measure-theoretical
      properties of the nonuniform stationary measure, referred to as the w-invariant
      measure, associated with the spatial length distribution of the integral
      manifolds of the unstable invariant foliation in two-dimensional differentiable
      area-preserving systems. The analysis is developed starting from a sequence of
      analytical approximations for the associated density. These approximations are
      related to the properties of the Jacobian matrix of the nth iteration of a
      Poincare map. The w-invariant measure plays a fundamental role in the study of
      transport phenomena in laminar-chaotic fluid-mixing systems, for which it
      furnishes the asymptotic invariant distribution of intermaterial contact length
      between two fluids. The w-invariant measure turns out to be singular and exhibits
      multifractal features. Its associated density displays local self-similarity in
      an epsilon neighborhood of hyperbolic periodic points. The cancellation exponent
      of the signed measure associated with the w measure by attaching at each point
      the direction of the field of the asymptotic unstable eigenvectors is also
      analyzed. The only case for which the w-invariant measure is absolutely
      continuous is given by the conjugation of hyperbolic toral automorphisms with a
      linear automorphism. The connections with the statistical properties, and in
      particular with the stretching dynamics, are addressed in detail.

PMID- 11969770
TI  - Computing with distributed chaos.
AB  - We describe and discuss in detail some recent results by Sinha and Ditto [Phys.
      Rev. Lett. 81, 2156 (1998)] demonstrating the capacity of a lattice of threshold
      coupled chaotic maps to perform computations. Such systems are shown to emulate
      logic gates, encode numbers, and perform specific arithmetic operations, such as
      addition and multiplication, as well as yield more specialized operations such as
      the calculation of the least common multiplier of a sequence of numbers.
      Furthermore, we extend the scheme to multidimensional continuous time dynamics,
      in particular to a system relevant to chaotic lasers.

PMID- 11969771
TI  - Box-counting dimension without boxes: computing D0 from average expansion rates.
AB  - We propose an efficient iterative scheme for calculating the box-counting
      (capacity) dimension of a chaotic attractor in terms of its average expansion
      rates. Similar to the Kaplan-Yorke conjecture for the information dimension, this
      scheme provides a connection between a geometric property of a strange set and
      its underlying dynamical properties. Our conjecture is demonstrated analytically
      with an exactly solvable two-dimensional hyperbolic map, and numerically with a
      more complicated higher-dimensional nonhyperbolic map.

PMID- 11969772
TI  - Noise-amplitude dependence of the invariant density for noisy, fully chaotic one
      dimensional maps.
AB  - We present some analytic, nonperturbative results for the invariant density
      rho(x) for noisy one-dimensional maps at fully developed chaos. Under periodic
      boundary conditions, the Fourier expansion method is used to show precisely how
      noise makes rho(x) absolutely continuous and smooths it out. Simple solvable
      models are used to illustrate the explicit dependence of rho(x) on the amplitude
      eta of the noise distribution, all the way from the case of zero noise (eta-->0)
      to the completely noise-dominated limit (eta=1).

PMID- 11969773
TI  - Correlation decay in quantum chaotic billiards with bulk or surface disorder.
AB  - We study the decay properties of correlation functions in quantum billiards with
      surface or bulk disorder. The quantum system is modeled by means of a tight
      binding Hamiltonian with diagonal disorder, solved on LxL clusters of the square
      lattice. The correlation function is calculated by launching the system at t=0
      into a wave function of the regular (clean) system and following its time
      evolution. The results show that the correlation function decays exponentially
      with a characteristic correlation time (inverse of the Lyapunov exponent lambda).
      For small enough disorder the Lyapunov exponent is approximately given by the
      imaginary part of the self-energy induced by disorder. On the other hand, if the
      scaling of the Lyapunov exponent with L is investigated by keeping constant l/L,
      where l is the mean free path, the results show that lambda is proportional to
      1/L.

PMID- 11969776
TI  - Distribution of Husimi zeros in polygonal billiards.
AB  - The zeros of the Husimi function provide a minimal description of individual
      quantum eigenstates and their distribution is of considerable interest. We
      provide here a numerical study for pseudointegrable billiards which suggests that
      the zeros tend to diffuse over phase space in a manner reminiscent of chaotic
      systems but nevertheless contain a subtle signature of pseudointegrability. We
      also find that the zeros depend sensitively on the position and momentum
      uncertainties (Delta q and Delta p, respectively) with the classical
      correspondence best when Delta q = Delta p = square root of [Planck's
      constant/2]. Finally, short-range correlations seem to be well described by the
      Ginibre ensemble of complex matrices.

PMID- 11969774
TI  - Stabilization of unstable fixed points in the dynamics of a laser with feedback.
AB  - We report theoretical and experimental results on the stabilization of unstable
      steady states in a CO2 laser with feedback. Periodic and chaotic oscillations
      have been suppressed by means of a control loop consisting of a high-pass filter,
      known as washout filter. Although the filter characteristics are determined on
      the basis of linear analysis, taking into account the problem of robustness with
      respect to parameter changes, the present control strategy provides a large
      attractive domain in the phase space.

PMID- 11969775
TI  - Theory of oscillations in average crisis-induced transient lifetimes.
AB  - Analytical and numerical study of the roughly periodic oscillations emerging on
      the background of the well-known power law governing the scaling of the average
      lifetimes of crisis induced chaotic transients is presented. The explicit formula
      giving the amplitude of "normal" oscillations in terms of the eigenvalues of
      unstable orbits involved in the crisis is obtained using a simple geometrical
      model. We also discuss the commonly encountered situation when normal
      oscillations appear together with "anomalous" ones caused by the fractal
      structure of basins of attraction.

PMID- 11969777
TI  - Improving the false nearest neighbors method with graphical analysis.
AB  - We introduce a graphical presentation for the false nearest neighbors (FNN)
      method. In the original method only the percentage of false neighbors is computed
      without regard to the distribution of neighboring points in the time-delay
      coordinates. With this presentation it is much easier to distinguish
      deterministic chaos from noise. The graphical approach also serves as a tool to
      determine better conditions for detecting low-dimensional chaos, and to get a
      better understanding on the applicability of the FNN method.

PMID- 11969778
TI  - Large deviation properties of on-off intermittency.
AB  - The large deviation property of on-off intermittency is investigated by
      introducing a two-dimensional piecewise linear map, which can be mapped to an
      infinite Markov chain. It is shown that nonanalyticity, in the q-weighted average
      of the portion of time spent in burst state, appears as a second-order phase
      transition for an interval of control parameter with the bifurcation point of on
      off intermittency as its end point.

PMID- 11969779
TI  - Synchronization in chaotic Hamiltonian systems and a geophysical application.
AB  - This paper addresses the question of the rate of synchronization of two identical
      systems as a function of the inserting time interval Delta t between inserted
      variables of the driving system in the role of the same variables of the driven
      system in a simplified Hamiltonian system and its application to a simplified
      geophysical model. We start by analyzing the synchronization in a simplified two
      degree Hamiltonian system. The synchronization rate turns out to be a decreasing
      function of the inserting time interval Delta t up to a certain limit Delta t(o)
      where the process reverses and the synchronization rate becomes slower as the
      inserting frequency decreases. The key point of the analysis uses a second-order
      Taylor expansion of the system resolvent which indicates that synchronization
      rate is basically of order O(Delta t(2)) for small Delta t. The study is then
      extended to include a simplified geophysical system. A nonlinear one-dimensional
      shallow-water model on a periodic domain meant to represent a latitudinal circle
      around 45 degrees N is used. It is found that when the zonal wind is inserted,
      the maximum synchronization rate is obtained when the inserting time interval is
      approximately 4 h. When the meridional wind is inserted, it is obtained at
      slightly less than 4 h. It is shown, in particular, that the synchronization rate
      depends on the latitude (or the Coriolis parameter). A low-order simplified
      dynamical system derived from the one-dimensional shallow-water model is used to
      show that this optimum time interval Delta t(o) when the zonal wind and the
      geopotential, for example, are inserted varies approximately as square root of
      [2]/2 Omega sin phi to accuracy O(Delta t(3)). Analyses performed with a linear
      version of the shallow-water model reveal that this latter can be used to explain
      the observed convergence behavior in the nonlinear model. The only point is the
      choice of the stationary state for linearization purposes. It is then suggested
      that in more complicated geophysical systems, the closest stationary state to the
      climatology can be used to estimate the crossover point Delta t(o).

PMID- 11969780
TI  - Lyapunov exponents in unstable systems.
AB  - We investigate the dynamical behavior of unstable systems in the vicinity of the
      critical point associated with a liquid-gas phase transition. By considering a
      mean-field treatment, we first perform a linear analysis and discuss the
      instability growth times. Then, coming to complete Vlasov simulations, we
      investigate the role of nonlinear effects and calculate the Lyapunov exponents.
      As a main result, we find that near the critical point, the Lyapunov exponents
      exhibit a power-law behavior, with a critical exponent beta=0.5. This suggests
      that in thermodynamical systems the Lyapunov exponent behaves as an order
      parameter to signal the transition from the liquid to the gas phase.

PMID- 11969781
TI  - Semi-Poisson statistics and beyond.
AB  - Semi-Poisson statistics are shown to be obtained by removing every other number
      from a random sequence. Retaining every (r+1)th level we obtain a family of
      sequences, which we call daisy models. Their statistical properties coincide with
      those of Bogomolny's nearest-neighbor interaction Coulomb gas if the inverse
      temperature coincides with the integer r. In particular, the case r=2 reproduces
      closely the statistics of quasioptimal solutions of the traveling salesman
      problem.

PMID- 11969782
TI  - Localization and fluctuations in quantum kicked rotors.
AB  - We address the issue of fluctuations, about an exponential line shape, in a pair
      of one-dimensional kicked quantum systems exhibiting dynamical localization. An
      exact renormalization scheme establishes the fractal character of the
      fluctuations and provides a method to compute the localization length in terms of
      the fluctuations. In the case of a linear rotor, the fluctuations are independent
      of the kicking parameter k and exhibit self-similarity for certain values of the
      quasienergy. For given k, the asymptotic localization length is a good
      characteristic of the localized line shapes for all quasienergies. This is in
      stark contrast to the quadratic rotor, where the fluctuations depend upon the
      strength of the kicking and exhibit local "resonances." These resonances result
      in strong deviations of the localization length from the asymptotic value. The
      consequences are particularly pronounced when considering the time evolution of a
      packet made up of several quasienergy states.

PMID- 11969783
TI  - Finite statistical complexity for sofic systems.
AB  - We propose a measure of complexity for symbolic sequences, which is based on
      conditional probabilities, and captures computational aspects of complexity
      without the explicit construction of minimal deterministic finite automata (DFA).
      Moreover, if the sequence is obtained from a dynamical system through a suitable
      encoding and its equations of motion are known, we show how to estimate the
      regions of phase space that correspond to computational states with statistically
      equivalent futures (causal states).

PMID- 11969784
TI  - Rayleigh-Benard simulation using the gas-kinetic Bhatnagar-Gross-Krook scheme in
      the incompressible limit.
AB  - In this paper, a gas-kinetic Bhatnagar-Gross-Krook (BGK) model is constructed for
      the Rayleigh-Benard thermal convection in the incompressible flow limit, where
      the flow field and temperature field are described by two coupled BGK models.
      Since the collision times in the corresponding BGK models can be different, the
      Prandtl number can be changed to any value instead of a fixed Pr=1 in the
      original BGK model [P. L. Bhatnagar, E. P. Gross, and M. Krook, Phys. Rev. 94,
      511 (1954)]. The two-dimensional Rayleigh-Benard thermal convection is studied
      and numerical results are compared with theoretical ones as well as other
      simulation results.

PMID- 11969785
TI  - Linear response theory for thermodynamic properties.
AB  - A fluctuation-dissipation theorem, connecting all thermodynamic response
      functions to equilibrium fluctuations in the microcanonical ensemble, is derived
      from classical mechanics. This particular problem is not included in the usual
      linear response scheme, since the relevant perturbations cannot be stated as
      additional terms in the Hamiltonian. In experiments where the only control
      parameter is the heat flow, dissipation is present in terms of an entropy flow
      from the system to the surroundings. As an example, the full frequency-dependent
      thermodynamic response matrix is extracted from simulations of a supercooled
      binary Lennard-Jones fluid. This fluid shows rather high relaxation strength of
      all response functions, except of the adiabatic compressibility. The low
      frequency limit of all thermodynamic susceptibilities increases as temperature is
      decreased along an isocore.

PMID- 11969786
TI  - Cavitation induced by explosion in an ideal fluid model.
AB  - We discuss the problem of an explosion in the cubic-quintic superfluid model, in
      relation to some experimental observations. We show numerically that an explosion
      in such a model might induce a cavitation bubble for large enough energy. This
      gives a consistent view for rebound bubbles in superfluid and we identify the
      loss of energy between the successive rebounds as radiated waves. We compute self
      similar solution of the explosion for the early stage, when no bubbles have been
      nucleated. The solution also gives the wave number of the excitations emitted
      through the shock wave.

PMID- 11969787
TI  - Self-consistent turbulence in the two-dimensional nonlinear Schrodinger equation
      with a repulsive potential.
AB  - The dynamics of dark solitons (vortices) with the same topological charge
      (vorticity) in the two-dimensional nonlinear Schrodinger (NLS) equation in a
      defocusing medium is studied. The dynamics differ from those in incompressible
      media due to the possibility of energy and angular momentum radiation. The
      problem of the breakup of a multicharged dark soliton, which is a local decrease
      of the wave function intensity, into a number of chaotically moving vortices with
      single charge, is studied both analytically and numerically. After an initial
      period of intensive wave radiation, there emerges a nonuniform, steady turbulent
      self-organized motion of these vortices which is restricted in space by the size
      of the potential well of the initial multicharged dark soliton. Separate orbits
      of finite widths arise in this turbulent motion. That is, the statistical
      probability to observe a vortex in a given point has maxima near certain points
      (orbit positions). In spite of the fact that numerical calculations were
      performed in a finite region, the turbulent distributions of the vortices do not
      depend on the size of the container when its radius is larger than the size of
      the potential well of the primary multicharged dark soliton. The steady turbulent
      distribution of vortices on these orbits can be obtained as the extremal of the
      Lyapunov functional of the NLS equation, and obeys some simple rules. The first
      is the absence of Cherenkov resonance with linear (sound) waves. The second is
      the condition of a potential energy maximum in the region of vortex motion. These
      conditions give an approximately equidistant disposition of orbits of the same
      number of vortices on each orbit, which corresponds to a constant rotating
      velocity. The magnitude of this velocity is mainly determined by the sound
      velocity. An integral estimation of the self-consistent rotation of the vortex
      zone is given.

PMID- 11969788
TI  - Surface-induced ordering of a molecular fluid of flat hexagonal structure in a
      narrow graphite slit.
AB  - We systematically investigate by Monte Carlo simulations the role of the wall
      structure on a fluid of flat hexagonal molecules confined between two graphite
      walls. Our simulations show that the centers of mass of the molecules in
      different layers undergo an order-disorder transition as the wall separation
      increases, irrespective of the details of the wall structure. The wall structure
      thus becomes insignificant for the intervening fluid even down to a surprisingly
      low wall separation.

PMID- 11969789
TI  - Differential criterion of a bubble collapse in viscous liquids.
AB  - The present work is devoted to a model of bubble collapse in a Newtonian viscous
      liquid caused by an initial bubble wall motion. The obtained bubble dynamics
      described by an analytic solution significantly depends on the liquid and bubble
      parameters. The theory gives two types of bubble behavior: collapse and viscous
      damping. This results in a general collapse condition proposed as the sufficient
      differential criterion. The suggested criterion is discussed and successfully
      applied to the analysis of the void and gas bubble collapse.

PMID- 11969790
TI  - Transition to turbulence in a shear flow.
AB  - We analyze the properties of a 19-dimensional Galerkin approximation to a
      parallel shear flow. The laminar flow with a sinusoidal shape is stable for all
      Reynolds numbers Re. For sufficiently large Re additional stationary flows occur;
      they are all unstable. The lifetimes of finite amplitude perturbations shows a
      fractal dependence on amplitude and Reynolds number. These findings are in accord
      with observations on plane Couette flow and suggest a universality of this
      transition scenario in shear flows.

PMID- 11969791
TI  - Fingering instability in combustion: an extended view.
AB  - We detail the experimental situation concerning the fingering instability that
      occurs when a solid fuel is forced to burn against a horizontal oxidizing wind.
      The instability appears when the Rayleigh number for convection is below
      criticality. The focus is on the developed fingering state. We present direct
      measurements of the depletion of oxygen by the front as well as new results that
      connect heat losses to the characteristic scale of the instability. In addition,
      we detail the experimental system, elaborate (qualitatively and quantitatively)
      on the results that were previously presented, and discuss new observations. We
      also show that the same phenomenological model applies to electrochemical
      deposition.

PMID- 11969792
TI  - Electric-field-induced front deformation of Belousov-Zhabotinsky waves.
AB  - Experimental evidence is given of deformations in the vertical profiles of
      ferroin-catalyzed Belousov-Zhabotinsky waves propagating in thin horizontal
      cuvettes under an imposed dc electric field. While no deformations are seen in a
      zero field, for low negative field, or for any positive field, a pronounced S
      shaped deformation does occur when a wave is exposed to a negative field above
      some critical magnitude. The observed phenomena are discussed on the basis of the
      convective flows that are assumed to increase in the negative field resulting
      from changes in the longitudinal profile of the wave.

PMID- 11969794
TI  - Dynamic properties of Lennard-Jones fluids and liquid metals.
AB  - The dependence of the dynamic properties of liquid metals and Lennard-Jones
      fluids on the characteristics of the interaction potentials is analyzed.
      Molecular-dynamics simulations of liquids in analogous conditions but assuming
      that their particles interact either through a Lennard-Jones or a liquid-metal
      potential were carried out. The Lennard-Jones potentials were chosen so that both
      the effective size of the particles and the depth of the potential well were very
      close to those of the liquid-metal potentials. In order to investigate the extent
      to which the dynamic properties of liquids depend on the short-range attractive
      interactions as well as on the softness of the potential cores, molecular
      dynamics simulations of the same systems but assuming purely repulsive
      interactions with the same potential cores were also performed. The study
      includes both single-particle dynamic properties, such as the velocity
      autocorrelation functions, and collective dynamic properties, such as the
      intermediate scattering functions, the dynamic structure factors, the
      longitudinal and transverse current correlations, and the transport coefficients.

PMID- 11969793
TI  - Convection in the presence of a first-order phase change.
AB  - We report experimental and theoretical results for two-phase convection in a thin
      horizontal layer of a fluid with a first-order phase change and heated from
      below. A top layer of the nematic phase of a liquid crystal is located above the
      bottom layer of the isotropic phase of the same substance. A horizontal field of
      1000 G is applied in order to align the director of the nematic phase. Over some
      ranges of the thickness of the isotropic phase, and in sufficiently large thermal
      gradients, the more dense nematic phase can be stably stratified above the less
      dense isotropic one, with a stable interface between them. Based on the equations
      of motion derived for this problem by Busse and Schubert [J. Fluid Mech. 46, 801
      (1971)], we evaluate the bifurcation lines between the quiescent and convecting
      states and the corresponding critical wave vectors as a function of the interface
      position. We report experimental measurements based on Nusselt-number
      determinations for the locations of the bifurcation lines. They are in good
      agreement with the theoretical results. We also report approximate determinations
      of the critical wave numbers which are semiquantitatively consistent with the
      theory. A great diversity of patterns is observed in the convecting states,
      including normal and parallel rolls, rolls with defects and disorder, target
      patterns and spirals, and cellular flow with upflow or downflow at the cell
      center. These patterns are discussed in terms of the breaking of the mirror
      symmetry at the horizontal midplane by the interface, and in terms of the
      orienting effects of the magnetic field.

PMID- 11969795
TI  - Amplitude equation and pattern selection in Faraday waves.
AB  - A nonlinear theory of pattern selection in parametric surface waves (Faraday
      waves) is presented that is not restricted to small viscous dissipation. By using
      a multiple scale asymptotic expansion near threshold, a standing wave amplitude
      equation is derived from the governing equations. The amplitude equation is of
      gradient form, and the coefficients of the associated Lyapunov function are
      computed for regular patterns of various symmetries as a function of a viscous
      damping parameter gamma. For gamma approximately 1, the selected wave pattern
      comprises a single standing wave (stripe pattern). For gamma<<1, patterns of
      square symmetry are obtained in the capillary regime (large frequencies). At
      lower frequencies (the mixed gravity-capillary regime), a sequence of sixfold
      (hexagonal), eightfold, ...patterns are predicted. For even lower frequencies
      (gravity waves) a stripe pattern is again selected. Our predictions of the
      stability regions of the various patterns are in quantitative agreement with
      recent experiments conducted in large aspect ratio systems.

PMID- 11969796
TI  - Extended self-similarity and dissipation range dynamics of three-dimensional
      turbulence.
AB  - We carry out a self-consistent calculation of the structure functions in the
      dissipation range using the Navier-Stokes equation. Combining these results with
      the known structures in the inertial range, we actually propose crossover
      functions for the structure functions that take one smoothly from the inertial to
      the dissipation regime. These crossover functions are shown to exhibit extended
      self-similarity properties consistent with experimental findings.

PMID- 11969797
TI  - Quantum theory of chiral interactions in cholesteric liquid crystals.
AB  - The effective chiral interaction between molecules arising from long-range
      quantum interactions between fluctuating charge moments is analyzed in terms of a
      simple model of chiral molecules. This model is based on the approximations that
      (a) the dominant excited states of a molecule form a band whose width is small
      compared to the average energy of excitation above the ground state and (b)
      biaxial orientational correlation between adjacent molecules can be neglected.
      Previous treatments of quantum chiral interactions have been based on a multipole
      expansion of the effective interaction energy within second-order perturbation
      theory. We consider a system consisting of elongated molecules and, although we
      invoke the expansion in terms of coordinates transverse to the long axis of
      constituent molecules, we treat the longitudinal coordinate exactly. Such an
      approximation is plausible for molecules in real liquid crystals. The macroscopic
      cholesteric wave vector Q (Q=2 pi/P, where P is the pitch) is obtained via
      Q=h/K(2), where K2 is the Frank elastic constant for twist and h is the torque
      field which we calculate from the effective chiral interaction kappa(IJ)a(I)xa(J)
      x R(IJ), where the unit vector a(I) specifies the orientation of molecule I and
      R(IJ) is the displacement of molecule I relative to molecule J. We identify two
      distinct physical limits depending on whether one or both of the interacting
      molecules are excited in the virtual state. When both molecules are excited, we
      regain the R(-8)(IJ) dependence of kappa(IJ) on intermolecular separation found
      previously by Van der Meer et al. [J. Chem. Phys. 65, 3935 (1976)]. The two
      molecule, unlike the one-molecule term, can be interpreted in terms of a
      superposition of pairwise interactions between individual atoms (or local chiral
      centers) on the two molecules. Contributions to kappa(IJ) when one molecule is
      excited in the virtual state are of order R(-7)(IJ) for helical molecules which
      are assumed not to have a global dipole moment, but whose atoms possess a dipole
      moment. It is shown that for a helical molecule Q can have either the same or the
      opposite sign as the chiral pitch of an individual molecule, depending on the
      details of the anisotropy of the atomic polarizability. The one-molecule
      mechanism can become important when the local atomic dipoles become sizable,
      although biaxial correlations (ignored here) should then be taken into account.
      Our results suggest how the architecture of molecular dipole moments might be
      adjusted to significantly influence the macroscopic pitch.

PMID- 11969798
TI  - Smectic-A*-smectic-C* transition in a ferroelectric liquid crystal without
      smectic layer shrinkage.
AB  - The smectic layer spacing of a nonfluorinated ferroelectric liquid crystal (FLC)
      compound with almost no shrinkage and only minor tendency to form zigzag defects
      was characterized by small angle x-ray diffraction. The material lacks a nematic
      phase. The smectic-A*-smectic-C* phase transition was studied by measuring the
      thermal and electric field response of the optical tilt and the electric
      polarization. These properties are described very well by a Landau expansion even
      without introduction of a higher-order Theta(6) term. This result suggests a pure
      second-order phase transition far from tricriticality and differs considerably
      from the typical behavior of the A*-C* transition in most FLC materials.

PMID- 11969799
TI  - Dynamics of soft and semisoft nematic elastomers.
AB  - We analyze analytically and numerically the dynamics of how a nematic elastomer
      an anisotropic rubber-responds elastically and orientationally to an imposed
      strain. Because positional and orientational degrees of freedom are coupled, the
      response is not the simple exponential one might expect for a viscous system.
      Indeed, as a result of this nonlinear coupling, the different modes decay in two
      qualitatively different ways: with either two distinct or with the same
      exponential laws, depending, respectively, on whether there is or there is not
      complete reorientation of the molecular long axes. In addition, at the special
      values of the strain that form the boundaries between different equilibrium
      behaviors, relaxation is much slower, i.e., it follows a power law.

PMID- 11969800
TI  - Turbulence to turbulence transition in homeotropically aligned nematic liquid
      crystals.
AB  - In this paper, a study of the electrically driven turbulent-turbulent transition
      in a homeotropically oriented nematic sample is reported. The transition has the
      characteristics of a nucleation process, and its threshold has been
      experimentally determined. The nucleation rate and the growth velocity of the new
      turbulent nuclei are also reported.

PMID- 11969801
TI  - Biaxial modeling of the structure of the chevron interface in smectic liquid
      crystals.
AB  - We have included the inherent molecular biaxiality of the smectic C phase in a
      model of the chevron structure. This molecular biaxiality is related to a
      hindered rotation about the molecular long axis which for chiral, polar molecules
      induces a spontaneous polarization. Through the coupling between biaxiality and
      the smectic cone angle, continuity of the molecular distribution at the chevron
      interface leads to changes in the cone angle. Under certain approximations we are
      able to find analytic expressions for the chevron structure and consequently
      estimate the width of the chevron interface. There are in fact two correlation
      lengths which govern variations in the cone angle and the biaxiality.

PMID- 11969802
TI  - Experimental observation of multicritical behaviors in pressure-temperature
      diagrams of pure compounds with twist grain boundary phases.
AB  - In order to study critical behaviors of pure compounds anticipated by Renn and
      Lubensky's theoretical calculations, high-pressure experiments have been
      performed on six tolan series homologous to the 3-fluoro-4-[(R) or (S)
      methylheptyloxy]-4'-(4"-alkoxy-2",3"-difluorobenzoyloxy), which exhibit the twist
      grain boundary (TGB(A) and TGB(C)) mesophases. Measurements were carried out by
      thermobarometric analysis. Six pressure-temperature phase diagrams are
      determined. The studies establish the existence of multicritical points twisted
      smectic-C (S*(C))-TGB(C)-TGB(A), TGB(C)-TGB(A)-cholesteric nematic (N*) and S*(C)
      TGB(C)-N* for single component systems in pressure-temperature (P-T) phase
      diagrams. Our results also show that a pressure increase has the same effect on
      the (P-T) phase diagrams as a decreasing number of carbon atoms in the aliphatic
      chain; then pressure change can have the same effects on intermolecular
      interactions as those observed when shortening the molecular length. The
      existence of transition lines with negative slope values was also found. The
      experimental results are in qualitative agreement with the model proposed by Renn
      and Lubensky.

PMID- 11969803
TI  - Nematic ordering in a cell with modulated surface anchoring: effects of
      flexoelectricity.
AB  - We have analyzed molecular ordering in a nematic sample sandwiched between two
      parallel substrates, characterized by a periodically varying anchoring easy axis.
      If the periodicity lambda is smaller than the Debye screening length l(D) and the
      nematic material possesses flexoelectric properties, it is necessary to take into
      account also the electrostatic and flexoelectric contributions in the
      thermodynamical potential when the actual director field is determined. In this
      framework, for small deviations from the homeotropic alignment we have derived
      analytical expressions for the tilt angle (theta) and the electrical potential.
      To establish a connection with experimentally observable quantities, we have
      related the theta profile to the average <theta(2)> and investigated its behavior
      for different values of lambda, the flexoelectric coefficient, and the anchoring
      strength w. Our results indicate that in a nematic with pronounced flexoelectric
      properties for small enough lambda, a kind of subsurface deformation appears,
      which substantially decreases <theta(2)>. Therefore, effects of flexoelectricity
      cannot be neglected in treating nematic cells with modulated anchoring which
      allows bistable ordering.

PMID- 11969804
TI  - Nematic order in nanoscopic liquid crystal droplets.
AB  - We have used atomistic molecular-dynamics simulations to model the detailed
      molecular configuration of 5CB (4-n-pentyl-4'-cyanobiphenyl) molecules in the
      form of a nanoscopic liquid crystal droplet in a vacuum microgravity environment.
      We find the equilibrium state of droplets consisting of as few as 26 or 50
      molecules to exhibit significant nematic ordering. The shape of the droplets is
      also anisotropic, but there is little angular correlation between the nematic
      director and the long axis of the droplet. Some tendency to micelle formation is
      observed in droplets of 50 molecules.

PMID- 11969805
TI  - Nuclear magnetic relaxation without spin diffusion in polymers at interfaces.
AB  - We consider theoretically the possibility of solid state NMR experiments with
      frozen linear polymer chains at interfaces. Three different cases are studied,
      namely, when the macromolecules are grafted on the surface, when they are
      adsorbed, and when they are very strongly adsorbed from a melt that is
      subsequently washed by a good solvent. The latter case is somewhat intermediate
      between the two former ones. For each case, we consider the relaxation when
      paramagnetic centers are located on the surface. We show that the shape of the
      relaxation curves depends critically on the monomer concentration profile, and
      exhibits characteristic power-law variations.

PMID- 11969806
TI  - Granular cooling of hard needles.
AB  - We have developed a kinetic theory of hard needles undergoing binary collisions
      with loss of energy due to normal and tangential restitution. In addition, we
      have simulated many particle systems of granular hard needles. The theory, based
      on the assumption of a homogeneous cooling state, predicts that granular cooling
      of the needles proceeds in two stages: An exponential decay of the initial
      configuration to a state where translational and rotational energies take on a
      time independent ratio (different from unity), followed by an algebraic decay of
      the total kinetic energy of approximately t(-2). The simulations support the
      theory very well for low and moderate densities. For higher densities, we have
      observed the onset of the formation of clusters and shear bands.

PMID- 11969807
TI  - Structural rearrangement of solid surfaces due to competing adsorbate-substrate
      interactions.
AB  - Employing a generalized lattice gas theory and the Brownian dynamics simulation,
      we show that the competing displacive interaction in an adsorbate may cause a
      continuous distortive transition in the underlying substrate. The threshold for
      the transition is determined by the competition of the substrate rigidity and the
      quasielastic energy induced by the adsorbate. In the presence of a strong pinning
      and repulsive lateral interaction, the resulting structure appears as a
      compromise between the square lattice of the substrate and the hexagonal
      arrangement of the adsorbate. For hexagonal substrate lattices the simulation
      demonstrates that various adsorbate structures (from honeycomb lattices to
      quasicrystalline pentagonal configurations) may be observed, depending on the
      effective radii of interaction. Due to the long-ranged coupling the substrate may
      acquire a substructure induced by the adsorbate. This paper represents a
      generalization of the work published in Phys. Rev. Lett. 81, 3904 (1998).

PMID- 11969808
TI  - Statistics of shock waves in a two-dimensional granular flow.
AB  - We have investigated the dynamics of shock waves in a single layer of uniform
      balls in a small-angle two-dimensional funnel. When the funnel half-angle 0
      degrees < or approximately beta < or approximately 2 degrees, the flow is
      intermittent and kinematic shock waves are observed to propagate against the
      flow. We have used fast video equipment and image analysis methods to study the
      statistics of the shock waves. It is found that their speed and frequency
      increase with the distance from the outlet. In particular, the shock speed scales
      as the ratio of the local funnel width to the width of the funnel outlet. Various
      kinds of interactions between shock waves are observed, including repulsion. New
      shock waves are only created at those sites where a close-packed triangular
      packing of the monodisperse balls fits across the funnel.

PMID- 11969809
TI  - Stress propagation through frictionless granular material.
AB  - We examine the network of forces to be expected in a static assembly of hard,
      frictionless spherical beads of random sizes, such as a colloidal glass. Such an
      assembly is minimally connected: the ratio of constraint equations to contact
      forces approaches unity for a large assembly. However, the bead positions in a
      finite subregion of the assembly are underdetermined. Thus to maintain
      equilibrium, half of the exterior contact forces are determined by the other
      half. We argue that the transmission of force may be regarded as unidirectional,
      in contrast to the transmission of force in an elastic material. Specializing to
      sequentially deposited beads, we show that forces on a given buried bead can be
      uniquely specified in terms of forces involving more recently added beads. We
      derive equations for the transmission of stress averaged over scales much larger
      than a single bead. This derivation requires the ansatz that statistical
      fluctuations of the forces are independent of fluctuations of the contact
      geometry. Under this ansatz, the d(d+1)/2-component stress field can be expressed
      in terms of a d-component vector field. The procedure may be generalized to
      nonsequential packings. In two dimensions, the stress propagates according to a
      wave equation, as postulated in recent work elsewhere. We demonstrate similar
      wave-like propagation in higher dimensions, assuming that the packing geometry
      has uniaxial symmetry. In macroscopic granular materials we argue that our
      approach may be useful even though grains have friction and are not packed
      sequentially.

PMID- 11969810
TI  - Kramers potential study of the Rouse-like dynamics of short alkane chains.
AB  - In this work we present a Kramers potential study of the orientational dynamics
      and shear viscosity of short chain alkanes. In this approach the determination of
      the orientational relaxation time is reduced to the calculation of static moments
      of single chain conformations. We study a chemically realistic alkane model that
      asymptotically produces Gaussian chain conformations by means of a Monte Carlo
      simulation. Our results are applicable to single chain descriptions of polymer
      melt dynamics and to the intrinsic viscosity of molecules in a Theta solvent.
      When we map the unknown time unit of our relaxation time result for one
      particular chain length and temperature to the value obtained for the same
      parameters from a molecular dynamics simulation of a melt of these chains, we are
      able to reproduce the experimental data on the chain length dependence of the
      melt viscosity of alkane chains at this temperature.

PMID- 11969811
TI  - Thermodynamic basis for a variational model for crystal growth.
AB  - Variational models provide an alternative approach to standard sharp interface
      models for calculating the motion of phase boundaries during solidification. We
      present a correspondence between objective functions used in variational
      simulations and specific thermodynamic functions. We demonstrate that variational
      models with the proposed identification of variables are consistent with
      nonequilibrium thermodynamics. Variational models are derived for solidification
      of a pure material and then generalized to obtain a model for solidification of a
      binary alloy. Conservation laws for internal energy and chemical species and the
      law of local entropy production are expressed in integral form and used to
      develop variational principles in which a "free energy," which includes an
      interfacial contribution, is shown to be a decreasing function of time. This free
      energy takes on its minimum value over any short time interval, subject to the
      laws of conservation of internal energy and chemical species. A variational
      simulation based on this model is described, and shown for small time intervals
      to provide the Gibbs-Thomson boundary condition at the solid-liquid interface.

PMID- 11969812
TI  - Instability of the Kolmogorov flow in a soap film.
AB  - We examine the instability of a soap film flow driven by a time-independent force
      that is spatially periodic in the direction perpendicular to the forcing
      (Kolmogorov flow). Linear stability analysis of an idealized model of this flow
      predicts a critical Reynolds number R(c) is approximately equal to the square
      root of 2. In our soap film experiment, we find a critical value R(c) is
      approximately equal to 70. This discrepancy can be ascribed to frictional effects
      from viscous coupling of gas to the film, which is neglected in the idealized
      model. The kinematic viscosity of the surrounding gas and the thickness of gas
      layers on each side of the soap film are varied in the experiments to better
      understand these frictional effects. Our observations indicate that flow in the
      soap film cannot be decoupled from flow in the surrounding gas.

PMID- 11969813
TI  - Irreversible adsorption of diffusing hard disks: an effective medium approach.
AB  - We propose an effective medium theory to analyze the kinetics of nonsequential
      adsorption of colloidal particles, including transport and blocking effects,
      valid at all values of surface coverage. The theory is applied to the
      irreversible adsorption of diffusing hard disks obtaining a kinetic law, which is
      in excellent agreement with nonsequential computer simulations at all densities
      of adsorbed particles.

PMID- 11969814
TI  - Nonlinear dynamics of Aeolian sand ripples.
AB  - We study the initial instability of flat sand surface and further nonlinear
      dynamics of wind ripples. The proposed continuous model of ripple formation
      allowed us to simulate the development of a typical asymmetric ripple shape and
      the evolution of a sand ripple pattern. We suggest that this evolution occurs via
      ripple merger preceded by several soliton-like interaction of ripples.

PMID- 11969815
TI  - Elasticity effects on domain coarsening of the lamellar-gyroid transition
      observed in a nonionic surfactant system.
AB  - The coarsening process of the gyroid phase of a nonionic surfactant system is
      investigated by time resolved small angle neutron scattering (SANS) and small
      angle neutron Laue diffraction techniques. The time evolution of SANS patterns
      shows anomalous coarsening of the gyroid domains. The observed Laue spot from a
      gyroid domain becomes elongated along the radial direction with the elapse of
      time and at a certain time the elongated spot is split into two spots. The
      results can be interpreted as follows. During the coarsening process, mismatch of
      the lattice orientation at the domain boundary brings strong stress to the gyroid
      domain, resulting in the distortion of the domain. The stored stress in the
      domain finally brings splitting of the gyroid domain. The elastic and fragile
      nature of the gyroid domains composed of the "soft matter" is responsible for the
      anomalous coarsening.

PMID- 11969816
TI  - Neutron scattering and molecular correlations in a supercooled liquid.
AB  - We show that the intermediate scattering function S(n)(q,t) for neutron
      scattering (ns) can be expanded naturally with respect to a set of molecular
      correlation functions that give a complete description of the translational and
      orientational two-point correlations in the liquid. The general properties of
      this expansion are discussed with special focus on the q dependence, and hints
      for a (partial) determination of the molecular correlation functions from neutron
      scattering results are given. The resulting representation of the static
      structure factor S(n)(q) is studied in detail for a model system using data from
      a molecular dynamics simulation of a supercooled liquid of rigid diatomic
      molecules. The comparison between the exact result for S(n)(q) and different
      approximations that result from a truncation of the series representation
      demonstrates its good convergence for the given model system. On the other hand
      it shows explicitly that the coupling between translational and orientational
      degrees of freedom of each molecule and rotational motion of different molecules
      cannot be neglected in the supercooled regime. Further we report the existence of
      a prepeak in the ns static structure factor of the examined fragile glass former,
      demonstrating that prepeaks can occur even in the most simple molecular liquids.
      Besides examining the dependence of the prepeak on the scattering length and the
      temperature we use the expansion of S(n)(q) into molecular correlation functions
      to point out the intermediate range orientational order as its principle origin.

PMID- 11969817
TI  - Dynamics of spherical particles on a surface: collision-induced sliding and other
      effects.
AB  - We present a model for the motion of hard spherical particles on a two
      dimensional surface. The model includes both the interaction between the
      particles via collisions and the interaction of the particles with the substrate.
      We analyze in detail the effects of sliding and rolling friction, which are
      usually overlooked. It is found that the properties of this particulate system
      are influenced significantly by the substrate-particle interactions. In
      particular, sliding of the particles relative to the substrate after a collision
      leads to considerable energy loss for common experimental conditions. The
      presented results provide a basis that can be used to realistically model the
      dynamical properties of the system, and provide further insight into density
      fluctuations and related phenomena of clustering and structure formation.

PMID- 11969819
TI  - Frequency-dependent shear viscosity, sound velocity, and sound attenuation near
      the critical point in liquids. III. The shear viscosity.
AB  - We compare theoretical results for the shear viscosity calculated in one-loop
      order within the field-theoretical method of the renormalization-group theory
      with experiments. Our expressions describe the nonasymptotic crossover in both
      temperature and density, and allow us to consider effects of finite gravitation
      and finite frequency at which the experiments are performed. In doing so we treat
      the critical exponent x(eta) of the shear viscosity as an independent parameter,
      keeping the one-loop value of the Kawasaki amplitude fixed. Within our model we
      also consider the temperature and density dependence of the thermal diffusion
      including gravitational effects.

PMID- 11969818
TI  - Extended (n/v)-Stillinger cluster for use in the theory of homogeneous
      nucleation.
AB  - In this paper we develop a theory for an extended version of the (n/v)-Stillinger
      cluster that has been used in nucleation theory, where n means the number of
      particles constituting the cluster characterized by the volume v. The "extended
      cluster" incorporates some of the surrounding supersaturated vapor. This cluster,
      although requiring more extensive simulation than the original (n/v)-Stillinger
      cluster, is almost devoid of approximation. It maintains the non-ad-hoc nature of
      the original (n/v)-Stillinger cluster implicitly. The theory of the cluster is
      also applicable to clusters which avoid redundancy by some other means than the
      so-called "connectivity requirement." Simulation of the extended cluster is now
      being implemented and will be used in the theory of the homogeneous nucleation
      rate.

PMID- 11969820
TI  - Percolation phenomenon of calcium bis(2-ethylhexyl) sulfosuccinate water-in-oil
      microemulsions by conductivity and dielectric spectroscopy measurements.
AB  - The sodium counterion (Na+) of the sodium bis(2-ethylhexyl) sulfosuccinate (AOT)
      surfactant was exchanged with calcium Ca2+ to investigate the counterion charge
      effect on the structure of water in normal decane microemulsions. Ohmic
      conductivity and dielectric permittivity measurements were performed on samples
      at constant water to surfactant mole ratio [water]/[Ca(AOT)(2)]=26.6. Increasing
      the volume fraction of the dispersed phase phi, a percolation phenomenon was
      observed at the constant temperature of 25 degrees C. The percolation threshold
      was found at phi approximately 15% by Ohmic conductivity and static dielectric
      permittivity studied as a function of phi, and by the frequency dependence of the
      complex permittivity. Critical exponents typical of the static percolation
      mechanism (formation of bicontinuous microemulsions) were found below and above
      threshold. The comparison of these results obtained for the two different
      counterions, Ca2+ and Na+, in AOT surfactant water in normal decane
      microemulsions allows detection of an important difference. The percolation below
      threshold is dynamic for the sodium-based microemulsions, accounting for the
      formation of clusters of droplets, whereas calcium-based microemulsions show a
      static percolation. For this system, the coalescence of droplets begins to occur
      below threshold at phi approximately 12%.

PMID- 11969821
TI  - Confidence in prediction by neural networks.
AB  - The idea that a trained network can assign a confidence number to its prediction,
      indicating the level of its reliability, is addressed and exemplified by an
      analytical examination of a perceptron with discrete and continuous output units.
      Results are derived for both Gibbs and Bayes scenarios. The information gain by
      the confidence number is estimated by various entropy measurements.

PMID- 11969822
TI  - Counterion-mediated, non-pairwise-additive attractions in bundles of like-charged
      rods.
AB  - Stiff polyelectrolyte chains, such as DNA, can attract each other in solution
      even though they have the same sign of charge. The attractions are mediated by
      multivalent counterions, which lead to an effective interaction at the two-chain
      level that is attractive at short range and repulsive at long range. However, the
      effective interchain interactions are not pairwise additive. We present a
      formulation that allows theoretical treatment of the many-chain problem without
      assuming pairwise additivity. We show that a bundle of chains held together by
      counterion-mediated attractions can be described in terms of a bulk and surface
      free energy, and discuss the temperature dependence of the attraction.

PMID- 11969823
TI  - Translational diffusion of flexible lipid chains in a Langmuir monolayer: a
      dynamic Monte Carlo study.
AB  - We report a computer simulation study of the lateral diffusion of
      conformationally disordered lipid molecules in a monolayer structure. The
      simulations were carried out with dynamic Monte Carlo methods, employing two
      different representations of the internal motions of the lipid chains. The
      classical Cohen-Turnbull theory is found to provide a good description of the
      simulated lateral diffusion coefficients at moderate densities. The substantial
      deviations found at low densities are attributed to the small density
      fluctuations needed to create the free volume required for the lateral diffusion
      process.

PMID- 11969824
TI  - Kinetic properties of multiquanta Davydov-like solitons in molecular chains.
AB  - The Fokker-Planck equation for multivibron solitons interacting with lattice
      vibrations in a molecular chain has been derived by means of the nonequilibrium
      statistical operator method. It was shown that a soliton undergoes diffusive
      motion characterized by two substantially different diffusion coefficients. The
      first one corresponds to the ordinary (Einsteinian or dissipative) diffusion and
      characterizes the soliton Brownian motion, while the second one corresponds to
      the anomalous diffusion connected with frictionless displacement of the soliton
      center of mass coordinate due to the interaction with phonons. Both processes are
      the consequence of the Cherenkov-like radiation of phonon quanta arising when
      soliton velocity approaches the phase speed of sound.

PMID- 11969825
TI  - Parameter dependence of stochastic resonance in the stochastic Hodgkin-Huxley
      neuron.
AB  - Recently, the phenomena of stochastic resonance (SR) have attracted much
      attention in the studies of the excitable systems under inherent noise, in
      particular, nervous systems. We study SR in a stochastic Hodgkin-Huxley neuron
      under Ornstein-Uhlenbeck noise and periodic stimulus, focusing on the dependence
      of properties of SR on stimulus parameters. We find that the dependence of the
      critical forcing amplitude on the frequency of the periodic stimulus shows a bell
      shaped structure with a minimum at the stimulus frequency, which is quite
      different from the monotonous dependence observed in the bistable system at a
      small frequency range. The frequency dependence of the critical forcing amplitude
      is explained in connection with the firing onset bifurcation curve of the Hodgkin
      Huxley neuron in the deterministic situation. The optimal noise intensity for
      maximal amplification is also found to show a similar structure.

PMID- 11969826
TI  - Test for low-dimensional determinism in electroencephalograms.
AB  - We tested low-dimensional determinism in an electroencephalogram (EEG), based on
      the fact that smoothness (continuity) on an embedded phase space is enough to
      imply determinism within time series. A modified version of the method developed
      by Salvino and Cawley [Phys. Rev. Lett. 73, 1091 (1994)] was used. In our method,
      we chose a box randomly and then estimated the mean directional element in the
      box containing the d+1 data points, where d is the embedding dimension. The
      global average for the mean local directional elements over the boxes, W, is a
      measure for smoothness. The nonlinear noise reduction method developed by Sauer
      [Physica D 58, 193 (1992)] is then applied to the EEG. We also compared the
      results for the EEG with those for its surrogate data. We found that the W values
      for the noise-reduced EEG had stable values around 0.35, which means that the EEG
      is not a low-dimensional deterministic signal. However, this method may not be
      applicable to the time series generated from high-dimensional deterministic
      systems. We cannot exclude the possibility that the determinism in the EEG may be
      too high-dimensional to be detected with current methods.

PMID- 11969827
TI  - Model for spatial microtubule oscillations.
AB  - Under particular in vitro conditions, oscillating spatial and temporal waves of
      assembled microtubules can be observed. A reaction-diffusion model is presented
      to reproduce these results. This model is based on a set of chemical reaction
      equations and extended to include spatial dependence and diffusion. The basic
      properties of the model are presented and the results are demonstrated to connect
      the observable waves with turbidimetric measurements. The results of the model
      are consistent with experimental findings.

PMID- 11969828
TI  - Mass extinction in a dynamical system of evolution with variable dimension.
AB  - Introducing the effect of extinction into the so-called replicator equations in
      mathematical biology, we construct a general model where the diversity of
      species, i.e., the dimension of the equation, is a time-dependent variable. The
      system shows very different behavior from the original replicator equation, and
      leads to mass extinction when the system initially has high diversity. The
      present theory can serve as a mathematical foundation for the paleontologic
      theory for mass extinction. This extinction dynamics is a prototype of dynamical
      systems where the variable dimension is inevitable.

PMID- 11969829
TI  - Depletion interaction of casein micelles and an exocellular polysaccharide.
AB  - Casein micelles become mutually attractive when an exocellular polysaccharide
      produced by Lactococcus lactis subsp. cremoris NIZO B40 (hereafter called EPS) is
      added to skim milk. The attraction can be explained as a depletion interaction
      between the casein micelles induced by the nonadsorbing EPS. We used three
      scattering techniques (small-angle neutron scattering, turbidity measurements,
      and dynamic light scattering) to measure the attraction. In order to connect the
      theory of depletion interaction with experiment, we calculated structure factors
      of hard spheres interacting by a depletion pair potential. Theoretical
      predictions and all the experiments showed that casein micelles became more
      attractive upon increasing the EPS concentration.

PMID- 11969830
TI  - Synchronization in the human cardiorespiratory system.
AB  - We investigate synchronization between cardiovascular and respiratory systems in
      healthy humans under free-running conditions. For this aim we analyze
      nonstationary irregular bivariate data, namely, electrocardiograms and
      measurements of respiratory flow. We briefly discuss a statistical approach to
      synchronization in noisy and chaotic systems and illustrate it with numerical
      examples; effects of phase and frequency locking are considered. Next, we present
      and discuss methods suitable for the detection of hidden synchronous epochs from
      such data. The analysis of the experimental records reveals synchronous regimes
      of different orders n:m and transitions between them; the physiological
      significance of this finding is discussed.

PMID- 11969831
TI  - Energetic stabilization of d-camphor via weak neutral currents.
AB  - It is shown via a series of numerical tests on the camphor molecule, C10H16O,
      that the naturally occurring d-enantiomer is energetically stabilized with
      respect to its mirror image by electroweak force. The calculated energy
      difference between enantiomers, about 1.5 x 10(-19) hartree, is roughly eight
      orders of magnitude smaller than the upper bound suggested by available
      spectroscopic investigations on the frequency of a spectroscopic transition.
      However, such a difference is about ten times larger than previous estimates of
      parity-violating energy contributions reported in the literature for other chiral
      molecules, which makes the idea of electroweak stabilization of one enantiomer
      more reliable than expected before.

PMID- 11969832
TI  - Self-consistent axial modeling of surface-wave-produced discharges at low and
      intermediate pressures.
AB  - A model for description of the axial structure of a surface-wave-produced and 
      sustained plasma based on numerical calculation of a complete set of
      electrodynamic and kinetic equations is presented. The model includes a self
      consistent solution to the electron Boltzmann equation, a set of particle balance
      equations for electrons, excited atoms, atomic and molecular ions, as well as
      Maxwell's equations with appropriate boundary conditions. A gas thermal balance
      equation is used to predict the neutral gas temperature self-consistently.
      Precise calculations of discharge characteristics of an argon plasma column
      sustained by an azimuthally symmetric surface wave at low and intermediate gas
      pressures have been performed. A comparison with available experimental data is
      done in order to test the validity of the model.

PMID- 11969833
TI  - Modeling of particulate coagulation in low pressure plasmas.
AB  - In this paper we study the growth of nanometer particles in low pressure plasmas
      due to coagulation. We describe results of a model which involves the self
      consistent determination of plasma properties, the description of particle
      charging, as well as the description of the particle size distribution via
      solution of the general dynamic equation for an aerosol. Our results show that
      particle coagulation in the low pressure plasma is enhanced compared to
      coagulation in neutral aerosols due to the attraction of oppositely charged
      particles. The temporal behavior of the coagulation follows the same laws as
      coagulation of neutral particles as long as the density of nanometer particles is
      larger than the positive ion density in the plasma. The positive ion density can
      be considered as the critical density for coagulation to occur. We also show that
      the details of the particle charging mechanism are only of minor importance for
      the coagulation dynamics but of great importance for the accurate prediction of
      plasma parameters.

PMID- 11969834
TI  - Magnetic flux generation and wave emissions during coalescence of magnetic
      islands in pair plasmas.
AB  - It is shown by using a two-dimensional fully relativistic electromagnetic
      particle-in-cell code that the tearing instability in a current sheet of pair
      plasmas is caused by Landau resonances of both electrons and positrons. Strong
      magnetic flux can be generated during coalescence of magnetic islands in the
      nonlinear phase of the tearing instability. The magnetic flux produced in an O
      type magnetic island is caused by the counterstreaming instability found by
      Kazimura et al. [Astrophys. J. Lett. 498, L183 (1998); J. Phys. Soc. Jpn. 67,
      1079 (1998)]. It is also shown that charge separation with a quadrupole-like
      structure is generated from the localized strong magnetic flux. During the decay
      of the quadrupole-like charge structure as well as the magnetic flux, there
      appear wave emissions with high-frequency electromagnetic waves and Alfven waves
      as well as Langmuir waves.

PMID- 11969835
TI  - Beam-plasma coupling effects on the stopping power of dense plasmas.
AB  - The stopping power for ion beams in dense plasmas is investigated on the basis of
      quantum kinetic equations. Strong correlations between the beam ions and the
      plasma particles which occur for high ion charge numbers and strongly coupled
      plasmas are treated on the level of the statically screened T-matrix (binary
      collision) approximation. Dynamic screening effects are included using a combined
      scheme which considers both close collisions and collective effects. Applying
      this approach, the ion charge number dependence of the stopping power is
      determined. The result is a modification of the Z(2)(b) scaling law. In
      particular, the stopping power is reduced for strong beam-plasma coupling. Good
      agreement is found between T-matrix results and simulation data (particle-in-cell
      and molecular dynamics) for low beam velocities.

PMID- 11969836
TI  - Soft-x-ray laser interferometry of a pinch discharge using a tabletop laser.
AB  - We have used a tabletop soft-x-ray laser and a wave-front division interferometer
      to probe the plasma of a pinch discharge. A very compact capillary discharge
      pumped Ne-like Ar laser emitting at 46.9 nm was combined with a wave division
      interferometer based on Lloyd's mirror and Sc-Si multilayer-coated optics to map
      the electron density in the cathode region of the discharge. This demonstration
      of the use of tabletop soft-x-ray laser in plasma interferometry could lead to
      the widespread use of these lasers in the diagnostics of dense plasmas.

PMID- 11969837
TI  - Multiple scattering from gyrotropic bianisotropic cylinders of arbitrary cross
      sections using the modeling technique.
AB  - Based on the principle of the equivolumetric model, the multiple scattering from
      two-dimensional composite gyrotropic bianisotropic cylinders (GBC's) possessing a
      certain magnetic group of symmetry is studied by using the indirect modeling
      technique. At first, a mathematical formulation for the problem is carried out
      and its solution expressed in terms of a system of simultaneous linear equations
      of infinite order. The normal incident wave can be either TE(z) or TM(z)
      polarization. The linear equation system is then numerically solved by truncating
      the infinite series. Its numerical results are obtained and presented to
      characterize the co- and cross-polarized scattering by some typical composite
      GBC's. Especially, the multiple interactions among all the modeling cylinders,
      i.e., the host and guest cylinders as well as the guest and guest cylinders, are
      examined. Some phenomena of the interactions are found and discussed.

PMID- 11969838
TI  - Vacuum electron acceleration by coherent dipole radiation.
AB  - The validity of the concept of laser-driven vacuum acceleration has been
      questioned, based on an extrapolation of the well-known Lawson-Woodward theorem,
      which stipulates that plane electromagnetic waves cannot accelerate charged
      particles in vacuum. To formally demonstrate that electrons can indeed be
      accelerated in vacuum by focusing or diffracting electromagnetic waves, the
      interaction between a point charge and coherent dipole radiation is studied in
      detail. The corresponding four-potential exactly satisfies both Maxwell's
      equations and the Lorentz gauge condition everywhere, and is analytically
      tractable. It is found that in the far-field region, where the field distribution
      closely approximates that of a plane wave, we recover the Lawson-Woodward result,
      while net acceleration is obtained in the near-field region. The scaling of the
      energy gain with wave-front curvature and wave amplitude is studied
      systematically.

PMID- 11969839
TI  - Theory and design of a free-electron maser with two-dimensional feedback driven
      by a sheet electron beam.
AB  - The use of two-dimensional Bragg resonators of planar geometry, realizing two
      dimensional (2D) distributed feedback, is considered as a method of producing
      spatially coherent radiation from a large sheet electron beam. The spectrum of
      eigenmodes is found for a 2D Bragg resonator when the sides of the resonator are
      open and also when they are closed. The higher selectivity of the open resonator
      in comparison with the closed one is shown. A time-domain analysis of the
      excitation of an open 2D Bragg resonator by a sheet electron beam demonstrates
      that a single-mode steady-state oscillation regime may be obtained for a sheet
      electron beam of width 100-1000 wavelengths. Nevertheless, for a free-electron
      maser (FEM) with a closed 2D Bragg resonator, a steady-state regime can also be
      realized if the beam width does not exceed 50-100 wavelengths. The parameters for
      a FEM with a 2D planar Bragg resonator driven by a sheet electron beam based on
      the U-2 accelerator (INP RAS, Novosibirsk) are estimated and the project is
      described.

PMID- 11969840
TI  - Continuously tunable, high-power, single-mode radiation from a short-pulse free
      electron laser.
AB  - This paper gives the first demonstration of high-power, continuously tunable,
      narrowband radiation that is produced by means of a free-electron laser (FEL) in
      the far-infrared region of the electromagnetic spectrum. A Fox-Smith intracavity
      etalon was used to induce phase coherence between the 40 optical micropulses that
      were circulating in the laser cavity. The corresponding phase-locked spectrum
      consisted of a comb of discrete frequencies separated by 1 GHz. A pair of
      external Fabry-Perot etalons was used to filter out a single line from this
      spectrum. The power in the selected narrow line at 69 microm wavelength was equal
      to 250 mW during the macropulse of the laser. The spectral width of the selected
      line is as small as that of a single cavity mode, i.e., a fraction of 25 MHz, in
      single macropulses of the laser. The average bandwidth of 25 MHz is determined by
      mode hopping of the phase-locked FEL. The selected frequency hops over 25 MHz
      between the extrema of this band. The influence of partially coherent spontaneous
      emission and mode hopping on the final linewidth was studied. The narrow
      linewidth radiation was scanned in frequency over 1 GHz. We show that the
      possibilities to scan over smaller or larger frequency intervals are unlimited.

PMID- 11969841
TI  - Synchrotron radiation of crystallized beams.
AB  - We study the modifications of synchrotron radiation of charges in a storage ring
      as they are cooled. The pair correlation lengths between the charges are manifest
      in the synchrotron radiation and coherence effects exist for wavelengths longer
      than the coherence lengths between the charges. Therefore, the synchrotron
      radiation can be used as a diagnostic tool to determine the state (gas, liquid,
      crystal) of the charged plasma in the storage ring. We show also that the total
      power of the synchrotron radiation is significantly reduced for crystallized
      beams, both coasting and bunched. This opens the possibility of accelerating
      particles to ultrarelativistic energies using small-sized cyclic accelerators.

PMID- 11969842
TI  - Xuv resonant transition radiations from periodic stratified media.
AB  - General formulation of the xuv intensity emitted when relativistic electrons
      cross through any periodic stratified medium is presented in the framework of
      electromagnetism in continuous media. Application is made to the resonant
      transition radiation emitted in the geometries of both normal and oblique
      incidence. In the first case, agreement is found between our calculated results
      and published values. Intensity emitted by a periodic multilayer stack used in
      the Bragg conditions is determined and the practical interest of a such a
      radiation source is discussed.

PMID- 11969843
TI  - Stability of solitary wave trains in Hamiltonian wave systems.
AB  - A class of Hamiltonian nonlinear wave equations possessing complex solitary waves
      with exponential decay is studied. It is shown that the interpulse interactions
      in a train of nearly identical solitary waves with large separations between the
      individual solitary waves are approximately described by a double Toda lattice
      system, with two variables at each lattice site. Under certain conditions, which
      are explicitly identified as Cauchy-Riemann equations, the two dynamical
      variables are real and imaginary parts of a single complex variable, leading to
      the complex Toda lattice equations, which is a discrete integrable dynamical
      system. This analysis generalizes to certain nonintegrable partial differential
      equations a recent result for the nonlinear Schrodinger equation, and is
      important for the study of nonlinear communications channels in optical fibers.
      An example, the cubic-quintic nonlinear Schrodinger equation, is worked out in
      detail to show that the theory can be carried through analytically. The theory is
      used to determine the stability of an infinite chain of nearly identical pulses
      separated by large time intervals. The entire theory is nonperturbative in the
      sense that the nonlinear wave equation need not be a weak perturbation of an
      integrable one.

PMID- 11969844
TI  - Scaling theory for homogenization of the Maxwell equations.
AB  - A scaling theory for homogenization of the Maxwell equations is developed upon
      the representation of any field as a sum of its dipole, quadrupole, and magnetic
      dipole moments. This representation is exact and is connected neither with
      multipole expansion nor with the Helmholtz theorem. A chain of hierarchical
      equations is derived to calculate the moments. It is shown that the resulting
      macroscopic fields are governed by the homogenized Maxwell equations. Generally,
      these fields differ from the mean values of microscopic fields.

PMID- 11969845
TI  - Generation of optical domain-wall structures from modulational instability in a
      bimodal fiber.
AB  - We study experimentally modulational instability in a normally dispersive bimodal
      fiber under modal group-velocity-matching conditions. In the strong pump
      depletion regime, higher order sideband harmonics detected in the output spectra
      as well as autocorrelation measurements reveal the formation of subpicosecond
      domain-wall structures. Across these temporal structures the electromagnetic
      field distribution switches abruptly between the two transverse modes of the
      fiber. These structures are reminiscent of the so-called domain-wall soliton. Our
      results constitute therefore an experimental indication of the existence of this
      fundamental soliton.

PMID- 11969846
TI  - Stationary dark localized modes: discrete nonlinear Schrodinger equations.
AB  - Various kinds of stationary dark localized modes in discrete nonlinear
      Schrodinger equations are considered. A criterion for the existence of such
      excitations is introduced and an estimation of a localization region is provided.
      The results are illustrated in examples of the deformable discrete nonlinear
      Schrodinger equation, of the model of Frenkel excitons in a chain of two-level
      atoms, and of the model of a one-dimensional Heisenberg ferromagnetic in the
      stationary phase approximation. The three models display essentially different
      properties. It is shown that at an arbitrary amplitude of the background it is
      impossible to reach strong localization of dark modes. In the meantime, in the
      model of Frenkel excitons, exact dark compacton solutions are found.

PMID- 11969848
TI  - Modulational instability of bright solitary waves in incoherently coupled
      nonlinear Schrodinger equations.
AB  - We present a detailed analysis of the modulational instability (MI) of ground
      state bright solitary solutions of two incoherently coupled nonlinear Schrodinger
      equations. Varying the relative strength of cross-phase and self-phase effects we
      show the existence and origin of four branches of MI of the two-wave solitary
      solutions. We give a physical interpretation of our results in terms of the group
      velocity-dispersion- (GVD-) induced polarization dynamics of spatial solitary
      waves. In particular, we show that in media with normal GVD spatial symmetry
      breaking changes to polarization symmetry breaking when the relative strength of
      the cross-phase modulation exceeds a certain threshold value. The analytical and
      numerical stability analyses are fully supported by an extensive series of
      numerical simulations of the full model.

PMID- 11969847
TI  - Multicomponent photorefractive cnoidal waves: stability, localization, and
      soliton asymptotics.
AB  - An algorithm of building up a different class of stable self-consistent
      multicomponent periodical solutions of the nonlinear Schrodinger equation-
      multicomponent cnoidal waves--has been formulated by the example of a nonlinear
      wave propagating through a photorefractive crystal with a drift nonlinear
      response. Exact analytical expressions, describing distribution of light field in
      the components, have been obtained for solutions, which include up to three
      mutually incoherent components. It has been shown that such cnoidal waves are
      stable and their spatial structure is robust to collisions with the same cnoidal
      waves and to stochastic perturbations of the components' intensity distributions
      in a sufficiently wide range of changing spatial period.

PMID- 11969849
TI  - Femtosecond measurements of the time of flight of photons in a three-dimensional
      photonic crystal.
AB  - We report on experimental measurements of the propagation behavior of short
      optical pulses in a three-dimensional photonic crystal in the visible spectrum.
      The propagation delay of 70 fs light pulses transmitted through a sample of a fcc
      synthetic opal at frequencies lying in a photonic stop band was measured directly
      using a time-of-flight technique. Taking into account spectral reshaping of the
      transmitted pulses as well as the residual frequency chirp of the incoming
      pulses, it is found that the pulses significantly slow down at the photonic band
      edges.

PMID- 11969850
TI  - Wigner rotations and Iwasawa decompositions in polarization optics.
AB  - Wigner rotations and Iwasawa decompositions are manifestations of the internal
      space-time symmetries of massive and massless particles, respectively. It is
      shown to be possible to produce combinations of optical filters which exhibit
      transformations corresponding to Wigner rotations and Iwasawa decompositions.
      This is possible because the combined effects of rotation, phase-shift, and
      attenuation filters lead to transformation matrices of the six-parameter Lorentz
      group applicable to Jones vectors and Stokes parameters for polarized light
      waves. The symmetry transformations in special relativity lead to a set of
      experiments which can be performed in optics laboratories.

PMID- 11969851
TI  - Modulational instability of electromagnetic waves in birefringent fibers with
      periodic and random dispersion.
AB  - Modulational instability (MI) of electromagnetic waves in a birefringent fiber
      with a periodic dispersion (two-step dispersion management scheme) is
      investigated. The properties of new sidebands are studied. The strong variation
      of dispersion leads to the decreasing of the main MI region and the suppression
      of additional resonance. In the random dispersion case the MI of all frequencies
      of modulation in the normal dispersion region is predicted. In the anomalous
      dispersion case the decreasing of the main MI peak is calculated and changes in
      the spectral bandwidth of MI gain are found. The analytical predictions are
      confirmed by the numerical simulations of the full coupled nonlinear Schrodinger
      equations with periodic coefficients.

PMID- 11969852
TI  - Electromagnetic shocks on the optical cycle of ultrashort pulses in triple
      resonance Lorentz dielectric media with subfemtosecond nonlinear electronic Debye
      relaxation.
AB  - The dynamical evolution of an intense ultrashort sub-10-fs two-cycle optical
      pulse is considered as it propagates through a transparent third-order dielectric
      medium characterized by three resonance lines and a finite sub-fs relaxation time
      of the electronic nonlinearity. Numerical integration of the full Maxwell's
      equations incorporating triple-resonance Lorentz linear dispersion and Debye
      nonlinear dispersion, for a linearly polarized electromagnetic pulse centered at
      lambda(0)=1.24 microm in the normal dispersion region near the zero dispersion
      wavelength, shows the formation of shocks occurring on the optical cycle due to
      the generation of optical harmonics. The finite relaxation time of the nonlinear
      electronic response (sub-fs time scale) (i) slows down the steepening rate of the
      optical cycle; (ii) does not limit the generation of strongly phase matched
      optical harmonics, and consequently the development of infinitely sharp edges on
      the optical cycle producing its breaking when linear dispersion is not included;
      (iii) reduces the production of phase matched harmonics and consequently the
      sharpening of the jumps when dispersion is present, compared to the case of an
      instantaneous nonlinear response; and (iv) reduces the harmonic spectrum
      spreading and modulation at later times on the appearance of self-steepening of
      the electric field envelope.

PMID- 11969853
TI  - Randomly amplified discrete Langevin systems.
AB  - A discrete stochastic process involving random amplification with additive noise
      is studied analytically. If the non-negative random amplification factor b is
      such that <b(beta)>=1, where beta is any positive noninteger, then the steady
      state probability density function for the process will have power law tails of
      the form p(x) approximately 1/x(beta+1). This is a generalization of recent
      results for 0<beta<2 obtained by Takayasu, Sato, and Takayasu [Phys. Rev. Lett.
      79, 966 (1997)]. It is shown that the power spectrum of the time series x becomes
      Lorentzian, even when 1<beta<2, i.e., in the case of divergent variance.

PMID- 11969854
TI  - Ion association in model ionic fluids.
AB  - Monte Carlo simulations are used to investigate the temperature and pressure
      (density) dependence of ion association in the restricted primitive model. It is
      shown that at temperatures below the critical temperature T(c) the vapor consists
      almost exclusively of strongly bound ion pairs at or near contact. Significant
      ion-pair dissociation begins at temperatures very near T(c). This raises the
      possibility that compositional fluctuations between strongly bound and free ions
      influence the critical behavior. We note qualitative similarities between the
      present results and the Kosterlitz-Thouless transition in the two-dimensional
      Coulomb gas.

PMID- 11969855
TI  - Scaling behavior in a proportional voting process.
AB  - We perform a statistical analysis on the proportional elections held in Brazil in
      October 1998. We show that the distribution of votes among candidates for the
      whole country follows a power law N(v) is proportional to v(-alpha), with
      alpha=1.00+/-0.02, extending over two orders of magnitude. The voting
      distributions for several states of the federation also display scale-invariant
      behavior with alpha approximately equal to 1. We argue that this particular
      voting system can be modeled as a typical multiplicative process in which the
      choice of the candidate is governed by a product of probabilities.

PMID- 11969856
TI  - Self-sustained oscillations and chaos in space charge limited currents.
AB  - In kinetic simulations of a flow of charged particles between two parallel plate
      electrodes, it is found that chaotic responses in space charge limited currents
      can be induced by a periodically varying applied voltage.

PMID- 11969857
TI  - Reconstructing bifurcation diagrams from noisy time series using nonlinear
      autoregressive models.
AB  - We introduce a formalism for the reconstruction of bifurcation diagrams from
      noisy time series. The method consists in finding a parametrized predictor
      function whose bifurcation structure is similar to that of the given system. The
      reconstruction algorithm is composed of two stages: model selection and
      bifurcation parameter identification. In the first stage, an appropriate model
      that best represents all the given time series is selected. A nonlinear
      autoregressive model with polynomial terms is employed in this study. The
      identification of the bifurcation parameters from among the many model parameters
      is done in the second stage. The algorithm works well even for a limited number
      of time series.

PMID- 11969858
TI  - Tension gradients and Marangoni flows in nematic interfaces.
AB  - This brief report (i) presents equations that govern the balance of tangential
      forces in interfaces between isotropic viscous fluids and nematic liquid
      crystals, and (ii) establishes the physical origin of nematic Marangoni flows. It
      is shown that surface gradients in the orientation dependent surface free energy
      gives rise to tangential nematic Marangoni forces. Tangential nematic Marangoni
      forces are caused by surface gradients of the nematic tensor order parameter, and
      the kinetic coefficient characterizing this interfacial phenomenon is
      proportional to nematic elastic storage. Expressions of the Marangoni forces
      using a classical constitutive equation for the surface free energy are given for
      general and uniaxial nematic ordering states. Nematic Marangoni flows or
      nematocapillarity augments the class of Marangoni flows present in
      electrocapillarity, diffusocapillarity, and thermocapillarity.

PMID- 11969859
TI  - Absence of simulation evidence for critical depletion in slit pores.
AB  - Recent Monte Carlo simulation studies of a Lennard-Jones fluid confined to a
      mesoscopic slit pore have reported evidence of "critical depletion" in the pore
      local number density near the liquid-vapor critical point. In this Brief Report
      we demonstrate that the observed depletion effect is in fact a simulation
      artifact arising from small systematic errors associated with the use of long
      range corrections for the potential truncation. Owing to the large near-critical
      compressibility, these errors lead to significant changes in the pore local
      number density. We suggest ways of avoiding similar problems in future studies of
      confined fluids.

PMID- 11969860
TI  - Structure of supercooled and glassy water under pressure.
AB  - We use molecular-dynamics simulations to study the effect of temperature and
      pressure on the local structure of liquid water in parallel with neutron
      scattering experiments. We find, in agreement with experimental results, that the
      simulated liquid structure at high pressure is nearly independent of temperature,
      and remarkably similar to the known structure of the high-density amorphous ice.
      Further, at low pressure, the liquid structure appears to approach the
      experimentally measured structure of low-density amorphous ice as temperature
      decreases. These results are consistent with the postulated continuity between
      the liquid and glassy phases of H2O.

PMID- 11969861
TI  - Multiscale analysis of blood pressure signals.
AB  - We describe the multiresolution wavelet analysis of blood pressure waves in
      vasovagal syncope-affected patients compared with those in healthy people, using
      Haar and Gaussian bases. A comparison between scale-dependent and scale
      independent measures discriminating the two classes of subjects is made. What
      emerges is a sort of equivalence between these two methodological approaches,
      that is, both methods reach the same statistical significance of separation
      between the two classes.

PMID- 11969862
TI  - Comment on "Corresponding states of periodic structures in nematic liquid
      crystals".
AB  - Palangana, Simoes, Evangelista, and Arroteia [Phys. Rev. E 56, 4282 (1997)]
      (PSEA) propose a general scaling model for periodic wall patterns in the magnetic
      twist Freedericksz transition of nematics, performing an elastic energy analysis.
      We demonstrate that this model is incorrect because it does not consider
      consistently the hydrodynamic wavelength selection of the observed structures,
      but is based on the assumption of inappropriate model functions instead. It is
      shown that experimental data actually contradict the proposed theory. The
      approach of PSEA is particularly not suited to determine elastic constant ratios
      of nematic liquid crystals.

PMID- 11969864
TI  - Comment on "Merging of the alpha and beta relaxations in polybutadiene: a neutron
      spin echo and dielectric study".
AB  - The evaluation method of dielectric data based on a Williams product ansatz [A.
      Arbe, D. Richter, J. Colmenero, and B. Farago, Phys. Rev. E 54, 3853 (1996)] is
      not suited to the crossover region of the dynamic glass transition. This method
      is insensitive to the shape, position, or even existence of at least one of the
      relaxation functions if, in the extrapolation from below to above the crossover
      region, the two processes cross or approach one another. Since a crossover region
      without any particular change in the relaxation mechanism of these processes can
      in fact be adjusted by this method, better dielectric data for polybutadiene in
      the gigahertz frequency region are needed to determine whether or not there are
      peculiarities in the dielectric function. It would be an odd assumption that the
      many particularities in the crossover region in other instances are not reflected
      in the dielectric response.

PMID- 11969866
TI  - Universal equivalence of mean first-passage time and Kramers rate.
AB  - We prove that for an arbitrary time-homogeneous stochastic process, Kramers's
      flux-over-population rate is identical to the inverse of the associated mean
      first-passage time. In this way the mean first-passage time problem can be
      treated without making use of the adjoint equation in conjunction with cumbersome
      boundary conditions.

PMID- 11969867
TI  - Dilute Bose gas revised.
AB  - The well-known results concerning a dilute Bose gas with the short-range
      repulsive interaction should be reconsidered due to a thermodynamic inconsistency
      of the method being basic to much of the present understanding of this subject.
      The aim of our paper is to propose another way of treating the dilute Bose gas
      with an arbitrary strong interaction. Using the reduced density matrix of the
      second order and a variational procedure, this way allows us to escape the
      inconsistency mentioned and operate with singular potentials of the Lennard-Jones
      type. The derived expansion of the condensate depletion in powers of the boson
      density n=N/V reproduces the familiar result, while the expansion for the mean
      energy per particle is of the form epsilon=2 pi planck(2)an/m[1+128/(15 square
      root of [pi]) square root of [na(3)](1-5b/8a)+...], where a is the scattering
      length and b> or =0 stands for one more characteristic length depending on the
      shape of the interaction potential (in particular, for the hard spheres a=b). All
      the consideration concerns the zero temperature.

PMID- 11969868
TI  - Plasma-insulator transition of spin-polarized hydrogen.
AB  - A mixed classical-quantum density functional theory is used to calculate pair
      correlations and the free energy of a spin-polarized hydrogen plasma. A
      transition to an atomic insulator phase is estimated to occur around r(s)=2.5 at
      T=10(4) K, and a pressure P is approximately equal to 0.5 Mbar. Spin polarization
      is imposed to prevent the formation of H2 molecules.

PMID- 11969869
TI  - Elastic effects in disordered nematic networks.
AB  - Elastic effects in a model of disordered nematic elastomers are numerically
      investigated in two dimensions. Networks crosslinked in the isotropic phase
      exhibit an unusual soft mechanical response against stretching. It arises from a
      gradual alignment of orientationally correlated regions that are elongated along
      the director. A sharp crossover to a macroscopically aligned state is obtained on
      further stretching. The effect of random internal stress is also discussed.

PMID- 11969870
TI  - Nonlinear effects in the electrophoresis of a spherical colloidal particle.
AB  - The reduced electrophoretic mobility-reduced zeta potential relationship for a
      charged macroparticle is shown to be nonuniversal and to be highly nonlinear. In
      agreement with experimental results, a mobility reversal due to the macroion's
      charge inversion and a nonlinear dependence of the mobility on salt concentration
      is obtained.

PMID- 11969871
TI  - Ergodicity-breaking transition and high-frequency response in a simple free
      energy landscape.
AB  - We present a simple dynamical model described by a Langevin equation in a
      piecewise parabolic free-energy landscape, modulated by a temperature-dependent
      overall curvature. The zero-curvature point marks a transition to a phase with
      broken ergodicity. The frequency-dependent response near this transition is
      reminiscent of observations near the glass transition.

PMID- 11969872
TI  - Theoretical model of adsorption in a templated porous material.
AB  - We introduce a theoretical description of adsorption in a templated porous
      material modeled as a quenched binary mixture configuration with one component
      removed. Using tools from equilibrium statistical mechanics, we analyze the
      diagrammatic structure of and derive an approximate formula for this
      nonequilibrium material's porosity and Henry regime selectivity. We find that
      templating significantly increases the porosity as well as the selectivity for
      the larger component of a mixture.

PMID- 11969873
TI  - Effect of ordering on spinodal decomposition of liquid-crystal/polymer mixtures.
AB  - Partially phase-separated liquid-crystal/polymer dispersions display highly
      fibrillar domain morphologies that are dramatically different from the typical
      structures found in isotropic mixtures. To explain this, we numerically explore
      the coupling between phase ordering and phase-separation kinetics in model two
      dimensional fluid mixtures phase separating into a nematic phase, rich in liquid
      crystal, coexisting with an isotropic phase, rich in polymer. We find that phase
      ordering can lead to fibrillar networks of the minority polymer-rich phase.

PMID- 11969874
TI  - Mean discharge frequency locking in the response of a noisy neuron model to
      subthreshold periodic stimulation.
AB  - Leaky integrate-and-fire neuron models display stochastic resonance-like behavior
      when stimulated by subthreshold periodic signal and noise. Previous works have
      shown that matching between the time scales of the noise induced discharges and
      the modulation period can account for this phenomenon at low modulation
      amplitudes, but not large subthreshold modulation amplitude. In order to examine
      the discharge patterns of the model in this regime, we introduce a method for the
      computation of the power spectral density of the discharge train. Using this
      method, we clarify the role of the distribution of the input phase at discharge
      times. Finally, we argue that for large subthreshold inputs, mean discharge
      frequency locking accounts for the enhanced response.

PMID- 11969875
TI  - Soliton tunneling with sub-barrier kinetic energies.
AB  - We investigate (theoretically and numerically) the dynamics of a soliton moving
      in an asymmetrical potential well with a finite barrier. For large values of the
      width of the well, the width of the barrier, and/or the height of the barrier,
      the soliton behaves classically. On the other hand, we obtain the conditions for
      the existence of soliton tunneling with sub-barrier kinetic energies. We apply
      these results to the study of soliton propagation in disordered systems.

PMID- 11969876
TI  - Two-color nonlinear localized photonic modes.
AB  - We analyze second-harmonic generation (SHG) at a thin effectively quadratic
      nonlinear interface between two linear optical media. We predict multistability
      of SHG for both plane and localized waves, and also describe two-color localized
      photonic modes composed of a fundamental wave and its second harmonic coupled
      together by parametric interaction at the interface.

PMID- 11969877
TI  - Dark solitary waves in the nonlinear Schrodinger equation with third order
      dispersion, self-steepening, and self-frequency shift.
AB  - We solve the higher order nonlinear Schrodinger equation describing the
      propagation of ultrashort pulses in optical fibers. By means of the coupled
      amplitude-phase formulation fundamental (solitary wave) dark soliton solutions
      are found.

PMID- 11969878
TI  - Corrections to scaling in the phase-ordering dynamics of a vector order
      parameter.
AB  - Corrections to scaling, associated with deviations of the order parameter from
      the scaling morphology in the initial state, are studied for systems with O(n)
      symmetry at zero temperature in phase-ordering kinetics. Including corrections to
      scaling, the equal time pair correlation function has the form C(r,t)=f0(r/L)+L(
      omega)f1(r/L)+., where L is the coarsening length scale. The correction-to
      scaling exponent omega and the correction-to-scaling function f1(x) are
      calculated for both nonconserved and conserved order parameter systems using the
      approximate Gaussian closure theory of Mazenko. In general omega is a nontrivial
      exponent which depends on both the dimensionality d of the system and the number
      of components n of the order parameter. Corrections to scaling are also
      calculated for the nonconserved one-dimensional XY model, where an exact solution
      is possible.

PMID- 11969879
TI  - Generalization of Metropolis and heat-bath sampling for Monte Carlo simulations.
AB  - For a wide class of applications of the Monte Carlo method, we describe a general
      sampling methodology that is guaranteed to converge to a specified equilibrium
      distribution function. The method is distinct from that of Metropolis in that it
      is sometimes possible to arrange for unconditional acceptance of trial moves. It
      involves sampling states in a local region of phase space with probability equal
      to, in the first approximation, the square root of the desired global probability
      density function. The validity of this choice is derived from the Chapman
      Kolmogorov equation, and the utility of the method is illustrated by a
      prototypical numerical experiment.

PMID- 11969880
TI  - Breathers and multibreathers in a periodically driven damped discrete nonlinear
      Schrodinger equation.
AB  - We study an integrable discretization of the nonlinear Schrodinger equation (NLS)
      under the effects of damping and periodic driving, from the point of view of
      spatially localized solutions oscillating in time with the driver's frequency. We
      locate the equilibrium states of the discretized (DNLS) system in the plane of
      its dissipation gamma and forcing amplitude H parameters and use a shooting
      algorithm to construct the desired solutions psi(n)(t)=phi(n) exp(it) as
      homoclinic orbits of a four-dimensional symplectic map in the complex
      phi(n),phi(n+1) space, for -infinity<n<infinity. We derive, in the gamma=0 case,
      closed form expressions for two fundamental such solutions having a single hump
      in n, psi(n)+, and psi(n)-, and determine analytically their threshold of
      existence in the (gamma,H) plane using Mel'nikov's theory. Then, we demonstrate
      numerically that above this threshold a remarkable variety of multihump
      structures appear, whose complexity in terms of their spatial extrema grows with
      increasing H. All these solutions are numerically found to be unstable in time,
      except for psi(n)-, which is seen to be stable over a certain region in the
      (gamma,H) plane. In the continuum limit our results are in close agreement with
      recent studies on the NLS equation. From a more general perspective, we view
      these DNLS multihump solutions as homoclinic orbits of a higher-dimensional map
      thereby providing a possible mechanism for explaining the occurrence of similar
      structures called discrete (multi-) breathers found in a wide variety of one
      dimensional nonlinear lattices.

PMID- 11969881
TI  - Reaction diffusion models in one dimension with disorder.
AB  - We study a large class of one-dimensional reaction diffusion models with quenched
      disorder using a real space renormalization group method (RSRG) which yields
      exact results at large time. Particles (e.g., of several species) undergo
      diffusion with random local bias (Sinai model) and may react upon meeting. We
      obtain a detailed description of the asymptotic states (i.e., attractive fixed
      points of the RSRG), such as the large time decay of the density of each specie,
      their associated universal amplitudes, and the spatial distribution of particles.
      We also derive the spectrum of nontrivial exponents which characterize the
      convergence towards the asymptotic states. For reactions which lead to several
      possible asymptotic states separated by unstable fixed points, we analyze the
      dynamical phase diagram and obtain the critical exponents characterizing the
      transitions. We also obtain a detailed characterization of the persistence
      properties for single particles as well as more complex patterns. We compute the
      decay exponents for the probability of no crossing of a given point by,
      respectively, the single particle trajectories (theta) or the thermally averaged
      packets (theta). The generalized persistence exponents associated to n crossings
      are also obtained. Specifying to the process A+A--> or A with probabilities (r,1
      r), we compute exactly the exponents delta(r) and psi(r) characterizing the
      survival up to time t of a domain without any merging or with mergings,
      respectively, and the exponents deltaA(r) and psiA(r) characterizing the survival
      up to time t of a particle A without any coalescence or with coalescences,
      respectively. theta, psi, and delta obey hypergeometric equations and are
      numerically surprisingly close to pure system exponents (though associated to a
      completely different diffusion length). The effect of additional disorder in the
      reaction rates, as well as some open questions, are also discussed.

PMID- 11969882
TI  - Dynamical real space renormalization group applied to sandpile models.
AB  - A general framework for the renormalization group analysis of self-organized
      critical sandpile models is formulated. The usual real space renormalization
      scheme for lattice models when applied to nonequilibrium dynamical models must be
      supplemented by feedback relations coming from the stationarity conditions. On
      the basis of these ideas the dynamically driven renormalization group is applied
      to describe the boundary and bulk critical behavior of sandpile models. A
      detailed description of the branching nature of sandpile avalanches is given in
      terms of the generating functions of the underlying branching process.

PMID- 11969883
TI  - Polymorphic phase transitions in systems evolving in a two-dimensional discrete
      space.
AB  - Polymorphic phase transitions in systems evolving in a two-dimensional discrete
      space have been studied. The driving force of the transitions appears to be a
      difference between two main energetic contributions: one, related to the thermal
      activation of the process, and another, being of quantum nature. The former (high
      temperature limit) is naturally assigned to the expansion (melting) part of the
      transition, while the latter (low temperature limit) has much in common with the
      contraction (solidification) part. Between the two main physical states
      distinguished, there exists a certain state, corresponding to a discontinuity
      point (pole) in the morphological phase diagram, represented by the well-known
      Bose-Einstein (Planck) formula, in which the system blows up. This point is
      related to an expected situation in which the contour of the object under
      investigation stands for the Brownian or purely diffusional path, with the
      fractal dimension dw=2, and the situation can be interpreted as some emergence of
      an intermediate "tetratic" phase. This, in turn, recalls a certain analogy to the
      equilibrium (order-disorder) phase transition of Kosterlitz-Thouless type,
      characteristic of, e.g., rough vs rigid interfaces in a two-dimensional space,
      with some disappearance of interface correlation length at dw=2. Otherwise, the
      contours of the objects are equivalent to fractional Brownian paths either in
      superlinear or "turbulent" (dw<2; the expansion case), or sublinear, viz.,
      anomalously slow (dw>2; the contraction case) regimes, respectively. It is hoped
      that the description offered will serve to reflect properly the main subtleties
      of the dynamics of the polymorphic transitions in complex "soft-matter" systems,
      like formation of lipid mesomorphs or diffusional patterns, with nonzero line
      tension effect.

PMID- 11969884
TI  - Growth kinetics and morphology of a ballistic deposition model that incorporates
      surface diffusion for two species.
AB  - We introduce a ballistic deposition model for two kinds of particles (active and
      inactive) in (2+1) dimensions upon introducing surface diffusion for the inactive
      particles. A morphological structural transition is found as the probability of
      being the inactive particle increases. This transition is well defined by the
      change in the behavior of the surface width when it is plotted as a function of
      time and probability. The exponents alpha and beta calculated for different
      values of probability show the same behavior. The presence of both types of
      particles gives rise to three different processes that control the growing
      surface: overhanging, nonlocal growth, and diffusion. It finally leads to a
      morphological structural transition where the universality changes away from that
      of Kardar, Parisi, and Zhang, in (2+1) dimensions, but not into that of Edwards
      and Wilkinson.

PMID- 11969885
TI  - Wandering of a contact line at thermal equilibrium.
AB  - We reconsider the problem of the solid-liquid-vapor contact-line on a disordered
      substrate, in the collective pinning regime. We perform a replica variational
      calculation which confirms the scaling behavior obtained from Larkin-Imry-Ma-like
      arguments and provides a quantitative prediction for the correlation function of
      the line. This prediction is in good agreement with experimental findings for the
      case of superfluid helium on a caesium substrate.

PMID- 11969886
TI  - Atomic diffusion, step relaxation, and step fluctuations.
AB  - We show that the dynamics of the pair correlation function in a step train can
      pinpoint the dominant relaxation mechanism occurring at a crystal surface.
      Evaporation-condensation and step-edge diffusion do not produce dynamical
      correlations between neighboring steps, while terrace diffusion may lead to
      correlations which fall off like a power law with distance and which are peaked
      at a characteristic time. We derive these results within a "real space" Langevin
      formalism which is based on diffusion kernels which are different for each mass
      transport process. We validate this formalism by reproducing the step fluctuation
      autocorrelation function. We then derive results on the pair correlation between
      different steps. Results for solvable limiting cases are summarized in Tables I
      and II of the paper. As an intermediate step in the analysis we also find
      expressions for the relaxation time tau(pq) of a mode of wave number q along the
      steps and wave number p perpendicular to the steps, which we also discuss and
      compare with prior work.

PMID- 11969887
TI  - Propagator representation of anomalous diffusion: the orientational structure
      factor formalism in NMR.
AB  - The radial Fourier transform for the isotropic space with a fractal dimension is
      discussed. The moments of diffusive displacements with non-Gaussian propagators
      arising as solutions of fractional diffusion equations are calculated. The
      Fourier propagator is applied to NMR correlation and spectral density functions
      in context with the orientational structure factor formalism. It is shown that
      the low-frequency molecular fluctuations of liquids in porous media with strong
      or forced adsorption at surfaces are due to reorientations mediated by
      translational displacements caused by surface diffusion of the adsorbate
      molecules. In terms of this formalism, field-cycling NMR experiments provide
      information on the static and dynamic fractal dimensions related to surface
      diffusion. The experimental results for liquids in porous silica glass can be
      explained by a surface fractal dimension df=2.5, where the mean squared
      displacement scales as <r(2)(t)> proportional, variantt(2/dw) with dw=1
      (ballistic transport), if the surface population can exchange with the bulklike
      phase in the pores, and with dw=2, if the bulklike phase is frozen. The former
      dynamics is interpreted in terms of bulk-mediated surface diffusion.

PMID- 11969888
TI  - Power-law distributions and Levy-stable intermittent fluctuations in stochastic
      systems of many autocatalytic elements.
AB  - A generic model of stochastic autocatalytic dynamics with many degrees of freedom
      w(i,) i=1, em leader,N, is studied using computer simulations. The time evolution
      of the w(i)'s combines a random multiplicative dynamics w(i)(t+1)=lambdaw(i)(t)
      at the individual level with a global coupling through a constraint which does
      not allow the w(i)'s to fall below a lower cutoff given by cw, where w is their
      momentary average and 0<c<1 is a constant. The dynamic variables w(i) are found
      to exhibit a power-law distribution of the form p(w) approximately w(-1-alpha).
      The exponent alpha(c,N) is quite insensitive to the distribution Pi(lambda) of
      the random factor lambda, but it is nonuniversal, and increases monotonically as
      a function of c. The "thermodynamic" limit N-->infinity and the limit of
      decoupled free multiplicative random walks c-->0 do not commute: alpha(0,N)=0 for
      any finite N while alpha(c,infinity)>or=1 (which is the common range in empirical
      systems) for any positive c. The time evolution of w(t) exhibits intermittent
      fluctuations parametrized by a (truncated) Levy-stable distribution L(alpha)(r)
      with the same index alpha. This nontrivial relation between the distribution of
      the wi's at a given time and the temporal fluctuations of their average is
      examined, and its relevance to empirical systems is discussed.

PMID- 11969889
TI  - Diffusion in discrete ratchets.
AB  - The phenomenon of noise-induced transport in ratchet devices offers an
      explanation for directed motion on the molecular scale observed in many
      biological systems. Net transport through a series of discrete states, occurring
      in cyclic processes or reactions, can be related to widely investigated
      continuous ratchet models in the context of thermally activated transitions. The
      transport process can be described effectively in terms of two characteristic
      coefficients: velocity and diffusion. Their relation to model parameters and
      limitations for the ratchet mechanism are discussed in this paper. As an
      application we consider a four-state model for uphill transmembrane transport and
      compare theoretical results with existing data from a related experiment.

PMID- 11969890
TI  - Diffusion in lattice Lorentz gases with a percolation threshold.
AB  - A mean-field approximation for the diffusion coefficient in lattice Lorentz gases
      with an arbitrary mixture of pointlike stochastic scatterers in the low-density
      limit is proposed. In this approximation, the diffusion coefficient is directly
      related to the first return probability of the moving particle in the
      corresponding Cayley tree through an effective ring operator. A renormalization
      scheme for the approximate determination of the first return probability is
      constructed. The predictions of this mean-field theory and those of the repeated
      ring approximation (RRA) are compared with computer simulation results for models
      in which a fraction x(B) of the scatterers are deterministic backscatterers, so
      that the diffusion coefficient vanishes beyond a certain percolation threshold
      x(c)(B). The approximation proposed in this paper is seen to be in good agreement
      with the simulation results, in contrast to the RRA, which already fails to give
      the correct percolation threshold.

PMID- 11969891
TI  - Resonant activations for a fluctuating barrier system driven by dichotomous noise
      and Gaussian white noise.
AB  - We consider the escape over a fluctuating barrier in the presence of a
      dichotomous noise and a Gaussian white noise. It is shown that the mean first
      passage time (MFPT) over the fluctuating barrier displays two resonant
      activations. One is the resonant activation of the MFPT as a function of the
      flipping rate of the fluctuating potential barrier; the other is the resonant
      activation of the MFPT as a function of the transition rate of the dichotomous
      noise. In addition, we find that the dichotomous noise can weaken the former
      resonant activation, but enhance the latter one. By further study, we find that,
      when the fluctuating potential barrier is driven by two or more dichotomous
      noises, there are three or more resonant activations.

PMID- 11969892
TI  - Roughening transition of a restricted solid-on-solid model in the directed
      percolation universality class.
AB  - We carried out a finite-size scaling analysis of the restricted solid-on-solid
      version of a recently introduced growth model that exhibits a roughening
      transition accompanied by spontaneous symmetry breaking. The dynamic critical
      exponent of the model was calculated and found to be consistent with the
      universality class of the directed percolation process in a symmetry-broken phase
      with a crossover to Kardar-Parisi-Zhang behavior in a rough phase. The order
      parameter of the roughening transition together with the string order parameter
      was calculated, and we found that the flat, gapped phase is disordered with an
      antiferromagnetic spin-fluid structure of kinks, although strongly dominated by
      the completely flat configuration without kinks. A possible interesting extension
      of the model is mentioned.

PMID- 11969893
TI  - High resolution description of a crack front in a heterogeneous Plexiglas block.
AB  - We study experimentally the propagation of an in-plane fracture into a
      transparent and heterogeneous Plexiglas block. A stable crack propagation in mode
      I is monitored by an imposed displacement. The experimental setup allows a high
      resolution observation of the crack front in situ. Self-affine properties of the
      crack front are described over more than three decades using several techniques:
      variable bandwidth, return probability, Fourier spectrum, and wavelet analysis.
      The different methods lead to a roughness exponent of 0.63+/-0.03, consistent
      with a previous work.

PMID- 11969894
TI  - Universal critical coupling constants for the three-dimensional n-vector model
      from field theory.
AB  - The field-theoretical renormalization group (RG) approach in three dimensions is
      used to estimate the universal critical values of renormalized coupling constants
      g6 and g8 for the O(n)-symmetric model. The RG series for g6 and g8 are
      calculated in the four- and three-loop approximations, respectively, and then
      resummed by means of the Pade-Borel-Leroy technique. Under the optimal value of
      the shift parameter b providing the fastest convergence of the iteration
      procedure, numerical estimates for g*6 are obtained with an accuracy no worse
      than 0.3%. The RG expansion for g8 demonstrates a stronger divergence, and
      results in considerably cruder numerical estimates.

PMID- 11969895
TI  - Analysis of spatiotemporal signals: a method based on perturbation theory.
AB  - We present a method of analyzing spatiotemporal signals with respect to its
      underlying dynamics. The algorithm aims at the determination of spatial modes and
      a criterion for the number of interacting modes. Simultaneously, a way of
      filtering of nonorthogonal noise is shown. The method is discussed by examples of
      simulated stable fixpoints and the Lorenz attractor.

PMID- 11969896
TI  - Spinodals, scaling, and ergodicity in a threshold model with long-range stress
      transfer.
AB  - We present both theoretical and numerical analyses of a cellular automaton
      version of a slider-block model or threshold model that includes long-range
      interactions. Theoretically we develop a coarse-grained description in the mean
      field (infinite range) limit and discuss the relevance of the metastable state,
      limit of stability (spinodal), and nucleation to the phenomenology of the model.
      We also simulate the model and confirm the relevance of the theory for systems
      with long- but finite-range interactions. Results of particular interest include
      the existence of Gutenberg-Richter-like scaling consistent with that found on
      real earthquake fault systems, the association of large events with nucleation
      near the spinodal, and the result that such systems can be described, in the mean
      field limit, with techniques appropriate to systems in equilibrium.

PMID- 11969897
TI  - Trichotomous noise-induced transitions.
AB  - A nonlinear one-dimensional process driven by a multiplicative exponentially
      correlated three-level Markovian noise (trichotomous noise) is considered. An
      explicit second-order linear ordinary differential equation for the stationary
      probability density distribution is obtained for the process. In the case of a
      linear process with an additive trichotomous noise the exact formula for the
      steady-state distribution is obtained. The well-known dichotomous noise can be
      regarded as a special case of the trichotomous noise. As a rule, the system
      variable has three specific values where the probability density distribution can
      be singular. For the case of the Hongler model the dependence of the behavior of
      the stationary probability density on the noise parameters is investigated in
      detail and illustrated by a phase diagram. Applications to the Gompertz and
      Verhulst models are also discussed.

PMID- 11969898
TI  - Diffusion of particles moving with constant speed.
AB  - The propagation of light in a scattering medium is described as the motion of a
      special kind of a Brownian particle on which the fluctuating forces act only
      perpendicular to its velocity. This enforces strictly and dynamically the
      constraint of constant speed of the photon in the medium. A Fokker-Planck
      equation is derived for the probability distribution in the phase space assuming
      the transverse fluctuating force to be a white noise. Analytic expressions for
      the moments of the displacement <x(n)> along with an approximate expression for
      the marginal probability distribution function P(x,t) are obtained. Exact
      numerical solutions for the phase space probability distribution for various
      geometries are presented. The results show that the velocity distribution
      randomizes in a time of about eight times the mean free time (8t*) only after
      which the diffusion approximation becomes valid. This factor of 8 is a well-known
      experimental fact. A persistence exponent of 0.435+/-0.005 is calculated for this
      process in two dimensions by studying the survival probability of the particle in
      a semi-infinite medium. The case of a stochastic amplifying medium is also
      discussed.

PMID- 11969899
TI  - Statistical properties of the volatility of price fluctuations.
AB  - We study the statistical properties of volatility, measured by locally averaging
      over a time window T, the absolute value of price changes over a short time
      interval deltat. We analyze the S&P 500 stock index for the 13-year period Jan.
      1984 to Dec. 1996. We find that the cumulative distribution of the volatility is
      consistent with a power-law asymptotic behavior, characterized by an exponent mu
      approximately 3, similar to what is found for the distribution of price changes.
      The volatility distribution retains the same functional form for a range of
      values of T. Further, we study the volatility correlations by using the power
      spectrum analysis. Both methods support a power law decay of the correlation
      function and give consistent estimates of the relevant scaling exponents. Also,
      both methods show the presence of a crossover at approximately 1.5 days. In
      addition, we extend these results to the volatility of individual companies by
      analyzing a data base comprising all trades for the largest 500 U.S. companies
      over the two-year period Jan. 1994 to Dec. 1995.

PMID- 11969900
TI  - Thermostating by deterministic scattering: heat and shear flow.
AB  - We apply a recently proposed thermostating mechanism to an interacting many
      particle system where the bulk particles are moving according to Hamiltonian
      dynamics. At the boundaries the system is thermalized by deterministic and time
      reversible scattering. We first show how this scattering mechanism can be related
      to stochastic boundary conditions. We subsequently simulate thermal conduction
      and shear flow for a hard disk fluid. By comparing the transport coefficients
      obtained from computer simulations to theoretical results we find that this
      thermostating mechanism yields well-defined nonequilibrium steady states in the
      range of linear response. Furthermore, the conjectured identity between
      thermodynamic entropy production and exponential phase-space contraction rates is
      investigated from the standpoint of our formalism. We find that, in general,
      these quantities do not agree.

PMID- 11969901
TI  - Highly optimized tolerance: a mechanism for power laws in designed systems.
AB  - We introduce a mechanism for generating power law distributions, referred to as
      highly optimized tolerance (HOT), which is motivated by biological organisms and
      advanced engineering technologies. Our focus is on systems which are optimized,
      either through natural selection or engineering design, to provide robust
      performance despite uncertain environments. We suggest that power laws in these
      systems are due to tradeoffs between yield, cost of resources, and tolerance to
      risks. These tradeoffs lead to highly optimized designs that allow for occasional
      large events. We investigate the mechanism in the context of percolation and sand
      pile models in order to emphasize the sharp contrasts between HOT and self
      organized criticality (SOC), which has been widely suggested as the origin for
      power laws in complex systems. Like SOC, HOT produces power laws. However,
      compared to SOC, HOT states exist for densities which are higher than the
      critical density, and the power laws are not restricted to special values of the
      density. The characteristic features of HOT systems include: (1) high efficiency,
      performance, and robustness to designed-for uncertainties; (2) hypersensitivity
      to design flaws and unanticipated perturbations; (3) nongeneric, specialized,
      structured configurations; and (4) power laws. The first three of these are in
      contrast to the traditional hallmarks of criticality, and are obtained by simply
      adding the element of design to percolation and sand pile models, which
      completely changes their characteristics.

PMID- 11969902
TI  - Functional integration approach to hysteresis.
AB  - A general formulation of scalar hysteresis is proposed. This formulation is based
      on two steps. First, a generating function g(x) is associated with an individual
      system, and a hysteresis evolution operator is defined by an appropriate envelope
      construction applied to g(x), inspired by the overdamped dynamics of systems
      evolving in multistable free-energy landscapes. Second, the average hysteresis
      response of an ensemble of such systems is expressed as a functional integral
      over the space G of all admissible generating functions, under the assumption
      that an appropriate measure mu has been introduced in G. The consequences of the
      formulation are analyzed in detail in the case where the measure mu is generated
      by a continuous, Markovian stochastic process. The calculation of the hysteresis
      properties of the ensemble is reduced to the solution of the level-crossing
      problem for the stochastic process. In particular, it is shown that, when the
      process is translationally invariant (homogeneous), the ensuing hysteresis
      properties can be exactly described by the Preisach model of hysteresis, and the
      associated Preisach distribution is expressed in closed analytic form in terms of
      the drift and diffusion parameters of the Markovian process. Possible
      applications of the formulation are suggested, concerning the interpretation of
      magnetic hysteresis due to domain wall motion in quenched-in disorder and the
      interpretation of critical state models of superconducting hysteresis.

PMID- 11969903
TI  - Microscopic analysis of currency and stock exchange markets.
AB  - Recently it was shown that distributions of short-term price fluctuations in
      foreign-currency exchange exhibit striking similarities to those of velocity
      differences in turbulent flows. Similar profiles represent the spectral-diffusion
      behavior of impurity molecules in disordered solids at low temperatures. It is
      demonstrated that a microscopic statistical theory of the spectroscopic line
      shapes can be applied to the other two phenomena. The theory interprets the
      financial data in terms of information which becomes available to the traders and
      their reactions as a function of time. The analysis shows that there is no
      characteristic time scale in financial markets, but that instead stretched
      exponential or algebraic memory functions yield good agreement with the price
      data. For an algebraic function, the theory yields truncated Levy distributions
      which are often observed in stock exchange markets.

PMID- 11969904
TI  - Binary data corruption due to a Brownian agent. II. Two dimensions, competing
      agents, and generalized couplings.
AB  - This work is a continuation of our previous investigation of binary data
      corruption due to a Brownian agent [Phys. Rev. E 59, 5172 (1999)]. We extend our
      study in three main directions which allow us to make closer contact with real
      bistable systems. These are (i) a detailed analysis of two dimensions, (ii) the
      case of competing agents, and (iii) the cases of asymmetric and quenched random
      couplings. Most of our results are obtained by extending our original
      phenomenological model, and are supported by extensive numerical simulations.

PMID- 11969905
TI  - Analytical results for random walks in the presence of disorder and traps.
AB  - In this paper, we study the dynamics of a random walker diffusing on a disordered
      one-dimensional lattice with random trappings. The distribution of escape
      probabilities is computed exactly for any strength of the disorder. These
      probabilities do not display any multifractal properties, contrary to previous
      numerical claims. The explanation for this apparent multifractal behavior is
      given, and our conclusions are supported by numerical calculations. These exact
      results are exploited to compute the large time asymptotics of the survival
      probability (or the density) which is found to decay as exp[-Ct(1/3)ln(2/3)(t)].
      An exact lower bound for the density is found to decay in a similar way.

PMID- 11969906
TI  - Transient nonlinear dielectric relaxation and dynamic Kerr effect from sudden
      changes of a strong dc electric field: polar and polarizable molecules.
AB  - The nonlinear transient response of polar and polarizable particles
      (macromolecules) diluted in a nonpolar solvent to a sudden change both in
      magnitude and in direction of a strong external dc field is considered. By
      averaging the underlying Langevin equation, the infinite hierarchy of
      differential-recurrence equations for ensemble averages of the spherical
      harmonics is derived for an assembly of polar and anisotropically polarizable
      molecules pertaining to the noninertial rotational Brownian motion. On solving
      this hierarchy, the relaxation functions and relaxation times appropriate to the
      transient dynamic Kerr effect and nonlinear dielectric relaxation are calculated.
      The calculations are accomplished using the matrix continued fraction method,
      which allows us to express exactly the solution of the infinite hierarchy of
      differential-recurrence relations for the first- and second-order transient
      responses of the ensemble averages of the spherical harmonics (relaxation
      functions). The results are then compared with available experimental data and
      solutions previously obtained for various particular cases.

PMID- 11969907
TI  - Possible experimental measure theory for the XXX-Heisenberg chain.
AB  - Raising and lowering operators for the XXX-Heisenberg chain are derived
      explicitly; as a result the dipole moment operator is established. Based on the
      dipole transition mechanism in an external time-dependent magnetic field, we
      propose a possible experimental measure theory to detect the energy spectrum of
      the spin chain.

PMID- 11969908
TI  - Stochastic resonance in linear systems subject to multiplicative and additive
      noise.
AB  - Exact expressions have been found for the first two moments and the correlation
      function for an overdamped linear system subject to an external periodic field as
      well as to multiplicative and additive noise. Stochastic resonance is absent for
      Gaussian white noise. However, when the multiplicative noise has the form of an
      asymmetric dichotomous noise, the signal-to-noise ratio (SNR) becomes a
      nonmonotonic function of the correlation time and the asymmetry of noise.
      Moreover, the SNR turns out to be a nonmonotonic function of the frequency of the
      external field as well as strongly depending on the strength of the cross
      correlation between multiplicative and additive noise.

PMID- 11969909
TI  - Inverse Mermin-Wagner theorem for classical spin models on graphs.
AB  - In this paper we present the inversion of the Mermin-Wagner theorem on graphs, by
      proving the existence of spontaneous magnetization at finite temperature for
      classical spin models on transient on the average graphs, i.e., graphs where a
      random walker returns to its starting point with an average probability F<1. This
      result, which is here proven for models with O(n) symmetry, includes as a
      particular case n=1, providing a very general condition for spontaneous symmetry
      breaking on inhomogeneous structures even for the Ising model.

PMID- 11969910
TI  - Orientational relaxation in Brownian rotors with frustrated interactions on a
      square lattice.
AB  - We present simulation results on the equilibrium relaxation of Brownian planar
      rotors based on a uniformly frustrated XY model on a square lattice. The
      rotational relaxation exhibits typical dynamic features of fragile supercooled
      liquids including the two-step relaxation. We observe a dynamic crossover from
      the high-temperature regime with Arrhenius behavior to the low-temperature regime
      with temperature-dependent activation energy. A consistent picture for the
      observed slow dynamics can be given in terms of the caging effect and thermal
      activation across potential barriers in the energy landscapes.

PMID- 11969911
TI  - Spontaneous spiral formation in two-dimensional oscillatory media.
AB  - Computational studies of pattern formation in a modified Oregonator model of the
      Belousov-Zhabotinsky reaction is described. Initially inactive two-dimensional
      reaction media with an immobilized catalyst is connected to a reservoir of fresh
      reactants through a set of discrete points distributed randomly over the
      interphase surface. It is shown that the diffusion of reactants combined with
      oscillatory reaction kinetics can give rise to spontaneous spiral formation and
      phase waves.

PMID- 11969913
TI  - Thermodynamic framework for discrete optimal control in multiphase flow systems.
AB  - Bellman's method of dynamic programming is used to synthesize diverse
      optimization approaches to active (work producing) and inactive (entropy
      generating) multiphase flow systems. Thermal machines, optimally controlled unit
      operations, nonlinear heat conduction, spontaneous relaxation processes, and self
      propagating wave fronts are all shown to satisfy a discrete Hamilton-Jacobi
      Bellman equation and a corresponding discrete optimization algorithm of
      Pontryagin's type, with the maximum principle for a Hamiltonian. The extremal
      structures are always canonical. A common unifying criterion is set for all
      considered systems, which is the criterion of a minimum generated entropy. It is
      shown that constraints can modify the entropy functionals in a different way for
      each group of the processes considered; thus the resulting structures of these
      functionals may differ significantly. Practical conclusions are formulated
      regarding the energy savings and energy policy in optimally controlled systems.

PMID- 11969912
TI  - Model of biological evolution with threshold dynamics and infinitely many
      absorbing states.
AB  - We study a model of biological evolution where the survival of a given species
      depends on its interactions with neighboring species. In the steady state the
      model has an active phase and an absorbing phase, which are separated by the
      critical point of the directed percolation universality class. The absorbing
      phase is infinitely degenerate and the dynamical behavior of our model is found
      to be nonuniversal.

PMID- 11969914
TI  - Chaotic jam and phase transition in traffic flow with passing.
AB  - The lattice hydrodynamic model is presented to take into account the passing
      effect in one-dimensional traffic flow. When the passing constant gamma is small,
      the conventional jamming transition occurs between the uniform traffic and kink
      density wave flows. When passing constant gamma is larger than the critical
      value, the jamming transitions occur from the uniform traffic flow, through the
      chaotic density wave flow, to the kink density wave flow, with an increasing
      delay time. The chaotic region increases with passing constant gamma. The neutral
      stability line is derived from the linear stability analysis. The neutral
      stability line coincides with the transition line between the uniform traffic and
      density wave flows. The modified Korteweg-de Vries equation describing the kink
      jam is derived for small values of gamma by use of a nonlinear analysis.

PMID- 11969915
TI  - Signatures of chaos in the entanglement of two coupled quantum kicked tops.
AB  - We investigate the rate at which two initially decoupled quantum kicked tops
      become entangled upon the introduction of an interaction between them. We find
      that the entanglement eventually increases linearly in time. Moreover, we find
      that the rate of this linear increase is itself a linear function of the sum of
      the positive Lyapunov exponents when averaged over initial points drawn from the
      classical distributions corresponding to the initial quantum product state. The
      entanglement measure that is used allows us to identify entanglement with
      sensitive dependence on initial conditions.

PMID- 11969916
TI  - Semiconductor laser with optical feedback: from excitable to deterministic low
      frequency fluctuations.
AB  - Semiconductor lasers with optical feedback present a regime in which power
      dropouts are observed. Although this regime has been extensively studied, there
      is no agreement about whether the dropouts are deterministically or
      stochastically generated. In this paper we will study the statistics of time
      intervals between dropouts assuming noise-driven simple excitable models. We
      explain the appearance of characteristic times in the first return maps.

PMID- 11969917
TI  - Transient fractal behavior in snapshot attractors of driven chaotic systems.
AB  - Snapshot attractors, i.e., attractors formed by a cloud of trajectories at the
      same instants of time, are usually employed to reveal the fractal structure of
      randomly or chaotically driven dynamical systems. A necessary condition for the
      underlying fractal structure to be observed is that the ensemble of particles
      utilized in the construction of the snapshot attractors are subject to identical
      perturbation at any instant of time. We examine the influence of small phase
      space inhomogeneity in the chaotic perturbation on the observability of the
      snapshot fractal attractors. We find that, typically, fractal structure can be
      seen in only a transient period of time. The scaling of the transient time with
      the amount of inhomogeneity is investigated. Implication to experimental
      observation of fractal structure in physical systems is pointed out.

PMID- 11969918
TI  - Estimating the Lyapunov spectrum of time delay feedback systems from scalar time
      series.
AB  - On the basis of a recently developed method for modeling time delay systems, we
      propose a procedure to estimate the spectrum of Lyapunov exponents from a scalar
      time series. It turns out that the spectrum is approximated very well and allows
      for good estimates of the Lyapunov dimension even if the sampling rate of the
      time series is so low that the infinite dimensional tangent space is spanned
      quite sparsely.

PMID- 11969919
TI  - Noise-induced phase space transport in two-dimensional Hamiltonian systems.
AB  - First passage time experiments were used to explore the effects of low amplitude
      noise as a source of accelerated phase space diffusion in two-dimensional
      Hamiltonian systems, and these effects were then compared with the effects of
      periodic driving. The objective was to quantify and understand the manner in
      which "sticky" chaotic orbits that, in the absence of perturbations, are confined
      near regular islands for very long times, can become "unstuck" much more quickly
      when subjected to even very weak perturbations. For both noise and periodic
      driving, the typical escape time scales logarithmically with the amplitude of the
      perturbation. For white noise, the details seem unimportant: Additive and
      multiplicative noise typically have very similar effects, and the presence or
      absence of a friction related to the noise by a fluctuation-dissipation theorem
      is also largely irrelevant. Allowing for colored noise can significantly decrease
      the efficacy of the perturbation, but only when the autocorrelation time, which
      vanishes for white noise, becomes so large that there is little power at
      frequencies comparable to the natural frequencies of the unperturbed orbit.
      Similarly, periodic driving is relatively inefficient when the driving frequency
      is not comparable to these natural frequencies. This suggests that noise-induced
      extrinsic diffusion, like modulational diffusion associated with periodic
      driving, is a resonance phenomenon. The logarithmic dependence of the escape time
      on amplitude reflects the fact that the time required for perturbed and
      unperturbed orbits to diverge a given distance scales logarithmically in the
      amplitude of the perturbation.

PMID- 11969920
TI  - Mutual synchronization and clustering in randomly coupled chaotic dynamical
      networks.
AB  - We introduce and study systems of randomly coupled maps where the relevant
      parameter is the degree of connectivity in the system. Global (almost-)
      synchronized states are found (equivalent to the synchronization observed in
      globally coupled maps) until a certain critical threshold for the connectivity is
      reached. We further show that not only the average connectivity, but also the
      architecture of the couplings is responsible for the cluster structure observed.
      We analyze the different phases of the system and use various correlation
      measures in order to detect ordered nonsynchronized states. Finally, it is shown
      that the system displays a dynamical hierarchical clustering which allows the
      definition of emerging graphs.

PMID- 11969921
TI  - Pauli principle and chaos in a magnetized disk.
AB  - We present results of a detailed quantum-mechanical study of a gas of N
      noninteracting electrons confined to a circular boundary and subject to
      homogeneous dc plus ac magnetic fields [B=B(dc)+B(ac)f(t), with
      f(t+2pi/omega(0))=f(t)]. We earlier found a one-particle classical phase diagram
      of the (scaled) Larmor frequency omega;(c)=omega(c)/omega(0) vs
      epsilon=B(ac)/B(dc) that separates regular from chaotic regimes. We also showed
      that the quantum spectrum statistics changed from Poisson to Gaussian orthogonal
      ensembles in the transition from classically integrable to chaotic dynamics. Here
      we find that, as a function of N and (epsilon,omega(c)), there are clear quantum
      signatures in the magnetic response, when going from the single-particle
      classically regular to chaotic regimes. In the quasi-integrable regime the
      magnetization nonmonotonically oscillates between diamagnetic and paramagnetic as
      a function of N. We quantitatively understand this behavior from a perturbation
      theory analysis. In the chaotic regime, however, we find that the magnetization
      oscillates as a function of N but it is always diamagnetic. Equivalent results
      are also presented for the orbital currents. We also find that the time-averaged
      energy grows as N2 in the quasi-integrable regime but changes to a linear N
      dependence in the chaotic regime. In contrast, the results with Bose statistics
      are akin to the single-particle case and thus different from the fermionic case.
      We also give an estimate of possible experimental parameters where our results
      may be seen in semiconductor quantum dot billiards.

PMID- 11969922
TI  - Structure selection for global vector field reconstruction by using the
      identification of fixed points.
AB  - Global vector field reconstruction is a well established technique to provide
      phenomenological models from nonlinear data, in particular when all information
      is contained in a so-called standard function. In the case when the standard
      function is taken as a ratio of polynomials, we establish that information about
      the fixed points of the system can be automatically retrieved from the data,
      allowing one to build a better model by selecting an appropriate structure. The
      method is exemplified in the case of the variable z of the Rossler system, which
      constitutes a rather acid test case.

PMID- 11969923
TI  - Classical and quantum chaos in a circular billiard with a straight cut.
AB  - We study classical and quantum dynamics of a particle in a circular billiard with
      a straight cut. Classically, this system can be integrable, nonintegrable with
      soft chaos, or nonintegrable with hard chaos as we vary the size of the cut. We
      plot Poincare surfaces of section to study chaos. Quantum mechanically, we look
      at Husimi plots, and also use the quantum web, the technique primarily used in
      spin systems so far, to try to see differences in quantum manifestations of soft
      and hard chaos.

PMID- 11969924
TI  - Multidimensional quasiperiodic antiphase dynamics.
AB  - We study analytically the (N-1)-fold degenerate Hopf bifurcation at which N
      stationary modes with identical parameters become unstable in a model of a solid
      state laser with intracavity second harmonic generation. We use the normal form
      method and exploit the symmetries of the problem. Up to N=3, stable periodic
      antiphased solutions emerge from the Hopf bifurcation. For N=4, stable
      quasiperiodic solutions arise from the degenerate Hopf bifurcation. For N>4, the
      quasiperiodic solutions may be unstable. Then chaotic itineracy is observed
      numerically close to the degenerate Hopf bifurcation.

PMID- 11969925
TI  - Semiclassical non-trace-type formulas for matrix-element fluctuations and
      weighted densities of states.
AB  - Densities of states weighted with the diagonal matrix elements of two operators A
      and B, i.e., rho(A,B)(E)= summation operator(n)<nAn><nBn>delta(E-E(n)), cannot,
      in general, be written as a trace formula, and therefore no simple extension of
      semiclassical trace formulas is known for this case. However, from the high
      resolution analysis of quantum spectra in the semiclassical regime we find strong
      evidence that weighting the delta functions in the quantum mechanical density of
      states with the product of diagonal matrix elements, <nAn><nBn>, is equivalent to
      weighting the periodic orbit contributions in the semiclassical periodic orbit
      sum with the product of the periodic orbit means, <A>(p)<B>(p), of the classical
      observables A and B. Results are presented for the hydrogen atom in a magnetic
      field for both the chaotic and near-integrable regime, and for the circle
      billiard.

PMID- 11969926
TI  - Semiclassical spectra and diagonal matrix elements by harmonic inversion of cross
      correlated periodic orbit sums.
AB  - Semiclassical spectra weighted with products of diagonal matrix elements of
      operators A(alpha), i.e., g(alphaalpha')(E)= summation
      operator(n)<nA(alpha)n><nA(alpha')n>/(E-E(n)), are obtained by harmonic inversion
      of a cross-correlation signal constructed of classical periodic orbits. The
      method provides highly resolved semiclassical spectra even in situations of
      nearly degenerate states, and opens the way to reducing the required signal
      lengths to shorter than the Heisenberg time. This implies a significant reduction
      of the number of orbits required for periodic orbit quantization by harmonic
      inversion.

PMID- 11969927
TI  - Decoherence and correspondence in conservative chaotic dynamics.
AB  - The quantum and classical dynamics of a conservative nonlinear Hamiltonian system
      in the chaotic regime are compared in the absence and presence of decoherence
      effects. Results show marked improvement in classical-quantum correspondence with
      the introduction of decoherence, even though the initial quantum dynamics is far
      from the semiclassical limit.

PMID- 11969928
TI  - Multichannel digital communications by the synchronization of globally coupled
      chaotic systems.
AB  - A multichannel digital communication method using the synchronization of globally
      coupled chaotic systems is proposed. The proposed method allows several binary
      messages to be transmitted simultaneously by just one transmitted chaotic signal,
      provided that outputs of different units are uncorrelated. We demonstrate the
      communication method on a model system consisting of Lorenz-like units. We also
      show how to systematically construct high-dimensional synchronizing units, based
      on the idea of cascaded systems. Furthermore, the dynamics of the coupled chaotic
      systems is discussed with particular attention paid to the correlation between
      the motions of different units.

PMID- 11969929
TI  - Map from one-dimensional quantum field theory to quantum chaos on a two
      dimensional torus.
AB  - Dynamics of a class of quantum field models on a one-dimensional (1D) lattice in
      a Heisenberg picture is mapped onto a class of quantum chaotic one-body systems
      on a configurational 2D torus (or 2D lattice) in the Schrodinger picture. The
      continuum field limit of the former corresponds to the quasiclassical limit of
      the latter.

PMID- 11969930
TI  - Levy-nearest-neighbors Bak-Sneppen model.
AB  - We study a random neighbor version of the Bak-Sneppen model, where "nearest
      neighbors" are chosen according to a probability distribution decaying as a power
      law of the distance from the active site, P(x) approximately x-x(ac)(-omega). All
      of the exponents characterizing the self-organized critical state of this model
      depend on the exponent omega. As omega-->1 we recover the usual random nearest
      neighbor version of the model. The pattern of results obtained for a range of
      values of omega is also compatible with the results of simulations of the
      original BS model in high dimensions. Moreover, our results suggest a critical
      dimension dc=6 for the Bak-Sneppen model, in contrast with previous claims.

PMID- 11969931
TI  - Sign-time distributions for interface growth.
AB  - We apply the recently introduced distribution of sign-times (DST) to
      nonequilibrium interface growth dynamics. We are able to treat within a unified
      picture the persistence properties of a large class of relaxational and noisy
      linear growth processes, and prove the existence of a nontrivial scaling
      relation. A critical dimension is found, relating to the persistence properties
      of these systems. We also illustrate, by means of numerical simulations, the
      different types of DST to be expected in both linear and nonlinear growth
      mechanisms.

PMID- 11969932
TI  - Characterization and control of small-world networks.
AB  - Recently, Watts and Strogatz [Nature (London) 393, 440 (1998)] offered an
      interesting model of small-world networks. Here we concretize the concept of a
      "faraway" connection in a network by defining a far edge. Our definition is
      algorithmic and independent of any external parameters such as topology of the
      underlying space of the network. We show that it is possible to control the
      spread of an epidemic by using the knowledge of far edges. We also suggest a
      model for better product advertisement using the far edges. Our findings indicate
      that the number of far edges can be a good intrinsic parameter to characterize
      small-world phenomena.

PMID- 11969933
TI  - Scaling for the critical percolation backbone.
AB  - We study the backbone connecting two given sites of a two-dimensional lattice
      separated by an arbitrary distance r in a system of size L at the percolation
      threshold. We find a scaling form for the average backbone mass: <M(B)>
      approximately L(dB)G(r/L), where G can be well approximated by a power law for
      0<or=x<or=1: G(x) approximately x(psi) with psi=0.37+/-0.02. This result implies
      that <M(B)> approximately L(dB-psi)r(psi) for the entire range 0<r<L. We also
      propose a scaling form for the probability distribution P(M(B)) of backbone mass
      for a given r. For r approximately L, P(MB) is peaked around L(dB), whereas for
      r<<L, P(M(B)) decreases as a power law, M(-tauB)B, with tauB approximately 1.20+/
      0.03. The exponents psi and tauB satisfy the relation psi=dB(tauB-1), and psi is
      the codimension of the backbone, psi=d-dB.

PMID- 11969934
TI  - Alternative algorithm for the computation of Lyapunov spectra of dynamical
      systems.
AB  - Recently a new method for the computation of Lyapunov exponents that does not
      require rescaling and reorthogonalization was proposed [Rangarajan, Habib, and
      Ryne, Phys. Rev. Lett. 80, 3747 (1998)]. In this paper we make a detailed
      numerical comparison of the new method and a standard algorithm, as regards
      accuracy and efficiency, by applying them to some typical two-, three-, and four
      dimensional systems. We find that in most cases there is reasonable agreement
      between the Lyapunov spectra obtained using the two algorithms. The CPU times
      required for computation are also comparable. However, in certain strongly
      chaotic cases, the new method was found to be either inefficient (taking a lot of
      CPU time for computation) or inaccurate.

PMID- 11969935
TI  - Origin of coherent structures in a discrete chaotic medium.
AB  - Using as an example a large lattice of locally interacting Hindmarsh-Rose chaotic
      neurons, we disclose the origin of ordered structures in a discrete
      nonequilibrium medium with fast and slow chaotic oscillations. The origin of the
      ordering mechanism is related to the appearance of a periodic average dynamics in
      the group of chaotic neurons whose individual slow activity is significantly
      synchronized by the group mean field. Introducing the concept of a "coarse grain"
      as a cluster of neuron elements with periodic averaged behavior allows
      consideration of the dynamics of a medium composed of these clusters. A study of
      this medium reveals spatially ordered patterns in the periodic and slow dynamics
      of the coarse grains that are controlled by the average intensity of the fast
      chaotic pulsation.

PMID- 11969936
TI  - Intrinsic localized modes and chaos in damped driven rotator lattices.
AB  - It is shown that intrinsic localized rotational modes (ILRMs) in parametrically
      driven damped lattices of coupled classical dipole rotators can become chaotic
      without losing their localized character. Insight into this behavior is obtained
      by means of a nonlinear stability analysis. Moreover, we discuss a robust scheme
      for exploiting a spatially extended chaotic state to generate stationary randomly
      spaced arrays of driven ILRMs, and show that the associated absorption exhibits
      unusual signatures.

PMID- 11969937
TI  - Passive scalar intermittency in compressible flow.
AB  - A compressible generalization of the Kraichnan model [Phys. Rev. Lett. 72, 1016
      (1994)] of passive scalar advection is considered. The dynamical role of
      compressibility on the intermittency of the scalar statistics is investigated for
      the direct cascade regime. Simple physical arguments suggest that an enhanced
      intermittency should appear for increasing compressibility, due to the slowing
      down of Lagrangian trajectory separations. This is confirmed by a numerical study
      of the dependence of intermittency exponents on the degree of compressibility, by
      a Lagrangian method for calculating simultaneous N-point tracer correlations.

PMID- 11969938
TI  - Statistical-mechanical study of the pair correlations for the dipolar Gay-Berne
      model.
AB  - A statistical-mechanical theory based upon the method of conditional distribution
      function has been applied to calculations of the nearest-neighbor (NN) and next
      NN correlators as well as order parameters. The method takes into account
      translational and orientational correlations as well as their coupling. Using the
      dipolar Gay-Berne interaction potential, calculations have been carried out for
      temperatures and densities corresponding to a nematic phase. The results in
      orientational distribution functions indicate a significant effect of the dipole
      dipole interactions on the orientational order of the liquid crystal. It was
      found that NN particles tend to be mutually antiparallel, whereas a reversed
      tendency is observed for next NN particles. These results are in agreement with
      computer simulations and with interpretations of experimental data.

PMID- 11969939
TI  - Fast relaxation of a hexagonal Poiseuille shear-induced near-surface phase in a
      threadlike micellar solution.
AB  - The dynamics of near-surface conformations in complex fluids under flow should
      dramatically affect their rheological properties. We have made the first
      measurements resolving the decay kinetics of a hexagonal phase induced in a
      threadlike polyionic micellar system under Poiseuille shear near a quartz
      surface. Upon cessation of shearing flow, this minimum interference crystalline
      phase formed within approximately 20 microm of the surface "melts" to a
      metastable two-dimensional liquid of aligned micelles in approximately 0.7 s.
      This is some three orders of magnitude shorter than the time required for bulk
      (Couette) shear-aligned micelles in this system to reach a fully entangled state.

PMID- 11969941
TI  - Coexistence of ordered and disordered phases in a nearly symmetric diblock
      copolymer near an order-disorder transition point.
AB  - We investigated the phase behavior near the order-disorder transition (ODT)
      temperature in a nearly symmetric diblock copolymer, using ultra-small-angle x
      ray scattering method. In a narrow temperature range very close to the ODT
      temperature, we observed the scattering profiles that can be interpreted as a
      linear combination of the scattering from the disordered state and that from the
      ordered lamellar state. These profiles were stable during the observation time
      (50 h), revealing that the two-phase coexistence occurs at thermal equilibrium
      within this temperature range.

PMID- 11969940
TI  - Phase separation with multiple length scales in polymer mixtures induced by
      autocatalytic reactions.
AB  - A ternary polymer blend with two components photo-cross-linked independently in
      its miscible region undergoes phase separation, exhibiting morphology with
      multiple length scales. Contrary to the case of thermally induced phase
      separation, the morphology exhibits a unimodal-->multimodal transition. It is
      shown that these multiple length scales are caused by the inhomogeneous freezing
      kinetics of the cross-linking process. This inhomogeneity arises from the
      autocatalytic feedback driven by the couplings between concentration fluctuations
      and the photo-cross-linking reactions.

PMID- 11969942
TI  - Periodicity-dependent stiffness of periodic hydrophilic-hydrophobic
      heteropolymers.
AB  - From extensive Monte Carlo simulations of a Larson model of perfectly periodic
      heteropolymers (PHP) in water, a striking stiffening is observed as the period of
      the alternating hydrophobic and hydrophilic blocks is shortened. At short period
      and low temperature needlelike conformations are the stable conformations. As
      temperature is increased thermal fluctuations induce kinks and bends. At large
      periods compact oligomeric globules are observed. From the generalized Larson
      prescription, originally developed for modeling surfactant molecules in aqueous
      solutions, we find that the shorter the period is the more stretched the PHP is.
      This novel effect is expected to stimulate polymer synthesis and trigger research
      on the rheology of aqueous periodic heteropolymer solutions.

PMID- 11969943
TI  - Numerical study of grid turbulence in two dimensions and comparison with
      experiments on turbulent soap films.
AB  - Numerical simulations of two dimensional channel flow behind an array of
      cylinders are carried out for high Reynolds numbers. Results for the energy
      density and enstrophy spectra, as well as for velocity and vorticity differences,
      are presented. The results compare favorably with recent experiments carried out
      with turbulent soap films. Some marked deviations from expected behavior are
      found for the enstrophy spectrum and for moments of vorticity increments.

PMID- 11969944
TI  - Direct measurement of the viscoelasticity of adsorbed protein layers using atomic
      force microscopy.
AB  - Thick layers of the protein lysozyme have been deposited on mica, and their force
      distance hysteresis measured using atomic force microscopy in the presence of
      different salts. Sodium thiocyanate, which is known to lower the melting
      temperature of proteins and increase their solubility, increases lysozyme
      deformability and lowers the viscosity of the protein layer, compared with sodium
      chloride. Sodium phosphate, known to raise the melting temperature and lower the
      solubility, decreases deformability and increases the viscosity.

PMID- 11969945
TI  - Suppression of transverse instabilities for vector solitons.
AB  - We analyze the transverse instability of two-component spatial solitons in a
      saturable nonlinear medium, in relation to recent experimental observations of
      spatial vector solitons in photorefractive media. We present the stability
      analysis for all three realizations: dark-bright, bright-bright, and dark-dark
      soliton pairs, and demonstrate that both the nonlinearity saturation and
      incoherent mode interaction can lead to a strong suppression of the soliton
      transverse instabilities.

PMID- 11969946
TI  - Tensile water transport in a porous gel.
AB  - A Monte Carlo simulation model, which incorporates the effect of tensile forces
      as well as diffusion, is proposed to explain the behavior of water transport in a
      saturated porous gel. The algorithm is able to account for the puzzling moisture
      profiles, which were first observed by conventional magnetic resonance imaging
      and, more recently, by Overhauser imaging.

PMID- 11969947
TI  - Efficient algorithm for calculating two-photon absorption spectra.
AB  - We propose an efficient time-dependent algorithm for nonlinear response function
      that requires CPU time proportional to the system size, and study the size
      effects in two-photon absorption spectra of Si nanocrystallites by using this
      algorithm.

PMID- 11969948
TI  - Simulations of fluid hydrogen: comparison of a dissociation model with tight
      binding molecular dynamics.
AB  - We compare the results of two complementary approaches, tight-binding molecular
      dynamics simulations and a dissociation model, for determining the
      characteristics of dense, fluid hydrogen at pressures extending to megabars and
      temperatures to 10 000 K. Two tight-binding models were examined: one
      parametrization emphasized crystalline, molecular, and fluid properties, the
      other focused more on the intricate molecular interactions involving up to four
      hydrogen atoms. The two tight-binding cases and the dissociation model agree
      reasonably well for a variety of properties, including the equation of state,
      dissociation degree, and proton pair-correlation functions. In simulations of
      recently reported laser-driven shock experiments, the tight-binding and
      dissociative models predict different maximum compressions of four and five,
      respectively. We discuss the sensitivities of the models as well as give
      estimates for the region of validity of the chemical picture (dissociation model)
      and the accuracy of the dynamical picture (tight-binding simulations) in cases
      where molecular hydrogen still dominates the physical behavior.

PMID- 11969949
TI  - Scaling properties of particle density fields formed in simulated turbulent
      flows.
AB  - Direct numerical simulations of particle concentrations in fully developed three
      dimensional turbulence were carried out in order to study the nonuniform
      structure of the particle density field. Three steady-state turbulent fluid
      fields with Taylor microscale Reynolds numbers (Re(lambda)) of 40, 80, and 140
      were generated by solving the Navier-Stokes equations with pseudospectral
      methods. Large-scale forcing was used to drive the turbulence and maintain
      temporal stationarity. The response of the particles to the fluid was
      parametrized by the particle Stokes number St, defined as the ratio of the
      particle's stopping time to the mean period of eddies on the Kolmogorov scale
      (eta). In this paper, we consider only passive particles optimally coupled to
      these eddies (St approximately 1) because of their tendency to concentrate more
      than particles with lesser or greater St values. The trajectories of up to
      70x10(6) particles were tracked in the equilibrated turbulent flows until the
      particle concentration field reached a statistically stationary state. The
      nonuniform structure of the concentration fields was characterized by the
      multifractal singularity spectrum f(alpha), derived from measures obtained after
      binning particles into cells ranging from 2eta to 15eta in size. We observed
      strong systematic variations of f(alpha) across this scale range in all three
      simulations and conclude that the particle concentration field is not
      statistically self-similar across the scale range explored. However, spectra
      obtained at the 2eta, 4eta, and 8eta scales of each flow case were found to be
      qualitatively similar. This result suggests that the local structure of the
      particle concentration field may be flow independent. The singularity spectra
      found for 2eta-sized cells were used to predict concentration distributions in
      good agreement with those obtained directly from the particle data. This
      singularity spectrum has a shape similar to the analogous spectrum derived for
      the inertial-range energy dissipation fields of experimental turbulent flows at
      Re(lambda)=110 and 1100. Based on this agreement, and the expectation that both
      dissipation and particle concentration are controlled by the same cascade
      process, we hypothesize that singularity spectra similar to the ones found in
      this work provide a good characterization of the spatially averaged statistical
      properties of preferentially concentrated particles in higher Re(lambda)
      turbulent flows.

PMID- 11969950
TI  - Mechanism of low-threshold hypersonic cavitation stimulated by broadband laser
      pump.
AB  - A low threshold acoustic cavitation regime was observed for the excitation of
      hypersonic waves due to a stimulated Brillouin scattering (SBS) mechanism, when
      the optical pump lies within the uv frequency range. Cavitation occurs if the
      optical pump bandwidth Delta(+)>>Omega(0), where Omega(0) is the Stokes frequency
      shift (the hypersonic frequency). In the opposite case (Delta(+)<<Omega(0)),
      cavitation does not occur despite the fact that the hypersonic wave intensity is
      much higher. The effect is associated with the stimulation of a broad frequency
      spectrum of hypersonic pressure in a field provided by the broadband optical
      pump. In contrast, for a monochromatic optical pump, the hypersonic wave is of
      single-frequency character. Induction of cavitation at the low intensities of
      acoustic pressure is attributed to nanobubbles of fixed size that occur in the
      liquid. The resonant frequency of the nanobubbles coincides with the frequency of
      some spectral component of hypersound present in the broadband SBS process. That
      conclusion is reinforced by the further observation that at the same intensity of
      broadband pumping the cavitation vanishes after degassing the liquid. In parallel
      experiments on four-photon polarization Rayleigh wing spectroscopy, it was also
      demonstrated that spectral lines exist in ordinary (not degassed) water, which
      can be ascribed to resonances of radial vibrations of nanobubbles. Those lines
      are absent in the degassed water spectrum.

PMID- 11969951
TI  - Planar isotropy of passive scalar turbulent mixing with a mean perpendicular
      gradient.
AB  - A recently proposed evolution equation [Vaienti et al., Physica D 85, 405 (1994)]
      for the probability density functions (PDF's) of turbulent passive scalar
      increments obtained under the assumptions of fully three-dimensional homogeneity
      and isotropy is submitted to validation using direct numerical simulation (DNS)
      results of the mixing of a passive scalar with a nonzero mean gradient by a
      homogeneous and isotropic turbulent velocity field. It is shown that this
      approach leads to a quantitatively correct balance between the different terms of
      the equation, in a plane perpendicular to the mean gradient, at small scales and
      at large Peclet number. A weaker assumption of homogeneity and isotropy
      restricted to the plane normal to the mean gradient is then considered to derive
      an equation describing the evolution of the PDF's as a function of the spatial
      scale and the scalar increments. A very good agreement between the theory and the
      DNS data is obtained at all scales. As a particular case of the theory, we derive
      a generalized form for the well-known Yaglom equation (the isotropic relation
      between the second-order moments for temperature increments and the third-order
      velocity-temperature mixed moments). This approach allows us to determine
      quantitatively how the integral scale properties influence the properties of
      mixing throughout the whole range of scales. In the simple configuration
      considered here, the PDF's of the scalar increments perpendicular to the mean
      gradient can be theoretically described once the sources of inhomogeneity and
      anisotropy at large scales are correctly taken into account.

PMID- 11969952
TI  - Possibility of breakdown of overdamped and narrowing limits in low-frequency
      Raman spectra: phenomenological band-shape analysis using the multiple-random
      telegraph model.
AB  - Depolarized low-frequency Raman spectra of liquid water and heavy water are
      investigated from 266 K to 356 K. The reduced Raman spectra below 250 cm(-1) are
      reproduced by a superposition of one relaxation mode and two damped harmonic
      oscillator modes. The multiple-random-telegraph (MRT) model, which takes into
      account inertia and memory effects, is applied to analyze the relaxation
      component. Two damped harmonic oscillators around 50 cm(-1) and 180 cm(-1) are
      known as a bendinglike mode and a stretchinglike mode, respectively. It is found
      that the intensity of the bendinglike mode in water (heavy water) gradually
      decreases with increasing temperature, and finally vanishes above about 296 K
      (306 K). The relaxation time of the MRT model is interpreted as representing the
      averaged lifetime of the vibrating unit. At high temperature, the relaxation time
      becomes short, that is to say, the vibrating unit is quickly destroyed before the
      50 cm(-1) mode is oscillating sufficiently. In the present analysis, the strongly
      disrupted oscillation cannot be distinguished from the relaxation mode which
      includes the inertia and memory effects. It is found that the low-frequency Raman
      spectrum of liquid water at high temperature is a good example demonstrating an
      application of the MRT model.

PMID- 11969953
TI  - Distribution functions of a simple fluid under shear: low shear rates.
AB  - Anisotropic pair distribution functions for a simple, soft sphere fluid at
      moderate and high density under shear have been calculated by nonequilibrium
      molecular dynamics, by equilibrium molecular dynamics with a nonequilibrium
      potential, and by a nonequilibrium distribution function theory [H. H. Gan and B.
      C. Eu, Phys. Rev. A 45, 3670 (1992)] and some variants. The nonequilibrium
      distribution function theory consists of a nonequilibrium Ornstein-Zernike
      relation, a closure relation, and a nonequilibrium potential and is solved in
      spherical harmonics. The distortion of the fluid structure due to shear is
      presented as the difference between the nonequilibrium and equilibrium pair
      distribution functions. From comparison of the results of theory against results
      of equilibrium molecular dynamics with the nonequilibrium potential at low shear
      rates, it is concluded that, for a given nonequilibrium potential, the theory is
      reasonably accurate, especially with the modified hypernetted chain closure. The
      equilibrium molecular-dynamics results with the nonequilibrium potential are also
      compared against the results of nonequilibrium molecular dynamics and suggest
      that the nonequilibrium potential used is not very accurate. In continuing work,
      a nonequilibrium potential better suited to high shear rates [H. H. Gan and B. C.
      Eu, Phys. Rev. A 46, 6344 (1992)] is being tested.

PMID- 11969954
TI  - Phase-field model for Hele-Shaw flows with arbitrary viscosity contrast. I.
      Theoretical approach.
AB  - We present a phase-field model for the dynamics of the interface between two
      inmiscible fluids with arbitrary viscosity contrast in a rectangular Hele-Shaw
      cell. With asymptotic matching techniques we check the model to yield the right
      Hele-Shaw equations in the sharp-interface limit, and compute the corrections to
      these equations to first order in the interface thickness. We also compute the
      effect of such corrections on the linear dispersion relation of the planar
      interface. We discuss in detail the conditions on the interface thickness to
      control the accuracy and convergence of the phase-field model to the limiting
      Hele-Shaw dynamics. In particular, the convergence appears to be slower for high
      viscosity contrasts.

PMID- 11969955
TI  - Phase-field model for Hele-Shaw flows with arbitrary viscosity contrast. II.
      Numerical study.
AB  - We implement a phase-field simulation of the dynamics of two fluids with
      arbitrary viscosity contrast in a rectangular Hele-Shaw cell. We demonstrate the
      use of this technique in different situations including the linear regime, the
      stationary Saffman-Taylor fingers, and the multifinger competition dynamics, for
      different viscosity contrasts. The method is quantitatively tested against
      analytical predictions and other numerical results. A detailed analysis of
      convergence to the sharp interface limit is performed for the linear dispersion
      results. We show that the method may be a useful alternative to more traditional
      methods.

PMID- 11969956
TI  - Time-modulated convection with zero mean temperature gradient.
AB  - We study numerically the onset of temporally modulated Rayleigh-Benard convection
      with zero mean gradient for cases of antisymmetric and asymmetric boundary
      temperatures over a continuous range of nondimensional frequencies omega, from
      omega approximately O(10(-1)) to omega approximately O(10(3)). For omega below 1,
      the neutral curves for Pr=7 in both cases alternate between synchronous and
      subharmonic responses, with increasingly shorter intervals as omega becomes
      small. At large omega, the critical wave number k(c) asymptotes to omega(1/2) and
      the critical Rayleigh number R(c) asymptotes to omega(3/2), via a subharmonic
      response in both cases. A comparison with the experimental results of Niemela and
      Donnelly [Phys. Rev. Lett. 57, 583 (1986)] shows fairly reasonable agreement.

PMID- 11969957
TI  - Stable elliptical vortices in a circular disk.
AB  - We show that large elliptical vortices in a finite disk are stable in a two
      dimensional (2D) ideal fluid (this also applies to a column of quasi-2D non
      neutral plasma in an axial magnetic field). The stability is established by
      comparison between the energy of elliptical and symmetrical states to satisfy a
      sufficient condition, without dynamical eigenanalysis. Analytical small
      ellipticity expansion of system energy and exact numerical values for arbitrary
      ellipticity are both obtained for uniform vortices. An approximating calculation
      is presented for general smooth vortices. Numerical simulations of the 2D Euler
      equation are also performed. The simulations not only confirm the sufficient
      condition, but also show that the stability persists to smaller vortex sizes. The
      reason why decaying l=2 modes were obtained by Briggs, Daugherty, and Levy [Phys.
      Fluids 13, 421 (1970)] using eigenanalysis is also discussed.

PMID- 11969958
TI  - Mechanism of single-bubble sonoluminescence.
AB  - The mechanism of the light emission of single-bubble sonoluminescence (SBSL) is
      studied theoretically based on the quasiadiabatic compression model. It is
      concluded that SBSL is not the blackbody radiation but the thermal radiation. It
      is clarified that the shape of the spectrum is determined by the temperature
      inside the bubble and the intensity is determined by the rates of the microscopic
      processes of the light emission. For a noble-gas bubble, radiative recombination
      of electrons and ions and electron-atom bremsstrahlung are the dominant
      microscopic processes of the light emission, and the intensity is mainly
      determined by the degree of ionization of the gas inside the bubble. It is also
      clarified that for a noble-gas bubble the pulse width of the light is nearly
      independent of wavelength.

PMID- 11969959
TI  - Effect of a magnetic field on sonoluminescence.
AB  - The effect of a magnetic field on single-bubble sonoluminescence in water
      reported experimentally by Young, Schmiedel, and Kang [Phys. Rev. Lett. 77, 4816
      (1996)] is studied theoretically. It is suggested that bubble dynamics is
      affected by the magnetic field because moving water molecules of the liquid
      suffer torque due to the Lorentz force acting on their electrical dipole moment,
      which results in the transformation of some of the kinetic energy into heat. It
      is shown that the magnetic field acts as if the ambient pressure of the liquid
      were increased. It is suggested that the effect increases as the amount of the
      liquid water increases. It is predicted that nonpolar liquid such as dodecane
      exhibits no effect of the magnetic field.

PMID- 11969960
TI  - Turbulent Dufour effect and Onsager-type relations.
AB  - In this paper we extend the work of Elperin et al. [Phys. Rev. Lett. 80, 69
      (1998)] by showing that a turbulent Dufour-type effect is also present in
      chemically nonreacting gaseous admixtures. This result is used to analyze the
      possibility of obtaining turbulent analogs of the Onsager relations, a
      fundamental result for molecular crossed effects in irreversible thermodynamics.

PMID- 11969961
TI  - Effect of lattice defects on Hele-Shaw flow over an etched lattice.
AB  - We examine the patterns formed by injecting nitrogen gas into the center of a
      horizontal, radial Hele-Shaw cell filled with paraffin oil. We use smooth plates
      and etched plates with lattices having different amounts of defects (0-10 %). In
      all cases, a quantitative measure of the pattern ramification shows a regular
      trend with injection rate and cell gap, such that the dimensionless perimeter
      scales with the dimensionless time. By adding defects to the lattice, we observe
      increased branching in the pattern morphologies. However, even in this case, the
      scaling behavior persists. Only the prefactor of the scaling function shows a
      dependence on the defect density. For different lattice defect densities, we
      examine the nature of the different morphology phases.

PMID- 11969962
TI  - Simple model for linear and nonlinear mixing at unstable fluid interfaces in
      spherical geometry.
AB  - A simple model was recently described for predicting linear and nonlinear mixing
      at an unstable planar fluid interface subjected to an arbitrary time-dependent
      variable acceleration history [J. D. Ramshaw, Phys. Rev. E 58, 5834 (1998)]. Here
      we present an analogous model for describing the mixing of two adjacent spherical
      fluid shells of different density resulting from an arbitrary time-dependent mean
      interface radius R(t). As in the planar case, the model is based on a heuristic
      expression for the kinetic energy of the system. This expression is based on that
      for the kinetic energy of a linearly perturbed interface, but with a dynamically
      renormalized effective wavelength which becomes proportional to the half-width
      a(t) of the mixing layer in the nonlinear regime. An equation of motion for
      s=R(2)a is then derived from Lagrange's equations. This evolution equation
      properly reduces to Plesset's equation for small perturbations, and to the
      previous planar model in the limit of very large R. The conservation properties
      of the model are established, and a suitable numerical scheme which preserves
      these properties is proposed.

PMID- 11969963
TI  - Subharmonic instabilities of Tollmien-Schlichting waves in two-dimensional
      Poiseuille flow.
AB  - The stability of the upper branch of shear traveling waves in two-dimensional
      Poiseuille flow, when the total flux through the channel is held constant, is
      considered. Taking into account the length of the periodic channel, perturbations
      of the same wave number (superharmonic), and different wave number (subharmonic)
      of the uniform wave trains are imposed. We mainly consider channels long enough
      to contain M=4 and M=8 basic wavelengths. In these cases, subharmonic
      bifurcations are found to be dominant except in a small region of parameters.
      From this type of bifurcation, we show that if the wave number is decreased, the
      periodic train of finite amplitude waves evolves continuously towards the stable
      localized wave packets obtained in long channels by other authors and whose
      existence has been associated to the vicinity of an inverted Hopf bifurcation.
      Depending on the basic wave number of the periodic train destabilized, different
      types of solutions for a given length of the channel can be obtained.
      Furthermore, for moderate Reynolds numbers, configurations of linearly stable
      wave trains exist, provided that their basic wave number is alpha approximately
      1.5.

PMID- 11969965
TI  - Twist modulated phases in chiral smectic liquid crystals.
AB  - By considering short period helical planar modulations about the layer normal, we
      construct a model free energy for the ferriclinic phases observed in chiral
      smectic liquid crystals. We then use this free energy to construct the phase
      diagram for our model. The resulting phases are compared with the experimentally
      observed smectic-C* subphases (ferroclinic, antiferroclinic, and heliclinic). A
      strong coupling is found between the ferroclinic q=2pi/a and the heliclinic
      q=2pi/3a modes. This coupling was not considered in previous models. The
      resulting additional stability of this "locked in" phase is discussed.

PMID- 11969964
TI  - Molecular reorientation of a nematic glass by laser-induced heat flow.
AB  - Laser-induced birefringence patterns which break the symmetry of the experimental
      setup have been observed in a low molar mass anisotropic glass with nematic
      orientational order under a polarizing microscope. It is shown that the observed
      spatial modulations in birefringence can be explained by laser-induced heat flow
      and stress, leading to molecular reorientation which is then frozen and stored in
      the glassy state if the optical excitation is switched off. The experimental
      findings can be regarded as a manifestation of heat-flow alignment caused by a
      spatially inhomogeneous temperature field.

PMID- 11969966
TI  - Pseudonematic order fluctuations of the director in the smectic phase of
      thermotropic liquid crystals.
AB  - The NMR spin-lattice proton relaxation dispersion in the smectic mesophase of two
      liquid crystals, 4cyano-4'-8-alkylbiphenyl and 4,4'-bis-heptyloxyazoxybenzene,
      are studied over several decades of Larmor frequencies. The results show that the
      order fluctuation of the local smectic director contribution to T1(nu(L))
      undergoes a transition between two power regimes: from T1(nu(L)) proportional,
      variantnu(1)(L) to nu(1/2)(L) on going from low to high Larmor frequencies. We
      explain this behavior by assuming, in the smectic mesophases, short coherence
      length nematiclike cooperative molecular reorientations.

PMID- 11969967
TI  - Kinetics of phase ordering of nematic liquid crystals confined in porous media.
AB  - Employing a time-dependent Ginzburg-Landau model, we investigate the influence of
      a random field on the phase ordering kinetics of nematic liquid crystals. We find
      that in the scaling regime the effect of random field (slowing down the growth of
      nematic) dominates over initial conditions for spatial dimensionality d< or =2,
      whereas for d>2 the random field has all its effect in the "initial-growth"
      regime. In this last case the mere confinement of liquid crystals is insufficient
      to produce slow growth of the nematic order.

PMID- 11969968
TI  - Time dependence of the magnetic grain concentration and secondary grain
      aggregation in ferronematic lyotropic liquid crystals subjected to magnetic field
      gradients.
AB  - The dynamical behavior of lyotropic nematic liquid crystals doped with ionic and
      surfacted magnetic fluids (ferronematics) is studied using a linear optical
      technique. The response of these mesophases to a combination of a static and a
      pulsed magnetic field is investigated by measuring the relaxation times as a
      function of the pulse width. A reversible modification of the magnetic grain
      concentration in the bulk of the samples and a secondary aggregation process due
      to the presence of a field gradient introduced by the pulsed field is discussed.

PMID- 11969969
TI  - Equilibrium structures and pretransitional fluctuations in a very thin hybrid
      nematic film.
AB  - The stability of different structures of a nematic liquid crystal in a planar
      hybrid film is examined within the framework of a Gaussian description of order
      fluctuations. In a very thin film the director field is not bent smoothly but
      exhibits a steplike change if the anchorings at the confining substrates are
      strong (G approximately > or =10(-3) J/m(2)) and comparable in magnitude. A
      (dis)continuous structural transition to the bent-director state which occurs
      with increasing film thickness or decreasing temperature is governed by the
      lowest bending director fluctuation mode. Its relaxation rate exhibits a critical
      slowdown when the film thickness approaches the "supercooling" limit or
      transition point, respectively. The (dis)continuity of the structural transition
      depends on the temperature and film thickness. The upper limit for the
      corresponding tricritical point is determined. The lowest order parameter mode,
      which corresponds to fluctuations of the position of the central exchange region,
      is characterized by a nearly critical behavior of the relaxation rate. The
      spectra of the two noncritical biaxial fluctuation modes are degenerate, whereas
      the fluctuation profiles are just mirror images with respect to the middle plane
      of the film.

PMID- 11969970
TI  - Magnetic field induced alignment of the directors of a smectic-A liquid crystal.
AB  - Deuterium NMR is used to monitor the magnetic field induced alignment of the
      directors in the smectic A phase of 4-octyl-4(')-cyanobiphenyl. The experiments
      consist of first preparing the sample as a monodomain by cooling slowly from the
      nematic phase in the magnetic field of the NMR spectrometer. The tube containing
      the sample is then rotated quickly through an angle theta(+), and the subsequent
      field induced alignment process followed by recording deuterium spectra over a
      period of time. The results obtained show that the magnetic field induced
      alignment of the directors in a smectic-A sample is qualitatively different from
      that of nematic samples. Results are reported for the pure mesogen containing
      deuteriums at the alpha chain position, and these are compared with data obtained
      on the alignment process by monitoring the deuterium spectrum of a small amount
      of an added solute, p-xylene-d(10).

PMID- 11969971
TI  - Improper orientational ordering regime and tricritical behavior in a lyotropic
      liquid crystal.
AB  - Optical microscopy, deuteron quadrupolar NMR, x-ray diffraction, and electrical
      conductivity techniques have been used to map the phase diagram and to measure
      the nematic order parameter variation (S) in ternary mixtures of
      pentadecafluorooctanoate acid ammonium salt (APFO), heavy water (D2O), and
      ammonium chloride (NH4Cl). A phenomenological model with an isotropic parent
      phase and a single primary segregation order parameter is elaborated on to
      describe in consistent terms the linear dependence of S(T) through the whole
      nematic stability region as well as the existence of a tricritical point at the
      nematic-to-lamellar phase transition line.

PMID- 11969972
TI  - Polydomain-monodomain transition in nematic elastomers.
AB  - Director textures and alignment of polydomain nematic elastomers under uniaxial
      extension are described theoretically applying the concept of randomly quenched
      disorder introduced by network cross-links. Within this model, treated with the
      replica trick and Gaussian variational approximation, the polydomain-monodomain
      transition occurs in a critical fashion with a small jump and rapid increase of
      the macroscopic order parameter. The transition is characterized by a plateau on
      the stress-strain curve. The critical stress value at which the transition takes
      place is estimated as approximately muQ(ch) with mu the rubber modulus of the
      elastomer and Q(ch) the parameter of chain anisotropy. The aligning of polydomain
      texture occurs via rotation of domains rather than their growth, with domain size
      almost unchanged through and above the transition. Experimental data obtained by
      several groups for various nematic elastomers are analyzed, showing a qualitative
      agreement with model predictions.

PMID- 11969973
TI  - Biaxial torus around nematic point defects.
AB  - We study the biaxial structure of both line and point defects in a nematic liquid
      crystal confined within a capillary tube whose lateral boundary enforces
      homeotropic anchoring. According to Landau-de Gennes theory the local order in
      the material is described by a second-order tensor Q, which encompasses both
      uniaxial and biaxial states. Our study is both analytical and numerical. We show
      that the core of a line defect with topological charge M=1 is uniaxial in the
      axial direction. At the lateral boundary, the uniaxial ordering along the radial
      direction is reached in two qualitatively different ways, depending on the sign
      of the order parameter on the axis. The point defects with charge M=+/-1 exhibit
      a uniaxial ring in the plane orthogonal to the cylinder axis. This ring is in
      turn surrounded by a torus on which the degree of biaxiality attains its maximum.
      The typical lengths that characterize the structure of these defects depend both
      on the cylinder radius and the biaxial correlation length. It seems that the core
      of the point defect does not depend on the far nematic director field in the bulk
      limit.

PMID- 11969974
TI  - Anticlinic coupling between layers of an antiferroelectric liquid crystal.
AB  - The anticlinic interlayer coupling coefficient U was evaluated as a function of
      temperature for a pitch-compensated liquid crystal by optical observation of the
      electric field-induced optic mode. U was found to exhibit an unusual "S-shaped"
      dependence on temperature, with values ranging between 0.4x10(4) and 2.2x10(4)
      erg cm(-3) over a 10 degrees C temperature range below the smectic-A-smectic
      C(*)(A) phase-transition temperature. The results are in good agreement with
      estimates for U based upon the threshold field for the onset of solitary waves,
      and provide strong support in the low-field regime for the single Fourier
      component model proposed by Li et al. [Phys. Rev. B 52, R13 075 (1995)].

PMID- 11969976
TI  - Expansion in width for domain walls in nematic liquid crystals in an external
      magnetic field.
AB  - The improved expansion in width is applied to curved domain walls in uniaxial
      nematic liquid crystals in an external magnetic field. In the present paper we
      concentrate on the case of equal elastic constants. We obtain an approximate form
      of the director field up to second order in the magnetic coherence length.

PMID- 11969975
TI  - Electromechanical Fredericks effects in nematic gels.
AB  - The solid nematic equivalent of the Fredericks transition is found to depend on a
      critical field rather than a critical voltage as in the classical case. This
      arises because director anchoring is principally to the solid rubbery matrix of
      the nematic gel rather than to the sample surfaces. Moreover, above the threshold
      field, we find a competition between quartic (soft) and conventional harmonic
      elasticity which dictates the director response. By including a small degree of
      initial director misorientation, the calculated field variation of optical
      anisotropy agrees well with the conoscopy measurements of Chang et al. [Phys.
      Rev. E 56, 595 (1997)] of the electro-optical response of nematic gels.

PMID- 11969977
TI  - Layer undulations induced by a magnetic or electric field in concentric
      cylindrical layers of smectic-A liquid crystals.
AB  - This paper derives theoretical results for the onset of Helfrich-Hurault-type
      transitions in samples of smectic-A liquid crystals arranged in concentric
      cylindrical layers [J. Chem. Phys. 55, 839 (1971); 59, 2068 (1973)]. A magnetic
      field is applied in the azimuthal direction, parallel to the layers. The
      governing equilibrium equation is solved in order to derive the critical
      magnitude H(c) of the magnetic field above which the onset of periodic smectic
      layer distortions is expected. The distortion solution is shown to be
      energetically favorable for H>H(c). Some examples of critical thresholds are
      given, by means of figures, for relevant physical parameters. The qualitative
      features of the solution at H(c) are displayed via the plot of a typical variable
      solution to the equilibrium equation in a particular case. The consequences of
      the results, especially the relationship between H(c) and the radial depth, are
      explored, and comparisons are drawn with known results for infinite planar
      aligned smectic-A samples. The results are also interpreted for the case of an
      electric field which follows the plane of the layers in the usual wedge geometry.
      Critical applied voltage magnitudes U(c) are derived for various radial sample
      depths and wedge angles.

PMID- 11969978
TI  - Spatiotemporal irregularity in an excitable medium with shear flow.
AB  - We consider an excitable medium moving with relative shear, subjected to a
      localized disturbance that in a stationary medium would produce a pair of spiral
      waves. The spiral waves so created are distorted and then broken by the motion of
      the medium. Such breaks generate new spiral waves, and so a "chain reaction" of
      spiral wave births and deaths is observed. This leads to a complicated
      spatiotemporal pattern, the "frazzle gas" [term suggested by Markus et al.,
      Nature (London) 371, 402 (1994)], which eventually fills the whole medium. In
      this paper, we display and interpret the main features of the pattern.

PMID- 11969979
TI  - Intrinsic instability of the concentration field in diffusion-limited growth and
      its effect on crystallization.
AB  - The dynamic behavior of the concentration field in crystallization is
      investigated by considering the coupling of the bulk concentration field and
      interfacial kinetics. It is shown that the concentration field may become
      unstable for perturbations with certain wavelength. When instability occurs, the
      physical environment in front of the growing interface will fluctuate and the
      interfacial growth mode will be affected accordingly. We suggest that our
      analysis can be used to interpret some spatial-temporal instabilities observed in
      crystallization.

PMID- 11969980
TI  - Microscopic basis of free-volume concept as studied by quasielastic neutron
      scattering and positron annihilation lifetime spectroscopy.
AB  - We have reexamined the free-volume concept presented by Cohen and Turnbull on the
      basis of two microscopic quantities: the excess mean-square displacement
      <u(2)>(f) and the total free volume V(PA,t), of poly- butadiene evaluated from
      the quasielastic neutron scattering and the positron annihilation lifetime
      spectroscopy (PALS) data, respectively. Comparing with the viscosity eta we found
      two relations, eta=eta(0) exp u( 2)(0)/<u(2)>(f) and eta=eta(0) exp
      V(*)(PA,0)/V(PA,t)=eta(0) exp V(*)(PA,0)/v(PA,f), where u(2)(0), V(*)(PA,0) and
      v(*)(PA,0) are the critical values for the mean-square displacement, the total
      PALS free volume, and the PALS free volume per molecule, respectively, and
      further v(*)(PA,0)=V(*)(PA,0)/N, N being the total number of molecules or
      segments. On the basis of these relations, we discuss the microscopic basis of
      the free-volume theory. The experimentally evaluated critical values u(2)(0) and
      v(*)(PA,0) are much larger than the average values of <u(2)>(f) and v(PA,f)
      calculated from the distributions. This has been explained from the low
      probability of escaping motions from a molecular cage. The free volume per
      monomer and the free-volume fraction were calculated from the excess mean-square
      displacement <u(2)>(f). The former was compared with the free-volume hole
      obtained by PALS, suggesting that 22 monomers are required for one PALS free
      volume hole. The free-volume fraction obtained from the excess mean-square
      displacement was found to be 6.4% at 250 K, which is in reasonable agreement with
      that evaluated from the rheological data (9.0%).

PMID- 11969981
TI  - Phase and solute fields across the solid-liquid interface of a binary alloy.
AB  - Solidification of binary alloys is characterized by a sharp structural transition
      across the solid-liquid interface. It is a typical situation which suggests a
      nonlocal dependence of the appropriate thermodynamic potential on its associate
      fields. Phase-field models with a gradient contribution for the order parameter
      have proved to account for nonequilibrium effects, as solute trapping and kinetic
      undercooling of the solid-liquid interface. The inclusion of a gradient term for
      the concentration field has also been theoretically investigated, but in this
      case the correspondence between predicted phenomena and experimental results is
      still rather unexplored. In the present study we analyze numerical solutions of a
      phase-field model in both steady and transient conditions. We focus on effects
      which are critically dependent on the composition field across the solid-liquid
      interface; the extent of the concentration gradient correction is related to
      measurable quantities to suggest methods for a comparison between the model
      predictions and experimental data.

PMID- 11969982
TI  - Intermolecular structure factors of macromolecules in solution: integral equation
      results.
AB  - The intermolecular structure of semidilute polymer solutions is studied
      theoretically. The low-density limit of a generalized Ornstein-Zernicke integral
      equation approach to polymeric liquids is considered. Scaling laws for the dilute
      to-semidilute crossover of the random-phase approximation (RPA)-like structure
      are derived for the intermolecular structure factor on large distances when
      intermolecular excluded volume is incorporated at the microscopic level. This
      leads to a nonlinear equation for the excluded volume interaction parameter. For
      macromolecular size-mass scaling exponents nu above a spatial-dimension dependent
      value, nu(c)=2/d, mean-field-like density scaling is recovered, but for nu<nu(c)
      the density scaling becomes nontrivial in agreement with field-theoretic results
      and justifying phenomenological extensions of the RPA. The structure of the
      polymer mesh in semidilute solutions is discussed in detail and comparisons with
      large-scale Monte Carlo simulations are added. Finally, a possibility to
      determine the correction to scaling exponent omega(12) is suggested.

PMID- 11969983
TI  - Polymerization-induced phase separation.
AB  - A molecular dynamics simulation is performed to study the kinetics of microphase
      separation in a polymer-dispersed-liquid-crystal forming process. An equimolar
      mixture of monomers and liquid crystal molecules are thermalized in a well mixed
      state. The monomers are then polymerized at the same temperature. The end product
      is a spanning gel with liquid crystal molecules aggregating in droplets here and
      there. The peak position of the equal-time structure function suggests that the
      growth of the droplets may be described with t(-0.23). The small growth exponent
      is just one of several features which may be attributed to the growing elastic
      gel. We argue that the aggregation is driven by entropy.

PMID- 11969984
TI  - Enhanced structural correlations accelerate diffusion in charge-stabilized
      colloidal suspensions.
AB  - Theoretical calculations for colloidal charge-stabilized suspensions and hard
      sphere suspensions show that hydrodynamic interactions yield a qualitatively
      different particle concentration dependence of the short-time self-diffusion
      coefficient. The effect, however, is numerically small and hardly accessible by
      conventional light-scattering experiments. By applying multiple-scattering
      decorrelation equipment and a careful data analysis we show that the theoretical
      prediction for charged particles is in agreement with our experimental results
      from aqueous polystyrene latex suspensions.

PMID- 11969985
TI  - Cracking piles of brittle grains.
AB  - A model which accounts for cracking avalanches in piles of grains subject to
      external load is introduced and numerically simulated. The stress is
      stochastically transferred from higher layers to lower ones. Cracked areas
      exhibit various morphologies, depending on the degree of randomness in the
      packing and on the ductility of the grains. The external force necessary to
      continue the cracking process is constant in a wide range of values of the
      fraction of already cracked grains. If the grains are very brittle, the force
      fluctuations become periodic in early stages of cracking. The distribution of
      cracking avalanches obeys a power law with exponent tau=2.4+/-0.1.

PMID- 11969986
TI  - Mechanism of the onset of axial segregation in a rotating cylindrical drum filled
      with binary granular mixtures.
AB  - A phenomenon of axial band formation in a long rotating cylindrical drum filled
      with a binary granular mixture is described as a two-stage process. At the first
      stage, due to different mobility of the large and small particles, a central core
      occupied by a small-size fraction is formed along the axis of the drum. The axial
      segregation, i.e., transverse band formation, is found to be associated with the
      instability of the radially segregated state caused by an asymmetry of the free
      surface of the granular material. This instability is caused by the difference in
      the repose angles of two granular fractions and deviation of the filling level of
      the drum from 0.5.

PMID- 11969987
TI  - Temperature scaling in a dense vibrofluidized granular material.
AB  - The leading order "temperature" of a dense two-dimensional granular material
      fluidized by external vibrations is determined. The grain interactions are
      characterized by inelastic collisions, but the coefficient of restitution is
      considered to be close to 1, so that the dissipation of energy during a collision
      is small compared to the average energy of a particle. An asymptotic solution is
      obtained where the particles are considered to be elastic in the leading
      approximation. The velocity distribution is a Maxwell-Boltzmann distribution in
      the leading approximation. The density profile is determined by solving the
      momentum balance equation in the vertical direction, where the relation between
      the pressure and density is provided by the virial equation of state. The
      temperature is determined by relating the source of energy due to the vibrating
      surface and the energy dissipation due to inelastic collisions. The predictions
      of the present analysis show good agreement with simulation results at higher
      densities where theories for a dilute vibrated granular material, with the
      pressure-density relation provided by the ideal gas law, are in error.

PMID- 11969988
TI  - Buckling, fluctuations, and collapse in semiflexible polyelectrolytes.
AB  - We present a systematic statistical mechanical analysis of the conformational
      properties of a stiff polyelectrolyte chain with intrachain attractions that are
      due to counterion correlations. We show that the mean-field solution corresponds
      to an Euler-like buckling instability. The effect of the conformational
      fluctuations on the buckling instability is investigated, first, qualitatively,
      within the harmonic ("semiclassical") theory, then, systematically, within a 1/d
      expansion, where d denotes the dimension of embedding space. Within the
      "semiclassical" approximation, we predict that the effect of fluctuations is to
      renormalize the effective persistence length to smaller values, but not to change
      the nature of the mean-field (i.e., buckling) behavior. Based on the 1/d
      expansion we are, however, led to conclude that thermal fluctuations are
      responsible for a change of the buckling behavior which is turned into a polymer
      collapse. A phase diagram is constructed in which a sequence of collapse
      transitions terminates at a buckling instability that occurs at a place that
      varies with the magnitude of the bare persistence length of the polymer chain, as
      well as with the strength and range of the attractive potential.

PMID- 11969989
TI  - Cylindrically symmetric Green's function approach for modeling the crystal growth
      morphology of ice.
AB  - We describe a front-tracking Green's function approach to modeling cylindrically
      symmetric crystal growth. This method is simple to implement, and with little
      computer power can adequately model a wide range of physical situations. We apply
      the method to modeling the hexagonal prism growth of ice crystals, which is
      governed primarily by diffusion along with anisotropic surface kinetic processes.
      From ice crystal growth observations in air, we derive measurements of the
      kinetic growth coefficients for the basal and prism faces as a function of
      temperature, for supersaturations near the water saturation level. These
      measurements are interpreted in the context of a model for the nucleation and
      growth of ice, in which the growth dynamics are dominated by the structure of a
      disordered layer on the ice surfaces.

PMID- 11969990
TI  - Continuum theory of axial segregation in a long rotating drum.
AB  - We develop a continuum description for the axial segregation of granular
      materials in a long rotating drum based on the dynamics of the thin near-surface
      granular flow coupled to bulk flow. The equations of motion are reduced to the
      one-dimensional system for two local variables only, the concentration difference
      and the dynamic angle of repose, or the average slope of the free surface. The
      parameters of the system are established from comparison with experimental data.
      The resulting system describes both initial transient traveling wave dynamics and
      the formation of quasi-stationary bands of segregated materials. A long-term
      evolution proceeds through slow logarithmic coarsening of the band structure
      which is analogous to the spinoidal decomposition described by the Cahn-Hilliard
      equation.

PMID- 11969991
TI  - Linear viscoelasticity of hard sphere colloidal crystals from resonance detected
      with dynamic light scattering.
AB  - We present measurements of the high-frequency shear modulus and dynamic viscosity
      for nonaqueous hard sphere colloidal crystals both in normal and microgravity
      environments. All experiments were performed on a multipurpose PHaSE instrument.
      For the rheological measurements, we detect the resonant response to oscillatory
      forcing with a dynamic light scattering scheme. The resonant response for
      colloidal crystals formed in normal and microgravity environments was similar,
      indicating that the bulk rheological properties are unaffected by differing
      crystal structure and crystallite size within the experimental error. Our high
      frequency shear modulus seems reasonable, lying close to Frenkel and Ladd's
      predictions [Phys. Rev. Lett. 59, 1169 (1987)] for the static modulus of hard
      sphere crystals. Our high-frequency dynamic viscosity, on the other hand, seems
      high, exceeding Shikata and Pearson [J. Rheol. 38, 601 (1994)] and van der Werff
      et al.'s measurements [Phys. Rev. A 39, 795 (1989)] on the high-frequency dynamic
      viscosity for metastable fluids. The measurements are in the linear regime for
      the shear modulus but may not be for the dynamic viscosity as Frith et al.
      [Powder Technol. 51, 27 (1987)] report that the dynamic viscosity passes through
      a maximum with strain amplitude.

PMID- 11969992
TI  - Force distribution in a scalar model for noncohesive granular material.
AB  - We study a scalar lattice model for intergrain forces in static, noncohesive,
      granular materials, obtaining two primary results: (i) The applied stress as a
      function of overall strain shows a power law dependence with a nontrivial
      exponent, which moreover varies with system geometry; and (ii) probability
      distributions for forces on individual grains appear Gaussian at all stages of
      compression, showing no evidence of exponential tails. With regard to both
      results, we identify correlations responsible for deviations from previously
      suggested theories.

PMID- 11969993
TI  - Thick surface flows of granular materials: effect of the velocity profile on the
      avalanche amplitude.
AB  - A few years ago, Bouchaud et al. introduced a phenomenological model to describe
      surface flows of granular materials [J. Phys. I 4, 1383 (1994)]. According to
      this model, one can distinguish between a static phase and a rolling phase that
      are able to exchange grains through an erosion or accretion mechanism. Boutreux
      et al. [Phys. Rev. E 58, 4692 (1998)] proposed a modification of the exchange
      term in order to describe thicker flows where saturation effects are present.
      However, these approaches assumed that the downhill convection velocity of the
      grains is constant inside the rolling phase, a hypothesis that is not verified
      experimentally. In this article, we therefore modify the above models by
      introducing a velocity profile in the flow, and study the physical consequences
      of this modification in the simple situation of an avalanche in an open cell. We
      present a complete analytical description of the avalanche in the case of a
      linear velocity profile, and generalize the results for a power-law dependency.
      We show, in particular, that the amplitude of the avalanche is strongly affected
      by the velocity profile.

PMID- 11969994
TI  - Convection and thermodiffusion of colloidal gold tracers by laser light
      scattering.
AB  - In a dynamic light scattering experiment, we have investigated the time intensity
      correlation function and the profile of the transmitted laser beam for organic
      dispersions of light absorbing colloidal particles containing tiny gold clusters.
      The correlation functions have been found to show a superposition of an
      exponential decay, corresponding to Brownian motion of the tracers, and well
      defined oscillations. These oscillations are caused by convection due to local
      heating of the sample by the incident laser beam, which has been confirmed
      independently via measurements of the local temperature within the sample. It
      will be shown how the particle convection velocity, which is the order of 1 mm/s,
      can be obtained quantitatively from the oscillating correlation functions. The
      profile of the transmitted beam allowed us to determine the Soret coefficient,
      which is a measure for the thermal diffusion of the particles. This article shows
      how tracer diffusion, convection, and thermal diffusion can be determined
      simultaneously by one single experiment, laser light scattering of light
      absorbing colloidal particles in dispersion.

PMID- 11969995
TI  - Auto-oscillation of surface tension.
AB  - Long-time auto-oscillation of the surface tension can evolve when in an aqueous
      system a diethyl phthalate droplet is placed under the free water surface. The
      experimental conditions for development of surface tension auto-oscillations are
      described. Based on a theoretical analysis the mechanism of these auto
      oscillations is proposed. The mechanism of the auto-oscillations results from a
      switching between diffusion and convection transfer of diethyl phthalate in the
      solution. A periodic Marangoni flow on the water surface resulting from a surface
      layer instability is discussed. The solubility of the amphiphile in the water and
      its surface activity are the main characteristics that determine the system
      behavior.

PMID- 11969996
TI  - Diffusiophoresis of two-dimensional liquid droplets in a phase-separating system.
AB  - The motion of phase-separating liquid drops was simulated in two dimensions
      following the model H, where convection and diffusion are coupled via a body
      force, expressing the tendency of demixing systems to minimize their free energy.
      This driving force depends on the capillary number, i.e., the ratio of viscous to
      thermal forces, which in a typical case is of order 10(-4), inducing a convective
      material flux much larger than its diffusive counterpart. Three problems were
      considered. In the first, we studied the motion of a single drop immersed in a
      continuum field with constant concentration gradient, finding that the drop speed
      is proportional to the concentration gradient and inversely proportional to the
      capillary number. In the second problem, we found that the motion of a single
      drop immersed in a homogeneous concentration field depends on the difference
      (Delta(phi))(0) between the initial concentration of the continuum phase and its
      equilibrium value. In fact, when (Delta(phi))(0)<0, the drop shrinks without
      moving, while when (Delta(phi))(0)>0, the drop consumes material from the
      surrounding field and moves randomly, propelled by the induced capillary driving
      force. During its movement, the drop grows linearly in time, with a growth rate
      proportional to the ratio between molecular diffusivity and interface thickness.
      In addition, during its random motion, the drop mean square displacement grows
      linearly with time, with an effective diffusion coefficient which is of the same
      magnitude as the molecular diffusivity. The predicted drop growth rate and mean
      velocity are in good agreement with experimental observations. Finally, the
      motion of two drops is studied, showing that the capillary forces induce a mutual
      attraction between the two drops. When (Delta(phi))(0)<0, the attractive force is
      unchallenged, thus leading always to coalescence, while when (Delta(phi))(0)>0 a
      screening effect arises which may keep the two drops apart from each other.

PMID- 11969997
TI  - Vertical free-standing films of amphiphilic associating polyelectrolytes.
AB  - Hydrophobically modified poly(acrylic acid) sodium salt (HMPAANa) copolymers are
      known to provide a huge stabilization of oil in water macroemulsions. An
      interstitial HMPAANa film is formed between the oil droplets, thus creating
      repulsion between them. We present an x-ray reflectivity study of vertical free
      standing films drawn from aqueous solutions of HMPAANa copolymers. The vertical
      HMPAANa films are model systems for the interstitial films between oil droplets
      and the description of their behavior provides information about the
      stabilization process. Their thickness was investigated as a function of various
      parameters such as the solution concentration, the degree of grafting, the length
      of the grafts, and the backbone molecular weight. Below a solution concentration
      threshold (C(t)), the film thickness scales like the square root of the molecular
      weight and is independent of the degree of grafting and the length of the grafts.
      Polyelectrolyte chains adopt a self-screened coil conformation within the films
      and the thickness is governed by the radius of gyration of the coils. Above C(t),
      a transition from a bimolecular film to a physical gel is observed and the
      thickness then increases with concentration. Finally, we propose an explanation
      for the stabilization of macroemulsions by HMPAANa copolymers.

PMID- 11969998
TI  - Simulations of aerosol aggregation including long-range interactions.
AB  - Current understanding of solid aerosol particle aggregation is limited to
      simulation models based on diffusive and ballistic motion of the colliding
      particles. The role of the long-range van der Waals forces in aggregation
      phenomena, although important, has never been examined. In an effort to address
      this issue, a simulation model, based on molecular dynamics techniques, is
      developed. Using this model to simulate thermal collisions of single spheres with
      small aggregates of similar spheres, we examine the effects of retardation of the
      long-range van der Waals forces, particle transport, ambient temperature, and
      pressure on the collision rates and mass and structure distributions of the
      aggregated particles. The model calculations were performed at simulated
      temperatures of 293 and 1500 K and at simulated pressures of 760 and 3040 torr
      for glassy carbon primary particles in the free molecular regime with diameters
      of 6 nm, and in the transition regime with diameters of 30 nm. Inclusion of the
      long-range van der Waals forces resulted in aggregates with relatively open
      structures and few branches and collision rate constants that were larger than
      the corresponding hard sphere rate constants, whereas exclusion of the forces
      resulted in compact structures with more branches and smaller enhancements in the
      rate constants. The above effects were found to be more pronounced in the free
      molecular regime than in the transition regime, which is consistent with the
      observation that the initial conditions and the interparticle forces play a more
      significant role in particle transport in the free molecular regime than in the
      transition regime. The effect of retardation of the forces is an increase in the
      percentage of open aggregates and the collision rate constants over that of the
      corresponding nonretarded case. An increase in temperature resulted in a collapse
      of aggregate structure and a decrease in collision rate constants corresponding
      to the reduced geometrical cross sections. Again, the effects were found to be
      more pronounced in the free molecular regime than in the transition regime. No
      significant difference was observed in the structure of the aggregates or in the
      collision rate constants with a change in pressure, indicating that the pressure
      effect, if any, is hidden by the much stronger effect of the long-range van der
      Waals forces.

PMID- 11969999
TI  - Configurational entropy and collective modes in normal and supercooled liquids.
AB  - Soft vibrational modes have been used to explain anomalous thermal properties of
      glasses above 1 K. The soft-potential model consists of a collection of double
      well potentials that are distorted by a linear term representing local stress in
      the liquid. Double-well modes contribute to the configurational entropy of the
      system. Based on the Adam-Gibbs theory of entropically driven relaxation in
      liquids, we show that the presence of stress drives the transition from Arrhenius
      to Zwanzig-Bassler temperature dependence of relaxation times. At some
      temperature below the glass transition, the energy scale is dominated by local
      stress, and soft modes are described by single wells only. It follows that the
      configurational entropy vanishes, in agreement with the "Kauzmann paradox." We
      discuss a possible connection between soft vibrational modes and ultrafast
      processes that dominate liquid dynamics near the glass transition.

PMID- 11970000
TI  - Theta-point behavior of diluted polymer solutions: can one observe the universal
      logarithmic corrections predicted by field theory?
AB  - In recent large-scale Monte Carlo simulations of various models of Theta-point
      polymers in three dimensions Grassberger and Hegger found logarithmic corrections
      to mean field theory with amplitudes much larger than the universal amplitudes of
      the leading logarithmic corrections calculated by Duplantier in the framework of
      tricritical O(n) field theory. To resolve this issue we calculate the universal
      subleading correction of field theory, which turns out to be of the same order of
      magnitude as the leading correction for all chain lengths available in present
      day simulations. Borel resummation of the renormalization group flow equations
      also shows the presence of such large corrections. This suggests that the
      published simulations did not reach the asymptotic regime. To further support
      this view, we present results of Monte Carlo simulations on a Domb-Joyce-like
      model of weakly interacting random walks. Again the results cannot be explained
      by keeping only the leading corrections, but are in fair accordance with our full
      theoretical result. The corrections found for the Domb-Joyce model are much
      smaller than those for other models, which clearly shows that the effective
      corrections of are not yet in the asymptotic regime. Altogether, our findings
      show that the existing simulations of Theta polymers are compatible with
      tricritical field theory, since the crossover to the asymptotic regime is very
      slow. Similar results were found earlier for self-avoiding walks at their upper
      critical dimension d(c)=4.

PMID- 11970001
TI  - Mode locking and Arnold tongues in integrate-and-fire neural oscillators.
AB  - An analysis of mode-locked solutions that may arise in periodically forced
      integrate-and-fire (IF) neural oscillators is introduced based upon a firing map
      formulation of the dynamics. A q:p mode-locked solution is identified with a
      spike train in which p firing events occur in a period qDelta, where Delta is the
      forcing period. A linear stability analysis of the map of firing times around
      such solutions allows the determination of the Arnold tongue structure for
      regions in parameter space where stable solutions exist. The analysis is verified
      against direct numerical simulations for both a sinusoidally forced IF system and
      one in which a periodic sequence of spikes is used to induce a biologically
      realistic synaptic input current. This approach is extended to the case of two
      synaptically coupled IF oscillators, showing that mode-locked states can exist
      for some self-consistently determined common period of repetitive firing.
      Numerical simulations show that such solutions have a bursting structure where
      regions of spiking activity are interspersed with quiescent periods before
      repeating. The influence of the synaptic current upon the Arnold tongue structure
      is explored in the regime of weak coupling.

PMID- 11970002
TI  - Correlations between hidden units in multilayer neural networks and replica
      symmetry breaking.
AB  - We consider feed-forward neural networks with one hidden layer, tree
      architecture, and a fixed hidden-to-output Boolean function. Focusing on the
      saturation limit of the storage problem the influence of replica symmetry
      breaking on the distribution of local fields at the hidden units is investigated.
      These field distributions determine the probability of finding a specific
      activation pattern of the hidden units as well as the corresponding correlation
      coefficients and therefore quantify the division of labor among the hidden units.
      We find that although modifying the storage capacity and the distribution of
      local fields markedly replica symmetry breaking has only a minor effect on the
      correlation coefficients. Detailed numerical results are provided for the PARITY,
      COMMITTEE, and AND machines with K=3 hidden units and nonoverlapping receptive
      fields.

PMID- 11970003
TI  - Discretized torsional dynamics and the folding of an RNA chain.
AB  - The aim of this work is to implement a discrete coarse codification of local
      torsional states of the RNA chain backbone in order to explore the long-time
      limit dynamics and ultimately obtain a coarse solution to the RNA folding
      problem. A discrete representation of the soft-mode dynamics is turned into an
      algorithm for a rough structure prediction. The algorithm itself is inherently
      parallel, as it evaluates concurrent folding possibilities by pattern
      recognition, but it may be implemented in a personal computer as a chain of
      perturbation-translation-renormalization cycles performed on a binary matrix of
      local topological constraints. This requires suitable representational tools and
      a periodic quenching of the dynamics for system renormalization. A binary coding
      of local topological constraints associated with each structural motif is
      introduced, with each local topological constraint corresponding to a local
      torsional state. This treatment enables us to adopt a computation time step far
      larger than hydrodynamic drag time scales. Accordingly, the solvent is no longer
      treated as a hydrodynamic drag medium. Instead we incorporate its capacity for
      forming local conformation-dependent dielectric domains. Each translation of the
      matrix of local topological constraints (LTM's) depends on the conformation
      dependent local dielectric created by a confined solvent. Folding pathways are
      resolved as transitions between patterns of locally encoded structural signals
      which change within the 1 ns-100 ms time scale range. These coarse folding
      pathways are generated by a search at regular intervals for structural patterns
      in the LTM. Each pattern is recorded as a base-pairing pattern (BPP) matrix, a
      consensus-evaluation operation subject to a renormalization feedback loop. Since
      several mutually conflicting consensus evaluations might occur at a given time,
      the need arises for a probabilistic approach appropriate for an ensemble of RNA
      molecules. Thus, a statistical dynamics of consensus formation is determined by
      the time evolution of the base pairing probability matrix. These dynamics are
      generated for a functional RNA molecule, a representative of the so-called group
      I ribozymes, in order to test the model. The resulting ensemble of conformations
      is sharply peaked and the most probable structure features the predominance of
      all phylogenetically conserved intrachain helices tantamount to ribozyme
      function. Furthermore, the magnesium-aided cooperativity that leads to the
      shaping of the catalytic core is elucidated. Once the predictive folding
      algorithm has been implemented, the validity of the so-called "adiabatic
      approximation" is tested. This approximation requires that conformational
      microstates be lumped up into BPP's which are treated as quasiequilibrium states,
      while folding pathways are coarsely represented as sequences of BPP transitions.
      To test the validity of this adiabatic ansatz, a computation of the coarse
      Shannon information entropy sigma associated to the specific partition of
      conformation space into BPP's is performed taking into account the LTM evolution
      and contrasted with the adiabatic computation. The results reveal a subordination
      of torsional microstate dynamics to BPP transitions within time scales relevant
      to folding. This adiabatic entrainment in the long-time limit is thus identified
      as responsible for the expediency of the folding process.

PMID- 11970004
TI  - Dynamic feedback in an aggregation-disaggregation model.
AB  - We study an aggregation-disaggregation model which is relevant to biological
      processes such as the growth of senile plaques in Alzheimer disease. In this
      model, during the aggregation each deposited particle has a probability of
      producing a new particle in its vicinity, while during disaggregation the
      particles are anihilated randomly. The model is held in a dynamic equilibrium by
      a feedback mechanism which changes the disaggregation probability in proportion
      to the change in the total number of particles. We also include surface diffusion
      which influences the morphology of growing aggregates and colonies. A colony
      includes the descendents of a single particle. We investigate the statistical
      properties of the model in two dimensions. We find that unlike the colonies,
      individual aggregates are fractals with a fractal dimension of D(f)=1.92+/-0.06
      in the absence of surface diffusion. We show that the surface diffusion changes
      the fractal dimension of aggregates: at a small aggregation-disaggregation rate,
      D(f) is independent of the strength of the surface diffusion, D(f)=1.73+/-0.03.
      At larger aggregation-disaggregation rates and different strengths of surface
      diffusion, aggregates with fractal dimensions between D(f)=1.73 and 1.92 form.
      The steady-state distribution of aggregate sizes is shown to be power law if the
      aggregation-disaggregation process dominates over the surface diffusion. In the
      limit of weak aggregation-disaggregation and strong surface diffusion the size
      distribution is log-normal.

PMID- 11970005
TI  - Energy transduction of isothermal ratchets: generic aspects and specific examples
      close to and far from equilibrium.
AB  - We study the energetics of isothermal ratchets which are driven by a chemical
      reaction between two states, and operate in contact with a single heat bath of
      constant temperature. We discuss generic aspects of energy transduction such as
      Onsager relations in the linear response regime as well as the efficiency and
      dissipation close to and far from equilibrium. In the linear response regime
      where the system operates reversibly, the efficiency is in general nonzero.
      Studying the properties for specific examples of energy landscapes and
      transitions, we observe in the linear response regime that the efficiency can
      have a maximum as a function of temperature. Far from equilibrium in the fully
      irreversible regime, we find a maximum of the efficiency with values larger than
      in the linear regime for an optimal choice of the chemical driving force. We show
      that the corresponding efficiencies can be of the order of 50%. A simple analytic
      argument allows us to estimate the efficiency in this irreversible regime for
      small external forces.

PMID- 11970006
TI  - Information theoretical performance measure for associative memories and its
      application to neural networks.
AB  - We present a general performance measure (information loss) for associative
      memories based on information theoretical concepts. This performance measure can
      be estimated, provided that mean values of observables have been determined for
      the associative memory. Then the estimation guarantees a minimal association
      quality. The formalism allows the application of the performance measure to
      complex systems where the relation between input and output of the associative
      memory is not explicitly known. Here we apply our formalism to the Hopfield model
      and estimate the storage capacity alpha(c) from the numerically determined
      information loss. In contrast to other numerical methods the whole overlap
      distribution is taken into account. Our numerical value alpha(c)=0.1379(4) for
      the storage capacity in the Hopfield model is below numerical values obtained
      previously. This indicates that the consideration of small remnant overlaps
      lowers the storage capacity of the Hopfield model.

PMID- 11970007
TI  - Polyion character of globular proteins detected by translational and rotational
      diffusion.
AB  - Photon correlation spectroscopy measurements are performed on a solution of
      lysozyme, a small, highly charged protein at pH=4, in glycerol-buffer mixtures.
      From the correlation functions of the polarized and depolarized scattered
      intensity, we derive an effective protein radius by inverting the Stokes Einstein
      relation for either the translational or the rotational diffusion, as a function
      of the protein concentration 0< or =C< or =40 g/L. The translational radius
      decreases with the protein concentration and extrapolates at C approximately 0 to
      a value slightly larger than the mean rotational radius, which is independent of
      the protein concentration. By employing recent calculations on electrolyte
      friction effects (eletrolyte-protein interactions) on both the translational and
      rotational radius and by keeping also into account the protein-protein
      electrostatic interactions, we are able to account for the observed differences,
      suggesting also that lysozyme is more highly hydrated in glycerol mixtures than
      in the pure buffer. These results indicate that depolarized photon correlation
      spectroscopy measurements can be used as a valuable tool to detect small changes
      in the overall protein size.

PMID- 11970008
TI  - Adaptive walks on time-dependent fitness landscapes.
AB  - The idea of adaptive walks on fitness landscapes as a means of studying
      evolutionary processes on large time scales is extended to fitness landscapes
      that are slowly changing over time. The influence of ruggedness and of the amount
      of static fitness contributions is investigated for model landscapes derived from
      Kauffman's NK landscapes. Depending on the amount of static fitness contributions
      in the landscape, the evolutionary dynamics can be divided into a percolating and
      a nonpercolating phase. In the percolating phase, the walker performs a random
      walk over the regions of the landscape with high fitness.

PMID- 11970009
TI  - Mean-field theory of globally coupled integrate-and-fire neural oscillators with
      dynamic synapses.
AB  - We analyze the effects of synaptic depression or facilitation on the existence
      and stability of the splay or asynchronous state in a population of all-to-all,
      pulse-coupled neural oscillators. We use mean-field techniques to derive
      conditions for the local stability of the splay state and determine how stability
      depends on the degree of synaptic depression or facilitation. We also consider
      the effects of noise. Extensions of the mean-field results to finite networks are
      developed in terms of the nonlinear firing time map.

PMID- 11970011
TI  - Multistability analysis of phase locking patterns in an excitatory coupled neural
      system.
AB  - We quantitatively analyze the multistability of dynamic patterns of a bursting
      neural system with diffusive coupling. Through effective coupling analysis, we
      show that the system is not in-phase locking but exhibits various phase locking
      patterns, each of which corresponds to the stable fixed points of the effective
      coupling. The simulation proves the validity of the effective coupling method in
      analyzing the multistability of neural systems which presents complicated dynamic
      patterns such as bursting.

PMID- 11970010
TI  - Electrical recordings from rat cardiac muscle cells using field-effect
      transistors.
AB  - Extracellular electrophysiological recordings were made from cardiac cells
      cultured for up to seven days over microfabricated arrays of field-effect
      transistors. The recorded signals can be separated mainly into two types of cell
      transistor couplings: one that can be explained entirely by purely passive
      circuitry elements, and a second where voltage-gated ion channels contribute
      greatly to the measured extracellular signal.

PMID- 11970012
TI  - Response of coupled noisy excitable systems to weak stimulation.
AB  - It is known that coupling can enhance the response of noisy bistable devices to
      weak periodic modulation. This work examines whether a similar phenomenon occurs
      in the active rotator model for excitable systems. We study the dynamics of
      assemblies of weakly periodically modulated active rotators. The addition of
      noise to these brings about a number of behaviors that have no counterpart in
      networks of bistable systems. The analysis of the dynamics of the solution of the
      Fokker-Planck equation of active rotator networks shows that these new behaviors
      are similar to generic responses of periodically forced autonomous oscillators.
      This is because noise alone, in the absence of other inputs, can regularize the
      dynamics of single active rotators through coherence resonance, and lead to
      regular synchronous activity at the level of networks. We argue that similar
      phenomena take place in a broad class of excitable systems.

PMID- 11970013
TI  - Chaos in neural networks with a nonmonotonic transfer function.
AB  - Time evolution of diluted neural networks with a nonmonotonic transfer function
      is analytically described by flow equations for macroscopic variables. The
      macroscopic dynamics shows a rich variety of behaviors: fixed-point, periodicity,
      and chaos. We examine in detail the structure of the strange attractor and in
      particular we study the main features of the stable and unstable manifolds, the
      hyperbolicity of the attractor, and the existence of homoclinic intersections. We
      also discuss the problem of the robustness of the chaos and we prove that in the
      present model chaotic behavior is fragile (chaotic regions are densely
      intercalated with periodicity windows), according to a recently discussed
      conjecture. Finally we perform an analysis of the microscopic behavior and in
      particular we examine the occurrence of damage spreading by studying the time
      evolution of two almost identical initial configurations. We show that for any
      choice of the parameters the two initial states remain microscopically distinct.

PMID- 11970014
TI  - Partially ionized hydrogen plasma in strong magnetic fields.
AB  - We study the thermodynamic properties of a partially ionized hydrogen plasma in
      strong magnetic fields, B approximately 10(12)-10(13) G, typical of neutron
      stars. The properties of the plasma depend significantly on the quantum
      mechanical sizes and binding energies of the atoms, which are strongly modified
      by thermal motion across the field. We use new fitting formulas for the atomic
      binding energies and sizes, based on accurate numerical calculations and valid
      for any state of motion of the atom. In particular, we take into account
      decentered atomic states, neglected in previous studies of thermodynamics of
      magnetized plasmas. We also employ analytic fits for the thermodynamic functions
      of nonideal fully ionized electron-ion Coulomb plasmas. This enables us to
      construct an analytic model of the free energy. An ionization equilibrium
      equation is derived, taking into account the strong magnetic field effects and
      the nonideality effects. This equation is solved by an iteration technique.
      Ionization degrees, occupancies, and the equation of state are calculated.

PMID- 11970015
TI  - Comparison of measured and calculated X-ray and hot-electron production in short
      pulse laser-solid interactions at moderate intensities.
AB  - Ultrashort pulse laser-solid interaction experiments with 4x10(16) W/cm(2),120
      fs, 45 degrees incidence angle, p-polarized pulses are theoretically analyzed
      with the help of 1(1/2)-dimensional (1(1/2) D) particle-in-cell (PIC)
      simulations. The laser impinges upon preformed plasmas with a precisely
      controlled density-gradient scale-length. PIC electron distribution functions are
      used as an input to 3D Monte Carlo simulations to interpret measured electron
      distributions and Kalpha radiation emission. Satisfactory agreement between the
      experimental and simulation results is obtained for the measured absorption
      coefficient, the energy distribution of the back-scattered hot electrons, the hot
      electron temperature in the bulk of the target, and the Kalpha yield, when the
      preplasma scale-length is varied.

PMID- 11970016
TI  - Generation of periodic accelerating structures in plasma by colliding laser
      pulses.
AB  - A mechanism for generating large (>1 GeV/m) accelerating wakes in a plasma is
      proposed. Two slightly detuned counterpropagating laser beams, an ultrashort
      timing pulse and a long pump, exchange photons and deposit the recoil momentum in
      plasma electrons. This produces a localized region of electron current, which
      acts as a virtual electron beam, inducing intense plasma wakes with phase
      velocity equal to the group velocity of the short pulse. Modulating the pumping
      beam generates periodic accelerating structures in the plasma ("plasma linac")
      which can be used for particle acceleration unlimited by the dephasing between
      the particles and the wake. An important difference between this type of plasma
      accelerator and the conventional wakefield accelerators is that this type can be
      achieved with laser intensities I<<10(18) W/cm(2).

PMID- 11970017
TI  - Effect of excited states on the ionization balance in plasmas via the enhancement
      of ionization and recombination rate coefficients.
AB  - The effect of excited states on the effective ionization and recombination rate
      coefficients for the ground states was investigated analytically and by computer
      simulation. The calculation was done for carbon ions. The results using carbon
      ions show (1) the contribution from excited states to ionization rate
      coefficients becomes significant even at an electron density as low as 10(15) cm(
      3) and saturated from around N(e) approximately 10(20) cm(-3); (2) the lower the
      electron temperature, the larger the contribution; (3) in the case of
      recombination rate coefficients, there is still a non-negligible contribution
      from excited states even at a very low electron density of 10(10) cm(-3), where
      the contribution has been considered negligible; (4) this contribution to the
      recombination rate coefficients increases linearly with the electron density; (5)
      the enhancements of the ionization and recombination rate coefficients increase
      as N(e) increases and are saturated to the same value at higher densities; (6)
      there exists a region of temperature and density where the recombination is
      effectively hindered. Some of the behaviors of the ionization and recombination
      rate coefficients in the extreme regions of a very low and high electron density
      were analytically understood. The calculated ionization and recombination rate
      coefficients for carbon ions, including the effect of excited states, were used
      in a one-dimensional magnetohydrodynamic code for the calculation of the
      ionization balance of carbon ions in a Z-pinch carbon plasma and the gain of C VI
      H(alpha) (18.2 nm) line. The significant change in the evolution of the
      ionization balance was observed. The rapid depletion of C VII ions by the
      increased recombination rate reduces the gain significantly by a factor of
      approximately 3 compared to the case where the contribution from excited states
      was neglected. Such calculations can be done for other ions. The characteristics
      found for carbon ions are generic and applicable to other ions.

PMID- 11970019
TI  - Formation mechanisms of radial electron fluxes in a positive column.
AB  - The main physical formation mechanisms of differential radial electron fluxes
      (i.e., of the fluxes which correspond to different parts of the distribution
      function) in a dc positive column are discussed. It is shown that the magnitude
      and even sign of these fluxes depend crucially on whether the electron
      distribution is local or nonlocal and on electron energy. In the case of a
      nonlocal electron distribution the flux of slow electrons in the body of the
      distribution function is directed outward (to the wall), and for the fast
      electrons both directions are possible. The flux directed outward results from
      escape of the electrons to the tube wall, and the flux directed inward is caused
      by inelastic collision with large energy losses. In the local case the flux of
      the fast electrons, with the exception of a small wall vicinity, is directed
      inward, and the fluxes of the electrons in the distribution body are directed
      both inward and outward depending on the energy relaxation law.

PMID- 11970018
TI  - Charged-particle transport in gases in electric and magnetic fields crossed at
      arbitrary angles: Multiterm solution of Boltzmann's equation.
AB  - A multiterm solution of the Boltzmann equation has been developed and used to
      calculate transport coefficients of charged-particle swarms in gases under the
      influence of electric and magnetic fields crossed at arbitrary angles psi. The
      hierarchy resulting from a spherical harmonic decomposition of the Boltzmann
      equation in the hydrodynamic regime [Ness, Phys. Rev. A 47, 327 (1993)] is solved
      numerically by representing the speed dependence of the phase-space distribution
      function in terms of an expansion in Sonine polynomials about a weighted sum of
      Maxwellian distributions at different temperatures. Results are given for charged
      particle swarms in certain model gases over a range of psi and field strengths.
      The variation of the transport coefficients with psi is addressed using physical
      arguments. The errors associated with the two-term approximation and inadequacies
      of Legendre polynomial expansions are highlighted.

PMID- 11970021
TI  - Wiggler-field effects on the space-charge waves of a Raman free-electron laser.
AB  - An analysis of the propagation of a space-charge wave through the wiggler and
      axial magnetic fields of a free-electron laser is presented. The relativistic
      electron beam is contained within and only partially fills a cylindrical metallic
      waveguide. A theory is developed using lab-frame Maxwell and fluid equations in a
      form which is equivalent to the electrostatic approximation in the beam frame.
      The computational method of determining the dispersion relation is described and
      some numerical results are presented which illustrate effects arising from the
      wiggler and the partially filled waveguide.

PMID- 11970020
TI  - Coulomb logarithm in femtosecond-laser-matter interaction.
AB  - In femtosecond-laser-matter interaction, collisional absorption plays an
      important role during the early stages of the interaction, when the laser
      intensity and the plasma temperature still have moderate values. We propose a
      cutoff impact parameter b(max) for the Coulomb logarithm lambda=ln Lambda in the
      electron-ion collision rate which takes into account, for an overdense plasma,
      the crystalline structure of the ion background. Calculations are presented for a
      bcc lattice and generalized to sc and fcc lattices. The results are applicable
      for laser intensities I(l)< or =10(17) W cm(-2) and when the Debye theory is
      valid, that is to say, when the Landau length is distinctly less than the minimum
      ion distance, and when the Debye screening is unaffected by the electron quiver
      motion in the laser field. We present the space angle dependence of the cutoff
      b(max) as also its spatial average, and we discuss the ensuing corrections to the
      Coulomb logarithm due to the improved values of b(max). Finally, we present the
      pertinent <lambda> values, averaged over a Maxwellian distribution function,
      which are needed for applications of the ballistic model for collisions.

PMID- 11970022
TI  - Thomson scattering of coherent diffraction radiation by an electron bunch.
AB  - This paper considers the process of Thomson scattering of coherent diffraction
      radiation (CDR) produced by the preceding electron bunch in the accelerator onto
      one of the subsequent bunches. It is shown that the yield of scattered hard
      photons is proportional to N(3)(e), where N(e) is the number of electrons per
      bunch. A geometry is chosen for the CDR generation and an expression is obtained
      for the scattered-photon spectrum, with regard to the geometry used, that depends
      explicitly on the bunch size. A technique is proposed for measuring the bunch
      length using scattered radiation characteristics.

PMID- 11970023
TI  - Thermalization of an intense, space-charge-dominated electron beam in a long
      focusing channel.
AB  - A continuous electron beam with a correlated emittance will eventually
      thermalize. Initially, the beam emittance for an intense, high-brightness, space
      charge-dominated beam will oscillate, but after a sufficiently long time, it will
      reach an equilibrium value. The emittance oscillations are due to coherent
      transverse plasma oscillations in the beam and are a manifestation of periodic
      energy exchange between potential and kinetic energies. The beam eventually
      attains an equilibrium emittance, as the beam equipartitions the kinetic and
      potential energies. This equipartioning is reached as the beam thermalizes due to
      a form of Landau damping of the radial oscillations at different radial positions
      within the beam. Slight differences in the transverse plasma oscillation
      frequency for different radial positions lead to incoherence in the oscillations.
      In this paper, we calculate the equilibrium time scales required for
      equipartioning. We show that the equilibrium emittance scalings and magnitude can
      be predicted by conservation of energy considerations. In addition, we show that,
      in the space-charge dominated regime, there is a correspondence between the
      energy-conservation approach and the kinematic approach.

PMID- 11970024
TI  - Cyclotron-resonance maser in a periodically loaded quadrupole transmission line.
AB  - A cyclotron-resonance maser (CRM) is implemented in a periodic quadrupole
      waveguide. The device oscillates at the fundamental and high harmonics of the
      cyclotron frequency. This CRM employs a tenuous low-energy electron beam (
      approximately 10 keV, 0.2 A). The periodic structure consists of an array of
      disks along the quadrupole transmission line, hence it combines both azimuthal
      and axial periodicities. This waveguide responds as a band-pass filter (BPF) with
      uniformly spaced passbands. The CRM is tuned to operate when the cyclotron
      harmonic frequencies coincide with the waveguide passbands. Microwave emission is
      observed at the first passband ( approximately 2.4 GHz), and simultaneously at
      the second and third harmonics in the corresponding BPF passbands ( approximately
      4.9 and approximately 7.4 GHz, respectively). A polarized detector reveals the
      circular polarization of the em wave inside the tube. The results of this
      experiment may lead to the development of novel CRM harmonic generators and CRM
      arrays.

PMID- 11970025
TI  - Growing-and-decaying mode solution to the Davey-Stewartson equation.
AB  - The growing-and-decaying mode solution to the Davey-Stewartson equation are
      presented, which describe the long time evolution of the Benjamin-Feir unstable
      mode in two dimensions. A solution consisting of a line soliton and a growing-and
      decaying mode shows that the Benjamin-Feir unstable mode does not destroy the
      structure of the line soliton. The breather solution and rational growing-and
      decaying mode solution are also presented.

PMID- 11970026
TI  - Existence of optical solitons on wavelength division multiplexed beams in a
      nonlinear fiber.
AB  - A simple analytic expression for the initial fundamental optical solitons on
      wavelength division multiplexed (WDM) beams in a nonlinear fiber has been found.
      For an ideal fiber with no loss and uniform group-velocity dispersion (GVD) in
      the anomalous GVD region, the initial form is [1+2(M-1)](-1/2) sech(tau), where M
      is the number of WDM beams and tau is the normalized time. Computer simulation
      shows that these initial pulses on WDM beams in this fiber will propagate
      undistorted without change in their shapes for arbitrarily long distances. The
      discovery of the existence of solitons on WDM beams presents the ultimate goal
      for optical fiber communication on multiple wavelength beams in a single fiber.

PMID- 11970027
TI  - Bifurcation picture for gap solitons in nonlinear modulated systems.
AB  - We investigate the problem of nonlinear wave propagation in periodic media. Four
      different classes of periodic nonlinear media are taken into consideration: a
      nonlinear diatomic elastic chain, modulated nonlinear optical media, a diatomic
      easy-axis ferromagnetic chain, and an easy-plane antiferromagnet in an external
      magnetic field. The main result of our work is a qualitative analysis of all
      kinds of small amplitude soliton excitations with frequencies lying in the gap
      and near the gap of the linear wave spectrum. We also study the evolution of the
      system phase portrait and the bifurcation picture of the soliton solutions under
      changes of the medium parameters.

PMID- 11970028
TI  - Suppression and enhancement of soliton switching during interaction in
      periodically twisted birefringent fibers.
AB  - Soliton interaction in periodically twisted birefringent optical fibers has been
      analyzed analytically with reference to soliton switching. For this purpose we
      construct the exact general two-soliton solution of the associated coupled system
      and investigate its asymptotic behavior. Using the results of our analytical
      approach we point out that the interaction can be used as a switch to suppress or
      to enhance soliton switching dynamics, if one injects a multisoliton as an input
      pulse in the periodically twisted birefringent fiber.

PMID- 11970029
TI  - Nonlinearity of Pancharatnam's geometric phase in polarizing interferometers.
AB  - Earlier investigations show a time-variable nonlinear shift of the fringe pattern
      in a polarizing interferometer while rotating a polarizer at the exit. This
      effect was identified as Pancharatnam's geometrical phase and proposed for
      applications in interferometry and fast optical switching devices. A heterodyne
      analysis attributes moving fringes to a frequency difference between the
      interfering beams; thus changing fringe velocities point to a dynamic frequency
      development within the period of the uniformly rotating analyzer. This
      explanation offends the intuition and we undertake an experimental and
      theoretical investigation of the effect to solve the paradox. We determine, e.g.,
      the complete frequency and mode spectrum of an arbitrary state of polarization P0
      behind a rotating linear analyzer and behind a rotating arbitrary linear
      birefringent plate. We find that, in spite of a fast changing phase in the
      interferometer, no other (higher) frequency components appear in the spectral
      distribution of the intensity at the exit than the double of the rotary frequency
      of the analyzer: phase nonlinearities are compensated for by intensity changes.
      Only a phase-sensitive detector like an array of photodetectors is able to
      observe the nonlinearity of Pancharatnam's geometrical phase. A single detector
      only finds a sinusoidal intensity variation. Our insight into these relations
      leads us to two new applications of Pancharatnam's phase: supersensitivity of a
      polarizing double beam interferometer with a video camera acting as a phase
      detector and external tuning of a Fizeau interferometer.

PMID- 11970030
TI  - Soliton evolution and radiation loss for the sine-Gordon equation.
AB  - An approximate method for describing the evolution of solitonlike initial
      conditions to solitons for the sine-Gordon equation is developed. This method is
      based on using a solitonlike pulse with variable parameters in an averaged
      Lagrangian for the sine-Gordon equation. This averaged Lagrangian is then used to
      determine ordinary differential equations governing the evolution of the pulse
      parameters. The pulse evolves to a steady soliton by shedding dispersive
      radiation. The effect of this radiation is determined by examining the linearized
      sine-Gordon equation and loss terms are added to the variational equations
      derived from the averaged Lagrangian by using the momentum and energy
      conservation equations for the sine-Gordon equation. Solutions of the resulting
      approximate equations, which include loss, are found to be in good agreement with
      full numerical solutions of the sine-Gordon equation.

PMID- 11970031
TI  - Reshaping of femtosecond pulses by the Gouy phase shift.
AB  - It is shown that because of the phase anomaly a femtosecond pulse propagates on
      the optical axis with a velocity greater than c in the vicinity of the focus not
      only for large but also small values of the Fresnel number. The group velocity is
      calculated and its physical meaning discussed. Analytical expressions are derived
      for the electric field. The causality of the system is proved. The mechanism of
      the superluminality is a reshaping process caused by the interference. Contrary
      to other superluminal phenomena, the superluminal propagation occurs in a
      classically not forbidden region.

PMID- 11970032
TI  - Calculation of the heat-source function in photophoresis of aggregated spheres.
AB  - We present theoretical results for the source function in photophoresis of an
      arbitrary aggregate of spheres that are homogeneous and isotropic piecewise. This
      source function directly represents the distribution of electric fields inside
      the spheres. Our calculation is based on a rigorous analytic solution to the
      radiative multisphere-scattering problem developed recently [Y.-l. Xu, Appl. Opt.
      34, 4573 (1995); 36, 9496 (1997); Phys. Lett. A 249, 30 (1998)]. When an
      aggregate degenerates to a single sphere, the results are exactly the same as
      those given by the Mie theory. We also discuss the numerical techniques necessary
      for obtaining an accurate numerical solution for the source function.

PMID- 11970033
TI  - Generalized Griffith criterion for dynamic fracture and the stability of crack
      motion at high velocities.
AB  - We use Eshelby's energy momentum tensor of dynamic elasticity to compute the
      forces acting on a moving crack front in a three-dimensional elastic solid
      [Philos. Mag. 42, 1401 (1951)]. The crack front is allowed to be any curve in
      three dimensions, but its curvature is assumed small enough so that near the
      front the dynamics is locally governed by two-dimensional physics. In this case
      the component of the elastic force on the crack front that is tangent to the
      front vanishes. However, both the other components, parallel and perpendicular to
      the direction of motion, do not vanish. We propose that the dynamics of cracks
      that are allowed to deviate from straight line motion is governed by a vector
      equation that reflects a balance of elastic forces with dissipative forces at the
      crack tip, and a phenomenological model for those dissipative forces is advanced.
      Under certain assumptions for the parameters that characterize the model for the
      dissipative forces, we find a second order dynamic instability for the crack
      trajectory. This is signaled by the existence of a critical velocity V(c) such
      that for velocities V<V(c) the motion is governed by K(II)=0, while for V>V(c) it
      is governed by K(II) not equal to 0. This result provides a qualitative
      explanation for some experimental results associated with dynamic fracture
      instabilities in thin brittle plates. When deviations from straight line motion
      are suppressed, the usual equation of straight line crack motion based on a
      Griffiths-like criterion is recovered.

PMID- 11970034
TI  - Asymmetric partially coherent solitons in saturable nonlinear media.
AB  - We investigate theoretically properties of partially coherent solitons in optical
      nonlinear media with slow saturable nonlinearity. We have found numerically that
      such a medium can support spatial solitons which are asymmetric in shape and are
      composed of only a finite number of modes associated with the self-induced
      waveguide. It is shown that these asymmetric spatial solitons can propagate many
      diffraction lengths without changes, but that collisions change their shape and
      may split them apart.

PMID- 11970035
TI  - Algorithms for Brownian dynamics computer simulations: multivariable case.
AB  - Several Brownian numerical schemes for treating stochastic differential equations
      at the position Langevin level are analyzed from the point of view of their
      algorithmic efficiency for large-N systems. The algorithms are tested using model
      colloidal fluids of particles interacting via the Yukawa potential. Limitations
      in the conventional Brownian dynamics algorithm are shown and it is demonstrated
      that much better accuracy for dynamical and static quantities can be achieved
      with an algorithm based on the stochastic expansion and second-order stochastic
      Runge-Kutta algorithms. The importance of the various terms in the stochastic
      expansion is analyzed, and the relative merits of second-order algorithms are
      discussed.

PMID- 11970036
TI  - Monte Carlo dynamics in global optimization.
AB  - Several very different optimization problems are studied by using the fixed
      temperature Monte Carlo dynamics and found to share many common features. The
      most surprising result is that the cost function of these optimization problems
      itself is a very good stochastic variable to describe the complicated Monte Carlo
      processes. A multidimensional problem can therefore be mapped into a one
      dimensional diffusion problem. This problem is either solved by direct numerical
      simulation or by using the Fokker-Planck equations. Above certain temperatures,
      the first passage time distribution functions of the original Monte Carlo
      processes are reproduced. At low temperatures, the first passage time has a path
      dependence and the single-stochastic-variable description is no longer valid.
      This analysis also provides a simple method to characterize the energy
      landscapes.

PMID- 11970037
TI  - Self-averaging of random and thermally disordered diluted Ising systems.
AB  - Self-averaging of singular thermodynamic quantities at criticality for randomly
      and thermally diluted three-dimensional Ising systems has been studied by the
      Monte Carlo approach. Substantially improved self-averaging is obtained for
      critically clustered (critically thermally diluted) vacancy distributions in
      comparison with the observed self-averaging for purely random diluted
      distributions. Critically thermal dilution, leading to maximum relative self
      averaging, corresponds to the case when the characteristic vacancy ordering
      temperature (theta) is made equal to the magnetic critical temperature for the
      pure three-dimensional (3D) Ising systems (T(3D)(c)). For the case of a high
      ordering temperature (theta>>T(3D)(c)), the self-averaging obtained is comparable
      to that in a randomly diluted system.

PMID- 11970038
TI  - Nonextensive foundation of Levy distributions.
AB  - A deep connection between the ubiquity of Levy distributions in nature and the
      nonextensive thermal statistics introduced a decade ago has been established
      recently [Tsallis et al., Phys. Rev. Lett. 75, 3589 (1995)], by using
      unnormalized q-expectation values. It has just been argued on physical grounds
      that normalized q-expectation values should be used instead. We revisit, within
      this more appropriate scheme, the Levy problem and verify that the relevant
      analytic results become sensibly simplified, whereas the basic physics remains
      unchanged.

PMID- 11970039
TI  - Generalized Stokes-Einstein relation for liquid metals near freezing.
AB  - Deviations from a Stokes-Einstein relation between the self-diffusion coefficient
      D and shear viscosity eta for liquid metals near freezing are shown to correlate
      with a net transit parameter xi introduced recently by Wallace [Phys. Rev. E 58,
      538 (1998)] in a two-parameter model of D. Brief comments are made on the single
      exception of In, for the seven liquid metals for which suitable experimental data
      are available.

PMID- 11970040
TI  - Coarse-graining analysis of the Berreman anchoring.
AB  - By means of a coarse-graining technique, we derive the effective anchoring energy
      of a nematic liquid crystal in contact with a macroscopically corrugated surface
      imposing a weak degenerate planar anchoring. For coarse-grained nematic
      director's profiles that vary only in the direction perpendicular to the average
      surface's plane, our results generalize those already known by including the
      anisotropy of the elastic constants. In the general case, on the contrary, we
      show that extra surface gradient terms appear that generally are not negligible.

PMID- 11970041
TI  - Dense suspensions and supercooled liquids: dynamic similarities.
AB  - Dense suspensions and supercooled, glass-forming, fragile Lennard-Jones liquids
      near T(g) should display similar relaxational and rheological behavior based on
      dynamical heterogeneities (actually, clusters of correlated, mobile particles
      embedded among the ordinary, bulk particles). Near structural arrest, we expect
      the shear-thinning onset to vanish as the inverse bulk-beta relaxation time.
      Connection to mechanical properties of granular media near random loose packing
      is briefly considered.

PMID- 11970042
TI  - Cyclotron-resonance maser in a magnetic mirror.
AB  - A cyclotron-resonance maser (CRM) experiment is performed in a high-gradient
      magnetic field using a low-energy electron beam ( approximately 10 keV/1 A). The
      magnetic field exceeds 1.63 T, which corresponds to a 45-GHz cyclotron frequency.
      The CRM radiation output is observed in much lower frequencies, between 6.6 and
      20 GHz only. This discrepancy is explained by the finite penetration depth of the
      electrons into the growing magnetic field, as in a magnetic mirror. The electrons
      emit radiation at the local cyclotron frequency in their reflection point from
      that magnetic mirror; hence, the radiation frequency depends mostly on the
      initial electron energy. A conceptual reflex gyrotron scheme is proposed in this
      paper, as a CRM analogue for the known reflex klystron.

PMID- 11970043
TI  - Longitudinal instability for a purely inductive wake function.
AB  - A purely inductive wake function was the only known case where a solution of the
      Haissinski equation did not exist beyond a certain threshold. This is due to the
      ill-defined treatment of the wake function. The solution is proved to exist
      beyond the threshold, if we define the wake function physically. The threshold of
      the stability for the solution exists but is lower than the former "threshold."

PMID- 11970044
TI  - Long-wave and short-wave asymptotics in nonlinear dispersive systems.
AB  - In this paper we study the interplay between short- and long-space scales in the
      context of conservative dispersive systems. We consider model systems in (1+1)
      dimensions that admit both long- and short-wavelength solutions in the linear
      regime. A nonlinear analysis of these systems is constructed, making use of
      multiscale expansions. We show that the equations governing the lowest order
      involve only short-wave properties and that the long-wave effects to leading
      order are determined by a secularity elimination procedure.

PMID- 11970045
TI  - Improved numerical approach for the time-independent Gross-Pitaevskii nonlinear
      Schrodinger equation.
AB  - In the present work, we improve a numerical method, developed to solve the Gross
      Pitaevkii nonlinear Schrodinger equation. A particular scaling is used in the
      equation, which permits us to evaluate the wave-function normalization after the
      numerical solution. We have a two-point boundary value problem, where the second
      point is taken at infinity. The differential equation is solved using the
      shooting method and Runge-Kutta integration method, requiring that the asymptotic
      constants, for the function and its derivative, be equal for large distances. In
      order to obtain fast convergence, the secant method is used.

PMID- 11970046
TI  - Stationary state in a two-temperature model with competing dynamics.
AB  - A two-dimensional half-filled lattice gas model with nearest-neighbor attractive
      interaction is studied where particles are coupled to two thermal baths at
      different temperatures T1 and T2. The hopping of particles is governed by the
      heat bath at temperature T1 with probability p and the other heat bath (T2) with
      probability 1-p independently of the hopping direction. On a square lattice the
      vertical and horizontal interfaces become unstable while interfaces are stable in
      the diagonal directions. As a consequence, particles condense into a tilted
      square in the novel ordered state. The p dependence of the resulting
      nonequilibrium stationary state is studied by a Monte Carlo simulation and
      dynamical mean-field approximation as well.

PMID- 11970047
TI  - Active width at a slanted active boundary in directed percolation.
AB  - The width W of the active region around an active moving wall in a directed
      percolation process diverges at the percolation threshold p(c) as W approximately
      Aepsilon(-nu( parallel)) ln(epsilon(0)/epsilon), with epsilon=p(c)-p, epsilon(0)
      a constant, and nu( parallel)=1.734 the critical exponent of the characteristic
      time needed to reach the stationary state xi( parallel) approximately epsilon(
      nu(parallel)). The logarithmic factor arises from screening the statistically
      independent needle shaped subclusters in the active region. Numerical data
      confirm this scaling behavior.

PMID- 11970048
TI  - Evidence against a three-phase point in a binary hard-core lattice model.
AB  - Using Monte Carlo simulation, Van Duijneveldt and Lekkerkerker [Phys. Rev. Lett.
      71, 4264 (1993)] found gas-liquid-solid behavior in a simple two-dimensional
      lattice model with two types of hard particles. The same model is studied here by
      means of numerical transfer-matrix calculations, focusing on the finite-size
      scaling of the gaps between the largest few eigenvalues. No evidence for a gas
      liquid transition is found. We discuss the relation of the model with a solvable
      restricted solid-on-solid model of which the states obey the same exclusion
      rules. Finally, a detailed analysis of the relation with the dilute three-state
      Potts model strongly supports the tricritical point rather than a three-phase
      point.

PMID- 11970049
TI  - Generating functionals for harmonic expectation values of paths with fixed end
      points: Feynman diagrams for nonpolynomial interactions.
AB  - We introduce a general class of generating functionals for the calculation of
      quantum-mechanical expectation values of arbitrary functionals of fluctuating
      paths with fixed end points in configuration or momentum space. The generating
      functionals are calculated explicitly for the harmonic oscillator with time
      dependent frequency, and used to derive a smearing formula for correlation
      functions of polynomial and nonpolynomial functions of time-dependent positions
      and momenta. This formula summarizes the effect of quantum fluctuations, and
      serves to derive generalized Wick rules and Feynman diagrams for perturbation
      expansions of nonpolynomial interactions.

PMID- 11970050
TI  - Dynamics of money.
AB  - We present a dynamical many-body theory of money in which the value of money is a
      time dependent "strategic variable" that is chosen by the individual agents. The
      value of money in equilibrium is not fixed by the equations, and thus represents
      a continuous symmetry. The dynamics breaks this continuous symmetry by fixating
      the value of money at a level which depends on initial conditions. The
      fluctuations around the equilibrium, for instance in the presence of noise, are
      governed by the "Goldstone modes" associated with the broken symmetry. The idea
      is illustrated by a simple network model of monopolistic vendors and buyers.

PMID- 11970051
TI  - Fractal behavior in quantum statistical physics.
AB  - The properties of an ideal gas of spinless particles are investigated by using
      the path integral formalism. It is shown that the quantum paths exhibit a fractal
      character which remains unchanged in the relativistic domain provided the
      creation of new particles is avoided, and the Brownian motion remains the
      stochastic process associated with the quantum paths. These results are obtained
      by using a special representation of the Klein-Gordon wave equation. On the
      quantum paths the relation between velocity and momentum is not the usual one.
      The mean square value of the velocity depends on the time needed to define the
      velocity and its value shows the interplay between pure quantum effects and
      thermodynamics. The fractal character is also investigated starting from wave
      equations by analyzing the evolution of a Gaussian wave packet via the Hausdorff
      dimension. Both approaches give the same fractal character in the same limit. It
      is shown that the time that appears in the path integral behaves like an ordinary
      time, and the key quantity is the time interval needed for the thermostat to give
      to the particles a thermal action equal to the quantum of action. Thus, the
      partition function calculated via the path integral formalism also describes the
      dynamics of the system for short time intervals. For low temperatures, it is
      shown that a time-energy uncertainty relation is verified at the end of the
      calculations. The energy involved in this relation has not a thermodynamic
      meaning but results from the fact that the particles do not follow the equations
      of motion along the paths. The results suggest that the density matrix obtained
      by quantification of the classical canonical distribution function via the path
      integral formalism should not be totally identical to that obtained via the usual
      route.

PMID- 11970052
TI  - Exact expression for the diffusion propagator in a family of time-dependent
      anharmonic potentials.
AB  - We have obtained the exact expression of the diffusion propagator in the time
      dependent anharmonic potential V(x,t)=1 / 2a(t)x(2)+b ln x. The underlying
      Euclidean metric of the problem allows us to obtain analytical solutions for a
      whole family of the elastic parameter a(t), exploiting the relation between the
      path integral representation of the short time propagator and the modified Bessel
      functions. We have also analyzed the conditions for the appearance of a nonzero
      flow of particles through the infinite barrier located at the origin (b<0).

PMID- 11970053
TI  - Image restoration using the chiral Potts spin glass.
AB  - We report on the image reconstruction (IR) problem by making use of the random
      chiral q-state Potts model, whose Hamiltonian possesses the same gauge invariance
      as the usual Ising spin glass model. We show that the pixel representation by
      means of the Potts variables is suitable for the gray-scale level image which
      cannot be represented by the Ising model. We find that the IR quality is highly
      improved by the presence of a glassy term, besides the usual ferromagnetic term
      under random external fields, as very recently pointed out by Nishimori and Wong.
      We give the exact solution of the infinite range model with q=3, the three-gray
      scale-level case. In order to check our analytical result and the efficiency of
      our model, two-dimensional Monte Carlo simulations have been carried out on real
      world pictures with three and eight gray-scale levels.

PMID- 11970054
TI  - Escape from a fluctuating system: a master equation and trapping approach.
AB  - We present a general solution for the mean exit time in a system with on-site
      fluctuations between two configurations described by a master equation. The
      coupled configurations represent a spatially discretized version of an escape
      over a fluctuating barrier [C. R. Doering and J. C. Gadoua, Phys. Rev. Lett. 69,
      2318 (1992)], and passage through modulating channels. Based on the general
      properties of the mean exit time, we obtain a simple solution for a coupled
      "birth" and "death" case that exhibits resonant activation. Within this exactly
      solvable model we derive analytically the optimal fluctuating rate, which is
      sensitive to the initial condition and scales as 1/n, where n is the system size.
      Our approach unifies a number of escape problems and points towards the
      generality of resonant activation.

PMID- 11970055
TI  - Disordered Markovian Brownian ratchets.
AB  - A model of a Brownian ratchet coupled to a heat bath and driven by a
      nonequilibrium Poisson white noise is discussed. The formula describing a
      generated current in terms of the statistical properties of a possible irregular
      or random potential is derived within the small nonequilibrium noise
      approximation and illustrated by a few concrete examples. The perturbation
      technique for Hilbert space operators is used as a mathematical tool.

PMID- 11970056
TI  - Exact density profile of a stochastic reaction-diffusion process.
AB  - We calculate exactly the time dependent density profile of a one-dimensional
      stochastic reaction-diffusion process of hard-core particles subjected to the
      reactions AA <--> OO and AO <--> OA. The solution is based on the fundamental
      property that the evolution operator, defined over an appropriate vector space,
      transforms vectors with n kinks into vectors with n or n+2 kinks, only. In this
      space, a basis vector is represented by a string of plus and minus signs and a
      kink is defined as a pair of opposite signs. The exact time dependent profiles
      are calculated for the cases of uncorrelated initial states that are
      translational invariant as well as initial states that are inhomogeneous in
      space.

PMID- 11970057
TI  - Line defects of a two-component vector order parameter.
AB  - The line density of line defects in terms of a two-component vector order
      parameter are obtained from the definition of topological charges of line
      defects. The spatial structure and bifurcation of line defects in three
      dimensional space are also studied from the topological properties of the two
      component vector order parameter. The branch conditions for generating,
      annihilating, colliding, splitting, and merging of line defects are obtained
      according to the properties of the two-component vector order parameter itself.
      It is found that the velocities of line defects are infinite when they are being
      annihilated or generated, which is obtained only from the topological properties
      of the two-component vector order parameter.

PMID- 11970058
TI  - Arrested states formed on quenching spin chains with competing interactions and
      conserved dynamics.
AB  - We study the effects of rapidly cooling to T=0 a spin chain with conserved
      dynamics and competing interactions. Depending on the degree of competition, the
      system is found to get arrested in different kinds of metastable states. The most
      interesting of these has an inhomogeneous mixture of interspersed active and
      quiescent regions. In this state, the steady-state autocorrelation function
      decays as a stretched exponential approximately exp[-(t/tau(0))(1/3)], and there
      is a two-step relaxation to equilibrium when the temperature is raised slightly.

PMID- 11970059
TI  - Time to failure of hierarchical load-transfer models of fracture.
AB  - The time to failure, T, of dynamical models of fracture for a hierarchical load
      transfer geometry is studied. Using a probabilistic strategy and juxtaposing
      hierarchical structures of height n, we devise an exact method to compute T, for
      structures of height n+1. Bounding T, for large n, we are able to deduce that the
      time to failure tends to a nonzero value when n tends to infinity. This numerical
      conclusion is deduced for both power law and exponential breakdown rules.

PMID- 11970060
TI  - Criticality of D=2 and D=3 Ising models: cluster structure versus populations.
AB  - The energy and the specific heat of two- and three-dimensional Ising systems are
      analyzed in terms of cluster properties. The energy and the specific heat are
      decomposed into two components, which are defined by quantities pertaining to
      cluster populations and cluster structure expressed in terms of average cluster
      perimeters. It is shown that the structural component of the energy as well as of
      the specific heat represents the dominant contribution. Indications are presented
      that the critical exponent of structural and populational components of specific
      heat matches the exponent of the entire specific heat.

PMID- 11970061
TI  - Application of cellular automata to N-body systems.
AB  - A two-dimensional cellular automaton model is introduced to deal with the
      dynamics of a finite system of particles whose interactions are simulated by two
      body step potentials. The method is illustrated for a potential approximating the
      standard Lennard-Jones potential, representative for the problem of heavy ion
      collisions in nuclear physics. From the cellular automaton dynamics thermodynamic
      equilibrium state variables are introduced in the usual way. The numerical
      experiments indicate the occurrence of a phase transition. Macroscopically the
      transition is marked by a singularity in the equation of state; microscopically
      it manifests itself by the formation of clusters of particles of all sizes,
      obeying a mass distribution in the form of a power law of exponent 1.35.

PMID- 11970062
TI  - Nonuniversal quantities from dual renormalization group transformations.
AB  - Using a simplified version of the renormalization group (RG) transformation of
      Dyson's hierarchical model, we show that one can calculate all the nonuniversal
      quantities entering into the scaling laws by combining an expansion about the
      high-temperature fixed point with a dual expansion about the critical point. The
      magnetic susceptibility is expressed in terms of two dual quantities transforming
      covariantly under an RG transformation and has a smooth behavior in the high
      temperature limit. Using the analogy with Hamiltonian mechanics, the simplified
      example discussed here is similar to the anharmonic oscillator, while more
      realistic examples can be thought of as coupled oscillators, allowing resonance
      phenomena.

PMID- 11970063
TI  - Contribution of vaporization and boiling to thermal-spike sputtering by ions or
      laser pulses.
AB  - Here we consider what, in our terminology, we designate as normal vaporization,
      normal boiling, and phase explosion. In the case of vaporization, one is dealing
      with the emission of particles (atoms or molecules) from the extreme outer
      surface of either a solid or liquid for any temperature exceeding 0 K. In the
      case of boiling, one is (at least ideally) dealing with heterogeneously nucleated
      bubbles which diffuse to the outer surface of a liquid or solid and then escape,
      the latter being possible for temperatures equal to or exceeding the boiling
      temperature (T(b)). In the case of phase explosion one is dealing with the
      consequences of what happens when a liquid approaches the thermodynamic critical
      temperature (T(tc) or T(c)), and massive homogeneous nucleation takes place.
      Although these three mechanisms have been reviewed in reasonable detail in recent
      work, we will here present evidence, apparently not previously considered, that
      boiling, whether the distance scale is atomically small (5-15 nm, as for laser
      pulse impact on a metal in the absence of thermal diffusion) or much larger, has
      a prohibitive kinetic obstacle because it requires bubble diffusion if the
      bubbles are formed other than at the outer surface. That is to say, boiling will
      never be a significant process whether with ion or laser-pulse impact. This
      leaves vaporization and phase explosion as the only possible thermal-spike
      processes capable of expelling material from an ion- or laser-pulse bombarded
      surface in a significant quantity. But even with vaporization it can be shown
      that a kinetic obstacle, although not as severe as for boiling, will enter. The
      final result is that only phase explosion will normally be relevant for
      sufficiently short time scales.

PMID- 11970064
TI  - Lattice-gas model driven by Hubbard electrons.
AB  - Self-consistent Monte Carlo simulations are undertaken for a lattice-gas model
      which is driven by the free energy of electrons described by a Hubbard model with
      electronic hopping restricted to ions at nearest-neighbor sites. Our previous
      work, an independent-electron tight-binding lattice-gas model (bcc or fcc), is
      modified to introduce two effects: the disorder of the dense system and, more
      importantly, the role of the electronic correlation. The first effect is achieved
      using an fcc lattice, but restricted so an occupied site can have no more than
      eight, instead of twelve, occupied nearest-neighbor sites. To treat correlations,
      the electronic intra-atomic repulsion is, at first, included via the Gutzwiller
      approximation at finite temperature; this approach is simple enough to be solved
      for all cases in the large, disordered systems used in our Monte Carlo
      simulations but can still give a good qualitative representation of the main
      effects of the electronic correlations. Then, the exact treatment of the Hubbard
      model for clusters with up to six atoms is integrated into the calculation. We
      obtain vapor-liquid coexistence curves and then, approximations to the electronic
      conductivities and paramagnetic susceptibilities at coexistence conditions. This
      simple model is, in part, motivated by experiments on the alkali-metal fluids.

PMID- 11970065
TI  - Unified projection operator formalism in nonequilibrium statistical mechanics.
AB  - The method of projection operators, which plays an important role in the field of
      nonequilibrium statistical mechanics, has been established with the use of the
      Liouville-von Neumann equation for a density matrix to eliminate irrelevant
      information from a whole system. We formulate a unified and general projection
      operator method for dynamical variables. The main features of our formalism
      parallel those for the Liouville-von Neumann equation. (1) Two types of basic
      equations, time-convolution and time-convolutionless decompositions, are
      systematically obtained without specifying a projection operator. (2) Expansion
      formulas for both decompositions are also obtained. (3) Problems incorporating a
      time-dependent Liouville operator can be flexibly treated. We apply the formulas
      to problems in random frequency modulation and low field resonance. In
      conclusion, our formalism yields a more direct and easier means of determining
      the average time evolution of an operator than the one for the Liouville-von
      Neumann equation.

PMID- 11970066
TI  - Spatial instabilities in reaction random walks with direction-independent
      kinetics.
AB  - We study spatial instabilities in reacting and diffusing systems, where diffusion
      is modeled by a persistent random walk instead of the usual Brownian motion.
      Perturbations in these reaction walk systems propagate with finite speed, whereas
      in reaction-diffusion systems localized disturbances affect every part instantly,
      albeit with heavy damping. We present evolution equations for reaction random
      walks whose kinetics do not depend on the particles' direction of motion. The
      homogeneous steady state of such systems can undergo two types of transport
      driven instabilities. One type of bifurcation gives rise to stationary spatial
      patterns and corresponds to the Turing instability in reaction-diffusion systems.
      The other type occurs in the ballistic regime and leads to oscillatory spatial
      patterns; it has no analog in reaction-diffusion systems. The conditions for
      these bifurcations are derived and applied to two model systems. We also analyze
      the stability properties of one-variable systems and find that small wavelength
      perturbations decay in an oscillatory manner.

PMID- 11970067
TI  - Quasicrystals in a monodisperse system.
AB  - We investigate the formation of a two-dimensional quasicrystal in a monodisperse
      system, using molecular dynamics simulations of hard-sphere particles interacting
      via a two-dimensional square-well potential. We find that more than one stable
      crystalline phase can form for certain values of the square-well parameters.
      Quenching the liquid phase at a very low temperature, we obtain an amorphous
      phase. By heating this amorphous phase, we obtain a quasicrystalline structure
      with fivefold symmetry. From estimations of the Helmholtz potentials of the
      stable crystalline phases and of the quasicrystal, we conclude that the observed
      quasicrystal phase can be the stable phase in a specific range of temperatures.

PMID- 11970068
TI  - Coarsening in a driven Ising chain with conserved dynamics.
AB  - We study the low-temperature coarsening of an Ising chain subject to spin
      exchange dynamics and a small driving force. This dynamical system reduces to a
      domain diffusion process, in which entire domains undergo nearest-neighbor
      hopping, except for the shortest domains-dimers-which undergo long-range hopping.
      This system exhibits anomalous ordering dynamics due to the existence of two
      characteristic length scales: the average domain length L(t) approximately t(1/2)
      and the average dimer hopping distance l(t) approximately square root[L(t)]
      approximately t(1/4). As a consequence of these two scales, the density of short
      domains decays as t(-5/4), instead of the t(-3/2) decay that would arise from
      pure domain diffusion.

PMID- 11970069
TI  - Reaction kinetics of diffusing particles injected into a reactive substrate.
AB  - We analyze the kinetics of trapping (A+B-->B) and annihilation (A+B-->0)
      processes on a one-dimensional substrate with homogeneous distribution of
      immobile B particles while the A particles are supplied by a localized source.
      For the imperfect reaction case, we analyze both problems by means of a
      stochastic model and compare the results with numerical simulations. In addition,
      we present the exact analytical results of the stochastic model for the case of
      perfect trapping.

PMID- 11970070
TI  - Cluster size diversity, percolation, and complex systems.
AB  - Diversity of cluster size has been used as a measurement of complexity in several
      systems that generate a statistical distribution of clusters. Using Monte Carlo
      simulations, we present a statistical analysis of the cluster size diversity and
      the number of clusters generated on randomly occupied lattices for the Euclidean
      dimensions 1 to 6. A tuning effect for diversity of cluster size and critical
      probabilities associated with the maximum diversity and the maximum number of
      clusters are reported. The probability of maximum diversity is related to the
      percolation threshold and several scaling relations between the variables
      measured are reported. The statistics of cluster size diversity has important
      consequences in the statistical description of the Universe as a complex system.

PMID- 11970071
TI  - Correlations of eigenvectors for non-Hermitian random-matrix models.
AB  - We establish a general relation between the diagonal correlator of eigenvectors
      and the spectral Green's function for non-Hermitian random-matrix models in the
      large-N limit. We apply this result to a number of non-Hermitian random-matrix
      models and show that the outcome is in good agreement with numerical results.

PMID- 11970072
TI  - Self-organized criticality in a nutshell.
AB  - In order to gain insight into the nature of self-organized criticality (SOC), we
      present a minimal model exhibiting this phenomenon. In this analytically solvable
      model, the state of the system is fully described by a single-integer variable.
      The system organizes in its critical state without external tuning. We derive
      analytically the probability distribution of durations of disturbances
      propagating through the system. As required by SOC, this distribution is scale
      invariant and follows a power law over several orders of magnitude. Our solution
      also reproduces the exponential tail of the distribution due to finite size
      effects. Moreover, we show that large avalanches are suppressed when stabilizing
      the system in its critical state. Interestingly, avalanches are affected in a
      similar way when driving the system away from the critical state. With this
      model, we have reduced SOC dynamics to a leveling process as described by
      Ehrenfest's famous flea model.

PMID- 11970073
TI  - Triangular anisotropies in driven diffusive systems: reconciliation of up and
      down.
AB  - Deterministic coarse-grained descriptions of driven diffusive systems (DDS) have
      been hampered by apparent inconsistencies with the kinetic Ising models of DDS.
      In the evolution towards the driven steady-state, "triangular" anisotropies in
      the two systems point in opposite directions with respect to the drive field. We
      show that this is nonuniversal behavior in the sense that the triangular
      anisotropy "flips" with local modifications of the Ising interactions. The sign
      and magnitude of the triangular anisotropy also vary with temperature. We have
      also flipped the anisotropy of coarse-grained models, though not yet at the
      latest stages of evolution. Our results illustrate the comparison of
      deterministic coarse-grained and stochastic Ising DDS studies to identify
      universal phenomena in driven systems. Coarse-grained systems are particularly
      attractive in terms of analysis and computational efficiency.

PMID- 11970074
TI  - Cluster analysis and finite-size scaling for Ising spin systems.
AB  - Based on the connection between the Ising model and a correlated percolation
      model, we calculate the distribution function for the fraction (c) of lattice
      sites in percolating clusters in subgraphs with n percolating clusters, f(n)(c),
      and the distribution function for magnetization (m) in subgraphs with n
      percolating clusters, p(n)(m). We find that f(n)(c) and p(n)(m) have very good
      finite-size scaling behavior and that they have universal finite-size scaling
      functions for the model on square, plane triangular, and honeycomb lattices when
      aspect ratios of these lattices have the proportions 1:square root[3]/2:square
      root[3]. The complex structure of the magnetization distribution function p(m)
      for the system with large aspect ratio could be understood from the independent
      orientations of two or more percolation clusters in such a system.

PMID- 11970075
TI  - Entropy production fluctuation theorem and the nonequilibrium work relation for
      free energy differences.
AB  - There are only a very few known relations in statistical dynamics that are valid
      for systems driven arbitrarily far-from-equilibrium. One of these is the
      fluctuation theorem, which places conditions on the entropy production
      probability distribution of nonequilibrium systems. Another recently discovered
      far from equilibrium expression relates nonequilibrium measurements of the work
      done on a system to equilibrium free energy differences. In this paper, we derive
      a generalized version of the fluctuation theorem for stochastic, microscopically
      reversible dynamics. Invoking this generalized theorem provides a succinct proof
      of the nonequilibrium work relation.

PMID- 11970076
TI  - Coherent stochastic resonance in the case of two absorbing boundaries.
AB  - The coherent stochastic resonance is observed and studied with a multistep
      periodic signal in a continuous medium having two absorbing boundaries. The
      general features of this process are exhibited. The universal features at the
      resonance point are demonstrated. The kinetic behaviors around the resonance
      point are also presented.

PMID- 11970077
TI  - Network of characterizing functions for stationary populations.
AB  - A variety of open systems in nature and society exist under dynamic equilibrium,
      maintained by statistical counterbalance between the entering and leaving of
      individuals and the stationarity of the exchange processes. A network of
      functions characterizing the dynamics of such a stationary population is
      established and discussed, which allows the mutual transference of system
      properties without the need of any explicit information about the microdynamic
      processes. In order to illustrate the potential benefit of these interdependence
      relations, examples taken from diverse branches of research (adsorption and
      reaction kinetics, demographic analysis, and coronary blood flow diagnosis) are
      given.

PMID- 11970078
TI  - Dynamic behavior of the Ziff-Gulari-Barshad model on fractal lattices: the
      influence of the order of ramification.
AB  - A catalytic reaction model, the Ziff-Gulari-Barshad model, is studied on fractal
      lattices, and the influence of the order of ramification of the lattice on the
      dynamic behavior of the model is investigated. According to the Monte Carlo
      simulation results, the order of ramification of the lattice is not crucial to
      the existence of the continuous transition. This is different from the
      equilibrium phase transitions in discrete-symmetry spin models (such as the Ising
      model). Our results indicate that the criterion of the existence of the reactive
      phase may be complicated.

PMID- 11970079
TI  - Complexity of routes to chaos and global regularity of fractal dimensions in
      bimodal maps.
AB  - The dual-star composition rule of doubly superstable (DSS) sequences presents a
      complete renormalizable algebraic structure for studying Feigenbaum's metric
      universality and self-similar classification of DSS sequences in symbolic
      dynamics of bimodal maps of the interval. Here an important feature is that the
      complete combinations of up- and down-star products create all the generalized
      Feigenbaum's routes of transitions to chaos. These routes can be classified into
      two types: one consists of countably infinitely many regular routes which
      preserve Feigenbaum's metric universality; another consists of uncountably
      infinitely many universal nonscaling routes described by the irregularly mixed
      dual-star products, which break Feigenbaum's asymptotically convergent metric
      universality although they are structurally universal. The combinatorial
      complexity of dual-star products may increase the grammatical complexity of
      languages of symbolic dynamics. Moreover, it is found that there exists a global
      regularity between the fractal dimensions d and the scaling factors
      [alpha(C),alpha(D)] for Feigenbaum-type attractors:
      d(Z)log(/Z/)/alpha(C)(Z)alpha(D)(Z)/=beta((2)), where beta((2)) is independent of
      the concrete DSS sequences Z.

PMID- 11970080
TI  - Characteristic distributions of finite-time Lyapunov exponents.
AB  - We study the probability densities of finite-time or local Lyapunov exponents in
      low-dimensional chaotic systems. While the multifractal formalism describes how
      these densities behave in the asymptotic or long-time limit, there are
      significant finite-size corrections, which are coordinate dependent. Depending on
      the nature of the dynamical state, the distribution of local Lyapunov exponents
      has a characteristic shape. For intermittent dynamics, and at crises, dynamical
      correlations lead to distributions with stretched exponential tails, while for
      fully developed chaos the probability density has a cusp. Exact results are
      presented for the logistic map, x-->4x(1-x). At intermittency the density is
      markedly asymmetric, while for "typical" chaos, it is known that the central
      limit theorem obtains and a Gaussian density results. Local analysis provides
      information on the variation of predictability on dynamical attractors. These
      densities, which are used to characterize the nonuniform spatial organization on
      chaotic attractors, are robust to noise and can, therefore, be measured from
      experimental data.

PMID- 11970081
TI  - General form of coupling leading to synchronization of oscillating dynamical
      systems.
AB  - There are numerous examples in nature where oscillating or pulsing physical and
      biological systems automatically synchronize. Here we pose the question: Is there
      a general type of coupling that leads to such synchronization? It is demonstrated
      on numerous examples that dissipative coupling results in synchronization for a
      variety of systems.

PMID- 11970082
TI  - Largest Lyapunov exponent in molecular systems. II: Quaternion coordinates and
      application to methane clusters.
AB  - We present a numerical procedure for extracting Lyapunov characteristic exponents
      from classical molecular-dynamics simulations of molecular systems. The
      theoretical frame chosen to describe the orientational degrees of freedom is the
      quaternions scheme. We apply the method to small methane clusters. Two different
      model potentials are used to investigate the role of internal molecular motion on
      the nonlinear dynamics, and several parameters are calculated to study the
      thermodynamics and chaotic dynamics of these clusters. Evidence is found for a
      solidlike to plasticlike phase transition occurring with the release of the
      orientational degrees of freedom, at low temperatures below the melting point.
      The largest Lyapunov exponent increases significantly during this transition, but
      it exhibits no particular variation during melting.

PMID- 11970083
TI  - Colored-noise-induced chaotic array synchronization.
AB  - The effect of a time-correlated Gaussian noise on one-dimensional arrays
      consisting of diffusively coupled chaotic cells is analyzed. A resonance effect
      between the time scale of the chaotic attractor and the colored Gaussian noise
      has been found. As well, depending on the number of cells, coupling, and noise
      strength, an improvement of the synchronization or a poor synchronization between
      cells within the array can occur for some values of the time correlation. These
      nonlinear cooperative effects are studied in terms of a linear stability analysis
      around the uniform synchronized behavior.

PMID- 11970084
TI  - Chaotic advection in compressible helical flow.
AB  - Compressible helical flow with div v not equal to 0 drastically increases the
      area of chaotic dynamics and mixing properties when the helicity parameter is
      spatially dependent. We show that the density dependence on the z coordinate can
      be incorporated in new variables in a way that leads to a Hamiltonian formulation
      of the system. This permits the application of various important results like the
      Kolmogorov-Arnold-Moser theory and, particularly, an understanding of why and in
      which sense the compressible helical flow is "more chaotic" than the
      incompressible one. Simulation demonstrates this property for an analog of the
      ABC flow. An interesting type of the dynamical system with "dense" island chains
      is described.

PMID- 11970085
TI  - Synchronization of diffusively coupled oscillators near the homoclinic
      bifurcation.
AB  - It has been known that a diffusive coupling between two limit cycle oscillations
      typically leads to the in-phase synchronization and also that it is the only
      stable state in the weak-coupling limit. Recently, however, it has been shown
      that the coupling of the same nature can result in the distinctive dephased
      synchronization when the limit cycles are close to the homoclinic bifurcation,
      which often occurs especially for the neuronal oscillators. In this paper we
      propose a simple physical model using the modified van der Pol equation, which
      unfolds the generic synchronization behaviors of the latter kind and in which one
      may readily observe changes in the sychronization behaviors between the
      distinctive regimes as well. The dephasing mechanism is analyzed both
      qualitatively and quantitatively in the weak-coupling limit. A general form of
      coupling is introduced and the synchronization behaviors over a wide range of the
      coupling parameters are explored to construct the phase diagram using the
      bifurcation analysis.

PMID- 11970086
TI  - Test your surrogate data before you test for nonlinearity.
AB  - The schemes for the generation of surrogate data in order to test the null
      hypothesis of linear stochastic process undergoing nonlinear static transform are
      investigated as to their consistency in representing the null hypothesis. In
      particular, we pinpoint some important caveats of the prominent algorithm of
      amplitude adjusted Fourier transform surrogates (AAFT) and compare it to the
      iterated AAFT, which is more consistent in representing the null hypothesis. It
      turns out that in many applications with real data the inferences of nonlinearity
      after marginal rejection of the null hypothesis were premature and have to be
      reinvestigated taking into account the inaccuracies in the AAFT algorithm, mainly
      concerning the mismatching of the linear correlations. In order to deal with such
      inaccuracies, we propose the use of linear together with nonlinear polynomials as
      discriminating statistics. The application of this setup to some well-known real
      data sets cautions against the use of the AAFT algorithm.

PMID- 11970087
TI  - Desynchronization of chaos in coupled logistic maps.
AB  - When identical chaotic oscillators interact, a state of complete or partial
      synchronization may be attained in which the motion is restricted to an invariant
      manifold of lower dimension than the full phase space. Riddling of the basin of
      attraction arises when particular orbits embedded in the synchronized chaotic
      state become transversely unstable while the state remains attracting on the
      average. Considering a system of two coupled logistic maps, we show that the
      transition to riddling will be soft or hard, depending on whether the first orbit
      to lose its transverse stability undergoes a supercritical or subcritical
      bifurcation. A subcritical bifurcation can lead directly to global riddling of
      the basin of attraction for the synchronized chaotic state. A supercritical
      bifurcation, on the other hand, is associated with the formation of a so-called
      mixed absorbing area that stretches along the synchronized chaotic state, and
      from which trajectories cannot escape. This gives rise to locally riddled basins
      of attraction. We present three different scenarios for the onset of riddling and
      for the subsequent transformations of the basins of attraction. Each scenario is
      described by following the type and location of the relevant asynchronous cycles,
      and determining their stable and unstable invariant manifolds. One scenario
      involves a contact bifurcation between the boundary of the basin of attraction
      and the absorbing area. Another scenario involves a long and interesting series
      of bifurcations starting with the stabilization of the asynchronous cycle
      produced in the riddling bifurcation and ending in a boundary crisis where the
      stability of an asynchronous chaotic state is destroyed. Finally, a phase diagram
      is presented to illustrate the parameter values at which the various transitions
      occur.

PMID- 11970088
TI  - Distributions of transition matrix elements in classically mixed quantum systems.
AB  - The quantitative contributions of a mixed phase space to the mean characterizing
      the distribution of diagonal transition matrix elements and to the variance
      characterizing the distributions of nondiagonal transition matrix elements are
      studied. It is shown that the mean can be expressed as the sum of suitably
      weighted classical averages along an ergodic trajectory and along the stable
      periodic orbits. Similarly, it is shown that the values of the variance are well
      reproduced by the sum of the suitably weighted Fourier transforms of classical
      autocorrelation functions along an ergodic trajectory and along the stable
      periodic orbits. The illustrative numerical computations are done in the
      framework of a hydrogen atom in a strong magnetic field, for three different
      values of the scaled energy.

PMID- 11970089
TI  - Nonperiodic orbit sums in Weyl's expansion for billiards.
AB  - Weyl's expansion for the asymptotic mode density of billiards consists of the
      area, length, curvature, and corner terms. The area term has been associated with
      the so-called zero-length orbits. Here, closed nonperiodic paths corresponding to
      the length and corner terms are constructed.

PMID- 11970090
TI  - Experimental versus numerical eigenvalues of a Bunimovich stadium billiard: a
      comparison.
AB  - We compare the statistical properties of eigenvalue sequences for a gamma=1
      Bunimovich stadium billiard. The eigenvalues have been obtained in two ways: one
      set results from a measurement of the eigenfrequencies of a superconducting
      microwave resonator (real system), and the other set is calculated numerically
      (ideal system). We show influence of mechanical imperfections of the real system
      in the analysis of the spectral fluctuations and in the length spectra compared
      to the exact data of the ideal system. We also discuss the influence of a family
      of marginally stable orbits, the bouncing ball orbits, in two microwave stadium
      billiards with different geometrical dimensions.

PMID- 11970091
TI  - Front formation in an active scalar equation.
AB  - We study the formation of thermal fronts in an active scalar equation that is
      similar to the Euler equation. For a particular initial condition, an earlier
      candidate for finite-time blowup, the front forms in a generalized self-similar
      way with constant hyperbolicity at the center. The behavior belongs to a class of
      scenarios for which finite-time blowup is impossible. A systematic exploration of
      many different initial conditions reveals no evidence of singular solutions.

PMID- 11970092
TI  - Statistical-mechanical predictions and Navier-Stokes dynamics of two-dimensional
      flows on a bounded domain.
AB  - In this paper the applicability of a statistical-mechanical theory to freely
      decaying two-dimensional (2D) turbulence on a bounded domain is investigated. We
      consider an ensemble of direct numerical simulations in a square box with stress
      free boundaries, with a Reynolds number that is of the same order as in
      experiments on 2D decaying Navier-Stokes turbulence. The results of these
      simulations are compared with the corresponding statistical equilibria,
      calculated from different stages of the evolution. It is shown that the
      statistical equilibria calculated from early times of the Navier-Stokes evolution
      do not correspond to the dynamical quasistationary states. At best, the global
      topological structure is correctly predicted from a relatively late time in the
      Navier-Stokes evolution, when the quasistationary state has almost been reached.
      This failure of the (basically inviscid) statistical-mechanical theory is related
      to viscous dissipation and net leakage of vorticity in the Navier-Stokes dynamics
      at moderate values of the Reynolds number.

PMID- 11970093
TI  - Generalized density-functional theory: extended weighted density approaches.
AB  - A third-order density-functional theory is introduced by an approach that may be
      used to find density-functional theories to any higher-order accuracy provided
      only that known homogeneous state correlation functions are utilized as input. It
      is constructed from the required knowledge of a single weight function at each
      order. By way of application results are presented for the melting of classical
      hard spheres using functionals accurate to a third-order functional Taylor series
      in the homogeneous limit. Within the framework of the modified weighted density
      approximation, there is a uniform improvement in the solid phase-free energies,
      pressures and melting parameters, and further improvement also results when these
      functionals are optimized in a way that utilizes the close packing limit. The
      sensitivity of the results to existing and proposed models of the third-order
      direct correlation function is discussed.

PMID- 11970094
TI  - Crossover between ordinary and normal transitions in two dimensional critical
      Ising films.
AB  - We investigate two dimensional critical Ising films of width L with surface
      fields H(1)=H(L) in the crossover between ordinary (H(1)=0) and normal
      (H(1)=infinity) transitions. Using exact transfer-matrix diagonalization and
      density matrix renormalization-group (DMRG) methods, we calculate magnetization
      profiles m(z), the excess magnetization Gamma, and the analog of the solvation
      force f(solv) as functions of H1 for several L. Scaling functions of the above
      quantities deviate substantially from their asymptotic forms at fixed points for
      a broad region of the scaling variable LH21 approximately L/l(1), where l(1) is
      the length induced by the surface field H1. The scaling function for /f(solv)/
      has a deep minimum near LH(2)(1)=1, which is about one order of magnitude smaller
      than its value at both fixed points (the "Casimir" amplitude). For weak H1
      (l(1)>L) the magnetization profile has a maximum at the center of the film, and
      f(solv) decays much faster than L-2. For stronger H1 (1<l(1)<L), the
      magnetization has two maxima at a distance approximately l(1) from the walls, and
      the solvation force decays much slower than L-2. For L>>l(1) the solvation force
      decays according to the universal power law f(solv) approximately L(-2). The
      results of the approximate DMRG method show remarkable agreement with the exact
      ones.

PMID- 11970095
TI  - Nonlinear equation for curved nonstationary flames and flame stability.
AB  - A time-dependent nonlinear equation for a nonstationary curved flame front of an
      arbitrary expansion coefficient is derived under the assumptions of a small but
      finite flame thickness and weak nonlinearity. On the basis of the derived
      equation, stability of two-dimensional curved stationary flames propagating in
      tubes with ideally adiabatic and slip walls is studied. The stability analysis
      shows that curved stationary flames become unstable for sufficiently wide tubes.
      The obtained stability limits are in a good agreement with the results of
      numerical simulations of flame dynamics and with semiqualitative stability
      analysis of curved stationary flames. Possible outcomes of the obtained
      instability at the nonlinear stage are discussed. The instability may result in
      extra wrinkles at a flame front close to the stability limits and in self
      turbulization of the flame far from the limits. The self-turbulization can also
      be interpreted as a fractal structure. The fractal dimension of a flame front and
      velocity of a self-turbulized flame are evaluated.

PMID- 11970096
TI  - Integral equation theory for fluids ordered by an external field: separable
      interactions.
AB  - The structural and thermodynamical properties of classical fluids orientationally
      ordered by an external field are investigated by means of integral equation
      theories. A general theoretical framework for handling these theories is
      developed and detailed for the particular case of separable interactions between
      fluid particles. This approach is then illustrated for the case of two (off
      lattice) models: the ferromagnetic Heisenberg model and a simple liquid crystal
      model, for which the numerical solution of integral equations such as the Percus
      Yevick, the hypernetted chain, and the reference hypernetted chain closure
      equations are presented and compared with Monte Carlo simulation results and the
      analytical solution of the mean spherical approximation. The zero-field case is
      also examined, and the spontaneous ordering is analyzed in detail, mainly in what
      concerns the appearance of infinite wavelength singularity in the Ornstein
      Zernike equation and the relation with the one-body closure equations and the
      long range orientational ordering that occurs. In particular, it is shown that
      the Wertheim one-body closure equation appears as a sum rule compatible with the
      Ornstein-Zernike equation. The relation between the elastic constant and the long
      range tail of the pair correlation function is made explicit. In particular, the
      long range behavior of the various terms in the expansion of the pair correlation
      function is depicted. The numerical investigation of the two models shows that it
      is not possible to discriminate between the four integral equations, as to which
      one would be the most accurate in all cases. The general trends in the
      thermodynamical and structural properties seem to indicate that the Percus-Yevick
      approximation is generally better in the strong ordering case, whereas the
      reference hypernetted chain approximation might be better suited to the study of
      the isotropic phase and the low ordering regimes.

PMID- 11970097
TI  - Droplet vaporization at critical conditions: long-time convective-diffusive
      profiles along the critical isobar.
AB  - The heating of a cold fluid package introduced, at critical conditions, in a
      hotter environment of the same fluid at the critical pressure is analyzed.
      Critical anomalies of the fluid transport properties as well as an arbitrary
      equation of state are taken into account. In unconfined microgravity conditions
      and for times much longer than the characteristic acoustic time, the heat
      transfer becomes a convective-diffusive isobaric transient process. An asymptotic
      theory valid in the limit of very small ratio between the fluid densities in the
      hot and cold regions is developed. The divergency of the thermal conductivity
      kappa at the critical temperature controls the heat transfer to the cold region.
      In the present model it is shown that there exists a well defined border, denoted
      by R(t), delimiting two distinguishable regions. The outer region extends from
      the far field down to R(t) where the critical temperature T(c) is reached. There,
      the temperature gradient vanishes due to the divergency of kappa. Thus, heat does
      not penetrate in the inner cold region where the temperature remains equal to
      T(c). The heating of the initially cold fluid package takes place by the
      recession of the border R(t). The model predicts a temperature profile in the
      outer region which is quasisteady in a reference system receding with R(t). It is
      shown that R2(t) decreases linearly with time. The recession velocity and thus
      the vaporization time are obtained as a function of the geometry and of the far
      field conditions. Furthermore, the restrictions imposed by the long-time isobaric
      hypothesis are analyzed.

PMID- 11970098
TI  - High dimensionality as an organizing device for classical fluids.
AB  - The Mayer diagrammatic expansion for a classical pair-interacting fluid in
      thermal equilibrium is cast in a form particularly appropriate to high
      dimensional space. At asymptotically high dimensionality, the series, when it
      converges, is dominated by a single term. Focusing upon repulsive interactions,
      the dominant term belongs to a ring diagram and can have either sign, but when
      negative, the series must diverge. The nature of the divergence is found
      explicitly for hard core interactions, and analytic extension in density obtained
      by summing up the dominant ring contributions. The result is that a second virial
      truncation remains valid at densities much higher than that at which the series
      diverges. Corrections first appear in the vicinity of a particle volume-scaled
      density of 1 / 2(e/2)(1/2) per dimension, and produce a spinodal in the equation
      of state. Suggestions are made as to elucidating the resulting phase transition.

PMID- 11970099
TI  - Kinematic dynamos surrounded by a stationary conductor.
AB  - We investigate kinematic dynamos in cylinders and spheres surrounded by an
      insulator. The flow volume is divided into an inner region, in which the
      conducting fluid is in motion, and an outer region enclosing the inner one, in
      which the conductor is at rest. The dependence of the critical magnetic Reynolds
      number on the thickness of the outer conducting shell is discussed as well as
      implications for the design of experimental dynamos.

PMID- 11970100
TI  - Cylinder wakes in flowing soap films.
AB  - We present an experimental characterization of cylinder wakes in flowing soap
      films. From instantaneous velocity and thickness fields, we find the vortex
      shedding frequency, mean-flow velocity, and mean-film thickness. Using the
      empirical relationship between the Reynolds and Strouhal numbers obtained for
      cylinder wakes in three dimensions, we estimate the effective soap-film viscosity
      and its dependence on film thickness. We also compare the decay of vorticity with
      that in a simple Rankine vortex model with a dissipative term to account for air
      drag.

PMID- 11970101
TI  - Plumes and waves in two-dimensional turbulent thermal convection.
AB  - We have conducted a high-resolution, two-dimensional direct numerical simulation
      of Rayleigh-Benard convection with stress-free and periodic boundary conditions
      at a Rayleigh (Ra) number of 10(8) and Prandtl (Pr) number of unity. An aspect
      ratio three box has been considered. A single cell has been used as the initial
      condition. First, the flow develops into time-dependent convection with a strong
      asymmetry and highly convoluted thermal plumes delineating a large-scale
      circulation. Smaller thermal plumes detach from the boundary layer and extend
      over the entire cell, creating a local inversion of the temperature gradient
      adjacent to the boundary layers. Then the conditions leading to the formation of
      internal waves are fulfilled, as the local Richardson number decreases
      sufficiently small to cross the linear threshold of Ri=0.25. Together with the
      strong shear, convective rolls with a Kelvin-Helmholtz wavelike character are
      produced. The secondary boundary layer itself becomes unstable and produces
      smaller plumes. At later times, the large-scale circulation is destroyed and the
      internal waves disappear. A Reynolds number, based on the global scale, of
      Re=500, is attained at this stage. Only isolated thermal plumes and vortices are
      present. Thus, internal waves can be generated at finite Prandtl number fluids
      for sufficiently high Ra in the presence of a large-scale circulation. Spectral
      analysis reveals that the kinetic energy decays with a logarithmic slope of -3,
      while the logarithmic slope of the thermal variance has a value of around -5 / 3.

PMID- 11970102
TI  - Moving droplets on asymmetrically structured surfaces.
AB  - It is shown theoretically and experimentally that a liquid droplet can move on a
      surface structured with a locally asymmetric pattern when a breathing of the drop
      is induced by external means. Two different situations can be envisioned: a drop
      whose volume is modulated and a drop whose equilibrium contact angle is switched
      between two extreme values. This last case was experimentally investigated using
      electric fields acting on water droplets in castor oil. The main trends of the
      theory are verified although a quantitative analysis would necessitate either a
      simpler experimental geometry or a more elaborate model. The results are
      discussed with a miniaturization of the setup in mind which would have important
      potential applications in the field of integrated analysis systems.

PMID- 11970103
TI  - Nematic ordering of rigid rods in a gravitational field.
AB  - The isotropic-to-nematic transition in an athermal solution of long rigid rods
      subject to a gravitational (or centrifugal) field is theoretically considered in
      the Onsager approximation. The new feature emerging in the presence of gravity is
      a concentration gradient that coupled with the nematic ordering. For rodlike
      molecules this effect becomes noticeable at centrifugal acceleration g
      approximately 10(3)-10(4) m/s(2), while for biological rodlike objects, such as
      tobacco mosaic virus, the effect is important even for normal gravitational
      acceleration conditions. Rods are concentrated near the bottom of the vessel,
      which sometimes leads to gravity induced nematic ordering. The concentration
      range corresponding to phase separation increases with increasing g. In the
      region of phase separation the local rod concentration, as well as the order
      parameter, follow a step function with height.

PMID- 11970104
TI  - Field-induced phase transitions in antiferroelectric liquid crystals.
AB  - A theoretical study is made of the process by which an antiferroelectric smectic
      liquid crystal undergoes a field-induced transition to ferroelectric alignment.
      We find that for cells of moderate thickness the initial departure from
      antiferroelectric alignment occurs as a continuous Freedericksz transition. The
      following transition from partial alignment to complete ferroelectric ordering
      may occur as either a first-order or continuous transition, depending on the
      relative strength of some of the model parameters. The case where the transition
      is continuous provides a possible mechanism for some recently observed
      thresholdless transitions in these systems.

PMID- 11970105
TI  - Freedericksz transition thresholds in pretilted nematic slabs.
AB  - The appearance of periodically distorted director structures in pretilted nematic
      slabs with rigid boundary conditions above the Freedericksz transition is
      determined as a function of the Frank elastic constant ratios K(2)/K(1),
      K(3)/K(1), and the pretilt angle. It is found that the periodically distorted
      state can be reached either directly from the undistorted state on increasing the
      magnetic field or indirectly through the homogeneously distorted state. A new
      threshold field for the transition undistorted state, homogeneously distorted
      state was found for specific ranges of the Frank elastic constant ratios
      K(2)/K(1), K(3)/K(1), and the pretilt angle.

PMID- 11970106
TI  - Effect of the electric conductivity on the drift velocity of the cholesteric
      fingers of the second type in confined geometry.
AB  - We show that the drift velocity of the cholesteric fingers of the second species
      in ac electric field strongly depends on the conductivity of the liquid crystal
      chosen and exponentially vanishes above a cutoff frequency we found to be equal
      (within a numerical factor close to 1) to the charge relaxation frequency of the
      sample. We further show that the drift velocity is proportional to the applied
      electric field, provided that the confinement ratio is kept constant.

PMID- 11970107
TI  - Semianalytical calculation of the Rouse dynamics of randomly branched polymers.
AB  - We present a semianalytical approach to the determination of the dynamic
      properties of randomly branched polymers under the Rouse approximation. The
      principal procedure is based on examining an eigenvalue spectrum which represents
      the average dynamic behavior of various structures. The calculated spectra show
      that the eigenvalue distribution is random even within a single structure, which
      in turn produces a continuous spectrum of values for the entire class. The
      autocorrelation function for the square of the radius of gyration was calculated
      based on these spectra, which confirms that the dynamics are nonexponential as
      earlier reported. A universal stretched exponent is also found in this study.

PMID- 11970108
TI  - Counting defects in an instantaneous quench.
AB  - We consider the formation of defects in a nonequilibrium second-order phase
      transition induced by an instantaneous quench to zero temperature in a type II
      superconductor. We perform a full nonlinear simulation where we follow the
      evolution in time of the local order parameter field. We determine how far into
      the phase transition theoretical estimates of the defect density based on the
      Gaussian approximation yield a reliable prediction for the actual density. We
      also characterize quantitatively some aspects of the out of equilibrium phase
      transition.

PMID- 11970109
TI  - Melting of polydisperse colloidal crystals in nonequilibrium.
AB  - The influence of a time-dependent oscillatory external field on the melting
      transition of a polydisperse colloidal crystal is examined by theory and computer
      simulation. In a monodisperse crystal the field just induces an overall dynamical
      mode which does not affect the melting line. For a polydisperse sample, on the
      other hand, the field shifts the melting line towards smaller temperatures.
      Combining a solid cell approach and a Lindemann criterion in nonequilibrium, a
      simple theory is presented showing that the temperature shift scales with the
      square of the relative polydispersity. The theory is in reasonable agreement with
      nonequilibrium Brownian dynamics computer simulations.

PMID- 11970110
TI  - Phase diagrams of electric-field-induced aggregation in conducting colloidal
      suspensions.
AB  - To develop a theory for electric-field-driven phase transitions in concentrated
      suspensions, we extended our microscopic theory [Phys. Rev. E 52, 1669, (1995);
      54, 5428, (1996)] beyond the dilute regime. Based on the model of the Maxwell
      Wagner interfacial polarization of colloids, our theory overcomes the limitations
      of Brillouin's formula for the electric energy of conducting materials which is
      applicable only for negligibly small energy dissipation and slow time variations
      of the field. We found that the phase diagrams of "the particle concentration vs
      the electric field strength" for colloids are similar to the phase diagrams for
      the first-order phase separation in quenched conventional binary systems with a
      high-temperature miscibility gap. This explains why a variety of colloids exhibit
      similar field-induced aggregation patterns. Our theory provides a reasonable
      interpretation of the available experimental data on field-induced aggregation
      phenomena in electrorheological fluids and aqueous suspensions, whereas currently
      used theoretical models are in variance with many of the data. The theoretical
      results enable one to trace how the variations of the electrical properties of
      the constituent materials influence the topology of the suspension phase diagram
      and to evaluate the effects of the field strength and frequency on the particle
      aggregation.

PMID- 11970112
TI  - Theory of monolayers with boundaries: exact results and perturbative analysis.
AB  - Domains and bubbles in tilted phases of Langmuir monolayers contain a class of
      textures known as boojums. The boundaries of such domains and bubbles may display
      either cusplike features or indentations. We derive analytic expressions for the
      textures within domains and surrounding bubbles, and for the shapes of the
      boundaries of these regions. The derivation is perturbative in the deviation of
      the bounding curve from a circle. This method is not expected to be accurate when
      the boundary suffers large distortions, but it does provide important clues with
      regard to the influence of various energetic terms on the order-parameter texture
      and the shape of the domain or bubble bounding curve. We also look into the
      effects of thermal fluctuations, which include a sample-size-dependent effective
      line tension.

PMID- 11970111
TI  - Diffusive mobility of fractal aggregates over the entire Knudsen number range.
AB  - We determine the effective mobility radius for fractal aggregate particles. Our
      method is to use static light scattering to measure the radius of gyration R(g)
      of the aggregates, and dynamic light scattering to measure the diffusion
      coefficient hence the mobility radius R(m). The range of our results can be
      specified by the Knudsen number Kn, which is the mean free path of the medium
      molecules divided by the radius of the aggregate. Our results apply to the entire
      range of Kn from the continuum limit (Kn=0) to the free molecular limit (Kn>>1).
      In the continuum regime we find R(m)/R(g)=0.97+/-0.05 when the aggregate fractal
      dimension is D(f) approximately 2.15, and 0.70+/-0.05 when D(f) approximately
      1.75. The latter result is independent of Kn for Kn < or approximately 1.3. The
      free molecular mobility goes as R(m)=aN(0.44+/-0.03), where a is the monomer
      radius and N is the number of monomers per aggregate. Since R(g) approximately
      aN(1/D(f)), R(m)/R(g) is not a constant when Kn is large. We find for all Kn that
      the functionality of R(m)/R(g) must always begin with the correct N-->1 limit,
      and this affects experimental observation.

PMID- 11970113
TI  - Aggregation and chimney formation during the solidification of ammonium chloride.
AB  - Experiments study large-scale pattern formation during the growth of ammonium
      chloride (NH4Cl) from solution in a thin (Hele-Shaw) geometry. In particular a
      solid-liquid mixture ("mushy layer") forms in which growing solid NH4Cl crystals
      form a solid network interspersed with liquid. There are different ways that the
      mushy layer can be formed, however. If the cell is heated from below and cooled
      from above, thermal convection generates large-scale recirculating flows that
      carry seed crystals from the upper (cold) boundary to the (warmer) side and
      bottom boundaries. Ballistic deposition of these seed crystals leads to
      aggregation patterns with significant voids (filled with liquid) with a wide
      range of length scales. If the cell is cooled from below with a warm environment,
      the solid NH4Cl grows dendritically without deposition, resulting in a compact
      mushy layer. Plume convection within this mushy layer produces one or two well
      defined "chimneys." If the environment is cool (comparable to the liquidus
      temperature of the solution), the mushy layer forms by a combination of dendritic
      growth and ballistic deposition, resulting in a more permeable mushy layer and
      enhanced chimney formation. The effects of ballistic deposition are enhanced if
      the cell is tipped, in which case the voids reappear. Plume convection and
      chimney formation are dramatically enhanced in this case. Additional experiments
      are done in which fluid flows in the system are enhanced artificially to verify
      that enhancements in chimney formation are due primarily to the aggregation
      process, and not to the increases in fluid flows due to thermal and compositional
      convection.

PMID- 11970114
TI  - Fluctuations provide strong selection in Ostwald ripening.
AB  - A selection problem that appears in the Lifshitz-Slyozov (LS) theory of Ostwald
      ripening is reexamined. The problem concerns selection of a self-similar
      distribution function (DF) of the minority domains with respect to their sizes
      from a whole one-parameter family of solutions. A strong selection rule is found
      via an account of fluctuations. Fluctuations produce an infinite tail in the DF
      and drive the DF towards the "limiting solution" of LS or its analogs for other
      growth mechanisms.

PMID- 11970115
TI  - Dynamics of irregular copolymers.
AB  - Reptation dynamics of AB copolymers with irregular chemical structure are
      considered theoretically. It is shown that interactions between A and B monomers
      could result in a significant slowdown of copolymer dynamics in the disordered
      (macroscopically homogeneous) state. The dynamical copolymer length N* showing
      the crossover to the strongly retarded dynamics is calculated. It is shown that
      contour-length fluctuations (internal reptation modes) give rise to a strong
      reduction of the slowdown effect and to a strong increase of N* which becomes
      unrealistically high in the case of a genuinely random chemical structure. The
      following scaling dependence of N* is predicted for irregular block copolymers:
      N* proportional, variant delta(-8)chi(-8)n(-8)(0)N(3)(e), where delta is the
      degree of block polydispersity, chi the Flory AB interaction parameter, and n(0)
      the mean block length. The strongest dynamical effect of AB interactions is
      predicted for correlated random copolymers near the critical point related to the
      formation of microdomain superstructures.

PMID- 11970116
TI  - Light-scattering study of a supercooled epoxy resin.
AB  - The dynamics of the fragile glass-forming liquid diglycidyl ether of bisphenol-A
      was studied by depolarized Rayleigh-Brillouin light-scattering and photon
      correlation spectroscopy above the glass transition, in the temperature range
      from 261 to 473 K and in the frequency range from 1 Hz to 300 GHz. The structural
      (alpha-) relaxation process was revealed and no signature of the secondary
      relaxation previously evidenced by dielectric spectroscopy at about 0.1 GHz was
      observed. The characteristic time of the alpha process differs from that
      determined by dielectric spectroscopy of an amount, which increases with
      increasing temperature. The relaxation times were compared with viscosity data to
      test the predictions of the classic Stokes-Einstein-Debye model. The tau
      proportional, variant eta behavior was verified for dielectric data, while a
      fractional power law of viscosity tau proportional, variant eta(0.89) was
      obtained for light-scattering relaxation times, extending over more than seven
      decades in viscosity and time. This deviation of light scattering from viscosity
      data could be interpreted in terms of cooperative motion in the supercooled
      liquid with a characteristic length xi(a) proportional, variant(T-T0)(-v) where
      T(0)=229 K is the Vogel temperature and v is close to 2 / 3 which is consistent
      with the prediction of the fluctuation theory of glass transition.

PMID- 11970117
TI  - Anomalous surface diffusion of water compared to aprotic liquids in nanopores.
AB  - 1H nuclear magnetic relaxation dispersion experiments show remarkable differences
      between water and acetone in contact with microporous glass surfaces containing
      trace paramagnetic impurities. Analyzed with surface relaxation theory on a model
      porous system, the data obtained for water show that proton surface diffusion
      limited by chemical exchange with the bulk phase permits long-range effectively
      one-dimensional exploration along the pores. This magnetic-field dependence
      coupled with the anomalous temperature dependence of the relaxation rates permits
      a direct interpretation in terms of the proton translational diffusion
      coefficient at the surface of the pores. A universal rescaling applied to these
      data collected for different pore sizes and on a large variety of frequencies and
      temperatures, supports this interpretation. The analysis demonstrates that
      acetone diffuses more slowly, which increases the apparent confinement and
      results in a two-dimensional model for the molecular dynamics close to surface
      relaxation sinks. Surface-enhanced water proton diffusion, however, permits the
      proton to explore a greater spatial extent of the pore, which results in an
      apparent one-dimensional model for the diffusive motions of the water that
      dominate nuclear spin relaxation.

PMID- 11970118
TI  - Spatial correlations of mobility and immobility in a glass-forming Lennard-Jones
      liquid.
AB  - Using extensive molecular dynamics simulations of an equilibrium, glass-forming
      Lennard-Jones mixture, we characterize in detail the local atomic motions. We
      show that spatial correlations exist among particles undergoing extremely large
      ("mobile") or extremely small ("immobile") displacements over a suitably chosen
      time interval. The immobile particles form the cores of relatively compact
      clusters, while the mobile particles move cooperatively and form quasi-one
      dimensional, stringlike clusters. The strength and length scale of the
      correlations between mobile particles are found to grow strongly with decreasing
      temperature, and the mean cluster size appears to diverge near the mode-coupling
      critical temperature. We show that these correlations in the particle
      displacements are related to equilibrium fluctuations in the local potential
      energy and local composition.

PMID- 11970119
TI  - Characterization of unidirectional photopolymerization in poly(vinyl cinnamate)
      by surface optical second-harmonic generation.
AB  - Surface optical second-harmonic generation measurements were used to determine
      the change in the surface density and the surface orientational order parameter
      of the trans-cinnamoyl side groups of unidirectionally photopolymerized
      poly(vinyl cinnamate) (PVCN) films. The observed surface features were compared
      to the bulk properties of the films, which were probed by their UV absorption
      spectra and birefringence measurements. We found that the surface and the bulk
      photoreaction kinetics of the trans cinnamoyl side groups of the PVCN are very
      similar. The two photoreaction processes (trans-cis photoisomerization and photo
      induced cross linking) appear to affect the linear and nonlinear optical
      properties of the polymer differently. This may explain the discrepancy between
      the birefringence and the azimuthal anchoring force of the unidirectionally
      photopolymerized PVCN.

PMID- 11970120
TI  - Entropic rigidity of randomly diluted two- and three-dimensional networks.
AB  - In recent work, we presented evidence that site-diluted triangular central-force
      networks, at finite temperatures, have a nonzero shear modulus for all
      concentrations of particles above the geometric percolation concentration p(c).
      This is in contrast to the zero-temperature case where the (energetic) shear
      modulus vanishes at a concentration of particles p(r)>p(c). In the present paper
      we report on analogous simulations of bond-diluted triangular lattices, site
      diluted square lattices, and site-diluted simple-cubic lattices. We again find
      that these systems are rigid for all p>p(c) and that near p(c) the shear modulus
      mu approximately (p-p(c))(f), where the exponent f approximately 1.3 for two
      dimensional lattices and f approximately 2 for the simple-cubic case. These
      results support the conjecture of de Gennes that the diluted central-force
      network is in the same universality class as the random resistor network. We
      present approximate renormalization group calculations that also lead to this
      conclusion.

PMID- 11970121
TI  - Dielectric and transport properties of a supercooled symmetrical molten salt.
AB  - The liquid-glass transition of the restricted primitive model for a symmetrical
      molten salt is studied using mode-coupling theory. The transition at high
      densities is predicted to obey the Lindemann criterion for melting, and the
      charge-density peak found in neutron-scattering experiments on ionic glass
      formers is qualitatively reproduced. Frequency-dependent dielectric functions,
      shear viscosities, and dynamical conductivities of the supercooled liquid are
      presented. Comparing the latter to the diffusion constant, we find that mode
      coupling theory reproduces the Nernst-Einstein relation. The Stokes-Einstein
      radius is found to be approximately equal to the particle radius only near the
      high-density glass transition.

PMID- 11970122
TI  - Origin of density clustering in a freely evolving granular gas.
AB  - The physical mechanisms leading to the development of density inhomogeneities in
      a freely evolving low density granular gas are investigated. By means of the
      direct simulation Monte Carlo method, numerical solutions of the inelastic
      Boltzmann equation are constructed for both a perturbed system and also for an
      initially homogeneous state. Analysis of the Fourier components of the fields
      indicates that the nonlinear coupling contributions of the transversal velocity
      play a crucial role in the initial setup of clustering. A simple hydrodynamic
      model is proposed to describe what is observed in the simulations. Finally, the
      nature of the inhomogeneous state is briefly discussed.

PMID- 11970123
TI  - Phase behavior of binary hard-sphere mixtures from perturbation theory.
AB  - Using a first-order perturbation theory, we have studied the phase diagram of a
      binary mixture of hard spheres for different values of the size ratio. Recent
      models for the two-body depletion potential between large spheres are used to
      take into account the role of the small spheres. The theory predicts a complex
      phase diagram including a fluid-solid transition at high packing fraction of
      small spheres, metastability of fluid-fluid demixing, an isostructural solid
      solid transition at high packing fraction of the large spheres for sufficiently
      small values of the size ratio q of the spheres, and the tendency to sticky
      sphere behavior in the limit q-->0. The agreement with recent simulation results
      is quite good. We also show that this phenomenology was already implicit in the
      pioneering work of Asakura and Oosawa.

PMID- 11970124
TI  - Force-extension curves for a single polymer chain under varying solvent
      conditions.
AB  - We show that Langevin dynamics can be used to obtain force-extension curves for a
      single polymer chain under varying solvent conditions. We find that the chains
      obey Hooke-type and Pincus regime behavior for Theta and good solvents. However,
      in poor solvents a coil-strand coexistence is observed in the equilibrium state
      and this leads to a quite different type of deformation behavior.

PMID- 11970125
TI  - Relaxation length of a polymer chain in a quenched disordered medium.
AB  - Using Monte Carlo simulations, we study the relaxation and short-time diffusion
      of polymer chains in two-dimensional periodic arrays of obstacles with random
      point defects. The displacement of the center of mass follows the anomalous
      scaling law r(c.m.)(t)(2)=4D(*)t(beta), with beta<1, for times t<t(SS), where
      t(SS) is the time required to attain the steady state. The relaxation of the
      autocorrelation function of the chain's end-to-end vector, on the other hand, is
      well described by the stretched exponential form C(t)=exp[-(t/tau(*))(alpha)],
      where 0<alpha</=1 and tau(*)<<t(SS). However, our results also obey the
      functional form C(r(c.m.))=exp(-[r(c.m.)/lambda](2)), implying the coupling
      alpha=beta even though these exponents vary widely from system to system. We thus
      propose that it is lambda, and not the traditional length (Dtau(*))(1/2), that is
      the relevant relaxation polymer length scale in disordered systems.

PMID- 11970126
TI  - Debye-Huckel theory for interfacial geometries.
AB  - The Debye-Huckel theory for bulk electrolyte solutions is generalized to planar
      interfacial geometries, including screening effects due to mobile salt ions which
      are confined to the interface and solutions with in general different salt
      concentrations and dielectric constants on the two sides of the interface. We
      calculate the general Debye-Huckel interaction between fixed test charges, and
      analyze a number of relevant special cases as applicable to charged colloids and
      charged polymers. Salty interfaces, which are experimentally realized by
      monolayers or bilayers made of cationic and anionic surfactants or lipids, exert
      a strong attraction on charged particles of either sign at large separations from
      the interface; at short distances image-charge repulsion sets in. Likewise, the
      effective interactions between charged particles are strongly modified in the
      neighborhood of such a salty interface. On the other hand, charged particles
      which are immersed in a salt solution are repelled from the air (or a substrate)
      interface, and the interaction between two charges decays algebraically close to
      such an interface. These general results have experimentally measurable
      consequences for the adsorption of charged colloids or charged polymers at
      monolayers, solid substrates, and interfaces.

PMID- 11970127
TI  - Phase behavior of aligned dipolar hard spheres: integral equations and density
      functional results.
AB  - Using reference hypernetted chain integral equations, we investigate the phase
      behavior of a system of dipolar hard spheres with perfect orientational order. At
      low densities, the correlation functions show a strong tendency to the formation
      of head-to-tail chains. The occurrence of a condensation of the chains, as
      suggested by a recent simulation, is critically discussed. At higher densities
      the structure of the liquid phase already reflects well defined positions of the
      chains relative to each other, similar to a body-centered-tetragonal structure.
      Minimizing a density functional of the grand canonical free energy which is based
      on the liquid correlation functions, we calculate the coexistence lines at
      freezing. Interestingly, the system freezes at much lower temperatures than the
      corresponding isotropic fluid.

PMID- 11970128
TI  - Effect of geometrical confinement on the interaction between charged colloidal
      suspensions.
AB  - The effective interaction between charged colloidal particles confined between
      two planar like-charged walls is investigated using computer simulations of the
      primitive model describing asymmetric electrolytes. In detail, we calculate the
      effective force acting onto a single macroion and onto a macroion pair in the
      presence of slitlike confinement. For moderate Coulomb coupling, we find that
      this force is repulsive. Under strong-coupling conditions, however, the sign of
      the force depends on the distance to the plates and on the interparticle
      distance. In particular, the particle-plate interaction becomes strongly
      attractive for small distances which may explain the occurrence of colloidal
      crystalline layers near the plates observed in recent experiments.

PMID- 11970129
TI  - Thermodynamic and statistical studies of supersaturated ternary solutions.
AB  - The influence of chromium ions Cr3+ on properties of supersaturated aqueous
      solution of ammonium sulfate (NH4)2SO4 has been studied employing containerless
      electrodynamic levitation of single microdroplets of this solution with known
      concentration of Cr3+ ions. The water activity versus solute concentration was
      measured in three different sets of experiments corresponding to different
      initial concentrations of Cr3+ ions. Theoretical treatment of the experimental
      results obtained is developed employing the theory of supersaturated electrolyte
      solutions [Phys. Rev. E 52, 1325 (1995)]. This treatment has allowed the
      following two conclusions. First, spinodal concentration is a decreasing function
      of Cr3+ concentration. Second, solute clusters formed in the presence of Cr3+
      ions demonstrate complex behavior with respect to binding water molecules: (a) at
      low and moderate supersaturations, they bind more water molecules than clusters
      formed in the absence of an impurity; and (b) at high supersaturations, they bind
      less water molecules than clusters formed in the absence of an impurity.

PMID- 11970130
TI  - Energy landscapes, supergraphs, and "folding funnels" in spin systems.
AB  - Dynamical connectivity graphs, which describe dynamical transition rates between
      local energy minima of a system, can be displayed against the background of a
      disconnectivity graph which represents the energy landscape of the system. The
      resulting supergraph describes both dynamics and statics of the system in a
      unified coarse-grained sense. We give examples of the supergraphs for several two
      dimensional spin and protein-related systems. We demonstrate that disordered
      ferromagnets have supergraphs akin to those of model proteins whereas spin
      glasses behave like random sequences of amino acids that fold badly.

PMID- 11970131
TI  - Spheres and prolate and oblate ellipsoids from an analytical solution of the
      spontaneous-curvature fluid-membrane model.
AB  - An analytic solution for the Helfrich spontaneous curvature membrane model [H.
      Naito, M.Okuda, and Ou-Yang Zhong-Can, Phys. Rev. E 48, 2304 (1993); 54, 2816
      (1996)], which has the conspicuous feature of representing a circular biconcave
      shape, is studied. Results show that the solution in fact describes a family of
      shapes, which can be classified as (i) a flat plane (trivial case), (ii) a
      sphere, (iii) a prolate ellipsoid, (iv) a capped cylinder, (v) an oblate
      ellipsoid, (vi) a circular biconcave shape, (vii) a self-intersecting inverted
      circular biconcave shape, and (viii) a self-intersecting nodoidlike cylinder.
      Among the closed shapes (ii)-(vii), a circular biconcave shape is the one with a
      minimum of local curvature energy.

PMID- 11970132
TI  - Exact solution of an evolutionary model without aging.
AB  - We introduce an age-structured asexual population model containing all the
      relevant features of evolutionary aging theories. Beneficial as well as
      deleterious mutations, heredity, and arbitrary fecundity are present and managed
      by natural selection. An exact solution without aging is found. We show that
      fertility is associated with generalized forms of the Fibonacci sequence, while
      mutations and natural selection are merged into an integral equation which is
      solved by Fourier series. Average survival probabilities and Malthusian growth
      exponents are calculated and indicate that the system may exhibit mutational
      meltdown. The relevance of the model in the context of fissile reproduction
      groups like many protozoa and coelenterates is discussed.

PMID- 11970133
TI  - Nonlinear transfer function encodes synchronization in a neural network from the
      mammalian brain.
AB  - Synchronization is one of the mechanisms by which the brain encodes information.
      The observed synchronization of neuronal activity has, however, several levels of
      fluctuations, which presumably regulate local features of specific areas. This
      means that biological neural networks should have an intrinsic mechanism able to
      synchronize the neuronal activity but also to preserve the firing capability of
      individual cells. Here, we investigate the input-output relationship of a
      biological neural network from developing mammalian brain, i.e., the hippocampus.
      We show that the probability of occurrence of synchronous output activity (which
      consists in stereotyped population bursts recorded throughout the hippocampus) is
      encoded by a sigmoidal transfer function of the input frequency. Under this
      scope, low-frequency inputs will not produce any coherent output while high
      frequency inputs will determine a synchronous pattern of output activity
      (population bursts). We analyze the effect of the network size (N) on the
      parameters of the transfer function (threshold and slope). We found that
      sigmoidal functions realistically simulate the synchronous output activity of
      hippocampal neural networks. This outcome is particularly important in the
      application of results from neural network models to neurobiology.

PMID- 11970134
TI  - Periodic solutions and exponential stability in delayed cellular neural networks.
AB  - Some simple sufficient conditions are given ensuring global exponential stability
      and the existence of periodic solutions of delayed cellular neural networks
      (DCNNs) by constructing suitable Lyapunov functionals and some analysis
      techniques. These conditions are easy to check in terms of system parameters and
      have important leading significance in the design and applications of globally
      stable DCNNs and periodic oscillatory DCNNs. In addition, two examples are given
      to illustrate the theory.

PMID- 11970135
TI  - Nonlinear electrostatic waves in a magnetized plasma.
AB  - The modulational interaction of finite-amplitude high-frequency electrostatic
      waves propagating at an arbitrary angle to an external magnetic field with slow
      plasma motion is considered. A set of nonlinear evolution equations describing
      the interaction is obtained. New types of solitary waves propagating at near
      sonic speeds are found.

PMID- 11970136
TI  - Cross-focusing of two laser beams in a plasma.
AB  - Cross-focusing of two copropagating laser beams in a plasma is investigated using
      paraxial ray theory. If the lasers have a frequency difference equal to the
      electron plasma frequency, they can drive a large amplitude plasma wave. The
      ponderomotive force due to the plasma wave forces the plasma electrons outwards
      thereby generating a parabolic density profile giving rise to cross-focusing. The
      results show a decrease in threshold for focusing by two orders of magnitude as
      compared to focusing due to the ponderomotive force of the laser beams.

PMID- 11970137
TI  - Ion-acoustic waves in a dust-contaminated plasma.
AB  - A self-consistent theory of ion-acoustic waves in dusty gas discharge plasmas is
      presented. The plasma is contaminated by fine dust particles with variable
      charge. The stationary state of the plasma and the dispersion and damping
      characteristics of the waves are investigated accounting for ionization,
      recombination, dust charge relaxation, and dissipation due to electron and ion
      elastic collisions with neutrals and dusts, as well as charging collisions with
      the dusts.

PMID- 11970138
TI  - Nucleus-electron model for states changing from a liquid metal to a plasma and
      the Saha equation.
AB  - We extend the quantal hypernetted-chain (QHNC) method, which has been proved to
      yield accurate results for liquid metals, to treat a partially ionized plasma. In
      a plasma, the electrons change from a quantum to a classical fluid gradually with
      increasing temperature; the QHNC method applied to the electron gas is in fact
      able to provide the electron-electron correlation at an arbitrary temperature. As
      an illustrating example of this approach, we investigate how liquid rubidium
      becomes a plasma by increasing the temperature from 0 to 30 eV at a fixed normal
      ion density 1.03x10(22)/cm(3). The electron-ion radial distribution function
      (RDF) in liquid Rb has distinct inner-core and outer-core parts. Even at a
      temperature of 1 eV, this clear distinction remains as a characteristic of a
      liquid metal. At a temperature of 3 eV, this distinction disappears, and rubidium
      becomes a plasma with the ionization 1.21. The temperature variations of bound
      levels in each ion and the average ionization are calculated in Rb plasmas at the
      same time. Using the density-functional theory, we also derive the Saha equation
      applicable even to a high-density plasma at low temperatures. The QHNC method
      provides a procedure to solve this Saha equation with ease by using a recursive
      formula; the charge population of differently ionized species are obtained in Rb
      plasmas at several temperatures. In this way, it is shown that, with the atomic
      number as the only input, the QHNC method produces the average ionization, the
      electron-ion and ion-ion RDF's, and the charge population that are consistent
      with the atomic structure of each ion for a partially ionized plasma.

PMID- 11970139
TI  - Direct spectroscopic observation of multiple-charged-ion acceleration by an
      intense femtosecond-pulse laser.
AB  - We have observed evidence of the emission of energetic He-and H-like ions of
      fluorine more than 1 MeV produced via the optical field ionization (OFI) from a
      solid target irradiated by an intense I=(2-4)x10(18) W/cm(2) (60 fs, lambda=800
      nm), obliquely incident p-polarized pulse laser. The measured blue wing of
      He(alpha), He(beta), and Ly(alpha) lines of fluorine shows a feature of the
      Doppler-shifted spectrum due to the self-similar ion expansion dominated by
      superthermal electrons with the temperature T(h) approximately 100 keV. Using a
      collisional particle-in-cell simulation, which incorporates the nonlocal
      thermodynamic-equilibrium ionization including OFI, we have obtained the plasma
      temperature, line shape, and maximal energy of accelerated ions, which agree well
      with those determined from the experimental spectra. The red wing of ion spectra
      gives the temperature of bulk plasma electrons.

PMID- 11970140
TI  - Acceleration and double-peak spectrum of hot electrons in relativistic laser
      plasmas.
AB  - A spectrum equation of hot electrons in relativistic laser plasmas is derived in
      which two hot-electron population peaks appear as the laser strength parameter
      reaches a threshold. These calculations can explain the generation of very hot
      electrons with several tens of MeV energy and two hot-electron population peaks
      observed in the recent experiments.

PMID- 11970141
TI  - Performance comparison of self-focusing with 1053- and 351-nm laser pulses.
AB  - Hole boring characteristics of laser beams are studied using two different laser
      wavelengths in preformed plasmas with overdense regions. We have shown that a
      whole beam self-focusing is created in plasma with a considerable density scale
      length using a 1 microm wavelength laser. The whole beam self-focusing of this
      type could be used for guiding the ultrahigh intense laser pulse to a highly
      compressed core for studying the feasibility of a fast ignitor. There is a clear
      difference in the hole-boring characteristics between two laser wavelengths at
      1053 and 351 nm, both in the experiment and the simulation. Using the third
      harmonic laser, a whole beam self-focusing is never created. The 351-nm laser
      beam broke up into filaments resulting in plasma jets observed in our
      interferogram.

PMID- 11970142
TI  - Current drive generation based on autoresonance and intermittent trapping
      mechanisms.
AB  - Two mechanisms for generating streams of high-velocity electrons are presented.
      One has its origin in auto resonance (AR) interaction, which takes place in the
      system after a trapping conditioning stage, the second being dominated by the
      trapping process itself. These mechanisms are revealed from the study of the
      relativistic motion of an electron in a configuration consisting of two
      counterpropagating electromagnetic waves along a constant magnetic field in a
      dispersive medium. Using a Hamiltonian formalism, we have numerically solved the
      equations of motion and presented the results in a set of figures showing the
      generation of streams of electrons having high parallel velocities. Insight into
      these numerical results is gained from a theoretical analysis, which consists of
      a reformulation of the equations of motion. The operation of these mechanisms was
      found to circumvent the deterioration of the electron acceleration process that
      is characteristic for a dispersive medium, thus allowing for an effective
      generation of a current drive. Discussion of the results follows.

PMID- 11970143
TI  - Generation of powerful subnanosecond microwave pulses by intense electron bunches
      moving in a periodic backward wave structure in the superradiative regime.
AB  - Experimental results of the observation of coherent stimulated radiation from
      subnanosecond electron bunches moving through a periodic waveguide and
      interacting with a backward propagating wave are presented. The subnanosecond
      microwave pulses in Ka and W bands were generated with repetition frequencies of
      up to 25 Hz. The mechanism of microwave pulse generation was associated with self
      bunching, and the mutual influence of different parts of the electron pulse due
      to slippage of the wave with respect to the electrons; this can be interpreted as
      superradiance. The illumination of a panel of neon bulbs resulted in a finely
      structured pattern corresponding to the excitation of the TM01 mode. Observation
      of rf breakdown of ambient air, as well as direct measurements by hot-carrier
      germanium detectors, leads to an estimate of the absolute peak power as high as
      60 MW for the 300-ps pulses at 38 GHz. These results are compared with numerical
      simulations. The initial observation of 75-GHz, 10-15-MW radiation pulses with a
      duration of less than 150 ps is also reported.

PMID- 11970144
TI  - Kink-antikink interactions in the double sine-Gordon equation and the problem of
      resonance frequencies.
AB  - We studied the kink-antikink collision process for the "double sine-Gordon" (DSG)
      equation in 1+1 dimensions at different values of the potential parameter R>0.
      For small values of R we discuss the problem of resonance frequencies. We give
      qualitative explanation of the frequency shift in comparison with the frequency
      of the discrete level in the potential well of isolated kink. We show that in
      this region of the parameter R the effective long-range interaction between kink
      and antikink takes place.

PMID- 11970145
TI  - Spectral changes of light produced by scattering from disordered anisotropic
      media.
AB  - We investigate theoretically changes in the spectrum of polychromatic light
      scattered by a disordered, birefringent medium. We derive an expression for the
      spectrum of scattered light for ordinary and extraordinary incident waves within
      the accuracy of the first Born approximation. Using this result, we analyze the
      changes in the spectrum of light due to the combined action of disorder and
      anisotropy in the scattering process.

PMID- 11970146
TI  - Coupled nonlinear Schrodinger equations with cubic-quintic nonlinearity:
      Integrability and soliton interaction in non-Kerr media.
AB  - We propose an integrable system of coupled nonlinear Schrodinger equations with
      cubic-quintic terms describing the effects of quintic nonlinearity on the
      ultrashort optical soliton pulse propagation in non-Kerr media. Lax pairs,
      conserved quantities and exact soliton solutions for the proposed integrable
      model are given. The explicit form of two solitons are used to study soliton
      interaction showing many intriguing features including inelastic (shape changing
      or intensity redistribution) scattering. Another system of coupled equations with
      fifth-degree nonlinearity is derived, which represents vector generalization of
      the known chiral-soliton bearing system.

PMID- 11970147
TI  - Dissipative solitons under the action of the third-order dispersion.
AB  - We study the evolution of a solitary pulse in the cubic complex Ginzburg-Landau
      equation, including the third-order dispersion (TOD) as a small perturbation. We
      develop analytical approximations, which yield a TOD-induced velocity c of the
      pulse as a function of the ratio D of the second-order dispersion and filtering
      coefficients. The analytical predictions show agreement with the direct numerical
      simulations for two distinct intervals of D. A new feature of the pulse motion,
      which is a precursor of the transition to blowup, is presented: The pulse
      suddenly acquires a large acceleration in the reverse direction at D>D(cr)
      approximately -1.5 and without the reversal at D<D(cr). It is also demonstrated
      that the laminar-propagation distance L (before the onset of the ultimate
      turbulent stage) becomes maximum deep inside the normal-dispersion region, while
      TOD significantly increases L in the anomalous-dispersion region, where,
      otherwise, it is quite small. The model has a straightforward physical
      realization in terms of nonlinear optical fibers with losses and bandwidth
      limited amplification (gain and filtering).

PMID- 11970148
TI  - Theory of photorefractive vectorial wave coupling in cubic crystals.
AB  - We present an analytical theory of vectorial wave coupling in photorefractive
      cubic crystals which are, in general, optically active. The theory is based on
      the systematic use of the spatial symmetry properties and the apparatus of the
      Pauli operators to deal with two-dimensional vectors and matrices. It allows one
      to give a unified description of a wide spectrum of photorefractive phenomena,
      including the efficiency and polarization properties of Bragg diffraction,
      polarization two-beam coupling enhanced by ac fields, the influence of the
      photoelastic effect, etc. Applications of the theory to crystals of the sillenite
      family and to particular photorefractive phenomena are given. A good qualitative
      agreement between the theoretical predictions and experimental data for Bi12TiO20
      (BTO) crystals is shown.

PMID- 11970149
TI  - Integrating the Kuramoto-Sivashinsky equation in polar coordinates: application
      of the distributed approximating functional approach.
AB  - An algorithm is presented to integrate nonlinear partial differential equations,
      which is particularly useful when accurate estimation of spatial derivatives is
      required. It is based on an analytic approximation method, referred to as
      distributed approximating functionals (DAF's), which can be used to estimate a
      function and a finite number of derivatives with a specified accuracy. As an
      application, the Kuramoto-Sivashinsky (KS) equation is integrated in polar
      coordinates. Its integration requires accurate estimation of spatial derivatives,
      particularly close to the origin. Several stationary and nonstationary solutions
      of the KS equation are presented, and compared with analogous states observed in
      the combustion front of a circular burner. A two-ring, nonuniform counter
      rotating state has been obtained in a KS model simulation of such a burner.

PMID- 11970150
TI  - Algorithm for normal random numbers.
AB  - We propose a simple algorithm for generating normally distributed pseudorandom
      numbers. The algorithm simulates N molecules that exchange energy among
      themselves following a simple stochastic rule. We prove that the system is
      ergodic, and that a Maxwell-like distribution that may be used as a source of
      normally distributed random deviates follows in the N-->infinity limit. The
      algorithm passes various performance tests, including Monte Carlo simulation of a
      finite two-dimensional Ising model using Wolff's algorithm. It only requires four
      simple lines of computer code, and is approximately ten times faster than the Box
      Muller algorithm.

PMID- 11970151
TI  - Simulation of low-Reynolds-number flow via a time-independent lattice-Boltzmann
      method.
AB  - We present a numerical method to solve the equations for low-Reynolds-number
      (Stokes) flow in porous media. The method is based on the lattice-Boltzmann
      approach, but utilizes a direct solution of time-independent equations, rather
      than the usual temporal evolution to steady state. Its computational efficiency
      is 1-2 orders of magnitude greater than the conventional lattice-Boltzmann
      method. The convergence of the permeability of random arrays of spheres has been
      analyzed as a function of mesh resolution at several different porosities. For
      sufficiently large spheres, we have found that the convergence is quadratic in
      the mesh resolution.

PMID- 11970152
TI  - Relativistic calculations using Monte Carlo methods: one-electron systems.
AB  - Variance minimization and Monte Carlo integration are used to evaluate the four
      component Dirac equation for a number of one-electron atomic and diatomic
      systems. This combination produces accurate energies, is relatively simple to
      implement, and exhibits few of the problems associated with traditional
      techniques.

PMID- 11970153
TI  - Finite-volume lattice Boltzmann schemes in two and three dimensions.
AB  - Simple and practical finite-volume schemes for the lattice Boltzmann equation are
      derived in two and three dimensions through the application of modern finite
      volume methods. The schemes use a finite-volume vortex-type formulation based on
      quadrilateral elements in two dimensions and trilinear hexahedral elements in
      three dimensions. It is shown that the schemes are applicable to domains with
      irregular boundaries of arbitrary shape in two and three dimensions.

PMID- 11970154
TI  - Distributions of singular values for some random matrices.
AB  - The singular value decomposition is a matrix decomposition technique widely used
      in the analysis of multivariate data, such as complex space-time images obtained
      in both physical and biological systems. In this paper, we examine the
      distribution of singular values of low-rank matrices corrupted by additive noise.
      Past studies have been limited to uniform uncorrelated noise. Using diagrammatic
      and saddle point integration techniques, we extend these results to heterogeneous
      and correlated noise sources. We also provide perturbative estimates of error
      bars on the reconstructed low-rank matrix obtained by truncating a singular value
      decomposition.

PMID- 11970155
TI  - Asymmetric one-dimensional exclusion processes: a two-parameter exactly solvable
      example.
AB  - We consider a two-parameter family of asymmetric exclusion processes for
      particles living on a continuous one-dimensional space. Using the Bethe ansatz,
      the exact solution to the master equation, and from that the drift and the
      diffusion rate in the two particle sector, are obtained.

PMID- 11970156
TI  - Oscillatory behavior of critical amplitudes of the Gaussian model on a
      hierarchical structure.
AB  - We studied oscillatory behavior of critical amplitudes for the Gaussian model on
      a hierarchical structure presented by a modified Sierpinski gasket lattice. This
      model is known to display nonstandard critical behavior on the lattice under
      study. The leading singular behavior of the correlation length xi near the
      critical coupling K=K(c) is modulated by a function which is periodic in
      ln/ln(K(c)-K)/. We have also shown that the common finite-size scaling
      hypothesis, according to which for a finite system at criticality xi should be of
      the order of the size of the system, is not applicable in this case. As a
      consequence of this, the exact form of the leading singular behavior of xi
      differs from the one described earlier (which was based on the finite-size
      scaling assumption).

PMID- 11970157
TI  - Analytical verification of scaling laws for the Ising model with external field
      in fractal lattices.
AB  - We use an exact recursion procedure to verify analytically, without any
      intermediary numerical calculation, the validity of the hyperscaling (Josephson)
      law extended to fractals, the Rushbrooke and Griffiths scaling laws for the Ising
      ferromagnet with external magnetic field in the whole family of Migdal-Kadanoff
      like hierarchical lattices.

PMID- 11970158
TI  - Relation between the probability density and other properties of a stationary
      random process.
AB  - We consider the Pope-Ching differential equation [Phys. Fluids A 5, 1529 (1993)]
      connecting the probability density p(x)(x) of a stationary, homogeneous
      stochastic process x(t) and the conditional moments of its squared velocity and
      acceleration. We show that the solution of the Pope-Ching equation can be
      expressed as n(x)</v(x)/(-1)>, where n(x) is the mean number of crossings of the
      x level per unit time and </v(x)/(-1)> is the mean inverse velocity of crossing.
      This result shows that the probability density at x is fully determined by a one
      point measurement of crossing velocities, and does not imply knowledge of the
      x(t) behavior outside of the infinitesimally narrow window near x.

PMID- 11970159
TI  - Transition curves for the variance of the nearest neighbor spacing distribution
      for Poisson to Gaussian orthogonal and unitary ensemble transitions.
AB  - Using an appropriate 2x2 random matrix ensemble, transition curves for the
      variance of the nearest neighbor spacing distribution are constructed for the
      Poisson to Gaussian orthogonal and unitary ensemble transitions in terms of an
      easily identifiable transition parameter.

PMID- 11970160
TI  - Slow decay of the finite Reynolds number effect of turbulence.
AB  - The third-order structure function is used to study the finite Reynolds number
      (FRN) effect of turbulence, which refers to the deviation of turbulence
      statistics observed at finite Reynolds numbers from predictions of the Kolmogorov
      theories. It is found that the FRN effect decreases as CR(-mu)(lambda), when
      R(lambda) is high, and mu < or = 6/5. Here R(lambda) is the Taylor-microscale
      Reynolds number and C is a constant independent of R(lambda). From the exact
      spectral equations, the decay exponent mu and the constant C are determined for
      typical fully developed turbulent flows (freely decaying isotropic turbulence and
      shear flow turbulence), so that the quantitative prediction of the FRN effect is
      feasible.

PMID- 11970161
TI  - Hybrid weighted-density approximation for nonuniform fluid mixtures.
AB  - A hybrid weighted-density approximation (HWDA), which is based on both local
      density and globally averaged density, has been proposed to study the structural
      properties of nonuniform fluid mixtures. The advantage is that the HWDA is
      computationally much simpler than the extended weighted-density approximation
      proposed by Davidchack and Laird. The HWDA has been applied to calculate the
      density profiles of binary hard-sphere mixtures near a structureless hard wall.
      Comparison between the theoretical results and simulations for the confined
      binary hard-sphere mixtures demonstrates the reliable accuracy of the HWDA.

PMID- 11970162
TI  - Weighted-density approximation for general nonuniform fluid mixtures.
AB  - In order to construct a general density-functional theory for nonuniform fluid
      mixtures, we propose an extension to multicomponent systems of the weighted
      density approximation of Curtin and Ashcroft [Phys. Rev. A 32, 2909 (1985)]. This
      extension corrects a deficiency in a similar extension proposed earlier by Denton
      and Ashcroft [Phys. Rev. A 42, 7312 (1990)], in that that functional cannot be
      applied to the multicomponent nonuniform fluid systems with spatially varying
      composition, such as solid-fluid interfaces. As a test of the accuracy of our
      functional, we apply it to the calculation of the freezing phase diagram of a
      binary hard-sphere fluid, and compare the results to simulation and the Denton
      Ashcroft extension.

PMID- 11970163
TI  - Forbidden walls.
AB  - In this paper the presence of periodic twist-bend walls in the upper vicinity of
      the Freedericksz critical point of a nematic calamitic sample is reported.
      According to the existing theory, the formation of these structures could not
      happen in this region of the magnetic field. The length of the periodicity of
      these walls as well as the time spent with their formation have been measured,
      and it was demonstrated that the coherent motion of the nematic material cannot
      drive their construction. We assume that the mechanism responsible for their
      appearance results from the magnification of some selected random fluctuations
      occurring at the neighborhood of the Freedericksz critical point.

PMID- 11970164
TI  - Traveling time and traveling length in critical percolation clusters.
AB  - We study traveling time and traveling length for tracer dispersion in two
      dimensional bond percolation, modeling flow by tracer particles driven by a
      pressure difference between two points separated by Euclidean distance r. We find
      that the minimal traveling time t(min) scales as t(min) approximately r(1.33),
      which is different from the scaling of the most probable traveling time, t*
      approximately r(1.64). We also calculate the length of the path corresponding to
      the minimal traveling time and find l(min) approximately r(1.13) and that the
      most probable traveling length scales as l* approximately r(1.21). We present the
      relevant distribution functions and scaling relations.

PMID- 11970165
TI  - Entropic collapse transition of a polymer in a solvent with a nonadditive
      potential.
AB  - We use molecular dynamics simulations to study an entropy-driven collapse
      transition of a flexible polymer in a solvent. Monomers and solvent particles
      interact with a steeply repulsive soft-sphere potential. We consider a
      nonadditive potential system in which the effective diameter describing the
      solvent-monomer interaction is greater than or equal to the diameters
      corresponding to the solvent-solvent and monomer-monomer interactions, which are
      set equal. We examine the effects of nonadditivity of the solvent-monomer
      potential and solvent density on the collapse transition. We find that a small
      degree of nonadditivity will drive the transition at sufficiently high solvent
      density. Increasing the density leads to a collapse transition at lower values of
      nonadditivity.

PMID- 11970166
TI  - Mesoscopic theory of the viscoelasticity of polymers.
AB  - We have advanced our previous static theory of polymer entanglement involving an
      extended Cahn-Hilliard functional, to include time-dependent dynamics. We go
      beyond the Gaussian approximation, to the one-loop level, to compute the
      frequency dependent storage and loss moduli of the system. The four parameters in
      our theory are obtained by fitting to available experimental data on polystyrene
      melts of various chain lengths. This provides a physical representation of the
      parameters in terms of the chain length of the system. It is shown that the
      parameters chosen describe the crossover from an unentangled to an entangled
      state. The crossover is characterized by a dramatic increase in a time scale
      appearing in the theory, analogous to critical slowing down in phase transition
      theory. This result should stimulate more detailed experiments in this regime to
      test this concept.

PMID- 11970167
TI  - Hydrogen Balmer-alpha broadening in dense plasmas.
AB  - This work presents a theoretical analysis of experimental results for the
      hydrogen Balmer-alpha line in dense plasmas, with electron densities between
      2x10(18) and 9x10(18) e/cm(3) A simulation of both electrons and ions is employed
      to produce reliable theoretical widths. These results are essentially in
      agreement with standard theory results and, for the most part, disagree with the
      experimental results. Consequently, either mechanisms not accounted for in the
      theoretical results (such as quadrupoles) are more important than previously
      thought at these densities, or else there is a problem in the experimental data
      (such as a possible reabsorption, which is not ruled out by the experimental
      data).

PMID- 11970168
TI  - Hot-electron distribution functions in a subpicosecond laser interaction with
      solid targets of varying initial gradient scale lengths.
AB  - We have studied the distribution function of the hot electrons produced during
      the interaction of a 120-fs, 60-mJ, 800-nm wavelength and a p-polarized laser
      pulse with bilayered Al/Fe targets. The main pulse interacts with a preformed
      plasma, obtained with a controlled prepulse, whose density gradient scale length
      has been measured. The electron distribution function is characterized by means
      of the Kalpha emission of the two materials of the target as a function of the Al
      layer thickness. The low-energy region (<50 keV) of the hot-electron distribution
      function shows no dependency in shape on the gradient scale length, but only a
      variation in the total number of the generated electrons. The comparison between
      the experimental results and the particle-in-cell and Monte Carlo calculations of
      the electron distribution function and the Kalpha emission is gratifying.

PMID- 11970169
TI  - Comment on "Quantum processes in the field of a two-frequency circularly
      polarized plane electromagnetic wave".
AB  - We show that there is a mistake in the results recently published by An Yu and H.
      Takahashi [Phys. Rev. E 57, 2276 (1998)] for the probabilities of a photon
      emission by an electron and a pair production by a photon in the field of a two
      frequency plane electromagnetic wave. In this paper we present the corrected
      expression for the probability of a photon emission which contains terms missed
      by Yu and Takahashi. We argue also that the effect of presence of the waves with
      combination frequencies in the external field proposed by the authors of the
      paper [Phys. Rev. E 57, 2276 (1998)] has no physical basis.

PMID- 11970170
TI  - Persistence in systems with algebraic interaction.
AB  - Persistence in coarsening one-dimensional spin systems with a power-law
      interaction r(-1-sigma) is considered. Numerical studies indicate that for
      sufficiently large values of the interaction exponent sigma (sigma > or =1/2 in
      our simulations), persistence decays as an algebraic function of the length scale
      L, P(L) approximately L(-theta). The persistence exponent theta is found to be
      independent on the force exponent sigma and close to its value for the extremal
      (sigma-->infinity) model, theta =0.175 075 88. For smaller values of the force
      exponent (sigma < 1/2), finite size effects prevent the system from reaching the
      asymptotic regime. Scaling arguments suggest that in order to avoid significant
      boundary effects for small sigma, the system size should grow as
      [O(1/sigma)](1/sigma).

PMID- 11970171
TI  - Reweighting in nonequilibrium simulations.
AB  - A simple reweighting scheme is proposed for Monte Carlo simulations of
      interacting particle systems, permitting one to study various parameter values in
      a single study, and improving efficiency by an order of magnitude. Unlike earlier
      reweighting schemes, the present approach does not require knowledge of the
      stationary probability distribution, and so is applicable out of equilibrium. The
      method is applied to the contact process in two and three dimensions, yielding
      the critical parameter and spreading exponents to unprecedented precision.

PMID- 11970172
TI  - Persistence in the zero-temperature dynamics of the diluted Ising ferromagnet in
      two dimensions.
AB  - The nonequilibrium dynamics of the strongly diluted random-bond Ising model in
      two dimensions (2D) is investigated numerically. The persistence probability,
      P(t), of spins which do not flip by time t is found to decay to a nonzero,
      dilution-dependent value P(infinity). We find that p(t)=P(t)-P(infinity) decays
      exponentially to zero at large times. Furthermore, the fraction of spins which
      never flip is a monotonically increasing function over the range of bond-dilution
      considered. Our findings, which are consistent with a recent result of Newman and
      Stein [Phys. Rev. Lett. 82, 3944 (1999)], suggest that persistence in diluted and
      pure systems falls into different classes. Furthermore, its behavior would also
      appear to depend crucially on the strength of the dilution present.

PMID- 11970173
TI  - Optimal paths in disordered media: scaling of the crossover from self-similar to
      self-affine behavior.
AB  - We study optimal paths in disordered energy landscapes using energy distributions
      of the type P(log(10) E)=const that lead to the strong disorder limit. If we
      truncate the distribution, so that P(log(10) E)=const only for E(min) < or =E <
      or =E(max), and P(log(10) E)=0 otherwise, we obtain a crossover from self-similar
      (strong disorder) to self-affine (moderate disorder) behavior at a path length
      l(x). We find that l(x) proportional, variant[log(10)(E(max)/E(min))](kappa),
      where the exponent kappa has the value kappa=1.60 +/- 0.03 both in d=2 and d=3.
      We show how the crossover can be understood from the distribution of local
      energies on the optimal paths.

PMID- 11970174
TI  - Power fluctuations in a closed turbulent shear flow.
AB  - We study experimentally the power consumption P of a confined turbulent flow at
      constant Reynolds number Re. We analyze in details its temporal dynamics and
      statistical properties, in a setup that covers two decades in Reynolds numbers.
      We show that nontrivial power fluctuations occur over a wide range of amplitudes
      and that they involve coherent fluid motions over the entire system size. As a
      result, the power fluctuations do not result from averaging of independent
      subsystems and its probability density function Pi(P) is strongly non-Gaussian.
      The shape of Pi(P) is Reynolds number independant and we show that the relative
      intensity of fluctuations decreases very slowly as Re increases. These results
      are discussed in terms of an analogy with critical phenomena.

PMID- 11970175
TI  - Thinning transitions in free-standing liquid-crystal films as the successive
      formation of dislocation loops.
AB  - We describe a model for the layer-thinning transition in free-standing liquid
      crystal films based on the successive, spontaneous formation of dislocation
      loops. As the film temperature increases and the smectic order and layer
      compressional modulus decrease, the condition for creating a dislocation loop of
      critical radius is met and a thinning is nucleated. The resulting equation for N,
      the number of smectic layers, as a function of temperature yields good fitting
      results to the thinning transitions obtained from several fluorinated compounds.

PMID- 11970176
TI  - Competition between glassiness and order in a multispin glass.
AB  - A mean-field multispin interaction spin glass model is analyzed in the presence
      of a ferromagnetic coupling. The static and dynamical phase diagrams contain four
      phases (paramagnet, spin glass, ordinary ferromagnet, and glassy ferromagnet) and
      exhibit reentrant behavior. The glassy ferromagnet phase has anomalous dynamical
      properties. The results are consistent with a nonequilibrium thermodynamics that
      has been proposed for glasses.

PMID- 11970178
TI  - Velocity distributions and density fluctuations in a granular gas.
AB  - Velocity distributions in a vibrated granular monolayer are investigated
      experimentally. Non-Gaussian velocity distributions are observed at low vibration
      amplitudes but cross over smoothly to Gaussian distributions as the amplitude is
      increased. Cross-correlations between fluctuations in density and temperature are
      present only when the velocity distributions are strongly non-Gaussian. Confining
      the expansion of the granular layer results in non-Gaussian velocity
      distributions that persist to high vibration amplitudes.

PMID- 11970177
TI  - Brillouin and Umklapp scattering in polybutadiene: comparison of neutron and x
      ray scattering.
AB  - We report a comparison of high resolution inelastic x-ray Brillouin scattering to
      coherent inelastic neutron scattering for amorphous deuterated polybutadiene,
      done for one temperature in the glass phase and another one in the melt. The x
      ray scattering proves to be by far the better technique for such a polymer within
      its present resolution bounds. The neutron scattering allows one to extend these
      measurements to a much better resolution, showing an additional quasielastic
      signal in the melt. The results suggest x-ray measurements at higher momentum
      transfer, to see whether they are complementary to neutrons.

PMID- 11970179
TI  - Adsorption phenomena in amphiphilic systems.
AB  - The wetting behavior of a ternary mixture of oil, water, and amphiphile in the
      presence of a surface is studied. An interface model carefully derived from an
      underlying Ginzburg-Landau theory is introduced, which contains position
      dependent rigidity and stiffness coefficients. Using this model we predict a rich
      surface phase diagram containing thin-thick, first-order, and continuous wetting
      transitions. Application of the model to other interface behavior in these
      mixtures is also addressed.

PMID- 11970181
TI  - Advance in diagnostics for high-temperature plasmas based on the analytical
      result for the ion dynamical broadening of hydrogen spectral lines.
AB  - It is well known that the ion dynamics is very important for Stark broadening of
      spectral lines in high-T plasmas. However, it is usually assumed that with the
      increase of the plasma density N and/or of the principal quantum number n of the
      upper level of the radiator, the ionic contribution to the impact width (ICIW)
      tends to zero. In distinction to that paradigm, by finding an analytical result
      for the ion dynamical broadening of hydrogen spectral lines, we show here that
      with the increase of N and/or n, the ICIW does not decrease. Moreover, for
      practically important ranges of T, N, and n, this "residual" ICIW, being
      virtually independent of n, can be comparable to the standard electron impact
      width. This result leads to: (i) a substantial revision of the past of diagnostic
      conclusions for a variety of high-T plasma experiments; (ii) a much better
      possibility to deduce from experimental, Stark-broadened line profiles not only
      the plasma density but also the plasma temperature; (iii) a significant
      enhancement of the accuracy of N and T obtained from experimental line profiles;
      and (iv) a substantial revision of simulation models for the ion dynamical
      contribution that were based on a wrong assumption that the latter vanishes under
      increasing N and/or n. The consequences are especially important for tokamak
      plasmas, where the diagnostics based on experimental profiles of high Balmer and
      Paschen lines is frequently used.

PMID- 11970180
TI  - Neutron scattering evidence of a boson peak in protein hydration water.
AB  - Measurement of the low temperature neutron excess of scattering of H2O-hydrated
      plastocyanin relative to D2O-hydrated protein allowed us to reveal the presence
      of an inelastic peak at about 3.5 meV. This excess of vibrational modes,
      elsewhere termed "boson peak," is due to the dynamical behavior of the water
      molecules belonging to the H2O-hydration shell surrounding the protein. The
      relevance of the boson peak to the dynamical coupling between the solvent and the
      protein, and hence to the protein functionality is addressed.

PMID- 11970182
TI  - Response function including collisions for an interacting fermion gas.
AB  - The response function of an interacting fermion gas is considered in the entire
      (k-->,omega) space. Applying a generalized linear response theory, it is
      expressed in terms of determinants of equilibrium correlation functions, which
      allow for a systematic perturbative treatment. The relation to dynamical local
      field factors is given. As a special case, the dielectric function is evaluated
      for two-component (hydrogen) plasmas at arbitrary degeneracies. Collisions are
      treated in Born approximation leading to a (k-->,omega)-dependent collision
      integral. The link to the dynamical conductivity is given in the long-wavelength
      limit. Sum rules are discussed.

PMID- 11970183
TI  - Chirped pulse reflectivity and frequency domain interferometry in laser driven
      shock experiments.
AB  - We show the simultaneous applicability of the frequency domain interferometry and
      the chirped pulse reflectometry techniques to measure shock parameters. The
      experiment has been realized with the laser at the Laboratoire pour l'Utilisation
      des Lasers Intenses (LULI) with a 550-ps pulse duration and an intensity on
      target approximately 5 x 10(13) W/cm(2) to produce a shock in a layered aluminum
      fused silica target. A second low energy, partially compressed chirped probe beam
      was used to irradiate the target rear side and the reflected light has been
      analyzed with a spectrometer, achieving a temporal resolution of the order of 1
      ps.

PMID- 11970184
TI  - Nonlinear model of intramolecular excitations on a multileg ladder lattice.
AB  - The exactly integrable model of nonlinear intramolecular excitations on a
      multileg ladder lattice is proposed. Since it is rather general, the model
      permits a number of physically interesting ramifications related to the striplike
      and the bunchlike biological and condensed matter systems as well as to the
      arrays of linearly and nonlinearly coupled optical fibers. The principal
      possibility to model an external magnetic field parallel to the ladder legs
      within the framework of inverse scattering transform is pointed out. The one
      soliton solutions of two-leg and three-leg ladder models are found and analyzed.
      Apart from the spatially constricted translational mode typical to the
      traditional one-chain soliton, the interchain beating mode as well as the
      circular traveling modes redistributing the excitations between the chains are
      revealed in complete accordance with liner limits.

PMID- 11970185
TI  - Ground-state degeneracy of Potts antiferromagnets on two-dimensional lattices:
      approach using infinite cyclic strip graphs.
AB  - The q-state Potts antiferromagnet on a lattice Lambda exhibits nonzero ground
      state entropy S0=kB ln W for sufficiently large q and hence is an exception to
      the third law of thermodynamics. An outstanding challenge has been the
      calculation of W(sq,q) on the square (sq) lattice. We present here an exact
      calculation of W on an infinite-length cyclic strip of the square lattice, which
      embodies the expected analytic properties of W(sq,q). Similar results are given
      for the kagome lattice.

PMID- 11970186
TI  - Transport on an annealed disordered lattice.
AB  - We study the diffusion on an annealed disordered lattice with a local dynamical
      reorganization of bonds. We show that the typical rearrangement time depends on
      the renewal rate like tr approximately tau(alpha) with alpha not equal 1. This
      implies that the crossover time to normal diffusion in a slow rearrangement
      regime shows a critical behavior at the percolation threshold. Additional scaling
      relations for the dependence of the diffusion coefficient on the renewal rate are
      obtained. The derivation of scaling exponents confirms the crucial role of singly
      connected bonds in transport properties. These results are checked by numerical
      simulations in two and three dimensions.

PMID- 11970187
TI  - Pauli paramagnetic gas in the framework of Riemannian geometry.
AB  - We investigate the thermodynamic curvature resulting from a Riemannian geometry
      approach to thermodynamics for the Pauli paramagnetic gas which is a system of
      identical fermions each with spin 1 / 2, and also for classical ideal
      paramagnetic gas. We find that both the curvature of classical ideal paramagnetic
      gas and the curvature of the Pauli gas in the classical limit reduce to that of a
      two-component ideal gas. On the other hand, it is seen straightforwardly that the
      curvature of classical gas satisfies the geometrical equation exactly. Also a
      simple relationship between the curvature of Pauli gas and the correlation volume
      is obtained. We see that it is only in the classical and semiclassical regime
      that the absolute value of the thermodynamic curvature can be interpreted as a
      measure of the stability of the system.

PMID- 11970188
TI  - Improved high-temperature expansion and critical equation of state of three
      dimensional Ising-like systems.
AB  - High-temperature series are computed for a generalized three-dimensional Ising
      model with arbitrary potential. Three specific "improved" potentials (suppressing
      leading scaling corrections) are selected by Monte Carlo computation. Critical
      exponents are extracted from high-temperature series specialized to improved
      potentials, achieving high accuracy; our best estimates are gamma=1.2371(4),
      nu=0.630 02(23), alpha=0.1099(7), eta=0.0364(4), beta=0.326 48(18). By the same
      technique, the coefficients of the small-field expansion for the effective
      potential (Helmholtz free energy) are computed. These results are applied to the
      construction of parametric representations of the critical equation of state. A
      systematic approximation scheme, based on a global stationarity condition, is
      introduced (the lowest-order approximation reproduces the linear parametric
      model). This scheme is used for an accurate determination of universal ratios of
      amplitudes. A comparison with other theoretical and experimental determinations
      of universal quantities is presented.

PMID- 11970189
TI  - Coarsening kinetics from a variable-mobility Cahn-Hilliard equation: application
      of a semi-implicit Fourier spectral method.
AB  - An efficient semi-implicit Fourier spectral method is implemented to solve the
      Cahn-Hilliard equation with a variable mobility. The method is orders of
      magnitude more efficient than the conventional forward Euler finite-difference
      method, thus allowing us to simulate large systems for longer times. We studied
      the coarsening kinetics of interconnected two-phase mixtures using a Cahn
      Hilliard equation with its mobility depending on local compositions. In
      particular, we compared the kinetics of bulk-diffusion-dominated and interface
      diffusion-dominated coarsening in two-phase systems. Results are compared with
      existing theories and previous computer simulations.

PMID- 11970190
TI  - Simplified replica treatment of various random-energy and random-field models
      with confinement potential.
AB  - A modified version of the replica method recently proposed by the authors [J.
      Phys. A 32, 585 (1999)] is applied to a certain class of models describing the
      motion of a particle in a random potential with superposed parabolic confinement.
      Different types of randomness are considered. Previous treatments of analogous
      models were based on replica symmetry breaking (RSB). The aim of the paper is to
      demonstrate that the new method provides reliable results for the average free
      energy and related quantities without taking into account RSB. The comparison
      with computer simulations shows satisfactory agreement.

PMID- 11970191
TI  - Spectral statistics and dynamics of Levy matrices.
AB  - We study the spectral statistics and dynamics of a random matrix model where
      matrix elements are taken from power-law tailed distributions. Such
      distributions, labeled by a parameter mu, converge on the Levy basin, giving the
      matrix model the label "Levy matrix" [P. Cizeau and J. P. Bouchaud, Phys. Rev. E
      50, 1810 (1994)]. Such matrices are interesting because their properties go
      beyond the Gaussian universality class and they model many physically relevant
      systems such as spin glasses with dipolar or Ruderman-Kittel-Kasuya-Yosida
      interactions, electronic systems with power-law decaying interactions, and the
      spectral behavior at the metal insulator transition. Regarding the density of
      states we extend previous work to reveal the sparse matrix limit as mu-->0.
      Furthermore, we find for 2 x 2 Levy matrices that geometrical level repulsion is
      not affected by the distribution's broadness. Nevertheless, essential
      singularities particular to Levy distributions for small arguments break
      geometrical repulsion and make it mu dependent. Level dynamics as a function of a
      symmetry breaking parameter gives new insight into the phases found by Cizeau and
      Bouchaud (CB). We map the phase diagram drawn qualitatively by CB by using the
      delta3 statistic. Finally we compute the conductance of each phase by using the
      Thouless formula, and find that the mixed phase separating conducting and
      insulating phases has a unique character.

PMID- 11970192
TI  - Constructing new periodic exact solutions of evolution equations.
AB  - For the nonlinear Schrodinger equation, the Korteweg-de Vries equation, and the
      modified Korteweg-de Vries equation, periodic exact solutions are constructed
      from their stationary periodic solutions, by means of the Backlund
      transformation. These periodic solutions were not written down explicitly before
      to our knowledge. Their asymptotic behavior when t-->-infinity is different from
      that when t-->infinity. Near t=0, the spatial-temporal pattern can change
      abruptly, and rational solitons can appear randomly in space and time. They
      correspond to new types of "homoclinic orbits" due to different asymptotic
      behaviors in time.

PMID- 11970193
TI  - Noise-induced phase separation: mean-field results.
AB  - We present a study of a phase-separation process induced by the presence of
      spatially correlated multiplicative noise. We develop a mean-field approach
      suitable for conserved-order-parameter systems and use it to obtain the phase
      diagram of the model. Mean-field results are compared with numerical simulations
      of the complete model in two dimensions. Additionally, a comparison between the
      noise-driven dynamics of conserved and nonconserved systems is made at the level
      of the mean-field approximation.

PMID- 11970194
TI  - Domain-wall free energy of spin-glass models: numerical method and boundary
      conditions.
AB  - An efficient Monte Carlo method is extended to evaluate directly domain-wall free
      energy for randomly frustrated spin systems. Using the method, critical phenomena
      of spin-glass phase transition are investigated in the 4d+/-J Ising model under
      the replica boundary condition. Our values of the critical temperature and
      exponent, obtained by finite-size scaling, are in good agreement with those of
      the standard Monte Carlo and the series expansion studies. In addition, two
      exponents, the stiffness exponent and the fractal dimension of the domain wall,
      which characterize the ordered phase, are obtained. The latter value is larger
      than d-1, indicating that the domain wall is really rough in the 4d Ising spin
      glass phase.

PMID- 11970195
TI  - Phase-field model of dendritic sidebranching with thermal noise.
AB  - We investigate dendritic sidebranching during crystal growth in an undercooled
      melt by simulation of a phase-field model which incorporates thermal noise of
      microscopic origin. As a nontrivial quantitative test of this model, we first
      show that the simulated fluctuation spectrum of a one-dimensional interface in
      thermal equilibrium agrees with the exact sharp-interface spectrum up to an
      irrelevant short-wavelength cutoff comparable to the interface thickness.
      Simulations of dendritic growth are then carried out in two dimensions to compute
      sidebranching characteristics (root-mean-square amplitude and sidebranch spacing)
      as a function of distance behind the tip. These quantities are compared
      quantitatively to the predictions of the existing linear WKB theory of noise
      amplification. The extension of this study to three dimensions remains needed to
      determine the origin of noise in experiments.

PMID- 11970196
TI  - Pattern selection in a lattice of pulse-coupled oscillators.
AB  - We study spatio-temporal pattern formation in a ring of N oscillators with
      inhibitory unidirectional pulselike interactions. The attractors of the dynamics
      are limit cycles where each oscillator fires once and only once. Since some of
      these limit cycles lead to the same pattern, we introduce the concept of pattern
      degeneracy to take it into account. Moreover, we give a qualitative estimation of
      the volume of the basin of attraction of each pattern by means of some
      probabilistic arguments and pattern degeneracy, and show how they are modified as
      we change the value of the coupling strength. In the limit of small coupling, our
      estimative formula gives a perfect agreement with numerical simulations.

PMID- 11970197
TI  - Statistical mechanics of self-driven Carnot cycles.
AB  - The spontaneous generation and finite-amplitude saturation of sound, in a
      traveling-wave thermoacoustic engine, are derived as properties of a second-order
      phase transition. It has previously been argued that this dynamical phase
      transition, called "onset," has an equivalent equilibrium representation, but the
      saturation mechanism and scaling were not computed. In this work, the sound modes
      implementing the engine cycle are coarse-grained and statistically averaged, in a
      partition function derived from microscopic dynamics on criteria of scale
      invariance. Self-amplification performed by the engine cycle is introduced
      through higher-order modal interactions. Stationary points and fluctuations of
      the resulting phenomenological Lagrangian are analyzed and related to background
      dynamical currents. The scaling of the stable sound amplitude near the critical
      point is derived and shown to arise universally from the interaction of finite
      temperature disorder, with the order induced by self-amplification.

PMID- 11970198
TI  - Damage spreading transition in glasses: a probe for the ruggedness of the
      configurational landscape.
AB  - We consider damage spreading transitions in the framework of mode-coupling
      theory. This theory describes relaxation processes in glasses in the mean-field
      approximation which are known to be characterized by the presence of an
      exponentially large number of metastable states. For systems evolving under
      identical but arbitrarily correlated noises, we demonstrate that there exists a
      critical temperature T0 which separates two different dynamical regimes depending
      on whether damage spreads or not in the asymptotic long-time limit. This
      transition exists for generic noise correlations such that the zero damage
      solution is stable at high temperatures, being minimal for maximal noise
      correlations. Although this dynamical transition depends on the type of noise
      correlations, we show that the asymptotic damage has the good properties of a
      dynamical order parameter, such as (i) independence of the initial damage; (ii)
      independence of the class of initial condition; and (iii) stability of the
      transition in the presence of asymmetric interactions which violate detailed
      balance. For maximally correlated noises we suggest that damage spreading occurs
      due to the presence of a divergent number of saddle points (as well as metastable
      states) in the thermodynamic limit consequence of the ruggedness of the free
      energy landscape which characterizes the glassy state. These results are then
      compared to extensive numerical simulations of a mean-field glass model (the
      Bernasconi model) with Monte Carlo heat-bath dynamics. The freedom of choosing
      arbitrary noise correlations for Langevin dynamics makes damage spreading an
      interesting tool to probe the ruggedness of the configurational landscape.

PMID- 11970199
TI  - Universal behavior in an irreversible model with C(3v) symmetry.
AB  - We analyze the critical behavior of a two-dimensional irreversible cellular
      automaton whose dynamic rules are invariant under the symmetry operations of the
      point group C3v. We study the dynamical phase transition that takes place in the
      model and obtain the static and short-time critical exponents by the use of Monte
      Carlo simulations. Our results indicate that the present model is in the same
      universality class as the three-state Potts model.

PMID- 11970200
TI  - Geometry of fully coordinated, two-dimensional percolation.
AB  - We study the geometry of the critical clusters in fully coordinated percolation
      on the square lattice. By Monte Carlo simulations (static exponents) and normal
      mode analysis (dynamic exponents), we find that this problem is in the same
      universality class with ordinary percolation statically but not so dynamically.
      We show that there are large differences in the number and distribution of the
      interior sites between the two problems that may account for the different
      dynamic nature.

PMID- 11970201
TI  - Energy distribution of the quantum harmonic oscillator under random time
      dependent perturbations.
AB  - This paper investigates the evolution of a quantum particle in a harmonic
      oscillator driven by time-dependent forces. The perturbations are small, but they
      act long enough so that we can solve the problem in the asymptotic framework
      corresponding to a perturbation amplitude that tends to zero and a perturbation
      duration that tends to infinity. We describe the effective evolution equation of
      the state vector, which reads as a stochastic partial differential equation. We
      exhibit a closed-form equation for the transition probabilities, which can be
      interpreted in terms of a jump process. Using standard probability tools, we are
      then able to compute explicitly the probabilities for observing the different
      energy eigenstates and give the exact statistical distribution of the energy of
      the particle.

PMID- 11970202
TI  - Renormalization group for renormalization-group equations toward the universality
      classification of infinite-order phase transitions.
AB  - We derive a renormalization group to calculate the nontrivial critical exponent
      of the divergent correlation length, thereby providing a universality
      classification of essential singularities in infinite-order phase transitions.
      This method thus resolves the vanishing scaling matrix problem. The exponent is
      obtained from the maximal eigenvalue of a scaling matrix in this renormalization
      group, as in the case of ordinary second-order phase transitions. We exhibit
      several nontrivial universality classes in infinite-order transitions different
      from the well known Berezinskii-Kosterlitz-Thouless transition.

PMID- 11970203
TI  - Structural relaxation in atomic clusters: master equation dynamics.
AB  - The role of the potential energy landscape in determining the relaxation dynamics
      of model clusters is studied using a master equation. Two types of energy
      landscape are examined: a single funnel, as exemplified by 13-atom Morse
      clusters, and the double funnel landscape of the 38-atom Lennard-Jones cluster.
      Interwell rate constants are calculated using Rice-Ramsperger-Kassel-Marcus
      theory within the harmonic approximation, but anharmonic model partition
      functions are also considered. Decreasing the range of the potential in the Morse
      clusters is shown to hinder relaxation toward the global minimum, and this effect
      is related to the concomitant changes in the energy landscape. The relaxation
      modes that emerge from the master equation are interpreted and analyzed to
      extract interfunnel rate constants for the Lennard-Jones cluster. Since this
      system is too large for a complete characterization of the energy landscape, the
      conditions under which the master equation can be applied to a limited database
      are explored. Connections are made to relaxation processes in proteins and
      structural glasses.

PMID- 11970204
TI  - Renormalization-group study of one-dimensional systems with roughening
      transitions.
AB  - A recently introduced real-space renormalization-group technique, developed for
      the analysis of processes in the Kardar-Parisi-Zhang universality class, is
      generalized and tested by applying it to a different family of surface-growth
      processes. In particular, we consider a growth model exhibiting a rich
      phenomenology even in one dimension. It has four different phases and a directed
      percolation-related roughening transition. The renormalization method reproduces
      extremely well all of the phase diagram, the roughness exponents in all the
      phases, and the separatrix among them. This proves the versatility of the method
      and elucidates interesting physical mechanisms.

PMID- 11970205
TI  - Steady-state currents in sharp stochastic ratchets.
AB  - We develop and analyze a model for particle transport in a stochastic ratchet
      with a periodic piecewise linear potential, with diffusion coefficient D, where
      the force is discontinuous in position and fluctuating in time via additive
      telegraph noise with correlation time tau. We find asymptotic formulas for the
      steady-state particle current J for large and small D and tau. For example, for
      small tau, the sharp corners in the potential lead to J=O(tau(2) exp[-(Dtau)(
      1/2)])+O(tau(5/2)), in contrast to O(tau(3)) when the potential is smooth. We
      show that diffusion can increase or decrease J, and derive an approximate
      equation for the value of D that maximizes J.

PMID- 11970206
TI  - Electromigration-induced soliton propagation on metal surfaces.
AB  - It is demonstrated that under certain conditions, solitons can propagate on the
      surface of a current-carrying metal thin film. The equation of motion for small
      amplitude, long waves is the Korteweg-de Vries equation in the limit of high
      applied currents. The solitons are protrusions whose velocity decreases linearly
      with amplitude and that propagate in the direction of the applied electric field.

PMID- 11970207
TI  - Black-eye patterns: a representation of three-dimensional symmetries in thin
      domains.
AB  - What is believed to be the first experimental evidence for Turing patterns was
      observed in the CIMA reaction by De Kepper and colleagues. Ouyang and Swinney
      performed further experiments in a "thin" layer of gel. Patterns observed at
      onset were basically two-dimensional. However, beyond onset a structure that does
      not typically occur in two-dimensional domains was observed-the black-eye
      pattern. In this paper we use the full three-dimensionality of the patterned
      layer to find a setting where black-eye patterns naturally occur. We propose that
      black-eye patterns have the symmetry of a body-centered-cubic lattice.

PMID- 11970208
TI  - Critical-point finite-size scaling in the microcanonical ensemble.
AB  - We develop a scaling theory for the finite-size critical behavior of the
      microcanonical entropy (density of states) of a system with a critically
      divergent heat capacity. The link between the microcanonical entropy and the
      canonical energy distribution is exploited to establish the former, and
      corroborate its predicted scaling form, in the case of the 3d Ising universality
      class. We show that the scaling behavior emerges clearly when one accounts for
      the effects of the negative background constant contribution to the canonical
      critical specific heat. We show that this same constant plays a significant role
      in determining the observed differences between the canonical and microcanonical
      specific heats of systems of finite size, in the critical region.

PMID- 11970209
TI  - Ground-state degeneracies of Ising spin glasses on diamond hierarchical lattices.
AB  - The total number of ground states for short-range Ising spin glasses, defined on
      diamond hierarchical lattices of fractal dimensions d=2, 3, 4, 5, and 2.58, is
      estimated by means of analytic calculations (three last hierarchy levels of the
      d=2 lattice) and numerical simulations (lower hierarchies for d=2 and all
      remaining cases). It is shown that in the case of continuous probability
      distributions for the couplings, the number of ground states is finite in the
      thermodynamic limit. However, for a bimodal probability distribution (+/-J with
      probabilities p and 1-p, respectively), the average number of ground states is
      maximum for a wide range of values of p around p=1 / 2 and depends on the total
      number of sites at hierarchy level n, Nn. In this case, for all lattices
      investigated, it is shown that the ground-state degeneracy behaves like
      exp[h(d)Nn], in the limit Nn large, where h(d) is a positive number which depends
      on the lattice fractal dimension. The probability of finding frustrated cells at
      a given hierarchy level n, Fn(p), is calculated analytically (three last
      hierarchy levels for d=2 and the last hierarchy of the d=3 lattice, with
      0<or=p<or=1), as well as numerically (all other cases, with p=1 / 2). Except for
      d=2, in which case Fn(1 / 2) increases by decreasing the hierarchy level, all
      other dimensions investigated present an exponential decrease in Fn(1 / 2) for
      decreasing values of n. For d=2 our results refer to the paramagnetic phase,
      whereas for all other dimensions considered [which are greater than the lower
      critical dimension dl (dl approximately 2.5)], our results refer to the spin
      glass phase at zero temperature; in the latter cases h(d) increases with the
      fractal dimension. For n>>1, only the last hierarchies contribute significantly
      to the ground-state degeneracy; such a dominant behavior becomes stronger for
      high fractal dimensions. The exponential increase of the number of ground states
      with the total number of sites is in agreement with the mean-field picture of
      spin glasses.

PMID- 11970210
TI  - Asymmetry and direction reversal in fluctuation-induced biased Brownian motion.
AB  - The biased movement of a Brownian particle in a periodic potential fluctuating
      between a flat and a kinked ratchet state, as first studied by Chauwin, Ajdari,
      and Prost, is examined. The purpose is to study the physical origin of the
      frequency-dependent direction reversal of the biased Brownian motion in this
      system. We show that the existence of the directional reversal depends not only
      on the lengths of the projections of the two ratchet arms on the potential axis
      (the arm-projection asymmetry), but also the overall spatial geometry of the
      potential in a period. In particular, we show that the direction reversal can be
      obtained in this kinked ratchet model even when the two arm projections are
      equal. Since this two-state model is the simplest to generate direction reversal
      and particles can be separated more efficiently in a fluctuating potential if
      direction reversal exists, the results obtained in this study should be useful
      for future application in particle separation.

PMID- 11970211
TI  - Vortex dynamics in a three-state model under cyclic dominance.
AB  - The evolution of domain structure is investigated in a two-dimensional voter
      model with three states under cyclic dominance. The study focus on the dynamics
      of vortices, defined by the points where the three states (domains) meet. We can
      distinguish vortices and antivortices which walk randomly and annihilate each
      other. The domain wall motion can create vortex-antivortex pairs at a rate that
      is increased by the spiral formation due to cyclic dominance. This mechanism is
      contrasted with a branching annihilating random walk (BARW) in a particle
      antiparticle system with density-dependent pair creation rate. Numerical
      estimates for the critical indices of the vortex density [beta=0.29(4)] and of
      its fluctuation [gamma=0.34(6)] improve an earlier Monte Carlo study [K. Tainaka
      and Y. Itoh, Europhys. Lett. 15, 399 (1991)] of the three-state cyclic model in
      two dimensions.

PMID- 11970212
TI  - Finite times to equipartition in the thermodynamic limit.
AB  - We study the time scale T to equipartition in a 1D lattice of N masses coupled by
      quartic nonlinear (hard) springs (the Fermi-Pasta-Ulam beta model). We take the
      initial energy to be either in a single mode gamma or in a package of low
      frequency modes centered at gamma and of width deltagamma, with both gamma and
      deltagamma proportional to N. These initial conditions both give, for finite
      energy densities E/N, a scaling in the thermodynamic limit (large N), of a finite
      time to equipartition which is inversely proportional to the central mode
      frequency times a power of the energy density (E/N). A theory of the scaling with
      (E/N) is presented and compared to the numerical results in the range
      0.03<or=E/N<or=0.8.

PMID- 11970213
TI  - Stationary states of Toom cellular automata in simulations.
AB  - Stationary states of Toom probabilistic cellular automata are tested in computer
      experiments. The aim of the tests is to identify the features characterizing the
      equilibrium states understood as in statistical mechanics. Namely, we investigate
      the following: scaling laws that involve critical parameters beta, gamma, and nu,
      locality of the interactions, and density of the relative entropy between
      stationary states. The arguments showing that stationary Toom states are not the
      equilibrium ones are provided.

PMID- 11970214
TI  - Reaction-controlled cooperative desorption in a one-dimensional lattice: a
      dynamical approach.
AB  - The spinlike dynamics of immobile reactants in a one-dimensional lattice is
      analyzed for two representative systems involving cooperative desorption. An
      exact combinatorial approach is worked out. Its failure to reproduce the results
      of microscopic simulations is shown to be associated with the lack of
      sufficiently strong ergodic properties, as a result of which the final state
      depends strongly on the initial conditions. A dynamical approach to the problem
      based on the Master equation description is subsequently developed, leading to
      full agreement with the microscopic simulations.

PMID- 11970215
TI  - Self-similar renormalization approach to barrier crossing processes.
AB  - An algebraic self-similar renormalization method developed recently for summation
      of divergent field-theoretical series is applied to the thermally activated
      escape of a Brownian particle over an arbitrarily shaped barrier. Based on the
      Mel'nikov-Meshkov result for the underdamped Brownian motion and the inverse
      friction expansion of the underlying Fokker-Planck equation for strong friction,
      an overall rate formula is constructed. This formula agrees in the weak friction
      regime with the rate obtained from a diffusion equation in energy variables and,
      in the limiting case of strong friction with the rate following from a
      Smoluchowski equation. Its validity is tested for Brownian motion in bistable
      potentials with parabolic, cusped, and quartic barriers of different heights. The
      proposed formula is found to give a reasonable description of activated rate
      processes even though the barrier is quite low. Our comparison also includes
      results from various different crossover theories. In most of the cases
      considered the present formula is in considerably better agreement with exact
      numerical rates than the other interpolation formulas.

PMID- 11970216
TI  - Density dependence of vibrational energy relaxation rates in supercritical
      solution: a hydrodynamic model.
AB  - An approximate expression describing the density dependence of vibrational energy
      relaxation rates in fluids in terms of thermodynamic and transport parameters of
      the fluid is developed on the basis of a classical statistical mechanical theory
      of vibrational energy relaxation of highly excited molecules in polyatomic
      solvents. The energy relaxation rate is expressed via the friction coefficient,
      which describes the interaction between solute oscillator and solvent molecules.
      The corresponding force-force time correlation function is expressed in terms of
      the dynamic structure factor of the solvent and the force of interaction between
      solute and solvent molecules. Approximating the dynamic structure factor
      appropriately leads to expressions for the density dependence of vibrational
      relaxation rates in terms of thermophysical solvent parameters. Using these
      expressions the density dependence of vibrational relaxation rates in
      supercritical ethane and propane both in the vicinity of the critical point and
      far from it are evaluated and compared with measured relaxation rates obtained
      under the same physical conditions.

PMID- 11970217
TI  - Critical behavior of the two-dimensional spin-diluted Ising model via the
      equilibrium ensemble approach.
AB  - The equilibrium ensemble approach to disordered systems is used to investigate
      the critical behavior of the two-dimensional Ising model in the presence of
      quenched random site dilution. The numerical transfer matrix technique in semi
      infinite strips of finite width, together with phenomenological renormalization
      and conformal invariance, is particularly suited to putting the equilibrium
      ensemble approach to work. A method by which to extract with great precision the
      critical temperature of the model is proposed and applied. A more systematic
      finite-size scaling analysis than in previous numerical studies has been
      performed. A parallel investigation, along the lines of the two main scenarios
      currently under discussion, namely, the logarithmic corrections scenario (with
      critical exponents fixed in the Ising universality class) versus the weak
      universality scenario (critical exponents varying with the degree of disorder),
      is carried out. In interpreting our data, maximum care is constantly taken to be
      open to both possibilities. A critical discussion shows that an unambiguous
      discrimination between the two scenarios is still not possible on the basis of
      the available finite-size data.

PMID- 11970218
TI  - Dynamical universality classes of vapor deposition models with evaporation.
AB  - Growth models for vapor depositions in which evaporation and deposition can
      occur, both at a randomly chosen column and at its nearest neighbor columns
      (NNCs), are studied by Monte Carlo simulations. The growth processes in these
      models are determined by comparing local chemical potentials of the chosen column
      and its NNCs to the chemical potential of vapor. The universality classes and the
      characteristics of the models are studied by the scaling ansatz of kinetic
      roughening and by measurements of tilt-dependent currents and height step widths.
      Through measurements of the ratio of number of growth processes at NNCs to those
      at the chosen column, the key processes which are relevant to the determination
      of the universality class are also studied.

PMID- 11970219
TI  - Critical behavior of roughening transitions in parity-conserving growth
      processes.
AB  - We investigate a class of parity-conserving solid-on-solid models that describes
      the growth of an interface by the deposition and evaporation of dimers. As a key
      feature of the models, evaporation of dimers takes place only at the edges of
      terraces, leading to a roughening transition between a smooth and a rough phase.
      We consider several variants of growth models in order to identify universal and
      nonuniversal properties. Moreover, a parity-conserving polynuclear growth model
      is proposed. All variants display the same type of universal critical behavior at
      the roughening transition. Because of parity conservation, the critical behavior
      at the first few layers can be explained in terms of unidirectionally coupled
      branching annihilating random walks with an even number of offspring.

PMID- 11970220
TI  - Magnetic critical behavior of two-dimensional random-bond Potts ferromagnets in
      confined geometries.
AB  - We present a numerical study of two-dimensional random-bond Potts ferromagnets.
      The model is studied both below and above the critical value Qc=4, which
      discriminates between second- and first-order transitions in the pure system. Two
      geometries are considered, namely cylinders and square-shaped systems, and the
      critical behavior is investigated through conformal invariance techniques that
      were recently shown to be valid, even in the randomness-induced second-order
      phase transition regime Q>4. In the cylinder geometry, connectivity transfer
      matrix calculations provide a simple test to find the range of disorder
      amplitudes that is characteristic of the disordered fixed point. The scaling
      dimensions then follow from the exponential decay of correlations along the
      strip. Monte Carlo simulations of spin systems on the other hand are generally
      performed on systems of rectangular shape on the square lattice, but the data are
      then perturbed by strong surface effects. The conformal mapping of a semi
      infinite system inside a square enables us to take into account boundary effects
      explicitly and leads to an accurate determination of the scaling dimensions. The
      techniques are applied to different values of Q in the range 3-64.

PMID- 11970221
TI  - Chaotic dynamics in classical s-wave helium.
AB  - Classical dynamics of s-wave helium in the case of E<0 is investigated by the
      geometric method. The ambiguousness of the orbits after two-electron critical
      collision (TECC) is eliminated by confining the motion to the fundamental domain
      defined by r1>r2. Scattering orbits are classified into undelayed and delayed
      (resonant) according to whether they can avoid the recurrence of reaction. A
      global Smale horseshoe on the surface of section is constructed for the case of
      Z=2 which implies that the bounded motion is purely chaotic and explains the
      onset of the chaotic (resonant) scattering when the incident energy is below a
      threshold. Immediately below the threshold, the probability of resonant
      scattering increases linearly with the energy difference. Moreover, we found that
      the permitted code sequences for the scattering orbits at a given incident energy
      are determined by the principal TECC orbit. Compared with the e-Ze- collinear
      helium, the s-wave helium is less chaotic and exhibits a more intricate threshold
      behavior.

PMID- 11970222
TI  - Uncertain destination dynamics.
AB  - Certain dynamical systems exhibit a sensitivity to initial conditions in which
      the asymptotic state is selected from an infinite number of possible states. The
      phase space of such systems is foliated with "attractors," each of which is
      associated with a particular set of initial conditions. The associated uncertain
      destination dynamics can be analyzed by an appropriate reduction of the full
      system to a subsystem that explicitly yields the dynamics.

PMID- 11970223
TI  - Dynamical localization of ultracold sodium atoms.
AB  - We report a study of atomic motion in time-dependent optical potentials. We
      measure momentum transfer in parameter regimes for which the classical dynamics
      are chaotic, and observe the quantum suppression of chaos by dynamical
      localization. The high degree of control over the experimental parameters enables
      detailed comparisons with theoretical predictions, and opens new avenues for
      investigating quantum chaos.

PMID- 11970224
TI  - Chaos and reconnection in relativistic cyclotron motion in an elliptically
      polarized electric field.
AB  - A theoretical study of the relativistic cyclotron motion occurring in a uniform
      magnetic field and an oscillating electric field of arbitrary polarization is
      performed, which aims at determining the effect of the ellipticity and the
      strength of the electric field upon the integrability or nonintegrability of the
      system. Unless a circularly polarized electric field is used, the cyclotron
      system is nonintegrable and displays stochastic behavior in the region where
      resonance islands overlap. It is found, however, that the stochastic layers
      become increasingly thin as the polarization angle is moved closer toward pi/2
      (circular polarization). If the polarization angle is held fixed and the electric
      field amplitude is increased, the Kolmogorov-Arnold-Moser curves separating the
      resonance islands experience a reconnection process through which the islands are
      topologically rearranged. When the rearrangement is accomplished, the phase space
      is occupied mostly by regular trajectories.

PMID- 11970225
TI  - Boundedness of dynamical systems and chaos synchronization.
AB  - Chaos synchronization in bounded dynamical systems is studied. We use boundedness
      of trajectories within the nonreplica approach to chaos synchronization and the
      Routh-Hurwitz criterion to propose a simple method to make negative conditional
      Lyapunov exponents. The method is tested on the classical Lorenz model.

PMID- 11970226
TI  - Bifurcation to worms in electroconvection.
AB  - The primary bifurcation to electroconvection of the liquid crystal 4-ethyl-2
      fluoro-4'-[2-(trans-4-pentylcyclohexyl)ethyl]-biphenyl (I52) with planar
      alignment leads to localized structures of convection rolls known as "worms" when
      the conductivity of the fluid is relatively small. Worms coexist with the
      conduction state. They have a unique small width in the direction perpendicular
      to the director and a varying, usually much greater, length parallel to the
      director. Previous experiments had not determined whether the bifurcation to
      worms is supercritical or subcritical. We estimated the voltage V(c)
      corresponding to the stability limit of the conduction state by measuring the
      mean-square amplitude of the thermally induced fluctuations below onset and
      extrapolating to V(c). We found that worms appear already well below V(c). Thus
      the bifurcation is subcritical. Measurements of the lifetime of the conduction
      state below V(c) gave information about the voltage V(s) corresponding to the
      saddle node below which no worms form. We measured V(c) and
      epsilon(s)=V(s)2/V(c)2-1 as a function of the conductance sigma for a cell of
      thickness 24 microm and found for our sample that epsilon(s) approaches zero from
      negative values near sigma approximately 1.2 x 10(-8) Omega(-1) m(-1) as sigma
      increases. For larger sigma we found the bifurcation to be supercritical. We have
      been unable to determine so far whether the experimentally observed transition
      with decreasing sigma from a supercritical to a subcritical bifurcation occurs
      via a tricritical bifurcation, or whether the worm saddle node is disconnected
      from the primary supercritical bifurcation line as suggested by theory.

PMID- 11970227
TI  - Homoclinic crossing in open systems: chaos in periodically perturbed monopole
      plus quadrupolelike potentials.
AB  - The Melnikov method is applied to periodically perturbed open systems modeled by
      an inverse-square-law attraction center plus a quadrupolelike term. A
      compactification approach that regularizes periodic orbits at infinity is
      introduced. The (modified) Smale-Birkhoff homoclinic theorem is used to study
      transversal homoclinic intersections. A larger class of open systems with
      degenerated (nonhyperbolic) unstable periodic orbits after regularization is also
      briefly considered.

PMID- 11970228
TI  - Amplification of weak signals and stochastic resonance via on-off intermittency
      with symmetry breaking.
AB  - Nonlinear dynamical systems possessing reflection symmetry have an invariant
      subspace in the phase space. The dynamics within the invariant subspace can be
      random or chaotic. As a system parameter changes, the motion transverse to the
      invariant subspace can lose stability, leading to on-off intermittency. Under
      certain conditions, the bursting behavior is symmetry breaking. We demonstrate
      the possibility of observing multiplicative noise(chaos)-induced amplification of
      weak signal and stochastic resonance via on-off intermittency with symmetry
      breaking in a general class of symmetrical systems. Differences of this mechanism
      of stochastic resonance to that in noisy bistable or threshold systems are
      discussed.

PMID- 11970229
TI  - Spectrum of stochastic evolution operators: local matrix representation approach.
AB  - A matrix representation of the evolution operator associated with a nonlinear
      stochastic flow with additive noise is used to compute its spectrum. In the weak
      noise limit a perturbative expansion for the spectrum is formulated in terms of
      local matrix representations of the evolution operator centered on classical
      periodic orbits. The evaluation of perturbative corrections is easier to
      implement in this framework than in the standard Feynman diagram perturbation
      theory. The results are perturbative corrections to a stochastic analog of the
      Gutzwiller semiclassical spectral determinant computed to several orders beyond
      what has so far been attainable in stochastic and quantum-mechanical
      applications.

PMID- 11970230
TI  - Anderson localization in a string of microwave cavities.
AB  - The field distributions and eigenfrequencies of a microwave resonator which is
      composed of 20 identical cells have been measured. With external screws the
      periodicity of the cavity can be perturbed arbitrarily. If the perturbation is
      increased a transition from extended to localized field distributions is
      observed. For very large perturbations the field distributions show signatures of
      Anderson localization, while for smaller perturbations the field distribution is
      extended or weakly localized. The localization length of a strongly localized
      field distribution can be varied by adjusting the penetration depth of the
      screws. Shifts in the frequency spectrum of the resonator provide further
      evidence for Anderson localization.

PMID- 11970231
TI  - Ergodic properties of a generic nonintegrable quantum many-body system in the
      thermodynamic limit.
AB  - We study a generic but simple nonintegrable quantum many-body system of locally
      interacting particles, namely, a kicked-parameter (t,V) model of spinless
      fermions on a one-dimensional lattice (equivalent to a kicked Heisenberg XX-Z
      chain of 1/2 spins). The statistical properties of the dynamics (quantum
      ergodicity and quantum mixing) and the nature of quantum transport in the
      thermodynamic limit are considered as the kick parameters (which control the
      degree of nonintegrability) are varied. We find and demonstrate ballistic
      transport and nonergodic, nonmixing dynamics (implying infinite conductivity at
      all temperatures) in the integrable regime of zero or very small kick parameters,
      and more generally and importantly, also in the nonintegrable regime of
      intermediate values of kicked parameters, whereas only for sufficiently large
      kick parameters do we recover quantum ergodicity and mixing implying normal
      (diffusive) transport. We propose an order parameter (charge stiffness D) which
      controls the phase transition from nonmixing and nonergodic dynamics (ordered
      phase, D>0) to mixing and ergodic dynamics (disordered phase, D=0) in the
      thermodynamic limit. Furthermore, we find exponential decay of time correlation
      functions in the regime of mixing dynamics. The results are obtained consistently
      within three different numerical and analytical approaches: (i) time evolution of
      a finite system and direct computation of time correlation functions, (ii) full
      diagonalization of finite systems and statistical analysis of stationary data,
      and (iii) algebraic construction of quantum invariants of motion of an infinite
      system, in particular the time-averaged observables.

PMID- 11970232
TI  - Universality in quantum parametric correlations.
AB  - We investigate the universality of correlation functions of chaotic and
      disordered quantum systems as an external parameter is varied. A general scaling
      procedure is introduced which makes the theory invariant under
      reparametrizations. Under certain general conditions we show that this procedure
      is unique. The approach is illustrated with the particular case of the
      distribution of eigenvalue curvatures. We also derive a semiclassical formula for
      the nonuniversal scaling factor, and give an explicit expression valid for
      arbitrary deformations of a billiard system.

PMID- 11970233
TI  - Symbolic dynamics analysis of nonstationary data from a model of a magnetic
      system with solitons.
AB  - The probability distribution of a complexity measure is used to characterize
      chaotic states: an estimator of the algorithmic complexity of a time series of
      symbolic words is calculated within a fixed length time window, which sweeps
      through the time series analyzed. The words are derived through a symbolic
      dynamics scheme applied in an m-dimensional delay coordinate space. Time
      intervals instead of the variables of the system are used. The chaotic states of
      a model of a magnetic domain wall are characterized better by the methods
      presented than with the use of fractal dimensions and new intermittent states of
      the system were easily identified. Using an artificial nonstationary signal
      composed of different chaotic states of the Bloch wall as a test for chaos-chaos
      intermittency we demonstrate that the method developed is suitable for the
      detection and characterization of intermittency. It is also shown that
      nonstationarity in the form of a slow monotonic drift in the control parameter
      may extend the stability range of periodic states of the spatially extended
      system studied-a trackinglike phenomenon.

PMID- 11970234
TI  - Semiclassical treatment of diffraction in billiard systems with a flux line.
AB  - In billiard systems with a flux line, semiclassical approximations for the
      density of states contain contributions from periodic orbits as well as from
      diffractive orbits that are scattered on the flux line. We derive a semiclassical
      approximation for diffractive orbits that are scattered once on a flux line. This
      approximation is uniformly valid for all scattering angles. The diffractive
      contributions are necessary in order that semiclassical approximations are
      continuous if the position of the flux line is changed.

PMID- 11970235
TI  - Classical diffusion and quantum level velocities: systematic deviations from
      random matrix theory.
AB  - We study the response of the quasienergy levels in the context of quantized
      chaotic systems through the level velocity variance and relate them to classical
      diffusion coefficients using detailed semiclassical analysis. The systematic
      deviations from random matrix theory, assuming independence of eigenvectors from
      eigenvalues, are shown to be connected to classical higher-order time
      correlations of the chaotic system. We study the standard map as a specific
      example, and thus the well-known oscillatory behavior of the diffusion
      coefficient with respect to the parameter is reflected exactly in the
      oscillations of the variance of the level velocities. We study the case of mixed
      phase-space dynamics as well and note a transition in the scaling properties of
      the variance that occurs along with the classical transition to chaos.

PMID- 11970236
TI  - Coupled map car-following model and its delayed-feedback control.
AB  - This paper proposes a coupled map car-following traffic model, which describes a
      dynamical behavior of a group of road vehicles running in a single lane without
      overtaking. This model consists of a lead vehicle and following vehicles, which
      have a piecewise linear optimal velocity function. When the lead-vehicle speed is
      varied, we can observe a traffic jam in the group of the vehicles. We derive a
      condition under which the traffic jam never occurs in our model. Furthermore, in
      order to suppress the traffic jam, for each vehicle we use a dynamic version of
      decentralized delayed-feedback control proposed in [Konishi, Hirai, and Kokame,
      Phys. Rev. E 58, 3055 (1998)], and provide a systematic procedure for designing
      the controller.

PMID- 11970237
TI  - Phase space reconstruction using input-output time series data.
AB  - In this paper we suggest that an extension of a procedure recently proposed by
      Wayland et al. [Phys. Rev. Lett. 70, 580 (1993)] for recognizing determinism in
      an autonomous time series can also be used as a diagnostic for determining an
      appropriate embedding dimension for driven ("input-output") systems. We compare
      the results of this extension to the results produced by the extensions to the
      method of false nearest neighbors put forward by Rhodes and Morari [Proceedings
      of the American Control Conference, Seattle, edited by The American Automatic
      Control Council (IEEE, Piscataway, 1995)] and the method of averaged false
      nearest neighbors by Cao et al. [Int. J. Bifurcation Chaos 8, 1491 (1998)].

PMID- 11970239
TI  - Nonhyperbolic behavior in the thermostated Lorentz gas.
AB  - We show that nonhyperbolic behavior in the length-2 periodic orbits of the
      thermostated random Lorentz gas occurs only at field strengths greater than
      unity. For the thermostatted periodic Lorentz gas the range of fields is reduced
      further due to pruning. Stability analysis shows that there are three classes of
      period-2 orbits: elliptic orbits and two different hyperbolic orbits. Within the
      nonergodic elliptic region, trajectories manifest complex behavior that resembles
      that of perturbed resonant tori in Hamiltonian systems. We present a detailed
      dynamical study of the nonhyperbolic region.

PMID- 11970238
TI  - Synchronization and resonance in a driven system of coupled oscillators.
AB  - We study the noise effects in a driven system of globally coupled oscillators,
      with particular attention to the interplay between driving and noise. The self
      consistency equation for the order parameter, which measures the collective
      synchronization of the system, is derived; it is found that the total order
      parameter decreases monotonically with noise, indicating overall suppression of
      synchronization. Still, for large coupling strengths, there exists an optimal
      noise level at which the periodic (ac) component of the order parameter reaches
      its maximum. The response of the phase velocity is also examined and found to
      display resonance behavior.

PMID- 11970240
TI  - Filling transition for a wedge.
AB  - We study the formation and the shape of a liquid meniscus in a wedge with opening
      angle 2phi which is exposed to a vapor phase. By applying a suitable effective
      interface model, at liquid-vapor coexistence and at a temperature Tphi we find a
      filling transition at which the height of the meniscus becomes macroscopically
      large while the planar walls of the wedge far away from its center remain nonwet
      up to the wetting transition occurring at Tw>Tphi. Depending on the fluid and the
      substrate potential the filling transition can be either continuous or
      discontinuous. In the latter case it is accompanied by a prefilling line
      extending into the vapor phase of the bulk phase diagram and describing a
      transition from a small to a large, but finite, meniscus height. The filling and
      the prefilling transitions correspond to nonanalyticities in the surface and line
      contributions to the free energy of the fluid, respectively.

PMID- 11970241
TI  - Influence of compressibility on scaling regimes of strongly anisotropic fully
      developed turbulence.
AB  - A statistical model of strongly anisotropic fully developed turbulence of the
      weakly compressible fluid is considered by means of the field theoretic
      renormalization group. The corrections due to compressibility to the infrared
      form of the kinetic energy spectrum have been calculated in the leading order in
      the Mach number expansion. Furthermore, in this approximation the validity of the
      Kolmogorov hypothesis on the independence of the dissipation length of velocity
      correlation functions in the inertial range has been proved.

PMID- 11970242
TI  - Nonlinear viscosity and Grad's method.
AB  - The Grad ten-moment approximation (no heat flux) is analyzed for cylindrical
      symmetry in a stationary situation in which the gradients of the fluxes are
      assumed to be small. We show that if the collision term in the transport
      equation, resulting from the ten-moment approximation, is linearized in the
      fluxes, we can obtain a viscosity (etal) that depends on the gradient of the
      velocity with the correct limiting behavior for small gradients. The nonlinear
      contribution of the fluxes to the collision term are then taken into account to
      derive an expression for the viscosity (eta(nl)) as a function of the gradient of
      the velocity. A comparison between etal and eta(nl) is performed finding that the
      maximum percentage deviation between them is 0.52% when the gradient of the
      hydrodynamic velocity is positive, but when the gradient is negative the
      situation changes dramatically.

PMID- 11970243
TI  - Burnett description for plane Poiseuille flow.
AB  - Two recent works have shown that at small Knudsen number (K) the pressure and
      temperature profiles in plane Poiseuille flow exhibit a different qualitative
      behavior from the profiles obtained by the Navier-Stokes equations. Tij and
      Santos [J. Stat. Phys. 76, 1399 (1994)] used the Bhatnagar-Gross-Kook model to
      show that the temperature profile is bimodal and the pressure profile is
      nonconstant. Malek-Mansour, Baras, and Garcia [Physica A 240, 255 (1997)]
      qualitatively confirmed these predictions in computer experiments using the
      direct simulation Monte Carlo method (DSMC). In this paper we compare the DSMC
      measurements of hydrodynamic variables and non-equilibrium fluxes with numerical
      solutions of the Burnett equations. Given that they are in better agreement with
      molecular-dynamics simulations [E. Salomons and M. Mareschal, Phys. Rev. Lett.
      69, 269 (1992)] of strong shock waves than Navier-Stokes [F. J. Uribe, R. M.
      Velasco, and L. S. Garcia-Colin, Phys. Rev. Lett. 81, 2044 (1998)], and that they
      are second order in Knudsen number suggests that the Burnett equations may
      provide a better description for large K. We find that for plane Poiseuille flow
      the Burnett equations do not predict the bimodal temperature profile but do
      recover many of the other anomalous features (e.g., nonconstant pressure and
      nonzero parallel heat flux).

PMID- 11970244
TI  - Frequency-dependent viscosity of xenon near the critical point.
AB  - We used a novel, overdamped oscillator aboard the Space Shuttle to measure the
      viscosity eta of xenon near its critical density rho(c) and temperature Tc. In
      microgravity, useful data were obtained within 0.1 mK of Tc, corresponding to a
      reduced temperature t=(T-Tc)/Tc=3 x 10(-7). Because they avoid the detrimental
      effects of gravity at temperatures two decades closer to T(c) than the best
      ground measurements, the data directly reveal the expected power-law behavior eta
      proportional, variant t(-nuz(eta)). Here nu is the correlation length exponent,
      and our result for the viscosity exponent is z(eta)=0.0690+/-0.0006. (All
      uncertainties are one standard uncertainty.) Our value for z(eta) depends only
      weakly on the form of the viscosity crossover function, and it agrees with the
      value 0.067+/-0.002 obtained from a recent two-loop perturbation expansion [H.
      Hao, R.A. Ferrell, and J.K. Bhattacharjee, (unpublished)]. The measurements
      spanned the frequency range 2 Hz< or = f < or =12 Hz and revealed viscoelasticity
      when t < or = 10(-5), further from Tc than predicted. The viscoelasticity's
      frequency dependence scales as Aftau, where tau is the fluctuation-decay time.
      The fitted value of the viscoelastic time-scale parameter A is 2.0+/-0.3 times
      the result of a one-loop perturbation calculation. Near Tc, the xenon's
      calculated time constant for thermal diffusion exceeded days. Nevertheless, the
      viscosity results were independent of the xenon's temperature history, indicating
      that the density was kept near rho(c) by judicious choices of the temperature
      versus time program. Deliberately bad choices led to large density
      inhomogeneities. At t>10(-5), the xenon approached equilibrium much faster than
      expected, suggesting that convection driven by microgravity and by electric
      fields slowly stirred the sample.

PMID- 11970245
TI  - Alternative optical equation for dielectric liquids.
AB  - A "statistically permanent" pair of molecules interacting by dispersion forces,
      as a unit element of a simple cubic "crystal" modeling a nonpolar liquid
      dielectric at a given thermal state, has been used to explain low and high
      pressure refractive index n measurements. It has been shown that the equation
      (epsilon-1)2epsilon+1 / 9epsilon=c(lambda)r exp r(2) / 1-T/T(l)[where epsilon
      identical withn(2), c(lambda)>or=1 close to a unity liquid constant for
      wavelength lambda, r =4pirhoalpha/3, rho is the number density, alpha is the mean
      polarizability of a free molecule, T(l) is the internal temperature = a/RV, a is
      the van der Waals constant identical with(27/64)(RT(c))(2)/p(c), and R is the
      universal gas constant] is more accurate than any already known optical equation
      of liquids. The small changes in Lorentz-Lorenz refraction L identical
      with(epsilon-1)V/(epsilon+2) according to ( partial differentialL/ partial
      differentialp)(T)<0 and ( partial differentialL/ partial differentialT)(p)>(
      partial differentialL/ partial differentialT)(V)>0 are expected and observed in
      all pressure ranges. The translational fluctuation parameter <x(-6)> of the right
      order of magnitude is obtained from n.

PMID- 11970246
TI  - Relation of shear viscosity and self-diffusion coefficient for simple liquids.
AB  - A Stokes-Einstein-type relation is derived for the potential part of the shear
      viscosity of a simple liquid by means of statistical mechanics. The product of
      the shear viscosity and the self-diffusion coefficient is shown to be expressible
      in terms of the pair correlation function and the intermolecular force as well as
      the density. The shear viscosity formula, consisting of kinetic and potential
      parts and given in terms of the self-diffusion coefficient, is tested against
      experimental data with regard to the temperature and density dependence of the
      shear viscosity. Given the self-diffusion coefficient determined by experiment or
      simulations, the viscosity formula involving the Stokes-Einstein relation
      obtained produces the shear viscosity of argon, krypton, and xenon, in good
      agreement with experiment in the case of temperatures well away from the triple
      point. However, in the neighborhood of the triple point of argon examined, a
      cutoff parameter, which is a measure of the range of density variation, is needed
      to account for the experimental data. The applicability of the Stokes-Einstein
      relation to molecular particles is assessed, and it is found to remain applicable
      in the range of density and temperature examined.

PMID- 11970247
TI  - Nonbound dislocations in hexagonal patterns: pentagon lines in surface-tension
      driven Benard convection.
AB  - We report on a novel class of defects in a hexagonal pattern which we call
      pentalines. They are built up of two nonbound dislocations and are orientated
      parallel to the roll axis of the mode free of a dislocation. A pentaline has its
      origin in a transformation of the penta-hepta defect (PHD), taking place at
      higher supercriticality. The underlying mechanism consists in a combination of
      glide and climb motion of the original dislocations bound to the PHD. We
      demonstrate that the pentalines play an important role within the transition from
      hexagonal towards square convection cells, observed in surface-tension-driven
      Benard convection.

PMID- 11970248
TI  - Relation between transport and thermodynamic properties in liquid sp-electron
      metals near freezing.
AB  - Classical statistical mechanics based on assumed pair potentials leads, for
      liquid metals, to an approximate relation between shear viscosity eta, surface
      tension sigma, and thermal velocity vT defined as (kBT/M)(1/2), with M the ionic
      mass. Theory predicts for the dimensionless grouping sigma/etav(T) evaluated at
      the melting temperature Tm a single value 15 / 16; liquid sp-electron metals
      exhibit, however, a scatter from around 0.7 to 2.3. Therefore, an alternative
      grouping sigma/etav(s), with v(s) the velocity of sound, is considered here in
      detail, first using experimental data and second using both theoretical and
      semiempirical arguments. The scatter of sigma/etav(s) at Tm is less than for the
      earlier grouping, and also insight can be gained as to various physical factors
      determining sigma/etav(s). In essence, this quantity is proportional to the
      product of two factors, both dimensionless, namely, the surface thickness L
      measured in units of the mean interionic separation, and the square root of the
      energy Mv(2)s, measured in units of the thermal energy kBTm. Theoretical
      estimates are made of both of these factors, in fair accord with the experimental
      data.

PMID- 11970249
TI  - Reciprocity and cross coupling of two-phase flow in porous media from Onsager
      theory.
AB  - The symmetry properties of the permeability matrix in the macroscopic transport
      law for two-phase immiscible flow in porous media are investigated. The porous
      medium is treated as a single, closed thermodynamic system being forced by piston
      reservoirs. This construction is used to relate the Darcy fluxes to the time
      derivatives of the piston motion, and to identify the fluxes and forces in the
      Onsager sense. When the surface-tension forces that develop on the fluid
      interface are linear in the interface displacement, Onsager's theory is directly
      applicable and the permeability matrix must be symmetric. This argument is
      extended to show that reciprocity still holds when surfactants modify interface
      properties.

PMID- 11970250
TI  - Biasymptotic formula for the turbulent energy cascade.
AB  - We present a family of differential models for the scaling exponents tau(p) which
      characterize the moments of the energy dissipation rate in turbulence. This
      scheme interpolates between the asymptotic values of the derivative tau'p of
      tau(p) versus p in the limits p-->+/-infinity and reproduces the negative-p part
      of the exponents spectrum tau(p) as well, in contrast with other recent
      conjectures. Each member of the family is defined by a sigmoidal function, the
      form of which remains open to theoretical investigations.

PMID- 11970251
TI  - Wavy film flows down an inclined plane: perturbation theory and general evolution
      equation for the film thickness.
AB  - Wavy film flow of incompressible Newtonian fluid down an inclined plane is
      considered. The question is posed as to the parametric conditions under which the
      description of evolution can be approximately reduced for all time to a single
      evolution equation for the film thickness. An unconventional perturbation
      approach yields the most general evolution equation and least restrictive
      conditions on its validity. The advantages of this equation for analytical and
      numerical studies of three-dimensional waves in inclined films are pointed out.

PMID- 11970252
TI  - Kinetic approach to the Gaussian thermostat in a dilute sheared gas in the
      thermodynamic limit.
AB  - A dilute gas of particles with short range interactions is considered in a
      shearing stationary state. A Gaussian thermostat keeps the total kinetic energy
      constant. For infinitely many particles it is shown that the thermostat becomes a
      friction force with constant friction coefficient. For finite number of particles
      N, the fluctuations around this constant are of order 1/squareroot[N], and
      distributed approximately Gaussian with deviations for large fluctuations. These
      deviations prohibit a derivation of fluctuation-dissipation relations far from
      equilibrium, based on the fluctuation theorem.

PMID- 11970253
TI  - Universal long-time properties of Lagrangian statistics in the Batchelor regime
      and their application to the passive scalar problem.
AB  - We consider the transport of dynamically passive quantities in the Batchelor
      regime of a smooth in space velocity field. For the case of arbitrary temporal
      correlations of the velocity, we formulate the statistics of relevant
      characteristics of Lagrangian motion. This allows us to generalize many results
      obtained previously for strain delta correlated in time, thus answering a
      question about the universality of these results.

PMID- 11970254
TI  - Temporal surrogates of spatial turbulent statistics: the Taylor hypothesis
      revisited.
AB  - The Taylor hypothesis, which allows surrogating spatial measurements requiring
      many experimental probes by time series from one or two probes, is examined on
      the basis of a simple analytic model of turbulent statistics. The main points are
      as follows: (i) The Taylor hypothesis introduces systematic errors in the
      evaluation of scaling exponents. (ii) When the mean wind V0 is not infinitely
      larger than the root-mean-square longitudinal turbulent fluctuations v(T), the
      effective Taylor advection velocity V(ad) should take the latter into account.
      (iii) When two or more probes are employed the application of the Taylor
      hypothesis and the optimal choice of the effective advecting wind V(ad) need
      extra care. We present practical considerations for minimizing the errors
      incurred in experiments using one or two probes. (iv) Analysis of the Taylor
      hypothesis when different probes experience different mean winds is offered.

PMID- 11970255
TI  - Structure function of passive scalars in two-dimensional turbulence.
AB  - The structure function of a scalar theta(x,t), passively advected in a two
      dimensional turbulent flow u(x,t), is discussed by means of the fractal dimension
      delta1g of the passive-scalar graph. A relation between delta1g, the scaling
      exponent zeta(theta)(1) of the scalar structure function D1(theta)r, and the
      structure function D2(r) of the underlying flow field is derived. Different from
      the three-dimensional (3D) case, the 2D structure function also depends on an
      additional parameter, characteristic of the driving of the passive scalar. In the
      enstrophy inertial subrange a mean-field approximation for the velocity structure
      function gives a scaling of the passive scalar graph with delta1g<2 for
      intermediate and large values of the Prandtl number Pr. In the energy inertial
      subrange a model for the energy spectrum and thus D2(r) gives a passive-scalar
      graph scaling with exponent delta1g=5/3. Finally, we discuss an application to
      recent observations of scalar dispersion in nonuniversal 2D flows.

PMID- 11970256
TI  - Patterns in small aspect ratio Benard-Marangoni convection.
AB  - An experimental study of pattern formation in Benard-Marangoni convection with
      small aspect ratio containers and high Prandtl number fluids is presented. The
      observed stationary patterns complete previous experimental works performed at
      different values of aspect ratio and supercriticality. Detailed experimental
      studies of the flow in some single structures are described, and spatial
      bifurcations between different stationary planforms for a fixed aspect ratio are
      shown. These experimental results agree qualitatively with linear theory analysis
      and with some previous numerical works about boundary conditions effects.

PMID- 11970257
TI  - Territory covered by N random walkers.
AB  - The problem of evaluating the number of distinct sites S(N)(t) covered up to time
      t by N random walkers is revisited. For the nontrivial time regime and for N>>1
      we show how to get the asymptotic behavior of S(N)(t) and we calculate the main
      and first two corrective terms. The mth corrective term decays mildly as 1/ln(m)
      N. For d-dimensional (d=1,2,3) simple cubic lattices, the main term is the volume
      of the hypersphere of radius [(ln N(2))2Dt/d](1/2), D being the diffusion
      constant, and the corrective terms account for the roughening of the surface of
      the set of visited sites.

PMID- 11970258
TI  - Spatial stochastic resonance in one-dimensional Ising systems.
AB  - The one-dimensional Ising model is analytically studied in a spatially periodic
      and oscillatory external magnetic field using the transfer-matrix method. For low
      enough magnetic field intensities the correlation between the external magnetic
      field and the response in magnetization presents a maximum for a given
      temperature. The phenomenon can be interpreted as a resonance phenomenon induced
      by the stochastic heat bath. This "spatial stochastic resonance" is realized in
      the equilibrium state and not as a dynamical response to the external time
      periodic driving.

PMID- 11970259
TI  - Observability of stochastic resonance in neutron scattering.
AB  - The observability of the stochastic resonance phenomenon in a neutron scattering
      experiment is investigated, considering that the scatterer can hop between two
      sites. Under stochastic resonance conditions scattered intensity is transferred
      from the quasielastic region to two inelastic peaks. The magnitude of the signal
      to-noise ratio is shown to be similar to that arising in the corresponding power
      spectrum. Effects of potential asymmetry are discussed in detail. Asymmetry leads
      to a reduction of the signal-to-noise ratio by a factor of 1-xi(2), where xi is
      an asymmetry parameter which is zero for symmetric problems and equal to unity in
      a completely asymmetric case.

PMID- 11970260
TI  - Flow-distributed oscillations: stationary chemical waves in a reacting flow.
AB  - A recent prediction of stationary waves in open, reacting flows is experimentally
      verified. We show that stationary waves are generated by a mechanism whereby the
      flow carries a time-oscillating subelement, behaving like a batch reactor,
      through space while a fixed boundary condition at the inflow locks the phase of
      the oscillation. This mechanism can generate stationary patterns when all
      diffusion coefficients are equal. The experimental system is the ferroin
      catalyzed Belousov-Zhabotinsky reaction in a tubular reactor, fed by the outflow
      of a continuous flow stirred tank reactor (CSTR). Parameter conditions are such
      that the concentrations are constant in the CSTR while they oscillate in the flow
      tube.

PMID- 11970261
TI  - Exact interface model for wetting in the planar Ising model.
AB  - At the wetting transition in the two-dimensional Ising model the long contour
      (interface) gets depinned from the substrate. It is found that on sufficiently
      large length scales the statistics of the long contour are described by a unique
      probability measure corresponding to a continuous "interface model" with an
      interface binding "potential" given by a Dirac delta function supported on the
      substrate. A lattice solid-on-solid model is shown to give similar results.

PMID- 11970262
TI  - Experimental investigation of universal parametric correlators using a vibrating
      plate.
AB  - The parametric variation of the eigenfrequencies of a chaotic plate is measured
      and compared to random matrix theory using recently calculated universal
      correlation functions. The sensitivity of the flexural modes of the plate to
      pressure is used to isolate this symmetry class of modes and simplify the data
      analysis. The size of the plate is used as the external parameter and the
      eigenvalues are observed to undergo one or two oscillations in the experimental
      window. The correlations of the eigenvalues are in good agreement with
      statistical measures such as the parametric number variance, the velocity
      autocorrelation, and the intralevel velocity autocorrelation derived for the
      Gaussian orthogonal ensemble of random matrix theory. Our results show that the
      theory can be also applied to wave systems other than quantum systems.

PMID- 11970263
TI  - Anisotropic nonperturbative zero modes for passively advected magnetic fields.
AB  - An analytic assessment of the role of anisotropic corrections to the isotropic
      anomalous scaling exponents is given for the d-dimensional kinematic
      magnetohydrodynamics problem in the presence of a mean magnetic field. The
      velocity advecting the magnetic field changes very rapidly in time and scales
      with a positive exponent xi. Inertial-range anisotropic contributions to the
      scaling exponents, zeta(j), of second-order magnetic correlations are associated
      with zero modes and have been calculated nonperturbatively. For d=3, the limit xi
      ->0 yields zeta(j)=j-2+xi(2j(3)+j(2)-5j-4)/[2(4j(2)-1)], where j (j>or=2) is the
      order in the Legendre polynomial decomposition applied to correlation functions.
      Conjectures on the fact that anisotropic components cannot change the isotropic
      threshold to the dynamo effect are also made.

PMID- 11970264
TI  - Dynamical evolution of sand ripples under water.
AB  - We have performed an experimental study on the evolution of sand ripples formed
      under the action of an oscillatory flow. An annular sand-water cell was used in
      order to investigate a wide range of parameters. The sand ripples follow an
      irreversible condensation mechanism from small to large wavelength until a final
      state is reached. The wavelength and the shape of these stable sand patterns are
      mainly governed by the fluid displacement and the static angle of the granular
      media. A strong hysteresis affects the evolution of steep ripples. When the
      acceleration of the sand bed reaches a critical value, the final pattern is
      modified by the superficial fluidization of the sand layer.

PMID- 11970265
TI  - Taylor dispersion and molecular displacements in Poiseuille flow.
AB  - We have used pulsed gradient spin echo (PGSE) NMR to measure longitudinal
      displacements of octane molecules undergoing Poiseuille flow in a 150 microm
      diameter pipe, accessing time scales which approach the Taylor dispersion limit.
      We monitor the change in displacement distribution which occurs as molecules
      undergoing Brownian motion sample an increasing proportion of the ensemble of
      streamlines, observing the effects of wall collisions and the gradual transition
      of the propagator from Poiseuille to Taylor-Aris behavior. The further use of a
      double PGSE sequence allows the direct measurement of the stochastic part of the
      motion alone.

PMID- 11970266
TI  - Multistable alignment in free suspended nematic liquid crystal films.
AB  - Two different types of orientation were observed in free suspended nematic liquid
      crystal films. The alignment was either homeotropic or planar, depending on the
      time during which the film was cooling from the isotropic state to the liquid
      crystal one. It was shown that nucleation of defects makes planar orientation
      preferable.

PMID- 11970267
TI  - Possibility of rarefaction shock wave under short pulse laser ablation of solids.
AB  - Attention is drawn to a phenomenon that may give a radically different
      explanation for the recent observations of the system of dark rings above a solid
      surface vaporized by a short laser pulse. If a substance is heated to near
      critical temperature, the existence of the compression shock wave becomes
      impossible, whereas the rarefaction wave takes a form of shock. The rarefaction
      shock can be considered as an interface in the expanding near-critical substance
      to form Newton rings in time-resolved optical microscopy experiments. The
      qualitative picture of the laser-ablated material expansion in vacuum with the
      generation of the rarefaction shock is discussed.

PMID- 11970268
TI  - Long-range density fluctuations in a symmetric diblock copolymer.
AB  - We present an experimental piece of evidence of the excess small-angle-scattering
      in a nearly symmetric diblock copolymer. This phenomenon is observed only in the
      two-phase coexistence region of the ordered and disordered phases near the order
      disorder transition temperature, using the ultra-small-angle x-ray scattering
      method. This excess scattering is found to be caused by the difference of the
      density between the ordered and disordered phases in the coexistence region.

PMID- 11970269
TI  - Formation of a conducting channel in air by self-guided femtosecond laser pulses.
AB  - We report a drastic reduction of air resistivity following the passage of a self
      guided femtosecond pulse from a Ti:sapphire laser system at 800 nm with energies
      per pulse between 1 and 14 mJ and a pulse duration of 120 fs. Connected plasma
      filaments with a length that can exceed 150 cm are created by these pulses. The
      presence of a conducting plasma channel results from multiphoton ionization of
      air molecules in the filament core.

PMID- 11970270
TI  - Instabilities of cavity solitons in optical parametric oscillators.
AB  - Using an example of cavity solitons in optical parametric oscillators it is
      demonstrated that Hopf instability of these dissipative structures can be
      directly associated with internal modes of their conservative counterparts. The
      latter ones are free propagating quadratic solitons in this case. Linear
      stability analysis and numerical simulation also reveal multistability and
      complex instability induced spatiotemporal dynamics of single and multihump
      cavity solitons.

PMID- 11970271
TI  - Dynamics of chevron structure formation. II. Permeation-dominated phenomena.
AB  - This paper continues a study of the dynamics of chevron formation in smectic-A
      liquid crystals in samples with boundary conditions apparently favoring the
      bookshelf structure, with uniform layers perpendicular to the sample cell plane.
      The chevron structure that arises when the sample is cooled results from the
      mismatch between preferred bulk and surface layer thicknesses. In a previous
      paper we considered relaxation driven by the strong coupling between layer
      deformation and fluid flow. In this paper we discuss the alternative scenario in
      which boundary conditions suppress this coupling. Layer deformation now occurs by
      layer relaxation in the absence of fluid flow. This process is extremely slow and
      is governed by the nonlinear Fisher-Kolmogorov equation. Chevrons do form under
      some circumstances, but the process is irregular, and quasimetastable jagged
      multi-edged multi-tip-like structures can occur on intermediate time scales for
      suitable layer strains. In the absence of surface layer pinning, layer slippage
      occurs at the surfaces. We also examine the possibility that deformation may
      occur through a wave of invasion destroying the bookshelf region.

PMID- 11970272
TI  - Interaction of spherical particles dispersed in a liquid crystal above the
      nematic-isotropic phase transition.
AB  - The effective interaction of micron-size particles immersed in a nematic liquid
      crystal at temperatures above the nematic-isotropic phase transition is examined.
      Using the Landau-de Gennes theory we describe the surface-induced ordering of the
      liquid crystal. Modeling a spherical particle by a sequence of conical surfaces
      enables us to draw an analogy with the partial ordering in a thin nematic film
      and to obtain an analytical expression for the two-particle interaction. Special
      attention is paid to the dependence of the effective interaction on temperature
      and on the interfacial coupling parameters, which are chosen in agreement with
      recent experiments. We show that the interaction as a function of the
      interparticle distance exhibits a potential barrier of the order of kT. The
      height of the barrier decreases exponentially with increasing temperature while
      it grows linearly with the interfacial coupling parameters.

PMID- 11970273
TI  - NMR spectra from Monte Carlo simulations of polymer dispersed liquid crystals.
AB  - We present the calculation of NMR line shapes, including dynamical effects, of
      polymer dispersed liquid crystals starting from the Monte Carlo configurations
      simulated for a lattice spin model. We consider droplets with radial, bipolar,
      and random boundary conditions and examine to what extent their predicted
      deuterium NMR spectra differ in the presence of molecular motion.

PMID- 11970274
TI  - Mesoscopic model for the viscosities of nematic liquid crystals.
AB  - Based on the definition of the mesoscopic concept by Blenk et al. [Physica A 174,
      119 (1991); J. Noneq. Therm. 16, 67 (1991); Mol. Cryst. Liq. Cryst. 204, 133
      (1991)] an approach to calculate the Leslie viscosity coefficients for nematic
      liquid crystals is presented. The approach rests upon the mesoscopic stress
      tensor, whose structure is assumed similar to the macroscopic Leslie viscous
      stress. The proposed form is also the main dissipation part of the mesoscopic
      Navier-Stokes equation. On the basis of the correspondence between microscopic
      and mesoscopic scales a mean-field mesoscopic potential is introduced. It allows
      us to obtain the stress tensor angular velocity of the free rotating molecules
      with the help of the orientational Fokker-Planck equation. The macroscopic stress
      tensor is calculated as an average of the mesoscopic counterpart. Appropriate
      relations among mesoscopic viscosities have been found. The mesoscopic analysis
      results are shown to be consistent with the diffusional model of Kuzuu-Doi and
      Osipov-Terentjev with the exception of the shear viscosity alpha(4). In the
      nematic phase alpha(4) is shown to have two contributions: isotropic and nematic.
      There exists an indication that the influence of the isotropic part is dominant
      over the nematic part. The so-called microscopic stress tensor used in the
      microscopic theories is shown to be the mean-field potential-dependent
      representation of the mesoscopic stress tensor. In the limiting case of total
      alignment the Leslie coefficients are estimated for the diffusional and
      mesoscopic models. They are compared to the results of the affine transformation
      model of the perfectly ordered systems. This comparison shows disagreement
      concerning the rotational viscosity, whereas the coefficients characteristic for
      the symmetric part of the viscous stress tensor remain the same. The difference
      is caused by the hindered diffusion in the affine model case.

PMID- 11970275
TI  - Molecular theory of HexB-SmA-isotropic transitions in ultrathin liquid crystal
      films.
AB  - A microscopic theory is developed to treat the ultrathin film of liquid crystals
      of molecules that have no cylindrical symmetry. The Hamiltonian is derived from
      the basic electrostatic interaction among electrons by considering the dipole
      dipole and dipole-quadrupole interactions between nonchiral molecules. It
      exhibits the in-plane sixfold symmetry. From a unified model with the same
      interaction constants we are able to explain simultaneously the layer-thinning
      SmA-I transition, the anomalous multiplex heat capacity, the strong singularity
      in the HexB-SmA transition, and the coexistence of different phases. The
      theoretical calculations agree quantitatively with recent experimental results
      for the free-standing 54COOBC films.

PMID- 11970276
TI  - Dynamics of water coning.
AB  - Water beneath a layer of oil in a producing reservoir may rise and form a bell
      shaped cone in the vicinity of the well. We discuss how the dynamics of cone
      formation in two dimensions depends on the gravitational contrast, the
      interfacial tension, and the flow rate of oil. For a constant flow rate below a
      critical rate Q(c), stable cones are formed. At rates above Q(c), two dynamical
      regimes are expected. These are slow initial formation and fast breakthrough to
      the well. Quasi-two-dimensional transparent porous models were used to perform
      cone formation experiments. Effective acceleration due to gravity was
      systematically varied. The experiments were simulated using a stochastic model
      based on invasion percolation in which capillary forces were explicitly taken
      into account. We find agreement between experiments and simulations, and
      consistency with the theoretical predictions.

PMID- 11970277
TI  - Growth of a single-domain smectic phase in a thin liquid-crystalline polymer
      film.
AB  - The ordering process and kinetics in thin films (200-800-nm thick) of a
      thermotropic side-chain liquid-crystalline polymer have been investigated
      vertically and laterally, respectively, by x-ray reflectivity and atomic-force
      microscopy. The original smooth and amorphous spin-coated films initially become
      corrugated upon annealing in the smectic mesophase. The roughening of the surface
      results from the formation of randomly oriented microcrystalline domains in the
      film. At the same time, however, a laterally macroscopic crystal starts to grow
      from the substrate surface in the direction of the polymer-air interface at the
      expense of these domain structures. Finally, a nicely ordered single crystal with
      parallel-ordered bilayers is formed in the film as well as at the polymer-air
      interface. This one-dimensional crystallization, actually recrystallization,
      depends strongly on the temperature due to viscosity effects. At low
      temperatures, just above the glass-transition temperature, the ordering is very
      slow, but with increasing temperature the crystal growth is faster. An Arrhenius
      type plot gives an activation energy of 122 kJ/mol, which we ascribe to the
      expected reorientations of the mesogenic groups during the recrystallization
      process.

PMID- 11970278
TI  - Statistical mechanics of charged polymers in electrolyte solutions: a lattice
      field theory approach.
AB  - The lattice field theory approach to the statistical mechanics of a classical
      Coulomb gas [R.D. Coalson and A. Duncan, J. Chem. Phys. 97, 5653 (1992)] is
      generalized to include charged polymer chains. Saddle-point analysis is done on
      the functional integral representing the partition function of the full system.
      Mean-field level analysis requires extremization of a real-valued functional
      which possesses a single minimum, thus guaranteeing a unique solution. The full
      mean-field equations for such a coupled system are derived, as well as the
      leading (one-loop) fluctuation corrections. Two different numerical real-space
      lattice procedures are developed to implement the generalized theory; these are
      applied to the problem of a charged polymer confined to a spherical cavity in an
      electrolyte solution. The results provide insight into the physics of confined
      polyelectrolytes.

PMID- 11970280
TI  - Elongation of confined ferrofluid droplets under applied fields.
AB  - Ferrofluids are strongly paramagnetic liquids. We study the behavior of
      ferrofluid droplets confined between two parallel plates with a weak applied
      field parallel to the plates. The droplets elongate under the applied field to
      reduce their demagnetizing energy and reach an equilibrium shape where the
      magnetic forces balance against the surface tension. This elongation varies
      logarithmically with aspect ratio of droplet thickness to its original radius, in
      contrast to the behavior of unconfined droplets. Experimental studies of a
      ferrofluid-water-surfactant emulsion confirm this prediction.

PMID- 11970279
TI  - Metastable versus unstable transients at the onset of a shear-induced phase
      transition.
AB  - We measure the transient stress response at the onset of shear of a wormlike
      micelles solution which shows an inhomogenous banded flow pattern above a
      characteristic rate (.)gamma(t.). Depending on the magnitude of the excess rate
      above (.)gamma(t.), we identify two distinct types of stress response that
      correspond, respectively, to the metastable and to the unstable regimes, for the
      formation of the banded flow. This feature further underlines the analogy between
      the spontaneous formation of a banded flow and a first-order phase transition.

PMID- 11970281
TI  - Orientational order in model dipolar fluids.
AB  - Fluids of hard spheres each carrying two parallel point dipoles have been
      investigated using constant-volume Monte Carlo computer simulations. The results
      show that both ferroelectric and antiferroelectric fluid phases can be stabilized
      at high density and low temperature by dipolar interactions alone, if the
      separation between the dipoles on each sphere is sufficiently large. A simple
      lattice calculation provides some insight into the balance between dipole energy
      and orientational entropy which governs the polarization state.

PMID- 11970282
TI  - Two-phase flow through porous media in the fixed-contact-line regime.
AB  - The complete set of equations controlling immiscible two-phase flow through
      porous media are derived from first principles under the sole restriction that
      contact lines between the two fluids and the grain surfaces are not allowed to
      migrate irreversibly. Because rough grain surfaces have the ability to trap
      contact lines over significant ranges of capillary-pressure variation, such laws
      are of practical interest. As distinct from previous coarse-graining work, we
      explicitly allow for the stretching of the fluid interface, which results in
      considerable nonlinearity at the macroscopic scale. The laws are obtained through
      an asymptotic analysis and have several new features compared to the standard
      laws conventionally used in two-phase flow modeling. These include the need to
      (i) distinguish between measurable fluxes and the volume-averaged flow; (ii)
      allow for flow induced by the time rate of change of the capillary pressure; and
      (iii) include quadratic-force terms in the generalized Darcy laws when
      macroscopic-pressure diffusion is slow (as defined herein).

PMID- 11970283
TI  - Thermodynamics of a nonionic sponge phase.
AB  - Different suggestions for the mechanism governing the narrow stability of the
      L(3) (sponge) phase have led to a series of debates in recent years. There have
      been several models developed to describe such a mechanism via thermodynamics. To
      date, experimental data are insufficient to test present theories. In this study,
      we revisit the sponge phase with two series of thermodynamic data performed on
      the well-characterized C(12)E(5)-n-decane-H(2)O system. These thermodynamic data
      sets stem from phase equilibrium and static light scattering experiments designed
      to link system-specific parameters such as the temperature dependence of the
      spontaneous curvature H(o) and the two bending moduli kappa and (-)kappa, which
      have only been loosely connected in earlier experiments. The use of a well
      characterized system is important in that it allows usage of molecular
      descriptors from earlier studies to reduce fit parameters. Another advantage for
      using this system is that its phase behavior is analogous to a two-component
      system which, from an experimental standpoint, is more practical to perform
      accurate measurements and, from a theoretical standpoint, more simple to model.
      In the present investigation, we use these tools to quantitatively test
      parameters obtained by different experimental techniques and assumptions
      inherited in theoretical models designed to interpret them.

PMID- 11970284
TI  - Monte Carlo simulation of submonolayer vapor-deposition polymerization.
AB  - In this paper, we propose a Monte Carlo simulation model for the initial growth
      of polymer films by considering only monomer surface diffusion in the vapor
      deposition polymerization process. In the model, monomers are deposited randomly
      on a two-dimensional square lattice with periodic boundary conditions and are
      allowed to diffuse with nearest neighbor hops. Whenever monomers meet, they stop
      diffusing and form a stable dimer. When a diffusing or deposited monomer
      encounters one of the ends of a polymer (L>1), it stops moving and attaches to
      the polymer. Attachment of monomers or other polymers is allowed only at the two
      ends of the polymer. We have shown that there are three distinct growth regimes
      for surface coverages theta<0.5: a low-coverage initiation regime (I), a chain
      propagation regime (P), and a saturation regime (S). In both regimes I and P, the
      growth is similar to the molecular beam epitaxy model. We examine in detail the
      scaling relations for the chain length distribution, which agree quite well with
      results of a rate equation. However, in regime S, our model gives very different
      kinetics. The breakdown of scaling at higher coverages is due to the fact that
      long-chain polymers have partitioned the lattice with inactive sites. This
      inhibits further polymer growth and enhances production of dimers, shifting the
      chain distribution to favor shorter polymers and driving the average molecular
      weight down. The chain configuration initially is similar to a path taken in a
      diffusion-limited self-avoiding walk. However, at high coverages, due to the
      correlation of long polymer chains, the polymer chains tend to be compact.

PMID- 11970285
TI  - Surface hydrodynamics on a freely standing layer of a polymer solution.
AB  - The dispersion relation and the power spectrum of the surface modes on a surface
      active, freely standing film of a concentrated polymer solution are studied with
      a two-component fluid model of a viscoelastic material. The diagram of bending
      modes is obtained from an asymptotic analysis of the dispersion equation when the
      bending rigidity modulus is the main elastic effect on the layer interface. The
      resulting dynamical structure factor provides the characteristic squeezing and
      undulation surface modes of the interfaces driven by thermal fluctuations or by a
      weak external perturbation. The effect of interfacial and bulk elastic properties
      on the power spectrum of the scattered light is studied. In the regime of an
      elastic solution, finite-thickness effects and bulk elastic properties of the
      layer sustain a train of elastic peaks when the wavelength of thermal
      fluctuations is comparable to the thickness of the layer. Interfacial elasticity
      properties increase the strength and shift all resonance frequency peaks
      producing a less intense quasielastic spectrum around zero frequency.

PMID- 11970286
TI  - Doppler shift anisotropy in small angle neutron scattering.
AB  - The two-dimensional patterns in our small angle neutron scattering (SANS)
      experiments from rapidly moving aerosols are anisotropic. To test the kinematic
      theory of two-body scattering that describes the anisotropy, we conducted SANS
      experiments using a constant source of D2O aerosol with droplets moving at
      approximately 440 m/s, and varied the neutron velocity from 267 to 800 m/s. The
      theoretically predicted anisotropy of the laboratory scattering intensities
      agrees well with the experimental results. Based on an analysis of the scattering
      intensity in the Guinier region, we also determined the particle velocity. The
      results are in very good agreement with independent velocity estimates based on
      supersonic flow measurements.

PMID- 11970287
TI  - Orientation of particles in an electrorheological fluid under an electric field.
AB  - The orientation of the particles in an electrorheological fluid under an electric
      field has been studied. Triglycine sulfate (TGS)-wax mixtures were applied in
      this study. Here the TGS particles are in the ferroelectric phase with
      spontaneous polarization p(s) in the <010> direction at below the Curie
      temperature T(C) and become paraelectric without a permanent electric moment at
      above T(C). By measuring x-ray-diffraction intensities of TGS/wax samples under
      an electric field at below and above T(C), respectively, it is found that the
      particles with spontaneous polarization turn their p(s) vectors to the direction
      of the external electric field in addition to forming chains or columns. However,
      the particles without permanent moment only form chains or columns, in which no
      preferred orientation of the particles can be observed. The preferred orientation
      degree is determined by comparing the diffraction intensity in these two cases.

PMID- 11970288
TI  - Transport coefficients for granular media from molecular dynamics simulations.
AB  - Under many conditions, macroscopic grains flow like a fluid; kinetic theory
      predicts continuum equations of motion for this granular fluid. In order to test
      the theory, we perform event-driven molecular simulations of a two-dimensional
      gas of inelastic hard disks, driven by contact with a heat bath. Even for strong
      dissipation, high densities, and small numbers of particles, we find that
      continuum theory describes the system well. With a bath that heats the gas
      homogeneously, strong velocity correlations produce a slightly smaller energy
      loss due to inelastic collisions than that predicted by kinetic theory. With an
      inhomogeneous heat bath, thermal or velocity gradients are induced. Determination
      of the resulting fluxes allows calculation of the thermal conductivity and shear
      viscosity, which are compared to the predictions of granular kinetic theory, and
      which can be used in continuum modeling of granular flows. The shear viscosity is
      close to the prediction of kinetic theory, while the thermal conductivity can be
      overestimated by a factor of 2; in each case, transport is lowered with
      increasing inelasticity.

PMID- 11970289
TI  - Kinetic model of phase separation in binary mixtures with hard mobile impurities.
AB  - We develop a mean-field rate-equation model for the kinetics of phase separation
      in binary mixtures with hard mobile impurities. For impurities preferentially wet
      by one of the components, the phase separation is arrested in the late stage. The
      "steady-state" domain size depends strongly on both the particle diffusion
      constant and the particle concentration. We compare theoretical results with the
      simulation data and find good qualitative agreement.

PMID- 11970290
TI  - Wetting of mesoscopic soft cylinders: structure and layering transitions.
AB  - The wetting of soft mesoscopic long-chain particles is studied. As a model
      system, a cylindrical brush with poly(vinyl)pyridine side chains on the water
      surface is characterized by isotherms and x-ray reflectivity. The forces from the
      two planar interfaces and the intra- and interparticle interactions are all of
      comparable magnitude. Two layering transitions occur, one from the monolayer to
      the double layer, the next to a homogeneous multilayer. The hard wall from which
      layering starts is the smooth polymer/air interface. Indeed, they particles in
      the top layer of both the double- and the multilayer have their cylinder axis
      parallel to the surface and are laterally compressed. In contrast, the
      polymer/water interface is diffuse due to brush swelling. Generally, the long
      chain particles adjacent to the respective interfaces do not maintain their
      circular diameters. The thickness of the monolayer can be varied by a factor 3.5,
      up to 53 A. An additional phase transition occurs within the monolayer, which is
      attributed to a change of the side chains from a flattened to a compressed state
      at constant volume. Atmoic force microscope images of the monolayer transferred
      onto a solid indicate local cylinder alignment.

PMID- 11970291
TI  - Lateral interactions of charges in thin liquid films and the Berezinskii
      Kosterlitz-Thouless transition.
AB  - At certain experimental conditions, foam films drawn from aqueous surfactant
      solutions can form highly stable Newtonian films. We show that the origin of the
      film stability can be attributed to specific patterning of surfactant molecules.
      Due to high dielectric contrast, the charges, together with their electrostatic
      images, interact as needlelike charged polymers. Below a critical thickness, such
      quasipolyelectrolytes undergo the Berezinskii-Kosterlitz-Thouless transition from
      a plasmalike state to a charge neutral one. In the latter, all the charges are
      bound into dipole pairs. Inherent only in thin films, the effect leads to the
      surfactant condensation into spots that cannot be observed on a single interface
      at the same surfactant concentration. We quantify a film resistance to rupture in
      terms of a pore line tension and show that the corresponding energy barrier
      needed for pore creation is much greater than the energy of thermal excitations.

PMID- 11970292
TI  - Tethered membranes far from equilibrium: buckling dynamics.
AB  - We study the dynamics of the classical Euler buckling of compressed solid
      membranes. We relate the membrane buckling dynamics to phase ordering phenomena.
      Membranes develop a wavelike pattern whose wavelength grows, via coarsening, as a
      power of time. We find that evolving membranes are similar to growing surfaces
      ("growing interfaces") whose transverse width grows as a power of time. The
      morphology of the evolving membranes is characterized by the presence of a
      network of growing ridges where the elastic energy is mostly localized. We used
      this fact to develop a scaling theory of the buckling dynamics that gives
      analytic estimates of the coarsening exponents. Our findings show that the
      membrane buckling dynamics is characterized by a distinct scaling behavior not
      found in other coarsening phenomena.

PMID- 11970293
TI  - Statistics of shear-induced rearrangements in a two-dimensional model foam.
AB  - Under steady shear, a foam relaxes stress through intermittent rearrangements of
      bubbles accompanied by sudden drops in the stored elastic energy. We use a simple
      model of foam that incorporates both elasticity and dissipation to study the
      statistics of bubble rearrangements in terms of energy drops, the number of
      nearest neighbor changes, and the rate of neighbor-switching (T1) events. We do
      this for a two-dimensional system as a function of system size, shear rate,
      dissipation mechanism, and gas area fraction. We find that for dry foams, there
      is a well-defined quasistatic limit at low shear rates where localized
      rearrangements occur at a constant rate per unit strain, independent of both
      system size and dissipation mechanism. These results are in good qualitative
      agreement with experiments on two-dimensional and three-dimensional foams. In
      contrast, we find for progessively wetter foams that the event size distribution
      broadens into a power law that is cut off only by system size. This is consistent
      with criticality at the melting transition.

PMID- 11970294
TI  - Phase separation of rigid-rod suspensions in shear flow.
AB  - We analyze the behavior of a suspension of rigid-rod-like particles in shear flow
      using a modified version of the Doi model, and construct diagrams for phase
      coexistence under conditions of constant imposed stress and constant imposed
      strain rate, among paranematic, flow-aligning nematic, and log-rolling nematic
      states. We calculate the effective constitutive relations that would be measured
      through the regime of phase separation into shear bands. We calculate phase
      coexistence by examining the stability of interfacial steady states and find a
      wide range of possible "phase" behaviors.

PMID- 11970295
TI  - Forces between like-charged plates in electrolyte solution: ion-solvent packing
      versus electrostatic effects.
AB  - The anisotropic hypernetted-chain approximation is solved numerically for
      mixtures of neutral hard-sphere solvent particles and divalent counterions
      between charged plates. A detailed analysis of the different components of force
      acting between the plates is given. At separations of a few solvent diameters, it
      is shown that even at relatively high surface charge and moderate solvent
      density, the ionic contribution to the force tends to be dominated by the hard
      core or packing component. If the ions and solvent particles are of equal size,
      then the net pressure between the plates can be reasonably well approximated by
      adding the pressures of pure one-component ionic and solvent systems. However, if
      the ion and solvent diameters are significantly different the pressure curve is
      more complex, and the simple superposition of the ionic and solvent pressures no
      longer works. For this case, we show that to a good approximation it is still
      possible to divide the pressure into electrostatic and hard-core components, but
      now the appropriate hard-core system must itself be a mixture of neutral hard
      spheres.

PMID- 11970296
TI  - Velocity-jump instabilities in Hele-Shaw flow of associating polymer solutions.
AB  - We study fracturelike flow instabilities that arise when water is injected into a
      Hele-Shaw cell filled with aqueous solutions of associating polymers. We explore
      various polymer architectures, molecular weights, and solution concentrations.
      Simultaneous measurements of the finger tip velocity and of the pressure at the
      injection point allow us to describe the dynamics of the finger in terms of the
      "finger mobility," which relates the velocity to the pressure gradient. The flow
      discontinuities, characterized by jumps in the finger tip velocity, which are
      observed in experiments with some of the polymer solutions, can be modeled by
      using a nonmonotonic dependence between a characteristic shear stress and the
      shear rate at the tip of the finger. A simple model, which is based on a
      viscosity function containing both a Newtonian and a non-Newtonian component, and
      which predicts nonmonotonic regions when the non-Newtonian component of the
      viscosity dominates, is shown to agree with the experimental data.

PMID- 11970297
TI  - Electrostatics of a modulated membrane with specific adsorption.
AB  - We present a simple model for the electrostatic properties of a modulated
      membrane separating two different electrolyte solutions. The model is based on an
      extension to linear Gouy-Chapman theory. Starting from a Hamiltonian which
      contains a singular part for the surface contributions, we obtain within the mean
      field approach a set of equations which allows us to study the equilibrium
      between the diffuse and singular parts of the charge carriers. It is shown that
      the interface modulation leads to a higher potential of zero charge compared to
      the flat system. The value of this effect depends on the interplay between the
      height and the characteristic length of the interface modulation and the Debye
      lengths on both sides, even if the adsorption occurs only on one side of the
      interface. In the latter case, the side where no adsorption occurs locally
      exhibits a diffuse charge distribution, which averages to zero, but which makes a
      contribution to the overall potential drop across the interface. We also
      calculate the electrostatic contribution to the elastic bending modulus of the
      membrane and show that specific adsorption of ions can destabilize the flat
      interface.

PMID- 11970298
TI  - Influence of temperature and pressure on dielectric relaxation in a supercooled
      epoxy resin.
AB  - Isothermal and isobaric dielectric measurements of a supercooled epoxy resin have
      been compared. A simple scaling relates isobaric and isothermal spectra
      corresponding to the same frequency of the main loss peak. Thus, the main and
      secondary processes retain a relative weight that is the same under isothermal
      and isobaric conditions. It is inferred that both pressure and temperature,
      equivalently, are able to take effect on the relaxation processes, without
      changing the relaxation mechanism itself. Careful analysis of the structural
      relaxation time behavior revealed that the traditional free volume equation,
      where only the macroscopic volume controls the pressure evolution of free volume,
      is not a suitable description of the data, as well as a Vogel-Fulcher (VF) type
      pressure dependent function. Based on a derivative method, a different function
      for describing the bidimensional surface tau(T,P) has been proposed, which
      accounts for the observed behavior through a nonlinear correction of the critical
      temperature T0 in the VF law. The function we propose predicts pressure
      dependencies of the glass transition temperature and fragility which are
      appealing in view of a comparison with experimental results in this and many
      other systems. Interesting hints for interpreting the phenomenological results
      can be obtained within the Adam-Gibbs theory.

PMID- 11970299
TI  - Static light scattering measurements along a critical decomposition line of a
      ternary liquid mixture.
AB  - In the present paper we publish results of static light scattering measurements
      in the ternary system N,N-dimetylformamide+n-heptane+toluene. We determined the
      critical decomposition line in a concentration range of 0 up to 25 mole-%
      toluene. In seven mixtures along this line we obtained the correlation length of
      fluctuations and the generalized osmotic susceptibility as a function of the
      temperature. We apply simple power laws to calculate the critical exponents of
      both properties. The determined exponents show a systematic growth if the
      fraction of the third component increases. This growth exceeds the values for
      critical exponents that were predicted by the critical exponent renormalization.

PMID- 11970300
TI  - Molecular weight effects on chain pull-out fracture of reinforced polymeric
      interfaces.
AB  - Using Brownian dynamics, we simulate the fracture of polymer interfaces
      reinforced by diblock connector chains. We consider the mushroom regime, where
      connector chains are grafted with low surface density, for the case of large
      pulling velocities. We find that for short chains the interface fracture
      toughness depends linearly on the degree of polymerization N of the connector
      chains, while for longer chains the dependence becomes N(3/2). Based on the
      geometry of the initial chain configuration, we propose a scaling argument that
      accounts for both short and long chain limits and the crossover between them.

PMID- 11970301
TI  - Coefficient of restitution of colliding viscoelastic spheres.
AB  - We perform a dimension analysis for colliding viscoelastic spheres to show that
      the coefficient of normal restitution epsilon depends on the impact velocity g as
      epsilon=1-gamma(1)g(1/5)+gamma(2)g(2/5)-/+..., in accordance with recent
      findings. We develop a simple theory to find explicit expressions for
      coefficients gamma(1) and gamma(2). Using these and few next expansion
      coefficients for epsilon(g) we construct a Pade approximation for this function
      which may be used for a wide range of impact velocities where the concept of the
      viscoelastic collision is valid. The obtained expression reproduces quite
      accurately the existing experimental dependence epsilon(g) for ice particles.

PMID- 11970302
TI  - Small-angle x-ray scattering study of kinetics of spinodal decomposition in N
      isopropylacrylamide gels.
AB  - We present synchrotron-based time-resolved small-angle x-ray scattering (SAXS)
      measurements of spinodal decomposition in a covalently cross-linked N
      isopropylacrylamide gel. The range of wave numbers examined is well beyond the
      position of the maximum in the structure factor S(q,t). The equilibrium structure
      factor is described by the sum of a Lorentzian and a Gaussian. Following a
      temperature jump into the two phase region, the scattered intensity increases
      with time and eventually saturates. For early times the linear Cahn-Hilliard-Cook
      (CHC) theory can be used to describe the time evolution of the scattered
      intensity. From this analysis we found that the growth rate R(q) is linearly
      dependent on q(2), in agreement with mean-field theoretical predictions. However
      the Onsager transport coefficient Lambda(q) approximately q(-4), which is
      stronger than the q dependence predicted by the mean-field theory. We found that
      the growth rate R(q)>0, even though the wave numbers q probed by SAXS are greater
      than sqrt[2]q(m) where q(m) is the position of the peak of S(q,t), also in
      agreement with the mean-field predictions for a deep quench. We have also
      examined the range of validity of the linear CHC theory, and found that its
      breakdown occurs earlier at higher wave numbers. At later times, a pinning of the
      structure was observed. The relaxation to a final, microphase-separated
      morphology is faster and occurs earlier at the highest wave numbers, which probe
      length scales comparable to the average distance between crosslinks.

PMID- 11970303
TI  - Topological and spatial aspects of the hydration of solutes of extreme solvation
      entropy.
AB  - The hydration of charged Lennard-Jones spheres by simple point charge water is
      considered. Molecular dynamics and expanded ensemble simulations were used to
      compare the hydration structures surrounding solutes with extreme solvation
      entropy. The variations in the solvation entropy were analyzed in terms of
      changes in the spatial and topological structure of the hydration shells. The
      solvation entropy was found to be maximal for solutes that can replace water
      molecules in the hydrogen-bond network. Further, using a Kirkwood-type
      factorization, the solvation entropy was expanded as a sum over the partial n
      body distribution functions. The two-body solute-water contribution to the
      solvation entropy was found to exceed the full solvation entropy for solutes with
      low charge, whereas the converse is true for the other solutes. This is
      consistent with the idea that water-water correlations are enhanced by solvation
      of, for example, noble gases, whereas they are disrupted by solvation of ions.
      Further, the orientational and radial parts of the two-body solute-water entropy
      were calculated as functions of the charge of the solute. The orientational part
      has a single maximum, whereas the radial part maintains the bimodal form of the
      full solvation entropy.

PMID- 11970304
TI  - Attractive interactions between rodlike polyelectrolytes: polarization,
      crystallization, and packing.
AB  - We study the attractive interactions between rodlike charged polymers in solution
      that appear in the presence of multivalence counterions. The counterions
      condensed to the rods exhibit both a strong transversal polarization and a
      longitudinal crystalline arrangement. At short distances between the rods, the
      fraction of condensed counterions increases, and the majority of these occupy the
      region between the rods, where they minimize their repulsive interactions by
      arranging themselves into packing structures. The attractive interaction is
      strongest for multivalent counterions. Our model takes into account the hard-core
      volume of the condensed counterions, and their angular distribution around the
      rods. The hard-core constraint strongly suppresses longitudinal charge
      fluctuations.

PMID- 11970305
TI  - Simple model for granular friction.
AB  - We propose a simple phenomenological model to describe the motion of a plate on
      granular layers pushed at a constant speed. The model contains the order
      parameter characterizing the transition from a solidlike state to a liquidlike
      state. The model reproduces the hysteresis in frictional force and the universal
      profile of the slip velocity, which are observed in experiment. Our model
      predicts that the area of hysteresis loop depends on the pushing speed.

PMID- 11970306
TI  - Phase transitions in electrorheological fluids using molecular dynamics
      simulations.
AB  - A parametric study of the properties of electrorheological fluids is conducted
      using molecular dynamics (MD) simulations. The MD model is based on the solution
      of the Langevin equation for a number of suspended particles. The equations of
      motion include inertial effects, polarization forces, Stokes' drag, short range
      repulsion, and Brownian forces. Different polarization forces are considered to
      include the effect of enhancements at short range due to multipole moments
      induced by the suspended particles and other effects. The model is used to
      investigate the structural changes induced by external electric fields and by
      shear strains imposed on the system. The response times are studied as a function
      of two characteristic parameters describing the physical status of the system
      (temperature and external electric field). Finally, the stress-strain
      characteristics are studied and the yield stress is calculated as a function of
      the external electric field. The simulated response is compared with experimental
      findings.

PMID- 11970307
TI  - Similarity of relaxation in supercooled liquids and interacting arrays of
      oscillators.
AB  - Dielectric relaxation and dynamic light scattering of small molecule glass
      forming liquids invariably show that the fractional exponent beta(alpha) of the
      Kohlrausch-Williams-Watts correlation function, exp[
      (t/tau(alpha))(beta(alpha))], used to fit the alpha-relaxation data is
      temperature dependent, increasing towards the value of unity as temperature is
      raised and the relaxation time tau decreased. Comparing different glass formers,
      another property is the existence of a correlation between the value of (1
      beta(alpha)) at the glass temperature, T(g), and the T(g)-scaled temperature
      dependence of tau(alpha). We analyze a system of interacting arrays of globally
      coupled nonlinear oscillators. Each array has its oscillators coupled among
      themselves with a coupling strength K. The coupling between arrays is
      characterized by the interarray coupling strength K'. The decay of the phase
      coherence r for each array is slowed down by the interarray coupling and its time
      dependence is well approximated at sufficiently long times by exp[
      (t/tau)(beta)]. For a fixed K', on increasing K the results exhibit a decrease of
      tau and a concomitant increase of beta, similar to the properties of dielectric
      relaxation and dynamic light scattering of glass-forming liquids on increasing
      temperature. For each K' we define K(g) to be the value of K at which tau is
      equal to an arbitrarily chosen long time. We find that beta(K(g)) is correlated
      with the K(g)-scaled K dependence of tau. The results obtained in this manner at
      various fixed values of K' reproduce the relaxation properties and temperature
      dependencies of strong, intermediate, and fragile glass-forming liquids.

PMID- 11970308
TI  - Linear viscoelasticity of an inverse ferrofluid.
AB  - A magnetorheological fluid consisting of colloidal silica spheres suspended in an
      organic ferrofluid is described. Its linear viscoelastic behavior as a function
      of frequency, magnetic field strength, and silica volume fraction was
      investigated with a specially designed magnetorheometer. The storage modulus G'
      is at least an order of magnitude larger than the loss modulus G" at all magnetic
      field strengths investigated. G' does depend only weakly on frequency, and
      linearly on volume fraction. A model is presented for the high frequency limit of
      the storage modulus G'(infinity). In the model our system is treated as a
      collection of single noninteracting chains of particles. Assuming a dipolar
      magnetic interaction, theory and experiment show reasonable agreement at high
      frequencies.

PMID- 11970309
TI  - Molecular dynamics study of replica symmetry in the vulcanization transition.
AB  - We report on computer simulations of the vulcanization transition of randomly
      crosslinked polymer melts. We focus on the order parameter between different
      realizations of the same distribution of random crosslinks, as well as the
      overlap distribution of these systems.

PMID- 11970310
TI  - A constitutive relation describing the shear-banding transition.
AB  - An additional contribution to the standard expression for the shear stress must
      be considered in order to describe shear banding. A possible extension of the
      standard constitutive relation is proposed. Its physical, purely hydrodynamic
      origin is discussed. The corresponding Navier-Stokes equation is analyzed for the
      two-plate geometry, where flow gradients are assumed to exist only in the
      direction perpendicular to the two plates. The linearized Navier-Stokes equation
      is shown to be very similar to the Cahn-Hilliard equation for spinodal
      decomposition, with a similar term that stabilizes rapid spatial variations. Only
      slowly varying flow gradients are unstable. Just as in the initial stage of
      spinodal decomposition there is a most rapidly growing wavelength in the initial
      stage of the shear-banding transition, leading to a predictable number of shear
      bands. A modified Maxwell equal area construction is derived, which dictates the
      stress and the shear rates in the bands under controlled shear conditions, and
      which shows that under controlled stress conditions no true shear bands can
      coexist. The kinetics of the shear-banding transition is studied numerically. For
      the two-plate geometry it is found that there exist multiple stationary states
      under controlled shear conditions, depending on the initial state of the flow
      profile. Shear banding occurs not only when the system is initially unstable, but
      can also be induced outside the unstable region when the amplitude of the initial
      perturbation is large enough. The shear-banding transition can thus proceed via
      "spinodal demixing" (from an unstable initial state) or via "condensation." Under
      controlled stress conditions no stationary state is found. Here, coupling with
      flow gradients extending in other directions, not perpendicular to the two
      plates, should probably be taken into account.

PMID- 11970311
TI  - Effect of added copolymer on the critical properties of polymer mixtures.
AB  - Monte Carlo simulation and finite-size analysis are used to determine the
      critical properties of a binary homopolymer blend and of a polymer blend that has
      been compatibilized with a random copolymer. Determination of nu, the critical
      exponent for the correlation length, for the mixture of two homopolymers shows
      that the binary blend exhibits properties that are consistent with Ising behavior
      (nu=0.63). Similar results for the compatibilized blend show that the added
      copolymer acts very much like an impurity; lowering the mixing transition
      temperature and increasing the value of nu to a value that is in qualitative
      agreement with Fisher renormalization (nu=0.69). These results are important as
      copolymers are often added to polymer blends to act as compatibilizers. These
      results, therefore, show that the analysis of the phase behavior of these
      mixtures must be analyzed with the understanding that its critical exponents
      differ from those of a binary polymer mixture.

PMID- 11970312
TI  - Geometrical characterization of hard-sphere systems.
AB  - By using molecular dynamics simulations on a large number of hard spheres and the
      Voronoi tessellation we characterize hard-sphere systems geometrically at any
      packing fraction eta along the different branches of the phase diagram.
      Crystallization of disordered packings occurs only for a small range of packing
      fraction. For the other packing fractions the system behaves as either a fluid
      (stable or metastable) or a glass. We have studied the evolution of the
      statistics of the Voronoi tessellation during crystallization and characterized
      the apparition of order by an order parameter (Q(6)) built from spherical
      harmonics.

PMID- 11970313
TI  - Mesostructure of polymer collapse and fractal smoothing.
AB  - We investigate the internal structure of a polymer during collapse from an
      expanded coil to a compact globule. Collapse is more probable in local regions of
      high curvature, so a smoothing of the fractal polymer structure occurs that
      proceeds systematically from the shortest to the longest length scales. A
      proposed universal scaling relationship is tested by comparison with Monte Carlo
      simulations. We speculate that the universal form applies to various fractal
      systems with local processes that promote smoothness over time. The results
      complement earlier work showing that on the macroscale polymer collapse proceeds
      by driven diffusion of the polymer ends.

PMID- 11970314
TI  - Rate coding in a chain of pulse-coupled oscillators.
AB  - The input-output relation of a chain of pulse-coupled oscillators is examined.
      The oscillators capture the essential aspect of the dynamics of pacemaker
      neurons. Inputs consist of pacemaker, and noisy trains impinging upon the first
      unit in the chain. The response of the chain is defined as the spike train
      emitted by the last unit. We observe two important phenomena in the response of
      the chain for a given input train, whether pacemaker or noisy. First, the mean
      output rate of the chain is equal to the mean input rate in the range of input
      rate in which one input pulse corresponds to one output spike without phase
      locking (1:1 alternation). Second, for the same input range, the output
      interspike intervals tend to the average of the input interpulse intervals in a
      long chain of oscillators. This behavior contrasts with the fact that the
      response of a single unit depends on both input rate and pattern. We show that
      the response of the chain is reproduced by the phase transition curve which
      represents the phase shift due to a single isolated pulse stimulus. This analysis
      reveals that the averaging of the output interspike intervals is due to the
      geometrical aspect of the phase transition curve. This geometrical aspect causes
      the dependence of the response of a single unit on input pattern.

PMID- 11970315
TI  - Noise-induced breakdown of coherent collective motion in swarms.
AB  - We consider swarms formed by populations of self-propelled particles with
      attractive long-range interactions. These swarms represent multistable dynamical
      systems and can be found either in coherent traveling states or in an incoherent
      oscillatory state where translational motion of the entire swarm is absent. Under
      increasing the noise intensity, the coherent traveling state of the swarms is
      destroyed and an abrupt transition to the oscillatory state takes place.

PMID- 11970316
TI  - Information theoretical approach to the storage capacity of neural networks with
      binary weights.
AB  - The storage capacity of the perceptron with binary weights w(i)in[0,1] is derived
      by introducing the minimum distance d between input patterns. The approach
      presented in this paper is based on some results in the information theory, and
      the obtained storage capacity 0.585 is in good agreement with the well-known
      value 0.59 by the replica method in statistical physics. A strength of the
      present information theoretical approach is that it provides an easier and more
      intuitive understanding for the storage capacity than the replica method, which
      is believed to be more reliable and informative than the Vapnik-Chervonenkis
      procedure.

PMID- 11970317
TI  - Categorization in the symmetrically dilute Hopfield network.
AB  - A symmetrically dilute Hopfield model with a Hebbian learning rule is used to
      study the effects of gradual dilution and of synaptic noise on the categorization
      ability of an attractor neural network with hierarchically correlated patterns in
      a two-level structure of ancestors and descendants. Categorization consists in
      recognizing the ancestors when the network has been trained exclusively with the
      descendants. We consider a macroscopic number of ancestors, each with a finite
      number of descendants, and take into account the stochastic noise produced by the
      former in an equilibrium study of the network, by means of replica-symmetric mean
      field theory. Phase diagrams are obtained that exhibit a categorization, a spin
      glass, and a paramagnetic phase, as well as the dependence of the order
      parameters on the relevant quantities. The de Almeida-Thouless lines that limit
      the validity of the replica-symmetric results are also obtained. It is shown that
      gradual dilution increases considerably the region where a stable categorization
      phase may be found.

PMID- 11970318
TI  - Turing patterns on a sphere.
AB  - We address the problem of pattern formation on the surface of a sphere using
      Turing equations. By considering a generic reaction-diffusion model, we
      numerically investigate the patterns formed under different conditions on the
      parameter values. Our results show that a closed surface with curvature, as a
      sphere, imposes geometrical restrictions on the shape of the pattern. This is
      important in some biological systems where curvature plays an important role in
      guiding chemical, biochemical, and embryological processes.

PMID- 11970319
TI  - Universal low-frequency vibrations of proteins from a simple interaction
      potential.
AB  - A pairwise Born potential connecting the heavy atom sites within a prescribed
      cutoff, and the equation of motion method (EOM), reproduce the existence of a
      universal singularity in the low-frequency vibrational density of states of
      typical globular proteins. This is due to quasilocalization of acoustic waves and
      an analogy with a similar feature found in glasses is stressed. We explain the
      dependence of this anomaly with the effective dimensionality of the protein. The
      EOM method allows for the study of even the largest proteins with a simple
      personal computer.

PMID- 11970320
TI  - Salt-induced liquid-liquid phase separation of protein-surfactant complexes.
AB  - We report the cloud-point curve determination of lysozyme-sodium-doderyl-sulfate
      (SDS) complexes in solution. By varying the pH, salt concentration, and relative
      ratio of lysozyme to SDS, the phenomenon of clouding and liquid-liquid phase
      separation is investigated under different solution conditions. For the
      temperature, concentration, and pH ranges used in this study, the clouding
      phenomenon appears to be controlled by the electrostatic interaction between the
      lysozyme-SDS complexes. Any change in the solution condition that leads to a
      decrease in the charge on the lysozyme-SDS complexes results in an increase in
      cloud-point temperature. A generalized Flory-Huggins theory for polydisperse
      polymers is used to describe the cloud-point curve.

PMID- 11970321
TI  - Avalanche of bifurcations and hysteresis in a model of cellular differentiation.
AB  - Cellular differentiation in a developing organism is studied via a discrete
      bistable reaction-diffusion model. A system of undifferentiated cells is allowed
      to receive an inductive signal emanating from its environment. Depending on the
      form of the nonlinear reaction kinetics, this signal can trigger a series of
      bifurcations in the system. Differentiation starts at the surface where the
      signal is received and either cells change type up to a given distance or, under
      other conditions, the differentiation process propagates throughout the whole
      domain. When the signal diminishes, hysteresis is observed.

PMID- 11970322
TI  - Modulated phases in multicomponent fluid membranes.
AB  - We investigate the behavior of flexible two-component bilayer and three-component
      monolayer membranes. The components are assumed to have different spontaneous
      curvatures, and to mutually phase separate in planar membranes. As a function of
      temperature, lateral tension and bending rigidity, a rich phase behavior is
      obtained. In particular, we find three different types of modulated phases. In
      symmetric bilayers, the excess component assembles at the boundary between
      oppositely curved domains; in sufficiently asymmetric bilayers, the excess
      component is found to preferentially assemble in a single layer, with no tendency
      for segregation to the domain boundaries. We show that the phase behavior of
      three-component monolayer strongly resembles the behavior of two-component
      bilayers. In fact, in a certain, restricted region of parameter space, the two
      models can be shown to be equivalent.

PMID- 11970323
TI  - Curvature effects on activation speed and repolarization in an ionic model of
      cardiac myocytes.
AB  - Reentry is a major mechanism underlying the initiation and perpetuation of many
      cardiac arrhythmias. Stimulated ventricular myocytes give action potential
      characterized by a fast upstroke, a long-lasting plateau, and a late
      repolarization phase. The plateau phase determines the action potential duration
      (APD) during which the system remains refractory, a property essential to the
      synchronization of the heart cycle. The APD varies much with prematurity and this
      change has been shown to be the main determinant of the dynamics in models of
      paced cells and cable, and during reentry in the one-dimensional loop. Curvature
      has also been shown to be an important factor for propagation in experimental and
      theoretical cardiac extended tissue. The objective of this paper is to combine
      both curvature and prematurity effects in a kinematical model of propagation in
      cardiac tissue. First, an approximation of the ionic model is used to obtain the
      effects of curvature and prematurity on the speed of propagation, the APD, and
      the absolute refractory period. Two versions of the ionic model are studied that
      differ in their rate of excitability recovery. The functions are used in a
      kinematical model describing the propagation of period-1 solutions around an
      annulus.

PMID- 11970324
TI  - Protein ground state candidates in a simple model: an enumeration study.
AB  - The concept of the reduced set of contact maps is introduced. Using this concept
      we find the ground state candidates for a hydrophobic-polar lattice model on a
      two-dimensional square lattice. Using these results we exactly enumerate the
      native states of all proteins for a wide range of energy parameters. In this way,
      we show that there are some sequences which have an absolute native state.
      Moreover, we study the scale dependence of the number of members of the reduced
      set, the number of ground state candidates, and the number of perfectly stable
      sequences by comparing the results for sequences with lengths of 6 up to 20.

PMID- 11970325
TI  - Mechanism of stochastic resonance enhancement in neuronal models driven by 1/f
      noise.
AB  - Noise can assist neurons in the detection of weak signals via a mechanism known
      as stochastic resonance (SR). In a previous study [Phys. Lett. A 243, 281
      (1998)], we showed that when colored noise with 1/f(beta) spectrum is added to
      the FitzHugh-Nagumo (FHN) neuronal model, the optimal noise variance for SR could
      be minimized with beta approximately 1. In this study, we investigate
      analytically how the noise color (beta) affects the SR profile in a linearized
      version of the FHN model. We demonstrate that the aforementioned effect of 1/f
      noise is related to the dynamical characteristics of the model neuron, i.e., the
      refractory period, the low-pass filtering effect of the membrane capacitance, and
      the high-pass filtering effect of the recovery variable.

PMID- 11970326
TI  - Nucleation theory for helix unfolding in peptide chains.
AB  - This work introduces a microscopic nucleation theory of helix unfolding in
      peptide chains aimed at obtaining a semiempirical estimation of the critical-size
      bubble of structural distortion which may function as the kernel for helix
      destruction. A dynamic nucleation model for helix-coil transition has been
      previously introduced as an ansatz to estimate the kinetic barrier of the helix
      unfolding event [A. Fernandez and A. Colubri, J. Math. Phys. 39, 3167 (1998)].
      However, the critical size of the helix-destruction bubble, empirically obtained
      from computer simulations of favored folding pathways, has not been hitherto
      justified or determined from first principles. This requires introducing a
      microscopic treatment of the long-time torsional dynamics to assess its bearing
      on the formation of structural-distortion bubbles which eventually trigger the
      helix-unfolding process. To reach this goal we introduce two operational tenets:
      (a) The torsional dynamics of the chain may be coarse grained according to a
      discretization of the conformational state of each unit, resolved according to
      its significant torsional isomers; (b) the semiempirical formulation accounts for
      the known dependence of the enthalpy increment due to helix unfolding on the
      change in the effective solvent-exposed surface area. The functional dependence
      on bubble size of the mean time of completion of the rate-determining step for
      helix unwinding is shown to be in agreement with previous ad hoc macroscopic
      models. However, in contrast with such treatments, we infer the existence of a
      denaturation temperature from the dynamics of critical bubble formation, rather
      than introducing it as an a priori postulate. Our determination of the critical
      temperature based on nucleation kinetics theory of critical bubble formation
      coincides with those obtained from calorimetric and spectroscopic measurements.

PMID- 11970327
TI  - Statistical mechanics of protein sequences.
AB  - A statistical mechanical treatment of biological macromolecules is presented that
      includes the sequence information as an internal coordinate. Using a path
      integral representation, the canonical partition function can be represented as a
      product of a polymer configurational path integral and a sequence walk path
      integral. In most biological instances, the sequence composition influences the
      potential energy of intersubunit interaction. Consequently, the two path
      integrals are not separable, but rather "interact" via a sequence-dependent
      configurational potential. In proteins and RNA, the sequence walk occurs in
      dimensions greater than three and, therefore, will be an ideal "polymer." The
      Markovian nature of this walk can be exploited to show that all the structural
      information is contained in the sequence. This latter effect is a result of the
      dimensionality of the sequence walk and is not necessarily a result of biological
      optimization of the system.

PMID- 11970328
TI  - Scaling behavior in crackle sound during lung inflation.
AB  - During slow inflation of lung lobes, we measure a sequence of short explosive
      transient sound waves called "crackles," each consisting of an initial spike
      followed by ringing. The crackle time series is irregular and intermittent, with
      the number of spikes of size s following a power law, n(s) proportional,
      variants(-alpha), with alpha=2.77+/-0.05. We develop a model of crackle wave
      generation and propagation in a tree structure that combines the avalanchelike
      opening of airway segments with the wave propagation of crackles in a tree
      structure. The agreement between experiments and simulations suggests that (i)
      the irregularities are a consequence of structural heterogeneity in the lung,
      (ii) the intermittent behavior is due to the avalanchelike opening, and (iii) the
      scaling is a result of successive attenuations acting on the sound spikes as they
      propagate through a cascade of bifurcations along the airway tree.

PMID- 11970329
TI  - Origin of the low-frequency modes of globular proteins.
AB  - The incoherent structure factor associated with the nonexchangeable hydrogen
      atoms of carbomonoxy myoglobin at 80 and 200 K in a solvated sample has been
      computed from molecular dynamics simulations. The evaluated mean square
      displacements are almost three times larger than the experimental ones. However,
      the low-frequency band centered at 3 meV, observed in neutron scattering
      experiments, is reproduced. Evaluation of the contribution to the spectrum from
      different protein shells and backbone and side chain atoms allows us to propose
      that the low-frequency mode around 3 meV, which is a constant feature of all
      globular proteins, is mainly due to the hydrogen atoms belonging to the inner
      shell, suggesting that this mode is intrinsic to the protein itself.

PMID- 11970330
TI  - Equilibrium and dynamical properties of semiflexible chain molecules with
      confined transverse fluctuations.
AB  - The partition function of a semiflexible chain molecule with harmonically
      confined transverse fluctuations is calculated. Equilibrium properties exhibit
      qualitative differences between the weak and the strong confinement behavior. The
      relaxation times of undulations perpendicular to the chain molecule contour are
      calculated on the basis of a Langevin equation approach. With increasing
      confinement a decrease of the relaxation times is found. As a consequence the
      mean square displacement of monomers and the dynamic structure factor are
      strongly influenced by the confinement. The comparison of the calculated mean
      square displacement with diffusing wave spectroscopy measurements of actin
      filaments exhibits good agreement.

PMID- 11970331
TI  - Dielectric dispersion of biological matter: model combining Debye-type and
      "universal" responses.
AB  - The remarkably broad dielectric dispersions exhibited by solid dielectrics are
      well-known examples of the failure of Debye's relaxation theory; such dispersions
      are much better represented by a "fractional power law" described by Jonscher [A.
      K. Jonscher, Nature 267, 673 (1977)] as the "universal dielectric response." As
      it happens, however, recent experimental advances in this field suggest that
      neither of the two approaches is general enough to cope with the dielectric
      response of biological tissues, which combines striking features from both types
      of behavior. A phenomenological function is therefore proposed, which not only
      reproduces observations on biological tissues but also includes all of Jonscher's
      "universal response," the Debye, Cole-Cole, and Davidson-Cole functions, as its
      special cases.

PMID- 11970332
TI  - Effects of nonequilibrium fluctuations on ionic transport through biomembranes.
AB  - We investigate the effects of nonequilibrium fluctuations on ionic transport
      through ion channels in membranes using the concept of localized ratchet. Due to
      the localization, the ionic population in the binding site can be enhanced or
      suppressed depending upon ionic potential and its fluctuations, affecting the
      gating kinetics of the channel. The localized dichotomic fluctuations of ionic
      potential are shown to give rise to a current reversal differing from the results
      of periodic ratchets. It is also found that strong correlations between binding
      energy and membrane potential fluctuations induce resonancelike behaviors in
      ionic current as the fluctuating rate varies.

PMID- 11970333
TI  - Statistical analysis of stochastic resonance in a simple setting.
AB  - A subthreshold signal may be detected if noise is added to the data. We study a
      simple model, consisting of a constant signal to which at uniformly spaced times
      independent and identically distributed noise variables with known distribution
      are added. A detector records the times at which the noisy signal exceeds a
      threshold. There is an optimal noise level, called stochastic resonance. We
      explore the detectability of the signal in a system with one or more detectors,
      with different thresholds. We use a statistical detectability measure, the
      asymptotic variance of the best estimator of the signal from the thresholded
      data, or equivalently, the Fisher information in the data. In particular, we
      determine optimal configurations of detectors, varying the distances between the
      thresholds and the signal, as well as the noise level. The approach generalizes
      to nonconstant signals.

PMID- 11970334
TI  - Origin of the designability of protein structures.
AB  - We examined what determines the designability of two-letter codes (H and P)
      lattice proteins from three points of view. First, whether the native structure
      is searched within all possible structures or within maximally compact
      structures. Second, whether the structure of the used lattice is bipartite or
      not. Third, the effect of the length of the chain, namely, the number of monomers
      on the chain. We found that the bipartiteness of the lattice structure is not a
      main factor that determines the designability. Our results suggest that highly
      designable structures will be found when the length of the chain is sufficiently
      long to make the hydrophobic core consisting of a large enough number of
      monomers.

PMID- 11970335
TI  - Resistivity-independent dissipation of magnetohydrodynamic waves in an
      inhomogeneous plasma.
AB  - The heating of high temperature plasmas by magnetohydrodynamic (MHD) waves is one
      of the most interesting and challenging problems of plasma physics especially
      when the energy is injected into the system at length scales much larger than the
      dissipative ones. It has been conjectured that in two-dimensional MHD systems the
      possibility exists of establishing a state in which energy is dissipated at a
      rate that is independent of the Ohmic resistivity and that the time needed to
      reach such a state is finite and independent of resistivity as well. In this
      paper we prove that this is actually possible as a result of the nonlinear
      interaction of long-wavelength, "small" amplitude perturbations with a constant,
      inhomogeneous magnetic field, at least in the relatively moderate Lundquist
      number (magnetic Reynolds) range 100< or =S< or=3200.

PMID- 11970336
TI  - Shielding and charging of dust particles in the plasma sheath.
AB  - General physical features of the ion particle distribution function in the plasma
      sheath derived theoretically and observed experimentally are used for describing
      the dust shielding and charging in the sheath. It is shown that the shielding and
      charging of dust depend strongly on the degree of anisotropy of the ion
      distribution function and on the difference in the ion temperatures parallel and
      antiparallel with respect to the ion flow. Regions of "antishielding" appear both
      along the ion flow and perpendicular to it. The potential wells can be
      responsible for the attraction of other dust particles and for the creation of
      dust aggregates. This effect is related to the change of the sign of the
      dielectric function in the range of wave vectors corresponding to the strong
      Landau damping.

PMID- 11970337
TI  - Heavy-ion-beam-induced hydrodynamic effects in solid targets.
AB  - It is expected that after the completion of a new high current injector, the
      heavy-ion synchrotron (SIS) at the Gesellschaft fur Schwerionforschung (GSI)
      Darmstadt will accelerate U(+28) ions to energies of the order of 200 MeV/u. The
      use of a powerful rf buncher will reduce the pulse length to about 50 ns, and
      employment of a multiturn injection scheme will provide 2 x 10(11) particles in
      the beam that correspond to a total energy of the order of 1 kJ. This upgrade of
      the SIS, hopefully, will be completed by the end of the year 2001. These beam
      parameters lead to a specific power deposition of the order of 1-2 TW/g in solid
      matter that will provide temperatures of about 10 eV. Such low specific power
      deposition will induce hydrodynamic effects in solid materials, and one may
      design appropriate beam-target interaction experiments that could be used to
      investigate the equation of state of matter under extreme conditions. The purpose
      of this paper is to propose suitable target designs with optimized parameters for
      the future GSI experiments with the help of one and two-dimensional hydrodynamic
      simulations. Cylindrical geometry is the natural geometry for highly focused ion
      beams, and therefore cylindrical targets are the most appropriate for this type
      of interaction experiments. The numerical simulations presented in this paper
      show that one can experimentally measure the characteristic sound speed in beam
      heated targets which is an important physical parameter. Moreover, one can study
      the propagation of ion-beam-induced shock waves in the solid materials. Different
      values for the specific power deposition, namely, 10, 25, 50, and 100 kJ/g, have
      been used. In some cases the pulse length is assumed to be 40 ns while in others
      it is considered to be 50 ns. Various materials including lead, aluminum, and
      solid neon have been used.

PMID- 11970338
TI  - Quantum kinetic theory of plasmas in strong laser fields.
AB  - A kinetic theory for quantum many-particle systems in time-dependent
      electromagnetic fields is developed based on a gauge-invariant formulation. The
      resulting kinetic equation generalizes previous results to quantum systems and
      includes many-body effects. It is, in particular, applicable to the interaction
      of strong laser fields with dense correlated plasmas.

PMID- 11970339
TI  - Plasma-wall boundary layers.
AB  - According to a well established result, boundary layers develop in plasmas near
      solid surfaces. By means of a one-dimensional two-fluid model, we analyze the
      influence of charge separation and ion viscosity upon the layer structure. This
      leads to a critical discussion of the Bohm criterion. We find that, in the
      viscous limit, quasineutrality holds even at values of the Mach number above
      unity. A nonlinear boundary value problem is defined. Asymptotic matching
      techniques are used to resolve the structures of the boundary layers.

PMID- 11970340
TI  - Packings and defects of strongly coupled two-dimensional Coulomb clusters:
      numerical simulation.
AB  - The packings and defects of the strongly coupled two-dimensional Coulomb clusters
      with particle number N from a few to a few hundred with different forms of mutual
      repulsion and central confining potentials at zero temperature are investigated
      using molecular-dynamics simulation through many annealing cycles. The circular
      symmetry of the confining potential and the interplay with the mutual repulsion
      lead to the strong competition between the outer circular shells and the inner
      triangular lattice. Generic packing behaviors, such as the concentric shells with
      the classical periodic packing sequence at small N, and the triangular
      latticelike inner core surrounded by a few outer circular shells at large N are
      observed. The effects of changing the interaction and confining potentials on the
      detailed packing sequence, the radial variation of packing density, and the
      positions of the shell-triangular core interface are investigated with a detailed
      study of the cluster structures along with the formation and distribution of
      topological defects.

PMID- 11970341
TI  - Relativistic plasma viscosity of the Burnett kind.
AB  - Hydrodynamic equations to describe relativistic and ultrarelativistic plasma
      dynamics were obtained by Dzhavakhishvili and Tsintsadze [Sov. Phys. JETP 37, 666
      (1973)] using the Chapman and Enskog scheme to solve the relativistic kinetic
      equations for the different plasma species. This approach leads to a
      representation of the particle viscosities in the Navier-Stokes form and,
      therefore, some relevant physical processes, such as the Burnett type of particle
      viscosity, cannot be properly dealt with in this scheme. In this paper we employ
      the extended Grad method to derive hydrodynamic equations which include
      ultrarelativistic viscosities of the Burnett type, i.e., viscosities that depend
      not only on derivatives of the particle macroscopic velocities but also on
      derivatives of particle heat fluxes.

PMID- 11970342
TI  - Experimental and simulated neon spectra in the 10-nm wavelength region from
      tokamak and reversed field pinch plasmas.
AB  - Experimental neon spectra (in the 10-nm region), from the tokamak Tore Supra and
      the reversed field pinch experiment RFX, have been simulated. The spectra include
      lines from three neon ionization states, namely Ne(7+), Ne(6+), and Ne(5+) ions.
      Collisional radiative models have been built for these three Ne ions, considering
      electron collisional excitation and radiative decay as populating processes of
      the excited states. These models give photon emission coefficients for the
      emitted lines at electron density and temperature values corresponding to the
      experimental situations. Impurity modelling is performed using a one-dimensional
      impurity transport code, calculating the steady-state radial distribution of the
      Ne ions. The Ne line brightnesses are evaluated in a post-process subroutine and
      simulated spectra are obtained. The parts of the spectra corresponding to a
      single ionization state do not depend on the experimental conditions and show
      good agreement with the simulated single ionization state spectra. On the other
      hand, the superposition of the three spectra depends on the experimental
      conditions, as a consequence of the fact that the ion charge distribution depends
      not only on the radial profiles of the electron density and temperature, but also
      of the impurity transport coefficients. Simulations of the Ne spectra (including
      transport) give confidence in the atomic physics calculations; moreover, they
      allow the determination of the transport coefficients in the plasma region
      emitting the considered ionization states.

PMID- 11970343
TI  - Anomalous diffusion in a running sandpile model.
AB  - To explore the character of underlying transport in a sandpile, we have followed
      the motion of tracer particles. Moments of the distribution function of the
      particle positions, </x(t)-x(0)/(n)>=D(0)t(nnu(n)), are determined as a function
      of the elapsed time. The numerical results show that the transport mechanism for
      distances less than the sandpile length is superdiffusive with an exponent nu(n)
      close to 0.75, for n<1.

PMID- 11970345
TI  - Maps for distributions and their time evolution.
AB  - Many dynamical stochastic processes occur "on top" of a deterministic process. We
      present a method which uses the trajectory of the deterministic process as basis
      functions for quasiarbitrary distributions. A map for the stochastic process can
      then be computed. This may have applications in electron storage rings or other
      devices perturbed by a small stochasticity. In this paper we will look only at
      the most elementary applications of the method.

PMID- 11970344
TI  - Analysis of Gaussian beam and Bessel beam driven laser accelerators.
AB  - This paper presents a comparison of Gaussian and Bessel beam driven laser
      accelerators. The emphasis is on the vacuum beat wave accelerator (VBWA),
      employing two laser beams of differing wavelengths to impart a net acceleration
      to particles. Generation of Bessel beams by means of circular slits, holographic
      optical elements, and axicons is outlined and the image space fields are
      determined by making use of Huygens' principle. Bessel beams-like Gaussian beams
      experience a Guoy phase shift in the vicinity of a focal region, resulting in a
      phase velocity that exceeds c, the speed of light in vacuo. In the VBWA, by
      appropriate choice of parameters, the Guoy phases of the laser beams cancel out
      and the beat wave phase velocity equals c. The particle energy gain and beam
      quality are determined by making use of an analytical model as well as
      simulations. The analytical model--including the v x B interaction--predicts that
      for equal laser powers Gaussian and Bessel beams lead to identical energy gains.
      However, three-dimensional, finite-emittance simulations, allowing for detuning,
      transverse displacements, and including all the electromagnetic field components,
      show that the energy gain of a Gaussian beam driven VBWA exceeds that of a Bessel
      beam driven VBWA by a factor of 2-3. The particle beam emerging from the
      interaction is azimuthally symmetric and collimated, with a relatively small
      angular divergence. A table summarizing the ratios of final energies,
      acceleration lengths, and gradients for a number of acceleration mechanisms is
      given.

PMID- 11970346
TI  - Linear theory of multistage forward-wave amplifiers.
AB  - A small-signal theory describing multistage gyro-traveling-wave tubes (gyro-TWTs)
      is developed. Multistage configurations of gyro-TWTs as well as conventional TWTs
      seem to be attractive because of their principal ability to operate stably with a
      high gain, since the stability can be provided by a shortening of each stage
      while the gain increases with the number of stages. Two regimes of operation, far
      from cutoff and near cutoff, are considered. In the former case, the equations
      can be reduced to those describing conventional TWTs and free electron laser
      amplifiers. Thus a part of the results obtained is also valid for these devices.
      For two-stage configurations (two waveguides separated by a drift region) the
      effect of the difference in waveguide cutoff frequencies on the gain and
      bandwidth is studied. This effect has a common nature with stagger-tuning of
      cavities, which is widely used in conventional klystrons and gyroklystrons for
      bandwidth enlargement. The trade-off in gain and bandwidth of such "stagger
      tuned," two-stage gyro-TWTs and TWTs is analyzed. Also, the theory of two-stage
      gyro-TWTs with tapered waveguides and external magnetic field is discussed.

PMID- 11970347
TI  - Relaxation oscillations of the synchrotron motion caused by narrow-band
      impedances.
AB  - Although the linearized theory of small amplitude synchrotron oscillations and
      the instability thresholds derived from it have long been understood, there is no
      satisfactory description of the large amplitude highly nonlinear synchrotron
      motion of a bunched beam. With an appropriate tuning of the RF cavity impedance,
      large amplitude, low frequency, self-sustained relaxation oscillations of this
      synchrotron motion are generated. This paper presents detailed experimental data
      on such behavior, tracking code results that reproduce the important
      characteristics, and a simple analytical model that explains the key features of
      the relaxation oscillation: growth of the instability, saturation of the
      oscillation, breakup of the bunch, and subsequent damping of the system back to
      the beginning of the next cycle of the relaxation oscillation.

PMID- 11970348
TI  - Coupled-field description of zero-average dispersion management.
AB  - Using a coupled-field formalism and a standard perturbation analysis, we analyze
      a dispersion-managed system under zero-average dispersion conditions. A nonlinear
      integral equation in the spectral domain allows the determination of the critical
      strength parameter of a two-step dispersion map. Higher-order correction terms
      confirm the difference observed in the pulse shapes in each fiber and comparisons
      with fully numerical results reveal a good agreement. The existence of an
      antisymmetric dispersion-managed soliton is also confirmed.

PMID- 11970349
TI  - Wave transport in random media: the ballistic to diffusive transition.
AB  - The character of wave transport through a strongly scattering medium, excited by
      a pulsed plane-wave source, is investigated as a function of sample thickness
      over the range from about one to 13 mean free paths. To examine the behavior
      theoretically, we perform a first-principles calculation of both the frequency
      correlation function of the transmitted field and the time-domain profile of the
      transmitted intensity. These quantities are investigated experimentally using an
      ultrasonic technique, which allows us to separate the ballistic and scattered
      components of the total transmitted field, and hence to measure the scattered
      component unambiguously in thin samples. For sample thicknesses greater than
      about four mean free paths, we find good agreement between our theory, the
      diffusion approximation, and our experimental data for both the frequency
      correlation function and the intensity time profile. In thinner samples, there
      are systematic differences between theory and experiment. To characterize the
      transition from ballistic to diffusive behavior in thin samples, we focus on the
      arrival time of the peak in the scattered component of the transmitted intensity;
      unexpectedly we find that the scattered peak arrival time exhibits an abrupt
      crossover between ballistic and diffusive behavior when the ratio of sample
      thickness to mean free path, L/l, is approximately equal to 3. Excellent
      agreement is obtained between our theory and experiment for this crossover
      behavior over the entire range of sample thicknesses investigated.

PMID- 11970350
TI  - Sound propagation in urban areas: a periodic disposition of buildings.
AB  - A numerical simulation of background noise propagation is performed for a network
      of hexagonal buildings. The obtained results suggest that the prediction of
      background noise in urban spaces is possible by means of a modified diffusion
      equation using two parameters: the diffusion coefficient that expresses the
      spreading out of noise resulting from diffuse scattering and multiple reflections
      by buildings, and an attenuation term accounting for the wall absorption,
      atmospheric attenuation, and absorption by the open top. The dependence of the
      diffusion coefficient with geometrical shapes and the diffusive nature of the
      buildings are investigated in the case of a periodic disposition of hexagonal
      buildings.

PMID- 11970351
TI  - Switching of electromagnetic waves by two-layered periodic dielectric structures.
AB  - The propagation of electromagnetic waves in two-layered periodic dielectric
      structures is investigated. The systematic dependence of the reflection
      coefficient on the parameters characterizing the structure is studied in detail.
      Using results of this exact analysis we investigate the influence of variation of
      the structure parameters on the reflection and transmission coefficients. As an
      example, we consider the changes in the structure parameters under an elastic
      stress. We show that under practically realizable conditions the reflection and
      transmission of the electromagnetic wave can be changed by as much as 80-90 % by
      creating a constant elastic stress inside the structure.

PMID- 11970352
TI  - Soliton generation in optical fibers for a dual-frequency input.
AB  - We analyze scenarios of soliton generation in an ideal fiber for an input that
      consists of either two in-phase or out-of-phase solitonlike optical pulses at
      different frequencies. In both cases the relationship between the structure of
      the emerging solitons and the frequency separation of the initial solitons is
      studied both analytically and numerically. Depending on the value of the
      frequency detuning, if the two initial solitons are in phase (symmetric input),
      two bound solitons with equal amplitudes (breather), a single soliton, or a pair
      of solitons, which have equal amplitudes and exhibit opposite velocities, can be
      generated. When the two initial solitons are out-of-phase (antisymmetric input),
      only the last scenario takes place. Also, we calculated the threshold values of
      the frequency separation at which the structure of the emerging solitons changes.
      Moreover, we demonstrated that two of these critical frequencies correspond to
      cusplike maxima of the energy density of the radiative modes. Finally, we show
      that these analytical results are entirely verified by numerical simulations.

PMID- 11970353
TI  - Collapse arresting in an inhomogeneous quintic nonlinear Schrodinger model.
AB  - Collapse of (1+1)-dimensional beams in the inhomogeneous one-dimensional quintic
      nonlinear Schrodinger equation is analyzed both numerically and analytically. It
      is shown that in the vicinity of a narrow attractive inhomogeneity, the collapse
      of beams in which the homogeneous medium would blow up may be delayed and even
      arrested.

PMID- 11970354
TI  - Dispersive properties of finite, one-dimensional photonic band gap structures:
      applications to nonlinear quadratic interactions.
AB  - We discuss the linear dispersive properties of finite one-dimensional photonic
      band-gap structures. We introduce the concept of a complex effective index for
      structures of finite length, derived from a generalized dispersion equation that
      identically satisfies the Kramers-Kronig relations. We then address the
      conditions necessary for optimal, phase-matched, resonant second harmonic
      generation. The combination of enhanced density of modes, field localization, and
      exact phase matching near the band edge conspire to yield conversion efficiencies
      orders of magnitude higher than quasi-phase-matched structures of similar
      lengths. We also discuss an unusual and interesting effect: counterpropagating
      waves can simultaneously travel with different phase velocities, pointing to the
      existence of two dispersion relations for structures of finite length.

PMID- 11970355
TI  - Radiative transfer in chiral random media.
AB  - This paper is devoted to the investigation of polarization and radiative
      characteristics of coherent and diffused light beams in isotropic media with
      optically active particles. Simple solutions for the Stokes vectors of the direct
      and diffused beams are obtained in the framework of the vector radiative transfer
      theory. Results obtained can be used for the generalization of the circular
      dichroism and optical rotation dispersion spectroscopy for the case of disperse
      media.

PMID- 11970356
TI  - Scattering of dislocated wave fronts by vertical vorticity and the Aharonov-Bohm
      effect. I. Shallow water.
AB  - When a surface wave interacts with a vertical vortex in shallow water the latter
      induces a dislocation in the incident wave fronts that is analogous to what
      happens in the Aharonov-Bohm effect for the scattering of electrons by a confined
      magnetic field. In addition to this global similarity between these two physical
      systems there is scattering. This paper reports a detailed calculation of this
      scattering, which is quantitatively different from the electronic case in that a
      surface wave penetrates the inside of a vortex while electrons do not penetrate a
      solenoid. This difference, together with an additional difference in the
      equations that govern both physical systems, lead to a quite different scattering
      in the case of surface waves, whose main characteristic is a strong asymmetry in
      the scattering cross section. The assumptions and approximations under which
      these effects happen are carefully considered, and their applicability to the
      case of the scattering of acoustic waves by vorticity is noted.

PMID- 11970357
TI  - Scattering of dislocated wave fronts by vertical vorticity and the Aharonov-Bohm
      effect. II. Dispersive waves.
AB  - Previous results on the scattering of surface waves by vertical vorticity on
      shallow water are generalized to the case of dispersive water waves. Dispersion
      effects are treated perturbatively around the shallow water limit, to first order
      in the ratio of depth to wavelength. The dislocation of the incident wave front,
      analogous to the Aharonov-Bohm effect, is still observed. At short wavelengths
      the scattering is qualitatively similar to the nondispersive case. At moderate
      wavelengths, however, there are two markedly different scattering regimes
      according to whether the depth is smaller or larger than sqrt[3] times capillary
      length. In the latter case, dispersion and advection may compensate leading to a
      spiral interference pattern. The dislocation is characterized by a parameter that
      depends both on phase and group velocity. The validity range of the calculation
      is the same as in the shallow water case: wavelengths small compared to vortex
      radius, and low Mach number. The implications of these limitations are carefully
      considered.

PMID- 11970358
TI  - Extension of the mapped Fourier method to time-dependent problems.
AB  - A numerical method is described for integration of the time-dependent Schrodinger
      equation within the presence of a Coulomb field. Because of the singularity at
      r=0, the wave packet has to be represented on a grid with a high density of
      points near the origin; at the same time, because of the long-range character of
      the Coulomb potential, the grid must extend to large values of r. The sampling
      points are chosen, following E. Fattal, R. Baer, and R. Kosloff [Phys. Rev. E 53,
      1217 (1996)], using a classical phase space criterion. Following those workers,
      the unequally spaced grid points are mapped to an equally spaced grid, allowing
      use of fast Fourier transform propagation methods that scale as N ln N, where N
      is the number of grid points. As a first test, eigenenergies for the hydrogen
      atom are extracted from short-time segments of the electronic wave-packet
      autocorrelation function; high accuracy is obtained by using the filter
      diagonalization method. As a second test, the ionization rate of the hydrogen
      atom resulting from a half-cycle pulse is calculated. These results are in
      excellent agreement with earlier calculations.

PMID- 11970359
TI  - Evolving three-dimensional cellular automata to perform a quasiperiod-3
      collective behavior task.
AB  - We present results from experiments in which a genetic algorithm (GA) is used to
      develop three-dimensional cellular automata (CA) to perform a nontrivial
      collective behavior task. Under a fitness function that is defined as an averaged
      area in the iterative map, the GA detects a CA rule with quasiperiod-3 (QP3)
      collective behavior and another with period-3. For rules with QP3 the time
      autocorrelation function decays as a power law with an exponent of -1/2,
      according to the predictions of the Kardar-Parisi-Zhang equation, and a space
      time diagram reveals the existence of propagating structures inside the system.

PMID- 11970360
TI  - Active clusters in disordered systems.
AB  - We introduce an exact algorithm to calculate the distribution of large low energy
      clusters (droplets) in disordered manifolds and disordered magnets, and we
      analyze the extent to which these clusters can be treated as independent two
      level systems. We show that interfaces in randomly diluted networks always have
      broad droplet distributions, while diluted antiferromagnets in a field can have
      either power law or exponential droplet distributions.

PMID- 11970361
TI  - Reversible fluctuation rectifier.
AB  - The analysis of a Feynman's ratchet system [J. M. R. Parrondo and P. Espanol, Am.
      J. Phys. 64, 1125 (1996)] and of its electrical counterpart, a diode engine [I.
      M. Sokolov, Europhys. Lett. 44, 278 (1998)] has shown that "fluctuation
      rectifiers" consisting of a nonlinear element (ratchet, diode) and a linear
      element (vane, resistor) kept at different temperatures always show efficiency
      smaller than the Carnot value, thus indicating the irreversible mode of
      operation. We show that this irreversibility is not intrinsic for a system in
      simultaneous contact with two heat baths at different temperatures and that a
      fluctuation rectifier can work reversibly. This is illustrated by a model with
      two diodes switched in opposite directions, where the Carnot efficiency is
      achieved when backward resistivity of the diodes tends to infinity.

PMID- 11970362
TI  - Canonical phase-space approach to the noisy Burgers equation.
AB  - Presenting a general phase-space approach to stochastic processes we analyze in
      particular the Fokker-Planck equation for the noisy Burgers equation and discuss
      the time-dependent and stationary probability distributions. In one dimension we
      derive the long-time skew distribution approaching the symmetric stationary
      Gaussian distribution. In the short-time regime we discuss heuristically the
      nonlinear soliton contributions and derive an expression for the distribution in
      accordance with the directed polymer-replica model and asymmetric exclusion model
      results.

PMID- 11970363
TI  - Thermal noise can facilitate energy conversion by a ratchet system.
AB  - Molecular motors in biological systems are expected to use ambient fluctuation.
      In a recent paper [Phys. Rev. Lett. 80, 5251 (1998)], it was shown that the
      following question was unanswered: Can thermal noise facilitate energy conversion
      by ratchet system? We consider it using stochastic energetics, and show that
      there exist systems where thermal noise helps the energy conversion.

PMID- 11970365
TI  - Effects of time-delayed interactions on dynamic patterns in a coupled phase
      oscillator system.
AB  - We investigate the effects of time delayed interactions in the network of neural
      oscillators. We perform the stability analysis in the vicinity of a synchronized
      state at vanishing time delay and present a related phase diagram. In the
      simulations it is shown that time delay induces various phenomena such as
      clustering where the system is spontaneously split into two phase locked groups,
      synchronization, and multistability. Time delay effects should be considered both
      in the natural and artificial neural systems whose information processing is
      based on the spatiotemporal dynamic patterns.

PMID- 11970364
TI  - Nonuniform reaction rate distribution for the generalized Fisher equation:
      ignition ahead of the reaction front.
AB  - We have addressed the problem of wavefront propagation for the generalized Fisher
      equation involving diffusion transport with a finite velocity and a spatially
      nonuniform reaction rate. We have considered in detail the phenomenon of
      wavefront jump or ignition ahead of the reaction front for a piecewise constant
      reaction rate. By using a relativistic mechanics technique based on the principle
      of least action we have found the criterion under which the ignition phenomenon
      happens and the time of appearance of the new front ahead of the initial reaction
      front.

PMID- 11970366
TI  - Synchronization and coherence in thermodynamic coupled map lattices with
      intermediate-range coupling.
AB  - In spatially extended systems, intermediate-range interactions arise naturally in
      some physical contexts. To study them, we investigate a model of coupled map
      lattices (CML's) with intermediate-range coupling, and derive analytic conditions
      for its synchronization. We find that in these CML's, if the range of coupling is
      fixed, the law of large numbers applies for the mean field. The total normalized
      power in nonzero components of the power spectrum of the mean field goes to zero
      in the thermodynamic limit. We also show that in the same limit the relevant
      parameter for synchronization and coherence is the fraction of sites coupled, and
      not their number.

PMID- 11970367
TI  - Improved false nearest neighbor method to detect determinism in time series data.
AB  - The false nearest neighbor method introduced by Kennel et al. [Phys. Rev. A 45,
      3403 (1992)] is revisited and modified in order to ensure a correct distinction
      between low-dimensional chaotic data and noise. Still, correlated noise processes
      can yield vanishing percentages of false nearest neighbors for rather low
      embedding dimensions and can be mistaken for deterministic signals. Therefore,
      the false nearest neighbors method has always to be combined with a surrogate
      data test.

PMID- 11970368
TI  - Flow of a vortex-pair street and the evolution of salt fingers.
AB  - We considered the geometry of a double row of vortex pairs in an ideal fluid, and
      studied the evolution of salt fingers from the geometry systematically. This
      study illustrates the mechanism of the generation of large-scale convective cells
      at the final stage of the fingering instability. We discuss why in the growth of
      double-diffusive salt fingers the emergence of such large convection cells has
      been implicated phenomenologically as an onset to turbulence, terminating the
      finger growth.

PMID- 11970369
TI  - Diameters of vortex spirals in three-dimensional turbulence.
AB  - It has been proposed by a number of authors that fully developed turbulence
      contains spiral-like vorticity distributions that wrap up around strained vortex
      tubes, but numerical simulations seem to show otherwise. In the present paper, we
      suggest an explanation for the numerical results. Using stability considerations
      and numerical results for the Reynolds numbers of the most intense vortex tubes,
      we obtain an estimate for the characteristic diameter of the largest spirals as a
      function of the Reynolds number. We find that this diameter decreases rapidly,
      relative to the integral scale, as the Reynolds number tends to infinity.

PMID- 11970370
TI  - Pretransitional behavior above the nematic-isotropic phase transition of an
      auxetic trimer liquid crystal.
AB  - Static light scattering and electric field-induced Kerr measurements were
      performed above the nematic-isotropic phase transition of a terminal-lateral
      lateral-terminal negative Poisson ratio trimer. For both measurements the inverse
      susceptibility was observed to be nearly linear with temperature, a result
      inconsistent with our previously reported Kerr data [Phys. Rev. E 58, 2041
      (1998)].

PMID- 11970371
TI  - Classical-nonclassical crossover behavior of critical and noncritical liquid
      binary solutions in a strong electric field.
AB  - A nitrobenzene-dodecane binary mixture has been studied with the use of the
      nonlinear dielectric effect for one critical and two noncritical concentrations
      in a series of frequencies (f(m)) in a weak measuring electric field. It has been
      found that for the temperature region where 1/f(m)>tau (tau, the lifetime of
      fluctuations), the critical exponent psi=gamma-2beta approximately equal to 0.59
      and consequently exponents gamma (susceptibility) and beta (order parameter)
      exhibit nonclassical values. Close to the phase-transition temperature where
      1/f(m)<tau, different patterns appear for critical and noncritical
      concentrations. For the latter the exponent psi tends to zero that may point to
      the classical behavior, with gamma approximately equal to 1 and beta-->0.5. For
      the critical concentration psi approximately equal to 0.4, this may be the
      consequence of the semiclassical behavior with gamma approximately equal to 1 and
      beta approximately equal to 0.325.

PMID- 11970372
TI  - Stochastic hierarchical model for cluster-cluster aggregation.
AB  - A stochastic hierarchical model of cluster-cluster aggregation, which is obtained
      by introducing a sticking probability into the recently proposed hierarchical
      model by Sornsen and Oh [Phys. Rev. E 58, 7545 (1998)], is presented. The fractal
      dimension and aspect ratio calculated using the model give good agreement with
      those obtained in standard simulations of cluster-cluster aggregates. An
      interesting result is that the fractal dimension shows a peak as a function of
      the sticking probability.

PMID- 11970373
TI  - Ionization, electron attachment, and drift in CHF3.
AB  - Using a pulsed Townsend technique, we have measured the effective ionization
      coefficient and the electron drift velocities in CHF(3). The density-normalized
      electric field intensity E/N ranged from 4 to 250 townsends (Td) (1 Td=10(-17) V
      cm(2)). The E/N value at which the effective ionization coefficient becomes zero
      was estimated to be 66 Td. For E/N<20 Td, the electron attachment coefficients
      are practically constant, and are compatible to within about +/-70% with
      previously measured values at thermal energies and above.

PMID- 11970374
TI  - Glassy dynamics and aging in an exactly solvable spin model.
AB  - We introduce a simple two-dimensional spin model with short-range interactions
      which shows glassy behavior despite a Hamiltonian which is completely homogeneous
      and possesses no randomness. We solve exactly for both the static partition
      function of the model and the distribution of energy barriers, giving us the
      equilibration time scales at low temperature. Simulations of instantaneous
      quenches and of annealing of the model are in good agreement with the analytic
      calculations. We also measure the two-time spin correlation as a function of
      waiting time, and show that the model has aging behavior consistent with the
      distribution of barrier heights. The model appears to have no sharp glass
      transition. Instead, it falls out of equilibrium at a temperature which decreases
      logarithmically as a function of the cooling time.

PMID- 11970375
TI  - Theory of spiral wave dynamics in weakly excitable media: asymptotic reduction to
      a kinematic model and applications.
AB  - In a weakly excitable medium, characterized by a large threshold stimulus, the
      free end of an isolated broken plane wave (wave tip) can either rotate (steadily
      or unsteadily) around a large excitable core, thereby producing a spiral pattern,
      or retract, causing the wave to vanish at boundaries. An asymptotic analysis of
      spiral motion and retraction is carried out in this weakly excitable large core
      regime starting from the free-boundary limit of the reaction-diffusion models,
      valid when the excited region is delimited by a thin interface. The wave
      description is shown to naturally split between the tip region and a far region
      that are smoothly matched on an intermediate scale. This separation allows us to
      rigorously derive an equation of motion for the wave tip, with the large scale
      motion of the spiral wave front slaved to the tip. This kinematic description
      provides both a physical picture and exact predictions for a wide range of wave
      behavior, including (i) steady rotation (frequency and core radius), (ii) exact
      treatment of the meandering instability in the free-boundary limit with the
      prediction that the frequency of unstable motion is half the primary steady
      frequency, (iii) drift under external actions (external field with application to
      axisymmetric scroll ring motion in three dimensions, and spatial- or/and time
      dependent variation of excitability), and (iv) the dynamics of multiarmed spiral
      waves with the prediction that steadily rotating waves with two or more arms are
      linearly unstable. Numerical simulations of FitzHugh-Nagumo kinetics are used to
      test several aspects of our results. In addition, we discuss the semiquantitative
      extension of this theory to finite cores and pinpoint mathematical subtleties
      related to the thin interface limit of singly diffusive reaction-diffusion
      models.

PMID- 11970376
TI  - Exact solution of a Z(4) gauge Potts model on planar lattices.
AB  - The exact solution of a general Z(4) gauge Potts model with a single and double
      plaquette representation of the action is found on a subspace of gauge-coupling
      parameters on the square and triangular lattices. The two Ising-type critical
      lines of a second-order phase transition for the model on a square lattice are
      found. For the model on a triangular lattice the two critical surfaces of an
      Ising-type and two nontrivial lines of a second-order phase transition with
      different critical behavior than on the critical surfaces are found. It is shown
      that a two-dimensional (2D) general Z(4) gauge Potts model with single and double
      plaquette representation of the action and a 2D spin-3 / 2 Ising model belong to
      the same universality class.

PMID- 11970377
TI  - Scale invariance and invariant scaling in a mixed hierarchical system.
AB  - We consider a mixed hierarchical model with heterogeneous and monotone conditions
      of destruction. We investigate how scaling properties of defects in the model are
      related with heterogeneity of rules of destruction, determined by concentration
      of the mixture. The system demonstrates different kinds of criticality as a
      general form of system behavior. The following forms of critical behavior are
      obtained: stability, catastrophe, scale invariance, and invariant scaling.
      Different slopes of the magnitude-frequency relation are realized in areas of
      critical stability and catastrophe. A simple relation between the slope of
      magnitude-frequency relation and parameters of the mixture is established.

PMID- 11970378
TI  - Relation between fractal dimension and roughness index for fractal surfaces.
AB  - This paper discusses the relation between fractal dimension and roughness index
      for fractal surfaces of solids. The applicability of the relation to fracture of
      Mode III+Mode I complex loading is shown. The applicability to other rough
      surfaces is discussed.

PMID- 11970379
TI  - Pair contact process in two dimensions.
AB  - We study the stationary properties of the two-dimensional pair contact process, a
      nonequilibrium lattice model exhibiting a phase transition to an absorbing state
      with an infinite number of configurations. The critical probability and static
      critical exponents are determined via Monte Carlo simulations, as well as order
      parameter moment ratios and the scaling of the initial density decay. The static
      critical properties fall in the directed percolation universality class.

PMID- 11970380
TI  - Theoretical model of diatomic molecules interacting on a two-dimensional lattice.
AB  - The coverage-dependent binding energy of interacting dimers is investigated using
      the lattice gas model. Dimers with distinguishable ends are assumed to interact
      if they occupy only nearest-neighbor lattice sites. The interaction energy
      between a pair of dimers will be repulsive if identical ends are in nearest
      neighbor positions and attractive if they are not. The grand partition function
      is derived by using the Bethe approximation. The energy of the system of
      interacting dimers is evaluated as a function of the lattice coverage at
      different temperatures and pair interaction potentials. Under the same conditions
      the average number of all types of nearest-neighbors is evaluated.

PMID- 11970381
TI  - Calculation of ground states of four-dimensional +/-J Ising spin glasses.
AB  - Ground states of four-dimensional (d=4) Edwards-Anderson Ising spin glasses are
      calculated for sizes up to 7 x 7 x 7 x 7 using a combination of a genetic
      algorithm and cluster-exact approximation. The ground-state energy of the
      infinite system is extrapolated as e0(infinity)=-2.095(1). The ground-state
      stiffness (or domain wall) energy Delta is calculated. A delta approximately
      L(theta(S)) behavior with theta(S)=0.64(5) is found which confirms that the d=4
      model has an equilibrium spin-glass-paramagnet transition for nonzero T(c).

PMID- 11970382
TI  - Metastable states of an Ising-like thermally bistable system.
AB  - The lifetimes of the metastable states are investigated in an Ising-like model
      associated with thermally bistable systems. A discrete mesoscopic Markovian
      dynamic is established using an optimized version of the previously presented
      Monte Carlo entropic sampling method. This is well suited to an extensive study
      of the role of the physical parameters: temperature, interaction parameter,
      electronic energy gap. By combining a discrete Markovian mesoscopic dynamic and
      the absorbing Markov chain technique, we obtain an analytical access to the
      average lifetime of the metastable state. One-variable and two-variable
      approximations for the original microscopic master equation are presented and
      discussed. A typical difference in the thermal dependence of the lifetime of the
      low- and the high-temperature metastable states is found, and explained as a
      consequence of the temperature-dependent field associated with the Ising-like
      model. The validity, the advantages, and the limits of the method are discussed,
      as well as the possible consequences on the behavior of spin transition systems.
      A prospective for a possible phenomenological finite-size scaling is presented.

PMID- 11970383
TI  - Evolution of speckle during spinodal decomposition.
AB  - Time-dependent properties of the speckled intensity patterns created by
      scattering coherent radiation from materials undergoing spinodal decomposition
      are investigated by numerical integration of the Cahn-Hilliard-Cook equation. For
      binary systems which obey a local conservation law, the characteristic domain
      size is known to grow in time tau as R=[Btau](n) with n=1/3, where B is a
      constant. The intensities of individual speckles are found to be nonstationary,
      persistent time series. The two-time intensity covariance at wave vector k can be
      collapsed onto a scaling function Cov(deltat,t), where deltat=k(1/n)B(tau(2)
      tau(1)) and t=k(1/n)B(tau(1)+tau(2))/2. Both analytically and numerically, the
      covariance is found to depend on deltat only through deltat/t in the small-t
      limit and deltat/t (1-n) in the large-t limit, consistent with a simple theory of
      moving interfaces that applies to any universality class described by a scalar
      order parameter. The speckle-intensity covariance is numerically demonstrated to
      be equal to the square of the two-time structure factor of the scattering
      material, for which an analytic scaling function is obtained for large t. In
      addition, the two-time, two-point order-parameter correlation function is found
      to scale as C(r/(B(n)sqaureroot[tau1(2n)+tau2(2n)]),tau1/tau2), even for quite
      large distances r. The asymptotic power-law exponent for the autocorrelation
      function is found to be lambda approximately 4.47, violating an upper bound
      conjectured by Fisher and Huse.

PMID- 11970384
TI  - Critical adsorption near edges.
AB  - Symmetry breaking surface fields give rise to nontrivial and long-ranged order
      parameter profiles for critical systems such as fluids, alloys, or magnets
      confined to wedges. We discuss the properties of the corresponding universal
      scaling functions of the order parameter profile and the two-point correlation
      function, and determine the critical exponents eta(parallel) and eta(
      perpendicular) for the so-called normal transition.

PMID- 11970385
TI  - Numerical evidence for divergent Burnett coefficients.
AB  - In previous papers [Phys. Rev. A 41, 4501 (1990); Phys. Rev. E 18, 3178 (1993)],
      simple equilibrium expressions were obtained for nonlinear Burnett coefficients.
      A preliminary calculation of a 32-particle Lennard-Jones fluid was presented in
      the previous papers. Now, sufficient resources have become available to address
      the question of whether nonlinear Burnett coefficients are finite for soft
      spheres. The hard sphere case is known to have infinite nonlinear Burnett
      coefficients (i.e., a nonanalytic constitutive relation) from mode-coupling
      theory. This paper reports a molecular dynamics caclulation of the third order
      nonlinear Burnett coefficient of a Lennard-Jones fluid undergoing color flow,
      which indicates that this term diverges in the thermodynamic limit.

PMID- 11970386
TI  - Oscillatory behavior in a lattice prey-predator system.
AB  - Using Monte Carlo simulations we study a lattice model of a prey-predator system.
      We show that in the three-dimensional model populations of preys and predators
      exhibit coherent periodic oscillations but such a behavior is absent in lower
      dimensional models. Finite-size analysis indicate that amplitude of these
      oscillations is finite even in the thermodynamic limit. This is an example of a
      microscopic model with stochastic dynamics which exhibits oscillatory behavior
      without any external driving force. We suggest that oscillations in our model are
      induced by some kind of stochastic resonance.

PMID- 11970387
TI  - Thermodynamics of a two-dimensional unbounded self-gravitating system.
AB  - The thermodynamics of a two-dimensional self-gravitating system occupying the
      whole plane is considered in the mean-field approximation. First, it is proven
      that, if the number N of particles and the total energy E are imposed as the only
      external constraints, then the entropy admits the least upper bound
      S+(N,E)=2E/N+N ln(epi(2)) (in appropriate units). Moreover, there does exist a
      unique state of maximum entropy, which is characterized by a Maxwellian
      distribution function with a temperature T=N/2 independent of E. Next, it is
      shown that, if the total angular momentum J is imposed as a further constraint,
      the largest possible value of the entropy does not change, and there is no
      admissible state of maximum entropy, but in the case J=0. Finally, some
      inequalities satisfied by a class of so-called H functions and related
      generalized entropies are given.

PMID- 11970388
TI  - Correlation functions in the two-dimensional random-field Ising model.
AB  - Transfer-matrix methods are used to study the probability distributions of spin
      spin correlation functions G in the two-dimensional random-field Ising model, on
      long strips of width L=3-15 sites, for binary field distributions at generic
      distance R, temperature T, and field intensity h(0). For moderately high T, and
      h(0) of the order of magnitude used in most experiments, the distributions are
      singly peaked, though rather asymmetric. For low temperatures the single-peaked
      shape deteriorates, crossing over towards a double-delta ground-state structure.
      A connection is obtained between the probability distribution for correlation
      functions and the underlying distribution of accumulated field fluctuations.
      Analytical expressions are in good agreement with numerical results for R/L > or
      approximately 1, low T, h(0) not too small, and near G=1. From a finite-size
      ansatz at T=T(c)(h(0)=0), h(0)-->0, averaged correlation functions are predicted
      to scale with L(y)h(0), y=7/8. From numerical data we estimate y=0.875+/-0.025,
      in excellent agreement with theory. In the same region, the rms relative width W
      of the probability distributions varies for fixed R/L=1 as W approximately
      h(kappa)(0) f(L h(u)(0)) with kappa approximately 0.45, u approximately 0.8; f(x)
      appears to saturate when x-->infinity, thus implying W approximately h(kappa)(0)
      in d=2.

PMID- 11970389
TI  - Universality in the off-equilibrium critical dynamics of the three-dimensional
      diluted Ising model.
AB  - We study the off-equilibrium critical dynamics of the three-dimensional diluted
      Ising model. We compute the dynamical critical exponent z and we show that it is
      independent of the dilution only when we take into account the scaling
      corrections to the dynamics. Finally, we will compare our results with the
      experimental data.

PMID- 11970390
TI  - Depinning transition and thermal fluctuations in the random-field Ising model.
AB  - We analyze the depinning transition of a driven interface in the three
      dimensional (3D) random field Ising model (RFIM) with quenched disorder by means
      of Monte Carlo simulations. The interface initially built into the system is
      perpendicular to the [111] direction of a simple cubic lattice. We introduce an
      algorithm which is capable of simulating such an interface independent of the
      considered dimension and time scale. This algorithm is applied to the 3D RFIM to
      study both the depinning transition and the influence of thermal fluctuations on
      this transition. It turns out that in the RFIM characteristics of the depinning
      transition depend crucially on the existence of overhangs. Our analysis yields
      critical exponents of the interface velocity, the correlation length, and the
      thermal rounding of the transition. We find numerical evidence for a scaling
      relation for these exponents and the dimension d of the system.

PMID- 11970391
TI  - Harmonic potential driven by long-range correlated noise.
AB  - The probability distribution of a particle in a quadratic potential driven by
      Gaussian long-range correlated noise has been obtained. The long-time asymptotic
      relaxation of the stochastic process has been characterized in terms of the long
      range correlated noise appearing in the corresponding stochastic differential
      equation defining the process. The particular case when the particle is driven by
      a Gaussian color noise has also been revisited, in this way giving its exact
      probability distribution for all time. By using a characteristic functional
      technique reported previously, results for a non-Gaussian long-range correlated
      noise are also shown. Emphasis has been placed on solving the plane rotator in
      the presence of arbitrary random torques having long-range correlations. In order
      to show strong and weak non-Markovian effects coming from different sources of
      noise, the undamped free particle under the influence of arbitrary accelerations
      has been analyzed. We also analyze in detail the structure of the trajectories of
      the overdamped and undamped free particle.

PMID- 11970392
TI  - Models of competitive learning: complex dynamics, intermittent conversions, and
      oscillatory coarsening.
AB  - We present two models of competitive learning, which are respectively interfacial
      (i.e., where the interiors of domains are unaffected by the rules of the model)
      and cooperative (i.e., where the bulk as well as the interface of an individual
      domain is governed by the rules of the model) learning. This learning is outcome
      related, so that spatially and temporally local environments influence the
      conversion of a given site between one of two different types. We focus here on
      the behavior of the models at coexistence, which yields critical behavior and the
      existence of a phase involving a type of coarsening which is oscillatory in
      nature. In the discussion we speculate on, among other issues, the likely
      behavior of the models away from coexistence.

PMID- 11970394
TI  - Metastable states in spin glasses and disordered ferromagnets.
AB  - We study analytically M-spin-flip stable states in disordered short-ranged Ising
      models (spin glasses and ferromagnets) in all dimensions and for all M. Our
      approach is primarily dynamical, and is based on the convergence of sigma(t), a
      zero-temperature dynamical process with flips of lattice animals up to size M and
      starting from a deep quench, to a metastable limit sigma(infinity). The results
      (rigorous and nonrigorous, in infinite and finite volumes) concern many aspects
      of metastable states: their numbers, basins of attraction, energy densities,
      overlaps, remanent magnetizations, and relations to thermodynamic states. For
      example, we show that their overlap distribution is a delta function at zero. We
      also define a dynamics for M=infinity, which provides a potential tool for
      investigating ground state structure.

PMID- 11970393
TI  - Speed of wave-front solutions to hyperbolic reaction-diffusion equations.
AB  - The asymptotic speed problem of front solutions to hyperbolic reaction-diffusion
      (HRD) equations is studied in detail. We perform linear and variational analyses
      to obtain bounds for the speed. In contrast to what has been done in previous
      work, here we derive upper bounds in addition to lower ones in such a way that we
      can obtain improved bounds. For some functions it is possible to determine the
      speed without any uncertainty. This is also achieved for some systems of HRD
      (i.e., time-delayed Lotka-Volterra) equations that take into account the
      interaction among different species. An analytical analysis is performed for
      several systems of biological interest, and we find good agreement with the
      results of numerical simulations as well as with available observations for a
      system discussed recently.

PMID- 11970395
TI  - Angle-angular-momentum entropic bounds and optimal entropies for quantum
      scattering of spinless particles.
AB  - In this paper the angle-angular-momentum entropic lower and upper bounds are
      proved by using Tsallis-like entropies, the Riesz theorem, and the Lagrange
      multiplier method for the quantum scattering of the spinless particles. A
      connection between optimal states and the most stringent entropic bounds on
      Tsallis-like entropies in the quantum scattering is established. The results of
      experimental tests of the state-independent angle-angular-momentum entropic
      bounds as well as of the stringent entropic optimal bounds in pion-nucleus
      scattering are obtained by calculations of the scattering entropies from the
      experimental available pion-nucleus phase shifts. Comparisons of these results
      with predictions of the principle of minimum distance in the space of states are
      presented. Then it is shown that experimental pion-nucleus entropies are well
      described by optimal entropies, and that the experimental data are consistent
      with the principle of minimum distance in the space of scattering states.

PMID- 11970396
TI  - Statistical mechanics of nonrelativistic charged particles in a constant magnetic
      field.
AB  - The statistical mechanics of a system of nonrelativistic charged particles in a
      constant magnetic field is discussed. The spatial dimension D is arbitrary, with
      D>or=3 assumed. Calculations are presented from first principles using the
      effective action method. For D>or=5 the system has a phase transition with a Bose
      condensate. We show how the effective action method deals in a very natural way
      with the condensate, and study its role in the magnetization of the gas. For
      large values of the magnetic field we show how the magnetized gas in D spatial
      dimensions behaves like the free Bose gas in D-2 spatial dimensions. Even though
      for D=3 the magnetized gas does not have a phase transition for any nonzero value
      of the magnetic field, we show how the specific heat starts to resemble the
      result for the free gas as the magnetic field is reduced. A number of analytical
      approximations for the magnetization and specific heat are given, and compared
      with numerical results. In this way we are able to study in precise detail how
      the B-->0 limit of the magnetized gas is achieved.

PMID- 11970398
TI  - Exactly soluble hierarchical clustering model: inverse cascades, self-similarity,
      and scaling.
AB  - We show how clustering as a general hierarchical dynamical process proceeds via a
      sequence of inverse cascades to produce self-similar scaling, as an intermediate
      asymptotic, which then truncates at the largest spatial scales. We show how this
      model can provide a general explanation for the behavior of several models that
      has been described as "self-organized critical," including forest-fire, sandpile,
      and slider-block models.

PMID- 11970397
TI  - Nonuniversality of compact support probability distributions in random matrix
      theory.
AB  - The two-point resolvent is calculated in the large-n limit for the generalized
      fixed and bounded trace ensembles. It is shown to disagree with that of the
      canonical Gaussian ensemble by a nonuniversal part that is given explicitly for
      all monomial potentials V(M)=M(2p). Moreover, we prove that for the generalized
      fixed and bounded trace ensemble all k-point resolvents agree in the large-n
      limit, despite their nonuniversality.

PMID- 11970399
TI  - Phase diagram of the Biham-Middleton-Levine traffic model in three dimensions.
AB  - We study numerically the behavior of the Biham-Middleton-Levine traffic model in
      three dimensions. Our extensive numerical simulations show that the phase diagram
      for this model in three dimensions is markedly different from that in one and two
      dimensions. In addition to the full speed moving as well as the completely
      jamming phases, whose respective average asymptotic car speeds (v) equal one and
      zero, we observe an extensive region of car densities rho with a low but nonzero
      average asymptotic car speed. The transition from this extensive low average
      asymptotic car speed region to the completely jamming region is at least second
      order. We argue that this low speed region is a result of the formation of a
      spatially limited-extended percolating cluster. Thus, this low speed phase is
      present in the (n>3)-dimensional Biham-Middleton-Levine model as well.

PMID- 11970400
TI  - Scaling of the distribution of fluctuations of financial market indices.
AB  - We study the distribution of fluctuations of the S&P 500 index over a time scale
      deltat by analyzing three distinct databases. Database (i) contains approximately
      1 200 000 records, sampled at 1-min intervals, for the 13-year period 1984-1996,
      database (ii) contains 8686 daily records for the 35-year period 1962-1996, and
      database (iii) contains 852 monthly records for the 71-year period 1926-1996. We
      compute the probability distributions of returns over a time scale deltat, where
      deltat varies approximately over a factor of 10(4)-from 1 min up to more than one
      month. We find that the distributions for deltat<or= 4 d (1560 min) are
      consistent with a power-law asymptotic behavior, characterized by an exponent
      alpha approximately 3, well outside the stable Levy regime 0<alpha<2. To test the
      robustness of the S&P result, we perform a parallel analysis on two other
      financial market indices. Database (iv) contains 3560 daily records of the NIKKEI
      index for the 14-year period 1984-1997, and database (v) contains 4649 daily
      records of the Hang-Seng index for the 18-year period 1980-1997. We find
      estimates of alpha consistent with those describing the distribution of S&P 500
      daily returns. One possible reason for the scaling of these distributions is the
      long persistence of the autocorrelation function of the volatility. For time
      scales longer than (deltat)x approximately 4 d, our results are consistent with a
      slow convergence to Gaussian behavior.

PMID- 11970401
TI  - Enhanced pulse propagation in nonlinear arrays of oscillators.
AB  - The propagation of a pulse in a nonlinear array of oscillators is influenced by
      the nature of the array and by its coupling to a thermal environment. For
      example, in some arrays a pulse can be speeded up while in others a pulse can be
      slowed down by raising the temperature. We begin by showing that an energy pulse
      (one dimension) or energy front (two dimensions) travels more rapidly and remains
      more localized over greater distances in an isolated array (microcanonical) of
      hard springs than in a harmonic array or in a soft-springed array. Increasing the
      pulse amplitude causes it to speed up in a hard chain, leaves the pulse speed
      unchanged in a harmonic system, and slows down the pulse in a soft chain.
      Connection of each site to a thermal environment (canonical) affects these
      results very differently in each type of array. In a hard chain the dissipative
      forces slow down the pulse while raising the temperature speeds it up. In a soft
      chain the opposite occurs: the dissipative forces actually speed up the pulse,
      while raising the temperature slows it down. In a harmonic chain neither
      dissipation nor temperature changes affect the pulse speed. These and other
      results are explained on the basis of the frequency vs energy relations in the
      various arrays.

PMID- 11970402
TI  - Levy random walks with fluctuating step number and multiscale behavior.
AB  - Random walks with step number fluctuations are examined in n dimensions for when
      step lengths comprising the walk are governed by stable distributions, or by
      random variables having power-law tails. When the number of steps taken in the
      walk is large and uncorrelated, the conditions of the Levy-Gnedenko
      generalization of the central limit theorem obtain. When the number of steps is
      correlated, infinitely divisible limiting distributions result that can have Levy
      like behavior in their tails but can exhibit a different power law at small
      scales. For the special case of individual steps in the walk being Gaussian
      distributed, the infinitely divisible class of K distributions result. The
      convergence to limiting distributions is investigated and shown to be ultraslow.
      Random walks formed from a finite number of steps modify the behavior and
      naturally produce an inner scale. The single class of distributions derived have
      as special cases, K distributions, stable distributions, distributions with power
      law tails, and those characteristic of high and low frequency cascades. The
      results are compared with cellular automata simulations that are claimed to be
      paradigmatic of self-organized critical systems.

PMID- 11970403
TI  - Vortex dynamics and entropic forces in antiferromagnets and antiferromagnetic
      Potts models.
AB  - It is well known in models with an interface representation, such as the dimer
      model, the triangular Ising antiferromagnet, the six-vertex ice model, and the
      three-state antiferromagnetic Potts model on the square lattice, that topological
      defects of opposite charge are attracted with an entropically-driven Coulomb
      force. We examine the Potts model in detail, show explicitly how this force is
      felt through local fields, and calculate the defects' mobility. We then take two
      approaches to measuring this force numerically. First, we quench a random initial
      state to zero temperature and measure the density of defects rho(t) as a function
      of time. While this gives some evidence for a local force, we compare it with a
      free diffusion experiment, and show that the asymptotic decay of rho(t) depends
      on the initial distribution of defects rather than the forces between them.
      Second, we set up initial conditions with a single pair of vortices, and measure
      the force between them as a function of distance. This gives reasonable agreement
      with theory, although finite-size effects and a lack of ergodicity play a
      significant role.

PMID- 11970404
TI  - Finite-connectivity systems as error-correcting codes.
AB  - We investigate the performance of parity check codes using the mapping onto Ising
      spin systems proposed by Sourlas [Nature (London) 339, 693 (1989); Europhys.
      Lett. 25, 159 (1994)]. We study codes where each parity check comprises products
      of K bits selected from the original digital message with exactly C checks per
      message bit. We show, using the replica method, that these codes saturate
      Shannon's coding bound for K-->infinity when the code rate K/C is finite. We then
      examine the finite temperature case to assess the use of simulated annealing
      methods for decoding, study the performance of the finite K case, and extend the
      analysis to accommodate different types of noisy channels. The connection between
      statistical physics and belief propagation decoders is discussed and the dynamics
      of the decoding itself is analyzed. Further insight into new approaches for
      improving the code performance is given.

PMID- 11970405
TI  - Competitive dynamics in a three-dimensional Ising model.
AB  - We consider a three-dimensional ferromagnetic Ising model on a cubic lattice in
      contact with a heat bath at temperature T. The states of the system evolve in
      time according to two stochastic processes: the one-spin-flip Glauber dynamics
      where the order parameter is not conserved, and the two-spin-exchange Kawasaki
      kinetics, which conserves the order parameter. The former process mimics an input
      of energy into the system. Monte Carlo simulations were employed to determine the
      phase diagram for the stationary states of the model, and the corresponding
      critical exponents. Similarly to the observed for the related two-dimensional
      ferromagnetic Ising model, the phase diagram obtained exhibits the phenomenon of
      self-organization. Although the stationary states are mainly ferromagnetic at low
      temperatures, an antiferromagnetic phase appears for extremely high values of the
      flux of energy. Unlike the ferromagnetic case, the region of the phase diagram
      occupied by the antiferromagnetic phase is now larger. The determined critical
      exponents for this nonequilibrium model are in agreement with the well-known
      accepted values for the three-dimensional equilibrium Ising model.

PMID- 11970406
TI  - Wigner surmise for high-order level spacing distributions of chaotic systems.
AB  - We suggest an extension of the Wigner surmise for the nearest-neighbor-spacing
      distribution of energy levels of chaotic systems to include the nth-order spacing
      distributions. The main assumption is that the conditional probability density of
      occurrence of a level at a given distance from a fixed level, provided that this
      distance contains n levels, is expressed in terms of the (n+1)th power of
      corresponding probability for a distance containing no levels. At large spacings,
      the nth-order level distributions are assumed to have a Gaussian shape as in the
      cases covered by the Wigner surmise. The expressions obtained are in good
      agreement with the results of numerical calculation by means of the random matrix
      theory for the three universal classes of symmetry.

PMID- 11970407
TI  - Nonintegrable dynamics of the triplet-triplet spatiotemporal interaction.
AB  - In this paper we examine the coupling of two wave triplets sharing two common
      modes. The analysis is performed in the solitonic sector of the parameter space
      where uncoupled solutions departing from linearly unstable homogeneous initial
      conditions evolve into a collection of regularly interspersed, spatiotemporally
      localized spikes. The uncoupled system is integrable, but coupling destroys
      integrability. As coupling grows, energy transfer to smaller spatial scales does
      appear and becomes faster not only in linearly unstable, but also in linearly
      stable cases. Chaos in low-dimensional subsystems appears to be responsible for
      the transfer. We perform a series of numerical tests to verify this idea.

PMID- 11970408
TI  - Approach to Gaussian stochastic behavior for systems driven by deterministic
      chaotic forces.
AB  - We consider skew-product dynamical systems that describe the stroboscopic
      dynamics of a damped particle subjected to a chaotic kick force. In a suitable
      scaling limit the dynamics converges to the Ornstein-Uhlenbeck process. We
      investigate the deterministic chaotic corrections in the vicinity of this
      Gaussian limit case for various examples of chaotic forces. We present numerical
      evidence that, for certain classes of chaotic forces, the deterministic chaotic
      corrections of the invariant density are universal. We provide analytical results
      for forces generated by Tchebyscheff maps and sketch a renormalization group
      theory in the space of probability densities.

PMID- 11970409
TI  - Experimental observation of a torus-doubling transition to chaos near the
      ferroelectric phase transition of a KH2PO4 crystal.
AB  - A ferroelectric KH2PO4 crystal is implemented in a simple series connection of an
      RLC circuit and the transition to chaos near the phase-transition temperature is
      investigated. The torus-doubling scenario to chaos, the theory of which was
      expounded by Kaneko for high-dimensional dynamical systems, has been found in the
      crystal. These experimental results suggest that observation of the nonlinear
      dynamical behavior in condensed matter can give much information about the
      correlation between the generation of nonlinearity and the order-parameter
      dynamics of the crystal near the phase-transition temperature.

PMID- 11970410
TI  - Emergence of on-off intermittency in systems nonlinearly coupled to a
      nonequilibrium bath.
AB  - Approximate analytic solutions are presented for the dynamics of a classical
      oscillator nonlinearly coupled to a nonequilibrium bath. It is shown that as a
      result of the combined effect of the nonlinear coupling, which leads to nonlinear
      friction and multiplicative noise in the description of the reduced system, and
      the nonthermal properties of the reservoir, which give a specific self-sustained
      character to the coarse-grained oscillator, on-off intermittency can occur.
      Properties of this phenomenon, such as the universality in the length
      distribution of the laminar phase and the qualitative changes caused by the
      presence of additive noise, can be traced back to characteristics of the starting
      microscopic model.

PMID- 11970411
TI  - Rapid decoherence in integrable systems: a border effect.
AB  - We show that rapid decoherence, usually associated with chaotic dynamics, is not
      necessarily a hallmark of nonintegrability: border effects in integrable systems
      may produce similarly drastic decoherence rates. These can be found when the
      subsystem under observation possesses an energy limitation as, e.g., in the N
      atom Jaynes-Cummings model. We show for this model that special initial coherent
      wave packets exhibit entropy production rates strikingly similar to the chaotic
      case. Also, a (de)localization phenomenon is found to be a function of the
      proximity to the phase-space border.

PMID- 11970412
TI  - Approximate renormalization-group transformation for Hamiltonian systems with
      three degrees of freedom.
AB  - We construct an approximate renormalization transformation that combines
      Kolmogorov-Arnol'd-Moser and renormalization-group techniques, to analyze
      instabilities in Hamiltonian systems with three degrees of freedom. This scheme
      is implemented both for isoenergetically nondegenerate and for degenerate
      Hamiltonians. For the spiral mean frequency vector, we find numerically that the
      iterations of the transformation on nondegenerate Hamiltonians tend to degenerate
      ones on the critical surface. As a consequence, isoenergetically degenerate and
      nondegenerate Hamiltonians belong to the same universality class, and thus the
      corresponding critical invariant tori have the same type of scaling properties.
      We numerically investigate the structure of the attracting set on the critical
      surface and find that it is a strange nonchaotic attractor. We compute exponents
      that characterize its universality class.

PMID- 11970413
TI  - Analysis of the bifurcation diagram of a hybrid bistable system with feedback
      controls of chaos.
AB  - Based on the dynamic equation of a hybrid bistable system with a delayed
      feedback, we have studied changes of the bifurcation diagram of its output
      oscillation under chaos suppression and delayed feedback control of chaos,
      respectively, and the physical origin of these changes. The result clearly shows
      that, in this case, the input intensity of the system is replaced by a smaller
      effective input intensity. So the bifurcation diagram is shifted to its right
      side, and a certain part of the chaotic oscillation becomes periodic oscillation.

PMID- 11970414
TI  - Control of chaotic spatiotemporal spiking by time-delay autosynchronization.
AB  - A global time-delayed feedback control is applied to a globally coupled reaction
      diffusion system describing charge transport in a bistable semiconductor. We
      demonstrate that a variety of spatiotemporal unstable periodic orbits (UPOs)
      embedded in a chaotic attractor of the spatially extended system can be
      stabilized using an extended time-delay autosynchronization algorithm. These UPOs
      correspond to spiking current filaments. We critically evaluate analytical
      approximations for the limits of control originally developed for low-dimensional
      temporal chaos and show that the delay time can be extrapolated with high
      accuracy, while the theoretical limit for the control of UPOs in terms of the
      product of the period and the largest Lyapunov exponent is not reached. If the
      global feedback is modified by a spatial filter, we achieve stabilization of
      different spatial patterns.

PMID- 11970415
TI  - Multiple forms of intermittency in partial differential equation dynamo models.
AB  - We find concrete evidence for the presence of crisis-induced and Pomeau
      Manneville type-I intermittencies in an axisymmetric partial differential
      equation (PDE) mean-field dynamo model. These findings are of potential
      importance for two different reasons. First, as far as we are aware, this is the
      first time detailed evidence has been produced for the occurrence of these types
      of intermittency for such deterministic PDE models. And second, despite the
      rather idealized nature of these models, the concrete evidence for the occurrence
      of more than one type of intermittency in such models makes it in principle
      possible that different types of intermittency may occur in different solar-type
      stars or even in the same star over different epochs. In this way a multiple
      intermittency framework may turn out to be of importance in understanding the
      mechanisms responsible for grand-minima type behavior in the Sun and solar-type
      stars and in particular in the interpretation of the corresponding observational
      and proxy evidence.

PMID- 11970416
TI  - Sign-independent synchronization in unidirectionally coupled chaotic systems.
AB  - In this paper, a synchronization scheme independent of the sign of the driving
      signal is developed and analyzed. The corresponding synchronization phenomenon is
      termed sign-independent synchronization in this context. In our coupling scheme,
      an even coupling function is used at the response in an attempt to make the
      response independent of the sign of the driving signal. Furthermore, the Jacobian
      (and hence the stability) defined on the synchronization manifold of sign
      independent synchronization systems can be made identical to that of a
      corresponding active-passive decomposition system. Hence the conditions for
      achieving stable sign-independent synchronization can be generally established as
      a trivial case in unidirectionally coupled chaotic systems where the method of
      active-passive decomposition is applicable. Through numerical experiments
      performed on both continuous and discrete systems, we demonstrate that in-phase
      synchronization can be maintained even if the phase of the driving signal is
      randomly inverted. We believe the proposed chaotic synchronization will find
      important application in digital communications.

PMID- 11970417
TI  - Unstable dimension variability in coupled chaotic systems.
AB  - Systems of coupled chaotic maps and flows arise in many situations of physical
      and biological interest. The aim of this paper is to analyze and to present
      numerical evidence for a common type of nonhyperbolic behavior in these systems:
      unstable dimension variability. We show that unstable periodic orbits embedded in
      the dynamical invariant set of such a system can typically have different numbers
      of unstable directions. The consequence of this may be severe: the system cannot
      be modeled deterministically in the sense that no trajectory of the model can be
      realized by the natural chaotic system that the model is supposed to describe and
      quantify. We argue that unstable dimension variability can arise for small values
      of the coupling parameter. Severe modeling difficulties, nonetheless, occur only
      for reasonable coupling when the unstable dimension variability is appreciable.
      We speculate about the possible physical consequences in this case.

PMID- 11970418
TI  - Crossover from chaotic to self-organized critical dynamics in jerky flow of
      single crystals.
AB  - We report a crossover from chaotic to self-organized critical dynamics in the
      Portevin-Le Chatelier effect in single crystals of Cu-10% Al in tension as a
      function of the applied strain rate. For low and intermediate strain rates, we
      provide an unambiguous support for the existence of chaotic stress drops by
      showing the existence of a finite correlation dimension and a stable positive
      Lyapunov exponent. A surrogate data analysis rules out the possibility that the
      time series is due to a power law stochastic process. As the strain rate is
      increased, the distributions of stress drops and the time intervals between the
      stress drops change from peaked to power law type with an exponent close to unity
      reminiscent of self-organized critical state. A scaling relation compatible with
      self-organized criticality relates the various exponents. The absence of a finite
      correlation dimension and a stable positive Lyapunov exponent at the highest
      strain rate also supports the evidence of crossover.

PMID- 11970419
TI  - Improvement of the local prediction of chaotic time series.
AB  - In this paper we explore the effect of pseudofalse neighbor points, which are
      true neighbor points in the reconstructed attractor, but which are considered not
      suitable to be used when local methods are adopted to predict the chaotic time
      series. In our approach, the epsilon(p) neighbor points are used to reduce the
      influence of the pseudofalse neighbor points, thereby improving the performance
      of the local prediction of the chaotic time series.

PMID- 11970420
TI  - Using unstable periodic orbits to overcome distortion in chaotic signals.
AB  - Proposals to use chaos for communications have been hindered by the fact that
      broadband chaotic signals are distorted by narrow band or frequency dependent
      communications channels. I show in this paper how the unstable periodic orbits
      from a chaotic attractor may be used to estimate the parameters of a filter that
      has acted on a signal from that attractor and estimate the chaotic signal, even
      when additive noise larger than the chaotic signal is present.

PMID- 11970421
TI  - Riddling, bubbling, and Hopf bifurcation in coupled map systems.
AB  - In a simple coupled-map system, we show that the desynchronization of the chaotic
      attractor occurs through a series of Hopf bifurcations. As a result of the
      accumulation of these processes, the blowout bifurcation of this coupled map
      system is a new kind of Hopf bifurcation from a chaotic attractor. Riddling,
      bubbling, and characters of this particular manifestation of Hopf bifurcation
      from a chaotic attractor are studied in this paper.

PMID- 11970422
TI  - Passage through resonance and autoresonance in x(2n)-type potentials.
AB  - Resonant dynamics of a particle in an x(2n)-type potential driven by an
      oscillation with adiabatically varying frequency is investigated. It is shown
      that, under certain conditions, when the driving frequency increases in time and
      passes the resonance with the unperturbed system, the oscillator phase locks to
      the drive and, later, this phase locking is sustained, i.e., the system remains
      in autoresonance. The initial phase locking by passage through resonance is the
      main ingredient of the transition to autoresonance and comprises the
      generalization of previous results for nearly parabolic potentials.

PMID- 11970423
TI  - Fluid flow through ramified structures.
AB  - We investigate the fluid flow through two-dimensional ramified structures by
      direct simulation of the Navier-Stokes equations. We show that for trees with n
      generations, the flow distribution strongly depends on the Reynolds number Re.
      Specifically, for a tree without loops the flow becomes highly heterogeneous at
      high Re. For a tree with loops, on the other hand, the flow distribution tends to
      be more uniform at increased Re conditions. We show that these apparently
      contradictory behaviors have the same origin, namely, the effect of inertia on
      the momentum transport in the channels of the ramified geometry. In order to
      simulate the propagation of the flow imbalance throughout the tree without loops,
      we develop a simple model that incorporates the basic fluid dynamics features of
      the system. For large trees, the results of the model indicate that the
      distribution of flow at the outlet branches can be described by a self-affine
      landscape. Finally, we argue that the nonuniform partitioning of flow found for
      the structure without loops may contribute to the morphogenesis and functioning
      of the bronchial tree.

PMID- 11970424
TI  - Monte Carlo approach to the gas-liquid transition in porous materials.
AB  - The gas-liquid transition of a "quenched-annealed"(QA) system is studied by grand
      canonical Monte Carlo simulation. The "quenched" particles are hard spheres
      within configurations chosen randomly from those of an equilibrium hard-sphere
      system at given density. The fluid particles interact with the matrix particles
      by a hard-core potential and with each other by a hard-core potential and an
      additional potential of a Lennard-Jones type. Our results are in good qualitative
      agreement with various theoretical approaches. With increasing matrix density the
      critical temperature is lowered compared to that of the bulk system and the gap
      between the gas and liquid densities narrowed. Our simulations confirm, for this
      QA system, the possibility of two fluid-fluid transitions substituting for the
      unique gas-liquid transition of the bulk system. They demonstrate the necessity
      to average over a significant number of matrix realizations in order to obtain a
      quantitative location of the phase coexistence lines.

PMID- 11970425
TI  - Viscoelastic behavior of water in the terahertz-frequency range: an inelastic x
      ray scattering study.
AB  - High-resolution, inelastic x-ray scattering measurements of the dynamic structure
      factor S(q,omega) of liquid water in the THz frequency range have been performed
      as a function of wave vector q (1-7 nm(-1)) and temperature T (273-473 K), using
      pressure (0-1.5 kbar) to keep the density at rho approximately 1 g/cm(3). We show
      that, for q<or=2 nm(-1), the S(q,omega) spectra can be consistently explained in
      terms of a hydrodynamic formalism which includes a viscoelastic, q-independent
      contribution to the memory function for the density fluctuations. This allows us
      to extract values for the infinite frequency sound velocity and for the
      structural relaxation time which are found to compare favorably with those
      obtained using techniques which probe a lower-frequency range. As a consequence,
      the atomic dynamics in water is shown to have a homogeneous character down to a
      length scale of approximately 3 nm. At q>2 nm(-1), we find that the viscoelastic
      contribution to the memory function becomes q dependent. Thus this work provides
      a view on the evolution of the collective dynamics of water across the q region
      where the continuum approximation inherent in the hydrodynamic formulation begins
      to fail. The physical consequences of such a result are discussed in some detail.

PMID- 11970426
TI  - Towards a computational chemical potential for nonequilibrium steady-state
      systems.
AB  - We explore an approach to derive a computable chemical potential analog for
      thermostatted steady-state systems arbitrarily far from equilibrium. Although our
      method is not rigorous, it is based on theoretical and numerical evidence and
      exploits analogies with Widom's method widely used in computer simulations of
      equilibrium fluids. We obtain two formulas, one for steady states and one for the
      transient region. Despite being analogous to the equilibrium expression, the
      steady-state formula can only be used for approximate calculations. Possessing
      less obvious characteristics, we present representative calculations for the
      transient approach and discuss its numerical feasibility.

PMID- 11970427
TI  - Two-particle dispersion by correlated random velocity fields.
AB  - We consider the two-particle dispersion in a velocity field, where the relative
      two-point velocity scales according to v(2)(r) proportional, variantr(alpha) and
      the corresponding correlation time scales as tau(r) proportional r(beta). We show
      that for alpha/2+beta<1 the diffusion approximation holds, and the increase in
      the interparticle distances is governed by the distance-dependent diffusion
      coefficient K(r) proportional r(alpha+beta). The possible regimes outside of the
      validity of diffusion approximation are discussed. The Kolmogorov scaling in
      turbulent flow alpha=beta=2/3 corresponds to a borderline situation. The
      experimental data for this case suggest that the separation regime is probably
      ballistic.

PMID- 11970429
TI  - Two-dimensional turbulence in the inverse cascade range.
AB  - Numerical and physical experiments on forced two-dimensional Navier-Stokes
      equations show that transverse velocity differences are described by "normal"
      Kolmogorov scaling <(deltav)(2n)> proportional r(2n/3) and obey Gaussian
      statistics. Since nontrivial scaling is a sign of the strong nonlinearity of the
      problem, these two results seem to contradict each other. A theory explaining
      these observations is presented in this paper. The derived self-consistent
      expression for the pressure gradient contributions leads to the conclusion that
      small-scale transverse velocity differences are governed by a linear Langevin
      like equation, stirred by a nonlocal, universal, solution-dependent Gaussian
      random force. This explains the experimentally observed Gaussian statistics of
      transverse velocity differences and their Kolmogorov scaling. The solution for
      the PDF of longitudinal velocity differences is based on the numerical smallness
      of the energy flux in two-dimensional turbulence. The theory makes a few
      quantitative predictions that can be tested experimentally.

PMID- 11970428
TI  - Thermodynamically self-consistent theories of fluids interacting through short
      range forces.
AB  - The self-consistent Ornstein-Zernike approximation (SCOZA), the generalized mean
      spherical approximation (GMSA), the modified hypernetted chain (MHNC)
      approximation, and the hierarchical reference theory (HRT) are applied to the
      determination of thermodynamic and structural properties, and the phase diagram
      of the hard-core Yukawa fluid (HCYF). We investigate different Yukawa-tail
      screening lengths lambda, ranging from lambda=1.8 (a value appropriate to
      approximate the shape of the Lennard-Jones potential) to lambda=9 (suitable for a
      simple one-body modelization of complex fluids like colloidal suspensions and
      globular protein solutions). The comparison of the results obtained with computer
      simulation data shows that at relatively low lambda's all the theories are fairly
      accurate in the prediction of thermodynamic and structural properties; as far as
      the phase diagram is concerned, the SCOZA and HRT are able to predict the binodal
      line and the critical parameters in a quantitative manner. At lambda=4 some
      discrepancies begin to emerge in the performances of the different theoretical
      approaches: the MHNC remains, on the whole, reasonably accurate in predicting the
      energy and the contact value of the radial distribution function; the SCOZA
      predicts well the equation of state up to the highest lambda values investigated.
      The GMSA and the MHNC underestimate and overestimate, respectively, the liquid
      coexisting density, while the SCOZA and HRT yield liquid branches that fall
      between the two former theoretical predictions, although both appear to
      overestimate the critical temperature somewhat. At higher lambda's the GMSA and
      MHNC binodals further worsen, while the SCOZA appears to remain usefully
      predictive. In general, the predictions of all the theories tend to slightly
      worsen at low temperatures and high density. The determination of the freezing
      line, performed by means of a one-phase "freezing criterion" (due to other
      authors) is not particularly satisfactory within either the SCOZA or the MHNC;
      the GMSA prediction for the freezing line at lambda=7 and 9 is instead able to
      follow in a qualitative manner the pattern of the solid-vapor coexistence line as
      determined through computer simulation studies. The necessity of further
      assessments of the freezing predictions is also discussed. Finally, versions of
      the GMSA, SCOZA, and HRT that can be expected to be more accurate for
      interactions with extremely short-ranged attractions are identified.

PMID- 11970430
TI  - Phase loops in density-functional-theory calculations of adsorption in nanoscale
      pores.
AB  - Phase loops with multiple solutions are observed in calculations of lattice
      density-functional theory. It is shown that the standard numerical methods for
      solving such problems distort the solution. A technique is proposed to obtain
      multiple solutions for phase equilibria in confined fluids. This method gives the
      entire phase equilibrium curve, including hidden points which determine wetting
      transitions and capillary condensation. A synergetic effect of walls on
      adsorption in nanoscale pores is analyzed.

PMID- 11970431
TI  - Nonequilibrium-molecular-dynamics investigation of the presmectic behavior of the
      viscosities of a Gay-Berne nematic liquid crystal.
AB  - Using the method of nonequilibrium molecular dynamics, the behavior of the
      Miesowicz, Helfrich, and Leslie viscosities as functions of temperature and
      density are investigated. In particular, attention is focused on the region
      immediately preceding the nematic-smectic phase transition. The Miesowicz
      viscosity eta1 for the orientation parallel to the direction of flow and the
      Helfrich viscosity eta12 are both found to increase rapidly as the phase
      transition is approached. In most of the cases investigated, a critical exponent
      nu=1 / 3 is found. Values closer to nu=1 / 4 are also found, but in these cases,
      the errors are sufficiently large for nu=1 / 3 to be possible. No nonregular
      behavior of the viscosity coefficients eta2, eta3, gamma1, and gamma2 in the
      presmectic region was detected.

PMID- 11970432
TI  - Dynamics of solitary waves in smectic-C* liquid crystals.
AB  - The dynamics of solitary waves in ferroelectric liquid crystals is considered in
      the context of an overdamped double sine-Gordon model. Various possible types of
      single waves are studied. The dependence of wave velocity and scale on the system
      parameters and initial conditions is found. Sharp initial profiles lead to waves
      with a universal form. The parameters of the wave arising from smooth profiles
      are determined also by the scale of the initial conditions. Numerical
      calculations show good agreement with analytical results. The possibility of
      using such waves to improve the characteristics of liquid crystal devices is also
      discussed.

PMID- 11970434
TI  - Non-Debye screening of a surface charge and a bulk-ion-controlled anchoring
      transition in a nematic liquid crystal.
AB  - We study the anchoring mechanism due to substrate-adsorbed ions by examining a
      related anchoring transition. An analytical solution to the Poisson equation
      shows that, as their number suffices for a non-negligible anchoring contribution,
      the surface field is screened over some characteristic microscopic distance. It
      is shown both theoretically and experimentally that the critical temperature of
      the transition can be controlled by bulk ion density through its relation to the
      density of adsorbed ions.

PMID- 11970433
TI  - Electric-field-induced chiral separation in liquid crystals.
AB  - Recently it was shown that smectic liquid crystal phases formed by achiral banana
      shaped molecules are chiral. Films of such phases generally contain both
      homochiral (consisting of layers of the same chirality) and racemic (the
      chirality alternates in subsequent layers) domains. So far it has not been clear
      how to control the overall chirality of the sample. By observing the effects of
      the application of suitable electric fields, it was noted that chirality of a
      film of banana shaped molecules was interchanged between homochiral and racemic.
      We present dielectric, electro-optic, and polarization current measurements on
      both the racemic and chiral states. The observations indicate that the synclinic
      states have minimum free energies. The observed dielectric modes can be explained
      by a simple model assuming that the antiferroelectric state is very weak.

PMID- 11970435
TI  - Monte Carlo simulation of smectic liquid crystals and the electroclinic effect:
      the role of molecular shape.
AB  - Using Monte Carlo simulation methods, we explore the role of molecular shape in
      the phase behavior of liquid crystals and the electroclinic effect. We study a
      "bent-rod" mesogen shaped like the letter Z, composed of seven soft spheres
      bonded rigidly together with no intramolecular degrees of freedom. For strongly
      angled molecules, we find that steric repulsion alone provides the driving force
      for a smectic-C phase, even without intermolecular dipole-dipole interactions.
      For weakly angled (nearly rodlike) molecules, we find a stable smectic-A (SmA)
      phase and a strong electroclinic effect with a saturation tilt angle of about 19
      degrees. In the SmA phase we find evidence of vortexlike point defects. We also
      observe a field-induced nematic-smectic phase transition.

PMID- 11970436
TI  - Frequency-induced structure transition of nematic electroconvection in twist
      cells.
AB  - We investigate electroconvection of nematic liquid crystals in planar 90 degrees
      twist cells in the dielectric regime. These cells provide competing boundary
      conditions for the nematic director at both electrodes. When the ratio of cell
      gap and roll width is not too small (in thin cells and at low frequencies), the
      convection rolls form along the director in the cell middle, which is diagonal to
      the anchoring directions. This is in accordance with known behavior in the
      conduction regime and with the assumption of a bulk instability (rolls traversing
      the cell). When the ratio of roll periodicity to cell gap is very small in the
      high-frequency range and the thick cells, a regular convection pattern sets in
      with wave vectors directed along the two alignment directions. We suggest the
      interpretation that two independent systems of convection rolls form localized
      near the electrode plates. It is very likely that a similar behavior occurs in
      nontwisted cells where it is difficult to identify experimentally.

PMID- 11970437
TI  - Electro-optic response of surface-induced nematic order above the nematic
      isotropic phase transition temperature.
AB  - The optical retardation of a liquid crystal above the nematic-isotropic phase
      transition temperature T(NI) and subjected to planar alignment conditions at the
      substrate was investigated in the presence of an electric field applied normal to
      the substrates. The response was found to exhibit "S"-shaped behavior with
      electric field, and was larger near T(NI) than well above T(NI). The results were
      examined in the context of a model that permits both biaxiality and a field
      induced tilt of the molecular director. The results suggest that the primary
      effect of the electric field is to induce biaxiality, and in consequence suppress
      the order induced by the surface. No clear indication of a Freedericksz-like
      transition, either experimental or theoretical, was observed.

PMID- 11970438
TI  - Effects of quenched disorder on the orientational order of the octylcyanobiphenyl
      liquid crystal.
AB  - Deuteron NMR (DNMR) measurements were performed with high-temperature and
      spectral resolution on the octylcyanobiphenyl (8CB) liquid crystal confined to
      the randomly interconnected pores of silica aerogel as a function of temperature
      and silica density. The aerogel density was varied by one order of magnitude and
      the temperature spanned the isotropic (I), nematic (N), and smectic-A (SmA)
      phases of 8CB. For all samples, the liquid crystal was confined to pores smaller
      than the micron-sized magnetic coherence length. Thus the observed line shapes
      reflect the director pattern, n(r-->), and the orientational order, Q, as
      dictated by the porous host. The DNMR spectral patterns are consistent with
      powder line shapes representative of a randomized n(r-->) characterized by a
      single Q. The nematic domains formed are of finite dimension that likely exceeds
      the confining size. The weakly first-order nematic-to-isotropic phase transition
      becomes less discontinuous with decreasing pore size, eventually becoming
      continuous at an aerogel density between 0.36 and 0.5 g/cm(3). In the most severe
      confinement, no phase transitions are observed with only a continuous evolution
      of Q present. The orientational order is suppressed from the bulk's with no
      enhancement upon the onset of the SmA phase. This indicates a decoupling of
      nematic and smectic order parameters and a severe suppression of the SmA phase by
      this porous media.

PMID- 11970439
TI  - Theoretical model for layer rotations in smectic-A* liquid crystals subject to
      asymmetric electric fields.
AB  - Recently, observations of the rotation of smectic layers under certain
      experimental conditions have been reported in the literature. In this work, the
      mechanism of such rotations in chiral smectic-A* liquid crystals under the action
      of asymmetric, periodic electric fields is studied theoretically. The general
      conditions for layer rotations have been established using symmetry arguments,
      and a generalized dynamical theory of the chiral smectic-A* phase, coupling layer
      rotations and the electroclinic effect, has been developed. The theory is applied
      in the specific case when an asymmetric sawtooth electric field is applied over
      the system, and the dependence of the average angular velocity of the smectic
      layers on the relevant material constants of the liquid crystal and experimental
      control parameters is calculated. By rewriting the final equations into
      dimensionless form, it is demonstrated that the system exhibits a universal
      behavior, reducing the number of independent material constants and control
      parameters considerably.

PMID- 11970440
TI  - Deuteron NMR study of a long-chain smectic liquid crystal: molecular order and
      dynamics.
AB  - Deuteron Zeeman (T(1Z)) and quadrupolar (T(1Q)) spin-lattice relaxation times and
      quadrupolar splittings were measured in the nematic and smectic A phases of a
      chain-deuterated 4-n-octyloxy-4'-cyanobiphenyl (8OCB-d17) at 15.1 and 46 MHz. To
      model the NMR observables, the so-called pentane effect is used to limit the
      number of possible conformations in the chain, and is found to be a good
      approximation. The additive potential method is employed to construct the
      potential of mean torque using the quadrupolar splittings. A decoupled model is
      used to describe correlated internal motions in the chain, which are independent
      of the molecular reorientation. The latter motion is treated using the small-step
      rotational diffusion model of Nordio (Tarroni and Zannoni), while the former
      motion is described using a master rate equation. In the nematic phase, order
      director fluctuations are found to be necessary. The relaxation data in both
      mesophases were treated using a global target method, and the derived motional
      parameters are acceptable in comparison with those found for 6OCB.

PMID- 11970441
TI  - Nematic kink states in a laser field.
AB  - We have investigated the nonlinear optical interaction of uniform and kink states
      of a nematic and a ferrofluid-doped nematic (ferronematic) liquid crystal with an
      incident laser field. We find that the transition between the permitted uniform
      oreintational states of these systems is of first order in the case of nematics,
      and of second order in the case of ferronematics. In the latter case we also find
      the phenomenon of reentrance. We find new kink states in a magnetic field with
      topological winding different from pi in the case of nematics, and 2pi in the
      case of ferronematics. In ferronematics, due to grain segregation the phase
      diagrams for uniform and kink states are entirely different. In these systems we
      find a first or second order structural transformation from a single kink into a
      pair of kinks. Further, we obtain a rich variety of kink states as the intensity
      of the laser field is varied.

PMID- 11970442
TI  - Critical states in a dissipative sandpile model.
AB  - A directed dissipative sandpile model is studied in two dimensions. Numerical
      results indicate that the long time steady states of this model are critical when
      grains are dropped only at the top, or everywhere. The critical behavior is mean
      field-like. We discuss the role of infinite avalanches of dissipative models in
      periodic systems in determining the critical behavior of same models in open
      systems.

PMID- 11970443
TI  - Topological aspects of geometrical signatures of phase transitions.
AB  - Certain geometric properties of submanifolds of configuration space are
      numerically investigated for classical phi(4) models in one and two dimensions.
      Peculiar behaviors of the computed geometric quantities are found only in the two
      dimensional case, when a phase transition is present. The observed phenomenology
      strongly supports, though in an indirect way, a recently proposed topological
      conjecture about a topology change of the configuration space submanifolds as
      counterpart to a phase transition.

PMID- 11970444
TI  - Two-finger selection theory in the Saffman-Taylor problem.
AB  - We find that solvability theory selects a set of stationary solutions of the
      Saffman-Taylor problem with coexistence of two unequal fingers advancing with the
      same velocity but with different relative widths lambda1 and lambda2 and
      different tip positions. For vanishingly small dimensionless surface tension d0,
      an infinite discrete set of values of the total filling fraction
      lambda=lambda1+lambda2 and of the relative individual finger width
      p=lambda1/lambda are selected out of a two-parameter continuous degeneracy. They
      scale as lambda-1/2 approximately d0(2/3) and p-1/2 approximately d0(1/3). The
      selected values of lambda differ from those of the single finger case. Explicit
      approximate expressions for both spectra are given.

PMID- 11970445
TI  - Jarzynski equality for the transitions between nonequilibrium steady states.
AB  - Jarzynski equality [Phys. Rev. E 56, 5018 (1997)], which has been considered to
      be valid for the transitions between equilibrium states, is found to be
      applicable to the transitions between nonequilibrium stationary states satisfying
      certain conditions. Also numerical results confirm its validity. Its relevance
      for nonequilibrium thermodynamics of the operational formalism is discussed.

PMID- 11970446
TI  - Phase ordering in chaotic map lattices with conserved dynamics.
AB  - Dynamical scaling in a two-dimensional lattice model of chaotic maps, in contact
      with a thermal bath at temperature T, is numerically studied. The model here
      proposed is equivalent to a conserved Ising model with couplings that fluctuate
      over the same time scale as spin moves. When coupling fluctuations and thermal
      fluctuations are both important, this model does not belong to the class of
      universality of a Langevin equation known as model B; the scaling exponents are
      continuously varying with T and depend on the map used. The universal behavior of
      model B is recovered when thermal fluctuations are dominant.

PMID- 11970447
TI  - Convection-driven quadrupolar dynamos in rotating spherical shells.
AB  - It is found that for Taylor numbers of the order 10(8) quadrupolar dynamos
      aligned with the axis of rotation are preferred in comparison with dipolar
      dynamos. This preference holds for a range of Prandtl numbers P and magnetic
      Prandtl numbers P(m) in the neighborhood of unity. The main time-dependent
      feature of the quadrupolar dynamos are polward traveling waves.

PMID- 11970448
TI  - Traveling-wave relaxation in elongated liquid crystal cells.
AB  - We have made a theoretical study of Freedericksz relaxation in a long thin
      nematic liquid crystal cell subject to strong anchoring on the short ends and
      weak anchoring on the long sides. On removing an imposed magnetic field, three
      different types of relaxation behavior may be observed. Two of these are simple
      generalizations of one-dimensional relaxation channels, and are dominated by
      either the ends or the sides. The third is a traveling wave, nucleated by the
      strong anchoring ends of the cell but driven by the weak anchoring sides and is
      the result of a subtle balance between the two classical mechanisms. A phase
      diagram is derived, identifying the relaxation regimes as a function of the
      nondimensional initial field and the anchoring strength in the long cell limit. A
      comparison is made between numerical results and a simple one-dimensional theory
      derived from an asymptotic analysis. Surprisingly, the traveling wave behavior
      occurs for a large region of parameter space.

PMID- 11970449
TI  - Layer-by-layer crystallization and the role of fluctuations in free standing
      smectic films.
AB  - Specular x-ray reflectivity has been used to study the changes in the thermal
      fluctuation behavior of eight layer freely suspended N-(4-n-butoxybenzilidene)-4
      n-octylaniline (4O.8) films during the process of successive layer-by-layer
      crystallizations. Each of these steps is preceded by the formation of an
      intermediate layer structure with in-plane hexatic ordering. We find an unusually
      large reduction of the fluctuations after the emergence of only the first hexatic
      toplayer. The fluctuation profiles over the film are in all cases quenched at the
      surfaces though less so after each crystallization step. This behavior supports
      theoretical arguments that hexatic order is reduced by out-of-plane smectic layer
      fluctuations.

PMID- 11970450
TI  - Dislocation profile in cholesteric finger texture.
AB  - The displacement field around an isolated elementary dislocation in a medium with
      one-dimensional periodicity is established experimentally. The system studied is
      a cholesteric fingerprint texture with a macroscopic ( approximately 10 microm)
      periodicity. The characteristic elastic length is smaller than the "interlayer"
      distance. As a result, the experimental dislocation profile deviates from the
      classic pattern predicted by the linear elastic theory but fits well with the
      recently suggested nonlinear theory of dislocation [Phys. Rev. E 59, R4752
      (1999)].

PMID- 11970451
TI  - Memories in sand: experimental tests of construction history on stress
      distributions under sandpiles.
AB  - We report experiments on piles of cohesionless granular materials showing the
      effect of construction history on static stress distributions. Stresses under
      piles are monitored by sensitive capacitive techniques. The piles are formed
      either by pouring granular material from a funnel with a small outlet (localized
      source), or from a large sieve (homogeneous rain). Localized sources yield stress
      profiles with a clear stress dip near the center of the pile; the homogeneous
      rain profiles have no stress dip. We show that the stress profiles scale linearly
      with the pile height. Experiments on wedge-shaped piles show similar but weaker
      effects.

PMID- 11970452
TI  - Critical angle of wet sandpiles.
AB  - We measure the increase in the maximum stable angle of a sandpile, theta(c), with
      the volume fraction, phi of a liquid added to cause cohesion between the grains.
      For two different liquids, tan theta(c) does not apparently scale with the air
      liquid surface tension at low phi, whereas it does at higher phi. This suggests
      that the liquid forms menisci at asperities on the surfaces of the grains before
      filling cohesive menisci at intergrain contact points. In this cohesive limit,
      theta(c)(phi) agrees with a surface roughness theory. Electron and fluorescence
      microscopy of the dry and wet surfaces of the grains support this model.

PMID- 11970453
TI  - Field theoretical representation of the Hohenberg-Kohn free energy for fluids.
AB  - To go beyond Gaussian approximation to the Hohenberg-Kohn free energy playing the
      key role in the density functional theory (DFT), the density functional integral
      representation would be relevant, because the field theoretic approach to
      perturbative calculations becomes available. Then we first derive the associated
      Hamiltonian of the density functional, explicitly including the logarithmic
      entropy term, from the grand partition function expressed by configurational
      integrals. Moreover, two things are done so that the efficiency of the obtained
      form may be revealed: we demonstrate that this representation facilitates the
      field theoretic treatment of the perturbative calculation and, further, compare
      our perturbative formulation with that of the DFT.

PMID- 11970454
TI  - Landau damping of an electron plasma wave in a plasma with modulated density.
AB  - The collisionless Landau damping is analyzed for a homogeneous plasma with a
      sinusoidal density perturbation. The exact damping values are obtained by
      numerically solving the kinetic dispersion relation of the electron plasma mode.
      Quantitative results are provided on the influence of the amplitude and the wave
      vector of the density modulation. Within a simplified fluid framework, a fit is
      given to these data.

PMID- 11970455
TI  - Two-color multistep cascading and parametric soliton-induced waveguides.
AB  - We introduce the concept of two-color multistep cascading for vectorial
      parametric wave mixing in optical media with quadratic (second-order or chi(2))
      nonlinear response. We demonstrate that the multistep cascading allows light
      guiding-light effects with quadratic spatial solitons. With the help of the so
      called "almost exact" analytical solutions, we describe the properties of
      parametric waveguides created by two-wave quadratic solitons.

PMID- 11970456
TI  - Ultraresolution in optical imaging using spatiotemporal scanning.
AB  - Spatial information exceeding the passband of an imaging system can be captured
      by using the optics to generate a spatiotemporal multiple beam interference
      pattern that is scanned over the object, rather than using it to image the object
      directly. The modulation of the higher temporal harmonics of the signal resulting
      from collecting the scattered light represents a mapping in the time domain of
      higher spatial harmonics of the data. Upon reconstruction, the additional
      temporal degrees of freedom are mapped back in the spatial domain where they
      represent spatial frequencies exceeding the passband of the optics. The spatial
      resolution is thus not limited by the spatial passband, but rather by the
      temporal bandwidth of the detection system. Due to hardware limitations,
      experimental demonstration is provided only for a one-dimensional scan of Ronchi
      gratings with 50 and 200 lines per inch.

PMID- 11970457
TI  - Engineered nonlinear lattices.
AB  - We show that with the quasi-phase-matching technique it is possible to fabricate
      stripes of nonlinearity that trap and guide light like waveguides. We investigate
      an array of such stripes and find that when the stripes are sufficiently narrow,
      the beam dynamics is governed by a quadratic nonlinear discrete equation. The
      proposed structure therefore provides an experimental setting for exploring
      discrete effects in a controlled manner. In particular, we show propagation of
      breathers that are eventually trapped by discreteness. When the stripes are wide
      the beams evolve in a structure we term a quasilattice, which interpolates
      between a lattice system and a continuous system.

PMID- 11970458
TI  - Drying of capillary porous media with a stabilized front in two dimensions.
AB  - We study a two-dimensional model of drying of capillary porous media when gravity
      or viscous forces lead to the formation of a stabilized front. When gravity
      forces stabilize the front, the mean front width, defined as the mean
      perpendicular distance between the front's most advanced and least advanced
      points, is found theoretically to scale with the Bond number B as B(
      1+(1+beta)/(1+nu)), where beta is the percolation probability exponent and nu is
      the correlation length exponent. This scaling is confirmed numerically and is
      consistent with the experimental results of Shaw [Phys. Rev. Lett. 59, 1671
      (1987)]. The global mass transfer coefficient of the front is studied
      numerically. To this end, we study the position z(c)-delta of the equivalent
      smooth line leading to the same evaporation flux as the front. In the transient
      case, z(c)-delta is found to scale with the Bond number B as B-0.63. In the
      stationary case, i.e., when the front reaches a stationary position within the
      medium, it is found that z(c)-delta approximately sigma where sigma is the
      standard deviation of the positions of the points forming the front around its
      mean position z(c). These results are exploited to study the evaporation flux
      when viscous effects stabilize the front. In particular, we discuss the
      possibility of nontrivial behaviors, i.e., drying rates not scaling as 1/square
      root of t for drying under constant external conditions.

PMID- 11970459
TI  - Viscoelasticity of randomly branched polymers in the vulcanization class.
AB  - We report viscosity, recoverable compliance, and molar mass distribution for a
      series of randomly branched polyester samples with long linear chain sections
      between branch points. Molecular structure characterization determines tau=2.47+/
      0.05 for the exponent controlling the molar mass distribution, so this system
      belongs to the vulcanization (mean-field) universality class. Consequently,
      branched polymers of similar size strongly overlap and form interchain
      entanglements. The viscosity diverges at the gel point with an exponent s=6.1+/
      0.3, that is significantly larger than the value of 1.33 predicted by the
      branched polymer Rouse model (bead-spring model without entanglements). The
      recoverable compliance diverges at the percolation threshold with an exponent
      t=3.2+/-0.2. This effect is consistent with the idea that each branched polymer
      of size equal to the correlation length stores k(B)T of elastic energy. Near the
      gel point, the complex shear modulus is a power law in frequency with an exponent
      u=0.33+/-0.05. The measured rheological exponents confirm that the dynamic
      scaling law u=t/(s+t) holds for the vulcanization class. Since s is larger and u
      is smaller than the Rouse values observed in systems that belong to the critical
      percolation universality class, we conclude that entanglements profoundly
      increase the longest relaxation time. Examination of the literature data reveals
      clear trends for the exponents s and u as functions of the chain length between
      branch points. These dependencies, qualitatively explained by hierarchical
      relaxation models, imply that the dynamic scaling observed in systems that belong
      to the vulcanization class is nonuniversal.

PMID- 11970460
TI  - Multiple scattering suppression in static light scattering by cross-correlation
      spectroscopy.
AB  - Cross-correlation techniques have been used successfully to suppress multiple
      scattering in dynamic light-scattering experiments on turbid samples. This allows
      dynamic information to be obtained straightforwardly by processing the remaining
      single scattering. Here we show that cross-correlation techniques can also be
      used to suppress multiple scattering in static light-scattering measurements. We
      use the two-color dynamic light-scattering method and exploit the fact that the
      amplitude of the time-dependent part of the measured intensity cross-correlation
      function depends on the ratio of the single-scattered intensity to the total
      (single + multiple) scattered intensity. The method is illustrated by
      measurements of the static structure factors of concentrated suspensions of "hard
      sphere" colloids. Good agreement is found with those calculated in the Percus
      Yevick approximation.

PMID- 11970461
TI  - Self-consistent expansion for the Kardar-Parisi-Zhang equation with correlated
      noise.
AB  - A minor modification of the self-consistent expansion (SCE) for the Kardar-Parisi
      Zhang (KPZ) system with uncorrelated noise is used to obtain the exponents in
      systems where the noise has spatial long-range correlations. For d-dimensional
      systems with correlations of the form D((-->)r-(-->)r',t-t')=2D(0)/(-->)r-(-
      >)r'/2 rho-d)delta(t-t'), (rho>0), we find a lower critical dimension
      d(0)(rho)=2+2 rho, above which a perturbative Edwards-Wilkinson (EW) solution
      appears. Below the lower critical dimension two solutions exist, each in a
      different, distinct region of rho. For small rho's the solution of KPZ with
      uncorrelated noise is recovered. For large rho's a rho-dependent solution is
      found. The existence of only one solution in each region of rho is not a result
      of a competition between two solutions but a direct outcome of the SCE equation.

PMID- 11970462
TI  - Quantitative measurements of Ostwald ripening using time-resolved small-angle
      neutron scattering.
AB  - Using a unique method we present accurate quantitative measurements of the
      Ostwald ripening of an emulsion system. Time-resolved small-angle neutron
      scattering monitors the time evolution of the average radius and number density
      of the emulsion drops. The results qualitatively agree with the current theory of
      Ostwald ripening but there is a quantitative, experimentally significant,
      discrepancy of a factor of 1.7. We argue that these accurate experiments,
      performed on a well characterized system, provide a most useful basis for testing
      further refinements of the theory.

PMID- 11970463
TI  - Simple model with facilitated dynamics for granular compaction.
AB  - A simple lattice model is used to study compaction in granular media. As in real
      experiments, we consider a series of taps separated by large enough waiting
      times. The relaxation of the density exhibits the characteristic inverse
      logarithmic law. Moreover, we have been able to identify analytically the
      relevant time scale, leading to a relaxation law independent of the specific
      values of the parameters. Also, an expression for the asymptotic density reached
      in the compaction process has been derived. The theoretical predictions agree
      fairly well with the results from the Monte Carlo simulation.

PMID- 11970464
TI  - Molecular dynamics of a liquid drop spreading in a corner formed by two planar
      substrates.
AB  - Molecular-dynamics simulations were used to investigate the spreading of
      nonvolatile liquid drops in a solid corner formed by two planar substrates. To
      understand the effect of the corner on the spreading, liquid drops in a corner
      with angles of 45 degrees, 90 degrees, and 135 degrees as well as on a flat
      substrate were examined. Both the solid substrate and the liquid drop were
      modeled using the Lennard-Jones interaction potential in the present study.
      Simulation results show that the mass center of the liquid molecules migrated
      towards the corner as time evolved and the spreading rate increased as the corner
      angle decreased. It is found that the variation of the mean spreading area with
      time can be described by a general relation of A(t) approximately t, which is in
      agreement with results obtained by other investigators. The distribution of
      liquid atoms per unit normalized corner degree shows a similar trend for
      different corner angles.

PMID- 11970465
TI  - Directed rigidity and bootstrap percolation in 1+1 dimensions.
AB  - We study directed rigidity percolation (equivalent to directed bootstrap
      percolation) on three different lattices: square, triangular, and augmented
      triangular. The first two of these display a first-order transition at p=1, while
      the augmented triangular lattice shows a continuous transition at a nontrivial
      p(c). On the augmented triangular lattice we find, by extensive numerical
      simulation, that the the directed rigidity percolation transition belongs to the
      same universality class as the directed percolation. The same conclusion is
      reached by studying its surface critical behavior, i.e., the spreading of
      rigidity from finite clusters close to a nonrigid wall. Near the discontinuous
      transition at p=1 on the triangular lattice, we are able to calculate the finite
      size behavior of the density of rigid sites analytically. Our results are
      confirmed by numerical simulation.

PMID- 11970466
TI  - Homogeneous cooling state for a granular mixture.
AB  - The homogeneous cooling state for a binary mixture of inelastic hard spheres is
      studied using the Enskog kinetic theory. In the same way as for the one-component
      fluid, we propose a scaling solution in which the time dependence of the
      distribution functions occurs entirely through the temperature of the mixture. A
      surprising result is that the (partial) temperatures of each species are
      different, although their cooling rates are the same. Approximate forms for the
      distribution functions are constructed to leading order in a Sonine polynomial
      expansion showing a small deviation from Maxwellian, similar to that for the one
      component case. The temperatures and overall cooling rate are calculated in terms
      of the restitution coefficients, the reduced density, and the ratios of mass,
      concentration, and sizes.

PMID- 11970467
TI  - Dynamic entropy as a measure of caging and persistent particle motion in
      supercooled liquids.
AB  - The length-scale dependence of the dynamic entropy is studied in a molecular
      dynamics simulation of a binary Lennard-Jones liquid above the mode-coupling
      critical temperature T(c). A number of methods exist for estimating the entropy
      of dynamical systems, and we utilize an approximation based on calculating the
      mean first-passage time (MFPT) for particle displacement because of its
      tractability and its accessibility in real and simulation measurements. The MFPT
      dynamic entropy S(epsilon) is defined as equal to the inverse of the average
      first-passage time for a particle to exit a sphere of radius epsilon. This
      measure of the degree of chaotic motion allows us to identify characteristic time
      and space scales and to quantify the increasingly correlated particle motion and
      intermittency occurring in supercooled liquids. In particular, we identify a
      "cage" size defining the scale at which the particles are transiently localized,
      and we observe persistent particle motion at intermediate length scales beyond
      the scale where caging occurs. Furthermore, we find that the dynamic entropy at
      the scale of one interparticle spacing extrapolates to zero as the mode-coupling
      temperature T(c) is approached.

PMID- 11970468
TI  - Experimental observations of non-Gaussian behavior and stringlike cooperative
      dynamics in concentrated quasi-two-dimensional colloidal liquids.
AB  - We report, from direct observation of particle trajectories as a function of
      time, the presence of stringlike cooperative motion in a quasi-two-dimensional
      liquid. We have used digital video microscopy to study the equilibrium dynamics
      of suspensions of sterically stabilized uncharged poly(methylmethacrylate)
      spheres confined in a thin glass cell. Our experiments reveal the existence, in
      semidilute and dense liquid states, of a transition in the qualitative dynamical
      behavior of the system. At short times particles undergo unhindered Brownian
      motion, at intermediate times they undergo uncorrelated binary collisions, and at
      long times these one-particle self-diffusive modes are coupled to collective
      longitudinal acoustic modes of the fluid, the signature of which is local
      fluctuating domains of enhanced particle mobility. We study the properties of
      these domains by examining the density dependence of the van Hove self
      correlation function and its deviation from Gaussian behavior. We observe that
      periods of non-Gaussian behavior correlate precisely with the timing of events
      involved in the relaxation of "caged" particles and their nearest neighbors. In
      contrast with relaxation processes in supercooled liquids, the lifetime of
      dynamical heterogeneities in a dissipative colloidal suspension is found to shift
      towards shorter time scales with increasing particle density. During time periods
      for which a quasi-two-dimensional system follows Gaussian behavior, we observe
      that, as predicted by Cichocki and Felderhof [J. Phys. Condens. Matter 6, 7287
      (1994)], the time dependence of the evolution of the effective diffusion
      coefficient from its short time to its long time value has the form (ln t)/t.
      This last finding is true for all observed particle densities. To our knowledge,
      these results are the first experimental verification of the existence of
      microscopic cooperativity and the predicted temporal evolution of the diffusion
      coefficient for Brownian motion in concentrated quasi-two-dimensional liquids.

PMID- 11970469
TI  - Minimal relaxation law for compaction of tapped granular matter.
AB  - Granular systems can compact under the influence of sufficiently strong,
      successive tapping. Recent experimental investigations show that the packing
      fraction obeys a very slow relaxation to a final, dense packing fraction that is
      basically proportional to the inverse of the logarithm of the tap number or time.
      We provide a simple macromechanical argument that explains this inverse
      logarithmic relaxation in time in all functional details. By considering the
      asymptotic limits of the resulting relaxation law, we show that the relaxational
      dynamics of the compaction process can be interpreted as a combination of a
      biased void diffusion for short times and a collective reorganization for large
      times.

PMID- 11970470
TI  - Aspects of the dynamics of colloidal suspensions: further results of the mode
      coupling theory of structural relaxation.
AB  - Results of the idealized mode-coupling theory for the structural relaxation in
      suspensions of hard-sphere colloidal particles are presented and discussed with
      regard to recent light scattering experiments. The structural relaxation becomes
      nondiffusive for long times, contrary to the expectation based on the de Gennes
      narrowing concept. A semiquantitative connection of the wave vector dependences
      of the relaxation times and amplitudes of the final alpha relaxation explains the
      approximate scaling observed by Segre and Pusey [Phys. Rev. Lett. 77, 771
      (1996)]. Asymptotic expansions lead to a qualitative understanding of density
      dependences in generalized Stokes-Einstein relations. This relation is also
      generalized to nonzero frequencies thereby yielding support for a reasoning by
      Mason and Weitz [Phys. Rev. Lett. 74, 1250 (1995)]. The dynamics transient to the
      structural relaxation is discussed with models incorporating short-time diffusion
      and hydrodynamic interactions for short times.

PMID- 11970471
TI  - Computer simulation of microphase separation in ionic copolymers.
AB  - The formation of lamella microphases in symmetric neutral-ionic block copolymers
      has been investigated by constant volume-constant temperature (NVT) molecular
      dynamics computer simulations using a generic coarse-grain model. Computations of
      counterion diffusion, pressure tensor, and the anisotropy of the structure factor
      are used to characterize the order-disorder transition (ODT). There is strong
      counterion condensation on the ionic blocks at temperatures well above the ODT;
      this creates a slight imbalance in the volume composition of the two blocks and
      results in a perforated lamella structure in the microphase. Below the ODT
      counterion diffusion is decoupled from the chain motions but is strongly
      anisotropic due to the microphase morphology. The high counterion diffusional
      mobility is discussed in terms of the relatively low value of the glass
      transition for the ionic blocks.

PMID- 11970472
TI  - Effects of bead-bead interactions on the static and dynamical properties of model
      polymer solutions.
AB  - The effects of segment-segment interactions on the static and dynamical
      properties of model polymer solutions are examined by Brownian dynamics
      simulations in the free-draining limit over a wide concentration range. A bead
      and-spring model is used to describe the polymer chains at a coarse-grained
      level, in which segment-segment interactions are represented by a bead-bead pair
      potential with a Gaussian analytic form, beta u(ev)(r)=A exp(-r(2)/2 sigma(2)),
      where beta=1/k(B)T and A and sigma are characteristic energy and distance scales,
      respectively. The chain dimensions, self-diffusion coefficient, and viscosity of
      the systems are studied as functions of number density of beads of the system,
      rho, at given excluded-volume potential parameters, A and sigma. Our results show
      that in the limit of infinite dilution even for short chains (N approximately 10)
      there is statistically significant scaling behavior in the static and dynamical
      properties. For a system with given values of A and sigma the change in polymer
      coil size shows a realistic trend as the concentration of the system increases.
      In the dilute and concentrated regions the coil size decreases as a result of
      increasing interchain repulsions, while in the highly concentrated region the
      coil size increases again, showing a return to Rouse-like behavior because the
      intrapolymer and interpolymer segment-segment interactions become effectively
      indistinguishable for an arbitrary bead and to a large extent are "balanced out."
      In the limit of infinite dilution, the self-diffusion coefficient of the center
      of mass, D(cm), depends on N only and not on the potential parameter A, while in
      contrast the specific viscosity eta(sp) depends on both N and A. As the
      concentration increases D(cm) decreases and eta(sp) increases consistent with the
      behavior of real polymers. When the system becomes highly concentrated, however,
      both D(cm) and eta(sp) unrealistically return to the Rouse limit. This suggests
      that from the concentrated region upward in concentration, the entanglement or
      the topological constraints caused by the physical connectivity of the chains
      significantly influence their dynamical behavior. The mean-field segment-segment
      interactions or excluded-volume effects incorporated in the current coarse
      grained bead-spring approach cannot capture this entanglement effect, and
      therefore give rise to unrealistic dynamical behavior in the concentrated regime.

PMID- 11970473
TI  - Molecular mode-coupling theory for supercooled liquids: application to water.
AB  - We present mode-coupling equations for the description of the slow dynamics
      observed in supercooled molecular liquids close to the glass transition. The mode
      coupling theory (MCT) originally formulated to study the slow relaxation in
      simple atomic liquids, and then extended to the analysis of liquids composed by
      linear molecules, is here generalized to systems of arbitrarily shaped, rigid
      molecules. We compare the predictions of the theory for the q-vector dependence
      of the molecular nonergodicity parameters, calculated by solving numerically the
      molecular MCT equations in two different approximation schemes, with "exact"
      results calculated from a molecular dynamics simulation of supercooled water. The
      agreement between theory and simulation data supports the view that MCT succeeds
      in describing the dynamics of supercooled molecular liquids, even for network
      forming ones.

PMID- 11970474
TI  - Effects of physisorption of xenon on the thermal conductivity of resorcinol
      formaldehyde aerogels.
AB  - The effects of adsorption of xenon to the thermal conductivity of a resorcinol
      formaldehyde aerogel were investigated in a temperature range from 20 to 120 K.
      It was found that at temperatures below 75 K, the adsorbed xenon has little
      effect on the thermal conductivity. Rapid rises of the thermal conductivity
      develop at temperatures around 75-80 K with magnitudes roughly proportional to
      the amount of xenon adsorbed. The effect is explained as due to adsorbed xenon
      atoms that enhance the neck connection between aerogel particles.

PMID- 11970475
TI  - Generating moment equations in the Doi model of liquid-crystalline polymers.
AB  - We present a self-consistent method for deriving moment equations for kinetic
      models of polymer dynamics. The Doi model [J. Polym. Sci., Polym. Phys. Ed. 19,
      229 (1981)] of liquid-crystalline polymers with the Onsager excluded-volume
      potential is considered as an example. To lowest order, this method amounts to a
      simple effective potential different from the Maier-Saupe form. Analytical
      results are presented which indicate that this effective potential provides a
      better approximation to the Onsager potential than the Maier-Saupe potential.
      Corrections to the effective potential are obtained.

PMID- 11970476
TI  - Microstructure functions for random media with impenetrable particles.
AB  - We introduce a model consisting of nonaligned and impenetrable particles. This
      model is obtained by placing particles of random orientation within "security
      spheres," typically chosen to be spheres in thermal equilibrium. The particles in
      general are allowed to be nonspherical. We obtain an analytical expression for
      the function S(n), the probability that n points simultaneously lie outside of
      the particle phase. This characterization of the microstructure appears in
      certain rigorous bounds on the effective properties of random materials. We also
      evaluate S2 for various specific examples of this model, including nonaligned
      impenetrable ellipsoids.

PMID- 11970477
TI  - Monte Carlo simulations of liquid spreading on a solid surface: effect of end
      group functionality.
AB  - The spreading of liquid droplets composed of molecules with or without reactive
      end groups over a solid surface has been studied using Monte Carlo simulations.
      For molecules without reactive end groups, a molecular layering in the spreading
      profiles is predicted, depending on the ratio of the magnitude of intermolecular
      interactions to thermal energy. As intermolecular interactions become smaller
      than thermal energy, the layered structure vanishes. For molecules with reactive
      end groups, interactions between end groups and between end groups and the
      surface complicate the situation. By assuming an end-to-end interaction between
      molecules and the pinning of end groups to the surface, a complex layered
      structure is obtained. Our simulation predicts spreading profiles that accurately
      describe the broad spectrum of data obtained from scanning microellipsometry for
      perfluoropolyalkylethers with and without reactive end groups.

PMID- 11970478
TI  - Screening of a macroion by multivalent ions: correlation-induced inversion of
      charge.
AB  - Screening of a strongly charged macroion by multivalent counterions is
      considered. It is shown that counterions form a strongly correlated liquid at the
      surface of the macroion. Cohesive energy of this liquid leads to additional
      attraction of counterions to the surface, which is absent in conventional
      solutions of the Poisson-Boltzmann equation. Away from the surface this
      attraction can be taken into account by a new boundary condition for the
      concentration of counterions near the surface. The Poisson-Boltzmann equation is
      solved with this boundary condition for a charged flat surface, a cylinder, and a
      sphere. In all three cases, screening is much stronger than in the conventional
      approach. At some critical exponentially small concentration of multivalent
      counterions in the solution, they totally neutralize the surface charge at small
      distances from the surface. At larger concentrations they invert the sign of the
      net macroion charge. The absolute value of the inverted charge density can be as
      large as 20% of the bare one. In particular, for a cylindrical macroion it is
      shown that for screening by multivalent counterions, predictions of the Onsager
      Manning theory are quantitatively incorrect. The net charge density of the
      cylinder is smaller than their theory predicts and inverts the sign with a
      growing concentration of counterions. Moreover, the condensation loses its
      universality and the net charge linear density depends on the bare one.

PMID- 11970479
TI  - Filler-induced composition waves in phase-separating polymer blends.
AB  - The influence of immobile filler particles (spheres, fibers, platelets) on
      polymer-blend phase separation is investigated computationally using a
      generalization of the Cahn-Hilliard-Cook (CHC) model. Simulation shows that the
      selective affinity of one of the polymers for the filler surface leads to the
      development of concentration waves about the filler particles at an early stage
      of phase separation in near critical composition blends. These "target" patterns
      are overtaken in late-stage phase separation by a growing "background" spinodal
      pattern characteristic of blends without filler particles. The linearized CHC
      model is used to estimate the number of composition oscillations emanating from
      isolated filler particles. In far-off-critical composition blends, an
      "encapsulation layer" grows at the surface of the filler rather than a target
      pattern. The results of these simulations compare favorably with experiments on
      filled phase-separating ultrathin blend films in which the filler particles are
      immobilized on a solid substrate.

PMID- 11970480
TI  - Liquid-induced transitions in granular media.
AB  - We investigate the effect of interstitial liquid on the physical properties of
      granular media by measuring the angle of repose as a function of the liquid
      content. The resultant adhesive forces lead to three distinct regimes in the
      observed behavior as the liquid content is increased: a granular regime in which
      the grains move individually, a correlated regime in which the grains move in
      correlated clusters, and a plastic regime in which the grains flow coherently. We
      discuss these regimes in terms of two proposed theories describing the effects of
      liquid on the physical properties of granular media.

PMID- 11970481
TI  - Diffusivelike buffering and saturation of large rivers.
AB  - We use mass balance data from Asian rivers together with a first-order diffusive
      simplification of the St. Venant-Exner equations to characterize river flood
      plain processes and discuss the reaction of a large model river to a hill slope
      supply of eroded masses. The simple analytical solution derived for the long-term
      profile of the river bed shows that (i) the system converges towards a state in
      which it reacts to perturbations in erosion of the landscape by small-amplitude
      oscillations around an average "stationary" state, (ii) to have an effective
      influence on the river plain profile, the perturbations need to have frequencies
      smaller than the characteristic frequencies of the river system, and (iii) this
      river buffering might be linked with a possible long-term saturation of the
      system carrying capacity.

PMID- 11970482
TI  - Confined water in hydrophobic nanopores: dynamics of freezing into bilayer ice.
AB  - Molecular dynamics simulations for a thin film of water confined to a slit
      nanopore are performed in order to investigate the dynamic process of
      crystallization of the system. The system upon freezing creates a bilayer ice
      crystal composed of two layers of hexagonal rings. We perform one simulation at
      T=257 K during which the system remains a supercooled liquid state, and another
      one at T=253 K during which the system freezes. Many patterns of molecular
      arrangement are found upon freezing, and an account is given of the origin of
      multiple peaks in the distributions of binding energy and pair interaction
      energy. A definition of the solid-like cluster is introduced in order to analyze
      the time evolution of the clusters' population and their shapes. A large variety
      of shapes including highly nonspherical ones can be detected during simulations.
      A steady population of clusters is found at T=257 K, whereas at T=253 K a post
      critical nucleus of the solid phase emerges within a few nanoseconds and
      continues to grow until the system freezes completely.

PMID- 11970483
TI  - Thin diblock copolymer films on patterned surfaces: computer simulations and the
      Frenkel-Kontorowa model.
AB  - We study by direct numerical integration of the dynamical evolution equation the
      equilibrium configuration of a diblock copolymer thin film melt on a patterned
      surface. The surface has a large number of stripes and the mismatch between the
      bulk diblock spacing and the stripe width is small. We investigate primarily the
      formation of small discommensurations in the incommensurate phase and compare the
      results with the predictions of an analogous model of solid-state physics, the
      Frenkel-Kontorowa model.

PMID- 11970484
TI  - Pressure of correlated layer-charge and counterion fluctuations in charged thin
      films.
AB  - We predict the fluctuation contribution to the interaction between two surfaces
      with both mobile layer charges and delocalized counterions. The correlation
      (coupling) between the layer-charge fluctuations and the counterion fluctuations
      (around a piecewise homogeneous mean-field density profile) is taken into account
      in the Gaussian approximation. We find that this correlation significantly
      increases the magnitude of the interlayer fluctuation attraction. The counterion
      fluctuation pressure is calculated as a function of the intersurface distance and
      we show how the large and small distance limits correspond to three-dimensional
      (3D) and 2D fluctuations, respectively. In addition, we predict the charge
      density-density correlation functions. Experimental implications of the model are
      discussed.

PMID- 11970485
TI  - Experimental evidence of power-law trapping-time distributions in porous media.
AB  - We present experimental results of solute transport in porous samples made of
      packings of activated carbon porous grains. Exchange experiments, where the
      tagged solution initially saturating the medium is replaced with the same
      solution without tracer, are accurately described by macroscopic transport
      equations. On the other hand, in desorption experiments, where the tagged
      solution is replaced by water, the solute concentration exhibits a power-law
      decay for long times, which requires a more detailed, mesoscopic description. We
      reproduce this behavior within a continuous-time random-walk approach, where the
      waiting time distribution is related to the desorption isotherm. Results are
      compatible with a power-law trapping time distribution with divergent first
      moment, characteristic of anomalous (sub)diffusion.

PMID- 11970486
TI  - Fluids of hard ellipsoids: Phase diagram including a nematic instability from
      Percus-Yevick theory.
AB  - An important aspect of molecular fluids is the relation between orientation and
      translation parts of the two-particle correlations. Especially, a detailed
      knowledge of the influence of orientation correlations is needed to explain and
      calculate in detail the occurrence of a nematic phase. The simplest model system
      that shows both orientation and translation correlations is a system of hard
      ellipsoids. We investigate an isotropic fluid formed of hard ellipsoids with the
      Percus-Yevick theory. Solving the Percus-Yevick equations self-consistently and
      accurately in the high density regime gives, contrary to previous works, a clear
      criterion for a nematic instability. We calculate in detail the equilibrium phase
      diagram for a fluid of hard ellipsoids of revolution. Our results compare well
      with Monte Carlo simulations and density-functional theory.

PMID- 11970487
TI  - Force measurements on static granular materials.
AB  - A method for measuring normal forces under a granular packing is introduced. A
      high precision electronic balance is used to measure normal forces on individual
      beads at the bottom of a granular material. Due to the high sensitivity of this
      setup the normal forces on individual beads without applying any external load on
      the system were measured. From these measurements the distribution of forces, the
      response to small perturbations at grain level and the spatial correlation
      between normal forces were investigated at the bottom of the packing. The
      distribution function is consistent with a power law with an exponent alpha=0.3
      for small forces. At large forces a crossover to an exponential decay is observed
      with a decay constant beta=1.8. Small amplitude spatial correlations were
      observed in the normal forces at the bottom of the pile, and the radial pressure
      distribution was dependent of the different filling procedures. Finally we report
      on systematic relaxations in the measured weight as a function of time on single
      grains at the bottom of the packing after perturbing the system.

PMID- 11970488
TI  - Extended Eden model reproduces growth of an acellular slime mold.
AB  - A stochastic growth model was used to simulate the growth of the acellular slime
      mold Physarum polycephalum on substrates where the nutrients were confined in
      separate drops. Growth of Physarum on such substrates was previously studied
      experimentally and found to produce a range of different growth patterns [Phys.
      Rev. E 57, 941 (1998)]. The model represented the aging of cluster sites and
      differed from the original Eden model in that the occupation probability of
      perimeter sites depended on the time of occupation of adjacent cluster sites.
      This feature led to a bias in the selection of growth directions. A moderate
      degree of persistence was found to be crucial to reproduce the biological growth
      patterns under various conditions. Persistence in growth combined quick
      propagation in heterogeneous environments with a high probability of locating
      sources of nutrients.

PMID- 11970489
TI  - Energy-level statistics in the fine conformational resolution of RNA folding
      dynamics.
AB  - This work is aimed at determining the energy-level statistics of the fine
      resolution of soft-mode dynamics warranting an adiabatically simplified
      structural relaxation of a folding biopolymer chain. The parameters defining the
      intrabasin structure relaxation are specified for RNA, so that each Watson-Crick
      base-pairing pattern may be treated as a quasiequilibrium ensemble of substates
      or torsional isomers within relevant folding time scales. The temperature
      dependent threshold for energy dispersion associated with the fine structure of
      each superbasin is determined so as to warrant the adiabatic entrainment of the
      torsional dynamics.

PMID- 11970490
TI  - Reaction-diffusion waves of advance in the transition to agricultural economics.
AB  - In a previous paper [J. Fort and V. Mendez, Phys. Rev. Lett. 82, 867 (1999)], the
      possible importance of higher-order terms in a human population wave of advance
      has been studied. However, only a few such terms were considered. Here we develop
      a theory including all higher-order terms. Results are in good agreement with the
      experimental evidence involving the expansion of agriculture in Europe.

PMID- 11970491
TI  - On-line learning of unrealizable tasks.
AB  - The dynamics of on-line learning is investigated for structurally unrealizable
      tasks in the context of two-layer neural networks with an arbitrary number of
      hidden neurons. Within a statistical mechanics framework, a closed set of
      differential equations describing the learning dynamics can be derived, for the
      general case of unrealizable isotropic tasks. In the asymptotic regime one can
      solve the dynamics analytically in the limit of a large number of hidden neurons,
      providing an analytical expression for the residual generalization error, the
      optimal and critical asymptotic training parameters, and the corresponding
      prefactor of the generalization error decay.

PMID- 11970492
TI  - Diversity and extinction in a lattice model of a population with fluctuating
      environment.
AB  - I study a lattice stochastic model of a mutating population sensitive to the
      influence of a fluctuating environment. The dynamics of the population stressed
      by linear and periodic disturbances is investigated. In agreement with previous
      studies of nonspatial models, I find a critical rate of change in the
      environmental variable beyond which the population becomes extinct, and I show
      explicitly that the presence of space in the model can affect the critical rate.
      Further, I study the diversity defined as the total number of different cell
      types present in the lattice as a function of intensity and frequency of the
      environmental disturbance. If the disturbance becomes fast and intense the
      population becomes extinct. Interestingly, I find that for moderate stresses the
      diversity increases with the intensity and frequency of disturbance. The
      transition between large diversity and extinction is sharp, implying that the
      populations with high diversity are generally the ones closest to the extinction
      threshold. When subjected to colored noise of increasing intensity the system
      grows in diversity but at the same time is more likely to become extinct.

PMID- 11970494
TI  - Receiver operating characteristics of perceptrons: influence of sample size and
      prevalence.
AB  - In many practical classification problems it is important to distinguish false
      positive from false negative results when evaluating the performance of the
      classifier. This is of particular importance for medical diagnostic tests. In
      this context, receiver operating characteristic (ROC) curves have become a
      standard tool. Here we apply this concept to characterize the performance of a
      simple neural network. Investigating the binary classification of a perceptron we
      calculate analytically the shape of the corresponding ROC curves. The influence
      of the size of the training set and the prevalence of the quality considered are
      studied by means of a statistical-mechanics analysis.

PMID- 11970493
TI  - Modeling the effect of an external electric field on the velocity of spike
      propagation in a nerve fiber.
AB  - The effect of an externally generated electric field on the propagation of action
      potentials is modeled, assuming the Hodgkin-Huxley equation for the voltage
      dependent conductance of the membrane of a nerve fiber. With some simplifying
      assumptions, this conductance together with Maxwell's equations leads to the
      Hodgkin-Huxley differential equations for propagation, modified by a term
      proportional to the gradient of the externally generated electric field component
      along the nerve fiber. Computer solution of these equations shows the influence
      of an electric field gradient on propagation velocity. When the electric field
      oscillates, voltage spikes starting later along a given axon advance or lag
      relative to earlier spikes, so the time between spikes at the receiving end
      differs from the time between spike originations. The amount that a low-frequency
      electric field modulates pulse timing at the end of a fiber relative to that at
      the beginning is estimated under several conditions.

PMID- 11970495
TI  - Statistics of DNA sequences: a low-frequency analysis.
AB  - We study statistical properties of DNA chains of thirteen microbial complete
      genomes. We find that the power spectrum of several of the sequences studied
      flattens off in the low frequency limit. This implies the correlation length in
      those sequences is much smaller than the entire DNA chain. Consequently, in
      contradiction with previous studies, we show that the fractal behavior of DNA
      chains does not always prevail through the entire DNA molecule.

PMID- 11970496
TI  - Modified self-consistent harmonic approach to thermal fluctuational disruption of
      disulfide bonds in proteins.
AB  - Disulfide bonds (covalent bonds between two sulfur atoms on separate amino acid
      cysteines) play an important role in the folding stability of many proteins. The
      determination of the dynamic stability of disulfide bonds can therefore
      facilitate an understanding of the mechanism of protein stability. We have
      examined whether a modified self-consistent harmonic approach, which has been
      successful in modeling hydrogen bond breaking dynamics in DNA and covalent bond
      disruption in drug-DNA systems, is useful in computing thermal fluctuational
      disruption probability of disulfide bonds in proteins. Our results on a number of
      protein x-ray crystal structures showed that the computed disruption
      probabilities are consistent with observations. The free energies derived from
      computed probabilities are comparable to the observed values from protein
      engineering experiments. The method presented here has a potential application in
      analyzing disulfide bond dynamics in a variety of biological processes.

PMID- 11970497
TI  - Minimal model for complex dynamics in cellular processes.
AB  - Cellular functions are controlled and coordinated by the complex circuitry of
      biochemical pathways regulated by genetic and metabolic feedback processes. This
      paper aims to show, with the help of a minimal model of a regulated biochemical
      pathway, that the common nonlinearities and control structures present in
      biomolecular interactions are capable of eliciting a variety of functional
      dynamics, such as homeostasis, periodic, complex, and chaotic oscillations,
      including transients, that are observed in various cellular processes.

PMID- 11970498
TI  - Energy gain of injected electrons subjected to an intense laser field and its
      magnetic field induced in plasma.
AB  - Cyclotron-resonance energy gain of injected electrons subjected to an intense
      circularly polarized laser field and the magnetic field induced in a low-density
      plasma is investigated theoretically. By considering the inverse Faraday effect
      (IFE), where a circularly polarized finite area laser beam induces an axial
      magnetic field in a plasma, it is found that very interesting energy gains can be
      obtained by Doppler-shifted cyclotron resonance in this field for the appropriate
      injection velocity. This same IFE field also acts to confine these electrons
      radially and, on exiting the plasma adiabatically, it is in this way that the
      transverse electron energy is converted to axial energy. Two limits to the energy
      gain are discussed: (i) cyclotron radius of the energetic electrons becoming
      comparable to the beam, and (ii) axial dephasing.

PMID- 11970499
TI  - Charge-fluctuation-induced heating of dust particles in a plasma.
AB  - Random charge fluctuations are always present in dusty plasmas due to the
      discrete nature of currents charging the dust particle. These fluctuations can be
      a reason for the heating of the dust particle system. Such unexpected heating
      leading to the melting of the dust crystals was observed recently in several
      experiments. In this paper we show by analytical evaluations and numerical
      simulation that charge fluctuations provide an effective source of energy and can
      heat the dust particles up to several eV, in conditions close to experimental
      ones.

PMID- 11970500
TI  - Nonhomogeneity of dusty crystals and plasma diagnostics.
AB  - Real dusty crystals are inhomogeneous due to the presence of external forces. We
      suggest approximations for calculations of different types of inhomogeneous dust
      crystals (DC's) (chain and DC's with a few slabs) in the equilibrium state. The
      results are in a good agreement with experimental results and can be used as an
      effective diagnostic method for many dusty systems.

PMID- 11970501
TI  - Self-consistent model of a positive column in a glow discharge under free-flight
      and collisional regimes of charged-particle motion.
AB  - We consider the nonlocal theory of a positive column in a glow discharge in two
      cases, where the mean free path of charged particles is either greater than the
      discharge tube radius (the free-flight regime) or much less than the radius (the
      collisional regime). The great bulk of electrons, which determines the density
      and the discharge current in the axial direction, appears to be trapped by the
      radial field of a positive column. The electron flux to the wall, which
      compensates for the ionization in a volume, is determined by fast electrons with
      energies of the order of wall potential, which are able to leave in a loss cone.
      The electron kinetic equation, which is solved by averaging it over the radial
      transits for the two regimes considered, permits us to obtain the electron
      density and the ionization rate. Thus, we develop the theory of a positive column
      for the non-Boltzmann electron distribution in the radial field. Under the free
      flight regime, this theory is developed by analogy with the Langmuir-Tonks one.
      Under the collisional regime, the spatial distribution of the potential is
      obtained from the ion motion equation with the ambipolar diffusion coefficient,
      which depends on the radial coordinate. The concrete calculations are carried out
      for the xenon discharge under the free-flight and collisional regimes. The
      theoretical calculations are compared with the results of experiments on the
      measurements of the electric field and the densities of metastable and resonance
      xenon atoms.

PMID- 11970502
TI  - Forward and backward stimulated Brillouin scattering of crossed laser beams.
AB  - The simultaneous forward and backward stimulated Brillouin scattering (SBS) of
      crossed laser beams is studied in detail. Analytical solutions are obtained for
      the linearized equations governing the transient phase of the instability and the
      nonlinear equations governing the steady state. These solutions show that
      backward SBS dominates the initial evolution of the instability, whereas forward
      SBS dominates the steady state. The analysis of this paper is verified by
      numerical simulation.

PMID- 11970503
TI  - Ion explosion and multi-mega-electron-volt ion generation from an underdense
      plasma layer irradiated by a relativistically intense short-pulse laser.
AB  - Ion acceleration and expansion in the interaction of a relativistically intense
      short-pulse laser with an underdense plasma layer are investigated. Ion and
      electron dynamics are studied by a two-dimensional particle-in-cell simulation
      with the real mass ratio. It is shown that the longitudinal electric field
      induced by electron evacuation due to a large ponderomotive force or light
      pressure can accelerate ions to several MeV in the direction of the laser
      propagation. It is after the laser completely passes through the plasma layer
      that the ion explosion starts to be significant.

PMID- 11970504
TI  - Small-scale electron density and magnetic-field structures in the wake of an
      ultraintense laser pulse.
AB  - We investigate the interaction of a high intensity ultrashort laser pulse with an
      underdense collisionless plasma in the regime where the Langmuir wake wave
      excited behind the laser pulse is loaded by fast particle beams, formed during
      the wake wave breaking. The beam loading causes the deterioration of the central
      part of the wake wave near the pulse axis, and the formation of bunches of
      sharply focalized ultrarelativistic electrons. The bunches of electrons generate
      a fast propagating magnetic field, which we interpret in terms of the magnetic
      component of the Lienard-Wiechert potential of a moving electric charge.

PMID- 11970505
TI  - Radiation field in a superstrong magnetoactive electron plasma.
AB  - Using the language of quantum field theory, we present a concise derivation for
      the electromagnetic vector potential A(mu), which is valid for an anisotropic
      superstrong magnetoactive electron plasma. It is shown that the expression for
      the vector potential A(mu) can be reduced to various known limits. Applications
      to important problems in astrophysics are briefly discussed. The relevance of our
      result to the recent development of the collective interaction between intense
      neutrino fluxes and stellar plasmas is briefly stressed.

PMID- 11970506
TI  - Optical measurements of paired luminous rings in capacitive radio-frequency
      hydrogen discharges.
AB  - Optical measurements of paired luminous rings separated by a narrow dark gap have
      been conducted in capacitive radio-frequency (rf) hydrogen discharges. The lines
      of molecular H(2) are strongly excited at the ring emission compared with a
      weaker emission of the H(alpha) line. The number of ring pairs increases with gas
      pressure, and the outermost ring pairs near the electrodes start to appear
      earlier than the inner ones. Each ring emission is turning on and off with the
      applied rf frequency, i.e., the left-side (right-side) ring of a paired ring is
      on when the left-side (right-side) electrode is biased positively. The axial
      light intensity profile, which is time resolved with the applied rf frequency,
      indicates that the emission profiles are similar to those of dc glow discharges,
      and the luminous rings correspond to the standing striations at the positive
      column.

PMID- 11970507
TI  - Trace rare gases optical emission spectroscopy: nonintrusive method for measuring
      electron temperatures in low-pressure, low-temperature plasmas.
AB  - Trace rare gases optical emission spectroscopy (TRG-OES) is a new, nonintrusive
      method for determining electron temperatures (T(e)) and, under some conditions,
      estimating electron densities (n(e)) in low-temperature, low-pressure plasmas.
      The method is based on a comparison of atomic emission intensities from trace
      amounts of rare gases (an equimixture of He, Ne, Ar, Kr, and Xe) added to the
      plasma, with intensities calculated from a model. For Maxwellian electron energy
      distribution functions (EEDFs), T(e) is determined from the best fit of theory to
      the experimental measurements. For non-Maxwellian EEDFs, T(e) derived from the
      best fit describes the high-energy tail of the EEDF. This method was reported
      previously, and was further developed and successfully applied to several
      laboratory and commercial plasma reactors. It has also been used in
      investigations of correlations between high-T(e) and plasma-induced damage to
      thin gate oxide layers. In this paper, we provide a refined mechanism for the
      method and include a detailed description of the generation of emission from the
      Paschen 2p manifold of rare gases both from the ground state and through
      metastable states, a theoretical model to calculate the number density of
      metastables (n(m)) of the rare gases, a practical procedure to compute T(e) from
      the ratios of experimental-to-theoretical intensity ratios, a way to determine
      the electron density (n(e)), a discussion of the range of sensitivity of TRG-OES
      to the EEDF, and an estimate of the accuracy of T(e). The values of T(e) obtained
      by TRG-OES in a transformer-coupled plasma reactor are compared with those
      obtained with a Langmuir probe for a wide range of pressures and powers. The
      differences in T(e) from the two methods are explained in terms of the EEDF
      dependence on pressure.

PMID- 11970508
TI  - Beam coupling impedances for perforated beam pipes with general shape from
      impedance boundary conditions.
AB  - An equivalent wall impedance to describe the electromagnetic boundary conditions
      at perforated pipe walls is introduced. The new impedance boundary condition,
      together with general formulas for computing longitudinal and transverse beam
      coupling impedances in complex heterogeneous pipes, provides a good trade-off
      between computational accuracy and ease.

PMID- 11970509
TI  - Role of semiclassical description in the quantumlike theory of light rays.
AB  - An alternative procedure to the one by Gloge and Marcuse [J. Opt. Soc. Am. 59,
      1629 (1969)] for performing the transition from geometrical optics to wave optics
      in the paraxial approximation is presented. This is done by employing a recent
      "deformation" method used to give a quantumlike phase-space description of
      charged-particle-beam transport in the semiclassical approximation. By taking
      into account the uncertainty relation (diffraction limit) that holds between the
      transverse-beam-spot size and the rms of the light-ray slopes, the classical
      phase-space equation for light rays is deformed into a von Neumann-like equation
      that governs the phase-space description of the beam transport in the
      semiclassical approximation. Here, Planck's constant and the time are replaced by
      the inverse of the wave number, not lambda, and the propagation coordinate,
      respectively. In this framework, the corresponding Wigner-like picture is given
      and the quantumlike corrections for an arbitrary refractive index are considered.
      In particular, it is shown that the paraxial-radiation-beam transport can also be
      described in terms of a fluid motion equation, where the pressure term is
      replaced by a quantumlike potential in the semiclassical approximation that
      accounts for the diffraction of the beam. Finally, a comparison of this fluid
      model with Madelung's fluid model is made, and the classical-like picture given
      by the tomographic approach to radiation beams is advanced as a future
      perspective.

PMID- 11970510
TI  - Effects of overlapping parametric resonances on the particle diffusion process.
AB  - The evolution of the beam distribution in a double-rf system with a phase
      modulation on either the primary or secondary rf cavity was measured. We find
      that the particle diffusion process obeys the Einstein relation if the phase
      space becomes globally chaotic. When dominant parametric resonances still exist
      in the phase space, particles stream along the separatrices of the dominant
      resonance, and the beam width exhibits characteristic oscillatory structure. The
      particle-tracking simulations for the double-rf system are employed to reveal the
      essential diffusion mechanism. Coherent octupolar motion has been observed in the
      bunch beam excitation. The evolution of the longitudinal phase space in the
      octupole mode is displayed.

PMID- 11970511
TI  - Wakefield excitation in multimode structures by a train of electron bunches.
AB  - We discuss wakefield excitation and propagation in dielectric structures,
      particularly concentrating on the case of multiple drive beam excitation in
      multimoded structures. We emphasize calculations of the energy loss of the drive
      beam train, the amplitude of the wakefield, and the relationship between power
      flow and stored energy in the dielectric wakefield device. We show that for a
      collinear multimode structure the amplitude of the wakefield generated by a bunch
      train is less than or equal to the wakefield generated by a single bunch of the
      same total charge. Furthermore, the transformer ratio R is shown to be always
      less than 2, even in the multiple drive beam case.

PMID- 11970512
TI  - Addition formulas and the Rayleigh identity for arrays of elliptical cylinders.
AB  - We apply the Rayleigh method to solve the problem where a uniform electrostatic
      field is imposed upon a rectangular array of elliptical cylinders embedded in a
      matrix of unit dielectric constant. This new formulation overcomes geometric
      restrictions inherent in previous methods and is shown in principle and in
      various examples to converge for all possible geometries of the array and
      inclusion. Also presented are forms of both the interior and exterior addition
      formulas for harmonic functions in elliptical coordinates that possess optimal
      regions of convergence.

PMID- 11970514
TI  - Crescent singularities and stress focusing in a buckled thin sheet: mechanics of
      developable cones.
AB  - The localization of deformation is a simple consequence of the fact that bending
      a thin sheet is energetically cheaper than stretching it. In this paper we
      investigate conical singularities that appear on a crumpled sheet and called
      developable cones (d cones). We found that for a sample of a finite thickness the
      singularity is never pointlike but has a spatial extension in the form of a
      crescent. A further deformation of the d cone leads to a transition to a plastic
      deformation equivalent to a decrease in the singularity size characterized from
      curvature and profile analysis. The crescent radius of curvature is measured both
      at small deformations and at large deformations. It is found that, during the
      buckling process, the curvature of the crescent exhibits two different scalings
      versus the deformation. From the cone profile, we measured the reaction force of
      the plate to deformation; and from force measurements, the energy that is
      necessary to create the singularity is characterized.

PMID- 11970513
TI  - Resonances and localization of classical waves in random systems with correlated
      disorder.
AB  - An original approach to the description of classical wave localization in weakly
      scattering random media is developed. The approach accounts explicitly for the
      correlation properties of the disorder, and is based on the idea of spectral
      filtering. According to this idea, the Fourier space (power spectrum) of the
      scattering potential is divided into two different domains. The first one is
      related to the global (Bragg) resonances and consists of spectral components
      lying within a limiting sphere of the Ewald construction. These resonances,
      arising in the momentum space as a result of a self-averaging, determine the
      dynamic behavior of the wave in a typical realization. The second domain,
      consisting of the components lying outside the limiting sphere, is responsible
      for the effect of local (stochastic) resonances observed in the configuration
      space. Combining a perturbative path-integral technique with the idea of spectral
      filtering allows one to eliminate the contribution of local resonances, and to
      distinguish between possible stochastic and dynamical localization of waves in a
      given system with arbitrary correlated disorder. In the one-dimensional (1D)
      case, the result, obtained for the localization length by using such an indirect
      procedure, coincides exactly with that predicted by a rigorous theory. In higher
      dimensions, the results, being in agreement with general conclusions of the
      scaling theory of localization, add important details to the common picture. In
      particular, the effect of the high-frequency localization length saturation is
      predicted for 2D systems. Some possible links with the problem of wave transport
      in periodic or near-periodic systems (photonic crystals) are also discussed.

PMID- 11970515
TI  - Three-wave interaction in two-component quadratic nonlinear lattices.
AB  - We investigate a two-component lattice with a quadratic nonlinearity and find
      with the multiple scale technique that integrable three-wave interaction takes
      place between plane wave solutions when these fulfill resonance conditions. We
      demonstrate that energy conversion and pulse propagation known from three-wave
      interaction is reproduced in the lattice and that exact phase matching of
      parametric processes can be obtained in non-phase-matched lattices by tilting the
      interacting plane waves with respect to each other.

PMID- 11970516
TI  - Generation of multiple-charged optical vortex solitons in a saturable nonlinear
      medium.
AB  - Multiply charged optical vortex solitons (OVS) (m=1,...,4) are generated in a
      thermal nonlinear medium with saturation. The respective soliton constants are
      found to be linearly proportional to the topological charges. Special attention
      is paid to the modulational instability, which is effectively suppressed by a
      moderate saturation but still remains an increasing function of the topological
      charge. For the particular experimental conditions, the recorded OVS profiles are
      found to be in good qualitative agreement with the numerical stationary solutions
      of the generalized nonlinear Schrodinger equation.

PMID- 11970517
TI  - Effects of disorder on wave propagation in two-dimensional photonic crystals.
AB  - The electromagnetic transmittance of disordered two-dimensional photonic crystals
      composed of circular cylinders is investigated as a function of wavelength and
      polarization. At short wavelengths, the transmittance shows a band structure
      similar to that found in the optical absorption spectrum of amorphous
      semiconductors, with impurity states increasingly appearing on the long
      wavelength side of the band gaps as the degree of disorder is increased. In the
      long-wavelength limit, Anderson localization of waves is found, provided that the
      wavelength is not so large that the random photonic crystal can be viewed as
      homogeneous. The localization properties in this regime are studied and an
      analytic expression for the dependence of the localization length on wavelength
      is derived. In the limit of extremely long wavelengths, the system homogenizes
      and can be replaced by an equivalent one with uniform effective refractive index,
      whose form is derived for both polarizations. Analysis of the crossover between
      localization and homogenization is also presented.

PMID- 11970518
TI  - Multiparticle breathers for a chain with double-quadratic on-site potential.
AB  - We investigate the existence and properties of multiparticle breathers for a one
      dimensional model with harmonic nearest neighbor interactions where a group of r
      particles (r=1,2,3, ...) perform interwell oscillations between both wells of a
      double-quadratic on-site potential. We find two types of such breathers. For the
      first type the breather frequency Omega is within the single-particle oscillator
      spectrum, and the "residence" time of each breather particle in the left and
      right well is about the same. For the second breather Omega is below that
      spectrum, and the ratio tau(L)/tau(R) of the residence time in the left and right
      wells is different from zero, and takes approximately rational values like
      1/4,1/3,2/3,3/4, etc. This second type of breather occurs for two and more
      breather particles only.

PMID- 11970519
TI  - Dark and bright solitons in resonantly absorbing gratings.
AB  - We consider an optical medium consisting of a periodic refractive-index grating
      and a periodic set of thin layers of two-level systems resonantly interacting
      with the electromagnetic field. Recently, it has been shown that such a system
      gives rise to a vast variety of stable bright solitons. In this work, we
      demonstrate that the system has another very unusual property: stable bright
      solitons can coexist with stable continuous-wave (cw) states and stable dark
      solitons (DS's). Depending on the parameters' values, a DS frequency band
      coexists (without overlap) with one or two bright-soliton bands. Quiescent
      (standing) DS's are found in an analytical form, and moving ones are obtained
      numerically. Simulations show that a considerable part of the DS solutions are
      completely stable against arbitrary small perturbations. The fact that this
      system supports both stable bright and dark solitons for the same parameters
      values may find interesting applications in photonics.

PMID- 11970520
TI  - Discrete approximation of the linear Boolean model of heterogeneous materials.
AB  - The Boolean model is a random set process in which random shapes are positioned
      according to outcomes of a Poisson process. Two- and three-dimensional versions
      of the model characterize structures of certain heterogeneous materials. Linear
      transects of the Boolean model produce a one-dimensional Boolean model that
      summarizes some material properties. Two functions from linear transects, clump
      length and lineal path distributions, provide information on material phase
      connectivity. Computation of these distributions is notoriously difficult. We
      provide a discrete approximation to the one-dimensional convex-grain Boolean
      model that yields stable, linear-time, recursive algorithms to approximate these
      functions. Computer simulations demonstrate accuracy and speed.

PMID- 11970521
TI  - Stability of localized structures in the Swift-Hohenberg equation.
AB  - We show that nonmonotonic (oscillatory) decay of the boundaries of phase domains
      is crucial for the stability of localized structures in systems described by
      Swift-Hohenberg equation. The less damped (more oscillatory) are the boundaries,
      the larger are the existence ranges of the localized structures. For very weakly
      damped spatial oscillations, higher-order localized structures are possible.

PMID- 11970522
TI  - Oscillon formation as an initial pattern state.
AB  - Following Venkataramani and Ott [Phys. Rev. Lett. 80, 3495 (1998)], we consider
      oscillons (local excitations) as spatiotemporal subcritical bifurcation
      phenomena. We show in a series of numerical experiments that the appearance of
      oscillons is highly dependent on the initial pattern state. This finding has led
      to a new patterning mechanism. In this Brief Report we describe the instabilities
      that govern the mutual interaction of oscillons/extended patterns.

PMID- 11970523
TI  - Nonequilibrium roughening transition in an interface growth model with two
      species of particles.
AB  - We introduce an interface growth model exhibiting a roughening transition from a
      smooth to a rough phase, related to a nonequilibrium phase transition (NPT) from
      an active to an inactive phase at the bottom layer. In the model, two different
      species of particles are deposited or evaporated, and a dynamic rule is assigned
      symmetrically or asymmetrically with respect to particle species. It is found
      that for the asymmetric case, the roughening transition and the NPT belong to the
      directed percolation universality class, while for the symmetric case, they are
      related to the directed Ising universality class.

PMID- 11970524
TI  - Relativistic quantum thermodynamics of ideal gases in two dimensions.
AB  - In this work we study the behavior of relativistic ideal Bose and Fermi gases in
      two space dimensions. Making use of polylogarithm functions we derive a closed
      and unified expression for their densities. It is shown that both type of gases
      are essentially inequivalent, and only in the non-relativistic limit the spinless
      and equal mass Bose and Fermi gases are equivalent as known in the literature.

PMID- 11970525
TI  - Irreversible thermodynamics of Poisson processes with reaction.
AB  - A kinetic model is derived to study the successive movements of particles,
      described by a Poisson process, as well as their generation. The irreversible
      thermodynamics of this system is also studied from the kinetic model. This makes
      it possible to evaluate the differences between thermodynamical quantities
      computed exactly and up to second-order. Such differences determine the range of
      validity of the second-order approximation to extended irreversible
      thermodynamics.

PMID- 11970526
TI  - Efficient algorithm for detecting unstable periodic orbits in chaotic systems.
AB  - We present an efficient method for fast, complete, and accurate detection of
      unstable periodic orbits in chaotic systems. Our method consists of an iterative
      scheme and an effective technique for selecting initial points. The iterative
      scheme is based on the semi-implicit Euler method, which has both fast and global
      convergence, and only a small number of initial points is sufficient to detect
      all unstable periodic orbits of a given period. The power of our method is
      illustrated by numerical examples of both two- and four-dimensional maps.

PMID- 11970527
TI  - Unstable periodic orbits and the natural measure of nonhyperbolic chaotic
      saddles.
AB  - Chaotic saddles are nonattracting dynamical invariant sets that physically lead
      to transient chaos. We examine the characterization of the natural measure by
      unstable periodic orbits for nonhyperbolic chaotic saddles in dissipative
      dynamical systems. In particular, we compare the natural measure obtained from a
      long trajectory on the chaotic saddle to that evaluated from unstable periodic
      orbits embedded in it. Our systematic computations indicate that the periodic
      orbit theory of the natural measure, previously shown to be valid only for
      hyperbolic chaotic sets, is applicable to nonhyperbolic chaotic saddles as well.

PMID- 11970528
TI  - Asymptotic analysis of particle engulfmemt.
AB  - An asymptotic analysis is conducted on the interaction between an insoluble
      spherical particle and an advancing solid-liquid interface when the particle is
      in the near-contact region (gap thickness is much smaller than the particle's
      radius). The analysis considers only thermal effects in a pure substance. The
      interface equilibrium temperature includes the undercooling effects due to the
      front curvature and to the long-range intermolecular forces in the thin melt film
      behind the particle. An expression for the crystal-particle gap thickness is
      derived and used to calculate the threshold value for the front velocity V(T)
      which separates pushing from engulfment.

PMID- 11970529
TI  - Three-point velocity correlation functions in two-dimensional forced turbulence.
AB  - We present a simple exact formula for three-point velocity correlation functions
      in two-dimensional turbulence which is valid at all scales and which interpolates
      between the direct and inverse cascade regimes. As expected, these correlation
      functions are universal in these extreme regimes. We also discuss the effects of
      anisotropy and friction.

PMID- 11970530
TI  - Multistability and symmetry breaking in the two-dimensional flow around a square
      cylinder.
AB  - We use numerical methods to study two-dimensional flow passing a square cylinder
      at low Reynolds numbers, and observe period-1 and -3 vortices behind the cylinder
      at the same Reynolds number Re. When Re increases from a small number to a
      critical value Re(c) approximately equal to 320, the system could change from
      bistability, which maintains the spatial symmetry, to tristability, which breaks
      the spatial symmetry. Our results suggest many interesting problems for further
      studies.

PMID- 11970531
TI  - General solution for the Couette flow profile.
AB  - A general solution for the Couette velocity profile is reported. Taylor's
      classical one-dimensional profile is shown to be a special case of this solution
      for configurations whose aspect ratio is large. Numerical evaluation indicates
      that error between the two profiles is a logarithmic function of the aspect ratio
      and provides data to estimate when Taylor's profile should be replaced with the
      present solution.

PMID- 11970532
TI  - Micellar shape anisotropy and elastic constants in discotic lyotropic liquid
      crystals.
AB  - The elastic constants of a discotic lyotropic nematic liquid crystal are
      calculated by means of a pseudomolecular approach as functions of the micellar
      shape anisotropy. By assuming that the temperature dependence of the ratio of the
      elastic constants comes from the temperature dependence of the micellar shape
      anisotropy, the theoretical predictions are connected with experimental
      measurements for the ratio K(33)/K(11). This procedure permits one to determine,
      in a phenomenological way, the temperature dependence for the ratio of elastic
      constants and for the micellar shape anisotropy near the nematic-isotropic
      transition in agreement with the experimental data.

PMID- 11970533
TI  - Granular boycott effect: how to mix granulates.
AB  - Granular material can display the basic features of the Boycott effect in
      sedimentation. A simple experiment shows that granular material falls faster in
      an inclined tube than in a vertical tube, in analogy with the Boycott effect. As
      long as the inclination of the tube is above the avalanche threshold, descent of
      granular material in the tube causes internal convection which in turn results in
      an efficient mixture of the granular components. By contrast, as in analogous
      experiments in two dimensions, a vertical fall of granular material occurs via
      successive block fragmentation, resulting in poor mixing.

PMID- 11970534
TI  - Influence of particle size on diffusion-limited aggregation.
AB  - The influence of particle size on diffusion-limited aggregation (DLA) has been
      investigated by computer simulations. For DLA clusters consisting of two kinds of
      particles with different sizes, when large particles are in the minority, the
      patterns of clusters appear asymmetrical and nonuniform, and their fractal
      dimensions D(f) increase compared with one-component DLA. With increasing size of
      large particles, D(f) increases. This increase can be attributed to two reasons:
      one is that large particles become new growth centers; the other is the big
      masses of large particles. As the concentration ratio x(n) of large particles
      increases, D(f) will reach a maximum value D(f(m)) and then decrease. When x(n)
      exceeds a certain value, the morphology and D(f) of the two-component DLA
      clusters are similar to those of one-component DLA clusters.

PMID- 11970535
TI  - Addendum to "Quantitative measure of folding in two-dimensional polymers".
AB  - Recently, we introduced a measure of folding complexity for two-dimensional
      polymers, N macro, the mean radial intersection number [Phys. Rev. E 59, 4209
      (1999)]. In this addendum, we expand on three aspects of the previous work.
      First, we provide an analytical expression for N macro that is valid for two
      dimensional networks. Second, we show that the power-law scaling N macro
      approximately equal to n(beta), with n the number of monomers, has a different
      critical exponent for random and self-avoiding walks. Finally, we find that the
      folding features in optimized projections of experimental three-dimensional
      (native) protein backbones fall between the latter limit models.

PMID- 11970536
TI  - Excitation of nonlinear two-dimensional wake waves in radially nonuniform plasma.
AB  - It is shown that an undesirable curvature of the wave front of a two-dimensional
      nonlinear wake wave, excited in uniform plasma by a relativistic charged bunch or
      laser pulse, may be compensated by radial change of the equilibrium plasma
      density.

PMID- 11970537
TI  - Grating transition radiation: a source of quasimonochromatic radiation.
AB  - We have observed transition radiation at optical wavelengths, emitted by 3-13-MeV
      electrons interacting with a diffraction grating. Near the direction of specular
      reflection we observed broadband radiation with the same properties as optical
      transition radiation from a flat surface. In addition, at large angles with
      respect to this direction and for low angles of incidence of the electrons on the
      grating surface, we observed the emission of quasimonochromatic radiation. This
      grating transition radiation may offer an alternative method for production of
      quasimonochromatic radiation in the far-infrared to mm wavelength range.

PMID- 11970538
TI  - Breather compactons in nonlinear Klein-Gordon systems.
AB  - We demonstrate the existence of a localized breathing mode with a compact
      support, i.e., a stationary breather compacton, in a nonlinear Klein-Gordon
      system. This breather compacton results from a delicate balance between the
      harmonicity of the substrate potential and the total nonlinearity induced by the
      substrate potential and the coupling forces between adjacent lattice sites.

PMID- 11970539
TI  - Dynamics of formation and interaction of photorefractive screening solitons.
AB  - An experimental and numerical investigation of the dynamical, time-dependent
      effects accompanying the formation and interaction of two-dimensional spatial
      screening solitons in a photorefractive strontium barium niobate crystal is
      performed. These effects include initial diffraction, collapse to the soliton
      shape, the oscillation of beam diameters, beam bending, and the rotation,
      twisting, and turning of soliton pairs. The dynamics of complex spiraling of two
      incoherent solitons is considered in more detail.

PMID- 11970540
TI  - Time diffraction of evanescent waves.
AB  - The concept of time diffraction of evanescent electromagnetic waves is proposed.
      Transient propagation of electromagnetic waves is studied in two forms:
      propagating and evanescent waves. Differences and similarities between quantum
      particle tunneling and photon tunneling are clearly demonstrated. Traversal time
      cannot be accurately defined due to diffraction in time. Nevertheless, a delay
      time is defined as the difference between the time of flight and the peak time of
      the transient light. The delay time is found to increase linearly and slowly with
      the traversal distance. Superluminal tunneling is found possible only for
      evanescent waves, and Einstein causality is not violated.

PMID- 11970541
TI  - Metastability for delayed differential equations.
AB  - In systems at phase transitions, two phases of the same substance may coexist for
      a long time before one of them dominates. We show that a similar phenomenon
      occurs in systems with delayed feedback, where short-term stable oscillatory
      patterns can also have very long lifetimes before vanishing into constant or
      periodic steady states.

PMID- 11970542
TI  - Comment on "Model for transmission of ultrastrong laser pulses through thin foil
      targets".
AB  - By discussing the results of Yu et al. [Phys. Rev. E 59, 3583 (1999)] on the near
      total transmission of laser pulses through highly overdense plasma foils, we show
      that they actually cannot explain the experimental results of Giulietti et al.
      [Phys. Rev. Lett. 79, 3194 (1997)]. Simple analytical calculations as well as
      particle-in-cell simulations support our assertion.

PMID- 11970544
TI  - Line shape measurement and isolated line width calculations: quantal versus
      semiclassical methods.
AB  - In a recent paper Griem, Ralchencko, Bray [Phys. Rev. E 56, 7186 (1998)] perform
      quantum-mechanical calculations of the line width of the B III 2s-2p transition
      and find agreement with previous quantum-mechanical results. The quantum
      mechanical widths are a factor approximately 2 smaller than those measured in a
      recent experiment where the full width at half maximum for the B III 2s-2p
      transition was measured in a plasma with a measured electron temperature and
      density of 10 eV and 2 x 10(18) cm(-3). The quantum-mechanical results also
      disagree with a nonperturbative semiclassical calculation. We will illustrate
      that Griem, Ralchencko, and Bray are incorrect in stating that the experimental
      results are in error and that the semiclassical calculations are inapplicable.

PMID- 11970546
TI  - Identity of the universal repulsive-core singularity with Yang-Lee edge
      criticality.
AB  - Lattice and continuum fluid models with repulsive-core interactions typically
      display a dominant, critical-type singularity on the real, negative activity
      axis. Lai and Fisher recently suggested, mainly on numerical grounds, that this
      repulsive-core singularity is universal and in the same class as the Yang-Lee
      edge singularities, which arise above criticality at complex activities with
      positive real part. A general analytic demonstration of this identification is
      presented here using a field-theory approach with separate representations of the
      repulsive and attractive parts of the pair interactions.

PMID- 11970547
TI  - Noise-induced oscillation and stochastic resonance in an autonomous chemical
      reaction system.
AB  - An autonomous three-variable chemical reaction model, which has been developed to
      describe kinetic oscillations in the NO+CO reaction, subjected to external
      parametric noise, is investigated. Noise-induced coherent oscillations (NICO's)
      in the absence of deterministic oscillations are observed near supercritical Hopf
      bifurcation points, and the NICO strength goes through a maximum with increments
      of noise intensity, characteristic of the occurrence of stochastic resonance. On
      the other hand, these phenomena do not appear if the limit cycle is created by a
      saddle-loop bifurcation.

PMID- 11970548
TI  - Decay of unstable equilibrium and nonequilibrium states with inverse probability
      current taken into account.
AB  - We study the causes of noise delayed decay of unstable states in nonlinear
      dynamic systems within the framework of the overdamped Brownian motion model. For
      the analysis, we use the exact expressions for the decay times of unstable
      states, which take into account the inverse probability current in contrast to
      the well-known mean first passage time method. These expressions are valid for
      any intensity of fluctuations and for arbitrary potential profiles. The effect of
      delay is shown to arise under the decay of unstable nonequilibrium states due to
      the action of two different mechanisms. These mechanisms are caused by the
      inverse probability current and by the nonlinearity of potential describing an
      unstable state.

PMID- 11970549
TI  - Effective action for stochastic partial differential equations.
AB  - Stochastic partial differential equations (SPDEs) are the basic tool for modeling
      systems where noise is important. SPDEs are used for models of turbulence,
      pattern formation, and the structural development of the universe itself. It is
      reasonably well known that certain SPDEs can be manipulated to be equivalent to
      (nonquantum) field theories that nevertheless exhibit deep and important
      relationships with quantum field theory. In this paper we systematically extend
      these ideas: We set up a functional integral formalism and demonstrate how to
      extract all the one-loop physics for an arbitrary SPDE subject to arbitrary
      Gaussian noise. It is extremely important to realize that Gaussian noise does not
      imply that the field variables undergo Gaussian fluctuations, and that these
      nonquantum field theories are fully interacting. The limitation to one loop is
      not as serious as might be supposed: Experience with quantum field theories
      (QFTs) has taught us that one-loop physics is often quite adequate to give a good
      description of the salient issues. The limitation to one loop does, however,
      offer marked technical advantages: Because at one loop almost any field theory
      can be rendered finite using zeta function technology, we can sidestep the
      complications inherent in the Martin-Siggia-Rose formalism (the SPDE analog of
      the Becchi-Rouet-Stora-Tyutin formalism used in QFT) and instead focus attention
      on a minimalist approach that uses only the physical fields (this "direct
      approach" is the SPDE analog of canonical quantization using physical fields).
      After setting up the general formalism for the characteristic functional
      (partition function), we show how to define the effective action to all loops,
      and then focus on the one-loop effective action and its specialization to
      constant fields: the effective potential. The physical interpretation of the
      effective action and effective potential for SPDEs is addressed and we show that
      key features carry over from QFT to the case of SPDEs. An important result is
      that the amplitude of the two-point function governing the noise acts as the loop
      counting parameter and is the analog of Planck's constant in this SPDE context.
      We derive a general expression for the one-loop effective potential of an
      arbitrary SPDE subject to translation-invariant Gaussian noise, and compare this
      with the one-loop potential for QFT.

PMID- 11970550
TI  - Percolation thresholds, critical exponents, and scaling functions on planar
      random lattices and their duals.
AB  - The bond-percolation process is studied on periodic planar random lattices and
      their duals. The thresholds and critical exponents of the percolation transition
      are determined. The scaling functions of the percolating probability, the
      existence probability of the appearance of percolating clusters, and the mean
      cluster size are also calculated. The simulation result of the percolation
      threshold is p(c)=0.3333+/-0.0001 for planar random lattices, and 0.6670+/-0.0001
      for the duals of planar random lattices. We conjecture that the exact value of
      p(c) is 1/3 for a planar random lattice and 2/3 for the dual of a planar random
      lattice. By taking possible errors into account, the results of our critical
      exponents agree with the values given by the universality hypothesis. By properly
      adjusting the metric factors on random lattices and their duals, we demonstrate
      explicitly that the idea of a universal scaling function with nonuniversal metric
      factors in the finite-size scaling theory can be extended to random lattices and
      their duals for the existence probability, the percolating probability, and the
      mean cluster size.

PMID- 11970551
TI  - Purity and decoherence in the theory of a damped harmonic oscillator.
AB  - For the generalized master equations derived by Karrlein and Grabert for the
      microscopic model of a damped harmonic oscillator, the conditions for purity of
      states are written, in particular for different initial conditions and different
      types of damping, including Ohmic, Drude, and weak coupling cases, and the
      Agarwal and Weidlich-Haake models. It is shown that the states which remain pure
      are the squeezed states with variances that are constant in time. For pure
      states, generalized nonlinear Schrodinger-type equations corresponding to these
      master equations are also obtained. Then the condition for purity of states of a
      damped harmonic oscillator is considered in the framework of Lindblad theory for
      open quantum systems. For a special choice of the environment coefficients,
      correlated coherent states with constant variances and covariance are shown to be
      the only states which remain pure all the time during the evolution of the
      considered system. In Karrlein-Grabert and Lindblad models, as well as in the
      particular models considered, expressions for the rate of entropy production are
      written, and it is shown that state which preserve their purity in time are also
      states which minimize entropy production and, therefore, are the most stable
      state under evolution in the presence of the environment, and play an important
      role in the description of decoherence phenomenon.

PMID- 11970552
TI  - Two-particle problem in a nonequilibrium many-particle system.
AB  - The two-particle problem within a nonequilibrium many-particle system is
      investigated in the framework of real-time Green's functions. Starting from the
      nonequilibrium Bethe-Salpeter equation on the Keldysh contour, a Dyson equation
      is given for two-time two-particle Green's functions. Thereby the well-known
      Kadanoff-Baym equations are generalized to the case of two-particle functions.
      The two-time structure of the equations is achieved in an exact way using the
      semigroup property of the free-particle propagators. The frequently used Shindo
      approximation is thus avoided. It turns out that results obtained earlier are
      valid only in limiting cases of a nondegenerate system or a static interaction,
      respectively. For the case of thermodynamic equilibrium, the differences to
      former results obtained for the effective two-particle Hamiltonian are discussed.

PMID- 11970553
TI  - Stabilization and enhancement of traffic flow by the next-nearest-neighbor
      interaction.
AB  - The car-following model of traffic is extended to take into account the car
      interaction before the next car ahead (the next-nearest-neighbor interaction).
      The traffic behavior of the extended car-following model is investigated
      numerically and analytically. It is shown that the next-nearest-neighbor
      interaction stabilizes the traffic flow. The jamming transition between the
      freely moving and jammed phases occurs at a higher density than the threshold of
      the original car-following model. By increasing the maximal velocity, the traffic
      current is enhanced without jam by the stabilization effect. The jamming
      transition is analyzed with the use of the linear stability and nonlinear
      perturbation methods. The traffic jam is described by the kink solution of the
      modified Korteweg-de Vries equation. The theoretical coexisting curve is in good
      agreement with the simulation result.

PMID- 11970554
TI  - Nonequilibrium noise in coupled phase oscillators.
AB  - The effect of nonequilibrium fluctuations on coupled phase oscillators is studied
      in a basic model. Its extremely rich behavior, including first and second order
      phase transitions, time-periodic phases, multiple anomalous hystereses, negative
      mobility, and other remarkable response properties, is unraveled by both
      analytical and numerical calculations.

PMID- 11970555
TI  - Coherence resonance in excitable and oscillatory systems: the essential role of
      slow and fast dynamics.
AB  - Stochastic noise of an appropriate amplitude can maximize the coherence of the
      dynamics of certain types of excitable systems via a phenomenon known as
      coherence resonance (CR). In this paper we demonstrate, using a simple excitable
      system, the mechanism underlying the generation of CR. Using analytical
      expressions for the spectral density of the system's dynamics, we show that CR
      relies on the coexistence of fast and slow motions. We also show that the same
      mechanism of CR holds in the oscillatory regime, and we examine how CR depends on
      both the excitability of the system and the nonuniformity of the motion.

PMID- 11970556
TI  - Bosonization, vicinal surfaces, and hydrodynamic fluctuation theory.
AB  - Through a Euclidean path integral we establish that the density fluctuations of a
      Fermi fluid in one dimension are related to vicinal surfaces and to the
      stochastic dynamics of particles interacting through long range forces with
      inverse distance decay. In the surface picture one easily obtains the Haldane
      relation, and identifies the scaling exponents governing the low energy,
      Luttinger liquid behavior. For the stochastic particle model we develop a
      hydrodynamic fluctuation theory, through which in some cases the large distance
      Gaussian fluctuations are proved nonperturbatively.

PMID- 11970557
TI  - Mobility and stochastic resonance in spatially inhomogeneous systems.
AB  - The mobility of an overdamped particle, in a periodic potential tilted by a
      constant external field and moving in a medium with periodic friction coefficient
      is examined. When the potential and the friction coefficient have the same
      periodicity but have a phase difference, the mobility shows many interesting
      features as a function of the applied force, the temperature, etc. The mobility
      shows stochastic resonance even for constant applied force, an issue of much
      recent interest. The mobility also exhibits a resonance-like phenomenon as a
      function of the field strength and noise induced slowing down of the particle in
      an appropriate parameter regime.

PMID- 11970558
TI  - Interacting spiral waves in the Oregonator model of the light-sensitive Belousov
      Zhabotinskii reaction.
AB  - We study the interaction of meandering spiral waves within the framework of a
      modified Oregonator model for the light-sensitive Belousov-Zhabotinskii medium.
      In this medium the local excitation threshold can be controlled by varying the
      intensity of incident light. At low as well as sufficiently high light intensity
      we find stable axis-symmetric bound states consisting of two counter-rotating
      spirals. At intensity values in between, spiral pairs undergo a symmetry-breaking
      instability, leading to one spiral suppressing and expelling the other. To avoid
      the instability, we consider a spiral wave interacting with its mirror image
      close to a plane boundary impermeable to diffusion. The drift velocity and the
      drift direction of those pseudobound states parallel to the boundary are strongly
      influenced by the light intensity.

PMID- 11970559
TI  - Levy diffusion as an effect of sporadic randomness.
AB  - The Levy diffusion processes are a form of non-ordinary statistical mechanics
      resting, however, on the conventional Markov property. As a consequence of this,
      their dynamic derivation is possible provided that (i) a source of randomness is
      present in the corresponding microscopic dynamics and (ii) the consequent process
      of memory erasure is properly taken into account by the theoretical treatment.

PMID- 11970560
TI  - Escape over a fluctuating barrier with additive and multiplicative noise.
AB  - The mean first passage time (MFPT) over the fluctuating potential barrier is
      investigated in the presence of additive and multiplicative noises. It is shown
      that the MFPT over the fluctuating potential barrier displays a resonant
      activation (RA). The effect of the additive and multiplicative noises and the
      correlation between them on the RA is that the additive and multiplicative noises
      can weaken the RA; but the correlation between them can enhance it. The
      susceptibility of the RA to the multiplicative noise is far larger than that to
      the additive one. In addition, we find that the transition rate (i.e., the
      inverse of the MFPT) over the fluctuating potential barrier can be suppressed by
      the positive correlation and show a minimum as the function of the noises'
      strengths.

PMID- 11970561
TI  - Fracture patterns induced by desiccation in a thin layer.
AB  - We study a theoretical model of mud cracks, that is, the fracture patterns
      resulting from the contraction with drying in a thin layer of a mixture of
      granules and water. In this model, we consider the slip on the bottom of this
      layer and the relaxation of the elastic field that represents deformation of the
      layer. Analysis of the one-dimensional model gives results for the crack size
      that are consistent with experiments. We propose an analytical method of
      estimation for the growth velocity of a simple straight crack to explain the very
      slow propagation observed in actual experiments. Numerical simulations reveal the
      dependence of qualitative nature of the formation of crack patterns on material
      properties.

PMID- 11970562
TI  - Exactly solvable two-way traffic model with ordered sequential update.
AB  - Within the formalism of the matrix product ansatz, we study a two-species
      asymmetric exclusion process with backward and forward site-ordered sequential
      updates. This model, which was originally introduced with the random sequential
      update [J. Phys. A 30, 8497 (1997)], describes a two-way traffic flow with a
      dynamic impurity and shows a phase transition between the free flow and the
      traffic jam. We investigate characteristics of this jamming and examine
      similarities and differences between our results and those with a random
      sequential update.

PMID- 11970563
TI  - Single-vehicle data of highway traffic: a statistical analysis.
AB  - In the present paper, single-vehicle data of highway traffic are analyzed in
      great detail. By using the single-vehicle data directly, empirical time headway
      distributions and speed-distance relations can be established. Both quantities
      yield relevant information about the microscopic states. Several fundamental
      diagrams are also presented, which are based on time-averaged quantities and
      compared with earlier empirical investigations. In the remaining part, time
      series analyses of the averaged as well as the single-vehicle data are carried
      out. The results will be used in order to propose objective criteria for an
      identification of the different traffic states, e.g., synchronized traffic.

PMID- 11970564
TI  - Geometry, thermodynamics, and finite-size corrections in the critical Potts
      model.
AB  - We establish an intriguing connection between geometry and thermodynamics in the
      critical q-state Potts model on two-dimensional lattices, using the q-state bond
      correlated percolation model (QBCPM) representation. We find that the number of
      clusters <N(c)> of the QBCPM has an energy-like singularity for q not equal to 1,
      which is reached and supported by exact results, numerical simulation, and
      scaling arguments. We also establish that the finite-size correction to the
      number of bonds, <N(b)>, has no constant term and explains the divergence of
      related quantities as q-->4, the multicritical point. Similar analyses are
      applicable to a variety of other systems.

PMID- 11970565
TI  - Percolation threshold of correlated two-dimensional lattices.
AB  - Previous simulations of percolation on correlated square and cubic lattices
      [Phys. Rev. E 56, 6586 (1997)] have been extended to all of the common two
      dimensional lattices, including triangular, square 1-2, honeycomb, and kagome.
      Simulations were performed on lattices of up to 1024x1024 sites. The results are
      independent of lattice size except, possibly, for a weak dependence at large
      correlation lengths. As in the previous studies, all results can be fit by a
      Gaussian function of the correlation length w, p(c)=p(infinity)(c)+(p(0)(c)
      p(infinity)(c))e(-alpha w(2)). However, there is some evidence that this fit is
      not theoretically significant. For the self-matching triangular and the matching
      square and square 1-2 lattices, the percolation thresholds satisfy the Sykes
      Essam relation p(c)(L)+p(c)(L*)=1.

PMID- 11970567
TI  - Sorting single events: mean arrival times of N random walkers.
AB  - Using a scaling approach we investigate the first passage time < mu(1,N)(r)> for
      the first out of N identical independently diffusing particles in ordered and
      disordered structures. For Euclidean spaces we obtain < mu(1,N)(r)> in terms of a
      series in (ln N)(-1), independent of dimension. In the case of disordered
      ramified fractals < mu(1,N)(r)> is expressed in terms of a series in (ln N)((1
      d(l)(w))), where d(l)(w) describes how the mean topological distance <l(t)>
      evolves with time t. We propose a scaling behavior for the related quantity
      S(N)(t), the number of distinct sites visited by N particles. We verify our
      predictions by numerical simulations.

PMID- 11970566
TI  - Thermally activated escape rates of uniaxial spin systems with transverse field:
      uniaxial crossovers.
AB  - Classical escape rates of uniaxial spin systems are characterized by a prefactor
      differing from and much smaller than that of the particle problem, since the
      maximum of the spin energy is attained everywhere on the line of constant
      latitude: theta =const, 0 < or= phi < or = 2 pi. If a transverse field is
      applied, a saddle point of the energy is formed, and high, moderate, and low
      damping regimes (similar to those for particles) appear. Here we present the
      first analytical and numerical study of crossovers between the uniaxial and other
      regimes for spin systems. It is shown that there is one HD-Uniaxial crossover,
      whereas at low damping the uniaxial and LD regimes are separated by two
      crossovers.

PMID- 11970568
TI  - Potential energy landscape of a model glass former: thermodynamics,
      anharmonicities, and finite size effects.
AB  - It is possible to formulate the thermodynamics of a glass forming system in terms
      of the properties of inherent structures, which correspond to the minima of the
      potential energy and build up the potential energy landscape in the high
      dimensional configuration space. In this work we quantitatively apply this
      general approach to a simulated model glass-forming system. We systematically
      vary the system size between N=20 and N=160. This analysis enables us to
      determine for which temperature range the properties of the glass former are
      governed by the regions of the configuration space, close to the inherent
      structures. Furthermore, we obtain detailed information about the nature of
      anharmonic contributions. Moreover, we can explain the presence of finite size
      effects in terms of specific properties of the energy landscape. Finally,
      determination of the total number of inherent structures for very small systems
      enables us to estimate the Kauzmann temperature.

PMID- 11970569
TI  - Scaling of the distribution of price fluctuations of individual companies.
AB  - We present a phenomenological study of stock price fluctuations of individual
      companies. We systematically analyze two different databases covering securities
      from the three major U.S. stock markets: (a) the New York Stock Exchange, (b) the
      American Stock Exchange, and (c) the National Association of Securities Dealers
      Automated Quotation stock market. Specifically, we consider (i) the trades and
      quotes database, for which we analyze 40 million records for 1000 U.S. companies
      for the 2-yr period 1994-95; and (ii) the Center for Research and Security Prices
      database, for which we analyze 35 million daily records for approximately 16,000
      companies in the 35-yr period 1962-96. We study the probability distribution of
      returns over varying time scales Delta t, where Delta t varies by a factor of
      approximately 10(5), from 5 min up to approximately 4 yr. For time scales from 5
      min up to approximately 16 days, we find that the tails of the distributions can
      be well described by a power-law decay, characterized by an exponent 2.5 <
      proportional to < 4, well outside the stable Levy regime 0 < alpha < 2. For time
      scales Delta t >> (Delta t)(x) approximately equal to 16 days, we observe results
      consistent with a slow convergence to Gaussian behavior. We also analyze the role
      of cross correlations between the returns of different companies and relate these
      correlations to the distribution of returns for market indices.

PMID- 11970570
TI  - Long-range electrostatic interactions between like-charged colloids: steric and
      confinement effects.
AB  - Within the framework of a modified Poisson-Boltzmann theory accounting for steric
      effects of microions, we prove analytically that the effective pair interactions
      between like-charge colloids immersed in a confined electrolyte are repulsive.
      Our approach encompasses and extends previously known results to the case of
      complete confinement, and further incorporates the finite size of the microions
      which is absent in the standard Poisson-Boltzmann theory.

PMID- 11970571
TI  - Universal renormalization of saddle-point integrals for condensed Bose gases.
AB  - When treating the ground-state contribution exactly, a variant of the saddle
      point method emerges that works even for condensed Bose gases. Results thus
      obtained, such as canonical partition functions, differ by universal
      renormalization factors from those provided by the conventional but incorrect
      scheme. The amended method yields the statistical properties of ideal and very
      weakly interacting Bose gases with a fixed number of particles with particular
      simplicity.

PMID- 11970572
TI  - Cyclotron resonance line shape function from the equilibrium density projection
      operator technique.
AB  - In this work, we present the calculation processes for obtaining the scattering
      factor for an electron-phonon system using the equilibrium density projection
      operator technique. We introduce two useful identities necessary to expand the
      scattering factor. We derive a cancellation relation which simplifies the
      expansion of the scattering factor. We obtain the cyclotron resonance line shape
      function in the case of weak interaction. Finally, we compare our results with
      other theories.

PMID- 11970573
TI  - Electrolytic depletion interactions.
AB  - We consider the interactions between two uncharged planar macroscopic surfaces,
      immersed in an electrolyte solution, which are induced by interfacial
      selectivity. These forces are taken into account by introducing a depletion free
      energy density functional, in addition to the usual mean-field Poisson-Boltzmann
      functional. The minimization of the total free-energy functional yields the
      density profiles of the microions and the electrostatic potential. The disjoining
      pressure is obtained by differentiation of the total free energy with respect to
      the separation of the surfaces, holding the range and strength of the depletion
      forces constant. We find that the induced interaction between the two surfaces is
      always repulsive for sufficiently large separations, and becomes attractive at
      shorter separations. The nature of the induced interactions changes from
      attractive to repulsive at a distance corresponding to the range of the depletion
      forces.

PMID- 11970574
TI  - Loss of lag synchronization in coupled chaotic systems.
AB  - Lag synchronization denotes a particular form of synchronization in which the
      amplitudes of two interacting, nonidentical chaotic oscillators are correlated
      but there is a characteristic time delay between them. We study transitions to
      and between different forms of synchronization for the attractors defined as "in
      phase" and "out-of-phase" and investigate the processes by which lag
      synchronization is lost in two coupled Rossler systems. With a small frequency
      mismatch between the two systems, these processes are related to the occurrence
      of a peculiar form of basin structure as more and more periodic orbits embedded
      into the synchronized chaotic state become unstable in a transverse direction.

PMID- 11970575
TI  - Coupling of low-frequency modes with the complex Ginzburg-Landau equation:
      Generalized Zakharov equations.
AB  - In this paper we introduce and examine a generalization of the complex Ginzburg
      Landau equation (CGLE) where the self-interaction contained in the cubic term is
      replaced by a coupling involving the original field and a low-frequency one. New
      instabilities arise and a radically new asymptotic dynamical behavior emerges
      displaying defect turbulence over wide regions of the parameter space.

PMID- 11970576
TI  - Frozen spatial chaos induced by boundaries.
AB  - We show that rather simple but nontrivial boundary conditions could induce the
      appearance of spatial chaos (that is stationary, stable, but spatially disordered
      configurations) in extended dynamical systems with very simple dynamics. We
      exemplify the phenomenon with a nonlinear reaction-diffusion equation in a two
      dimensional undulated domain. Concepts from the theory of dynamical systems, and
      a transverse-single-mode approximation are used to describe the spatially chaotic
      structures.

PMID- 11970577
TI  - Excitability and coherence resonance in lasers with saturable absorber.
AB  - We show that a laser with a saturable absorber, described by the Yamada model,
      displays excitability just below threshold. A small perturbation, for example, a
      small input pulse, can trigger a single high output pulse, after which the system
      relaxes back to the off state. In order to study possible applications, such as
      pulse reshaping and clock recovery, approximate expressions are given for the
      excitability threshold and the delay between input and output pulses. Under the
      influence of optical noise, the system displays coherence resonance: below
      threshold the laser produces pulse trains with minimal jitter for a particular
      optimal noise level. This all-optical coherence resonance allows direct
      experimental verification.

PMID- 11970578
TI  - Chaotic alternation of waves in ring lasers.
AB  - We intend to give an analytic description of the mechanisms involved in the
      periodic and chaotic wave alternation frequently observed in ring lasers. A set
      of amplitude equations is derived from the Maxwell-Bloch equations. These
      equations are studied analytically and numerically.

PMID- 11970579
TI  - Recovery process of low-frequency fluctuations in laser diodes with external
      optical feedback.
AB  - The recovery process of low-frequency fluctuations is experimentally investigated
      in a semiconductor laser with external optical feedback. Monotonic stepwise
      increase of the light output intensity is observed for various external cavity
      lengths. The time interval of each step corresponds to the round-trip time of the
      external cavity. Transitions between steps and dynamics within each step are
      analyzed. Experimental results are discussed with reference to the scenario of
      chaotic mode itinerancy. Statistical properties of time intervals between power
      dropout events are also discussed.

PMID- 11970580
TI  - Numerical evidence for the existence of a low-dimensional attractor and its
      implications in the rheology of dilute suspensions of periodically forced slender
      bodies.
AB  - We provide numerical evidence for the existence of a low-dimensional chaotic
      attractor in the rheology of dilute suspensions of slender bodies in a simple
      shear flow. The rheological parameters which characterize the stress deformation
      behavior of the suspension are calculated based on appropriate averages over the
      orientation vectors of the slender bodies. The system considered in this work,
      therefore, exhibits chaos in experimentally measurable averages over a large
      number of uncoupled chaotic oscillators. The numerical demonstration that these
      parameters may evolve chaotically may thus have important consequences for both
      chaos theory and suspension rheology. We also provide plausible explanations for
      the existence of a low-dimensional chaotic attractor in the rheological
      parameters in terms of the expressions for the rheological parameters and the
      coupling between individually chaotically evolving orientations and the
      expressions for the rheological parameters.

PMID- 11970581
TI  - Dependence of thermal conductivity on discrete breathers in lattices.
AB  - We study the properties of heat conduction in chains of coupled particles
      subjected to different anharmonic on-site potentials. Particular emphasis is
      placed on the role of breathers in saturation of the thermal conductivity for
      chains with hard anharmonicity. When the chain particles are subject to on-site
      potentials with soft anharmonicity, we find a characteristic temperature, below
      which the conductivity decreases but while above which it increases.

PMID- 11970582
TI  - Computation of the Lyapunov spectrum for continuous-time dynamical systems and
      discrete maps.
AB  - In this paper, we describe in detail a method of computing Lyapunov exponents for
      a continuous-time dynamical system and extend the method to discrete maps. Using
      this method, a partial Lyapunov spectrum can be computed using fewer equations as
      compared to the computation of the full spectrum, there is no difficulty in
      evaluating degenerate Lyapunov spectra, the equations are straightforward to
      generalize to higher dimensions, and the minimal set of dynamical variables is
      used. Explicit proofs and other details not given in previous work are included
      here.

PMID- 11970583
TI  - Phase synchronization in the forced Lorenz system.
AB  - We demonstrate that the dynamics of phase synchronization in a chaotic system
      under weak periodic forcing depends crucially on the distribution of intrinsic
      characteristic times of this system. Under the external periodic action, the
      frequency of every unstable periodic orbit is locked to the frequency of the
      force. In systems which in the autonomous case displays nearly isochronous
      chaotic rotations, the locking ratio is the same for all periodic orbits; since a
      typical chaotic orbit wanders between the periodic ones, its phase follows the
      phase of the force. For the Lorenz attractor with its unbounded times of return
      onto a Poincare surface, such state of perfect phase synchronization is
      inaccessible. Analysis with the help of unstable periodic orbits shows that this
      state is replaced by another one, which we call "imperfect phase
      synchronization," and in which we observe alternation of temporal segments,
      corresponding to different rational values of frequency lockings.

PMID- 11970584
TI  - Escape from intermittent repellers: periodic orbit theory for crossover from
      exponential to algebraic decay.
AB  - We apply periodic orbit theory to study the asymptotic distribution of escape
      times from an intermittent map. The dynamical zeta function exhibits a branch
      point which is associated with an asymptotic power law escape. By an analytic
      continuation technique we compute a pair of complex conjugate zeroes beyond the
      branch point, associated with a preasymptotic exponential decay. The crossover
      time from an exponential to a power law is also predicted. The theoretical
      predictions are confirmed by numerical simulation. Applications to conductance
      fluctuations in quantum dots are discussed.

PMID- 11970585
TI  - Kinetic and transport equations for localized excitations in the sine-Gordon
      model.
AB  - We analyze the kinetic behavior of localized excitations--solitons, breathers,
      and phonons--in the Sine-Gordon model. Collision integrals for all types of
      localized excitation collision processes are constructed, and the kinetic
      equations are derived. We prove that the entropy production in the system of
      localized excitations takes place only in the case of inhomogeneous distribution
      of these excitations in real and phase space. We derive transport equations for
      soliton and breather densities, temperatures, and mean velocities, i.e., show
      that collisions of localized excitations lead to the creation of diffusion,
      thermoconductivity, and intrinsic friction processes. The diffusion coefficients
      for solitons and breathers, describing the diffusion processes in real and phase
      space, are calculated. It is shown that diffusion processes in real space are
      much faster than the diffusion processes in phase space.

PMID- 11970586
TI  - Continued fraction representation of temporal multiscaling in turbulence.
AB  - It was shown recently that the anomalous scaling of simultaneous correlation
      functions in turbulence is intimately related to the breaking of temporal scale
      invariance, which is equivalent to the appearance of infinitely many times scales
      in the time dependence of time-correlation functions. In this paper we derive a
      continued fraction representation of turbulent time correlation functions which
      is exact and in which the multiplicity of time scales is explicit. We demonstrate
      that this form yields precisely the same scaling laws for time derivatives and
      time integrals as the "multi-fractal" representation that was used before.
      Truncating the continued fraction representation yields the "best" estimates of
      time correlation functions if the given information is limited to the scaling
      exponents of the simultaneous correlation functions up to a certain, finite
      order. It is worth noting that the derivation of a continued fraction
      representation obtained here for a time evolution operator which is not Hermitian
      or anti-Hermitian may be of independent interest.

PMID- 11970587
TI  - Shell model for time-correlated random advection of passive scalars.
AB  - We study a minimal shell model for the advection of a passive scalar by a
      Gaussian time-correlated velocity field. The anomalous scaling properties of the
      white noise limit are studied analytically. The effect of the time correlations
      are investigated using perturbation theory around the white noise limit and
      nonperturbatively by numerical integration. The time correlation of the velocity
      field is seen to enhance the intermittency of the passive scalar.

PMID- 11970588
TI  - Structure of gaseous Kr in the low-q region by neutron scattering and interaction
      potentials.
AB  - Accurate experimental information on the long-range triplet interactions in noble
      fluids, as well as on the two-body potential, can be obtained from the low
      density behavior of the static structure factor S(q) in the small-q region. The
      results here reported of a recent low-q neutron diffraction investigation in Kr,
      devoted to undercritical densities in the range 2.4<n/nm(-3)<4.3, provide
      important indications on the pair interactions and allow also a reliable analysis
      of irreducible three-body potential effects on the measured structure, from which
      the triple-dipole Axilrod-Teller strength is extracted with unprecedented
      accuracy.

PMID- 11970589
TI  - Anomalous scaling regimes of a passive scalar advected by the synthetic velocity
      field.
AB  - The field theoretic renormalization group (RG) is applied to the problem of a
      passive scalar advected by the Gaussian self-similar velocity field with finite
      correlation time and in the presence of an imposed linear mean gradient. The
      energy spectrum in the inertial range has the form E(k) proportional to (1
      epsilon), and the correlation time at the wave number k scales as k(-2+eta). It
      is shown that, depending on the values of the exponents epsilon and eta, the
      model in the inertial-convective range exhibits various types of scaling regimes
      associated with the infrared stable fixed points of the RG equations: diffusive
      type regimes for which the advection can be treated within ordinary perturbation
      theory, and three nontrivial convection-type regimes for which the correlation
      functions exhibit anomalous scaling behavior. The explicit asymptotic expressions
      for the structure functions and other correlation functions are obtained; the
      anomalous exponents, determined by the scaling dimensions of the scalar
      gradients, are calculated to the first order in epsilon and eta in any space
      dimension. For the first nontrivial regime the anomalous exponents are the same
      as in the rapid-change version of the model; for the second they are the same as
      in the model with time-independent (frozen) velocity field. In these regimes, the
      anomalous exponents are universal in the sense that they depend only on the
      exponents entering into the velocity correlator. For the last regime the
      exponents are nonuniversal (they can depend also on the amplitudes); however, the
      nonuniversality can reveal itself only in the second order of the RG expansion. A
      brief discussion of the passive advection in the non-Gaussian velocity field
      governed by the nonlinear stochastic Navier-Stokes equation is also given.

PMID- 11970590
TI  - Capillary waves at liquid-vapor interfaces: a molecular dynamics simulation.
AB  - Evidence for capillary waves at a liquid-vapor interface are presented from
      extensive molecular dynamics simulations of a system containing up to 1.24
      million Lennard-Jones particles. Careful measurements show that the total
      interfacial width depends logarithmically on L(axially), the length of the
      simulation cell parallel to the interface, as predicted theoretically. The
      strength of the divergence of the interfacial width on L(axially) depends
      inversely on the surface tension gamma. This allows us to measure gamma two ways
      since gamma can also be obtained from the difference in the pressure parallel and
      perpendicular to the interface. These two independent measures of gamma agree
      provided that the interfacial order parameter profile is fit to an error function
      and not a hyperbolic tangent, as often assumed. We explore why these two common
      fitting functions give different results for gamma.

PMID- 11970591
TI  - Waterlike anomalies for core-softened models of fluids: one dimension.
AB  - We use a one-dimensional (1D) core-softened potential to develop a physical
      picture for some of the anomalies present in liquid water. The core-softened
      potential mimics the effect of hydrogen bonding. The interest in the 1D system
      stems from the facts that closed-form results are possible and that the
      qualitative behavior in 1D is reproduced in the liquid phase for higher
      dimensions. We discuss the relation between the shape of the potential and the
      density anomaly, and we study the entropy anomaly resulting from the density
      anomaly. We find that certain forms of the two-step square-well potential lead to
      the existence at T=0 of a low-density phase favored at low pressures and of a
      high-density phase favored at high pressures, and to the appearance of a point C'
      at a positive pressure, which is the analog of the T=0 "critical point" in the 1D
      Ising model. The existence of point C' leads to anomalous behavior of the
      isothermal compressibility K(T) and the isobaric specific heat C(P).

PMID- 11970592
TI  - Corresponding-states approach to small-angle scattering from polydisperse ionic
      colloidal fluids.
AB  - Approximate scattering functions for polydisperse ionic colloidal fluids are
      obtained by a corresponding-states approach. This assumes that all pair
      correlation functions g(alpha beta)(r) of a polydisperse fluid are conformal to
      those of an appropriate monodisperse binary fluid (reference system) and can be
      generated from them by scaling transformations. The correspondence law extends to
      ionic fluids a scaling approximation (SA) successfully proposed for nonionic
      colloids in a recent paper. For the primitive model of charged hard spheres in a
      continuum solvent, the partial structure factors of the monodisperse binary
      reference system are evaluated by solving the Orstein-Zernike (OZ) integral
      equations coupled with an approximate closure. The SA is first tested within the
      mean spherical approximation (MSA) closure, which allows analytical solutions.
      The results are found in good overall agreement with exact MSA predictions up to
      relevant polidispersity. The SA is shown to be an improvement over the
      "decoupling approximation" extended to the ionic case. The simplicity of the SA
      scheme allows its application also when the OZ equations can be solved only
      numerically. An example is then given by using the hypernetted chain closure.
      Shortcomings of the SA approach, its possible use in the analysis of experimental
      scattering data and other related points are also briefly addressed.

PMID- 11970593
TI  - Pair dispersion in synthetic fully developed turbulence.
AB  - The Lagrangian statistics of relative dispersion in fully developed turbulence is
      numerically investigated. A scaling range spanning many decades is achieved by
      generating a two-dimensional velocity field by means of a stochastic process with
      prescribed statistics and of a dynamical model (shell model) with fluctuating
      characteristic times. When the velocity field obeys Kolmogorov similarity, the
      Lagrangian statistics is self similar and agrees with Richardson's predictions
      [Proc. R. Soc. London Ser. A 110, 709 (1926)]. For intermittent velocity fields
      the scaling laws for the Lagrangian statistics are found to depend on the
      Eulerian intermittency in agreement with the multifractal description. As a
      consequence of the Kolmogorov law the Richardson law for the variance of pair
      separation is, however, not affected by intermittency corrections. Moreover,
      Lagrangian exponents do not depend on the particular Eulerian dynamics. A method
      of data analysis, based on fixed scale statistics rather than usual fixed time
      statistics, is shown to give much wider scaling range, and should be preferred
      for the analysis of experimental data.

PMID- 11970594
TI  - Percolation in ionic fluids and formation of a fractal structure.
AB  - The size of a dense region in the nonuniform distribution of particles generated
      in an ionic fluid can develop under certain conditions, as the charge on each
      particle increases. To derive this result, it is assumed that such a dense region
      is an ensemble of particles linked to each other as particle pairs that satisfy
      the condition E(ij)+u(ij)(r)< or =0, where E(ij) is the relative kinetic energy
      for i and j particles and u(ij)(r) the Coulomb potential. The percolation of the
      ensemble can be estimated analytically. The result described above has been
      derived from this estimation. According to the pair connectedness function
      derived for analytic estimation of the percolation, the dense region resulting
      from the contribution of the Coulomb attractive force between positive and
      negative particles can produce a fractal structure with a fractal dimension of
      1.5. Furthermore, a configuration of charged particles, which can be
      approximately drawn from a characteristic of the pair connectedness function,
      agrees with that of the Bjerrum theory.

PMID- 11970595
TI  - Dynamics of simulated water under pressure.
AB  - We present molecular dynamics simulations of the extended simple-point-charge
      model of water to probe the dynamic properties at temperatures from 350 K down to
      190 K and pressures from 2.5 GPa (25 kbar) down to -300 MPa (-3 kbar). We compare
      our results with those obtained experimentally, both of which show a diffusivity
      maximum as a function of pressure. We find that our simulation results are
      consistent with the predictions of the mode-coupling theory for the dynamics of
      weakly supercooled liquids--strongly supporting the hypothesis that the apparent
      divergences of dynamic properties observed experimentally may be independent of a
      possible thermodynamic singularity at low temperature. The dramatic change in
      water's dynamic and structural properties as a function of pressure allows us to
      confirm the predictions of MCT over a much broader range of the von Schweidler
      exponent values than has been studied for simple atomic liquids. We also show how
      structural changes are reflected in the wave-vector dependence of dynamic
      properties of the liquid along a path of nearly constant diffusivity. For
      temperatures below the crossover temperature of MCT (where the predictions of MCT
      are expected to fail), we find tentative evidence for a crossover of the
      temperature dependence of the diffusivity from power-law to Arrhenius behavior,
      with an activation energy typical of a strong liquid.

PMID- 11970596
TI  - Critical behavior of vorticity in two-dimensional turbulence.
AB  - We point out some similarities between the statistics of high Reynolds number
      turbulence and critical phenomena. An analogy is developed for two-dimensional
      decaying flows, in particular by studying the scaling properties of the two-point
      vorticity correlation function within a simple phenomenological framework. The
      inverse of the Reynolds number is the analog of the small parameter that
      separates the system from criticality. It is possible to introduce a set of three
      critical exponents; for the correlation length, the autocorrelation function, and
      the so-called susceptibility, respectively. The exponents corresponding to the
      well-known enstrophy cascade theory of Kraichnan and Batchelor are, remarkably,
      the same as the Gaussian approximation exponents for spin models. The limitations
      of the analogy, in particular the lack of universal scaling functions, are also
      discussed.

PMID- 11970597
TI  - Model for dynamics in supercooled water.
AB  - We propose a phenomenological model for the intermediate scattering function
      (ISF) associated with density fluctuation in low temperature water. The
      motivation is twofold: to extract various physical parameters associated with the
      ISF computed from extended simple-point-charge model water at supercooled
      temperatures, and to apply this model to analyze high resolution inelastic x-ray
      scattering data of water in the future. The ISF of the center of mass of low
      temperature water computed from 10 M-step molecular dynamics (MD) data shows
      clearly time-separated two-step relaxation with a well-defined plateau in
      between. We interpret this result as due to the formation of a stable hydrogen
      bonded, tetrahedrally coordinated cage around a typical molecule in low
      temperature water. We thus model the long-time cage relaxation by the well-known
      Kohlrausch form exp[-(t/tau)(beta)] with an amplitude factor which is a k
      dependent Debye-Waller factor A(k), and treat the short-time relaxation as due to
      molecular collisional motions within the cage. The latter motions can be
      described by the generalized Enskog equation, taking into account the confinement
      effect of the cage. We shall show that the effect of the confinement changes the
      collisional dynamics by modifying certain input parameters in the kinetic theory
      by a factor [1-A(k)](1/2). We solve the generalized Enskog equation approximately
      but analytically by a Q-dependent triple relaxation time kinetic model. This
      kinetic model was previously shown to account for the large k behavior of
      Rayleigh-Brillouin scattering from moderately dense, simple fluids. We find that
      our model fits well with the MD generated collective as well as single-particle
      ISFs. For the short-time collisional dynamics, we fix values of the hard sphere
      diameter sigma and pair correlation function at contact g(sigma), without
      introducing any adjustable parameters. The calculated ISFs reproduce the correct
      Brillouin peak frequencies at low k values. From the long-time dynamics, we
      deduce values of the Debye-Waller factor A(k), the Kohlrausch exponent beta(k),
      and the cage relaxation time tau(k).

PMID- 11970598
TI  - Slow mode of the smectic-A-smectic-C(*)(alpha) phase transition.
AB  - Unusual slow fluctuations as revealed recently by dynamic light scattering close
      to the Sm-A-Sm-C(alpha)(*) phase transition in the antiferroelectric liquid
      crystal 4-(1-methylheptyloxy-carbonyl)phenyl 4(')-octyloxy biphenyl-4-carboxylate
      can be explained by the electrostatic coupling between impurity ions and director
      fluctuations. Within the vicinity of Sm-A-Sm-C(alpha)(*) transition, the
      relaxation rate of the slow mode depends linearly on temperature, but with a
      different slope in each phase. The square root of its intensity shows a clear
      Curie-Weiss divergence at the phase transition, which is a direct confirmation of
      the electrostatic coupling mechanism.

PMID- 11970599
TI  - Structures of chiral smectic-C mesophases revealed by polarization-analyzed
      resonant x-ray scattering.
AB  - We report polarization-analyzed, resonant x-ray diffraction at the sulfur K edge
      performed upon free-standing liquid-crystal films. Our studies of the
      thiobenzoate liquid-crystal enantiomer 10OTBBB1M7 yield the polarization states
      of resonant satellite peaks arising from characteristic superlattices in the
      chiral smectic-C (SmC(*)) variant phases, including the antiferroelectric
      SmC(*)(A), ferrielectric SmC(*)(FI1) and SmC(*)(FI2), as well as SmC(*)(alpha).
      The observed polarizations agree with the clock model of chiral smectic-C
      variants, and rule out other proposals made to date for these structures. Data
      from the 10OTBBB1M7 racemate also support the clock model. Our resonant
      diffraction results from a thiophene liquid-crystal compound reveal the same
      superlattice periodicities seen in corresponding antiferroelectric and
      ferrielectric phases of 10OTBBB1M7.

PMID- 11970600
TI  - Tensorial x-ray structure factor in smectic liquid crystals.
AB  - The amplitudes and the polarizations of the different resonant reflections
      characterizing the modulation of the orientational order in smectic liquid
      crystals are derived from the molecular tensorial structure factor. In the case
      of a commensurate helicoidal modulation, our conclusions are consistent with the
      previous predictions of Dimitrienko. We have extended Dimitrienko's prediction to
      incommensurate helicoidal structures and to commensurate but nonhelicoidal
      modulations. We have compared the estimated values for different models of
      modulations with the same period, with the experimental data obtained on
      different smectic-C variants. These comparisons enable us to discriminate between
      the different models.

PMID- 11970601
TI  - Structure of the chiral smectic-C(*)(alpha) phase.
AB  - Ellipsometric measurements of freely suspended films of a chiral liquid-crystal
      compound possessing the phase sequence smectic-A-smectic-C(*)(alpha)-smectic-C*
      have been conducted in order to elucidate the structure of the smectic
      C(*)(alpha) phase. The measured ellipsometric quantities Delta and Psi are
      compared with values, which were calculated for model films using the 4x4 matrix
      method. Our results confirm, for the compound under investigation, predictions of
      a phenomenological model [M. Cepic and B. Zeks, Mol. Cryst. Liq. Cryst. 263, 61
      (1995)] according to which the smectic-C(*)(alpha) phase is characterized by a
      short-pitch helical structure.

PMID- 11970602
TI  - Microscopic origins of heliclinic phases in smectic liquid crystals.
AB  - In a previous article [Phys. Rev. E 60, 1799 (1999)], the authors considered a
      model Landau free energy that explained the ferriclinic phases of chiral smectic
      liquid crystals as a series of short period helical modulations. In this paper we
      begin with a physically more realistic, more microscopic interlayer free energy
      and show how our previous work can be derived using only simple short-ranged
      interactions. We then discuss what additional information this provides about the
      Landau coefficients used previously to construct the phase diagram for the
      heliclinic phases of chiral smectic liquid crystals. Finally, we investigate a
      means for explicitly including chirality in our model.

PMID- 11970603
TI  - Phase-ordering dynamics of the Gay-Berne nematic liquid crystal.
AB  - Phase-ordering dynamics in nematic liquid crystals has been the subject of much
      active investigation in recent years in theory, experiments, and simulations.
      With a rapid quench from the isotropic to nematic phase, a large number of
      topological defects are formed and dominate the subsequent equilibration process.
      Here we present the results of a molecular dynamics simulation of the Gay-Berne
      model of liquid crystals after such a quench in a system with 65,536 molecules.
      Twist disclination lines as well as type-1 lines and monopoles were observed.
      Evidence of dynamical scaling was found in the behavior of the spatial
      correlation function and the density of disclination lines. However, the behavior
      of the structure factor provides a more sensitive measure of scaling, and we
      observed a crossover from a defect dominated regime at small values of the wave
      vector to a thermal fluctuation dominated regime at large wave vector.

PMID- 11970604
TI  - Material-independent determination of anchoring properties on rubbed polyimide
      surfaces.
AB  - A material-independent method for determining liquid-crystal (LC) anchoring
      energy on rubbed polyimide (PI) surfaces has been devised. This method exploits
      the changes in the easy axis of rubbed PI film induced by exposure to linearly
      polarized UV (LPUV) light. The distribution of PI chains in a rubbed film is
      approximated by a Gaussian function and its width determined from the measured
      rotation of the LC easy axis as a function of exposure time. A quasimicroscopic
      free energy of the LC-substrate interface is used to model LC anchoring
      properties. The experimental and calculated values of the azimuthal anchoring
      energy are in good agreement and found to depend inversely on the width of the
      distribution function. The measurements of the width of the chain distribution
      function provide a simple LC material-independent method for determining the LC
      anchoring properties. With this method, it is also possible to calculate the
      strength of the interaction between PI chains and LC molecules.

PMID- 11970605
TI  - Surface breaking in lyotropic nematic liquid crystals induced by a magnetic
      field.
AB  - The twist deformation induced by a magnetic field H in a lyotropic liquid crystal
      is analyzed. Our results show the existence of three regimes for the surface
      deformation related to two critical values for the external magnetic field. The
      first, for low magnetic field, is an elastic one in which the surface deformation
      disappears when the field is removed. In a second regime, a permanent deformation
      of the lyotropic liquid crystal is induced by the distorting field. This regime
      is characterized by a threshold for H, called H(*)(c). In the third regime, the
      sample is uniformly oriented along H. Also this regime has a well defined
      threshold value, H(**)(c), and the alignment remains even when the distorting
      field is removed. To interpret the experimental data recently published, we
      proposed a phenomenological model according to which there is an elastic coupling
      between the surface layer of thickness l and the bulk. This elastic coupling has
      a saturation for a given value of the deformation of the bulk with respect to the
      surface layer.

PMID- 11970606
TI  - Photonic defect modes of cholesteric liquid crystals.
AB  - We investigate defect modes of cholesteric liquid crystals as photonic band gap
      materials. For normal incidence of light, cholesteric liquid crystals exhibit
      total reflection for the circular polarization with the same handedness as that
      of cholesteric helix. However, the other orthogonal component is completely
      transmitted. When we replace a thin layer of liquid crystal by an isotropic
      material as a defect, defect modes are induced for both polarizations of incident
      light. We analyze the wavelength and reflectivity of the defect modes in terms of
      the refractive index of defect layer.

PMID- 11970608
TI  - Dimensional reduction in a model with infinitely many absorbing states.
AB  - Using the Monte Carlo method, we study a two-dimensional model with infinitely
      many absorbing states. Our estimation of the critical exponent beta is
      approximately equal to 0.273(5) suggests that the model belongs to the (1+1)
      rather than to (2+1) directed-percolation universality class. We also show that
      for a large class of absorbing states the dynamic Monte Carlo method leads to
      spurious dynamical transitions.

PMID- 11970607
TI  - Molecular theory of ferroelectric ordering in enantiomeric mixtures of smectic-C*
      liquid crystals.
AB  - A molecular theory of ferroelectric ordering in smectic-C* liquid crystals
      composed of left and right enantiomers is developed taking into account the
      effects of chiral discrimination. The recently observed nonlinear dependence of
      the spontaneous polarization on the enantiomeric excess is explained in the
      framework of a molecular model that takes into consideration the strong
      electrostatic interaction between effective atomic charges in the chiral centers
      of the two enantiomers. This nonlinear dependence is determined by a difference
      of interaction energies between the pairs of chiral molecules with equal and
      opposite handedness, respectively. A relation between the molecular structure of
      different ferroelectric smectics C* and the dependence of the polarization on the
      enantiomeric excess is discussed in detail.

PMID- 11970609
TI  - Properties of the crossover from nonclassical to classical chemical kinetics in a
      reversible A+B<-->C reaction diffusion process.
AB  - We study the properties of the reaction front formed in a reversible reaction
      diffusion process A+B<-->C, with initially separated reactants. The case of the
      mobile C component is considered. In accordance with Chopard et al. [Phys. Rev. E
      47, R40 (1993)] the dynamics of the front is described as a crossover between the
      "irreversible" regime at short times and the "reversible" regime at long times. A
      refined definition for the rate of C production is suggested, taking into account
      both the forward and the backward reaction rates. By this definition within the
      framework of the mean-field equations it is shown that the reversible regime is
      characterized by scaling of the local rate of C production as R(local)
      approximately t(-1) and by scaling of the global rate of C production as
      R(global) approximately t(-1/2). It is also established that in the considered
      special case of equal diffusion coefficients and equal initial concentrations,
      the macroscopic properties of the reaction front, such as the global rate of the
      C production R(global) and the concentration profiles of the components outside
      the front reaction, are unchanged through this crossover.

PMID- 11970610
TI  - Spreading and shortest paths in systems with sparse long-range connections.
AB  - Spreading according to simple rules (e.g., of fire or diseases) and shortest-path
      distances are studied on d-dimensional systems with a small density p per site of
      long-range connections ("small-world" lattices). The volume V(t) covered by the
      spreading quantity on an infinite system is exactly calculated in all dimensions
      as a function of time t. From this, the average shortest-path distance l(r) can
      be calculated as a function of Euclidean distance r. It is found that l(r)
      approximately r for r<r(c)=[2p Gamma(d)(d-1)!](-1/d) log(2p Gamma(d)L(d)) and
      l(r) approximately r(c) for r>r(c). The characteristic length r(c), which governs
      the behavior of shortest-path lengths, diverges logarithmically with L for all
      p>0.

PMID- 11970611
TI  - Dynamical renormalization group calculation of a two-phase sharp interface model.
AB  - The temporal evolution of an interface separating two phases is studied using
      renormalization group and scaling theory and exact calculation of a sharp
      interface model incorporating surface tension and kinetic undercooling. Under
      conditions favoring rapid solidification the characteristic length, R(t), varies
      as t(1/2) while the total surface area of the interface, S(t), varies as t((d
      1)/2). This complements the results of Jasnow and Vinals who found R(t)
      approximately t in the quasistatic regime. The transition in exponents from R(t)
      approximately t to R(t) approximately t(1/2), as solidification proceeds from the
      quasistatic to the rapid solidification regime, suggests a complex evolution
      toward a self-similar late stage growth.

PMID- 11970612
TI  - Phase transition and symmetry breaking in the minority game.
AB  - We show that the minority game, a model of interacting heterogeneous agents, can
      be described as a spin system and displays a phase transition between a symmetric
      phase and a symmetry broken phase where the game's outcome is predictable. As a
      result a "spontaneous magnetization" arises in the spin formalism.

PMID- 11970613
TI  - Nonequilibrium first-order phase transition induced by additive noise.
AB  - We show that a nonequilibrium first-order phase transition can be induced by
      additive noise. As a model system to study this phenomenon, we consider a
      nonlinear lattice of overdamped oscillators with both additive and multiplicative
      noise terms. Predictions from mean field theory are successfully confirmed by
      numerical simulations. A physical explanation for the mechanism of the transition
      is given.

PMID- 11970614
TI  - Controlling Hamiltonian chaos via Gaussian curvature.
AB  - We present a method allowing one to partly stabilize some chaotic Hamiltonians
      which have two degrees of freedom. The purpose of the method is to avoid the
      regions of V(q(1),q(2)) where its Gaussian curvature becomes negative. We show
      the stabilization of the Henon-Heiles system, over a wide area, for the critical
      energy E=1/6. Total energy of the system varies only by a few percent.

PMID- 11970615
TI  - Abrupt bifurcation to chaotic scattering with discontinuous change in fractal
      dimension.
AB  - One of the major routes to chaotic scattering is through an abrupt bifurcation by
      which a nonattracting chaotic saddle is created as a system parameter changes
      through a critical value. In a previously investigated case, however, the fractal
      dimension of the set of singularities in the scattering function changes
      continuously through the bifurcation. We describe a type of abrupt bifurcation to
      chaotic scattering where this physically relevant dimension changes
      discontinuously at the bifurcation. The bifurcation is illustrated using a class
      of open Hamiltonian systems consisting of Morse potential hills.

PMID- 11970616
TI  - Rescaling invariance and anomalous transport in a stochastic layer.
AB  - The anomalous chaotic transport in a one-degree-of-freedom Hamiltonian system
      subjected to a small time-periodic perturbation is investigated. Strong
      quasiperiodic dependencies of the statistical properties of the motion on log
      epsilon are found, where epsilon is a perturbation parameter. The period log
      lambda depends on the rescaling parameter lambda, which is determined only by the
      frequency of perturbation and behavior of unperturbed Hamiltonian near a saddle
      point. The results confirm and generalize a recently established new universal
      rescaling property of perturbed motion near a saddle point.

PMID- 11970617
TI  - Density-functional theory for soft interactions by dimensional crossover.
AB  - A density-functional theory for spherical particles interacting via an arbitrary
      soft pair potential is presented. The derivation is solely based on limits, where
      the behavior is exactly known, namely, a zero-dimensional cavity and the low
      density virial expansion. The approach generalizes the fundamental-measure theory
      for hard bodies and yields the structure and thermodynamics of the homogeneous
      fluid as an output. We apply the theory to an ultrasoft logarithmic potential
      that mimics star polymers in a good solvent. The theory, when supplemented by a
      rescaling procedure, reproduces the peculiar features of the pair correlations in
      this system that we also find in computer simulations.

PMID- 11970618
TI  - Exit time of turbulent signals: a way to detect the intermediate dissipative
      range.
AB  - The exit-time statistics of experimental turbulent data is analyzed. By looking
      at the exit-time moments (inverse structure functions) it is possible to have a
      direct measurement of scaling properties of the laminar statistics. It turns out
      that the inverse structure functions show a much more extended intermediate
      dissipative range than the structure functions, leading to the first clear
      evidence of the existence of such a range of scales.

PMID- 11970619
TI  - Coherent structures in random shell models for passive scalar advection.
AB  - A study of anomalous scaling in models of passive scalar advection in terms of
      singular coherent structures is proposed. The stochastic dynamical system
      considered is a shell model reformulation of Kraichnan model. We extend the
      method introduced by Daumont, Dombre, and Gilson (e-print archive chao
      dyn/9905017) to the calculation of self-similar instantons and we show how such
      objects, being the most singular events, are appropriate to capture asymptotic
      scaling properties of the scalar field. Preliminary results concerning the
      statistical weight of fluctuations around these optimal configurations are also
      presented.

PMID- 11970620
TI  - Differential light scattering: probing the sonoluminescence collapse.
AB  - We have developed a light scattering technique based on differential measurement
      and polarization (differential light scattering, DLS) capable in principle of
      retrieving timing information with picosecond resolution without the need for
      fast electronics. DLS was applied to sonoluminescence, duplicating known results
      (sharp turnaround, self-similar collapse); the resolution was limited by
      intensity noise to about 0.5 ns. Preliminary evidence indicates a smooth
      turnaround on a less than approximately 0.5-ns time scale, and suggests the
      existence of subnanosecond features within a few nanoseconds of the turnaround.

PMID- 11970621
TI  - Liquid flow through aqueous foams: from the plateau border-dominated regime to
      the node-dominated regime.
AB  - The velocity of gravity-driven flow through aqueous foams (forced drainage) has
      been determined by using electrical conductivity measurements in foams made with
      solutions of different surfactants. There is always a scaling behavior (power
      law) between the drainage velocity V and the imposed flow rate Q: V approximately
      Q(alpha), but the alpha coefficient varies between the different surfactant
      solutions and increases with surface viscosity. An explanation of this behavior
      will be given in terms of a transition between a node-dominated and a Plateau
      border-dominated viscous dissipation, for which theory predicts respectively
      alpha=1/3 and alpha=1/2.

PMID- 11970622
TI  - Disorder effects in low concentration dispersions of small quartz spheres in
      cyanobiphenyl liquid crystals.
AB  - A photopyroelectric study of the specific heat and the thermal conductivity of
      small quartz sphere (aerosil) dispersions in heptylcyanobiphenyl (7CB) and
      octylcyanobiphenyl (8CB) liquid crystals with a concentration rho(s)=0.005 g cm(
      3) is reported. The thermal conductivity data show that, even at this low
      concentration, the elastic strain introduced in the liquid crystal by the aerosil
      particle is not completely annealed at the nematic-isotropic (NI) phase
      transition. In 8CB, annealing has been found at the smectic-nematic phase
      transition, while in the case of 7CB it occurs in the nematic phase also.
      Moreover, the depression of the NI transition temperature has been found to be
      much smaller than the one predicted by a random field model in which quenched
      disorder simply affects the average order of the sample and no effects of the
      elastic strain are considered.

PMID- 11970623
TI  - High-frequency dynamics of wave localization.
AB  - We study the effect of localization on the propagation of a pulse through a
      multimode disordered waveguide. The correlator <u(omega(1))u(*)(omega(2))> of the
      transmitted wave amplitude u at two frequencies differing by delta omega has for
      large delta omega the stretched exponential tail proportional to (- square
      root[tau(D)delta omega/2]). The time constant tau(D)=L(2)/D is given by the
      diffusion coefficient D, even if the length L of the waveguide is much greater
      than the localization length xi. Localization has the effect of multiplying the
      correlator by a frequency-independent factor exp(-L/2 xi), which disappears upon
      breaking time-reversal symmetry.

PMID- 11970624
TI  - Large two-dimensional sonic band gaps.
AB  - We show that absolute sonic band gaps produced by two-dimensional square and
      triangular lattices of rigid cylinders in air can be increased by reducing the
      structure symmetry. In the case of square lattices, symmetry reduction is
      achieved by a smaller diameter cylinder placed at the center of each unit cell.
      For triangular lattices the reduction is achieved by decreasing the diameter of
      the cylinder at the center of the hexagons in the lattice. Theoretical
      predictions are also demonstrated experimentally: starting from a honeycomb
      lattice (using cylinders of 4 cm of diameter size and 6.35 cm nearest-neighbor
      distance) we have studied the transition to a triangular symmetry by putting rods
      with increasing diameter (in the range 0.6-4 cm) at the center. The greatest
      enhancement of the attenuation strength observed in transmission experiments has
      been obtained in the high frequency region for diameter ratios in the range 0.1
      0.3.

PMID- 11970625
TI  - Tetrahedral global minimum for the 98-atom Lennard-Jones cluster.
AB  - An unusual atomic cluster structure corresponding to the global minimum of the 98
      atom Lennard-Jones cluster has been found using a variant of the basin-hopping
      global optimization algorithm. The structure has tetrahedral symmetry and an
      energy of -543.665 361 epsilon, which is 0.022 404 epsilon lower than the
      previous lowest-energy minimum. The LJ(98) structure is of particular interest
      because its tetrahedral symmetry establishes it as one of only three types of
      exception to the general pattern of icosahedral structural motifs for optimal LJ
      microclusters. Similar to the other exceptions the global minimum is difficult to
      find because it is at the bottom of a narrow funnel that only becomes
      thermodynamically most stable at low temperature.

PMID- 11970626
TI  - Eutectic colony formation: a stability analysis.
AB  - Experiments have widely shown that a steady-state lamellar eutectic
      solidification front is destabilized on a scale much larger than the lamellar
      spacing by the rejection of a dilute ternary impurity and forms two-phase cells
      commonly referred to as "eutectic colonies." We extend the stability analysis of
      Datye and Langer [V. Datye and J. S. Langer, Phys. Rev. B 24, 4155 (1981)] for a
      binary eutectic to include the effect of a ternary impurity. We find that the
      expressions for the critical onset velocity and morphological instability
      wavelength are analogous to those for the classic Mullins-Sekerka instability of
      a monophase planar interface, albeit with an effective surface tension that
      depends on the geometry of the lamellar interface and, nontrivially, on
      interlamellar diffusion. A qualitatively new aspect of this instability is the
      occurrence of oscillatory modes due to the interplay between the destabilizing
      effect of the ternary impurity and the dynamical feedback of the local change in
      lamellar spacing on the front motion. In a transient regime, these modes lead to
      the formation of large scale oscillatory microstructures for which there is
      recent experimental evidence in a transparent organic system. Moreover, it is
      shown that the eutectic front dynamics on a scale larger than the lamellar
      spacing can be formulated as an effective monophase interface free boundary
      problem with a modified Gibbs-Thomson condition that is coupled to a slow
      evolution equation for the lamellar spacing. This formulation provides additional
      physical insights into the nature of the instability and a simple means to
      calculate an approximate stability spectrum. Finally, we investigate the
      influence of the ternary impurity on a short wavelength oscillatory instability
      that is already present at off-eutectic compositions in binary eutectics.

PMID- 11970627
TI  - Rigidity phase transition in granular packings.
AB  - We numerically model two-dimensional systems of granular aggregates confined
      between two rough walls and demonstrate that at a critical grain volume fraction
      nu(c) an abrupt rigidity transition occurs. The transition has first-order
      characteristics, although the elastic constants undergo a second-order
      transition. Densely packed grains, with a volume fraction nu>nu(c), display an
      elastic-plastic rheology. Loose packings, with nu<nu(c), display gas-like
      characteristics. It is shown that when the volume fraction is allowed to change
      freely (applying a constant normal stress to the walls), it evolves spontaneously
      to nu(c) under a wide range of boundary stress values, demonstrating that the
      phase boundary is an attractive critical state.

PMID- 11970628
TI  - Influence of charge fluctuations on the critical behavior of electrolyte
      solutions.
AB  - The effective Hamiltonian of electrolyte solution near its critical point is
      constructed. The vapor-liquid critical point is investigated in detail. The
      strong dependence of the Landau-Ginsburg number on the concentration of
      electrolyte is demonstrated. It is shown that the charge fluctuations in
      electrolytes essentially suppress the fluctuation of the order parameter and
      broaden the region of classical behavior.

PMID- 11970629
TI  - Compression of a polymer chain by a small obstacle: the effect of fluctuations on
      the escape transition.
AB  - We describe the escape transition of an ideal chain compressed between finite
      sized obstacles. Three different theoretical methods are used and each provides a
      similar description of the escape transition, as predicted by earlier and less
      detailed mean-field theories. The first two methods show that thermal
      fluctuations near the transition can blur what was previously described as a
      sharp transition. The last method is an exact calculation of the partition
      function that shows unambiguously the character of the escape transition. This
      exact calculation overcomes the inherent uncertainties associated with previous
      theory and computer simulation.

PMID- 11970630
TI  - Wetting films on chemically heterogeneous substrates.
AB  - Based on a microscopic density functional theory, we investigate the morphology
      of thin liquid-like wetting films adsorbed on substrates endowed with well
      defined chemical heterogeneities. As paradigmatic cases we focus on a single
      chemical step and on a single stripe. In view of applications in microfluidics,
      the accuracy of guiding liquids by chemical microchannels is discussed. Finally
      we give a general prescription of how to investigate theoretically the wetting
      properties of substrates with arbitrary chemical structures.

PMID- 11970631
TI  - Self-motion in glass-forming polymers: a molecular dynamics study.
AB  - We present results of molecular dynamics simulations of an undercooled polymer
      melt, performed to study the validity of mode-coupling theory (MCT) for realistic
      polymer melts in general. The mean square displacements of the chain segments are
      computed to study the diffusion constant of the Rouse-like motion. It is shown
      that this diffusion constant follows a power law behavior as a function of the
      temperature, as predicted by the MCT. In addition, we studied the incoherent part
      of the intermediate scattering function and show that these functions obey the
      second scaling law of the MCT. We also calculated the relaxation times of the
      alpha-relaxation and found that they follow the same power law (gamma=2.9) as the
      diffusion constant. Using gamma, and the relationships given by MCT, we obtain
      values for a (0.27) and b (0.46) and use these exponents to describe the beta
      relaxation regime. We find that the long time part of the beta-relaxation can be
      described accurately by the Von Schweidler relaxation over a wide range of wave
      numbers. In the short time regime of the beta-relaxation, no critical decay is
      observed.

PMID- 11970632
TI  - Coupling between a first-order gas-liquid phase transition and a second-order
      orientational transition in Langmuir monolayers.
AB  - The Ginzburg-Landau theory is developed to investigate coupling between a gas
      liquid first-order phase transition (FOPT) and an orientational second-order
      phase transition (SOPT) in Langmuir monolayers. It is found that the coupled SOPT
      and FOPT takes place simultaneously if the uncoupled FOPT occurs prior to the
      SOPT with compression, and that in the opposite case, the coupling makes the FOPT
      take place at a lower pressure, but still behind the SOPT. Gas-liquid phase
      separation always leads to a decrease in the averaged order parameter of the
      orientational phase transition, which is qualitatively consistent with
      experimental data.

PMID- 11970633
TI  - Transient rheology of a polyethylene melt under shear.
AB  - Using nonequilibrium molecular dynamics simulation, we have studied the response
      of a C100 model polymer melt to a step change from equilibrium to a constant,
      high shear rate flow. The transient shear stress of the model polymer melt
      exhibits pronounced overshoot at the strain value predicted by the reptation
      model, in striking similarity to melts of longer, entangled polymer governed by
      reptation motion. At the maximum of shear stress overshoot, the molecular
      orientational order and the alignment angle are found to be midway between those
      characteristic of Newtonian flow and full alignment with the flow. The Doi
      Edwards theory is found to be applicable but only by taking into account the
      shear-rate-dependence of the terminal relaxation time. We further analyze the
      molecular origins of such behavior in short polymer chains by decomposing the
      total stress into the contributions from various molecular interactions.

PMID- 11970634
TI  - Theory of creeping gravity currents of a non-Newtonian liquid.
AB  - Recently several experiments on creeping gravity currents have been performed,
      using highly viscous silicone oils and putties. The interpretation of the
      experiments relies on the available theoretical results that were obtained by
      means of the lubrication approximation with the assumption of a Newtonian
      rheology. Since very viscous fluids are usually non-Newtonian, an extension of
      the theory to include non-Newtonian effects is needed. We derive the governing
      equations for unidirectional and axisymmetric creeping gravity currents of a non
      Newtonian liquid with a power-law rheology, generalizing the usual lubrication
      approximation. The equations differ from those for Newtonian liquids, being
      nonlinear in the spatial derivative of the thickness of the current. Similarity
      solutions for currents whose volume varies as a power of time are obtained. For
      the spread of a constant volume of liquid, analytic solutions are found that are
      in good agreement with experiment. We also derive solutions of the waiting-time
      type, as well as those describing steady flows from a constant source to a sink.
      General traveling-wave solutions are given, and analytic formulas for a simple
      case are derived. A phase plane formalism that allows the systematic derivation
      of self-similar solutions is introduced. The application of the Boltzmann
      transform is briefly discussed. All the self-similar solutions obtained here have
      their counterparts in Newtonian flows, as should be expected because the power
      law rheology involves a single-dimensional parameter as the Newtonian
      constitutive relation. Thus one finds similarity solutions whenever the analogous
      Newtonian problem is self-similar, but now the spreading relations are rheology
      dependent. In most cases this dependence is weak but leads to significant
      differences easily detected in experiments. The present results may also be of
      interest for geophysics since the lithosphere deforms according to an average
      power-law rheology.

PMID- 11970635
TI  - Two-dimensional model of phase segregation in liquid binary mixtures.
AB  - The hydrodynamic effects on the late stage kinetics of phase separation in liquid
      mixtures is studied using the model H. Mass and momentum transport are coupled
      via a nonequilibrium body force, which is proportional to the Peclet number
      alpha, i.e., the ratio between convective and diffusive molar fluxes. Numerical
      simulations based on this theoretical model show that phase separation in low
      viscosity, liquid binary mixtures is mostly driven by convection, thereby
      explaining the experimental findings that the process is fast, with the typical
      size of single-phase domains increasing linearly with time. However, as soon as
      sharp interfaces form, the linear growth regime reaches an end, and the process
      appears to be driven by diffusion, although the condition of local equilibrium is
      not reached. During this stage, the typical size of the nucleating drops
      increases like t(n), where 1/3< n <1/2, depending on the value of the Peclet
      number. As the Peclet number increases, the transition between convection- and
      diffusion-driven regimes occurs at larger times, and therefore for larger sizes
      of the nucleating drops.

PMID- 11970636
TI  - Rate-and-state theory of plastic deformation near a circular hole.
AB  - We show that a simple rate-and-state theory accounts for most features of both
      time-independent and time-dependent plasticity in a spatially inhomogeneous
      situation, specifically, a circular hole in a large stressed plate. Those
      features include linear viscoelastic flow at small applied stresses, strain
      hardening at larger stresses, and a dynamic transition to viscoplasticity at a
      yield stress. In the static limit, this theory predicts the existence of a
      plastic zone near the hole for some but not all ranges of parameters. The rate
      and-state theory also predicts dynamic failure modes that we believe may be
      relevant to fracture mechanics.

PMID- 11970637
TI  - Polyelectrolyte brushes: counterion distribution and complexation properties.
AB  - The structure of dense grafted polyelectrolyte layers has been studied with a
      combination of neutron reflectivity and infrared spectroscopy techniques. The
      polyelectrolyte brushes were made of poly(styrene sulfonate) neutralized by
      different counterions. Small counterions are distributed throughout the brush in
      order to ensure a highly local electroneutrality. In addition, they can be
      readily exchanged with other small ions. On the other hand, macromolecular
      counterions (as well as some proteins) are irreversibly trapped by the brush, but
      are located outside the grafted layer and cannot reach the surface.

PMID- 11970638
TI  - Mechanical and structural model of fractal networks of fat crystals at low
      deformations.
AB  - Fat-crystal networks demonstrate viscoelastic behavior at very small
      deformations. A structural model of these networks is described and supported by
      polarized light and atomic-force microscopy. A mechanical model is described
      which allows the shear elastic modulus (G') of the system to be correlated with
      forces acting within the network. The fractal arrangement of the network at
      certain length scales is taken into consideration. It is assumed that the forces
      acting are due to van der Waals forces. The final expression for G' is related to
      the volume fraction of solid fat (Phi) via the mass fractal dimension (D) of the
      network, which agrees with the experimental verification of the scaling behavior
      of fat-crystal networks [S. S. Narine and A. G. Marangoni, Phys. Rev. E 59, 1908
      (1999)]. G' was also found to be inversely proportional to the diameter of the
      primary particles (sigma approximately equal to 6 microm) within the network
      (microstructural elements) as well as to the diameter of the microstructures (xi
      approximately equal to 100 microm) and inversely proportional to the cube of the
      intermicrostructural element distance (d(0)). This formulation of the elastic
      modulus agrees well with experimental observations.

PMID- 11970639
TI  - Dissipation in ferrofluids: mesoscopic versus hydrodynamic theory.
AB  - Part of the field dependent dissipation in ferrofluids occurs due to the
      rotational motion of the ferromagnetic grains relative to the viscous flow of the
      carrier fluid. The classical theoretical description due to Shliomis (Zh. Eksp.
      Teor. Fiz. 61, 2411 (1971) [Sov. Phy JETP 34, 1291 (1972)]) uses a mesoscopic
      treatment of the particle motion to derive a relaxation equation for the
      nonequilibrium part of the magnetization. Complementary, the hydrodynamic
      approach of Liu [Phys. Rev. Lett. 70, 3580 (1993)] involves only macroscopic
      quantities and results in dissipative Maxwell equations for the magnetic fields
      in the ferrofluid. Different stress tensors and constitutive equations lead to
      deviating theoretical predictions in those situations, where the magnetic
      relaxation processes cannot be considered instantaneous on the hydrodynamic time
      scale. We quantify these differences for two situations of experimental
      relevance, namely, a resting fluid in an oscillating oblique field and the
      damping of parametrically excited surface waves. The possibilities of an
      experimental differentiation between the two theoretical approaches is discussed.

PMID- 11970640
TI  - Different statistical mechanical ensembles for a stretched polymer.
AB  - Imposing to a single polymer chain of N monomers either a fixed pair of forces +/
      f acting at the chain ends (stress ensemble) or a fixed end-to-end vector R
      (strain ensemble) does correspond to the use of different statistical mechanical
      ensembles. In particular, the two elasticity laws, R(f)=g(f) and f(R)=h(R), where
      R(f) is the length of the average end-to-end vector <R>(f) in the stress ensemble
      and f(R) is the intensity of the average internal force <f>(R) in the strain
      ensemble, are not equivalent. For these conjugated ensembles, the quantity
      Delta(f)=f-h(g(f)) and more generally Delta(O)=<O>(f)-<O>(R) where O is an
      arbitrary observable, is studied systematically in this paper for a wide class of
      polymer models corresponding to chains at temperatures equal or above the theta
      point. The leading term Delta((2))(O) of an expansion of Delta(O) in terms of the
      successive moments of the end-to-end vector fluctuations in the stress ensemble
      can be used to analyze the scaling properties of Delta(f). For the Gaussian and
      the freely jointed chain models, Delta(O) proportional to 1/N for large N with
      the particularity that, for the elasticity law, Delta(f) strictly vanishes for
      the Gaussian chain at any finite N. For chains in good solvent, the usual result
      Delta(f) proportional to 1/N at fixed f is only valid in the highly stretched
      chain regime (Pincus regime). N independent large ensemble differences of the
      order of 20% on Delta(f) are noticed when the chain is stretched over a distance
      of the order of the unstretched chain average end-to-end distance R0. These
      effects decrease to the 1% level for R(f)>3R(0). Monte Carlo calculations for a
      chain model containing both excluded volume and finite extensibility features
      illustrate the distinction between the elasticity laws in the two ensembles over
      all stretching regimes. Our study suggests that the nature of the constraints
      used in single chain micromanipulations could be relevant to the interpretation
      of experimental elasticity law data.

PMID- 11970641
TI  - Transitions in the horizontal transport of vertically vibrated granular layers.
AB  - Motivated by recent advances in the investigation of fluctuation-driven ratchets
      and flows in excited granular media, we have carried out experimental and
      simulational studies to explore the horizontal transport of granular particles in
      a vertically vibrated system whose base has a sawtooth-shaped profile. The
      resulting material flow exhibits novel collective behavior, both as a function of
      the number of layers of particles and the driving frequency; in particular, under
      certain conditions, increasing the layer thickness leads to a reversal of the
      current, while the onset of transport as a function of frequency occurs gradually
      in a manner reminiscent of a phase transition. Our experimental findings are
      interpreted here with the help of extensive, event driven Molecular Dynamics
      simulations. In addition to reproducing the experimental results, the simulations
      revealed that the current may be reversed as a function of the driving frequency
      as well. We also give details about the simulations so that similar numerical
      studies can be carried out in a more straightforward manner in the future.

PMID- 11970642
TI  - Negative electrostatic contribution to the bending rigidity of charged membranes
      and polyelectrolytes screened by multivalent counterions.
AB  - Bending rigidity of a charged membrane or polyelectrolyte screened by monovalent
      counterions is known to be enhanced by electrostatic effects. We show that in the
      case of screening by multivalent counterions the electrostatic effects reduce the
      bending rigidity. This inversion of the sign of the electrostatic contribution is
      related to the formation of two-dimensional strongly correlated liquids (SCL) of
      counterions at the charged surface due to strong lateral repulsion between them.
      When a membrane or a polyelectrolyte is bent, SCL is compressed on one side and
      stretched on the other so that thermodynamic properties of SCL contribute to the
      bending rigidity. Thermodynamic properties of SCL are similar to those of Wigner
      crystal and are anomalous in the sense that the pressure, compressibility and
      screening radius of SCL are negative. This brings about substantial negative
      correction to the bending rigidity. For the case of DNA this effect qualitatively
      agrees with experiment.

PMID- 11970643
TI  - Exact Poisson-Boltzmann solution for the interaction of dissimilar charge
      regulating surfaces.
AB  - An efficient method is proposed to calculate the electric double layer force
      between two flat surfaces of dissimilar composition and ionization properties.
      The approach is based on explicit expressions for the solution of the (nonlinear)
      Poisson-Boltzmann equation and allows for boundary conditions of charge
      regulation, i.e., chemical equilibrium of both surfaces with a bulk electrolyte
      at all surface separations. As an illustration, we discuss in some detail the
      interaction between a weakly acidic and a strongly acidic latex surface, and
      between an acidic (silica) surface and an amphoteric (rutile) surface.

PMID- 11970644
TI  - Application of liquid dynamics theory to the glass transition.
AB  - In monatomic liquid dynamics theory, the system moves among a large number of
      intersecting nearly harmonic valleys in the many-particle potential energy
      surface. The same potential surface underlies the motion of atoms in the
      supercooled liquid. As temperature is decreased below the melting temperature,
      the motion among the potential valleys will begin to freeze out, and the system
      will pass out of equilibrium. It is therefore necessary to develop a
      nonequilibrium theory, based on the Hamiltonian motion. The motion is separated
      into two distinct parts, and idealized as follows: (a) the vibrational motion
      within a single valley is assumed to be purely harmonic, and remaining in
      equilibrium; and (b) the transit motion, which carries the system from one valley
      to another, is assumed to be instantaneous, and energy and momentum conserving.
      This idealized system is capable of exhibiting a glass transition behavior. An
      elementary model, incorporating the idealized motion, is the independent atom
      model, originally developed to treat self diffusion in monatomic liquids. For
      supercooled liquids, in the independent atom model, the vanishing of self
      diffusion at a finite temperature implies the same property for the transit
      probability. The vanishing of the transit probability at a finite temperature
      supports the view that transits are not merely thermally activated, but are
      controlled by phase-space correlations. For supercooled liquid sodium, the
      transit probability has Vogel-Tamann-Fulcher temperature dependence. The
      independent atom model is shown to be capable of exhibiting all the essential
      glass transition properties, including rate dependence of the glass transition
      temperature, and both exponential and nonexponential relaxation.

PMID- 11970645
TI  - Interfacial free energy of hard-sphere fluids and solids near a hard wall.
AB  - A hard-sphere system near a planar structureless hard wall is considered in
      thermodynamic equilibrium. The associated interfacial free energies are
      calculated both for a bulk fluid and a bulk face-centered-cubic crystal along
      (111), (110), and (100) orientation. Combining Monte Carlo simulations and
      thermodynamic integration, we obtain the wall-fluid and the wall-solid
      interfacial free energy over the whole range of possible bulk densities. The
      "exact" computer simulation data are compared to theoretical approximations. For
      moderate bulk densities, the wall-fluid interfacial free energies compare
      reasonably well with scaled-particle theory and density functional results. For
      the wall-crystal interface, we propose a simple analytical cell theory which
      yields good agreement with our simulation data over the whole range of bulk
      crystal densities.

PMID- 11970646
TI  - Self-diffusion of grains in a two-dimensional vibrofluidized bed.
AB  - The analogy of vibrofluidized granular beds with a thermal gas of hard discs has
      been tested. Analysis of the mean squared displacement behavior of the grains
      allowed comparison of the measured diffusion with the predicted value at a
      particular combination of granular temperature and packing fraction. High speed
      photography, image analysis, and particle tracking software enabled accurate
      location of the grains. Appropriate analysis of the three mean squared
      displacement regimes, ballistic, diffusive, and crossover between the two
      extremes, allowed both the diffusion coefficient and the granular temperature to
      be measured at the same packing fraction. Broad agreement between Chapman-Enskog
      theory relating temperature to self-diffusion and observation was observed up to
      packing fractions of eta approximately equal to 0.7. At higher packing fractions
      the grains showed evidence of caging and jump diffusion, with the observed
      diffusion rapidly diverging from that predicted by theory. Measurement of self
      diffusion coefficients and subsequent use of kinetic theory was found to be an
      accurate method to determine the granular temperature for intermediate packing
      fractions (eta=0.4-0.6), and would be particularly suitable for those situations
      where the time resolution of the experimental facility is insufficient to resolve
      the speed of the grain between collisions.

PMID- 11970647
TI  - Interaction and percolation in the L64 triblock copolymer micellar system.
AB  - We present results of analyses of an extensive set of static light scattering
      (SLS), small angle neutron scattering (SANS), and viscoelastic (frequency
      dependent complex moduli) measurements of aqueous solutions of a triblock
      copolymer micellar system. We investigate Pluronic L64 (PEO(13)PPO(30)PEO(13))
      water system in a wide range of composition and temperature. We determine phase
      diagram of the disordered micellar phase, including a cmc-cmt curve, a cloud
      point curve, the critical concentration, and the critical temperature by means of
      SLS and SANS. The microstructure and interaction between micelles are determined
      by analyses of SANS intensities. SANS intensity distributions are well described
      by combining the cap-and-gown model for the polymer segmental distribution within
      a micelle and the sticky hard sphere model for the intermicellar structure
      factor. The existence of percolation loci at well defined poins in the
      temperature-concentration plane is inferred from an abrupt increase of the
      stickiness parameter extracted from SANS data and from two order of magnitude
      jump of the complex moduli at the percolation point. Study of temperature
      dependence of real (storage) and imaginary (loss) part of the complex modulus at
      fixed concentration and frequency lends further support to the existence of a
      percolation line. We observe an increase of some order of magnitude of the real
      and imaginary part of viscosity at certain temperature and composition, a
      phenomenon usually ascribed to a gelation process in a polymer solution. The
      definitive confirmation of the percolation process is obtained by frequency
      dependent complex viscosity measured in a frequency range 0-160 (rad/sec). From
      these measurements we clearly observe a well defined frequency scaling behavior
      of the complex moduli and a loss angle (delta) independent of the frequency.
      Scaling exponents, determined for frequency-dependent complex moduli satisfy the
      scaling relations predicted by the scalar elasticity percolation theory.

PMID- 11970648
TI  - Lattice model results for lamellar phases in slits.
AB  - A mixture of oil, water, and surfactant confined between parallel hydrophilic
      walls is studied close to phase boundaries between lamellar and uniform phases
      within a vector lattice model in a mean-field approximation. Relations between
      energy and force-distance profiles, and the structure of the confined fluid
      (given by density profiles) are found and discussed. For large wall separations L
      elastic response to compression or decompression, accompanied by shrinking or
      swelling of the period lambda of the lamellar phase, is found for lamellar and
      induced (by capillary condensation) lamellar phases. Very good agreement with
      recent experiments is obtained. For L<4 lambda the system responds to
      decompression by swelling of the central, either oil- or water-rich layer, with
      the layers adsorbed at the surfaces remaining unaffected. The solvation force is
      very weak and independent of L when the central layer is swollen, and jumps to
      much larger values when new layers are introduced into the slit.

PMID- 11970649
TI  - Computer simulation of random packing of unequal particles.
AB  - A Monte Carlo simulation model for the random packing of unequal spherical
      particles is presented in this paper. With this model, the particle radii obeying
      a given distribution are generated and randomly placed within a cubic packing
      domain with high packing density and many overlaps. Then a relaxation iteration
      is applied to reduce or eliminate the overlaps, while the packing space is
      gradually expanded. The simulation is completed once the mean overlap value falls
      below a preset value. To simulate the random close packing, a "vibration" process
      is applied after the relaxation iteration. For log-normal distributed particles,
      the effect of particle size standard deviation, and for bidisperse particles, the
      effects of particle size ratio and the volume fraction of large particles on
      packing density and on coordination number are investigated. Simulation results
      show good agreement with that obtained by experiments and by other simulations.
      The randomness, homogeneity, and isotropy, which have not been evaluated before
      for packing of distributed particles, are also examined using statistical
      measures.

PMID- 11970650
TI  - Effects of confinement on critical adsorption: absence of critical depletion for
      fluids in slit pores.
AB  - The adsorption of a near-critical fluid confined in a slit pore is investigated
      by means of density functional theory and by Monte Carlo simulation for a Lennard
      Jones fluid. Our work was stimulated by recent experiments for SF6 adsorbed in a
      mesoporous glass, which showed the striking phenomenon of critical depletion,
      i.e., the adsorption excess Gamma first increases but then decreases very rapidly
      to negative values as the bulk critical temperature T(c) is approached from above
      along near-critical isochores. By contrast, our density functional and simulation
      results, for a range of strongly attractive wall-fluid potentials, show Gamma
      monotonically increasing and eventually saturating as the temperature is lowered
      toward T(c) along both the critical (rho=rho(c)) and subcritical isochores
      (rho<rho(c)). Such behavior results from the increasingly slow decay of the
      density profile away from the walls, into the middle of the slit, as T-->T(+)(c).
      For rho<rho(c) we find that in the fluid the effective bulk field, which is
      negative and which favors desorption, is insufficient to dominate the effects of
      the surface fields which favor adsorption. We compare this situation with earlier
      results for the lattice gas model with a constant (negative) bulk field where
      critical depletion was found. A qualitatively different behavior of the density
      profiles and adsorption is found in simulations for intermediate and weakly
      attractive wall-fluid potentials, but in no case do we observe the critical
      depletion found in experiments. We conclude that the latter cannot be accounted
      for by a single pore model.

PMID- 11970651
TI  - Pattern formation in the instability of a vicinal surface by the drift of
      adatoms.
AB  - We study the behavior of steps in a vicinal face with drift of adsorbed atoms
      (adatoms) by an external field. When the drift is in the downhill direction and
      its velocity exceeds critical values, v(x)(c) and v(y)(c), the vicinal face is
      linearly unstable to long-wavelength fluctuations parallel and/or perpendicular
      to the steps. By taking the continuum limit of the step-flow model, we derive an
      anisotropic Kuramoto-Sivashinsky equation with propagative terms, which describes
      the motion of an unstable vicinal face. Its numerical solution shows ripples or a
      zigzag pattern expected from the linear analysis. Nonlinearity becomes important
      in the late stage and, depending on the condition, various patterns are formed:
      regular step bunches, a hill and valley structure tilted from the initial step
      direction, mounds, and a chaotic pattern.

PMID- 11970652
TI  - Dynamics of a shallow fluidized bed.
AB  - The results of the experimental study of the dynamics of a shallow fluidized bed
      are reported. The behavior of granular material is controlled by the interplay of
      two factors--levitation due to the upward airflow, and sliding back due to
      gravity. Near the threshold of instability, the system shows critical behavior
      with remarkably long transient dynamics. The experimental observations are
      compared with a simple cellular automata model.

PMID- 11970653
TI  - Single-particle dynamics of water molecules confined in a lecithin-based gel.
AB  - We present experimental measurements, obtained by a quasielastic neutron
      scattering experiment, of the self-diffusion coefficient of water confined in the
      dense structure of lecithin-based gels. The inelastic neutron scattering (INS)
      technique was also used to monitor the dynamic state of water molecules involved
      in the gel structure. It is shown that, at least in highly concentrated systems,
      the diffusional properties of water can be related with the growth process of
      worm-like aggregates. However, an interpretation of our data consistent with a
      number of experimental results in the literature and with INS indications
      requires the adoption of a model in which the gel structure is better described
      in terms of percolating aggregates rather than the usually described polymer-like
      entangled (not interconnected) network. In such a way, we are pointing out the
      existence of an interpretative controversy calling for further investigation to
      be disentangled. The source of the inconsistencies is found in the commonly
      accepted basic assumption of the existence of a simple scaling law, relating the
      average micellar length to the concentration.

PMID- 11970654
TI  - Granular collapse as a percolation transition.
AB  - Inelastic collapse is found in a two-dimensional system of inelastic hard disks
      confined between two walls which act as an energy source. As the coefficient of
      restitution is lowered, there is a transition between a state containing small
      collapsed clusters and a state dominated by a large collapsed cluster. The
      transition is analogous to that of a percolation transition. At the transition
      the number of clusters n(s) of size s scales as n(s) approximately s(-tau) with
      tau approximately equal to 2.7.

PMID- 11970655
TI  - Size distribution effect on the power law regime of the structure factor of
      fractal aggregates.
AB  - We consider the large qR(g), where q is the magnitude of the scattering wave
      vector and R(g) is the aggregate radius of gyration, part of the structure factor
      of fractal aggregates, and quantify the coefficient C of the power law, S(q)
      approximately C(qR(g))(-D), where D is the fractal dimension, for various
      structure factors proposed in the literature. With the aid of earlier work, we
      conclude the most accurate structure factors have C=1.0. We then calculate the
      effects of polydispersity on this coefficient, and show the effects are
      significant, enough so to allow a measurement of the distribution width. These
      concepts are accurately supported with scattering data from a diffusion limited
      aerosol and a reaction limited colloid.

PMID- 11970656
TI  - Stress fluctuations in continuously sheared dense granular materials.
AB  - At high solid concentrations, computer simulations of sheared granular materials
      comprised of randomly arranged, monodisperse, smooth, inelastic spherical
      particles flowing in a Couette geometry show large fluctuations in the normal
      stress at the walls. These fluctuations are characterized by a marked asymmetric
      amplitude distribution similar to those observed in recent experiments. In these
      systems the particles' mean square displacement in the shear direction is
      observed to vanish locally which indicates the formation of crystallized regions.
      However, there are other regions in the system with nonzero values for the mean
      square displacement in the shear direction. This observation indicates that a
      sheared monodisperse granular material initially in a disordered state could
      evolve to a system in which the crystal phase is formed largely with a well
      defined interface between different phases. The periodic phase transition is
      observed between the compressed, highly ordered crystalline state and the
      dilated, less ordered state of the layer of particles adjacent to the wall, which
      may explain the stick-slip behavior which occurred in the experiments.

PMID- 11970657
TI  - Crystallization in quasi-two-dimensional colloidal systems at an air-water
      interface.
AB  - The crystallization of colloidal particles at an air-water interface is
      investigated by computer simulations. We numerically clarify the bond
      orientational order parameter Phi(6) with different particle concentrations. In
      addition, the profiles of the pair-correlation function g(r), the orientational
      correlation function g(B)(r), and the static structure factor S(q) of this system
      are calculated. We find the two-stage melting of the colloidal crystal and the
      existence of the hexatic phase at intermediate concentration.

PMID- 11970658
TI  - Negative effective surface viscosities in insoluble fatty acid monolayers: effect
      of phase transitions on dilational viscoelasticity.
AB  - The viscoelastic properties of insoluble monolayers have been investigated by the
      excited electrocapillary waves method. Effective negative values of dilational
      viscosities have been obtained in the liquid expanded and liquid condensed phases
      of insoluble monolayers of myristic, pentadecanoic, and stearic acids. However,
      the surface viscosity remains positive for the more expanded monolayers of ethyl
      palmitate ester. Possible origins of such a behavior are discussed in terms of
      transitional effects between the two-dimensional coexisting phases.

PMID- 11970659
TI  - Brownian motion in a granular gas.
AB  - The dynamics of a heavy particle in a gas of much lighter particles is studied
      via the Boltzmann-Lorentz equation with inelastic collisions among all particles.
      A formal expansion in the ratio of gas to tagged particle mass transforms the
      Boltzmann-Lorentz equation into a Fokker Planck equation. The predictions of the
      latter are tested here using direct Monte Carlo simulation of the Boltzmann
      Lorentz equation. Excellent agreement is obtained for the approach to a
      homogeneous cooling state, the temperature of that state, approach to diffusion,
      and the dependence of the diffusion constant on dissipation parameters. Some
      results from molecular-dynamics simulations are also presented and shown to agree
      with the theoretical predictions.

PMID- 11970660
TI  - Shell structures with "magic numbers" of spheres in a swirled dish.
AB  - Molecular dynamic simulations of a low number N< or = 54 of spheres in a swirled
      dish yield solid-like shell structures with stable rings. In contrast to known
      granular media, solidification occurs only at singular values of N: 7, 8, 12, 14,
      19, 21, 30, 37, 40. Otherwise, we obtain intermittent switching of particles
      between rings -- the average switching time scaling exponentially with a control
      parameter -- or fluid-like disorder. Stable shell structures can be classified by
      particular geometrical arrangements (one-centered hexagonal, one-centered
      "quasicircular," three centered, and four centered).

PMID- 11970661
TI  - Phase-field model for binary alloys.
AB  - We present a phase-field model (PFM) for solidification in binary alloys, which
      is found from the phase-field model for a pure material by direct comparison of
      the variables for a pure material solidification and alloy solidification. The
      model appears to be equivalent with the Wheeler-Boettinger-McFadden (WBM) model
      [A.A. Wheeler, W. J. Boettinger, and G. B. McFadden, Phys. Rev. A 45, 7424
      (1992)], but has a different definition of the free energy density for
      interfacial region. An extra potential originated from the free energy density
      definition in the WBM model disappears in this model. At a dilute solution limit,
      the model is reduced to the Tiaden et al. model [Physica D 115, 73 (1998)] for a
      binary alloy. A relationship between the phase-field mobility and the interface
      kinetics coefficient is derived at a thin-interface limit condition under an
      assumption of negligible diffusivity in the solid phase. For a dilute alloy, a
      steady-state solution of the concentration profile across the diffuse interface
      is obtained as a function of the interface velocity and the resultant partition
      coefficient is compared with the previous solute trapping model. For one
      dimensional steady-state solidification, where the classical sharp-interface
      model is exactly soluble, we perform numerical simulations of the phase-field
      model: At low interface velocity, the simulated results from the thin-interface
      PFM are in excellent agreement with the exact solutions. As the partition
      coefficient becomes close to unit at high interface velocities, whereas, the
      sharp-interface PFM yields the correct answer.

PMID- 11970662
TI  - Phase transitions of colloid-polymer systems in two dimensions.
AB  - Phase transitions of systems consisting of colloidal particles and non-adsorbing
      polymer in a solvent are studied theoretically in two dimensions. The colloids
      are modeled as hard spheres and the polymer as an ideal gas. The imbalance in
      osmotic pressure induced by the depletion effect gives rise to an effective
      attraction tail for the colloid-colloid interaction. For a monodisperse polymer,
      liquid-liquid separation is predicted to occur for appropriate colloid
      concentrations when the ratio s of the radius of gyration of the polymer to the
      radius of the colloidal particle is greater than 0.31, while solid-liquid
      separation is predicted to occur for all colloid concentrations when s is smaller
      than 0.31. Polydispersity of polymer is found to increase the extent of liquid
      liquid coexistence, and when the average s is smaller than 0.31, and for
      appropriate colloid concentrations, liquid-liquid coexistence occurs provided the
      polymer size distribution is broad enough. Partitioning and size distribution of
      polymer in coexisting phases are also predicted.

PMID- 11970663
TI  - Size segregation of granular matter in silo discharges.
AB  - We present an experimental study of segregation of granular matter in a quasi-two
      dimensional silo emptying out of an orifice. Size separation is observed when
      multisized particles are used with the larger particles found in the center of
      the silo in the region of fastest flow. We use imaging to study the flow inside
      the silo and quantitatively measure the concentration profiles of bidisperse
      beads as a function of position and time. The angle of the surface is given by
      the angle of repose of the particles, and the flow occurs in a few layers only
      near the top of this inclined surface. The flowing region becomes deeper near the
      center of the silo and is confined to a parabolic region centered at the orifice
      which is approximately described by the kinematic model. The experimental
      evidence suggests that the segregation occurs on the surface and not in the flow
      deep inside the silo where velocity gradients also are present. We report the
      time development of the concentrations of the bidisperse particles as a function
      of size ratios, flow rate, and the ratio of initial mixture. The qualitative
      aspects of the observed phenomena may be explained by a void filling model of
      segregation.

PMID- 11970664
TI  - Linear stability analysis of a vertically oscillated granular layer.
AB  - We present a linear stability analysis of an oscillating granular layer, treating
      it as an isothermal incompressible fluid with zero surface tension, which
      undergoes periodic collisions with and separations from an oscillating plate.
      Because the viscosity of the granular layer is unknown, we use the experimental
      value of the critical acceleration for the transition from a flat to patterned
      layer as input for the theory, and use the analysis to calculate the granular
      viscosity and the wavelength of the most unstable mode. The wavelength compares
      favorably with the experimental pattern wavelength. Further, we find that the
      wavelengths are controlled by the viscosity of the granular layer.

PMID- 11970665
TI  - Experimental measurements of sidebranching in thermal dendrites under terrestrial
      gravity and microgravity conditions.
AB  - We perform sidebranch measurements on pure succinonitrile dendrites grown in both
      microgravity and terrestrial-gravity conditions for a set of supercoolings within
      the range 0.1-1.0 K. Two distinct types of sidebranch regions, uniform and
      coarsening, exist, and are characterized by the distance from the tip at which
      the region began, D(i), and the average spacing of sidebranches within that
      region, lambda(i). There does not appear to be any significant dependence on
      either gravity level or supercooling when D(i) or lambda(i) are normalized with
      respect to the radius of curvature of the tip, R. The apparently constant
      normalized proportionality factor between D(i), lambda(i), and R, regardless of
      the relative importance of diffusion and convective heat transport, demonstrates
      self-similarity between dendrites of different length scales propagating under
      various heat transfer conditions. However, when the form of the sidebranch
      envelope is defined by a power law relating the amplitude and relative positions
      of the sidebranches normalized to the radius of the tip, the form is seen to have
      significant variations with supercooling between the terrestrial gravity and
      microgravity growth dendrites. Furthermore, both the amplitude coefficient and
      exponent from the power-law regressions of the microgravity data are
      statistically different (95% confidence level) than their terrestrial
      counterparts.

PMID- 11970666
TI  - Competition between correlated buoyancy and uncorrelated capillary effects during
      drainage.
AB  - We study drainage in a horizontally oriented rough fracture joint filled with
      glass beads. The shape and structure of the drained areas is the result of
      competition between two effects: (1) variations in the capillary thresholds
      necessary to be overcome in order to drain the pores and (2) the height
      variations due to the roughness of the fracture joint. These height variations
      have long range correlations due to the self-affine nature of the fracture. The
      capillary thresholds are uncorrelated. We tune the relative strength of these two
      effects by performing experiments in a centrifuge and thus changing the "strength
      of gravity." As gravity is increased, the structure of the drained areas change
      from that of invasion percolation to a structure composed of compact blobs linked
      together by threadlike links. We study both the geometry and the effect of
      trapping while changing acceleration of gravity from zero to 6g(0). At high
      centrifugal acceleration we further observe fragmentation, migration and
      coalescence of bubbles of fluid inside the drained areas.

PMID- 11970667
TI  - Response of an ensemble of noisy neuron models to a single input.
AB  - Spike timing precision in response to a subthreshold stimulation can be enhanced
      by noise in ensembles of neurons [X. Pei, L. Wilkens, and F. Moss, Phys. Rev.
      Lett. 77, 4679 (1996)]. We elucidate the mechanism underlying this phenomenon by
      computing the membrane potential distributions of ensembles of Hodgkin-Huxley
      neuron models. For small noise amplitudes, the membrane potential distribution
      takes on a Gaussian form centered on the resting potential, while for large
      fluctuations, there is a significant spread to lower potentials. These two
      regimes are separated by a relatively narrow band where the distributions transit
      rapidly from the Gaussian-like shapes to the spread ones. We argue that the
      optimal noise that maximizes the spike timing precision is situated close to this
      boundary.

PMID- 11970668
TI  - Conformations of closed DNA.
AB  - We examine the conformations of a model for a short segment of closed DNA. The
      molecule is represented as a cylindrically symmetric elastic rod with a
      constraint corresponding to a specification of the linking number. We obtain
      analytic expressions leading to the spatial configuration of a family of
      solutions representing distortions that interpolate between the circular form of
      DNA and a figure-eight form that represents the onset of interwinding. We are
      also able to generate knotted loops. We suggest ways to use our approach to
      produce other configurations relevant to studies of DNA structure. The stability
      of the distorted configurations is assessed, along with the effects of
      fluctuations on the free energy of the various configurations.

PMID- 11970669
TI  - Chemically driven traveling waves in DNA.
AB  - The nonlinear mechanical model constructed in a previous paper [Nuovo Cimento D
      20, 833 (1998)] is developed in order to study the dynamics of the DNA double
      helix. It is assumed that the hydrophobic interaction between subsequent base
      pairs may be influenced by a RNA polymerase. The Lagrangian, constructed on the
      basis of "geometrical" properties of the DNA molecule, depends on time and
      contains first and second derivatives of the twist angle. The energy dissipation
      term is added to the dynamical equations resulting from the Lagrange formalism.
      It is proved that the system has pulse-like solitary wave solutions for which the
      dissipated energy is balanced by the energy pumped by the advancing RNA
      polymerase. The physical interpretation of our solution is the local untwisting
      of the DNA molecule during transcription of messenger RNA.

PMID- 11970670
TI  - Dynamics of lattice spins as a model of arrhythmia.
AB  - We consider evolution of initial disturbances in spatially extended systems with
      autonomous rhythmic activity, such as the heart. We consider the case when the
      activity is stable with respect to very smooth (changing little across the
      medium) disturbances and construct lattice models for description of not-so
      smooth disturbances, in particular, topological defects; these models are
      modifications of the diffusive XY model. We find that when the activity on each
      lattice site is very rigid in maintaining its form, the topological defects-
      vortices or spirals--nucleate a transition to a disordered, turbulent state.

PMID- 11970671
TI  - Analytical approach to the stochastic FitzHugh-Nagumo system and coherence
      resonance.
AB  - We consider the FitzHugh-Nagumo system under the influence of white Gaussian
      noise in the excitable regime. We present an analytical approximation in the
      limit of fast activator time scale. Marginal probability densities of a reduced
      system and dynamical quantities such as the pulse rate are found and the mean
      interspike interval and its relative standard deviation are investigated. The
      latter quantities allow a quantitative description of the phenomenon of coherence
      resonance, as comparisons with simulations show.

PMID- 11970672
TI  - Proteins in vacuo: a molecular dynamics study of the unfolding behavior of highly
      charged disulfide-bond-intact lysozyme subjected to a temperature pulse.
AB  - Molecular dynamics simulations were used to interpret a variety of experimental
      data on highly charged disulfide-bond-intact lysozyme in vacuo. The simulation
      approach involved submitting a model of the protein [Reimann, Velazquez, and
      Tapia, J. Phys. Chem. B 102, 9344 (1998)] in a given charge state to a 3-ns-long
      heat pulse (usually at 500 K) followed by cooling or relaxation for 1 ns back to
      room temperature (293 K). This treatment yielded a charge threshold around
      Q(0)=8+ for obtaining significant unfolding, as indicated by an enhancement in
      collision cross section and conformer length. The collision cross sections and
      lengths theoretically obtained, along with the threshold charge state for
      initiating unfolding, were compatible with experimental results on lysozyme in
      vacuo. The unfolded, highly elongated conformations obtained for Q> or = 9+
      displayed a significant level of non-native beta-sheet content which appeared to
      be additionally stabilized by charge self-solvation.

PMID- 11970673
TI  - Specular and diffuse scattering of highly aligned phospholipid membranes.
AB  - We present a quantitative study of specular and diffuse (non-specular) x-ray and
      neutron reflectivity from highly aligned phospholipid membranes deposited on
      solid substrates. The height-height correlation function could be obtained from
      the diffuse scattering without further model assumptions. The results differ
      significantly from the linear theory of smectic elasticity. We argue that the
      diffuse scattering is dominated by static liquid-crystalline defects, rather than
      thermal fluctuations.

PMID- 11970674
TI  - Simple model to study insertion of a protein into a membrane.
AB  - A simple coarse grained model on a two-dimensional lattice is presented to
      elucidate the main effects ruling the insertion of a protein into a polar
      environment such as a lipidic membrane. The amino acids are divided into two
      classes (hydrophobic or polar), and they behave differently according to their
      surroundings. In aqueous solution the hydrophobic amino acids are forced to
      minimize contacts with water, whereas in the apolar environment all the amino
      acids try to aggregate regardless to their specificity. The lattice is employed
      in order to perform exact calculations and to generate a fictitious protein data
      bank. Despite the simplicity of the model, some morphological features of the
      protein-like lattice structures obtained by our model are compatible with the
      observed phenomenology of transmembrane proteins. These results seem to
      corroborate the hypothesis that the number of classes into which the amino acids
      can be divided that correctly describe the phenomena may be extremely low.

PMID- 11970676
TI  - Independent statistical observables for ultrametric disordered populations.
AB  - It is not exceptional that a sample of N random data X(i), i=1,...,N contains
      ultrametric covariations, namely the matrix C with matrix elements <X(i)X(j)>
      <X(i)><X(j)> is ultrametric. We define independent (decorrelated) "collective"
      observables by diagonalizing this matrix. Symmetry properties of such
      eigenvectors are discussed. Often also, however, while the existence of an
      ultrametric tree is known, the degrees of parentage of the data are unknown,
      because a random perturbation confuses the labeling of the leaves of the tree. We
      sort out those observables which are more robust with respect to such labeling
      mistakes.

PMID- 11970675
TI  - Theoretical electroencephalogram stationary spectrum for a white-noise-driven
      cortex: evidence for a general anesthetic-induced phase transition.
AB  - We present a model for the dynamics of a cerebral cortex in which inputs to
      neuronal assemblies are treated as random Gaussian fluctuations about a mean
      value. We incorporate the effect of general anesthetic agents on the cortex as a
      modulation of the inhibitory neurotransmitter rate constant. Stochastic
      differential equations are derived for the state variable h(e), the average
      excitatory soma potential, coherent fluctuations of which are believed to be the
      source of scalp-measured electroencephalogram (EEG) signals. Using this
      stochastic approach we derive a stationary (long-time limit) fluctuation spectrum
      for h(e). The model predicts that there will be three distinct stationary
      (equilibrium) regimes for cortical activity. In region I ("coma"), corresponding
      to a strong inhibitory anesthetic effect, h(e) is single valued, large, and
      negative, so that neuronal firing rates are suppressed. In region II for a zero
      or small anesthetic effect, h(e) can take on three values, two of which are
      stable; we label the stable solutions as "active" (enhanced firing) and
      "quiescent" (suppressed firing). For region III, corresponding to negative
      anesthetic (i.e., analeptic) effect, h(e) again becomes single valued, but is now
      small and negative, resulting in strongly elevated firing rates ("seizure"). If
      we identify region II as associated with the conscious state of the cortex, then
      the model predicts that there will be a rapid transit between the active
      conscious and comatose unconscious states at a critical value of anesthetic
      concentration, suggesting the existence of phase transitions in the cortex. The
      low-frequency spectral power in the h(e) signal should increase strongly during
      the initial stage of anesthesia induction, before collapsing to much lower values
      after the transition into comatose-unconsciousness. These qualitative predictions
      are consistent with clinical measurements by Buhrer et al. [Anaesthesiology 77,
      226 (1992)], MacIver et al. [ibid. 84, 1411 (1996)], and Kuizenga et al. [Br. J.
      Anaesthesia 80, 725 (1998)]. This strong increase in EEG spectral power in the
      vicinity of the critical point is similar to the divergences observed during
      thermodynamic phase transitions. We show that the divergence in low-frequency
      power in our model is a natural consequence of the existence of turning points in
      the trajectory of stationary states for the cortex.

PMID- 11970677
TI  - Categorization in fully connected multistate neural network models.
AB  - The categorization ability of fully connected neural network models, with either
      discrete or continuous Q-state units, is studied in this work in replica
      symmetric mean-field theory. Hierarchically correlated multistate patterns in a
      two level structure of ancestors and descendents (examples) are embedded in the
      network and the categorization task consists in recognizing the ancestors when
      the network is trained exclusively with their descendents. Explicit results for
      the dependence of the equilibrium properties of a Q=3-state model and a
      Q=infinity-state model are obtained in the form of phase diagrams and
      categorization curves. A strong improvement of the categorization ability is
      found when the network is trained with examples of low activity. The
      categorization ability is found to be robust to finite threshold and synaptic
      noise. The Almeida-Thouless lines that limit the validity of the replica
      symmetric results, are also obtained.

PMID- 11970678
TI  - Scaling and percolation in the small-world network model.
AB  - In this paper we study the small-world network model of Watts and Strogatz, which
      mimics some aspects of the structure of networks of social interactions. We argue
      that there is one nontrivial length-scale in the model, analogous to the
      correlation length in other systems, which is well-defined in the limit of
      infinite system size and which diverges continuously as the randomness in the
      network tends to zero, giving a normal critical point in this limit. This length
      scale governs the crossover from large- to small-world behavior in the model, as
      well as the number of vertices in a neighborhood of given radius on the network.
      We derive the value of the single critical exponent controlling behavior in the
      critical region and the finite size scaling form for the average vertex-vertex
      distance on the network, and, using series expansion and Pade approximants, find
      an approximate analytic form for the scaling function. We calculate the effective
      dimension of small-world graphs and show that this dimension varies as a function
      of the length-scale on which it is measured, in a manner reminiscent of
      multifractals. We also study the problem of site percolation on small-world
      networks as a simple model of disease propagation, and derive an approximate
      expression for the percolation probability at which a giant component of
      connected vertices first forms (in epidemiological terms, the point at which an
      epidemic occurs). The typical cluster radius satisfies the expected finite size
      scaling form with a cluster size exponent close to that for a random graph. All
      our analytic results are confirmed by extensive numerical simulations of the
      model.

PMID- 11970679
TI  - Statistical analysis of ionic current fluctuations in membrane channels.
AB  - The statistical analysis of an ionic current signal recorded from a single
      channel of a biological membrane is presented. We find the main characteristics
      of the ionic current probability density, the closed- and open-state
      distributions, and the autocorrelation function of the current recordings by
      using procedures based on the kernel and tail estimators, the bootstrap
      methodology; and the Zipf plots. The results provide evidence for the non
      Markovian character of the channel kinetics of the investigated data.

PMID- 11970680
TI  - Role of soft and hard aggregates in the thermodynamics of lipid dispersions.
AB  - We study the thermodynamics of a two-dimensional polydisperse ideal gas model of
      different species of aggregates. We show that if these aggregates are
      distinguished not only by their sizes but also by their ability to display shape
      fluctuations, the system presents dominance of one or other species, depending on
      the temperature region. This result, which emerges solely from the statistics of
      the model in total absence of interaggregate interactions, describes well the
      observed temperature dependence of light scattering in dispersions of dimyristoyl
      phosphatidylglycerol, a negatively charged lipid.

PMID- 11970681
TI  - Power-law fluctuations in phase-separated lipid membranes.
AB  - The spatial structure of three binary lipid mixtures, prepared as multilamellar
      vesicles, was studied by small-angle neutron scattering. In the fluid-gel
      coexistence region, large-scale concentration fluctuations appear which scatter
      like surface fractals for small acyl-chain mismatch and like mass fractals for
      large mismatch over about one decade of length. The transition is highly
      discontinuous: The fractal dimension of the boundary between the gel and fluid
      drops from 2.7 to 1.7, the gel fraction in the fluctuations drops from about 0.5
      to 0.07, and the gel domains interlamellar correlation drops from strong to weak.
      We interpret the fluctuations as long-lived descendants of the incipient two
      phase equilibrium state and the transition as due to changes in the gel rigidity
      and phase diagram.

PMID- 11970682
TI  - Electron kinetic effects in atmosphere breakdown by an intense electromagnetic
      pulse.
AB  - A physical model is proposed for description of electron kinetics driven by a
      powerful electromagnetic pulse in the Earth's atmosphere. The model is based on a
      numerical solution to the Boltzmann kinetic equation for two groups of electrons.
      Slow electrons (with energies below a few keV) are described in a two-term
      approximation assuming a weak anisotropy of the electron distribution function.
      Fast electrons (with energies above a few keV) are described by a modified
      macroparticle method, taking into account the electron acceleration in the
      electric field, energy losses in the continuous deceleration approximation, and
      the multiple pitch angle scattering. The model is applied to a problem of the
      electric discharge in a nitrogen, which is preionized by an external gamma-ray
      source. It is shown that the runaway electrons have an important effect on the
      energy distribution of free electrons, and on the avalanche ionization rate. This
      mechanism might explain the observation of multiple lightning discharges observed
      in the Ivy-Mike thermonuclear test in the early 1950's.

PMID- 11970683
TI  - Equilibrium and oscillations of grains in the dust-plasma crystal.
AB  - The dispersion characteristics of the low-frequency mode associated with vertical
      oscillations of dust grains in a quasi-two-dimensional dust-plasma crystal are
      calculated, taking into account the dependence of the dust charge on the local
      sheath potential. It is shown that the equilibrium of the dust grains close to
      the electrode may be disrupted by large amplitude vertical oscillations.

PMID- 11970684
TI  - Absorption of subpicosecond UV laser pulses during interaction with solid
      targets.
AB  - The absorption of subpicosecond uv laser pulses has been measured at intensities
      above 10(17) W/cm(2). High levels of absorption were observed, up to 55% for s
      polarization and 65% for p polarization. The behavior with angle of incidence and
      polarization can be interpreted as due to a combination of resonance and
      collisional absorption, taking place in a plasma with a scale length of the order
      of a fraction of the laser wavelength.

PMID- 11970685
TI  - Space-dependent aspects of electron degradation.
AB  - Space- and energy-dependent flux densities were computed by a Monte Carlo method
      of electron degradation for 0.1-3.0 keV incident electrons in argon. These flux
      densities contain the basic information about the electron degradation process
      and can be used to calculate a yield for any inelastic state at any spatial
      position. Numerical results were analytically represented in terms of the
      recently introduced phenomenological model. It was found that flux densities
      multiplied by an absorption cross section in argon are approximately the same as
      flux densities multiplied by an absorption cross section in nitrogen. This
      feature provides a basis to use an analytical approximation of flux densities
      from this study for any gas.

PMID- 11970686
TI  - Theory of beam-plasma instability in a periodic plasma-filled waveguide.
AB  - The beam-plasma wave interaction in a periodic plasma-filled waveguide is treated
      in a mathematically correct manner on the basis of the integral equation (IE)
      method. It has been shown that the relevant boundary-value problem could be
      reduced to an IE with a singular kernel for the longitudinal component of the
      electric field on the waveguide axis. The regularization of the IE was performed
      by extracting the static part of the kernel. The resulting IE of the second kind
      with a regular kernel, being rather convenient for a numerical analysis, is
      treated in a quasistatic approximation as a spectral problem. First-order
      expressions for eigenfunctions, and an infinite set of dispersion relations
      linking a wave number and frequency of plasma oscillations which separate radial
      branches of plasma oscillations from axial ones, have been obtained in the closed
      analytical form, thus enabling us to avoid the problem with the so-called "dense"
      spectrum. The solutions of the relevant "cold" dispersion relations establish a
      periodical dependence of the frequency on the wave number over several periods
      within the accuracy of order of the neglected terms. In the presence of an
      electron beam they turn out to be unstable near frequencies providing the
      resonances of the beam with spatial plasma harmonics. Evaluations of the
      instability saturation level predict a more efficient beam-plasma wave energy
      transfer compared with those following from a conventional theoretical analysis
      based on the formulation of a dispersion relation in terms of an infinite
      determinant, with following truncation of the latter to the finite sized
      relation.

PMID- 11970687
TI  - Quasilinear theory of collisionless Fermi acceleration in a multicusp magnetic
      confinement geometry.
AB  - Particle motion in a cylindrical multiple-cusp magnetic field configuration is
      shown to be highly (though not completely) chaotic, as expected by analogy with
      the Sinai billiard. This provides a collisionless, linear mechanism for phase
      randomization during monochromatic wave heating. A general quasilinear theory of
      collisionless energy diffusion is developed for particles with a Hamiltonian of
      the form H0+H1, motion in the unperturbed Hamiltonian H0 being assumed chaotic,
      while the perturbation H1 can be coherent (i.e., not stochastic). For the
      multicusp geometry, two heating mechanisms are identified-cyclotron resonance
      heating of particles temporarily mirrortrapped in the cusps, and nonresonant
      heating of nonadiabatically reflected particles (the majority). An analytically
      solvable model leads to an expression for a transit-time correction factor,
      exponentially decreasing with increasing frequency. The theory is illustrated
      using the geometry of a typical laboratory experiment.

PMID- 11970688
TI  - Kinetic theory of Jeans instability of a dusty plasma.
AB  - A kinetic theory of the Jeans instability of a dusty plasma has been developed in
      the present work. The effect of grain charge fluctuations due to the attachment
      of electrons and ions to the grain surface has been considered in the framework
      of Krook's collisional model. We demonstrate that the grain charge fluctuations
      alter the growth rate of the gravitational collapse of the dusty plasma. The
      Jeans length has been derived under limiting cases, and its dependence on the
      attachment frequency is shown. In the absence of gravity, we see that the damping
      rate of the dust acoustic mode is proportional to the electron-dust collision
      frequency.

PMID- 11970689
TI  - High negative charge of a dust particle in a hot cathode discharge.
AB  - Dust particle levitation experiments in a plasma produced by a hot filament
      discharge, operating at low argon pressure, are presented. The basic
      characteristics of a dust grain trapped in a plate sheath edge in these
      experimental conditions are reported. Taking into account the sheath potential
      profiles measured with a differential emissive probe diagnostic, the forces
      applied to an isolated dust grain can be determined. Two different experimental
      methods yield approximately the same value for the dust charge. The observed high
      negative charge is mainly due to the contribution of the primary electrons
      emitted by the filaments as predicted by a simple model.

PMID- 11970690
TI  - Self-organization in a dissipative three-wave interaction.
AB  - A nonlinear three-wave interaction in an open dissipative plasma model of a
      stimulated Raman backscattering is studied. An anomalous kinetic dissipation due
      to electron trapping and plasma wave breaking is accounted for in a hybrid
      kinetic-fluid scheme. We simulate a finite plasma with open boundaries and vary a
      transport parameter to examine a route to spatio-temporal complexity. An
      interplay between self-organization at micro (kinetic) and macro (fluid) scales
      is found through quasi-periodic and intermittent evolution of dynamical
      variables, dissipative structures and related entropy rates. A consistency with a
      general scenario of self-organization is claimed.

PMID- 11970691
TI  - Stationary periodic and solitary waves induced by a strong short laser pulse.
AB  - The propagation of a relatively intense short laser pulse into an isotropic
      plasma is described. A kinetic equation for the spectral function of the
      electromagnetic waves is derived for an arbitrary amplitude pump wave, where the
      fully relativistic case is considered. The resulting kinetic equation of the
      spectral function is used along with the set of equations of the plasma to derive
      a general dispersion relation, where relativistic effects play an important role.
      In the case of a super-strong short laser pulse, Langmuir waves, with phase
      velocities larger than the speed of light, and waves of ion-sound type, which are
      damped only on ions, are found. In addition, for the case when the plasma density
      along with the mass of the electrons satisfies the "frozen-in" condition,
      stationary nonlinear new type of ion-sound waves are investigated. The mechanism
      of the emission of these waves is also discussed.

PMID- 11970692
TI  - Laser-assisted stopping power of a hot plasma for a system of correlated ions.
AB  - The laser-assisted stopping power of a fully ionized plasma for the system of two
      correlated test charges is investigated. The general expressions for the stopping
      power are applied to a low-density and a low-temperature plasma in a low-energy
      beam-plasma experiment [J. Jacoby et al., Phys. Rev. Lett. 74, 1550 (1995)]. The
      effect of the interaction between the beam test charges, described by a
      correlation term, is to increase the stopping power of the laser-assisted plasma
      compared to the case where the charges are infinitely separated. However, the
      laser field affects the correlation between the test charges and contributes to
      decrease the plasma stopping power, as compared to the laser-free dicluster case.

PMID- 11970693
TI  - Ion-molecule reactions and ion energies in a CF4 discharge.
AB  - Absolute cross sections have been measured for reactants typically found in
      carbon tetrafluoride (CF(4)) discharges for collision energies below a few
      hundred electron volts. The reactions investigated include collision-induced
      dissociation and dissociative electron transfer reactions for CF(+)(3) and F(+)
      colliding with CF(4), and collisional electron detachment for F(-) colliding with
      CF4. Also presented are measurements of energies and relative intensities of ions
      generated in dc Townsend CF4 discharges with E/N values ranging from 4 x 10(-18)
      V m(2) to 25 x 10(-18) V m(2) [4 to 25 kTd]. Ion energy and ion intensity data
      for the Townsend discharges are analyzed in light of the measured cross sections.

PMID- 11970694
TI  - Nonconservative charged-particle swarms in ac electric fields.
AB  - A time-dependent multi-term technique has been developed and employed to solve
      the space- and time-dependent Boltzmann equation for charged-particle swarms in
      ac electric fields. This technique allows for the accurate calculation of both
      the full set of transport coefficients and the phase-space distribution function.
      This technique avoids restrictions on the field amplitude and frequency and/or
      the charged-particle to neutral molecule mass ratio traditionally associated with
      many contemporary investigations. To our knowledge, it represents the first
      rigorous treatment of the explicit effects of nonconservative processes on
      transport coefficients in ac electric fields. The phenomena associated with these
      explicit effects of nonconservative processes are striking (e.g., negative phase
      lags in the drift velocity for an attaching gas), and the errors associated with
      traditional treatments of ionization and attachment on the transport coefficients
      are highlighted.

PMID- 11970695
TI  - High-intensity laser-induced electron acceleration in vacuum.
AB  - In this paper, an approximate pulsed-laser-beam solution of Maxwell's equation in
      vacuum is derived. Then with the numerical simulation method, electron
      acceleration induced by high-intensity [Q(0)=eE(0)/(m(e)omega c)=3] lasers is
      discussed in connection with the recent experiment of Malka et al. It is found
      that the maximum energy gain and the relationship between the final energy and
      the scattering angle can be well reproduced, but the polarization effect of
      electron-laser interactions is not very prominent. These results show that the
      ponderomotive potential model is still applicable, which means that the
      stimulated Compton scattering is the main fundamental mechanism responsible for
      the electron acceleration at this laser intensity.

PMID- 11970696
TI  - Effects of resonances on halo formation in high-intensity storage rings.
AB  - Numerical calculations for the Spallation Neutron Source accumulator ring
      indicate that lattice resonances excited by the space-charge potential can
      increase a mismatch significantly by deforming the beam distribution in phase
      space. Hence increased mismatch leads to enhanced envelope oscillations that are
      driving the 2:1 parametric resonance leading to halo formation, even for
      initially matched beams. We have observed this behavior for the 2 nu(x) - 2 nu(y)
      = 0 resonance and for the 4 nu(y) = 23 resonance. This mechanism for halo
      formation peculiar to rings through resonance driven mismatch is very sensitive
      to the tunes, which emphasizes the importance of a careful choice of operating
      point in tune space.

PMID- 11970697
TI  - Dissipative lattice model with exact traveling discrete kink-soliton solutions:
      discrete breather generation and reaction diffusion regime.
AB  - We introduce a nonlinear Klein-Gordon lattice model with specific double-well on
      site potential, additional constant external force and dissipation terms, which
      admits exact discrete kink or traveling wave fronts solutions. In the non
      dissipative or conservative regime, our numerical simulations show that narrow
      kinks can propagate freely, and reveal that static or moving discrete breathers,
      with a finite but long lifetime, can emerge from kink-antikink collisions. In the
      general dissipative regime, the lifetime of these breathers depends on the
      importance of the dissipative effects. In the overdamped or diffusive regime, the
      general equation of motion reduces to a discrete reaction diffusion equation; our
      simulations show that, for a given potential shape, discrete wave fronts can
      travel without experiencing any propagation failure but their collisions are
      inelastic.

PMID- 11970698
TI  - Dynamics of a misaligned astigmatic twisted Gaussian beam in a Kerr-nonlinear
      parabolic waveguide.
AB  - Using the Galerkin criterion in the basis of flexible generalized Gaussian modes,
      the equations of motion are derived for the parameters of a misaligned astigmatic
      twisted Gaussian beam in an axially symmetric nonlinear medium. Nontrivial
      features of the beam dynamics (e.g., phase locking, cycle generation, nonlinear
      symmetry change) in a parabolic waveguide with Kerr nonlinearity are revealed.

PMID- 11970699
TI  - Matrix formulation for the propagation of light beams with orbital and spin
      angular momenta.
AB  - Jones matrices describe the polarization, or spin angular momentum, of a light
      beam as it passes through an optical system. We devise an equivalent of the Jones
      matrix formulation for light possessing orbital angular momentum. The matrices
      are then developed to account for light that has both spin and orbital angular
      momentum.

PMID- 11970700
TI  - Linear stability analysis of walking vector solitons.
AB  - The linear stability analysis of two-parameter families of walking vector
      solitons of coupled nonlinear Schrodinger equations is performed. It is shown
      that the eigenvalues of the corresponding linearized problem can be complex
      valued in certain regions of the parameter space. The complex nature of the
      associated Lyapunov eigenvalues leads to a quite complicated pattern of
      instability regions of lowest-order soliton types. This pattern includes two
      typical situations: (i) the relevant eigenmode has a purely imaginary eigenvalue
      that passes through zero at the critical point and then becomes purely real, and
      (ii) the interplay between two discrete eigenmodes having purely imaginary
      eigenvalues leads to a bifurcation scenario where two imaginary eigenvalues merge
      together and become complex at the bifurcation point. It is shown that all known,
      lowest-order soliton types, namely slow, fast, in-phase vector, and out-of-phase
      vector, are dynamically stable in certain regions of the parameter space.

PMID- 11970701
TI  - Role of internal and continuum modes in modulational instability of quadratic
      solitons.
AB  - The role of internal and continuum modes in the modulational instability of
      spatial quadratic solitons is examined by asymptotic and numerical analyses. It
      is shown that these modes generate novel spatially symmetric and asymmetric
      modulation instability branches, which underline soliton dynamics throughout a
      wide region of the wave-vector mismatch.

PMID- 11970702
TI  - Modulational instability of multiple-charged optical vortex solitons under
      saturation of the nonlinearity.
AB  - We present a linear analysis and numerical simulations of the instability of
      optical vortex solitons (OVSs) of arbitrary topological charge. They show a rich
      variety of instability scenarios depending on the type of perturbation. The
      saturation of the nonlinearity is shown to be able to slow down the decay of
      multiple charged dark beams at an intermediate evolution stage and to prevent
      their ultimate decay into charge-1 OVSs. This concept is experimentally verified
      by the observation of a partial decay of a triple-charged OV beam and by
      comparing this dynamic with the behavior of OV beams of topological charges m=1,
      2, 3, and 4.

PMID- 11970703
TI  - Motion of compactonlike kinks.
AB  - We analyze the ability of a compactonlike kink (i.e., kink with compact support)
      to execute a stable ballistic propagation in a discrete Klein-Gordon system with
      anharmonic coupling. We demonstrate that the effects of lattice discreteness, and
      the presence of a linear coupling between lattice sites, are detrimental to a
      stable ballistic propagation of the compacton, because of the particular
      structure of the small-oscillation frequency spectrum of the compacton in which
      the lower-frequency internal modes enter in direct resonance with phonon modes.
      Our study reveals the parameter regions for obtaining a stable ballistic
      propagation of a compactonlike kink. Finally we investigate the interactions
      between compactonlike kinks.

PMID- 11970704
TI  - Group theory used to improve the efficiency of transfer-matrix computations.
AB  - Transfer-matrix methodology is frequently used to deal with elastic scattering
      problems that require a solution of Schrodinger or homogeneous Maxwell equations
      in the continuous part of their spectra. As predicted by group theory, the basic
      states used for the expansion of the solutions can be separated into independent
      sets, thus enabling the scattering problem to be solved with a drastically
      improved efficiency. Depending on the peculiar symmetry in the problem, the basic
      states can present pairs of "conjugate sets," whose associated characters are
      complex conjugate of each other. When the potential energy takes strict real
      values, the transfer matrices corresponding to these conjugate sets have well
      defined relationships that enable the transfer matrices of both conjugate sets to
      be computed from a single propagation step. This results in a further reduction
      of up to 50% of the total computation time. This paper presents the way group
      theory can be used systematically to improve the efficiency of transfer-matrix
      computations. In a first part, the basic states are separated into independent
      sets. Relationships between the transfer matrices corresponding to conjugate sets
      are then derived. The theory is finally illustrated by a simulation of electronic
      scattering by a C60 molecule in a projection configuration.

PMID- 11970705
TI  - Monte Carlo simulations of non-Fickian water transport in a saturated porous gel.
AB  - A Monte Carlo algorithm, which incorporates tensile effects as well as diffusion,
      is proposed. It provides a description of water transport in a drying porous gel
      close to saturation permitting an interpretation of magnetic resonance imaging
      profiles. Boltzmann's transformation of the one-dimensional diffusion equation is
      employed to examine the onset of a non-Fickian transport regime caused by the
      collective motion of diffusers associated with tensile forces.

PMID- 11970706
TI  - Van der Waals type loop in microcanonical caloric curves of finite systems.
AB  - The entropy is usually related to the energy density of states. This relation is
      approximate for the finite systems (clusters) and an exact relation connects the
      entropy with the phase volume of the system. These relations give the same
      results only in the thermodynamic limit. We consider the microcanonical caloric
      curves determined via both the approximate and exact relations. It is proved that
      if the caloric curve obtained from the exact relation has a van der Waals type
      loop (or S bend), then the caloric curve obtained from the approximate relation
      has S-bend, and the reverse statement is not correct. Using properties of the
      system at low and high energies we have shown that a van der Waals type loop in
      the caloric curve of the finite system requires a positive value of the second
      derivative of the logarithm of the canonical total energy distribution function
      at least at one value of the energy. The latter is the weaker necessary condition
      for S-bend to occur in the caloric curve than that obtained earlier.

PMID- 11970707
TI  - Surface restructuring and kinetic oscillations in heterogeneous catalytic
      reactions.
AB  - We extend our earlier Monte Carlo simulations of isothermal kinetic oscillations
      in the NO-H(2)/Pt(100) system [V. P. Zhdanov, Phys. Rev. E 59, 6292 (1999)]. The
      analysis, based on a lattice-gas model describing surface restructuring in terms
      of the statistical theory of first-order phase transitions, is primarily focused
      on adsorbate-diffusion-mediated synchronization of oscillations. The conventional
      condition for synchronization, (D tau)(1/2)>L (D is the diffusion coefficient,
      tau the oscillation period, and L the lattice size), is proved to considerably
      underestimate the role of surface diffusion. Due to the formation of mesoscopic
      islands, well developed oscillations are found to be possible in the cases when
      the left part of this condition is much lower than the right part.

PMID- 11970708
TI  - Test of renormalization predictions for universal finite-size scaling functions.
AB  - We calculate universal finite-size scaling functions for systems with an n
      component order parameter and algebraically decaying interactions. Just as
      previously found for short-range interactions, this leads to a singular epsilon
      expansion, where epsilon is the distance to the upper critical dimension.
      Subsequently, we check the results by numerical simulations of spin models in the
      same universality class. Our systems offer the essential advantage that epsilon
      can be varied continuously, allowing an accurate examination of the region where
      epsilon is small. The numerical calculations turn out to be in striking
      disagreement with the predicted singularity.

PMID- 11970709
TI  - Diffusion through piecewise washboard potential.
AB  - We consider the influence of small periodic oscillations of barriers on the
      stationary motion of a particle through a piecewise washboard potential. Up to
      the second order in the amplitude of oscillation the corrections to the flux can
      be both positive and negative and, for equal widths of the well and barrier, they
      do not depend on the frequency of the oscillations.

PMID- 11970710
TI  - Modified renormalization strategy for sandpile models.
AB  - Following the renormalization-group scheme recently developed by Pietronero et
      al. [Phys. Rev. Lett. 72, 1690 (1994)] we introduce a simplifying strategy for
      the renormalization of the relaxation dynamics of sandpile models. In our scheme,
      five subcells at a generic scale b form the renormalized cell at the next larger
      scale. Now the fixed point has a unique nonzero dynamical component that allows
      for a great simplification in the computation of the critical exponent z. The
      values obtained are in good agreement with both numerical and theoretical results
      previously reported.

PMID- 11970711
TI  - Arrested cracks in nonlinear lattice models of brittle fracture.
AB  - We generalize lattice models of brittle fracture to arbitrary nonlinear force
      laws and study the existence of arrested semi-infinite cracks. Unlike what is
      seen in the discontinuous case studied to date, the range in driving displacement
      for which these arrested cracks exist is very small. Also, our results indicate
      that small changes in the vicinity of the crack tip can have an extremely large
      effect on arrested cracks. Finally, we briefly discuss the possible relevance of
      our findings to recent experiments.

PMID- 11970712
TI  - Broad-band colored noise: digital simulation and dynamical effects.
AB  - We propose a broad-band colored noise, which allows the transition between "red"
      and "green" noises. A double-integral algorithm for solving the Langevin equation
      with this noise is developed. The steady currents of an overdamped particle
      moving in the correlation and diffusion ratchets are calculated. It is shown that
      the flow reverses sign when the external noise is filtered off in the region of
      low frequencies to a sufficient extent. The present noise is also compared with
      the Ornstein-Uhlenbeck colored noise and the harmonic noise.

PMID- 11970713
TI  - Hamiltonian for a restricted isoenergetic thermostat.
AB  - Nonequilibrium molecular dynamics simulations often use mechanisms called
      thermostats to regulate the temperature. A Hamiltonian is presented for the case
      of the isoenergetic (constant internal energy) thermostat corresponding to a
      tunable isokinetic (constant kinetic energy) thermostat, for which a Hamiltonian
      has recently been given.

PMID- 11970714
TI  - Absence of chaos in Bohmian dynamics.
AB  - The Bohm motion for a particle moving on the line in a quantum state that is a
      superposition of n+1 energy eigenstates is quasiperiodic with n frequencies.

PMID- 11970715
TI  - Immense delocalization from fractional kinetics.
AB  - We observe immense delocalization of the order of 10(9) for a kicked Harper model
      when a control parameter K is taken to be K*=6.349 972. This "magic" value
      corresponds to special phase space topology in the classical limit, when a
      hierarchical self-similar set of sticky islands emerges. The origin of the effect
      is of the general nature and similar immense delocalization can be found in other
      systems.

PMID- 11970716
TI  - Coupled modified baker's transformations for the Ising model.
AB  - An invertible coupled map lattice is proposed for the Ising model. Each elemental
      map is a modified baker's transformation, which is a two-dimensional map of X and
      Y. The time evolution of the spin variable is memorized in the binary
      representation of the Y variable. The temporal entropy and time correlation of
      the spin variable are calculated from the snapshot configuration of the Y
      variables.

PMID- 11970717
TI  - Electro-aerodynamic instability of a thin dielectric liquid sheet sprayed with an
      air stream.
AB  - The instability of a thin sheet of dielectric liquid moving in the same direction
      as an air stream in the presence of a uniform horizontal electric field is
      studied theoretically. It is found that aerodynamic-enhanced instability occurs
      if the Weber number is much less than a critical value related to the ratio of
      the air and liquid stream velocities, the electric field, and the dielectric
      constant values. The electric field is found to have a stabilizing effect, and
      there exists a critical Weber number above which instability is suppressed by the
      surface tension effect. The condition for disintegrating the sheet is obtained in
      terms of the electric field values, and some limiting cases are recovered.

PMID- 11970718
TI  - Simple and accurate theory for strong shock waves in a dense hard-sphere fluid.
AB  - Following an earlier work by Holian et al. [Phys. Rev. E 47, R24 (1993)] for a
      dilute gas, we present a theory for strong shock waves in a hard-sphere fluid
      described by the Enskog equation. The idea is to use the Navier-Stokes
      hydrodynamic equations but taking the temperature in the direction of shock
      propagation rather than the actual temperature in the computation of the
      transport coefficients. In general, for finite densities, this theory agrees much
      better with Monte Carlo simulations than the Navier-Stokes and (linear) Burnett
      theories, in contrast to the well-known superiority of the Burnett theory for
      dilute gases.

PMID- 11970719
TI  - Fluctuation modes in confined nematic liquid crystals in a regime of critical
      wetting.
AB  - Analytic solutions are obtained for the energies of normal fluctuation modes in
      confined nematic liquid crystals in a regime of critical wetting. The expressions
      are valid close enough to the nematic-isotropic phase-transition temperature and
      demonstrate that the spectra of local director modes give direct information
      about the nature of presurface forces and the criticality by itself. The possible
      changes in the spectra imposed by interface-position fluctuations and order
      electricity effects are also discussed.

PMID- 11970720
TI  - Dynamics of pinned interfaces with inertia.
AB  - We introduce velocity dependent pinning into two models which are known to be in
      the universality class of the directed percolation depinning (DPD) model. The
      effective internal force acting on any point of the interface is enchanced by a
      factor f at that point of the interface which has last moved. This causes the
      effective roughness exponent to cross over continuously from the DPD value of
      0.63, to unity in the non-dissipative limit of f-->infinity, while the growth
      exponent tends to 3/4. DPD scaling is recovered for length scales above a
      persistence length which grows with the enchancement factor as f(psi), with a new
      exponent psi approximately equal to 1.3.

PMID- 11970722
TI  - Stability of neural networks and solitons of field theory.
AB  - The layers of a feed-forward neural network are interpreted as a cascade of field
      theories. The stability of the neural network is interpreted as the topological
      stability of kink solutions. An explicit example is shown for a three-class
      problem with their field theoretical Lagrangian equations.

PMID- 11970723
TI  - Electromagnetic convective cells in a nonuniform dusty plasma.
AB  - It is noticed that in the presence of a perturbed electron current parallel to an
      external magnetic field, the dispersion relation of the electrostatic convective
      cell and the magnetostatic modes are not modified, contrary to the result quoted
      in the literature. Instead, the electrostatic and magnetostatic modes are coupled
      if the propagation parallel to the magnetic field is taken into account in both
      dusty and electron-ion plasmas.

PMID- 11970721
TI  - Proton glass freezing in hydrated lysozyme powders.
AB  - At room temperature, the dielectric relaxation of hydrated powder of the protein
      lysozyme is known to be due to protons migrating between ionized side chains. A
      recent study of this relaxation at lower temperatures suggested a behavior
      typical of proton glasses. An analysis of the complex dielectric susceptibility
      by a temperature-frequency plot presented here has revealed that ergodicity is
      broken due to the divergence of the longest relaxation time at 266 K, indicating
      specifically that this hydrated protein is a proton glass. A change in the
      temperature behavior of the static dielectric constant and the average relaxation
      frequency at 273 K indicates a further transition occurring at this temperature,
      whose nature remains to be investigated.

PMID- 11970724
TI  - Calculation of electromagnetic properties of regular and random arrays of
      metallic and dielectric cylinders.
AB  - A method is developed to calculate electromagnetic properties of arrays of
      metallic and dielectric cylinders. It incorporates and exploits cylindrical
      boundary conditions and Rayleigh identities for efficient, high-accuracy
      calculation of scattering off individual layers that are stacked into arrays
      using scattering matrices. The method enables absorption, dispersion, and
      randomness to be incorporated efficiently, and reproduces known results with
      vastly improved speed and accuracy. It is used to demonstrate existence of states
      introduced into photonic band gaps of a dielectric array by disorder, and
      anomalous absorption behavior in arrays of aluminum cylinders.

PMID- 11970725
TI  - Soliton-breather reaction pathways.
AB  - We use a collective coordinate approach to investigate corpuscular properties of
      breathers in nonlinear lattice systems. We calculate the breather internal energy
      and inertial mass and use them to analyze the reaction pathways of breathers with
      kinks that are preformed in the lattice. We find that there is an effective kink
      breather intraction potential that, under some circumstances, is attractive and
      has a double well shape. Furthermore, we find that in some cases the internal
      energy of a moving breather can be released during the reaction with the kink and
      subsequently transformed to kink translational energy. These breather properties
      seem to be model independent.

PMID- 11970726
TI  - Spatiotemporal dynamics of electromagnetic pulses in saturating nonlinear optical
      media with normal group velocity dispersion.
AB  - The nonlinear dynamics of ultrashort optical pulses in nonlinear saturating media
      with normal group velocity dispersion is examined. The studied saturating
      nonlinearity changes the sign at the peak intensity of the laser pulses. In the
      bulk media and the planar wave guides the temporal collapse of the pulse is
      arrested by its splitting in spatial domain leading to rings formation. The wave
      collapse in one dimensional geometry cannot be arrested; the field singularity
      develops for a finite propagation distance.

PMID- 11970727
TI  - Efficient Monte Carlo simulations using a shuffled nested Weyl sequence random
      number generator.
AB  - The pseudorandom number generator proposed recently by Holian et al. [B. L.
      Holian, O. E. Percus, T. T. Warnock, and P. A. Whitlock, Phys. Rev. E 50, 1607
      (1994)] is tested via Monte Carlo computation of the free energy difference
      between the defectless hcp and fcc hard sphere crystals by the Frenkel-Ladd
      method [D. Frenkel and A. J. C. Ladd, J. Chem. Phys. 81, 3188 (1984)]. It is
      shown that this fast and convenient for parallel computing generator gives
      results in good agreement with results obtained by other generators. An estimate
      of high accuracy is obtained for the hcp-fcc free energy difference near melting.

PMID- 11970728
TI  - Reactive oxygen species and regulation of gene expression.
AB  - In eucaryotic cells reactive oxygen species (ROS) are produced in the reactions
      catalyzed by NAD(P)H oxidase and by some other specialized oxidases and also as
      an inevitable by-product of many redox reactions. Intracellular ROS synthesis is
      regulated by various hormones, cytokines, and growth factors. An increase in the
      ROS levels above a certain threshold (so-called oxidative stress) is accompanied
      by processes that are harmful for cell survival, such as lipid peroxidation and
      oxidative modification of proteins and nucleic acids. However, at low
      concentrations ROS act as secondary messengers responsible for a signal
      transduction from extracellular signaling molecules and their membrane receptors
      to the intracellular regulatory systems which control gene expression. Cellular
      transcriptional response to ROS is mediated mainly by activation of MAP protein
      kinases and submitted transcription factors AP-1, ATF, and NF-kappaB. A number of
      specific genes is also induced under hypoxia, i.e., under conditions opposite to
      oxidative stress. Cellular transcriptional response on hypoxia is mediated by
      activation of transcription factors HIF-1 and AP-1. Together with ROS, nitric
      oxide fulfills the role of a mobile and highly reactive redox-sensitive signaling
      molecule. Chemical reactions of NO with the superoxide anion and with other free
      radicals leads to production of highly reactive intermediates. Depending on the
      ratio of their intracellular concentrations, NO and ROS can either enhance or
      attenuate their reciprocal effects on cells.

PMID- 11970729
TI  - Nitric oxide cycle in mammals and the cyclicity principle.
AB  - This paper continues a series of reports considering nitric oxide (NO) and its
      cyclic conversions in mammals. Numerous facts are summarized with the goal of
      developing a general concept that would allow the statement of the multiple
      effects of NO on various systems of living organisms in the form of a short and
      comprehensive law. The current state of biological aspects of NO research is
      analyzed in term of elucidation of possible role of these studies in the system
      of biological sciences. The general concept is based on a notion on cyclic
      conversions of NO and its metabolites. NO cycles in living organisms and nitrogen
      turnover in the biosphere and also the Bethe nitrogen-carbon cycle in star matter
      are considered. A hypothesis that the cyclic organization of processes in living
      organisms and the biosphere reflects the evolution of life is proposed: the
      development of physiological functions and metabolism are suggested to be closely
      related to space and evolution of the Earth as a planet of the Solar System.

PMID- 11970730
TI  - Cytotoxic signal transduction pathways via TNF family receptors.
AB  - Studies indicating an important role of the TNF-receptor family in control of
      cell proliferation, differentiation, and death have drastically increased in
      number in recent years. The main function of many members of this family is cell
      death triggering, and this is apparently the only function for some of them.
      Studies on the molecular mechanisms of cell death activated by members of the TNF
      receptor family revealed and identified proteins directly or indirectly
      associated with TNF receptors. Pathways of cytotoxic signal transduction by some
      members of the TNF-Rs family based on currently proven protein-protein
      interactions and the role of distinct proteins in these processes are summarized
      in this review.

PMID- 11970731
TI  - Derivatives of benzotetrazine-1,3-dioxide are new NO-donors, activators of
      soluble guanylate cyclase, and inhibitors of platelet aggregation.
AB  - The ability of 5-nitro-, 7-nitro-, and 5,7-dinitrobenzotetrazine-1,3-dioxides to
      generate nitric oxide (NO) and activate soluble guanylate cyclase was
      investigated. All of these compounds were found to be thiol-dependent NO-donors
      and guanylate cyclase activators. The maximal stimulatory effect of 5-nitro-, 7
      nitro-, and 5,7-dinitrobenzotetrazine-1,3-dioxides was observed at 10 microM
      concentration and the activity increase was 4.5-, 15.0-, and 8.2-fold in the
      presence of 20 microM dithiothreitol and 11.3-, 31.6-, and 20.5-fold,
      respectively, in the presence of added glutathione (100 microM). The NO-dependent
      mechanism of benzotetrazine-1,3-dioxide nitroderivative-induced activation of
      soluble guanylate cyclase (in the presence of 100 microM glutathione) was
      confirmed by the inhibition (by 78%) of 7-nitrobenzotetrazine-1,3-dioxide (10
      microM)-stimulated guanylate cyclase activity in the presence of the NO-scavenger
      2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (Carboxy-PTIO,
      50 microM) and by the inhibition with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one
      (ODQ, 0.3 microM) of 5-nitro-, 7-nitro-, and 5,7-dinitrobenzotetrazine-1,3
      dioxides (10 microM)-stimulated guanylate cyclase by 34, 69, and 39%,
      respectively. All compounds used inhibited ADP-induced aggregation of human
      platelets with IC50 of 10.0, 1.3, and 2.0 microM for 5-nitro-, 7-nitro-, and 5,7
      dinitrobenzotetrazine-1,3-dioxides, respectively. A clearly defined correlation
      was established between the ability of the compounds to generate NO, activate
      soluble guanylate cyclase, and inhibit platelet aggregation.

PMID- 11970732
TI  - Study of the functional organization of a novel adenylate cyclase signaling
      mechanism of insulin action.
AB  - In this study we continued decoding the adenylate cyclase signaling mechanism
      that underlies the effect of insulin and related peptides. We show for the first
      time that insulin signal transduction via an adenylate cyclase signaling
      mechanism, which is attended by adenylate cyclase activation, is blocked in the
      muscle tissues of the rat and the mollusk Anodonta cygnea in the presence of: 1)
      pertussis toxin, which impairs the action of the inhibitory GTP-binding protein
      (Gi); 2) wortmannin, a specific blocker of phosphatidylinositol 3-kinase; and 3)
      calphostin C, an inhibitor of different isoforms of protein kinase C. The
      treatment of sarcolemmal membrane fraction with cholera toxin increases basal
      adenylate cyclase activity and decreases the sensitivity of the enzyme to
      insulin. We suggest that the stimulating effect of insulin on adenylate cyclase
      involves the following stages of hormonal signal transduction cascade: receptor
      tyrosine kinase --> Gi protein (betagamma) --> phosphatidylinositol 3-kinase -->
      protein kinase C (zeta?) --> Gs protein --> adenylate cyclase --> cAMP.

PMID- 11970733
TI  - Oxidative modification of proteins: oxidation of tryptophan and production of
      dityrosine in purified proteins using Fenton's system.
AB  - Specific features of metal-catalyzed oxidation (MCO) of purified proteins (human
      serum albumin and human erythrocyte superoxide dismutase) were analyzed by the
      oxidation level of tryptophan and tyrosine. The production of dityrosine cross
      links and the oxidation of tryptophan residues were recorded by fluorescence. The
      degree of oxidative modification of the amino acid residues of the proteins
      depended on the concentration of the Fenton's medium components and on the
      incubation time. These changes were different in different proteins. By
      electrophoresis and gel-permeation chromatography, changes in the superoxide
      dismutase structure are shown to be caused by oxidative modification of the
      enzyme and to be accompanied by a decrease in its activity. Findings with OH*
      scavengers (mannitol and ethanol) suggest that oxidative modification of the
      proteins in Fenton's medium should be associated not only with hydroxyl radical
      but also with ferryl and perferryl ions and with the radical CO(-.)(3).

PMID- 11970734
TI  - Hydrocarbons, fatty acids, and lipids of freshwater grasses of the
      Potamogetonaceae family.
AB  - The composition of hydrocarbons, fatty acids, and of total, polar, and neutral
      lipids was studied in freshwater Potamogetonaceae grasses collected in two
      different regions of the Volga river. More than 40 fatty acids and hydrocarbons
      were separated and identified by chromato-mass spectrometry. The variability of
      lipid characteristics of plants of the same family is discussed.

PMID- 11970735
TI  - Effect of synthetic beta-endorphin-like peptide immunorphin on human T
      lymphocytes.
AB  - Beta-endorphin and the synthetic beta-endorphin-like decapeptide Ser-Leu-Thr-Cys
      Leu-Val-Lys-Gly-Phe-Tyr (referred to as immunorphin), corresponding to the
      sequence 364-373 of the CH3 domain of human immunoglobulin G heavy chain, were
      shown to stimulate concanavalin A-induced proliferation of T lymphocytes from the
      blood of healthy donors. [Met(5)]Enkephalin and the antagonist of opioid
      receptors naloxone examined in parallel were inactive. The stimulating effect of
      beta-endorphin and immunorphin on T lymphocyte proliferation is not inhibited by
      naloxone. Studies on receptor binding of (125)I-labeled immunorphin to T
      lymphocytes revealed that it binds with high affinity to naloxone-insensitive
      receptors (K(d) = 7.0 +/- 0.3 nM). Unlabeled immunorphin completely inhibits
      (125)I-labeled beta-endorphin specific binding to naloxone-insensitive receptors
      on T lymphocytes (K(i) = 0.6 +/- 0.1 nM). Thus, beta-endorphin and immunorphin
      interact with common naloxone-insensitive receptors on T lymphocytes.

PMID- 11970736
TI  - A new pathway of photoinactivation of photosystem II. Irreversible photoreduction
      of pheophytin causes loss of photochemical activity of isolated D1-D2-cytochrome
      b559 complex.
AB  - A new pathway of photoinactivation of photosystem II (PS II) connected with
      irreversible photoaccumulation of reduced pheophytin (Ph) in isolated D1-D2
      cytochrome b559 complexes of reaction center (RC) of PS II was discovered. The
      inhibitory effects of white light illumination on photochemical activity of D1-D2
      cytochrome b559 complexes of RCs of photosystem II, isolated from pea
      chloroplasts, have been compared under anaerobic conditions in the absence and in
      the presence of sodium dithionite, electron transfer from which to the oxidized
      primary electron donor P680+ results in the photoaccumulation of anion-radical of
      the primary electron acceptor, Ph(-.). In both cases, prolonged illumination (1-5
      min, 120 W/m(2)) led to a pronounced loss of the photochemical activity as it was
      monitored by measuring the amplitude of the reversible photoinduced absorbance
      changes at 682 nm related to the photoreduction of Ph. The extent of the
      photoinactivation depended on the illumination time and pH of the medium. At pH
      8.0, the presence of dithionite during photoinactivation brought about a
      protective effect compared to that in a control sample. In contrast, lowering pH
      to 6.0 increased the sensitivity to photoinactivation in the dithionite
      containing samples. For 5 min irradiation, the photochemical activity in the
      absence and in the presence of dithionite decreased by 35 and 72%, respectively
      (this was accompanied by an irreversible bleaching of the pheophytin Q(x)
      absorption band at 542 nm). Degradation of the D1 and D2 proteins was not
      observed under these conditions. A subsequent addition of an electron acceptor,
      potassium ferricyanide, to the illuminated samples restored neither the amplitude
      of the signal at 682 nm nor absorption at 542 nm. It is suggested that at pH. 7.0
      the photoaccumulated Ph(-.) is irreversibly converted into a secondary, most
      probably protonated form, that does not lead to destruction of the RCs but
      prevents the photoformation of the primary radical pair [P680+Ph(-.)]. A possible
      application of this effect to photoinactivation of PS II in vivo is discussed.

PMID- 11970737
TI  - X-ray analysis of ribosomes: the static of the dynamic.
AB  - This review considers a brief history, comments, and consequences of recent
      remarkable achievements: X-ray analysis on the level of atomic resolution of
      structures of bacterial ribosomes, their subunits, and functional complexes.

PMID- 11970739
TI  - The choice of adjuvant combination therapies with taxanes: rationale and issues
      addressed in ongoing studies.
AB  - The taxanes are emerging as the most powerful compounds in breast cancer. Both
      compounds, paclitaxel and docetaxel, have been evaluated in the metastatic
      setting before proceeding with adjuvant trials. Docetaxel was shown in phase III
      trials to be superior, in particular, in terms of time to progression and
      survival, to salvage polychemotherapies after failure of prior chemotherapy
      including anthracyclines. Also, after failure of alkylating agents, a benefit in
      favor of docetaxel was reported when compared to doxorubicin, whereas paclitaxel
      was reported to be either as efficacious or inferior to doxorubicin, while being
      comparable to cyclophosphamide/methotrexate/5-fluorouracil. The role of taxanes
      in combination with anthracyclines in first-line therapy of advanced breast
      cancer is still unclear although emerging. One phase III trial showed the
      significant superiority of doxorubicin/docetaxel (AT) versus
      doxorubicin/cyclophosphamide (AC) in terms of response and time to progression.
      Several phase II studies with paclitaxel (over 3 hours) and anthracyclines in the
      metastatic setting showed high efficacy, but they also showed cardiac toxicity
      related to a pharmacokinetic interaction between the 2 agents. This fact led to
      the implementation of metastatic strategies (several phase III trials) aimed at
      avoiding the pharmacokinetic interaction or specifically limiting the cardiac
      toxicity that resulted in contradictory results. Consequently, adjuvant
      strategies with paclitaxel focused mostly on the sequential approach (AC followed
      by paclitaxel). In contrast, adjuvant strategies with docetaxel/anthracycline
      based programs were implemented following both sequential and combination
      approaches. Results of all of these trials in the adjuvant setting are eagerly
      awaited in order to establish the role of taxanes in adjuvant breast cancer.

PMID- 11970740
TI  - Combining the anti-HER2 antibody trastuzumab with taxanes in breast cancer:
      results and trial considerations.
AB  - Overexpression of the p185/HER2 protein is seen in 20%-25% of primary breast
      cancers and is associated with poor prognosis. Recent phase II and III clinical
      trials demonstrate that trastuzumab is active against breast tumors, both as a
      single agent and in combination with chemotherapy. In patients with HER2
      overexpressing metastatic breast cancer, use of trastuzumab in combination with
      chemotherapy is associated with a 20% reduction in relative risk of death and an
      increase in median survival from 20.3 to 25.1 months compared to chemotherapy
      alone. Side effects include fever and chills and an unexpected increase in
      doxorubicin/trastuzumab-associated cardiomyopathy. Clinical development is now
      focused on trastuzumab in combination with chemotherapy regimens that do not
      contain an anthracycline. Trastuzumab in combination with docetaxel is
      synergistic in vitro. Data from ongoing clinical trials are consistent with this
      finding. Preliminary data from 3 phase II studies suggest a 44%-63% response rate
      when the combination is used first or second line in HER2-overexpressing
      metastatic breast cancer. The combination of docetaxel with trastuzumab is well
      tolerated and has not been associated with significant cardiotoxicity. Given in
      vitro evidence that platinum salts act synergistically with trastuzumab and
      docetaxel, and phase II data suggesting clinical efficacy and good tolerability,
      the combination of platinum salt plus trastuzumab and docetaxel is now being
      assessed in adjuvant trials

PMID- 11970741
TI  - Present state and future prospects: a review of cooperative groups' adjuvant and
      neoadjuvant trials in breast cancer.
AB  - In patients with operable breast cancer, adjuvant hormonal therapy and adjuvant
      chemotherapy result in significant and long-term reductions in the rates of
      disease recurrence and death. These reductions are evident in both patients with
      node-negative as well as in those with node-positive disease. However, several
      issues in the adjuvant treatment of breast cancer still remain unresolved. These
      issues were recently considered at the 2000 National Institutes of Health (NIH)
      Consensus Development Conference, which reviewed the current state of knowledge
      on adjuvant therapy and outlined strategies for future research. In the area of
      adjuvant hormonal therapy, tamoxifen is still the gold standard, and present
      evidence supports the use of tamoxifen for patients with estrogen receptor (ER)
      positive tumors irrespective of age, menopausal status, nodal status, or tumor
      size. Optimal duration of tamoxifen therapy is about 5 years. Future research
      directions include evaluating the benefit of extending tamoxifen beyond 5 years,
      the contribution of ovarian ablation, and the role of hormonal manipulations
      involving selective ER modulators and aromatase inhibitors instead of or in
      addition to tamoxifen. In the area of adjuvant chemotherapy, polychemotherapy
      regimens have been consistently found to be superior to single agents, and
      anthracycline-containing regimens produce a small but statistically significant
      improvement in survival when compared with regimens not containing an
      anthracycline. High-dose adjuvant chemotherapy with stem cell support has not
      been proven superior to standard regimens. Neoadjuvant therapy offers the
      possibility of testing in vivo the sensitivity of individual tumors to particular
      cytotoxic regimens and, hence, of improving ultimate disease control, as well as
      reducing the extent of local therapy. The contribution and optimal integration of
      taxanes in the adjuvant setting are yet to be established but are the subject of
      intense research effort. Similarly, novel targeted therapies such as trastuzumab
      and bisphosphonates are currently being evaluated in adjuvant studies

PMID- 11970742
TI  - Primary (neoadjuvant) chemotherapy with docetaxel in breast cancer.
AB  - The use of primary or neoadjuvant chemotherapy for locally advanced breast
      cancer, including those patients with inflammatory breast cancer, is well
      established. The use of primary chemotherapy has also been investigated in
      patients with operable breast cancer. The potential benefit of using primary
      chemotherapy is the opportunity to administer systemic therapy at an earlier
      timepoint, where it may be more effective against microscopic disease. In
      addition, primary chemotherapy for patients with operable breast cancer may also
      result in higher rates of breast conservation, axillary nodal downstaging, and
      potential improvement in patient outcome. A variety of different chemotherapy
      drugs have been evaluated in the primary chemotherapy setting. One of the most
      common approaches is to use an anthracycline-based regimen for 4 or more cycles
      of treatment before considering definitive local therapy. Although high tumor
      response rates have been reported using anthracycline-based regimens, the
      fraction of patients actually attaining a pathologic complete response has
      remained small (less than 20%). With the introduction of new chemotherapy drugs,
      such as docetaxel, which is associated with a very high tumor response rate in
      metastatic disease, a natural evolution of clinical investigation is to use
      docetaxel in the neoadjuvant or primary chemotherapy setting. Some of the recent
      trials that have evaluated single-agent docetaxel, docetaxel-based chemotherapy
      combinations, and novel sequencing strategies that include docetaxel in the
      neoadjuvant setting are reviewed. The results from these trials clearly suggest
      that docetaxel-containing treatment strategies can be considered a standard in
      the primary chemotherapy setting

PMID- 11970744
TI  - Exemestane improves survival in metastatic breast cancer: results of a phase III
      randomized study.
AB  - We compared the efficacy and safety of the oral aromatase inactivator exemestane
      (EXE) with megestrol acetate (MA) in women with metastatic breast cancer. This
      phase III randomized, double-blind, multicenter study was conducted in 769
      postmenopausal women who had experienced tamoxifen failure. Treatment arms
      consisted of EXE 25 mg once daily (n=366) or MA 40 mg four times daily (160 mg
      daily; n=403). Peer-reviewed, intent-to-treat analyses demonstrated that EXE
      induced a trend toward higher rates of complete response (CR)+partial response
      (PR) (15.0% vs. 12.4%) and of CR+PR+stable disease (SD)=24 weeks (37.4% vs.
      34.6%), but differences were not statistically significant. Statistically
      significant differences favoring EXE were seen in median duration of CR+PR+SD=24
      weeks (60.1 vs. 49.1 weeks; P=0.025), time to tumor progression (20.3 vs. 16.6
      weeks; P=0.037), time to treatment failure (16.3 vs. 15.7 weeks; P=0.042), and
      overall survival (not reached vs. 123.4 weeks; P=0.039). Both treatments were
      well tolerated, but MA was associated with more grade 3 or 4 weight gain (8% vs.
      17%, P=0.001); the pain score was sim-ilar in both groups. There was a trend
      toward superiority in treatment-related signs and symptoms (TRSS) with EXE. There
      was greater improvement in the pain score and TRSS in patients achieving an
      objective response with EXE vs. MA. Quality of life improved or was similar for
      EXE in most domains. Exemestane offers an important new treatment option for
      postmenopausal women with hormone-responsive breast cancer.

PMID- 11970745
TI  - Promising results with exemestane in the first-line treatment of metastatic
      breast cancer: a randomized phase II EORTC trial with a tamoxifen control.
AB  - Because tamoxifen (TAM), a nonsteroidal antiestrogen, is routinely used in the
      adjuvant setting, other hormone therapies are needed as alternatives for first
      line treatment of metastatic breast cancer (MBC). Currently, exemestane (EXE) and
      other antiaromatase agents are indicated for use in patients who experience
      failure of TAM. In this multicenter, randomized, open-label, TAM-controlled (20
      mg/day), phase II trial, we examined the activity and tolerability of EXE 25
      mg/day for the first-line treatment of MBC in postmenopausal women. Exemestane
      was well tolerated and demonstrated substantial first-line antitumor activity
      based on intent-to-treat analysis of peer-reviewed responses. In the EXE arm,
      values for complete, partial, and objective response, clinical benefit, and time
      to tumor progression (TTP) exceeded those reported for TAM although no
      statistical comparison was made. Based on these encouraging results, a phase III
      trial will compare EXE and TAM.

PMID- 11970746
TI  - Antiaromatase agents after adjuvant tamoxifen: rationale and clinical
      implications.
AB  - Although tamoxifen is considered standard adjuvant hormonal therapy in receptor
      positive, stage I and II breast cancer, information on its optimal duration of
      administration has only been reported recently and, for many, the subject is
      still a matter of scientific debate. Data suggest that there is a time period
      beyond which, if tamoxifen is continued, it may become ineffective or even
      detrimental to the patient. Tamoxifen is usually discontinued after approximately
      5 years of therapy, at which time most patients are thought to be disease free;
      however, some patients may harbor residual micrometastases. A fraction of these
      patients will have micrometastatic tumor cells that are still responsive to
      tamoxifen, and tamoxifen discontinuation could result in cancer cell growth. The
      preponderance of clinical data, however, indicate that a greater fraction of
      patients will have micrometastatic tumor cells that have become progressively
      resistant to tamoxifen. In fact, tumor cell growth could be stimulated by
      continued therapy with the drug. Although in some patients the micrometastatic
      tumor cells may have become hormonally unresponsive, in most cases (tamoxifen
      responsive or tamoxifen-stimulated micrometastases), the tumor remains hormonally
      responsive. Therefore, the use of anti-aromatase agents to reduce the level of
      estrogenic stimulation and, as a result, the risk of recurrence may prove to be a
      valuable approach at the time of tamoxifen discontinuation. The National Surgical
      Adjuvant Breast and Bowel Project (NSABP) is in the final stages of developing a
      clinical trial (NSABP B-33) to evaluate the effect of administering 2 years of
      therapy with the aromatase inactivator exemestane to postmenopausal, receptor
      positive patients who have completed 5 years of tamoxifen therapy and are disease
      free at the time of tamoxifen discontinuation.

PMID- 11970747
TI  - Exemestane in breast cancer: current status and future directions.
AB  - Exemestane is a novel, potent, and specific third-generation aromatase
      inactivator developed for breast can-cer therapy. The drug is effective in
      patients with metastatic disease failing tamoxifen alone or tamoxifen followed by
      megestrol acetate or a nonsteroidal aromatase inhibitor. In a phase III study,
      exemestane was superior to megestrol acetate in overall survival, time to tumor
      progression, and time to treatment failure in women with metastatic disease who
      experienced failure of tamoxifen. Preliminary evidence suggests activity to
      exemestane exceeds that obtained with tamoxifen as first-line treatment. Two
      studies are comparing sequential treatment with tamoxifen followed by exemestane
      to tamoxifen monotherapy in the adjuvant setting. A third study is comparing the
      toxicity profile of exemestane with that of placebo in patients with early breast
      cancer who are at low risk of relapse. The findings from these studies will
      determine the role of exemestane in early breast cancer and lay the foundation
      for assessing its potential role in breast cancer prevention.

PMID- 11970748
TI  - Rationale and use of epirubicin-based therapy in the adjuvant setting.
AB  - The taxanes paclitaxel and docetaxel have an important role in the treatment of
      breast cancer, and numerous randomized trials have evaluated their efficacy for
      this indication. A systematic, evidence-based review was performed, which
      included all randomized, controlled trials evaluating taxanes for the treatment
      of early- or advanced-stage breast cancer that were identified in CANCERLIT and
      MEDLINE searches. The primary objectives of this review were to determine the
      dose and schedule for each taxane that was associated with the most favorable
      therapeutic index, and to determine whether (and under what circumstances) the
      taxanes improved survival. The search revealed 18 randomized phase II (n=1) or
      phase III (n=17) trials. For metastatic breast cancer, the dose and schedule
      associated with the most favorable therapeutic index for paclitaxel was 175 mg/m2
      given as a 3-hour infusion every 3 weeks, and docetaxel was 60-100 mg/m2 given as
      a 1-hour infusion every 3 weeks. Survival was improved under the following
      circumstances: (1) when 4 cycles of paclitaxel (175 mg/m2 every 3 weeks) was
      given following 4 cycles of conventional doxorubicin- cyclophosphamide for
      axillary node-positive operable breast cancer, (2) when trastuzumab was added to
      paclitaxel as first-line therapy for metastatic breast cancer that overexpressed
      HER2/neu, and (3) when docetaxel was given as second-line therapy for
      anthracycline-resistant disease. Although a survival benefit was found for
      taxanes as a component of first-line therapy in two of six trials, the
      interpretation of both positive trials was confounded by a lack of crossover to
      taxane therapy in those who were initially randomized to receive standard
      therapy. The taxanes improve survival in patients with early-stage breast cancer
      and selected patients with metastatic breast cancer. Further research is
      necessary in order to identify the efficacy of docetaxel relative to paclitaxel,
      the optimal dose of docetaxel, the role of weekly taxane therapy, the role of
      trastuzumab plus taxanes in early-stage disease, and whether taxanes are more
      effective when given concomitantly or sequentially in patients with early-stage
      disease

PMID- 11970749
TI  - Role of epirubicin in advanced breast cancer.
AB  - Anthracyclines were first introduced for the treatment of metastatic breast
      cancer in the 1970s and are still among the most active single agents for the
      treatment of this disease. Unfortunately, their clinical value is limited by late
      onset ventricular dysfunction. Epirubicin, an anthracycline analogue, does not
      eliminate the risk of cardiotoxicity but is less cardiotoxic and myelotoxic than
      doxorubicin at equimolar doses, thereby allowing the safe administration of
      cumulative doses between 950 and 1000 mg/m2. The inclusion of epirubicin in
      combination regimens, such as fluorouracil/epirubicin/cyclophosphamide (FEC), has
      been shown to be safe and active as first-line treatment for metastatic breast
      cancer. In the past few years, new drugs, including taxanes, have shown a high
      level of activity as single agents in the treatment of advanced breast cancer.
      Doxorubicin/paclitaxel combinations have shown high overall response rates (90%)
      as first-line chemotherapy of advanced breast cancer; however, congestive heart
      failure has been reported in up to 20% of patients. Epirubicin/paclitaxel
      combinations have been associated with grade 3 cardiotoxicity (6%) in only one
      study. We report findings of a trial of combination epirubicin/paclitaxel as
      first-line treatment of advanced breast cancer, with overall response rates
      (ORRs) of 84% and a complete response (CR) rate of 19%. Achieving a CR to first
      line chemotherapy for advanced breast cancer appears to predict survival, and
      adding an active drug with a different mechanism of action and nonoverlapping
      toxicity might increase the percentage of CRs. We therefore tested the
      feasibility and activity of 6 to 8 courses of first-line treatment with a three
      drug combination (gemcitabine 1000 mg/m2 days 1 and 4, epirubicin 90 mg/m2 day 1,
      and paclitaxel 175 mg/ m2 over 3 hours on day 1) in a phase II study of 36
      metastatic breast cancer patients. Treatment was well tolerated, with an ORR of
      92% (95% confidence interval: 77.53%-98.25%) and a CR of 31%. In considering
      retreating patients who progress or relapse after receiving an anthracycline
      /taxane-containing regimen with the same active drugs, epirubicin appears ideal
      in both the adjuvant and metastatic breast cancer settings.

PMID- 11970750
TI  - Rationale and design of a phase III trial of adjuvant sequential epirubicin/
      cyclophosphamide and taxane versus concurrent epirubicin/taxane in operable node
      positive breast cancer.
AB  - The sequential use of a doxorubicin combination followed by paclitaxel has been
      reported to improve disease-free and overall survival in patients with node
      positive breast cancer beyond that obtained with doxorubicin/cyclophosphamide
      combinations. Epirubicin is associated with less cardiotoxicity than doxorubicin
      and can be used at cumulative dose levels or intensities that cannot be safely
      achieved with doxorubicin. Epirubicin/taxane combinations have exhibited
      significant activity when used in the treatment of metastatic breast cancer.
      Based on these safety and efficacy data, a phase III adjuvant trial will compare
      the efficacy of a concurrent epirubicin/taxane regimen with sequential
      epirubicin/cyclophosphamide followed by taxane treatment in patients with
      operable node-positive breast cancer.

PMID- 11970751
TI  - Selection criteria for epirubicin-based adjuvant chemotherapy in node-negative
      breast cancer.
AB  - The management of node-negative breast cancer is problematic due to the lack of
      reliable prognostic para-meters that distinguish patients who benefit from
      adjuvant chemotherapy. Since surgery alone is curative in approximately 70% of
      these patients, clinicians are faced with the dilemma of possible overtreatment
      or undertreatment. As a compromise, traditional
      cyclophosphamide/methotrexate/fluorouracil (CMF) is administered rather than
      newer, potentially more effective regimens containing anthracyclines or taxanes.
      Invasion and metastasis of solid tumors require tumor-biologic factors that
      promote the dissolution of the surrounding tumor matrix and the basement
      membranes, and the serine protease urokinase-type plasminogen activator (uPA) and
      its inhibitor, plasminogen activator-inhibitor type 1 (PAI-1), play major roles
      in these invasive processes. Our laboratory and others have reported that
      determinations by enzyme-linked immunosorbent assay (ELISA) of uPA and PAI-1
      concentrations in tumor tissue extracts reliably separate patients with node
      negative breast cancer at very low risk of relapse even without chemotherapy from
      high-risk patients who urgently need intensive effective treatment in order to
      reduce increased mortality. By eliminating low-risk patients from study entry,
      these markers permit unbiased evaluation of newer anthracycline-containing
      regimens in high-risk patients with node-negative disease. A multicenter,
      transnational European study is currently underway to compare the efficacy of a
      regimen combining epirubicin and cyclophosphamide with the traditional CMF
      regimen in these patients, whose risk of relapse and death is similar to that of
      many patients with node-positive disease.

PMID- 11970752
TI  - Epirubicin in breast cancer: present and future.
AB  - Epirubicin, a member of the anthracycline family of chemotherapeutic agents, has
      been widely used throughout the world both as adjuvant therapy in early breast
      cancer and in metastatic breast cancer. Clinical trials with epirubicin have
      examined the importance of a dose-response relationship, therapeutic dose, and
      optimum duration of chemotherapy. In addition, pharmacokinetic studies have
      provided data on ideal combinations with other agents. Epirubicin-containing
      regimens are considered to be superior to those containing cyclophosphamide,
      methotrexate, and fluorouracil (CMF) and are also used in patients with locally
      advanced stage IIIA/IIIB breast cancer. Combinations with other chemotherapeutic
      agents (eg, epirubicin plus a taxane, sequential or combined use of these agents)
      are being evaluated in ongoing clinical trials. Moreover, recent studies have
      suggested that biologic markers, such as tumor HER2/neu overexpression, predict
      responses to dose-intensive anthracycline chemotherapy, and combinations with
      nonchemotherapeutic regimens (eg, trastuzumab) may provide additional benefits,
      but such strategies require further evaluation.

PMID- 11970753
TI  - Comparison of in vitro exemestane activity versus other antiaromatase agents.
AB  - Anastrozole, letrozole, and exemestane are the most selective and potent oral
      antiaromatase agents currently available. However, in vitro and in vivo studies
      comparing these agents are lacking. Anastrozole and letrozole are reversible,
      competitive nonsteroidal type II inhibitors, whereas exemestane is an
      irreversible steroidal type I inactivator. The study was conducted to determine
      the impact of this characteristic on in vitro residual aromatase activity and
      protein levels after incubation of JEG-3 cells with aminoglutethimide (a type II
      inhibitor), anastrozole, exemestane, or letrozole. Aromatase activity was
      measured after various incubation times with each antiaromatase agent at a
      concentration 10 times higher than IC50 (concentration giving 50% inhibition).
      Only exemestane induced a residual inhibition of aromatase activity after its
      removal, without any change in the aromatase protein level. Aromatase activity
      increased after preincubation of JEG-3 cells with either aminoglutethimide or
      anastrozole without any change in the aromatase protein level. The aromatase
      protein level increased rapidly when cells were incubated with letrozole and
      aromatase activity inhibition disappeared immediately after removal of the drug.
      The breakthrough effects in aromatase activity or protein levels observed after
      treatment with reversible inhibitors may be a factor in therapeutic failure with
      these agents. These results suggest a possible advantage for exemestane because
      it is the only clinically available oral irreversible aromatase inactivator.

PMID- 11970754
TI  - Treating breast precancer.
AB  - Recent studies strongly support the theory that breast precancers such as
      atypical hyperplasia (AH) and ductal carcinoma in situ (DCIS) are closely related
      to the development of invasive breast cancer. There is growing belief that
      reduction in the burden of breast intraepithelial neoplasia (IEN) through
      intervention may translate into a decreased burden of invasive cancer. Current
      research is focusing on two issues. First, improved modalities for detecting
      precancers are needed; breast epithelial cell analysis appears particularly
      promising. Second, clinical trials are needed that would permit rapid evaluation
      of agents that can reduce breast cancer risk. Results of the few available trials
      suggest that several agents may effectively reduce the burden of breast
      precancer.

PMID- 11970755
TI  - The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis and
      early clinical development of VEGF-receptor kinase inhibitors.
AB  - Angiogenesis, or the formation of new blood vessels from preexisting vasculature,
      plays a major role in tumor growth and metastasis formation. Therefore,
      inhibiting tumor angiogenesis may be a promising therapeutic strategy. Paracrine
      stimuli from tumor cells are the main promoters of angiogenesis. They activate
      endothelial cells to proliferate and migrate, subsequently resulting in new tube
      formation and blood flow. This complex process involves numerous biological
      activities. Vascular endothelial growth factor (VEGF) is a potent and specific
      angiogenic factor. Originally identified for its ability to induce vascular
      permeability and stimulate endothelial cell growth, VEGF is now known to be a key
      requirement for tumor growth. Currently, three high-affinity tyrosine kinase
      receptors for VEGF have been identified, of which VEGF receptor (VEGFR)-Flk-1/KDR
      (VEGFR-2) is exclusively expressed in vascular endothelial cells. Because the
      VEGFR-2 system is a dominant signal-transduction pathway in regulating tumor
      angiogenesis, specific inhibitors of this pathway inhibit metastases, microvessel
      formation, and tumor-cell proliferation. Induction of apoptosis in tumor cells
      and endothelial cells has also been observed. The clinical importance of VEGF for
      tumor growth is supported by the fact that most tumors produce VEGF and that the
      inhibition of VEGF-induced angiogenesis significantly inhibits tumor growth in
      vivo. In this review, we discuss the biologic role of VEGF and the therapeutic
      options for inhibiting VEGF in cancer patients.

PMID- 11970756
TI  - Antiaromatase agents: preclinical data and neoadjuvant therapy.
AB  - Novel drugs such as exemestane are highly potent and specific inactivators of
      aromatase activity in test systems such as placental microsomes, breast cancer
      homogenates, and cultures of mammary fibroblasts, with IC50 values in the nmol
      range. When given in daily milligram amounts to postmenopausal women, exemestane
      almost totally blocks peripheral aromatase and reduces circulating estrogens to
      levels that are at the limit of detection of current assays. Additionally,
      exemestane profoundly inhibits in situ aromatase activity both in breast cancers
      and surrounding nonmalignant breast. In postmenopausal women with large estrogen
      receptor-rich cancers, these endocrine influences translate into antitumor
      effects, and, for example, following exemestane treatment in the neoadjuvant
      setting, tumor resolution may be observed on mammography. In conclusion, the
      ability to block estrogen biosynthesis peripherally and locally within the breast
      provides new options for the treatment of hormone-sensitive breast cancers in
      postmenopausal women

PMID- 11970757
TI  - Classification and treatment of lymphomas.

PMID- 11970758
TI  - 43rd Annual Meeting of the American Society of Hematology, December 7-11, 2001,
      Orlando, Florida.

PMID- 11970759
TI  - Iodine-131 Tositumomab(Bexxar) in relapsed/refractory non-Hodgkin's lymphoma:
      update from the 2001 American Society of Hematology meeting.

PMID- 11970760
TI  - Stem cell transplantation for Hodgkin's disease: a review of the literature.
AB  - High-dose chemotherapy followed by autologous peripheral-blood stem cell
      transplantation has resulted in long-term disease-free survival of 30%-60% in
      selected patients with refractory and relapsed Hodgkin's disease. In addition, a
      significant reduction in early transplant-related mortality in more recent
      studies has led to the widespread acceptance of autografting. Comparatively few
      studies of allografting for Hodgkin's disease have been performed. Although no
      prospective randomized trials have been performed, historical results show a
      significantly lower relapse rate when allografting results are compared to
      autografting results. These results suggest that a graft-versus-Hodgkin's disease
      effect may exist. Unfortunately, the lower relapse rate following allografting is
      offset by higher transplant-related mortality. The use of low-intensity
      nonmyeloablative regimens for allografting may harness a graft-versus-Hodgkin's
      disease effect with less morbidity and mortality than that observed following
      conventional allografting.

PMID- 11970761
TI  - Quality-of-life improvements in cutaneous T-cell lymphoma patients treated with
      denileukin diftitox (ONTAK).
AB  - Cutaneous T-cell lymphoma (CTCL) can be associated with painful, pruritic,
      disfiguring lesions. As part of a multicenter, randomized phase III trial in
      patients with heavily pretreated advanced and/or recurrent CTCL, the effects of
      an interleukin-2 receptor-targeted fusion protein, denileukin diftitox (DAB389IL
      2, ONTAK), on patient-rated overall quality of life (QOL), skin appearance, and
      pruritus severity were evaluated. A total of 71 patients with stage IB-IVA CTCL
      received intravenous denileukin diftitox 9 microg/kg/day or 18 microg/kg/day over
      15-60 minutes for 5 consecutive days on an outpatient basis; cycles were planned
      for every 21 days for a total of 8 cycles over 6 months. Prior to each treatment
      cycle, patients were evaluated for disease response and were asked to self-rate
      their overall QOL via the Functional Assessment of Cancer Therapy-General (FACT
      G) questionnaire, skin appearance (7-point scale), and pruritus severity (10-cm
      visual analogue scale). Composite FACT-G and most individual subscale scores
      (physical, social/family, emotional, and functional well being) in documented
      responders (n = 21) gradually increased during the study period, generally
      reaching statistical significance (P < 0.05) by cycle 3, and were significantly
      (P < or = 0.041) higher than the scores of nonresponders at endpoint.
      Additionally for responders, assessments of skin severity and pruritus severity
      showed significant (P < or = 0.05) improvements at study endpoint compared with
      baseline. Adverse transfusion-related events (eg, hypersensitivity reactions, flu
      like syndrome) were common during cycles 1 and 2, and vascular-leak syndrome
      occurred in 25% of patients. Denileukin diftitox was not associated with any
      clinically significant myelosuppression. Heavily pretreated patients with
      advanced and/or recurrent CTCL who responded to denileukin diftitox therapy
      showed significant improvements in self-rated overall QOL, skin appearance, and
      pruritus severity.

PMID- 11970762
TI  - Efficacy of fludarabine/mitoxantrone/dexamethasone alternating with CHOP in bulky
      follicular non-Hodgkin's lymphoma.
AB  - This phase II study investigated the efficacy of alternating
      fludarabine/mitoxantrone/ dexamethasone (FMD) with
      cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) chemotherapy for
      patients with high tumor burden, follicular non-Hodgkin's lymphoma. Maintenance
      interferon was given in a nonrandomized fashion, and a retrospective analysis of
      its impact was performed. A total of 87 patients were included (44 females and 43
      males). The median age of patients was 56 years (range, 25-86 years). All
      patients had high tumor burden as defined by the Groupe d'Etude des Lymphomes
      Folliculaires (GELF) criteria. Eighty-four percent of patients (73/87) had stage
      III/IV disease and 99% of patients (86/87) had good performance status. The
      majority of patients had not been previously treated, with only 3 patients
      receiving prior oral alkylators or cyclophosphamide/vincristine/prednisone (COP).
      A total of 637 cycles of FMD/CHOP were administered and were well tolerated
      during this trial, the majority on an outpatient basis. The overall response rate
      was 95% (79 complete response/ unconfirmed complete response/partial response) in
      the 83 evaluable patients. Event-free survival (EFS) was 28.7 months, with time
      to progression (TTP) at 29 months and time to treatment failure at 41 months.
      Overall survival was not reached. Patients had similar EFS and TTP as patients in
      the French GELF trial with a shorter duration of chemotherapy. Patients with a
      lower International Prognostic Index (IPI) score had better EFS when compared to
      those with a higher IPI score (median EFS not reached versus 22.6 months). Serum
      beta2-microglobulin levels were not a significant predictive factor. An informal
      analysis of interferon maintenance therapy suggests that patients who tolerated
      the immune modifier did better than those who did not. Alternating FMD/CHOP is a
      feasible and effective therapeutic option for patients with high tumor burden,
      low-grade non-Hodgkin's lymphoma. While this regimen may not offer dramatic
      benefit over FMD alone, it is beneficial in those patients for whom a prompt
      treatment response is needed.

PMID- 11970763
TI  - Testicular lymphoma: a literature review and report of a case with a zoster-like
      cutaneous recurrence.
AB  - Testicular lymphoma accounts for approximately 1% of all cases of non-Hodgkin's
      lymphoma. This distinct clinical entity can have an aggressive course with a high
      rate of systemic relapse. We describe a unique case of a diffuse large B-cell
      lymphoma, T-cell-rich variant with cutaneous dermatomal zosteriform recurrence
      presenting as neuralgia. This case represents a unique pattern of treatment
      failure in this aggressive extranodal lymphoma.

PMID- 11970764
TI  - Noninvasive detection of multidrug resistance in patients with hematological
      malignancies: are we there yet?
AB  - The success of chemotherapy in the treatment of malignancies may be limited by
      cellular mechanisms leading to drug resistance. In hematological malignancies,
      mechanisms leading to the development of multidrug resistance (MDR) include
      overexpression of the membrane-based export pump P-glycoprotein (Pgp) and the MDR
      associated protein (MRP). Recently, the overexpression of the lung-resistance
      protein (LRP) has also been associated with reduced intracellular drug
      accumulation. A major problem in assessing the significance of the expression of
      these resistance proteins in clinical MDR has been the variability of detection
      techniques either at the mRNA or protein level. Currently, the detection of
      resistance proteins relies heavily on antibody and cDNA probes, and these methods
      may not be informative about the in vivo function of Pgp, MRP, or LRP. Nuclear
      medicine imaging techniques such as single-photon emission tomography (SPECT) and
      positron emission tomography (PET) have been evaluated for noninvasive
      determination of the presence and the function of Pgp- and MRP-mediated transport
      systems. Technetium 99m ((99m)Tc)-sestamibi, an agent in clinical use for
      myocardial perfusion and tumor imaging, is recognized as a substrate for Pgp and
      MRP, and has been used to visualize Pgp expression. (99m)Tc-tetrofosmin is also a
      substrate for the Pgp efflux pump mechanism and is used to evaluate Pgp function
      in in vitro and in vivo studies. Recently, radiopharmaceuticals including carbon
      11-labeled colchicine, verapamil, and daunorubicin have been used in cell line
      and animal studies for the evaluation of Pgp-mediated transport functions using
      PET technology. Preliminary results suggest that the potential to detect MDR in
      tumors prior to or after exposure to chemotherapeutic agents exists in imaging
      using either (99m)Tc-labeled compounds and SPECT or positron emitting compounds
      and PET.

PMID- 11970765
TI  - Antibody therapy in acute myeloid leukemia: current status and future directions.
AB  - Monoclonal antibodies have become an important modality for cancer therapy. The
      genetically engineered, humanized anti-CD33 antibody HuM195 has demonstrated
      modest activity against overt relapsed acute myeloid leukemia (AML) and more
      substantial activity against minimal residual disease in acute promyelocytic
      leukemia. Radioimmunotherpay with beta-particle-emitting isotopes has eliminated
      large leukemic burdens while minimizing radiation exposure to normal tissues in
      both nonmyeloablative and myeloablative regimens. Targeted beta-particle
      immunotherapy with agents such as bismuth 213-labeled HuM195 offers the
      possibility of a more selective tumor cell kill with less damage to surrounding
      normal cells. Directed chemotherapy using the anti-CD33-calicheamicin conjugate
      gemtuzumab ozogamicin (Mylotarg) has produced remissions in patients with
      relapsed AML.

PMID- 11970766
TI  - Early phase I/II trials with gemtuzumab ozogamicin (Mylotarg) in acute myeloid
      leukemia.
AB  - Relapsed acute myeloid leukemia (AML) carries a poor prognosis. Treatment options
      are limited, and their toxicities are substantial. There is an urgent need for
      novel therapies that are effective and have acceptable side effects. Gemtuzumab
      ozogamicin (Mylotarg) is an immunoconjugate targeted against CD33, which is
      expressed on more than 90% of myeloid leukemic blasts. The antibody is attached
      to calicheamicin, a potent cytotoxic enediyne antibiotic that inhibits DNA
      synthesis and induces apoptosis. In vitro studies showed excellent activity of
      gemtuzumab ozogamicin in leukemic cell lines and encouraged the evaluation of
      this agent in patients. In this review, early phase I/II studies that led to the
      US Food and Drug Administration approval of this immunoconjugate for older
      patients with relapsed AML are discussed. Potential adverse events reported with
      this agent, particularly the recent data of possible veno-occlusive disease and
      increased hepatotoxicity, are addressed. This agent is currently being
      investigated in many clinical trials as a front-line approach in previously
      untreated individuals, and it is likely that it will have many more indications
      in the near future.

PMID- 11970767
TI  - Trials with gemtuzumab ozogamicin (Mylotarg) combined with chemotherapy regimens
      in acute myeloid leukemia.
AB  - Gemtuzumab ozogamicin (Mylotarg) is an immunoconjugate composed of a recombinant
      humanized murine anti-CD33 antibody linked to calicheamicin, a potent cytotoxic
      agent. The aim of this review is to summarize ongoing trials with gemtuzumab
      ozogamicin in combination with chemotherapy in acute myeloid leukemia (AML)
      patients. The studies include determination of safety and efficacy of gemtuzumab
      ozogamicin in combination with chemotherapy in previously untreated as well as
      relapsed and refractory AML patients. These studies also determine gemtuzumab
      ozogamicin's activity in patients with other CD33+ neoplastic diseases such as
      myelodysplastic syndrome, acute promyelocytic leukemia, chronic myeloid leukemia,
      and certain subsets of acute lymphocytic leukemia. Moreover, trials are exploring
      the use of gemtuzumab ozogamicin with novel targeted agents such as Bcl-2
      antisense molecules. Gemtuzumab ozogamicin is associated with an acceptable
      toxicity profile as a single agent; however, the incidence of veno-occlusive
      disease remains a concern with the use of gemtuzumab ozogamicin in combination
      with chemotherapy.

PMID- 11970768
TI  - Acute and long-term toxicities associated with gemtuzumab ozogamicin (Mylotarg)
      therapy of acute myeloid leukemia.
AB  - Gemtuzumab ozogamicin (Mylotarg) targets leukemia cells that express CD33 by
      means of a humanized anti-CD33 monoclonal antibody conjugated to a modified
      antitumor antibiotic, calicheamicin. The effects of gemtuzumab ozogamicin (given
      intravenously at a dose of 9 mg/m2 for 2 doses separated by 2 weeks) have been
      evaluated in 3 phase II studies involving patients (n = 188) with acute myeloid
      leukemia (AML) in first relapse. Interim analysis has revealed that 30% of
      patients achieved remission, characterized by < or = 5% blasts in the marrow,
      neutrophil count > or = 1500/microL, hemoglobin > or = 9 g/dL, and independence
      from red blood cell and platelet transfusion. Grade 3/4 acute toxicities included
      nausea or vomiting (11%); elevated serum aminotransferase enzyme (16%) and
      bilirubin (26%) levels; and infusion-related chills (9%), fever (6%), and
      hypotension (5%). As predicted with CD33-targeted therapy, most patients had
      neutropenia (98%) and thrombocytopenia (99%). However, the incidence of grade 3/4
      bleeding events (14%) and infection rates (pneumonia, 7%; sepsis, 15%) was low.
      No patients were reported to have treatment-related cardiotoxicity, cerebellar
      toxicity, or alopecia. Veno-occlusive disease (VOD) after gemtuzumab ozogamicin
      treatment (but prior to other therapies) occurred in 2% of patients (4/188), and
      the VOD-related death rate was < 1% (1/188). Prior hematopoietic stem cell
      transplant may be a risk factor for VOD (P = 0.002, univariate analysis).
      Gemtuzumab ozogamicin is a safe and effective treatment in carefully selected
      patients with AML in first relapse.

PMID- 11970769
TI  - Management of hepatic sinusoidal obstruction syndrome following treatment with
      gemtuzumab ozogamicin (Mylotarg).
AB  - Gemtuzumab ozogamicin (Mylotarg) therapy may cause sinusoidal obstruction
      syndrome (SOS), the mechanism of which probably involves targeting of CD33+ cells
      in the sinusoids of the liver, activation of stellate cells, damage to sinusoidal
      endothelial cells, sinusoidal vasoconstriction, and ischemic hepatocyte necrosis.
      The clinical manifestations of this liver injury are hepatomegaly, weight gain,
      ascites, jaundice, and elevation of serum aminotransferase enzymes. An approach
      to patient management includes being certain that SOS is the correct diagnosis;
      ensuring that liver blood flow is optimized; and managing the accumulation of
      fluid in the peritoneal cavity, pleural spaces, and pulmonary interstitium.
      Currently, there is no specific therapy that is directed at the sinusoidal
      pathology caused by gemtuzumab ozogamicin. There are, however, several rational
      therapies that might be tried in patients who exhibit adverse prognostic signs
      early in the course of SOS. There is also considerable ongoing hepatology
      research dealing with stellate cell and sinusoidal endothelial cell biology and
      regulation of sinusoidal blood flow that can be brought to bear on this problem
      in the future.

PMID- 11970770
TI  - CD33 as a target for selective ablation of acute myeloid leukemia.
AB  - The CD33 antigen is a 67-kd glycosylated transmembrane protein of the sialic acid
      binding immunoglobulinlike lectin (siglec) family with immunoreceptor tyrosine
      based inhibitory motifs. It is expressed on the surface of normal mature and
      immature myeloid cells, including colony-forming progenitor cells, and on
      leukemic blasts from the majority of patients with acute myeloid leukemia (AML).
      CD33 is not expressed by the normal stem cells, suggesting that in vivo ablation
      of CD33-bearing normal and leukemic myeloid cells might lead to the establishment
      of normal hematopoiesis by the remaining normal stem cells. However, whether
      there are significant numbers of CD33- leukemic stem cells is controversial.
      Therapeutic trials using unmodified anti-CD33 antibodies have, thus far, met with
      limited success. Studies with a radiolabeled anti-CD33 antibody have demonstrated
      rapid saturation of, and internalization by, leukemic blast cells after
      intravenous administration, suggesting the possibility of using an anti-CD33
      antibody to deliver a cytotoxic drug. Using gemtuzumab ozogamicin (Mylotarg, a
      humanized anti-CD33 antibody conjugated with calicheamicin, the effectiveness of
      in vivo ablation of CD33+ cells to treat patients with AML was borne out by the
      portion of patients who achieved remission. To what extent CD33- leukemic
      precursors are responsible for failure to respond or for relapse following
      gemtuzumab ozogamicin therapy remains to be determined.

PMID- 11970771
TI  - A genealogy of the social identity tradition: Deleuze and Guattari and social
      psychology.
AB  - This paper explores how social psychology has theorized the relationship between
      the individual and society. This is done through a genealogical analysis of the
      Social Identity Tradition (SIT). It is argued that the current state of SIT is
      profoundly shaped by a range of intellectual and moral strategies derived from
      the work of Henri Tajfel. This 'Tajfel effect' manifests itself as a way of
      settling theoretical, practical and moral disputes through the invocation of
      Tajfel as a founding figure. However, this strategy also ties SIT into a model of
      the subject and an understanding of society that is increasingly seen as
      problematic. The paper then goes on to show how a range of core concepts at the
      heart of SIT may be usefully reformulated by drawing on the work of Deleuze and
      Guattari. Their work offers SIT a way of thinking about individuals and groups as
      sites for connection and differentiation. This is illustrated using the example
      of Nazi social relations that was originally deployed by Tajfel. Potential issues
      and direction for SIT as reinvigorated by the encounter with Deleuze and Guattari
      are then sketched out.

PMID- 11970772
TI  - Psychological need-satisfaction and subjective well-being within social groups.
AB  - Five candidate measures of psychological need-satisfaction were evaluated as
      predictors of high positive and low negative mood within the group, intrinsic
      motivation for group activities, and high commitment to the group. Consistent
      with self-determination theory (Deci & Ryan, 1991), personal autonomy and
      interpersonal relatedness both predicted positive outcomes. Consistent with
      optimal distinctiveness theory (Brewer, 1991), feeling included within the group,
      feeling personally distinctive within the group, and feeling that the group is
      distinctive compared to other groups, also predicted positive outcomes.
      Simultaneous regression analyses indicated that the five needs were
      differentially related to the different well-being indicators, and also suggested
      that group inclusion may be the most important need to satisfy within group
      contexts. Supplementary analyses showed that members of formal groups felt less
      personal autonomy, but more group distinctiveness, compared to informal group
      members.

PMID- 11970773
TI  - The relation between perceived inequity, marital satisfaction and emotions among
      couples facing cancer.
AB  - The central aim of the present study was to examine if equity theory still
      applies to intimate relationships when couples are confronted with a serious
      illness. Equity concerns were examined among 68 cancer patients and their
      partners. Contrary to our expectations, only male patients on average felt
      overbenefited in their relationship, whereas female patients on average felt
      equitably treated. Moreover, it was found that the partners of these patients did
      not, as was expected, feel underbenefited in their relationship. The main focus
      of the present study was on the association between perceived equity on the one
      hand and relationship satisfaction and emotions on the other. It was found that
      in general patients seemed most sensitive to underbenefit (i.e. they felt least
      satisfied), and experienced on average least positive and most negative affect
      when they felt underbenefited. Particularly, patients who were physically
      impaired felt dissatisfied and angry when underbenefited. The partners of these
      patients were in general equally sensitive to inequity in both directions,
      regardless of their ill partner's physical condition.

PMID- 11970774
TI  - Social identity as both cause and effect: the development of group identification
      in response to anticipated and actual changes in the intergroup status hierarchy.
AB  - This study investigates how in-group identification develops during group
      interaction and forms a dynamic input and output that changes over time. Phase 1
      of the study shows how initial level of identification in combination with
      anticipated changes in the intergroup status hierarchy, predicts subsequent
      levels of identification. Whereas low identifiers only express solidarity with
      their group to the extent that the improvement of group status constitutes a
      likely prospect, high identifiers maintain commitment even if their group faces
      an uncertain or bleak future. During Phase 2 of the study, it is shown how low
      and high identifiers respond differently to actual changes in the intergroup
      status structure. Overall, low identifiers seem more instrumental than high
      identifiers, in the sense that the former are only prepared to affirm
      identification with a low status group when status improvement is imminent, or
      has actually been realized. These results are discussed with reference to social
      identity theory.

PMID- 11970775
TI  - The prediction of attitudes from beliefs and evaluations: the logic of the double
      negative.
AB  - One of the most intriguing aspects of Fishbein's (e.g. 1980) theory of reasoned
      action is the logic of the double negative: if a behaviour is thought to be
      unlikely to result in a negatively evaluated consequence, then the product of the
      two negatives (an unlikely consequence that is negatively valued) is thought to
      provide an impetus for the formation of a positive attitude towards the
      behaviour. The present experiment tested two derivations from the logic of the
      double negative. First, according to this logic, whether beliefs and evaluations
      are positively or negatively framed should not affect their ability to predict
      attitudes. Second, the multiplicative assumption of this logic (a negative x
      negative = a positive) suggests that a multiplicative model should be a superior
      predictor of attitudes compared to an additive model that does not allow for the
      logic of the double negative. The obtained findings contradicted both of these
      predictions.

PMID- 11970776
TI  - Are essentialist beliefs associated with prejudice?
AB  - Gordon Allport (1954) proposed that belief in group essences is one aspect of the
      prejudiced personality, alongside a rigid, dichotomous and ambiguity-intolerant
      cognitive style. We examined whether essentialist beliefs-beliefs that a social
      category has a fixed, inherent, identity-defining nature-are indeed associated in
      this fashion with prejudice towards black people, women and gay men. Allport's
      claim, which is mirrored by many contemporary social theorists, received partial
      support but had to be qualified in important respects. Essence-related beliefs
      were associated strongly with anti-gay attitudes but only weakly with sexism and
      racism, and they did not reflect a cognitive style that was consistent across
      stigmatized categories. When associations with prejudice were obtained, only a
      few specific beliefs were involved, and some anti-essentialist beliefs were
      associated with anti-gay attitudes. Nevertheless, the powerful association that
      essence-related beliefs had with anti-gay attitudes was independent of
      established prejudice-related traits, indicating that they have a significant
      role to play in the psychology of prejudice.

PMID- 11970777
TI  - Evidence that perceived behavioural control is a multidimensional construct:
      perceived control and perceived difficulty.
AB  - Four studies were performed to test whether Ajzen's (1988, 1991) concept of
      perceived behavioural control is really an amalgamation of two variables, which
      we term 'perceived control' and 'perceived difficulty'. Perceived control refers
      to the extent to which people consider the performance of a behaviour to be under
      their voluntary control. Perceived difficulty refers to whether people consider a
      behaviour to be easy or difficult to perform, Findings from Studies 1 to 4
      demonstrate that it is possible to perform manipulations that affect perceived
      control more than perceived difficulty, or that affect perceived difficulty more
      than perceived control. Studies 2-4 used a variety of paradigms to show that
      people distinguish between beliefs that are presumed to underlie perceived
      control and perceived difficulty. Finally, we performed a meta-analysis in Study
      5 to determine whether perceived control or perceived difficulty is more
      important for predicting behavioural intentions and behaviours. Taken together,
      the findings support the distinction between perceived control and perceived
      difficulty, and also suggest that perceived difficulty is a better predictor of
      most behavioural intentions and behaviours than is perceived control.

PMID- 11970778
TI  - Category activation effects in judgment and behaviour: the moderating role of
      perceived comparability.
AB  - Previous research on category activation effects demonstrates that extreme
      exemplar priming can lead to contrast effects as well as assimilation effects in
      target judgments. Two experiments extended this line of research by investigating
      the moderating role of perceived comparability, that is, the extent to which the
      exemplar and target are believed to belong to the same category and thus can be
      compared. In both experiments, participants judged the speed of a person
      displayed on a picture following priming with animals exemplifying either extreme
      speed ('cheetah') or extreme slowness ('turtle'). In addition, in the second
      experiment a behavioural measure was included. In the first experiment individual
      differences concerning the perceived comparability between animals and humans
      were assessed. In the second experiment perceived comparability was
      experimentally varied. Results showed that the direction of category activation
      effects (i.e. assimilation versus contrast) depended on the extent to which the
      prime and target categories were seen as comparable. Contrast effects on both
      judgments and behaviour emerged when the prime and the target category were
      perceived as comparable. However, assimilation effects on judgment and behaviour
      ensued when the prime and target category were not perceived as comparable.

PMID- 11970779
TI  - A cross-cultural study of the Need for Cognitive Closure Scale: comparing its
      structure in Croatia, Italy, USA and The Netherlands.
AB  - This study was designed to compare the factor structure of Need for Closure Scale
      (NFCS) as it emerges from three European samples (Croatia, Italy and The
      Netherlands) to the structure emerging from a USA sample, and to test the
      invariance of the structure of the scale both across three European contexts and
      across European and US samples. This comparison was conducted to examine the
      generalizability of results obtained with the NFCS across cultures. The sample
      sizes employed in this study range from 201 (Croatia) to 418 (Italy)
      participants. First- and second-order confirmatory factor analysis and multiple
      group measurement invariance tests were performed using the LISREL-8 program
      (Joreskog and Sorbom, 1993). The analyses revealed that the factor structure of
      the scale was invariant across all samples, and that the best fitting model was
      one with two latent second-order factors, thus confirming results of previous
      studies (Kruglanski et al., 1997; Neuberg, Judice, & West, 1997).

PMID- 11970780
TI  - Effects of stereotypes on attitude inference: outgroups are black and white,
      ingroups are shaded.
AB  - This study examines whether stereotypic expectancies about the attitudes of group
      members (teachers vs. students) affect the attitude inferred from a series of
      statements. Stereotypes can produce either assimilation, contrast or no effects.
      Because ingroups are seen as more variable than outgroups, it is possible that
      assimilation is easily accomplished in ingroup members because of high category
      width, whereas contrast is more likely for outgroups who are seen as homogenous.
      Alternatively, because people are motivated to allocate cognitive resources when
      processing information about ingroup members, it is also possible that contrast
      occurs more frequently for ingroups, or that no stereotype effects emerge because
      the members are not stereotyped. The results indicate that both contrast and
      assimilation effects are stronger for outgroup than for ingroup members. It is
      concluded that outgroup members are categorized as either typical or atypical of
      their group, whereas ingroup members can also occupy intermediate positions.

PMID- 11970781
TI  - Covert reorienting and inhibition of return: an event-related fMRI study.
AB  - Using event-related fMRI, we analyzed the functional neuroanatomy of covert
      reorienting and inhibition of return (IOR). Covert reorienting to a target
      appearing within 250 msec after an invalid contralateral location cue elicited
      increased activation in the left fronto-polar cortex (LFPC), right anterior and
      left posterior middle frontal gyrus, and right cerebellum, areas that have
      previously been associated with attentional processes, specifically attentional
      change. In contrast, IOR, which leads to prolonged response times to targets that
      appear at the cued location at a stimulus-onset-asynchrony (SOA)>250 msec, was
      accompanied by increased activation in brain areas involved in oculomotor
      programming, such as the right medial frontal gyrus (supplementary eye field;
      SEF) and the right inferior precentral sulcus (frontal eye field; FEF),
      supporting the oculomotor bias theory of IOR. Pre-SEF and pre-FEF areas were
      involved both in covert reorienting and IOR. The supramarginal gyri were
      bilaterally involved in IOR, with the right supramarginal gyrus additionally
      involved in covert reorienting.

PMID- 11970782
TI  - Neural specialization for letter recognition.
AB  - Functional magnetic resonance imaging (fMRI) was used to estimate neural activity
      while subjects viewed strings of consonants, digits, and shapes. An area on or
      near the left fusiform gyrus was found that responded significantly more to
      letters than digits. Similar results were obtained when consonants were used
      whose visual features were matched with the digits and when an active matching
      task was used, suggesting that the results cannot be easily attributed to
      artifacts of the stimuli or task. These results demonstrate that neural
      specialization in the human brain can extend to a category of stimuli that is
      culturally defined and that is acquired many years postnatally.

PMID- 11970783
TI  - fMRI study of cognitive interference processing in females with fragile X
      syndrome.
AB  - Females with fragile X syndrome, the most common form of inherited developmental
      and learning problems, are known to be impaired in executive function. The
      current study is the first to investigate the performance of females with fragile
      X on a cognitive interference task utilizing functional magnetic resonance
      imaging (fMRI). Fourteen females with fragile X and 14 age-matched healthy
      controls were imaged while they performed a counting Stroop interference task.
      Compared to controls, females with fragile X appeared to have longer reaction
      times during the interference condition of the task, and adopted a strategy
      trading speed for accuracy. Females with fragile X also had a significantly
      different pattern of activation than controls. Whereas controls showed
      significant activation in the inferior/middle frontal gyrus and inferior/superior
      parietal lobe, females with fragile X showed more extensive activation in the
      anterior region of the prefrontal cortex, and failed to show expected activation
      in the inferior/superior parietal lobe. Further, between-group analyses revealed
      that females with fragile X had reduced activation in the left orbitofrontal
      gyrus, thought to be involved in modulating goal-directed behavior. Females with
      fragile X also demonstrated a markedly different pattern of deactivation from
      controls. These findings suggest that deficits in cognitive interference
      processing during the counting Stroop task observed in females with fragile X may
      arise from inability to appropriately recruit and modulate lateral prefrontal and
      parietal resources.

PMID- 11970784
TI  - Impact of fMRI acoustic noise on the functional anatomy of visual mental imagery.
AB  - One drawback of functional magnetic resonance imaging (fMRI) is that the subject
      must endure intense noise during testing. We examined the possible role of such
      noise on the activation of early visual cortex during visual mental imagery. We
      postulated that noise may require subjects to work harder to pay attention to the
      task, which in turn could alter the activation pattern found in a silent
      environment. To test this hypothesis, we used positron emission tomography (PET)
      to monitor regional Cerebral Blood Flow (rCBF) of six subjects while they
      performed an imagery task either in a silent environment or in an "fMRI-like"
      noisy environment. Both noisy and silent imagery conditions, as compared to their
      respective baselines, resulted in activation of a bilateral fronto-parietal
      network (related to spatial processing), a bilateral inferior temporal area
      (related to shape processing), and deactivation of anterior calcarine cortex.
      Among the visual areas, rCBF increased in the most posterior part of the
      calcarine cortex, but at level just below the statistical threshold. However,
      blood flow values in the calcarine cortex during the silent imagery condition
      (but not the noisy imagery condition) were strongly negatively correlated with
      accuracy; the more challenging subjects found the task, the more strongly the
      calcarine cortex was activated. The subjects made more errors in the noisy
      condition than in the silent condition, and a direct comparison of the two
      conditions revealed that noise resulted in an increase in rCBF in the anterior
      cingulate cortex (involved in performance monitoring) and in the Wernicke's area
      (required to encode the verbal cues used in the task). These results thus
      demonstrate a nonadditive effect of fMRI gradient noise, resulting in a slight
      but significant effect on both performance and the neural activation pattern.

PMID- 11970785
TI  - Visual categorization and object representation in monkeys and humans.
AB  - We investigated the influence of a categorization task on the extraction and
      representation of perceptual features in humans and monkeys. The use of
      parameterized stimuli (schematic faces and fish) with fixed diagnostic features
      in combination with a similarity-rating task allowed us to demonstrate perceptual
      sensitization to the diagnostic dimensions of the categorization task for the
      monkeys. Moreover, our results reveal important similarities between human and
      monkey visual subordinate categorization strategies. Neither the humans nor the
      monkeys compared the new stimuli to class prototypes or based their decisions on
      conditional probabilities along stimulus dimensions. Instead, they classified
      each object according to its similarity to familiar members of the alternative
      categories, or with respect to its position to a linear boundary between the
      learned categories.

PMID- 11970786
TI  - Specialization of neural mechanisms underlying face recognition in human infants.
AB  - Newborn infants respond preferentially to simple face-like patterns, raising the
      possibility that the face-specific regions identified in the adult cortex are
      functioning from birth. We sought to evaluate this hypothesis by characterizing
      the specificity of infants' electrocortical responses to faces in two ways: (1)
      comparing responses to faces of humans with those to faces of nonhuman primates;
      and 2) comparing responses to upright and inverted faces. Adults' face-responsive
      N170 event-related potential (ERP) component showed specificity to upright human
      faces that was not observable at any point in the ERPs of infants. A putative
      "infant N170" did show sensitivity to the species of the face, but the
      orientation of the face did not influence processing until a later stage. These
      findings suggest a process of gradual specialization of cortical face processing
      systems during postnatal development.

PMID- 11970787
TI  - Categorical perception of happiness and fear facial expressions: an ERP study.
AB  - Behavioral studies have shown that two different morphed faces perceived as
      reflecting the same emotional expression are harder to discriminate than two
      faces considered as two different ones. This advantage of between-categorical
      differences compared with within-categorical ones is classically referred as the
      categorical perception effect. The temporal course of this effect on fear and
      happiness facial expressions has been explored through event-related potentials
      (ERPs). Three kinds of pairs were presented in a delayed same-different matching
      task: (1) two different morphed faces perceived as the same emotional expression
      (within-categorical differences), (2) two other ones reflecting two different
      emotions (between-categorical differences), and (3) two identical morphed faces
      (same faces for methodological purpose). Following the second face onset in the
      pair, the amplitude of the bilateral occipito-temporal negativities (N170) and of
      the vertex positive potential (P150 or VPP) was reduced for within and same pairs
      relative to between pairs. This suggests a repetition priming effect. We also
      observed a modulation of the P3b wave, as the amplitude of the responses for the
      between pairs was higher than for the within and same pairs. These results
      indicate that the categorical perception of human facial emotional expressions
      has a perceptual origin in the bilateral occipito-temporal regions, while typical
      prior studies found emotion-modulated ERP components considerably later.

PMID- 11970788
TI  - Discourse representation in the two cerebral hemispheres.
AB  - Readers construct at least two interrelated representations when they comprehend
      a text: (a) a propositional representation containing the individual ideas that
      are derived from each sentence and the relations among them and (b) a discourse
      model, a representation of the context or situation to which the text refers. We
      used a paradigm called "item priming in recognition" to examine how these
      representations are stored in the cerebral hemispheres. In Experiment 1, the
      priming paradigm was used in combination with a lateralized visual field (VF)
      procedure. We found evidence that readers' representations were structured
      according to propositional relations, but only in the left hemisphere. Item
      recognition was facilitated when a concept was preceded by another concept from
      the same proposition when targets were presented to the left, but not to the
      right, hemisphere. We found priming in both hemispheres, however, when targets
      were context-appropriate senses of ambiguous words or topics of passages. In
      Experiment 2, we replicated the priming effects in three callosotomy patients. We
      argue that the distinction between a propositional representation and a discourse
      model is important with respect to how discourse is represented in the brain. The
      propositional representation appears to reside in the left hemisphere, whereas
      aspects of the discourse model appear to be represented in both hemispheres.

PMID- 11970789
TI  - Blindsight after optic nerve injury indicates functionality of spared fibers.
AB  - Some patients with lesions in the geniculostriate pathway (GSP) can respond to
      visual stimuli in the blind field without conscious acknowledgement. The
      substrate for this "blindsight" is controversial: whether it is the uninjured
      extrastriate pathway (EXP), which bypasses the lesion site, or residual fibers
      within damaged visual cortex ("islands of vision"). Using stimulus detection,
      localization, and spatial summation tasks, we have found blindsight in patients
      with damage both in the optic nerve (ON) and EXP. The prevalence and functional
      characteristics of their blindsight are indistinguishable from that in patients
      with GSP lesions, so blindsight does not require a completely intact EXP. The
      present findings support the view that a few surviving ON axons within an area of
      primary damage are sufficient to mediate blindsight: Several combinations of
      partially intact pathways can transmit information to the extrastriate cortex and
      the sum of activation of all visual fibers surviving the injury determines if and
      to what extent blindsight occurs.

PMID- 11970790
TI  - Cross-modal interactions between audition, touch, and vision in endogenous
      spatial attention: ERP evidence on preparatory states and sensory modulations.
AB  - Recent behavioral and event-related brain potential (ERP) studies have revealed
      cross-modal interactions in endogenous spatial attention between vision and
      audition, plus vision and touch. The present ERP study investigated whether these
      interactions reflect supramodal attentional control mechanisms, and whether
      similar cross-modal interactions also exist between audition and touch.
      Participants directed attention to the side indicated by a cue to detect
      infrequent auditory or tactile targets at the cued side. The relevant modality
      (audition or touch) was blocked. Attentional control processes were reflected in
      systematic ERP modulations elicited during cued shifts of attention. An anterior
      negativity contralateral to the cued side was followed by a contralateral
      positivity at posterior sites. These effects were similar whether the cue
      signaled which side was relevant for audition or for touch. They also resembled
      previously observed ERP modulations for shifts of visual attention, thus
      implicating supramodal mechanisms in the control of spatial attention. Following
      each cue, single auditory, tactile, or visual stimuli were presented at the cued
      or uncued side. Although stimuli in task-irrelevant modalities could be
      completely ignored, visual and auditory ERPs were nevertheless affected by
      spatial attention when touch was relevant, revealing cross-modal interactions.
      When audition was relevant, visual ERPs, but not tactile ERPs, were affected by
      spatial attention, indicating that touch can be decoupled from cross-modal
      attention when task-irrelevant.

PMID- 11970791
TI  - Mechanisms underlying spatial representation revealed through studies of
      hemispatial neglect.
AB  - The representations that mediate the coding of spatial position were examined by
      comparing the behavior of patients with left hemispatial neglect with that of
      nonneurological control subjects. To determine the spatial coordinate system(s)
      used to define "left" and "right," eye movements were measured for targets that
      appeared at 5 degrees, 10 degrees, and 15 degrees to the relative left or right
      defined with respect to the midline of the eyes, head, or midsaggital plane of
      the trunk. In the baseline condition, in which the various egocentric midlines
      were all aligned with the environmental midline, patients were disproportionately
      slower at initiating saccades to left than right targets, relative to the
      controls. When either the trunk or the head was rotated and the midline aligned
      with the most peripheral position while the eyes remained aligned with the
      midline of the environment, the results did not differ from the baseline
      condition. However, when the eyes were rotated and the midline aligned with the
      peripheral position, saccadic reaction time (SRT) differed significantly from the
      baseline, especially when the eyes were rotated to the right. These findings
      suggest that target position is coded relative to the current position of gaze
      (oculocentrically) and that this eye-centered coding is modulated by orbital
      position (eye-in-head signal). The findings dovetail well with results from
      existing neurophysiological studies and shed further light on the spatial
      representations mediated by the human parietal cortex.

PMID- 11970792
TI  - Hemispheric processing of categorical and coordinate spatial relations in the
      absence of low spatial frequencies.
AB  - Right-handed participants performed the categorical and coordinate spatial
      relation judgments on stimuli presented to either the left visual field - right
      hemisphere (LVF-RH) or the right visual field - left hemisphere (RVF-LH). The
      stimulus patterns were formulated either by bright dots or contrast-balanced
      dots. When the stimuli were bright, an RVF-LH advantage was observed for the
      categorical task, whereas an LVF-RH advantage was observed for the coordinate
      task. When the stimuli were contrast balanced, the RVF-LH advantage was observed
      for the categorical task, but the LVF-RH advantage was eliminated for the
      coordinate task. Because the contrast-balanced dots are largely devoid by of low
      spatial frequency content, these results suggest that processing of low spatial
      frequency is responsible for the right hemisphere advantage for the coordinate
      spatial processing.

PMID- 11970793
TI  - Striatal contribution to cognition: working memory and executive function in
      Parkinson's disease before and after unilateral posteroventral pallidotomy.
AB  - The basal ganglia are intimately connected to the frontal cortex via five fronto
      striatal circuits. While the role of the frontal cortex in cognition has been
      extensively studied, the contribution of the basal ganglia to cognition has
      remained less clear. In Parkinson's disease, posteroventral pallidotomy (PVP)
      involves surgical lesioning of the internal section of the globus pallidus (GPi,
      the final output pathway from the basal ganglia) to relieve the motor symptoms of
      the disorder. PVP in Parkinson's disease provides a unique opportunity to
      investigate the impact of disruption of striatal outflow to the frontal cortex on
      cognition. We assessed executive function and working memory after withdrawal of
      medication in 13 patients with Parkinson's disease before and 3 months after
      unilateral PVP compared to 12 age- and IQ-matched normals assessed twice with an
      interval of 3 months. The tests used were: Wisconsin Card Sorting (WCST), Self
      Ordered Random Number Sequences, Missing Digit Test, Paced Visual Serial Addition
      Test (PVSAT), and Visual Conditional Associative Learning Test (VCALT). After
      PVP, the patients performed significantly better on the Self-Ordered Random
      Number Sequences and the WCST, an improvement that was also observed in the
      normals across the two assessment and is therefore likely to reflect practice
      effects. Relative to the normals, the patients showed significant differential
      change following PVP on the Missing Digit Test and PVSAT, on which they performed
      worse after compared to before surgery, while the controls performed better on
      the second assessment. For the patients, performance on the VCALT also indicated
      deterioration after PVP, but the changes approached significance. The side of PVP
      had no effect on the results. The pattern of change observed 3 months after PVP
      was maintained at 15-month follow-up. The results suggest that striatal outflow
      to the frontal cortex may be essential for those aspects of executive function
      that showed deterioration after PVP.

PMID- 11970794
TI  - Separating storage from retrieval dysfunction of temporal memory in Parkinson's
      disease.
AB  - Dysfunction of the basal ganglia and the brain nuclei interconnected with them
      leads to disturbances of movement and cognition exemplified in Parkinson's
      disease (PD) and Huntington's disease, including disordered timing of movements
      and impaired time estimation. Previous research has shown that whereas striatal
      damage in animals can result in the loss of temporal control over behavior,
      dopaminergic deregulation in the human striatum associated with PD distorts the
      memory for time. Here we show a dissociation between deficits in storage (writing
      to) and retrieval (reading from) temporal memory processes. Both are
      dysfunctional in PD and sensitive to treatment with dopaminergic agents, but
      produce dissimilar distortions. When time intervals are stored in memory while
      the subjects are dopamine depleted, the process is slowed, leading to
      overestimation of two different time intervals. Conversely, when retrieval occurs
      in a dopamine-depleted state, interference or coupling occurs between two
      remembered time intervals, producing overestimation of the shorter and
      underestimation of the longer one. Whether those two separable patterns of
      dysfunction in storing and retrieving temporal memories rely on distinct neural
      networks within the basal ganglia and/or their cortical targets remains to be
      answered by future research.

PMID- 11970795
TI  - The psychophysiology of real-time financial risk processing.
AB  - A longstanding controversy in economics and finance is whether financial markets
      are governed by rational forces or by emotional responses. We study the
      importance of emotion in the decision-making process of professional securities
      traders by measuring their physiological characteristics (e.g., skin conductance,
      blood volume pulse, etc.) during live trading sessions while simultaneously
      capturing real-time prices from which market events can be detected. In a sample
      of 10 traders, we find statistically significant differences in mean
      electrodermal responses during transient market events relative to no-event
      control periods, and statistically significant mean changes in cardiovascular
      variables during periods of heightened market volatility relative to normal
      volatility control periods. We also observe significant differences in these
      physiological responses across the 10 traders that may be systematically related
      to the traders' levels of experience.

PMID- 11970796
TI  - Testing the efficiency and independence of attentional networks.
AB  - In recent years, three attentional networks have been defined in anatomical and
      functional terms. These functions involve alerting, orienting, and executive
      attention. Reaction time measures can be used to quantify the processing
      efficiency within each of these three networks. The Attention Network Test (ANT)
      is designed to evaluate alerting, orienting, and executive attention within a
      single 30-min testing session that can be easily performed by children, patients,
      and monkeys. A study with 40 normal adult subjects indicates that the ANT
      produces reliable single subject estimates of alerting, orienting, and executive
      function, and further suggests that the efficiencies of these three networks are
      uncorrelated. There are, however, some interactions in which alerting and
      orienting can modulate the degree of interference from flankers. This procedure
      may prove to be convenient and useful in evaluating attentional abnormalities
      associated with cases of brain injury, stroke, schizophrenia, and attention
      deficit disorder. The ANT may also serve as an activation task for neuroimaging
      studies and as a phenotype for the study of the influence of genes on attentional
      networks.

PMID- 11970798
TI  - Saccadic inhibition in voluntary and reflexive saccades.
AB  - The present study investigated saccadic inhibition in both voluntary and stimulus
      elicited saccades. Two experiments examined saccadic inhibition caused by an
      irrelevant flash occurring subsequent to target onset. In each trial,
      participants were required to perform a single saccade following the presentation
      of a black target on a gray background, 4 degrees to the left or to the right of
      screen center. In some trials (flash trials), after a variable delay, a 33-msec
      flash was displayed at the top and bottom third of the monitor (these regions
      turned white). In all experimental conditions, histograms of flash-to-saccade
      latencies documented a decrease in saccadic frequency, forming a dip, time-locked
      to the flash and occurring as early as 60-70 msec following its onset. The fast
      latency of this effect strongly suggests a low-level, reflex-like, oculomotor
      effect, which was referred to as saccadic inhibition. A novel procedure was
      developed to allow comparisons of saccadic inhibition even across conditions,
      which in the absence of a flash (no-flash trials) produce dissimilar saccadic
      reaction times (SRTs) distributions. Experiment 1 examined the effects of the
      fixation stimulus on saccadic inhibition by contrasting three conditions: a gap
      condition (fixation stimulus disappeared 200 msec prior to target onset), a step
      condition (offset of the fixation stimulus was simultaneous with target onset),
      and an overlap condition (the fixation stimulus remained on for the duration of
      the trial). The overlap condition produced substantially stronger saccadic
      inhibition, relative to the gap and the step conditions. Experiment 2 contrasted
      the saccadic inhibition effect obtained for prosaccades (saccades aimed at the
      target) with the effect obtained for antisaccades (i.e., saccades aimed away from
      the same target). The onset of saccadic inhibition was earlier, and its magnitude
      was stronger, for antisaccades, relative to prosaccades. The plausibility that
      the superior colliculus is the neurophysiological locus of the saccadic
      inhibition effect was explored.

PMID- 11970797
TI  - GABA-ergic modulation of prefrontal spatio-temporal activation pattern during
      emotional processing: a combined fMRI/MEG study with placebo and lorazepam.
AB  - Various prefrontal cortical regions have been shown to be activated during
      emotional stimulation, whereas neurochemical mechanisms underlying emotional
      processing in the prefrontal cortex remain unclear. We therefore investigated the
      influence of the GABA-A potentiator lorazepam on prefrontal cortical emotional
      motor spatio-temporal activation pattern in a combined functional magnetic
      resonance imaging/magnetoencephalography study. Lorazepam led to the reversal in
      orbito-frontal activation pattern, a shift of the early magnetic field dipole
      from the orbito-frontal to medial prefrontal cortex, and alterations in
      premotor/motor cortical function during negative and positive emotional
      stimulation. It is concluded that negative emotional processing in the orbito
      frontal cortex may be modulated either directly or indirectly by GABA-A
      receptors. Such a modulation of orbito-frontal cortical emotional function by
      lorazepam has to be distinguished from its effects on cortical motor function as
      being independent from the kind of processing either emotional or nonemotional.

PMID- 11970799
TI  - Supramodal effects of covert spatial orienting triggered by visual or tactile
      events.
AB  - Event-related functional magnetic resonance imaging was used to identify brain
      areas involved in spatial attention and determine whether these operate
      unimodally or supramodally for vision and touch. On a trial-by-trial basis, a
      symbolic auditory cue indicated the most likely side for the subsequent target,
      thus directing covert attention to one side. A subsequent target appeared in
      vision or touch on the cued or uncued side. Invalidly cued trials (as compared
      with valid trials) activated the temporo-parietal junction and regions of
      inferior frontal cortex, regardless of target modality. These brain areas have
      been associated with multimodal spatial coding in physiological studies of the
      monkey brain and were linked to a change in the location that must be attended to
      in the present study. The intraparietal sulcus and superior frontal cortex were
      also activated in our task, again, regardless of target modality, but did not
      show any specificity for invalidly cued trials. These results identify a
      supramodal network for spatial attention and reveal differential activity for
      inferior circuits involving the temporo-parietal junction and inferior frontal
      cortex (specific to invalid trials) versus more superior intraparietal-frontal
      circuits (common to valid and invalid trials).

PMID- 11970801
TI  - Deactivation of sensory-specific cortex by cross-modal stimuli.
AB  - Visual and auditory cortices traditionally have been considered to be "modality
      specific." Thus, their activity has been thought to be unchanged by information
      in other sensory modalities. However, using functional magnetic resonance imaging
      (fMRI), the present experiments revealed that ongoing activity in the visual
      cortex could be modulated by auditory information and ongoing activity in the
      auditory cortex could be modulated by visual information. In both cases, this
      cross-modal modulation of activity took the form of deactivation. Yet, the
      deactivation response was not evident in either cortical area during the paired
      presentation of visual and auditory stimuli. These data suggest that cross-modal
      inhibitory processes operate within traditional modality-specific cortices and
      that these processes can be switched on or off in different circumstances.

PMID- 11970800
TI  - Episodic action memory for real objects: an ERP investigation with perform,
      watch, and imagine action encoding tasks versus a non-action encoding task.
AB  - Cognitive research shows that people typically remember actions they perform
      better than those that they only watch or imagine doing, but also at times
      misremember doing actions they merely imagined or planned to do (source memory
      errors). Neural research suggests some overlap between brain regions engaged
      during action production, motor imagery, and action observation. The present
      study evaluates the similarities/differences in brain activity during the
      retrieval of various types of action and nonaction memories. Participants study
      real objects in one of four encoding conditions: performing an action, watching
      the experimenter perform an action, or imagining an action with an object, or a
      nonmotoric task of estimating an object's cost. At test, participants view color
      photos of the objects, and make source memory judgments about the initial
      encoding episodes. Event-related potentials (ERPs) during test reveal (1) content
      specific brain activity depending on the nature of the encoding task, and (2) a
      hand tag, i.e., sensitivity to the hand with which an object had been manipulated
      at study. At fronto-central sites, ERPs are similar for the three action
      retrieval conditions, which are distinct from those to the cost-encoded objects.
      At occipital sites ERPs distinguished objects from encoding conditions with
      visual motion (Perform and Watch) from those without visual motion (Imagine and
      Cost). Results thus suggest some degree of recapitulation of encoding brain
      activity during retrieval of memories with qualitatively distinct attributes.

PMID- 11970802
TI  - Automatic and controlled processing of melodic contour and interval information
      measured by electrical brain activity.
AB  - Most work on how pitch is encoded in the auditory cortex has focused on tonotopic
      (absolute) pitch maps. However, melodic information is thought to be encoded in
      the brain in two different "relative pitch" forms, a domain-general contour code
      (up/down pattern of pitch changes) and a music-specific interval code (exact
      pitch distances between notes). Event-related potentials were analyzed in
      nonmusicians from both passive and active oddball tasks where either the contour
      or the interval of melody-final notes was occasionally altered. The occasional
      deviant notes generated a right frontal positivity peaking around 350 msec and a
      central parietal P3b peaking around 580 msec that were present only when
      participants focused their attention on the auditory stimuli. Both types of
      melodic information were encoded automatically in the absence of absolute pitch
      cues, as indexed by a mismatch negativity wave recorded during the passive
      conditions. The results indicate that even in the absence of musical training,
      the brain is set up to automatically encode music-specific melodic information,
      even when absolute pitch information is not available.

PMID- 11970803
TI  - Morphological priming in Spanish verb forms: an ERP repetition priming study.
AB  - The ERP repetition priming paradigm has been shown to be sensitive to the
      processing differences between regular and irregular verb forms in English and
      German. The purpose of the present study is to extend this research to a language
      with a different inflectional system, Spanish. The design (delayed visual
      repetition priming) was adopted from our previous study on English, and the
      specific linguistic phenomena we examined are priming relations between different
      kinds of stem (or root) forms. There were two experimental conditions: In the
      first condition, the prime and the target shared the same stem form, e.g., "ando
      andar" [I walk-to walk], whereas in the second condition, the prime contained a
      marked (alternated) stem, e.g., "duermo-dormir" [I sleep-to sleep]. A reduced
      N400 was found for unmarked (nonalternated) stems in the primed condition,
      whereas marked stems showed no such effect. Moreover, control conditions
      demonstrated that the surface form properties (i.e., the different degree of
      phonetic and orthographic overlap between primes and targets) do not explain the
      observed priming difference. The ERP priming effect for verb forms with unmarked
      stems in Spanish is parallel to that found for regularly inflected verb forms in
      English and German. We argue that effective priming is possible because prime
      target pairs such as "ando-andar" access the same lexical entry for their stems.
      By contrast, verb forms with alternated stems (e.g., "duermo") constitute
      separate lexical entries, and are therefore less powerful primes for their
      corresponding base forms.

PMID- 11970804
TI  - Semantic category interference in overt picture naming: sharpening current
      density localization by PCA.
AB  - The study investigated the neuronal basis of the retrieval of words from the
      mental lexicon. The semantic category interference effect was used to locate
      lexical retrieval processes in time and space. This effect reflects the finding
      that, for overt naming, volunteers are slower when naming pictures out of a
      sequence of items from the same semantic category than from different categories.
      Participants named pictures blockwise either in the context of same- or mixed
      category items while the brain response was registered using
      magnetoencephalography (MEG). Fifteen out of 20 participants showed longer
      response latencies in the same-category compared to the mixed-category condition.
      Event-related MEG signals for the participants demonstrating the interference
      effect were submitted to a current source density (CSD) analysis. As a new
      approach, a principal component analysis was applied to decompose the grand
      average CSD distribution into spatial subcomponents (factors). The spatial factor
      indicating left temporal activity revealed significantly different activation for
      the same-category compared to the mixed-category condition in the time window
      between 150 and 225 msec post picture onset. These findings indicate a major
      involvement of the left temporal cortex in the semantic interference effect. As
      this effect has been shown to take place at the level of lexical selection, the
      data suggest that the left temporal cortex supports processes of lexical
      retrieval during production.

PMID- 11970805
TI  - Patterns of bimanual interference reveal movement encoding within a radial
      egocentric reference frame.
AB  - Constraints on interlimb coordination have been studied intensively in past years
      with a primary focus on temporal features. The present study addressed spatial
      constraints or the degree of directional interference as a function of different
      line combinations between the upper limbs as well as the modulation of this
      interference as a result of different board orientations within the performer's
      workspace. This paradigm was used to address a prominent theme in motor
      neuroscience, namely whether (bimanual) movements are encoded within an
      allocentric reference frame (pattern of interference invariant with respect to
      extrinsic space) or within an egocentric reference frame (pattern of interference
      invariant relative to the center of the performer's action space, i.e.,
      intrinsic). The observed patterns of interference revealed that movements are
      primarily encoded within a radial egocentric reference frame in which the
      performer is the center of action space. The present psychophysical findings
      converge with primate single-cell recording studies in which the direction has
      been identified as a primary movement parameter that is encoded in various brain
      regions, thereby constituting a principal determinant of bilateral interference.

PMID- 11970806
TI  - Contributions of the prefrontal cortex and basal ganglia to set shifting.
AB  - Impairments of set shifting have been associated with damage to both the
      prefrontal cortex (PFC) and to the basal ganglia. The purpose of these
      experiments was to determine whether damage to the PFC was associated with
      shifting impairments per se or whether any switching deficits could be attributed
      to a reduction of working memory capacity. In contrast, shifting impairments were
      expected for Parkinson patients regardless of memory load, given that these
      patients seem to have no cognitive deficits other than when having to shift set.
      To vary working memory demands, a cue to the relevant dimension (letter or shape)
      in an odd-man-out task was presented or withheld. Pathology to prefrontal areas
      associated with normal aging was not linked to shifting deficits when working
      memory load was reduced in a comparison of older and younger adults (Experiment
      1). In contrast, set-shifting abilities were still impaired for stroke patients
      with prefrontal damage regardless of working memory demands (Experiment 2).
      Parkinson patients were relatively unimpaired on this task (Experiment 2), but
      began to display shifting deficits when response competition was present in the
      display (Experiment 3).

PMID- 11970807
TI  - Selectively impaired associative learning in older people with cognitive decline.
AB  - Older people with declining cognitive function typically display deficits in
      declarative memory processes, often most evident on tests of associative learning
      (AL). The hippocampal formation (HF) is thought to be critically involved in the
      encoding and retrieval of such associations, consistent with neuroimaging
      findings that the HF is damaged in early stages of neurodegenerative disease and
      in older people with AL impairments. In the clinic, older people with cognitive
      decline commonly report difficulties associating names with faces. However, we
      have observed that such people are particularly impaired on tests requiring the
      association of novel stimuli. In Experiment 1, a series of AL tasks were
      administered to older people with cognitive decline to determine whether they
      were impaired at simply making associations, or at making associations between
      novel stimuli. In Experiment 2, we measured HF function in these subjects by
      administering an AL task designed to differentiate between HF-damaged and HF
      intact individuals. Our experimental protocols were guided by a computational
      model of HF function in AL described by Gluck and Myers (1997). Older people with
      cognitive decline displayed impaired performance on tasks designed to be highly
      dependent upon intact HF function, including a task in which novel patterns and
      spatial locations were to be associated. These results suggest that the AL
      impairments observed in older people with cognitive decline may be due to HF
      dysfunction.

PMID- 11970808
TI  - Dissociation of habit-learning in Parkinson's and cerebellar disease.
AB  - Damage to the medial-temporal region is known to result in declarative (explicit)
      memory deficits but nondeclarative (implicit) memory is largely unaffected by
      such lesions. Earlier studies have shown that some forms of implicit learning
      depend on cerebellar circuits but remain preserved following affections of the
      basal ganglia circuits. It is unknown which forms of implicit learning persist in
      patients with cerebellar pathology but are affected after basal ganglia lesions.
      Therefore, we determined if a test sensitive for habit-learning (probabilistic
      classification task) resulted in normal values for patients with cerebellar
      disease but resulted in affected results in patients with Parkinson's disease
      (PD). To this end, 23 patients with PD, 16 patients with familial or idiopathic
      cerebellar degeneration (CD), and 20 controls were tested for habit-learning.
      There was no impairment of patients with CD for the early learning period but
      there was abnormal learning in the PD group. For a later learning period, the
      patients with the PD showed improved performance. We conclude that the
      probabilistic learning task is an implicit, nonmotor learning task which is
      sensitive for basal ganglia pathology but remains unaffected in the case of
      cerebellar pathology. Such a test may be of special interest for the detection
      and possible neurobehavioral treatment of cognitive and motor deficits.

PMID- 11970809
TI  - An fMRI study on the time-limited role of the medial temporal lobe in long-term
      topographical autobiographic memory.
AB  - The time-limited role of the medial temporal lobe (MTL) in human long-term memory
      is well known. However, there is still no direct neuroimaging evidence to confirm
      it. In this fMRI study, nine subjects were scanned while asked to recall the
      places they visited more than seven years ago (remote memories); and the places
      they visited recently (recent memories). We observed robust and dominant MTL
      activity peaking in the left parahippocampal gyrus when recent memories were
      contrasted with remote memories. This result provided direct evidence for the
      time-limited role of the MTL in long-term topographical autobiographic memory.
      Further analysis revealed that this MTL activity was not due to the fact that the
      retrieval of recent memories was accompanied by more details. When detailed
      recent memories were contrasted with detailed remote memories, there was still
      MTL activity peaking in the left parahippocampal gyrus. The effects of details in
      remote memories are also discussed.

PMID- 11970810
TI  - Neural systems for visual orienting and their relationships to spatial working
      memory.
AB  - We investigated neural correlates of human visual orienting using event-related
      functional magnetic resonance imaging (fMRI). When subjects voluntarily directed
      attention to a peripheral location, we recorded robust and sustained signals
      uniquely from the intraparietal sulcus (IPs) and superior frontal cortex (near
      the frontal eye field, FEF). In the ventral IPs and FEF only, the blood oxygen
      level dependent signal was modulated by the direction of attention. The IPs and
      FEF also maintained the most sustained level of activation during a 7-sec delay,
      when subjects maintained attention at the peripheral cued location (working
      memory). Therefore, the IPs and FEF form a dorsal network that controls the
      endogenous allocation and maintenance of visuospatial attention. A separate right
      hemisphere network was activated by the detection of targets at unattended
      locations. Activation was largely independent of the target's location (visual
      field). This network included among other regions the right temporo-parietal
      junction and the inferior frontal gyrus. We propose that this cortical network is
      important for reorienting to sensory events.

PMID- 11970811
TI  - Possible information bias in a waterborne outbreak investigation.
AB  - Although an investigation of a cryptosporidiosis outbreak in 1994 in Clark
      County, Nevada, concluded that illness was associated with consumption of
      municipal water, no water treatment deficiencies or breakdowns and no water
      quality changes were discovered during the investigation. We evaluated the
      strength of the evidence for waterborne transmission and conducted a sensitivity
      analysis to define the limitations of the epidemiological data. Our analyses
      suggest a spurious inference of waterborne transmission might be due to
      differential misclassification bias. If exposure and disease status were
      incorrectly classified for a relatively small number of study participants,
      findings of the investigation would be interpreted differently. We offer this
      example to illustrate the importance of assessing the stability of a relative
      risk estimate and effect of possible biases during an outbreak investigation.

PMID- 11970812
TI  - Health effect of human wastes use in agriculture in El Azzouzia (the wastewater
      spreading area of Marrakesh city, Morocco).
AB  - The use of wastewater and excreta in agriculture constitutes an important source
      of spread Salmonella strains and protozoan infections into the environment. This
      practice has been used in El Azzouzia (the wastewater-spreading area of Marrakesh
      city, Morocco) for several years. The available circumstantial evidence gained
      from epidemiological and microbiological investigations suggests that the use of
      untreated wastewater causes an excess of protozoan infections among children
      living in El Azzouzia (72%) compared with those from a control area (45%). The
      pathogenic protozoan infections observed were giardiasis (39%) and amoebiasis
      (28%). For Salmonella infection, 21.34% of the exposed children were infected,
      while this rate did not exceed 1.14% in the control group. The serogroups B and C
      were the most commonly isolated. The sewage farming children are therefore more
      exposed to detectable risk from pathogenic micro-organisms than the control
      children.

PMID- 11970813
TI  - Food handlers' beliefs and self-reported practices.
AB  - Despite an increase in the number of food handlers receiving food hygiene
      training, a high proportion of food poisoning outbreaks still occur as a result
      of poor food handling practices. This paper uses elements of social cognitive
      theory to examine the beliefs of food handlers towards food safety and to
      determine food handlers' self-reported practices. Questionnaires were completed
      by 137 food handlers from 52 small to medium-sized food businesses in Wales.
      Generally, food handlers were aware of the food safety actions they should be
      carrying out but identified a number of barriers which would prevent them from
      implementing these practices. These barriers included lack of time, lack of staff
      and a lack of resources. Despite 95% of respondents receiving food hygiene
      training, 63% admitted to sometimes not carrying out food safety behaviours. All
      the food handlers also perceived their business to be of relatively low risk and
      yet all businesses prepared high risk foods. This research highlights the need
      for training to be based around a risk-based approach and demonstrates that
      behavioural change will not occur merely as a result of training. Food safety
      practices will only be implemented given adequate resources and an appropriate
      management culture.

PMID- 11970814
TI  - Bacterial contamination of Japanese households and related concern about
      sanitation.
AB  - The bacterial contamination of Japanese homes and the attitudes of Japanese
      people toward sanitation were studied. By taking bacterial counts of
      approximately 90 places each in five homes, this study found kitchens to have the
      greatest degree of bacterial contamination, followed by bathing rooms. Toilets
      had less bacterial contamination than was expected. While concern about bacteria
      on highly contaminated items such as sponges, towels for wiping counters, and
      other reservoirs/disseminators was common, there was a relative lack of concern
      regarding contact surfaces such as dining tables. It is believed that an in-depth
      study of bacterial contamination in the home and concern about it would lead to
      the promotion of greater public understanding of home sanitation and help to
      facilitate the provision of useful information and products to the public.

PMID- 11970815
TI  - The risk of enteric diseases in young children and environmental indicators in
      sentinel areas of Mexico City.
AB  - The overall objective of this study is to promote the development of
      environmental health indicators in Mexico City. Specific examples focused on
      water quality, household characteristics e.g., sanitation and risk of enteric
      diseases. A geographic information system (GIS) was used in order to identify
      eligible wells and their surrounding homesteads (0.5 km around each well). A
      pilot study was conducted during the rainy season (1999), and a total of 1, 250
      eligible households were visited on a random sample basis; only those having
      children under 5 years of age were interviewed. Data on diarrheal disease (i.e.
      occurrence in the previous two weeks) were obtained from 950 children, and their
      guardians provided information on their water supply, sanitation and
      socioeconomic variables. A total of 320 water samples were obtained from 40
      wells, and tested for Total coliforms (TC/100 ml), Fecal coliforms (FC/100 ml).
      Escherichia coli (EC) and Fecal streptococci (FS). Bacterial indicators were
      detected in 40% of the wells in the western zone and in 32% of the southern zone
      (p = 0.01). The rate of diarrheal diseases was higher for children from the
      southern areas than in the west (OR = 1.7 and 95% CI: 0.99, 2.86). The final
      analysis showed a higher risk of diarrhea in children from rented homes than
      those living in owned dwellings (OR = 1.7 and 95% Cl: 1.04, 2.77): the risk was
      also highest for children living in houses with poor sanitation facilities (e.g.,
      latrine) than those connected to a sewerage (OR = 1.7 and 95% Cl: 1.00, 2.93).
      Children from households perceiving unpleasant taste of water showed a higher
      risk than those without complaints (OR = 2.2 and 95% Cl: 1.28, 3.75). Linkages
      between environmental factors and health risk were created from spatially
      distributed information, and the proposed environmental health indicator (EHI)
      summarized the most significant predictors of diarrheal diseases. This baseline
      information may contribute to further environmental health investigation and
      policy making analysis.

PMID- 11970816
TI  - Water usage patterns in low-income urban communities in Uganda: implications for
      water supply surveillance.
AB  - The selection of water sources by poor households in three urban areas in Uganda
      is shown to be complex, with a range of communal water sources used. In all
      towns, significant numbers of households used multiple sources. An aggregated
      estimate of the level of use in the largest town, Kampala, showed little
      difference in the number of households collecting water from piped and non-piped
      sources. In the other towns, households in Soroti were more likely to use point
      sources than piped water and in Masaka most households used piped water, with
      unprotected sources the most common subsidiary source. Differentiation in use by
      source type was evaluated. In two of the towns no differentiation in use is seen.
      In Soroti, some differentiation in use is seen as the water from boreholes is
      widely used for drinking and that from other sources less frequently consumed.
      Supplemental water purchased from vendors was relatively uncommon in the towns,
      but two towns showed that many households collect rainwater for domestic use. The
      implications of these findings for the drinking water surveillance programme are
      discussed.

PMID- 11970817
TI  - Spectral ultraviolet albedo of roofing surfaces and human facial exposure.
AB  - Spectral field measurements were used to quantify the ultraviolet (UV) spectral
      albedos of four different metallic roofing surfaces. The effect of the albedos of
      two of these surfaces on erythemal exposure to human facial anatomical sites was
      quantified by UV dosimetry. The albedos of all roofing surfaces were greater than
      the albedo of grass. Little SZA dependence was observed for any of the surfaces.
      The albedos of the coloured metallic corrugated surfaces were strongly dependent
      on wavelength in the UVA, increasing from 3 to 12%. Facial erythemal measurements
      showed significant exposure enhancements over the galvanised corrugated surface
      compared to grass. The undersides of the chin and nose received exposure
      enhancements over the galvanised corrugated surface of about 1290 and 190%,
      respectively, of the exposure of these sites over grass. It is concluded that the
      albedo of the galvanised surfaces are higher than those of the coloured surfaces
      by at least 20%, and higher than grass by at least 27%. Consequently, normally
      shaded facial anatomical sites receive substantially higher UV exposures over
      these galvanised surfaces compared to grass.

PMID- 11970818
TI  - Monitoring of polycyclic aromatic hydrocarbons in seafoods from Lake Timsah.
AB  - Concentrations of polycyclic aromatic hydrpcarvons (PAHs) in some seafoods caught
      from Lake Timsah were determined. The tested samples were tilapia fish
      (Oreochromis aureus), crabs (Portuns pelagicus), bivalves (Venerupis decussata),
      clams (Strombus tricornis) and gastropods (Munes Sp.). Where these seafoods are
      locally and favorite consumed foods in the area around the lake (Ismailia
      governorate). Results showed that crabs contained significantly higher
      concentrations of both total and carcinogenic PAHs ranging from 1318.6 to 3767.4
      and 1230.3 to 3442.2 microg kg(-1), respectively. Meanwhile, clams contained
      significantly lower levels with mean value of 28.4 microg kg(-1) for total and
      24.4 microg kg(-1) for carcinogenic PAHs. The most frequently detected PAHs in
      the tested samples were indeno(1,2,3-cd)pyrene followed by benzo(a)pyrene,
      dibenzo(a,h)anthracene, and benzo(b)fluoranthene which are characterized as
      carcinogenic compounds.

PMID- 11970819
TI  - Indoor biological contaminants and symptoms of sick building syndrome in office
      buildings in Mauritius.
AB  - This study was carried out to investigate possible relationship between bio
      contaminants and symptoms of sick building syndrome among office workers in
      Mauritius. Viable microbial colonies were collected using a Casella slit sampler
      in 23 selected indoor office buildings. A questionnaire survey as well as a walk
      through investigation was undertaken. Physico-chemical measurements were also
      monitored in the selected offices. Results of this study showed that number of
      indoor bacterial bioaerosol concentrations ranged between 3 and 1110 CFU/m(3)
      while fungal counts were 0-196 CFU/m(3). However, most of the buildings showed
      absence of dust mites. In conclusions fungal contamination was found to be
      associated with the onset of sick building syndrome symptoms among workers in
      office buildings in Mauritius.

PMID- 11970820
TI  - Risk of adverse reactions from contaminants in Chinese herbal medicines can be
      minimized by using quality products and qualified practitioners.

PMID- 11970837
TI  - Redox regulation of neutrophil function.

PMID- 11970838
TI  - The effect of hypochlorous acid on the expression of adhesion molecules and
      activation of NF-kappaB in cultured human endothelial cells.
AB  - Exposure to oxidants can up-regulate the expression of adhesion molecules in
      endothelial cells with a consequent increase in neutrophil attachment. Similarly,
      the transcription factor nuclear factor-kappaB (NF-kappaB), which controls the
      expression of the intercellular adhesion molecules (ICAMs), can also be activated
      by oxidants in some cells. We have investigated whether hypochlorous acid (HOCl),
      the major strong oxidant produced by neutrophils, can affect the expression of
      adhesion molecules on human umbilical vein endothelial cells (HUVEC) and promote
      neutrophil adhesion. We found that HOCl could induce an increase in neutrophil
      adhesion to the endothelial cells after 60 min of treatment. Activation of NF
      kappaB could be detected under similar conditions. However, the dose of HOCl
      required for this effect resulted in considerable longer-term toxicity to the
      cells. Treatment of HUVEC with sublethal doses of HOCl had no effect on NF-kappaB
      activation, neutrophil adhesion, or the surface expression of E-selectin, ICAM-1,
      or P-selectin. However, pretreatment with low concentrations of HOCl prevented
      phorbol myristate acetate-induced von Willebrand factor expression (a marker for
      P-selectin). These results show that, unlike H(2)O(2), HOCl does not
      significantly enhance neutrophil attachment to the endothelium. Rather it may be
      able to inhibit the expression of adhesion molecules with important consequences
      for endothelial function and inflammatory vascular disease.

PMID- 11970839
TI  - Ionomycin-induced neutrophil NADPH oxidase activity is selectively inhibited by
      the serine protease inhibitor diisopropyl fluorophosphate.
AB  - The calcium-specific ionophore ionomycin triggers neutrophils to activate their
      NADPH oxidase and generate reactive oxygen species. This activation is restricted
      to intracellular sites and involves the neutrophil granules. Cells that have
      experienced an ionomycin-induced rise in intracellular calcium will also mobilize
      their intracellular granules and are primed to subsequent challenge with the
      chemoattractant formylmethionyl-leucyl-phenylalanine (fMLF), but have lost their
      ability to become desensitized to the same agonist. We have investigated the
      involvement of serine proteases in the calcium-induced effector functions using
      the inhibitor diisopropyl fluorophosphate (DFP). The ionomycin-induced NADPH
      oxidase activity was abrogated by the protease inhibitor, whereas the activity
      induced by fMLF was unaffected. The DFP-dependent inhibition was restricted to
      the NADPH oxidase activity, as all other ionomycin-induced cellular activities
      were largely unaffected. We thus suggest that a serine protease is of importance
      for the calcium ionophore-induced signal(s) to reach and activate the dormant
      NADPH oxidase in the neutrophil granules.

PMID- 11970840
TI  - Antioxidant defense mechanisms in human neutrophils.
AB  - Neutrophils have a short half-life and high tendency to undergo apoptosis. One
      feature that may influence these characteristics is the antioxidant/oxidant
      balance of these cells. There are few studies on the levels of antioxidant
      enzymes in human neutrophils. We have analyzed by immunohistochemistry of
      paraffin-embedded cells and from cytospin preparations the most important
      antioxidant proteins in human neutrophils, and compared their levels with those
      in blood monocytes. Neutrophils showed moderate to high catalase, weak to
      moderate extracellular superoxide dismutase, and weak copper zinc superoxide
      dismutase and gamma-glutamylcysteine synthetase immunoreactivities. There were no
      detectable levels of manganese superoxide dismutase, thioredoxin, and heme
      oxygenase 1. Some differences were observed between the samples prepared by
      embedding in paraffin or by cytospin. These results, in combination with a recent
      study from this laboratory, suggest that a prominent feature in neutrophils is
      their high catalase activity but lower level of glutathione-dependent antioxidant
      enzymes. The differences in antioxidant profiles in neutrophils and monocytes may
      have important effects on the life span of human neutrophils, in both healthy and
      diseased tissues.

PMID- 11970841
TI  - The activity of leukocyte NADPH oxidase: regulation by p47PHOX cysteine and
      serine residues.
AB  - The leukocyte NADPH oxidase is regulated chiefly by phosphorylation of the
      serines of p47(PHOX), one of its cytosolic subunits. Its activity is also
      regulated, however, by the four cysteines of the same subunit, as indicated by
      the replacement of those cysteines by alanines.

PMID- 11970842
TI  - The signaling pathways induced by neutrophil-endothelial cell adhesion.
AB  - Adhesion of neutrophils to vascular endothelial cells (ECs), mediated by the
      interaction of CD11/CD18 and intercellular adhesion molecule-1 (ICAM-1), is often
      required for neutrophil transmigration across endothelium during most
      inflammatory responses. Induction of intracellular signaling in neutrophils as a
      result of adhesion has been recognized for many years. Recent studies
      demonstrated that neutrophil-endothelial adhesion also activates ECs. Examples of
      neutrophil adherence-induced changes in ECs include increases in intracellular
      Ca(2+), production of reactive oxygen species, and actin cytoskeleton changes.
      These changes result, in part, from ligation of EC adhesion molecules. This
      review article focuses on the signaling events that occur in ECs during
      neutrophil adhesion and the role of EC adhesion molecules, particularly ICAM-1,
      in the initiation of these signaling events in ECs. The evidence to date
      describing the molecular basis of ICAM-1-induced signaling will be summarized.
      Finally, the potential physiological roles of these signaling events induced by
      EC adhesion molecules in mediating neutrophil migration will be addressed.

PMID- 11970843
TI  - Assembly and activation of the neutrophil NADPH oxidase in granule membranes.
AB  - Phagocyte activation is accompanied by assembly of an NADPH oxidase that reduces
      oxygen to form a number of reactive species. These oxygen radicals can eradicate
      invading microorganisms, regulate the function of other immune reactive cells,
      and cause damage to "innocent bystander" cells. It is generally assumed that the
      NADPH oxidase is activated exclusively in the plasma membrane. In neutrophils,
      this assumption does not fit with the subcellular localization of the membrane
      component of the oxidase, which is stored in granule compartments. It has now
      become increasingly evident that oxidants are also produced in an intracellular
      compartment that we identify as the specific granules. Myeloperoxidase is stored
      in another granule subset, the azurophil granules, and participates in the
      processing of the oxidative metabolites. We suggest that neutrophil activation is
      accompanied by fusion between azurophil and specific granules, allowing these
      peroxidase-dependent reactions to take place. The presented data suggest a
      requisite role for neutrophil oxidants complementing their function as microbial
      killing agents. Signaling capabilities of the oxidants, affecting for example,
      the state of protein phosphorylation, regulation of transcription factors, and
      induction of apoptosis, are discussed.

PMID- 11970844
TI  - Modulation of the cytosolic and phagosomal pH by the NADPH oxidase.
AB  - Proton (equivalents) are primary participants in the control and potency of the
      NADPH oxidase. Both the cytosolic and intraphagosomal pH are influenced during
      oxidase activation, and maintenance of the optimal environment requires the
      coordinated action of a series of sophisticated, highly regulated H(+)
      transporters, including the Na(+)/H(+) exchange, vacuolar H(+)-ATPase, and H(+)
      conductive pathway(s). In addition, protons that are produced during some of the
      NADPH oxidase reactions then are substrates for the dismutation of superoxide,
      which precedes production of additional bactericidal agents. In this review, pH
      homeostasis is shown in conjunction with the NADPH oxidase to present an
      integrated picture of leukocyte physiology during the phagocytic response.

PMID- 11970845
TI  - Neutrophil priming in host defense: role of oxidants as priming agents.
AB  - Neutrophils play an essential role in the body's innate immune response to
      infection. To protect the host, these phagocytic cells possess an impressive
      array of microbicidal weapons that can be brought to bear on an invading
      pathogen, including a variety of toxic oxygen radical species and proteolytic
      enzymes. Although the neutrophil response is designed to restrict the damage to
      the smallest possible region where the pathogen is located, some of the damaging
      agents inevitably leak into the surrounding areas where they have the capacity to
      inflict tissue damage at sites of inflammation. Thus, it is essential that the
      host defense response of these cells is finely tuned to result in the appropriate
      level of response to any given situation. One of the regulatory mechanisms
      implicated in controlling neutrophil responses is priming. Through the action of
      priming agents, the level of activation and subsequent responses of the cell can
      be regulated so that a continuum of activation states is achieved. In this
      review, we describe key features of the priming response in host defense and
      disease pathogenesis and focus on the unique role of reactive oxygen species as
      priming agents.

PMID- 11970846
TI  - Redox regulation of Fcgamma receptor-mediated phagocytosis: implications for host
      defense and tissue injury.
AB  - Recent advances in our understanding of the mechanisms that regulate acute and
      chronic inflammatory responses have revealed a key role for reactive oxygen
      intermediates in modulating the activation of neutrophils. Opsonized microbes and
      immune complexes initiate the oxidative burst by the engagement of receptors for
      immunoglobulin G, termed Fcgamma receptors. The regulation of phagocytic cell
      function by oxidant-sensitive signaling pathways optimizes host defense
      capabilities, but it also amplifies tissue damage. This review will focus on the
      cross-talk between Fcgamma receptors and reactive oxygen intermediates at sites
      of inflammation and its role in microbial immunity.

PMID- 11970847
TI  - Redox regulation of neutrophil apoptosis.
AB  - The persistence of a neutrophil-mediated inflammatory response is due in part to
      a delay in their spontaneous rates of apoptosis or cell death. Regulating
      apoptosis has important implications for the resolution of inflammatory
      disorders, such as the systemic inflammatory response syndrome or acute
      respiratory distress syndrome. Neutrophils through their primary function of
      killing bacteria generate large concentrations of reactive oxygen intermediates
      and have alterations in the levels of antioxidants. Reactive oxygen intermediates
      and antioxidants are important regulators of the apoptotic caspases, but the
      mechanisms involved are still under debate and investigation. This review
      addresses the role of the cellular redox status of neutrophils on the apoptotic
      cascade leading to cell death.

PMID- 11970848
TI  - Trypanosomal antioxidants and emerging aspects of redox regulation in the
      trypanosomatids.
AB  - Leishmania and Trypanosoma are two genera of the protozoal Order Kinetoplastida
      that cause widespread diseases of humans and their livestock. The production of
      reactive oxygen and nitrogen intermediates by the host plays an important role in
      the control of infections by these organisms. Signal transduction and its redox
      regulation have not been studied in any depth in trypanosomatids, but homologs of
      the redox-sensitive signal transduction machinery of other eukaryotes have been
      recognized. These include homologs of activator protein-1, human apurinic
      endonuclease 1 (Ref-1) endonuclease, iron-responsive protein, protein kinases,
      and phosphatases. The detoxification of peroxide is catalyzed by a trypanothione
      dependent system that has no counterpart in mammals, and thus ranks as one of the
      biochemical peculiarities of trypanosomatids. There is substantial evidence that
      trypanothione is essential for the survival of Trypanosoma brucei and for the
      virulence of Leishmania spp. Apart from trypanothione and its precursors,
      trypanosomatids also possess significant amounts of N(1)-methyl-4
      mercaptohistidine or ovothiol A, but its function in the trypanosomatids is not
      presently understood. The biosynthesis of ovothiol A in Crithidia fasciculata
      proceeds by addition of sulfur from cysteine to histidine to form 4
      mercaptohistidine. S-(4'-L-Histidyl)-L-cysteine sulfoxide is the transsulfuration
      intermediate. 4-Mercaptohistidine is subsequently methylated with S
      adenosylmethionine as the likely methyl donor.

PMID- 11970849
TI  - Transcription factors regulating the response to oxidative stress in yeast.
AB  - A main avenue of defense against fungal infection uses oxidative killing of these
      and other microorganisms. Consequently, the ability of fungi to withstand an
      oxidative challenge has important implications for their ultimate pathogenicity
      in a host organism. Fungi also serve as an excellent model system for handling of
      reactive oxygen species in eukaryotic cells. For these reasons, a great deal of
      work has been invested in analyzing pathways involved in and the mechanisms
      regulating oxidative stress tolerance in fungi. The goal of this review is to
      discuss the current state of knowledge underlying the ability of fungal cells to
      mount a response to oxidative stress via activation of transcription factors.
      Studies in Saccharomyces cerevisiae have identified multiple transcriptional
      regulatory proteins that mediate tolerance to oxidative stress. Experiments
      focused on the fission yeast Schizosaccharomyces pombe have led to the discovery
      of protein kinase cascades highly related to mammalian stress-activated protein
      kinases. Recent studies on the pathogenic yeast Candida albicans have allowed
      analysis of the role of a critical oxidant-regulated transcription factor in this
      important human pathogen. Further understanding of oxidative stress resistance
      pathways in fungi is an important step toward understanding the molecular
      pathogenesis of these microorganisms.

PMID- 11970850
TI  - Reactive nitrogen and oxygen intermediates and bacterial defenses: unusual
      adaptations in Mycobacterium tuberculosis.
AB  - The production of reactive oxygen and reactive nitrogen intermediates is an
      important host defense mechanism mediated in response to infection by bacterial
      pathogens. Not surprisingly, intracellular pathogens have evolved numerous
      defense strategies to protect themselves against the damaging effects of these
      agents. In enteric bacteria, exposure to oxidative or nitrosative stress induces
      expression of numerous pathways that allow the bacterium to resist the toxic
      effects of these compounds during growth in the host. In contrast, members of
      pathogenic mycobacterial species, including the frank human pathogens
      Mycobacterium tuberculosis and Mycobacterium leprae, are dysfunctional in aspects
      of the oxidative and nitrosative stress response, yet they remain able to
      establish and maintain productive acute and persistent infections in the host.
      This article reviews the current knowledge regarding reactive oxygen and nitrogen
      intermediates, and compares the adaptative mechanisms utilized by enteric
      organisms and mycobacterial species to resist the bactericidal and bacteriostatic
      effects resulting from exposure to these compounds.

PMID- 11970851
TI  - Serum xanthine oxidase: origin, regulation, and contribution to control of
      trypanosome parasitemia.
AB  - African trypanosomiasis is caused by Salivarian trypanosomes, tsetse fly
      transmitted protozoa that inhabit the blood plasma, lymph and interstitial
      fluids, and, in the case of Trypanosoma brucei species, also the cerebrospinal
      fluid of mammal hosts. Trypanosomiasis in people and domestic animals manifests
      as recurring waves of parasites in the blood and is typically fatal. In contrast,
      trypanosomiasis in Cape buffaloes, which are naturally selected to resist the
      disease, is characterized by the development of only one or a few waves of
      parasitemia, after which the infection becomes cryptic, being maintained by the
      presence of 1-20 mammal-infective organisms/ml of blood. The control of the acute
      phase of parasitemia in Cape buffaloes correlates with a decline in blood
      catalase activity and the generation of trypanocidal H(2)O(2) in serum during the
      catabolism of endogenous purine by xanthine oxidase. Here we review features of
      this response, and of trypanosome metabolism, that facilitate H(2)O(2)-mediated
      killing of the parasites with minimal damage to the host. We also discuss the
      origin and regulation of serum xanthine oxidase and catalase, and show how
      recovery of serum catalase in infected Cape buffaloes precludes a role for
      H(2)O(2) in the long-term, stable suppression of trypanosome parasitemia.

PMID- 11970852
TI  - Redox signaling-mediated regulation of lipopolysaccharide-induced proinflammatory
      cytokine biosynthesis in alveolar epithelial cells.
AB  - The regulation of cytokine gene transcription and biosynthesis involves the
      reduction-oxidation (redox)-sensitive nuclear factor-kappaB (NF-kappaB), whose
      activation is mediated by an upstream kinase that regulates the phosphorylation
      of inhibitory-kappaB (IkappaB). It was hypothesized that lipopolysaccharide (LPS)
      induced biosynthesis of interleukin-1beta, interleukin-6, and tumor necrosis
      factor-alpha in vitro is regulated by redox equilibrium. In alveolar epithelial
      cells, we investigated the role of L-buthionine-(S,R)-sulfoximine (BSO), an
      irreversible inhibitor of gamma-glutamylcysteine synthetase, the rate-limiting
      enzyme in GSH biosynthesis, 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), which
      inhibits glutathione oxidized disulfide reductase, pyrrolidine dithiocarbamate
      (PDTC), an antioxidant/prooxidant thiuram, and N-acetyl-L-cysteine (NAC), an
      antioxidant and GSH precursor, in regulating LPS-induced cytokine biosynthesis
      and IkappaB-alpha/NF-kappaB signaling. BSO blockaded the phosphorylation of
      IkappaB-alpha, reduced its degradation, and inhibited NF-kappaB activation,
      besides augmenting LPS-mediated biosynthesis of cytokines. BCNU up-regulated LPS
      induced release of cytokines, an effect associated with partial
      phosphorylation/degradation of IkappaB-alpha and inhibition of the DNA binding
      activity. PDTC, which partially affected LPS-induced IkappaB-alpha
      phosphorylation/degradation, otherwise blockading NF-kappaB activation, reduced
      LPS-dependent up-regulation of cytokine release. Pretreatment with BSO did not
      abolish the NAC-dependent reduction of LPS-induced cytokine release, despite the
      fact that NAC marginally amplified IkappaB-alpha phosphorylation/degradation and
      suppressed NF-kappaB activation. These results indicate that cytokines are redox
      sensitive mediators and that the IkappaB-alpha/NF-kappaB pathway is redox
      sensitive and differentially implicated in mediating redox-dependent regulation
      of LPS-induced release of proinflammatory cytokines.

PMID- 11970853
TI  - alpha-Phenyl-N-tert-butylnitrone provides protection from dextran sulfate sodium
      induced colitis in mice.
AB  - Nuclear factor-kappaB (NF-kappaB)-dependent up-regulation of inflammatory
      cytokines and inducible nitric oxide (iNOS) occurs in inflammatory bowel disease.
      We investigated the effect of alpha-phenylN-tert-butylnitrone (PBN), a spin
      trapping agent that inhibits NF-kappaB activity, on dextran sulfate sodium (DSS)
      induced colonic mucosal injury and inflammation in mice. Acute colitis was
      induced with DSS in female BALB/c mice receiving 0, 0.3, 3, and 30 mg/kg i.p. PBN
      daily. Colonic mucosal inflammation was evaluated biochemically and
      histologically. Nitric oxide was evaluated as luminal nitrite/nitrite
      concentration by the Griess reaction and as immunoreactive nitrotyrosine in
      mucosal cells. Mucosal tumor necrosis factor-alpha (TNF-alpha) and interferon
      gamma (IFN-gamma) were determined by immunoassay. Colonic mRNA expression for
      iNOS, TNF-alpha, and IFN-gamma was measured by reverse transcription-polymerase
      chain reaction, and NF-kappaB activation was evaluated by electrophoretic
      mobility shift assay. After DSS administration, mice showed increased luminal
      nitrite/nitrate, mucosal TNF-alpha and IFN-gamma, and mRNA for iNOS and these
      cytokines, in addition to decreased colonic length and increased inflammatory
      score, luminal hemoglobin, and colonic myeloperoxidase activity. PBN inhibited
      increases in luminal nitric oxide production, nitrotyrosine immunoreactivity, and
      mucosal TNF-alpha and IFN-gamma. Colonic iNOS, TNF-alpha, and IFN-gamma mRNA were
      suppressed by PBN, as was a DSS-induced increase in colonic NF-kappaB DNA-binding
      activity. NF-kappaB is essential to DSS-induced colitis, suggesting molecular
      approach targeting of NF-kappaB for treatment of inflammatory bowel disease.

PMID- 11970854
TI  - Preferential inhibition of the plasma membrane NADH oxidase (NOX) activity by
      diphenyleneiodonium chloride with NADPH as donor.
AB  - The cell-surface NADH oxidase (NOX) protein of plant and animal cells will
      utilize both NADH and NADPH as reduced electron donors for activity. The two
      activities are distinguished by a differential inhibition by the redox inhibitor
      diphenyleneiodonium chloride (DPI). Using both plasma membranes and cells,
      activity with NADPH as donor was markedly inhibited by DPI at submicromolar
      concentrations, whereas with NADH as donor, DPI was much less effective or had no
      effect on the activity. The possibility of the inhibition being the result of two
      different enzymes was eliminated by the use of a recombinant NOX protein. The
      findings support the concept that NOX proteins serve as terminal oxidases for
      plasma membrane electron transport involving cytosolic reduced pyridine
      nucleotides as the natural electron donors and with molecular oxygen as the
      electron acceptor.

PMID- 11970855
TI  - Attenuation of the development of murine solid leukemia tumor by physical
      exercise.
AB  - The active involvement of physical exercise in the evolution of a variety of
      cancers is well documented. However, its role in solid leukemia tumor development
      is essentially unknown. Solid leukemia tumor cells were transplanted into 21
      hybrid BDF1 control mice, exercise-trained mice that did not exercise during
      leukemia and exercise-trained mice that exercised during leukemia. The tumor size
      of the continuously exercising group was ~50% of that of control and exercise
      terminated animals 18 days after the transplantation. The activity of antioxidant
      enzymes and the levels of lipid peroxidation and 8-hydroxy-2'-deoxyguanosine were
      not different in the tumors of the three groups. The level of carbonylated
      proteins was smaller in tumors of continuously exercising animals. The mutant
      form of cell regulatory protein p53 and vascular endothelial growth factor were
      present in similar amounts in the tumor cells of each group. On the other hand,
      the protooncogene Ras and I-kappaB proteins were present in higher concentrations
      in tumors of continuously exercising rats. The present data suggest that exercise
      during leukemia attenuates the development of tumors in mice. The selective
      alteration of regulatory proteins might play a role in the beneficial effects of
      exercise during leukemia.

PMID- 11970856
TI  - N-Acetylcysteine negatively modulates nitric oxide production in endotoxin
      treated rats through inhibition of NF-kappaB activation.
AB  - N-Acetylcysteine (NAC) has a wide spectrum of biological activities, either
      related to the ability to increase intracellular thiols or directly acting as an
      antioxidant. We used an in vivo animal model to study NAC modulation of nitric
      oxide (NO) production in response to lipopolysaccharide treatment. A comparison
      was made between NAC and the N-[3-(aminomethyl)benzyl] acetamidine (1400W), an
      inhibitor of the inducible NO synthase (iNOS). Both inhibit NO production,
      although NAC lacks any effect if given when iNOS is already induced; this
      indicates that the decrease of NO generation is not due to an effect on iNOS
      activity. We found that the DNA binding activity of nuclear transcription factor
      kappaB in peripheral blood cells was inhibited by NAC given before
      lipopolysaccharide, whereas tumor necrosis factor-alpha secretion was not
      affected.

PMID- 11970857
TI  - Signaling microdomains: InsP(3) receptor localization takes on new meaning.
AB  - A fundamental question in cell biology is how different receptor-mediated
      signaling cascades, despite utilizing many of the same intracellular components,
      can generate specific cellular responses. Delmas and colleagues (in this issue of
      Neuron) address this question in relation to the muscarinic acetylcholine
      receptor (M(1)AchR) and the B(2) bradykinin receptor (B(2)R). Using Trp channel
      isoforms as biosensors for PLC stimulation in response to agonist activation,
      they demonstrate a role for signaling microdomains in the induction of such
      selective responses.

PMID- 11970858
TI  - Have we been hebbing down the wrong path?
AB  - In this issue of Neuron, Stepanyants, Hof, and Chklovskii derive a simple
      mathematical formula to calculate, from measurable anatomical parameters, the
      capacity for neuronal wiring plasticity involving local synaptic rearrangements.
      Their work provides a deeper understanding of the potential contribution of
      structural plasticity to learning and memory.

PMID- 11970859
TI  - Neurons that program what to do and in what order.
AB  - In this issue of Neuron, describe the activity of single neurons in the SEF of
      monkeys, an oculomotor area of the frontal lobe, during the performance of
      stereotyped sequences of saccades. The monkey had to look at one of two identical
      stimuli, but the only way to choose the "correct" stimulus was to learn and
      remember its position in each presentation of the sequence. SEF neurons could do
      it.

PMID- 11970860
TI  - Dynamic multiphosphorylation passwords for activity-dependent gene expression.
AB  - Synapse-to-nucleus signaling leading to CREB-mediated transcription is important
      for neuronal plasticity. Nuclear CREB phosphorylation at Ser133 allows
      convergence of multiple kinase pathways driven by neuronal activity and links
      them to transcriptional activation. But, can various pathways share a common
      effector mechanism (phosphorylating Ser133) while generating distinct patterns of
      gene expression? We review three Neuron articles that highlight novel ways Ca(2+)
      signals can trigger multiple phosphorylation events working in combination to
      control CREB and its interaction with coactivator molecules.

PMID- 11970861
TI  - Posttranslational mechanisms control the timing of bHLH function and regulate
      retinal cell fate.
AB  - During central nervous system development, neurons are often born in a precise
      temporal sequence. Basic helix-loop-helix (bHLH) transcription factors are
      required for the development of specific subpopulations of neurons, but how they
      contribute to their ordered genesis is unclear. We show that the ability of bHLH
      factors to regulate the development of distinct neuronal subtypes in the Xenopus
      retina depends upon the timing of their function. In addition, we find that the
      timing of bHLH function can be regulated posttranslationally, so that bHLH
      factors with overlapping expression can function independently. Specifically,
      XNeuroD function in the retina can be inhibited by glycogen synthase kinase 3beta
      (GSK3beta), while Xath5 function can be inhibited by Notch. Thus, the potential
      of bHLH factors to regulate the development of neuronal subtypes depends upon the
      context in which they function.

PMID- 11970862
TI  - An intersubunit interaction regulates trafficking of rod cyclic nucleotide-gated
      channels and is disrupted in an inherited form of blindness.
AB  - A mutation in a cyclic nucleotide-gated channel (CNGA1) is associated with
      retinitis pigmentosa (RP), a common, inherited eye disease. Expression of mutant
      (CNGA1-RP) homomeric channels in Xenopus oocytes revealed no measurable
      differences compared to wild-type CNGA1 homomers. As native retinal rod CNG
      channels comprise CNGA1 and CNGB1 subunits, we coexpressed CNGA1-RP and CNGB1.
      Surprisingly, this subunit combination did not produce detectable channels at the
      membrane surface. We show that the mechanism underlying this defect involves an
      intersubunit interaction between CNGA1 and CNGB1 that was not formed between
      CNGA1-RP and CNGB1 subunits. In the absence of this interaction, a short N
      terminal region in CNGB1 prevented membrane expression. Thus, disruption of a
      regulatory interaction by mutation in CNGA1 exposed a region of CNGB1 that
      disrupted surface expression of heteromeric CNGA1-RP/CNGB1 channels, accounting
      for this instance of RP.

PMID- 11970863
TI  - Signaling microdomains define the specificity of receptor-mediated InsP(3)
      pathways in neurons.
AB  - M(1) muscarinic (M(1)AChRs) and B(2) bradykinin (B(2)Rs) receptors are two
      PLCbeta-coupled receptors that mobilize Ca(2+) in nonexcitable cells. In many
      neurons, however, B(2)Rs but not M(1)AChRs mobilize intracellular Ca(2+). We have
      studied the membrane organization and dynamics underlying this coupling
      specificity by using Trp channels as biosensors for real-time detection of
      PLCbeta products. We found that, in sympathetic neurons, although both receptors
      rapidly produced DAG and InsP(3) as messengers, only InsP(3) formed by B(2)Rs has
      the ability to activate IP(3)Rs. This exclusive coupling results from spatially
      restricted complexes linking B(2)Rs to IP(3)Rs, a missing partnership for
      M(1)AChRs. These complexes allow fast and localized rises of InsP(3), necessary
      to activate the low-affinity neuronal IP(3)R. Thus, these signaling microdomains
      are of critical importance for the induction of selective responses,
      discriminating proinflammatory information associated with B(2)Rs from
      cholinergic neurotransmission.

PMID- 11970864
TI  - CREB transcriptional activity in neurons is regulated by multiple, calcium
      specific phosphorylation events.
AB  - The transcription factor CREB mediates diverse responses in the nervous system.
      It is not known how CREB induces specific patterns of gene expression in response
      to different extracellular stimuli. We find that Ca(2+) influx into neurons
      induces CREB phosphorylation at Ser133 and two additional sites, Ser142 and
      Ser143. While CREB Ser133 phosphorylation is induced by many stimuli,
      phosphorylation at Ser142 and Ser143 is selectively activated by Ca(2+) influx.
      The triple phosphorylation of CREB is required for effective Ca(2+) stimulation
      of CREB-dependent transcription, but the phosphorylation of Ser142 and Ser143, in
      addition to Ser133, disrupts the interaction of CREB with its cofactor CBP. These
      results suggest that Ca(2+) influx triggers a specific program of gene expression
      in neurons by selectively regulating CREB phosphorylation.

PMID- 11970866
TI  - Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the
      circadian clock.
AB  - Biological rhythms are driven in mammals by a central circadian clock located in
      the suprachiasmatic nucleus (SCN). Light-induced phase shifting of this clock is
      correlated with phosphorylation of CREB at Ser133 in the SCN. Here, we
      characterize phosphorylation of CREB at Ser142 and describe its contribution to
      the entrainment of the clock. In the SCN, light and glutamate strongly induce
      CREB Ser142 phosphorylation. To determine the physiological relevance of
      phosphorylation at Ser142, we generated a mouse mutant, CREB(S142A), lacking this
      phosphorylation site. Light-induced phase shifts of locomotion and expression of
      c-Fos and mPer1 in the SCN are significantly attenuated in CREB(S142A) mutants.
      Our findings provide genetic evidence that CREB Ser142 phosphorylation is
      involved in the entrainment of the mammalian clock and reveal a novel
      phosphorylation-dependent regulation of CREB activity.

PMID- 11970865
TI  - Phosphorylation of CBP mediates transcriptional activation by neural activity and
      CaM kinase IV.
AB  - Activity-regulated transcription has been implicated in adaptive plasticity in
      the CNS. In many instances, this plasticity depends upon the transcription factor
      CREB. Precisely how neuronal activity regulates CREB remains unclear. To address
      this issue, we examined the phosphorylation state of components of the CREB
      transcriptional pathway. We show that NMDA activates transcription of CREB
      responsive genes in hippocampal neurons, with ERK responsible for persistent CREB
      phosphorylation and CaM kinase IV (CaMKIV) responsible for phosphorylating the
      CREB coactivator, CBP. Ser301 of CBP was identified as a major target of CaMKIV
      phosphorylation in vitro and in vivo. CaM kinase inhibitors attenuated
      phosphorylation at Ser301 and blocked CBP-dependent transcription. Additionally,
      mutation of Ser301 impaired NMDA- and CaMKIV-stimulated transcription. These
      findings demonstrate that activity-induced CaMKIV signaling contributes to
      CREB/CBP-dependent transcription by phosphorylating CBP at Ser301.

PMID- 11970867
TI  - Mobile NMDA receptors at hippocampal synapses.
AB  - Glutamate receptors are concentrated in the postsynaptic complex of central
      synapses. This implies a highly organized and stable postsynaptic membrane with
      tightly anchored receptors. Recent reports of rapid AMPA receptor insertion and
      removal at synapses have challenged this view. We examined the stability of
      synaptic NMDA receptors on cultured hippocampal neurons using the open-channel
      blockers (+)-MK-801 and ketamine to tag synaptic NMDA receptors. NMDA receptor
      mediated EPSCs showed an anomalous recovery following "irreversible" MK-801
      block. The recovery could not be attributed to MK-801 unbinding or insertion of
      new receptors, suggesting that membrane receptors had moved laterally into the
      synapse. At least 65% of synaptic NMDA receptors were mobile. Our results
      indicate that NMDA receptors can move laterally between synaptic and
      extrasynaptic pools, providing evidence for a dynamic organization of synaptic
      NMDA receptors in the postsynaptic complex.

PMID- 11970868
TI  - Formation of dendritic spines with GABAergic synapses induced by whisker
      stimulation in adult mice.
AB  - During development, alterations in sensory experience modify the structure of
      cortical neurons, particularly at the level of the dendritic spine. Are similar
      adaptations involved in plasticity of the adult cortex? Here we show that a 24 hr
      period of single whisker stimulation in freely moving adult mice increases, by
      36%, the total synaptic density in the corresponding cortical barrel. This is due
      to an increase in both excitatory and inhibitory synapses found on spines. Four
      days after stimulation, the inhibitory inputs to the spines remain despite total
      synaptic density returning to pre-stimulation levels. Functional analysis of
      layer IV cells demonstrated altered response properties, immediately after
      stimulation, as well as four days later. These results indicate activity
      dependent alterations in synaptic circuitry in adulthood, modifying the flow of
      sensory information into the cerebral cortex.

PMID- 11970869
TI  - Geometry and structural plasticity of synaptic connectivity.
AB  - Changes in synaptic connectivity patterns through the formation and elimination
      of dendritic spines may contribute to structural plasticity in the brain. We
      characterize this contribution quantitatively by estimating the number of
      different synaptic connectivity patterns attainable without major arbor
      remodeling. This number depends on the ratio of the synapses on a dendrite to the
      axons that pass within a spine length of that dendrite. We call this ratio the
      filling fraction and calculate it from geometrical analysis and anatomical data.
      The filling fraction is 0.26 in mouse neocortex, 0.22-0.34 in rat hippocampus. In
      the macaque visual cortex, the filling fraction increases by a factor of 1.6-1.8
      from area V1 to areas V2, V4, and 7a. Since the filling fraction is much smaller
      than 1, spine remodeling can make a large contribution to structural plasticity.

PMID- 11970870
TI  - Fear conditioning occludes LTP-induced presynaptic enhancement of synaptic
      transmission in the cortical pathway to the lateral amygdala.
AB  - Auditory information critical for fear conditioning, a model of emotional
      learning, is conveyed to the lateral nucleus of the amygdala via two routes:
      directly from the medial geniculate nucleus and indirectly from the auditory
      cortex. Here we show in the cortico-amygdala pathway that learned fear occludes
      electrically induced long-term potentiation (LTP). Quantal analysis of the
      expression of LTP in this pathway reveals a significant presynaptic component
      reflected in an increase in probability of transmitter release. Conditioned fear
      also is accompanied by the enhancement in transmitter release at this cortico
      amygdala synapse. These results indicate that the synaptic projections from the
      auditory cortex to the lateral amygdala are modified during the acquisition and
      expression of fear to auditory stimulation, thus further strengthening the
      proposed link between LTP in the auditory pathways to the amygdala and learned
      fear.

PMID- 11970871
TI  - Spatio-temporal dynamics of odor representations in the mammalian olfactory bulb.
AB  - We explored the spatio-temporal dynamics of odor-evoked activity in the rat and
      mouse main olfactory bulb (MOB) using voltage-sensitive dye imaging (VSDI) with a
      new probe. The high temporal resolution of VSDI revealed odor-specific sequences
      of glomerular activation. Increasing odor concentrations reduced response
      latencies, increased response amplitudes, and recruited new glomerular units.
      However, the sequence of glomerular activation was maintained. Furthermore, we
      found distributed MOB activity locked to the nasal respiration cycle. The spatial
      distribution of its amplitude and phase was heterogeneous and changed by sensory
      input in an odor-specific manner. Our data show that in the mammalian olfactory
      bulb, odor identity and concentration are represented by spatio-temporal
      patterns, rather than spatial patterns alone.

PMID- 11970872
TI  - A neural correlate of oculomotor sequences in supplementary eye field.
AB  - Complex learned motor sequences can be composed of a combination of a small
      number of elementary actions. To investigate how the brain represents such
      sequences, we devised an oculomotor sequence task in which the monkey had to
      choose the target solely by the sequential context, not by the current stimulus
      combination. We found that many neurons in the supplementary eye field (SEF)
      became active with a specific target direction (D neuron) or a specific
      target/distractor combination (C neuron). Furthermore, such activity was often
      selective for one among several sequences that included the combination (S
      neuron). These results suggest that the SEF contributes to the generation of
      saccades in many learned sequences.

PMID- 11970873
TI  - Live and let die: Nef functions beyond HIV replication.
AB  - The viral Nef protein is important for the progression of the human and simian
      immunodeficiency virus (HIV/SIV) infection. So far, experimental evidence has
      suggested that Nef enhances viral replication and infectivity through a
      combination of different effects. Recent insights, however, indicate that its
      functions are more complex than previously anticipated. By targeting the T cell
      receptor, Nef may not only prime viral replication but, more importantly, ensure
      viral survival through distinct mechanisms of immune evasion and antiapoptosis.

PMID- 11970874
TI  - Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome.
AB  - This study addresses the biological function of the p53-effector genes Gadd45a
      and p21 in the immune system. We find that Gadd45a is a negative regulator of T
      cell proliferation because, compared to wild-type cells, Gadd45a(-/-) T cells
      have a lower threshold of activation and proliferate to a greater extent
      following primary T cell receptor stimulation. Gadd45a(-/-) mice develop an
      autoimmune disease, similar to human systemic lupus erythematosus (SLE),
      characterized by high titers of anti-dsDNA, anti-ssDNA, and anti-histone
      autoantibodies, severe hematological disorders, autoimmune glomerulonephritis,
      and premature death. Here we show that the lack of both Gadd45a and p21
      dramatically accelerates the development of autoimmunity observed in each
      individual single-gene disruption mutant, demonstrating that these genes play
      nonredundant roles in the immune response.

PMID- 11970875
TI  - Optimization of the MHC class I peptide cargo is dependent on tapasin.
AB  - The loading of MHC class I molecules with their peptide cargo is undertaken by a
      multimolecular peptide loading complex within the endoplasmic reticulum. We show
      that MHC class I molecules can optimize their peptide repertoire over time and
      that this process is dependent on tapasin. Optimization of the peptide repertoire
      is both quantitatively and qualitatively improved by tapasin. The extent of
      optimization is maximal when MHC class I molecules are allowed to load within the
      fully assembled peptide loading complex. Finally, we identify a single natural
      polymorphism (116D>Y) in HLA-B*4402 that permits tapasin-independent loading of
      HLA-B*4405 (116Y). In the presence of tapasin, the tapasin-independent allele
      B*4405 (116Y) acquires a repertoire of peptides that is less optimal than the
      tapasin-dependent allele B*4402 (116D).

PMID- 11970876
TI  - Inhibition of T cell receptor-coreceptor interactions by antagonist ligands
      visualized by live FRET imaging of the T-hybridoma immunological synapse.
AB  - The diverse effects of TCR agonists and antagonists on T cell activation are
      believed to be modified by the differential recruitment of CD4 or CD8 coreceptors
      to the TCR-MHCp complex. We used three-dimensional live cell imaging of
      fluorescence resonance energy transfer (FRET) between CD3zeta and CD4 fused to
      variants of the green fluorescent protein to investigate TCR-CD4 interactions
      during T cell activation. We demonstrate that recognition of agonist MHCp
      complexes triggers intermolecular interaction between CD4 and TCR, detectable
      across the T-hybridoma-APC contact area. This interaction is blocked by the
      presence of antagonist ligands without decreasing the recruitment of zeta and CD4
      or preventing their partial colocalization in the immunological synapse.

PMID- 11970877
TI  - The impact of T helper and T regulatory cells on the regulation of anti-double
      stranded DNA B cells.
AB  - Autoreactive B cells that appear to be inactivated can be found in healthy
      individuals. In this study, we examined the potential of these anergic cells to
      become activated. We show that anergy of anti-double-stranded DNA (dsDNA) B cells
      in BALB/c mice is readily reversed, requiring only the provision of T cell help.
      We further show that spontaneous loss of anergy among anti-dsDNA B cells in
      autoimmune lpr/lpr mice occurs in two phases: an abortive initial response to T
      help followed by full loss of tolerance. Strikingly, the abortive response can be
      reproduced in nonautoimmune mice when CD4+CD25+ T regulatory cells are
      administered in conjunction with CD4+ T helper cells, suggesting that loss of B
      cell tolerance may require both the production of T cell help and the overcoming
      of T suppression.

PMID- 11970878
TI  - Syk is required for integrin signaling in neutrophils.
AB  - The Syk tyrosine kinase plays a critical role in the signaling machinery of
      various receptors of the adaptive immune system. Here we show that Syk is also an
      essential component of integrin signaling in neutrophils. syk(-/-) neutrophils
      failed to undergo respiratory burst, degranulation, or spreading in response to
      proinflammatory stimuli while adherent to immobilized integrin ligands or when
      stimulated by direct crosslinking of integrins. Signaling from the beta(1),
      beta(2), or beta(3) integrins was defective in syk(-/-) cells. Syk colocalized
      with CD18 during cell spreading and initiated downstream signaling events leading
      to actin polymerization. Surprisingly, these defects in integrin-mediated
      activation did not impair the integrin-dependent in vitro or in vivo migration of
      syk(-/-) neutrophils or of cells deficient in Src-family kinases. Thus, integrins
      use different signaling mechanisms to support migration and adherent activation.

PMID- 11970879
TI  - IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a
      mediator of the transition from innate to adaptive immunity.
AB  - IFNalpha/beta, IL-12, and IL-15 regulate NK cell activation and expansion, but
      signals triggering resolution of the NK response upon induction of adaptive
      immunity remain to be defined. We now report that IL-21, a product of activated T
      cells, may serve this function. Mice lacking IL-21R (IL-21R(-/-)) had normal NK
      cell development but no detectable responses to IL-21. IL-21 enhanced cytotoxic
      activity and IFNgamma production by activated murine NK cells but did not support
      their viability, thus limiting their duration of activation. Furthermore, IL-21
      blocked IL-15-induced expansion of resting NK cells, thus preventing the
      initiation of further innate responses. In contrast, IL-21 enhanced the
      proliferation, IFNgamma production, and cytotoxic function of CD8(+) effector T
      cells in an allogeneic MLR. These observations suggest that IL-21 promotes the
      transition between innate and adaptive immunity.

PMID- 11970880
TI  - Hypermutation in shark immunoglobulin light chain genes results in contiguous
      substitutions.
AB  - Among 631 substitutions present in 90 nurse shark immunoglobulin light chain
      somatic mutants, 338 constitute 2-4 bp stretches of adjacent changes. An absence
      of mutations in perinatal sequences and the bias for one mutating V gene in
      adults suggest that the diversification is antigen dependent. The substitutions
      shared no patterns, and the absence of donor sequences, including from family
      members, supports the idea that most changes arose from nontemplated mutation.
      The tandem mutations as a group are distinguished by consistently fewer
      transition changes and an A bias. We suggest this is one of several pathways of
      hypermutation diversifying shark antigen-receptor genes--point mutations, tandem
      mutations, and mutations with a G-C preference--that coevolved with or preceded
      gene rearrangement.

PMID- 11970881
TI  - Activation of a nonclassical NKT cell subset in a transgenic mouse model of
      hepatitis B virus infection.
AB  - NKT cells are specialized cells of the immune system that bear both T cell and NK
      cell markers. Classical NKT cells display TCRs of restricted heterogeneity
      (Valpha14-Jalpha281) and recognize lipid antigens (e.g., alpha-galactosyl
      ceramide) presented by nonpolymorphic CD1 molecules. Recently, other nonclassical
      NKT subsets have been recognized, including NKT cells not reactive with CD1d
      alpha-galactosyl ceramide complexes. The biological functions of these cells are
      unknown. Here, we show that nonclassical NKT cells that are CD1d restricted but
      nonreactive to alpha-GalCer are activated in response to hepatocytes expressing
      hepatitis B viral antigens in a transgenic mouse model of acute hepatitis B virus
      infection. Our results document the first in vivo function for such nonclassical
      NKT cells and suggest a role for these cells in the host response to HBV
      infection.

PMID- 11970882
TI  - Imaging synapse formation during thymocyte selection: inability of CD3zeta to
      form a stable central accumulation during negative selection.
AB  - TCR signaling can result in cell fates ranging from activation to tolerance to
      apoptosis. Organization of molecules in an "immunological synapse" between mature
      T cells and APCs correlates with the strength of TCR signaling. To investigate
      synapse formation during thymic selection, we have established a reaggregate
      system in which molecular recruitment of GFP fusion proteins to thymocyte:stromal
      cell interfaces can be visualized in real time. We demonstrate that negative
      selection is associated with efficient conjugate formation and rapid recruitment
      of p56(lck) and CD3zeta to an immunological synapse. Interestingly, CD3zeta-GFP
      does not accumulate at the center of the synapse, as in mature T cells, but at
      the periphery across a wide range of ligand densities. This implicates
      differences in synapse geometry in initiation of alternate signals downstream of
      the TCR.

PMID- 11970883
TI  - IgH class switch recombination to IgG1 in DNA-PKcs-deficient B cells.
AB  - To assess the role of the DNA-PKcs nonhomologous DNA end-joining (NHEJ) protein
      in Ig heavy chain class switch recombination (CSR), we assayed CSR ability of DNA
      PKcs-deficient (DP-T) B cells generated via complementation of DP-T mice with Ig
      heavy chain and light chain knock-in transgenes (DP-T/HC/LC mice). DP-T/HC/LC
      mice were severely deficient for all serum IgH isotypes except IgM and,
      unexpectedly, IgG1. Upon appropriate stimulation, DP-T/HC/LC B cells showed
      normal proliferation, germline C(H) gene transcription, and AID induction,
      indicating that DNA-PKcs deficiency did not affect cellular events upstream to
      CSR. Yet, in vitro activated DP-T/HC/LC B cells again underwent switching only to
      IgG1 and, like wild-type cells, frequently underwent CSR to gamma1 on both
      chromosomes. We conclude that DNA-PKcs is required for CSR to most C(H) genes but
      that CSR to gamma1 occurs via a DNA-PKcs-independent mechanism.

PMID- 11970884
TI  - Vesicle tethers promoting fusion machinery assembly.
AB  - In a recent issue of the Journal of Cell Biology, Shorter et al. demonstrate that
      p115, a vesicle tethering protein, binds specific SNAREs, key components of the
      membrane fusion machinery, and uncover that this interaction promotes the
      assembly of the fusion machinery.

PMID- 11970885
TI  - Why FRET about Ran?
AB  - The Ran GTPase drives nucleocytoplasmic transport, stabilizes mitotic spindles,
      and catalyzes nuclear envelope formation. A unifying explanation of these
      functions is that RanGTP produces an organizing field or "atmosphere" around
      chromatin and acts as a spatial marker. This RanGTP field has now been visualized
      using fluorescent biosensors.

PMID- 11970886
TI  - Chromosome segregation: playing polo in prophase.
AB  - During mitosis, in most eukaryotes, cohesin is removed from chromosomes in two
      steps. A paper in the March issue of Molecular Cell identifies Polo-like kinase
      as a key regulator for the first step that releases much of cohesin during
      prophase.

PMID- 11970887
TI  - Cellular morphogenesis: slow-as-molasses accelerates polarized membrane growth.
AB  - Cellularization of the early Drosophila embryo is a modified form of cytokinesis
      that gives rise to the blastoderm epithelium through polarized membrane growth.
      The gene slow-as-molasses encodes a novel protein essential for the formation of
      a plasma membrane domain that initiates membrane growth during cellularization.

PMID- 11970888
TI  - Signal transduction in development: holding the key.
AB  - The unrelated GSK-3 and CK1 families stand out among the protein kinases because
      of their phosphorylated substrate recognition sites. Two papers in the March 22nd
      issue of Cell highlight the importance of this priming phosphorylation for signal
      transduction during development.

PMID- 11970889
TI  - Protein tyrosine phosphatase 1B: a potential leptin resistance factor of obesity.
AB  - Indirect evidence implicates leptin resistance in the pathogenesis of the
      lipotoxicity that complicates obesity and results in the metabolic syndrome. In
      this issue of Developmental Cell, two groups identify protein tyrosine
      phosphatase 1B (PTP1B) as a cause of leptin resistance through dephosphorylation
      of Jak2.

PMID- 11970890
TI  - Reaching a genetic and molecular understanding of skeletal development.
AB  - In the last ten years, we have made considerable progress in our genetic and
      molecular understanding of all aspects of skeletal development, chondrogenesis,
      joint formation, and osteogenesis. This review addresses the role of the
      principal growth factors and transcription factors affecting these different
      processes and presents, in several cases, the genetic cascade leading to cell
      differentiation.

PMID- 11970891
TI  - Lipid research picks up speed on the slopes of Taos.
AB  - The 2002 Keystone Symposium on "Regulation of Cellular Responses by Lipid
      Mediators" provided a lively and active forum to discuss research in lipid
      signaling. This meeting review can provide only a glimpse into the diversity of
      research presented. Here we have chosen to highlight a group of exciting
      presentations describing novel features of the temporal and spatial regulation of
      phosphoinositides and their downstream targets.

PMID- 11970892
TI  - GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42
      regulated, clathrin-independent pinocytic pathway.
AB  - Endocytosis of cell-surface proteins via specific pathways is critical for their
      function. We show that multiple glycosylphosphatidylinositol-anchored proteins
      (GPI-APs) are endocytosed to the recycling endosomal compartment but not to the
      Golgi via a nonclathrin, noncaveolae mediated pathway. GPI anchoring is a
      positive signal for internalization into rab5-independent tubular-vesicular
      endosomes also responsible for a major fraction of fluid-phase uptake; molecules
      merely lacking cytoplasmic extensions are not included. Unlike the
      internalization of detergent-resistant membrane (DRM)-associated interleukin 2
      receptor, endocytosis of DRM-associated GPI-APs is unaffected by inhibition of
      RhoA or dynamin 2 activity. Inhibition of Rho family GTPase cdc42, but not Rac1,
      reduces fluid-phase uptake and redistributes GPI-APs to the clathrin-mediated
      pathway. These results describe a distinct constitutive pinocytic pathway,
      specifically regulated by cdc42.

PMID- 11970893
TI  - slam encodes a developmental regulator of polarized membrane growth during
      cleavage of the Drosophila embryo.
AB  - Cellularization of the Drosophila embryo is a specialized form of cytokinesis
      that couples membrane growth with the formation of a polarized epithelium. We
      have identified a gene essential for polarized growth of the plasma membrane
      during cellularization. In slam mutant embryos, the furrow canal is disorganized,
      and polarized insertion of transmembrane proteins is disrupted. slam shows a
      striking developmental induction during the slow phase of cellularization, and
      Slam protein localizes to the furrow canal and the basal junction. Slam
      colocalizes with the junctional proteins Arm/beta-catenin, the PDZ domain
      containing protein Dlt, and Myosin and is also required for their proper membrane
      localization. Our results suggest that developmental induction of Slam organizes
      the polarized growth of membrane via the recruitment of membrane-targeting
      proteins at adherens junctions.

PMID- 11970894
TI  - DWnt4 regulates cell movement and focal adhesion kinase during Drosophila ovarian
      morphogenesis.
AB  - Cell motility is regulated by extracellular cues and by intracellular factors
      that accumulate at sites of contact between cells and the extracellular matrix.
      One of these factors, focal adhesion kinase (FAK), regulates the cycle of focal
      adhesion formation and disassembly that is required for cell movement to occur.
      Recently, Wnt signaling has also been implicated in the control of cell movement
      in vertebrates, but the mechanism through which Wnt proteins influence motility
      is unclear. We demonstrate that Drosphila Wnt4 is required for cell movement and
      FAK regulation during ovarian morphogenesis. Dfrizzled2, Disheveled, and protein
      kinase C are also required. The DWnt4 cell motility pathway is distinct from both
      the canonical Wnt pathway and the planar polarity pathway. Our data suggest that
      DWnt4 facilitates motility through regulation of focal adhesions.

PMID- 11970895
TI  - Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is
      required for notochord formation.
AB  - Dapper was isolated in a screen for proteins interacting with Dishevelled, a key
      factor in Wnt signaling. Dapper and Dishevelled colocalize intracellularly and
      form a complex with Axin, GSK-3, CKI, and beta-catenin. Overexpression of Dapper
      increases Axin and GSK-3 in this complex, resulting in decreased soluble beta
      catenin and decreased activation of beta-catenin-responsive genes. Dapper also
      inhibits activation by Dishevelled of c-Jun N-terminal kinase (JNK), a component
      of beta-catenin-independent Frizzled signaling. Inhibition of Dapper activates
      both beta-catenin-responsive genes and an AP1-responsive promoter, demonstrating
      that Dapper is a general Dishevelled antagonist. Depletion of maternal Dapper RNA
      from Xenopus embryos results in loss of notochord and head structures,
      demonstrating that Dapper is required for normal vertebrate development.

PMID- 11970896
TI  - CENP-I is essential for centromere function in vertebrate cells.
AB  - We identified a novel essential centromere protein, CENP-I, which shows sequence
      similarity with fission yeast Mis6 protein, and we showed that CENP-I is a
      constitutive component of the centromere that colocalizes with CENP-A, -C, and -H
      throughout the cell cycle in vertebrate cells. To determine the precise function
      of CENP-I, we examined its role in centromere function by generating a
      conditional loss-of-function mutant in the chicken DT40 cell line. In the absence
      of CENP-I, cells arrested at prometaphase with misaligned chromosomes for long
      periods of time. Eventually, cells exited mitosis without undergoing cytokinesis.
      Immunocytochemical analysis of CENP-I-deficient cells demonstrated that both CENP
      I and CENP-H are necessary for localization of CENP-C but not CENP-A to the
      centromere.

PMID- 11970897
TI  - Insulin causes fatty acid transport protein translocation and enhanced fatty acid
      uptake in adipocytes.
AB  - Fatty acid uptake into 3T3 L1 adipocytes is predominantly transporter mediated.
      Here we show that, during 3T3 L1 adipocyte differentiation, expression of fatty
      acid transport proteins (FATPs) 1 and 4 is induced. Using subcellular membrane
      fractionation and immunofluorescence microscopy, we demonstrate that, in
      adipocytes, insulin induces plasma membrane translocation of FATPs from an
      intracellular perinuclear compartment to the plasma membrane. This translocation
      was observed within minutes of insulin treatment and was paralleled by an
      increase in long chain fatty acid (LCFA) uptake. In contrast, treatment with TNF
      alpha inhibited basal and insulin-induced LCFA uptake and reduced FATP1 and -4
      levels. Thus, hormonal regulation of FATP activity may play an important role in
      energy homeostasis and metabolic disorders such as type 2 diabetes.

PMID- 11970898
TI  - PTP1B regulates leptin signal transduction in vivo.
AB  - Mice lacking the protein-tyrosine phosphatase PTP1B are hypersensitive to insulin
      and resistant to obesity. However, the molecular basis for resistance to obesity
      has been unclear. Here we show that PTP1B regulates leptin signaling. In
      transfection studies, PTP1B dephosphorylates the leptin receptor-associated
      kinase, Jak2. PTP1B is expressed in hypothalamic regions harboring leptin
      responsive neurons. Compared to wild-type littermates, PTP1B(-/-) mice have
      decreased leptin/body fat ratios, leptin hypersensitivity, and enhanced leptin
      induced hypothalamic Stat3 tyrosyl phosphorylation. Gold thioglucose treatment,
      which ablates leptin-responsive hypothalamic neurons, partially overcomes
      resistance to obesity in PTP1B(-/-) mice. Our data indicate that PTP1B regulates
      leptin signaling in vivo, likely by targeting Jak2. PTP1B may be a novel target
      to treat leptin resistance in obesity.

PMID- 11970899
TI  - Attenuation of leptin action and regulation of obesity by protein tyrosine
      phosphatase 1B.
AB  - Common obesity is primarily characterized by resistance to the actions of the
      hormone leptin. Mice deficient in protein tyrosine phosphatase 1B (PTP1B) are
      resistant to diabetes and diet-induced obesity, prompting us to further define
      the relationship between PTP1B and leptin in modulating obesity. Leptin-deficient
      (Lep(ob/ob)) mice lacking PTP1B exhibit an attenuated weight gain, a decrease in
      adipose tissue, and an increase in resting metabolic rate. Furthermore, PTP1B
      deficient mice show an enhanced response toward leptin-mediated weight loss and
      suppression of feeding. Hypothalami from these mice also display markedly
      increased leptin-induced Stat3 phosphorylation. Finally, substrate-trapping
      experiments demonstrate that leptin-activated Jak2, but not Stat3 or the leptin
      receptor, is a substrate of PTP1B. These results suggest that PTP1B negatively
      regulates leptin signaling, and provide one mechanism by which it may regulate
      obesity.

PMID- 11970900
TI  - Nuclear-localized BZR1 mediates brassinosteroid-induced growth and feedback
      suppression of brassinosteroid biosynthesis.
AB  - Plant steroid hormones, brassinosteroids (BRs), are perceived by a cell surface
      receptor kinase, BRI1, but how BR binding leads to regulation of gene expression
      in the nucleus is unknown. Here we describe the identification of BZR1 as a
      nuclear component of the BR signal transduction pathway. A dominant mutation bzr1
      1D suppresses BR-deficient and BR-insensitive (bri1) phenotypes and enhances
      feedback inhibition of BR biosynthesis. BZR1 protein accumulates in the nucleus
      of elongating cells of dark-grown hypocotyls and is stabilized by BR signaling
      and the bzr1-1D mutation. Our results demonstrate that BZR1 is a positive
      regulator of the BR signaling pathway that mediates both downstream BR responses
      and feedback regulation of BR biosynthesis.

PMID- 11970901
TI  - Hepatocyte growth factor: the key to alveolar septation?

PMID- 11970902
TI  - Regulators of telomerase activity.

PMID- 11970903
TI  - Hepatocyte growth factor stimulates proliferation of respiratory epithelial cells
      during postpneumonectomy compensatory lung growth in mice.
AB  - Although it is known that the lung undergoes compensatory growth after pulmonary
      resection, mechanisms by which lung cells exhibit compensatory proliferation are
      not well defined. We investigated the involvement of hepatocyte growth factor
      (HGF) in postpneumonectomy compensatory lung regeneration in mice, because HGF
      has mitogenic and morphogenic actions on lung epithelial cells. Following left
      pneumonectomy, alveolar and airway epithelial cells underwent compensatory DNA
      synthesis, reaching maximal levels 5 d after the surgery. Before changes in DNA
      synthesis in lung epithelial cells, expression of HGF mRNA and protein levels in
      the remaining lung, liver, and kidney were changed in response to left
      pneumonectomy, and these changes were associated with postoperative increases in
      plasma HGF levels. c-Met/HGF receptor expression was localized predominantly in
      alveolar type II and airway epithelial cells, whereas c-Met/HGF receptor mRNA
      expressions were transiently upregulated before the peak in lung DNA synthesis.
      Neutralization of endogenous HGF by an antibody in pneumonectomized mice
      suppressed the compensatory DNA synthesis in lung epithelial cells, whereas
      administration of recombinant HGF to pneumonectomized mice stimulated DNA
      synthesis in lung epithelial cells. These results strongly suggest that HGF has a
      role as a pulmotrophic factor in postpneumonectomy compensatory lung
      regeneration.

PMID- 11970904
TI  - Regulation of telomerase activity in rat lung fibroblasts.
AB  - Fibroblasts from bleomycin-injured lungs express telomerase activity transiently
      during the period of active fibrosis, but the signal(s) responsible for its
      induction is (are) unknown. The objective of this study was to identify potential
      mediators capable of regulating telomerase activity induction in rat lung
      fibroblasts during pulmonary fibrosis. Lung fibroblasts from control (NRF) and
      bleomycin-treated (BRF) rats were isolated and treated in vitro with either basic
      fibroblast growth factor (bFGF) or interleukin-4 (IL-4). At selected time points
      after treatment, the cells were analyzed for telomerase activity, as well as
      telomerase reverse transcriptase (TERT) mRNA and protein by reverse
      transcriptase/polymerase chain reaction and Western blot, respectively. The
      results showed that bFGF could induce telomerase activity in NRF and stimulate
      further the induced activity in BRF. The bFGF effect was accompanied by increased
      TERT protein expression and a rapid but transient increase in TERT mRNA. In
      contrast, IL-4 inhibited the induced telomerase activity in BRF, which was
      accompanied by increased alpha-smooth muscle actin expression, an indicator of
      myofibroblast differentiation. These findings suggest that telomerase expression
      could be induced in rat lung fibroblasts by bFGF, but suppressed by IL-4, which
      promoted myofibroblast differentiation. The latter is consistent with the
      preferential expression of telomerase activity in fibroblasts relative to
      myofibroblasts.

PMID- 11970905
TI  - Expression profiling of the developing mouse lung: insights into the
      establishment of the extracellular matrix.
AB  - We have undertaken a comprehensive gene expression profiling of the entire
      process of murine lung development using oligonucleotide-based microarrays. Our
      data reveals the expression pattern of approximately 11,000 genes throughout the
      morphologic stages of lung development. This includes known genes with
      unappreciated pulmonary expression and novel genes with undefined functions.
      Traditional gene expression analysis techniques verify a high degree of
      confidence in the microarray data. Examination of the data confirms previously
      known patterns of expression for extracellular matrix genes and provides new
      information regarding relationships in temporal expression among groups of these
      genes. Large-scale cluster analysis reveals associations in the expression
      profile of specific genes with defined developmental processes. For instance, we
      identify groups of genes, which are coordinately expressed with extracellular
      matrix genes during lung development. These data should serve as a resource for
      the pulmonary research community and assist in deciphering the molecular
      mechanisms governing normal lung development as well as those involved in
      aberrant developmental pathology.

PMID- 11970906
TI  - Gene expression in bronchoalveolar lavage cells from scleroderma patients.
AB  - The hypothesis of this study is that activation of cell-mediated immunity with
      associated macrophage activation occurs in the lungs of scleroderma patients with
      lung inflammation. Gene expression profiles were determined in bronchoalveolar
      lavage (BAL) cells from scleroderma patients with and without lung inflammation
      and control subjects, using DNA array technology. Enzyme-linked immunosorbent
      assay was used to measure proteins in BAL fluids. Gene expression profiles were
      similar in BAL cells from patients without lung inflammation and control
      subjects. Gene expression profiles in patients with lung inflammation showed
      increased expression of chemokines and chemokine receptor genes, which would lead
      to migration of T cells, especially type 2 T cells, and phagocytic cells. Protein
      levels of pulmonary and activated-response chemokine and monocyte chemoattractant
      protein-1 were elevated. Other changes in gene expression suggested alterations
      in gene transcription, cell cycle control, vesicle transport, antigen-presenting
      function, and intracellular signaling. Two anti-inflammatory cytokines,
      interleukin-1 receptor antagonist and transforming growth factor-beta1, had
      increased expression, consistent with other human fibrotic lung diseases and
      animal models of lung fibrosis. These findings suggest recruitment of T cells and
      chronic macrophage activation in scleroderma patients at greater risk for lung
      fibrosis, but differ from typical delayed-type hypersensitivity responses,
      without prominence of type 1 T cells and inflammatory cytokines.

PMID- 11970907
TI  - Selective p38 activation in human non-small cell lung cancer.
AB  - The mitogen-activated protein kinase (MAPK) pathways transmit signals from the
      cell membrane to the nucleus. Activation of MAPK cascades may play a role in
      malignant transformation. We hypothesized that enhanced expression of one or more
      of these pathways would occur in human lung cancers. Using Western blot analysis
      of tissue homogenates from resected non- small cell lung cancers and matched non
      neoplastic lung tissue, we determined that only activated p38 was consistently
      increased in tumor compared with normal tissue. In vitro kinase assays confirmed
      that the levels of activated MAPK correlated with the activity of the enzymes,
      and immunohistochemical analysis confirmed the cellular localization of the
      activated MAPKs. We incubated a lung cancer cell line in a hypoxic chamber to
      simulate the hypoxic environment in solid lung tumors, but found no increase in
      p38 activation. Contrary to our expectations, ERK and JNK, the MAPK pathways
      traditionally associated with cell growth and perhaps malignant transformation,
      were not consistently activated in the human lung tumor samples. However, p38, a
      MAPK usually associated with stress responses, growth arrest, and apoptosis, was
      activated in all of the human lung cancer samples, suggesting an additional role
      for this pathway in malignant cell growth or transformation.

PMID- 11970908
TI  - Critical role of mitochondria, but not caspases, during glucocorticosteroid
      induced human eosinophil apoptosis.
AB  - Glucocorticosteroids are potent anti-inflammatory drugs used in the treatment of
      eosinophilic disorders. These molecules directly promote eosinophil apoptosis,
      yet the molecular mechanisms regulating this process remain ill-defined. We show
      here that stimulation of human peripheral blood eosinophils with dexamethasone
      induced DNA fragmentation, chromatin and cytoplasm condensation, and caspase-3
      activation, as assessed by the proteolysis of its zymogen form and by the
      increase of caspase-3-like activity in eosinophil lysates. These phenomena were
      accompanied by a reduced uptake of the mitochondrial potential-sensitive marker
      DiOC(6)(3), suggestive of mitochondrial membrane permeabilization. Eosinophil
      incubation with the caspase-3 inhibitor, Z-Asp-Glu-Val-Asp-fluromethylketone, or
      with the broad spectrum caspase inhibitor, Z-Val-Ala-Asp-fluromethylketone,
      inhibited caspase-3-like activity generation but failed to modify dexamethasone
      mediated loss in mitochondrial transmembrane potential and eosinophil apoptosis.
      In contrast, bongkrekic acid, a ligand of the mitochondrial permeability
      transition pore component, adenine nucleotide translocator, prevented both
      dexamethasone-induced mitochondrial disruption and apoptosis. We conclude that
      the mitochondrial permeability transition pore, rather than the caspase cascade,
      plays a critical role in the propagation of glucocorticosteroid-mediated
      apoptotic signals in human eosinophils.

PMID- 11970909
TI  - Macrophages are necessary for maximal nuclear factor-kappa B activation in
      response to endotoxin.
AB  - To define the role of macrophages in regulating the lung's response to
      Escherichia coli endotoxin (lipopolysaccharide [LPS]), depletion of macrophages
      was accomplished by administration of dichloromethylene diphosphonate
      (clodronate) delivered via intratracheal (i.t.) and/or intravenous (i.v.) routes.
      Clodronate reduced the number of macrophages in lung lavage 48 h after either
      i.t. or i.v. administration, but combined i.t. + i.v. clodronate achieved the
      most profound depletion (90%). Although i.t. clodronate alone had little effect
      on the evolution of lung inflammation, combined i.t. + i.v. clodronate treatment
      decreased neutrophilic alveolitis 4 h after exposure to aerosolized LPS by 80%
      compared with mice treated with empty liposomes. This decrease was associated
      with impaired activation of nuclear factor (NF)-kappa B and lower concentrations
      of tumor necrosis factor (TNF)-alpha in lung lavage fluid. Combined i.t. + i.v.
      clodronate markedly reduced lung NF-kappa B activation and the intensity of
      neutrophilic alveolitis after intraperitoneal (i.p.) LPS; however, i.v.
      clodronate alone had no effect on NF-kappa B activation in either liver or lung
      tissue or the development of neutrophilic alveolitis. We conclude that
      generalized macrophage depletion reduces NF-kappa B activation, generation of
      cytokines, and neutrophilic lung inflammation in response to gram negative
      bacterial endotoxin. These findings define the role of the macrophage as a
      critical component for initiation of the NF-kappa B-dependent innate immune
      response.

PMID- 11970910
TI  - Characterization of lung hyperresponsiveness, inflammation, and alveolar
      macrophage mediator production in allergy resistant and susceptible rats.
AB  - To better understand asthma pathogenesis, we characterized airway responsiveness,
      lung inflammation, and mediator production of alveolar macrophages (AM) after
      allergen sensitization and challenge in two strains of rats showing different
      susceptibilities in developing airway allergic reactions. Airway responsiveness
      to acethylcholine was measured 24 h after ovalbumin (OVA) challenge, whereas
      bronchoalveolar lavages were performed 5 min, 8 h, and 24 h after challenge.
      Brown Norway rats showed airway hyperresponsiveness after challenge, whereas lung
      resistance remained unchanged in Sprague-Dawley rats. Interestingly, Sprague
      Dawley rats developed a neutrophilic inflammation, whereas both neutrophils and
      eosinophils were increased in Brown Norway rats. AM mediator production varied
      with time with a lower tumor necrosis factor (TNF) and interleukin (IL)-10
      release at 8 h after challenge. OVA challenge stimulated spontaneous TNF and IL
      10 release by AM isolated 24 h after challenge in both strains of rats, although
      AM from Brown Norway rats released significantly more IL-10 and TNF. Furthermore,
      nitric oxide production was increased only in OVA-challenged (24 h) Brown Norway
      rats. Our results suggest that AM may participate to the expansion of Th2
      inflammation in Brown Norway rats and that differences in AM mediator production
      may explain, in part, distinct allergic susceptibilities in these two strains of
      rats.

PMID- 11970911
TI  - Production of interleukin-6 by skeletal myotubes: role of reactive oxygen
      species.
AB  - In the present study we have tested the ability of reactive oxygen species (ROS)
      to stimulate the production of interleukin (IL)- 6 from skeletal myocytes.
      Differentiated C2C12 murine skeletal muscle cells (myotubes) exposed to
      pyrogallol (PYR), xanthine/ xanthine-oxidase (X/XO), or H(2)O(2) for 24 h
      exhibited a concentration-dependent increase in IL-6 production. Unlike myotubes,
      incubation of myoblasts and endothelial cells with X/XO or PYR did not result in
      increased IL-6 release. In myotubes, superoxide dismutase and catalase blocked
      the ROS-induced IL-6 release. Exposure of myotubes to H(2)O(2) increased steady
      state IL-6 mRNA levels, and pretreatment of myotubes with actinomycin D or
      cycloheximide abolished the ROS-induced IL-6 production. In addition,
      pretreatment of cells with N-acetyl-cysteine blocked tumor necrosis factor (TNF)
      alpha-induced IL-6 release, suggesting that endogenously produced ROS participate
      in IL-6 production. Myotubes stimulated with H(2)O(2) exhibited increased I kappa
      B-alpha phosphorylation and degradation, and treatment of C2C12 with ROS
      generating agents increased activator protein (AP)-1 and nuclear factor (NF)
      kappa B-dependent promoter activity. Finally, preincubation of myotubes with the
      pharmacologic inhibitor of NF-kappa B, diethyldithiocarbamate, or transient
      transfection with an I kappa B-alpha mutant, inhibited the ROS-stimulated IL-6
      release. In conclusion, ROS stimulate IL-6 production from skeletal myotubes in a
      manner that involves transcriptional activation of the IL-6 gene through an NF
      kappa B-dependent pathway.

PMID- 11970912
TI  - Interferon-gamma enhances rhinovirus-induced RANTES secretion by airway
      epithelial cells.
AB  - Respiratory viruses, including rhinoviruses, infect respiratory epithelium and
      induce a variety of cytokines and chemokines that can initiate an inflammatory
      response. Cytokines, such as interferon (IFN)-gamma and tumor necrosis factor
      (TNF)-alpha, could enhance epithelial cell activation by inducing virus
      receptors. To test this hypothesis, effects of IFN-gamma or TNF-alpha on
      expression of intercellular adhesion molecule (ICAM)-1, rhinovirus binding, and
      virus-induced chemokine secretion on A549 and human bronchial epithelial cells
      (HBEC) were determined. The results varied with the type of cell. IFN-gamma was a
      stronger inducer of ICAM-1 and viral binding on HBEC, whereas TNF-alpha had
      greater effects on A549 cells. In addition, IFN-gamma, but not TNF-alpha,
      synergistically enhanced regulated on activation, normal T cells expressed and
      secreted (RANTES) mRNA expression and protein secretion induced by RV16 or RV49.
      To determine whether IFN-gamma could enhance RANTES secretion independent of
      effects on ICAM-1 and RV binding, HBEC were transfected with RV16 RNA in the
      presence or absence of IFN-gamma. RV16 RNA alone stimulated RANTES secretion, and
      this effect was enhanced by IFN-gamma. These results demonstrate that IFN-gamma
      can enhance rhinovirus-induced RANTES secretion by increasing viral binding, and
      through a second receptor-independent pathway. These findings suggest that IFN
      gamma, by upregulating RANTES secretion, could be an important regulator of the
      initial immune response to rhinovirus infections.

PMID- 11970913
TI  - Release and activity of matrix metalloproteinase-9 and tissue inhibitor of
      metalloproteinase-1 by alveolar macrophages from patients with chronic
      obstructive pulmonary disease.
AB  - Destruction of lung elastin is critical for development of emphysema associated
      with chronic obstructive pulmonary disease (COPD). Lung macrophages release
      elastolytic enzymes, including matrix metalloproteinase (MMP)-9, along with
      tissue inhibitors of MMP (TIMP). We examined the production and activity of
      macrophage-derived MMP-9 and TIMP-1 from alveolar macrophages (AM) from smokers
      with COPD, healthy smokers (HS), and nonsmokers (NS). AM were stimulated with
      either lipopolysaccharide (LPS), interleukin (IL)-1 beta, or cigarette smoke
      conditioned culture medium (CSM). AM from patients with COPD released greater
      amounts of MMP-9 with greater enzymatic activity than HS and NS. In contrast, AM
      from NS released more TIMP-1 than cells from HS and subjects with COPD. LPS and
      IL-1 beta caused a dose-dependent increase in MMP-9 release and activity,
      together with increased levels of TIMP-1. Dexamethasone prevented the increase in
      MMP-9 release, and increased TIMP-1 release. CSM increased MMP-9 and TIMP-1
      release from AM of all groups. Dexamethasone decreased CSM-stimulated MMP-9
      release, but had no effect on MMP-9 activity This study suggests that macrophages
      might be important in the development of COPD because these cells exhibit
      increased levels of elastolytic activity.

PMID- 11970914
TI  - Estrogen acutely activates prostacyclin synthesis in ovine fetal pulmonary artery
      endothelium.
AB  - Prostacyclin (PGI(2)) is a key mediator of pulmonary vasodilation during
      perinatal cardiopulmonary transition, at a time when fetal plasma estrogen levels
      are rising. We have previously shown that estradiol-17beta (E(2)) rapidly
      stimulates nitric oxide production by ovine fetal pulmonary artery endothelial
      cells (PAEC), and that this occurs through nongenomic mechanisms which are
      calcium- and tyrosine kinase-mitogen-activated protein (MAP) kinase-dependent. In
      the present study, we determined if E(2) acutely activates PGI(2) production in
      PAEC. E(2) (10(-8) M for 15 min) caused a 52% increase in PGI(2), the threshold
      concentration was 10(-10) M E(2), the effect occurred within 5 min, and it was
      not related to changes in cyclooxygenase type 1 (COX-1) or COX-2 abundance.
      Estrogen receptor (ER) alpha and ER beta proteins and mRNAs were found to be
      constitutively expressed in PAEC, and PGI(2) stimulation with E(2) was fully
      blocked by both ER antagonism with ICI 182,780, which is not selective for either
      ER isoform, and the ER beta-specific antagonist RR-tetrahydrochrysene. The rapid
      response to E(2) was also inhibited by calcium chelation, whereas genistein- or
      PD98059-induced inhibition of tyrosine kinase and MAP kinase kinase,
      respectively, had no effect. Thus, E(2) causes rapid stimulation of PGI(2)
      synthesis in fetal PAEC, this process is mediated by ER beta, and it is calcium
      dependent and tyrosine kinase-MAP kinase-independent. These mechanisms may play a
      role in pulmonary vasodilation in the perinatal period.

PMID- 11970915
TI  - Early mitochondrial dysfunction, superoxide anion production, and DNA degradation
      are associated with non-apoptotic death of human airway epithelial cells induced
      by Pseudomonas aeruginosa exotoxin A.
AB  - It has been shown that bacterial exoproducts may induce airway epithelium injury.
      During the epithelial repair process, the respiratory epithelial cells no more
      establish tight junctional intercellular complexes and may be particularly
      susceptible to bacterial virulence factors. In this study, we analyzed the effect
      of Pseudomonas aeruginosa exotoxin A (ETA) at different periods of time and
      concentrations on 16 HBE 14o(-) human bronchial epithelial cells in culture
      conditions inducing a phenotype of repairing cells. ETA treatment for 24 and 48 h
      led to the killing of 40.0 +/- 5.7% and 79.0 +/- 1.4% of the cells, respectively,
      as determined by the dimethylthiazole 2,5 diphenyl tetrazolium bromide assay. At
      1,000 ng/ml, ETA led to the killing of 25.2 +/- 6.6, 59.4 +/- 5.9, and 82.3 +/-
      3.7% of the cells, after treatment periods of 7, 24, and 48 h, respectively. Cell
      death could not be inhibited by z-VAD-fmk, a broad spectrum caspase inhibitor. By
      transmission electron microscopy, ultrastructural characteristics described in
      apoptosis were not detected in ETA-treated cells. Instead, the mitochondria of
      cells treated for 24 and 48 h with ETA at 100 and 1,000 ng/ml were highly
      condensed. Human nasal polyp epithelial cells in primary culture exposed to ETA
      at 1,000 ng/ml did not exhibit characteristic features of apoptotic cells either.
      Cytofluorometric analysis of ETA-treated 16 HBE 14o(-) cells labeled with
      DiOC(6)(3) and hydroethidine showed a time- and dose-dependent reduction of the
      mitochondrial transmembrane potential, detected 7 h after ETA treatment, and an
      increase in superoxide production, detected at 24 h, respectively. By a
      photometric assay, DNA degradation was also detected 7 h after cell treatment
      with ETA at 100 and 1,000 ng/ml. Taken together, our results show that ETA
      induced death of epithelial respiratory cells was preceded by early mitochondrial
      dysfunction and superoxide anion production, but was not followed by the
      classically described apoptotic pathways.

PMID- 11970916
TI  - Regulation of thioredoxin gene expression by vitamin A in human airway epithelial
      cells.
AB  - Human thioredoxin (Trx) is a 12-kD protein known to be involved in various
      reduction/oxidation reactions essential for cell growth and cellular injury
      repair. We previously demonstrated, based on nuclear run-on assay, that retinoic
      acid (RA) stimulated Trx gene expression in airway epithelial cells at the
      transcriptional level. Nucleotide sequencing of the 5'-flanking region of the
      human Trx gene revealed the presence of a TATA box at -28 and four RA response
      element (RARE)-like half sites at -426, -453, -507, and -626 nt. Transient
      transfection assays with a Trx promoter-reporter gene, chloramphenicol
      acetyltransferase (CAT), demonstrated a dose-dependent involvement of these four
      RARE-like half sites in RA-enhanced promoter activity. When the DNA fragment that
      flanks these four RARE-like half sites from -357 to -671 nt was introduced into a
      heterologous promoter of the tk-CAT2 vector, both basal and RA-stimulated CAT
      activities were observed. A site-directed mutagenesis approach demonstrated an
      essential role for RARE-I and RARE-II at -426 and -453 nt, respectively, and an
      auxiliary role for RARE-III at -507 nt in both basal and RA-stimulated CAT
      activities. Both in vivo and in vitro genomic footprinting experiments further
      demonstrated specific protein-DNA interactions in these "putative" RARE-I/II/III
      half sites. Gel electrophoretic mobility shift assays demonstrated specific
      interactions of these RARE-like half sites with the nuclear extracts obtained
      from RA-treated cultures. The anti-RAR-alpha antibody super-shift experiment
      further confirmed the interactions of RARE-I/II sites with RAR-alpha nuclear
      receptor. These results suggest a classic RARE/RAR interaction involved in RA
      stimulated Trx gene expression in human airway epithelium.

PMID- 11970918
TI  - Precocious puberty: a parent's perspective.

PMID- 11970919
TI  - In sickness and in health: the importance of translational regulation.

PMID- 11970917
TI  - Paediatric mastocytosis.

PMID- 11970920
TI  - Coping and health service utilisation in a UK study of paediatric sickle cell
      pain.
AB  - AIMS: To assess sickle cell pain and coping in children and to examine the
      relation between these factors and the utilisation of health services. METHODS:
      Cross sectional study involving 67 children with sickle cell disease attending
      three London hospitals. Interviews and questionnaires involved measures of pain,
      health service utilisation, and coping responses (measured with the Coping
      Strategies Questionnaire (CSQ), revised for children with sickle cell disease).
      Medical data on complications, haemoglobin (Hb) levels, and foetal haemoglobin
      (HbF) percentage were also collected. RESULTS: Pain accounted for about 24% of
      hospital service use, independent of age, sex, number of with sickle cell disease
      complications, and Hb levels. However, 42% of patients had not utilised hospital
      services in the past 12 months. Three higher order factors emerged from analysis
      of the CSQ (active coping, affective coping, passive adherence coping). Pain
      severity was predicted by passive adherence coping, while utilisation of hospital
      services was predicted by active coping. CONCLUSIONS: Sickle cell disease in
      children involves severe recurrent pain leading to hospitalisation in some cases.
      Psychological coping patterns are relevant to both pain experience, and the use
      of acute hospital services. It is likely that children would benefit from
      community based interventions that incorporate both medical and psychological
      assessments.

PMID- 11970921
TI  - A scoring system for bruise patterns: a tool for identifying abuse.
AB  - AIMS: To determine whether abused and non-abused children differ in the extent
      and pattern of bruising, and whether any differences which exist are sufficiently
      great to develop a score to assist in the diagnosis of abuse. METHODS: Total
      length of bruising in 12 areas of the body was determined in 133 physically
      abused and 189 control children aged 1-14 years. RESULTS: Our method of recording
      bruises by site, maximum dimension, and shape was easy to use. There were clear
      differences between cases and controls in the total length of bruises. These
      differences were at their greatest in the head and neck and were less notable in
      the limbs. A scoring system was developed using logistic regression analysis
      using total lengths of bruising in five regions of the body. Good discrimination
      between the two sets of children was achieved using this score; by including a
      variable that indicates whether a bruise had a recognisable shape the
      discrimination could be made even better. Given a prior probability of abuse the
      score can be used to give posterior odds of abuse, given a particular bruising
      pattern. CONCLUSIONS: The scoring system provides a measure that discriminates
      between abused and non-abused children, which should be straightforward to
      implement, though the results must be interpreted carefully. We do not see this
      score as replacing the complex qualitative analysis of the diagnosis of abuse.
      This clearly includes history as well as examination, but rather as the beginning
      of the development of an important aid in this process.

PMID- 11970924
TI  - Deaths from pertussis are underestimated in England.
AB  - AIMS: To improve estimates of deaths from pertussis in England and to identify
      reasons for under ascertainment. METHODS: Comparison of deaths identified from
      enhanced laboratory pertussis surveillance, hospital episode statistics (HES),
      and Office for National Statistics (ONS) death registrations in England, 1994 to
      1999. RESULTS: A total of 33 deaths were identified, 88% of infants less than 4
      months old. There was overlap between all sources; 22 deaths were identified in
      the enhanced pertussis surveillance system, 18 in ONS mortality data, and nine in
      HES. Children who had died from pertussis without mention of pertussis on the
      death certificate were more likely to have been certified by coroners than those
      with mention of pertussis (p = 0.0005). Using capture-recapture analysis, the
      total number of deaths from pertussis in the five and a half year period is
      estimated to be 46 (95% CI 37 to 71), or around nine deaths per year.
      CONCLUSIONS: National mortality statistics significantly under estimate deaths
      from pertussis in England and are inadequate for monitoring the national
      immunisation programme. The largest number of deaths is identified through
      enhanced laboratory surveillance. Death registration systems should take into
      account available microbiological information to ensure that cause of death is
      accurately assigned.

PMID- 11970923
TI  - Convulsions and retinal haemorrhage: should we look further?
AB  - BACKGROUND AND AIMS: The prevalence of retinal haemorrhages after convulsions is
      not well established. As these haemorrhages are considered characteristic of
      child abuse, we investigated their occurrence after convulsive episodes to see
      whether the finding of haemorrhage should prompt further investigation. METHODS:
      Prospective study of 153 children (aged 2 months to 2 years), seen in the
      emergency department after a convulsive episode. After a thorough history and
      physical examination, a retinal examination was performed by an ophthalmologist.
      If findings were positive, further investigation was undertaken to rule out
      systemic disorder or child abuse. RESULTS: One child was found with unilateral
      retinal haemorrhages following an episode of a simple febrile convulsion. A
      thorough investigation uncovered no other reason for this finding. CONCLUSION:
      Retinal haemorrhages following a convulsive episode are rare. Such a finding
      should trigger an extensive search for other reasons, including child abuse.

PMID- 11970926
TI  - Unilateral exophthalmos in a 2(1/2) year old girl.

PMID- 11970925
TI  - Hepatitis C-Z: recent advances.
AB  - In this review, recently identified hepatitis viruses (hepatitis C, hepatitis D,
      hepatitis E, hepatitis F, hepatitis G, transfusion transmissible virus) are
      described, and the implications for paediatric liver disease discussed.

PMID- 11970927
TI  - Liver disease in transfusion dependent thalassaemia major.
AB  - AIMS: To study the prevalence and severity of liver diseases of transfusion
      dependent thalassaemia major patients, and correlate the histological and
      biochemical changes of iron overload in liver with the peripheral blood markers.
      METHOD: Liver biopsy was performed to assess the histological changes and liver
      iron content (LIC). RESULTS: One hundred patients were evaluated (median age 11.7
      years, range 1.5-27). A total of 81 liver biopsies were performed in 73 patients;
      43 samples were analysed for LIC. Grade 3-4 haemosiderosis and hepatic fibrosis
      was found in 44% and 30% of patients respectively; both were significantly
      associated with higher serum ferritin, liver enzymes, and LIC. Very high LIC (>15
      mg/g dry weight) was present in 16.3% of patients. CONCLUSION: Severe
      haemosiderosis and hepatic fibrosis were common in patients with thalassaemia
      major despite the use of chelation therapy. Liver biopsy provided information on
      fibrosis and LIC which could not be accurately predicted from peripheral blood
      markers.

PMID- 11970929
TI  - Hirschsprung's disease: functional and psychological follow up comparing total
      colonic and rectosigmoid aganglionosis.
AB  - AIMS: To compare the long term functional and psychosocial outcomes following
      surgical treatment for total colonic aganglionosis (TCA) with those in an age and
      gender matched group of patients with rectosigmoid aganglionosis (RSA). METHODS:
      Fifteen patients with TCA matched for age and gender with 15 patients with RSA
      were studied 7-17 years after the definitive operation. The internal and external
      sphincters were examined using anal endosonography. Functional outcome (faecal
      continence) was assessed by a surgeon not involved in the patients' care, and by
      a research psychologist in separate assessment sessions. The behavioural and
      emotional status of the patients was also assessed. RESULTS: Based on the
      surgeon's assessment, 6/15 TCA and 7/15 RSA patients were continent. In
      comparison, based on the psychological interview, 2/15 TCA and 6/15 RSA patients
      were continent. The TCA patients reported significantly more
      behavioural/emotional problems and lower levels of self esteem than the RSA
      patients. The parent and teacher assessments of psychosocial status revealed no
      differences between the groups. There was no association between incontinence and
      psychosocial adjustment in either group. There was no association between the
      assessments of functional outcome and the endosonographic appearance of the anal
      sphincters. CONCLUSIONS: The proportion of patients with faecal incontinence 7-17
      years after definitive surgery was high in both groups, but no association was
      found between incontinence and the psychosocial outcome measures. TCA patients
      perceived themselves as less well adjusted than their matched pairs. Differences
      between the groups in length of hospitalisation and severity of illness,
      especially in infancy and early childhood, may account for these differences.

PMID- 11970930
TI  - Presentation and outcome of severe anticholinesterase insecticide poisoning.
AB  - AIMS: To document the patterns of presentation and outcome of severe
      anticholinesterase insecticide poisoning in children requiring intensive care.
      METHODS: Retrospective case note review of all 5541 children admitted to the
      paediatric intensive care unit (PICU) of a university hospital during the 10
      years from January 1990 to May 2000. Fifty four children (1%) with
      anticholinesterase insecticide poisoning were identified. Presenting features,
      route of exposure, treatment, complications, and mortality were recorded. Data
      were analysed by the Fisher's exact and Mann-Whitney tests. RESULTS: More
      children than expected were from a rural area (46% versus 25%). Decontamination
      occurred in 50% of children prior to PICU admission. Enteral exposure was most
      common (n = 27; 50%). Median pseudocholinesterase level was 185 IU/l (range 75
      7404). Median total dose of atropine required to maintain mydriasis was 0.3 mg/kg
      (range 0.03-16.7) over a median of 10 hours (range 1-160). Complications included
      coma (31%), seizures (30%), shock (9%), arrhythmias (9%), and respiratory failure
      requiring ventilation (35%). No significant differences were detected in
      incidence of seizures, cardiac arrhythmias, respiratory failure, mortality,
      duration of ventilation, or PICU stay, according to route of exposure, or state
      of decontamination. Four children died (7%). Mortality was associated with the
      presence of a cardiac arrhythmia (likelihood ratio 8.3) and respiratory failure
      (likelihood ratio 3.3). CONCLUSION: The mortality and morbidity of severe
      anticholinesterase insecticide poisoning in childhood is not related to route of
      exposure, or to delay in decontamination. However, the presence of either a
      cardiac arrhythmia or respiratory failure is associated with a poor prognosis.

PMID- 11970932
TI  - Amplifying the error.

PMID- 11970931
TI  - Beneficial effect of long term intravenous bisphosphonate treatment of
      osteogenesis imperfecta.
AB  - AIM: To find an effective symptomatic treatment for osteogenesis imperfecta (OI).
      METHODS: In a prospective observational study disodium pamidronate (APD) was
      given as monthly intravenous infusions to 28 children and adolescents (aged 0.6
      18 years) with severe OI or a milder form of the disease, but with spinal
      compression fractures. RESULTS: During treatment for 2-9 years, dual energy x ray
      absorptiometry measurements of the total body and of the lumbar spine showed a
      gradual increase in bone density. All bone metabolism variables in serum
      (alkaline phosphatase, osteocalcin, procollagen 1 C-terminal peptide, collagen 1
      teleopeptide) and urine (deoxypyridinoline) indicated that there was a decrease
      in bone turnover. All patients experienced beneficial effects and the younger
      patients reported a major improvement in wellbeing, pain, and mobility without
      significant side effects. Vertebral remodelling was also seen. CONCLUSIONS: APD
      seems to be an efficient symptomatic treatment for children and adolescents with
      OI.

PMID- 11970933
TI  - The effect of brief neonatal exposure to cows' milk on atopic symptoms up to age
      5.
AB  - AIMS: To determine the effect of brief early exposure to cows' milk on the
      expression of atopy during the first five years of life. METHODS: Follow up
      analysis of a double blind, placebo controlled, randomised feeding intervention
      trial (BOKAAL study). Subjects were 1108 children from 1533 initially randomised
      breast fed neonates in the Netherlands. Atopic disease and prevalence of allergic
      symptoms at age 1, 2, and 5, and specific IgE at age 1 and 5 were determined.
      RESULTS: Atopic disease in the first year was found in 10.0% (cows' milk) versus
      9.3% (placebo) of the children, with a relative risk (RR) of 1.07. No differences
      were found in the second year either. At age 5, atopic disease was found in 26.3%
      (cows' milk) versus 25.0% (placebo), RR 1.05. There was no difference in the
      prevalence of allergic symptoms. Specific IgE to cows' milk (RAST positive 2+ or
      more) was 5.8% (cows' milk) versus 4.1% (placebo) at age 1 (RR 1.43), and 5.3%
      versus 3.0% at age 5 (RR 1.77). There was no difference in sensitisation to other
      common allergens between the two groups. CONCLUSION: Early, brief exposure to
      cows' milk in breast fed children is not associated with atopic disease or
      allergic symptoms up to age 5.

PMID- 11970935
TI  - Bronchiolitis hospitalisations in the Netherlands from 1991 to 1999.
AB  - In order to analyse trends in the bronchiolitis hospitalisations in the
      Netherlands from 1991 to 1999 for children aged 0-4 years, the national number of
      bronchiolitis hospitalisations were compared with those of asthma and pneumonia
      hospitalisations of the same age group. The number of bronchiolitis
      hospitalisations significantly increased, whereas the number of asthma and
      pneumonia hospitalisations remained unchanged.

PMID- 11970936
TI  - Rapid painless diagnosis of viral respiratory infection.
AB  - The concordance of nasal compared with nasopharyngeal swabs was assessed for the
      diagnosis of respiratory viral infections, and the degree of discomfort
      associated with each procedure was compared. The use of nasal swabs was shown to
      be as accurate but significantly less painful than nasopharyngeal swabs for virus
      diagnosis.

PMID- 11970937
TI  - Tailoring treatment for retinoblastoma.

PMID- 11970938
TI  - Randomised trial of the effects of structuring clinic correspondence.
AB  - We performed a randomised controlled crossover trial of clinic letters.
      Structured letters were compared with conventional letters containing problem
      lists. There were 32 participants; 25 preferred the structured letter. Median
      rating and items identified were higher for the structured letter. Structured
      clinical correspondence with paragraph headings is strongly preferred and
      increases comprehension.

PMID- 11970939
TI  - Antioxidant enzymes in blood of patients with Friedreich's ataxia.
AB  - BACKGROUND AND AIMS: Increased generation of reactive oxygen species and
      mitochondrial dysfunction may underlie the pathophysiology of Friedreich's
      ataxia, the most common inherited ataxia, due to GAA expansion in a gene coding
      for a mitochondrial protein (frataxin), implicated in the regulation of iron
      metabolism. Because iron overload would cause oxidative stress in Friedreich's
      ataxia, we investigated the enzyme antioxidant system in the blood of 14 patients
      by determining superoxide dismutase, glutathione peroxidase, and glutathione
      transferase catalytic activities. We also studied the glutathione S-transferase
      genotype polymorphism in order to evaluate its possible influence on enzyme
      activity. METHODS: Blood samples were obtained from 14 unrelated patients with
      Friedreich's ataxia and 21 age matched healthy subjects. Antioxidant enzyme
      determinations were spectrophotometrically assayed using specific substrates; the
      glutathione S-transferase genotype polymorphism was analysed by endonuclease
      restriction mapping of exon 5 and 6 amplification products. RESULTS: There was a
      significant elevation of the superoxide dismutase/glutathione peroxidase activity
      ratio (0.037 (0.01) v 0.025 (0.008) of controls) and an 83% rise of glutathione
      transferase specific activity (0.22 (0.1) v 0.12 (0.03) nmol/min/mg protein) in
      blood of patients with Friedreich's ataxia than in the controls. The genotype
      polymorphism of glutathione S-transferase enzyme did not show any relevant
      differences when compared to that of healthy subjects. CONCLUSIONS: Data show an
      impairment in vivo of antioxidant enzymes in patients with Friedreich's ataxia
      and provide evidence of an increased sensitivity to oxidative stress, supporting
      a consistent role of free radical cytotoxicity in the pathophysiology of the
      disease.

PMID- 11970940
TI  - A touch of the 'flu.

PMID- 11970942
TI  - Towards evidence based medicine for paediatricians.

PMID- 11970941
TI  - Does giving albumin infusion in hypoalbuminaeimic children with oncological
      disease affect colloid osmotic pressure and outcome?

PMID- 11970943
TI  - Does magnesium sulphate have a role in the management of paediatric status
      asthmaticus?

PMID- 11970944
TI  - Is chiropractic an effective treatment in infantile colic?

PMID- 11970945
TI  - Fame, power, and Asperger's syndrome.

PMID- 11970946
TI  - Coping with sickle cell disease: a self help manual.

PMID- 11970947
TI  - Characterization of the nuclear import and export functions of Ikappa B(epsilon).
AB  - Control over the nuclear localization of nuclear factor kappaB/Rel proteins is
      accomplished in large part through association with members of the inhibitor of
      kappaB (IkappaB) protein family. For example, the well studied IkappaBalpha
      protein actively shuttles between the nucleus and the cytoplasm and both inhibits
      nuclear import and mediates nuclear export of NF-kappaB/Rel proteins. In
      contrast, the IkappaBbeta protein can inhibit nuclear import of NF-kappaB/Rel
      proteins but does not remove NF-kappaB/Rel proteins from the nucleus. To further
      understand how the IkappaB proteins control the nuclear-cytoplasmic distribution
      of NF-kappaB/Rel proteins, we have characterized the nuclear import and nuclear
      export functions of IkappaBepsilon. Our results indicate that the IkappaBepsilon
      protein, like the IkappaBalpha protein, actively shuttles between the nucleus and
      the cytoplasm. Similar to IkappaBalpha, nuclear import of IkappaBepsilon is
      mediated by its ankyrin repeat domain and is not blocked by the dominant-negative
      RanQ69L protein. However, the nuclear import function of the IkappaBepsilon
      ankyrin repeat domain is markedly less efficient than that of IkappaBalpha, with
      the result that nuclear shuttling of IkappaBepsilon between the nucleus and the
      cytoplasm is significantly slower than IkappaBalpha. Nuclear export of
      IkappaBepsilon is mediated by a short leucine-rich nuclear export sequence (NES)
      like sequence ((343)VLLPFDDLKI(352)), located between amino acids 343 and 352.
      This NES-like sequence is required for RanGTP-dependent binding of IkappaBepsilon
      to CRM1. Nuclear accumulation of IkappaB(epsilon) is increased by either
      leptomycin B treatment or alanine substitutions within the IkappaBepsilon-derived
      NES. A functional NES is required for both efficient cytoplasmic retention and
      post-induction control of c-Rel by IkappaBepsilon, consistent with the notion
      that IkappaBepsilon-mediated nuclear export contributes to control over the
      nucleocytoplasmic distribution of NF-kappaB/Rel proteins.

PMID- 11970948
TI  - The x-ray crystal structure of the NF-kappa B p50.p65 heterodimer bound to the
      interferon beta -kappa B site.
AB  - We have determined the x-ray crystal structure of the transcription factor NF
      kappaB p50.p65 heterodimer complexed to kappaB DNA from the cytokine interferon
      beta enhancer (IFNbeta-kappaB). To better understand how the binding modes of NF
      kappaB on its two best studied DNA targets might contribute to promoter-specific
      transcription, this structure is compared with the previously determined complex
      crystal structure containing NF-kappaB bound to the Ig kappa light chain gene
      enhancer as well as to a second NF-kappaB.Ig kappa light chain gene enhancer
      complex also reported in this paper. The global binding modes of all NF
      kappaB.DNA complex structures are similar, although crystal-packing interactions
      lead to differences between identical complexes of the same crystallographic
      asymmetric unit. An extensive network of stacked amino acid side chains that
      contribute to base-specific DNA contacts is conserved among the three complexes.
      Consistent with earlier reports, however, the IFNbeta-kappaB DNA is bent
      significantly less by NF-kappaB than is the Ig kappa light chain gene enhancer.
      This and other small structural changes may play a role in explaining why NF
      kappaB-directed transcription is sensitive to the context of specific promoters.
      The precise molecular mechanism behind the involvement of the high mobility group
      protein I(Y) in interferon beta enhanceosome formation remains elusive.

PMID- 11970949
TI  - The kappa B DNA sequence from the HIV long terminal repeat functions as an
      allosteric regulator of HIV transcription.
AB  - NF-kappaB is an inducible transcription factor involved in the immune response,
      inflammation, and viral transcription. To address how the two NF-kappaB and three
      Sp1 binding sites of the human immunodeficiency virus (HIV) long terminal repeat
      (LTR) control multiple activator assembly and transcription, we first observed
      and compared unique conformations between the crystallographic structure of the
      NF-kappaB p50.p65 heterodimer bound to the uPA-kappaB target site to that of the
      p50.p65.HIV-kappaB complex. Next, cooperativity between two NF-kappaB molecules
      bound to tandem HIV-kappaB sequences was measured as well as that of NF-kappaB
      and transcription factor Sp1 when bound to adjacent sites. The cooperativity of
      hybrid HIV-LTR enhancers was measured with the 3' kappaB site converted to uPA
      kappaB or to interferon beta gene enhancer kappaB. The hybrids were defective in
      transcriptional activator assembly and less active transcriptionally. These
      functional differences correlate with observed conformational differences and
      demonstrate that distinct kappaB DNA sequences function as allosteric regulators
      in a gene-specific manner.

PMID- 11970950
TI  - Ets-1 positively regulates Fas ligand transcription via cooperative interactions
      with Sp1.
AB  - The FasL/Fas system has been implicated in smooth muscle cell apoptosis and
      atherosclerotic plaque instability, a process that can lead to plaque rupture,
      precipitating myocardial infarction and sudden death. The transcriptional
      mechanisms regulating FasL gene expression in vascular smooth muscle cells are
      poorly understood. We recently described a novel mechanism mediating inducible
      FasL gene expression in smooth muscle cells involving the zinc finger
      transcription factor Sp1 (Kavurma, M. M., Santiago, F. S., Bofocco, E., and
      Khachigian, L. M. (2001) J. Biol. Chem. 276, 4964-4971). We now show that FasL
      gene expression is governed by cooperative activation between Sp1 and the Ets
      family of transcription factors. The overexpression of Ets-1 was sufficient to
      induce FasL promoter-dependent expression and protein synthesis. Ets-1 activation
      of the promoter was abrogated either by deletion or mutation of the Sp1 binding
      site. The overexpression of Ets-1 together with Sp1 produced cooperative
      activation of the FasL promoter. Sp1 induction of the FasL promoter was abrogated
      by an Ets-1 mutant lacking the activation domain. Conversely, Ets-1 activation of
      the promoter was blocked by an Sp1 mutant bearing the DNA-binding domain. The
      mutation of the (-365)GGAA(-362) element in the FasL promoter abolished Ets-1
      activation and attenuated Sp1-inducible gene expression. Immunoprecipitation and
      supershift experiments revealed that endogenous Ets-1 and Sp1 physically interact
      and co-occupy this site. Thus, FasL gene expression in vascular smooth muscle
      cells is mediated by cooperativity between Ets-1 and Sp1.

PMID- 11970951
TI  - Protein film voltammetry reveals distinctive fingerprints of nitrite and
      hydroxylamine reduction by a cytochrome C nitrite reductase.
AB  - The cytochrome c nitrite reductases perform a key step in the biological nitrogen
      cycle by catalyzing the six-electron reduction of nitrite to ammonium. Graphite
      electrodes painted with Escherichia coli cytochrome c nitrite reductase and
      placed in solutions containing nitrite (pH 7) exhibit large catalytic reduction
      currents during cyclic voltammetry at potentials below 0 V. These catalytic
      currents were not observed in the absence of cytochrome c nitrite reductase and
      were shown to originate from an enzyme film engaged in direct electron exchange
      with the electrode. The catalytic current-potential profiles observed on
      progression from substrate-limited to enzyme-limited nitrite reduction revealed a
      fingerprint of catalytic behavior distinct from that observed during
      hydroxylamine reduction, the latter being an alternative substrate for the enzyme
      that is reduced to ammonium in a two electron process. Cytochrome c nitrite
      reductase clearly interacts differently with these two substrates. However,
      similar features underlie the development of the voltammetric response with
      increasing nitrite or hydroxylamine concentration. These features are consistent
      with coordinated two-electron reduction of the active site and suggest that the
      mechanisms for reduction of both substrates are underpinned by common rate
      defining processes.

PMID- 11970952
TI  - Crystal structure of NC1 domains. Structural basis for type IV collagen assembly
      in basement membranes.
AB  - Type IV collagen, which is present in all metazoan, exists as a family of six
      homologous alpha(IV) chains, alpha1-alpha6, in mammals. The six chains assemble
      into three different triple helical protomers and self-associate as three
      distinct networks. The network underlies all epithelia as a component of basement
      membranes, which play important roles in cell adhesion, growth, differentiation,
      tissue repair and molecular ultrafiltration. The specificity of both protomer and
      network assembly is governed by amino acid sequences of the C-terminal
      noncollagenous (NC1) domain of each chain. In this study, the structural basis
      for protomer and network assembly was investigated by determining the crystal
      structure of the ubiquitous [(alpha1)(2).alpha2](2) NC1 hexamer of bovine lens
      capsule basement membrane at 2.0 A resolution. The NC1 monomer folds into a novel
      tertiary structure. The (alpha1)(2).alpha2 trimer is organized through the unique
      three-dimensional domain swapping interactions. The differences in the primary
      sequences of the hypervariable region manifest in different secondary structures,
      which determine the chain specificity at the monomer-monomer interfaces. The
      trimer-trimer interface is stabilized by the extensive hydrophobic and
      hydrophilic interactions without a need for disulfide cross-linking.

PMID- 11970953
TI  - Activation of Rap1B by G(i) family members in platelets.
AB  - It has become increasingly appreciated that receptors coupled to G(alpha)(i)
      family members can stimulate platelet aggregation, but the mechanism for this has
      remained unclear. One possible mediator is the small GTPase, Rap1, which has been
      shown to contribute to integrin activation in several cell lines and to be
      activated by a calcium-dependent mechanism in platelets. Here, we demonstrate
      that Rap1 is also activated by G(alpha)(i) family members in platelets. First, we
      show that platelets from mice lacking the G(alpha)(i) family member G(alpha)(z)
      (which couples to the alpha(2A) adrenergic receptor) are deficient in epinephrine
      stimulated Rap1 activation. We also show that platelets from mice lacking
      G(alpha)(i2), which couples to the ADP receptor, P2Y12, exhibit reduced Rap1
      activation in response to ADP. In contrast, platelets from mice that lack
      G(alpha)(q) show no decrease in the ability to activate Rap1 in response to
      epinephrine but show a partial reduction in ADP-stimulated Rap1 activation. This
      result, combined with studies of human platelets treated with ADP receptor
      selective inhibitors, indicates that ADP-stimulated Rap1 activation in human
      platelets is dependent on both the G(alpha)(i)-coupled P2Y12 receptor and the
      G(alpha)(q)-coupled P2Y1 receptor. G(alpha)(i)-dependent activation of Rap1 in
      platelets does not appear to be mediated by enhanced intracellular calcium
      release because no increase in intracellular calcium concentration was detected
      in response to epinephrine and because the calcium response to ADP was not
      diminished in platelets from the G(alpha)(i2)-/- mouse. Finally, using human
      platelets treated with selective inhibitors of phosphatidylinositol 3-kinase
      (PI3K) and mouse platelets selectively lacking the G(beta)(gamma)-activated form
      of his enzyme (PI3Kgamma), we show that G(i)-mediated Rap1 activation is PI3K
      dependent. In summary, activation of Rap1 can be stimulated by G(alpha)(i)- and
      PI3K-dependent mechanisms in platelets and by G(q)- and Ca(2+)-dependent
      mechanisms, both of which may play a role in promoting platelet activation.

PMID- 11970954
TI  - Heme nitrosylation of deoxyhemoglobin by s-nitrosoglutathione requires copper.
AB  - NO reactions with hemoglobin (Hb) likely play a role in blood pressure
      regulation. For example, NO exchange between Hb and S-nitrosoglutathione (GSNO)
      has been reported in vitro. Here we examine the reaction between GSNO and deoxyHb
      (HbFe(II)) in the presence of both Cu(I) (2,9-dimethyl-1, 10-phenanthroline
      (neocuproine)) and Cu(II) (diethylenetriamine-N,N,N',N",N"-pentaacetic acid)
      chelators using a copper-depleted Hb solution. Spectroscopic analysis of deoxyHb
      (HbFe(II))/GSNO incubates shows prompt formation (<5 min) of approximately 100%
      heme-nitrosylated Hb (HbFe(II)NO) in the absence of chelators, 46% in the
      presence of diethylenetriamine-N,N,N',N",N"-pentaacetic acid, and 25% in the
      presence of neocuproine. Negligible (<2%) HbFe(II)NO was detected when
      neocuproine was added to copper-depleted HbFe(II)/GSNO incubates. Thus,
      HbFe(II)NO formation via a mechanism involving free NO generated by Cu(I)
      catalysis of GSNO breakdown is proposed. GSH is a source of reducing equivalents
      because extensive GSSG was detected in HbFe(II)/GSNO incubates in the absence of
      metal chelators. No S-nitrosation of HbFe(II) was detected under any conditions.
      In contrast, the NO released from GSNO is directed to Cysbeta(93) of oxyHb in the
      absence of chelators, but only metHb formation is observed in the presence of
      chelators. Our findings reveal that the reactions of GSNO and Hb are controlled
      by copper and that metal chelators do not fully inhibit NO release from GSNO in
      Hb-containing solutions.

PMID- 11970955
TI  - Inhibition of platelet adhesion and aggregation by a defined region (Gly-486-Lys
      502) of high molecular weight kininogen.
AB  - Proteolytic cleavage of single chain high molecular weight kininogen (HK) by
      kallikrein releases the short-lived vasodilator bradykinin and leaves behind two
      chain high molecular weight kininogen (HKa). HKa and particularly its His-Gly-Lys
      rich domain 5 have been previously reported to exert anti-adhesive properties by
      binding to the extracellular matrix protein vitronectin (VN). In this study the
      ability of HKa and domain 5 to interfere with platelet adhesion and aggregation
      was investigated. In a purified system HKa and particularly domain 5 but not HK
      inhibited the binding of VN to the alpha(IIb)beta(3) integrin, whereas the
      binding of fibrinogen to this integrin was not affected. The region Gly-486-Lys
      502 from the carboxyl terminus of the domain 5 was identified as responsible for
      inhibition of the VN-alpha(IIb)beta(3)-integrin interaction, as this portion was
      also found to mediate kininogen binding to VN. Through these interactions, HKa,
      the isolated domain 5, and the peptide Gly-486-Lys-502 abrogated the
      alpha(IIb)beta(3)-integrin-dependent adhesion of human platelets to VN but not to
      fibrinogen. The codistribution of VN and HKa at sites of ex vivo platelet
      aggregation was demonstrated by transmission immune electron microscopy,
      indicating that the described interaction is likely to take place in vivo.
      Moreover, domain 5 and the peptide Gly-486-Lys-502 dose-dependently blocked
      platelet aggregation, resembling the inhibitory effect of monoclonal antibody
      13H1 against multimeric VN. Finally, treatment of mice with isolated domain 5
      resulted in a significantly prolonged tail bleeding time. Taken together, our
      data emphasize the inhibitory role of HK domain 5 on platelet adhesion and
      aggregation; new anti-thrombotic compounds may become available on the basis of
      peptide Gly-486-Lys-502 of HK domain 5.

PMID- 11970956
TI  - Indolmycin resistance of Streptomyces coelicolor A3(2) by induced expression of
      one of its two tryptophanyl-tRNA synthetases.
AB  - Aminoacyl-tRNA synthetases, a family of enzymes essential for protein synthesis,
      are promising targets of antimicrobials. Indolmycin, a secondary metabolite of
      Streptomyces griseus and a selective inhibitor of prokaryotic tryptophanyl-tRNA
      synthetase (TrpRS), was used to explore the mechanism of inhibition and to
      explain the resistance of a naturally occurring strain. Streptomyces coelicolor
      A3(2), an indolmycin-resistant strain, contains two trpS genes encoding distinct
      TrpRS enzymes. We show that TrpRS1 is indolmycin-resistant in vitro and in vivo,
      whereas TrpRS2 is sensitive. The lysine (position 9) in the enzyme tryptophan
      binding site is essential for making TrpRS1 indolmycin-resistant. Replacement of
      lysine 9 by glutamine, which at this position is conserved in most bacterial
      TrpRS proteins, abolished the ability of the mutant trpS gene to confer
      indolmycin resistance in vivo. Molecular modeling suggests that lysine 9
      sterically hinders indolmycin binding to the enzyme. Tryptophan recognition
      (assessed by k(cat)/K(M)) by TrpRS1 is 4-fold lower than that of TrpRS2.
      Examination of the mRNA for the two enzymes revealed that only TrpRS2 mRNA is
      constitutively expressed, whereas mRNA for the indolmycin-resistant TrpRS1 enzyme
      is induced when the cells are exposed to indolmycin.

PMID- 11970957
TI  - Characterization of a direct oxygen sensor heme protein from Escherichia coli.
      Effects of the heme redox states and mutations at the heme-binding site on
      catalysis and structure.
AB  - A protein containing a heme-binding PAS (PAS is from the protein names in which
      imperfect repeat sequences were first recognized: PER, ARNT, and SIM) domain from
      Escherichia coli has been implied a direct oxygen sensor (Ec DOS) enzyme. In the
      present study, we isolated cDNA for the Ec DOS full-length protein, expressed it
      in E. coli, and examined its structure-function relationships for the first time.
      Ec DOS was found to be tetrameric and was obtained as a 6-coordinate low spin
      ferric heme complex. Its alpha-helix content was calculated as 53% by CD
      spectroscopy. The redox potential of the heme was found to be +67 mV versus SHE.
      Mutation of His-77 of the isolated PAS domain abolished heme binding, whereas
      mutation of His-83 did not, suggesting that His-77 is one of the heme axial
      ligands. Ferrous, but not ferric, Ec DOS had phosphodiesterase (PDE) activity of
      nearly 0.15 min(-1) with cAMP, which was optimal at pH 8.5 in the presence of
      Mg(2+) and was strongly inhibited by CO, NO, and etazolate, a selective cAMP PDE
      inhibitor. Absorption spectral changes indicated tight CO and NO bindings to the
      ferrous heme. Therefore, the present study unequivocally indicates for the first
      time that Ec DOS exhibits PDE activity with cAMP and that this is regulated by
      the heme redox state.

PMID- 11970958
TI  - The conserved helix C region in the superfamily of interferon-gamma /interleukin
      10-related cytokines corresponds to a high-affinity binding site for the HSP70
      chaperone DnaK.
AB  - HSP70 chaperones mediate protein folding by ATP-dependent interaction with short
      linear peptide segments that are exposed on unfolded proteins. The mode of action
      of the Escherichia coli homolog DnaK is representative of all HSP70 chaperones,
      including the endoplasmic reticulum variant BiP/GRP78. DnaK has been shown to be
      effective in assisting refolding of a wide variety of prokaryotic and eukaryotic
      proteins, including the alpha-helical homodimeric secretory cytokine interferon
      gamma (IFN-gamma). We screened solid-phase peptide libraries from human and mouse
      IFN-gamma to identify DnaK-binding sites. Conserved DnaK-binding sites were
      identified in the N-terminal half of helix B and in the C-terminal half of helix
      C, both of which are located at the IFN-gamma dimer interface. Soluble peptides
      derived from helices B and C bound DnaK with high affinity in competition assays.
      No DnaK-binding sites were found in the loops connecting the alpha-helices. The
      helix C DnaK-binding site appears to be conserved in most members of the
      superfamily of interleukin (IL)-10-related cytokines that comprises, apart from
      IL-10 and IFN-gamma, a series of recently discovered small secretory proteins,
      including IL-19, IL-20, IL-22/IL-TIF, IL-24/MDA-7 (melanoma differentiation
      associated gene), IL-26/AK155, and a number of viral IL-10 homologs. These
      cytokines belong to a relatively small group of homodimeric proteins with highly
      interdigitated interfaces that exhibit the strongly hydrophobic character of the
      interior core of a single-chain folded domain. We propose that binding of DnaK to
      helix C in the superfamily of IL-10-related cytokines may constitute the hallmark
      of a novel conserved regulatory mechanism in which HSP70-like chaperones assist
      in the formation of a hydrophobic dimeric "folding" interface.

PMID- 11970959
TI  - Dynamics of ligand-induced, Rac1-dependent anchoring of cadherins to the actin
      cytoskeleton.
AB  - Cadherin receptors are key morphoregulatory molecules during development. To
      dissect their mode of action, we developed an approach based on the use of
      myogenic C2 cells and beads coated with an Ncad-Fc ligand, allowing us to mimic
      cadherin-mediated adhesion. We used optical tweezers and video microscopy to
      investigate the dynamics of N-cadherin anchoring within the very first seconds of
      bead-cell contact. The analysis of the bead movement by single-particle tracking
      indicated that N-cadherin molecules were freely diffusive in the first few
      seconds after bead binding. The beads rapidly became diffusion-restricted and
      underwent an oriented rearward movement as a result of N-cadherin anchoring to
      the actin cytoskeleton. The kinetics of anchoring were dependent on ligand
      density, suggesting that it was an inducible process triggered by active cadherin
      recruitment. This anchoring was inhibited by the dominant negative form of Rac1,
      but not that of Cdc42. The Rac1 mutant had no effect on cell contact formation or
      cadherin-catenin complex recruitment, but did inhibit actin recruitment. Our
      results suggest that cadherin anchoring to the actin cytoskeleton is an adhesion
      triggered, Rac1-regulated process enabling the transduction of mechanical forces
      across the cell membrane; they uncover novel aspects of the action of cadherins
      in cell sorting, cell migration, and growth cone navigation.

PMID- 11970960
TI  - The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP
      dependent activation of TGF-beta1.
AB  - Integrins, matrix metalloproteases (MMPs), and the cytokine TGF-beta have each
      been implicated in homeostatic cell behaviors such as cell growth and matrix
      remodeling. TGF-beta exists mainly in a latent state, and a major point of
      homeostatic control is the activation of TGF-beta. Because the latent domain of
      TGF-beta1 possesses an integrin binding motif (RGD), integrins have the potential
      to sequester latent TGF-beta (SLC) to the cell surface where TGF-beta activation
      could be locally controlled. Here, we show that SLC binds to alpha(v)beta8, an
      integrin expressed by normal epithelial and neuronal cells in vivo. This binding
      results in the membrane type 1 (MT1)-MMP-dependent release of active TGF-beta,
      which leads to autocrine and paracrine effects on cell growth and matrix
      production. These data elucidate a novel mechanism of cellular homeostasis
      achieved through the coordination of the activities of members of three major
      gene families involved in cell-matrix interactions.

PMID- 11970961
TI  - Regulation of the Bfa1p-Bub2p complex at spindle pole bodies by the cell cycle
      phosphatase Cdc14p.
AB  - The budding yeast mitotic exit network (MEN) is a GTPase-driven signal
      transduction cascade that controls the release of the phosphatase Cdc14p from the
      nucleolus in anaphase and thereby drives mitotic exit. We show that Cdc14p is
      partially released from the nucleolus in early anaphase independent of the action
      of the MEN components Cdc15p, Dbf2p, and Tem1p. Upon release, Cdc14p binds to the
      spindle pole body (SPB) via association with the Bfa1p-Bub2p GTPase activating
      protein complex, which is known to regulate the activity of the G protein Tem1p.
      Cdc14p also interacts with this GTPase. The association of the MEN component
      Mob1p with the SPB acts as a marker of MEN activation. The simultaneous binding
      of Cdc14p and Mob1p to the SPB in early anaphase suggests that Cdc14p initially
      activates the MEN. In a second, later step, which coincides with mitotic exit,
      Cdc14p reactivates the Bfa1p-Bub2p complex by dephosphorylating Bfa1p. This
      inactivates the MEN and displaces Mob1p from SPBs. These data indicate that
      Cdc14p activates the MEN in early anaphase but later inactivates it through Bfa1p
      dephosphorylation and so restricts MEN activity to a short period in anaphase.

PMID- 11970962
TI  - ARF-GAP-mediated interaction between the ER-Golgi v-SNAREs and the COPI coat.
AB  - In eukaryotic cells, secretion is achieved by vesicular transport. Fusion of such
      vesicles with the correct target compartment relies on SNARE proteins on both
      vesicle (v-SNARE) and the target membranes (t-SNARE). At present it is not clear
      how v-SNAREs are incorporated into transport vesicles. Here, we show that binding
      of ADP-ribosylation factor (ARF)-GTPase-activating protein (GAP) to ER-Golgi v
      SNAREs is an essential step for recruitment of Arf1p and coatomer, proteins that
      together form the COPI coat. ARF-GAP acts catalytically to recruit COPI
      components. Inclusion of v-SNAREs into COPI vesicles could be mediated by direct
      interaction with the coat. The mechanisms by which v-SNAREs interact with COPI
      and COPII coat proteins seem to be different and may play a key role in
      determining specificity in vesicle budding.

PMID- 11970963
TI  - Cutting edge commentary: two B-1 or not to be one.
AB  - B-1 cells differ from conventional B-2 cells both phenotypically and
      functionally. Two seemingly mutually exclusive hypotheses have been proposed to
      explain the origin of B-1 cells. The lineage hypothesis holds that certain B cell
      precursors are destined early on to become B-1 cells. The differentiation
      hypothesis holds that every B cell has the same potential to acquire B-1
      characteristics. Reconsideration of previous studies of transgenic and knockout
      mice, plus recent results identifying differences between splenic and peritoneal
      B-1 cells, point to unexpected complexity in the pathway leading to B-1 status. A
      new paradigm is suggested, in which surface Ig signaling is required for B-1 cell
      production, but in which the signaling threshold and context that lead to B-1
      cell development and/or expansion differ for particular B cell precursors.
      Surface Ig signaling may also produce receptor editing, apoptotic deletion, and
      tolerance induction; how these different outcomes are determined remains
      uncertain.

PMID- 11970964
TI  - Cutting edge: Expression of functional CD137 receptor by dendritic cells.
AB  - Interaction between dendritic cells (DCs) and T cells is a prerequisite for the
      initiation of a T cell response. The molecular nature of this interaction remains
      to be fully characterized. We report in this work that freshly isolated mouse
      splenic DCs and bone marrow-derived DCs express CD137 on the cell surface and in
      soluble form. Triggering CD137 increased the secretion of IL-6 and IL-12 from
      DCs. More importantly, infusion of an agonistic mAb to CD137 into naive mice
      enhanced the ability of DCs to stimulate T cell proliferation in response to both
      alloantigens and a nominal Ag in vitro. This enhancement of DC function is not
      mediated through activation of T cells, because the effect was also observed in
      RAG-1 knockout mice that lack T cells. Our findings implicate CD137 as an
      important receptor involved in the modulation of DC function.

PMID- 11970965
TI  - Cutting edge: Identification of an alternative GATA-3 promoter directing tissue
      specific gene expression in mouse and human.
AB  - The GATA family of transcription factors regulates development of multiple
      tissues. Several GATA factors have two promoters directing distinct tissue
      specific expression. Although GATA-3 acts in both neuronal and thymocyte
      development, no alternative promoter usage has been reported. We examined various
      cell types and tissues for potential alternative GATA-3 transcripts and
      identified an alternative transcript directed by a promoter located 10 kb
      upstream of the recognized promoter. Sequences within this promoter and
      alternative first exon are highly conserved between mouse and human genomes. This
      new promoter is expressed selectively in the brain but is essentially
      undetectable in the thymus. In contrast, the recognized promoter is selectively
      expressed in the thymus but not in the brain. We also observed a gradual increase
      in expression from this new promoter during Th2 development. These results
      indicate that similar to other GATA factors, the GATA-3 gene can be controlled by
      two promoters that may direct lineage- and tissue-specific expression.

PMID- 11970966
TI  - Cutting edge: Regulatory T cells from lung cancer patients directly inhibit
      autologous T cell proliferation.
AB  - Active suppression by T regulatory cells plays an important role in the down
      regulation of T cell responses to foreign and self-Ags. Thus far, the potential
      role of CD4(+)CD25(+) T cells in human tumors has not been reported. In this work
      we show that lung tumors contain large numbers of these cells and that they have
      constitutive high-level expression of CD152 (CTLA-4). Furthermore, the
      CD4(+)CD25(+) T cells mediate potent inhibition of autologous T cell
      proliferation. Finally, regulatory T cells from patient tumors failed to inhibit
      the proliferation of allogeneic T cells. Together these results suggest that the
      CD4(+)CD25(+) T cells found in lung tumors selectively inhibit the host immune
      response and therefore could contribute to the progression of lung cancer.

PMID- 11970967
TI  - Cutting edge: Suppressor of cytokine signaling 3 inhibits activation of NFATp.
AB  - Recent studies have suggested that signaling initiated by the activation of Ag
      receptors and signaling activated through cytokine receptors may be regulated by
      a common set of inhibitory proteins. Suppressor of cytokine signaling 3 (SOCS-3),
      which has previously been demonstrated to inhibit cytokine signaling, is induced
      on TCR ligation. Overexpression of SOCS-3 can inhibit transcription driven by the
      IL-2 promoter in response to T cell activation. This inhibitory activity
      correlates with the suppression of calcineurin-dependent dephosphorylation and
      activation of the IL-2 promoter binding transcription factor, NFATp. Infection of
      primary murine T cells with a retrovirus encoding SOCS-3 blocks their IL-2
      production in response to activation. Interestingly, SOCS-3 was found to
      coimmunoprecipitate with the catalytic subunit of calcineurin. These studies
      suggest that SOCS-3 may regulate T cell function as part of a negative feedback
      loop.

PMID- 11970968
TI  - Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated
      peptides.
AB  - GRP94(gp96) elicits CD8(+) T cell responses against its bound peptides, a process
      requiring access of its associated peptides into the MHC class I cross
      presentation pathway of APCs. Entry into this pathway requires receptor-mediated
      endocytosis, and CD91 (low-density lipoprotein receptor-related protein) has been
      reported to be the receptor mediating GRP94 uptake into APC. However, a direct
      role for CD91 in chaperone-based peptide Ag re-presentation has not been
      demonstrated. We investigated the contribution of CD91 to GRP94 cell surface
      binding, internalization, and trafficking in APCs. Whereas a clear role for CD91
      in alpha(2)-macroglobulin binding and uptake was readily obtained, the addition
      of excess CD91 ligand, activated alpha(2)-macroglobulin, or receptor-associated
      protein, an antagonist of all known CD91 ligands, did not affect GRP94 cell
      surface binding, receptor-mediated endocytosis, or peptide re-presentation. These
      data identify a CD91-independent, GRP94 internalization pathway that functions in
      peptide Ag re-presentation.

PMID- 11970969
TI  - Cutting edge: TCR engagement and triggering in the absence of large-scale
      molecular segregation at the T cell-APC contact site.
AB  - We investigated the functional role of large-scale molecular segregation at the T
      cell-APC contact site during T lymphocyte Ag recognition. Inhibition of CD2-CD58
      interaction markedly affected segregation of CD2 and CD2AP from CD45. Under these
      conditions, Ag-induced calcium mobilization, PKC theta; clustering at the
      immunological synapse, and IFN-gamma production also were inhibited. However,
      early TCR signaling and T cell polarization toward APCs were unaffected. Our
      results indicate that the "raison d'etre" of a large-scale segregation of surface
      molecules and intracellular enzymes and adapters, in Ag-stimulated T cells, is to
      reinforce the assembly of the signal transduction cascade rather than favor TCR
      engagement and triggering.

PMID- 11970970
TI  - Attenuation of experimental allergic encephalomyelitis in complement component 6
      deficient rats is associated with reduced complement C9 deposition, P-selectin
      expression, and cellular infiltrate in spinal cords.
AB  - The role of Ab deposition and complement activation, especially the membrane
      attack complex (MAC), in the mediation of injury in experimental allergic
      encephalomyelitis (EAE) is not resolved. The course of active EAE in normal PVG
      rats was compared with that in PVG rats deficient in the C6 component of
      complement (PVG/C6(-)) that are unable to form MAC. Following immunization with
      myelin basic protein, PVG/C6(-) rats developed significantly milder EAE than
      PVG/C rats. The anti-myelin basic protein response was similar in both strains,
      as was deposition of C3 in spinal cord. C9 was detected in PVG/C rats but not in
      PVG/C6(-), consistent with their lack of C6 and inability to form MAC. In PVG/C6(
      ) rats, the T cell and macrophage infiltrate in the spinal cord was also
      significantly less than in normal PVG/C rats. There was also reduced expression
      of P-selectin on endothelial cells, which may have contributed to the reduced
      cellular infiltrate by limiting migration from the circulation. Assay of cytokine
      mRNA by RT-PCR in the spinal cords showed no differences in the profile of Th1 or
      Th2 cytokines between PVG/C and PVG/C6(-) rats. PVG/C rats also had a greater
      increase in peripheral blood white blood cell, neutrophil, and basophil counts
      than was observed in the PVG/C6(-). These findings suggest that the MAC may have
      a role in the pathogenesis of EAE, not only by Ig-activated MAC injury but also
      via induction of P-selectin on vascular endothelium to promote infiltration of T
      cells and macrophages into the spinal cord.

PMID- 11970971
TI  - Roles of SLC/CCL21 and CCR7 in human kidney for mesangial proliferation,
      migration, apoptosis, and tissue homeostasis.
AB  - The release of chemokines by intrinsic renal cells is an important mechanism for
      the regulation of leukocyte trafficking during renal inflammation. The expression
      of chemokine receptors by intrinsic renal cells such as mesangial cells (MC)
      suggests an expanded role for chemokine-chemokine receptor biology in local
      immunomodulation and potentially glomerular homeostasis. By immunohistochemistry
      we found the chemokine receptor CCR7 expressed in a mesangial pattern while the
      CCR7 ligand SLC/CCL21 showed a podocyte-specific expression. CCR7 expression was
      further characterized by RT-PCR, RNase protection assays, and FACS analysis of
      cultured human MC, and was found to be constitutively present. Real-time PCR of
      microdissected glomeruli confirmed the expression of SLC/CCL21. A functional role
      for CCR7 was demonstrated for human MC migration and proliferation. A protective
      effect of SLC/CCL21 was shown for MC survival in Fas Ab-induced apoptosis.
      Finally, "wound healing" was enhanced in the presence of SLC/CCL21 in an in vitro
      injury model. The constitutive glomerular expression of CCR7 and its ligand
      SLC/CCL21 in adjacent cell types of the human kidney suggests novel biological
      functions of this chemokine/chemokine receptor pair and a potential role in
      processes involved in glomerular homeostasis and regeneration.

PMID- 11970972
TI  - Stromal cell-derived factor 1 (CXCL12) induces human cell migration into human
      lymph nodes transplanted into SCID mice.
AB  - Stromal cell-derived factor 1 (SDF-1; CXCL12), a CXC chemokine, has a primary
      role in signaling the recruitment of hemopoietic stem cell precursors to the bone
      marrow during embryonic development. In postnatal life, SDF-1 is widely expressed
      and is induced in chronically inflamed tissues such as psoriatic skin and the
      rheumatoid synovium, but has also been implicated in the migration of lymphocytes
      to lymphoid organs. To investigate the role of SDF-1 in recirculation and homing
      in vivo, we have developed a model in which human peripheral lymph nodes (huPLN)
      are transplanted into SCID mice. We have shown that huPLN transplants are viable,
      vascularized by the murine circulation that forms functional anastomoses with
      transplant vessels. In addition, grafts retain some features of the
      pretransplantation tissue, such as lymphoid follicles, lymphatic and high
      endothelial venule markers. We also show that SDF-1 is capable of inducing the
      migration of a SDF-1-responsive cell line (U937) and human PBLs from the murine
      circulation into the grafts in a dose-dependent manner, inhibitable by CXCR4
      blockade. The mechanism of action of SDF-1 in this model is independent from that
      of TNF-alpha and does not rely on the up-regulation of adhesion molecules (such
      as ICAM-1) on the graft vascular endothelium. This is the first description of
      huPLN transplantation into SCID mice and of the functional effects of SDF-1 in
      regard to the migration of human cells into huPLN in vivo. This model provides a
      powerful tool to investigate the pathways involved in cell migration into
      lymphoid organs and potentially to target them for therapeutic purposes.

PMID- 11970973
TI  - Orally tolerized T cells are only able to enter B cell follicles following
      challenge with antigen in adjuvant, but they remain unable to provide B cell
      help.
AB  - Although it is well documented that feeding Ag can tolerize or prime systemic
      humoral and cell-mediated immune responses, the mechanisms involved remain
      unclear. Elucidation of these mechanisms remains, in part, complicated by the
      inability to assess responses by individual lymphocyte populations. In the past,
      in vivo studies have examined T cell responses at the gross level by examining
      their ability to support B cell Ab production. However, as the fed Ag has the
      capacity to affect B cells directly, analyzing the functional capacity of a
      single Ag-specific T cell population in vivo has been difficult. Using a double
      adoptive transfer system, we have primed or tolerized T cells, independently of B
      cells with a high dose of fed Ag, and examined the ability of these primed or
      tolerized T cells to support B cell clonal expansion in response to a conjugated
      Ag in vivo. We have been able to show that primed T cells support B cell clonal
      expansion and Ab production whereas tolerized T cells do not. Thus, we have
      provided direct evidence that tolerized T cells are functionally unable to help B
      cells in vivo. Furthermore, we have shown that this inability of tolerized T
      cells to support fulminant B cell responses is not a result of defective clonal
      expansion or follicular migration, since following challenge tolerized T cells
      are similar to primed T cells in both of these functions.

PMID- 11970974
TI  - Fibroblasts from human spleen regulate NK cell differentiation from blood CD34(+)
      progenitors via cell surface IL-15.
AB  - Besides a structural role in tissue architecture, fibroblasts have been shown to
      regulate the proliferation and differentiation of other neighboring specialized
      cell types, but differently according to the anatomic site and pathologic status
      of their tissue of origin. In this study we report a novel regulatory function of
      human spleen-derived fibroblasts in the development of NK cells from adult
      resting blood progenitors. When CD34(+) cells were cocultured with spleen-derived
      fibroblasts in monolayers, nonadherent CD56(+)CD3(-) NK cells were predominantly
      produced after 2-3 wk of culture in the absence of exogenous cytokines. Most NK
      cells expressed class I-recognizing CD94 and NK p46, p44, and p30 receptors as
      well as perforin and granzyme lytic granules. Moreover, these cells demonstrated
      spontaneous killing activity. Cell surface immunophenotyping of spleen-derived
      fibroblasts revealed a low and consistent expression of IL-15, Flt3 ligand, and c
      kit ligand. Additionally, low picogram amounts of the three cytokines were
      produced extracellularly. Neutralizing Abs to IL-15, but not the other two
      ligands, blocked NK cell development. Additionally, suppressing direct contacts
      of CD34(+) progenitors and fibroblasts by microporous membrane abrogated NK cell
      production. We conclude that stromal fibroblasts within the human spleen are
      involved via constitutive cell surface expression of bioactive IL-15 in the
      development of functional activated NK cells under physiologic conditions.

PMID- 11970975
TI  - Prostanoids play a major role in the primary tumor-induced inhibition of
      dendritic cell differentiation.
AB  - Production of immunosuppressive factors is one of the mechanisms by which tumors
      evade immunosurveillance. Soluble factors hampering dendritic cell (DC)
      development have recently been identified in culture supernatants derived from
      tumor cell lines. In this study, we investigated the presence of such factors in
      24-h culture supernatants from freshly excised solid human tumors (colon, breast,
      renal cell carcinoma, and melanoma). While primary tumor-derived supernatant
      (TDSN) profoundly hampered the in vitro DC differentiation from CD14(+) plastic
      adherent monocytes or CD34(+) precursors (based on morphology and CD1a/CD14
      phenotype), the effects of tested tumor cell line-derived supernatants were
      minor. Cyclooxygenase (COX)-1- and COX-2-regulated prostanoids present in the
      primary TDSN were found to be solely responsible for the observed hampered
      differentiation of monocyte-derived DC (MoDC). In contrast, both prostanoids and
      IL-6 were found to contribute to the TDSN-induced inhibition of DC
      differentiation from CD34(+) precursor cells. While the addition of TDSN during
      differentiation interfered with the ability of CD34-derived DC to stimulate a
      primary allogeneic T cell response, it actually increased this ability of MoDC.
      These opposite effects were correlated to different effects of the TDSN on the
      expression levels of CD86 and HLA-DR on the DC from the different precursor
      origins. Although TDSN increased the T cell-stimulatory capacity of MoDC, TDSN
      inhibited the IL-12 production and increased the IL-10 production of MoDC, thus
      skewing them to a type-2 T cell-inducing phenotype. In conclusion, this study
      demonstrates that primary tumors negatively impact DC development and function
      through COX-1 and -2 regulated factors, whereas tumor-derived cell lines may lose
      this ability upon in vitro propagation.

PMID- 11970977
TI  - T cell-dependent maturation of dendritic cells in response to bacterial
      superantigens.
AB  - Dendritic cells (DC) express a set of germline-encoded transmembrane Toll-like
      receptors that recognize shared microbial products, such as Escherichia coli LPS,
      termed pathogen-associated molecular patterns. Analysis of the in vivo response
      to pathogen-associated molecular patterns has uncovered their ability to induce
      the migration and the maturation of DC, favoring thus the delivery of Ag and
      costimulatory signals to naive T cells in vivo. Bacterial superantigens
      constitute a particular class of pathogen-derived molecules known to induce a
      potent inflammatory response in vivo, secondary to the activation of a large
      repertoire of T cells. We demonstrate in this work that Staphylococcal
      superantigens induce migration and maturation of DC populations in vivo. However,
      in contrast to LPS, superantigens failed to induce DC maturation in RAG or MHC
      class II-deficient mice, suggesting that T cell activation was a prerequisite for
      DC maturation. This conclusion was further supported by the finding that T cell
      activation induced by 1) mitogenic anti-CD3 mAbs, 2) allo-MHC determinants, or 3)
      nominal Ag in a TCR-transgenic model induces DC maturation in vivo. These studies
      also revealed that DC that matured in response to T cell mitogens display,
      comparatively to LPS, a distinctive phenotype characterized by high expression of
      the MHC class II, CD40, and CD205 markers, but only moderate (CD86) to minimal
      (CD80) expression of CD28/CTLA4 ligands. This work demonstrates that activation
      of a sufficient number of naive T cells in vivo constitutes a novel form of
      immune danger, functionally linked to DC maturation.

PMID- 11970976
TI  - Transmodulation of BCR signaling by transduction-incompetent antigen receptors:
      implications for impaired signaling in anergic B cells.
AB  - B cell tolerance can be maintained by functional inactivation, or anergy, wherein
      B cell Ag receptors (BCR) remain capable of binding Ag, but are unable to
      transduce signals. Although the molecular mechanisms underlying this
      unresponsiveness are unknown, some models of B cell anergy are characterized by
      disruption of proximal BCR signaling events, and by destabilization of the BCR
      complex. Receptor destabilization is manifest by a reduced ability to
      coimmunoprecipitate membrane Ig with the Ig-alpha/Ig-beta signal-transducing
      complex. To begin to explore the possibility that anergy is the consequence of
      receptor destabilization, we analyzed a panel of B lymphoma transfectants
      expressing constant amounts of signal-competent Ag receptors and varied amounts
      of a receptor with identical specificity, but bearing mutations that render it
      incapable of interacting with Ig-alpha/Ig-beta. This analysis revealed that
      coaggregation of signal-incompetent receptors prevented Ag-induced Ig-alpha and
      Syk phosphorylation, mobilization of Ca(2+), and the up-regulation of CD69
      mediated by competent receptors. In contrast, Ag-induced Cbl and Erk
      phosphorylation were unaffected. Data indicate that coaggregation of destabilized
      receptors (as few as approximately 15% of total) with signal-competent receptors
      significantly affects the ability of competent receptors to transduce signals.
      Thus, BCR destabilization may underlie the Ag unresponsiveness of anergic B
      cells.

PMID- 11970978
TI  - Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans
      cells and dermal dendritic cells from human and murine skin.
AB  - Dendritic cells migrate from the skin to the draining lymph nodes. They transport
      immunogenic MHC-peptide complexes, present them to Ag-specific T cells in the T
      areas, and thus generate immunity. Migrating dendritic cells encounter physical
      obstacles, such as basement membranes and collagen meshwork. Prior work has
      revealed that matrix metalloproteinase-9 (MMP-9) contributes to mouse Langerhans
      cell migration. In this study, we use mouse and human skin explant culture models
      to further study the role of MMPs in the migration and maturation of skin
      dendritic cells. We found that MMP-2 and MMP-9 are expressed on the surface of
      dendritic cells from the skin, but not from other sources. They are also
      expressed in migrating Langerhans cells in situ. The migration of both Langerhans
      cells and dermal dendritic cells is inhibited by a broad spectrum inhibitor of
      MMPs (BB-3103), by Abs to MMP-9 and -2, and by the natural tissue inhibitors of
      metalloproteinases (TIMP), TIMP-1 and TIMP-2. Inhibition by anti-MMP-2 and TIMP-2
      define a functional role for MMP-2 in addition to the previously described
      function of MMP-9. The importance of MMP-9 was emphasized using MMP-9-deficient
      mice in which Langerhans cell migration from skin explants was strikingly
      reduced. However, MMP-9 was only required for Langerhans cell migration and not
      maturation, since nonmigrating Langerhans cells isolated from the epidermis
      matured normally with regard to morphology, phenotype, and T cell stimulatory
      function. These data underscore the importance of MMPs, and they may be of
      relevance for therapeutically regulating dendritic cell migration in clinical
      vaccination approaches.

PMID- 11970979
TI  - Contrasting the roles of costimulation and the natural adjuvant
      lipopolysaccharide during the induction of T cell immunity.
AB  - The requirements for circumventing tolerance induction in favor of memory T cell
      development are poorly understood. Although two signals (Ag and costimulation)
      are necessary to drive effective T cell clonal expansion, few memory T cells
      remain after the response wanes. The adjuvant LPS can increase numbers of long
      lived Ag-specific T cells, but its mechanism of action is not understood. In this
      report, it is shown that LPS, when combined with two-signal stimulation,
      profoundly enhances T cell survival in vivo. This survival does not appear to be
      dependent on the cytokines TNF-alpha, IL-1 beta, IL-6, and IFN-gamma, nor is it
      dependent on the transcription factor NF-kappa B. However, in vivo proliferation
      of NF-kappa B-deficient T cells was comparable to that of wild-type T cells, yet
      their early accumulation in the lymph nodes was severely reduced unless the mice
      were treated with LPS and an agonistic CD40 mAb. Most importantly, we found that
      activation of two different costimulatory signals, CD40 and OX40, could not
      substitute for LPS in rescuing T cells from peripheral deletion. Perhaps
      surprisingly, these data show that LPS delivers a qualitatively different signal
      than multiple costimulatory signals.

PMID- 11970981
TI  - Competition between CTL narrows the immune response induced by prime-boost
      vaccination protocols.
AB  - Recombinant vaccines encoding strings of virus- or tumor-derived peptides and/or
      proteins are currently being designed for use against both cancer and infectious
      diseases. These vaccines aim to induce cytotoxic immune responses against several
      Ags simultaneously. We developed a novel tetramer-based technique, based on
      chimeric HLA A2/H-2K(b) H chains, to directly monitor the CTL response to such
      vaccines in HLA-A2 transgenic mice. We found that priming and boosting with the
      same polyepitope construct induced immune responses that were dominated by CTL of
      a single specificity. When a mixture of viruses encoding single proteins was used
      to boost the polyepitope primed response, CTL of multiple specificities were
      simultaneously expanded to highly effective levels in vivo. In addition, we show
      that a preexisting response to one of the epitopes encoded within a polyepitope
      construct significantly impaired the ability of the vaccine to expand CTL of
      other specificities. Our findings define a novel vaccination strategy optimized
      for the induction of an effective polyvalent cytotoxic response.

PMID- 11970982
TI  - Generation of CD4(+)CD25(+) regulatory T cells from autoreactive T cells
      simultaneously with their negative selection in the thymus and from
      nonautoreactive T cells by endogenous TCR expression.
AB  - Normal T cell repertoire contains regulatory T cells that control autoimmune
      responses in the periphery. One recent study demonstrated that CD4(+)CD25(+) T
      cells were generated from autoreactive T cells without negative selection.
      However, it is unclear whether, in general, positive selection and negative
      selection of autoreactive T cells are mutually exclusive processes in the thymus.
      To investigate the ontogeny of CD4(+)CD25(+) regulatory T cells, neo-autoantigen
      bearing transgenic mice expressing chicken egg OVA systemically in the nuclei (Ld
      nOVA) were crossed with transgenic mice expressing an OVA-specific TCR (DO11.10).
      Ld-nOVA x DO11.10 mice had increased numbers of CD4(+)CD25(+) regulatory T cells
      in the thymus and the periphery despite clonal deletion. In Ld-nOVA x DO11.10
      mice, T cells expressing endogenous TCR alpha beta chains were CD4(+)CD25(-) T
      cells, whereas T cells expressing autoreactive TCR were selected as CD4(+)CD25(+)
      T cells, which were exclusively dominant in recombination-activating gene 2
      deficient Ld-nOVA x DO11.10 mice. In contrast, in DO11.10 mice, CD4(+)CD25(+) T
      cells expressed endogenous TCR alpha beta chains, which disappeared in
      recombination-activating gene 2-deficient DO11.10 mice. These results indicate
      that part of autoreactive T cells that have a high affinity TCR enough to cause
      clonal deletion could be positively selected as CD4(+)CD25(+) T cells in the
      thymus. Furthermore, it is suggested that endogenous TCR gene rearrangement might
      critically contribute to the generation of CD4(+)CD25(+) T cells from
      nonautoreactive T cell repertoire, at least under the limited conditions such as
      TCR-transgenic models, as well as the generation of CD4(+)CD25(-) T cells from
      autoreactive T cell repertoire.

PMID- 11970980
TI  - On CD28/CD40 ligand costimulation, common gamma-chain signals, and the alloimmune
      response.
AB  - Activation and robust expansion of naive T cells often require T cell
      costimulatory signals and T cell growth factors. However, the precise growth and
      costimulation requirements for activation and expansion of CD4(+) and CD8(+) T
      cells in vivo in allograft response are still not clearly defined. In the present
      study, we critically examined the role of CD28/CD40 ligand (CD40L) costimulation
      and the common gamma-chain (gamma(c)) signals, a shared signaling component by
      receptors for all known T cell growth factors (i.e., IL-2, IL-4, IL-7, IL-9, IL
      15, IL-21), in activation and expansion of CD4(+) and CD8(+) T cells in the
      allogeneic hosts. We found that CD28/CD40L costimulation and the gamma(c) signals
      are differentially involved in proliferation and clonal expansion of CD4(+) and
      CD8(+) T cells in response to alloantigen stimulation. CD8(+) T cells are highly
      dependent on the gamma(c) signals for survival, expansion, and functional
      maturation, whereas in vivo expansion of alloreactive CD4(+) T cells is largely
      gamma(c) independent. T cell costimulation via CD28 and CD40L, however, is
      necessary and sufficient for activation and expansion of CD4(+) T cells in vivo.
      In a skin transplant model, blocking both CD28/CD40L and the gamma(c) pathways
      induced prolonged skin allograft survival. Our study provides critical insights
      that the CD4 and CD8 compartments are most likely governed by distinct mechanisms
      in vivo, and targeting both costimulatory and gamma(c) signals may be highly
      effective in certain cytopathic conditions involving activation of both CD4(+)
      and CD8(+) T cells.

PMID- 11970983
TI  - NF-kappa B2 is required for optimal CD40-induced IL-12 production but dispensable
      for Th1 cell Differentiation.
AB  - NF-kappa B is a ubiquitously expressed transcription factor involved in the
      regulation of innate and adaptive immunity. As part of studies to define the role
      of various NF-kappa B family members in Th cell development and maintenance, we
      infected NF-kappa B2(-/-) and control mice with Leishmania major and followed
      disease progression. NF-kappa B2(-/-) mice on a normally resistant background
      develop chronic nonhealing lesions associated with uncontrolled parasite
      replication and a failure to develop an IFN-gamma response. We show that there
      are no intrinsic defects in Th cell differentiation in the absence of NF-kappa
      B2. Indeed, NF-kappa B2(-/-) T cells are able to develop a Th1 phenotype and
      protect recombination-activating gene(-/-) mice from progressive cutaneous
      leishmaniasis. We demonstrate instead that the susceptibility of NF-kappa B2(-/-)
      mice to L. major is the result of an IL-12 deficiency, and we provide evidence
      for a specific impairment in CD40-induced IL-12 production by macrophages lacking
      this transcription factor.

PMID- 11970984
TI  - Aberrant expression of Fas ligand in mice deficient for the MHC class II
      transactivator.
AB  - The MHC class II transactivator (CIITA) is a critical regulator of MHC class II
      genes and other genes involved in the Ag presentation pathway. CIITA-deficient
      mice lack MHC class II expression on almost all APCs. In this study, we show that
      these mice also have aberrant Fas ligand expression on both CD4 T cells and B
      cells. We found that Fas ligand expression was greatly increased on CIITA
      deficient CD4 T cells during the Th1 differentiation process. However, both CIITA
      deficient and control Th1 effector cells up-regulated Fas ligand to similar
      levels if cells were reactivated. The introduction of CIITA into primary CD4 T
      cells via retroviral infection resulted in a reduction in the level of Fas ligand
      and delay in apoptosis after activation. Interestingly, activated B cells from
      the CIITA-deficient mice also showed increased levels of Fas ligand that could be
      to some degree inhibited by the introduction of IL-4.

PMID- 11970985
TI  - CTLA-4 suppresses proximal TCR signaling in resting human CD4(+) T cells by
      inhibiting ZAP-70 Tyr(319) phosphorylation: a potential role for tyrosine
      phosphatases.
AB  - The balance between positive and negative signals plays a key role in determining
      T cell function. CTL-associated Ag-4 is a surface receptor that can inhibit T
      cell responses induced upon stimulation of the TCR and its CD28 coreceptor.
      Little is known regarding the signaling mechanisms elicited by CTLA-4. In this
      study we analyzed CTLA-4-mediated inhibition of TCR signaling in primary resting
      human CD4(+) T cells displaying low, but detectable, CTLA-4 cell surface
      expression. CTLA-4 coligation with the TCR resulted in reduced downstream protein
      tyrosine phosphorylation of signaling effectors and a striking inhibition of
      extracellular signal-regulated kinase 1/2 activation. Analysis of proximal TCR
      signaling revealed that TCR zeta-chain phosphorylation and subsequent zeta
      associated protein of 70 kDa (ZAP-70) tyrosine kinase recruitment were not
      significantly affected by CTLA-4 engagement. However, the association of p56(lck)
      with ZAP-70 was inhibited following CTLA-4 ligation, correlating with reduced
      actions of p56(lck) in the ZAP-70 immunocomplex. Moreover, CTLA-4 ligation caused
      the selective inhibition of CD3-mediated phosphorylation of the positive
      regulatory ZAP-70 Y319 site. In addition, we demonstrate protein tyrosine
      phosphatase activity associated with the phosphorylated CTLA-4 cytoplasmic tail.
      The major phosphatase activity was attributed to Src homology protein 2 domain
      containing tyrosine phosphatase 1, a protein tyrosine phosphatase that has been
      shown to be a negative regulator of multiple signaling pathways in hemopoietic
      cells. Collectively, our findings suggest that CTLA-4 can act early during the
      immune response to regulate the threshold of T cell activation.

PMID- 11970986
TI  - Downstream of kinase, p62(dok), is a mediator of Fc gamma IIB inhibition of Fc
      epsilon RI signaling.
AB  - The low-affinity receptor for IgG, Fc gamma RIIB, is expressed widely in the
      immune system and functions to attenuate Ag-induced immune responses. In mast
      cells, coaggregation of Fc gamma RIIB with the high-affinity IgE receptor, Fc
      epsilon RI, leads to inhibition of Ag-induced degranulation and cytokine
      production. Fc gamma RIIB inhibitory activity requires a conserved motif within
      the Fc gamma RIIB cytoplasmic domain termed the immunoreceptor tyrosine-based
      inhibition motif. When coaggregated with an activating receptor (e.g., Fc epsilon
      RI, B cell Ag receptor), Fc gamma RIIB is rapidly phosphorylated on tyrosine and
      recruits the SH2 domain-containing inositol 5-phosphatase (SHIP). However, the
      mechanisms by which SHIP mediates Fc gamma RIIB inhibitory function in mast cells
      remain poorly defined. In this report we demonstrate that Fc gamma RIIB
      coaggregation with Fc epsilon RI stimulates enhanced SHIP tyrosine
      phosphorylation and association with Shc and p62(dok). Concurrently, enhanced
      p62(dok) tyrosine phosphorylation and association with RasGAP are observed,
      suggesting that SHIP may mediate Fc gamma RIIB inhibitory function in mast cells
      via recruitment of p62(dok) and RasGAP. Supporting this hypothesis, recruitment
      of p62(dok) to Fc epsilon RI is sufficient to inhibit Fc epsilon RI-induced
      calcium mobilization and extracellular signal-regulated kinase 1/2 activation.
      Interestingly, both the amino-terminal pleckstrin homology and phosphotyrosine
      binding domains and the carboxyl-terminal proline/tyrosine-rich region of
      p62(dok) can mediate inhibition, suggesting activation of parallel downstream
      signaling pathways that converge at extracellular signal-regulated kinase 1/2
      activation. Finally, studies using gene-ablated mice indicate that p62(dok) is
      dispensable for Fc gamma RIIB inhibitory signaling in mast cells. Taken together,
      these data suggest a role for p62(dok) as a mediator of Fc gamma RIIB inhibition
      of Fc epsilon RI signal transduction in mast cells.

PMID- 11970987
TI  - CD28 costimulation induces delta opioid receptor expression during anti-CD3
      activation of T cells.
AB  - Previous studies have demonstrated that naive splenic mouse T cells express no or
      only very low levels of the delta-type opioid receptor (delta OR), but
      stimulation of mouse splenocytes with Con A results in induction of delta OR mRNA
      and protein. In this report we have shown that stimulation of highly purified
      populations of naive mouse T cells with anti-CD3 mAb alone results in T cell
      activation, as evidenced by sustained IL-2 secretion and cell proliferation, but
      fails to elicit delta OR expression. However, delta OR expression is induced by
      costimulation of these very pure T cells with anti-CD3 and anti-CD28 mAbs. The
      delta OR induction by anti-CD3 and anti-CD28 costimulation was completely blocked
      by inhibition of phosphatidylinositol 3-kinase with wortmannin. Because
      phosphatidylinositol 3-kinase activation in T cells is linked to costimulation,
      these results suggest that induction of delta OR expression during T cell
      activation is strictly dependent on costimulation. It also appears that
      costimulatory receptors other than CD28 can provide the signaling required for
      delta OR expression because delta OR mRNA was induced by Con A stimulation of
      splenocytes from CD28-deficient mice.

PMID- 11970989
TI  - Generation of CD8(+) T cell memory in response to low, high, and excessive levels
      of epitope.
AB  - The magnitude of a virus-specific memory CTL population can dramatically
      influence the outcome of secondary infections, yet little is known about the
      determinants of memory size. We investigated the impact of epitope levels on CTL
      memory generation by using a recombinant vaccinia virus system that allows for a
      broad range of epitope expression with the same infectious dose of virus. The
      size of the memory pool was examined using MHC class I/peptide tetramer staining
      and IFN-gamma ELISPOT analysis following priming with viruses expressing low,
      high, or excessive epitope levels. The size of the epitope-specific CD8(+) T cell
      memory population correlates with Ag dose at the low and high levels of epitope
      expression. However, at excessive epitope levels, the number of functional, IFN
      gamma-producing, epitope-specific memory cells is significantly reduced compared
      with the number of tetramer(+) cells. These results demonstrate that the level of
      epitope expressed during an acute viral infection in vivo can dramatically
      influence CTL memory size. Furthermore, when epitope is overexpressed, the
      quality of the response can be adversely affected. Therefore, epitope expression
      level is an important consideration when developing approaches to optimize CTL
      memory induction.

PMID- 11970988
TI  - Prostaglandin E(2) inhibits IL-18-induced ICAM-1 and B7.2 expression through
      EP2/EP4 receptors in human peripheral blood mononuclear cells.
AB  - Costimulatory molecules play important roles in immune responses. In the present
      study we investigated the effects of PGE(2) on the expression of ICAM-1, B7.1,
      and B7.2 on monocytes in IL-18-stimulated PBMC using FACS analysis. Addition of
      PGE(2) to PBMC inhibited ICAM-1 and B7.2 expression elicited by IL-18 in a
      concentration-dependent manner. We examined the involvement of four subtypes of
      PGE(2) receptors, EP1, EP2, EP3, and EP4, in the modulatory effect of PGE(2) on
      ICAM-1 and B7.2 expression elicited by IL-18, using subtype-specific agonists.
      ONO-AE1-259-01 (EP2R agonist) inhibited IL-18-elicited ICAM-1 and B7.2 expression
      in a concentration-dependent manner with a potency slightly less than that of
      PGE(2), while ONO-AE1-329 (EP4R agonist) was much less potent than PGE(2). The
      EP2/EP4R agonist 11-deoxy-PGE(1) mimicked the effect of PGE(2) with the same
      potency. ONO-D1-004 (EP1R agonist) and ONO-AE-248 (EP3R agonist) showed no effect
      on IL-18-elicited ICAM-1 or B7.2 expression. These results indicated that EP2 and
      EP4Rs were involved in the action of PGE(2). Dibutyryl cAMP and forskolin down
      regulated ICAM-1 and B7.2 expression in IL-18-stimulated monocytes. As EP2 and
      EP4Rs are coupled to adenylate cyclase, we suggest that PGE(2) down-regulates IL
      18-induced ICAM-1 and B7.2 expression in monocytes via EP2 and EP4Rs by cAMP
      dependent signaling pathways. The fact that anti-B7.2 as well as anti-ICAM-1 Ab
      inhibited IL-18-induced cytokine production implies that PGE(2) may modulate the
      immune response through regulation of the expression of particular adhesion
      molecules on monocytes via EP2 and EP4Rs.

PMID- 11970990
TI  - Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces
      CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells.
AB  - Alefacept, an immunomodulatory recombinant fusion protein composed of the first
      extracellular domain of LFA-3 fused to the human IgG1 hinge, C(H)2, and C(H)3
      domains, has recently been shown in phase II and III clinical trials to safely
      reduce disease expression in patients with chronic plaque psoriasis. Alefacept
      modulates the function of and selectively induces apoptosis of CD2(+) human
      memory-effector T cells in vivo. We have sought to gain further understanding of
      the mechanisms of action that influence the biological activity of alefacept and
      may contribute to its efficacy and patient responsiveness. Specifically evaluated
      is the ability of alefacept to activate intracellular signals mediated via CD2
      and/or Fc gamma RIII (CD16). Experimentation using isoforms of alefacept
      engineered to have amino acid substitutions in the IgG1 C(H)2 domain that impact
      Fc gamma R binding indicate that alefacept mediates cognate interactions between
      cells expressing human CD2 and CD16 to activate cells, e.g., increase
      extracellular signal-regulated kinase phosphorylation, up-regulate cell surface
      expression of the activation marker CD25, and induce release of granzyme B. In
      the systems used, this signaling is shown to require binding to CD2 and CD16 and
      be mediated through CD16, but not CD2. Experimentation using human CD2-transgenic
      mice and isoforms of alefacept confirmed the requirement for Fc gamma R binding
      for detection of the pharmacological effects of alefacept in vivo. Thus alefacept
      acts as an effector molecule, mediating cognate interactions to activate Fc gamma
      R(+) cells (e.g., NK cells) to induce apoptosis of sensitive CD2(+) target cells.

PMID- 11970991
TI  - A role for IFN-gamma in primary and secondary immunity generated by NK cell
      sensitive tumor-expressing CD80 in vivo.
AB  - We have investigated the primary and secondary immunity generated in vivo by a
      MHC class I-deficient tumor cell line that expressed CD80 (B7-1). CD80 expression
      enhanced primary NK cell-mediated tumor rejection in vivo and T cell immunity
      against secondary tumor challenge. CD80 expression enhanced primary NK cell
      mediated tumor rejection, and both NK cell perforin and IFN-gamma activity were
      critical for the rejection of MHC class I-deficient RMA-S-CD80 tumor cells. This
      primary rejection process stimulated the subsequent development of specific CTL
      and Th1 responses against Ags expressed by the MHC class I-deficient RMA-S tumor
      cells. The development of effective secondary T cell immunity could be elicited
      by irradiated RMA-S-CD80 tumor cells and was dependent upon NK cells and IFN
      gamma in the priming response. Our findings demonstrate a key role for IFN-gamma
      in innate and adaptive immunity triggered by CD80 expression on tumor cells.

PMID- 11970992
TI  - The Src family kinase Fyn mediates signals induced by TCR antagonists.
AB  - FcR nonbinding anti-CD3 epsilon mAbs elicit partial TCR signaling that leads to T
      cell unresponsiveness and tolerance in vivo. In this study, the membrane-proximal
      events that promote T cell inactivation by FcR nonbinding anti-CD3 mAbs were
      examined. In the context of FcR nonbinding anti-CD3, TCR complexes did not
      aggregate and failed to translocate into glycolipid-enriched membrane
      microdomains. Furthermore, FcR nonbinding anti-CD3 mAbs induced tyrosine
      phosphorylation of the Fyn substrate Cbl, but not the ZAP-70 substrate linker for
      activation of T cells. Overexpression of Fyn, but not Lck, restored the
      mitogenicity of FcR nonbinding anti-CD3 in primary T cells. Taken together, these
      results suggest that Fyn mediates the partial signaling induced by TCR
      antagonists.

PMID- 11970993
TI  - IFN regulatory factor-1 regulates IFN-gamma-dependent cathepsin S expression.
AB  - Cathepsin S is a cysteine protease with potent endoproteolytic activity and a
      broad pH profile. Cathepsin S activity is essential for complete processing of
      the MHC class II-associated invariant chain within B cells and dendritic cells,
      and may also be important in extracellular matrix degradation in atherosclerosis
      and emphysema. Unique among cysteine proteases, cathepsin S activity is up
      regulated by IFN-gamma. Given its importance, we sought to elucidate the pathway
      by which IFN-gamma increases cathepsin S expression. Our data demonstrate that
      the cathepsin S promoter contains an IFN-stimulated response element (ISRE) that
      is critical for IFN-gamma-induced gene transcription in a cell line derived from
      type II alveolar epithelial (A549) cells. IFN response factor (IRF)-2 derived
      from A549 nuclear extracts associates with the ISRE oligonucleotide in gel shift
      assays, but is quickly replaced by IRF-1 following stimulation with IFN-gamma.
      The time course of IRF-1/ISRE complex formation correlates with increased levels
      of IRF-1 protein and cathepsin S mRNA. Overexpression of IRF-1, but not IRF-2,
      markedly augments cathepsin S promoter activity in A549 cells. Furthermore,
      overexpression of IRF-1 increases endogenous cathepsin S mRNA levels in 293T
      epithelial cells. Finally, freshly isolated bone marrow cells from IRF-1(-/-)
      mice fail to up-regulate cathepsin S activity in response to IFN-gamma. Thus, IRF
      1 is the critical transcriptional mediator of IFN-gamma-dependent cathepsin S
      activation. These data elucidate a new pathway by which IRF-1 may affect MHC
      class II processing and presentation.

PMID- 11970994
TI  - Vitamin A enhances in vitro Th2 development via retinoid X receptor pathway.
AB  - Vitamin A deficiency diminishes Th2-mediated Ab responses, and high-level dietary
      vitamin A or treatment with the vitamin A metabolite retinoic acid (RA) enhances
      such responses. To identify a potential mechanism(s) underlying this in vivo
      activity of vitamin A, we examined the effects of all-trans and 9-cis RA on
      development of Th1 and Th2 cell populations using in vitro stimulation of Ag
      naive Th0 cells from the DO11.10 TCR-transgenic mouse. Treatment with 9-cis, but
      not with all-trans RA, at primary stimulation strongly enhanced Th2 development.
      IL-4-neutralizing Ab blocked this activity, but IL-12- and IFN-gamma-neutralizing
      Ab did not. Because 9-cis RA regulates gene transcription via either RA receptors
      or retinoid X receptors (RXRs), we tested the Th2-enhancing activities of the RXR
      and RA receptor-selective agonists AGN194204 and 4-((E)-2-(5,6,7,8-tetrahydro
      5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid (TTNPB). AGN194204
      strongly enhanced Th2 development, whereas TTNPB did not. This RXR agonist also
      enhanced Th2 development when purified, naive Th0 cells (L-selectin(high)/CD4(+))
      were stimulated with CD3 and CD28 Abs in the absence of APCs. During primary
      antigenic stimulation of naive Th0 cells from DO11.10 mice, AGN194204 increased
      IL-4 and IL-5 production, decreased IFN-gamma production, increased mRNA in
      responding T cells for genes involved in Th2 development (IL-4, GATA-3, and c
      maf), and decreased mRNA for genes involved in Th1 development (IFN-gamma, T-bet,
      and IL-12R). These data show that stimulation of the RXR pathway enhances Th2
      development, perhaps by affecting the relative expression of pertinent
      transcription factors, cytokines, and cytokine receptors.

PMID- 11970995
TI  - Tissue-level regulation of Th1 and Th2 primary and memory CD4 T cells in response
      to Listeria infection.
AB  - Ag-specific Th1 and Th2 cytokine-producing CD4 T cells were quantitated in
      secondary lymphoid and tertiary tissues following oral Listeria monocytogenes
      infection. Although the response to Listeria was previously believed to be
      predominantly Th1 like, CD4 T cells producing IL-4 or IL-5 comprised a
      substantial proportion of the overall primary and memory response. The frequency
      of IFN-gamma-, IL-4-, or IL-5-producing primary effector or memory CD4 T cells
      was significantly higher in lung, liver, and intestinal lamina propria (LP) as
      compared with spleen and lymph node. However, maximum numbers of IL-4- and IL-5
      producing cells were detected in the LP several days after the peak of the Th1
      response, and IL-5 production was skewed toward the mucosal tissues. Remarkably,
      the recall response resulted in sustained Th1 and Th2 responses in tertiary, but
      not lymphoid tissues and long-term retention of Th1 and Th2 memory cells in equal
      proportions in the LP. Finally, CD40 ligand was essential for induction of IFN
      gamma in the spleen and LP, but not in the liver and lung, while the IL-4
      response required CD40 ligand only in the spleen. Therefore, the rules governing
      the effector phenotype, and the overall magnitude of the CD4 response, are
      regulated at the level of individual tissues.

PMID- 11970997
TI  - The CD3 gamma leucine-based receptor-sorting motif is required for efficient
      ligand-mediated TCR down-regulation.
AB  - TCR down-regulation plays an important role in modulating T cell responses both
      during T cell development and in mature T cells. At least two distinct pathways
      exist for down-regulation of the TCR. One pathway is activated following TCR
      ligation and is dependent on tyrosine phosphorylation. The other pathway is
      dependent on protein kinase C (PKC)-mediated activation of the CD3 gamma di
      leucine-based receptor-sorting motif. Previous studies have failed to demonstrate
      a connection between ligand- and PKC-induced TCR down-regulation. Thus, although
      an apparent paradox, the dogma has been that ligand- and PKC-induced TCR down
      regulations are not interrelated. By analyses of a newly developed CD3 gamma
      negative T cell variant, freshly isolated and PHA-activated PBMC, and a mouse T
      cell line, we challenged this dogma and demonstrate in this work that PKC
      activation and the CD3 gamma di-leucine-based motif are indeed required for
      efficient ligand-induced TCR down-regulation.

PMID- 11970996
TI  - Expression of the tyrosine phosphatase SRC homology 2 domain-containing protein
      tyrosine phosphatase 1 determines T cell activation threshold and severity of
      experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a CD4 Th1-mediated
      inflammatory demyelinating disorder of the CNS and a well-established animal
      model for multiple sclerosis. Src homology 2 domain-containing protein tyrosine
      phosphatase 1 (SHP-1) is a cytosolic tyrosine phosphatase that is involved in
      regulating the T cell activation cascade from signals initiated through the TCR.
      To study the role of SHP-1 in EAE pathogenesis, we immunized B10.PL mice
      heterozygous for deletion of the SHP-1 gene (me(v+/-)) and B10.PL wild-type mice
      with the immunodominant epitope of myelin basic protein (MBP Ac1-11). T cell
      proliferation and IFN-gamma production were significantly increased in me(v+/-)
      mice after immunization with MBP Ac1-11. The frequency of MBP Ac1-11-specific CD4
      T cells, analyzed by staining with fluorescently labeled tetramers (MBP1-11[4Y]:
      I-A(u) complexes), was increased in the draining lymph node cells of me(v+/-)
      mice compared with wild-type mice. In addition, me(v+/-) mice developed a more
      severe course of EAE with epitope spreading to proteolipid protein peptide 43-64.
      Finally, expansion of MBP Ac1-11-specific T cells in response to Ag was enhanced
      in me(v+/-) T cells, particularly at lower Ag concentrations. These data
      demonstrate that the level of SHP-1 plays an important role in regulating the
      activation threshold of autoreactive T cells.

PMID- 11970998
TI  - Toll-like receptor 4 is required for optimal development of Th2 immune responses:
      role of dendritic cells.
AB  - LPS potently induces dendritic cell maturation and the production of
      proinflammatory cytokines, such as IL-12, by activation of Toll-like receptor 4
      (TLR4). Since IL-12 is important for the generation and maintenance of Th1
      responses and may also inhibit Th2 cell generation from naive CD4 T cell
      precursors, it has been inferred that TLR4 signaling would have similar effects
      via the induction of IL-12 secretion. Surprisingly, we found that TLR4-defective
      mice subjected to sensitization and pulmonary challenge with a protein allergen
      had reductions in airway inflammation with eosinophils, allergen-specific IgE
      levels, and Th2 cytokine production, compared with wild-type mice. These reduced
      responses were attributable, at least in part, to decreased dendritic cell
      function: Dendritic cells from TLR4-defective mice expressed lower levels of
      CD86, a costimulatory molecule important for Th2 responses. They also induced
      less Th2 cytokine production by antigenically naive CD4 T cells in vitro and
      mediated diminished CD4 T cell Ag-specific pulmonary inflammation in vivo. These
      results indicate that TLR4 is required for optimal Th2 responses to Ags from
      nonpathogenic sources and suggest a role for TLR4 ligands, such as LPS derived
      from commensal bacteria or endogenously derived ligands, in maturation of the
      innate immune system before pathogen exposure.

PMID- 11971000
TI  - Friend of GATA is expressed in naive Th cells and functions as a repressor of
      GATA-3-mediated Th2 cell development.
AB  - The commitment of naive T cells to polarized Th cells requires specific changes
      in their transcription factors. Retrovirally overexpressed GATA-3 has been
      reported to induce the Th2 cytokine profile in developing Th1 cells. In this
      study, we examined the role of the N-terminal finger (Nf) of GATA-3 in Th2 cell
      development. The Nf, as well as the C-terminal finger and the transactivation
      domain, is critical for the induction of the Th2 phenotype. Using the GATA-3-Nf
      as a bait, our yeast two-hybrid screening identified friend of GATA (FOG) in the
      Th2 cell-specific library. Naive T cells express significant levels of FOG mRNA,
      which was rapidly down-regulated upon commitment to both Th1 and Th2 lineages. In
      reporter assays, FOG blocked the GATA-3-mediated activation of several cytokine
      promoters. Finally, retroviral expression of FOG in developing Th2 cells
      suppressed both IL-4 and IL-5 and allowed for IFN-gamma production, which was
      accompanied by a significant level of T-bet mRNA expression. Serial deletion
      mutation analysis indicated that the N-terminal region, but not the consensus C
      terminal binding protein-binding motif, of FOG is critical for the effects. Our
      results clearly indicate that 1) FOG is a repressor of GATA-3 in naive T cells
      and 2) the down-regulation of FOG induces Th2 cell differentiation by releasing
      GATA-3 from its repression.

PMID- 11970999
TI  - Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of
      human peripheral blood mononuclear cells and sensitivity to CpG
      oligodeoxynucleotides.
AB  - The Toll-like receptor (TLR)9 is critical for the recognition of
      immunostimulatory CpG motifs but may cooperate with other TLRs. We analyzed TLR1
      10 mRNA expression by using quantitative real-time PCR in highly purified subsets
      of human PBMC and determined the sensitivity of these subsets to CpG
      oligodeoxynucleotides (ODN). TLR1 and TLR6 were expressed in all cell types
      examined. TLR10 was highly expressed in B cells and weakly expressed in
      plasmacytoid dendritic cells (PDC). High expression of TLR2 was characteristic
      for monocytes. PDC and B cells expressed marked levels of TLR7 and TLR9 and were
      directly sensitive to CpG ODN. In CpG ODN-stimulated PDC and B cells, TLR9
      expression rapidly decreased, as opposed to TLR7, which was up-regulated in PDC
      and decreased in B cells. In monocytes, NK cells, and T cells, TLR7 was absent.
      Despite low expression of TLR9, monocytes, NK cells, and T cells did not respond
      to CpG ODN in the absence of PDC but were activated in the presence of PDC. In
      conclusion, our studies provide evidence that PDC and B cells, but not monocytes,
      NK cells, or T cells, are primary targets of CpG ODN in peripheral blood. The
      characteristic expression pattern of TLR1-10 in cellular subsets of human PBMC is
      consistent with the concept that TLR9 is essential in the recognition of CpG ODN
      in PDC and B cells. In addition, selective regulation of TLR7 expression in PDC
      and B cells by CpG ODN revealed TLR7 as a candidate TLR potentially involved in
      modulating the recognition of CpG motifs.

PMID- 11971002
TI  - Dominant effects of mutations in the collagenous domain of mannose-binding
      protein.
AB  - Individuals heterozygous for mutant alleles encoding serum mannose-binding
      protein (MBP, also known as mannose-binding lectin) show increased susceptibility
      to infections caused by a wide range of pathogenic microorganisms. To investigate
      the molecular defects associated with heterozygosity, wild-type rat serum MBP
      polypeptides (MBP-A: 56% identical in sequence to human MBP) and rat MBP
      polypeptides containing mutations associated with human immunodeficiency have
      been coexpressed using a well-characterized mammalian expression system. The
      resulting proteins are secreted almost exclusively as heterooligomers that are
      defective in activating the complement cascade. Functional defects are caused by
      structural changes to the N-terminal collagenous and cysteine-rich domains of
      MBP, disrupting interactions with associated serine proteases. The dominant
      effects of the mutations demonstrate how the presence of a single mutant allele
      gives rise to the molecular defects that lead to the disease phenotype in
      heterozygous individuals.

PMID- 11971001
TI  - Regulation of human Fc epsilon RI alpha-chain gene expression by multiple
      transcription factors.
AB  - Transcriptional regulation of the gene-encoding human Fc epsilon RI alpha-chain
      was analyzed in detail. EMSA revealed that either YY1 or PU.1 bound to the region
      close to that recognized by Elf-1. The alpha-chain promoter activity was up
      regulated approximately 2-fold by exogenously expressed YY1 or PU.1 and
      approximately 7-fold by GATA-1, respectively, in KU812 cells. In contrast,
      coexpression of GATA-1 with either of PU.1 or YY1 dramatically activated the
      promoter approximately 41- or approximately 27-fold, respectively. Especially
      synergic activation by GATA-1 and PU.1 was surprising, because these
      transcription factors are known to inhibit the respective transactivating
      activities of each other. These up-regulating effects of PU.1 and YY1 with GATA-1
      were inhibited by overexpression of Elf-1, indicating that Elf-1 serves as a
      repressor for the alpha-chain gene expression. Transcriptional regulation of the
      alpha-chain gene through four transcriptional factors is discussed.

PMID- 11971003
TI  - Signaling pathways involved in IL-8-dependent activation of adhesion through Mac
      1.
AB  - In human neutrophils, IL-8 induces chemotaxis, the respiratory burst, and granule
      release, and enhances cellular adhesion, a beta(2) integrin-dependent event. IL-8
      stimulates neutrophil adhesion to purified fibrinogen in a Mac-1-dependent
      manner. Mitogen-activated protein kinase (MAPK) activation was detected in human
      neutrophil lysates after treatment with IL-8 and PMA, but not the activating mAb
      CBR LFA 1/2. IL-8-stimulated neutrophil adhesion to fibrinogen was blocked 50% by
      the MAPK/extracellular signal-related kinase-activating enzyme inhibitor
      PD098059. Adhesion was blocked approximately 75% by inhibition of the
      phosphatidylinositol-3 kinase (PI3K) pathway with LY294002, supporting that
      activation of both MAPK and PI3K may play a role in IL-8-dependent inside-out
      signals that activate Mac-1. Activation of MAPK was inhibited in IL-8-stimulated
      cells in the presence of PI3K inhibitors LY294002 or wortmannin, supporting a
      model in which PI3K is upstream of MAPK. IL-8-stimulated neutrophil adhesion was
      inhibited 50% by bisindolylmaleimide-I, implicating protein kinase C (PKC) in the
      intracellular signaling from the IL-8R to Mac-1. A 74-kDa molecular mass species
      was detected by an activation-specific Ab to PKC when cells were stimulated with
      PMA or IL-8, but not a beta(2)-activating Ab. Inhibition of either MAPK or PKC
      resulted in partial inhibition of IL-8-stimulated polymorphonuclear neutrophil
      adhesion, and treatment with both inhibitors simultaneously completely abolished
      IL-8-stimulated adhesion to ligand. Inhibition of PI3K blocked MAPK activation,
      but not PKC activation, suggesting a branch point that precedes PI3K activation.
      These data suggest that both MAPK and PKC are activated in response to IL-8
      stimulation, and that these may represent independent pathways for beta(2)
      integrin activation in neutrophils.

PMID- 11971004
TI  - Stat5B shuttles between cytoplasm and nucleus in a cytokine-dependent and 
      independent manner.
AB  - In response to cytokine stimuli, Stats are phosphorylated and translocated to the
      nucleus to activate target genes. Then, most are dephosphorylated and returned to
      the cytoplasm. Using Ba/F3 cells, we found that the nuclear export of Stat5B by
      cytokine depletion was inhibited by leptomycin B (LMB), a specific inhibitor of
      nuclear export receptor chromosome region maintenance 1. Interestingly, LMB
      treatment in the absence of cytokine led to the accumulation of Stat5B in the
      nucleus, suggesting that Stat5B shuttles between the nucleus and the cytoplasm as
      a monomer without cytokine stimulation. This notion is supported by the
      observation that LMB-induced accumulation of Stat5B in the nucleus was also
      observed with Stat5B having a mutated tyrosine 699, which is essential for dimer
      formation. Using a series of mutant Stat5Bs, we identified a part of the coiled
      coil domain to be a critical region for monomer nuclear import and a more N
      terminal region to be critical for the cytokine stimulation dependent import of
      Stat5B. Taken together, we propose a model in which Stat5B shuttles between the
      nucleus and cytoplasm by two different mechanisms, one being a factor-independent
      constitutive shuttling by monomeric form, and the other, a factor stimulation
      dependent one regulated by tyrosine phosphorylation and subsequent dimerization.

PMID- 11971005
TI  - Recombinant carp parvalbumin, the major cross-reactive fish allergen: a tool for
      diagnosis and therapy of fish allergy.
AB  - IgE-mediated reactions to fish allergens represent one of the most frequent
      causes of food allergy. We have constructed an expression cDNA library from carp
      (Cyprinus carpio) muscle in phage lambda gt11 and used serum IgE from a fish
      allergic patient to isolate 33 cDNA clones that coded for two parvalbumin
      isoforms (Cyp c 1.01 and Cyp c 1.02) with comparable IgE binding capacities. Both
      isoforms represented calcium-binding proteins that belonged to the beta-lineage
      of parvalbumins. The Cyp c 1.01 cDNA was overexpressed in Escherichia coli, and
      rCyp c 1.01 was purified to homogeneity. Circular dichroism analysis and mass
      spectroscopy showed that rCyp c 1.01 represented a folded protein with mainly
      alpha-helical secondary structure and a molecular mass of 11,416 Da,
      respectively. rCyp c 1.01 reacted with IgE from all fish-allergic patients tested
      (n = 60), induced specific and dose-dependent basophil histamine release, and
      contained most of the IgE epitopes (70%) present in natural allergen extracts
      from cod, tuna, and salmon. Therefore, it may be used to identify patients
      suffering from IgE-mediated fish allergy. The therapeutic potential of rCyp c
      1.01 is indicated by our findings that rabbit Abs raised against rCyp c 1.01
      inhibited the binding of IgE (n = 25) in fish-allergic patients to rCyp c 1.01
      between 35 and 97% (84% mean inhibition) and that depletion of calcium strongly
      reduced IgE recognition of rCyp c 1.01. The latter results suggest that it will
      be possible to develop strategies for immunotherapy for fish allergy that are
      based on calcium-free hypoallergenic rCyp c 1.01 derivatives.

PMID- 11971006
TI  - Identification of the streptococcal M protein binding site on membrane cofactor
      protein (CD46).
AB  - Adherence of group A streptococcus (GAS) to keratinocytes is mediated by an
      interaction between human CD46 (membrane cofactor protein) with streptococcal
      cell surface M protein. CD46 belongs to a family of proteins that contain
      structurally related short consensus repeat (SCR) domains and regulate the
      activation of the complement components C3b and/or C4b. CD46 possesses four SCR
      domains and the aim of this study was to characterize their interaction with M
      protein. Following confirmation of the M6 protein-dependent interaction between
      GAS and human keratinocytes, we demonstrated that M6 protein binds soluble
      recombinant CD46 protein and to a CD46 construct containing only SCRs 3 and 4. M6
      protein did not bind to soluble recombinant CD46 chimeric proteins that had the
      third and/or fourth SCR domains replaced with the corresponding domains from
      another complement regulator, CD55 (decay-accelerating factor). Homology-based
      molecular modeling of CD46 SCRs 3 and 4 revealed a cluster of positively charged
      residues between the interface of these SCR domains similar to the verified M
      protein binding sites on the plasma complement regulators factor H and C4b
      binding protein. The presence of excess M6 protein did not inhibit the cofactor
      activity of CD46 and the presence of excess C3b did not inhibit the ability of
      CD46 to bind M6 protein by ELISA. In conclusion, 1) adherence of M6 GAS to
      keratinocytes is M protein dependent and 2) a major M protein binding site is
      located within SCRs 3 and 4, probably at the interface of these two domains, at a
      site distinct from the C3b-binding and cofactor site of CD46.

PMID- 11971007
TI  - Dual role for nitric oxide in paracoccidioidomycosis: essential for resistance,
      but overproduction associated with susceptibility.
AB  - Using a murine model of susceptibility and resistance to paracoccidioidomycosis,
      we have previously demonstrated that immunosuppression occurs in susceptible
      (B10.A), but not in resistant (A/Sn), mouse strains. Accumulating evidence shows
      that NO is involved in the induction of T cell immunosuppression during infection
      as well as in the killing of Paracoccidioides brasiliensis. In the present work,
      we focused on NO and other macrophage products that could be associated with
      resistance or susceptibility to paracoccidioidomycosis. A striking difference was
      related to NO and TNF production. Macrophages from B10.A mice produced high and
      persistent NO levels, while in A/Sn animals, TNF production predominated. In in
      vitro cultures, P. brasiliensis-infected macrophages from A/Sn mice also produced
      large amounts of TNF, while B10.A macrophages only produced NO. TNF production by
      B10.A macrophages appeared to be suppressed by NO, because the addition of
      aminoguanidine sulfate, an inducible NO synthase (NOS2) inhibitor, resulted in
      TNF production. These results suggested that enhanced TNF or NO production is
      associated with resistance and susceptibility, respectively. However, regardless
      of the mouse strain, NOS2-deficient or aminoguanidine sulfate-treated mice
      presented extensive tissue lesions with increased fungal load in lungs and liver
      compared with their controls. We conclude that NOS2-derived NO is essential for
      resistance to paracoccidioidomycosis, but overproduction is associated with
      susceptibility.

PMID- 11971008
TI  - Divergence of apoptosis-inducing and preventing signals in bacteria-faced
      macrophages through myeloid differentiation factor 88 and IL-1 receptor
      associated kinase members.
AB  - The induction of apoptosis in host cells is a common strategy by which pathogenic
      bacteria interfere with the host immune response. The Yersinia enterocolitica
      outer protein P (YopP) inhibits activation of transcription factor NF-kappa B in
      macrophages, which suppresses NF-kappa B-dependent antiapoptotic activities. The
      simultaneous initiation of proapoptotic signaling by yersiniae infection or LPS
      treatment results in macrophage apoptosis. In this study, we used YopP as a tool
      to dissect survival- and death-inducing pathways in bacteria-faced macrophages.
      We cotransfected J774A.1 macrophages with expression plasmids for YopP and
      dominant-negative mutants of signal transmitters of the NF-kappa B cascade
      downstream from the LPS receptor complex. Dominant-negative myeloid
      differentiation factor 88 (MyD88) or IL-1R-associated kinase (IRAK) 2 diminished
      LPS-induced apoptosis in YopP-transfected macrophages, suggesting implication of
      MyD88 and IRAK2 in signaling cell death. In contrast, dominant-negative IRAK1 and
      TNFR-associated factor 6 (TRAF6) did not provide protection, but augmented LPS
      mediated apoptosis in the absence of YopP, which indicates roles of IRAK1 and
      TRAF6 in the antiapoptotic signal relay of the NF-kappa B cascade. The distinct
      functions of IRAK members in macrophage survival were reflected by opposing
      effects of dominant-negative IRAK1 and IRAK2 on Y. enterocolitica-mediated
      apoptosis. Yersiniae- and LPS-dependent cell death were substantially attenuated
      by a specific caspase-8 inhibitory peptide or by dominant negative Fas-associated
      death domain protein (FADD). This suggests, that Yersinia-induced apoptosis
      involves a proapoptotic signal relay through MyD88 and IRAK2, which potentially
      targets the Fas-associated death domain protein/caspase-8 apoptotic pathway,
      whereas IRAK1 and TRAF6 counteract the bacteria-induced cytotoxic response by
      signaling macrophage survival.

PMID- 11971009
TI  - Enlargement of secretory vesicles by protein tyrosine phosphatase PTP-MEG2 in rat
      basophilic leukemia mast cells and Jurkat T cells.
AB  - Stimulus-induced secretion of bioactive polypeptides is a fundamental aspect of
      the immune system. Secretory proteins are synthesized in the endoplasmic
      reticulum and are transported through the Golgi apparatus to the trans-Golgi
      network, where they are sorted into transport vesicles that bud off and fuse into
      condensing vacuoles, which subsequently undergo an editing and concentration
      process to become mature secretory vesicles. In this study, we report that the
      PTP-MEG2 protein tyrosine phosphatase is located on these vesicles in mast cells.
      Expression of PTP-MEG2 caused a striking enlargement of these vesicles in both
      rat basophilic leukemia mast cells and Jurkat T leukemia cells into giant
      vesicles with diameters of up to several micrometers. The fused vesicles did not
      acquire markers for other compartments and were adjacent to the trans-Golgi
      network, contained carboxypeptidase E, chromogranin C, and IL-2, and had an
      electron-dense core typical of secretory vesicles. Expression of PTP-MEG2 also
      caused a reduction in the secretion of IL-2 from stimulated Jurkat cells. The
      effects of PTP-MEG2 on secretory vesicles required the catalytic activity of PTP
      MEG2 and was rapidly reversed by pervanadate. We propose that PTP-MEG2 represents
      a novel connection between tyrosine dephosphorylation and the regulation of
      secretory vesicles in hematopoietic cells.

PMID- 11971010
TI  - TNF regulates chemokine induction essential for cell recruitment, granuloma
      formation, and clearance of mycobacterial infection.
AB  - Host immunity to mycobacterial infection is dependent on the activation of T
      lymphocytes and their recruitment with monocytes to form granulomas. These
      discrete foci of activated macrophages and lymphocytes provide a microenvironment
      for containing the infection. The cytokine, TNF, is essential for the formation
      and maintenance of granulomas, but the mechanisms by which TNF regulates these
      processes are unclear. We have compared the responses of TNF-deficient (TNF(-/-))
      and wild-type C57BL/6 mice to infection with Mycobacterium smegmatis, a potent
      inducer of TNF, and virulent Mycobacterium tuberculosis to delineate the TNF
      dependent and -independent components of the process. The initial clearance of M.
      smegmatis was TNF independent, but TNF was required for the early expression of
      mRNA encoding C-C and C-X-C chemokines and the initial recruitment of CD11b(+)
      macrophages and CD4(+) T cells to the liver during the second week of infection.
      Late chemokine expression and cell recruitment developed in TNF(-/-) mice
      associated with enhanced Th1-like T cell responses and mycobacterial clearance,
      but recruited leukocytes did not form tight granulomas. Infection of TNF(-/-)
      mice with M. tuberculosis also resulted in an initial delay in chemokine
      induction and cellular recruitment to the liver. Subsequently, increased mRNA
      expression was evident in TNF(-/-) mice, but the loosely associated lymphocytes
      and macrophages failed to form granulomas and prevent progressive infection.
      Therefore, TNF orchestrates early induction of chemokines and initial leukocyte
      recruitment, but has an additional role in the aggregation of leukocytes into
      functional granulomas capable of controlling virulent mycobacterial infection.

PMID- 11971011
TI  - Rapid IL-4 production by Leishmania homolog of mammalian RACK1-reactive CD4(+) T
      cells in resistant mice treated once with anti-IL-12 or -IFN-gamma antibodies at
      the onset of infection with Leishmania major instructs Th2 cell development,
      resulting in nonhealing lesions.
AB  - Rapid production of IL-4 by Leishmania homolog of mammalian RACK1 (LACK)-reactive
      CD4(+) T cells expressing the V beta 4-V alpha 8 TCR chains has been shown to
      drive aberrant Th2 cell development and susceptibility to Leishmania major in
      BALB/c mice. In contrast, mice from resistant strains fail to express this early
      IL-4 response. However, administration of either anti-IL-12 or -IFN-gamma at the
      initiation of infection allows the expression of this early IL-4 response in
      resistant mice. In this work we show that Leishmania homolog of mammalian RACK1
      reactive CD4(+) T cells also expressing the V beta 4-V alpha 8 TCR chains are the
      source of the early IL-4 response to L. major in resistant mice given anti-IL-12
      or -IFN-gamma Abs only at the onset of infection. Strikingly, these cells were
      found to be required for the reversal of the natural resistance of C57BL/6 mice
      following a single administration of anti-IL-12 or -IFN-gamma Abs. Together these
      results suggest that a deficiency in mechanisms capable of down-regulating the
      early IL-4 response to L. major contributes to the exquisite susceptibility of
      BALB/c mice to L. major.

PMID- 11971012
TI  - Mycobacterium tuberculosis induces differential cytokine production from
      dendritic cells and macrophages with divergent effects on naive T cell
      polarization.
AB  - Th1-mediated cellular responses are important for protection in tuberculosis.
      However, the mechanisms and APC types responsible for initiating Th1 responses
      are not well understood. These studies show that macrophages and dendritic cells,
      albeit both being APC, respond differently following Mycobacterium tuberculosis
      infection and thereby have different consequences for the development of naive T
      cells. We report that M. tuberculosis-infected dendritic cells bias the
      polarization of OVA peptide-specific naive transgenic T cells to the Th1
      phenotype, and, in contrast, in the presence of infected macrophages naive T
      cells do not develop a Th1 phenotype. Comparison of the cytokine profile
      expressed by the infected dendritic cells and macrophages revealed several
      differences, the most striking being that infected macrophages did not express
      the Th1-promoting cytokine IL-12. These studies also show that IL-10 is
      responsible for the failure of IL-12 production by M. tuberculosis-infected
      macrophages, and that the effects of IL-10 can be overcome by IFN-gamma priming.
      We speculate that the observed difference in response of the two APC types to M.
      tuberculosis infection may be a reflection of their respective roles in immune
      initiation and granuloma regulation.

PMID- 11971013
TI  - Impaired Th2 development and increased mortality during Schistosoma mansoni
      infection in the absence of CD40/CD154 interaction.
AB  - The role of CD40/CD154 interaction during infection has primarily focused on
      pathogens that drive inflammatory Th1 responses. In this study, we show that
      CD40/CD154 interaction is a fundamental requirement for Th2 response development
      to the parasitic helminth Schistosoma mansoni. Compared with infected wild-type
      mice, greatly reduced levels of Th2-associated cytokines were measured both in
      vitro and in vivo, and no IgE or IgG1 was detected in infected CD154(-/-) mice.
      In the absence of an overt Th2 response, no exaggerated Th1 response was mounted
      by CD154(-/-) mice. Infected CD154(-/-) mice suffered severe morbidity and
      mortality, even though parasitemias in wild-type and CD154(-/-) mice did not
      differ significantly. These data indicate that CD40/CD154 interaction is required
      to allow development of a Th2-dominated immune response to S. mansoni and support
      the view that failure to develop such a response can have fatal consequences.

PMID- 11971014
TI  - Profound differences in leukocyte-endothelial cell responses to
      lipopolysaccharide versus lipoteichoic acid.
AB  - We have investigated the effects of LPS from Escherichia coli, lipoteichoic acid
      (LTA), and peptidoglycan (PepG) from Staphylococcus aureus, and live S. aureus on
      leukocyte-endothelial interactions in vivo using intravital microscopy to
      visualize muscle microvasculature. Systemic vs local administration of LPS
      induced very different responses. Local administration of LPS into muscle induced
      significant leukocyte rolling, adhesion, and emigration in postcapillary venules
      at the site of injection. LPS given systemically dramatically dropped circulating
      leukocyte counts and increased neutrophils in the lung. However, the drop in
      circulating leukocytes was not associated with leukocyte sequestration to the
      site of injection (peritoneum) nor to peripheral microvessels in muscles. Unlike
      LPS, various preparations of LTA had no systemic and very minor local effect on
      leukocyte-endothelial interactions, even at high doses and for prolonged
      duration. LPS, but not LTA, potently activated human endothelium to recruit
      leukocytes under flow conditions in vitro. Endothelial adhesion molecule
      expression was also increased extensively with LPS, but not LTA. Interestingly,
      systemic administration of live S. aureus induced leukocyte-endothelial cell
      responses similar to LPS. PepG was able to induce leukocyte-endothelial
      interactions in muscle and peritoneum, but had no effect systemically (no
      increase in neutrophils in lungs and no decrease in circulating neutrophil
      counts). These results demonstrate that: 1) LPS has potent, but divergent local
      and systemic effects on leukocyte-endothelial interactions; 2) S. aureus can
      induce a systemic response similar to LPS, but this response is unlikely to be
      due to LTA, but more likely to be mediated in part by PepG.

PMID- 11971015
TI  - Differential roles of CC chemokine ligand 2/monocyte chemotactic protein-1 and
      CCR2 in the development of T1 immunity.
AB  - CCR2 and its major ligand, chemokine ligand 2 (CCL2)/monocyte chemotactic protein
      1, have been found to influence T1/T2 immune response polarization. Our objective
      was to directly compare the roles of CCR2 and CCL2 in T1/T2 immune response
      polarization using a model of pulmonary Cryptococcus neoformans infection. Either
      deletion of CCR2 or treatment of wild-type mice with CCL2 neutralizing Ab
      produced significant and comparable reductions in macrophage and T cell
      recruitment into the lungs following infection. Both CCL2 neutralization and CCR2
      deficiency resulted in significantly diminished IFN-gamma production, and
      increased IL-4 and IL-5 production by lung leukocytes (T1 to T2 switch), but only
      CCR2 deficiency promoted pulmonary eotaxin production and eosinophilia. In the
      lung-associated lymph nodes (LALN), CCL2-neutralized mice developed Ag-specific
      IFN-gamma-producing cells, while CCR2 knockout mice did not. LALN from CCR2
      knockout mice also had fewer MHCII(+)CD11c(+) and MHCII(+)CD11b(+) cells, and
      produced significantly less IL-12p70 and TNF-alpha when stimulated with heat
      killed yeast than LALN from wild-type or CCL2-neutralized mice, consistent with a
      defect in APC trafficking in CCR2 knockout mice. Neutralization of CCL2 in CCR2
      knockout mice did not alter immune response development, demonstrating that the
      high levels of CCL2 in these mice did not play a role in T2 polarization.
      Therefore, CCR2 (but not CCL2) is required for afferent T1 development in the
      lymph nodes. In the absence of CCL2, T1 cells polarize in the LALN, but do not
      traffic from the lymph nodes to the lungs, resulting in a pulmonary T2 response.

PMID- 11971016
TI  - Mitogen-activated protein kinase-activated protein kinase 2-deficient mice show
      increased susceptibility to Listeria monocytogenes infection.
AB  - Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is one of
      several kinases activated through direct phosphorylation by p38 mitogen-activated
      protein kinase. MK2 regulates LPS-induced TNF mRNA translation, and targeted
      mutation of the MK2 gene renders mice more resistant to D-galactosamine plus LPS
      induced liver damage. In the present study, we investigated the role of MK2 in
      immune defense against Listeria monocytogenes infection. MK2-deficient mice
      displayed diminished resistance to L. monocytogenes due to impaired control of
      bacterial growth. The increase in bacterial load in MK2(-/-) mice was associated
      with normal levels of IL-1 beta, IL-6, and IFN-gamma, whereas TNF production was
      strongly attenuated. In line, MK2-deficient bone marrow-derived macrophages
      showed impaired release of TNF, but not of IL-1 beta, in response to various
      bacterial stimuli in addition to decreased phagocytosis of fluorescence-labeled
      bacteria. Furthermore, spleen cells from MK2(-/-) mice displayed diminished IFN
      gamma synthesis after stimulation with L. monocytogenes. In contrast, MK2
      deficiency had no effect on macrophage generation of NO or on oxidative burst
      activity in response to L. moocytogenes. These results indicate an essential role
      of MK2 in host defense against intracellular bacteria probably via regulation of
      TNF and IFN-gamma production required for activation of antibacterial effector
      mechanisms.

PMID- 11971018
TI  - The adapter molecule Gab2 regulates Fc epsilon RI-mediated signal transduction in
      mast cells.
AB  - The recently cloned scaffolding molecule Gab2 can assemble multiple molecules
      involved in signaling pathways. Bone marrow-derived mast cells isolated from
      Gab2(-/-) mice have defective signaling probably due to the lack of the
      activation of phosphatidylinositol-3 kinase (PI3-kinase). In this study, we
      investigated the role of Gab2 using the rat basophilic leukemia 2H3 cell line
      mast cells. Fc epsilon RI aggregation induced the tyrosine phosphorylation of
      Gab2 and translocation of a significant fraction of it from the cytosol to the
      plasma membrane. As in other cells, Gab2 was found to associate with several
      signaling molecules including Src homology 2-containing protein tyrosine
      phosphatase 2, Grb2, Lyn, and phospholipase C gamma (PLC gamma). The association
      of Gab2 with Lyn and PLC gamma were enhanced after receptor aggregation.
      Overexpression of Gab2 in rat basophilic leukemia 2H3 cell line cells inhibited
      the Fc epsilon RI-induced tyrosine phosphorylation of the subunits of the
      receptor, and the phosphorylation and/or activation of Syk and mitogen-activated
      protein kinase. Downstream events such as calcium mobilization, degranulation,
      and induction of TNF-alpha and IL-6 gene transcripts were decreased in Gab2
      overexpressing cells, although Akt phosphorylation as a measure of PI3-kinase
      activation was unaffected. These results suggest that in addition to the positive
      effects mediated by PI3-kinase that are apparent in Gab2(-/-) mast cells, Gab2 by
      interacting with Lyn and PLC gamma may have negative regulatory effects on Fc
      epsilon RI-induced mast cell signaling and functions.

PMID- 11971017
TI  - The role of IL-18 in blood-stage immunity against murine malaria Plasmodium
      yoelii 265 and Plasmodium berghei ANKA.
AB  - A possible protective role of IL-18 in host defense against blood-stage murine
      malarial infection was studied in BALB/c mice using a nonlethal strain,
      Plasmodium yoelii 265, and a lethal strain, Plasmodium berghei ANKA. Infection
      induced an increase in mRNA expression of IL-18, IL-12p40, IFN-gamma, and TNF
      alpha in the case of P. yoelii 265 and an increase of IL-18, IL-12p40, and IFN
      gamma in the case of P. berghei ANKA. The timing of mRNA expression of IL-18 in
      both cases was consistent with a role in the induction of IFN-gamma protein
      expression. Histological examination of spleen and liver tissues from infected
      controls treated with PBS showed poor cellular inflammatory reaction, massive
      necrosis, a large number of infected parasitized RBCs, and severe deposition of
      hemozoin pigment. In contrast, IL-18-treated infected mice showed massive
      infiltration of inflammatory cells consisting of mononuclear cells and Kupffer
      cells, decreased necrosis, and decreased deposition of the pigment hemozoin.
      Treatment with rIL-18 increased serum IFN-gamma levels in mice infected with both
      parasites, delayed onset of parasitemia, conferred a protective effect, and thus
      increased survival rate of infected mice. Administration of neutralizing anti-IL
      18 Ab exacerbated infection, impaired host resistance and shortened the mean
      survival of mice infected with P. berghei ANKA. Furthermore, IL-18 knockout mice
      were more susceptible to P. berghei ANKA than were wild-type C57BL/6 mice. These
      data suggest that IL-18 plays a protective role in host defense by enhancing IFN
      gamma production during blood-stage infection by murine malaria.

PMID- 11971019
TI  - Helicobacter pylori induces macrophage apoptosis by activation of arginase II.
AB  - Helicobacter pylori infection induces innate immune responses in macrophages,
      contributing to mucosal inflammation and damage. Macrophage apoptosis is
      important in the pathogenesis of mucosal infections but has not been studied with
      H. pylori. NO derived from inducible NO synthase (iNOS) can activate macrophage
      apoptosis. Arginase competes with iNOS by converting L-arginine to L-ornithine.
      Since we reported that H. pylori induces iNOS in macrophages, we now determined
      whether this bacterium induces arginase and the effect of this activation on
      apoptosis. NF-kappa B-dependent induction of arginase II, but not arginase I, was
      observed in RAW 264.7 macrophages cocultured with H. pylori. The time course of
      apoptosis matched those of both arginase and iNOS activities. Surprisingly,
      apoptosis was blocked by the arginase inhibitors N(omega)-hydroxy-L-arginine or
      N(omega)-hydroxy-nor-L-arginine, but not by the iNOS inhibitor N-iminoethyl-L
      lysine. These findings were confirmed in peritoneal macrophages from iNOS
      deficient mice and were not dependent on bacterial-macrophage contact. Ornithine
      decarboxylase (ODC), which metabolizes L-ornithine to polyamines, was also
      induced in H. pylori-stimulated macrophages. Apoptosis was abolished by
      inhibition of ODC and was restored by the polyamines spermidine and spermine. We
      also demonstrate that arginase II expression is up-regulated in both murine and
      human H. pylori gastritis tissues, indicating the likely in vivo relevance of our
      findings. Therefore, we describe arginase- and ODC-dependent macrophage
      apoptosis, which implicates polyamines in the pathophysiology of H. pylori
      infection.

PMID- 11971020
TI  - Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: a
      critical role for monocytes in leukocyte lipopolysaccharide responses.
AB  - Leukocyte responsiveness to LPS is dependent upon CD14 and receptors of the Toll
      like receptor (TLR) family. Neutrophils respond to LPS, but conflicting data
      exist regarding LPS responses of eosinophils and basophils, and expression of
      TLRs at the protein level in these granulocyte lineages has not been fully
      described. We examined the expression of TLR2, TLR4, and CD14 and found that
      monocytes expressed relatively high levels of cell surface TLR2, TLR4, and CD14,
      while neutrophils also expressed all three molecules, but at low levels. In
      contrast, basophils expressed TLR2 and TLR4 but not CD14, while eosinophils
      expressed none of these proteins. Tested in a range of functional assays
      including L-selectin shedding, CD11b up-regulation, IL-8 mRNA generation, and
      cell survival, neutrophils responded to LPS, but eosinophils and basophils did
      not. In contrast to previous data, we found, using monocyte depletion by negative
      magnetic selection, that neutrophil responses to LPS were heavily dependent upon
      the presence of a very low level of monocytes, and neutrophil survival induced by
      LPS at 22 h was monocyte dependent. We conclude that LPS has little role in the
      regulation of peripheral blood eosinophil and basophil function, and that, even
      in neutrophils, monocytes orchestrate many previously observed leukocyte LPS
      response patterns.

PMID- 11971021
TI  - Role of mitogen-activated protein kinases in CpG DNA-mediated IL-10 and IL-12
      production: central role of extracellular signal-regulated kinase in the negative
      feedback loop of the CpG DNA-mediated Th1 response.
AB  - The mitogen-activated protein kinases, extracellular signal-regulated kinase
      (ERK), and p38, are activated in response to infectious agents and innate immune
      stimulators such as CpG DNA, and regulate the subsequent initiation and
      termination of immune responses. CpG DNA activates p38 and ERK with slightly
      different kinetics in monocytic cells. The present studies investigated the roles
      of these two key mitogen-activated protein kinases in regulating the CpG DNA
      induced production of pro- and anti-inflammatory cytokines in the macrophage-like
      cell line RAW264.7. p38 activity was essential for the induction of both IL-10
      and IL-12 expression by CpG DNA. In contrast, CpG DNA-mediated ERK activation was
      shown to suppress IL-12 production, but to be essential for the CpG DNA-induced
      IL-10 production. Studies using rIL-10 and IL-10 gene-deficient mice demonstrated
      that the inhibitory effect of ERK on CpG DNA-mediated IL-12 production is
      indirect, due to the role of ERK in mediating IL-10 production. These results
      demonstrate that ERK and p38 differentially regulate the production of pro- and
      anti-inflammatory cytokines in APCs that have been activated by CpG DNA. CpG DNA
      induced p38 activity is required for the resulting innate immune activation. In
      contrast, ERK plays a central negative regulatory role in the CpG DNA-mediated
      Th1 type response by promoting production of the Th2 type cytokine, IL-10.

PMID- 11971022
TI  - Endotoxin-stimulated nitric oxide production inhibits expression of cytochrome c
      oxidase in ANA-1 murine macrophages.
AB  - In endotoxin (LPS)-mediated states of sepsis, inducible NO synthase expression
      and NO production are associated with molecular regulatory functions that
      determine the host inflammatory response. NO inhibits cellular respiration and
      mitochondrial electron transport by inhibition of cytochrome c oxidase (CcO)
      activity. CcO is the terminal complex of the mitochondrial respiratory chain,
      responsible for 90% of cellular oxygen consumption and essential for cellular
      energy production. Subunit 1 (CcO I) is considered to be the most critical of the
      13 CcO component subunits. In this regard little is known of the effect of NO on
      the transcriptional program for CcO expression. In ANA-1 murine macrophages, LPS
      mediated NO synthesis decreases CcO enzyme activity, CcO I protein expression,
      and CcO I steady mRNA levels. Mitochondrial run-on analysis demonstrates
      unaltered CcO I mitochondrial gene transcription. Half-life analysis indicates
      that CcO I mRNA stability is significantly decreased in the presence of LPS
      mediated NO synthesis. In this study using LPS-stimulated ANA-1 murine
      macrophages, we demonstrate that expression of the mitochondrial gene product,
      CcO I, is significantly decreased as the result of a unique and previously
      uncharacterized, NO-dependent post-transcriptional regulatory mechanism.

PMID- 11971023
TI  - Leukocyte-endothelial cell interactions are enhanced in dermal postcapillary
      venules of MRL/fas(lpr) (lupus-prone) mice: roles of P- and E-selectin.
AB  - MRL/fas(lpr) mice are affected by a systemic autoimmune disease that results in
      widespread leukocytic infiltration of the vasculature, including in the skin. The
      molecular pathways responsible for this leukocyte recruitment are poorly
      understood. Therefore, the aim of these experiments was to examine the mechanisms
      of leukocyte trafficking in the dermal microvasculature of MRL/fas(lpr) mice.
      Intravital microscopy was used to examine leukocyte rolling and adhesion in
      dermal postcapillary venules of MRL/fas(lpr) mice at 8, 12, and 16 wk of age.
      When compared with age-matched BALB/c and MRL(+/+) (nondiseased) mice, leukocyte
      rolling and adhesion in MRL/fas(lpr) mice were significantly enhanced at 12 wk of
      age, and remained elevated at 16 wk of age. At 8 and 12 wk, leukocyte rolling in
      all three strains was almost entirely inhibited by an anti-P-selectin mAb. In
      contrast, at 16 wk some (approximately 10%) leukocyte rolling persisted following
      P-selectin blockade. This residual rolling was predominantly inhibitable with an
      anti-E-selectin mAb; however, treatment with anti-E-selectin mAb alone had a
      minimal effect. P-selectin-deficient MRL/fas(lpr) mice also displayed leukocyte
      rolling that was significantly lower than in wild-type MRL/fas(lpr) mice.
      However, in these mice, leukocyte adhesion remained at the elevated levels
      observed in wild-type MRL/fas(lpr) mice. This adhesion was eliminated by chronic
      treatment with anti-E-selectin mAb. These findings indicate that leukocyte
      endothelial cell interactions are enhanced in the dermal microvasculature of
      MRL/fas(lpr) mice above the age of 12 wk. Furthermore, the data suggest that the
      endothelial selectins share overlapping roles in mediating this enhanced
      leukocyte recruitment.

PMID- 11971024
TI  - SHIP negatively regulates IgE + antigen-induced IL-6 production in mast cells by
      inhibiting NF-kappa B activity.
AB  - We demonstrate in this study that IgE + Ag-induced proinflammatory cytokine
      production is substantially higher in Src homology-2-containing inositol 5'
      phosphatase (SHIP)(-/-) than in SHIP(+/+) bone marrow-derived mast cells (BMMCs).
      Focusing on IL-6, we found that the repression of IL-6 mRNA and protein
      production in SHIP(+/+) BMMCs requires the enzymatic activity of SHIP, because
      SHIP(-/-) BMMCs expressing wild-type, but not phosphatase-deficient (D675G), SHIP
      revert the IgE + Ag-induced increase in IL-6 mRNA and protein down to levels seen
      in SHIP(+/+) BMMCs. Comparing the activation of various signaling pathways to
      determine which ones might be responsible for the elevated IL-6 production in
      SHIP(-/-) BMMCs, we found the phosphatidylinositol 3-kinase/protein kinase B
      (PKB), extracellular signal-related kinase (Erk), p38, c-Jun N-terminal kinase,
      and protein kinase C (PKC) pathways are all elevated in IgE + Ag-induced SHIP(-/
      ) cells. Moreover, inhibitor studies suggested that all these pathways play an
      essential role in IL-6 production. Looking downstream, we found that IgE + Ag
      induced IL-6 production is dependent on the activity of NF-kappa B and that I
      kappa B phosphorylation/degradation and NF-kappa B translocation, DNA binding and
      transactivation are much higher in SHIP(-/-) BMMCs. Interestingly, using various
      pathway inhibitors, it appears that the phosphatidylinositol 3-kinase/PKB and PKC
      pathways elevate IL-6 mRNA synthesis, at least in part, by enhancing the
      phosphorylation of I kappa B and NF-kappa B DNA binding while the Erk and p38
      pathways enhance IL-6 mRNA synthesis by increasing the transactivation potential
      of NF-kappa B. Taken together, our data are consistent with a model in which SHIP
      negatively regulates NF-kappa B activity and IL-6 synthesis by reducing IgE + Ag
      induced phosphatidylinositol-3,4,5-trisphosphate levels and thus PKB, PKC, Erk,
      and p38 activation.

PMID- 11971025
TI  - Selective inhibition of cyclooxygenase-2 expression by 15-deoxy
      Delta(12,14)(12,14)-prostaglandin J(2) in activated human astrocytes, but not in
      human brain macrophages.
AB  - Overexpression of the inducible cyclooxygenase (COX-2) and inducible NO synthase
      (iNOS) in activated brain macrophages (microglia) and astrocytes appears central
      to many neuroinflammatory conditions. 15-Deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2))
      is a ligand for the peroxisome proliferator-activated receptor (PPAR)gamma. It
      has been proposed as an inhibitor of microglial activation, based on the study of
      iNOS down-regulation in rodent microglia. Because iNOS induction after cytokine
      activation remains controversial in human microglia, we examined the effect of
      15d-PGJ(2) and other PPAR agonists on human microglia and astrocytes, using COX-2
      induction as an index of activation. We found that PPAR alpha ligands (clofibrate
      and WY14643) enhanced IL-1 beta-induced COX-2 expression in human astrocytes and
      microglia, while inhibiting IL-1 beta plus IFN-gamma induction of iNOS in
      astrocytes. This is the first description of an inhibition of iNOS uncoupled from
      that of COX-2. 15d-PGJ(2) suppressed COX-2 induction in human astrocytes. It
      prevented NF-kappa B binding to the COX-2 promoter through a new pathway that is
      the repression of NF-kappa Bp50 induction by IL-1 beta. In contrast, 15d-PGJ(2)
      increased c-Jun and c-Fos DNA-binding activity in astrocytes, which may result in
      the activation of other inflammatory pathways. In human microglia, no effect of
      15d-PGJ(2) on COX-2 and NF-kappa Bp65/p50 induction was observed. However, the
      entry of 15d-PGJ(2) occurred in microglia because STAT-1 and c-Jun expression was
      modulated. Our data suggest the existence of novel pathways mediated by 15d
      PGJ(2) in human astrocytes. They also demonstrate that, unlike astrocytes and
      peripheral macrophages or rodent brain macrophages, human microglia are not
      subject to the anti-inflammatory effect of 15d-PGJ(2) in terms of COX-2
      inhibition.

PMID- 11971026
TI  - IL-16 promotes leukotriene C(4) and IL-4 release from human eosinophils via CD4-
      and autocrine CCR3-chemokine-mediated signaling.
AB  - Human eosinophils are potential sources of inflammatory and immunomodulatory
      mediators, including cysteinyl leukotrienes, chemokines, and cytokines, which are
      pertinent to allergic inflammation. We evaluated the means by which IL-16, a
      recognized eosinophil chemoattractant, might act on eosinophils to affect their
      capacity to release leukotriene C(4) (LTC(4)) or their preformed stores of
      chemokines (eotaxin, RANTES) or Th1 (IL-12) or Th2 (IL-4) cytokines. IL-16 dose
      dependently (0.01-100 nM) elicited new lipid body formation, intracellular LTC(4)
      formation at lipid bodies, and priming for enhanced calcium ionophore-activated
      LTC(4) release. IL-16 also elicited brefeldin A-inhibitable, vesicular transport
      mediated release of preformed IL-4, but not IL-12, from eosinophils. CD4 is a
      recognized IL-16R, and accordingly anti-CD4 Fab, soluble CD4, and a CD4 domain 4
      based IL-16 blocking peptide inhibited the actions of IL-16 on eosinophils.
      Although CD4 is not G-protein coupled, pertussis toxin inhibited IL-16-induced
      eosinophil activation. IL-16 actions were found to be mediated by the autocrine
      activity, not of platelet-activating factor, but rather of endogenous CCR3-acting
      chemokines. IL-16 induced the rapid vesicular transport-mediated release of
      RANTES. The effects of IL-16 were blocked by CCR3 inhibitors (met-RANTES, anti
      CCR3 mAb) and by neutralizing anti-eotaxin and anti-RANTES mAbs, but not by
      platelet-activating factor receptor antagonists (CV6209, BN52021). RANTES and
      eotaxin each enhanced LTC(4) and IL-4 (but not IL-12) release. Therefore, IL-16
      activation of eosinophils is CD4-mediated to elicit the extracellular release of
      preformed RANTES and eotaxin, which then in an autocrine fashion act on plasma
      membrane CCR3 receptors to stimulate both enhanced LTC(4) production and the
      preferential release of IL-4, but not IL-12, from within eosinophils.

PMID- 11971027
TI  - IFN-gamma, but not Fas, mediates reduction of allergen-induced mucous cell
      metaplasia by inducing apoptosis.
AB  - Inflammatory responses induced by allergen exposure cause mucous cell metaplasia
      (MCM) by differentiation of existing and proliferating epithelial cells into
      mucus-storing cells. Airway epithelia have various mechanisms that resolve these
      changes to form normal airway epithelia. In this report, we first investigated
      the state of mucous cell metaplasia and the mechanisms by which MCM is reduced
      despite continued exposures to allergen. After 5 days of allergen exposure,
      extensive MCM had developed but was reduced when allergen challenge was continued
      for 15 days. During this exposure period, IL-13 levels decreased and IFN-gamma
      levels increased in the bronchoalveolar lavage fluid. In contrast, IL-13 levels
      decreased but IFN-gamma was not detected at any time point during the resolution
      of MCM following cessation of allergen exposure. Instillation of IFN-gamma but
      not anti-Fas caused accelerated resolution of MCM and MCM was not resolved in
      Stat1-deficient mice exposed to allergen for 15 days, confirming that IFN-gamma
      is crucial for reducing MCM during prolonged exposures to allergen. IFN-gamma but
      not anti-Fas induced apoptotic cell death in proliferating normal human bronchial
      epithelial cells and in human bronchial epithelial cells from subjects with
      asthma. The apoptotic effect of IFN-gamma was caspase dependent and was inhibited
      by IL-13, indicating that the Th2 milieu in asthmatics may maintain MCM by
      preventing cell death in metaplastic mucous cells. These studies could be useful
      in the understanding of deficiencies leading to chronicity in airway changes and
      designing novel therapies to reverse MCM and airway obstruction in asthmatics.

PMID- 11971028
TI  - A functional role of HLA-G expression in human gliomas: an alternative strategy
      of immune escape.
AB  - HLA-G is a nonclassical MHC molecule with highly limited tissue distribution that
      has been attributed chiefly immune regulatory functions. Glioblastoma is
      paradigmatic for the capability of human cancers to paralyze the immune system.
      To delineate the potential role of HLA-G in glioblastoma immunobiology,
      expression patterns and functional relevance of this MHC class Ib molecule were
      investigated in glioma cells and brain tissues. HLA-G mRNA expression was
      detected in six of 12 glioma cell lines in the absence of IFN-gamma and in 10 of
      12 cell lines in the presence of IFN-gamma. HLA-G protein was detected in four of
      12 cell lines in the absence of IFN-gamma and in eight of 12 cell lines in the
      presence of IFN-gamma. Immunohistochemical analysis of human brain tumors
      revealed expression of HLA-G in four of five tissue samples. Functional studies
      on the role of HLA-G in glioma cells were conducted with alloreactive PBMCs, NK
      cells, and T cell subpopulations. Expression of membrane-bound HLA-G1 and soluble
      HLA-G5 inhibited alloreactive and Ag-specific immune responses. Gene transfer of
      HLA-G1 or HLA-G5 into HLA-G-negative glioma cells (U87MG) rendered cells highly
      resistant to direct alloreactive lysis, inhibited the alloproliferative response,
      and prevented efficient priming of cytotoxic T cells. The inhibitory effects of
      HLA-G were directed against CD8 and CD4 T cells, but appeared to be NK cell
      independent. Interestingly, few HLA-G-positive cells within a population of HLA-G
      negative tumor cells exerted significant immune inhibitory effects. We conclude
      that the aberrant expression of HLA-G may contribute to immune escape in human
      glioblastoma.

PMID- 11971029
TI  - Dimethylfumarate inhibits TNF-induced nuclear entry of NF-kappa B/p65 in human
      endothelial cells.
AB  - Fumaric acid esters, mainly dimethylfumarate (DMF), have been successfully used
      to treat psoriasis. Based on previous observations that DMF inhibited expression
      of several TNF-induced genes in endothelial cells, we wished to explore the
      molecular basis of DMF function in greater detail. In first experiments we
      analyzed DMF effects on tissue factor expression in human endothelial cells in
      culture, because tissue factor is expressed by two independent sets of
      transcription factors, by NF-kappa B via TNF and by early gene response-1
      transcription factor via vascular endothelial growth factor (VEGF). We show that
      DMF inhibits TNF-induced tissue factor mRNA and protein expression as well as TNF
      induced DNA binding of NF-kappa B proteins, but not VEGF-induced tissue factor
      protein, mRNA expression, or VEGF-induced early gene response-1 transcription
      factor/DNA binding. To determine where DMF interferes with the TNF/NF-kappa B
      signaling cascade, we next analyzed DMF effects on I kappa B and on the
      subcellular distribution of NF-kappa B. DMF does not inhibit TNF-induced I kappa
      B alpha phosphorylation and I kappa B degradation; thus, NF-kappa B is properly
      released from I kappa B complexes even in the presence of DMF. Importantly, DMF
      inhibits the TNF-induced nuclear entry of NF-kappa B proteins, and this effect
      appears selective for NF-kappa B after the release from I kappa B, because the
      constitutive shuttling of inactive NF-kappa B/I kappa B complexes into and out
      from the nucleus is not blocked by DMF. Moreover, DMF does not block NF-kappa
      B/DNA binding. In conclusion, DMF appears to selectively prevent the nuclear
      entry of activated NF-kappa B, and this may be the basis of its beneficial effect
      in psoriasis.

PMID- 11971030
TI  - Gene transfer of Ig-fusion proteins into B cells prevents and treats autoimmune
      diseases.
AB  - Based on the tolerogenic properties of IgG carriers and B cell Ag presentation,
      we developed a retrovirally mediated gene expression approach for treatment of
      autoimmune conditions. In this study, we show that the IgG-Ag retroviral
      constructs, expressing myelin basic protein (MBP) or glutamic acid decarboxylase
      in B cells, can be used for the treatment of murine models for multiple sclerosis
      and diabetes. Transduction of syngeneic B cells with MBP-IgG leads to the
      amelioration of ongoing experimental allergic encephalomyelitis induced by the
      transfer of primed cells from PLxSJL F(1) mice with ongoing disease and could be
      effective even after symptoms appeared. This effect is specific and does not
      involve bystander suppression because treatment with MBP-IgG does not affect
      disease induced after immunization with proteolipid protein immunodominant
      peptide plus MBP. Interestingly, if donor B cells are derived from gld mice (Fas
      ligand-negative), then tolerance is not induced with a model Ag although there
      was no evidence for Fas ligand-mediated deletion of target T cells. In
      spontaneous diabetes in nonobese diabetic mice, we were able to stop the ongoing
      autoimmune process by treatment at 7-10 wk with glutamic acid decarboxylase-IgG
      retrovirally transduced B cells, or attenuate it with B cells transduced with an
      insulin B chain (B9-23) epitope IgG fusion protein. Furthermore, IgG fusion
      protein gene therapy can also protect primed recipients from Ag-induced
      anaphylactic shock, and thus does not cause immune deviation. These results
      demonstrate proof of principle for future efforts to develop this approach in a
      clinical setting.

PMID- 11971031
TI  - Persistent decreases in blood plasmacytoid dendritic cell number and function
      despite effective highly active antiretroviral therapy and increased blood
      myeloid dendritic cells in HIV-infected individuals.
AB  - Dendritic cells (DC) have an instrumental role in the activation and function of
      both innate and adaptive immune responses. In humans, at least two distinct DC
      subsets have been characterized based on phenotypic markers: the myeloid DC (MDC)
      and the plasmacytoid DC (PDC). Both subsets are critical producers of cytokines
      (IL-12 for MDC and type I/II IFNs for PDC) and are functionally different. We
      show in this study that HIV(+) individuals have a significant decrease in the
      number of the Lin(-)HLA-DR(+)CD123(+) and BDCA-2(+) PDC compared with uninfected
      donors (p = 0.0001). HIV(+) individuals also have a sustained impairment in viral
      induced IFN-alpha production (p < 0.0001). The decrease of the PDC subsets did
      not correlate with CD4 count or viral load and was not reversed in subjects under
      virally suppressive treatment, suggesting an irreversible change after infection.
      By contrast, the absolute number and median frequency of MDC in HIV-infected
      individuals were similar to those observed in uninfected controls, while a
      significant decrease was present in subjects with >5000 HIV-1 copies/ml. The
      inverse association with viral load of the MDC number, but not of IFN-alpha
      secretion or the number of PDC, suggests a role for MDC in viral control. Our
      data suggest that DC subsets are differentially reconstituted during the immune
      recovery associated with antiviral therapy. The persistent impairment of certain
      DC subsets may result in a sustained defect in DC-mediated innate immune
      functions despite an effective treatment regimen.

PMID- 11971032
TI  - A ras-mutated peptide targeted by CTL infiltrating a human melanoma lesion.
AB  - Ags derived from commonly mutated oncogenic proteins seem ideally suited as
      targets for tumor immunotherapy. Nonetheless, only a few mutated epitopes
      efficiently presented by human tumors have thus far been identified. We describe
      here an approach to identify such epitopes. This approach involves: 1)
      identifying tumors expressing a ras mutation and isolating the tumor-infiltrating
      lymphocytes (TIL); 2) transfecting COS cells to induce expression of unknown
      mutated peptides in the context of a patient's HLA class I molecules; and 3)
      screening epitope recognition by using TIL from the tumors expressing a ras
      mutation. By using this approach, there appeared to be a N-ras mutation (a
      glutamine-to-arginine exchange at residue 61 (Q61R)), detected in a melanoma
      lesion, which was recognized specifically by the autologous TIL in the HLA-A*0101
      context. The ras peptide 55-64(Q61R) was the epitope of these TIL and was
      regularly presented by Q61R-mutated HLA-A*0101(+) melanoma cell lines. This
      peptide and its wild-type homolog (55-64(wt)) bound to HLA-A*0101 with similar
      affinities. However, only the mutated peptide could induce specific CTL expansion
      from PBL. All the CTL clones specific to the mutated peptide, failed to recognize
      the wild-type sequence on both COS and melanoma cells. These data thus show that
      oncogenic protein mutations can create shared tumor-specific CTL epitopes,
      efficiently presented by tumor cells, and that screening for oncogene-transfected
      COS cell recognition by TIL (from tumors containing mutations) is a powerful
      approach for the identification of these epitopes.

PMID- 11971033
TI  - Is clinical neurology really so difficult?

PMID- 11971034
TI  - Gluten sensitivity as a neurological illness.

PMID- 11971035
TI  - White matter change and stroke risk.

PMID- 11971036
TI  - "Sick" MRI syndrome.

PMID- 11971037
TI  - Qualitative performance characteristics differentiate dementia with Lewy bodies
      and Alzheimer's disease.

PMID- 11971038
TI  - Benefits and risks of folic acid to the nervous system.
AB  - During three decades of neurological practice I have witnessed a remarkable
      change in attitudes to the benefits and risks of folic acid therapy in nervous
      system disorders. In the 1960s all that was known and taught was that folic acid
      was harmful to the nervous system, especially in precipitating or exacerbating
      the neurological complications of vitamin B12 deficiency. So deeply held was this
      view that the possibility of neuropsychological benefits from this vitamin was
      initially viewed with considerable scepticism.

PMID- 11971039
TI  - Diffusion weighted magnetic resonance imaging in the diagnosis of reversible
      ischaemic deficits of the brainstem.
AB  - OBJECTIVES: To evaluate the sensitivity of diffusion weighted magnetic resonance
      imaging (MRI) for the diagnosis of clinically suspected reversible ischaemic
      deficits of the brainstem. METHODS: A total of 158 consecutive patients
      presenting with acute signs of brainstem dysfunction were investigated using EPI
      diffusion weighted MRI within 24 hours of the onset of symptoms. High resolution
      T1 and T2 weighted imaging was performed as a follow up after a median of six
      days. RESULTS: Fourteen of the 158 patients had a complete clinical recovery
      within 24 hours (transitory ischaemic attack (TIA)), and 19 patients recovered in
      less than one week (prolonged reversible neurological deficit (RIND)). Diffusion
      weighted MRI showed acute ischaemic deficits in 39% of patients with transient
      neurological deficits. The detection rate seemed to be higher in patients with
      longer lasting symptoms, but the difference between patients with TIA (29%) and
      RIND (47%) was not significant. CONCLUSIONS: Diffusion weighted MRI is a
      sensitive indicator of acute ischaemic brainstem deficits even in patients with
      reversible neurological deficit. Early identification of patients with TIA and
      increased risk of stroke may influence acute management and improve patient
      outcome.

PMID- 11971040
TI  - Significance of white matter high intensity lesions as a predictor of stroke from
      arteriolosclerosis.
AB  - OBJECTIVES: To determine whether the extent of white matter high intensity
      lesions (WML) on magnetic resonance imaging (MRI) is an independent predictor of
      risk for stroke from arteriolosclerosis, and whether serial evaluation of WML can
      be used to identify patients who are at risk of strokes. METHODS: Prospective
      follow up with serial MRI scans was done in 89 patients who were either diagnosed
      as having symptomatic lacunar infarcts or were stroke-free, neurologically normal
      individuals with headache or dizziness. None had significant stenosis of major
      cerebral arteries or atrial fibrillation. Multivariable analysis with the Cox
      proportional hazards model was used to test the predictive value for subsequent
      stroke of risk factor status at entry and during follow up, lacunar infarction,
      and the extent of WML (scored from 0 to 16) on the baseline scans. RESULTS:
      During follow up (mean (SD), 51 (19) months), seven strokes occurred (five
      lacunar infarcts and two haemorrhages): four in nine patients with severe WML
      (score 9-16), and three in 40 patients with mild WML (score 1-8) (log-rank test;
      p < 0.005). None of 40 patients without WML experienced stroke. The extent of WML
      was an independent predictor of subsequent stroke (relative risk for a 1 point
      score increase, 1.60; 95% confidence interval, 1.02 to 2.54; p < 0.05). In three
      strokes among 80 patients without severe WML, two occurred in four patients with
      an increase in WML score during follow up, and one occurred in the other 76
      patients without an increased score (p < 0.0001). CONCLUSIONS: Severe WML at
      baseline is an independent predictor of risk for stroke from arteriolosclerosis,
      while progression of WML during follow up may be associated with subsequent
      stroke in patients with initially mild WML.

PMID- 11971041
TI  - Continuous monitoring of cerebrovascular autoregulation: a validation study.
AB  - BACKGROUND: Continuous monitoring of dynamic cerebral autoregulation, using a
      moving correlation index of cerebral perfusion pressure and mean middle cerebral
      artery flow velocity, may be useful in patients with severe traumatic brain
      injury to guide treatment, and has been shown to be of prognostic value.
      OBJECTIVE: To compare an index of dynamic cerebral autoregulation (Mx) with an
      index of static cerebral autoregulation (sRoR). METHODS: Mx was validated in a
      prospective comparative study against sRoR, using 83 testing sessions in 17
      patients with traumatic brain injury. sRoR and Mx were calculated simultaneously
      during pharmacologically induced blood pressure variations. RESULTS: Mx was
      significantly correlated with sRoR (R = -0.78, p < 0.05). Nine patients were
      found to have failure of cerebral autoregulation, with an sRoR value < 50%. If an
      Mx value of 0.3 was used as the cut off point for failure of cerebral
      autoregulation, this index had 100% sensitivity and 90% specificity for
      demonstrating failure of autoregulation compared with the sRoR. An increase in
      cerebral blood flow velocity correlated significantly with Mx (R = 0.73, p <
      0.05) but not with cerebral perfusion pressure (R = 0.41). CONCLUSIONS: Dynamic
      and static cerebral autoregulation are significantly correlated in traumatic
      brain injury. Cerebral autoregulation can be monitored continuously, graded, and
      reliably assessed using a moving correlation analysis of cerebral perfusion
      pressure and cerebral blood flow velocity (Mx). The Mx index can be used to
      monitor cerebral blood flow regulation. It is useful in traumatic brain injury
      because it does not require any external stimulus.

PMID- 11971042
TI  - Magnetic resonance brain imaging in people with dizziness: a comparison with non
      dizzy people.
AB  - BACKGROUND: Dizziness is a common symptom affecting about 30% of people over the
      age of 65. OBJECTIVE: To investigate the hypothesis that structural abnormalities
      of the brain and cervical cord are more common in dizzy than in non-dizzy
      subjects. METHODS: A case-control study of subjects over the age of 65 with and
      without dizziness: 125 dizzy subjects and 86 non-dizzy subjects were recruited
      from the community through articles in the local press. Magnetic resonance
      imaging (MRI) of the brain and neck was performed, and was read by a consultant
      neuroradiologist blind to the clinical details. RESULTS: All dizzy subjects and
      all controls had at least one structural abnormality. Cerebral atrophy was found
      in 86% of dizzy subjects and 85% controls (p = 1.0) At least one white matter
      lesion was found in 69% of dizzy subjects and 78% controls (p = 0.21). White
      matter lesions in the midbrain were more common in dizzy than in non-dizzy
      subjects (22% v 4%, p < 0.001). There were no significant differences in the
      prevalence of cord compression, cervical subluxation, facet joint degeneration,
      vertebral artery compression, or vertebral artery occlusion between dizzy and non
      dizzy subjects. CONCLUSIONS: Structural abnormalities of the brain and neck are
      common in both dizzy and non-dizzy subjects. "Routine" MRI is unlikely to reveal
      a specific cause for dizziness. The observation of more frequent white matter
      lesions in the midbrain in dizzy subjects requires further study to determine
      whether small vessel changes could cause dizziness in older people.

PMID- 11971043
TI  - Is cardiovascular disease a risk factor in the development of axonal
      polyneuropathy?
AB  - OBJECTIVES: To determine if cardiovascular disease may be a risk factor in the
      development of chronic idiopathic axonal polyneuropathy (CIAP). METHODS: In this
      incidence case-control study, the prevalence of cardiovascular disease and risk
      factors in 97 patients with CIAP (mean age 67.5 (SD 7.9) years) and the
      prevalence of neuropathic features in 97 patients with peripheral arterial
      disease (PAD) (mean age 67.1 (SD 7.3) years) were investigated. The results were
      compared with those for 96 age and sex matched controls without diagnosed PAD or
      polyneuropathy (mean age 67.5 (SD 9.1) years). In a randomly chosen subgroup of
      23 patients with CIAP, 42 patients with PAD, and 48 controls, an
      electrodiagnostic investigation was performed. RESULTS: Patients with CIAP more
      often had manifest cardiovascular disease and cardiovascular risk factors than
      controls (stroke 18% v 6% of patients, odds ratio (OR) 3.2 (95% confidence
      interval (CI) 1.8 to 5.9); heart disease 29% v 15%, OR 2.4 (95% CI 1.2 to 4.9);
      family history of cardiovascular disease 42% v 21%, OR 2.8 (95% CI (1.5 to 5.2);
      hypertension 56% v 39%, OR 2.0 (95% CI 1.1 to 3.6); hypercholesterolaemia 46% v
      21%, OR 3.3 (95% CI 1.5 to 7.3); current smoking 38% v 23%, OR 2.1 (95% CI 1.1 to
      3.9)). The prevalence of cardiovascular disease and cardiovascular risk factors
      was lower than in patients with PAD. Patients with PAD more often had
      polyneuropathy than controls (15% v 5%, OR 3.3 (95% CI 1.1 to 10.0)). There was a
      trend towards lower nerve conduction velocities and lower amplitudes on
      electrodiagnostic investigation compared with controls. CONCLUSION: This study
      shows that cardiovascular disease and CIAP often coexist, and therefore
      cardiovascular disease may be a cofactor in the development of CIAP.

PMID- 11971044
TI  - Cheyne-Stokes respiration.

PMID- 11971045
TI  - Clinimetric evaluation of a new overall disability scale in immune mediated
      polyneuropathies.
AB  - OBJECTIVES: To determine the validity, reliability, and responsiveness of a new
      overall disability sum score in immune mediated polyneuropathies. METHODS: Three
      impairment measures (MRC sum score, sensory sum score, grip strength
      (Vigorimeter)) and three disability scales (an overall disability sum score
      (ODSS), Hughes' functional scale (f score), Rankin scale) were assessed in a
      cross sectional group of 113 clinically stable patients (83 with Guillain-Barre
      syndrome, 22 with chronic inflammatory demyelinating polyneuropathy (CIDP), eight
      with a gammopathy related polyneuropathy). The ODSS was also used serially in 20
      patients with recently diagnosed Guillain-Barre syndrome (n = 7) or CIDP (n = 13)
      and changing clinical conditions. Multiple regression studies were performed to
      compare the impact of impairment disturbances (independent variables) on the
      various disability scales (dependent variable). RESULTS: Moderate to good
      construct validity (stable group: Spearman's rank test (absolute values), r =
      0.41-0.79; longitudinal group: multiple correlation coefficient, R = 0.69-0.89; p
      < 0.006 for all associations) and reliability (intraclass correlation
      coefficient, R = 0.90-0.95; p < 0.0001) were demonstrated for the ODSS. Its SRM
      values were high (> 0.8), indicating good responsiveness. Impairment measures
      accounted for a higher variance proportion of the ODSS compared with the f score
      and Rankin (R = 0.64 v 0.56 and 0.45, respectively). CONCLUSIONS: All clinimetric
      requirements were met by the overall (arm and leg) disability sum score in immune
      mediated polyneuropathies. Its use is therefore suggested in evaluating immune
      mediated polyneuropathies.

PMID- 11971046
TI  - Qualitative performance characteristics differentiate dementia with Lewy bodies
      and Alzheimer's disease.
AB  - OBJECTIVES: To determine whether dementia with Lewy bodies (DLB) and Alzheimer's
      disease (AD) can be differentiated on the basis of qualitative performance
      characteristics during neuropsychological evaluation. METHODS: Forty one patients
      with clinically defined DLB were matched with 26 patients with AD for age,
      illness duration, nature and severity of cognitive deficits, and regional blood
      flow distribution on SPECT. The presence or absence of a set of qualitative
      performance characteristics, observed and recorded during the patients' initial
      cognitive evaluation, was identified by retrospective analysis of patients'
      records and the groups compared. RESULTS: Inattention, visual distractibility,
      impairments in establishing and shifting mental set, incoherence, confabulatory
      responses, perseveration, and intrusions were significantly more common in DLB
      than AD. Intrusions were particularly common in DLB, occurring in 78% of the
      group. They included externally cued intrusions arising from the visual
      environment, a feature never seen in AD. In a stepwise logistic regression
      analysis impaired mental set shifting, perseveration, and the presence of
      intrusions correctly classified 79% of patients. CONCLUSION: It is possible to
      differentiate DLB and AD on the basis of qualitative features of performance. As
      many features are amenable to detection at clinical interview, they ought to
      contribute to clinicians' diagnostic armoury, leading to improved clinical
      recognition of DLB.

PMID- 11971047
TI  - What are the determinants of quality of life in people with cervical dystonia?
AB  - BACKGROUND: Little is known about the quality of life in patients with cervical
      dystonia, although pain and depression are relatively common. OBJECTIVE: To test
      the hypothesis that an individual's ability to cope with the disease will modify
      the association of intrinsic, extrinsic, and disease related factors with quality
      of life. METHODS: Patients with cervical dystonia diagnosed by a movement
      disorder specialist were recruited from seven European countries. Data on quality
      of life (SF-36), measures of coping, and intrinsic, extrinsic, and disease
      related factors were collected by a self completed postal questionnaire. RESULTS:
      289 patients (101 men and 188 women), mean age 55 years, completed the
      questionnaire. Both physical and mental quality of life scores were predicted by
      self esteem and self deprecation, educational level, employment status, social
      support, response to botulinum toxin, disease severity, social participation,
      stigma, acceptance of illness, anxiety, and depression. In multivariable
      analyses, the strongest predictors were anxiety and depression. Severe depression
      was associated with a 19.1 point decrement in the physical summary score (95%
      confidence interval, -31.7 to -6.6; p = 0.003); however, disease duration and
      severity remained predictors. CONCLUSIONS: Care for patients with cervical
      dystonia must not only focus on reducing the severity of the dystonia but also on
      the psychological wellbeing of the patient. Interventions aimed at treating
      depression or anxiety, especially of a cognitive nature, may have a large impact
      on improving quality of life.

PMID- 11971048
TI  - Psychiatric illness and subsequent traumatic brain injury: a case control study.
AB  - OBJECTIVE: To determine whether psychiatric illness is a risk factor for
      subsequent traumatic brain injury (TBI). METHODS: Case control study in a large
      staff model health maintenance organisation in western Washington State. Patients
      with TBI, determined by International classification of diseases, 9th revision,
      clinical modification (ICD-9-CM) diagnoses, were 1440 health plan members who had
      TBI diagnosed in 1993 and who had been enrolled in the previous year, during
      which no TBI was ascertained. Three health plan members were randomly selected as
      control subjects, matched by age, sex, and reference date. Psychiatric illness in
      the year before the TBI reference date was determined by using computerised
      records of ICD-9-CM diagnoses, psychiatric medication prescriptions, and
      utilisation of a psychiatric service. RESULTS: For those with a psychiatric
      diagnosis in the year before the reference date, the adjusted relative risk for
      TBI was 1.7 (95% confidence interval (CI) 1.4 to 2.0) compared with those without
      a psychiatric diagnosis. Patients who had filled a psychiatric medication
      prescription had an adjusted relative risk for TBI of 1.6 (95% CI 1.2 to 2.1)
      compared with those who had not filled a psychiatric medication prescription.
      Patients who had utilised psychiatric services had an adjusted relative risk for
      TBI of 1.3 (95% CI 1.0 to 1.6) compared with those who had not utilised
      psychiatric services. The adjusted relative risk for TBI for patients with
      psychiatric illness determined by any of the three psychiatric indicators was 1.6
      (95% CI 1.4 to 1.9) compared with those without any psychiatric indicator.
      CONCLUSION: Psychiatric illness appears to be associated with an increased risk
      for TBI.

PMID- 11971049
TI  - Quantitative analysis of the velocity related pathophysiology of spasticity and
      rigidity in the elbow flexors.
AB  - OBJECTIVE: To quantify velocity dependent and position related properties of
      increased muscle tone measured during a constant velocity stretch. METHODS: Elbow
      flexors were vertically stretched under four different velocities (40, 80, 120,
      and 160 degrees /s) through a 75 degrees range of motion in 12 patients with
      hemiparesis, 16 with parkinsonism, and 12 normal controls. From reactive torque
      measurement, a linear second order model was adopted to dissociate velocity
      dependent viscous and velocity independent elastic components. The averaged speed
      dependent reflex torque (ASRT)--defined as the deviation of measured torque from
      baseline torque--was used to quantify the viscous component of hypertonia.
      Velocity sensitivity of ASRT (VASRT) and segmented ASRT (SASRT), derived from the
      slope of the regression line among ASRT velocity plots and from segmentations of
      reactive torque, respectively, were used to differentiate the increased muscle
      tone of spasticity and rigidity. RESULTS: ASRT and VASRT were significantly
      higher in both spasticity and rigidity than in normal controls. SASRT analysis
      showed three different position related patterns among spasticity, rigidity, and
      normal groups: spasticity showed progressively increasing muscle tension relative
      to position; rigidity showed increased (relative to the norm) but constant muscle
      tone over the entire stretch range; the normal control group showed a
      consistently low reactive torque over the entire range. CONCLUSIONS: Velocity
      dependence analysis indicates that rigidity and spasticity have approximately
      equal velocity dependent properties. For differentiating these two types of
      hypertonia, position dependent properties my be employed.

PMID- 11971050
TI  - Diagnostic value of history and physical examination in patients suspected of
      lumbosacral nerve root compression.
AB  - OBJECTIVE: To evaluate patient characteristics, symptoms, and examination
      findings in the clinical diagnosis of lumbosacral nerve root compression causing
      sciatica. METHODS: The study involved 274 patients with pain radiating into the
      leg. All had a standardised clinical assessment and magnetic resonance (MR)
      imaging. The associations between patient characteristics, clinical findings, and
      lumbosacral nerve root compression on MR imaging were analysed. RESULTS: Nerve
      root compression was associated with three patient characteristics, three
      symptoms, and four physical examination findings (paresis, absence of tendon
      reflexes, a positive straight leg raising test, and increased finger-floor
      distance). Multivariate analysis, analysing the independent diagnostic value of
      the tests, showed that nerve root compression was predicted by two patient
      characteristics, four symptoms, and two signs (increased finger-floor distance
      and paresis). The straight leg raise test was not predictive. The area under the
      curve of the receiver-operating characteristic was 0.80 for the history items. It
      increased to 0.83 when the physical examination items were added. CONCLUSIONS:
      Various clinical findings were found to be associated with nerve root compression
      on MR imaging. While this set of findings agrees well with those commonly used in
      daily practice, the tests tended to have lower sensitivity and specificity than
      previously reported. Stepwise multivariate analysis showed that most of the
      diagnostic information revealed by physical examination findings had already been
      revealed by the history items.

PMID- 11971051
TI  - Familial adult onset of Krabbe's disease resembling hereditary spastic paraplegia
      with normal neuroimaging.
AB  - Krabbe's disease (globoid cell leucodystrophy) is a disorder involving the white
      matter of the peripheral and central nervous systems. Mutations in the gene for
      the lysosomal enzyme galactocerebrosidase (GALC) result in low enzymatic activity
      and decreased ability to degrade galactolipids found in myelin. The disease is
      classically of infantile onset, but adult onset cases have been reported.
      Magnetic resonance imaging (MRI) of the brain shows characteristic abnormalities.
      A unique family with Krabbe's disease is described, with proven GALC deficiency
      but normal MRI. A neurological phenotype is present in heterozygotes and the
      family shows the extent of homozygotic phenotypic diversity that can be seen in
      this disorder.

PMID- 11971052
TI  - Apolipoprotein E polymorphism in German patients with frontotemporal
      degeneration.
AB  - OBJECTIVES: The apolipoprotein E (apoE) polymorphism, designated as epsilon2,
      epsilon3, epsilon4, is a genetic risk factor associated with several forms of
      dementia. Inconclusive results have been reported in patients with frontotemporal
      degeneration which prompted this study of the apoE polymorphism in a German
      sample with frontotemporal degeneration. METHODS: the frequencies of the epsilon2
      and epsilon4 alleles and the effect of these alleles on the age at onset in 52
      patients with frontotemporal degeneration who underwent a thorough diagnostic
      examination and in 182 cognitively healthy age matched controls were assessed.
      Genotype comparisons between the groups were performed using multiple logistic
      regression analysis. Ages at onset according to the apoE genotype were compared
      by linear regression analysis. RESULTS: In patients with frontotemporal
      degeneration apoE epsilon2 and epsilon4 allele frequencies were 9.6% each,
      whereas the corresponding frequencies in controls were 9.6% and 9.9%,
      respectively. There was no significant difference in either epsilon2 or epsilon4
      allele frequency between the groups. Age at onset was highest in patients with
      the epsilon2/epsilon3 genotype (61.3 years) followed by patients with the
      epsilon3/epsilon3 (58.3 years) and was lowest in patients with the
      epsilon3/epsilon4 genotype (56.4 years) but the differences failed to reach
      statistical significance. CONCLUSION: Allelic variants of the apoE gene do not
      modulate occurrence or age at onset in this sample of German patients with
      frontotemporal degeneration.

PMID- 11971053
TI  - Serum leptin level in women with idiopathic intracranial hypertension.
AB  - Leptin is a protein secreted by adipose cells which influences regulation of
      energy balance and body weight. Idiopathic intracranial hypertension (IIH) is
      recognised as a neurological disorder mainly affecting obese females. The aim of
      this study was to evaluate the association between IIH and serum leptin level in
      15 obese patients and compare the results with those for 16 obese and 15 non
      obese women. A significantly higher serum leptin level was found in patients with
      IIH than in controls (p<0.0001), and this did not correlate with body mass index
      (BMI). Serum leptin levels were significantly associated with BMI in both control
      groups (p<0.0006). Additional factors must therefore be involved in the
      phenomenon of serum leptin increase beyond weight gain. The cause can only be
      hypothesised, but it seems that the origin is central, probably hypothalamic.

PMID- 11971056
TI  - Human T cell leukaemia virus type I associated neuromuscular disease causing
      respiratory failure.
AB  - Polymyositis and inclusion body myositis have rarely been described in
      association with human T cell leukaemia virus type I (HTLV-I) infection. Most of
      such patients have coexisting HTLV-I associated myelopathy (HAM). Two patients
      with HTLV-I infection, myopathy, and respiratory failure are described. The
      muscle biopsy specimen of the first patient bore the histological features of
      inclusion body myositis and there was no evidence of concurrent myelopathy. The
      second patient had HAM, and her muscle biopsy showed non-specific myopathic and
      neuropathic changes. Both patients developed respiratory muscle weakness over
      eight years after diagnosis of myopathy, leading to hypercapnic respiratory
      failure requiring mechanical ventilatory support. Respiratory failure as a
      complication of HTLV-I associated myopathy has not previously been described.

PMID- 11971055
TI  - Anticardiolipin antibodies in patients with multiple sclerosis do not represent a
      subgroup of patients according to clinical, familial, and biological
      characteristics.
AB  - BACKGROUND: In multiple sclerosis (MS), case control studies have shown that
      anticardiolipin antibodies (aCL Ab) are more frequent than in the general
      population and that aCL Ab positivity may be associated with specific clinical
      characteristics. OBJECTIVES: To determine whether patients with MS who are
      positive for aCL Ab have specific characteristics. METHODS: 285 consecutive
      patients with MS were tested for aCL Ab positivity. Patients also underwent
      complete autoimmune screening and were systematically evaluated for clinical
      characteristics and individual or family history of autoimmune disease. RESULTS:
      aCL Ab positivity was found in 42 patients (15%). The main isotype was aCL IgM
      (32 patients, 11%). Demographics and clinical characteristics including sex, age
      at onset, course of the disease, expanded disability status scale score, and
      progression index were not different between aCL Ab positive and aCL Ab negative
      patients. Clinical systems involved at onset or during the course of the disease
      were not different from what is usually observed in MS. aCL Ab positivity was not
      associated with an increased frequency of autoimmune disease and was not
      predictive of a family history of autoimmune disease. Patients positive for aCL
      IgM were more frequently positive for the presence of non-organ specific
      antibodies (53% v 39%, respectively, p = 0.02). CONCLUSIONS: These results do not
      support the hypothesis that patients with MS with aCL Ab constitute a subgroup of
      MS according to demographic clinical and familial characteristics. The greater
      frequency of other antibodies in aCL Ab positive patients suggests that they only
      reflect a more general autoimmune activation in MS.

PMID- 11971054
TI  - Immunoadsorption inferior to plasma exchange in a patient with chronic
      inflammatory demyelinating polyradiculoneuropathy.
AB  - Staphylococcal protein A immunoadsorption and plasma exchange were compared for
      treating chronic inflammatory demyelinating polyradiculoneuropathy. In a single
      patient, plasma exchange had a more beneficial effect than immunoadsorption on
      clinical outcome measures. Serum IgM antibody activity to peripheral nerve fell
      significantly following plasma exchange. Serum IgM and IgA fell more and IgG less
      after plasma exchange than after immunoadsorption. The superior efficacy of
      plasma exchange to immunoadsorption in this case may have been the result of
      removal of an IgM antibody.

PMID- 11971057
TI  - Progressive myoclonic ataxia and JC virus encephalitis in an AIDS patient.
AB  - A case of progressive myoclonic ataxia in an AIDS patient is described, which
      evolved over a 13 month period. The ataxia persisted as the only clinical finding
      for several months before the appearance of a severe tetraparesis and cachexia.
      Throughout the clinical progression, magnetic resonance imaging (MRI) revealed
      the presence of bilateral, progressive, isolated, and symmetrical lesions
      involving the red nuclei, subthalami, thalami, lenticular nuclei, and primary
      motor cortices. Neuropathological examination, supplemented by in situ
      hybridisation for JC virus DNA, confirmed that the lesions were those of
      progressive multifocal leucoencephalopathy (PML). The exceptional clinical
      presentation of PML in this case is the first report of progressive myoclonic
      ataxia caused by PML. The selective nature of the lesions confirms the role of
      the dentato-rubral-thalamo-cortical tract in the pathogenesis of progressive
      myoclonic ataxia. The atypical MRI findings further emphasise the need for
      expanded diagnostic criteria for PML in AIDS patients and support the use of more
      aggressive diagnostic methods as new treatments become available.

PMID- 11971058
TI  - Transcranial Doppler sonography during head up tilt suggests preserved central
      sympathetic activation in familial dysautonomia.
AB  - OBJECTIVE: Cerebral autoregulation was assessed by transcranial Doppler
      sonography in 10 patients with familial dysautonomia and 10 age matched controls.
      METHODS: Blood pressure, heart rate, and middle cerebral artery blood flow
      velocity (CBFV) were simultaneously recorded when supine and during 180 seconds
      of head up tilt. Cerebrovascular resistance (CVR) was calculated from CBFV and
      mean blood pressure was adjusted to brain level. RESULTS: In the controls, mean
      blood pressure remained stable during tilt, but heart rate increased
      significantly. In the patients with familial dysautonomia, mean (SD) blood
      pressure decreased by 15.0 (10.8)% (p < 0.05). Heart rate remained unchanged. In
      controls, systolic and mean CBFV decreased by 9.1 (4.7)% and 9.4 (7.0)%,
      respectively, while diastolic CBFV remained stable. In the patients, diastolic
      and mean CBFV decreased continuously by 32.1 (13.9)% and by 14.8 (31.4)%. Supine
      CVR was 28% higher in patients than in controls and decreased significantly less
      during head up tilt. CONCLUSIONS: Tilt evokes orthostatic hypotension without
      compensatory tachycardia in patients with familial dysautonomia owing to
      decreased peripheral sympathetic innervation. High supine CVR values and
      relatively preserved CVR during tilt suggest preserved central sympathetic
      activation in familial dysautonomia, assuring adaptation of cerebrovascular
      autoregulation to chronic supine hypertension and orthostatic hypotension.

PMID- 11971059
TI  - Sleep symptoms and polysomnographic architecture in advanced Parkinson's disease
      after chronic bilateral subthalamic stimulation.
AB  - OBJECTIVE: To evaluate the sleep symptoms and polysomnographic architecture in
      advanced Parkinson's disease after chronic bilateral subthalamic stimulation (STN
      DBS). METHODS: Sleep was studied in 11 patients (six women and five men; mean
      (SD) age 63.6 (7.8) years) who underwent STN-DBS. Subjective sleep evaluation was
      assessed by clinical sleep interview and the Pittsburgh sleep quality index
      (PSQI) questionnaire, and sleep architecture by polysomnography with audiovisual
      recording. Nocturnal mobility was evaluated. RESULTS: Before surgery, eight
      patients rated their sleep quality as unsatisfactory; seven of these had a marked
      improvement after surgery, and the PSQI questionnaire showed significantly
      improved sleep quality. After surgery, polysomnography showed an increase in the
      longest period of uninterrupted sleep and a decrease in the arousal index. There
      was an increase in nocturnal mobility after surgery, but no change in REM sleep
      behaviour disorder. CONCLUSIONS: In advanced Parkinson's disease, chronic STN-DBS
      is associated with subjective improvement in sleep quality, probably through
      increased nocturnal mobility and reduction of sleep fragmentation.

PMID- 11971061
TI  - Thixotropy of levator palpebrae as the cause of lagophthalmos after peripheral
      facial nerve palsy.
AB  - Patients with facial nerve palsy are at risk of developing corneal ulceration
      because of lagophthalmos (incomplete closure of the affected eyelid).
      Lagophthalmos could result from thixotropy of the levator palpebrae muscle--that
      is, the formation of tight crossbridges between the actin and myosin filaments of
      the muscle fibres causing stiffness of the muscle--rather than from paralysis of
      the orbicularis occuli muscle as previously supposed. This possibility was
      investigated in 13 patients with a peripheral facial nerve palsy in a prospective
      open study. The levator muscle of the affected eyelid was stretched by
      manipulation and downward movement of the passively closed upper eyelid for
      approximately 15 seconds. The amount of lagophthalmos was measured before and
      immediately after this manoeuvre. In all patients except one there was a clear
      reduction in lagophthalmos (mean reduction 72%; range 60-100%). Thus in this
      setting the lagophthalmos appears to be caused by thixotropy of the levator
      palpebrae muscle, which has implications for treatment.

PMID- 11971062
TI  - Cervical subarachnoid floating cavernous malformation presenting with recurrent
      subarachnoid haemorrhage.

PMID- 11971063
TI  - Post-traumatic epilepsy in children requiring inpatient rehabilitation following
      head injury.
AB  - OBJECTIVE: To study the prevalence of, and identify possible risk factors for,
      the development of post-traumatic epilepsy in a cohort of children with severe
      head injury treated in an inpatient rehabilitation unit. METHODS: The hospital
      and community medical case notes of all children admitted prospectively to the
      unit and the records of the clinical EEG department over a seven year period were
      reviewed to identify those children who had developed late epilepsy after head
      injuries. RESULTS: 102 children received inpatient rehabilitation between 1 June
      1991 and 28 February 1998. Follow up of these patients ranged from 18 months to
      over eight years. Nine patients (9%) developed post-traumatic epilepsy between
      eight months and over five years after the head injury. Three of the nine
      patients had experienced early tonic-clonic seizures in the first week after the
      injury. Other risk factors examined included the age of the patient, the cause of
      the head injury, initial Glasgow coma scale score, neuroimaging findings, and
      duration of ventilatory support. Only the presence of early seizures (p = 0.002)
      and possibly the Glasgow coma scale score (p = 0.043) were found to be specific
      risk factors for late late epilepsy. CONCLUSIONS: Post-traumatic epilepsy appears
      to be uncommon, even in children with severe head injuries. Early seizures may
      indicate increased risk of developing late post-traumatic epilepsy in this study
      population.

PMID- 11971064
TI  - Simultaneous onset of haemorrhagic and ischaemic strokes in a haemodialysis
      patient.
AB  - Primary brain haemorrhage and infarction only very rarely occur simultaneously. A
      patient with end stage renal disease from diabetic nephropathy suddenly had motor
      aphasia and horizontal nystagmus soon after finishing haemodialysis.
      Neuroradiological studies showed a haematoma on the right side of the pons and an
      infarct in the left frontal lobe with occlusion of the left internal carotid
      artery. Specific conditions of the haemodialysis--including anticoagulant use,
      relative hypovolaemia and hypertension just before haemodialysis, and an abrupt
      decrease in blood pressure during haemodialysis--seemed to be the major reason
      for the simultaneous onset of dual strokes.

PMID- 11971065
TI  - Apolipoprotein E and neurocognitive outcome from coronary artery surgery.

PMID- 11971066
TI  - Japanese cases of familial hemiplegic migraine with cerebellar ataxia carrying a
      T666M mutation in the CACNA1A gene.

PMID- 11971067
TI  - Interferon beta-1a treatment of corticosteroid sensitive polymyositis.

PMID- 11971068
TI  - Cellular schwannoma of the posterior fossa.

PMID- 11971069
TI  - Multiple cerebral aneurysms and the Diamond-Blackfan syndrome.

PMID- 11971070
TI  - Plasmapheresis and Miller Fisher syndrome: analysis of 50 consecutive cases.

PMID- 11971071
TI  - Conflict of intentions or inner negativism?

PMID- 11971072
TI  - Apomorphine as an alternative to sildenafil in Parkinson's disease.

PMID- 11971075
TI  - Does training change the brain?

PMID- 11971077
TI  - Intermediate filaments: a common thread in neuromuscular disorders.

PMID- 11971078
TI  - RITE performance predicts outcome on the ABPN Part I examination.
AB  - OBJECTIVE: This study examined the performance correlation the American Academy
      of Neurology Resident Inservice Training Examination (RITE) and Part I of the
      American Board of Psychiatry and Neurology (ABPN) examination. METHODS:
      Candidates who took the RITE in the last year of training were tracked and their
      subsequent performance on the ABPN Part I examination was compared with their
      performance on the RITE. RESULTS: Performance on the RITE is predictive of
      performance on the ABPN Part I examination. CONCLUSIONS: The RITE can be used to
      assess a resident's readiness to take the ABPN Part I examination.

PMID- 11971079
TI  - MRI techniques to monitor MS evolution: the present and the future.
AB  - Conventional MRI (cMRI) is limited in its ability to provide specific information
      about pathology in MS. Measures commonly derived from cMRI include T2 lesions, T1
      enhanced lesions, atrophy, and possibly T1-hypointense lesions, which have been
      extensively investigated in many clinical trials. Better MRI measures are needed
      to advance our understanding of MS and design ideal clinical trials. This article
      reviews the strengths and weaknesses of the major MRI-based methods used to
      monitor MS evolution and submits that 1) metrics derived from magnetization
      transfer MRI, diffusion-weighted MRI, and proton MRS should be implemented to
      achieve reliable specific in vivo quantification of MS pathology; 2) targeted
      multiparametric MRI protocols rather than generic application of cMRI should be
      used in all possible clinical circumstances and trials; and 3) reproducible
      quantitative MR measures should ideally be used for the assessment of patients
      but are essential for clinical trials.

PMID- 11971080
TI  - Caffeinated clues and the promise of adenosine A(2A) antagonists in PD.
AB  - Large prospective epidemiologic studies have linked the consumption of coffee and
      other caffeinated beverages to a reduced risk of subsequently developing PD.
      Caffeine as well as more specific antagonists of the adenosine A(2A) receptor
      have also now been found to attenuate neurotoxicity in a mouse model of PD. The
      convergence of these epidemiologic and laboratory data supports the possibility
      that caffeine may reduce the risk of developing PD. However, a neuroprotective
      effect of caffeine in PD remains unproven; current evidence does not provide a
      rational basis for recommending caffeine consumption to modify the risk or
      progression of PD. In addition to possessing neuroprotective potential, caffeine
      and other A(2A) antagonists have long been known to acutely reverse motor
      deficits in a variety of PD models. This symptomatic antiparkinsonian benefit of
      blocking A(2A) receptors, coupled with their remarkably restricted expression in
      the basal ganglia, have made A(2A) antagonists attractive targets for drug
      development. Now, with the prospect of a neuroprotective bonus, the novel
      therapeutic potential of A(2A) antagonists appears all the more promising just as
      they are entering clinical trials for PD.

PMID- 11971081
TI  - Clinical features of frontotemporal dementia due to the intronic tau 10(+16)
      mutation.
AB  - OBJECTIVE: To describe the clinical features of nine British families with
      neuropathologically verified frontotemporal dementia (FTD) due to the intronic
      tau exon 10(+16) mutation. METHODS: Retrospective chart reviews of family members
      with FTD belonging to nine tau 10(+16) mutation pedigrees in whom neuropathologic
      examination had been carried out. APOE genotype was determined for those patients
      for whom DNA was available. RESULTS: The median age at onset was 50 years (range
      37 to 59 years; n = 30). The median age at death was 61 years (range 42 to 72
      years; n = 33). The median duration of the disease was 11 years (range 3 to 22
      years; n = 25) for those who have died and is 17 years (range 15 to 23 years; n =
      3) for those living. The most common presenting symptom was disinhibition (n =
      23). A minority presented with frontal dysexecutive symptoms, apathy, impairment
      of episodic memory, or depression. All of these patients subsequently developed
      personality and behavioral change. Memory impairment, language deficits,
      ritualistic behavior, hyperphagia, and hyperorality were frequent symptoms.
      Parkinsonism, neuroleptic sensitivity, or primitive reflexes were present in half
      of the patients, where these data were available. The clinical features of ALS
      were absent. Neuropathologic examination of 12 patients demonstrated the hallmark
      tau-positive neuronal and glial inclusions. APOE genotype did not account for the
      considerable variation in age at onset, age at death, duration of disease, or
      severity of estimated brain atrophy. CONCLUSIONS: All cases fulfilled the
      clinical criteria for a diagnosis of FTD. Despite similar clinical phenotypes,
      there was considerable variation in age at onset and duration of disease both
      between and within families, suggesting the presence of an effect due to other
      genetic or environmental factors.

PMID- 11971082
TI  - Neuropathologic variation in frontotemporal dementia due to the intronic tau
      10(+16) mutation.
AB  - BACKGROUND: An increasing number of recently described tau mutations show
      considerable clinical heterogeneity. The assessment of this phenotypic variation
      is of vital importance in the differential diagnosis of neurodegenerative
      diseases. OBJECTIVE: To assess the neuropathologic heterogeneity in a
      comprehensive study of 12 brains with a tau mutation at exon 10(+16) (C-to-T)
      splice site from 9 families. METHODS: A comprehensive neuropathologic examination
      has been carried out, using a wide range of tau antibodies. RESULTS: All brains
      showed frontotemporal atrophy of varying severity and pallor of the pigmented
      nuclei of the brainstem. The histologic changes were more extensive to include
      other cortical areas, the deep gray matter, and the white matter. The hallmark
      histologic lesions were the tau-positive neuronal and glial inclusions. In
      neurons, these ranged from typical neurofibrillary tangles through well
      circumscribed inclusions to diffuse cytoplasmic staining. This tau pathology was
      complemented by the presence of large, abnormal achromatic neurons, neuronal
      loss, astrocytosis, and superficial status spongiosus. CONCLUSION: The
      distribution, type, and severity of these histologic abnormalities varied not
      only from case to case but also within the same brain. These brains with a common
      tau mutation raise important differential diagnostic problems: cases in the past
      might have been misdiagnosed as corticobasal degeneration or even atypical Pick
      disease, disorders with similar, if not identical, phenotypic manifestations.

PMID- 11971083
TI  - The relationship of hypertension in the elderly to AD, vascular dementia, and
      cognitive function.
AB  - BACKGROUND: Hypertension at the age of 45 to 50 years may predispose to AD later
      in life. It is not known whether hypertension after age 65 years also contributes
      to AD risk, and its effect on cognitive function is also not fully understood.
      METHODS: Data were analyzed from 1,259 Medicare recipients free of dementia in a
      longitudinal study covering a 7-year period (1991 to 1998). The effect of
      hypertension was first examined in relationship to the risk for incident AD and
      then to incident vascular dementia (VaD) using Cox proportional hazards models.
      Changes in performance over time on tasks of memory, language, and
      visuospatial/cognitive function were compared in those with and without
      hypertension using generalized estimating equations. RESULTS: Of the 1,259
      subjects, 731 (58.1%) had a history of hypertension associated with diabetes,
      stroke, and heart disease. A history of hypertension was not associated with an
      increased risk for AD (rate ratio [RR] 0.9, 95% CI 0.7 to 1.3) but was associated
      with an increased risk for VaD (1.8 [1.0 to 3.2]). Hypertension was not
      associated with changes in memory, language, and general cognitive function in
      normal individuals over time. Compared with individuals with neither hypertension
      nor heart disease, those with hypertension or heart disease alone had no increase
      in risk for VaD. However, when both were present, there was a threefold increase
      in risk for VaD. A sixfold increase in risk was observed when both hypertension
      and diabetes were present. CONCLUSIONS: Hypertension after age 65 years is not
      associated with AD and does not adversely affect memory, language, or general
      cognitive function. A history of hypertension may be an antecedent to VaD,
      particularly in the presence of heart disease or diabetes.

PMID- 11971085
TI  - MRI measures of entorhinal cortex vs hippocampus in preclinical AD.
AB  - BACKGROUND: MRI measures of the entorhinal cortex and the hippocampus have been
      used to predict which nondemented individuals with memory problems will progress
      to meet criteria for AD on follow-up, but their relative accuracy remains
      controversial. OBJECTIVES: To compare MRI measures of the entorhinal cortex and
      the hippocampus for predicting who will develop AD. METHODS: MRI volumes of the
      entorhinal cortex and the hippocampus were obtained in 137 individuals comprising
      four groups: 1) individuals with normal cognition both at baseline and after 3
      years of follow-up (n = 28), 2) subjects with memory difficulty but not dementia
      both at baseline and after 3 years of follow-up (n = 73), 3) subjects with memory
      difficulty at baseline who were diagnosed with probable AD within 3 years of
      follow-up (n = 21), and 4) patients with mild AD at baseline (n = 16). RESULTS:
      Measures of both the entorhinal cortex and the hippocampus were different for
      each of the pairwise comparisons between the groups (p < 0.001) and were
      correlated with tests of memory (p < 0.01). However, the volume of the entorhinal
      cortex differentiated the subjects from those destined to develop dementia with
      considerable accuracy (84%), whereas the measure of the hippocampus did not.
      CONCLUSION: These findings are consistent with neuropathologic data showing
      substantial involvement of the entorhinal cortex in the preclinical phase of AD
      and suggest that, as the disease spreads, atrophic change develops within the
      hippocampus, which is measurable on MRI.

PMID- 11971084
TI  - Association between the APOE genotype and psychopathologic symptoms in
      Alzheimer's disease.
AB  - BACKGROUND: Psychiatric symptoms occur frequently in the course of AD, are a
      frequent contributor to institutionalization, predict cognitive decline and
      death, and often require treatment with psychotropic medications. Previous
      studies investigating the association between APOE genotype and psychiatric
      symptomatology in AD have reported contradictory results. OBJECTIVE: To determine
      whether APOE genotype predicts incident psychiatric symptomatology in patients
      with AD. METHODS: Eighty-seven patients with AD at early stages and no
      psychiatric history were followed semiannually for up to 9.3 years (mean 5.5
      years) for development of delusions, illusions, hallucinations, behavioral
      symptoms, and depression. Cox proportional hazards models were used to examine
      the relative risk for incident psychiatric symptomatology (outcome) in relation
      to APOE genotype (predictor). RESULTS: The presence of one epsilon4 allele
      carried a 2.5-fold risk, whereas the presence of two epsilon4 alleles carried a
      5.6-fold risk for development of delusions. The associations remained significant
      even when age, ethnicity, sex, education, duration of disease, and cognitive and
      functional performance were controlled for. The presence of two epsilon4 alleles
      was associated with reduced risk for developing hallucinations in the adjusted
      analysis only. No significant associations were detected between APOE genotype
      and the incidence of illusions, behavioral symptoms, or depression. CONCLUSION:
      The presence of one or more epsilon4 alleles is a significant predictor for the
      incidence of delusions in the course of AD.

PMID- 11971086
TI  - Women at risk for AD show increased parietal activation during a fluency task.
AB  - BACKGROUND: Imaging studies have shown disparities in resting metabolism and in
      functional activation between cognitively normal individuals at high and low risk
      for AD. A recent study has shown increased parietal activation in high-risk
      subjects during a paired associates recall task, which the authors postulated
      might overlap activation typically observed in verbal fluency. OBJECTIVE: To
      determine whether parietal activation is altered in a letter fluency task in
      cognitively normal individuals at high risk for AD. METHODS: fMRI was used to
      compare cortical activation between two groups of cognitively normal women
      differing in their risk for developing AD. A letter fluency task was used, which
      activates left frontal and parietal regions. The risk groups differed in family
      history of AD and APOE allele status but were matched in age, education, and
      measures of cognitive performance. Average age of the study participants was 53
      years. RESULTS: The regional patterns of brain activation were similar between
      groups and similar to patterns observed by other investigators. However, the high
      risk group showed significantly increased activation in the left parietal region
      despite identical letter fluency performance between risk groups. CONCLUSIONS:
      Cognitively normal individuals at high risk for AD show increased brain
      activation in the left parietal region with letter fluency, a region adjacent to
      that observed by others using a recall task. This convergence of results
      indicates disruption of functional circuits involving the left parietal lobe in
      asymptomatic individuals at increased risk for AD.

PMID- 11971088
TI  - Dyslexia-specific brain activation profile becomes normal following successful
      remedial training.
AB  - OBJECTIVES: To examine changes in the spatiotemporal brain activation profiles
      associated with successful completion of an intensive intervention program in
      individual dyslexic children. METHODS: The authors obtained magnetic source
      imaging scans during a pseudoword reading task from eight children (7 to 17 years
      old) before and after 80 hours of intensive remedial instruction. All children
      were initially diagnosed with dyslexia, marked by severe difficulties in word
      recognition and phonologic processing. Eight children who never experienced
      reading problems were also tested on two occasions separated by a 2-month
      interval. RESULTS: Before intervention, all children with dyslexia showed
      distinctly aberrant activation profiles featuring little or no activation of the
      posterior portion of the superior temporal gyrus (STGp), an area normally
      involved in phonologic processing, and increased activation of the corresponding
      right hemisphere area. After intervention that produced significant improvement
      in reading skills, activity in the left STGp increased by several orders of
      magnitude in every participant. No systematic changes were obtained in the
      activation profiles of the children without dyslexia as a function of time.
      CONCLUSIONS: These findings suggest that the deficit in functional brain
      organization underlying dyslexia can be reversed after sufficiently intense
      intervention lasting as little as 2 months, and are consistent with current
      proposals that reading difficulties in many children represent a variation of
      normal development that can be altered by intensive intervention.

PMID- 11971089
TI  - Neuropsychiatric syndromes in lupus: prevalence using standardized definitions.
AB  - OBJECTIVE: The San Antonio Lupus Study of Neuropsychiatric Disease is a
      longitudinal study designed to characterize the spectrum of and important risk
      factors for specific neuropsychiatric systemic lupus erythematosus (NPSLE)
      syndromes. METHODS: Subjects must meet criteria for SLE and must be at least 18
      years of age. A standardized medical history, neurologic, rheumatologic, and
      psychiatric examinations, computerized neuropsychological evaluation, and
      serologic testing are performed. RESULTS: This report is based on the first 128
      subjects (120 women and 8 men) who completed the initial study visit. Data from
      this initial study visit were evaluated for the prevalence of NPSLE using the
      American College of Rheumatology case definitions for 19 NPSLE syndromes. One or
      more NPSLE syndromes were present in 80% of subjects: cerebrovascular disease (2,
      2%; ischemic stroke); headaches (73, 57%); mononeuropathy (9, 8%; median 8, ulnar
      1); movement disorder (1, 1%; chorea); neuropathy, cranial (2, 2%; trigeminal);
      polyneuropathy (29, 22%; sensorimotor); seizures (21, 16%; partial); anxiety
      disorder (27, 24%); major depressive-like episode (37, 28%); mood disorder with
      depressive features (21, 19%); mood disorder with manic features (3, 3%); mood
      disorder with mixed features (1, 1%); psychosis (6, 5%). In a subset of 67
      patients who received standardized neuropsychological testing, 21% had normal
      results. In the remainder, the following levels of impairment were seen: 43%
      mild, 30% moderate, and 6% severe. CONCLUSIONS: The prevalence of NPSLE was high
      in this cohort of unselected patients with SLE. Headaches, cognitive dysfunction,
      and psychiatric disorders were the most common NPSLE syndromes seen. These
      results will be easily comparable to other studies also using standardized
      diagnostic criteria. However, the lack of ethnicity and language-matched
      normative neuropsychological data may make comparisons of cognitive dysfunction
      in SLE populations difficult.

PMID- 11971091
TI  - Contrasts in cortical magnesium, phospholipid and energy metabolism between
      migraine syndromes.
AB  - BACKGROUND: Previous single voxel (31)P MRS pilot studies of migraine patients
      have suggested that disordered energy metabolism or Mg(2+) deficiencies may be
      responsible for hyperexcitability of neuronal tissue in migraine patients. These
      studies were extended to include multiple brain regions and larger numbers of
      patients by multislice (31)P MR spectroscopic imaging. METHODS: Migraine with
      aura (MWA), migraine without aura (MwoA), and hemiplegic migraine patients were
      studied between attacks by (31)P MRS imaging using a 3-T scanner. RESULTS:
      Results were compared with those in healthy control subjects without headache. In
      MwoA, consistent increases in phosphodiester concentration [PDE] were measured in
      most brain regions, with a trend toward increase in [Mg(2+)] in posterior brain.
      In MWA, phosphocreatine concentration ([PCr]) was decreased to a minor degree in
      anterior brain regions and a trend toward decreased [Mg(2+)] was observed in
      posterior slice 1, but no consistent changes were found in phosphomonoester
      concentration [PME], [PDE], inorganic phosphate concentration ([Pi]), or pH. In
      hemiplegic migraine patients, [PCr] had a tendency to be lower, and [Mg(2+)] was
      significantly lower than in the posterior brain regions of control subjects.
      Trend analysis showed a significant decrease of brain [Mg(2+)] and [PDE] in
      posterior brain regions with increasing severity of neurologic symptoms.
      CONCLUSIONS: Overall, the results support no substantial or consistent
      abnormalities of energy metabolism, but it is hypothesized that disturbances in
      magnesium ion homeostasis may contribute to brain cortex hyperexcitability and
      the pathogenesis of migraine syndromes associated with neurologic symptoms. In
      contrast, migraine patients without a neurologic aura may exhibit compensatory
      changes in [Mg(2+)] and membrane phospholipids that counteract cortical
      excitability.

PMID- 11971090
TI  - The humoral response in the pathogenesis of gluten ataxia.
AB  - OBJECTIVE: To characterize humoral response to cerebellum in patients with gluten
      ataxia. BACKGROUND: Gluten ataxia is a common neurologic manifestation of gluten
      sensitivity. METHODS: The authors assessed the reactivity of sera from patients
      with gluten ataxia (13), newly diagnosed patients with celiac disease without
      neurologic dysfunction (24), patients with other causes of cerebellar
      degeneration (11), and healthy control subjects (17) using indirect
      immunocytochemistry on human cerebellar and rat CNS tissue. Cross-reactivity of a
      commercial IgG antigliadin antibody with human cerebellar tissue also was
      studied. RESULTS: Sera from 12 of 13 patients with gluten ataxia stained Purkinje
      cells strongly. Less intense staining was seen in some but not all sera from
      patients with newly diagnosed celiac disease without neurologic dysfunction. At
      high dilutions (1:800) staining was seen only with sera from patients with gluten
      ataxia but not in control subjects. Sera from patients with gluten ataxia also
      stained some brainstem and cortical neurons in rat CNS tissue. Commercial anti
      gliadin antibody stained human Purkinje cells in a similar manner. Adsorption of
      the antigliadin antibodies using crude gliadin abolished the staining in patients
      with celiac disease without neurologic dysfunction, but not in those with gluten
      ataxia. CONCLUSIONS: Patients with gluten ataxia have antibodies against Purkinje
      cells. Antigliadin antibodies cross-react with epitopes on Purkinje cells.

PMID- 11971092
TI  - Acute migraine headache: possible sensitization of neurons in the spinal
      trigeminal nucleus?
AB  - OBJECTIVE: To investigate trigeminal sensory processing in patients with migraine
      using a novel "nociception-specific" blink reflex. METHODS: Seventeen patients
      with unilateral migraine headache were studied within 6 hours of onset. Blink
      reflexes were elicited with a standard stimulating electrode (standard blink
      reflex) and concentric stimulating electrode (nociception-specific blink reflex)
      during the acute migraine attack, after treatment with IV lysine acetylsalicylate
      (1,000 mg) or oral zolmitriptan (5 mg) and interictally. RESULTS: After standard
      stimulation, no differences were detected for the R1 and R2 onset latencies and
      areas under the curve (AUC) between the different time points and the headache
      and nonheadache side. Nociception-specific stimulation revealed a shortening of
      R2 onset latencies (44.3 +/- 5.4 ms for headache side vs 48.9 +/- 5.8 ms for
      nonheadache side) during the acute migraine attack compared with the headache
      free interval (49.8 +/- 5.3 vs 49.8 +/- 4.5 ms). The AUC of the R2 increased on
      the headache side by 680% and on the nonheadache side by 230% compared with the
      headache-free interval. Drug treatment parallel to pain relief increased the
      onset latencies (zolmitriptan: 48.0 +/- 8.2 ms for headache side vs 52.3 +/- 7.6
      ms for nonheadache side; lysine acetylsalicylate: 48.0 +/- 5.0 ms for headache
      side vs 51.2 +/- 5.6 ms for nonheadache side) and reduced the AUC of R2
      (zolmitriptan by 45% and lysine acetylsalicylate by 48%). CONCLUSION: The data
      suggest temporary sensitization of central trigeminal neurons during acute
      migraine attacks.

PMID- 11971094
TI  - Orthostatic hypotension from sympathetic denervation in Parkinson's disease.
AB  - BACKGROUND: Patients with PD often have signs or symptoms of autonomic failure,
      including orthostatic hypotension. Cardiac sympathetic denervation occurs
      frequently in PD, but this has been thought to occur independently of autonomic
      failure. METHODS: Forty-one patients with PD (18 with and 23 without orthostatic
      hypotension) and 16 age-matched healthy volunteers underwent PET scanning to
      visualize sympathetic innervation after injection of 6-[(18)F]fluorodopamine.
      Beat-to-beat blood pressure responses to the Valsalva maneuver were used to
      identify sympathetic neurocirculatory failure and plasma norepinephrine to
      indicate overall sympathetic innervation. RESULTS: All patients with PD and
      orthostatic hypotension had abnormal blood pressure responses to the Valsalva
      maneuver and septal and lateral ventricular myocardial concentrations of 6
      [(18)F]fluorodopamine-derived radioactivity >2 SD below the normal mean. In
      contrast, only 6 of the 23 patients without orthostatic hypotension had abnormal
      Valsalva responses (p < 0.0001 compared with patients with orthostatic
      hypotension), and only 11 had diffusely decreased 6-[(18)F]fluorodopamine-derived
      radioactivity in the left ventricular myocardium (p = 0.0004). Of the 12
      remaining patients without orthostatic hypotension, 7 had locally decreased
      myocardial radioactivity. Supine plasma norepinephrine was lower in patients with
      than in those without orthostatic hypotension (1.40 +/- 0.15 vs 2.32 +/- 0.26
      nmol/L, p = 0.005). 6-[(18)F]fluorodopamine-derived radioactivity was less not
      only in the myocardium but also in the thyroid and renal cortex of patients with
      PD than in healthy control subjects. CONCLUSIONS: In PD, orthostatic hypotension
      reflects sympathetic neurocirculatory failure from generalized sympathetic
      denervation.

PMID- 11971093
TI  - Evaluation of 50 probands with early-onset Parkinson's disease for Parkin
      mutations.
AB  - BACKGROUND: Early onset PD has been associated with different mutations in the
      Parkin gene, including exon deletions and duplications. METHODS: The authors
      performed an extensive mutational analysis on 50 probands with onset of PD at
      younger than 50 years of age. Thirteen probands were ascertained from a registry
      of familial PD and 37 probands by age at onset at younger than 50 years, blind to
      family history. Mutational analysis was undertaken on the probands and available
      family members and included conventional techniques (single strand conformation
      polymorphism analysis and sequencing) and a newly developed method of
      quantitative duplex PCR to detect alterations of gene dosage (exon deletions and
      duplications) in PARKIN: RESULTS: Using this new technique, the authors detected
      eight alterations of gene dosage in the probands, whereas 12 mutations were found
      by conventional methods among the probands and another different mutation in an
      affected family member. In total, the authors identified compound heterozygous
      mutations in 14%, heterozygous mutations in 12%, and no Parkin mutation in 74% of
      the 50 probands. We expanded the occurrence of Parkin mutations to another ethnic
      group (African-American). CONCLUSION: The authors systematically screened all 12
      Parkin exons by quantitative PCR and conventional methods in 50 probands. Eight
      mutations were newly reported, 2 of which are localized in exon 1, and 38% of the
      mutations were gene dosage alterations. These results underline the need to
      screen all exons and to undertake gene dosage studies. Furthermore, this study
      reveals a frequency of heterozygous mutation carriers that may signify a unique
      mode of inheritance and expression of the Parkin gene.

PMID- 11971095
TI  - Epilepsy, cysticercosis, and toxocariasis: a population-based case-control study
      in rural Bolivia.
AB  - OBJECTIVE: To assess the relationship between epilepsy and infection with Taenia
      solium and Toxocara canis with a case-control study, in the rural area of the
      Cordillera Province, Bolivia. METHODS: A preliminary two-phase door-to-door
      prevalence survey determined the prevalence of epilepsy and identified cases and
      control subjects. At least two control subjects per case were selected, matching
      on sex, age, and community of residence. Cases and control subjects were assessed
      serologically for antibodies against T. canis by ELISA and against T. solium by
      enzyme-linked immunoelectrotransfer blot (EITB). RESULTS: The prevalence survey
      found 130 confirmed cases of epilepsy, of which 113 were eligible for the case
      control study (59 partial seizures and 54 generalized seizures). Two hundred
      thirty-three control subjects were selected. Multivariable analysis for a matched
      case-control study was carried out. There was an association between EITB
      positivity for T. solium and epilepsy with an OR of 1.85 (95% CI 0.99 to 3.4) for
      all cases. A stronger association was found in those with partial epilepsy with a
      late onset of disease (15 years and older), where the OR was 3.66 (95% CI 1.10 to
      12.10). A positive association was also found with T. canis for all cases with an
      OR of 2.70 (95% CI 1.41 to 5.19). This increased for those with late-onset
      partial epilepsy to an OR of 18.22 (95% CI 2.10 to 158.10). CONCLUSION: This
      finding suggests that both neurocysticercosis and toxocariasis may in part
      explain the higher prevalence of epilepsy, particularly partial epilepsy, in
      developing countries.

PMID- 11971096
TI  - Field-specific visual-evoked potentials: identifying field defects in vigabatrin
      treated children.
AB  - OBJECTIVE: To derive a visual-evoked potential (VEP) technique for identifying
      visual field defects in children with epilepsy treated with vigabatrin and unable
      to perform perimetry. BACKGROUND: Studies have linked vigabatrin to a specific
      pattern of visual field loss. Few studies have included the pediatric population
      because of difficulties in assessing the visual field by perimetry below a
      developmental age of 9 years. METHODS: A field-specific VEP was developed with a
      central (0 degrees to 5 degrees radius) and peripheral stimulus (30 degrees to 60
      degrees radius). Stimuli consisted of black and white checks that increased in
      size with eccentricity. Checks reversed at different rates, allowing separate
      central and peripheral responses to be recorded. Five vigabatrin-treated young
      adults with field defects were identified using this stimulus. Electroretinograms
      (ERG) were recorded to examine the effects of vigabatrin on retinal function.
      Thirty-nine children aged 3 to 15 years were included in the study. Twelve
      patients were examined by both the field-specific stimulus test and perimetry.
      The diagnostic performance of the field-specific stimulus test was compared with
      that of perimetry. RESULTS: Thirty-five of 39 children complied with the field
      specific stimulus, 26 of 39 complied with the ERG, and 12 of 39 complied with
      perimetry. Using the summed amplitude of the peripheral response from O(2) and
      O(1), responses below 10 microV were deemed abnormal. The field-specific stimulus
      identified 3 of 4 abnormal perimetry results and 7 of 8 normal perimetry results,
      giving a sensitivity of 75% and a specificity of 87.5%. When comparing perimetry
      results with the ERG parameters, only the 30-Hz flicker amplitude, with a cutoff
      below 70 microV, gave a useful indication of visual field loss. CONCLUSION: Field
      specific VEP are well tolerated by children older than 2 years of age and are
      sensitive and specific in identifying vigabatrin-associated peripheral field
      defects.

PMID- 11971097
TI  - Impairment of slow inactivation as a common mechanism for periodic paralysis in
      DIIS4-S5.
AB  - BACKGROUND: Mutations in the human skeletal muscle sodium channels are associated
      with hyperKPP, hypoKPP, paramyotonia congenita, and potassium-aggravated
      myotonia. This article describes the clinical manifestations of a patient with
      hyperKPP carrying a mutation (L689I) occurring in the linker DIIS4-S5 and its
      functional expression in a mammalian system. OBJECTIVE: To correlate the clinical
      manifestations of hyperkalemic periodic paralysis (hyperKPP) with the functional
      expression of a sodium channel mutation. METHODS: The mutation was introduced
      into a mammalian expression vector and expressed in the human embryonic kidney
      293 cells. The functional expression of the L689I and that of the wild-type
      channels was monitored using the whole cell voltage-clamp technique. RESULTS:
      There was no change in the kinetics of fast inactivation, and inactivation curves
      were indistinguishable from that of wild-type channels. However, the L689I
      mutation caused a hyperpolarizing shift in the voltage dependence of activation
      and the mutant channels showed an impaired slow inactivation process. In
      addition, the mutant channels have a larger persistent current at -40 mV where
      window current may occur. CONCLUSIONS: The L689I mutation has similar effects to
      the T704M mutation and causes hyperKPP in this family. Because both of these
      hyperKPP mutations cause episodic muscle weakness, and because patients harboring
      another mutation (I693T) also can have episodic weakness, it is hypothesized that
      mutations occurring in this region of the sodium channel may cause episodic
      weakness through an impaired slow inactivation process coupled with enhanced
      activation.

PMID- 11971098
TI  - Giant axonal neuropathy (GAN): case report and two novel mutations in the
      gigaxonin gene.
AB  - Giant axonal neuropathy (GAN) is an autosomal recessive neurologic disorder
      clinically characterized by a severe polyneuropathy, CNS abnormalities, and
      characteristic tightly curled hair. Recently, mutations in the gigaxonin gene
      have been identified as the underlying genetic defect. The authors report two
      novel mutations confirming that GAN is caused by mutations in the gigaxonin gene
      and raise the question whether some mutations may cause a mild subclinical
      neuropathy.

PMID- 11971099
TI  - Increased levels of the pro-inflammatory prostaglandin PGE2 in CSF from ALS
      patients.
AB  - Levels of the potent pro-inflammatory prostaglandin E(2) (PGE(2)) are elevated in
      postmortem spinal cords from patients with ALS, and inhibition of a key PGE(2)
      synthesizing enzyme, cylcooxygenase-2, is neuroprotective in an in vitro model of
      ALS. The authors report that 82% of the patients with ALS studied had 2 to 10
      times higher PGE(2) levels in CSF compared with normal control subjects. That
      affected areas of the CNS are inflamed in ALS supports this. CSF PGE(2)
      measurement may be useful in monitoring treatment for ALS.

PMID- 11971100
TI  - Singing paraplegia: a distinctive manifestation of a spinal dural arteriovenous
      fistula.
AB  - The unique case of a baritone with a spinal dural arteriovenous fistula (SDAVF)
      causing recurrent, acute paraplegia during singing is described. This case
      underscores the presence of impaired venous drainage in these lesions and the
      high level of clinical suspicion required for their diagnosis in patients with
      any myelopathy.

PMID- 11971102
TI  - Spontaneous intracranial hypotension causing reversible frontotemporal dementia.
AB  - Spontaneous intracranial hypotension (SIH) causes postural headache and
      neurologic symptoms owing to traction and brain compression. A 66-year-old man
      with chronic headache and progressive personality and behavioral changes typical
      of frontotemporal dementia was examined. He had MRI findings of SIH with low CSF
      pressure. His headache, dementia, and imaging abnormalities abated after
      treatment with prednisone. SIH can cause reversible frontotemporal dementia, and
      should be considered when dementia and behavioral changes are accompanied by
      headache.

PMID- 11971101
TI  - Exercise-induced muscle "burning," fatigue, and hyper-CKemia: mtDNA T10010C
      mutation in tRNA(Gly).
AB  - A 42-year-old woman presented with myopathy and without a family history of
      neuromuscular disorder. Muscle biopsy showed ragged red fibers and reduced
      activities of mitochondrial respiratory chain enzyme complexes I, III, and IV.
      Analysis of mitochondrial DNA revealed a heteroplasmic T10010C mutation in the
      transfer RNA glycine gene.

PMID- 11971103
TI  - Improved executive functioning following repetitive transcranial magnetic
      stimulation.
AB  - The cognitive effects of active and sham repetitive transcranial magnetic
      stimulation (rTMS) were examined in 19 middle-aged and elderly patients with
      refractory depression. Patients received either active (n = 9) or sham (n = 10)
      rTMS targeted at the anterior portion of the left middle frontal gyrus. Patients
      in the active rTMS group improved significantly on a test of cognitive
      flexibility and conceptual tracking (Trail Making Test-B).

PMID- 11971104
TI  - Bilateral motor cortex output with intended unimanual contraction in congenital
      mirror movements.
AB  - In congenital mirror movements (MM), it is unclear whether the "mirror" motor
      cortex (M1) produces output during intended unimanual movements. In two patients
      with MM, the cortical silent period (CSP) was abnormally short after focal
      transcranial magnetic stimulation (TMS) of either M1, but simultaneous bilateral
      TMS led to significant CSP lengthening. Thus, it is likely that the shortened CSP
      after unilateral TMS is caused by output from the nonstimulated M1, suggesting
      that both M1 produce output with intended unimanual movements in patients with
      MM.

PMID- 11971105
TI  - Quantitative functional measures in MS: what is a reliable change?
AB  - As a first step toward understanding which changes should be considered as
      meaningful, the authors assessed the reliability of quantitative functional tests
      on 5 consecutive days in 63 patients with MS, determining the range of
      measurement variability present when patients are clinically stable. Time to walk
      25 feet (T25FW) and the 9-hole peg test (9HPT) varied by <20% of individual mean
      scores on repeated testing. Therefore, a 20% change on these tests can be
      considered to be the threshold that reliably indicates a true change in function
      for an individual.

PMID- 11971106
TI  - Anterior commissure absence without callosal agenesis: a new brain malformation.
AB  - The authors report a novel human brain malformation characterized by the absence
      of the anterior commissure without callosal agenesis, but associated with gross
      unilateral panhemispheric malformation incorporating subependymal heterotopia,
      subcortical heterotopia, and gyral abnormalities including temporal malformation
      and polymicrogyria. In contrast, a normal anterior commissure was found in 125
      control subjects and in 113 other subjects with a range of brain malformations.

PMID- 11971107
TI  - Paroxysmal episodic central thermoregulatory failure.
AB  - A 51-year-old man presenting with paroxysmal attacks of unilateral sweating for 1
      year was studied. Clinical and laboratory findings made the diagnosis of Shapiro
      or Harlequin syndrome unlikely. The onset of the sweating "crisis" was
      immediately followed by a progressive decrease in rectal and skin temperature,
      lasting for about 2 hours. This indicated that hypothermia was related to an
      abnormal downward shift of the thermoregulatory set point and a delayed effect of
      mechanisms blocking heat dissipation.

PMID- 11971108
TI  - "Shiatsu sympathectomy": ICA dissection associated with a shiatsu massager.
AB  - Carotid dissection is a well-described complication of head and neck trauma. Two
      cases of carotid dissection that occurred after use of shiatsu-type massagers are
      described. This potential cause should be considered when evaluating patients
      with idiopathic carotid dissection.

PMID- 11971109
TI  - Handheld cellular telephones and risk of acoustic neuroma.
AB  - The hypothesis that intracranial energy deposition from handheld cellular
      telephones causes acoustic neuroma was tested in an epidemiologic study of 90
      patients and 86 control subjects. The relative risk was 0.9 (p = 0.07) and did
      not vary significantly by the frequency, duration, and lifetime hours of use. In
      patients who used cellular telephones, the tumor occurred more often on the
      contralateral than ipsilateral side of the head. Further efforts should focus on
      potentially longer induction periods.

PMID- 11971110
TI  - SUNCT syndrome: prolonged attacks, refractoriness and response to topiramate.

PMID- 11971111
TI  - Hyperperfusion with vasogenic leakage by fMRI in migraine with prolonged aura.

PMID- 11971112
TI  - Results of radiotherapy for drooling in amyotrophic lateral sclerosis.

PMID- 11971113
TI  - Etoposide for recurrent spinal cord ependymoma.

PMID- 11971115
TI  - The frequency of carpal tunnel syndrome in computer users at a medical facility.

PMID- 11971116
TI  - Proposed diagnostic criteria for neurocysticercosis.

PMID- 11971117
TI  - Neuromuscular transmission in migraine: a single-fiber EMG study in clinical
      subgroups.

PMID- 11971118
TI  - Remission of intractable partial epilepsy following implantation of intracranial
      electrodes.

PMID- 11971119
TI  - Comparison of apraxia in corticobasal degeneration and progressive supranuclear
      palsy.

PMID- 11971120
TI  - Practical issues in the management of multiple sclerosis. Introduction.

PMID- 11971121
TI  - Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis.
AB  - MS is an immunologically mediated disease, as determined by observation of the
      response to immunotherapy and the existence of an animal model, experimental
      autoimmune encephalitis. Interferon (IFN) beta-1b, IFN beta-1a, and glatiramer
      acetate, the therapies used for relapsing or remitting MS, have mechanisms of
      action that address the immunologic pathophysiology of MS. The IFNs bind to cell
      surface-specific receptors, initiating a cascade of signaling pathways that end
      with the secretion of antiviral, antiproliferative, and immunomodulatory gene
      products. Glatiramer acetate, a synthetic molecule, inhibits the activation of
      myelin basic protein-reactive T cells and induces a T-cell repertoire
      characterized by anti-inflammatory effects. Although the two classes of drugs
      have some overlapping mechanisms of action, the IFNs rapidly block blood-brain
      barrier leakage and gadolinium (Gd) enhancement within 2 weeks, whereas
      glatiramer acetate produces less rapid resolution of Gd-enhanced MRI activity.
      IFN beta has no direct effects in the CNS, but glatiramer acetate-specific T
      cells are believed to have access to the CNS, where they can exert anti
      inflammatory and possibly neuroprotective effects.

PMID- 11971122
TI  - Considerations in the treatment of relapsing-remitting multiple sclerosis.
AB  - Disease-modifying drugs are available in the United States for the treatment of
      relapsing-remitting multiple sclerosis (RRMS), including interferon (IFN) beta
      1a, IFNbeta-1b, and glatiramer acetate. Another formulation of IFNbeta-1a is
      available in Europe, Canada, and other countries. Mitoxantrone is also indicated
      for the treatment of worsening forms of RRMS and secondary progressive (SP) MS.
      In addition to reductions in annual relapse rates and other measures of clinical
      disability, the disease-modifying drugs appear to reduce MRI measures of disease
      activity. Available data suggest that the efficacy of disease-modifying therapy
      is sustained for at least for 4 to 6 years. Results of clinical drug trials have
      been used as a rationale to support treatment of early MS with a disease
      modifying drug. Other medical therapies are used in the management of RRMS,
      including treatments to help manage MS-related symptoms such as spasticity and
      bladder dysfunction, and corticosteroids to hasten recovery from acute relapses.
      In some situations, interventions are used to minimize side effects of disease
      modifying drug therapy. Several currently marketed treatments, including IV
      immunoglobulin, methotrexate, and azathioprine, are being evaluated as treatments
      for RRMS in combination with the approved therapies. Investigational compounds,
      including oral formulations of glatiramer acetate and interferon, are in various
      stages of development.

PMID- 11971123
TI  - MRI in the diagnosis and management of multiple sclerosis.
AB  - MRI techniques, including conventional T(2)-weighted and gadolinium (Gd)-enhanced
      T(1)-weighted images, have provided important insights into the pathophysiology
      of MS. Although the correlation of MRI measures with clinical disability and
      outcome continues to be investigated, MRI measures are routinely used both in
      clinical practice and in MS research. In addition to its use as a diagnostic
      tool, MRI is used as a surrogate marker to monitor disease progression and
      response to therapy. A variety of MRI measures are used in drug development
      studies and have aided our understanding of the potential benefits and possible
      mechanisms of action of drug therapies. Advances in MRI techniques may further
      elucidate the pathology of MS, thus providing opportunities for new treatment
      strategies.

PMID- 11971124
TI  - Symptomatic therapy for underrecognized manifestations of multiple sclerosis.
AB  - The symptoms that affect individuals with MS are diverse and change over time.
      Addressing symptoms in a multidisciplinary fashion and helping patients address
      problems as they occur are the major elements of symptom management. Successful
      management involves treating not only the more readily recognized manifestations
      of MS but also the less apparent MS features, including fatigue, cognitive loss,
      mood disturbance, and pain. Management of these symptoms is reviewed.

PMID- 11971125
TI  - Randomized controlled trials to assess therapies for multiple sclerosis.
AB  - MS poses formidable challenges to clinical investigators. Obstacles to the study
      of MS therapies include disease chronicity, an unpredictable clinical course,
      radiologic and pathologic heterogeneity, and limited understanding of the
      underlying pathophysiology. Randomized controlled trials (RCTs) provide a means
      to assess therapeutic efficacy while reducing the risks of study bias and
      confounding factors that influence interpretation of results. RCTs have
      demonstrated that type 1 interferons and glatiramer acetate alter the short-term
      natural history of MS and have served as the basis of approval for the marketing
      of these treatments. Improvements and optimization of trial methodology may
      hasten the discovery of effective therapies and facilitate better comparisons of
      the results of individual drug trials. The most urgent need is for improved
      surrogate end points for clinical outcome with predictive validity for long-term
      disability. Even if RCT methodology is optimal, however, several limitations
      inherent to MS trials threaten to impede further progress, including obstacles to
      long-term studies (e.g., costs), patient withdrawal, and escalating sample size
      requirements to detect partial therapeutic benefit. There is a crucial need to
      develop alternative investigative methods, possibly through enhanced
      collaboration across centers and with industry, and by exploring innovative
      techniques to use existing RCT and natural history databases to greater
      advantage.

PMID- 11971126
TI  - Optimizing epilepsy management: seizure control, reduction, tolerability, and co
      morbidities. Introduction.

PMID- 11971127
TI  - Staged approach to epilepsy management.
AB  - The natural history of treated epilepsy has substantial relevance to its
      pharmacologic and surgical management. In our center, 525 unselected, untreated
      patients were given a diagnosis of epilepsy, started on antiepileptic drug (AED)
      therapy, and followed for a median of 5 years. Sixty-three percent of patients
      had been seizure-free for at least the previous year. Forty-seven percent of 470
      previously drug-naive patients responded to their first AED. Thirteen percent
      were seizure-free on the second AED, and 1% on the third monotherapy choice. Only
      3% were controlled with two AEDs and none with three. The prognosis for patients
      whose epilepsy did not respond to the first AED was strongly associated with the
      reason for failure. Only 11% of patients with inadequate control on the first AED
      later became seizure-free. These results suggest that patients with newly
      diagnosed epilepsy comprise two distinct populations. Around 60% will be
      controlled on monotherapy, usually with the first or second AED chosen. The
      remaining 30 to 40% will be difficult to control from the outset. A management
      plan should be formulated for each patient when treatment is started. Strategies
      for combining drugs should involve individual assessment of patient-related
      factors, including seizure type and epilepsy syndrome classification, combined
      with an understanding of the mechanisms of action, side effects, and interactions
      of the AEDs. Epilepsy surgery should be considered after failure of two well
      tolerated treatment regimens, whether as monotherapy or with one monotherapy and
      the first combination. Prevention of refractory epilepsy should be the goal of
      treatment when the first AED is prescribed. A staged approach to the
      pharmacologic management and, when appropriate, surgical work-up for each
      epilepsy syndrome will optimize the chance of perfect seizure control and help
      more patients achieve a fulfilling life.

PMID- 11971128
TI  - Optimizing health outcomes in active epilepsy.
AB  - Article abstract Epilepsy is a chronic condition with complex effects on a
      person's social, vocational, and psychological function. Recent advances in
      methods and instruments to assess subjective health status and patient
      preferences have provided important data on health outcomes in epilepsy. For many
      patients that do not respond to initial trials of antiepileptic medications,
      epilepsy surgery is a treatment alternative that offers the possibility of
      complete control of seizures and improved quality of life. Adverse medication
      effects and depression are readily identified by systematic use of reliable and
      valid instruments, and may be the most important negative influences on a
      person's perception of their current health status. Adequate education regarding
      relative risks of recurrent seizures compared to surgery, systematic screening
      for adverse medication effects and subsequent selection of appropriate
      antiepileptic drugs, and identification and treatment of depression should offer
      substantial improvement in overall health of persons with epilepsy.

PMID- 11971129
TI  - Cognitive outcomes and predictive factors in epilepsy.
AB  - Although most patients with epilepsy have normal cognitive abilities, they are at
      increased risk for cognitive deficits. Multiple factors contribute to this risk
      including antiepileptic drugs (AEDs), which not only reduce neuronal irritability
      but may also impair neuronal excitability. The major cognitive effects of AEDs
      are impaired attention, vigilance, and psychomotor speed, but secondary effects
      on other cognitive functions can be seen. The adverse cognitive effects of AEDs
      are offset in part by reduced seizures. In general, the cognitive effects of AEDs
      are less than the sum total of other factors, but because AEDs are the major
      therapeutic modality for epilepsy, they are of special concern. AED-induced
      cognitive side effects are increased with rapid initiation, higher dosages, and
      polytherapy. Differential cognitive effects can be seen (e.g., worse performance
      on phenobarbital), but the magnitude of cognitive effects is relatively modest
      effects for most AEDs. However, even this modest effect can be clinically
      significant and impact the patient's quality of life. In addition, some patient
      groups may be at particular risk (e.g., elderly, children, fetus). The ultimate
      therapeutic goal is to control seizures with no or minimal side effects. The
      cognitive profile of an AED is but one factor in the selection of therapeutic
      options. Ongoing seizures can be detrimental to both cognition and quality of
      life. Patients who are refractory or intolerant to AED therapy should be referred
      for video EEG monitoring to confirm the seizure diagnosis and determine if the
      patient is a candidate for epilepsy surgery.

PMID- 11971130
TI  - Depression and epilepsy: how closely related are they?
AB  - Article abstract Depressive disorders (DDs) are the most common type of
      psychiatric co-morbidity in patients with epilepsy. They are more likely to occur
      in patients with partial seizure disorders of temporal and frontal lobe origin
      and are more frequent among patients with poorly controlled seizures. Despite
      their relatively high prevalence, DDs remain unrecognized and untreated in a
      large proportion of patients. This article highlights the evidence of a close
      association between DDs and epilepsy, beginning with the bi-directional
      relationship between the two disorders. Not only are patients with epilepsy more
      likely to experience a DD, but a history of DD preceding the onset of the seizure
      disorder is more likely to be identified in patients with epilepsy than in a
      control group. In support of these observations, we review data from animal
      models of epilepsy showing that decreased activity of serotonin, norepinephrine,
      dopamine, and GABA facilitate the kindling process of seizure foci, worsen
      seizure frequency and severity, and are reversed or blocked by antidepressant
      drugs. Decreased activity of these neurotransmitters is a pivotal pathogenic
      mechanism of DDs and forms the basis of their pharmacotherapy. Thus, DDs and
      epilepsy may share common pathogenic mechanisms that facilitate the occurrence of
      one in the presence of the other. Contrary to long-held beliefs by patients and
      clinicians alike, in the sense that DDs are a "normal reaction" to the obstacles
      posed by epilepsy, we review evidence that points to their biologic or endogenous
      nature. We find a genetic predisposition to DDs, as evidenced by the frequent
      family history of mood disorders in these patients. Neuroimaging and
      neuropsychological data support a frontal lobe dysfunction in DDs, and a recent
      study documents concomitant dysfunction of mesial temporal structures. Depressive
      disorders have various clinical presentations, some typical of the different
      types of mood disorders in non-epileptic patients, others constituting rather
      frequent atypical presentations that can easily go unrecognized. A review of the
      pharmacologic treatment of DDs in epilepsy highlights the lack of scientific data
      and points to the empirical form in which these patients have been treated up to
      the present time. Contrary to clinicians' fears, most antidepressant drugs are
      safe in patients with epilepsy.

PMID- 11971131
TI  - Alternative splicing and the control of flowering time.

PMID- 11971132
TI  - Synthetic plant promoters containing defined regulatory elements provide novel
      insights into pathogen- and wound-induced signaling.
AB  - Pathogen-inducible plant promoters contain multiple cis-acting elements, only
      some of which may contribute to pathogen inducibility. Therefore, we made defined
      synthetic promoters containing tetramers of only a single type of element and
      present evidence that a range of cis-acting elements (boxes W1, W2, GCC, JERE, S,
      Gst1, and D) can mediate local gene expression in planta after pathogen attack.
      The expression patterns of the promoters were monitored during interactions with
      a number of pathogens, including compatible, incompatible, and nonhost
      interactions. Interestingly, there were major differences in the inducibilities
      of the various promoters with the pathogens tested as well as differences in the
      speed of induction and in the basal expression levels. We also show that defense
      signaling is largely conserved across species boundaries at the cis-acting
      element level. Many of these promoters also direct local wound-induced
      expression, and this provides evidence for the convergence of resistance gene,
      nonhost, and wound responses at the level of the promoter elements. We have used
      these cis-acting elements to construct improved synthetic promoters and show the
      effects of varying the number, order, and spacing of such elements. These
      promoters are valuable additions to the study of signaling and transcriptional
      activation during plant-pathogen interactions.

PMID- 11971133
TI  - The Arabidopsis Rop2 GTPase is a positive regulator of both root hair initiation
      and tip growth.
AB  - Root hairs provide a model system for the study of cell polarity. We examined the
      possibility that one or more members of the distinct plant subfamily of RHO
      monomeric GTPases, termed Rop, may function as molecular switches regulating root
      hair growth. Specific Rops are known to control polar growth in pollen tubes.
      Overexpressing Rop2 (Rop2 OX) resulted in a strong root hair phenotype, whereas
      overexpressing Rop7 appeared to inhibit root hair tip growth. Overexpressing Rops
      from other phylogenetic subgroups of Rop did not give a root hair phenotype. We
      confirmed that Rop2 was expressed throughout hair development. Rop2 OX and
      constitutively active GTP-bound rop2 (CA-rop2) led to additional and misplaced
      hairs on the cell surface as well as longer hairs. Furthermore, CA-rop2
      depolarized root hair tip growth, whereas Rop2 OX resulted in hairs with multiple
      tips. Dominant negative GDP-bound Rop2 reduced the number of hair-forming sites
      and led to shorter and wavy hairs. Green fluorescent protein-Rop2 localized to
      the future site of hair formation well before swelling formation and to the tip
      throughout hair development. We conclude that the Arabidopsis Rop2 GTPase acts as
      a positive regulatory switch in the earliest visible stage in hair development,
      swelling formation, and in tip growth.

PMID- 11971134
TI  - The ROP2 GTPase controls the formation of cortical fine F-actin and the early
      phase of directional cell expansion during Arabidopsis organogenesis.
AB  - Polar cell expansion in differentiating tissues is critical for the development
      and morphogenesis of plant organs and is modulated by hormonal and developmental
      signals, yet little is known about signaling in this fundamental process in
      plants. In contrast to tip-growing cells, such as pollen tubes and root hairs,
      cells in developing tissues are thought to expand by diffuse growth. In this
      study, we provide evidence that these cells expand in two phases with distinct
      mechanisms. In the early phase, cell expansion can occur in both longitudinal and
      radial or lateral directions and is mediated by Rop GTPase signaling, a mechanism
      known to control tip growth. The expression of a dominant-negative mutant for
      ROP2 (DN-rop2) inhibited polar cell expansion, whereas the expression of a
      constitutively active mutant (CA-rop2) caused isotropic expansion in the early
      phase. In the late phase, expansion occurs only in the longitudinal direction and
      is not affected by DN-rop2 or CA-rop2 expression. The transition from the early
      to the late phase coincides with the reorientation of cortical microtubules from
      random to transverse arrangements. Thus, cell expansion in the late phase is
      consistent with polar diffuse growth, in which polarity probably is defined by
      transverse cortical microtubules. We show that the direction of cell expansion in
      the early phase is associated with the localization of diffuse fine cortical F
      actin in leaf epidermal cells. DN-rop2 expression specifically inhibited the
      formation of this F-actin, but not actin cables, whereas CA-rop2 expression
      caused delocalized distribution of this fine F-actin throughout the cell cortex.
      Furthermore, green fluorescent protein-ROP2 was localized preferentially to the
      cortical region of the cell, where expansion apparently occurs. These
      observations suggest that ROP2 control of the polar expansion of cells within
      tissues is analogous to the Rop control of tip growth and of tip-localized F
      actin in pollen tubes and root hairs and that the tip growth mechanism also may
      modulate polar cell expansion in differentiating tissues.

PMID- 11971135
TI  - Rice TATA binding protein interacts functionally with transcription factor IIB
      and the RF2a bZIP transcriptional activator in an enhanced plant in vitro
      transcription system.
AB  - TATA binding protein (TBP) and transcription factor IIB (TFIIB) are key factors
      for the assembly of eukaryotic transcription initiation complexes. We used a rice
      whole-cell extract in vitro transcription system to characterize the functional
      interactions of recombinant plant TBP and TFIIB. Bacterially expressed rice TBP
      (OsTBP2) bound to the TATA box of the rice pal gene encoding phenylalanine
      ammonia-lyase, caused DNA bending, and enhanced basal transcription from the pal
      promoter in a TATA box-dependent manner. Recombinant rice TFIIB (OsTFIIB)
      stimulated the DNA binding and bending activities of OsTBP2 and synergistically
      enhanced OsTBP2-mediated transcription from the pal promoter and the promoter of
      Rice tungro bacilliform virus but not from the barley pr1 promoter. We also
      demonstrate a physical interaction between OsTBP2 and RF2a, a rice bZIP
      transcription factor that bound to the box II cis element of the promoter of Rice
      tungro bacilliform virus, resulting in enhanced transcription from the viral
      promoter. Enhancement of rice whole-cell extracts with recombinant transcription
      factors thus provides a powerful tool for the in vitro determination of plant
      gene regulation mechanisms. We conclude that OsTBP2 undergoes promoter-specific
      functional interactions with both the basal transcription factor OsTFIIB and the
      accessory transcription factor RF2a.

PMID- 11971136
TI  - A gene encoding an acyl hydrolase is involved in leaf senescence in Arabidopsis.
AB  - SAG101, a leaf senescence-associated gene, was cloned from an Arabidopsis leaf
      senescence enhancer trap line and functionally characterized. Reporter gene and
      RNA gel blot analyses revealed that SAG101 was not expressed until the onset of
      senescence in leaves. A recombinant SAG101 fusion protein overexpressed in
      Escherichia coli displayed acyl hydrolase activity. Antisense RNA interference in
      transgenic plants delayed the onset of leaf senescence for approximately 4 days.
      Chemically induced overexpression of SAG101 caused precocious senescence in both
      attached and detached leaves of transgenic Arabidopsis plants. These data suggest
      that SAG101 plays a significant role in leaf senescence.

PMID- 11971137
TI  - Tomato transcription factors pti4, pti5, and pti6 activate defense responses when
      expressed in Arabidopsis.
AB  - The Pti4, Pti5, and Pti6 proteins from tomato were identified based on their
      interaction with the product of the Pto disease resistance gene, a Ser-Thr
      protein kinase. They belong to the ethylene-response factor (ERF) family of plant
      unique transcription factors and bind specifically to the GCC-box cis element
      present in the promoters of many pathogenesis-related (PR) genes. Here, we show
      that these tomato ERFs are localized to the nucleus and function in vivo as
      transcription activators that regulate the expression of GCC box-containing PR
      genes. Expression of Pti4, Pti5, or Pti6 in Arabidopsis activated the expression
      of the salicylic acid-regulated genes PR1 and PR2. Expression of jasmonic acid-
      and ethylene-regulated genes, such as PR3, PR4, PDF1.2, and Thi2.1, was affected
      differently by each of the three tomato ERFs, with Arabidopsis-Pti4 plants having
      very high levels of PDF1.2 transcripts. Exogenous application of salicylic acid
      to Arabidopsis-Pti4 plants suppressed the increased expression of PDF1.2 but
      further stimulated PR1 expression. Arabidopsis plants expressing Pti4 displayed
      increased resistance to the fungal pathogen Erysiphe orontii and increased
      tolerance to the bacterial pathogen Pseudomonas syringae pv tomato. These results
      indicate that Pti4, Pti5, and Pti6 activate the expression of a wide array of PR
      genes and play important and distinct roles in plant defense.

PMID- 11971138
TI  - The Arabidopsis TONNEAU2 gene encodes a putative novel protein phosphatase 2A
      regulatory subunit essential for the control of the cortical cytoskeleton.
AB  - In Arabidopsis ton2 mutants, abnormalities of the cortical microtubular
      cytoskeleton, such as disorganization of the interphase microtubule array and
      lack of the preprophase band before mitosis, markedly affect cell shape and
      arrangement as well as overall plant morphology. We present the molecular
      isolation of the TON2 gene, which is highly conserved in higher plants and has a
      vertebrate homolog of unknown function. It encodes a protein similar in its C
      terminal part to B" regulatory subunits of type 2A protein phosphatases (PP2As).
      We show that the TON2 protein interacts with an Arabidopsis type A subunit of
      PP2A in the yeast two-hybrid system and thus likely defines a novel subclass of
      PP2A subunits that are possibly involved in the control of cytoskeletal
      structures in plants.

PMID- 11971139
TI  - A novel superfamily of transporters for allantoin and other oxo derivatives of
      nitrogen heterocyclic compounds in Arabidopsis.
AB  - A wide spectrum of soil heterocyclic nitrogen compounds are potential nutrients
      for plants. Here, it is shown that Arabidopsis plants are able to use allantoin
      as sole nitrogen source. By functional complementation of a yeast mutant
      defective in allantoin uptake, an Arabidopsis transporter, AtUPS1 (Arabidopsis
      thaliana ureide permease 1), was identified. AtUPS1 belongs to a novel
      superfamily of plant membrane proteins with five open reading frames in
      Arabidopsis (identity, 64 to 82%). UPS proteins have 10 putative transmembrane
      domains with a large cytosolic central domain containing a "Walker A" motif.
      Transport of (14)C-labeled allantoin by AtUPS1 in yeast exhibited saturation
      kinetics (K(m) approximately 52 microM), was dependent on Glc and a proton
      gradient, and was stimulated by acidic pH. AtUPS1 transports uric acid and
      xanthine, besides allantoin, but not adenine. Protons are cosubstrates in
      allantoin transport by AtUPS1, as demonstrated by expression in Xenopus laevis
      oocytes. In plants, AtUPS1 gene expression was dependent on the nitrogen source.
      Therefore, AtUPS1 presumably is involved in the uptake of allantoin and other
      purine degradation products when primary sources are limiting.

PMID- 11971140
TI  - Spreading of RNA targeting and DNA methylation in RNA silencing requires
      transcription of the target gene and a putative RNA-dependent RNA polymerase.
AB  - RNA silencing is a sequence-specific RNA degradation process that follows the
      recognition of double-stranded RNA. Here, we show that virus vectors carrying
      parts of a green fluorescent protein (GFP) transgene targeted RNA silencing in
      Nicotiana benthamiana and Arabidopsis against the entire GFP RNA. These results
      indicate that there was spreading of RNA targeting from the initiator region into
      the adjacent 5' and 3' regions of the target gene. Spreading was accompanied by
      methylation of the corresponding GFP DNA. It also was dependent on transcription
      of the transgene and on the putative RNA-dependent RNA polymerase, SDE1/SGS2.
      These findings indicate that SDE1/SGS2 produces double-stranded RNA using the
      target RNA as a template. RNA silencing of ribulose-1,5-bisphosphate
      carboxylase/oxygenase and phytoene desaturase was not associated with the
      spreading of RNA targeting or DNA methylation, indicating that these endogenous
      RNAs are not templates for SDE1/SGS2.

PMID- 11971141
TI  - PIP1 plasma membrane aquaporins in tobacco: from cellular effects to function in
      plants.
AB  - The molecular functions of several aquaporins are well characterized (e.g., by
      analysis of aquaporin-expressing Xenopus oocytes). However, their significance in
      the physiology of water transport in multicellular organisms remains uncertain.
      The tobacco plasma membrane aquaporin NtAQP1 was used to elucidate this issue. By
      comparing antisense plants that were inhibited in NtAQP1 expression with control
      plants, we found evidence for NtAQP1 function in cellular and whole-plant water
      relations. The consequences of a decrease in cellular water permeability were
      determined by measurement of transpiration rate and stem and leaf water potential
      as well as growth experiments under extreme soil water depletion. Plants impaired
      in NtAQP1 expression showed reduced root hydraulic conductivity and lower water
      stress resistance. In conclusion, our results emphasize the importance of
      symplastic aquaporin-mediated water transport in whole-plant water relations.

PMID- 11971142
TI  - Functional significance of the alternative transcript processing of the
      Arabidopsis floral promoter FCA.
AB  - The Arabidopsis gene FCA encodes an RNA binding protein that functions to promote
      the floral transition. The FCA transcript is alternatively processed to yield
      four transcripts, the most abundant of which is polyadenylated within intron 3.
      We have analyzed the role of the alternative processing on the floral transition.
      The introduction of FCA intronless transgenes resulted in increased FCA protein
      levels and accelerated flowering, but no role in flowering was found for products
      of the shorter transcripts. The consequences of the alternative processing on the
      FCA expression pattern were determined using a series of translational FCA-beta
      glucuronidase fusions. The inclusion of FCA genomic sequence containing the
      alternatively processed intron 3 restricted the expression of the transgene
      predominantly to shoot and root apices and young flower buds. Expression of this
      fusion also was delayed developmentally. Therefore, the alternative processing of
      the FCA transcript limits, both spatially and temporally, the amount of
      functional FCA protein. Expression in roots prompted an analysis of root
      development, which indicated that FCA functions more generally than in the
      control of the floral transition.

PMID- 11971143
TI  - Identification and characterization of the Arabidopsis PHO1 gene involved in
      phosphate loading to the xylem.
AB  - The Arabidopsis mutant pho1 is deficient in the transfer of Pi from root
      epidermal and cortical cells to the xylem. The PHO1 gene was identified by a map
      based cloning strategy. The N-terminal half of PHO1 is mainly hydrophilic,
      whereas the C-terminal half has six potential membrane-spanning domains. PHO1
      shows no homology with any characterized solute transporter, including the family
      of H(+)-Pi cotransporters identified in plants and fungi. PHO1 shows highest
      homology with the Rcm1 mammalian receptor for xenotropic murine leukemia
      retroviruses and with the Saccharomyces cerevisiae Syg1 protein involved in the
      mating pheromone signal transduction pathway. PHO1 is expressed predominantly in
      the roots and is upregulated weakly under Pi stress. Studies with PHO1 promoter
      beta-glucuronidase constructs reveal predominant expression of the PHO1 promoter
      in the stelar cells of the root and the lower part of the hypocotyl. There also
      is beta-glucuronidase staining of endodermal cells that are adjacent to the
      protoxylem vessels. The Arabidopsis genome contains 10 additional genes showing
      homology with PHO1. Thus, PHO1 defines a novel class of proteins involved in ion
      transport in plants.

PMID- 11971144
TI  - Genome-wide analysis of core cell cycle genes in Arabidopsis.
AB  - Cyclin-dependent kinases and cyclins regulate with the help of different
      interacting proteins the progression through the eukaryotic cell cycle. A high
      quality, homology-based annotation protocol was applied to determine the core
      cell cycle genes in the recently completed Arabidopsis genome sequence. In total,
      61 genes were identified belonging to seven selected families of cell cycle
      regulators, for which 30 are new or corrections of the existing annotation. A new
      class of putative cell cycle regulators was found that probably are competitors
      of E2F/DP transcription factors, which mediate the G1-to-S progression. In
      addition, the existing nomenclature for cell cycle genes of Arabidopsis was
      updated, and the physical positions of all genes were compared with segmentally
      duplicated blocks in the genome, showing that 22 core cell cycle genes emerged
      through block duplications. This genome-wide analysis illustrates the complexity
      of the plant cell cycle machinery and provides a tool for elucidating the
      function of new family members in the future.

PMID- 11971145
TI  - A Magnaporthe grisea cyclophilin acts as a virulence determinant during plant
      infection.
AB  - Cyclophilins are peptidyl prolyl cis-trans isomerases that are highly conserved
      throughout eukaryotes and that are best known for being the cellular target of
      the immunosuppressive drug cyclosporin A (CsA). The activity of CsA is caused by
      the drug forming a complex with cyclophilin A and inhibiting the calmodulin
      dependent phosphoprotein phosphatase calcineurin. We have investigated the role
      of CYP1, a cyclophilin-encoding gene in the phytopathogenic fungus Magnaporthe
      grisea, which is the causal agent of rice blast disease. CYP1 putatively encodes
      a mitochondrial and cytosolic form of cyclophilin, and targeted gene replacement
      has shown that CYP1 acts as a virulence determinant in rice blast. Cyp1 mutants
      show reduced virulence and are impaired in associated functions, such as
      penetration peg formation and appressorium turgor generation. CYP1 cyclophilin
      also is the cellular target for CsA in Magnaporthe, and CsA was found to inhibit
      appressorium development and hyphal growth in a CYP1-dependent manner. These data
      implicate cyclophilins as virulence factors in phytopathogenic fungi and also
      provide evidence that calcineurin signaling is required for infection structure
      formation by Magnaporthe.

PMID- 11971149
TI  - Editorial.

PMID- 11971146
TI  - Genes for two mitochondrial ribosomal proteins in flowering plants are derived
      from their chloroplast or cytosolic counterparts.
AB  - Often during flowering plant evolution, ribosomal protein genes have been lost
      from the mitochondrion and transferred to the nucleus. Here, we show that
      substitution by a duplicated, divergent gene originally encoding the chloroplast
      or cytosolic ribosomal protein counterpart accounts for two missing mitochondrial
      genes in diverse angiosperms. The rps13 gene is missing from the mitochondrial
      genome of many rosids, and a transferred copy of this gene is not evident in the
      nucleus of Arabidopsis, soybean, or cotton. Instead, these rosids contain a
      divergent nuclear copy of an rps13 gene of chloroplast origin. The product of
      this gene from all three rosids was shown to be imported into isolated
      mitochondria but not into chloroplasts. The rps8 gene is missing from the
      mitochondrion and nucleus of all angiosperms examined. A divergent copy of the
      gene encoding its cytosolic counterpart (rps15A) was identified in the nucleus of
      four angiosperms and one gymnosperm. The product of this gene from Arabidopsis
      and tomato was imported successfully into mitochondria. We infer that rps13 was
      lost from the mitochondrial genome and substituted by a duplicated nuclear gene
      of chloroplast origin early in rosid evolution, whereas rps8 loss and
      substitution by a gene of nuclear/cytosolic origin occurred much earlier, in a
      common ancestor of angiosperms and gymnosperms.

PMID- 11971150
TI  - Cost-effectiveness of antidepressant medications.
AB  - BACKGROUND: Antidepressant medications have been shown to effectively relieve
      symptoms, improve interpersonal and occupational functioning and reduce
      disability from coexisting medical conditions. Although the newer selective
      serotonin reuptake inhibitors (SSRIs) have improved tolerability, are easier to
      take and are associated with longer lengths of therapy when compared with the
      tricyclic antidepressants (TCAs), the relative cost-effectiveness of alternative
      antidepressants remains unclear. AIMS OF THE STUDY: This study seeks to determine
      (i) the probability that relapse or recurrence of depression can be prevented by
      appropriate antidepressant choice, (ii) the cost associated with relapse or
      recurrence of depression and (iii) the relative cost-effectiveness of alternative
      antidepressants. METHODS: We use a quasi-experimental design to compare claims
      from a state Medicaid plan for TCA and SSRIs users. RESULTS: Premature
      discontinuation of antidepressant medication is the strongest predictor of
      relapse and recurrence. Antidepressant choice was not an independent predictor of
      relapse or recurrence. The effect of relapse and recurrence on expenditures is
      complex, with a non-significant trend toward lower expenditures for those who had
      longer periods between episodes of depression two years after initiation of
      treatment for the first episode. We were unable to replicate prior research
      results regarding the impact of SSRIs on duration of therapy in this Medicaid
      plan. CONCLUSIONS: Premature discontinuation of antidepressant treatment is
      associated with a high probability of relapse and recurrence. Health care
      expenditures are not altered by preventing relapse and recurrence. We suggest
      that antidepressant medications associated with reduced probability of premature
      discontinuation should be considered cost-effective. IMPLICATIONS FOR HEALTH CARE
      PROVISION AND USE: There are very few variables which health care providers can
      use to improve the outcomes and associated economic consequences of depression.
      Among these factors, treatment choice and adherence to the prescribed treatment
      are likely candidates. In this paper, we suggest that adherence to antidepressant
      medication results in substantial improvement in the time to relapse or
      recurrence of depression. Choice of an SSRI may thus improve treatment outcome by
      lengthening remission. In addition, this choice is not associated with higher
      costs. IMPLICATIONS FOR HEALTH POLICY FORMULATION: Depressive illnesses are
      associated with high rates of health service use and functional impairment. Thus,
      the societal burden is quite high. This paper furthers the debate regarding the
      relative cost-effectiveness of antidepressant medications, and our findings
      suggest several ways that policy makers can improve the care of depressed
      individuals at little additional cost. Specifically our findings highlight the
      importance of adherence to current recommendations regarding the length of
      antidepressant treatment and suggest several methods for improving this important
      outcome. IMPLICATIONS FOR FURTHER RESEARCH: The relative cost-effectiveness of
      alternative antidepressant medications continues to be an important and unsolved
      issue. We suggest the need for future research in this area using a variety of
      research designs appropriate to the question. The quasi-experimental approach
      outlined here seems promising in this regard.

PMID- 11971151
TI  - Interactions between use of and insurance for specialty ambulatory mental health
      services.
AB  - BACKGROUND: There is continuing interest in the effects of coinsurance rates on
      the use of ambulatory mental health services. Persons who expect to use mental
      health services may choose coverage with more generous mental health benefits, as
      such treatment may be expected to be a recurring activity. However, it may also
      be the case that if the expected need for such services is somehow reflected in
      lower perceived human capital in the labor market, then persons who have a higher
      probability of use may face a less generous set of health insurance options.
      These behaviors imply some simultaneity in the determinants of the coinsurance
      rate facing an individual and their mental health use. AIM OF THE STUDY: To
      explore the joint determination of the use of and coinsurance for ambulatory
      mental health services, using non-experimental data for a nationally
      representative sample of the non-institutionalized who had employer-based health
      insurance in the United States. METHODS: I estimate an instrument for the
      ambulatory mental health coinsurance rate. I then estimate two models of the
      demand for ambulatory mental health care as a function of the coinsurance rate
      for this type of care and other factors, one using the actual coinsurance rate
      and the other using the estimated instrument for the coinsurance rate. RESULTS:
      In the instrumental equation, an index of the mental distress of the key worker
      most likely to be the policy-holder has no statistically significant effect on
      the worker's coinsurance rate. However, a similar measure for other members of
      the worker's family has a positive and statistically significant effect on the
      worker's coinsurance rate. In the demand equations, neither the actual
      coinsurance rate nor its instrument has a statistically significant coefficient.
      DISCUSSION: Having another family member who may need mental health care results
      in some effort to seek a health plan with a higher coinsurance rate for such
      services. While the mental health index for the key worker would motivate the
      same type of seeking behavior, a higher level for this index for the key worker
      might also be correlated with a lower level of perceived human capital in a
      prospective employer's eyes, and this might result in a more restricted set of
      plan options for mental health care in the labor market. The absence of
      statistical significant for the coefficients of the actual coinsurance rate and
      its instrument also provides some limited but suggestive evidence of employer
      side selection effects. LIMITATIONS: It was not possible to model the full
      complexity of health plans. CONCLUSIONS: The discussions of selection bias with
      regard to mental health insurance and service use should be expanded to include
      demand-side effects in the labor market, in addition to the supply-side effects
      on the part of workers that are often considered. IMPLICATIONS FOR HEALTH CARE
      PROVISION AND USE: It may be difficult to determine the effects on ambulatory
      mental health care of changes in health insurance provisions. IMPLICATIONS FOR
      HEALTH POLICY FORMULATION: Caution needs to be used in making estimates of the
      effects of changes in insurance coverage for ambulatory mental health care.
      Persons who find their benefits improved may not respond at the rate expected,
      because initial coinsurance rates are already in part intertwined with expected
      use. IMPLICATIONS FOR FURTHER RESEARCH: More analyses of the range of selection
      effects in labor markets and their impacts on health insurance are warranted.

PMID- 11971147
TI  - Rab2 GTPase regulates vesicle trafficking between the endoplasmic reticulum and
      the Golgi bodies and is important to pollen tube growth.
AB  - Pollen tube elongation depends on the secretion of large amounts of membrane and
      cell wall materials at the pollen tube tip to sustain rapid growth. A large
      family of RAS-related small GTPases, Rabs or Ypts, is known to regulate both
      anterograde and retrograde trafficking of transport vesicles between different
      endomembrane compartments and the plasma membrane in mammalian and yeast cells.
      Studies on the functional roles of analogous plant proteins are emerging. We
      report here that a tobacco pollen-predominant Rab2, NtRab2, functions in the
      secretory pathway between the endoplasmic reticulum and the Golgi in elongating
      pollen tubes. Green fluorescent protein-NtRab2 fusion protein localized to the
      Golgi bodies in elongating pollen tubes. Dominant-negative mutations in NtRab2
      proteins inhibited their Golgi localization, blocked the delivery of Golgi
      resident as well as plasmalemma and secreted proteins to their normal locations,
      and inhibited pollen tube growth. On the other hand, when green fluorescent
      protein-NtRab2 was over-expressed in transiently transformed leaf protoplasts and
      epidermal cells, in which NtRab2 mRNA have not been observed to accumulate to
      detectable levels, these proteins did not target efficiently to Golgi bodies.
      Together, these observations indicate that NtRab2 is important for trafficking
      between the endoplasmic reticulum and the Golgi bodies in pollen tubes and may be
      specialized to optimally support the high secretory demands in these tip growth
      cells.

PMID- 11971152
TI  - Mental health and substance abuse parity: a case study of Ohio's state employee
      program.
AB  - BACKGROUND: In the United States, insurance benefits for treating alcohol, drug
      abuse and mental health (ADM) problems have been much more limited than medical
      care benefits. To change that situation, more than 30 states were considering
      legislation that requires equal benefits for ADM and medical care ("parity") in
      the past year. Uncertainty about the cost consequences of such proposed
      legislation remains a major stumbling block. There has been no information about
      the actual experience of implementing parity benefits under managed care or the
      effects on access to care and utilization. AIMS OF THE STUDY: Document the
      experience of the State of Ohio with adopting full parity for ADM care for its
      state employee program under managed care. Ohio provides an unusually long time
      series with seven years of managed behavioral health benefits, which allows us to
      study inflationary trends in a plan with unlimited ADM benefits. METHODS:
      Primarily a case study, we describe the implementation of the program and track
      utilization, and costs of ADM care from 1989 to 1997. We use a variety of
      administrative and claims data and reports provided by United Behavioral Health
      and the state of Ohio. The analysis of the utilization and cost effect of parity
      and managed care is pre-post, with a multiyear follow-up period. RESULTS: The
      switch from unmanaged indemnity care to managed carve-out care was followed by a
      75% drop in inpatient days and a 40% drop in outpatient visits per 1000 members,
      despite the simultaneous increase in benefits. The subsequent years saw a
      continuous decline in inpatient days and an increased use of intermediate
      services, such as residential care and intensive outpatient care. The number of
      outpatient visits stabilized in the range of 500-550 visits per 1000. There was
      no indication that costs started to increase during the study period; instead,
      costs continued to decline. A somewhat different picture emerges when comparing
      utilization under HMOs with utilization under a carve-out with expanded benefits.
      In that case, the expansion of benefits led to a significant jump in outpatient
      utilization and intermediate services, while there was a small decrease in
      inpatient days. Insurance payments in 1996/1997 were almost identical to the
      estimated costs under HMOs in 1993. CONCLUSIONS: In contrast to the emerging
      inflation anxiety regarding overall health care costs, managed care can provide
      long-run cost containment for ADM care even when patient copayments are reduced
      and coverage limits are lifted. This may differentiate ADM care from medical care
      and reasons for this difference include the state of management techniques (more
      advanced for ADM care), complexity of treatments (much higher technology
      utilization in medical care) and demographic factors (medical, but not behavioral
      health, costs increase as the population ages). IMPLICATIONS FOR HEALTH POLICY:
      The experience of the state of Ohio demonstrates that parity level benefits for
      ADM care are affordable under managed care. It suggests that the concerns about
      costs that have stymied ADM policy proposals are unfounded, as long as one is
      willing to accept managed care. IMPLICATIONS FOR RESEARCH: The continuing decline
      in costs raises concerns that levels of care may become insufficient. While
      concerns about costs being too high dominate the policy hurdle for parity
      legislation at this moment, the next step in research is to address quality of
      care or health outcomes, areas about which even less is known than about costs.

PMID- 11971153
TI  - Mental health parity: what are the gaps in coverage? 
AB  - BACKGROUND: Mental health benefits in private health insurance plans in the
      United States are typically less generous than benefits for physical health care
      services, driving reform efforts to achieve parity in coverage. While there is
      growing evidence about the effects such legislation would have on the utilization
      and cost of mental health services, less is known about the impact parity would
      have on reducing the risk of large out-of-pocket expenses that families would
      face in the event of mental illness. AIMS OF THE STUDY: We seek to understand the
      impact that mental health parity would have on the out-of-pocket burden that
      families would face in the event of mental illness. We focus in particular on
      variations in coverage across the privately insured population. METHODS: We
      compare out-of-pocket spending for hypothetical episodes of mental health
      treatment, first under current insurance coverage in the United States and then
      under a reform policy of full mental health parity. We exploit detailed
      informtion on actual health plan benefits using a nationally-representative
      sample of the privately insured population under age 65 from the 1987 National
      Medical Expenditure Survey (NMES) that has been carefully aged and reweighted to
      represent 1995 population and benefit characteristics. RESULTS: Our results show
      that existing benefits of the U.S. privately insured population under age 65
      leave most people at risk of high out-of-pocket costs in the event of a serious
      mental illness. Moreover, the generosity of existing mental health benefits
      varies widely across subgroups, particularly across firm size. We find
      significantly lower out-of-pocket costs when simulating full parity coverage.
      However, our results show those with less generous mental health coverage tend to
      have less generous physical health coverage, as well. CONCLUSIONS: Parity would
      substantially increase generosity of mental health coverage for most of the
      privately insured population. The wide variation in the generosity of existing
      mental health benefits suggests that there are likely to be differential impacts
      from a parity mandate. Those with limited physical health coverage would still be
      at significant financial risk for catastrophic mental illness.

PMID- 11971154
TI  - Helicobacter pylori vacuolating cytotoxin, VacA.
AB  - Helicobacter pylori is the leading bacterial cause of food-borne illness
      worldwide and plays a major role in the development of chronic gastritis, peptic
      ulcer, and gastric cancer. Strains isolated from patients contain the cagA gene
      (cytotoxin-associated gene A) and produce the vacuolating cytotoxin, VacA. Recent
      molecular and cellular studies of VacA action have begun to unravel its structure
      and the details of the mechanism of gastric injury caused by H. pylori infection.

PMID- 11971155
TI  - Herpesvirus infections of the central nervous system.
AB  - In recent years, advances in the diagnosis and treatment of herpes simplex
      encephalitis (HSE) have been achieved due to the prevalence of antiviral drugs
      and the introduction of the polymerase chain reaction (PCR) to test the
      cerebrospinal fluid. The several clinical forms of herpes simplex virus type 1
      (HSV-1) infections of the central nervous system (CNS), including acute
      disseminated encephalomyelitis and brainstem encephalitis, have been clarified.
      However, fatal, prolonged, or relapsed cases are still observed, and early
      detection and appropriate treatment is necessary to lead to a good prognosis for
      these intractable HSE cases. In adult HSV-2 infections, meningitis and myelitis
      associated with genital herpes are common. In the past, HSV-2 myelitis has been
      reported as a form of fatal necrotizing myelopathy; however, using PCR and
      magnetic resonance imaging studies, mild surviving cases are increasingly likely
      to be identified. Meanwhile, various CNS syndromes resulting from the herpes
      group viruses, including varicella-zoster virus and Epstein-Barr virus have also
      been reported. These herpesviruses have several characteristics in common, e.g.,
      they exist in the latent state and they occur in both mucocutaneous and CNS
      infections. Adult HSV-1 and -2 infections of the CNS are discussed together with
      other herpes group virus infections of the CNS.

PMID- 11971156
TI  - Prevalence of Escherichia coli possessing the eaeA gene of enteropathogenic E.
      coli (EPEC) or the aggR gene of enteroaggregative E. coli (EAggEC) in traveler's
      diarrhea diagnosed in those returning to Tama, Tokyo from other Asian countries.
AB  - To elucidate the importance of enteropathogenic Escherichia coli (EPEC) and
      enteroaggregative E. coli (EAggEC) as etiological agents in traveler's diarrhea,
      the detection of the eaeA and aggR gene in E. coli strains isolated from overseas
      travelers with diarrhea in Tama, Tokyo was carried out using a PCR method. Of 192
      travelers who were mostly adults and had visited Asian countries from April 1998
      to March 1999, aggR-positive E. coli strains were detected in 26 (13.5%). These
      strains represent the second predominant enteropathogen following enterotoxigenic
      E. coli (ETEC), whereas eaeA-positive E. coli strains were confirmed in seven
      subjects (3.6%). In 13 cases with aggR and four cases with eaeA, the organisms
      were detected in stool samples of patients as the only potential enteric
      pathogen. The clinical symptoms of these patients were similar to those in
      patients with ETEC; however, the severity of illness was milder than that
      associated with ETEC alone. Three strains with eaeA and five strains with aggR
      were typed as six different kinds of O serogroups, of which four strains belonged
      to the classical EPEC serogroups (O55, O114, O119, and O127a). These findings
      suggest that aggR-positive E. coli (EAggEC) is a significant causative agent in
      traveler's diarrhea. In addition, it was demonstrated that eaeA-positive E. coli
      (EPEC) is markedly correlated with diarrhea in adults.

PMID- 11971157
TI  - High genomic diversity of enterohemorrhagic Escherichia coli isolates in Japan
      and its applicability for the detection of diffuse outbreak.
AB  - Genotyping of 1,102 enterohemorrhagic Escherichia coli isolates by the use of
      pulsed-field gel electrophoresis (PFGE) carried out from January to November 2000
      has revealed the high genomic diversity of these isolates in Japan. By combining
      the results of genotyping of the isolates with the information from other
      epidemiological investigations of the cases, we identified a diffuse outbreak in
      Japan in the year 2000 that seemed to be sporadic but was actually linked.
      Isolates with only the Shiga toxin 2 gene derived from patient specimens and the
      contaminated food involved in this diffuse outbreak showed an indistinguishable
      PFGE profile and the same phage type. Based on the diversity of genotypes among
      the isolates of enterohemorrhagic E. coli O157:H7/- in Japan, we suggest the
      presence of a few other possible diffuse outbreaks due to the organisms, showing
      indistinguishable genotypes.

PMID- 11971158
TI  - Evaluation of a sentinel surveillance system for influenza, 1995-2000, Kyoto
      City, Japan.
AB  - We compared a municipal sentinel surveillance system for influenza with the
      Microbial Isolation Surveillance System (MISS) in Kyoto City, Japan. Sensitivity,
      specificity, and predictive value positive (PVP) of the Influenza Sentinel
      Surveillance System (ISSS) compared to the MISS were calculated by influenza
      season and by month. Sensitivity ranged from 80 to 97%, specificity ranged from
      55 to 77%, and PVP ranged from 29 to 52% by season (P < 0.001). On the other
      hand, sensitivity ranged from 86 to 100%, specificity ranged from 38 to 66%, and
      PVP ranged from 31 to 50% by month (P < 0.001). Specificity was calculated as 93%
      in November. The sensitivity of ISSS was found to be sufficient regardless of the
      magnitude of influenza activity. Specificity varied by season, indicating the
      difficulty of clinically diagnosing other respiratory illnesses. The PVP remained
      at less than 50% before and after the influenza seasons and it varied year by
      year. In general, the ISSS is a good surveillance system for monitoring influenza
      activity.

PMID- 11971159
TI  - Minimally invasive method for collection of blood from guinea pigs.

PMID- 11971160
TI  - Molecular epidemiology of methicillin-resistant Staphylococcus aureus in a
      Kumamoto hospital in 2001.

PMID- 11971161
TI  - A Queensland koala kept in a Japanese zoological park was carrier of an imported
      fungal pathogen, Filobasidiella neoformans var. bacillispora (Cryptococcus
      neoformans var. gattii).

PMID- 11971162
TI  - Re-evaluation of HCV Ab detection kits approved for marketing in Japan.

PMID- 11971163
TI  - [The relationship between the chromaffin granule number and the granule calcium
      content in the adrenal medulla of restrained rats].
AB  - Morphometry of numerical density and electron probe X-ray quantitative
      microanalysis were used to measure the alterations in the number and calcium
      content of chromaffin granules in adrenal medulla cells during emergency reaction
      of restrained rats. It was found that both the alterations showed monotonic
      decrease during the period of restraint, but the rate of decrease of the calcium
      content was significantly faster than that of the granules. These data are
      consistent with the hypothesis that calcium release from the granules may
      increase the cytoplasmic calcium concentration, which again triggers off the
      granule exocytosis.

PMID- 11971164
TI  - Neural control of the compensatory increase of testosterone in hemicastrated
      adult male rats.
AB  - It is unclear why the concentration of testosterone increases in the testicular
      vein after hemicastration without corresponding alteration in gonadotropins. The
      present work was undertaken to examine whether the testosterone levels could be
      modified by denervation of the testis in adult rats. Both systemic and testicular
      blood samples were collected either immediately before or 6 and 24 hours after
      hemicastration from the rats two weeks after denervation of either inferior
      spermatic nerves (ISN) or ISN plus superior spermatic nerves (ISN-SSN). Increase
      of testicular testosterone induced by hemicastration was significantly (P<0.05)
      inhibited in these rats, as compared with the sham animals (at 6 and 24 hours,
      ISN vs sham: 16.00+/-3.35 vs 42.72+/-13.85 and 26.93+/-8.68 vs 71.16+/-13.30
      whilst ISN-SSN vs sham: 31.63+/-7.92 vs 60.61+/-18.11 and 27.70+/-8.93 vs 93.92+/
      19.73 ng/ml, respectively), whereas no significant change in LH was observed in
      all the experimental groups. FSH underwent no alteration in all the ISN
      denervation groups, but a significant elevation was observed in the ISN-SSN
      denervation groups (P<0.05) before hemicastration. Therefore, it appears that the
      change in FSH is not the cause of the inhibition of testosterone increase in the
      hemicastrated rats after testicular denervation and that ISN plays an active role
      in regulation of testosterone increase induced by hemicastration.

PMID- 11971165
TI  - [Effects of c-erbB(2) on the hCG-induced progesterone production of rat luteal
      cells].
AB  - The effects of c-erbB(2) antisense oligodeoxynucleotides (antisense c-erbB(2)
      ODN) on hCG-induced progesterone production of isolated rat luteal cells in
      relation to cAMP, Ca(2+) and cycloheximide (CYX) were investigated. Antisense c
      erbB(2) ODN inhibited hCG-induced progesterone production in a dose-dependent
      manner; and the percentage of luteal cells stained for c-erbB(2) protein was
      decreased. But nonsense tat ODN had no similar effect. The effect of dbcAMP was
      in contrast with that of antisense c-erbB(2) ODN, which suppressed the
      progesterone production and reduced the percentage of luteal cells stained for c
      erbB(2) protein. On the other hand, both verapamil and CYX enhanced the
      inhibition of antisense c-erbB(2) ODN. The result of the present investigation
      suggests that cAMP, Ca(2+)-dependent pathway participates in the expression of
      protooncogene.

PMID- 11971166
TI  - [Cell activities in primate areas F2 and F4 of the monkey during sequential motor
      task guided by recognition of figures].
AB  - Single-unit activities were recorded in the area F2 of dorsal premotor cortex
      (PMd) and area F4 of ventral premotor cortex (PMv) while a monkey was performing
      a sequential motor task guided by recognition of figures (FRS). During the cue
      period, 52% (39/75) and 16.9% (13/77) of the task-related neurons exhibited
      changes in activities in the areas F2 and F4, respectively. During the touch
      period, 51% (38/75) and 87% (67/77) of the task-related neurons exhibited changes
      in activities in the areas F2 and F4, respectively. There were more cells
      responding to the cue signal in F2 than in F4 (X(2)  20.8, P<0.005). In contrast,
      there were more cells responding during the touch period in F4 than in F2 (X(2) 
      23.5, P<0.005). The present findings indicate that a lot of neurons in the PMd
      and PMv are differently involved in the FRS task.

PMID- 11971167
TI  - Effect of intracerebralventricular injection of nitric oxide donor and nitric
      oxide synthase inhibitor on the spontaneous discharge of magnocellular neurons of
      paraventricular nucleus in the rat.
AB  - The effects of intracerebralventricular (icv) injection of nitric oxide (NO)
      donor and nitric oxide synthase (NOS) inhibitor on the spontaneous discharge of
      magnocellular neurons of paraventricular nucleus (PVN) of hypothalamus were
      investigated in urethane anaesthetized adult SD rats by using microelectrode
      extracellularly recording method. The results showed that icv injection of NO
      donor sodium nitroprusside (SNP) had dose-dependent inhibitory effects on
      vasopressin (VP) secreting units in PVN. Icv injection of NOS inhibitor N(  )
      nitro-L-arginine methyl ester (L-NAME) also inhibited all of the VP-secreting
      neurons examined. Both the drugs had no effect on almost all oxytocin (OT)
      secreting units. These results suggest that NO may differentially modulate the
      activities of OT and VP neurons.

PMID- 11971168
TI  - [Cardiocyte hypertrophy induced by cultured neonatal rat ventricular fibroblast
      conditioned growth medium].
AB  - The present work demonstrated that cultured neonatal rat ventricular fibroblast
      conditioned growth medium (FCGM) could significantly increase cell surface area
      and protein content and promote  (3)H  -Leucine incorporation on neonatal rat
      cardiomyocyte. The above effect was strongest on the third day, and was dose
      dependent. BQ(123), an ET-A receptor antagonist, significantly blocked the
      effect, while CV11974, an Ang II I-type receptor antagonist, and regitin, an
      alpha-adrenergic receptor antagonist, did not. These results suggest that there
      are some substances promoting hypertrophy of cardiomyocytes in FCGM, which may be
      ET-1. The FCGM-induced increases in cardiomyocyte protein synthesis and cell
      surface area were inhibited partially by pertusis toxin (PTX) and PKC inhibitor
      staurosporine (ST), suggesting that the hypertrophic effect is related with PTX
      sensitive G protein and PKC.

PMID- 11971169
TI  - [Relation between myocardial cAMP and renin-angiotensin system activation after
      acute pressure overload].
AB  - In order to investigate the relationship between cAMP and myocardial renin
      angiotensin system activation after acute pressure overload, an animal model of
      acute pressure overload was established by constriction of abdominal aorta. It
      was found that angiotensin converting enzyme (ACE) mRNA and protein expression
      were increased markedly, ACE activity and angiotensin II content were also
      elevated significantly in rat heart 1 h after acute pressure overload, and the
      increases were kept at high level. Meanwhile the myocardial cAMP concentration
      was increased significantly at 0.5 h, reached the peak at day 5, and returned to
      normal at day 30 after operation. Then cardiomyocytes were cultured to observe
      whether ACE gene expression can be induced by cAMP. The results showed that
      elevation of cAMP content in cultured cardiomyocytes stimulated by isoproterenol
      (ISO, 0.01 micromol/L) increased ACE mRNA and protein expression, and also
      increased ACE activity and Ang II content in cultural medium. These results
      suggest that cAMP plays a role in the mechanism of activation of myocardial renin
      angiotensin system induced by pressure overload.

PMID- 11971170
TI  - [The effects of cytokines produced by bone marrow endothelial cells on the
      regulation of hematopoiesis].
AB  - In this study, the effects of bone marrow endothelial cell conditioned medium
      (BMEC-CM) on hematopoietic progenitors and the expression of cytokines mRNA of
      BMEC were investigated. BMEC-CM was ultrafiltrated in Centriprep-10, an
      ultrafiltering concentrator. The retentate (MW>10 kD) and filtrate (MW<10 kD)
      were obtained. The effects of different components of BMEC-CM on the murine
      hematopoietic progenitors were examined. The results showed that the retentate of
      BMEC-CM (MW>10 kD) significantly promoted the growth of CFU-GM, CFU-E, BFU-E, CFU
      Meg and HPP-CFC, while the growth of CFU-GM, CFU-E, BFU-E, CFU-Meg and HPP-CFC
      were markedly inhibited by the filtrate of BMEC-CM (MW<10 kD). The effects of
      BMEC-CM were dose-dependent. The presence of mRNAs for GM-CSF, TGF-beta, bone
      morphogenetic protein 2A, basic fibroblast growth factor receptor, endothelin-2,
      macrophage-stimulating 1 (MSP-1), thymosin-beta10, connective tissue growth
      factor, macrophage inflammatory protein 2 alpha (MIP-2alpha), IL-6, IL-11, IL-13
      and IFN-gamma mRNA were successfully detected by Atlas Arrays.

PMID- 11971171
TI  - [Blocking effects of extracellular Ba(2+) on the inward rectifier potassium
      channel].
AB  - Two-microelectrode voltage clamp (TEV) method was used to study the blocking
      effects of extracellular Ba(2+) on the inward rectifier potassium channel (IRK1)
      expressed in Xenopus oocytes. Blockage of Ba(2+) on IRK1 (1 ms after voltage
      applied) is Ba(2+) concentration (0,1,3,10 or 100 micromol/L) dependent with 10
      or 90 mmol/L potassium and also voltage-dependent. Ba(2+) almost has no effect on
      the open/close of IRK1. IRK1 is not permeable to Ba(2+). Three exponential
      fitting analysis indicates that Ba(2+) and K(+) compete the same binding site in
      IRK1 when external Ba(2+) concentration is lower (1 or 3 micromol/L). The time
      constant of IRK1 does not increase, but the concentration dependency of the
      weights of the fittings increases with the increase of external Ba(2+)
      concentration. As a result, the inactivation becomes faster and faster as the
      external Ba(2+) concentration increases. Moreover, since the time constant of the
      channel decreases and the weights of the fittings concentration dependently
      increase with the increase of external Ba(2+) concentration (10 or 100
      micromol/L), the inactivation becomes faster and faster. It is demonstrated that
      Ba(2+) can contact with deeper binding sites in IRK1 as external Ba(2+)
      concentration increases. It is suggested that two different mechanisms may
      underlie the external Ba(2+) blocking effect. External Mn(2+) or Mg(2+) can
      compete with external Ba(2+) at the IRK1 binding site at an external Ba(2+)
      concentration of 30 mol/L and K(+) concentration of 90 mmol/L. Inactivation
      becomes slower and slower and Ba(2+) is repelled from the IRK1 binding site when
      Mg(2+) or Mn(2+) con-centration is further increased. Mg(2+), but not Mn(2+), can
      contact with deeper binding sites of IRK1 to block the channel, suggesting that
      multiple-ion blockage may exist in IRK1.

PMID- 11971172
TI  - [Expression of citrate transporter mRNA in the kidneys of rats with metabolic
      acidosis].
AB  - The purpose of the present study was to examine whether metabolic acidosis
      affects the expression of rat renal Na(+)/citrate cotransporter. Female Wistar
      rats were pair-fed with normal rat chow and drinking water (control) or water
      with 0.28 mol/L NH4Cl (metabolic acidosis). The mRNA of two renal Na(+)/citrate
      cotransporters, which were respectively expressed on apical and basolateral
      membrane, were measured by Northern blot with two probes, SDCT1 and SDCT2.
      Animals were sacrificed on day 1,3 and 7. On the 1st day, the blood plasma HCO(
      )3 of acidosis group decreased significantly (P<0.01), but the mRNA abundance did
      not change. On the 3rd day in the acidosis group, the blood plasma HCO(-)3
      increased slightly more than that on the 1st day, but was still significantly
      lower than that of the control group (P<0.01). Both the probes detected some
      increase in mRNA of brush border and basolateral Na(+)/citrate cotransporter. On
      the 7th day, the blood plasma HCO(-)3 of the acidosis group continuously
      increased and there was no significant difference between the two groups. The
      abundance of brush border and basolateral Na(+)/citrate cotransporter mRNA
      increased, but there was no difference between those of the 3rd day and the 7th
      day. It is concluded that metabolic acidosis can induce increase of Na(+)/citrate
      cotransporter mRNA, which may be responsible for hypocitraturia.

PMID- 11971173
TI  - [Protective effect of hepatocyte growth factor on hepatocyte poisoning by carbon
      tetrachloride and related gene expression in rats].
AB  - Hepatocyte growth factor (HGF), as a pleiotropic factor, plays important roles in
      organ regeneration, organogenesis and morphogenesis, but few reports on
      protective effect of HGF on injured liver are available. The aim of this work was
      to investigate protective effects of recombinant human HGF (rhHGF) on intoxicated
      hepatocytes induced by carbon tetrachloride (CCl4). The results are as follows:
      (1) rhHGF (5 ng/ml) could significantly increase the viability of hepatocytes
      intoxicated by CCl4 (15 mmol/L), decrease the leakage of intracellular alanine
      transaminase (ALT) and potassium ions into the culture medium; (2) the
      combination of rhHGF (5 ng/ml) and epidermal growth factor (EGF) (50 ng/ml) could
      increase the viability further, decrease the leakage of intracellular ALT and
      potassium ions of hepatocytes; (3) high expression of HGF and its receptor/c-met
      gene in regenerating liver after partial hepatectomy and CCl4 (50%, 2.5 ml/kg bw)
      poisoning were examined respectively by reverse transcription-polymerase chain
      reaction in rats. The results showed that rhHGF could protect hepatocytes against
      CCl4 through preventing intracellular ALT and potassium ion leakage, thus
      suggesting a synergistic effect of rhHGF and EGF on cytoprotection, and high
      expression of HGF and its receptor/c-met mRNA in the liver treated with PH and
      CCl4 poisoning. The present study suggests that the expression of HGF and its
      receptor gene plays an important role in liver regeneration and repair.

PMID- 11971174
TI  - [Role of nitric oxide in the reflex of raising biliary pressure].
AB  - Raising the biliary tract pressure from the baseline to 4 kPa significantly
      decreases arterial blood pressure and myoelectric activity of sphincter of Oddi
      (SO) (bile duct-arterial blood pressure reflex), which is sometimes associated
      with the disappearance of phasic myoelectric activity of SO (bile duct-SO
      reflex). Thirty-two rabbits were used to investigate the role of nitric oxide
      (NO) in these reflexes. On the base of increased myoelectric activity and
      arterial blood pressure by intravenous drip of 4 microgram/(kg.min)
      noradrenaline, raising the biliary tract pressure from the baseline to 4 kPa
      significantly decreased arterial blood pressure and myoelectric activity of SO.
      On the base of increased myoelectric activity and arterial blood pressure by
      intravenous injection of 10 mg/kg L-NNA, the bile duct-arterial blood pressure
      reflex disappeared in all the rabbits, but the bile duct-SO reflex disappeared
      only in a population of (3/8) and obviously decreased in the remaining ones (5/8)
      during raising biliary pressure from the baseline to 4 kPa. The bile duct-SO
      reflex after preceding local perfusion of L-NNA was similar to that after
      preceding intravenous injection of L-NNA, but bile duct-arterial blood pressure
      reflex still appeared. These findings suggest that both of these two reflexes are
      caused by the tension stimulation to the receptive area of the biliary tract, and
      may be mediated by NO.

PMID- 11971175
TI  - Effects of different kinds of stretch on voltage-dependent calcium current in
      antrial circular smooth muscle cells of the guinea-pig.
AB  - In order to elucidate the effect of membrane stretch on ionic currents, we
      employed the whole-cell patch-clamp technique to investigate the effects of
      different kinds of stretch on voltage-dependent calcium currents in antrial
      circular smooth muscle cells of the guinea-pig. The membrane stretch induced by
      superfusing the smooth muscle cells with hyposmotic bath solution enhanced
      voltage-operated calcium current and activated inward holding current. The
      increase in calcium current occurred within 1 minute of superfusion and the
      sustained inward holding current was slowly activated after prominent cell
      swelling. Voltage-dependent calcium currents (Ica) were significantly increased
      by membrane stretch which was induced by cell swelling and cell inflation, but
      was not affected by direct longitudinal stretch (110  130%) using two electrodes.
      The results suggest that the cell membrane stretch can increase voltage-dependent
      calcium channel activity and the effect of stretch on calcium channels was
      related to the membrane tension and/or the direction of membrane stretch.

PMID- 11971176
TI  - [Role of paraventricular nucleus in natriuresis and diuresis induced by volume
      expansion in rabbits].
AB  - In sham-lesioned and paraventricular nucleus (PVN) lesioned rabbits, the peak
      increases of urine volume (UV) induced by volume expansion (VE) were 0.59+/-0.09
      and 0.31+/-0.03 ml/min (P<0.01) respectively, whereas the peak increases of
      U(Na)V were respectively 66.76+/-6.74 and 36.05+/-3.44 micromol/min (P<0.01). No
      significant differences were found in the two increases induced by VE between
      rabbits with intact and those with sham-lesioned PVN. In rabbits with vagotomy
      there were no changes in the two increases after PVN lesion (P>0.05). In rabbits
      with renal denervation there was no significant change in natriuretic response
      after PVN lesion (P>0.05), but lesion of PVN significantly attenuated diuretic
      response (P<0.02). There were no significant differences in glomerular filtration
      rate (GFR) and renal plasma flow (RPF) before or after VE between the rabbits
      with intact and lesioned PVN (P>0.05). These results suggest that PVN is involved
      in the regulation of natriuresis and diuresis induced by VE, which are mediated
      by vagal afferent nerve, whereas the renal sympathetic efferent nerve may be
      involved in natriuretic response.

PMID- 11971177
TI  - High density lipoproteins enhanced antiaggregating activity of nitric oxide
      derived from bovine aortal endothelial cells.
AB  - In the present study, the effect of high density lipoproteins (HDLs) on the
      antiaggregating activity of nitric oxide (NO) derived from endothelial cells was
      investigated with the use of cultured bovine aortal endothelial cells (BAECs).
      The BAECs were placed in an aggregometer in contact with rabbit platelets after
      blocking cyclo-oxygenase with acetylsalicylic acid. Under this circumstance, the
      antiaggregating effect of endothelial cells was exclusively dependent on the
      release of NO, which was further confirmed by prevention of antiaggregating
      activity of BAECs with 1 mmol/L N(G)-Nitro-L-arginine. When this system was used,
      thrombin (0.1 U/ml) evoked 67.33+/-7.52% aggregation of rabbit platelets (2 
      10(8)/ml). This effect was inhibited by NO derived from endothelial cells (1 
      10(5)  1  10(6)/ml) in a cell number dependent manner. HDLs (1 mg/ml), added into
      the system immediately before BAECs, enhanced this antiaggregating effect of NO.
      However, incubating BAECs with HDLs for an hour and removing the HDLs by
      centrifugation did not have the same effect, unless HDLs were present during
      aggregation. No direct effect of HDLs on platelet aggregation was observed. The
      above findings suggest that HDLs can enhance the antiaggregating effects of BAECs
      mediated by direct interaction with NO.

PMID- 11971178
TI  - [Correlation between the age-related memory impairment and the level of free
      Ca(2+) in brain synaptosomes].
AB  - In this study, We investigated the changes in the ability of learning-memory of
      12-month- and 18-month-old mice, and the intrasynaptosomal Ca(2+) levels of some
      mouse brain areas (hippocampus, cerebral cortex, corpus quadrigem and cerebellum)
      on the basis of our last behavior observation and biochemistry detection.
      Meanwhile, the intrasynaptosomal Ca(2+) levels of the four brain areas were
      compared between the mice of impaired and good memory. The main results are as
      follows. With the increase of age, the ability of learning-memory of mice
      decreased significantly; and the concentration of the intrasynaptosomal free
      Ca(2+) (i) in mouse brain areas (except for cerebral cortex) increased markedly,
      especially in the memory-impaired mice. The results suggest that age-related
      memory impairment may be associated with the overloading of intrasynaptosomal
      free Ca(2+) (i).

PMID- 11971179
TI  - WRN helicase accelerates the transcription of ribosomal RNA as a component of an
      RNA polymerase I-associated complex.
AB  - Werner syndrome (WS) is a rare autosomal recessive genetic disorder causing
      premature aging. The gene (WRN) responsible for WS encodes a protein homologous
      to the RecQ-type helicase. WRN has a nucleolar localization signal and shows
      intranuclear trafficking between the nucleolus and the nucleoplasm. WRN is
      recruited into the nucleolus when rRNA transcription is reactivated in quiescent
      cells. Inhibition of mRNA transcription with alpha-amanitin has no effect on
      nucleolar localization of WRN whereas inhibition of rRNA transcription with
      actinomycin D releases WRN from nucleoli, suggesting that nucleolar WRN is
      closely related to rRNA transcription by RNA polymerase I (RPI). A possible
      function of WRN on rRNA transcription through interaction with RPI is supported
      by the results described here showing that WRN is co-immunoprecipitated with an
      RPI subunit, RPA40. Here we show that WS fibroblasts are characterized by a
      decreased level of rRNA transcription compared with wild-type cells, and that the
      decreased level of rRNA transcription in WS fibroblasts recovers when wild-type
      WRN is exogenously expressed. By contrast, exogenously expressed mutant-type WRN
      lacking an ability to migrate into the nucleolus fails to stimulate rRNA
      transcription. These results suggest that WRN promotes rRNA transcription as a
      component of an RPI-associated complex in the nucleolus.

PMID- 11971180
TI  - TAp63gamma (p51A) and dNp63alpha (p73L), two major isoforms of the p63 gene,
      exert opposite effects on the vascular endothelial growth factor (VEGF) gene
      expression.
AB  - Tumor suppressor p53 has been shown to repress expression of vascular endothelial
      growth factor (VEGF), an endothelial cell-specific mitogen and a key mediator of
      tumor angiogenesis. The p63 gene, recently identified as a p53-relative, encodes
      multiple isoforms with structural and functional similarities and differences
      from p53. In this study, we show the evidence that the two major isoforms of the
      p63 gene, TAp63gamma (p51A) and dNp63alpha (p73L), represses and upregulates VEGF
      expression, respectively, on transcription and protein levels. Transient
      transfection assays show that a hypoxia-inducible factor (HIF) 1 binding site
      within the VEGF promoter region is responsible for both upregulation and
      repression by dNp63alpha and by TAp63gamma, respectively, of the VEGF promoter
      activity. We also show that TAp63gamma targets HIF1alpha for promoting
      proteasomal degradation but that dNp63alpha targets HIF1alpha for stabilization.
      Mammalian two-hybrid assays show that HIF1alpha-dependent transcription is
      repressed by TAp63gamma as well as by p53, whereas it is upregulated by
      dNp63alpha in collaboration with a transcription coactivator p300. Our data also
      show that dNp63alpha acts as a dominant-negative reagent toward both p53- and
      TAp63gamma-mediated degradation of HIF1alpha and repression of HIF1alpha
      dependent transcription. These results suggest that p63 is involved in the
      regulation of the VEGF gene expression and that modulation of VEGF expression by
      TAp63gamma and dNp63alpha is closely correlated with their distinct roles on the
      regulation of HIF1alpha stability.

PMID- 11971181
TI  - Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal
      expansion of CD4(+)25(+) HTLV-1-infected T-cells in human carriers of both HTLV-1
      and S. stercoralis.
AB  - The intermediate state of HTLV-1 infection, often found in individuals dually
      infected with Strongyloides stercoralis (S. stercoralis) and HTLV-1, is assumed
      to be a preleukemic state of adult T-cell leukemia (ATL). To investigate the
      effects of S. stercoralis superinfection on the natural history of HTLV-1
      infection, we characterized peripheral blood samples of these individuals in
      Okinawa, Japan, an endemic area for both HTLV-1 and S. stercoralis and we studied
      effects of the parasite antigen on T-cells. The dually infected individuals
      showed a significantly higher provirus load and an increase in CD4(+)25(+) T cell
      population, with a significant, positive correlation. This increase was
      attributable to polyclonal expansion of HTLV-1-infected cells, as demonstrated by
      inverse-long PCR analysis of the integration sites. S. stercoralis antigen
      activated the IL-2 promoter in reporter gene assays, induced production of IL-2
      by PBMC in vitro, and supported growth of IL-2 dependent cell lines immortalized
      by HTLV-1 infection or the transduction of Tax. Taken collectively, these results
      indicate that S. stercoralis infection induces polyclonal expansion of HTLV-1
      infected cells by activating the IL-2/IL-2R system in dually infected carriers,
      an event which may be a precipitating factor for ATL and inflammatory diseases.

PMID- 11971182
TI  - Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary bladder
      cancer.
AB  - The chromosomal region 12q13-q15 is recurrently amplified in bladder cancer.
      Putative target genes located in this region include MDM2, CDK4, and GLI. To
      evaluate the involvement of these genes in bladder cancer, we screened a tissue
      microarray (TMA) containing 2317 samples by fluorescence in situ hybridization
      (FISH). Amplification was found for MDM2 in 5.1%, for CDK4 in 1.1%, and for GLI
      in 0.4% of interpretable tumors. Among tumors having amplification of at least
      one of these 12q13-q15 genes, 76.6% had amplification of MDM2 alone and 6.4% had
      amplification of CDK4 alone. Coamplifications were seen of MDM2 and CDK4 in
      10.6%, and of CDK4 and GLI in 6.4%. Neither coamplifications of all three genes
      nor isolated GLI amplifications were found. These data suggest a prominent role
      of MDM2 as a 12q13-q15 amplification target in bladder cancer. However,
      independent CDK4 amplifications do also occur suggesting either two non
      overlapping amplification sites or else a minimal overlapping region between MDM2
      and CDK4 perhaps containing another yet unknown oncogene. The frequency of
      amplification increased significantly from stage pTa to pT1-4 (P<0.04) and from
      low to high grade (P<0.005). These data are consistent with a high level of
      genetic instability in invasively growing and high-grade bladder tumors.

PMID- 11971183
TI  - Immortalized embryonic mouse fibroblasts lacking the RelA subunit of
      transcription factor NF-kappaB have a malignantly transformed phenotype.
AB  - The RelA transcription factor is part of dimeric complexes, most commonly either
      p50-RelA (NF-kappaB) heterodimers or RelA homodimers, that control a variety of
      cellular processes. Immortalized embryonic fibroblasts established from rela
      knockout mice have previously been shown to be more sensitive to apoptosis
      induced by tumor necrosis factor (TNF) than are control fibroblasts. In this
      report, we show that one line of rela-/- fibroblasts has additional phenotypes
      that distinguish them from control mouse fibroblasts. As compared to normal 3T3
      cells, RelA-deficient fibroblasts have a spindled morphology, are less adherent
      to culture dishes, grow to a higher saturation density, and can form colonies in
      soft agar. These properties are consistent with a weakly transformed phenotype
      for rela-/- cells. Furthermore, RelA-deficient fibroblasts can form tumors in
      immunodeficient mice, but these tumors regress, probably because of the
      sensitivity of these cells to TNF. The ability of rela-/- fibroblasts to form
      colonies in soft agar can be reverted by re-expression of wild-type mouse RelA,
      but not by expression of RelA mutants that cannot form homodimers. There is no
      clear correlation between the absence of RelA and the levels of expression of
      other Rel/NF-kappaB family members or adhesion proteins (ICAM-1 and VCAM-1) whose
      genes have upstream kappaB sites. Taken together, these results suggest that RelA
      has tumor suppressing activity under some circumstances and that RelA complexes
      are involved in the control of a variety of cellular properties associated with
      oncogenesis.

PMID- 11971184
TI  - Ligand-independent signaling by overexpressed CD30 drives NF-kappaB activation in
      Hodgkin-Reed-Sternberg cells.
AB  - Overexpression of CD30 and constitutive NF-kappaB activation characterizes tumor
      cells of Hodgkin's disease (HD), Hodgkin and Reed-Sternberg (H-RS) cells. We
      report that in H-RS cells overexpression of CD30 leads to self-aggregation,
      recruitment of TRAF2 and TRAF5, and NF-kappaB activation, independent of CD30
      ligand. CD30 and TRAF proteins co-localized in H-RS cell lines and in lymph nodes
      of HD. An adenovirus-vector carrying a decoy CD30 lacking the cytoplasmic region
      or a dominant negative IkappaBalpha mutant blocks NF-kappaB activation, down
      regulates IL-13 expression and induces apoptosis. Thus, in H-RS cells, ligand
      independent activation of CD30 signaling drives NF-kappaB activation and this
      leads to constitutive cytokine expression, which provides a molecular basis for
      HD. Inhibition of NF-kappaB activation by adenovirus vector-mediated gene
      transfer may provide a novel strategy of cell- and target molecule-specific
      therapy for patients with HD.

PMID- 11971185
TI  - Stat1 negatively regulates angiogenesis, tumorigenicity and metastasis of tumor
      cells.
AB  - Stat1 is deficient or inactive in many types of human tumors whereas some tumors
      have activated Stat1. Whether Stat1 affects tumor growth and metastasis is
      unclear. In the present study, we used Stat1 knockout tumor cells to determine
      (1) whether Stat1 can regulate angiogenesis, growth, and metastasis of tumor
      cells; and (2) whether Stat1 is required for the inhibitory effect of IFN-beta on
      the expression of angiogenic factor bFGF. Highly tumorigenic and metastatic RAD
      105 tumor cells derived from a fibrosarcoma of a Stat1 knockout mouse were
      reconstituted with a Stat1 expression vector. The reconstitution of Stat1
      suppressed the tumorigenicity and metastasis of RAD-105 cells in nude mice which
      correlated with a decreased microvessel density and decreased expression of
      proangiogenic molecules bFGF, MMP-2, and MMP-9 in vivo. Moreover, noncytotoxic
      concentrations of IFN-beta significantly inhibited the in vitro expression of
      bFGF in the Stat1-reconstituted cells but not in the Stat1-deficient cells, which
      was consistent with decreased bFGF expression of Stat1-reconstituted tumors in
      vivo. Therefore, Stat1 is essential for IFN-mediated inhibition of bFGF
      production, suggesting that tumor-intrinsic Stat1 is an important mediator for
      antiangiogenic signals, such as IFN. Collectively, these data demonstrate that
      Stat1 expressed by tumor cells is a negative regulator of tumor angiogenesis and,
      hence, tumor growth and metastasis.

PMID- 11971186
TI  - Inhibition of FAK signaling activated by urokinase receptor induces dormancy in
      human carcinoma cells in vivo.
AB  - Activation of focal adhesion kinase (FAK), overexpressed in several human
      cancers, induces survival, proliferation and motility of cells in culture, but
      its functional importance in human tumor growth in vivo has not been elucidated.
      I explored the role of FAK in regulating tumorigenicity of human carcinoma cells,
      HEp3. These cells overexpress urokinase receptor (uPAR) which, by activating
      alpha5beta1 integrin, initiates an intracellular signal through FAK and Src
      leading to ERK activation and tumorigenicity in vivo. Down regulation of uPAR in
      these cells led to an approximately 3-5-fold reduction in FAK phosphorylation and
      association with Src and dormancy in vivo. Both FAK phosphorylation and ability
      to grow in vivo were restored by re-expression of uPAR. The FAK signaling pathway
      in T-HEp3 cells, measured by FAK phosphorylation, GTP-loaded Ras and ERK
      activation, was inhibited by transient or stable transfection of FAK related non
      kinase (FRNK), known to have a dominant negative function, but not by a FRNK
      mutant version (S1034-FRNK). Most importantly, while vector- and mutant-S1034
      FRNK transfected cells inoculated onto chicken embryo CAMs formed progressively
      growing tumors, the HA-FRNK-expressing T-HEp3 cells did not proliferate in vivo
      and remained dormant for at least 6 weeks. Both cell types had similar rate of
      apoptosis in vivo and the p38(SAPK) or PI3K-Akt signaling pathways were
      unaffected by FRNK. FRNK induced dormancy could be reverted by expression of an
      active-R4F-Mek1 mutant. These results show that active FAK is an important
      mediator of uPAR-regulated tumorigenicity of HEp3 cells and that interruption of
      FAK mitogenic signaling either through down-regulation of uPAR or by expression
      of FRNK can force human carcinoma cells into dormancy.

PMID- 11971187
TI  - Increased error-prone non homologous DNA end-joining--a proposed mechanism of
      chromosomal instability in Bloom's syndrome.
AB  - BS is an inherited cancer predisposition disorder caused by inactivation of the
      RecQ family helicase, BLM. One of the defining features of cells from BS
      individuals is chromosomal instability, characterized by elevated sister
      chromatid exchanges (SCEs), as well as chromosomal breaks, deletions, and
      rearrangements. Although the basis for chromosomal instability is poorly
      understood, there is evidence that chromosomal abnormalities can arise through an
      alteration in the efficiency or fidelity of DNA double strand break (DSB) repair.
      Here, we show that BS cells demonstrate aberrant DSB repair mediated by the non
      homologous end-joining (NHEJ) pathway for DNA repair, one of the two main
      pathways for the repair of DSBs in mammalian cells. Through a comparison of BS
      cell lines, and a derivative in which the BS phenotype has been reverted by
      expression of the BLM cDNA, we show that BS cells display aberrant end-joining of
      DSBs. Importantly, DNA end-joining in BS cells is highly error-prone and
      frequently results in DNA ligation at distant sites of microhomology, creating
      large DNA deletions. This aberrant repair is dependent upon the presence of the
      Ku70/86 heterodimer, a key component in the NHEJ pathway. We propose that
      aberrant NHEJ is a candidate mechanism for the generation of chromosomal
      instability in BS.

PMID- 11971188
TI  - Induction and endoplasmic reticulum location of BIK/NBK in response to apoptotic
      signaling by E1A and p53.
AB  - A DNA microarray analysis identified the BH3-only BCL-2 family member, BIK/NBK,
      as a transcript that is upregulated during induction of apoptosis by oncogenic
      E1A. E1A depended on wild-type p53 to induce BIK and activate the death program.
      Further, p53 independently induced BIK RNA and protein, and BIK alone stimulated
      cell death in p53-null cells, dependent on the activation of caspases. BIK
      function, however, was abrogated by a disabling point mutation within the BH3
      domain. Collectively, these results argue that BIK is a downstream apoptotic
      effector of p53 in response to a physiological p53-mediated death stimulus
      provided by E1A. Elevated BCL-2 functioned downstream of p53 and BIK induction to
      inhibit the E1A death pathway, with the ratio of anti-apoptotic BCL-2 and pro
      apoptotic BIK determining cell death or survival in E1A-expressing cells. Cells
      expressing BCL-2 or treated with the pan caspase inhibitor, zVAD-fmk, allowed
      accumulation of high levels of cytotoxic BIK compared to control cells. Of note,
      a significant fraction of either ectopic or endogenous BIK was found associated
      with the endoplasmic reticulum, suggesting that this organelle, in addition to
      mitochondria, may be a target of BIK function.

PMID- 11971189
TI  - Localization of mLin-7 at nectin-based cell-cell junctions.
AB  - In C. elegans, lin-7 as well as lin-2/lin-10 is involved in the proper
      localization of the LET-23 receptor tyrosine kinase that regulates vulval
      induction. The mammalian homologue, mLin-7, forms a ternary complex with the
      mammalian homologues of LIN-2 and LIN-10 and localizes at cell-cell junctions in
      epithelial cells, but the mechanism of this localization of mLin-7 is unknown.
      Nectin is an immunoglobulin-like cell-cell adhesion molecule that is involved in
      organization of adherens and tight junctions in epithelial cells. Nectin is
      indirectly associated with the cadherin-catenin system and the actin cytoskeleton
      through afadin, an actin filament-binding protein. We showed here that mLin-7
      localized at the nectin-based cell-cell junctions. This localization of mLin-7
      required the interaction of nectin with afadin, but not the cadherin-catenin
      system or the actin cytoskeleton. mLin-7 did not directly interact with nectin or
      afadin. The results indicate that mLin-7 localizes at cell-cell junctions through
      the nectin-afadin system.

PMID- 11971190
TI  - Mechanism of constitutive activation of FLT3 with internal tandem duplication in
      the juxtamembrane domain.
AB  - Internal tandem duplication (ITD) of the juxtamembrane (JM) domain of FLT3 is the
      most frequent mutation in human acute myeloid leukemia, and is significantly
      associated with leukocytosis and a poor prognosis. Previously we reported that
      FLT3 with ITD (FLT3/ITD) formed a homodimer and was autophosphorylated on
      tyrosine residues, while the mechanism remains unclear. In this study, we
      elucidated the role of the JM domain in FLT3 activation. Mutant FLT3 with not
      only ITD but also an elongating or shortening JM domain transformed murine IL3
      dependent myeloid progenitor cell line 32D regardless of the tyrosine residues in
      the JM domain. These mutant FLT3s were constitutively tyrosine phosphorylated and
      activated signal-transduction molecules such as SHC, MAP kinase and STAT5a.
      Notably, co-transfection of the truncated FLT3/ITD lacking kinase and C-terminal
      domains with the wild type (Wt)-FLT3 into 32D cells resulted in the autonomous
      proliferation. In these cells, truncated FLT3/ITD generated a hetero-complex with
      Wt-FLT3 and Wt-FLT3 was constitutively tyrosine phosphorylated. These findings
      indicate that the FLT3 JM domain plays an important role in receptor activation,
      and that the length-mutated JM domain induces ligand-independent receptor
      activation but also activates Wt-FLT3 in a trans-manner.

PMID- 11971191
TI  - Loss of methylation at chromosome 11p15.5 is common in human adult tumors.
AB  - Chromosome 11p15 deletion is frequent in human tumors, suggesting the presence of
      at least one tumor suppressor gene within this region. While mutation analyses of
      local genes revealed only rare mutations, we have previously described a
      mechanism, gain of imprinting, that leads to loss of expression of genes located
      on the maternal 11p15 chromosome in human hepatocarcinomas. Loss of expression
      was often associated with loss of maternal-specific methylation at the KvDMR1
      locus. Here, we show that loss of the maternal KvDMR1 methylation is common,
      ranging from 30 to 50%, to a variety of adult neoplasms, including liver, breast,
      cervical and gastric carcinomas. We found that other 11p15.5 loci were
      concomitantly hypomethylated, indicating that loss of KvDMR1 methylation occurred
      in the context of a common mechanism affecting the methylation of a large 11p15
      subchromosomal domain. These epigenetic abnormalities were not detected in any
      normal somatic tissue. Therefore, it seems possible that, contrary to the
      repression of promoter activity caused by hypermethylation, loss of gene
      expression at 11p15.5 may result from the activation, by hypomethylation, of one
      or more negative regulatory elements.

PMID- 11971192
TI  - Dual-specificity protein tyrosine phosphatase VHR down-regulates c-Jun N-terminal
      kinase (JNK).
AB  - The JNK group (for c-Jun N-terminal kinase) of mitogen-activated protein kinases
      (MAP kinases) is activated in cells in response to environmental stress and
      cytokines. Activation of JNK is the result of dual phosphorylation by specific
      upstream kinases which phosphorylate the TxY motif. Much less is known concerning
      the down-regulation by protein phosphatases. Here, we demonstrate that the
      tyrosine-specific and constitutively-expressed phosphatase VHR (for VH1-Related)
      down-regulates the JNK signaling pathway at the level of JNK dephosphorylation.
      VHR was shown to efficiently dephosphorylate JNK and to form a tight complex with
      activated JNK when the catalytically-inactive C124S VHR mutant was employed as an
      in vivo substrate trap. Utilizing an in vitro assay, the transcription factor c
      Jun specifically inhibited the ability of VHR to dephosphorylate JNK, likely by
      sterically blocking access to the phosphorylation sites when JNK and c-Jun form a
      complex. c-Jun has no effect on the ability of VHR to inactivate the ERK MAP
      kinases or to hydrolyze artificial substrates. The c-Jun inhibition results are
      discussed in terms of the resistant-nature of JNK dephosphorylation in cellular
      extracts and in terms of a general model in which VHR may be a general MAP kinase
      phosphatase whose specificity and activity are dictated by the presence of MAP
      kinase-associated proteins that inhibit dephosphorylation.

PMID- 11971193
TI  - Cooperation between heparin-binding EGF-like growth factor and interleukin-6 in
      promoting the growth of human myeloma cells.
AB  - Interleukin-6 (IL-6) is a major survival and proliferation factor of human
      malignant plasma cells and IL-6 dependent myeloma cell lines can be obtained from
      patients with terminal disease. We show here that mutated diphtheria toxin, a
      specific inhibitor of heparin-binding epidermal growth factor-like growth factor
      (HB-EGF), blocked the IL-6-induced growth of two myeloma cell lines (XG-1 and XG
      14) and did not significantly affect that of two other cell lines (XG-6 and XG
      13). The IL-6 mediated growth of myeloma cells was also inhibited by antibodies
      to ErbB1, a receptor for HB-EGF. The XG-1 and XG-14 cell lines that are sensitive
      to HB-EGF inhibitors overexpressed HB-EGF and EGF receptor (ErbB1) genes. They
      also overexpressed CD9, a tetraspanin that binds to the heparin-binding domain of
      HB-EGF and is critical for promoting ErbB1 activation by HB-EGF. The XG-6 and XG
      13 myeloma cells that were not significantly sensitive to HB-EGF antagonists,
      poorly expressed HB-EGF, ErbB1 and CD9 genes or proteins. We demonstrated that
      recombinant HB-EGF supported the long-term growth of myeloma cells, as did IL-6.
      The myeloma cell growth factor activity of HB-EGF was completely inhited by
      antibodies to ErbB1, but also by antibodies to gp130 IL-6 transducer or to IL-6.
      These data indicate that in the XG-1 and XG-14 IL-6-dependent myeloma cell lines,
      the CD9/HB-EGF/erbB1 and the IL-6/IL-6R/gp130 pathways cooperate synergistically
      to trigger myeloma cell growth. They suggest that inhibitors of the EGF receptor
      or HB-EGF may be useful for inducing myeloma cell apoptosis in patients with
      multiple myeloma.

PMID- 11971194
TI  - Genetic mechanisms of hepatocarcinogenesis.
AB  - The development of hepatocellular carcinoma (HCC) is a multistep process
      associated with changes in host gene expression, some of which correlate with the
      appearance and progression of tumor. Preneoplastic changes in gene expression
      result from altered DNA methylation, the actions of hepatitis B and C viruses,
      and point mutations or loss of heterozygosity (LOH) in selected cellular genes.
      Tumor progression is characterized by LOH involving tumor suppressor genes on
      many chromosomes and by gene amplification of selected oncogenes. The changes
      observed in different HCC nodules are often distinct, suggesting heterogeneity on
      the molecular level. These observations suggest that there are multiple, perhaps
      redundant negative growth regulatory pathways that protect cells against
      transformation. An understanding of the molecular pathogenesis of HCC may provide
      new markers for tumor staging, for assessment of the relative risk of tumor
      formation, and open new opportunities for therapeutic intervention.

PMID- 11971195
TI  - Multiple lysine mutations in the C-terminus of p53 make it resistant to
      degradation mediated by MDM2 but not by human papillomavirus E6 and induce growth
      inhibition in MDM2-overexpressing cells.
AB  - We have recently shown that lysine mutations in p53's putative C-terminal
      acetylation sites result in increased stability and cytoplasmic distribution of
      the p53 protein in a human lung cancer cell line. In the present study, we showed
      that when lysine residues 372, 373, 381, and 382 of p53 were substituted with
      alanine, the resulting A4 protein was resistant to MDM2-mediated proteosomal
      degradation but was highly sensitive to human papillomavirus E6-mediated
      proteolysis. When A4 and wild-type p53 were transfected into MDM2-overexpressing
      MCF-7 cells, A4 significantly reduced colony formation in vitro, when compared
      with wild-type p53. Our results suggest that A4 exerts a growth-inhibitory effect
      more efficiently than wild-type p53 does in cell lines that overexpress MDM2 and
      may therefore be a better therapeutic tool than wild-type p53 for certain cancers
      in which MDM2 is amplified or overexpressed.

PMID- 11971197
TI  - Treatment of late stage sleeping sickness caused by T.b. gambiense: a new
      approach to the use of an old drug.
AB  - Melarsoprol is the standard treatment of late stage trypanosomiasis. The
      development of treatment schedules was previously purely empirical. Generally
      melarsoprol is given in 3 series of three to four consecutive injections, given
      every 24 hours, with an interval of about one week between the series. Based on
      pharmacokinetic analysis, computer simulations and extensive literature research
      covering all schedules previously used and tested, a new schedule, consisting of
      ten daily consecutive doses of 2.16 mg/kg of the drug was suggested. The
      pharmacokinetic model was validated in uninfected vervet monkeys. No unexpected
      drug accumulation and no systemic toxic effects were observed. In a pilot
      clinical trial in Congo RDC a small group of T. b. gambiense patients (n = 11)
      was treated successfully with the new schedule. In an open randomised clinical
      trial conducted in 500 patients in Angola the clinical efficacy and safety of
      this new concise treatment were compared to those of standard protocol treatment.
      Parasitological cure 24 hours after treatment was 100% in both groups.
      Statistical analysis yielded no significant differences for adverse events
      between the two treatment protocols. The new schedule reduces the amount and cost
      for the drug by about one third, and those for hospitalisation by about half.

PMID- 11971198
TI  - Expression of the hMSH6 mismatch-repair protein in colon cancer and HeLa cells.
AB  - PRINCIPLES: 10 to 15% of human colon cancers are associated with an inherited or
      somatic defect of the DNA Mismatch Repair (MMR) system, which has evolved to
      correct biosynthetic errors such as nucleotide mis-incorporations or
      misalignments arising during DNA replication in the S phase of the cell-cycle.
      Although expression of the MMR genes was expected to be cell-cycle dependent, we
      and others observed that the MMR proteins hMSH2 and hMLH1 are expressed
      constitutively in proliferating cells. METHODS: In this study we extend our
      observations to another essential MMR protein, hMSH6. We used
      immunohistochemistry to evaluate the expression pattern of this protein in human
      colorectal mucosa and tumours, as well as in synchronised HeLa-S3 cells, in which
      we analysed its steady-state levels during the cell-cycle. RESULTS: We show that
      the immunohistochemical pattern of expression of hMSH6 in normal colorectal
      crypts and in colon cancers differs significantly from that of the other MMR
      proteins, with a much lower percentage of replicating cells being hMSH6-positive.
      This implies that hMSH6 could be cell-cycle regulated. In order to test this
      hypothesis in a model system, we synchronised HeLa-S3 cells with mitotic shake
      off and found that the hMSH6 protein was detectable throughout the cell-cycle,
      but that its steady-state level increased when cells progressed from G1 to S
      phase. DISCUSSION: The increase of hMSH6 steadystate level when cells enter S
      phase was expected, since MMR acts during DNA replication. However, the overall
      low level of oscillations of hMSH6 during the cell-cycle in this cellular model
      apparently does not fit the immunohistochemical phenotype. We believe that this
      discrepancy is due to the fact that human cell lines proliferate at a much higher
      rate than normal and neoplastic colorectal cells in vivo.

PMID- 11971199
TI  - Abortion in woman caused by caprine Chlamydophila abortus (Chlamydia psittaci
      serovar 1).
AB  - On a farm housing cattle and goats an abortion storm occurred affecting 50% of
      the goats during the lambing season 2000/2001. In one of three investigated
      caprine abortions Chlamydophila abortus could be identified as aetiology. During
      this time a pregnant woman (pregnancy week 19/20) had contact with aborting
      goats. She developed a severe generalized infection and aborted. The placenta
      contained Chlamydophila abortus shown by immunohistochemistry and PCR. The aim of
      the present case report is to alert medical doctors about the potential zoonotic
      risk of ovine/caprine abortions.

PMID- 11971200
TI  - Management of chronic obstructive pulmonary disease: the Swiss guidelines.
      Official Guidelines of the Swiss Respiratory Society.

PMID- 11971201
TI  - Otto Naegeli Award 2002 honors the work of Prof. Walter Wahli.

PMID- 11971202
TI  - Peroxisome proliferator-activated receptors (PPARs): from metabolic control to
      epidermal wound healing.
AB  - Peroxisome proliferator-activated receptors control many cellular and metabolic
      processes. They are transcription factors belonging to the family of ligand
      inducible nuclear receptors. Three isotypes called PPARalpha, PPARbeta/delta and
      PPARgamma have been identified in lower vertebrates and mammals. They display
      differential tissue distribution and each of the three isotypes fulfills specific
      functions. PPARalpha and PPARgamma control energy homoeostasis and inflammatory
      responses. Their activity can be modulated by drugs such as the hypolipidaemic
      fibrates and the insulin sensitising thiazolidinediones (pioglitazone and
      rosiglitazone). Thus, these receptors are involved in the control of chronic
      diseases such as diabetes, obesity, and atherosclerosis. Little is known about
      the main function of PPARbeta, but it has been implicated in embryo implantation,
      tumorigenesis in the colon, reverse cholesterol transport, and recently in skin
      wound healing. Here, we present recent developments in the PPAR field with
      particular emphasis on both the function of PPARs in lipid metabolism and energy
      homoeostasis (PPARalpha and PPARgamma), and their role in epidermal maturation
      and skin wound repair (PPARalpha and PPARbeta).

PMID- 11971203
TI  - Bronchial asthma and self-management education: implementation of Guidelines by
      an interdisciplinary programme in health network.
AB  - Asthma is a chronic disease generating very high costs even for Switzerland. Self
      management education (SME) is effective and recommended as an integral part of
      management in the most recent guidelines on asthma treatment. Its aim is to
      reduce morbidity [hospitalisations (H), lost workdays (LW), emergency
      consultations (EC)] and improve quality of life (QOL) in these patients. METHOD:
      Integrated programme with educational platforms (two-language booklet), SME in 66
      patients (30 m, 36 f) with interdisciplinary quality team (pneumologists, primary
      care physicians, pharmacists, specialised nursing staff), QOL questionnaire.
      Measurement of morbidity parameters 12 months before and after SME. Measurement
      of QOL before and 12 months after SME. RESULTS: Hospitalisations fell from 35 to
      8%*, EC from 88 to 53%*. and LW from 39 to 14%* (*p <0.001). Overall, SME
      resulted in a health cost saving of CHF 202,510 in terms of LW and CHF 131,200 in
      terms of days in hospital, i.e. a total of CHF 333,710. Costs saved per patient
      were CHF 5,056 per year. QOL improved with the following scores: overall QOL 4.5
      +/- 0.9 to 5.2 +/- 0.9*; activities 4.5 +/- 0.9 to 5.2 +/- 0.9*; symptoms 4.2 +/-
      1.1 to 5.2 +/- 1.1*; emotions 4.9 +/- 1.1 to 5.6 +/- 1*; environment 4.5 +/- 1.4
      to 4.9 +/- 1.3* (*p <0.001). CONCLUSION: SME by interdisciplinary health network
      is effective. It brings a steep fall in costs for asthma treatment by cutting
      back hospitalisations and lost workdays and by improving the asthmatics' quality
      of life. It should be recognised and better supported by the health system.

PMID- 11971205
TI  - Papaverine, a vasodilator with antiviral activity.

PMID- 11971204
TI  - Musculoskeletal involvement of brucellosis in different age groups: a study of
      195 cases.
AB  - OBJECTIVE: The aim of the present study was to determine the distribution and
      characteristics of arthritis in 195 patients with musculoskeletal involvement due
      to brucellosis in different age groups in the southeastern region of Turkey.
      PATIENTS AND METHODS: We carried out a retrospective analysis of 283 patients
      with brucellosis records and identified 195 with musculoskeletal involvement.
      Patients were classified into acutesubacute (<12 months) and chronic (>12 months)
      brucellosis. Patients were also classified into three age groups: <15 years old
      (group A), 15-45 years (group B), and over 45 years (group C). In addition,
      patients were classified into five subgroups according to type of arthritis:
      peripheral arthritis, polyarthritis, spondylitis, sacroiliitis, and
      spondylitis/sacroiliitis. RESULTS: 195 (69%) of the 283 patients [138 female
      (49%), 145 male (51%)] had musculoskeletal involvement. Of the patients with
      musculoskeletal involvement 113 (58%) were female and 82 (42%) were male, ranging
      in age from 3 to 71 years (mean age 33.14 +/- 15.03). Of 195 patients studied, 39
      (14%) were <15 years old (group A), 122 (43%) were aged 15-45 (group B), and 34
      (12%) were over 45 (group C). The most commonly affected joints were the
      sacroiliac joint in 108 patients (55%), peripheral joints in 106 (54%), and
      spondylitis in 60 (31%). Of 108 patients with sacroiliitis, 19 were in group A,
      76 in group B, and 13 in group C. Bilateral sacroiliitis was less common in group
      B (23 patients) than in groups A (3) and C (3) (p <0.05). Spondylitis was more
      common in group B (18%). Sacroiliitis and polyarthritis were more common than
      other types of musculoskeletal involvement in females, whereas in males the
      distribution of all types was similar. In patients aged under 15 and 15-45,
      sacroiliitis and polyarthritis were common compared with other types of
      arthritis, but the distribution was similar in patients over 45. CONCLUSION: In
      southeastern Anatolia musculoskeletal involvement in brucellosis is frequent. The
      series presented suggests that musculoskeletal involvement in group A is higher
      than groups A and C. The prevalence of musculoskeletal involvement appears to
      differ according to age, sex and clinical type.

PMID- 11971206
TI  - Curriculum design for problem-based learning on a volunteer basis: a Yonsei
      approach.
AB  - Innovative new medical programs such as Problem Based Learning (PBL) are being
      developed worldwide. An increasing number of medical schools are starting to
      introduce these programs into or even to replace the existing curriculum. At
      Yonsei University College of Medicine (YUCM), we developed our own PBL curriculum
      and evaluation method. In order to develop a program suitable for our school, we
      suggest that for trial purposes, a small number of student and teacher volunteers
      should be selected and that the tutors involved in the program be given adequate
      training.

PMID- 11971207
TI  - Identification of tumor suppressor loci on the long arm of chromosome 4 in
      primary small cell lung cancers.
AB  - Recent cytogenetic studies have indicated that loss of the long arm of chromosome
      4 is a frequent event in small cell lung cancer (SCLC), which suggests the
      presence of tumor suppressor genes there. To precisely map tumor-suppressor loci
      on chromosome 4q for further positional cloning efforts, we tested 15 primary
      SCLCs. Forty two polymorphic microsatellite markers located on chromosome 4q were
      used in the microsatellite analysis. We found that 12 (80%) of the 15 tumors
      exhibited loss of heterozygosity (LOH) in at least one of the tested
      microsatellite markers, and that 3 (25%) of these 12 tumors exhibited a larger
      area of deletion on chromosome 4q. Frequent LOH, defined as occurring in more
      than 50% of the tumors, was observed in five commonly deleted regions on 4q,
      namely 4q24, 4q27-28.3, 4q33, 4q34.1, and 4q34.3-35.2. Of these 5, LOH at 4q33
      was the most frequent (61.5%). Six (40%) of the 15 tumors exhibited shifted bands
      in at least one of the tested microsatellite markers. Shifted bands occurred in
      3.7% (23 of 630) of the loci tested. Our data demonstrated that at least five
      tumor-suppressor loci exist on the long arm of chromosome 4 and that they may
      play an important role in the development and progression of primary small cell
      lung cancer tumorigenesis.

PMID- 11971208
TI  - Clinicopathologic review of pulmonary silicone embolism with special emphasis on
      the resultant histologic diversity in the lung--a review of five cases.
AB  - It is known that the subcutaneous injection of silicone can lead to severe
      pulmonary complications, followed in some patients by respiratory failure.
      Currently, silicone is being increasingly applied in the field of plastic surgery
      and, unfortunately, the illicit injection of silicone fluid by uncertified
      practitioners is not uncommon in Korea. We offer a critical pathologic review of
      5 cases of pulmonary silicone embolism following illegal injection to the vaginal
      wall, four of which were fatal and came to legal autopsy. Our findings again
      confirm that subcutaneously injected silicone can gain access to the pulmonary
      vascular tree and cause pulmonary embolism. The histologic changes observed in
      the lung are variable and include four patterns i.e., the mere presence of
      silicone emboli, congestion and hemorrhage, acute pneumonitis, and diffuse
      alveolar damage despite the severe critical course in all cases. We were unable
      to find any histologic pattern that correlates well with the clinical course.
      Apart from producing emboli in the pulmonary vessels, subcutaneous injection of
      silicone can obviously cause serious pulmonary disease due to its ability to
      induce acute to induce acute pneumonitis and even possibly acute respiratory
      distress syndrome.

PMID- 11971209
TI  - Familial correlation and heritability for cardiovascular risk factors.
AB  - The goal of this study was to describe the overall genetic contribution of
      phenotypic variation to cardiovascular disease. The study population included
      7,589 family members of 1,891 families, derived from Korean Medical Insurance
      Corporation. The risk factors considered were systolic blood pressure (SBP),
      diastolic blood pressure (DBP), body mass index (BMI), and high serum
      cholesterol. The levels of cardiovascular disease risk factors were adjusted for
      age, gender, smoking and alcohol drinking. Heritability was estimated from the
      slope of the line linear regression of offspring on mid-parent. All risk factors
      showed positive familial correlations, and correlations were generally lower for
      spouses than for parent- offspring pairs. Spouse correlations showed increasing
      patterns with age. Parents-offspring correlations showed little variation with
      age, suggesting that the observed correlations with CVD risk factors were
      primarily due to genetic influences rather than environmental effects. Estimated
      heritabilities were 26% for BMI, 26% for high serum cholesterol, 19% for SBP, and
      9% for DBP. These results highlight the importance of considering genetic factors
      in studies of cardiovascular risk factors.

PMID- 11971210
TI  - Effect of ultraviolet light on the expression of adhesion molecules and T
      lymphocyte adhesion to human dermal microvascular endothelial cells.
AB  - In order to determine the effect of ultraviolet radiation (UVR) on the cell
      adhesion molecules expressed in human dermal microvascular endothelial cells
      (HDMEC), the cells were exposed to varying UVR doses and the cell surface was
      examined for expression of intercellular cell adhesion molecule-1 (ICAM-1),
      vascular cell adhesion molecule-1 (VCAM- 1), and E-selectin. The effect of UVB
      irradiation on the binding of T lymphocytes to HDMEC was also examined. UVA
      irradiation did not affect the surface expression of ICAM-1, VCAM-1, or E
      selectin on the HDMEC. However, following UVB exposure, ELISA demonstrated a
      significant increase in the baseline ICAM-1 cell surface expression on the HDMEC.
      However, no induction of either E-selectin or VCAM-1 was noted. UVB also
      significantly augmented ICAM-1 induction by IL-1alpha and TNF-alpha. VCAM-1 was
      induced by stimulating HDMEC with IL-1alpha following a UVB irradiation dose of
      100 mJ/cm2. Flow cytometric analysis of the HDMEC stimulated with IL-1alpha for
      24h demonstrated that 12% of the cells expressed VCAM-1 but either IL-1alpha or
      UVB irradiation alone failed to induce VCAM-1 expression. Enhancement of T cell
      HDMEC binding by IL-1alpha or TNF-alpha treatment was not significantly affected
      after UVB irradiation. This study demonstrated that UVB irradiation can alter
      ICAM-1 and VCAM-1 expression on the HDMEC surface and that augmentation of ICAM-1
      expression and the IL-1alpha-dependent induction of VCAM-1 following UVB exposure
      might be important steps in the pathogenesis of sunburn.

PMID- 11971211
TI  - Therapeutic outcome of Epstein-Barr virus positive T/NK cell lymphoma in the
      upper aerodigestive tract.
AB  - Expression of the natural killer (NK) cell antigen CD56 is uncommon in malignant
      lymphoma, but when it is, it is almost exclusively of the non-B cell lineage and
      show a preference for the nasal and nasopharyngeal region. T/NK cell lymphoma is
      known to be aggressive and refractory to treatment. It is highly associated with
      the Epstein-Barr Virus (EBV), but clinical investigations are rarely reported,
      that is until recently. We report here, on the clinical features and therapeutic
      outcomes of patients with T/NK cell lymphomas and its association with EBV. We
      reviewed fifty-four cases with peripheral T cell lymphomas in the upper
      aerodigestive tract between Jan. 1987 and Aug. 1998 from the Severance Hospital,
      Yonsei University College of Medicine. The diagnosis of T/NK cell lymphoma was
      made according to the expression of the NK cell markers, CD56 antigen and
      cytoplasmic CD3epsilon, in tumor specimens, by immunohistochemistry. Epstein-Barr
      early region (EBER) RNA was detected using in situ hybridization on paraffin
      embedded sections. Among the 54 cases with malignant lymphomas occurring in the
      upper aerodigestive tract, 20 had T/NK cell lymphoma (37%). The primary sites of
      T/NK cell lymphomas were the nasal cavity, 12 cases (60%), the tonsils, 4 cases
      (20%), the nasopharynx, 2 cases (10%), and the oropharynx, 2 case (10%). There
      were no differences between the features, at diagnosis or therapeutic modalities
      for patients with T/NK cell lymphoma and non-T/NK cell lymphoma. The complete
      remission rate of T/NK cell lymphomas was lower than non-T/NK cell lymphomas (65%
      vs 85%, p=0.02). The overall survival of T/NK cell lymphomas was 13 months (1-74
      month), which was significantly lower than non-T/NK cell lymphomas [60.6% with a
      median follow up of 22 months (1-101 month, p=0.02)]. Disease free survival of
      T/NK cell lymphomas was 22 months (4-66 month), significantly lower than non-T/NK
      cell lymphomas [73.8% with a median follow up of 22 months (2-95 month), p=0.04].
      The overall survival rates for T/NK cell lymphomas were significantly lower than
      for EBV positive non-T/NK cell lymphomas (p=0.018). EBER RNA was detected in the
      paraffin-embedded tissue sections of all T/NK cell lymphomas, compared to only
      17.6% (6 of 34 cases) for non- T/NK cell lymphomas. In conclusion, as patients
      with T/NK cell lymphomas showed poor clinical outcomes, and a high association
      with EBV positivity, clinical trials with more investigational therapeutic
      strategies, and further research into the relationship of EBV infection with
      pathogenesis of T/NK cell lymphoma is warranted.

PMID- 11971212
TI  - Inducible nitric oxide synthase (iNOS) expression is increased in
      lipopolysaccharide (LPS)-stimulated diabetic rat glomeruli: effect of ACE
      inhibitor and angiotensin II receptor blocker.
AB  - Previously, we reported that high glucose enhanced cytokine-induced nitric oxide
      (NO) production by rat mesangial cells (MCs), and that the enhanced expression of
      the iNOS pathway may promote extracellular matrix accumulation by MCs. The
      present study was designed to examine whether the iNOS pathway is pathologically
      altered in experimental diabetic nephropathy, and whether therapy with
      angiotensin converting enzyme (ACE) inhibitor (imidapril: I) or angiotensin II
      type I receptor (AT1) blocker (L-158,809: L), ameliorates these changes. Male
      Sprague-Dawley rats were injected with diluent (control: C) or streptozotocin. At
      sacrifice after 4, 8 and 12 weeks, rats underwent either a 4 hour placebo or an
      intraperitoneal lipopolysaccharide (LPS, 2 mg/kg) challenge. Systolic blood
      pressure (SBP) and urinary protein excretion (UPE) increased significantly in
      diabetic (D) rats compared with C. The basal expression of glomerular iNOS mRNA
      was increased in D rats compared with that of C rats, by reverse- transcription
      (RT)-polymerase chain reaction (PCR), whereas there was no significant difference
      in the level of protein by Western blot analysis. Upon LPS stimulation, the iNOS
      mRNA and protein expression was significantly elevated in D rats. In D rats, this
      up-regulation, of LPS-stimulated iNOS expression, was equally ameliorated both by
      I and L in mRNA and protein levels. From immunohistochemistry (IHC), there was a
      negative staining for the iNOS within the glomeruli of five C rats without LPS
      treatment, but one of four rats, with LPS treatment, showed minimal iNOS staining
      in the glomeruli. In D rats, the glomerular mesangium and podocytes were positive
      for iNOS in each of three out of five rats with, and without, LPS treatment. In
      conclusion, LPS-stimulated glomerular iNOS expression was enhanced in diabetic
      pnephropathy, and the activation of angiotensin II may play a role in this
      enhancement.

PMID- 11971213
TI  - Behavior of fibroblasts on a porous hyaluronic acid incorporated collagen matrix.
AB  - A hyaluronic acid (HA) incorporated porous collagen matrix was fabricated at -70
      degrees C by lyophilization. The HA incorporated collagen matrix showed increased
      pore size in comparison with collagen matrix. Biodegradability and mechanical
      properties of matrices were controllable by varying the ultraviolet (UV)
      irradiation time for cross-linking collagen molecules. Addition of HA to collagen
      matrix did not effect ultimate tensile stress after UV irradiation. HA
      incorporated collagen matrices demonstrated a higher resistance against the
      collagenase degradation than collagen matrix. In an in vitro investigation of
      cellular behavior using dermal fibroblasts on the porous matrix, HA incorporated
      collagen matrix induced increased dermal fibroblast migration and proliferation
      in comparison with collagen matrix. These results suggest that the HA
      incorporated collagen porous matrix assumes to enhance dermal fibroblast
      adaptation and regenerative potential.

PMID- 11971214
TI  - Autoantibody against, malondialdehyde-modified low density lipoprotein in
      patients with non-diabetic unstable angina: a potential role in immunologic
      reaction of plaque instability.
AB  - The role of autoantibody against oxidized low-density lipoprotein (LDL) in the
      pathogenesis of atherosclerosis is still unknown. The purpose of this study was
      to determine whether autoantibodies against malondialdehyde (MDA)-modified LDL
      are associated with coronary artery disease (CAD) and clinical presentations of
      CAD in non-diabetic patients without acute myocardial infarction (AMI). We
      determined the serum levels of autoantibody against MDA-modified LDL by ELISA in
      71 patients with angiographically significant CAD (> or = 50% diameter stenosis
      in at least 1 vessel) and 80 controls without angiographically significant CAD.
      Among the total 151 subjects, 30 subjects did not have any clinical ischemic
      event, 90 subjects had stable angina symptoms, and 31 subjects had unstable
      angina symptoms. The autoantibody titer, expressed mean optical density units,
      was significantly higher in patients with CAD than in controls (0.177 +/- 0.014
      versus 0.127 +/- 0.011, respectively; p=0.006) and higher in unstable angina
      group than in stable angina group (0.240 +/- 0.025 versus 0.145 +/- 0.007,
      respectively; p < 0.001). By logistic regression analysis, the high autoantibody
      titer was associated significantly with CAD (P=0.008), independent of age,
      gender, body mass index, triglyceride concentration, and the ratio of total
      cholesterol-high density lipoprotein (HDL) cholesterol. In multiple regression
      analysis, presence of CAD, smoking history and low HDL-cholesterol level were
      independent factors associated with a increased anti-oxLDL Ab titer. The
      autoantibody titer was significantly lower in nonsmoker than smoker (p=0.019) and
      higher in low HDL- cholesterol (< or = 35 mg/dl) group than in high HDL
      cholesterol group (p=0.012). Elevated autoantibody titer was associated with CAD
      and the unstable clinical presentation of CAD. Our results suggest that immune
      response to oxidized LDL may play a role in the pathogenesis of atherosclerosis
      and plaque instability.

PMID- 11971215
TI  - Significance of 99mTc-ECD SPECT in acute and subacute ischemic stroke: comparison
      with MR images including diffusion and perfusion weighted images.
AB  - 99mTc-ECD SPECT is valuable for the evaluation of cell viability and function.
      The purpose of the present study was to evaluate the significance of 99mTc-ECD
      brain SPECT in ischemic stroke. We compared 99mTc-ECD brain SPECT with perfusion
      and diffusion weighted images (PWI, DWI). Ten patients with acute and early
      subacute ischemic stroke were included in this prospective study. T2-weighted
      images (T2WI), DWI, PWI and 99mTc-ECD SPECT were obtained during both the
      acute/early subacute and late subacute stages. In the case of PWI, time to peak
      (TTP) and regional cerebral blood volume (rCBV) maps were obtained. The rCBV map
      and 99mTc-ECD SPECT images were compared in 8 lesions using DeltaAI. The
      asymmetry index (AI) was calculated as (Ci - Cc) X 200 / (Ci + Cc); where Ci is
      the mean number of pixel counts of an ipsilateral lesion and Cc is the mean
      number of pixel counts of the normal contralateral hemisphere. DeltaAI was
      defined as AIacute - AIsubacute in the ischemic core and periphery. PWI and 99mTc
      ECD SPECT detected new lesions of the hyperacute stage or of evolving stroke more
      accurately than T2WI and DWI. 99mTc-ECD SPECT was able to localize the infarct
      core and peri-infarct ischemia in all lesions in both the acute and the subacute
      stages. DeltaAI was higher in the rCBV map than in the 99mTc-ECD SPECT images in
      the ischemic core (p = 0.063) and in the periphery (p = 0.091). In the 99mTc-ECD
      SPECT images, DeltaAI was higher in the ischemic core than in the periphery (p =
      0.028). During the subacute stage, 99mTc-ECD SPECT detected all the lesions
      without the pseudonormalization seen in the MR images of 5/11 lesions. Based on
      this study, 99mTc-ECD SPECT is comparable to PWI in terms of its ability to
      detect acute stroke and is more useful than PWI in the case of subacute
      infarction.

PMID- 11971216
TI  - Clinical significance of depressed-type colorectal neoplasms based on growth and
      development.
AB  - A route of colorectal cancer development other than the adenoma-carcinoma
      sequence has recently become an issue due to the discovery of depressed-type
      early colorectal cancers. Moreover, the fact that some polyp-like cancers
      actually originate from depressed-type lesions has become obvious. Despite the
      protruding shapes of depressed-type early colorectal cancers, they probably have
      biological characteristics, which are different from those of the usual polyp
      lesions. We undertook this study to evaluate the clinical significance of
      depressed-type colorectal neoplasms. The authors recently experienced 87 cases of
      depressed-type colorectal neoplasms. Using Kudo's classification, we classified
      these 87 cases into three types based on their growth patterns, type IIc, type
      IIa + IIc, and type Is + IIc, and then analyzed these types on the basis of size,
      type, and submucosal invasion rate. The submucosal invasion rate of cancers of
      type IIa + IIc was significantly higher than that of type IIc (p < 0.05), and the
      rate for cancers of types IIa + IIc and Is + IIc together was significantly
      higher than that of type IIc (p < 0.05). However, no significant difference was
      found between the rates of types IIa + IIc and Is + IIc. In conclusion, the IIa +
      IIc and Is + IIc sub-types of depressed-type colorectal neoplasms, individually
      and together, have higher rates of submucosal invasion than type IIc lesions.
      Accordingly, type IIa + IIc and type Is + IIc must be differentiated from the
      usual polyps and should be managed cautiously, despite their protruding shapes.

PMID- 11971217
TI  - H2O2 enhances Ca2+ release from osteoblast internal stores.
AB  - The physiological activity of osteoblasts is known to be closely related to
      increased intracellular Ca2+ activity ([Ca2+]i) in osteoblasts. The cellular
      regulation of [Ca2+]i in osteoblasts is mediated by Ca2+ movements associated
      with Ca2+ release from intracellular Ca2+ stores, and transmembrane Ca2+ influx
      via Na+-Ca2+ exchanger, and Ca2+ ATPase. Reactive oxygen species, such as H2O2,
      play an important role in the regulation of cellular functions, and act as
      signaling molecules or toxins in cells. In this study, we investigated the
      effects of H2O2 on cellular Ca2+ regulation in osteoblasts by measuring
      intracellular Ca2+ activities using cellular calcium imaging techniques.
      Osteoblasts were isolated from the femurs and tibias of neonatal rats, and
      cultured for 7 days. The cultured osteoblasts were loaded with a Ca2+-sensitive
      fluorescent dye, Fura-2, and fluorescence images were monitored using a cooled
      CCD camera, and subsequently analyzed using image analyzing software. The results
      obtained are as follows: (1) The osteoblasts with lower basal Ca2+ activities
      yielded a transient Ca2+ increase, a Ca2+ spike, while osteoblasts with higher
      basal Ca2+ activities showed a continuous increase in [Ca2+]i leading to cell
      death. (2) Ca2+ spikes, generated after removing Na+ from superfusing solutions,
      were blocked by H2O2 and this was followed by a sustained increase in Ca2+
      activity. (3) ATP- induced Ca2+ spikes were inhibited by pretreating with H2O2
      and this was followed by a continuous increase of [Ca2+]i. When cells were
      pretreated with the exogenous nitric oxide (NO) donor S-Nitroso-N
      acetylpenicilance (SNAP, 50 microM), treatments of ATP (1 mM) induced a Ca2+
      spike-like increase, but [Ca2+]i did not return to the basal level. (4) The
      expression of inositol- 1,4,5-triphosphate receptor (IP3R) was enhanced by H2O2.
      Our results suggest that H2O2 modulates intracellular Ca2+ activity in
      osteoblasts by increasing Ca2+ release from the intracellular Ca2+ stores.

PMID- 11971218
TI  - Comparative study of concentration of isoflavones and lignans in plasma and
      prostatic tissues of normal control and benign prostatic hyperplasia.
AB  - OBJECTIVE: Isoflavones and lignans are phytoestrogens that have recently gained
      interest as dietary factors related to prostatic diseases. However, no data on
      the concentrations in prostate tissue in humans is available. Therefore, the
      concentrations of isoflavones and lignans in plasma and prostatic tissues
      according to the prostate volume were compared to determine their possible effect
      on the benign prostatic growth. METHODS: Fasting plasma and prostatic tissue
      specimens were acquired from 25 men over 50 years of age with similar normal
      dietary habits and no previous history of drug intake that could affect the
      isoflavones and lignans levels. The tissue was acquired either during a
      transurethral resection of the prostate in 15 patients with benign prostatic
      hyperplasia (BPH) with prostate volume over 40 ml or during a radical
      cystoprostatectomy in 10 patients with bladder cancer with a prostate volume < 25
      ml, who were used as the controls. Quantitative analysis of the isoflavones,
      specifically equol, daidzein and genistein and lignans, particularly enterodiol
      and enterolactone, was performed by gas chromatography-mass spectrometry.
      RESULTS: The mean prostatic concentrations of enterodiol, enterolactone, equol
      and daidzein in the BPH and the control groups were similar. However, the mean
      prostatic concentration of genistein was significantly lower in the BPH group
      than in the control group (65.43 +/- 17.05 vs 86.96 +/- 37.75 ng/ ml,
      respectively, p=0.032). The plasma concentration of isoflavones and lignans in
      the two groups were comparable. CONCLUSION: Isoflavones, but not lignans, have
      some influence the benign prostatic growth, and the prostatic concentration of
      genistein possibly has the closest association among them. More studies to
      further clarify the roles and mechanisms of isoflavone action on BPH including
      pharmacokinetic studies are recommended.

PMID- 11971219
TI  - Local delivery of nitric oxide from an eluting stent to inhibit neointimal
      thickening in a porcine coronary injury model.
AB  - To assess the effect of a NO-eluting stent on reducing neointimal thickening in a
      porcine coronary artery stent injury model, sodium nitroprusside (SNP), a NO
      donor, was incorporated into polyurethane (PU) polymer and coated onto metallic
      coil stents, and two types of stents with thin and thick barrier coatings were
      characterized. In vivo biological activity of the NO-eluting stents was assessed
      by measurement of coronary arterial cGMP levels in 32 pigs/64 arteries at days 1,
      2, 7 and 14. Morphometric analyses were performed in 16 pigs to determine the
      effect of NO-eluting stents on neointimal hyperplasia 28 days following arterial
      injury. The SNP-coated stents released NO in a controlled manner for up to 4
      weeks in the in vitro experiments and an increase in local tissue cGMP levels was
      demonstrated for up to 14 days. The neointimal area at 28 days was not
      diminished, however, by NO eluded from either stents of thin or thick barriers
      (control bare stent - 0.66 mm2, control PU stent - 0.68 mm2, SNP-PU thin coating
      stent - 0.78 mm2, SNP-PU thick coating stent - 0.85 mm2; all p=NS). In
      conclusion, the SNP-coated polymer stent exerted a local biological effect on the
      arterial wall, with sustained elevation of cGMP level. Although local delivery of
      NO from this device did not reduce neointimal hyperplasia in this porcine model,
      this polymer-coated stent might be a promising tool for administration of other
      agents that may modify the reparative tissue responses leading to restenosis.

PMID- 11971220
TI  - Fetal reduction in multifetal pregnancy--ethical dilemmas.
AB  - As a result of the increased use of drugs that enhance fertility, and the advent
      of in vitro fertilization and embryo transfer over the last 2 decades, the
      incidence of multifetal pregnancies has increased exponentially. In parallel with
      this increase methods of care for women carrying multiple fetuses have become
      more complex and well developed. Importantly, it has become obvious that in the
      case of such pregnancies the rates of mortality and morbidity of both fetuses and
      mothers, particularly in cases where four or more fetuses are involved, are
      extremely high. Improvements in the techniques of assisted fertilization should
      result in fewer iatrogenic multifetal pregnancies and a commensurate decrease in
      related risks. Fetal reduction seems to be an acceptable method of improving
      maternal and fetal outcome in high order multiple pregnancies despite the many
      unresolved medical and ethical dilemmas.

PMID- 11971221
TI  - Proteus syndrome: a natural clinical course of Proteus syndrome.
AB  - A 16-year-old Korean male patient presented with macrodactyly, hemihypertrophy of
      the face and extremities, plantar cerebriform hyperplasia, a subcutaneous mass of
      the left chest, macrocephaly and verrucous epidermal nevi. These findings are
      consistent with Proteus Syndrome. The clinical features, etiology, management,
      natural course and differential diagnosis of this case are discussed.

PMID- 11971222
TI  - Successful cyclophosphamide therapy in recurrent eosinophilic colitis associated
      with hypereosinophilic syndrome.
AB  - Eosinophilic colitis is a relatively rare complication of hypereosinophilic
      syndrome which is characterized by abdominal pain and bloody diarrhea and is
      usually treated with steroids and hydroxyurea. However, no standard regimen
      exists in cases of intractable disease despite several treatment attempts with
      Interferon-alpha, cyclosporin, etoposide, and vincristine, etc. We here report a
      case of a 43-year-old woman with recurrent eosinophilic colitis as a complication
      of hypereosinophilic syndrome who was successfully treated with cyclophosphamide.

PMID- 11971223
TI  - Incidentally found pharyngoesophageal diverticulum on ultrasonography.
AB  - The pharyngoesophageal diverticulum in the lower part of the neck can be detected
      using neck ultrasonography. We present a case of pharyngoesophageal diverticulum
      mimicking a thyroid nodule, which was found incidentally by ultrasonography, and
      discuss its peculiar findings, which might be useful to diagnose
      pharyngoesophageal diverticulum and to prevent invasive procedures such as needle
      aspiration biopsy.

PMID- 11971224
TI  - Successful treatment of pure red cell aplasia with plasmapheresis in a patient
      with systemic lupus erythematosus.
AB  - Pure red cell aplasia (PRCA) is a rare cause of anemia associated with systemic
      lupus erythematosus (SLE), and fewer than 20 cases have been reported. The
      development of PRCA may be mediated by an autoimmune mechanism which is supported
      by the presence of antibodies that impair various stages and mechanisms of
      erythropoiesis, by the association with immunological disorders or lymphoma, and
      by a favorable response to immunosuppressive drugs, antilymphocyte globulin,
      thymectomy, and splenectomy. However, these therapies have not been successful in
      all patients with PRCA. We report our experience with a 31-year-old female
      patient with SLE who developed PRCA that did not respond to immunosuppressive
      therapies. However, complete normalization of erythropoiesis was achieved after
      the removal of the autoantibodies by plasmapheresis, and the patient has now
      maintained a normal hemoglobin level for more than eight months. We suggest that
      plasmapheresis might be tried in the treatment of PRCA cases before other more
      aggressive therapies are commenced.

PMID- 11971225
TI  - Descemet's membrane detachment associated with inadvertent viscoelastic injection
      in viscocanalostomy.
AB  - We report a case of Descemet's membrane detachment, a rare complication of
      viscocanalostomy. During the operation, the injection cannula was directed
      slightly oblique to the Schlemm's canal rather than parallel to it. Localized
      corneal whitening developed adjacent to the injection site during viscoelastic
      injection. One week postoperatively, corneal edema decreased and Descemet's
      membrane detachment was noted. Nine months after surgery, the cornea was clear
      while the Descemet's membrane detachment remained. And IOP was 19 mmHg without
      any medications. We think that improper cannula positioning during viscoelastic
      injection may cause Descemet's membrane detachment, a rare complication of
      viscocanalostomy.

PMID- 11971226
TI  - VIII Ibero American Congress of Cell Biology and the 1st Congress of the Peruvian
      Society of Cell Biology. September 24-26, 2001, Lima, Peru. Abstracts.

PMID- 11971227
TI  - Biology of NK cells. A Festschrift in Honor of Andrei Sulica.

PMID- 11971228
TI  - Lysosomal storage diseases. Fabry disease: new insights and future perspectives.
      Proceedings and abstracts of an international symposium. Seville, April 2001.

PMID- 11971229
TI  - Practical considerations in dealing with embryos. Proceedings of the Satellite
      Symposium of the International Embryo Transfer Society. January 16, 2002. Foz Do
      Iguassu, Brazil.

PMID- 11971230
TI  - [Proceedings of Workshop on Biosignal Processing. 16-17 July 1998. Munich,
      Germany].

PMID- 11971231
TI  - [Guidelines for clinical practice: ovarian cysts].

PMID- 11971232
TI  - Feedback without fear.

PMID- 11971233
TI  - Abstracts of the XXth International Conference on Yeast Genetics and Molecular
      Biology. August, 2001. Prague, Czech Republic.

PMID- 11971234
TI  - Immunology and aging in Europe. Proceeding of the 2nd Conference on Basic Biology
      and Clinical Impact of Immunosenescence. March 22-26, 2001. Cordoba, Spain.

PMID- 11971235
TI  - The various aspects of qualitative research.

PMID- 11971236
TI  - Kava concerns. FDA, Botanical Council raises safety concerns.

PMID- 11971237
TI  - [In vitro evaluation of the mechanical effects of sensitive toothpastes of the
      Swiss market].
AB  - "Sensitive pastes" are advertised for use by patients suffering from dentin
      hypersensitivity. Their market share is growing. Their potential of adverse
      mechanical side effects on dentin are consequently of concern. The aim of this
      study was to assess the cleaning efficiency, the relative dentin abrasion and the
      surface roughness induced by ten sensitive toothpastes of the Swiss market.
      Cleaning efficiency was assessed planimetrically, the relative dentin abrasion
      was measured using a radio tracer method and the surface roughness was
      established using a surface scanning method. Four out of the ten tested sensitive
      toothpastes produced only low abrasion and surface roughening on dentin, and are
      consequently suitable for the use by patients with dentin hypersensitivity. The
      remaining six pastes are too aggressive to warrant unlimited use on exposed
      dentin surfaces. The pain relieving effect of active ingredients of the
      toothpastes was not assessed.

PMID- 11971239
TI  - CHI slams 'constant pressure on staff'.

PMID- 11971238
TI  - Director of nursing not fit to fight bullying culture.

PMID- 11971240
TI  - A word from the wise.

PMID- 11971241
TI  - Devolution not revolution.

PMID- 11971242
TI  - Allied forces.

PMID- 11971243
TI  - Multiple choice. Interview by Charlotte Alderman.

PMID- 11971244
TI  - Cover story. Interview by Mary Hampshire.

PMID- 11971246
TI  - A travellers tale.

PMID- 11971245
TI  - Endangered specialty.

PMID- 11971247
TI  - Dark thoughts.

PMID- 11971248
TI  - Not the response we need to head lice concerns.

PMID- 11971250
TI  - Responsive assessment of clinical competence: Part 2.
AB  - AIM: To highlight the concerns that students and practitioners might have about
      the process of assessment of their nursing practice, and to suggest an
      alternative method. METHOD: Questionnaires were given to 300 student nurses and
      155 nurse practitioners throughout a Common Foundation Programme and interviews
      were conducted with 70 students and 80 assessors from three colleges of nursing.
      RESULTS: Although students generally favoured structured assessment of their
      progress, they would like some flexibility. Students acknowledged stress caused
      by continuous assessment. Assessment of clinical competence was seen to be as
      important as academic assessment. It was felt that time should be allowed to
      discuss progress during and after practical experience. Students appreciated the
      need for continuous assessment, but favoured a change in the way assessment
      booklets were used. CONCLUSION: The author suggests a new concept of continuous
      assessment of students of nursing clinical competence. This new model is called
      responsive assessment, in which the assessment process focuses on the worth and
      merit of the care given by students to clients/patients, as well as set learning
      objectives.

PMID- 11971249
TI  - Declining asthma severity.
AB  - An overview of the factors affecting the declining severity of asthma.

PMID- 11971251
TI  - Trust ignored patient care concerns.

PMID- 11971252
TI  - Introducing nurse telephone triage into primary care.
AB  - In this article, the authors describe the changes required to introduce a nurse
      telephone triage system into a large primary care practice in York. 'Whole
      systems' changes were necessary in that not one element of the primary healthcare
      team (PHCT) system has remained unaffected. The introduction of nurse triage has
      changed working practices, professional working relationships and job
      satisfaction. Far from being just a workload management solution, it has
      fundamentally altered the way that nurses, doctors and reception staff work
      together and with patients.

PMID- 11971253
TI  - Men's health: a cause for concern.
AB  - The state of men's health is a cause for concern; men are less likely to seek
      medical help than women even though they are more likely to die at a younger age.
      Andrew Barton looks at the issues surrounding men's health by focusing on
      prostate and testicular cancer.

PMID- 11971254
TI  - RCN agrees timetable for Hancock's replacement.

PMID- 11971256
TI  - Red tape stops sick nurse seeing family.

PMID- 11971255
TI  - NHS bank 'not likely to cut costs'.

PMID- 11971257
TI  - Overseas staff complain of difficulties in registering.

PMID- 11971258
TI  - Nurses were 'unfeeling' claim grieving sisters.

PMID- 11971259
TI  - Demand for cash power in Scotland.

PMID- 11971260
TI  - Evidence for an attentional component of the perceptual misalignment between
      moving and flashing stimuli.
AB  - If a pair of dots, diametrically opposed to each other, is flashed in perfect
      alignment with another pair of dots rotating about the visual fixation point,
      most observers perceive the rotating dots as being ahead of the flashing dots
      (flash-lag effect). This psychophysical effect was first interpreted as the
      result of a perceptual extrapolation of the position of the moving dots. Also, it
      has been conceived as the result of differential visual latencies between
      flashing and moving stimuli, arising from purely sensory factors and/or
      expressing the contribution of attentional mechanisms as well. In a series of two
      experiments, we had observers judge the relative position between rotating and
      static dots at the moment a temporal marker was presented in the visual field. In
      experiment 1 we manipulated the nature of the temporal marker used to prompt the
      alignment judgment. This resulted in three main findings: (i) the flash-lag
      effect was observed to depend on the visual eccentricity of the flashing dots;
      (ii) the magnitude of the flash-lag effect was not dependent on the offset of the
      flashing dot; and (iii) the moving stimulus, when suddenly turned off, was
      perceived as lagging behind its disappearance location. Taken altogether, these
      results suggest that neither visible persistence nor motion extrapolation can
      account for the perceptual flash-lag phenomenon. The participation of attentional
      mechanisms was investigated in experiment 2, where the magnitude of the flash-lag
      effect was measured under both higher and lower predictability of the location of
      the flashing dot. Since the magnitude of the flash-lag effect significantly
      increased with decreasing predictability, we conclude that the observer's
      attentional set can modulate the differential latencies determining this
      perceptual effect. The flash-lag phenomenon can thus be conceived as arising from
      differential visual latencies which are determined not only by the physical
      attributes of the stimulus, such as its luminance or eccentricity, but also by
      attentional mechanisms influencing the delays involved in the perceptual
      processing.

PMID- 11971261
TI  - Bibliography. Current world literature. Hematpopietic growth factors.

PMID- 11971262
TI  - Enhanced bacterial virulence through exploitation of host glycosaminoglycans.
AB  - Present in the extracellular matrix and membranes of virtually all animal cells,
      proteoglycans (PGs) are among the first host macromolecules encountered by
      infectious agents. Because of their wide distribution and direct accessibility,
      it is not surprising that pathogenic bacteria have evolved mechanisms to exploit
      PGs for their own purposes, including mediating attachment to target cells. This
      is achieved through the expression of adhesins that recognize glycosaminoglycans
      (GAGs) linked to the core protein of PGs. Some pathogens, such as Bordetella
      pertussis and Chlamydia trachomatis, may express more than one GAG-binding
      adhesin. Bacterial interactions with PGs may also facilitate cell invasion or
      systemic dissemination, as observed for Neisseria gonorrhoeae and Mycobacterium
      tuberculosis respectively. More-over, pathogenic bacteria can use PGs to enhance
      their virulence via a shedding of PGs that leads to there lease of effectors that
      weaken the host defences. The exploitation of PGs by pathogenic bacteria is thus
      a multifaceted mechanistic process directly related to the potential virulence of
      a number of microorganisms.

PMID- 11971263
TI  - A distinctive single-strand DNA-binding protein from the Archaeon Sulfolobus
      solfataricus.
AB  - Single-stranded DNA binding proteins (SSBs) have been identified in all three
      domains of life. Here, we report the identification of a novel crenarchaeal SSB
      protein that is distinctly different from its euryarchaeal counterparts. Rather
      than comprising four DNA-binding domains and a zinc-finger motif within a single
      polypeptide of 645 amino acids, as for Methanococcus jannaschii, the Sulfolobus
      solfataricus SSB protein (SsoSSB) has a single DNA-binding domain in a
      polypeptide of just 148 amino acids with a eubacterial-like acidic C-terminus.
      SsoSSB protein was purified to homogeneity and found to form tetramers in
      solution, suggesting a quaternary structure analogous to that of E. coli SSB
      protein,despite possessing DNA-binding domains more similar to those of
      eukaryotic Replication Protein A (RPA). We demonstrate distributive binding of
      SsoSSB to ssDNA at high temperature with an apparent site size of approximately
      five nucleotides (nt)per monomer. Additionally, the protein is functional both in
      vitro and in vivo, stimulating RecA protein-mediated DNA strand-exchange and
      rescuing the ssb-1 lethal mutation of E. coli respectively. We discuss possible
      evolutionary relationships amongst the various members of the SSB/RPA family.

PMID- 11971264
TI  - Regulation of transcription by the activity of the Shigella flexneri type III
      secretion apparatus.
AB  - The virulence plasmid-encoded type III secretion system of Shigella flexneri
      consists of the Mxi-Spa secretion apparatus, secreted proteins IpaA-D and IpgD
      involved in entry of bacteria into epithelial cells,cytoplasmic chaperones IpgC
      and IpgE and 15 other secreted proteins of unknown function, including VirA and
      members of the IpaH family. The activity of the Mxi-Spa apparatus is regulated by
      external signals, and transcription of virA and IpaH genes is specifically
      induced in conditions of active secretion. We present genetic evidence that
      regulation of these genes involves both MxiE, the transcriptional activator of
      the AraC family encoded by the mxi operon, and IpgC, the chaperone for IpaB and
      IpaC. We also show that together MxiE and IpgC are sufficient to activatevirA and
      IpaH 9.8 promoters in Escherichia coli. InS. flexneri, increasing the expression
      of IpgC led to a concomitant increase in IpaH production in conditions of non
      secretion. This suggests that the activity of secretion is sensed by the presence
      of free IpgC, which acts as a coactivator to allow MxiE to activate transcription
      at its target promoters.

PMID- 11971265
TI  - Abstracts of the Annual Meeting of the Japanese Society of Plant Physiologists.
      Okayama, Japan, March 28-30, 2002.

PMID- 11971266
TI  - American Academy of Neurology 54th Annual Meeting. Denver, Colorado, April 13-20,
      2002. Abstracts.

PMID- 11971267
TI  - Bibliography. Current world literature. Upper airway disease.

PMID- 11971268
TI  - Bibliography. Current world literature. Mechanisms in allergy and adult asthma.

PMID- 11971269
TI  - Bibliography. Current world literature. HIV infection and AIDS.

PMID- 11971270
TI  - Bibliography. Current world literature. Sexually transmitted diseases and urinary
      tract infections.

PMID- 11971271
TI  - Twin-endoscope scissors resection (T-ESR): a new minimally invasive technique for
      performing colonic mucosectomy.
AB  - BACKGROUND: Piecemeal resection is currently the safest method for the endoscopic
      removal of large sessile colonic polyps. However, this method has its
      limitations, including the quality of the specimen received for histopathology
      and the need for early follow-up due to the possibility of incomplete resection
      and recurrence. New methods enabling en bloc resection would be advantageous in
      these respects. METHODS: We developed a new technique that uses endoscopic
      scissors and two endoscopes to perform mucosal resection in a porcine model. So
      far, the technique has been evaluated in two animals. RESULTS: The resection of
      intact mucosal specimens measuring 1.5 x 1 cm and 2.2 x 3.5 cm was achieved, with
      no procedural or late hemorrhage and no clinical or radiological evidence of
      perforation. CONCLUSION: After further development and evaluation, this technique
      should be suitable for the resection of large sessile colonic polyps in humans.

PMID- 11971272
TI  - Germany adds high-throughput PTP to its national genotyping platform.

PMID- 11971274
TI  - 86th Meeting of the German Society of Pathology. 3-6 April 2002, Vienna, Austria.
      Abstracts.

PMID- 11971273
TI  - Can genes predict effectiveness of hypertension drugs?

PMID- 11971275
TI  - IX International Workshop on CLL. 14-16 September 2001, San Diego, California,
      USA. Abstracts.

PMID- 11971276
TI  - Current world literature. Tropical and travel-associated diseases.

PMID- 11971277
TI  - Current world literature. Gastrointestinal infections.

PMID- 11971279
TI  - Current world literature. Antimicrobial agents: parasitic/viral.

PMID- 11971278
TI  - Current world literature. Antimicrobial agents: bacterial/fungal.

PMID- 11971280
TI  - Genetic effects of space hadrons on bacteriophage under Alpine conditions.
AB  - A dried film culture of bacteriophage T4Br + was kept in a lead bioblock for 366
      days under Alpine conditions at an altitude of 6100 m above sea level to study
      the genetic effect of space hadrons. In the gelatin-like film under study we
      discovered some film plots with markedly reduced bacteriophage survival. In such
      plots, the mutation frequency exceeded the spontaneous background mutation rate
      60-100 times. The spectrum of r mutations as classified into standard groups rI,
      rII and rIII differed from that found for other model radiation systems such as
      gamma-ray radiation in buffer or nutrient broth, and hadron and HZE particle
      radiation under space flight conditions. Reversion analysis of 159 rII mutants
      showed that 54.4% had small and elongated deletions, 23.16% had point mutations,
      and 22.5% of all the mutants had both small deletion and point mutations.

PMID- 11971281
TI  - Physiological aspects of automatic physical training control by biofeedback in
      weightlessness.
AB  - An automatically regulated biofeedback apparatus "UN-1" is described for enabling
      astronauts to maintain specified levels of exercise or lower body negative
      pressure within acceptable limits of cardiac function. The apparatus was also
      used to assess the workload tolerance of cosmonauts during space flight. Under
      these conditions the cosmonaut was unable to exercise on the cycloergometer when
      his heart rate reached 140 beats/minute steady state.

PMID- 11971282
TI  - Physiological reactions during acute adaptation to reduced gravity.
AB  - Experiments were carried out on healthy volunteers exposed to a 7-day water
      immersion. The subjects were kept dry by use of a water proof, highly elastic
      cloth. During the experiment different cardiovascular, fluid-electrolyte and
      biochemical parameters were recorded. During the 7-day immersion, physiological
      parameters changed on a phasic basis. An acute period of adaptation began within
      the first minutes of immersion and ended by the third day. Later some of the
      parameters showed relative normalization. The experimental results suggest that
      the hypophyseal-adrenal system and renal function are closely coupled regulatory
      mechanisms for adaptive reactions of the cardiovascular system and for fluid
      electrolyte metabolism during acute adaptation of the human body to reduced
      gravity.

PMID- 11971283
TI  - Variations in the recombination rate of Drosophila melanogaster induced by
      balloon flight.
AB  - Drosophila males, heterozygous for b, pr, cn and en genes, were submitted to
      balloon flights, ceiling time ranging from about 8 hours (flights performed in
      France) to 22 hours (transmediterranean flight). Effects on recombination were
      investigated on progeny after breeding with females homozygous for the same
      genes. The transmediterranean flight and one flight performed in France resulted
      in a significantly higher recombination rate.

PMID- 11971284
TI  - Gravity and land plant evolution: experimental induction of lignification by
      simulated hypergravity and water stress.
AB  - The ability to lignify cell walls has long been associated with the upright
      condition and sometimes massive body of the land plant, and gravitational
      regulation of lignification has been demonstrated by clinostat/centrifuge
      techniques. Previous centrifuge experiments were conducted using plants in the
      early stages of growth, hence already programmed for immediate lignification.
      Elodea, an aquatic Angiosperm long believed to be incapable of lignification
      synthesizes lignin or lignin-like phenolics during 6 days incubation at 80 g .
      Yields in some cases exceeded stationary controls by as much as 300%. Supporting
      data were obtained using bean cotyledons. Exposure to 80 g induced lignification
      in extra-vascular tissue along with vascular lignin deposits. The loss of a
      buoyant medium also deprived early land plants of unlimited water: the lignin
      content in cucumber seedlings grown in water is reduced 50% or more relative to
      pot grown plants but water stress elevates lignin content as much as 100%. This
      suggests that the water status of the land environment may have provided a
      "backup" or "reinforcement" signal for an adaptive axial support system.

PMID- 11971285
TI  - Biological studies of Chlorella pyrenoidosa (strain LARG-1) cultures grown under
      space flight conditions.
AB  - This paper reports data from an electron microscopic analysis of Chlorella
      pyrenoidosa (LARG-1) cultures after five days of growth in the dark on a
      semiliquid mineral/glucose medium in the IFS-2 device on board the Soyuz 27
      Salyut 6-Soyuz 28 orbital research complex (Soviet-Czechoslovak experiment
      "Chlorella-1"). For space flight of five days duration the ultrastructural
      cellular organization of the flight and control cultures were similar. This
      testifies to normal cell function.

PMID- 11971286
TI  - Development of higher fungi under weightlessness.
AB  - The development of Polyporus brumalis basidomycete cultures, both in the dark and
      in the light, was studied in the 17 day experiment on the orbital station Salyut
      5 and in the 20 day experiment on the orbital station Salyut 6. In the first
      experiment the test tube cultures were exposed to weightlessness beginning from
      the stage of the fruiting body primordium. In the second experiment the culture
      was exposed in large containers at the stage of mycelium growth. In the first
      experiment fruiting bodies that had formed in light had stems and caps
      approximating the appearance and anatomical structure of the control culture. The
      fruiting bodies and caps were oriented towards the light. Some structural changes
      in the hymenophore were observed. Fruiting bodies developed in the dark had
      twisted stems and no caps. In the second experiment no fruiting bodies were
      formed in the dark. Light-optical and electron-microscopic studies of Polyporus
      brumalis growth under weightlessness were carried out.

PMID- 11971287
TI  - Growth and cell structure of Proteus vulgaris when cultivated in weightlessness
      in the Cytos apparatus.
AB  - Growth data and electron-microscopic analyses are presented for Proteus vulgaris
      cultures which were grown during space flight in polyethylene packets in a
      semisolid medium with Tryptose for 96 h. In the suboptimal culture conditions the
      growth and morphological characteristics of the flight and ground control
      variants were nearly identical, but we were able to detect a number of
      differences between the cellular ultrastructure of these variants. These
      differences testify to changes in the bacterial cell metabolism during space
      flight.

PMID- 11971288
TI  - [Etymology of clove].
AB  - A very brief history of clove in Europe and Indonesia with particular reference
      to Dutch monopoly of clove in the spice islands, the Moluccas, is presented. The
      etymology of clove originates from the Greek word karuophullon
      (karuon=nut+phullon=leaf) and the Latin word caryophyllon, which were transformed
      to clou de girofle in Old French and clow of gilofer in Middle English. Further
      modification resulted in a separation into clove and gilly-flower.

PMID- 11971289
TI  - [Rhubarb in the East and the West].
AB  - An etymological account of edible rhubards (stalks) and medicinal rhubarbs
      (rhizomes) is presented. Rheum rhaponticum (edible) was originally brought to the
      West from the barbarian Volga (old name Rha) district and from the Black Sea (old
      name Pontus) area. Rha comes from the Indo-European protolanguage *sreu, which
      means river or to flow. Rha barbarum was transformed to rhubarb in English and to
      Rhabarber in German. Medicinal rhubarbs are R. palmatum (the shape of its leaves
      are palm shaped), R. tanguticum from Tangut, China, and R. officinale and R.
      coreanum (both of which need no explanation). The relationship of Rheum with
      Rumex is also mentioned.

PMID- 11971290
TI  - [European paintings entitled "Jesus Christ as Pharmacist" in the Middle Ages and
      later].
AB  - Ninety-eight pictures painted in the Middle Ages and later entitled "Christ as
      Pharmacist" are shown in a little German book (W. H. Hein, Christus als
      Apotheker, Govi-Verlag, Frankfurt am Main, 1974). In the three paintings shown
      here, Christ appears as a pharmacist standing behind a pharmacy table used to
      compound medicine, and he has a medicinal balance in his left hand. The Christian
      terms, such as faith, love, and hope, and the drug's name are written on each of
      the drug vase labels. It seems that the purpose of displaying these paintings in
      a pharmacy was both to propagate Christianity to the poor who bought medicine at
      their family pharmacy and to win their respect for the pharmacist.

PMID- 11971291
TI  - Changing practices of commemoration in neurology: comparing Charcot's 1925 and
      1993 centennials.

PMID- 11971293
TI  - The First American and French commemorations in molecular biology: from
      collective memory to comparative history.

PMID- 11971292
TI  - Medicine and the culture of commemoration: representing Robert Koch's discovery
      of the tubercle bacillus.

PMID- 11971294
TI  - Claude Bernard and Louis Pasteur: contrasting images through public
      commemorations.

PMID- 11971295
TI  - Acclimatizing the world: a history of the paradigmatic colonial science.
AB  - This paper examines the institutions, personages, and the theories that informed
      acclimatization activities in nineteenth-century France, England, and the two
      colonies of Algeria and Australia. Treating acclimatization as a scientific
      concept and activity the essay begins with the conditions of its emergence in
      Enlightenment France. Subsequent sections trace the growth of the acclimatization
      movement and its translation to the British context, and consider reasons for its
      decline in the last third of the nineteenth century. Efforts are made to show why
      many perceived acclimatization to be the paradigmatic colonial science with
      applications as diverse as agriculture, settlement schemes, field sports, and
      human health. Emphasis falls on the French and British cultural spheres, as these
      were the dual epicenters of both modern colonialism and organized acclimatization
      activity.

PMID- 11971296
TI  - Pressure gauge.

PMID- 11971297
TI  - Guilty by association.

PMID- 11971298
TI  - Breathing space. Interview by Charlotte Alderman.

PMID- 11971299
TI  - Custody battle.

PMID- 11971301
TI  - On the couch....

PMID- 11971300
TI  - Danger signals.

PMID- 11971302
TI  - A rapid response.

PMID- 11971304
TI  - Cancer nursing education.

PMID- 11971305
TI  - Attempting to set up a randomised controlled trial.
AB  - AIM: The aim of this article is to provide an account of an attempt to set up a
      randomised control trial (RCT) to evaluate the effects of programmes of
      continuing professional education on nursing practice. METHOD: The logistical and
      methodological challenges of the RCT are described, and an alternative quasi
      experimental approach is outlined. RESULTS: It was not possible to obtain a
      sample of potential students due to the many constraints put on managers, mainly
      in relation to maintaining staff morale and providing a service while staff are
      away on courses. CONCLUSION: Few studies into the effects of education on nursing
      practice adopt a randomised control trial (RCT) methodology. Most continue to be
      process rather than outcome oriented, focusing on such things as teaching and
      learning strategies. This might be related to the methodological challenges posed
      by the RCT when applied in social settings.

PMID- 11971306
TI  - Promoting women's health.
AB  - Helping women attain the best possible health means using initiatives which take
      into account the practicalities of women's lives. Health promotion activities to
      achieve this goal will need careful planning and appropriate preparation by
      nurses.

PMID- 11971308
TI  - Management of peripheral intravenous therapy.
AB  - Practice profiles are reflective pieces written by nurses in practice and based
      on continuing professional development articles. This week Frances Murray
      discusses peripheral intravenous therapy.

PMID- 11971309
TI  - Prescribing the right standards.

PMID- 11971310
TI  - The role of the nurse practitioner.

PMID- 11971313
TI  - Autonomy and the nurse practitioner.

PMID- 11971314
TI  - Grades of aspiration.

PMID- 11971317
TI  - Making a come-back.

PMID- 11971323
TI  - Back on track.

PMID- 11971324
TI  - Homing instinct. Interview by Charlotte Alderman.

PMID- 11971325
TI  - Silent minority.

PMID- 11971326
TI  - Calling in a new bank manager.

PMID- 11971327
TI  - Going up in smoke.

PMID- 11971328
TI  - Break for freedom.

PMID- 11971329
TI  - Dreaming spires--not here.

PMID- 11971330
TI  - Bouncing back. Interview by Lynn Wallis.

PMID- 11971331
TI  - Time machine.

PMID- 11971333
TI  - Professional facilitation.

PMID- 11971334
TI  - Patients' perceptions of bedside handover.
AB  - Gone are the days when a nurse would discuss a patient's progress in a matter of
      fact way behind their back when handing over their care to a colleague. Handover
      has now moved from the office to the bedside to maximise patient involvement and
      continuity of care. Catherine Greaves reveals how patients perceive this
      practice.

PMID- 11971335
TI  - A language for nursing: furthering the debate.
AB  - Continuing the debate on language for nursing, Paul Crawford and Brian Brown
      argue that merely having a common sense understanding of language is inadequate.

PMID- 11971336
TI  - Diabetic foot ulcers.
AB  - Nurses caring for people with diabetes can have an impact on the assessment and
      treatment of diabetic foot problems. This article describes a simple staging
      system to help in this important work.

PMID- 11971338
TI  - Care of the patient with dementia.

PMID- 11971340
TI  - The Tissue Viability Society.

PMID- 11971341
TI  - The management of leg ulcers in a patient with B cell cutaneous lymphoma.
AB  - Some patients suffer the consequences of skin ulceration more severely than
      others. Patients with B cell cutaneously lymphoma are one such group and this
      article reviews their special needs.

PMID- 11971343
TI  - Complacency could lead to surge in HIV infection.

PMID- 11971342
TI  - Pressure ulcers--prevention and treatment guidelines.
AB  - Nurses deal with pressure ulcers on a regular basis, yet much of the research has
      yet to be put into practice. Lyn Phillips examines the implications of the
      European Pressure Ulcer Advisory Panel's new guidelines, dealing with prevention
      and treatment of pressure ulcers.

PMID- 11971344
TI  - The implementation of clinical practice guidelines for venous leg ulcers.
AB  - Since publishing its guidelines on the management of venous leg ulcers last year,
      the RCN has worked steadily to implement and audit both the guidelines, and their
      impact.

PMID- 11971345
TI  - Abuse alert.

PMID- 11971346
TI  - Questions of confidence.

PMID- 11971349
TI  - Good grief.

PMID- 11971350
TI  - Broken promises.

PMID- 11971351
TI  - Health by stealth. Interview by Charlotte Alderman.

PMID- 11971352
TI  - Return to Romania.

PMID- 11971353
TI  - Southern crossover.

PMID- 11971354
TI  - Support act.

PMID- 11971355
TI  - Read my lips.

PMID- 11971356
TI  - A seventies solution.

PMID- 11971357
TI  - Genetic advances are your business.

PMID- 11971358
TI  - Immune system.

PMID- 11971359
TI  - Critical decisions.

PMID- 11971360
TI  - SOR points.

PMID- 11971363
TI  - Accreditation.

PMID- 11971364
TI  - Telephone contacts with a cancer nurse specialist.
AB  - AIM: The objective of this study was to audit the nature of telephone
      consultations with a Macmillan nurse specialist. METHOD: All calls made to or by
      a Macmillan nurse over a period of 20 days were analysed in respect of three main
      areas: symptom management, psychological support and treatment. Information was
      recorded on a data sheet and then data were collected and descriptive statistics
      were produced. RESULTS: The mean length of call was eight minutes. Most calls
      were incoming and involved patients, followed by relatives and healthcare
      professionals. The majority of calls involved psychological support, followed by
      symptom management then treatment. CONCLUSION: The data show that the Macmillan
      nurse specialist spends a large amount of time in telephone work, mainly in
      consultation with patients.

PMID- 11971365
TI  - Appointing a continence consultant nurse.
AB  - This article describes the process of appointing a consultant nurse for the
      promotion of continence and management and treatment of incontinence in Cornwall
      Healthcare NHS Trust.

PMID- 11971366
TI  - Defining the boundaries: nursing and personal care.
AB  - In response to the government's NHS Plan, the authors assess the difference
      between 'personal' and 'nursing' care, and outline the RCN assessment process to
      enable high quality care.

PMID- 11971367
TI  - Abdominal aortic aneurysm repair.
AB  - Rupture of an abdominal aortic aneurysm (AAA) is often a catastrophic event,
      while elective traditional repair involves major surgery. This article explains
      AAA development and traditional repair, and introduces a new, less invasive
      method of repair: endovascular stenting.

PMID- 11971375
TI  - Celebrating diversity.

PMID- 11971376
TI  - The transformer. Interview by Daniel Allen.

PMID- 11971377
TI  - Behind the signs.

PMID- 11971378
TI  - Taking a lead.

PMID- 11971379
TI  - Smash the stereotypes.

PMID- 11971380
TI  - Teething troubles.

PMID- 11971381
TI  - Plotting a course.

PMID- 11971382
TI  - In the face of violence.

PMID- 11971385
TI  - The effects of Snoezelen on chronic pain.

PMID- 11971386
TI  - Clinical guidelines in community hospitals.
AB  - AIM: The objective of this study was to investigate the attitudes of community
      hospital staff towards clinical guidelines. METHOD: Twenty four staff members
      from 11 hospitals in one community trust were interviewed. The participants,
      primarily F and G grade nurses, but also some physiotherapists and occupational
      therapists, were asked about their use of, attitudes to and sources of clinical
      guidelines. RESULTS: A simple gap analysis identified that participants were
      familiar with local clinical guidelines and generally felt positively about them,
      but had a few reservations. However, they were generally unaware of national
      guidelines. CONCLUSION: This study has identified the reality of implementing and
      raising awareness of clinical guidelines in practice.

PMID- 11971388
TI  - Using a grid framework to aid constructive thinking.
AB  - A transitional route to the recording of specialist practice for community nurses
      was undertaken via portfolio development. A grid system was developed to give a
      concise framework to follow.

PMID- 11971389
TI  - Implementing clinical education for phlebotomists.
AB  - Change is a regular occurrence in the healthcare system, but individuals might
      see it as difficult, stressful and frustrating. Implementing change with
      strategic planning and support for staff is an effective method. This article
      describes the change process for introducing a formal education programme for
      phlebotomy staff in an acute paediatric and maternity NHS trust hospital.

PMID- 11971390
TI  - Graphs: looking at relationships.
AB  - Research articles often incorporate data in the form of graphs. This article acts
      as a study guide to enable readers to understand and interpret the data produced
      in this way.

PMID- 11971401
TI  - Too close for comfort. Healthcare staff are more likely to be stalked than any
      other professional group.

PMID- 11971402
TI  - A private affair. Partnership could mean a fivefold increase in operations for
      NHS patients in private hospitals.

PMID- 11971403
TI  - Nursing her patients' dreams. Interview by Charlotte Alderman.

PMID- 11971404
TI  - Home study.

PMID- 11971405
TI  - Counting the cost.

PMID- 11971406
TI  - Wounded healers.

PMID- 11971407
TI  - Accused of misconduct.

PMID- 11971409
TI  - Ready for action.

PMID- 11971408
TI  - I'm listening....

PMID- 11971410
TI  - Out of control.

PMID- 11971411
TI  - Praying for good health.

PMID- 11971413
TI  - Conducting research involving palliative patients.
AB  - AIM: The objective of this study was to outline some of the reasons why
      palliative care patients are seen to be vulnerable as research participants.
      METHOD: The author conducted a literature review to ascertain whether or not
      palliative care patients should be involved in research. RESULTS: The author
      found that the case for involving patients who are receiving palliative care in
      research is overwhelming, but that the protection of these patients must be an
      integral part of the research. CONCLUSION: The research design should essentially
      incorporate the same aims as the palliative care philosophy: patient autonomy,
      open awareness, holism, respect and collaboration.

PMID- 11971414
TI  - Nurse-initiated thrombolysis in coronary care.
AB  - National service frameworks emphasise the importance of people who are
      experiencing a myocardial infarction receiving thrombolysis as quickly as
      possible. Nurse-initiated thrombolysis is one way to safely achieve the
      standards.

PMID- 11971415
TI  - Nutritional screening and older adults.
AB  - Nutrition is rarely included in the screening programmes of older people.
      However, nutritional screening of this population is important to distinguish
      between deterioration in their health status due to the physical decline of
      ageing and that due to nutritional deficiency.

PMID- 11971416
TI  - Food and mood.
AB  - A number of specific nutrients and other active substances in foods are thought
      to have a direct impact on mood. Carol Ottley explores the evidence linking food
      with aspects of mood and behaviour. Areas covered include premenstrual syndrome,
      chocolate craving, mood swings, and how we eat in relation to specific mood
      states such as fear, happiness and anxiety.

PMID- 11971418
TI  - Lowering the barriers.

PMID- 11971419
TI  - In the supportive role.

PMID- 11971424
TI  - Profit and loss. Private companies running NHS hospitals--dangerous experiment or
      the perfect solution?

PMID- 11971425
TI  - Your hospital needs you.

PMID- 11971426
TI  - The forgotten epidemic.

PMID- 11971427
TI  - Needle work.

PMID- 11971428
TI  - Helping the fight against HIV.

PMID- 11971429
TI  - A right performance.

PMID- 11971430
TI  - Let's hear it for the boys.

PMID- 11971431
TI  - 'The value of care given by a registered nurse will continue to be one of our
      most important campaign messages'.

PMID- 11971432
TI  - Dealing with panic.

PMID- 11971433
TI  - Encourage the quitters.

PMID- 11971434
TI  - Please don't use the term counselling so loosely.

PMID- 11971435
TI  - The right way to approach a tender subject.

PMID- 11971436
TI  - Internet access: the impact on nurses and PAMs.
AB  - An outline of a research project into the use of the internet on hospital wards
      and its impact on nurses and professionals allied to medicine.

PMID- 11971437
TI  - The lived experience of breast cancer-related lymphoedema.
AB  - AIM: This study focused on the impact that breast cancer-related lymphoedema has
      had on the lives of 20 women, who were already being treated for lymphoedema.
      METHOD: It was a qualitative research study that used data gathered from tape
      recordings of four focus groups. The data were subsequently analysed using the
      grounded theory process. RESULTS: The findings suggested that the main themes
      were finding information, suffering silently and counting blessings. CONCLUSION:
      The core category illuminated the main theme: 'Finding out information for women
      with breast cancer-related lymphoedema can help to ease their sense of anxiety
      and loss, and increase their ability to adapt to a changed life.'

PMID- 11971438
TI  - Establishing a smoking cessation support service.
AB  - Smoking cessation clinics are developing across the UK, prompted by a new drive
      to establish an evidence-based service for smokers who want to quit. Described
      here is the launch of a smoking cessation service for cardiac rehabilitation
      patients in an Oxfordshire hospital. The development of a smoking support group
      and the role of the nurse practitioner as facilitator are also described.

PMID- 11971439
TI  - Community mental health nurses, primary care and the National Service Framework
      for Mental Health.
AB  - The National Service Framework for Mental Health focuses on the mental health
      needs of adults up to the age of 65. Susan Plummer and Richard Gray discuss
      standard two by focusing on depression.

PMID- 11971440
TI  - Government offers five options for prescribing.

PMID- 11971441
TI  - Flu vaccine in short supply.

PMID- 11971442
TI  - Trust makes changes after death of newborn.

PMID- 11971443
TI  - Sink estate project will be used as a national model.

PMID- 11971444
TI  - Nursing and care home staff to join fuel protests.

PMID- 11971445
TI  - All work and no pay.

PMID- 11971446
TI  - Finishing touch.

PMID- 11971447
TI  - Against all the odds. Interview by Nick Lipley.

PMID- 11971448
TI  - On the presidential trail.

PMID- 11971449
TI  - The art of good management.

PMID- 11971450
TI  - A hidden priority.

PMID- 11971451
TI  - Look for the healer inside yourself.

PMID- 11971452
TI  - Knowledge online.

PMID- 11971453
TI  - The nurse lecturer's role in mentoring the mentors.
AB  - AIM: This article reports on the results of a survey conducted early in 1999
      investigating the effectiveness of current arrangements for mentor preparation
      and ongoing mentor support provided within adult placement areas within Greater
      Glasgow Health Board. METHOD: A sample of 150 mentors was surveyed with a
      response rate of 47 per cent (n = 71). RESULTS: Results indicate that although
      mentors are generally satisfied with the current approach to mentorship
      preparation, the issue of support from both managers and academic staff is
      problematic. CONCLUSION: Respondents indicated that they wished to see lecturers
      visiting the practice placement areas and providing support, particularly in
      relation to assessment of students. Also highlighted in this study is the need
      for more effective communication between placement areas and academic staff.

PMID- 11971454
TI  - Developing nursing research in a contract-driven arena: inequities and
      iniquities.
AB  - Despite the need for nursing to become more evidence-based, there are a number of
      problems regarding developing nursing research.

PMID- 11971455
TI  - Hand decontamination.
AB  - Hand decontamination is an important intervention in controlling hospital
      acquired infections. Dinah Gould examines the issues relating to this, including
      different decontaminants, the evidence base, the need for improvements in
      practice, and effective practice.

PMID- 11971456
TI  - Plain speaking.

PMID- 11971458
TI  - Reach for the stars.

PMID- 11971457
TI  - High flyers.

PMID- 11971459
TI  - Banking on a more flexible approach.

PMID- 11971460
TI  - A winning formula.

PMID- 11971461
TI  - Rising star. Interview by Charlotte Alderman.

PMID- 11971462
TI  - Under siege. An outbreak of the Ebola virus in Uganda has already taken its toll
      on nurses.

PMID- 11971463
TI  - Everyday heroes.

PMID- 11971464
TI  - Spirited discussion.

PMID- 11971465
TI  - Checking children for nits is parent's responsibility.

PMID- 11971466
TI  - Meningococcal C conjugate vaccines: UK campaign.
AB  - An overview of the campaign to eradicate group C meningococcal meningitis.

PMID- 11971467
TI  - Information-giving practice: an audit of patients attending a GUM clinic.
AB  - AIM: Patients are known to have difficulty assimilating information about
      diagnosis and treatment given verbally during consultations with healthcare
      professionals. Written information in the form of leaflets is often used to
      reinforce the message. The aim of this study was to audit the written and verbal
      information given to patients. METHOD: Questionnaires were given to patients
      attending the clinic for repeat treatments for genital warts. RESULTS: Female
      patients generally seemed more satisfied with the information they received than
      male patients. Overall, patients were more satisfied with verbal information than
      written information. CONCLUSION: Recommendations for changes to information
      giving practice are described and plans for future audits to help improve the
      quality and content of information are outlined.

PMID- 11971469
TI  - Rising costs could help pay claim.

PMID- 11971468
TI  - Desperate trusts pay three times more for agency staff.

PMID- 11971470
TI  - Setting up a collaborative care plan.
AB  - This article describes the creation of a collaborative care plan in a paediatric
      day surgery unit. The process of developing and using this document encourages
      collaborative care delivery and improves relationships between healthcare
      workers.

PMID- 11971471
TI  - Challenging scientific advances in mental health.
AB  - Biological and biotechnological advances in the treatment of mental health
      problems have not, according to the author, produced the benefits for patients
      that their advocates predicted. In this article, Liam Clarke argues that such
      advances are only likely to prove effective so far in the future to be irrelevant
      for clients now and in the next several generations.

PMID- 11971472
TI  - The development of diabetic ketoacidosis.
AB  - To provide nurses with a greater understanding of the condition, Helen Hand
      describes the underlying processes responsible for the development of diabetic
      ketoacidosis and discusses the need for health promotion.

PMID- 11971473
TI  - Nurses need proof of job and ID to skip fuel queues.

PMID- 11971475
TI  - Trust makes changes after death of newborn.

PMID- 11971474
TI  - Report shows sharp rise in complaints against nurses.

PMID- 11971476
TI  - Walk right in.

PMID- 11971477
TI  - Further boost for NHS Direct.

PMID- 11971478
TI  - Working party will tackle long-term care guidelines.

PMID- 11971479
TI  - A step in the right direction.

PMID- 11971480
TI  - Internet to help nurses brush up on clinical skills.

PMID- 11971481
TI  - Void left by national boards set to be filled.

PMID- 11971482
TI  - Bitterest pill?

PMID- 11971483
TI  - A lousy problem.

PMID- 11971484
TI  - The poor man's Nightingale.

PMID- 11971485
TI  - Take sanctuary.

PMID- 11971486
TI  - Nursing brain drain.

PMID- 11971491
TI  - Consumer involvement in research.

PMID- 11971492
TI  - Spirometry for patients prescribed topical beta-blockers.
AB  - AIM: To evaluate the effects of four glaucoma medications on the cardio
      respiratory system. METHOD: All newly diagnosed glaucoma (primary open-angle
      glaucoma--POAG--or normal tension glaucoma) patients were recruited into a 12
      month prospective audit. RESULTS: The study has resulted in glaucoma patients
      having a spirometry lung function test before being prescribed beta-blocker eye
      drops. The results of this study demonstrate a high level of both systemic and
      ocular side-effects caused by these topical glaucoma medications. CONCLUSION:
      This study confirms the findings of previous studies, which have shown topical
      beta-blockers to be harmful to older people with glaucoma and 'hidden' reversible
      airways disease. It also shows the consequences of using topical beta-blockers on
      patients who have previously undiagnosed respiratory and cardiac disease.

PMID- 11971494
TI  - From reforms to modernisation.
AB  - This article investigates how the 1991 and 1993 reforms have affected service
      delivery. It uses district nursing as a case study to demonstrate how a
      profession can be changed by the implementation of national health and social
      policy.

PMID- 11971495
TI  - Colposcopy.
AB  - Colposcopy is a method of examination of the cervix using an optical magnifying
      instrument. Tracy Smith discusses the assessment process, the cervical screening
      programme, management for patients who have abnormal smears, patient counselling
      and the role of the nurse colposcopist.

PMID- 11971501
TI  - Under the microscope.

PMID- 11971502
TI  - Rewarding experience.

PMID- 11971504
TI  - Autumn fever.

PMID- 11971503
TI  - Get ready for action this winter.

PMID- 11971505
TI  - Water power. Interview by Charlotte Alderman.

PMID- 11971506
TI  - 'Designer' baby: a question of ethics.

PMID- 11971509
TI  - Support for A&E nurses caring for patients with sickle cell disease.
AB  - AIM: To investigate the supportive work carried out by a health psychologist
      working with nurses in an A&E department caring for patients with sickle cell
      disease, some of whom are known to present with difficult and challenging
      behaviour. METHOD: A sample of 21 female nurses who had all taken part in the
      support group completed questionnaires concerning perceptions of the usefulness
      of the sessions, attitude changes, degree of the perceived benefit derived,
      degree of perceived comfort in the group and views about whether the sessions
      should continue. RESULTS: Most nurses found the support group useful and, since
      attending the group, many reported more sympathetic attitudes towards sickle cell
      disease patients. The forum was observed to promote reflection in practice and
      offered a degree of social support, as well as giving the nurses more confidence
      in dealing with 'difficult' patients generally. Most nurses were happy with the
      format of the support group. CONCLUSION: The support group was found to provide
      the nurses with emotional support as well as boosting their confidence in dealing
      with this patient group. This will have an impact on the quality of patient care
      they are able to deliver.

PMID- 11971510
TI  - Management of cuts, abrasions and lacerations.
AB  - The treatment of minor wounds makes up a significant proportion of the workload
      in the A&E department. Valerie Small examines the treatment options available.

PMID- 11971511
TI  - Modern wound dressings.
AB  - With the wide array of wound dressings available today, it can be a difficult
      task to select the appropriate dressing required for a particular wound. Georgina
      Casey reviews the healing process and discusses the characteristics of different
      types of dressing.

PMID- 11971517
TI  - For richer for poorer.

PMID- 11971519
TI  - Brighton flock.

PMID- 11971518
TI  - Getting in on the Act.

PMID- 11971520
TI  - Step by step.

PMID- 11971521
TI  - Eat your heart out.

PMID- 11971522
TI  - Reforms are on target.

PMID- 11971523
TI  - Spotting diabetes.

PMID- 11971524
TI  - The right to decide.

PMID- 11971525
TI  - Profession has to fight for control of nursing care.

PMID- 11971526
TI  - It's disgraceful to deny older people personal care.

PMID- 11971527
TI  - Drug names in HIV treatment.

PMID- 11971528
TI  - The care of older people.
AB  - This ongoing study examines the use of a biographical approach to enhance patient
      centred care of older people.

PMID- 11971529
TI  - Responsive assessment of clinical competence: Part 1.
AB  - AIM: To highlight the concerns that students and practitioners might have about
      the process of assessment of their nursing practice, and to suggest an
      alternative method. METHOD: Questionnaires were given to 300 student nurses and
      155 nurse practitioners throughout a Common Foundation Programme and interviews
      were conducted with 70 students and 80 assessors from three colleges of nursing.
      RESULTS: Although students generally favoured structured assessment of their
      progress, they would like some flexibility. Students acknowledged stress caused
      by continuous assessment. Assessment of clinical competence was seen to be as
      important as academic assessment. It was felt that time should be allowed to
      discuss progress during and after practical experience. Students appreciated the
      need for continuous assessment, but favoured a change in the way assessment
      booklets were used. CONCLUSION: The author suggests a new concept of continuous
      assessment of the clinical competence of students of nursing. This new model is
      called responsive assessment, in which the assessment process focuses on the
      worth and merit of the care given by students to clients/patients, as well as set
      learning objectives.

PMID- 11971530
TI  - Patient assessment and care planning: sexuality.
AB  - In this article the author examines the purpose of discussing relationships and
      sexuality at initial patient assessment. Issues such as confidentiality, referral
      to specialist services and, most importantly, the benefit to the patient are
      discussed. The article begins with a definition of sexuality and describes a
      problem-solving approach which, with training, would enable nurses to address a
      patient's sexual and relationship difficulties knowing there is appropriate help
      available.

PMID- 11971531
TI  - Primary mental health care: whose role is it anyway?
AB  - Nursing, in common with all healthcare disciplines, has had to respond to major
      developments in the wider context of health care. Shifts in government policy,
      changing preferences for the location of health care, over-stretched resources
      and new developments in medical technologies have all had a considerable impact
      on the modes of healthcare delivery, including nursing care. In times of rapid
      change, new healthcare roles emerge, others are reconstructed and some decline,
      as happened when fever nursing became obsolete owing to improvements in health
      care and living conditions during the first half of the twentieth century (Currie
      1997). Over the past two decades, some nursing disciplines have expanded
      considerably--especially those based in the community--and specialist nursing
      roles in areas such as infection control, continence care, palliative care,
      psychotherapy, tissue viability and pain management have become commonplace. This
      article examines some of the implications of the 'new NHS' for practice nurses
      and community mental health nurses (CMHNs).

PMID- 11971532
TI  - Intermittent self-catheterisation.
AB  - Intermittent self-catheterisation is a way for patients to manage a poorly
      emptying bladder with less risk of infection than is found with long-term
      indwelling catheters. Rachel Barton discusses the principles, how to identify
      suitable candidates and complications.

PMID- 11971533
TI  - Trust 'condoned' cruel abuse of older patients.

PMID- 11971534
TI  - Nurses warned the public is losing faith in regulation.

PMID- 11971535
TI  - Alliances could offer better care.

PMID- 11971536
TI  - NICE agrees to reconsider beta-interferon proposals.

PMID- 11971537
TI  - 2000 the year of the nurse?

PMID- 11971538
TI  - Breath of fresh air.

PMID- 11971539
TI  - In a perfect world....

PMID- 11971540
TI  - Nursing a statistical hangover.

PMID- 11971541
TI  - Dealing with dementia.

PMID- 11971542
TI  - Abolition of community health councils a blow to user participation.

PMID- 11971543
TI  - Mixed messages about how best to feed baby.

PMID- 11971544
TI  - Secrets and lies live on in egg donation scheme.

PMID- 11971545
TI  - Self-management of asthma.

PMID- 11971546
TI  - An evaluation of the RCN Clinical Leadership Development Programme: Part 2.
AB  - AIM: The RCN Clinical Leadership Development Programme was set up in 1995 and
      sought to identify how clinical nurses in recognised leadership positions could
      improve the quality of patient care. METHOD: The programme was tested on four
      senior nurses and 24 ward sisters in four acute hospital trusts in England over
      an 18-month period. The primary research question was whether the intervention
      improved the clinical leadership skills of participants. A pre-test/post-test
      design incorporating action research was deployed. RESULTS: On a number of
      leadership dimensions, ward sisters' and senior nurses' performance had
      significantly improved. Five key themes emerged from the process data documenting
      the journey towards more effective clinical leadership: managing self; managing
      the team; patient-centred care; networking; and becoming more politically aware.
      There was evidence to show that patient care had also improved as measured by the
      way nursing care was organised; by patients' accounts of care they received and
      by documented improvements nurses carried out as a result of direct observation
      of care. CONCLUSION: From the results of the study, it appears that there is a
      need for more effective clinical leadership development programmes for nurses to
      achieve better patient-centred care.

PMID- 11971547
TI  - Fears that election will hit long-term care timetable.

PMID- 11971548
TI  - Homes get single room reprieve.

PMID- 11971549
TI  - Proposed extensions to nurse prescribing.
AB  - Nurse prescribing has been a bone of contention for the past decade. Now, the
      government seems willing to discuss some radical possibilities.

PMID- 11971550
TI  - Nursing in outpatient child and adolescent mental health.
AB  - This article examines the role of nurses within outpatient child and adolescent
      mental health services (CAMHS). The authors highlight employment trends towards
      generic skills-based appointments such as 'clinic workers', and asserts that
      nurses with specialist training have the skills to fulfill an important role in
      CAMHS teams but are not fully recognised for their nursing contribution.

PMID- 11971552
TI  - Hint of student maternity rights.

PMID- 11971551
TI  - Nutritional benefits of drinks.
AB  - Much is known about the importance of promoting adequate nutrition, but the fluid
      content of a patient's diet is not always as strongly emphasised. Vicki Madden
      discusses the benefits of various drinks in helping to keep patients hydrated.

PMID- 11971553
TI  - Stop being so insular, nurses told.

PMID- 11971554
TI  - First three trusts receive CHI seal of approval.

PMID- 11971555
TI  - Ministers urged to back cannabis in pain control.

PMID- 11971556
TI  - War on attrition.

PMID- 11971557
TI  - Whistling in the dark.

PMID- 11971558
TI  - The influencer.

PMID- 11971559
TI  - Get your fats straight.

PMID- 11971561
TI  - Europe in crisis.

PMID- 11971562
TI  - 'Family friendly' policies don't suit everyone.

PMID- 11971560
TI  - Abuse stops here.

PMID- 11971563
TI  - We need to make a fuss about care of older people.

PMID- 11971564
TI  - A study of suicides on the railway network.

PMID- 11971566
TI  - Spanish nurses claim they weren't consulted on deal.

PMID- 11971565
TI  - The erectile dysfunction revolution.
AB  - Erectile dysfunction affects approximately one in ten men at some point in their
      lives. Edna Astbury-Ward describes its causes and the treatments available, and
      examines the effect it can have on those who experience the condition.

PMID- 11971567
TI  - Management of patients with fungating wounds.
AB  - In the absence of much literature about fungating wounds, Mark Collier presents a
      thought-provoking case history and describes the principles underpinning the
      optimal care of patients with fungating (malignant) wounds.

PMID- 11971568
TI  - Government will pay for leadership training courses.

PMID- 11971569
TI  - The role of the clinical practice educator in tissue viability nursing.
AB  - Tissue viability nursing has expanded and developed considerably in recent years.
      Julie Trudigan discusses a unique post which combines the role of the clinical
      practice educator with that of a specialist practitioner in tissue viability.
      This role focuses on practice development, which involves supporting and
      educating staff caring for patients with tissue viability needs, the development
      of multidisciplinary policies, protocols and procedures, audit of tissue
      viability services and product evaluation. The development of tissue viability
      link nurses and educational strategies such as self-directed learning and
      continued professional development are also examined.

PMID- 11971570
TI  - NHS Direct link with social services improves access.

PMID- 11971571
TI  - Call for guidelines on hygiene.

PMID- 11971573
TI  - One in four candidates fail higher level practice test.

PMID- 11971574
TI  - More money available for research.

PMID- 11971572
TI  - The use of honey in wound management.
AB  - Honey has been used as a wound treatment for more than 2,000 years. Greater
      scientific understanding of how it works, particularly as an antibacterial agent,
      has led practitioners to reconsider the therapeutic value of honey. Once honey is
      commercially available as a regulated product in the UK, practitioners will have
      access to an effective, alternative wound treatment. Specific, sterilised honeys
      intended for wound care will provide a safe natural product to manage colonised
      or infected wounds that would otherwise remain unresponsive to treatment.

PMID- 11971575
TI  - MPs condemn plan to scrap patient watchdogs.

PMID- 11971576
TI  - Nurses join forces to tackle alcohol problems.

PMID- 11971577
TI  - Flu drug approval means more work for nurses.

PMID- 11971578
TI  - Calling all the shots.

PMID- 11971579
TI  - The food chain.

PMID- 11971580
TI  - Ringing the changes.

PMID- 11971582
TI  - He's got potential.

PMID- 11971581
TI  - Right from the start.

PMID- 11971583
TI  - Out of harm's way.

PMID- 11971584
TI  - Be a real advocate--tell those doctors to wash their hands.

PMID- 11971585
TI  - Improving quality of care in chronic skin conditions.

PMID- 11971586
TI  - An evaluation of the RCN Clinical Leadership Development Programme: Part 1.
AB  - AIM: The RCN Clinical Leadership Development Programme was set up in 1995 and
      sought to identify how clinical nurses in recognised leadership positions could
      improve the quality of patient care. METHOD: The programme was tested on four
      senior nurses and 24 ward sisters in four acute hospital trusts in England over
      an 18-month period. The primary research question was whether the intervention
      improved the clinical leadership skills of participants. A pre-test/post-test
      design incorporating action research was deployed. RESULTS: On a number of
      leadership dimensions, ward sisters' and senior nurses' performance had
      significantly improved. Five key themes emerged from the process data documenting
      the journey towards more effective clinical leadership: managing self; managing
      the team; patient-centred care; networking; and becoming more politically aware.
      There was evidence to show that patient care had also improved as measured by the
      way nursing care was organised; by patients' accounts of care they received and
      by documented improvements nurses carried out as a result of direct observation
      of care. CONCLUSION: From the results of the study, it appears that there is a
      need for more effective clinical leadership development programmes for nurses to
      achieve better patient-centred care.

PMID- 11971587
TI  - Position statement on nurse-patient ratios in critical care.
AB  - The level of nurse-to-patient staffing ratios in critical care environments is a
      controversial issue. Tracy Pilcher and Mandy Odell review the literature and
      examine some of the main factors that influence staffing levels. The British
      Association of Critical Care Nurses' (BACCN) position statement is outlined.

PMID- 11971588
TI  - Lords critical of training in complementary therapies.

PMID- 11971589
TI  - Parkinson's disease: the challenge.
AB  - Parkinson's disease is a chronic and degenerative condition. Rather than
      effecting a cure, the nurse's role in caring for those with this condition is to
      enable them to live as independent a life as possible.

PMID- 11971590
TI  - NHS is 'better prepared than ever' for winter.

PMID- 11971591
TI  - Nurse-led IVF treatment could be more efficient.

PMID- 11971592
TI  - Magistrates defend stance on patients who attack staff.

PMID- 11971593
TI  - AIDS education should target men.

PMID- 11971594
TI  - NHSE bid to cut costs of adverse clinical incidents.

PMID- 11971595
TI  - NHS Direct software test reveals patchy sections.

PMID- 11971596
TI  - Rural health care falls to nurses.

PMID- 11971597
TI  - A formative evaluation of a Web-based tutorial.
AB  - Lecturers of the Department of Nursing Science of the University of Pretoria (UP)
      were requested to participate in an informal evaluation of a software program.
      The software evaluated were developed as a tutorial by the author of this
      article. The content of the tutorial concerns the current issues of the new
      education and training dispensation in South Africa, and specifically how to
      compile unit standards to meet the requirements of the South African
      Qualifications Authority (SAQA) and the National Qualifications Framework (NQF).
      The purpose of the evaluation was to assess the quality of the software.
      Participants were provided with a questionnaire, as well as criteria for the
      evaluation of software as presented in literature and information on the Web. The
      feedback has been useful and suggestions made by the participants have been used
      to improve and add to the product.

PMID- 11971598
TI  - Caring for the caregivers--a nursing management perspective.
AB  - The aim of the study was to explore the practice of caring for the caregivers in
      selected hospitals in KwaZulu-Natal. A qualitative research approach was used to
      ensure that the complexities of caring were reflected in the study. The
      qualitative analysis of the interviews with nurse managers and nurses indicated
      that they saw caring as an important part of their management task. The
      participants in the study saw caring for nurses mainly as dealing with the
      interpersonal aspects of nurses. Caring for nurses was further described in terms
      of solving the personal problems of nurses, promoting the development and growth
      needs of nurses with the focus, mainly, on the educational needs of the
      organisation itself, the welfare needs of nurses with specific reference to their
      family needs and responsibilities, and a major emphasis on HIV/AIDS issues
      arising amongst nurses themselves.

PMID- 11971599
TI  - Problem-based case study to enhance critical thinking in student nurses.
AB  - The use of traditional teaching methods, for example the lecture method, does not
      stimulate critical thinking in student nurses. This problem can be solved by the
      utilisation of problem-based case study in the classroom/clinical setting. The
      purpose of this study is to describe guidelines for the implementation of problem
      based case study in a clinical setting among first year, comprehensive course
      students at the Northern Province College of Nursing: Sovenga campus. The
      research design of this study was qualitative, explorative, descriptive and
      contextual and was conducted in the following phases: Phase 1: The development
      and implementation of a program for problem-based case study in the clinical
      setting; Phase II: The experiences of student nurses who were exposed to problem
      based case study in the clinical setting; Phase III: The perceptions of tutors
      regarding the implementation of problem-based case study in the clinical setting
      (focus group), and; ase IV: Guidelines for the implementation of problem-based
      case study. The data from Phases I, II and III were used to formulate guidelines
      for the implementation of problem-based case study. The sample group consisted of
      all 69 first year student nurses at the Northern Province College of Nursing:
      Sovenga campus and ten tutors teaching clinical courses at the same campus. The
      Tesch (1990) approach is used for data analysis. Nine guidelines for the
      implementation of a problem-based case study approach were formulated and
      recommendations for development of an instrument to measure critical thinking in
      nursing were recommended.

PMID- 11971601
TI  - Nursing care of the patient undergoing alcohol detoxification.
AB  - Nurses are challenged with the task of holistic care for the alcohol dependent
      patient. The objective of the study was to explore and describe the opinions of
      male patients regarding the holistic care in a selected detoxification unit in
      Gauteng. A quantitative, explorative and descriptive design was employed
      utilizing interviews with a structured questionnaire as method of data
      collection. After the data was analysed (frequencies were used) the results were
      presented according to the five client variables of the Neuman Systems Model.
      Positive and negative results on the physiological, psychological, socio
      cultural, developmental and spiritual needs of the client were identified. This
      article aims at identifying crucial holistic aspects of nursing care of the
      alcohol dependent patient.

PMID- 11971602
TI  - "Why me and not my neighbour?" HIV/AIDS care and counselling in a traditional
      African context.
AB  - HIV/AIDS in Africa places a tremendous burden on the nursing profession.
      Hospitals are inundated with very sick and dying AIDS patients and nurses often
      find that their role as healers has shifted to a great extent to that of
      caregivers, counsellors and educators. AIDS also calls for nurses to go beyond
      the strict Western-based bio-medical model to be able to help and understand
      patients who come from a traditional African background. This article discusses
      relevant aspects of the traditional African worldview by explaining what health,
      sickness and sexuality mean in traditional Africa. Traditional African
      perceptions of the causes of illness (God, ancestors, witches, pollution and
      germs), perceptions of sexuality, the importance of having children, cultural
      beliefs inhibiting the usage of condoms, the importance of community life, as
      well as the controversial issue of confidentiality in Africa are discussed. The
      implications for AIDS care and counselling in Africa are explored and suggestions
      on how to use traditional beliefs and customs to the advantage of AIDS education,
      are offered.

PMID- 11971603
TI  - The attitude of community health nurses towards integration of traditional
      healers in primary health care in north-west province.
AB  - South Africa is called "the rainbow nation" because it has so many different
      cultures. These have an impact on the provision of primary health care. The
      purpose of this research is to foster good relationships between community health
      nurses and traditional healers and to explore, identify and describe the attitude
      of community health nurses towards the integration of traditional healers into
      primary health care. A non-experimental, explorative and descriptive research
      strategy was designed to explore the working relationship between community
      health nurses and traditional healers. Data was collected using a structured
      questionnaire. Quantitative as well as qualitative data analysis techniques were
      adopted to interpret the findings. The results indicated that respondents
      demonstrated positive attitudes towards working with traditional healers,
      especially in the provision of primary health care. Positive opinions, ideas and
      views were provided about the integration of traditional healers into primary
      health care. Respect, recognition and sensitivity were emphasized by respondents.

PMID- 11971604
TI  - The experience of HIV reactive patients in rural Malawi--Part I.
AB  - Malawi has a population of 9 million people with AIDS the leading cause of death
      in the 20-40 age group. The HIV positive prevalence rate, estimated at 23% in
      urban areas and 8% in rural areas, is one of the highest in the world (AIDSEC,
      1994:1). Evaluation of counselling practices showed poor results with counsellors
      feeling ineffective and inadequate. Patients are mostly tested on medical
      indication but patients who do not see the benefit of knowing their HIV status
      increasingly refuse testing. The counselling practise as it is known in the
      Western world is a foreign concept for patients living in rural Malawi. The high
      stigma of AIDS complicates support of the patients. The goal of the research
      study was to describe a model of counselling that would meet the needs of an AIDS
      patient in rural community in Malawi. A qualitative research design that was
      explorative, descriptive and contextually specific to rural Malawi was used for
      the study. In order to describe a counselling model it was important to
      understand the illness experience of HIV reactive patients. The patients are seen
      in group context congruent with the African culture and therefore the experience
      of the primary care giver of AIDS patients is explored as the other major factor
      in the phenomenon examined. One phase of the research is described in this
      article namely exploring and describing the experience of the HIV reactive
      patient in rural Malawi. Results show that patients are in an advanced stage of
      AIDS when they are diagnosed and complain of weakness and an inability to do
      work, including an inability to do their daily chores. This causes a feeling of
      desperateness that is worsened by the perception that support systems are
      inadequate. Support systems are mostly identified as parents, partners and
      siblings to assist mainly with the physical care and financial support. Despite
      the fact that the family is very important to patients there is a reluctance to
      acknowledge their HIV status. Patients fear being rejected once it is known that
      they have AIDS--not only because AIDS is a sexually transmitted disease, but also
      because it is perceived that financial and other support will be withheld if it
      is known that patients have AIDS and will therefore die and not be able to return
      the support provided. Patients feel they have no future once a diagnosis of AIDS
      has been made which results in refusal of testing, as they do not see the benefit
      of knowing their HIV status. Assessing the coping ability of the patient within
      the household as part of an overall assessment is one proposed strategy that
      could be taken. Secondly the patient is encouraged to take a more active role in
      the counselling process, which could be achieved by narration. The family should
      be incorporated into the counselling process as early as possible.

PMID- 11971605
TI  - A care counselling model for HIV reactive patients in rural Malawi--Part II.
AB  - The purpose of the research conducted was to explore and describe HIV patients
      experience of their illness within the context of rural Malawi and, based on the
      results of the study, to describe a model for counselling HIV reactive patients
      in rural Malawi which would meet both the internal and external needs of the
      patient. Nursing for the Whole Person Theory, as well as symbolic interactionism
      and the research model of Botes, were used as paradigm, as the researcher
      believes a person is fundamentally a historical social being who can only be
      understood in a specific cultural context of space and time. The research was
      also conducted within a counselling context and different disciplines were
      integrated in the study. The research method followed two phases each addressing
      a different objective. Firstly, exploration and description of the HIV reactive
      individual's experience of illness, compilation of a demographic profile of the
      patients in the study and a description of their identified needs as well as
      possible resources, exploration and description of the primary care givers'
      experience of HIV reactive patients and the exploration and description of the
      viewpoint of counsellors in terms of counselling HIV reactive patients. In the
      first phase of the study in-depth phenomenological interviews were conducted with
      identified groups. Focus interviews were conducted with a hundred AIDS patients
      to identify the needs and resources of the patients and to compile a demographic
      profile. Focus groups discussions were conducted with counsellors for more
      complete comprehension. Data-analysis and literature control was undertaken. In
      the second phase of the study theory generation was used in order to develop a
      counselling model for AIDS patients and guidelines for implementing the model
      were generated. Based on the results of the analysis the major concept enable was
      identified as the essence of a model for counselling AIDS patients in rural
      Malawi. The visual model developed described a process of enablement with the
      counsellor as negotiator and the patient as a narrator in which the patient,
      family and community are encouraged to participate actively. By utilising the
      deductive reasoning strategy, relationship statements were inferred from the
      model. Guidelines were described for all three phases of the model, namely
      pretest counselling, post-test counselling and community care, in terms of
      objectives, strategies and activities. The value of this research was embodied in
      addressing a very real and urgent need in Malawi and proposing a solution with
      practical guidelines.

PMID- 11971606
TI  - Evaluation of the Integrated Community-Based Home Care model.
AB  - In 1999-2000 the Integrated Community-Based Home Care model for the care of
      people with AIDS in communities were implemented in seven sites across the
      country. The post-implementation evaluation showed that most respondents felt
      that the model could be replicated if a functioning and informed network
      including all partners, and a strong management team were in place. The effects
      of the project were mainly positive for all stakeholders (hospice, clinic,
      hospital, PWA and their carers, professionals and other community members).
      Hospitals and community-based services became more aware of and involved in the
      needs of PWA and felt that the model enabled them to address these needs. PWA and
      their carers felt supported and respected.

PMID- 11971607
TI  - The knowledge and practices of primary care givers regarding home-based care of
      HIV/AIDS children in Blantyre (Malawi).
AB  - Knowledge is one of the major factors that promotes adherence to treatment
      regimens. With the current trends worldwide of home and community-based services
      for the management of HIV/AIDS patients, knowledge of care givers about the home
      care of these patients will determine the success of the programs. The purpose of
      this descriptive study was to explore the knowledge and practices of primary care
      givers of HIV/AIDS children in the provision of home care services. In this study
      an attempt was made to describe the factors which are associated with knowledge.
      Thirty-six primary care givers were randomly selected from three major home based
      care centres in Blantyre City, Malawi. A structured interview schedule was used
      to collect data. Data were analysed manually and by computer, using the
      Statistical Package for Social Science (SPSS). The findings revealed a gap in
      knowledge since in many instances taking a child to the hospital for the
      management of minor ailments was the action of choice, thus perpetuating the
      problem of overburdening hospital resources. Lack of prior preparation for home
      based care was found to be the major factor contributing to the lack of
      knowledge. Recommendations proposed include the need to put into place mechanisms
      that will ensure that all the primary care givers are adequately prepared in good
      time for home care service. Ensuring regular home visits was also thought to be
      helpful for efficient and effective supervision and reinforcement of information
      given to fill the gaps in knowledge wherever necessary.

PMID- 11971609
TI  - Nothing but the truth.

PMID- 11971610
TI  - Nurses as clinicians, teachers and researchers.

PMID- 11971608
TI  - Touching lives, creating opportunities, seeking challenges.

PMID- 11971611
TI  - Bavarian nursing secrets revealed.

PMID- 11971612
TI  - The Irsee vision: healing patients by healing practitioners.

PMID- 11971613
TI  - From Helsinki to Terre Haute.

PMID- 11971614
TI  - Teaching and learning in Indonesia.

PMID- 11971615
TI  - Mission of nursing.

PMID- 11971616
TI  - Life's experiences haven't hurt me none.

PMID- 11971617
TI  - My evolving self: from dean to faculty member (with apologies to Robert Kegan).

PMID- 11971618
TI  - Asylum seekers: let's do the right thing.

PMID- 11971619
TI  - Pressure sores on increase, study says.

PMID- 11971624
TI  - A care model for faecal incontinence management in the community.

PMID- 11971625
TI  - Mandatory detention: protection or punishment?

PMID- 11971626
TI  - Easier to keep quiet in a culture of silence.

PMID- 11971627
TI  - Examining the phases of nursing care of the hospitalised child.

PMID- 11971629
TI  - Insurance premium rises 'a bit rich': PM.

PMID- 11971628
TI  - Supporting child and adolescent nursing developments.

PMID- 11971630
TI  - Bioterrorism. Can we meet the healthcare challenge?

PMID- 11971631
TI  - Disaster preparedness 2002.

PMID- 11971632
TI  - Queuing or sharing? A critical evaluation of the single-bottleneck notion.
AB  - The model of a single central bottleneck for human information processing is
      critically examined. Most evidence cited in support of the model has been
      observed within the overlapping tasks paradigm. It is shown here that most
      findings obtained within that paradigm and that were used to support the model
      are also consistent with a simple resource model. The most prominent findings are
      the millisecond-for-millisecond slope at the left of the RT2-SOA curve, the high
      RT1-RT2 correlation, the additivity of the effects on RT2 of SOA and of the
      difficulty of selecting R2, and the washout of the effect of S2 discriminability
      on RT2 in a dual-task condition. In addition, the asymmetry of the effects of the
      dual-task requirement on RT1 and RT2 can be accounted for by the resource model
      provided that it assumes uneven allocation of resources, which is quite
      reasonable in view of the task asymmetry inherent in the demand characteristics
      of the paradigm. The same is true for two other findings that appear to support
      the single-bottleneck model-that in the dual-task condition, the demand of the
      first task affects equally RT1 and RT2 and that its effect on RT1 is the same as
      the corresponding effect in the single-task condition. Furthermore, the single
      bottleneck model is hard to reconcile with a negative slope at the left of the
      RT1-SOA curve or a positive slope at the left of the IRI-SOA curve, unless
      augmented by ancillary assumptions that are yet to be substantiated.
      Representative data were fit by each of the models using its optimal set of
      parameters. Both models achieved quite good degrees of fit. It is further argued
      that since the overlapping tasks paradigm is heavily biased in favor of a speedy
      reaction to the stimulus that appears first, it is nonoptimal for testing the
      central bottleneck model. Finally, the bottleneck model is examined in terms of
      other scientific criteria.

PMID- 11971633
TI  - Arrows of time in infancy: the representation of temporal-causal invariances.
AB  - Many transformations that take place over time can only occur in one temporal
      direction, and adults are highly sensitive to the differences between forward and
      backward presentations of such events. In seven experiments using two selective
      looking paradigms, 4- and 8-month-olds were shown forward and backward videotapes
      of events involving the effects of gravity on liquids and solid objects and of
      the separation of whole objects into pieces. Four-month-olds showed a significant
      preference for the forward version of liquid pouring from a beaker to a glass.
      Eight-month-olds looked longer at the forward versions of this and four other
      gravity-related events but showed no directional preferences for the separation
      events. Several experiments indicate that longer looking at the forward versions
      of the gravity stimuli is not a product of attraction to specific perceptual
      features of the stimuli. A model based on the development of representations of
      types of events is presented and evaluated.

PMID- 11971634
TI  - Task switching: a PDP model.
AB  - When subjects switch between a pair of stimulus-response tasks, reaction time is
      slower on trial N if a different task was performed on trial N - 1. We present a
      parallel distributed processing (PDP) model that simulates this effect when
      subjects switch between word reading and color naming in response to Stroop
      stimuli. Reaction time on "switch trials" can be slowed by an extended response
      selection process which results from (a) persisting, inappropriate states of
      activation and inhibition of task-controlling representations; and (b)
      associative learning, which allows stimuli to evoke tasks sets with which they
      have recently been associated (as proposed by Allport & Wylie, 2000). The model
      provides a good fit to a large body of empirical data, including findings which
      have been seen as problematic for this explanation of switch costs, and shows
      similar behavior when the parameters are set to random values, supporting Allport
      and Wylie's proposal.

PMID- 11971635
TI  - Sublethal effects of pentachlorophenol in abalone (Haliotis rufescens) veliger
      larvae as measured by (31)P-NMR.
AB  - Toxicity tests with larval marine organisms are widely used as water quality
      monitoring tools. Often employing a single morphological endpoint, they provide
      only limited insight into toxic action mechanisms. Since mechanistic observations
      can provide more sensitive endpoints of toxicity, the goal of this study was to
      modify existing in vivo (31)P-NMR techniques to evaluate the effects of
      pentachlorophenol (PCP) on high-energy phosphates in veliger larvae of the red
      abalone (Haliotis rufescens), a species and life stage commonly used in
      developmental toxicity tests. Fluxes of phosphoarginine (PA), nucleoside
      triphosphates (NTPs), sugar phosphates (SPs), and inorganic phosphate (P(i)), as
      well as in intracellular pH (pH(i)), were monitored via NMR using a flow-through
      exposure system. The exposure protocol included 1 h of clean seawater, 2 h of PCP
      (1.2 mg L(-1)) exposure, and 2 h of recovery in clean seawater. During PCP
      exposure, veligers displayed maximum declines in PA and NTP resonance intensities
      to 38+/-10% (P<0.01) and 61+/-16% (P<0.05) of reference values (represented by
      the average resonance intensities taken from 1 h of preexposure spectral
      acquisition). Inorganic phosphate concentrations rose to 302+/-63% (P<0.01), and
      pH(i) declined from a reference period average of 7.12+/-0.03 to 7.04+/-0.04
      (P<0.05). On exposure to clean seawater, veligers recovered within 2 h, returning
      to 196+/-53, 89+/-12, and 89+/-13% of the reference intensities for P(i), PA, and
      NTPs, respectively (P>0.05 for all values), while pH(i) increased to 7.08+/-0.11.
      When compared with adult abalone, veliger larvae responded similarly to PCP,
      differing mainly in their rapid recovery (2 h for larvae versus 6 h adults) and
      more severe acidification (a 0.08 pH unit decline versus a 0.03 pH unit decline).
      This report describes an application of NMR for small (> or =200 micro) marine
      organisms using commonly available vertical-bore NMR magnets; it should prove
      adaptable for use with other similar larval forms.

PMID- 11971636
TI  - Evaluation of tributyltin subchronic effects in tropical freshwater fish
      (Astyanax bimaculatus, Linnaeus, 1758).
AB  - Tributyltin (TBT) is widely used as a biocide in antifouling paints. Astyanax
      bimaculatus adult fish were acclimatized in a laboratory and isolated in groups
      of eight individuals. Two groups were used as a control (similar handling and
      corn oil control) and one group was exposed to TBTCI dissolved in corn oil
      (0.0688 +/- 0.0031 microg TBT.g(-1)) every 6 days for 32 days. Light and
      transmission electron microscopy were used to investigate the morphological
      effects on liver. A muscle fragment was excised for the determination of the
      acetylcholinesterase activity and blood smears were obtained for differential
      white cell counts. The results indicated nuclear irregular shapes, chromatin
      condensation, presence of intranuclear lipid bodies, and degenerative nuclei.
      Acetylcholinesterase activity was not affected by TBT exposure. The increasing
      number of neutrophils may represent cytotoxic and stress conditions facilitating
      the invasion of opportunist organisms. According to the authors' data, TBT was
      confirmed as a powerful aquatic contaminant to fish in tropical ecosystem.

PMID- 11971637
TI  - Sex differences in hepatic lipids of Toxaphene-exposed juvenile yellowtail
      flounder (Pleuronectes ferrugineus Storer).
AB  - Histochemical and biochemical effects of Toxaphene on liver were investigated in
      laboratory-bred female and male juvenile yellowtail flounder (Pleuronectes
      ferrugineus). Fish were fed uncontaminated food, or food contaminated with hexane
      (the solvent for Toxaphene) or with one of two concentrations of Toxaphene (0.02
      or 0.2 microg/g fish/day) for 2 weeks. Males were more advanced in sexual
      maturity than females, although all were from the same year-class (0(+)). Liver
      tissue examined histochemically (Sudan black B, oil red O) revealed that
      Toxaphene affected storage of total and neutral lipids according to sex and dose.
      The sexes differed in the amount of total and neutral lipids. Neutral lipid
      droplets were considerably larger in the liver of females. Lipids were extracted
      and analyzed using the latroscan TLC/FID system. Triacylglycerols comprised the
      majority of lipids. Animals exposed to the lowest concentration of Toxaphene
      stored low amounts of total and neutral lipids and high amounts of polar lipids,
      while animals exposed to a 10 times higher concentration showed the reverse.
      Sterols were highest in animals exposed to the highest dose. Thus Toxaphene can
      alter the lipid composition in the liver of yellowtail flounder, which may have
      consequences for physiological processes involving the liver, such as lipid
      metabolism and reproduction.

PMID- 11971638
TI  - Effect of insecticides on plankton and fish of Ignacio Ramirez reservoir
      (Mexico): a biochemical and biomagnification study.
AB  - Studies on the limnology, plankton, and biomagnification of pesticides at Ignacio
      Ramirez (IR) reservoir (Mexico) were undertaken. The reservoir is located in
      central Mexico, in an agricultural zone with high soil erosion.
      Acetylcholinesterase (AchE), gamma-glutamyl transpeptidase (GGTP), and lipid
      peroxidation were assayed in fish. Organochlorines (0.024-0.279 mg/liter) and
      organophosphates (0.02 x 10(-3)-0.21 x 10(-3) mg/liter) were present at high
      concentrations in water and the biota assayed. In the IR dam the plankton
      fluctuated depending on the dry and wet seasons. The dominant group of
      phytoplankton was Bacillariophyta (20-85%) in May, Cyanophyta (22-65%) in
      September, and Cyanophycean (10-65%), Chlorophycean (10-60%), and
      Bacyllariophycean (5-80%) species in March. The zooplankton were dominated by
      cladoceran species (40-70%). Organochlorine and organophosphate insecticides were
      bioconcentrated (2- to 10-fold) from water to algae, 10- to 25-fold in
      zooplankton, and 8- to 140-fold in fish. GGTP activity and lipid peroxidation
      increased and AchE activity in fish decreased in response to the environmental
      stress caused by the elevated biomagnification of pesticides. The bioaccumulation
      of these contaminants in fish and the potential for biomagnification in humans
      are perceived as threats.

PMID- 11971639
TI  - Decline in reproductive success, sex reversal, and developmental alterations in
      Japanese medaka (Oryzias latipes) after continuous exposure to octylphenol.
AB  - Japanese medaka (Oryzias latipes) were continuously exposed to concentrations of
      0, 2, 20, and 50 microg/L octylphenol, 0.01 per thousand dimethyl sulfoxide, and
      100 ng/L 17beta-estradiol from 2 to 4 h postfertilization until maturity.
      Exposure to > or =2 microg/L octylphenol caused a 20-30% increase in mortality
      both before and after hatch. Growth was significantly decreased in fish exposed
      to 50 microg/L octylphenol and in the positive control. Sex ratio changed from
      42:58 (females:males) in controls to 57:40 at 50 microg/L octylphenol, and 3 and
      4% of the medaka exposed to 50 microg/L octylphenol and 17beta-estradiol
      developed testes-ova. In cross-mating experiments, mating of exposed males with
      control females resulted in an up to 11% lower fertilization rate than in
      controls. Results indicate that continuous exposure to octylphenol causes a broad
      variety of reproductive effects, which can be correlated with the xenoestrogenic
      potential of octylphenol.

PMID- 11971640
TI  - Observations on metal concentrations in tilapia (Oreochromis mossambicus) in
      reservoirs of south Sri Lanka.
AB  - Samples of the muscle and liver of tilapia (Oreochromis mossambicus) obtained
      from the five reservoirs in four catchments in southern Sri Lanka in 1998 were
      analyzed for 16 elements: As, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Sr,
      and Zn by inductively coupled plasma emission spectrophotometry, and Hg by atomic
      absorption spectrophotometry. The concentrations of Cr, Ni, and Pb were below the
      detection limits of the instrumental techniques employed in all samples. The
      elements As, Ca, Co, Cu, Fe, Hg, K, Mg, Mn, Na, Sr, and Zn were detected in the
      muscle and liver tissue, with Cd detected in some liver samples. There were no
      statistically significant differences between the individual concentrations of
      any of the metals and the site from which the tilapia were collected (P>0.05).
      Furthermore, no statistically significant correlations were found between total
      length of fish and metal concentration. No elements were found at concentrations
      of toxicological concern. However, a principal component analysis suggests that
      the populations of tilapia in the reservoirs may be exposed to different regimes
      of metals, possibly associated with different catchment land-use patterns.

PMID- 11971641
TI  - Ecotoxicity of chromium (III) to Eisenia fetida, Enchytraeus albidus, and
      Folsomia candida.
AB  - Despite growing concerns about the potential adverse effects of elevated chromium
      concentrations in the environment, only a few terrestrial toxicity data are
      available. Therefore, chronic toxicity of chromium(III) was assessed for Eisenia
      fetida, Enchytraeus albidus, and Folsomia candida, the three invertebrates for
      which standard test protocols are available. The 21-day EC(50) for the cocoon
      production of E. fetida was 892 (679-1110) mg Cr/kg dry weight. Based on the
      reproduction, a 42-days EC(50) of 637 (355-791) mg Cr/kg dry weight was observed
      for E. albidus, while for F. candida a 28-day EC(50) of 604 (254-3380) mg Cr/kg
      dry weight was noted. Although the presented data can be considered a step
      forward in the assessment of the potential risks of chromium(III) in terrestrial
      environments, further research is needed to evaluate the influence of soil
      parameters on the toxicity of chromium and to quantify the effect of aging on
      bioavailability.

PMID- 11971642
TI  - Optical algal biosensor using alkaline phosphatase for determination of heavy
      metals.
AB  - A biosensor is constructed to detect heavy metals from inhibition of alkaline
      phosphatase (AP) present on the external membrane of Chlorella vulgaris
      microalgae. The microalgal cells are immobilized on removable membranes placed in
      front of the tip of an optical fiber bundle inside a homemade microcell. C.
      vulgaris was cultivated in the laboratory and its alkaline phosphatase activity
      is strongly inhibited in the presence of heavy metals. This property has been
      used for the determination of those toxic compounds.

PMID- 11971644
TI  - Combined effects of algal (Chlorella vulgaris) density and ammonia concentration
      on the population dynamics of Ceriodaphnia dubia and Moina macrocopa (Cladocera).
AB  - Ammonia is a natural variable in ponds and lakes. Although an important source of
      nitrogen for microalgae, at high concentrations ammonia can affect the density
      and diversity of cladocerans. Using the cladocerans Ceriodaphnia dubia, and Moina
      macrocopa, the effect of nominal concentrations of ammonium chloride under acute
      and chronic exposures at different levels of algal food was tested. Regardless of
      food level, C. dubia was more sensitive than M. macrocopa to ammonia. In the
      absence of food, the median lethal concentration of ammonia (LC(50) 24 h) for C.
      dubia was (112 mg L(-1)) less than half that of M. macrocopa (232 mg L(-1)). When
      algal food (0.5 x 10(6) and 1.5 x 10(6) cells ml(-1) of Chlorella) was used, the
      LC(50) values were much higher for both cladoceran species. Based on the
      population growth studies, it was found that in controls of M. macrocopa an
      increase in the availability of Chlorella from 0.5 to 1.5 x 10(6) cells mL(-1)
      led to an increase in the maximum density from 4.7 +/- 0.2 to 16.4 +/- 1.2
      ind.mL(-1), while in C. dubia the peak population density decreased from 7.9 +/-
      0.6 to 5.0 +/- l.0 ind.mL(-1). An increase in ammonia concentration (10 to 40 mg
      L(-1) for C. dubia and 20 to 120 mg L(-1) for M. macrocopa) resulted in a
      corresponding decrease in peak population densities of the tested cladocerans.
      The rate of population increase (r) values for M. macrocopa in the controls
      ranged from 0.21 +/- 0.001 and 0.25 +/- 0.02 at 0.5 and 1.5 x 10(6) cells mL(-1)
      of Chlorella, respectively. The corresponding values of C. dubia in controls were
      0.21 +/- 0.004 and 0.18 +/- 0.01. At 0.5 x 10(6) cells mL(-1) of algal food, the
      r values became negative under 40 and 120 mg L(-1) of ammonia for C. dubia and M.
      macrocopa, respectively. The role of algal food in ammonia toxicity to
      cladocerans was discussed. (c) 2002 Elsevier Science (USA).

PMID- 11971643
TI  - Lack of modifying effects of 4-n-octylphenol on 3,2'-dimethyl-4-aminobiphenyl
      induced prostate carcinogenesis in rats.
AB  - The modifying effects of dietary feeding of an estrogenic compound 4-n
      octylphenol on 3,2'-dimethyl-4-aminobiphenyl (DMAB) induced prostatic
      carcinogenesis were investigated in male F344 rats. The authors also assessed the
      effects of test compound on proliferating cell nuclear antigen (PCNA) index in
      induced neoplasms, hyperplastic lesions, and nonlesional glands in the prostrate.
      Rats were given intraperitoneal injections of DMAB (25 mg/kg body wt) every other
      week, 10 times, to induce prostatic neoplasms. They also received the
      experimental diet containing 10 or 100 ppm 4-n-octylphenol for 20 weeks, starting
      one week after the last dosing of DMAB. DMAB exposure produced prostatic
      adenocarcinoma with an incidence of 21% at the end of the study (Week 39).
      Dietary administration of 4-n-octylphenol did not affect the incidence of
      prostatic adenocarcinoma: 17% in DMAB-->10 ppm 4-n-octylphenol group; and 12% in
      DMAB-->100 ppm 4-n-octylphenol group. The PCNA indices in adenocarcinomas,
      hyperplastic lesions, and nonlesional glands in rats treated with DMAB and 4-n
      octylphenol were slightly lower than that of the DMAB alone group, but the
      differences were not statistically significant. These results might suggest that
      dietary feeding of the weak estrogenic compound 4-n-octylphenol did not have
      modulating effects on DMAB-induced rat prostatic carcinogenesis.

PMID- 11971645
TI  - Morpho-histochemical changes in the gills of turbot, Scophthalmus maximus L.,
      induced by sodium dodecyl sulfate.
AB  - The present article reports the effect on survival as well as morpho
      histochemical changes in the gills of juvenile turbot Scophthalmus maximus L.,
      induced by acute action of the anionic surfactant sodium dodecyl sulfate (SDS).
      First, LC(50) at 96 h was found to be 7.5 mg/L of SDS. Second, lots with 20
      individuals were exposed to SDS concentrations of 3, 5, 7, and 10 mg/L in order
      to obtain the exposure time required for 50% mortality of the specimens (384,
      190, 12, and 4 h) and surface tension values (60.2, 56, 54.9, and 53.3 mN/m),
      respectively. Finally, histopathological lesions (clubbing and fusion of the
      secondary lamellae, hyperplasia and posterior rupture of the respiratory
      epithelium, destruction and shortening of gill filaments, and the presence of
      hemorrhagic foci) and histochemical alterations in the distribution of
      carbohydrates and proteins in the gills of treated specimens were noted. These
      morpho-histochemical changes in the gills provoked functional disorders (i.e.
      asphyxia and the loss of osmotic and ionic regulation) that may ultimately play
      an important role in the mortality of turbots exposed to SDS.

PMID- 11971647
TI  - Base compositional bias in trans-spliced sequences of unknown function in
      Leishmania major.

PMID- 11971648
TI  - Trypanosoma congolense: expression of a heat shock protein 70 and initial
      evaluation as a diagnostic antigen for bovine trypanosomosis.
AB  - A 69-kDa immunodominant protein of Trypanosoma congolense was identified as a
      member of the hsp70 family that is homologous to mammalian BiP. We report here
      the expression of the gene encoding the T. congolense BiP in a bacterial system.
      Dot blotting of the truncated recombinant proteins confirmed that BiP
      antigenicity is mainly located in the C-terminal third of the molecule. A
      recombinant fragment corresponding to this region was used as an antigen in an
      indirect ELISA and an initial evaluation of its diagnostic potential for bovine
      trypanosomosis was performed. The test showed limited sensitivity for detection
      of primary-infected cattle but was capable of accurately detecting secondary
      infections. As BiP and its derivatives may be produced at low cost under stable
      forms allowing standardization of the tests, they warrant further evaluation as
      antigens fro serodiagnosis of bovine trypanosomosis.

PMID- 11971650
TI  - Development of symbionts in triatomine bugs and the effects of infections with
      trypanosomatids.
AB  - In the intestinal tract of fifth instars of the hematophagous reduviid bugs
      Rhodnius prolixus and Triatoma infestans blood ingestion induced an initial
      decrease of the concentration of the respective symbiotic bacteria Rhodococcus
      rhodnii and Nocardia sp. and then within 10 days a 15- or 18-fold increase of the
      total population/bug to about 0.8 x 10(9) colony-forming units in R. prolixus and
      1.8 x 10(9) colony-forming units in T. infestans. About 95-99% of the total
      populations of both symbionts developed in the anterior midgut regions, i.e.,
      cardia and stomach. The passage from the blood-storing stomach to the digesting
      small intestine caused a considerable breakdown of symbiont populations, and only
      about 0.01% of the total population was present in the rectum. These were
      excreted mainly within 4 h after a blood meal. After infection with three species
      of trypanosomatids, R. rhodnii, the symbiont of R. prolixus, was affected by
      Trypanosoma rangeli, but not by Blastocrithidia triatomae or Trypanosoma cruzi.
      On the other hand, in T. infestans the concentration of Nocardia sp. was reduced
      after infection with B. triatomae, but not by T. rangeli nor T. cruzi. In long
      term B. triatomae-infected T. infestans, this reduction and a reduced diuretic
      activity after feeding synergistically lowered the symbiont concentration in the
      singly deposited feces/urine drops drastically compared to uninfected controls.
      These data strongly support the theory of the mechanisms of pathogenicity of T.
      rangeli and B. triatomae for R. prolixus and T. infestans, respectively, that the
      primal point of attack is the host-specific symbiont, R. rhodnii and Nocardia
      sp., respectively.

PMID- 11971649
TI  - Plasmodium yoelii sporozoites infect CD36-deficient mice.

PMID- 11971652
TI  - Fluorescent vital labeling to track cestodes in a copepod intermediate host.
AB  - In experimental studies of host-parasite interactions, it is often important to
      track parasites in their hosts and to discriminate between individual parasites.
      We used the fluorescent tracer dyes 7-amino-4-chloromethylcoumarin (CMAC) and, 5
      chloromethylfluorescein diacetate (CMFDA) for vital labeling of Schistocephalus
      solidus (Cestoda) coracidia larvae. Labeling was fast and easy to perform and
      enabled microscopic detection of parasites appearing as procercoids in the
      hemocoel of the copepod intermediate host at 3 h after exposure. The label was
      still visible after 14 days. Extensive controls showed that CMAC (20 microM)
      labeling did not harm tapeworms or copepods. CMFDA (2 microM) reduced host
      survival, but the dye concentration can be decreased to avoid this in future
      studies. The new labeling method presented here has been very useful to track S.
      solidus parasites. It can be valuable for other parasites also and may be
      particularly suitable for visualization of individual live macroparasites in
      invertebrate hosts, for which we are not aware of any other appropriate method.

PMID- 11971651
TI  - Plasmodium falciparum: in vitro interactions of artemisinin with amodiaquine,
      pyronaridine, and chloroquine.
AB  - In the scenario of drug-resistant Plasmodium falciparum malaria combination
      therapy represents an effective approach. Artemisinin and its derivatives are of
      special interest because they represent the most effective group of compounds
      against multidrug-resistant malaria with a rapid onset of action and a short half
      life. Interactions of artemisinin with amodiaquine, pyronaridine, and chloroquine
      were therefore investigated against three strains of P. falciparum using a 48-h
      in vitro culture assay. Two of the strains were chloroquine sensitive and one was
      partially chloroquine resistant. Observed effective concentrations (O) of the
      combined compounds at different concentration ratios were calculated for
      different degrees of inhibition (EC50, EC90, EC99) and compared to expected
      calculated effective concentrations (E) using a probit method. Synergism with
      mean O/E EC90 values of 0.25 and 0.8 were found with the combination of
      artemisinin and the two Mannich bases, amodiaquine and pyronaridine,
      respectively, whereas chloroquine showed addition with a mean value of 1.2.
      Although both amodiaquine and chloroquine are 4-aminoquinolines, their
      interaction with artemisinin appears to be different. The combination of
      artemisinin with amodiaquine represents an important option for the treatment of
      falciparum malaria.

PMID- 11971653
TI  - Leishmania mexicana: identification of genes that are preferentially expressed in
      amastigotes.
AB  - The protozoan parasite Leishmania has a digenetic life cycle, alternating between
      the promastigote and the amastigote stages. Amastigotes infect macrophage cells
      and reside in the hydrolytic environment of the phagolysosome. Leishmania show
      distinct morphological and biochemical changes during differentiation into
      amastigotes. These alterations are believed to be regulated by stage-specific
      expression of a discrete number of genes. Selective-suppression PCR, a PCR-based
      subtractive hybridization technique, identified two genes preferentially
      expressed in L. mexicana lesion amastigotes: a novel gene family, A600, and a
      differentially expressed beta-tubulin gene. Northern blot analysis confirmed
      amastigote-specific expression of these genes and quantitation showed a sixfold
      higher abundance of A600 and beta-tubulin transcripts in lesion amastigotes. The
      A600 gene was predicted to contain a 293-bp open reading frame (ORF) that was
      tandemly repeated in the L. mexicana genome. Sequence analysis predicted that the
      A600 ORF encodes either a membrane-bound or a secreted protein that may have a
      functional role in amastigote differentiation or intraphagolysosomal parasite
      survival.

PMID- 11971654
TI  - Mitochondrial NADH dehydrogenase from Plasmodium falciparum and Plasmodium
      berghei.
AB  - The mitochondrial electron transport system is necessary for growth and survival
      of malarial parasites in mammalian host cells. NADH dehydrogenase of respiratory
      complex I was demonstrated in isolated mitochondrial organelles of the human
      parasite Plasmodium falciparum and the mouse parasite Plasmodium berghei by using
      the specific inhibitor rotenone on oxygen consumption and enzyme activity. It was
      partially purified by two sequential steps of fast protein liquid chromatographic
      techniques from n-octyl glucoside solubilization of the isolated mitochondria of
      both parasites. In addition, physical and kinetic properties of the malarial
      enzymes were compared to the host mouse liver mitochondrial respiratory complex I
      either as intact or as partially purified forms. The malarial enzyme required
      both NADH and ubiquinone for maximal catalysis. Furthermore, rotenone and
      plumbagin (ubiquinone analog) showed strong inhibitory effect against the
      purified malarial enzymes and had antimalarial activity against in vitro growth
      of P. falciparum. Some unique properties suggest that the enzyme could be
      exploited as chemotherapeutic target for drug development, and it may have
      physiological significance in the mitochondrial metabolism of the parasite.

PMID- 11971655
TI  - Toxoplasma gondii partially inhibits nitric oxide production of activated murine
      macrophages.
AB  - Activated macrophages produce nitric oxide (NO) and as such are able to control
      the multiplication of Toxoplasma gondii. Until now, no reports have described a
      possible modulation of NO production of macrophages after T. gondii infection. To
      investigate this possibility, murine blood monocyte-derived and peritoneal
      macrophages were activated in vitro with interferon-gamma and lipopolysaccharide
      and infected with T. gondii and Trypanosoma cruzi, and NO production was
      evaluated. NO was produced by monocyte-derived macrophages only if cultured in
      the presence of macrophage-colony-stimulating factor. Monocyte-derived or
      peritoneal macrophages infected with T. gondii presented a significant reduction
      in NO production. NO production inhibition was not detected after T. cruzi
      infection. Macrophages infected with higher T. gondii/macrophage ratios presented
      lower NO production. Furthermore, only viable T. gondii could cause partial
      inhibition of NO production. In macrophages activated 24 h before the
      interaction, partial inhibition was detected after 3 h of infection and continued
      for 48 h. In macrophages activated immediately after the interaction, partial
      inhibition was not detected at 12 h, but was observed at 24 h. T. gondii-infected
      macrophages present lower inducible nitric oxide synthase expression as assayed
      by immunofluorescence. T. gondii did not develop in monocyte-derived macrophages
      producing NO, but were not totally eliminated. These results demonstrate that T.
      gondii infection partially inhibits NO production by murine macrophages,
      suggesting that a deactivating macrophage mechanism may be used for better
      survival into phagocytic cells.

PMID- 11971656
TI  - Leishmania infantum (Protozoa, kinetoplastida): transmission from infected
      patients to experimental animal under conditions that simulate needle-sharing.

PMID- 11971657
TI  - Effects of insect hormones on hemagglutination activity in two members of the
      Culex pipiens complex.
AB  - Effects of methoprene and 20-hydroxyecdysone on the development and
      hemagglutination activity (HA) were studied in both sexes of two members of the
      Culex pipiens complex-anautogenous C. p. quinquefasciatus and autogenous C. p.
      molestus. Juvenile hormone analogue (methoprene) and 20-hydroxyecdysone caused
      developmental changes in both mosquito strains. High larval mortality,
      prolongation of intermolt period in each larval instar and in the pupal stage,
      and morphological changes in the larval-pupal and pupal-adult transformations
      were also observed. Developmental changes were accompanied with some differences
      in the HA. HA was found in both sexes of both experimental mosquito strains. The
      juvenile hormone analogue used in the larval stage caused significant decrease of
      HA in the gut of adults of both sexes. On the other hand, 20-hydroxyecdysone
      decreased HA only in the female gut. Results obtained indicate that HA depends on
      the sex, the studied organ, and the level of hormones.

PMID- 11971658
TI  - Oral testosterone self-administration in male hamsters: dose-response, voluntary
      exercise, and individual differences.
AB  - Although testosterone was declared a controlled substance in 1990, the potential
      for steroid dependence is largely unexplored. The present study used food-induced
      drinking with oral testosterone self-administration in hamsters to determine (1)
      the dose-response for testosterone reward, (2) links between testosterone self
      administration and voluntary exercise, and (3) factors predicting individual
      differences in androgen intake. Testosterone (1-4 mg/ml) was presented in aqueous
      solution 3 h/day for 35 days, with and without food. At 3 mg/ml, testosterone
      maintained fluid intake, even without food (3.0 +/- 0.2 ml/3h). At 4 mg/ml, fluid
      intake declined to 2.4 +/- 0.3 ml/3h in the presence of food. However, no dose
      response relationship between testosterone self-administration and reward was
      observed. To test the interaction of testosterone and exercise, males drinking
      testosterone (RUN + T) or vehicle received a running wheel. Additional males self
      administered testosterone without exercise. Testosterone intake correlated
      positively with exercise and negatively with body weight in RUN + T males.
      Experiment 3 determined the relationship between testosterone self-administration
      and mating or saccharin preference. There were no statistically significant
      correlations. However, testosterone self-administration increased mating
      behavior. These data demonstrate that testosterone is a mild reinforcer. Although
      preference for androgens is not predicted by mating or saccharin intake,
      testosterone intake is linked with voluntary exercise.

PMID- 11971659
TI  - Endogenous estradiol and testosterone levels are associated with cognitive
      performance in older women and men.
AB  - Relatively few studies have investigated the relationship between endogenous sex
      steroid levels and cognition in older people and the reported results have been
      inconsistent. A number of experimental hormone replacement studies have suggested
      that estrogen replacement in older women enhances cognition, especially verbal
      memory. In contrast, little research has been done focusing on men. In the
      current study the association between endogenous sex steroids (estradiol and
      testosterone) and cognition was investigated in 38 healthy older women (mean age
      68 years) and 30 healthy older men (mean age 69 years). Five cognitive tests
      measuring verbal memory, spatial memory, verbal fluency, mental rotation, and
      susceptibility to interference were administered. Results revealed that in women
      higher estradiol levels as well as testosterone levels were associated with
      better verbal memory (paired associates and estradiol; r =.38, P < 0.05; paired
      associates and testosterone; r =.33, P < 0.05;). Moreover estradiol, but not
      testosterone was associated with less susceptibility to interference (Stroop
      color word test; r = -0.34, P < 0.05). In men the only significant association
      was a negative correlation between testosterone and verbal fluency (r = -0.38, P
      < 0.05). The associations observed in this small study support the notion that
      estradiol is protecting verbal memory and possibly also frontal lobe mediated
      functions in older women. In contrast to the positive findings in women
      endogenous sex steroids do not appear to be closely linked to better cognition in
      older men.

PMID- 11971661
TI  - Individual and seasonal variation in fecal testosterone and cortisol levels of
      wild male tufted capuchin monkeys, Cebus apella nigritus.
AB  - This study tested the "challenge hypothesis" and rank-based predictions for
      temporal steroid production in male tufted capuchin monkeys, Cebus apella. Fecal
      samples (n = 209) collected from six wild males were analyzed for testosterone
      and cortisol concentration by enzyme immunoassay. The temporal pattern in male
      steroid production was compared to female sexual activity and rates of male
      aggression. The top-ranking adult male did not differ from other adult males in
      testosterone or cortisol concentration. Mean adult testosterone was significantly
      higher than mean subadult testosterone throughout the year. There was a clear
      elevation of testosterone and cortisol in both adult and subadult males during
      the peak of adult female sexual activity after the birth season. In fact, the
      magnitude of increase in testosterone was higher than predicted for a species
      with low male-male aggression. However, there was no difference between
      nonbreeding baseline testosterone levels during the birth season, and the
      "breeding" baseline of testosterone in males found during asynchronous female
      sexual activity. Of all behavioral indices examined, the distribution of female
      maintained consortships was the best predictor of mean adult male testosterone
      concentrations. Although in many species, elevated testosterone coincides with
      increased male-male aggression, in the present study, the sustained high
      magnitude increase in steroids during the peak of adult female sexual activity
      was associated with a relatively low rate of male-male intragroup aggression.

PMID- 11971660
TI  - Effects of angiotensin II microinjected into medial amygdala on male sexual
      behavior in rats.
AB  - Research was undertaken to study the role of central angiotensin in the
      modulation of male sexual behavior, testing the effect of angiotensin II (Ang II)
      injections into the medial amygdaloid nucleus (MeA). The sexual behavior of adult
      male Wistar rats was evaluated, 15 min after bilateral intra-amygdaloid
      microinjection (0.3 microl) of saline and 5 doses of Ang II: 10; 25; 50; 100, and
      150 fmol. The effects of the Ang II receptor blockade were also studied. We
      tested the effect of coinjection of Ang II (50 fmol) with the AT1 antagonist,
      losartan (20 pmol) and the AT2 antagonist, CGP 42112 (1 pmol). Ang II inhibited
      sexual behavior and this inhibition was prevented by the coinjection of AT1
      antagonist, losartan, or the AT2 antagonist, CGP 42112. Results show that Ang II
      has a powerful effect on male sexual behavior, which may be mediated by both AT1
      and AT2 receptors.

PMID- 11971662
TI  - Genotype/age interactions on aggressive behavior in gonadally intact estrogen
      receptor beta knockout (betaERKO) male mice.
AB  - Estrogen, as an aromatized metabolite of testosterone, has a facilitatory effect
      on male aggressive behavior in mice. Two subtypes of estrogen receptors, alpha
      (ER-alpha) and beta (ER-beta), in the brain are known to bind estrogen. Previous
      studies revealed that the lack of ER-alpha gene severely reduced the induction of
      male aggressive behavior. In contrast, mice that lacked the ER-beta gene tended
      to be more aggressive than wild type (WT) control mice, although the behavioral
      effects of ER-beta gene disruption were dependent on their social experience.
      These findings lead us to hypothesize that estrogen may facilitate aggression via
      ER-alpha whereas it may inhibit aggression via ER-beta. In the present study, we
      further investigated the role of ER-beta in the regulation of aggressive behavior
      by examining developmental changes starting at the time of first onset, around
      the age of puberty. Aggressive behaviors of ER-beta gene knockout (betaERKO) mice
      were examined in three different age groups, puberty, young-adult, and adult.
      Each mouse was tested every other day for three times in a resident-intruder
      paradigm against olfactory bulbectomized intruder mice and their trunk blood was
      collected for measurements of serum testosterone after the completion of the
      study. Overall, betaERKO mice were significantly more aggressive than WT. These
      genotype differences were more pronounced in puberty and young adult age groups,
      but not apparent in the adult age group, in which betaERKO mice were less
      aggressive than those in two younger age groups. Serum testosterone levels of
      betaERKO mice were significantly higher than those of WT mice only in the
      pubertal age group, but not in young adult (when betaERKO mice were still
      significantly more aggressive than WT mice) and adult (when no genotype
      differences in aggression were found) age groups. These results suggest that ER
      beta mediated actions of gonadal steroids may more profoundly be involved in the
      inhibitory regulation of aggressive behavior in pubertal and young adult mice.

PMID- 11971663
TI  - Exposure to estradiol before but not during acquisition of LiCl-induced
      conditioned taste avoidance accelerates extinction.
AB  - Estradiol accelerates extinction of LiCl-induced conditioned taste avoidance when
      it is present continuously before and during acquisition. We have suggested that
      the effect of estradiol on extinction is due to its illness-associated, rather
      than learning-associated, properties. If this were the case, then one would
      expect estradiol to act before but not during acquisition. This expectation is
      based on previous work showing attenuation of learned taste avoidance when rats
      are given distal preexposure (greater than 24 h before conditioning) or proximal
      preexposure (less than 24 h before conditioning) to the illness-inducing agent
      LiCl before acquisition of a LiCl-induced conditioned taste avoidance. In three
      separate experiments, estradiol was administered during three different time
      periods via subcutaneous implantation of a 10-mm estradiol-filled capsule. In
      each experiment, the extinction of estradiol-treated females was compared to that
      of females implanted with empty capsules. In the first experiment, female rats
      were given distal exposure to estradiol before acquisition. Capsules were
      implanted 11 days before acquisition and were removed 2 days before acquisition.
      In the second experiment, female rats were given proximal exposure to estradiol
      before acquisition. Capsules were implanted 2.5 h before LiCl was paired with a
      sucrose solution and were removed 16.5 h later. In the third experiment, female
      rats were given exposure to estradiol during acquisition. Capsules were implanted
      at the same time as LiCl administration and were removed 18 h later. The only
      estradiol-treated females to show accelerated extinction were those given distal
      preexposure to estradiol in Experiment 1. These data do not support a learning
      associated hypothesis and only partially support an illness-associated
      hypothesis. The failure to find accelerated extinction following proximal
      preexposure may reflect an inappropriate choice of the parameters used in the
      experiment or a difference in the stimulus properties of LiCl and estradiol that
      allow each to serve as conditioning and preexposure agents in conditioned taste
      avoidance paradigms [corrected].

PMID- 11971664
TI  - Changes in progesterone metabolites in the hippocampus can modulate open field
      and forced swim test behavior of proestrous rats.
AB  - The purpose of these experiments was to test the hypothesis that attenuating the
      endogenous increase of the 5alpha-reduced progesterone metabolite 5alpha-pregnan
      3alpha-ol-20-one (3alpha,5alpha-THP) in the hippocampus will alter anxiety and
      depression behavior of proestrous rats. In Experiment 1, anxiety (open field) and
      depression (forced swim test) behavior was compared of rats that should have high
      (proestrous) and low (diestrous and male rats) endogenous hippocampal
      3alpha,5alpha-THP. Proestrous rats exhibited more anxiolytic-like (increased
      central entries in the open field) and anti-depressant-like (less immobility in
      the forced swim test) behavior than diestrous or male rats. In Experiments 2 and
      3, respectively, systemic and intrahippocampal finasteride, a 5alpha-reductase
      inhibitor which attenuates progesterone's metabolism to 3alpha,5alpha-THP, versus
      vehicle administration to proestrous rats was compared for effects on open field
      and forced swim test behavior. Systemic or intrahippocampal finasteride decreased
      central entries in the open field and increased immobility in the forced swim
      tests compared to vehicle administration. In Experiment 4, the effects of
      systemic and intrahippocampal finasteride vs vehicle administration on
      hippocampal 3alpha,5alpha-THP of proestrous rats was examined. Finasteride, SC or
      intrahippocampally, reduced 3alpha,5alpha-THP in the hippocampus compared to
      vehicle administration. Together these data suggest that variations in
      3alpha,5alpha-THP levels in the hippocampus may mitigate proestrous changes in
      anxiety and depressive behavior of cycling rats.

PMID- 11971665
TI  - Food deprivation inhibits estrous behavior in hormone-treated Syrian hamsters
      despite elevated estradiol levels.
AB  - Estradiol and progesterone (P) induce female mammalian reproductive behaviors,
      which are, in turn, sensitive to food availability. When ovariectomized, steroid
      primed hamsters are food deprived for 48 h, estrous behavior is suppressed. While
      this suppression of estrous behavior may be due to alterations in neural steroid
      receptor levels, it is also possible that decreased levels of circulating
      estradiol could be involved in mediating this suppression. Ovariectomized Syrian
      hamsters given varying doses of estradiol benzoate (EB) and P were tested to
      determine whether increasing doses of sex steroids would overcome the suppressive
      effects of food deprivation on estrous behavior. As expected, lordosis duration
      decreased in food-deprived animals. Increasing the levels of EB, but not P,
      increased lordosis duration in the food-deprived animals so that animals who were
      given 20 microg of EB had lordosis durations significantly longer than food
      deprived hamsters that received 1.5 microg and 2.5 microg EB. Following an
      injection of 2.5 microg of EB, food-deprived hamsters actually had higher
      circulating levels of estradiol than ad libitum-fed animals. Therefore,
      increasing circulating levels of estradiol can increase lordosis durations in
      fasted animals; however, the suppression of estrous behavior occurs despite
      increased circulating estradiol levels in ovariectomized, steroid-treated
      animals. The most parsimonious explanation for this phenomenon is a deprivation
      induced reduction in neural responsiveness to estradiol.

PMID- 11971666
TI  - Fraternal birth order and birth weight in probably prehomosexual feminine boys.
AB  - The purpose of this study was to confirm a previous finding that homosexual males
      with older brothers weigh less at birth than do heterosexual males with older
      brothers. The subjects comprised 250 feminine boys referred to a child psychiatry
      service because of extreme cross-gender wishes or behavior and assumed, on the
      basis of previous research, to be prehomosexual, plus 739 control boys and 261
      control girls referred to the same service for reasons unrelated to sexual
      orientation or gender identity disorder and assumed, from base-rate
      probabilities, to be preheterosexual. The feminine boys with two or more older
      brothers weighed 385 g less at birth than did the control boys with two or more
      older brothers (P = 0.005). In contrast, the feminine and control boys with fewer
      than two older brothers did not differ in birth weight. This finding suggests
      that the mechanism by which older brothers increase the odds of homosexuality in
      later-born males operates prior to the individual's birth. We hypothesize that
      this mechanism may be immunologic, that antimale antibodies produced by human
      mothers in response to immunization by male fetuses could decrease the birth
      weight of subsequent male fetuses as well as increase their odds of
      homosexuality.

PMID- 11971667
TI  - Glucose but not protein or fat load amplifies the cortisol response to
      psychosocial stress.
AB  - We previously reported that glucose intake amplifies cortisol response to
      psychosocial stress and smoking in healthy young men, while low blood glucose
      levels prevented the stress-induced activation of the hypothalamus pituitary
      adrenal (HPA) axis. However, it remains unknown whether this modulation is
      specific for glucose load or a more common effect of energy availability. To
      elucidate this question, 37 healthy men, who fasted for at least 8 h before the
      experiment, were randomly assigned to four experimental groups, who received
      glucose (n = 8), protein (n = 10), fat (n = 10), and water (n = 9), one h before
      their exposure to the Trier Social Stress Test (TSST). Blood glucose levels were
      measured at baseline and following stress, while salivary cortisol was assessed
      repeatedly measured before after the TSST. The results show that both absolute
      cortisol levels and net cortisol increase were greater in the glucose group in
      comparison to the other groups (F(3,33) = 3.00, P < 0.05 and F(3,33) = 3.08, P <
      0.05, respectively. No group differences were observed with respect to perceived
      stress and mood. Furthermore, the cortisol response was positively correlated
      with blood glucose changes (r = 0.49, P < 0.002). In conclusion, the results
      suggest a central mechanism responsible for regulation of energy balance and HPA
      axis activation, rather than peripheral mechanisms. We thus recommend controlling
      for blood glucose levels when studying HPA axis responsiveness.

PMID- 11971668
TI  - Social stimuli, testosterone, and aggression in gull chicks: support for the
      challenge hypothesis.
AB  - We tested the challenge hypothesis for the hormonal regulation of aggression in
      chicks of the black-headed gull, Larus ridibundus. Chicks of this species are
      highly aggressive toward conspecifics, but never to peers that hatched from the
      same clutch (modal clutch size is three). Therefore, in the first experiment
      small families were housed together in large groups (challenged condition) and
      compared to families kept isolated (nonchallenged condition). As expected, in the
      challenged condition during the initial stage of territory establishment basal
      levels of testosterone (T) were clearly higher than those in the nonchallenged
      condition. In the second experiment we tested the effect of a short social
      challenge on short-term T-fluctuations. The design was based on an earlier
      experiment, showing that after temporary T-treatment chicks become very sensitive
      to social challenges while having low basal T-levels. We now show that these
      social challenges induce brief elevations in plasma T-levels. These peaks are
      similar to those in previously untreated chicks but untreated chicks do not
      respond with aggression to a challenge. Therefore, we conclude that the initial
      exposure to elevated T-levels increases the sensitivity to brief changes in T
      induced by social challenges. In this way exposure to T, that may be detrimental
      for development, is minimized while birds remain able to defend territories. This
      is the first report showing that the challenge hypothesis as established for
      adult birds, is also applicable for aggressive behavior in young birds outside
      the sexual context. Furthermore we suggest that a phase of priming with T is
      necessary to obtain the high behavioral responsiveness to a challenge.

PMID- 11971670
TI  - The Association for Academic Surgery, an idea whose time has come?

PMID- 11971669
TI  - Olfactory bulb cells generated in adult male golden hamsters are specifically
      activated by exposure to estrous females.
AB  - Two experiments were carried out to test whether cells which are born in
      adulthood and migrate to the olfactory bulb of adult male golden hamsters are
      activated during sexual behaviors, to determine the time course over which such
      responsiveness appears, and to ask whether activation is specific to sexual cues.
      In the first experiment, adult male hamsters were injected with 5'
      bromodeoxyuridine (BrdU, 50mg/kg b.w.) 3 times over the course of one week in
      order to mark dividing cells. Ten days, three weeks, or seven weeks after the
      first BrdU injection, the animals were allowed to mate with an estrous female for
      half an hour before being sacrificed. Confocal analysis of fluorescent
      immunostaining of BrdU and c-Fos first revealed dual labeled cells in the
      olfactory bulb 3 weeks after injection of the thymidine analog. In order to
      determine whether the activation of these newly generated cells is specific to
      sexual cues, we next compared the incidence of c-Fos expression in newborn (BrdU
      positive) cells among male hamsters exposed to an estrous female, an aggressive
      male, a cotton swab containing vaginal secretion from an estrous female hamster
      (FHVS), a cotton swab containing peppermint, or a cotton swab containing
      distilled water. In the mitral and glomerular layers of the accessory olfactory
      bulb, animals exposed to an estrous female had significantly more double labeled
      cells than did those given other treatments (p < 0.01). In the mitral layer of
      the main bulb, animals exposed to an estrous female had a significantly higher
      percentage of double labeled cells than those of other groups, except those
      exposed to an aggressive male (p < 0.05). No double labeled cells were seen in
      medial preoptic area (MPOA), medial nucleus of the amygdala (Me), the bed nucleus
      of the stria terminalis (BNST), or the hypothalamus. Our results indicate that
      cells born in adulthood are more responsive to cues arising from estrous females
      than other stimuli, and thus may participate in sociosexual behaviors.

PMID- 11971671
TI  - Military trauma training performed in a civilian trauma center.
AB  - BACKGROUND: In 1996, Congress passed legislation requiring the Department of
      Defense to conduct trauma training in civilian hospitals. In September of 1998 an
      Army team composed of surgeons, nurses, emergency medical technicians (EMTs), and
      operating room technicians (OR techs) trained in a civilian level 1 trauma
      center. This study analyzes the quality of the training. METHODS: The training
      period was 30 days. Before and after training all members completed a
      questionnaire of their individual and team ability to perform at their home
      station, at the civilian hospital, and in the combat setting. Surgeons maintained
      an operative log, which was compared with their prior year's experience. Primary
      trauma cases (PTCs) met Residency Review Committee criteria as defined category
      cases and were done acutely. Other personnel tracked the percentage of supporting
      soldier tasks (SSTs) they performed or were exposed to during the training
      period. RESULTS: Review of the questionnaires revealed a significant increase in
      confidence levels in all areas tested (P < 0.005). The three general surgeons
      performed a total of 42 PTCs during the 28 call periods, or 1.5 PTCs per call
      period. During the prior year, the same three general surgeons performed 20 PTCs
      during 114 call periods for 0.175 cases per call period (P = 0.003). The maximum
      number of PTCs performed during one call period at the civilian center was 4,
      compared with 5 PTCs performed by one Army surgeon during the Somalia 1993 mass
      casualty event. Performance of or exposure to SSTs was 71% for the EMTs, 94% for
      the nurses, and 79% for the OR techs. CONCLUSIONS: A 1-month training experience
      at a civilian trauma center provided military general surgeons with a greater
      trauma experience than they receive in 1 year at their home station. Other
      personnel on the team benefited by performing or being exposed to their SSTs.
      Further training of military teams in civilian trauma centers should be
      investigated.

PMID- 11971673
TI  - Vascular smooth muscle cells derived from atherosclerotic human arteries exhibit
      greater adhesion, migration, and proliferation than venous cells.
AB  - BACKGROUND: Phenotypic variation of vascular smooth muscle cells (VSMC) may
      result in altered biological behavior and responses. Within the vessel wall,
      arterial VSMC have a greater propensity to form atherosclerotic lesions as
      compared to venous VSMC. In this study the rates of proliferation, adhesion, and
      migration were compared between VSMC of atherosclerotic arterial and venous
      origin. MATERIALS AND METHODS: Human VSMC cultures were isolated from 18
      infragenicular arteries at the time of below knee amputation and from 20
      saphenous veins during lower extremity revascularization surgery. Cell cultures
      were isolated from the media of each specimen and maintained in distinct cell
      lines for all assays. Cells from passages 2 and 3 were assayed for their
      proliferative capacity using total DNA fluorescence photometry and for adhesion
      and migration using a modified Boyden chamber. RESULTS: Patient age and the
      incidence of atherosclerotic risk factors did not vary significantly between the
      arterial and the venous patient groups. VSMC of atherosclerotic arterial origin
      demonstrated greater proliferation (arterial, 162 +/- 59 absorption units, vs.
      venous, 106 +/- 56 absorption units, P < 0.001), adhesion (arterial, 74.1 +/-
      22.6 cells/microscopic field, vs. venous, 41.3 +/- 12.8 cells/microscopic field,
      P < 0.001) and migration (arterial, 427 +/- 185 cells/microscopic field, vs
      venous, 119 +/- 101 cells/microscopic field, P < 0.001) than VSMC of venous
      origin. CONCLUSION: Human atherosclerotic arterial VSMC exhibit significantly
      increased rates of proliferation, adhesion, and migration as compared to human
      venous VSMC. These observations of VSMC in culture are consistent with the
      clinical predilection for the hyperplasic responses that result in the
      development of atherosclerosis in the arterial wall. Possible intrinsic
      differences in VSMC phenotype should be considered in designing methods to limit
      atherosclerosis.

PMID- 11971672
TI  - Nitric oxide inhibition increases aortic wall matrix metalloproteinase-9
      expression.
AB  - OBJECTIVE: Nitric oxide (NO) may mediate vessel wall remodeling by regulating
      expression of matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs). This study tested the hypothesis that nitric oxide
      synthase (NOS) inhibition in whole aortic wall causes increases in cytokine
      stimulated MMP and TIMP expression. METHODS: Cultured infrarenal aortic segments
      from Sprague-Dawley rats were exposed to increasing concentrations (0, 0.1, 0.5,
      1, and 5 mM; n = 6 per concentration) of N(G)-monomethyl-l-arginine (L-NMMA), a
      known inhibitor of NOS. This was in the presence of 2 ng/ml of interleukin-1beta,
      a known inducer of NOS, MMP, and TIMP expression. Media nitrate and nitrite
      (NO(x)) were measured at 72 h using the Saville method. Media MMP activity was
      measured using gelatin zymography. MMP-2 and -9 protein and mRNA levels were
      determined by Western blot and reverse transcriptase-polymerase chain reaction
      (RT-PCR). TIMP activity and mRNA levels were evaluated by reverse zymography and
      RT-PCR. Data were analyzed using ANOVA. RESULTS: Increasing concentrations of L
      NMMA produced a dose-dependent decrease in NO(x) (2214 +/- 405 to 347 +/- 37
      ng/mg, P < 0.001). Zymography demonstrated a dose-dependent increase in 92-kDa
      MMP (pro-MMP-9) activity (P < 0.001) with corresponding increases in pro-MMP-9
      protein (P = 0.03) and mRNA levels (P = 0.004). While there was a dose-dependent
      increase in 72-kDa MMP (pro-MMP-2) activity (P = 0.001), pro-MMP-2 protein and
      mRNA levels were unchanged. Reverse zymography demonstrated a dose-dependent
      increase in 29-kDa TIMP-1 activity (P = 0.01), but there was no change in TIMP-1
      mRNA levels. CONCLUSIONS: NOS inhibition in ex vivo aortic tissue causes a dose
      dependent increase in MMP-9 expression and activity. It is speculated that
      deficiencies of NO in vivo alter MMP and TIMP homeostasis, favoring matrix
      degradation.

PMID- 11971674
TI  - CD1-dependent natural killer (NK1.1(+)) T cells are required for oral and portal
      venous tolerance induction.
AB  - BACKGROUND: Local antigen presentation via either the oral (PO) or the portal
      venous (PV) routes results in suppression of systemic delayed-type
      hypersensitivity (DTH). The responsible cell populations are not well defined.
      Because NK1.1(+) T cells express the Fas ligand and produce high levels of the
      immunosuppressive cytokine, IL-4, they may play a role in both activated T-cell
      apoptosis and a Th1 to Th2 immune shift, thus promoting tolerance induction.
      METHODS: C57BL/6 mice were tolerized to BALB/c alloantigen by PV or PO spleen
      cells (25 x 10(6)) on Day 0. Subcutaneous (SQ) challenge with 10 x 10(6) BALB/c
      cells on Day 7 was followed by footpad injection of 10 x 10(6) BALB/c cells on
      Day 14. Footpad swelling was measured 24 h later. A single injection of the
      NK1.1(+) cell-depleting antibody, PK-136, was given IP (10 mg/kg) 2 days prior to
      PV or PO antigen. Flow cytometry evaluated NK1.1(+) cell depletion. CD1 knockout
      (KO) mice, lacking NK1.1(+) T cells, were also challenged with PV and PO Balb/c
      in parallel experiments. RESULTS: The DTH to BALB/c antigen was markedly
      suppressed in C57BL/6 mice when this alloantigen was given by either PO or PV
      routes (P < 0.001, P < 0.001). The maintenance of an unaltered response to third
      party C3H/HeJ demonstrated alloantigenic specificity. Administration of the anti
      NK1.1 T cell monoclonal antibody, PK-136, resulted in complete restoration of in
      vivo DTH responsiveness in PO tolerance (P < 0.01), and partial restoration in PV
      tolerance (P < 0.05) in C57BL/6 mice. FACS confirmed virtually complete depletion
      of liver, splenic, Peyer's patch, and mesenteric lymph node NK1.1(+) lymphocytes.
      Development of both PO and PV tolerance was prevented in CD1 KO mice. CONCLUSION:
      NK1.1(+) T cells play an essential role in antigen-specific suppression of the
      DTH response mediated by both oral and portal venous tolerance.

PMID- 11971675
TI  - Does the subjective evaluation of medical student surgical knowledge correlate
      with written and oral exam performance?
AB  - BACKGROUND: Medical student performance evaluations have historically contained a
      significant subjective component. Multiple tools are used to assess fund of
      knowledge including subjective evaluation by faculty and residents as well as
      objective evaluations through standardized written and oral exams. We
      hypothesized that subjective evaluation of medical student knowledge would
      correlate with objective evaluation through written and oral exams. METHODS:
      Records of consecutive medical students assigned to the surgery clerkship from
      January 1999 and March 2001 were reviewed. The core surgical rotation consisted
      of two 4-week blocks on a private, county, or VA hospital service. Surgical
      knowledge was assessed subjectively by both faculty (FES) and senior residents
      (RES) using a 10-point scale with verbal anchors. Objective measures of student
      surgical knowledge included the National Board shelf exam (WE) and a
      semistructured oral exam (OE). Data are reported as mean +/- SEM. Spearman rank
      correlation coefficient (r) was used to assess relationships between groups (r >
      or = 0.5 --> positive correlation). RESULTS: A total of 354 students were
      evaluated. The mean FES was 7.8 +/- 0.05 (median = 7.75, range 4.75 to 9.75). The
      mean RES was 7.7 +/- 0.06 (median = 8.0, range 3.5 to 10.0). There was poor
      correlation between the subjective perception and objective measures of surgical
      knowledge (Table 1). Comparison of the FES and RES also showed poor correlation
      (r = 0.38). CONCLUSIONS: Subjective evaluation of surgical knowledge by faculty
      and residents correlates poorly with performance measured objectively. These
      results question whether subjective evaluation of surgical knowledge should be
      included as part of the evaluation process.

PMID- 11971676
TI  - Intraoperative communication of residents with faculty: perception versus
      reality.
AB  - INTRODUCTION: During a surgical procedure, an attending may propose a surgical
      treatment that a resident believes is not the standard of care based on previous
      readings, discussions with other faculty, or experience. We hypothesized that
      resident disagreements over intraoperative management are common and are handled
      differently by residents than faculty members perceive. METHODS: Surveys were
      sent to 68 residents (82% response) and 45 faculty (91% response) in general
      surgery and seven subspecialties. Questions were asked to determine the frequency
      of disagreements and the differences in perceptions of how residents should act
      when they have disagreements over the intraoperative decisions of attendings.
      Significance was defined using Fisher's exact test at P < 0.05. RESULTS:
      Residents reported having major disagreements with faculty over intraoperative
      decisions as often as monthly (41%) or two to three times per year (37%).
      Estimates of the frequency of major resident disagreements did not differ between
      attendings and residents. Fewer residents felt comfortable asking the faculty to
      discuss their intraoperative decisions than was perceived by faculty members (41%
      vs 78%, P < 0.001). Residents at all levels are less comfortable than perceived
      by their mentors in discussing intraoperative decisions even when residents
      believe that patient injury may result. Residents felt that most of their
      disagreements occurred because of attending knowledge deficit, while most
      attendings attributed these differences to resident knowledge deficits.
      CONCLUSION: Residents frequently have disagreements with faculty over
      intraoperative management. Education to improve preoperative and intraoperative
      communication between surgical residents and faculty is needed.

PMID- 11971677
TI  - Induction of NF-kappaB, IkappaB-alpha, and iNOS in rat gastric mucosa during
      endotoxemia.
AB  - Upregulation of inducible nitric oxide synthase (iNOS) contributes to the
      development of gastric injury during endotoxemia. The molecular mechanisms
      related to its induction are unknown. Because the transcription factor nuclear
      factor-kappa B (NF-kappaB) regulates inflammatory genes in response to
      endotoxemia, we hypothesized that its activity in gastric mucosa would increase
      while its inhibitor IkappaB-alpha would decrease commensurate with changes in
      iNOS expression. Rats were given intraperitoneal saline or lipopolysaccharide
      (LPS; 20 mg/kg) for 5, 15, or 30 min, or for 1, 3, or 5 h, and killed, and the
      gastric mucosa was prepared for determination of iNOS and IkappaB-alpha by
      Western immunoblotting, iNOS mRNA by quantitative real-time RT-PCR, and NF-kappaB
      by electrophoretic mobility-shift assay. LPS caused a significant increase in
      iNOS mRNA and protein immunoreactivity at 1, 3, and 5 h compared to controls. NF
      kappaB-binding activity increased in the nuclear fraction of gastric mucosa at 1
      h and steadily increased over time after LPS administration. The activated NF
      kappaB consisted mainly of p50 with a lesser amount of p65 subunits as
      demonstrated by a supershift assay. IkappaB-alpha decreased in gastric cytosolic
      fractions over time, consistent with its degradation. These data suggest that
      during endotoxemia expression of the inflammatory mediator iNOS in the gastric
      mucosa may be upregulated by degradation of IkappaB-alpha and subsequent
      translocation of NF-kappaB into the nucleus and increased NF-kappaB activity.

PMID- 11971679
TI  - Posttranslational alanine trans-stimulation of zwitterionic amino acid transport
      systems in human intestinal Caco-2 cells.
AB  - BACKGROUND: Neutral dietary amino acids, such as alanine, are transported across
      the gut lumen by both Na(+)-dependent (System B) and Na(+)-independent (System L)
      carriers, but the nature of the acute phase of substrate-induced uptake is
      unknown. This study examined the effects of acute amino acid substrate exposure
      on the rapid modulation of apical membrane alanine transport in cultured human
      intestinal cells. METHODS: System B and System L transport activity kinetics, as
      well as ATB(0) mRNA levels, were measured in confluent Caco-2 monolayers treated
      with various metabolic agents during short-term and extended time periods.
      RESULTS: Depleting the incubation medium of alanine attenuated both System B and
      System L uptake activities within 30 mins, with a complete return to baseline
      values within 3 h. Extracellular alanine added to depleted Caco-2 cells rapidly
      (within 5 min) increased alanine transport activities. Kinetic analysis showed
      that acute alanine exposure increased both K(m) and V(max) of each transport
      system, indicative of a trans-stimulation effect. Augmenting intracellular
      alanine levels using the cytosolic alanine aminotransferase inhibitor,
      aminooxyacetic acid, increased alanine uptake activity. Acute exposure to other
      substrates of Systems B and L also increased the uptake of alanine, while
      nonsubstrates did not affect alanine uptake. Cycloheximide or actinomycin did not
      affect substrate acute activation of System B, and the steady-state level of
      ATB(0) mRNA was not altered by amino acid exposure. CONCLUSION: Increasing
      alanine availability to intestinal cells, by either exogenous substrate exposure
      or inhibition of intracellular catabolism, acutely and reversibly increases
      apical membrane alanine transport activity via a posttranslation trans
      stimulation mechanism.

PMID- 11971678
TI  - Induction of murine AIDS virus-related sequences after burn injury.
AB  - To better understand the molecular signaling events leading to systemic
      inflammatory response syndrome (SIRS) and multiple organ failure (MOF), changes
      in gene expression profiles after burn injury were investigated by differential
      display. C57BLKS/J mice were subjected to 18% total body surface area (TBSA) full
      thickness burn and various tissues were harvested at multiple time points after
      injury. Initial differential display revealed that retroviral transcripts similar
      to the envelope sequence of murine AIDS (MAIDS) virus were rapidly and
      transiently up-regulated after injury. Subsequent RT-PCR and DNA sequencing
      analyses confirmed the transient up-regulation of retroviral sequences similar to
      those of the MAIDS virus. In addition, the presence and induction of the
      subgenomic envelope transcripts of these MAIDS virus-related sequences, including
      a novel double spliced message, were identified after burn injury. These data
      suggest that the transcriptional efficiency of the integrated retroviral DNA and
      reactivation of defective MAIDS virus-related sequences may be affected by
      pathophysiological signals, such as burn injury. The elevated expression of these
      MAIDS virus-related retroviral sequences may affect the transcriptional
      activities of the flanking genes at the integration sites and may be a cause of
      altered local and systemic immune responses to burn-related stress.

PMID- 11971680
TI  - Postinjury enteral tolerance is reliably achieved by a standardized protocol.
AB  - BACKGROUND: Postinjury enteral nutrition (EN) is beneficial. Unfortunately,
      severely injured patients who should benefit most are frequently intolerant. To
      assist in maximizing enteral tolerance in the critically injured, we first
      implemented a prospective analysis of the effectiveness of a standardized enteral
      protocol (EP) at a single institution followed by a prospective multi
      institutional analysis of its implementation. METHODS: Tolerance parameters were
      prospectively collected on severely injured patients at a single (Phase I) and
      then multiple (Phase II) institutions. EN was begun at 15 cc/h and advanced every
      12 h to a patient specific targeted goal. Intolerance symptoms (high nasogastric
      output/emesis, abdominal distention, and diarrhea) were assessed and graded every
      12 h and managed using a standardized protocol. Tolerance was characterized as
      early (during initial advancement of feeds) or late (after standard goal) and
      classified as good (EN advanced per EP), moderate (rate decreased per EP), poor
      (EN held per EP), or EN discontinued (and TPN begun). RESULTS: In Phase I
      patients (ISS = 25 +/- 3) early tolerance was good in 82% (14/17) while late good
      tolerance decreased to 65% (11/17). In Phase II patients (ISS = 30 +/- 2), early
      tolerance was good in 85% (41/49) and late tolerance was good in 80% (39/49).
      Moderate intolerance was primarily seen in Phase II patients and due to high
      gastric output in patients fed proximal to the ligament of Treitz (13/16).
      Overall 88% (15/17) of Phase I and 100% (49/49) of Phase II patients were
      successfully maintained on EN. CONCLUSIONS: Severely injured patients exhibited
      good tolerance to EN when managed using a standardized protocol at four Level I
      trauma centers. Moderate intolerance was associated with high gastric output and
      may be lessened by feeding distal to the ligament of Treitz.

PMID- 11971681
TI  - Photoinduced charge separation reactions of J-aggregates coated on silver
      nanoparticles.
AB  - The photochemistry of cyanine J-aggregates on the surface of colloidal Ag
      nanoparticles is reported. The photochemistry is initiated through ultrafast
      photoexcitation of the plasmon band in Ag nanoparticles, producing an enhanced
      near-field that interacts with the J-aggregate monolayer. Through transient
      absorption spectroscopy, we show that photoexcitation of the plasmon in Ag
      nanoparticles leads to exciton dynamics that differ strongly from J-aggregates
      alone or for J-aggregate monolayers on bulk metal surfaces. Specifically, charge
      separated states with a lifetime of approximately 300 ps between the J-aggregate
      and Ag colloid are formed. The reduction of the Ag nanoparticles is shown to be a
      multielectron process.

PMID- 11971682
TI  - Anti-thyroid drug methimazole: X-ray characterization of two novel ionic
      disulfides obtained from its chemical oxidation by I(2).
AB  - Interaction of methimazole (MMI, 1-methyl-imidazole-2-thione) with I2 in solvents
      having different polarity gives two new stable compounds containing a dication
      disulfide and a monocation disulfide arranged in dimers, respectively. These two
      species could represent effective intermediates in the reaction of MMI with an
      active iodine species in the thyroid gland and therefore shed more light on the
      mechanism of action of MMI as an antithyroid drug.

PMID- 11971683
TI  - Hydrogenation of olefins in supercritical CO(2) catalyzed by palladium
      nanoparticles in a water-in-CO(2) microemulsion.
AB  - Nanometer-sized metallic palladium particles can be synthesized by hydrogen
      reduction of Pd2+ ions dissolved in the water core of a water-in-CO2
      microemulsion. The Pd nanoparticles, stabilized by the micromeulsion and
      uniformly dispersed in the supercritical fluid phase, are effective catalysts for
      hydrogenation of olefins. Examples of rapid and efficient hydrogenation of water
      soluble and CO2-soluble olefins catalyzed by the Pd nanoparticles in
      supercritical CO2 are given.

PMID- 11971684
TI  - 2'-hydroxypyridoxol, a biosynthetic precursor of vitamins B(6) and B(1) in yeast.
AB  - In separate experiments cultures of the yeast Saccharomyces cerevisiae ATTC 7752
      were grown in the presence of [5',5'-2H2]- or of [2',2',5',5'-2H4]-3-hydroxy
      2,4,5-tri(hydroxymethyl)pyridine (i.e., 2'-hydroxypyridoxol). The 2H NMR spectra
      of the samples of pyridoxamine dihydrochloride and of thiamin chloride
      hydrochloride that were isolated from the two experiments showed the presence of
      deuterium at the corresponding sites. Entry of deuterium from the specifically 2H
      labeled samples of 2'-hydroxypyridoxol into the predicted sites of pyridoxamine
      and of the pyrimidine unit of thiamin provides the first unequivocal evidence
      that, in yeast, 2'-hydroxypyridoxol is an intermediate on the route from a C5
      sugar into vitamin B6, and adds to the evidence that pyridoxol serves as a
      precursor of the pyrimidine unit of thiamin, supplying the C5N unit, C-2',2,N-1,C
      6,5,5' as an intact unit.

PMID- 11971685
TI  - Stereoselective recognition of an aziridine with a Co(III) complex: a potential
      transition-state analogue for catalytic epoxidation.
AB  - Reversible and stereoselective coordination of 1-(R)-phenyl-2-(S)-methylaziridine
      to (S,S)L-Co(III) and (R,R)L-Co(III) (where L represents a salen ligand obtained
      from diamino cyclohexane and 2,4-di-tert-butyl salicylaldehyde) has been
      investigated. 1H NMR data indicate that the aziridine binds about three times
      more tightly to (S,S)L-Co(III) than to (R,R)L-Co(III). Crystal structures of two
      molecules of the aziridine coordinated to the Co(III) complexes have been
      determined. These structures together with molecular mechanics computation
      provide insight into the origin of stereoselective recognition of the aziridine
      to the Co(III) complexes.

PMID- 11971686
TI  - Binding modes for the first coupled electron and proton addition to FeMoco of
      nitrogenase.
AB  - A combined broken-symmetry density functional and electrostatics approach has
      been used to model the one-electron reduced and protonated state of the iron
      molybdenum cofactor active site of nitrogenase. The active site of the protein
      contains Fe, Mo, S, N, and O atoms, and many possible sites for protonation have
      been examined. A novel hydridic proton asymmetrically located in the central
      cavity created by six Fe sites is most favored from the calculations. Under
      physiological turnover conditions of low electron flux, the formation of this
      iron-hydride intermediate may represent a first step towards cofactor liberation
      of dihydrogen in the absence of dinitrogen.

PMID- 11971687
TI  - Dyotropic rearrangement facilitated proximal functionalization and oxidative
      removal of angular methyl groups: efficient syntheses of 23'-deoxy cephalostatin
      1 analogues.
AB  - Oxidative functionalization (or removal) of a steroidal C18 methyl group is
      possible using a previously unknown dyotropic rearrangement of a seven-membered
      fused C-ring lactone to a 6-ring spiro lactone. Spiroketal equilibration led to
      the 23-deoxy South analogue of cephalostatin 1 (1) in only 12 steps (23% overall
      yield) from hecogenin acetate 4, and to strained diene South 1 analogue 30 in 11
      steps (28% overall). Total synthesis of 23'-deoxy cephalostatin 1 (3) was
      accomplished in 16 operations from 4 (9% overall; average 86% yield per
      operation), and that of 16',17'-dehydro-23'-deoxy cephalostatin 1 (36) in 15
      operations from 4 (8% overall; av 84%/op).

PMID- 11971688
TI  - Structure of 4-sila-3-platinacyclobutene and its formation via Pt-promoted gamma
      Si-H bond activation of 3-sila-1-propenylplatinum precursor.
AB  - 4-Sila-3-platinacyclobutene was isolated from the reaction of Pt(SiHPh2)2(PMe3)2
      with dimethyl acetylenedicarboxylate (DMAD) and characterized by X-ray
      crystallography. The formation pathway was found to involve gamma-Si-H bond
      activation of the 3-sila-1-propenylplatinum intermediate that is formed by the
      insertion of a DMAD into a Pt-Si bond of Pt(SiHPh2)2(PMe3)2.

PMID- 11971689
TI  - A synthesis of (+)-FR182877, featuring tandem transannular Diels-Alder reactions
      inspired by a postulated biogenesis.
AB  - An efficient biomimetic synthesis of the reported structure of the hexacyclic,
      cytotoxic secondary metabolite FR182877 is described. The successful route
      features the synthesis of a 19-membered ring carbocycle using two pi-allyl
      palladium(II)-mediated C-C bond-forming reactions. This polyunsaturated
      macrocycle undergoes tandem transannular Diels-Alder reactions that create five
      rings and seven stereogenic centers in one operation under mild conditions,
      representing the first double transannular Diels-Alder reaction. The absolute
      stereochemistry of the natural product is demonstrated to be opposite of that
      reported previously. Significant quantities of both enantiomers of this
      microtubule-stabilizing natural product and related structures are now available
      via this approach.

PMID- 11971691
TI  - Nonionic block copolymer synthesis of large-pore cubic mesoporous single crystals
      by use of inorganic salts.
AB  - Large-pore cubic (Im3m) mesoporous silica single crystals have been synthesized
      by using commercial nonionic block copolymers as templates and inorganic salts as
      additives. These single crystals possess exclusively uniform rhombdodecahedron
      shapes ( approximately 1 mum) with approximately 100% yield. The mesopore lattice
      array in each crystal face is solved by TEM, further confirming that these
      crystals are perfect single crystals.

PMID- 11971690
TI  - A chiral molecular square with metallo-corners for enantioselective sensing.
AB  - A family of chiral molecular squares based on fac-Re(CO)3Cl metallocorners and
      enantiopure atropisomeric bipyridine bridging ligands (L1-4) have been
      synthesized in high yields by refluxing ClRe(CO)5 and L1-4 in 1:1 molar ratio.
      These novel chiral metallocycles have been characterized by 1H and 13C{1H} NMR,
      UV-vis, luminescence, and circular dichroism (CD) spectroscopies, FAB mass
      spectrometry, and microanalysis. Molecular square 4 which contains four 1,1'-bi-2
      naphthol functionalities exhibits interesting enantioselective luminescence
      quenching by 2-amino-1-propanol. This research illustrates the potential of
      generating novel functional materials based on supramolecular chemistry.

PMID- 11971692
TI  - Highly enantioselective hydrosilylation of aromatic alkenes.
AB  - Currently, the most effective and economic way to convert an alkene into an
      optically active alcohol is the two-step sequence: hydrosilylation/oxidation.
      Much work has been devoted to elucidating effective catalysts for this process,
      but hitherto only one effective and highly stereoselective process has been
      available. Herein we present a novel catalytic system for the asymmetric
      hydrosilylation of aromatic alkenes, giving the products in high yields and with
      the highest enantioselectivity (up to 99% ee) ever observed for this reaction.
      The reaction works efficiently for a variety of substituted aromatic alkenes,
      giving access after Tamao oxidation to almost optically pure benzylic alcohols in
      high yields.

PMID- 11971693
TI  - Zinc(II) as a versatile template for the design of dipolar and octupolar NLO
      phores.
AB  - Thermally stable dipolar and octupolar (D2d, D3) NLO-phores are readily
      accessible by combining one, two, or three 4,4'-bis(dialkylaminostyryl)-[2,2']
      bipyridyl ligands with zinc(II) salts. The off-resonant beta0 values point out
      the superiority of octupoles versus dipoles in terms of nonlinearity/transparency
      tradeoff. The octahedral tris(bipyridyl)zinc(II) complex exhibits a very large
      beta0 value (241 x 10-30 esu), which is the largest ever reported for octupolar
      molecules.

PMID- 11971694
TI  - Metal-organic approach to binary optical memory.
AB  - Two new Ru(II) diimine chromophores, each containing a single photochromic
      dianthryl unit, have been prepared and characterized. The photoluminescence from
      the Ru(II) complexes is modulated by the photochromic action of the dianthryl
      species, which serves as a triplet energy transfer quencher in one photochromic
      state. The coupling of the dianthryl photochromic action to the Ru(II) complex
      emission permits nondestructive photoluminescence readout of binary information
      photochemically recorded on the molecular level. Luminescent images stored on
      polystyrene films that contain these molecules maintained their integrity for
      periods of months with no apparent degradation or variation in the image
      resolution, suggesting their durability for long-term storage in read-only memory
      applications.

PMID- 11971695
TI  - Crystalline boron nanowires.
AB  - Ideal nanowire interconnects for nanoelectronics will be refractory, covalently
      bonded, and highly conductive, irrespective of crystallographic orientation.
      Theoretical studies suggest that boron nanotubes should be stable and exhibit
      higher electrical conductivities than those of carbon nanotubes. We describe CVD
      growth of elemental boron nanowires, which are found to be dense nanowhiskers
      rather than nanotubes. Conductivity measurements establish that they are
      semiconducting, with electrical properties consistent with those of elemental
      boron. High conductivities should be achievable through doping.

PMID- 11971696
TI  - The first example of macrocycles containing butterfly transition metal cluster
      cores via novel tandem reactions.
AB  - A novel type of double butterfly, two mu-CO-containing dianions {[(mu
      CO)Fe2(CO)6]2[mu-SCH2(CH2OCH2)nCH2S-mu]}2- (m1, n = 2, 3), has been synthesized
      from dithiol HSCH2(CH2OCH2)nCH2SH (n = 2, 3), Fe3(CO)12, and Et3N in THF at room
      temperature. While dianions m1 react in situ with CS2 followed by treatment with
      dihalide 1,4-(BrCH2)2C6H4 or 1,4-I(CH2)4I to give macrocyclic clusters [mu
      SCH2(CH2OCH2)nCH2S-mu](mu-CS2ZCS2-mu)[Fe2(CO)6]2 (1a, n = 2, Z = 1,4-(CH2)2C6H4;
      1b, n = 3, Z = (CH2)4), reactions of dianions m1 with (mu-S2)Fe2(CO)6 followed by
      treatment with dihalide 1,4-I(CH2)4I afford macrocyclic clusters [mu
      SCH2(CH2OCH2)nCH2S-mu]{[Fe2(CO)6]2(mu4-S)}2[mu-S(CH2)4S-mu] (2a, n = 2; 2b, n =
      3). The crystal structures of 1a and 2b are described.

PMID- 11971697
TI  - Dynamics of inter- and intrastrand hole transport in DNA hairpins.
AB  - The dynamics of photoinduced electron transfer has been investigated in DNA
      hairpins possessing a stilbenedicarboxamide (Sa) electron acceptor, a guanine (G)
      primary donor, and two adjacent guanines (GG) as secondary donors. Hole transport
      from G to GG across a single A is more rapid than across AA or T by factors of 20
      +/- 7 and 40 +/- 15, respectively. Intrastrand hole transport across a single A
      is more rapid than interstrand transport by a factor of 7 +/- 3.

PMID- 11971698
TI  - 19F, (1)H-HOESY and PGSE NMR studies of neutral trinuclear complexes of Au(I) and
      Hg(II): evidence for acid-base stacking in solution.
AB  - By combining the information from 19F, 1H-HOESY and PGSE NMR methodologies,
      unprecedented direct evidence has been obtained for the formation of
      supramolecular assemblies in solution between the trinuclear cyclic AuI basic
      compounds ([Au(mu-C2,N3-bzim)]3 (bzim = 1-benzylimidazolate), 1, and [Au(mu-C,N
      C(OEt)=N-p-C6H4-CH3)]3, 2, on one hand, and the trinuclear cyclic HgII acid
      complex [Hg(mu-C,C-C6F4)]3, 3, on the other hand. HOESY experiments indicate that
      a stacking similar to that observed in the solid state occurs. PGSE studies
      demonstrate the presence of an equilibrium between the free trinuclear entities
      and adduct A in the case of 2/3 admixtures (see Sketch) while for 1/3 admixtures,
      adducts A and B are mainly present in solution.

PMID- 11971699
TI  - Cu(I)/bis(azaferrocene)-catalyzed enantioselective synthesis of beta-lactams via
      couplings of alkynes with nitrones.
AB  - As a consequence of the wide-ranging significance of beta-lactams (e.g., use as
      drugs and as chiral building blocks), a great deal of effort has been dedicated
      to the development of methods for their stereoselective synthesis. Although
      considerable progress has been achieved, nearly all of the approaches that have
      been described are based on the use of chiral precursors; direct catalytic
      enantioselective routes to beta-lactams are rare as well as limited in scope. In
      this communication, we establish that, using a new C2-symmetric planar-chiral
      bis(azaferrocene) ligand, we can generate beta-lactams with very good
      enantiomeric excess and cis diastereoselection via catalytic enantioselective
      Kinugasa reactions (couplings of alkynes with nitrones). Appealing attributes of
      this process include the ready availability of the starting materials, the
      functional-group tolerance of the reaction, and the convergency of the approach.

PMID- 11971700
TI  - Characterizing the oxygen-oxygen interaction in the dinitramide anion.
AB  - Atomic interactions between oxygen atoms have been analyzed in terms of the
      Theory of Atoms in Molecules for the biguanidium dinitramide and biguanidium bis
      dinitramide crystals. The electron density has been derived from X-ray
      diffraction data obtained at 90 K, and the potential energy density has been
      calculated using the density functional approach. Bond critical points have been
      found on the O(1)...O(4) interatomic line in both the electron density and
      potential energy density gradient fields. The bond path and its associated virial
      path have been obtained. The interaction has been identified as a bonding closed
      shell type interaction.

PMID- 11971701
TI  - Lone-pair self-containment in tellurite tubes: hydrothermal syntheses and
      structures of BaTe(3)O(7) and BaTe(4)O(9).
AB  - The hydrothermal syntheses and single-crystal structures of BaTe3O7 and BaTe4O9
      are reported. These closely related new phases, which can be regarded as the n =
      3 and 4 members of the BaTenO2n+1 family, are built up from infinite, tubular,
      columns of Te/O polyhedra (6 ring loops for BaTe3O7 and 8 ring loops for BaTe4O9)
      with barium cations completing the structures. The tubes represent a novel way to
      accommodate the lone pair of electrons associated with each TeIV species and
      suggest the possibility of redox intercalation chemistry for these types of
      material.

PMID- 11971702
TI  - Synthesis and structure of [Fe(13)O(4)F(24)(OMe)(12)](5-): the first open-shell
      Keggin ion.
AB  - The reaction between ferric fluoride trihydrate and pyridine in hot methanol
      produced yellow-brown crystals of (PyH)5.[Fe13O4F24(OMe)12].4H2O.CH3OH. The
      anionic complex [Fe13O4F24(OMe)12]5- (1), which has a full Td symmetry, is the
      first example of an open-shell Keggin ion consisting of 13 high-spin d5 iron(III)
      atoms. The central, tetrahedral {FeO4} unit in 1 is surrounded by 12 octahedral
      iron atoms, which are bridged by methoxide oxygen atoms and fluoride ligands. In
      addition, each of the 12 iron atoms is coordinated to a terminal fluoride ligand
      with an Fe-F distance of 1.846(3) A. Magnetic susceptibility studies indicate
      strong exchange interactions between the iron atoms, the mueff value of 19.3 muB
      at 300 K being significantly lower than that expected for thirteen uncoupled S =
      5/2 centers.

PMID- 11971703
TI  - Formation and reactivity of the Os(IV)-azidoimido complex,
      PPN[Os(IV)(bpy)(Cl)(3)(N(4))].
AB  - Reactions between the Os(VI)-nitrido complexes, [OsVI(L2)(Cl)3(N)] (L2 = 2,2'
      bipyridine (bpy) ([1]), 4,4'-dimethyl-2,2'-bipyridine (Me2bpy), 1,10
      phenanthroline (phen), and 4,7-diphenyl-1,10-phenanthroline (Ph2phen)), and bis
      (triphenylphosphoranylidene)ammonium azide (PPNN3) in dry CH3CN at 60 degrees C
      under N2 give the corresponding Os(IV)-azidoimido complexes, [OsIV(L2)(Cl)3(NN3)]
      (L2 = bpy = [2]-, L2 = Me2bpy = [3]-, L2 = phen = [4]-, and L2 = Ph2phen = [5]-)
      as their PPN+ salts. The formulation of the N42- ligand has been substantiated by
      15N-labeling, IR, and 15N NMR measurements. Hydroxylation of [2]- at Nalpha with
      O<--NMe3.3H2O occurs to give the Os(IV)-azidohydroxoamido complex,
      [OsIV(bpy)(Cl)3(N(OH)N3)] ([6]), which, when deprotonated, undergoes dinitrogen
      elimination to give the Os(II)-dinitrogen oxide complex, [OsII(bpy)(Cl)3(N2O)]-
      ([7]-). They are the first well-characterized examples of each kind of complex
      for Os.

PMID- 11971704
TI  - Evidence for facile atropisomerism and simple (non-nucleophilic) biradical
      forming cycloaromatization within kedarcidin chromophore aglycon.
AB  - The kinetics and thermodynamics of atropisomerism within the protected kedarcidin
      chromophore aglycon 8, as well as a series of ansa-bridged synthetic
      intermediates leading to 8, were determined by 1H NMR spectroscopy. The data show
      that the ratio of atropisomeric forms of chloropyridine-bridged ansa
      intermediates is subject to wide variation with seemingly subtle structural
      variation. The vinyl bromide 4, for example, in the first X-ray structure
      determination of a kedarcidin ansa-bridged system, was found to exist as a single
      atropisomer in the solid state, but a nearly equal mixture (K = 0.70) of isomers
      in solution (t1/2 for isomer interconversion approximately 0.2 s at 20 degrees
      C). The aglycon 8, a 2.2:1 mixture of atropisomers, was found to undergo direct
      unimolecular biradical-forming cycloaromatization at ambient temperature in a
      mixture of 1,4-cyclohexadiene-benzene, without nucleophilic activation. The
      product 9 was formed as a single atropisomer (k = 2 x 10-4 s-1, t1/2 = 58 min,
      81% yield), suggesting that the rate of atropisomerism within 8 is rapid with
      respect to cycloaromatization. The rate of cycloaromatization of 8 was found to
      be highly solvent-dependent, being more rapid in the presence of a good hydrogen
      atom donor, consistent with the earlier model studies of Hirama et al. that
      showed that certain nine-membered cyclic (Z)-enediynes may equilibrate with their
      biradical cycloaromatization products. Incubation of 8 with beta-mercaptoethanol,
      under conditions mimicking experiments leading to DNA cleavage with kedarcidin,
      showed no evidence for nucleophilic activation. The product of direct
      cycloaromatization (9) was isolated instead. The evidence suggests that
      kedarcidin, like the enediyne agent C-1027, is capable of spontaneous thermal
      biradical formation without prior chemical activation.

PMID- 11971705
TI  - Targeting cell surface receptors with ligand-conjugated nanocrystals.
AB  - To explore the potential for use of ligand-conjugated nanocrystals to target cell
      surface receptors, ion channels, and transporters, we explored the ability of
      serotonin-labeled CdSe nanocrystals (SNACs) to interact with antidepressant
      sensitive, human and Drosophila serotonin transporters (hSERT, dSERT) expressed
      in HeLa and HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found to
      dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT,
      with an estimated half-maximal activity (EC(50)) of 33 (dSERT) and 99 microM
      (hSERT). When serotonin was conjugated to the nanocrystal through a linker arm
      (LSNACs), the EC(50) for hSERT was determined to be 115 microM. Electrophysiology
      measurements indicated that LSNACs did not elicit currents from the serotonin-3
      (5HT(3)) receptor but did produce currents when exposed to the transporter, which
      are similar to those elicited by antagonists. Moreover, fluorescent LSNACs were
      found to label SERT-transfected cells but did not label either nontransfected
      cells or transfected cells coincubated with the high-affinity SERT antagonist
      paroxetine. These findings support further consideration of ligand-conjugated
      nanocrystals as versatile probes of membrane proteins in living cells.

PMID- 11971706
TI  - Identification of the metal ion binding site on an RNA motif from hammerhead
      ribozymes using (15)N NMR spectroscopy.
AB  - An RNA oligomer, r(GGACGAGUCC), which mimics the metal ion-binding motif of
      hammerhead ribozymes, was shown to fold by itself into a conformation possessing
      a metal ion binding property which is similar to that of the intact ribozyme
      (Tanaka, et al. J. Am. Chem. Soc. 2000, 122, 11303-11310). To determine the metal
      ion-binding site of this motif at an atomic level, we synthesized a series of RNA
      oligomers which were selectively labeled with a (15)N-labeled guanosine at each
      of the four guanosine residues. The (15)N-chemical shift perturbation with Cd(II)
      ions by one-dimensional (1D) (15)N NMR spectra showed that the chemical shift of
      the N7 of the G7 residue, N7/G7, in the metal ion-binding motif was specifically
      perturbed. This is the first experimental evidence to prove that the N7/G7 binds
      with a Cd(II) ion.

PMID- 11971707
TI  - Spectroscopic studies of 1-aminocyclopropane-1-carboxylic acid oxidase: molecular
      mechanism and CO(2) activation in the biosynthesis of ethylene.
AB  - 1-Aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACCO) catalyzes the last
      step in the biosynthesis of the gaseous plant hormone ethylene, which is involved
      in development, including germination, fruit ripening, and senescence. ACCO is a
      mononuclear non-heme ferrous enzyme that couples the oxidation of the cosubstrate
      ascorbate to the oxidation of substrate ACC by dioxygen. In addition to substrate
      and cosubstrate, ACCO requires the activator CO(2) for continuous turnover. NIR
      circular dichroism and magnetic circular dichroism spectroscopies have been used
      to probe the geometric and electronic structure of the ferrous active site in
      ACCO to obtain molecular-level insight into its catalytic mechanism. Resting
      ACCO/Fe(II) is coordinatively saturated (six-coordinate). In the presence of
      CO(2), one ferrous ligand is displaced to yield a five-coordinate site only when
      both the substrate ACC and cosubstrate ascorbate are bound to the enzyme. The
      open coordination position allows rapid O(2) activation for the oxidation of both
      substrates. In the absence of CO(2), ACC binding alone converts the site to five
      coordinate, which would react with O(2) in the absence of ascorbate and quickly
      deactivate the enzyme. These studies show that ACCO employs a general strategy
      similar to other non-heme iron enzymes in terms of opening iron coordination
      sites at the appropriate time in the reaction cycle and define the role of CO(2)
      as stabilizing the six-coordinate ACCO/Fe(II)/ACC complex, thus preventing the
      uncoupled reaction that inactivates the enzyme.

PMID- 11971708
TI  - DNA conformational switches as sensitive electronic sensors of analytes.
AB  - The electrical conductivity of DNA is dependent on its conformational state. We
      demonstrate here that such a dependence may be harnessed for the electronic
      sensing of external analytes, for instance, adenosine. Such a DNA sensor
      incorporates an analyte "receptor", whose altered conformation in the presence of
      bound analyte switches the conformation, and hence, the conductive path between
      two DNA double-helical stems. Two distinct designs for such sensors are described
      here, that permit significant electrical conduction through a "detector" double
      helical stem only in the presence of the bound analyte. In the first design,
      current flows through the analyte receptor itself, whereas in the second, current
      flows in a path adjacent to the receptor. The former design may be especially
      suitable for certain categories of analytes, including heterocycle-containing
      compounds such as adenosine, whereas the latter design should be generally
      applicable to the detection of any molecular analyte, large or small. Since
      analyte detection in these DNA sensors is electronic, the potential exists for
      their application in rapid and automated chip-based detection of small molecules
      as well as of proteins and other macromolecules.

PMID- 11971709
TI  - In vitro selection of ATP-binding receptors using a ribonucleopeptide complex.
AB  - A recently described three-dimensional structure of the ribosome provides a sense
      of remarkable diversity of RNA-protein complexes. We have designed a new class of
      scaffold for artificial receptors, in which a short peptide and RNA with a
      randomized nucleotide region form a stable and specific complex. The randomized
      nucleotide region was placed next to the HIV-1 Rev response element to enable the
      formation of "ribonucleopeptide" pools in the presence of the Rev peptide. In
      vitro selection of RNA oligonucleotides from the randomized pool afforded a
      ribonucleopeptide receptor specific for ATP. The ATP-binding ribonucleopeptide
      did not share the known consensus nucleotide sequence for ATP aptamers and
      completely lost its ATP-binding ability in the absence of the Rev peptide. The
      ATP-binding activity of the ribonucleopeptide was increased by a substitution of
      the N-terminal amino acid of the Rev peptide. These results demonstrate directly
      that the peptide is incorporated in the functional structure of RNA and suggest
      that amino acids outside the RNA-binding region of the peptide modulate the ATP
      binding of ribonucleopeptide. Our approach would provide an alternative strategy
      for the design of "tailor-made" ribonucleopeptide receptors and enzymes.

PMID- 11971710
TI  - Retention of configuration in the action of human plasma 3'-exonuclease on
      oligo(deoxynucleoside phosphorothioate). A new method for assignment of absolute
      configuration at phosphorus in isotopomeric deoxyadenosine 5'-O
      [(18)O]phosphorothioate.
AB  - A new method of analysis has allowed the exonucleolytic cleavage by human 3'
      exonuclease to be determined. Hydrolysis by human plasma 3'-exonuclease proceeds
      with retention of configuration at phosphorus. The new method determines the
      sense of chirality at phosphorus in isotopomeric adenosine 5'-O
      [(18)O]phosphorothioates. This is based on stereospecific two-step conversion of
      the mono-thionucleotide into the corresponding deoxyadenosine 5'-O-alpha
      [(18)O]thiotriphosphate, followed by the use of terminal deoxyribonucleotidyl
      transferase and MALDI TOF mass spectrometry of the resulting elongated primer.
      Retention of configuration in the reaction of plasma 3'-exonuclease implies a two
      step mechanism with two displacements on phosphorus. Inversion at each step leads
      to overall retention.

PMID- 11971711
TI  - An efficient approach to Aspidosperma alkaloids via [4 + 2] cycloadditions of
      aminosiloxydienes: stereocontrolled total synthesis of (+/-)-tabersonine. Gram
      scale catalytic asymmetric syntheses of (+)-tabersonine and (+)-16
      methoxytabersonine. Asymmetric syntheses of (+)-aspidospermidine and (-)
      quebrachamine.
AB  - Described is a concise, highly stereocontrolled strategy to the Aspidosperma
      family of indole alkaloids, one that is readily adapted to the asymmetric
      synthesis of these compounds. The strategy is demonstrated by the total synthesis
      of (+/-)-tabersonine (rac-1), proceeding through a 12-step sequence. The basis
      for this approach was provided by a highly regio- and stereoselective [4 + 2]
      cycloaddition of 2-ethylacrolein with 1-amino-3-siloxydiene developed in our
      laboratory. Subsequent elaboration of the initial adduct into the
      hexahydroquinoline DE ring system was accomplished efficiently by a ring-closing
      olefin metathesis reaction. A novel ortho nitrophenylation of an enol silyl ether
      with (o-nitrophenyl)phenyliodonium fluoride was developed to achieve an
      efficient, regioselective introduction of the requisite indole moiety. The final
      high-yielding conversion of the ABDE tetracycle into pentacyclic target rac-1
      relied on intramolecular indole alkylation and regioselective C
      carbomethoxylation. Our approach differs strategically from previous routes and
      contains built-in flexibility necessary to access many other members of the
      Aspidosperma family of indole alkaloids. The versatility of the synthetic
      strategy was illustrated through the asymmetric syntheses of the following
      Aspidosperma alkaloids: (+)-aspidospermidine, (-)-quebrachamine, (-)
      dehydroquebrachamine, (+)-tabersonine, and (+)-16-methoxytabersonine. Of these,
      (+)-tabersonine and (+)-16-methoxytabersonine were synthesized in greater than 1
      g quantities and in enantiomerically enriched form ( approximately 95% ee). The
      pivotal asymmetry-introducing step was a catalyzed enantioselective Diels-Alder
      reaction, which proceeded to afford the cycloadducts in up to 95% ee.
      Significantly, the synthetic sequence was easy to execute and required only four
      purifications over the 12-step synthetic route.

PMID- 11971712
TI  - Extending synthetic access to proteins with a removable acyl transfer auxiliary.
AB  - A chemo- and regioselective auxiliary-mediated peptide ligation has been
      developed that is effective under nonidealized conditions for the synthesis of
      proteins. This general amide bond ligation utilizes a removable auxiliary that is
      analogous to the role of cysteine in native chemical ligation, combining
      chemoselective thioester exchange with efficient regioselective intramolecular
      acyl transfer. Acid lability and improved ligation efficiency were introduced
      into the 2-mercaptobenzyl auxiliary by increasing the electron density of the
      aromatic ring. The 62 amino acid SH3 domain from alpha-spectrin was synthesized
      using the auxiliary-mediated ligation at a Lys-Gly sequence. The auxiliary was
      removed with TFA and scavengers from the ligated product. This methodology
      enables unprotected peptides to be coupled at noncysteine ligation sites
      expanding the scope of protein synthesis and semisynthesis.

PMID- 11971713
TI  - Remarkable structures of cyclotri(deoxycholate) and cyclotetra(24-norcholate)
      acetate esters.
AB  - X-ray crystallographic determinations and AM1 calculations have defined the solid
      state and gas-phase structures of cyclotri(deoxycholate) and cyclotetra(24
      norcholate). The latter cyclotetramer is one of the largest open macrocycles ever
      subjected to crystallography.

PMID- 11971714
TI  - Cooperative self-assembly of dendrimers via pseudorotaxane formation from a
      homotritopic guest molecule and complementary monotopic host dendrons.
AB  - Interaction of the homotritopic guest 1,3,5-tris[p
      (benzylammoniomethyl)phenyl]benzene tris(hexafluorophosphate) (1a) with dibenzo
      24-crown-8 (DB24C8) leads to the sequential self-assembly of [2]-, [3]-, and [4]
      pseudorotaxanes 7a, 8a, and 9a, respectively. The self-assembly processes were
      studied using NMR spectroscopy. In CD(3)CN and CD(3)COCD(3) the individual
      association constants K(1), K(2), and K(3) for 1:1, 1:2, and 1:3 complexes were
      determined by several methods. Via Scatchard plots, the three NH(2)(+) sites of
      1a were shown to behave independently in binding DB24C8. K values (4.4 x 10(2),
      1.4 x 10(2), and 41 M(-)(1), respectively, in CD(3)CN) directly determined from
      signals for the individual complexes (7a, 8a, and 9a) were somewhat higher than
      those estimated from the Scatchard plot because of concentration dependence, but
      the ratios of association constants followed the expected statistical order
      (K(1):K(2):K(3) = 3:1:(1)/(3)). These are believed to be the first evaluations of
      association constants leading to a [4]-pseudorotaxane. In the less polar CDCl(3),
      association constants could not be determined because approximately 90% of the
      dissolved tritopic guest, which by itself is insoluble, was present as the fully
      loaded [4]pseudorotaxane 9a! Self-assembly of homotritopic guest 1a with benzyl
      ether dendrons of the first, second, and third generations functionalized at the
      "focal point" with DB24C8 moieties (3-5) produces pseudorotaxane dendrimers. The
      self-assembly processes were studied using (1)H NMR spectroscopy. In CD(3)COCD(3)
      for all three generations the individual association constants K(1), K(2), and
      K(3) for [2]-, [3]-, and [4]-pseudorotaxane complexes 7c-e, 8c-e, and 9c-e
      indicated that the self-assembly was cooperative; that is, the ratios of the
      individual association constants exceeded the expected statistical ratios.
      Scatchard plots confirmed this behavior. Self-assembly processes in the less
      polar CDCl(3) were kinetically slow, requiring ca. 1, 2, and 3 days,
      respectively, for the first, second, and third generation systems to reach
      equilibrium with 1a; the slow rate is attributed to the insolubility of the
      homotritopic guest 1a in this medium and the steric demands of the resulting
      dendrimers. However, only dendrimers of 1:3 stoichiometry, that is, the
      nanoscopic [4]pseudorotaxanes 9, were formed! Moreover, it is noteworthy that the
      extent of dissolution of 1a (reflective of the overall association constant which
      is too high to measure) increases with generation number, presumably because of
      the more effective screening of the ionic guest by the larger dendrons and
      perhaps favorable pi-pi and CH-pi interactions. Such cooperative effects suggest
      a number of applications that can take advantage of the pH-switchable nature of
      these self-assembly processes.

PMID- 11971715
TI  - 7-N-(mercaptoalkyl)mitomycins: implications of cyclization for drug function.
AB  - The Kyowa Hakko Kogyo and Bristol-Myers Squibb companies reported that select
      mitomycin C(7) aminoethylene disulfides displayed improved pharmacological
      profiles compared with mitomycin C (1). Mechanisms have been advanced for these
      mitomycins that differ from 1. Central to many of these hypotheses is the
      intermediate generation of 7-N-(2-mercaptoethyl)mitomycin C (5). Thiol 5 has been
      neither isolated nor characterized. Two efficient methods were developed for
      mitomycin (porfiromycin) C(7)-substituted thiols. In the first method, the thiol
      was produced by a thiol-mediated disulfide exchange process using an activated
      mixed mitomycin disulfide. In the second route, the thiol was generated by base
      mediated cleavage of a porfiromycin C(7)-substituted thiol ester. We selected
      four thiols, 7-N-(2-mercaptoethyl)mitomycin C (5), 7-N-(2
      mercaptoethyl)porfiromycin (12), 7-N-(2-mercapto-2-methylpropyl)mitomycin C (13),
      and 7-N-(3-mercaptopropyl)porfiromycin (14), for study. Thiols 5 and 12-14
      differed in the composition of the alkyl linker that bridged the thiol with the
      mitomycin (porfiromycin) C(7) amino substituent. Thiol generation was documented
      by HPLC and spectroscopic studies and by thiol-trapping experiments. The linker
      affected the structure of the thiol species and the stability of the thiol. We
      observed that thiols 5 and 12 existed largely as their cyclic isomers. Evidence
      is presented that cyclization predominantly occurred at the mitomycin C(7)
      position. Correspondingly, alkyl linker substitution (13) or extension of the
      linker to three carbons (14) led to enhanced thiol stability and the predominant
      formation of the free thiol species. The dominant reaction of thiols 5 and 12-14
      or their isomers was dimerization, and we found no evidence that thiol formation
      led to mitosene production and aziridine ring-opening. These findings indicated
      that thiol generation was not sufficient for mitomycin ring activation. The
      potential pharmacological advantages of mitomycin C(7) aminoethylene disulfides
      compared with 1 is discussed in light of the observed thiol cyclization pathway.

PMID- 11971716
TI  - Stilbazulenyl nitrone (STAZN): a nitronyl-substituted hydrocarbon with the
      potency of classical phenolic chain-breaking antioxidants.
AB  - Stilbazulenyl nitrone (STAZN), 8, a nitronyl-substituted hydrocarbon, is a novel
      second-generation azulenyl nitrone with significantly enhanced potency as a chain
      breaking antioxidant vs conventional alpha-phenyl nitrones previously
      investigated as antioxidant therapeutics. A convenient (1)H NMR-based assay for
      assessing the potency of chain-breaking antioxidants has shown that STAZN is ca.
      300 times more potent in inhibiting the free radical-mediated aerobic
      peroxidation of cumene than is PBN and the experimental stroke drug NXY-059. Such
      levels of antioxidant efficacy are unprecedented among archetypal alpha-phenyl
      nitrone spin traps. Furthermore, STAZN outperforms such classical phenolic
      antioxidants as BHT and probucol and rivals the antioxidant potency of Vitamin E
      in a polar medium comprised of 80% cumene and 20% methanol. The Volodarskii
      electron-transfer mechanism involving the intermediacy of the STAZN radical
      cation has been implicated in attempts to ascertain the basis for the increased
      potency of STAZN over the three alpha-phenyl nitrones PBN, S-PBN, and NXY-059.

PMID- 11971717
TI  - Self-assembled, helically stacked anionic aggregates of 2,5,8,11-tetra-tert
      butylcycloocta[1,2,3,4-def;5,6,7,8-d'e'f']bisbiphenylene, stabilized by
      electrostatic interactions.
AB  - Tetraanions of alkyl-substituted derivatives of cycloocta[1,2,3,4-def;5,6,7,8
      d'e'f']bisbiphenylene (BPD) and their counter lithium cations self-assemble to
      form helically stacked assemblies, including a dimer, a trimer, and a tetramer.
      NMR self-diffusion measurements and unprecedented magnetic shielding effects for
      the sandwiched lithium cations support their aggregated nature. The D(2)-tetramer
      assembly is fully characterized by NMR spectroscopy, providing unequivocal
      evidence for a helix of four tetraanionic BPD layers with an estimated relative
      twist angle of about 45 degrees and interlayer spacing of ca. 4 A. The barrier
      for racemization through the in-plane inter-deck rotation is DeltaG(200)= 9.5 +/-
      0.2 kcal mol(-1) in the dimer compared to >15 kcal mol(-1) in the tetramer.

PMID- 11971718
TI  - Mechanistic insights into the photochromism of trans-10b,10c-dimethyl-10b,10c
      dihydropyrene derivatives.
AB  - A series of dimethyldihydropyrene derivatives was studied to elucidate the
      photochemical mechanism associated with the switching between the
      dimethyldihydropyrene (DHP, closed) and metacyclophanediene (CPD, open) forms of
      the molecule. Quantum yields of ring opening and closure, fluorescence quantum
      yields and lifetimes, as well as laser flash photolysis studies were performed to
      establish the effect of substituents on the switching efficiency. Ring opening of
      the DHPs occurs from the first singlet excited state. The low quantum yields for
      the ring opening reaction observed (< or =0.042) are a consequence of the low
      rate constant (< or =1.7 x 10(7) s(-1)) for this process. The quantum yields for
      ring closure of the CPD were determined for select compounds and were of the
      order of 0.1-0.4. These results show that the efficiency for ring opening of this
      class of compounds is intrinsically low, but can be modulated to some extent by
      the introduction of substituents. These properties should be taken into account
      when considering what type of photoswitching devices DHPs might be useful for.

PMID- 11971719
TI  - Molecular compasses and gyroscopes. II. Synthesis and characterization of
      molecular rotors with axially substituted bis[2-(9-triptycyl)ethynyl]arenes.
AB  - We have developed a simple convergent procedure for the synthesis of molecular
      rotors consisting of a central aromatic group coupled with two axially positioned
      ethynyltriptycenes. Molecular rotors with 1,4-phenylene (1), 1,4'-1,1'
      biphenylene (2), 9,10-anthracenylene (3), and 2,7-pyrenylene (4) groups were
      prepared by Pd(0)-catalyzed coupling of ethynyl triptycenes with the
      corresponding dibromoarenes. Although compounds 1-4 were not expected to have
      free rotation in the solid state, the rotational potentials of 1 and 3 were
      analyzed by semiempirical methods and the crystal packing of 1 was analyzed to
      design the structures most likely to yield a functional rotor in the solid state.
      Semiempirical PM3 calculations predict compounds 1, 2, and 4 to have frictionless
      internal rotation even at temperatures as low as 25 K, while compound 3 is
      expected to have a barrier of ca. 4 kcal/mol.

PMID- 11971720
TI  - Thermodynamics, kinetics, and dynamics of the two alternative aniomesolytic
      fragmentations of C-O bonds: an electrochemical and theoretical study.
AB  - Fragmentation reactions of radical anions (mesolytic cleavages) of cyanobenzyl
      alkyl ethers (intramolecular dissociative electron transfer, heterolytic
      cleavages) have been studied electrochemically. The intrinsic barriers for the
      processes have been established from the experimental thermodynamic and kinetic
      parameters. These values are more than 3 kcal/mol lower as an average than the
      related homolytic mesolytic fragmentations of radical anions of 4-cyanophenyl
      ethers. In the particular case of isomers 4-cyanobenzyl phenyl ether and 4
      cyanophenyl benzyl ether, the difference in intrinsic barriers amounts to 5.5
      kcal/mol, and this produces an energetic crossing where the thermodynamically
      more favorable process (homolytic) is the kinetically slower one. The fundamental
      reasons for this behavior have been established by means of theoretical
      calculations within the density functional theory framework, showing that, in
      this case, the factors that determine the kinetics are clearly different (mainly
      present in the transition state) from those that determine the thermodynamics and
      they are not related to the regioconservation of the spin density ("spin
      regioconservation principle"). Our theoretical results reproduce quite well the
      experimental energetic difference of barriers and demonstrate the main structural
      origin of the difference.

PMID- 11971722
TI  - A comprehensive investigation of the chemistry and basicity of a parent
      amidoruthenium complex.
AB  - trans-(DMPE)(2)Ru(H)(NH(2)) (1) dehydrogenates cyclohexadiene and 9,10
      dihydroanthracene to yield benzene (or anthracene), (DMPE)(2)Ru(H)(2), and
      ammonia. Addition of fluorene to 1 results in the formation of the ion pair
      [trans-(DMPE)(2)Ru(H)(NH(3))(+)][A(-)] (A(-) = fluorenide, 4a). Complex 1 also
      reacts with weak acids A-H (A-H = phenylacetylene, 1,2-propadiene,
      phenylacetonitrile, 4-(alpha,alpha,alpha-trifluoromethyl)phenylacetonitrile,
      cyclobutanone, phenol, p-cresol, aniline) to form ammonia and trans
      (DMPE)(2)Ru(H)(A) (7, 8, 9a, 9b, 10, 11b, 11c, 12, respectively). In the cases
      where A-H = phenylacetylene, cyclobutanone, aniline, phenol, and p-cresol, the
      reaction was observed to proceed via ion pairs analogous to 4a. Compound 1 is
      reactive toward even weaker acids such as toluene, propylene, ammonia,
      cycloheptatriene, and dihydrogen, but in these cases deuterium labeling studies
      revealed that only H/D exchange between A-H and the ND(2) group is observed,
      rather than detectable formation of ion pairs or displacement products. Addition
      of triphenylmethane to 1 results in the formation of an equilibrium mixture of 1,
      triphenylmethane, and the ruthenium/triphenylmethide ion pair 4h. If the
      energetics of ion-pair association are ignored, this result indicates that the
      basicity of 1 is similar to that of triphenylmethide. All these observations
      support the conclusion that the NH(2) group in amido complex 1 is exceptionally
      basic and as a result prefers to abstract a proton rather than a hydrogen atom
      from a reactive C-H bond. The energetics and mechanism of these proton-transfer
      and -exchange reactions are analyzed with the help of DFT calculations.

PMID- 11971721
TI  - Total synthesis of A-315675: a potent inhibitor of influenza neuraminidase.
AB  - A concise, stereocontrolled, and practical synthesis of a neuraminidase inhibitor
      consisting of a highly functionalized D-proline scaffold is described. Key
      features involve a stereocontrolled addition of a propiolate ester to a chiral
      nonracemic nitrone derived originally from D-serine and the manipulation of
      acyclic and cyclic motifs en route to the target in 12.8% overall yield over 22
      steps. Several crystalline intermediates were suitable for single-crystal X-ray
      analysis.

PMID- 11971723
TI  - A novel isomerization on interaction of antitumor-active azole-bridged dinuclear
      platinum(II) complexes with 9-ethylguanine. Platinum(II) atom migration from N2
      to N3 on 1,2,3-triazole.
AB  - The reactions of the dinuclear platinum(II) complexes, [[cis-Pt(NH(3))(2)](2)(mu
      OH)(mu-pz)](NO(3))(2) (1, pz = pyrazolate), [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu
      1,2,3-ta-N1,N2)](NO(3))(2) (2, 1,2,3-ta = 1,2,3-triazolate), and a newly prepared
      [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-4-phe-1,2,3-ta-N1,N2)](NO(3))(2) (3, 4-phe-1,2,3
      ta = 4-phenyl-1,2,3-triazolate), whose crystal structure was determined, with 9
      ethylguanine (9EtG) have been monitored in aqueous solution at 310 K by means of
      (1)H NMR spectroscopy. The dinuclear platinum(II) complexes 1-3 each react with
      9EtG in a bifunctional way to form 1:2 complexes, [[cis-Pt(NH(3))(2)(9EtG
      N7)](2)(mu-pz)](3+) (4), [[cis-Pt(NH(3))(2)(9EtG-N7)](2)(mu-1,2,3-ta-N1,N3)](3+)
      (5), and [[cis-Pt(NH(3))(2)(9EtG-N7)](2)(mu-4-phe-1,2,3-ta-N1,N3)](3+) (6). The
      reactions of 2 and 3 involve a novel isomerization, in which the Pt atom,
      initially bound to N2 on the 1,2,3-ta, migrates to N3 after the first
      substitution by N7 of 9EtG. This isomerization reaction has been unambiguously
      characterized by 1D and 2D NMR spectroscopy and pH titration. The reactions of 2
      and 3 with 9EtG show faster kinetics, and the second-order rate constants (k) for
      the reactions of 1-3are 1.57 x 10(-4), 2.53 x 10(-4), and 2.56 x 10(-4) M(-1) s(
      1), respectively. The pK(a) values at the N1H site of 9EtG were determined for 4
      6 from the pH titration curves. Cytotoxicity assays of 1-3 were performed in
      L1210 murine leukemia cell lines, respectively sensitive and resistant to
      cisplatin. In the parent cell line, 2 and 3 exhibit higher cytotoxicity compared
      to cisplatin, especially, 2 is 10 times as active as cisplatin. 1 was found to be
      less cytotoxic than cisplatin, but still in the active range and more active than
      cisplatin in a cisplatin-resistant cell line.

PMID- 11971724
TI  - Alkali metal intercalated fullerene-like MS(2) (M = W, Mo) nanoparticles and
      their properties.
AB  - Layered metal disulfides-MS(2) (M = Mo, W) in the form of fullerene-like
      nanoparticles and in the form of platelets (crystallites of the 2H polytype) have
      been intercalated by exposure to alkali metal (potassium and sodium) vapor using
      a two-zone transport method. The composition of the intercalated systems was
      established using X-ray energy dispersive spectrometer and X-ray photoelectron
      spectroscopy (XPS). The alkali metal concentration in the host lattice was found
      to depend on the kind of sample and the experimental conditions. Furthermore, an
      inhomogeneity of the intercalated samples was observed. The product consisted of
      both nonintercalated and intercalated phases. X-ray diffraction analysis and
      transmission electron microscopy of the samples, which were not exposed to the
      ambient atmosphere, showed that they suffered little change in their lattice
      parameters. On the other hand, after exposure to ambient atmosphere, substantial
      increase in the interplanar spacing (3-5 A) was observed for the intercalated
      phases. Insertion of one to two water molecules per intercalated metal atom was
      suggested as a possible explanation for this large expansion along the c-axis.
      Deintercalation of the hydrated alkali atoms and restacking of the MS(2) layers
      was observed in all the samples after prolonged exposure to the atmosphere.
      Electric field induced deintercalation of the alkali metal atoms from the host
      lattice was also observed by means of the XPS technique. Magnetic moment
      measurements for all the samples indicate a diamagnetic to paramagnetic
      transition after intercalation. Measurements of the transport properties reveal a
      semiconductor to metal transition for the heavily K intercalated 2H-MoS(2). Other
      samples show several orders of magnitude decrease in resistivity and two- to five
      fold decrease in activation energies upon intercalation. These modifications are
      believed to occur via charge transfer from the alkali metal to the conduction
      band of the host lattice. Recovery of the pristine compound properties
      (diamagnetism and semiconductivity) was observed as a result of deintercalation.

PMID- 11971725
TI  - Palladium(II) complexes, as synthetic peptidases, regioselectively cleave the
      second peptide bond "upstream" from methionine and histidine side chains.
AB  - Palladium(II) complexes promote hydrolysis of natural and synthetic oligopeptides
      with unprecedented regioselectivity; the only cleavage site is the second peptide
      bond upstream from a methionine or a histidine side chain, that is, the bond
      involving the amino group of the residue that precedes this side chain. We
      investigate this regioselectivity with four N-acetylated peptides as substrates:
      neurotransmitter methionine enkephalin (Ac-Tyr-Gly-Gly-Phe-Met) and synthetic
      peptides termed Met-peptide (Ac-Ala-Lys-Tyr-Gly-Gly-Met-Ala-Ala-Arg-Ala), His
      peptide (Ac-Val-Lys-Gly-Gly-His-Ala-Lys-Tyr-Gly-Gly-Met(OX)-Ala-Ala-Arg-Ala), in
      which a Met is oxidized to sulfone, and HisMet-peptide (Ac-Val-Lys-Gly-Gly-His
      Ala-Lys-Tyr-Gly-Gly-Met-Ala-Ala-Arg-Ala). While maintaining protein-like
      properties, these substrates are suitable for quantitative study since their
      coordination to Pd(II) ion can be determined (by NMR spectroscopy), and the
      cleavage fragments can be separated (by HPLC methods) and identified (by MALDI
      mass spectrometry). The only peptide bonds cleaved were the Gly3-Phe4 bond in
      methionine enkephalin, Gly4-Gly5 bond in Met-peptide, Gly3-Gly4 in His-peptide,
      and Gly3-Gly4 and Gly9-Gly10 bonds in HisMet-peptide. We explain this consistent
      regioselectivity of cleavage by studying the modes of Met-peptide coordination to
      the Pd(II) ion in [Pd(H(2)O)(4)](2+) complex. In acidic solution, the rapid
      attachment of the Pd(II) complex to the methionine side chain is followed by the
      interaction of the Pd(II) ion with the peptide backbone upstream from the anchor.
      In the hydrolytically active complex, Met-peptide is coordinated to Pd(II) ion as
      a bidentate ligand - via sulfur atom in the methionine side chain and the first
      peptide nitrogen upstream from this anchor - so that the Pd(II) complex
      approaches the scissile peptide bond. Because the increased acidity favors this
      hydrolytically active complex, the rate of cleavage guided by either histidine or
      methionine anchor increased as pH was lowered from 4.5 to 0.5. The unwanted
      additional cleavage of the first peptide bond upstream from the anchor is
      suppressed if pH is kept above 1.2. Four Pd(II) complexes cleave Met-peptide with
      the same regioselectivity but at somewhat different rates. Complexes in which
      Pd(II) ion carries labile ligands, such as [Pd(H(2)O)(4)](2+) and
      [Pd(NH(3))(4)](2+), are more reactive than those containing anionic ligands, such
      as [PdCl(4)](2)(-), or a bidentate ligand, such as cis-[Pd(en)(H(2)O)(2)](2+).
      When both methionine and histidine residues are present in the same substrate, as
      in HisMet-peptide, 1 molar equivalent of the Pd(II) complex distributes itself
      evenly at both anchors and provides partial cleavage, whereas 2 molar equivalents
      of the promoter completely cleave the second peptide bond upstream from each of
      the anchors. The results of this study bode well for growing use of palladium(II)
      reagents in biochemical and bioanalytical practice.

PMID- 11971726
TI  - Synthesis of trithiolanes and tetrathianes from thiiranes catalyzed by ruthenium
      salen nitrosyl complexes.
AB  - The compound [Ru(salen)(NO)(H(2)O)](SbF(6)) (1) (salen = N,N'-ethylene-bis
      salicylidene aminate) reacts catalytically with thiiranes and converts them to
      olefins and 1,2,3,4-tetrathianes or 1,2,3-trithiolanes. The monosubstituted
      thiiranes styrene sulfide and propylene sulfide reacted to form the corresponding
      olefin and the 4-substituted 1,2,3-trithiolane in a 2:1 ratio in isolated yields
      in excess of 90%. The disubstituted thiirane cis-stilbene sulfide was converted
      to cis-stilbene and 5,6-trans-1,2,3,4-diphenyltetrathiane in a 3:1 ratio in the
      presence of a catalytic amount of 1 in CD(3)NO(2). Coordination of cis-stilbene
      sulfide to the salen complex in a ligand substitution reaction was established by
      isolation of [Ru(salen)(NO)(cis-stilbene sulfide)](SbF(6)) (6). (1)H NMR studies
      performed on 6 indicated that the salen macrocycle had rearranged upon thiirane
      coordination. A similar rearrangement was found to be stabilized by other ligands
      including tetramethylethylene sulfide, tetrahydrothiophene, and d(3)
      acetonitrile. The alpha-deuterio-cis-stilbene sulfide catalyst adduct (d-6)
      reacted with unlabeled cis-stilbene sulfide to form deuterium-labeled trans
      diphenyl-tetrathiane and unlabeled cis-stilbene as shown by GCMS and (1)H NMR.
      Thus, the solution thiirane behaves as a sulfur donor and forms olefin, whereas
      the coordinated thiirane becomes the cyclic polysulfide. beta-cis-Deuteriostyrene
      sulfide was used to show that ring closure to form cyclic polysulfide
      incorporated inversion of stereochemistry versus starting thiirane. A mechanism
      for catalysis consistent with experimental data is presented that requires
      coordination of thiirane to the metal complex followed by bimolecular attack of
      free thiirane on the coordinated thiirane.

PMID- 11971727
TI  - The [Sn(9)Pt(2)(PPh(3))](2)(-) and [Sn(9)Ni(2)(CO)](3)(-) complexes: two markedly
      different Sn(9)M(2)L transition metal zintl ion clusters and their dynamic
      behavior.
AB  - [Sn(9)Pt(2)(PPh(3))](2)(-) (2) was prepared from Pt(PPh(3))(4), K(4)Sn(9), and
      2,2,2-cryptand in en/toluene solvent mixtures. The [K(2,2,2-cryptand)](+) salt is
      very air and moisture sensitive and has been characterized by ESI-MS, variable
      temperature (119)Sn, (31)P, and (195)Pt NMR and single-crystal X-ray diffraction
      studies. The structure of 2 comprises an elongated tricapped Sn(9) trigonal prism
      with a capping PtPPh(3), an interstitial Pt atom, a hypercloso electron count (10
      vertex, 20 electron) and C(3)(v)() point symmetry. Hydrogenation trapping
      experiments and deuterium labeling studies showed that the formation of 2
      involves a double C-H activation of solvent molecules (en or DMSO) with the
      elimination of H(2) gas. The ESI-MS analysis of 2 showed the
      K[Sn(9)Pt(2)(PPh(3))](1)(-) parent ion, an oxidized [Sn(9)Pt(2)(PPh(3))](1)(-)
      ion, and the protonated binary cluster anion [HSn(9)Pt(2)](1)(-). 2 is highly
      fluxional in solution giving rise to a single time-averaged (119)Sn NMR signal
      for all nine Sn atoms but the Pt atoms remain distinct. The exchange is
      intramolecular and is consistent with a rigid, linear Pt-Pt-PPh(3) rod embedded
      in a liquidlike Sn(9) matrix. [Sn(9)Ni(2)(CO)](3)(-) (3) was prepared from
      Ni(CO)(2)(PPh(3))(2), K(4)Sn(9), and 2,2,2-cryptand in en/toluene solvent
      mixtures. The [K(2,2,2-cryptand)](+) salt is very air and moisture sensitive, is
      paramagnetic, and has been characterized by ESI-MS, EPR, and single-crystal X-ray
      diffraction. Complex 3 is a 10-vertex 21-electron polyhedron, a slightly
      distorted closo-Sn(9)Ni cluster with an additional interstitial Ni atom and
      overall C(4)(v)() point symmetry. The EPR spectrum showed a five-line pattern due
      to 4.8-G hyperfine interactions involving all nine tin atoms. The ESI-MS analysis
      showed weak signals for the potassium complex [K(2)Sn(9)Ni(2)(CO)](1-) and the
      ligand-free binary ions [K(2)Sn(9)Ni(2)](1)(-), [KSn(9)Ni(2)](1)(-), and
      [HSn(9)Ni(2)](1)(-).

PMID- 11971728
TI  - Electron-rich three-center bonding: role of s,p interactions across the p-block.
AB  - This paper analyzes the importance of s,p mixing-a necessary addition to the
      simplest Rundle-Pimentel picture-and periodic and group trends in electron-rich
      three-center bonding. Our analysis proceeds through a detailed quantum chemical
      study of the stability of electron-rich three-center bonding in triatomic 22
      valence electron anions. To provide interpretations, a perturbational molecular
      orbital (MO) analysis of s,p mixing is carried out. This analysis of the orbitals
      and the overlap populations is then tested by density functional calculations for
      a number of linear trihalides, trichalcogenides, and tripnictides. The most
      important effect of s,p mixing on the in-line bonding is in destabilization of
      the 3sigma(g) orbital and is determined by the overlap between the s orbital of
      the central atom and the p orbital of the terminal atom. Further destabilization
      arises from the repulsion of p(pi) lone pairs. Both of these antibonding effects
      increase with increasing negative charge of the system. The stability of
      isoelectronic X(3) systems thus decreases when moving from right to left in the
      periodic table. Interesting group trends are discerned; for instance, for the
      electron-rich tripnictides, the ability to accommodate a hypervalent electron
      count is the largest in the middle rather at the end of the group. Particularly
      strong s,p mixing can reverse the bonding/antibonding character of MOs: thus MO
      2sigma(u) that is responsible for bonding for trihalides and trichalcogenides is
      actually antibonding in N(3)(7)(-).

PMID- 11971729
TI  - Photocurrent generation in multilayer organic-inorganic thin films with cascade
      energy architectures.
AB  - Zirconium organobisphosphonate multilayer thin films of viologen derivatives were
      grown on copper dithiolate multilayers of 5,15-di(p-thiolphenyl)-10,20-di(p
      tolyl)porphyrin (POR) and 5,15-di(p-thiolphenyl)-10,20-di(p-tolyl)porphyrinzinc
      (ZOR) on a variety of substrates (e.g. Au, SiO(2)), using solution depositions
      methods. The multilayer structures were studied by atomic force microscopy, UV
      vis spectroscopy, and ellipsometry. In the case of copper dithiolate thin films,
      layer-by-layer lamellar growth with low surface roughness resulted, while higher
      surface roughness was observed in the growth of Zr viologen bisphosphonate films.
      Gold electrodes modified with zirconium bisphosphonate multilayers of viologen on
      top of copper dithiolate multilayers of porphyrin derivatives (ZOR or POR) were
      photoelectroactive and produced efficient and stable photocurrents using visible
      light. By arranging the zinc-porphyrin (ZOR) and the free base porphyrin (POR)
      donors in an energetically favorable fashion, according to their redox potentials
      and optical energy gaps, the photoinduced charge separation was improved, and
      higher photocurrent quantum yields ( approximately 4%) and fill factor (
      approximately 50%) of the photoelectrode were achieved.

PMID- 11971731
TI  - Bcc and Fcc transition metals and alloys: a central role for the Jahn-Teller
      effect in explaining their ideal and distorted structures.
AB  - Transition metal elements, alloys, and intermetallic compounds often adopt the
      body centered cubic (bcc) and face centered cubic (fcc) structures. By comparing
      quantitative density functional with qualitative tight-binding calculations, we
      analyze the electronic factors which make the bcc and fcc structures
      energetically favorable. To do so, we develop a tight-binding function,
      DeltaE(star), a function that measures the energetic effects of transferring
      electrons within wave vector stars. This function allows one to connect
      distortions in solids to the Jahn-Teller effect in molecules and to provide an
      orbital perspective on structure determining deformations in alloys. We
      illustrate its use by considering first a two-dimensional square net. We then
      turn to three-dimensional fcc and bcc structures, and distortions of these. Using
      DeltaE(star), we rationalize the differences in energy of these structures. We
      are able to deduce which orbitals are responsible for instabilities in seven to
      nine valence electron per atom (e(-)/a) bcc systems and five and six e(-)/a fcc
      structures. Finally we demonstrate that these results account for the bcc and fcc
      type structures found in both the elements and binary intermetallic compounds of
      group 4 through 9 transition metal atoms. The outline of a theory of metal
      structure deformations based on loss of point group operation rather than
      translational symmetry is presented.

PMID- 11971730
TI  - Conformational selection of glycomimetics at enzyme catalytic sites: experimental
      demonstration of the binding of distinct high-energy distorted conformations of C
      , S-, and O-glycosides by E. Coli beta-galactosidases.
AB  - We show that the conformational features of the molecular complexes of E. coli
      beta-galactosidase and O-glycosides may differ from those formed with closely
      related compounds in their chemical nature, such as C- and S-glycosyl analogues.
      In the particular case presented here, NMR and ab initio quantum mechanical
      results show that the 3D-shapes of the ligand/inhibitor within the enzyme binding
      site depend on the chemical nature of the compounds. In fact, they depend on the
      relative size of the stereoelectronic barriers for chair deformation or for
      rotation around Phi glycosidic linkage.

PMID- 11971732
TI  - Molecular rulers: new families of molecules for measuring interfacial widths.
AB  - Homologous series of solvatochromic neutral alcohols and ionic sulfates are
      synthesized and characterized. Each surfactant series consists of hydrophobic, p
      nitroanisole-based chromophores attached to polar or ionic headgroups by n-alkyl
      spacers. UV absorption measurements show that the optical properties of
      surfactant chromophores closely track those of the parent chromophore.
      Interfacial tension measurements are used to calculate surface excess
      concentrations of ionic surfactants adsorbed to an aqueous-cyclohexane interface.
      With a hydrophobic chromophore, a hydrophilic headgroup, and a variable-length,
      alkyl spacer, these surfactants have the potential to function as molecular
      rulers: probes of molecular-scale variation in solvation forces across condensed
      phase interfaces. Changing the separation between the hydrophobic, solvatochromic
      probe and the hydrophilic headgroup should enable different members of a
      homologous series to span different interfacial widths, thus exposing the
      chromophore to different chemical environments. This idea is explored by using
      surface-specific, nonlinear optical spectroscopy. Resonant second harmonic
      spectra of p-nitroanisole and the surfactant product 4a adsorbed to an aqueous
      cyclohexane interface show the surfactant spectrum blue-shifted 9 nm relative to
      the spectrum of adsorbed p-nitroanisole. On the basis of chromophore
      solvatochromism, these results are consistent with a less polar environment
      surrounding the surfactant chromophore. Significant differences in interfacial
      solvation resulting from a approximately 5 A separation between the surfactant
      headgroup and chromophore support recently proposed models of molecularly sharp,
      microscopically flat aqueous-alkane interfaces.

PMID- 11971733
TI  - Cation-pi interactions: an energy decomposition analysis and its implication in
      delta-opioid receptor-ligand binding.
AB  - The nature and strength of the cation-pi interaction in protein-ligand binding
      are modeled by considering a series of nonbonded complexes involving N
      substituted piperidines and substituted monocylic aromatics that mimic the delta
      opioid receptor-ligand binding. High-level ab initio quantum mechanical
      calculations confirm the importance of such cation-pi interactions, whose
      intermolecular interaction energy ranges from -6 to -12 kcal/mol. A better
      understanding of the electrostatics, polarization, and other intermolecular
      interactions is obtained by appropriately decomposing the total interaction
      energy into their individual components. The energy decomposition analysis is
      also useful for parametrizing existing molecular mechanics force fields that
      could then account for energetic contributions arising out of cation-pi
      interactions in biomolecules. The present results further provide a framework for
      interpreting experimental results from point mutation reported for the delta
      opioid receptor.

PMID- 11971734
TI  - Bending of DNA by asymmetric charge neutralization: all-atom energy simulations.
AB  - DNA dodecamers of the alternating d(CG).d(CG) sequence with six phosphate groups
      either charge-neutralized or substituted by neutral methylphosphonates across the
      major or minor groove have been subjected to energy minimization to determine the
      conformational effect of the asymmetric elimination of phosphate charge. We
      report bending angles, directions of bending, and detailed structural
      characteristics such as groove widths and local base-pair parameters. Our
      principal results are that charge neutralization on one face of the DNA induces
      significant bending toward the neutralized face, in agreement with theoretical
      predictions on a simplified model and experimental data on a similar base-pair
      sequence, and that the DNA conformation averaged over all stereospecific
      methylphosphonate substitutions is nearly the same as the conformation produced
      by charge neutralization of the phosphates. Individual isomers, however, cover a
      wide range of structures, with the magnitude and direction of overall bending
      sensitive to the precise stereochemical pattern of neutralization. Our simulation
      does not explicitly contain counterions, and the results therefore suggest that
      counterions can influence DNA structure by neutralizing the phosphate charge.
      These data provide new hints into the molecular mechanisms which underlie the
      deformations of DNA structure induced by the binding of positively charged
      proteins and other tightly associated cationic species.

PMID- 11971735
TI  - Theoretical investigation of large kinetic isotope effects for proton-coupled
      electron transfer in ruthenium polypyridyl complexes.
AB  - A theoretical investigation of proton-coupled electron transfer in ruthenium
      polypyridyl complexes is presented. The three reactions studied are as follows:
      (1) the comproportionation reaction of [(bpy)(2)(py)Ru(IV)O](2+) and
      [(bpy)(2)(py)Ru(II)OH(2)](2+) to produce [(bpy)(2)(py)Ru(III)OH](2+); (2) the
      comproportionation reaction of [(tpy)(bpy)Ru(IV)O](2+) and
      [(tpy)(bpy)Ru(II)OH(2)](2+) to produce [(tpy)(bpy)Ru(III)OH](2+); and (3) the
      cross reaction of [(tpy)(bpy)Ru(III)OH](2+) and [(bpy)(2)(py)Ru(II)OH(2)](2+) to
      produce [(tpy)(bpy)Ru(II)OH(2)](2+) and [(bpy)(2)(py)Ru(III)OH](2+). This
      investigation is motivated by experimental measurements of rates and kinetic
      isotope effects for these systems (Binstead, R. A.; Meyer, T. J. J. Am. Chem.
      Soc. 1987, 109, 3287. Farrer, B. T.; Thorp, H. H. Inorg. Chem. 1999, 38, 2497.).
      These experiments indicate that the second reaction is nearly one order of
      magnitude faster than the first reaction, and the third reaction is in the
      intermediate regime. The experimentally measured kinetic isotope effects for
      these three reactions are 16.1, 11.4, and 5.8, respectively. The theoretical
      calculations elucidate the physical basis for the experimentally observed trends
      in rates and kinetic isotope effects, as well as for the unusually high magnitude
      of the kinetic isotope effects. In this empirical model, the proton donor
      acceptor distance is predicted to be largest for the first reaction and smallest
      for the third reaction. This prediction is consistent with the degree of steric
      crowding near the oxygen proton acceptor for the three reactions. The second
      reaction is faster than the first reaction since a smaller proton donor-acceptor
      distance leads to a larger overlap between the reactant and product proton
      vibrational wave functions. The intermediate rate of the third reaction is
      determined by a balance among several competing factors. The observed trend in
      the kinetic isotope effects arises from the higher ratio of the hydrogen to
      deuterium vibrational wave function overlap for larger proton donor-acceptor
      distances. Thus, the kinetic isotope effect increases for larger proton donor
      acceptor distances. The unusually high magnitude of the kinetic isotope effects
      is due in part to the close proximity of the proton transfer interface to the
      electron donor and acceptor. This proximity results in strong electrostatic
      interactions that lead to a relatively small overlap between the reactant and
      product vibrational wave functions.

PMID- 11971737
TI  - Formation of transient intermediates in low-temperature photosensitized oxidation
      of an 8-(13)C-guanosine derivative.
AB  - An 8-(13)C-labeled guanosine derivative, 2',3',5'-O-tert-butyldimethylsilyl-N
      tert-butyldimethylsilyl-8-(13)C-guanosine, was synthesized and its
      photosensitized oxidation with singlet oxygen carried out below -100 degrees C.
      Two transient intermediates that decompose directly to the final major product 5
      and CO(2) were detected by (13)C NMR between -100 and -43 degrees C. The two
      intermediates are carbamic acids based on (13)C NMR and 2D NMR (HMQC, HMBC)
      spectra and the formation of final product 5 and of 8-CO(2). No endoperoxide
      intermediate could be detected by low-temperature NMR spectroscopy even at -100
      degrees C. A reaction mechanism is proposed involving initial [4 + 2]
      cycloaddition of singlet oxygen to the imidazole ring to form an unstable
      endoperoxide, subsequent rearrangement of the endoperoxide to a dioxirane, and
      decomposition of the dioxirane to the two observed intermediates. Both oxygen
      atoms of CO(2) are derived from a single oxygen molecule, which strongly supports
      a dioxirane structure for the precursor of the two observed intermediates. The
      distribution of products estimated by (13)C NMR accounts for all the (13)C
      containing products in the reaction mixture.

PMID- 11971738
TI  - Design and synthesis of chemiluminescent probes for the detection of
      cholinesterase activity.
AB  - Acetylcholinesterase is one of the most widely used and studied enzymes. Not only
      does this enzyme regulate neurotransmission (and thus play a key role in
      neurodegenerative processes) but it is also a prime target for pest control
      agents and warfare agents. Above all, due to its particularly high turnover rate,
      acetylcholinesterase is among the most efficient reporter enzymes yet described
      (for use as enzymatic tracer in immunoassays, for instance). However, its
      activity is detected through a colorimetric reagent, the Ellman reagent, which
      displays low detection limits and is often subject to background perturbations.
      In the course of our search for a more sensitive detection assay, we describe
      here a first-generation 1,2-dioxetane chemiluminescent probe, based on chemically
      induced electron exchange luminescence, which has an approximately 10 times lower
      detection limit than the Ellman colorimetric assay (2.5 x 10(-19) mol for
      Electrophorus electricus AChE in its tetrameric form).

PMID- 11971739
TI  - [Ni(0)L]-catalyzed cyclodimerization of 1,3-butadiene: a comprehensive density
      functional investigation based on the generic [(C(4)H(6))(2)Ni(0)PH(3)] catalyst.
AB  - We present a comprehensive theoretical investigation of the mechanism for
      cyclodimerization of butadiene by the generic [bis(butadiene)Ni(0)PH(3)] catalyst
      employing a gradient-corrected DFT method. We have explored all critical
      elementary steps of the whole catalytic cycle, namely, oxidative coupling of two
      butadienes, reductive elimination under ring closure, and allylic isomerization.
      Oxidative coupling of two butadienes in the [bis(butadiene)Ni(0)L] complex and
      reductive elimination in the [(bis(eta(3))-octadienediyl)Ni(II)L] species take
      place under different stereocontrol, which makes isomerization indispensable.
      Commencing from a preestablished equilibrium between several configurations of
      the [(octadienediyl)Ni(II)L] complex, the major cyclodimer products, namely, VCH,
      cis-1,2-DVCB, and cis,cis-COD, are formed along competing reaction paths via
      reductive elimination, which is found to be the overall rate-determining step.
      Careful exploration of different possible conceivable routes revealed that
      bis(eta(1)) species are not involved as critical intermediates either in
      reductive elimination or in isomerization along the most feasible pathway. The
      regulation of the selectivity of the cyclodimer formation based on both
      thermodynamic and kinetic considerations is outlined.

PMID- 11971736
TI  - Time-resolved resonance Raman analysis of chromophore structural changes in the
      formation and decay of rhodopsin's BSI intermediate.
AB  - Time-resolved resonance Raman microchip flow experiments are performed to obtain
      the vibrational spectrum of the chromophore in rhodopsin's BSI intermediate and
      to probe structural changes in the bathorhodopsin-to-BSI and BSI-to-lumirhodopsin
      transitions. Kinetic Raman spectra from 250 ns to 3 micros identify the key
      vibrational features of BSI. BSI exhibits relatively intense HOOP modes at 886
      and 945 cm(-1) that are assigned to C(14)H and C(11)H=C(12)H A(u) wags,
      respectively. This result suggests that in the bathorhodopsin-to-BSI transition
      the highly strained all-trans chromophore has relaxed in the C(10)-C(11)=C(12)
      C(13) region, but is still distorted near C(14). The low frequency of the 11,12
      A(u) HOOP mode in BSI compared with that of lumirhodopsin and metarhodopsin I
      indicates weaker coupling between the 11H and 12H wags due to residual distortion
      of the BSI chromophore near C(11)=C(12). The C=NH(+) stretching mode in BSI at
      1653 cm(-1) exhibits a normal deuteriation induced downshift of 23 cm(-1),
      implying that there is no significant structural rearrangement of the Schiff base
      counterion region in the transition of bathorhodopsin to BSI. However, a dramatic
      Schiff base environment change occurs in the BSI-to-lumirhodopsin transition,
      because the 1638 cm(-1) C=NH(+) stretching mode in lumirhodopsin is unusually low
      and shifts only 7 cm(-1) in D(2)O, suggesting that it has essentially no H
      bonding acceptor. With these data we can for the first time compare and discuss
      the room temperature resonance Raman vibrational structure of all the key
      intermediates in visual excitation.

PMID- 11971740
TI  - Periodic trends in indirect nuclear spin-spin coupling tensors: relativistic
      density functional calculations for interhalogen diatomics.
AB  - There have been significant advances in the calculation and interpretation of
      indirect nuclear spin-spin coupling (J) tensors during the past few years;
      however, much work remains to be done, especially for molecules containing heavy
      atoms where relativistic effects may play an important role. Many J tensors
      cannot be explained based solely on a nonrelativistic Fermi-contact mechanism. In
      the present work, the relativistic zeroth-order regular approximation density
      functional (ZORA-DFT) implementation for the calculation of J has been applied to
      the complete series of homonuclear and heteronuclear diatomic halogen molecules:
      F(2), Cl(2), Br(2), I(2), At(2), ClF, BrF, IF, ClBr, ClI, and BrI. For all of
      these compounds, the reduced isotropic coupling constant (K(iso)) is positive and
      the reduced anisotropic coupling constant (DeltaK) is negative. With the
      exception of molecular fluorine, the magnitudes of K(iso) and DeltaK are shown to
      increase linearly with the product of the atomic numbers of the coupled nuclei.
      ZORA-DFT calculations of J for F(2) and ClF are in excellent agreement with the
      results obtained from multiconfigurational self-consistent-field calculations.
      The relative importance of the various coupling mechanisms is approximately
      constant for all of the compounds, with the paramagnetic spin-orbit term being
      the dominant contributor to K(iso), at approximately 70-80%. Available
      experimental stimulated resonant Raman spectroscopy data are exploited to extract
      the complete J((127)I,(127)I) tensor for iodine in two rotational states. The
      dependence of K(iso) and DeltaK on bond length and rovibrational state is
      investigated by using calculated results in combination with available
      experimental data. In addition to providing new insights into periodic trends for
      J coupling tensors, this work further demonstrates the utility of the ZORA-DFT
      method and emphasizes the necessity of spin-orbit relativistic corrections for J
      calculations involving heavy nuclei.

PMID- 11971741
TI  - Conformational characterization of lanthanide(III)-DOTA complexes by ab initio
      investigation in vacuo and in aqueous solution.
AB  - The conformational behavior of four [Ln(DOTA)(H(2)O)](-) systems (Ln = La, Gd,
      Ho, and Lu) has been characterized by means of ab initio calculations performed
      in vacuo and in aqueous solution, the latter by using the polarizable continuum
      model (PCM). Calculated molecular geometries and conformational energies of the
      [Ln(DOTA)(H(2)O)](-) systems, and interconversion mechanisms, barriers, and (13)C
      NMR spectra of the [Lu(DOTA)](-) complex are compared with experimental values.
      For each system, geometry optimizations, performed in vacuo and in solution at
      the HF/3-21G level and using a 46+4f(n) core electron effective core potential
      (ECP) for lanthanides, provide two minima corresponding to a square antiprismatic
      (A) and an inverted antiprismatic (IA) coordination geometry. All the systems are
      nonacoordinated, with the exception of the IA isomer of the Lu complex that, from
      in solution calculations, is octacoordinated, in agreement with experimental
      data. On comparing the in vacuo relative free energies calculated at different
      theory levels it can be seen that the nonacoordinated species dominates at the
      beginning of the lanthanide series while the octacoordinated one does so at the
      end. Furthermore, on passing along the series the IA isomer becomes less and less
      favored with respect to A and for the Lu complex a stabilization of the IAisomer
      is observed in solution (but not in vacuo), in agreement with the experimental
      data. Investigation of the A<-->IA isomerization process in the [Lu(DOTA)](-)
      system provides two different interconversion mechanisms: a single-step process,
      involving the simultaneous rotation of the acetate arms, and a multistep path,
      involving the inversion of the cyclen cycle configuration. While in vacuo the
      energy barrier for the acetate arm rotation is higher than that involved in the
      ring inversion (23.1 and 13.1 kcal mol(-)(1) at the B3LYP/6-311G level,
      respectively), in solution the two mechanisms present comparable barriers (14.7
      and 13.5 kcal mol(-)(1)), in fairly good agreement with the experimental values.
      The NMR shielding constants for the two isomers of the [Lu(DOTA)](-) complex have
      been calculated by means of the ab initio GIAO and CSGT methods, and using a 46
      core-electron ECP for Lu. The calculated (13)C NMR chemical shifts are in close
      agreement with the experimental values (rms 3.3 ppm, at the HF/6-311G level) and
      confirm the structural assignment of the two isomers based on experimental NMR
      spectra in solution. The results demonstrate that our computational approach is
      able to predict several physicochemical properties of lanthanide complexes,
      allowing a better characterization of this class of compounds for their
      application as contrast agents in medical magnetic resonance imaging (MRI).

PMID- 11971742
TI  - Gas-phase stability of derivatives of the closo-hexaborate dianion B(6)H(6)(2-).
AB  - B(6)H(6)(2-) does not represent a stable gas-phase dianion, but emits
      spontaneously one of its excess electrons in the gas phase. In this work we
      address the question whether small stable gas-phase dianions can be constructed
      from the parent B(6)H(6)(2-) dianion by substitution of the hydrogens with
      appropriate ligands. Various hexa-, tetra-, and disubstituted derivatives
      B(6)L(6)(2-), B(6)H(2)L(4)(2-), and B(6)H(4)L(2)(2-) (L = F, Cl, CN, NC, or BO)
      are investigated with ab initio methods in detail. Four stable hexasubstituted
      B(6)L(6)(2-) (L = Cl, CN, NC, or BO) and three stable B(6)H(2)L(4)(2-) (L = CN,
      NC, or BO) gas-phase dianions could be identified and predicted to be observable
      in the gas phase. The trends in the electron-detachment energies depending on
      various ligands are discussed and understood in the underlying electrostatic
      pattern and the electronegativities of the involved elements.

PMID- 11971743
TI  - Solid-state light-emitting devices based on the tris-chelated ruthenium(II)
      complex. 4. High-efficiency light-emitting devices based on derivatives of the
      tris(2,2'-bipyridyl) ruthenium(II) complex.
AB  - Light-emitting devices from the tris(2,2'-bipyridyl)ruthenium(II) complex
      [Ru(bpy)(3)(2+)] and new derivatives thereof were prepared. Due to the
      electrochemical nature of the device operation, single-layer devices in an ITO/
      Ru(bpy)(3)(2+) complex + PMMA/Ag sandwich configuration achieved very high
      external quantum efficiencies. The derivatives of the Ru(bpy)(3)(2+) complex were
      designed and synthesized to inhibit self-quenching of the excited state by adding
      different alkyl substituents on the bipyridyl ligands. As a result, devices that
      contain these new Ru(bpy)(3)(2+) complexes show a higher photoluminescence and
      electroluminescence efficiency than devices made from the unmodified
      Ru(bpy)(3)(2+) complex. External quantum efficiencies up to 5.5% at brightnesses
      in the range of 10-50 cd/m(2) are reported. In addition, the response time of
      such devices (which is a result of the electrochemical operation) has been
      shortened dramatically. An "instantaneous" light emission is achieved for devices
      that employ smaller counterions such as BF(4)(-) to increase the ionic
      conductivity. Such a device shows a response time of less than 1 s to emit 10-20
      cd/m(2) after the operating voltage of 2.4 V has been applied.

PMID- 11971744
TI  - Modified phthalocyanines for efficient near-IR sensitization of nanostructured
      TiO(2) electrode.
AB  - A zinc phthalocyanine with tyrosine substituents (ZnPcTyr), modified for
      efficient far-red/near-IR performance in dye-sensitized nanostructured TiO(2)
      solar cells, and its reference, glycine-substituted zinc phthalocyanine
      (ZnPcGly), were synthesized and characterized. The compounds were studied
      spectroscopically, electrochemically, and photoelectrochemically. Incorporating
      tyrosine groups into phthalocyanine makes the dye ethanol-soluble and reduces
      surface aggregation as a result of steric effects. The performance of a solar
      cell based on ZnPcTyr is much better than that based on ZnPcGly. Addition of
      3alpha,7alpha-dihydroxy-5beta-cholic acid (cheno) and 4-tert-butylpyridine (TBP)
      to the dye solution when preparing a dye-sensitized TiO(2) electrode diminishes
      significantly the surface aggregation and, therefore, improves the performance of
      solar cells based on these phthalocyanines. The highest monochromatic incident
      photo-to-current conversion efficiency (IPCE) of approximately 24% at 690 nm and
      an overall conversion efficiency (eta) of 0.54% were achieved for a cell based on
      a ZnPcTyr-sensitized TiO(2) electrode. Addition of TBP in the electrolyte
      decreases the IPCE and eta considerably, although it increases the open-circuit
      photovoltage. Time-resolved transient absorption measurements of interfacial
      electron-transfer kinetics in a ZnPcTyr-sensitized nanostructured TiO(2) thin
      film show that electron injection from the excited state of the dye into the
      conduction band of TiO(2) is completed in approximately 500 fs and that more than
      half of the injected electrons recombines with the oxidized dye molecules in
      approximately 300 ps. In addition to surface aggregation, the very fast electron
      recombination is most likely responsible for the low performance of the solar
      cell based on ZnPcTyr.

PMID- 11971745
TI  - Profile of dyslipidemia in Psammomys obesus, an animal model of the metabolic
      syndrome.
AB  - OBJECTIVE: To investigate lipid profiles in Psammomys obesus and relationships
      between lipid profile and other components of the Metabolic Syndrome. METHODS: A
      total number of 49 adults with a wide range of body weight and glucose tolerance
      were studied in a cross-sectional analysis. Plasma cholesterol distribution
      profiles were measured by size exclusion lipid chromatography. Blood glucose was
      measured using an enzymatic glucose analyser, and plasma insulin was determined
      by radioimmunoassay. RESULTS: Obese diabetic Psammomys obesus had elevated plasma
      cholesterol (P=0.003) and triglyceride levels (p>0.001) compared to their lean
      littermates. The hypercholesterolemia was mainly due to increased circulating
      levels of VLDL-cholesterol (P=0.003) and LDL-cholesterol (P=0.003) in these
      animals. Multiple linear regression analyses revealed that body weight was
      independently associated with plasma cholesterol (P=0.011) and LDL concentration
      (P=0.009), while plasma insulin was associated with VLDL-cholesterol
      concentration (P=0.005). All of the variables measured exhibited continuous
      distributions across a wide range of phenotypes, from a normal rodent lipid
      profile to profound dyslipidemia. CONCLUSIONS: These data suggest that the
      dyslipidemia in obese, diabetic Psammomys obesus is closely associated with other
      components of the Metabolic Syndrome, including obesity and insulin resistance.

PMID- 11971747
TI  - Potential role of nitric oxide in endothelin-1 provoked inhibition of
      progesterone secretion by isolated ovarian granulosa cells.
AB  - OBJECTIVE: Nitric oxide (NO) is involved in different cell functions including
      ovarian steroid production. Endothelin-1 (ET-1) was found to regulate the
      steroidogenesis in ovarian granulosa cells (GC). The present study was designed
      to receive more information about the mechanism of action of NO in the process of
      ET-1 induced progesterone (P) inhibition, using nicotine amide dinucleotide
      phosphate-diaphorase (NADPH-d) histochemistry as a cofactor of oxidoreductase
      enzymes (e. g. nitric oxide). METHODS: Granulosa cells were isolated from ovaries
      of: 1. young women with natural cycle or after in vitro fertilization (IVF), 2.
      premenopausal women. The obtained cells were cultured with endothelin-1 and the
      concentration of progesterone in conditioned media was determined by RIA. For the
      estimation of NADPH-d the histochemical reaction was used. RESULTS: The
      suppressive effect of ET-1 on P production in granulosa cells was more pronounced
      in young women with natural cycles, slightly weaker after IVF and the most
      ineffective in premenopausal patients. The number of NADPH-d positive GCs was
      higher in young non-hormonally stimulated women, slightly lower after IVF and
      small in premenopausal ones. CONCLUSIONS: The results indicate the possible role
      of NADPH-d or NOS in the mechanism of ET-1 provoked P suppression.

PMID- 11971746
TI  - Dynamic pattern of IGF-I and chosen biochemical markers of bone metabolism in a
      rat model of postmenopausal osteoporosis.
AB  - OBJECTIVE: To assess the relationship between the dynamic pattern of IGF-I levels
      and chosen biochemical markers of bone metabolism in ovariectomized rats - a
      model of postmenopausal osteoporosis. METHODS: Six-month-old rats were randomized
      to sham operation (control group) or ovariectomy. Serum levels of insulin-like
      growth factor (IGF-I) and chosen biochemical markers of bone metabolism (alkaline
      phosphatase - ALP, carboxyterminal propeptide of type I procollagen - PICP, cross
      linked carboxyterminal telopeptide of type I collagen - ICTP in serum as well as
      urinary excretion of hydroxyproline - HYP and total calcium - Ca) were measured
      before (group 0) and 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 and 28 weeks after the
      operation. RESULTS: In a model of experimental osteoporosis induced by
      ovariectomy in female rats a distinct tendency to decrease the IGF-I
      concentrations was shown. Differences were significant in relation to the control
      group in a period from 2 to 28 weeks after operation. Ovariectomy stimulated the
      values of studied markers of bone metabolism; it was more intensified in regard
      to resorption markers. Significant ICTP and HYP concentrations' changes, in
      relation to the control group, were shown in the some period and total calcium -
      from 2 to 16 weeks after ovariectomy. However, the values of studied markers of
      bone formation were generally changing to a slight degree. Significant
      differences of ALP activity, in relation to the control group, were observed only
      at 8 and 20 weeks, while those of PICP concentrations were found at in 4, 8 and
      12 weeks after the operation. The alterations in the levels of IGF-I correlated
      significantly and negatively with the changes in ALP activity as well as in PICP,
      ICTP, HYP and Ca concentrations both in ovariectomized and control rats. This
      relation was more expressed in the ovariectomized group. CONCLUSIONS: Our
      findings suggest that secondary changes in IGF-I concentration, due to the
      deficiency of sex hormones, results in altered bone metabolism in ovariectomized
      rats.

PMID- 11971748
TI  - Detection of oxytocin mRNA in hypertonic saline Fos-activated PVN neurons:
      comparison of chromogens in dual immunocytochemical and in situ hybridization
      procedure.
AB  - OBJECTIVE: The aim of the present experiments was to elucidate: 1. the stability
      and usefulness of a 3,3 -diaminobenzidine tetrahydrochloride (DAB) chromogen
      intensified with nickel and cobalt (DAB-Ni-Co) in the dual immunocytochemical and
      in situ hybridization procedure using Fos-protein antibody and oxytocin mRNA (OXY
      mRNA) radiolabeled probe; 2. the susceptibility of the free floating and mounted
      cryostat sections, freshly prepared or stored for 24 month at -20 degrees C.
      METHODS: The dual staining procedure was tested on neurons of the hypothalamic
      paraventricular nucleus (PVN) activated by an intraperitoneal injection of
      hypertonic saline (HS, 1.5 M, 5 ml, 60 min). Two dual labeling procedures were
      compared: 1/ Fos-immunostaining with DAB alone and combined with OXY mRNA in situ
      hybridization and 2/ Fos-immunostaining with DAB-Ni-Co and combined with OXY mRNA
      in situ hybridization. In both experiments free floating and mounted cryostat
      sections, freshly prepared or stored for 24 month at -20 degrees C, were tested.
      RESULTS: HS strongly stimulated both the parvicellular and magnocellular
      population of PVN neurons followed by an extensive Fos-immunolabeling in many
      cell nuclei. The first staining sequence with Fos-DAB labeling resulted in a good
      staining quality on both the fresh and for 24 month stored mounted sections.
      Although the free floating sections during the in situ procedure showed the same
      staining properties as the mounted ones, with respect to their increased
      fragility on the end of the hybridization procedure, they were difficult to mount
      and stretch on poly-L-lysine coated slides. On the other hand, Fos-immunolabeling
      with DAB-Ni-Co exhibited improved staining density of the single DAB chromogen in
      the first staining sequence of the dual staining procedure. However, DAB-Ni-Co
      mixture showed up as an unstable chromogen complex, which after completing the in
      situ hybridization process completely disappeared from each type of section.
      CONCLUSIONS: The results of the present dual immunocytochemical-in situ
      hybridization staining utilizing Fos-antibody and OXY mRNA oligoprobe indicate
      that this procedure is applicable on free floating as well as mounted cryostat
      sections, freshly prepared or stored for 24 month at -20 degrees C. However, the
      dual procedure is only successful when the immunoproduct in the first sequence is
      visualized with an unintensified DAB and not with combined DAB-Ni-Co chromogen
      and when the histological sections in the second sequence are not processed as
      free floating but are attached to a poly-L-lysine coated microscopic glasses.

PMID- 11971749
TI  - Transglutamines and endocrine system (minireview).
AB  - Transglutaminases catalyze the posttranslation modification of proteins by
      catalyzing Ca2+ dependent acyl-transfer reaction resulting in the formation of
      new g-amide bonds between g-carboxamide groups of peptide-bound glutamine
      residues and various primary amines. Such glutamine residue serves as acyl-donor
      and the most common acyl-acceptors are e-amino groups of peptide-bound lysine
      residues or primary amino groups of some naturally occurring polyamines, like
      putrescine or spermidine. The active site of cysteine reacts first with the g
      carboxamide group of glutamine residue to form the acyl-enzyme intermediate under
      the release of ammonia. In the second step, the complex reacts with a primary
      amine to form an isopeptide bond and liberate the reactivated enzyme. The
      presence of transglutaminases has been observed in various endocrine glands such
      as human pituitary, which was investigated by immunohistochemical methods using
      specific antibodies. A significant increase in the expression and activity of
      tissue transglutaminase was observed during involution of thymus. In the genital
      tract of the male rat two different forms of the enzyme transglutaminase could be
      identified and characterized. the presence of p53 and tissues transglutaminase
      gene expressions in human normal and pathologic adrenal tissues. The Ca2+
      responsive enzyme transglutaminase, which catalyzes the cross-bridging of
      proteins, was found in pancreatic islet cells.

PMID- 11971750
TI  - Hormone nuclear receptors and their ligands: role in programmed cell death
      (review).
AB  - Programmed cell death (PCD) represents a highly efficient and very sophisticated
      system for removing cells from the surrounding environment. As deadly as it may
      be, PCD is essential for elimination of aberrant cells and the survival of the
      living organism as a whole. Therefore, PCD is meticulously controlled, and among
      major regulatory actors belong small lipophilic hormones acting as ligands of the
      members of a nuclear receptor superfamily. In general, these hormones which
      include steroids, thyroids, retinoids, vitamin D3 derivatives, serve a critical
      role in the maintenance of homeostasis. For example, steroids regulate
      metabolism, reproduction, and development in animals that are as different as
      insects and humans. During animal development, steroids trigger distinct
      responses including cell differentiation and programmed cell death. Thus,
      hormones have been linked to numerous human health problems, and defects in
      hormone triggered programmed cell death may result e.g. in the survival of tumor
      cells or degenerative disorders. In vertebrate and invertebrate organisms where
      steroids including androgens, estrogens, progesterone, glucocorticoids and
      ecdysteroids regulate cell death, intensive study of this processes has resulted
      in a wealth of new information regarding how small lipophilic hormones contribute
      to cell demise within an organism. There is a great knowledge on the execution
      phase of apoptosis, the most frequent form of programmed cell death, and on the
      variety of its inducers. Even though we will review also recent advances on the
      topics various small ligands in the role of inducers, nevertheless we want to
      highlight the mechanisms that links action of hormones to the activation of
      apoptotic execution, the complex of processes, which are poorly understood so
      far.

PMID- 11971751
TI  - Replacing animal experimentation: not a question of if, but when, and by what
      route?

PMID- 11971752
TI  - Two in vitro models for gas-phase exposure to volatile compounds.
AB  - Two experimental models suitable for the screening of volatile compounds were set
      up. The first consisted of a glass-chamber slide with eight wells, one carrying
      the test compound, and the others carrying cells in monolayers. In the second
      model, the cells were cultured in a glass Petri dish, and the test compound was
      poured onto a filter lying on a glass cover-slip, supported by a metal ring. Four
      plant volatiles [carvacrol, S-(+)- carvone, thymol and decanal] and one essential
      oil (caraway oil) were chosen as test compounds. The toxicity rankings obtained
      with the two models were compared with that obtained in a previous study
      performed with the same compounds under conventional culture conditions.
      Differences in the toxicity ranking were observed between the conventional
      culture conditions and the gas-phase models, confirming the importance of correct
      exposure conditions for the evaluation of toxicity. Both models have advantages
      that make them suitable as a preliminary step in the toxicity screening of
      volatile compounds, or for use in a test battery when combined with conventional
      approaches.

PMID- 11971753
TI  - The ECVAM international validation study on in vitro embryotoxicity tests:
      results of the definitive phase and evaluation of prediction models. European
      Centre for the Validation of Alternative Methods.
AB  - From 1996 to 2000, ZEBET (Centre for Documentation and Evaluation of Alternative
      Methods to Animal Experiments at the BgVV, Berlin, Germany) coordinated the
      European Centre for the Validation of Alternative Methods (ECVAM) prevalidation
      and validation study on three embryotoxicity tests: a) a test employing embryonic
      stem cell lines (EST); b) the micromass (MM) test; and c) the postimplantation
      rat whole-embryo culture assay (WEC test). The main objectives of the study were
      to assess the performance of these three in vitro tests in discriminating between
      non- embryotoxic, weakly embryotoxic and strongly embryotoxic compounds. Phase I
      of the study (1997) was designed as a prevalidation phase, for test protocol
      optimisation, and for the establishment of a comprehensive database of in vivo
      and in vitro data on embryotoxic compounds. Phase II (1998-2000) involved a
      formal validation trial, conducted under blind conditions on 20 test compounds
      selected from the database, which were coded and distributed to the participating
      laboratories. In the preliminary phase of the validation study, six chemicals out
      of the 20, which showed embryotoxic potential, were tested. These results were
      used to define new biostatistically based prediction models (PMs) for the MM and
      WEC tests, and to evaluate those developed previously for the EST. As a next
      step, the PMs were evaluated by using the results for the remaining 14 chemicals
      of the definitive phase of the validation study. The three in vitro
      embryotoxicity tests proved to be applicable to testing a diverse group of
      chemicals with different embryotoxic potentials (non-embryotoxic, weakly
      embryotoxic, and strongly embryotoxic). The reproducibility of the three in vitro
      embryotoxicity tests were acceptable according to the acceptance criteria defined
      by the Management Team. The concordances between the embryotoxic potentials
      derived from the in vitro data and from the in vivo data were good for the EST
      and the WEC (PM2) test, and sufficient for the MM test and the WEC (PM1) tests
      according to the performance criteria defined by the Management Team before the
      formal validation study. When applying the PM of the EST to the in vitro data
      obtained in the definitive phase of the formal validation study, chemicals were
      classified correctly in 78% of the experiments. For the MM and the WEC tests, the
      PMs provided 70% and 80% (PM2) correct classifications, respectively. And, very
      importantly, an excellent predictivity (100%, except for PM1 of the WEC test,
      with 79%, considered as good) was obtained with strong embryotoxic chemicals in
      each of the three in vitro tests.

PMID- 11971754
TI  - Selection of test chemicals for the ECVAM international validation study on in
      vitro embryotoxicity tests. European Centre for the Validation of Alternative
      Methods.
AB  - The European Centre for the Validation of Alternative Methods (ECVAM) has
      sponsored a large international prevalidation and validation study of three
      embryotoxicity tests, involving embryonic stem cells, limb bud micromass
      cultures, and post-implantation whole-embryo cultures. The main objective of the
      study was to assess the performance of these in vitro tests in discriminating
      between non-embryotoxic, weakly embryotoxic and strongly embryotoxic compounds.
      An initial part of the study was to select 20 test substances for the formal
      validation trial, conducted under blind conditions. A database of in vivo and in
      vitro developmental toxicity test results was complied on 310 chemicals that had
      been used in previous validation studies, or suggested for such use, or that had
      good quality "segment II"-type in vivo data, or for which there were human data.
      From this database, a shortlist of about 30 candidates was constructed. Because
      the ECVAM study would not include metabolic activation, chemicals known to
      require activation for their developmental effects were excluded as candidates,
      although some known stable metabolites were included. Attempts were made: to
      include substances of diverse mechanism; to avoid overemphasis on
      pharmaceuticals; to avoid biologically inert substances as non-embryotoxicants;
      and to make the list different from those used previously. The candidates were of
      three categories: Class 3, strongly embryotoxic, was defined as developmentally
      toxic in all species tested, inducing multiple developmental effects, and with a
      high A/D ratio. Class 1, non-embryotoxic, was defined as not developmentally
      toxic at maternally toxic exposures, but which may show some minor embryo/fetal
      toxicity, which cannot be separated from maternal toxicity. Class 2, weakly
      embryotoxic, were chemicals of intermediate activity. From this candidate list,
      chemicals of known receptor (androgen, oestrogen, glucocorticoid, aryl
      hydrocarbon) mechanisms were excluded, on the basis that simple tests for such
      activity are already available. In addition, chemicals not freely available were
      excluded, and an emphasis on human data was applied. The final list of 20
      chemicals was: Class 3--6-aminonicotinamide, 5-bromo- 2'-deoxyuridine,
      hydroxyurea, methylmercury chloride, methotrexate, all-trans-retinoic acid; Class
      2--boric acid, dimethadione, lithium chloride, methoxyacetic acid, valproic acid
      (VPA), 2-propyl-4-pentynoic acid (4-yn-VPA), salicylic acid sodium salt; and
      Class 1--acrylamide, D-(+)-camphor, dimethyl phthalate, diphenhydramine
      hydrochloride, 2-ethyl-4- methylpentanoic acid (isobutyl-ethyl-VPA), Penicillin G
      sodium salt, saccharin sodium hydrate.

PMID- 11971755
TI  - Losartan decreases glomerular filtration rate in isolated perfused porcine
      slaughterhouse kidneys.
AB  - We investigated whether Losartan, an angiotensin II (Ang II) AT1 receptor
      antagonist, decreases renal vascular resistance (RVR) and increases glomerular
      filtration rate (GFR) in isolated perfused porcine slaughterhouse kidneys (11
      control experiments and 11 Losartan experiments with 7.5mg Losartan in the
      preservation solution and 100(g/minute Losartan infused during perfusion). With
      perfusion, plasma renin activity (PRA) increased markedly from 3 +/- 1 to 90 +/-
      17 ng Ang I/ml/h (control), and from 4 +/- 1 to 70 +/- 8 ng Ang I/ml/h
      (Losartan), plasma Ang II increased from 86 +/- 63 to 482 +/- 111 pg/ml
      (control), and from 73 +/- 42 to 410 +/- 91 pg/ml (Losartan). The GFR was
      decreased in Losartan experiments as compared with control experiments (5 +/- 1
      versus 10 +/- 2 ml/min/100g kidney wt; p < 0.05). The RVR was the same in both
      groups (0.2 +/- 0.01 mm Hg/100g kidney wt/min/ml). Tubular sodium reabsorption
      was decreased in Losartan experiments as compared with control experiments (0.7
      +/- 0.1 versus 1.4 +/- 0.3 mmol/min/100g kidney wt). Overall, Losartan
      accentuated pathophysiological signs of acute renal failure. Although other drugs
      have to be investigated, these results suggest that porcine slaughterhouse
      kidneys could be useful as a tool for research in areas such as transplantation
      and intensive-care medicine.

PMID- 11971756
TI  - In vitro setting of dose-effect relationships of 32 metal compounds in the
      Balb/3T3 cell line, as a basis for predicting their carcinogenic potential.
AB  - The results are reported of the second stage in a programme for a systematic in
      vitro study on the carcinogenic potential of metal compounds with Balb/3T3 clone
      A31-1-1 mouse fibroblasts. Nineteen metal compounds that exhibited a strong
      cytotoxic effect during a previous screening run with a 100 microM fixed dose
      were tested with a 72-hour exposure over a wide range of concentrations (from 0.1
      microM to 1000 microM), to produce dose-effect curves to permit extrapolation of
      the 50% inhibition concentration (IC50) values for each metal compound. This
      allows the establishment of a suitable range of doses for individual metal
      species, for use in the subsequent Balb/3T3 assay based on a two-stage concurrent
      cytotoxicity and morphological transformation protocol. Another 13 metal
      compounds were also tested, to determine whether the Balb/3T3 cell transformation
      assay is really a valuable in vitro model in relation to the problem of metal
      speciation. Of the metal compounds assayed, 26 showed a dose related cytotoxic
      response with calculated IC50 values ranging from 0.25 microM (CH3HgCl) to 140
      microM [(C5H5)2TiCl2], whereas six metal compounds, namely (NH4)6Mo7O24*4H2O,
      CH3AsO(OH)2, C2H6AsNaO2(3H2O, KBr, CrCl3*6H2O and (NH4)2[TiO(C2O4)2]*H2O,
      displayed no observable cytotoxicity or low cytotoxicity at all the doses tested.
      The determination of IC50 values permits a ranking of the cytotoxicity responses
      of metal compounds with the highest cytotoxicities. Dose-effect curves and IC50
      values of different chemical forms of individual metal compounds of As, Br, Cr,
      Hg, Ir, Pt, Te, Ti and V (cationic/anionic inorganic or organometallic species)
      showed clearly how the chemical nature of the metal strongly influences the toxic
      response. This confirms that the Balb/3T3 cell line is a valuable in vitro model
      with respect to the problem of metal speciation. This is a fundamental aspect to
      be considered when incorporating the results from in vitro cell transformation
      assays of the carcinogenic potential of metal compounds into regulatory testing
      schemes. In this context, the choice of test metal species for the development
      and validation of such assays cannot disregard the possibility that humans will
      be exposed to specific chemical forms of individual metal compounds (different
      oxidation states, and inorganic or organometallic natures) that can profoundly
      affect their toxicity.

PMID- 11971757
TI  - The use of fetal bovine serum: ethical or scientific problem?
AB  - Fetal bovine serum (FBS) is a common component of animal cell culture media. It
      is harvested from bovine fetuses taken from pregnant cows during slaughter. FBS
      is commonly harvested by means of a cardiac puncture without any form of
      anaesthesia. Fetuses are probably exposed to pain and/or discomfort, so the
      current practice of fetal blood harvesting is inhumane. Apart from moral
      concerns, several scientific and technical problems exist with regard to the use
      of FBS in cell culture. Efforts should be made to reduce the use of FBS or,
      preferably, to replace it with synthetic alternatives.

PMID- 11971758
TI  - Possibilities of replacing and reducing animal tests in the pharmacopoeias: an
      evaluation of unused methods and proposals for change.
AB  - The animal tests currently carried out according to the German and European
      pharmacopoeias are evaluated. The routine testing of biological medicines,
      excluding vaccines and pyrogen tests, is examined. The opportunities for
      replacing obligatory bioassays and safety tests are assessed, taking into account
      both pharmaceutical quality and animal welfare aspects. The aim is to encourage
      institutions, public authorities, and the pharmaceutical industry to investigate
      the importance and the necessity of the remaining tests. In addition, all parties
      should be encouraged to initiate integrated projects to develop, validate and
      establish alternative methods.

PMID- 11971759
TI  - Distinctive anti-influenza properties of recombinant collectin 43.
AB  - Collectins play important roles in innate defence against viral, fungal and
      bacterial pathogens. CL-43, a bovine serum collectin, which appears to have
      evolutionarily evolved from surfactant protein D (SP-D), shows unique structural
      and functional properties. In the present study, we describe the initial
      characterization of a recombinant CL-43 expressed in mammalian cells. Like
      natural CL-43, the recombinant is secreted as trimeric forms that show a
      preference for mannose and N-acetyl mannosamine. The natural and recombinant
      proteins have significantly higher haemagglutination-inhibiting activity against
      influenza A virus (IAV) than recombinant trimeric forms of SP-D. In contrast with
      the more highly multimerized forms of SP-D, namely conglutinin or mannose-binding
      lectin, CL-43 did not induce viral or bacterial aggregation and did not enhance
      IAV-induced neutrophil H(2)O(2) generation. Like SP-D, CL-43 also strongly
      enhanced neutrophil uptake of IAV. However, the mechanism of this enhanced
      internalization is different from that of SP-D in that it did not require viral
      aggregation. These studies establish that the trimeric structure of CL-43 is
      specified by its primary sequence and indicate that this naturally occurring
      trimeric collectin has unique antiviral activities. These findings could
      facilitate the development of recombinant collectins with novel antimicrobial
      properties.

PMID- 11971760
TI  - Gastrin-stimulated gastric epithelial cell invasion: the role and mechanism of
      increased matrix metalloproteinase 9 expression.
AB  - The gastric hormone gastrin regulates the organization of the gastric epithelium,
      but the cellular control mechanisms are yet unknown. Epithelial remodelling
      typically involves extracellular proteolysis mediated by the matrix
      metalloproteinases (MMPs). Since a gene-array analysis of the gastric cancer cell
      line AGS-G(R) suggested that gastrin increased MMP-9 expression, we examined the
      control of MMP-9 expression by gastrin. Gelatin zymography confirmed gastrin
      induction of MMP-9 in AGS-G(R) cells, but showed a small inhibition of MMP-2.
      Immunocytochemical studies showed that MMP-9 was localized to vesicles that
      appeared to traffic along the processes that were extended in response to
      gastrin. Gastrin stimulated the invasion of AGS-G(R) cells through artificial
      basement membrane, which was reduced by an inhibitor of MMP-2/-9. There was also
      an increase in MMP-9 in the stomach of patients with elevated plasma gastrin and
      multiple-endocrine neoplasia type 1 (MEN-1) syndrome, suggesting in vivo
      regulation of MMP-9 expression by gastrin. Finally, we showed that the expression
      of 1.9 kb of human MMP-9 gene promoter coupled with luciferase (MMP-9-luc) was
      increased 7.65+/-1.2-fold by gastrin, via a pathway which includes stimulation of
      protein kinase C, and activation of Raf and the mitogen-activated protein (MAP)
      kinase pathway. The tumour suppressor menin (which is mutated in MEN-1 syndrome)
      inhibited the expression of MMP-9-luc by gastrin. These results suggest that
      gastrin increases MMP-9 expression, which is associated with increased invasion,
      and this is a putative mechanism regulating remodelling of the gastric
      epithelium.

PMID- 11971761
TI  - Expression and regulation of the AMP-activated protein kinase-SNF1 (sucrose non
      fermenting 1) kinase complexes in yeast and mammalian cells: studies using
      chimaeric catalytic subunits.
AB  - Mammalian AMP-activated protein kinase (AMPK) and yeast SNF1 (sucrose non
      fermenting 1) kinase are members of a highly conserved protein kinase family that
      plays an important role in energy homoeostasis. AMPK and SNF1 kinase are
      heterotrimeric complexes consisting of a catalytic subunit and two regulatory
      subunits. We swapped the C-terminal regulatory domains of the catalytic subunits
      of AMPK (alpha) and SNF1 kinase (Snf1) and compared the expression and regulation
      of these chimaeric proteins with the native catalytic subunits in both mammalian
      and yeast cells. In mammalian cells, alpha1-Snf1 yielded a functional kinase
      complex following co-expression with the yeast regulatory subunits Sip2 and Snf4.
      Unlike native AMPK, the alpha 1-Snf1 complex was not activated by the stresses
      that deplete intracellular AMP. Significantly, hyperosmotic stress led to the
      marked activation of both the alpha 1-Snf1 complex and AMPK, without a detectable
      change in adenine nucleotide levels, indicating that an alternative, non-AMP
      dependent, pathway was responsible for activation. alpha1-Snf1 was able to
      restore growth of snf1 mutant yeast on raffinose and phosphorylated the
      transcriptional repressor protein Mig1. Co-expression of the AMPK trimeric
      complex in yeast yielded an activity, increased by low glucose, that was similar
      to native SNF1 kinase. Importantly, expression of AMPK restored growth of a snf1
      mutant on raffinose. Our results provide clues to the regulation of AMPK and SNF1
      kinase and demonstrate that, in mammalian cells, there are at least two pathways
      that can activate AMPK, namely one that involves an increase in the AMP/ATP ratio
      and one that is independent of this ratio. In yeast, the glucose signalling
      pathway is able to activate AMPK, suggesting that the mammalian and yeast kinase
      pathways are conserved.

PMID- 11971762
TI  - Homo- and hetero-oligomeric interactions between G-protein-coupled receptors in
      living cells monitored by two variants of bioluminescence resonance energy
      transfer (BRET): hetero-oligomers between receptor subtypes form more efficiently
      than between less closely related sequences.
AB  - Homo- and hetero-oligomerization of G-protein-coupled receptors (GPCRs) were
      examined in HEK-293 cells using two variants of bioluminescence resonance energy
      transfer (BRET). BRET(2) (a variant of BRET) offers greatly improved separation
      of the emission spectra of the donor and acceptor moieties compared with
      traditional BRET. Previously recorded homo-oligomerization of the human delta
      opioid receptor was confirmed using BRET(2). Homo-oligomerization of the kappa
      opioid receptor was observed using both BRET techniques. Both homo- and hetero
      oligomers, containing both delta- and kappa-opioid receptors, were unaffected by
      the presence of receptor ligands. BRET detection of opioid receptor homo- and
      hetero-oligomers required expression of 50,000-100,000 copies of the receptor
      energy acceptor construct per cell. The effectiveness of delta-kappa-opioid
      receptor hetero-oligomer formation was as great as for homomeric interactions.
      The capacity of the two opioid receptors to form oligomeric complexes with the
      beta(2)-adrenoceptor was also assessed. Although such interactions were detected,
      at least 250,000 copies per cell of the energy acceptor were required.
      Requirement for high levels of receptor expression was equally pronounced in
      attempts to measure hetero-oligomer formation between the kappa-opioid receptor
      and the thyrotropin-releasing hormone receptor-1. These studies indicate that
      constitutively formed homo- and hetero-oligomers of opioid receptor subtypes can
      be detected in living cells containing less than 100,000 copies of the receptors.
      However, although hetero-oligomeric interactions between certain less closely
      related GPCRs can be detected, they appear to be of lower affinity than homo- or
      hetero-oligomers containing closely related sequences. Interactions recorded
      between certain GPCR family members in heterologous expression systems are likely
      to be artefacts of extreme levels of overexpression.

PMID- 11971763
TI  - Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt
      pathway in normal and tumoral epithelial cells.
AB  - The androgen receptor (AR) is a ligand-responsive transcription factor known to
      play a central role in the pathogenesis of prostate cancer. However, the
      regulation of AR gene expression in the normal and pathological prostate remains
      poorly understood. This study focuses on the effect of the phosphoinositide 3
      kinase (PI 3-kinase)/Akt axis on AR expression in vas deferens epithelial cells
      (VDEC), a suitable model to study androgen regulation of gene expression, and
      LNCaP cells (derived from a metastasis at the left supraclavicular lymph node
      from a 50-year-old patient with a confirmed diagnosis of metastatic prostate
      carcinoma). Taken together, our data show for the first time that the PI 3
      kinase/Akt pathway is required for basal and dihydrotestosterone-induced AR
      protein expression in both VDEC and LNCaP. Inhibition of the PI 3-kinase/Akt
      pathway reduced AR expression and the decline in AR protein level correlated with
      a decrease in AR mRNA in VDEC but not in LNCaP. Since PI 3-kinase/Akt axis is
      active in prostate cancer, cross-talk between PI 3-kinase/Akt and AR signalling
      pathways may have implications for endocrine therapy.

PMID- 11971764
TI  - Feline host range of canine parvovirus: recent emergence of new antigenic types
      in cats.
AB  - Since the emergence of Canine parvovirus (CPV-2) in the late 1970s, CPV-2 has
      evolved consecutively new antigenic types, CPV-2a and 2b. Although CPV-2 did not
      have a feline host range, CPV-2a and 2b appear to have gained the ability to
      replicate in cats. Recent investigations demonstrate the prevalence of CPV-2a and
      2b infection in a wide range of cat populations. We illustrate the pathogenic
      potential of CPV in cats and assess the risk caused by CPV variants.

PMID- 11971765
TI  - Antimicrobial use and antimicrobial resistance: a population perspective.
AB  - The need to stem the growing problem of antimicrobial resistance has prompted
      multiple, sometimes conflicting, calls for changes in the use of antimicrobial
      agents. One source of disagreement concerns the major mechanisms by which
      antibiotics select resistant strains. For infections like tuberculosis, in which
      resistance can emerge in treated hosts through mutation, prevention of
      antimicrobial resistance in individual hosts is a primary method of preventing
      the spread of resistant organisms in the community. By contrast, for many other
      important resistant pathogens, such as penicillin-resistant Streptococcus
      pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant
      Enterococcus faecium resistance is mediated by the acquisition of genes or gene
      fragments by horizontal transfer; resistance in the treated host is a relatively
      rare event. For these organisms, indirect, population-level mechanisms of
      selection account for the increase in the prevalence of resistance. These
      mechanisms can operate even when treatment has a modest, or even negative, effect
      on an individual host's colonization with resistant organisms.

PMID- 11971766
TI  - Baylisascaris procyonis: an emerging helminthic zoonosis.
AB  - Baylisascaris procyonis, a roundworm infection of raccoons, is emerging as an
      important helminthic zoonosis, principally affecting young children. Raccoons
      have increasingly become peridomestic animals living in close proximity to human
      residences. When B. procyonis eggs are ingested by a host other than a raccoon,
      migration of larvae through tissue, termed larval migrans, ensues. This larval
      infection can invade the brain and eye, causing severe disease and death. The
      prevalence of B. procyonis infection in raccoons is often high, and infected
      animals can shed enormous numbers of eggs in their feces. These eggs can survive
      in the environment for extended periods of time, and the infectious dose of B.
      procyonis is relatively low. Therefore, the risk for human exposure and infection
      may be greater than is currently recognized.

PMID- 11971767
TI  - Megadrought and megadeath in 16th century Mexico.
AB  - The native population collapse in 16th century Mexico was a demographic
      catastrophe with one of the highest death rates in history. Recently developed
      tree-ring evidence has allowed the levels of precipitation to be reconstructed
      for north central Mexico, adding to the growing body of epidemiologic evidence
      and indicating that the 1545 and 1576 epidemics of cocoliztli (Nahuatl for
      "pest") were indigenous hemorrhagic fevers transmitted by rodent hosts and
      aggravated by extreme drought conditions.

PMID- 11971768
TI  - Sampling bias in the molecular epidemiology of tuberculosis.
AB  - Among the goals of the molecular epidemiology of infectious disease are to
      quantify the extent of ongoing transmission of infectious agents and to identify
      host- and strain-specific risk factors for disease spread. I demonstrate the
      potential bias in estimates of recent transmission and the impact of risk factors
      for clustering by using computer simulations to reconstruct populations of
      tuberculosis patients and sample from them. The bias consistently results in
      underestimating recent transmission and the impact of risk factors for recent
      transmission.

PMID- 11971769
TI  - A waterborne outbreak of Escherichia coli O157:H7 infections and hemolytic uremic
      syndrome: implications for rural water systems.
AB  - In the summer of 1998, a large outbreak of Escherichia coli O157:H7 infections
      occurred in Alpine, Wyoming. We identified 157 ill persons; stool from 71 (45%)
      yielded E. coli O157:H7. In two cohort studies, illness was significantly
      associated with drinking municipal water (town residents: adjusted odds
      ratio=10.1, 95% confidence intervals [CI]=1.8-56.4; visitors attending family
      reunion: relative risk=9.0, 95% CI=1.3-63.3). The unchlorinated water supply had
      microbiologic evidence of fecal organisms and the potential for chronic
      contamination with surface water. Among persons exposed to water, the attack rate
      was significantly lower in town residents than in visitors (23% vs. 50%, p<0.01)
      and decreased with increasing age. The lower attack rate among exposed residents,
      especially adults, is consistent with the acquisition of partial immunity
      following long-term exposure. Serologic data, although limited, may support this
      finding. Contamination of small, unprotected water systems may be an increasing
      public health risk.

PMID- 11971770
TI  - Biofilm on ventriculo-peritoneal shunt tubing as a cause of treatment failure in
      coccidioidal meningitis.
AB  - We describe a case of recurrent coccidioidal meningitis in which a fungal biofilm
      on the tip of ventriculo-peritoneal shunt tubing was likely responsible for a 4
      year persistence of Coccidioides immitis, despite the patient's taking an
      adequate dosage of fluconazole. Fungal biofilms should be considered as a cause
      for treatment failure and fungal persistence, especially when artificial
      prostheses or indwelling catheters are present.

PMID- 11971771
TI  - Experimental infection of horses with West Nile virus.
AB  - A total of 12 horses of different breeds and ages were infected with West Nile
      virus (WNV) via the bites of infected Aedes albopictus mosquitoes. Half the
      horses were infected with a viral isolate from the brain of a horse (BC787), and
      half were infected with an isolate from crow brain (NY99-6625); both were NY99
      isolates. Postinfection, uninfected female Ae. albopictus fed on eight of the
      infected horses. In the first trial, Nt antibody titers reached >1:320, 1:20,
      1:160, and 1:80 for horses 1 to 4, respectively. In the second trial, the seven
      horses with subclinical infections developed Nt antibody titers >1:10 between
      days 7 and 11 post infection. The highest viremia level in horses fed upon by the
      recipient mosquitoes was approximately 460 Vero cell PFU/mL. All mosquitoes that
      fed upon viremic horses were negative for the virus. Horses infected with the
      NY99 strain of WNV develop low viremia levels of short duration; therefore,
      infected horses are unlikely to serve as important amplifying hosts for WNV in
      nature.

PMID- 11971772
TI  - Salmonella enterica serotype Typhimurium DT104 isolated from humans, United
      States, 1985, 1990, and 1995.
AB  - First isolated from an ill person in 1985, multidrug-resistant Salmonella
      enterica serotype Typhimurium DT104 emerged in the mid-1990s as a strain of
      Salmonella frequently isolated from humans in the United States. We compared the
      integron content, plasmid profile, and XbaI pulsed-field gel electrophoresis
      (PFGE) patterns of multidrug-resistant S. Typhimurium DT104 (MR-DT104) isolated
      from humans in the United States in 1985, 1990, and 1995. All isolates contained
      a 60-mDa plasmid and had indistinguishable PFGE and integron profiles, supporting
      the idea of a clonal relationship between recent and historical isolates. The
      data suggest that the widespread emergence of MR-DT104 in humans and animals in
      the 1990s may have been due to the dissemination of a strain already present in
      the United States rather than the introduction of a new strain.

PMID- 11971773
TI  - Introduction of West Nile virus in the Middle East by migrating white storks.
AB  - West Nile virus (WNV) was isolated in a flock of 1,200 migrating white storks
      that landed in Eilat, a town in southern Israel, on August 26, 1998. Strong, hot
      westerly winds had forced the storks to fly under considerable physical stress
      before reaching the agricultural land surrounding the town. Most of the flock
      were fledglings, <1 year old, which had hatched in Europe. Thirteen dead or dying
      storks were collected 2 days after arrival and submitted to the laboratory for
      examination. Four WNV isolates were obtained from their brains. Out of 11 storks
      tested six days after arrival, three had WNV-neutralizing antibodies. Comparative
      analysis of full-length genomic sequences of a stork isolate and a 1999 flamingo
      isolate from the USA showed 28 nucleotide (nt) (0.25%) and 10 amino acid (0.3%)
      changes. Sequence analysis of the envelope gene of the stork isolate showed
      almost complete identity with isolates from Israeli domestic geese in 1998 and
      1999 and from a nonmigrating, white-eyed gull in 1999. Since these storks were
      migrating southwards for the first time and had not flown over Israel, we assume
      that they had become infected with WNV at some point along their route of
      migration in Europe.

PMID- 11971774
TI  - Outcomes of treated human granulocytic ehrlichiosis cases.
AB  - We conducted a case-control study in Wisconsin to determine whether some patients
      have long-term adverse health outcomes after antibiotic treatment for human
      granulocytic ehrlichiosis (HGE). A standardized health status questionnaire was
      administered to patients and controls matched by age group and sex. Consenting
      patients provided blood samples for serologic testing. Among the 85 previously
      treated patients, the median interval since onset of illness was 24 months.
      Compared with 102 controls, patients were more likely to report recurrent or
      continuous fevers, chills, fatigue, and sweats. Patients had lower health status
      scores than controls for bodily pain and health relative to 1 year earlier, but
      there was no significant difference in physical functioning, role limitations,
      general health, or vitality measures. The HGE antibody titer remained elevated in
      one patient; two had elevated aspartate aminotransferase levels. HGE may cause a
      postinfectious syndrome characterized by constitutional symptoms without
      functional disability or serologic evidence of persistent infection.

PMID- 11971775
TI  - Laboratory reporting of Staphylococcus aureus with reduced susceptibility to
      vancomycin in United States Department of Veterans Affairs facilities.
AB  - A national survey was sent to all appropriate Veterans Health Administration (VA)
      medical facilities asking about the ability to test for Staphylococcus aureus
      with reduced susceptibility to vancomycin (SARV) (MICs >4 microg/mL). For those
      with this ability, a request was made for the number of patients having SARV
      isolated during a 1-year period. Nineteen patients from eight sites across the
      country had isolation of SARV. Of these, MicroScan (Dade Behring, Inc, MicroScan
      Division, West Sacramento, CA) technology was used for 17 patients, Vitek
      (Hazelwood, MO) was used for 1 of the remaining 2 patients, and E-test (AB
      Biiodisk North America, Inc, Piscataway, NJ) for the other. All patients with
      this organism had microbiology testing done onsite in the reporting VA facility's
      College of American Pathologists-approved laboratory. For comparison, similar
      data were obtained for a 1-year period 2 years prior to the current survey; seven
      patients from four sites were verified to have a SARV. Between the two survey
      periods the reported cases of SARV increased 170%, indicating a need for
      continued surveillance and potentially a need to initiate a collection of
      isolates for further analysis.

PMID- 11971776
TI  - Genetic and antigenic analysis of the first A/New Caledonia/20/99-like H1N1
      influenza isolates reported in the Americas.
AB  - From February through May of 1999, 13 cases of Influenza A virus (FLUAV), type
      H1N1 were reported at a Department of Defense influenza surveillance sentinel
      site in Lima, Peru. Genetic and antigenic analysis by hemagglutination inhibition
      and direct nucleotide sequencing of the HA1 region of the hemagglutinin gene were
      performed on two isolates, A/Peru/1641/99 and A/Peru/1798/99. Both isolates were
      distinct from the Bayern/7/95-like viruses circulating in the Americas and
      closely related to a Beijing/262/95-like variant, A/New Caledonia/20/99. With the
      exception of travel-related cases, the detection of these isolates represents the
      first appearance of New Caledonia/20/99-like viruses in the Americas. Since the
      characterization of these Peru isolates, a number of New Caledonia/20/99-like
      viruses have been reported worldwide. For the 2000/01 and 2001/02 influenza
      seasons, the World Health Organization (WHO) has recommended the inclusion of
      A/New Caledonia/20/99 as the H1N1 vaccine component for both the southern and
      northern hemispheres.

PMID- 11971777
TI  - European bat lyssavirus infection in Spanish bat populations.
AB  - From 1992 to 2000, 976 sera, 27 blood pellets, and 91 brains were obtained from
      14 bat species in 37 localities in Spain. Specific anti-European bat lyssavirus 1
      (EBL1)-neutralizing antibodies have been detected in Myotis myotis, Miniopterus
      schreibersii, Tadarida teniotis, and Rhinolophus ferrumequinum in the region of
      Aragon and the Balearic Islands. Positive results were also obtained by nested
      reverse transcription-polymerase chain reaction on brain, blood pellet, lung,
      heart, tongue, and esophagus-larynx-pharynx of M. myotis, Myotis nattereri, R.
      ferrumequinum, and M. schreibersii. Determination of nucleotide sequence
      confirmed the presence of EBL1 RNA in the different tissues. In one colony, the
      prevalence of seropositive bats over time corresponded to an asymmetrical curve,
      with a sudden initial increase peaking at 60% of the bats, followed by a gradual
      decline. Banded seropositive bats were recovered during several years, indicating
      that EBL1 infection in these bats was nonlethal. At least one of this species (M.
      schreibersii) is migratory and thus could be partially responsible for the
      dissemination of EBL1 on both shores of the Mediterranean Sea.

PMID- 11971778
TI  - Invasive group a streptococcal infections, Israel.
AB  - We conducted a prospective, nationwide, population-based study of invasive group
      A streptococcal infections in Israel. We identified 409 patients (median age 27
      years; range <1-92), for an annual incidence of 3.7/100,000 (11/100,000 in
      Jerusalem). The mortality rate was 5%. Bacteremia occurred in 125 cases (31%).
      The most common illnesses were soft-tissue infection (63%) and primary bacteremia
      (14%). Thirty percent of patients had no identifiable risk factors for infection.
      Eighty-seven percent of pharyngeal carriers had the same serotype as the index
      patient. M types included M3 (25%), M28 (10%), and M-nontypable (33%). A marked
      paucity of M1 serotype (1.2%) was detected. The results highlighted concentrated
      pockets of invasive disease in the Jewish orthodox community (annual incidence
      16/100,000).

PMID- 11971779
TI  - Mapping Lyme disease incidence for diagnostic and preventive decisions, Maryland.
AB  - To support diagnostic and preventive decision making, we analyzed incidence of
      Lyme disease in Maryland on the zip code level. Areas of high incidence were
      identified on the Upper Eastern Shore of the Chesapeake Bay and in counties north
      and east of Baltimore City. These latter foci, especially, are not visible when
      mapping Lyme disease on the county level.

PMID- 11971780
TI  - Salmonella enterica serotype Typhimurium DT 104 antibiotic resistance genomic
      island I in serotype paratyphi B.
AB  - We have identified Salmonella genomic island I (SGI1) in an isolate of Salmonella
      enterica serotype Paratyphi B. This antibiotic-resistance gene cluster, which
      confers multidrug resistance, has been previously identified in S. enterica
      serotype Typhimurium phage types DT 104 and DT 120 and in S. enterica serotype
      Agona.

PMID- 11971781
TI  - Multiply resistant (MR) Salmonella enterica serotype Typhimurium DT 12 and DT
      120: a case of MR DT 104 in disguise?
AB  - Multiresistant Salmonella enterica serotype Typhimurium definitive phage type
      (DT) 12 and DT 120 are more closely related to DT 104 than to non-multiresistant
      strains of their respective phage types. Multiresistant DT 12 and DT 120 appear
      to have arisen due to changes in phage susceptibility of DT 104 rather than
      horizontal transfer of resistance genes.

PMID- 11971782
TI  - Andes virus and first case report of Bermejo virus causing fatal pulmonary
      syndrome.
AB  - Two suspected hantavirus pulmonary syndrome (HPS) cases from Bolivia occurred in
      May and July 2000 and were confirmed by enzyme-linked immunosorbent assay (ELISA)
      ANDES using N-Andes recombinant antigen serology. Clot RNAs from the two patients
      were subjected to reverse transcription-polymerase chain reaction (PCR)
      amplification and sequencing. We describe two characterized cases of HPS. One was
      caused by infection with Bermejo virus and the other with Andes Nort viral
      lineage, both previously obtained from Oligoryzomys species. This is the first
      report of molecular identification of a human hantavirus associated with Bermejo
      virus.

PMID- 11971783
TI  - Salmonella enterica serotype Enteritidis phage type 4b outbreak associated with
      bean sprouts.
AB  - In November 2000 in the Netherlands, an outbreak of Salmonella enterica serotype
      Enteritidis phage type 4b was investigated. Eating bean sprouts was the only
      exposure associated with S. Enteritidis pt 4b infection (matched odds ratio 13.0,
      95% confidence interval 2.0-552.5). Contaminated seeds were the most likely cause
      of contamination of the sprouts. The sprout grower applied a concentration of
      hypochlorite solution that was too low for seed disinfection.

PMID- 11971784
TI  - Candida dubliniensis infection, Singapore.

PMID- 11971786
TI  - Proceeding of the Engineering Society Conference on Molecular Electronics.
      December 2000. Kona, Hawaii, USA.

PMID- 11971785
TI  - O157:H7 Shiga toxin-producing Escherichia coli strains associated with sporadic
      cases of diarrhea in Sao Paulo, Brazil.

PMID- 11971787
TI  - Ferroelectric molecular films for nanoscopic ultrahigh-density memories.
AB  - The formation and visualization of nanometer-scale polarized domains in ultrathin
      ferroelectric molecular films by scanning-probe microscopy are described. These
      operations to the ferroelectric domains correspond to the "writing" and the
      "reading" process, respectively, for the data-storage application. In addition,
      nanometer-scale structures and the local electrical properties of the local
      domains, including the interface effect, are discussed. The achieved minimum
      diameter of the written ferroelectric domains was 30 nm. The size of the
      "recording" dot corresponds to the recording density of about 230 Gbit/in.(2).
      The "erasing" process by switching domains was also demonstrated. Furthermore,
      nanometer-scale ferroelectric domains using VDF oligomer molecular films were
      successfully formed, which has opened the way to the control of single molecular
      dipoles.

PMID- 11971789
TI  - Metallosupramolecular coordination polyelectrolytes: potential building blocks
      for molecular-based devices.
AB  - Metal-ion-induced self-assembly of ditopic ligands, based on bisterpyridines, and
      transition metal ions result in formation of metallosupramolecular coordination
      polyelectrolytes (MEPE). The positive charge of MEPE can be utilized in several
      ways to process highly ordered architectures. Alternating adsorption of MEPE and
      oppositely charged polyelectrolytes on solid substrates results in multilayers.
      The sequential nature of this process allows combining MEPEs with other
      functional components. This process permits nanometer thickness control, is
      readily adapted for automated processing, and is applicable to two-dimensional
      substrates as well as to colloidal templates. The surface chemical properties of
      MEPE are readily controlled by complexing MEPE with negatively charged
      amphiphiles. The resulting polyelectrolyte-amphiphile complexes (PAC) are soluble
      in organic solvents and form liquid crystalline phases. The PAC also spreads at
      the air-water interface as Langmuir monolayer, which can be transferred onto
      solid substrates. The resulting Langmuir-Blodgett multilayers are highly ordered
      and anisotropic. Materials with transition metal ions possess many interesting
      properties, including spin transitions, magnetism, as well as photochemical
      assets that are relevant for the construction of functional devices and
      materials. The presented approach combines principles of supramolecular and
      colloidal chemistry as well as surface science, is highly modular in nature, and
      provides extensive control of structure and function from molecular to
      macroscopic levels.

PMID- 11971788
TI  - Electron transfer through bridging molecular structures.
AB  - Pairs of reducible pentakis(thiophenyl)benzene subunits are linked by different
      molecular structures as model compounds for reducible molecular-wire-type
      synthons showing varying electron-transfer ability as a function of the bridging
      structures, consisting of either para-divinylbenzene, bis-hydrazone, or
      diacetylene. Their electron-transfer ability from one reducible subunit to the
      other was investigated by electrochemical and spectroelectrochemical methods. In
      the case of the bis-hydrazone bridge and the diacetylene bridge, the solid-state
      structures support the experimental findings. While the para-divinylbenzene
      bridge completely isolates the reducible subunits (class I system) the
      diacetylene bridge electronically connects the two reducible structures (class
      III system), demonstrating its potential application as a "molecular wire." The
      bis-hydrazone linked dimer displays electronic communication only to a small
      extend, which was only observed in the spectroelectrochemical investigation. The
      diacetylene connection as active electron-transfer linker together with
      poly(thiophenyl)benzene as reducible subunits was used to design more complex
      molecular architectures. Linear rodlike structures did allow adjustment of the
      length of these type of molecular wires and investigation of the extent of
      electron mobility. Cyclic structures addressed the possibility of moving
      electrons on a bent molecular wire.

PMID- 11971790
TI  - Prospects for single-molecule information-processing devices for the next
      paradigm.
AB  - Present information technologies use semiconductor devices and magnetic/optical
      disks; however, they are all foreseen to face fundamental limitations within a
      decade. Therefore, superceding devices are required for the next paradigm of high
      performance information technologies. The paper first describes architectures
      suitable for single-molecule information processing, in which it is claimed that
      the performance of information processing is higher if speed and element number
      product is larger in almost all known architectures. Thus, single-molecule
      information-processing devices should be the most appropriate approach for the
      next paradigm. Then, prospects for single-molecule devices suitable for future
      information-processing technologies are described. Four possible milestones for
      realizing the Peta/Exa-floating operations per second (FLOPS) personal molecular
      supercomputer are proposed. Current status and necessary technologies of the
      first milestone are described, and necessary technologies for the next three
      milestones are also discussed.

PMID- 11971791
TI  - Nonlinear transport through a nanoscale molecule.
AB  - A simple model of electrical transport through a metal-aromatic molecule-metal
      system that includes charging effects as well as aspects of the electronic
      structure of the molecule, is presented. The interplay of a large charging energy
      and an asymmetry of the metal-molecule coupling can lead to various effects in
      nonlinear electrical transport. In particular, strong negative differential
      conductance is observed under certain conditions.

PMID- 11971792
TI  - Molecular wires, switches, and memories.
AB  - Design and measurements of molecular wires, switches, and memories offer an
      increased device capability with reduced elements. We report: Measurements on
      through-bond electronic transport properties of nanoscale metal-1,4-phenylene
      diisocyanide-metal junctions are reported, where nonohmic thermionic emission is
      the dominant process, with isocyanide-Pd showing the lowest thermionic barrier of
      0.22 eV; robust and large reversible switching behavior in an electronic device
      that utilizes molecules containing redox centers as the active component,
      exhibiting negative differential resistance (NDR) and large on-off peak-to-valley
      ratio (PVR) are realized; erasable storage of higher conductivity states in these
      redox-center-containing molecular devices are observed; and a two-terminal
      electronically programmable and erasable molecular memory cell with long bit
      retention time is demonstrated.

PMID- 11971793
TI  - An atomistic approach to conduction between nanoelectrodes through a single
      molecule.
AB  - Capacitance and other properties of nanoelectrodes, finite-size metal clusters
      envisaged for use in complex molecular-electronic devices, are discussed. The
      applicability of classical electrostatics (Coulomb's and Gauss' law, Poisson's
      equation, etc.) to atomistic systems is investigated and the self-energy
      necessary to store a finite charge on an atom is found to be of central
      importance. In particular, the neglect of electron exchange is found to introduce
      severe limitations, with quantum calculations predicting fundamentally different
      electronic structures. Also, the well-known poor representation of the atomic
      self-energy inherent to modern DFT is discussed, along with its implications for
      molecular electronics calculations. An INDO/S method is introduced with new
      parameters for gold. This is the simplest approximate computational scheme that
      correctly includes quantum electrostatic, resonance, and spin effects, and is
      capable of describing arbitrary excited electronic states. Encouraging results
      are obtained for some trial problems. In particular, voltage differential between
      the electrodes in electrode-molecule-electrode conduction is obtained, not
      through an a priori prescription but rather by moving whole electrons between the
      electrodes and analyzing the response. The voltage drops across the molecule
      electrode junctions and the central molecular region are then deduced. This
      alternative to the current Landauer-based 1-particle transmission equations for
      electrode-molecule-electrode conduction is discussed in terms of the use of the
      electronic states of the system. It provides a proper description not only of
      conduction via electrode-to-molecule charge or hole transfer but also of
      conduction via simultaneous charge and hole transfer via low-lying excited
      molecular electronic states, including the ability to account for
      electroluminescence and other chemical effects. In addition, various aspects of
      our research on the quantitative prediction of the I(V) curves for electrode
      molecule-electrode conduction are reviewed, including demonstration of the
      equivalence of the formalisms generated by the Datta and the Mujica-Ratner
      groups, and the development of analytically solvable paradigms, including the
      conduction through a linear-chain Huckel wire.

PMID- 11971794
TI  - Charging effects, forces, and conduction in molecular wire systems.
AB  - Recently, experiments have shown that effects arising from charging and
      conformational changes in a molecular wire due to an applied voltage bias can
      have a significant influence on the transport characteristics of the system. We
      introduce a tractable theoretical approach based on Landauer theory and total
      energy methods that treats transport nonlinearities, conformational changes, and
      charging effects in molecular wires in a unified way. We apply this approach to
      molecular wires consisting of short chain molecules with different electronic and
      structural properties bonded to metal contacts. We find that the nonlinear
      conductance characteristics of these systems are remarkably similar and can be
      understood in terms of a single physical mechanism. We predict that negative
      differential resistance should occur at high bias in such molecular wires due to
      the combined effects of charging and conformational changes on their electronic
      structure.

PMID- 11971795
TI  - Tunneling through a tilted tight-binding band.
AB  - In the single-band approximation, an explicit expression of the exponential
      factor, that governs tunneling through a thin crystal subjected to a constant
      electric field, is derived. The basic features of Wannier-Stark, Airy, and
      intermediate type of quantization, as they are displayed in the transmission
      spectrum and hence in tunneling current, are thus described analytically.

PMID- 11971796
TI  - Interplay of topology and chemical stability on the electronic transport of
      molecular junctions.
AB  - The coherent electronic transport through molecular junctions is theoretically
      modeled. The interplay of geometry, topology, and chemistry is explored within
      the Landauer picture of elastic scattering and various methods of quantum
      description of the composite system. The emphasis is on obtaining guiding
      principles for device optimization. Outstanding problems and future directions
      are outlined.

PMID- 11971798
TI  - First-principles simulations of molecular electronics.
AB  - This paper gives an overview of recent work by the authors in first-principles,
      parameter-free calculations of electronic transport in molecules in the context
      of experimental measurements of current-voltage (I-V) characteristics of several
      molecules by Reed et al. The results show that the shape of I-V characteristics
      is determined by the electronic structure of the molecule in the presence of the
      external voltage, whereas the absolute magnitude of the current is determined by
      the chemistry of individual atoms at the contacts. A three-terminal device has
      been simulated, showing gain. Finally, recent data that show large negative
      differential resistance and a peak that shifts substantially as a function of
      temperature have been accounted for in terms of rotations of ligands attached to
      the main molecule, a phenomenon that is not present in semiconductor
      nanostructures.

PMID- 11971799
TI  - Biomolecular electronic devices based on self-organized deoxyguanosine
      nanocrystals.
AB  - We report on a new class of hybrid electronic devices based on a DNA nucleoside
      (deoxyguanosine lipophilic derivative) whose assembled polymeric ribbons
      interconnect a submicron metallic gate. The device exhibits large conductivity at
      room temperature, rectifying behavior and strong current-voltage hysteresis. The
      transport mechanism through the molecules is investigated by comparing films with
      different self-assembling morphology. We found that the main transport mechanism
      is connected to pi-pi interactions between guanosine molecules and to the
      formation of a strong dipole along ribbons, consistently with the results of our
      first-principles calculations.

PMID- 11971800
TI  - Geometrical factors in conductance through molecular films.
AB  - We have studied the conductance of molecular films as a function of orientation
      of the molecules in the film with respect to electrodes. Depending on the angle
      between the axis of the molecules and the normal to the electrode, the
      conductance may change by more than an order of magnitude. This is a consequence
      of the strong directional character of p orbitals that determine the conductance
      through the conjugated molecules. We illustrate this general result on an exactly
      solvable model and also present the calculations for two different experimentally
      studied molecular films sandwiched between gold electrodes.

PMID- 11971801
TI  - Single-walled carbon nanotubes: from fundamental studies to new device concepts.
AB  - Single-walled carbon nanotubes (SWNTs) are ideal systems for investigating
      fundamental properties in one-dimensional electronic systems and have the
      potential to revolutionize many aspects of nano/molecular electronics. Scanning
      tunneling microscopy (STM) has been used to characterize the atomic structure and
      tunneling density of states of individual SWNTs. Detailed spectroscopic
      measurements showed one-dimensional singularities in the SWNT density of states
      for both metallic and semiconducting nanotubes. The results obtained were
      compared to and agree well with theoretical predictions and tight-binding
      calculations. SWNTs were also shortened using the STM to explore the role of
      finite size, which might be exploited for device applications. Segments less than
      10 nm exhibited discrete peaks in their tunneling spectra, which correspond to
      quantized energy levels, and whose spacing scales inversely with length. Finally,
      the interaction between magnetic impurities and electrons confined to one
      dimension was studied by spatially resolving the local electronic density of
      states of small cobalt clusters on metallic SWNTs. Spectroscopic measurements
      performed on and near these clusters exhibited a narrow peak near the Fermi level
      that has been identified as a Kondo resonance. In addition, spectroscopic studies
      of ultrasmall magnetic nanostructures, consisting of small cobalt clusters on
      short nanotube pieces, exhibited features characteristic of the bulk Kondo
      resonance, but also new features due to their finite size.

PMID- 11971802
TI  - Molecular wire-nanotube interfacial effects on electron transport.
AB  - We discuss the conductance of a molecular bridge between mesoscopic electrodes
      supporting low-dimensional transport and bearing an internal structure. As an
      example for such nanoelectrodes we assume semi-infinite (carbon) nanotubes. In
      the Landauer scattering matrix approach, we show that the conductance of this
      hybrid is very sensitive to the geometry of the contact, unlike the usual
      behavior in the presence of bulk electrodes.

PMID- 11971805
TI  - Egg energetics for the facultative planktotroph Clypeaster rosaceus
      (Echinodermata: Echinoidea), revisited.

PMID- 11971806
TI  - Twin meiosis 2 spindles form after suppression of polar body 1 formation in
      oocytes of the marine shrimp Sicyonia ingentis.

PMID- 11971807
TI  - Evolution of cannabinoid receptors in vertebrates: identification of a CB(2) gene
      in the puffer fish Fugu rubripes.

PMID- 11971808
TI  - Reliable, responsive pacemaking and pattern generation with minimal cell numbers:
      the crustacean cardiac ganglion.
AB  - Investigations of the electrophysiology of crustacean cardiac ganglia over the
      last half-century are reviewed for their contributions to elucidating the
      cellular mechanisms and interactions by which a small (as few as nine cells)
      neuronal network accomplishes extremely reliable, rhythmical, patterned
      activation of muscular activity-in this case, beating of the neurogenic heart.
      This ganglion is thus a model for pacemaking and central pattern generation.
      Favorable anatomy has permitted voltage- and space-clamp analyses of voltage
      dependent ionic currents that endow each neuron with the intrinsic ability to
      respond with rhythmical, patterned impulse activity to nonpatterned stimulation.
      The crustacean soma and initial axon segment do not support impulse generation
      but integrate input from stretch-sensitive dendrites and electrotonic and
      chemically mediated synapses on axonal processes in neuropils. The soma and
      initial axon produce a depolarization-activated, calcium-mediated, sustained
      potential, the "driver potential," so-called because it drives a train of
      impulses at the "trigger zone" of the axon. Extreme reliability results from
      redundancy and the electrotonic coupling and synaptic interaction among all the
      neurons. Complex modulation by central nervous system inputs and by neurohormones
      to adjust heart pumping to physiological demands has long been demonstrated, but
      much remains to be learned about the cellular and molecular mechanisms of action.
      The continuing relevance of the crustacean cardiac ganglion as a relatively
      simple model for pacemaking and central pattern generation is confirmed by the
      rapidly widening documentation of intrinsic potentials such as plateau potentials
      in neurons of all major animal groups. The suite of ionic currents (a slowly
      inactivating calcium current and various potassium currents, with variations)
      observed for the crustacean cardiac ganglion have been implicated in or proven to
      underlie a majority of the intrinsic potentials of neurons involved in pattern
      generation.

PMID- 11971809
TI  - Timing is everything: the effects of putative dopamine antagonists on
      metamorphosis vary with larval age and experimental duration in the prosobranch
      gastropod Crepidula fornicata.
AB  - The signal transduction pathway through which excess potassium ion stimulates the
      larvae of many marine invertebrates to metamorphose is incompletely understood.
      Recent evidence suggests that dopamine plays important roles in the metamorphic
      pathway of Crepidula fornicata. Therefore, we asked whether blocking dopamine
      receptors might prevent excess potassium ion from stimulating metamorphosis in
      this species. Surprisingly, the effects of the three putative dopamine
      antagonists tested (all at 10 microM) varied with exposure duration and the age
      of competent larvae. Chlorpromazine, a nonspecific dopamine antagonist known to
      have a number of other pharmacological effects, blocked the inductive action of
      excess potassium ion during the initial 5-8-h exposure periods in most assays,
      particularly for younger or smaller competent larvae. However, chlorpromazine in
      the absence of excess potassium ion also stimulated metamorphosis, particularly
      over the next 18 h, and worked faster on older competent larvae than on younger
      competent larvae. The specific D(1) antagonist R(+)-Sch-23309 had similar
      effects, blocking potassium-stimulated metamorphosis in short-term exposures and
      stimulating metamorphosis in longer exposures, particularly for older competent
      larvae. Although the specific D(2) antagonist spiperone (SPIP) blocked the
      inductive effects of excess potassium ion in only 1 of 6 assays during the first
      6 h of exposure, it blocked metamorphosis in 2 of the assays during 24-h
      exposures. Our results indicate that dopamine receptors are involved in the
      pathway through which excess potassium ion stimulates metamorphosis in C.
      fornicata. In addition, the largely latent inductive effects of chlorpromazine,
      an inhibitor of nitric oxide synthase, suggest that endogenous nitric oxide may
      play a natural role in inhibiting metamorphosis in this species. Overall, our
      results would then suggest that exposing larvae of C. fornicata to excess K(+)
      leads to a shutdown of nitric oxide synthesis via a dopaminergic pathway, a
      pathway that can be blocked by some dopamine antagonists. Alternatively,
      chlorpromazine might eventually be stimulating metamorphosis by elevating
      endogenous cyclic nucleotide (e.g., cAMP) concentrations, again acting downstream
      from the steps acted on directly by excess K(+).

PMID- 11971811
TI  - Variation in growth and competitive ability between sexually and clonally
      produced hydroids.
AB  - In controlled laboratory experiments, colonies of Podocoryna carnea typically
      overgrow and kill colonies of Hydractinia symbiolongicarpus. Generally, these
      experiments have used colonies grown from tissue explants (clonal replicates)
      surgically removed from mature colonies taken from natural populations. In
      contrast, experiments involving interspecific bouts between small, sexually
      produced colonies reveal that both the characteristics and outcomes of
      competition differ from previous studies. During competition between small
      sexually produced colonies, H. symbiolongicarpus exhibits directional growth
      toward P. carnea and produces nematocyte-rich hyperplastic stolons more readily
      than P. carnea does. Nevertheless, P. carnea can still overcome H.
      symbiolongicarpus if it initially grows away from the contact zone and
      subsequently flanks H. symbiolongicarpus. Overall, sexually produced colonies of
      H. symbiolongicarpus destroyed their P. carnea counterparts in more than 35% of
      competitive bouts, whereas P. carnea dominated their H. symbiolongicarpus
      counterparts in all similar encounters between clonally produced colonies. In
      natural populations, competition between small sexually produced colonies of H.
      symbiolongicarpus may predominate, and these results support the hypothesis that
      this species is adapted to competition early in colony development. More
      generally, studies of competition between sexually produced colonies should
      complement similar studies of clonally produced colonies.

PMID- 11971810
TI  - Morphometric analysis of male reproductive features of octopodids (Mollusca:
      Cephalopoda).
AB  - Taxonomic accounts of octopodids frequently describe the spermatophore, the penis
      that releases the spermatophore from the internal organs, and the ligula and
      calamus that transfer it to a female. To explore relationships among these male
      features and body size, this study applies principal components analysis to data
      from 43 species of the family Octopodidae, or benthic octopuses. Covariation in
      penis and mantle length opposed by covariation in ligula and calamus lengths
      forms primary shape variation. Secondary shape variation is due to opposing
      variation between ligula and calamus lengths. Primary shape variation is greatest
      among shallow-water species. The calami and ligulae of diurnal and crepuscular
      shallow-water species are short compared to those of nocturnal shallow-water
      species. Because these structures contain heterogeneous collagen arrays and lack
      camouflaging chromatophore organs, they are white. Diurnal and crepuscular
      octopus species may minimize their lengths due to selection imposed by visual
      predators. Secondary shape variation is greater in deep-sea and high-latitude
      octopuses. Members of Voss's Eledoninae (except Eledone) and Graneledoninae and
      two species of Benthoctopus have exceptionally long calami and comparatively
      short ligulae; these lengths vary among members of the Bathypolypodinae.
      Variation in spermatophore length is independent of the structures considered.

PMID- 11971812
TI  - Quantitative analysis of gametic incompatibility between closely related species
      of neotropical sea urchins.
AB  - Species of the sea urchin genus Echinometra found on the two coasts of Panama are
      recently diverged and only partially isolated by incomplete barriers to
      interspecific fertilization. This study confirms previous work that revealed
      incompatibility between the eggs of the Atlantic E. lucunter and the sperm of the
      other two neotropical species, whereas eggs of its sympatric congener E. viridis
      and allopatric E. vanbrunti are largely compatible with heterospecific sperm.
      Here we quantify fertilization using a range of sperm dilutions. We demonstrate a
      much stronger block to cross-species fertilization of E. lucunter eggs than was
      previously shown at fixed sperm concentrations, and mild incompatibility of the
      other two species' eggs where previous crosses between species were not
      distinguishable from within-species controls. Additionally, we present evidence
      for intraspecific variation in egg receptivity towards heterospecific sperm. Our
      findings here again discount the "reinforcement model" as a viable explanation
      for the pattern of prezygotic isolation. Gamete incompatibility in these
      Echinometra has appeared recently-within the last 1.5 million years-but is weaker
      in sympatry than in allopatry. Accidents of history may help explain why
      incompatibility of eggs emerged in one species and not in others. Compensatory
      sexual selection on sperm in this species could follow, and promote divergence of
      proteins mediating sperm-egg recognition.

PMID- 11971813
TI  - The anatomy, life habits, and later development of a new species of enteropneust,
      Harrimania planktophilus (Hemichordata: Harrimaniidae) from Barkley Sound.
AB  - A new species of enteropneust, Harrimania planktophilus, lives intertidally and
      subtidally in mixed sediments in Barkley Sound, British Columbia, Canada. H.
      planktophilus has a long proboscis skeleton extending into the pharyngeal region.
      The collar (mesosome) has complete dorsal and ventral mesenteries. The trunk
      (metasome) has four distinct regions that can be recognized externally: the
      branchial region, esophageal region, hepatic region, and an undifferentiated
      intestinal region leading to the anus. The dorsal pharynx is large and has long
      gill slits without synapticles. Posterior to the gills is a constriction followed
      by a short esophageal region and a long gonadal region. The paired dorsolateral
      gonads extend almost to the end of the trunk. Eggs in the ovaries appear amber
      yellow, and the testes appear slightly paler. The trunk terminates at an anus
      with a well-developed sphincter muscle. H. planktophilus forms long sinuous
      burrows that are semipermanent and shared. Females deposit a tubular egg mass in
      a burrow in which the embryos develop directly into juveniles. Gastrulation
      appears to be by invagination, followed by a ciliated stage that has a
      telotrochal swimming band, suggesting that the ancestor to H. planktophilus
      developed via a tornaria larva. The juveniles emerge from the egg membrane with a
      ventral post-anal tail and assume an interstitial burrowing life habit. The post
      anal tail, mode of development, small size and correlated simplification in body
      plan suggest that H. planktophilus is closely related to Saccoglossus, and
      together these worms may be sister taxa to the colonial Pterobranchia. A
      taxonomic key is provided to the enteropneust genera, and to the species of
      Harrimania:

PMID- 11971814
TI  - Particle retention and flow in the pharynx of the enteropneust worm Harrimania
      planktophilus: the filter-feeding pharynx may have evolved before the chordates.
AB  - An investigation of the feeding behavior of the acorn worm Harrimania
      planktophilus suggests a novel form of enteropneust feeding with significant
      phylogenetic implications. H. planktophilus is a holoinfaunal worm that feeds on
      deposited sediments, and filter feeds on suspended particles in interstitial pore
      water. To visualize the particle retention behavior involved in filter feeding,
      adult animals were held in chilled seawater under low light and fed food coloring
      and fluorescent particles. The behavior was recorded by videography. Most
      particles ingested were drawn into the mouth by an incurrent flow created by
      cilia on the pharyngeal bars and without the aid of mucus. Particles that passed
      freely through the gill pores averaged 3.04 microm, whereas particles retained in
      the gut and defecated in the feces averaged 13.9 microm. Food coloring entered
      the mouth and was pumped through the pharynx at a rate of 0.5-2.0 mm/s. There is
      no evidence of an endostyle or mucus-net capture mechanism in H. planktophilus,
      but instead particles are filtered and manipulated by a dense covering of cilia
      on the pharyngeal gill bars. This study suggests that the filter-feeding pharynx
      is not an innovation of the chordates, but evolved prior to the evolutionary
      divergence of the hemichordate-echinoderm clade from the chordates.

PMID- 11971815
TI  - Methylation matters: modeling a manageable genome.

PMID- 11971816
TI  - Insulin-like growth factor binding protein-3 mediates tumor necrosis factor-alpha
      induced apoptosis: role of Bcl-2 phosphorylation.
AB  - The insulin-like growth factor (IGF)-independent effects of insulin-like growth
      factor binding protein-3 (IGFBP-3) to effect cellular apoptosis have now been
      described in various cellular systems. IGFBP-3 mediates transforming growth
      factor-beta-induced apoptosis. Other growth-inhibitory and apoptosis-inducing
      agents such as tumor necrosis factor-alpha (TNF-alpha) and the tumor suppressor
      gene p53 also induce IGFBP-3. In this report, we demonstrate the role of IGFBP-3
      as a mediator of apoptosis induced by TNF-alpha and elucidate the process
      involved in its signaling mechanism. Treatment of PC-3 cells with TNF-alpha
      resulted in the induction of IGFBP-3 expression in a dose- and time-dependent
      fashion and also induced apoptosis. TNF-alpha-induced apoptosis was prevented by
      cotreatment with IGFBP-3 neutralizing antibodies or IGFBP-3-specific antisense
      thiolated oligonucleotides. Both IGFBP-3 and TNF-alpha treatment increased the
      levels of the inactive, serine phosphorylated form of the survival protein Bcl-2.
      The effect of TNF-alpha on Bcl-2 serine phosphorylation was blocked by IGFBP-3
      antisense oligomers. These findings confirm that IGFBP-3 is essential for TNF
      alpha-induced apoptosis in PC-3 cells and that this IGFBP-3 effect includes the
      inactivation of Bcl-2 through serine phosphorylation.

PMID- 11971818
TI  - c-Myc overexpression increases cell size and impairs cartilage differentiation
      during chick limb development.
AB  - c-Myc is a transcription factor involved in the control of cell proliferation,
      differentiation, and apoptosis, all basic processes for embryogenesis. To analyze
      c-Myc roles in limb development, we overexpressed c-myc in chick embryos using a
      retroviral vector. Forced c-myc expression resulted in enlarged limbs, because of
      an increase in cell size not accompanied by modifications in cell proliferation.
      However, at later stages, limbs overexpressing c-myc showed a marked shortening
      of their skeletal elements, because of the inhibition of chondrocyte maturation.
      c-Myc interfered with chondrogenesis, independently of the Indian
      hedgehog/parathyroid hormone-related protein and Wnt5a/Wnt5b regulatory loops. c
      myc-infected limbs also exhibited patterning defects, such as extra-phalangeal
      elements and delayed interdigital apoptosis that occasionally led to interdigital
      chondrogenesis. In contrast, c-myc overexpression did not interfere with other
      processes, such as muscle differentiation. Although based on overexpression
      experiments, our results suggest that endogenous c-Myc may be implicated in the
      control of cell size and skeletal differentiation during normal limb development.

PMID- 11971817
TI  - The Retinoic acid receptor alpha (RARalpha) chimeric proteins PML-, PLZF-, NPM-,
      and NuMA-RARalpha have distinct intracellular localization patterns.
AB  - Retinoic acid receptor alpha (RARalpha) gene rearrangement by reciprocal
      chromosome translocation is the molecular signature of acute promyelocytic
      leukemia (APL). Disruption of RARalpha function appears to be the likely cause of
      aberrant myelopoiesis observed in APL, because PML-RARalpha expression has been
      shown to deregulate the transcription of genes that control myelopoiesis. To
      target RARalpha chimeric proteins, we engineered epitope-tagged versions of PML
      RARalpha, PLZF-RARalpha, NPM-RARalpha, and NuMA-RARalpha (X-RARalphaV5) and
      generated a panel of stable COS cell lines expressing X-RARalphaV5. Protein
      fractionation and Western analysis of these COS lines reveal that X-RARalpha
      proteins localize to both the cytoplasm and nucleus. NPM-RARalpha is
      predominantly nuclear whereas NuMA-RARalpha is predominantly cytoplasmic.
      Confocal immunofluorescent microscopy reveals that PML-RARalpha and PLZF-RARalpha
      share a primarily diffuse nuclear pattern that excludes the nucleolus. NPM
      RARalpha is also diffuse in the nucleus but, in contrast to PML-RARalpha and PLZF
      RARalpha, is strongly associated with the nucleolus. Strikingly, NuMA-RARalpha
      predominantly localizes throughout the cytoplasm in a microspeckled pattern. We
      further demonstrate that NPM and NuMA interact with NPM-RARalpha and NuMA
      RARalpha, respectively. The distinct intracellular localization patterns and the
      shared ability of X-RARalpha to interact with their respective RARalpha partner
      proteins (X) further support the hypothesis that deregulation of these partners
      may play a role in APL pathogenesis.

PMID- 11971819
TI  - Increased gene expression of lung marker proteins in the homeobox B3
      overexpressed fetal lung cell line M3E3/C3.
AB  - Homeobox (Hox)-containing factors have been shown to play regulatory roles on
      lung development. Although HoxB3 gene expression is detected in the prenatal lung
      during development, its function has not been clarified precisely. We constructed
      an expression vector of a hamster HoxB3 coding region, which was cloned from
      hamster fetal lung cell line M3E3/C3. Sixteen-base deletion was found in the
      hamster HoxB3 coding sequence when compared with the mouse sequence. Under
      conditions of differentiation, cells transfected transiently with HoxB3 augmented
      the retinol-induced gene expression of Clara cell-specific secretory protein,
      whereas the cells showed reduced expression of surfactant-associated protein C.
      These alterations were attenuated by the transfection with HoxB3 antisense
      nucleotide. The results show that the cells with overexpressed HoxB3 were
      reinforced to have characteristics of Clara cells but did not have the
      characteristics of alveolar type II cells, and that HoxB3 played a stimulatory
      role on Clara cell differentiation in M3E3/C3 cells. In addition, the expression
      of Clara cell-specific secretory protein and surfactant-associated protein C
      genes was enhanced upon transfer of cells to collagen substrate, suggesting that
      collagen substrate has some regulatory functions on lung cell differentiation
      through cell adhesion.

PMID- 11971821
TI  - Advances, challenges, and controversies in poisoning.

PMID- 11971822
TI  - Troublesome toxins.

PMID- 11971825
TI  - Emergency analgesia in the paediatric population. Part III non-pharmacological
      measures of pain relief and anxiolysis.

PMID- 11971826
TI  - An introduction to economic evaluation.

PMID- 11971828
TI  - An evidence based flowchart to guide the management of acute salicylate (aspirin)
      overdose.
AB  - OBJECTIVE: To develop a flowchart to be used as a tool to guide clinicians step
      by step through the management of salicylate poisoning. METHODS: A comprehensive
      literature search was carried out. RESULTS: The evidence base was used to develop
      a management flowchart that guides the clinician through the three main steps in
      caring for the patient with salicylate poisoning: preventing further absorption,
      assessing the severity of poisoning and, where appropriate, increasing
      elimination. CONCLUSIONS: Salicylate poisoning can result in severe morbidity and
      mortality and this flowchart provides an evidence based guideline that will guide
      clinicians through the management of patients presenting to the emergency
      department with salicylate poisoning.

PMID- 11971827
TI  - Paracetamol overdose: an evidence based flowchart to guide management.

PMID- 11971829
TI  - Positive blood alcohol concentration and road accidents. A prospective study in
      an Italian emergency department.
AB  - STUDY OBJECTIVE: To examine if a positive blood alcohol concentration (BAC) at
      the time of crash (>or=0.50 g/l), independently of any clinical evidence and
      laboratory results indicating acute alcohol intoxication, is associated with
      specific features of patients involved, specific types of injury, and
      characteristics of the accident. METHODS: In this prospective cohort study, the
      BAC was measured in adult patients who had been injured and who were admitted to
      an Italian emergency department within four hours after a road accident.
      Altogether 2354 trauma patients were included between January to December 1998
      out of 2856 eligible subjects. RESULTS: BAC exceeded 0.50 g/l in 425 subjects
      (18.1%), but was in a toxic range (>1.00 g/l) in only 179 subjects (7.6%). BAC
      positivity was significantly more common in men, in young subjects, in subjects
      driving cars or trucks, and in persons involved in a crash during night time and
      at weekends. It was associated with higher trauma severity, but no differences
      were found in injury body distribution according to vehicle type. In multivariate
      logistic regression analysis, the risk of a positive BAC in injured patients at
      the time of crash was independently associated with night time (odds ratio: 3.48;
      95% confidence intervals: 2.46 to 4.91), male sex (3.08 (2.36 to 4.01)), weekend
      nights (1.21 (1.05 to 1.41)), and age (0.92 (0.86 to 0.99) per decades).
      CONCLUSION: In injured patients after a road accident, a BAC at the time of crash
      in a non-toxic range (>or=0.50 g/l) is associated with specific characteristics
      of crash, as well as increased risk of higher trauma severity. More careful
      monitoring is needed in young men during weekend nights for highest risk of BAC
      positivity after a road accident.

PMID- 11971830
TI  - The development of a computerised equipment and drug calculator for use in
      resuscitation.
AB  - OBJECTIVES: To design a computerised system of calculating resuscitation
      requirements and to test this system to ensure that it gives accurate and fast
      results, so that it could potentially be used in the resuscitation of patients in
      a accident and emergency (A&E) department. METHODS: Using internet based
      technology we have developed a program that runs inside most web browsers and can
      be used to calculate several parameters (including endotracheal tube dimensions
      and drug doses). The only value that is required is the age of the patient. The
      weight is calculated and can be adjusted if known. The resuscitation requirement
      calculations are made from the weight. The program was then tested on staff
      members in the department to calculate theoretical resuscitation requirements for
      paediatric and adult patients. Accuracy and speed of the computerised calculator
      was compared with the conventional paper based calculation methods. RESULTS:
      Subjects performed better using the computerised calculator. On average they made
      significantly fewer errors (21.4% more accurate than using conventional methods)
      and were three times faster. CONCLUSION: The computerised calculator has proved,
      in a controlled setting, to be a more accurate and faster way of calculating
      resuscitation requirements than conventional methods.

PMID- 11971831
TI  - Accidental hypothermia and active rewarming: the metabolic and inflammatory
      changes observed above and below 32 degrees C.
AB  - OBJECTIVES: In accidental hypothermia the underlying physiological mechanisms
      responsible for poor outcome during rewarming through 32 degrees C remain
      obscure, although possible associations include changes in acid-base balance,
      divalent cations, and inflammatory markers. This study investigated the metabolic
      and inflammatory changes that occur during the rewarming of hypothermic patients.
      METHODS: Eight patients, four men and four women, age 45 to 85 years, admitted
      with core temperatures <35 degrees C were included in the study. Patients were
      rewarmed with dry warm blankets and fluid replaced by crystalloid at 40 degrees
      C. Bloods for pH, ionised calcium (Ca(2+)) and magnesium (Mg(2+)), parathyroid
      hormone (PTH), interleukin 1 (IL1), interleukin 6 (IL6), tissue necrosis factor
      alpha (TNFalpha), were collected at presentation, during rewarming, and at 24
      hours. RESULTS: Four patients were admitted with mild (32 degrees -35 degrees C)
      and four with moderate (28 degrees -32 degrees C) hypothermia. Rewarming to 32
      degrees C had no significant effect on the presenting acidosis (p=0.1740),
      although above 32 degrees C pH increased with temperature (p<0.0001). There was a
      negative correlation between pH and both Ca(2+) (p=0.0005) and Mg(2+) (p=0.0488)
      below 32 degrees C; above this temperature the relation was significant only for
      Ca(2+) (p=0.0494). PTH and Ca(2+) correlated positively (p=0.0041) and negatively
      (p=0.0039) below and above 32 degrees C respectively. There was no relation
      between IL1 or TNFalpha with Ca(2+) during rewarming, but IL6 and Ca(2+)
      correlated positively (p=0.0039) and negatively (p=0.0018) when presentation
      temperature was below and above 32 degrees C respectively. CONCLUSIONS: During
      rewarming pH remains unchanged until patient temperature approaches 32 degrees C.
      Ca(2+) and Mg(2+) decline is associated with the pH increase above 32 degrees C.
      Poor outcome is associated with presentation temperature (<32 degrees C), non
      physiological correlation between IL6-PTH-Ca(2+), and age (>or=84 years).

PMID- 11971832
TI  - The effect of gel burns dressings on skin temperature.
AB  - OBJECTIVES: This study was designed to investigate the effect on skin temperature
      of different methods of use of a hydrogel dressing. METHODS: Twelve volunteers
      had temperature measured under a hydrogel dressing with different combinations of
      air movement and bandaging. RESULTS: A large drop in skin temperature was only
      achieved when the dressing was left exposed with air movement over the surface of
      the dressing. CONCLUSIONS: A temperature that gives effective analgesia is not
      reached if the dressing is used in accordance with the manufacturer's
      instructions (covered with an insulating layer). This explains the authors'
      observation that paramedics and patients often leave these dressings uncovered.

PMID- 11971833
TI  - A prospective survey of patients with presumed accidental ear injury presenting
      to a paediatric accident and emergency department.
AB  - OBJECTIVES: To assess the characteristics of assumed accidental ear injury in
      children. METHODS: A prospective survey of 111 children presenting with
      accidental external or internal ear injuries to a paediatric accident and
      emergency department. RESULTS: The majority of patients were male (73%). Right
      and left sided injuries were equally common (51% right, non-bilateral).
      Presentation with accidental ear injury was very rare in children under the age
      of 1 year (n=1). Most patients were self referred (98%), and presented within six
      hours of injury (84%). The mechanism of injury was variable, but cotton bud
      induced injury was common (7%). The most common injuries were lacerations of the
      pinna, in 63 patients (56%). Fourteen per cent had blood in the external canal.
      Only three patients required admission. CONCLUSIONS: Lacerations are the
      commonest form of accidental ear injury. Ear injuries that are bilateral and in
      children less than 1 year of age are rare and may suggest non-accidental injury.
      Cotton bud induced injury is common and preventable.

PMID- 11971834
TI  - The Child Protection Register: a tool in the accident and emergency department?
AB  - AIMS: To determine the number of children on the Child Protection Register (CPR)
      attending the accident and emergency (A&E) department and the referral source,
      diagnostic category, and frequency distribution for such attendances. To
      determine whether lack of knowledge that a child is on the CPR results in failure
      to suspect non-accidental injury (NAI) if the standard indicators of NAI have
      been sought. METHODS: Access to the CPR was obtained. Records of each child
      attending the A&E departments of the United Hospitals Trust between June 1994 and
      May 2000 were reviewed. RESULTS: Over the six years 191 children were on the CPR.
      Seventy nine (41%) attended A&E departments on 206 occasions. Frequency of
      attendance ranged to 18 with a mean of 2.6. Self referral was the commonest
      source of referral (81%) followed by general practitioners (13%), 999 calls (5%),
      and a small number from schools (1%). Most presentations involved trauma-upper
      limb (21%), lower limb (14%), and head injury (8%). Almost all cases of trauma
      were adjudged to be consistent with the history and NAI not suspected. Common
      childhood illnesses accounted for the remainder of presentations. Only six
      children were identified as being on the CPR at the time of presentation.
      Concerns were raised in two other cases and concerns should have been raised in
      three other children. Social Services were alerted on five occasions directly by
      the parents themselves. CONCLUSIONS: It is concluded that in the absence of
      knowledge of the status of a child on the CPR attending the A&E department, that
      screening for the standard indicators of NAI is adequate to detect most cases of
      NAI.

PMID- 11971835
TI  - ASME proposals for reform of SHO training: threat or opportunity for the
      specialty of accident and emergency?

PMID- 11971836
TI  - Occupational stress in consultants in accident and emergency medicine: a national
      survey of levels of stress at work.
AB  - OBJECTIVE: To assess levels of occupational stress in UK accident and emergency
      (A&E) consultants. METHOD: Postal survey of complete enumeration of UK
      consultants. MAIN OUTCOME MEASURES: GHQ-12 and SCL-D, and respondents' reported
      perceptions of stressors. RESULTS: Of 371 valid respondents (78%), 21 declined to
      participate. Of the remaining 350, 154 (44.4%) had GHQ-12 scores over the
      threshold for distress, which is much higher than found in other studies of
      doctors. Levels of depression as measured by the SCL-D at 18% (n=63) were
      slightly higher than other groups. Thirty four (10%) reported suicidal ideation.
      Women had significantly higher SCL-D scores than men (U=6604, p<0.01).
      Respondents were highly satisfied with A&E as a specialty. Protective factors
      found in other occupational groups did not apply. Only one demographic or work
      related factor; number of hours reportedly worked during previous week by
      respondents in full time posts (median=57, interquartile range=57), significantly
      correlated with either stress outcome measure (GHQ-12 scores) (rho=0.126,
      p<0.03). Logistic regression modelling revealed "being overstretched" (OR=1.18),
      "effect of hours (OR=0.82) and stress (OR=1.58) on family life", and "lack of
      recognition" (OR=1.32) were significant predictors of GHQ identified caseness,
      while "the effect of stress on family life" (OR=1.53), low prestige of specialty
      (OR=1.20), and "dealing with management" (OR=1.28) predicted SCL-D scores.
      CONCLUSION: There are high levels of psychological distress among doctors working
      in A&E compared with other groups of doctors. There is likely to be an effect on
      staff morale and career longevity. Interventions to improve the working lives of
      A&E consultants are required, in particular a reduction in hours worked.

PMID- 11971837
TI  - Sports medicine and the accident and emergency medicine specialist.
AB  - BACKGROUND: Sport and exercise related injuries are responsible for about 5% of
      the workload in the accident and emergency (A&E) department, yet training in
      sports medicine is not a compulsory part of the curriculum for Higher Specialist
      Training. AIM: To determine how A&E medicine consultants and specialist trainees
      view their role and skill requirements in relation to sports medicine. METHOD: A
      modified Delphi study, consisting of two rounds of a postal questionnaire.
      Participants were invited to rate the importance of statements relating to the
      role and training of the A&E specialist in relation to sports injuries (six
      statements) and the need for knowledge and understanding of defined skills of
      importance in sports medicine (16 statements). VALUE OF RESEARCH: This provides a
      consensus of opinion on issues in sport and exercise medicine that have
      educational implications for A&E specialists, and should be considered in the
      curriculum for Higher Specialist Training. There is also the potential for
      improving the health care provision of A&E departments, to the exercising and
      sporting population.

PMID- 11971838
TI  - Clinical research in emergency medicine: putting it together.

PMID- 11971841
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Vomiting in paracetamol overdose.
AB  - A short cut review was carried out to establish whether vomiting was a
      significant consequence of paracetamol (acetaminophen) overdose. Altogether 48
      papers were found using the reported search, of which two presented the best
      evidence to answer the clinical question. The author, date and country of
      publication, patient group studied, study type, relevant outcomes, results and
      study weaknesses of these best papers are tabulated. A clinical bottom line is
      stated.

PMID- 11971839
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Oral or intravenous antidote for paracetamol overdose.
AB  - A short cut review was carried out to establish whether there was any evidence to
      decide between oral or intravenous antidote in paracetamol (acetaminophen)
      poisoning. Altogether 330 papers were found using the reported search, of which
      two presented the best evidence to answer the clinical question. The author, date
      and country of publication, patient group studied, study type, relevant outcomes,
      results and study weaknesses of these best papers are tabulated. A clinical
      bottom line is stated.

PMID- 11971842
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Intravenous bolus or infusion of naloxone in opioid overdose.
AB  - A short cut review was carried out to establish whether intravenous boluses of
      naloxone are better than intravenous infusion in opioid overdose. Altogether 188
      papers were found using the reported search, of which one presented the best
      evidence to answer the clinical question. The author, date and country of
      publication, patient group studied, study type, relevant outcomes, results and
      study weaknesses of this best paper is tabulated. A clinical bottom line is
      stated.

PMID- 11971843
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Intravenous or intramuscular/subcutaneous naloxone in opioid overdose.
AB  - A short cut review was carried out to establish whether
      intramuscular/subcutaneous naloxone is better than intravenous naloxone in opioid
      overdose. Altogether 185 papers were found using the reported search, of which
      two presented the best evidence to answer the clinical question. The author, date
      and country of publication, patient group studied, study type, relevant outcomes,
      results and study weaknesses of these best papers are tabulated. A clinical
      bottom line is stated.

PMID- 11971845
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Gastric lavage in iron overdose.
AB  - A short cut review was carried out to establish whether gastric lavage is of use
      after an overdose of ionic compounds. Altogether 74 papers were found using the
      reported search but none answered the question posed.

PMID- 11971844
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Discharge of patients who have taken an overdose of opioids.
AB  - A short cut review was carried out to establish whether patients with no
      recurrence of symptoms one hour after receiving naloxone for an opioid overdose
      can safely be discharged. Altogether 195 papers were found using the reported
      search, of which five presented the best evidence to answer the clinical
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these best papers
      are tabulated. A clinical bottom line is stated.

PMID- 11971846
TI  - Article 8. Quality assurance, clinical governance, and a patient wants to die.

PMID- 11971847
TI  - Prehospital selection of patients for thrombolysis by paramedics.
AB  - OBJECTIVE: Heart disease is the major cause of death in Wales. Myocardial
      infarction accounts for most fatalities either acutely or as a result of late
      heart failure and unheralded sudden cardiac death. Prompt relief of new coronary
      occlusions by thrombolytic agents has been shown to reduce significantly both
      early mortality and subsequent morbidity from acute myocardial infarction. The
      prehospital delivery of these drugs is feasible, and carries no greater risk than
      administration in hospital. This study tests the hypothesis that paramedics can
      identify patients with acute myocardial infarction who are suitable for
      prehospital thrombolysis, and thus reduce the "call to needle" time. METHOD:
      Paramedics from rural Wales were trained in the acquisition and recognition of 12
      lead ECGs, and also in the modified indications for thrombolytic therapy as
      defined by the Joint Royal Colleges Ambulance Liaison Committee (JRCALC). Ninety
      six consecutive patients, with possible myocardial infarction, were included in
      the study. The paramedics made an independent decision regarding the eligibility
      of the patients for thrombolysis before hospital admission, noting the time that
      they could have administered the drug. These decisions were compared with the
      treatment subsequently received in hospital. RESULTS: No errors were made by the
      paramedics in case selection (specificity of 100% (95% CI 95.9% to 100%)). There
      was a potential reduction in call to needle time of 41.2 minutes (95% CI 25.7
      minutes to 56.9 minutes, p=0.001). CONCLUSIONS: It was concluded that the
      paramedic selection of patients for the prehospital administration of a
      thrombolytic is both feasible and safe.

PMID- 11971848
TI  - Cocaine/heroin induced rhabdomyolysis and ventricular fibrillation.
AB  - A case of cardiorespiratory arrest in a 28 year old man after cocaine and heroin
      ingestion is described. The arrest is attributed primarily to
      hyperkalaemia/rhabdomyolysis-a recognised consequence of each of these drugs. The
      administration of naloxone may have been contributory. He developed acute renal
      failure, disseminated intravascular coagulopathy with consequent lower limb
      compartment syndrome requiring fasciotomy. Ventricular fibrillation was
      identified at thoracotomy.

PMID- 11971850
TI  - Toxicity of brake oil.
AB  - Brake oil is an automobile transmission fluid composed of a mixture of toxic
      glycols and glycol ethers. Three cases of poisoning with toxic glycol based brake
      fluid are reported who presented with mild metabolic acidosis and acute renal
      failure. As all the cases had presented late, treatment with ethanol was not
      started. All of them were treated successfully with haemodialysis.

PMID- 11971849
TI  - Accidental colchicine overdose. A case report and literature review.
AB  - Colchicine overdose is uncommon but potentially life threatening. It is a safe
      drug when used according to established therapeutic guidelines but causes serious
      systemic effects if ingested in doses that exceed the recommendations. Overdose
      must therefore be recognised early and treated appropriately to optimise the
      outcome. A fatal case of colchicine overdose caused by inappropriate self
      medication is reported and to the best of the authors' knowledge, there has been
      no report of fatal accidental overdose in the United Kingdom. The pharmacology of
      colchicine, the clinical features associated with overdose, and the options for
      treatment are discussed.

PMID- 11971851
TI  - Metal fume fever: a case report and review of the literature.
AB  - Metal fume fever is an acutely noxious inhalation syndrome secondary to metal
      oxide fumes. Despite preventative strategies sporadic cases are likely to
      continue to present to emergency departments.

PMID- 11971852
TI  - Methylene blue: a treatment for severe methaemoglobinaemia secondary to misuse of
      amyl nitrite.

PMID- 11971853
TI  - Avulsion of the triceps tendon.

PMID- 11971854
TI  - Spontaneous haemopneumothorax: are guidelines overdue?
AB  - Spontaneous life threatening haemopneumothorax is an unusual but treatable cause
      of unexpected circulatory collapse in young patients. Two case histories are
      presented to illustrate the management of this condition. Diagnosis and initial
      management depends on early recognition of the clinical pattern by accident and
      emergency (A&E) staff and/or hospital physicians. Problems may arise for two
      reasons. Firstly, as the incidence of life threatening spontaneous
      haemopneumothorax is low, admitting medical staff may not have experienced this
      condition in the absence of trauma. Secondly, unlike surgeons, staff in these
      specialties are unlikely to have received training of either traumatic or
      spontaneous haemopneumothorax. The cases illustrate potential problems. Not only
      early recognition of the clinical pattern but also proactive intervention in the
      A&E department are necessary before referral to a cardiothoracic surgeon.
      Furthermore, we suggest treatment would be improved by the introduction of
      management guidelines.

PMID- 11971855
TI  - A rare case of a pedunculated lipoma in the pharynx.
AB  - While lipomas on the trunk and limbs are common, they are rare in the upper
      aerodigestive tract. A case is reported of an 18 cm long pedunculated lipoma
      arising from the hypopharynx in a 73 year old man. The tumour was asymptomatic
      until it appeared in the mouth of the patient after a coughing episode.

PMID- 11971856
TI  - Indicators of mortality from meningococcal disease.

PMID- 11971857
TI  - Hyaluronan promotes the malignant phenotype.
AB  - Hyaluronan is a high-molecular-weight, negatively charged polysaccharide with
      unusual physical and interactive properties. Hyaluronan is localized in the
      extracellular matrix, at the cell surface, and inside cells. Its tissue
      distribution is ubiquitous, but it is particularly concentrated in pericellular
      matrices surrounding proliferating and migrating cells. Hyaluronan contributes to
      cell behavior in at least three ways. Its unique physical properties influence
      the biomechanical properties of extracellular and pericellular matrices; it is a
      template for assembly of other pericellular macromolecules; and it interacts
      directly with cell surface receptors that transduce intracellular signals.
      Experimental studies in animal models have documented a crucial role for
      hyaluronan in tumor growth and metastasis. Cellular manipulations have shown that
      hyaluronan promotes anchorage-independent growth and invasiveness, hallmarks of
      the malignant phenotype.

PMID- 11971858
TI  - Transfection of glucosylceramide synthase antisense inhibits mouse melanoma
      formation.
AB  - MEB4 murine melanoma cells synthesize G(M3) as the major ganglioside. Inhibition
      of G(M3) synthesis by a specific glucosylceramide synthase inhibitor resulted in
      reduced tumorigenicity and metastatic potential of these cells. We used a
      molecular approach--antisense transfection targeting the glucosylceramide
      synthase gene--to regulate glycosphingolipid synthesis by MEB4 cells and examine
      the influence on tumor formation. Antisense transfection inhibited the synthesis
      of the direct product of glucosylceramide synthase, glucosylceramide, and
      consequently G(M3) ganglioside, by MEB4 cells, reducing the concentration of
      G(M3) in the transfectants by up to 58%. Although neither morphology nor
      proliferation kinetics of the cultured cells was affected, the inhibition of
      glycosphingolipid synthesis and reduction of total ganglioside content caused a
      striking reduction in melanoma formation in mice. Only 1/60 (2%) of mice injected
      ID with 10(4) antisense-transfected MA173 cells formed a tumor, compared to 31/60
      (52%) of mice receiving MEB4 cells and 7/15 (47%) of mice receiving the MS2 sense
      transfected cells (p < 0.001 and p = 0.005, respectively). These findings
      demonstrate that stable transfection of glucosylceramide synthase antisense
      reduces cellular glycosphingolipid levels and reduces tumorigenicity, providing
      further experimental support for an enhancing role of gangliosides in tumor
      formation.

PMID- 11971859
TI  - Biosynthesis of the carbohydrate antigenic determinants, Globo H, blood group H,
      and Lewis b: a role for prostate cancer cell alpha1,2-L-fucosyltransferase.
AB  - Prostate carcinoma LNCaP cells were unique among several human cancer cell lines
      which include two other prostate cancer cell lines, PC-3 and DU-145, in
      expressing alpha1,2-L-fucosyltransferase (FT) as an exclusive FT activity.
      Affinity gel-GDP and Sephacryl S100 HR columns were used for a partial
      purification of this enzyme from 3.9 x 10(9) LNCaP cells (approximately 200-fold;
      40% yield). The K(m) value (2.7 mM) for the LacNAc type 2 acceptor was quite
      similar to the one reported for the cloned blood group H gene-specified alpha1,2
      FT [Chandrasekaran et al. (1996) Biochemistry 35, 8914-8924]. N-Ethylmaleimide
      was a potent inhibitor (K(i ) 12.5 microM). The enzyme showed four-fold acceptor
      preference for the LacNAc type 2 unit in comparison to the T-hapten in mucin core
      2 structure. Its main features were similar to those of the cloned enzyme: (1) C
      6 sulfation of terminal Gal in the LacNAc unit increased the acceptor efficiency,
      whereas C-6 sialylation abolished acceptor ability; (2) C-6 sulfation of GlcNAc
      in LacNAc type 2 decreased by 80% the acceptor ability, whereas LacNAc type 1 was
      unaffected; (3) Lewis x did not serve as an acceptor; (4) the C-4 hydroxyl rather
      than the C-6 hydroxyl group of the GlcNAc moiety in LacNAc type1 was essential
      for activity; and (5) the acrylamide copolymer of Galbeta1,3GlcNAcbeta-O-Al was
      the best acceptor among the acrylamide copolymers. Additionally, highly
      significant biological features of alpha1,2FT were identified in the present
      study. The synthesis of Globo H and Lewis b determinants became evident from the
      fact that Galbeta1,3GalNAcbeta1,3Galalpha-O-Me and Galbeta1,3(Fucalpha1,4)Glc
      NAcbeta1,3Galbeta-O-Me served as high-affinity acceptors for this enzyme.
      Further, D-Fucbeta1,3Gal-NAcbeta1,3Galalpha-O-Me was a very efficient acceptor,
      indicating that the C-6 hydroxyl group of the terminal Gal moiety in Globo H is
      not essential for the enzyme activity. Thus, the present study was able to
      demonstrate three different catalytic roles of LNCaP alpha1,2-FT, namely, the
      expressions of blood group H, Lewis b from Lewis a, and Globo H.

PMID- 11971860
TI  - Purification and cDNA cloning of Xenopus liver galectins and their expression.
AB  - We have characterized galectin family proteins in adult tissues of Xenopus laevis
      and purified 14-kDa and 36-kDa proteins from the liver. The liver galectins
      showed comparable hemagglutination activities to those of mammalian galectins.
      Furthermore, we isolated five galectin cDNAs from a Xenopus liver library. These
      cDNAs revealed that X. laevis galectins (xgalectins) form a family consisting of
      at least proto and tandem repeat types based on their domain structures, like the
      mammalian galectin family. Two proto-type xgalectins, -Ia and -Ib, exhibited a
      high sequence identity (91%) with each other at the amino acid level and were
      most similar (49-50% identity) to human galectin-1. From their sequence
      similarity and ubiquitous tissue distributions, xgalectins-Ia and -Ib both seemed
      to be Xenopus homologues of mammalian galectin-1. Three tandem repeat-type
      xgalectins were newly identified. Two of them, xgalectins-IIa and -IIIa, seemed
      to be homologous to human galectins-4 and -9, respectively, judging from their
      high sequence similarities (42-50% identity). However, xgalectin-IVa seemed to be
      a novel type. Distributions of mRNAs of xgalectins were analyzed by northern
      hybridization. In addition to adult tissues, either of three tandem repeat-type
      xgalectins were expressed in whole embryos. Moreover, amino acid sequence
      analysis of liver proteins indicated that xgalectins-Ia, -IIa, and -IIIa are
      produced as abundant galectins in the adult liver.

PMID- 11971861
TI  - Absorption of anti-blood group A antibodies on P-selectin glycoprotein ligand
      1/immunoglobulin chimeras carrying blood group A determinants: core saccharide
      chain specificity of the Se and H gene encoded alpha1,2 fucosyltransferases in
      different host cells.
AB  - To specifically eliminate recipient anti-blood group ABO antibodies prior to ABO
      incompatible organ or bone marrow transplantation, an efficient absorber of ABO
      antibodies has been developed in which blood group determinants may be carried at
      high density and by different core saccharide chains on a mucin-type protein
      backbone. The absorber was made by transfecting different host cells with cDNAs
      encoding a P-selectin glycoprotein ligand-1/mouse immunoglobulin G(2b) chimera
      (PSGL-1/mIgG(2b)), the H- or Se-gene encoded alpha1,2-fucosyltransferases (FUT1
      or FUT2) and the blood group A gene encoded alpha1,3 N
      acetylgalactosaminyltransferase (alpha1,3 GalNAcT). Western blot analysis of
      affinity-purified recombinant PSGL-1/mIgG(2b) revealed that different precursor
      chains were produced in 293T, COS-7m6, and Chinese hamster ovary (CHO)-K1 host
      cells coexpressing FUT1 or FUT2. FUT1 directed expression of H type 2 structures
      mainly, whereas FUT2 preferentially made H type 3 structures. None of the host
      cells expressing either FUT1 or FUT2 supported expression of H type 1 structures.
      Furthermore, the highest A epitope density was on PSGL-1/mIgG2(2b) made in CHO-K1
      cells coexpressing FUT2 and the alpha1,3 GalNAcT. This PSGL-1/mIgG(2b) was used
      for absorption of anti-blood group A antibodies in human blood group O serum. At
      least 80 times less A trisaccharides on PSGL-1/mIgG(2b) in comparison to A
      trisaccharides covalently linked to macroporous glass beads were needed for the
      same level of antibody absorption. In conclusion, PSGL-1/mIgG(2b), if substituted
      with A epitopes, was shown to be an efficient absorber of anti-blood group A
      antibodies and a suitable model protein for studies on protein glycosylation.

PMID- 11971862
TI  - An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and
      sialidase activities of influenza viruses.
AB  - The compound Neu5Ac3alphaF-DSPE (4), in which the C-3 position was modified with
      an axial fluorine atom, inhibited the catalytic hydrolysis of influenza virus
      sialidase and the binding activity of hemagglutinin. The inhibitory activities to
      sialidases were independent of virus isolates examined. With the positive results
      obtained for inhibition of hemagglutination and hemolysis induced by A/Aichi/2/68
      virus, the inhibitory effect of Neu5Ac3alphaF-DSPE (4) against MDCK cells was
      examined, and it was found that 4 inhibits the viral infection with IC50 value of
      5.6 microM based on the cytopathic effects. The experimental results indicate
      that compound 4 not only inhibits the attachment of virus to the cell surface
      receptor but also disturbs the release of the progeny viruses from infected cells
      by inhibiting both hemagglutinin and sialidase of the influenza viruses. The
      study suggested that the compound is a new class of bifunctional drug candidates
      for the future chemotherapy of influenza.

PMID- 11971863
TI  - Functional analysis of the carbohydrate recognition domains and a linker peptide
      of galectin-9 as to eosinophil chemoattractant activity.
AB  - Human galectin-9 is a beta-galactoside-binding protein consisting of two
      carbohydrate recognition domains (CRDs) and a linker peptide. We have shown that
      galectin-9 represents a novel class of eosinophil chemoattractants (ECAs)
      produced by activated T cells. A previous study demonstrated that the
      carbohydrate binding activity of galectin-9 is indispensable for eosinophil
      chemoattraction and that the N- and C-terminal CRDs exhibit comparable ECA
      activity, which is substantially lower than that of full-length galectin-9. In
      this study, we investigated the roles of the two CRDs in ECA activity in
      conjunction with the sugar-binding properties of the CRDs. In addition, to
      address the significance of the linker peptide structure, we compare the three
      isoforms of galectin-9, which only differ in the linker peptide region, in terms
      of ECA activity. Recombinant proteins consisting of two N-terminal CRDs (galectin
      9NN), two C-terminal CRDs (galectin-9CC), and three isoforms of galectin-9
      (galectin-9S, -9M, and -9L) were generated. All the recombinant proteins had
      hemagglutination activity comparable to that of the predominant wild-type
      galectin-9 (galectin-9M). Galectin-9NN and galectin-9CC induced eosinophil
      chemotaxis in a manner indistinguishable from the case of galectin-9M. Although
      the isoform of galectin-9 with the longest linker peptide, galectin-9L, exhibited
      limited solubility, the three isoforms showed comparable ECA activity over the
      concentration range tested. The interactions between N- and C-terminal CRDs and
      glycoprotein glycans and glycolipid glycans were examined using frontal affinity
      chromatography. Both CRDs exhibited high affinity for branched complex type sugar
      chain, especially for tri- and tetraantennary N-linked glycans with N
      acetyllactosamine units, and the oligosaccharides inhibited the ECA activity at
      low concentrations. These results suggest that the N- and C-terminal CRDs of
      galectin-9 interact with the same or a closely related ligand on the eosinophil
      membrane when acting as an ECA and that ECA activity does not depend on a
      specific structure of the linker peptide.

PMID- 11971864
TI  - High-affinity binding of recombinant human galectin-4 to SO(3)(-)-->3Galbeta1-
      >3GalNAc pyranoside.
AB  - Galectin-4 is a member of galectin family and has two carbohydrate recognition
      domains. Although galectin-4 has been thought to function in cell adhesion, its
      precise carbohydrate binding specificity has not yet been clarified. We studied
      the carbohydrate binding specificity of galectin-4 comparatively with that of
      galectin-3, using surface plasmon resonance, galectin-3- or -4-Sepharose column
      chromatography and the inhibition assay of their binding to immobilized
      asialofetuin. Galectin-3 broadly recognized lactose, type 1, type 2, and core 1.
      The substitution at the C-2 and C-3 position of beta-galactose in these
      oligosaccharides with alpha-fucose, alpha-GalNAc, alpha-Neu5Ac, or sulfate
      increased the binding ability for galectin-3, whereas the substitution at the C-4
      or C-6 position diminished the affinity. In contrast, galectin-4 had quite weak
      affinity to lactose, type 1, and type 2 (K(d) congruent with 8 x 10(-4) M).
      Galectin-4 showed weak binding ability to core 1 and C-2' or -3'-substituted
      lactose, type 1, and type 2 with alpha-fucose, alpha-GalNAc, or sulfate (K(d) : 5
      x 10(-5) approximately 3 x 10(-4) M). Interestingly, the K(d) value, 3.4 x 10(-6)
      M, of SO(3)(-)-->3Galbeta1-->3GalNAc-O-Bn to galectin-4 at 25 degrees C was two
      orders of magnitude lower than that of core 1-O-Bn. 3'-Sialylated core 1 had very
      weak affinity to galectin-4, suggesting that 3'-O-sulfation of core 1 is critical
      for the recognition. These results suggest that galectin-4 has a unique
      carbohydrate binding specificity and interacts with O-linked sulfoglycans.

PMID- 11971865
TI  - Lymph node macrophages, but not spleen macrophages, express high levels of
      unmasked sialoadhesin: implication for the adhesive properties of macrophages in
      vivo.
AB  - Sialoadhesin is a macrophage-restricted adhesion molecule that recognizes N
      acetylneuraminylalpha2-3galactose structure. We prepared a multivalent
      neoglycoprotein probe carrying this oligosaccharide and characterized the binding
      activity of sialoadhesin on native rat macrophages. Macrophages from mesenteric
      and axillar lymph nodes exhibited 36-fold higher activity than those from the
      spleen. The K(d) values of the probe binding to macrophages of the two organs
      were indistinguishable (1-2 nM), whereas the B(max) value of lymph node
      macrophages was markedly higher than that of splenic macrophages. Western blot
      analysis revealed that the quantity of sialoadhesin present in lymph node
      macrophages was 25-fold higher than in splenic macrophages. High cell surface
      expression of sialoadhesin on lymph node macrophages was also shown by flow
      cytometry. To examine the "masking" of sialoadhesin by endogenous
      sialoglycoconjugates, we treated macrophages with sialidase before measuring the
      probe binding. After sialidase treatment, the binding activity of splenic
      macrophages increased fourfold, whereas that of lymph node macrophages did not
      increase. In conclusion, we have identified macrophages expressing high levels of
      unmasked sialoadhesin in lymph nodes. The unmasked forms on these macrophages are
      available for sialoadhesin-dependent adhesive functions, unlike the masked forms
      on the majority of splenic macrophages.

PMID- 11971866
TI  - Several polylactosamine-modifying glycosyltransferases also use internal
      GalNAcbeta1-4GlcNAc units of synthetic saccharides as acceptors.
AB  - The GalNAcbeta1-4GlcNAc determinant (LdN) occurs in some human and bovine
      glycoconjugates and also in lower vertebrates and invertebrates. It has been
      found in unsubstituted as well as terminally substituted forms at the distal end
      of conjugated glycans, but it has not been reported previously at truly internal
      positions of polylactosamine chains. Here, we describe enzyme-assisted conversion
      of LdNbeta1-OR oligosaccharides into GlcNAcbeta1-3GalNAcbeta1-4GlcNAcbeta1-OR.
      The extension reactions, catalyzed by human serum, were modeled after analogous
      beta3-GlcNAc transfer processes that generate GlcNAcbeta1-3Galbeta1-4GlcNAcbeta1
      OR. The newly synthesized GlcNAcbeta1-3GalNAc linkages were unambiguously
      identified by nuclear magnetic resonance data, including the appropriate long
      range correlations in heteronuclear multiple bond correlation spectra. The novel
      GlcNAcbeta1-3'LdN determinant proved to be a functional acceptor for several
      mammalian glycosyltransferases, suggesting that human polylactosamines may
      contain internal LdN units in many distinct forms. The GlcNAcbeta1-3'LdN
      determinant was unusually resistant toward jackbean beta-N-acetylhexosaminidase;
      the slow degradation should lead to a convenient method for the search of
      putative internal LdN determinants in natural polylactosamine chains.

PMID- 11971867
TI  - Overexpression, purification, and partial characterization of Saccharomyces
      cerevisiae processing alpha glucosidase I.
AB  - The gene encoding yeast processing alpha glucosidase I, CWH41, was overexpressed
      in Saccharomyces cerevisiae AH22, resulting in a 28-fold increase in expression
      of the soluble form of the enzyme. The soluble enzyme results from proteolytic
      cleavage between residues Ala 24 and Thr 25 of the transmembrane sequence of the
      membrane-bound form of the enzyme. This cleavage could be partially inhibited by
      addition of leupeptin and pepstatin during the enzyme isolation. The enzyme was
      purified to a final specific activity of 8550 U/mg protein using a combination of
      ammonium sulfate precipitation, anion exchange, concanavalin A, and gel
      filtration chromatography. The soluble form of the enzyme is a monomer with a
      molecular weight of 98 kDa by SDS-PAGE, and 89 kDa by gel filtration. The
      molecular weight decreased by approximately 5 kDa after treatment with N
      glycosidase F, indicating that it is a glycoprotein. Soluble glucosidase I was
      sensitive to diethyl pyrocarbonate and not affected by N-ethylmaleimide,
      suggesting that mechanistically it is more similar to the plant than the
      mammalian form of the enzyme.

PMID- 11971868
TI  - Gene expression profiles of poor-prognosis primary breast cancer correlate with
      survival.
AB  - The extensive heterogeneity of breast cancer complicates the precise assessment
      of tumour aggressiveness, making therapeutic decisions difficult and treatments
      inappropriate in some cases. Consequently, the long-term metastasis-free survival
      rate of patients receiving adjuvant chemotherapy is only 60%. There is a genuine
      need to identify parameters that might accurately predict the effectiveness of
      this treatment for each patient. Using cDNA arrays, we profiled tumour samples
      from 55 women with poor-prognosis breast cancer treated with adjuvant
      anthracycline-based chemotherapy. Gene expression monitoring was applied to a set
      of about 1000 candidate cancer genes. Differences in expression profiles provided
      molecular evidence of the clinical heterogeneity of disease. First, we confirmed
      the capacity of a 23-gene predictor set, identified in a previous study, to
      distinguish between tumours associated with different survival. Second, using a
      refined gene set derived from the previous one, we distinguished, among the 55
      clinically homogeneous tumours, three classes with significantly different
      clinical outcome: 5-year overall survival and metastasis-free survival rates were
      respectively 100% and 75% in the first class, 65% and 56% in the second and 40%
      and 20% in the third. This discrimination resulted from the differential
      expression of two clusters of genes encoding proteins with diverse functions,
      including the estrogen receptor (ER). Another finding was the identification of
      two ER-positive tumour subgroups with different survival. These results indicate
      that gene expression profiling can predict clinical outcome and lead to a more
      precise classification of breast tumours. Furthermore, the characterization of
      discriminator genes might accelerate the development of new specific and
      alternative therapies, allowing more rationally tailored treatments that are
      potentially more efficient and less toxic.

PMID- 11971869
TI  - Functional analysis of cone-rod homeobox (CRX) mutations associated with retinal
      dystrophy.
AB  - Mutations in the photoreceptor transcription factor cone-rod homeobox (CRX) have
      been identified in patients with several forms of retinal degenerative disease.
      To investigate the mechanisms by which these mutations cause photoreceptor
      degeneration, CRX constructs representing eleven known mutations, as well as a
      set of C-terminal deletions, were generated and tested for their ability to
      activate a rhodopsin-luciferase reporter in a transient cell transfection assay.
      To further define functional domains, several Gal4dbd-Crx fusions were similarly
      tested using a Gal4 response element containing heterologous promoter. This
      analysis demonstrated that the C-terminal region, between amino acids 200 and
      284, is essential for CRX-mediated transcriptional activation. Consistent with
      this, four mutants carrying C-terminal truncations demonstrated significantly
      reduced transcriptional activation. Confirming the importance of the homeodomain
      (HD), four of the five mutants carrying HD missense mutations displayed altered
      transactivating activity, either decreased (three) or increased (one). In vitro
      protein-DNA binding assays (EMSAs) with CRX-HD peptides representing the three HD
      mutants with decreased transactivating activity, indicated that the alteration
      was due to reduced, but not abolished, DNA binding to CRX targets. Taken
      together, these results support the hypothesis that CRX mutations involved in
      human photoreceptor degeneration act by impairing CRX-mediated transcriptional
      regulation of the photoreceptor genes. However, a clear relationship between the
      magnitude of biochemical abnormality and degree of disease severity was not
      observed, suggesting that other genetic and environmental modifiers may also
      contribute to the disease phenotype.

PMID- 11971870
TI  - Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein.
AB  - The Finnish variant late infantile neuronal ceroid lipofuscinosis (vLINCL)
      belongs to the neuronal ceroid lipofuscinosis group of common recessively
      inherited neurodegenerative disorders. The CLN 5 gene responsible for this brain
      disorder codes for a novel protein with no homology to previously reported
      proteins. In this study, we have investigated the biosynthesis and intracellular
      localization of this protein in transiently transfected BHK-21 cells using a CLN5
      specific peptide antibody. Confocal immunofluorescence microscopy showed that
      wild-type CLN5 is predominantly targeted to lysosomes and immunoprecipitation
      analysis recognized a 60 kDa polypeptide. The molecular weight of this protein
      was reduced to 40 kDa by deglycosylation with Endo H and to 38 kDa with PNGase F.
      The same-sized glycosylated polypeptides were also observed in the media,
      suggesting that the 60 kDa glycosylated CLN5 polypeptide represents a soluble
      lysosomal glycoprotein, not an integral transmembrane protein as predicted
      earlier. The most common human vLINCL mutation blocked the lysosomal targeting of
      expressed polypeptides. This would imply that the pathogenesis of vLINCL would be
      associated with the defective lysosomal trafficking, preventing the normal
      biological function of the corresponding polypeptide.

PMID- 11971871
TI  - Activation of the beta-like globin genes in transgenic mice is dependent on the
      presence of the beta-locus control region.
AB  - The beta-globin locus control region (LCR) is a powerful regulatory element
      required for high-level globin gene expression. We have generated transgenic
      mouse lines carrying a beta-globin locus yeast artificial chromosome lacking the
      LCR to determine if the LCR is required for globin gene activation. beta-Globin
      gene expression was analyzed by RNase protection, but no detectable levels of
      epsilon-, gamma- and beta-globin gene transcripts were produced at any stage of
      development. These findings suggest that the presence of the LCR is a minimum
      requirement for globin gene expression. Next, we tested whether the LCR is
      necessary to activate globin gene expression in a gamma-globin promoter mutant
      that causes hereditary persistence of fetal hemoglobin (HPFH). beta-YAC
      transgenic mice carrying the -117 HPFH mutation and a HS3 core deletion that
      specifically abolishes gamma-globin gene expression during definitive
      erythropoiesis were produced to test whether the -117 (A)gamma promoter is
      activated in the absence of interaction with the LCR. In four transgenic mouse
      lines, gamma-globin gene expression was absent in adult erythrocytes, suggesting
      that an interaction between the gamma-globin gene promoter and the LCR is
      required for gamma gene activation even when the promoter contains an HPFH
      mutation.

PMID- 11971872
TI  - Huntingtin inclusions do not deplete polyglutamine-containing transcription
      factors in HD mice.
AB  - A pathological hallmark of polyglutamine diseases is the presence of inclusions
      or aggregates of the expanded polyglutamine protein. Polyglutamine inclusions are
      present in the neuronal nucleus in a number of inherited neurodegenerative
      disorders, including Huntington disease (HD). Recent studies suggest that
      polyglutamine inclusions may sequester polyglutamine-containing transcription
      factors and deplete their concentration in the nucleus, leading to altered gene
      expression. To test this hypothesis, we examined the expression and localization
      of the polyglutamine-containing or glutamine-rich transcription factors TBP, CBP
      and Sp1 in HD mouse models. All three transcription factors were diffusely
      distributed in the nucleus, despite the presence of abundant intranuclear
      inclusions. There were no differences in the nuclear staining of these
      transcription factors between HD and wild-type mouse brains. Although some CBP
      staining appeared as dots in the selective brain regions (e.g. hypothalamus and
      amygdala), double labeling showed that most CBP was not co-localized with
      huntingtin nuclear inclusions. Electron microscopy confirmed that CBP was
      diffusely distributed in the nucleus. Western blots showed that these
      transcription factors were not trapped in huntingtin inclusions. In the striatum
      of HD mice, which suffers a significant reduction in the expression of a number
      of genes, mutant huntingtin was present in both an aggregated and a diffuse form.
      These findings suggest that altered gene expression may result from the
      interactions of soluble mutant huntingtin with nuclear transcription factors,
      rather than from the depletion of transcription factors by nuclear inclusions.

PMID- 11971873
TI  - Tbx1 mutation causes multiple cardiovascular defects and disrupts neural crest
      and cranial nerve migratory pathways.
AB  - TBX1 is the major candidate gene for DiGeorge syndrome (DGS). Mouse studies have
      shown that the Tbx1 gene is haploinsufficient, as expected for a DGS candidate
      gene, and that it is required for the development of pharyngeal arches and
      pouches, as predicted by the DGS clinical phenotype. However, a detailed analysis
      of the cardiovascular phenotype associated with Tbx1 mutations has not been
      reported. Here we show that Tbx1 deficiency causes a number of distinct vascular
      and heart defects, suggesting multiple roles in cardiovascular development -
      specifically formation and growth of the pharyngeal arch arteries, growth and
      septation of the outflow tract of the heart, interventricular septation, and
      conal alignment. Comparison of phenotype and gene expression using a Tbx1-lacZ
      reporter allele supports a cell-autonomous function in the growth of the
      pharyngeal apparatus, and a cell non-autonomous function in the growth and early
      remodeling of the pharyngeal arch arteries. Our data do not support a direct role
      of neural crest cells in the pathogenesis of the Tbx1 mutant phenotype; however,
      these cells, and the cranial nerves, are misdirected. We hypothesize that this is
      due to the lack of a guidance role from the pouch endoderm, which is missing in
      these mutants.

PMID- 11971874
TI  - Functional polycystin-1 expression is developmentally regulated during epithelial
      morphogenesis in vitro: downregulation and loss of membrane localization during
      cystogenesis.
AB  - Polycystin-1 is a protein mutated in the majority of cases of autosomal dominant
      polycystic kidney disease (ADPKD), but its role in the molecular pathway of
      tubulogenesis and cystogenesis is not understood. To define the role of
      polycystin-1 during dynamic changes in formation of intercellular contacts and
      cell polarity accompanying epithelial morphogenesis, we have utilized a 3D MDCK
      in vitro model of tubulogenesis and cystogenesis. Here we demonstrate that
      polycystin-1 is a novel component of desmosomal junctions of epithelial cells. A
      striking downregulation of polycystin-1 mRNA was detected in cysts as compared to
      tubules, leading to altered protein expression and localization. While polycystin
      1 is localized to basolateral membranes of MDCK tubules, it is only detected in
      cytoplasmic pools in cystic cells. Furthermore, the expression of polycystin-1 is
      modulated during distinct stages of HGF-induced tubulogenesis from MDCK cysts.
      Thus, polycystin-1 is not detected in intercellular contacts at early steps of
      tubulogenesis, but assumes its basolateral localization at the time of cell
      polarization and lumen formation. An important role of polycystin-1 is further
      demonstrated using the pancreatic ductal epithelial cell line SU.86.86 which
      undergoes in vitro differentiation resulting in the formation of domes. Dome
      formation is thought to parallel tubular differentiation and morphogenesis in
      vivo. Our data reveal significant upregulation of polycystin-1 mRNA and protein
      levels in domes. Collectively, our results demonstrate a critical importance of
      controlled level of polycystin-1 expression for proper tubular differentiation
      and maturation. We suggest that the loss of polycystin-1 from its basolateral
      location in tubular epithelium may alter critical pathways controlling normal
      tubulogenesis leading to cystic transformation.

PMID- 11971875
TI  - PLUNC: a novel family of candidate host defence proteins expressed in the upper
      airways and nasopharynx.
AB  - The upper respiratory tract, including the nasal and oral cavities, is the major
      route of entry of pathogens into the body, and early recognition of bacterial
      products in this region is critical for host defence. A well-established family
      of four proteins involved in this process are bactericidal/permeability
      increasing protein (BPI) and lipopolysaccharide-binding protein (LBP), which are
      central to the host defence against bacteria, and cholesteryl ester transfer
      protein (CETP) and phospholipid transfer protein (PLTP), which have also been
      implicated in this response. In this paper, we demonstrate the existence of a
      related family of seven human proteins, which we designate PLUNC proteins. The
      PLUNC proteins are encoded by adjacent genes found within a 300 kb region of
      chromosome 20, suggesting that they may be under transcriptional control of
      shared genomic elements, and expression data shows that these proteins are found
      in overlapping regions of the pulmonary, nasopharyngeal and oral epithelium,
      sites where the previously described BPI family members are not expressed.
      Whereas the BPI family are predicted to share very closely similar three
      dimensional structures, the PLUNC family is predicted to have much greater
      variability in the N-terminal domain, corresponding to the active domain of BPI,
      thus creating the notion of a BPI/PLUNC structural superfamily. We suggest that
      members of the PLUNC family may function in the innate immune response in regions
      of the mouth, nose and lungs, which are sites of significant bacterial exposure.

PMID- 11971876
TI  - Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in
      postnatal death due to depressed feeding behavior.
AB  - HAP-1 is a huntingtin-associated protein that is enriched in the brain. To gain
      insight into the normal physiological role of HAP-1, mice were generated with
      homozygous disruption at the Hap1 locus. Loss of HAP-1 expression did not alter
      the gross brain expression levels of its interacting partners, huntingtin and
      p150glued. Newborn Hap1(-/-) animals are observed at the expected Mendelian
      frequency suggesting a non-essential role of HAP-1 during embryogenesis.
      Postnatally, Hap1(-/-) pups show decreased feeding behavior that ultimately leads
      to malnutrition, dehydration and premature death. Seventy percent of Hap1(-/-)
      pups fail to survive past the second postnatal day (P2) and 100% of Hap1(-/-)
      pups fail to survive past P9. From P2 until death, Hap1(-/-) pups show markedly
      decreased amounts of ingested milk. Hap1(-/-) pups that survive to P8 show signs
      of starvation including greatly decreased serum leptin levels, decreased brain
      weight and atrophy of the brain cortical mantel. HAP-1 is particularly enriched
      in the hypothalamus, which is well documented to regulate feeding behavior. Our
      results demonstrate that HAP-1 plays an essential role in regulating postnatal
      feeding.

PMID- 11971877
TI  - Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA
      syndrome, an autoinflammatory disorder.
AB  - PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM
      #604416) and familial recurrent arthritis (FRA) are rare inherited disorders of
      early onset, primarily affecting skin and joint tissues. Recurring inflammatory
      episodes lead to accumulation of sterile, pyogenic, neutrophil-rich material
      within the affected joints, ultimately resulting in significant destruction. We
      recently localized the genes for PAPA syndrome and FRA to chromosome 15q and
      suggested that they are the same disorder. We have now established this by the
      identification of co-segregating disease-causing mutations in the CD2-binding
      protein 1 (CD2BP1; GenBank accession no XM 044569) gene in the two reported
      families with this disorder. E250Q or A230T amino acid substitutions occur within
      a domain highly homologous to yeast cleavage furrow-associated protein CDC15.
      CD2BP1 and its murine ortholog, proline-serine-threonine phosphatase interacting
      protein (PSTPIP1), are adaptor proteins known to interact with PEST-type protein
      tyrosine phosphatases (PTP). Yeast two-hybrid assays demonstrate severely reduced
      binding between PTP PEST and both the E250Q and A230T mutant proteins. Previous
      evidence supports the integral role of CD2BP1 and its interacting proteins in
      actin reorganization during cytoskeletal-mediated events. We hypothesize that the
      disease-causing mutations that we have identified compromise physiologic
      signaling necessary for the maintenance of proper inflammatory response.
      Accordingly we suggest classification of PAPA syndrome as an autoinflammatory
      disease. This CD2BP1-mediated biochemical pathway(s) may function in common
      inflammatory disorders with apparent etiological overlap, such as rheumatoid
      arthritis and inflammatory bowel disease.

PMID- 11971878
TI  - Mutations in TITF-1 are associated with benign hereditary chorea.
AB  - Benign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement
      disorder. The early onset of symptoms (usually before the age of 5 years) and the
      observation that in some BHC families the symptoms tend to decrease in adulthood
      suggests that the disorder results from a developmental disturbance of the brain.
      In contrast to Huntington disease (MIM 143100), BHC is non-progressive and
      patients have normal or slightly below normal intelligence. There is considerable
      inter- and intrafamilial variability, including dysarthria, axial dystonia and
      gait disturbances. Previously, we identified a locus for BHC on chromosome 14 and
      subsequently identified additional independent families linked to the same locus.
      Recombination analysis of all chromosome 14-linked families resulted initially in
      a reduction of the critical interval for the BHC gene to 8.4 cM between markers
      D14S49 and D14S278. More detailed analysis of the critical region in a small BHC
      family revealed a de novo deletion of 1.2 Mb harboring the TITF-1 gene, a
      homeodomain-containing transcription factor essential for the organogenesis of
      the lung, thyroid and the basal ganglia. Here we report evidence that mutations
      in TITF-1 are associated with BHC.

PMID- 11971879
TI  - ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is
      mutated in X-linked mental retardation.
AB  - Investigation of a critical region for an X-linked mental retardation (XLMR)
      locus led us to identify a novel Aristaless related homeobox gene (ARX ).
      Inherited and de novo ARX mutations, including missense mutations and in frame
      duplications/insertions leading to expansions of polyalanine tracts in ARX, were
      found in nine familial and one sporadic case of MR. In contrast to other genes
      involved in XLMR, ARX expression is specific to the telencephalon and ventral
      thalamus. Notably there is an absence of expression in the cerebellum throughout
      development and also in adult. The absence of detectable brain malformations in
      patients suggests that ARX may have an essential role, in mature neurons,
      required for the development of cognitive abilities.

PMID- 11971880
TI  - Does national regulatory mandate of provider order entry portend greater benefit
      than risk for health care delivery? The 2001 ACMI debate. The American College of
      Medical Informatics.
AB  - The 2001 debate of the American College of Medical Informatics focused on the
      proposition that national regulatory mandate of computer-based provider order
      entry (CPOE), to take effect by the end of 2005, portends greater benefit than
      risk for health care delivery. Both sides accepted that provider order entry
      offers potential benefit. Those supporting the proposition emphasized public
      safety, noting that payers have little economic incentive to pay for quality and
      that a mandate would force vendors to improve the usability and value of their
      systems. They argued that the mandate would align the economic incentives to
      finally allow CPOE to be widely adopted. Those opposing the proposition
      emphasized the risks resulting from a mandate, including the direct
      implementation costs, the logistic issues of implementation, and the cost of
      failed implementations. They also noted the potential for errors introduced by
      the systems themselves and the fact that the safety and utility of commercially
      available CPOE products have yet to be proved.

PMID- 11971881
TI  - Desiderata for personal electronic communication in clinical systems.
AB  - Electronic communication among clinicians and patients is becoming an essential
      part of medical practice. Evaluation and selection of these electronic systems,
      called personal clinical electronic communication (PCEC) systems, can be a
      difficult task in institutions that have no prior experience with such systems.
      It is particularly difficult in the clinical context. To directly address this
      point, the authors consulted a group of potential users affiliated with a
      nationally recognized telemedicine project, to determine important
      characteristics of a hypothetical PCEC system. They compiled a list of these
      characteristics and produced a desiderata, or list of desired features, for PCEC
      systems. Two conventional e-mail implementations and three Web-based PCEC systems
      were evaluated with respect to the features. The Web-based systems all scored
      higher than conventional e-mail. It is the hope of the authors that this paper
      will initiate further discussions about the features of PCEC systems and how to
      evaluate them.

PMID- 11971882
TI  - Real-time notification of laboratory data requested by users through alphanumeric
      pagers.
AB  - The authors developed a novel feature in their clinical information systems,
      which allows clinicians to request notification about laboratory results.
      Clinicians who are expecting a particular laboratory result for a particular
      patient can request a report of the result via an alphanumeric pager as soon as
      the result is filed into the patient database. This feature has gained popularity
      and is heavily used in both inpatient and outpatient settings, at a rate of about
      2,300 times per month. This event-monitor-based feature illustrates one way that
      information technology can be applied to improve communication in health care.

PMID- 11971883
TI  - Clinician use of a palmtop drug reference guide.
AB  - OBJECTIVE: Problems involving drug knowledge are one of the most common causes of
      serious medication errors. Although the information that clinicians need is often
      available somewhere, retrieving it expeditiously has been problematic. At the
      same time, clinicians are faced with an ever-expanding pharmacology knowledge
      base. Recently, point-of-care technology has become more widely available and
      more practical with the advent of handheld, or palmtop, computing. Therefore, the
      authors evaluated the clinical contribution of a drug database developed for the
      handheld computer. ePocrates Rx (formerly known as qRx; ePocrates, San Carlos,
      California) is a comprehensive drug information guide that is downloadable free
      from the Internet and designed for the Palm OS platform align="right". DESIGN: A
      seven-day online survey of 3,000 randomly selected ePocrates Rx users was
      conducted during March 2000. MEASUREMENTS: User technology experience, product
      evaluation and usage patterns, and the effects of the drug reference database on
      information-seeking behavior, practice efficiency, decision making, and patient
      care. RESULTS: The survey response rate was 32 percent (n=946). Physicians
      reported that ePocrates Rx saves time during information retrieval, is easily
      incorporated into their usual workflow, and improves drug-related decision
      making. They also felt that it reduced the rate of preventable adverse drug
      events. CONCLUSIONS: Self-reported perceptions by responding clinicians endorse
      improved access to drug information and improved practice efficiency associated
      with the use of handheld devices. The clinical and practical value of using these
      devices in clinical settings will clearly grow further as wireless communication
      becomes more ubiquitous and as more applications become available.

PMID- 11971884
TI  - Design and analysis of controlled trials in naturally clustered environments:
      implications for medical informatics.
AB  - In medical informatics research, study questions frequently involve individuals
      who are grouped into clusters. For example, an intervention may be aimed at a
      clinician (who treats a cluster of patients) with the intention of improving the
      health of individual patients. Correlation among individuals within a cluster can
      lead to incorrect estimates of the sample size required to detect an effect and
      inappropriate estimates of the confidence intervals and the statistical
      significance of the intervention effects. Contamination, which is the spread of
      the effect of an intervention or control treatment to the opposite group, often
      occurs between individuals within clusters. It leads to an attenuation of the
      effect of the intervention and reduced power to detect a difference. If
      individuals are randomized in a clinical trial (individual-randomized trial),
      then correlation must be taken into account in the analysis, and the sample size
      may need to be increased to compensate for contamination. Randomizing clusters
      rather than individuals (cluster-randomized trials) can eliminate contamination
      and may be preferred for logistical reasons. Cluster-randomized trials are
      generally less efficient than individual-randomized trials, so the tradeoffs must
      be assessed. Correlation must be taken into account in the analysis and in the
      sample-size calculations for cluster-randomized trials.

PMID- 11971885
TI  - Design and applications of a multimodality image data warehouse framework.
AB  - A comprehensive data warehouse framework is needed, which encompasses imaging and
      non-imaging information in supporting disease management and research. The
      authors propose such a framework, describe general design principles and system
      architecture, and illustrate a multimodality neuroimaging data warehouse system
      implemented for clinical epilepsy research. The data warehouse system is built on
      top of a picture archiving and communication system (PACS) environment and
      applies an iterative object-oriented analysis and design (OOAD) approach and
      recognized data interface and design standards. The implementation is based on a
      Java CORBA (Common Object Request Broker Architecture) and Web-based architecture
      that separates the graphical user interface presentation, data warehouse business
      services, data staging area, and backend source systems into distinct software
      layers. To illustrate the practicality of the data warehouse system, the authors
      describe two distinct biomedical applications--namely, clinical diagnostic workup
      of multimodality neuroimaging cases and research data analysis and decision
      threshold on seizure foci lateralization. The image data warehouse framework can
      be modified and generalized for new application domains.

PMID- 11971886
TI  - The evolution of definitions for nursing informatics: a critical analysis and
      revised definition.
AB  - Despite the fact that nursing informatics is entering its third decade as a
      specialty within nursing, many definitions still exist to describe the field.
      This paper offers a rationale for a definition for nursing informatics and a
      critical analysis of past definitions. An organizing framework of technology
      oriented, conceptual, and role-oriented definitions is used to critique these
      definitions. Subsequently, a revised definition is proposed. This evolutionary
      definition integrates critical concepts from past work and adds components that
      are currently missing--patients, information communication, information
      structures, and decision making. A separate role specification for informatics
      nurse specialists is provided.

PMID- 11971887
TI  - Mapping abbreviations to full forms in biomedical articles.
AB  - OBJECTIVE: To develop methods that automatically map abbreviations to their full
      forms in biomedical articles. METHODS: The authors developed two methods of
      mapping defined and undefined abbreviations (defined abbreviations are paired
      with their full forms in the articles, whereas undefined ones are not). For
      defined abbreviations, they developed a set of pattern-matching rules to map an
      abbreviation to its full form and implemented the rules into a software program,
      AbbRE (for "abbreviation recognition and extraction"). Using the opinions of
      domain experts as a reference standard, they evaluated the recall and precision
      of AbbRE for defined abbreviations in ten biomedical articles randomly selected
      from the ten most frequently cited medical and biological journals. They also
      measured the percentage of undefined abbreviations in the same set of articles,
      and they investigated whether they could map undefined abbreviations to any of
      four public abbreviation databases (GenBank LocusLink, SWISSPROT, LRABR of the
      UMLS Specialist Lexicon, and BioABACUS). RESULTS: AbbRE had an average 0.70
      recall and 0.95 precision for the defined abbreviations. The authors found that
      an average of 25 percent of abbreviations were defined in biomedical articles and
      that of a randomly selected subset of undefined abbreviations, 68 percent could
      be mapped to any of four abbreviation databases. They also found that many
      abbreviations are ambiguous (i.e., they map to more than one full form in
      abbreviation databases). CONCLUSION: AbbRE is efficient for mapping defined
      abbreviations. To couple AbbRE with abbreviation databases for the mapping of
      undefined abbreviations, not only exhaustive abbreviation databases but also a
      method to resolve the ambiguity of abbreviations in the databases are needed.

PMID- 11971888
TI  - Combining geometric and probabilistic reasoning for computer-based penetrating
      trauma assessment.
AB  - OBJECTIVE: To ascertain whether three-dimensional geometric and probabilistic
      reasoning methods can be successfully combined for computer-based assessment of
      conditions arising from ballistic penetrating trauma to the chest and abdomen.
      DESIGN: The authors created a computer system (TraumaSCAN) that integrates three
      dimensional geometric reasoning about anatomic likelihood of injury with
      probabilistic reasoning about injury consequences using Bayesian networks.
      Preliminary evaluation of TraumaSCAN was performed via a retrospective study
      testing performance of the system on data from 26 cases of actual gunshot wounds.
      MEASUREMENTS: Areas under the receiver operating characteristics (ROC) curve were
      calculated for each condition modeled in TraumaSCAN that was present in the 26
      cases. The comprehensiveness and relevance of the TraumaSCAN diagnosis for the 26
      cases were used to assess the overall performance of the system. To test the
      ability of TraumaSCAN to handle limited findings, these measurements were
      calculated both with and without input of observed findings into the Bayesian
      network. RESULTS: For the 11 conditions assessed, the worst area under the ROC
      curve with no observed findings input into the Bayesian network was 0.542 (95%
      CI, 0.146-0.937), the median was 0.883 (95% CI, 0.713-1.000), and the best was
      1.00 (95% CI, 1.000-1.000). The worst area under the ROC curve with all observed
      findings input into the Bayesian network was 0.835 (95% CI, 0.602-1.000), the
      median was 0.941 (95% CI, 0.827-1.000), and the best was 0.992 (95% CI, 0.965
      1.000). A comparison of the areas under the curve obtained with and without input
      of observed findings into the Bayesian network showed that there were significant
      differences for 2 of the 11 conditions assessed. CONCLUSION: A computer-based
      method that combines geometric and probabilistic reasoning shows promise as a
      tool for assessing ballistic penetrating trauma to the chest and abdomen.

PMID- 11971889
TI  - Factors associated with success in searching MEDLINE and applying evidence to
      answer clinical questions.
AB  - OBJECTIVES: This study sought to assess the ability of medical and nurse
      practitioner students to use MEDLINE to obtain evidence for answering clinical
      questions and to identify factors associated with the successful answering of
      questions. METHODS: A convenience sample of medical and nurse practitioner
      students was recruited. After completing instruments measuring demographic
      variables, computer and searching attitudes and experience, and cognitive traits,
      the subjects were given a brief orientation to MEDLINE searching and the
      techniques of evidence-based medicine. The subjects were then given 5 questions
      (from a pool of 20) to answer in two sessions using the Ovid MEDLINE system and
      the Oregon Health & Science University library collection. Each question was
      answered using three possible responses that reflected the quality of the
      evidence. All actions capable of being logged by the Ovid system were captured.
      Statistical analysis was performed using a model based on generalized estimating
      equations. The relevance-based measures of recall and precision were measured by
      defining end queries and having relevance judgments made by physicians who were
      not associated with the study. RESULTS: Forty-five medical and 21 nurse
      practitioner students provided usable answers to 324 questions. The rate of
      correctness increased from 32.3 to 51.6 percent for medical students and from
      31.7 to 34.7 percent for nurse practitioner students. Ability to answer questions
      correctly was most strongly associated with correctness of the answer before
      searching, user experience with MEDLINE features, the evidence-based medicine
      question type, and the spatial visualization score. The spatial visualization
      score showed multi-colinearity with student type (medical vs. nurse
      practitioner). Medical and nurse practitioner students obtained comparable recall
      and precision, neither of which was associated with correctness of the answer.
      CONCLUSIONS: Medical and nurse practitioner students in this study were at best
      moderately successful at answering clinical questions correctly with the
      assistance of literature searching. The results confirm the importance of
      evaluating both search ability and the ability to use the resulting information
      to accomplish a clinical task.

PMID- 11971890
TI  - Providing concept-oriented views for clinical data using a knowledge-based
      system: an evaluation.
AB  - OBJECTIVE: Clinical information systems typically present patient data in
      chronologic order, organized by the source of the information (e.g., laboratory,
      radiology). This study evaluates the functionality and utility of a knowledge
      based system that generates concept-oriented views (organized around clinical
      concepts such as disease or organ system) of clinical data. DESIGN: The authors
      have developed a system that uses a knowledge base of interrelationships between
      medical concepts to infer relationships between data in electronic medical
      records. They use these inferences to produce summaries, or views, of the data
      that are relevant to a specific concept of interest. They evaluated the ability
      of the system to select relevant information, reduce information overload, and
      support physician information retrieval. MEASUREMENTS: The sensitivity and
      specificity of the system for identifying relevant patient information were
      calculated. Effect on information overload was assessed by comparing the amount
      of information in each view with the amount of information in the entire record.
      Information retrieval accuracy and cost (time) were used to measure the effect of
      using concept-oriented views on the efficiency and effectiveness of retrievals.
      RESULTS: The sensitivity and specificity of the system for identifying relevant
      clinical information were generally in the range of 70 to 80 percent. Concept
      oriented views are effective in reducing the amount of information retrieved
      (over 80 percent reduction) and, compared with source-oriented views, are able to
      improve physician retrieval accuracy (p=0.04). CONCLUSION: Computer-generated,
      concept-oriented views can be used to reduce clinician information overload and
      improve the accuracy of clinical data retrieval.

PMID- 11971891
TI  - A discipline by any other name...

PMID- 11971893
TI  - Physician satisfaction with order entry systems.

PMID- 11971895
TI  - Epstein-Barr virus BZLF1 gene is activated by transforming growth factor-beta
      through cooperativity of Smads and c-Jun/c-Fos proteins.
AB  - Induction of Epstein-Barr virus (EBV) production in an EBV-positive cell is
      achieved by expression of the gene BZLF1 that switches the latent state into a
      lytic state. The expression of the BZLF1 gene is initiated from the promoter Zp,
      which is normally suppressed in EBV-transformed B cells. The BZLF1 gene can be
      induced for expression by activating agents, such as transforming growth factor
      beta (TGF-beta) and 12-O-tetradecanoylphorbol-13-acetate. The 12-O
      tetradecanoylphorbol-13-acetate-responsive element located in the Zp is the AP-1
      motif. The TGF-beta-responsive element, however, has not been determined. We
      demonstrated that the Smad4-binding element site, GTCTG, from -233 to -229, was
      located in the regulatory region of the Zp relative to the BZLF1 transcription
      initiation site and was physically associated with Smad4. This association was
      important for the TGF-beta induction of Zp. We also showed from the results of co
      transfection experiments and electrophoretic mobility shift assays that both the
      AP-1 motif and Smad4-binding element site appeared to be required for the TGF
      beta-induced activation of Zp. This effect was mediated through the cooperation
      of Smad3/Smad4 and c-Jun/c-Fos that formed a complex. TGF-beta treatment of Rael
      cells induced production of infectious EBV particles that was capable of
      infecting EBV-negative CA46 cells and transforming normal cord blood B cells, in
      vitro. Those data support a mechanism that TGF-beta induces the latent EBV in
      cells to enter the viral lytic cycle through regulation of key viral proteins by
      TGF-beta signal transducers. Those findings also suggest a role of TGF-beta in
      EBV-associated diseases.

PMID- 11971896
TI  - Impaired protein kinase C activation/translocation in Epstein-Barr virus-infected
      monocytes.
AB  - Infection of human monocytes by Epstein-Barr virus (EBV) has been linked to a
      decrease in the production of proinflammatory mediators as well as an impairment
      of phagocytosis. Considering the key role of protein kinases C (PKCs) in many
      biological functions of monocytes, including phagocytosis, we investigated the
      effects of EBV on the PKC activity in infected monocytes. Our results indicate
      that infection of monocytes by EBV impairs both phorbol 12-myristate 13-acetate
      (PMA)-induced translocation of PKC isozymes alpha and beta from cytosol to
      membrane as well as the PKC enzymatic activity. Similarly, the subcellular
      distribution of the receptor for activated C kinase (RACK), an anchoring protein
      essential to PKC translocation, was also found to be reduced in EBV-infected
      monocytes. Transfection of 293T cells with an expression vector coding for the
      immediate-early protein ZEBRA of EBV resulted in impaired PMA-induced
      translocation and activity of PKC. Using co-immunoprecipitation assays, the ZEBRA
      protein was found to physically interact with the RACK1 protein. Thus interaction
      of ZEBRA with RACK likely results in the inhibition of PKC activity, which in
      turn affects functions of monocytes, such as phagocytosis.

PMID- 11971897
TI  - Activation of c-Raf kinase by ultraviolet light. Regulation by retinoids.
AB  - The present study highlights retinoids as modulators of c-Raf kinase activation
      by UV light. Whereas a number of retinoids, including retinol, 14
      hydroxyretroretinol, anhydroretinol (AR), and retinoic acid bound the c-Raf
      cysteine-rich domain (CRD) with equal affinity in vitro as well as in vivo, they
      displayed different, even opposing, effects on UV-mediated kinase activation;
      retinol and 14-hydroxyretroretinol augmented responses, whereas retinoic acid and
      AR were inhibitory. Oxidation of thiol groups of cysteines by reactive oxygen,
      generated during UV irradiation, was the primary event in c-Raf activation,
      causing the release of zinc ions and, by inference, a change in CRD structure.
      Retinoids modulated these oxidation events directly: retinol enhanced, whereas AR
      suppressed, zinc release, precisely mirroring the retinoid effects on c-Raf
      kinase activation. Oxidation of c-Raf was not sufficient for kinase activation,
      productive interaction with Ras being mandatory. Further, canonical tyrosine
      phosphorylation and the action of phosphatase were essential for optimal c-Raf
      kinase competence. Thus, retinoids bound c-Raf with high affinity, priming the
      molecule for UV/reactive oxygen species-mediated changes of the CRD that set off
      GTP-Ras interaction and, in context with an appropriate phosphorylation pattern,
      lead to full phosphotransferase capacity.

PMID- 11971898
TI  - Central region of the human splicing factor Hprp3p interacts with Hprp4p.
AB  - Human splicing factors Hprp3p and Hprp4p are associated with the U4/U6 small
      nuclear ribonucleoprotein particle, which is essential for the assembly of an
      active spliceosome. Currently, little is known about the specific roles of these
      factors in splicing. In this study, we characterized the molecular interaction
      between Hprp3p and Hprp4p. Constructs were created for expression of Hprp3p or
      its mutants in bacterial or mammalian cells. We showed that antibodies against
      either Hprp3p or Hprp4p were able to pull-down the Hprp3p-Hprp4p complex formed
      in Escherichia coli lysates. By co-immunoprecipitation and isothermal titration
      calorimetry, we demonstrated that purified Hprp3p and its mutants containing the
      central region, but lacking either the N-terminal 194 amino acids or the C
      terminal 240 amino acids, were able to interact with Hprp4p. Conversely, Hprp3p
      mutants containing only the N- or C-terminal region did not interact with Hprp4p.
      In addition, by co-immunoprecipitation, we showed that intact Hprp3p and its
      mutants containing the central region interacted with Hprp4p in HeLa cell nuclear
      extracts. Primer extension analysis illustrated that the central region of Hprp3p
      is required to maintain the association of Hprp3p-Hprp4p with U4/U6 small nuclear
      RNAs, suggesting that this Hprp3p/Hprp4p interaction allows the recruitment of
      Hprp4p, and perhaps other protein(s), to the U4/U6 small nuclear
      ribonucleoprotein particle.

PMID- 11971899
TI  - NADPH-cytochrome P-450 reductase in the plasma membrane modulates the activation
      of hypoxia-inducible factor 1.
AB  - Hypoxia induces a group of physiologically important genes that include
      erythropoietin (EPO) and vascular endothelial growth factor (VEGF). Hypoxia
      inducible factor 1 (HIF-1) was identified as a hypoxia-activated transcription
      factor; however, the molecular mechanisms that underlie hypoxia signal
      transduction in mammalian cells remain undefined. In this study, we found that a
      flavoprotein, NADPH-P450 reductase (NPR), could regulate the induction of EPO
      mRNA under hypoxic conditions. Hypoxic EPO mRNA induction in Hep3B cells was
      inhibited by diphenyleneiodonium chloride, which is an inhibitor of NADPH
      dependent enzymes. NPR antisense cDNA was transfected into Hep3B cells, and NPR
      deficient hepatocyte cells (NPR(-) cells) were established. NPR(-) cells lacked
      EPO induction under hypoxia, and HIF-1alpha in NPR(-) cells did not respond to
      either transcriptional activation or translocation to the nucleus based on
      electrophoretic mobility shift assays and reporter gene assay including hypoxia
      response element. In contrast, NPR overexpression in Hep3B cells enhanced the DNA
      binding activity of HIF-1alpha by luciferase reporter gene assay. A study with
      HeLa S3 cells produced the same results. Furthermore, anti-NPR IgG inhibited EPO
      induction. EPO induction inhibited by diphenyleneiodonium chloride was recovered
      by bovine serum albumin-NADPH (a covalent binding complex of bovine serum albumin
      and NADPH) as well as NADPH. These results suggested that NPR located at the
      plasma membrane regulates EPO expression in hypoxia, including HIF-1 activation
      and translocation. We further studied the expression of NPR and VEGF mRNAs in
      human tumor tissues and found that the NPR mRNA levels were correlated with the
      VEGF mRNA levels, suggesting that NPR might be an important factor in the hypoxic
      induction of genes such as VEGF in vivo.

PMID- 11971900
TI  - Nuclear import strategies of high risk HPV16 L1 major capsid protein.
AB  - During the late phase of human papillomavirus (HPV) infection, the L1 major
      capsid proteins enter the nuclei of host epithelial cells and, together with the
      L2 minor capsid proteins, assemble the replicated viral DNA into virions. We
      investigated the nuclear import of the L1 major capsid protein of high risk
      HPV16. When digitonin-permeabilized HeLa cells were incubated with HPV16 L1
      capsomeres, the L1 protein was imported into the nucleus in a receptor-mediated
      manner. HPV16 L1 capsomeres formed complexes with Kap alpha2beta1 heterodimers
      via interaction with Kap alpha2. Accordingly, nuclear import of HPV16 L1
      capsomeres was mediated by Kap alpha2beta1 heterodimers, required RanGDP and free
      GTP, and was independent of GTP hydrolysis. Remarkably, HPV16 L1 capsomeres also
      interacted with Kap beta2 and binding of RanGTP to Kap beta2 did not dissociate
      the HPV16 L1.Kap beta2 complex. Significantly, HPV16 L1 capsomeres inhibited the
      nuclear import of Kap beta2 and of a Kap beta2-specific M9-containing cargo.
      These data suggest that, during the productive stage of infection, while the
      HPV16 L1 major capsid protein enters the nucleus via the Kap alpha2beta1-mediated
      pathway to assemble the virions, it also inhibits the Kap beta2-mediated nuclear
      import of host hnRNP A1 protein and, in this way, favors virion formation.

PMID- 11971901
TI  - Regulation of Ikappa B kinase (IKK)gamma /NEMO function by IKKbeta -mediated
      phosphorylation.
AB  - The IkappaB kinase (IKK) complex includes the catalytic components IKKalpha and
      IKKbeta in addition to the scaffold protein IKKgamma/NEMO. Increases in the
      activity of the IKK complex result in the phosphorylation and subsequent
      degradation of IkappaB and the activation of the NF-kappaB pathway. Recent data
      indicate that the constitutive activation of the NF-kappaB pathway by the human T
      cell lymphotrophic virus, type I, Tax protein leads to enhanced phosphorylation
      of IKKgamma/NEMO by IKKbeta. To address further the significance of IKKbeta
      mediated phosphorylation of IKKgamma/NEMO, we determined the sites in
      IKKgamma/NEMO that were phosphorylated by IKKbeta, and we assayed whether
      IKKgamma/NEMO phosphorylation was involved in modulating IKKbeta activity.
      IKKgamma/NEMO is rapidly phosphorylated following treatment of cells with stimuli
      such as tumor necrosis factor-alpha and interleukin-1 that activate the NF-kappaB
      pathway. By using both in vitro and in vivo assays, IKKbeta was found to
      phosphorylate IKKgamma/NEMO predominantly in its carboxyl terminus on serine
      residue 369 in addition to sites in the central region of this protein.
      Surprisingly, mutation of these carboxyl-terminal serine residues increased the
      ability of IKKgamma/NEMO to stimulate IKKbeta kinase activity. These results
      indicate that the differential phosphorylation of IKKgamma/NEMO by IKKbeta and
      perhaps other kinases may be important in regulating IKK activity.

PMID- 11971902
TI  - Coordinate Notch3-hairy-related transcription factor pathway regulation in
      response to arterial injury. Mediator role of platelet-derived growth factor and
      ERK.
AB  - The Notch family of receptors and downstream effectors plays a critical role in
      cell fate determination during vascular ontogeny. Moreover, the human cerebral
      autosomal dominant artriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL) syndrome of premature stroke and dementia is a heritable arteriopathy
      with alterations in vascular smooth muscle cells (VSMCs) resulting from mutations
      within Notch3. However, the expression and regulation of the Notch and hairy
      related transcription factor (HRT) pathway in adult VSMCs in vitro and in vivo
      remain poorly characterized. The present study documents that the well-described
      modulation of VSMC fate in response to vascular injury and growth factor
      activation involves a coordinate regulation of the Notch and HRT pathways.
      Furthermore, platelet-derived growth factor promotes a similar coordinate down
      regulation of the Notch receptors and HRT genes in cultured VSMCs via an ERK
      dependent signaling pathway. Moreover, we established that HRT1 and HRT2 are
      direct downstream target genes of Notch3 signaling in VSMCs and determined that
      the activity of the nuclear protein RBP-Jk is essential for their regulation.
      These findings provide initial insight into the context- and cell type-dependent
      coordinate regulation of Notch3 and downstream HRT transcriptional pathway
      effector genes in VSMCs in vitro and in vivo that may have important implications
      for understanding the role of Notch signaling in human health and vascular
      disease.

PMID- 11971903
TI  - Nitric-oxide reductase. Structure and properties of the catalytic site from
      resonance Raman scattering.
AB  - We have applied resonance Raman spectroscopy to investigate the properties of the
      dinuclear center of oxidized, reduced, and NO-bound nitric-oxide reductase from
      Paracoccus denitrificans. The spectra of the oxidized enzyme show two distinct
      nu(as)(Fe-O-Fe) modes at 815 and 833 cm(-1) of the heme/non-heme diiron center.
      The splitting of the Fe-O-Fe mode suggests that two different conformations (open
      and closed) are present in the catalytic site of the enzyme. We find evidence
      from deuterium exchange experiments that in the dominant conformation (833 cm(-1)
      mode, closed), the Fe-O-Fe unit is hydrogen-bonded to distal residue(s). The
      ferric nitrosyl complex of nitric-oxide reductase exhibits the nu(Fe(3+)-NO) and
      nu(N-O) at 594 and 1904 cm(-1), respectively. The nitrosyl species we detect is
      photolabile and can be photolyzed to generate a new form of oxidized enzyme in
      which the proximal histidine is ligated to heme b(3), in contrast to the resting
      form. Photodissociation of the NO ligand yields a five-coordinate high-spin heme
      b(3). Based on the findings reported here, the structure and properties of the
      dinuclear center of nitric- oxide reductase in the oxidized, reduced, and NO
      bound form as well as its photoproduct can be described with certainty.

PMID- 11971904
TI  - A de novo designed template for generating conformation-specific antibodies that
      recognize alpha-helices in proteins.
AB  - The generation of antibodies directed toward the surface-exposed regions of a
      protein using synthetic peptides as immunogens representing surface loops and
      turns has been widely successful. However, peptides representing alpha-helical
      regions are typically unstructured in solution and unable to produce antibodies
      that recognize alpha-helices in native proteins. We describe a de novo designed
      parallel two-stranded alpha-helical coiled-coil template for immunization to
      prepare antibodies that recognize alpha-helical protein sequences in the native
      protein. This template was designed for maximum stability through an Ile/Leu
      hydrophobic core and an interchain disulfide bridge. Surface-exposed helical
      residues are inserted into the template and used for immunization to generate
      polyclonal antibodies. To demonstrate the feasibility of this approach, 15
      residues of the yeast transcription factor GCN4 were inserted into this template,
      and the resultant antibodies were screened for conformational specificity.
      Peptide antigens that contain the same surface-exposed residues but differ in
      structure were used as competitors in a competition assay. Direct competition
      between the capture peptide immobilized on a biosensor chip, the peptide
      antigens, and the antibodies generated by the template demonstrated that the
      antibodies were specific for helical structure in the native coiled-coil
      (synthetic GCN4 residues 250-280). These antibodies were unable to recognize the
      same inserted sequence in an unstructured analog. The helix-specific antibodies
      were also able to identify native GCN4 (31.3 kDa) from yeast whole cell extracts.

PMID- 11971905
TI  - Analysis of nucleotide binding to Dictyostelium myosin II motor domains
      containing a single tryptophan near the active site.
AB  - Dictyostelium myosin II motor domain constructs containing a single tryptophan
      residue near the active sites were prepared in order to characterize the process
      of nucleotide binding. Tryptophan was introduced at positions 113 and 131, which
      correspond to those naturally present in vertebrate skeletal muscle myosin, as
      well as position 129 that is also close to the adenine binding site. Nucleotide
      (ATP and ADP) binding was accompanied by a large quench in protein fluorescence
      in the case of the tryptophans at 129 and 131 but a small enhancement for that at
      113. None of these residues was sensitive to the subsequent open-closed
      transition that is coupled to hydrolysis (i.e. ADP and ATP induced similar
      fluorescence changes). The kinetics of the fluorescence change with the F129W
      mutant revealed at least a three-step nucleotide binding mechanism, together with
      formation of a weakly competitive off-line intermediate that may represent a
      nonproductive mode of nucleotide binding. Overall, we conclude that the local and
      global conformational changes in myosin IIs induced by nucleotide binding are
      similar in myosins from different species, but the sign and magnitude of the
      tryptophan fluorescence changes reflect nonconserved residues in the immediate
      vicinity of each tryptophan. The nucleotide binding process is at least three
      step, involving conformational changes that are quite distinct from the open
      closed transition sensed by the tryptophan Trp(501) in the relay loop.

PMID- 11971906
TI  - Ternary complex formation between MADS-box transcription factors and the histone
      fold protein NF-YB.
AB  - MADS-box proteins are transcription factors present in different eukaryotic
      kingdoms. In contrast to plants, for mammalian and yeast MADS-box proteins
      ternary complex formation with unrelated transcription factors was reported. We
      show here the first identification of such ternary interaction in plants. A rice
      seed-specific NF-YB was identified as partner of OsMADS18 by two-hybrid
      screening. NF-YB contains a histone fold motif, HFM,(1) and is part of the
      trimeric CCAAT-binding NF-Y complex. OsMADS18, alone or in combination with a
      natural partner, interacts with OsNF-YB1 through the MADS and I regions. The
      mouse NF-YB also associates with OsMADS18 in vivo and in vitro as a NF-YB-NF-YC
      dimer. Other rice MADS-box proteins do not interact in these assays, indicating
      specificity for the interaction. OsNF-YB1 is capable of heterodimerizing with NF
      YC, but not trimerizing with NF-YA, thus precluding CCAAT binding. Mutation of
      the variant Asp at position 99 of the HFM alpha2-helix into a conserved serine
      recovers the capacity to interact with NF-YA, but not with DNA. This is the first
      indication that members of the NF-YB family work through mechanisms independent
      of the CCAAT box.

PMID- 11971907
TI  - Myotrophin/V-1, a protein up-regulated in the failing human heart and in
      postnatal cerebellum, converts NFkappa B p50-p65 heterodimers to p50-p50 and p65
      p65 homodimers.
AB  - Myotrophin/V-1 is a cytosolic protein found at elevated levels in failing human
      hearts and in postnatal cerebellum. We have previously shown that it disrupts
      nuclear factor of kappaB (NFkappaB)-DNA complexes in vitro. In this study, we
      demonstrated that in HeLa cells native myotrophin/V-1 is predominantly present in
      the cytoplasm and translocates to the nucleus during sustained NFkappaB
      activation. Three-dimensional alignment studies indicate that myotrophin/V-1
      resembles a truncated IkappaBalpha without the signal response domain (SRD) and
      PEST domains. Co-immunoprecipitation studies reveal that myotrophin/V-1 interacts
      with NFkappaB proteins in vitro; however, it remains physically associated only
      with p65 and c-Rel proteins in vivo during NFkappaB activation. In vitro studies
      indicate that myotrophin/V-1 can promote the formation of p50-p50 homodimers from
      monomeric p50 proteins and can convert the preformed p50-p65 heterodimers into
      p50-p50 and p65-p65 homodimers. Furthermore, adenovirus-mediated overexpression
      of myotrophin/V-1 resulted in elevated levels of both p50-p50 and p65-p65
      homodimers exceeding the levels of p50-p65 heterodimers compared with Adbetagal
      infected cells, where the levels of p50-p65 heterodimers exceeded the levels of
      p50-p50 and p65-p65 homodimers. Thus, overexpression of myotrophin/V-1 during
      NFkappaB activation resulted in a qualitative shift by quantitatively reducing
      the level of transactivating heterodimers while elevating the levels of
      repressive p50-p50 homodimers. Correspondingly, overexpression of myotrophin/V-1
      resulted in significantly reduced kappaB-luciferase reporter activity. Because
      myotrophin/V-1 is found at elevated levels during NFkappaB activation in
      postnatal cerebellum and in failing human hearts, this study cumulatively
      suggests that myotrophin/V-1 is a regulatory protein for modulating the levels of
      activated NFkappaB dimers during this period.

PMID- 11971909
TI  - Elimination of P1 arginine 393 interaction with underlying glutamic acid 255
      partially activates antithrombin III for thrombin inhibition but not factor Xa
      inhibition.
AB  - The mechanism for heparin activation of antithrombin III has been postulated to
      involve disruption of interactions between its reactive loop P1 residue and
      Glu(255) on the underlying protein surface. To test this hypothesis, the
      potential P1-constraining Arg(393)-Glu(255) hydrogen bond and ionic interactions
      were eliminated by converting Glu(255) to alanine. E255A and wild-type ATIIIs
      have identical reactive loop sequences (including the P1 and P14 residues), but
      differ in that Glu(255)-mediated, P1-constraining interactions with the
      underlying surface cannot form in the mutant. Relative to its wild-type parent,
      E255A had a 5-fold higher affinity for heparin and pentasaccharide. In the
      absence of cofactor, E255A exhibited a 5-fold activation of thrombin inhibition
      but no activation of factor Xa inhibition. Pentasaccharide addition elicited no
      further activation of thrombin inhibition but increased the factor Xa inhibition
      rate 100-fold. E255A heparin-dependent thrombin and factor Xa inhibition rates
      were 1000- and 2-fold faster, respectively, than pentasaccharide-catalyzed rates.
      Although "approximation" is the predominant factor in heparin activation of ATIII
      thrombin inhibition, and removal of the P1 constraint plays a distinct but minor
      role, the primary determinant for activation of factor Xa inhibition is the
      pentasaccharide-induced conformational change, with approximation making a
      further minor contribution, and removal of the P1 constraint playing no role at
      all.

PMID- 11971908
TI  - Epidermal growth factor-mediated activation of the ETS domain transcription
      factor Elk-1 requires nuclear calcium.
AB  - Cytosolic and nuclear Ca(2+) have been shown to differentially regulate
      transcription. However, the impact of spatially distinct Ca(2+) signals on
      mitogen-activated protein kinase-mediated gene expression remains unknown. Here
      we investigated the role of nuclear and cytosolic Ca(2+) signals in epidermal
      growth factor (EGF)-induced transactivation of the ternary complex factor Elk-1
      using a GAL4-Elk-1 construct. EGF increased Ca(2+) in both the nucleus and
      cytosol of HepG2 or 293 cells. Pretreatment with the intracellular Ca(2+)
      chelator bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid
      significantly reduced EGF-induced transactivation of Elk-1, indicating that EGF
      stimulated Elk-1 transcriptional activity is dependent on intracellular Ca(2+).
      To determine the relative contribution of nuclear and cytosolic Ca(2+) signals
      during EGF-mediated Elk-1 transactivation, Ca(2+) signals in either compartment
      were selectively impaired by targeted expression of the Ca(2+)-binding protein
      parvalbumin to either the nucleus or cytosol. Suppression of nuclear but not
      cytosolic Ca(2+) signals inhibited EGF-induced transactivation of Elk-1. However,
      suppression of nuclear Ca(2+) signals did not affect the ability of ERK either to
      become phosphorylated or to undergo translocation to the nucleus in response to
      EGF. Elk-1 phosphorylation and nuclear localization following EGF stimulation
      were also unaffected by suppressing nuclear Ca(2+) signals. These results suggest
      that nuclear Ca(2+) is required for EGF-mediated transcriptional activation of
      Elk-1 and that phosphorylation of Elk-1 alone is not sufficient to induce its
      transcriptional activation in response to EGF. Thus, subcellular targeting of
      parvalbumin reveals a distinct role for nuclear Ca(2+) signals in mitogen
      activated protein kinase-mediated gene transcription.

PMID- 11971910
TI  - Modular organization of phylogenetically conserved domains controlling
      developmental regulation of the human skeletal myosin heavy chain gene family.
AB  - The mammalian skeletal myosin heavy chain locus is composed of a six-membered
      family of tandemly linked genes whose complex regulation plays a central role in
      striated muscle development and diversification. We have used publicly available
      genomic DNA sequences to provide a theoretical foundation for an experimental
      analysis of transcriptional regulation among the six promoters at this locus.
      After reconstruction of annotated drafts of the human and murine loci from
      fragmented DNA sequences, phylogenetic footprint analysis of each of the six
      promoters using standard and Bayesian alignment algorithms revealed unexpected
      patterns of DNA sequence conservation among orthologous and paralogous gene
      pairs. The conserved domains within 2.0 kilobases of each transcriptional start
      site are rich in putative muscle-specific transcription factor binding sites.
      Experiments based on plasmid transfection in vitro and electroporation in vivo
      validated several predictions of the bioinformatic analysis, yielding a picture
      of synergistic interaction between proximal and distal promoter elements in
      controlling developmental stage-specific gene activation. Of particular interest
      for future studies of heterologous gene expression is a 650-base pair construct
      containing modules from the proximal and distal human embryonic myosin heavy
      chain promoter that drives extraordinarily powerful transcription during muscle
      differentiation in vitro.

PMID- 11971911
TI  - Linking drought-resistance mechanisms to drought avoidance in upland rice using a
      QTL approach: progress and new opportunities to integrate stomatal and mesophyll
      responses.
AB  - The advent of saturated molecular maps promised rapid progress towards the
      improvement of crops for genetically complex traits like drought resistance via
      analysis of quantitative trait loci (QTL). Progress with the identification of
      QTLs for drought resistance-related traits in rice is summarized here with the
      emphasis on a mapping population of a cross between drought-resistant varieties
      Azucena and Bala. Data which have used root morphological traits and indicators
      of drought avoidance in field-grown plants are reviewed, highlighting problems
      and uncertainties with the QTL approach. The contribution of root-growth QTLs to
      drought avoidance appears small in the experiments so far conducted, and the
      limitations of screening methodologies and the involvement of shoot-related
      mechanisms of drought resistance are studied. When compared to Azucena, Bala has
      been observed to have highly sensitive stomata, does not roll its leaves readily,
      has a greater ability to adjust osmotically, slows growth more rapidly when
      droughted and has a lower water-use efficiency. It is also a semi-dwarf variety
      and hence has a different canopy structure. There is a need to clarify the
      contribution of the shoot to drought resistance from the level of the
      biochemistry of photosynthesis through stomatal behaviour and leaf anatomy to
      canopy architecture. Recent advances in studying the physical and biochemical
      processes related to water use and drought stress offer the opportunity to
      advance a more holistic understanding of drought resistance. These include the
      potential use of infrared thermal imaging to study energy balance, integrated and
      online stable isotope analysis to dissect processes involved in carbon dioxide
      fixation and water evaporation, and leaf fluorescence to monitor photosynthesis
      and photochemical quenching. Justification and a strategy for this integrated
      approach is described, which has relevance to the study of drought resistance in
      most crops.

PMID- 11971912
TI  - Characterization of Arabidopsis photolyase enzymes and analysis of their role in
      protection from ultraviolet-B radiation.
AB  - DNA photolyases are enzymes which mediate the light-dependent repair
      (photoreactivation) of UV-induced damage products in DNA by direct reversal of
      base damage rather than via excision repair pathways. Arabidopsis thaliana
      contains two photolyases specific for photoreactivation of either cyclobutane
      pyrimidine dimers (CPDs) or pyrimidine (6-4)pyrimidones (6-4PPs), the two major
      UV-B-induced photoproducts in DNA. Reduced FADH and a reduced pterin were
      identified as cofactors of the native Arabidopsis CPD photolyase protein. This is
      the first report of the chromophore composition of any native class II CPD
      photolyase protein to our knowledge. CPD photolyase protein levels vary between
      tissues and with leaf age and are highest in flowers and leaves of 3-5-week-old
      Arabidopsis plants. White light or UV-B irradiation induces CPD photolyase
      expression in Arabidopsis tissues. This contrasts with the 6-4PP photolyase
      protein which is constitutively expressed and not regulated by either white or UV
      B light. Arabidopsis CPD and 6-4PP photolyase enzymes can remove UV-B-induced
      photoproducts from DNA in planta even when plants are grown under enhanced levels
      of UV-B irradiation and at elevated temperatures although the rate of removal of
      CPDs is slower at high growth temperatures. These studies indicate that
      Arabidopsis possesses the photorepair capacity to respond effectively to
      increased UV-B-induced DNA damage under conditions predicted to be representative
      of increases in UV-B irradiation levels at the Earth's surface and global warming
      in the twenty-first century.

PMID- 11971913
TI  - Nuclear DNA endoreduplication during petal development in cabbage: relationship
      between ploidy levels and cell size.
AB  - The development of cabbage petals comprises two distinct phases: a cell division
      phase and a consecutive phase of cell expansion until the onset of opening. In
      this study, cytological changes characterizing the two phases of petal
      development were analysed. First, the mitotic activity and the surface area of
      epidermal cells during petal development were investigated. The DNA content of
      isolated nuclei from the different stages of petal tissues was determined by flow
      cytometric analysis. The results show that cell differentiation, leading to
      expanded cells, is characterized by endoreduplication. In the proximal part of
      the petal, after cell division arrest, differentiation frequently involves
      endoreduplication and cell enlargement. By contrast, normal diploid nuclei
      remained in the distal part of the lamina in the mature petal. It is suggested
      that the developmental programmes of the cabbage petal may be a trigger for the
      initiation of endoreduplication. Correlation between ploidy levels and cell size
      is also discussed.

PMID- 11971914
TI  - Cloning and characterization of four apple MADS box genes isolated from
      vegetative tissue.
AB  - With the aim of finding genes involved in the floral transition of woody species
      four MADS box genes containing cDNAs from apple (Malus domestica) have been
      isolated. Three genes were isolated from vegetative tissue of apple, but were
      homologues of known genes that specify floral organ identity. MdMADS13 is an AP3
      like B class MADS box gene, and was mainly expressed in petals and stamens as
      demonstrated by Northern blot analysis. MdMADS14 and -15 are AGAMOUS-like genes.
      They differed slightly in expression patterns on Northern blots, with MdMADS15
      mRNA levels equally high in stamens and carpels, but MdMADS14 preferably
      expressed in carpels. MdMADS14 is likely to be the apple orthologue of one of the
      Arabidopsis thaliana SHATTERPROOF genes, and MdMADS15 closely resembled the
      Arabidopsis AGAMOUS gene. It has been shown with RT-PCR that the three floral
      apple MADS box genes are expressed in vegetative tissues of adult as well as
      juvenile trees, albeit at low levels. MdMADS12 is an AP1-like gene that is
      expressed at similar levels in leaves, vegetative shoots, and floral tissues, and
      that may be involved in the transition from the juvenile to the adult stage.

PMID- 11971915
TI  - Glasshouse behaviour of eight transgenic potato clones with a modified nitrate
      reductase expression under two fertilization regimes.
AB  - In this study, eight transformed Solanum tuberosum L. plants, affected in their
      nitrate assimilatory pathway by the introduction of a tobacco nitrate reductase
      gene (Nia2), were cultivated in glasshouse conditions at INRA Ploudaniel (West
      Brittany, France). Two irrigation regimes were compared and plants were sampled
      at four stages of vegetation. Yield, tuber dry matter content, total nitrogen
      content, nitrate content in the whole plant, and nitrate reductase activities
      were studied. High frequency irrigation with nutritive solutions negatively
      affects both yield and dry matter content in tubers. Moreover, the introduction
      of the tobacco Nia2 gene in the potato genome does not seem to affect the
      agronomical parameters of the initial genotype apart from the nitrate content of
      tubers. Five transgenic genotypes out of eight, in fact, showed a drastic
      decrease (of around 98%) in their tuber nitrate content. This nitrate decrease in
      the tubers was also correlated with the presence of the mRNA transgene, whereas
      the potato nitrate reductase transcript does not seem to be expressed in wild
      type tubers. Regarding these genotypes, developmental stage and nutritive
      solution supply were found to have no effect on tuber nitrate content. In fact,
      tubers derived from these clones exhibited low nitrate content throughout the
      vegetation period, while nitrate accumulation in wild-type tubers is progressive
      and increases sharply with high nutritive solution supply.

PMID- 11971916
TI  - Distinct nuclear organization, DNA methylation pattern and cytokinin distribution
      mark juvenile, juvenile-like and adult vegetative apical meristems in peach
      (Prunus persica (L.) Batsch).
AB  - Chromatin organization, nuclear DNA methylation and endogenous zeatin
      localization were investigated in shoot apical meristems (SAM) during juvenile
      and adult phases of peach (Prunus persica (L.) Batsch). The aim was to examine
      the extent to which these parameters could discriminate the juvenile and adult
      SAMs. Seedlings (juvenile, cannot flower), basal shoots (called juvenile-like,
      because they exhibit juvenile macroscopic traits) and apical shoots (competent to
      form flowers) of adult plants were chosen. Nuclear chromatin exhibited
      chromocentres that were peripherally distributed in SAMs of juvenile and juvenile
      like shoots, but were diffusely spread in those of adult shoots. These patterns
      coincided with a peripheral labelling of DNA methylation in juvenile and juvenile
      like meristem nuclei versus a diffuse labelling pattern in adult meristem nuclei.
      During vegetative growth (from March to June), the level of nuclear DNA
      methylation was higher in adult meristems than in juvenile and juvenile-like
      ones. The immunolocalization of zeatin in juvenile SAM was in the subapical
      region, but adult meristems exhibited a widespread localization or a signal
      confined within the boundaries of the central zone. The extent to which the
      acquisition of a strongly zonated pattern of these parameters as markers of
      floral competence in adult SAMs is discussed.

PMID- 11971917
TI  - Increased vacuolar Na(+)/H(+) exchange activity in Salicornia bigelovii Torr. in
      response to NaCl.
AB  - Shoots of the halophyte Salicornia bigelovii are larger and more succulent when
      grown in highly saline environments. This increased growth and water uptake has
      been correlated with a large and specific cellular accumulation of sodium. In
      glycophytes, sensitivity to salt has been associated with an inability to remove
      sodium ions effectively from the cytoplasm in order to protect salt-sensitive
      metabolic processes. Therefore, in Salicornia bigelovii efficient vacuolar
      sequestration of sodium may be part of the mechanism underlying salt tolerance.
      The ability to compartmentalize sodium may result from a stimulation of the
      proton pumps that provide the driving force for increased sodium transport into
      the vacuole via a Na(+)/H(+) exchanger. In current studies, increased vacuolar
      pyrophosphatase activity (hydrolysis of inorganic pyrophosphate and proton
      translocation) and protein accumulation were observed in Salicornia bigelovii
      grown in high concentrations of NaCl. Based on sodium-induced dissipation of a
      pyrophosphate-dependent pH gradient in vacuolar membrane vesicles, a Na(+)/H(+)
      exchange activity was identified and characterized. This activity is sodium
      concentration-dependent, specific for sodium and lithium, sensitive to methyl
      isobutyl amiloride, and independent of an electrical potential. Vacuolar
      Na(+)/H(+) exchange activity varied as a function of plant growth in salt. The
      affinity of the transporter for Na(+) is almost three times higher in plants
      grown in high levels of salt (K(m)=3.8 and 11.5 mM for plants grown in high and
      low salt, respectively) suggesting a role for exchange activity in the salt
      adaptation of Salicornia bigelovii.

PMID- 11971918
TI  - Guard cell wall: immunocytochemical detection of polysaccharide components.
AB  - The composition of guard cell walls in sugar beet leaves (Beta vulgaris L.) was
      studied by using histochemical staining and immunocytochemical detection of cell
      wall antigens. The findings were compared with those in the walls of epidermal
      and mesophyll cells. Probing of leaf sections with monoclonal antibodies against
      pectins, terminal fucosyl residues linked alpha-(1-->2) to galactose, beta-(1-
      >3)-glucans and arabinogalactan-proteins revealed several specific features of
      guard cells. Pectic epitopes recognized by JIM7 were homogeneously distributed in
      the wall, whereas pectins recognized by JIM5 were not found in the walls
      themselves, but were abundant in the cuticular layer. Large amounts of molecules
      bearing terminal fucose were located predominantly in ventral and lateral guard
      cell walls. Much smaller amounts were detected in dorsal walls of these cells, as
      well as in the walls of pavement and mesophyll cells. Conspicuous accumulation of
      these compounds was observed in the vicinity of the guard cell plasmalemma,
      whereas labelling was scarce in the areas of the wall adjacent to the cell
      surface. The presence of callose clearly marked the ventral wall between the
      recently formed, very young guard cells. Callose also appeared in some mature
      walls, where it was seen as punctate deposits that probably reflected a specific
      physiological state of the guard cells. Large amounts of arabinogalactan-proteins
      were deposited within the cuticle, and smaller amounts of these proteoglycans
      were also detected in other tissues of the leaf. The histochemical and
      immunocytochemical structure of the guard cell wall is discussed in the light of
      its multiple functions, most of which involve changes in cell size and shape.

PMID- 11971919
TI  - Role of sugars and organic acids in regulating the concentration and activity of
      the alternative oxidase in Poa annua roots.
AB  - Detached roots of Poa annua were used to study alternative oxidase protein
      expression upon the addition of sucrose, glucose, fructose, inositol, mannitol,
      citrate or malate, at a concentration of 1 or 10 mM for 24 h. After 24 h the
      capacity of cytochrome c oxidase was decreased equally in all treatments. Only
      citrate induced the expression of the alternative oxidase, especially at a
      concentration of 1 mM (15-fold). The activity of the alternative pathway
      (measured with the (18)O-fractionation technique) was not affected by the
      addition of sucrose for 24 h as compared with time zero. However, after the
      addition of citrate or mannitol the activity of the alternative pathway decreased
      to almost zero. The discrepancy between the large increase in alternative oxidase
      protein concentration when citrate was applied and the concomitant decrease in
      alternative pathway activity is discussed.

PMID- 11971920
TI  - A comparison of the effects of IAA and 4-Cl-IAA on growth, proton secretion and
      membrane potential in maize coleoptile segments.
AB  - The physiological activity of exogenous 4-Cl-IAA, as compared to IAA, was
      examined in maize coleoptile segments. It was found that in this model system 4
      Cl-IAA is much more active in the stimulation of elongation than IAA.
      Simultaneous measurements of growth and external pH indicated that administration
      of either IAA or 4-Cl-IAA resulted in medium acidification. The kinetics of the
      pH changes, however, were faster after the addition of 4-Cl-IAA. In contrast to
      IAA, the coleoptile segments treated with chlorinated auxin were not able to
      increase medium pH after its initial drop. The re-addition of IAA after 5 h
      further enhanced growth over the next 2 h by 31%. By contrast, the re-addition of
      4-Cl-IAA at the same time protocol as IAA did not cause an additional effect. The
      administration of 10 microM IAA induced in maize coleoptile cells a transient
      depolarization followed by a slow hyperpolarization of their membrane potential.
      In contrast to IAA, 4-Cl-IAA at 1 microM caused an immediate hyperpolarization of
      the membrane potential which, on average, was 2-fold greater than for IAA. The
      results reported here provide further evidence that 4-Cl-IAA is much more active,
      as compared to IAA, in stimulating the growth of maize coleoptile segments.
      Although it has not been directly demonstrated here, a plausible interpretation
      for the high 4-Cl-IAA activity is that, at least in part, it might be caused via
      a reduced metabolism of 4-Cl-IAA. Furthermore, for the first time, the data show
      that membrane potential responds to 4-Cl-IAA in a qualitatively different fashion
      than to IAA. These findings may, in turn, suggest a specific signal transduction
      pathway to 4-Cl-IAA in maize coleoptile cells.

PMID- 11971921
TI  - Legume embryos develop in a hypoxic environment.
AB  - Specific morphological and biochemical characteristics of seeds can cause oxygen
      deficiency within maternal and embryonic tissues. In this study, optical sensors
      were used to measure O(2) profiles across developing seeds of Vicia faba and
      Pisum sativum and developmental and environmental modulations of internal O(2)
      levels were studied. In addition, the metabolic state of developing embryos was
      analysed by monitoring adenylate energy charge, adenylate nucleotides and the
      levels of nucleotide sugars. Within the seed coat O(2) concentration decreased
      sharply to approximately 3% towards the inner border. Lowest O(2) levels were
      detected within the endospermal cavity between the seed coat and embryo. It is
      probable that low seed coat permeability provides an hypoxic environment for
      legume embryo development. The O(2) concentration in embryonic tissue changed
      during development with the lowest levels in the early stages. Measured in
      darkness, the levels were below 3%, but increased upon illumination indicating
      that photosynthesis significantly contributes to internal O(2) levels. Only in
      very young embryos were ATP levels and energy charge low. Otherwise they were
      maintained at a constant higher value. ADP-glucose and UDP-glucose did not show
      large fluctuations. Throughout embryo development fermentative activity did not
      play a major role. Obviously, specific mechanisms prevent seed tissues from
      becoming anoxic during development. The possible role of low oxygen on seed
      metabolism and on the control of seed development in legumes is discussed.

PMID- 11971922
TI  - Difference in delta(15)N signatures between nodulated roots and shoots of soybean
      is indicative of the contribution of symbiotic N(2) fixation to plant N.
AB  - Symbiotic N(2) fixation has a variable effect on the (15)N abundance of different
      parts of legumes. Increases in fixation result in (15)N enrichment of nodules,
      while decreases, in combination with an increased uptake of mineral N, result in
      (15)N depletion of the root system. The difference between soybean shoot and
      below-ground delta(15)N (Deltadelta(15)N=delta(15)N(shoot)
      delta(15)N(belowground)) was assessed in hydroponic culture over a range of rates
      of supply of mineral N. The fractional contribution of N(2) fixation to N uptake
      (%Ndfa) was determined using the natural abundance (NA) technique with ryegrass
      as a reference plant. Deltadelta(15)N and %Ndfa were highly correlated, and the
      relationship was tested using the same soybean cultivar grown in pots in N-rich
      soil. Estimates of %Ndfa derived from the NA method and from the Deltadelta(15)N
      approach yielded near-identical values. A literature survey showed similar
      relationships between %Ndfa and Deltadelta(15)N with different growth stages of
      soybeans grown under glasshouse and field conditions, different cowpea (Vigna
      unguiculata) cultivars in the field, and tagasaste (Chamaecytisus proliferus) in
      hydroponic culture. Possible confounding and species-specific (either plant or
      Rhizobium spp.) influences are discussed. The difference in delta(15)N signatures
      between nodulated roots and shoots is confirmed as a robust means of quantifying
      %Ndfa: it is independent of reference plants and offers the possibility of
      estimating %Ndfa in soils where the isotope composition of mineral N closely
      matches that of atmospheric N(2).

PMID- 11971923
TI  - Antirrhinum majus microspore maturation and transient transformation in vitro.
AB  - The male gametophyte of higher plants represents an excellent system to study
      gene regulation, cell fate determination and cellular differentiation in plants
      because of its relative simplicity compared to the sporophyte and its
      accessibility for cytological and molecular analysis. Unicellular plant
      microspores are single haploid cells, which can be isolated in large amounts at a
      defined developmental stage. Microspores cultured in vitro in a rich medium
      develop into mature pollen grains, which are fertile upon pollination in vivo. It
      is reported here that isolated Antirrhinum majus microspores when cultured in an
      optimal medium develop to form mature, fertile pollen. Their development closely
      resembled that of pollen formed in vivo. Isolated microspores were bombarded with
      Aquorea victoria Green Fluorescent Protein (GFP), Discosoma Red Fluorescent
      Protein (dsRFP) and beta-glucuronidase (GUS) reporter genes under the control of
      various promoters and transient expression was observed throughout pollen
      development in vitro. Bombarded and not bombarded in vitro-matured pollen grains
      were able to germinate both in vitro and on receptive stigmas and to set seed.
      The protocol of maturation, transient transformation and germination of
      Antirrhinum majus pollen in vitro described here provides a valuable tool for
      basic and applied research.

PMID- 11971924
TI  - Nitrogen storage and remobilization in Brassica napus L. during the growth cycle:
      effects of methyl jasmonate on nitrate uptake, senescence, growth, and VSP
      accumulation.
AB  - The role of methyl jasmonate (MeJa) in promoting senescence has been described
      previously in many species, but it has been questioned in monocarpic species
      whether induced senescence is a result of a potential death hormone like MeJa, or
      a consequence of an increased metabolic drain resulting from the growth of
      reproductive tissue. In oilseed rape (Brassica napus L.), a polypeptide of 23 kDa
      has been recently identified as a putative vegetative storage protein (VSP). This
      polypeptide could be used as a storage buffer between N losses from senescing
      leaves putatively promoted by methyl jasmonate that might be produced by flowers,
      and grain filling which occurs later on, while N uptake is strongly reduced. In
      order to describe causal relationships during Brassica napus L. plant responses
      to MeJa treatment, a kinetic experiment was performed to determine the order and
      the amplitude with which general processes such as growth, photosynthesis,
      chlorophyll content, N uptake, and N storage under the form of the 23 kDa VSP are
      affected. One of the most immediate consequences of MeJa treatment was the strong
      reduction of nitrate uptake within 6 h, relative to control plants. However, this
      was not a specific effect as K(+) uptake was similarly affected. Photosynthesis
      was reduced later (after 24 h), while chlorophyll content as well as leaf growth
      also decreased in a similar way. Moreover, this was concomitant with a
      remobilization of endogenous unlabelled N from senescing leaves to roots.
      Accumulation of the 23 kDa VSP was induced in the taproot after 24 h of MeJa
      treatment and was increased 10-fold within 8 d. On the other hand, the reversible
      effect of a MeJa pretreatment was tested in the long term (i.e. along the growth
      cycle) using plants previously grown in field conditions induced for flowering.
      Results show that a MeJa pulse induced a reversible effect on N uptake
      inhibition. In parallel, protein immunologically related to the 23 kDa VSP was
      detected in stems with a similar molecular weight (23 kDa), and in flowers and
      leaves with a molecular weight of 24 kDa. This accumulation was concomitant with
      the remobilization of both subunits of Rubisco. During stem and pod development,
      this protein induced by MeJa is fully hydrolysed. The external and intermittent
      supply of MeJa mimic some of the plant physiological processes previously
      reported under natural conditions. This suggests that in oilseed rape, methyl
      jasmonate could be considered as a possible monocarpic senescence factor while
      accumulation/mobilization of the 23 kDa VSP in taproot could be a marker for the
      cessation of N uptake and the initiation of a massive leaf senescence.

PMID- 11971925
TI  - Evidence for high activity of xylem parenchyma and ray cells in the interface of
      host stem and Agrobacterium tumefaciens-induced tumours of Ricinus communis.
AB  - Rapidly developing tumours at hypocotyls of Ricinus communis, induced by
      Agrobacterium tumefaciens strain C58, were characterized by strong
      differentiation of vascular bundles and their functional connection to the host
      bundles. The stem/tumour interface showed increased xylem, with numerous vessels
      accompanied by multiseriate unlignified rays. To know how nutrients efficiently
      accumulate in the tumour sink tissue, cell electropotentials (E(m)) in cross
      sections were mapped. The measured cells were identified by injected Lucifer
      Yellow. Xylem and phloem parenchyma cells and stem/tumour-located rays
      hyperpolarized to E(m) values of about -170 mV, which suggest high plasma
      membrane proton pump activities. Rapidly dividing cells of cambia or small tumour
      parenchyma cells had low E(m). The tumour aerenchyma and the stem cortex cells
      displayed values close to the energy-independent diffusion potential. The lowest
      values were recorded in stem pith cells. Cell K(+) concentrations largely matched
      the respective E(m). The pattern of individual cell electropotentials was
      supplemented by whole organ voltage measurements. The voltage differences between
      the tumour surface and the xylem perfusion solution in stems attached to the
      tumours, the trans-tumour electropotentials (TTP), confirm the findings of
      respiration-dependent and phytohormone-stimulated high plasma membrane proton
      pump activity in intact tumours, mainly in the xylem and phloem parenchyma and
      ray cells. TTPs were inhibited by addition of NaN(3), CN(-) plus SHAM or N(2) gas
      in the xylem perfusion solution and by external N(2) flushing. The data provide
      functional evidence for the structural basis of priority over the host shoot in
      nutrient flow from the stem to the tumour.

PMID- 11971926
TI  - Cavitation fatigue and its reversal in sunflower (Helianthus annuus L.).
AB  - "Cavitation fatigue" is the increased susceptibility of a xylem conduit to
      cavitation as a result of its prior cavitation. It was investigated whether
      cavitation fatigue induced in vivo could be repaired in intact plants. Sunflowers
      (Helianthus annuus L.) were subjected to soil drought in the greenhouse. Native
      embolism and vulnerability to cavitation was measured in well-watered controls
      and after 5 d and 10 d of controlled drought. A dramatic cavitation fatigue was
      observed where droughted xylem that was refilled in the laboratory developed up
      to 60 PLC (percentage loss of hydraulic conductivity) at -1 MPa versus only 5.2
      PLC in non-droughted controls. Rewatered plants showed the complete reversal of
      cavitation fatigue over 4 d. Reversal of fatigue was correlated with the
      refilling of embolized vessels in the intact plants (r(2)=0.91, P<0.01),
      suggesting that xylem transport to fatigued vessels was required for their
      repair. The in vivo reversal of fatigue was partially duplicated in excised stem
      segments by perfusing them with root exudates from droughted (DR) and well
      watered (WW) plants. The DR exudate had a greater effect, and this was associated
      with a greater pH in the DR versus WW saps, but there was no difference in total
      cation concentration. Perfusions with 2 mM CaCl(2) and KCl solutions also
      partially reversed cavitation fatigue as opposed to no effect with deionized
      water, suggesting a role of ions in addition to a pH effect. It is suspected that
      fatigue is caused by stretching and partial disruption of linkages between
      cellulose microfibrils in inter-conduit pit membranes during air seeding, and
      that the reversal of fatigue involves restoring these linkages by ingredients in
      xylem sap.

PMID- 11971927
TI  - Phenotype/genotype associations for yield and salt tolerance in a barley mapping
      population segregating for two dwarfing genes.
AB  - Barley traits related to salt tolerance are mapped in a population segregating
      for a dwarfing gene associated with salt tolerance. Twelve quantitative trait
      loci (QTLs) were detected for seven seedling traits in doubled haploids from the
      spring barley cross Derkado x B83-12/21/5 when given saline treatment in
      hydroponics. The location of QTLs for seedling growth stage (leaf appearance
      rate), stem weight prior to elongation, and tiller number are reported for the
      first time. In addition, four QTLs were found for the mature plant traits grain
      nitrogen and plot yield. In total, seven QTLs are co-located with the dwarfing
      genes sdw1, on chromosome 3H, and ari-e.GP, on chromosome 5H, including seedling
      leaf response (SGa) to gibberellic acid (GA(3)). QTLs controlling the growth of
      leaves (GS2) on chromosomes 2H and 3H and emergence of tillers (TN2) and grain
      yield were independent of the dwarfing genes. Field trials were grown in eastern
      Scotland and England to estimate yield and grain composition. A genetic map was
      used to compare the positions of QTLs for seedling traits with the location of
      QTLs for the mature plant traits. The results are discussed in relation to the
      study of barley physiology and the location of genes for dwarf habit and
      responses to GA.

PMID- 11971928
TI  - Cadmium accumulation and buffering of cadmium-induced stress by arbuscular
      mycorrhiza in three Pisum sativum L. genotypes.
AB  - The role of arbuscular mycorrhiza in reducing Cd stress was investigated in three
      genotypes of Pisum sativum L. (cv. Frisson, VIR4788, VIR7128), grown in soil/sand
      pot cultures in the presence and absence of 2-3 mg kg(-1) bioavailable Cd, and
      inoculated or not with the arbuscular mycorrhizal fungus Glomus intraradices.
      Shoot, root and pod biomass were decreased by Cd in non-mycorrhizal plants. The
      presence of mycorrhiza attenuated the negative effect of Cd so that shoot biomass
      and activity of photosystem II, based on chlorophyll a fluorescence, were not
      significantly different between mycorrhizal plants growing in the presence or
      absence of the heavy metal (HM). Total P concentrations were not significantly
      different between mycorrhizal and non-mycorrhizal plants treated with Cd. From 20
      50-fold more Cd accumulated in roots than in shoots of Cd-treated plants, and
      overall levels were comparable to other metal-accumulating plants. Genetic
      variability in Cd accumulation existed between the pea genotypes. Concentration
      of the HM was lowest in roots of VIR4788 and in pods of VIR4788 and VIR7128. G.
      intraradices inoculation decreased Cd accumulation in roots and pods of cv.
      Frisson, whilst high concentrations were maintained in roots and pods of
      mycorrhizal VIR7128. Shoot concentrations of Cd increased in mycorrhizal cv.
      Frisson and VIR4788. Sequestration of Cd in root cell walls and/or cytoplasm,
      measured by EDS/SEM, was comparable between non-mycorrhizal pea genotypes but
      considerably decreased in mycorrhizal cv. Frisson and VIR7128. Possible
      mechanisms for mycorrhiza buffering of Cd-induced stress in the pea genotypes are
      discussed.

PMID- 11971929
TI  - Determining critical pre- and post-anthesis periods and physiological processes
      in Lycopersicon esculentum Mill. exposed to moderately elevated temperatures.
AB  - To determine the thermosensitive periods and physiological processes in tomato
      flowers exposed to moderately elevated temperatures, tomato plants (Lycopersicon
      esculentum Mill., cv. NC 8288) were grown at 28/22 degrees C or 32/26 degrees C
      day/night temperature regimes and then transferred to the opposite regime for 0
      15 d before or 0-24 h after anthesis. For plants initially grown at 28/22 degrees
      C, moderate temperature stress before anthesis decreased the percentage of fruit
      set per plant, but did not clarify the thermosensitive period. The same level of
      stress did not significantly reduce fruit set when applied immediately after
      anthesis. For plants initially grown at 32/26 degrees C, fruit set was completely
      prevented unless a relief period of more than 5 d was provided before anthesis.
      The same level of stress relief for 3-24 h after anthesis also increased fruit
      set. Plants were most sensitive to 32/26 degrees C temperatures 7-15 d before
      anthesis. Microscopic investigation of anthers in plants grown continuously at
      high temperature indicated disruption of development in the pollen, endothecium,
      epidermis, and stomium. This disruption was reduced, but still observable in
      plants relieved from high temperature for 10 d before anthesis.

PMID- 11971930
TI  - Two early light-inducible protein (ELIP) cDNAs from the resurrection plant
      Tortula ruralis are differentially expressed in response to desiccation,
      rehydration, salinity, and high light.
AB  - Tortula ruralis (Syntrichia ruralis) is a useful model system for the study of
      gene control in response to severe water deficit-stress. EST gene discovery
      efforts utilizing desiccated gametophytes have identified two cDNAs designated
      Elipa and Elipb with significant similarity to early light-inducible proteins
      (ELIPs). Elipa is 1006 bp in length, encoding a 212 amino acid deduced
      polypeptide (ELIPa) with a predicted molecular mass of 23.3 kDa and pI of 5.57.
      Elipb is 997 bp in length, encoding a 224 amino acid deduced polypeptide (ELIPb)
      with a predicted molecular mass of 24.4 kDa and pI of 9.27. Phylogenetic analysis
      demonstrated that ELIPa and ELIPb are reproducibly grouped with ELIP sequences
      derived from desiccation-tolerance tissues. RNA blot hybridization was used to
      analyse Elipa and Elipb mRNA abundance in response to a variety of stresses.
      Elipa steady-state transcript levels increased in response to slow desiccation,
      rapid desiccation/rehydration, salinity, ABA, and rehydration in high light. The
      Elipb transcript was only detectable in response to ABA or rehydration in high
      light. It is postulated that ELIPa and ELIPb are an adaptive response to stress
      induced photodamage within the moss chloroplast, and play a key role in the
      protection and/or repair of the photosynthetic apparatus.

PMID- 11971931
TI  - Arbuscular mycorrhiza infection enhances the growth response of Lolium perenne to
      elevated atmospheric pCO(2).
AB  - Elevated atmospheric pCO(2) increases the C-availability for plants and thus
      leads to a comparable increase in plant biomass production and nutrient demand.
      Arbuscular mycorrhizal fungi (AMF) are considered to play an important role in
      the nutrient uptake of plants as well as to be a significant C-sink. Therefore,
      an increased colonization of plant roots by AMF is expected under elevated
      atmospheric pCO(2). To test these hypotheses, Lolium perenne L. plants were grown
      from seeds in a growth chamber in pots containing a silica sand/soil mixture for
      9 weeks with and without inoculation with Glomus intraradices (Schenck and
      Smith). The growth response of plants at two different levels of N fertilization
      (1.5 or 4.5 mM) combined with ambient (35 Pa) and elevated atmospheric pCO(2) (60
      Pa) was compared. The inoculation with G. intraradices, the elevated atmospheric
      pCO(2) and the high N fertilization treatment all led to an increased plant
      biomass production of 16%, 20% and 49%, respectively. AMF colonization and high N
      fertilization increased the plant growth response to elevated atmospheric pCO(2);
      the plant growth response to high N fertilization was also increased by AMF
      colonization. The root/shoot ratio was reduced by high N fertilization or
      elevated atmospheric pCO(2), but was not affected by AMF colonization. The
      unchanged specific leaf area indicated that if AMF colonization represented an
      increased C-sink, this was fully covered by the plant. Elevated atmospheric
      pCO(2) strongly increased AMF colonization (60%) while the high N fertilization
      had a slightly negative effect. AMF colonization neither improved the N nor P
      nutrition status, but led to an improved total P uptake. The results underline
      the importance of AMF for the response of grassland ecosystems to elevated
      atmospheric pCO(2).

PMID- 11971932
TI  - Giant mitochondria are a response to low oxygen pressure in cells of tobacco
      (Nicotiana tabacum L.).
AB  - Low oxygen pressure induces fast and reversible formation of giant mitochondria
      in cells of Nicotiana tabacum. These can have unusual shapes, attain a length of
      80 microm and even form a reticulum. In contrast to animal cells, there is no
      such response to chemically induced oxidative stress.

PMID- 11971933
TI  - Cloning and expression of an ABSCISIC ACID-INSENSITIVE 3 (ABI3) gene homologue of
      yellow-cedar (Chamaecyparis nootkatensis).
AB  - A homologue of the ABI3 gene was isolated from the conifer species, Chamaecyparis
      nootkatensis. The deduced protein of 794 amino acids exhibited sequence
      similarity to other VP1/ABI3 proteins within four regions. Expression occurs
      exclusively in seeds, with no detectable mRNA in leaves and roots. Unlike the
      homologues of angiosperms, CnABI3 may be encoded by more than one gene.

PMID- 11971934
TI  - Characterization of two CTR-like protein kinases in Rosa hybrida and their
      expression during flower senescence and in response to ethylene.
AB  - The expression of two CTR-gene homologues was investigated during flower
      senescence in two Rosa hybrida cultivars. A fragment of a gene for a protein
      kinase, termed RhCTR1 (GenBank Acc. No. AF271206), was amplified by PCR and used
      to isolate the corresponding full-length cDNA (Acc. No. AY032953) from a rose
      petal cDNA library. The protein RhCTR1 has 66% amino acid identity to Arabidopsis
      CTR1. A fragment of a second CTR homologue, termed RhCTR2 (Acc. No. AY029067) is
      69% identical to the corresponding region of RhCTR1. RhCTR1 expression increased
      during flower senescence, while RhCTR2 was constitutively expressed during flower
      development. The expression of both RhCTR1 and RhCTR2 was increased in response
      to exogenous ethylene.

PMID- 11971935
TI  - 25R,26-Hydroxycholesterol revisited: synthesis, metabolism, and biologic roles.
AB  - The CYP27 gene is expressed in arterial endothelium, macrophages, and other
      tissues. The gene product generates sterol intermediates that function as ligands
      for nuclear receptors prior to their transport to the liver for metabolism,
      mostly to bile acids. Most attention has been given to 27-hydroxycholesterol as a
      ligand for LXR activated receptors and to chenodeoxycholic acid as a ligand for
      farnesoid X activated receptors (FXRs). Expression of the pathway in macrophages
      is essential for normal reverse cholesterol transport. Thus, ABC transporter
      activity is upregulated, which enhances cholesterol efflux. Absence of these
      mechanisms probably accounts for the accelerated atherosclerosis that occurs in
      cerebrotendinous xanthomatosis. Accumulation of 27-hydroxycholesterol in human
      atheroma is puzzling and may reflect low levels of oxysterol 7alpha-hydroxylase
      activity in human macrophages. The same enzyme determines the proportion of mono
      , di-, and tri-hydroxy bile acids synthesized in the liver. Oxysterol 7alpha
      hydroxylase deficiency is a molecular basis for cholestatic liver disease.
      Chenodeoxycholic acid, the major normal end product, downregulates expression of
      cholesterol 7alpha-hydroxylase via the FXR/short heterodimer protein nuclear
      receptor and thus limits total bile acid production. The challenge is to quantify
      in a physiologic setting the magnitude of the pathway in different tissues and to
      further evaluate the biologic roles of all the intermediates that may function as
      ligands for orphan nuclear receptors or via other regulatory mechanisms.

PMID- 11971936
TI  - Identification of mouse and human macrophages as a site of synthesis of hepatic
      lipase.
AB  - Hepatic lipase (HL) is synthesized by the liver and is also present in
      steroidogenic tissues. As both a lipolytic enzyme and a ligand that facilitates
      the cellular uptake of lipoproteins, HL plays a major role in lipoprotein
      metabolism and may modulate atherogenic risk. However, HL has not been directly
      implicated in lesion development. In the present study we demonstrate that HL is
      also synthesized by mouse and human macrophages. Northern analysis and real time
      RT-PCR showed that HL mRNA is present in mouse peritoneal macrophages, RAW-264.7,
      and IC-21 cells. The levels of HL mRNA in mouse peritoneal macrophages were
      approximately 10-30% that of mouse liver. HL protein was identified by Western
      blot analyses in human monocyte-derived macrophages, THP, RAW-264.7, and mouse
      peritoneal macrophages following fractionation by heparin-sepharose affinity
      chromatography. These combined findings establish that HL is synthesized de novo
      by macrophages as well as liver, and raises the possibility that HL may have a
      direct role in the pathogenesis of atherosclerosis.

PMID- 11971937
TI  - Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1
      fibroblasts to adipocytes.
AB  - The confluent cultures of 3T3-L1 fibroblasts were treated with or without
      bisphenol A (BPA) for 2 days and subsequently treated with insulin (INS) alone
      for 9 days. When BPA was absent during the first 2-day treatment period, the
      cultures contained 1.6 microg/microg DNA of triacylglycerol (TG), 202 mU/mg DNA
      of lipoprotein lipase (LPL) activity, and 462 nmol/min/mg DNA of glycerol-3
      phosphate dehydrogenase (GPDH) activity. The presence of BPA during the same
      period caused a 150% increase in the TG content, a 60% increase in the LPL
      activity, and a 500% increase in the GPDH activity. Thus, BPA by itself can
      trigger 3T3-L1 fibroblasts to differentiate into adipocytes. Next, the confluent
      cultures were treated with BPA for 2 days and subsequently treated with a
      combination of INS and BPA for 9 days. The simultaneous presence of BPA with INS
      caused a 370% increase in the TG content, a 200% increase in the LPL activity,
      and a 225% increase in the GPDH activity compared with the cultures treated with
      INS alone. The amount of [(3)H]thymidine incorporated into DNA was lower in the
      cultures treated with INS in the presence of BPA than in those treated with INS
      alone, indicating that BPA has an anti-proliferative activity on 3T3-L1 cells.
      Taken together, our results indicate that BPA in combination with INS can
      accelerate the adipocyte conversion.

PMID- 11971938
TI  - A novel primary bile acid in the Shoebill stork and herons and its phylogenetic
      significance.
AB  - The Shoebill stork, an enigma phylogenetically, was found to contain as its
      dominant biliary bile acid 16alpha-hydroxychenodeoxycholic acid, a heretofore
      undescribed bile acid. The bile acid occurred as its taurine N-acyl amidate;
      structure was established by nuclear magnetic resonance (NMR) and mass
      spectrometry (MS). A search for this novel bile acid in other Ciconiiformes
      showed that it constituted >92% of biliary bile acids in five of nine herons in
      the Ardidae, but was absent in all other families (Ciconiidae, Threskiornithidae,
      Scopidae, Phoenicopteridae). The presence of this biochemical trait in the
      Shoebill stork and certain herons suggests that these birds are closely related.

PMID- 11971939
TI  - Suppression of fatty acid synthase promoter by polyunsaturated fatty acids.
AB  - Dietary polyunsaturated fat is known to suppress expression of fatty acid
      synthase (FAS), a central enzyme in de novo lipogenesis. The sterol regulatory
      element-binding protein (SREBP) has recently been shown to be involved in this
      suppression. We previously reported that the first 2.1 kb of the FAS promoter are
      sufficient for transcriptional induction by a high carbohydrate diet as well as
      suppression by polyunsaturated fat in transgenic mice. Here, we first examined
      the DNA sequences responsible for SREBP-mediated suppression of FAS promoter
      activity by polyunsaturated fatty acids (PUFA) in vivo. Feeding polyunsaturated
      fat prevented both the low-level activation of the -278 FAS promoter which
      contains the -150 sterol response element (SRE), as well as the maximal
      activation of the longer -444 FAS promoter. We observed that ectopic expression
      of the activated form of SREBP in liver prevented PUFA-mediated suppression of
      both the endogenous FAS and FAS promoter-reporter transgene expression. We also
      found that the promoter region required for PUFA suppression in vivo is located
      between -278 to -131, where SREBP functions. Using HepG2 cells, we further
      examined the specific FAS promoter elements required for PUFA suppression. We
      found that the -150 SRE, as well as the -65 E-Box, contribute to PUFA suppression
      of the FAS promoter, at least in vitro.

PMID- 11971940
TI  - Density distribution of electronegative LDL in normolipemic and hyperlipemic
      subjects.
AB  - The density distribution of electronegative LDL [LDL(-)], a cytotoxic and
      inflammatory fraction of LDL present in plasma, was studied in 10 normolipemic
      (NL), 6 FH, and 11 hypertriglyceridemic (HTG) subjects. Six LDL subclasses of
      increased density (LDL1 to LDL6) were isolated by density-gradient
      ultracentrifugation (DGU). NL and FH subjects showed prevalence of light LDL,
      whereas HTG subjects showed prevalence of dense LDL. LDL(-) proportion was
      determined from total LDL or LDL-density subclasses by anion-exchange
      chromatography. LDL from FH patients had increased LDL(-) (35.1 +/- 9.9%)
      compared with LDL from NL and HTG subjects (9.4 +/- 2.3% and 12.3 +/- 4.3%,
      respectively). Most LDL(-) was contained in dense subclasses in NL (LDL4-6, 67.7
      +/- 3.1%) whereas most of LDL(-) from FH patients were contained in light LDL
      subclasses (LDL1-3) (86.2 +/- 1.6%). In these subjects, simvastatin therapy
      decreased LDL(-) to 28.2 +/- 6.7% and 21.2 +/- 5.6% at 3 and 6 months of
      treatment, respectively, due mainly to decreases in light LDL subclasses. In HTG
      subjects, half LDL(-) was contained in dense LDL subclasses (LDL4-6, 46.1 +/-
      2.0%). Non-denaturing acrylamide gradient gel electrophoresis concurred with DGU
      data, as LDL(-) from NL showed a single band of lower size than non
      electronegative LDL [LDL(+)], whereas LDL(-) from FH and HTG presented bands of
      greater size than its respective LDL(+). These results reveal the existence of
      light and dense LDL(-), indicate that hyperlipemia could promote the formation of
      light LDL(-) and suggest that LDL(-) could have different origins.

PMID- 11971942
TI  - Paraoxonase1-192 polymorphism modulates the effects of regular and acute exercise
      on paraoxonase1 activity.
AB  - Regular exercise practise is a protective factor against coronary heart disease
      and enhances antioxidant systems, whereas acute exercise appears to be a major
      source of increased oxidative stress. Paraoxonase1 (PON1) is an antioxidant HDL
      linked enzyme, whose activity toward paraoxon (PON1 activity) is strongly
      modulated by the PON1-192 polymorphism, comprising Q and R alleles for low and
      high PON1 activity, respectively. Another polymorphism at the PON1 locus, the
      PON1-55, modulates PON1 protein and activity levels. PON1 activity, lipid levels,
      and oxidized LDL concentration were determined in 17 healthy young volunteers
      before and after a 16-weeks aerobic exercise training period. Furthermore, PON1
      activity was analyzed after a bout of exercise in both situations. We found that
      regular exercise was associated with a decrease in oxidized LDL levels, and an
      increase in PON1 activity in QQ subjects and with a decrease in PON1 activity in
      R carriers. A bout of exercise produced an increase in PON1 activity just after
      the bout of exercise, followed by a decrease in its activity. A recovery of the
      basal PON1 activity levels at 24 h was found in QQ subjects regardless of their
      training status and in trained R carriers, but not in untrained R carriers. These
      results suggest that the effects of regular and acute exercise on PON1 activity
      levels are modulated by PON1-192 polymorphism. Changes were less evident for the
      PON1-55 polymorphism.

PMID- 11971941
TI  - Effect of atorvastatin on chylomicron remnant metabolism in visceral obesity: a
      study employing a new stable isotope breath test.
AB  - Elevated plasma concentration of chylomicron remnants may be causally related to
      atherosclerosis in obesity. We examined the effect of atorvastatin on chylomicron
      remnant metabolism in 25 obese men with dyslipidaemia. A remnant-like emulsion
      labeled with cholesteryl [(13)C]oleate was injected intravenously into patients;
      the fractional catabolic rate (FCR) of the remnant-like emulsion was determined
      by measurement of (13)CO(2) in the breath and analyzed using compartmental
      modelling. Compared with placebo, atorvastatin significantly decreased the plasma
      concentrations of total cholesterol, triglycerides, LDL cholesterol,
      apolipoprotein B (apoB), and lathosterol (P < 0.001). ApoB-48 and remnant-like
      particle-cholesterol (RLP-C) both decreased significantly by 23% (P = 0.002) and
      33% (P = 0.045), respectively. The FCR of the remnant-like emulsion increased
      significantly from 0.054 +/- 0.008 to 0.090 +/- 0.010 pools/h (P = 0.002). The
      decrease in RLP-C was associated with the decrease in plasma triglycerides (r =
      0.750, P = 0.003). Furthermore, the change in FCR of remnant-like emulsions was
      inversely associated with the change in LDL-C (r = -0.575, P = 0.040), suggesting
      removal of LDL and chylomicron remnants by similar hepatic receptor pathways. We
      conclude that in obese subjects, inhibition of cholesterol synthesis with
      atorvastatin decreases the plasma concentrations of both LDL-C and triglyceride
      rich remnants and that this may be partially due to an enhancement in hepatic
      clearance of these lipoproteins.

PMID- 11971943
TI  - Expression of key enzymes in bile acid biosynthesis during development: CYP7B1
      mediated activities show tissue-specific differences.
AB  - The developmental variation of cytochrome P450 (CYP)7A1, CYP7B1, CYP27A1, and
      3beta-hydroxy-Delta(5)-C(27)-steroid dehydrogenase, key enzymes in bile acid
      biosynthesis, were investigated in pigs of different ages. As part of these
      studies, peptide sequences from a purified pig liver oxysterol 7alpha-hydroxylase
      were analyzed. The sequences showed a high degree of identity with those of
      murine and human CYP7B1. Enzymatic activities and mRNA levels of CYP27A1 and
      3beta-hydroxy-Delta(5)-C(27)-steroid dehydrogenase were similar in livers of
      newborn and 6-month-old pigs. Enzymatic activity mediated by CYP7A1 increased
      several-fold between infancy and adolescence. Hepatic CYP7A1 and CYP7B1 mRNA
      levels increased several-fold with age. Hepatic microsomal 7alpha-hydroxylation
      of 27-hydroxycholesterol and dehydroepiandrosterone, substrates typical for
      CYP7B1, increased about 5-fold between infancy and adolescence whereas the
      activities in kidney microsomes decreased at least 10-fold. In conclusion, the
      results indicate that the expression of CYP27A1 and 3beta-hydroxy-Delta(5)-C(27)
      steroid dehydrogenase are similar in livers of newborn and 6-month-old pigs
      whereas the levels of CYP7A1 increase. The finding that the levels of CYP7B1
      increase with age in the liver but decrease in the kidney suggest a tissue
      specific developmental regulation of CYP7B1. The age-dependent variation in the
      liver and kidney suggests that hormonal factors are involved in the regulation of
      CYP7B1.

PMID- 11971944
TI  - Antioxidant properties of HDL in transgenic mice overexpressing human
      apolipoprotein A-II.
AB  - Transgenic mice overexpressing human apolipoprotein A-II (huapoA-II) display high
      VLDL and low HDL levels. To evaluate the antioxidant potential of huapoA-II
      enriched HDL, we measured the activities of paraoxonase (PON) and platelet
      activating factor acetylhydrolase (PAF-AH). Both activities decreased up to 43%
      in the serum of transgenic mice compared with controls, varied in parallel to HDL
      levels, but decreased less than HDL levels. The major part of PON and PAF-AH was
      associated with HDL, except in fed high huapoA-II-expressing mice, in which 20%
      of PAF-AH and 9% of PON activities were associated with VLDL. PON mRNA levels in
      the liver, its major site of synthesis, were similar in transgenic and control
      animals, indicating normal enzyme synthesis. In transgenic mice, the basal
      oxidation of lipoproteins was not increased, whereas their VLDL were more
      susceptible to oxidation than VLDL of controls. Interestingly, HDL of transgenic
      mice protected VLDL from oxidation more efficiently than HDL of controls. In
      conclusion, the decrease in both PON and PAF-AH activities in huapoA-II
      transgenic mice is best explained by their lower plasma HDL levels. However, the
      unchanged basal lipoprotein oxidation in transgenic mice suggests that huapoA-II
      rich HDL may maintain adequate antioxidant potential.

PMID- 11971946
TI  - 3-O-acetyl-sphingosine-series myelin glycolipids: characterization of novel 3-O
      acetyl-sphingosine galactosylceramide.
AB  - Several glycosphingolipids, less polar than galactosylceramide (GalCer), have
      been purified from rat brain and designated as fast migrating cerebrosides
      (FMCs). They co-appear with GalCer during myelinogenesis, reach a peak
      concentration at postnatal day 25-30 and are derivatives of GalCer. Extensive
      structural analysis of the partially methylated alditol acetates, mass
      spectrometry, and (1)H- and (13)C-nuclear magnetic resonance (NMR) spectroscopy
      unequivocally established the structure of two of these FMCs as 3-O-acetyl
      sphingosine GalCer with non-hydroxy and hydroxy fatty N-acylation respectively.
      That is, an acetyl group is linked at the C3-OH of the sphingosine base of
      GalCer. In addition, NMR spectroscopy of all of the purified FMCs indicates that
      they contain a 3-O-acetyl group linked with sphingosine and thus delineates a
      novel series. Several lines of evidence indicate that FMCs are myelin
      constituents. FMCs, enriched in both central nervous system (CNS) and peripheral
      nervous system (PNS) myelin, are concentrated in spinal cord and white matter
      that are composed of myelinated nerve fibers. There is N-acylation with alpha
      hydroxy and C18 and C24 fatty acids, all characteristic of myelin components.
      They disappear along with GalCer in the murine genetic dysmyelinating disorders,
      jimpy and quaking, and in a knockout mutant which is devoid of GalCer. In
      addition, a decrease in FMC and GalCer concentration has been found in Krabbe's
      disease, a human genetic dysmyelinating disorder.

PMID- 11971945
TI  - Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin
      resistance.
AB  - Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which
      potently regulates lipid homeostasis. Here we evaluate the ability of TTA to
      prevent diet-induced and genetically determined adiposity and insulin resistance.
      In Wistar rats fed a high fat diet, TTA administration completely prevented diet
      induced insulin resistance and adiposity. In genetically obese Zucker (fa/fa)
      rats TTA treatment reduced the epididymal adipose tissue mass and improved
      insulin sensitivity. All three rodent peroxisome proliferator-activated receptor
      (PPAR) subtypes were activated by TTA in the ranking order PPARalpha > PPARdelta
      > PPARgamma. Expression of PPARgamma target genes in adipose tissue was
      unaffected by TTA treatment, whereas the hepatic expression of PPARalpha
      responsive genes encoding enzymes involved in fatty acid uptake, transport, and
      oxidation was induced. This was accompanied by increased hepatic mitochondrial
      beta-oxidation and a decreased fatty acid/ketone body ratio in plasma. These
      findings indicate that PPARalpha-dependent mechanisms play a pivotal role, but
      additionally, the involvement of PPARalpha-independent pathways is conceivable.
      Taken together, our results suggest that a TTA-induced increase in hepatic fatty
      acid oxidation and ketogenesis drains fatty acids from blood and extrahepatic
      tissues and that this contributes significantly to the beneficial effects of TTA
      on fat mass accumulation and peripheral insulin sensitivity.

PMID- 11971947
TI  - Significant utilization of dietary arachidonic acid is for brain adrenic acid in
      baboon neonates.
AB  - Dietary arachidonic acid (20:4n-6) utilization in-vivo for carbon recycling into
      de-novo lipogenesis and conversion to n-6 long chain polyunsaturates was
      investigated in baboon neonates using [U-(13)C]20:4n-6. Neonates consuming a
      formula typical of human milk received a single oral dose of [(13)C]arachidonic
      acid in sn-2 position of either triglyceride or phosphatidylcholine at 18-19 days
      of postnatal life. Neonate brain, retina, liver, and plasma were obtained 10 days
      later (28-29 days of life). Low isotopic enrichment (0.27-1.0%Total label) was
      detected in dihomo-gamma-linolenic acid (20:3n-6) in all tissues, but label
      incorporation into saturates or monounsaturates was not detected. In neonate
      brain and retina, 16% and 11% of total label was recovered in 22:4n-6,
      respectively. The relative contribution of dietary fatty acids to postnatal brain
      22:4n-6 accretion can be estimated for dietary 20:4n-6 and preformed 22:4n-6 as
      17% and 8%, respectively, corresponding to efficiencies of 0.48% and 0.54% of
      dietary levels, respectively. These results demonstrate in term baboon neonates
      that in vivo 1) 20:4n-6 was retroconverted to 20:3n-6, 2) 20:4n-6 did not
      contribute significantly to de novo lipogenesis of saturates and monounsaturates,
      and 3) the preformed 20:4n-6 contribution to brain 22:4n-6 accumulation was
      quantitatively a significant metabolic fate for dietary 20:4n-6.

PMID- 11971948
TI  - Interleukin-4 deficiency promotes gallstone formation.
AB  - Feeding interleukin-4 (IL-4) deficient C57BL/6 LDL receptor (LDLr)(-/-) mice a
      modified diet to investigate the role of this cytokine in cholesterol metabolism
      led to an unexpected phenotype. IL-4(-/-) --> LDLr(-/-) mice had enlarged
      gallbladders and an increased mortality that was preceded by acute body weight
      loss. To determine if IL-4 deficiency accounted for these findings, C57BL/6 IL
      4(+/+) and IL-4(-/-) mice were fed either a normal or modified diet. IL-4
      deficiency did not alter bile composition or cause liver toxicity in mice fed a
      fat-enriched diet. Following 8 weeks of feeding a fat-enriched diet, no
      gallstones were detected in IL-4(+/+) mice, and only 20% had cholesterol
      crystals. In contrast, IL-4(-/-) mice had a 100% incidence of gallstones and
      cholesterol crystals. IL-4(-/-) deficiency also increased serum concentrations of
      bilirubin following feeding a fat-enriched diet. Therefore, these studies
      revealed an unexpected finding that IL-4 deficiency predisposes to gallstone
      formation.

PMID- 11971949
TI  - Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout
      mice.
AB  - We determined the effects of dietary n-6 and n-3 polyunsaturated fatty acids
      (PUFA) on parameters of plasma lipoprotein and hepatic lipid metabolism in LDL
      receptor (LDLr) knockout mice. Dietary n-3 PUFA decreased the rate of appearance
      and increased the hepatic clearance of IDL/LDL resulting in a marked decrease in
      the plasma concentration of these particles. Dietary n-3 PUFA increased the
      hepatic clearance of IDL/LDL through a mechanism that appears to involve
      apolipoprotein (apo)E but is independent of the LDLr, the LDLr related protein
      (LRP), the scavenger receptor B1, and the VLDLr. The decreased rate of appearance
      of IDL/VLDL in the plasma of animals fed n-3 PUFA could be attributed to a marked
      decrease in the plasma concentration of precursor VLDL. Decreased plasma VLDL
      concentrations were due in part to decreased hepatic secretion of VLDL
      triglyceride and cholesteryl esters, which in turn was associated with decreased
      concentrations of these lipids in liver. Decreased hepatic triglyceride
      concentrations in animals fed n-3 PUFA were due in part to suppression of fatty
      acid synthesis as a result of a decrease in sterol regulatory element binding
      protein-1 (SREBP-1) expression and processing. In conclusion, these studies
      indicate that n-3 PUFA can markedly decrease the plasma concentration of apoB
      containing lipoproteins and enhance hepatic LDL clearance through a mechanism
      that does not involve the LDLr pathway or LRP.

PMID- 11971950
TI  - Microsomal triglyceride transfer protein is essential for hepatic secretion of
      apoB-100 and apoB-48 but not triglyceride.
AB  - Despite a complete lack of microsomal triglyceride transfer protein (MTP), L35
      rat hepatoma cells secrete triglyceride-containing lipoproteins, albeit at a rate
      25% of that of parental FAO hepatoma cells, which express high levels of MTP. The
      inability to express MTP was associated with a complete block in the secretion of
      both apolipoprotein (apo)B-100 and apoB-48. Stable expression of a MTP transgene
      restored the secretion of both apoB-100 and apoB-48 in L35 cells, indicating that
      MTP is essential for the secretion of both forms of apoB. Treatment with the MTP
      inhibitor BMS-200150 reduced the secretion of triglyceride by 70% in FAO cells,
      whereas the inhibitor did not affect the secretion of triglycerides by L35 cells.
      Thus, in the presence of the MTP inhibitor, both cell types secreted
      triglycerides at similar rates. Essentially, all of the triglycerides secreted by
      L35 cells were associated with HDL containing apoA-IV and apoE but devoid of apoB
      100 or apoB-48. These results suggest that these triglyceride-containing
      lipoproteins are assembled and secreted via a pathway that is independent of both
      apoB and MTP. Our findings support the concept that apoB and MTP co-evolved and
      provided a means to augment the secretion of triglyceride through the formation
      of lipoproteins containing large hydrophobic cores enriched with triglycerides.

PMID- 11971951
TI  - Gas-chromatography/mass-spectrometry analysis of human skin constituents as
      heptafluorobutyrate derivatives with special reference to long-chain bases.
AB  - The composition of the constituents (monosaccharides, long-chain bases, and fatty
      acids) found in an ethanol extract of the human skin could be determined, without
      time-consuming steps of purification, after acid-catalyzed anhydrous
      methanolysis, followed by the formation of volatile derivatives with
      heptafluorobutyric anhydride and gas-chromatography/mass-spectrometry analysis.
      Despite the extreme heterogeneity of such extracts, the electron impact analysis
      of the constituents allowed qualitative and quantitative determinations of
      monosaccharides, long-chain bases, fatty acids, and alkyl-glycerols. Throughout
      the different long-chain bases, sphingenines (Sphes), sphinganines,
      phytosphingosines, and 6-hydroxy-Sphes (6oh-Sphes) can be identified and
      quantified. Long-chain bases with a chain-length up to 28 carbon atoms can be
      identified through specific fragmentation patterns in the electron impact mode.
      Particular attention was drawn to the behavior of compounds of the family of 6oh
      Sphes upon acid-catalyzed methanolysis.

PMID- 11971952
TI  - A new on-line dual enzymatic method for simultaneous quantification of
      cholesterol and triglycerides in lipoproteins by HPLC.
AB  - We describe an on-line dual detection method using HPLC for lipoprotein analysis
      that allows simultaneous determination of cholesterol and triglyceride profiles
      from a single injection of sample. Two different gel permeation columns, TSKgel
      LipopropakXL and Superose 6HR, were applied to the dual detection system,
      evaluating analytical performance of the proposed method and the columns by
      analyzing serum samples from human and nonhuman subjects. Both TSK and Superose
      columns produced good within-day imprecision values less than 4.7% for
      cholesterol and 4.2% for triglyceride determination. Linear regression analysis
      showed the results from the Superose column (y) correlated well with those from
      the TSK column (x): y = 0.969x + 5.44 (r = 0.990) for total cholesterol (mg/dl),
      y = 1.08x - 11.14 (r = 0.985) for total triglycerides (mg/dl), and y = 1.093x -
      0.06 (r = 0.978) for the ratios of triglycerides to cholesterol (mg/mg).
      Furthermore, the cholesterol and triglyceride profiles elucidated the differences
      in the resolution ability of the columns, which have not been apparent from a
      single lipid profile. We conclude that the dual detection concept with proper
      choice of column and enzymic reagents specific to the objectives of the
      particular study can facilitate studies of lipoprotein metabolism.

PMID- 11971954
TI  - Rapid isolation of VLDL subfractions: assessment of composition and
      susceptibility to copper-mediated oxidation.
AB  - VLDLs, synthesized and released by the liver, are a heterogeneous group of
      particles of varying composition and metabolic fates. A method is described for
      the rapid isolation of VLDL into four subfractions (A-D) and assessment of their
      susceptibility to oxidation. The total isolation procedure required less than 3.5
      h, and was achieved by gradient ultracentrifugation. Each subfraction was
      assessed for triglyceride, cholesterol, and apolipoprotein B (apoB) composition
      and for the presence of contaminants such as albumin and urate. The oxidation
      potential, in the presence of copper ions, of each subfraction was also assessed.
      This rapid procedure produced VLDL fractions analogous to those produced by a
      previously reported but more prolonged isolation method. Comparison of the two
      procedures demonstrated that lipid and apoB were similar, while the rapid
      procedure produced subfractions void of albumin and urate contamination and lower
      in preformed hydroperoxides. Compositional changes were found between the
      subfractions: as the subfractions became smaller and more dense (A-->D), there
      was a decrease in the ratio of triglyceride to apoB and an increase in the ratio
      of cholesterol to apoB, also arachidonic acid was increased in subfraction D
      compared with subfractions A, B, and C. The smaller subfractions were more
      susceptible to oxidation, a trend similar to that reported previously for the
      oxidation of LDL subfractions.

PMID- 11971953
TI  - High-precision fluorescence assay for sphingomyelinase activity of isolated
      enzymes and cell lysates.
AB  - Sphingomyelinases are important enzymes of signal transduction. They catalyze the
      hydrolysis of sphingomyelin, giving rise to the intracellular formation of
      biologically active ceramide and phosphatidylcholine. Here we report on a
      fluorescence method for the fast and accurate determination of this enzyme in
      biological samples. The assay is based on a fluorescent sphingomyelin analog
      carrying fluorescent 7-nitro-2-1,3-benzooxadiazolyl amino-dodecanoic acid instead
      of an aliphatic acyl chain at the nitrogen atom. The fluorescent substrate is
      hydrolysed by sphingomyelinases to form fluorescent ceramide, which can be
      separated from the remaining substrate using TLC on silica gel. The fluorescence
      intensity pattern obtained on the TLC plate can accurately be determined using a
      CCD camera. Typically, a large number of samples can be analyzed simultaneously.
      Examples for the quantitative analysis of sphingomyelinases from freshly prepared
      cellular homogenates as well as from commercial sources are given.

PMID- 11971955
TI  - Human U4/U6.U5 and U4atac/U6atac.U5 tri-snRNPs exhibit similar protein
      compositions.
AB  - In the U12-dependent spliceosome, the U4atac/U6atac snRNP represents the
      functional analogue of the major U4/U6 snRNP. Little information is available
      presently regarding the protein composition of the former snRNP and its
      association with other snRNPs. In this report we show that human U4atac/U6atac di
      snRNPs associate with U5 snRNPs to form a 25S U4atac/U6atac.U5 trimeric particle.
      Comparative analysis of minor and major tri-snRNPs by using immunoprecipitation
      experiments revealed that their protein compositions are very similar, if not
      identical. Not only U5-specific proteins but, surprisingly, all tested U4/U6- and
      major tri-snRNP-specific proteins were detected in the minor tri-snRNP complex.
      Significantly, the major tri-snRNP-specific proteins 65K and 110K, which are
      required for integration of the major tri-snRNP into the U2-dependent
      spliceosome, were among those proteins detected in the minor tri-snRNP, raising
      an interesting question as to how the specificity of addition of tri-snRNP to the
      corresponding spliceosome is maintained. Moreover, immunodepletion studies
      demonstrated that the U4/U6-specific 61K protein, which is involved in the
      formation of major tri-snRNPs, is essential for the association of the
      U4atac/U6atac di-snRNP with U5 to form the U4atac/U6atac.U5 tri-snRNP. Subsequent
      immunoprecipitation studies demonstrated that those proteins detected in the
      minor tri-snRNP complex are also incorporated into U12-dependent spliceosomes.
      This remarkable conservation of polypeptides between minor and major
      spliceosomes, coupled with the absence of significant sequence similarity between
      the functionally analogous snRNAs, supports an evolutionary model in which most
      major and minor spliceosomal proteins, but not snRNAs, are derived from a common
      ancestor.

PMID- 11971956
TI  - Grap negatively regulates T-cell receptor-elicited lymphocyte proliferation and
      interleukin-2 induction.
AB  - Grb-2-related adaptor protein (Grap) is a Grb2-like SH3-SH2-SH3 adaptor protein
      with expression restricted to lymphoid tissues. Grap(-/-) lymphocytes isolated
      from targeted Grap-deficient mice exhibited enhanced proliferation, interleukin-2
      production, and c-fos induction in response to mitogenic T-cell receptor (TCR)
      stimulation, compared to wild-type cells. Ectopic expression of Grap led to a
      suppression of Elk-1-directed transcription induced by the Ras/Erk pathway,
      without having effects on gene expression mediated by Jnk and p38 mitogen
      activated protein kinases. Together, these data suggest that Grap, unlike Grb2,
      acts as a negative regulator of TCR-stimulated intracellular signaling by
      downregulating signal relay through the Ras/Erk pathway.

PMID- 11971958
TI  - p53 Binds and activates the xeroderma pigmentosum DDB2 gene in humans but not
      mice.
AB  - The DDB2 gene, which is mutated in xeroderma pigmentosum group E, enhances global
      genomic repair of cyclobutane pyrimidine dimers and suppresses UV-induced
      mutagenesis. Because DDB2 transcription increases after DNA damage in a p53
      dependent manner, we searched for and found a region in the human DDB2 gene that
      binds and responds transcriptionally to p53. The corresponding region in the
      mouse DDB2 gene shared significant sequence identity with the human gene but was
      deficient for p53 binding and transcriptional activation. Furthermore, when mouse
      cells were exposed to UV, DDB2 transcription remained unchanged, despite the
      accumulation of p53 protein. These results demonstrate direct activation of the
      human DDB2 gene by p53. They also explain an important difference in DNA repair
      between humans and mice and show how mouse models can be improved to better
      reflect cancer susceptibility in humans.

PMID- 11971957
TI  - Cyclic AMP-dependent kinase regulates Raf-1 kinase mainly by phosphorylation of
      serine 259.
AB  - The Raf-1 kinase activates the ERK (extracellular-signal-regulated kinase)
      pathway. The cyclic AMP (cAMP)-dependent protein kinase (PKA) can inhibit Raf-1
      by direct phosphorylation. We have mapped all cAMP-induced phosphorylation sites
      in Raf-1, showing that serines 43, 259, and 621 are phosphorylated by PKA in
      vitro and induced by cAMP in vivo. Serine 43 phosphorylation decreased the
      binding to Ras in serum-starved but not in mitogen-stimulated cells. However, the
      kinase activity of a RafS43A mutant was fully inhibited by PKA. Mutation of
      serine 259 increased the basal Raf-1 activity and rendered it largely resistant
      to inhibition by PKA. cAMP increased Raf-1 serine 259 phosphorylation in a PKA
      dependent manner with kinetics that correlated with ERK deactivation. PKA also
      decreased Raf-1 serine 338 phosphorylation of Raf-1, previously shown to be
      required for Raf-1 activation. Serine 338 phosphorylation of a RafS259A mutant
      was unaffected by PKA. Using RafS259 mutants we also demonstrate that Raf-1 is
      the sole target for PKA inhibition of ERK and ERK-induced gene expression, and
      that Raf-1 inhibition is mediated mainly through serine 259 phosphorylation.

PMID- 11971959
TI  - ATP-dependent mobilization of the glucocorticoid receptor during chromatin
      remodeling.
AB  - Chromatin remodeling by the glucocorticoid receptor (GR) is associated with
      activation of transcription at the mouse mammary tumor virus (MMTV) promoter. We
      reconstituted this nucleoprotein transition with chromatin assembled on MMTV DNA.
      The remodeling event was ATP dependent and required either a nuclear extract from
      HeLa cells or purified human Swi/Snf. Through the use of a direct interaction
      assay (magnetic bead pull-down), we demonstrated recruitment of human Swi/Snf to
      MMTV chromatin by GR. Unexpectedly, we found that GR is actively displaced from
      the chromatin template during the remodeling process. ATP-dependent GR
      displacement was reversed by the addition of apyrase and was specific to
      chromatin templates. The disengagement reaction could also be induced with
      purified human Swi/Snf. Although GR apparently dissociated during chromatin
      remodeling by Swi/Snf, it participated in binding of the secondary transcription
      factor, nuclear factor 1. These results are paralleled by a recent discovery that
      the hormone-occupied receptor undergoes rapid exchange between chromatin and the
      nucleoplasmic compartment in living cells. Both the in vitro and in vivo results
      are consistent with a dynamic model (hit and run) in which GR first binds to
      chromatin after ligand activation, recruits a remodeling activity, facilitates
      transcription factor binding, and is simultaneously lost from the template.

PMID- 11971960
TI  - Essential roles of Bdp1, a subunit of RNA polymerase III initiation factor
      TFIIIB, in transcription and tRNA processing.
AB  - The essential Saccharomyces cerevisiae gene BDP1 encodes a subunit of RNA
      polymerase III (Pol III) transcription factor (TFIIIB); TATA box binding protein
      (TBP) and Brf1 are the other subunits of this three-protein complex. Deletion
      analysis defined three segments of Bdp1 that are essential for viability. A
      central segment, comprising amino acids 327 to 353, was found to be dispensable,
      and cells making Bdp1 that was split within this segment, at amino acid 352, are
      viable. Suppression of bdp1 conditional viability by overexpressing SPT15 and
      BRF1 identified functional interactions of specific Bdp1 segments with TBP and
      Brf1, respectively. A Bdp1 deletion near essential segment I was synthetically
      lethal with overexpression of PCF1-1, a dominant gain-of-function mutation in the
      second tetracopeptide repeat motif (out of 11) of the Tfc4 (tau(131)) subunit of
      TFIIIC. The analysis also identifies a connection between Bdp1 and
      posttranscriptional processing of Pol III transcripts. Yeast genomic library
      screening identified RPR1 as the specific overexpression suppressor of very slow
      growth at 37 degrees C due to deletion of Bdp1 amino acids 253 to 269. RPR1 RNA,
      a Pol III transcript, is the RNA subunit of RNase P, which trims pre-tRNA
      transcript 5' ends. Maturation of tRNA was found to be aberrant in bdp1-Delta 253
      269 cells, and RPR1 transcription with the highly resolved Pol III transcription
      system in vitro was also diminished when recombinant Bdp1 Delta 253-269 replaced
      wild-type Bdp1. Physical interaction of RNase P with Bdp1 was demonstrated by
      coimmunoprecipitation and pull-down assays.

PMID- 11971961
TI  - A testicular germ cell-associated serine-threonine kinase, MAK, is dispensable
      for sperm formation.
AB  - A member of the mitogen-activated protein kinase superfamily, MAK, has been
      proposed to have an important role in spermatogenesis, since Mak gene expression
      is highly restricted to testicular germ cells. To assess the biological function
      of MAK, we have established MAK-deficient (Mak(-/-)) mice. Mak(-/-) mice
      developed normally, and no gross abnormalities were observed. Spermatogenesis of
      the Mak(-/-) mice was also intact, and most of the mice were fertile. However,
      Mak(-/-) male-derived litter sizes and their sperm motility in vitro were mildly
      reduced. These data show that function of MAK is not essential for
      spermatogenesis and male fertility.

PMID- 11971962
TI  - Saccharomyces cerevisiae Mer3 is a DNA helicase involved in meiotic crossing
      over.
AB  - Crossing over is regulated to occur at least once per each pair of homologous
      chromosomes during meiotic prophase to ensure proper segregation of chromosomes
      at the first meiotic division. In a mer3 deletion mutant of Saccharomyces
      cerevisiae, crossing over is decreased, and the distribution of the crossovers
      that occur is random. The predicted Mer3 protein contains seven motifs
      characteristic of the DExH box type of DNA/RNA helicases. The mer3G166D and the
      mer3K167A mutation, amino acid substitutions of conserved residues in a putative
      nucleotide-binding domain of the helicase motifs caused a defect in the
      transition of meiosis-specific double-strand breaks to later intermediates,
      decreased crossing over, and reduced crossover interference. The purified Mer3
      protein was found to have DNA helicase activity. This helicase activity was
      reduced by the mer3GD mutation to <1% of the wild-type activity, even though
      binding of the mutant protein to single- and double-strand DNA was unaffected.
      The mer3KA mutation eliminated the ATPase activity of the wild-type protein.
      These results demonstrate that Mer3 is a DNA helicase that functions in meiotic
      crossing over.

PMID- 11971963
TI  - c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to
      DNA damage.
AB  - The ubiquitously expressed c-Abl tyrosine kinase is activated in the apoptotic
      response of cells to DNA damage. The mechanisms by which c-Abl signals the
      induction of apoptosis are not understood. Here we show that c-Abl binds
      constitutively to the mammalian homolog of the Schizosaccharomyces pombe Rad9
      cell cycle checkpoint protein. The SH3 domain of c-Abl interacts directly with
      the C-terminal region of Rad9. c-Abl phosphorylates the Rad9 Bcl-2 homology 3
      domain (Tyr-28) in vitro and in cells exposed to DNA-damaging agents. The results
      also demonstrate that c-Abl-mediated phosphorylation of Rad9 induces binding of
      Rad9 to the antiapototic Bcl-x(L) protein. The regulation of Rad9 by c-Abl in the
      DNA damage response is further supported by the demonstration that the
      interaction between c-Abl and Rad9 contributes to DNA damage-induced apoptosis.
      These findings indicate that Rad9 is regulated by a c-Abl-dependent mechanism in
      the apoptotic response to genotoxic stress.

PMID- 11971965
TI  - Regulation of Jak2 through the ubiquitin-proteasome pathway involves
      phosphorylation of Jak2 on Y1007 and interaction with SOCS-1.
AB  - The family of cytoplasmic Janus (Jak) tyrosine kinases plays an essential role in
      cytokine signal transduction, regulating cell survival and gene expression.
      Ligand-induced receptor dimerization results in phosphorylation of Jak2 on
      activation loop tyrosine Y1007 and stimulation of its catalytic activity, which,
      in turn, results in activation of several downstream signaling cascades.
      Recently, the catalytic activity of Jak2 has been found to be subject to negative
      regulation through various mechanisms including association with SOCS proteins.
      Here we show that the ubiquitin-dependent proteolysis pathway is involved in the
      regulation of the turnover of activated Jak2. In unstimulated cells Jak2 was
      monoubiquitinated, and interleukin-3 or gamma interferon stimulation induced
      polyubiquitination of Jak2. The polyubiquitinated Jak2 was rapidly degraded
      through proteasomes. By using different Jak2 mutants we show that tyrosine
      phosphorylated Jak2 is preferentially polyubiquitinated and degraded.
      Furthermore, phosphorylation of Y1007 on Jak2 was required for proteasomal
      degradation and for SOCS-1-mediated downregulation of Jak2. The proteasome
      inhibitor treatment stabilized the Jak2-SOCS-1 protein complex and inhibited the
      proteolysis of Jak2. In summary, these results indicate that the ubiquitin
      proteasome pathway negatively regulates tyrosine-phosphorylated Jak2 in cytokine
      receptor signaling, which provides an additional mechanism to control activation
      of Jak2 and maintain cellular homeostasis.

PMID- 11971964
TI  - Poly(A)-binding protein acts in translation termination via eukaryotic release
      factor 3 interaction and does not influence [PSI(+)] propagation.
AB  - Recent studies of translational control suggest that translation termination may
      not be simply the end of synthesizing a protein but rather be involved in
      modulating both the translation efficiency and stability of a given transcript.
      Using recombinant eukaryotic release factor 3 (eRF3) and cellular extracts, we
      have shown for Saccharomyces cerevisiae that yeast eRF3 and Pab1p can interact.
      This interaction, mediated by the N+M domain of eRF3 and amino acids 473 to 577
      of Pab1p, was demonstrated to be direct by the two-hybrid approach. We confirmed
      that a genetic interaction exists between eRF3 and Pab1p and showed that Pab1p
      overexpression enhances the efficiency of termination in SUP35 (eRF3) mutant and
      [PSI(+)] cells. This effect requires the interaction of Pab1p with eRF3. These
      data further strengthen the possibility that Pab1p has a role in coupling
      translation termination events with initiation of translation. Several lines of
      evidence indicate that Pab1p does not influence [PSI(+)] propagation. First,
      "[PSI(+)]-no-more" mutations do not affect eRF3-Pab1p two-hybrid interaction.
      Second, overexpression of PAB1 does not cure the [PSI(+)] phenotype or solubilize
      detectable amounts of eRF3. Third, prion-curing properties of overexpressed
      HSP104p, which is required for formation and maintenance of [PSI(+)], were not
      modified by excess Pab1p.

PMID- 11971967
TI  - Multiple nucleosome positioning sites regulate the CTCF-mediated insulator
      function of the H19 imprinting control region.
AB  - The 5' region of the H19 gene harbors a methylation-sensitive chromatin insulator
      within an imprinting control region (ICR). Insertional mutagenesis in combination
      with episomal assays identified nucleosome positioning sequences (NPSs) that set
      the stage for the remarkably precise distribution of the four target sites for
      the chromatin insulator protein CTCF to nucleosome linker sequences in the H19
      ICR. Changing positions of the NPSs resulted in loss of both CTCF target site
      occupancy and insulator function, suggesting that the NPSs optimize the fidelity
      of the insulator function. We propose that the NPSs ensure the fidelity of the
      repressed status of the maternal Igf2 allele during development by constitutively
      maintaining availability of the CTCF target sites.

PMID- 11971966
TI  - Physical interaction of human T-cell leukemia virus type 1 Tax with cyclin
      dependent kinase 4 stimulates the phosphorylation of retinoblastoma protein.
AB  - The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1) induces
      leukemia in transgenic mice and permanent T-cell growth in vitro. In transformed
      lymphocytes, it acts as an essential growth factor. Tax stimulates the cell cycle
      in the G(1) phase by activating the cyclin-dependent kinase (CDK) CDK4 and CDK6
      holoenzyme complexes. Here we show that Tax directly interacts with CDK4. This
      binding to CDK4 was specific, since Tax did not bind to either CDK2 or CDK1. The
      interaction with CDK4/cyclin D complexes was observed in vitro, in transfected
      fibroblasts, in HTLV-1-infected T cells, and in adult T-cell leukemia-derived
      cultures. Binding studies with several point and deletion mutants indicated that
      the N terminus of Tax mediates the interaction with CDK4. The Tax/CDK complex
      represented an active holoenzyme which capably phosphorylates the Rb protein in
      vitro and is resistant to repression by the inhibitor p21(CIP). Binding-deficient
      Tax mutants failed to activate CDK4, indicating that direct association with Tax
      is required for enhanced kinase activity. Tax also increased the association of
      CDK4 with its positive cyclin regulatory subunit. Thus, protein-protein contact
      between Tax and the components of the cyclin D/CDK complexes provides a further
      mechanistic explanation for the mitogenic and immortalizing effects of this HTLV
      1 oncoprotein.

PMID- 11971968
TI  - mRTVP-1, a novel p53 target gene with proapoptotic activities.
AB  - We identified a novel mouse gene, mRTVP-1, as a p53 target gene using
      differential display PCR and extensive promoter analysis. The mRTVP-1 protein has
      255 amino acids and differs from the human RTVP-1 (hRTVP-1) protein by two short
      in-frame deletions of two and nine amino acids. RTVP-1 mRNA was induced in
      multiple cancer cell lines by adenovirus-mediated delivery of p53 and by gamma
      irradiation or doxorubicin both in the presence and in the absence of endogenous
      p53. Analysis of RTVP-1 expression in nontransformed and transformed cells
      further supported p53-independent gene regulation. Using luciferase reporter and
      electrophoretic mobility shift assays we identified a p53 binding site within
      intron 1 of the mRTVP-1 gene. Overexpression of mRTVP-1 or hRTVP-1 induced
      apoptosis in multiple cancer cell lines including prostate cancer cell lines 148
      1PA, 178-2BMA, PC-3, TSU-Pr1, and LNCaP, a human lung cancer cell line, H1299,
      and two isogenic human colon cancer cell lines, HCT116 p53(+/+) and HCT116 p53(-/
      ), as demonstrated by annexin V positivity, phase-contrast microscopy, and in
      selected cases 4',6'-diamidino-2-phenylindole staining and DNA fragmentation.
      Deletion of the signal peptide from the N terminus of RTVP-1 reduced its
      apoptotic activities, suggesting that a secreted and soluble form of RTVP-1 may
      mediate, in part, its proapoptotic activities.

PMID- 11971969
TI  - ERAP140, a conserved tissue-specific nuclear receptor coactivator.
AB  - We report here the identification and characterization of a novel nuclear
      receptor coactivator, ERAP140. ERAP140 was isolated in a screen for ER alpha
      interacting proteins using the ER alpha ligand binding domain as a probe. The
      ERAP140 protein shares no sequence and has little structural homology with other
      nuclear receptor cofactors. However, homologues of ERAP140 have been identified
      in mouse, Drosophila, and Caenorhabditis elegans. The expression of ERAP140 is
      cell and tissue type specific and is most abundant in the brain, where its
      expression is restricted to neurons. In addition to interacting with ER alpha,
      ERAP140 also binds ER beta, TR beta, PPAR gamma, and RAR alpha. ERAP140 interacts
      with ER alpha via a noncanonical interaction motif. The ER alpha-ERAP140
      association can be competed by coactivator NR boxes, indicating ERAP140 binds ER
      alpha on a surface similar to that of other coactivators. ERAP140 can enhance the
      transcriptional activities of nuclear receptors with which it interacts. In vivo,
      ERAP140 is recruited by estrogen-bound ER alpha to the promoter region of
      endogenous ER alpha target genes. Furthermore, the E(2)-induced recruitment of
      ERAP140 to the promoter follows a cyclic pattern similar to that of other
      coactivators. Our results suggest that ERAP140 represents a distinct class of
      nuclear receptor coactivators that mediates receptor signaling in specific target
      tissues.

PMID- 11971970
TI  - Androgen receptor acetylation governs trans activation and MEKK1-induced
      apoptosis without affecting in vitro sumoylation and trans-repression function.
AB  - The androgen receptor (AR) is a nuclear hormone receptor superfamily member that
      conveys both trans repression and ligand-dependent trans-activation function.
      Activation of the AR by dihydrotestosterone (DHT) regulates diverse physiological
      functions including secondary sexual differentiation in the male and the
      induction of apoptosis by the JNK kinase, MEKK1. The AR is posttranslationally
      modified on lysine residues by acetylation and sumoylation. The histone
      acetylases p300 and P/CAF directly acetylate the AR in vitro at a conserved KLKK
      motif. To determine the functional properties governed by AR acetylation, point
      mutations of the KLKK motif that abrogated acetylation were engineered and
      examined in vitro and in vivo. The AR acetylation site point mutants showed wild
      type trans repression of NF-kappa B, AP-1, and Sp1 activity; wild-type
      sumoylation in vitro; wild-type ligand binding; and ligand-induced conformational
      changes. However, acetylation-deficient AR mutants were selectively defective in
      DHT-induced trans activation of androgen-responsive reporter genes and
      coactivation by SRC1, Ubc9, TIP60, and p300. The AR acetylation site mutant
      showed 10-fold increased binding of the N-CoR corepressor compared with the AR
      wild type in the presence of ligand. Furthermore, histone deacetylase 1 (HDAC1)
      bound the AR both in vivo and in cultured cells and HDAC1 binding to the AR was
      disengaged in a DHT-dependent manner. MEKK1 induced AR-dependent apoptosis in
      prostate cancer cells. The AR acetylation mutant was defective in MEKK1-induced
      apoptosis, suggesting that the conserved AR acetylation site contributes to a
      pathway governing prostate cancer cellular survival. As AR lysine residue
      mutations that abrogate acetylation correlate with enhanced binding of the N-CoR
      repressor in cultured cells, the conserved AR motif may directly or indirectly
      regulate ligand-dependent corepressor disengagement and, thereby, ligand
      dependent trans activation.

PMID- 11971972
TI  - Low-molecular-weight protein tyrosine phosphatase is a positive component of the
      fibroblast growth factor receptor signaling pathway.
AB  - Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) has been implicated
      in the regulation of cell growth and actin rearrangement mediated by several
      receptor tyrosine kinases, including platelet-derived growth factor and epidermal
      growth factor. Here we identify the Xenopus laevis homolog of LMW-PTP1 (XLPTP1)
      as an additional positive regulator in the fibroblast growth factor (FGF)
      signaling pathway during Xenopus development. XLPTP1 has an expression pattern
      that displays substantial overlap with FGF receptor 1 (FGFR1) during Xenopus
      development. Using morpholino antisense technology, we show that inhibition of
      endogenous XLPTP1 expression dramatically restricts anterior and posterior
      structure development and inhibits mesoderm formation. In ectodermal explants,
      loss of XLPTP1 expression dramatically blocks the induction of the early mesoderm
      gene, Xbrachyury (Xbra), by FGF and partially blocks Xbra induction by Activin.
      Moreover, FGF-induced activation of mitogen-activated protein (MAP) kinase is
      also inhibited by XLPTP1 morpholino antisense oligonucleotides; however,
      introduction of RNA encoding XLPTP1 is able to rescue morphological and
      biochemical effects of antisense inhibition. Inhibition of FGF-induced MAP kinase
      activity due to loss of XLPTP1 is also rescued by an active Ras, implying that
      XLPTP1 may act upstream of or parallel to Ras. Finally, XLPTP1 physically
      associates only with an activated FGFR1, and this interaction requires the
      presence of SNT1/FRS-2 (FGFR substrate 2). Although LMW-PTP1 has been shown to
      participate in other receptor systems, the data presented here also reveal XLPTP1
      as a new and important component of the FGF signaling pathway.

PMID- 11971971
TI  - Sequential activation of the MEK-extracellular signal-regulated kinase and MKK3/6
      p38 mitogen-activated protein kinase pathways mediates oncogenic ras-induced
      premature senescence.
AB  - In primary mammalian cells, oncogenic ras induces premature senescence, depending
      on an active MEK-extracellular signal-regulated kinase (ERK) mitogen-activated
      protein kinase (MAPK) pathway. It has been unclear how activation of the
      mitogenic MEK-ERK pathway by ras can confer growth inhibition. In this study, we
      have found that the stress-activated MAPK, p38, is also activated during the
      onset of ras-induced senescence in primary human fibroblasts. Constitutive
      activation of p38 by active MKK3 or MKK6 induces senescence. Oncogenic ras fails
      to provoke senescence when p38 activity is inhibited, suggesting that p38
      activation is essential for ras-induced senescence. Furthermore, we have
      demonstrated that p38 activity is stimulated by ras as a result of an activated
      MEK-ERK pathway. Following activation of MEK and ERK, expression of oncogenic ras
      leads to the accumulation of active MKK3/6 and p38 activation in a MEK-dependent
      fashion and subsequently induces senescence. Active MEK1 induces the same set of
      changes and provokes senescence relying on active p38. Therefore, oncogenic ras
      provokes premature senescence by sequentially activating the MEK-ERK and MKK3/6
      p38 pathways in normal, primary cells. These studies have defined the molecular
      events within the ras signaling cascade that lead to premature senescence and,
      thus, have provided new insights into how ras confers oncogenic transformation in
      primary cells.

PMID- 11971973
TI  - Hsp72 and stress kinase c-jun N-terminal kinase regulate the bid-dependent
      pathway in tumor necrosis factor-induced apoptosis.
AB  - The major inducible heat shock protein Hsp72 has been shown to protect cells from
      certain apoptotic stimuli. Here we investigated the mechanism of Hsp72-mediated
      protection from tumor necrosis factor (TNF)-induced apoptosis of primary culture
      of IMR90 human fibroblasts. Hsp72 temporarily blocked apoptosis in response to
      TNF and permanently protected cells from heat shock. An Hsp72 mutant (Hsp72 Delta
      EEVD) with a deletion of the four C-terminal amino acids, which are essential for
      the chaperone function, blocked TNF-induced apoptosis in a manner similar to that
      of normal Hsp72 but did not inhibit heat shock-induced death. Therefore, the
      chaperone activity of Hsp72 is dispensable for suppression of TNF-induced
      apoptosis but is required for protection from heat shock. In fibroblasts derived
      from Bid knockout mice, similar temporal inhibition of TNF-induced apoptosis was
      seen. In these cells neither normal Hsp72 nor Hsp72 Delta EEVD conferred
      additional protection from apoptosis, suggesting that Hsp72 specifically affects
      Bid-dependent but not Bid-independent apoptotic pathways. Furthermore, both
      normal Hsp72 and Delta Hsp72EEVD inhibited Bid activation and downstream events,
      including release of cytochrome c, activation of caspase 3, and cleavage of poly
      ADP-ribose polymerase. Both Hsp72 and Delta Hsp72EEVD blocked activation of the
      stress kinase c-jun N-terminal kinase (JNK) by TNF, and specific inhibition of
      JNK similarly temporarily blocked Bid activation and the downstream apoptotic
      events. These data strongly suggest that in TNF-induced apoptosis, Hsp72
      specifically interferes with the Bid-dependent apoptotic pathway via inhibition
      of JNK.

PMID- 11971974
TI  - AMP-activated kinase regulates cytoplasmic HuR.
AB  - While transport of RNA-binding protein HuR from nucleus to cytoplasm is emerging
      as a key regulatory step for HuR function, the mechanisms underlying this process
      remain poorly understood. Here, we report that the AMP-activated kinase (AMPK),
      an enzyme involved in responding to metabolic stresses, potently regulates the
      levels of cytoplasmic HuR. Inhibition of AMPK, accomplished either through cell
      treatment or by adenovirus infection to express dominant-negative AMPK, was found
      to increase the level of HuR in the cytoplasm and to enhance the binding of HuR
      to p21, cyclin B1, and cyclin A mRNA transcripts and elevate their expression and
      half-lives. Conversely, AMPK activation, achieved by means including infection to
      express constitutively active AMPK, resulted in reduced cytoplasmic HuR;
      decreased levels and half-lives of mRNAs encoding p21, cyclin A, and cyclin B1;
      and diminished HuR association with the corresponding transcripts. We therefore
      propose a novel function for AMPK as a regulator of cytoplasmic HuR levels, which
      in turn influences the mRNA-stabilizing function of HuR and the expression of HuR
      target transcripts.

PMID- 11971976
TI  - Cell cycle arrest and apoptosis induced by human Polo-like kinase 3 is mediated
      through perturbation of microtubule integrity.
AB  - Human Polo-like kinase 3 (Plk3, previously termed Prk or Fnk) is involved in
      regulation of cell cycle progression through the M phase (B. Ouyang, H. Pan, L.
      Lu, J. Li, P. Stambrook, B. Li, and W. Dai, J. Biol. Chem. 272:28646-28651,
      1997). Here we report that in most interphase cells endogenous Plk3 was
      predominantly localized around the nuclear membrane. Double labeling with Plk3
      and gamma-tubulin, the latter a major component of pericentriole materials,
      revealed that Plk3 was closely associated with centrosomes and that its
      localization to centrosomes was dependent on the integrity of microtubules.
      Throughout mitosis, Plk3 appeared to be localized to mitotic apparatus such as
      spindle poles and mitotic spindles. During telophase, a significant amount of
      Plk3 was also detected in the midbody. Ectopic expression of Plk3 mutants
      dramatically changed cell morphology primarily due to their effects on
      microtubule dynamics. Expression of a constitutively active Plk3 (Plk3-A)
      resulted in rapid cell shrinkage, which led to formation of cells with an
      elongated, unsevered, and taxol-sensitive midbody. In contrast, cells expressing
      a kinase-defective Plk3 (Plk3(K52R)) mutant exhibited extended, deformed
      cytoplasmic structures, the phenotype of which was somewhat refractory to taxol
      treatment. Expression of both Plk3-A and Plk3(K52R) induced apparent G(2)/M
      arrest followed by apoptosis, although the kinase-defective mutant was less
      effective. Taken together, our studies strongly suggest that Plk3 plays an
      important role in the regulation of microtubule dynamics and centrosomal function
      in the cell and that deregulated expression of Plk3 results in cell cycle arrest
      and apoptosis.

PMID- 11971975
TI  - Alteration of large-scale chromatin structure by estrogen receptor.
AB  - The estrogen receptor (ER), a member of the nuclear hormone receptor superfamily
      important in human physiology and disease, recruits coactivators which modify
      local chromatin structure. Here we describe effects of ER on large-scale
      chromatin structure as visualized in live cells. We targeted ER to gene-amplified
      chromosome arms containing large numbers of lac operator sites either directly,
      through a lac repressor-ER fusion protein (lac rep-ER), or indirectly, by fusing
      lac repressor with the ER interaction domain of the coactivator steroid receptor
      coactivator 1. Significant decondensation of large-scale chromatin structure,
      comparable to that produced by the approximately 150-fold-stronger viral protein
      16 (VP16) transcriptional activator, was produced by ER in the absence of
      estradiol using both approaches. Addition of estradiol induced a partial reversal
      of this unfolding by green fluorescent protein-lac rep-ER but not by wild-type ER
      recruited by a lac repressor-SRC570-780 fusion protein. The chromatin
      decondensation activity did not require transcriptional activation by ER nor did
      it require ligand-induced coactivator interactions, and unfolding did not
      correlate with histone hyperacetylation. Ligand-induced coactivator interactions
      with helix 12 of ER were necessary for the partial refolding of chromatin in
      response to estradiol using the lac rep-ER tethering system. This work
      demonstrates that when tethered or recruited to DNA, ER possesses a novel large
      scale chromatin unfolding activity.

PMID- 11971977
TI  - Mutational analysis of all conserved basic amino acids in RAG-1 reveals
      catalytic, step arrest, and joining-deficient mutants in the V(D)J recombinase.
AB  - Although both RAG-1 and RAG-2 are required for all steps of V(D)J recombination,
      little is known about the specific contribution of either protein to these steps.
      RAG-1 contains three acidic active-site amino acids that are thought to
      coordinate catalytic metal ions. To search for additional catalytic amino acids
      and to better define the functional anatomy of RAG-1, we mutated all 86 conserved
      basic amino acids to alanine and evaluated the mutant proteins for DNA binding,
      nicking, hairpin formation, and joining. We found several amino acids outside of
      the canonical nonamer-binding domain that are critical for DNA binding, several
      step arrest mutants with defects in nicking or hairpin formation, and four RAG-1
      mutants defective specifically for joining. Analysis of coding joints formed by
      some of these mutants revealed excessive deletions, frequent use of short
      sequence homologies, and unusually long palindromic junctional inserts, known as
      P nucleotides, that result from aberrant hairpin opening. These features
      characterize junctions found in scid mice, which are deficient for the catalytic
      subunit of DNA-dependent protein kinase (DNA-PKcs), suggesting that the RAG
      proteins and DNA-PKcs perform overlapping functions in coding joint formation.
      Interestingly, the amino acids that are altered in 12 of our mutants are also
      mutated in human inherited immunodeficiency syndromes. Our analysis of these
      mutants provides insights into the molecular mechanisms underlying these
      disorders.

PMID- 11971979
TI  - Gene control in germinal differentiation: RNF6, a transcription regulatory
      protein in the mouse sertoli cell.
AB  - In mouse Sertoli cells, transcription of the Inha gene encoding the alpha subunit
      of inhibin, which acts locally as a tumor suppressor, is down-regulated in tumors
      and in normal cells during aging. Previous studies suggested that regulation of
      Inha transcription involves the binding of a protein(s) to a repeat of the GGGGC
      motif in the promoter. Expression screening identified a cDNA encoding a protein
      that binds this sequence. Of the RING-H2 family, it is the mouse homologue of a
      human protein of unknown function, RNF6. The mouse gene, Rnf6, is predominantly
      expressed in two interacting cell types of the testis, Sertoli cells and
      pachytene spermatocytes. In Sertoli cells, it colocalizes with the PML and Daxx
      proteins in punctate nuclear bodies. In transient and stable transfectants, Rnf6
      expression from a heterologous promoter increased the expression of reporter
      genes driven by the Inha promoter. In a Sertoli tumor cell line in which
      expression of both Inha and Rnf6 was reduced, reexpression of the latter restored
      the level of Inha while, concomitantly, the cells reverted to normal growth
      control in culture.

PMID- 11971978
TI  - Targeting assay to study the cis functions of human telomeric proteins: evidence
      for inhibition of telomerase by TRF1 and for activation of telomere degradation
      by TRF2.
AB  - We investigated the control of telomere length by the human telomeric proteins
      TRF1 and TRF2. To this end, we established telomerase-positive cell lines in
      which the targeting of these telomeric proteins to specific telomeres could be
      induced. We demonstrate that their targeting leads to telomere shortening. This
      indicates that these proteins act in cis to repress telomere elongation.
      Inhibition of telomerase activity by a modified oligonucleotide did not further
      increase the pace of telomere erosion caused by TRF1 targeting, suggesting that
      telomerase itself is the target of TRF1 regulation. In contrast, TRF2 targeting
      and telomerase inhibition have additive effects. The possibility that TRF2 can
      activate a telomeric degradation pathway was directly tested in human primary
      cells that do not express telomerase. In these cells, overexpression of full
      length TRF2 leads to an increased rate of telomere shortening.

PMID- 11971980
TI  - Oncogenic ras and p53 cooperate to induce cellular senescence.
AB  - Oncogenic activation of the mitogen-activated protein (MAP) kinase cascade in
      murine fibroblasts initiates a senescence-like cell cycle arrest that depends on
      the ARF/p53 tumor suppressor pathway. To investigate whether p53 is sufficient to
      induce senescence, we introduced a conditional murine p53 allele (p53(val135))
      into p53-null mouse embryonic fibroblasts and examined cell proliferation and
      senescence in cells expressing p53, oncogenic Ras, or both gene products.
      Conditional p53 activation efficiently induced a reversible cell cycle arrest but
      was unable to induce features of senescence. In contrast, coexpression of
      oncogenic ras or activated mek1 with p53 enhanced both p53 levels and activity
      relative to that observed for p53 alone and produced an irreversible cell cycle
      arrest that displayed features of cellular senescence. p19(ARF) was required for
      this effect, since p53(-/-) ARF(-/-) double-null cells were unable to undergo
      senescence following coexpression of oncogenic Ras and p53. Although the levels
      of exogenous p53 achieved in ARF-null cells were relatively low, the stabilizing
      effects of p19(ARF) on p53 could not explain the cooperation between oncogenic
      Ras and p53 in promoting senescence. Hence, enforced p53 expression without
      oncogenic ras in p53(-/-) mdm2(-/-) double-null cells produced extremely high p53
      levels but did not induce senescence. Taken together, our results indicate that
      oncogenic activation of the MAP kinase pathway in murine fibroblasts converts p53
      into a senescence inducer through both quantitative and qualitative mechanisms.

PMID- 11971981
TI  - Generation and characterization of Smac/DIABLO-deficient mice.
AB  - The mitochondrial proapoptotic protein Smac/DIABLO has recently been shown to
      potentiate apoptosis by counteracting the antiapoptotic function of the inhibitor
      of apoptosis proteins (IAPs). In response to apoptotic stimuli, Smac is released
      into the cytosol and promotes caspase activation by binding to IAPs, thereby
      blocking their function. These observations have suggested that Smac is a new
      regulator of apoptosis. To better understand the physiological function of Smac
      in normal cells, we generated Smac-deficient (Smac(-/-)) mice by using homologous
      recombination in embryonic stem (ES) cells. Smac(-/-) mice were viable, grew, and
      matured normally and did not show any histological abnormalities. Although the
      cleavage in vitro of procaspase-3 was inhibited in lysates of Smac(-/-) cells,
      all types of cultured Smac(-/-) cells tested responded normally to all apoptotic
      stimuli applied. There were also no detectable differences in Fas-mediated
      apoptosis in the liver in vivo. Our data strongly suggest the existence of a
      redundant molecule or molecules capable of compensating for a loss of Smac
      function.

PMID- 11971982
TI  - Fliih, a gelsolin-related cytoskeletal regulator essential for early mammalian
      embryonic development.
AB  - The Drosophila melanogaster flightless I gene is required for normal
      cellularization of the syncytial blastoderm. Highly conserved homologues of
      flightless I are present in Caenorhabditis elegans, mouse, and human. We have
      disrupted the mouse homologue Fliih by homologous recombination in embryonic stem
      cells. Heterozygous Fliih mutant mice develop normally, although the level of
      Fliih protein is reduced. Cultured homozygous Fliih mutant blastocysts hatch,
      attach, and form an outgrowing trophoblast cell layer, but egg cylinder formation
      fails and the embryos degenerate. Similarly, Fliih mutant embryos initiate
      implantation in vivo but then rapidly degenerate. We have constructed a
      transgenic mouse carrying the complete human FLII gene and shown that the FLII
      transgene is capable of rescuing the embryonic lethality of the homozygous
      targeted Fliih mutation. These results confirm the specific inactivation of the
      Fliih gene and establish that the human FLII gene and its gene product are
      functional in the mouse. The Fliih mouse mutant phenotype is much more severe
      than in the case of the related gelsolin family members gelsolin, villin, and
      CapG, where the homozygous mutant mice are viable and fertile but display
      alterations in cytoskeletal actin regulation.

PMID- 11971983
TI  - Tyrosine phosphorylation regulates alpha II spectrin cleavage by calpain.
AB  - Spectrins, components of the membrane skeleton, are implicated in various
      cellular functions. Understanding the diversity of these functions requires
      better characterization of the interacting domains of spectrins, such as the SH3
      domain. Yeast two-hybrid screening of a kidney cDNA library revealed that the SH3
      domain of alpha II-spectrin binds specifically isoform A of low-molecular-weight
      phosphotyrosine phosphatase (LMW-PTP). The alpha II-spectrin SH3 domain does not
      interact with LMW-PTP B or C nor does LMW-PTP A interact with the alpha I
      spectrin SH3 domain. The interaction of spectrin with LMW-PTP A led us to look
      for a tyrosine-phosphorylated residue in alpha II-spectrin. Western blotting
      showed that alpha II-spectrin is tyrosine phosphorylated in vivo. Using
      mutagenesis on recombinant peptides, we identified the residue Y1176 located in
      the calpain cleavage site of alpha II-spectrin, near the SH3 domain, as an in
      vitro substrate for Src kinase and LMW-PTP A. This Y1176 residue is also an in
      vivo target for kinases and phosphatases in COS cells. Phosphorylation of this
      residue decreases spectrin sensitivity to calpain in vitro. Similarly, the
      presence of phosphatase inhibitors in cell culture is associated with the absence
      of spectrin cleavage products. This suggests that the Y1176 phosphorylation state
      could modulate spectrin cleavage by calpain and may play an important role during
      membrane skeleton remodeling.

PMID- 11971984
TI  - The Schizosaccharomyces pombe rad60 gene is essential for repairing double-strand
      DNA breaks spontaneously occurring during replication and induced by DNA-damaging
      agents.
AB  - To identify novel genes involved in DNA double-strand break (DSB) repair, we
      previously isolated Schizosaccharomyces pombe mutants which are hypersensitive to
      methyl methanesulfonate (MMS) and synthetic lethals with rad2. This study
      characterizes one of these mutants, rad60-1. The gene that complements the MMS
      sensitivity of this mutant was cloned and designated rad60. rad60 encodes a
      protein with 406 amino acids which has the conserved ubiquitin-2 motif found in
      ubiquitin family proteins. rad60-1 is hypersensitive to UV and gamma rays,
      epistatic to rhp51, and defective in the repair of DSBs caused by gamma
      irradiation. The rad60-1 mutant is also temperature sensitive for growth. At the
      restrictive temperature (37 degrees C), rad60-1 cells grow for several divisions
      and then arrest with 2C DNA content; the arrested cells accumulate DSBs and have
      a diffuse and often aberrantly shaped nuclear chromosomal domain. The rad60-1
      mutant is a synthetic lethal with rad18-X, and expression of wild-type rad60 from
      a multicopy plasmid partially suppresses the MMS sensitivity of rad18-X cells.
      rad18 encodes a conserved protein of the structural maintenance of chromosomes
      (SMC) family (A. R. Lehmann, M. Walicka, D. J. Griffiths, J. M. Murray, F. Z.
      Watts, S. McCready, and A. M. Carr, Mol. Cell. Biol. 15:7067-7080, 1995). These
      results suggest that S. pombe Rad60 is required to repair DSBs, which accumulate
      during replication, by recombination between sister chromatids. Rad60 may perform
      this function in concert with the SMC protein Rad18.

PMID- 11971987
TI  - Evaluation of mutagenic effects of formaldehyde in vitro: detection of crosslinks
      and mutations in mouse lymphoma cells.
AB  - Formaldehyde (FA) is known to be a genotoxic substance. FA induces DNA-protein
      crosslinks (DPC) as the primary DNA lesion. However, the significance of DPC for
      FA-induced mutations and the mechanism(s) of mutation formation are at present
      poorly understood. Our previous results indicated that FA-induced DPC seem to be
      related to cytotoxicity and clastogenicity but do not lead to gene mutations in
      mammalian cells. We now demonstrate that FA efficiently induces mutations in the
      mouse lymphoma assay (MLA). Treatment of L5178Y cells with FA for 2 h caused a
      clear and concentration-related mutagenic effect in the MLA. As this mutagenic
      effect was mainly due to a strong increase in small colony mutants, we suggest
      that FA mainly causes mutations by induction of chromosomal aberrations.
      Molecular characterization of spontaneous and FA-induced mutants by loss of
      heterozygosity analysis showed an extensive loss of functional tk sequences,
      supporting a clastogenic mechanism of mutation formation. Whole chromosome
      fluorescence in situ hybridization was used to further elucidate the mechanism(s)
      of chromosome mutations. Our results indicate that small-scale chromosomal
      rearrangements (e.g. deletions or recombinations) are mainly involved in FA
      induced mutagenesis in the MLA.

PMID- 11971988
TI  - Measurement of cyclobutane thymidine dimers in melanocytic nevi and surrounding
      epidermis in human skin in situ.
AB  - The numbers of melanocytic nevi, localized benign proliferations of melanocytes,
      have been shown to be associated with an increased risk for development of
      melanoma. In the present study we have developed an alternative post-labelling
      method for determination of levels of cyclobutane thymidine dimers (T=T) as
      dinucleotides at sensitivities sufficient for analysis of human skin samples.
      Using the developed method, the induction of T=T was determined in melanocytic
      nevi in situ and surrounding skin, obtained from seven subjects, after exposure
      to solar simulating radiation. The T=T level in nevi was found to be 1- to 4.5
      fold lower than that in surrounding skin and the difference was statistically
      significant (Student's t-test, P < 0.05).

PMID- 11971985
TI  - Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I
      kappa B kinase.
AB  - In the past few years, many nuclear receptor coactivators have been identified
      and shown to be an integral part of receptor action. The most frequently studied
      of these coactivators are members of the steroid receptor coactivator (SRC)
      family, SRC-1, TIF2/GRIP1/SRC-2, and pCIP/ACTR/AIB-1/RAC-3/TRAM-1/SRC-3. In this
      report, we describe the biochemical purification of SRC-1 and SRC-3 protein
      complexes and the subsequent identification of their associated proteins by mass
      spectrometry. Surprisingly, we found association of SRC-3, but not SRC-1, with
      the I kappa B kinase (IKK). IKK is known to be responsible for the degradation of
      I kappa B and the subsequent activation of NF-kappa B. Since NF-kappa B plays a
      key role in host immunity and inflammatory responses, we therefore investigated
      the significance of the SRC-3-IKK complex. We demonstrated that SRC-3 was able to
      enhance NF-kappa B-mediated gene expression in concert with IKK. In addition, we
      showed that SRC-3 was phosphorylated by the IKK complex in vitro. Furthermore,
      elevated SRC-3 phosphorylation in vivo and translocation of SRC-3 from cytoplasm
      to nucleus in response to tumor necrosis factor alpha occurred in cells,
      suggesting control of subcellular localization of SRC-3 by phosphorylation.
      Finally, the hypothesis that SRC-3 is involved in NF-kappa B-mediated gene
      expression is further supported by the reduced expression of interferon
      regulatory factor 1, a well-known NF-kappa B target gene, in the spleens of SRC-3
      null mutant mice. Taken together, our results not only reveal the IKK-mediated
      phosphorylation of SRC-3 to be a regulated event that plays an important role but
      also substantiate the role of SRC-3 in multiple signaling pathways.

PMID- 11971989
TI  - Environmental factors affecting transcription of the human L1 retrotransposon. I.
      Steroid hormone-like agents.
AB  - The L1 retrotransposon has significantly shaped the structure of the human
      genome. At least 30% of human genome sequence can be attributed to L1 reverse
      transcriptase activity. There are 10(5) copies of the human L1 retrotransposon,
      L1Hs, most of which are defective, although approximately 8-9 x 10(3) are full
      length. L1Hs elements transpose through an RNA intermediate and transcription is
      thought to be the rate limiting step in retrotransposition. Because transcription
      of retrotransposons in a variety of organisms has been shown to respond to
      environmental stimuli, we investigated the influence of various agents on
      transcription from two different L1Hs promoters. The activity of the L1Hs
      promoters was analyzed by transfecting L1Hs-expressing cell lines with plasmids
      containing the L1Hs promoters fused to the LacZ reporter gene and monitoring
      expression with a beta-galactosidase assay. Small increases in beta-galactosidase
      activity were observed with both L1Hs promoters after treatment with serum,
      testosterone, dihydrotestosterone and organochloride pesticides, indicating that
      these agents can influence L1Hs transcription.

PMID- 11971991
TI  - Cryopreserved versus freshly isolated lymphocytes in human biomonitoring:
      endogenous and induced DNA damage, antioxidant status and repair capability.
AB  - Lymphocytes are routinely used in human biomonitoring to assess the potential
      toxic and cytoprotective effects of diet on both DNA damage and repair and, by
      implication, health. Logistically, samples may require to be cryopreserved and
      stored. How this affects cells used in human biomonitoring is often not
      considered. In this study we have evaluated the influence of cryopreservation on
      endogenous and induced DNA strand breakage, altered bases (oxidized purines,
      oxidized pyrimidines and misincorporated uracil), antioxidant capacity and DNA
      repair capability in human peripheral blood lymphocytes. Neither isolation nor
      freezing increased DNA strand breakage above endogenous levels found in freshly
      isolated human lymphocytes. Oxidized bases (both pyrimidines and purines) and
      misincorporated uracil, were similar for fresh and frozen lymphocytes. Fresh and
      frozen lymphocytes responded almost identically to hydrogen peroxide. Quercetin
      mediated cytoprotection against hydrogen peroxide-induced strand breakage was
      maintained in cryopreserved lymphocytes after short-term (24 h) and longer term
      (2 months) storage compared with freshly isolated and treated cells. Hydrogen
      peroxide-induced DNA strand breakage was repaired in fresh lymphocytes.
      Cryopreserved lymphocytes were unable to repair oxidant-induced DNA strand
      breaks. Frozen human lymphocytes can therefore be successfully used for most
      aspects of DNA damage biomonitoring, but not for repair.

PMID- 11971990
TI  - Assessment of the genotoxic potential of ISIS 2302: a phosphorothioate
      oligodeoxynucleotide.
AB  - ISIS 2302, a phosphorothioate oligodeoxynucleotide with antisense activity
      against human ICAM-1 mRNA, was evaluated in a battery of tests to assess
      genotoxic potential. There was no evidence of genotoxicity in three in vitro
      studies performed: (i) a bacterial reverse mutation test; (ii) a chromosomal
      aberration test in Chinese hamster ovary cells; (iii) a mammalian cell gene
      mutation assay in L5187Y cells. Additionally, there was no in vivo evidence of
      genetic toxicity in a bone marrow micronucleus study in male and female mice. For
      all tests, top concentrations or doses assessed met harmonized regulatory
      guidelines. The cellular uptake of ISIS 2302 into target cells was confirmed
      using capillary gel electrophoresis and immunohistochemistry. Intracellular
      uptake into CHO cells, L5187Y cells, Salmonella typhimurium TA98 and bone marrow
      was concentration- and time-dependent. Consistent with what is known about the
      physical and chemical properties of phosphorothioate oligodeoxynucleotides, there
      was no evidence of genotoxicity in any of the assessed end-points. Furthermore,
      the absence of genotoxicity could not be ascribed to test system insensitivity or
      to an absence of exposure of the test system to ISIS 2302.

PMID- 11971992
TI  - Induction effects of sulfur dioxide inhalation on chromosomal aberrations in
      mouse bone marrow cells.
AB  - To investigate the induction of chromosome aberrations (CA) in mouse bone marrow
      cells by sulfur dioxide (SO(2)) inhalation, mice were treated by SO(2) exposure
      for 4 h/day for 7 days at various concentrations of SO(2), then mitotic indices
      and CA in mouse bone marrow cells were analyzed. The present results show that
      SO(2) might increase the frequencies of CA and aberrant cells in mouse bone
      marrow in a dose-dependent manner. The frequencies (%) of aberrant cells in mouse
      bone marrow induced by SO(2) at concentrations of 0, 7, 14, 28 and 56 mg/m(3)
      were 1.81, 3.00, 3.58, 4.26, 4.86, respectively. At low concentrations SO(2)
      induced only chromatid-type CA, while at high concentrations SO(2) induced both
      chromatid-type and chromosome-type CA. SO(2) inhalation decreased the mitotic
      indices of bone marrow cells. The results imply that SO(2) inhalation may inhibit
      mitoses and increase CA frequencies of bone marrow cells and that it is a
      clastogenetic and genotoxic agent. Long exposure to SO(2) pollution at low
      concentrations in the environment may be a potential risk for induction of
      cytogenetic damage in vivo in humans.

PMID- 11971993
TI  - Griseofulvin induces mitotic delay and aneuploidy in bone marrow cells of orally
      treated mice.
AB  - Griseofulvin (GF) is a fungicide drug well characterized for its aneugenic
      activity in vitro. In vivo strong evidence of aneuploidy and polyploidy induction
      has been obtained in germ cells, especially in oocytes. More controversial are
      the data on the aneugenicity of griseofulvin in somatic cells. In this paper we
      provide evidence that GF induces non-disjunction and cell cycle delay in bone
      marrow cells of orally treated mice. Adult female mice were administered olive
      oil suspensions of 200, 666 or 2000 mg/kg GF by gavage and killed 18 or 24 h
      later. To minimize animal-to-animal variation in the absorption and distribution
      of GF, mice were fasted from the time of GF administration to the time of
      killing. Two hours before treatment the animals were s.c. implanted with a
      bromodeoxyuridine tablet to obtain differential chromatid staining and to
      determine the number of divisions after GF treatment for each metaphase.
      Mitostatic effects of GF were assessed by the relative proportions of first,
      second and third generation metaphases and the average generation time (AGT)
      method. A statistically significant increase with respect to the control AGT
      value was observed after treatment with 666 and 2000 mg/kg, suggesting that GF,
      as already shown in meiosis, interfered with cell cycle progression. Hyperploidy
      was scored in second generation metaphases. Eighteen hours after treatment, the
      frequencies of hyperploid cells were significantly (P < 0.05) higher in all GF
      treated groups than in their matched control group. The effect was not dose
      dependent. No further increase in aneuploidy was observed at 24 h, suggesting
      that cells overcoming mitotic arrest did not have a higher rate of non
      disjunction. No induction of polyploidy was demonstrated. We conclude that GF
      induces mitotic delay and aneuploidy in mouse bone marrow and suggest that the
      protocol used to formulate the gavage suspensions and the after-treatment fasting
      of the animals enhanced the bioavailability of GF to bone marrow cells.

PMID- 11971994
TI  - Assessment of genotoxic effects related to chronic low level exposure to ionizing
      radiation using biomarkers for DNA damage and repair.
AB  - The first objective of our study was to analyse whether biomarkers for genotoxic
      effects (DNA breaks and alkali-labile sites and micronucleus and non-disjunction
      frequencies) could be fully validated for biomonitoring workers chronically
      exposed to ionizing radiation (IR). Blood samples of controls and individuals
      chronically exposed to IR were analysed. The interindividual variation was
      reduced when the comet data were adjusted for interexperimental variation, but
      remained statistically significant. No differences were found between groups,
      either for smoking or for exposure status. The second objective was to determine
      whether the Comet assay can be used to evaluate global repair phenotype as a
      susceptibility biomarker for IR-induced DNA damage in nuclear workers. A pilot
      study was performed and blood from workers exposed or not to radiation was
      submitted to a challenging dose of gamma-rays. The repair kinetics of each
      individual donor were analysed by Comet assay at different time points and
      compared with the frequencies of biomarkers of genotoxic effects. There was a
      statistically significant interaction between biomarkers assessing the same
      damage (micronucleus and Comet assays). Multivariate analysis showed that
      micronucleus frequencies were positively influenced by age and the percentage of
      residual tail length was negatively influenced by the interaction between smoking
      and exposure status. The general conclusions from our study are: (i) a positive
      correlation exists between mechanistically related biomarkers; (ii) multivariate
      regression analysis confirmed that the interaction between smoking and exposure
      to IR negatively and statistically significantly influenced residual tail length;
      (iii) use of the Comet assay for the estimation of global repair phenotype with
      respect to IR is recommended because it is simple, fast and differences in in
      vitro repair capacity can be detected.

PMID- 11971995
TI  - Spontaneous and spindle poison-induced micronuclei and chromosome non-disjunction
      in cytokinesis-blocked lymphocytes from two age groups of women.
AB  - Fluorescence in situ hybridization (FISH) was used to evaluate spontaneous and
      aneuploidogen-induced micronucleus frequencies and non-disjunction of chromosomes
      X and 8 in cultured binucleated lymphocytes of women of two age groups.
      Demecolcine and vincristine were used as model aneuploidogens to induce
      micronuclei and chromosome malsegregation. Four of the women were aged 22-26
      (mean 24.3) years and four 47-50 (mean 49.0) years. Pancentromeric FISH was
      applied to micronuclei to identify chromosomes and double-color centromeric FISH,
      performed in binucleates of two young and two older women, was used to assess the
      involvement of chromosomes X and 8 in micronuclei and non-disjunction. It was
      confirmed that age increases micronucleus frequency. Micronuclei containing whole
      chromosomes predominated in older females. Age also enhanced micronuclei
      containing acentric chromosome fragments. The inclusion of chromosomes X and 8 in
      micronuclei was enhanced by age and chromosome X was generally overrepresented.
      Non-disjunction of chromosomes X and 8 also increased with age, chromosome X
      being the more sensitive. Treatment of lymphocytes with vincristine and
      demecolcine increased micronucleus frequency and malsegregation of chromosomes X
      and 8 in both age groups. Comparison of the estimated frequencies of
      micronucleation and non-disjunction for all human chromosomes showed that non
      disjunction is the main type of chromosome malsegregation.

PMID- 11971997
TI  - Effect of ethanol treatment on metabolic activation and detoxification of
      esophagus carcinogenic N-nitrosamines in rat liver.
AB  - In order to elucidate the mechanism underlying enhancement by ethanol of N
      nitrosodiethylamine (DEN)- and N-nitrosomethylbenzylamine (NMBA)-induced
      esophageal tumorigenesis in rats, hepatic levels of cytochrome P-450 (CYP)
      enzymes, mutagenic activation of several N-nitrosamines and three kinds of UDP
      glucuronyltransferase (UDPGT) activities were assayed in F344 rats. Immunoblot
      analyses of microsomal CYP proteins revealed induction of CYP2E1 (approximately 2
      fold), but not CYP2B1/2, 1A1/2 or 3A2, by treatment with 10% ethanol in the
      drinking water for 2 weeks. In contrast, s.c. treatment with 0.5 mg/kg NMBA three
      times per week for 2 weeks produced no significant alterations in the levels of
      these CYP species. Ethanol treatment also elevated the mutagenic activities of N
      nitrosodimethylamine (DMN), DEN and N-nitrosopyrrolidine (NPYR) in strain TA100
      up to 2.1-, 1.6- and 2.3-fold above each control, respectively. However, this was
      not the cases for four N-nitrosamines, including NMBA, in strain TA100 and two
      heterocyclic amines and aflatoxin B(1) in strain TA98. In addition, ethanol did
      not affect UDPGT activities towards 4-nitrophenol, bilirubin and testosterone.
      Hepatic CYP species responsible for mutagenic activation of selected N
      nitrosodialkylamines were confirmed by use of specific CYP inducers and
      inhibitors with the liver from F344 and Wistar rats, indicating that DMN, DEN and
      NMBA are selectively activated by CYP2E1, predominantly by CYP2E1 with a slight
      contribution by CYP2B2 and selectively by CYP2B1/2, respectively. These results
      demonstrate that ethanol exerts an enhancing effect on mutagenic activation by
      CYP2E1 of DMN, DEN and NPYR, but does not affect that of NMBA and the other
      carcinogens by CYP2B1/2, 1A1/2 and 3A2 and UDPGT1A1, 1A6 and 2B1 activities.
      Consequently, this suggests that enhancement by ethanol of DEN-induced esophageal
      carcinogenesis in F344 rats can be attributed to an increase in hepatic
      activation during the initiation phase, but that of NMBA-induced tumorigenesis is
      not attributable to metabolic activation and inactivation via glucuronidation in
      liver.

PMID- 11971996
TI  - Impairment of cell cycle progression by aflatoxin B1 in human cell lines.
AB  - Aflatoxin B1 is a mycotoxin produced by Aspergillus flavus and Aspergillus
      parasiticum, which may be present as a food contaminant. It is known to cause
      acute toxic effects and act as a carcinogenic agent. The carcinogenic action has
      been related to its ability to form unstable adducts with DNA, which represent
      possible mutagenic sites. On the other hand, the primary cellular target
      responsible for its toxic action has not yet been clearly identified. Previous
      data suggested a possible correlation between cell proliferation and
      responsiveness to aflatoxin toxicity. These observations led us to investigate
      the effect of the toxin on cell cycle progression of three human cell lines
      (HepG2, SK-N-MC and SK-N-SH derived from liver and nervous tissue tumours); they
      were shown to display different responses to toxin exposure and have different
      growth kinetics. We performed analysis of the cell cycle, DNA synthesis and
      expression of p21 and p53 in the presence and absence of the toxin in all cell
      lines exposed. The results of cell cycle cytofluorometric analysis show
      significant alterations of cell cycle progression as a result of toxin treatment.
      In all cell lines exposure to a 24 h toxin treatment causes a dose-dependent
      accumulation in S phase, however, the ability to recover from impairment to
      traverse S phase varies in the cell lines under study. SK-N-MC cells appear more
      prone to resume DNA synthesis when the toxin is removed, while the other two cell
      lines maintain a significant inhibition of DNA synthesis, as indicated by
      cytofluorimetry and [(3)H]dTR incorporation. The level of p53 and p21 expression
      in the three cell lines was examined by western blot analysis and significant
      differences were detected. The ready resumption of DNA synthesis displayed by SK
      N-MC cells could possibly be related to the absence of p53 control of cell cycle
      progression.

PMID- 11971998
TI  - Fumonisin B(1) is genotoxic in human derived hepatoma (HepG2) cells.
AB  - Fumonisin B(1) (FB(1)), a widespread Fusarium toxin which is frequently found in
      corn, causes liver tumors in laboratory rodents and is a suspected human
      carcinogen. The compound was tested in micronucleus (MN) and single cell gel
      electrophoresis (SCGE) assays in human derived hepatoma (HepG2) cells and caused
      a pronounced dose-dependent genotoxic effect at exposure concentrations > or = 25
      microg/ml. In contrast, no induction of his(+) revertants was found in Salmonella
      microsome assays with strains TA98, TA100, TA102, TA1535 and TA1537 upon addition
      of HepG2-derived enzyme (S9) mix in liquid incubation assays with identical
      exposure concentrations. Taken together, our results indicate that FB(1) is
      clastogenic in human derived cells. This observation supports the assumption that
      this compound may act as a genotoxic carcinogen in humans.

PMID- 11971999
TI  - Low molecular weight polyethylene glycol induces chromosome aberrations in
      Chinese hamster cells cultured in vitro.
AB  - The human population is widely exposed to polyethylene glycol (PEG) and its
      chemical derivatives, which are widely used as vehicles or co-solvents in many
      pharmaceutical and cosmetic preparations. However, PEG polymers of low molecular
      weight differ significantly from polymers of higher molecular weight in their
      physico-chemical properties, biological effects on cell permeability and their
      absorption and excretion, as well as their higher toxicity and possibly
      genotoxicity. In the present study we have analysed the induction of chromosome
      aberrations by the low molecular weight PEG polymers tetraethylene glycol (TEG),
      PEG 200 and PEG 400 in a Chinese hamster epithelial liver (CHEL) cell line, which
      retains sufficient metabolic capability to activate different promutagens and
      procarcinogens. The results indicate that in CHEL cells only TEG and PEG 200 are
      clastogenic. Parallel experiments performed in CHO cells in the presence and
      absence of rat liver S9 mix showed significant increases in chromosomal
      aberrations only in cultures treated with TEG in the presence of rat liver S9,
      indicating that low molecular weight polymers need to be activated to exert their
      genotoxic activity.

PMID- 11972000
TI  - Physical chemistry of nucleic acids.
AB  - The Watson-Crick double helix of DNA was first revealed in 1953. Since then a
      wide range of physical chemical methods have been applied to DNA and to its more
      versatile relative RNA to determine their structures and functions. My major goal
      is to predict the folded structure of any RNA from its sequence. We have used
      bulk and single-molecule measurements of thermodynamics and kinetics, plus
      various spectroscopic methods (UV absorption, optical rotation, circular
      dichroism, circular intensity differential scattering, fluorescence, NMR) to
      approach this goal.

PMID- 11972001
TI  - Higher-order optical correlation spectroscopy in liquids.
AB  - Linear optical spectroscopies have long been used to study the behavior of
      liquids. Laser technology has progressed to the point that it has become possible
      to perform nonlinear optical experiments that probe higher-order correlation
      functions in liquids, opening a new window into our understanding of the
      microscopic details of solution-phase processes. Here we review advances that
      have been made in recent years in employing higher-order electronic and
      vibrational spectroscopies to study liquid-state dynamics and structure.

PMID- 11972002
TI  - Time-resolved photoelectron angular distributions: concepts, applications, and
      directions.
AB  - The use of photoelectron angular distributions (PADs) as a probe in short-pulse,
      pump-probe scenarios is reviewed. We focus on concepts, on the insight that can
      be gained through theoretical analysis, on applications, and on future
      opportunities. Time-resolved PADs are sensitive to both the time-evolving
      rotational composition of wavepackets and their time-evolving electronic
      symmetry. The former feature renders this observable a potential probe of
      molecular structure, intensity effects, and rotational perturbations. The latter
      feature renders the PAD a potential probe of radiationless transitions.

PMID- 11972003
TI  - Scattering resonances in the simplest chemical reaction.
AB  - Recent studies of state-resolved angular distributions show the participation of
      reactive scattering resonances in the simplest chemical reaction. This review is
      intended for those who wish to learn about the state-of-the-art in the study of
      the H + H2 reaction family that has made this breakthrough possible. This review
      is also intended for those who wish to gain insight into the nature of reactive
      scattering resonances. Following a tour across several fields of physics and
      chemistry where the concept of resonance has been crucial for the understanding
      of new phenomena, we offer an operational definition and taxonomy of reactive
      scattering resonances. We introduce simple intuitive models to illustrate each
      resonance type. We focus next on the last decade of H + H2 reaction dynamics.
      Emphasis is placed on the various experimental approaches that have been applied
      to the search for resonance behavior in the H + H2 reaction family. We conclude
      by sketching the road ahead in the study of H + H2 reactive scattering
      resonances.

PMID- 11972004
TI  - Vacuum ultraviolet spectroscopy and chemistry by photoionization and
      photoelectron methods.
AB  - The recent developments of vacuum ultraviolet (VUV) laser and third generation
      synchrotron radiation sources, together with the introduction of pulsed field
      ionization (PFI) schemes for photoion-photoelectron detection, have had a
      profound impact on the field of VUV spectroscopy and chemistry. Owing to the
      mediation of near-resonant autoionizing states, rovibronic states of ions with
      negligible Franck-Condon factors for direct photoionization can be examined by
      VUV-PFI measurements with rotational resolutions. The VUV-PFI spectra thus
      obtained have provided definitive ionization energies (IEs) for many small
      molecules. The recent synchrotron-based PFI-photoelectron-photoion coincidence
      experiments have demonstrated that dissociative photoionization thresholds for a
      range of molecules can be determined to the same precision as in PFI
      photoelectron measurements. Combining appropriate dissociation thresholds and IEs
      measured in PFI studies, thermochemical data for many neutrals and cations can be
      determined with unprecedented precision. The further development of two-color
      excitation-ionization schemes promises to expand the scope of spectroscopic and
      chemical applications using the photoionization-photoelectron method.

PMID- 11972005
TI  - The molecular Hamiltonian.
AB  - The molecular Hamiltonian represents one of the most basic concepts in
      spectroscopy and molecular reaction dynamics. Its derivation is notoriously
      difficult owing to the use of a rotating reference frame which, in turn, is
      necessary to define the concept of vibration and rotation. In this article, we
      review the construction of the molecular Hamiltonian in normal mode and in
      internal coordinates. For normal mode coordinates, the Watson Hamiltonian
      including its modification for linear molecules is derived using an approach
      based on classical mechanics and the Podolsky transformation. The method is
      subsequently used to derive the molecular Hamiltonian in terms of Jacobi and
      valence coordinates. Results are presented for the triatomic system and for the
      extension toward N-atom systems with N > or = 3.

PMID- 11972006
TI  - Reversible polymerizations and aggregations.
AB  - The aggregation of monomers into polymers, whether by covalent or noncovalent
      interactions, is often reversible and frequently occurs with the entropy and
      enthalpy of the aggregation sharing the same sign. In such a case, the
      aggregation goes forward or reverses, depending on such variables as temperature
      and composition, rather like a phase transition. We explore the physical
      chemistry of three such systems: an organic monomer (alpha-methylstyrene), an
      inorganic monomer (sulfur), and a biopolymer (actin). We compare the available
      theories and experiments and list issues still open.

PMID- 11972007
TI  - Scanning tunneling microscopy studies of the one-dimensional electronic
      properties of single-walled carbon nanotubes.
AB  - Recent developments in scanning tunneling microscopy studies of the electronic
      properties of single-walled carbon nanotubes are reviewed. A broad range of
      topics focused on the unique electronic properties of nanotubes are discussed,
      including (a) the underlying theoretical description of the electronic properties
      of nanotubes; (b) the roles of finite curvature and broken symmetries in
      perturbing electronic properties; (c) the unique one-dimensional energy
      dispersion in nanotubes; (d) the nature of end states; (e) quantum size effects
      in short tubes; (f) the interactions between local spins and carriers in metallic
      systems (the Kondo effect); and (g) the atomic structure and electronic
      properties of intramolecular junctions. The implications of these studies for
      understanding fundamental one-dimensional physics and future nanotube device
      applications are discussed.

PMID- 11972008
TI  - Electron transfer at molecule-metal interfzces: a two-photon photoemission study.
AB  - Electron transfer between a molecular resonance and a metal surface is a
      ubiquitous process in many chemical disciplines, ranging from molecular
      electronics to surface photochemistry. This problem has been probed recently by
      two-photon photoemission spectroscopy. The first photon excites an electron from
      an occupied metal state to an unoccupied molecular resonance. Subsequent
      evolution of the excited electronic wavefunction is probed in energy, momentum,
      and time domains by the absorption of a second photon, which ionizes the electron
      for detection. These experiments reveal the important roles of molecule-metal
      wavefunction mixing, intermolecular band formation, polarization, and
      localization in interfacial electron transfer.

PMID- 11972009
TI  - Ab initio molecular dynamics with density functional theory.
AB  - Recent applications of density functional theory base ab initio molecular
      dynamics in chemical relevant systems are reviewed. The emphasis is on the
      dynamical aspect in the study of structures, reaction mechanisms, and electronic
      properties in both the molecular and condensed phases. Examples were chosen from
      fluxional molecules, solution reactions, and biological systems to illustrate the
      broad potential applications and unique information that can be obtained from ab
      initio molecular dynamics calculations. Recent advances in the development of
      efficient numerical algorithms for the prediction of spectroscopic properties are
      highlighted.

PMID- 11972010
TI  - Transition path sampling: throwing ropes over rough mountain passes, in the dark.
AB  - This article reviews the concepts and methods of transition path sampling. These
      methods allow computational studies of rare events without requiring prior
      knowledge of mechanisms, reaction coordinates, and transition states. Based upon
      a statistical mechanics of trajectory space, they provide a perspective with
      which time dependent phenomena, even for systems driven far from equilibrium, can
      be examined with the same types of importance sampling tools that in the past
      have been applied so successfully to static equilibrium properties.

PMID- 11972011
TI  - Electronic structure and catalysis on metal surfaces.
AB  - The powerful computational resources available to scientists today, together with
      recent improvements in electronic structure calculation algorithms, are providing
      important new tools for researchers in the fields of surface science and
      catalysis. In this review, we discuss first principles calculations that are now
      capable of providing qualitative and, in many cases, quantitative insights into
      surface chemistry. The calculations can aid in the establishment of chemisorption
      trends across the transition metals, in the characterization of reaction pathways
      on individual metals, and in the design of novel catalysts. First principles
      studies provide an excellent fundamental complement to experimental
      investigations of the above phenomena and can often allow the elucidation of
      important mechanistic details that would be difficult, if not impossible, to
      determine from experiments alone.

PMID- 11972012
TI  - Chemical shifts in amino acids, peptides, and proteins: from quantum chemistry to
      drug design.
AB  - This chapter discusses recent progress in the investigation and use of (13)C,
      (15)N, and (19)F nuclear magnetic resonance (NMR) chemical shifts and chemical
      shift tensors in proteins and model systems primarily using quantum chemical (ab
      initio Hartree-Fock and density functional theory) techniques. Correlations
      between spectra and structure are made and the techniques applied to other
      spectroscopic and electrostatic properties as well, including hydrogen bonding,
      ligand binding to heme proteins, J-couplings, electric field gradients, and atoms
      in-molecules theory, together with a brief review of the use of NMR chemical
      shifts in drug design.

PMID- 11972013
TI  - Reactive collisions of hyperthermal energy molecular ions with solid surfaces.
AB  - Recent experimental advances have uncovered many of the diverse reaction pathways
      following an energetic collision between a molecular ion and a solid surface.
      Hyperthermal translational energies (5-500 eV) are sufficient to activate a
      number of chemical transformations in the near-surface region, including charge
      transfer, dissociation, abstraction, and deposition. State-of-the-art scattering
      studies probe the consumption and disposal of energy and the effects of approach
      geometry and surface electronic structure on the operative reaction mechanisms.
      These fundamental investigations provide insight relevant to the fabrication of
      microelectronics devices, the interaction of space vehicles with the earth's
      atmosphere, and the development of analytical techniques in mass spectrometry.

PMID- 11972014
TI  - Molecular theory of hydrophobic effects: "She is too mean to have her name
      repeated.".
AB  - This paper reviews the molecular theory of hydrophobic effects relevant to
      biomolecular structure and assembly in aqueous solution. Recent progress has
      resulted in simple, validated molecular statistical thermodynamic theories and
      clarification of confusing theories of decades ago. Current work is resolving
      effects of wider variations of thermodynamic state, e.g., pressure denaturation
      of soluble proteins, and more exotic questions such as effects of surface
      chemistry in treating stability of macromolecular structures in aqueous solution.

PMID- 11972015
TI  - Studies of polymer surfaces by sum frequency generation vibrational spectroscopy.
AB  - Recently, sum frequency generation (SFG) vibrational spectroscopy has been
      developed into a powerful technique to study surfaces of polymer materials. This
      review summarizes the significant achievements in understanding surface molecular
      chemical structures of polymer materials obtained by SFG. It reviews in situ
      detection at the molecular level of surface structures of some common polymers in
      air, surface segregation of small end groups, polymer surface restructuring in
      water, and step-wise changed polymer blend surfaces. Studies of surface glass
      transition and surface structures modified by rubbing, plasma deposition, UV
      light irradiation, oxygen ion and radical irradiation, and wet etching are also
      discussed. SFG probing of polymer surfaces provides valuable insights into the
      relations between polymer surface structures and surface properties, which will
      assist in the design of polymer materials with desired surface properties.

PMID- 11972017
TI  - Surface femtochemistry: observation and quantum control of frustrated desorption
      of alkali atoms from noble metals.
AB  - This review presents a case study of the direct, real-time observation of a
      surface photochemical reaction, namely the frustrated photodesorption of alkali
      atoms from noble metal surfaces. Charge transfer excitation of an electron from
      the metal substrate into an unoccupied resonance of the alkali atom
      instantaneously turns on the repulsive Coulomb force inducing the nuclear motion
      of both the adsorbate and substrate atoms. The incipient nuclear wave packet
      dynamics are documented for the case of Cs/Cu(111) through the accompanying
      change in the surface electronic structure. The intimate view of atoms attempting
      to escape the surface bond highlights the unique role of the substrate in the
      electronic and nuclear dynamics that ultimately determine the product yields.
      Moreover, slow dephasing of the coherent polarization is exploited to demonstrate
      the control of nuclear wave packets through the phase of the excitation light.

PMID- 11972016
TI  - Quantum mechanical methods for enzyme kinetics.
AB  - This review discusses methods for the incorporation of quantum mechanical effects
      into enzyme kinetics simulations in which the enzyme is an explicit part of the
      model. We emphasize three aspects: (a) use of quantum mechanical electronic
      structure methods such as molecular orbital theory and density functional theory,
      usually in conjunction with molecular mechanics; (b) treating vibrational motions
      quantum mechanically, either in an instantaneous harmonic approximation, or by
      path integrals, or by a three-dimensional wave function coupled to classical
      nuclear motion; (c) incorporation of multidimensional tunneling approximations
      into reaction rate calculations.

PMID- 11972018
TI  - Connecting local structure to interface formation: a molecular scale van der
      Waals theory of nonuniform liquids.
AB  - This article reviews a new and general theory of nonuniform fluids that naturally
      incorporates molecular scale information into the classical van der Waals theory
      of slowly varying interfaces. The method optimally combines two standard
      approximations, molecular (mean) field theory to describe interface formation and
      linear response (or Gaussian fluctuation) theory to describe local structure.
      Accurate results have been found in many different applications in nonuniform
      simple fluids and these ideas may have important implications for the theory of
      hydrophobic interactions in water.

PMID- 11972019
TI  - Curvature of co-links uncovers hidden thematic layers in the World Wide Web.
AB  - Beyond the information stored in pages of the World Wide Web, novel types of
      "meta-information" are created when pages connect to each other. Such meta
      information is a collective effect of independent agents writing and linking
      pages, hidden from the casual user. Accessing it and understanding the
      interrelation between connectivity and content in the World Wide Web is a
      challenging problem [Botafogo, R. A. & Shneiderman, B. (1991) in Proceedings of
      Hypertext (Assoc. Comput. Mach., New York), pp. 63-77 and Albert, R. & Barabasi,
      A.-L. (2002) Rev. Mod. Phys. 74, 47-97]. We demonstrate here how thematic
      relationships can be located precisely by looking only at the graph of
      hyperlinks, gleaning content and context from the Web without having to read what
      is in the pages. We begin by noting that reciprocal links (co-links) between
      pages signal a mutual recognition of authors and then focus on triangles
      containing such links, because triangles indicate a transitive relation. The
      importance of triangles is quantified by the clustering coefficient [Watts, D. J.
      & Strogatz, S. H. (1999) Nature (London) 393, 440-442], which we interpret as a
      curvature [Bridson, M. R. & Haefliger, A. (1999) Metric Spaces of Non-Positive
      Curvature (Springer, Berlin)]. This curvature defines a World Wide Web landscape
      whose connected regions of high curvature characterize a common topic. We show
      experimentally that reciprocity and curvature, when combined, accurately capture
      this meta-information for a wide variety of topics. As an example of future
      directions we analyze the neural network of Caenorhabditis elegans, using the
      same methods.

PMID- 11972020
TI  - Climate change hastens population extinctions.
AB  - Climate change is expected to alter the distribution and abundance of many
      species. Predictions of climate-induced population extinctions are supported by
      geographic range shifts that correspond to climatic warming, but few extinctions
      have been linked mechanistically to climate change. Here we show that extinctions
      of two populations of a checkerspot butterfly were hastened by increasing
      variability in precipitation, a phenomenon predicted by global climate models. We
      model checkerspot populations to show that changes in precipitation amplified
      population fluctuations, leading to rapid extinctions. As populations of
      checkerspots and other species become further isolated by habitat loss, climate
      change is likely to cause more extinctions, threatening both species diversity
      and critical ecosystem services.

PMID- 11972021
TI  - Utility and distribution of conserved noncoding sequences in the grasses.
AB  - Control of gene expression requires cis-acting regulatory DNA sequences.
      Historically these sequences have been difficult to identify. Conserved noncoding
      sequences (CNSs) have recently been identified in mammalian genes through cross
      species genomic DNA comparisons, and some have been shown to be regulatory
      sequences. Using sequence alignment algorithms, we compared genomic noncoding DNA
      sequences of the liguleless1 (lg1) genes in two grasses, maize and rice, and
      found several CNSs in lg1. These CNSs are present in multiple grass species that
      represent phylogenetically disparate lineages. Six other maize/rice genes were
      compared and five contained CNSs. Based on nucleotide substitution rates, these
      CNSs exist because they have biological functions. Our analysis suggests that
      grass CNSs are smaller and far less frequent than those identified in mammalian
      genes and that mammalian gene regulation may be more complex than that of
      grasses. CNSs make excellent pan-grass PCR-based genetic mapping tools. They
      should be useful as characters in phylogenetic studies and as monitors of gene
      regulatory complexity.

PMID- 11972022
TI  - General and variable features of varicosity spacing along unmyelinated axons in
      the hippocampus and cerebellum.
AB  - Along unmyelinated central axons, synapses occur at focal swellings called axonal
      varicosities (boutons). The mechanisms regulating how frequently synapses and
      varicosities occur along axons remain poorly understood. Here, to investigate
      varicosity distribution patterns and the extent to which they may be conserved
      across different axons, we analyzed varicosity numbers and positions along
      fluorescently labeled axon branches in hippocampal area CA1 (CA3-to-CA1 "Schaffer
      collateral" axons) and five other synaptic regions of rat hippocampus and
      cerebellum. Varicosity spacing varied by region; e.g., 3.7 +/- 0.6 microm (mean
      +/- SD) for CA3-to-CA1 axons and 5.2 +/- 1.0 microm for cerebellar parallel
      fibers. Surprisingly, when 56 axons from these different regions were pooled into
      a single heterogeneous group, a general relationship emerged: the spacing
      variability (SD) was a constant fraction of the mean spacing, suggesting that
      varicosities along different axons are distributed in a fundamentally similar,
      scaled manner. Varicosity spacing was neither regular nor random but followed a
      pattern consistent with random synaptic distributions and the occurrence of
      multiple-synapse boutons. A quantitative model reproduced the salient features of
      the data and distinguished between two proposed mechanisms relating axonal
      morphogenesis and synaptogenesis.

PMID- 11972023
TI  - Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to
      IFN-gamma.
AB  - In response to IFN-gamma, the latent cytoplasmic protein signal transducers and
      activators of transcription 1 (Stat1) becomes phosphorylated on Y701, dimerizes,
      and accumulates in the nucleus to activate transcription of IFN-gamma-responsive
      genes. For maximal gene activation, S727 in the transcription activation domain
      of Stat1 also is inducibly phosphorylated by IFN-gamma. We previously purified a
      group of nuclear proteins that interact specifically with the Stat1 transcription
      activation domain. In this report, we identified one of them as the
      multifunctional Ca(2+)/calmodulin-dependent kinase (CaMK) II. We demonstrate that
      IFN-gamma mobilizes a Ca(2+) flux in cells and activates CaMKII. CaMKII can
      interact directly with Stat1 and phosphorylate Stat1 on S727 in vitro. Inhibition
      of Ca(2+) flux or CaMKII results in a lack of S727 phosphorylation and Stat1
      dependent gene activation, suggesting in vivo phosphorylation of Stat1 S727 by
      CaMKII. Thus two different cellular signaling events, IFN-gamma receptor
      occupation and Ca(2+) flux, are required for Stat1 to achieve maximal
      transcriptional activation through regulation of phosphorylation.

PMID- 11972024
TI  - Holding two heads together: stability of the myosin II rod measured by resonance
      energy transfer between the heads.
AB  - Myosin, similar to many molecular motors, is a two-headed dimer held together by
      a coiled-coiled rod. The stability of the coiled coil has implications for head
      head interactions, force generation, and possibly regulation. Here we used two
      different resonance energy transfer techniques to measure the distances between
      probes placed in the regulatory light chain of each head of a skeletal heavy
      meromyosin, near the head-rod junction (positions 2, 73, and 94). Our results
      indicate that the rod largely does not uncoil when myosin is free in solution,
      and at least beyond the first heptad, the subfragment 2 rod remains relatively
      intact even under the relatively large strain of two-headed myosin (rigor)
      binding to actin. We infer that uncoiling of the rod likely does not play a role
      in myosin II motility. To keep the head-rod junction intact, a distortion must
      occur within the myosin heads. This distortion may lead to different orientations
      of the light-chain domains within the myosin dimer when both heads are attached
      to actin, which would explain previously puzzling observations and require
      reinterpretation of others. In addition, by comparing resonance energy transfer
      techniques sensitive to different dynamical time scales, we find that the N
      terminus of the regulatory light chain is highly flexible, with possible
      implications for regulation. An intact rod may be a general property of molecular
      motors, because a similar conclusion has been reached recently for kinesin,
      although whether the rod remains intact will depend on the relative stiffness of
      the coiled coil and the head in different motors.

PMID- 11972025
TI  - Hemagglutinin sequence clusters and the antigenic evolution of influenza A virus.
AB  - Continual mutations to the hemagglutinin (HA) gene of influenza A virus generate
      novel antigenic strains that cause annual epidemics. Using a database of 560
      viral RNA sequences, we study the structure and tempo of HA evolution over the
      past two decades. We detect a critical length scale, in amino acid space, at
      which HA sequences aggregate into clusters, or swarms. We investigate the spatio
      temporal distribution of viral swarms and compare it to the time series of the
      influenza vaccines recommended by the World Health Organization. We introduce a
      method for predicting future dominant HA amino acid sequences and discuss its
      potential relevance to vaccine choice. We also investigate the relationship
      between cluster structure and the primary antibody-combining regions of the HA
      protein.

PMID- 11972027
TI  - Antioxidant-induced changes in oxidized DNA.
AB  - N-acetylcysteine (NAC), a strong antioxidant, has antigenotoxic and
      anticarcinogenic properties currently being investigated in clinical trials. NAC
      detoxifies free radicals (e.g., the hydroxyl radical,.OH) that cause DNA changes
      implicated in disease (e.g., cancer). The.OH reacts with purines to form
      mutagenic 8-hydroxypurine (8-OH) and putatively nonmutagenic formamidopyrimidine
      (Fapy) lesions. Fapy lesions inhibit DNA synthesis likely modulating the
      mutagenic potential of the 8-OH lesions, which would suggest that the ratio of
      these oxidized bases is biologically important. However, little is known about
      how NAC modifies oxidized DNA structure or how such modifications may affect
      cellular processes, such as replication and transcription. By using gas
      chromatography-mass spectrometry and Fourier transform-infrared spectroscopy, we
      found that dietary NAC (5% in the diet for 14 days) affected.OH-induced
      structural changes in DNA of the hind leg of the BALB/c mouse. For example,
      mutagenic 8-hydroxyguanine (8-OH-Gua) was reduced approximately 50% (P = 0.02) in
      mice fed NAC compared with controls. NAC reduced the log(10) (8-OH-Gua/FapyGua)
      ratio from 0.58 +/- 0.15 to essentially zero, a virtually neutral redox status.
      DNA from control mice had a remarkably high variance compared with mice fed NAC.
      Moreover, the DNA from treated and control mice was distinct with respect to base
      structure and vertical base-stacking interactions. The findings showing that NAC
      lowered the concentration of 8-OH-Gua, the log ratio, and the variance
      (previously associated with neoplastic changes) suggest that NAC reduces the
      mutagenic potential of oxidized DNA. These benefits could be offset by the other
      structural changes found after NAC exposure, which may affect the fidelity of DNA
      synthesis.

PMID- 11972026
TI  - A dynamic shift of VEGF isoforms with a transient and selective progesterone
      induced expression of VEGF189 regulates angiogenesis and vascular permeability in
      human uterus.
AB  - A key mechanism underlying physiological angiogenesis of the human endometrium is
      its ability to regenerate the vascular capillary network and to perform vascular
      remodeling (i.e., development of spiral arteries). Vascular endothelial growth
      factor (VEGF) is associated with angiogenesis and capillary permeability in this
      tissue. VEGF is expressed as several spliced variants, its main human isoforms
      contain 121 and 165 aa; 17beta-estradiol (E(2)) increases endometrial VEGF,
      possibly in all isoforms. Here we show that progesterone (P) selectively
      increases the expression of the VEGF(189) (V(189)) isoform in the human uterus.
      V(189) is identified in the conditioned medium of stromal cells treated with E(2)
      + P; its presence in this in vitro model of decidual stromal cells is detected
      after 6-8 days, using ELISA, and after 8-10 days, using Western blot analysis
      with different antibodies, including one specific for V(189). The secretion
      pattern of V(189) parallels that of the decidual protein IGFBP-1. V(189) is
      secreted as a native isoform, as compared with the migration of recombinant
      V(189) by SDS/PAGE. In situ hybridization and immunocytochemistry(,) performed on
      the same biopsies, suggest that decidual cells express V(189) during the mid-late
      secretory phase of the menstrual cycle and early gestation. Finally, using an in
      vivo permeability assay, we show that native V(189) increases capillary
      permeability. These observations demonstrate that P regulates V(189) expression
      in decidual cells, which could have important implications for understanding
      uterine vascular remodeling and implantation, and may be relevant in a range of
      disease states such as edema and irregular bleeding.

PMID- 11972028
TI  - Evidence for interpersonal violence in the St. Cesaire Neanderthal.
AB  - The St. Cesaire 1 Neanderthal skeleton of a young adult individual is unique in
      its association with Chatelperronian artifacts from a level dated to ca. 36,000
      years ago. Computer-tomographic imaging and computer-assisted reconstruction of
      the skull revealed a healed fracture in the cranial vault. When paleopathological
      and forensic diagnostic standards are applied, the bony scar bears direct
      evidence for the impact of a sharp implement, which was presumably directed
      toward the individual during an act of interpersonal violence. These findings add
      to the evidence that Neanderthals used implements not only for hunting and food
      processing, but also in other behavioral contexts. It is hypothesized that the
      high intra-group damage potential inherent to weapons might have represented a
      major factor during the evolution of hominid social behavior.

PMID- 11972029
TI  - From intestine to muscle: nuclear reprogramming through defective cloned embryos.
AB  - Nuclear transplantation is one of the very few ways by which the genetic content
      and capacity for nuclear reprogramming can be assessed in individual cells of
      differentiated somatic tissues. No more than 6% of the cells of differentiated
      tissues have thus far been shown to have nuclei that can be reprogrammed to
      elicit the formation of unrelated cell types. In Amphibia, about 25% of such
      nuclear transfers form morphologically abnormal partial blastulae that die within
      24 h. We have investigated the genetic content and capacity for reprogramming of
      those nuclei that generate partial blastulae, using as donors the intestinal
      epithelium cells of feeding Xenopus larvae. We have analyzed single nuclear
      transplant embryos obtained directly from intestinal tissue, thereby avoiding any
      genetic or epigenetic changes that might accumulate during cell culture. The
      expression of the intestine-specific gene intestinal fatty acid binding protein
      is extinguished by at least 10(4) times, within a few hours of nuclear
      transplantation. At the same time several genes that are normally expressed only
      in early embryos are very strongly activated in nuclear transplant embryos, but
      to an unregulated extent. Remarkably, cells from intestine-derived partial
      blastulae, when grafted to normal host embryos, contribute to several host
      tissues and participate in the normal 100-fold increase in axial muscle over
      several months. Thus, cells of defective cloned embryos unable to survive for
      more than 1 day can be reprogrammed to participate in new directions of
      differentiation and to maintain indefinite growth, despite the abnormal
      expression of early genes.

PMID- 11972030
TI  - Pituitary adenylate cyclase-activating polypeptide protects rat cerebellar
      granule neurons against ethanol-induced apoptotic cell death.
AB  - Alcohol exposure during development can cause brain malformations and
      neurobehavioral abnormalities. In view of the teratogenicity of ethanol,
      identification of molecules that could counteract the neurotoxic effects of
      alcohol deserves high priority. Here, we report that pituitary adenylate cyclase
      activating polypeptide (PACAP) can prevent the deleterious effect of ethanol on
      neuronal precursors. Exposure of cultured cerebellar granule cells to ethanol
      inhibited neurite outgrowth and provoked apoptotic cell death. Incubation of
      granule cells with PACAP prevented ethanol-induced apoptosis, and this effect was
      not mimicked by vasoactive intestinal polypeptide, suggesting that PAC1 receptors
      are involved in the neurotrophic activity of PACAP. Ethanol exposure induced a
      strong increase of caspase-2, -3, -6, -8, and -9 activities, DNA fragmentation,
      and mitochondrial permeability. Cotreatment of granule cells with PACAP provoked
      a significant inhibition of all of the apoptotic markers investigated although
      the neurotrophic activity of PACAP could only be ascribed to inhibition of
      caspase-3 and -6 activities. These data demonstrate that PACAP is a potent
      protective agent against ethanol-induced neuronal cell death. The fact that PACAP
      prevented ethanol toxicity even when added 2 h after alcohol exposure, suggests
      that selective PACAP agonists could have potential therapeutic value for the
      treatment of fetal alcohol syndrome.

PMID- 11972031
TI  - Chiral protein scissors: high enantiomeric selectivity for binding and its effect
      on protein photocleavage efficiency and specificity.
AB  - Chiral recognition of protein-binding sites by a simple organic molecule with
      selectivities >100 is reported here. The l-isomer of 4(1-pyrene)-3-butyroyl
      phenylalanine amide (Py-L-Phe) binds to BSA with an affinity constant (K(b)) of 3
      x 10(7) M(-1), whereas the corresponding D-isomer (Py-D-Phe) binds 100 times
      weaker. The enantiomers showed contrasting spectral changes when bound to BSA.
      Whereas hypochromism was observed with the L-isomer, hyperchromism was observed
      for the D-isomer, and, whereas the fluorescence of the L-isomer was quenched, the
      fluorescence of the D-isomer was enhanced. The induced CD spectra of the
      enantiomers bound to BSA bear a near mirror-image relationship. In contrast, the
      enantiomers show only moderate binding selectivity with lysozyme. The differences
      in the enantioselectivities with the two proteins indicate that the binding site
      of 4(1-pyrene)-3-butyroyl-phenylalanine amide (Py-Phe) in BSA is crowded, whereas
      that of lysozyme is more accommodative of either isomer. The enantioselective
      binding of Py-Phe isomers is further examined in protein photocleavage studies.
      Py-D-Phe cleaves BSA and lysozyme at a single site in a manner similar to Py-L
      Phe, but the cleavage yields are lower for the d-isomer. Sequencing of the
      resulting fragments indicated that the photocleavage sites of Py-D-Phe on BSA and
      lysozyme are identical to those of Py-L-Phe. Flash photolysis studies indicated
      only minor differences between the two enantiomers. The large binding
      selectivities, therefore, do not influence cleavage specificity or cleavage site
      location. The strong role of the single asymmetric center of Py-Phe in
      recognition and its minor role in photocleavage chemistry are demonstrated.

PMID- 11972032
TI  - Slowed conduction and ventricular tachycardia after targeted disruption of the
      cardiac sodium channel gene Scn5a.
AB  - Voltage-gated sodium channels drive the initial depolarization phase of the
      cardiac action potential and therefore critically determine conduction of
      excitation through the heart. In patients, deletions or loss-of-function
      mutations of the cardiac sodium channel gene, SCN5A, have been associated with a
      wide range of arrhythmias including bradycardia (heart rate slowing),
      atrioventricular conduction delay, and ventricular fibrillation. The
      pathophysiological basis of these clinical conditions is unresolved. Here we show
      that disruption of the mouse cardiac sodium channel gene, Scn5a, causes
      intrauterine lethality in homozygotes with severe defects in ventricular
      morphogenesis whereas heterozygotes show normal survival. Whole-cell patch clamp
      analyses of isolated ventricular myocytes from adult Scn5a(+/-) mice demonstrate
      a approximately 50% reduction in sodium conductance. Scn5a(+/-) hearts have
      several defects including impaired atrioventricular conduction, delayed
      intramyocardial conduction, increased ventricular refractoriness, and ventricular
      tachycardia with characteristics of reentrant excitation. These findings
      reconcile reduced activity of the cardiac sodium channel leading to slowed
      conduction with several apparently diverse clinical phenotypes, providing a model
      for the detailed analysis of the pathophysiology of arrhythmias.

PMID- 11972033
TI  - Cys-328 of IscS and Cys-63 of IscU are the sites of disulfide bridge formation in
      a covalently bound IscS/IscU complex: implications for the mechanism of iron
      sulfur cluster assembly.
AB  - IscS and IscU from Escherichia coli cooperate with each other in the biosynthesis
      of iron-sulfur clusters. IscS catalyzes the desulfurization of L-cysteine to
      produce L-alanine and sulfur. Cys-328 of IscS attacks the sulfur atom of L
      cysteine, and the sulfane sulfur derived from L-cysteine binds to the Sgamma atom
      of Cys-328. In the course of the cluster assembly, IscS and IscU form a covalent
      complex, and a sulfur atom derived from L-cysteine is transferred from IscS to
      IscU. The covalent complex is thought to be essential for the cluster biogenesis,
      but neither the nature of the bond connecting IscS and IscU nor the residues
      involved in the complex formation have been determined, which have thus far
      precluded the mechanistic analyses of the cluster assembly. We here report that a
      covalent bond is formed between Cys-328 of IscS and Cys-63 of IscU. The bond is a
      disulfide bond, not a polysulfide bond containing sulfane sulfur between the two
      cysteine residues. We also found that Cys-63 of IscU is essential for the IscU
      mediated activation of IscS: IscU induced a six-fold increase in the cysteine
      desulfurase activity of IscS, whereas the IscU mutant with a serine substitution
      for Cys-63 had no effect on the activity. Based on these findings, we propose a
      mechanism for an early stage of iron-sulfur cluster assembly: the sulfur transfer
      from IscS to IscU is initiated by the attack of Cys-63 of IscU on the Sgamma atom
      of Cys-328 of IscS that is bound to sulfane sulfur derived from L-cysteine.

PMID- 11972034
TI  - Altered sexual and social behaviors in trp2 mutant mice.
AB  - We have used gene targeting to generate mice with a homozygous deficiency in
      trp2, a cation channel expressed in the vomeronasal organ (VNO). Trp2 mutant
      animals reveal a striking reduction in the electrophysiological response to
      pheromones in the VNO, suggesting that trp2 plays a central role in mediating the
      pheromone response. These mutants therefore afford the opportunity to examine the
      role of the VNO in the generation of innate sexual and social behaviors in mice.
      Trp2 mutant males and nursing females are docile and fail to initiate aggressive
      attacks on intruder males. Male-female sexual behavior appears normal, but trp2
      mutant males also vigorously mount other males. These results suggest that the
      cation channel trp2 is required in the VNO to detect male-specific pheromones
      that elicit aggressive behaviors and dictate the choice of sexual partners.

PMID- 11972035
TI  - Animal antibiotic use has an early but important impact on the emergence of
      antibiotic resistance in human commensal bacteria.
AB  - Antibiotic use is known to promote the development of antibiotic resistance, but
      substantial controversy exists about the impact of agricultural antibiotic use
      (AAU) on the subsequent emergence of antibiotic-resistant bacteria among humans.
      AAU for animal growth promotion or for treatment or control of animal diseases
      generates reservoirs of antibiotic-resistant (AR) bacteria that contaminate
      animal food products. Mathematical models are an important tool for understanding
      the potential medical consequences of this increased exposure. We have developed
      a mathematical model to evaluate factors affecting the prevalence of human
      commensal AR bacteria that cause opportunistic infections (e.g., enterococci).
      Our analysis suggests that AAU hastens the appearance of AR bacteria in humans.
      Our model indicates that the greatest impact occurs very early in the emergence
      of resistance, when AR bacteria are rare, possibly below the detection limits of
      current surveillance methods.

PMID- 11972036
TI  - Human XPA and RPA DNA repair proteins participate in specific recognition of
      triplex-induced helical distortions.
AB  - Nucleotide excision repair (NER) plays a central role in maintaining genomic
      integrity by detecting and repairing a wide variety of DNA lesions. Xeroderma
      pigmentosum complementation group A protein (XPA) is an essential component of
      the repair machinery, and it is thought to be involved in the initial step as a
      DNA damage recognition and/or confirmation factor. Human replication protein A
      (RPA) and XPA have been reported to interact to form a DNA damage recognition
      complex with greater specificity for damaged DNA than XPA alone. The mechanism by
      which these two proteins recognize such a wide array of structures resulting from
      different types of DNA damage is not known. One possibility is that they
      recognize a common feature of the lesions, such as distortions of the helical
      backbone. We have tested this idea by determining whether human XPA and RPA
      proteins can recognize the helical distortions induced by a DNA triple helix, a
      noncanonical DNA structure that has been shown to induce DNA repair, mutagenesis,
      and recombination. We measured binding of XPA and RPA, together or separately, to
      substrates containing triplexes with three, two, or no strands covalently linked
      by psoralen conjugation and photoaddition. We found that RPA alone recognizes all
      covalent triplex structures, but also forms multivalent nonspecific DNA
      aggregates at higher concentrations. XPA by itself does not recognize the
      substrates, but it binds them in the presence of RPA. Addition of XPA decreases
      the nonspecific DNA aggregate formation. These results support the hypothesis
      that the NER machinery is targeted to helical distortions and demonstrate that
      RPA can recognize damaged DNA even without XPA.

PMID- 11972037
TI  - Otoancorin, an inner ear protein restricted to the interface between the apical
      surface of sensory epithelia and their overlying acellular gels, is defective in
      autosomal recessive deafness DFNB22.
AB  - A 3,673-bp murine cDNA predicted to encode a glycosylphosphatidylinositol
      anchored protein of 1,088 amino acids was isolated during a study aimed at
      identifying transcripts specifically expressed in the inner ear. This inner ear
      specific protein, otoancorin, shares weak homology with megakaryocyte
      potentiating factor/mesothelin precursor. Otoancorin is located at the interface
      between the apical surface of the inner ear sensory epithelia and their overlying
      acellular gels. In the cochlea, otoancorin is detected at two attachment zones of
      the tectorial membrane, a permanent one along the top of the spiral limbus and a
      transient one on the surface of the developing greater epithelial ridge. In the
      vestibule, otoancorin is present on the apical surface of nonsensory cells, where
      they contact the otoconial membranes and cupulae. The identification of the
      mutation (IVS12+2T>C) in the corresponding gene OTOA in one consanguineous
      Palestinian family affected by nonsyndromic recessive deafness DFNB22 assigns an
      essential function to otoancorin. We propose that otoancorin ensures the
      attachment of the inner ear acellular gels to the apical surface of the
      underlying nonsensory cells.

PMID- 11972038
TI  - Inclusion body myositis-like phenotype induced by transgenic overexpression of
      beta APP in skeletal muscle.
AB  - Inclusion body myositis (IBM), the most common age-related muscle disease in the
      elderly population, is an incurable disorder leading to severe disability.
      Sporadic IBM has an unknown etiology, although affected muscle fibers are
      characterized by many of the pathobiochemical alterations traditionally
      associated with neurodegenerative brain disorders such as Alzheimer's disease.
      Accumulation of the amyloid-beta peptide, which is derived from proteolysis of
      the larger amyloid-beta precursor protein (betaAPP), seems to be an early
      pathological event in Alzheimer's disease and also in IBM, where in the latter,
      it predominantly occurs intracellularly within affected myofibers. To elucidate
      the possible role of betaAPP mismetabolism in the pathogenesis of IBM, transgenic
      mice were derived in which we selectively targeted betaAPP overexpression to
      skeletal muscle by using the muscle creatine kinase promoter. Here we report that
      older (>10 months) transgenic mice exhibit intracellular immunoreactivity to
      betaAPP and its proteolytic derivatives in skeletal muscle. In this transgenic
      model, selective overexpression of betaAPP leads to the development of a subset
      of other histopathological and clinical features characteristic of IBM, including
      centric nuclei, inflammation, and deficiencies in motor performance. These
      results are consistent with a pathogenic role for betaAPP mismetabolism in human
      IBM.

PMID- 11972039
TI  - Evolution of the RNA polymerase II C-terminal domain.
AB  - In recent years a great deal of biochemical and genetic research has focused on
      the C-terminal domain (CTD) of the largest subunit (RPB1) of DNA-dependent RNA
      polymerase II. This strongly conserved domain of tandemly repeated heptapeptides
      has been linked functionally to important steps in the initiation and processing
      of mRNA transcripts in both animals and fungi. Although they are absolutely
      required for viability in these organisms, C-terminal tandem repeats do not occur
      in RPB1 sequences from diverse eukaryotic taxa. Here we present phylogenetic
      analyses of RPB1 sequences showing that canonical CTD heptads are strongly
      conserved in only a subset of eukaryotic groups, all apparently descended from a
      single common ancestor. Moreover, eukaryotic groups in which the most complex
      patterns of ontogenetic development occur are descended from this CTD-containing
      ancestor. Consistent with the results of genetic and biochemical investigations
      of CTD function, these analyses suggest that the enhanced control over RNA
      polymerase II transcription conveyed by acquired CTD/protein interactions was an
      important step in the evolution of intricate patterns of gene expression that are
      a hallmark of large, developmentally complex eukaryotic organisms.

PMID- 11972040
TI  - Functional role of internal water molecules in rhodopsin revealed by X-ray
      crystallography.
AB  - Activation of G protein-coupled receptors (GPCRs) is triggered and regulated by
      structural rearrangement of the transmembrane heptahelical bundle containing a
      number of highly conserved residues. In rhodopsin, a prototypical GPCR, the
      helical bundle accommodates an intrinsic inverse-agonist 11-cis-retinal, which
      undergoes photo-isomerization to the all-trans form upon light absorption. Such a
      trigger by the chromophore corresponds to binding of a diffusible ligand to other
      GPCRs. Here we have explored the functional role of water molecules in the
      transmembrane region of bovine rhodopsin by using x-ray diffraction to 2.6 A. The
      structural model suggests that water molecules, which were observed in the
      vicinity of highly conserved residues and in the retinal pocket, regulate the
      activity of rhodopsin-like GPCRs and spectral tuning in visual pigments,
      respectively. To confirm the physiological relevance of the structural findings,
      we conducted single-crystal microspectrophotometry on rhodopsin packed in our
      three-dimensional crystals and show that its spectroscopic properties are similar
      to those previously found by using bovine rhodopsin in suspension or membrane
      environment.

PMID- 11972041
TI  - Evolutionary recruitment of a flavin-dependent monooxygenase for the
      detoxification of host plant-acquired pyrrolizidine alkaloids in the alkaloid
      defended arctiid moth Tyria jacobaeae.
AB  - Larvae of Tyria jacobaeae feed solely upon the pyrrolizidine alkaloid-containing
      plant Senecio jacobaea. Ingested pyrrolizidine alkaloids (PAs), which are toxic
      to unspecialized insects and vertebrates, are efficiently N-oxidized in the
      hemolymph of T. jacobaeae by senecionine N-oxygenase (SNO), a flavin-dependent
      monooxygenase (FMO) with a high substrate specificity for PAs. Peptide
      microsequences obtained from purified T. jacobaeae SNO were used to clone the
      corresponding cDNA, which was expressed in active form in Escherichia coli. T.
      jacobaeae SNO possesses a signal peptide characteristic of extracellular
      proteins, and it belongs to a large family of mainly FMO-like sequences of mostly
      unknown function, including two predicted Drosophila melanogaster gene products.
      The data indicate that the gene for T. jacobaeae SNO, highly specific for toxic
      pyrrolizidine alkaloids, was recruited from a preexisting insect-specific FMO
      gene family of hitherto unknown function. The enzyme allows the larvae to feed on
      PA-containing plants and to accumulate predation-deterrent PAs in the hemolymph.

PMID- 11972043
TI  - A family of RRM-type RNA-binding proteins specific to plant mitochondria.
AB  - Expression of higher plant mitochondrial (mt) genes is regulated at the
      transcriptional, posttranscriptional, and translational levels, but the vast
      majority of the mtDNA and RNA-binding proteins involved remain to be identified.
      Plant mt single-stranded nucleic acid-binding proteins were purified by affinity
      chromatography, and corresponding genes have been identified. A majority of these
      proteins belong to a family of RNA-binding proteins characterized by the presence
      of an N-terminal RNA-recognition motif (RRM) sequence. They diverge in their C
      terminal sequences, suggesting that they can be involved in different plant mt
      regulation processes. Mitochondrial localization of the proteins was confirmed
      both in vitro and in vivo and by immunolocalization. Binding experiments showed
      that several proteins have a preference for poly(U)-rich sequences. This mt
      protein family contains the ubiquitous RRM motif and has no known mt counterpart
      in non-plant species. Phylogenetic and functional analysis suggest a common
      ancestor with RNA-binding glycine-rich proteins (GRP), a family of
      developmentally regulated proteins of unknown function. As with several plant,
      cyanobacteria, and animal proteins that have similar structures, the expression
      of one of the Arabidopsis thaliana mt RNA-binding protein genes is induced by low
      temperatures.

PMID- 11972042
TI  - Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and
      degeneration mimicking human dominant retinitis pigmentosa.
AB  - Rhodopsin is the G protein-coupled receptor that is activated by light and
      initiates the transduction cascade leading to night (rod) vision. Naturally
      occurring pathogenic rhodopsin (RHO) mutations have been previously identified
      only in humans and are a common cause of dominantly inherited blindness from
      retinal degeneration. We identified English Mastiff dogs with a naturally
      occurring dominant retinal degeneration and determined the cause to be a point
      mutation in the RHO gene (Thr4Arg). Dogs with this mutant allele manifest a
      retinal phenotype that closely mimics that in humans with RHO mutations. The
      phenotypic features shared by dog and man include a dramatically slowed time
      course of recovery of rod photoreceptor function after light exposure and a
      distinctive topographic pattern to the retinal degeneration. The canine disease
      offers opportunities to explore the basis of prolonged photoreceptor recovery
      after light in RHO mutations and determine whether there are links between the
      dysfunction and apoptotic retinal cell death. The RHO mutant dog also becomes the
      large animal needed for preclinical trials of therapies for a major subset of
      human retinopathies.

PMID- 11972045
TI  - Regulation of transcription by H1 phosphorylation in Tetrahymena is position
      independent and requires clustered sites.
AB  - In Tetrahymena cells, constitutive phosphorylation of histone H1 phenocopies the
      loss of H1 from chromatin. Regulation of transcription by H1 phosphorylation is
      achieved by altering the overall charges of a small domain. Here, we further
      explore the electrostatic properties of this domain and the mechanism by which it
      regulates transcription. We demonstrate that the regulatory effect of the
      clustered charges does not require any long-range interaction and is position
      independent. However, when the same number of charges was dispersed throughout
      the H1 molecule, the effect became undetectable. The results are explained by a
      nucleation-propagation model and provide in vivo evidence that the synergy of the
      clustered positive charges plays a role in histone function and gene regulation.

PMID- 11972044
TI  - Functional consequences of caspase activation in cardiac myocytes.
AB  - Cardiomyocyte apoptosis is present in many cardiac disease states, including
      heart failure and ischemic heart disease. Apoptosis is associated with the
      activation of caspases that mediate the cleavage of vital and structural
      proteins. However, the functional contribution of apoptosis to these conditions
      is not known. Furthermore, in cardiac myocytes, apoptosis may not be complete,
      allowing the cells to persist for a prolonged period within the myocardium.
      Therefore, we examined whether caspase-3 cleaved cardiac myofibrillar proteins
      and, if so, whether it affects contractile function. The effects of caspase-3
      were studied in vitro on individual components of the cardiac myofilament
      including alpha-actin, alpha-actinin, myosin heavy chain, myosin light chain 1/2,
      tropomyosin, cardiac troponins (T, I, C), and the trimeric troponin complex.
      Exposure of the myofibrillar protein (listed above) to caspase-3 for 4 h resulted
      in the cleavage of alpha-actin and alpha-actinin, but not myosin heavy chain,
      myosin light chain 1/2, and tropomyosin, into three fragments (30, 20, and 15
      kDa) and one major fragment (45 kDa), respectively. When cTnT, cTnI, and cTnC
      were incubated individually with caspase-3, there was no detectable cleavage.
      However, when the recombinant troponin complex was exposed to caspase-3, cTnT was
      cleaved, resulting in fragments of 25 kDa. Furthermore, rat cardiac myofilaments
      exposed to caspase-3 exhibited similar patterns of myofibrillar protein cleavage.
      Treatment with the caspase inhibitor DEVD-CHO or z-VAD-fmk abolished the
      cleavage. Myofilaments, isolated from adult rat ventricular myocytes after
      induction of apoptotic pathway by using beta-adrenergic stimulation, displayed a
      similar pattern of actin and TnT cleavage. Exposure of skinned fiber to caspase-3
      decreased maximal Ca(2+)-activated force and myofibrillar ATPase activity. Our
      results indicate that caspase-3 cleaved myofibrillar proteins, resulting in an
      impaired force/Ca(2+) relationship and myofibrillar ATPase activity. Induction of
      apoptosis in cardiac cells was associated with similar cleavage of myofilaments.
      Therefore, activation of apoptotic pathways may lead to contractile dysfunction
      before cell death.

PMID- 11972046
TI  - Interactions that determine the assembly of a retinoid X receptor/corepressor
      complex.
AB  - The retinoid X receptor (RXR) is a key regulator in multiple signaling pathways
      because it can form either a homodimer with itself or a heterodimer with members
      of the class I nuclear receptors. The RXR-containing dimers regulate
      transcription by recruiting coactivators or corepressors to the target promoters.
      The binding of coactivators to RXR is mediated through a hydrophobic pocket
      formed in part by the C-terminal activation helix (AF-2). However, little is
      known about interactions of corepressors with RXR and its roles in
      transcriptional repression. Here we show that the repression activity of RXR
      correlates with its binding to the corepressor silencing mediator for retinoid
      and thyroid hormone receptors (SMRT). This intrinsic repression activity is
      masked by the AF-2 helix, which antagonizes SMRT binding. Inhibition of SMRT
      binding by the AF-2 helix requires specific amino acid sequences and the helical
      structure. Furthermore, the SMRT-binding site on RXR is independent of helix 11
      but overlaps with the coactivator-binding pocket. On the basis of these results,
      we propose a structural model to help understand the molecular mechanism of
      corepressor recruitment by RXR.

PMID- 11972047
TI  - Conformational pathways in the gating of Escherichia coli mechanosensitive
      channel.
AB  - The pathway of the gating conformational transition of Escherichia coli
      mechanosensitive channel was simulated, using the recently modeled open and
      closed structures, by targeted molecular dynamics method. The transition can be
      roughly viewed as a four-stage process. The initial motion under a lower tension
      load is predominantly elastic deformation. The opening of the inner hydrophobic
      pore on a higher tension load takes place after the major expansion of the outer
      channel dimension. The hypothetical N-terminal S1 helical bundle has been
      confirmed to form the hydrophobic gate, together with the M1 helices. The
      sequential breaking of the tandem hydrophobic constrictions on the M1 and S1
      helices makes the two parts of the gate strictly coupled, acting as a single
      gate. The simulation also revealed that there is no significant energetic
      coupling between the inner S1 bundle and the outer M2 transmembrane helices. The
      molten-globular-like structural features of the S1 bundle in its intermediate
      open states may account for the observed multiple subconductance states.
      Moreover, the intermediate open states of mechanosensitive channels are not
      symmetric, i.e., the opening does not follow iris-like motion, which sharply
      contrasts to the potassium channel KcsA.

PMID- 11972049
TI  - Genetic basis for queen-worker dimorphism in a social insect.
AB  - Eusocial insects are characterized by reproductive division of labor, cooperative
      brood care, and the presence of a sterile worker caste. It is generally accepted
      that caste determination, including the differentiation of females into sterile
      workers and reproductive queens, is determined by environmental factors. In
      contrast, we find that in the red harvester ant, Pogonomyrmex barbatus, an
      individual's genotype at a particular microsatellite locus predicts its caste. We
      propose that this microsatellite locus is in tight linkage disequilibrium with at
      least one locus that plays an important role in caste determination. We call this
      the caste locus. We hypothesize that the system of caste determination we observe
      segregates the population into two distinct genetic lineages, each of which has
      distinct alleles at the microsatellite locus and also has distinct alleles, we
      propose, at caste. Workers are the offspring of parents from different lineages,
      and are thus heterozygous at caste, whereas queens are the offspring of parents
      from the same lineage, and are, therefore, homozygous at caste. This mode of
      caste determination has important consequences for the evolution of multiple
      mating by females and for control of the sex ratio and reproductive allocation in
      social insect colonies.

PMID- 11972048
TI  - Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis
      elegans.
AB  - Polyunsaturated fatty acids (PUFAs) are important membrane components and
      precursors of signaling molecules. To investigate the roles of these fatty acids
      in growth, development, and neurological function in an animal system, we
      isolated Caenorhabditis elegans mutants deficient in PUFA synthesis by direct
      analysis of fatty acid composition. C. elegans possesses all the desaturase and
      elongase activities to synthesize arachidonic acid and eicosapentaenoic acid from
      saturated fatty acid precursors. In our screen we identified mutants with defects
      in each fatty acid desaturation and elongation step of the PUFA biosynthetic
      pathway. The fatty acid compositions of the mutants reveal the substrate
      preferences of the desaturase and elongase enzymes and clearly demarcate the
      steps of this pathway. The mutants show that C. elegans does not require n3 or
      Delta5-unsaturated PUFAs for normal development under laboratory conditions.
      However, mutants with more severe PUFA deficiencies display growth and
      neurological defects. The mutants provide tools for investigating the roles of
      PUFAs in membrane biology and cell function in this animal model.

PMID- 11972050
TI  - cAMP facilitates EDHF-type relaxations in conduit arteries by enhancing
      electrotonic conduction via gap junctions.
AB  - We have investigated the role of cAMP in NO- and prostanoid-independent
      relaxations that are widely attributed to an endothelium-derived hyperpolarizing
      factor (EDHF). Under control conditions EDHF-type relaxations evoked by
      acetylcholine (ACh) in rabbit iliac arteries were transient, but in the presence
      of the cAMP phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) or the cell
      permeant cAMP analog 8-bromo-cAMP, relaxations became sustained with their maxima
      potentiated approximately 2-fold. Relaxation was associated with transient
      approximately 1.5-fold elevations in smooth muscle cAMP levels with both
      mechanical and nucleotide responses being abolished by interrupting gap
      junctional communication with the connexin-mimetic peptide Gap 27 and by
      endothelial denudation. However, IBMX induced a sustained endothelium-independent
      approximately 2-fold rise in cAMP levels, which was not further amplified by ACh,
      suggesting that the contribution of cAMP to the EDHF phenomenon is permissive.
      After selective loading of the endothelium with calcein AM, direct transfer of
      dye from the endothelium to the media was enhanced by IBMX or 8-bromo-cAMP, but
      not by 8-bromo-cGMP, whereas Gap 27 promoted sequestration within the intima. ACh
      induced hyperpolarizations of subintimal smooth muscle in arterial strips with
      intact endothelium were abolished by Gap 27 and the adenylyl cyclase inhibitor
      2',5'-dideoxyadenosine but were unaffected by IBMX. By contrast, in strips
      partially denuded of endothelium, IBMX enhanced the transmission of
      hyperpolarization from the endothelium to remote smooth muscle cells. These
      findings support the hypothesis that endothelial hyperpolarization underpins the
      EDHF phenomenon, with cAMP governing subsequent electrotonic signaling via both
      myoendothelial and homocellular smooth muscle gap junctions.

PMID- 11972051
TI  - Kinetics and mechanism of the DNA double helix invasion by pseudocomplementary
      peptide nucleic acids.
AB  - If adenines and thymines in two mutually complementary mixed-base peptide nucleic
      acid (PNA) oligomers are substituted with diaminopurines and thiouracils,
      respectively, so-called pseudocomplementary PNAs (pcPNAs) are created. Pairs of
      pcPNAs have recently demonstrated an ability to highly selectively target
      essentially any designated site on double-stranded DNA (dsDNA) by forming very
      stable PNA-DNA strand-displacement complexes via double duplex invasion (helix
      invasion). These properties of pcPNAs make them unique and very promising ligands
      capable of denying the access of DNA-binding proteins to dsDNA. To elucidate the
      sequence-unrestricted mechanism of sequence-specific dsDNA recognition by pcPNAs,
      we have studied the kinetics of formation of corresponding PNA-DNA complexes at
      various temperatures by the gel-shift assay. In parallel, the conditions for
      possible self-hybridization of pcPNA oligomers have been assayed by mixing curve
      (Job plot) and thermal melting experiments. The data indicate that, at
      physiological temperatures ( approximately 37 degrees C), the equilibrium is
      shifted toward the pairing of corresponding pcPNAs with each other. This finding
      explains a linear concentration dependence, within the submicromolar range, of
      the pcPNA invasion rate into dsDNA at 37 degrees C. At elevated temperatures (>50
      degrees C), the rather unstable pcPNA duplexes dissociate, yielding the expected
      quadratic dependence for the rate of pcPNA invasion on the PNA concentration. The
      polycationic character of pcPNA pairs, carrying the duplicated number of
      protonated terminal PNA residues commonly used to increase the PNA solubility and
      binding affinity, also explains the self-inhibition of pcPNA invasion observed at
      higher PNA concentrations. Melting of pcPNA duplexes occurs with the integral
      transition enthalpies ranged from -235 to -280 kJ.mol(-1), contributing to an
      anomalously high activation energy of approximately 150 kJ.mol(-1) found for the
      helix invasion of pcPNAs carrying four different nucleobases. A simplified
      kinetic model for pcPNAs helix invasion is proposed that interprets all unusual
      features of pcPNAs binding to dsDNA. Our findings have important implications for
      rational use of pcPNAs.

PMID- 11972052
TI  - YgbQ, a cell division protein in Escherichia coli and Vibrio cholerae, localizes
      in codependent fashion with FtsL to the division site.
AB  - YgbQ is a cell division protein in Escherichia coli and Vibrio cholerae. In E.
      coli the ygbQ gene was discovered as a result of a computer search of the E. coli
      genome designed to find potential interacting partners for cell division protein
      FtsL. In V. cholerae, ygbQ was identified as an essential gene by using a
      transposon that fuses genes to an arabinose promoter. The role of YgbQ in cell
      division is supported by the following. Cells depleted of YgbQ in both organisms
      form long filaments, but DNA segregation is not affected. YgbQ localizes to the
      constriction site in wild-type E. coli cells. Localization of E. coli YgbQ to the
      constriction site depends on cell division proteins FtsQ and FtsL but not FtsW
      and FtsI, placing YgbQ in the sequential dependency order of proteins localizing
      to the division site. Localization of green fluorescent protein-FtsL also depends
      on YgbQ, indicating that FtsL and YgbQ colocalize to the division site in E.
      coli. Our results show colocalization of proteins to the bacterial midcell in E.
      coli and raise the possibility that these proteins interact in a coiled-coil
      structure.

PMID- 11972054
TI  - IRF-3-dependent, NFkappa B- and JNK-independent activation of the 561 and IFN
      beta genes in response to double-stranded RNA.
AB  - Double-stranded (ds) RNA induces transcription of the 561 gene by activating IFN
      regulatory factor (IRF) transcription factors, whereas similar induction of the
      IFN-beta gene is thought to require additional activation of NFkappaB and AP-1.
      In mutant P2.1 cells, dsRNA failed to activate NFkappaB, IRF-3, p38, or c-Jun N
      terminal kinase, and transcription of neither 561 mRNA nor IFN-beta mRNA was
      induced. The defect in the IRF-3 pathway was traced to a low cellular level of
      this protein because of its higher rate of degradation in P2.1 cells. As
      anticipated, in several clonal derivatives of P2.1 cells expressing different
      levels of transfected IRF-3, activation of IRF-3 and induction of 561 mRNA by
      dsRNA was restored fully, although the defects in other responses to dsRNA
      persisted. Surprisingly, IFN-beta mRNA also was induced strongly in these cells
      in response to dsRNA, demonstrating that the activation of NFkappaB and AP-1 is
      not required. This conclusion was confirmed in wild-type cells overexpressing IRF
      3 by blocking NFkappaB activation with the IkappaB superrepressor and AP-1
      activation with a p38 inhibitor. Therefore, IRF-3 activation by dsRNA is
      sufficient to induce the transcription of genes with simple promoters such as 561
      as well as complex promoters such as IFN-beta.

PMID- 11972053
TI  - Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9.
AB  - Much is known about the transport of arsenite and antimonite into microbes, but
      the identities of mammalian transport proteins are unknown. The Saccharomyces
      cerevisiae FPS1 gene encodes a membrane protein homologous to the bacterial
      aquaglyceroporin GlpF and to mammalian aquaglyceroporins AQP7 and AQP9. Fps1p
      mediates glycerol uptake and glycerol efflux in response to hypoosmotic shock.
      Fps1p has been shown to facilitate uptake of the metalloids arsenite and
      antimonite, and the Escherichia coli homolog, GlpF, facilitates the uptake and
      sensitivity to metalloid salts. In this study, the ability of mammalian
      aquaglyceroporins AQP7 and AQP9 to substitute for the yeast Fps1p was examined.
      The fps1Delta strain of S. cerevisiae exhibits increased tolerance to arsenite
      and antimonite compared to a wild-type strain. Introduction of a plasmid
      containing AQP9 reverses the metalloid tolerance of the deletion strain. AQP7 was
      not expressed in yeast. The fps1Delta cells exhibit reduced transport of
      (73)As(III) or (125)Sb(III), but uptake is enhanced by expression of AQP9.
      Xenopus laevis oocytes microinjected with either AQP7 or AQP9 cRNA exhibited
      increased transport of (73)As(III). These results suggest that AQP9 and AQP7 may
      be a major routes of arsenite uptake into mammalian cells, an observation
      potentially of large importance for understanding the action of arsenite as a
      human toxin and carcinogen, as well as its efficacy as a chemotherapeutic agent
      for acute promyelocytic leukemia.

PMID- 11972055
TI  - Mechanisms of noise-resistance in genetic oscillators.
AB  - A wide range of organisms use circadian clocks to keep internal sense of daily
      time and regulate their behavior accordingly. Most of these clocks use
      intracellular genetic networks based on positive and negative regulatory
      elements. The integration of these "circuits" at the cellular level imposes
      strong constraints on their functioning and design. Here, we study a recently
      proposed model [Barkai, N. & Leibler, S. (2000) Nature (London), 403, 267-268]
      that incorporates just the essential elements found experimentally. We show that
      this type of oscillator is driven mainly by two elements: the concentration of a
      repressor protein and the dynamics of an activator protein forming an inactive
      complex with the repressor. Thus, the clock does not need to rely on mRNA
      dynamics to oscillate, which makes it especially resistant to fluctuations.
      Oscillations can be present even when the time average of the number of mRNA
      molecules goes below one. Under some conditions, this oscillator is not only
      resistant to but, paradoxically, also enhanced by the intrinsic biochemical
      noise.

PMID- 11972056
TI  - Oligo(dT) primer generates a high frequency of truncated cDNAs through internal
      poly(A) priming during reverse transcription.
AB  - We have analyzed a systematic flaw in the current system of gene identification:
      the oligo(dT) primer widely used for cDNA synthesis generates a high frequency of
      truncated cDNAs through internal poly(A) priming. Such truncated cDNAs may
      contribute to 12% of the expressed sequence tags in the current dbEST database.
      By using a synthetic transcript and real mRNA templates as models, we
      characterized the patterns of internal poly(A) priming by oligo(dT) primer. We
      further demonstrated that the internal poly(A) priming can be effectively
      diminished by replacing the oligo(dT) primer with a set of anchored oligo(dT)
      primers for reverse transcription. Our study indicates that cDNAs designed for
      genomewide gene identification should be synthesized by use of the anchored
      oligo(dT) primers, rather than the oligo(dT) primers, to diminish the generation
      of truncated cDNAs caused by internal poly(A) priming.

PMID- 11972057
TI  - MIP-1alpha, MIP-1beta, RANTES, and ATAC/lymphotactin function together with IFN
      gamma as type 1 cytokines.
AB  - We analyzed for the first time the expression of chemokines in subpopulations of
      the murine immune system at the single-cell level. We demonstrate in vitro and in
      a model of murine listeriosis that macrophage inflammatory protein (MIP)-1alpha,
      MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES),
      and activation-induced, T cell-derived, and chemokine-related cytokine
      (ATAC)/lymphotactin are cosecreted to a high degree with IFN-gamma by activated
      individual natural killer (NK), CD8(+) T, and CD4(+) T helper 1 (Th1) cells.
      Functionally, ATAC and the CC chemokines cooperate with IFN-gamma in the up
      regulation of CD40, IL-12, and tumor necrosis factor-alpha, molecules playing a
      central role in the effector phase of macrophages. Our data indicate that (i) MIP
      1alpha, MIP-1beta, RANTES, and ATAC are not only chemoattractants but also
      coactivators of macrophages, (ii) MIP-1alpha, MIP-1beta, RANTES, and ATAC
      constitute together with IFN-gamma a group of "type 1 cytokines," and (iii) these
      cytokines act together as a functional unit that is used by NK cells in the
      innate phase and then "handed over" to CD8(+) T cells in the antigen-specific
      phase of the immune defense, thus bridging the two components of a Th1 immune
      reaction.

PMID- 11972058
TI  - Association and regulation of casein kinase 2 activity by adenomatous polyposis
      coli protein.
AB  - Mutations in the adenomatous polyposis coli (APC) gene are responsible for
      familial adenomatous polyposis coli and also sporadic colorectal cancer
      development. By using antibodies raised against the N-terminal region of APC
      protein, we have detected the variable masses of endogenous APC proteins in
      individual cell lines established from human colorectal carcinomas caused by
      nonsense mutations of the gene. Phosphorylation of immunoprecipitates of full
      length and truncated APC were observed in in vitro kinase reaction, indicating
      association of APC with protein kinase activity. The kinase activity complexed
      with APC was sensitive to heparin and used GTP as phosphoryl donor, suggesting an
      involvement of casein kinase 2 (CK2). Both CK2alpha- and beta-subunits were found
      to associate with APC in immunoprecipitates as well as in pull-down assays, with
      preferential interaction of APC with tetrameric CK2 holoenzyme. In synchronized
      cell populations, the association of APC with CK2 was cell cycle dependent, with
      the highest association in G(2)/M. Unexpectedly, APC immunoprecipitates
      containing full-length APC protein inhibited CK2 in vitro, whereas
      immunoprecipitates of truncated APC had little effect. This was confirmed by
      using recombinant APC, and the inhibitory region was localized to the C terminus
      of APC between residues 2086 and 2394. Overexpression of this fragment in SW480
      cells suppressed cell proliferation rates as well as tumorigenesis. These results
      demonstrate a previously uncharacterized functional interaction between the tumor
      suppressor protein APC and CK2 and suggest that growth-inhibitory effects of APC
      may be regulated by inhibition of CK2.

PMID- 11972059
TI  - Organic semiconductors: a theoretical characterization of the basic parameters
      governing charge transport.
AB  - Organic semiconductors based on pi-conjugated oligomers and polymers constitute
      the active elements in new generations of plastic (opto)electronic devices. The
      performance of these devices depends largely on the efficiency of the charge
      transport processes; at the microscopic level, one of the major parameters
      governing the transport properties is the amplitude of the electronic transfer
      integrals between adjacent oligomer or polymer chains. Here, quantum-chemical
      calculations are performed on model systems to address the way transfer integrals
      between adjacent chains are affected by the nature and relative positions of the
      interacting units. Compounds under investigation include oligothienylenes,
      hexabenzocoronene, oligoacenes, and perylene. It is shown that the amplitude of
      the transfer integrals is extremely sensitive to the molecular packing.
      Interestingly, in contrast to conventional wisdom, specific arrangements can lead
      to electron mobilities that are larger than hole mobilities, which is, for
      instance, the case of perylene.

PMID- 11972060
TI  - RNA interference by expression of short-interfering RNAs and hairpin RNAs in
      mammalian cells.
AB  - Duplexes of 21-nt RNAs, known as short-interfering RNAs (siRNAs), efficiently
      inhibit gene expression by RNA interference (RNAi) when introduced into mammalian
      cells. We show that siRNAs can be synthesized by in vitro transcription with T7
      RNA polymerase, providing an economical alternative to chemical synthesis of
      siRNAs. By using this method, we show that short hairpin siRNAs can function like
      siRNA duplexes to inhibit gene expression in a sequence-specific manner. Further,
      we find that hairpin siRNAs or siRNAs expressed from an RNA polymerase III vector
      based on the mouse U6 RNA promoter can effectively inhibit gene expression in
      mammalian cells. U6-driven hairpin siRNAs dramatically reduced the expression of
      a neuron-specific beta-tubulin protein during the neuronal differentiation of
      mouse P19 cells, demonstrating that this approach should be useful for studies of
      differentiation and neurogenesis. We also observe that mismatches within hairpin
      siRNAs can increase the strand selectivity of a hairpin siRNA, which may reduce
      self-targeting of vectors expressing siRNAs. Use of hairpin siRNA expression
      vectors for RNAi should provide a rapid and versatile method for assessing gene
      function in mammalian cells, and may have applications in gene therapy.

PMID- 11972061
TI  - Interrogating protein interaction networks through structural biology.
AB  - Protein-protein interactions are central to most biological processes. Although
      much recent effort has been put into methods to identify interacting partners,
      there has been a limited focus on how these interactions compare with those known
      from three-dimensional (3D) structures. Because comparison of protein
      interactions often involves considering homologous, but not identical, proteins,
      a key issue is whether proteins that are homologous to an interacting pair will
      interact in the same way, or interact at all. Accordingly, we describe a method
      to test putative interactions on complexes of known 3D structure. Given a 3D
      complex and alignments of homologues of the interacting proteins, we assess the
      fit of any possible interacting pair on the complex by using empirical
      potentials. For studies of interacting protein families that show different
      specificities, the method provides a ranking of interacting pairs useful for
      prioritizing experiments. We evaluate the method on interacting families of
      proteins with multiple complex structures. We then consider the fibroblast growth
      factor/receptor system and explore the intersection between complexes of known
      structure and interactions proposed between yeast proteins by methods such as two
      hybrids. We provide confirmation for several interactions, in addition to
      suggesting molecular details of how they occur.

PMID- 11972062
TI  - Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage
      recruitment into tissues.
AB  - The ATP-binding cassette transporter 1 (ABCA1) has recently been identified as a
      key regulator of high-density lipoprotein (HDL) metabolism, which is defective in
      familial HDL-deficiency syndromes such as Tangier disease. ABCA1 functions as a
      facilitator of cellular cholesterol and phospholipid efflux, and its expression
      is induced during cholesterol uptake in macrophages. To assess the role of
      macrophage ABCA1 in atherosclerosis, we generated low-density lipoprotein (LDL)
      receptor knockout (LDLr(-/-)) mice that are selectively deficient in leukocyte
      ABCA1 (ABCA1(-/-)) by using bone marrow transfer (ABCA1(-/-) --> LDLr(-/-)). Here
      we demonstrate that ABCA1(-/-) --> LDLr(-/-) chimeras develop significantly
      larger and more advanced atherosclerotic lesions compared with chimeric LDLr(-/-)
      mice with functional ABCA1 in hematopoietic cells. Targeted disruption of
      leukocyte ABCA1 function did not affect plasma HDL cholesterol levels. The amount
      of macrophages in liver and spleen and peripheral blood leukocyte counts is
      increased in the ABCA1(-/-) --> LDLr(-/-) chimeras. Our results provide evidence
      that leukocyte ABCA1 plays a critical role in the protection against
      atherosclerosis, and we identify ABCA1 as a leukocyte factor that controls the
      recruitment of inflammatory cells.

PMID- 11972063
TI  - Interactions between thalamic and cortical rhythms during semantic memory recall
      in human.
AB  - Human scalp electroencephalographic rhythms, indicative of cortical population
      synchrony, have long been posited to reflect cognitive processing. Although
      numerous studies employing simultaneous thalamic and cortical electrode recording
      in nonhuman animals have explored the role of the thalamus in the modulation of
      cortical rhythms, direct evidence for thalamocortical modulation in human has
      not, to our knowledge, been obtained. We simultaneously recorded from thalamic
      and scalp electrodes in one human during performance of a cognitive task and
      found a spatially widespread, phase-locked, low-frequency rhythm (7-8 Hz) power
      decrease at thalamus and scalp during semantic memory recall. This low-frequency
      rhythm power decrease was followed by a spatially specific, phase-locked, fast
      rhythm (21-34 Hz) power increase at thalamus and occipital scalp. Such a pattern
      of thalamocortical activity reflects a plausible neural mechanism underlying
      semantic memory recall that may underlie other cognitive processes as well.

PMID- 11972064
TI  - Reconciling paleodistribution models and comparative phylogeography in the Wet
      Tropics rainforest land snail Gnarosophia bellendenkerensis (Brazier 1875).
AB  - Comparative phylogeography has proved useful for investigating biological
      responses to past climate change and is strongest when combined with extrinsic
      hypotheses derived from the fossil record or geology. However, the rarity of
      species with sufficient, spatially explicit fossil evidence restricts the
      application of this method. Here, we develop an alternative approach in which
      spatial models of predicted species distributions under serial paleoclimates are
      compared with a molecular phylogeography, in this case for a snail endemic to the
      rainforests of North Queensland, Australia. We also compare the phylogeography of
      the snail to those from several endemic vertebrates and use consilience across
      all of these approaches to enhance biogeographical inference for this rainforest
      fauna. The snail mtDNA phylogeography is consistent with predictions from
      paleoclimate modeling in relation to the location and size of climatic refugia
      through the late Pleistocene-Holocene and broad patterns of extinction and
      recolonization. There is general agreement between quantitative estimates of
      population expansion from sequence data (using likelihood and coalescent methods)
      vs. distributional modeling. The snail phylogeography represents a composite of
      both common and idiosyncratic patterns seen among vertebrates, reflecting the
      geographically finer scale of persistence and subdivision in the snail. In
      general, this multifaceted approach, combining spatially explicit
      paleoclimatological models and comparative phylogeography, provides a powerful
      approach to locating historical refugia and understanding species' responses to
      them.

PMID- 11972065
TI  - Precision and functional specificity in mRNA decay.
AB  - Posttranscriptional processing of mRNA is an integral component of the gene
      expression program. By using DNA microarrays, we precisely measured the decay of
      each yeast mRNA, after thermal inactivation of a temperature-sensitive RNA
      polymerase II. The half-lives varied widely, ranging from approximately 3 min to
      more than 90 min. We found no simple correlation between mRNA half-lives and ORF
      size, codon bias, ribosome density, or abundance. However, the decay rates of
      mRNAs encoding groups of proteins that act together in stoichiometric complexes
      were generally closely matched, and other evidence pointed to a more general
      relationship between physiological function and mRNA turnover rates. The results
      provide strong evidence that precise control of the decay of each mRNA is a
      fundamental feature of the gene expression program in yeast.

PMID- 11972067
TI  - An alternative carotenoid-to-bacteriochlorophyll energy transfer pathway in
      photosynthetic light harvesting.
AB  - Blue and green sunlight become available for photosynthetic energy conversion
      through the light-harvesting (LH) function of carotenoids, which involves
      transfer of carotenoid singlet excited states to nearby (bacterio)chlorophylls
      (BChls). The excited-state manifold of carotenoids usually is described in terms
      of two singlet states, S(1) and S(2), of which only the latter can be populated
      from the ground state by the absorption of one photon. Both states are capable of
      energy transfer to (B)Chl. We recently showed that in the LH1 complex of the
      purple bacterium Rhodospirillum rubrum, which is rather inefficient in carotenoid
      to-BChl energy transfer, a third additional carotenoid excited singlet state is
      formed. This state, which we termed S*, was found to be a precursor on an
      ultrafast fission reaction pathway to carotenoid triplet state formation. Here we
      present evidence that S* is formed with significant yield in the LH2 complex of
      Rhodobacter sphaeroides, which has a highly efficient carotenoid LH function. We
      demonstrate that S* is actively involved in the energy transfer process to BChl
      and thus have uncovered an alternative pathway of carotenoid-to-BChl energy
      transfer. In competition with energy transfer to BChl, fission occurs from S*,
      leading to ultrafast formation of carotenoid triplets. Analysis in terms of a
      kinetic model indicates that energy transfer through S* accounts for 10-15% of
      the total energy transfer to BChl, and that inclusion of this pathway is
      necessary to obtain a highly efficient LH function of carotenoids.

PMID- 11972066
TI  - The crystal structure of exonuclease RecJ bound to Mn2+ ion suggests how its
      characteristic motifs are involved in exonuclease activity.
AB  - RecJ, a 5' to 3' exonuclease specific for single-stranded DNA, functions in DNA
      repair and recombination systems. We determined the crystal structure of RecJ
      bound to Mn(2+) ion essential for its activity. RecJ has a novel fold in which
      two domains are interconnected by a long helix, forming a central groove. Mn(2+)
      is located on the wall of the groove and is coordinated by conserved residues
      characteristic of a family of phosphoesterases that includes RecJ proteins. The
      groove is composed of residues conserved among RecJ proteins and is positively
      charged. These findings and the narrow width of the groove indicate that the
      groove binds single- instead of double-stranded DNA.

PMID- 11972068
TI  - Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase
      cathepsin L.
AB  - Dilated cardiomyopathy is a frequent cause of heart failure and is associated
      with high mortality. Progressive remodeling of the myocardium leads to increased
      dimensions of heart chambers. The role of intracellular proteolysis in the
      progressive remodeling that underlies dilated cardiomyopathy has not received
      much attention yet. Here, we report that the lysosomal cysteine peptidase
      cathepsin L (CTSL) is critical for cardiac morphology and function. One-year-old
      CTSL-deficient mice show significant ventricular and atrial enlargement that is
      associated with a comparatively small increase in relative heart weight.
      Interstitial fibrosis and pleomorphic nuclei were found in the myocardium of the
      knockout mice. By electron microscopy, CTSL-deficient cardiomyocytes contained
      multiple large and apparently fused lysosomes characterized by storage of
      electron-dense heterogeneous material. Accordingly, the assessment of left
      ventricular function by echocardiography revealed severely impaired myocardial
      contraction in the CTSL-deficient mice. In addition, echocardiographic and
      electrocardiographic findings to some degree point to left ventricular
      hypertrophy that most likely represents an adaptive response to cardiac
      impairment. The histomorphological and functional alterations of CTSL-deficient
      hearts result in valve insufficiencies. Furthermore, abnormal heart rhythms, like
      supraventricular tachycardia, ventricular extrasystoles, and first-degree
      atrioventricular block, were detected in the CTSL-deficient mice.

PMID- 11972069
TI  - IL-15 mimics T cell receptor crosslinking in the induction of cellular
      proliferation, gene expression, and cytotoxicity in CD8+ memory T cells.
AB  - Generation of CD8(+) memory T cells requires antigenic stimulation through T cell
      receptor (TCR); however, maintenance of CD8(+) memory T cells seems to be
      mediated by cytokines, such as IL-15, in a TCR-independent manner. Compared with
      the TCR-induced activation, less is known about the mechanisms of IL-15 action.
      We report here a comparative and kinetic analysis of the responses of memory
      phenotype CD8(+) T cells to IL-15 or TCR (anti-CD3) stimulation in vitro. These
      two stimuli induce highly similar responses in memory phenotype CD8(+) T cells as
      measured by cellular proliferation, gene expression changes, synthesis of
      effector molecules (IFNgamma, tumor necrosis factor beta, granzyme B, and
      perforin), and induction of cytotoxicity. From 189 genes/expressed sequence tags
      (ESTs) whose expression changed in CD8(+) memory T cells after IL-15 and anti-CD3
      stimulation identified by cDNA microarray analysis, 77% of the genes/ESTs exhibit
      a highly similar pattern of expression between IL-15 and anti-CD3-treated cells,
      and only 16% and 7% of the genes/ESTs are differentially expressed in response to
      IL-15 and anti-CD3 treatments, respectively. These results show that IL-15 and
      anti-CD3 stimulation induced remarkably similar gene expression and effector
      function. Thus, IL-15 acts not only as a crucial growth factor but also as an
      antigen-independent activator of effector functions for CD8(+) memory T cells.

PMID- 11972070
TI  - Indirect reduction and plating of distal femoral nonunions.
AB  - OBJECTIVE: To observe and report the clinical results of indirect reduction and
      plating in the treatment of distal femoral nonunions. DESIGN: Prospective
      consecutive study. SETTING: Regional trauma center. PATIENTS: A consecutive
      series of twenty patients with nonunion of the distal femur, nineteen of whom had
      undergone operative initial fracture care. INTERVENTION: Surgical treatment with
      indirect reduction techniques using the 95-degree condylar blade-plate, condylar
      buttress plate, or locking condylar plate with autologous cancellous bone
      grafting in 45 percent of patients. Emphasis was placed on preoperative planning,
      intraoperative attention to soft tissue sparing, and selection of the
      appropriately applied implant to correct deformity, when present, and obtain
      union. MAIN OUTCOME MEASUREMENTS: Healing rate and time, operative blood loss and
      time, incidence of complications including instrumentation failure, loss of
      fixation, infection, and postoperative malalignment. Both the Bostman and
      Hospital for Special Surgery knee scores were used to quantify postoperative
      clinical results at an average follow-up of twenty-three months (range 12 to 60
      months). RESULTS: All twenty nonunions healed without further intervention at an
      average of fourteen weeks (range 12 to 20 weeks) postoperatively. There were no
      intraoperative complications. Average operative time was 154 minutes (range 90 to
      240 minutes), and blood loss was 245 milliliter (range 100 to 400 milliliters).
      Average Bostman knee score improved from eighteen to twenty-five points, and
      average Hospital for Special Surgery score improved from fifty-eight to eighty
      points. Average arc of knee motion improved from 92 to 110 degrees. There was no
      patient with significant postoperative axial or rotational malalignment (>5
      degrees) or limb length discrepancy (more than one centimeter). One patient with
      a history of osteomyelitis became infected postoperatively and healed without
      consequence after a debridement procedure. CONCLUSIONS: Contemporary plating
      techniques are effective in the treatment of distal femoral nonunions. Union
      occurred reliably with few complications, resulting in a majority of good or
      excellent clinical results.

PMID- 11972071
TI  - Iatrogenic nerve injury in acetabular fracture surgery: a comparison of monitored
      and unmonitored procedures.
AB  - OBJECTIVES: To review our experience with iatrogenic nerve injuries and to
      evaluate the efficacy of intraoperative monitoring in a large consecutive series
      of operatively treated acetabular fractures. DESIGN: Retrospective,
      nonrandomized. SETTING: Level I Trauma Center, January 1, 1992 through December
      31, 1998. PATIENTS/PARTICIPANTS: A total of 256 consecutive acetabular fractures
      were operatively treated at our institution; 140 unmonitored procedures and 112
      monitored procedures were available for review. The decision to use monitoring
      was at the discretion of the treating surgeon. INTERVENTION: Open reduction and
      internal fixation of the acetabular fracture. MAIN OUTCOME MEASUREMENT:
      Preoperative and postoperative neurologic examinations, fracture type, use of
      traction, dislocation, operative approach, and complications were analyzed. Motor
      strength, sensation, the need for gait aids, orthoses, and extent of recovery
      were evaluated. RESULTS: Traumatic nerve palsies were present in eleven of 140
      (7.9 percent) unmonitored and thirteen of 112 (11.6 percent) monitored fractures
      (p = 0.314). There were fourteen iatrogenic sciatic nerve palsies in 252 cases
      (5.6 percent). There were four iatrogenic sciatic palsies (2.9 percent) in the
      unmonitored group and ten iatrogenic palsies (8.9 percent) in the monitored group
      (p = 0.037). In the unmonitored group one of eighty-one Kocher-Langenbeck
      approaches (1.2 percent), two of fifty-two ilioinguinal (3.9 percent), and one of
      three extended iliofemoral approaches developed a sciatic palsy. In the monitored
      group six of seventy-seven Kocher-Langenbeck approaches (7.8 percent), three of
      twenty-five ilioinguinal (12 percent), and one of six combined approaches (16.7
      percent) developed a sciatic palsy. In seven of the ten iatrogenic palsies in the
      monitored group, the intraoperative monitoring was normal. Seventy-six patients
      were monitored with somatosensory evoked potential alone, and nine had iatrogenic
      injuries (11.8 percent). Thirty-six patients were monitored with somatosensory
      evoked potential and electromyography, and one had an iatrogenic injury (2.8
      percent) (p = 0.164). Clinical follow-up was available for three of the four
      patients with iatrogenic injuries in the unmonitored group, with a mean follow-up
      of twenty-seven months (range 8 to 60 months). Two patients had full motor
      recovery at a mean of six months, and one had no recovery at fourteen months.
      CONCLUSIONS: The use of intraoperative monitoring did not decrease the rate of
      iatrogenic sciatic palsy. Further study involving larger prospective, randomized
      methodology appears warranted. Sciatic nerve injury was more common in
      ilioinguinal approaches in both groups, likely due to reduction techniques for
      the posterior column performed with the hip flexed, placing the sciatic nerve
      under tension.

PMID- 11972072
TI  - The effect of augmentation with resorbable or conventional bone cement on the
      holding strength for femoral neck fracture devices.
AB  - OBJECTIVES: To compare maximum extraction torque and pull-out load for femoral
      neck fracture implants inserted with standard technique or after augmentation
      with polymethylmethacrylate (PMMA) or calcium phosphate cement (Norian SRS).
      DESIGN: Biomechanical study using synthetic bone. INTERVENTION: Implants were
      inserted in foam blocks with three different densities for simulation of normal
      bone or slight or severe osteoporosis. Tested implants included three screws (AO,
      Olmed, Hansson), one screw with both threads and a barb (Hybrid), and one pin
      with a hook (LIH hook-pin). Implants were inserted by standard technique and
      after augmentation with PMMA or Norian SRS. MAIN OUTCOME MEASUREMENT: The effect
      of (a) density of the synthetic bone (low, medium, high), (b) augmentation (none,
      PMMA, SRS), and (c) type of implant (AO, Olmed, Hansson, Hybrid, LIH) on the
      maximum extraction torque and pull-out load was determined using a material
      testing machine. Analysis of variance with Fisher's PLSD post hoc test was used
      to determine statistical differences. RESULTS: PMMA significantly increased
      maximum torque and pull-out load for all implants and block densities when
      compared without cement (p < 0.0001), whereas enhancement with SRS was far less
      pronounced and most obvious in low density blocks. For screws normally inserted
      without predrilling (Olmed and Hansson) the use of SRS in high density blocks
      caused a significant reduction in maximum torque (p < 0.0001) and pull-out load
      (p < 0.0001). SRS-augmented specimens failed through the cement at the periphery
      of the threads, whereas PMMA-augmented specimens failed between the cement and
      the synthetic bone. CONCLUSION: This study suggests that augmentation with PMMA
      around femoral neck fracture implants will increase the holding power
      significantly when compared with standard insertion technique as well as
      augmentation with calcium phosphate cement. Augmentation with calcium phosphate
      cement like SRS will increase the holding characteristics mainly in low density
      bone, whereas in high density bone it might even reduce the maximum torque
      because of the need for predrilling when using the cement for augmentation.

PMID- 11972073
TI  - A modified hip screw incorporating injected cement for the fixation of
      osteoporotic trochanteric fractures.
AB  - OBJECTIVE: To evaluate a modified sliding hip screw for the fixation of
      trochanteric fractures that provides increased fixation strength in osteoporotic
      bones and allows for the safe intraoperative application of bone cement. DESIGN:
      Biomechanical cadaver study. MATERIALS: Unstable trochanteric fractures were
      simulated by osteotomy in nine pairs of cadaveric femurs and stabilized by a
      standard sliding hip screw randomly assigned to the left or right femur. The
      contralateral femur was stabilized with a newly designed hip screw, which was
      augmented with low-viscosity bone cement. MAIN OUTCOME MEASUREMENTS: Femoral bone
      mineral density was measured by dual x-ray absorptiometry and quantitative
      computed tomography. Fixation stability of the hip was assessed after dynamic
      loading by displacement measurement of the femoral head in a simulated one-leg
      stance configuration. RESULTS: Modification of the hip screw together with cement
      augmentation significantly (p < 0.05) increased the initial stability of the
      fracture fixation technique. The total displacement of the femoral head was
      reduced by 39 percent on average using cement augmentation in the modified screw
      compared with the standard sliding hip screw. The largest improvement in initial
      fixation stability was found for the most osteoporotic bones. CONCLUSIONS: This
      modified hip screw augmented with bone cement can significantly enhance the
      initial fixation stability of trochanteric fractures in osteoporotic femurs.

PMID- 11972074
TI  - Unipolar versus bipolar hemiarthroplasty: functional outcome after femoral neck
      fracture at a minimum of thirty-six months of follow-up.
AB  - OBJECTIVES: This investigation was undertaken to compare a series of elderly
      individuals who sustained a displaced femoral neck fracture treated with either a
      cemented bipolar prosthesis or a cemented modular unipolar prosthesis. DESIGN: A
      retrospective review of prospectively collected data. SETTING: Hospital-based
      tertiary care orthopaedic trauma practice. PATIENTS AND PARTICIPANTS: Two hundred
      eighty-one community dwelling elderly patients sixty-five years of age or older
      who sustained a displaced femoral neck fracture (Garden Types III-IV) and
      underwent primary prosthetic replacement. INTERVENTION: One hundred one patients
      received a cemented bipolar prosthesis and 180 received a cemented modular
      unipolar prosthesis. MAIN OUTCOME MEASUREMENTS: The study was designed to
      determine whether there were any significant differences in: (a) the rate of
      prosthetic dislocation, postoperative medical and wound complications, or need
      for revision surgery, and (b) the functional outcome, including the incidence of
      hip pain and recovery of preinjury levels of ambulatory status and activities of
      daily living, at a minimum of thirty-six months of follow-up. RESULTS: The two
      groups of patients did not differ in preinjury characteristics (age, sex,
      American Society of Anesthesiologist rating of operative risk, number of
      comorbidities, fracture type, activities of daily living, ambulatory status).
      There were no significant differences in the rates of postoperative medical or
      wound complications or dislocation. Ninety-two patients died during the period of
      study. Forty patients were lost to follow-up or refused to participate.
      Consequently, 149 patients were followed for a minimum of thirty-six months.
      Functional ability was compared between both groups with regard to recovery of
      ambulatory status and activities of daily living, as well as the incidence of hip
      pain at a minimum of thirty-six months of follow-up. No significant differences
      were found between the unipolar and bipolar groups. CONCLUSION: Based on the
      results of this study, there does not appear to be any advantage to the use of a
      bipolar endoprosthesis in the management of displaced femoral neck fractures in
      the elderly. Furthermore, the extra cost of bipolar endoprostheses does not seem
      to warrant its use.

PMID- 11972075
TI  - Failure of fixation of tibial plateau fractures.
AB  - OBJECTIVE: To define the failure of fixation in tibial plateau fractures, detect
      its incidence, and determine the contributing factors. DESIGN: Mail survey and
      literature review were used to define the fixation failure; this definition was
      applied to a radiologic review of patients who were treated surgically for tibial
      plateau fracture at a Level 1 trauma unit for a three-year period from 1993 to
      1995. PATIENTS AND SETTING: Forty-two consecutive patients treated surgically at
      our trauma unit for tibial plateau fractures were studied retrospectively,
      specifically for loss of fixation. Factors that might affect the fracture
      fixation were reviewed, including age, mechanism of injury, type of fracture,
      bone quality, severity of fragmentation, severity of displacement, time to
      surgery, operating time, fixation method, use of bone graft, postoperative
      bracing, and mobilization. MAIN OUTCOME MEASURES: The main outcome measure was
      failure of fixation, by using criteria defined by the result of a mail survey of
      experts and literature review. RESULTS: Using a strict definition of radiologic
      failure of fixation, we reported an overall 31 percent rate of failure of
      fixation: 79 percent in patients older than sixty years compared with 7 percent
      in younger patients. The statistically significant associations with loss of
      reduction were age more than sixty years, premature weight bearing, preoperative
      displacement, fracture fragmentation, and severe osteoporosis. CONCLUSION: It is
      logical to define failure of fixation using the same measures considered as
      indications for reduction and fixation. Using these strict criteria, the
      incidence of radiologic failure was much higher than previous published series.
      In the elderly this was unacceptably high, and treatment goals should be limited
      to restoring stability and alignment.

PMID- 11972076
TI  - Magnetic resonance imaging of the multiple-ligament injured knee.
AB  - OBJECTIVE: To evaluate magnetic resonance imaging (MRI) and magnetic resonance
      angiography (MRA) in detecting soft tissue, neurovascular, and bony injury after
      multiple ligament knee injury, including knee dislocation. MATERIALS AND METHODS:
      A retrospective search was performed for patients presenting with reported knee
      dislocation from May 1993 through May 2000 who underwent both MRI and surgical
      reconstruction. Twenty-one patients met these criteria (15 men and six women; age
      range 14 to 75 years; mean 32.6 years). Magnetic resonance diagnoses of soft
      tissue and bony injury were compared with the patients' operative findings. MRA
      of the popliteal vessels was performed in seventeen of our twenty-one patients,
      and the results of these studies are described. RESULTS: Multiple ligamentous,
      tendinous, meniscal, chondral, osseous, and neural injuries were seen. There was
      excellent correlation (kappa > 0.8) between the magnetic resonance and operative
      findings with regard to the size and location of tears. Regarding meniscal tears,
      the type (e.g., bucket, radial split, meniscocapsular separation) and location
      correlated well with surgery. All ten nerve injuries noted on magnetic resonance
      were confirmed at surgery. Six of our patients had both conventional angiograms
      and MRAs with 100 percent agreement between the studies. In one patient an
      intimal flap in the popliteal artery was seen on MRA and confirmed on
      conventional angiographic images. CONCLUSION: MRI is an accurate method of
      assessing soft tissue, osseous, and neural damage after knee dislocation. Our
      early experience with popliteal fossa MRA is encouraging with complete agreement
      between the MRA and conventional angiography in patients who had both studies.

PMID- 11972077
TI  - The application of open intramedullary fixation in the treatment of pediatric
      radial and ulnar shaft fractures.
AB  - OBJECTIVES: This retrospective review evaluates the efficiency of standard
      intramedullary Kirschner wires for the treatment of unstable diaphyseal forearm
      fractures in children. DESIGN: Retrospective review. SETTING: Large teaching and
      research hospital in Turkey. PATIENTS: Thirty-one patients with diaphyseal
      forearm fractures were treated by surgical method between 1988 and 1998. The mean
      age was 12.3 years (range 7 to 17 years). The mean follow-up period was 4.2 years
      (1 to 6.2 years). INTERVENTION: The method of treatment of each forearm fracture
      was open reduction and intramedullary Kirschner wire fixation using a mini
      incision. MAIN OUTCOME MEASUREMENTS: Fracture union, growth disturbance of the
      forearm, and complications were evaluated. RESULTS: Union was obtained in all
      cases except two (6.4 percent). No forearm inequality was observed. CONCLUSIONS:
      Intramedullary fixation is a useful technique for unstable shaft fractures of the
      forearm in children that can not be treated by closed manipulation.

PMID- 11972079
TI  - Application of computer-generated stereolithography and interpositioning template
      in acetabular fractures: a report of eight cases.
AB  - To determine the effectiveness of stereolithography modeling technologies in the
      surgical treatment of complex acetabular fractures, five patients with a complex
      fracture of the acetabulum and three patients with posterior wall fractures were
      considered in this study. The patients were surgically treated using an
      interposition template for accurate positioning of the fixation plate and screw
      trajectories. Intraoperative fluoroscopy confirmed precise plate placement and
      that all screw trajectories missed the hip joint. Fluoroscopy was only needed for
      confirmation of fracture reduction and for confirmation of screw location.
      Application of a life-size stereolithographic model of the pelvis and an
      interpositioning template along with the computer model of the reversed
      nonfractured contralateral hemipelvis provides an effective means for
      preoperative planning and accurate fixation of acetabular fractures. Further
      studies with this type of preplanning equipment may show a decrease in operative
      time and morbidity, decrease in radiation exposure, and improvement in accuracy
      of plate and screw placement.

PMID- 11972078
TI  - Fluorescent tetracycline labeling as an aid to debridement of necrotic bone in
      the treatment of chronic osteomyelitis.
AB  - The authors have found that several months of preoperative tetracycline
      administration will label living bone so that it fluoresces under a blacklight
      during surgery. This allows intraoperative differentiation of viable bone from
      necrotic sequestra, which require removal in the treatment of chronic bone
      infection.

PMID- 11972080
TI  - Intramedullary plate fixation of a distal humerus fracture: a case report.
AB  - A case of a complex distal humeral fracture is presented. The patient lacked
      sufficient bony architecture to allow for conventional reconstruction. A
      technique is described using an intramedullary plate to obtain bony stabilization
      and permit early range of motion exercises.

PMID- 11972081
TI  - Endosteal substitution with an allograft cortical strut in the treatment of a
      periprosthetic femur fracture: a case report.
AB  - The use of allograft cortical struts in the treatment of periprosthetic fractures
      of the femur has been well described. Allograft struts are used to supplement
      cerclage wire fixation or may be placed outside the cortex opposite plate and
      screw fixation to improve screw fixation in osteoporotic bone. This generally
      requires extensive soft tissue stripping and may lead to delayed bony union. A
      technique is described wherein an allograft strut was inserted into the medullary
      canal through the fracture site and used as an endosteal substitution for
      osteoporotic cortical bone. This technique can improve screw fixation in
      osteoporotic bone while avoiding devascularization of the fractured femur.

PMID- 11972082
TI  - Fracture of the ankle associated with rupture of the Achilles tendon: case report
      and review of the literature.
AB  - SUMMARY: A thirty-five-year-old man fell two meters from a ladder and sustained a
      closed fracture of the medial malleolus with an ipsilateral complete Achilles
      tendon rupture. The Achilles tendon rupture was diagnosed by means of the
      patient's complaints and physical findings. The ankle fracture was diagnosed
      incidentally on routine radiographs. Such a combination of injuries has been
      reported infrequently in the literature, and striking similarities have been
      described in the mechanism of injury and fracture pattern. Remarkably, in three
      of four reports the combined injury was initially misdiagnosed.

PMID- 11972083
TI  - Use of C-clamps and pelvic packing to control hemorrhage after pelvic fracture.

PMID- 11972084
TI  - Prospective randomized controlled trial of an intramedullary nail versus dynamic
      screw and plate of intertrochanteric fractures of the femur.

PMID- 11972085
TI  - Failure of external fixation bone screws in a head injury.

PMID- 11972086
TI  - Early pin failure following external femoral fracture fixation in a head-injured
      child.

PMID- 11972089
TI  - Predictors of outcome in sickle cell disease.

PMID- 11972090
TI  - Ocular preservation after 36 Gy external beam radiation therapy for
      retinoblastoma.
AB  - PURPOSE: The purpose of this study was to document the ocular preservation rate
      after 36 Gy external beam radiation therapy (EBRT) for retinoblastoma. PATIENTS
      AND METHODS: Forty-nine eyes of 38 patients were treated with a median dose of 36
      Gy EBRT. The patient population included 7 unilateral and 31 bilateral
      presentations, with a median age at diagnosis of 4 months. Eyes enucleated at the
      time of diagnosis or treated with other measures were not included in the
      analysis of ocular preservation. The median age at EBRT was 8 months. Patients
      were monitored for progression of disease after EBRT and second malignant
      neoplasms. RESULTS: The median follow-up was 88.6 months, with an estimated
      ocular preservation rate of 82.0% +/- 5% at 10 years. There was a difference in
      the ocular preservation rates for patients with advanced disease (Reese-Ellsworth
      group III-V) compared with early disease. Metastatic disease developed in two
      patients, and a second malignant neoplasm developed in three. Patients treated
      with en face electrons experienced a lower 5-year estimate of ocular preservation
      than those treated with photons, although patients treated with electrons were
      more likely to have advanced disease. CONCLUSIONS: The use of low-dose EBRT (36
      Gy) results in ocular preservation rates that are comparable to those of high
      dose EBRT. The use of electrons requires careful treatment planning and
      computerized dosimetry.

PMID- 11972091
TI  - Treatment of refractory osteosarcoma with fractionated cyclophosphamide and
      etoposide.
AB  - PURPOSE: Standard multiagent chemotherapy for osteosarcoma may include platinum
      compounds, doxorubicin, and high-dose methotrexate. By identifying new
      chemotherapeutic strategies, the outcome of these patients can be improved and
      the toxicity of treatment regimens decreased. PATIENTS AND METHODS: The authors
      evaluated the activity of the combination of cyclophosphamide (500 mg/m2 per day
      for 5 days) and etoposide (100 mg/m2 per day for 5 days) given with granulocyte
      colony-stimulating factor (G-CSF) to children with osteosarcoma unresponsive to
      conventional treatment. RESULTS: Fourteen patients with refractory osteosarcoma
      were treated with this combination. Twelve patients had been previously treated
      with a multiagent regimen that included carboplatin, ifosfamide, methotrexate,
      and doxorubicin. Seven of 11 evaluable patients had a poor histologic response in
      their primary tumor at the time of definitive surgery (Huvos grade 1 or 2). Sites
      of relapse included lung, bone, and brain. A total of 47 courses were given. An
      overall response rate of 28.5% was achieved. A complete response was obtained in
      one patient (7.1%), a partial response was obtained in three patients (21.4%),
      and stable disease for 1 to 4 months was achieved in five patients (35.7%). Five
      patients (35.7%) had progressive disease. Grade 4 neutropenia was the primary
      form of toxicity observed; the median duration of absolute neurophil count less
      than 500/microL was 4 days. CONCLUSIONS: The combination of cyclophosphamide and
      etoposide resulted in a response rate of 28.5% in patients with refractory or
      relapsed osteosarcoma, and its incorporation into front-line therapies deserves
      further evaluation.

PMID- 11972092
TI  - Value of electronic data for model validation and refinement: bacteremia risk in
      children with fever and neutropenia.
AB  - BACKGROUND: Validating published risk models in a different time and setting can
      be a labor-intensive process. Data in electronic format provide the potential to
      test the validity of risk models without labor-intensive chart reviews and data
      capture. The authors attempted to use readily available electronic data to find
      appropriate cases and to validate and refine a previously developed risk model
      for predicting bacteremia in children with cancer who had fever and neutropenia.
      PATIENTS AND METHODS: By applying a largely automated case-finding algorithm to
      linked, electronic clinical and administrative data systems, the authors
      identified and acquired data regarding 157 episodes of fever and neutropenia in
      children with cancer admitted to a children's hospital during an 11-month period
      in 1997. The authors applied a previously developed and validated risk model for
      bacteremia to this 1997 cohort by assessing the odds ratios among risk groups.
      The model assigns encounters with absolute monocyte count of 100 cells or
      more/mm3 to a low-risk group and encounters with an absolute monocyte count of
      less than 100 cells/mm3 to intermediate-risk (temperature <39.0 degrees C) or
      high-risk (> or = 39.0 degrees C) groups. In addition, the authors explored
      whether the new data would have generated the same model. Univariate and
      multivariable analyses were performed to determine whether there were additional
      independent predictors of bacteremia. Recursive partitioning of admission
      absolute monocyte count and temperature was used to assess whether similar
      cutpoints would be found. RESULTS: There were 12 episodes of bacteremia (7.6%)
      among the 157 encounters. The previously developed model correctly predicted
      increasing rates of bacteremia in this 1997 cohort, ranging from 2.5% in the low
      risk group (one episode in a child with an infected central line) to 24% in the
      high-risk group. The odds ratio for the high-risk versus intermediate-risk group
      was 4.09 (95% confidence interval 1.05-15.91), comparable to the odds ratio of
      3.96 in the previously published derivation cohort (95% confidence interval 1.4
      11.1). Multivariate analysis of the new data revealed no independent risk factors
      for bacteremia other than admission absolute monocyte count and temperature.
      Recursive partitioning of absolute monocyte count and temperature generated risk
      categories that were somewhat different from those of the original model. The new
      data yielded three categories: low risk (temperature < or = 39.5 degrees C and
      absolute monocyte count >10/mm3), intermediate risk (temperature < or = 39.5
      degrees C and absolute monocyte count < or = 10/mm3), and high risk (temperature
      >39.5 degrees C). CONCLUSIONS: Existing electronic data provide an efficient
      means for case-finding and model validation and refinement. The previously
      developed bacteremia model had good but not optimal predictive performance in the
      new data set. Admission absolute monocyte count and temperature remain
      significant risk factors for bacteremia. Redefining the risk categories,
      including a much lower cutpoint for admission absolute monocyte count, improved
      the model's discrimination, which suggests that predictive models need periodic
      updating.

PMID- 11972093
TI  - Modeling administrative outcomes in fever and neutropenia: clinical variables
      significantly influence length of stay and hospital charges.
AB  - BACKGROUND: Administrative outcomes such as length of stay and charges are used
      to compare the quality of care across institutions and among individual
      providers. Clinical variables representing disease severity may explain some of
      the variability in these outcomes. OBJECTIVE: To determine the extent to which
      readily available clinical data can explain the variability in length of stay and
      charges for children with cancer admitted to the hospital for fever and
      neutropenia, and to assess the appropriateness of using a time-efficient
      electronic case-finding strategy for the development of administrative outcome
      models. METHODS: A retrospective cohort of 157 fever and neutropenia encounters
      in a single institution during 11 months in 1997 was identified using a largely
      automated case-finding strategy followed by independent, blinded review of the
      selected discharge summaries. Models of admission variables predicting log length
      of stay and log charges were developed using multiple linear regression. The
      "smearing" technique of Duan adjusted for logarithmic retransformation was used
      in calculating each subject's predicted length of stay and charges. R2 values
      were calculated. There were two secondary analyses. In one, the result of
      admission blood culture was entered as a potential covariate. In the second, to
      evaluate the appropriateness of basing models on automated case-finding without
      discharge summary review, the authors rederived the models using all of the
      encounters (n = 160) identified by the algorithm, which had included three false
      positive cases. RESULTS: Mean length of stay was 6.45 days. Mean charges were
      $11,967. Absolute monocyte count at admission was a significant, independent
      negative predictor of length of stay and charges. Underlying cancer diagnosis
      also was significant. Charges were highest for acute myeloid leukemia, followed
      by central nervous system tumors, other solid tumors, and acute lymphoblastic
      leukemia and lymphomas. Length of stay was highest for acute myeloid leukemia,
      followed by central nervous system tumors, acute lymphoblastic leukemia and
      lymphomas, and other solid tumors. Absolute monocyte count and tumor type were
      the major components of the model, but admission temperature (for both
      administrative outcomes) and the presence of localized infection (for length of
      stay) also were significant predictors. R2 values were 35.3% (charges) and 38.5%
      (length of stay), with validation R2 values of 26.6% and 29.2%, respectively.
      Entering bacteremia as a covariate improved the models. Inclusion of the three
      false-positive cases generated models with only a modest loss of accuracy; it
      introduced over-and underreporting of some of the less significant predictors but
      did not disrupt the ability to identify the major predictors, absolute monocyte
      count and tumor type. CONCLUSIONS: The clinical variables that were significant
      in this study account, in validation R2 estimates, for more than 25% of the
      variability in administrative outcomes for encounters of fever and neutropenia.
      Adjusting length of stay and charges for these clinical variables would allow for
      a fairer comparison of institutions and individual providers. The electronic case
      finding algorithm served as an efficient way to identify absolute monocyte count
      and tumor type as the major predictors and provided a conservative estimate of
      R2.

PMID- 11972094
TI  - Lymphocyte-predominant Hodgkin disease in children.
AB  - PURPOSE: To describe the clinicobiological features, treatment, treatment
      outcome, and sequelae of children with lymphocyte-predominant Hodgkin disease.
      PATIENTS AND METHODS: The authors performed a retrospective chart review of 754
      patients with Hodgkin disease diagnoses at New York Medical College and St. Jude
      Children's Research Hospital from 1962 to 2000 to identify those with lymphocyte
      predominant histology. Hematopathologists at the treating institutions reviewed
      stored tissue specimens and reconfirmed the histopathology of each case. RESULTS:
      Fifty-one children (44 boys, 7 girls) were identified. The median age was 10.5
      years (range 3.2-18.5); five children were younger than age 60 months. The median
      duration of lymphadenopathy before diagnosis was 4 months (range 0.5-30). Thirty
      six children had stage 1 disease, eight had stage 2 disease, four had stage 3
      disease, and three had stage 4 disease. Fifteen children underwent staging
      laparotomy, and four of these were upstaged. Treatment comprised combined
      modality therapy (n = 27), radiation therapy alone (n = 17), and chemotherapy
      alone (n = 7). Four children had a Hodgkin disease recurrence. Forty-eight (94%)
      patients were alive and disease-free at a median follow-up of 8 years (range 0.4
      32.6). Eleven patients had long-term, therapy-related adverse effects (cardiac,
      infertility, pulmonary, and second malignant neoplasms). Three patients died. Two
      died of complications of second malignant neoplasms and one died of infectious
      complications after Hodgkin disease recurrence. CONCLUSIONS: Children with
      lymphocyte-predominant Hodgkin disease respond favorably to a variety of
      treatment modalities and are ideal candidates for less toxic therapy.

PMID- 11972096
TI  - Predictors of bacteremia in febrile children with sickle cell disease.
AB  - PURPOSE: Bacteremia is an important cause of death and complications in children
      with sickle cell disease (SCD), yet predictors of bacteremia in these patients
      have not been well identified. The purpose of this study was to test whether
      clinical and hematologic variables commonly used to predict bacteremia in normal
      young children with fever could accurately predict bacteremia in febrile children
      with SCD. PATIENTS AND METHODS: The authors reviewed the medical records of all
      patients with SCD younger than 18 years of age over a 10-year period at a single
      institution for febrile events. They tested the univariate associations of age,
      height of fever, white blood cell count (WBC), absolute neutrophil count (ANC),
      and absolute band count (ABC) with bacteremia. Three separate multivariate
      analyses were performed using the predictor variables age, temperature, and one
      of three hematologic variables (ANC, WBC, or ABC) with the outcome bacteremia.
      RESULTS: There were 175 evaluable febrile events, of which 8 (4.6%) were
      associated with bacteremia. In the multivariate analyses, all hematologic
      variables, but not age or height of fever, retained significant associations with
      bacteremia. CONCLUSIONS: In febrile children with SCD, WBC, ANC, and ABC are all
      independently associated with bacteremia when adjusting for height of fever and
      age. Hematologic variables may be useful in developing prediction algorithms to
      identify febrile patients with SCD at higher risk of bacteremia. These data
      emphasize the need for a national trial to develop a predictive model with
      defined thresholds.

PMID- 11972095
TI  - Intrathecal thiotepa: reappraisal of an established therapy.
AB  - PURPOSE: Intrathecal thiotepa is recommended as a treatment of leptomeningeal
      metastases (LM) in children, although published data to support this approach are
      limited. The authors sought to determine the efficacy of intrathecal thiotepa for
      pediatric LM. PATIENTS AND METHODS: The authors reviewed all children treated
      with intrathecal thiotepa for LM at two tertiary children's hospitals, assessing
      outcome by cerebrospinal fluid cytology, neuroimaging, neurologic examination,
      and overall survival rate. RESULTS: Fifteen children with LM evidenced by
      malignant cells in the cerebrospinal fluid (mean age 7.3 years; five
      medulloblastoma, one anaplastic astrocytoma, one glioblastoma, one
      retinoblastoma, one neuroblastoma, two rhabdomyosarcoma, one non-Hodgkin
      lymphoma, two acute lymphoblastic leukemia, and one acute myelogenous leukemia)
      were treated with intrathecal thiotepa at 5 to 11.5 mg/m2 per dose for two to
      seven doses. Five children received concomitant craniospinal irradiation; 12
      received simultaneous systemic or other intrathecal chemotherapy, or both. Four
      children experienced clearance of malignant cells from the spinal fluid, but this
      response was sustained in only two. All four children with cytologic response
      received concurrent radiotherapy, chemotherapy, or both. No patients showed
      partial or complete response on neuroimaging. Only one child had improvement on
      the neurologic examination; six were unchanged and eight had worsening neurologic
      signs. Median survival was 15.1 weeks, with a 1-year overall survival rate of
      26.7% (standard error 11.4%). CONCLUSIONS: The unfavorable outcomes observed
      suggest that intrathecal thiotepa adds little to combination therapy for
      pediatric LM.

PMID- 11972098
TI  - Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia.
AB  - PURPOSE: To determine the prevalence of hypoparathyroidism in transfusion
      dependent patients with beta-thalassemia. PATIENTS AND METHODS: A total of 28
      transfusion-dependent patients with beta-thalassemia were interviewed, and their
      serum calcium, phosphate, magnesium, and intact parathyroid hormone levels were
      checked. Serum ferritin levels were measured to monitor the effect of chelation
      therapy. Blood urea nitrogen, creatinine, total protein, and albumin were
      measured in patients with undetectable or low intact parathyroid hormone levels.
      RESULTS: The prevalence of hypoparathyroidism was 10.7% (3/28). Mean age at
      diagnosis was 18 years. The serum ferritin levels of patients with
      hypoparathyroidism were 1,032, 2,102, and 7,680 microg/L. Only one patient had
      clinical symptoms of hypocalcemia. All three of the patients with
      hypoparathyroidism had hypogonadism, and 66.7% (2/3) of the patients had insulin
      dependent diabetes mellitus. CONCLUSIONS: Hypoparathyroidism in transfusion
      dependent patients with beta-thalassemia seems to be accompanied by other
      endocrinopathies. Serum ferritin may not have been a reliable indicator of iron
      overload in the three patients with hypoparathyroidism. Severe iron overload
      would easily explain these multiple endocrinopathies. This pattern is commonly
      seen in iron-overloaded patients with thalassemia elsewhere.

PMID- 11972097
TI  - Longitudinal changes in ferritin during chronic transfusion: a report from the
      Stroke Prevention Trial in Sickle Cell Anemia (STOP).
AB  - PURPOSE: Chronic red cell transfusion has been used for prevention of recurrent
      stroke in patients with sickle cell disease for three decades, and its
      effectiveness in primary prevention was recently shown. Iron overload, the
      inevitable result of chronic transfusion, is commonly monitored with serum
      ferritin concentration. PATIENTS AND METHODS: Sixty-one patients at high risk for
      stroke received chronic transfusion in a clinical trial of stroke prevention. A
      serum ferritin level of less than 500 ng/mL was required for study entry.
      Ferritin levels were obtained quarterly. Fifty patients who had four or more
      ferritin measurements were included in this analysis. Transfusions were
      administered as exchange or simple, with washed, reconstituted, or packed red
      blood cells, at the discretion of the site investigator. RESULTS: Serum ferritin
      levels increased linearly with cumulative transfusion volume during the first
      four ferritin measurements, but the rate of increase varied widely among
      patients. Rates of increase varied similarly among 23 patients who received
      exclusively simple transfusion with packed red cells and in five patients who
      received exchange transfusions. Thirty-two patients received a total transfusion
      volume of more than 250 mL/kg. Ferritin continued to increase linearly after the
      first four measurements in 14, but the remaining 18 experienced a plateau before
      the level reached 3,000 ng/mL. Six of those with a linear increase never reached
      a ferritin level of 3,000 ng/dL. CONCLUSIONS: There was strong intrapatient
      correlation between serum ferritin levels and volume transfused but wide
      interpatient variability early during chronic transfusion therapy. Intrapatient
      correlation declined at transfusion volumes of more than 250 mL/kg. Direct iron
      store assessment is needed to determine the clinical significance of serum
      ferritin variability.

PMID- 11972099
TI  - Transient erythroblastopenia of childhood: prospective study of 10 patients with
      special reference to viral infections.
AB  - PURPOSE: It has been proposed that human parvovirus B19 or human herpesvirus 6
      (HHV-6) causes transient erythroblastopenia of childhood (TEC). This study was
      performed prospectively and accurately in a sufficiently large population to
      confirm or reject these suggestions, or possibly to find another causative agent
      for TEC. PATIENTS AND METHODS: The authors studied prospectively the causative
      aspects of 10 consecutive children with TEC presenting at five Swedish pediatric
      clinics from 1994 to 1998 using serologic assays and polymerase chain reaction
      assays for B19, HHV-6, cytomegalovirus, and Epstein-Barr virus (EBV). The authors
      also performed isolation investigations of virus from bone marrow, stools, and
      aspirate from the nasopharynx. RESULTS: The authors found acute EBV infection in
      one child. There were no other instances of IgM positivity for any viruses at
      presentation, but a few children did show IgG positivity to HHV-6 (n = 2), EBV (n
      = 1), and cytomegalovirus (n = 1). No children were positive with respect to IgG
      for B19. However, it could not be determined when these children had been
      infected, and thus, a connection to TEC cannot be proved or excluded. No child
      showed B19 or HHV-6 DNA in serum or bone marrow collected at presentation.
      Isolation of virus from bone marrow, stools, and aspirate from nasopharynx
      culture was negative in all children but one, who had rotavirus in stool.
      CONCLUSIONS: HHV-6, B19, EBV, and cytomegalovirus are not common causative agents
      of TEC. The authors found no proof of any single agent causing TEC.

PMID- 11972100
TI  - Recombinant human interferon alpha-2a therapy in children with chronic immune
      thrombocytopenic purpura.
AB  - BACKGROUND: In a prospective study, 11 children with chronic immune
      thrombocytopenic purpura between ages 3 and 18 years were treated with
      recombinant human interferon alpha 2a (rhIFN alpha-2a). PATIENTS AND METHODS: A
      dose of 3 x 10(6) U/m2 three times weekly for 4 to 5 weeks (one cycle) was
      administered. Patients were treated with one to four cycles of rhIFN alpha-2a,
      and the outcomes were measured initially and 18 to 30 months after the last
      cycle. RESULTS: Good therapeutic responses (defined as platelet count >100 x
      10(9)/L) lasting for 18 to 30 months from the last interferon cycle were achieved
      in 6 of the 11 (55%) patients, including one with a probable spontaneous
      remission. Fair responses (platelet count 31-60 x 10(9)/L) for 18 months were
      achieved in 3 of the 11 (27%) patients. Only two patients, each treated only with
      one interferon cycle, exhibited no response. Side effects of treatment included
      fever and a flu-like syndrome, which were usually present during the first 14
      days of therapy only. CONCLUSIONS: Interferon-alpha appears to be an effective
      therapeutic approach to children with chronic immune thrombocytopenic purpura,
      with the potential of sustained long-term remission. A randomized, placebo
      controlled study is needed to confirm its role in this population.

PMID- 11972101
TI  - Thrombopoietin in preterm infants: gestational age-dependent response.
AB  - PURPOSE: To investigate the factors affecting thrombopoietin (TPO) levels in
      preterm infants and to determine if TPO levels differ in infants born to mothers
      with preeclampsia and those infants with culture-proven sepsis. METHODS: Serial
      serum samples (N = 95) were obtained from 27 infants less than 33 weeks'
      gestation. Samples were analyzed for TPO using enzyme-linked immunosorbent assay.
      All samples had an accompanying complete blood count. Analysis of variance with
      post hoc analysis by least significant difference test, Mann-Whitney test, or
      chi2 was used to compare groups, as appropriate. Forward, stepwise linear
      regression was used to account for potential confounding variables. Data are
      expressed as mean +/- SD. RESULTS: TPO levels were not significantly correlated
      with the absolute platelet counts (R = -0.04, P = 0.69). TPO levels were
      significantly correlated with gestational age (R= 0.50, P < 0.001) when the
      platelet count was less than 150,000/mm3. TPO levels were significantly elevated
      in infants with platelets less than 150,000/mm3 born to mothers with preeclampsia
      compared with infants with sepsis (1184 +/- 98 vs. 579 +/- 363 pg/mL, P < 0.01).
      After adjusting for confounding variables using multivariate analysis (model: r2
      = 0.43, P < 0.01), gestational age (r2 = 0.26) and preeclampsia (r2 = 0.03)
      remained significantly associated with TPO levels, whereas sepsis did not
      contribute to the variability of TPO. CONCLUSIONS: TPO response of infants with
      platelets less than 150,000/mm3 is dependent on gestational age. Infants with
      thrombocytopenia associated with preeclampsia have increased circulating levels
      of TPO. Infants with thrombocytopenia secondary to sepsis do not show an increase
      in TPO, but this appears to be an effect of low gestational age.

PMID- 11972103
TI  - Vertebral compression and eosinophilia in a child with acute lymphatic leukemia.
AB  - A 10-year-old girl, presenting with fever, eosinophilia, and back pain, was
      diagnosed with pre-B CD10-positive acute lymphoblastic leukemia. Eosinophilia
      resolved rapidly during remission induction treatment, but diffuse spinal
      osteopenia with multiple compression fractures became manifest after 4 weeks.
      During subsequent treatment the spine remineralized slowly, and after 26 months
      vertebral bone regeneration was apparent. Eosinophilia and osteopenia are
      separately known as early manifestations of acute lymphoblastic leukemia, but
      their simultaneous occurrence is particularly interesting. A late bone marrow
      relapse was not accompanied by bone changes or eosinophilia.

PMID- 11972102
TI  - Burkitt lymphoma associated with large gastric folds, pancreatic involvement, and
      biliary tract obstruction.
AB  - Large gastric folds in adults are seen in many benign and malignant conditions,
      but they are rare in children with malignant diseases such as non-Hodgkin
      lymphoma. The authors report a patient with non-Hodgkin lymphoma who had large
      gastric folds and jaundice as the initial symptoms. A 14-year-old boy was
      referred to the authors' hospital with upper abdominal pain and jaundice. A
      standard barium upper gastrointestinal series showed large gastric folds in the
      entire stomach. Magnetic resonance imaging showed a typical diffuse infiltrating
      type of pancreatic lymphoma. Because complete bilateral lower limb paralysis
      developed as a result of the epidural soft tissue mass, laminectomy and tumor
      resection were performed and a diagnosis of disseminated Burkitt lymphoma was
      established. After completing 6 months of chemotherapy, the patient has been
      disease-free without neurologic complications for 2.5 years.

PMID- 11972104
TI  - Congenital extrarenal non-central nervous system malignant rhabdoid tumor.
AB  - Malignant rhabdoid tumor (MRT) is a rare tumor occurring mostly in kidneys and
      central nervous system (CNS). Its prognosis is not good. Occasionally, MRTs are
      diagnosed at or immediately after birth. A female neonate presented with MRT in
      the chest wall, axilla, right elbow, and bone marrow. Chest wall lesion was
      resected completely. Although the masses in axilla and bone marrow responded
      rapidly to chemotherapy, the elbow lesion increased in size. Despite intense
      treatment, the tumor relapsed in lungs and the patient died 12 months after
      diagnosis. Review of the literature showed twenty additional congenital MRTs
      arising from sites outside of the kidney and central nervous system were
      published in the literature. Eighteen patients had disseminated disease at
      diagnosis. The median overall survival time for all (n = 21) patients was 2.0
      months (0-24 months). The only patient who survived had a localized tumor at
      initial diagnosis. Congenital, extrarenal, non-CNS MRTs are aggressive tumors
      with poor outcome.

PMID- 11972105
TI  - Interaction between methotrexate and ciprofloxacin.
AB  - High-dose methotrexate is used in malignant hemopathies and solid tumors in
      children. Methotrexate serum concentrations must be monitored because of the
      possible toxicity of drug elimination delay. Several drugs (e.g., penicillin,
      probenecid) can alter the elimination of methotrexate. The authors report two
      cases of delayed elimination of methotrexate in patients receiving ciprofloxacin,
      with severe toxicity.

PMID- 11972106
TI  - Treatment of severe thrombocytopenia with IL-11 in children with Wiskott-Aldrich
      syndrome.
AB  - This report examines the safety and efficacy of IL-11 in treating severe
      thrombocytopenia secondary to Wiskott-Aldrich syndrome in two pediatric patients
      before allogeneic stem cell transplantation (SCT). Both patients had a
      substantial increase in their platelet counts and a decrease in bleeding episodes
      and platelet transfusions. The median platelet count increased from 32,000/mm3 to
      64,000/mm3. Each subsequently received allogeneic SCT; 1 year after
      transplantation, both are reconstituted with 100% donor hematopoietic stem cells
      with sustained normal platelet counts (>200 K/mm3). Larger studies are required
      to confirm this observation of the safety and efficacy of IL-11 in this setting.

PMID- 11972107
TI  - Cobalamin C disease presenting as hemolytic-uremic syndrome in the neonatal
      period.
AB  - Anew case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS)
      in the neonatal period is described. A 28-day-old boy presented with failure to
      thrive, hypotonia, pancytopenia, and features of HUS (microangiopathic hemolytic
      anemia, thrombocytopenia, and renal failure). The possibility of the diagnosis of
      an underlying vitamin B12 disorder was prompted by evidence of megaloblastic
      changes on the peripheral smear and by finding in the literature a suggested
      association of neonatal HUS with this cobalamin-related metabolic disorder. Amino
      acid analysis showed elevated homocysteine levels in the plasma and increased
      levels of both homocysteine and methyl malonic acid in the urine. Diagnosis of
      cobalamin C disease was confirmed by complementation studies using skin
      fibroblasts. Therapy included parenteral hydroxocobalamin, carnitine, and
      leucovorin calcium (folinic acid). Cobalamin C disease should be considered in
      the diagnosis of patients presenting with HUS in infancy who have unexplained
      megaloblastosis, pancytopenia, neurologic impairment, and failure to thrive.
      Early diagnosis and institution of therapy may be effective in improving survival
      and quality of life.

PMID- 11972108
TI  - Effective control of infection-associated hemophagocytic syndrome with
      chloroquine.
AB  - A retrospective study was carried out to evaluate the efficacy and the side
      effects of chloroquine in the treatment of 27 patients with infection-associated
      hemophagocytic syndrome and compared these with patients described in the
      literature. All patients received 20 to 25 mg/kg chloroquine per day orally for 7
      days (a single course). Twenty-one patients who received one or two courses of
      treatment showed excellent responses; two patients showed no response to
      treatment. Two other patients refused to receive treatment with chloroquine. The
      response rate was 85.2%. Side effects were minimal and well tolerated. No
      relapses occurred in 19 patients. These results suggest that effective control of
      disease in some patients with infection-associated hemophagocytic syndrome can be
      achieved with chloroquine.

PMID- 11972109
TI  - Nurse prescribing empowers the new NHS.

PMID- 11972110
TI  - How the district nurse cares for the terminally ill patient with cachexia.
AB  - The aims of this study were to establish how district nurses cared for terminally
      ill patients with cachexia at home; to establish the priorities in the care
      given; and to establish the nurses' understanding of the core activities
      undertaken. The study allowed the views of district nurses to be examined in the
      context of their understanding of the care they gave. A literature review
      revealed that the metabolic disorders associated with cachexia mean that the
      condition is not simply the result of insufficient food intake. However, data
      from the study suggest that some district nurses have little understanding of the
      metabolic disorders associated with cachexia and revealed that care centres
      around advising and encouraging the cachectic patient to increase his/her food
      intake; such advice and encouragement were seen as the core activities in caring
      for the cachectic patient at home. This small study of 10 district nurse suggests
      that cachectic patients are put under unnecessary pressure to eat by both the
      formal and informal carer, and that as a result the patient may feel unsupported
      by the carers' lack of knowledge about his/her condition.

PMID- 11972111
TI  - Promoting planned care for patients with indwelling catheters.
AB  - Indwelling urinary catheters are common among patients in the community. Use of a
      catheter entails a significant lifestyle adjustment on the part of the patient,
      who must learn a new regime of self-care. In order to help patients to cope with
      the new device, it is essential that nurses play an active role in educating
      patients and involving them in the decision-making process. By empowering
      patients through knowledge of their condition and care, nurses can encourage
      greater compliance with care plans and reduce the risk of potentially distressing
      complications that can arise from indwelling catheters.

PMID- 11972112
TI  - An audit into homeless families in temporary accommodation.
AB  - This article describes a clinical audit project undertaken in a number of hostels
      providing temporary housing for homeless families and individuals in Hinckley,
      Leicestershire. The audit, carried out over a 6-week period, aimed to collect
      information about the health and social needs of the residents in the hostels to
      determine whether an on-site dedicated health visiting service would be of any
      benefit to them. Family members housed in three council-run hostels were
      interviewed and a detailed questionnaire was completed. This was used to gather
      information about the facilities in the hostels, the nutritional and mental
      status and health and social needs of the residents, the uptake of childhood
      immunizations and child health surveillance. It also provided information about
      the resident families' contact with their family health visitor. Families were
      living in cramped conditions with shared facilities and no safe play areas for
      their children. The audit clearly demonstrated that the residents living in the
      hostels had a range of health problems similar to those described in the
      literature about the homeless. As a result of the audit, a number of
      recommendations were made which are discussed in this article.

PMID- 11972114
TI  - Nurse prescribing in practice: patient choice in stoma care.
AB  - In the first of a new series, Janice Lee examines the choices facing nurse
      prescribers when selecting items for stoma management. Studies have estimated
      that there are up to 100,000 people with a stoma in England and Wales, and stoma
      care therefore forms a significant part of community nursing caseloads. The
      enormous range of available items means that both patient and prescriber are
      likely to have difficulty selecting the correct device. Patient preferences,
      comfort and pricing all play a part in stoma appliance selection.

PMID- 11972113
TI  - Family support by lay workers: a health visiting initiative.
AB  - There has been considerable research on the effectiveness of intensive
      professional home visiting schemes in improving parenting; lay visiting schemes,
      however, although often popular with clients, are under-researched. This article
      focuses on a lay visiting scheme set up and supported by health visitors in a
      deprived inner city area of Sheffield between 1998 and 2000. Although this scheme
      was designed to run for 2 years, an interim evaluation has taken place to track
      its effectiveness. This mainly qualitative evaluation has not only shown benefits
      to clients but also identified a number of issues for safe practice. The scheme
      has now been awarded core funding. It illuminates the kind of relationships that
      can develop between lay workers and clients, and enables a discussion of the
      benefits of this project and the challenge such schemes can present to both
      policy and practice.

PMID- 11972115
TI  - Facing the challenge of practice development in community nursing.
AB  - The large number of job titles associated with practice development within
      nursing can cause confusion as to the exact role of the person working within the
      development sphere. However, there is a recognized need for these development
      roles in the absence of clinical managerial positions and within the climate of
      continuing changes in the NHS. This article explores the skills required for
      practice development and is, in part, a reflective account of the work achieved
      over a 2-year period. The authors argue for clarity of purpose and continuing
      commitment from within the organization in order for these roles to achieve some
      degree of recognition, with specific reference to a community health care
      setting.

PMID- 11972116
TI  - The challenge of The NHS Plan: impossible mission?

PMID- 11972117
TI  - Senior nurses should reduce management role.

PMID- 11972118
TI  - Relationship-centred care is the next logical step.

PMID- 11972119
TI  - Psychiatric nurse who physically manhandled a vulnerable patient.

PMID- 11972120
TI  - Troubleshooting common problems associated with long-term catheters.
AB  - A catheter complications survey study, carried out over a 2-year period in three
      Bristol health districts, recorded 506 emergency referrals during a 6-month
      period (Kohler-Ockmore and Feneley, 1996). A further detailed study on 54 of the
      patients showed that 48% experienced catheter blockage and 37% reported urine
      bypassing. Urinary catheterization can cause many health problems; bacteriuria is
      inevitable in long-term catheterized patients (Cravens and Zweig, 2000). This
      article identifies some of the common problems that can occur with long-term
      catheters, makes recommendations and applies an evidence-based approach to
      catheter care. In order to identify and treat the associated problems, it is
      necessary to understand the anatomy and functions of the bladder. The article
      addresses this before examining the problems, which include: catheter blockage;
      bypassing of urine; catheter rejection and balloon non-deflation; and latex
      allergy. The psychological and social aspects, although not covered in this
      article, are also important and should always be considered along with all other
      aspects of care.

PMID- 11972121
TI  - Postoperative nausea management and patient-controlled analgesia.
AB  - Following the establishment of an acute pain service in one UK acute NHS trust,
      including the introduction of patient-controlled analgesia (PCA), pain scoring,
      and a rationalization of the use of simple analgesics, attention was drawn to an
      apparent increase in postoperative nausea and vomiting (PONV) among women given
      PCA following abdominal hysterectomy. Audits were conducted into clinical
      practice and patient satisfaction and it was agreed that an evaluation of the
      evidence should be conducted to ensure that the correct direction for development
      in the management of PONV could be established. This article discusses the
      evidence surrounding the issues regarding the management of PONV in patients who
      have been given PCA. The possibility of adding antiemetics to the analgesic
      solution, and the choice of antiemetic drugs, are investigated. Other factors
      that can affect the incidence of PONV in patients with PCA are also discussed,
      and an auditable framework for the evaluation of clinically effective practice is
      suggested.

PMID- 11972122
TI  - Review of home paediatric parenteral nutrition on the UK.
AB  - Home parenteral nutrition (HPN) is an expensive technological development which
      has given life to children with chronic intestinal failure. However, HPN is a
      complex therapy which carries life-threatening risks. The British Artificial
      Nutrition Survey (BANS), launched in 1996, monitors and audits HPN in the UK. It
      is the largest ongoing survey in the world, reviewing patients receiving enteral
      and parenteral nutrition. Data collated from health professionals between June
      1996 and September 1999 identified 81 children who were registered. The commonest
      diagnosis for starting HPN was short-bowel syndrome, with 41% of the children
      being under the age of 1 year. Readmission rates of children to hospital were
      reported as less than 2%, suggesting that most of the burden of care is placed on
      families. Questionnaire data received from families (response rate 38%)
      identified that sleep disturbance was common. Families also experience a
      deterioration in their family life. This relates to poor social life activities
      and overall quality of life after the child had started HPN. Further qualitative
      research data are required to review the ongoing psychosocial issues for
      families.

PMID- 11972123
TI  - Pressure area care in infants and children: Nimbus Paediatric System.
AB  - Survival rates in both critically and chronically ill infants and children have
      improved dramatically in recent years and new challenges exist in the nursing
      care given to these patients. Among these is the increased risk of pressure ulcer
      development. Children in intensive care environments are especially at risk.
      Prevention and management of pressure ulceration in the paediatric population
      requires clinical judgement and skill. The use of pressure ulcer risk assessment
      tools can assist in this process; however, to date, there is a lack of research
      evidence and further studies are needed. The pressure relief requirements of the
      paediatric patient are significantly different to those of the adult patient. In
      children under the age of 36 months, the ears and occiput are the areas most at
      risk of pressure injury as a result of the fact that this area is proportionately
      the largest and heaviest bony prominence. Despite the abundance of specialist
      pressure redistributing devices for adults, there is little available
      specifically for the paediatric patient. This article describes a review of the
      literature on these subject areas and follows with a short report of the
      evaluation of the new Paediatric Nimbus System undertaken at the Royal Hospital
      for Sick Children in Edinburgh.

PMID- 11972124
TI  - Legal aspects of consent 8: children under the age of 16 years.
AB  - Case Scenario: Mrs Gillick questioned the lawfulness of the Department of Health
      and Social Security (DHSS) circular HN[80]46 which was a revised version of part
      of a comprehensive memorandum of guidance on family planning services issued to
      health authorities in May 1974 under cover of circular HSC(IS)32. The circular
      stated that in certain circumstances a doctor could lawfully prescribe
      contraception for a girl under 16 without the consent of the parents. Mrs Gillick
      wrote to the acting administrator formally forbidding any medical staff employed
      by the Norfolk Area Health Authority (AHA) to give 'any contraceptive or abortion
      advice or treatment whatever to my daughters whilst they are under 16 years
      without my consent.' The administrator replied that the treatment prescribed by a
      doctor is a matter for the doctor's clinical judgement, taking into account all
      the factors of the case. Mrs Gillick, who had five daughters, brought an action
      against the AHA and the DHSS seeking a declaration that the notice gave advice
      which was unlawful and wrong and which did or might adversely affect the welfare
      of her children, her right as a parent and her ability to discharge properly her
      duties as a parent. She sought a declaration that no doctor or other professional
      person employed by the health authority might give any contraceptive or abortion
      advice or treatment to any of her children below the age of 16 without her
      previous knowledge and consent. SOURCE: Gillick v. West Norfolk and Wisbech AHA
      and the DHSS [1985].

PMID- 11972125
TI  - Back pain management: a patient satisfaction study of services.
AB  - The objectives of this study were to assess patient satisfaction with the current
      services provided for back pain, and to increase the level of understanding from
      the patients' perspective on beliefs about their back pain and how it affects
      their daily life. The study was conducted in two parts combining both
      quantitative and qualitative methodology. The main findings in the study revealed
      a high level of satisfaction with the services provided by the physiotherapy
      department and mixed levels of satisfaction with the GP. The GP was seen to be an
      expert yet failed to exhibit up-to-date knowledge about the causes and treatments
      for back pain. The issue of locus of control was a dominant theme throughout the
      study and those with stronger internal beliefs had a more positive outlook. The
      study revealed gaps in the current service provided, and the need for a more
      easily accessed service was desired.

PMID- 11972126
TI  - The Tielle family of dressings: overview of the product range.
AB  - The Tielle family (Johnson & Johnson Medical) is a range of dressings that come
      in a variety of shapes and sizes, designed to fit the different types and
      locations of wounds that occur in practice. There are three types--Tielle, Tielle
      Lite and Tielle Plus--and the choice of dressing should be based on the degree of
      exudate that the wound is producing. This product focus aims to give an overview
      of the range and provides research-based evidence for application in clinical
      practice.

PMID- 11972128
TI  - It is possible to recognize higher level nurses.

PMID- 11972127
TI  - Use of Exu-Dry in the management of a variety of exuding wounds.
AB  - Exu-Dry is a relatively new product that is designed to manage a variety of
      exuding wounds. It is a one-piece, multilayer, highly absorbent, non-adherent
      wound dressing. It is unique in construction, and incorporates a non-adherent
      wound contact layer which, it is suggested, makes dressing changes less painful
      and traumatic. This article explores the use of Exu-Dry in wounds, including
      heavily exuding wounds, burns, pressure ulcers, skin grafts, donor sites and
      fungating wounds.

PMID- 11972136
TI  - [Executive functioning in unipolar depression: a review].
AB  - While several neuropsychological studies have demonstrated that cognitive
      deficits are seen across a broad range of cognitive domains, executive deficits
      associated with frontal lobe dysfunction may be prominent in depression.
      Executive function refers to cognitive processes that control and integrate other
      cognitive activities such as episodic memory. These executive functions involve a
      set of cognitive behaviors which include: dealing with novelty, selecting
      strategies, inhibiting incorrect responses, monitoring performance and using
      feedback to adjust future responding. The measurement of executive function
      relies mainly on the use of neuropsychological tests known to be sensitive to
      frontal lobe damage such as the Wisconsin and California Card Sorting Tests,
      verbal fluency tests, Stroop-test, Tower of London Task and Trail Making Test.
      The present review focuses on studies investigating executive functions in
      primary unipolar depression with these neuropsychological tasks. Unipolar
      depressed patients mainly exhibit cognitive inhibition deficits, problem-solving
      impairments and planning deficits. Cognitive inhibition deficits in depressed
      patients have been related to a reduction of cognitive resources and psychomotor
      retardation. Inhibition disturbance could lead depressed patients to process
      irrelevant information and consequently reduce their capacity to control
      transient mood changes. Several studies have found evidence of problem solving
      impairments in depressed patients. Depressed subjects show with card sorting
      tests difficulties in hypothesis testing with a loss of spontaneous and reactive
      cognitive flexibility. The cognitive rigidity and hypothesis-testing associated
      with dorsolateral prefrontal dysfunction in depression may prevent patients to
      cope with life events and lead to a perpetuation of depressed mood by a
      continuation of stress exposure. Planning tasks, such as the Tower of London
      Test, also demonstrate that depressed patients fail to use negative feedback as a
      motivational boost to improve their performance. Both trait and state factors
      influence the executive level of depressed patients. Executive deficits have been
      reported in more severely depressed subjects with melancholic or psychotic
      features. Executive functioning also might predict a poorer outcome in
      depression. Thus initiation and perseveration scores - a measure of cognitive
      flexibility - is associated with relapse and recurrence of depression and
      residual depressive symptoms. Brain imaging studies show that reduced blood flow,
      particularly in medial prefrontal cortex and dorsal anterior cingulate cortex
      subserve executive impairments in depression. However neuroimaging studies
      underscore the importance of mood-cognitive interactions in depression. A recent
      working model of depression (Mayberg et al., 1999) implicates failure of the
      coordinated interactions of distributed cortical-limbic pathways in the
      neuropsychopathology of depression. According to this model, neocortical
      (prefrontal and parietal regions) and superior limbic elements (dorsal anterior
      cingulate) are postulated to mediate impaired attention and executive function,
      whereas ventral limbic regions (ventral anterior cingulate, subcortical
      structures) are postulated to mediate circadian and vegetative aspects of
      depression. Further studies are needed to validate this model at the
      neuropsychological level as well as the brain level and to elucidate the complex
      interactions between mood, cognitive resources and executive function in
      depression.

PMID- 11972137
TI  - [Formal thought disorders: French translation of the Thought, Language and
      Communication assessment scale].
AB  - This article proposes a french translation of Andreasen's Thought, Language and
      Communication (TLC) scale (Andreasen, 1979). This scale is widely used in current
      literature and remains a reference due to the fact that it has made it possible
      to establish a consensus with regard to formal thought disorders and has
      contributed to the operationalisation of the concept of dissociation. This scale
      consists of 18 items. Each item is clearly defined through the use of clinical
      examples, rated from 0 to 4 as a function of the intensity of the disorder
      (absent, slight, medium, severe, extreme). The interview conditions are also
      stated: free interview of minimum 10 minutes followed by a more structured
      interview. Some items of the TLC are taken directly from the SANS and SAPS. Their
      translation has been taken over from french translations already validated by
      Lecrubier and Boyer (1987). The others were translated within the department and
      have been verified by a native English speaker. The entirely of the translation
      has been verified by Andreasen. The metrological qualities of this french
      translation have been studied in a population of 107 schizophrenic patients who
      fulfilled all the DSM IV criteria: 73 males and 34 females, mean age 33.4 9
      years, in or outpatients, all under neuroleptic treatment and all evaluated by an
      experienced clinician. Thirty one patients have been filmed to assess the
      interjudge reliability. The results indicate a high level of interjudge
      consistency (interclass correlation coefficient 0.96). The global score was 17
      9.4. In the factorial analysis before rotation we observe a main factor that
      makes it possible to calculate a global score. The results of factor analysis of
      the TLC variables after rotation yield five factors that have an eigen value
      greater than 1. These five factors explain 66% of the variance. All items have a
      weight greater than 0.45. The first factor includes Poverty of content speech,
      Tangentiality, Derailment, Incoherence, Illogical thinking, Loss of goal and
      Perseveration. It reflects thinking disorganisation. The second factor includes
      Pressure of speech, Circumstantiality, Self reference and Poverty of speech
      (negative weight). This factor reflects verbal production. The third factor is
      composed of Clanging, Neologisms, Word approximation and Echolalia. This factor
      reflects verbal structure. The fourth factor is only composed of Stilted speech
      and the fifth one composed of Distractible speech and Blocking. These data have
      been compared to those reported in the literature: Andreasen in 1979 (113
      patients: 32 suffering from manic disorder, 36 from depressive disorder and 45
      schizophrenic disorder) and in 1986 (194 subjects: 94 controls, 25 suffering from
      manic disorder, 25 schizoaffective disorder and 50 schizophrenic patients),
      Harvey in 1992 (115 schizophrenic patients) and Peralta in 1992 (142
      schizophrenic patients). Response levels for each item of the TLC french
      translation were very close to those found in the english versions. Differences
      in scores can be explained by clinical differences between populations studied.
      Factorial analyses also correspond well to such versions. In particular, after
      rotation, the three factorial subscores found representative of disorganisation,
      verbal production and verbal structure respectively are closed to those proposed
      by the english versions. In conclusion, the translation of Andreasen's Thought,
      Language and Communication (TLC) scale (Andreasen 1979) that we propose here
      therefore appears to exhibit metrological qualities sufficiently close to those
      reported in literature to permit its generalised use in France.

PMID- 11972138
TI  - [French translation and validation of the Tension-Effort Stress Inventory (TESI,
      7) emotional list].
AB  - Since emotion became a central topic in scientific psychology, a conceptual
      consensus is needed with regard to its definition. Reversal theory provides such
      a widely, comprehensive theory of emotion that is currently missing from the
      psychology literature. According to reversal theorists, there are 16 primary
      emotions corresponding directly to one's preferred and non preferred
      phenomenological experiences. These include 4 pleasant/somatic emotions
      (relaxation, excitement, placidity, provocativeness), 4 unpleasant/somatic
      emotions (anxiety, anger, boredom, sullenness), 4 pleasant/transactional emotions
      (pride, modesty, gratitude, virtue) and 4 unpleasant/transactional emotions
      (humiliation, resentment, shame and guilt). Tension-Effort Stress Inventory
      (TESI, is an auto questionnaire with the 3rd section containing this 16 primary
      emotions list. The aim of our study deals with french translation and factorial
      validation of this list. Method and procedure - Participants (n=46) were
      voluntary french speaking individuals who prepared to be involved in a new
      tourist attraction established in a french winter sport resort. This attraction
      is made up of a 950 meters-long carrying cable tightened to an altitude of 100
      meters above the ground, offering anyone whose weight exceeds 40 kg a thrilling
      90 km/h rush. Of the sample of 46 individuals, 29 were male and 17 were female.
      The average age was 31,4 years with a 18-59 range and 7,7 as standard deviation
      value. Each subject had to complete a french version of TESI just before being
      hang on the cable and just after his or her arrival on the landing zone. Results 
      Pre- and post-activity descriptive statistics for each item were subjected to
      Pearson correlations calculation and then, an explanatory factorial analysis was
      carried out. Principal component analysis results (after varimax rotation)
      exhibited 6 factors explaining a proportion of 64% of the total variance: 4 of
      these 6 dimensions seemed to be similar to the ones claimed by reversal theory; 1
      dimension resembled a more popular conception of emotion experience which is  bad
      mood ; 1 composite dimension was more ambiguous (anxiety + modesty). Confirmatory
      factorial analysis (carried out from variance/covariance matrix) proved to be
      conclusive in assessing the fit of the data with regard to reversal theory
      classification of emotions. Thus, the eight pleasant emotions were found to be
      dichotomised into four somatic and four transactional emotions with satisfactory
      fit indexes [GFI (Goodness of Fit Index)=0,92, residuals=0,09]. In addition, the
      eight unpleasant emotions were also split up into 4 somatic and 4 transactional
      groupings with comparable ratings (GFI=0,93, residuals=0,07). Conclusion - This
      french version of TESI emotional list appears to be suitable in assessing one's
      phenomenological emotional experiences. The equipartition according to
      pleasant/unpleasant and somatic/transactional dimensions meets the original
      classification postulated by reversal theorists.

PMID- 11972139
TI  - [Pharmaco-epidemiological study on antipsychotic drug prescription in French
      Psychiatry: Patient characteristics, antipsychotic treatment, and care management
      for schizophrenia].
AB  - In 2000, a one week national survey was conducted among 202 psychiatrists (129
      participants) in France, from hospitals and clinics, private or public. The first
      20 inpatients and 10 outpatients prescribed at least one antipsychotic drug (age
      range 18-65), were included. The diagnostic procedure was standardized with a
      structured interview: the Mini International Neuropsychiatric Interview (MINI). A
      total 2 068 patients were included, among whom 892 (43.1%) reached the criteria
      of schizophrenia according ICD-10. We present here data on these latter patients.
      Mean age was 38.8 years; with 38.8% females. Median duration of current
      antipsychotic treatment was 0.5 year in inpatients and 2 years in outpatients.
      Median duration of any antipsychotic treatment was 10 years, without difference
      between groups. Comorbid situations (anxiety disorder, depression and suicidal
      risk) were found in 33.1% of schizophrenic patients, with higher frequency among
      inpatients in private hospitals (54.8%) than in other groups. 46.8% patients were
      prescribed at least 2 neuroleptics, and 73.6% at least one non-neuroleptic drugs.
      Cyamemazine accounted for 16.6% of all neuroleptics drugs, and 56% of patients
      were prescribed an atypical antipsychotic (risperidone, olanzapine, amisulpride
      or clozapine). Atypical drugs accounted for 59.4% of patients who were prescribed
      only one neuroleptic drug. Inpatients had more neuroleptics coprescription than
      outpatients (mean 1.8 vs 1.4 drugs), with higher daily dose. In addition,
      inpatients had more other psychotropics prescribed (mean 1.5 vs 1.1 drugs).
      Overall, more other psychotropic drugs were prescribed among patients with -,
      than those without - comorbid situations (1.7 vs 1.2 drugs). Median time since
      admission, at the time of the study, were similar in private and public hospitals
      (107 vs 99 days) but maximal time since admission was respectively 2.8 and 48.9
      years. Visit frequency for outpatients was more than one every two weeks for
      43.1% in private and 24.7% in public clinics. Among inpatients only we found a
      difference between private and public hospitals for polypharmacy of non
      neuroleptics psychotropics, (mean 1.9 vs 1.5). In outpatients, long acting depot
      accounted for 26.6% of neuroleptics treatments in public clinics and 15.4% in
      private clinics. Finally, we found that polypharmacy among outpatients increased
      with duration of antipsychotic treatment. CONCLUSION: in France, important
      differences are reported in antipsychotic prescription for schizophrenia between
      in- and outpatients. Current antipsychotic prescription is more recent in
      inpatients than in outpatients, with similar duration of overall antipsychotic
      treatment. Inpatients have more drug prescription, antipsychotics and other
      psychotropics, than outpatients. Differences are less important between private
      and public providers. Inpatients in private hospitals receive more non
      neuroleptic drugs than in public hospitals, and depot antipsychotics are more
      used among patients of public clinics. Long term inpatients are found in public
      hospitals only. Outpatients follow up is more intensive in private than in public
      clinics.

PMID- 11972140
TI  - [Study of the stress response: role of anxiety, cortisol and DHEAs].
AB  - AIM OF THE STUDY: Several studies have exhibited the psychological processes that
      are implied in the stress response and have shown, according to Selye's research,
      the participation of the hypothalamic-pituitary-adrenal axis and the major role
      of cortisol. The possible action of another adrenal steroid,
      dehydroepiandrosterone (DHEA), is increasingly documented. The beneficial effect
      of the latter and his antistress role would be related to an antagonistic action
      to that of cortisol. The aim of our study was, first to assess biological and
      psychological aspects of the stress response, then to define the relationships
      that exist between these two processes. POPULATION AND METHODOLOGY: 40 subjects
      (21 women) aged 42 +/- 12 years, who consulted within a clinic of stress (CITES
      Prevert, Liege, Belgium) were studied. They all felt stressed but, according to
      DSM IV, were without mental disorders and drug free when examined. Subjects were
      asked to accomplish simple cognitive tasks: 1 - to distinguish two different
      auditory stimulations. The first one was a high-pitched sound of 1 470 Hz, which
      was presented unfrequently (20%). The second one, a low frequency tone of 800 Hz,
      was presented more frequently (80%). The interval between both stimuli was 1 s.
      The subject had to press a button when the rare stimulus was recognized. 2 - to
      extinguish a light after a warning tone of 64 dB, 50 ms and 1 000 Hz. The light,
      which followed one second later the tone, consisted of a series of flashes of 18
      c/s that the subject had to stop by pressing a button. The purpose of this second
      procedure was that the subject was warned and had to prepare and anticipate the
      most rapid response. After that, subjects were submitted to self-evaluation
      psychological tests. The impact of psychosocial factors was assessed by Amiel
      Lebigre life events questionnaire. Personality features and emotional response
      (state anxiety, related to experimental situation) were assessed by Spielberger
      inventory (STAI: State and Trait Anxiety Inventory). Psychological tests are
      practised immediately after experimental situation. Cortisol and DHEAs
      (dehydroepiandrosterone sulfate) were measured in blood samples taken before (t1)
      and after (t2) the experimental test. Cortisol was measured by radio-immunology
      and expressed as ng/ml of plasma. DHEAs was measured by radio-immunoassay and
      expressed as g/liter of plasma. RESULTS AND DISCUSSION: The majority of subjects
      displayed high scores of trait anxiety (37 subjects had a score>42) and life
      events impact (35 subjects had a score>200). These data confirmed that the
      subjects were fragile and were obviously stressed. In response to the cognitive
      tasks, that constituted for each subject a new event with which it was necessary
      to cope, 25 subjects exhibited high level of state anxiety (score>42) and an
      increase of cortisol plasmatic concentrations occurred solely in 11 persons. Ten
      among them were in the group of subjects which displayed a score of state
      anxiety>42 (p=0,0223, Chi square). Base on these data three types of stress
      response were identified: 1 - the experimental situation was experienced without
      anxiety ( psychological silence ) and without any increase in cortisol level (
      biological silence ). There was no stress and these subjects were, despite their
      vulnerability, close to a normal health state . 2 - high emotional reaction (high
      level of state anxiety) was observed. This response reveals a psychological
      vulnerability that can be considered as the expression of a consecutive
      psychological distress induced by a threatening experimental situation. There
      were no biological manifestations ( biological silence ). 3 - high state anxiety
      and increased plasma cortisol levels were observed. The corresponding subjects
      were obviously more vulnerable. CONCLUSION: These results allow us to propose
      that the emergence of state anxiety is the first stress response and the primary
      protest . Up to a certain level, a plateau level, anxiety remains stable. Then,
      nature of the stress response changes and takes a biological aspect. Increased of
      cortisol plasma levels, the secondary protest , is observed and gives evidence of
      an intensified and sustained stress response. Such a gradual phenomenon is
      particularly reported in elevated psychological distress which is associated with
      loss of control. It is important to note that identical scores of state anxiety
      (Mann Whitney test) were observed in anxious subjects with or without rise of
      plasma cortisol levels. DHEAs was also implied in the stress response. The
      enhancement of plasma levels of DHEAs were dependent on cortisol, as shown by the
      close correlation between both hormones (r=0,433, p=0,0033, Spearman test). The
      hypothesis of an antagonism between these two hormones is based on the fact that
      DHEAs opposes the action of cortisol and exerts a true anticortisol effect. This
      antagonism might be related to a competition in their synthesis and release by
      the adrenal gland. In the present case, high level of anxiety (state and trait)
      was associated with an increase of cortisol, while low level (of anxiety) was
      related to an exclusive rise of DHEAs. Intermediate anxious score was observed in
      subjects who showed increases of both cortisol and DHEAs (p=0,0225, Kruskall
      Wallis test). Furthermore, a close relationship (negative correlation: Spearman
      test), was observed between increases in DHEAS and scores of state anxiety (r=-
      0,382, p=0,06) and trait anxiety (r=- 0,0097, p=0,527). This means that the
      worriness and the underlying anxious ruminations and negative anticipations,
      which characterize trait anxiety, were less important in subjects who increased
      plasma DHEAs levels. In addition, emotional tension and uneasiness, which
      accompanies state anxiety, were also less marked. There are no studies reporting
      a relation between DHEA(s) and state or trait anxiety. Nevertheless, many authors
      have proposed a beneficial action of DHEA on the feeling of well-being. This
      beneficial role could be related to a double action of DHEA: a direct effect
      provided by its transformation into sexual hormones, an indirect one mediated by
      its competition with cortisol, of which the synthesis and consequently the
      activity decrease.

PMID- 11972141
TI  - [Do the glutamate excitotoxicity theory and potential free radicals implication
      in schizophrenia aetiopathogenesis provide a new enlightenment to links between:
      genome, environment and biology in the determinism of that disorder?].
AB  - The aetiopathogenesis of schizophrenia constitutes nowadays one of the major
      points of interest for researchers on this cosmopolitan disorder which involves
      about 1% of the world population and which significantly alters the social
      functioning of the individual. Numerous studies have focused on the role played
      by genome, environmental factors and biology in the development of symptoms. The
      neurodevelopmental theory is an illustration with the perinatal period considered
      as the main provider of environmental factors (hypertension, infections,
      bleedings during pregnancy, acute and chronic fetal distress.). Many authors
      found significant associations between such factors, the occurrence of brain
      lesions and finally schizophrenic symptoms. Although no convincing genetic model
      had been established to date for schizophrenia, nevertheless it appears that a
      predisposition not inheritable under the mendelian mode exists and authors showed
      that disease gets more and more severe over schizophrenic descendants. The risk
      to be schizophrenic being a first degree relative of the schizophrenic person is
      about ten time superior than in general population. Indeed, this risk is also
      about ten time superior in biological parents of schizophrenic adoptees than in
      biological parents of healthy adoptees. Studies done in monozygotic comparing to
      dizygotic twins are in favour of an important role played by genetic factors more
      than socioeducational or psychological factors. Concerning biology, the
      dopaminergic hypothesis remains shared by numerous authors although direct links
      with incriminated factors are not well established. Now is suspected the
      glutamate excitotoxicity with implication of free radicals in schizophrenia.
      These free radicals are products of various enzymatic activations led by
      overstimulation of post synaptic receptors (NMDA and AMPA) by the excess
      glutamate. Therefore, according to that concept, some amino acids as glutamate
      and derivatives could have through free radicals a noxious effect on neuronal
      synapses. This could be due to a failing of their recapture at the presynaptic
      level in addition to a dysfunctioning of the antioxidizing system (glutathion,
      carnosine, superoxide dismutase, aspartate) to which dopamine and other
      monoamines might participate. The question is whether or not this theory
      contributes to shed light on links between: genome, environmental factors and
      biology in schizophrenia. Through the review and discussion of genetical aspects
      of schizophrenia, environmental factors and the biological aspect, we intend to
      revive debate on that question. The articles and authors were selected with
      regard to the aptness of their publications on that subject, their evolving ideas
      and finally the interest of their works for neurosciences. This new approach
      perhaps is opening the way to new therapeutic perspectives in the treatment of
      schizophrenia based on the antioxidizing substances as shown for some
      neurological diseases (amyotrophic lateral sclerosis, Parkinson's disease and
      Huntington's chorea) for which experiments are going on.

PMID- 11972142
TI  - [Amnesic presentations of the compulsive obsessional confusions (about 3 patients
      appearing in a consultation of memory)].
AB  - Disorders or complaints of memory are a frequent cause of consultation in
      depression, major anxiety and psychiatry disease with personality disorders. We
      report 3 patients with obsessive compulsive disorder (OCD), without diagnosis and
      treatment, examined in a specialized memory consultation. They always had OCD
      with cognitive checking. Diagnosis of transient global amnesia and temporal
      complex seizure were discussed in 2 cases. Psychometric impairment only was
      observed in first free recall of a verbal memory task and was no specific.
      Behavioural during testing seemed to be very important to analyse. First, a 49
      year-old man consulted because he had stereotyped transient amnesia lasted one
      minute, 2 or 3 times a week, since 6 months. He was a teacher. Transient amnesia
      always occurred during lessons. Suddenly he didn't know where he was or what he
      was speaking about. Episodes lasted one minute. After them, he had no confusion
      and no difficulty in concentration but intense anxiety. In an another hand, when
      he was in his car, after lessons, he could forget where he was during some
      minutes. CT scan and EEG were normal. Neuropsychological tests only objectived
      impairment in first free recall of Grober and Buschke's words. Patient explained
      that he could not prevent to check responses. He told us checking obsessive
      compulsive disorder during since long time ago. We discussed clear differences
      which existed between seizure and ruminations or preoccupations. Secondly, a 55
      year-old woman was afraid of her memory performances. She was medical secretary
      and had no problem in her work but she would like a memory consultation to
      reassure herself. She was neither depressed nor anxious. She presented curious
      production in fluency task. She had to produce as many animals's names as
      possible: she could say 35 names which was an excellent performance but only in
      alphabetic order! Neuropsychological tests objectived impairment in her first
      free recall of Grober and Buschke's words. She tried in her first free recall to
      remember words in alphabetic order. She explained how she was bound to range
      everything in alphabetic order! She had a lot of rituals. She thought that she
      had an obsessive compulsive disorder but never consulted about this. The
      observation illustrated suspiscions about memory operations which could be
      observed in patients group with obsessive compulsive disorders. Finally, a 62
      year-old man told us that he had presented a transient global amnesia during 4
      hours. He had an important appointment and was upset about that. He didn't go to
      it and wandered in his flat. He always asked the same questions and forgot
      everything. He had no neurological deficit. He was anxious, sad and cried several
      times. He perfectly remembered the episod and thought that he had a panic attack!
      Verbal memory tests only objectived difficulties in his first free recall of
      Grober and Buschke words as the two others patients. He had a story of obsessive
      compulsive disorder with checking and rituals. In this observation, we discussed
      clear differences which existed between panic attacks and global transient
      amnesia. We analyzed patterns of neuropsychological performances which
      illustrated clinical features of obsessive compulsive disorder. These three
      patients impaired in their first free recall of verbal memory task. It is not a
      specific result. We observed during psychometric evaluation, strategic processing
      which impaired episodic memory: patients tried to check their performances.
      Memory complaints only were observed in checking obsessive compulsive disorder.
      It is a difficulty or a doubt about memory capacities. Difficulties could be due
      to particular cognitive processes who pertubate normal memory capacities.

PMID- 11972143
TI  - [Effect of comorbid substance use on neuropsychological performance in subjects
      with psychotic or mood disorders].
AB  - Objective - Patients presenting with psychotic or mood disorders present with
      neuropsychological deficits such as executive and memory disturbance. Deficits of
      these functions have also been reported in patients presenting with alcohol use
      or substance use disorders. A large percentage of patients with non-affective
      psychotic or mood disorders present with a comorbid substance use disorder. These
      subjects are often a priori excluded from most neuropsychological studies.
      However, using such an exclusion criterion may induce a selection bias linked to
      the high prevalence of this dual diagnosis. It is therefore necessary to further
      explore the impact of substance abuse on neuropsychological performance in
      subjects with psychotic or mood disorders. Method - Patients consecutively
      hospitalized for a non-affective psychotic disorder or a mood disorder were
      included. A standardised method was used to collect information on addictive
      behaviour, clinical and social characteristics. DSM IV diagnoses, including those
      of substance use, were made using a structured diagnostic interview and all other
      available clinical and historical information collected during the hospital stay.
      Memory performance was tested using the Batterie d'Efficience Mnesique 84
      (Battery of memory efficiency 84 items, BEM 84). Executive abilities were
      explored using the Wisconsin Card Sorting Test (WCST) and the Stroop test.
      ANCOVAs with cannabis use disorder or alcohol use disorder as main factor were
      used to examine associations with neuropsychological test scores. Results - We
      have included 77 patients fulfilling the diagnostic criteria for non-affective
      psychotic disorders (schizophrenia, schizoaffective disorder, delusional
      disorder, other psychotic disorder, n=35) or mood disorders (n=42). Among these
      patients, 27.3% presented with a lifetime history of alcohol abuse/dependence
      (current prevalence: 14.3%) and 23.4% presented with a lifetime history of
      cannabis abuse/dependence (current prevalence: 11.7%). We have assessed the
      specific impact of alcohol and cannabis use on neuropsychological performance. No
      significant differences on memory and executive performance were found between
      patients presenting with and without a lifetime history of alcohol
      abuse/dependence. These results were not modified after adjustement for potential
      confounding factors (age, gender, educational level, age at onset, diagnosis,
      current versus past addictive behaviour). Patients with a lifetime history of
      cannabis abuse/dependence had significantly higher (i.e. better performance)
      general BEM 84 score (F=3.89, df=1, p=0.05), higher complex figure delayed recall
      scores (F=6.62, df=1, p=0.01) and higher recognition scores (F=3.9, df=1, p=0.05)
      than patients presenting without a lifetime history of cannabis use. After
      adjustment on covariables (age, gender, educational level, age at onset,
      diagnosis, current versus past addictive behaviour), the differences on memory
      performance between the two groups were no longer significant, the differences
      found before adjustment were mainly explained by the confounding effect of age.
      Patients presenting with a lifetime history of cannabis abuse/dependence had
      significantly lower interference scores on the Stroop test than subjects without
      cannabis use (F=5.67, df=1, p=0.02). This finding was not modified after
      adjustment for confounding factors. Information on substance use was collected by
      interviewing the patient and was completed by using all other available source of
      information, but no urine testing was performed. Thus, substance use could have
      been underestimated or unrecognized in some patients. We did not distinguish
      patients who presented with substance abuse from those who presented with
      dependence because there were few of the latter. Distinguishing these two
      populations would be of interest because dependence may have a more deleterious
      effect than abuse in neuropsychological performances. Finally, we did not
      included normal control subjects so we can not assess if our cohort present with
      memory and executive deficits compared to normal subjects. Conclusion - Comorbid
      alcohol or cannabis abuse/dependence has limited effects on memory and executive
      abilities in subjects with psychotic or mood disorder. The only significant
      difference between subjects with and without a dual diagnosis was that subjects
      with cannabis use disorder performed poorly on the Stroop test. No other
      significant difference in executive and memory performance was found after
      adjustment for confounding factors. Since there is a high prevalence of a
      comorbid substance use disorder in subjects with psychotic or mood disorder, the
      exclusion of these patients in neuropsychological studies may not be
      systematically justified.

PMID- 11972145
TI  - [Surgery of intracranial epidermoid cysts. Report of 44 patients and review of
      the literature].
AB  - Forty-four patients (22 males and 22 females) were admitted to our institution
      for an intracranial epidermoid cyst between 1980 and 2000. Their mean age was
      39.9 years. The duration of the disease at admission varied between a few days
      and 30 years. CT-scan was performed in all cases, MRI in 33 cases with a
      diffusion sequence in 3. Most of the 26 patients with posterior fossa lesions
      were treated surgically in the sitting position, with resection of the tonsils in
      four cases in order to minimize cerebellar retraction. The other supratentorial
      tumors were operated using a fronto-temporo-pterional approach in 13 cases (with
      temporo-polar lobectomy in 6 cases), or a parietal transparenchymal approach in
      the parieto-occipital lesions (2 cases). The resection was total or subtotal
      (residual capsule) in 79.5% of cases. Post-operative morbidity was 13.6% and
      mortality 8.9%. The median follow-up was 8 years, with a recurrence rate of 4.5%.
      Epidermoid cysts are benign, slowly but ineluctably growing tumors which require
      surgical treatment. Their diagnosis has become easier, especially with the
      development of MRI diffusion sequences. Morbidity and mortality (morbi-mortality)
      reported in the literature as well as found in our series seems to be unrelated
      to classical aseptic meningitis (22.7% in our series) or hydrocephalus (2 cases
      in our series). For many authors, it may be the consequence of systematic
      resection of the tumor capsule. This does not seem to be the case in our series
      in which only 25% of the patients underwent a complete resection. Prolonged
      cerebral retraction could be one of the responsible factors. One of the technical
      proposals could be to perform a transparenchymal approach in selected patients.

PMID- 11972144
TI  - [Transcranial magnetic stimulation in depression].
AB  - Among the new therapeutic techniques in psychiatry, transcranial magnetic
      stimulation (TMS) seems to bring a profit in the treatment of depressions. It
      uses the principle of inductance to generate a magnetic current, which in turn
      activates cortical neurons. Stimulation is highly focused and interests specific
      regions of the cerebral cortex. This therapeutic technique is generally well
      tolerated. Side effects are rare, the most hampering one is epileptic seizures.
      It is favored by high frequencies (above 5 Hz) and arises mainly with patients
      having a history of personal or family epileptic seizures. The first open trials,
      quickly confirmed by controlled studies showed the efficiency of TMS in
      depression. With depression, double blind randomized trials, using high
      frequencies, stimulation of the left dorsolateral prefrontal cortex give positive
      results with significant decrease of scores on depressive scales applied to
      resistant and non resistant depressions. Some studies have stimulated the right
      dorsolateral prefrontal cortex using low frequencies. The decrease of scores is
      also significant on depressive scales. The modulating effect of rTMS on cortical
      excitability of the brain justifies this distinction between high and low
      frequencies, high frequencies having a facilitating effect whereas low
      frequencies have an inhibitory effect.

PMID- 11972146
TI  - [Pineal region surgery. Experience in 22 patients].
AB  - BACKGROUND AND PURPOSE: Different approaches to the pineal region are described
      in the literature with high mortality and morbidity. We report our experience
      with two different approaches (occipitoparietal or infratentorial supracerebellar
      approaches) for pineal region. METHODS: Between 1986 and 1997, 25 operations were
      performed in 22 patients. Preoperative work-up included a CT-scan with
      conventional angiography (for older patients), magnetic resonance imaging with
      angiographic study (angio-MRI) for the others. Two different approaches, the
      occipitoparietal (n=14) or the infratentorial supracerebellar (n=8) ones, were
      used. Three patients had a stereotactic biopsy, followed by a total resection for
      one of them. RESULTS: The mortality and morbidity induced by the approaches were
      low compared to the series of the literature. Only 2 patients were worsened by
      the surgery: Patient 4 developed hemianopsia after an occipitoparietal approach
      and patient 21 temporary Parinaud syndrome after resection of a teratoma by
      supracerebellar infratentorial approach. One patient improved his neurological
      status but died on the 10th postoperative day from pulmonary embolism.
      CONCLUSIONS: Total or partial resection of well-defined pineal region lesions by
      direct neurosurgical approaches can be achieved in most cases with low morbidity.
      The choice among the two surgical occipitoparietal or infratentorial
      supracerebellar approaches depends on the size and the location of the lesion in
      the pineal area, its relation to the ventricular system, the median line and the
      splenium. Angiographic sequences in magnetic resonance with study of the deep
      veins are helpful in this respect.

PMID- 11972147
TI  - [Ewing's sarcoma of the ethmoid bone. Case report].
AB  - Ewing's sarcoma is rarely located at the base of the skull. We report a case of
      ethmoid Ewing's sarcoma. Diagnosis was established on microscopic examination. A
      complete surgical resection was performed, followed by cranial base
      reconstruction. During the postoperative period, a combined course of
      chemotherapy and radiotherapy was performed. We also present a review of the
      literature.

PMID- 11972148
TI  - [Arterial aneurysm within a tumor in a pediatric patient].
AB  - A middle cerebral artery aneurysm, completely enclosed in a large frontotemporal
      anaplastic astrocytoma, is demonstrated in a 11-month-old girl admitted for
      intracranial hypertension. Clipping of the aneurysm along with radical resection
      was successfully performed. Five years later, follow-up neurological examination
      is normal, aneurysm occlusion and no evidence of tumor recurrence are
      demonstrated by angiogram and MRI. The association of brain tumor and aneurysm is
      discussed, and documented with the only two cases of a neoplasm surrounding on
      aneurysm reported in the literature.

PMID- 11972149
TI  - [Complete imaging study of internal carotid artery agenesis with intercavernous
      anastomosis].
AB  - We report a complete imaging study of an exceptional developmental anomaly of the
      internal carotid artery in a 42-year-old man presenting with a few days history
      of left visual blurring. MRI and conventional angiography demonstrated unilateral
      cervical and petrous agenesis of the left internal carotid artery, with an
      intercavernous anastomosis. CT-scan revealed total absence of the bony carotid
      canal. We briefly review the embryological hypotheses and discuss clues to
      correct diagnosis.

PMID- 11972150
TI  - [Metastatic and hemorrhagic brain arteriovenous fistulae due to a
      choriocarcinoma. Case report].
AB  - Brain metastasis of choriocarinoma is uncommon. These tumors develop in women of
      childbearing age and commonly produce signs and symptoms of subarachnoid
      hemorrhage, intracerebral hemorrhage, or brain tumor. Diagnosis can be
      established by histologic study of operative swabs and bioassay of the patient's
      blood, urine and cerebrospinal fluid for chorionic gonadotropin. This condition
      is highly chemo- and radiosensitive. We report the case of a 36-year-old woman
      with intracranial neoplastic fistulae. Rupture occurred 3 days after spontaneous
      abortion at 3 months of pregnancy. The patient presented with hemiplegia, aphasia
      and unclear consciousness. Left fronto-parietal hematoma was diagnosed on the CT
      scan, and cerebral angiography showed an arteriovenous intracranial fistulae. The
      hematoma and angioma were surgically removed successfully. The histological
      examination showed a metastatic choriocarcinoma. Surgery was followed by
      chemotherapy and radiotherapy. After 6 years of follow-up, complete remission has
      been obtained.

PMID- 11972151
TI  - [Spinal cord histoplasmoma. A case report].
AB  - Over a period of 2 months, a 60-year-old man, a chicken breeder, experienced low
      back pain, lower limb weakness predominant on the right side, and urinary
      difficulties, leading progressively to a flaccid paraplegia with sphincter
      impairment. Concomitant poor cognitive performances were noted. MRI showed
      enlargement of the conus terminalis, with a low-intensity signal on T1-weighted
      images, high-intensity signal on T2-weighted images, and areas of intramedullar
      contrast enhancement. A biopsy of the lesion showed macrophages containing yeast
      cells, with PAS and Grocott staining aspects compatible with the presence of
      Histoplasma capsulatum (Hc). A brain MRI showed multiple localizations in the
      brain stem and in both hemispheres with associated edema. Disseminated
      histoplasmosis was confirmed by a biopsy of a sub-maxillary ganglion
      demonstrating a necrotic tuberculoid lymphadenitis containing yeast cells
      resembling Hc. Immune tests disclosed the presence of HTLV1 anti-bodies without
      immunodeficiency nor HIV co-infection. An anti-micotic treatment was started 2
      weeks after surgery, with intra-venous amphotericin B, for 21 days, followed by
      itraconazole, orally for 90 days. Cognitive functions improved significantly in 5
      weeks while paraplegia and sphincter impairment remained unchanged. Seven months
      later, cerebral MR aspects dramatically improved while the conus medullaris
      lesion diminished, and the edematous component disappeared in all areas. Even
      though histoplasmosis is endemic in our region, CNS localization is rare,
      generally in disseminated forms associated with immunodeficiency. Brain
      granulomas are well-known, but spinal cord histoplasmomas are exceptional: only
      four cases have been evaluated by MRI. Unlike our case, spinal cord forms
      generally improve, due to surgery associated with antifungus medication, or
      sometimes due to specific medical treatment alone but with sufficient dosage.

PMID- 11972152
TI  - [Transthoracic transvertebral approach for resection of an anteriorly located,
      calcified meningioma. Case report].
AB  - We report the case of a 61-year-old woman, who developed progressive paraparesia
      over a period of 8 months. Conventional X-rays of the thoracic spine showed an
      intra-spinal calcified lesion at T10. On CT-scan and MRI, the lesion appeared
      anterior to the cord, thus making a posterior approach hazardous. Total resection
      of this calcified meningioma was achieved through a right transthoracic
      transcorporeal approach, under close monitoring of the somatosensory evoked
      potentials. Despite a delayed pseudomeningocele formation requiring an additional
      thoracotomy, outcome after 7 years is excellent with no residual neurological
      deficit. No recurrence was seen on a CT-scan performed two years after the
      surgery. Calcified anterior meningiomas of the spine are rare lesions. Surgical
      outcome has been unfavorable for a long time in relation with posterior or
      postero-lateral approaches. Although anterior transthoracic procedures are
      routinely performed for extradural spinal lesions, this approach is rarely used
      for intradural lesions. A calcified anterior spinal thoracic meningioma should be
      managed like the more frequent calcified thoracic disk hernia, despite the
      increased risk of cerebrospinal fluid effusion requiring subsequent repair.

PMID- 11972153
TI  - [Metastatic meningioma to the first thoracic vertebral body. A case report and
      review of the literature].
AB  - This report describes a case of metastatic meningioma involving the first
      thoracic vertebral body in a 63-year-old woman. The patient was treated
      surgically 10 years earlier for a benign meningioma of the right parietal vault.
      Local recurrence was diagnosed in 1992. Despite the gamma-knife radiosurgery,
      recurrence required surgical treatment in 1999. Histological findings were
      compatible with atypical meningioma (grade II WHO). One year later, the patient
      presented left C8 cervicobrachial neuralgia. Investigation led to discovery of a
      D1 tumor that was a metastasis of the atypical intracranial meningioma. A
      resection of the vertebral T1 body with C7-T2 osteosynthesis was performed with
      an excellent recovery and no postoperative complication.

PMID- 11972154
TI  - Mechanisms of ageing: public or private?
AB  - Ageing--the decline in survival and fecundity with advancing age is caused by
      damage to macromolecules and tissues. Ageing is not a programmed process, in the
      sense that no genes are known to have evolved specifically to cause damage and
      ageing. Mechanisms of ageing might therefore not be expected to be as highly
      conserved between distantly related organisms as are mechanisms of development
      and metabolism. However, evidence is mounting that modulators of the rate of
      ageing are conserved over large evolutionary distances. As we discuss in this
      review, this conservation might stem from mechanisms that match reproductive rate
      to nutrient supply.

PMID- 11972155
TI  - The art and design of genetic screens: Drosophila melanogaster.
AB  - The success of Drosophila melanogaster as a model organism is largely due to the
      power of forward genetic screens to identify the genes that are involved in a
      biological process. Traditional screens, such as the Nobel-prize-winning screen
      for embryonic-patterning mutants, can only identify the earliest phenotype of a
      mutation. This review describes the ingenious approaches that have been devised
      to circumvent this problem: modifier screens, for example, have been invaluable
      for elucidating signal-transduction pathways, whereas clonal screens now make it
      possible to screen for almost any phenotype in any cell at any stage of
      development.

PMID- 11972156
TI  - From sequence to phenotype: reverse genetics in Drosophila melanogaster.
AB  - There has been a long history of innovation and development of tools for gene
      discovery and genetic analysis in Drosophila melanogaster. This includes methods
      to induce mutations and to screen for those mutations that disrupt specific
      processes, methods to map mutations genetically and physically, and methods to
      clone and characterize genes at the molecular level. Modern genetics also
      requires techniques to do the reverse   to disrupt the functions of specific
      genes, the sequences of which are already known. This is the process referred to
      as reverse genetics. During recent years, some valuable new methods for
      conducting reverse genetics in Drosophila have been developed.

PMID- 11972157
TI  - Getting under the skin of epidermal morphogenesis.
AB  - At the surface of the skin, the epidermis serves as the armour for the body.
      Scientists are now closer than ever to understanding how the epidermis
      accomplishes this extraordinary feat, and is able to survive and replenish itself
      under the harshest conditions that face any tissue. By combining genetic
      engineering with cell-biological studies and with human genome data analyses,
      skin biologists are discovering the mechanisms that underlie the development and
      differentiation of the epidermis and hair follicles of the skin. This explosion
      of knowledge paves the way for new discoveries into the genetic bases of human
      skin disorders and for developing new therapeutics.

PMID- 11972158
TI  - Not your father's planarian: a classic model enters the era of functional
      genomics.
AB  - Freshwater planarians were a classic model for studying the problems of
      development and regeneration. However, as attention shifted towards animals with
      more rigid developmental processes, the planarians, with their notoriously
      plastic ontogeny, declined in significance as a model system. This trend was
      exacerbated with the introduction of genetic and molecular approaches, which did
      not work well in planarians. More recently, the heightened interest in stem-cell
      biology, along with the successful application of molecular, cellular and genomic
      approaches in planarians, is re-establishing these fascinating organisms as
      models for studying regeneration and developmental plasticity.

PMID- 11972160
TI  - Science and society: genetic counselling and customary consanguineous marriage.
AB  - Consanguineous marriage is customary in many societies, but leads to an increased
      birth prevalence of infants with severe recessive disorders. It is therefore
      often proposed that consanguineous marriage should be discouraged on medical
      grounds. However, several expert groups have pointed out that this proposal is
      inconsistent with the ethical principles of genetic counselling, overlooks the
      social importance of consanguineous marriage and is ineffective. Instead, they
      suggest that the custom increases the possibilities for effective genetic
      counselling, and recommend a concerted effort to identify families at increased
      risk, and to provide them with risk information and carrier testing when
      feasible.

PMID- 11972159
TI  - Science and society: children and incompetent adults in genetic research: consent
      and safeguards.
AB  - Recent changes to the legal and ethical criteria that govern the inclusion of
      children and incompetent adults in genetic research are likely to lead to
      advances in research, but might leave the rights of the participants in this
      research in need of additional safeguards. Here, we discuss why this might be and
      propose policy considerations that could help to protect the rights of these
      particularly vulnerable groups of research participants.

PMID- 11972161
TI  - Home ventilation.

PMID- 11972162
TI  - A burning topic: tobacco and death.

PMID- 11972163
TI  - Long term follow-up of ventilated patients with thoracic restrictive or
      neuromuscular disease.
AB  - OBJECTIVE: To evaluate the long term effects of home mechanical ventilation (HMV)
      on pulmonary function, nighttime gas exchange, daytime arterial blood gases,
      sleep architecture and functional exercise capacity (6 min walk). Patients with
      respiratory failure attributable to thoracic restrictive disease (TRD)
      (kyphoscoliosis) or neuromuscular disease (NMD) were assessed, ventilated,
      trained and followed in a dedicated unit for the care of patients requiring long
      term ventilation. DESIGN: All patients admitted for home ventilation training
      since 1988 were reviewed. Measurements of lung function, gas exchange during
      wakefulness and sleep, as well as functional exercise capacity, were recorded
      before and immediately after the establishment of HMV. Measurements were repeated
      one to two years, five years and eight to 10 years later. PATIENTS: Seventy-four
      individuals with TRD or NMD who completed the home ventilation training program
      and continued with HMV during all or part of the day for at least one year were
      studied. RESULTS: Forty patients had TRD. The characteristics of these patients
      were (mean   SE) as follows: age 58 2.4 years; vital capacity (VC) 27% 1.6%
      predicted, forced expiratory volume in 1 s (FEV1) 25% 1.5% predicted; FEV1/forced
      VC (FVC) 78% 1.8%. Thirty-four patients had NMD. The characteristics of these
      patients were as follows: age 44 3.1 years; VC 41% 4.9% predicted, FEV1 44 5.3%
      predicted; FEV1/FVC 83% 4.2%. There was a significant improvement in distance
      walked in 6 min (maximum change 51.2 m in patients with NMD and 93.0 m in
      patients with TRD), daytime partial pressure of arterial carbon dioxide (maximum
      change 12.9 mmHg in patients with NMD and 10.4 mmHg in patients with TRD) and
      nighttime partial pressure of arterial carbon dioxide (maximum change 11.7 mmHg
      in patients with NMD and 18.0 mmHg in patients with TRD) over time (P 0.004).
      Ventilation resulted in an improvement in partial pressure of arterial oxygen in
      patients with TRD (68.1 2.8 mmHg to 80.1 3.5 mmHg) and in patients with NMD (52.9
      1.7 mmHg to 65.3 2.1 mmHg), although the change was not statistically significant
      in patients with NMD (P=0.001 in patients with TRD; P=0.105 in patients with
      NMD). The improvement after ventilation was maintained over several years. Sleep
      efficiency (75% 18%, 79% 2.2%), the arousal index (13.4 13 events/h, 28.2 17
      events/h) and the apnea-hypopnea index (10.1 11.3 events/h, 13.9 9.5 events/h)
      did not change with time in either patients with TRD or patients with NMD,
      respectively (P 0.5). CONCLUSIONS: HMV was associated with sustained, long term
      improvements in nighttime and daytime gas exchange in patients with TRD and NMD.
      Function exercise capacity increased in patients with TRD and in a subgroup of
      ambulatory patients with NMD. In patients with TRD, these improvements were
      maintained for up to 10 years after HMV was established.

PMID- 11972164
TI  - Faster onset of bronchodilation with formoterol than with salmeterol in patients
      with stable, moderate to severe COPD: results of a randomized, double-blind
      clinical study.
AB  - OBJECTIVES: To compare the onset and magnitude of bronchodilation after dry
      powder inhalations of formoterol fumarate (Foradil Aerolizer) versus salmeterol
      xinofoate (Serevent Diskus) with respect to normalized (*) forced expiratory
      volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1 AUC*0-1 h).
      DESIGN: A double-blind, double-dummy, multicentre, randomized, placebo
      controlled, single-dose, five-period crossover study. SETTING: Five centres in
      four countries - one centre each in France, Greece and Italy, and two centres in
      the Netherlands. PATIENTS: Forty-seven patients aged 42 to 80 years (mean age
      63.5 years) with chronic obstructive pulmonary disease (COPD) stage II and III,
      and mean baseline FEV1 1.17 L (range 0.56 to 1.77 L). INTERVENTIONS: Patients
      inhaled single doses of formoterol dry powder (12 and 24 mg), single doses of
      salmeterol (50 and 100 mg) and matching placebo on five separate days. MAIN
      RESULTS: The estimates of treatment difference in absolute terms (0.086 L) and
      percentage change from predose baseline (7.8%) for the primary end point, FEV1
      AUC*0-1 h, showed that formoterol 12 mg was statistically significantly superior
      to salmeterol 50 mg (P=0.0044 and P=0.0021, respectively). In addition, both
      doses of formoterol were statistically superior to placebo for both absolute
      improvement and percentage change (P=0.0001). The analysis of secondary variables
      also confirmed the superiority of formoterol over salmeterol. CONCLUSIONS:
      Formoterol is associated with a faster onset of bronchodilation than salmeterol
      in patients with COPD.

PMID- 11972165
TI  - Video-assisted thoracic surgery in spontaneous pneumothorax.
AB  - The proven safety and efficacy of minimal access video-assisted thoracic surgery
      has changed the way that spontaneous pneumothorax is managed. This review
      presents some of the experiences of the decade, discusses the controversies and
      reviews the current video-assisted thoracic surgical management of spontaneous
      pneumothorax.

PMID- 11972166
TI  - Chronic traumatic and congenital diaphragmatic hernias: presentation and surgical
      management.
AB  - BACKGROUND: The diagnosis of chronic diaphragmatic hernias, whether due to
      congenital defects or trauma, may be difficult to make and may rely on clinical
      suspicion in the setting of persistent nondiagnostic radiographic findings.
      Repair is indicated to avoid catastrophic cardiopulmonary compromise and/or
      incarceration of abdominal organs. STUDY OBJECTIVES: To review the varied
      presentations and treatment of chronic diaphragmatic hernia. DESIGN:
      Retrospective review. SETTING: University of Washington and Harborview Medical
      Center, Seattle, Washington. PATIENTS: Between 1997 and 2001, nine patients
      presented with chronic diaphragmatic hernia (two congenital cases, seven post
      traumatic cases). Four cases involved the right diaphragm. The following clinical
      features were noted: asymptomatic, chest radiograph showing bowel herniation
      (n=1); chest wall mass (n=1); asymptomatic with the chest radiograph showing
      marked elevation of hemidiaphragm (n=1); dyspnea with the chest radiograph
      showing marked elevation of hemidiaphragm (n=1); diarrhea and heartburn (n=1);
      generalized gastrointestinal upset (n=1); recurrent pneumonia (n=2); recurring
      effusions (n=4); and dyspnea on exertion (n=5). INTERVENTIONS: Diagnosis was
      confirmed by chest radiograph in two patients, chest computed tomography scan in
      one patient, barium studies in three patients and thoracoscopy in three patients.
      All hernias were repaired via thoracotomy, and two hernias were repaired with
      artificial patch. CONCLUSIONS: Patients with chronic diaphragmatic hernias
      present with a variety of symptoms and radiographic findings. When radiology or
      symptoms suggest bowel involvement, barium studies are appropriate. In other
      cases, chest computed tomography scans and/or thoracoscopy are useful. Repair is
      accomplished through the ipsilateral chest, with primary repair of the diaphragm
      preferred over patch repair.

PMID- 11972168
TI  - [Stress and dietary salt intake in the pathogenesis of hypertension: role of the
      renal and sympathetic nervous system].
AB  - Using the methods of electrophysiology, biochemistry, radioimmunoassay, and
      electron microscopy, changes of sympathetic nervous system and renal function in
      hypertensive SD rats induced by stress and high-salt intake were investigated.
      The results are as follows: (1) Renal plasma flow (RPF) and urinary sodium
      excretion obviously increased in salt-loading rats. Stress could result in marked
      reduction of RPF. (2) Electron micrography showed a dramatic increase in cell and
      mitochondrial volume in the proximal and distal convoluted tubules of high-salt
      diet rats. After stress of two weeks, the cells of the tubule became atrophic and
      mitochondrial volume decreased. (3) The same recovery from the declining renal
      cortical Na-K-ATPase activity in high-salt diet rats could be observed by
      maintained stress. (4) Low frequency (0.2-0.9 Hz) of BP variability was higher in
      stress rats as compared to control. (5) Both plasma renin activity (PRA) and
      angiotensin II (ANG II) levels increased in stress rats, but the decrease in high
      salt diet rats gradually reached the high level of the former in two weeks. (6)
      Increase of BP, fall in RPF, or augment in PRA and ANG II were not observed in
      stress rats subjected to bilateral renal denervation. The above results indicate
      that the renal mechanism mediated by increased renal sympathetic nervous system
      plays an important role in stress- and salt-induced hypertension pathogenesis.

PMID- 11972167
TI  - Role of endogenous carbon monoxide in the pathogenesis of hypotension during
      septic shock.
AB  - A sepsis model induced by cecal ligation and puncture was used to study the role
      of endogenous carbon monoxide in hypotension pathogenesis of rats during septic
      shock. After administration of zinc deuteroporphyrin 2,4-bisglycol (ZnDPBG),an
      inhibitor of heme oxygenase (HO),blood pressure (BP),HO activity and carbon
      monoxide (CO) release from vascular muscle tissue were measured. The results
      showed that BP of sepsis rats, including systolic and diastolic arterial BP,
      decreased significantly while HO activity and CO content were significantly
      increased. In contrast, after administration of ZnDPBG, BP of sepsis rats was
      significantly increased while the HO activity and CO production were
      significantly decreased. These findings suggest that HO activity and CO release
      within vascular musculature are increased during septic shock; inhibition of HO
      may elevate BP of rats during septic shock through a decrease of endogenous CO
      production. It is concluded that endogenous CO derived from vascular muscle cells
      plays an important role in regulating vascular tone, and the up-regulation of HO
      activity followed by subsequent CO production contributes to hypotension
      pathogenesis during septic shock.

PMID- 11972169
TI  - [Effect of lipopolysaccharide on the proliferation of rat VSMCs in vitro].
AB  - In cultured vascular smooth muscle cells(VSMCs) of SD rat, it was found that 1 x
      10(-7) - 1 x 10(-5) kg/L lipopolysaccharide(LPS) markedly stimulated
      proliferation and DNA synthesis of VSMCs in a dose dependent manner (P<0.05).A
      time-dependent marked inhibition in proliferation, DNA synthesis and viability of
      VSMCs (P<0.01)could be obtained by 5 x 10(-4) - 10(-3)kg/L LPS. The inhibitory
      effect of LPS could be prevented by L-NNA, which reduced NO production by
      inhibiting NOS. NO3- and NO2- of LPS group markedly increased(P<0.01):48 h group
      vs 24 h group increased by 9.1%,72 h group vs 48 h group increased by 4.5%. When
      5 x 10(-4) - 10(-3) kg/L LPS was added, positive immunohistochemical staining of
      inductive nitric oxide synthase could be observed. These results suggest that LPS
      of low dose stimulated the proliferation and the DNA synthesis of VSMCs, while
      LPS of high dose markedly inhibited them probably due to the increased NO
      production.

PMID- 11972170
TI  - [ET-1 induces the expression of prooncogene c-fos in cultured neonatal rat
      myocardial cells].
AB  - In the present study, the effect of endothelin-1 (ET-1) on the expression of
      proto-oncogene c-fos in cultured neonatal rat myocardial cells was investigated.
      The results are as follows: ET-1 induced c-fos expression in a dose-dependent
      manner. Selective ET(A) receptor antagonist blocked ET-1-induced responses.
      Protein kinase C(PKC) agonist PMA induced c-fos expression.PKC inhibitor
      staurosporine blocked ET-1 induced c-fos expression. Calcium channel blocker,
      nifedipine did not significantly affect the expression of c-fos induced by ET-1.
      These results suggest that in cultured neonatal cardiomyocytes, ET-1 induced c
      fos gene expression is mediated by ET(A) receptor with the participation of
      protein kinase C, while the voltage-dependent L-type Ca(2+) channel is not
      involved.

PMID- 11972171
TI  - [Effects of myocardial ischemia reperfusion injury on L-arginine/nitric oxide
      system in rat heart].
AB  - Ischemia reperfusion injury (IRI) model of rat heart was prepared by preperfusion
      for 15 min, then a suspension for 45 min and recycling reperfusion for 15 min
      with 30 ml KH buffer. The leakage of lactate dehydrogenase(LDH),protein,
      myoglobin and nitrite (NO2-) in the circular perfusion fluid were measured.
      Myocardial nitric oxide synthase(NOS) activity and L-arginine transport were
      observed. In the IR group, the leakage of LDH,protein, myoglobin and NO2- were
      increased respectively by 4.1,5.4,1 and 1.2 times(P<0.01) and NOS(tNOS, iNOS,
      cNOS) activity by 48.2%,43.2% and 52.1%,(P<0.01,respectively) as compared with
      the control group. L-arginine transport might be mediated by either high- or low
      affinity transport system in cardiac tissue. In the IR group, L-arginine
      transport increased significantly with the V(max) being increased by 48% and 2
      times respectively for the low-affinity and the high-affinity transport as
      compared with control. Michaelis constant (km) was decreased by 47.4% for low
      affinity transport (P<0.05),but not significantly changed for the high-affinity
      transport. These results suggest that the increase of nitric oxide generation
      might result from the increased myocardial NOS activity and L-arginine transport
      during IRI.

PMID- 11972172
TI  - [Intracellular electrophysiological characteristics of visceral nociceptive
      neurons in cortex S I area of cats].
AB  - In the present work we investigated electrophysiological properties of visceral
      nociceptive neurons in the primary somatosensory cortex (SI). Intracellular
      recordings of 851 neurons in the representing area of greater splanchnic nerve
      (GSN) in SI area were made in 22 cats. The neurons showed a variety of modes in
      spontaneous discharges, which could be classified into visceral nociceptive
      neurons (VNNs) and non-visceral nociceptive neurons (NVNNs). VNNs (412) could be
      further divided into specific and non-specific subtypes, with three distinct
      response modes: excitatory, inhibitory, and mixed response. These responses were
      characterized by longer latency and complex responsive fashion. In addition, 85
      single convergence neurons induced by input from GSN and intercostal nerve were
      observed. Neurobiotin was injected into some of the cells by electrophoresis to
      identify the depth and morphology following recordings. The results indicated
      that VNNs were located in the SI area.

PMID- 11972173
TI  - [Role of brain angiotensin II system in subfornical organ-pressor responses].
AB  - We studied the role of brain angiotensin II in subfornical organ-pressor
      responses using urethane-anesthetized, tubocurarine-immobilized rats, and the
      present work obtained the following findings: (1) angiotensin II (A II) induced
      pressor responses by injection into several brain regions: either subfornical
      organ (SFO),nucleus paraventricularis (NPV) or its projection areas, including
      rostral ventrolateral medulla (RVLM),periaqueductal gray matter (PAG) and locus
      coeruleus (LC); (2) SFO pressor responses were markedly attenuated by
      preinjection of [Sar(1),Thr(8)]-A II (ST-A II, an A II antagonist) into bilateral
      NPV or RVLM,while NPV pressor responses were suppressed by ST-A II injection into
      the RVLM; (3) both SFO- and NPV-pressor responses were decreased by ST-A II
      preinjection into bilateral PAGL; and (4) ST-A II preinjection into bilateral LC
      could only attenuate NPV pressor responses without affecting SFO pressor
      responses. Taken together with our previous findings that the RVLM mediates the
      pressor responses of the PAG and LC, the present results indicate that A II
      activates A II ergic neurons in the SFO may evoke pressor responses by acting
      upon RVLM through NPV and NPV- PAG -RVLM system. Whereas NPV- LC- RVLM system was
      not involved in the SFO pressor responses.

PMID- 11972174
TI  - [Study of formula for calculating body surface areas of the Chinese adults].
AB  - The body surface area of 100 Chinese adults (50 for each sex) was measured with
      the paper cast method and compared to the results estimated by the Stevenson's
      "height-weight-surface" formula. Our results shows that Stevenson's formula is no
      longer suitable for the Chinese. Our formulae for Chinese are as follows:
      SI=0.0061 x H + 0.0124 x W - 0.0099 (for both sexes), SII=0.0057 x H + 0.0121 - W
      + 0.0882 (for male), SIII=0.0073 H + 0.0127 x W - 0.2106 (for female) H: body
      height, W: body weight, S: body surface area

PMID- 11972175
TI  - [Opioid mu receptors in caudate nucleus contribute to electroacupuncture and Sm I
      generating inhibition on nociceptive responses of Pf neurons].
AB  - The present experiments aimed to investigate whether the caudate nucleus (Cd) was
      involved in cortical sensorimotor area I (Sm I) generating descending modulation
      of the parafascicular nucleus (Pf) in acupuncture analgesia (AA), and what type
      of opiate receptors in Cd were involved. It was found that nociceptive responses
      of Pf neurons could be inhibited by electroacupuncture (EA) and excitation of Sm
      I before lesion of Cd, but not after lesion. After microinjection of naloxone
      beta-FNA, the specific antagonist for opioid mu receptors, into Cd,the inhibitory
      effect of EA or activation of Sm I on nociceptive responses of the Pf neurons was
      abolished, but it was not influenced by microinjection of nor-BNI and ICI174,864,
      the specific antagonists for opioid kappa and delta receptors, respectively.
      Together with our previous findings that EA could activate cortical neurons to
      participate in descending modulation of activities of Pf neurons, the present
      results suggest that Cd is associated with Sm I generating descending inhibition
      on nociceptive responses of Pf neurons in AA, and it is most likely that opiates
      in Cd may be involved in this inhibition through mu but not kappa or delta
      receptors.

PMID- 11972176
TI  - [Effects of glutamate on transient outward potassium current of dissociated
      hippocampal neurons in ca1 sector in rats].
AB  - The effects of glutamate on the transient outward potassium current of
      dissociated hippocampal CA(1) neurons of 7-10 d rats were studied by the whole
      cell patch clamp technique. It was found that glutamate could block the transient
      potassium current in a dose- and time-dependent manner. The effect was partly
      voltage-dependent. These results suggest that glutamate may decrease the membrane
      conductance of K(+) channels in hippocampal neurons.

PMID- 11972177
TI  - [Effect of ACTH on the expression of somatostatin and c-fos in the spinal cord
      and formalin evoked pain response].
AB  - In the present study, the effect of ACTH on the expression of somatostatin and c
      fos in the spinal cord and formalin induced pain responses in rats were studied
      using immunohistochemistry and in situ hybridization. The results showed that
      subcutaneous injection of formalin in the right hindpaw increased c-fos-like
      immunoreactivity (FLI), somatostatin-like immunoreactivity (Som-LI), Som-LI/FLI
      and perprosomatostatin mRNA (PPS-mRNA) in neurones of right spinal dorsal horn
      and significantly enhanced pain intensity rating. ACTH decreased the FLI,Som-LI,
      Som-LI/FLI and PPS-mRNA levels of the spinal cord evoked by formalin. The
      decrease of c-fos or Som level due to intrathecal injection of ACTH in rats with
      chronic pain was prevented by injection of cyproheptadine, but not by bicuculline
      and naloxone. The results indicate that the serotonin receptor may be involved in
      ACTH induced analgesia.

PMID- 11972178
TI  - Increased phosphorylation of DARPP-32 by D1 agonistic action of l-stepholidine in
      the 6-OHDA-lesioned rat striatum.
AB  - In order to explore the characteristics of l-stepholidine (SPD) activating the
      postsynaptic D(1) receptors, the effects of SPD on DARPP-32 phosphorylation in
      vivo with back-phosphorylation assay and on the postsynaptic D(1) receptor
      densities with radioligand assay were observed in the striatum of 6-OHDA-lesioned
      rat. The results showed that following subcutaneously administration of 20 or 40
      mg/kg SPD for 21 d,  (32)P  phosphate incorporation into the DARPP-32 protein in
      the denervated striatum showed a 50% reduction (P<0.01) vs the intact striatum,
      indicating an increase of DARPP-32 phosphorylation in vivo in the denervated
      striatum. However,the D(1) receptor B(max) was decreased from 385.0+/-26.1 to
      319.7+/-20.1 fmol/mg protein. It is suggested that D(1) agonist action of SPD
      decreases the D(1) receptor density but increases the phosphorylation of DARPP-32
      in the striatum of 6-OHDA-lesioned rat, which may be responsible for the
      regulation of D(1) receptor signal transduction in brain neurons.

PMID- 11972179
TI  - [A quantitative study on the synaptic ultrastructural alterations in visual
      cortex in the maintenance of LTP].
AB  - The ultrastructure of synapses three hours after formation of long-term
      potentiation (LTP) was examined in the local microslices of visual cortical brain
      slices of 18-20 d rats. Slices without potentiating stimulation which were
      similarly incubated served as controls. The following structural changes were
      examined using a graph analyzer: (1) synaptic cleft width; (2) thickness of the
      postsynaptic densities(PSD); (3) length of the active zones; and (4) curvature of
      the synaptic interface. The number of synapses of different types in layer II/III
      of visual cortex was quantified by double-blind scoring procedures. The various
      counts were converted to the number of synapses per unit volume using
      stereological quantitation method. Analysis of variance was used for statistical
      evaluation. Our results suggest that field potentials reached their peak values
      at about one and a half hours after tetanus and could be maintained as long as
      three hours without decay. In comparison with the control groups, synaptic cleft
      width, thickness of PSD, surface density per unit volume(Sv) of the active zones,
      curvature of the synaptic interface, numeric density per unit volume (Nv) of all
      synapses, spine synapses and the Nv of perforated synapses were all increased
      significantly. These data suggest that the increase of Sv of active zones and the
      increase of the curvature of synaptic interface may be the morphological feature
      characterizing the maintenance of LTP, in addition to the formation of perforated
      synapses.

PMID- 11972180
TI  - [Effects of endogenous nitric oxide on pulmonary artery hypertension and lung
      injury induced by endotoxin].
AB  - Changes in mean artery pressure (MAP), pulmonary artery pressure (PAP) and nitric
      oxide (NO) contents in inflow and outflow pulmonary blood(IPB,OPB) were observed
      after endotoxin lipopolysacchride (LPS) was injected i.v. in rabbits. Changes of
      PAP and lung injury were also observed after inhibitor of NO synthesis L-NNA or
      inhibitor of inducible NO synthesis AG was pre-injected by vein. The results
      showed that MAP decreased significantly after LPS administration, and 0.5-2h
      later PAP showed some increase (P<0.05) being maximum at PAP (1h) during which
      the content of NO in IPB was detectably decreased but NO in OPB did not. NO
      contents in OPB at 3h and in IPB and OPB at 5h increased significantly following
      LPS administration as compared with control.PAP correlated negatively with NO in
      IPB at the time before and 1h after LPS injection, which did not exist at 3 and
      5h after LPS injection. After L-NNA pretreatment, when PAP elevated
      significantly, the MDA content in IPB and OPB also showed significant increase,
      while animal survival rate fell significantly. Light microscopic examination
      showed severe alveolar atelectasis, significant congestion and sequestration of
      leukocytes in lung tissue. When pretreated with AG, MAP elevated significantly in
      3-5h, PAP remained unchanged. The MDA content in blood was lower at 5h in the LPS
      injected group with less pathological changes in lung tissue at 5h compared with
      the LPS group. The above results suggested that there was pulmonary hypertension
      in the early stage after endotoxin administration. The decrease of NO content in
      IPB may be one of the mechanisms underlying pulmonary artery hypertension(PAH).NO
      seemed to alleviate PAH and lung injury at the early stage after endotoxin
      administration. When iNOS was induced at the later stage, NO contributed to lung
      injury caused by endotoxin.

PMID- 11972181
TI  - [Effect of human inhibin alpha-fragment 1-32-Tyr(P33) on apoptosis of cultured
      rat corpus luteal cells].
AB  - Recently, increasing evidence suggests that alpha inhibin or related proteins may
      be a functional regulator in the ovary, which is independent of hetero-dimer
      inhibin. In our previous study, it was demonstrated that human inhibin alpha-N
      terminal fragment Tyr-1-32 (P(33)) significantly inhibited progesterone
      production by rat corpus luteal cells in vitro, and stimulated luteal functional
      regression and apoptosis in vivo. In the present work, the action of P(33) on
      apoptosis was further studied in vitro in cultured rat CL cells. Gel
      electrophoretic analysis for detection of oligonucleosomal DNA fragmentation, AO
      EB or PI assays and flow cytometry were used to observe the action of P(33) on
      the occurrence of spontaneous apoptosis by collagenase-DNase dispersed CL cells,
      obtained from PMSG-hCG induced pseudopregnant rats. The results showed that P(33)
      (1 microg/ml) stimulated spontaneous apoptosis of CL cells. The inhibitor of
      tyrosine protein kinase, genistein (50 microg/ml),inhibited P(33) enhanced
      spontaneous apoptosis. RNA and protein synthesis inhibitors cycloheximide (Cyx,50
      microg/ml) and actinomycin D(Act D,50 microg/ml) did not protect the cells from
      apoptosis stimulated by P(33). The results suggest that P(33) stimulates
      spontaneous apoptosis in cultured rat CL cells with the involvement of tyrosine
      specific protein kinase system. This work provides further evidence for the
      hypothesis that alpha inhibin or related protein might be a functional regulator
      in the ovary.

PMID- 11972182
TI  - [Studies on respiratory phase switching effects of Botzinger complex].
AB  - The effects of electrical stimulation of Botzinger complex (Bot.C) on respiratory
      rhythm were investigated in 40 urethane anesthetized adult rabbits. The results
      were as follows. (1) A short train stimulation delivered in the early inspiratory
      phase produced a transient inhibition of phrenic discharge. The stimulus, when
      delivered in the mid or late inspiratory phase, could cause a premature
      termination of the inspiratory phase ("inspiratory off-switch") and a switching
      to the expiratory phase, which was accompanied with the reduced duration of the
      consecutive expiratory phase. There was a negative linear correlation between the
      threshold intensity of inspiratory off-switching and delivery time of
      stimulation. (2) A short train stimulation delivery in the expiratory phase
      elicited a transient phrenic discharge. The discharge in the late expiratory
      phase was followed by a premature onset inspiration. This effect was also
      dependent on the strength and delivery time of the stimulus. The results suggest
      that the Bot.C is involved in the central control of respiratory phase-switching.

PMID- 11972183
TI  - [Response and membrane properties of nociceptive neurons in SI to stimulation of
      VPL].
AB  - Intracellular potentials were recorded from nociceptive neurons(NCNs) in primary
      somatosensory cortex area (SI) of cats in response to stimulation of ventral
      posterior lateral nucleus (VPL). When the polarizing current injected into NCNs
      was < or = 1.0 nA, the I-V curve was quite linear (r=0.96). However, when the
      polarizing current was >1.0 nA, rectification rendered the I-V curve sigmoid in
      shape. The rectification in NCNs was more prominent than that in NNCNs. Rm,tau
      and Cm of the NCNs were obviously larger than those of NNCNs (P<0.01 or P<0.05).
      The responses of NCNs evoked by stimulating VPL and SN might be similar or
      different. Implications of the differences of NCN and NNCN were discussed.

PMID- 11972184
TI  - [Opioid receptor mediated modulation of intrahippocampal enkephalin induced
      cellular immune function].
AB  - In the present work, the effect of intrahippocampal microinjection of opioid
      receptor antagonist naloxone on the enhancement of cellular immune responses
      induced by enkephalin was studied in rat. The results showed that (1) the
      proliferation activity of splenic lymphocytes stimulated by Con A and natural
      killer (NK) cell activity were decreased with microinjection of 1 microl
      lipopolysaccharide (LPS,50 ng/microl) into bilateral hippocampus; (2) the
      decrease of cellular immune responses induced by LPS could be inhibited by a
      preceding intrahippocampal injection of 1 microl met-enkephalin (10 microg/1
      microl); (3) the enhancement of cellular immune responses induced by met
      enkephalin could be blocked by an opioid receptor antagonist naloxon (10
      microg/microl); and (4) cellular immune responses were also inhibited when
      naloxon was injected intrahippocampally alone. The above results suggest that the
      enhancement of cellular immune responses induced by enkephalin was mediated by
      opioid receptors in hippocampus.

PMID- 11972185
TI  - [Testosterone induction of metallothionein in accessory genital organs of male
      domestic cats].
AB  - Orchidectomy of cats resulted in a decrease of metallothionein (MT) in the
      dorsolateral and ventral lobes of the prostate and in the urethral gland to 21.2%
      (P<0.01), 88.4% (P>0.05) and 18.5% (P<0.01) of those of intact domestic cats
      respectively. MT content in the dorsolateral lobe and urethral gland was not
      restored in orchidectomized cats injected with sesame oil. After injection of a
      single subcutaneous dose of 10 microg/kg bw of testosterone (T) for 3 d in
      succession, the MT contents in the two glands were restored respectively to 69.3%
      and 59.4% of the intact cats. With an increase of T dose to 5, 10, 15, 20, 25
      microg/kg bw, plasma T and MT contents in the dorsolateral lobe of prostate and
      urethral gland increased accordingly. Plasma T concentrations were positively
      correlated with MT contents in the dorsolateral lobe of prostate and urethral
      glands (P<0.01). Thus biosynthesis of MT in the dorsolateral lobe of prostate or
      in urethral gland could be induced by a stimulatory dose of T of 20 microg/kg bw.

PMID- 11972187
TI  - Laparoscopic total mesorectal excision.
AB  - After total mesorectal excision for rectal cancer was introduced in 1982, local
      recurrence rates decreased to 5%. These results were found to be reproducible;
      therefore, the technique became standard for the treatment of rectal cancer.
      Laparoscopic surgery for curable colorectal malignancy is still considered
      investigational. Indeed, the United States National Cancer Institute (NCI) trial
      excludes rectal carcinoma. The application of laparoscopy to rectal carcinoma
      must compete with total mesorectal excision, which has obtained favorable results
      in the last decade. In this review, we assess the adequacy of laparoscopic total
      mesorectal excision, describe the techniques (both anterior resection and
      abdominoperineal resection), and discuss their potential advantages.

PMID- 11972189
TI  - Chronic cough due to gastroesophageal reflux disease: efficacy of antireflux
      surgery.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) can be overlooked as the cause
      of chronic cough (CC) when typical gastrointestinal symptoms are absent or
      minimal. We analyzed the outcomes of Nissen fundoplication (NF) for patients who
      failed medical therapy for CC attributable only to GERD (G-CC). We performed a
      prospective outcome evaluation of 21 consecutive patients with G-CC undergoing NF
      from 1997 to 2000 at a tertiary care university hospital. MATERIALS AND METHODS:
      Twenty-one patients without prior antireflux surgeries had G-CC diagnosed by a
      clinical profile and 24-h pH monitoring showing a cough-reflux correlation.
      Respiratory symptoms alone were present in 53% of patients. NF was performed when
      G-CC persisted despite intensive medical therapy, including an antireflux diet.
      Preoperatively, all patients underwent 24-h pH monitoring, esophageal manometry,
      barium swallow, gastric emptying study, bronchoscopy, and upper endoscopy. NF was
      utilized in all cases, laparoscopically in 18. Before and after surgery, patients
      graded their cough severity using the Adverse Cough Outcome Survey (ACOS).
      Quality of life was measured using the Sickness Impact Profile (SIP). RESULTS:
      Postoperatively, 18 patients (86%) reported an improvement of their cough. G-CC
      considerably improved in 16/21 patients (76%), with complete resolution in 13
      patients (62%). Mild to moderate improvement was found in 2 patients (10%).
      Patient-reported cough severity (ACOS) and quality of life (SIP) both
      significantly improved early (6-12 weeks) postoperatively and persisted during
      the long-term (1 year) follow-up. The average hospital length of stay was 1.78 +/
      0.2 (l-4) days for the laparoscopic (n = 18) and 6.3 +/- 1.2 (4-8) days for the
      open surgery (n = 3) groups. CONCLUSION: Twenty-four-hour esophageal pH
      monitoring is a valuable tool for preoperative cough-reflux correlation.
      Antireflux surgery is effective in carefully selected patients whose refractory
      CC is attributable only to GERD. NF controls the severity of cough while
      improving the quality of life. Outcomes are further enhanced using laparoscopic
      procedures with shorter hospital stays.

PMID- 11972188
TI  - Gastroesophageal reflux disease (GERD) and chest pain. Results of laparoscopic
      antireflux surgery.
AB  - BACKGROUND: Laparoscopic fundoplication cures heartburn and regurgitation in
      patients with gastroesophageal reflux disease (GERD) but its effect on the chest
      pain that is also experienced by some patients is less clear. Confusion stems
      from the fact that it is difficult to determine preoperatively whether the chest
      pain is actually caused by the reflux. Therefore, we designed a study in patients
      with GERD and chest pain that would assess the value of pH monitoring in
      establishing a correlation between the symptom and the disease, the predictive
      value of pH monitoring on the results of surgical treatment, and the outcome of
      laparoscopic fundoplication on chest pain in patients with GERD. METHODS: Of 487
      patients who underwent laparoscopic fundoplication for GERD at our institution
      between October 1992 and July 2000, 165 (34%) complained of chest pain in
      addition to heartburn and regurgitation. Their symptoms had been present for an
      average of 118 months. The pH monitoring tracings were analyzed for a correlation
      between episodes of reflux and chest pain. The mean length of follow-up was 13
      months. RESULTS: Among the 165 patients with chest pain, the relationship between
      pain and reflux during pH monitoring was as follows: 39 patients (group A)
      experienced no chest pain during the study; in 28 patients (group B), chest pain
      correlated with reflux in <40% of instances; in 98 patients (group C), chest pain
      correlated with reflux in ?40% of instances. Chest pain improved postoperatively
      in 65% of group A patients, 79% of group B patients, and 96% of group C patients
      (group C vs A and B: p <0.05). Heartburn and regurgitation resolved or improved
      in 97% and 95% of patients, respectively. CONCLUSIONS: These data show that pH
      monitoring helped to identify a relationship between chest pain and reflux; and
      when the two coincided, the chest pain was relieved by antireflux surgery.

PMID- 11972191
TI  - Needlescopic fundoplication.
AB  - BACKGROUND: Minimally invasive surgery continues to evolve, with an emphasis on
      developing new techniques and applying new technology to surgical procedures. The
      purpose of this study was to compare the short-term outcomes of needlescopic
      fundoplication with those of conventional laparoscopic fundoplication. METHODS:
      Between January 1999 and June 2000, 38 needlescopic fundoplications were
      performed, and the short-term outcomes for these patients were compared with
      those for a contemporary matched cohort of patients who had undergone a
      conventional laparoscopic fundoplication. RESULTS: There was a nonsignificant
      trend toward decreased operative time (143.4 to 127 min; p = 0.13), blood loss
      (54.3 to 48 ml; p = 0.30), narcotic requirements (29.5 to 19.5 morphine
      equivalents; p = 0.32), and length of hospital stay (1.78 to 1.49 days; p = 0.10)
      in the needlescopic group. There were no significant differences in
      intraoperative complications (2.6% vs 2.6%; p = 1.0). Two needlescopic cases were
      converted to laparoscopic cases because of obesity. Postoperatively, there were
      no significant differences in rates of early dysphagia (7.9% vs 7.9%), bloating
      (13.2% vs 5.3%; p = 0.43), or other complications (5.3% vs 5.3%) between the
      groups. There was a significant reduction in mean operative time for needlescopic
      fundoplication after the first four cases (166 +/- 44 vs 120 +/- 32 min; p =
      0.03). CONCLUSIONS: Needlescopic fundoplication poses no disadvantage, and it
      offers the added cosmetic benefit of smaller incisions.

PMID- 11972190
TI  - Dysphagia and quality of life after laparoscopic Nissen fundoplication in
      patients with and without prosthetic reinforcement of the hiatal crura.
AB  - BACKGROUND: Recurrent hiatal hernia with or without intrathoracic wrap migration
      ("slipping Nissen") is one of the most common complications after laparoscopic
      Nissen fundoplication (LNF). Therefore, we decided to reinforce the hiatal crura
      using a prosthetic mesh prosthesis in an attempt to reduce recurrent hiatal
      hernia. METHODS: The current nonrandomized study compares the surgical outcome,
      including quality of life data [Gastrointestinal Quality of Life Index (GIQLI)]
      and subjective degree of dysphagia, in a total of 200 patients with (n = 100) or
      without (n = 100) mesh prosthesis for a follow-up for at least 1 year. RESULTS:
      There are no significant differences between groups in postoperative DeMeester
      score or lower esophageal sphincter pressure. In the group without mesh
      prosthesis, in 6 cases laparoscopic redo surgery was necessary due to severe and
      persistent dysphagia (n = 2) or a slipping Nissen (n = 4). Additionally, in 5
      patients we found recurrent hiatal hernia, but patients have been without
      symptoms for at least 1 year. In the group with mesh prosthesis, laparoscopic
      refund application was performed in only 1 patient due to a slipping Nissen. In
      this group, recurrent hiatal hernia was not found in endoscopy. After
      laparoscopic antireflux surgery, GIQLI showed an equal improvement in both groups
      with an outcome comparable to that for healthy individuals. Postoperative
      dysphagia was significantly higher in the group with mesh prothesis within the 3
      first months after surgery. One year after surgery no differences could be found.
      CONCLUSIONS: Our findings suggest that LNF with reinforcement of the hiatal crura
      reduces the risk of recurrent hiatal hernia with or without wrap migration. In
      addition, LNF with mesh prosthesis improves patient's quality of life
      significantly to the same level as that in patients without mesh prosthesis.
      Postoperative dysphagia is higher in the early period after surgery, but this is
      only temporary. Long-term results of a randomized trial must be obtained before a
      general standardization can be discussed.

PMID- 11972192
TI  - Fundus-first laparoscopic cholecystectomy.
AB  - BACKGROUND: Fundus-first dissection (FFD) is an established technique to deal
      with difficult open cholecystectomies. Although the indications for such an
      approach are similar for laparoscopic cholecystectomy (LC), FFD is not widely
      practiced because of difficulties that arise with liver retraction, the
      dissection of dense adhesions, or obscured cystic pedicles, often necessitating
      conversion to an open procedure. METHODS: The aim of this study was to evaluate
      the indications for FFD and the technical aspects of the procedure in cases with
      a difficult cystic pedicle. Prospectively collected data and video recordings of
      cases of fundus-first laparoscopic cholecystectomy (FFLC) were analyzed. The
      great majority were difficult cases, so we also reviewed the safety aspects of
      this approach and assessed its effect on the conversion rate. RESULTS: FFLC was
      resorted to in 35 cases (5%) of 710 consecutive LCs with difficulty grade II (two
      cases), III (13 cases), or IV (20 cases). There were 16 male patients (46% vs 9%
      males in the whole), and the mean age was 56 years (ranges, 28-87). The reasons
      for FFD were dense adhesions preventing the exposure of the cystic pedicle in 14
      cases, large Hartmann's pouch stones in 10 cases, short dilated cystic ducts in
      six cases, and Mirizzi syndrome in three cases. Two cases had contracted "burn
      out" gallbladders. Intraoperative cholangiography (IOC) was possible in 24
      patients, failed in 10 (29%), and was not attemped in one. Seven patients had
      bile duct stones and required bile duct exploration. FFLC was completed in 31
      patients, 28 of whom were seriously considered for conversion prior to commencing
      FFD. Conversion was still necessary after trial FFD in four cases (11%) two with
      Mirizzi abnormalities, one with bile duct stones, and one with dense adhesions.
      The mean operative time was 125 min, (range, 50-230). There were no operative or
      technique-related complications. CONCLUSION: FFLC is feasible and is a safe
      option for cases with a difficult cystic pedicle. Its use reduced the conversion
      rate of the series from a potential 5.2% to 1.2%, However, subtotal
      cholecystectomy or conversion must not be delayed if, after the neck of the
      gallbladder is reached the anatomy is still unclear.

PMID- 11972194
TI  - A new technique for two-trocar laparoscopic cholecystectomy.
AB  - BACKGROUND: New techniques for laparoscopic cholecystectomy (LC) that reduce the
      number of trocars or use very thin instruments have been devised with the goal of
      further minimizing surgical invasiveness. METHODS: We performed two-trocar LC
      using an original new technique in 70 consecutive patients. A 10-mm trocar and a
      5-mm trocar were inserted in the subumbilical and epigastrium positions,
      respectively. A 2-mm grasper forceps was inserted directly without a trocar below
      the costal margin. The fundus of the gallbladder was ligated and lifted up with a
      folded 0 silk string and a 16-gauge vessel cannula. RESULTS: The mean operative
      time was 73.2 +/- 23.5 min. A third trocar was added in two cases. None of the
      patients required conversion of the procedure to an open cholecystectomy, and
      there were no intraoperative complications. CONCLUSION: Based on our experience,
      we think that this technique is as safe and effective as the classic four-trocar
      technique; moreover, it has a cost benefit.

PMID- 11972193
TI  - Endolaparoscopic rendezvous treatment: a satisfying therapeutic choice for
      cholecystocholedocolithiasis.
AB  - BACKGROUND: There are many different strategies for the treatment of the main
      bile duct lithiasis. When lithiasis of the biliary tract is suspected at a
      preoperative stage, we can treat patients with sequential treatment: endoscopic
      netrograde cholangiopancreatography followed by laparoscopic cholecystectomy. If
      common bile duct-lithiasis is recognized at an intraoperative stage, many options
      for treatment exist, one of which is intraoperative retrograde endoscopic
      sphincterotomy (ES) (laparoendorendezvous). METHODS: We report our experience
      using the aforementioned technique with 58 patients affected by cholelithiasis
      and complex Common bile duct disease who underwent laparoscopic cholecystectomy
      and intraoperative ES consecutively from March 1996 to May 2000. Of the 58
      patients, 43 were affected by cholecystocholedocolithiasis: 12 by previously
      described lithiasis plus stenosant papillitis, 2 also by a pancreas head cancer,
      and 1 by cancer of the papilla. RESULTS: The combined technique was performed in
      86% of the cases. Six patients required conversion to open surgery. In two other
      patients, laparoscopic choledocotomy was performed with positioning of a Kehr
      tube for an ampulla-impacted lithiasis. CONCLUSIONS: Intraoperative ES offers a
      valid approach to the treatment of cholecystocholedocolithiasis in one session.
      Furthermore, it represents a valid alternative to transcholedocical laparoscopic
      treatment of cholelithiasis and complex common bite duct pathology.

PMID- 11972195
TI  - Laparoscopic cholecystectomy without routine operative cholangiography does not
      result in significant problems related to retained stones.
AB  - BACKGROUND: This study investigated whether failure to identify common bile duct
      stones at laparoscopic cholecystectomy results in significant postoperative
      complications related to retained stones. METHODS: We performed a retrospective
      analysis of the case notes of 377 consecutive patients undergoing laparoscopic
      cholecystectomy without routine operative cholangiography under a single surgeon
      in a district general hospital between 1995 and 1999. Highly selective
      preoperative endoscopic retrograde cholangiopancreatography (ERCP) was employed
      to identify and manage suspected bile duct stones in pancreatitis, jaundice,
      persistently elevated liver function tests, or a dilated common bile duct.
      RESULTS: Eighteen (4.8%) of 377 patients presented postoperatively with
      symptoms/signs suggesting biliary pathology. Two (0.5%) were confirmed to have
      retained duct stones/debris (ultrasound/ERCP); both recovered with conservative
      treatment. Only 1 patient of 274 (0.4%) without preoperative ERCP subsequently
      presented with a symptomatic retained stone, the other having been stented
      preoperatively. CONCLUSIONS: Highly selective preoperative ERCP without routine
      operative cholangiography is not associated with a significant increase in
      morbidity/mortality related to retained stones following laparoscopic
      cholecystectomy.

PMID- 11972196
TI  - Laparoscopic vs open hemicolectomy for colon cancer.
AB  - BACKGROUND: The role of laparoscopic resection in the management of colon cancer
      is still a subject of debate. In this clinical study, we compared the
      perioperative results and long-term outcome for two unselected groups of patients
      undergoing either laparoscopic or open hemicolectomy for colon cancer. METHODS:
      This prospective nonrandomized study was based on a series of 248 consecutive
      patients operated on by the same surgical team using the same type of surgical
      technique for right (RHC) and left (LHC) hemicolectomy, excluding segmental
      resections; the only difference was the type of access, which was either
      laparoscopic or open. The choice of type of access was left up to the patient
      after he or she had read the informed consent form. Operative time, length of
      stay, complications, and long-term outcome for the two groups were compared.
      Follow-up time ranged between 12 and 92 months (mean, 42). RESULTS: Between March
      1992 and January 2000, 140 patients underwent a laparoscopic hemicolectomy (55
      RHC and 86 LHC); at the same time, 107 patients (44 RHC and 63 LHC) were treated
      via an open approach. There were no conversions to open surgery in the
      laparoscopic RHC group, but six patients (7%) in the laparoscopic LHC group were
      converted. The mean operative time for laparoscopic surgery was significantly
      longer than the time for open surgery (190 vs 140 min for RHC, 240 vs 190 min for
      LHC,); however, with increasing experience, this time decreased significantly.
      The mean hospital stay for the patients who underwent laparoscopic procedures was
      significantly shorter in both the RHC and the LHC groups (9.2 vs 13.2 days for
      RHC, 10.0 vs 13.2 days for LHC). No statistically significant difference between
      the two laparoscopic and open groups was observed for the major complication rate
      (1.9% vs 2.3% for RHC, 7.5% vs 6.3% for LHC). The patient in the laparoscopic RHC
      group were lost to follow-up. The local recurrence rate was lower after
      laparoscopic surgery in both arms (5.4% vs 9% for RHC, 1.5% vs 7.5% for LHC), but
      the differences were not statistically significant. Two port site recurrences
      were observed in the laparoscopic groups, one after RHC (2.7%) and one after LHC
      (1.5%). Metachronous metastases rates were similar for the two groups (16.2% vs
      15.1% for RHC, 4.4% vs 5.7% for LHC). Cumulative survival probability at 48
      months after laparoscopic RHC was 0.865, as compared to 0.818 after open surgery,
      and 0.971 after laparoscopic LHC, as compared to 0.887 after open surgery.
      CONCLUSION: These results suggest that laparoscopic hemicolectomy for colonic
      cancer can be performed safely, with morbidity, mortality, and long-term results
      comparable to those of open surgery.

PMID- 11972197
TI  - The management of leaking rectal anastomoses by minimally invasive techniques.
AB  - BACKGROUND: The salvage of a leaking rectal anastomosis has been reported in
      selected cases. Herein we present our experience in the management of rectal
      anastomotic dehiscence by minimally invasive techniques. METHODS: A total of 94
      patients underwent anterior rectal resection for rectal cancer in an 18-month
      period. The operation was laparoscopic-assisted in 76 cases (81%). RESULTS:
      Clinical anastomotic dehiscences occurred in 10 cases (10.6%). Conservative
      therapy, including the percutaneous drainage of pelvic abscesses, was successful
      in three cases. Among the seven patients who required reoperation, the
      anastomosis was taken down in only one case. In four of these cases, the
      reoperation was performed laparoscopically, including peritoneal lavage and the
      creation of a diverting stoma. There were no complications resulting from the use
      of laparoscopy in the early postoperative period. Closure of the stoma was
      possible in eight patients. CONCLUSIONS: The salvage of a leaking rectal
      anastomosis is feasible in the vast majority of these cases (80%). The
      combination of laparoscopy and interventional radiology is a good alternative to
      laparotomy in patients who have had previous laparoscopic rectal excision.

PMID- 11972198
TI  - Results of laparoscopically assisted colon resection for carcinoma.
AB  - BACKGROUND: Surgical resection is the primary treatment for colorectal carcinoma.
      Laparoscopically assisted colon resection technically is feasible for both benign
      and malignant disease. However, the role of laparoscopically assisted colon
      resection for carcinoma is controversial. METHODS: We prospectively studied our
      first 100 patients with colorectal carcinoma who successfully underwent
      laparoscopically assisted colon resection for the carcinoma. RESULTS: The
      pathologic stages were Dukes' categories A-16, B-52, C-25, and D-7. Operative
      mortality and morbidity were 2% and 22%, respectively. During a mean follow-up
      period of 40.3 months, recurrence by stage was zero patients with stage A
      disease, five patients with stage B disease, nine patients with stage C disease.
      Thirteen of these patients died as a result of their disease. At this writing, 60
      patients are alive without evidence of disease, and 23 have completed the study
      disease free after more than 60 months. The 5-year survival probabilities by
      stage were 100% for stage A, 76.8% for stage B, and 51.7% for stage C.
      CONCLUSIONS: Laparoscopically assisted colectomy for cancer can be performed
      safely. The recurrence rate after laparoscopically assisted resection appears to
      be at least as good as after open resection. Results from ongoing prospective,
      randomized trials are needed to confirm these findings.

PMID- 11972199
TI  - Intraperitoneal hypothermia during surgery enhances postoperative tumor growth.
AB  - BACKGROUND: Recent work has shown that intraoperative hypothermia is a
      significant source of surgical trauma, with wide-ranging physiological and
      immunological sequelae. The aim of this study was to examine the effects of
      intraperitoneal hypothermia during laparoscopy on tumor growth in an animal
      model. METHODS: Thirty WAG rats were randomized to undergo anesthesia alone (n =
      10), insufflation with cold carbon dioxide (CO2) (n = 10), or insufflation with
      warm CO2 (n = 10). During insufflation, 1 x 105/ml CC531s colon cancer cells in
      suspension were injected into the peritoneal cavity. The control group was
      anesthetized and tumor cells were injected without insufflation. After 3 weeks,
      total tumor weight and the extent of tumor spread, as assessed by the modified
      Peritoneal Cancer Index (PCI), were compared at autopsy. RESULTS: Laparoscopy
      with cold CO2 resulted in a significant reduction in local and core body
      temperatures (p <0.05). Tumor growth in both groups that underwent CO2
      pneumoperitoneum was significantly increased compared with the group that did not
      (p <0.0001, control vs warm CO2 and cold CO2). There was significantly more tumor
      growth in the rats insufflated with unwarmed CO2 than in the normothermic group
      (mean total tumor 0.01 g +/- 0.03 vs. 0.043 g +/- 0.07; p = 0.025 Mann-Whitney U
      test). Tumor spread as shown by the PCI scores was less in the warm gas group
      than it was in the animals insufflated with cold gas (151 vs 266). CONCLUSIONS:
      These data demonstrate that the peritoneal insufflation of CO2 enhances tumor
      growth and that the prevention of perioperative hypothermia during laparoscopy
      attenuates tumor growth. This effect may be partially mediated by the increased
      peritoneal trauma that results from insufflation with cold gas.

PMID- 11972200
TI  - The contribution of laparoscopy to the treatment of gastric cancer.
AB  - BACKGROUND: Laparoscopy plays a role in the preoperative diagnosis of gastric
      cancer, particularly in determining the location and extent of the neoplasia. In
      addition to its use in staging, laparoscopy is indicated for the gastric
      resection of T1-T2, and its middle- and long-term results are comparable to those
      obtainable with open surgery. Herein we describe our experience with the
      laparoscopic resection of gastric carcinomas, including the dissection of lymph
      nodes and the Billroth II reconstruction of digestive continuity with
      gastrojejunostomia. METHODS: We carried out laparoscopic gastric resections in 25
      patients with adenocarcinomas. Our method involved installing five trocars, tying
      the left and right gastric vessels and the right gastro-epiploic vessels,
      sectioning the duodenum 3 cm from the pylorus, sectioning the remaining portion
      of the stomach obliquely 3 cm from the cardias, and performing Billroth II
      reconstruction. RESULTS: The average duration of the operation was 4 h 45 min.
      The average number of removed lymph nodes was 30.5 (range, 22-41). Five patients
      were converted to laparotomy. Significant complications were observed in four
      cases (16%). Hospitalization ranged from 5 to 16 days. The average follow-up was
      38 months (range, 7-63), without evidence of relapse. CONCLUSION: In terms of
      morbidity, our results were similar to those obtained with open surgery.
      Lymphectomy according to the extent and number of lymph nodes is acceptable in
      the treatment of tumors of the lower third of the stomach. More case studies are
      needed to provide further indications of the applicability of the technique
      (which is currently used only in a few centers) and long-term results.

PMID- 11972202
TI  - Direct visual or blind insertion of the primary trocar.
AB  - BACKGROUND: We set out to assess the difference in complication rates between
      primary umbilical insertion by a blind trocar and insertion with an optical
      surgical obturator. METHODS: In a retrospective survey, we investigated the rate
      of severe complications by primary umbilical trocar entry. Of 1546 patients
      undergoing gynecological laparoscopies at a tertiary-care university hospital,
      1000 cases were operated by blind umbilical insertion with a conventional primary
      trocar whereas 546 used an optical primary trocar. RESULTS: The rate of major
      complications during insertion of the primary trocar in the blind insertion group
      was five of 1000 (0.5%), whereas there were no major complications in the optical
      guided insertion group (0.0%). CONCLUSIONS: In comparison with the blind
      insertion of a sharp trocar, optical guidance provides a safe and functional
      primary insertion method that allows to detect adhesions to be detected at an
      early stage, thus preventing injuries to the bowel and abdominal vessels.

PMID- 11972201
TI  - Helium vs carbon dioxide gas insufflation with or without saline lavage during
      laparoscopy.
AB  - BACKGROUND: Helium is an inert gas that, if used for insufflation during
      laparoscopy, may be followed by less postoperative pain than carbon dioxide (CO2)
      insufflation, due to a more limited effect on intraabdominal pH and metabolism.
      Saline lavage has also recently been shown to reduce postoperative pain following
      laparoscopic surgery. To evaluate these possibilities and to better define the
      clinical safety of helium insufflation, we undertook a prospective randomized
      trial comparing CO2 and helium insufflation with or without saline lavage in
      patients undergoing elective laparoscopic upper abdominal surgery. METHODS: From
      January to November 2000, 173 patients undergoing elective laparoscopic
      cholecystectomy or fundoplication were randomized to undergo laparoscopy with
      either CO2 or helium insufflation. Within each group, patients were further
      randomized to undergo peritoneal lavage with 2 L of 0.9% saline at the end of the
      surgical procedure. This yielded the following four patient groups; CO2 (group 1,
      n = 47), CO2 + saline lavage (group 2, n = 43), helium (group 3, n = 43) and
      helium + saline lavage (group 4, n = 40). Patients were blinded to their
      randomization, and post-operative assessment was also performed by a blinded
      investigator, who applied a standardized scoring system to assess postoperative
      pain. RESULTS: The study groups were well matched for age, sex, weight, American
      Society of Anesthesiologists (ASA) status, duration of surgery, and volume of gas
      utilized, and 81% of patients were discharged within 48 h. There were no
      differences in the incidence of postoperative complications among the study
      groups, and postoperative pain scores were not significantly different when all
      four groups were compared. When helium (groups 3 and 4) was compared with CO2
      (groups 1 and 2), no differences in pain score were seen. When no lavage (groups
      1 and 3) was compared with lavage (groups 2 and 4), less pain was found in the
      group undergoing saline peritoneal lavage (mean 4-h pain score, 5.9 vs 5.2; 24-h
      pain score, 4.8 vs 4.1; p > 0.05). CONCLUSIONS: The use of helium insufflation
      for laparoscopic surgery, while not associated with any significant adverse
      sequelae, was not associated with less postoperative pain in this trial. The use
      of saline peritoneal lavage was associated with less pain in the early
      postoperative period.

PMID- 11972203
TI  - Impact of additional pleurodesis in video-assisted thoracoscopic bullectomy for
      primary spontaneous pneumothorax.
AB  - BACKGROUND: Bullectomy for primary spontaneous pneumothorax has been associated
      with high postoperative recurrence rates when video-assisted thoracoscopic
      surgery (VATS) has been used rather than thoracotomy. The aim of this study was
      to evaluate the efficacy and identify the disadvantages, if any, of adding
      pleurodesis to VATS bullectomy to prevent recurrent pneumothorax. METHODS: Fifty
      three patients who underwent VATS bullectomy with additional pleurodesis for
      pneumothorax after November 1996 and 50 who underwent VATS bullectomy alone
      before October 1996 were compared retrospectively in terms of intraoperative
      factors and postoperative chest pain, pulmonary function, and pneumothorax
      recurrent rates. Pleurodesis was achieved by electrocauterizing the upper surface
      of the parietal pleura in a patchy fashion. RESULTS: There were no significant
      differences between the additional pleurodesis group and the bullectomy alone
      group in terms of age, sex, operating time, intraoperative bleeding, number of
      resected bullae, duration of chest drainage, or volume of fluid drained.
      Postoperative chest pain and pulmonary function were also similar in both groups.
      A recurrent pneumothorax occurred in one patient (1.9%) in the additional
      pleurodesis group; this recurrence rate was significantly lower than that for the
      bullectomy alone group (eight patients, 16%; p = 0.029). Although the mean
      postoperative follow-up period was considerably shorter in the additional
      pleurodesis group (38 months [range, 26-49]) than in the bullectomy alone group
      (63 months [range, 50-72] ), eight (89%) of all nine recurrences occurred within
      26 months of surgery-i.e., within the minimum follow-up period for the additional
      pleurodesis group. CONCLUSIONS: Pleurodesis is a minimally invasive technique
      that is effective in preventing postoperative recurrences of pneumothorax when
      added to VATS bullectomy. Additional pleurodesis has no disadvantages vs
      bullectomy alone in terms of worsening postoperative chest pain or pulmonary
      function.

PMID- 11972204
TI  - Assessment of fatigue, monitor placement, and surgical experience during
      simulated laparoscopic surgery.
AB  - BACKGROUND: Laparoscopic surgery requires the surgeon to assume atypical postures
      for extended periods of time, potentially leading to fatigue and chronic injury.
      This study assessed the level of muscle activity and compared the effects of
      fatigue, monitor placement, and surgical experience during simulated laparoscopic
      surgery. METHODS: Four attending and four resident surgeons repeated a series of
      four tasks with a View site and a standard operating room monitor.
      Electromyography (EMG) activity and muscular discomfort scores were obtained
      before and after a "fatigue session." Two variables, the EMG amplitudes and
      discomfort scores, were analyzed. RESULTS: The EMG amplitudes generally exceed
      the recommended threshold limits of acceptable muscular load. EMG data and
      discomfort scores demonstrated a fatigue response in several muscle groups.
      Minimal differences between the two monitor positions were seen. Overall, the EMG
      data and discomfort scores showed less muscle activity and discomfort in the
      attending surgeons. CONCLUSION: Laparoscopic surgery required a relatively high
      muscular load, putting surgeons at risk for fatigue and injury. Altering the
      monitor placement did not reduce the surgeon's risk of fatigue. Experience
      slightly reduced the level of fatigue, but not enough to reduce the surgeon's
      risk category.

PMID- 11972205
TI  - Motion analysis.
AB  - BACKGROUND: The ability to make an objective evaluation of a surgeon's operative
      ability remains an elusive goal. In this study, we used motion analysis as a
      measure of dexterity in the performance of a simulated operation. METHODS:
      Fifteen surgeons performed a total of 45 laboratory-based laparoscopic
      cholecystectomies on a cadaveric porcine liver model. Subjects were assigned to
      one of three groups according to their level of experience in human laparoscopic
      cholecystectomy. Electromagnetic tracking devices were used to analyze the
      surgeon's hand movements as they performed the procedure. Movement data (time,
      distance, number of movements, and speed of movement) were then compared.
      RESULTS: Analysis of variance (ANOVA) movement scores across the three groups
      showed significantly better performance among the experienced laparoscopic
      surgeons than the novices. Learning curves across repetitions of procedures were
      plotted. Novices made more improvement than experts. CONCLUSIONS: Motion analysis
      provides useful data for the assessment of laparoscopic dexterity, and the
      porcine liver model is a valid simulation of the real procedure.

PMID- 11972206
TI  - Clinical applications of plasma shock wave lithotripsy in treating postoperative
      remnant stones impacted in the extra- and intrahepatic bile ducts.
AB  - BACKGROUND: Choledochofiberscopy with basket extraction has been used widely to
      treat postoperative remnant stones in the bile duct system. However, it remains
      difficult to extract stones impacted in the bile duct system or stones too large
      to pass through the T-tube fistula. This report describes the efficacy and safety
      of plasma shock wave lithotripsy (PSWL) in fragmenting and eliminating such
      remnant stones from the bile duct. METHODS: In 52 patients, 117 remnant stones
      were fragmented with PSWL and subsequently extracted with choledochofiberscopy.
      The efficacy and safety of PSWL were observed during and after the procedure.
      RESULTS: After 116 of 117 remnant stones (99.1%) impacted in the extra- and
      intrahepatic bile ducts were fragmented successfulIy with PSWL, they were
      extracted with choledochofiberscopy. There were no significant complications
      during and after the procedure. CONCLUSION: It appears that PSWL is an effective
      and safe method for fragmenting remnant stones impacted in the bile duct system
      and stones too large to pass through the T-tube fistula.

PMID- 11972207
TI  - Laparoscopic lateral L4-L5 disc exposure.
AB  - BACKGROUND: The anterior laparoscopic approach requires precarious dissection
      around the iliac vessels to expose the L4-L5 level. Furthermore, a
      retroperitoneal endoscopic approach to the L4-L5 level requires a technically
      demanding dissection to access the L5-S1 disc space. A unique lateral
      laparoscopic approach to the L4-L5 disc space allows concurrent access to the L5
      S1 space while avoiding major dissection around the iliac vessels. This article
      describes this novel lateral approach and reviews the initial clinical outcomes.
      METHODS: Between January 1999 and April 2000, five patients underwent
      laparoscopic lateral L4-L5 disc exposure at the Cleveland Clinic Foundation. All
      charts were reviewed retrospectively. Mean values +/- standard deviation were
      determined for patient demographics and operative characteristics. A standard
      five-port laparoscopic technique was used. The sigmoid colon was retracted
      medially with an endoloop. The retroperitoneum was entered and the ureter and
      left iliac artery were retracted medially, whereas the psoas was retracted
      laterally. Fluoroscopy delineated the L4-L5 disc space allowing discectomy and
      cage insertion. Postoperatively, subjective patient satisfaction was obtained and
      radiologic evidence of fusion was assessed. RESULTS: All five patients were
      males, with a mean age of 47.4 +/- 7 years and a body mass index of 30 +/- 6
      kg/m2. Four patients had an L4-L5 and L5-S1 fusion and one patient had an L4-L5
      and L3-L4 fusion. Mean operative time was 349 +/- 32 min, with a mean blood loss
      of 210 +/- 74 cc. There were no intraoperative complications and no conversions,
      and postoperatively all patients were started on a clear liquid diet on
      postoperative day 1. The mean length of stay was 3.4 +/- 0.9 days. Patients
      returned to work in a mean of 12 +/- 7 weeks. All patients had evidence of fusion
      on their radiologic follow-up. Four patients were pain free, whereas one patient
      required intermittent narcotics at 1-year follow-up. CONCLUSIONS: For multilevel
      fusions including the L4-L5 disc space, the lateral laparoscopic exposure is a
      safe and efficacious procedure allowing simultaneous access to multiple disc
      spaces while avoiding the sympathetic chain, ureter, and major vascular
      structures. The lateral approach affords excellent exposure for accurate
      deployment of the appropriate orthopedic hardware.

PMID- 11972209
TI  - Ultrasound of the inguinal floor for evaluation of hernias.
AB  - BACKGROUND: This study aimed to evaluate the utility of ultrasound in the
      diagnosis of inguinal hernias and obscure groin pain. METHODS: A series of 65
      consecutive groin explorations performed subsequently to percutaneous ultrasound
      examination were prospectively evaluated. Patients were examined in an office
      setting. The examination included a history and a physical. Then an ultrasound of
      the inguinal region was performed. Ultrasound was performed by the staff surgeon
      and fellows. Patients then were taken to surgery for either a laparoscopic or
      open hernia repair. The preoperative and operative findings were compared to
      determine the utility of groin ultrasound. RESULTS: A series of 41 patients
      presenting with symptoms of groin pain or palpable groin bulge were evaluated
      with ultrasound of the groin. Of these patients, 24 went on to have bilateral
      repairs, bringing the study total to 65 groins. Surgery involved 50 laparoscopic
      and 15 open hernia repairs. This included 20 groins without hernia, as determined
      by physical examination, and 45 groins with a palpable hernia. Overall,
      ultrasound was used to identify the type of hernia correctly (direct vs indirect)
      with 85% success. In the 20 patients who had no palpable bulge, ultrasound
      identified a protrusion (hernia or lipoma) in 17. Two of these were false
      positives, and the three negative ultrasound examinations were false negatives.
      Thus ultrasound identified the pathology in a groin without a palpable bulge at
      an accuracy of 75%. The overall accuracy in finding a hernia of any kind by
      ultrasound was 92%. CONCLUSION: Ultrasound is a useful adjunct in evaluating the
      groin for hernia, and can be performed by surgeons.

PMID- 11972208
TI  - Combined whole tumor cell and monophosphoryl lipid A vaccine improved by
      encapsulation in murine colorectal cancer.
AB  - BACKGROUND: Whole autologous colon cancer vaccines in combination with various
      adjuvants have been used in both animals and humans. At this writing, vaccine
      regimens have been initiated in humans 3 to 6 weeks postoperatively. This delay
      between tumor resection and vaccination gives surviving tumor cells an
      opportunity to establish themselves. Vaccine administered either preoperatively
      or immediately after surgery, in theory, should be more effective. However,
      surgery-related immunosuppression may diminish the effectiveness of pre-operative
      or early postoperative vaccines. This problem may be overcome by limiting
      postoperative immunosuppression via the use of minimally invasive methods.
      Alternatively, the impact of the vaccine may be improved by encapsulating the
      vaccine, plus adjuvant, which in theory, should extend exposure time.
      Encapsulation of cancer vaccines in polysaccharide particles has not yet been
      studied. The goal of this study was to determine whether vaccine encapsulation,
      preoperative vaccination, and early postoperative vaccination affected the tumor
      burden. In addition, laparotomy and carbon dioxide insufflation were compared.
      METHODS: Vaccine was prepared from ultraviolet-irradiated C26 colon cancer cells
      in combination with monophosphoryl lipid A, either in suspension or entrapped in
      alginate beads. The C26 cell line and syngeneic BALB/c mice were used for all the
      studies. Tumor volumes were determined after excision of the tumors 2 weeks after
      inoculation in these studies. RESULTS: Encapsulated vaccine was more effective
      than the standard liquid vaccine. Significantly smaller tumors were noted in mice
      receiving encapsulated vaccine than in either the control group (p <0.01) or the
      liquid vaccine group (p <0.05). The use of a preoperative encapsulated vaccine
      was associated with significantly smaller tumors after laparotomy,
      pneumoperitoneum, or anesthesia alone when the tumors were established
      immediately after surgery. With an already established tumor, encapsulated
      vaccine, when given in the early postoperative period to mice that had undergone
      laparotomy or anesthesia alone was associated with significantly smaller tumors
      that those found in control animals. CONCLUSIONS: The incorporation of a whole
      cell vaccine and monophosphoryl lipid A into alginate beads increases the
      efficacy of pre-operative and early postoperative tumor vaccines in the setting
      of both laparotomy and Carbon dioxide pneumoperitoneum. The use of perioperative
      vaccines may prove to be an effective way to immunize patients with cancer
      undergoing surgery.

PMID- 11972210
TI  - Impact of harmonic scalpel on operative time during video-assisted thyroidectomy.
AB  - BACKGROUND: Minimally invasive video-assisted thyroidectomy (MIVAT) has been
      practiced in our department since 1998. It has some advantages over conventional
      surgery in terms of postoperative pain and cosmetic result. The aim of this study
      was to evaluate the use of the Harmonic scalpel (HS) on the performance of this
      procedure. METHODS: Between October 1998 and January 2001, 116 patients underwent
      MIVAT. The HS was used for the last 26 operations. We compared this group of
      patients (HS-G) with a control group (C-G) of 26 patients who had undergone MIVAT
      before the introduction of the HS. The following parameters were considered: age,
      gender, preoperative diagnosis, size of the lesion, type of operation (lobectomy
      or total thyroidectomy), operative time, complication rate, and postoperative
      hospital stay. RESULTS: The two groups were well matched for age, gender,
      preoperative diagnosis, lesion size, and type of operation. The mean operative
      time was significantly reduced in the HS-G for both lobectomy (37.3 +/- 8.4 vs
      49.4 +/- 18.0 min) and total thyroidectomy (53.8 +/- 16.3 vs 90.6 +/- 22.1 min).
      No differences were found for postoperative stay. One patient in the C-G
      experienced a transient recurrent nerve palsy. There were no other complications.
      CONCLUSIONS: This study showed that the utilization of the HS for MIVAT is safe
      and associated with a shorter operative time. A reduction of the rates for such
      complications such as hypoparathyroidism and recurrent nerve injuries was not
      possible to demonstrate in the present study. Much larger series are needed for
      further evaluation of this instrument.

PMID- 11972211
TI  - Cost comparison of endoscopic stenting vs surgical treatment for unresectable
      cholangiocarcinoma.
AB  - BACKGROUND: Total lifetime costs of endoscopic vs surgical treatment for
      obstructive jaundice due to cholangiocarcinoma are difficult to assess. The
      purpose of this study was to compare total costs in these two groups, including
      all treatment and retreatments. METHODS: This retrospective study identified
      patients with biopsy-proven cholangiocarcinoma treated this decade with either
      endoscopic biliary stenting or surgical biliary-enteric bypass with or without
      resection. Outcomes and hospital charges were recorded. Ten matched control
      patients were compared from each group. Costs included those for cost of repeat
      endoscopy in the endoscopic group and for the management of recurrent obstructive
      jaundice in the surgical group. RESULTS: The groups were similar in age and
      gender ratio. The surgical approach was frequently for cure; therefore, surgical
      patients were by and large at an earlier stage of their disease than those in the
      endoscopic group. Mean survival for the endoscopic group was 19 months vs 16.5
      months for the surgical group. The median total lifetime cost for surgical
      therapy was $60,986 vs $24,251 for endoscopic therapy. CONCLUSION: Endoscopic
      therapy is an effective palliative therapy for unresectable cholangiocarcinoma.
      Endoscopic therapy for this entity costs significantly less than surgical
      treatment. The cost benefit of endoscopic stenting over standard surgical bypass
      in the management of patients with unresectable cholangiocarcinoma, when
      considered along with its minimally invasive approach, makes this the procedure
      of choice for palliative therapy.

PMID- 11972212
TI  - Preoperative chemotherapy unmasks underlying Barrett's mucosa in patients with
      adenocarcinoma of the distal esophagus.
AB  - BACKGROUND: Intestinal metaplasia of the distal esophagus frequently cannot be
      detected in patients with esophageal adenocarcinoma. It has therefore been
      questioned whether Barrett's esophagus is the primary precursor lesion of such
      lesions. We hypothesized that the underlying Barrett's mucosa may be masked by
      tumor overgrowth in the majority of these patients. METHODS: The pretherapeutic
      endoscopy and biopsy records of 79 patients with locally advanced esophageal
      adenocarcinoma who had undergone preoperative chemotherapy were reviewed and
      compared to findings on restaging endoscopy/biopsy and subsequent resection and
      histopathologic analysis of the resected specimen. RESULTS: Pretherapeutic
      endoscopy and biopsy showed associated Barrett's esophagus in 59/79 patients,
      whereas there was no evidence of associated intestinal metaplasia in 20/79
      patients on extensive biopsies. Following neoadjuvant chemotherapy, Barrett's
      mucosa was unmasked and later documented by biopsy or histopathologic assessment
      of the resected specimen in 18 of the latter 20 patients. This resulted in an
      overall association of Barrett's mucosa with adenocarcinoma in the distal
      esophagus of 97.4% CONCLUSION: Underlying Barrett's mucosa is frequently masked
      by tumor overgrowth in patients with locally advanced adenocarcinoma of the
      distal esophagus.

PMID- 11972213
TI  - Evaluation of the usability of two types of image display systems, during
      laparoscopy.
AB  - BACKGROUND: This study was performed to assess the optimal display location of a
      flat-screen monitor for laparoscopy. It was also performed to assess the posture
      (objective), opinion, and preference (subjective) of subjects using a flat-screen
      monitor positioned in the optimal display location and a cathode-ray tube monitor
      on a tower next to the operating table (current situation). METHODS: Twelve
      surgeons performed cholecystectomies using the two display systems alternately.
      The postures of the operator and the assistant were assessed by an infrared video
      analysis system. RESULTS: The posture of the assistant is significantly better
      when using a flat-screen monitor [more neutral head flexions (p = 0.036) and
      neutral neck torsions (p = 0.012)]. No significant differences were found for the
      posture of the operator. The operators and assistants felt more comfortable when
      using a flat-screen monitor (p = 0.008) and they preferred this display to the
      use of a monitor on a tower. CONCLUSIONS: The use of flat-screen monitors is
      better for the physical and psychological comfort of the users, even though the
      technical performance is inferior in comparison with that of regular monitors.

PMID- 11972214
TI  - Thymectomy by thoracoscopic approach in myasthenia gravis.
AB  - BACKGROUND: A series of 25 thoracoscopic thymectomies performed in the Department
      of General Surgery and Liver Transplantation of the Fundeni Clinical Institute
      between April 1999 and April 2000 is analyzed. METHODS: Thoroscopic thymectomies
      were performed on 4 male patients (16%) and 21 female patients (84%), aged
      between 8 and 60 years. RESULTS: The mean operative time was 90 (+/-15) min.
      There were no conversions to open thymectomy. Mortality was nil, and morbidity
      consisted of one minor postoperative right pneumothorax probably related to a
      injury to right mediastinal pleura that was not observed intraoperatively.
      Hospital stay ranged from 2 to 4 days, with a mean of 2.28 days. The patients
      were transferred to the neurological department and they were usually discharged
      after 1 more day. CONCLUSIONS: Postoperatively, all patients had clinical
      improvement of their disease both in symptoms and medication requirements, but a
      longer follow-up is necessary. The results are edifying regarding the very low
      morbidity, the lack of mortality, the acceptance of the patients, and the short
      hospitalization.

PMID- 11972215
TI  - Mechanical ventilation with positive end-expiratory pressure preserves arterial
      oxygenation during prolonged pneumoperitoneum.
AB  - BACKGROUND: Laparoscopic surgery usually requires a pneumoperitoneum by
      insufflating the abdominal cavity with carbon dioxide (CO2). Increased
      intraabdominal pressure causes diaphragmatic displacement resulting in compressed
      lung areas, which leads to formation of atelectasis, especially during mechanical
      ventilation. Application of positive end-expiratory pressure (PEEP) can maintain
      pulmonary gas exchange. The objective of this study was to investigate the effect
      of abdominal gas insufflation on arterial oxygenation during mechanical
      ventilation with and without PEEP in rats. METHODS: In experiment 1, two groups
      of six rats were continuously insufflated with CO2 at 12 mmHg for 180 min. Group
      1 was ventilated with 8 cm H2O PEEP and group 2 had 0 cm H2O PEEP. Group 3 served
      as a control. This group had abdominal wall lifting and was ventilated with 0
      cmH2O PEEP. In experiment 2, two groups of six rats had abdominal CO2
      insufflation and were ventilated with or without PEEP during 180 min (group 4 and
      5). In this experiment, abdomens were desufflated in both groups for 5 min at 60
      and 120 min. Blood pressure monitoring and measurement of arterial pO2 was
      performed by placement of an indwelling carotid artery catheter in both
      experiments. RESULTS: In both experiments, paO2 values decreased significantly in
      insufflation groups that were ventilated with 0 cmH2O PEEP (groups 2 and 5).
      Insufflation groups ventilated with 8 cmH2O PEEP had paO2 values comparable to
      these of control group. There were no significant differences in mean arterial
      pressure between insufflation groups ventilated with or without PEEP. CONCLUSION:
      PEEP preserves arterial oxygenation during prolonged pneumoperitoneum in rats
      with minimal adverse hemodynamic effects.

PMID- 11972216
TI  - Laparoscopic fenestration of posttransplant lymphoceles.
AB  - BACKGROUND: A lymphocele is a common finding after renal transplantation and
      occurs in up to 20% of patients. The majority of patients are asymptomatic.
      However, once a lymphocele has become symptomatic (e.g., through transplant
      dysfunction) this condition has to be treated. We report our 9-year experience
      with laparoscopic lymphocele fenestration and discuss the current management
      options for posttransplant lymphoceles. METHODS: Since 1993, 19 patients (11
      males and 8 females; median age 56 years, range 22-68 years) of a total of 31
      patients with a symptomatic posttransplant lymphocele have undergone laparoscopic
      fenestration of their lymphocele at a median of 66 days (range, 19-111 days)
      following successful renal transplantation in our department. As a first-line
      treatment, a percutaneous pigtail drainage catheter was inserted in all patients.
      In case of failure in resolving the fluid collection, the next step included
      sclerotherapy by instillation of tetracycline or ethanol into the lymphocele
      cavity in some cases. In patients with a persistent lymphocele, a laparoscopic
      lymphocele fenestration via a transabdominal approach was undertaken to achieve
      adequate drainage. RESULTS: Primary laparoscopic lymphocele fenestration was
      successful in all except two patients, who required a conversion. The median
      operating time was 36 min (range, 20-70 min). Following the procedure, renal
      transplant function remained stable or returned to individually normal levels in
      all patients. Median duration of hospital stay was 4 days (range, 1-13 days). At
      median follow-up of 27 months, all patients were alive with a functioning
      transplant. CONCLUSIONS: Laparoscopic lymphocele fenestration is reserved for
      patients in whom temporary drainage with or without sclerotherapy failed to
      resolve the fluid collection. In these cases the laparoscopic approach offers
      obvious technical and clinical advantages compared to open operative techniques.

PMID- 11972217
TI  - A simple technique of laparoscopic port closure allowing wound extension.
AB  - Reliable and safe access to the abdominal cavity and efficient removal of the
      resected gallbladder are essential to laparoscopic cholecystectomy. The
      unpredictable size of the cholecystectomy specimen can sometimes lead to
      frustration at the time of removal. A simple technique has been developed that
      allows for tissue extraction and easy fascial closure regardless of the size of
      the specimen. This is achieved by using a four bite "U-shaped" purse string at
      the time of Hasson insertion, with cephalad advancement of the proximal two
      bites. This allows for variable wound extension and secure closure, without the
      need for additional sutures.

PMID- 11972219
TI  - Laparoscopic distal pancreatectomy. Three cases of insulinoma.
AB  - BACKGROUND: Surgery for benign pancreatic disease has traditionally required a
      major laparotomy however the minimal-access approach is now being applied to a
      wide variety of procedures, and surgery of the pancreas need not be excluded.
      METHODS: Laparoscopic distal pancreatectomy was performed on three patients
      presenting with insulinomas found on preoperative investigation to lie within the
      tail of the pancreas. RESULTS: All three patients had an excellent clinical
      outcome and returned to a state of normoglycemia. All of them made a rapid
      recovery with no major complications. CONCLUSION: Laparoscopic distal
      pancreatectomy is a viable technique for removing insulinoma of the tail of the
      pancreas.

PMID- 11972218
TI  - The laparoscopic option in the management of peritoneal dialysis catheter
      revision.
AB  - BACKGROUND: Long-term functioning of peritoneal dialysis catheters (PDCs) depends
      on maintenance of pelvic positioning and prevention of the formation of
      adhesions. The purpose of this study was to evaluate the validity of laparoscopy
      as a tool for the correction of malfunctioning PDCs and to introduce our
      specially designed technique. METHODS: The charts of 12 patients who underwent
      laparoscopic revisions of malfunctioning PDCs between May 1997 and June 2000 were
      reviewed for perioperative complications and long-term outcomes. We describe the
      causes of malfunction of PDCs and the laparoscopic technique for their revision.
      RESULTS: Of the 12 patients studied, the malfunction of eight catheters resulted
      from migration of the catheter into the upper abdomen. In 4 patients, formation
      of adhesion of either small bowel or omentum resulted in the malfunction of the
      PDC. The only complication we encountered was bleeding. It occurred in 3
      patients, 1 of whom needed reoperation in order to achieve hemostasis. Over a
      median follow-up of 21 months all PDCs treated this way are functioning.
      CONCLUSIONS: The laparoscopic management of malfunctioning PDCs is a valid option
      for the treatment of such a complication.

PMID- 11972220
TI  - Utility of intraoperative endoscopy: implications for surgical education.
AB  - BACKGROUND: The use of intraoperative endoscopy by surgeons can identify
      pathology and help determine the appropriate procedure to perform. However,
      residency training in endoscopy is often variable and unstructured. The purpose
      of this study was to determine the indications for and impact of intraoperative
      endoscopy performed at the time of general surgical procedures. METHODS: The
      records of all patients who underwent intraoperative endoscopy from January 1998
      to December 1999 were reviewed. The indications for endoscopy, endoscopic
      findings, the impact of these findings on the operation performed, complications,
      and whether the patient was spared from undergoing a second procedure on a
      separate date were noted. RESULTS: A total of 107 intraoperative endoscopic
      procedures were performed in 103 patients. Excluding breast, endocrine, central
      line, and peritoneal dialysis catheter cases, endoscopy was utilized in 5.1% of
      all general surgery procedures performed during this time period. In 91 patients
      (88%), the endoscopic procedure was planned preoperatively; in 13 (12%),
      intraoperative findings dictated its use. The most common indications for
      endoscopy were identification of lesions and determination of extent of resection
      (n = 27); evaluation of rectal bleeding (n = 21); colonic evaluation in patients
      with perianal infections (n = 13); evaluation of extent of injury in trauma cases
      (n = 8); evaluation of pain (n = 6); evaluation of intestinal tract hemorrhage (n
      = 6); performance of procedures such as placement of a biliary stent, placement
      of a nasojejunal tube, or polypectomy (n = 5); and surveillance of chronic
      disease (n = 5). In 37 patients (36%), the endoscopic findings affected the
      operation performed. Sixty-nine patients (67%) were spared an endoscopic
      procedure at a second date, which would have required additional sedation or
      anesthesia. There were no complications related to endoscopy. CONCLUSION:
      Intraoperative endoscopy is a valuable tool that can be performed safely for
      multiple indications and is frequently of value in determining the operation to
      be performed. Surgical residents should be trained in the indications for
      endoscopic evaluation as well as the competent performance of such procedures.

PMID- 11972221
TI  - Endoscopic therapy for radiation proctitis-induced hemorrhage in patients with
      prostatic carcinoma using argon plasma coagulator application.
AB  - BACKGROUND: Recurrent hemorrhage in patients with severe radiation proctitis is
      very common. It is often refractory to medical therapy. Endoscopic and surgical
      treatment may be required when conservative medical therapy fails. The aim of
      this study was to assess the therapeutic results of the Argon Plasma Coagulator
      (APC) (ERBE USA, Inc., Marietta, GA, USA) application in patients with radiation
      proctitis-induced hemorrhage. METHODS: Forty patients with radiation-induced
      proctitis causing severe bleeding, who had failed conservative medical management
      were treated endoscopically. Twenty-one patients in this group required blood
      transfusions. RESULTS: APC application was used in 40 patients with only one
      failure. The failed patient underwent formalin application using 4% formalin
      solution with resolution of the bleeding. CONCLUSION: Argon plasma coagulation
      application is a safe, well-tolerated treatment option and, historically, has
      been superior to Nd:YAG laser ablation.

PMID- 11972222
TI  - Digestive hemorrhages of obscure origin.
AB  - BACKGROUND: The diagnosis of digestive bleeding in some cases can require a
      diagnostic laparotomy when other methods have been ineffective. Video-laparoscopy
      can provide such cases with a certain diagnosis and the possibility of performing
      a simultaneous surgical treatment. METHODS: Our experience using video
      laparoscopic to treat digestive hemorrhages of obscure origin involved 16
      patients. The examined patients presented with the following diseases: Meckel's
      diverticulum (8 cases), gastric leiomyoma (1 case), small bowel leiomyoma (4
      cases), jejunum leiomyosarcoma (1 case), small bowel melanoma (1 case), and Peutz
      Jeghers syndrome (1 case). RESULTS: In all these patients the laparoscopic
      approach allowed us to identify the origin and site of the hemorrhages, and
      subsequently to treat the identified lesions. In one patient, an intraperitoneal
      resection of the diverticulum was performed using Endo-Gia (TM30NIF; Tyco Auto
      Suture). In the remaining cases, a minilaparatomy was performed for resection of
      the disordered loop. CONCLUSIONS: Video-laparoscopy is very useful for avoiding
      explorative laparatomies on patients affected by digestive hemorrhages of obscure
      origin. In these cases, the video-laparoscopic approach allows full and
      meticulous explorations of the small bowel to be performed, and seems to be
      useful for diagnosis through direct observation of the lesions. Moreover, if
      necessary, video-laparoscopy can be used for the effective treatment of the
      diseases.

PMID- 11972223
TI  - Delayed cholangitis resulting from a retained T-tube fragment encased within a
      stone: a rare complication.
AB  - Inserting a T-tube after choledochotomy for the removal of bile duct stones
      remains a time-honored practice. Biliary drainage after bile duct exploration has
      some advantages. It minimizes bile leakage, provides access for cholangiography,
      and removes occasional retained stones. The use of T-tubes also has been
      associated with significant complications. Biliary sepsis, bile duct trauma
      during removal, bile leakage leading to peritonitis, retention of a fragment,
      stricture formation after removal have been reported. We report an unusual case
      of cholangitis caused by a T-tube fragment within a large stone, occurring 11
      years after bile duct exploration. A 39-year-old woman underwent common bile duct
      exploration with insertion of a T-tube. Cholangiography was normal, but as the T
      tube was removed, its horizontal limb was missing. The patient failed to present
      for endoscopic removal a few weeks after surgery Five years later, she presented
      with recurrent biliary pains and a mild episode of cholangitis. This last episode
      was associated with severe pain and jaundice. After initial conservative
      treatment, endoscopic retrograde cholangiopancreatography was performed, and
      endoscopic removal of the fragment and stone material was successful. Despite the
      declining numbers of bile duct explorations in the laparoscopic era and the
      tendency to use transcystic drainage or primary closure of a choledochotomy, the
      T-tube will continue to be a useful tool in biliary surgery, subject to
      consideration of the indications and the available alternatives. The reported
      case highlights the importance of careful tube preparation to prevent partial
      separation at removal, and early removal of a missing fragment to avoid potential
      serious complications.

PMID- 11972224
TI  - Intramural pseudodiverticulosis of the esophagus.
AB  - Esophageal intramural pseudodiverticulosis (EIPD) is a rare condition seen in the
      elderly, with a male-to-female ratio of 3:2. Multiple small outpouchings occur in
      the submucosa of the esophageal wall, caused by dilation of the excretory ducts
      of the mucus glands. This disorder may be associated with gastroesophageal
      reflux, motility disorders, candidiasis, or other conditions. Inflammation,
      resulting in periductal fibrosis and compression of the duct orifices, may be a
      causative factor. Usually, EPID presents with progressive dysphagia related to
      esophageal stenosis or strictures in the great majority of patients. Radiologic
      examination is more sensitive than endoscopy in detecting these tiny saccular
      diverticula in the esophageal wall. They often are noted to disappear after
      esophageal dilation, but may persist asymptomatically in some patients. We report
      two cases of dysphagia associated with reflux and Candida infection in elderly
      patients. The diagnosis of EIPD was made, and both patients were treated
      successfully. A review of the available literature suggests that EIPD may be
      missed easily because of subtle endoscopic and radiologic changes, but that once
      diagnosed, conservative management leads to satisfactory control of the symptoms.

PMID- 11972225
TI  - The use of ultrasound to demonstrate small bowel polyps in a patient with Peutz
      Jeghers syndrome.
AB  - A 21-year-old woman presented to the accident and emergency department with a 2
      day history of lower abdominal pain. Her lips had the stigma of melanosis.
      Previously, she had received a diagnosis of Peutz-Jeghers syndrome, although no
      polyps had been detected in small and large bowel barium studies performed
      approximately 8 years before. Clinically, the patient had mild deep lower
      abdominal tenderness, and a mass was palpable in the suprapubic region. Urgent
      ultrasound showed ileoileal intussusception and small polyps in the lumen of the
      small bowel. At laparotomy, ileoileal intussusception was confirmed. It was not
      possible to reduce it because of nonviable small bowel, so 20 cm of the ileum,
      including the intussusception, was excised. After this, intraoperative
      enteroscopy was performed, showing further polyps in the small bowel distal and
      proximal to the intussusception, which were excised locally. Only a few reports
      in the literature describe ultrasound used to diagnose to condition.
      Intraoperative enteroscopy has been recommended as the treatment of choice
      because it allows identification of polyps that previously would have been
      missed.

PMID- 11972226
TI  - Laparoscopic treatment of complications from endoscopic retrograde
      cholangiopancreatography.
AB  - Complications after endoscopic retrograde cholangiopancreatography (ERCP) usually
      are treated endoscopically or by traditional surgical procedure. We present two
      cases of laparoscopic treatment. Patient l had mechanical jaundice. Ultrasound
      scan showed a common bile duct (CBD) extended to 11 mm, and ERCP disclosed a
      stone wedged up in the extrapancreatic part of the CBD. Endoscopic techniques did
      not help to remove the stone, and finally tore off the Dormia basket, leaving it
      in the bile ducts. After unsuccessful attempts at its endoscopic evacuation,
      laparoscopy was performed. A choledochoscope was introduced into the CBD, and the
      Dormia basket was removed. However, the removal of the stone "ingrown" in the
      wall of the CBD was not successful, leading to a laparotomy. Patient 2 had
      cholecysto- and choledocholithiasis. On ERCP, multiple stones filling the CBD
      were found. Combining ECRP with extracorporeal shock-wave lithotripsy,
      sphincterotomy, and mechanical lithotripsy did not lead to removal of all the
      stones, so an endoscopic biliary prosthesis was introduced. During consecutive
      ERCP, one of the prosthetic ends moved into the head of pancreas. Endoscopic
      attempts to remove it were unsuccessful, so laparoscopy was performed. During the
      operation, the CBD was incised, allowing all the remaining stones and the
      prosthetic device to be removed successfully. It seems that laparoscopic
      treatment currently may be an alternative to traditional surgery in the treatment
      of some complications after ERCP.

PMID- 11972227
TI  - "Needlescopic" sigmoid resection.
AB  - Minimally invasive surgical techniques and procedures continue to evolve with the
      trend toward fewer and smaller instruments. To our knowledge, this is the first
      reported case of sigmoid colon resection utilizing needlescopic technology. The
      patient was a 53-year-old woman diagnosed with a malignant lesion in the
      midsigmoid colon at 30 cm. A subsequent needlescopic sigmoid colon resection was
      performed and the patient was discharged home after an uneventful postoperative
      course. This case demonstrates that colon procedures that require major
      reconstruction may be performed needlescopically in selected patients.

PMID- 11972228
TI  - Necrotizing fasciitis with Clostridium perfringens after laparoscopic
      cholecystectomy.
AB  - Necrotizing fasciitis is a rapidly progressive infection of the fascia and
      subcutaneous tissues accompanied by a high mortality rate approaching 80% to
      100%. Factors that predispose patients to this life-threatening complication
      include obesity, malnutrition, malignancy, chronic alcoholism, drug abuse,
      peripheral vascular disease, diabetes mellitus, and immunosuppressive therapy.
      The pathomechanisms for the development of this rare disease still remain
      unclear. We report a case of necrotizing fasciitis with Clostridium perfringens
      after laparoscopic cholecystectomy. The patient left the hospital 5 months after
      admission. Early recognition based on clinical signs (pain, asymmetric abdominal
      thickening, crepitus) and computed tomography scanning (gas dissection along
      fascial planes), in conjunction with prompt, aggressive surgical therapy and
      debridement of all devitalized tissue, high-dose antibiotic therapy, and therapy
      at the intensive care unit, appears to afford patients the best chance of
      survival.

PMID- 11972229
TI  - Benign metastasizing leiomyoma.
AB  - Benign metastasizing leiomyoma is a rare clinical entity that has been described
      in several previous reports. Although the exact pathophysiology of the disease is
      unknown, two predominant theories exist: (1) metastasis from an existing
      leiomyoma (commonly seen with uterine leiomyoma) or (2) multicentric
      leiomyomatous growths rather than actual metastases. We present an interesting
      case in which several elements of the patient's history complicated the
      differential diagnosis.

PMID- 11972230
TI  - Byler disease associated with acute cholecystitis.
AB  - A case of Byler disease, which has a rare incidence of l in 90000, is reported. A
      21-year-old woman known to have the disease since childhood presented with acute
      cholecystitis and underwent laparoscopic cholecystectomy. To the best of our
      knowledge, after a review of the English literature, this is the second patient
      with Byler disease to live beyond the second decade of life since the disorder
      was first described by Clayton 30 years ago, and the first case associated with
      acute cholecystitis that was managed successfully by laparoscopic
      cholecystectomy.

PMID- 11972231
TI  - Endoscopic extraperitoneal repair of a Grynfeltt hernia.
AB  - There are three types of lumbar hernia: congenital, acquired, and incisional
      hernias. Acquired hernia can appear in two forms: the inferior (Petit) type and
      the superior type, first described by Grynfeltt in 1866. We report endoscopic
      extraperitoneal repair of a Grynfeltt hernia. A 46-year-old woman presented with
      a painful swelling in the left lumbar region that had caused her increasing
      discomfort. The diagnosis of Grynfeltt's hernia was made, and she underwent
      surgery. With the patient in a left-side decubitus position, access to the
      extraperitoneal space was gained by inserting a 10-mm inflatable balloon trocar
      just anteriorly to the midaxillary line between the 12th rib and the superior
      iliac crest through a muscle-splitting incision into the extraperitoneal space.
      After the balloon trocar had been removed a blunt-tip trocar was inserted. Using
      two 5-mm trocars, one above and another below the 10-mm port in the midaxillary
      line, the hernia could be reduced. A polypropylene mesh graft was introduced
      through the 10-mm trocar and tacked with spiral tackers. The patient could be
      discharged the next day after requiring only minimal analgesics. At this writing,
      2 (1/2) years after the operation, there is no sign of recurrence. This Grynfeltt
      hernia could safely be treated using the extraperitoneal approach, which obviates
      opening and closing the peritoneum, thereby reducing operative time and possibly
      postoperative complications.

PMID- 11972232
TI  - Splenic cysts: a new approach to partial splenectomy.
AB  - Laparoscopic partial splenectomy of a splenic cyst in a 19-year-old female
      patient is discussed. We successfully performed a laparoscopic partial
      splenectomy and achieved meticulous hemostasis using an Endo-GIA stapling device.
      The patient tolerated the procedure well and was discharged on postoperative day
      2. At this writing, she has been followed for 30 months without cyst recurrence.
      Minimally invasive surgery provides an alternative to conventional surgical
      procedures, with a short hospital stay and without the added morbidity of
      laparotomy.

PMID- 11972233
TI  - Spillage of stones from the gallbladder during laparoscopic cholecystectomy and
      complication of a retroperitoneal abscess mimicking gluteal abscess in elderly
      patients.
AB  - Gallbladder perforation during laparoscopic cholecystectomy with spillage of bile
      and gallstones occurs in a substantial percentage of patients (up to 40%). We
      report the case of a 77-year-old woman who presented with fever of unknown
      etiology and a complication of retroperitoneal abscess mimicking a gluteal
      abscess with gallstones and clips the abscess. Spillage of gallstones from
      perforation of the gallbladder is a well-recognized complication of laparascopic
      cholecystectomy, especially several months after the initial surgery, as in the
      reported case.

PMID- 11972234
TI  - A simple technique for decompression of distended gallbladder during laparoscopic
      cholecystectomy.
AB  - During laparoscopic cholecystectomy, distended gallbladder can create exposure
      difficulties, that precludes adequate visualization, thus rendering laparoscopic
      dissection impossible and even unsafe. To overcome this problems, we devised a
      simple technique for the decompression of distended gallbladders.

PMID- 11972235
TI  - Comparison of laparoscopic and open Nissen fundoplication 2 years after
      operation.

PMID- 11972237
TI  - Unusual trocar site recurrences.

PMID- 11972238
TI  - Comment on a balanced approach to choledocholithiasis.

PMID- 11972242
TI  - Ex vivo repair of a large renal artery aneurysm and associated arteriovenous
      fistula.
AB  - The development of a renal artery to vein arteriovenous fistula due to a large
      extraparenchymal renal artery aneurysm is uncommon. Previous surgical experience
      with this entity is limited. Based on the existing surgical literature,
      nephrectomy has been the treatment of choice. We report preservation of the
      kidney by surgical correction of this entity using ex vivo "bench" repair in a
      middle-aged female with fibromuscular dysplasia of the renal artery. The
      technique, results, and recommendations for surgical management are discussed.

PMID- 11972243
TI  - Endovascular repair of a ruptured abdominal aortic and iliac artery aneurysm with
      an acute iliocaval fistula secondary to lymphoma.
AB  - Abdominal aortic aneurysms (AAA) are common and generally asymptomatic unless
      rupture occurs. A 3 to 4-cm AAA has a 1-2% risk of rupture over 5 years. We
      present the case of an 85-year-old male with a history of chronic lymphocytic
      leukemia, a 3-cm infrarenal AAA, and a 2-cm right common iliac artery aneurysm
      whose AAA ruptured and who developed an acute iliac artery-to-vena cava fistula
      secondary to eroding adenopathy from an aggressive low-grade lymphoma. Initially,
      an open repair was attempted but access to the aorta was not possible because of
      complete encasement of the infrarenal and suprarenal aorta with tumor that was
      clinically invading the aortic wall. Secondary tumor invasion into the aorta is a
      rare complication. An endovascular repair was accomplished with successful
      exclusion of both the aneurysm and the iliocaval fistula. Endovascular repair
      provides a valuable alternative in the "hostile abdomen" when standard open
      repair may be hazardous or impossible.

PMID- 11972244
TI  - Endovascular exclusion of abdominal aortic pathology in patients with concomitant
      malignancy.
AB  - The advent of endoluminal aortic repair has gained increasing popularity as an
      alternative to traditional open surgery in the setting of multiple comorbid
      disease states. This study analyzes a single center experience of excluding
      aortic disease in patients with concomitant malignancy. As part of a Federal Drug
      Administration FDA-approved trial, 318 patients underwent aortic stent-graft
      repair between June 1996 and February 2001. During that period five patients with
      advanced-stage neoplasia were treated. Endovascular management of symptomatic
      abdominal aortic aneurysms (AAA) with a mean diameter of 7.8 cm (range, 6-10 cm),
      was performed in four patients. In the fifth patient, a custom-made aortic
      prosthesis was utilized to exclude a paraanastamotic abdominal aneurysm (PAAA)
      from a previous open AAA repair. Malignancies included esophageal, lung, renal,
      prostate, and urinary bladder cancers. A mean follow-up of 10.1 months was
      available. Successful endoluminal repair was accomplished in all five patients
      with minimal in-hospital morbidity. Mean length of stay was 3.4 days. There were
      no device-related mortalities and no persistent endoleaks detected for the
      duration of follow-up. Aneurysm sac enlargement was not seen in any of the
      patients and complete resolution of the PAAA was noted at one year. Exclusion of
      AAA and other aortic pathology in patients with an associated malignancy can be
      performed with a relatively low procedure-related morbidity and mortality. In
      this population, stent-graft repair remains an individualized option with a
      multidisciplinary team necessary to explore this therapeutic approach.

PMID- 11972246
TI  - The utility of preoperative routine carotid artery duplex scanning in patients
      undergoing aortic valve replacement.
AB  - Patients with aortic valve disease (AVD) typically have a cardiac murmur that
      radiates to the neck and may be indistinguishable from a cervical bruit secondary
      to carotid artery occlusive disease. The purpose of this report was to determine
      the prevalence of significant asymptomatic carotid artery occlusive disease in
      patients undergoing aortic valve replacement (AVR). All patients scheduled for
      AVR were prospectively studied. Preoperative carotid artery color-flow duplex was
      performed in all patients. A total of 204 patients were included in the study and
      significant carotid disease (>50% stenosis of the internal carotid artery) was
      found in 17 (8%). In patients with isolated aortic valve disease, 4/129 (3%) had
      significant stenosis. Of the patients with concurrent aortic valve and coronary
      artery disease, 13/75 (17%) had significant stenosis. The incidence of
      significant carotid stenosis in patients with aortic valve disease was over five
      fold higher in patients with concurrent coronary artery disease (3% vs. 17%, p
      <0.001). The yield of routine carotid duplex scanning for patients undergoing
      isolated AVR is low. However, in the subset of patients with concurrent coronary
      disease, the yield is higher. This finding supports the use of routine carotid
      duplex scanning in patients with coexistent aortic valve and coronary artery
      disease.

PMID- 11972245
TI  - Nonoperative management of acute spontaneous renal artery dissection.
AB  - Isolated spontaneous renal artery dissection is a rare condition that can result
      in renal parenchymal loss and severe hypertension. Although several risk factors
      have been identified in association with renal artery dissection, the natural
      history is not well defined. The rarity and nonspecific presentation of the
      disease often lead to diagnostic delay. That, coupled with the anatomic
      limitations imposed by dissection into small branch arteries, frequently
      precludes successful revascularization. Over a 12-month period, four cases of
      spontaneous renal artery dissection (SRAD) were treated at a single institution.
      The patients (ages 44-58 years) presented with acute onset of abdominal/flank
      pain, fever, and hematuria. Diagnostic work-up included an abdominal CT scan
      revealing segmental renal infarction. Angiographic evaluation was diagnostic for
      renal artery dissection in all cases. In one case there was evidence of
      fibromuscular dysplasia (FMD), and in a second there was acute dissection
      superimposed upon atherosclerotic disease. Diagnosis was made within 12-72 hr of
      the onset of symptoms. All patients were managed expectantly with
      anticoagulation. Two patients were known to have a history of hypertension prior
      to admission. All four patients have required antihypertensive treatment
      following dissection, but the condition has been easily controlled. Renal
      function has remained stable in all cases. None of the four cases required
      exploration. Two of the four patients underwent repeat angiographic evaluation
      for recurrent symptoms of pain. In the case of the patient with FMD, a new
      dissection was seen in the contralateral renal artery, and in the second, repeat
      angiogram revealed proximal remodeling of the dissected artery. Management
      strategies for SRAD include surgical revascularization, endovascular
      intervention, and observation with or without anticoagulation. The available
      literature does not demonstrate a clear benefit of treatment with any of these
      modalities. In the short term, the combination of anticoagulation and expectant
      management appears to produce satisfactory outcomes for this difficult problem.

PMID- 11972247
TI  - Surgical management of acute complications and critical restenosis following
      carotid artery stenting.
AB  - Carotid artery angioplasty with stenting (CAS) is being increasingly used in the
      treatment of extracranial carotid artery stenosis. As in other catheter-based
      approaches to the treatment of arterial disease, surgical intervention may be
      required because of either acute complications or correct critical restenosis. We
      have reviewed our experience managing early complications and critical in-stent
      restenoses after CAS in a tertiary care university hospital and a Veterans
      Affairs Medical Center. During the last 5 years, 22 carotid arteries (21
      patients) underwent CAS. One patient developed thrombosis and rupture of the
      carotid artery during stenting. Two other patients (3 arteries) developed
      critical restenosis within 12 months. Subsequent surgical reconstructions
      included an internal carotid artery (ICA)-to-external carotid artery (ECA)
      transposition and a common carotid artery (CCA)-to-ICA bypass with reversed
      saphenous vein (RSV). The patient who underwent CCA-to-ICA bypass later required
      subclavian-to-ICA bypass because of rapidly progressive intimal hyperplasia and
      subsequent occlusion of the CCA. The other patient has not had surgical repair
      because of his deteriorating condition and significant co-morbidities. During the
      same time period, two additional patients were referred from outside institutions
      specifically for surgical intervention after carotid stenting. One had delayed
      rupture of the carotid artery 1 day after stenting and underwent urgent surgical
      repair. Another patient had early, critical restenosis within the stent and
      underwent placement of a CCA-to-ICA interposition graft using RSV. Acute
      treatment failures after CAS can be successfully managed using standard surgical
      techniques. Patients who develop critical in-stent restenosis requiring surgical
      repair may need more challenging surgical reconstructions to maintain cerebral
      perfusion.

PMID- 11972248
TI  - The safety of carotid endarterectomy in patients with preoperative renal
      dysfunction.
AB  - Recent published data suggest that performing carotid endarterectomy (CEA) in
      patients with renal dysfunction is associated with a prohibitively high
      perioperative stroke and death rate. On the basis of our experience, we
      hypothesized that CEA is a safe procedure in patients with renal insufficiency. A
      retrospective review of one surgeon's CEA experience from 1988 to 1998 was
      performed. A total of 398 procedures performed on 370 patients were reviewed for
      patient demographics and adverse events in the 30-day perioperative period. Risk
      factors, indications for procedure, and degree of stenosis, as well as
      intraoperative use of shunts, patch angioplasty, drains, completion angiography,
      and EEG monitoring were compared. Patients were categorized by preoperative
      creatinine (Cr) levels as normal (Cr <or= 1.5) or abnormal (Cr > 1.5). All data
      were subjected to statistical analysis. Our results showed that CEA can be
      performed safely in patients with renal dysfunction with no increase in
      perioperative stroke or death rate. Performing CEA in patients with renal
      insufficiency does require preoperative cardiac evaluation and close cardiac
      monitoring, as there appears to be an increased rate of myocardial infarction in
      our series.

PMID- 11972250
TI  - Initial experience with dorsal venous arch arterialization for limb salvage.
AB  - Surgical reconstruction for patients with symptomatic lower extremity arterial
      occlusive disease is successful when a suitable distal target vessel is present.
      In patients with unreconstructable disease, practical surgical options are at a
      minimum. We report our initial experience with dorsal venous arch arterialization
      (DVAA) for limb salvage. Patients with a lower extremity arteriogram and
      tibia/plantar artery duplex scan demonstrating unreconstructable occlusive
      disease were evaluated for DVAA. The venous arch valve lysis technique consisted
      of retrograde balloon catheter, arterial dilator disruption, and direct
      valvulectomy. Outcome variables included patency, limb salvage rate, and toe
      pressure alterations. Initial results suggest that DVAA may be a viable option
      for end-stage limb salvage. Application of the DVAA appears to be more suitable
      for patients with symptoms secondary to atherosclerosis than those with Buerger's
      disease.

PMID- 11972249
TI  - Early experience using the Wallgraft in the management of distal microembolism
      from common iliac artery patholology.
AB  - Blue toe syndrome commonly occurs as a result of aneurysmal or atherosclerotic
      disease in the iliac arteries. Surgery, angioplasty, or intraarterial stent
      placement are the most common treatment options but the optimal management has
      not been defined. Here we report managing distal microembolization from iliac
      artery atherosclerosis associated with aneurysmal dilation with the Wallgraft
      Endoprosthesis, a self-expanding metallic stent covered with Dacron. Three common
      iliac arteries in two patients were treated using this device. A 79-year-old male
      presented with unilateral symptoms and an 83-year-old female with bilateral
      disease. Arteriography demonstrated complex plaque at the aortic bifurcation
      associated with aneurysmal dilation of the distal common iliac artery in both
      patients. This complex disease was successfully covered using the Wallgraft
      Endoprosthesis. Postoperatively the patients received aspirin, their toe lesions
      healed, and neither has had a recurrence after 16 months. Covered stents offer
      the theoretic advantage of completely excluding the diseased segment, preventing
      the escape of thrombus or plaque debris, and covering aneurysmal dilation in the
      artery.

PMID- 11972251
TI  - Delayed retroperitoneal arterial hemorrhage after inferior vena cava (IVC) filter
      insertion: case report and literature review of caval perforations by IVC
      filters.
AB  - Transvenous placement of inferior vena cava (IVC) filters has become commonplace
      in selected patients with deep venous thrombosis (DVT) and pulmonary embolism
      (PE). IVC filters have been shown to have excellent therapeutic efficacy and low
      complication rates. Penetration of the IVC by filter hooks or struts has been
      reported and commonly noted to be inconsequential. We report a laceration of a
      lumbar artery by a stainless steel Greenfield (SSG) filter strut that resulted in
      a near fatal hemorrhage, and review the world literature on caval perforation by
      IVC filters.

PMID- 11972252
TI  - Does surgical intervention significantly prolong the patency of failed
      angioaccess grafts previously treated with percutaneous techniques?
AB  - In the last decade, percutaneous techniques have been increasingly used to treat
      angioaccess graft thrombosis. Often when catheter-based treatment fails, surgeons
      are called upon to treat these occluded bridge fistulas. It has been our
      impression that operative intervention has not significantly increased the
      longevity of angioaccess grafts that have failed percutaneous intervention.
      During a 2-year period, 101 operative procedures were performed on failed bridge
      fistulas. All had previously been treated with percutaneous thrombolysis and
      dilatation. The number of previous interventions ranged from one to five. Primary
      patency rates of the angioaccess grafts following surgical revision were 43%,
      24%, and 12% at 30, 60, and 90 days, respectively. We conclude that surgical
      intervention does not significantly prolong the patency of angioaccess grafts
      that have previously failed percutaneous interventions and that its routine use
      cannot be recommended.

PMID- 11972253
TI  - Postoperative regression of retroperitoneal fibrosis in patients with
      inflammatory abdominal aortic aneurysms: evaluation with spiral computed
      tomography.
AB  - Partial or total regression of aortic and retroperitonel fibrosis after surgery
      has been reported in combination with inflammatory abdominal aortic aneurysm
      (AAA). In this report, we consider the most recent 21 patients with inflammatory
      AAA consecutively operated on at our institution. The group was composed of 19
      men and 2 women, with a mean age of 66 years. In addition to preoperative CT
      angiographic study, abdominal ultrasound and aortoiliac angiography were also
      performed. There were no perioperative deaths. The perioperative morbidity rate
      was 9.5%. In 20 cases (95.2%), the aortic wall was subjected to histological
      examination with calculation of an inflammatory index. Each patient was
      reexamined with spiral CT angiography after surgery; postoperative results were
      assessed in terms of changes in maximal fibrotic-mantle thickness observed on
      follow-up spiral CT angiograms, expressed both in millimeters and percentage of
      change. Regression was analyzed for possible correlation with preoperative
      severity of fibrotic reaction, time of the postoperative exam, inflammatory
      index, and changes in the fibrotic process involving the adjacent structures. The
      results show that postoperative improvement was significantly more marked in
      cases characterized by higher preoperative inflammatory indices in the aneurysmal
      wall; the time course of regression was highly variable; but on the whole,
      improvement was more substantial during the early months after surgery, with
      significant slowing after the second or third year.

PMID- 11972254
TI  - Infrainguinal endovascular and bypass surgery for critical leg ischemia in
      patients on long-term dialysis.
AB  - Lower limb revascularization has been shown to be worthwhile for treatment of
      critical leg ischemia in uremic patients, but poor results are expected in
      patients on long-term dialysis. We have retrospectively evaluated the results of
      a series of 21 consecutive patients on long-term dialysis who underwent 20
      infrainguinal bypass graft and 5 endovascular procedures for critical leg
      ischemia to identify factors contraindicating any infrainguinal revascularization
      attempt in this patient population. At 2-year follow-up, the patency rate was
      74%, leg salvage rate was 85%, and survival rate was 23%, whereas 23% of patients
      were alive with salvaged leg. Patients on hemodialysis achieved better survival
      outcome than patients on peritoneal dialysis (p = 0.02). Multivariate analysis
      showed that low serum level of albumin (p = 0.009; p = 0.005) and coronary artery
      disease (p = 0.0002; p = 0.001) had an adverse effect on the survival rate and on
      the rate of patients alive with salvaged leg, respectively. Patients without
      coronary artery disease achieved an alive-with-salvaged-leg rate at 1- and 2-year
      follow-up of 68% and 41%, respectively, whereas 12% of patients with coronary
      artery disease survived with salvaged leg after 1 year, but none of them survived
      with salvaged leg at 2-year follow-up (p = 0.003). In conclusion, infrainguinal
      revascularization for lower extremity ischemia in dialysis patients is hardly
      indicated in the presence of coronary artery disease and severe hypoalbuminemia.

PMID- 11972255
TI  - Combined infrarenal aorta and carotid artery reconstruction: early and late
      outcome in 152 patients.
AB  - Between January 1, 1985 and December 31, 1998, we performed combined infrarenal
      aorta and carotid artery reconstruction in 152 consecutive patients. The mean age
      of these patients was 65.4 +/- 8.6 years (range, 43-88 years). Infrarenal aortic
      disease involved abdominal aortic aneurysm in 78 patients (44.7%) and occlusive
      aortoiliac lesions in 84 (55.3%). Carotid artery disease was detected by
      performing routine Doppler ultrasonography prior to aortic reconstruction. A
      total of 121 carotid lesions were asymptomatic (79.6%). A total of 32 patients
      (21%) had a history of contralateral carotid repair. Eighty-one patients (53.2%)
      presented with coronary artery disease diagnosed on the basis of clinical and/or
      laboratory testing. Concurrent lesions were diagnosed in the renal arteries of 43
      patients (28.3%) and in the visceral arteries of 16 (10.5%). Based on the results
      of cardiac evaluation, eight patients underwent coronary revascularization before
      combined reconstruction. Renal or visceral artery reconstruction was carried out
      during the same procedure in 30 (19.7%) and 10 (6.6%) patients, respectively.
      Univariate analysis demonstrated six factors that were significantly associated
      with perioperative mortality and morbidity: age, coronary artery disease, chronic
      obstructive pulmonary disease, procedure time, intraoperative blood loss, and
      creatinemia over 140 micromol/L. Multivariate analysis showed that only the first
      four of these factors were independent. Actuarial survival in the overall
      population, including the patients who died during the perioperative period, was
      73.9 +/- 7.1% at 5 years and 50.9 +/- 10% at 10 years. From our experience, we
      conclude that combined infrarenal aorta and carotid artery reconstruction can be
      performed with no additional operative risks and consequently is the strategy of
      choice. In our series neither procedure had any effect on the early or late
      outcome of the other. Our experience suggests that combined surgery is a safe
      alternative to staged surgery in patients with concurrent lesions involving the
      infrarenal aorta and carotid artery bifurcation.

PMID- 11972256
TI  - Stent graft of abdominal aortic aneurysm after renal transplantation.
AB  - The necessity of operative treatment of abdominal aortic aneurysm (AAA) is
      reported in an increasing number of patients after renal transplantation as a
      result of improved renal graft long-term survival. In these patients, aortic
      surgery however, places the allograft at risk for ischemic damage. We present a
      first case of AAA stenting in a kidney-grafted patient. This procedure helped us
      avoid ischemia of the graft, which showed excellent function pre- and
      postoperatively. The patient had an uneventful recovery with no evidence of renal
      dysfunction and was discharged in good condition 7 days after stenting. This case
      demonstrates a useful alternative for the repair of AAA in kidney-grafted
      patients.

PMID- 11972257
TI  - Atheroemboli to superior mesenteric artery following cardiopulmonary bypass.
AB  - Intestinal ischemia after open heart surgery is an uncommon but often fatal
      complication. The ischemia is generally seen in the context of a low-flow state,
      and less frequently is associated with an occlusion in the mesenteric
      circulation. We report a case of intestinal ischemia caused by an atheroemboli in
      a patient who had an intraaortic balloon pump (IABP) placed during a coronary
      artery bypass graft (CABG).

PMID- 11972258
TI  - Anomalous origins of the right vertebral, subclavian, and common carotid arteries
      in a patient with a four-vessel aortic arch.
AB  - Many anomalies of the aortic arch and great vessels are uncovered as
      serendipitous findings on imaging studies, in the anatomy laboratory, or at
      surgery. A 56-year-old man had an arch angiogram as part of an evaluation for
      cerebrovascular disease. A four-vessel left aortic arch was identified consisting
      of the right carotid, left carotid, right subclavian, and left subclavian
      arteries. The right common carotid gave rise to the right vertebral artery in the
      chest while the normally located left vertebral arose from the left subclavian
      artery. No aneurysm or aortic diverticulum was identified.

PMID- 11972259
TI  - Superior mesenteric artery-to-renal artery bypass: a rare but useful alternative
      for renal artery revascularization.
AB  - The aorta, celiac axis, and iliac arteries are the most common inflow arteries
      used for renal revascularization. When these inflow vessels are diseased, the
      superior mesenteric artery (SMA) can be an alternative source of renal artery
      graft inflow. Previous reports have suggested that only an enlarged SMA should be
      used for this purpose, for fear of developing mesenteric ischemia. We report a
      patient who required renal artery revascularization with a saphenous vein graft
      from a normal-caliber SMA who did not develop subsequent mesenteric ischemia. The
      procedure was unique in demonstrating that the SMA can be used as a viable source
      of graft inflow even when it is anatomically normal.

PMID- 11972261
TI  - Primary aortoenteric fistula: pitfalls in the diagnosis of a rare condition.
AB  - Primary aortoenteric fistula is such a rare condition that even specialist
      vascular surgeons may not encounter one in their lifetime practice. Any hope of
      survival depends upon prompt diagnosis and surgical treatment. We present our
      experience of one such case, particularly the difficulties encountered in
      confirming the diagnosis, and go on to review the literature on the subject. Both
      our experience and that reported by previous authors would suggest that
      specialized investigations such as computed tomography, contrast angiography,
      radionuclide scintigraphy, and gastrointestinal endoscopy have only a limited
      contribution to make in confirming the diagnosis of primary aortoenteric fistula.
      The diagnosis should be considered in any patient with gastrointestinal blood
      loss and an abdominal aortic aneurysm. Specialized investigations should not be
      relied upon to confirm or refute the diagnosis. Any prospect of survival is
      dependant upon prompt diagnosis and surgical intervention. The latter is only
      achieved by a high index of clinical suspicion.

PMID- 11972260
TI  - Venous aneurysm following construction of a polytetrafluoroethylene arteriovenous
      dialysis graft.
AB  - Expanded polytetrafluoroethylene (ePTFE) is the most commonly employed vascular
      prosthetic for constructing arteriovenous fistulas for hemodialysis. Venous
      aneurysm is a rare complication following construction of such fistulas. We
      describe the case of a saccular aneurysm of the cephalic vein arising after
      construction of a PTFE arteriovenous graft for hemodialysis. The aneurysm was
      successfully resected with primary repair of the vein, allowing continued use of
      the graft for dialysis.

PMID- 11972262
TI  - The role of platelets in peripheral arterial disease: therapeutic implications.
AB  - Peripheral arterial disease (PAD) is associated with platelet hyperaggregability
      as well as an increase in morbidity and mortality from myocardial infarction and
      stroke. Enhanced platelet activation in PAD may substantially contribute to these
      adverse outcomes. A relative resistance to aspirin therapy has been reported in
      patients with PAD. Therefore, clopidogrel may be superior to aspirin in treatment
      of PAD. Furthermore, the aspirin + clopidogrel combination could be more
      effective than monotherapy but its risk-benefit ratio has yet to be evaluated.
      Clopidogrel is preferable to ticlopidine because of its safer profile and the
      convenience of once-daily administration. The glycoprotein (Gp) IIb/IIIa
      inhibitors may also find a place as short-term therapy after peripheral
      angioplasty. There is a need to consider the use of clopidogrel in patients who
      cannot tolerate aspirin. Patients who have an event while taking aspirin also
      present a problem. One possibility here is to substitute aspirin with clopidogrel
      or to add clopidogrel to the aspirin. Although these options are currently not
      evidence based in patients with PAD, there is emerging evidence showing that they
      are realistic choices.

PMID- 11972265
TI  - Long-term outcome of patients with gastrointestinal bleeding of obscure origin
      explored by push enteroscopy.
AB  - BACKGROUND AND STUDY AIMS: Little is known of the long-term outcome in patients
      with gastrointestinal bleeding of obscure origin, who undergo investigation by
      means of push enteroscopy. The aim of this study was to assess the rate of
      recurrent bleeding and its predictive factors in patients with gastrointestinal
      bleeding of obscure origin, after exploration by push enteroscopy. PATIENTS AND
      METHODS: 105 patients with gastrointestinal bleeding of obscure origin (iron
      deficiency anemia: n = 56; overt bleeding: n = 49) underwent exploration by push
      enteroscopy from December 1994 to December 1998. They were classified into three
      groups according to enteroscopy findings: no lesion found (group A; 56 patients),
      arteriovenous malformations (group B; 18 patients), and other gastrointestinal
      lesions (group C; 31 patients). Actuarial rates of rebleeding during follow-up
      were calculated and factors associated with rebleeding were assessed by means of
      univariate and multivariate analysis. RESULTS: Follow-up data were obtained for
      101 patients (96 %). The mean follow-up was 29 months (6 - 54 months). The 2-year
      actuarial rate of rebleeding was 31 % in the overall population, and 27.6 %, 56 %
      and 24 % in groups A, B, and C, respectively (P = 0.13). The number of previous
      bleeding episodes and the number of packed red cell units transfused were two
      independent factors predictive of recurrent bleeding. The modality of recurrent
      bleeding (anemia or overt bleeding) was similar to that of the initial episode in
      94 % of cases. In group A, a gastrointestinal lesion was found after rebleeding
      in one of the 12 patients with iron-deficiency anemia, and in four of the five
      patients with overt bleeding. CONCLUSION: Recurrent bleeding occurs in about one
      third of patients who undergo investigation by push enteroscopy for
      gastrointestinal bleeding of obscure origin, with a trend towards more frequent
      rebleeding in patients with arteriovenous malformations. Frequent previous
      bleeding episodes and transfusion requirements are predictive of recurrent
      bleeding.

PMID- 11972266
TI  - Do explicit appropriateness criteria enhance the diagnostic yield of colonoscopy?
AB  - BACKGROUND AND STUDY AIMS: Appropriateness of use of colonoscopy is an important
      issue in health care in the quest to improve quality of care while at the same
      time containing costs. This prospective study examined whether detailed and
      explicit appropriateness criteria significantly improve the diagnostic yield of
      colonoscopy. PATIENTS AND METHODS: Consecutive patients referred for diagnostic
      colonoscopy at five centers (one university hospital and its outpatient
      department, two district hospitals, and two gastroenterology practices) were
      prospectively studied over a 17-month period. The appropriateness of the
      indications for these colonoscopies was assessed using explicit Swiss criteria
      developed by the Rand Corporation/University of California at Los Angeles
      (RAND/UCLA) panel method, and the relationship between appropriateness of use and
      the presence of clinically relevant endoscopic lesions was analysed. RESULTS:
      1188 patients were included in the study. Indications for 1144 (96.3 %) of the
      colonoscopies could be evaluated using explicit criteria; 64.1 % of the
      colonoscopies were judged appropriate, 13.3 % uncertain and 22.6 % inappropriate.
      Significant endoscopic lesions were found in 23.8 % of the colonoscopies.
      Colonoscopies judged appropriate or uncertain yielded significantly more relevant
      lesions than did those judged to be inappropriate (25.6 % vs. 17.4 %; P = 0.007).
      Of 51 colon cancers, all but one were found in colonoscopies judged to be
      appropriate or uncertain. In a multivariate analysis, the diagnostic yield of
      colonoscopy was significantly influenced by appropriateness, patient gender and
      treatment setting. CONCLUSIONS: The use of detailed and explicit appropriateness
      criteria for colonoscopy significantly enhances the identification of relevant
      lesions and in particular of colon cancer. The use of such criteria could
      therefore improve patient selection for colonoscopy and thus contribute to
      efforts aimed at enhancing the quality and efficiency of care.

PMID- 11972267
TI  - Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture
      of superficial esophageal carcinoma.
AB  - BACKGROUND AND STUDY AIMS: In this study we clarify the microvascular
      architecture of superficial esophageal carcinoma as observed by ultra-high
      magnification endoscopy and stereoscopic microscopy with Microfil injection.
      PATIENTS AND METHODS: We observed two surgically resected specimens of
      superficial esophageal cancer under stereoscopic microscopy with Microfil
      injection. In addition, in the histological investigation, we measured the
      caliber of the vessels at the surface of the tumor. We carried out ultra-high
      magnification before treatment in 82 patients with superficial esophageal
      neoplasms. We classified the depth of tumor penetration of superficial esophageal
      carcinoma into four categories: m1 to m3 (mucosal cancer) and sm (submucosal
      cancer). RESULTS: By observing the normal esophageal mucosa under a stereoscopic
      microscope and an ultra-high magnification endoscope, we were able to visualize
      the intrapapillary capillary loops (IPCL). In cancer lesions, we observed
      characteristic changes in the superficial microvascular architecture according to
      the depth of tumor invasion. In m1 invasion, there was dilatation of the IPCL; in
      m2 invasion, there was dilatation and elongation of the IPCL; in m3, there was a
      mixed appearance of the IPCL and tumor vessels; and in sm invasion, complete
      replacement by tumor vessels. On the basis of the above criteria, ultra-high
      magnification endoscopic observation before treatment showed a rate of agreement
      between histological depth of invasion and magnified appearance of 60/72 cases
      (83.3 %) for which satisfactory pictures were obtained. The histological
      investigation showed the caliber of the IPCL of the m1 cancer lesions (12.9 +/-
      3.9 microm) to be significantly greater than that of the normal esophageal mucosa
      (6.9 +/- 1.5 microm) (P < 0.0001). CONCLUSIONS: Observation of the microvascular
      architecture of superficial esophageal carcinoma is useful in the diagnosis of
      the depth of invasion.

PMID- 11972268
TI  - Comparison between magnifying endoscopy and histological, culture and urease test
      findings from the gastric mucosa of the corpus.
AB  - BACKGROUND AND STUDY AIMS: The incidence of Helicobacter pylori infection in
      Japan is high. Unlike the case in Western countries, H. pylori-induced gastritis
      in Japanese patients has a tendency to spread to the corpus. H. pylori-induced
      gastritis is characterized by a number of specific endoscopic findings. In a
      previous study, the endoscopic features and a magnified view of the gastric
      mucosa of the corpus of H. pylori-negative normal stomach were described. This
      report describes the specific histological features and magnified views of the H.
      pylori-negative stomach and compares them with those seen during H. pylori
      induced gastritis. PATIENTS AND METHODS: The anterior wall or greater curvature
      of the middle body of the stomachs of 297 patients were observed by magnifying
      endoscopy (x 80). Forceps biopsy was performed at the following locations: i) the
      magnified site, for histological examination; ii) the antral mucosa, for
      culture/urease test, and histology; and iii) greater curvature of the upper body
      for culture/urease test. RESULTS: 72 patients were diagnosed as having H. pylori
      negative normal stomach and 225 as having H. pylori-positive gastritis. The
      magnified views were classified into four types: i) collecting venules, with true
      capillaries forming a network, and gastric pits resembling pinholes (type Z-0; n
      = 80); ii) irregular true capillaries but no collecting venules observed (type Z
      1; n = 36); iii) white gastric pits and sulci, with neither collecting venules
      nor true capillaries being seen (Z-2; n = 110); and iv) dilated pits with
      surrounding redness (Z-3; n = 71). All cases of H. pylori-negative normal stomach
      were type Z-0, whereas H. pylori-induced gastritis was present in all cases where
      the classification was Z-1, Z-2, or Z-3. Type Z-0 differed significantly from
      types Z-1, Z-2, and Z-3 with regard to the grade of inflammation, activity, and
      presence of H. pylori. CONCLUSIONS: Collecting venules and true capillaries
      forming a network with gastric pits in the center (type Z-0) were observed in the
      H. pylori-negative normal mucosa. The magnified views of H. pylori-related
      gastritis clearly differed from type Z-0.

PMID- 11972269
TI  - Novel three-channel and three-slit stiffening tube for total colonoscopy.
AB  - BACKGROUND AND STUDY AIMS: Because of the recent marked reduction in the diameter
      of colonoscopes, existing stiffening tubes require modification of their tips and
      hardness. The aim of this study was to develop a new stiffening device with a
      flexible soft tip which closely fitted the colonoscope. It was also designed with
      three slits, to improve the fit of the stiffening tube itself to the colonoscope
      and to extend the effective colonoscope length, and equipped with three channels
      for endoscopic treatment. MATERIALS AND METHODS: The standard stiffening tube
      which has been used routinely and a novel three-channel, three-slit (TCTS)
      stiffening tube were employed alternately (in 160 and 161 patients,
      respectively). The two tubes were compared for severity of pain experienced by
      patients, ease of intubation, and complications. RESULTS: Among the 160 patients
      examined with the standard stiffening tube, one (0.63 %) complained of mild anal
      pain on intubation and intubation was incomplete in two (1.25 %), because of
      resistance in the rectum and sigmoid colon. Among the 161 patients examined with
      the TCTS stiffening tube, three patients who presented early in the series (1.86
      %) developed mild proctal redness and erosions, but incomplete intubation or
      serious complications were not recorded. CONCLUSION: The TCTS stiffening tube was
      as easy to use as the standard stiffening tube, and is considered to be both safe
      and useful.

PMID- 11972270
TI  - Routine use of transrectal ultrasound in rectal carcinoma: results of a
      prospective multicenter study.
AB  - BACKGROUND AND STUDY AIMS: Preoperative transrectal ultrasound (TRUS) can
      establish the depth of penetration of a tumor, and thus provide important
      information for decisions about further management. In the literature, this
      method is reported to have a high level of sensitivity and specificity. Our
      investigation aimed at establishing the quality of the diagnostic procedure and
      treatment of colorectal carcinoma. PATIENTS AND METHODS: This investigation,
      which covered a 1-year period, and involved 75 hospitals, was conducted in the
      form of a prospective multicenter study and included a total of 3756 patients.
      For rectal carcinomas, all endosonographically determined uT categories were
      compared with histologically established T categories (pT). RESULTS: At 49
      hospitals a total of 499 TRUS examinations in 1463 rectal carcinomas (34.1 %)
      were performed. A comparison of uT with pT category was possible for 422 TRUS
      examinations. Agreement between the preoperative endosonographic diagnosis with
      the histological diagnosis was found in 63.3 % (n = 267) of cases (95 %
      confidence interval 58.5 % - 67.9 %). The diagnostic accuracy was 50.8 % for pT1
      carcinomas, 58.3 % for pT2 lesions, 73.5 % for pT3 tumors, and 44.4 % for pT4
      carcinomas. Overstaging was observed in 23.9 %, overall, and understaging in 12.8
      %. Understaging was significantly less common than overstaging (P < 0.05, s.).
      CONCLUSION: The accuracy of transrectal ultrasound used as a routine clinical
      examination in rectal carcinoma patients was clearly lower than that reported in
      the literature. We conclude that TRUS may aid decisions relevant to treatment
      only when used by well-trained investigators with a large case load of rectal
      carcinoma patients. Centralization of transrectal ultrasonography service is
      mandatory if a high level of quality is to be achieved with this method.

PMID- 11972271
TI  - Diagnosis of gastroesophageal varices and portal collateral venous abnormalities
      by endosonography in cirrhotic patients.
AB  - BACKGROUND AND STUDY AIMS: The role of endosonography (EUS) in the management of
      portal hypertension is not well defined. We aimed to study the use of a new
      generation video-echo endoscope in the diagnosis of gastroesophageal varices
      (GEV) and extraluminal venous abnormalities in cirrhotic patients. PATIENTS AND
      METHODS: Cirrhotic patients were studied by echo endoscopy to assess esophageal
      varices endoscopically, and gastric varices and extraluminal venous abnormalities
      sonographically. The results were compared with esophagogastroduodenoscopy (EGD)
      examination. Dyspeptic patients served as controls. RESULTS: A total of 52
      cirrhotic and 166 dyspeptic patients were studied. EUS identified esophageal
      varices (EV) endoscopically in 28 patients (53.8 %), which showed a good
      correlation with EGD findings (r = 0.855, P < 0.001). The red color sign and
      portal hypertensive gastropathy were diagnosed in six and seven patients,
      respectively, by both methods. EUS detected gastric varices sonographically in 16
      patients (30.8 %), compared with detection in nine patients by EGD. Extraluminal
      venous abnormalities were detected in 48 cirrhotic patients (92 %) and in only
      nine dyspeptic patients (5.4 %) (P < 0.001). The size of extraluminal adventitial
      venous dilatation was significantly correlated with the severity of GEV and
      cirrhosis (P < 0.001). Perforating veins were identified in all patients with
      GEV. CONCLUSION: The new generation video-echo endoscope could be used as a
      single investigation in assessing both the intraluminal GEV and extraluminal
      venous abnormalities in cirrhotic patients. It may improve the management of
      patients with portal hypertension.

PMID- 11972272
TI  - Endoscopic treatment of benign anastomotic esophageal stenosis with
      electrocautery.
AB  - BACKGROUND AND STUDY AIMS: Stricture of the esophagus following surgical
      resection is uncommon. Several methods have been described for treatment of this
      entity, but the therapeutic success may be impaired either by poor long-term
      results or by poor acceptance by patients. Even the high cost of the therapeutic
      management may represent a problem. We describe the use of electrocautery to
      treat benign anastomotic esophageal stenosis. PATIENTS AND METHODS: Six
      unselected consecutive patients (four men, two women; mean age 68.3, range 54 -
      82) with stenosis following esophagojejunostomy were enrolled in this trial.
      Postoperative stenoses were shown endoscopically (four patients) or
      radiographically (two patients). We performed endoscopic dilation of the
      strictures using electrocautery. RESULTS: In all patients we obtained dilation of
      the strictures, without any immediate or delayed procedure-related complication.
      No recurrence of the stenosis was demonstrated during a mean 24-month follow-up
      (range 8 - 33 months). CONCLUSIONS: This study showed that endoscopic
      electrocautery is a safe and effective treatment for benign anastomotic
      esophageal stenosis.

PMID- 11972274
TI  - Argon plasma coagulation for treatment of watermelon stomach.
AB  - BACKGROUND AND STUDY AIMS: Watermelon stomach or gastric antral vascular ectasia
      (GAVE) is a rare but well-recognized cause of gastrointestinal blood loss, which
      typically affects elderly women. Historically patients were treated with
      antrectomy but this has been largely replaced by endoscopic therapy such as
      Nd:YAG laser. Argon plasma coagulation (APC) is a new noncontact
      electocoagulation technique which has several theoretical advantages over laser.
      The objective of this study was to assess the efficacy of APC in treating GAVE.
      PATIENTS AND METHODS: We retrospectively reviewed the case-records of five
      patients (four women, one man) with iron deficiency anaemia or gastrointestinal
      blood loss due to GAVE who were treated with APC and for whom a follow-up of more
      than 12 months was available. Four patients were transfusion-dependent. Their
      mean age was 71 years (range 58 - 83). The mode of presentation, number of
      treatment sessions, response to therapy and recurrence (if any) were recorded.
      RESULTS: A mean of 2.6 treatment sessions per patient were required. All patients
      had an endoscopically observed response to therapy and all patients had a
      sustained rise in hemoglobin level after treatment. Transfusion dependence ceased
      in all patients. After a mean follow-up of 20 months GAVE recurred in two
      patients (40 %). Both patients responded to further APC treatment. No major
      complications were recorded. CONCLUSION: APC is a safe and effective short-term
      treatment for GAVE. The natural history of the condition is uncertain, and at
      medium-term follow-up GAVE is found to recur in a substantial number of patients
      treated with APC. Re-treatment with APC is an option in these patients.

PMID- 11972273
TI  - Technical modifications and strategies for stenting gastric outlet strictures
      using esophageal endoprostheses.
AB  - BACKGROUND AND STUDY AIMS: The outcome of stenting gastric outlet stricture is
      favorable compared with a bypass operation which has significant morbidity and
      mortality. In Japan, this procedure is particularly complicated by a lack of
      enteral stents. We report some technical stratagems for stent placement for
      gastric outlet strictures. PATIENTS AND METHODS: Between February 1993 and July
      2001, 23 patients with gastric outlet strictures (14 men, nine women; mean age 72
      years) underwent stent placement using an esophageal stent system. The Ultraflex
      or Z-stents were used in 18 or five patients, respectively. With the Ultraflex,
      we increased the length of the delivery system. Some patients underwent stent
      placement with the help of endoscopic assistance with a grasping forceps or a
      home-made sheath. RESULTS: The metal stent was successfully inserted in all
      patients. There were no complications during the procedure. Migration occurred in
      two out of five patients treated with the Z-stent, whereas there was no migration
      in patients treated with the Ultraflex stent. In two patients, curable
      pancreatitis was caused by pressure on the duodenal papilla. One of these
      patients also experienced bile stasis which required biliary decompression. There
      were three cases of obstruction, caused by tumor ingrowth (1), hyperplasia (1)
      and stent fracture (1); recanalization by an additional stent placement and/or
      cutting stent filaments was successful. All the patients died, with a median
      survival period of 52 days. There was no procedure-related mortality.
      CONCLUSIONS: With some technical modification, stent placement for gastric outlet
      stricture, even using an esophageal stent, is feasible. This procedure offers
      good palliation with no major complications.

PMID- 11972275
TI  - Optimization of the diameter of a radial irradiation device for photodynamic
      therapy in the esophagus.
AB  - BACKGROUND AND STUDY AIMS: Photodynamic therapy (PDT) is a local therapeutic
      technique based on the photosensitization of lesions using a dye prior to light
      induced tissue destruction. PDT of intraepithelial neoplasia in Barrett's
      esophagus, or of early squamous-cell carcinoma of the esophagus, requires light
      application devices that allow homogeneous and well-defined illumination of the
      tissue surface. Such devices must be large enough to induce complete unfolding of
      the esophagus in spite of esophageal motility and elasticity. The aim of this
      study was therefore to determine the optimal diameter of a cylindrical
      illumination device for PDT in this organ. PATIENTS AND METHODS: The study
      included nine patients (aged 49-72 years) who underwent panendoscopy. Flexible
      transparent hollow tubes with diameters ranging from 13 to 19 mm were
      successively introduced into the esophagus, and the esophageal wall was viewed
      from the inside through the tube using a flexible small-diameter endoscope. The
      number of folds was counted. Observations of the upper, middle, and lower thirds
      of the esophagus were recorded. The radial location of the folds was also
      recorded, and defined as follows: anterior wall (up), posterior wall (down), side
      walls (right, left). RESULTS: No significant difference in the number of folds
      between the lower and middle parts of the esophagus was noticed. However, the
      upper third had significantly fewer folds (about 30 %) than the other two parts.
      For diameters above 17 mm, this difference was less dramatic. The number of such
      folds was shown to decrease with the increasing diameter of the device.
      CONCLUSIONS: It appears that 18 mm or more is the optimal diameter for a fixed
      geometry cylindrical photodynamic therapy irradiating device for the patient
      category considered in this study. It was also observed that most folds were
      located on the side walls of the esophagus.

PMID- 11972276
TI  - Enteroscopy: endangered by the capsule?

PMID- 11972277
TI  - Esophageal intramural metastasis from adenocarcinoma of the gastroesophageal
      junction.
AB  - Among a total of 143 patients examined for diagnosis of adenocarcinoma of the
      cardia, intramural esophageal metastases were verified in six patients (4.19 %).
      In each case the diagnosis was confirmed by histological examination. The
      histological structure of the primary tumors and metastases was the same.
      Metastases were detected by endoscopic ultrasound examination in three cases. All
      the cardia tumors proved to be well advanced. As well as endoscopic
      identification of the primary tumor, thorough examination of the proximal part of
      the esophagus is of great importance.

PMID- 11972278
TI  - Development of an aggressive depressed cancer in a case of familial adenomatous
      polyposis.
AB  - In 1977, Kariya et al. reported a case of a small depressed cancer in a patient
      with familial adenomatous polyposis (FAP) raising the possibility that not all
      cancers in FAP develop from polypoid adenomas. It is now becoming widely
      recognized that colonic adenomas may appear as flat or depressed lesions.
      However, colorectal cancers developing in patients with familial adenomatous
      polyposis (FAP) are still thought to evolve from adenomatous polyps following the
      polyp-carcinoma sequence. We report the case of a patient with FAP in whom rectal
      carcinoma developed 23 years after subtotal colectomy and ileorectal anastomosis.
      We suggest that this malignancy may have developed de novo because of the
      depressed shape of the lesion and the aggressive growth pattern. This case raises
      the possibility that carcinomas may not always evolve from polyps in FAP.
      Aggressive cancers with a depressed appearance should be searched for when
      surveying the rectal stump in patients with FAP.

PMID- 11972279
TI  - Awaiting the ideal metal biliary stent.

PMID- 11972281
TI  - Endoscopic resection of a large esophageal leiomyoma.

PMID- 11972282
TI  - Diminutive but dangerous: a case of a polypoid rectal arteriovenous malformation.

PMID- 11972283
TI  - Endoscopic management of colocutaneous fistula after percutaneous endoscopic
      gastrostomy.

PMID- 11972284
TI  - Wallstent and unusual gastrointestinal bleeding.

PMID- 11972285
TI  - Cyst-gastrostomy via the cyst: an unusual laparoscopic approach.

PMID- 11972286
TI  - alpha-Tocopherol Inhibits IL-8 synthesis induced by thrombin and high glucose in
      endothelial cells.
AB  - It has been reported that alpha-tocopherol, an antioxidant agent, may play a role
      in preventing diabetic angiopathy. However, there is little evidence to show the
      effect of alpha-tocopherol on the production of pro-inflammatory cytokines in
      endothelial cells. Therefore, we examined the effect of alpha-tocopherol on the
      regulation of IL-8 synthesis induced by high glucose and/or thrombin in
      endothelial cells. Thrombin alone markedly increased the IL-8 release.
      Furthermore, high glucose levels and thrombin combined had additive effects on IL
      8 synthesis, and alpha-tocopherol diminished their effect; alpha-tocopherol also
      inhibited the phosphorylation of IkappaB-alpha induced by high glucose levels
      and/or thrombin. Our results suggest that the administration of alpha-tocopherol
      to diabetic patients may have a beneficial effect for the prevention of diabetic
      vascular complications by the inhibition of IL-8 synthesis from endothelial
      cells.

PMID- 11972287
TI  - Central 5-HT3 receptor stimulation by m-CPBG increases blood glucose in rats.
AB  - The aim of the present study was to investigate the role of central 5-HT3
      receptors on the control of blood glucose in stressed and non-stressed rats in
      both fasted and fed states. Adult Wistar male rats had each their third ventricle
      cannulated 7 days before the experiments. Injections of m-CPBG, a selective 5-HT3
      receptor agonist, induced a significant increase in blood glucose in non-stressed
      rats in both fasted and in fed states. The same procedure was unable to modify
      stress-induced hyperglycemia. The hyperglycemic effect of m-CPBG central
      administration was blocked by pretreatment with ondansetron, a specific 5-HT3
      receptor antagonist, indicating that the effects here obtained with m-CPBG were a
      result of its interaction with 5-HT3 receptors. Third ventricle injections of
      ondansetron alone were not able to modify blood glucose in non-stressed animals
      and did not change the hyperglycemic responses observed after immobilization
      stress. We conclude that pharmacological activation of the central 5-HT3 receptor
      induces a hyperglycemic effect in non-stressed animals.

PMID- 11972288
TI  - Formation of compound 305 requires the simultaneous generation of both alloxan
      and GSH radicals.
AB  - This in vitro study investigates the conditions under which "compound 305" is
      formed. Using HPLC, ESR as well as UV spectroscopy, "compound 305" was largely
      separated and characterized. It has an absorption peak at 314 nm, which changes
      after reoxygenation to shorter wavelengths within hours. The retention time of
      "compound 305" amounts to 10.93 +/- 0.042 min. The formation of "compound 305"
      does not depend on alloxan (ALX) or reduced glutathione (GSH), but most likely on
      the steady-state concentration of the paramagnetic derivatives of both reactants
      (ALX* and GS*). The alloxan radical (ALX*) is formed by either a one-electron
      transfer from e. g. GSH to alloxan or oxidation of dialuric acid. The
      concentration of the ALX* was determined to be 12 +/- 3.6 micromol/l using the
      stable ultramarine radical as an ESR standard. ALX* is stable only under
      anaerobic conditions. It disappears within 2 min in air. Since formation of
      "compound 305" needs both ALX* as well as GS*, which are also necessary for the
      generation of reactive oxygen species (ROS), it is assumed that formation of
      "compound 305" diminishes the toxicity of alloxan.

PMID- 11972289
TI  - Pituitary-thyroid axis, thyroid volume and leptin in healthy adults.
AB  - OBJECTIVE: Patients with thyroid diseases usually have disturbances relating to
      body weight and thermogenesis. On the other hand, leptin is involved in the
      regulation of body weight, food intake and thermogenesis. Some studies have
      investigated the relationship between leptin and dysthyroid states, but the
      complex interactions between leptin and pituitary-thyroid axis have led to
      controversial results. DESIGN: The aims of this cross-sectional study were to
      investigate the relationship among basal TSH, ultrasonographic thyroid volume and
      leptin in a group of 268 healthy adults randomly selected from our city,
      L'Hospitalet de Llobregat, Barcelona, an area free of iodine deficiency. In this
      euthyroid group, we determined basal TSH, thyroid autoantibodies, leptin
      concentrations, and thyroid volume by ultrasonography, body anthropometry, and
      body composition. RESULTS: All subjects were free of goitre and were negative for
      anti-thyroid antibodies. Basal TSH concentrations were 1.49 +/- 0.8 mU/l in males
      and 1.67 +/- 0.83 mU/l in females (p = 0.6). Anti-thyroid antibodies were
      negative in all cases; leptin concentrations were 6.1 +/- 4 ng/ml in males and
      16.8 +/- 11.7 ng/ml in females (p = 0.0001). Thyroid volume was 9.8 +/- 4.6 ml in
      males and 6.5 +/- 2 ml in females (p = 0.001). There were significant
      correlations among leptin concentrations and anthropometric and body composition
      variables in both sexes, without correlation with TSH concentrations. There was
      no significant correlation between anthropometric and body composition variables
      and thyroid volume in males but there was a correlation in females. In females,
      there was a positive correlation between leptin and thyroid volume (r = 0.181, p
      = 0.038). In males, there was a negative correlation between TSH concentrations
      and thyroid volume (r = - 0.271, p = 0.002). CONCLUSIONS: We did not find any
      correlation between leptin levels and pituitary-thyroid axis in this control
      population. The correlation between leptin and thyroid volume in females is
      probably a consequence that leptin and thyroid volume are regulated in parallel
      by variables relating to anthropometry and body composition.

PMID- 11972290
TI  - Size at birth, fat-free mass and resting metabolic rate in adult life.
AB  - Resting metabolic rate is an important predictor of obesity and is closely
      related to fat-free mass. There is evidence that fat-free mass may be partly
      determined during critical periods of growth before and after birth. The
      objective of this study was to examine the relationship between size at birth,
      childhood growth and fat-free mass and resting metabolic rate in adult life. 318
      men and women with detailed records of body size at birth and growth during
      school years participated in the study. Fat-free mass correlated positively with
      birth weight among both sexes (r = 0.264, p < 0.001). Those having a higher birth
      weight had a higher fat-free mass at any adult BMI. Fat-free mass among men
      increased by 2.2 kg (95 % Cl 0.5 to 3.9; p = 0.01) for every kg increase in birth
      weight and by 1.5 kg (95 % Cl 1.3 to 1.7, p < 0.0001) for every kg/m(2) BMI in
      adult life. In women, fat-free mass increased by 2.7 kg (95 % Cl 1.6 - 3.9; p <
      0.001) for every kg increase in birth weight and by 0.8 kg (95 % CI 0.7 to 1.0, p
      < 0.001) for every kg/m(2) of BMI in adult life. Height, weight and body mass
      index at each age from 7 to 15 years were also strongly, positively associated
      with fat-free mass. A negative correlation between birth weight and resting
      metabolic rate expressed per unit of fat-free mass (r = - 0.158; p < 0.001) was
      found. Fat-free mass may be determined during critical periods of muscle growth
      in utero and during childhood. The muscle tissue of people who had a lower birth
      weight is more metabolically active than those with a higher birth weight. This
      may protect them from the increased risk of obesity associated with low fat-free
      mass.

PMID- 11972291
TI  - GLP-1 as a satiety factor in children with eating disorders.
AB  - GLP-1, with its insulinotropic properties and direct action on satiety center in
      the brain, may be the main hormone regulating the amount of ingested food. In
      this study, GLP-1 secretion was investigated in age-matched adolescent girls (14
      +/- 2 years): 13 with anorexia nervosa (BMI 14.8 +/- 1.4 kg/m(2)), 13 with simple
      obesity (BMI 33.0 +/- 3.3 kg/m(2)) and 10 healthy girls as a control group (BMI
      21.6 +/- 0.7 kg/m(2)). Each girl was subjected to OGTT and standard meal tests
      after a 12 h overnight fast. Blood samples were collected before and 15, 30, 60,
      and 120 min after the stimulation. The mean fasted GLP-1 levels in simple obesity
      group (1.6 +/- 0.3 pmol/l) and in anorexia nervosa group (1.7 +/- 0.3 pmol/l)
      were significantly lower than those in the control group (2.6 +/- 0.4 pmol/l) (p
      < 0.05 in both cases). The highest peak concentration of GLP-1 was observed in
      the control group after both stimuli. In each group, the mean integrated GLP-1
      outputs were almost twice as high after OGTT than after the test meal (p < 0.001
      in each case). In our opinion, low secretion of GLP-1 in girls with simple
      obesity may seriously and negatively influence the course of this disease. On the
      other hand, low GLP-1 levels in girls with anorexia nervosa are beneficial and
      promote appetite.

PMID- 11972292
TI  - Cessation of pulmonary and coronary secretion of adrenomedullin peptides in the
      progression of human heart failure.
AB  - In human heart failure (CHF), adrenomedullin (AM) counteracts vasoconstriction
      and sodium retention. We investigated circulating levels of proadrenomedullin N
      20 peptide (PAMP) and AM, and left ventricular expression of preproAM and
      calcitonin receptor-like receptor (CRLR) mRNA. Peptide levels were determined
      from the left ventricle, pulmonary artery, coronary sinus, and antecubital vein
      in patients demonstrating severe CHF (n = 12; mean +/- SEM cardiac index, 1.9 +/-
      0.2 l/min/m(2); pulmonary wedge pressure, 32 +/- 1 mmHg), moderate CHF (n = 11;
      cardiac index, 2.9 +/- 0.2; pulmonary wedge pressure, 14 +/- 2), and in controls
      (n = 11). Left ventricular mRNA was quantified using RT-PCR and Southern blot
      hybridization. Depending on sites of measurement, PAMP and AM in severe CHF were
      1.3 - 2.0 and 1.2 - 1.9 times as high as in moderate CHF, and 3.8 - 4.6 and 2.3 -
      2.8 times as high as in controls. Only patients with moderate CHF demonstrated
      pulmonary and coronary net release of both peptides, that is, significant step
      ups in concentrations between the pulmonary artery, left ventricle, and coronary
      sinus. In failing ventricles, preproAM mRNA increased 2.9 times above control,
      but CRLR mRNA was unchanged. Altogether, the heart and the lungs release AM
      peptides in moderate CHF. This secretion breaks down in severe CHF: a process
      that may contribute to and indicate decompensation. Unlike AM, the CRLR is not
      transcriptionally upregulated in severe CHF.

PMID- 11972293
TI  - Impact on lipoprotein profile after long-term testosterone replacement in
      hypogonadal men.
AB  - Testosterone serum levels may influence the lipoprotein metabolism and possibly
      atherogenic risk. Our aim was to investigate the effects of long-term
      testosterone supplementation in hypogonadal men on multiple lipoprotein markers.
      18 Hypogonadal men were studied before and after 3, 6, and 18 (n = 7) months of
      treatment with testosterone enanthate. During treatment, serum testosterone and
      estradiol increased, reaching normal levels (p < 0.0001 and 0.003, respectively).
      This was associated with a decrease in HDL cholesterol (from 1.40 +/- 0.10 mmol/l
      to 1.22 +/- 0.08 mmol/l, p < 0.001) after six months at the expense of HDL2
      cholesterol (p < 0.01), as well as apoprotein A1 (from 139 +/- 3.4 mg/dl to 126
      +/- 3.0 mg/dl, p < 0.005). Hepatic lipase activity increased (p < 0.05) and
      correlated positively with testosterone (r = 0.56, p < 0.02) and negatively with
      HDL cholesterol (r = - 0.58, p < 0.02). Total and LDL cholesterol, triglycerides,
      and apoprotein B did not increase. Among the seven patients who completed 18
      months of treatment, triglycerides, total cholesterol, LDL and HDL cholesterol,
      as well as total cholesterol/HDL cholesterol ratio values did not differ from
      baseline while apoprotein A1 (p < 0.03) and HDL cholesterol (p < 0.015) remained
      decreased and hepatic lipase unchanged. Restoration of testosterone levels in
      hypogonadal men in this study did not reveal unfavorable changes based on total
      cholesterol/HDL cholesterol and LDL cholesterol/apoprotein B ratios, which are
      both atherogenic risk markers. Whether the changes in light of lipoprotein
      metabolism will adversely influence cardiovascular risk over time remains to be
      determined.

PMID- 11972294
TI  - Substrate turnover and oxidation during moderate-intensity exercise following
      acute plasma volume expansion.
AB  - In previous work using prolonged, light cycle exercise, we were unable to
      demonstrate an effect of acute plasma volume (PV) expansion on glucose kinetics
      or substrate oxidation, despite a decline in whole-body lipolysis (Phillips et
      al., 1997). However, PV is known to decrease arterial O2 content. The purpose of
      this study was to examine whether substrate turnover and oxidation would be
      altered with heavier exercise where the challenge to O2 delivery is increased.
      Eight untrained males (VO2max = 3.52 +/- 0.12 l/min) twice performed 90 min of
      cycle ergometry at 62 % VO2peak, both prior to (CON) and following induced plasma
      volume expansion (Dextran [6 %] or Pentaspan [10 %]) (6.7 ml/kg) (PVX). Glucose
      and glycerol kinetics were determined with primed constant infusions of [6.6
      (2)H2] glucose and [(2)H5] glycerol, respectively. PVX resulted in a 15.8 +/- 2.2
      % increase (p < 0.05) in PV. Glucose and glycerol appearance (Ra) and utilization
      (Rd), although increasing progressively (p < 0.05) with exercise, were not
      different between conditions. Similarly, no differences in substrate oxidation,
      either fat or carbohydrate, were observed between the two conditions. Prolonged
      exercise resulted in an increase (p < 0.05) in plasma glucagon and a decrease (p
      < 0.05) in plasma insulin during both conditions. With PVX, the exercise-induced
      increase in glucagon was diminished (p < 0.05). We conclude that impairment in O2
      content mediated by an elevated PV does not alter glucose, and glycerol kinetics
      or substrate oxidation even at moderate exercise intensity.

PMID- 11972295
TI  - Simplified measurement of insulin sensitivity with the minimal model procedure in
      type 2 diabetic patients without measurement of insulinemia.
AB  - This study aimed to evaluate a simplified minimal model protocol for measuring
      insulin sensitivity in mild and severe type 2 diabetes, considering that changes
      in serum insulin during an insulin-modified intravenous glucose tolerance test
      almost only reflect the insulin injection. Two groups of diabetics treated with
      high doses of antidiabetic agents were recruited. Mean insulin responses were
      calculated in group 1 (n = 30). In group 2 (n = 38), we compared insulin
      sensitivity (SI) obtained with reference protocol with SI calculated by a minimal
      model procedure including the theoretical average insulin profile determined in
      group 1, and with Homeostasis Model Assessment (HOMA-R). Additionally, the cost
      of each procedure was calculated. SI measured by the reference method strongly
      correlated with SI determined by the simplified protocol (r = 0.966, p < 0.0001),
      while no correlation was found with HOMA-R (r = - 0.349, NS). Reduction of cost
      for HOMA-R and simplified minimal model procedure were - 92 and - 81 %,
      respectively. This simplified and relative inexpensive protocol, using minimal
      model procedure without insulin measurement, accurately measures SI regardless of
      beta-cell defect degree. This approach could be of interest when limits of
      validity of simple indexes are reached.

PMID- 11972296
TI  - Does gliclazide stimulate first-phase, second-phase, or both phases of insulin
      release?

PMID- 11972298
TI  - Acute stimulation of glucose uptake by leptin in l6 muscle cells.
AB  - The adipocyte hormone, leptin, acts via the central nervous system to modulate
      glucose metabolism by skeletal muscle, but the direct effects of leptin on
      glucose metabolism by skeletal muscle are unclear. In this study, we have
      examined effects of leptin on glucose uptake by cultured L6 muscle cells assessed
      with the non-metabolised glucose analogue 2-deoxy-D-glucose. Reverse
      transcriptase polymerase chain reaction (RT-PCR) analysis of RNA showed that L6
      muscle cells express a short isoform of the leptin receptor (ObRa), but not the
      long isoform (ObRb). In the absence of added insulin, incubation of L6 muscle
      cells with murine leptin (10( -11)-10( -8) M) for 10 min and 1 h increased
      glucose uptake by 15 % - 23 %. This effect of leptin was lost by 4 h. Leptin (10(
      -10) - 10( -9) M) initially (after 10 min) suppressed insulin-stimulated glucose
      uptake by 14 - 16 %, but had no effect in the longer term. Leptin-stimulated
      glucose uptake was inhibited by the phosphatidylinositol 3-kinase (PI3K)
      inhibitor wortmannin, but not by the janus kinase-2 (JAK-2) inhibitor tyrphostin
      AG490. The results suggest that leptin can act directly on L6 muscle cellsvia a
      short leptin receptor isoform to acutely stimulate basal (but not insulin
      stimulated) glucose uptake via a PI3K-dependent pathway.

PMID- 11972299
TI  - Evidence for the biosynthesis of DHEA from cholesterol by first-trimester human
      placental tissue: source of androgens.
AB  - With a view to establishing whether first-trimester human placentas possess the
      ability to synthesize DHEA from cholesterol, homogenates of this tissue obtained
      from two groups of women undergoing elective termination of normally progressing
      pregnancy between 10 - 12 weeks gestation (n = 5, age 23 - 29 years and n = 5,
      age 21 - 27 years) were incubated separately with [26-(14)C]cholesterol for the
      generation of [14C]isocaproic acid + pregnenolone and [7n-3H]pregnenolone for the
      biosynthesis of [3H]DHEA. Controls consisted of homogenates heated in a boiling
      water bath for 10 min. Using the reverse-isotope dilution analysis, desmolase
      efficiency expressed as mean specific activity of [14C]isocaproic acid varied
      from 282 to 725 dpm/mmol, while that of 17 alpha-hydroxylase and steroid C-17,20
      lyase, catalyzed conversion of [7n-3H]pregnenolone to [3H]DHEA varied from 3498
      to 26 258 dpm/mmol. The corresponding efficiencies of enzymicconversion varied
      between 5.8 x 10( -2) and 1.5 x 10( -1) % for [14C]isocaproic acid, but between
      5.5 x 10( -2) and 4.1 x 10( -1) % for [3H]DHEA. No such metabolite was evident in
      the controls of heat-denatured homogenates. These are the first study results to
      demonstrate that early placentas are capable of converting cholesterol to
      pregnenolone to DHEA, contrary to the widely held concept of DHEA production by
      fetal and maternal adrenal glands. This finding has important physiological
      implications and could provide a new dimension to the concept of fetoplacental
      steroidogenesis.

PMID- 11972300
TI  - Effects of 5-campestenone (24-methylcholest-5-en-3-one) on the type 2 diabetes
      mellitus model animal C57BL/KsJ-db/db mice.
AB  - We examined the therapeutic effects of dietary exposure to 5-campestenone (24
      methylcholest-5-en-3-one), an enone derivative of campesterol, in C57BL/KsJ-db/db
      mice, which are an animal model of obese type 2 diabetes. Blood glucose levels of
      db/db mice linearly increased from 270 to 720 mg/dl in 10 weeks, an approximately
      7-fold difference from the levels of db/+m mice. The 0.3 % dietary exposure to 5
      campestenone caused a marked reduction in blood glucose levels of 330 mg/dl after
      10 weeks of feeding with a concomitant inhibition of glucose excretion in urine.
      Only slight efficacy was observed with 0.1 % dietary exposure to this chemical in
      db/db mice. Significant decreases of plasma triglyceride and plasma free fatty
      acid were also observed in db/db mice at a 0.3 % dose. However, feed efficiency
      and body-weight gain in db/db mice was improved by 5-campestenone. No obvious
      anomaly due to consumption of 5-campestenone was detected by necropsy or clinical
      observation.

PMID- 11972301
TI  - Dehydroepiandrosterone status in postmenopausal women is determined by the gene
      for the vitamin D receptor.
AB  - Data documenting the indirect interaction of vitamin D and bone metabolism via
      hormonal systems are rare. The authors analysed the predictive role of the
      vitamin D receptor (VDR) gene for circulating sex steroids and their precursors
      in postmenopausal women. Using the PCR technique, the polymorphic FokI, ApaI,
      TaqI and BsmI sites of the VDR gene were determined in relation to serum
      dehydroepiandrosterone sulphate (DHEAS), androstenedione (AD), testosterone, and
      estradiol levels. After adjustment to body mass and years since menopause,
      circulating DHEAS was higher in the Ff genotype than in ff (p < 0.001) and FF
      genotypes (p < 0.05, ANCOVA followed by least significant difference multiple
      comparison tests). The Ff genotype also contributed to the highest BMD at the hip
      (p < 0.01 as compared to ff genotype) and at the spine (p < 0.05). No significant
      associations were found between ApaI, TaqI and BsmI polymorphisms and serum DHEAS
      or between FokI, ApaI, TaqI or BsmI and serum androstenedione, testosterone or
      estradiol. The study shows that the VDR gene predicts synthesis and/or metabolism
      of sexual steroid preursor DHEA in parallel with bone mineral density (BMD). The
      results indicate that DHEA production and bone mass share a common genetic
      control through VDR.

PMID- 11972302
TI  - Evidence for greater oxidative substrate flexibility in male carriers of the Pro
      12 Ala polymorphism in PPARgamma2.
AB  - The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor
      gamma2 (PPARgamma2) gene is associated with reduced type 2 diabetes risk and
      increased insulin sensitivity. It is possible that the oxidative shift from lipid
      to glucose as a fuel is more efficient in Ala allele carriers. To test this
      hypothesis, we examined carbohydrate and lipid oxidation by indirect calorimetry
      in lean, glucose tolerant subjects with (X/Ala, n = 25) and without the Pro12Ala
      polymorphism (Pro/Pro, n = 73) basally and after insulin stimulation during a 2
      hour eugylcaemic hyperinsulinaemic clamp. Insulin sensitivity was non
      significantly greater in X/Ala (0.13 +/- 0.01 micromol/kg/min/pM) than in Pro/Pro
      (0.12 +/- 0.01 micromol/kg/min/pM, p = 0.27). Basally, there were no lipid nor
      carbohydrate oxidation differences between the groups. Interestingly, the
      decrease in lipid oxidation during insulin stimulation was significantly greater
      in male X/Ala (- 0.51 +/- 0.06 mg/kg/min) than in male Pro/Pro (- 0.35 +/- 0.04
      mg/kg/min, p = 0.03). No difference was observed in females. Analogously, the
      change in carbohydrate oxidation in male X/Ala (1.34 +/- 0.2 mg/kg/min) was
      significantly greater than in male Pro/Pro (1.03 +/- 0.12 mg/kg/min, p = 0.05).
      The respiratory quotient increased more, but not significantly more, in male
      X/Ala (0.11 +/- 0.01) than in male Pro/Pro subjects (0.08 +/- 0.01, p = 0.08) but
      similarly in females. These results indicate that the mechanism by which the Ala
      allele improves insulin sensitivity might involve enhanced suppression of lipid
      oxidation permitting more efficient (predominantly non-oxidative) glucose
      disposal. It is unclear why this could be demonstrated only in males, although
      gender differences in substrate oxidation are well documented.

PMID- 11972303
TI  - A retrospective hormonal and immunohistochemical evaluation of 47 acromegalic
      patients: prognostic value of preoperative plasma prolactin.
AB  - This study was performed to investigate the correlations between preoperative
      prolactin (PRL) plasma values, immunohistochemical picture and the clinical
      course in growth hormone (GH) secreting pituitary adenomas. In 47 patients (19
      males and 28 females; mean age 40 years; range 13 - 70 years), we measured GH,
      IGF-1 and prolactin plasma values both before and after transsphenoidal surgery,
      and basal IGF-1 and GH after an oral glucose tolerance test (OGTT) during four
      years of follow-up. We considered those patients as "controlled" who presented an
      undetectable growth hormone after OGTT (GH < 1 microg/l), IGF-I plasma values in
      the normal range, matched for age and sex, and no clinical activity or
      neuroradiological recurrence after a four-year follow-up. We considered patients
      as "poorly controlled" who still showed elevated GH and IGF-I plasma levels,
      uninhibited GH after OGTT (GH > 1 microg/l), presence of clinical activity and/or
      radiological signs of adenoma recurrence, even if a reduction of tumor size had
      been demonstrated. RESULTS: Controlled patients (n = 22) exhibited mean
      preoperative PRL levels (+/- SEM) lower than the group of poorly controlled (n =
      25) ones (21.40 +/- 5.51 vs. 38.44 +/- 5.16 microg/l; p < 0.03). From 3 to 12
      months after surgery, postoperative PRL levels were also lower in the controlled
      patients compared to the poorly controlled ones (8.31 +/- 1.20 vs. 25.32 +/- 3.20
      microg/l; p < 0.0001). Eighty percent (20/25) of poorly controlled patients
      showed both PRL and GH positivity after immunostaining. Only 3/22 (13.6 %) of
      controlled patients showed the same double positivity. In conclusion,
      preoperative hyperprolactinemia identifies a group of acromegalic patients at
      elevated risk of disease persistence after surgery. We hypothesize that most of
      these high-risk patients may have more aggressive mixed GH-PRL secreting
      adenomas.

PMID- 11972304
TI  - High serum insulin-like growth factor binding protein-1 is associated with
      increased cardiovascular mortality in elderly men.
AB  - Insulin-like growth factor binding protein-1 (IGFBP-1) has been implicated in the
      development of cardiovascular disease, but it is not known whether IGFBP-1 is
      related to cardiovascular mortality. We examined the relation of circulating
      IGFBP-1 to death from coronary heart disease, cardiovascular disease, and all
      causes in a cohort study consisting of 622 men aged 65 - 84 years, at baseline in
      1984. Fasting serum IGFBP-1 and other risk factors were measured in 1984 and
      1989. Cardiovascular events for those who died between 1984 and 1995 were
      analyzed, and cardiovascular diagnoses were coded centrally according to
      standardized procedures. Of the 622 men, 358 died between 1984 and 1995; 160
      deaths were due to cardiovascular causes, 113 of which were coronary deaths. High
      fasting serum IGFBP-1 concentration (> 75 percentile) in 1984 was associated with
      increased five-year total mortality (OR 2.05, 95 % CI 1.41 - 2.99; p < 0.0002),
      cardiovascular mortality (OR 2.20, 95 % CI 1.37 - 3.50; p < 0.0009) and coronary
      heart disease mortality (OR 2.29, 95 % CI 1.35 - 3.88; p < 0.002). After
      adjustment for age, high serum IGFBP-1 concentrations still carried an increased
      risk of total mortality due to (OR 1.73, 95 % CI 1.16 - 2.59; p < 0.007),
      cardiovascular (OR 1.91 95 % CI 1.18 - 3.09; p < 0.008) and coronary heart
      disease (OR 2.02. 95 % CI 1.18 - 3.47; p < 0.01). In conclusion, high fasting
      serum IGFBP-1 is related to increased five-year total and cardiovascular
      mortality in elderly men.

PMID- 11972305
TI  - Evidence for early impairment of glucagon-like peptide 1-induced insulin
      secretion in human type 2 (non insulin-dependent) diabetes.
AB  - To investigate a possible role of an enteroinsular axis involvement in the
      pathogenesis of type 2 diabetes, plasma glucagon-like peptide 1 (GLP-1) 7-36
      amide response to nutrient ingestion was evaluated in type 2 diabetics affected
      by different degrees of beta-cell dysfunction. METHODS: 14 patients on oral
      hypoglycaemic treatment (group A: HbA1C = 8.1 +/- 1.8 %) and 11 age-matched
      diabetic patients on diet only (group B: HbA1C = 6.4 +/- 0.9) participated in the
      study. 10 healthy volunteers were studied as controls. In the postabsorptive
      state, a mixed meal (700 kCal) was administered to all subjects, and blood
      samples were regularly collected up to 180' for plasma glucose, insulin,
      glucagon, and GLP-1 determination. RESULTS: In the control group, the test meal
      induced a significant increase in plasma GLP-1 at 30' and 60' (p < 0.01); the
      peptide concentrations then returning toward basal levels. beta-cell function
      estimation by HOMA score confirmed a more advanced involvement in group A than in
      group B (p < 0.01). In contrast, the insulin resistance degree showed a similar
      result in the two groups (HOMA-R). In group A, first-phase postprandial insulin
      secretion (0 - 60') resulted, as expected, in being significantly reduced
      compared to healthy subjects (p < 0.001). In the same patients the mean fasting
      GLP-1 value was similar to controls, but the meal failed to increase plasma
      peptide levels, which even tended to decrease during the test (p < 0.01). In
      group B, food-mediated early insulin secretion was higher than in group A (p <
      0.001), although significantly reduced when compared to controls (p < 0.01). Like
      group A, no GLP-1 response to food ingestion occurred in group B patients in
      spite of maintained basal peptide secretion. Whereas the test-meal did not
      significantly modify plasma glucagon levels in the control group, glucagon
      concentrations increased at 30' and 60' in both diabetic groups (p < 0.01).
      CONCLUSIONS: 1) The functional integrity of GLP-1 cells results as being
      seriously impaired even in the condition of mild diabetes; 2) the early peptide
      failure could contribute to the development of beta-cell deterioration which
      characterizes overt type 2 diabetes.

PMID- 11972307
TI  - Elevation of serum thioredoxin levels in patients with type 2 diabetes.
AB  - To evaluate the clinical significance of thioredoxin in diabetic patients, serum
      thioredoxin levels measured with a recently established sandwich enzyme-linked
      immunosorbent assay kit were compared with clinical laboratory data and
      complications in 174 patients with Type 2 diabetes. Thioredoxin levels were
      significantly higher in diabetic patients (mean value, 38 ng/ml) than in healthy
      controls (21 ng/ml) (p < 0.05). Fasting blood sugar and hemoglobin A1c did not
      correlate with thioredoxin. Plasma non-esterified fatty acids levels were
      significantly higher in patients with higher thioredoxin levels (>or= 40 ng/ml)
      than in those with lower thioredoxin levels (< 40 ng/ml) (p < 0.001). There was a
      significant correlation both between thioredoxin and non-esterified fatty acids
      in patients with diet/exercise therapy (p < 0.01) and between thioredoxin and
      fasting immunoreactive insulin in those treated with diet/exercise or oral
      hypoglycemic agents (p < 0.05). Thioredoxin did not correlate with diabetic
      complications. In conclusion, serum thioredoxin levels may reflect the status of
      insulin resistance in Type 2 diabetic patients.

PMID- 11972306
TI  - Effect of simulated microgravity on endocrine response to insulin-induced
      hypoglycemia in physically fit men.
AB  - Adaptation to microgravity is associated with alteration in some endocrine
      functions. In the present longitudinal study, the counterregulatory hormonal
      response to insulin-induced hypoglycemia (ITT, 0.1 IU/kg short acting insulin i.
      v.) was evaluated under simulated microgravity conditions in 15 physically fit
      subjects. ITT was performed at the beginning of the investigation, and again
      after completion of 6 weeks of endurance training and after a subsequent period
      of 4 days of head-down bed rest at a backward tilt of 6 degrees from the
      horizontal. Endurance training showed a significant increase in maximal aerobic
      capacity in previously well-trained subjects (increase by 12 %), as well as on
      attenuation of counterregulatory response of epinephrine to hypoglycemia. After 4
      days of bed rest, basal concentrations of plasma norepinephrine was diminished (p
      < 0.002) and plasma renin activity was enhanced (p < 0.02). After bed rest,
      decreased responses of the two catecholamines (norepinephrine, p < 0.001;
      epinephrine, p < 0.001), growth hormone (p < 0.001), and cortisol (p < 0.05) were
      observed. Response of plasma renin activity after bed rest was increased (p <
      0.01). This longitudinal study indicated that 4 days of bed rest in endurance
      trained subjects induced increased response of PRA to hypoglycemia and
      attenuation of other counterregulatory neuroendocrine responses.

PMID- 11972308
TI  - Endothelin-1 stimulates glucose transport in murine 3T3 adipocyte lineage, but
      not in human subcutaneous fat cells.

PMID- 11972310
TI  - Megestrol acetate to correct the nutritional status in an adolescent with growth
      hormone deficiency: Increase of appetite and body weight but only by increase of
      body water and fat mass followed by profound cortisol and testosterone depletion.
AB  - Megestrol acetate (MA) is a synthetic, orally active derivative of the naturally
      occurring hormone progesterone. MA is increasingly used to correct loss of
      appetite and improve the nutritional status. We used MA in an adolescent with
      growth hormone (GH) deficiency due to former irradiation therapy in order to
      evaluate if MA can improve the nutritional status. In fact, MA increased appetite
      and weight dose-dependent. The energy expenditure measured by indirect
      calorimetry changed from hypo- to normometabolism. However, weight gain was first
      primarily due to an increase in body water and then in fat mass. The gain of fat
      mass was much more prominent than the gain of fat free mass. As important side
      effect, MA lead to rapid and profound cortisol and testosterone depletion after
      only 10 days with a long-lasting effect on testosterone depletion. Therefore, MA
      as a single therapy cannot be recommended to improve the nutritional status. If
      MA is given, cortisol and testosterone levels have to be monitored and
      supplemented as needed.

PMID- 11972309
TI  - [Prader-Labhart-Willi syndrome in infants].
AB  - We report an infant with severe hypotonia, feeding problems and failure to thrive
      in the neonatal period, followed by developmental delay. In addition, pale skin,
      eyelid and pedal edema, cryptorchidism and micrognathia were present. The
      tentative diagnosis of Prader-Labhart-Willi syndrome was made and confirmed by
      specific molecular testing at the age of 5 months. The Prader-Labhart-Willi
      syndrome is usually diagnosed in older infants when the main clinical features
      such as obesity, short stature, hypogonadism and developmental delay become
      obvious, in most of the patients typical clinical features are present already in
      the neonatal period. In conclusion, in neonates and young infants presenting with
      hypotonia and feeding problems, the Prader-Labhart-Willi syndrome should be
      considered.

PMID- 11972311
TI  - [The importance of conventional radiographs in the diagnosis of osteosarcoma].
AB  - We report about a 12-year-old boy with a history of recurrent patella luxation.
      Due to persistent pain in the distal left femur a MRI examination was performed
      in another hospital which suggested a malignant bone tumor. Without validation of
      the MRI findings by conventional radiographs bone biopsy was performed.
      Histopathological examination yielded the diagnosis of a chondroblastic
      osteosarcoma. Before initiating polychemotherapy, plain radiographs for the first
      time, a nuclear imaging study and an additional MRI examination were performed in
      our hospital. The results of these studies made the diagnosis of an osteosarcoma
      unlikely. In particular, plain radiographs did not show any osseous lesion which
      was characteristic of an osteosarcoma. To establish a definite diagnosis biopsy
      was repeated with resection of the bone area which showed suspicious changes in
      MRI studies. An osteosarcoma was ruled out by histopathological examination. The
      pathologic changes detected in MRI were rated as bone bruise on plain radiographs
      and seemed to be of traumatic origin. Our case report emphasises the importance
      of conventional radiographs in establishing the diagnosis of an osteoarcoma
      respectively bone tumors and tumor-like lesions in general. They still remain the
      mainstay in diagnosing bone forming tumors. MRI imaging studies may show changes
      which mimick solid lesions but in deed can be of traumatic origin. Without
      informing the pathologist about the exact origin of the specimen,
      histopathological examination may lead to the misdiagnosis of a chondroblastic
      osteosarcoma if specimen, like in this case report, represents epiphyseal tissue
      showing cartilaginous areas with reactive bone formation.

PMID- 11972312
TI  - [Children with epilepsy - psychiatric and neuropsychological results in
      comparison to healthy children].
AB  - QUESTIONS: Do children with epilepsy exhibit psychiatric, intellectual or motoric
      symptoms compared to healthy children? How relevant is the type of epilepsy?.
      METHODS: Children with diagnosed epilepsy aged 6 - 15 years were investigated by
      means of an established neuropsychological test program. Under anticonvulsive
      therapy the children were free from epileptic seizures. Exclusion criteria were
      neurological diseases and mental retardation. A structured interview was
      performed and psychiatric symptoms were registered. Tests performed included non
      verbal intelligence, general motor skills, concentration ability, speech,
      mathematics, and find motor skills. RESULTS: Altogether 102 children with
      epilepsy (absences N=27, grand-mal N=31, Rolandi N=17, symptomatic focal N=27)
      and a control group of healthy children of the same size were investigated. In
      children with epilepsy no psychiatric symptoms were observed. In all tests
      applied, children with epilepsy obtained poorer neuropsychological results than
      the healthy control group. Children with primarily generalised epilepsy exhibited
      markedly poorer results in data processing, speech, and fine motor skills as
      compared to the healthy group. Children with symptomatic focal epilepsy showed
      the poorest results with regard to all parameters tested. CONCLUSION: In the
      psychological test performed, children with epilepsy exhibited distinct
      differences compared to the control group, but no differences in the psychiatric
      evaluation.

PMID- 11972314
TI  - [Acute Renal Failure in Twin-to-Twin Transfusion Syndrome: Differential
      Diagnosis].
AB  - In the differential diagnosis of acute renal failure in Newborns prerenal, renal
      and postrenal causes must be considered. Additionally, in twin-to-twin
      transfusion syndrome especially the donor can suffer from acute renal failure
      caused by longterm intrauterine hypoperfusion of the kidneys resulting in severe
      retardation of renal development.

PMID- 11972313
TI  - [Splenic sequestration in patients with sickle cell disease. ].
AB  - Splenic sequestration is a potentially life threatening event that is
      characteristic for sickle cell disease. For reasons unknown a fraction of or even
      the entire blood volume is trapped in the splenic sinuses within a few hours and
      thus is no longer available for circulation. The result is splenomegaly,
      hypovolemia, anemia and extreme reticulocytosis. If the sequestered blood volume
      is very large the patient goes into fatal hypovolemic shock unless transfused
      instantly. If the sequestered volume is small there is a chance of spontaneous
      resolution. The etiology of splenic sequestration is not known. Children with
      homozygous sickle cell disease (HbSS) are at risk until age 6 years while
      individuals with compound heterozygous disease (HbSbetaThal, HbSC, HbSD) may
      develop splenic sequestration even in adulthood. Parents of infants and toddlers
      with sickle cell disease need to learn how to palpate the spleen in order to
      detect splenomegaly as early as possible and take the child to the hospital.
      Splenic sequestration with a drop in hemoglobin of more than 3 g/dl below the
      patient's usual hemoglobin level is a clear indication for splenectomy regardless
      of the patient's age as splenic sequestration tends to recur.

PMID- 11972315
TI  - [Infratentorial pathology a pitfall for neonatal cerebral sonography: Additional
      sonographic imaging through the posterolateral fontanelle, a prospective study].
AB  - BACKGROUND: Routine assessment of the neonatal brain is performed by ultrasound
      through the anterior fontanelle. The infratentorial structures can be visualised
      more detailed by sonography through the posterolateral fontanelle. This
      prospective study was performed to evaluate anterior fontanelle and
      posterolateral fontanelle for the detection of infratentorial lesions. PATIENTS:
      Cerebral sonography was performed in 100 preterm infants at the median (range)
      age of 9 days (0 - 91 days). Median gestational age at birth was 33 weeks (23 -
      36 weeks). METHOD: Scanning through the posterolateral fontanelle was performed
      after sonography through the anterior fontanelle. RESULTS: Neuropathology could
      be detected in 22 of the 100 preterms. In six patients infratentorial lesions
      were present in association with supratentorial pathology. The infratentorial
      abnormalities were clots in the IV. ventricle (n=3), clots in the cisterna magna
      (n=2), dilation of the IV. ventricle (n=3), dilation of the aqueduct (n=1), and a
      intraparenchymatous echodensity in the cerebellum (n=1) which receded. When clots
      were present in the lateral ventricles only the sonography through the
      posterolateral fontanelle allowed the detection of the infratentorial
      abnormalities. CONCLUSION: Sonography through the posterolateral fontanelle
      allows the detection of infratentorial pathology missed by sonography through the
      anterior fontanelle. Additional scanning through the posterolateral fontanelle
      should be part of the standard neonatal cerebral sonography.

PMID- 11972316
TI  - [Successful partial lysis of a 4-level-thrombosis by rt-PA - case report].
AB  - Thromboembolism of the vena cava, the venae iliaca communis, externa, femoralis,
      poplitea, and the fibular vein group of the left lower limb was diagnosed in a 13
      year old girl. Several thrombogenic risk factors (APC-resistence, homocystinuria,
      contraception, smoking) were identified. Due to painful symptoms and for
      prevention of postthrombotic syndrome continuous systemic thrombolysis with rt-PA
      (0,5 mg/kg/d), in addition to heparine, was performed for 6 days. Diagnostic
      imaging at the end of therapy demonstrated complete and partial recanalization of
      the vena cava inferior, venae iliaca communis and externa. The distal veins of
      the leg remained occluded. After catheterization of the internal jugular vein and
      placement of a cava filter only mild pulmonary embolism occurred during systemic
      thrombolysis. No further complications were observed. All in all, therapy was
      tolerated well. Systemic thrombolysis with rt-PA in children and adolescents,
      although not established for regular treatment, is an effective therapeutic
      option in severe venous thrombosis.

PMID- 11972317
TI  - [Ambulant training programs for obese children. Criterions of comparison for the
      development of valid therapy recommendations].
AB  - Valid knowledge concerning structure and contents of an ambulant training program
      for obese children and adolescents suggested by experts is still missing. In
      1999/2000, we assessed a survey based on defined criterions in the
      "Arbeitsgemeinschaft fur padiatrische Diathetik (APD)" and investigated the
      literature to cover and to compare based on defined criterions the spectrum of
      ambulant treatment models in Germany to advance guidelines for therapy in obese
      children. 13 ambulant training programs were detected. Training of children aged
      8 to 12 years and their parents based on diet, behavioural treatment and sports
      therapy over couple of months without great experiences and without complete
      financing by health insurance were in common. Time volume of the training
      programs widely varies. In the seven evaluated training programs, up to one third
      of the patients broke off, while more than two third of the children successfully
      finished the training programs. The comparison of the programs failed on missing
      data concerning the collective, missing or different evaluation criteria,
      sometimes low number of patients and not standardised calculation of overweight.
      The survey reflects the often low experiences and the heterogeneous, insufficient
      evaluation of ambulant treatment models in Germany and demonstrates the great
      requirement of research. The schedule of criterions facilitates the comparison of
      programs to develop valid ambulant training programs for obese children.

PMID- 11972318
TI  - [Transthoracic pacing in a very low birth weight infant with congenital complete
      atrioventricular block - Case report].
AB  - We report our experience of pacemaker treatment in a premature infant of 832
      grams with congenital complete atrioventricular block due to maternal Sjogren's
      Syndrome. She was delivered by cesarean section at an estimated gestational age
      of 26 weeks because of fetal bradycardia, decreasing fetal movements and hydrops.
      Immediate postnatal transesophageal ventricular pacing was not successful,
      whereas transthoracic pacing with self-adhesive patch electrodes adapted to body
      size resulted in an effective increase of the infant's heart rate until operative
      application of temporary epimyocardial pacing wires ensured the external
      stimulation of the heart.

PMID- 11972319
TI  - [Systemic lupus erythematosus-associated endocarditis in a 7-years-old girl].
AB  - Systemic Lupus erythematosus (SLE) is a chronic inflammatory disease, caused by a
      fault of the immune regulation. The etiology of the SLE is still unknown, a
      possible virus infection is discussed. Libman Sacks endokarditis is the most
      important cardiac manifestation of this illness. Diagnosis, therapy and clinical
      course of a 7 years old so far healthy girl, which suffered from an acute Libman
      Sacks-Endocarditis, are presented.

PMID- 11972320
TI  - Homology induction: the use of machine learning to improve sequence similarity
      searches.
AB  - BACKGROUND: The inference of homology between proteins is a key problem in
      molecular biology The current best approaches only identify approximately 50% of
      homologies (with a false positive rate set at 1/1000). RESULTS: We present
      Homology Induction (HI), a new approach to inferring homology. HI uses machine
      learning to bootstrap from standard sequence similarity search methods. First a
      standard method is run, then HI learns rules which are true for sequences of high
      similarity to the target (assumed homologues) and not true for general sequences,
      these rules are then used to discriminate sequences in the twilight zone. To
      learn the rules HI describes the sequences in a novel way based on a
      bioinformatic knowledge base, and the machine learning method of inductive logic
      programming. To evaluate HI we used the PDB40D benchmark which lists sequences of
      known homology but low sequence similarity. We compared the HI methodology with
      PSI-BLAST alone and found HI performed significantly better. In addition,
      Receiver Operating Characteristic (ROC) curve analysis showed that these
      improvements were robust for all reasonable error costs. The predictive homology
      rules learnt by HI by can be interpreted biologically to provide insight into
      conserved features of homologous protein families. CONCLUSIONS: HI is a new
      technique for the detection of remote protein homology--a central bioinformatic
      problem. HI with PSI-BLAST is shown to outperform PSI-BLAST for all error costs.
      It is expect that similar improvements would be obtained using HI with any
      sequence similarity method.

PMID- 11972322
TI  - Synthesis and recognition by DNA polymerases of a reactive nucleoside, 1-(2-deoxy
      beta-D-erythro-pentofuranosyl)-imidazole-4-hydrazide.
AB  - We report the synthesis of a new nucleoside, 1-(2-deoxy-beta-D-erythro
      pentofuranosyl)-imidazole-4-hydrazide (dY(NH2)) as a reactive monomer for DNA
      diversification. The 5'-triphosphate derivative (dY(NH2)TP, 1) was evaluated in
      vitro as a substrate for several DNA polymerases. Primer extension reactions
      showed that dYNH2TP was well tolerated by KF (exo(-)) and Vent (exo-) DNA
      polymerases. One dYNH2MP was incorporated opposite each canonical base with an
      efficiency depending on the template base (A approximately T > G > C).
      Significant elongation after YNH2 incorporation was observed independently of the
      YNH2:N base pair formed. When the nucleobase YNH2 was incorporated into synthetic
      oligodeoxynucleotides via the phosphoramidite derivative 11, it directed the
      insertion of natural bases as well as itself. The mutagenicity of dYNH2TP was
      evaluated by PCR amplification using Vent (exo-) DNA polymerase. The triphosphate
      dY(NH2)TP was preferentially incorporated as a dATP or dGTP analogue and led to
      misincorporations at frequencies of approximately 2 x 10(-2) per base per
      amplification. A high proportion of transversions with a large distribution of
      all possible mutations was obtained. The reactivity of the nucleobase YNH2 within
      a template with several aldehydes was demonstrated.

PMID- 11972321
TI  - Structural, functional, and evolutionary analysis of moeZ, a gene encoding an
      enzyme required for the synthesis of the Pseudomonas metabolite, pyridine-2,6
      bis(thiocarboxylic acid).
AB  - BACKGROUND: Pyridine-2,6-bis(thiocarboxylic acid) (pdtc) is a small secreted
      metabolite that has a high affinity for transition metals, increases iron uptake
      efficiency by 20% in Pseudomonas stutzeri, has the ability to reduce both soluble
      and mineral forms of iron, and has antimicrobial activity towards several species
      of bacteria. Six GenBank sequences code for proteins similar in structure to
      MoeZ, a P. stutzeri protein necessary for the synthesis of pdtc. RESULTS:
      Analysis of sequences similar to P. stutzeri MoeZ revealed that it is a member of
      a superfamily consisting of related but structurally distinct proteins that are
      members of pathways involved in the transfer of sulfur-containing moieties to
      metabolites. Members of this family of enzymes are referred to here as MoeB,
      MoeBR, MoeZ, and MoeZdR. MoeB, the molybdopterin synthase activating enzyme in
      the molybdopterin cofactor biosynthesis pathway, is the most characterized
      protein from this family. Remarkably, lengths of greater than 73% nucleic acid
      homology ranging from 35 to 486 bp exist between Pseudomonas stutzeri moeZ and
      genomic sequences found in some Mycobacterium, Mesorhizobium, Pseudomonas,
      Streptomyces, and cyanobacteria species. CONCLUSIONS: The phylogenetic
      relationship among moeZ sequences suggests that P. stutzeri may have acquired
      moeZ through lateral gene transfer from a donor more closely related to
      mycobacteria and cyanobacteria than to proteobacteria. The importance of this
      relationship lies in the fact that pdtc, the product of the P. stutzeri pathway
      that includes moeZ, has an impressive set of capabilities, some of which could
      make it a potent pathogenicity factor.

PMID- 11972324
TI  - Over-representation of repeats in stress response genes: a strategy to increase
      versatility under stressful conditions?
AB  - The survival of individual organisms facing stress is enhanced by the induction
      of a set of changes. As the intensity, duration and nature of stress is highly
      variable, the optimal response to stress may be unpredictable. To face such an
      uncertain future, it may be advantageous for a clonal population to increase its
      phenotypic heterogeneity (bet-hedging), ensuring that at least a subset of cells
      would survive the current stress. With current techniques, assessing the extent
      of this variability experimentally remains a challenge. Here, we use a
      bioinformatic approach to compare stress response genes with the rest of the
      genome for the presence of various kinds of repeated sequences, elements known to
      increase variability during the transfer of genetic information (i.e. during
      replication, but also during gene expression). We investigated the potential for
      illegitimate and homologous recombination of 296 Escherichia coli genes related
      to repair, recombination and physiological adaptations to different stresses.
      Although long repeats capable of engaging in homologous recombination are almost
      absent in stress response genes, we observed a significant high number of short
      close repeats capable of inducing phenotypic variability by slipped-mispair
      during DNA, RNA or protein synthesis.

PMID- 11972323
TI  - Charge neutralization and DNA bending by the Escherichia coli catabolite
      activator protein.
AB  - We are interested in the role of asymmetric phosphate neutralization in DNA
      bending induced by proteins. We describe an experimental estimate of the actual
      electrostatic contribution of asymmetric phosphate neutralization to the bending
      of DNA by the Escherichia coli catabolite activator protein (CAP), a prototypical
      DNA-bending protein. Following assignment of putative electrostatic interactions
      between CAP and DNA phosphates based on X-ray crystal structures, appropriate
      phosphates in the CAP half-site DNA were chemically neutralized by
      methylphosphonate substitution. DNA shape was then evaluated using a semi
      synthetic DNA electrophoretic phasing assay. Our results confirm that the
      unmodified CAP DNA half-site sequence is intrinsically curved by 26 degrees in
      the direction enhanced in the complex with protein. In the absence of protein,
      neutralization of five appropriate phosphates increases DNA curvature to 32
      degrees (approximately 23% increase), in the predicted direction. Shifting the
      placement of the neutralized phosphates changes the DNA shape, suggesting that
      sequence-directed DNA curvature can be modified by the asymmetry of phosphate
      neutralization. We suggest that asymmetric phosphate neutralization contributes
      favorably to DNA bending by CAP, but cannot account for the full DNA deformation.

PMID- 11972325
TI  - A putative RNA editing from U to C in a mouse mitochondrial transcript.
AB  - Recently, we isolated and characterized a new mouse mitochondrial RNA molecule
      containing the mitochondrial 16S RNA plus 121 nt joined to the 5' end of the RNA.
      This fragment arises from the L strand of the same gene and we have named this
      transcript chimeric RNA. At position 121 of the RNA there is a C, which,
      according to the sequence of the mitochondrial 16S RNA gene, should be a U. We
      hypothesized that this RNA is synthesized having a U at position 121, which is
      later substituted to a C by a putative editing reaction. Based on the presence of
      sites for the restriction endonucleases RsaI and Fnu4HI around position 121, both
      forms of the RNA were detected in mouse tissues. To confirm the presence of the
      non-edited and putative edited RNA, a fragment containing the first 154 nt of the
      RNA was amplified by RT-PCR and cloned. The substitution of U for C was
      demonstrated by sequencing these clones. In vitro transcription experiments
      demonstrated that the substitution of U for C is not due to artifact of
      amplification or cloning. Moreover, in mitochondria from testis only the non
      edited form was found. This, together with other experimental evidence,
      demonstrated that the base substitution was not due to polymorphism of the
      mitochondrial 16S RNA gene. This is the first demonstration of a substitution
      reaction from U to C in a mammalian mitochondrial transcript.

PMID- 11972326
TI  - Pyrococcus genome comparison evidences chromosome shuffling-driven evolution.
AB  - The genomes of three Pyrococcus species, P.abyssi, P.furiosus and P.horikoshii,
      were compared at the DNA level, taking advantage of our identification of their
      replication origins. Three types of rearrangements have been identified: (i)
      inversion and translation across the replication axis (origin/terminus), (ii)
      inversion and translocation restricted to a replichore (the half chromosome
      divided by the replication axis) and (iii) apparent mobility of long clusters of
      repeated sequences. Rearrangements restricted within a replichore were more
      common between P.furiosus and the two other Pyrococcus species than between
      P.horikoshii and P.abyssi. A strong correlation was found between 23 homologous
      insertion sequence elements, present only in P.furiosus, and recombined segment
      boundaries, suggesting that transposition events have been a major cause of
      genomic disruption in this species. Moreover, gene orientation bias was much more
      disrupted than strand composition biases in fragments that switched their
      orientation within a replichore upon recombination. This allowed us to conclude
      that one reversion and one translation occurred in P.abyssi after its divergence
      from P.horikoshii, and that a smaller segment has specifically recombined in
      P.furiosus. Whereas a majority of genes are transcribed in the same direction as
      DNA replication in P.horikoshii and P.abyssi, the colinearity of transcription
      and replication is only maintained for highly transcribed genes in P.furiosus. We
      discuss the implications of genomic rearrangements on gene orientation and
      composition biases, and their consequences on sequence evolution.

PMID- 11972327
TI  - Design of antisense oligonucleotides stabilized by locked nucleic acids.
AB  - The design of antisense oligonucleotides containing locked nucleic acids (LNA)
      was optimized and compared to intensively studied DNA oligonucleotides,
      phosphorothioates and 2'-O-methyl gapmers. In contradiction to the literature, a
      stretch of seven or eight DNA monomers in the center of a chimeric DNA/LNA
      oligonucleotide is necessary for full activation of RNase H to cleave the target
      RNA. For 2'-O-methyl gapmers a stretch of six DNA monomers is sufficient to
      recruit RNase H. Compared to the 18mer DNA the oligonucleotides containing LNA
      have an increased melting temperature of 1.5-4 degrees C per LNA depending on the
      positions of the modified residues. 2'-O-methyl nucleotides increase the T(m) by
      only <1 degree C per modification and the T(m) of the phosphorothioate is
      reduced. The efficiency of an oligonucleotide in supporting RNase H cleavage
      correlates with its affinity for the target RNA, i.e. LNA > 2'-O-methyl > DNA >
      phosphorothioate. Three LNAs at each end of the oligonucleotide are sufficient to
      stabilize the oligonucleotide in human serum 10-fold compared to an unmodified
      oligodeoxynucleotide (from t(1/2) = approximately 1.5 h to t(1/2) = approximately
      15 h). These chimeric LNA/DNA oligonucleotides are more stable than isosequential
      phosphorothioates and 2'-O-methyl gapmers, which have half-lives of 10 and 12 h,
      respectively.

PMID- 11972328
TI  - S6 phosphorylation-independent pathways regulate translation of 5'-terminal
      oligopyrimidine tract-containing mRNAs in differentiating hematopoietic cells.
AB  - Synthesis of new ribosomes is an energy costly and thus highly regulated process.
      Ribosomal protein synthesis is controlled by regulating translation of the
      corresponding ribosomal protein (rp)mRNAs. In mammalian cells a 5'-terminal
      oligopyrimidine tract (TOP) is a conserved feature of these mRNAs that has been
      demonstrated to be essential for their translational regulation. Translation of
      TOP mRNAs has been proposed to be regulated by phosphorylation of ribosomal
      protein S6, which is a common effect of mitogenic stimulation of cells. However,
      as demonstrated here, S6 phosphorylation is not detectable in murine
      erythroleukemia (MEL) or other hematopoietic cells. The absence of S6
      phosphorylation appears to be due to the action of a phosphatase that acts
      downstream of S6 kinase, presumably on S6 itself. Despite the absence of changes
      in S6 phosphorylation, translation of TOP mRNAs is repressed during
      differentiation of MEL cells. These data demonstrate the existence of a mechanism
      for regulating S6 phosphorylation that is distinct from kinase activation, as
      well as the existence of mechanisms for regulating translation of TOP mRNAs that
      are independent of S6 phosphorylation.

PMID- 11972329
TI  - Modulation of mitochondrial transcription in response to mtDNA depletion and
      repletion in HeLa cells.
AB  - The steady-state amounts of mitochondrial transcripts and transcription proteins
      were analyzed during mtDNA depletion and subsequent repletion to gain insight
      into the regulation of human mitochondrial gene expression. As documented
      previously, HeLa cells depleted of mtDNA via treatment with ethidium bromide (EB)
      were found to contain reduced steady-state levels of the mitochondrial
      transcription factor h-mtTFA. When partially mtDNA-depleted cells were cultured
      in the absence of EB, h-mtTFA recovered to normal levels at a significantly
      slower rate than mtDNA. Human mtRNA polymerase exhibited a similar depletion
      repletion profile, suggesting that the mitochondrial transcription machinery is
      coordinately regulated in response to changes in mtDNA copy number. Newly
      synthesized mitochondrial transcripts were detected early in the recovery phase,
      despite the fact that mtDNA, h-mtTFA and h-mtRNA polymerase were simultaneously
      depleted. Although delayed relative to mtDNA, the amounts of h-mtTFA and h-mtRNA
      polymerase sharply increased during the later stages of the recovery phase, which
      was accompanied by accelerated rates of transcription and mtDNA replication.
      Altogether, these data indicate that when mtDNA copy number is low, it is
      beneficial to prevent accumulation of mitochondrial transcription proteins. In
      addition, h-mtTFA and h-mtRNA polymerase are either normally present in excess of
      the amount required for transcription or their activity is up-regulated to ensure
      continued expression and transcription-dependent replication of the mitochondrial
      genome during mtDNA-depleted states.

PMID- 11972330
TI  - Two self-splicing group I introns in the ribonucleotide reductase large subunit
      gene of Staphylococcus aureus phage Twort.
AB  - We have recently described three group I introns inserted into a single gene,
      orf142, of the staphylococcal bacteriophage Twort and suggested the presence of
      at least two additional self-splicing introns in this phage genome. Here we
      report that two previously uncharacterized introns, 429 and 1087 nt in length,
      interrupt the Twort gene coding for the large subunit of ribonucleotide reductase
      (nrdE). Reverse transcription-polymerase chain reaction (RT-PCR) of RNA isolated
      from Staphylococcus aureus after phage infection indicates that the introns are
      removed from the primary transcript in vivo. Both nrdE introns show sequence
      similarity to the Twort orf142 introns I2 and I3, suggesting either a common
      origin of these introns or shuffling of intron structural elements. Intron 2
      encodes a DNA endonuclease, I-TwoI, with similarity to homing endonucleases of
      the HNH family. Like I-HmuI and I-HmuII, intron-encoded HNH endonucleases in
      Bacillus subtilis phages SPO1 and SP82, I-TwoI nicks only one strand of its DNA
      recognition sequence. However, whereas I-HmuI and I-HmuII cleave the template
      strand in exon 2, I-TwoI cleaves the coding strand in exon 1. In each case, the
      3' OH created on the cut strand is positioned to prime DNA synthesis towards the
      intron, suggesting that this reaction contributes to the mechanism of intron
      homing. Both nrdE introns are inserted in highly conserved regions of the
      ribonucleotide reductase gene, next to codons for functionally important
      residues.

PMID- 11972332
TI  - Identification of histone H4-like TAF in Schizosaccharomyces pombe as a protein
      that interacts with WD repeat-containing TAF.
AB  - The general transcription factor TFIID consists of the TATA-binding protein (TBP)
      and multiple TBP-associated factors (TAFs). We previously identified two distinct
      WD repeat-containing TAFs, spTAF72 and spTAF73, in the fission yeast
      Schizosaccharomyces pombe. Here we report the identification of another S.pombe
      TAF, spTAF50, which is the S.pombe homolog of histone H4-like TAFs such as human
      TAF80, Drosophila TAF60 and Saccharomyces cerevisiae TAF60. spTAF50 was
      identified in a two-hybrid screen as a protein that interacts with the C-terminal
      WD repeat-containing region of spTAF72. Gene disruption revealed that spTAF50 is
      essential for cell viability. In vitro, spTAF50 bound to spTAF72 but less
      efficiently to spTAF73. In S.pombe cells, spTAF50 was detected as a protein with
      an apparent molecular mass of approximately 50 kDa. Immunoprecipitation
      experiments demonstrated that spTAF50 is present in both the TFIID and SAGA-like
      complexes as in the case of spTAF72. These results indicate that the C-terminal
      region of spTAF72, which largely consists of WD repeats, interacts with spTAF50
      in the TFIID and SAGA-like complexes, suggesting a role for the WD repeat domain
      in the interaction between TAFs.

PMID- 11972331
TI  - Control of IL-2Ralpha gene expression: structural changes within the proximal
      enhancer/core promoter during T-cell development.
AB  - During T-cell development in thymus, CD25, the IL-2 receptor alpha chain (IL
      2Ralpha) is already expressed in early double-negative (DN) thymocytes where
      commitment to T-cell lineage has been established, but subsequently IL-2Ralpha is
      dramatically down-regulated for the remainder of T-cell development. The loss of
      IL-2Ralpha expression after expression of the pre-TCR alpha:beta complex on the
      cell surface is essential for the later specific responses of mature T cells.
      Using appropriate mouse models and DMS genomic footprinting, we showed that the
      TATA box in the core promoter region of the murine IL-2Ralpha locus was occupied
      only in DN CD25+ T cells. Further, by chromatin immunoprecipitation assays, we
      evidenced that down-regulation of IL-2Ralpha transcription correlated with (i)
      loss of the basal transcriptional machinery; (ii) dissociation of histone
      acetylase p300 and BRG1, a member of the ATP-dependent chromatin remodeling
      complex SWI/SNF; and (iii) histone N-termini dephosphorylation plus
      deacetylation. In contrast, occupancy of the proximal enhancer region (positive
      regulatory region I) was not detected by in vivo genomic footprinting though
      constitutive accessibility of the promoter region for DNase I digestion both in
      the DN and double-positive stages correlated with the constitutive association of
      CBP and PCAF to the IL-2Ralpha core promoter. These results exemplify one
      mechanism by which a promoter enables transcription to switch on and off during T
      cell differentiation.

PMID- 11972333
TI  - Phosphorylation of mismatch repair proteins MSH2 and MSH6 affecting MutSalpha
      mismatch-binding activity.
AB  - Mismatch repair (MMR) is involved in the removal of mispaired bases from DNA and
      thus plays an important role in the maintenance of genomic stability and the
      prevention of mutations and cancer. Moreover, MMR triggers genotoxicity and
      apoptosis upon processing of DNA lesions such as O6-methylguanine. Whereas the
      enzymology of MMR has been elucidated in great detail, only limited data are
      available concerning its regulation. Here we show that the major mismatch-binding
      proteins MSH2 and MSH6, forming the MutSalpha complex, are phosphorylated in
      vitro by protein kinase C and casein kinase II, but not by protein kinase A.
      Phosphorylation of MSH2 and MSH6 was also found within the cell, with MSH6 being
      more extensively phosphorylated than MSH2. Lack of MSH2 and MSH6 phosphorylation
      in vivo due to phosphate depletion, kinase inhibition (by H7 and quercetin) and
      treatment with phosphatases (CIP, SAP and lambda-PPase) significantly reduced
      mismatch-binding activity of MutSalpha. It also prevented methylation-induced
      nuclear translocation of the repair complex, indicating that nuclear
      translocation of MutSalpha upon mutagen treatment is dependent on protein
      phosphorylation. The finding that MSH2 and MSH6 are subject to phosphorylation
      resulting in increased mismatch binding by MutSalpha indicates a novel type of
      post-translational regulation of MMR which might be involved in the response of
      cells to genotoxic stress.

PMID- 11972334
TI  - A single cell cycle genes homology region (CHR) controls cell cycle-dependent
      transcription of the cdc25C phosphatase gene and is able to cooperate with E2F or
      Sp1/3 sites.
AB  - The cdc25C phosphatase participates in regulating transition from the G2 phase of
      the cell cycle to mitosis by dephosphorylating cyclin-dependent kinase 1. The
      tumor suppressor p53 down-regulates expression of cdc25C as part of G2/M
      checkpoint control. Transcription of cdc25C oscillates during the cell cycle with
      no expression in resting cells and maximum transcription in G2. We had identified
      earlier a new mechanism of cell cycle-dependent transcription that is regulated
      by a cell cycle-dependent element (CDE) in conjunction with a cell cycle genes
      homology region (CHR). The human cdc25C gene was the first example. CDE/CHR
      tandem elements have since been found in promoters of many cell cycle genes. Here
      we show that the mouse cdc25C gene is regulated by a CHR but does not hold a CDE.
      Therefore, it is the first identified gene with CHR-dependent transcriptional
      regulation during the cell cycle not relying on a CDE located upstream of it. The
      CHR leads to repression of cdc25C transcription early in the cell cycle and
      directs a release of this repression in G2. Furthermore, we find that this CHR
      can cooperate in cell cycle-dependent transcription with elements placed directly
      upstream of it binding E2F, Sp1 or Sp3 transcription factors.

PMID- 11972335
TI  - Purification and characterization of transcription factor IIIA from Acanthamoeba
      castellanii.
AB  - TFIIIA is required to activate RNA polymerase III transcription from 5S RNA
      genes. Although all known TFIIIA homologs harbor nine zinc fingers that mediate
      DNA binding, very limited sequence homology is found among these proteins, which
      reflects unique properties of some TFIIIA homologs. For example, the Acanthamoeba
      castellanii homolog directly regulates 5S RNA transcription. We have purified and
      characterized A.castellanii TFIIIA (AcTFIIIA) as a step toward obtaining a
      clearer understanding of these differences and of the regulatory process.
      AcTFIIIA is 59 kDa, significantly larger than all other TFIIIA homologs isolated
      to date. Nevertheless, it exhibits a DNase I footprint very similar to those
      produced by the smaller vertebrate TFIIIA homologs, but distinct from the smaller
      footprint of the 51 kDa TFIIIA from Saccharomyces cerevisiae. Similar
      footprinting is not reflected in greater sequence similarity between the
      A.castellanii and vertebrate promoters.

PMID- 11972336
TI  - Insertions in the anticodon loop of tRNA1Gln(sufG) and tRNA(Lys) promote
      quadruplet decoding of CAAA.
AB  - Base insertion mutations in the anticodons of two different Escherichia coli
      tRNAs have been isolated that allow suppression of a series of +1 frameshift
      mutations. Insertion of a U between positions 34 and 35 of tRNAGln1 or addition
      of a G between positions 36 and 37 of tRNA(Lys) expand the anticodons of both
      tRNAs similarly to 3'-GUUU(-5') and allow decoding of complementary 5'-CAAA(-3')
      quadruplets. Analysis of the suppressed mRNA sequences suggests that suppression
      occurs by pairing of the expanded anticodons to all four bases of the
      complementary, quadruplet codon. The tRNA Gln mutants are identical to the sufG
      class of frameshift suppressors isolated both in Salmonella enterica serovar
      Typhimurium and E. coli by Kohno and Roth and previously thought to affect
      tRNA(Lys).

PMID- 11972337
TI  - The p53-induced mouse zinc finger protein wig-1 binds double-stranded RNA with
      high affinity.
AB  - The p53-induced mouse wig-1 gene encodes a Cys2His2-type zinc finger protein of
      unknown function. The zinc fingers in wig-1 are connected by long (56-75) amino
      acid linkers. This distribution of zinc finger domains resembles that of the
      previously described double-stranded (ds)RNA-binding proteins dsRBP-ZFa and JAZ.
      Ectopically expressed FLAG-tagged mouse wig-1 protein localized to nuclei and in
      some cells to nucleoli, whereas GFP-tagged mouse wig-1 localized primarily to
      nucleoli. Electrophoretic mobility shift assay using a recombinant GST-wig-1
      fusion protein showed that wig-1 preferentially binds dsRNA rather than single
      stranded RNA or dsDNA. A set of deletion/truncation mutants of wig-1 was tested
      to determine the dsRNA-binding domain(s) or region(s) in wig-1 that is involved
      in the stabilization of wig-1-dsRNA complexes in vitro. This revealed that the
      first zinc finger in wig-1 is essential for binding to dsRNA, whereas zinc
      fingers 2 and 3 are dispensable. wig-1 protein expressed in mammalian cells also
      showed a high affinity for dsRNA. wig-1 represents the first confirmed p53
      induced gene that encodes a dsRNA-binding protein. This suggests that dsRNA
      binding plays a role in the p53-dependent stress response.

PMID- 11972338
TI  - Heterogeneity in the rate and pattern of germline mutation at individual
      microsatellite loci.
AB  - There is a lack of information on how individual microsatellite loci differ with
      respect to their mutation properties. Such variation will have an important
      bearing on our understanding of the ubiquitous occurrence of simple repeat
      sequences in eukaryotic genomes and on deriving proper mutation models that can
      be incorporated into genetic distance estimates. We genotyped approximately 100
      families of the bird barn swallow (Hirundo rustica) for two hypervariable
      (heterozygosity >95%) microsatellite markers: HrU6, an (AAAG)n tetranucleotide
      repeat, and HrU10, an (AAGAG)n pentanucleotide repeat. A total of 27 germline
      mutation events were documented, corresponding to mutation rates of 0.57% (HrU6)
      and 1.56% (HrU10). The mutation rate increased with allele size, at approximately
      0.1% per repeat unit over the observed range of allele sizes (approximately 10
      100 repeat units). Single repeat unit changes dominated, with 21/27 mutations
      representing the gain or loss of one repeat unit. There was no clear difference
      in the number of gains versus losses nor was there an effect of allele size on
      the magnitude or direction of mutation. Unexpectedly, the mutation rate of
      females (maternally transmitted mutations) was 2.5-5 times higher than that of
      males. Contrasting these observations with mutation data from other
      microsatellite loci reveals differences not only in the mutation rate, but also
      in the magnitude, direction and effect of sex on mutation. Thus, microsatellite
      mutation and evolution may be viewed as a dynamic and variable process.

PMID- 11972339
TI  - Release of replication termination controls mitochondrial DNA copy number after
      depletion with 2',3'-dideoxycytidine.
AB  - Although cellular mitochondrial DNA (mtDNA) copy number varies widely among cell
      lines and tissues, little is known about the mechanism of mtDNA copy number
      control. Most nascent replication strands from the leading, heavy-strand origin
      (O(H)) are prematurely terminated, defining the 3' boundary of the displacement
      loop (D-loop). We have depleted mouse LA9 cell mtDNA to approximately 20% of
      normal levels by treating with 2',3'-dideoxycytidine (ddC) and subsequently
      allowed recovery to normal levels of mtDNA. A quantitative ligation-mediated PCR
      assay was used to determine the levels of both terminated and extended nascent
      O(H) strands during mtDNA depletion and repopulation. Depleting mtDNA leads to a
      release of replication termination until mtDNA copy number approaches a normal
      level. Detectable total nascent strands per mtDNA genome remain below normal.
      Therefore, it is likely that the level of replication termination plays a
      significant role in copy number regulation in this system. However, termination
      of D-loop strand synthesis is persistent, indicating formation of the D-loop
      structure has a purpose that is required under conditions of rapid recovery of
      depleted mtDNA.

PMID- 11972341
TI  - Two-piece tmRNA in cyanobacteria and its structural analysis.
AB  - tmRNA acts to rescue stalled bacterial ribosomes while encoding a peptide tag
      added trans-translationally to the nascent peptide, targeting it for proteolysis.
      The permuted gene structure found in a group of cyanobacteria is shown to produce
      a two-piece mature tmRNA, as had been observed previously for the independently
      permuted gene of alpha-proteobacteria. The pieces have been mapped onto the gene
      sequence and aligned for the permuted cyanobacterial tmRNA sequences, including
      four novel sequences. Structural probing and base pair co-variations support a
      secondary structure model in which two pairings in the tRNA-like domain hold the
      two pieces together, and the coding piece bearing the tag reading frame
      additionally contains a single transient pseudoknot and three other stem-loops.
      This represents a dramatic reduction in pseudoknot number from the five present
      in one-piece cyanobacterial tmRNA.

PMID- 11972340
TI  - Predominance of six different hexanucleotide recoding signals 3' of read-through
      stop codons.
AB  - Redefinition of UAG, UAA and UGA to specify a standard amino acid occurs in
      response to recoding signals present in a minority of mRNAs. This 'read-through'
      is in competition with termination and is utilized for gene expression. One of
      the recoding signals known to stimulate read-through is a hexanucleotide sequence
      of the form CARYYA 3' adjacent to the stop codon. The present work finds that of
      the 91 unique viral sequences annotated as read-through, 90% had one of six of
      the 64 possible codons immediately 3' of the read-through stop codon. The
      relative efficiency of these read-through contexts in mammalian tissue culture
      cells has been determined using a dual luciferase fusion reporter. The relative
      importance of the identity of several individual nucleotides in the different
      hexanucleotides is complex.

PMID- 11972342
TI  - Descent of a split RNA.
AB  - tmRNA is found in the usual one-piece form in most cyanobacteria, but a small
      clade has an unusual two-piece form, resulting from processing of a circularly
      permuted precursor RNA. Here, the secondary structure of the cyanobacterial one
      piece tmRNA is established by phylogenetic sequence comparison; it deviates from
      most tmRNAs in having an extra (fifth) pseudoknot and a branched structure at the
      end of the tag reading frame. Patterns of sequence conservation between the two
      cyanobacterial tmRNA types suggest particular events in the evolution of the two
      piece form. A simple gene permutation model of tandem duplication followed by
      loss of the outermost segments appears inadequate. An additional rearrangement is
      proposed, in which a structure impaired by deletion was regenerated at the
      expense of a neighboring structure.

PMID- 11972343
TI  - Genomic repeats, genome plasticity and the dynamics of Mycoplasma evolution.
AB  - Mycoplasmas evolved by a drastic reduction in genome size, but their genomes
      contain numerous repeated sequences with important roles in their evolution. We
      have established a bioinformatic strategy to detect the major recombination hot
      spots in the genomes of Mycoplasma pneumoniae, Mycoplasma genitalium, Ureaplasma
      urealyticum and Mycoplasma pulmonis. This allowed the identification of large
      numbers of potentially variable regions, as well as a comparison of the relative
      recombination potentials of different genomic regions. Different trends are
      perceptible among mycoplasmas, probably due to different functional and
      structural constraints. The largest potential for illegitimate recombination in
      M.pulmonis is found at the vsa locus and its comparison in two different strains
      reveals numerous changes since divergence. On the other hand, the main
      M.pneumoniae and M.genitalium adhesins rely on large distant repeats and, hence,
      homologous recombination for variation. However, the relation between the
      existence of repeats and antigenic variation is not necessarily straightforward,
      since repeats of P1 adhesin were found to be anti-correlated with epitopes
      recognized by patient antibodies. These different strategies have important
      consequences for the structures of genomes, since large distant repeats correlate
      well with the major chromosomal rearrangements. Probably to avoid such events,
      mycoplasmas strongly avoid inverse repeats, in comparison to co-oriented repeats.

PMID- 11972345
TI  - CopR binds and bends its target DNA: a footprinting and fluorescence resonance
      energy transfer study.
AB  - Plasmid pIP501 encoded transcriptional repressor CopR is one of the two
      regulators of plasmid copy number. Previous data suggested that CopR is a HTH
      protein belonging to a family of 578 HTH proteins (termed HTH 3-family). Only a
      very limited number of proteins in this family, among them lambda c1 repressor,
      434 c1 repressor and P22 c2 repressor, have been characterized in detail so far.
      Previously, a CopR structural model was built based on structural homologies to
      the 434 c1 and P22 c2 repressor and used to identify amino acids involved in DNA
      binding and dimerization. Site-directed mutagenesis in combination with
      electrophoretic mobility shift assay (EMSA), dimerization studies and circular
      dichroism (CD) measurements verified the model predictions. In this study we used
      hydroxyl radical footprinting and fluorescence resonance energy transfer (FRET)
      measurements to obtain detailed information about the structure of the DNA in the
      CopR-DNA complex. Our results show that the DNA is bent gently around the
      protein, comparable to the bending angle of 20-25 degrees observed in the 434 c1
      repressor-DNA complex and the lambda c1 repressor-DNA complex. The shape of CopR
      dimers as determined by sedimentation velocity experiments is extended and
      accounts for the relatively large area of protection observed with hydroxyl
      radical footprinting.

PMID- 11972344
TI  - Characterization of PREP2, a paralog of PREP1, which defines a novel sub-family
      of the MEINOX TALE homeodomain transcription factors.
AB  - TALE (three amino acid loop extension) homeodomain proteins include the PBC and
      the MEINOX sub-families. MEINOX proteins form heterodimer complexes with PBC
      proteins. Heterodimerization is crucial to DNA binding and for nuclear
      localization. PBC-MEINOX heterodimers bind DNA also in combination with HOX
      proteins, thereby modulating their DNA-binding specificity. TALE proteins
      therefore play crucial roles in multiple developmental and differentiation
      pathways in vivo. We report the identification and characterization of a novel
      human gene homologous to PREP1, called PREP2. Sequence comparisons indicate that
      PREP1 and PREP2 define a novel sub-family of MEINOX proteins, distinct from the
      MEIS sub-family. PREP2 is expressed in a variety of human adult tissues and
      displays a more restricted expression pattern than PREP1. PREP2 is capable of
      heterodimerizing with PBC proteins. Heterodimerization with PBX1 appears to be
      essential for nuclear localization of both PREP2 and PBX1. A comparison between
      the functional properties of PREP1 and PREP2 reveals that PREP2-PBX display a
      faster DNA-dissociation rate than PREP1-PBX heterodimers, suggesting different
      roles in controlling gene expression. Like PREP1, PREP2-PBX heterodimers are
      capable of forming ternary complexes with HOXB1. The analysis of some PREP2 in
      vitro properties suggests a functional diversification among PREP and between
      PREP and MEIS MEINOX proteins.

PMID- 11972346
TI  - Human DNA polymerase mu (Pol mu) exhibits an unusual replication slippage ability
      at AAF lesion.
AB  - We analyzed the ability of various cell extracts to extend a radiolabeled primer
      past an N-2-acetylaminofluorene (AAF) adduct located on a primed single-stranded
      template. When the 3' end of the primer is located opposite the lesion, partially
      fractionated human primary fibroblast extracts efficiently catalyzed primer
      terminus extension by adding a ladder of about 15 dGMPs, in an apparently non
      templated reaction. This activity was not detected in SV40-transformed
      fibroblasts or in HeLa cell extracts unless purified human DNA polymerase mu (Pol
      mu) was added. In contrast, purified human Pol mu alone could only add three
      dGMPs as predicted from the sequence of the template. These results suggest that
      a cofactor(s) present in cellular extracts modifies Pol mu activity. The
      production of the dGMP ladder at the primer terminus located opposite the AAF
      adduct reveals an unusual ability of Pol mu (in conjunction with its cofactor) to
      perform DNA synthesis from a slipped intermediate containing several unpaired
      bases.

PMID- 11972347
TI  - Functional characterization of the interferon regulatory element in the enhancer
      1 region of the hepatitis B virus genome.
AB  - An interferon-stimulated response element (ISRE)/interferon regulatory element
      (IRE) spanning nucleotide coordinates 1091-1100 is present in the enhancer 1/X
      gene promoter region of the hepatitis B virus (HBV) genome. In the context of a
      minimal promoter element, the enhancer 1/X gene promoter ISRE/IRE was shown to be
      a functional regulatory site capable of mediating interferon alpha- (IFNalpha)
      and interferon-stimulated gene factor 3 (ISGF3)-specific transcriptional
      activation in transient transfection analysis. The enhancer 1/X gene promoter
      ISRE/IRE was also shown to mediate interferon regulatory factor (IRF) 1 and IRF7
      activation of transcription from a minimal promoter construct. In contrast,
      IFNalpha and the IRFs had minimal effect on HBV transcription and replication in
      the context of the viral genome in cell culture.

PMID- 11972348
TI  - Searching for RNA genes using base-composition statistics.
AB  - The hypothesis that genomic regions rich in non-protein-coding RNAs (ncRNAs) can
      be identified using local variations in single-base and dinucleotide statistics
      has been investigated. (G+C)%, (G-C)% difference, (A-T)% difference and
      dinucleotide-frequency statistics were compared among seven classes of ncRNAs and
      three genomes. Significant variations were observed in (G+C)% and, in
      Methanococcus jannaschii, in the frequency of the dinucleotide 'CG'. Screening
      programs based on these two base-composition statistics were developed. With
      (G+C)% screening alone, a 1% fraction of the M.jannaschii genome containing all
      44 known transfer RNAs, ribosomal RNAs and signal recognition particle RNAs could
      be identified. When (G+C)% combined with CG dinucleotide-frequency screening was
      used, 43 of the 44 known M.jannaschii structural ncRNAs were again identified,
      while the number of presumably false hits overlapping a known or putative protein
      coding gene was reduced from 15 to 6. In addition, 19 candidate ncRNAs were
      identified including one with significant homology to several known archaeal
      RNaseP RNAs.

PMID- 11972349
TI  - Heteroduplexes in mixed-template amplifications: formation, consequence and
      elimination by 'reconditioning PCR'.
AB  - Although it has been recognized that PCR amplification of mixed templates may
      generate sequence artifacts, the mechanisms of their formation, frequency and
      potential elimination have not been fully elucidated. Here evidence is presented
      for heteroduplexes as a major source of artifacts in mixed-template PCR. Nearly
      equal proportions of homoduplexes and heteroduplexes were observed after co
      amplifying 16S rDNA from three bacterial genomes and analyzing products by
      constant denaturing capillary electrophoresis (CDCE). Heteroduplexes became
      increasingly prevalent as primers became limiting and/or template diversity was
      increased. A model exploring the fate of cloned heteroduplexes during MutHLS
      mediated mismatch repair in the Escherichia coli host demonstrates that the
      diversity of artifactual sequences increases exponentially with the number of
      both variable nucleotides and of original sequence variants. Our model
      illustrates how minimization of heteroduplex molecules before cloning may reduce
      artificial genetic diversity detected during sequence analysis by clone
      screening. Thus, we developed a method to eliminate heteroduplexes from mixed
      template PCR products by subjecting them to 'reconditioning PCR', a low cycle
      number re-amplification of a 10-fold diluted mixed-template PCR product. This
      simple modification to the protocol may ensure that sequence richness encountered
      in clone libraries more closely reflects genetic diversity in the original
      sample.

PMID- 11972350
TI  - Effect of primary and secondary structure of oligodeoxyribonucleotides on the
      fluorescent properties of conjugated dyes.
AB  - We studied fluorescence intensity, polarization and lifetime of some commonly
      used fluorophores conjugated to oligodeoxyribonucleotides with different primary
      and secondary structures. We found that fluorescence intensity can increase or
      decrease upon hybridization of the labeled strand to its complement depending on
      the sequence and position of the fluorophore. Up to 10-fold quenching of the
      fluorescence upon hybridization was observed when the dye moiety was attached
      close to the 3' end and the 3'-terminal base was either dG or dC. No quenching
      upon hybridization was observed when the dye was positioned within the same
      sequence context but close to the 5' end. The presence of a dG overhang quenches
      the fluorescence less efficiently than a blunt end dG-dC or dC-dG base pair. When
      located internally in the double strand, the dG-dC base pair does not affect the
      fluorescence of the nearby dye. Guanosine in a single-stranded oligonucleotide
      quenches the fluorescence of nearby dye by <2-fold. Upon duplex formation, this
      quenching is eliminated and the fluorescence increases. This increase can only be
      detected when the fluorophore is located at least 6 nt from the terminal dG-dC
      base pair. The change of fluorescence polarization upon duplex formation
      inversely correlates with the change of intensity. Fluorescein conjugated to a
      single-stranded oligonucleotide or a duplex undergoes a bi-exponential decay with
      approximately 4 and approximately 1 ns lifetimes.

PMID- 11972351
TI  - Relative expression software tool (REST) for group-wise comparison and
      statistical analysis of relative expression results in real-time PCR.
AB  - Real-time reverse transcription followed by polymerase chain reaction (RT-PCR) is
      the most suitable method for the detection and quantification of mRNA. It offers
      high sensitivity, good reproducibility and a wide quantification range. Today,
      relative expression is increasingly used, where the expression of a target gene
      is standardised by a non-regulated reference gene. Several mathematical
      algorithms have been developed to compute an expression ratio, based on real-time
      PCR efficiency and the crossing point deviation of an unknown sample versus a
      control. But all published equations and available models for the calculation of
      relative expression ratio allow only for the determination of a single
      transcription difference between one control and one sample. Therefore a new
      software tool was established, named REST (relative expression software tool),
      which compares two groups, with up to 16 data points in a sample and 16 in a
      control group, for reference and up to four target genes. The mathematical model
      used is based on the PCR efficiencies and the mean crossing point deviation
      between the sample and control group. Subsequently, the expression ratio results
      of the four investigated transcripts are tested for significance by a
      randomisation test. Herein, development and application of REST is explained and
      the usefulness of relative expression in real-time PCR using REST is discussed.
      The latest software version of REST and examples for the correct use can be
      downloaded at http://www.wzw.tum.de/gene-quantification/.

PMID- 11972352
TI  - Multiplex quantitative PCR using self-quenched primers labeled with a single
      fluorophore.
AB  - Multiplex quantitative PCR based on novel design of fluorescent primers is
      described. Fluorogenic primers are labeled with a single fluorophore on a base
      close to the 3' end with no quencher required. A tail of 5-7 nt is added to the
      5' end of the primer to form a blunt-end hairpin when the primer is not
      incorporated into a PCR product. This design provides a low initial fluorescence
      of the primers that increases up to 8-fold upon formation of the PCR product. The
      hairpin oligonucleotides (DeltaG from -1.6 to -5.8 kcal/mol) may be as efficient
      as linear primers and provide additional specificity to the PCR by preventing
      primer-dimers and mispriming. Multiple fluorogenic primers were designed by
      specialized software and used for real-time quantitation of c-myc and IL-4 cDNAs
      in the presence of reference genes such as beta-actin, GAPDH and 18S rRNA.
      Targets of 10-10(7) copies were detected with precision in PCR using FAM-labeled
      primers for variable genes and JOE-labeled primers for the reference genes. This
      method was also used to detect single nucleotide polymorphism of the human
      retinal degeneration gene by allele-specific PCR with end-point detection using a
      fluorescent plate reader or a UV-transilluminator. We conclude that fluorogenic
      mono-labeled primers are an efficient and cost-effective alternative to FRET
      labeled oligonucleotides.

PMID- 11972354
TI  - High throughput measurement of duplex, triplex and quadruplex melting curves
      using molecular beacons and a LightCycler.
AB  - We have used oligonucleotides containing molecular beacons to determine melting
      profiles for intramolecular DNA duplexes, triplexes and quadruplexes
      (tetraplexes). The synthetic oligonucleotides used in these studies contain a
      fluorophore (fluorescein) and quencher (methyl red) attached either to
      deoxyribose or to the 5 position of dU. In the folded DNA structures the
      fluorophore and quencher are in close proximity and the fluorescence is quenched.
      When the structures melt, the fluorophore and quencher are separated and there is
      a large increase in fluorescence. These experiments were performed in a Roche
      LightCycler; this requires small amounts of material (typically 4 pmol
      oligonucleotide) and can perform 32 melting profiles in parallel. We have used
      this technique to compare the stability of triplexes containing different base
      analogues and to confirm the selectivity of a triplex-binding ligand for triplex,
      rather than duplex, DNA. We have also compared the melting of inter- and
      intramolecular quadruplexes.

PMID- 11972355
TI  - A novel strategy for the functional cloning of enzymes using filamentous phage
      display: the case of nucleotidyl transferases.
AB  - In vitro selections for catalytic activity have been designed for the isolation
      of genes encoding enzymes from libraries of proteins displayed on filamentous
      phages. The proteins are generally expressed as C-terminal fusions with the N
      terminus of the minor coat protein p3 for display on phages. As full-length cDNAs
      generally contain several stop codons near their 3' end, this approach cannot be
      used for their expression on the surface of phages. Here we show that in vitro
      selection for catalytic activity is compatible with a system for expression of
      proteins as N-terminal fusions on the surface of bacteriophages. It is
      highlighted for the Stoffel fragment of Taq DNA polymerase I and makes use of (p3
      Jun/Fos-Stoffel fragment) fusions. The efficiency of the selection is measured by
      an enrichment factor found to be about 55 for a phage polymerase versus a phage
      not expressing a polymerase. This approach could provide a method for the
      functional cloning of nucleotidyl transferases from cDNA libraries using
      filamentous phage display.

PMID- 11972356
TI  - CTLA-4 negative signaling via lipid rafts: A new perspective.
AB  - Proper function of the immune system requires that activation of T cells is
      precisely regulated. Responses to the T cell receptor are modulated by signals
      from other receptors. CTLA-4 (cytotoxic T lymphocyte antigen-4, also called
      CD152), for example, inhibits cytokine production and proliferation of T cells.
      Activation of T cells is associated with the accumulation of signaling proteins
      in lipd rafts--microdomains of the plasma membrane enriched in cholesterol and
      glycosphingolipds. Rudd et al. discuss evidence that CTLA-4 might inhibit
      cytokine production and T cell proliferation by limiting the assembly of lipid
      rafts, which are critical to the formation of a functional immunological synapse
      between antigen-presenting cells and T cells.

PMID- 11972357
TI  - Flow cytometric analysis of T cell receptor signal transduction.
AB  - Intracellular assays of signal transduction in T cells stimulated by antigen in
      vivo have been limited by requirements for large numbers of highly purified cells
      to perform conventional biochemical techniques. Here, we describe a technique
      using flow cytometry to study signaling events in T cells after antigen
      recognition in the body.

PMID- 11972358
TI  - Controlling the immune system through semaphorins.
AB  - Semaphorins provide crucial attractive and repulsive cues involved in axon
      guidance. Several semaphorins have also been detected in cells of the immune
      system. Their influence on cell motility has been reported and is reminiscent of
      the biological function attributed to nervous system semaphorins. Receptors of
      the plexin and neuropilin family of proteins, also expressed by some immune
      cells, may be involved in semaphorin signaling in the immune system. However,
      semaphorins also affect the functioning of the immune system through receptors
      regulating lymphocyte activation. An important challenge in the future will be to
      determine whether, as in the nervous system, semaphorins help immune cells to
      establish connections with their appropriate targets.

PMID- 11972359
TI  - Protein lipid overlay assay.
AB  - The Protein Lipid Overlay (PLO) assay enables the identification of the lipid
      ligands with which lipid binding proteins interact. This assay also provides
      qualitative information on the relative affinity with which a protein binds to a
      lipid. In the PLO assay, serial dilutions of different lipids are spotted onto a
      nitrocellulose membrane to which they attach. These membranes are then incubated
      with a lipid binding protein possessing an epitope tag. The membranes are washed
      and the protein, still bound to the membrane by virtue of its interaction with
      lipid(s), is detected by immunoblotting with an antibody recognizing the epitope
      tag. This procedure requires only a few micrograms of protein and is quicker and
      cheaper to perform than other methods that have been developed to assess protein
      lipid interactions. The reagents required for the PLO assay are readily available
      from commercial sources and the assay can be performed in any laboratory, even by
      those with no prior expertise in this area.

PMID- 11972353
TI  - A two-step strategy for constructing specifically self-subtracted cDNA libraries.
AB  - We have developed a new strategy for producing subtracted cDNA libraries that is
      optimized for connective and epithelial tissues, where a few exceptionally
      abundant (super-prevalent) RNA species account for a large fraction of the total
      mRNA mass. Our method consists of a two-step subtraction of the most abundant
      mRNAs: the first step involves a novel use of oligo-directed RNase H digestion to
      lower the concentration of tissue-specific, super-prevalent RNAs. In the second
      step, a highly specific subtraction is achieved through hybridization with probes
      from a 3'-end ESTs collection. By applying this technique in skeletal muscle, we
      have constructed subtracted cDNA libraries that are effectively enriched for
      genes expressed at low levels. We further report on frequent premature
      termination of transcription in human muscle mitochondria and discuss the
      importance of this phenomenon in designing subtractive approaches. The tissue
      specific collections of cDNA clones generated by our method are particularly well
      suited for expression profiling.

PMID- 11972360
TI  - Endocannabinoids and neuroprotection.
AB  - Traumatic brain injury (TBI) releases harmful mediators that lead to secondary
      damage. On the other hand, neuroprotective mediators are also released, and the
      balance between these classes of mediators determines the final outcome after
      injury. Recently, it was shown that the endogenous brain cannabinoids anandamide
      and 2-Arachidonoyl glycerol (2-AG) are also formed after TBI in rat and mouse
      respectively, and when administered after TBI, they reduce brain damage. In the
      case of 2-AG, better results are seen when it is administered together with
      related fatty acid glycerol esters. Significant reduction of brain edema, better
      clinical recovery, and reduced infarct volume and hippocampal cell death are
      noted. This new neuroprotective mechanism may involve inhibition of transmitter
      release and of inflammatory response. 2-AG is also a potent modulator of vascular
      tone, and counteracts the endothelin (ET-1)-induced vasoconstriction that
      aggravates brain damage; it may thus help to restore blood supply to the injured
      brain.

PMID- 11972361
TI  - Present state and perspectives of synchrotron radiation diffraction imaging.
AB  - The modern third-generation synchrotron radiation sources offer enhanced
      possibilities for all variants of imaging techniques. The quantitative and
      qualitative improvements with respect to previous synchrotron diffraction imaging
      work, which include the investigation in transmission of bulky samples, the use,
      as an additional parameter, of the sample-to-detector distance, and the use of
      the coherence of the beam, are illustrated by several examples. Emphasis is given
      to the possibilities associated with modern electronic detectors for this type of
      imaging. The new techniques implemented at the ESRF that take full advantage of
      new capabilities, and more particularly that of 'topo-tomography', are presented.

PMID- 11972363
TI  - Parabolic refractive X-ray lenses.
AB  - Parabolic refractive X-ray lenses are optical components, especially suitable for
      third-generation synchrotron radiation sources. This article describes the status
      of the development of our lenses and illustrates the possibilities for micrometre
      and submicrometre focusing and for X-ray imaging in absorption and phase
      contrast. The parabolic lens profile ensures distortion-free imaging of high
      quality. First characteristics of Be lenses are given. A microscope based on Be
      lenses is expected to have a lateral resolution below 80 nm.

PMID- 11972364
TI  - Zernike-type X-ray imaging microscopy at 25 keV with Fresnel zone plate optics.
AB  - A Zernike-type imaging microscope using a sputtered-sliced Fresnel zone plate (SS
      FZP) has been developed and tested at an X-ray energy of 25 keV. The SS-FZP was
      used as an objective. A copper (Cu) phase plate was placed at the back focal
      plane of the SS-FZP in order to produce phase contrast. The performance of the
      Zernike-type imaging microscope was tested with a gold (Au) mesh and a resolution
      test pattern at undulator beamline 47 of SPring-8. The Au mesh and the resolution
      test pattern could be imaged in transmission with a magnification of x10.2. Owing
      to the Cu phase plate, different image contrast was observed compared with the
      bright-field image contrast. Tantalum microstructures down to 0.5 microm line-and
      space have been observed on spatial resolution test patterns.

PMID- 11972365
TI  - Elemental analysis with a full-field X-ray fluorescence microscope and a CCD
      photon-counting system.
AB  - The first result is presented of an X-ray fluorescence microscope with a Wolter
      mirror in combination with a CCD camera used as an energy-resolved two
      dimensional detector in photon-counting mode. Two-dimensional elemental maps of
      metallic wires, such as Fe, Co, Ni and Cu, and inclusions of a synthesized
      diamond could be obtained with an energy resolution of 350 eV.

PMID- 11972366
TI  - High-resolution hard X-ray phase-contrast microscopy with a large-diameter and
      high-numerical-aperture zone plate.
AB  - An imaging transmission hard X-ray microscope has been constructed at beamline
      BL24XU of SPring-8. It makes use of a phase zone plate made of tantalum with a
      diameter of 1 mm and an outer-most zone width of 50 nm, aiming at a wide field of
      view and a high spatial resolution. The performance test was carried out at a
      photon energy of 10 keV. A field of view as wide as approximately 200 microm in
      diameter was achieved. The spatial resolution was measured to be 220 nm by
      analyzing a knife-edge image. Further, a line-and-space pattern as fine as 100 nm
      could be imaged. By placing a phase plate made of gold in the back focal plane of
      the zone plate, phase-contrast microscopy using Zernike's method was also carried
      out. The feasibility of phase-contrast microscopy for observing transparent
      samples was successfully demonstrated by imaging small polystyrene particles.

PMID- 11972367
TI  - Phase-contrast X-ray imaging based on interferometry.
AB  - Phase-contrast X-ray imaging including tomographic configuration using a crystal
      X-ray interferometer is reviewed. The imaging principle based on phase retrieval
      is described, and some demonstrations showing its high sensitivity are presented
      on the observations of animal and human cancerous tissues.

PMID- 11972368
TI  - Application of synchrotron X-ray imaging to phase objects in orthopedics.
AB  - Novel imaging of the fine structures of the ribs of a pig and a specimen of human
      osteosarcoma utilizing the spatial coherence of X-rays was successfully performed
      with an incident X-ray energy of 30 keV at SPring-8, Japan. The image contrast
      appearing at the periphery of trabecular bone, small calcifications and small
      fractures is caused by the phase shift of the X-rays at the boundary of these
      objects that have different X-ray refractive indices. The image is recorded on
      mammography film without an intensifying screen. Comparison of the image contrast
      using different sample-to-film distances, Z, such as Z = 5 m and Z approximately
      0 m, showed that the former images were always more informative, i.e. better in
      resolution and/or image contrast when imaging trabecular bone, bone marrow and
      small fractures in compact bone, and for imaging cartilage. Radiography using
      synchrotron X-rays for phase objects should be a powerful tool for diagnosis in
      orthopedics, especially for bone disease.

PMID- 11972369
TI  - Quantitative analysis of two-component samples using in-line hard X-ray images.
AB  - Methods for rapid quantitative phase-sensitive X-ray imaging of non-crystalline
      samples consisting of two distinct components are investigated. The transverse
      spatial distribution of the projected thickness of each component is
      reconstructed by computer processing of in-line images collected using
      synchrotron-generated hard X-rays and a position-sensitive detector with
      submicrometre spatial resolution. Different imaging techniques and associated
      image-processing algorithms are considered, with relative advantages and
      difficulties of each approach compared. A possible generalization of the method
      for the case of n-component samples is briefly discussed.

PMID- 11972370
TI  - Development of a multilayer Fresnel zone plate for high-energy synchrotron
      radiation X-rays by DC sputtering deposition.
AB  - Hard X-ray microscopy with high spatial resolution (<or=0.1 microm) using a high
      energy and high-brilliance X-ray microprobe is expected to be a promising
      technology for various types of analysis, imaging etc. in materials science,
      biology and medicine. A multilayer Fresnel zone plate (FZP) could be a promising
      approach to focusing optics in the high-energy X-ray region (>or=20 keV) because
      a large thickness (aspect ratio) can be available. Various types of multilayer
      FZPs have been fabricated by DC sputtering deposition. Their focusing
      characteristics have been evaluated at the high-brilliance undulator beamline
      BL47XU of SPring-8. An optical system using a Cu/Al multilayer FZP (with an
      outermost zone width of 0.25 microm) as the focusing optics fabricated by the
      optimum deposition condition with precise film (zone) thickness control has
      attained an almost diffraction-limited microbeam of 0.3-0.35 microm at 8.9 keV. A
      line-and-space resolution test pattern has been observed: fine structures up to
      0.2 microm were clearly observed in the measured image. This FZP has been working
      since 1995, keeping good focusing characteristics. It can be said from these
      results that a spatial resolution better than 0.1 microm in the high-energy X-ray
      region is in prospect by the development of a multilayer FZP with a narrower
      outermost zone width in the near future.

PMID- 11972371
TI  - X-ray refraction-enhanced imaging and a method for phase retrieval for a simple
      object.
AB  - Refraction-enhanced imaging is now widely used for imaging low-absorption
      contrast specimens in the hard X-ray region. However, the interpretation of the
      details of a refraction-enhanced image is not always clear. In this paper the
      theoretical treatment of refraction-enhanced imaging and a method for phase
      retrieval from refraction-contrast images are discussed in comparison with
      angular-deflection mapping of the transmitting beam. The problems of thick and
      complicated objects are also discussed.

PMID- 11972373
TI  - Plane-wave X-ray topography and its application at SPring-8.
AB  - Plane-wave X-ray topography experiments were carried out at a 200 m-long
      beamline, BL20B2, at SPring-8. Relatively high-energy X-rays of 30 keV with an
      angular divergence of about 0.01 arcsec were produced by using only one
      collimator crystal. FZ-Si and CZ-Si wafers were characterized in transmission
      geometry (Laue case). Clear oscillatory profiles in rocking curves of the FZ-Si
      crystal were observed. Plane-wave topographic images of dislocations, growth
      striations and grown-in microdefects in the CZ-Si crystals were obtained. The
      dependence of the topographic images of the lattice defects on the sample
      photoplate distance was also studied.

PMID- 11972372
TI  - Synchrotron-radiation X-ray topography of surface strain in large-diameter
      silicon wafers.
AB  - Using a 300 mm-wide monochromatic X-ray beam obtained at beamline BL20B2 of
      SPring-8, the difference in surface-strain distribution caused by various steps
      of silicon-wafer manufacturing, i.e. slicing, lapping, etching, grinding and
      polishing, was studied. The asymmetric 511 reflection of 21.45 keV X-rays,
      incident at a glancing angle of 0.26 degrees, was used to obtain topographs over
      the whole surface of a 200 mm-diameter (100) CZ silicon wafer. Differences in
      crystallinity and in warp between the surfaces at different steps of the
      manufacturing process (firstly after the lapping following the slicing, and then
      after successive etching, grinding and polishing) were clearly observed. The
      former gave a topographic image over the whole area with a one-shot exposure
      because of their wide rocking curves (50-70 arcsec FWHM), which indicate poor
      crystallinity. The latter, on the other hand, showed sharper curves (4-5 arcsec
      FWHM), which indicate good crystallinity in local areas, and the existence of
      warp, and therefore required step scanning of omega-rotation to cover the whole
      surface in topography measurements. The effect of each step in the process is
      also discussed.

PMID- 11972374
TI  - Synchrotron X-ray topography of electronic materials.
AB  - Large-area transmission, transmission section, large-area back-reflection, back
      reflection section and grazing-incidence topography are the geometries used when
      recording high-resolution X-ray diffraction images with synchrotron radiation
      from a bending magnet, a wiggler or an undulator of an electron or a positron
      storage ring. Defect contrast can be kinematical, dynamical or orientational even
      in the topographs recorded on the same film at the same time. In this review
      article limited to static topography experiments, examples of defect studies on
      electronic materials cover the range from voids and precipitates in almost
      perfect float-zone and Czochralski silicon, dislocations in gallium arsenide
      grown by the liquid-encapsulated Czochralski technique, the vapour-pressure
      controlled Czochralski technique and the vertical-gradient freeze technique,
      stacking faults and micropipes in silicon carbide to misfit dislocations in
      epitaxic heterostructures. It is shown how synchrotron X-ray topographs of
      epitaxic laterally overgrown gallium arsenide layer structures are successfully
      explained by orientational contrast.

PMID- 11972375
TI  - Zernike-type phase-contrast hard X-ray microscope with a zone plate at the Photon
      Factory.
AB  - A Zernike-type phase-contrast X-ray microscope with a zone plate and a phase
      plate was constructed at the Photon Factory BL3C2. Parallel monochromatic X-rays
      of 8.97 keV were incident on a specimen and a direct beam transmitted through the
      specimen was focused on the back focal plane of the zone plate, where an
      aluminium phase plate was placed. Tantalum line patterns as fine as 0.3 microm
      could be imaged. Phase-contrast images of polypropylene wires and polystyrene
      latex beads were obtained, which showed better contrast than that of their bright
      field images.

PMID- 11972376
TI  - Hard X-ray microbeam experiments with a sputtered-sliced Fresnel zone plate and
      its applications.
AB  - Hard X-ray microbeam experiments with sputtered-sliced Fresnel zone plates have
      been performed. Zone plates with an outermost zone width of 0.25 microm (#FZP1)
      and 0.1 microm (#FZP2) were fabricated and evaluated. In a scanning X-ray
      microscopy experiment, a line-and-space pattern with structure as fine as 0.1
      microm was resolved using #FZP2 at an X-ray wavelength of 1 A. As an application
      of the microbeam technique, a two-dimensional distribution of constituent
      elements in forensic samples has been obtained (e.g. section view of human and
      elephant hairs) using fluorescent scanning microscopy.

PMID- 11972381
TI  - Is there a difference in survival for IA1 and IA2 adenocarcinoma of the uterine
      cervix?
AB  - OBJECTIVE: The goal of this study was to determine if International Federation of
      Obstetrics and Gynecology (FIGO) subdivision into IA1 versus IA2 is predictive of
      survival differences for early invasive adenocarcinoma. METHODS: The
      Surveillance, Epidemiology, and End-Results (SEER) Public-Use Database was used
      to identify all cases of IA1 and IA2 adenocarcinoma diagnosed between 1983 and
      1997. A systematic literature search (MEDLINE 1966-2000) was used to identify all
      previously published cases. Stage, depth of invasion, node status, therapy, and
      survival were analyzed using Fisher's exact and log-rank tests. RESULTS: In SEER,
      560 cases were identified: 200 IA1, 286 IA2, and 74 localized. Simple
      hysterectomy was performed in 272 (48.6%) and radical hysterectomy in 210
      (37.5%). Positive lymph nodes were found in 3 of 197 (1.5%) who underwent
      lymphadenectomy, 2 of whom died. The censored survival by stage (mean follow-up
      51.6 months) was not significantly different (P = 0.77) for IA1 versus IA2 (98.5%
      vs 98.6%). Combining these data with all other published series of early cervical
      adenocarcinoma, 1170 cases were identified, including 585 IA1, 358 IA2, and 227
      "others," with less defined early disease. Of 531 (45.4%) who underwent
      lymphadenectomy, 15 (1.28%) had one or more positive nodes; of these, 11 (73.3%)
      recurred or died. For IA1 versus IA2 disease, there were no significant
      differences in the frequency of positive lymph nodes, recurrence, or death.
      However, "others," those with less well-defined lesions, or larger than IA2, were
      at increased risk. CONCLUSION: Early invasive adenocarcinoma (IA1 and IA2) has an
      excellent prognosis and conservative surgery may be appropriate. Since current
      FIGO staging definitions do not distinguish high- from low-risk disease,
      individualization of therapy based on pathology review, risk assessment, and
      patient preference is recommended.

PMID- 11972382
TI  - Resource utilization for patients undergoing hysterectomy with or without lymph
      node dissection for endometrial cancer.
AB  - OBJECTIVE: The objective was to study the association of age, comorbid illness,
      race, and type of hospital with resource use in patients undergoing hysterectomy
      and lymph node dissection for endometrial cancer. METHODS: The study was a
      population-based analysis of patients undergoing hysterectomy with a diagnosis of
      endometrial cancer in Maryland 1994-1996. Chi-square and t tests determined
      differences in means or proportions. Multivariate logistic regression methods
      were used to build predictive models. RESULTS: The 1281 women underwent total
      abdominal hysterectomy, 91%; total vaginal hysterectomy, 6%; radical
      hysterectomy, 2.5%, laparoscopically assisted total vaginal hysterectomy, 0.3%;
      32% also underwent lymph node dissection. Neither age, nor race, nor comorbid
      illness influenced admission to teaching hospitals. Co-morbidity was documented
      in 56% of cases. African Americans were more likely to have one (P = 0.002) or >1
      co-morbid illness (P = 0.045) than Caucasians. The most common complications were
      anemia (13.6%), infection/fever (12%), cardiac (9.4%), pneumonia (8%), ileus
      (5%), and bowel obstruction (5%). These complications occurred with higher
      frequency in teaching hospitals (P = 0.0001), In large hospitals (P = 0.0001),
      and in African American patients compared to Caucasians (P = 0.028). Multivariate
      regression analysis revealed that older age, admission to teaching or large
      hospitals, lymph node dissection, heart disease, and African American race were
      associated with significantly higher resource use. CONCLUSION: We documented age
      and racial/ethnic differences in comorbid illness, complications, and resource
      utilization for patients undergoing hysterectomy for endometrial cancer. The
      differences in resource use for teaching hospitals may be reflective of the
      severity of complications, which are indirectly determined by length of stay.
      Given the higher costs and skills required to care for elderly women with
      comorbid disease and complications, quantification of the complexity of care is
      of utmost importance for allocation of sufficient resources for the care of women
      with endometrial cancer.

PMID- 11972383
TI  - Recruitment strategies for cervical cancer prevention study.
AB  - OBJECTIVE: The aim of this study was to describe recruitment strategies for a
      single-visit cervical cancer prevention study. METHODS: From January through
      December 1999, low-income, predominantly Latino women were recruited to
      participate in a single-visit cervical cancer prevention study. For the first 6
      months, all women who had ever visited one of two community-based study clinics
      were invited to participate (clinic registry recruitment). For the remainder of
      the year, recruitment was modified to be primarily inclusive of advertisements in
      English- and Spanish-language community newspapers and fliers left in local
      businesses and organizations (media campaign recruitment). Eligible volunteers
      were randomized to one of two study arms, usual-care program or single-visit
      program. All study subjects completed demographic and medical questionnaires
      delivered by bilingual staff. Women who declined to participate in this study
      were asked to provide reasons for this preference. Statistical analyses included
      the use of chi-square, logistic regression, and Student's t test. RESULTS: The
      proportion of women who agreed to participate was higher in the media recruitment
      group than in the clinic registry group [51% (535/1041) compared to 26%
      (405/1542), P < 0.001]. The no-show rate among participants solicited from the
      media strategy was significantly less than that from the clinic registry. There
      were no significant differences in the median age, number of months since the
      last Papanicolaou smear, incidence of abnormal Papanicolaou smear, education, or
      income of the subjects based on the recruitment strategy. CONCLUSION: A media
      based recruitment strategy was effective for this single-visit cervical
      prevention study. This approach may be effective for recruitment of other low
      income groups to clinical trials.

PMID- 11972384
TI  - Contribution of BRCA1 and BRCA2 to familial ovarian cancer: a gynecologic
      oncology group study.
AB  - OBJECTIVES: The aim of the study was to determine the prevalence of BRCA1 and
      BRCA2 germline mutations among ovarian cancer patients ascertained to have a
      family history of ovarian cancer. METHODS: Ovarian cancer patients were eligible
      if they had a family history of cancer that met any one of the following
      criteria: (1) a first-degree relative with ovarian cancer; (2) a second-degree
      relative with ovarian cancer plus a first-degree relative with breast cancer
      (diagnosed younger than 50 years of age); or (3) a first- and a second-degree
      relative with breast cancer (diagnosed younger than 50 years of age). The entire
      coding sequence of BRCA1 and exon 11 of BRCA2 were screened for germline
      alterations by single-strand conformation polymorphism analysis. RESULTS: Of 26
      eligible patients screened for mutations, 12 had deleterious alterations, 8 in
      BRCA1 and 4 in BRCA2. A correlation was noted between the presence of a BRCA1
      mutation and the strength of family history of breast ovarian cancer, with the
      likelihood of a mutation increasing with the number of affected relatives (P =
      0.0002). No association was detected between the location of mutations in BRCA1
      and the ratio of ovarian cancer cases relative to breast cancer (P = 0.28).
      CONCLUSIONS: Mutations in BRCA1 or BRCA2 are present in about 50% of ovarian
      cancer patients with at least one first-degree relative with disease, and in 70%
      of patients with two or more relatives with ovarian cancer.

PMID- 11972385
TI  - Enhancement of the adenoviral sensitivity of human ovarian cancer cells by
      transient expression of coxsackievirus and adenovirus receptor (CAR).
AB  - OBJECTIVE: The coxsackievirus and adenovirus receptor (CAR) is known to be a
      primary receptor for attachment during adenovirus infection of target cells and
      thus is closely related to adenoviral infection efficiency. To extend this notion
      to human ovarian cancer, we investigated the difference in expression levels of
      CAR in human ovarian cancer cell lines and whether their adenoviral sensitivities
      are enhanced by transient transfection of the CAR gene. METHODS: Adenoviral
      infection efficiency was examined by flow cytometry analysis, beta-galactosidase
      staining, and beta-galactosidase activity assay. Expression of the CAR-specific
      mRNA and protein was analyzed by reverse transcription polymerase chain reaction
      and flow cytometry, respectively. RESULTS: Expression of CAR in human ovarian
      cancer cell lines (SKOV3, 2774, PA-1, and OVCAR3) appeared to be correlated with
      their susceptibilities to adenovirus-mediated gene delivery. The 2774 and PA-1
      cells expressing an easily detectable level of CAR on the cell surface showed a
      higher susceptibility to infection with both AdCMVGFP and AdRSVbetagal than SKOV3
      and OVCAR3 cells, both of which had hardly detectable levels of CAR. Ectopic
      expression of the CAR gene by transient transfection of these ovarian cancer
      cells resulted in a dramatic increase in their adenoviral sensitivities.
      CONCLUSION: These data show that the expression of CAR is closely related to
      susceptibility to adenovirus infection in human ovarian cancer cells. These
      results indicate that the CAR gene can be a useful tool in boosting the
      efficiency of adenoviral vector-mediated gene therapy against human ovarian
      cancer.

PMID- 11972386
TI  - Effects of difluoromethylornithine on growth inhibition and apoptosis in human
      cervical epithelial and cancerous cell lines.
AB  - OBJECTIVE: Difluoromethylornithine(DFMO), an irreversible inhibitor of ornithine
      decarboxylase and an angiogenesis inhibitor, has been used in phase I cervical
      intraepithelial neoplasia (CIN) trials, producing a 50% regression of CIN 3
      lesions. DFMO is currently in phase II trials. In the experiments reported here,
      DFMO's growth inhibition and apoptosis induction were explored in an in vitro
      model to elucidate mechanisms of action. METHODS: Four immortalized cervical
      epithelial cell lines, serving as in vitro models of precancerous CIN lesions,
      and nine cervical carcinoma cell lines were studied. DFMO's growth inhibitory
      effect was tested in monolayer culture and in semisolid medium, and
      concentrations required for a 50% growth inhibition (IC(50)) with a 5-day
      treatment were determined. Apoptosis induction was analyzed using the terminal
      deoxynucleotidyl transferase assay of DNA fragmentation. RESULTS: DFMO inhibited
      growth of immortalized cervical epithelial cell lines and cervical cancer cell
      lines in monolayer culture and in semisolid medium. The immortalized cervical
      epithelial cell lines were more sensitive than the cervical cancer cell lines to
      DFMO's growth inhibitory effect. Concentrations required for 50% growth
      inhibition after a 5-day treatment ranged from 100 microM to >5 mM for cervical
      carcinoma cell lines and from 100 microM to 1 mM for immortalized cervical
      epithelial cell lines. DFMO induced apoptosis in precancerous and cancerous cell
      lines at a concentration of 5 mM, regardless of the cells' human papillomavirus
      status. CONCLUSION: DFMO inhibits the growth of cervical precancerous and
      cancerous cells in vitro in a dose-dependent and time-dependent manner, partially
      through inducing apoptosis.

PMID- 11972387
TI  - Glassy cell carcinoma of the cervix revisited.
AB  - OBJECTIVE: Glassy cell carcinoma (GCC) of the cervix has traditionally been
      characterized as an aggressive histologic subtype with poor outcomes. An earlier
      series from our institution supported a grim prognostic outlook, demonstrating a
      survival rate of only 55% in women with stage I disease. We present a comparison
      of a contemporary series of patients with GCC. METHODS: All cases of GCC treated
      from 1993 to 1999 identified by our tumor registry were reviewed for a variety of
      clinicopathologic features, treatment strategies, and outcome. RESULTS: A total
      of 403 cases of invasive cancer of the cervix were identified. There were 22
      patients with histologically confirmed GCC, representing only 5.4% of all
      cervical cancer diagnoses. Patients with GCC had an overall survival of 73%
      (16/22) and a disease-free survival of 64% (14/22). The incidence of stage I
      lesions was 64% (14/22). Overall survival of patients with stage I disease was
      86% (12/14), with a disease-free survival of 71% (10/14) at a median follow-up of
      28.5 months. Seven stage IB lesions were treated with surgery alone, whereas six
      received adjuvant radiation or chemoradiation following surgery. Two patients in
      each treatment group recurred, yielding an overall recurrence rate of 29% (4/14).
      However, of those who recurred with stage I disease, all 4 patients had two or
      more intermediate risk factors (lymph-vascular space invasion [LVSI], deep tumor
      invasion, or tumor size greater than 3 cm). CONCLUSIONS: Glassy cell carcinoma of
      the cervix appears to have a better prognosis than previously reported. We
      observed that intermediate risk histopathologic features identified in squamous
      cell cohorts are also predictive of a poorer outcome in patients with GCC. Thus,
      patients with LVSI, deep stromal invasion, and large tumor size are at the
      highest risk for pelvic relapse and should be candidates for adjuvant treatment.

PMID- 11972388
TI  - Phase II evaluation of 3-day topotecan with cyclophosphamide in the treatment of
      recurrent ovarian cancer.
AB  - OBJECTIVE: The aim of this trial was to investigate the toxicity and efficacy of
      a 3-day topotecan administration schedule in combination with cyclophosphamide in
      the management of recurrent ovarian cancer. METHODS: Patients with recurrent
      measurable ovarian cancer who had up to two prior chemotherapy regimens for the
      management of their disease participating in this phase II trial were to receive
      topotecan at a dose of 1.25 mg/m(2)/day x 3 days in combination with
      cyclophosphamide at 600 mg/m(2) on Day 1 every 21 days. Dose escalation and
      reductions were permitted. RESULTS: A total of 36 patients (median age = 65;
      range 37-84) were treated with this combination regimen. Seventeen were platinum
      sensitive and 19 were platinum-resistant. A total of 169 cycles of chemotherapy
      was administered (median = 4; range 1-10). Major toxicity included grade 4
      neutropenia (68.6%), neutropenic fever (7.1%), grade 3 thrombocytopenia (18.3%),
      and requirement for blood transfusion (19.5%). Dose escalation was possible in 3
      (8.3%), and dose reduction was required in 14 (38.9%) patients. Overall response
      rate was 25 and 44.5% stable disease. Median progression-free interval and
      overall survival was 5.4 and 23.5 months, respectively, independent of platinum
      sensitivity. CONCLUSION: The 3-day topotecan schedule in combination with
      cyclophosphamide appears to have good activity in recurrent ovarian cancer
      regardless of platinum sensitivity. Neutropenia was the only severe toxicity and
      was less prevalent than other reported trials of topotecan. This tolerable
      regimen offers patients more convenience and appears to have moderate activity.

PMID- 11972389
TI  - Functional outcomes and complications of continent urinary diversions in patients
      with gynecologic malignancies.
AB  - OBJECTIVE: The purpose of this study was to review our experience with continent
      urinary diversions in patients with gynecologic malignancies and evaluate the
      presentation and management of early and late complications. METHODS: A
      retrospective chart review was performed of all patients who underwent a
      continent urinary diversion on the Gynecologic Oncology Service at The University
      of Texas M. D. Anderson Cancer Center during the period January 1988 to March
      2001. We analyzed our data to evaluate potential risk factors for complications.
      Renal status, conduit integrity, and overall patient outcomes were also studied.
      RESULTS: We identified 40 patients who underwent a continent urinary diversion
      using an ileocolonic segment (Miami pouch technique). All patients had a history
      of gynecologic malignancies. The median age at the time of the procedure was 50
      years (range 24 to 76 years), and the median weight was 69.6 kg (range 47 to 125
      kg). A total of 39 patients (98%) had a history of radiotherapy. Continent
      urinary diversion was performed as part of an anterior pelvic exenteration in 12
      patients (30%), in conjunction with a total pelvic exenteration in 18 patients
      (45%), and as the main procedure in 10 patients (25%). The median estimated blood
      loss was 2100 ml (range 200 to 8500 ml). The median length of hospitalization was
      19.5 days (range 7 to 56 days). A total of 24 patients (60.0%) had a
      postoperative complications unrelated to the reservoir. Complications directly
      related to the continent urinary diversion were seen in 26 (65.0%) of 40
      patients. None of the patients in this study group developed chronic renal
      failure, and there were no perioperative deaths. At last evaluation, 36 (90%) of
      40 patients reported normal continent conduit function. CONCLUSIONS: Continent
      urinary diversion using an ileocolonic segment is a reasonable alternative to the
      ileal and transverse colon conduit in bladder reconstruction in patients
      undergoing radical pelvic surgery. The routine use of postoperative total
      parenteral nutrition, the chronic use of antibiotics after discharge from the
      hospital, and the routine use of imaging studies remain controversial. In this
      group of patients, the majority of complications may be successfully managed
      conservatively.

PMID- 11972390
TI  - Urinary tract dysfunction after radical hysterectomy for cervical cancer.
AB  - OBJECTIVES: To evaluate the urinary tract dysfunction following a radical
      hysterectomy and to compare the baseline urodynamical parameters of women who had
      uterine cervical carcinoma with women who had CIN 3. METHODS: A prospective case
      control study was conducted to evaluate preoperative and postoperative urinary
      tract function of thirty-two cervical carcinoma patients using twenty-seven CIN 3
      patients' preoperative urodynamical parameters as a baseline control. RESULTS:
      The rate of detrusor instability in women with preoperative cervical carcinoma
      was higher than that of women with CIN 3 (37.5 % vs. 14.8 %, P < 0.05). In the
      cervical carcinoma patients, there were 53.1 % who had normal urinary tract
      function, but after a radical hysterectomy they began voiding by abdominal
      straining. The impairment of bladder sensation, alteration of bladder capacity
      and bladder compliance, compromise of detrusor function, reduction of maximal
      urethral pressure and maximal urethral closure pressure, and the decrease of the
      pressure transmission ratio were significantly noted after a radical
      hysterectomy. The rate of genuine stress incontinence did not increase
      significantly (9.4 % vs. 18.8%, P > 0.05), but the rate of detrusor instability
      decreased significantly (37.5% vs. 15.6%, P < 0.05) after a radical hysterectomy.
      CONCLUSIONS: Changes of urinary tract function after a radical hysterectomy might
      be related to the partial sympathetic and parasympathetic denervation during a
      radical dissection. More than half of the women who preoperatively had normal
      urinary tract function needed to void by abdominal straining after radical
      surgery.

PMID- 11972391
TI  - Cellular glutathione content, in vitro chemoresponse, and the effect of BSO
      modulation in samples derived from patients with advanced ovarian cancer.
AB  - OBJECTIVES: The objective was to assess the relationship between glutathione
      content and drug sensitivity with glutathione modulation in ovarian cancer in a
      pilot study using 31 samples of freshly obtained ovarian tumor material from 26
      patients with advanced disease. METHODS: Processed tumor samples were screened to
      determine the glutathione content using an enzyme recycling assay modified for
      use in a 96-well plate format. Chemosensitivity testing (MTT assay) was used to
      assess sensitivity to cisplatin and doxorubicin and modulation using buthionine
      sulfoximine. Multidrug-resistance-associated protein MRP1 (putative drug
      glutathione conjugate transporter) expression was also assessed. RESULTS: There
      was a significant increase in the tumor cell GSH levels in samples from patients
      who had received previous chemotherapy (9) versus those from chemotherapy-naive
      patients (20), P = 0.005. In vitro chemosensitivity testing with doxorubicin and
      cisplatin (using LC(50) values, i.e., drug dose causing 50% reduction in cell
      survival relative to untreated control) failed to show a relationship with
      glutathione levels. Coincubation of cisplatin and doxorubicin with buthionine
      sulfoximine resulted in a significant increase in sensitivity to both of these
      drugs overall (cisplatin, P = 0.05; doxorubicin, P = 0.025), with 20 samples
      showing sensitization to a drug to which they were previously resistant. MRP1
      expression failed to show a correlation with drug sensitivity and glutathione
      levels. CONCLUSIONS: Our study supports the use of glutathione modulation using
      agents such as buthionine sulfoximine in patients with heavily pretreated, drug
      resistant ovarian cancer.

PMID- 11972392
TI  - Cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and Her-2/neu
      expression in ovarian cancer.
AB  - OBJECTIVES: Cyclooxygenase-2 (COX-2) seems to be involved in critical steps of
      cancer onset and progression. Abnormalities of epidermal growth factor receptor
      (EGFR) and Her-2/neu have been actively investigated in ovarian cancer and
      associated with unfavorable clinical outcome. The involvement of COX-2 in ErbB
      family pathways has been proposed. We investigated by immunohistochemistry the
      expression of COX-2, EGFR, and Her-2/neu in a series of advanced primary ovarian
      cancers. METHODS: The study included 76 consecutive stage IIIC-IV ovarian cancer
      patients with measurable disease after first surgery. Immunohistochemistry was
      performed on paraffin-embedded sections with rabbit antiserum against COX-2,
      murine monoclonal antibody (MoAb) 300G9 against Her-2/neu, and monoclonal
      antibody 108 against EGFR. RESULTS: No association among COX-2, EGFR, and HER
      2/neu was found. COX-2 positivity was found in a statistically significant higher
      percentage of unresponsive cases (80.0%) than in patients responding to
      chemotherapy (35.7%) (P = 0.0008). The association between COX-2 positivity and
      poor chance of response to treatment was retained in multivariate analysis. In
      the subgroup of patients who underwent explorative laparotomy COX-2-positive
      cases showed a shorter overall survival (P = 0.049). CONCLUSIONS: COX-2 could
      represent a possible new marker of sensitivity to platin-based chemotherapy in
      ovarian cancer. The lack of association of COX-2 with EGFR or Her-2/neu suggests
      that the ability of COX-2 to predict tumor sensitivity to chemotherapy is not
      dependent on EGFR or Her-2/neu status and could be independently associated with
      prognosis. In this context, the availability of agents able to specifically
      interfere with COX-2, Her-2/neu, or EGFR tyrosine kinase is of potential
      interest.

PMID- 11972393
TI  - Phase II evaluation of oral trimetrexate in mixed mesodermal tumors of the
      uterus: a gynecologic oncology group study.
AB  - OBJECTIVES: This is a Phase II group-wide study of the Gynecologic Oncology Group
      to determine the toxicity and objective response rate of trimetrexate (TMTX) in
      patients with advanced, persistent, or recurrent mixed mesodermal tumors of the
      uterus who have failed higher priority treatment protocols. METHODS: TMTX was
      administered orally at a dose of 5 mg/m(2) BID for 5 days and repeated in 14
      days. The maximum total dose was 50 mg/m(2)/week given every other week. The
      minimum treatment period was one course. Patients who had a complete response,
      partial response, or stable disease were continued on treatment for at least
      three courses. RESULTS: Twenty-eight patients were entered into the study. Three
      patients were ineligible based on review of pathologic materials. Twenty-five
      patients were evaluable for toxicity, and 21 were evaluable for response, as 4
      patients did not complete one course of therapy. Eleven patients had heterologous
      mixed mesodermal tumor (MMT) and 10 had homologous MMT. Of the 25 evaluable for
      toxicity, one patient had grade 4 platelet toxicity. No patient had grade 4
      neutropenia, while 4 patients had grade 3 decrease in absolute neutrophil count.
      One patient had grade 3 gastrointestinal toxicity, while 2 had grade 4 toxicity.
      There were no complete responses noted and only one partial response, for an
      overall response rate of 4.8%. The duration of the partial response was 15.2
      months. CONCLUSION: Oral TMTX has insignificant activity in the treatment of
      advanced, persistent, and recurrent uterine MMT at the dose and schedule
      administered.

PMID- 11972394
TI  - Persistent low-level "real" human chorionic gonadotropin: a clinical challenge
      and a therapeutic dilemma.
AB  - OBJECTIVE: The finding of persistent low-level human chorionic gonadotropin (hCG)
      with or without a preceding pregnancy event presents a rare but clinically
      important challenge and a therapeutic dilemma. These are patients with "real" hCG
      shown by the positive test in both serum and urine or by specialized testing. The
      problems associated with "phantom" hCG have been recognized and should now be
      clinically resolvable. Four cases of low-level "real" hCG are described to
      illustrate the problems encountered, the management, and the resolution achieved.
      METHODS: Two patients presented with persistent low-level hCG after hydatidiform
      mole pregnancy, one after an early pregnancy loss and one as amenorrhea and
      irregular bleeding. A detailed clinical description is provided to illustrate the
      difficulties encountered. RESULTS: All patients have real hCG. The hCG level of
      Patient 1 was responsive to hormonal contraception and disappeared with such
      medication. Over a period of 3 years hCG reappeared whenever estrogen was
      stopped. Patient 2 achieved two pregnancies and the hCG subsequently disappeared.
      The hCG in Patient 3 persisted over a period of 6 years although she is now
      menopausal. Patient 4 developed metastatic placental site trophoblastic tumor
      after 2 1/2 years of observation of low-level hCG. CONCLUSIONS: The finding of
      unexplainable low-level hCG in a patient without evidence of a uterine lesion or
      of trophoblastic metastases provides a therapeutic challenge. The administration
      of single-agent chemotherapy had no effect on the level of hCG in the three
      patients to whom it was administered. The administration of multiple-agent
      chemotherapy appears unjustified in the absence of a demonstrable trophoblastic
      tumor. A small number of trophoblastic cells must be providing this hCG and these
      cells may be quiescent for years. Nevertheless these cells may proliferate and
      manifest themselves as trophoblastic tumor. Continuing long-term surveillance of
      these patients is necessary.

PMID- 11972395
TI  - First-line chemotherapy with weekly paclitaxel and carboplatin for advanced
      ovarian cancer: a phase I study.
AB  - OBJECTIVES: Carboplatin and paclitaxel can be applied safely and effectively as
      single agents for the treatment of ovarian cancer on a weekly basis. A
      multicenter, phase-I study was conducted to investigate the maximum tolerated
      dose of a weekly combination regimen. METHODS: We enrolled 21 patients with
      primary, surgically resected, advanced ovarian cancer (FIGO III/ IV) and a median
      age of 59 (range, 35 to 79) years. For a fixed dose of paclitaxel at 100 mg/m(2),
      carboplatin was administered at levels equating an area under the curve of 2.0 (6
      patients), 2.5 (7 patients), and 3.0 (8 patients), respectively. Treatment
      schedule consisted of six cycles with drug delivery once a week, followed by a 2
      week break, and another six cycles. After a treatment-free interval of 28 days,
      three more cycles were administered. RESULTS: No dose-limiting toxicity was
      observed at the first level. Three patients developed dose-limiting toxicity
      (thrombocytopenia, neutropenic fever, and grade 3 neuropathy) receiving
      carboplatin at area under the curve 2.5. Another three patients developed dose
      limiting toxicity at the highest carboplatin dose, of whom two encountered
      refractory thrombocytopenia, whereas another experienced neutropenic fever
      despite prophylactic granulocyte-colony-stimulating factor use. Alopecia was
      documented in 17 patients. Neurotoxicity was usually mild to moderate. CA-125
      concentrations normalized (<35 U/ml) in 13 of 19 patients (68%) by the end of
      therapy. A 50% response was observed in 16 of 19 subjects. CONCLUSIONS: Weekly
      carboplatin and paclitaxel is a well-tolerated combination regimen in patients
      with primary, advanced ovarian cancer. The recommended dose for a phase II study
      is carboplatin at 100 mg/m(2) and carboplatin at area under the curve 2.0.

PMID- 11972396
TI  - Early invasive adenocarcinoma of the uterine cervix: criteria for nonradical
      surgical treatment.
AB  - OBJECTIVE: This retrospective study was undertaken to identify selection criteria
      for nonradical surgery for early invasive adenocarcinoma of the uterine cervix.
      METHODS: Seventy-nine patients with surgically treated cervical adenocarcinomas
      (with invasion to 5 mm or less) were examined clinicopathologically. The
      evaluation of stromal invasion was conducted according to the FIGO (1995) staging
      system. RESULTS: The mean age was 46 (range: 29-73) years, and the median follow
      up was 118 (9-348) months. Definitive treatment modalities included radical
      hysterectomy in 71 (89.9%) cases, modified radical hysterectomy in 2 (2.5%), and
      simple extrafascial hysterectomy without pelvic lymphadenectomy in 6 (7.6%).
      Postoperative adjuvant external radiation therapy was given to 5 (6.3%) patients.
      The histological subtypes were endocervical in 37 (46.8%) cases, endometrioid in
      32 (40.5%), and adenosquamous in 10 (12.7%). Forty-one (51.9%) patients had
      lesions with up to 3 mm of stromal invasion; of these, 24 (58.5%) had lesions
      with up to 7 mm of horizontal extension (stage IA1). Thirty-eight (48.1%)
      patients had lesions with stromal invasion greater than 3 mm and no greater than
      5 mm; of these, 4 had lesions with no wider than 7 mm of horizontal extension
      (stage IA2). Of 73 patients with pelvic lymphadenectomy, one (1.4%) tumor (depth:
      5 mm; width: 15 mm) had node metastases. Parametrial involvement was present in
      one (1.4%) patient (lesion depth: 5 mm; lesion width: 16 mm). None had adnexal
      metastasis. Eighty-eight percent of the patients with stromal invasion up to 3 mm
      had well-differentiated adenocarcinoma, compared to 53% of the patients with
      lesions invading more than 3 mm. Of all of the patients, 5 (6.3%) patients who
      received curative radical hysterectomies had recurrences and died. Among 5
      patients, one patient with central pelvic recurrence had a lesion invading to a
      depth of 3 mm and width of 7 mm, and the others had lesions with more than 3 mm
      of invasion and 15 to 36 mm of width. CONCLUSIONS: Patients with early invasive
      adenocarcinoma to a depth of 3 mm or less stromal invasion, including those who
      meet the criteria for FIGO stage IA1, may be treated with simple extrafascial
      hysterectomy without lymphadenectomy and oophorectomy.

PMID- 11972397
TI  - Evaluation of antibodies to human papillomavirus as prognostic markers in
      cervical cancer patients.
AB  - OBJECTIVES: We wished to evaluate whether the presence of antibodies to HPV or to
      the HPV oncoproteins E6 and E7 or type of HPV DNA is related to prognosis among
      cervical cancer patients. METHODS: Blood samples were drawn from 313 patients
      with incident, untreated cervical cancer on admission to two hospitals in Sweden.
      Patients were followed from enrollment in 1984-1991 until death or up to June
      1999. Clinical information was obtained from a review of medical records.
      Survival and cause of death were ascertained from both medical records and
      population-based cancer registries. The correlation of survival with antibodies
      to HPV16, to oncoproteins E6 and E7, and to type of HPV DNA was evaluated using
      multivariate Cox regression analysis, including stage, age, histology, and
      hospital in the model. RESULTS: Stage was the only significant prognostic factor
      influencing cervical cancer patient survival (OR = 3.62, 95% CI = 2.71-4.83). Age
      over 50 was associated with increased death rate among stage I-IIa patients (OR =
      2.29, 95% CI = 1.12-4.68). Presence of antibodies to the oncoproteins E6 and E7
      or to the HPV16 capsid or type of HPV DNA did not associate significantly with
      disease prognosis. CONCLUSIONS: Antibodies to HPV16 capsids and to oncoproteins
      E6 and E7 or type of HPV DNA do not appear to be useful as indicators of cervical
      cancer prognosis.

PMID- 11972398
TI  - Caspase 3-mediated focal adhesion kinase processing in human ovarian cancer
      cells: possible regulation by X-linked inhibitor of apoptosis protein.
AB  - OBJECTIVE: Cell adhesion is an important cell survival determinant and disruption
      of integrin-mediated signal transduction may be involved in anchorage-dependent
      cell death. We have examined the processing of focal adhesion kinase (FAK), a
      component of integrin-mediated signal transduction, in a cisplatin-sensitive
      human ovarian epithelial cancer cell line (OV2008), to test the possible role of
      FAK degradation in the control of apoptosis via regulation of cell attachment.
      METHODS: FAK processing after cisplatin treatment in the absence or presence of
      various caspase-inhibiting substances was analyzed by Western blot. Caspase
      inhibiting activities were introduced using cell-permeable peptides or adenoviral
      vector. RESULTS: Cisplatin-induced caspase 3 and FAK cleavage, cell detachment
      from the growth surface, and apoptosis in a temporally related and concentration
      dependent manner. FAK fragments were detected exclusively in cells detached from
      the culture surface. Addition of active caspase 3 to the whole cell lysate
      elicited a similar pattern of FAK cleavage. Pretreatment of whole cell lysates
      and cells with tetrapeptide inhibitors of caspases significantly decreased FAK
      cleavage induced by exogenous active caspase 3 and cisplatin, respectively.
      Overexpression of X-linked inhibitor of apoptosis protein (Xiap), an endogenous
      caspase inhibitor, attenuated the cisplatin-induced FAK processing, morphologic
      changes, and apoptosis. The inhibitory action of Xiap was abolished with the
      deletion of a functional motif required for caspase inhibition. CONCLUSION: These
      findings are consistent with our hypothesis that FAK processing is in part
      mediated by caspase 3, the activation of which is modulated by Xiap.

PMID- 11972399
TI  - The benefits of comprehensive surgical staging in the management of early-stage
      epithelial ovarian carcinoma.
AB  - OBJECTIVE: The management of understaged patients with apparent clinically early
      ovarian cancer is difficult. Options include offering chemotherapy based on
      histopathologic factors or reoperation to obtain the necessary information needed
      to assign an accurate surgical stage. This study aims to compare these two
      approaches and to define the role of staging surgery in this common patient
      population. METHODS: Retrospective chart reviews were carried out at the
      Universities of Manitoba and Saskatchewan over the period 1975 to 1999.
      Demographic data and surgical findings were abstracted and entered into a
      computerized database for analysis. Patients not having surgical staging
      procedures were offered platinum-based chemotherapy based on high tumor grades,
      dense adhesions, and presence of surface excrescences or large necrotic areas.
      Patients with surgically proven stage I disease were treated with no further
      therapy regardless of histopathologic factors. Descriptive statistics are used to
      summarize the data. Logistic and Cox regression models are used to identify
      significant predicting factors for recurrences and progression-free intervals.
      RESULTS: One hundred and thirty-eight patients presented with tumor
      macroscopically confined to the ovary at the time of laparotomy. The median age
      at presentation is 56.5 (18-90). The histology distribution was serous tumor in
      28.3%, mucinous in 26.1%, endometrioid in 23.2%, clear cell in 14.5%, anaplastic
      in 2.2%, and mixed types in 5.8%. The grade distribution was 47.1% grade 1, 27.5%
      Grade 2, and 25.4% Grade 3. Sixty-eight percent of the patients had a
      comprehensive surgical staging procedure initially. Thirty-six percent of these
      patients were found to have extraovarian metastases and were subsequently treated
      with adjuvant chemotherapy. Forty-three percent of those not having staging
      laparotomy were offered chemotherapy based on high risk factors only. At a median
      follow-up of 58 months. 77% of patients remained disease-free and 23% had
      recurrent disease. Of 60 patients with surgically proven stage I treated
      expectantly, 6 (10%) recurred, whereas of 25 unstaged patients treated
      expectantly due to lack of risk factors 7 (28%) recurred (P = 0.036). In patients
      treated expectantly, a significant survival advantage was noted in the staged
      group. Logistic regression showed age (OR 1.032, P = 0.043), high grade (OR 4.16,
      P = 0.003), and lack of a proper staging surgery (OR 2.62, P = 0.032) to be
      important factors predicting recurrence. In terms of progression-free interval,
      only age (OR 1.027, P = 0.048) and tumor grade (OR 3.62, P = 0.05) are
      significant predictors. CONCLUSION: Absence of surgical pathologic high-risk
      factors is inferior to comprehensive staging laparotomy findings in guiding
      recommendations for subsequent adjuvant therapy. Patients who have not been
      properly staged stand a significant risk of recurrent disease despite more
      frequent use of chemotherapy. All clinically early-stage ovarian cancer patients
      should be considered for comprehensive staging surgery prior to further treatment
      recommendations.

PMID- 11972401
TI  - Safety of paclitaxel in a patient with ovarian cancer and hyperbilirubinemia due
      to Rotor's syndrome.
AB  - BACKGROUND: Rotor's syndrome is a rare congenital disorder characterized by
      functional hyperbilirubinemia. Treatment decision may be challenging in a cancer
      patient with Rotor's syndrome, since the majority of the antineoplastic agents
      are metabolized in the liver and excreted via the biliary system. We report the
      first case of paclitaxel administration in a patient with ovarian cancer and
      elevated bilirubin levels due to Rotor's syndrome. CASE: A 50-year-old woman with
      Rotor's syndrome had an exploratory laparotomy and was diagnosed to have stage
      IIIC epithelial ovarian cancer. The baseline serum bilirubin value was 15.3
      mg/dL. She was started on a 50% dose of 87.5 mg/m(2) paclitaxel by 3-h infusion
      plus carboplatin AUC-6. The paclitaxel dose was increased by 25% at consecutive
      cycles until the standard dose of 175 mg/m(2)/3 h was achieved. Six cycles were
      administered without any metabolic derangement. The patient was rendered disease
      free with this treatment. CONCLUSION: Paclitaxel appears to be safe to administer
      to cancer patients with functional hyperbilirubinemia.

PMID- 11972400
TI  - Trends among gynecologic oncology inpatient deaths: is end-of-life care
      improving?
AB  - OBJECTIVE: The objective was to describe trends over time in key factors
      surrounding end-of-life care on a gynecologic oncology service at a tertiary
      cancer center. METHODS: Patients with gynecologic cancers who were hospitalized
      and died at our institution between 1992 and 1997 were identified using
      institutional databases. The study group consisted of 176 patients. For analysis,
      patients were divided into two groups: those who died between 1992 and 1994 and
      those who died between 1995 and 1997. Data were abstracted from medical records
      regarding the interval between placement of do-not-resuscitate (DNR) orders and
      death; the interval between the patient's being informed of her terminal-stage
      disease and death; the types of interventions performed near the end-of-life; and
      other factors related to end-of-life care. RESULTS: The average patient age on
      last admission to the hospital was 56 years, and the most common disease sites
      were ovary (47%), cervix (30%), and uterus (17%). Most deaths (82%) occurred on
      medical or surgical units, with the remainder occurring in the intensive care
      unit (12%) or emergency room (6%). The average interval between placement of DNR
      orders and death was longer among patients who died in 1995-1997 than among
      patients who died in 1992-1994 (49.6 days vs 19.2 days, P = 0.027). The average
      annual number of deaths (42.0 vs 16.7, P = 0.061) and the average length of
      hospital stay (13.3 vs 8.8 days; P = 0.079) decreased between 1992-1994 and 1995
      1997, but the differences did not reach statistical significance. Changes between
      patients who died in 1992-1994 and those who died in 1995-1997 in the interval
      between the last cycle of chemotherapy and death (87 days and 49 days,
      respectively; P = 0.29), the proportion of patients with a DNR order on admission
      (39 and 45%, respectively; P = 0.59), the proportion of patients admitted for
      terminal care only (22 and 19%, respectively; P = 0.47), and the proportion of
      patients who died awaiting transfer to hospice (32 and 22%, respectively; P =
      0.24) likewise did not reach statistical significance. CONCLUSIONS: Our data
      indicate that discussions about DNR orders are occurring earlier in relation to
      terminal events. However, we could not detect significant changes in the other
      outcome measures we studied. Major opportunities remain for further enhancements
      in the realm of advance planning for end-of-life care. Educational opportunities
      should be offered to physicians regarding communicating with patients about
      disease progression and end-of-life decision-making.

PMID- 11972402
TI  - Malignant peripheral nerve sheath tumor of the vulva: a multimodal treatment
      approach.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare in the
      gynecological population and have a high risk for local and distant failures.
      Multimodal management of a patient with MPNST of the vulva and review of the
      literature are outlined. CASE: A 34-year-old woman presented with a complaint of
      a rapidly increasing pelvic mass, pain, and difficulty ambulating. A disfiguring
      20 x 20-cm vulvar mass was identified and a recurrent MPNST diagnosed. Therapy
      included external-beam radiation, anterior pelvic exenteration with pelvic
      reconstruction, and adjuvant chemotherapy without complication. CONCLUSION: It is
      recommended that for malignant peripheral nerve sheath tumors of the vulva,
      complete surgical resection be performed with adjuvant radiation and chemotherapy
      in selected cases.

PMID- 11972403
TI  - Fallopian tube carcinoma presenting with a brain metastasis.
AB  - BACKGROUND: Fallopian tube carcinoma is a rare gynecologic cancer. An extensive
      literature search reveals no previous case report of fallopian tube carcinoma
      presenting with a brain metastasis. CASE: A 63-year-old woman presented with 3
      weeks of progressive left-sided weakness. CT scan of the brain revealed a
      solitary lesion in the right parietal lobe. The patient underwent a complete
      resection, followed by whole-brain radiation therapy. Pathologic review
      demonstrated adenocarcinoma with follicular structures. A directed workup
      revealed a large right adnexal mass. She underwent resection of a large fallopian
      tube carcinoma with normal ovaries. She recovered from surgery and is receiving
      combination chemotherapy. CONCLUSION: This is the first case report of a
      fallopian tube carcinoma presenting as a brain metastasis.

PMID- 11972404
TI  - Two cases of coincident carcinomas of the head and neck and the uterine cervix.
AB  - BACKGROUND: Human papillomavirus (HPV) is an independent risk factor for select
      head and neck carcinomas and most uterine cervix carcinomas. We report two
      patients with synchronous diagnoses of cervical cancer and HPV-related head and
      neck cancer. CASE: One patient was a 53-year-old woman with regionally metastatic
      tonsillar carcinoma treated surgically and with adjuvant radiation. Abnormal
      vaginal bleeding developed. Gynecologic examination showed advanced cervical
      carcinoma. The other patient was a 78-year-old woman surgically treated for
      carcinoma of the left anterior nose. Five months later, symptoms of recurrent
      nasal carcinoma and concurrent vaginal bleeding developed. Gynecologic
      examination showed advanced cervical carcinoma. CONCLUSIONS: These cases of
      coincident tumors demonstrate possible systemic susceptibility to the
      carcinogenic effects of HPV. The common association of HPV with both uterine
      cervix cancers and select head and neck cancers should prompt early evaluation of
      gynecologic or upper aerodigestive tract symptoms for patients with known HPV
      related cancers.

PMID- 11972405
TI  - Salvage hemipelvis radiotherapy with fertility preservation in an adolescent with
      recurrent vulvar carcinoma.
AB  - BACKGROUND: To preserve fertility, hemi-pelvis irradiation was chosen for
      locoregional groin recurrence of vulvar cancer in an adolescent. CASE: A case of
      squamous cell vulvar carcinoma in uncommonly young patient is presented. First
      surgical management (local excision of T1N0M0 tumor of the right labia minora)
      was performed at the age of 16.5 years. Further therapy included wide local
      resection of recurrent local lesion, two subsequent ipsilateral groin dissections
      of nodal metastases (with extranodal spread at the first instance), and
      ipsilateral pelvic lymphadenectomy. The patient was administered external beam
      irradiation of 45 Gy to the hemi-pelvis followed by 10.8 Gy boost to the right
      inguinal region. After 6.5 years from the completion of radiotherapy the patient
      is free of disease. She managed to conceive but the labor was premature and the
      infant died in its 7th week of life. CONCLUSION: In this case salvage hemi-pelvic
      irradiation for groin metastases of vulvar cancer has proved to be an effective
      treatment, allowing preservation of hormonal and obstetric functions. Partial
      post-irradiation damage of the uterus might have caused premature labor. Thus,
      special obstetric care is advisable in such situations.

PMID- 11972406
TI  - Primary invasive vaginal cancer in the setting of the Mayer-Rokitansky-Kuster
      Hauser syndrome.
AB  - BACKGROUND: The Mayer-Rokitansky-Kuster-Hauser syndrome occurs in 1 in 4000 to
      5000 female births. Primary vaginal cancer constitutes less than 2% of all
      malignancies of the female genital tract. A report of the first case of the
      unlikely occurrence of both of these developments in the same patient is
      presented. CASE: A 34-year-old nulligravid Philippine woman with a history of
      Mayer-Rokitansky-Kuster-Hauser syndrome presented with a 5-month history of
      bleeding from a blind vaginal pouch. Vaginal biopsy identified a moderately
      differentiated endometrioid adenocarcinoma. Exploratory laparotomy, bilateral
      salpingo-oophorectomy, pelvic and iliac lymph node samplings, and excision of a
      mullerian remnant were performed with no evidence of disease. A FIGO Stage I
      vaginal cancer was assigned and pelvic irradiation was given. Disease recurred 4
      months later and the patient underwent total pelvic exenteration. More than 1
      year since the exenteration procedure, she is without evidence of disease.
      CONCLUSION: This is the first reported case of a primary vaginal cancer in a
      patient with Mayer-Rokitansky-Kuster-Hauser syndrome. It is a reminder that
      routine gynecologic examinations are still warranted as these patients are at
      risk for malignant changes in residual mullerian tissues.

PMID- 11972408
TI  - The use of PET scanning in ovarian cancer.

PMID- 11972407
TI  - The effect of raloxifene on the incidence of ovarian cancer in postmenopausal
      women.
AB  - OBJECTIVE: The aim of this study was to determine the incidence of ovarian cancer
      in postmenopausal women treated with raloxifene compared with placebo. METHODS:
      This analysis comprises integrated data from seven randomized, placebo-controlled
      trials of raloxifene (N = 9837). Ovarian cancer cases were identified from the
      safety database and reviewed by a gynecologic adjudication review board. RESULTS:
      Sixteen cases of ovarian cancer were reported: 8 women (79.4/100,000 patient
      years) on placebo and 8 (37.4/100,000 patient-years) on pooled raloxifene doses.
      The relative risk of ovarian cancer associated with raloxifene therapy was 0.50
      (95% confidence interval, 0.19-1.35). CONCLUSION: Raloxifene use was not
      associated with an increased risk for ovarian cancer.

PMID- 11972410
TI  - MMR vaccine: review of benefits and risks.

PMID- 11972411
TI  - Keeping pace with the elusive Bordetella pertussis.

PMID- 11972412
TI  - A new era of research into Bordetella pertussis pathogenesis.

PMID- 11972413
TI  - Myositis in children with meningococcal disease: a role for tumour necrosis
      factor-alpha and interleukin-8?
AB  - OBJECTIVES: Myalgia is under-recognized in meningococcal disease (MCD). In septic
      shock, myositis is thought to be mediated by pro-inflammatory cytokines such as
      tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and interleukin-6
      (IL-6) but this has never previously been studied in MCD. We aimed to demonstrate
      whether muscle damage mediated via TNF-alpha and other pro-inflammatory cytokines
      occurs in MCD, as estimated by creatine kinase skeletal muscle isoenzyme (CK-MM)
      and cardiac isoenzyme (CK-MB) concentrations. METHODS: A total of 68 children,
      median age 2.7 years, with a diagnosis of MCD were prospectively studied.
      Severity of disease was measured using the Glasgow Meningococcal Septicaemia
      Prognostic Score (GMSPS). Severe disease was defined as a GMSPS of > or =8. TNF
      alpha, IL-8, IL-6 and IL-1Ra concentrations were determined on samples taken on
      admission. RESULTS: CK-MM correlated significantly with TNF-alpha, IL-8 and
      GMSPS. There was no significant correlation between CK-MB and TNF-alpha or IL-6,
      but CK-MB correlated with GMSPS and IL-8. Fifty-six percent of children with MCD
      had evidence of muscle damage as manifested by elevated CK-MM. CONCLUSIONS: TNF
      alpha and IL-8 may be potential mediators in the pathophysiology of skeletal
      muscle damage in MCD.

PMID- 11972414
TI  - Pattern of meningitis in Al-Ain medical district, United Arab Emirates--a decadal
      experience (1990-99).
AB  - OBJECTIVES: Haemophilus influenzae vaccine was introduced in the United Arab
      Emirates in 1999. Our objective was to describe the pattern of meningitis in a
      health district in the decade before the introduction of the vaccine and compare
      it with the data from elsewhere. METHODS: For this retrospective study we
      included 128 meningitis cases reported from 1990 to 1999. Information on the
      cases was abstracted from the case notification forms and clinical and laboratory
      data from the hospital case notes. RESULTS: H. influenzae was the most common
      cause of bacterial meningitis (n=59, 46.1%) followed by Streptococcus pneumoniae
      (n=20, 15.6%). Meningitis was a disease primarily of infants and children and the
      median age was 15 months. One fifth of the patients (n=27) had neurological
      sequelae of which 33.3% had seizures and 25.9% developed deafness. 18.9% (10 out
      of 53) of H. influenzae isolates were resistant to ampicillin compared with 5.9%
      (3 out of 51) to chloramphenicol. 78.9% (15 out of 19) of S. pneumoniae isolates
      were susceptible to penicillin. CONCLUSIONS: The epidemiology of meningitis in
      our health district is similar to the epidemiology of meningitis during the pre
      vaccine era in other countries.

PMID- 11972415
TI  - Epidemiology of Norwalk-like human caliciviruses in hospital outbreaks of acute
      gastroenteritis in the Stockholm area in 1996.
AB  - OBJECTIVES: Outbreaks of acute gastroenteritis associated with 'Norwalk-like
      viruses' (NLVs) cause significant health problems in hospitals. Hospital
      outbreaks in the Stockholm area in 1996 were investigated, in order to identify
      the magnitude of the problem, the mode of transmission, the effect of control
      measures and the genetic variability of outbreak strains. Determining the
      epidemiological and clinical significance involves a broad range of
      possibilities. METHODS: Ten hospitals, representing 66% of the hospitals in the
      Stockholm area, participated in the study, which included 211 wards. Of these, 18
      were selected as control. A standardized protocol that included personal contacts
      was administered. Outbreak wards were visited between 5 and 10 times. Wards that
      had reported outbreaks in 1996 were prospectively followed through 1999 by
      personal contacts, and the available data from 1991 on outbreak reports were
      collected. A total of 253 stool samples from outbreaks in 1996 were analyzed by
      electron microscopy (EM) for the presence of NLVs. Positive samples were
      confirmed by the reverse transcriptase-polymerase chain reaction (RT-PCR).
      RESULTS: In total, 4 326 patients and 1 119 staff were exposed on the 43 wards
      that reported 54 outbreaks. The mean attack rate was 13% for patients and 21% for
      staff. The number of outbreaks in 1996 outnumbered the reported outbreaks in the
      preceding years (4-70%) and later years (35-40%). Admission to 24 (56%) of the
      outbreak wards was stopped. The mean duration of illness for patients was 35
      hours and for staff, 30 hours. The main symptoms were diarrhoea (80%) and
      vomiting (68%). Genotyping revealed that the majority of the hospital outbreaks
      in the Stockholm area in 1996 were caused by a single NLV strain. CONCLUSIONS:
      The study confirmed that outbreaks of NLV are an increasing public-health problem
      in hospitals. The risk of being affected by an outbreak was significantly greater
      on wards that had reported outbreaks in the previous year. It was not obvious
      which measures had helped to shorten the outbreaks to any appreciable extent.
      Different managements must therefore be carefully interpreted and adapted to the
      prevailing circumstances. Genotyping of strains is an important tool of getting a
      better insight into transmission routes and the mechanism behind the appearance
      of epidemic strains.

PMID- 11972416
TI  - Does race protect an oriental population from developing lipodystrophy in HIV
      infected individuals on HAART?
AB  - OBJECTIVES: Lipodystrophy, hyperlipidaemia and hyperinsulinaemia are common
      metabolic complications of highly active antiretroviral therapy (HAART) in human
      immunodeficiency virus (HIV)-infected Caucasians. We questioned whether such
      complications also occur in other races. METHODS: A cross-sectional analysis was
      performed in an outpatient clinic of a university teaching hospital with 156
      Koreans, divided into HIV-infected subjects receiving HAART (n=57, group 1),
      HAART-naive subjects (n=42, group 2), and healthy controls (n=57, group 3).
      Lipodystrophy was assessed by physical examination and questionnaire and body
      composition by dual-energy X-ray absorptiometry. Fasting triglyceride, total
      cholesterol, low-density (LDL) and high-density lipoprotein (HDL) cholesterol,
      free fatty acid (FFA), Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB),
      glucose, insulin, c-peptide, leptin, cortisol, dehydroepiandrosterone (DHEA),
      CD4, CD8 lymphocyte counts and HIV RNA load were measured. RESULTS: Lipodystrophy
      was observed in only 3.5% of HAART-treated HIV-infected Koreans. No statistical
      difference in regional fat accumulation or peripheral fat wasting was observed
      between groups 1, 2 and 3. No statistical difference in triglyceride, total
      cholesterol, LDL cholesterol, FFA, ApoA1, ApoB, glucose, insulin, C-peptide,
      leptin, cortisol, and DHEA were observed between groups 1, 2 and 3. HDL
      cholesterol was significantly lower in HIV-infected individuals compared to
      controls. CONCLUSIONS: Lipodystrophy, hyperlipidaemia, and insulin resistance are
      rare metabolic complications of HAART in an oriental HIV-infected group of
      individuals. These findings warrant further race-specific metabolic complication
      studies in HIV-infected subjects receiving HAART.

PMID- 11972417
TI  - Genotyping of Enterocytozoon bieneusi in AIDS patients from the north west of
      England.
AB  - OBJECTIVES: In this study Enterocytozoon bieneusi -positive faeces samples from
      AIDS patients in the north west of England were investigated by polymerase chain
      reaction (PCR) and DNA sequencing for potential zoonotic origins. METHODS: The
      ITS and flanking regions of the rDNA was amplified by PCR and product sequenced.
      Sequences were compared with those held on GenBank to ascribe known genotypes.
      RESULTS: Of 13 E. bieneusi -positive samples tested, all gave a 508 bp
      amplification product by PCR. The samples yielded the following: genotypes B
      (n=11; so far only been found in humans), D (n=1; has been reported from humans
      and a laboratory macaque) and K (n=1; previously identified only from a cat).
      CONCLUSIONS: A possible zoonotic link with cats has been demonstrated for one
      human case. The origin of the majority of cases in the north west of England is
      unknown and may indicate that genotype B is solely a human pathogen.

PMID- 11972418
TI  - Acupuncture-associated arthritis in a joint with an orthopaedic implant.
AB  - Viral infection is a well-recognized complication of acupuncture therapy.
      Bacterial infection however is rare. We report a rare case of intra-articular
      bacterial knee infection due to inadvertent acupuncture needle penetration.

PMID- 11972419
TI  - Chronic relapsing salmonella osteomyelitis in an immunocompetent patient: case
      report and literature review.
AB  - We present the first case of Salmonella virchow causing a relapsing bone
      infection at the same site 12 years apart in an otherwise healthy patient.
      Chronic relapsing osteomyelitis caused by a zoonotic salmonella may become
      increasingly important in view of the increased incidence of zoonotic salmonella
      infections. Based on this case, we recommend 3 months of therapy with a quinolone
      when treating a chronic relapsing zoonotic salmonella osteomyelitis.

PMID- 11972420
TI  - Recurrent Guillain-Barre syndrome as a complication of immune reconstitution in
      HIV.

PMID- 11972421
TI  - Pseudomonas pericarditis in an immunocompetent newborn: unusual presentation with
      review of the literature.
AB  - Acute purulent pericarditis is a rare entity in the neonatal age group. The most
      common isolated organisms are Staphylococcus aureus, Haemophilus influenzae, and
      Streptococcus pneumoniae. Other organisms, like Pseudomonas aeruginosa, have been
      seldom implicated with only one case of Pseudomonas pericarditis reported in the
      neonatal period. The prognosis is often considered very poor in this age group.
      This article describes Pseudomonas pericarditis in a 1-week-old immunocompetent
      female newborn who was successfully managed with combined medical and surgical
      therapy.

PMID- 11972422
TI  - Citrobacter mediastinitis following cardiac surgery in a neonate.

PMID- 11972423
TI  - Stenotrophomonas maltophilia bacteraemia in two patients with cystic fibrosis
      associated with totally implantable venous access devices.

PMID- 11972424
TI  - Echovirus 30 meningitis: a new cause for cerebral venous thrombosis?

PMID- 11972426
TI  - Isolation of a serogroup 29E meningococcal strain carrying Group-C siaD capsular
      gene.

PMID- 11972425
TI  - Cytomegalovirus retinitis during immunotherapy for common variable
      immunodeficiency.

PMID- 11972427
TI  - A multidrug, including voriconazole, resistant oral Candida infection in an AIDS
      patient effectively treated with echinocandin.

PMID- 11972429
TI  - Glucocorticoid therapy in the fetus and newborn--Introduction.

PMID- 11972430
TI  - Antenatal glucocorticoids and growth: single versus multiple doses in animal and
      human studies.
AB  - In recent years, many clinicians have prescribed repeated courses of
      glucocorticoids to pregnant women at risk of early preterm birth. The published
      literature has provided reassurance from randomized controlled trials that single
      course treatment improves postnatal lung function without deleterious
      consequences, but we do not yet have data from randomized trials designed
      specifically to investigate the effects of repeated courses. Data from animal
      studies have, for many years, provided evidence that prenatal exposure to
      glucocorticoids restricts fetal growth and, more recently, has suggested a role
      in programming the individual to adult disease. Multivariate analyses from non
      randomized cohorts have also suggested associations between repeated treatments
      and reduced birth weight, but we await results from randomized controlled trials
      currently in progress to provide more definitive answers. Regardless of any
      effect on growth, the possibility that adult health and disease may be programmed
      by fetal exposure to glucocorticoids will ensure our need to balance the ability
      of these agents to improve newborn survival with the potential consequences in
      later life.

PMID- 11972431
TI  - Perinatal glucocorticoid therapy and neurodevelopmental outcome: an epidemiologic
      perspective.
AB  - A relatively brief course of antenatal glucocorticoids (ACS), given to reduce the
      severity of respiratory distress syndrome in preterm infants, improves survival
      and appears to protect against brain damage. In clinical trials as well as
      observational studies, ACS have been associated with a decreased risk of
      intraventricular haemorrhage and cerebral palsy. In observational studies a
      decreased risk of white-matter damage, identified with cranial ultrasound, has
      been observed. There is some evidence, from observational studies, that repeated
      courses of ACS (typically given at weekly intervals) can reduce the rate of fetal
      head growth, and experiments in animals provide further support for this
      possibility. In contrast to the effects of a brief course of ACS, postnatal
      glucocorticoids (PCS), given to preterm infants to reduce the severity of chronic
      lung disease have been associated with an increased risk of neurologic
      impairment. Available evidence suggests that PCS does not improve survival.
      Further study is needed of the neurodevelopmental consequences of both multiple
      courses of ACS, as well as PCS.

PMID- 11972432
TI  - Antenatal glucocorticoids and the developing brain: mechanisms of action.
AB  - Glucocorticoids are critical for normal brain development. There is no doubt that
      prenatal treatment with synthetic glucocorticoid affords great benefit to the
      preterm infant. However, animal studies, now carried out in many species,
      indicate that there may be some long-term physiological costs of early exposure
      to excess glucocorticoid, and that these appear sex-dependent. Further, the
      effects may not become apparent until later life. Given the dynamics of
      corticosteroid receptor systems in late gestation, it is likely that there are
      critical windows of development when specific regions of the brain are more
      sensitive to the influence of synthetic glucocorticoid. Once such windows have
      been identified it will be possible to target prenatal treatments, so as to
      maximize benefit and reduce risk of long-term effects. Notwithstanding, the data
      reviewed below indicate that caution should be exercised in the use of multiple
      course glucocorticoid therapy during pregnancy.

PMID- 11972433
TI  - Glucocorticoid programming of pituitary-adrenal function: mechanisms and
      physiological consequences.
AB  - Increasing epidemiological evidence supports the notion that adverse events in
      fetal life permanently alter the structure and physiology of the adult offspring,
      a phenomenon dubbed 'fetal programming'. In particular, low weight or thinness at
      birth in humans is associated with an increased risk of cardiovascular and
      metabolic disorders as well as neuroendocrine dysfunction in adult life.
      Glucocorticoid administration during pregnancy is well-documented to both reduce
      offspring birth weight and alter the maturation of organs (hence their use to
      accelerate fetal lung maturation in premature labour). Here data are reviewed
      which show, in rodents and other models, that antenatal exposure to endogenous or
      exogenous glucocorticoids reduces offspring birth weight and produces permanent
      hypertension, hyperglycaemia, hyperinsulinaemia, altered behaviour and
      neuroendocrine responses throughout the lifespan. Processes underlying fetal
      programming include determination of the 'set point' of the hypothalamic
      pituitary-adrenal (HPA) axis and of tissue glucocorticoid receptor (GR)
      expression. Similar HPA axis hyperreactivity occurs in lower birth weight humans
      and may be an early manifestation of the 'low birth weight' phenotype.

PMID- 11972434
TI  - Glucocorticoids, inflammation and the perinatal lung.
AB  - Many women delivering preterm infants at less than 30 weeks gestation have
      subclinical chorioamnionitis. Based on current guidelines, maternal
      glucocorticoid treatment is given to induce lung maturation. Fetal exposure to
      proinflammation can cause acute and chronic injury, but inflammation also can
      induce fetal lung maturation. Both antenatal glucocorticoids and inflammation
      modulate lung development, by inducing the surfactant system, inducing structural
      maturation, and inhibiting alveolarization. The opportunities for the future are
      to develop new safer strategies to mature the preterm foetus, and the risks are
      potential adverse interactions of repetitive glucocorticoid exposures and
      unrecognized fetal exposure to inflammation.

PMID- 11972435
TI  - Postnatal glucocorticoid therapy for prevention of bronchopulmonary dysplasia:
      routes of administration compared.
AB  - Postnatal systemic and inhaled glucocorticoid therapies continue to be used in
      the management of bronchopulmonary dysplasia (BPD). Systemic dexamethasone
      therapy has been studied longer than aerosolized glucocorticoid therapy. Several
      prophylactic trials of systemic dexamethasone therapy demonstrated a reduction in
      the incidence of BPD and neonatal mortality. However, evidence of potentially
      serious acute and long-term adverse effects has reduced enthusiasm for use of
      systemic dexamethasone therapy. Although no trial to date of inhaled
      glucocorticoid therapy showed a reduction in the incidence of BPD, some studies
      demonstrated secondary pulmonary benefits with few short-term adverse effects.
      This article compares the clinical efficacy and safety of these two routes of
      administration of glucocorticoid therapy.

PMID- 11972436
TI  - Antenatal glucocorticoids and renal function after birth.
AB  - Antenatal glucocorticoid treatment is widely used in cases of threatening preterm
      delivery. Both human and animal studies have confirmed that glucocorticoids
      promote pulmonary maturation in fetuses. Several studies indicate that prenatal
      glucocorticoids also stimulate renal maturation. Although the current knowledge
      about the effects of glucocorticoids on kidney function is mainly concentrated on
      short-term effects, there are animal studies suggesting that antenatal
      glucocorticoid treatment may also cause permanent changes in kidney morphology
      and renal function. It still remains to be investigated if antenatal
      glucocorticoid treatment induces long-term effects in humans.

PMID- 11972437
TI  - Prenatal dexamethasone treatment of fetuses at risk for congenital adrenal
      hyperplasia: benefits and concerns.
AB  - Virilization due to congenital adrenal hyperplasia (CAH) can effectively be
      prevented or diminished by prenatal dexamethasone given to the mother. This
      treatment, which should only be considered in families with a previous child with
      a virilizing form of the disease, has to start already at 6-7 weeks of gestation.
      Thus, the treatment has to be given 'blindly' to all mothers at risk until the
      diagnosis of an affected female can be ascertained by analysis of DNA from a
      chorionic villous biopsy, which cannot be performed until the 10th week. Since
      CAH is inherited as an autosomal recessive disease and only affected girls
      benefit from the treatment, seven out of eight fetuses are treated unnecessarily.
      This makes it especially important to monitor possible side effects. Adverse
      effects on brain and kidneys have been shown in animals exposed to large doses of
      dexamethasone during the second trimester. Too few follow-up human studies are
      reported to date to allow definite conclusions on possible side effects in man.
      Therefore, treatment should be done within controlled clinical studies.

PMID- 11972438
TI  - Classification and prediction in pharmacogenetics--context, construction and
      validation.

PMID- 11972439
TI  - Pharmacogenomics and personalised medicine. SMI Conference on Pharmacogenomics
      and Personalised Medicine, 26-28 September, 2001, The Hatton, London, UK.

PMID- 11972440
TI  - Beta-adrenergic receptor polymorphisms and drug responses in asthma.
AB  - Genetic variation in the beta 2-adrenoceptor and its associated proteins is
      common and therefore potentially relevant to the clinician. Several functional
      SNPs have been described but in vitro studies have yielded inconsistent results.
      Confounding due to the variable presence of other polymorphic alleles may be the
      explanation and the recent definition of ADRB2 haplotypes offers the opportunity
      for clarification. In vitro studies have concentrated on downregulation and
      desensitization as functional end points. However, the relevance of these
      phenomena is unclear and extrapolating in vitro data to the clinical setting may
      not be appropriate. To date, only the Arg(16) polymorphism appears to be
      important in determining beta 2-agonist drug responses but the data as well as
      their application are limited. The results of prospective studies based on
      selection by ADRB2 haplotype will be necessary before a more general application
      of this knowledge can be encouraged.

PMID- 11972441
TI  - The role of pharmacogenetically-variable cytochrome P450 enzymes in drug abuse
      and dependence.
AB  - The risk of drug dependence is determined by the interaction of drug, individual
      and environment. 'Pharmacogenetics' is the study of the influence of heredity on
      the response to drugs and their fate in the body; these studies aim to improve
      the understanding of inter-individual variability in drug response. The authors
      have applied this research approach to the study of drug metabolism and
      dependence. Specifically the interaction of genetically variable hepatic
      cytochrome P450 (CYP) enzymes and their effect on self-administration of drugs
      has been examined. Many drugs of abuse are substrates (e.g., amphetamines,
      codeine, nicotine) or inhibitors (e.g., (-)-cocaine) of polymorphic CYPs. Drug
      metabolism by genetically polymorphic enzymes can have significant clinical
      implications relating to drug toxicity, therapeutic failure, drug-drug
      interactions, disease susceptibility and abuse liability. There is good evidence
      that drug metabolism by genetically variable CYPs can influence the risk of drug
      dependence, the amount of drug consumed by dependent individuals and some of the
      toxicities associated with drug-taking behavior. It is anticipated that
      pharmacogenetics will be used to identify individuals at a greater risk for
      specific drug dependencies, provide information that can lead to novel treatment
      and prevention approaches as well as provide guidance for individualization of
      treatment choice.

PMID- 11972442
TI  - Cytochrome P450 polymorphisms and response to antipsychotic therapy.
AB  - Antipsychotic drugs are used for the treatment of schizophrenia and other related
      psychotic disorders. The antipsychotics currently available include older or
      classical compounds and newer or atypical agents. Most antipsychotic drugs are
      highly lipophilic compounds and undergo extensive metabolism by cytochrome P450
      (CYP) enzymes in order to be excreted. There is a wide interindividual
      variability in the biotransformation of antipsychotic drugs, resulting in
      pronounced differences in steady-state plasma concentrations and, possibly, in
      therapeutic and toxic effects, during treatment with fixed doses. Many classical
      and some newer antipsychotics are metabolized to a significant extent by the
      polymorphic CYP2D6, which shows large interindividual variation in activity.
      Other CYPs, especially CYP1A2 and CYP3A4, also contribute to the interindividual
      variability in the kinetics of antipsychotics and occurrence of drug
      interactions. No relationship between CYP2D6 genotype or activity and therapeutic
      effects of classical antipsychotic drugs has been found in the few studies
      performed. On the other hand, some investigations suggest that poor metabolizers
      (PMs) of CYP2D6 would be more prone to over-sedation and, possibly, Parkinsonism
      during treatment with classical antipsychotics, while other studies, mostly
      retrospective, have been negative or inconclusive. For the newer antipsychotics,
      such data are lacking. To date, CYP2D6 phenotyping and genotyping appear,
      therefore, to be clinically useful for dose predicting only in special cases and
      for a limited number of antipsychotics, while their usefulness in predicting
      clinical effects must be further explored.

PMID- 11972443
TI  - Opioid receptor polymorphisms and opioid abuse.
AB  - The sequencing of the human genome is only the first step. The next step is to
      determine the function of these genes and in particular, how alterations in
      specific genes lead to major human disorders. Many laboratories are now focusing
      on identifying and characterizing single nucleotide polymorphisms (SNPs), to
      determine which correlate in frequency with certain population groups who may be
      particularly susceptible to certain diseases. The mu opioid receptor (MOR), which
      mediates the clinically important analgesic effects of drugs like morphine as
      well as the euphoria sought by heroin abusers, exhibits several dozen
      polymorphisms. Several of these are associated with altered receptor function and
      individuals at risk for drug abuse.

PMID- 11972444
TI  - CYP2D6 allele frequency in European Caucasians, Asians, Africans and their
      descendants.
AB  - Over 40 cytochrome P450 (CYP) 2D6 allelic variants have been discovered thus far.
      The alleles may be classified on the basis of the level of activity for which
      they encode CYP2D6 enzymes, into functional, non-functional and reduced function
      groups. CYP2D6 allele frequency is known to vary amongst racial/ethnic groups.
      Generally, for European Caucasians and their descendants, the functional group of
      alleles are predominant, with a frequency of 71%. Non-functional alleles
      represent 26% of the variability, mainly CYP2D6*4. In Asians and their close
      descendants, functional alleles represent only ~ 50% of the frequency of CYP2D6
      alleles. Asians and Pacific Islanders have a high frequency (median = 41%) of a
      reduced function allele, CYP2D6*10, contributing to the population shift to the
      right of metabolic rates indicating slower metabolism. Information concerning
      Amerindians from North (Canada), Central and South America indicate comparatively
      low frequencies of CYP2D6*10, perhaps a "founders" effect. The frequency of
      functional alleles in Africans and African Americans is also about 50%. Both
      Africans and African Americans have reduced function alleles representing 35% of
      allele variation, mainly CYP2D6*17. African Americans, however, have more than
      twice the median frequency of nonfunctional alleles compared with Africans (14.5%
      vs 6.3%). Non-functional and reduced function alleles represent about 50% of
      allele frequency in Black populations but a much greater variety than carried in
      Asians. Since alleles which encode for no or reduced functioning clearly affect
      metabolic activity of drugs mediated by CYP2D6, studies are needed in populations
      in which these alleles play a major role in order to assure optimal dosing
      recommendations are based on empirical pharmacogenetics.

PMID- 11972446
TI  - The application of genetics to the discovery of better medicines.
AB  - The availability of the human genome sequence and the increasing knowledge of
      functional polymorphisms will highlight new therapeutic approaches to treat
      diseases with unmet medical need and will allow the targeting of new and existing
      therapies to those patients who will derive the most benefit without the risk of
      serious side effects. This review describes how genetic information can be used
      to improve the drug discovery and development process. It should be emphasized,
      however, that although it is anticipated that high-throughput genetic studies
      will provide novel biological insights into disease, it is not a replacement for
      careful hypothesis-driven experiments. Rather, it is essential to combine genetic
      studies with carefully conducted preclinical and clinical experiments to extract
      the true value of high-throughput genetics-based research.

PMID- 11972445
TI  - Comparative genome analysis and pathway reconstruction.
AB  - Pathway reconstruction builds on genome and biochemical data with the aim of
      reconstructing higher level interactions between identified enzymes in a specific
      genome, in particular the different enzyme pathways (species or
      individual/patient). Metabolite flow in a pathway is analyzed by different tools,
      such as elementary mode analysis. This reveals key enzymes and pharmacological
      targets in the enzyme network. An overview of bioinformatic tools and algorithms
      for these tasks, application examples and recent results from these techniques
      are presented. Target selection, drug development and optimization can all be
      sped up using these approaches.

PMID- 11972447
TI  - Online genomics facilities in the new millennium.
AB  - The review begins by providing a brief typology of biological databases on the
      Internet, illustrated by examples of the most influential resources of each kind.
      We then take an insider look at one typical on-line genomic resource -- the yeast
      genome database hosted at the Munich Information Center for Protein Sequences
      (MIPS) -- and explain how and why it has evolved from a basic sequence repository
      to a multidomain knowledge base. The role of community efforts in curating and
      annotating genome data is discussed. The crucial role of data integration and
      interoperability in developing next-generation genomic facilities is underscored.

PMID- 11972448
TI  - Genaissance pharmaceuticals, inc.
AB  - Genaissance Pharmaceuticals, Inc. (Nasdaq: GNSC) is the world leader in the
      discovery and use of gene variation for the development of personalized
      medicines. In addition, the company has established partnerships with some of the
      world's top biopharmaceutical companies. The company has initiated the
      development of its own pipeline of products -- HAP Clozapine for schizophrenia
      and HAP Statin for cholesterol management -- utilizing its proprietary genetic
      markers. The company also markets its technology and clinical development skills
      to the pharmaceutical industry as a complete solution for improving the
      development, marketing and prescribing of drugs.

PMID- 11972450
TI  - Alteration in the cytosolic triacylglycerol biosynthetic machinery leads to
      decreased cell growth and triacylglycerol synthesis in oleaginous yeast.
AB  - Altered nutrient content (levels of glucose) caused a drastic reduction in cell
      growth and triacylglycerol (TAG) production in the wild-type (WT) Rhodotorula
      glutinis. This was due to the decreased level of synthesis of TAG biosynthetic
      enzymes, reflected by a reduction in enzyme activity. A similar observation was
      made in the case of non-lethal mutants of TAG-deficient oleaginous yeast, namely
      TAG1 and TAG2, which were generated by ethyl methane sulphonate mutagenesis.
      Metabolic labelling of TAG-deficient cells with [(14)C]acetate,
      [(32)P]orthophosphate and [(14)C]mevalonate showed a negligible TAG formation
      with minimal alterations in phospholipid and sterol compositions. Assays on the
      activities of cytosolic TAG biosynthetic enzymes revealed that lysophosphatidic
      acid and diacylglycerol acyltransferases (ATs) were defective in TAG1 and TAG2
      respectively. The activity of membrane-bound isoforms of TAG biosynthetic enzymes
      remains unaltered in the mutants. Analysis of cytosolic TAG biosynthetic enzymes
      by immunoblotting and immunoprecipitation indicated that the defective ATs were a
      part of the TAG biosynthetic multienzyme complex. Quantitatively, the cytosolic
      lysophosphatidic acid-AT was comparable between TAG1 and the WT. However,
      diacylglycerol-AT was relatively less in TAG2 than the WT. These results
      demonstrated that either by decreasing the nutrient content or mutating the
      enzymes of the soluble TAG biosynthetic pathway, TAG production was decreased
      with concomitant reduction in the cell growth.

PMID- 11972449
TI  - Antizyme induction by polyamine analogues as a factor of cell growth inhibition.
AB  - The polyamines spermidine and spermine and their diamine precursor putrescine are
      essential for mammalian cell growth and viability, and strategies are sought for
      reducing polyamine levels in order to inhibit cancer growth. Several structural
      analogues of the polyamines have been found to decrease natural polyamine levels
      and inhibit cell growth, probably by stimulating normal feedback mechanisms. In
      the present study, a large selection of spermine analogues has been tested for
      their effectiveness in inducing the production of antizyme, a key protein in
      feedback inhibition of putrescine synthesis and cellular polyamine uptake.
      Bisethylnorspermine, bisethylhomospermine, 1,19-bis-(ethylamino)-5,10,15
      triazanonadecane, longer oligoamine constructs and many conformationally
      constrained analogues of these compounds were found to stimulate antizyme
      synthesis to different levels in rat liver HTC cells, with some producing far
      more antizyme than the natural polyamine spermine. Uptake of the tested compounds
      was found to be dependent on, and limited by, the polyamine transport system, for
      which all these have approximately equal affinity. These analogues differed in
      their ability to inhibit HTC cell growth during 3 days of exposure, and this
      ability correlated with their antizyme-inducing potential. This is the first
      direct evidence that antizyme is induced by several polyamine analogues.
      Selection of analogues with this potential may be an effective strategy for
      maximizing polyamine deprivation and growth inhibition.

PMID- 11972451
TI  - The high-affinity calcium[bond]calmodulin-binding site does not play a role in
      the modulation of type 1 inositol 1,4,5-trisphosphate receptor function by
      calcium and calmodulin.
AB  - Modulation of the inositol 1,4,5-trisphosphate (InsP(3)) receptors (InsP(3)R) by
      cytosolic calcium (Ca(2+)) plays an essential role in Ca(2+) signalling, but
      structural determinants and mechanisms responsible for the InsP(3)R regulation by
      Ca(2+) are poorly understood. In the present study, we expressed rat InsP(3)R
      type 1 (InsP(3)R1) in Spodoptera frugiperda cells using a baculovirus-expression
      system and reconstituted the recombinant InsP(3)R1 into planar lipid bilayers for
      functional analysis. We observed only minor effects of 0.5 mM of calmodulin (CaM)
      antagonist W-7 on the Ca(2+) dependence of InsP(3)R1. Based on a previous
      analysis of mouse InsP(3)R1 [Yamada, Miyawaki, Saito, Nakajima, Yamamoto-Hino,
      Ryo, Furuichi and Mikoshiba (1995) Biochem J. 308, 83-88], we generated the
      Trp(1577)-->Ala (W1577A) mutant of rat InsP(3)R1 which lacks the high-affinity
      Ca(2+)[bond]CaM-binding site. We found that the W1577A mutant displayed a bell
      shaped Ca(2+) dependence similar to the wild-type InsP(3)R1 in planar lipid
      bilayers. Activation of B cell receptors resulted in identical Ca(2+) signals in
      intact DT40 cells lacking the endogenous InsP(3)R and transfected with the wild
      type InsP(3)R1 or the W1577A mutant cDNA subcloned into a mammalian expression
      vector. In the planar lipid bilayer experiments, we showed that both wild-type
      InsP(3)R1 and W1577A mutant were equally sensitive to inhibition by exogenous
      CaM. From these results, we concluded that the interaction of CaM with the high
      affinity Ca(2+)[bond]CaM-binding site in the coupling domain of the InsP(3)R1
      does not play a direct role in biphasic modulation of InsP(3)R1 by cytosolic
      Ca(2+) or in InsP(3)R1 inhibition by CaM.

PMID- 11972454
TI  - MR follow-up of small experimental intracranial haemorrhages from hyperacute to
      subacute phase.
AB  - PURPOSE: To compare pulse sequences in revealing intracranial bleeding from the
      hyperacute to subacute phase. MATERIAL AND METHODS: We injected 0.3-1 ml of
      autologous blood into the brain of 8 rabbits. MR imaging was performed
      immediately after haematoma creation and then at determined intervals up to 9-12
      days. All images were analysed by two observers. After the last MR investigation,
      the brain was fixed in formalin. The last MR images were compared to the fixed
      brain sections and to the histologic findings. RESULTS: T2*-weighted GE
      sequences, both conventional spoiled and echoplanar sequences, revealed the
      intraparenchymal haematomas as hypointensities in all but 1 case, which was
      negative from the second day onward (a rabbit with 0.3 ml blood injected). The
      signal patterns remained unchanged during the follow-up. The haematoma sizes and
      shapes corresponded well to gross pathology. Blood in the cerebrospinal fluid
      (CSF) space was detected with T2*-weighted GE sequences in a great majority of
      the examinations during the first 2 days. The cases with the smallest injected
      volume of blood were negative. SE sequences were rather insensitive. The FLAIR
      sequence often revealed blood in CSF spaces but not in the brain. CONCLUSION: T2*
      weighted GE sequences are capable of revealing very small intraparenchymal
      haemorrhages from the hyperacute to the subacute phase, and blood in CSF spaces
      during at least the first 2 days.

PMID- 11972452
TI  - Expression and purification of functional recombinant meningococcal transferrin
      binding protein A.
AB  - Pathogenic bacteria of the genus Neisseria have a siderophore-independent iron
      uptake system reliant on a direct interaction between the bacterial cell and
      human transferrin (hTf), a serum protein. In the meningococcus, this uptake
      system is dependent on two surface-exposed, transferrin-binding proteins (Tbps),
      TbpA and TbpB. TbpA is highly conserved among meningococcal strains, and is
      thought to be a porin-like integral protein that functions as a gated channel for
      the passage of iron into the periplasm. TbpB is more variable in size, lipidated
      and fully surface-exposed. Given its location on the cell surface, its role in
      pathogenicity and interstrain sequence conservation, TbpA is currently being
      regarded for inclusion in a meningococcal vaccine effective against all
      serogroups. This requires gaining knowledge of the ligand-receptor interactions.
      In the present study we have optimized a procedure for obtaining purified,
      functionally active recombinant TbpA at a level and stability necessary for the
      initiation of such studies.

PMID- 11972455
TI  - MR angiography in the follow-up of coiled cerebral aneurysms after treatment with
      Guglielmi detachable coils.
AB  - PURPOSE: Intra-arterial digital subtraction angiography (DSA) has been considered
      the gold standard examination in the follow-up of patients treated with Guglielmi
      detachable coils (GDCs). However, DSA is an invasive and expensive investigation
      and results in exposure to ionising radiation to both patient and operator. The
      aim of this study was to compare MR angiography (MRA) with DSA with regard to
      patency of the occlusion of aneurysms following GDC treatment. MATERIAL AND
      METHODS: We performed 75 MRA and DSA examinations on 51 patients treated with
      GDCs. The examinations were performed 3-36 months after embolisation and the
      interval between MRA and DSA was less than 1 week. Hard copies of both studies
      were interpreted retrospectively and independently for residual flow within the
      aneurysm, residual aneurysmal neck, and parent and branch vessel flow. RESULTS:
      Patency status of parent and branch vessel flow was correctly identified with MRA
      in all patients except 1. The sensitivity of MRA in revealing residual flow
      within the aneurysm was 97%. The specificity in ruling out residual flow within
      the aneurysm was 91%. CONCLUSION: MRA may replace DSA in the long-term follow-up
      of coiled cerebral aneurysms. The initial follow-up examination should, however,
      include both modalities.

PMID- 11972456
TI  - Embolization of cranial/spinal tumours and vascular malformations with hydrogel
      microspheres. An experience of 69 cases.
AB  - OBJECTIVE: To evaluate polymethyl methacrylate hydrogel microspheres (HMs) as an
      embolization material in the management of hypervascular craniofacial and spinal
      lesions. MATERIAL AND METHODS: Sixty-nine patients with vascular lesions of the
      craniofacial and spinal regions underwent embolization with HM. The pathologies
      included craniofacial tumours (n=38), cranial arteriovenous malformations (AVMs)
      (n=7), dural AVM (n=1), cavernous carotid fistula (n=1), spinal tumours (n=7),
      spinal AVMs (n=6), orbital lesions (n=4) and scalp AVMs (n=5). Surgery was done
      in 56 patients. The blood loss at surgery, tumour shrinkage, surgical cleavage
      and ease of removal of tumour was noted from the records. Histopathology was
      available in 39 patients. A follow-up of 3 months to 6 years was available in 13
      patients in whom embolization was the sole treatment. Surgical and
      histopathological findings were correlated with angio-embolization findings.
      RESULTS: HMs were easy to inject through the microcatheter with good control.
      Good devascularization was obtained in 61 patients and partial in 8 patients. Two
      patients developed complications due to presence of anastomoses between intra-
      and extracranial circulation and 1 patient due to tumor swelling. Histopathology
      showed presence of HMs in all the lesions, with minimal inflammatory reaction in
      2 patients. Patients with spinal lesions treated with embolization only
      stabilised in neurologic deficits. CONCLUSION: HMs are highly suitable as
      embolization agents in the management of craniofacial and spinal hypervascular
      lesions.

PMID- 11972457
TI  - CT characterization of inflammatory paranasal sinus disease in cystic fibrosis.
AB  - PURPOSE: In patients with cystic fibrosis (CF) the prevalence of paranasal sinus
      affection approaches 100%. We hypothesized that the hyperviscous mucus reducing
      mucociliary clearance in CF patients could give sinonasal inflammatory patterns
      different from those in non-CF patients. We wanted to compare the extent and
      distribution of paranasal sinus disease and the inflammatory patterns in these
      two groups of patients. MATERIAL AND METHODS: One-hundred-and-eight CF patients
      (3-54 years old) and 79 controls (7-51 years old) with paranasal sinus disease
      confirmed at coronal CT were compared. The extent of disease was noted for each
      sinus and summed for all sinuses. Inflammatory patterns were identified and
      classified into: 1) routine surgery group (sporadic, infundibular and ostiomeatal
      complex (OMC) patterns) and 2) complex surgery group (sinonasal polyposis and
      sphenoethmoid recess (SER) patterns). RESULTS: CF patients had more widespread
      sinonasal inflammatory changes and more advanced disease for each sinus. Most CF
      patients displayed sinonasal polyposis and SER patterns while most controls
      displayed sporadic, infundibular or OMC patterns. As a result, 67% of CF patients
      were classified to the complex surgery group, compared to only 19% of controls.
      CONCLUSION: The impaired mucociliary clearance in CF causes widespread
      inflammatory paranasal sinus disease, with inflammatory patterns more often
      requiring extensive surgery, with a higher risk of cerebrospinal fluid leak or
      bleeding, or involving areas that are more difficult to reach with the endoscope.

PMID- 11972458
TI  - Utility of the tumor bed marker in patients with breast cancer receiving
      induction chemotherapy.
AB  - PURPOSE: Induction or neoadjuvant chemotherapy is used in patients with locally
      advanced breast cancer to offer a higher rate of conservative surgery. The
      possibility of reduction in size, even in some cases complete clinical and
      mammographic regression, can make the localization of the tumor bed difficult at
      the time of surgery. The purpose of this study was to describe our experience
      about the utility of US-guided implantation of a metallic marker in patients with
      breast cancer before induction chemotherapy. MATERIAL AND METHODS: Forty-three
      patients with 44 masses were diagnosed with percutaneous biopsy of breast
      carcinoma. Before beginning of the induction chemotherapy all of them were
      referred for metallic marker placement. A metallic harpoon was placed under US
      guidance. RESULTS: One patient died during the chemotherapy. Six underwent
      mastectomy, and 9 still had a palpable tumor at the time of surgery. In the
      remaining 27 patients (with 28 lesions) pre-operative wire localization of the
      tumor bed was carried out: in 11 cases the harpoon was necessary for the
      localization of the tumor bed, in 6 the harpoon was useful, and in 11 patients
      the localization of the tumor could have been done without the marker. No
      complications were observed and the marker remained stable in all patients.
      CONCLUSION: In patients who undergo induction chemotherapy, the placement of a
      metallic harpoon under US guidance is a safe, simple and inexpensive technique
      for localization of the tumor bed previous to conservative surgery.

PMID- 11972459
TI  - Differentiation of phyllodes tumors versus fibroadenomas.
AB  - PURPOSE: To determine if mammographic and sonographic findings allow
      discrimination between phyllodes tumor and large sized fibroadenoma, which mimic
      each other in the clinical, radiologic and histopathologic appearances. MATERIAL
      AND METHODS: Thirty-one histopathologically proven masses including 12 phyllodes
      tumors and 19 fibroadenomas 3 cm or greater in diameter were compared. In total
      28 women were retrospectively evaluated by mammography and pre-operative
      sonography. RESULTS: Mammography revealed a high-density mass compared with
      surrounding fibroglandular breast tissue to be present in 9 of the 12 (75%)
      phyllodes tumors and 7 of the 19 (37%) fibroadenomas. At sonography a mass, which
      had a round or lobulated shape, marked posterior acoustic enhancement and
      intramural cystic areas, were statistically significantly more likely to be
      phyllodes tumors than fibroadenomas. None of the other mammographic or
      sonographic characteristics proved to be useful in differentiating phyllodes
      tumors and fibroadenomas. CONCLUSION: Although masses of high density at
      mammography, circumscribed border associated with posterior acoustic enhancement
      and internal cystic areas at sonography should suggest the diagnosis of phyllodes
      tumors rather than large sized fibroadenomas, there was a substantial overlap in
      the mammographic and sonographic characteristics of these two tumors. Therefore,
      an excisional biopsy would be necessary for equivocal masses.

PMID- 11972460
TI  - Airway changes in children with mucopolysaccharidoses.
AB  - OBJECTIVE: To assess the CT findings of the airway in children with
      mucopolysaccharidoses (MPS). MATERIAL AND METHODS: The study included 13 patients
      (9 boys, 4 girls; age range 2-17 years; mean age 9.2 years) with MPS: 6 with
      Hunter syndrome, 3 with Maroteaux-Lamy syndrome, 2 with Sanfilippo syndrome, 1
      with Hurler/Scheie syndrome and 1 with Morquio syndrome. CT of the airways was
      done in the axial section with 3-mm collimation from the oropharynx at the level
      of C3 to the base of the lung. The shape of the vocal cords and trachea at the
      level of T1 was evaluated. The tracheal surface area (TSA) at the level of T1 was
      measured both in patients and in age-matched subjects. RESULTS: CT showed an
      abnormality of the vocal cords in 7 of the 13 patients. Six patients had an
      abnormal shape and 7 had an inhomogenous density. The abnormalities included
      elliptical (5 of 6) and star-shaped (1 of 6) cords. Eight of 13 tracheas were
      also abnormal, either U-shaped (6 of 8) or worm-shaped (2 of 8). The TSA was
      significantly smaller in patients (79.6+/-28.9 mm2) than in control subjects
      (138.1+/-50.1 mm2). The TSA of those < or =9 years was 61.4+/-15.2 mm2 as
      compared with 99.9+/-23.5 mm2 for the control group. The TSA of patients > or =11
      years was 107.1+/-25.3 mm2 as compared with 187.6+/-32.0 mm2 for the control
      group. CONCLUSION: Significant changes in the shape of the vocal cords and
      trachea in patients with MPS were found. The most common abnormal configuration
      of trachea was the U-shape. The TSA was smaller in patients with MPS than in
      controls. The airway changes may be due to abnormal submucosal storage of
      substances such as keratan or dermatan sulfate.

PMID- 11972461
TI  - Correlation of immunologic status with high-resolution CT and distributions of
      pulmonary tuberculosis.
AB  - PURPOSE: To investigate the correlation of cluster of differentiation (CD)4
      lymphocyte counts with high-resolution CT (HRCT) findings and distribution of
      pulmonary tuberculosis. MATERIAL AND METHODS: Thirty-seven bacteriologically
      proven pulmonary tuberculosis, clinically non-AIDS, patients underwent HRCT and
      CD4 lymphocyte counts in peripheral blood cells were obtained within 3 days after
      the CT examinations. Patients were categorized into four groups according to CD4
      lymphocyte counts (A >800; B 800-500; C 500-200; D <200). HRCT findings analyzed
      were as follows: typical, atypical, and mixed findings of post-primary
      tuberculosis, common, uncommon, and mixed distribution, and number of lobes
      involved. RESULTS: CD4 lymphocyte counts correlated with the degree of the
      mixture of atypical CT findings (rho=0.565, p<0.001) and the degree of the
      mixture of uncommon distribution (rho=0.431, p<0.01). Number of involved lobes
      showed no statistically significant correlation (rho=0.209, p=0.21). CONCLUSION:
      In patients with low CD4 levels, atypical HRCT findings co-exist with typical
      findings, and uncommon sites are involved in addition to common sites.

PMID- 11972462
TI  - Visual grading of emphysema severity in candidates for lung volume reduction
      surgery. Comparison between HRCT, spiral CT and "density-masked" images.
AB  - PURPOSE: To investigate which of three types of CT imaging yielded the best
      results in estimating the degree of emphysema in patients undergoing evaluation
      for lung volume reduction surgery (LVRS), whether there was any difference in
      this regard between the cranial and caudal part of the lung, and whether the
      degree of emphysema had an impact on the estimation. MATERIAL AND METHODS: Four
      radiologists visually classified different degrees of emphysema on three
      different types of CT images into four groups. The degree of emphysema was
      calculated by a computer. The three types of images were as follows: HRCT images
      (2-mm slice thickness); spiral CT images (10-mm slice thickness); and density
      masked images (spiral CT images printed with pixels below -960 HU, depicted in
      white). RESULTS: The conventionally presented images from HRCT and spiral CT
      yielded the same results (60% respective 62% correct classifications) in
      assessing the degree of emphysema irrespective of localisation. Significantly
      improved results were obtained when the spiral CT images were presented as
      density-masked images (74%). CONCLUSION: There was no difference between HRCT and
      spiral CT in assessing the degree of emphysema in candidates for LVRS.
      Improvement can be achieved by the use of density-masked images.

PMID- 11972463
TI  - Reproducibility of scoring emphysema by HRCT.
AB  - PURPOSE: We evaluated the reproducibility of three visual scoring methods of
      emphysema and compared these methods with pulmonary function tests (VC, DLCO,
      FEV1 and FEV%) among farmer's lung patients and farmers. MATERIAL AND METHODS:
      Three radiologists examined high-resolution CT images of farmer's lung patients
      and their matched controls (n=70) for chronic interstitial lung diseases.
      Intraobserver reproducibility and interobserver variability were assessed for
      three methods: severity, Sanders' (extent) and Sakai. Pulmonary function tests as
      spirometry and diffusing capacity were measured. RESULTS: Intraobserver kappa
      values for all three methods were good (0.51-0.74). Interobserver kappa varied
      from 0.35 to 0.72. The Sanders' and the severity methods correlated strongly with
      pulmonary function tests, especially DLCO and FEV1. CONCLUSION: The Sanders'
      method proved to be reliable in evaluating emphysema, in terms of good
      consistency of interpretation and good correlation with pulmonary function tests.

PMID- 11972464
TI  - Emphysema in heavy smokers with normal chest radiography. Detection and
      quantification by HCRT.
AB  - PURPOSE: To determine the severity and extent of emphysema in heavy smokers by
      high-resolution CT (HRCT) and to correlate the findings with spirometric tests
      (STs) and symptomatology. MATERIAL AND METHODS: Fifty adult smokers with a mean
      age of 53 years with a smoking history of more than 30 pack years and normal
      chest radiographs underwent HRCT of the chest and ST (FEV1, FEV1/FVC, PEFR).
      Among these, 22 had symptoms of pulmonary disease and 28 were asymptomatic.
      Quantification of emphysema was done using a density mask program and the visual
      scoring method. The results were correlated with ST and symptomatology. RESULTS:
      58% (29 out of 50) of the subjects had significant emphysema on HRCT. Eleven out
      of 15 with normal ST showed emphysema on HRCT while 2 with airflow obstruction on
      ST showed normal CT scores. 14% (4 out of 28) asymptomatic subjects had severe
      emphysema compared to 64% of symptomatic subjects. Emphysematous changes were
      predominantly seen in upper lung zones in 48% of the patients while in 52% it was
      distributed equally in both upper and lower zones. The number of pack years of
      smoking showed a positive correlation with CT scores. The correlation between
      HRCT scores and ST was statistically significant. CONCLUSION: A significant
      number of asymptomatic and clinically undiagnosed smokers tend to have
      significant emphysema. HRCT helps in early detection of disease and thus helps
      implementation of preventive measures.

PMID- 11972465
TI  - Depiction of vasculature in small hepatocellular carcinoma, and dysplastic
      nodules evaluated with carbon dioxide ultrasonography and angiography.
AB  - PURPOSE: To evaluate the vascularity in dysplastic nodules and well
      differentiated and moderately to poorly differentiated hepatocellular carcinomas
      (HCCs) less than 2 cm using carbon-dioxide (CO2) US and angiography. MATERIAL AND
      METHODS: A total of 115 pathologically proven small liver tumors (0.7
      approximately 2.0 cm) were included in the study. There were 31 dysplastic
      nodules, 49 well-differentiated HCCs and 35 moderately to poorly differentiated
      HCCs. A comparative study of angiography and CO2 US was carried out. RESULTS: Of
      the dysplastic nodules, 28 out of 31 tumors were hypo- or isovascular at CO2 US.
      Twenty-seven out of 31 tumors were hypovascular at angiography. Of the well
      differentiated HCCs, 38/49 showed hypervascularity at CO2 US while 24/49 tumors
      were hypervascular at angiography. All moderately to poorly differentiated HCCs
      showed hypervascularity at CO2 US, compared to 30/35 tumors at angiography.
      CONCLUSION: Most of the dysplastic nodules were hypovascular and most of the
      moderately to poorly differentiated HCCs were hypervascular. The vascularity of
      well-differentiated HCCs was in between the above tumors. Both CO2 US and
      angiography were equally effective in demonstrating the vascularities in
      dysplastic nodules and moderately to poorly differentiated HCCs. CO2 US was
      significantly superior to angiography when identifying the vascularity in well
      differentiated HCCs.

PMID- 11972466
TI  - Accuracy of CT in local staging of gallbladder carcinoma.
AB  - PURPOSE: To evaluate the accuracy of CT for staging gallbladder cancers,
      especially the T-factor of the TNM staging system. MATERIAL AND METHODS: CT
      investigations of 100 patients with surgically proven gallbladder cancers were
      retrospectively analyzed. Dynamic helical CT was performed in 16 patients and
      conventional CT in the remaining 84. On CT, three radiologists attempted tumor
      staging for these patients; the majority opinion was used for final decision.
      According to CT protocols (dynamic helical CT vs. conventional CT) and each tumor
      type (thickened wall/intraluminal mass/massive), the accuracy of CT staging was
      compared. The CT staging was correlated with the surgico-pathologic results.
      RESULTS: The overall accuracy of CT for staging gallbladder cancers was 71%; it
      was 79% for T1 and T2 tumors, 46% for T3 tumors, and 73% for T4 tumors. For all
      three readers, the poorest accuracy was obtained in T3 tumors. No statistically
      significant difference was noted in the accuracy between the groups undergoing
      conventional CT and dynamic helical CT. A statistically significant difference
      was noted in the accuracy for staging thickened wall and intraluminal mass types
      of tumors (p<0.05); the highest accuracy was obtained in the intraluminal mass
      type (89%) and the massive type (83%), while it was 54% in the thickened wall
      type. CONCLUSION: The accuracy of tumor staging with CT in patients with
      gallbladder cancer depends on the morphological type of tumor. The poorest result
      is obtained in the thickened wall type.

PMID- 11972467
TI  - Interobserver agreement in ultrasound examination of the biliary tract.
AB  - PURPOSE: To prospectively evaluate the interobserver agreement in US examination
      of the gallbladder and the biliary tract performed by an experienced and a novice
      radiologist. MATERIAL AND METHODS: Fifty consecutive patients underwent US
      examination because of clinically suspected gallstones. The examination was
      performed by a consultant and a trainee radiologist on the same day. The
      following outcome measures were registered: presence of gallstones, filling of
      the gallbladder, thickness of the gallbladder wall, splitting of the gallbladder
      wall, fluid around the gallbladder, diameter of the common bile duct (CBD), and
      presence of CBD stones. RESULTS: None of the radiologists observed CBD stones or
      fluid around the gallbladder. The CBD was clearly distinguished by both observers
      in all patients. There was good agreement in the conclusions of the two
      radiologists regarding the presence of gallbladder stones and substantial
      agreement regarding the filling of the gallbladder and splitting of the
      gallbladder wall. Significant difference existed in the measurements by the two
      radiologists regarding the thickness of the gallbladder wall and the diameter of
      the CBD. CONCLUSION: The novice radiologist's expertise in the primary diagnosis
      of uncomplicated gallstone disease was as good as the one provided by the
      experienced colleague. The significant interobserver difference in the
      measurements of the thickness of the gallbladder wall and the CBD diameter might
      indicate that assessment of these parameters requires extensive practise and the
      opinion of an experienced colleague must be sought in cases where complications
      are suspected.

PMID- 11972468
TI  - MR and ultrasound in screening of patients with suspected biliary tract disease.
AB  - PURPOSE: The diagnostic value and cost-efficiency of MR imaging were compared
      with US before endoscopic retrograde cholangiopancreatography (ERCP) in patients
      with clinically suspected biliary tract disease. MATERIAL AND METHODS: In a
      prospective study of 219 patients, 85 were examined with both MR and US before
      ERCP. RESULTS: To find the correct diagnosis in the jaundiced patients the
      sensitivity of US, MR and ERCP was 53%, 93%, and 89%, respectively. In the
      patients with abdominal upper quadrant pain and normal serum bilirubin, the
      sensitivity of US, MR and ERCP was 50%, 100% and 70%, respectively. Examination
      with MR costs four times more than US. Screening with US and supplemental MR in
      non-diagnostic cases would cost 80% of the total amount compared to screening
      with MR only. CONCLUSION: MR had a higher sensitivity than US for diagnosing
      biliary tract disease and MR was superior to US in visualising stones in the
      common bile duct and in diagnosing the cause of cholestasis. However, screening
      with US and supplemental MR in non-diagnostic cases is at present most cost
      effective. With increased accessibility and slightly lower costs, MR will
      probably replace US as screening method in patients with suspected biliary tract
      disease.

PMID- 11972469
TI  - Bowel wall visualisation at CT colonography.
AB  - PURPOSE: To evaluate the quality of bowel wall visualisation at CT colonography
      and the impact of examination in the supine and prone positions. MATERIAL AND
      METHODS: After bowel preparation, 111 patients underwent CT colonography. Air
      distension, degree of fluid redistribution with change in body position (supine
      and prone), influence of residual stool on bowel wall assessability, and quality
      of overall colon visualisation were evaluated using scales. RESULTS: Thirty of
      110 patients (27%) had complete overall visualisation of the colon wall and 52
      (47%) had subtotal visualisation of a limited part of the colon. The entire colon
      was more often air-filled in the prone position (46%) than in the supine position
      (18%). Joint review of supine and prone data showed that for all colon segments,
      except the sigmoid (86%), > or =95% of the patients had complete air filling. All
      patients had residual fluid. In 75% to 99%, depending on segment, fluid did not
      interfere with the bowel wall visualisation in the combined evaluation of supine
      and prone data sets. Thirty-one patients had residual stool with potential
      negative influence on polyp detection. CONCLUSIONS: The colon wall was
      completely, or almost completely, visualised in 75% of the patients, and
      examination in the supine and prone positions was necessary for complete
      visualisation.

PMID- 11972470
TI  - MR imaging of the neural foramina of the cervical spine. Comparison of 3D-DESS
      and 3D-FISP sequences.
AB  - PURPOSE: To assess whether a single three-dimensional double-echo steady state
      (3D-DESS) sequence can produce equivalent results when compared to a 3D free
      induction with steady precession (3D-FISP) sequence for the evaluation of the
      neural foraminal diameter and structures. MATERIAL AND METHODS: Five phantoms
      were imaged on CT with 3-mm axial slices followed by reformatted axial 3D-DESS
      and 3D-FISP sequences. In addition, 3D-DESS and 3D-FISP sequences of 20 healthy
      subjects were compared with regard to image quality, differentiation between
      vertebrae and discs, differentiation between discs and neural foramina, and
      differentiation between vertebrae and neural foramina. RESULTS: Compared with CT,
      3D-DESS and 3D-FISP sequences consistently underestimated the diameters of the
      neural foramina. The mean difference values for the 3D-DESS was 12.8%, compared
      to 9.5% for the 3D-FISP sequence. Concerning the in vivo studies, the 3D-DESS
      sequence was superior but not statistical significant to the 3D-FISP sequence
      with regard to image quality, differentiation between vertebrae and discs,
      differentiation between discs and neural formina, and identification of the nerve
      roots. CONCLUSION: The 3D-DESS sequence is moderately accurate in the evaluation
      of the neural foraminal size. Compared to the 3D-FISP sequence, the 3D-DESS
      sequence is compatible concerning the image quality, differentiation between the
      cervical vertebrae and discs, and between the discs and neural foramina.

PMID- 11972471
TI  - A rig for acquisition of standardized trabecular bone radiographs.
AB  - To assess osteoarthritic changes in knee joints a radiography rig for acquisition
      of standardized radiographs of trabecular bone has been developed. The rig
      contains a steel frame on castors, a turntable, a cassette holder frame,
      calibration Plexiglas sheets, body supports and points. It is used to lock the
      patient in a standardized position. A film cassette holder frame was also
      developed to reduce scattering of X-rays, and consequently the amount of noise in
      the radiographs. Calibration Plexiglas sheets were mounted on ball bearing slides
      to obtain radiographs without a calibration pattern (suitable for the analysis of
      trabecular bone texture) and radiographs containing a calibration pattern
      (suitable for the measurement of leg alignment).

PMID- 11972472
TI  - cAMP and cGMP do not mediate the vasorelaxation induced by iodinated radiographic
      contrast media in isolated swine renal arteries.
AB  - PURPOSE: Vasodilatation is a frequent side effect of radiographic contrast media,
      partially due to a direct effect on vascular smooth muscles. Our purpose was
      therefore to examine any possible implication of the cyclic adenosine
      monophospate (cAMP) and cyclic guanosine monophosphate (cGMP) pathways in
      contrast media induced vasorelaxation. MATERIAL AND METHODS: Isolated segments of
      swine renal arteries were precontracted with 10 microM phenylephrine and relaxed
      with iomeprol before and after blockade of the cAMP and cGMP pathways. RESULTS:
      80 mM and 160 mM of iomeprol significantly relaxed about 52% and 68% of the
      precontracted arterial rings, respectively. 10 microM of IBMX, a
      phosphodiesterase inhibitor, did not increase the relaxant effect of 80 mM
      iomeprol but increased the relaxations induced by 400 nM forskolin by about 1.9
      times (which stimulates the production of cAMP), and by 1 microM sodium
      nitroprusside (which stimulates the production of cGMP). 1 microM of H89 (an
      inhibitor of the cAMP-dependent protein kinase), was able to reduce the
      relaxation induced by 4 microM forskolin by about 2.5 times but had no
      significant effect on the relaxation induced by 160 mM iomeprol. 10 microM of ODQ
      (an inhibitor of the soluble guanylate cyclase), could reduce the relaxation
      induced by 10 microM of SNP but not the one induced by 160 mM iomeprol. Moreover,
      the absence of endothelial cells did not alter the relaxation induced by
      iomeprol. CONCLUSION: The activation of the cAMP and cGMP pathways are not
      involved in the in vitro relaxation induced by iomeprol in swine renal arteries.

PMID- 11972473
TI  - An unusual anatomical variation in cerebrovascular diagnosis.

PMID- 11972474
TI  - Do local Th2-driven or local IgE-mediated diseases exist without systemic IgE
      sensitization?

PMID- 11972476
TI  - Different methods of local allergen-specific immunotherapy.

PMID- 11972475
TI  - Specific immunotherapy--the induction of new IgE-specificities?

PMID- 11972477
TI  - Can we apply clinical studies to real life? Evidence-based recommendations from
      studies on development of allergic diseases and allergy prevention.

PMID- 11972478
TI  - Allergenic components of a novel food, Micronesian nut Nangai (Canarium indicum),
      shows IgE cross-reactivity in pollen allergic patients.
AB  - BACKGROUND: New foods may present a risk for food hypersensitive patients.
      Several examples exist of allergic reactions caused by cross-reactive plant
      derived foods, and new foods should be scrutinised before introducing them to the
      market. We have evaluated the clinical and serological relevance of cross
      reactivity between Nangai and pollen allergens. METHODS: Cross-reactivity was
      examined with Maxisorp RAST (radioallergosorbent test), RAST inhibition and
      Western blot, using sera from patients allergic to grass, birch and mugwort
      pollen. None of the patients reported having seen or eaten Nangai previously. To
      determine the biological and clinical relevance of the cross-reactivity,
      histamine release (HR) test, skin prick test (SPT) and food challenge were used.
      RESULTS: There was prevalence for reactivity against Nangai in the group of
      pollen allergic patients. This cross-reactivity seems to be related--at least in
      part--to carbohydrate epitopes. Three out of 12 patients tested with Nangai were
      positive upon open challenge, but using double blind placebo controlled food
      challenge (DBPCFC) this could not be confirmed in two patients. The biological
      effects of Nangai on allergic patients were confirmed using HR and SPT.
      CONCLUSION: The Nangai specific IgE found among pollen allergic patients
      addresses the need for control of new or changed foods before introduction to the
      market.

PMID- 11972479
TI  - Airway neutrophil inflammation in nonasthmatic patients with food allergy.
AB  - BACKGROUND: Patients with food allergy (FA) have been recently shown to develop
      bronchial hyperresponsiveness (BHR), despite the absence of any concomitant
      asthmatic manifestation. In order to explain this observation, we sought to
      examine the presence of a bronchial inflammation in induced sputum of
      nonasthmatic patients with FA. METHODS: Twelve nonasthmatic patients with FA
      (urticaria, digestive symptoms, anaphylaxis) were included in the study. Results
      were compared to these obtained from eight asthmatic patients without food
      allergy and eight healthy controls. Diagnosis of FA was based on double-blind
      placebo-controlled challenge. Sputum cells and fluid-phase eosinophil cationic
      protein (ECP), myeloperoxidase (MPO) and interleukin-8 (IL-8) were measured in
      induced sputum. BHR was evaluated using methacholine inhalation. RESULTS: Sputum
      from asthmatics, in comparison with the sputum of healthy subjects and patients
      with FA contained a higher proportion of eosinophils and higher levels of ECP (<
      0.001). In marked contrast, patients with FA exhibited an increased proportion of
      neutrophils and IL-8 in comparison with asthmatics and controls (P < 0.05 for
      neutrophils and P < 0.001 for IL-8). There was a significant correlation between
      sputum neutrophils and IL-8 (r = 0.68, P < 0.001). MPO levels were not different
      between the groups. There was a trend toward higher levels of IL-8 and ECP in
      food allergic patients with BHR in comparison with patients with FA without BHR.
      CONCLUSION: Our results demonstrate that a subclinical neutrophil airway
      inflammation is present in patients with food allergy free of clinical
      respiratory symptoms and that IL-8 may be an important mediator of this
      neutrophilia.

PMID- 11972480
TI  - Increased CD69 expression on peripheral blood eosinophils after specific
      inhalation challenge.
AB  - BACKGROUND: CD69 is a molecule expressed on human eosinophils after cytokine
      activation. Different studies have described the eosinophil activation, evaluated
      by CD69 expression, at the site of an allergic inflammation. In this study we
      evaluated the expression of CD69 on peripheral blood eosinophils after a specific
      inhalation challenge (SIC), in order to better define the state of activation of
      peripheral blood eosinophils after exposure to sensitizers. METHODS: CD69
      expression was evaluated by flow cytometry in nine asthmatic patients before and
      after a positive SIC with high or low molecular weight agents (pollens, house
      dust mites, Penicillia, isocyanates) and in 11 asthmatic patients who underwent
      an inhalation challenge with placebo. CD69 expression was evaluated at baseline,
      120 min, and 240 min after the SIC or the placebo. RESULTS: Baseline (before
      challenge) CD69 expression was comparable between the group of SIC positive
      patients and the placebo group. CD69 expression on peripheral eosinophils
      significantly increased 240 min after the challenge in positive SIC patients
      compared to placebo. In patients with a positive SIC the percentage of peripheral
      blood eosinophils significantly decreased at 120 and 240 min after the inhalation
      challenge with respect to the baseline. CONCLUSION: CD69 expression on peripheral
      blood eosinophils is significantly increased in asthmatic patients after exposure
      to the sensitizing agent. These data show that the effects of a bronchial
      stimulation are also detectable on peripheral blood eosinophils.

PMID- 11972481
TI  - Purification and partial characterization of the major allergen, Cav p 1, from
      guinea pig Cavia porcellus.
AB  - BACKGROUND: Allergic reaction to guinea pig has been recognized as a problem in
      domestic settings and work environments for many years. Until recently, limited
      information was available on the properties of guinea pig allergen(s). In this
      study the major allergen Cav p 1 was characterized and the N-terminal amino-acid
      sequence was determined. METHODS AND RESULTS: Sera from 40 patients with IgE
      mediated allergy to guinea pigs were investigated by means of immunoblotting
      using extracts prepared from guinea pig hair and urine. Three major allergens
      were identified within both sources with molecular weights (MW) of 8 kDa, 17 kDa
      and 20 kDa, respectively. From aqueous hair extracts the 20 kDa allergen (Cav p
      1) was purified to homogeneity by anion exchange chromatography and reverse-phase
      HPLC and the N-terminal amino-acid sequence was determined. On the basis of the
      15 residues, 57% identity was obtained from computer search with a sub-sequence
      of MUP (major urinary protein), a member of the lipocalin superfamily. Allergenic
      relationships among guinea pig allergens derived from various sources (hair and
      urine) or different animal species (mouse, rat, cat) were studied by ELISA
      inhibition assays. Neither urine of mouse, rat and cat, nor hair extracts of rat
      and cat produced appreciable inhibitions in guinea pig ELISA. CONCLUSION:
      Although the physicochemical characteristics of isolated Cav p 1 are very similar
      to those for other rodent allergens and furthermore partial sequence identity
      with Mus m 1 was found, it is clearly shown here to be an immunologically
      independent major allergen.

PMID- 11972482
TI  - Development of new IgE specificities to allergenic components in birch pollen
      extract during specific immunotherapy studied with immunoblotting and Pharmacia
      CAP System.
AB  - BACKGROUND: New IgE sensitizations to proteins in allergen extracts have been
      shown to occur during allergen-specific immunotherapy (IT). However little is
      known about the kinetics of the changes in antibody reactivities. METHODS: Twenty
      four allergic children and adults were treated with birch pollen rush IT (RIT).
      Fifteen matched patients served as allergic controls. Sera were obtained at
      regular intervals for up to three years and analyzed with immunoblotting and
      Pharmacia CAP System with recombinant (r) birch pollen allergens (rBet v 1, rBet
      v 2, and rBet v 4). RESULTS: All birch-allergic patients had specific IgE to the
      major birch pollen allergen Bet v 1, but only three had IgE to rBet v 2 and/or
      rBet v 4 at the beginning of the study. New IgE sensitizations developed in 65%
      of the birch RIT-treated patients when studied by immunoblotting. Twenty-nine
      percent of the patients developed new sensitizations to rBet v 2 and/or rBet v 4
      during RIT as measured by Pharmacia CAP System. Generally, new specific IgE
      reactivities occurred after at least one year of RIT, and only at low levels (< 1
      kUA/l). CONCLUSIONS: Sensitization to additional allergenic pollen components
      frequently occurs during prolonged birch RIT. However, the IgE levels are low and
      the clinical relevance is not known.

PMID- 11972484
TI  - Similar T helper Th2-like cytokine mRNA expression in vernal keratoconjunctivitis
      regardless of atopic constitution.
AB  - BACKGROUND: Many patients with vernal keratoconjunctivitis (VKC), a severe
      chronic allergic eye disease in children, exhibit IgE-sensitization, but about
      40% of cases lack this immunologic trait. As a disease factor in VKC, IgE is thus
      not fully understood. The aim of this study was to investigate whether there are
      any differences in the conjunctival cytokine messenger (m)RNA pattern related to
      IgE-sensitization in children suffering from VKC. METHODS: Tissue samples were
      obtained from 16 symptomatic VKC subjects with sub-tarsal disease and six control
      subjects. Expression of mRNA for interleukin (IL)-4, IL-5, IL-13, and interferon
      (IFN)-gamma was investigated with a semiquantitative reverse-transcriptase
      polymerase chain reaction (RT-PCR) technique. The presence of T cells, IgE+
      cells, mast cells, and eosinophils was analyzed with immunohistochemical methods.
      Allergen-specific IgE antibodies were assessed in serum and with skin prick
      testing. RESULTS: Ten out of the 16 VKC subjects showed evidence of IgE
      sensitization. No differences were detected for any tissue variable between VKC
      subjects with and without IgE-sensitization. Statistically significant increases
      over controls were found for both VKC groups with regard to all cell markers.
      CONCLUSIONS: The amount of messenger RNA encoding cytokines and inflammatory cell
      markers in VKC did not correlate with IgE-sensitization. Tissue changes in all
      patient samples were characterized by a prevalence of T cells, eosinophils, mast
      cells and cell-bound IgE molecules. However, the role of cell-bound IgE molecules
      in VKC patients lacking IgE-sensitization remains to be determined.

PMID- 11972483
TI  - Peripheral blood mononuclear cells from IgE- and non-IgE-associated allergic
      atopic eczema/dermatitis syndrome (AEDS) demonstrate increased capacity of
      generating interleukin-13 but differ in their potential of synthesizing
      interferon-gamma.
AB  - BACKGROUND: A subgroup of patients with allergic atopic eczema/dermatitis
      syndrome (AEDS) are known to have normal total and specific IgE levels and
      negative skin prick tests towards common environmental allergens. This form of
      the disease has been termed non-IgE-associated allergic AEDS. Although allergic
      mechanisms appear to be important, the pathogenesis of both IgE- and non-IgE
      associated forms of the disease is unknown. METHODS: We have compared the
      cytokine production pattern of peripheral blood mononuclear cells (PBMC) from IgE
      associated AEDS, non-IgE-associated AEDS, and normal control individuals. PBMC
      were stimulated with anti-CD3 and/or anti-CD28 monoclonal antibodies (mAb) and
      cytokine production was measured by immunoassays in supernatants of 24-h
      cultures. RESULTS: Compared to healthy subjects and non-IgE-associated AEDS
      patients, stimulated PBMC from IgE-associated AEDS patients produced less
      interferon (IFN)-gamma. However, stimulated PBMC from both IgE-associated AEDS
      and non-IgE-associated AEDS patients produced more interleukin (IL)-13 than PBMC
      from control individuals. Moreover, IL-5 production was significantly increased
      in non-IgE-associated AEDS but not in IgE-associated AEDS patients. CONCLUSIONS:
      The underlying mechanism leading to increased differentiation of T helper (Th) 2
      cells may involve a deficient capacity in producing IFN-gamma in IgE-associated
      AEDS but not in non-IgE-associated AEDS patients. IL-13 may be a key cytokine in
      the pathogenesis of both allergic forms of AEDS.

PMID- 11972485
TI  - Benzydamine: an alternative nonsteroidal anti-inflammatory drug in patients with
      nimesulide-induced urticaria.
AB  - BACKGROUND: Cutaneous adverse reactions to nonsteroidal anti-inflammatory drugs
      (NSAIDs), in particular urticaria/angiedema syndrome, represent a frequent
      problem in clinical practice. To date laboratory tests for the diagnosis of these
      adverse reactions are not available. A patient with an adverse drug reaction to
      NSAIDs needs an alternative drug to assume if necessary. Nimesulide is a highly
      prescribed nonsteroidal anti-inflammatory drug (NSAID) world-wide. It is also
      described as one of the most tolerated NSAID. In this paper we present data on
      the tolerability of benzydamine in nimesulide-sensitive patients. PATIENTS AND
      METHODS: One hundred and thirty-seven patients with nimesulide-induced urticaria
      were submitted to a single-blind, placebo-controlled peroral challenge with
      increasing doses of benzydamine. RESULTS: One hundred and thirty-four out of 137
      (98%) patients tolerated benzydamine without adverse effects, only three (2%)
      experienced immediate systemic urticaria (1 at the first dose and 2 at the second
      dose). CONCLUSION: Benzydamine is a well tolerated drug in patients with
      nimesulide-induced urticaria and it may represent a valid alternative NSAID in
      nimesulide-sensitive patients.

PMID- 11972486
TI  - Polymorphism 4G/5G in the plasminogen activator inhibitor-1 (PAI-1) gene is
      associated with IgE-mediated allergic diseases and asthma in the Czech
      population.
AB  - BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is a glycoprotein that
      belongs to the serine protease inhibitor superfamily and has an essential role in
      tissue remodeling after inflammation. Recently, a single base pair
      deletion/insertion (4G/5G) polymorphism of the PAI-1 gene has been associated
      with an increased risk of asthma in nuclear families from the UK. METHODS: The
      present study was thus conducted to determine the association of this
      polymorphism with the development of IgE-mediated asthma and other allergic
      diseases in the Czech population. A case-control approach was used in our study.
      DNA taken from subjects with clinically manifested asthma and other allergic
      diseases (n = 207) and from reference ethnically age-gender-matched unrelated
      subjects (n = 186) was examined for base deletions/insertions in the PAI-1 gene.
      RESULTS: A significant association (P = 0.0035) was observed between the PAI-1
      promoter polymorphism and IgE-mediated allergic diseases altogether. Furthermore,
      the 4G allele frequency was also significantly higher in the asthmatic patients
      than in the control group (P = 0.0148). CONCLUSIONS: Our findings support the
      idea that the 4G allele of the 4G/5G polymorphism in the PAI-1 gene may be a risk
      factor for IgE-mediated asthma and allergic diseases.

PMID- 11972487
TI  - An internet-based survey on the circumstances of food-induced reactions following
      the diagnosis of IgE-mediated food allergy.
AB  - BACKGROUND: Despite careful avoidance measures, food allergic patients have a
      significant risk of anaphylactic episodes. Risk situations need to be identified
      for more efficient preventive measures. METHODS: Responders to an internet-based
      survey on the awareness of food anaphylaxis were invited to relate the
      circumstances of their most severe reaction following the diagnosis of IgE
      mediated food allergy. Items of the questionnaire included the circumstances of
      the reaction and the treatment, as well as questions related to reactions
      occurring at specific categories of sites (i.e. home, schools, or restaurants).
      RESULTS: Fifty-one of the returned questionnaires (34.1%) corresponded to the
      study criteria. The median age of the subjects was 7 years (range 0.5-61), with
      33/51 (64.7%) being less than 16 years of age. Reactions were reported to peanuts
      (24/51; 47.1%), milk (12/51; 23.5%), tree nuts (6/51; 11.8%), fish and shellfish
      (5/51; 9.8%), and others (3/51; 5.8%). Reactions occurred at home (13/51; 25.5%),
      in restaurants (9/51; 17.6%), at school or daycare or kindergarten (8/51; 15.7%),
      at a relative or friend's home (7/51; 13.7%), at sites of leisure activities
      (6/51; 11.8%), at work (3/51; 5.9%), in church or a hospital ward (2/51; 3.9%
      each), or in a food store (1/51; 2.0%). In severe reactions (37/51; 72.5%)
      epinephrine was administered in 28/37 (75.7%) of the responders. Finally, while
      most reactions happened after ingestion of the food (40/51; 78.4%), others were
      reported after skin contact exclusively (8/51; 16%), or after inhalation (3/51;
      5.9%). CONCLUSION: Food induced-anaphylaxis in patients aware of their allergy
      happens most often at sites considered as safe (i.e. home, schools, workplace,
      hospitals). Better strategies to avoid accidental reactions include clear
      labelling of forbidden foods and increased information at all levels. These might
      dramatically reduce the risk of food-induced anaphylaxis in food allergy
      sufferers.

PMID- 11972488
TI  - Asthma and allergies at school--a Swedish national position paper.
AB  - The marked rise in allergies during the past decade has been increasingly
      perceptible for school personnel. A quarter of Swedish parents of children with
      allergies are unsatisfied with the school environment and how the schools are
      organized around their children. The Association of School Physicians has,
      together with six other medical, teaching and patient organizations, developed
      written guidelines for the management of asthma and allergies in Swedish schools.
      The aim was to regulate the responsibility of the school and its personnel for
      students with asthma and allergies, and to strengthen safety arrangements within
      schools. A secondary aim was to describe how the curriculum, teaching equipment,
      excursions, and other school activities, could be arranged appropriately and
      safely for students with asthma and allergies. Five-hundred copies of the
      document were circulated to all of Sweden's municipalities, county councils and
      pediatric departments. There was general agreement regarding the schools'
      responsibility that no child should risk becoming ill or having exacerbation of
      symptoms due to conditions at school. Recommendations regarding smoking on school
      premises and the use of perfumes were criticised. The strength of this document
      is that all organizations actively involved with schools have agreed upon these
      recommendations. This document serves to suggest a minimum level of activities
      thus ensuring that even students with asthma and allergies will receive
      appropriate schooling.

PMID- 11972490
TI  - Delayed hypersensitivity to piperacillin.

PMID- 11972491
TI  - Allergy to azufaifa fruit and latex.

PMID- 11972492
TI  - Occupational asthma due to mitoxantrone.

PMID- 11972493
TI  - Oral latex glove allergy.

PMID- 11972494
TI  - Cytokines and Th2 cells in AEP of smoking.

PMID- 11972495
TI  - TPIS--an IgE-binding wheat protein.

PMID- 11972501
TI  - Urolithiasis through the ages.

PMID- 11972496
TI  - Reduction of allergen by occlusive covering.

PMID- 11972502
TI  - Urolithiasis in pregnancy. I: pathophysiology, fetal considerations and
      diagnosis.

PMID- 11972503
TI  - Urolithiasis in pregnancy. II: management.

PMID- 11972504
TI  - Antibiotic prophylaxis for prostate biopsy.

PMID- 11972505
TI  - Cutaneous reaction to low-molecular-weight heparin.

PMID- 11972506
TI  - Anaplastic large cell lymphoma of the parietal bone.

PMID- 11972507
TI  - Impaired gut function as risk factor for invasive candidiasis in neutropenic
      patients.

PMID- 11972508
TI  - The spleen.

PMID- 11972509
TI  - Transfusion-associated graft-versus-host disease.

PMID- 11972510
TI  - Thalidomide treatment in myelofibrosis with myeloid metaplasia.
AB  - Myelofibrosis with myeloid metaplasia (MMM) is uniquely characterized by
      macroscopic bone marrow stromal changes that are believed to be both reactive and
      cytokine mediated. Furthermore, a prognostically detrimental increase in bone
      marrow angiogenesis has recently been demonstrated. These observations suggest a
      potential therapeutic role for agents that are inhibitory to angiogenesis as well
      as cytokines that are pathogenetically implicated in MMM. In a prospective study
      of 15 patients with MMM, thalidomide treatment, starting at a dose of 200 mg/d,
      resulted in increased platelet counts (12 of 15 patients), increased haemoglobin
      level (3 of 15), a modest decrease in spleen size (3 of 12), increased bone
      marrow megakaryopoiesis (5 of 9) and decreased bone marrow angiogenesis (2 of 9).
      Undesirable haematological effects included pericardial extramedullary
      haematopoiesis in one patient, marked leucocytosis in two patients and extreme
      thrombocytosis in three patients. The thrombocytosis occurred in both patients
      with post-thrombocythaemic myeloid metaplasia (PTMM) and was also associated with
      higher baseline levels of circulating CD34+ cells. Previously described
      toxicities of thalidomide were seen in the majority of patients and dose
      escalation to 400 mg/d was permitted in only two patients. In contrast, toxicity
      related dose reductions to 50 mg/d did not appear to lessen drug efficacy. We
      conclude that thalidomide has both beneficial and potentially adverse biological
      activity in MMM. A lower dose of the drug might be more tolerable without
      compromising therapeutic value. Patients with PTMM and/or markedly increased
      circulating CD34+ cell counts might be susceptible to thalidomide-induced
      thrombocytosis.

PMID- 11972511
TI  - Optimizing dendritic cell-based immunotherapy in multiple myeloma.
AB  - Vaccination with idiotype protein-pulsed dendritic cells (DCs) has been explored
      in multiple myeloma and the results have been disappointing. These studies used
      immature DCs, which are less potent at activating T cells and could differentiate
      to macrophages once the cytokines were withdrawn. After intravenous
      administration, DCs accumulate in the lungs and liver for up to 48 h, thus
      reducing their potential to migrate to lymphoid organs and interact with T cells.
      To improve the efficacy of DC vaccination in myeloma, we investigated the use of
      idiotype-pulsed mature DCs administered subcutaneously. Five patients (three IgG
      and two IgA myeloma) with stable partial remission following high-dose
      chemotherapy were enrolled. DC vaccines were administered three times at 2-week
      intervals at least 4 months post transplantation. Idiotype-specific T-cell
      responses, detected using enzyme-linked immunospot (ELISPOT) (four patients) and
      proliferation (two patients) assays, were elicited in four and anti-idiotypic B
      cell responses in all five patients. The cytokine-secretion profile of activated
      T cells demonstrated a type-1 response. A 50% reduction in serum M-component was
      observed in one immunologically responding patient that persisted for 6 months
      and stable disease (for 6 months) resulted in the other three patients. The
      remaining patient without an immune response to the vaccination relapsed. No
      major side-effects were noted. Thus, subcutaneous administration of idiotype
      pulsed mature DCs induced idiotype-specific T- and B-cell responses. Current
      efforts are geared towards optimizing the conditions of DC generation and
      administration, and the development of in vitro assays to monitor the
      cytotoxicity of the T cells.

PMID- 11972512
TI  - Treatment of infants with lymphoblastic leukaemia: results of the UK Infant
      Protocols 1987-1999.
AB  - One hundred and twenty-six infants with acute lymphoblastic leukaemia (ALL) were
      treated on two consecutive protocols, Infant 87 (n = 40) and Infant 92 (n = 86),
      in an attempt to improve the poor prognosis of this disease. Both included
      intensive induction and consolidation with intrathecal and high-dose systemic
      therapy for central nervous system (CNS) protection. Intensification therapy was
      modified and high-dose chemotherapy with bone marrow transplantation in first
      remission was permitted in Infant 92. Four-year event-free survival was superior
      in Infant 92 (33%; 95% CI 23-44%) compared with Infant 87 (22.5%; 95% CI 12-37%)
      (P = 0.04) and survival at 4 years was also superior, 46% (95% CI 35-57%) c.f.
      32.5% (95% CI 20-48%) (P = 0.01), largely as a result of a significant reduction
      in remission deaths. Twelve patients in Infant 92 underwent bone marrow
      transplantation (BMT) in first remission, but their survival was no better than
      that of patients receiving chemotherapy. Multivariate analysis of prognostic
      factors showed the adverse influence of younger age, CNS involvement at diagnosis
      and a high initial leucocyte count, but not of CD10 expression. Cytogenetic
      analysis, available in 93% of patients in Infant 92, showed that 67% had
      chromosomal rearrangements involving 11q23 of which 39% had the translocation
      t(4;11) (q21;q23). There was no significant difference in event-free survival
      between cytogenetic subgroups, although no children under 6 months of age with
      11q23 abnormalities, other than the t(4;11), survived. In conclusion, infants
      with lymphoblastic leukaemia remain a high-risk group, but it is unclear whether
      their adverse prognosis can be attributed to unfavourable cytogenetics alone. The
      role of high-dose therapy and BMT in first remission remains uncertain.

PMID- 11972513
TI  - Low frequency of clonotypic Ig and T-cell receptor gene rearrangements in t(4;11)
      infant acute lymphoblastic leukaemia and its implication for the detection of
      minimal residual disease.
AB  - Infant t(4;11) acute lymphoblastic leukaemia (ALL) is a rare but cytogenetically
      well defined subgroup of immature B-cell precursor (BCP) ALL. To date, the
      configuration of their antigen receptor genes has not been studied in a large
      group of patients so far. In this study on 27 t(4;11) infant ALL, we have used
      standardized primer sets for the detection of all incomplete and complete
      immunoglobulin (Ig) heavy chain (IGH) rearrangements, as well as for the Ig light
      chain kappa (IGK), T-cell receptor delta (TCRD) and gamma (TCRG) rearrangements
      that are most common in childhood BCP ALL. Only 52% of cases displayed clonotypic
      antigen receptor gene rearrangements (IGH in 48%, IGK, TCRD and TCRG in 12%, 41%
      and 6% respectively). This low frequency suggests, together with the findings of
      predominantly incomplete DJh joins and monoallelic IGH rearrangements, that they
      are derived from an immature progenitor cell. As 48% of the t(4;11) infant ALL
      cases had no detectable antigen receptor gene rearrangements that could be used
      for minimal residual disease (MRD) analysis, we established an expression
      independent, leukaemia-specific polymerase chain reaction (PCR) using the genomic
      sequence of the MLL-AF4 fusion genes. This method had high sensitivity and
      specificity and resulted in identical estimations of tumour loads when compared
      with IGH targets. Thus, genomic MLL-AF4 fusion genes are a good alternative
      target for the analysis of MRD in patients with t(4;11) leukaemias.

PMID- 11972514
TI  - Rearrangement of the BCL6 locus at 3q27 is an independent poor prognostic factor
      in nodal diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphomas (DLBCL) are a heterogeneous group of tumours,
      varying in clinical features, immunophenotype and cytogenetics. The aim of this
      study was to investigate the prognostic significance of BCL6 gene rearrangement
      at the 3q27 locus in patients with primary nodal disease, and to examine
      interrelationships with immunophenotype and International Prognostic Index (IPI).
      We have developed a fluorescent in situ hybridization (FISH)-based technique for
      the retrospective analysis of the effect of BCL6 gene rearrangements on survival,
      using nuclei extracted from paraffin-embedded tissue. FISH results were obtained
      in 111 presentation cases of nodal DLBCL. The IPI was calculated and each case
      was stained immunocytochemically for BCL6, BCL2 and CD10. 3q27 rearrangements
      were detected in 25% of cases. BCL2 protein and a germinal centre (GC) phenotype
      (defined as CD10+, BCL6+) were expressed in 56% and 41% of cases respectively. In
      multivariate analysis, rearrangement of 3q27 and BCL2 expression and the absence
      of a GC phenotype were associated with a poor prognosis. These factors can be
      used in conjunction with the IPI to improve risk stratification in nodal DLBCL.

PMID- 11972515
TI  - Liposomal encapsulation diminishes daunorubicin-induced generation of reactive
      oxygen species, depletion of ATP and necrotic cell death in human leukaemic
      cells.
AB  - In this study, we tested the mechanisms of daunorubicin (DNR)- and the liposomal
      encapsulated daunorubicin (DaunoXome or DNX)-induced killing in three human
      leukaemic cell lines, K562, K/Bax and CEM. DNX showed less cytotoxicity in
      leukaemic cells than conventional DNR. The intracellular accumulation of DNX was
      10 times less than conventional DNR during exposure to drugs for up to 5 h. Cell
      cycle analysis indicated that DNR induced concentration-dependent G2/M arrest,
      apoptosis and necrosis. However, DNX induced G2/M arrest and apoptosis but not
      necrotic cell death, even at a higher concentration. DNR- or DNX-induced
      activation of caspase-9 and -3 was detected at concentrations that induced
      apoptosis and necrosis. The sensitivity of leukaemic cells to DNR- and DNX
      induced apoptosis correlated with the activation of caspases and the reduction of
      mitochondrial membrane potential (DeltaPsim), but not the depletion of ATP and
      the generation of reactive oxidative species (ROS). DNX did not provoke ROS
      generation and ATP depletion in leukaemic cells. We conclude that the liposomal
      encapsulation of DNR restricts the intracellular accumulation speed and therefore
      diminishes ROS generation, ATP depletion and necrotic cell death. This may have
      implications for the cause of cardiotoxicity seen with DNR, its main dose
      limiting step.

PMID- 11972516
TI  - In vitro and in vivo effectiveness of arsenic trioxide against murine T-cell
      prolymphocytic leukaemia.
AB  - T-cell prolymphocytic leukaemia (T-PLL) is a rare form of mature T-cell leukaemia
      that is generally resistant to conventional chemotherapy. Mice transgenic for
      MTCP1 develop leukaemia similar to human T-PLL, providing a model useful for
      testing therapeutics. We here evaluated the potential effectiveness of arsenic
      trioxide (ATO) in murine T-PLL. In vitro, ATO consistently reduced the viability
      of murine T-PLL cells at a clinically achievable concentration (1 micromol/l).
      The percentage of viable cells after 24 h was 77 +/- 4%, 56 +/- 6%, 31 +/- 7%
      with 0 micromol/l, 0.5 micromol/l and 1 micromol/l ATO respectively. ATO
      cytotoxicity was enhanced by ascorbic acid (125 micromol/l). Mice were then
      treated with ATO (5 microg/g/d intra peritoneally, 5 d per week) or saline for 4
      weeks, starting 14 d after tumoral engraftment. The appearance of lymphocytosis
      and splenomegaly was delayed in the group treated with ATO and survival was
      significantly prolonged (mean survival in days: 57.6 +/- 0.8 for ATO versus 45 +/
      0 for saline, P < 10-4). No additional effect was observed in vivo by combining
      ATO with ascorbic acid (500 microg/g/d, 5 d per week, intra peritoneally). These
      findings provide support for clinical trials to test therapeutic effects of ATO
      for human T-PLL.

PMID- 11972517
TI  - Abdominal infections in patients with acute leukaemia: a prospective study
      applying ultrasonography and microbiology.
AB  - A prospective study of 62 chemotherapy-induced neutropenic episodes in patients
      with acute leukaemia was conducted to determine the incidence and causes of
      abdominal infections, and to assess the diagnostic value of the combined use of
      ultrasonography (US) and microbiology. Each patient underwent US of liver,
      gallbladder and complete bowel before chemotherapy, on days 2-4 after the end of
      chemotherapy and in cases of fever, diarrhoea or abdominal pain. US was combined
      with a standardized clinical examination and a broad spectrum of microbiological
      investigations. From January to August 2001, 243 US examinations were performed.
      The overall incidence of abdominal infectious diseases was 17.7% (11 out of 62,
      95% confidence interval (CI): 9-29%). Four patients (6.5%) developed neutropenic
      enterocolitis; two of them died, two survived. Bowel wall thickening (BWT) > 4 mm
      in these four patients ranged from 5.8 to 23.6 mm and was detected only in one
      patient with mucositis. In three other patients (4.8%) Clostridium difficile, and
      in one patient (1.6%) Campylobacter jejuni, caused enterocolitis without BWT.
      Cholecystitis was diagnosed in three patients (4.8%) and hepatic candidiasis was
      strongly suspected in one patient. Abdominal infections caused by gastroenteritis
      viruses, cytomegalovirus (CMV) or Cryptosporidium were not observed. We conclude
      that in neutropenic patients with acute leukaemia receiving chemotherapy: (i) BWT
      is not a feature of chemotherapy-induced mucositis and should therefore be
      considered as sign of infectious enterocolitis; (ii) viruses, classic bacterial
      enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Aeromonas,
      Vibrio subsp., enterohaemorrhagic Escherichia coli) and Cryptosporidium have a
      very low incidence; and (iii) abdominal infections may be underestimated when US
      is not used in every patient with abdominal pain.

PMID- 11972518
TI  - High level of microsatellite instability but not hypermethylation of mismatch
      repair genes in therapy-related and secondary acute myeloid leukaemia and
      myelodysplastic syndrome.
AB  - Microsatellite instability (MSI) is associated with defects in the DNA mismatch
      repair (MMR) system, such as mutation or epigenetic silencing of the genes by
      promoter hypermethylation. We investigated the presence of MSI and promoter
      hypermethylation of hMLH1 and hMSH2 genes in 82 patients (68 acute myeloid
      leukaemia, AML; 14 myelodysplastic syndromes, MDS). Twelve separate
      microsatellite loci, including three mononucleotide repeat markers, were used.
      Mutator phenotype (RER+) was detected in 20 AML (29.4%) and 3 MDS (21.4%)
      patients. RER+ rate was much higher in the therapy-related and secondary cases
      compared with the de novo cases. Three out of 7 (42.9%) secondary (s-AML) and 8
      out of 17 (47.1%) therapy-related (t-AML) showed RER+ in comparison with 9 out of
      44 (20.5%) de novo cases. Similar rates were detected in MDS patients (2/2
      therapy-related and 1/12 de novo). The promoter hypermethylation was found in
      three hMLH1 (3.7%) and two hMSH2 (2.4%) genes. All these five patients had AML
      and were older than 60 years of age. Two of them had s-AML and one had t-AML.
      RER+ was detected in three of these five patients. Our data suggest that genetic
      instability is associated with AML and MDS, especially t-AML and s-AML. In
      addition, our results indicate that the hMSH2 and hMLH1 promoter hypermethylation
      is not a common event in these malignancies, but may play a role in the
      development of AML in elderly patients.

PMID- 11972519
TI  - Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's
      disease.
AB  - Biological and clinical studies have shown that Hodgkin's disease (HD) can be
      divided into two major categories, termed nodular lymphocyte predominance HD (NLP
      HD) and classic HD (CHD). Within CHD four subtypes have been distinguished:
      nodular sclerosis, mixed cellularity, lymphocyte rich and lymphocyte depletion.
      To refine the histogenesis of the pathological spectrum of HD, 75 CHD and 13 NLP
      HD were analysed for the expression pattern of MUM1/IRF4 (Multiple Myeloma
      1/Interferon Regulatory Factor-4), a lymphocyte-specific member of the IRF
      family, that is expressed by late centrocytes and post-germinal centre (GC) B
      cells. MUM1 reacted with Hodgkin's and Reed-Sternberg (HRS) cells of all CHD
      cases (75/75 cases), with a moderate to strong staining intensity. Conversely,
      lymphocyte and histiocyte (L & H) cells, the putative tumour cells of NLP HD,
      were negative for MUM-1 expression (9/13 cases) or displayed a weak reactivity
      for the antigen in < 10% neoplastic cells (4/13 cases). With respect to HD
      microenvironment, NLP HD displayed numerous MUM1-positive T lymphocytes located
      in close proximity to L & H cells whereas, in CHD, MUM1-positive T lymphocytes
      appeared to be distributed randomly with no specific relationship with HRS cells.
      Overall, this study shows that MUM1 expression differs in L & H cells versus HRS
      cells, corroborating the notion that NLP HD and CHD represent different stages of
      B-cell differentiation. As MUM1-positive T lymphocytes form rosettes around
      tumour cells of NLP HD, but not of CHD, these data point also to differences in
      the microenvironment of NLP HD and CHD, and postulate an interactive role of MUM1
      positive T lymphocytes with L & H cells.

PMID- 11972520
TI  - A novel cell line derived from de novo acute myeloblastic leukaemia with
      trilineage myelodysplasia which proliferates in response to a Notch ligand, Delta
      1 protein.
AB  - A novel human leukaemia cell line, designated TMD7, was established from blast
      cells of a patient with de novo acute myeloblastic leukaemia with trilineage
      myelodysplasia (AML/TLD). As seen in the original blast cells, TMD7 cells
      expressed CD7, CD13, CD33 and CD34 and showed an abnormal karyotype containing 
      5, -7, -8, der(16)t(10;16)(q22;q13). The cells proliferated without added growth
      factors. Growth was stimulated with the addition of granulocyte colony
      stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF) and interleukin
      3. Differentiation was not observed with the addition of various cytokines. As a
      cell line derived from AML/TLD has not been reported, TMD7 will be a useful tool
      as a model of AML/TLD cells. Recently, it was reported that the Notch system has
      crucial roles to regulate the self-renewal and differentiation of haematopoietic
      stem cells. We found that TMD7 cells expressed Notch-1 and Notch-2 mRNA. The
      exposure to recombinant Delta-1 protein, which was one of the Notch ligands,
      significantly stimulated the growth of TMD7 cells. This is the first human cell
      line which was shown to proliferate in response to Delta-1, without artificially
      expressed Notch protein. Therefore, TMD7 will also be a useful tool to study the
      mechanism of the Notch-Notch ligand interaction.

PMID- 11972522
TI  - Interleukin 6 and tumour necrosis factor alpha serum levels in monoclonal
      gammopathy of undetermined significance.
AB  - The objectives of the present study were to compare the interleukin 6 (IL-6) and
      tumour necrosis factor-alpha (TNF-alpha) serum levels of individuals with
      monoclonal gammopathy of undetermined significance (MGUS) with those of healthy
      controls, and to ascertain the predictor value of these cytokines in the
      evolution from MGUS to multiple myeloma. After a median follow-up of 7 years from
      the initial cytokine measurements, nine patients with MGUS have evolved to a
      malignant condition. The actuarial probability of malignant transformation in
      patients with increased IL-6 and TNF-alpha was not significantly higher than in
      those with normal values.

PMID- 11972521
TI  - Pneumocystis carinii pneumonia in patients with malignant haematological
      diseases: 10 years' experience of infection in GIMEMA centres.
AB  - A retrospective survey was conducted over a 10-year period (1990-99) among 52
      haematology divisions in order to evaluate the clinical and laboratory
      characteristics and outcome of patients with proven Pneumocystis carinii
      pneumonia (PCP) complicating haematological diseases. The study included 55
      patients (18 with non-Hodgkin's lymphoma, 10 with acute lymphoblastic leukaemia,
      eight with acute myeloid leukaemia, five with chronic myeloid leukaemia, four
      with chronic lymphocytic leukaemia, four with multiple myeloma, three with
      myelodysplastic syndrome, two with myelofibrosis and one with thalassemia) who
      developed PCP. Among these, 18 (33%) underwent stem cell transplantation; only
      two received an oral prophylaxis with trimethroprim/sulphamethoxazole. Twelve
      patients (22%) developed PCP despite protective isolation in a laminar airflow
      room. The most frequent symptoms were: fever (86%), dyspnoea (78%), non
      productive cough (71%), thoracic pain (14%) and chills (5%); a severe hypoxaemia
      was present in 39 patients (71%). Chest radiography or computerized tomography
      showed interstitial infiltrates in 34 patients (62%), alveolar infiltrates in 12
      patients (22%), and alveolar-interstitial infiltrates in nine patients (16%).
      Bronchoalveolar lavage was diagnostic in 47/48 patients, induced sputum in 9/18
      patients and lung biopsy in 3/8 patients. The diagnosis was made in two patients
      at autopsy. All patients except one started a specific treatment (52 patients
      trimethroprim/sulphamethoxazole, one pentamidine and one dapsone). Sixteen
      patients (29%) died of PCP within 30 d of diagnosis. Multivariate analysis showed
      that prolonged steroid treatment (P < 0.006) and a radiological picture of
      diffuse lung involvement (P < 0.003) were negative diagnostic factors.

PMID- 11972523
TI  - Three parameters, plasma thrombopoietin levels, plasma glycocalicin levels and
      megakaryocyte culture, distinguish between different causes of congenital
      thrombocytopenia.
AB  - Fourteen children with congenital thrombocytopenia were analysed in order to
      unravel the mechanisms underlying their thrombocytopenia and to evaluate the
      value of new laboratory tests, namely measurement of plasma thrombopoietin (Tpo)
      and glycocalicin (GC) levels and analysis of megakaryocytopoiesis in vitro. Three
      groups of patients were included. The first group (n = 6) was diagnosed with
      congenital amegakaryocytic thrombocytopenia. They had no megakaryocytes in the
      bone marrow, three out of four patients showed no megakaryocyte formation in
      vitro, and all had high Tpo and low GC levels. Mutations in the thrombopoietin
      receptor gene, c-mpl, were the cause. The second group of patients (n = 3) had
      normal Tpo and severely decreased GC levels. In bone marrow, normal to increased
      numbers of atypical, dysmature megakaryocytes were present. In vitro
      megakaryocyte formation was quantitatively normal. A defect in final
      megakaryocyte maturation and subsequent (pro-)platelets may be the cause of the
      thrombocytopenia. The patients in the third group (n = 5) had Wiskott-Aldrich
      syndrome (WAS). They had normal Tpo and GC levels and normal megakaryocyte
      formation both in vivo and in vitro. This corresponded with the generally
      accepted hypothesis that thrombocytopenia in WAS is due to increased platelet
      turnover. In conclusion, different causes of congenital thrombocytopenia can be
      distinguished using three parameters: Tpo and GC plasma levels and in vitro
      analysis of megakaryocytopoiesis. Therefore, these parameters may be helpful in
      early diagnosis of different forms of congenital thrombocytopenia.

PMID- 11972524
TI  - Mean platelet volume is an independent risk factor for myocardial infarction but
      not for coronary artery disease.
AB  - After rupture of an arteriosclerotic plaque in a coronary artery, platelets play
      a crucial role in the subsequent thrombus formation, leading to myocardial
      infarction. An increased mean platelet volume (MPV), as an indicator of larger,
      more reactive platelets, may represent a risk factor for myocardial infarction.
      However, this hypothesis is still controversial and most studies addressing the
      role of MPV were performed comparing patients suffering from myocardial
      infarction with healthy controls. We intended to identify patients at high risk
      of suffering myocardial infarction in a group of patients with known coronary
      artery disease. One hundred and eighty-five consecutive patients with stable
      coronary artery disease were compared with 188 individuals who had suffered
      myocardial infarction. Patients within the highest quintile of MPV (> or = 11.6
      fl) had a significantly higher risk of experiencing a myocardial infarction
      compared with patients within the lowest quintile (OR = 2.6, 95% CI 1.3-5.1) in a
      multivariate analysis that included sex, age, body mass index, hyperlipidaemia,
      hypertension, smoking and diabetes mellitus. Our results indicate that patients
      with pre-existing coronary artery disease and an increased MPV (> or = 11.6 fl)
      are at higher risk of myocardial infarction. These patients can be easily
      identified during routine haematological analysis and could possibly benefit from
      preventive treatment.

PMID- 11972525
TI  - Human platelet antigen 1 (HPA 1) genotyping with 5' nuclease assay and sequence
      specific primers reveals a single nucleotide deletion in intron 2 of the HPA 1a
      allele of platelet glycoprotein IIIa.
AB  - We have established a 5' nuclease assay (5' NA) for human platelet antigen (HPA)
      1a/b allelic discrimination. The assay is based on the simultaneous amplification
      and detection of the two targets in a one-tube system. The results are read
      optically, immediately after termination of the polymerase chain reaction (PCR),
      and no post-PCR processing is necessary. This genotyping procedure is less time
      consuming and cheaper than our conventional sequence-specific primer PCR (SSP
      PCR), which is run as a two-tube test, with verification of the results after
      electrophoresis in agarose gel. The reduction of analytical steps, simplification
      of the procedure and potential for automation were important advantages for our
      choice of system. This test system is more suitable for large-scale testing and
      fits better for our screening programme for HPA 1bb determination. DNA from 1093
      individuals were tested in parallel with the SSP-PCR and the 5' NA. One thousand
      and ninety-one samples gave identical results in SSP-PCR and 5' NA. Upon repeated
      testing, two samples consistently came out as HPA 1bb in SSP-PCR and HPA 1ab in
      5' NA. DNA sequencing revealed a defect located in an intronic area that
      corresponds to the consensus primer used for the SSP-PCR HPA 1a typing.

PMID- 11972526
TI  - Red blood cells from patients with homozygous sickle cell disease provide a
      catalytic surface for factor Va inactivation by activated protein C.
AB  - The structure of red blood cell (RBC) membranes in homozygous sickle cell disease
      (SCD) is significantly disturbed, with an increased exposure of
      aminophospholipids (phosphatidylserine and phosphatidylethanolamine) at the outer
      surface, responsible for a procoagulant activity of SS RBCs. Aminophospholipids
      are known not only to promote procoagulant reactions, but also to support
      inhibition of blood coagulation by the protein C system. The aim of the present
      study was to examine whether SS RBCs could serve as a catalytic surface for the
      inactivation of factor Va by activated protein C (APC). Venous blood was obtained
      from 19 consecutive SS patients and 13 controls (AA). In all SS patients, the
      amount of phosphatidylserine exposed at the outer surface of RBCs was increased
      compared with controls, as demonstrated by a prothrombinase assay. In addition,
      SS RBCs significantly (P < 0.0001) increased the rate of FVa inactivation by APC:
      the mean values (and ranges) of the factor Va inactivation rates were 30 (0-57)
      vs 9.5 (0-32) mmol Vai/min/mol APC for SS RBCs and normal RBCs respectively. Our
      results indicate that SS RBCs provide a catalytic surface for the negative
      control of blood coagulation, which may partially control the procoagulant
      activity of these cells.

PMID- 11972527
TI  - Cell-specific abnormal prenylation of Rab proteins in platelets and melanocytes
      of the gunmetal mouse.
AB  - The mutant gunmetal mouse exhibits reduced rates of platelet synthesis,
      abnormalities of platelet alpha and dense granules and hypopigmentation. Several
      of these features resemble those of human alpha/delta platelet storage pool
      disease, grey platelet syndrome and Hermansky-Pudlak syndrome. Gunmetal mice have
      reduced levels of Rab geranylgeranyltransferase (RabGGTase), which adds
      lipophilic prenyl groups to the carboxyl terminus of Rab proteins. The degree of
      prenylation and the subcellular distribution of several Rab proteins were
      evaluated in mutant platelets, melanocytes and other tissues. Significant
      deficits in prenylation and membrane binding of most Rabs were observed in
      platelets and melanocytes. In contrast, minimal alterations in Rab prenylation
      were apparent in several other gunmetal tissues despite the fact that RabGGTase
      activity was equally diminished in these tissues. The mutant tissue-specific
      effects are probably due to increased concentrations of Rab proteins in platelets
      and melanocytes. These experiments show that Rab proteins are differentially
      sensitive to levels of RabGGTase activity and that normal platelet synthesis,
      platelet organelle function and normal pigmentation are highly sensitive to the
      degree of prenylation and membrane association of Rab proteins. Further, the
      tissue-specific effects of the gunmetal mutation suggest that RabGGTase is a
      potential target for therapy of thrombocytosis.

PMID- 11972528
TI  - Flow cytometry analysis of platelet cyclooxygenase-2 expression: induction of
      platelet cyclooxygenase-2 in patients undergoing coronary artery bypass grafting.
AB  - There are conflicting reports about the expression of cyclooxygenase (COX)-2 in
      human platelets. The present study describes a flow cytometric method for the
      measurement of platelet COX. Both COX-1 and COX-2 were shown to be expressed in
      platelets from patients undergoing a coronary artery bypass graft. There was a
      significant increase in COX-2 expression at day 5 as compared with pre-surgery
      values (mean fluorescence 12.31 +/- 0.88 versus 9.15 +/- 0.88; means +/- SEM, n =
      7, P < 0.05), whereas COX-1 levels did not change (13.45 +/- 1.11 versus 12.38 +/
      1.41; n = 7, P > 0.05).

PMID- 11972529
TI  - Translocations of 14q32 and deletions of 13q14 are common chromosomal
      abnormalities in systemic amyloidosis.
AB  - Systemic monoclonal immunoglobulin light chain amyloidosis (AL) is associated
      with clonal plasma cell dyscrasias that are often subtle and non-proliferating.
      AL shares numerical chromosomal changes with multiple myeloma (MM) and monoclonal
      gammopathy of undetermined significance (MGUS). Illegitimate translocations
      involving the immunoglobulin heavy chain gene (IGH) at 14q32 and deletions of the
      long arm of chromosome 13, [del(13q)], commonly occur in MM, MGUS and plasma cell
      leukaemia. In AL IGH rearrangements have been identified but, to date, there are
      no reports of del(13q). In this study of 32 patients with AL, 24 with systemic
      and eight with localized disease, translocations involving IGH and del(13q) were
      found using dual-colour interphase fluorescence in situ hybridization (FISH). IGH
      translocations were observed in 11 patients (37% overall and in 46% with systemic
      disease), of which nine had the IGH/CCND1 fusion from t(11;14)(q13;q32). Two
      showed IGH translocations other than the t(11;14) or t(4;14)(p16;q32). In one of
      these patients a breakpoint within the constant region of IGH between Calpha1 and
      Calpha2 was indicated. In the second a deletion covering Calpha1 and Calpha2
      accompanied the translocation. Ten patients (27% overall and 33% of those with
      systemic disease) showed del(13q). The gain or loss of IGH and CCND1 signals
      provided evidence of numerical chromosomal changes in three patients.

PMID- 11972530
TI  - Effect of VDR polymorphisms on growth and bone mineral density in homozygous beta
      thalassaemia.
AB  - We examined the effect of vitamin D receptor (VDR) polymorphisms at exon 2 (FokI)
      and intron 8 (BsmI) on the stature and bone mineral density at femoral neck
      (FBMD) and lumbar spine (LBMD) in 108 prepubertal and pubertal homozygous beta
      thalassaemic patients, regularly treated. We found significantly shorter stature
      and lower LBMD and FBMD in all patients with CC VDR genotype, and significant
      shorter height and lower LBMD in prepubertal and pubertal female patients with BB
      VDR genotype. Because homozygous CC and BB VDR genotypes influence Vitamin D
      activity, they can be considered additional risk factors for bone disease in beta
      thalassaemia.

PMID- 11972531
TI  - Belated diagnosis in three patients with rifampicin-induced immune haemolytic
      anaemia.
AB  - We report three patients who developed haemolysis following rifampicin treatment.
      Initially, autoimmune haemolytic anaemia (AIHA) of the warm type and/or an acute
      haemolytic transfusion reaction (AHTR) was suggested. The direct antiglobulin
      tests (DAT) were strongly positive for IgG and C3d, and tests for rifampicin
      dependent antibodies were positive in all three cases, featuring C-specificity in
      one case. The outcome was fatal in two out of the three cases, presumably due to
      belated diagnosis. This shows that rifampicin may stimulate the production of
      autoantibodies (aab) and/or drug-dependent antibodies (ddab), and that the
      resulting haemolytic syndrome bears similarities with AIHA and AHTR.

PMID- 11972532
TI  - Early and late invasive pneumococcal infection following stem cell
      transplantation: a European Bone Marrow Transplantation survey.
AB  - Streptococcus pneumoniae (S. pneumoniae) may cause severe and lethal infections
      months and years following stem cell transplantation (SCT). In a prospective
      survey over a 3.5-year period, we assessed the incidence, risk factors and
      outcome for invasive pneumococcal infection (IPI) following SCT. Fifty-one
      episodes of IPI were reported: 43 episodes after bone marrow transplantation
      (BMT) and 8 after peripheral blood stem cell transplantation (PBSCT); 35 after
      allogeneic SCT and 16 after autologous SCT. Seven IPI episodes, all bacteraemias,
      were defined as early, occurring 1-35 d (median 3 d) post transplantation. Forty
      four episodes were defined as late (> or = 100 d post SCT), occurring 4 months to
      10 years (median 17 months) post transplantation. The incidences of early and
      late IPI were 2.03/1000 and 8.63/1000 transplantations respectively (P = 0.001).
      A higher incidence of late IPI was observed after BMT than after PBSCT (10.99
      versus 3.23/1000; P < 0.01) and after allogeneic versus autologous SCT (12.20
      versus 4.60/1000; P < 0.01). There was a higher estimated incidence of IPI in
      allogeneic patients with than in those without graft-versus-host disease (GVHD)
      (18.85 versus 8.25/1000; P = 0.015). The mortality rate was 20%, including 2/7 of
      early and 8/44 of late IPI. S. pneumoniae is a rare but important complication
      during the aplastic phase after SCT. In conclusion, S. pneumoniae is a
      significant cause of morbidity late post-transplantation, especially in
      allogeneic patients, and particularly those with GVHD. The high IPI mortality
      rate, both early and late post-transplantation, requires preventive approaches,
      mainly effective immunization.

PMID- 11972533
TI  - Economics, health care systems and utilization of haematopoietic stem cell
      transplants in Europe.
AB  - Transplantation of haematopoietic stem cells from blood or bone marrow (HSCT) has
      seen rapid expansion. Increased costs and quality concerns present a challenge
      for health care providers. Information on factors influencing HSCT utilization is
      necessary. Data on 113 827 patients (37 761 allogeneic HSCT and 76 066 autologous
      HSCT), collected from 580 centres in 35 European countries between 1990 and 1999,
      were used. Economic factors, e.g. gross national product per capita, health care
      expenditure per capita and type of health care system were correlated with
      transplant rates (numbers of HSCT per 10 million inhabitants), team density
      (numbers of transplant teams per 10 million inhabitants) and increase in
      transplant numbers for each country. Annual numbers of HSCT increased in all
      European countries from 4234 in 1990 to 18 720 in 1999 irrespective of health
      care system. Economic strength and team density were the main determinants for
      transplant rate. This report reflects changes over the last decade and current
      status of HSCT in Europe. Economic strength, team density and hitherto unknown
      factors influence dissemination of the technology within Europe. These data
      provide a basis for health care planning, regulatory aspects and future research.

PMID- 11972534
TI  - Factor XIII activity levels in patients with allogeneic haematopoietic stem cell
      transplantation and acute graft-versus-host disease of the gut.
AB  - Severe graft-versus-host disease (GvHD) of the gut clinically resembles Crohn's
      disease and ulcerative colitis. As low plasma levels of factor XIII (FXIII) have
      been described in chronic inflammatory bowel disease (CIBD) and as beneficial
      effects of FXIII concentrates in CIBD have been reported, we studied the FXIII
      plasma activity levels in patients undergoing allogeneic stem cell
      transplantation (SCT). In 20 of 22 patients with an uncomplicated course of SCT,
      FXIII stayed within the normal range (median 102 iu/dl, range 74-122), but was
      significantly reduced with the lowest FXIII levels on d 0 and 7 (d 0: median 83
      iu/dl, range 55-165, d 7: median 83, range 70-101). In 20 of 22 patients with
      histologically proven GvHD of the gut, FXIII levels far below the normal range
      were observed (median 50, range 21-87) with a strong correlation between FXIII
      activity levels and degree of GvHD (r = -0.908; P < 0.001). We conclude that
      FXIII is consumed in patients with GvHD of the gut. As FXIII plays a a crucial
      role in haemostasis and wound healing, a study on the potential benefit of FXIII
      substitution in patients with severe GvHD of the gut might be rewarding.

PMID- 11972536
TI  - Prophylactic treatment with fresh-frozen plasma in chronic thrombotic
      thrombocytopenic purpura.

PMID- 11972535
TI  - Cultured autografting for juvenile myelomonocytic leukaemia.
AB  - A case of juvenile myelomonocytic leukaemia (JMML) associated with a chromosomal
      translocation (1;5) is described. Initial cytoreductive therapy failed to control
      the disease. In the absence of a matched family or unrelated donor, a Dexter-type
      long-term bone marrow culture (LTBMC) was established. The LTBMC showed
      preferential growth of normal stem cells over the abnormal clone, allowing a
      cultured autologous stem cell transplantation to be performed. Despite detection
      of the t(1;5) from 5 months to 7 years following cultured autograft, the patient
      remained in haematological remission. Currently the patient is alive and well at
      10 years in full cytogenetic remission.

PMID- 11972537
TI  - Childhood refractory autoimmune haemolytic anaemia: is there a role for anti-CD20
      therapy (rituximab)?

PMID- 11972538
TI  - Treatment of severe fetomaternal alloimmune thrombocytopenia with compatible
      frozen-thawed platelet concentrates.

PMID- 11972540
TI  - Management of intermittent claudication.

PMID- 11972541
TI  - Oncoplastic surgery of the breast.

PMID- 11972542
TI  - Surgical treatment of incisional hernia.
AB  - BACKGROUND: Incisional hernia is a common complication of abdominal surgery and
      an important source of morbidity. It may be repaired using open suture, open mesh
      or laparoscopic mesh techniques. This review examines the results of these
      methods of repair. METHODS: A Medline literature search was performed to identify
      articles relating to 'incisional hernia', 'ventral hernia' and 'wound failure'.
      Relevant papers from the reference lists of these articles were also sought.
      RESULTS: The recurrence rate after open suture repair may be as high as 31-49 per
      cent; for open mesh repair it is between 0 and 10 per cent. Comparative studies
      show that recurrence is significantly more frequent after open suture repair than
      after open mesh repair; complication rates are similar for both procedures.
      Recurrence rates after laparoscopic mesh repair vary from 0 to 9 per cent.
      Comparative studies show that laparoscopic mesh repair is at least as safe and
      effective as open mesh repair. CONCLUSION: Open suture repair for incisional
      hernia carries an unacceptably high recurrence rate. The results of open mesh and
      laparoscopic mesh techniques are encouraging. There is scope for a large
      multicentre randomized clinical trial to compare laparoscopic and open mesh
      repair.

PMID- 11972543
TI  - Pathogenesis of colonic diverticula.
AB  - BACKGROUND: Diverticula are herniations through the colonic wall and are
      therefore likely to be due to a weakness within the wall, an alteration in
      intracolonic pressures or a combination of these factors. This article reviews
      these aspects in relation to the pathogenesis of colonic diverticula. METHODS:
      Medline and Science Citation Index searches were performed to locate English
      language articles relating to the pathogenesis of colonic diverticulosis
      published since 1960. Manual cross-referencing was also performed and some
      historical articles were included. RESULTS AND CONCLUSION: Several theories now
      exist about the development of colonic diverticula. The majority of the evidence
      suggests that the morphological changes are the response to a lifelong
      consumption of a low-residue diet. However, there are complex relations between
      colonic structure, motility and dietary factors, and it is likely that all of
      these (and possibly genetic influences) play a role in the pathogenesis to a
      greater or lesser degree.

PMID- 11972544
TI  - Fracture of the penis.
AB  - BACKGROUND: Sporadic reports of penile fracture give the impression of a rare
      trauma. The value of diagnostic investigations is doubtful and treatment options
      are controversial. METHODS: A Medline search from January 1966 to July 2001 using
      the terms 'fracture of penis', 'penile trauma' and 'coital injuries' was used to
      identify full texts of publications on fracture of the penis. Full texts of
      relevant references from these publications were also identified. Data extracted
      for review included authors, country and year of publication, number of cases in
      each report, aetiology, clinical features, investigations, treatment and outcome.
      RESULTS: In 183 publications 1331 cases were reported between January 1935 and
      July 2001. Most reports were from the Mediterranean region. The commonest causes
      were coitus and penile manipulations, especially masturbation. Most patients were
      in their fourth decade. Clinical features included sudden penile pain,
      detumescence, voiding difficulties, and penile swelling and deviation. Diagnosis
      was made mainly on clinical grounds. Associated injuries included urethral
      rupture. Predisposing factors included excessive force at coitus or manipulation,
      fibrosclerosis of the tunica albuginea and chronic urethritis. Most authors
      advocated early surgical repair using absorbable sutures. Complications of the
      injury included coital difficulty, urethral fistula, penile plaque and erectile
      dysfunction. CONCLUSION: Penile fracture is not rare. Radiological investigations
      are expensive and may delay treatment. Current management favours early surgical
      exploration to prevent complications.

PMID- 11972545
TI  - Levels of the chemokines growth-related oncogene alpha and epithelial neutrophil
      activating protein 78 are raised in patients with severe acute pancreatitis.
AB  - BACKGROUND: Multiple organ dysfunction syndrome secondary to systemic leucocyte
      activation is the major cause of death following an attack of acute pancreatitis.
      Although plasma levels of interleukin (IL) 8 are known to be raised in acute
      pancreatitis, levels of other CXC chemokines such as growth-related oncogene
      (GRO) alpha and epithelial neutrophil-activating protein (ENA) 78, which are also
      potent neutrophil chemoattractants and activators, have not been measured.
      METHODS: Timed plasma samples were obtained from 51 patients with acute
      pancreatitis, 27 with a severe attack and 24 with mild disease according to the
      Atlanta classification. Samples were analysed to determine levels of C-reactive
      protein (CRP), IL-8, GRO-alpha and ENA-78. RESULTS: Plasma levels of IL-8, GRO
      alpha and ENA-78 were increased in patients with severe as opposed to mild acute
      pancreatitis as early as 24 h following disease onset. Using cut-off levels of 7
      pg/ml for IL-8, 70 pg/ml for GRO-alpha and 930 pg/ml for ENA-78, peak levels
      within the first 24 h of admission had an accuracy of 81, 71 and 87 per cent
      respectively in predicting the severity of an attack of acute pancreatitis.
      CONCLUSION: In patients with severe acute pancreatitis plasma levels of GRO-alpha
      and ENA-78 were raised in addition to those of IL-8, suggesting that all three
      chemokines are involved in the inflammatory response in this condition.

PMID- 11972546
TI  - Implications of peritoneal washing cytology in patients with potentially
      resectable pancreatic cancer.
AB  - BACKGROUND: The aim of this study was to assess the implications of positive
      peritoneal washing cytology for management of patients with potentially
      resectable pancreatic cancer. METHODS: Cytological examination of peritoneal
      washings was performed in 134 patients who underwent surgical resection for
      pancreatic adenocarcinoma. The clinicopathological findings and the relationship
      between cytology results (including cytomorphology) and survival were
      investigated. RESULTS: One hundred and fourteen patients (85 per cent) had
      negative cytology results (group 1). Excluding one patient with atypical cells,
      positive cytology results were obtained in 19 patients (14 per cent): 16 patients
      without macroscopic peritoneal metastases (group 2) and three patients with
      minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had
      significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those
      in group 1. However, there were no significant differences in postoperative
      cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in
      group 2 are long-term survivors (40 and 58 months). In cytomorphological
      analyses, the presence of clusters with ragged edges and isolated carcinoma cells
      can be considered to indicate a high risk of peritoneal recurrence. CONCLUSION:
      Positive cytology does not directly predict peritoneal carcinomatosis and, while
      associated with advanced disease, does not contraindicate radical surgery.

PMID- 11972547
TI  - Electrolytic ablation as an adjunct to liver resection: experimental studies of
      predictability and safety.
AB  - BACKGROUND: Combined liver resection and local ablation may offer the only chance
      of cure to patients with liver metastases who are presently deemed unresectable
      because of a single awkwardly placed metastasis. By definition, such a metastasis
      is often close to a major vein. An ablative technique is needed that is both
      predictable and safe in such a circumstance. METHODS: Electrolytic liver lesions
      were created in 21 pigs using platinum electrodes, connected to a direct current
      generator. Both electrolytic 'dose' and electrode separation were varied to
      produce different sized lesions. The 'dose' was correlated with the volume of
      necrosis and any vascular damage was determined histologically. RESULTS: There
      was a significant (P < 0.001) correlation between the electrolytic 'dose' and the
      volume of liver necrosis. For a given 'dose' the volume of necrosis was less when
      the electrodes were together, rather than separated. Liver enzymes were only
      transiently deranged. There were no significant vascular injuries. CONCLUSION:
      Predictable and reproducible necrosis is produced by electrolysis in the pig
      liver. The treatment appears to cause little or no damage to immediately adjacent
      liver or major vascular structures and, when combined with resection, may offer
      the chance of a cure to many patients who are currently unresectable.

PMID- 11972548
TI  - Impact of socioeconomic deprivation on outcome after surgery for colorectal
      cancer.
AB  - BACKGROUND: Previous studies have demonstrated that socioeconomic deprivation is
      associated with poorer survival in patients with colorectal cancer. These
      differences have been attributed to more advanced disease at presentation.
      METHODS: A total of 2269 patients undergoing resection for colorectal cancer in
      hospitals in central Scotland between 1991 and 1994 were studied. Socioeconomic
      status was defined using the Carstairs deprivation index. The impact of
      deprivation on case mix, treatment and outcome was analysed. RESULTS: There were
      no significant differences in mode of presentation, extent of disease at
      presentation, type of resection and postoperative mortality rate among the
      socioeconomic groups. Following curative resection, the overall survival rate at
      5 years was 47.0 per cent in deprived patients, compared with 55.4 per cent in
      affluent patients (P = 0.05); the cancer-specific survival rate was 62.6 per cent
      in the deprived and 68.1 per cent in the affluent (P = 0.05). Compared with the
      affluent, the adjusted hazard ratios for the deprived were 1.36 (95 per cent
      confidence interval (c.i.) 1.09 to 1.69) for overall mortality and 1.26 (95 per
      cent c.i. 0.95 to 1.67) for cancer-specific mortality. Following palliative
      resection, there was no difference in survival between the affluent and deprived
      for either overall (P = 0.27) or cancer-specific (P = 0.89) mortality.
      CONCLUSION: These findings confirm that the cancer-specific survival rate
      following surgery for colorectal cancer is lower in deprived patients. Stage of
      disease at presentation and type of operation did not account for this
      difference. The excess mortality was confined to patients undergoing apparently
      curative resection.

PMID- 11972549
TI  - Prospective study of the incidence and outcome of intra-abdominal hypertension
      and the abdominal compartment syndrome.
AB  - BACKGROUND: Intra-abdominal hypertension has been recognized as a source of
      morbidity and mortality in the traumatized patient following laparotomy. Multiple
      organ dysfunction attributable to intra-abdominal hypertension has been called
      the abdominal compartment syndrome. The epidemiology and characteristics of these
      processes remain poorly defined. METHODS: Intra-abdominal pressure was measured
      prospectively in all patients admitted to a trauma intensive care unit over 9
      months. Data were gathered on all patients with intra-abdominal hypertension.
      RESULTS: Some 706 patients were evaluated. Fifteen (2 per cent) of 706 patients
      had intra-abdominal hypertension. Six of the 15 patients with intra-abdominal
      hypertension had abdominal compartment syndrome. Half of the patients with
      abdominal compartment syndrome died, as did two of the remaining nine patients
      with intra-abdominal hypertension. Patients with abdominal compartment syndrome
      had a mean intra-abdominal pressure of 42 mmHg compared with 26 mmHg in patients
      with intra-abdominal hypertension only (P < 0.05). CONCLUSION: The incidence of
      intra-abdominal hypertension and abdominal compartment syndrome was 2 and 1 per
      cent respectively. Intra-abdominal hypertension did not necessarily lead to
      abdominal compartment syndrome, and often resolved without clinical sequelae.
      Abdominal compartment syndrome did not occur in the absence of earlier
      laparotomy. Abdominal compartment syndrome was associated with a marked increase
      in intra-abdominal pressure (above 40 mmHg).

PMID- 11972550
TI  - Prediction of the response to chemoradiation and prognosis in oesophageal
      squamous cancer.
AB  - BACKGROUND: The sensitivity of cancer cells to chemotherapy and radiation therapy
      depends on various biological properties. This study investigated the expression
      of p53, CDC25B and metallothionein (MT), and evaluated their clinical
      significance in chemoradiation therapy (CRT) for oesophageal squamous cell
      carcinoma. METHODS: The expression of p53, CDC25B and MT was evaluated by
      immunohistochemistry using biopsy specimens taken before CRT for 77 patients with
      oesophageal squamous cell carcinoma, and correlated with the pathological effects
      of CRT and survival. RESULTS: p53-positive tumours and MT-positive tumours had a
      poor response to CRT, whereas tumours with strong CDC25B expression were
      associated with a good response. When each patient was scored for the presence of
      the three biological factors, there was a strong correlation between the
      sensitivity score and the pathological effect of CRT (P < 0.001), and a (non
      significant) difference in the 5-year survival rate between patients with a high
      score and those with a low score (67 versus 34 per cent respectively; P = 0.12).
      CONCLUSION: The combined evaluation of p53, CDC25B and MT may help to identify
      patients with advanced oesophageal squamous cell carcinoma who will benefit from
      preoperative CRT.

PMID- 11972551
TI  - Radio-guided sentinel node detection for gastric cancer.
AB  - BACKGROUND: Radio-guided detection of sentinel nodes (SNs) has been used to
      predict regional metastases in patients with malignant melanoma and breast
      cancer. However, the validity of the SN hypothesis is still controversial for
      gastrointestinal cancers including gastric cancer. The aim of this study was to
      test the feasibility and accuracy of radio-guided mapping of SNs for gastric
      cancer. METHODS: Some 145 consecutive patients with gastric cancer diagnosed as
      T1 or T2 and evaluated clinically as N0 were enrolled. Endoscopic injection of
      technetium-99m-radiolabelled tin colloid was performed before operation and
      radioactive SNs were identified with a gamma probe. Standard radical gastrectomy
      with lymphadenectomy was performed in all patients and all resected nodes were
      evaluated by routine histopathological examination. RESULTS: Using radio-guided
      methods, SNs were detected in 138 (95.2 per cent) of 145 patients. The SN was
      positive in 22 of 24 patients with lymph node metastasis. The incidence of
      metastasis in the SNs (7.8 per cent) was significantly higher than that in the
      non-SNs (0.3 per cent) (P < 0.01). The diagnostic accuracy according to SN status
      was 98.6 per cent (136 of 138). CONCLUSION: Radio-guided SN mapping is an
      accurate diagnostic procedure for detecting lymph node metastasis in patients
      with early-stage gastric cancer.

PMID- 11972552
TI  - Extended preservation of non-heart-beating donor livers with normothermic machine
      perfusion.
AB  - BACKGROUND: Non-heart-beating donor (NHBD) livers represent an important organ
      pool, but are seldom utilized clinically and require rapid retrieval and
      implantation. Experimental work with oxygenated perfusion during preservation has
      shown promising results by recovering function in these livers. This study
      compared sanguinous perfusion with cold storage for extended preservation of the
      NHBD liver in a porcine model. METHODS: Porcine livers were subjected to 60 min
      of in vivo total warm ischaemia before flushing, after which they were preserved
      by one of two methods: group 1 (n = 4), University of Wisconsin (UW) solution by
      standard cold storage for 24 h; group 2 (n = 4), oxygenated autologous blood
      perfusion on an extracorporeal circuit for 24 h. All livers were subsequently
      tested on the circuit during a 24-h reperfusion phase. RESULTS: Livers in group 1
      showed no evidence of viability during the reperfusion phase with no bile
      production or glucose utilization; they also displayed massive necrosis. Livers
      in group 2 demonstrated recovery of function by synthetic function, substrate
      utilization and perfusion haemodynamics; these livers displayed less cellular
      injury by hepatocellular enzymes. All differences in parameters between the two
      groups were statistically significant (P < 0.05). These findings were supported
      by histological examination. CONCLUSION: Warm ischaemia for 1 h and simple cold
      storage (UW solution) for 24 h renders the liver non-viable. Oxygenated,
      sanguinous perfusion as a method of preservation recovers liver function to a
      viable level after 24 h of preservation.

PMID- 11972553
TI  - Experimental study of peritoneal blood flow and insufflation pressure during
      laparoscopy.
AB  - BACKGROUND: Port-site metastases after laparoscopic surgery may occur with
      greater frequency than would be expected following open resection of intra
      abdominal malignancies, but the causal mechanism for this is incompletely
      understood. The possibility that insufflation may increase peritoneal blood flow
      producing a wound environment conducive to the formation of metastases was
      investigated. METHODS: The effects of insufflation gas type and pressure were
      studied in 30-kg female pigs. Pigs were divided into five groups, which were
      subjected to insufflation at 12 mmHg pressure with helium, insufflation at 12, 8
      or 4 mmHg pressure with carbon dioxide, or laparotomy. A microsphere technique
      utilizing two distinct radiotracers, 99mTc-labelled macroaggregated albumin (MAA)
      and 51Cr-labelled MAA, was used to study blood flow to the peritoneum, liver and
      kidneys. RESULTS: Insufflation with carbon dioxide or helium gases had no effect
      on renal (P < 0.09) or hepatic blood flow (P = 0.54). However, insufflation
      significantly increased peritoneal blood flow when carbon dioxide (P < 0.05), but
      not when helium (P = 0.99), was used as the insufflating gas. CONCLUSION: These
      data suggest that blood flow within the peritoneum is influenced by insufflation
      with carbon dioxide. It is conceivable that such hyperaemia could increase the
      propensity for implanted tumour cells to metastasize in these sites following
      laparoscopy.

PMID- 11972564
TI  - Improving communication: a constant challenge.

PMID- 11972565
TI  - Management of squamous cell carcinoma of the anus.

PMID- 11972566
TI  - Exploring loss to follow-up: abnormal Pap screening in Hispanic patients.
AB  - PURPOSE: The loss of patients to follow-up for abnormal findings from Pap
      screenings is an important public health concern, particularly among poor and
      minority women. This study explores factors affecting incomplete follow-up among
      a group of Hispanic women with low incomes. DESCRIPTION OF STUDY: A qualitative
      descriptive study was conducted of 11 Hispanic patients with incomplete Pap smear
      follow-up at a public clinic in a major city in south Texas. Patients were
      interviewed using a semistructured, open-ended schedule of questions, and their
      medical records were abstracted. The clinic's five staff members also were
      interviewed. Comparative chronologies were constructed for each case, contrasting
      patient and staff accounts of the same set of events. All data were coded by at
      least two investigators. RESULTS: All study patients had mildly abnormal Pap
      smear results and had not met the follow-up criteria, but all understood and were
      committed to Pap screening. Although viewed by staff as noncompliant, none of the
      patients viewed her behavior this way. This staff-patient discrepancy was
      attributable to poor communication, mixed messages, clinic errors, and, perhaps
      most importantly, to a conflict between program policies and the specific
      circumstances of individual cases. Two case examples are presented to illustrate
      key points. CLINICAL IMPLICATIONS: Strategies that may help to reduce loss to
      follow-up among similar patients include the following: allowing clinic staff
      more flexibility in follow-up procedures for women who have consistently normal
      follow-up tests, including Spanish translations of written messages; enlisting
      patients' agreement in setting appointments; and updating patient records to
      reflect follow-up care that had been received in other clinics.

PMID- 11972567
TI  - Abnormal mammogram follow-up: a pilot study women with low income.
AB  - PURPOSE: The purpose of this study was to test an intervention (the Screening
      Adherence Follow-up Program [SAFe]) that was designed to reduce the number of
      known barriers to diagnostic follow-up adherence and initiation of treatment
      among women with low incomes who had abnormal mammogram findings. DESCRIPTION OF
      PROGRAM: The investigators developed and implemented a highly structured, theory-
      and evidence-based intervention that combined health education, counseling, and
      systems navigation, which was delivered by a team consisting of a peer counselor
      and a social worker who held a masters degree. A scripted baseline telephone
      interview identified potential barriers to follow-up adherence and provided
      counseling interventions for each patient. Patients were assigned to different
      service intensities based on the level of risk for nonadherence. Patients with
      significant mental health symptoms, psychosocial stressors, or who had received a
      diagnosis of cancer were referred to the team social worker for further
      assessment and intervention. Patients also received reinforcing telephone follow
      up calls at 6 and 12 months. RESULTS: An observational pilot study of SAFe (N =
      605) in two large urban diagnostic centers showed that 71% of women receiving
      SAFe were Hispanic, 18% were Black, and 11% were from other ethnic backgrounds.
      Adherence rates through diagnostic resolution and the initiation of treatment for
      women who had received a diagnosis of cancer were 93% and 90%, respectively, at
      the two study sites. Rates of adherence among women who could not be located or
      who refused study consent were significantly lower (72% and 69%, respectively).
      The rate of timely adherence was also higher among the women served. Patient
      satisfaction with SAFe was generally high. CLINICAL IMPLICATIONS: Study results
      support the combining of interventions and the practical utility of a clinical
      decision-making algorithm to determine individualized nonadherence risk and to
      assign service intensity based on individual need. Problems in locating women for
      enrollment were experienced.

PMID- 11972568
TI  - Promoting fecal occult blood testing in rural African American women.
AB  - PURPOSE: The purpose of this experimental study was to test the effectiveness of
      a multiphasic culturally relevant intervention, delivered over a 1-year period to
      increase the rates of participation in fecal occult blood testing (FOBT) at the
      initial screening opportunity and at the 1-year follow-up screening opportunity
      among rural African American women. DESCRIPTION OF STUDY: The study used a
      pretest/post-test design among African American women who attended senior citizen
      centers in a rural southern state. The centers were randomly assigned to the
      cultural and self-empowerment group, who received the five-phased intervention,
      the modified cultural group, who received phase I of the intervention only, or
      the traditional group, who served as the control group. Data were collected at
      the initial and 1-year follow-up screenings. Hemoccult kits were distributed,
      collected, and analyzed at no cost to the participants. Data were analyzed using
      descriptive statistics, repeated measures, and longitudinal models for binary
      outcomes. RESULTS: Women in the cultural and self-empowerment group had a
      significantly higher rate of participation in FOBT than did those in the modified
      cultural group and the traditional group. The modified cultural group had a
      significantly higher rate of participation in FOBT than the did the traditional
      group. Predictors of participation in FOBT were the women's family history of
      colorectal cancer and the average number of visits to their healthcare provider.
      CLINICAL IMPLICATIONS: Colorectal cancer screening and diagnostic testing
      opportunities should be offered consistently to women who visit their provider
      for routine, nonemergent office visits. As successful interventions to increase
      colorectal cancer screening are introduced into community settings, these
      interventions also should be tested within physicians' offices and other
      community agencies.

PMID- 11972569
TI  - Telephone-linked care for cancer symptom monitoring: a pilot study.
AB  - PURPOSE: The purpose of this pilot project was to explore the feasibility of
      using a telephone-based computerized system to monitor postchemotherapy symptoms
      and to test the mechanism of generating alert communications to healthcare
      providers about symptoms that are poorly controlled. DESCRIPTION OF STUDY: Twenty
      seven patients with cancer participated in the study by calling the telephone
      linked care (TLC) system daily during a single cycle of chemotherapy and
      reporting on seven common chemotherapy-related symptoms. Using selected symptom
      data, symptoms that met a preset threshold for severity generated a fax
      notification of the patient's symptom pattern to the physician. Patients then
      were interviewed about their satisfaction with TLC and about suggestions for
      improvement. RESULTS: The study demonstrated that TLC is easy to learn and use
      and that it captures daily symptom information from patients in their homes. A
      majority of patients experienced symptoms that were severe enough to generate
      symptom-alert faxes. Patient satisfaction with TLC was high. The technique, TLC
      voice, and the duration of the calls were acceptable to patients. There were few
      technical problems. CLINICAL IMPLICATIONS: The TLC system has the potential to
      improve dramatically symptom monitoring and symptom care of patients with cancer
      at home. Further testing is needed, but the TLC chemotherapy monitoring
      application shows promise for improving supportive-care service delivery for
      cancer patients. In its initial test, the TLC chemotherapy monitoring application
      has been shown to be highly acceptable to patients, able to generate useful
      symptom data, and able to generate faxed alerts to healthcare providers, thus
      improving communication about poorly controlled symptoms.

PMID- 11972570
TI  - Online cancer patient education: evaluating usability and content.
AB  - PURPOSE: Two patient education CD-ROMs were converted to a web-based environment.
      This article reports on users' evaluations of the programs' usability and
      content. DESCRIPTION OF EVALUATION: Subscribers to a center's web newsletter were
      asked to view one of two web programs and to complete a survey. The first 150
      respondents were offered a free patient education CD-ROM of their choice, but
      users continued to respond to the survey even after a notice stated that 150
      responses were received. A total of 301 surveys were completed (Colorectal Cancer
      Program 168; Chemotherapy Program 133). RESULTS: Sixty-eight percent of
      Colorectal Cancer Program respondents and 50% of Chemotherapy Program respondents
      considered the program to be more useful or much more useful than any other
      source of information on the topic. A majority of users for both programs
      preferred to view the information on the Internet rather than on CD-ROM. Many
      users reported trouble accessing certain segments of the media. Common complaints
      included the inability to open video or audio clips and the length of time needed
      for each page to load, despite a high-speed Internet connection. CLINICAL
      IMPLICATIONS: Internet use is high, with 60% of US households reporting having
      used the Internet to search for health information. However, little is known
      about user satisfaction with specific sites and what about them users like or do
      not like. It is hoped that these and other user evaluations will help web site
      authors and developers improve their sites.

PMID- 11972571
TI  - Complementary and alternative therapies in cancer symptom management.

PMID- 11972572
TI  - Using international web sites as a cancer resource.

PMID- 11972573
TI  - Mini-allogeneic stem cell transplantation.

PMID- 11972575
TI  - Age at onset and sex ratio in cluster headache: observations over three decades.
AB  - Five hundred and fifty-four patients with episodic cluster headache (ECH) and
      chronic cluster headache (CCH) were examined between 1963 and 1997. Mean age at
      onset was significantly higher in women with CCH compared with women with ECH and
      in men with ECH or CCH. In women with CCH age at onset was evenly distributed
      from 10 to 69 years, whereas in men with CCH and in both sexes with ECH, there
      was a peak when they were in their 20s. In women with ECH a second peak of onset
      occurred in their 50s. Although not statistically significant, primary CCH
      started later in women (mean 50.8 years) than secondary CCH (mean 35.5 years).
      There was a significant variation in the male : female ratio with respect to age
      at onset, being largest between 30 and 49 years of age (ECH 7.2 : 1; CCH 11.0 :
      1) and lowest after 50 (ECH 2.3 : 1; CCH 0.6 : 1). During the observation period
      of more than 30 years there was a trend towards a decreasing male preponderance;
      the male : female ratio was significantly higher among patients with onset before
      rather than after 1970. The proportion of episodic vs. chronic CH did not change
      during the study period. The nature of the sex- and age-related pattern of
      cluster headache onset remains to be elucidated but mechanisms associated with
      sex hormone regulation, perhaps of hypothalamic origin, may be involved, as well
      as environmental factors related to lifestyle.

PMID- 11972574
TI  - Characterization of sumatriptan-induced contractions in human isolated blood
      vessels using selective 5-HT(1B) and 5-HT(1D) receptor antagonists and in situ
      hybridization.
AB  - The 5-HT(1B/1D) receptor agonist sumatriptan is effective in aborting acute
      attacks of migraine and is known to cause constriction of cranial arteries as
      well as some peripheral blood vessels. The present study set out to investigate
      whether 5-HT(1B) and/or 5-HT(1D) receptors mediate contractions of the human
      isolated middle meningeal and temporal arteries (models for anti-migraine
      efficacy) and coronary artery and saphenous vein (models for side-effect
      potential). Concentration-response curves were made with sumatriptan (1 nm-100
      microm) in blood vessels in the absence or presence of selective antagonists at 5
      HT(1B) (SB224289) and 5-HT(1D) (BRL15572) receptors. SB224289 antagonized
      sumatriptan-induced contractions in all blood vessels, although the antagonism
      profile was different amongst these blood vessels. In the temporal artery,
      SB224289 abolished contraction to sumatriptan, whereas in the middle meningeal
      artery and saphenous vein sumatriptan-induced contractions were blocked in an
      insurmountable fashion. Moreover, SB224289 acted as a weak surmountable
      antagonist in the coronary artery (pK(B): 6.4 +/- 0.2). In contrast, BRL15572 had
      little or no effect on sumatriptan-induced contractions in the four blood vessels
      investigated. In situ hybridization revealed the expression of 5-HT(1B) receptor
      mRNA in the smooth muscle as well as endothelial cells of the blood vessels,
      whereas the mRNA for the 5-HT(1D) receptor was only very weakly expressed. These
      results show that the 5-HT(1B) receptor is primarily involved in sumatriptan
      induced contractions of human cranial as well as peripheral blood vessels.

PMID- 11972576
TI  - Zolmitriptan orally disintegrating tablet is effective in the acute treatment of
      migraine.
AB  - A new formulation of zolmitriptan has been developed that dissolves on the tongue
      without the need for additional fluid intake. In this double-blind, parallel
      study, 471 patients were randomized to receive the zolmitriptan orally
      disintegrating tablet 2.5 mg (n=231) or matching placebo (n=240) to treat a
      single moderate or severe migraine. Headache relief following zolmitriptan 2.5 mg
      (63%) was significantly greater than with placebo (22%) at 2 h post-dose (primary
      endpoint; P < 0.0001). The zolmitriptan orally disintegrating tablet was also
      significantly more effective than placebo for 1-, 2- and 4-h pain-free response
      (8% vs. 3%, P=0.0207, 27% vs. 7%, P < 0.0001, and 37% vs. 11%, P < 0.0001,
      respectively). Of those patients stating a preference, 70% of patients preferred
      the orally disintegrating tablet to a conventional tablet. Zolmitriptan orally
      disintegrating tablets are an effective and convenient alternative to a
      conventional tablet, allowing migraine attacks to be treated anytime a migraine
      strikes, which can facilitate earlier treatment.

PMID- 11972577
TI  - Neurovascular headache and a midbrain vascular malformation: evidence for a role
      of the brainstem in chronic migraine.
AB  - Migraine is a common, disabling form of primary headache that has been linked by
      functional imaging studies to activation in the rostral brainstem. In specialty
      clinics migraine is most commonly seen in association with frequent less feature
      full headache that has been called transformed migraine or more recently termed
      chronic migraine. A patient is described with frequent migraine, 3 days per week,
      and less feature full headaches on other days. The patient has a cavernoma in the
      midbrain that has bled. She was previously headache free and now has
      contralateral daily headache. The patient supports the functional imaging
      observations from positron emission tomography (PET) that the rostral brainstem
      is pivotal in migraine pathophysiology, particularly the contralateral midbrain
      periaqueductal grey matter. Moreover, the patient's lesion provides biologically
      plausible support that a single entity causes her clinical presentation: chronic
      migraine, not two-disorders, migraine and tension-type headache.

PMID- 11972578
TI  - Neuropeptide expression in the human trigeminal nucleus caudalis and in the
      cervical spinal cord C1 and C2.
AB  - In migraine and other primary headaches there is a strong vascular component.
      Besides the trigeminovascular components some of the associated symptoms point to
      the involvement of brain stem regions. The central limb of the trigeminal
      vascular pathway is its projection to the trigeminal nucleus caudalis (TNC) and
      to the C1-C2 levels of the spinal cord. The aim of the present study was to
      demonstrate the occurrence of some neurotransmitters in these regions in man. In
      both the TNC and in the Rexed's laminae I and II of the dorsal horns at the C1
      and C2 levels there were numerous substance P immunoreactive fibres. Fibres
      containing calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase
      activating peptide (PACAP) were moderately dense in number. Fibres containing
      vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS) were not seen
      in the TNC or at the C1 and C2 levels of the spinal cord.

PMID- 11972579
TI  - Motion sickness and migraine: optokinetic stimulation increases scalp tenderness,
      pain sensitivity in the fingers and photophobia.
AB  - The aim of this study was to determine whether scalp tenderness and photophobia,
      two well-recognized symptoms of migraine, develop during the motion sickness
      induced by optokinetic stimulation. To investigate whether motion sickness has a
      general influence on pain perception, pain was also assessed in the fingertips.
      After optokinetic stimulation, nausea increased more and headache persisted
      longer in 21 migraine sufferers than in 15 non-headache controls. Scalp
      tenderness increased during optokinetic stimulation in nauseated subjects, and
      pain in the fingertips increased more and photophobia persisted longer in
      migraine sufferers than controls. These findings suggest that the disturbance
      responsible for nausea also sensitizes trigeminal nociceptive neurones or
      releases inhibitory controls on their discharge. A low nausea threshold and a
      propensity for sensitization to develop rapidly in nociceptive pathways may
      increase susceptibility to migraine.

PMID- 11972580
TI  - The movement-related potential in children with migraine and tension-type
      headache.
AB  - Migraine is characterized by an elevated contingent negative variation (CNV) in
      adults and children. In the present study the movement-related potential
      preceding self-initiated movements, the Bereitschaftspotential, was investigated
      in 30 children (mean age 12 years) who were suffering from migraine and tension
      type headache and in 16 healthy age-matched controls. Children pressed a button
      80 times with the right index finger while movement-related potentials were
      recorded from frontal and central electrodes. Whereas healthy children evidenced
      positive movement-related potentials at left and midline positions, children with
      migraine and tension-type headache showed negative movement-related potentials at
      midline leads without lateralization. Negativity was even more pronounced in
      cases of migraine with than without aura symptoms.

PMID- 11972581
TI  - Lack of age-dependent development of the contingent negative variation (CNV) in
      migraine children?
AB  - Increased negativity of contingent negative variation (CNV) in adult migraineurs
      is thought to reflect cortical hyperexcitability. CNV amplitude changes with age
      in healthy adults. Recently, evidence emerged that this might not be the case for
      migraineurs. Our study investigates age-dependency of CNV during childhood age.
      Seventy-six healthy controls and 61 children with migraine without aura (IHS code
      1.1) between 6 and 18 years were examined using an acoustic S1-S2-CNV-paradigm
      with a 3-s inter-stimulus interval. The amplitude of the late component of CNV,
      as well as total CNV at the vertex (Cz according to the international 10-20
      system), were significantly higher in migraineurs without aura than in controls.
      Healthy controls showed increasing amplitudes of CNV with age, whereas in
      migraine children without aura amplitudes did not change. Thus group differences
      were reduced during adolescence. Increased CNV negativity might reflect a
      biological vulnerability to migraine, rather than being a result of
      chronification. Migraineurs seem to lack age-dependent development of CNV also
      during early age, which supports the hypothesis of migraine as a maturation
      disorder.

PMID- 11972582
TI  - Open label trial of coenzyme Q10 as a migraine preventive.
AB  - The objective was to assess the efficacy of coenzyme Q10 as a preventive
      treatment for migraine headaches. Thirty-two patients (26 women, 6 men) with a
      history of episodic migraine with or without aura were treated with coenzyme Q10
      at a dose of 150 mg per day. Thirty-one of 32 patients completed the study; 61.3%
      of patients had a greater than 50% reduction in number of days with migraine
      headache. The average number of days with migraine during the baseline period was
      7.34 and this decreased to 2.95 after 3 months of therapy, which was a
      statistically significant response (P < 0.0001). Mean reduction in migraine
      frequency after 1 month of treatment was 13.1% and this increased to 55.3% by the
      end of 3 months. Mean migraine attack frequency was 4.85 during the baseline
      period and this decreased to 2.81 attacks by the end of the study period, which
      was a statistically significant response (P < 0.001). There were no side-effects
      noted with coenzyme Q10. From this open label investigation coenzyme Q10 appears
      to be a good migraine preventive. Placebo-controlled trials are now necessary to
      determine the true efficacy of coenzyme Q10 in migraine prevention.

PMID- 11972583
TI  - Spatial contrast sensitivity of migraine patients without aura.
AB  - Visual disturbances are frequent symptoms in migraine. Since there is a
      possibility of separate damage in the magno- or parvo-cellular visual pathway in
      migraine patients, we performed a study including the measurement of static and
      dynamic spatial contrast sensitivity on 15 patients suffering from migraine
      without aura under photopic and scotopic conditions. Fifteen healthy volunteers
      without primary headache served as controls. The results revealed a marked
      decrease in contrast sensitivity at low spatial frequencies in the migraine
      patients. Spatial contrast sensitivity demonstrated some lateralization, as the
      sensitivity to low spatial frequencies obtained through separate eyes showed
      significantly larger side-differences in migraine patients than in control
      subjects. These findings suggest that the mechanisms responsible for vision at
      low spatial frequencies are impaired in migraine patients. This might indicate
      impaired function of the magnocellular pathways in this condition.

PMID- 11972584
TI  - Is there any relationship between handedness and unilateral headache in migraine?

PMID- 11972585
TI  - Resolution of migraine with aura after successful treatment of a pituitary
      microadenoma.

PMID- 11972586
TI  - Selective damage of trigeminal Adelta fibres in Raeder's syndrome following
      dissection of the ICA detected by a nociceptive blink reflex.

PMID- 11972587
TI  - Symptomatic migraine linked to stroke due to paradoxical embolism and elevated
      thrombosis risk.

PMID- 11972588
TI  - Hypnic headache: rapid and long-lasting response to prednisone in two new cases.

PMID- 11972589
TI  - Age of onset in cluster headache: the clinical spectrum (three case reports).

PMID- 11972590
TI  - Allergen avoidance: the attraction of charge.

PMID- 11972591
TI  - Oxidative stress and adaptive response of glutathione in bronchial epithelial
      cells.

PMID- 11972592
TI  - H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac
      effects.
AB  - This review addresses novel concepts of histamine H1-receptor function and
      attempts to relate them to the anti-inflammatory effects of H1-antihistamines.
      Furthermore, the molecular mechanisms underlying the cardiotoxic effects of H1
      antihistamines are discussed. H1-receptors are G-protein-coupled-receptors
      (GPCRs), the inactive and active conformations of which coexist in equilibrium.
      The degree receptor activation in the absence of histamine is its 'constitutive
      activity'. In this two-state model, histamine acts as an agonist by combining
      with and stabilizing the activated conformation of the H1-receptor to shift the
      equilibrium towards the activated state. Drugs classified previously as
      antagonists act as either inverse agonists or neutral antagonists. Inverse
      agonists combine with and stabilize the inactive conformation of the receptor to
      shift the equilibrium towards the inactive state. Thus, they may down-regulate
      constitutive receptor activity, even in the absence of histamine. Neutral
      antagonists combine equally with both conformations of the receptor, do not
      affect basal receptor activity but do interfere with agonist binding. All H1
      antihistamines examined to date are inverse agonists. As the term 'H1-receptor
      antagonists' is obviously erroneous, we suggest that it be replaced by 'H1
      antihistamines'. The observations that H1-receptors modulate NF-kappaB activation
      and that there are complex interactions between GPCRs, has allowed us to
      postulate receptor dependent-mechanisms for some anti-inflammatory effects of H1
      antihistamines, e.g. inhibition of ICAM-1 expression and the effects of
      bradykinin. Finally, the finding that blockade of HERG1 K+ channels is the
      mechanism by which some H1-antihistamines may cause cardiac arrhythmias has
      allowed the development of preclinical tests to predict such activity.

PMID- 11972593
TI  - Where next in basic asthma research?

PMID- 11972594
TI  - Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a
      randomized controlled trial.
AB  - BACKGROUND: Previous studies suggest that sublingual immunotherapy (SLIT)
      represents a safer alternative to injection immunotherapy but equivalent efficacy
      is yet to be confirmed. OBJECTIVE: To evaluate the efficacy and safety of SLIT in
      grass pollen-induced seasonal rhinoconjunctivitis. METHODS: A randomized, placebo
      controlled trial in 56 adults over 18 months. Outcome measures included diary
      scores of seasonal symptoms and medication use, overall assessments, conjunctival
      and intradermal provocation tests and serum antibody measurements. To investigate
      possible mechanisms, sublingual biopsies were taken for measurement of local T
      cells, antigen-presenting cells and IL-12 mRNA expression. RESULTS: There were no
      significant differences between the immunotherapy (IT) and placebo groups for
      diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients'
      overall assessment of hayfever severity compared with previous years showed a
      highly significant improvement in favour of the IT group (P < 0.02). After
      treatment the late skin response was smaller (P = 0.003) and the ratio of serum
      allergen-specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these
      variables correlated with the clinical response to SLIT. There were no
      differences between groups in either the sublingual epithelium or lamina propria
      for numbers of CD3+ cells (epithelium: P = 0.9, lamina propria: P = 0.2), CD1a+
      cells (P = 0.3, P = 0.25), CD68+ cells (P = 0.9, P = 1.0) or IL-12 mRNA+ cells (P
      = 0.6, P = 0.4). Local side-effects were minor and there were no serious
      treatment-related adverse events. CONCLUSION: Grass pollen sublingual
      immunotherapy was well tolerated. Although there was no significant change in
      diary scores, the improvement in overall assessments, which correlated with
      inhibition of the late skin response and increases in serum IgG4 : IgE ratio,
      indicates the need for larger, dose-ranging studies.

PMID- 11972596
TI  - Prevalence and predictors of atopy among young Danish adults.
AB  - BACKGROUND: The prevalence of atopic diseases is increasing in western countries,
      and environmental exposures in childhood may influence development of atopic
      sensitization. OBJECTIVE: To investigate the prevalence and predictors of atopy
      among young Danish adults. METHODS: Of 940 invited subjects, aged 19-29 years,
      complete data were obtained from 525 (56%) subjects. All completed a
      questionnaire concerning asthma, rhinitis, preschool nursery care, smoking
      habits, family size, education and employment. A skin prick test was performed,
      and pulmonary function was measured using standard techniques. Atopy was defined
      as a positive skin prick test. RESULTS: The frequency of atopy was 32% (males 43%
      vs. females 23%, P < 0.001). We found a positive association between atopy and
      atopic dermatitis (P < 0.05), rhinitis (P < 0.001), itching when eating nuts (P <
      0.001) and current asthma (P < 0.001). There was an inverse relation between
      atopy and having furred pets in childhood (P < 0.05), passive smoking in
      childhood (P < 0.01) and current passive smoking (P < 0.05). An increasing number
      of siblings was inversely related to atopy to grass (P < 0.05); however, only an
      increasing number of older siblings seemed to protect from atopy to grass (P <
      0.05). Subjects who had never attended a day-care centre had significantly more
      atopy to grass (P < 0.05). No significant association was found between atopy and
      airway infections requiring hospitalization before the age of 5 years, or between
      atopy and bedroom sharing in childhood. CONCLUSION: Atopy is common among young
      Danish adults, especially in males. Participants were less likely to be atopic,
      especially to grass allergen, if they came from large families, had kept furred
      pets as children, and had been exposed to tobacco smoke.

PMID- 11972595
TI  - The effect of corona discharge on Der p 1.
AB  - BACKGROUND: Reduction of house dust mite allergens in the domestic environment
      can play an important part in reducing sensitization and in the amelioration of
      symptoms in atopic individuals. Chemical and physical methods have been tried
      with varied levels of success. The present paper presents a novel electrostatic
      way of destroying Der p 1, the major mite allergen. OBJECTIVE: To assess the
      efficacy of negative Trichel, negative continuous glow, positive pulse and
      positive continuous glow corona in destroying Der p 1. To determine whether ozone
      has any effect on the integrity of Der p 1 in the experimental conditions
      present. METHODS: A simple point-to-plane apparatus was used to irradiate samples
      of Der p 1 for periods of 1, 15, 30, 45, 60, 120, 180, 240 and 300 min. Controls
      were exposed to the atmosphere with no corona products present for the equivalent
      time. The effect of the corona by-product ozone was investigated alone by
      exposing samples of Der p 1 to molecular ozone for 60 min. Der p 1 concentration
      was quantified by two-site monoclonal antibody ELISA. RESULTS: High current
      negative glow resulted in a 67.37% reduction in Der p 1 concentration after 300
      min compared with a 50.5% reduction from a low current Trichel regime. High
      current positive glow corona gave a reduction of 25.22% while a low current
      positive pulse corona caused a 13.72% reduction after 300 min. All these
      reductions were statistically significant (P < 0.05) compared with unexposed
      controls. Negative corona always gave greater percentage reductions in Der p 1
      concentration for each time exposure investigated. The pattern of percentage
      reduction follows an exponential rise to maximum relationship in respect to time.
      Samples of Der p 1 were not affected by exposure to molecular ozone. CONCLUSION:
      These data indicate corona products to be a powerful new method of destroying Der
      p 1 allergen that is not dependent on the presence of the oxidizing corona
      product ozone.

PMID- 11972597
TI  - Cultural adaptation is associated with atopy and wheezing among children of
      Turkish origin living in Germany.
AB  - BACKGROUND: Turkish children have been found to suffer less from atopic diseases
      than their German peers. The underlying causes are unknown. OBJECTIVE: To
      evaluate rates of sensitization and atopic disease among children in Germany with
      German or Turkish ethnicity and different degrees of cultural adaptation.
      METHODS: This was a cross-sectional study. The setting was screening for school
      eligibility in an inner-city district of Berlin/Germany. The participants were
      preschool children born in Germany with double German or double Turkish parental
      citizenship. Cultural adaptation of Turkish children was assessed by the language
      parents used to communicate with their child: only Turkish (n = 60, group A);
      Turkish and German (n = 269, group B); and only German (n = 103, group C). Group
      D contained children from German parents (n = 383). The main outcome measures
      were specific sensitization to common aeroallergens (CAP-System, Pharmacia
      Phadiatop >or= 0.35 kU/L), and lifetime and 1-year prevalences of allergic
      disease symptoms (ISAAC questionnaire in German and Turkish, Mantel-Haenszel test
      for trend). RESULTS: Sensitization rates for groups A, B, C and D were 8.0%,
      6.8%, 18.9% and 18.3%, respectively (P = 0.004). The corresponding prevalence
      rates for wheeze ever were 6.7%, 9.3%, 12.6% and 21.3% (P < 0.001), wheeze in the
      past year 3.3%, 3.7%, 9.7% and 10.2% (P = 0.001), itchy rash ever 3.3%, 6.3%,
      8.7% and 13.7% (P < 0.001), itchy rash in the past year 1.7%, 3.7%, 4.9% and 9.5%
      (P < 0.001), respectively. No significant differences were found for hay fever
      symptoms. CONCLUSIONS: Higher cultural adaptation is correlated with higher rates
      of allergic sensitization and disease among children of Turkish origin living in
      Berlin. This correlation suggests that environmental rather than genetic
      differences are responsible for the differences observed.

PMID- 11972598
TI  - Atopy may be related to exercise-induced bronchospasm in asthma.
AB  - BACKGROUND: Recent studies suggest that atopy may be associated with exercise
      induced bronchospasm (EIB) in asthma. However, it is not clear whether atopy is
      related to EIB, regardless of airway hyper-responsiveness (AHR) to methacholine,
      because asthmatic subjects often show AHR to exercise and methacholine
      simultaneously. OBJECTIVE: To investigate whether atopy is related to EIB in
      asthmatic subjects, independently of AHR to methacholine. METHODS: Fifty-eight
      male asthmatic subjects were studied. Initial spirometry was performed. Skin
      prick test was carried out, using 53 common allergens including mites dust
      antigen. Atopy score was defined as a sum of mean weal diameters to all allergens
      tested. Methacholine bronchial provocation testing was performed. Twenty-four
      hours later, free running test was performed. Positive EIB was defined as a 15%
      reduction or more in FEV1 from baseline after exercise. RESULTS: All subjects had
      AHR to methacholine. The degree of AHR to methacholine in asthmatics with EIB was
      similar to that in asthmatics without EIB. However, atopy score and skin reaction
      to Dermatophagoides pteronyssinus significantly increased in asthmatics with EIB
      compared with those without EIB (P < 0.05, respectively). Furthermore, the degree
      of EIB significantly correlated with atopy score in all subjects (r = 0.35, P <
      0.01). This relationship was maintained even after the exclusion of EIB-negative
      asthmatic subjects. CONCLUSION: Atopy defined as skin test reactivity may
      contribute to the development of EIB in asthma, independently of AHR to
      methacholine.

PMID- 11972599
TI  - Rhinovirus-induced alterations on peripheral blood mononuclear cell phenotype and
      costimulatory molecule expression in normal and atopic asthmatic subjects.
AB  - BACKGROUND: Rhinovirus (RV) infection is the commonest trigger of acute asthma
      exacerbations; however, the immune response to these viruses and any potential
      implications in the mechanisms leading to asthma exacerbations are not well
      understood. OBJECTIVE: To assess the effects of in vitro RV infection on the
      phenotype and expression of costimulatory molecules on peripheral blood
      mononuclear cells (PBMC) from normal and atopic asthmatic subjects, as a model
      for RV antigen presentation. METHODS: PBMC from seven normal and seven asthmatic
      subjects were exposed to one infectious unit/cell of RV16 for 48 h. Surface
      expression of CD25, CD28, CD40, CD54, CD80, CD86 and CTLA-4 was evaluated on CD3,
      CD4, CD8, CD14 and CD19 PBMC subpopulations by three-colour flow cytometry.
      RESULTS: No changes in the percentage of CD3, CD4, CD8 or CD19 were observed.
      CD14 was significantly reduced by the infection and this was more pronounced in
      normal subjects. On Th cells CTLA-4 was increased after RV infection only in the
      asthmatic group. Levels of CD80 and CD86 in the control cultures were lower in
      the asthmatic group. RV infection induced a significant increase of CD80 on
      monocytes and of CD86 on B cells, which occurred in both groups but were less
      marked in atopic asthmatic subjects. CONCLUSION: Exposure of PBMC to RV is able
      to activate the antigen presentation machinery. Differences between normal and
      atopic asthmatic individuals are compatible with the hypothesis that an aberrant
      immune response to RV may be involved in the development of acute exacerbations
      in atopic asthmatic subjects.

PMID- 11972600
TI  - Hypertonic saline nasal provocation and acoustic rhinometry.
AB  - BACKGROUND: Hypertonic saline (HTS) acts as an airway irritant in human nasal
      mucosa by stimulating nociceptive nerves and glandular secretion. HTS does not
      change vascular permeability. In asthma, HTS causes airflow obstruction.
      OBJECTIVE: To determine the effect of HTS on mucosal swelling using acoustic
      rhinometry (AcRh). Potential vasodilator effects were controlled by maximally
      constricting mucosal vessels with oxymetazoline (Oxy). METHOD: Normal subjects
      had AcRh before and 30 min after either 0.05% Oxy or saline (0.9% NaCl) nasal
      treatments. Nasal provocations followed immediately with five step-wise
      incremental escalating doses of HTS administered at 6-min intervals. AcRh was
      performed 1, 3 and 5 min after each HTS administration, and then after blowing
      the nose at 5 min. The minimum cross-sectional area (Amin), volume of the
      anterior 6 cm of nasal cavity (V6) and incremental changes from pre-drug
      treatment baseline levels (delta, mean +/- SEM) were calculated. RESULTS: Oxy
      increased Amin by 46% (delta = 0.48 +/- 0.07 cm2, P = 0.0001) and V6 by 53%
      (Delta = 9.9 +/- 1.5 mL, P < 1 x 10-7) during the first 30 min. Saline (vehicle)
      treatment had no effect. The maximum HTS dose had no effect after 1 or 3 min.
      However, in the 4th and 5th minutes there were reductions in Amin (delta = 0.07
      +/- 0.03 cm2, P = 0.035) and V6 (delta = 1.57 +/- 0.42 mL, P = 0.004) with an
      increase in the weight of secretions (delta = 700 +/- 100 mg, P < 0.05). Blowing
      the nose returned Amin and V6 towards baseline. Oxy had no effect on HTS-induced
      changes in Amin, V6, pain, rhinorrhea or weight of secretions. CONCLUSION: HTS
      induced nociceptive nerve stimulation and mucus secretion, and reduced V6 and
      Amin. Oxy caused vasoconstriction but did not alter HTS-induced effects. HTS may
      stimulate neurogenic axon response-mediated glandular secretion that contributes
      to perceptions of nasal obstruction in normal subjects.

PMID- 11972601
TI  - Specific immunoglobulin E and immunoglobulin G antibodies to toluene diisocyanate
      human serum albumin conjugate: useful markers for predicting long-term prognosis
      in toluene diisocyanate-induced asthma.
AB  - BACKGROUND: Our previous study reported that more than 50% of toluene
      diisocyanate (TDI)-induced asthma patients had persistent asthmatic symptoms even
      after complete avoidance. Although specific IgE (sIgE) has been detected in a
      portion of patients with TDI-asthma, a recent investigation suggests that the
      presence of serum specific IgG (sIgG), not sIgE, is more closely associated with
      positive bronchoprovocation test (BPT) results. OBJECTIVE: To evaluate the
      possible role of sIgE and sIgG in predicting long-term prognosis of TDI-asthma.
      MATERIALS AND METHODS: Forty-one TDI-asthma patients whose diagnosis was
      confirmed by TDI-BPT, and 20 unexposed healthy controls were enrolled. Both sIgE
      and sIgG to TDI-human serum albumin (HSA) conjugate were detected by ELISA. All
      patients with persistent asthmatic symptoms took anti-asthmatic medications
      during the follow-up period (mean: 67.5 months) and were instructed to avoid
      exposure to TDI. Airway hyper-responsiveness to methacholine (AHM) was monitored
      every year during the study period. The patients were classified into three
      groups according to changing patterns of AHM and asthmatic symptoms as follows:
      group I, no improvement with persistent asthmatic symptoms (n = 12); group II,
      partial improvement with persistent asthmatic symptoms (n = 13); group III, in
      remission (n = 16). RESULTS: Favourable prognosis was associated with a mild
      degree of AHM at initial diagnosis (P < 0.05). Although there were no significant
      differences in the prevalence of sIgE antibody to TDI-HSA conjugate among the
      three groups (P > 0.05), prevalence of sIgG in group I tended to be higher than
      in group II (0.05 < P < 0.1). However, the levels of sIgG were significantly
      higher in group I than in group II (P = 0.05), whereas levels of sIgE were
      significantly higher in group II than in group I (P = 0.014). No significant
      differences were noted in exposure duration, sex, age, atopic status, and total
      IgE level among the three groups (P > 0.05). CONCLUSION: This study confirmed
      that a favourable outcome is related to a mild degree of AHM and to low levels of
      sIgG to predict persistent asthmatic symptoms, it also suggested that the
      presence of high serum-specific IgE at initial diagnosis may represent a better
      prognosis.

PMID- 11972602
TI  - Do levels of immunoglobulin G antibodies to foods predict the development of
      immunoglobulin E antibodies to cat, dog and/or mite?
AB  - BACKGROUND: In children at high risk of inhalation allergy, food sensitization is
      associated with an increased risk for sensitization to inhalant allergens.
      Furthermore, this association was also found in a cross-sectional study.
      OBJECTIVE: To examine in a prospective study, whether levels of IgG to foods
      (i.e. mixture of wheat and rice, mixture of soy bean and peanut, egg white, cow's
      milk, meat, orange and potato) indicate an increased risk for the future
      development of IgE antibodies to inhalant allergens in a low-risk population and
      whether they can be used as predictors of the subsequent development of IgE
      antibodies in young, initially IgE-negative children. METHODS: Coughing children,
      aged 1-5, visiting their GPs, were tested for IgE antibodies to mite, dog and cat
      (RAST) and IgG (ELISA) to foods. All IgE-negative children were retested for IgE
      antibodies after two years. The IgG results (66 percentiles) of the first blood
      sample were compared to the RAST-scores of the second blood sample. RESULTS:
      After two years, 51 out of 397 (12.8%) originally IgE-negative children, had
      become IgE-positive for cat, dog and/or mite. An increased IgG antibody level to
      wheat-rice (OR = 2.2) and to orange (OR = 2.0) indicated an increased risk of
      developing IgE to cat, dog or mite allergens. In addition to IgG to a mixture of
      wheat-rice and orange; total IgE, breastfeeding, eczema as a baby and age were
      the most important predictors for the subsequent development of IgE to inhalant
      allergens. DISCUSSION: An increased IgG antibody level to a mixture of wheat-rice
      or orange, indicates an increased risk of developing IgE to cat, dog or mite
      allergens. This indicates that excessive activity of the mucosal immune system is
      present before IgE antibodies to airborne allergens can be demonstrated.
      Nevertheless, IgG to foods is not very helpful (with a positive predictive value
      of 16.5%, and negative predictive value of 90.6%) in identifying individual
      children at risk in clinical practice. However, besides other risk factors, IgG
      to wheat-rice and to orange could be useful as a screening test for studies in
      the early identification, i.e. before IgE antibodies can be detected, of children
      with an increased risk of developing IgE antibodies in the future.

PMID- 11972603
TI  - Lactobacillus casei strain Shirota suppresses serum immunoglobulin E and
      immunoglobulin G1 responses and systemic anaphylaxis in a food allergy model.
AB  - BACKGROUND: Our previous study using allergen-sensitized murine splenocyte
      cultures has shown that Lactobacillus casei strain Shirota (LcS), a lactic acid
      bacterium widely used as a starter for fermented milk products, suppresses IgE
      production through promoting a dominant Th1-type response mediated by IL-12
      induction. OBJECTIVE: We tried to evaluate the ability of LcS to suppress both
      IgE response and allergic reactions in vivo using a food allergy model with
      ovalbumin-specific T cell receptor transgenic (OVA-TCR-Tg) mice. METHODS: The
      ability of heat-killed LcS to induce IL-12 in serum was tested. OVA-TCR-Tg mice
      were fed a diet containing OVA for 4 weeks and injected with LcS
      intraperitoneally three times in the first week of this period. Cytokine and
      antibody secretion by splenocytes, and serum IgE and IgG1 responses were
      examined. The inhibitory effect of LcS on systemic anaphylaxis induced by
      intravenous challenge of OVA-fed OVA-TCR-Tg mice with OVA was also tested.
      RESULTS: Intraperitoneal injection of LcS induced an IL-12 response in the serum
      of OVA-TCR-Tg mice. In the food allergy model, LcS administration skewed the
      pattern of cytokine production by splenocytes toward Th1 dominance, and
      suppressed IgE and IgG1 secretion by splenocytes. The ability of LcS to modulate
      cytokine production was blocked by anti-IL-12 antibody treatment. LcS also
      inhibited serum OVA-specific IgE and IgG1 responses and diminished systemic
      anaphylaxis. CONCLUSION: LcS administration suppresses IgE and IgG1 responses and
      systemic allergic reactions in a food allergy model, suggesting a possible use of
      this lactic acid bacterium in preventing food allergy.

PMID- 11972604
TI  - Oxidant stress induces gamma-glutamylcysteine synthetase and glutathione
      synthesis in human bronchial epithelial NCI-H292 cells.
AB  - BACKGROUND: The bronchial epithelium is exposed to reactive oxygen species (ROS)
      derived from cigarette smoke, air pollutants and activated leucocytes.
      Glutathione (GSH) prevents ROS-mediated loss of cell function, tissue injury and
      inflammation, and its synthesis is regulated by gamma-glutamylcysteine synthetase
      (gamma-GCS). However, the capacity of bronchial epithelial cells to adapt to
      oxidative stress and the mechanisms involved are not known. OBJECTIVE: To
      investigate the effects of oxidative stress on the regulation of GSH synthesis in
      human bronchial epithelial (NCI-H292) cells. METHODS: NCI-H292 cells were exposed
      to menadione and intracellular GSH concentrations were measured by
      spectrophotometry. gamma-GCS activity was measured by HPLC assay and changes in
      gamma-GCS mRNA by Northern blotting. RESULTS: Exposure to menadione (MQ, 10-200
      microm, 30-120 min) decreased total cellular GSH content, measured immediately
      after exposure to MQ. However, GSH content measured 6-12 h after withdrawal of
      the oxidant stress (MQ, 50 microm, 30 min), increased c. two fold over baseline
      levels (P < 0.001). gamma-GCS activity measured 6 h (21.7 +/- 3.4 nmol/min/mg,
      SD, n = 5, P < 0.01) or 12 h (23.2 +/- 4.6, P < 0.001) after MQ treatment was
      also significantly increased compared with untreated cells (12.8 +/- 1.0).
      Similarly, gamma-GCS mRNA expression increased 1.3-1.6-fold relative to GAPDH
      mRNA, 3-6 h after MQ treatment. The MQ-induced increase in gamma-GCS mRNA
      expression was completely inhibited by actinomycin D. CONCLUSIONS: Bronchial
      epithelial (NCI-H292) cells respond rapidly and sensitively to oxidant stress,
      and this adaptive response is mediated by increased gamma-GCS mRNA transcription
      and enzyme activity.

PMID- 11972605
TI  - Bronchial inflammation in corticosteroid-sensitive and corticosteroid-resistant
      asthma at baseline and on oral corticosteroid treatment.
AB  - BACKGROUND: Pathophysiology of corticosteroid (CS)-resistant asthma remains
      incompletely understood. OBJECTIVE: To determine if failure of asthma to
      clinically improve with CS is due to a defective response of airway bronchial
      inflammation to these drugs. METHODS: Twenty-one asthmatics having a decreased
      baseline FEV1 that improved >or= 30% with inhaled beta2 agonist got bronchial
      biopsies before and at the end of an oral CS treatment (methylprednisolone 40 mg
      daily for 14 days). They were arbitrarily divided into two groups according to
      baseline FEV1 improvement following this treatment: >or= 23% designated as CS
      sensitive (CSS) (n = 10) and < 15% as CS-resistant (CSR) (n = 11). RESULTS:
      Before oral CS, counts of bronchial mucosa inflammatory cells identified by
      immunohistochemistry (CD3, MBP, tryptase, CD68, neutrophil elastase and CD25 for
      lymphocytes, eosinophils, mast cells, macrophages, neutrophils and IL-2
      receptors, respectively) were similar in CSS and CSR subjects. Oral CS decreased
      CD3+ cell counts (medians: 60-20 cells/mm(2); P = 0.014) and MBP+ cell counts
      (medians: 19-4 cells/mm(2); P = 0.03) in CSS asthmatics, but only tryptase+ cell
      counts in CSR asthmatics (medians: 30-18 cells/mm(2); P = 0.05). Few bronchial
      neutrophil elastase+ cells were observed and their counts were similar in the two
      groups of asthmatics before and when on oral CS (all medians: = 2 cells/mm(2)).
      CONCLUSIONS: These data show that, in these subjects with moderate to severe
      asthma, lymphocytes and eosinophils constitute most of the inflammatory cells
      infiltrating the bronchial mucosa. They also demonstrated that clinical impaired
      response to CS is associated with a persistent bronchial mucosa cellular
      infiltrate despite oral CS treatment. Additional studies are required to
      determine the role of this CS-resistant bronchial inflammation in the impaired
      asthma clinical response to these drugs.

PMID- 11972606
TI  - Specific monoclonal antibodies and human immunoglobulin E show that Hev b 5 is an
      abundant allergen in high protein powdered latex gloves.
AB  - BACKGROUND: Hev b 5 is a major latex allergen recognized predominantly by latex
      allergic health care workers (HCWs). Recombinant Hev b 5 (rHev b 5) was
      previously expressed as a fusion protein with maltose binding protein (MBP),
      itself an immunogenic molecule; therefore non-fusion rHev b 5 is desirable.
      Moreover, standardized immunological assays for the detection of Hev b 5 are
      currently lacking and may have important implications for both allergen avoidance
      and diagnosis in latex allergy. OBJECTIVES: To generate and use Hev b 5-specific
      mAbs to determine the relative abundance of Hev b 5 in different latex extracts,
      correlating this with the IgE reactivity of latex-allergic HCWs and to produce
      non-fusion rHev b 5. METHODS: For the production of mAbs, mice were immunized
      with rHev b 5/MBP fusion protein and mAbs selected with rHev b 5/MBP but not MBP
      reactivity. The mAb reactivity was compared with polyclonal IgE from latex
      allergic HCWs using direct and inhibition ELISA and immunoblot assays.
      Recombinant Hev b 5 was expressed and purified in the pPROEX-HTa bacterial
      expression system. RESULTS: Four Hev b 5-specific mAbs were produced.
      Immunoblotting and ELISA using the mAbs indicate abundant Hev b 5 in high protein
      powdered latex glove extracts as compared with crude latex sap extracts. High
      quality surgical gloves with no detectable protein have no detectable Hev b 5.
      Inhibition ELISAs using serum IgE from latex-allergic HCWs and Hev b 5-specific
      mAbs gave strong correlation. Non-fusion recombinant Hev b 5 was successfully
      expressed and purified, showing reactivity with both the Hev b 5-specific mAbs
      and serum IgE of latex-allergic HCWs. CONCLUSION: Hev b 5-specific mAbs and human
      IgE from latex-allergic HCWs demonstrate the greater content of Hev b 5 in high
      protein powdered glove extracts. This may explain the observed higher frequency
      of sensitization to this allergen in HCWs.

PMID- 11972607
TI  - Assessment of cross-reactivity between Japanese cedar (Cryptomeria japonica)
      pollen and tomato fruit extracts by RAST inhibition and immunoblot inhibition.
AB  - BACKGROUND: An association between pollinosis and sensitivity to fruits and
      vegetables has been reported. Although Japanese cedar (Cryptomeria japonica)
      pollinosis is one of the most widespread diseases in Japan, there have been no
      reports demonstrating cross-reactivity between Japanese cedar pollen and other
      plant food. OBJECTIVE: The aim of this study was to demonstrate cross-reactivity
      between Japanese cedar pollen and tomato fruit (Lycopersicon esculentum) using
      RAST inhibition and immunoblot inhibition. METHODS: The RAST and immunoblot
      inhibition were performed using sera from patients with oral allergy syndrome
      (OAS) after ingesting fresh tomatoes. We identified some proteins that took part
      in cross-reactive IgE by the determination of N-terminal amino acid sequences and
      a homology search through the SWISS-PROT database. RESULTS: In the RAST
      inhibition, the bindings of IgE from the sera from four out of five (4/5)
      subjects to Japanese cedar pollen discs were inhibited by more than 50% by
      preincubation of the serum with tomato fruit extracts. Likewise, the IgE bindings
      to tomato fruit discs were inhibited more than 50% by Japanese cedar pollen
      extracts in 3/5 sera. In immunoblot inhibition, IgE binding activities of some
      protein bands on both membranes were decreased by heterologous inhibitors.
      However, the combinations of these protein bands involved in cross-reactivity
      were different between patients. CONCLUSION: We have demonstrated cross
      reactivity between Japanese cedar pollen and tomato fruit using RAST inhibition
      and immunoblot inhibition.

PMID- 11972608
TI  - Proliferative effects of eosinophil lysates on cultured human airway smooth
      muscle cells.
AB  - BACKGROUND: The hypertrophy/hyperplasia of airway smooth muscle (ASM) cells is
      one of the characteristic features of bronchial asthma. This structural change
      leads to the thickening of airway walls resulting in the amplification of airway
      narrowing. However, the pathogenesis of this structural change has not yet been
      determined. Eosinophils, which play a pathogenic role in asthma, have been
      demonstrated to have proliferative effects on fibroblasts and vascular smooth
      muscle cells. OBJECTIVE: We attempted to investigate the potential of eosinophils
      to induce the proliferation of ASM cells. METHODS: We examined the effect of
      lysates of eosinophils purified from peripheral blood of healthy donors on
      cultured human ASM cell proliferation. RESULTS: Eosinophil lysates significantly
      induced ASM cell proliferation in time- and dose-dependent manners, reaching a
      maximum on day 6 at 50% of eosinophil lysates (6.0 +/- 0.7 x 104 [mean +/- SD]
      /well, n = 5 vs. 4.5 +/- 1.1 x 104/well, n = 5; P < 0.05). This proliferative
      activity was heat-sensitive and recovered in the soluble fraction of the
      eosinophil lysates. Furthermore, the molecular weight of the mitogenic activity
      in the soluble fraction was identified as lower than 10 kDa. The inhibitory
      activity to ASM cell proliferation was also found in the insoluble fraction of
      the lysates. CONCLUSION: These results indicate that circulating eosinophils
      store mitogenic activity for ASM cells, suggesting that eosinophils might
      contribute to the development of the hyperplasia of ASM cells in asthmatics
      through the release of the stored mitogenic activity upon stimulation at the site
      of inflammation.

PMID- 11972609
TI  - Effects of birch pollen and traffic particulate matter on Th2 cytokines,
      immunoglobulin E levels and bronchial hyper-responsiveness in mice.
AB  - BACKGROUND: Health effects due to air pollution arising from motor vehicles are a
      major public and political concern world-wide. Epidemiological studies have shown
      that the manifestations of asthma are increased by air pollution in already
      affected individuals. OBJECTIVE: To investigate the potential role of air
      polluted tunnel dust (traffic particulate matter, TPM) or pure carbon core
      particles in the initiation and persistence of experimental allergic
      inflammation. METHODS: BP2 mice were immunized with birch pollen alone (group B)
      or pollen together with TPM (group A), or with birch pollen and Al(OH)3 (group
      C), or with birch pollen and carbon core particles (group D). Before methacholine
      challenge they were challenged intranasally and thereafter bronchial hyper
      reactivity (BHR) was evaluated in a whole-body plethysmograph. Levels of Th2
      cytokines, fibronectin and lactate dehydrogenase (LDH) were determined, and
      differential counts were performed in the bronchoalveolar lavage (BAL) fluid.
      Sera were collected for determination of antibody titres and cytokine levels.
      RESULTS: Specific IgE titres, BHR, the number of recruited eosinophils and levels
      of fibronectin and LDH in BAL were increased in mice immunized and challenged
      with a mixture of birch pollen and TPM. However, mice immunized with birch pollen
      alone and challenged intranasally with pollen or a mixture of pollen and TPM
      demonstrated the highest levels of IL-4 and IL-5. CONCLUSION: This study
      highlights the importance of the exposure to a combination of particulate matters
      and pollen allergens, in the induction of allergic disease in the airways, and we
      have demonstrated that polluted tunnel dust has an effect on both the
      inflammatory and immunological components of experimental allergy. Immunization
      and challenge with carbon core particles together with birch pollen increased
      neither the BHR nor the specific IgE production significantly. Our results
      therefore strongly suggest that it is most likely to be the organic phase bound
      to the carbon core of the diesel exhaust particles that might have an important
      adjuvant effect in the induction of experimental allergy.

PMID- 11972610
TI  - Blockade of superoxide generation prevents high-affinity immunoglobulin E
      receptor-mediated release of allergic mediators by rat mast cell line and human
      basophils.
AB  - BACKGROUND: Previous studies have shown that rat peritoneal mast cells and mast
      cell model rat basophilic leukaemia (RBL-2H3) cells generate intracellular
      reactive oxygen species (ROS) in response to antigen challenge. However, the
      physiological significance of the burst of ROS is poorly understood. OBJECTIVE:
      The present study was undertaken to investigate the role of superoxide anion in
      mediator release in rat and human cell systems. METHODS: RBL-2H3 cells were
      directly stimulated with anti-rat FcepsilonRI alpha-subunit monoclonal antibody
      (mAb). For the analysis of human cell system, leucocytes were isolated by dextran
      sedimentation from healthy volunteers or from patients, and challenged either
      with anti-human FcepsilonRI mAb or with the relevant antigens. Superoxide
      generation was determined by chemiluminescence-based methods. The releases of
      histamine and leukotrienes (LT)s were determined by enzyme-linked immunosorben
      assay (ELISA). RESULTS: Cross-linking of FcepsilonRI on RBL-2H3 cells or on human
      leucocytes from healthy donors by the anti-FcepsilonRI mAb resulted in a rapid
      generation of superoxide anion, as determined by chemiluminescence using
      superoxide-specific probes. Similarly, leucocytes from patients generated
      superoxide anion in response to the challenge with the relevant allergen but not
      with the irrelevant allergen. Furthermore, diphenyleneiodonium (DPI), a well
      known inhibitor of flavoenzymes suppressed the superoxide generation and the
      release of histamine and LTC4 induced by the anti-FcepsilonRI mAb or by allergen
      in parallel. CONCLUSION: These results indicate that both RBL-2H3 cells and human
      basophils generate superoxide anion upon FcepsilonRI cross-linking either by
      antibody or by allergen challenge and that blockade of the generation prevents
      the release of allergic mediators. The findings strongly support the role of
      superoxide generation in the activation of mast cells and basophils under both
      physiological and pathological conditions. The findings suggest that drugs
      regulating the superoxide generation have potential therapeutic use for allergic
      disorders.

PMID- 11972611
TI  - Cellular kinetics of an allergic-type response in a sheep mammary gland model of
      inflammation.
AB  - BACKGROUND: Tissue recruitment of eosinophils and activated lymphocytes is a
      characteristic feature of allergic reactions. However, little is known about the
      involvement of specific adhesion molecules in the traffic of leucocytes during
      the allergic response. OBJECTIVE: To use a sheep mammary infusion model to
      characterize the kinetics of cell recruitment and expression of cellular adhesion
      molecules and activation markers on eosinophils and lymphocytes involved in an
      allergic-type response. METHODS: Mature non-lactating ewes were primed and
      challenged by direct infusion of the mammary glands with nematode larvae. Using a
      non-invasive method of saline infusion and 'milking' of the glands, large numbers
      of inflammatory cells were repeatedly sampled over 10 to 96 h following their
      migration into the mammary gland lumen, and analyzed by 2-colour flow cytometry.
      RESULTS: Leucocyte recruitment into the mammary lumen was characterized by two
      separate phases involving an acute neutrophilic response at 10 h post-challenge,
      followed by a dramatic reduction in neutrophils and appearance of eosinophils and
      activated lymphocytes. From 48 h post-challenge, eosinophils were predominant and
      represented 40 to 65% of leucocytes in the mammary lavage (MAL). Increases in
      activated CD4+ T cells and gammadelta+ T cells were also observed at this time
      point. The kinetics of expression of cell surface molecules on eosinophils and
      lymphocytes in blood and MAL were compared during the course of the allergic-type
      reaction. Adhesion molecule expression on lymphocytes was modulated following
      allergen challenge and an activation of MAL vs. blood lymphocytes was seen during
      the later stages of the allergic response. Eosinophil expression of VLA-4 and l
      selectin was down-regulated compared with blood at all time-points examined.
      There were high levels of expression of CD11b and CD44 on eosinophils during the
      early compared to the late-phase of the allergic reaction. CONCLUSION: These
      results indicate the existence of two separate mechanisms of eosinophil
      recruitment during the allergic inflammatory response.

PMID- 11972613
TI  - Cysteinyl leukotriene-dependent interleukin-5 production leading to eosinophilia
      during late asthmatic response in guinea-pigs.
AB  - BACKGROUND: Allergic airway eosinophilia is suppressed by cysteinyl leukotriene
      (CysLT) receptor (CysLT1 receptor) antagonists in several species including
      humans and guinea-pigs, suggesting that CysLTs are directly or indirectly
      involved in induction of the response. OBJECTIVE: We examined the effect of CysLT
      antagonists (pranlukast and MCI-826) on antigen inhalation-induced eosinophilia
      in peripheral blood and lung, and on IL-5 activity in serum during late increase
      of airway resistance (late asthmatic response, LAR) in sensitized guinea-pigs.
      METHODS: Guinea-pigs inhaled ovalbumin (OVA) + Al(OH)3 and OVA mists alternately
      for sensitization and challenge, respectively, once every 2 weeks. At the fifth
      challenge, the effects of CysLT antagonists and an anti-IL-5 antibody (TRFK-5) on
      the occurrence of LAR, and blood and lung eosinophilia, which appeared at 5 h
      after challenge, were examined. The time-course of IL-5 activity in the serum
      after the challenge was evaluated by measuring in vitro 'eosinophil survival
      prolongation activity'. The influence of CysLT antagonists on IL-5 activity was
      assessed. RESULTS: CysLT antagonists and TRFK-5 completely abolished blood and
      lung eosinophilia. LAR was suppressed by both MCI-826 and TRFK-5 by 40-50%. Sera
      obtained from sensitized, challenged animals 3 h and 4 h after challenge induced
      an obvious prolongation of eosinophil survival. The activity of the sera was
      completely neutralized by prior exposure to TRFK-5, suggesting that it reflected
      IL-5 activity. Increased IL-5 activity in the serum was inhibited by both
      pranlukast and MCI-826 by over 90%. CONCLUSIONS: CysLTs produced after antigen
      provocation sequentially induced IL-5 production from some immune component cells
      via CysLT1 receptor activation. Thus, it is likely that CysLTs indirectly cause
      antigen-induced eosinophilia through IL-5 production.

PMID- 11972614
TI  - Effects of post-inhalation treatment with interleukin-12 on airway hyper
      reactivity, eosinophilia and interleukin-18 receptor expression in a mouse model
      of asthma.
AB  - BACKGROUND: Correcting Th1/Th2 imbalance with administration of IL-12 before and
      during antigen challenge holds therapeutic promise in asthma. However, the
      effects of IL-12 on the established asthmatic responses have not fully been
      examined. OBJECTIVE: We investigated whether IL-12 administered after antigen
      challenge could diminish airway hyper-reactivity (AHR) and eosinophilia in mice
      actively sensitized to ovalbumin. We also have investigated the ability of
      administered IL-12 to induce IL-18 receptor (IL-18R) expression that may lead
      possible synergic action of IL-12 with endogenous IL-18. METHODS: C57BL/6 mice
      immunized to ovalbumin (OVA) by intraperitoneal (i.p.) injection, were challenged
      three times with an aerosol of OVA every second day for 8 days. Recombinant IL-12
      (500 ng) was intravenously administered on a single occasion 1 h after the final
      challenge of mice. Mice were analysed for effects of IL-12 on AHR, inflammatory
      cell infiltration and cytokine levels in lung tissue as well as serum
      immunoglobulin (Ig) E levels. Immunohistochemistry for IL-18R was performed using
      rat monoclonal antibody specific for murine IL-18Ralpha (IL-1 receptor related
      protein; IL-1Rrp). RESULTS: An intravenous IL-12 administration diminished AHR,
      pulmonary eosinophilia and T lymphocyte infiltration, serum IgE, IL-4 and IL-13
      in lung tissue. Expression of IL-18R was induced in the mononuclear cells in the
      lung of mice exposed to OVA. IL-12 administration enhanced the IL-18R expression
      compared with the control. CONCLUSION: These data indicate that IL-12 can
      attenuate established antigen-induced AHR and inflammation. In this mechanism it
      would be interpreted as follows: IL-12 administration in OVA-challenged mice
      decreased IL-4 production and IgE production thereafter through direct effect on
      inhibiting the activation of established Th2 cells response and also combined
      effect with up-regulation of IL-18R expression by inflammatory cells in the lung.

PMID- 11972612
TI  - Interleukin-12 inhibits eosinophil differentiation from bone marrow stem cells in
      an interferon-gamma-dependent manner in a mouse model of asthma.
AB  - BACKGROUND: Intrapulmonary administration of IL-12 has been shown to inhibit the
      number of eosinophils in lung murine models of asthma, but the precise mechanism
      of this inhibition has not been reported. The purpose of this study was to
      examine whether IL-12 treatment inhibits bone marrow eosinophilopoiesis, and to
      elucidate the role of IFN-gamma in this process. OBJECTIVE: To elucidate the in
      vivo and in vitro effects of IL-12 on eosinophil differentiation from murine bone
      marrow (BM) stem cells, and to examine the mechanistic role of IFN-gamma in this
      process. METHODS: Allergen-sensitized BALB/c mice were administered low doses of
      intranasal IL-12 at the time of allergen challenge, and the number of eosinophils
      in BM was determined 3 days later. The direct actions of IL-12 on eosinophil
      differentiation from BM cells were determined in vitro. The mechanistic role of
      IFN-gamma was assessed by measuring IFN-gamma induction by IL-12 in BM cell
      cultures, and through the use of IFN-gamma KO mice. RESULTS: Treatment of
      allergic mice with intrapulmonary IL-12 (1 ng or 10 ng) reduced eosinophils in BM
      by 43%. Culture of BM cells from allergen-sensitized mice with IL-3 + IL-5
      induced eosinophil differentiation in vitro. Addition of IL-12 to these cultures
      inhibited eosinophil differentiation, with maximal inhibition (45%) occurring at
      10 ng/mL IL-12 concentration. IL-12 induced IFN-gamma production from BM
      cultures, and failed to inhibit eosinophil differentiation in IFN-gamma-knockout
      mice, indicating a critical mechanistic role for IFN-gamma. CONCLUSION: This
      study demonstrates that IL-12 selectively inhibits BM eosinophilopoiesis, and
      that this effect is mediated by IFN-gamma. Intrapulmonary IL-12 has suppressive
      effects on BM eosinophilopoiesis that may represent a novel mechanism
      contributing to the anti-eosinophilic effects of IL-12 in allergic airway
      disease.

PMID- 11972615
TI  - A voyage of discovery: cholera, climate and complexity.

PMID- 11972616
TI  - Community shifts in a seeded 3-chlorobenzoate degrading membrane biofilm reactor:
      indications for involvement of in situ horizontal transfer of the clc-element
      from inoculum to contaminant bacteria.
AB  - Pseudomonas putida BN210, carrying the self- transferable clc-element encoding
      degradation of 3-chlorobenzoate on the chromosome, was used as inoculum in
      different membrane biofilm reactors treating 3-chlorobenzoate-contaminated model
      wastewater. Analysis of the bacterial population in the effluent and in the
      biofilm showed the loss of BN210 beyond detection from the reactors and the
      appearance of several novel 3-chlorobenzoate mineralizing bacteria mainly
      belonging to the beta-proteobacteria. In contrast, in non-inoculated reactors, no
      3-chlorobenzoate degradation was observed and no 3-chlorobenzoate degraders could
      be recovered. Southern blots hybridization of genomic DNA using clc-element
      specific probes and FIGE analysis indicated the presence of the complete clc
      element in one or more copies in the isolates. Moreover, the isolates could
      transfer the clc genes to Ralstonia metallidurans recipients. Two representative
      reactor isolates, Ralstonia sp. strains KP3 and KP9 demonstrated a higher growth
      rate on 3-chlorobenzoate than strain BN210 in batch cultures. When BN210, KP3 and
      KP9 were simultaneously inoculated in a membrane reactor supplied with 3
      chlorobenzoate, strain KP3 outcompeted the two other strains and remained the
      major 3-chlorobenzoate degrading population in the reactor. Our data suggest that
      in situ horizontal transfer of the clc-element from the inoculum to contaminant
      bacteria in the reactors was involved in the establishment of novel 3
      chlorobenzoate degrading populations that were more competitive under the defined
      reactor conditions than the inoculum strain.

PMID- 11972617
TI  - Beta-glucose 1-phosphate-interconverting enzymes in maltose- and trehalose
      fermenting lactic acid bacteria.
AB  - Maltose and trehalose catabolic pathways are linked through their common enzyme,
      beta-phosphoglucomutase, and metabolite, beta-glucose 1-phosphate, in Lactococcus
      lactis. Maltose is degraded by the concerted action of maltose phosphorylase and
      beta-phosphoglucomutase, whereas trehalose is assimilated by a novel pathway,
      including the recently discovered enzyme, trehalose 6-phosphate phosphorylase,
      and beta-phosphoglucomutase. In the present study, 40 strains of lactic acid
      bacteria were investigated for utilization of metabolic reactions involving beta
      glucose 1-phosphate. All genera of the low G+C content lactic acid bacteria
      belonging to the clostridial subbranch of Gram-positive bacteria were represented
      in the study. The strains, which fermented maltose or trehalose, were
      investigated for beta-phosphoglucomutase, maltose phosphorylase and trehalose 6
      phosphate phosphorylase activity, as indications of maltose and trehalose
      catabolic pathways involving beta-glucose 1-phosphate interconversions. Eighty
      per cent of all strains fermented maltose and, of these strains, 63% were shown
      to use a maltose phosphorylase/beta- phosphoglucomutase pathway. One-third of the
      strains fermenting trehalose were found to harbour trehalose 6-phosphate
      phosphorylase activity, and these were also shown to possess beta
      phosphoglucomutase activity. Mainly L. lactis and Enterococcus faecalis strains
      were found to harbour the novel trehalose 6-phosphate phosphorylase/beta
      phosphoglucomutase pathway. As lower beta-glucose 1-phosphate interconverting
      enzyme activities were observed in the majority of glucose-cultivated lactic acid
      bacteria, glucose was suggested to repress the synthesis of these enzymes in most
      strains. Thus, metabolic reactions involving the beta-anomer of glucose 1
      phosphate are frequently found in both maltose- and trehalose-utilizing lactic
      acid bacteria.

PMID- 11972618
TI  - Persistence of Escherichia coli O157:H7 in soil and on plant roots.
AB  - Soil microcosms were inoculated with Escherichia coli O157:H7 to test persistence
      in fallow soil, on roots of cover crops and in presence of manure. In fallow
      soils, E. coli O157:H7 persisted for 25-41 days, on rye roots for 47-96 days and
      on alfalfa roots, in a silt loam soil, for 92 days whereas on other legumes
      persistence ranged from 25-40 days, similar to fallow soil. Manure did not seem
      to affect the persistence of E. coli O157:H7 in these soils. Indigenous and
      manure-applied coliform populations often decreased faster when E. coli O157:H7
      was applied, indicating possible competition between microflora. Coliform
      populations in microcosms not inoculated with E. coli O157:H7 decreased more
      slowly or increased. Microbial community analyses showed little effect for E.
      coli O157:H7 inoculation or addition of manure. Microbial community metabolic
      activity was enhanced from rye roots after 14 days and by 63 days from alfalfa
      roots. Microbial community lactose utilization increased over time on rye roots
      in all soils and on alfalfa roots in a silt loam soil when E. coli O157:H7 was
      inoculated. Lactose utilization also increased for uninoculated rye roots, soil
      around rye roots and in some fallow soils. Our data suggest that clay increases
      persistence and activity of E. coli O157:H7 and other coliforms. In frozen soil
      stored for over 500 days, E. coli O157:H7 was viable in 37% of tested samples. In
      summary, E. coli O157:H7 persisted longer and activity was enhanced with some
      cover crops in these soils due to plant roots, the presence of clay and freezing.

PMID- 11972619
TI  - Microenvironments and microbial community structure in sediments.
AB  - The aim of this study was to explore the potential of a combined chemical and
      microbiological approach as part of a study of organic carbon oxidation processes
      in sediments. An assessment of microbiological diversity using molecular
      techniques was carried out in combination with high resolution chemical
      measurements at the sediment-water interface of a coastal lagoon affected by
      eutrophication in autumn 2000. There was a 0.2 mm overlap between the O2 and H2S
      profiles. pH showed a maximum just above the sediment-water interface coinciding
      with an oxygen maximum, suggesting photosynthetic activity, and a minimum
      coinciding with the O2-H2S interface. The redox potential was high in bottom
      water and surface sediment, reflecting the presence of oxygen and oxides, and
      reached low values after a step-wise decrease at -18 mm. Reduction of Fe occurred
      within the biofilm at the O2-H2S interface and was mostly due to reduction by
      H2S. The elevated concentrations of dissolved Mn in the oxic water may have been
      caused either by in situ production within organic aggregates or lateral water
      flow from sites nearby at which Mn2+ diffuses out of the sediment. Sequences
      related to sulphur chemolitotrophs were retrieved from the biofilm samples, which
      is consistent with the small overlap between O2 and H2S observed in this biofilm.
      Although the resolution of techniques used was different, sequencing results were
      consistent with chemical data in delineating the same horizons according to
      redox, pH or ecological properties.

PMID- 11972621
TI  - Reduction of Fe(III) oxide by methanogens in the presence and absence of
      extracellular quinones.
AB  - Five methanogens (Methanosarcina barkeri MS, Methanosphaera cuniculi 1R7,
      Methanobacterium palustre F, Methanococcus voltaei A3 and Methanolobus vulcani PL
      12/M) were investigated for their ability to reduce Fe(III) oxide and the soluble
      quinone anthraquinone-2,6-disulphonate (AQDS). Two species (M. barkeri and M.
      voltaei) reduced significant amounts of Fe(III) oxide using hydrogen as the
      electron donor, and 0.1 mM AQDS greatly accelerated Fe(III) reduction by these
      organisms. Although Fe(III) appeared to inhibit growth and methanogenesis of some
      strains, hydrogen partial pressures under donor-limited conditions were much
      lower (<0.5 Pa) in the presence of Fe(III) than in normal media (1-10 Pa) for all
      species except for M. vulcani. These results demonstrate that electrons were
      transferred to Fe(III) by hydrogen-utilizing methanogens even when growth and
      methanogenesis were inhibited. All species except the obligate methylotroph M.
      vulcani were able to reduce AQDS when their growth substrates were present as
      electron donors, and rates were highest when organisms used hydrogen as the
      electron donor. Purified soil humic acids could also be reduced by the AQDS
      reducing methanogens. The ability of methanogens to interact with extracellular
      quinones, humic acids and Fe(III) oxides raises the possibility that this
      functional group of organ-isms contributes to Fe(III) and humic acid reduction
      under certain conditions in the environment and provides an alternative
      explanation for the inhibition of methanogenesis in some Fe(III)-containing
      ecosystems.

PMID- 11972620
TI  - Following spread of fire blight in Western, Central and Southern Europe by
      molecular differentiation of Erwinia amylovora strains with PFGE analysis.
AB  - Fire blight has been detected recently in several areas of northern Spain and
      north-eastern Italy. To follow spread of the disease within Europe, more than 120
      Erwinia amylovora strains isolated from 1957-1900 in England, France, Germany,
      The Netherlands, Belgium, Poland, Italy and Spain were assayed using pulsed-field
      gel electrophoresis (PFGE) analysis of genomic DNA after XbaI digestion. Pattern
      types Pt1 and Pt4 were found for strains from England. Pt1 was also found in
      central Europe and eastern France, Pt4 in western France. Pt2 appeared first in
      Egypt, from where strains with this pattern disseminated northwards as far as
      into the Balkans. Pt3 was typical for northern France and Belgium. Strains from
      Spain displayed the pattern types Pt3 and Pt4. In Italy, Pt2 was found in the
      south-eastern areas, Pt3 in the north-eastern areas, and Pt1 was found very
      recently in orchards adjacent to the Austrian border, together with Pt3. Despite
      barely controlled trade with fire blight host plants and associated plant
      products within Europe, the PFGE patterns of the E. amylovora isolates were
      ordered indicating sequential spread. On the other hand, the appearance of Pt3 in
      northern Italy and central Spain can be explained by the import of contaminated
      plants by nurseries.

PMID- 11972625
TI  - 36th Annual Meeting of the European Society for Clinical Investigation. Brussels,
      Belgium, 10-13 April 2002. Abstracts.

PMID- 11972622
TI  - Effect of oil pollution on euendolithic cyanobacteria of the Arabian Gulf.
AB  - Microbial euendoliths (true borer) cyanobacteria are carbonate-boring
      microorganisms found in modern and ancient marine environments. Modern
      euendoliths include a wide range of prokaryotes as well as eukaryotes, which have
      been reported world-wide. The importance of euendolithic cyanobacteria concerns
      their role in bio-erosion of calcium carbonate substrates and as ecological
      indicators of shallow, tropical and subtropical marine environments. Arabian Gulf
      ooids from four sites along the east coast of Saudi Arabia have been bored and
      inhabited by several species of euendolithic cyanobacteria. This assemblage of
      different species exists simultaneously within the same ooid grain. Comparisons
      of 1989 and 1992 data reveal a drastic reduction in active euendoliths, and the
      average numbers of colonies in these ooids. This study reveals the harmful effect
      of the 1991 oil spill on these unique microorganisms residing in these ooids.

PMID- 11972627
TI  - Products from human mast cell line cells enhance the production of interferon
      gamma by CD8+ and CD4+ T cells.
AB  - In patients with allergic asthma, T-cell cytokines are implicated in the
      regulation of the local inflammation in the airways. The ability of sensitized
      mast cells to release mediators and cytokines early upon allergen stimulation
      makes them important candidates for local immunoregulation. We have studied the
      effects of human mast cells on T cells with the use of the human mast cell line
      HMC-1. We showed that activated human mast cells or their soluble products
      induced and enhanced the interferon-gamma (IFN-gamma) production by T cells up to
      about 60-fold. The production of interleukin (IL)-4 was hardly affected and that
      of IL-5 was slightly enhanced. The enhancement of IFN-gamma production was
      induced both in polyclonal CD4+ and CD8+ T cells and in CD4+ and CD8+ T-cell
      clones. Further characterization of the factors involved demonstrated a molecular
      mass above 30 000. Our results implicate that by this mechanism mast cells may
      account for a negative feedback system locally down-regulating allergen-induced T
      helper 2 responses via IFN-gamma production by the T cells.

PMID- 11972626
TI  - Genomics and proteomics of allergic disease.
AB  - The world-wide effort to identify susceptibility genes for allergic diseases is
      motivated by the conviction that the identification of disease genes may permit
      the design of new classes of anti-inflammatory compounds. Molecules concerned
      with the allergic reaction, such as cytokines, chemokines, their receptors, major
      histocompatibility complex molecules, and transcription factors, could provide
      the candidate genes of the allergic diseases. On the basis of genetic studies,
      multiple research groups have attempted to identify a susceptibility gene for
      allergy using the candidate gene approach and/or genome-wide screening. Both of
      these approaches suggest genetic heterogeneity of allergic diseases. Many
      variants of candidate genes are or are not associated with particular diseases in
      different ethnic groups and the function of variants is now being investigated.
      Based on the information accumulated thus far and the information on the human
      genome sequence, future advances in research on genetic factors for allergic
      diseases will be likely lead to the establishment of more effective prophylaxis
      and therapy for these diseases.

PMID- 11972628
TI  - A cathelicidin family of human antibacterial peptide LL-37 induces mast cell
      chemotaxis.
AB  - The mast cell is one of the major effector cells in inflammatory reactions and
      can be found in most tissues throughout the body. During inflammation, an
      increase in the number of mast cells in the local milieu occurs, and such
      accumulation requires directed migration of this cell population. As it has
      previously been reported that the human cathelicidin-derived antibacterial
      peptide, LL-37, stimulates the degranulation of mast cells, we hypothesized that
      LL-37 could be a mast cell chemotaxin. The present study shows that LL-37 is a
      potent chemotactic factor for mast cells. The chemotactic response was dose
      dependent and bell-shaped, reaching an optimal concentration of 5 microg/ml. In
      addition, checkerboard analysis showed that cell migration towards this peptide
      was chemotactic rather than chemokinetic. Moreover, Scatchard analysis using 125I
      labelled LL-37-derived peptide revealed that LL-37 has at least two classes of
      receptors, namely high- and low-affinity receptors, on mast cells. Furthermore,
      the competitive binding assay suggested that LL-37 is unlikely to utilize formyl
      peptide receptor-like 1 (FPRL1), a functional LL-37 receptor for neutrophil and
      monocyte migration, on mast cells. In addition, the treatment of cells with
      pertussis toxin and phospholipase C inhibitor, U-73122, inhibited LL-37-mediated
      migration, indicating that LL-37 induces mast cell chemotaxis through a Gi
      protein-phospholipase C signalling pathway. These results show that besides its
      antibacterial activities, LL-37 may have the potential to recruit mast cells to
      inflammation foci.

PMID- 11972629
TI  - T-cell dynamics after high-dose chemotherapy in adults: elucidation of the
      elusive CD8+ subset reveals multiple homeostatic T-cell compartments with
      distinct implications for immune competence.
AB  - Recovery of total T cell numbers after in vivo T-cell depletion in humans is
      accompanied by complex perturbation within the CD8+ subset. We aimed to elucidate
      the reconstitution of CD8+ T cells by separate analysis of putative naive CD95-
      CD28+, memory CD95+ CD28+ and CD28- T cell compartments after acute maximal
      depletion by high-dose chemotherapy (HD-ChT) in women with high-risk breast
      cancer. We found that recovery of putative naive CD8+ CD95- CD28+ and CD4+ CD95-
      CD28+ T cells, was compatible with a thymus-dependent regenerative pathway since
      their recovery was slow and time-dependent, their values were tightly related to
      each other, and their reconstitution patterns were inversely related to age. By
      analysing non-naive T cells, a striking diversion between putative memory T cells
      and CD28- T cells was found. These latter increased early well beyond normal
      values, thus playing a pivotal role in total T-cell homeostasis, and contributed
      to reduce the CD4 : CD8 ratio. In contrast, putative memory T cells returned to
      values not significantly different from those seen in patients at diagnosis,
      indicating that this compartment may recover after HD-ChT. At 3-5 years after
      treatment, naive T cells persisted at low levels, with expansion of CD28- T
      cells, suggesting that such alterations may extend further. These findings
      indicate that CD28- T cells were responsible for 'blind' T-cell homeostasis, but
      support the notion that memory and naive T cells are regulated separately. Given
      their distinct dynamics, quantitative evaluation of T-cell pools in patients
      undergoing chemotherapy should take into account separate analysis of naive,
      memory and CD28- T cells.

PMID- 11972630
TI  - Involvement of ERK, p38 and NF-kappaB signal transduction in regulation of TLR2,
      TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic
      cells.
AB  - Toll-like receptors (TLR) are sentinel receptors capable of recognizing pathogen
      associated molecule patterns (PAMP) such as lipopolysaccharide (LPS) and CpG
      containing oligonucleotides (CpG ODN). TLR2 and TLR4 are major receptors for Gram
      positive and Gram-negative bacterial cell wall components, respectively. TLR9 is
      necessary for CpG signalling. LPS or CpG ODN can activate immature dendritic
      cells (DC) and induce DC maturation characterized by production of cytokines, up
      regulation of co-stimulatory molecules, and increased ability to activate T
      cells. However, little is known regarding the regulation of TLR gene expression
      in mouse DC. In this study, we investigated the regulation of TLR2, TLR4 and TLR9
      gene expression by LPS in murine immature DC. TLR2, TLR4 and TLR9 mRNA were up
      regulated following LPS stimulation. The up-regulation of TLR9 expression
      coincided with significantly increased production of tumour necrosis factor-alpha
      induced by LPS plus CpG ODN. While inhibition of extracellular signal-related
      kinase and NF-kappaB activation suppressed the up-regulation of the expression of
      TLR2, TLR4 and TLR9 mRNA, inhibition of p38 kinase prevented the up-regulation of
      TLR2 and TLR4 mRNA expression but enhanced the up-regulation of TLR9 expression.
      These results demonstrated that TLR2, TLR4 and TLR9 gene expression was
      differently regulated by LPS in mouse immature DC. Up-regulation of TLR2, TLR4
      and TLR9 expression by LPS might promote the overall responses of DC to bacteria
      and help to explain the synergy between LPS and other bacterial products in the
      induction of cytokine production.

PMID- 11972631
TI  - Lack of evidence for aggregation-dependent enhancement of p56lck in the signal
      transduction upon major histocompatibility complex recognition by mature T cells.
AB  - The kinase activity of lymphocyte-specific tyrosine kinase p56lck (Lck) upon
      physiological major histocompatibility complex (MHC) recognition by normal mature
      T cells was examined. Recognition of the target MHC molecules by T cells induced
      phosphorylation of the zeta-chain without obvious enhancement of the background
      Lck activity. There was no sign of enhancement of Lck through putative T-cell
      receptor (TCR)-independent class II MHC/CD4 interactions either. As has been
      reported, cross-linking of CD4 molecules by antibodies induced a marked
      enhancement of Lck activity. However, it did not have an immediate relevance to
      TCR-mediated signal transduction, as judged from the lack of detectable de novo
      phosphorylation of zeta-chain and the absence of functional responses of T cells.
      These results strongly favour the model in which TCR-mediated signal transduction
      does not involve aggregation-dependent enhancement of Lck, suggesting that the
      signal can be triggered simply by the recruitment of already active Lck with
      basal kinase activity through the formation of a TCR/MHC/CD4 ternary complex.

PMID- 11972632
TI  - Peroxisome-proliferator-activated-receptor gamma (PPARgamma) independent
      induction of CD36 in THP-1 monocytes by retinoic acid.
AB  - Retinoic acid (RA) has been shown to regulate cellular growth and differentiation
      of a variety of cell types, including cells of the myelomonocytic lineage. We
      used the monocytic leukaemia cell line THP-1, which differentiates to macrophages
      in response to phorbol 12-myristate 13-acetate (PMA), to investigate the
      regulation by RA of genes in the scavenger receptor type B family (CD36) in human
      monocyte/macrophages. Reverse transcription-polymerase chain reaction and flow
      cytometry demonstrated that, like PMA and the natural peroxisome-proliferator
      activated receptor-gamma (PPARgamma) ligand 15d-PGJ2, RA induced CD36 gene
      expression in these cells. Moreover, RA plus 15d-PGJ2 further enhanced CD36
      protein and mRNA levels over that seen with the RA or PPARgamma compounds alone.
      The PPARgamma antagonist GW9662 was shown to block completely PPARgamma-ligand
      induction of CD36 gene expression, but had little effect on the action of RA. Our
      data indicated that RXR- and RAR-specific ligands (LG153 and TTNPB, respectively)
      were each alone able to increase CD36 mRNA and surface protein levels. By using
      calphostin C, a specific protein kinase C (PKC) inhibitor, we demonstrated that
      induction of CD36 by PMA, as well as by PPARgamma and RXR ligands were dependent
      upon PKC activation. In contrast, activation of CD36 through the RAR pathway was
      not affected by inhibition of PKC activity. Taken together, these data
      demonstrate that RA can up-regulate CD36 expression in human
      monocytes/macrophages. This regulation appears to be predominantly mediated
      through the RAR/RXR pathway of action and, unlike previously described methods of
      CD36 modulation, is independent of PPARgamma and PKC signalling. This study
      suggests a possible role for RA in physiological processes involving the
      scavenger receptor function in cells of the monocyte/macrophage lineage.

PMID- 11972633
TI  - Antigen binding to GM1 ganglioside results in delayed presentation: minimal
      effects of GM1 on presentation of antigens internalized via other pathways.
AB  - Plasma membrane rafts are sphingolipid- and cholesterol-rich patches that
      function as membrane trafficking and surface signalling regions. Ganglioside GM1
      is an integral component of these microdomains, and Escherichia coli enterotoxin
      B subunit (EtxB) is a pentamer that binds with high affinity to GM1 resulting in
      GM1 cross-linking. We previously demonstrated that antigen coupled directly to
      EtxB resulted in enhanced presentation relative to antigen taken up by fluid
      phase endocytosis. Here we demonstrate a new role for GM1 in antigen presentation
      by examining the effects of cross-linking GM1 on the kinetics of presentation and
      processing of antigen by the B-cell receptor (BCR), fluid-phase endocytosis and
      GM1-targeted antigen. EtxB bound to B cells does not augment the subsequent
      kinetics or magnitude of presentation of either BCR-internalized antigen or
      soluble antigen. Moreover, presentation of GM1-bound antigen is significantly
      slower than antigen presentation following BCR-mediated uptake. In contrast to
      the rapid internalization of BCR-bound antigen (which has a half life of 60 min),
      the majority of EtxB-bound antigen forms a plasma membrane depot detectable for
      many hours after initial incubation (and with a half life of 12 hr). We conclude
      that cross-linking of GM1 by EtxB minimally affects the processing and
      presentation of antigens internalized via other pathways. Nevertheless, binding
      of antigens to GM1 results in delayed presentation that has important
      implications for in vivo immunization using GM1-targeted adjuvants.

PMID- 11972634
TI  - Staphylococcal enterotoxin H contrasts closely related enterotoxins in species
      reactivity.
AB  - Staphylococcus aureus enterotoxin H (SEH) belongs to the staphylococcal
      enterotoxin (SE) family of superantigens (SAgs). SEH has structural similarities
      to other SE; however, its biological properties are less well characterized. SEH
      binds with high affinity to human major histocompatibility complex (MHC) class II
      and exhibits strong mitogenic activity in human T cells, although it was found to
      be less potent than the related SEA. Surprisingly and in sharp contrast to
      related SEs, SEH did not possess superantigen activity in murine T cells and T
      cells from three investigated rat strains. However, SEH bound to a high extent to
      murine MHC class II expressing cells and when presented by these cells SEH
      stimulated human T cells to proliferate. Thus, SEH interacts with the murine MHC
      class II molecule in a functional manner. Notably, SEH had an inhibitory effect
      on murine SEA response, demonstrating that SEH interferes with the SEA
      interactions with murine cells. Despite this, murine T cells did not proliferate
      regardless of whether SEH was presented on human or murine MHC class II
      expressing cells. Consequently, SEH differs in species reactivity as compared to
      related SEs and lacks critical properties for T-cell activation in mice. We
      propose that unlike other SEs, SEH does not interact with murine T cells since it
      is not recognized by murine T-cell receptors.

PMID- 11972635
TI  - Role of antiretroviral regimes in HIV-1 patients in reducing immune activation.
AB  - We assessed whether antiretroviral regimes are able to diminish apoptosis and
      markers of lymphocyte activation and restore lymphocyte proliferation. T-cell
      subset, spontaneous and induced apoptosis, CD95 and soluble Fas antigen and cell
      proliferation were analysed in 41 human immunodeficiency virus type 1-positive
      patients. Twenty-five were in asymptomatic stage A and 16 were in stage B/C.
      Thirty-five received antiretroviral treatment: 18 received two inhibitors of
      reverse transcriptase and one protease inhibitor and 17 received three inhibitors
      of reverse transcriptase. Six patients did not receive treatment, for different
      reasons, but continued to participate in the study. Studies were performed at
      baseline, 3, 6 and 12 months. Levels of CD4 increased slightly until 6 months of
      antiretroviral treatment, as a whole, in all the patients treated. Naive CD4
      lymphocytes, as well as memory CD4 lymphocytes, remained constant. Spontaneous
      apoptosis of lymphocytes, after 72 hr of culture, decreased in all patients
      treated, but to a much smaller extent than phytohaemagglutinin-induced apoptosis.
      In both groups treated, levels of soluble Fas decreased until 6 months of
      treatment and then increased again. Lymphocyte proliferation reached normal
      levels after 1 year of treatment. In patients without treatment CD4 cells
      decreased slowly and no modification in activation markers was found.
      Antiretroviral regimes decrease immune activation as well as viral load and this
      deactivation restores lymphocyte proliferation.

PMID- 11972636
TI  - T-cell activation, proliferation and apoptosis in primary Listeria monocytogenes
      infection.
AB  - Listeria monocytogenes infection of mice leads to a rapid expansion of activated
      T cells, followed by a decline in specific cells once the bacteria are
      eliminated. In order to define the relationship between T-cell proliferation and
      activation, and to investigate the role of apoptosis in limiting the expansion,
      the expression of activation markers, uptake of 5-bromo-2'-deoxyuridine (BrdU) in
      vivo and the incidence of apoptosis was investigated. Increased numbers of T
      cells expressing the activated phenotype CD25+, CD44hi and CD62Llo were detected
      4 days after infection. Expression of CD25 (IL-2Ralpha chain) on CD4+ and CD8+ T
      cells peaked at this time and returned to normal by day 7. In contrast, CD44hi
      and CD62Llo persisted, with the maximum proportion occurring at 7 days after
      infection. This was accompanied by a burst of in vivo proliferation of CD4+ and
      CD8+ T cells occurring between day 5 and 7. Apoptosis, which is presumably needed
      to control this expansion of T cells, also peaked at 7 days after infection.
      Apoptosis occurred preferentially amongst T cells which had proliferated. Most
      but not all proliferating T cells had down-regulated their CD62L marker. While
      most apoptotic T cells were CD62Llo, again not all had down-regulated this
      marker. Hence, CD25 expression peaked early, but expression of other activation
      markers, in vivo proliferation and apoptosis coincided after Listeria infection.
      T cells that had proliferated were over-represented in the apoptotic population.

PMID- 11972637
TI  - Purified protein derivative of tuberculin upregulates the expression of vascular
      endothelial growth factor in T lymphocytes in vitro.
AB  - The purpose of this study was to investigate the cellular source and significance
      of vascular endothelial growth factor (VEGF) which, as reported previously, is
      elevated in the sera of pulmonary tuberculous patients. We obtained peripheral
      blood mononuclear cells (PBMCs) from 28 patients with active pulmonary
      tuberculosis, from 11 healthy controls who were positive for purified protein
      derivative of tuberculin (PPD), and from eight healthy individuals who were
      negative for PPD. We incubated the PBMCs with PPD in the presence or absence of
      major histocompatibility (MHC) class I or class II antibody in vitro, and
      measured the VEGF levels of culture supernatants. We also analysed the source of
      cells that secrete VEGF by using flow cytometry with intracellular staining. The
      T lymphocytes of active tuberculous patients secreted a higher level of VEGF than
      those of healthy controls. This production of VEGF was inhibited by adding MHC
      class II antibody. The addition of MHC class I antibody, however, did not
      inhibit. We propose that CD4+ T lymphocytes are almost certainly the cells that
      produce VEGF in response to PPD. VEGF production might be associated with an
      antigen-specific immune reaction via CD4+ T lymphocytes in tuberculosis.

PMID- 11972642
TI  - Current status and future perspectives in the treatment of advanced testicular
      cancer.

PMID- 11972638
TI  - Phosphodiester CpG oligonucleotides as adjuvants: polyguanosine runs enhance
      cellular uptake and improve immunostimulative activity of phosphodiester CpG
      oligonucleotides in vitro and in vivo.
AB  - Bacterial DNA and oligonucleotides (ODN) containing CpG-motifs strongly activate
      cells of the immune system. Accordingly CpG-DNA is a powerful adjuvant in
      vaccination protocols for B-cell as well as for cytotoxic T-cell responses. A
      decisive propensity of CpG-DNA is its capacity to induce preferentially T helper
      type 1 (Th1)-dominated immune responses. To exert its function CpG-DNA has to be
      taken up by responsive cells, e.g. antigen-presenting cells (APC). The rate of
      uptake is influenced by the DNA's backbone modification and critically determines
      activity of CpG-DNA. CpG ODN with a phosphothioate backbone (PTO) are currently
      used for most in vivo and in vitro studies, since PTO modification protects ODN
      from the attack of nucleases. However, after administration of PTO-modified CpG
      ODN long-lasting effects including lymphadenopathy as well as sustained local
      interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) production have been
      reported. To circumvent these restrictions we investigated the effects of DNA
      sequence as well as DNA backbone modification on cellular uptake and resulting
      immunostimulation. We show here that uptake of phosphodiester (PO)-CpG-ODN can be
      strongly enhanced by poly guanosine runs added at the 3' end of the ODN. In
      addition these ODN showed an improved immunostimulatory activity in vivo and in
      vitro. This included protection of mice against lethal Th2-dependent
      leishmaniasis as well as priming of antigen specific Th1 responses. More
      importantly, guanosine-rich PO-CpG-ODN neither induced lymphadenopathy nor
      prolonged cytokine production after local administration. Since these improved PO
      ODN are efficient in vitro and in vivo and lack long lasting undesired effects
      they could be used preferably as adjuvants in vaccination protocols.

PMID- 11972639
TI  - Intranasal administration of a synthetic lipopeptide without adjuvant induces
      systemic immune responses.
AB  - Parenteral injection of a lipopeptide containing a human leucocyte antigen (HLA)
      A*0201-restricted cytotoxic T-lymphocyte (CTL) epitope from the human
      cytomegalovirus (HCMV) immunodominant matrix protein pp65 efficiently induces
      systemic CTL responses in HLA-A*0201 transgenic mice. In this study, we
      demonstrate that intranasal (i.n.) administration of this lipopeptide, covalently
      linked to a universal T helper (Th) epitope (PADRE), also induces potent systemic
      CTL responses. Immune responses were substantially reduced when the unlipidated
      peptide analogue was used (P<0.01). The induced CTL were CD8+, major
      histocompatibility complex (MHC) class I-restricted and CMV specific. Moreover,
      i.n. administration of this lipidated peptide elicited both systemic and local
      mucosal CD4+ T-cell proliferative responses, as well as antigen-specific delayed
      type hypersensitivity (DTH) immune responses. In contrast, mice receiving the
      unlipidated peptide analogue developed substantially reduced Th or DTH responses
      (P<0.05). These results highlight the usefulness and potential of lipopeptides
      delivered via mucosal routes as painless, safe, and non-invasive vaccines.

PMID- 11972643
TI  - Extracorporeal shock wave lithotripsy produces a lower stone-free rate in
      patients with stones and renal cysts.
AB  - BACKGROUND: Renal cysts have a space-occupying effect and therefore can distort
      the pelvicalyceal anatomy. This distortion often produces abnormalities in normal
      urinary drainage. In the same way, it may effect the ability of the kidneys to
      become stone free after extracorporeal shock wave lithotripsy (ESWL). The purpose
      of the current study is to evaluate the effect of renal cysts on the outcome of
      ESWL. METHODS: We studied 15 patients who had renal stones and coexistent renal
      cysts. Four patients had polycystic disease, five patients had multiple cysts and
      six patients has solitary ones. All cysts produced a distortion to the calyceal
      system of the kidneys, a fact confirmed by intravenous urography (IVU) and
      computed tomography (CT). All patients underwent ESWL and their stone-free status
      was evaluated 1 month later by ultrasound and plain kidney ureter bladder (KUB) X
      ray. RESULTS: We had a total 60% (9/15) stone-free patients in our study group
      and a stone fragmentation rate of 100%. Patients with more cysts had lower stone
      free rates. Patients with polycystic kidneys had a 25% (1/4) stone-free rate,
      while patients with multiple cysts and solitary cysts had, 60% (3/5) and 83.3%
      (5/6), respectively. These results are lower than the rates reported in patients
      without renal cysts. CONCLUSIONS: We believe that renal cysts may interfere with
      the passage of stone fragments, due to the impediment of drainage and urinary
      stasis from the stretching and distortion of the calyceal system by the renal
      cysts.

PMID- 11972644
TI  - Significance of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for
      detection of renal cell carcinoma and immunohistochemical glucose transporter 1
      (GLUT-1) expression in the cancer.
AB  - OBJECTIVE: Positron emission tomography (PET) is now primarily used in
      oncological indication owing to the successful application of fluorine-18
      fluorodeoxyglucose (FDG) in an increasing number of clinical indications. Glucose
      transporter 1 (GLUT-1) is recognized as a major early marker of cellular
      malignant transformation. The aims of this study were to assess whether FDG-PET
      is a useful diagnostic tool for renal cell carcinoma and to compare the
      pathologic characteristics. METHODS: Nineteen consecutive patients who had renal
      cell carcinoma were examined using FDG-PET preoperatively. The results of PET
      were then compared to the histology obtained after radical surgery and the
      immunoreactivity of GLUT-1 was also studied. RESULTS: Pathologic examination
      confirmed that all 19 patients suffered from renal cell carcinoma. Increased FDG
      uptake was found in six of the 19 patients (31.5%). The immunohistochemical
      examination of GLUT-1 in renal cell carcinoma produced different results in each
      patient. There was no correlation with GLUT-1 immunoreactivity and FDG-PET
      positivity. CONCLUSION: These results suggest that FDG-PET may not be a useful
      diagnostic tool for renal cell carcinoma.

PMID- 11972645
TI  - Recurrence of renal cell carcinoma more than 5 years after nephrectomy.
AB  - OBJECTIVES: We evaluated clinical features and predictive factors for the
      recurrence of renal cell carcinoma (RCC) developing more than 5 years after
      nephrectomy. METHODS: We retrospectively reviewed 239 patients with RCC who
      underwent surgery for the primary lesion. To identify factors that affected
      recurrence more than 5 years after nephrectomy (delayed recurrence) and its
      clinical outcomes, we performed a multivariate analysis using Cox's proportional
      hazards model and a survival study. RESULTS: Recurrence developing within 5 years
      after nephrectomy (early recurrence) was found in 57 patients and delayed
      recurrence in 11 patients. The multivariate analysis revealed no clinical and
      pathologic features influencing delayed recurrence in 114 patients who survived
      more than 5 years after nephrectomy without having early recurrence. The patients
      with delayed recurrence showed better clinical outcomes than those with early
      recurrence when the rate was determined from the time of recurrence. CONCLUSIONS:
      Although delayed recurrence is not a rare event for patients with RCC, no
      clinical and pathologic factors at the time of the initial treatment can predict
      the recurrence. Patients who are free of recurrence for more than 5 years after
      surgery for a primary lesion should be carefully followed up for delayed
      recurrence.

PMID- 11972646
TI  - Promoting the effects of intravesical instillation of saline on bladder lesion
      development in rats pre-treated with BBN.
AB  - BACKGROUND: At present, immunotherapeutic agents such as bacillus Calmette-Guerin
      (BCG) and anti-tumor chemotherapeutic agents in saline are used intravesically in
      patients with bladder carcinoma. However, of greater significance is the
      possibility that the saline vehicle may itself promote carcinoma development in
      the bladder. METHODS: The potential promoting effects of intravesical
      instillation of saline were assessed in female F344 rats. The animals were
      divided into 3 groups, all of which received 0.05% N-butyl-N-(4
      hydroxybutyl)nitrosamine (BBN) in their drinking water for the first 10 weeks.
      They were then maintained without further treatment (group 1) or received
      intravesical instillations of 0.3 mL of saline or distilled water once a week for
      6 weeks, 15 weeks after the end of the BBN treatment (groups 2 and 3). At 32
      weeks, all the animals were killed and examined immunohistochemically with
      proliferating cell nuclear antigen (PCNA) antibody, as well as by routine
      histopathologic examination. RESULTS: Both the incidence and the number of
      bladder carcinomas were higher in the animals that received instillations of
      saline than in those who did not receive the instillations. Significant increases
      in tumor size were also noted for the saline-treated groups, although this was
      not linked with the PCNA labeling index. CONCLUSIONS: The results indicate that
      saline is a promoter of urinary bladder carcinogenesis either because of the
      catheterization or the fluid itself.

PMID- 11972647
TI  - Surface antigen expression on bladder tumor cells induced by bacillus Calmette
      Guerin (BCG): A role of BCG internalization into tumor cells.
AB  - BACKGROUND: The antitumor mechanisms of bacillus Calmette-Guerin (BCG) against
      bladder cancer is still unclear. We previously reported that BCG was internalized
      by and survived within murine bladder tumor cells (MBT-2) for at least 40 days.
      In the present study, we investigated the effect of BCG on the surface antigen
      expression of bladder tumor cells and the characteristics of these cells as
      antigen-presenting cells in vitro. METHODS: Surface antigen (major
      histocompatibility complex (MHC) Class II, CD1, CD80 and intercellular adhesion
      molecule-1 (ICAM-1)) expression on BCG-treated murine (MBT-2) and human (T-24,
      J82) bladder tumor cells were analyzed using flow cytometry. The production of
      interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) from murine lymphocytes
      sensitized with BCG or BCG-treated tumor cells were also investigated. RESULTS:
      The expressions of MHC Class II, CD1, CD80 and ICAM-1 were augmented in all of
      the bladder tumor cell lines used; however, they were augmented to varying
      degrees among the cell lines that were treated with live BCG. Heat-killed BCG had
      little or no effect. When murine lymph node cells sensitized with BCG or BCG
      treated MBT-2 cells were cocultured with BCG-treated MBT-2 cells, significant
      amounts of IL-2 and IFN-gamma were produced in the culture medium. CONCLUSIONS:
      BCG induced the augmented expression of surface antigens, such as MHC Class II,
      CD1, CD80 and ICAM-1, of bladder tumor cells. Furthermore, BCG-treated MBT-2
      cells could stimulate BCG-sensitized lymphocytes to produce IL-2 and IFN-gamma.
      These results strongly suggest that bladder tumor cells gained the
      characteristics and functions of antigen-presenting cells (APC).

PMID- 11972648
TI  - Changes in extent and zonal distribution of prostatic adenocarcinoma in patients
      preoperatively treated with neoadjuvant endocrine therapy: analysis on whole
      mounted prostatectomy specimens.
AB  - BACKGROUND: An increasing number of pharmacologic agents that induce reversible
      androgen deprivation are available for neoadjuvant endocrine therapy (NET) for
      prostatic adenocarcinoma (PCA). If information about the regression pattern of
      PCA after NET is recognized, more effective decision-making for subsequent
      therapies such as prostatectomy and radiotherapy, will be possible. METHODS: The
      extent and zonal distribution of PCA with or without NET were examined in totally
      embedded radical prostatectomy specimens obtained from 103 patients with PCA.
      Seventy-nine of the 103 patients received androgen deprivation therapy
      (castrated). The zonal location of PCA lesions (non-transition vs transition
      zone), was identified in three slices from the inferior, middle and superior
      parts of the prostate. The area of the PCA lesions in these zones was measured.
      RESULTS: Prostatic adenocarcinoma was identified in 94 of 103 cases: 24 of 24
      cases (100%) and 70 of 79 cases (87%) in the non-castrated and castrated groups,
      respectively. The NET induced a mean of 21% reduction of the prostate volume and
      lowered the serum PSA level by one eighth. The frequency of capsular penetration
      in the castrated cases (57%) was lower than in the non-castrated cases (83%) and
      confinement of the PCA lesion was found in 32% of the castrated and 17% of the
      non-castrated cases. The reduction rate of the extent of the PCA lesions in the
      non-transition and transition zone was 33% and 28%, respectively. The extent of
      the PCA lesions were smaller in the anterior parts, especially at the superior
      portion of the prostate. CONCLUSION: Neoadjuvant endocrine therapy induced
      involutional changes of the PCA evenly across both the non-transition and
      transition zones. The density of the PCA lesions was low in the anterior part of
      the prostate. This information is useful for decision-making in post-NET.

PMID- 11972649
TI  - Clinical utility of ursodeoxycholic acid in preventing flutamide-induced
      hepatopathy in patients with prostate cancer: a preliminary study.
AB  - BACKGROUND: The present study was designed to ascertain retrospectively the
      validity of ursodeoxycholic acid (UDCA) in the treatment of prostate cancer in
      terms of prophylactic effects on the occurrence of flutamide-induced hepatopathy
      in a large number of patients surveyed in a multi-center cooperative study.
      METHODS: One hundred and eighty-one patients (74.1 +/- 4.9 years) with prostate
      cancer treated with flutamide with (n = 70) or without (n = 111) UDCA were
      retrospectively evaluated and the occurrence of hepatopathy was compared between
      these two patient groups. RESULTS: Between patients treated with UDCA and those
      without it, no significant differences were noted in age, clinical stage, grade,
      duration of flutamide administration and serum prostate-specific antigen (PSA)
      levels before treatment. However, there were significant differences in the
      presence or absence of previous treatments and treatments used together with
      flutamide. The incidence of hepatopathy was 11.4% (8/70) in patients with UDCA
      and 32.4% (36/111) in those without it, showing a statistically significant
      difference (P < 0.05). The hepatopathy-free rate obtained by the Kaplan-Meier
      method was also significantly higher in patients with UDCA (88.4% 1 year
      following flutamide administration) than that in those without it (59.6%) (P <
      0.005). CONCLUSION: These results suggest that UDCA has a prophylactic effect
      against flutamide-induced hepatopathy in patients with prostate cancer.

PMID- 11972650
TI  - Preoperative predictors of cancerous involvement of the neurovascular bundles in
      patients with localized prostate cancer.
AB  - BACKGROUND: The purpose of this study was to identify preoperative variables that
      would be useful in objectively selecting prostate cancer patients for nerve
      sparing prostatectomy. METHODS: Twenty-six patients with clinical T1c-T2c cancers
      were evaluated for cancerous involvement in the region of the neurovascular
      bundles (NVB) from prostatectomy specimens. Preoperative prostate-specific
      antigen (PSA) and pathologic features in systematic biopsy specimens also were
      reviewed. RESULTS: A total of eight (31%) patients had cancerous involvement in
      the region of the NVB, including four on the right side, three on the left side
      and one on both sides. The percentage of each biopsy specimen occupied by the
      cancer was scored from zero to four and defined as the positive biopsy score.
      Preoperative PSA (P = 0.046), mean positive biopsy score (total sum of positive
      biopsy score divided by number of biopsy specimens; P = 0.001), number of cores
      containing cancer (P = 0.011), percentage of cores involved (P = 0.036) and
      maximum positive biopsy score (P < 0.001) were significant for predicting
      cancerous involvement in the NVB region using univariate analysis. However, only
      the mean positive biopsy score was independently significant according to
      multivariate analysis. To predict cancerous involvement in the region of each
      NVB, we found that ipsilateral mean positive biopsy score (total sum of
      corresponding positive biopsy score divided by number of ipsilateral biopsy
      specimens), number of cores involved on the ipsilateral side, percentage of cores
      involved on the ipsilateral side and maximum positive biopsy score on the
      ipsilateral side were significant predictive variables: the ipsilateral mean
      positive biopsy score being most appropriate for clinical practice. CONCLUSION:
      Ipsilateral mean positive biopsy score in systematic biopsy specimens can be an
      appropriate variable for selecting patients with localized prostate cancer for
      nerve-sparing prostatectomy.

PMID- 11972651
TI  - Adrenal leiomyosarcoma extending into the right atrium.
AB  - Primary soft tissue sarcoma of the adrenal gland is very rare and aggressive. In
      right adrenal tumors, because of direct venous drainage into inferior vena cava,
      the tumor may invade the vena caval wall toward the right atrium. We present a
      case of adrenal leiomyosarcoma extending into the right atrium.

PMID- 11972652
TI  - Intracavitary administration of OK-432 with subcutaneous priming for malignant
      ascites in a case of advanced renal cell carcinoma.
AB  - The intracavitary injection of OK-432 (a streptococcal preparation) with
      subcutaneous priming has been shown to be an effective immunotherapy for patients
      with malignant effusion. We applied this treatment in a case of advanced renal
      cell carcinoma with massive ascites. The patient received 0.2 Klinishe Einheit
      (KE) OK-432 in the subcutaneous injection twice (day 1 and day 7) followed by
      10KE OK-432 intra-abdominal administration (day 9). The treatment was performed
      safely without major side-effects except for transient pyrexia. A significant
      reduction of ascites was noted 1 month after the treatment without subsequent re
      accumulation. Intracavitary injection of OK-432 with subcutaneous priming seems
      to be a simple, safe and effective treatment for ascites in advanced renal cell
      carcinoma.

PMID- 11972653
TI  - Retroperitoneoscopic ureterocutaneostomy for obstructive uropathy with advanced
      bladder cancer: a case report.
AB  - A 71-year-old man who had previously undergone left nephroureterectomy for renal
      pelvic tumor developed advanced bladder cancer with obstructive uropathy. He
      complained of severe macroscopic hematuria, dysuria and presented with postrenal
      failure. To rescue the renal function and improve ease the patient's symptoms,
      retroperitoneoscopic ureterocutaneostomy was performed. The operation time was 90
      min and blood loss was kept to a minimum. He was able to walk and eat on the
      first postoperative day, and he left the hospital on postoperative day 21 with
      satisfactory renal function. Retroperitoneoscopic ureterocutaneostomy is simple,
      less invasive and a reproducible procedure for poor prognostic advanced cancer
      patients with obstructive uropathy.

PMID- 11972654
TI  - Renal dysplasia associated with ureteral ectopia and ipsilateral seminal vesicle
      cyst.
AB  - The simultaneous presence of renal aplasia/dysplasia, ureteral ectopia and
      seminal vesicle cyst represents an exceptionally rare malformation. The
      literature is reviewed here and a new case of such malformation, concerning a 45
      year-old man affected by recurrent epididymitis, is reported.

PMID- 11972656
TI  - Tool boxes.

PMID- 11972655
TI  - Testicular cancers occurring in brothers with cryptorchism.
AB  - We report a case of familial testicular cancer associated with undescended testes
      in two brothers. The older brother (49 years) presented with a testicular tumor
      located in the right inguinal canal. The pathologic diagnosis was pure seminoma.
      Computerized tomography revealed iliac and retroperitoneal lymph node metastases.
      Four years later, the younger brother (44 years) developed bilateral testicular
      tumors, one located in the inguinal canal, the other located in the pelvic
      cavity. The pathologic diagnosis of both tumors was pure seminoma. Radiological
      examination revealed retroperitoneal lymph node metastases. Both patients
      received cisplatin-based combination chemotherapy as the initial treatment. The
      older brother suffered from repeated recurrences with lymph node metastases in
      the iliac and inguinal regions, but he was successfully treated with high-dose
      chemotherapy. The younger brother achieved long-term remission after
      retroperitoneal lymph node dissection following initial chemotherapy. We briefly
      review the reported cases of familial testicular cancer and discuss the
      association of the maldescent of the testes and familial testicular cancer cases.

PMID- 11972658
TI  - Cardiovascular health and physical activity in older adults: an integrative
      review of research methodology and results.
AB  - PURPOSE OF THE PAPER: The purpose of this article is to review the literature on
      physical activity and its relationship to cardiovascular risk factors and
      mortality in older adults, in an effort to clarify the specific benefits and
      optimal level of physical activity for cardiovascular health in the older adult
      population. BACKGROUND/RATIONALE: Despite physical activity being recognized as
      an important factor in the quality of life of older adults, there is a lack of
      clarity about the optimal level of physical activity that results in positive
      cardiovascular health benefits. DESIGN/METHODS: An integrative review of the
      literature using the MEDLINE and CINAHL databases from 1990 through August 2000
      was conducted identifying articles related to physical activity and cardiac risk
      factors, cardiovascular health, or mortality in the older adult.
      RESULTS/FINDINGS: Forty-four research articles were reviewed. The intervention
      studies generally provided support for positive cardiovascular changes with
      exercise, but the results were inconsistent, sample sizes were small, and the
      outcomes, interventions, and measures of physical activity differed between
      studies. There was wide variation in the method of measurement of physical
      activity in the studies. Studies showed an increase in mortality in those who had
      a sedentary lifestyle compared to those who were more physically active. Results
      were mixed related to plasma lipids levels. Three studies showed a positive
      effect of physical activity on blood pressure (BP), while three studies showed no
      relationship. Each of the studies that evaluated the relationship between
      physical activity and pulse rate showed a decreased rate with increased physical
      activity. CONCLUSIONS: The quantity and type of physical activity that should be
      recommended to bring about positive effects on cardiovascular health and
      mortality is unclear. There is support, however, that an active lifestyle
      decreases mortality. There is conflicting evidence to support positive effects of
      physical activity on cardiac risk factors. Further research is needed with larger
      sample sizes, better control of extraneous variables, and using measurements of
      physical activity that have undergone adequate psychometric testing.

PMID- 11972660
TI  - Patient and carer needs following a cancer-related hospital admission: the
      importance of referral to the district nursing service.
AB  - BACKGROUND: Despite 30 years of research attention, discharge planning and
      district nurse (DN) referral remain problematic and few cancer-related
      publications exist. With shorter hospitalizations, discharged cancer patients and
      their carers may experience unmet needs for assessment, information and support.
      Although DN referral might enable patient/carer needs to be met, the DN role
      lacks clarity. AIM: To investigate the needs of people with cancer, and their lay
      carers during discharge from hospital to home, and identify the role of DNs in
      meeting these needs. METHOD: In this qualitative study, 71 pre- and postdischarge
      interviews were performed with cancer patients and (where possible) their carers.
      Predischarge interviews focused on expectations and postdischarge interviews on
      experiences of discharge and aftercare. Interview tapes were transcribed and
      analysed thematically. RESULTS: Interviewees anticipated few aftercare needs
      during predischarge interviews but described met and unmet needs during
      postdischarge interviews. Unmet needs of those referred and not referred to the
      district nursing service were similar. Patients and carers had unmet needs for
      psychological support related to nutrition. Carers, especially those not resident
      with and not related to patients, had informational needs. Even very elderly, ill
      and isolated patients felt that other people had greater needs than their own and
      many thought that DNs only performed physical tasks. CONCLUSION: All cancer
      patients discharged from hospital might be referred to a DN for ongoing
      assessment of needs. However, to ensure optimal results, the DN role needs to be
      clarified and public perceptions altered. Further research on psychological
      aspects of nutrition and the needs of carers not resident with/not related to
      patients is necessary.

PMID- 11972659
TI  - Deliberate self-harm in adolescence: a systematic review of psychological and
      psychosocial factors.
AB  - AIMS: This paper is a systematic review of the research literature that
      identifies psychological and psychosocial factors associated with adolescent
      deliberate self-harm (DSH). The aims of this review were to identify the key
      psychological and psychosocial factors that aid the identification of individuals
      at risk of DSH, and suggest specific strategies for intervention. BACKGROUND:
      Research has highlighted a parallel rise in rates of DSH referrals to general
      hospitals and rates of successful suicides in the younger age groups and gender
      groups. It is also highlighted that pressure on services in responding to these
      increases may be resulting in an inadequate response to both first-episode DSH
      and repetition of self-harm. One cause for concern is the lack of adequate
      psychosocial assessment for adolescents presenting at hospital following a DSH
      incident. Research of the literature suggests that there may be a paucity of
      research into after-care strategies in self-harm to prevent repetition and
      escalation of self-destructive behaviour. METHODS: A systematic review of the
      literature was conducted to identify the psychological and psychosocial factors
      relating to DSH. Results. The results found typical psychological and
      psychosocial factors associated with DSH in adolescents, although psychosocial
      factors were less consistently measured because of the breadth of tools and
      methods used. CONCLUSIONS: It is discussed whether associated factors are
      causative of DSH or the accompanying symptoms in DSH. It is suggested that
      positive psychosocial factors may have a part to play in providing protection
      against DSH behaviour. Therapeutic responses to DSH are suggested as preventative
      measures against repeat episodes.

PMID- 11972661
TI  - Adolescent subjective well-being and realized values.
AB  - AIMS OF THE STUDY: The purpose of this study was to describe adolescent
      subjective well-being and realized values, and to examine the relationships
      between socio-demographic variables, realized values and subjective well-being
      from the adolescent perspective. RATIONALE: Adolescent subjective well-being was
      conceptualized by means of four different dimensions: satisfaction, ill-being,
      knowledge and activities related to well-being. The values were operationalized
      by eight core ideas from which a principal components analysis identified 10
      factors representing the realized values. DESIGN: Data were gained by self-report
      questionnaires from 245 adolescents from 7th and 9th grades, with a mean age of
      14 years, in 13 secondary schools in southern Finland. The data were analysed
      statistically. FINDINGS: According to the findings, most of the respondents were
      satisfied with life. However, one out of 10 did not experience the joy of life.
      There was no statistically significant difference in global satisfaction between
      girls and boys. Total ill-being among the adolescents was rare, but one out of
      four participants had fairly often worried about money and 17% were frequently
      unusually tired. Girls and pupils from the 9th class experienced more ill-being
      than boys and pupils from the 7th class. The findings suggest that certain values
      such as personal equilibrium, safe family relations, and family type are
      predictors of adolescent global subjective well-being. CONCLUSIONS: While
      assessing and promoting adolescent well-being it is important to pay special
      attention to the realization of values in life and not merely to appreciation of
      things. Implications for practice include the need to create opportunities for
      the realization of values when adolescents require health care services.

PMID- 11972662
TI  - Synergy towards health: a nursing intervention model for women living with
      fibromyalgia, and their spouses.
AB  - AIM: The purpose of this study was to develop a consensus-based nursing
      intervention model for women living with fibromyalgia, their spouses and nurses
      working in a community health centre in Quebec, Canada. BACKGROUND: Fibromyalgia
      syndrome, a rheumatic disorder associated with severe chronic pain and fatigue,
      has a major impact on the lives of individuals and their family. To date,
      research results on effective interventions are somewhat limited and
      inconclusive. Few studies take into account the perspective of those who live
      with this health problem on a day-to-day basis. METHODS: Data were collected
      mainly in 1999, through in-depth interviews and through group meetings using a
      qualitative research design, along the lines of the constructivist paradigm. The
      analysis plan aims for movement between the global and the specific: synthesis
      and thematic analysis. Analysed data were submitted to all participants
      throughout the data-collection process, thus allowing for shared constructions.
      FINDINGS: Results present the general consensus stemming from shared construction
      in all three groups. The nature of the intervention involves two major elements,
      support and teaching along with the fundamental importance of believing in the
      person. The timing of the intervention and the health and social context in which
      the intervention occurs also emerge as integral parts of the model. Synergy
      towards health in fibromyalgia emerges as the constitutive pattern composed of
      the following three elements: personal growth, spousal and professional support.
      The discussion addresses the model's components and uses an ecological
      perspective, in order to consider all the contexts that greatly influence the
      intervention. Empowerment is embedded in this intervention model. CONCLUSIONS:
      This study shows that research based on partnership allows the integration of
      perspectives and skills of various actors so as to develop meaningful
      interventions for both those seeking care and health professionals.

PMID- 11972663
TI  - Power dressing and meta-analysis: incorporating power analysis into meta
      analysis.
AB  - AIMS: This paper highlights the lack of consideration that is given to power in
      the health and social sciences, which is a continuing problem with both single
      study research and more importantly for meta-analysis. BACKGROUND: The power of a
      study is the probability that it will lead to a statistically significant result.
      By ignoring power the single study researcher makes it difficult to get negative
      results published and therefore affects meta-analysis through publication bias.
      Researchers using meta-analysis, who also ignore power, then compound the problem
      by including studies with low power that are more likely to show significant
      effects. METHOD: A simple means of calculating an easily understood measure of
      effect size from a contingency table is demonstrated in this paper. A computer
      programme for determining the power of a study is recommended and a method of
      reflecting the adequacy of the power of the studies in a meta-analysis is
      suggested. An example of this calculation from a meta-analytic study on
      intravenous magnesium, which produced inaccurate results, is provided.
      CONCLUSION: It is demonstrated that incorporating power analysis into this meta
      analysis would have prevented misleading conclusions being reached. Some
      suggestions are made for changes in the protocol of meta-analytic studies, which
      highlight the importance of power analysis.

PMID- 11972666
TI  - Response to: 'The nature of philosophy of science, theory and knowledge relating
      to nursing and professionalism' by J.E. Rutty, Journal of Advanced Nursing (1998)
      28, pp. 243-250.

PMID- 11972668
TI  - Response to: 'Private thoughts in public spheres: issues in reflection and
      reflective practices in nursing' by A.H. Cotton. Journal of Advanced Nursing,
      (2001) 36, 512-519.

PMID- 11972669
TI  - Learning preferences of paediatric intensive care nurses.
AB  - AIM: This paper reports the views of students on the teaching and learning
      strategies used in paediatric intensive care nursing courses. STUDY METHODS:
      Qualitative methods of data collection and analysis were used. A case study of
      one paediatric intensive care nursing course was carried out, followed by group
      interviews with students from a further seven courses. Local ethics committee
      protocols were followed. Data were analysed using constant comparative analysis.
      STUDY FINDINGS: Qualified nurses undertaking paediatric intensive care nursing
      courses seek a specific knowledge base, relevant to their clinical practice.
      Their preferred way of learning in this situation is teaching by knowledgeable
      experts who are also prepared to discuss issues that arise. Although in some
      instances student centred or self-directed approaches were considered acceptable,
      Students still require clear guidance and structure in their learning. Students
      did not summarily oppose student centred approaches to teaching and learning,
      however, time considerations and whether this would reduce the amount of study
      time provided by their employers were important factors. There was evidence that
      students do not necessarily have one specific learning preference. LIMITATIONS:
      This study explored only paediatric intensive care nurse education, and was not
      intended to be generalizable beyond this field. CONCLUSION: The findings from
      this study indicate that no single educational approach is universally seen as
      the most attractive for PICU nurses. The major considerations in designing and
      implementing PICU nursing courses should be that content is clearly rated to the
      clinical speciality, theory is clearly linked to practice, and that the time
      constraints for students who are additionally in full time employment are taken
      into account.

PMID- 11972670
TI  - Nursing education in Norway.
AB  - AIM: The aim of this paper is to describe nursing education in Norway and some
      essential questions and challenges regarding the undergraduate and newly
      graduated nurses' competencies and functionally preparedness. BACKGROUND: The
      first formal training of nurses in Norway started in Oslo in 1886. Since then the
      education has changed considerably. As long as society is changing, and nurses
      are going to meet and adapt to societies needs, the education of nurses will also
      have to change continuously. The present general plan of nursing education has
      gone through a long process. The discussions have concerned the content of
      medical and natural science subjects, the practical part of the training and the
      relation between theory and practice. CHALLENGES: There are challenges in nursing
      education in Norway today. We have seen that recruitment has decreased, and that
      nurses seek jobs where they are better paid. To increase the accessibility
      distance and part-time education has been established. The theory-practice gap
      will always exist. Therefore we should aim to prepare the students to minimize
      this gap in a way that they can combine training of nursing with training in
      improvement. The demand of a masters degree to be a nursing teacher has reduced
      the teachers' ability to keep up their practical skills. The government pays
      nursing teachers who want to practice as nurses for several months to maintain
      their salary level during that period. CONCLUSIONS: There are many possibilities
      to improve nursing education in Norway. We are on our way with highly qualified
      teachers and students, and we still have enough good applicants. The new general
      plan and new law for universities and university colleges offer great
      opportunities. However, the shortage of nurses is a great challenge for further
      quality improvement both in clinical practice and in education.

PMID- 11972671
TI  - The beliefs of nurses who were involved in a whistleblowing event.
AB  - BACKGROUND: Nursing codes of ethics bind nurses to the role of patient advocate
      and compel them to take action when the rights or safety of a patient are
      jeopardized. Reporting misconduct is known as whistleblowing and studies indicate
      that there are personal and professional risks involved in blowing the whistle.
      AIM: The aim of this study was to explore the beliefs of nurses who wrestled with
      this ethical dilemma. DESIGN: A descriptive survey design was used to examine the
      beliefs of nurses in Western Australia who reported misconduct (whistleblowers)
      and of those who did not report misconduct (nonwhistleblowers). METHODS: The
      instrument listed statements from current ethical codes, statements from
      traditional views on nursing and statements of beliefs related to the
      participant's whistleblowing experience. Respondents were asked to rate each item
      on a five-point Likert format which ranged from strongly agree to strongly
      disagree. Data were analysed using a Pearson's correlation matrix and one-way
      ANOVA. To further explore the data, a factor analysis was run with varimax
      rotation. RESULTS: Results indicated that whistleblowers supported the beliefs
      inherent in patient advocacy, while nonwhistleblowers retained a belief in the
      traditional role of nursing. Participants who reported misconduct
      (whistleblowers) supported the belief that nurses were primarily responsible to
      the patient and should protect a patient from incompetent or unethical people.
      Participants who did not report misconduct (nonwhistleblowers) supported the
      belief that nurses are obligated to follow a physician's order at all times and
      that nurses are equally responsible to the patient, the physician and the
      employer. CONCLUSION: These findings indicate that nurses may respond to ethical
      dilemmas based on different belief systems.

PMID- 11972672
TI  - 'Great fleas have little fleas': Irish student midwives' views of the hierarchy
      in midwifery.
AB  - BACKGROUND: Many studies have investigated the world of the student nurse, but
      there is little work into the lives and experiences of student midwives. Studies
      of Irish midwives' provision of care have demonstrated that they are not
      fulfilling their complete role, and research into their education was deemed to
      be necessary. AIM: To explore the opinions, feelings and views of student
      midwives as they progressed through their 2-year education programme in Ireland.
      METHODS: Both quantitative and qualitative methods were used and the qualitative
      sections of the study were guided by the phenomenological approach. Ethical
      approval was granted. All students in the first intake of 1995 in all seven
      midwifery schools in Southern Ireland agreed to take part (n=125). Individual and
      group interviews, diary-keeping and questionnaires collected data. RESULTS: The
      findings presented in this paper describe the students' views of the hierarchical
      structures in midwifery, and the role and behaviours of the 'Matron'. The data
      describes a subculture of nursing/midwifery subordination. DISCUSSION: One reason
      for the hierarchical nature of the midwifery profession may be because it is an
      almost totally female-dominated profession, with the female hierarchy exercising
      control over other women within a male-based power structure. Many hospitals
      preferred to employ their own students as staff, ensuring a continuation of the
      hierarchical regime. CONCLUSION: The recurring nature of this problem may be
      because midwives now fear change more than they desire it. Further research is
      required to ascertain whether the reason for the strong hierarchy is because of
      the continuation of midwifery from the male-dominated profession of nursing, to
      the existence of the industrial/economic model of maternity care or to the impact
      of the medicalization of childbirth.

PMID- 11972674
TI  - Effects of different fibre sources and fat addition on cholesterol and
      cholesterol-related lipids in blood serum, bile and body tissues of growing pigs.
AB  - Knowledge is limited on the efficacy of hindgut-fermentable dietary fibre to
      reduce blood, bile and body tissue cholesterol levels. In three experiments with
      growing pigs the effects of different kinds and levels of bacterially fermentable
      fibre (BFS) on cholesterol metabolism were examined. Various diets calculated to
      have similar contents of metabolizable energy were supplied for complete
      fattening periods. In the first experiment, a stepwise increase from 12 to 20%
      BFS was performed by supplementing diets with fermentable fibre from sugar beet
      pulp (modelling hemicelluloses and pectin). Beet pulp, rye bran (modelling
      cellulose) and citrus pulp (pectin) were offered either independently or in a
      mixture in the second experiment. These diets were opposed to rations
      characterized in carbohydrate type by starch either mostly non-resistant
      (cassava) or partly resistant (maize) to small intestinal digestion. The third
      experiment was planned to explore the interactions of BFS from citrus pulp with
      fat either through additional coconut oil/palm kernel oil blend or full-fat
      soybeans. In all experiments the increase of the BFS content was associated with
      a constant (cellulose) or decreasing (hemicelluloses, pectin) dietary proportion
      of non-digestible fibre. In experiment 1 an inverse dose-response relationship
      between BFS content and cholesterol in blood serum and adipose tissue as well as
      bile acid concentration in bile was noted while muscle cholesterol did not
      respond. In experiment 2 the ingredients characterized by cellulose and
      hemicelluloses/pectin reduced cholesterol-related traits relative to the low-BFS
      high-starch controls whereas, except in adipose tissue cholesterol content, the
      pectinous ingredient had the opposite effect. However, the changes in serum
      cholesterol mainly affected HDL and not LDL cholesterol. Adipose tissue
      cholesterol also was slightly lower with partly resistant starch compared to non
      resistant starch in the diet. Experiment 3 showed that the use of citrus pulp
      increased serum cholesterol concentrations when levels were low in the
      corresponding low-BFS diets (low-fat and soy bean diets), but caused no further
      increase in the coconut-oil/palm kernel oil blend diet. From the present results
      it seems that fermentable hemicelluloses have a more favourable effect of
      decreasing metabolic cholesterol and related traits than hardly digestible fibre,
      fermentable cellulose or, particularly, pectin. Furthermore, some types of fibre
      expressed a certain potential to reduce cholesterol content of fat pork and pork
      products by up to 10% (experiment 1) and 25% (experiment 2).

PMID- 11972675
TI  - Selenium supplementation and selenium status of dairy cows fed diets based on
      grass, grass silage or maize silage.
AB  - In three separate trial series (TS) the effect of diet composition on selenium
      (Se) status of dairy cows were investigated. Diets were formulated based mainly
      on grass (TS1), grass silage (TS2) or maize silage (TS3) with different levels of
      Se supplementation. Each TS comprised a total of 30 dairy cows and contained one
      treatment group without Se supplementation (control) and two groups with
      increasing levels of Se supplementation (levels 1 and 2). Selenium was
      administered as Na-selenite. The control groups of the different TS showed a very
      low Se supply of 38-54 microg Se/kg DM. At level 1 the Se supply was increased to
      102-165 microg Se/kg DM and at level 2 was 294-373 microg Se/kg DM. After
      completion of the 6-week trials the average plasma Se concentration of the
      control cows (without Se supplementation) across all TS was 21.5 microg/l; this
      increased significantly following Se supplementation, to 37.7 microg/l at level 1
      and 61.5 microg/l at level 2. The plasma glutathione peroxidase (GSH-Px) activity
      of the control cows averaged 67 U/l, rising considerably after supplementation at
      level 1 to a value of 101 U/l, but showed little further increase at level 2 with
      a mean value of 120 U/l. By contrast, the average Se content of the milk was
      unchanged in the control and level 1 groups at 10.5 microg/kg and 10.9 microg/kg,
      respectively, and only increased markedly after supplementation at level 2 to a
      mean value of 15.1 microg/kg. The diet based on maize silage, while having a
      similar Se content as the grass and grass silage-based diets, resulted in a
      slightly improved Se status, which is due to a higher Se intake from soybean
      meal.

PMID- 11972676
TI  - The assessment of the frequency of chews during rumination enables an estimation
      of rumination activity in hay-fed sheep.
AB  - The objective was to assess rumination behaviour and, more specifically, the
      intra-individual and inter-individual variation of the frequency of chews during
      rumination (per min) in five Blackhead sheep fed hay at a level of 100%
      maintenance (experimental period [EP] I), 50% maintenance (EP II) and ad libitum
      (EP III). Animals ruminated in EP II less (416 min/day) than in EP I and III (558
      and 592 min/day, respectively). Mean inter-individual coefficients of variation
      (CV) of frequency (defined as number of chews/duration of chewing per cycle) were
      12.5%, mean intra-individual CV were 2.5%. The respective CVs for the duration of
      rumination per day were 8.1 and 9.7%, respectively. The level of intake
      influenced the frequency of chews significantly. It is concluded that the
      frequency of chews has to be considered in studies investigating chewing
      behaviour of ruminants. Under the experimental conditions investigated, number of
      chews during rumination per day could be estimated by the frequency of chewing
      with nearly the same precision as by using the duration of rumination per day.

PMID- 11972677
TI  - Gustatory responses of pigs to sixty compounds tasting sweet to humans.
AB  - The gustatory responses of pigs to 60 compounds perceived as sweet by humans were
      studied via a semi-quantitative behavioural method derived from the Richter two
      bottle preference test. Among the 60 compounds tested 35 are effective in pigs,
      but with an effectiveness much lower in pigs than in humans. Lugduname and
      carrelame, which are the two most potent sweeteners in humans, are also the most
      effective compounds in pigs.

PMID- 11972679
TI  - Effect of acetic acid consumption on clinical laboratory values in the dog.
AB  - To investigate the influence of food enriched with acetic acid on the clinical,
      biochemical, electrolyte, blood gas, haematological and urinary variables in the
      dog, a cross-over study was carried out with periods of approximately 2 weeks
      involving six healthy, adult dogs. Another objective was to determine the maximum
      concentration of acetic acid that the dogs found to be palatable. The dogs were
      maintained on a commercial meat-based food with added acetic acid and/or glucose.
      The administered acetic acid was increased in stages. All dogs accepted the diet
      containing acetic acid at a level of 5% of metabolizable energy. Except for a
      decrease in plasma total protein, none of the variables were significantly
      affected by acetic acid consumption. Acetic acid feeding did not affect plasma
      acetate concentration and urinary acetate excretion, indicating that dogs
      efficiently metabolize ingested acetic acid.

PMID- 11972678
TI  - Supplementation of algae to the diet of pigs: a new possibility to improve the
      iodine content in the meat.
AB  - Meat products with a higher iodine content can be produced through feeding
      animals with a diet supplemented with inorganic iodine salts or with algae
      containing high iodine. This may help to improve daily iodine intake and to
      control iodine deficiency disorders (IDD) in man. In the present study a total of
      40 crossbred pigs (Deutsche Landrasse x Pietrain) with an average body weight of
      17 kg were allotted to either a control group, to two groups receiving potassium
      iodide (KI) at different concentrations (5 or 8 mg iodine per kg of feed) or to
      two groups receiving the algae Laminaria digitata containing the same amount of
      iodine. After pigs were fed with iodine-supplemented diets for 3 months, it was
      found that compared to the control group the iodine content increased by up to
      45% in fresh muscle, by 213% in adipose tissue, by 124% in the heart, by 207% in
      the liver and by 127% in the kidneys. There was a significant (p < 0.01) higher
      concentration of serum thyroxine (T4) and a lower concentration of serum
      triiodothyronine (T3) in those iodine-supplemented groups. The iodine content of
      urine from all iodine-supplemented groups was also greatly increased.
      Furthermore, it was shown that the supplementation of algae into feed could
      increase daily body weight gain by 10% (p > 0.05). It is suggested that the carry
      over of iodine through feeding pigs with an algae-supplemented feed could be
      beneficial to both the control of IDD and the improvement of pig production.

PMID- 11972680
TI  - The plasma level of triacylglycerols in horses fed high-fat diets containing
      either soybean oil or palm oil.
AB  - The influence of dietary soybean oil versus palm oil on the plasma level of
      triacylglycerols was determined in a crossover experiment with four horses. Based
      on published data for humans and laboratory animals it was expected that a diet
      rich in unsaturated fatty acids in the form of soybean oil compared to saturated
      fatty acids in the form of palm oil would lower the plasma triacylglycerol level.
      The feeding of soybean oil versus palm oil for a period of four weeks did not
      change the level of plasma triacylglycerols in horses. Mean levels of
      triacylglycerol, free fatty acids and 3-hydroxybutyrate were 0.17 (SE, 0.04),
      0.44 (SE, 0.063) and 0.16 (SE, 0.008) mmol/l, respectively. The fatty acid
      composition of the plasma triacylglycerols reflected the fatty acid composition
      of the diets. The activity of lipoprotein lipase was not different between the
      treatments. It is concluded that, under the present experimental conditions, the
      feeding of soybean oil to horses does not affect triacylglycerol secretion into
      plasma and thus does not influence the concentration of plasma triacylgycerols,
      when compared to the feeding of palm oil.

PMID- 11972681
TI  - Influence of a conjugated linoleic acid mixture on growth, organ weights, carcass
      traits and meat quality in growing pigs.
AB  - Grain soybean meal diets, either with 2% of a conjugated linoleic acid (CLA)
      preparation or with 2% rapeseed oil (control), were tested in 2 x 40 pigs,
      Pietrain x (Landrace x Large White), each group with 20 female in the live weight
      range 23.5-117.0 kg and 20 male-castrated pigs in the live weight range 23.5
      110.6 kg. The CLA-content of the preparation amounted to 54.0% cis/trans +
      trans/cis, 8.7% cis/cis and 32.7% trans/trans isomers. Daily weight gain, feed
      intake and feed : gain ratio were not influenced by the diets tested. The carcass
      lean increased significantly from 57.2% of the control group to 58.7% in the CLA
      group (p < 0.05). The male-castrated showed a stronger CLA effect than the female
      pigs - not only was the carcass lean significantly increased by 2%, but backfat
      thickness was significantly decreased by 2.8 mm, i.e. minus 11% (as compared with
      barrows of the control). The meat of CLA-fed pigs had a higher conductivity. A
      CLA effect on further meat quality characteristics (pH 45 min post-mortem,
      impedance, colour criteria, intramuscular fat, drip loss, frying loss, shear
      force, sensory attributes) could not be detected. There were some significant
      correlations between the meat quality attributes.

PMID- 11972682
TI  - Influence of ciliate protozoa on biochemical changes and hydrolytic enzyme
      profile in the rumen ecosystem.
AB  - AIMS: To assess the effect of presence or absence of rumen protozoa on
      fermentation characteristics and enzyme profile in growing lambs. METHODS AND
      RESULTS: Weaner lambs (G1, G2, G3, G4, G5 and G6 groups) were defaunated by oral
      administration of sodium laurel sulphate (at 8 g 100 kg(-1) body weight). The
      lambs of G4, G5 and G6 groups were refaunated. The roughage and concentrate ratio
      in the diet of G1 and G4, G2 and G5, and G3 and G6 were 50:50 (R1), 65:35 (R2)
      and 80:20 (R3), respectively. Daily dry matter intake was similar in defaunated
      and faunated lambs. However, digestibility of organic matter (OM), cellulose and
      gross energy were lower in defaunated lambs while crude protein (CP)
      digestibility was similar in both defaunated and faunated lambs. The rumen pH and
      NH3-N were lower (P < 0.01) while TVFA, total-N and TCA-ppt-N were higher (P <
      0.01), in defaunated lambs. Ruminal activity of carboxymethyl cellulase was lower
      (P < 0.01) in defaunated lambs and amylase, xylanase, protease and urease were
      similar in faunated and defaunated lambs. Nutrient utilization, rumen metabolites
      and ciliate protozoal count were higher, whereas digestibility of fibre fractions
      was lower in high rather than low concentrate fed lambs. The rumen protozoa
      present before defaunation were B-type and the protozoa which re-established on
      refaunation were also B-type. CONCLUSIONS: Absence of ciliate protozoa decreased
      nutrient digestibility and increased ruminal TVFA and total-N with lower NH3-N
      concentration, indicating better energy and protein utilization in defaunated
      lambs. SIGNIFICANCE AND IMPACT OF THE STUDY: Defaunation improved energy and
      protein utilization in lambs.

PMID- 11972683
TI  - Autolytic phenotype of Lactococcus lactis strains isolated from traditional
      Tunisian dairy products.
AB  - AIMS: To evaluate the autolytic properties of Lactococcus lactis strains isolated
      from artisan Tunisian dairy products, their peptidoglycan hydrolase content and
      their activity spectrum. METHODS AND RESULTS: The autolytic phenotype of
      Lactococcus strains was evaluated under starvation conditions in potassium
      phosphate buffer. The results obtained highlighted a high degree of diversity
      among the strains analysed, allowing the identification of high and low autolytic
      Lactococcus lactis strains. Peptidoglycan hydrolase content was evaluated by
      renaturing SDS-PAGE using cells of Micrococcus lysodeikticus as a target for the
      enzymatic activity. A major activity band migrating at about 45 kDa was observed.
      The lytic activity, evaluated in the presence of different chemicals, was
      retained in 8% NaCl, 15 mmol l(-1) CaCl2, and in a pH range between 5 and 9.5.
      The substrate specificity of peptidoglycan hydrolase from Lactococcus strains was
      evaluated in renaturing SDS-PAGE incorporating cells of different bacterial
      species. The major autolysin of Lactococcus lactis was active against cells of
      Lactococcus lactis subsp. lactis, Streptococcus thermophilus, Lactobacillus
      delbrueckii subsp. bulgaricus, Lactobacillus helveticus and Listeria
      monocytogenes. CONCLUSIONS: Autolytic activity is widely distributed in
      Lactococcus lactis and the rate of autolysis is strain-dependent. The major
      peptidoglycan hydrolase showed a wide spectrum of activity against several lactic
      acid bacteria and bacterial species involved in food-related infection.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The autolytic phenotype of Lactococcus
      lactis strains isolated from Tunisian artisan dairy products has been determined,
      and the data obtained should allow the selection of strains of technological
      interest in the cheese-ripening process.

PMID- 11972684
TI  - Differentiation and identification of Enterococcus durans, E. hirae and E.
      villorum.
AB  - AIMS: To compare different tests in the identification of Enterococcus durans, E.
      hirae and E. villorum strains. These bacteria belong to the E. faecium species
      group and are phylogenetically closely related, as evidenced by 16S rRNA sequence
      homologies of over 98.8%. METHODS AND RESULTS: Sodium dodecyl sulphate
      polyacrylamide gel electrophoresis analysis of whole-cell protein, tRNA
      interpacer polymerase chain reaction (PCR) and arbitrarily-primed (D11344-primed
      AP) -PCR analysis correctly identified all three species in a collection of
      strains from very diverse origins. In contrast, biochemical reactions only
      allowed the unequivocal differentiation of the three species as a group from the
      other enterococci. Within this group, D-xylose acidification can be used to
      differentiate E. villorum, but exceptions occur. Strains highly susceptible to
      clindamycin can be identified as E. durans, but many strains of this species
      cannot be differentiated from E. hirae and E. villorum due to acquired
      resistance. CONCLUSIONS: Despite their close relationship, E. durans, E. hirae
      and E. villorum can be differentiated by genomic methods and by whole-cell
      protein analysis. SIGNIFICANCE AND IMPACT OF THE STUDY: Only a minority of
      strains of these three enterococcal species can be identified reliably by the
      currently available and commonly applied phenotypic tests.

PMID- 11972685
TI  - Microbial quality of wastewater: detection of hepatitis A virus by reverse
      transcriptase-polymerase chain reaction.
AB  - AIMS: The persistent circulation of hepatitis A virus (HAV) in the Mediterranean
      area suggests the need for monitoring its presence in the environment. A reverse
      transcriptase-polymerase chain reaction (RT-PCR) was used to detect the presence
      of HAV in several consecutive raw sewage and final effluent samples, collected
      over an 8-month period from an activated sludge treatment plant in southern
      Italy. METHODS AND RESULTS: Two distinct purification protocols, either based on
      antigen-capture with monoclonal antibody (AC) or RNA extraction, were compared.
      The possible influence of the antibody used in the AC phase was evaluated in
      preliminary experiments on HAV-spiked samples, using two different monoclonal
      antibodies. Hepatitis A virus RNA was detected in all but one sewage
      environmental sample examined. The contemporary presence of enteroviruses,
      reoviruses and phages was observed, while HAV growth in cell culture was
      hampered. CONCLUSIONS: The RT-PCR technique was confirmed to be a valuable tool
      for the rapid monitoring of HAV in sewage samples. In addition, this study
      demonstrated that application of different sample purification methods can result
      in different levels of sensitivity of the assay and that, in the antigen-capture
      method, the choice of antibody can have a crucial role. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This work underlines the need for technical uniformity in
      environmental studies from different laboratories for a correct and useful
      comparison of the results.

PMID- 11972686
TI  - Diversity of chromium-resistant and -reducing bacteria in a chromium-contaminated
      activated sludge.
AB  - AIMS: This study attempts to establish a relationship between the Cr(VI)
      resistance of the culturable microbial community and the Cr(VI) resistance and
      Cr(VI)-reducing ability of representative strains of each population, in order to
      assess whether these are exclusive characteristics of one microbial group or
      abilities shared among many groups. METHODS AND RESULTS: A group of 48 Cr(VI)
      resistant isolates, with different colony types, was isolated from chromium
      contaminated activated sludge. Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis protein patterns and fatty acid methyl ester analysis identified
      six populations, representing 54% of the isolated bacteria, as belonging to the
      genera Acinetobacter and Ochrobactrum. The remaining populations included strains
      identified as species of the beta-Proteobacteria and high G + C Gram-positive
      bacteria. The Cr(VI) resistance and reduction ability of the strains were tested.
      All but two isolates grew in the presence of 1 mmol l(-1) Cr(VI). During
      enrichment, all isolates were able to survive to 2 mmol l(-1) Cr(VI) and complete
      Cr(VI) reduction was achieved. Representative strains of each population were
      able to partially reduce (5.4-39.1%) the Cr(VI) present in the growth medium.
      CONCLUSIONS: Most of the identified isolates have never been reported to be
      Cr(VI)-resistant and/or Cr(VI)-reducing strains. The mechanisms of Cr(VI)
      resistance and reduction may differ from group to group; therefore, it is evident
      that both Cr(VI) resistance and reduction are shared abilities and not an
      exclusive characteristic of a single group, possibly reflecting horizontal
      genetic transfer resulting from selective pressure in this contaminated
      environment. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the
      first study of a microbial community under chronic chromate stress and, as the
      success of microbial-based metal remediation technologies requires a better
      understanding of the microbial community and the population response to metal
      stress, it may contribute to the implementation of a strategy of bioremediation
      of chromate-contaminated environments.

PMID- 11972687
TI  - The detection and recovery of Erysipelothrix spp. in meat and abattoir samples in
      Western Australia.
AB  - AIMS: To investigate the occurrence of Erysipelothrix rhusiopathiae and other
      Erysipelothrix spp. in abattoir and meat samples in Western Australia. METHODS
      AND RESULTS: Samples were collected from various parts of pig and sheep
      carcasses, as well as different sections of slaughtering line, pen soil and
      effluent. Previously evaluated culture methods were applied for the isolation of
      Erysipelothrix spp., in conjunction with phenotypic and genotypic detection and
      identification procedures. Of 109 samples from the two abattoirs, 35 (32.1%) were
      Erysipelothrix genus-specific PCR-positive. These came from swabs of animal
      exterior surfaces and joints, slaughtering areas, pig pen soil and abattoir
      effluent. Four samples (3.7%) from sheep arthritic joints and pig abattoir
      effluent were also E. rhusiopathiae species-specific PCR-positive. Of 123 carcass
      washing samples, 12 (9.8%) were genus-specific PCR-positive, and these came from
      all five kinds of meat samples tested, including beef, lamb, mutton, pork and
      chicken. Four of them (3.3%) were also species-specific PCR-positive. A total of
      25 isolates was recovered from the samples, of which seven were identified as E.
      rhusiopathiae, seven were consistent with E. tonsillarum, and the remaining 11
      were other species of Erysipelothrix. CONCLUSIONS: Erysipelothrix spp. can still
      be isolated and identified from specimens of animal origin with relative ease,
      provided that appropriate cultural and molecular procedures are used. Clinical
      microbiology laboratories may need to improve their diagnostic protocols.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms that E. rhusiopathiae
      and other species of Erysipelothrix continue to colonize and contaminate farmed
      animals and animal products. Erysipelothrix infection still poses a potential
      threat to the economy of the farmed animal industry, as well as being a potential
      human public health hazard.

PMID- 11972688
TI  - Growth studies of potentially probiotic lactic acid bacteria in cereal-based
      substrates.
AB  - AIMS: The overall growth kinetics of four potentially probiotic strains
      (Lactobacillus fermentum, Lact. reuteri, Lact. acidophilus and Lact. plantarum)
      cultured in malt, barley and wheat media were investigated. The objectives were
      to identify the main factors influencing the growth and metabolic activity of
      each strain in association with the cereal substrate. METHODS AND RESULTS: All
      fermentations were performed without pH control. A logistic-type equation, which
      included a growth inhibition term, was used to describe the experimental data. In
      the malt medium, all strains attained high maximum cell populations (8.10-10.11
      log10 cfu ml(-1), depending on the strain), probably due to the availability of
      maltose, sucrose, glucose, fructose (approx. 15 g l(-1) total fermentable sugars)
      and free amino nitrogen (approx. 80 mg l(-1)). The consumption of sugars during
      the exponential phase (10-12 h) resulted in the accumulation of lactic acid (1.06
      1.99 g l(-1)) and acetic acid (0.29-0.59 g l(-1)), which progressively decreased
      the pH of the medium. Each strain demonstrated a specific preference for one or
      more sugars. Since small amounts of sugars were consumed by the end of the
      exponential phase (17-43%), the decisive growth-limiting factor was probably the
      pH, which at that time ranged between 3.40 and 3.77 for all of the strains.
      Analysis of the metabolic products confirmed the heterofermentative or
      homofermentative nature of the strains used, except in the case of Lact.
      acidophilus which demonstrated a shift towards the heterofermentative pathway.
      All strains produced acetic acid during the exponential phase, which could be
      attributed to the presence of oxygen. Lactobacillus plantarum, Lact. reuteri and
      Lact. fermentum continued to consume the remaining sugars and accumulate
      metabolic products in the medium, probably due to energy requirements for cell
      viability, while Lact. acidophilus entered directly into the decline phase. In
      the barley and wheat media all strains, especially Lact. acidophilus and Lact.
      reuteri, attained lower maximum cell populations (7.20-9.43 log10 cfu ml(-1))
      than in the malt medium. This could be attributed to the low sugar content (3-4 g
      l(-1) total fermentable sugar for each medium) and the low free amino nitrogen
      concentration (15.3-26.6 mg l(-1)). In all fermentations, the microbial growth
      ceased at pH values (3.73-4.88, depending on the strain) lower than those
      observed for malt fermentations, which suggests that substrate deficiency in
      sugars and free amino nitrogen contributed to growth limitation. CONCLUSIONS: The
      malt medium supported the growth of all strains more than barley and wheat media
      due to its chemical composition, while Lact. plantarum and Lact. fermentum
      appeared to be less fastidious and more resistant to acidic conditions than Lact.
      acidophilus and Lact. reuteri. SIGNIFICANCE AND IMPACT OF THE STUDY: Cereals are
      suitable substrates for the growth of potentially probiotic lactic acid bacteria.

PMID- 11972689
TI  - Inactivation of Saccharomyces cerevisiae in solution by low-amperage electric
      treatment.
AB  - AIMS: The objectives of this study were to investigate the potential application
      of a low-amperage direct electric current as a non-thermal process for
      inactivation of Saccharomyces cerevisiae. METHODS AND RESULTS: Electric current
      was generated using a direct current power supply connected to a traditional
      electrochemical cell with two platinum electrodes immersed in conducting solution
      containing a population of S. cerevisiae. This treatment provoked inactivation of
      the yeast cells. The microbial destruction illustrated by D-values calculated
      from survival curves was shown to be proportional to the current amperage (i) (D
      varies from 1547 min to 140 min when i varies from 0.1 to 1 A, respectively). The
      efficacy of the treatment was shown to be better at pH < 7. Statistical analysis
      showed no significant effect (P > 0.05) of ionic strength on yeast lethality
      induced by electrolysis. CONCLUSIONS: The lethal effect of the electric treatment
      on S. cerevisiae in phosphate buffer was shown to be due to neither ohmic heating
      nor toxic hydrogen peroxide. A synergistic effect of temperature and electrolysis
      was observed when the temperature became lethal for the yeast. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The method described for yeast lethality induced by
      electrolysis has potential for soft sterilization, particularly when combined
      with the synergistic effect of moderate heat.

PMID- 11972690
TI  - The antibacterial activity of vancomycin towards Staphylococcus aureus under
      aerobic and anaerobic conditions.
AB  - AIMS: To investigate the antibacterial efficacy of vancomycin towards
      Staphylococcus aureus under aerobic and anaerobic conditions, and to assess the
      influence of oxygen on the duration of the post-antibiotic effect (PAE) after
      exposure to vancomycin. METHODS AND RESULTS: Culture-based techniques and flow
      cytometric measurements of 5-cyano-2,3-ditolyl tetrazolium chloride (an indicator
      of redox activity) and the membrane potential-sensitive fluorophore Sytox Green,
      were used to test four staphylococcal strains. The MICs for all strains, and the
      duration of PAE, were similar whether tested with or without oxygen. However, a
      fivefold logarithmic reduction in cell counts was observed in 10-15 h
      aerobically, depending on strain, compared with longer than 60 h in an anaerobic
      environment. Flow cytometric data correlated well with counts of colony-forming
      units under both aerobic and anaerobic conditions. CONCLUSIONS: The death rate of
      Staph. aureus exposed to vancomycin was greater in the presence of oxygen,
      although MIC values and PAE durations were similar whether tested aerobically or
      anaerobically. Also, flow cytometry provided a rapid and sensitive alternative to
      plate counts for the assessment of antibiotics in oxygen-free conditions.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study underlines the need for further
      anaerobic testing using different strain/antibiotic combinations, the results of
      which will have clinical significance due to the anaerobic nature of some sites
      of infection.

PMID- 11972691
TI  - Effect of package and storage conditions on viability and efficacy of the freeze
      dried biocontrol agent Pantoea agglomerans strain CPA-2.
AB  - AIMS: To reduce concentrations of protective and rehydrating media and to
      evaluate the effect of storage temperature, packaging and atmosphere conditions
      on the stability of freeze-dried Pantoea agglomerans cells. Efficacy against
      Penicillium digitatum of freeze-dried cells in orange fruits was also evaluated.
      METHODS AND RESULTS: Several concentrations of protective and rehydration media
      were tested to reduce processing costs. Freeze-dried cells were packed in glass
      vials or plastic bags under vacuum or nitrogen conditions at 4 and 25 degrees C.
      After 1 and 3 months, efficacy of freeze-dried P. agglomerans against P.
      digitatum was tested. CONCLUSIONS: The results indicate that it is possible to
      reduce the concentration of non-fat skimmed milk as a rehydration medium from 10%
      to 1%, maintaining viabilities of 100%. Moreover, freeze-dried cells could be
      stored in glass vials or in high barrier plastic bags at 4 degrees C for 3 months
      while maintaining high viabilities and efficacy against P. digitatum.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The major obstacle in the commercialization
      of biocontrol products is the development of a shelf-stable formulated product
      that retains biocontrol activity at a level similar to that of fresh cells. This
      study suggests that it is possible to maintain viability and efficacy of freeze
      dried P. agglomerans cells for at least 3 months.

PMID- 11972692
TI  - Bacillus megaterium spore germination is influenced by inoculum size.
AB  - AIMS: The effect of spore density on the germination (time-to-germination,
      percent germination) of Bacillus megaterium spores on tryptic soy agar was
      determined using direct microscopic observation. METHODS AND RESULTS: Inoculum
      size varied from approximately 10(3) to 10(8) cfu ml(-1) in a medium where pH=7
      and the sodium chloride concentration was 0.5% w/v. Inoculum size was measured by
      global inoculum size (the concentration of spores on a microscope slide) and
      local inoculum size (the number of spores observed in a given microscope field of
      observation). Both global and local inoculum sizes had a significant effect on
      time-to-germination (TTG), but only the global inoculum size influenced the
      percentage germination of the observed spores. CONCLUSIONS: These results show
      that higher concentrations of Bacillus megaterium spores encourage more rapid
      germination and more spores to germinate, indicating that low spore populations
      do not behave similarly to high spore populations. SIGNIFICANCE AND IMPACT OF THE
      STUDY: A likely explanation for the inoculum size-dependency of germination would
      be chemical signalling or quorum sensing between Bacillus spores.

PMID- 11972693
TI  - Achieving hygiene in the domestic kitchen: the effectiveness of commonly used
      cleaning procedures.
AB  - AIMS: To quantify the transmission of Salmonella and Campylobacter to hands,
      cloths, and hand- and food-contact surfaces during the preparation of raw poultry
      in domestic kitchens, and to examine the impact on numbers of these bacteria of
      detergent-based cleaning alone, or in conjunction with thorough rising. METHODS
      AND RESULTS: Groups of volunteers prepared chickens for cooking. Surfaces were
      sampled either before cleaning or after cleaning using water and detergent with
      or without thorough rinsing. Although cleaning followed by rinsing consistently
      achieved decontamination of surfaces contaminated with Campylobacter, significant
      numbers of surfaces were still contaminated with low numbers of Salmonella. Where
      cloths contaminated with Salmonella were stored overnight, a reduction in the
      efficacy of detergent-based cleaning regimes was observed. CONCLUSIONS: Rinsing
      is the critical step in ensuring that bacteria are removed from surfaces during
      cleaning, but this may still leave residual contamination. Growth of Salmonella
      occurs in some contaminated cloths during overnight storage; Salmonella on cloths
      stored overnight are also more difficult to remove by washing. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Rinsing, as part of the cleaning process, is a critical step
      in achieving hygiene in the kitchen. However, to achieve completely hygienic
      surfaces, the use of an antimicrobial agent may be necessary.

PMID- 11972694
TI  - Washing and chilling as critical control points in pork slaughter hazard analysis
      and critical control point (HACCP) systems.
AB  - AIMS: The aim of this research was to examine the effects of preslaughter
      washing, pre-evisceration washing, final carcass washing and chilling on final
      carcass quality and to evaluate these operations as possible critical control
      points (CCPs) within a pork slaughter hazard analysis and critical control point
      (HACCP) system. METHODS AND RESULTS: This study estimated bacterial numbers
      (total viable counts) and the incidence of Salmonella at three surface locations
      (ham, belly and neck) on 60 animals/carcasses processed through a small
      commercial pork abattoir (80 pigs d(-1)). Significant reductions (P < 0.05) in
      bacterial numbers were noted at some stages of the slaughter/dressing process,
      i.e. the process of hair removal (scalding-dehairing and singeing) resulted in an
      approx. 4.5 log10 cfu cm(-2) decrease in bacterial numbers. A significant
      increase (P < 0.05) in bacterial numbers was observed after pre-evisceration
      washing. Final washing increased the bacterial counts to between 3.6 and 3.8
      log10 cfu cm(-2) while chilling effected a small but statistically significant (P
      < 0.05) increase to between 4.5 and 4.7 log10 cfu cm(-2). The incidence of
      Salmonella on pigs at the farm was 27%, decreasing to 10% after preslaughter
      washing. However, stunning and bleeding effected a considerable increase in
      Salmonella contamination and the incidence after these operations was 50%, which
      was reduced to 0% during the scalding-dehairing process. CONCLUSIONS: Washing the
      live animals and subsequent carcasses with cold water is not an effective control
      measure but chilling may be used as a CCP. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Recent changes in European Union legislation legally mandate HACCP in pork
      slaughter plants. This research will provide a sound scientific basis on which to
      develop and implement effective HACCP in pork abattoirs.

PMID- 11972695
TI  - Comparison of adhesion of the food spoilage bacterium Shewanella putrefaciens to
      stainless steel and silver surfaces.
AB  - AIMS: To compare the number of attached Shewanella putrefaciens on stainless
      steel with different silver surfaces, thus evaluating whether silver surfaces
      could contribute to a higher hygienic status in the food industry. METHODS AND
      RESULTS: Bacterial adhesion to three types of silver surface (new silver,
      tarnished silver and sulphide-treated silver) was compared with adhesion to
      stainless steel (AISI 316) using the Malthus indirect conductance method to
      estimate the number of cfu cm(-2). The number of attached bacteria on new silver
      surfaces was lower than on steel for samples taken after 24 h. However, this was
      not statistically significant (P > 0.05). The numbers of attached bacteria were
      consistently lower when tarnished silver surfaces were compared with stainless
      steel and some, but not all, experiments showed statistical significance (P <
      0.05). Treating new silver with sulphide to reproduce a tarnished silver surface
      did not result in a similar lowering of adhering cells when compared with steel
      (P > 0.05). CONCLUSIONS: New or tarnished silver surfaces caused a slight
      reduction in numbers of attached bacteria; however, the difference was only
      sometimes statistically significant. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      lack of reproducibility in differences in numbers adhering to the different
      surfaces and lack of statistical significance between numbers of adhered viable
      bacteria do not indicate that the tested silver surfaces can be used to improve
      hygienic characteristics of surfaces in the food industry.

PMID- 11972696
TI  - Discrimination of Bacillus cereus and Bacillus thuringiensis with 16S rRNA and
      gyrB gene based PCR primers and sequencing of their annealing sites.
AB  - AIMS: To evaluate the possibility for discrimination of Bacillus cereus and B.
      thuringiensis using 16S rRNA and gyrB gene based PCR methods, and to obtain the
      sequences of the primer annealing sites so that the PCR results may be explained.
      METHODS AND RESULTS: Based on the sequence difference in the variable region (V1)
      of 16S rRNA and in the gyrB gene between B. cereus and B. thuringiensis, PCR
      primers specific to these Bacillus spp. were designed. When these primers were
      used to discriminate B. cereus and B. thuringiensis, six of 82 B. cereus strains
      were identified as B. thuringiensis while 67 of 73 B. thuringiensis strains were
      identified as B. cereus. Sequence analysis of the primer annealing sites showed
      that there is no clear-cut difference in the V1 region of 16S rRNA, and in the
      gyrB gene, between B. cereus and B. thuringiensis strains. CONCLUSIONS: Although
      16S rDNA based probes and gyrB gene based PCR primers have been suggested for the
      discrimination of B. cereus and B. thuringiensis strains, when a large number of
      Bacillus strains was tested, results showed that discrimination between B. cereus
      and B. thuringiensis is difficult. Therefore, to distinguish B. thuringiensis
      from B. cereus, a single feature, such as the presence of a parasporal crystal
      protein or cry gene, may sometimes be reliable. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Discrimination between B. cereus and B. thuringiensis is a challenging
      debate to which this paper makes a contribution.

PMID- 11972697
TI  - Enhancement of solar inactivation of Escherichia coli by titanium dioxide
      photocatalytic oxidation.
AB  - AIMS: To improve solar water disinfection using a photocatalysing semi-conductor
      and to study the mechanisms involved in this process. METHODS AND RESULTS: Cells
      of Escherichia coli were used as the microbiological indicator to study the
      possibility of improving the efficiency of solar water disinfection using
      titanium dioxide (TiO2) as a photooxidizing semi-conductor. TiO2 was used either
      as a suspended powder or in an immobilized form. Both applications improved the
      efficiency of solar disinfection. TiO2 in suspension was more effective than the
      immobilized form, producing enhancement factors of 1.62 and 1.34, respectively.
      The concentration of TiO2 greatly affected efficiency, with a maximum effect at 1
      mg ml(-1). Higher TiO2 concentrations reduced the efficiency. Dimethyl sulphoxide
      (DMSO) and cysteamine (Cys), hydroxyl radical (OH.) scavengers, were used to
      elucidate the mechanisms involved in the presence of TiO2. Both DMSO and Cys
      totally abolished the enhancing effect produced by the presence of TiO2.
      CONCLUSIONS: Sunlight has a potential water disinfecting capacity. The use of
      TiO2 greatly improved this efficiency. The effect of TiO2 was mainly
      concentration-dependent, giving maximum efficiency at 1 mg ml(-1). The presence
      of DMSO and Cys removed the TiO2-induced enhancement, indicating that OH. may be
      involved in the process of cell killing. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The efficiency of solar disinfection is limited and time-consuming and needs to
      be improved. The use of a semi-conductor is promising as it reduces the time of
      exposure and therefore increases the efficiency of solar disinfection. This would
      allow for the availability of good quality water, and hence would improve the
      quality of life.

PMID- 11972698
TI  - Improvement of Candida sake biocontrol activity against post-harvest decay by the
      addition of ammonium molybdate.
AB  - AIM: To improve the efficacy of Candida sake by adding ammonium molybdate to
      control post-harvest decay in Golden Delicious apples. METHODS AND RESULTS: In
      laboratory trials, C. sake 2 x 10(6) cfu ml(-)1 plus 5 mmol l(-1) ammonium
      molybdate greatly reduced Penicillium expansum, Botrytis cinerea or Rhizopus
      stolonifer in apples stored at 20 degrees C for 7 days, and reduced by more than
      90% blue and grey mould in apples stored at 1 degrees C for 60 days. The
      consistency of these results was maintained in semi-commercial trials at 1
      degrees C in air and in a low oxygen atmosphere for 120 days. The pre-harvest
      application of C. sake 2 x 10(7) cfu ml(-1) plus 1 mmol l(-1) ammonium molybdate
      did not improve post-harvest biocontrol of blue mould. The population of C. sake
      significantly decreased in the presence of ammonium molybdate in apple wounds.
      CONCLUSION: The addition of ammonium molybdate at 5 mmol l(-1) to C. sake
      enhanced the efficacy of the antagonist to control post-harvest diseases on
      apples. SIGNIFICANCE AND IMPACT OF THE STUDY: Ammonium molybdate significantly
      reduces the amount of C. sake biomass required to achieve post-harvest disease
      control, with a consequent reduction in costs. This may be useful in the
      industrial production of C. sake.

PMID- 11972699
TI  - Production of a monoclonal antibody against Aeromonas hydrophila and its
      application to bacterial identification.
AB  - AIMS: to develop a monoclonal antibody (MAb) for the rapid detection of Aeromonas
      hydrophila in human faeces. METHODS AND RESULTS: A monoclonal antibody with
      strong specificity against Aer. hydrophila was obtained by the fusion of myeloma
      cells and splenocytes of a mouse immunized with vegetative cells of Aer.
      hydrophila ATCC 7966, followed by a two-step selection against other species of
      the genera. ELISA analyses revealed that MAb 5F3 strongly reacts with all the
      Aer. hydrophila strains evaluated, showing a just basal reactivity against other
      species of the genera, especially Aer. sobria and Aer. caviae. CONCLUSIONS: MAb
      5F3 was characterized as an IgG that recognized a polypeptide of approximately
      110 kDa. SIGNIFICANCE AND IMPACT OF THE STUDY: This MAb could be used to detect
      Aer. hydrophila in human stool samples.

PMID- 11972700
TI  - Sensory, chemical and bacteriological changes during storage of iced squid
      (Todaropsis eblanae).
AB  - AIMS: To relate sensory shelf-life of iced whole and gutted squid to bacterial
      growth and chemical changes. METHODS AND RESULTS: Cooked mantles from whole and
      gutted individuals were rejected after 10 and 12 days of storage, respectively,
      due to ammoniacal off-odours. Rate of production of both ammonia and
      trimethylamine was highest in the whole lot. Agmatine, which was only present in
      trace amounts in freshly-caught squid, increased rapidly in both lots. The main
      microflora at the time of sensory rejection of iced whole squid included Gram
      negative, motile and non-fermentative rods, which were psychrophilic and had a
      requirement for NaCl. 16S rDNA sequence analyses identified the strains as
      belonging to the genus Pseudoalteromonas. Shewanella putrefaciens,
      Pseudoalteromonas sp. and Pseudomonas sp. dominated in spoiled gutted squid.
      Identification of strains from the stomach and digestive gland of recently
      captured squid showed that the main flora consisted of Photobacterium
      phosphoreum. CONCLUSIONS: Spoilage of iced squid is likely to result from a
      combination of autolytic and bacterial changes. Agmatine seems to be an excellent
      freshness indicator. Photobacterium phosphoreum may contribute to spoilage
      through activity in the digestive gland, followed by diffusion of volatile
      compounds and amines to the mantle. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to
      the psychrophilic nature of P. phosphoreum and Pseudoalteromonas sp., spread
      plating and low temperature incubation are recommended for bacteriological
      evaluation of iced squid.

PMID- 11972701
TI  - Characterization of yellow-pigmented and motile enterococci isolated from
      intestines of the garden snail Helix aspersa.
AB  - AIMS: Enterococci associated with garden snails (Helix aspersa) were studied in
      order to obtain reliable species identification and characterization. METHODS AND
      RESULTS: Twelve yellow-pigmented and motile enterococci, isolated from the
      intestines of garden snails, were phenotypically close to Enterococcus
      casseliflavus, but they showed certain unusual biochemical characteristics. tRNA
      intergenic length polymorphism analysis (tDNA-PCR) divided all strains studied
      into two groups, in full agreement with biochemical test results. 16S rDNA
      sequencing, DNA base composition analysis and DNA-DNA hybridization results
      showed unambiguously that the enterococci studied belonged to the species Ent.
      casseliflavus. The representative strains of described ecovars were deposited in
      the Czech Collection of Microorganisms (CCM) as Ent. casseliflavus CCM 4868,
      4869, 4870 and 4871. CONCLUSIONS: Enterococcus casseliflavus associated with
      garden snails can be subdivided into groups. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Enterococcus casseliflavus differs from other enterococcal species in that
      it is typically associated with plants, soil, water and invertebrate animals. The
      different groups that can be found in these widely occurring bacteria are
      possibly source-specific ecovars, as exemplified by the Ent. casseliflavus
      inhabiting the intestines of snails.

PMID- 11972702
TI  - Metabolism by bifidobacteria and lactic acid bacteria of polysaccharides from
      wheat and rye, and exopolysaccharides produced by Lactobacillus sanfranciscensis.
AB  - AIMS: The metabolism by bifidobacteria of exopolysaccharide (EPS) produced by
      Lactobacillus sanfranciscensis was investigated. To evaluate the significance of
      the EPS produced by Lact. sanfranciscensis during dough fermentation on the
      overall prebiotic properties of bread, metabolism by bifidobacteria of water
      soluble polysaccharides (WSP) from wheat and rye was investigated. METHODS AND
      RESULTS: Polyglucose and polyfructan contained in WSP from wheat and rye were
      metabolized by bifidobacteria. In contrast, WSP isolated from fermented doughs
      were not metabolized by bifidobacteria. The arabioxylan fraction of WSP was
      metabolized neither by bifidobacteria nor by lactobacilli. All the bifidobacteria
      tested were able to metabolize fructan from Lact. sanfranciscensis. The kinetics
      of EPS metabolism by various bifidobacteria were characterized by diauxic
      utilization of fructose and EPS. CONCLUSIONS: Bifidobacteria metabolize fructan
      from Lact. sanfranciscensis. Polyfructan and the starch fractions from wheat and
      rye, which possess a bifidogenic effect, were degraded by cereal enzymes during
      dough fermentation, while the EPS were retained. SIGNIFICANCE AND IMPACT OF THE
      STUDY: EPS produced by sourdough lactic acid bacteria will improve the
      nutritional properties of sourdough fermented products.

PMID- 11972703
TI  - Characterization of lactobacilli towards their use as probiotic adjuncts in
      poultry.
AB  - AIMS: A total of 112 strains of lactic acid bacteria of duck origin were studied
      for their use as a probiotic feed supplement. METHODS AND RESULTS: In vitro
      studies included aggregation, co-aggregation, cell surface hydrophobicity and
      adhesion activities on poultry crop cells and human Hep2-cells. Additionally,
      growth with bile acids (chicken bile, ox gall and taurocholic acid) and tolerance
      to acidic pH were tested. Among all the isolates, two strains (Lactobacillus
      animalis TMW 1.972 and Lactobacillus salivarius TMW 1.992) were selected for a
      survival test in poultry. Monitoring and differentiation of these strains was
      achieved by selective detection as rifampicin and erythromycin double-resistant
      mutants. After a single feed administration, both micro-organisms were shown to
      persist in the crop and caecum of ducks for a period of 18 and 22 days,
      respectively. For identification of Lact. animalis and Lact. salivarius, two
      specific PCRs targeted against 16S rDNA were developed. CONCLUSIONS: Within the
      autochtoneous microflora of ducks, two strains of lactobacilli exhibited strong
      potential as probiotic adjuncts. The results indicate that the natural gut
      microflora of poultry serves as an excellent source for optimal strains.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A general strategy for the selection of
      probiotic strains is presented. The suggested sequence of tests allows
      identification of the most promising candidates within complex ecosystems or
      large strain collections with minimal expenditure.

PMID- 11972704
TI  - The enrichment of a ruminal bacterium (Megasphaera elsdenii YJ-4) that produces
      the trans-10, cis-12 isomer of conjugated linoleic acid.
AB  - AIMS: To isolate predominant ruminal bacteria that produce trans-10, cis-12
      conjugated linoleic acid (CLA) from linoleic acid (LA). METHODS AND RESULTS:
      Mixed bacteria from ruminal contents of a cow fed grain were enriched with DL
      lactate and trypticase. They produced more trans-10, cis-12 CLA than those that
      were not enriched (7 vs 2 microg mg protein(-1), P < 0.05). Enrichments had an
      abundance of large cocci that produced trans-10, cis-12 CLA from LA. Strain YJ-4
      produced the most trans-10, cis-12 CLA (approx. 7 microg mg protein(-1)) and 16S
      rDNA sequencing indicated that YJ-4 was a strain of Megasphaera elsdenii.
      Megasphaera elsdenii T81 produced approx. 4 microg trans-10, cis-12 CLA mg
      protein(-1) while strains B159, AW106 and JL1 produced < 0.5 microg mg protein(
      1). The trans-10, cis-12 CLA production of YJ-4 was first order with respect to
      cell concentration (0-800 microg protein ml(-1)), but kinetics were not first
      order with respect to substrate concentration. CONCLUSIONS: Some M. elsdenii
      strains produce significant amounts of trans-10, cis-12 CLA. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Trans-10, cis-12 CLA appears to cause milk fat depression in
      cattle fed diets supplemented with grain and polyunsaturated fatty acids, but
      predominant ruminal bacteria that produced trans-10, cis-12 CLA from LA had not
      previously been isolated.

PMID- 11972705
TI  - Polymerase chain reaction identification of Bacillus sporothermodurans from dairy
      sources.
AB  - AIMS: A new polymerase chain reaction (PCR) method for the identification of
      Bacillus sporothermodurans strains from sterilized or ultrahigh temperature
      treated milk and milk products and from other non-milk sources and environments,
      including the dairy farm. METHODS AND RESULTS: Two strains from raw milk and feed
      concentrate could be allocated to B. sporothermodurans based on 16S rDNA
      sequencing and DNA-DNA hybridization results. Two specific PCR primers were
      derived from the 16S rRNA gene of B. sporothermodurans. CONCLUSIONS: The PCR
      identification method was validated using a collection of B. sporothermodurans
      strains from different sources and on a large collection of dairy and non-dairy
      Bacillus spp. and other relevant taxa. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      PCR method was used as a screening method for strains with very heat-resistant
      endospores, isolated at the dairy farm level after heat treatment for 30 min at
      100 degrees C. Seventeen strains isolated at the dairy farm were identified as B.
      sporothermodurans. They originated mainly from feed concentrate and also from
      soy, pulp and silage. The PCR identification method described here can,
      therefore, contribute to a better understanding of the route by which B.
      sporothermodurans contaminates raw and/or heat-treated milk.

PMID- 11972706
TI  - Molecular epidemiology of cystic fibrosis-linked Burkholderia cepacia complex
      isolates from three national referral centres in Ireland.
AB  - AIMS: Burkholderia cepacia is a Gram-negative bacterium associated with
      increasing morbidity and mortality and is readily transmitted among infected
      cystic fibrosis (CF) patients. The B. cepacia complex consists of five distinct
      subgroups, termed genomovars. A collection of 17 presumptive B. cepacia isolates,
      obtained from three national CF referral centres located in different
      geographical regions in Ireland, was studied. The aim of this study was to
      investigate these isolates using molecular subtyping protocols for evidence of
      genetic relationships and for the presence of antibiotic resistance-encoding
      class 1 integron structures. METHODS AND RESULTS: Genomovar classifications were
      assigned to each isolate based on HaeIII enzyme profiles of their recA locus.
      Genetic relationships among this collection were also assessed after restriction
      fragment length polymorphism (RFLP)-mediated analysis of the 16S rDNA locus and
      DNA amplification fingerprinting (DAF). The surface expression of the cable pilus
      gene (cblA) may facilitate an early step in the infection process. All isolates
      were tested by amplification strategies for this marker. Burkholderia cepacia is
      known to be resistant to several antimicrobial agents. Resistance typing showed
      that the majority were resistant to three or more common antimicrobial agents.
      Five of the 17 isolates were resistant to sulphonamide, a characteristic linked
      with the presence of class 1 integrons. Gene cassettes containing beta-lactamase
      (oxa) and aminoglycoside acetyltransferase (aac(6')-1a) encoding genes were
      identified by polymerase chain reaction amplification. CONCLUSIONS: Most of the
      isolates in this study were classified as genomovar III and were
      indistinguishable based on their corresponding 16S rDNA-RFLP profiles, whilst DAF
      further subtyped the collection. The cblA marker was identified in 47% of the
      isolates, many of which clustered in the genomovar III group. Class 1 integrons
      with recombined gene cassettes containing bla-OXA and aac(6')-1a genes were
      identified. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the
      application of molecular methods to investigate B. cepacia, a well-recognized
      human pathogen, cultured from Irish CF patients. Genomovar III was the most
      common genomic type identified. DNA fingerprinting further subtyped the latter
      isolates, facilitating a more detailed description of the molecular epidemiology.
      Drug resistance in these organisms can be explained, at least in part, by the
      presence of class 1 integrons. Development of targeted infection control
      strategies could be facilitated using these applied methods.

PMID- 11972707
TI  - The occurrence of malolactic fermentation in brandy base wine and its influence
      on brandy quality.
AB  - AIMS: In this study we determined the extent to which lactic acid bacteria (LAB)
      occurred in brandy base wines, their ability to catalyse the malolactic
      fermentation (MLF) and the effect of MLF on the quality of the base wine and the
      brandy distillate. METHODS AND RESULTS: Lactic acid bacteria were isolated and
      enumerated from grape juice, experimental and commercially produced brandy base
      wines. Spontaneous MLF occurred in approximately 50% of the commercial base
      wines. The occurrence of MLF had an influence on the quality of the base wines
      and the resulting distillates. In samples where MLF occurred there was a loss of
      fruitiness and in the intensity of aroma. Volatile compounds like iso-amyl
      acetate, ethyl acetate, ethyl caproate, 2-phenethyl acetate and hexyl acetate
      decreased in samples having undergone MLF, while ethyl lactate, acetic acid and
      diethyl succinate increased in the same samples. CONCLUSIONS: Spontaneous
      malolactic fermentation does occur in commercial brandy base wines and it has an
      influence on base wine and brandy quality. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study showed that MLF influences the quality of the base wine and the
      resulting distillate and with this in mind commercial base wine producers should
      be able to produce brandy of higher quality.

PMID- 11972708
TI  - Elson B. Helwig, MD (1907-1999).

PMID- 11972709
TI  - Interstitial mycosis fungoides, a variant of mycosis fungoides resembling
      granuloma annulare and inflammatory morphea.
AB  - BACKGROUND: Interstitial mycosis fungoides (IMF) is a rare variant of mycosis
      fungoides that resembles the interstitial form of granuloma annulare and
      inflammatory morphea. IMF has received little attention in the literature.
      METHODS: Clinical, histological, immunophenotypical, and genotypical findings of
      five cases of IMF were reviewed. The histological and immunophenotypical findings
      were compared with those of eight cases of interstitial granuloma annulare and
      six cases of inflammatory morphea. RESULTS: Five patients with IMF presented with
      non-indurated, erythematous macules; ill-defined erythematous plaques with slight
      scale; and nodules on the trunk and proximal limbs. Two of five patients had a
      prior diagnosis of mycosis fungoides. Skin biopsies revealed a striking dermal
      interstitial infiltrate of lymphocytes with rare histiocytes that resembled the
      interstitial form of granuloma annulare or inflammatory morphea. Epidermotropic
      lymphocytes were present at least focally in all cases. A band-like lymphocytic
      infiltrate was observed in two of five cases. In contrast, many plasma cells and
      histiocytes were observed in cases of inflammatory morphea and interstitial
      granuloma annulare, respectively. With Movat-pentachrome stains, increased dermal
      mucin deposition was observed in two of five IMF cases, in all cases of
      interstitial granuloma annulare, and in one of six cases of inflammatory morphea.
      There was focal loss of elastic fibers in all cases of inflammatory morphea.
      Immunohistochemical studies of IMF highlighted a dominant population of T cells
      (CD3+) in the dermis and epidermis. In contrast, moderate numbers of B cells
      (CD20+) were admixed with T cells and plasma cells in inflammatory morphea.
      Almost equal numbers of histiocytes (CD68+) and T cells comprised the infiltrate
      of interstitial granuloma annulare. In two of five IMF cases, a clonal T-cell
      population was detected by PCR T-cell gamma gene rearrangement analysis.
      CONCLUSION: Mycosis fungoides occasionally presents as an interstitial
      lymphocytic infiltrate that mimics granuloma annulare and inflammatory morphea.
      Hematoxylin & eosin (H&E) findings alone can sometimes distinguish the three
      disorders. Immunophenotyping and genotyping may be helpful in difficult cases.

PMID- 11972710
TI  - Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) at
      sites typical for Borrelia burgdorferi infection.
AB  - BACKGROUND: Cutaneous manifestations of B-cell chronic lymphocytic leukemia (B
      CLL) comprise a wide spectrum of clinicopathologic presentations. In some cases,
      onset of skin lesions is triggered by antigenic stimulation, and specific skin
      infiltrates at sites of previous herpes simplex or herpes zoster infection have
      been well documented. Specific skin manifestations of B-CLL can also be observed
      at sites typical for lymphadenosis benigna cutis (nipple, scrotum, earlobe), a
      Borrelia burgdorferi-associated cutaneous B-cell pseudolymphoma. METHODS: We
      studied specific skin manifestations of B-CLL arising at sites typical for B.
      burgdorferi-induced lymphadenosis benigna cutis, analyzing tissues for presence
      of B. burgdorferi DNA using the polymerase chain reaction (PCR) technique. Six
      patients with B-CLL (M : F = 4 : 2; mean age: 67.8) presented with specific skin
      lesions located on the nipple (four cases) and scrotum (two cases). RESULTS:
      Clinically there were solitary erythematous plaques or nodules. Histology
      revealed in all cases a dense, monomorphous infiltrate of small lymphocytes
      showing an aberrant CD20+/CD43+ phenotype. In all cases monoclonality was
      demonstrated by PCR analysis of the JH gene rearrangement. PCR analysis showed in
      four of the six cases the presence of DNA sequences specific for B.burgdorferi.
      CONCLUSIONS: Our study demonstrates that infection with B. burgdorferi can
      trigger the development of specific cutaneous infiltrates in patients with B-CLL.

PMID- 11972711
TI  - Host-vs.-altered-host eruptions in patients on liposomal doxorubicin.
AB  - BACKGROUND: Anthracycline antitumor antibiotics are the most commonly used
      chemotherapeutic agents. One of these is doxorubicin. Liposomal doxorubicin was
      developed as a drug delivery system in order to deliver the active drug
      intracellularly while decreasing the systemic toxicity, particularly
      hematological and cardiac toxicity. METHODS: The clinical and histologic findings
      of the cutaneous eruptions of associated with liposomal doxorubicin are reviewed.
      RESULTS: The eruptions occurred in three women with metastatic ovarian carcinoma
      who were treated with liposomal doxorubicin. These three patients developed
      erythematous macular/papular to plaque cutaneous lesions, and in one patient a
      vesicular component. The eruptions involved the trunk and extremities
      approximately 3-4 weeks after completions of therapy. None of the patients had
      any documented infections, and none of the patients had symptoms other than
      pruritus. The eruptions cleared over a period of weeks to months. Histologic
      features included an interface dermatitis with numerous apoptotic/dyskeratotic
      cells within the epidermis, with involvement the intra-epidermal sweat ducts and
      the infundibulum of hair follicles. CONCLUSION: We believe that these eruptions
      represented a chemotherapy induced host-vs.-altered host reaction.

PMID- 11972712
TI  - Absence of HHV-8 DNA in hobnail hemangiomas.
AB  - BACKGROUND: Hobnail hemangioma (HH) is a rare subtype of hemangioma that shares
      the morphological feature of hobnail endothelia with retiform
      hemangioendothelioma (RHE) and has to be considered in the differential diagnosis
      of Kaposi sarcoma. Since DNA of the human herpesvirus type 8 (HHV-8) has been
      detected in more than 90% of Karposi sarcomas and could recently be demonstrated
      in RHE, we sought to detect HHV-8 DNA in HH. METHODS AND RESULTS: DNA from 12 HH
      was extracted and subjected to polymerase chain reaction analysis for HHV-8 DNA
      using two independent protocols with a single set of primers and a nested PCR
      approach, respectively. PCR amplification was performed using the LightCycler as
      well as using a thermocycler. HHV-8 DNA could not be detected in HH, although
      each sample contained DNA adaequately preserved for PCR reactions, as determined
      by amplification of the beta actin gene. CONCLUSIONS: HHV-8 appears to play no
      rule in the pathogenesis of HH. Absence of HHV-8 DNA in HH might be important in
      the differential diagnosis to other vascular tumours, in particular Kaposi
      sarcoma.

PMID- 11972713
TI  - Heavy multinodular cutaneous lymphoid infiltrates: clinicopathologic features and
      B-cell clonality.
AB  - BACKGROUND: Criteria for distinguishing between cutaneous lymphoid hyperplasia
      (CLH) and low-grade B-cell lymphoma are not well defined. We examined the
      hypothesis that the presence of a clonal B-cell population in heavy multinodular
      lymphoid infiltrates correlates with clinical presentation and outcome. METHODS:
      We identified 29 patients with skin lesions characterized histologically by a
      heavy dermal lymphocytic infiltrate with a multinodular architecture and
      extension into deep dermis and subcutaneous fat. Clonality was assessed
      immunophenotypically by light-chain restriction and also by analysis for IgH-gene
      rearrangement using PCR on DNA extracted from paraffin blocks. RESULTS: Follow-up
      (mean 80 months; median 45 months) was obtained in all patients. Twenty-four
      patients (83%) presented with a solitary lesion: only four had solitary
      recurrences, and none developed multiple synchronous lesions or systemic B-cell
      lymphoma. However, 9/24 of these solitary lesions (38%) were clonal by light
      chain restriction or IgH PCR; 5/29 patients (17%) presented with multiple
      recurrent lesions and continued to develop lesions during the period of follow
      up; 3/5 patients (60%) with multiple lesions demonstrated a B-cell clone. No
      patient developed systemic B-cell lymphoma. CONCLUSIONS: Heavy, multinodular
      cutaneous lymphoid infiltrates have an excellent prognosis. Multiple lesions at
      presentation are the best predictor of recurrent multiple lesions confined to the
      skin. The presence of a clonal B-cell population does not correlate with clinical
      presentation or histology, nor does it predict development of further lesions or
      systemic lymphoma.

PMID- 11972714
TI  - Epidemiology and microbiology of cellulitis and bacterial soft tissue infection
      during HIV disease: a 10-year survey.
AB  - BACKGROUND: Cellulitis and soft tissue infection are underestimated complications
      of HIV disease. PATIENTS AND METHODS: Sixty-seven bacteriologically proven
      consecutive episodes were identified among 2221 HIV-infected patients
      hospitalized in a 10-year period, and assessed according to several
      epidemiological, microbiological and clinical variables. RESULTS: Staphylococcus
      aureus was the most frequently cultured pathogen (50% of 92 isolates), followed
      by Pseudomonas spp., Escherichia coli and Streptococcus pyogenes; a polymicrobial
      infection was present in 38.1% of episodes. Drug addiction (p < 0.003) and male
      gender (p < 0.04) were significantly associated with the occurrence of these
      complications, which were community-acquired in 83.6% of cases. While a
      remarkable variation in the severity of underlying immunodeficiency was shown,
      hematogenous dissemination occurred in 25.4% of episodes, and proved
      significantly related to a low CD4+ lymphocyte count, and neutropenia. A 21.7%
      methicillin-resistance rate was shown among S. aureus isolates. All episodes were
      favorably treated in 5-16 days, in over 60% of cases with associated beta-lactam
      aminglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in
      four patients only. CONCLUSION: Skin and soft tissue infections are continuing
      causes of morbidity in HIV-infected patients, even in the highly active
      antiretroviral therapy era.

PMID- 11972715
TI  - Nanobacteria and calcinosis cutis.
AB  - BACKGROUND: The nanobacteria are a recently characterized group of extremely
      small bacteria capable of precipitating calcium salts implicated in the
      pathogenesis of urinary calculi and calcific atherosclerosis. The pathogenesis of
      calcinosis cutis and its significance in conjunction with a variety of unrelated
      scarring and pre-existing cutaneous entities are incompletely understood.
      METHODS: A series of cases, including basal cell carcinoma with dystrophic
      calcification, subepidermal calcified nodule, pilomatricoma, and tumoral
      calcinosis, were ultrastructurally examined for the presence of Nanobacteria sp.
      RESULTS: All cases, including three basal cell carcinomas, two subepidermal
      calcified nodules, three cases of pilomatricoma, and two cases of tumoral
      calcinosis, were negative for Nanobacteria. CONCLUSIONS: The dystrophic
      calcification that occurs in conjunction with the above entities does not likely
      involve a bacterial-induced etiology. The cause of these entities remains
      unknown.

PMID- 11972716
TI  - Platelet involvement in cutaneous small vessel vasculitis.
AB  - BACKGROUND: Secretory products of platelets serve important functions in
      inflammation and thrombosis. Participation of platelets in the tissue reaction
      associated with cutaneous small vessel vasculitis has not yet been evaluated, so
      we systematically investigated the presence of platelet aggregates in inflamed
      microvessels. METHODS: Thirty-six biopsies containing vasculitis and 18 biopsies
      with perivascular or interface type dermatitis were reviewed and adjacent
      sections were immunohistochemically stained with anti-CD61 antibody recognizing
      GPIIbIIIa receptors on platelets and with anti-von Willebrand factor (anti-vWF)
      antibody. RESULTS: Platelet aggregates were observed in 27 (75%) of the
      vasculitis biopsies and three (16.7%) of the perivascular dermatitis biopsies, of
      which two (11%) had traumatic vessel damage. In all vasculitis cases, platelet
      clumps were associated with diffuse immunostaining of the perivascular stroma
      with the initiator of platelet aggregation anti-vWF. In the non-vasculitis type
      of dermatitis anti-vWF staining remained strictly limited to the cytoplasm of
      endothelial cells in 10 cases, and in eight cases there was also slight diffuse
      perivascular staining, albeit less extensively than in vasculitis cases.
      CONCLUSION: Formation of platelet aggregates appears to play a thus far
      unrecognized role in cutaneous small vasculitis. Secretory products of platelets
      will likely contribute to the inflammatory response and tissue damage in
      vasculitis. Moreover, platelet immunohistochemistry may be helpful in the
      diagnosis of microvascular damage in paraffin sections.

PMID- 11972717
TI  - Primary cutaneous CD30 (Ki-1)-positive non-anaplastic B-cell lymphoma.
AB  - BACKGROUND: The CD30 (Ki-1)-positive lymphoproliferative disorders show a non
      epidermotropic infiltrate of large-sized pleomorphic T cells, being extremely
      rare those that develop from B cells. CLINICAL CASE: A 51-year-old white man
      presented with a 8x10 cm lobulated scalp tumor that had developed during the
      previous 8 months. Histopathology demonstrated a proliferation of medium and
      large-sized non-anaplasic lymphocytes. The tumor cells (CD45+) expressed B
      phenotype (CD20+, CD3) and were CD30 (Ki-1) positive. The extension study
      revealed no extracutaneous involvement and the lesion resolved following
      chemotherapy. Two years later, after six cycles of chemotherapy that followed the
      CHOP protocol the patient remained asymptomatic. CONCLUSIONS: We report a patient
      with a diffuse lymphoma of medium and large-sized B phenotype cells on the scalp
      that showed the unusual characteristic of being both non-anaplastic and CD30 (Ki
      1) positive.

PMID- 11972718
TI  - Fibroepithelioma-like changes occurring in perianal Paget's disease with rectal
      mucinous carcinoma: case report and review of 49 cases of extramammary Paget's
      disease.
AB  - BACKGROUND: Anogenital Paget's disease (PD) may be accompanied by varying degrees
      of epidermal hyperplasia. The histological changes can be reminiscent of
      fibroepithelioma of Pinkus. METHODS: We present a case of perianal PD associated
      with fibroepitheliomatous epidermal hyperplasia in a 76-year-old-man with an
      underlying rectal mucinous carcinoma. We also carried out a retrospective
      analysis of 51 biopsies from 49 cases of extramammary PD to see whether
      particular epidermal changes occur in association with PD in different anatomic
      locations. RESULTS: A tumor, 3 cm in diameter, was noted in the patient's
      perianal skin. Histologically, it was composed of anastomosing thin epithelial
      strands with follicular differentiation. Paget's cells were distributed in the
      epithelial strands of this tumor as well as in the surrounding epidermis and anal
      epithelia. In our series of extramammary PD, epidermis was hyperplastic in two of
      two perianal cases, 26 of 43 genital skin samples, and one of six axillary PD
      biopsies. The stroma beneath the hyperplastic epidermis tended to be rich in thin
      collagen fibers and fibroblasts. CONCLUSIONS: Anogenital PD was more frequently
      associated with epidermal hyperplasia than axillary PD. Fibroepitheliomatous
      hyperplasia may be induced by the altered stroma associated with PD.

PMID- 11972719
TI  - EMLA cream-induced irritant contact dermatitis.
AB  - BACKGROUND: The Eutectic Mixture of Local Anesthetics (EMLA cream) is a topical
      anesthetic used for providing pain relief in patients undergoing superficial
      surgical procedures. Cutaneous side-effects have been reported rarely. CASE
      REPORT: We present a case of irritant contact dermatitis induced by EMLA cream in
      a 6-year-old boy with Wiskott-Aldrich syndrome. Our patient showed clinically a
      well circumscribed patch corresponding to the site of application of the topical
      anesthetic. Histopathology showed confluent necrosis of keratinocytes in the
      upper epidermis, a mixed inflammatory infiltrate with priminent neutrophils in
      the upper dermis, and focal signs of interface changes including basal cell
      vacuolization and subepidermal cleft formation. CONCLUSIONS: Graft-vs.-host
      disease (GVHD), necrolytic migratory erythema, dermatitis enteropathica and
      pellagra should be considered in the histopathologic differential diagnosis of
      acute contact dermatitis caused by EMLA.

PMID- 11972721
TI  - Survey of primary care physicians and home care clinicians.
AB  - CONTEXT: Providing home care in the United States is expensive, and significant
      geographic variation exists in the utilization of these services. However, few
      data exist on how well physicians and home care providers communicate and
      coordinate care for patients. OBJECTIVE: To assess communication and
      collaboration between primary care physicians (PCPs) and home care clinicians
      (HCCs) within 1 primary care network. DESIGN: Mail survey. SETTING: Boston.
      PARTICIPANTS: Sixty-seven PCPs from 1 academic medical center-affiliated primary
      care network and 820 HCCs from 8 regional home care agencies. MEASUREMENTS:
      Provider responses RESULTS: Ninety percent of PCPs and 63% of HCCs responded. The
      majority (54%) of PCPs reported that they only "rarely" or "occasionally" read
      carefully the home care order forms sent to them for signature. Further, when
      asked to rate their prospective involvement in the decision making about home
      care, only 24% of PCPs and 25% of HCCs rated this as "excellent" or "very good."
      Although more HCCs (79%) than PCPs (47%) reported overall satisfaction with
      communication and collaboration, 28% of HCCs felt they provided more services to
      patients than clinically necessary. CONCLUSIONS: PCPs from 1 provider network and
      the HCCs with whom they coordinate home care were both dissatisfied with many
      aspects of communication and collaboration regarding home care services.
      Moreover, neither group felt in control of home care decision making. These
      findings are of concern because poor coordination of home care may adversely
      affect quality and contribute to inappropriate utilization of these services.

PMID- 11972720
TI  - The relative importance of physician communication, participatory decision
      making, and patient understanding in diabetes self-management.
AB  - OBJECTIVE: Patients' self-management practices have substantial consequences on
      morbidity and mortality in diabetes. While the quality of patient-physician
      relations has been associated with improved health outcomes and functional
      status, little is known about the impact of different patient-physician
      interaction styles on patients' diabetes self-management. This study assessed the
      influence of patients' evaluation of their physicians' participatory decision
      making style, rating of physician communication, and reported understanding of
      diabetes self-care on their self-reported diabetes management. DESIGN: We
      surveyed 2,000 patients receiving diabetes care across 25 Veterans' Affairs
      facilities. We measured patients' evaluation of provider participatory decision
      making with a 4-item scale (Provider Participatory Decision-making Style
      [PDMstyle]; alpha = 0.96), rating of providers' communication with a 5-item scale
      (Provider Communication [PCOM]; alpha = 0.93), understanding of diabetes self
      care with an 8-item scale (alpha = 0.90), and patients' completion of diabetes
      self-care activities (self-management) in 5 domains (alpha = 0.68). Using
      multivariable linear regression, we examined self-management with the independent
      associations of PDMstyle, PCOM, and Understanding. RESULTS: Sixty-six percent of
      the sample completed the surveys (N = 1,314). Higher ratings in PDMstyle and PCOM
      were each associated with higher self-management assessments (P < .01 in all
      models). When modeled together, PCOM remained a significant independent predictor
      of self-management (standardized beta: 0.18; P < .001), but PDMstyle became
      nonsignificant. Adding Understanding to the model diminished the unique effect of
      PCOM in predicting self-management (standardized beta: 0.10; P =.004).
      Understanding was strongly and independently associated with self-management
      (standardized beta: 0.25; P < .001). CONCLUSION: For these patients, ratings of
      providers' communication effectiveness were more important than a participatory
      decision-making style in predicting diabetes self-management. Reported
      understanding of self-care behaviors was highly predictive of and attenuated the
      effect of both PDMstyle and PCOM on self-management, raising the possibility that
      both provider styles enhance self-management through increased patient
      understanding or self-confidence.

PMID- 11972722
TI  - Managed care, access to mental health specialists, and outcomes among primary
      care patients with depressive symptoms.
AB  - OBJECTIVE: To determine whether managed care is associated with reduced access to
      mental health specialists and worse outcomes among primary care patients with
      depressive symptoms. DESIGN: Prospective cohort study. SETTING: Offices of 261
      primary physicians in private practice in Seattle. PATIENTS: Patients (N =
      17,187) were screened in waiting rooms, enrolling 1,336 adults with depressive
      symptoms. Patients (n = 942) completed follow-up surveys at 1, 3, and 6 months.
      MEASUREMENTS AND RESULTS: For each patient, the intensity of managed care was
      measured by the managedness of the patient's health plan, plan benefit indexes,
      presence or absence of a mental health carve-out, intensity of managed care in
      the patient's primary care office, physician financial incentives, and whether
      the physician read or used depression guidelines. Access measures were referral
      and actually seeing a mental health specialist. Outcomes were the Symptom
      Checklist for Depression, restricted activity days, and patient rating of care
      from primary physician. Approximately 23% of patients were referred to mental
      health specialists, and 38% saw a mental health specialist with or without
      referral. Managed care generally was not associated with a reduced likelihood of
      referral or seeing a mental health specialist. Patients in more-managed plans
      were less likely to be referred to a psychiatrist. Among low-income patients, a
      physician financial withhold for referral was associated with fewer mental health
      referrals. A physician productivity bonus was associated with greater access to
      mental health specialists. Depressive symptom and restricted activity day
      outcomes in more-managed health plans and offices were similar to or better than
      less-managed settings. Patients in more-managed offices had lower ratings of care
      from their primary physicians. CONCLUSIONS: The intensity of managed care was
      generally not associated with access to mental health specialists. The small
      number of managed care strategies associated with reduced access were offset by
      other strategies associated with increased access. Consequently, no adverse
      health outcomes were detected, but lower patient ratings of care provided by
      their primary physicians were found.

PMID- 11972724
TI  - Developing an Internet-based communication system for residency training
      programs.
AB  - Administrative communication is increasingly challenging for residency programs
      as the number of training sites expands. The Internet provides a cost-effective
      opportunity to address these needs. Using the World Wide Web, we developed a
      single, reliable, accurate, and accessible source of administrative information
      for residents, faculty, and staff in a multisite internal medicine residency at
      reduced costs. Evaluation of the effectiveness of the website was determined by
      tracking website use, materials and personnel costs, and resident, staff, and
      faculty satisfaction. Office supply and personnel costs were reduced by 89% and
      personnel effort by 85%. All users were highly satisfied with the web
      communication tool and all reported increased knowledge of program information
      and a greater sense of "connectedness." We conclude that an internet-based
      communication system that provides a single, reliable, accurate, and accessible
      source of information for residents, faculty, and staff can be developed with
      minimum resources and reduced costs.

PMID- 11972723
TI  - Managed care, primary care, and the patient-practitioner relationship.
AB  - OBJECTIVES: This study examines how specific attributes of managed health plans
      influence patients' relationships with their primary care practitioners (PCPs)
      and determines whether these effects are mediated by access to, continuity with,
      or perceived choice of PCPs. DESIGN, SETTING, PATIENTS: The data source was the
      nationally representative 1996/97 Community Tracking Study Household Survey
      (cumulative response rate 65%). The study population (N = 19,415) was composed of
      18- to 64-year-old adults whose most recent visit in the past 12 months was made
      to their primary care delivery site. MAIN OUTCOME MEASURE: Patients' ratings of
      their interpersonal relationships with their PCPs as measured by a 7-item scale.
      RESULTS: Gatekeeping arrangements that require patients to select a primary care
      physician or obtain authorization for specialty referrals were associated with
      lower ratings of the patient-PCP relationship. Health plan use of a provider
      network had no effect on the patient-PCP scale score. Although there were no
      significant differences across any insurance payer categories, uninsured adults
      rated their relationships with PCPs as significantly poorer than did their
      insured counterparts. Shorter office waits, having a specific clinician at the
      primary care site, better perceived choice of PCPs, and a longer duration of
      relationship with the primary care practitioner were associated with higher
      ratings of the patient-PCP relationship. Perceived choice of primary care
      practitioners, but not access to or continuity with PCPs, attenuated some of the
      negative effects of gatekeeping arrangements on patients' relationships with
      their primary care practitioners. CONCLUSIONS: Managed health plans that loosen
      restrictions on provider choice, relax gatekeeping arrangements, or promote
      access to and continuity with PCPs, are likely to experience higher patient
      satisfaction with their primary care practitioner relationships. Lack of health
      insurance impedes the development of patients' relationships with their primary
      care practitioners.

PMID- 11972725
TI  - Medicare financing of graduate medical education.
AB  - The past decade has seen ongoing debate regarding federal support of graduate
      medical education, with numerous proposals for reform. Several critical problems
      with the current mechanism are evident on reviewing graduate medical education
      (GME) funding issues from the perspectives of key stakeholders. These problems
      include the following: substantial interinstitutional and interspecialty
      variations in per-resident payment amounts; teaching costs that have not been
      recalibrated since 1983; no consistent control by physician educators over direct
      medical education (DME) funds; and institutional DME payments unrelated to actual
      expenditures for resident education or to program outcomes. None of the current
      GME reform proposals adequately address all of these issues. Accordingly, we
      recommend several fundamental changes in Medicare GME support. We propose a re
      analysis of the true direct costs of resident training (with appropriate
      adjustment for local market factors) to rectify the myriad problems with per
      resident payments. We propose that Medicare DME funds go to the physician
      organization providing resident instruction, keeping DME payments separate from
      the operating revenues of teaching hospitals. To ensure financial accountability,
      we propose that institutions must maintain budgets and report expenditures for
      each GME program. To establish educational accountability, Residency Review
      Committees should establish objective, annually measurable standards for GME
      program performance; programs that consistently fail to meet these minimum
      standards should lose discretion over GME funds. These reforms will solve several
      long-standing, vexing problems in Medicare GME funding, but will also uncover the
      extent of undersupport of GME by most other health care payers. Ultimately,
      successful reform of GME financing will require "all-payer" support.

PMID- 11972726
TI  - Rational treatment choices for non-major depressions in primary care: an evidence
      based review.
AB  - OBJECTIVE: This review synthesizes available evidence for managing clinically
      significant dysphoric symptoms encountered in primary care, when formal criteria
      for major depression or dysthymia are not met. Discussion is focused on
      premenstrual dysphoric disorder (PMDD) and minor depression because of their
      significant prevalence in the primary care setting and the lack of clear practice
      guidelines for addressing each illness. DESIGN: English language literature from
      prior systematic reviews was supplemented by searching medline, embase, the
      Cochrane Controlled Trials Registry, the Agency for Healthcare Research and
      Quality National Guideline Clearinghouse, and bibliographies of selected papers.
      Studies addressing the natural history or treatment of minor depression or PMDD
      were selected for review. Data were abstracted by 1 of 2 independent reviewers
      and studies were synthesized qualitatively. RESULTS: Five individual studies that
      compared antidepressant or psychological treatments to placebo in patients with
      minor depression suggest short-term improvements in depressive symptoms with
      paroxetine, problem-solving therapy, and cognitive behavioral therapy, but not
      with amitryptiline. Modest benefits on mental health function were reported with
      paroxetine and with problem-solving therapy, but only in patients with severe
      functional impairment at baseline. Twenty-four controlled trials were identified
      that compared antidepressant or psychological treatments to placebo in patients
      with premenstrual dysphoric disorder. Pooled results from a recent systematic
      review of 15 randomized controlled trials and one additional trial abstract
      provide strong evidence for a significantly greater improvement in physical and
      psychological symptoms with serotonin-selective reuptake inhibitor medications
      when compared with placebo. Individual trials also suggest significantly greater
      improvements in symptom scores with venlafaxine, but not with tricyclic
      antidepressants. CONCLUSIONS: The limited evidence base for minor depression
      provides only mixed support for a small to moderate benefit for few
      antidepressant medications and psychological treatments tested. For the treatment
      of severe psychological or physical symptoms causing functional impairment in
      patients with PMDD, sertraline and fluoxetine are clearly beneficial in carefully
      selected patients.

PMID- 11972727
TI  - Evidence-based practice for mere mortals: the role of informatics and health
      services research.
AB  - The poor translation of evidence into practice is a well-known problem. Hopes are
      high that information technology can help make evidence-based practice feasible
      for mere mortal physicians. In this paper, we draw upon the methods and
      perspectives of clinical practice, medical informatics, and health services
      research to analyze the gap between evidence and action, and to argue that
      computing systems for bridging this gap should incorporate both informatics and
      health services research expertise. We discuss 2 illustrative systems--trial
      banks and a web-based system to develop and disseminate evidence-based guidelines
      (alchemist)--and conclude with a research and training agenda.

PMID- 11972737
TI  - Abstracts of the Society of General Internal Medicine 25th Annual Meeting.
      Atlanta, Georgia, USA. May 2-4, 2002.

PMID- 11972729
TI  - GME financing reform: the saga continues.

PMID- 11972738
TI  - Editorial: nutrition messages under the microscope.

PMID- 11972739
TI  - Dietary interventions in Finland, Norway and Sweden: nutrition policies and
      strategies.
AB  - AIMS: To describe the organization and implementation of nutrition policies, and
      examine intervention strategies for dietary change in three Scandinavian
      countries. METHODS: Descriptions of nutrition policies and dietary intervention
      strategies are based on published nutrition policy research and reports. RESULTS:
      All countries studied have adopted formal nutrition policies. Norway issued its
      first white paper in 1976, the Finnish National Nutrition Council published an
      action plan in 1989, and the Swedish Government issued an official action plan in
      1995. Norway has a centralized National Nutrition Council with a permanent
      administration whereas the responsibilities and administration are more spread
      out between several authorities and groups in Finland and Sweden. Amongst the
      dietary intervention strategies employed, a Norwegian nutrition campaign, symbol
      labelling of foods in Sweden, the community-based North Karelia Project in
      Finland, and mass catering in Finland and Sweden have been selected as
      potentially transferable. CONCLUSIONS: Policy documents serve as guidelines for
      activities and assist in achieving dietary targets. A responsible administrative
      body with advice from a standing expert committee is valuable for implementation.
      Guidelines, recommendations or voluntary labelling standards can be incentives to
      product development and changes to food production. Regional demonstration
      projects may also encourage action and collaboration.

PMID- 11972740
TI  - Relationship between omega3 long-chain polyunsaturated fatty acid status during
      early infancy and neurodevelopmental status at 1 year of age.
AB  - OBJECTIVE: To determine the influence of alpha-linolenic acid (ALA; 18 : 3omega3)
      intake and, hence, the influence of plasma and/or erythrocyte phospholipid
      content of docosahexaenoic acid (DHA; 22 : 6omega3) during early infancy on
      neurodevelopmental outcome of term infants. METHODS: The Bayley Scales of Infant
      Development (second edition), the Clinical Adaptive Test/Clinical Linguistic and
      Auditory Milestone Scale (CAT/CLAMS) and the Gross Motor Scale of the Revised
      Gesell Developmental Inventory were administered at a mean age of 12.26 +/- 0.94
      months to 44 normal term infants enrolled in a study evaluating the effects of
      infant formulas differing only in ALA content (0.4, 1.0, 1.7 and 3.2% of total
      fatty acids). RESULTS: As reported previously [Jensen et al., Lipids 13 (1996)
      107; J. Pediatr. 131 (1997) 200], the group fed the formula with the lowest ALA
      content had the lowest mean plasma and erythrocyte phospholipid DHA contents at 4
      months of age. This group also had the lowest mean score on every
      neurodevelopmental measure. The difference in mean gross motor developmental
      quotient of this group versus the group fed the formula with 1.0% ALA but not of
      the other groups was statistically significant (P < 0.05). Across the groups,
      motor indices correlated positively with each other and with the plasma
      phospholipid DHA content at 4 months of age (P=0.02-0.03). The CLAMS
      developmental quotient correlated with the erythrocyte phospholipid content of 20
      : 5omega3 (P < 0.01) but not with DHA. CONCLUSIONS: These statistically
      significant correlations suggest that the omega3 fatty acid status during early
      infancy may be important with respect to neurodevelopmental status at 1 year of
      age and highlight the need for further studies of this possibility.

PMID- 11972741
TI  - Five year results of a prospective very low calorie diet or conventional weight
      loss programme in type 2 diabetes.
AB  - AIMS: To complete 5-year follow-up of an intensive weight loss programme in
      established type 2 diabetic subjects. METHODS: Forty-five obese type 2 diabetic
      subjects, Body mass index (BMI) > 30, expressed interest in an intensive weight
      loss programme. Group 1 comprised 15 who selected very low calorie diet (VLCD),
      Group 2, 15 selected intensive conventional diet and exercise (ICD), 15 failed to
      follow either programme. Group sessions of eight to 15 subjects continued weekly
      for 6 months, then monthly for 12 months with prospective recording at 3, 6 and
      12 months and then annually of quality of life, BMI, waist/hip ratio, blood
      pressure, fasting blood glucose, serum fructosamine and serum lipids. RESULTS:
      Weight loss was slower in the intensive conventional diet group than in the VLCD
      group, but better maintained at 5 years: group 1, 4.8 +/- 6 kg; group 2, 8.9 +/-
      4 kg. In the intensive conventional diet group, 5 year high-density lipoprotein
      cholesterol was increased 1.78 +/- 0.26 mmol L-1 vs. 1.10 +/- 0.32 mmol L-1 at
      baseline, and diastolic blood pressure reduced 74.5 +/- 13.3 vs. 85.5 +/- 13.3 at
      baseline, both P < 0.05. CONCLUSIONS: Out-patient VLCD treatment proved safe and
      effective in overweight diabetic subjects but those who chose conventional diet
      and exercise had a slower but more sustained weight loss. Diabetic patients
      willing to attempt VLCD may safely lose sufficient weight to allow major surgery,
      but weight regain is inevitable. Patients willing to undertake a long-term group
      programme of conventional diet can sustain significant weight loss for 5 years,
      but still require antidiabetic medication.

PMID- 11972742
TI  - An investigation into school children's knowledge and awareness of food and
      nutrition.
AB  - With the diet and exercise behaviours of UK school children showing little
      improvement over recent years, the need for dietary change is clearly indicated.
      This study aimed to assess the nutritional knowledge and understanding of primary
      school children in order to identify the most effective format for future
      nutrition messages. A qualitative methodology was employed and 114 children, aged
      7-11 years, took part in 23 focus groups separated by age, gender and socio
      economic status (SES). Issues discussed included parental food rules, children's
      perceptions of 'good' and 'bad' foods, diet-disease links and food groupings.
      Across the groups restrictive food rules were most frequently reported whilst
      between groups gender and SES differences were apparent in relation to parental
      control over food and children's nutritional knowledge. The limitations of the
      children's cognitive development could be seen in their conceptualization of food
      groups, where concrete grouping schemes were frequently used, and in the lack of
      understanding inherent in their food-health or food-nutrient associations. Taste
      and preference were confirmed as consistent influences in children's food
      classification. Primary school children may be receptive to food based dietary
      guidelines based on familiar, concrete food classifications. These should be
      cognitively appropriate and possibly need to be gender specific.

PMID- 11972743
TI  - An audit of referrals of children with autistic spectrum disorder to the dietetic
      service.
AB  - Autistic spectrum disorder (ASD) is a developing area for dietetic referrals.
      There is little published data on current dietetic practice. Some children with
      ASD are referred for gluten/casein free diet. The theory is that abnormal
      metabolites in the urine may be a result of incomplete breakdown of gluten and
      casein in the gut. There are some published open studies that support the
      efficiency of such a diet [Knivsberg et al. (1995) Scand. J. Educ. Res.39: 223;
      Lucarelli et al. (1995) Panminerva Med.37: 137; Whiteley et al. (1999) Int. J.
      Res. Practice 3: 45] and also that there are many anecdotal reports that the diet
      helps some children. AIMS AND OBJECTIVES: This study aimed to audit the types of
      referral made to the dietetic service to identify key dietetic issues and to
      describe factors which may influence outcome/disease management. METHODS:
      Dietetic records were used to audit the referrals to the dietetic service over a
      3-month period. Seven-day diet histories were assessed using computer food
      composition tables and topics of interest recorded against a draft protocol
      agreed within the profession. RESULTS: Requests for gluten-free and casein-free
      dietetic advice, and/or the management of food selectivity and dysfunctional
      feeding behaviour constituted the majority of referrals. In many cases, child's
      environment was rarely simple. CONCLUSIONS: Despite the limitations of this small
      study, the findings suggest that the management of these referrals is highly
      complex. A dietitian's input should ensure that the nutritional adequacy of the
      diet is maintained or restored.

PMID- 11972744
TI  - The principles of dietary management of gestational diabetes: reflection on
      current evidence.
AB  - BACKGROUND: Gestational diabetes (GDM) is the commonest metabolic disorder of
      pregnancy. Most women with GDM are treated with nutritional management alone.
      There are conflicting guidelines surrounding its dietary management and this has
      resulted in a lack of conformity to the dietary advice currently prescribed.
      There is also conflicting opinions to the effectiveness of dietary management of
      GDM on pregnancy outcomes. The aim of this review was to examine the scientific
      evidence for the optimal nutritional management of GDM. METHODS: A Medline search
      of all English papers published between 1995 and 2001 that cross-referenced GDM
      with diet was under taken. Because of the poor quality of many of these papers,
      literature prior to 1995 known to the authors and considered relevant to the
      review were also included. RESULTS: The evidence base in this area is of poor
      quality. One systematic review based on randomized control trials failed to show
      any benefit from dietary intervention in GDM. However, that review did not
      include informative clinical and observational studies that are not classified as
      randomized controlled trials. Overall current evidence points to the
      effectiveness of dietary advice as a means of improving maternal hyperglycaemia
      and reducing the risk of accelerated foetal growth. The evidence surrounding
      energy restriction, carbohydrate and fat manipulation in GDM remains
      controversial. CONCLUSIONS: Current but limited evidence supports dietary
      alterations to reduce rates of accelerated foetal growth. There is a clear need
      for good quality randomized control trials in this area.

PMID- 11972746
TI  - Guidelines for diet in secondary prevention of cardiovascular disease.

PMID- 11972750
TI  - Transient vesicle leakage initiated by a synthetic apoptotic peptide derived from
      the death domain of neurotrophin receptor, p75NTR.
AB  - Peptides that induce apoptosis have potential as anticancer therapeutics. The
      design of safe, effective cancer therapeutic peptides requires characterization
      of the physical and chemical properties that influence activation of cell death
      in neoplastic cells. NTR365 is a synthetic pro-apoptotic peptide with an amino
      acid sequence derived from the death domain of p75(NTR). These studies were
      initiated to identify a potential mechanism for the apoptotic activity of NTR365
      identified by Rabizadeh et al. We examined the interactions of this synthetic pro
      apoptotic peptide with phospholipid vesicles. Fluorescence experiments
      demonstrate that the peptide induces leakage from large unilamellar vesicles.
      Leakage activity is transient and dependent on the presence of anionic lipid in
      the vesicles. Circular dichroism studies show that the NTR365 adopts a different
      conformation and may have altered vesicle affinity under conditions conducive to
      leakage. The active conformation of NTR365 differs from that of the NMR derived
      conformation. A related peptide with a single substitution is not apoptotically
      active, does not form a helical structure in the presence of vesicles and does
      not induce appreciable vesicle leakage under the same conditions as NTR365. These
      studies suggest that the demonstrated apoptotic activity of a closely related
      NTR364 peptide is linked to disruption of a membrane barrier and to the ability
      of the peptide to form a helical structure.

PMID- 11972749
TI  - Synthesis and analysis of potent, more lipophilic derivatives of the bradykinin
      B2 receptor antagonist peptide Hoe 140.
AB  - Bradykinin (BK) is an endogenous peptide that has been implicated in several
      pathological conditions, hence antagonists of its activity have therapeutic
      potential. The decapeptide Hoe 140 is currently one of the best BK antagonists,
      but interest remains in finding even more potent compounds. A library of Hoe 140
      derivatives was synthesized that incorporated non-natural analogs of the
      cationic, naturally occurring amino acids arginine (Arg) and lysine (Lys). The
      modified amino acids were designed to form enhanced ionic interactions due to an
      increase in local hydrophobicity, which promotes desolvation of the cation in
      water. The potencies of the resulting peptides were determined by competitive
      binding assays in human A431 cells expressing the BK B2 receptor. Two of the
      peptides synthesized were equipotent to Hoe 140 (IC(50s) 2.99 and 3.36 nM) and
      the most potent was demonstrated as a functional antagonist in vitro by blocking
      BK-mediated phosphorylation of mitogen-activated protein (MAP) kinases. The new
      derivatives are more hydrophobic than Hoe 140 and thus may exhibit changes in
      pharmacokinetic properties when evaluated in vivo.

PMID- 11972751
TI  - Mutational analysis of a blood coagulation factor VIII-binding peptide.
AB  - A peptide screened from a combinatorial peptide library with the sequence
      EYKSWEYC performed best as a ligand for affinity chromatography of human blood
      coagulation factor VIII (FVIII). With this peptide immobilized on monolithic CIM
      columns via epoxy groups we were able to capture FVIII from diluted plasma.
      Rational substitution of amino acids by spot synthesis revealed that lysine and
      cysteine can be exchanged for almost all other proteinogenic amino acids without
      loss of affinity to FVIII. This offers the possibility of site-specific
      attachment via either one of these residues or the N- or C-terminus. The
      aliphatic positions O5 (tryptophan) and O7 (tyrosine), together with the charged
      position O6 (glutamic acid), seem to form the core of the binding unit. In the
      positions with aliphatic amino acids, substitution by tyrosine or phenylalanine,
      and in the positions with charged amino acids, substitution by aspartic acid or
      lysine, preserved the affinity to FVIII. The functionality of the selected
      peptides was confirmed by affinity chromatography. Selective binding and elution
      could be achieved.

PMID- 11972752
TI  - Synthesis and conformational analysis of a coumarinic acid-based cyclic prodrug
      of an opioid peptide with modified sensitivity to esterase-catalyzed
      bioconversion.
AB  - The coumarinic acid-based cyclic DADLE (H-Tyr-D-Ala-Gly-Phe-D-Leu-OH) prodrug 1a
      exhibited more favorable physicochemical properties than did DADLE for permeation
      across the intestinal mucosa. However, prodrug 1a, whose bioconversion to DADLE
      was slow, was subject to extensive biliary clearance when administered to rats in
      vivo. To increase the rate of esterase-catalyzed bioconversion of prodrug 1a,
      thus decreasing its biliary clearance, the oxymethyl-modified prodrug 1, in which
      an aldehyde equivalent is inserted between the phenolic group of the promoiety
      and the carboxylic acid group of the peptide, was synthesized from benzofuran-2
      carboxylic acid 16 via a nine-step procedure. Briefly, phenacyl-protected 3-(2
      hydroxyphenyl)-propynoic acid 17 was coupled with Boc-d-Leu-OCH(2)I 5 to give the
      intermediate 18, which was further elaborated and conjugated with tetrapeptide 4
      to give linear precursor 2. Precursor 2 was then deprotected and cyclized to
      obtain compound 1 using a high dilution technique. In an attempt to investigate
      the effect of the physicochemical properties and the conformation of prodrug 1 on
      its permeation characteristics, we calculated its physicochemical parameters and
      determined its solution conformation using spectroscopic techniques (CD and NMR)
      and molecular dynamics simulations. Prodrug 1 showed a cLogP value and a
      molecular size similar to that of prodrug 1a. The deconvoluted CD spectra
      indicated that prodrug 1 has more random component (71%) than prodrug 1a (42%).
      2D-NMR studies of prodrug 1 showed no signals for amide-amide hydrogen
      interactions and few ROE cross-peaks in ROESY spectra. Using distance restraints
      constructed from ROESY spectra, molecular dynamics simulations of prodrug 1
      generated five conformation families. One family satisfied most of the distance
      restraints and all of the dihedral angles measured by NMR coupling constants. In
      summary, prodrug 1 showed favorable physicochemical properties for permeation of
      the intestinal mucosa. Prodrug 1 adopted a more random conformation in solution
      than prodrug 1a. These differences in solution conformation could affect the
      permeation of the prodrugs across the intestinal mucosa by passive diffusion
      and/or their ability to interact with efflux transporter(s) that would limit
      their transcellular permeation.

PMID- 11972753
TI  - Molecular identification of prey in predator diets.
AB  - In many situations prey choice by predators in the field cannot be established or
      quantified using direct observation. The remains of some prey may be visually
      identified in the guts and faeces of predators but not all predators ingest such
      hard remains and even those that do consume them may also ingest soft-bodies prey
      that leave no recognizable remnants. The result is, at best, a biased picture of
      prey choice. A range of molecular techniques and applications are reviewed that
      allow prey remains to be identified, often to the species and even stage level.
      These techniques, all of which are still in use, include enzyme electrophoresis,
      a range of immunological approaches using polyclonal and monoclonal antibodies to
      detect protein epitopes, and recently developed polymerase chain reaction (PCR)
      based methods for detecting prey DNA. Analyses may be postmortem, on invertebrate
      and vertebrate predators collected from the field, or noninvasive assays of the
      remains in regurgitated bird pellets or vertebrate faeces. It was concluded that
      although monoclonal antibodies are currently the most effective method in use
      today, PCR-based techniques have proved to be highly effective and versatile in
      recent laboratory trials and are likely to rapidly displace all other approaches.

PMID- 11972754
TI  - Genetic variation across the historical range of the wild turkey (Meleagris
      gallopavo).
AB  - Genetic differences within and among naturally occurring populations of wild
      turkeys (Meleagris gallopavo) were characterized across five subspecies'
      historical ranges using amplified fragment length polymorphism (AFLP) analysis,
      microsatellite loci and mitochondrial control region sequencing. Current
      subspecific designations based on morphological traits were generally supported
      by these analyses, with the exception of the eastern (M. g. silvestris) and
      Florida (M. g. osceola) subspecies, which consistently formed a single unit. The
      Gould's subspecies was both the most genetically divergent and the least
      genetically diverse of the subspecies. These genetic patterns were consistent
      with current and historical patterns of habitat continuity. Merriam's populations
      showed a positive association between genetic and geographical distance, Rio
      Grande populations showed a weaker association and the eastern populations showed
      none, suggesting differing demographic forces at work in these subspecies. We
      recommend managing turkeys to maintain subspecies integrity, while recognizing
      the importance of maintaining regional population structure that may reflect
      important adaptive variation.

PMID- 11972755
TI  - Sharp genetic breaks among populations of Haptosquilla pulchella (Stomatopoda)
      indicate limits to larval transport: patterns, causes, and consequences.
AB  - To help stem the precipitous decline of coral reef ecosystems world-wide,
      conservation efforts are focused on establishing interconnected reserve networks
      to protect threatened populations. Because many coral reef organisms have a
      planktonic or pelagic larval dispersal phase, it is critical to understand the
      patterns of ecological connectivity between reserve populations that result from
      larval dispersal. We used genetics to infer dispersal patterns among 24 Indo-West
      Pacific populations of the mantis shrimp, Haptosquilla pulchella. Contrary to
      predictions of high dispersal facilitated by the strong currents of the
      Indonesian throughflow, mitochondrial DNA sequences from 393 individuals
      displayed striking patterns of regional genetic differentiation concordant with
      ocean basins isolated during periods of lowered sea level. Patterns of genetic
      structuring indicate that although dispersal within geographical regions with
      semicontiguous coastlines spanning thousands of kilometres may be common,
      ecologically meaningful connections can be rare among populations separated by as
      little as 300 km of open ocean. Strong genetic mosaics in a species with high
      dispersal potential highlight the utility of genetics for identifying regional
      patterns of genetic connectivity between marine populations and show that the
      assumption that ocean currents will provide ecological connectivity among marine
      populations must be empirically tested in the design of marine reserve networks.

PMID- 11972756
TI  - Patterns of genetic diversity and biogeographical history of the tropical wetland
      tree, Pterocarpus officinalis (Jacq.), in the Caribbean basin.
AB  - Studies examining intraspecific variation in plant species with widespread
      distributions and disjunct populations have mainly concentrated on temperate
      species. Here, we determined the genetic structure of a broadly distributed
      wetland tropical tree, Pterocarpus officinalis (Jacq.), from eight Neotropical
      populations using amplified length fragment polymorphisms (AFLP). AFLPs proved
      highly variable with almost half (48%) of the genetic variation at these loci
      occurring among individuals within populations. Nonetheless, there was a strong
      geographical pattern in the distribution of AFLP variation within P. officinalis.
      Caribbean and continental populations fell into two well-defined genetic clusters
      supported by the presence of a number of unique AFLP bands. Within these two
      regions, there were also strong genetic differences among populations, caused
      mainly by frequency differences in AFLP bands, making it difficult to determine
      the evolutionary relationships among populations. In addition, our analysis of P.
      officinalis revealed striking differences in the levels of AFLP variation among
      the eight populations sampled. In general, Caribbean populations had lower
      genetic diversity than continental populations. Moreover, there was a clear loss
      in AFLP diversity with distance from the continent among Caribbean populations.
      The overall genetic pattern within P. officinalis suggests that past colonization
      history, coupled with genetic drift within local populations, rather than
      contemporary gene flow are the major forces shaping variation within this
      species.

PMID- 11972757
TI  - Genetic diversity and differentiation of Kermode bear populations.
AB  - The Kermode bear is a white phase of the North American black bear that occurs in
      low to moderate frequency on British Columbia's mid-coast. To investigate the
      genetic uniqueness of populations containing the white phase, and to ascertain
      levels of gene flow among populations, we surveyed 10 highly polymorphic
      microsatellite loci, assayed from trapped bear hairs. A total of 216 unique bear
      genotypes, 18 of which were white, was sampled among 12 localities. Island
      populations, where Kermodes are most frequent, show approximately 4% less
      diversity than mainland populations, and the island richest in white bears
      (Gribbell) exhibited substantial genetic isolation, with a mean pairwise FST of
      0.14 with other localities. Among all localities, FST for the molecular variant
      underlying the coat-colour difference (A893G) was 0.223, which falls into the
      95th percentile of the distribution of FST values among microsatellite alleles,
      suggestive of greater differentiation for coat colour than expected under
      neutrality. Control-region sequences confirm that Kermode bears are part of a
      coastal or western lineage of black bears whose existence predates the Wisconsin
      glaciation, but microsatellite variation gave no evidence of past population
      expansion. We conclude that Kermodism was established and is maintained in
      populations by a combination of genetic isolation and somewhat reduced population
      sizes in insular habitat, with the possible contribution of selective pressure
      and/or nonrandom mating.

PMID- 11972758
TI  - Insights into recently fragmented vole populations from combined genetic and
      demographic data.
AB  - We combined demographic and genetic data to evaluate the effects of habitat
      fragmentation on the population structure of the California red-backed vole
      (Clethrionomys californicus). We analysed variation in the mitochondrial DNA
      (mtDNA) control region and five nuclear microsatellite loci in small samples
      collected from two forest fragments and an unfragmented control site in 1990-91.
      We intensively sampled the same forest fragments and two different control sites
      in 1998 and 1999. Vole abundances fluctuated greatly at sizes below 50
      individuals per fragment. Fragment populations had significantly lower mtDNA
      allelic diversity than controls, but not nuclear heterozygosity or numbers of
      alleles. The use of only trapping and/or mtDNA marker data would imply that
      fragment populations are at least partially isolated and vulnerable to inbreeding
      depression. In contrast, the abundance estimates combined with microsatellite
      data show that small fragment populations must be linked to nearby forests by
      high rates of migration. These results provide evidence for the usefulness of
      combining genetic and demographic data to understand nonequilibrium population
      structure in recently fragmented habitats.

PMID- 11972759
TI  - Genetic architecture of sexual and asexual populations of the aphid Rhopalosiphum
      padi based on allozyme and microsatellite markers.
AB  - Cyclical parthenogens, including aphids, are attractive models for comparing the
      genetic outcomes of sexual and asexual reproduction, which determine their
      respective evolutionary advantages. In this study, we examined how reproductive
      mode shapes genetic structure of sexual (cyclically parthenogenetic) and asexual
      (obligately parthenogenetic) populations of the aphid Rhopalosiphum padi by
      comparing microsatellite and allozyme data sets. Allozymes showed little
      polymorphism, confirming earlier studies with these markers. In contrast,
      microsatellite loci were highly polymorphic and showed patterns very discordant
      from allozyme loci. In particular, microsatellites revealed strong heterozygote
      excess in asexual populations, whereas allozymes showed heterozygote deficits.
      Various hypotheses are explored that could account for the conflicting results of
      these two types of genetic markers. A strong differentiation between reproductive
      modes was found with both types of markers. Microsatellites indicated that sexual
      populations have high allelic polymorphism and heterozygote deficits (possibly
      because of population subdivision, inbreeding or selection). Little geographical
      differentiation was found among sexual populations confirming the large dispersal
      ability of this aphid. In contrast, asexual populations showed less allelic
      polymorphism but high heterozygosity at most loci. Two alternative hypotheses are
      proposed to explain this heterozygosity excess: allele sequence divergence during
      long-term asexuality or hybrid origin of asexual lineages. Clonal diversity of
      asexual lineages of R. padi was substantial suggesting that they could have
      frozen genetic diversity from the pool of sexual lineages. Several widespread
      asexual genotypes were found to persist through time, as already seen in other
      aphid species, a feature seemingly consistent with the general-purpose genotype
      hypothesis.

PMID- 11972760
TI  - Evidence of low gene flow in a neotropical clustered tree species in two
      rainforest stands of French Guiana.
AB  - The spatial genetic structure of the neotropical, clustered tree species
      Vouacapoua americana (Aublet) was studied in two natural forest stands (Paracou
      and Nouragues) in French Guiana. Using eight microsatellite loci, V. americana is
      characterized by a marked genetic structure at small spatial distances (under 30
      60 m), in agreement with the limited seed dispersal by rodent species. Gene flow
      through pollen is also shown to be mainly restricted to less than 100 m. This
      result suggests that most pollination events (mediated through small insects) are
      probably limited to within-patches of individuals, which might explain the high
      genetic differentiation among patches (F(ST) = 0.11) separated by less than 2 km.
      We also assume that stronger genetic structure in Paracou is likely to be due to
      lower seed dispersal by rodents, large spatial distances separating patches, or a
      recent recolonization event.

PMID- 11972761
TI  - Reconstructing recent divergence: evaluating nonequilibrium population structure
      in New Zealand chinook salmon.
AB  - Newly established or perturbed populations are often the focus of conservation
      concerns but they pose special challenges for population genetics because drift
      migration equilibrium is unlikely. To advance our understanding of the evolution
      of such populations, we investigated structure and gene flow among populations of
      chinook salmon that formed via natural straying following introduction to New
      Zealand in the early 1900s. We examined 11 microsatellite loci from samples
      collected in several sites and years to address two questions: (i) what
      population differentiation has arisen in the approximately 30 generations since
      salmon were introduced to New Zealand, relative to temporal variation within
      populations; and (ii) what are the approximate effective population sizes and
      amounts of gene flow in these populations? These questions are routinely
      addressed in studies of indigenous populations, but less often in the case of new
      populations and rarely with consideration of equilibrium assumptions. We show
      that despite the recent introduction, continued gene flow and high temporal
      variability among samples, detectable population structure has arisen among the
      New Zealand populations, consistent with their colonization pattern and isolation
      by geographical distance. Furthermore, we use simple individual-based simulations
      and estimates of effective population sizes to estimate the effective gene flow
      among drainages under likely nonequilibrium conditions. Similar methodology may
      be broadly applicable to other studies of population structure and phenotypic
      evolution under similar nonequilibrium, high gene flow conditions.

PMID- 11972762
TI  - Mitochondrial DNA variation in a species with two mitochondrial genomes: the case
      of Mytilus galloprovincialis from the Atlantic, the Mediterranean and the Black
      Sea.
AB  - We have examined mitochondrial DNA (mtDNA) variation in samples of the mussel
      Mytilus galloprovincialis from the Black Sea, the Mediterranean and the Spanish
      Atlantic coast by scoring for presence or absence of cleavage at 20 restriction
      sites of a fragment of the COIII gene and at four restriction sites of the 16S
      RNA gene. This species contains two types of mtDNA genomes, one that is
      transmitted maternally (the F type) and one that is transmitted paternally (the M
      type). The M genome evolves at a higher rate than the F genome. Normally, females
      are homoplasmic for an F type and males are heteroplasmic for an F and an M type.
      Occasionally molecules from the F lineage invade the paternal transmission route,
      resulting in males that carry two F-type mtDNA genomes. These features of the
      mussel mtDNA system give rise to a new set of questions when using mtDNA
      variation in population studies and phylogeny. We show here that the two mtDNA
      types provide different information with regard to amounts of variation and
      genetic distances among populations. The F genome exhibits higher degrees of
      diversity within populations, while the M genome produces higher degrees of
      differentiation among populations. There is a strong differentiation between the
      Atlantic and the Black Sea. The Mediterranean samples have intermediate haplotype
      frequencies, yet are much closer to the Black Sea than to the Atlantic. We
      conclude that in this species gene flow among the three Seas is restricted and
      not enough to erase the combined effect of mutation and random drift. In one
      sample, that from the Black Sea, the majority of males did not contain an M mtDNA
      type. This suggests that a molecule of the maternal lineage has recently invaded
      the paternal route and has increased its frequency in the population to the point
      that the present pool of paternally transmitted mtDNA molecules is highly
      heterogeneous and cannot be used to read the population's history. This liability
      of the paternal route means that in species with doubly uniparental inheritance,
      the maternal lineage provides more reliable information for population and
      phylogenetic studies.

PMID- 11972763
TI  - Statistical properties of population differentiation estimators under stepwise
      mutation in a finite island model.
AB  - Microsatellite loci mutate at an extremely high rate and are generally thought to
      evolve through a stepwise mutation model. Several differentiation statistics
      taking into account the particular mutation scheme of the microsatellite have
      been proposed. The most commonly used is R(ST) which is independent of the
      mutation rate under a generalized stepwise mutation model. F(ST) and R(ST) are
      commonly reported in the literature, but often differ widely. Here we compare
      their statistical performances using individual-based simulations of a finite
      island model. The simulations were run under different levels of gene flow,
      mutation rates, population number and sizes. In addition to the per locus
      statistical properties, we compare two ways of combining R(ST) over loci. Our
      simulations show that even under a strict stepwise mutation model, no statistic
      is best overall. All estimators suffer to different extents from large bias and
      variance. While R(ST) better reflects population differentiation in populations
      characterized by very low gene-exchange, F(ST) gives better estimates in cases of
      high levels of gene flow. The number of loci sampled (12, 24, or 96) has only a
      minor effect on the relative performance of the estimators under study. For all
      estimators there is a striking effect of the number of samples, with the
      differentiation estimates showing very odd distributions for two samples.

PMID- 11972764
TI  - Phylogeographical structure, postglacial recolonization and barriers to gene flow
      in the distinctive Valais chromosome race of the common shrew (Sorex araneus).
AB  - Using one male-inherited and eight biparentally inherited microsatellite markers,
      we investigate the population genetic structure of the Valais chromosome race of
      the common shrew (Sorex araneus) in the Central Alps of Europe. Unexpectedly, the
      Y-chromosome microsatellite suggests nearly complete absence of male gene flow
      among populations from the St-Bernard and Simplon regions (Switzerland).
      Autosomal markers also show significant genetic structuring among these two
      geographical areas. Isolation by distance is significant and possible barriers to
      gene flow exist in the study area. Two different approaches are used to better
      understand the geographical patterns and the causes of this structuring. Using a
      principal component analysis for which testing procedure exists, and partial
      Mantel tests, we show that the St-Bernard pass does not represent a significant
      barrier to gene flow although it culminates at 2469 m, close to the highest
      altitudinal record for this species. Similar results are found for the Simplon
      pass, indicating that both passes represented potential postglacial
      recolonization routes into Switzerland from Italian refugia after the last
      Pleistocene glaciations. In contrast with the weak effect of these mountain
      passes, the Rhone valley lowlands significantly reduce gene flow in this species.
      Natural obstacles (the large Rhone river) and unsuitable habitats (dry slopes)
      are both present in the valley. Moreover, anthropogenic changes to landscape
      structures are likely to have strongly reduced available habitats for this shrew
      in the lowlands, thereby promoting genetic differentiation of populations found
      on opposite sides of the Rhone valley.

PMID- 11972765
TI  - Phylogeography of endemic ermine (Mustela erminea) in southeast Alaska.
AB  - The North Pacific Coast (NPC) of North America is a region of high mammalian
      endemism, possibly due to its highly fragmented landscape and complex glacial
      history. For example, four island and one mainland subspecies of ermine, Mustela
      erminea, have been described as endemic to southeast Alaska alone. To better
      understand the role of past climatic change in generating diversity in the
      region, we examined DNA sequence variation in the mitochondrial cytochrome b gene
      of 210 ermine from across North America, with an emphasis on Alaska and British
      Columbia. We found three distinct (1.5-3.6% uncorrected 'p') lineages of ermine,
      all of which occur in southeast Alaska. One lineage includes a southeast Alaska
      endemic and specimens from Alaska (outside of southeast) and Eurasia. A second
      lineage includes two southeast Alaskan endemics and ermine from western Canada
      and the coterminous United States. The close relationships of these purported
      endemics to ermine outside of southeast Alaska suggest that they colonized the
      region from Beringian and southern glacial refugia, respectively, following
      deglaciation of the NPC. The third lineage appears restricted to the Prince of
      Wales Island complex in southeast Alaska (two subspecies) and Graham Island
      (Haida Gwaii), British Columbia. This restricted distribution suggests that these
      populations may be derived from relicts that persisted in a coastal refugium
      during the Wisconsin glaciation. Studies of nuclear genes and adaptive
      morphological evolution are necessary to further explore discrepancies between
      the geographical pattern of differentiation based on mtDNA and the existing
      subspecific taxonomy based on morphology.

PMID- 11972766
TI  - Using nested clade analysis to assess the history of colonization and the
      persistence of populations of an Iberian Lizard.
AB  - The distribution of the lizard Lacerta schreiberi is likely to have been severely
      affected by the climatic cycles that have influenced the Iberian Peninsula.
      Information about the species ecology and Iberian physiogeography was used to
      generate specific hypotheses about episodes of colonization and subsequent
      population persistence. These hypotheses generated predictions about the
      distribution of genetic variation, which were tested using nested clade analysis
      (NCA) supplemented by analysis of molecular variance (amova). Two predictions
      were confirmed by NCA; that is those that specified multiple and allopatric
      refugia. However, the remaining three predictions were not corroborated by the
      analyses. Firstly, a simple analysis of the distribution of genetic variability
      failed to detect an expected difference in the pattern of colonization between
      the inland mountain system and the coastal region. Moreover, while NCA did detect
      the expected genetic pattern in southern coastal populations, it was explained in
      terms of long-distance migration, which seems implausible because of the extent
      of unsuitable habitat. A more likely cause of the pattern is population
      fragmentation and a reduction in population size caused during the Holocene.
      Finally, NCA also failed to detect a northwestern population expansion, which is
      supported by other evidence. We conclude that NCA has a limited ability to detect
      range expansion led by individuals with more ancestral (interior) haplotypes.

PMID- 11972767
TI  - Transgenic potatoes with enhanced levels of nematode resistance do not have
      altered susceptibility to nontarget aphids.
AB  - Cysteine proteinase inhibitors (cystatins) confer resistance to plant-parasitic
      nematodes when expressed in transgenic plants. The survival and growth of nymphs
      of the peach-potato aphid, Myzus persicae, were adversely affected when cystatins
      were added to artificial diets. When aphids were clip-caged onto transgenic
      plants expressing chicken egg white cystatin (CEWc) there was no adverse effect
      on aphid fitness. Field populations of aphids on transgenic Desiree potatoes,
      expressing CEWc or a modified version of oryzacystatin I, were not significantly
      different from populations on control Desiree plants. The effect of other
      nematode management options on aphid numbers was also studied. A conventionally
      bred cultivar, with partial nematode resistance, supported higher populations of
      aphids than the transgenic lines at the beginning of the sampling period. Peak
      aphid densities on the untreated control and untreated transgenic lines were 7
      and 5.2 aphids per plant. Aldicarb, commonly used to control nematodes on
      potatoes, reduced the value to less than 0.2 aphids per plant. The results
      demonstrate that levels of expression in the plant tissue actually consumed are
      important in determining the risk of cystatins to nontarget invertebrates. The
      study also highlights the importance of including currently used management
      options in any assessment of the impact of transgenic plants on nontarget
      organisms.

PMID- 11972768
TI  - Reconciling genetic expectations from host specificity with historical population
      dynamics in an avian brood parasite, Horsfield's Bronze-Cuckoo Chalcites basalis
      of Australia.
AB  - Mitochondrial DNA (mtDNA) is being used increasingly to explore the evolution of
      host specificity in avian brood parasites. A stable coevolutionary equilibrium
      between multiple phylogenetically unrelated hosts and a brood parasitic species
      predicts that mtDNA diversity in the parasite should be relatively deep and
      phylogenetically structured. Also, the different intraspecific clades resulting
      from parasitism to multiple sympatric hosts should themselves occur
      sympatrically. However, mtDNA diversity in brood parasites is as susceptible to
      effects of historical population dynamics as in any species. We demonstrate the
      relevance of these dynamics to the use of mtDNA in understanding coevolution
      between an Australian brood-parasite, Horsfield's Bronze-Cuckoo Chalcites basalis
      and its hosts, Malurus fairy-wrens and Acanthiza thornbills. Previous ecological
      and behavioural analyses argue that Malurus- and Acanthiza-specific host races
      exist in C. basalis. Yet mtDNA diversity in C. basalis is low and
      phylogenetically unstructured (mean sequence divergence 0.15 +/- 0.07%, range
      0.00%-0.31%) and tests of mtDNA neutrality and range expansion vs. population
      stability (Tajima's D, Fu & Li's F* and D*, Fu's F(S), mismatch analyses) all
      indicate that C. basalis has expanded its range very recently, probably within
      the last few tens of thousands of years following climatic amelioration after a
      peak of aridity in the late Pleistocene. The low mtDNA diversity and its lack of
      phylogenetic structure in C. basalis deny the existence of evolutionarily long
      term stable host races in C. basalis but not the possibility of recently evolved
      ones. They highlight the need for renewed behavioural and ecological study of the
      relationship between C. basalis and its hosts. Our findings illustrate the need
      to understand the evolutionary context in which a brood parasite and its hosts
      have evolved if mtDNA data are to be used in testing hypotheses concerning the
      origin and maintenance of host specificity. They also add to the growing body of
      work illustrating the use of mismatch analyses and Fu's F(S) in detecting range
      expansions.

PMID- 11972769
TI  - Molecular barcodes for soil nematode identification.
AB  - Using a molecular barcode, derived from single-specimen polymerase chain reaction
      (PCR) and sequencing of the 5' segment of the small subunit ribosomal RNA (SSU)
      gene, we have developed a molecular operational taxonomic unit (MOTU) scheme for
      soil nematodes. Individual specimens were considered to belong to the same MOTU
      when the sequenced segment of 450 bases was > 99.5% identical. A Scottish upland
      Agrostis-Festuca grassland soil was sampled, using both culture-based and random
      selection methods. One hundred and sixty-six cultured isolates were sequenced,
      and clustered into five MOTU. From 74 randomly sampled individuals across the
      study site, 19 MOTU were defined. A subsequent sample of 18 individuals from a
      single subplot contained eight MOTU, four of which were unique to the single
      subplot sample. Interestingly, seven of these MOTU were not present in the
      culture-independent sampling. Overall, a total of 23 MOTU were defined from only
      240 sequences. Many MOTU could readily be assigned to classical, morphologically
      defined taxonomic units using a database of SSU sequences from named nematode
      species. The MOTU technique allows a rapid assessment of nematode taxon diversity
      in soils. Correlation with a database of sequences from known species offers a
      route to application of the technique in ecological surveys addressing biological
      as well as genetic diversity.

PMID- 11972770
TI  - A DNA test to sex ratite birds.
AB  - DNA-based sex tests now exist for many avian species. However, none of these
      tests are widely applicable to ratites. We present DNA sequence data for a locus
      that is W chromosome-linked in the kiwi, ostrich, cassowary, rhea, and emu. At
      the amino acid level, this sequence has significant homology to X-linked genes in
      platyfish and Caenorhabditis elegans. Polymerase chain reaction (PCR) primers
      designed to this locus allow the assignment of sex in all species of living
      ratites.

PMID- 11972771
TI  - Diversity in the serine recombinases.
AB  - Most site-specific recombinases fall into one of two families, based on
      evolutionary and mechanistic relatedness. These are the tyrosine recombinases or
      lambda integrase family and the serine recombinases or resolvase/invertase
      family. The tyrosine recombinases are structurally diverse and functionally
      versatile and include integrases, resolvases, invertases and transposases. Recent
      studies have revealed that the serine recombinase family is equally versatile and
      members have a variety of structural forms. The archetypal resolvase/invertases
      are highly regulated, only affect resolution or inversion and they have an N
      terminal catalytic domain and a C-terminal DNA binding domain. Phage-encoded
      serine recombinases (e.g. phiC31 integrase) cause integration and excision with
      strictly controlled directionality, and have an N-terminal catalytic domain but
      much longer C-terminal domains compared with the resolvase/invertases. This high
      molecular weight group also contains transposases (e.g. TnpX from Tn4451). Other
      transposases, which belong to a third structurally different group, are similar
      in size to the resolvase/invertases but have the DNA binding domain N-terminal to
      the catalytic domain (e.g. IS607 transposase). These three structural groups
      represented by the resolvase/invertases, the large serine recombinases and
      relatives of IS607 transposase correlate with three major groupings seen in a
      phylogeny of the catalytic domains. These observations indicate that the serine
      recombinases are modular and that fusion of the catalytic domain to unrelated
      sequences has generated structural and functional diversity.

PMID- 11972772
TI  - Yeast Rio1p is the founding member of a novel subfamily of protein serine kinases
      involved in the control of cell cycle progression.
AB  - Rio1p was identified as a protein serine kinase founding a novel subfamily. It is
      highly conserved from Archaea to man and only distantly related to previously
      established protein kinase families. Nevertheless, analysis of multiple protein
      sequence alignments shows that those amino acid residues that are important for
      either structure or catalytic activity in conventional protein kinases are also
      conserved in members of the Rio1p family at the respective positions
      (corresponding to domains I-XI of protein kinases). Recombinant Rio1p from
      Escherichia coli and tagged Rio1p from yeast has kinase activity in vitro, and
      mutation of amino acid residues that are conserved and indispensable for
      catalytic activity (i.e. ATP-binding motif, catalytic centre) abrogates activity.
      RIO1 is essential in yeast and plays a role in cell cycle progression. After
      sporulation of RIO1/rio1 diploids, RIO1-disrupted progeny cease growth after one
      to three cell divisions and arrest as either large unbudded or large-budded
      cells. Cells deprived of Rio1p are enlarged and arrest either in G1 or in mitosis
      mainly with the DNA at the bud neck and short spindles (a phenotype also seen in
      cells carrying a weak allele), suggesting that Rio1p activity is required for at
      least at two steps during the cell division cycle: for entrance into S phase and
      for exit from mitosis. The weak RIO1 allele leads to increased plasmid loss.

PMID- 11972773
TI  - The p21-activated kinase, Shk1, is required for proper regulation of microtubule
      dynamics in the fission yeast, Schizosaccharomyces pombe.
AB  - The p21-activated kinase, Shk1, is required for the proper establishment of cell
      polarity in the fission yeast, Schizosaccharomyces pombe. We showed recently that
      loss of the essential Shk1 inhibitor, Skb15, causes significant spindle defects
      in fission yeast, thus implicating Shk1 as a potential regulator of microtubule
      dynamics. Here, we show that cells deficient in Shk1 function have malformed
      interphase microtubules and mitotic microtubule spindles, are hypersensitive to
      the microtubule-destabilizing drug thiabendazole (TBZ) and cold sensitive for
      growth. TBZ treatment causes a downregulation of Shk1 kinase activity, which
      increases rapidly after release of cells from the drug, thus providing a
      correlation between Shk1 kinase function and active microtubule polymerization.
      Consistent with a role for Shk1 as a regulator of microtubule dynamics, green
      fluorescent protein (GFP)-Shk1 fusion proteins localize to interphase
      microtubules and mitotic microtubule spindles, as well as to cell ends and septum
      forming regions of fission yeast cells. We show that loss of Tea1, a cell end-
      and microtubule-localized protein previously implicated as a regulator of
      microtubule dynamics in fission yeast, exacerbates the growth and microtubule
      defects resulting from partial loss of Shk1 and that Shk1 localizes to illicit
      growth tips produced by tea1 mutant cells. Our results demonstrate that Shk1 is
      required for the proper regulation of microtubule dynamics in fission yeast and
      implicate Tea1 as a potential Shk1 regulator.

PMID- 11972774
TI  - C-terminal domains of Listeria monocytogenes bacteriophage murein hydrolases
      determine specific recognition and high-affinity binding to bacterial cell wall
      carbohydrates.
AB  - Listeria monocytogenes phage endolysins Ply118 and Ply500 share a unique
      enzymatic activity and specifically hydrolyse Listeria cells at the completion of
      virus multiplication in order to release progeny phage. With the aim of
      determining the molecular basis for the lytic specificity of these enzymes, we
      have elucidated their domain structure and examined the function of their
      unrelated and unique C-terminal cell wall binding domains (CBDs). Analysis of
      deletion mutants showed that both domains are needed for lytic activity. Fusions
      of CBDs with green fluorescent protein (GFP) demonstrated that the C-terminal 140
      amino acids of Ply500 and the C-terminal 182 residues of Ply118 are necessary and
      sufficient to direct the murein hydrolases to the bacterial cell wall. CBD500 was
      able to target GFP to the surface of Listeria cells belonging to serovar groups
      4, 5 and 6, resulting in an even staining of the entire cell surface. In
      contrast, the CBD118 hybrid bound to a ligand predominantly present at septal
      regions and cell poles, but only on cells of serovars 1/2, 3 and 7. Non-covalent
      binding to surface carbohydrate ligands occurred in a rapid, saturation-dependent
      manner. We measured 4 x 104 and 8 x 104 binding sites for CBD118 and CBD500
      respectively. Surface plasmon resonance analysis revealed unexpected high
      molecular affinity constants for the CBD-ligand interactions, corresponding to
      nanomolar affinities. In conclusion, we show that the CBDs are responsible for
      targeting the phage endolysins to their substrates and function to confer
      recognition specificity on the proteins. As the CBD sequences contain no repeats
      and lack all known sequence motifs for anchoring of proteins to the bacterial
      cell, we conclude that they use unique structural motifs for specific association
      with the surface of Gram-positive bacteria.

PMID- 11972776
TI  - The flagella of enteropathogenic Escherichia coli mediate adherence to epithelial
      cells.
AB  - Enteropathogenic Escherichia coli (EPEC) utilizes a type III protein secretion
      system to target effector molecules into the host cell leading to effacement of
      the intestinal mucosa. This secretion apparatus shares many structural features
      of the flagellar type III export system involved in flagella assembly and
      motility. We report here that fliC insertional mutants constructed in two wild
      type EPEC strains were markedly impaired in adherence and microcolony formation
      on cultured cells. An E. coli K-12 strain harbouring the EPEC H6 fliC gene on a
      plasmid showed discrete adhering clusters on HeLa cells, albeit to less extent
      than the wild-type EPEC strain. Flagella purified from EPEC bound to cultured
      epithelial cells and antiflagella antibodies blocked adherence of several EPEC
      serotypes. We determined that eukaryotic cells in culture stimulate expression of
      flagella by motile and non-motile EPEC. Isogenic strains mutated in perA (a
      transcriptional activator), bfpA (a type IV pilin), luxS (a quorum-sensing
      autoinducer gene) and in the type III secretion genes were reduced for motility
      in Dulbecco's modified Eagle medium (DMEM) motility agar and produced none or few
      flagella when associated with epithelial cells. Growth of these mutants in
      preconditioned tissue culture medium restored motility and their ability to
      produce flagella, suggesting the influence of a signal provided by mammalian
      cells that triggers flagella production. This study shows for the first time that
      the flagella of EPEC are directly involved in the adherence of these bacteria and
      supports the existence of a molecular relationship between the two existing type
      III secretion pathways of EPEC, the EPEC adherence factor (EAF) plasmid-encoded
      regulator, quorum sensing and epithelial cells.

PMID- 11972775
TI  - Generation of Campylobacter jejuni genetic diversity in vivo.
AB  - Molecular epidemiology studies suggest that horizontal genetic exchange is a
      major cause of pathogen biodiversity. We tested this concept for the bacterial
      enteropathogen Campylobacter jejuni by seeking direct in vivo evidence for the
      exchange of genetic material among Campylobacter strains. For this purpose, two
      antibiotic resistance markers were inserted into the hipO or htrA gene of
      genetically distinct and naturally transformable C. jejuni strains. Genetic
      exchange of the resistance markers was analysed after co-cultivation of
      homologous and heterologous strains in vitro and in vivo during experimental
      infection of chickens. Double-resistant recombinants were obtained both in vitro
      and from the chicken intestine for all combinations of strains tested.
      Bidirectional genetic exchange of DNA between homologous and heterologous strains
      was confirmed by Southern blotting in combination with flaA polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP), amplified fragment
      length polymorphism (AFLP) and pulsed field gel electrophoresis (PFGE). Extensive
      PFGE analyses of isolated recombinants indicated the frequent occurrence of
      genetic rearrangements during the experimental infection, in addition to the
      homologous recombination of the antibiotic resistance genes. Together, the data
      indicate unequivocally that interstrain genetic exchange as well as intragenomic
      alterations do occur in vivo during C. jejuni infection. These events probably
      explain the genome plasticity observed for this pathogen.

PMID- 11972778
TI  - Involvement of caspase-3-like protein in rapid cell death of Xanthomonas.
AB  - Xanthomonas campestris pv. glycines strain AM2 (XcgAM2), the aetiological agent
      of bacterial pustule disease of soybean, as well as some other strains of
      Xanthomonas including X. campestris pv. malvacearum NCIM 2310 and X. campestris
      NCIM 2961, exhibited post-exponential rapid cell death (RCD) in Luria-Bertani
      (LB) medium. RCD was not displayed by Xanthomonas strains while growing in starch
      medium. Addition of starch to LB culture of XcgAM2 at any point of incubation
      during the exponential growth was found to arrest the onset of RCD. RCD in this
      organism was found to be associated with the synthesis of an endogenous enzyme
      similar to human caspase-3, a known marker of apoptosis in eukaryotes. On sodium
      dodecyl sulphate polyacrylamide gel elecrophoresis (SDS-PAGE) the XcgAM2 caspase
      appeared to run along a 55 kDa protein molecular weight marker. The caspase-3
      like protein was detected in all Xanthomonas strains tested. RCD was not detected
      in Escherichia coli cultures in LB medium. The caspase-3-like enzyme activity or
      pro-tein was also found to be absent in this bacterium. Caspase-3-like protein or
      Xanthomonas caspase was detected only in the cells of XcgAM2 growing in LB medium
      and not in those growing in starch medium. The Xanthomonas caspase protein
      appeared in cells at around 4 h of incubation, and peaked at around 24 h, before
      finally disappearing at around 54 h of incubation. However, caspase enzyme
      activity was detected only 12-13 h after incubation and peaked around 18-20 h.
      Addition of starch at the beginning or during the period of exponential growth in
      LB cultures of XcgAM2 terminated the synthesis of this protein. It is presumed
      that starch acted as the repressor of biosynthesis of the Xanthomonas caspase,
      thereby preventing the organism from undergoing RCD. The cells undergoing RCD
      also displayed the other markers of eukaryotic apoptosis. These included binding
      of annexin V to plasma membrane of cells undergoing RCD and the presence of
      nicked DNA in culture supernatant as evidenced by the TUNEL (terminal
      deoxynucleotidyl transferase dUTP nick-end labelling) assay. Caspase-negative
      mutants of XcgAM2 did not display post-exponential RCD. The importance of RCD in
      Xanthomonas life cycle is not yet clear, however the phenomenon appears to have
      similarities with eukaryotic apoptosis.

PMID- 11972777
TI  - Cytoplasmic dynein intermediate chain and heavy chain are dependent upon each
      other for microtubule end localization in Aspergillus nidulans.
AB  - The multisubunit microtubule motor, cytoplasmic dynein, targets to various
      subcellular locations in eukaryotic cells for various functions. The cytoplasmic
      dynein heavy chain (HC) contains the microtubule binding and ATP binding sites
      for motor function, whereas the intermediate chain (IC) is implicated in the in
      vivo targeting of the HC. Concerning any targeting event, it is not known whether
      the IC has to form a complex with the HC for targeting or whether the IC can
      target to a site independently of the HC. In the filamentous fungus Aspergillus
      nidulans, the dynein HC is localized to the ends of microtubules near the hyphal
      tip. In this study, we demonstrate that our newly identified dynein IC in A.
      nidulans is also localized to microtubule ends and is required for HC's
      localization to microtubule ends in living cells. With the combination of two
      reagents, an HC loss-of function mutant and the green fluorescent protein (GFP)
      fused IC that retains its function, we show that the IC's localization to
      microtubule ends also requires HC, suggesting that cytoplasmic dynein HC-IC
      complex formation is important for microtubule end targeting. In addition, we
      show that the HC localization is not apparently altered in the deletion mutant of
      NUDF, a LIS1-like protein that interacts directly with the ATP-binding domain of
      the HC. Our study suggests that, although HC-IC association is important for the
      targeting of dynein to microtubule ends, other essential components, such as
      NUDF, may interact with the targeted dynein complex to produce full motor
      activities in vivo.

PMID- 11972779
TI  - Dual control of subtilin biosynthesis and immunity in Bacillus subtilis.
AB  - The production of the peptide antibiotic (lantibiotic) subtilin in Bacillus
      subtilis ATCC 6633 is highly regulated. Transcriptional organization and
      regulation of the subtilin gene cluster encompassing 11 genes was characterized.
      Two polycistronic mRNAs encoding transcript spaBTC (6.8 kb) and encoding
      transcript spaIFEG (3.5 kb) as well as the monocistronic spaS (0.3 kb) mRNA were
      shown by Northern hybridization. Primer extension experiments and beta
      galactosidase fusions confirmed three independent promoter sites preceding genes
      spaB, spaS and spaI. beta-Galactosidase expression of spaB, spaS and spaI
      promoter lacZ fusions initiated in mid-exponential growth. Maximal activities
      were reached at the transition to stationary growth and were collinear with
      subtilin production. The lacZ activity was dependent on co-expression with the
      two-component regulatory system spaRK. The presence of subtilin was needed for
      efficient expression of all three promoter lacZ fusions. This suggests a
      transcriptional autoregulation according to a quorum-sensing mechanism with
      subtilin as autoinducer and signal transduction via SpaRK. Additionally, spaR
      expression was found to be under positive control of the alternative sigma factor
      H. Deletion of sigma H strongly decreased subtilin production. Full subtilin
      production could be restored after in-trans complementation of spaR. Deletion of
      the major B. subtilis transition state regulator AbrB strongly increased subtilin
      production. These results show that the spaRK two-component regulatory system,
      and hence subtilin biosynthesis and immunity, is under dual control of two
      independent regulatory systems: autoinduction via subtilin and transcriptional
      regulation via sigma factor H.

PMID- 11972780
TI  - StoPK-1, a serine/threonine protein kinase from the glycopeptide antibiotic
      producer Streptomyces toyocaensis NRRL 15009, affects oxidative stress response.
AB  - The glycopeptide antibiotic-producing bacterium, Streptomyces toyocaensis NRRL
      15009, has proteins phosphorylated on Ser, Thr, Tyr and His, implying the
      presence of a battery of associated kinases. We have identified the Ser/Thr
      protein kinase gene fragments stoPK-1, stoPK-2, stoPK-3 and stoPK-4 from S.
      toyocaensis NRRL 15009 by a polymerase chain reaction (PCR) strategy using
      oligonucleotide primers based on eukaryotic Ser/Thr and Tyr kinase sequences. One
      of these (stoPK-1) was subsequently cloned in its entirety from a 3.2 kb genomic
      BamHI fragment. stoPK-1 encodes a 642-amino-acid protein with a predicted N
      terminal Ser/Thr kinase domain and a C-terminal coiled-coil region divided by a
      membrane-spanning region. Expression of StoPK-1 in Escherichia coli yielded a
      protein confined to the membrane fraction, which was found to be phosphorylated
      exclusively on Thr residues and could transfer phosphate to the model substrates
      myelin basic protein and histone H1. Both autophosphorylation and phosphoryl
      transfer could be inhibited by the flavanoid apigenin. Disruption of stoPK-1 with
      the apramycin resistance gene in the S. toyo-caensis chromosome resulted in
      changes in mycelial morphology and an increased sensitivity to the redox cycling
      agents paraquat and nitrofurantoin on glucose-containing media. Supplying stoPK-1
      or the S. coelicolor homologue pkaF in trans could reverse this sensitivity,
      whereas a catalytically inactive mutant of stoPK-1 could not, indicating that
      kinase activity is essential for this phenotype. This suggests a link between
      this membrane-bound protein kinase in signalling pathways sensitive to oxidative
      stress and/or glucose metabolism. These results broaden the roles of Ser/Thr
      protein kinases in bacteria and underscore the diversity of signal transduction
      mechanisms available to respond to various stimuli.

PMID- 11972781
TI  - Characterization of the dihydrolipoamide dehydrogenase from Streptococcus
      pneumoniae and its role in pneumococcal infection.
AB  - In the present study, we have characterized the dihydrolipoamide dehydrogenase
      (DLDH) of Strepto-coccus pneumoniae and its role during pneumococcal infection.
      We have also demonstrated that a lack of DLDH results in a deficiency in alpha
      galactoside metabolism and galactose transport. DLDH is an enzyme that is
      classically involved in the three-step conversion of 2-oxo acids to their
      respective acyl-CoA derivatives, but DLDH has also been shown to have other
      functions. The dldh gene was virtually identical in three pneumococcal strains
      examined. Besides the functional domains and motifs associated with this enzyme,
      analysis of the pneumococcal dldh gene sequence revealed the presence of an N
      terminal lipoyl domain. DLDH-negative bacteria totally lacked DLDH activity,
      indicating that this gene encodes the only DLDH in S. pneumoniae. These DLDH
      negative bacteria grew normally in vitro but were avirulent in sepsis and lung
      infection models in mice, indicating that DLDH activity is necessary for the
      survival of pneumococci within the host. The lack of virulence was not associated
      with a loss of 2-oxo acid dehydrogenase activity, as the wild-type pneumococcal
      strains did not contain activity of any of the known 2-oxo acid enzyme complexes.
      Instead, studies of carbohydrate utilization demonstrated that the DLDH-negative
      bacteria were impaired for alpha-galactoside and galactose metabolism. The DLDH
      mutants lost their ability to oxidize or grow with galactose or melibiose as sole
      carbon source and showed reduced oxidation and growth on raffinose or stachyose.
      The bacteria had an 85% reduction in alpha-galactosidase activity and showed
      virtually no transport of galactose into the cells, which can explain these
      phenotypic changes. The DLDH-negative bacteria produced only 50% of normal
      capsular polysaccharide, a phenotype that may be associated with impaired
      carbohydrate metabolism.

PMID- 11972782
TI  - Mapping the DNA-binding domain and target sequences of the Streptomyces peucetius
      daunorubicin biosynthesis regulatory protein, DnrI.
AB  - Streptomyces antibiotic regulatory proteins (SARPs) constitute a novel family of
      transcriptional activators that control the expression of several diverse anti
      biotic biosynthetic gene clusters. The Streptomyces peucetius DnrI protein, one
      of only a handful of these proteins yet discovered, controls the biosynthesis of
      the polyketide antitumour antibiotics daunorubicin and doxorubicin. Recently,
      comparative analyses have revealed significant similarities among the predicted
      DNA-binding domains of the SARPs and the C-terminal DNA-binding domain of the
      OmpR family of regulatory proteins. Using the crystal structure of the OmpR
      binding domain as a template, DnrI was mapped by truncation and site-directed
      mutagenesis. Several highly conserved residues within the N-terminus are crucial
      for DNA binding and protein function. Tandemly arranged heptameric imperfect
      repeat sequences are found within the -35 promoter regions of target genes.
      Substitutions for each nucleotide within the repeats of the dnrG-dpsABCD promoter
      were performed by site-directed mutagenesis. The mutant promoter fragments were
      found to have modified binding characteristics in gel mobility shift assays. The
      spacing between the repeat target sequences is also critical for successful
      occupation by DnrI and, therefore, competent transcriptional activation of the
      dnrG-dpsABCD operon.

PMID- 11972783
TI  - The FtsH protease is involved in development, stress response and heat shock
      control in Caulobacter crescentus.
AB  - The ftsH gene of Caulobacter crescentus has been isolated and identified as a
      component of the general stress response of this organism. In C. crescentus, ftsH
      expression is transiently induced after temperature upshift and in stationary
      phase. Consistent with this, mutants deprived of the FtsH protease are viable at
      normal growth conditions, but are highly sensitive to elevated temperature,
      increased salt concentration or the presence of antibiotics. Overexpression of
      ftsH resulted in an increased salt but not thermotolerance, emphasizing the
      importance of the FtsH protease in stress response. Mutants lacking FtsH were
      unable to undergo morphological and physiological adaptation in stationary phase
      and, upon starvation, experienced a more pronounced loss of viability than cells
      containing FtsH. In addition, cells lacking FtsH had an increased cellular
      concentration of the heat shock sigma factor sigma32, indicating that, as in
      Escherichia coli, the FtsH protease is involved in the control of the C.
      crescentus heat shock response. In agreement with this, transcription of the heat
      induced sigma32-dependent gene dnaK was derepressed at normal temperature when
      FtsH was absent. In contrast, the groEL gene, which is controlled in response to
      heat stress by both sigma32 and a HcrA/CIRCE mechanism, was not derepressed in an
      ftsH mutant. Finally, FtsH is involved in C. crescentus development and cell
      cycle control. ftsH mutants were unable to synthesize stalks efficiently and had
      a severe cell division phenotype. In the absence of FtsH, swarmer cells
      differentiated into stalked cells faster than when FtsH was present, even though
      the entire cell cycle was longer under these conditions. Thus, directly or
      indirectly, the FtsH protease is involved in the inherent biological clock
      mechanism, which controls the timing of cell differentiation in C. crescentus.

PMID- 11972784
TI  - Role of rubrerythrin in the oxidative stress response of Porphyromonas
      gingivalis.
AB  - Rubrerythrins are non-haem iron proteins that have been implicated in oxidative
      stress protection in anaerobic bacteria and archaea. However, up to now, this
      role has not been confirmed directly by inactivation of a rubrerythrin gene. Here
      we report generation of an rbr- mutant of Porphyromonas gingivalis, an obligately
      anaerobic gingival pathogenic bacterium. Characterization of the rbr- strain
      clearly showed that P. gingivalis produces a rubrerythrin-like protein that is
      absent in the rbr- strain, and that the P. gingivalis rbr- strain is more
      dioxygen- and hydrogen peroxide-sensitive than the wild type. The latter
      conclusion is based on two independent results, namely, deeper no-growth zones
      upon diffusion of the oxidants through soft agar culture tubes and growth
      impairment of liquid cultures exposed to the oxidants. A same-site rbr+ revertant
      showed increased hydrogen peroxide and dioxygen resistance relative to the rbr-
      strain. Transcription of the P. gingivalis rubrerythrin gene is induced above its
      constitutive anaerobic level in response to dioxygen or hydrogen peroxide
      exposures. Purified rubrerythrins from other organisms have been shown to
      catalyse reduction of hydrogen peroxide, while showing relatively sluggish
      reaction with dioxygen and little or no catalase or superoxide dismutase
      activities. Porphyromonas gingivalis contains a superoxide dismutase but lacks
      catalase and haem peroxidases. We therefore suggest that rubrerythrin provides
      oxidative stress protection via catalytic reduction of intracellular hydrogen
      peroxide.

PMID- 11972785
TI  - Genetics of the phage growth limitation (Pgl) system of Streptomyces coelicolor
      A3(2).
AB  - The phage growth limitation (Pgl) system, encoded by Streptomyces coelicolor
      A3(2), confers protection against the temperate bacteriophage phiC31 and its
      homoimmune relatives. The Pgl phenotype is characterized by the ability of Pgl+
      hosts to support a phage burst on initial infection but subsequent cycles are
      severely attenuated. Previously, two adjacent genes pglY and pglZ were shown to
      be required for Pgl. It had been shown by Southern blotting that Streptomyces
      lividans, a close relative of S. coelicolor and naturally Pgl-, does not contain
      homologues of pglYZ and that introduction of pglYZ into S. lividans is not
      sufficient to confer a Pgl+ phenotype. Moreover, the mechanism of the Pgl+<-->
      Pgl- phase variation associated with this phenotype is also not understood. Here
      we describe two novel genes, pglW and pglX, that were shown to be part of this
      system by complementation of Pgl- mutants and by insertional mutagenesis. pglW
      encodes a 169 kDa protein that includes putative motifs for both serine/threonine
      protein kinase activity and DNA binding. pglX encodes a 136 kDa protein with
      putative adenine-specific DNA methyltransferase activity. pglW and pglX have
      overlapping stop-start codons suggesting transcriptional and translational
      coupling. S1 mapping of transcripts initiating up-stream of pglW indicated that,
      like pglYZ, pglWX is expressed in uninfected cultures. A homologue of pglX with
      76% amino acid identity was identified in S. coelicolor, and insertional
      mutagenesis indicated that this gene was not required for the Pgl+ phenotype.
      Southern blots indicated that S. lividans does not contain homologues of pglW or
      pglX. A plasmid encoding pglWXYZ was able to confer the Pgl+ phenotype to S.
      lividans implying that these four genes constitute the whole system.

PMID- 11972786
TI  - Polar localization of the Escherichia coli oriC region is independent of the site
      of replication initiation.
AB  - The location of the origin-linked region of the Escherichia coli chromosome was
      analysed in strains lacking the core origin locus, oriC. In these strains, which
      initiate replication from F factors integrated at different locations around the
      chromosome, origin-linked DNA remains localized near the cell poles, as in wild
      type cells. In contrast, minichromosomes containing 7 kb of chromosomal DNA
      including oriC are generally excluded from the ends of the cell. Thus, we propose
      that positioning of the wild-type origins at the poles is not a function of their
      order of replication but a sequence-specific phenomenon. It is proposed that
      there are centromere-like sequences, bordering the wild-type origin of
      replication, which are used by host mechanisms to direct the proper placement of
      the origin region of the chromosome. This function, combined with other host
      processes, may assure efficient segregation of the E. coli chromosome.

PMID- 11972787
TI  - Competitive interaction of the OxyR DNA-binding protein and the Dam methylase at
      the antigen 43 gene regulatory region in Escherichia coli.
AB  - The antigen 43 surface protein of Escherichia coli is expressed in a phase
      variable manner by a mechanism involving alternative activation and repression of
      transcription of the agn43 gene. The repressor is the OxyR DNA-binding protein,
      and its binding site was found to be located downstream of the agn43
      transcription start site in a region of DNA that encompasses three 5'-GATC-3'
      sequences that are subject to Dam-mediated DNA methylation. It has been suggested
      previously that the phase-variable expression of antigen 43 results from a
      competition between Dam methylase and the OxyR repressor for these sites. The 5'
      GATC-3' sequences were inactivated for methylation by site-directed mutagenesis,
      and all possible combinations of inactive and active sites were assessed for
      effects on phase-variable expression of the agn43 gene. Inactivation of any 5'
      GATC-3' site individually had no effect; at least two sites had to be inactivated
      to disrupt the normal pattern of expression. Studies of OxyR interaction with
      agn43 DNA showed that methylation of any two 5'-GATC-3' sites was necessary and
      sufficient to block binding of the repressor. It was also found that the adenines
      of the second and third 5'-GATC-3' sites are required for OxyR binding,
      demonstrating that the sites for Dam methylation and for repressor binding are
      intimately associated. This is consistent with a competition model in which Dam
      and OxyR share a preference for specific DNA sequences in the regulatory region
      of the agn43 gene.

PMID- 11972788
TI  - Dam-dependent phase variation of Ag43 in Escherichia coli is altered in a seqA
      mutant.
AB  - In Escherichia coli, phase variation of the outer membrane protein Ag43 encoded
      by the agn43 gene is mediated by DNA methylation and the global regulator OxyR.
      Transcription of agn43 occurs (ON phase) when three Dam target sequences in the
      agn43 regulatory region are methylated, which prevents the repressor OxyR from
      binding. Conversely, transcription is repressed (OFF) when these Dam target
      sequences are unmethylated and OxyR binds. A change in expression phase requires
      a concomitant change in the DNA methylation state of these Dam target sequences.
      To gain insight into the process of inheritance of the expression phase and the
      DNA methylation state, protein-DNA interactions at agn43 were examined. Binding
      of OxyR at agn43 was sufficient to protect the three GATC sequences contained
      within its binding site from Dam-dependent methylation in vitro, suggesting that
      no other factors are required to maintain the unmethylated state and OFF phase.
      To maintain the methylated state of the ON phase, however, Dam must access the
      hemimethylated agn43 region after DNA replication, and OxyR binding must not
      occur. OxyR bound hemimethylated agn43 DNA, but the affinity was severalfold
      lower than for unmethylated DNA. This presumably contributes to the maintenance
      of the methylated state but, at the same time, may allow for infrequent OxyR
      binding and a switch to the OFF phase. Hemimethylated agn43 DNA was also a
      binding substrate for the sequestration protein SeqA. Thus, SeqA, OxyR and Dam
      may compete for the same hemimethylated agn43 DNA that is formed after DNA
      replication in an ON phase cell. In isolates with a mutant seqA allele, agn43
      phase variation rates were altered and resulted in a bias to the OFF phase. In
      part, this can be attributed to the observed decrease in the level of DNA
      methylation in the seqA mutant.

PMID- 11972789
TI  - Binding site requirements of the virulence gene regulator AphB: differential
      affinities for the Vibrio cholerae classical and El Tor tcpPH promoters.
AB  - The differential expression of virulence genes be-tween the two disease-causing
      biotypes of Vibrio cholerae, classical and El Tor, is primarily due to a single
      basepair change in the tcpPH promoter, which strongly influences the ability of
      the LysR regulator AphB to activate transcription in response to environmental
      conditions. We show here that this single basepair change influences virulence
      gene expression by dramatically altering the affinity of AphB for its recognition
      site in the tcpPH promoter. AphB binds greater than 10-fold more efficiently to a
      wild-type classical tcpPH promoter fragment with an A at -65 relative to a wild
      type El Tor fragment that has a G at this position. As this single basepair
      change is located within the left arm of the LysR recognition motif (5'-TGCAA-N7
      TTGCA), which extends from -69 to -53, a systematic mutagenesis of the other
      positions within this site was carried out to assess their influence on AphB
      binding in vitro and transcriptional activation in vivo. This analysis revealed
      that the left and right arms of the interrupted dyad display a high degree of
      symmetry with respect to their role in AphB binding. The right promoter proximal
      arm also plays a role in transcriptional activation that is distinct from its
      role in AphB binding. A second AphB binding site (5'-TGCAA-N7-TGTCA) was
      identified upstream of the aphB gene itself, which extends from +17 to +33
      relative to the start of transcription and functions in autorepression. Although
      the sequences of the AphB binding sites at the tcpPH and aphB promoters are
      highly conserved, important differences exist in the way that AphB functions at
      each of these sites.

PMID- 11972790
TI  - RusA proteins from the extreme thermophile Aquifex aeolicus and lactococcal phage
      r1t resolve Holliday junctions.
AB  - The RusA protein of Escherichia coli is a DNA structure-specific endonuclease
      that resolves Holliday junction intermediates formed during DNA replication,
      recombination and repair by introducing symmetrically paired incisions 5' to CC
      dinucleotides. It is encoded by the defective prophage DLP12, which raises the
      possibility that it may be of bacteriophage origin. We show that rusA-like
      sequences are indeed often associated with prophage sequences in the genomes of
      several bacterial species. They are also found in many bacteriophages, including
      Lactococcus lactis phage r1t. However, rusA is also present in the chromosome of
      the hyperthermophilic bacterium Aquifex aeolicus. In this case, there is no
      obvious association of rusA with prophage-like sequences. Given the ancient
      lineage of Aquifex aeolicus, this observation provides the first indication that
      RusA may be of bacterial origin. The RusA proteins of A. aeolicus and
      bacteriophage r1t were purified and shown to resolve Holliday junctions. The r1t
      enzyme also promotes DNA repair in strains lacking the RuvABC resolvase. Both
      enzymes cleave junctions in a sequence-dependent manner, but the A. aeolicus RusA
      shows a different sequence preference (3' to TG) from the E. coli protein (5' to
      CC), and the r1t RusA has relaxed sequence dependence, requiring only a single
      cytosine.

PMID- 11972791
TI  - Mg2+ homeostasis and avoidance of metal toxicity.
AB  - Because Mg2+ is required for a wide variety of cellular functions, its
      intracellular levels must be tightly regulated. In the Gram-negative bacterium
      Salmonella enterica, three transporters mediate Mg2+ uptake: the P-type ATPases
      MgtA and MgtB, whose expression is transcriptionally induced in low Mg2+ by the
      Mg2+-regulated PhoP/PhoQ two-component system; and CorA, whose transcription is
      regulated neither by the levels of Mg2+ nor by the PhoP/PhoQ system. We now
      report that mutants defective in phoP or in both mgtA and mgtB are hypersensitive
      to oxidative stress-dependent Fe (II)-mediated killing. These mutants display
      increased iron accumulation and heightened Ni2+ uptake. Inactivation of the corA
      gene restored Fe(II) resistance to the phoP mutant and eliminated uptake of Ni2+.
      Neither corA transcription nor CorA protein levels were altered in the phoP
      mutant, suggesting that CorA alters its activity in response to the presence of
      PhoP-regulated determinants. Downregulation of CorA activity in low Mg2+
      environments may enable Salmonella to avoid the uncontrolled influx of toxic
      metals.

PMID- 11972792
TI  - Nitrate and the GATA factor AreA are necessary for in vivo binding of NirA, the
      pathway-specific transcriptional activator of Aspergillus nidulans.
AB  - In Aspergillus nidulans, the genes coding for nitrate reductase (niaD) and
      nitrite reductase (niiA), are transcribed divergently from a common promoter
      region of 1200 basepairs. We have previously characterized the relevant cis
      acting elements for the two synergistically acting transcriptional activators
      NirA and AreA. We have further shown that AreA is constitutively bound to a
      central cluster of four GATA sites, and is involved in opening the chromatin
      structure over the promoter region thus making additional cis-acting binding
      sites accessible. Here we show that the asymmetric mode of NirA-DNA interaction
      determined in vitro is also found in vivo. Binding of the NirA transactivator is
      not constitutive as in other binuclear C6-Zn2+-cluster proteins but depends on
      nitrate induction and, additionally, on the presence of a wild-type areA allele.
      Dissecting the role of AreA further, we found that it is required for
      intracellular nitrate accumulation and therefore could indirectly exert its
      effect on NirA via inducer exclusion. We have tested this possibility in a strain
      accumulating nitrate in the absence of areA. We found that in such a strain the
      intracellular presence of inducer is not sufficient to promote either chromatin
      rearrangement or NirA binding, implying that both processes are directly
      dependent on AreA.

PMID- 11972793
TI  - PrnA, a Zn2Cys6 activator with a unique DNA recognition mode, requires inducer
      for in vivo binding.
AB  - The PrnA transcriptional activator of Aspergillus nidulans binds as a dimer to
      CCGG-N-CCGG inverted repeats and to CCGG-6/7N-CCGG direct repeats. The binding
      specificity of the PrnA Zn cluster differs from that of the Gal4p/Ppr1p/UaY/Put3p
      group of proteins. Chimeras with UaY, a protein that strictly recognizes a CGG-6N
      CCG motif, show that the recognition of the direct repeats necessitates the PrnA
      dimerization and linker elements, but the recognition of the CCGG-N-CCGG inverted
      repeats depends crucially on the PrnA Zn binuclear cluster and/or on residues
      amino-terminal to it. Three high-affinity sites in two different promoters have
      been visualized by in vivo methylation protection. Proline induction is essential
      for in vivo binding to these three sites but, as shown previously, not for
      nuclear entry. Simultaneous repression by ammonium and glucose does not affect in
      vivo binding to these high-affinity sites. PrnA differs from the isofunctional
      Saccharomyces cerevisiae protein Put3p, both in its unique binding specificity
      and in the requirement of induction for in vivo DNA binding.

PMID- 11972795
TI  - OLIG-1 and 2 gene expression and oligodendroglial tumours.
AB  - OLIG 1/2 genes encode basic helix-loop-helix transcription factors that play a
      critical role in motor neurone and oligodendrocyte fate specification during
      development. Two recent studies in which OLIG transcripts were detected by in
      situ hybridization have reported a high expression of the OLIG genes in
      oligodendrogliomas. This suggests that the detection of these lineage markers
      could become an adjunct to the classic morphological diagnosis of these tumours.
      There are problems in the diagnosis of oligodendroglioma. To date, all other
      known oligodendrocyte lineage markers have failed to label specifically
      neoplastic oligodendrocytes. Deletions on chromosome 1p and 19q are much more
      frequent in oligodendrogliomas than in astrocytomas but these molecular
      alterations are not constant. For the future, when routinely available,
      immunohistochemical techniques using anti-OLIG antibodies on paraffin embedded
      tissues will allow a systematic study of a large series of tumours so that we
      will know the specificity and sensitivity of this investigation in diagnosis. At
      another level, it is possible that expression of OLIG in neoplastic
      oligodendrocyte might participate in the oncogenesis of oligodendrogliomas.
      Initial work suggests that this is probably not the case. However further in
      vitro and in vivo studies analysing the functional consequence of OLIG
      overexpression in terms of proliferation and tumour progression are needed.

PMID- 11972796
TI  - Cytokines and neurotrophic factors fail to affect Nogo-A mRNA expression in
      differentiated human neurones: implications for inflammation-related axonal
      regeneration in the central nervous system.
AB  - Nogo is a novel myelin-associated inhibitor of neurite outgrowth which regulates
      stable neuronal connections during axonal regeneration following injury in the
      adult mammalian central nervous system (CNS). Because cytokines and neurotrophic
      factors play a key role in inflammation-related axonal regeneration, we
      investigated: (i) the constitutive expression of Nogo and the Nogo receptor (NgR)
      mRNA in human neural cell lines; (ii) Nogo and NgR mRNA levels in the NTera2
      human teratocarcinoma cell line during retinoic acid (RA)-induced neuronal
      differentiation; and (iii) their regulation in NTera2-derived differentiated
      neurones (NTera2-N) after exposure to a battery of cytokines and growth factors
      potentially produced by activated glial cells at post-traumatic inflammatory
      lesions in the CNS. By reverse transcriptase-polymerase chain reaction analysis,
      the constitutive expression of Nogo-A, the longest isoform of three distinct Nogo
      transcripts and NgR mRNA was identified in a wide variety of human neural and non
      neural cell lines. By Northern blot analysis, the levels of Nogo-A mRNA were
      elevated markedly in NTera2 cells following RA-induced neuronal differentiation,
      accompanied by an increased expression of the neurite growth-associated protein
      GAP-43 mRNA. In contrast, Nogo-A, Nogo-B, NgR and GAP-43 mRNA levels were
      unaltered in NTera2-N cells by exposure to basic fibroblast growth factor, brain
      derived neurotrophic factor, glia-derived neurotrophic factor, tumour necrosis
      factor-alpha, interleukin-1beta, dibutyryl cyclic AMP or phorbol 12-myristate 13
      acetate. These results indicate that both Nogo-A and NgR mRNA are coexpressed in
      various human cell types, including differentiated neurones, where their
      expression is unaffected by exposure to a panel of cytokines and neurotrophic
      factors which might be involved in inflammation-related axonal regeneration in
      the CNS.

PMID- 11972797
TI  - Transforming growth factor beta1, the dominant cytokine in murine prion disease:
      influence on inflammatory cytokine synthesis and alteration of vascular
      extracellular matrix.
AB  - Previous studies from our laboratory have shown the ME7 model of murine scrapie
      to be accompanied by an atypical inflammatory response that is characterized by
      marked astroglial and microglial activation but also by the lack of significant
      expression of the pro-inflammatory cytokines interleukin (IL)-1beta and IL-6. The
      aim of this study was to determine whether, in the absence of IL-1beta and IL-6,
      tumour necrosis factor (TNF)-alpha may play an equivalent pro-inflammatory role,
      or if an anti-inflammatory cytokine profile dominates. We have used competitive
      polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) to
      determine the levels of TNF-alpha, IL-10 and transforming growth factor (TGF)
      beta1 in the ME7 model, using their expression in lipopolysaccharide (LPS)
      induced acute inflammation as a positive control. Levels of mRNA were elevated
      for all three cytokines during acute inflammation, while TGF-beta1 mRNA alone was
      significantly elevated in ME7-injected brains. Similarly, by ELISA, we detected
      elevated IL-10, TNF-alpha and TGF-beta1 in LPS-injected animals but only
      significant elevation of TGF-beta1 in ME7-injected animals. An increase in
      laminin and collagen IV deposition around blood vessels was also observed and is
      consistent with up-regulation by active TGF-beta1. These findings suggest that
      TGF-beta1 may play a central role in maintenance of an atypical microglial
      phenotype and may also be involved in vascular and extracellular matrix changes.

PMID- 11972798
TI  - Ubiquitin-only intraneuronal inclusion in the substantia nigra is a
      characteristic feature of motor neurone disease with dementia.
AB  - Two types of ubiquitinated inclusions have been described in motor neurone
      disease (MND). (1) Skein or globular ubiquitinated inclusions in the motor
      neurones (more frequently in the lower motor neurones). This is a characteristic
      feature of all motor neurone disease categories. (2) Dot-shape or crescentric
      ubiquitinated inclusions in the upper layers of cortex and dentate gyrus
      described in cases of motor neurone disease with dementia (DMND). We investigated
      the substantia nigra (SN) in MND cases; two cases of motor neurone disease
      inclusion body (MND-IB) dementia, six cases of DMND, 14 cases of MND (including
      one case from Guam and two cases of familial SOD1 mutation), four cases of
      Parkinson's disease (PD), and 10 cases of age-matched normal controls. SN and
      spinal cord sections were stained with ubiquitin (alpha-synuclein, tau, PGM1, SMI
      31 and SOD1 antibodies). The neuronal density in SN was quantified by using a
      computer-based image analysis system. Four out of six DMND cases showed rounded
      ubiquitin positive inclusions with irregular frayed edges, associated with
      neuronal loss, reactive astrocytosis and a large number of activated microglia
      cells. These inclusions are negative with antibodies to (alpha-synuclein, tau,
      SMI-31 and SOD1). The SN in cases from MND-IB dementia and MND showed occasional
      neuronal loss and no inclusions. The ubiquitin-only inclusions in SN of DMND
      cases are similar (but not identical) to the ubiquitinated inclusions described
      previously in the spinal cord of MND cases and are distinct from Lewy bodies
      (LBs). The degeneration of SN is most likely a primary neurodegenerative process
      of motor neurone disease type frequently involving the DMND cases. MND disease is
      a spectrum and multisystem disorder with DMND located at the extreme end of a
      spectrum affecting the CNS more widely than just the motor system.

PMID- 11972799
TI  - Quantification of vacuolation ("spongiform change"), surviving neurones and prion
      protein deposition in eleven cases of variant Creutzfeldt-Jakob disease.
AB  - Vacuolation ("spongiform change") and prion protein (PrP) deposition were
      quantified in the cerebral cortex, hippocampus, dentate gyrus and molecular layer
      of the cerebellum in 11 cases of variant Creutzfeldt-Jakob disease (vCJD). The
      density of vacuoles was greater in the cerebral cortex compared to the
      hippocampus, dentate gyrus and cerebellum. Within the cortex, vacuole density was
      significantly greater in the occipital compared to the temporal lobe and the
      density of surviving neurones was greatest in the occipital lobe. The density of
      the non-florid PrP plaques was greater in the cerebellum compared to the other
      brain areas. There were significantly more florid-type PrP plaques in the
      cerebral cortex compared to the hippocampus and the molecular layer of the
      cerebellum. No significant correlations were observed between the densities of
      the vacuoles and the PrP plaques. The densities of vacuoles in the parietal
      cortex and the non-florid plaques in the frontal cortex were positively
      correlated with the density of surviving neurones. The densities of the florid
      and the non-florid plaques were positively correlated in the parietal cortex,
      occipital cortex, inferior temporal gyrus and dentate gyrus. The data suggest:
      (i) vacuolation throughout the cerebral cortex, especially in the occipital lobe,
      but less evident in the hippocampus and molecular layer of the cerebellum; (ii)
      the non-florid plaques are more common than the florid plaques and predominate in
      the molecular layer of the cerebellum; and (iii) either the florid plaques
      develop from the non-florid plaques or both types are morphological variants
      resulting from the same degenerative process.

PMID- 11972800
TI  - Human medulloblastomas lack point mutations and homozygous deletions of the
      hSNF5/INI1 tumour suppressor gene.
AB  - Medulloblastomas (MBs) are malignant primitive neuroectodermal tumours (PNETs) of
      the cerebellum occurring predominantly in childhood. The association of monosomy
      of chromosome 22 with MB is controversial. Atypical teratoid/rhabdoid tumours
      (AT/RTs) of the brain share clinical and histological features with MBs and
      supratentorial PNETs (sPNETs). In particular, AT/RTs can be misdiagnosed as MBs
      and sPNETs because AT/RTs frequently contain areas of primitive neuroepithelial
      cells similar to PNETs. Recently, mutations of the tumour suppressor gene
      hSNF5/INI1, located on 22q11.23, have been described in AT/RTs, MBs and sPNETs,
      with conflicting data on the prevalence of hSNF5/INI1 mutations in the latter
      entities. Therefore, we screened MBs for point mutations and homozygous deletions
      of the hSNF5/INI1 tumour suppressor gene. In 90 MBs, no mutations of the
      hSNF5/INI1 gene were identified. Thus, our study virtually rules out hSNF5/INI1
      as a tumour suppressor gene involved in the pathogenesis of medulloblastoma.

PMID- 11972801
TI  - Recurrent haemangioblastoma with glial differentiation.

PMID- 11972860
TI  - Suppression of experimental lupus nephritis by aberrant expression of the soluble
      E-selectin gene.
AB  - Circulating leukocytes, particularly neutrophils and monocytes, are important
      effector cells in the induction of many forms of glomerulonephritis. Adhesion
      molecules, especially selectins, are also thought to be critical for the
      development of this disease. We examined the possible suppressive effect of
      soluble E-selectin on the development of experimental lupus nephritis induced by
      the injection of a hybridoma clone (2B11.3) derived from an MRL/MpJ-lpr/lpr lupus
      mouse. This clone produces IgG3 antibodies that induce severe proliferative
      glomerulonephritis resembling lupus nephritis when injected into normal mice.
      Transgenic mice with a soluble E-selectin gene were injected intraperitoneally
      with the hybridoma cells and histopathologically examined on day 15. As a result,
      the development of glomerulonephritis was significantly suppressed. This
      suppression was characterized by fewer inflammatory cell infiltrates, compared
      with non-transgenic litter mates, despite the fact that there were no remarkable
      differences in immunoglobulin deposits or expression of E-selectin between the
      two groups. These findings suggest that by controlling inflammatory cell
      infiltration, soluble E-selectin plays a preventative role in the development of
      a particular type of lupus nephritis.

PMID- 11972861
TI  - Cycloheximide induces apoptosis of astrocytes.
AB  - Cultured rat astrocytes were incubated in the presence of cycloheximide (CHX; 20
      microg/mL), a potent neuroprotective agent. Then cells were subjected to DNA gel
      electrophoresis. Electrophoresis showed DNA ladder formation, which is
      characteristic of apoptosis. Inhibitors of interleukin-1beta-converting enzyme
      (ICE) and caspase 32(CPP32), which play critical roles in certain apoptotic
      pathways, did not block the cycloheximide-induced apoptosis of cultured
      astrocytes. This observation indicates that the role of ICE and CPP32 is not
      significant in the CHX-induced astrocyte apoptosis process. When the blood-brain
      barrier was disrupted in the rat, the number of brain cells undergoing apoptosis
      was significantly higher after cycloheximide administration, in contrast to
      controls. Of the cells that produced glial fibrillary acidic protein, some were
      observed to undergo apoptosis. Although CHX has been shown to be useful as a
      neuroprotective agent against ischemic neuronal death, astroglial toxicity may be
      problematic, depending on CHX concentration. Therefore, a prudent use of this
      compound is recommended.

PMID- 11972862
TI  - Predictive and prognostic markers for invasive breast cancer.
AB  - Breast cancer is one of the most serious carcinomas among women worldwide, yet
      there are now encouraging signs that improvements in the mortality rate may be
      possible. The use of hormone therapy and chemotherapy has been widely accepted as
      treatment for breast cancer. Predictive factors can be used to predict response
      or lack of response to a particular therapy, and prognostic factors can be useful
      in making decisions about which patients should receive adjuvant therapy.
      Histopathology remains the universal basis of diagnosis, with the identification
      of new surrogate markers for potential new treatments. These are aimed at
      blocking tumor cell proliferation, neutralizing growth factors, stimulating
      apoptosis and blocking metastasis, and represent an integral part of new
      approaches for improving clinical management of patients with breast cancer. We
      review the standard predictive and prognostic factors that are routinely
      available today, and also describe some of the new, potential markers that are
      currently under investigation.

PMID- 11972863
TI  - Ulcerative colitis-associated neoplasia.

PMID- 11972864
TI  - Antisense oligodeoxynucleotides against thrombomodulin suppress the cell growth
      of lung adenocarcinoma cell line A549.
AB  - Thrombomodulin (TM), an anticoagulant factor on endothelial cells, is known to be
      expressed in non-endothelial cells as well. In neoplastic cells of lung
      adenocarcinomas, TM is expressed but its correlation with growth potential has
      not been studied. As TM expression has a negative correlation with cell
      proliferation in lung squamous cell carcinomas, we examined its growth effect on
      lung adenocarcinoma cells of the A549 cell line by inhibiting TM expression with
      antisense oligodeoxynucleotides (ODN). In the antisense ODN transfected cells,
      the expression of TM mRNA was decreased to 49% at 12 h and 47% at 24 h, which was
      in accordance with TM expression at the protein level. By IdU (5-iodo-2'
      deoxyuridine) incorporation assay, the growth of A549 cells was found to have
      decreased to 36% of the control level at 24 h post-transfection. The suppression
      of cell growth was maintained in a concentration-dependent manner for 48 h after
      transfection, when the expression of TM started to rebound. In the transfected
      cells, the G1 phase cell count was reduced to 60.7%, compared with 68.2% in the
      control transfectants. These results suggest that TM expression may play a
      suppressive role in the proliferation activity of A549 lung adenocarcinoma cells.

PMID- 11972866
TI  - Differential distribution of basement membrane type IV collagen alpha1(IV),
      alpha2(IV), alpha5(IV) and alpha6(IV) chains in colorectal epithelial tumors.
AB  - In this study, we examined the relationship between the histopathological grade
      and immunohistochemical localization of six genetically distinct type IV collagen
      alpha chains, the major component of basement membrane (BM), in normal and
      neoplastic colorectal tissues. In the normal colorectal mucosa, alpha1/alpha2(IV)
      and alpha5/alpha6(IV) chains were stained in all epithelial BM. However,
      alpha3/alpha4(IV) chains were restrictively immunostained in the BM of the apical
      surface epithelium. Similar immunostaining profiles for alpha1/alpha2(IV) and
      alpha5/alpha6(IV) chains were observed in tubular adenomas with mild/moderate
      atypia. However, in intramucosal carcinomas, both alpha1/alpha2(IV) chains were
      linearly stained in the BM of cancer cell nests, while the assembly of
      alpha5/alpha6(IV) chains into the BM was inhibited in a discontinuous or
      negatively stained pattern. The normal colorectal mucosa forms a second network
      of BM composed of alpha5/alpha6(IV), partly alpha3/alpha4(IV) chains, in addition
      to the classic network of alpha1/alpha2(IV) chains. The differential
      immunohistochemical localization of the type IV collagen alpha5/alpha6 chains
      could be one diagnostic marker for the invasiveness of colorectal cancer.

PMID- 11972865
TI  - Phenotypic changes and cell cycle activation in early tubulointerstitial injury
      of rat adriamycin nephrosis.
AB  - Tubular response, including phenotypic changes against a variety of injuries, is
      an initial event that promotes tubulointerstitial injuries. Using the progressive
      kidney disease model of rat adriamycin (ADR) nephrosis, the present study focused
      on the cell cycle activation and phenotypic changes that occur in the tubuli in
      early tubulointerstitial injury in ADR nephrosis. At 12 weeks, experimental
      animals developed overt nephrosis with tubulointerstitial injury, which
      correlated well with the degree of proteinuria and incidence of
      glomerulosclerosis. Initial pathology of the tubuli showed a slight dilatation of
      tubuli, which tended to occur in individual nephrons. Immunohistochemistry
      demonstrated that vimentin-positive tubuli and osteopontin (OPN)-positive tubuli
      were associated mostly with proliferating cell nuclear antigen expression.
      Protein levels of OPN in the renal cortex were correlated with the level of
      proteinuria by western blotting. Vimentin- and OPN-expressing tubuli were tightly
      associated with a peritubular influx of alpha-smooth muscle actin (SMA)-positive
      cells or ED-1-positive cells. In addition, we found thrombomodulin+/ TUNEL+ (dUTP
      biotin nick-end labeling) peritubular endothelial cells and ED-1+/alpha-SMA+
      cells at an early stage among interstitial inflammatory cells. These results
      suggest that cell cycle activation in tubular cells forms the background for the
      phenotypic tubular changes that are involved in chronic tubulointerstitial injury
      in ADR nephrosis.

PMID- 11972867
TI  - Modified and simplified western blotting protocol: use of intermittent microwave
      irradiation (IMWI) and 5% skim milk to improve binding specificity.
AB  - A modified western blotting protocol was developed to increase the binding
      specificity of antigens and antibodies, using intermittent microwave irradiation
      (IMWI) with seven antibodies and two cell lines. The method was based on IMWI of
      the blotting membrane in the immunoblotting step using 5% skim milk as the
      diluting buffer. For some antibodies against p53, CDK4 and cyclinE, there were no
      distinct differences between the IMWI(+) and IMWI(-) counterparts; but
      improvement over the standard protocol was noted in both. For some antibodies,
      such as the polyclonal antibody against tubulin and the monoclonal antibodies
      against beta-tubulin, cyclinA and cyclinB1 (which were otherwise difficult to
      obtain good results with), IMWI was extremely effective, resulting in clear,
      specifically binding bands and a clean background. Moreover, the times were
      reduced from 8 to 3 h. Both the IMWI(+) and IMWI(-) protocols can be applied as
      simple, rapid and highly specific detection techniques for applications with
      various antigens, reducing background 'noise' to a minimum.

PMID- 11972868
TI  - Ductal adenoma of the breast with chondromyxoid change.
AB  - A case of ductal adenoma of the breast in a 66-year-old woman is reported. The
      lesion was a small, firm nodule present in the periareolar area of the left
      breast. It showed extensive hyalinization with tubular structures and spotty
      calcifications. In spite of such a regressive and relatively well-circumscript
      appearance, focal eccentric peripheral sclerosis with distorted ductal structures
      suggested malignancy. However, immunohistochemical examination demonstrated a
      preserved myoepithelial layer surrounding the ducts. The tumor also showed focal
      chondromyxoid change and adipocytic differentiation. The myxoid change started
      exclusively around the ductal structures within the hyalinized acellular stroma
      and coalesced to form larger chondromyxoid areas. Myoepithelial cells
      constituting the ductal elements may have been responsible for the aberrant
      mesenchymal differentiation of this tumor.

PMID- 11972869
TI  - Invasive ductal carcinoma associated with tubular adenoma of the breast.
AB  - We report an extremely rare case of the colocalization of a tubular adenoma and
      an invasive ductal carcinoma occurring in a 55-year-old woman. Following
      radiographical evaluation, fine-needle aspiration cytology of the left breast
      tumor was undertaken. Because cytological examination revealed malignancy, a
      partial mastectomy was performed. Histologically, the tumor (measuring 1.7 x 1.3
      cm) comprised two distinct parts: tubular adenoma and invasive ductal carcinoma.
      The invasive ductal carcinoma showed a solid pattern, high nuclear and structural
      atypia and frequent mitotic figures, while the tubular adenoma consisted of a
      proliferation of small ducts lined by single layers of epithelial and
      myoepithelial cells with bland nuclei and inconspicuous nucleoli. The
      histological boundary was clearly defined between the tubular adenoma and the
      invasive ductal carcinoma, and between the tubular adenoma and the surrounding
      breast tissue. The current case might be a collision between separate tubular
      adenoma and invasive ductal carcinoma, but the malignant transformation of a
      tubular adenoma cannot be ruled out. Both the long-term observation of this case
      and analysis of more cases may enable us to determine the histological
      characteristics and clinical significance of invasive ductal carcinoma associated
      with tubular adenoma.

PMID- 11972870
TI  - Squamous cell carcinoma arising from a seminal vesicular cyst: possible
      relationship between chronic inflammation and tumor development.
AB  - A case of squamous cell carcinoma arising within an acquired seminal vesicular
      cyst is described. A 61-year-old man was hospitalized because of hemospermia and
      dysuria. Under the diagnosis of a left seminal vesicular cyst, surgical resection
      was performed. Pathological examination revealed squamous cell carcinoma within a
      seminal vesicular cyst, along with squamous metaplastic foci and severe chronic
      inflammation. Cell proliferation, determined with reference to MIB-1 labeling
      indices, showed a stepwise increase from normal columnar epithelium, through
      squamous metaplasia, to squamous cell carcinoma. Sporadic p53 protein
      accumulation without evident gene mutations was also apparent in both the
      carcinoma and squamous metaplastic lesions. We therefore concluded that the
      squamous cell carcinoma might have developed from squamous metaplastic foci
      associated with chronic inflammatory stimulation, within a seminal vesicular
      cyst.

PMID- 11972873
TI  - The cell biology of MHC class I antigen presentation.
AB  - MHC class I antigen presentation refers to the co-ordinated activities of many
      intracellular pathways that promote the cell surface appearance of MHC class
      I/beta2m heterodimers loaded with a spectrum of self or foreign peptides. These
      MHC class I peptide complexes form ligands for CD8 positive T cells and NK cells.
      MHC class I heterodimers are loaded within the endoplasmic reticulum (ER) with
      peptides derived from intracellular proteins. Alternatively, MHC class I
      molecules may be loaded with peptides derived from extracellular proteins in a
      process called MHC class I cross presentation. This pathway is less well defined
      but can overlap those pathways operating in classical MHC class I presentation
      and has recently been reviewed elsewhere (1). This review will address the
      current concepts regarding the intracellular assembly of MHC class I molecules
      with their peptide cargo within the ER and their subsequent progress to the cell
      surface.

PMID- 11972874
TI  - Calreticulin binds to the alpha1 domain of MHC class I independently of tapasin.
AB  - Prior to binding to antigenic peptide, the major histocompatibility complex (MHC)
      heavy chain associates with an assembly complex of proteins that includes
      calreticulin, tapasin, and the transporter associated with antigen processing
      (TAP). Our data show that calreticulin can bind weakly to Ld without tapasin's
      assistance, and that deglycosylation of the alpha1 domain results in a primary
      loss of binding to calreticulin rather than tapasin. We have also shown that high
      amounts of wild-type tapasin are still unable to associate with MHC class I in
      the absence of the MHC class I/calreticulin interaction, confirming the central
      role of calreticulin in the formation of the MHC class I assembly complex.

PMID- 11972875
TI  - HLA class II haplotypes associated with pulmonary interstitial lesions of
      polymyositis/dermatomyositis in Japanese patients.
AB  - To elucidate the immunogenetic background of idiopathic inflammatory myopathies
      (IIM) such as polymyositis (PM), dermatomyositis (DM) and any overlapping
      subsets, with other collagen vascular diseases, HLA class I antigens and class II
      alleles were determined and compared from individuals with various clinical and
      serological features of IIM, including pulmonary interstitial lesions (PI).
      Seventy-three Japanese patients with myositis (32 PM, 18 DM, 23 overlapped
      subsets) and 62 healthy unrelated controls were enrolled onto the study.
      Statistical differences between groups were determined by the Fisher's exact
      probability test. Serum fluorescent antinuclear antibody, rheumatoid factor (RF),
      anti-SS-A/Ro antibody, anti-Jo1 antibody and anti-U1 RNP antibody were examined
      using routine methods. PI was detected by chest X-ray and/or computed tomography.
      In patients with DM, the frequency of the HLA-DRB1*1302-DQA1*0102-DQB1*0604
      haplotype was significantly higher than in the healthy controls (42.1% vs 17.7%),
      and in the patients with PM (42.1% vs 9.4%). Furthermore, the frequency of the
      HLA-DRB1*0405-DQA1*03-DQB1*0401 haplotype was higher in the PM patients with PI
      than in the controls (50.0% vs 17.7%), and PM without PI (50.0% vs 5.5%). These
      results suggest that in terms of HLA class II association, Japanese DM and PM,
      and PM with and without PI, belong to different clinical groups.

PMID- 11972876
TI  - Genetic predispositions for the presence of cryoglobulinemia and serum
      autoantibodies in Chinese patients with chronic hepatitis C.
AB  - Chronic hepatitis C virus (HCV) infection may induce immunological disorders in
      the host such as the presence of cryoglobulinemia or serum autoantibodies. The
      pathogenesis of these phenomena remains unclear but may reflect the host's
      genetic predispositions. The aim of this study was to evaluate the association
      between these immunological manifestations and human leukocyte antigen (HLA)
      expression in Chinese patients with chronic hepatitis C. The presence of serum
      cryoglobulin and autoantibodies (antinuclear antibody, antismooth muscle
      antibody, antimitochondrial antibody, antiliver-kidney-microsomal antibody) was
      determined in 122 Chinese patients with chronic hepatitis C. HLA class I and
      class II antigens were measured by microlymphocytotoxicity assay or by DNA typing
      in 122 chronic hepatitis C patients and 228 healthy controls. Of the 122 patients
      with chronic hepatitis C, 52 (43%) had cryoglobulinemia and 48 (39%) had serum
      autoantibodies. A significant difference in HLA frequency was noted for DR3,
      which was found in 36.5% of patients with cryoglobulinemia compared with 8.6% of
      patients without cryoglobulinemia and 11.3% of healthy controls. A significant
      difference in HLA frequency was also noted for DR4, which was found in 45.8% of
      patients with serum autoantibodies compared with 17.6% of patients without serum
      autoantibodies and 19% of healthy controls. Our results suggest the existence of
      HLA-linked susceptibility genes (DR3 or DR4) for the development of
      cryoglobulinemia or serum autoantibodies in Chinese patients with chronic
      hepatitis C.

PMID- 11972877
TI  - HLA profile of three ethnic groups living in the North-Western region of Russia.
AB  - HLA class II alleles were determined by PCR-SSO and PCR-SSP typing of DNA samples
      from 55 Nentsy, 81 Saami and 73 Pomor individuals from the North-European part of
      Russia. The results were compared with similar data from Russians. A high
      frequency of the DRB1*04-DQA1*0301-DQB1*0302 haplotype and a low frequency of the
      DRB1*11-DQA1*0501-DQB1*0301 haplotype, observed in all three ethnic groups, may
      indicate a common aboriginal component in their ancestry. Saami and Pomors
      displayed a similar pattern of allele and haplotype distribution, with the
      exception of the DRB1*04-DQA1*0304-DQB1*0301 haplotype, which was significantly
      higher among Saami compared Nentsy, Pomors and Russians. Nentsy individuals had a
      particularly high frequency of the DRB1*09-DQA1*0301-DQB1*0303 and the DRB1*12
      DQA1*0501-DQB1*0301 haplotypes. Genetic distances and correspondence analysis
      show that Pomors have a close relationship with Norwegians and Finns, whereas
      Nentsy and Saami are more closely related to Oriental populations.

PMID- 11972878
TI  - Specific amplification of the HLA-DRB4 gene from c-DNA. Complete coding sequence
      of the HLA alleles DRB4*0103101 and DRB4*01033.
AB  - We present the complete coding sequence of the HLA alleles DRB4*0103101 and
      DRB4*01033 derived from the lymphoblastoid cell line G081, established from an
      individual of Spanish Gypsy ethnic origin. This cell was typed by PCR-SSP and
      reverse SSO as DRB4*0103101 but further characterization of the DRB4 gene by
      sequence-based typing (SBT) demonstrated heterozygosity at codon 78 (TAC, TAT).
      With the aim of confirming this polymorphism, RNA isolated from G081 was
      subjected to RT-PCR using primers designed to recognize specifically the 5' and
      3' UT regions of HLA-DRB4 and the product was cloned and sequenced. Nucleotide
      sequences derived from seven clones confirmed the heterozygosity of G081, as they
      corresponded to two open reading frames of 801 nucleotides that matched either
      DRB4*0103101 or the recently described DRB4*01033, for which a partial sequence,
      spanning exons 2 and 3, has been reported. The phenotype of G081 (A*01; B*0702,
      *1302/1303; Cw*0602, *07; DRB1*0403, *0701; DRB4*0103101, *01033; DQB1*0202,
      *0302; DQA1*0201, *0301) is consistent with a proposed association of DRB4*01033
      with DRB1*0403 and DQB1*0302.

PMID- 11972879
TI  - Two new HLA class I alleles recognised by PCR sequence-specific primer and
      sequencing based typing: B*3805 and Cw*0408.
AB  - Two new HLA class I alleles have been recognised by molecular-based typing.
      B*3805 was initially identified by polymerase chain reaction using sequence
      specific primers (PCR-SSP) and afterwards confirmed by sequencing based typing
      (SBT) studies in a Spanish Caucasian blood cord unit. A unique nucleotide change
      throughout exons 2, 3 and 4, leading to the amino acid replacement Ser11Ala,
      differentiates B*3801 and *3805. This position behaves as a dimorphic residue in
      HLA-B and -C loci, and seems to be structurally unrelated to peptide and TcR
      recognition. Cw*0408 was first detected by SBT in two African American bone
      marrow donors in combination with its most structurally related allele, Cw*04011.
      The single amino acid change found between Cw*04011 and Cw*0408 was Thr163Leu, a
      residue involved in pocket A of the peptide-binding cleft. This new allele could
      be the result of a gene conversion event between Cw*04011 and any of the Cw*03
      alleles.

PMID- 11972880
TI  - Sequence of two new HLA-Cw alleles: HLA-Cw*0313 and HLA-Cw*1208.
AB  - Two new HLA-C alleles have been identified by reverse line blot assay and direct
      sequencing of polymerase chain reaction (PCR) products. The first polymorphism
      encodes an amino acid change from lysine in Cw*12022 to asparagine in Cw*1208 at
      residue 66. The second polymorphism encodes two amino acid changes from
      isoleucine in Cw*03031 to threonine in Cw*0313 at residue 93 and isoleucine to
      leucine at residue 94. The functional significance of these polymorphisms on
      peptide-binding and/or T-cell recognition is unknown.

PMID- 11972881
TI  - Identification of sequence errors in HLA-DRB1*0801 and HLA-DRB1*12011.
AB  - We report the identification of previously unrecognised errors in the nucleotide
      sequences of two long established HLA-DRB1 alleles, DRB1*0801 and DRB1*12011. The
      errors were detected during development of sequencing based typing (SBT) methods
      for the HLA-DRB1 locus and were confirmed by sequencing cell lines from the 10th
      International Histocompatibility Workshop (IHW).

PMID- 11972882
TI  - HLA-DQA1 and -DQB1 genes and Helicobacter pylori infection in Italian patients
      with gastric adenocarcinoma.
AB  - Both HLA-DQA1 and -DQB1 genes and Helicobacter pylori infection have been linked
      to gastric cancer. The aim of this work was to determine if HLA-DQA1 and -DQB1
      alleles are presented at altered frequency in Italian patients with gastric
      adenocarcinoma and H. pylori infection. Oligotyping for HLA-DQA1 and -DQB1 and H.
      pylori serology was performed for 50 patients with gastric adenocarcinoma and
      compared with 80 patients with colonic adenocarcinoma and 179 healthy subjects.
      H. pylori infection was present in 76% of gastric cancer patients, 77.5% of
      colonic cancer patients, and 72% of controls. The prevalence of infection was not
      significantly different in the three groups of subjects sorted according to their
      HLA-DQA1 or -DQB1 status. Apart from HLA-DQA1* 0201, which was less common in
      patients with colonic carcinoma than controls, no other HLA-DQA1 and no HLA-DQB1
      allele were present at altered frequency in patients with gastric or colonic
      cancer. Neither anatomical location and histological type of cancer nor the
      presence of lymph node or distant metastases were significantly associated with
      specific HLA-DQA1 or -DQB1 alleles or H. pylori infection. Both HLA-DQA1 and 
      DQB1 genes have a minor, if any, role in H. pylori infection and gastric
      carcinogenesis.

PMID- 11972883
TI  - Identification of a novel HLA-DPB1 allele, DPB1*02014, by sequence-based typing.
AB  - In this report we describe the identification of a novel DPB1 allele, DPB1*02014,
      found in an Italian Caucasian individual. The new allele was detected during
      routine HLA sequence-based typing (SBT) for an individual undergoing bone marrow
      transplantation. DPB1*02014 was identical to DPB1*02012 except for a single
      nucleotide substitution in codon 72 (GTG-->GTT). This nucleotide change
      represents a synonimous mutation, as both triplets code for a valine. This new
      allele has been submitted to GenBank and assigned the accession number AF326565.
      The WHO Nomenclature Committee has officially assigned the name DPB1*02014.

PMID- 11972884
TI  - Identification of a novel HLA-B*07 allele--HLA-B*0726.
AB  - We describe here, the identification of a novel HLA-B*07 allele named HLA-B*0726.
      This allele was found in a Caucasian individual serologically typed as HLA-B7,
      B35. Novel DNA probe patterns for the HLA-B*07 allele were found using HLA-B
      specific reverse sequence-specific oligonucleotide probe (SSOP) and sequence
      specific primer (SSP) typing. DNA sequencing demonstrated the presence of a new
      HLA-B*07 sequence variant encoding a single nucleotide substitution from a G to a
      T at nucleotide 539 in exon 3. This results in an amino acid substitution from
      arginine to leucine at residue 156 in exon 3.

PMID- 11972885
TI  - Description of fourteen new DRB alleles found in a stem cell donor registry.
AB  - Fourteen DRB alleles, DRB1*0705, DRB1*11014, DRB1*1134, DRB1*1136, DRB1*1141,
      DRB1*1335, DRB1*1337, DRB1*1338, DRB1*1342, DRB1*1343, DRB1*1349, DRB1*1510,
      DRB3*0105, and DRB5*0103, are described. Among them, eleven are variants which
      differ by only one nucleotide from previously described alleles, including one
      silent variant (DRB1*11014). Alleles, DRB1*0705, DRB1*1335 and DRB3*0105, display
      unique sequence motifs that have never been observed in DRB alleles.

PMID- 11972886
TI  - Complete cDNA sequences of the HLA-DRB1*14011, *1402, *1403 and *1404 alleles.
AB  - Sequencing studies of HLA class II molecules have been focused almost exclusively
      on the highly polymorphic exon 2. In this study the complete cDNA sequence of
      four alleles of the DR14 lineage (DR52 group) are reported for the first time.
      The HLA-DRB1*1402 and *1403 sequences were shown to be identical to the
      previously determined DRB1*13011 sequence, also of the DR52 group, in exons 1, 3,
      4, 5 and 6. HLA-DRB1*14011 and *1404 were identical to DRB1*13011 in exons 1, 4,
      5 and 6 sequences while they showed specific features within their exon 3
      sequence. Both alleles showed a synonymous substitution at the third base of
      codon 114. However, DRB1*14011 also has a non-synonymous substitution at the
      first base of codon 112 which results in a histidine to tyrosine substitution.
      This is a novel substitution as Histidine 112 is conserved in all known HLA class
      II B genes.

PMID- 11972887
TI  - The IL12B gene does not confer susceptibility to coeliac disease.
AB  - Coeliac disease (CD) is a chronic inflammatory disorder where dietary gluten is
      not tolerated. In the lesion there are gluten reactive T cells predominantly
      secreting gamma-interferon. Both HLA and non-HLA genes contribute to CD
      susceptibility. Interleukin-12 (IL-12) regulates gamma-interferon production. The
      IL12B gene is located in a region (5q31.1-33.1) where there is evidence for
      linkage with CD. Allele 1 of an IL12B 3'UTR single-nucleotide polymorphism leads
      to increased expression of IL-12, and was recently implicated in susceptibility
      for type 1 diabetes (T1D). We found no evidence for association of allele 1 to CD
      by the transmission/disequilibrium test or case-control approach. No increased
      frequency was observed in patients belonging to families where the disease was
      linked to markers on chromosome 5q. Unlike T1D, allele 1 does not appear to
      confer susceptibility to CD.

PMID- 11972888
TI  - Nomenclature for factors of the HLA system, update August 2001.

PMID- 11972889
TI  - Nomenclature for factors of the HLA system, update September 2001.

PMID- 11972890
TI  - Review cutaneous lesions of the canine scrotum.
AB  - Scrotal lesions are uncommon and often present a diagnostic challenge. In the
      veterinary literature there are no texts devoted to this subject. This study
      reviews and illustrates canine scrotal lesions following an aetiological layout
      with the aim of facilitating clinical identification and diagnosis. Infectious,
      immune-mediated, endocrinological and neoplastic conditions are the most commonly
      reported causes of scrotal lesions in the dog. They may affect the scrotum only
      or other parts of the body as well. The clinical presentation of the lesions, the
      presence of primary or secondary lesions and the presence of clinical signs of
      systemic disease may help in obtaining a diagnosis. In some cases further
      investigations are necessary to reach a definitive diagnosis. Histopathology aids
      in understanding pathological reactions of the scrotal skin but unfortunately
      this is not commonly carried out and few reports in the literature include
      histopathology. The list of conditions given in this review is not exhaustive and
      other, more rare, diseases may be encountered.

PMID- 11972891
TI  - Cyclosporine decreases skin lesions and pruritus in dogs with atopic dermatitis:
      a blinded randomized prednisolone-controlled trial.
AB  - During the last decade, oral cyclosporin (CsA) has proven to be effective, in
      randomized controlled trials, for the treatment of atopic dermatitis (AD) in
      human patients. The purpose of this blinded randomized controlled trial was to
      test the hypothesis that CsA was successful in reducing the gravity of clinical
      signs of AD in dogs. Thirty dogs with nonseasonal AD were randomly allocated to
      receive an oral solution of either NEORAL CsA (5 mg kg-1) or prednisolone (0.5 mg
      kg-1) once daily for 6 weeks. Before, and 3 and 6 weeks after therapy, skin
      lesions were graded by clinicians using the Canine AD Extent and Severity Index
      (CADESI). Pruritus was assessed by the owners using a visual analog scale (PVAS).
      In both groups, CADESI and PVAS values were significantly lower at 6 weeks post
      treatment than before the initiation of therapy (Friedman test, P < 0.0004). The
      percentage reductions in CADESI and PVAS values from baseline were not
      statistically different between groups (Mann-Whitney test, P > 0.3). In this
      experiment, the tolerability and safety of oral CsA and prednisolone appeared
      similar. One-fifth of dogs given oral CsA occasionally developed diarrhoea or
      soft stools. One dog that was given CsA developed a generalized papillomatous
      skin eruption during the second half of the trial. Our study provides randomized
      controlled trial evidence that CsA reduces the severity of clinical signs in dogs
      with nonseasonal AD. Moreover, the anti-allergic efficacy of CsA appears
      comparable with that of prednisolone. We propose that oral CsA should be
      considered as a valuable alternative to glucocorticoid therapy in dogs with AD.

PMID- 11972892
TI  - Canine atopic dermatitis: a retrospective study of 266 cases examined at the
      University of California, Davis, 1992-1998. Part I. Clinical features and allergy
      testing results.
AB  - The medical records of 266 dogs diagnosed as having atopic dermatitis were
      reviewed. Statistical data were evaluated referable to breed predilections,
      clinical signs and positive reactions to allergens. Positive reactions were most
      common to house dust mites (more common with clinical signs in the fall) followed
      by moulds (more common with clinical signs in the fall and spring). Dogs with
      positive reactions to moulds, trees or cultivated plants were more likely to have
      skin and ear yeast infections. Dogs with positive reactions to cultivated plants
      were more likely to have otitis externa and pedal lesions. Positive reactions to
      house dust were more common in dogs with early onset of signs and in those tested
      early in the disease. Dogs had more positive reactions to weeds when allergy
      tests were performed in the summer and fall. Positive reactions to flea antigen
      were highly correlated with the clinical diagnosis of flea allergy dermatitis.

PMID- 11972893
TI  - Canine atopic dermatitis: a retrospective study of 169 cases examined at the
      University of California, Davis, 1992-1998. Part II. Response to
      hyposensitization.
AB  - One hundred and sixty-nine dogs were diagnosed with atopic dermatitis, and
      treated with hyposensitization for at least 1 year based on the results of either
      intradermal skin tests (IDST) or enzyme-linked immunosorbant serum assays
      (ELISA). Excellent (i.e. hyposensitization alone controlled clinical signs), good
      (> 50% improvement), moderate (< 50% improvement) and no (clinical signs were
      unchanged) responses were seen in 19.5, 32.5, 20.1 and 27.8%, respectively. Age
      of onset, age when treatment was initiated or the duration of clinical signs had
      no influence on response to hyposensitization. Dogs having concurrent flea
      allergy dermatitis were statistically more likely to respond better than dogs
      with concurrent food allergies. Although not statistically significant, there
      were trends for Golden Retriever and male dogs to respond better than other
      breeds and female dogs, respectively. Dogs having more than 21 positive reactions
      in allergy tests and treated with more than 21 allergens had lower response
      scores, and a longer time course before achieving beneficial response. Lower
      response scores were seen in dogs having positive reactions to cultivated plants,
      grasses, trees or insects. There was no difference in response to
      hyposensitization whether based on IDST or ELISA results.

PMID- 11972894
TI  - Immunohistochemical localization of androgen and oestrogen receptors in canine
      hair follicles.
AB  - Skin biopsies from seven different body sites were obtained from 21 dogs of
      different breeds (short, normal, long hair), which were presented for euthanasia.
      Commercially available polyclonal antibodies were used for the
      immunohistochemical detection of androgen and oestrogen receptors. Both receptors
      showed a similar distribution in canine skin, with specific intranuclear
      staining. In the epidermis, the percentage of androgen receptor (AR)-positive
      cells, but not that of oestrogen receptor (ER)-positive cells, was significantly
      higher in samples from the thorax and the flank. In the dermal papilla, the
      percentage of ER-positive (but not AR-positive) cells was significantly lower in
      biopsies from the flank. No significant difference was found for both receptors
      between the locations in the outer root sheath, among the three different hair
      types, between sex and between intact and castrated dogs.

PMID- 11972895
TI  - Notoedric mange in two free-ranging North American racoons (Procyon lotor) in
      Japan.
AB  - Mange was diagnosed in two North American racoons (Procyon lotor) at Kamakura
      City in Kanagawa Prefecture, Japan. The mites were identified morphologically as
      Notoedres cati. Mite infestation affected the skin over the extremities and tail,
      and was characterized by moderate alopecia and erythematous dermatosis.
      Histopathologically, the affected skin showed marked epidermal hyperplasia and
      mites located within the parakeratotic stratum corneum. A slight dermal
      inflammatory response consisting principally of mononuclear cells was observed.
      N. cati mites were demonstrated in their tunnels using scanning electron
      microscopy (SEM). This is the first report of notoedric mange in racoons.

PMID- 11972896
TI  - CoreGenes: a computational tool for identifying and cataloging "core" genes in a
      set of small genomes.
AB  - BACKGROUND: Improvements in DNA sequencing technology and methodology have led to
      the rapid expansion of databases comprising DNA sequence, gene and genome data.
      Lower operational costs and heightened interest resulting from initial intriguing
      novel discoveries from genomics are also contributing to the accumulation of
      these data sets. A major challenge is to analyze and to mine data from these
      databases, especially whole genomes. There is a need for computational tools that
      look globally at genomes for data mining. RESULTS: CoreGenes is a global JAVA
      based interactive data mining tool that identifies and catalogs a "core" set of
      genes from two to five small whole genomes simultaneously. CoreGenes performs
      hierarchical and iterative BLASTP analyses using one genome as a reference and
      another as a query. Subsequent query genomes are compared against each newly
      generated "consensus." These iterations lead to a matrix comprising related genes
      from this set of genomes, e. g., viruses, mitochondria and chloroplasts.
      Currently the software is limited to small genomes on the order of 330 kilobases
      or less. CONCLUSION: A computational tool CoreGenes has been developed to analyze
      small whole genomes globally. BLAST score-related and putatively essential "core"
      gene data are displayed as a table with links to GenBank for further data on the
      genes of interest. This web resource is available at
      http://pumpkins.ib3.gmu.edu:8080/CoreGenes or http://www.bif.atcc.org/CoreGenes.

PMID- 11972897
TI  - Mesenchymally-derived insulin-like growth factor 1 provides a paracrine stimulus
      for trophoblast migration.
AB  - BACKGROUND: Trophoblast migration into maternal decidua is essential for normal
      pregnancy. It occurs in a defined time window, is spatially highly restricted,
      and is aberrant in some pathological pregnancies, but the control mechanisms are
      as yet ill-defined. At the periphery of the placenta, chorionic villi make
      contact with decidua to form specialised anchoring sites that feed interstitially
      migrating cytotrophoblast into the placental bed. RESULTS: Explants of first
      trimester mesenchymal villi on collagen type I developed cytotrophoblast
      outgrowths from the villous tips. However, in medium changed daily, cells did not
      progress to a migratory phenotype, remaining instead as a contiguous multi
      layered sheet. This suggested the need for another migration stimulus. To test
      the possibility that this might arise from mesenchymal cells, serum-free
      conditioned medium from first trimester placental fibroblasts was added to
      explant cultures. Cytotrophoblasts were stimulated to migrate in streams across
      the gel. Affinity depletion of Insulin-like growth factor from fibroblast medium
      reduced streaming activity, while the addition of exogenous IGF-I (10 ng/ml) to
      serum-free medium produced a streaming phenotype. IGF receptor type 1 (IGFR1) was
      present on cells in the columns, and streaming could be inhibited by antibody to
      this receptor. IGF-II and activin, known stimulators of cytotrophoblast
      migration, were also active in this model. CONCLUSIONS: These data suggest a
      paracrine interaction between villous mesenchyme and the cytotrophoblast in
      anchoring sites that stimulates trophoblast infiltration of decidua. Such a
      signal would be self-limiting since it diminishes with distance from the
      placenta. This is a novel mechanism in placental development.

PMID- 11972899
TI  - Interconversion of Anthozoa GFP-like fluorescent and non-fluorescent proteins by
      mutagenesis.
AB  - BACKGROUND: Within the family of green fluorescent protein (GFP) homologs, one
      can mark two main groups, specifically, fluorescent proteins (FPs) and non
      fluorescent or chromoproteins (CPs). Structural background of differences between
      FPs and CPs are poorly understood to date. RESULTS: Here, we applied site
      directed and random mutagenesis in order to to transform CP into FP and vice
      versa. A purple chromoprotein asCP (asFP595) from Anemonia sulcata and a red
      fluorescent protein DsRed from Discosoma sp. were selected as representatives of
      CPs and FPs, respectively. For asCP, some substitutions at positions 148 and 165
      (numbering in accordance to GFP) were found to dramatically increase quantum
      yield of red fluorescence. For DsRed, substitutions at positions 148, 165, 167,
      and 203 significantly decreased fluorescence intensity, so that the spectral
      characteristics of these mutants became more close to those of CPs. Finally, a
      practically non-fluorescent mutant DsRed-NF was generated. This mutant carried
      four amino acid substitutions, specifically, S148C, I165N, K167M, and S203A.
      DsRed-NF possessed a high extinction coefficient and an extremely low quantum
      yield (< 0.001). These spectral characteristics allow one to regard DsRed-NF as a
      true chromoprotein. CONCLUSIONS: We located a novel point in asCP sequence
      (position 165) mutations at which can result in red fluorescence appearance.
      Probably, this finding could be applied onto other CPs to generate red and far
      red fluorescent mutants. A possibility to transform an FP into CP was
      demonstrated. Key role of residues adjacent to chromophore's phenolic ring in
      fluorescent/non-fluorescent states determination was revealed.

PMID- 11972898
TI  - Four signature motifs define the first class of structurally related large coiled
      coil proteins in plants.
AB  - BACKGROUND: Animal and yeast proteins containing long coiled-coil domains are
      involved in attaching other proteins to the large, solid-state components of the
      cell. One subgroup of long coiled-coil proteins are the nuclear lamins, which are
      involved in attaching chromatin to the nuclear envelope and have recently been
      implicated in inherited human diseases. In contrast to other eukaryotes, long
      coiled-coil proteins have been barely investigated in plants. RESULTS: We have
      searched the completed Arabidopsis genome and have identified a family of
      structurally related long coiled-coil proteins. Filament-like plant proteins
      (FPP) were identified by sequence similarity to a tomato cDNA that encodes a
      coiled-coil protein which interacts with the nuclear envelope-associated protein,
      MAF1. The FPP family is defined by four novel unique sequence motifs and by two
      clusters of long coiled-coil domains separated by a non-coiled-coil linker. All
      family members are expressed in a variety of Arabidopsis tissues. A homolog
      sharing the structural features was identified in the monocot rice, indicating
      conservation among angiosperms. CONCLUSION: Except for myosins, this is the first
      characterization of a family of long coiled-coil proteins in plants. The tomato
      homolog of the FPP family binds in a yeast two-hybrid assay to a nuclear envelope
      associated protein. This might suggest that FPP family members function in
      nuclear envelope biology. Because the full Arabidopsis genome does not appear to
      contain genes for lamins, it is of interest to investigate other long coiled-coil
      proteins, which might functionally replace lamins in the plant kingdom.

PMID- 11972901
TI  - Food Allergy Testing: Problems in Identification of Allergenic Foods.
AB  - The greatest challenge in managing food allergy or intolerance is identifying the
      food that is responsible for the symptoms. The medical model of a diagnosis based
      on tests appropriate to the symptoms, which dictates the usual most effective
      treatment strategy, does not work well in the management of adverse reactions to
      foods. A single test could not identify the specific trigger for the wide array
      of symptoms that can result from food sensitivity, because the immunological,
      physiological and biochemical reactions that mediate food sensitivity are so
      diverse. Skin tests, blood tests for food antigen-specific antibodies, and other
      in vitro tests cannot provide the same information as well-controlled elimination
      and challenge. Once the reactive foods have been identified, management of the
      condition may be effectively achieved by a diet that avoids the culprit food
      components and supplies complete balanced nutrition from alternative sources. A
      suitably qualified dietitian/ nutritionist is the most appropriate health care
      practitioner to inform and supervise food-sensitive people in identifying and
      avoiding the specific food components that are responsible for their symptoms,
      and in obtaining complete nutrition from an appropriately selected diet.

PMID- 11972902
TI  - The Chronic Dieting Syndrome: Metabolic and Behavioural Characteristics.
AB  - The chronic dieting syndrome has been described as a situation in which a person
      is overly focused on dieting, but has nonpathological psychological function. At
      any given time, an estimated 50% of North American women are participating in
      some type of dieting behaviour. In this study, energy metabolism and lifestyle
      behaviours were investigated in 172 women who met the criteria for the chronic
      dieting syndrome. The following measurements describe the study participants
      (mean SD): height, 163.2 6.0 cm; weight, 80.3 16.3 kg; age, 39.4 7.0 years;
      resting energy expenditure (REE), 1352 196 kcal/day (92% of predicted).
      Frequently reported behaviours and attitudes included regular physical activity
      (73%) and dissatisfaction with body size and shape (78%). Those who started
      dieting at an early age (= 16 years, n = 90), which implies greater chronicity,
      were compared with those who started dieting later (> 16 years, n = 82) (p <
      0.001). The two groups' metabolic and behavioural characteristics did not differ.
      Over 21 years, restrictive eating behaviours had become the norm for these women,
      in spite of limited success at weight loss. The REE appeared to be reduced in
      only a small subset.

PMID- 11972900
TI  - Selective permeation and organic extraction of recombinant green fluorescent
      protein (gfpuv) from Escherichia coli.
AB  - BACKGROUND: Transformed cells of Escherichia coli DH5-alpha with pGFPuv, induced
      by IPTG (isopropyl-beta-d-thiogalactopyranoside), express the green fluorescent
      protein (gfpuv) during growth phases. E. coli subjected to the combination of
      selective permeation by freezing/thawing/sonication cycles followed by the three
      phase partitioning extraction (TPP) method were compared to the direct
      application of TPP to the same culture of E. coli on releasing gfpuv from the
      over-expressing cells. MATERIAL AND METHODS: Cultures (37 degrees C/100 rpm/ 24
      h; mu = 0.99 h(-1)-1.10 h(-1)) of transformed (pGFP) Escherichia coli DH5-alpha,
      expressing the green fluorescent protein (gfpuv, absorbance at 394 nm and
      emission at 509 nm) were sonicated in successive intervals of sonication (25
      vibrations/pulse) to determine the maximum amount of gfpuv released from the
      cells. For selective permeation, the transformed previously frozen (-75 degrees
      C) cells were subjected to three freeze/thaw (-20 degrees C/ 0.83 degrees C/min)
      cycles interlaid by sonication (3 pulses/6 seconds/25 vibrations). The
      intracellular permeate with gfpuv in extraction buffer (TE) solution (25 mM Tris
      HCl, pH 8.0, 1 mM beta-mercaptoethanol beta-ME, 0.1 mM PMSF) was subjected to the
      three-phase partitioning (TPP) method with t-butanol and 1.6 M ammonium sulfate.
      Sonication efficiency was verified on the application to the cells previously
      treated by the TPP method. The intra-cell releases were mixed and eluted through
      methyl HIC column with a buffer solution (10 mM Tris-HCl, 10 mM EDTA, pH 8.0).
      RESULTS: The sonication maximum released amount obtained from the cells was
      327.67 microg gfpuv/mL (20.73 microg gfpuv/mg total proteins-BSA), after 9 min of
      treatment. Through the selective permeation by three repeated
      freezing/thawing/sonication cycles applied to the cells, a close content of
      241.19 microg gfpuv/mL (29.74 microg gfpuv/mg BSA) was obtained. The specific
      mass range of gfpuv released from the same cultures, by the three-phase
      partitioning (TPP) method, in relation to total proteins, was higher, between
      107.28 microg/mg and 135.10 microg/mg. CONCLUSIONS: The selective permeation of
      gfpuv by freezing/thawing/sonication followed by TPP separation method was
      equivalent to the amount of gfpuv extracted from the cells directly by TPP;
      although selective permeation extracts showed better elution through the HIC
      column.

PMID- 11972903
TI  - A population study of integrate-and-fire-or-burst neurons.
AB  - Any realistic model of the neuronal pathway from the retina to the visual cortex
      (V1) must account for the bursting behavior of neurons in the lateral geniculate
      nucleus (LGN). A robust but minimal model, the integrate-and-fire-or-burst (IFB)
      model, has recently been proposed for individual LGN neurons. Based on this, we
      derive a dynamic population model and study a population of such LGN cells. This
      population model, the first simulation of its kind evolving in a two-dimensional
      phase space, is used to study the behavior of bursting populations in response to
      diverse stimulus conditions.

PMID- 11972904
TI  - Stable propagation of activity pulses in populations of spiking neurons.
AB  - We investigate the propagation of pulses of spike activity in a neuronal network
      with feedforward couplings. The neurons are of the spike-response type with a
      firing probability that depends linearly on the membrane potential. After firing,
      neurons enter a phase of refractoriness. Spike packets are described in terms of
      the moments of the firing-time distribution so as to allow for an analytical
      treatment of the evolution of the spike packet as it propagates from one layer to
      the next. Analytical results and simulations show that depending on the synaptic
      coupling strength, a stable propagation of the packet with constant waveform is
      possible. Crucial for this observation is neither the existence of a firing
      threshold nor a sigmoidal gain function--both are absent in our model--but the
      refractory behavior of the neurons.

PMID- 11972905
TI  - Population coding and decoding in a neural field: a computational study.
AB  - This study uses a neural field model to investigate computational aspects of
      population coding and decoding when the stimulus is a single variable. A general
      prototype model for the encoding process is proposed, in which neural responses
      are correlated, with strength specified by a gaussian function of their
      difference in preferred stimuli. Based on the model, we study the effect of
      correlation on the Fisher information, compare the performances of three decoding
      methods that differ in the amount of encoding information being used, and
      investigate the implementation of the three methods by using a recurrent network.
      This study not only rediscovers main results in existing literatures in a unified
      way, but also reveals important new features, especially when the neural
      correlation is strong. As the neural correlation of firing becomes larger, the
      Fisher information decreases drastically. We confirm that as the width of
      correlation increases, the Fisher information saturates and no longer increases
      in proportion to the number of neurons. However, we prove that as the width
      increases further--wider than (sqrt)2 times the effective width of the turning
      function--the Fisher information increases again, and it increases without limit
      in proportion to the number of neurons. Furthermore, we clarify the asymptotic
      efficiency of the maximum likelihood inference (MLI) type of decoding methods for
      correlated neural signals. It shows that when the correlation covers a nonlocal
      range of population (excepting the uniform correlation and when the noise is
      extremely small), the MLI type of method, whose decoding error satisfies the
      Cauchy-type distribution, is not asymptotically efficient. This implies that the
      variance is no longer adequate to measure decoding accuracy.

PMID- 11972906
TI  - The influence of limit cycle topology on the phase resetting curve.
AB  - Understanding the phenomenology of phase resetting is an essential step toward
      developing a formalism for the analysis of circuits composed of bursting neurons
      that receive multiple, and sometimes overlapping, inputs. If we are to use phase
      resetting methods to analyze these circuits, we can either generate phase
      resetting curves (PRCs) for all possible inputs and combinations of inputs, or we
      can develop an understanding of how to construct PRCs for arbitrary perturbations
      of a given neuron. The latter strategy is the goal of this study. We present a
      geometrical derivation of phase resetting of neural limit cycle oscillators in
      response to short current pulses. A geometrical phase is defined as the distance
      traveled along the limit cycle in the appropriate phase space. The perturbations
      in current are treated as displacements in the direction corresponding to
      membrane voltage. We show that for type I oscillators, the direction of a
      perturbation in current is nearly tangent to the limit cycle; hence, the
      projection of the displacement in voltage onto the limit cycle is sufficient to
      give the geometrical phase resetting. In order to obtain the phase resetting in
      terms of elapsed time or temporal phase, a mapping between geometrical and
      temporal phase is obtained empirically and used to make the conversion. This
      mapping is shown to be an invariant of the dynamics. Perturbations in current
      applied to type II oscillators produce significant normal displacements from the
      limit cycle, so the difference in angular velocity at displaced points compared
      to the angular velocity on the limit cycle must be taken into account. Empirical
      attempts to correct for differences in angular velocity (amplitude versus phase
      effects in terms of a circular coordinate system) during relaxation back to the
      limit cycle achieved some success in the construction of phase-resetting curves
      for type II model oscillators. The ultimate goal of this work is the extension of
      these techniques to biological circuits comprising type II neural oscillators,
      which appear frequently in identified central pattern-generating circuits.

PMID- 11972907
TI  - Fields as limit functions of stochastic discrimination and their adaptability.
AB  - For a particular type of elementary function, stochastic discrimination is shown
      to have an analytic limit function. Classifications can be performed directly by
      this limit function instead of by a sampling procedure. The limit function has an
      interpretation in terms of fields that originate from the training examples of a
      classification problem. Fields depend on the global configuration of the training
      points. The classification of a point in input space is known when the
      contributions of all fields are summed. Two modifications of the limit function
      are proposed. First, for nonlinear problems like high-dimensional parity
      problems, fields can be quantized. This leads to classification functions with
      perfect generalization for high-dimensional parity problems. Second, fields can
      be provided with adaptable amplitudes. The classification corresponding to a
      limit function is taken as an initialization; subsequently, amplitudes are
      adapted until an error function for the test set reaches minimal value. It is
      illustrated that this increases the performance of stochastic discrimination. Due
      to the nature of the fields, generalization improves even if the amplitude of
      every training example is adaptable.

PMID- 11972908
TI  - Learning to recognize three-dimensional objects.
AB  - A learning account for the problem of object recognition is developed within the
      probably approximately correct (PAC) model of learnability. The key assumption
      underlying this work is that objects can be recognized (or discriminated) using
      simple representations in terms of syntactically simple relations over the raw
      image. Although the potential number of these simple relations could be huge,
      only a few of them are actually present in each observed image, and a fairly
      small number of those observed are relevant to discriminating an object. We show
      that these properties can be exploited to yield an efficient learning approach in
      terms of sample and computational complexity within the PAC model. No assumptions
      are needed on the distribution of the observed objects, and the learning
      performance is quantified relative to its experience. Most important, the success
      of learning an object representation is naturally tied to the ability to
      represent it as a function of some intermediate representations extracted from
      the image. We evaluate this approach in a large-scale experimental study in which
      the SNoW learning architecture is used to learn representations for the 100
      objects in the Columbia Object Image Library. Experimental results exhibit good
      generalization and robustness properties of the SNoW-based method relative to
      other approaches. SNoW's recognition rate degrades more gracefully when the
      training data contains fewer views, and it shows similar behavior in some
      preliminary experiments with partially occluded objects.

PMID- 11972909
TI  - A parallel mixture of SVMs for very large scale problems.
AB  - Support vector machines (SVMs) are the state-of-the-art models for many
      classification problems, but they suffer from the complexity of their training
      algorithm, which is at least quadratic with respect to the number of examples.
      Hence, it is hopeless to try to solve real-life problems having more than a few
      hundred thousand examples with SVMs. This article proposes a new mixture of SVMs
      that can be easily implemented in parallel and where each SVM is trained on a
      small subset of the whole data set. Experiments on a large benchmark data set
      (Forest) yielded significant time improvement (time complexity appears
      empirically to locally grow linearly with the number of examples). In addition,
      and surprisingly, a significant improvement in generalization was observed.

PMID- 11972910
TI  - Bayesian framework for least-squares support vector machine classifiers, gaussian
      processes, and kernel Fisher discriminant analysis.
AB  - The Bayesian evidence framework has been successfully applied to the design of
      multilayer perceptrons (MLPs) in the work of MacKay. Nevertheless, the training
      of MLPs suffers from drawbacks like the nonconvex optimization problem and the
      choice of the number of hidden units. In support vector machines (SVMs) for
      classification, as introduced by Vapnik, a nonlinear decision boundary is
      obtained by mapping the input vector first in a nonlinear way to a high
      dimensional kernel-induced feature space in which a linear large margin
      classifier is constructed. Practical expressions are formulated in the dual space
      in terms of the related kernel function, and the solution follows from a (convex)
      quadratic programming (QP) problem. In least-squares SVMs (LS-SVMs), the SVM
      problem formulation is modified by introducing a least-squares cost function and
      equality instead of inequality constraints, and the solution follows from a
      linear system in the dual space. Implicitly, the least-squares formulation
      corresponds to a regression formulation and is also related to kernel Fisher
      discriminant analysis. The least-squares regression formulation has advantages
      for deriving analytic expressions in a Bayesian evidence framework, in contrast
      to the classification formulations used, for example, in gaussian processes
      (GPs). The LS-SVM formulation has clear primal-dual interpretations, and without
      the bias term, one explicitly constructs a model that yields the same expressions
      as have been obtained with GPs for regression. In this article, the Bayesian
      evidence framework is combined with the LS-SVM classifier formulation. Starting
      from the feature space formulation, analytic expressions are obtained in the dual
      space on the different levels of Bayesian inference, while posterior class
      probabilities are obtained by marginalizing over the model parameters. Empirical
      results obtained on 10 public domain data sets show that the LS-SVM classifier
      designed within the Bayesian evidence framework consistently yields good
      generalization performances.

PMID- 11972911
TI  - Neural network pruning with Tukey-Kramer multiple comparison procedure.
AB  - Reducing a neural network's complexity improves the ability of the network to
      generalize future examples. Like an overfitted regression function, neural
      networks may miss their target because of the excessive degrees of freedom stored
      up in unnecessary parameters. Over the past decade, the subject of pruning
      networks produced nonstatistical algorithms like Skeletonization, Optimal Brain
      Damage, and Optimal Brain Surgeon as methods to remove connections with the least
      salience. The method proposed here uses the bootstrap algorithm to estimate the
      distribution of the model parameter saliences. Statistical multiple comparison
      procedures are then used to make pruning decisions. We show this method compares
      well with Optimal Brain Surgeon in terms of ability to prune and the resulting
      network performance.

PMID- 11972912
TI  - Products of gaussians and probabilistic minor component analysis.
AB  - Recently, Hinton introduced the products of experts architecture for density
      estimation, where individual expert probabilities are multiplied and
      renormalized. We consider products of gaussian "pancakes" equally elongated in
      all directions except one and prove that the maximum likelihood solution for the
      model gives rise to a minor component analysis solution. We also discuss the
      covariance structure of sums and products of gaussian pancakes or one-factor
      probabilistic principal component analysis models.

PMID- 11972913
TI  - Optimization of the kernel functions in a probabilistic neural network analyzing
      the local pattern distribution.
AB  - This article proposes a procedure for the automatic determination of the elements
      of the covariance matrix of the gaussian kernel function of probabilistic neural
      networks. Two matrices, a rotation matrix and a matrix of variances, can be
      calculated by analyzing the local environment of each training pattern. The
      combination of them will form the covariance matrix of each training pattern.
      This automation has two advantages: First, it will free the neural network
      designer from indicating the complete covariance matrix, and second, it will
      result in a network with better generalization ability than the original model. A
      variation of the famous two-spiral problem and real-world examples from the UCI
      Machine Learning Repository will show a classification rate not only better than
      the original probabilistic neural network but also that this model can outperform
      other well-known classification techniques.

PMID- 11972914
TI  - Methods for binary multidimensional scaling.
AB  - Multidimensional scaling (MDS) is the process of transforming a set of points in
      a high-dimensional space to a lower-dimensional one while preserving the relative
      distances between pairs of points. Although effective methods have been developed
      for solving a variety of MDS problems, they mainly depend on the vectors in the
      lower-dimensional space having real-valued components. For some applications, the
      training of neural networks in particular, it is preferable or necessary to
      obtain vectors in a discrete, binary space. Unfortunately, MDS into a low
      dimensional discrete space appears to be a significantly harder problem than MDS
      into a continuous space. This article introduces and analyzes several methods for
      performing approximately optimized binary MDS.

PMID- 11972933
TI  - Factors associated with adherence to antiretroviral medication in HIV-infected
      patients.
AB  - The aim of the study was to assess adherence with antiretroviral medication in a
      sample of HIV patients in Hong Kong and identify predictors of adherence. The
      study used a cross-sectional correlational design. Adherence behaviour was
      assessed with the use of self-reports. Other scales assessed knowledge with HIV
      medication, coping, health locus of control, anxiety, depression and fatigue. A
      blood sample was also obtained to assess CD4+ counts and viral load.
      Sociodemographic characteristics and medical information were obtained from the
      medical records. A high adherence rate was found in this sample of 136
      predominantly Chinese patients. There were only 13.7% of the patients being
      classified as non-adherent. Predictors of adherence included high self-efficacy
      in terms of being certain that the medication schedule will be followed all or
      most of the time as directed, low tension-anxiety scores, and low intensity of
      nausea and vomiting (R2=0.304). An expanded regression model revealed additional
      factors influencing adherence, including coping variables, pain and numbness in
      the hands and feet, age, disease stage, internal locus of control, fatigue,
      family support and taking medication twice daily. This model explained 49% of the
      variance in adherence. The results suggest that adherence is a multidimensional
      concept. Every effort should be made to assess in individuals those variables
      found to affect adherence and alter them whenever possible. Continuous support of
      patients and individualized medication programmes that will help patients adjust
      their treatment to their lifestyle are recommended.

PMID- 11972932
TI  - A systematic review of strategies for partner notification for sexually
      transmitted diseases, including HIV/AIDS.
AB  - This review compares the effects of various sexually transmitted disease (STD)
      partner-notification strategies. Using review methods endorsed by the Cochrane
      Collaboration, it updates previous reviews, and addresses some of their
      methodological limitations. It includes 11 randomized controlled trials (RCTs)
      comparing two or more strategies, including 8014 participants. Only two trials
      were conducted in developing countries, and only two trials were conducted among
      HIV-positive patients. The review found moderately strong evidence that: (1)
      provider referral alone, or the choice between patient and provider referral,
      when compared with patient referral among patients with HIV or any STD, increases
      the rate of partners presenting for medical evaluation; (2) contract referral,
      when compared with patient referral among patients with gonorrhoea, results in
      more partners presenting for medical evaluation; (3) verbal, nurse-given health
      education together with patient-centred counselling by lay workers, when compared
      with standard care among patients with any STD, results in small increases in the
      rate of partners treated. The review concludes that there is a need for
      evaluations of interventions combining provider training and patient education,
      for evaluations conducted in developing countries, and for the measurement of
      potential harmful effects.

PMID- 11972934
TI  - HIV risk factors among patients with tuberculosis--Botswana 1999.
AB  - To identify factors associated with HIV in Botswana, a standardized questionnaire
      was administered to 135 tuberculosis patients with known HIV status. HIV-positive
      patients were more likely than HIV-negative patients to: be female (45% vs 26%
      (adjusted prevalence odds ratio (aPOR)=3.8, 95% confidence interval (CI)=1.1
      12.7)); be 26-35 years old (50% vs 19% (aPOR=2.7, CI=0.7-10.7)); be unmarried
      (91% vs 71% (aPOR=13.3, CI=2.5-72.7)); have higher income (24% vs 10% (aPOR=8.2,
      CI=1.6-42.9)); report separation from spouse/partner for work (63% vs 52%
      (aPOR=1.8, CI=0.5-6.2)); have 2 sex partners other than their regular partner
      (82% vs 67% (aPOR=1.8, CI=0.5-7.5)); and state that they or their partner drank
      alcohol before sex (77% vs 55% (aPOR=6.8, CI=1.9-24.1)). Only 22% of respondents
      used condoms during all of their past 10 sexual encounters. These data provide
      information for HIV prevention strategies.

PMID- 11972935
TI  - Microscopy of stained smears of vaginal secretion in the diagnosis of recurrent
      vulvovaginal candidosis.
AB  - This study was undertaken to determine the value of stained smears from the
      vaginal introitus and the posterior vaginal fornix for detection of candida
      morphotypes in the diagnosis of recurrent vulvovaginal candidosis (RVVC) in cases
      with an assumed novel attack of the condition, and to compare the value of
      microscopy of such smears in relation to candida culture, vaginal pH
      determinations and leucocyte esterase tests (LE). One hundred and thirteen women
      with a history and a current assumed attack of RVVC were studied by means of
      culture of samples from the vaginal introitus and posterior vaginal fornix on
      Sabouraud and CHROMagar. Microscopy of methylene blue- and Gram-stained smears
      from these sites was performed. The pH of vaginal secretion and the LE activity
      in vaginal flushing fluid was measured. Candida morphotypes were found
      significantly more often in the smears from candida culture-positive than culture
      negative women. There was no difference in this respect between the findings in
      the methylene blue- and Gram-stained smears. Differences were found in candida
      morphotypes among Candida albicans and non-albicans-positive cases, as
      blastoconidia were detected only in the latter cases. The leukocyte esterase
      activity score was higher in the candida-positive than in candida-negative cases.
      The study showed that microscopy of fixed, stained genital smears can play a role
      in attempts to distinguish cases infected and not infected by candida among
      patients consulting with an assumed novel attack of RVVC. Study of methylene blue
      stained smears is recommended as they represent an easier means than Gram-stained
      smears to diagnose genital candida infections in assumed RVVC cases.

PMID- 11972936
TI  - Observations on the microbiology of urethritis in black South African men.
AB  - The occurrence of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma
      genitalium was determined by molecular techniques in urine specimens from 182
      black South African men who had symptoms and/or overt signs of urethritis. Eighty
      six (47.3%) of these men were infected with N. gonorrhoeae. There were 185 men
      without overt evidence of urethritis, 16 (8.6%) of whom were also infected with
      N. gonorrhoeae. Of the 96 men who had non-gonococcal urethritis, 14 (14.6%) were
      infected with C. trachomatis, 16 (16.7%) with M. genitalium and only one with
      both microorganisms. In comparison, 15 (8.9%) of 169 men without overt urethritis
      and without N. gonorrhoeae were infected with C. trachomatis and 15 (8.9%) with
      M. genitalium, proportions that were about half the size of those in the group
      with overt urethritis.

PMID- 11972937
TI  - Syphilis, gonorrhoea and chlamydial infection among women undergoing legal or
      illegal abortion in Maputo.
AB  - Our objectives were to compare the prevalence of sexually transmitted infections
      (STIs) in 103 women undergoing induced legal abortion (LA) and in 101 women with
      confirmed, recent illegal abortion (IA), in Maputo, Mozambique. For the purpose
      of this study, LA was considered the abortion provided in the Maputo Central
      Hospital with the approval of the Ministry of Health, and IA the one not provided
      through the approved facility, mentioned above. Women with IA were recruited in
      the outpatient gynaecology ward and women with LA in the emergency gynaecology
      ward in the Maputo Central Hospital, during the same time period. Serological
      tests for syphilis (rapid plasma reagin, ELISA-IgG and fluorescent treponemal
      antibody absorption), gonorrhoea (indirect haemagglutination) and chlamydia
      (microimmunofluorescence) were carried out. Direct immunofluorescence for
      detection of Chlamydia trachomatis antigen was done on endocervical smears from
      all the women. The prevalence of syphilis seropositivity in IA women is twice
      that of LA women (odds ratio [OR] 2.13; 95% confidence interval [CI] 0.55-9.95),
      with 10.9% and 4.9%, respectively. Exposure to gonorrhoea in these 2 groups is
      similar (OR 1.18; 95% CI 0.63-2.20), with seroprevalence of 31.1% in the LA and
      34.7% in the IA group. The high titres are also similar in both groups. Serology
      findings for C. trachomatis indicate prevalence of seropositivity of 40.6% in the
      LA and 44.4% in the IA group with no significant difference (OR 1.17; 95% CI 0.64
      2.13). In conclusion, STIs are highly prevalent in both IA and LA groups in
      Maputo. Urgent interventions are needed to reduce their prevalence and
      consequently their adverse consequences.

PMID- 11972938
TI  - Relative risk of HIV infection among young men and women in a South African
      township.
AB  - The prevalence of HIV infection in Africa is substantially higher among young
      women than it is among young men. Biological explanations of this difference have
      been presented but there has been little exploration of social factors. In this
      paper we use data from Carletonville, South Africa to explore various social
      explanations for greater female infection rates. This paper reports on data from
      a random sample of 507 people between 13 and 24 years old. Subjects were tested
      for HIV, as well as other sexually transmitted infections (STIs), and answered a
      behavioural questionnaire. The age-prevalence of HIV infection differs between
      men and women with considerably higher rates of increase with age among young
      women. The age of sexual debut did not differ significantly between men and women
      (15.9 and 16.3 years, respectively) and below the age of 20 years there was no
      difference in the number or distribution of the number of sexual partners
      reported by men or women. The risk of infection per partnership was substantially
      higher among women than among men. Women have sexual partners who are, on
      average, about five years older than they are with some variation with age.
      Scaling the age-prevalence curve for men by the age of their sexual partners
      gives a curve whose shape is indistinguishable from that for women but is about
      30% lower for men than for women. In terms of social explanations for HIV rates
      among women, the data indicates that this difference can be explained by the
      relative age of sexual partners, but not by other factors explored. In addressing
      the epidemic among young women it will be essential to deal with the social
      factors that lead young women to select their partners from older-age cohorts and
      that shape their sexual networking patterns.

PMID- 11972939
TI  - Association of herpes simplex virus type 2 with the human immunodeficiency virus
      among urban women in Zimbabwe.
AB  - A cross-sectional study at two urban primary health care clinics in Zimbabwe was
      conducted among 393 consecutive women. The purpose was to determine the
      seroprevalence of herpes simplex virus type 2 (HSV-2), to identify coinfections
      and to determine the association between HSV-2, HIV and other sexually
      transmitted infections (STIs). Sera were tested for HSV-2, HIV and syphilis.
      Genital specimens were tested for the other STIs. The seroprevalence of
      ulcerative STIs tested was 42.2% for HSV-2 and 3.9% for syphilis. HSV-2
      seropositive women had twice the risk of being HIV infected compared to HSV-2
      seronegative women, adjusted OR=2.05 (95% CI=1.29-3.23). HSV-2 seropositivity was
      also associated with older age, a lower level of education, increase in the
      number of lifetime sexual partners and history of genital ulcers in the past six
      or more months. Our data suggest that in this population HSV-2 may contribute
      more to HIV infection than syphilis because of its high frequency. There is an
      urgent need for development of an effective HSV-2 vaccine.

PMID- 11972940
TI  - Topical imiquimod cream 5% for resistant perianal warts in a renal transplant
      patient.
AB  - Renal transplant recipients represent a patient subgroup for whom the effective
      treatment of genital warts poses a significant problem in genitourinary medicine.
      This case demonstrates the safe and effective treatment of resistant perianal
      warts in a male renal transplant recipient using imiquimod.

PMID- 11972941
TI  - A review of guidelines and standards for telemedicine.
AB  - We conducted a review to establish the range and scope of current telemedicine
      guidelines and standards. Published guidelines were identified by searching the
      Medline and Telemedicine Information Exchange (TIE) databases, and by performing
      a Google search using the term 'telemedicine guidelines'. Three types of
      guidelines were identified, namely clinical, operational and technical. Clinical
      guidelines included those for teleradiology, telepsychiatry, home telenursing,
      minor injuries telemedicine, surgical telemedicine, teledermatology and
      telepathology. Operational guidelines included those for email communication,
      Internet access and videoconferencing. Technical guidelines included those from
      the American Telemedicine Association and the US Office for the Advancement of
      Telehealth. The main standards relevant to telemedicine include those of the
      International Telecommunication Union and the DICOM standard. The scarcity of
      guidelines and standards suggests that telemedicine is not yet near to routine
      use. If an international telemedicine organization were to take responsibility
      for defining guidelines, under the direction of clinicians with appropriate
      telemedicine experience, this might speed up their development.

PMID- 11972942
TI  - User satisfaction with home telecare based on broadband communication.
AB  - Home telecare services based on broadband communication were established in five
      locations in Europe. Two different types of telecare unit were developed: one
      based on a PC or set-top box containing a videoconferencing codec and another on
      off-the-shelf videoconferencing units. The participants in the project were 13
      medical staff, 135 patients and 88 people informally caring for the patients.
      Questionnaires were used to evaluate user satisfaction with eight telecare
      services. Almost all participants rated the usability of the system as good or
      excellent. A total of 105 telecare sessions were scored by the medical staff.
      Overall, the quality of audio and video communication was judged satisfactory.
      For the patients and carers, the perceived quality of communication was also
      satisfactory and did not vary significantly between sites. The medical staff were
      reasonably satisfied with how the service supported them in their work. Except
      for the item about being able to support patients in a critical situation,
      medical staff agreed that an improved quality of health services was offered
      through telecare. All participants agreed that personal information was treated
      confidentially and that there was little risk in using the telecare services. The
      medical staff trusted the assessments they could make remotely while using the
      telecare system. Although the findings cannot be generalized due to the small
      number of telecare sessions and the relatively short duration of the experiment,
      the results encourage further research.

PMID- 11972943
TI  - Randomized comparison of the quality of realtime fetal ultrasound images
      transmitted by ISDN and by IP videoconferencing.
AB  - We compared the quality of realtime fetal ultrasound images transmitted using
      ISDN and IP networks. Four experienced obstetric ultrasound specialists viewed
      standard recordings in a randomized trial and rated the appearance of 30 fetal
      anatomical landmarks, each on a seven-point scale. A total of 12 evaluations were
      performed for various combinations of bandwidths (128, 384 or 768 kbit/s) and
      networks (ISDN or IP). The intraobserver coefficient of variation was 2.9%, 5.0%,
      12.7% and 14.7% for the four observers. The mean overall ratings by each of the
      four observers were 4.6, 4.8, 5.0 and 5.3, respectively (a rating of 4 indicated
      satisfactory visualization and 7 indicated as good as the original recording).
      Analysis of variance showed that there were no significant interobserver
      variations nor significant differences in the mean scores for the different types
      of videoconferencing machines used. The most significant variable affecting the
      mean score was the bandwidth used. For ISDN, the mean score was 3.7 at 128
      kbit/s, which was significantly worse than the mean score of 4.9 at 384 kbit/s,
      which was in turn significantly worse than the mean score of 5.9 at 768 kbit/s.
      The mean score for transmission using IP was about 0.5 points lower than that
      using ISDN across all the different bandwidths, but the differences were not
      significant. It appears that IP transmission in a private (non-shared) network is
      an acceptable alternative to ISDN for fetal tele-ultrasound and one deserving
      further study.

PMID- 11972944
TI  - The role of telecardiology in supporting the decision-making process of general
      practitioners during the management of patients with suspected cardiac events.
AB  - We studied the role of telecardiology in reducing unnecessary hospital admissions
      of patients with suspected life-threatening cardiac events (CEs), evaluated by
      general practitioners (GPs). Over one month, 456 consecutive patients (mean age
      65 years, SD 19) complaining of typical (10%) or atypical (42%) chest pain,
      palpitations (19%), dyspnoea (19%) or syncope (10%) were enrolled. Before
      teleconsultation, the GPs recorded their own opinion (based on clinical
      evaluation only) about the presence of a CE. Following transmission of the
      electrocardiogram (ECG), this opinion was compared with that of the cardiologist.
      In total there was agreement between the GP and cardiologist about the presence
      of a CE in 316 of the patients (69%) and disagreement in 140 patients (31%). This
      represents a specificity and sensitivity of the GPs' diagnosis of 76% and 47%,
      respectively. For 84 of 134 patients judged as having a CE by the GP,
      telecardiology avoided hospitalization; on the other hand, telecardiology
      identified a CE in 56 of 322 patients judged as not having a CE by the GP.
      Telecardiology is a useful tool with which to reduce unnecessary hospitalizations
      in patients with suspected life-threatening CEs.

PMID- 11972945
TI  - Teleconsultation as a replacement for referral to an outpatient clinic.
AB  - We conducted a randomized case control study of referrals from a primary care
      centre in Finland. All the consultations and referrals from seven general
      practitioners (GPs) dealt with by internists and surgeons at Satakunta Central
      Hospital in Pori and geriatricians at Satalinna Hospital in Harjavalta over five
      months were included. For patients in the control group, a conventional referral
      letter was sent to the hospital outpatient clinic. For patients in the
      intervention group, the GPs had to decide whether they wanted an electronic
      consultation with the hospital or wanted to refer the patient (i.e. to transfer
      responsibility for treatment). Communication with the hospital specialist was
      then via a secure Web-based system. Ninety-three patients consented to
      participate in the study. None refused, although there were 15 non-attenders.
      Satisfaction data were collected from questionnaires completed by the patients
      and doctors. All the patients treated by teleconsultation said that they wanted
      the same procedure in future and 63% of the control group said they would prefer
      a teleconsultation next time. The doctors quickly learned to exploit the
      telemedicine model successfully. The responsibility for treatment was maintained
      in the health centre in 52% of cases using teleconsultation, without any visit to
      hospital being required. The GPs and the hospital doctors agreed on the follow-up
      treatment. Telereferral increased the possibility of the GP maintaining
      responsibility for the treatment. The reduced number of hospital visits in the
      telemedicine model should produce significant cost savings.

PMID- 11972946
TI  - Learning in organizations working with telemedicine.
AB  - To investigate learning in telemedicine, qualitative interviews were conducted
      with 30 people working with telepsychiatry, teledermatology, a telepathology
      frozen-section service and tele-otolaryngology. More than 80% of the respondents
      said that they had learnt something new by using telemedicine. Most frequently
      the participants improved their knowledge of the specialty in which they were
      involved, but this was not the only way in which they learnt. The learning did
      not necessarily change behaviour, as two-thirds of the respondents felt that the
      learning had not permitted them to perform tasks for which they had previously
      needed assistance (although this varied somewhat with the type of telemedical
      work that respondents were engaged in). Two-thirds of respondents thought that
      something more could be done in telemedical work to promote their own learning,
      which shows the clear potential for learning by telemedicine. Learning could be
      promoted further by extending the use of the technology to other applications. To
      start working with telemedicine, initial instruction seems to be sufficient--a
      more extensive training programme appears unnecessary. In future, as many
      applications of telemedicine are implemented, health-care organizations may
      become important arenas for learning and leaders will have to focus on learning.
      The results of the present study clearly showed that working with telemedicine
      produces learning.

PMID- 11972947
TI  - The multidisciplinary management of a paediatric cardiac emergency.

PMID- 11972949
TI  - A versatile and economical method of image capture for telepathology.

PMID- 11972948
TI  - Emergency care in a remote area using interactive video technology: a study in
      prehospital telemedicine.

PMID- 11972950
TI  - Origin and molecular specification of oligodendrocytes in the telencephalon.
AB  - Previous studies have demonstrated that oligodendrocytes in the spinal cord and
      brainstem originate from restricted domains of ventral neuroepithelium under the
      influence of sonic hedgehog protein (SHH). However, the origin of
      oligodendrocytes in the telencephalon, the most anterior part of the CNS, has not
      been established. A recent study has precisely mapped the origin of telencephalic
      oligodendrocytes to a small region of the ventral telencephalon in rodents, and
      has presented evidence that telencephalic oligodendrogenesis is, like that of the
      spinal cord, under the influence of SHH signaling.

PMID- 11972951
TI  - Where, oh where, have my stem cells gone?
AB  - During the summer of 2001, Americans were treated to high political drama
      courtesy of the debate over embryonic and adult stem cell research. The popular
      press was flush with predictions about how neural stem cells would reverse,
      almost by magic, the devastation caused by diseases such as Alzheimer's,
      Parkinson's, stroke or spinal cord injury. Unfortunately, this promise remains
      unfulfilled because we have such a poor understanding of how stem cells function.
      With regard to adult stem cells, we are not even completely sure where they are,
      or how or when they got there. A provocative study by Ourednik et al. published
      in Science suggests that in primates, adult neural stem cells are allocated
      during early corticogenesis. The study also provides evidence for the existence
      of stem cells dispersed throughout the frontal cortex and striatum.

PMID- 11972952
TI  - Stereotypy in neocortical microcircuits.
AB  - A central debate regarding neocortical function concerns the degree to which the
      underlying microcircuitry is stereotypically organized. Stereotypy reflects
      invariance in structure and function, as a result of common genetic templates and
      environmental conditions, whereas uniqueness can be caused by genetic variations,
      differences in environmental conditions as well as random processes. Stereotypy
      is an appealing concept because it provides strong support for determinism in the
      formation of neuronal microcircuits and in the relationship between their
      specific structure and function.

PMID- 11972958
TI  - Radial glia: multi-purpose cells for vertebrate brain development.
AB  - Radial glia are specialized cells in the developing nervous system of all
      vertebrates, and are characterized by long radial processes. These processes
      facilitate the best known function of radial glia: guiding the radial migration
      of newborn neurons from the ventricular zone to the mantle regions. Recent data
      indicate further important roles for these cells as ubiquitous precursors that
      generate neurons and glia, and as key elements in patterning and region-specific
      differentiation of the CNS. Thus, from being regarded mainly as support cells,
      radial glia have emerged as multi-purpose cells involved in most aspects of brain
      development.

PMID- 11972959
TI  - Ephrins are not only unattractive.
AB  - The ephrins and their Eph receptors have emerged as repulsive cues for growing
      axons during the past decade. Since then, great effort has been made to
      understand the significance and mechanisms of Eph-mediated repulsion. More
      recently, it has become clear that ephrins perform in many more developmental
      processes than the repulsion-dependent establishment of topography in the nervous
      system. As numerous studies suggest functions more akin to adhesion or attraction
      than to repulsion, increasing attention is now being paid to the intracellular
      mechanisms that might explain this duality.

PMID- 11972960
TI  - Molecular mechanisms of CNS synaptogenesis.
AB  - Synapses of the mammalian CNS are asymmetric sites of cell-cell adhesion between
      nerve cells. They are designed to mediate the rapid and efficient transmission of
      signals from the presynaptic bouton of one neuron to the postsynaptic plasma
      membrane of a second neuron. Significant progress has been made in the
      characterization of the structural, functional and developmental assembly of CNS
      synapses. Recent progress has been made in understanding the molecular and
      cellular mechanisms that underlie synaptogenesis, in particular that of
      glutamatergic synapses of the CNS.

PMID- 11972962
TI  - NaN/Nav1.9: a sodium channel with unique properties.
AB  - The Na(v)1.9 Na(+) channel (also known as NaN) is preferentially expressed in
      nociceptive neurons of the dorsal root ganglia (DRG) and trigeminal ganglia.
      Na(v)1.9 produces a persistent, tetrodotoxin-resistant current with wide overlap
      between activation and steady-state inactivation, and appears to modulate resting
      potential and to amplify small depolarizations. These unique properties indicate
      that Na(v)1.9 has significant effects on the electroresponsive properties of
      primary nociceptive neurons. Downregulation of Na(v)1.9, which results from a
      lack of peripheral glial cell-derived neurotrophic factor following peripheral
      axotomy, might retune DRG neurons and contribute to their hyperexcitability after
      nerve injury. Thus, Na(v)1.9 appears to play a key role in nociception and is an
      attractive target in the search for more effective treatments for pain.

PMID- 11972963
TI  - Boundary formation in the hindbrain: Eph only it were simple...
AB  - Segmentation of the vertebrate hindbrain into rhombomeres is a key step in the
      development of a complex pattern of differentiated neurons from a homogeneous
      neuroepithelium. Many of the transcription factors important for establishing the
      segmental plan and assigning rhombomere identity are now known. However, the
      downstream effectors that bring about the formation of rhombomere boundaries are
      only just being characterized. Here we discuss molecules that could be
      responsible for segregating populations of cells from different rhombomeres. We
      focus on recent work demonstrating that the Eph family of receptor tyrosine
      kinases and their ligands, the ephrins, function in rhombomere-specific cell
      sorting and initiation of a structural boundary. We discuss the contributions of
      two mechanisms -- cell sorting and plasticity -- to the formation of rhombomere
      boundaries.

PMID- 11972964
TI  - A Canadian experiment: the Institute of Neurosciences, Mental Health and
      Addiction. How to link up the brain via a virtual institute.
AB  - In June 2000, the Canadian government abolished the Medical Research Council of
      Canada, creating the Canadian Institutes of Health Research (CIHR) and appointing
      the internationally renowned geneticist Alan Bernstein as its first president.
      Bernstein and the CIHR Governing Council then elaborated the novel concept of 13
      'virtual' CIHR institutes (see http://www.cihr.ca for further information). These
      institutes are not physical entities, but virtual organizations aiming to support
      researchers located in universities, hospitals and research centres across
      Canada. Following an open competition, December 2000 saw the appointment of a
      scientific director to lead the development of each institute. Remi Quirion, a
      neuroscientist and Professor of Psychiatry based at the Douglas Hospital Research
      Centre of McGill University (Montreal, Canada) is the first Scientific Director
      of the Institute of Neurosciences, Mental Health and Addiction (INMHA). Here he
      summarizes the early developments and initiatives undertaken by his institute.

PMID- 11972965
TI  - A bug's smell--research into insect olfaction.
AB  - The olfactory system has become an important model system for neurobiological
      function and sensory processing. In insects, odours play a vital role in all
      aspects of life. From the late 1950s until very recently, research into the
      structure and function of the insect olfactory system has often preceded similar
      investigations in vertebrates and has been important in the formulation of
      general principles.

PMID- 11972968
TI  - Are we giving too many doses of hepatitis A and B vaccines?
AB  - The immune response of an inactivated hepatitis A vaccine given to middle aged
      travellers 4-6 years after one single, primary dose was recently studied. All 25
      vaccinees showed an impressive anamnestic booster response (GMT 2.993mIU/ml). The
      study confirms one previous report as well as experimental data, indicating a
      long-term proliferative T-cell response following one single primary dose of
      Havrix 1440. In 1999, Wistrom et al. demonstrated that a booster 4 years after
      priming medical students with one single dose of a recombinant HB vaccine
      disclosed a rapid antibody response indicating a well-preserved memory. These
      reports put in focus the question: are we routinely offering too many doses of
      hepatitis A and B vaccines?

PMID- 11972969
TI  - Post-exposure rabies treatment in pigs.
AB  - A rabid dog invaded a Thai pig farm and severely mauled 11 adult pigs. This
      offered an opportunity to study efficacy of a human type post-exposure vaccine
      regimen with and without rabies immunoglobulin. A commercial veterinary tissue
      culture rabies vaccine and equine rabies immune globulin were used. All pigs
      survived for 1 year following the exposure. All animals developed detectable
      rabies neutralizing antibodies on day 7 and levels over 0.5IU/ml on day 14. This
      small study suggests that post-exposure rabies treatment using a proven human
      regimen, applied to valuable farm animals, can be safe and effective.

PMID- 11972970
TI  - Priming of measles virus-specific humoral- and cellular-immune responses in
      macaques by DNA vaccination.
AB  - Although the currently used live attenuated measles vaccines are safe and
      effective, they are dependent on cold chain maintenance and are often ineffective
      in young infants due to interference by maternal antibody. Therefore, besides
      vector-based vaccines, different new generation non-replicating candidate measles
      vaccines are being considered, including nucleic acid vaccines. We have
      vaccinated cynomolgus macaques transdermally with DNA plasmids encoding measles
      virus (MV) proteins. Following two vaccinations, low serum antibody responses
      were detected. Wild-type measles virus challenge 1 year after vaccination showed
      reduced viraemia in some animals. However, accelerated humoral- and cellular
      immune responses were observed in all vaccinated macaques, demonstrating
      successful priming by the DNA vaccines.

PMID- 11972971
TI  - Immunization against dental caries.
AB  - Dental caries is one of the most common infectious diseases. Of the oral
      bacteria, mutans streptococci, such as Streptococcus mutans and S. sobrinus, are
      considered to be causative agents of dental caries in humans. There have been
      numerous studies of the immunology of mutans streptococci. To control dental
      caries, dental caries vaccines have been produced using various cell-surface
      antigens of these organisms. Progress in recombinant DNA technology and peptide
      synthesis has been applied to the development of recombinant and synthetic
      peptide vaccines to control dental caries. Significant protective effects against
      dental caries have been shown in experimental animals, such as mice, rats and
      monkeys, which have been subcutaneously, orally, or intranasally immunized with
      these antigens. Only a few studies, however, have examined the efficacy of dental
      caries vaccines in humans. Recently, local passive immunization using murine
      monoclonal antibodies, transgenic plant antibodies, egg-yolk antibodies, and
      bovine milk antibodies to antigens of mutans streptococci have been used to
      control the colonization of the organisms and the induction of dental caries in
      human. Such immunization procedures may be a safer approach for controlling human
      dental caries than active immunization.

PMID- 11972972
TI  - DNA vaccination of ferrets with chimeric influenza A virus hemagglutinin (H3)
      genes.
AB  - Recently a technology was established based on homologous recombination that
      allowed the rapid generation of chimeric HA genes of influenza viruses,
      containing the antigenic determinants obtained from various influenza virus A
      (H3N2) viruses. In the present report plasmids were generated using a H3 HA
      vector handle and the hypervariable regions of two genetically distinct influenza
      A H3N2 viruses, A/Stockholm/7/97 and A/Netherlands/18/94. In a ferret model it
      was shown that immunisation with plasmid DNA encoding chimeric HA indeed elicited
      antibody responses specific for the virus from which the hypervariable region
      with the antigenic determinants were obtained. After DNA-immunisation of the
      ferrets, protective immunity against infection with influenza virus
      A/Netherlands/18/94 was evaluated.

PMID- 11972973
TI  - Elimination of luteinizing hormone cross-reactive epitopes from human chorionic
      gonadotropin.
AB  - The beta-chain of human chorionic gonadotropin (hCG) has been shown to have
      efficacy in clinical trials when used as a contraceptive vaccine. This hormone is
      a heterodimer, the alpha-chain being shared with the other members of the
      glycoprotein hormone family but the beta-chain being unique to hCG. Nevertheless,
      there is sequence homology between the hCG beta-chain and the beta-chain of human
      luteinizing hormone (hLH) which results in cross-reactive antibodies being
      produced following immunization with wild-type hCGbeta. To reduce or eliminate
      such cross-reactions we generated a number of mutants of the hCGbeta-chain. One
      mutant (hCGbeta(R68E)), containing an arginine to glutamic acid replacement at
      position 68, has been expressed as a recombinant protein in High Five insect
      cells. The recombinant BAChCGbeta(R68E) form of this molecule was used to
      immunize rabbits and the antibody response compared to the response following
      immunization with the recombinant wild-type protein BAChCGbeta and with the
      native hCGalphabeta heterodimer isolated from pregnancy urine. The mutant
      elicited the production of antibodies which avidly recognize native hCG. Compared
      to immunization with wild-type hCG, the response showed very little cross
      reactivity with hLH. This is demonstrated to be due to a radically altered
      epitope usage in the response to the mutant, which now focuses mainly upon the C
      terminal region of the beta-chain.

PMID- 11972974
TI  - Stratified and cryogenically stored (SACS) vaccines, a new concept in emergency
      foot-and-mouth disease vaccine formulation and storage.
AB  - Strategic reserves of foot-and-mouth disease (FMD) antigen have become an
      integral part of FMD control policy for many countries. They are based on two
      principles, ready formulated vaccine stored at +4 degrees C, or concentrated
      antigen preparations held at ultra-low temperature for later formulation.
      However, the latter is more economical, since ready formulated vaccine, based on
      oil or aluminium hydroxide/saponin adjuvants, requires regular replacement. This
      is primarily the result of the vaccine's limited shelf-life, nominally 18 months
      at +4 degrees C. Unfortunately, lowering the temperature of storage, in a bid to
      extend its shelf-life, has a detrimental effect on the vaccine's potency.
      Montanide ISA 206 and 25, two 'ready-to-formulate' oil adjuvants which can be
      used in all target species, are ideal for emergency vaccination. Their potential
      is enhanced by the ease in which they are formulated into oil emulsion vaccines.
      Here we describe a novel approach of layering the individual components of FMD
      vaccine in the same primary container and then storing the product at ultra-low
      temperature. This avoids the detrimental effect on potency, normally observed
      with frozen formulated FMD vaccine, and could substantially extend the products
      shelf-life. The implications of this approach for emergency vaccination strategy
      are discussed.

PMID- 11972975
TI  - Central demyelinating disorders and hepatitis B vaccination: a risk-benefit
      approach for pre-adolescent vaccination in France.
AB  - The objective of the study was to provide immunization policy decision makers
      with a risk-benefit analysis for pre-adolescents vaccination, for various
      scenarios regarding the existence and the strength of an association between
      hepatitis B vaccination and the occurrence of first episode of central
      demyelinating (FECD) disease. The risks were assessed as the attributable risks
      of FECD for various time intervals between vaccination and onset of FECD and the
      benefits as the number of acute fulminant hepatitis B and cirrhosis prevented in
      a vaccinated annual cohort. Even in the worst-case considered, the number of
      complications prevented by the vaccination outweighs quantitatively the potential
      risks. Even if both sides of the balance are of different medical and
      sociological nature, this result is in favor of reinforcing the pre-adolescent
      vaccination strategy in France.

PMID- 11972976
TI  - 200 Gy sterilised Toxoplasma gondii tachyzoites maintain metabolic functions and
      mammalian cell invasion, eliciting cellular immunity and cytokine response
      similar to natural infection in mice.
AB  - 200Gy gamma-irradiated Toxoplasma gondii RH tachyzoites failed to reproduce in
      vitro and in vivo. In short-term cultures, these parasites maintained a
      respiratory response, the ability to invade cells and preserved protein and
      nucleic acid synthesis. ELISA and Western blotting techniques demonstrated the
      similarity in humoral response between mice infected with gamma-irradiated
      tachyzoites and animals infected with naive parasites and treated with
      sulfadoxine, higher than mice immunised with formaldehyde-killed tachyzoites.
      Splenocyte stimulation by T. gondii antigen produced lymphoproliferative response
      and cytokine profile (IL-10, IL-12, IFN-gamma and TNF-alpha) similar to those
      produced by chronic natural infection. Mice immunised with irradiated tachyzoites
      had extended survival times after subsequent tachyzoite challenge, and displayed
      minimal cerebral pathology after cyst challenge. Irradiated tachyzoites lose
      their reproductive ability whilst maintaining metabolic function and may provide
      a novel tool for the study of toxoplasmosis and vaccine development.

PMID- 11972977
TI  - Preparation and characterisation of attenuated cold-adapted influenza A
      reassortants derived from the A/Leningrad/134/17/57 donor strain.
AB  - The development of a rapid cell culture method for the preparation of cold
      adapted (ca) influenza A reassortant viruses is described and compared with a
      currently used egg method. Mixtures of the ca donor A/Leningrad/134/17/57-ca
      (A/Len/17) and A/Beijing/32/92 (A/Beij/32), a recent H3N2 epidemic strain, were
      used to co-infect chicken embryo kidney (CEK) cell cultures; reassortant progeny
      were selected using an infectious centre assay. The assay was capable of
      detecting interference where the infectivity ratio for A/Len/17 and A/Beij/32 was
      1:7. Progeny viruses were characterised genetically by amplification of defined
      regions within each of the six internal genes by PCR and identification of the
      products by restriction enzyme analysis. Reassortants were also tested for ca and
      temperature-sensitive (ts) phenotype and the identity of the surface antigens.
      The infectious centre assay was shown to be an effective method for isolating
      reassortant progeny that possessed the haemagglutinin and neuraminidase surface
      antigens of A/Beij/32. Reassortants with the six internal genes derived from the
      donor strain and possessing the ca and ts phenotype were readily obtained when
      (a) an infectivity ratio of 1:49 was used and (b) two plaque-to-plaque isolations
      of progeny virus were made after growth at 25 degrees C and one at 34 degrees C,
      both in the presence of antiserum to the donor strain.

PMID- 11972978
TI  - Phytosecretion of enteropathogenic Escherichia coli pilin subunit A in transgenic
      tobacco and its suitability for early life vaccinology.
AB  - A plant expression cassette system was engineered to efficiently target proteins
      to the default secretory pathway, allowing the expression of DNA inserts in three
      frames as fusion proteins containing a synthetic tobacco calreticulin cleavable
      signal peptide sequence, with the advantage of producing the recombinant proteins
      by phytosecretion. As one approach to develop a vaccine to enteropathogenic
      Escherichia coli (EPEC) infection, the oral immunogenicity of phytosecreted BfpA,
      the structural subunit A of the bundle-forming pilus, expressed at high levels
      (7.7% of soluble protein) in transgenic tobacco tissues, was demonstrated in
      BALB/c mice by the induction and detection of fecal anti-BfpA antibodies.

PMID- 11972979
TI  - Immunogenicity and reactogenicity of a combined high dose hepatitis A and
      hepatitis B vaccine, compared to that of Twinrix in healthy Indian children.
AB  - BACKGROUND AND AIMS: Hepatitis A virus (HAV) and hepatitis B virus (HBV) are
      vaccine preventable important childhood acquired infectious diseases in
      developing countries. In the changing epidemiology of HAV, the utility of such a
      vaccine in India needs urgent attention. Further, the efficacy of two versus
      three dose schedule needs to be assessed to improve compliance. SUBJECTS AND
      METHODS: One hundred healthy school children, aged 1-15 years were recruited in a
      randomised open study to receive either vaccination schedule: Group I: combined
      high-dose hepatitis A and B vaccine to be administered on a 0, 6 month schedule
      intramuscularly; Group II: to be administered on 0, 1, 6 month Twinrix
      (GlaxoSmithKline Biologicals, Rixensart, Belgium) schedule intramuscularly. The
      seroconversion (> or =1MIU/ml for anti-HBs antibodies and > or =33MIU/ml for anti
      HAV antibodies) and seroprotection (anti-HBs > or =10MIU/ml after the third dose
      of vaccine) rates were determined at months 1, 2, and 7. RESULTS: The mean age
      and gender was similar between groups: 7.9+/-2.6 years (range 3-15 years). At
      month 7 all subjects (100%) in both groups were seropositive for anti-HAV
      antibodies, Group I had higher anti-HAV titres at months 1 or 2 compared to Group
      II (P=0.025, P=0.040). Group II developed higher seroprotection rates (month 2,
      P=0.002, month 6, P=0.003) compared to Group I and higher titres (month 2,
      P=0.001, month 6 P=0.001) compared to Group I. At month 7, the geometric mean
      titres (GMTs) were comparable between groups and seroprotection reached 100% in
      both the groups. The incidence of any symptom per dose analysis reported during a
      4-day follow-up period was significantly higher in Group I, 53% (52/98) of the
      documented doses compared to 37% (54/146) in Group II (P=0.018). CONCLUSION:
      Twinrix vaccine is safe and highly immunogenic in Indian children. Further study
      of the high dose vaccine would determine if its two dose regimen is a feasible
      advantage.

PMID- 11972980
TI  - Antibody response to a delayed booster dose of anthrax vaccine and botulinum
      toxoid.
AB  - We evaluated the prevalence and concentration of serum antibodies 18-24 months
      after primary inoculation with anthrax and botulinum vaccines, and assessed the
      reactogenicity and immunogenicity of a significantly delayed booster dose of
      these vaccines. Five hundred and eight male active-duty military personnel
      received one, two or three inoculations with anthrax vaccine and/or botulinum
      toxoid in 1990/1991 in preparation for Operations Desert Shield/Desert Storm.
      Subjects were vaccinated with the licensed anthrax vaccine, adsorbed (AVA) and
      pentavalent (ABCDE) botulinum toxoid (PBT) BB-IND 3723. Anthrax protective
      antigen (PA) IgG antibody was measured in serum using an immunocapture enzyme
      linked immunosorbent assay (ELISA). A mouse neutralization test was used to
      determine the titer of Clostridium botulinum type A antitoxin in serum samples.
      The prevalence of anti-PA IgG was 30% in individuals 18-24 months after priming
      with one, two or three doses of AVA. After boosting, 99% of volunteers had
      detectable anti-PA IgG; only two individuals failed to respond. The prevalence of
      antibodies against botulinum toxin type A was 28% 18-24 months after initial
      priming. Following boosting, 99% of volunteers had serum titers >0.02IU/ml, and
      97% responded with titers > or =0.25IU/ml. Systemic reactions to booster
      vaccinations could not be specifically ascribed to one or the other vaccine, but
      were generally mild and of brief duration. Forty-five percent of volunteers
      reported one or more systemic reactions over the course of 7 days. Injection site
      reactions of any kind occurred in 25% of AVA recipients and in 16% of PBT
      recipients; persistence of local reactions beyond 7 days was infrequent. While
      the kinetics and durability of immune responses must be studied, these findings
      suggest that booster doses of anthrax vaccine and botulinum toxoid sufficient to
      stimulate a robust anamnestic response may be given at times distant from receipt
      of the primary inoculations.

PMID- 11972982
TI  - Molecular surveillance of HIV-1 field strains in Nigeria in preparation for
      vaccine trials.
AB  - We conducted a national molecular epidemiologic survey of HIV-1 strains in
      Nigeria to determine the most prevalent subtype(s) for use in developing
      candidate vaccines. A total of 230 HIV-1-positive blood samples collected from 34
      of the 36 Nigerian states were analyzed by our modified env gp41-based
      heteroduplex mobility assay (HMA) and/or gp41 sequencing and analysis. Overall,
      103 (44.8%) were subtype A, 125 (54.3%) were subtype G, one (0.4%) was subtype C,
      and one (0.4%) was subtype J, and one (0.4%) was unclassifiable. To further
      characterize Nigerian viruses to aid in strain selection for candidate vaccines,
      one gp41 subtype G and five gp41 subtype A strains were selected for full
      envelope sequencing. The one subtype G sequence had consistent phylogenies
      throughout gp160, using programs to detect recombination. However, all five
      sequences that were primarily subtype A in gp41 were found to be recombinant
      viruses. Two of the five (40%) were A/G/J mosaics with common breakpoints. The
      remaining three gp160 recombinants all had their own unique break points: two A/?
      and one A/?/G, however, all five had the majority of their mosaic breakpoints
      occurring in gp41. None of the five were consistent with the circulating
      recombinant form (CRF)02_AG strain previously reported to be prevalent in West
      Africa. In conclusion, we showed a clear dominance and widespread distribution of
      gp41 subtypes A and G in fairly equal proportions, suggesting that vaccines
      designed for use in this geographic locale should incorporate the gene(s) of both
      subtypes. However, appreciating the magnitude of diversity of HIV-1 strains in
      Nigeria may require sequencing and analysis of longer gene regions for the
      identification of prevalent or emerging CRFs.

PMID- 11972981
TI  - The induction of systemic and mucosal immunity to protein vaccines delivered
      through skin sites exposed to UVB.
AB  - It has been reported that common mucosal immunity can be efficiently induced in
      mice following immunization through the skin with vaccine formulations containing
      either the active form of vitamin D, or chemical agents capable of locally
      enhancing cyclic adenosine monophosphate levels. Herein, we report that exposure
      of skin to ultraviolet radiation B (UVB) can be employed as a means to alter
      systemic humoral immune responses and to promote the induction of mucosal
      immunity to protein antigens delivered into UVB-exposed skin sites. Our data
      indicates that the skin, as a vaccination site, can be manipulated to allow
      efficient induction of common mucosal and systemic immune responses.

PMID- 11972983
TI  - Smallpox vaccination techniques; from knives and forks to needles and pins.
AB  - Factors affecting the development of smallpox vaccination techniques are
      discussed and 11 different techniques for inoculating the vaccine are identified
      and described. The earliest, the simple cut or scratch, was already widely used
      for smallpox inoculation (variolation). Later, when it became evident that
      Jenner's claim of lifelong protection was not being achieved parallel, cross
      hatched and rotatory methods which produced more severe reactions were
      introduced, often at more than one site. These methods were then discontinued and
      even prohibited in some countries, when improved vaccine quality resulted in
      excessively-severe reactions with such techniques. They were replaced by improved
      methods such as multiple pressure and multiple puncture with the bifurcated
      needle, both of which were used extensively. However, the simple scratch method
      remained popular until the end of the vaccination era. Although the instruments
      used are not discussed in detail, representative examples of the wide variety
      used at various times and for the various techniques are illustrated. Again, the
      simplest and earliest designs remained in use throughout.

PMID- 11972986
TI  - Adverse effects of immunotherapeutics involving the immune system.
AB  - Immunotherapeutics are pharmaceutical products intended to modify immune
      functions either directly or indirectly by influencing physiological systems that
      affect immunological functions. They include conventional immunosuppressants,
      monoclonal antibodies, recombinant cytokines, gene therapy products or
      therapeutic vaccines. A variety of adverse effects involving the immune system
      have been described in laboratory animals as well as in the clinic. Some of these
      adverse effects can be predicted, at least to some extent, from the
      immunopharmacological profile of these drugs, but a number of unpredicted adverse
      effects have been described. Immunosuppression, allergy, autoimmunity,
      immunoactivation are the major adverse consequences to be expected as illustrated
      by this overview of the leading immunotherapeutics already used in the clinic.
      These untoward and potentially severe consequences support the need for a careful
      preclinical and clinical evaluation of the immunotoxicity of these products.

PMID- 11972987
TI  - Preclinical evaluation of gene transfer products: safety and immunological
      aspects.
AB  - As any new drug in development, gene transfer products have to be tested for
      their potential toxicity in preclinical studies. Strategies for preclinical
      safety evaluation of gene transfer compounds are similar to those undertaken for
      biotechnology-derived pharmaceuticals with the added complexity of having to test
      additional components, such as the vector and genetic material. Some
      recommendations have been issued by regulatory agencies to provide assistance in
      the toxicological assessment of gene transfer products before administration to
      humans. However, the design of such studies is complicated and has to be
      approached case-by-case. Crucial aspects for safety evaluation are: (1) the
      choice of animal models with respect to the pharmacological activity of the gene
      transfer product, the susceptibility to infection in the case of viral vectors,
      and to the immunogenicity of all entities; (2) biodistribution of the vector
      after administration, avoiding germinal transmission. Immunological and
      immunotoxicity endpoints should also be assessed. This paper reviews some of the
      properties of gene transfer vectors with emphasis on their potential effects on
      the immune system, and also highlights some of the problems likely to be
      encountered during the preclinical safety evaluation.

PMID- 11972988
TI  - Preclinical safety evaluation of monoclonal antibodies.
AB  - Monoclonal antibodies (mAbs) can be potent and specific therapeutics with long
      plasma half-lives and therefore long exposure times, which are now being
      clinically used to treat chronic disorders. Their recombinant design means some
      of their behaviours in the clinic can be determined at the design stage. However,
      their specific nature means a flexible approach often is required for preclinical
      studies and the use of novel approaches including parallel reagents and specific
      transgenic mice are being used. The key aspects at this level to consider are the
      effects on safety pharmacology and long-term immune status in the preclinical
      species used in order to predict to people the likely result of chronic clinical
      usage.

PMID- 11972989
TI  - Nonclinical evaluation of therapeutic cytokines: immunotoxicologic issues.
AB  - Cytokines are a diverse family of immunoregulatory proteins whose function has
      been the focus of intensive research for the past 25 years. Modern molecular
      biology techniques have resulted in production of these proteins in quantities
      sufficient to consider them as candidates for drug development. Due to the often
      pleiotropic nature of their action, in order to design meaningful nonclinical
      safety assessment studies, the practicing toxicologist must be able to
      differentiate between an exaggerated, but expected pharmacologic response and
      toxicity associated with their administration. Species specificity,
      nontraditional dose-response relationships, antigenicity, and unanticipated
      immunotoxicity are a few issues that must be considered when designing study
      protocols and interpreting data. In addition, despite validated methodology to
      examine the immune system as a potential target organ for toxicity, limitations
      exist in the ability to predict the autoimmune and allergenic potential of
      proteins such as these. Despite these challenges and limitations, over the past
      decade, many of these molecules have found clinical utility to treat a wide
      variety of diseases.

PMID- 11972990
TI  - Non-clinical vaccine safety assessment.
AB  - As vaccines are undoubtedly classified as pharmaceuticals, they have to be
      submitted to strict non-clinical safety evaluation. The context of their
      prophylactic use requires that every effort is made to ensure their safe use.
      Their safety evaluation is complex as they act through a multistage mechanism in
      which the vaccine by itself acts as a pro-drug, antibodies and activated
      lymphocytes being the actual effectors. Therefore, several potential toxicities
      must be considered: direct toxicity of the test article, toxicity linked to the
      pharmacodynamic activity of the vaccine, activation of pre-existing disorders,
      toxicity of contaminants and impurities and other adverse reactions due to
      interaction between the various components. Guidelines dealing with vaccines
      include general guidelines applicable to all pharmaceuticals, such as ICH S6, and
      also more specific documents which allow some flexibility in study design. Among
      the various studies, if single-dose studies are generally part of the quality
      control test battery, repeated dose studies are pivotal. The animal model and
      treatment schedule selection and the parameters investigated are critical for the
      relevance of this safety assessment. Immunological and safety pharmacology
      parameters should be adapted to the specific properties of vaccines and added to
      this type of study. Vaccines intended for pregnant women or women of child
      bearing age require embryo-fetal and post-natal studies with an adapted design to
      obtain appropriate fetal and maternal exposure during gestation with continuation
      into the post-natal period. Tests exist to detect hypersensitivity or autoimmune
      reactions, but require further validation. In addition to this tailor-made
      approach, any adjuvant or active component added to the vaccine formulation
      necessitate their own assessment using studies routinely performed for new drugs.
      From this review, vaccine toxicology would appear to be a separate discipline on
      its own whose predictivity will be increased by new method development.

PMID- 11972991
TI  - Vaccines: predicting the risk of allergy and autoimmunity.
AB  - The field of vaccines is markedly evolving with the introduction and development
      of many new concepts and formulations, as well as new indications. Based on the
      current clinical experience, vaccines can be considered safe in most cases.
      Nevertheless, allergy and, to a lesser extent, autoimmunity have repeatedly been
      described or suspected as rare adverse consequences of human vaccines. The
      mechanisms of these adverse reactions are ill-elucidated, if at all. No animal
      models have been adequately standardized and validated to predict the risk of
      allergy and autoimmunity associated with vaccines. However, a number of existing
      models can be considered for use, but need refinement to be applied to vaccine
      evaluation. Finally, because the preclinical safety evaluation has not received
      much attention in the past, efforts should be paid to design specific and cost
      effective procedures to meet the current expectations.

PMID- 11972992
TI  - Preclinical assessment of anti-CD40 Mab 5D12 in cynomolgus monkeys.
AB  - Monoclonal antibody (Mab) 5D12 is a potent antagonist of the CD40-CD40L pathway.
      This cellular interaction has been validated in a large number of experimental
      animal models where dys-regulation of the immune system plays a role. Chimeric
      5D12 (ch5D12) was constructed to reduce the potential immunogenicity and enhance
      the in vivo half-life when used in humans. ch5D12 is a molecularly engineered
      human IgG(4) antibody containing the variable domains of the heavy and light
      chains of the murine version of 5D12 (mu5D12). This new chimeric Mab was tested
      in a marmoset experimental autoimmune encephalomyelitis model and was shown to
      effectively prevent disease symptoms. The results of this in vivo evaluation
      supported clinical use of ch5D12 for immune targeted diseases. Therefore GMP
      material was prepared and a GLP-compliant tissue cross-reactivity study on human
      tissues (3 donors/37 tissues) and cynomolgus tissues (2 donors/37 tissues) was
      performed. ch5D12 stained on the surface of B cells and selected dendritic cells
      and no unexpected cross-reactivity was observed. The identical staining patterns
      in human and cynomolgus tissues justified the use of cynomolgus monkeys as a
      relevant model for humans. A GLP-compliant safety and tolerability evaluation for
      ch5D12 in cynomolgus monkeys was performed using the GMP produced material.
      Weekly administration of ch5D12 at two dose levels for 4 weeks was shown to be
      safe and without any side effects in all monkeys.

PMID- 11972993
TI  - Biological basis of visceral pain: recent developments.

PMID- 11972994
TI  - Group differences in pain modulation: pain-free women compared to pain-free men
      and to women with TMD.
AB  - Previously reported differences in sensitivity to experimental pain stimuli
      between the sexes, as well as between temporomandibular disorder (TMD) patients
      and healthy control subjects, may be attributable in part to group differences in
      two pain modulatory mechanisms: the baroreceptor reflex arc and the endogenous
      opioid system. Twenty-two pain-free (PF) men, 20 PF women and 20 women with TMD
      underwent two testing sessions in which heat pain and ischemic arm pain threshold
      and tolerance were measured during both sessions, but followed relaxation during
      one session and laboratory stress tasks during the other. Blood pressure (BP) and
      plasma -endorphin (E) concentration were measured during a baseline rest and
      during the stress or relaxation periods. PF men's threshold and tolerance for
      heat pain, but not for ischemic pain, exceeded that of PF women's during both
      sessions. PF women and TMD women did not differ in sensitivity to either pain
      modality; however, significantly lower ischemic pain threshold (IPTh) was linked
      to oral contraceptive use in PF women but not TMD patients. In the men alone,
      higher baseline systolic BP (SBP) was correlated with higher heat pain threshold
      on both days and heat pain tolerance on the stress day. Conversely, in TMD women,
      higher baseline SBP was correlated with lower ischemic pain tolerance (IPTol) on
      both days; BP and pain sensitivity were not related in PF women. In men, but not
      in PF or TMD women, stress systolic and diastolic BP were positively correlated
      with heat pain threshold and tolerance and higher diastolic reactivity to stress
      were correlated with higher heat pain and IPTh and tolerance. On the stress day,
      higher baseline E level was strongly associated with higher IPTol in PF women but
      marginally associated with lower IPTol in TMD women. Thus, it appears that a BP
      related analgesic mechanism (probably baroreceptor-mediated) predominates in PF
      men, while an endogenous opioid mechanism predominates in PF women. Stress
      enhances the expression of these central mechanisms. Female TMDs appear unable to
      effectively engage normal pain-inhibitory systems; opioid receptor
      desensitization and/or downregulation are probably implicated, because TMDs'
      production of E appears normal.

PMID- 11972995
TI  - Does chronic pain predict future psychological distress?
AB  - Cross-sectional studies have consistently shown a relationship between chronic
      widespread pain, the clinical hallmark of fibromyalgia, and psychological
      distress. These studies cannot distinguish the direction of any causal
      relationship. Recent population based studies have reported that such pain is
      predictive of future distress. However, chronic pain is often associated with
      physical and psychological co-morbid features which may confound this
      relationship. The aim of this study was to examine the hypothesis that chronic
      widespread pain increases the risk of future distress after adjusting for the
      effects of possible confounding factors. A population based survey of 1953
      individuals identified subjects' psychological status and whether they satisfied
      criteria for chronic widespread pain. At baseline co-morbid features of chronic
      widespread pain, including reporting other somatic symptoms, abnormal illness
      behaviour, health anxiety, fatigue and low levels of self-care, were measured.
      All subjects were followed up after 12 months to determine levels of
      psychological distress. Subjects with chronic widespread pain at baseline were
      much more likely to be distressed at follow up (OR=4.0, 95% CI (2.5,6.3)). As
      levels of distress at follow up may simply reflect those at baseline the
      association was adjusted for baseline levels of distress. Chronic widespread pain
      was, however, still associated with future distress although the relationship was
      slightly attenuated (odds ratio, OR=3.0, 95% CI (1.8,5.1)). To examine our main
      hypothesis a final analysis was undertaken adjusting this association for those
      co-morbid features assessed at baseline. Following these adjustments chronic
      widespread pain was no longer significantly associated with future distress
      (OR=1.5, 95% CI (0.8,2.9)). Chronic widespread pain was associated with increased
      levels of psychological distress at follow up. However, a more rigorous analysis
      indicated that the association between baseline pain status with future distress
      was explained by concomitant features of chronic pain rather than pain per se.
      These findings indicate that it is those persons with chronic widespread pain in
      the presence of other physical and psychosocial factors who will become
      distressed.

PMID- 11972996
TI  - Preferential stimulation of Adelta fibers by intra-epidermal needle electrode in
      humans.
AB  - We recorded evoked potentials (EPs) induced by conventional transcutaneous
      electrical stimulation (TS), laser stimulation (LS) and epidermal electrical
      stimulation (ES) using a specially made needle electrode. We evaluated the
      activated fibers by epidermal stimulation by assessing the conduction velocity
      (CV) of the peripheral nerves. The EPs were recorded from Cz electrode (vertex)
      of the International 10-20 system in 12 healthy subjects. For the ES, the tip of
      a stainless steel needle electrode was inserted in the epidermis of the skin (0.2
      mm in depth). Distal and proximal sites of the upper limb were stimulated by the
      LS and ES with an intensity which induced a definite pain sensation. Similar
      sites were stimulated by TS with an intensity of two times the sensory threshold.
      A major EP positive response (P1) was obtained by stimulation by all three types
      of stimuli. The P1 latency for the TS (245+/-22 ms) was significantly shorter
      than that for the ES (302+/-17 ms, P<0.0001) and LS (341+/-21 ms, P<0.0001) and
      the peak latency P1 by the LS was also significantly longer, approximately 40 ms,
      than that by the ES (P<0.0001). The CVs were 15.1, 15.3 and 44.1 m/s obtained by
      ES, LS and TS, respectively. The CV indicated that the fibers activated by the ES
      were mainly A fibers, which corresponded to the fibers stimulated by the LS. We
      considered that the ES with our newly developed needle electrode was a very
      convenient method for the selective stimulation of the A fibers, since it was
      very simple, not requiring any special apparatus, did not cause bleeding or burns
      and caused minimum uncomfortable feeling.

PMID- 11972997
TI  - CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain.
AB  - The cannabinoid agonist, HU210 has been evaluated in vivo in nociceptive and
      inflammatory pain models in the rat. The ED50 for the anti-nociceptive
      (increasing mechanical withdrawal threshold) effect was 0.1 mg/kg-1 i.p., and for
      anti-hypersensitivity and anti-inflammatory activity was 5 g/kg-1 i.p. (in the
      carrageenan model). The selective CB1 antagonist, AM281 (0.5 microg/kg-1 i.p.)
      reversed effects of HU210 (10 and 30 microg/kg-1 i.p.) in both nociceptive and
      inflammatory models of hypersensitivity. The selective CB2 antagonist, SR144528
      (1 mg/kg-1 i.p.) antagonised effects of HU210 (30 microg/kg-1 i.p.) in the
      carrageenan induced inflammatory hypersensitivity. The CB2 agonist, 1-(2,3
      Dichlorobenzoyl)-5-methoxy-2-methyl-(2-(morpholin-4-yl)ethyl)-1H-indole
      (GW405833) inhibited the hypersensitivity and was anti-inflammatory in vivo.
      These effects were blocked by SR144528. These findings suggest that CB1 receptors
      are involved in nociceptive pain and that both CB1 and CB2 receptors are involved
      in inflammatory hypersensitivity. Future studies will investigate effects on
      identified inflammatory cells within the inflamed tissue to further elucidate the
      role of cannabinoid receptors.

PMID- 11972998
TI  - Analgesic effects of dextromethorphan and morphine in patients with chronic pain.
AB  - N-methyl-aspartate (NMDA) receptor antagonists have been shown to improve opioid
      analgesia in the animal model. The cough suppressant dextromethorphan is a
      clinically available NMDA-receptor antagonist. In this randomised, double-blind,
      placebo-controlled study 20 patients with chronic pain of several years duration
      were given 100 mg of oral dextromethorphan or matching placebo 4 h prior to an
      intravenous infusion of morphine 15 mg. Pain intensity and adverse effects were
      assessed at 0, 4, 5 and 7 h. Dextromethorphan had no effect on morphine
      analgesia: the mean (+/-SEM) visual analogue scores for pain relief (VAS, 0-100
      mm) at the end of the morphine infusion were 38 (+/-6) for
      dextromethorphan+morphine and 38 (+/-7) for placebo+morphine. VAS scores for pain
      intensity were comparable both at rest and at movement at all time points. The
      most common adverse effects reported were dizziness, nausea and sedation. There
      were no significant differences in either the incidence or severity of adverse
      effects. In conclusion, oral dextromethorphan 100 mg had no effect on pain relief
      by intravenous morphine 15 mg in patients with chronic pain.

PMID- 11972999
TI  - The pattern of expression of the voltage-gated sodium channels Na(v)1.8 and
      Na(v)1.9 does not change in uninjured primary sensory neurons in experimental
      neuropathic pain models.
AB  - A spared nerve injury of the sciatic nerve (SNI) or a segmental lesion of the L5
      and L6 spinal nerves (SNL) lead to behavioral signs of neuropathic pain in the
      territory innervated by adjacent uninjured nerve fibers, while a chronic
      constriction injury (CCI) results in pain sensitivity in the affected area. While
      alterations in voltage-gated sodium channels (VGSCs) have been shown to
      contribute to the generation of ectopic activity in the injured neurons, little
      is known about changes in VGSCs in the neighboring intact dorsal root ganglion
      (DRG) neurons, even though these cells begin to fire spontaneously. We have now
      investigated changes in the expression of the TTX-resistant VGSCs, Nav1.8
      (SNS/PN3) and Nav1.9 (SNS2/NaN) by immunohistochemistry in rat models of
      neuropathic pain both with an intermingling of intact and degenerated axons in
      the nerve stump (SNL and CCI) and with a co-mingling in the same DRG of neurons
      with injured and uninjured axons (sciatic axotomy and SNI). The expression of
      Nav1.8 and Nav1.9 protein was abolished in all injured DRG neurons, in all
      models. In intact DRGs and in neighboring non-injured neurons, the expression and
      the distribution among the A- and C-fiber neuronal populations of Nav1.8 and
      Nav1.9 was, however, unchanged. While it is unlikely, therefore, that a change in
      the expression of TTX-resistant VGSCs in non-injured neurons contributes to
      neuropathic pain, it is essential that molecular alterations in both injured and
      non-injured neurons in neuropathic pain models are investigated.

PMID- 11973000
TI  - The relationship of pain and depression to cognitive function in rheumatoid
      arthritis patients.
AB  - The purpose of this study was to assess the hypothesis that pain and depression
      negatively impact the cognitive functioning of individuals with rheumatoid
      arthritis (RA). One hundred twenty-one community-dwelling RA patients (ages 34
      84) completed a battery of cognitive tasks and multiple measures of pain and
      depression. Structural equation modeling techniques were used to assess the
      relative contributions of pain, depression, and age to cognitive performance.
      Individuals who performed poorly on cognitive tasks reported more pain and
      depression and were older than those individuals who performed well on cognitive
      tasks. Moreover, high levels of pain were associated with depression. Further
      analyses revealed that depression mediated the relationship between pain and
      cognition. That is, when depression was entered into the analyses, the previously
      significant effects of pain on cognition were no longer found. Interestingly,
      depression still mediated the pain-cognition relationship even after controlling
      for age. These findings suggest the importance of both pain and depression for
      understanding cognitive function in RA and may have important implications for
      treating this disease.

PMID- 11973001
TI  - Twenty-four hour exposure to prostaglandin downregulates prostanoid receptor
      binding but does not alter PGE(2)-mediated sensitization of rat sensory neurons.
AB  - Although the tissue levels of prostaglandins are elevated for a relatively long
      period during injury or inflammation, few studies have been performed to assess
      the effects of prolonged prostaglandin exposure on receptor binding and activity
      in sensory neurons. Consequently, we examined whether unilateral inflammation or
      a 24 h exposure to prostaglandin E2 (PGE2) altered binding of this prostanoid in
      spinal cord tissue or in isolated sensory neurons, respectively. To assess
      functional changes in EP receptors, we also examined PGE2-induced cAMP production
      and the prostanoid-mediated augmentation of substance P release from isolated
      sensory neurons after acute and 24 h pretreatment with PGE2. Injection of
      complete Freund's adjuvant into the hindpaw decreased binding of PGE2 in
      ipsilateral, but not contralateral dorsal spinal cord 24 h after injection. This
      decrease in Bmax was blocked by administration of intrathecal ketorolac (10
      nmol/microl/h) for 24 h prior to and throughout the period of inflammation,
      suggesting that the inflammation-induced decrease in binding is dependent on
      prostaglandin synthesis. In an analogous manner, treating sensory neurons grown
      in culture with 1 microM PGE2 for 24 h decreased [3H]-PGE2 binding by
      approximately 50% without altering binding affinity. Exposing neuronal cultures
      to 1 microM PGE2 for 24 h also reduced, but did not abolish the ability of the
      prostanoid to increase the production of cAMP. This treatment, however, did not
      significantly alter the ability of PGE2 to augment the evoked release of
      immunoreactive substance P from sensory neurons. These results demonstrate that
      under conditions that significantly downregulate PGE2 binding, sensory neurons
      are still capable of maintaining PGE2-mediated sensitization.

PMID- 11973002
TI  - The roles of pathways in the spinal cord lateral and dorsal funiculi in signaling
      nociceptive somatic and visceral stimuli in rats.
AB  - The spinothalamic tract (STT) is a major ascending nociceptive pathway,
      interruption of which by cordotomy is used for pain relief, whereas the dorsal
      column (DC) pathway is usually not considered to be involved in pain
      transmission. However, recent clinical studies showed good relief of visceral
      pain in cancer patients after a DC lesion. Electrophysiological recordings in
      animals suggest that the analgesic effect is due to interruption of axons
      ascending from postsynaptic dorsal column (PSDC) neurons located in the vicinity
      of the central canal. In this behavioral study, we used a decrease in exploratory
      activity in rats after a noxious stimulus as an indicator of perceived pain,
      independent of withdrawal reflexes. Intradermal capsaicin injection almost
      abolished exploratory activity in naive animals or in rats after a DC lesion, but
      did not change it in rats after ipsilateral dorsal rhizotomy or a lesion of the
      lateral funiculus on the side opposite to the injection. In contrast, a bilateral
      DC lesion counteracted the decrease in exploratory activity induced by noxious
      visceral stimuli for at least 180 days after the surgery. Although neurons
      projecting in both the STT and the PSDC path can be activated by noxious stimuli
      of cutaneous or visceral origin, our results suggest that the STT plays a crucial
      role in the perception of acute cutaneous pain and that the DC pathway is
      important for transmission of visceral pain.

PMID- 11973003
TI  - Activation of spinal ORL-1 receptors prevents acute cutaneous neurogenic
      inflammation: role of nociceptin-induced suppression of primary afferent
      depolarization.
AB  - Neurogenic inflammation is an inflammatory response of peripheral tissue to
      vasoactive substances released from sensory afferent terminals. It can be
      triggered via a local axon reflex and by dorsal root reflex (DRR) activity
      involving the spinal cord. Nociceptin, an endogenous ligand for the opioid
      receptor-like (ORL-1) G-protein coupled receptor, has been found to inhibit the
      local axon reflex-mediated neurogenic inflammation by suppressing the release of
      vasoactive neuropeptides from sensory afferent terminals. The present study was
      to explore the role of spinal ORL-1 receptors in the modulation of DRR-induced
      neurogenic inflammation. We first examined the effect of nociceptin on DRR by
      recording dorsal root potentials (DRPs) and the associated antidromic discharges,
      evoked by electrical stimulation of an adjacent dorsal root in an in vitro
      neonatal rat spinal cord preparation. Nociceptin reversibly inhibited the DRP in
      a concentration-dependent manner (IC50: approximately 45 nM, maximal inhibition:
      approximately 50%), an effect that was antagonized by the ORL-1 receptor
      antagonist, J-113397. Neurochemical studies demonstrated that nociceptin (10
      microM) also produced an approximately 40% reduction in gamma amino butyric acid
      (GABA) release evoked by electrical stimulation of neonatal rat spinal cord
      slices. On the other hand, nociceptin had no effect on exogenous GABA-evoked DRP.
      These findings suggest that the nociceptin-induced inhibition of the DRP is most
      likely due to the suppression of GABA release, the principle transmitter
      mediating DRP, from GABAergic neurons that are pre-synaptic to primary afferent
      terminals. Finally, in order to explore the physiological significance of such
      modulation in a fully integrated system, we evaluated the effect of intrathecally
      administered nociceptin on capsaicin-induced acute cutaneous neurogenic
      inflammation in rat hind paw, quantified by examining the degree of paw edema in
      anesthetized rats. The magnitude of capsaicin-induced increase of paw thickness
      was reduced by approximately 50% from 31+/-1.34% (n=6) to 15+/-1.63% (n=8;
      P<0.05) by nociceptin (10 micromol). We conclude that spinal ORL-1 receptors can
      modulate neurogenic inflammation by suppressing the GABAergic neuronal activity
      in the dorsal horn that is responsible for generating DRRs.

PMID- 11973004
TI  - A confirmatory factor analysis of the Pain Catastrophizing Scale: invariant
      factor structure across clinical and non-clinical populations.
AB  - This study examined the factor structure of the Pain Catastrophizing Scale in
      three different Dutch-speaking samples: 550 pain-free students, 162 chronic low
      back pain patients, and 100 fibromyalgia patients. Confirmatory factor analyses
      were used to compare three different models of pain catastrophizing (one factor,
      two oblique factors, three oblique factors), and to investigate the invariance of
      the factor structure across the three different samples. The results indicated
      that a three-factor oblique model with a four-item rumination factor, a three
      item magnification factor, and a six-item helplessness factor provided the best
      fit to the data in the three samples. Furthermore, it was found that this model
      could be considered as invariant across three samples (pain-free students,
      chronic low back pain patients, and fibromyalgia patients) and across gender,
      indicating that the same processes are measured in different subgroups.

PMID- 11973005
TI  - Pitfalls of opioid rotation: substituting another opioid for methadone in
      patients with cancer pain.
AB  - The successful use of methadone in cancer pain has been supported by numerous
      case reports and clinical studies. Methadone is usually used as a second or third
      line opioid medication. As the use of methadone increases we are facing the
      challenge of converting methadone to other opioids as part of sequential opioid
      trials. Data on the equianalgesic ratios for the substitution of other opioids
      for methadone are lacking. We present prospective data on 13 consecutive
      rotations from methadone to a different opioid. The opioid rotation was followed
      by escalation of pain and/or severe dysphoria, not controlled by a rapid increase
      in the dose of the second opioid, in 12 of the 13 patients. Only one patient was
      successfully maintained on the second opioid after the discontinuation of
      methadone, while 12 patients required a switch back to methadone. We conclude
      that opioid rotation from methadone to another opioid is often complicated by
      worsening pain and dysphoria. These symptoms may not improve despite upward
      titration of the second opioid. A uniformly accepted conversion ratio for
      substituting methadone with another opioid is currently not available. More data
      on the rotation from methadone to other opioids are needed.

PMID- 11973006
TI  - Case reports - reversal of sensory deficit associated with pain relief after
      treatment with gabapentin.
AB  - Many patients with neuropathic pain have coexistent sensory deficits. Neuropathic
      pain may be alleviated by a variety of drugs but sensory deficits are assumed to
      be permanent. In an audit of the effects of gabapentin therapy on patients with
      neuropathic pain, monthly detailed sensory examinations were performed during the
      first three months of treatment. Of five patients with sensory deficits who
      tolerated gabapentin therapy, three showed marked improvement of their sensory
      deficits associated with pain alleviation. The cases are presented and possible
      explanations for the observed sensory improvements are discussed. These findings
      raised exciting neurophysiological questions in addition to being of potential
      importance to the clinical problem of neurotrophic tissue injury.

PMID- 11973007
TI  - Gender role expectations of pain: relationship to experimental pain perception.
AB  - The primary purpose of this study was to investigate the influence of an
      individual's Gender Role Expectations of Pain (GREP) on experimental pain report.
      One hundred and forty-eight subjects (87 females and 61 males) subjects underwent
      thermal testing and were asked to report pain threshold, pain tolerance, VAS
      ratings of pain intensity and unpleasantness, and a computerized visual analogue
      scales (VAS) rating of pain intensity during the procedure. Subjects completed
      the GREP questionnaire to assess sex-related stereotypic attributions of pain
      sensitivity, pain endurance, and willingness to report pain. Consistent with
      previous research, significant sex differences emerged for measures of pain
      threshold, pain tolerance, and pain unpleasantness. After statistically
      controlling for age, GREP scores were significant predictors of threshold,
      tolerance, and pain unpleasantness, accounting for an additional 7, 11, and 21%
      of the variance, respectively. Sex remained a significant predictor of pain
      tolerance in hierarchical regression analyses after controlling for GREP scores.
      Results provide support for two competing but not mutually exclusive hypotheses
      related to the sex differences in experimental pain. Both psychosocial factors
      and first-order, biological sex differences remain as viable explanations for
      differences in experimental pain report between the sexes. It appears that GREP
      do play a part in determining an individual's pain report and may be contributing
      to the sex differences in the laboratory setting.

PMID- 11973008
TI  - Epidural spinal cord stimulation for the treatment of painful legs and moving
      toes syndrome.
AB  - A case of 51-year-old male with painful legs and moving toes syndrome was
      successfully treated with epidural spinal cord stimulation. He was previously
      treated with varieties of medication, epidural block, transcutaneous nerve
      stimulation, lumbar sympathetic block, with no or only a transient effect.
      Epidural spinal cord stimulation was applied by means of percutaneously inserted
      epidural electrodes connected to a percutaneous extension for 2-week test
      stimulation period and later to a permanent device (ITREL). Pain and involuntary
      movement were relieved almost completely during the stimulation and the effect
      was still evident 6 months later.

PMID- 11973009
TI  - A prospective study of the effects of sexual or physical abuse on back pain.
AB  - A prospective investigation of the effects of abuse on future pain and disability
      was conducted in order to understand better the possible causal role of abuse.
      Participants were 422 females from a previous population study (Pain 73 (1997) 47
      53) who either reported no spinal pain (n=194) or some spinal pain (n=228) at the
      baseline. A standardized questionnaire was used to assess self-reported physical
      and sexual abuse during childhood and as an adult. One year later, a follow-up
      questionnaire was used to evaluate pain and physical function outcomes. Results
      for the No Pain Group showed that only self-reported physical abuse at baseline
      was associated with an increased occurrence of new episodes of back pain (odds
      RATIO=2.65). Both sexual and physical abuse were linked to as much as four-fold
      increase in the occurrence of a new episode of functional problems at follow-up.
      However, for the Pain Group, no significant differences were found between those
      reporting and not reporting abuse at baseline and either pain or disability at
      follow-up. This unique prospective study with individuals from the general
      population underscores the probable importance of abuse in the etiology of a pain
      or disability problem. Nevertheless, since no clear relationship between abuse
      and pain was shown for those already reporting pain at baseline, the role of
      abuse in the development of persistent pain is still not comprehensible. There is
      a need for investigations with prospective designs employing patients as well as
      nonpatients as subject.

PMID- 11973010
TI  - Antihyperalgesic effects of intrathecal neuropeptide Y during inflammation are
      mediated by Y1 receptors.
AB  - Inflammation induces an up-regulation of neuropeptide tyrosine (NPY) and its
      receptors in the dorsal horn, suggesting an important role in nociceptive
      transmission. Our initial studies revealed that NPY dose-dependently increased
      hotplate response latency, and to a lesser degree, thermal paw withdrawal latency
      (PWL); these effects occurred at doses that affect neither motor coordination (as
      assessed by the rotarod test) nor paw skin temperature. We next evaluated the
      behavioral effects of intrathecal administration of NPY and NPY antagonists with
      the aim of assessing the contribution of NPY to correlates of persistent
      nociception associated with the unilateral plantar injection of carrageenan or
      complete Freund's adjuvant (CFA). NPY robustly and dose-dependently increased PWL
      on the side ipsilateral to carrageenan injection, with only a small effect on the
      contralateral side. Similarly, NPY (30 microg) produced a large and long-lasting
      increase in PWL on the side ipsilateral to CFA injection (140% change), with only
      a small effect on the contralateral side (25% change). The ipsilateral effect of
      NPY was completely inhibited with the potent Y1 antagonist, BIBO 3304 (3 microg),
      but not the Y2 antagonist, BIIE 0246. When administered alone, BIBO 3304 (but not
      BIIE 0246) slightly decreased thermal PWL on the side ipsilateral (25% change),
      but not contralateral, to CFA injection; this suggests that inflammation
      strengthens inhibitory NPY tone. We conclude that spinal Y1 receptors contribute
      to the inhibitory effects of NPY on thermal hypersensitivity in the awake rat.
      Further studies are necessary to determine whether enhanced release of NPY and Y1
      mediated inhibition of spinal nociceptive transmission ultimately results in a
      compensatory, adaptive inhibition of thermal hypersensitivity in the setting of
      inflammation.

PMID- 11973011
TI  - Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a
      randomized controlled trial.
AB  - Chronic pain in persons with spinal cord injury (SCI) is a difficult problem for
      which there is no simple method of treatment. Few randomized controlled trials of
      medications for pain in persons with SCI have been conducted. This study was
      designed to determine whether amitriptyline, a tricyclic antidepressant, is
      efficacious in relieving chronic pain and improving pain-related physical and
      psychosocial dysfunction in persons with SCI. Eighty-four participants with SCI
      and chronic pain were randomized to a 6-week trial of amitriptyline or an active
      placebo, benztropine mesylate. All pre- and post-treatment assessments were
      conducted by evaluators blind to the allocation. Regression analyses were
      conducted to examine whether there was a medication group effect on the primary
      (average pain intensity) and secondary outcome measures. No significant
      differences were found between the groups in pain intensity or pain-related
      disability post-treatment, in either intent-to-treat analyses or analyses of
      study completers. These findings do not support the use of amitriptyline in the
      treatment of chronic pain in this population, but we cannot rule out the
      possibility that certain subgroups may benefit.

PMID- 11973012
TI  - Lamotrigine in spinal cord injury pain: a randomized controlled trial.
AB  - The objective was to investigate the effectiveness of lamotrigine for the
      treatment of spinal cord injury pain and clinical signs of neuronal
      hyperexcitability. Thirty patients with spinal cord injury (SCI) and at or below
      level neuropathic pain participated in a randomized double blind, placebo
      controlled, crossover trial. A 1-week baseline period was followed by two
      treatment periods of 9 weeks duration with lamotrigine slowly increased to a
      maximum of 400 mg or placebo separated by a 2-week washout period. The primary
      outcome measure was the change in median pain score from baseline week to the
      last week of treatment. Secondary outcome measures included thresholds to
      standardized sensory stimuli using quantitative sensory testing. Twenty-two
      patients completed the trial. We found no statistically significant effect of
      lamotrigine as evaluated in the total sample. However, in patients with
      incomplete SCI, lamotrigine significantly reduced pain at or below SCI level.
      Patients with brush evoked allodynia and wind-up-like pain in the area of maximal
      pain were more likely to have a positive effect to lamotrigine than patients
      without these evoked pains (7 of 7 vs. 1 of 14). Lamotrigine was generally well
      tolerated. While this trial showed no significant effect on spontaneous and
      evoked pain in complete and incomplete spinal cord injury, lamotrigine reduced
      spontaneous pain in patients with incomplete spinal cord injury and evoked pain
      in the area of spontaneous pain.

PMID- 11973013
TI  - Identification of quantitative trait loci for chemical/inflammatory nociception
      in mice.
AB  - Sensitivity to pain is widely variable, and much of this variability is genetic
      in origin. The specific genes responsible have begun to be identified, but only
      for thermal nociception. In order to facilitate the identification of
      polymorphic, pain-related genes with more clinical relevance, we performed
      quantitative trait locus (QTL) mapping studies of the most common assay of
      inflammatory nociception, the formalin test. QTL mapping is a technique that
      exploits naturally occurring variability among inbred strains for the
      identification of genomic locations containing genes contributing to that
      variability. An F2 intercross was constructed using inbred A/J and C57BL/6J mice
      as progenitors, strains previously shown to display resistance and sensitivity,
      respectively, to formalin-induced nociception. Following phenotypic testing (5%
      formalin, 25 microl intraplantar injection), mice were genotyped at 90
      microsatellite markers spanning the genome. We provide evidence for two
      statistically significant formalin test QTLs - chromosomal regions whose
      inheritance is associated with trait variability - on distal mouse chromosomes 9
      and 10. Identification of the genes underlying these QTLs may illuminate the
      basis of individual differences in inflammatory pain, and lead to novel analgesic
      treatment strategies.

PMID- 11973014
TI  - The contribution of suggestibility and expectation to placebo analgesia
      phenomenon in an experimental setting.
AB  - This study reports how placebo analgesia was produced by conditioning whereby the
      intensity of electric stimulation was surreptitiously reduced in order to examine
      the contribution of psychological factors of suggestibility and expectancy on
      placebo analgesia. This strategy was used in order to manipulate expectancy for
      pain reduction. The magnitudes of the placebo effects were estimated after a
      manipulation procedure and during experimental trials in which stimulus
      intensities were reset to original baseline levels. Individual differences in
      suggestibility, verbal expectancy for drug efficacy and manipulation procedure
      for pain reduction were tested as possible mediators of placebo analgesia. The
      following dependent variables were measured: (a) subjective expectancy for drug
      efficacy in pain relief, (b) expected pain intensity and unpleasantness, (c)
      concurrent pain intensity and unpleasantness and (d) remembered pain intensity
      and unpleasantness. Statistically significant placebo effects on sensory and
      affective measures of pain were obtained independently of the extent of the
      surreptitious lowering of stimulus strength during manipulation trials. The
      pairing of placebo administration with painful stimulation was sufficient to
      produce a generalized placebo analgesic effect. However, verbal expectancy for
      drug efficacy and individual differences in suggestibility were found to
      contribute significantly to the magnitude of placebo analgesia. The highest
      placebo effect was shown by the most pronounced reductions in pain ratings in
      highly suggestible subjects who received suggestions presumed to elicit high
      expectancy for drug efficacy. The results also demonstrated that placebo effects
      established on remembered pain were at least twice as great as those obtained on
      concurrent placebo effects. This was mainly because baseline pain was remembered
      as being much more intense than it really was. Moreover, remembered placebo
      effects, like the concurrent placebo effects, were highly correlated with
      expected pain scores obtained just after manipulation trials. These results
      indicate that multiple factors contribute to the placebo effect, including
      suggestibility, expectancy and conditioning, and that the judgement of placebo
      analgesia is critically determined by whether pain relief is assessed
      concurrently or after treatment.

PMID- 11973017
TI  - Clarifying the definition of neuropathic pain.

PMID- 11973015
TI  - Spiritual healing as a therapy for chronic pain: a randomized, clinical trial.

PMID- 11973019
TI  - Clarifying definition of neuropathic pain.

PMID- 11973020
TI  - Re: Silas Weir Mitchell: a typographical mischance.

PMID- 11973021
TI  - Comment on Rice ASC, Maton S, the Postherpetic Neuralgia Study Group (UK),
      gabapentin in postherpetic neuralgia: a randomized, double blind, placebo
      controlled study.

PMID- 11973022
TI  - Comment on Rice ASC, Maton S, the Postherpetic Neuralgia Study Group (UK),
      gabapentin in postherpetic neuralgia: a randomized, double blind, placebo
      controlled study.

PMID- 11973024
TI  - Functional magnetic resonance imaging of the human cervical spinal cord with
      stimulation of different sensory dermatomes.
AB  - Functional MR imaging (fMRI) of the cervical spinal cord was carried out in 13
      healthy volunteers. A cold stimulus was applied, at different times, to three
      different sensory dermatome regions overlying the right hand and forearm: the
      thumb side of the palm, the little finger side of the palm, and the forearm below
      the elbow. Stimulation of these areas is expected to involve the 6(th), 8(th),
      and 5(th) cervical spinal cord segments respectively. Whereas true activations
      are expected to correspond to the region being stimulated, false activations such
      as arising from noise and motion, are not. The results demonstrate that
      clustering of active pixels into groups based on their intensity time courses
      discriminates false activations from true activations. Following clustering, the
      distribution of activity observed with fMRI matched the expected regions of
      neuronal activation with the different areas of stimulation on the hand and
      forearm.

PMID- 11973025
TI  - Characterization of BOLD-fMRI signal during a verbal fluency paradigm in patients
      with intracerebral tumors affecting the frontal lobe.
AB  - Previous studies have indicated that the BOLD-fMRI signal can be modified by
      tumor processes in close vicinity to functional brain areas. This effect has been
      investigated primarily for the perirolandic area but there is only a limited
      number of studies concerning frontal cortical regions. Therefore, the aim of the
      current study was to characterize BOLD-fMRI signal and activation patterns in
      patients with frontal brain tumors while performing a verbal fluency task. Six
      patients (ages 31-56 years) suffering from frontal (5 left sided and 1 right
      sided) intracerebral tumors were examined with fMRI while performing a verbal
      fluency task in a blocked paradigm design. Eight healthy volunteers served as the
      control group. The patients (5 right and 1 left handed) demonstrated left frontal
      activation which could be clearly located outside the tumor area and adjacent
      edema with varying degrees of additional right frontal activation. In the
      predominant left frontal activation cluster, the mean voxel based z-score and
      cluster size were not statistically different between patients and controls. The
      present fMRI study is indicating that language related BOLD signal changes in the
      frontal cortex of patients with tumors close to functional areas were comparable
      to the signal in normal controls. Additionally, the temporal hemodynamic response
      characteristic was comparable in both groups. This is an important finding
      consistent with PET results and corroborates the feasibility of functional
      mapping approaches in patients with tumors affecting the frontal lobe. Additional
      studies investigating alterations of the hemodynamic response depending on tumor
      location and histology are required in order to further elucidate the association
      between pathophysiology and BOLD fMRI signal.

PMID- 11973026
TI  - Improved detection of time windows of brain responses in fMRI using modified
      temporal clustering analysis.
AB  - Temporal clustering analysis (TCA) has been proposed recently as a method to
      detect time windows of brain responses in functional MRI (fMRI) studies when the
      timing and location of the activation are completely unknown. Modifications to
      the TCA technique are introduced in this report to further improve the
      sensitivity in detecting brain activation. The modified TCA is based on the
      integrated signal intensity of a temporal cluster at each time point, while the
      original TCA is based only on the size of a temporal cluster at each time point.
      A temporal cluster at each time point is defined, in both TCA methods, as a group
      of pixels reaching their maximum (or minimum) values at the same time. Both
      computer simulation and in vivo fMRI experiments have been performed. Compared
      with the original TCA, the modified TCA shows a significant improvement in the
      sensitivity to detect activation peaks for determining time windows of brain
      responses.

PMID- 11973027
TI  - MR image-based measurement of rates of change in volumes of brain structures.
      Part I: method and validation.
AB  - A detailed analysis procedure is described for evaluating rates of volumetric
      change in brain structures based on structural magnetic resonance (MR) images. In
      this procedure, a series of image processing tools have been employed to address
      the problems encountered in measuring rates of change based on structural MR
      images. These tools include an algorithm for intensity non-uniformity correction,
      a robust algorithm for three-dimensional image registration with sub-voxel
      precision and an algorithm for brain tissue segmentation. However, a unique
      feature in the procedure is the use of a fractional volume model that has been
      developed to provide a quantitative measure for the partial volume effect. With
      this model, the fractional constituent tissue volumes are evaluated for voxels at
      the tissue boundary that manifest partial volume effect, thus allowing tissue
      boundaries be defined at a sub-voxel level and in an automated fashion.
      Validation studies are presented on key algorithms including segmentation and
      registration. An overall assessment of the method is provided through the
      evaluation of the rates of brain atrophy in a group of normal elderly subjects
      for which the rate of brain atrophy due to normal aging is predictably small. An
      application of the method is given in Part II where the rates of brain atrophy in
      various brain regions are studied in relation to normal aging and Alzheimer's
      disease.

PMID- 11973028
TI  - MR image-based measurement of rates of change in volumes of brain structures.
      Part II: application to a study of Alzheimer's disease and normal aging.
AB  - We present global and regional rates of brain atrophy measured on serially
      acquired T1-weighted brain MR images for a group of Alzheimer's disease (AD)
      patients and age-matched normal control (NC) subjects using the analysis
      procedure described in Part I. Three rates of brain atrophy: the rate of atrophy
      in the cerebrum, the rate of lateral ventricular enlargement and the rate of
      atrophy in the region of temporal lobes, were evaluated for 14 AD patients and 14
      age-matched NC subjects. All three rates showed significant differences between
      the two groups. However, the greatest separation of the two groups was obtained
      when the regional rates were combined. This application has demonstrated that
      rates of brain atrophy, especially in specific regions of the brain, based on MR
      images can provide sensitive measures for evaluating the progression of AD. These
      measures will be useful for the evaluation of therapeutic effects of novel
      therapies for AD.

PMID- 11973029
TI  - Separation of arteries and veins using flow-induced phase effects in contrast
      enhanced MRA of the lower extremities.
AB  - In 3-D contrast-enhanced magnetic resonance (MR) angiography of the lower
      extremities the goal is most often to enhance arterial structures while keeping
      veins and surrounding tissue unenhanced. Imaging during steady-state
      concentration of a blood pool agent or during poor timing of an extra-cellular
      contrast medium may result in simultaneous venous enhancement, making
      interpretation of the angiogram difficult. The aim of this study was to develop a
      post-processing method to separate the arteries from the veins in standard
      contrast-enhanced MR angiograms. The method was based on the different
      accumulation of flow-induced phase in the arteries and veins of the lower
      extremities. The method was tested in both phantom experiments and volunteers
      undergoing 3-D contrast-enhanced MR angiography using both an extra-cellular
      contrast medium and a blood pool agent. In the phantom studies, opposite
      directional flow was successfully separated at mean flow velocities as low as 9
      cm/s. In the volunteer studies, the larger veins were successfully extinguished
      while the larger arteries were left unaffected. In smaller vessels with low flow
      velocities the separation was less successful. This was most apparent in vessels
      not oriented superior-inferior. The method developed here is promising for
      separating arteries from veins in contrast-enhanced MR angiography although the
      results could be further improved by either a different pulse sequence design or
      combining this method with other segmentation methods.

PMID- 11973030
TI  - Diagnosis of discoid lateral meniscus of the knee on MR imaging.
AB  - To establish the quantitative MR diagnostic criteria for discoid lateral
      meniscus, MR imaging of 60 knees with arthroscopically confirmed discoid lateral
      menisci and 134 knees with semilunar lateral menisci were analyzed. Following
      four quantitative parameters were measured. (1) Meniscal width (MW): The minimum
      meniscal width on the coronal slice. (2) Ratio of the meniscus to the tibia
      (RMT): The ratio of minimum meniscal width to maximum tibial width on the coronal
      slice. (3) Percent coverage of the meniscus (PCM): The ratio of the sum of the
      width of the anterior and posterior horns to the meniscal diameter on the
      sagittal slice showing the maximum meniscal diameter. (4) Continuity of the
      anterior and posterior horns (CAPH): The number of consecutive sagittal slices
      showing continuity between the anterior and posterior horns of the meniscus on
      the sagittal slice. The cut-off values of each parameter to discriminate between
      the discoid and semilunar meniscus were calculated based on a univariate logistic
      regression analysis. The sensitivity and specificity were also calculated for
      each of 4 parameters and combinations of these parameters. The cut-off value was
      15 mm for the MW, 20% for the RMT, 75% for the PCM, and 3 slices for the CAPH.
      The sensitivity and specificity of the four parameters ranged between 87% and 50%
      and between 99% and 92%, respectively. The most accurate diagnostic criterion was
      either the RMT > or = 20% or the PCM > or = 75%, and the sensitivity and
      specificity were 95% and 97%, respectively, even when torn menisci were included.

PMID- 11973031
TI  - Estimation of heat transfer and temperature rise in partial-body regions during
      MR procedures: an analytical approach with respect to safety considerations.
AB  - In order to assess thermal response to RF exposure during MR procedures at the
      tissue level, simple analytical solutions to the non-stationary Pennes' bio-heat
      equation were obtained using the Green's function approach. Two thermal models
      appropriate for partial-body exposure were analyzed: In the first model, the
      temperature field at the periphery of an idealized volume RF resonator was
      modeled. The analytical solution reveals that tissue response to RF heating is
      characterized by an equilibration time and length. Both parameters are inversely
      related to tissue perfusion and vary for the soft-tissues considered between 0.27
      25 min and 1.5-12 mm, respectively. None of the tissues investigated increase in
      temperature more than 0.5 degrees C for each W/kg of power dissipated. Secondly,
      a homogeneous tissue solution was derived that predicts the temperature-time
      course to an MR examination with time-varying specific absorption rates (SAR).
      Since SAR limits indicated in current MR safety standards relate to running SAR
      averages computed over an appropriate period of time, an expression was
      formulated that gives an upper limit for the temperature rise averaged over the
      same period of time, as a function of both the upper limit of running SAR
      averages and the duration of the MR examination. The analysis revealed that the
      partial-body SAR limits indicated in the IEC standard may not guarantee under all
      circumstances compliance with the basic restrictions concerning temperature rise.

PMID- 11973032
TI  - In vivo temporal EPR imaging for estimating the kinetics of a nitroxide radical
      in the renal parenchyma and pelvis in rats.
AB  - The kinetics of a nitroxide radical in the renal parenchyma and pelvis in rats
      were investigated by employing an in vivo EPR imaging system equipped with a
      surface-coil-type resonator (SCR). The exposed kidney of a living rat was
      inserted into the single-turn coil of the SCR, with the renal major axis aligned
      with the direction of alternative magnetic field (B(1)). After the injection of
      nitroxide radical via the tail vein, EPR measurements were repeated. From the
      temporal EPR images of the kidney on the 2-D projection to the plane which is
      perpendicular to the direction of B(1,) the decay rate of nitroxide radical in
      the renal parenchyma and pelvis was estimated. The parenchymal decay rate was
      found to be significantly shorter than that for the pelvis.

PMID- 11973033
TI  - The interpretation of multi-exponential water proton transverse relaxation in the
      human and porcine eye lens.
AB  - We report results of 1H NMR transverse relaxation experiments on human and
      porcine eye lenses. Several authors have reported that transverse relaxation is
      not mono-exponential when observed by the Carr-Purcell-Meiboom-Gill (CPMG)
      sequence and have interpreted the results by postulating the presence of "pools"
      of water molecules in different binding environments that do not exchange rapidly
      on the NMR timescale. We have compared CPMG data for intact lenses with results
      for lens homogenates and have combined a CPMG spectroscopic pulse train with NMR
      micro-imaging to study the nature of the transverse relaxation process in human
      and porcine lenses. Fast exchange of water protons with the lens proteins
      (crystallins) leads to an enhanced transverse relaxation rate that varies
      linearly with protein concentration. At the resolution of NMR micro-imaging the
      transverse relaxation process is mono-exponential. The results show that the
      multi-exponential CPMG data observed spectroscopically for whole lenses reflect
      spatial variations in crystallin content through the lens rather than the
      presence of distinct "bound" and "free" water pools.

PMID- 11973034
TI  - Analysis of wave patterns in MR elastography of skeletal muscle using coupled
      harmonic oscillator simulations.
AB  - The ability to study muscle elasticity in vivo would be of great clinical
      interest. Magnetic resonance elastography (MRE) has the potential to quantify
      noninvasively the distribution of the shear modulus in muscle tissue. Elasticity
      information may be derived by extracting frequencies from the wave patterns of
      phase-contrast MRE images. In a new approach, MRE wave patterns were
      reconstructed using 3D coupled harmonic oscillator calculations (CHO). To analyze
      in vivo MRE measurements of the biceps brachii of healthy volunteers, different
      anisotropic fibrous structures for the couplings between the muscle elements have
      to be assumed. V-shaped wave patterns as observed when excitation was applied on
      the tendon were reproduced by a model, where in a central band of stiff fascicles
      wave propagation was about twice as fast as that in surrounding tissue. Planar
      waves were observed for excitation near the muscle surface. They could be
      reconstructed by assuming a simultaneous wave excitation of all muscle fibers,
      where fibers along the main muscle axis were coupled more strongly than those
      perpendicular to the axis. The results show that CHO calculations provide a fast
      and reliable method for incorporating anatomical information of the investigated
      tissue in the reconstruction of complex wave patterns.

PMID- 11973035
TI  - Investigation of insect morphology by MRI: assessment of spatial and temporal
      resolution.
AB  - Classically, the investigation of the internal morphology of insects relies on
      histologic methods, e.g., the preparation of thin tissue sections. However, the
      preparation of serial sections is time consuming and means the irreversible loss
      of the animal. In the present investigation, we have analyzed the potential of
      NMR imaging as a tool for the morphologic classification of insects with
      sufficient spatial resolution. With a 512 matrix, 15 mm FOV, 200 microm slice
      thickness, images with an in-plane spatial resolution of 30 microm are obtained
      with a signal-to-noise ratio of 70. These conditions require only seven averages,
      resulting in an experimental time of only 50 min. Such image quality already
      permits the differentiation of fine structural and morphologic details such as
      e.g., intestinal tracts and copulation organ in a beetle. Also, wing controlling
      dorsal muscle groups as well as leg structures and joints are clearly
      distinguishable. We conclude that the spatial resolution and contrast condition
      of MR imaging are quite promising for the new approach of zoological insect
      classification using NMR imaging. Further principally available technical
      enhancement of sensitivity and spatial resolution will provide an attractive
      alternative to invasive techniques for the classification of, sometimes, rare and
      precious insect specimen.

PMID- 11973036
TI  - In vivo proton magnetic resonance spectroscopy (MRS) study of post polio residual
      paralysis (PPRP) patients.
AB  - In-vivo proton MR spectroscopy carried out on post polio residual paralysis
      (PPRP) patients indicate that the presence or absence of intra-myocellular lipids
      (IMCL) is related to the severity of the paralysis. It is observed that mildly
      paralyzed patients are comparable (p > 0.05) with the control subjects in
      relation to the presence of IMCL, while moderate and severely paralysed patients
      are comparable (p > 0.05) in relation to the absence of IMCL. In addition, there
      is reduction or complete absence of creatine, carnitine and choline metabolites
      in severely paralyzed patients. The ability to detect noninvasively the subtle
      differences in in vivo, the lipid compartments of muscle may prove to be a
      valuable tool in understanding the pathogenesis of muscle diseases. This could
      open up the possibilities in designing effective rehabilitative exercise programs
      or development of new drug therapies.

PMID- 11973037
TI  - Fast two-dimensional MR imaging by multiple acquisition with micro B(0) array
      (MAMBA).
AB  - A new method for acquiring MR data in two dimensions is described. This is
      achieved by combining coils into an array so as to produce a unique local
      magnetic field within each coil when placed within the B(0) field of a standard
      MRI scanner. In this way each known location of a coil is associated with a
      unique resonant frequency. Each coil now represents a location of a pixel in the
      plane, and after Fourier transformation of the signal the resulting frequency
      spectrum gives immediately the spin distribution in the plane of the array. In
      effect, the two-dimensional spatial distribution is frequency encoded without the
      use of switched gradients or phase encoding. As only static fields are used, this
      technique offers the potential of fast imaging. Furthermore, signals from
      different locations would also be inherently time-registered. Initial experiments
      to demonstrate the principle are described, using a square array of 5 by 5 coils.
      The currents in the coils were determined by using a genetic algorithm. Echoes
      from pellet phantoms placed in the array were acquired using standard spin-echo
      sequences with gradients switched off. The results are promising, with the
      spectra showing generally good resolution between peaks, enabling localisation in
      up to half the pixels. Technical difficulties are discussed and possible
      applications are outlined.

PMID- 11973038
TI  - The effect of Gd-DTPA on T(1)-weighted choline signal in human brain tumours.
AB  - The influence of Gd-DTPA on T(1)-weighted (T(1)W) proton MR spectra has been
      investigated in 19 patients with histologically verified low (n = 13) or high
      grade (n = 6) gliomas. Repeat measurements were performed on 9 patients (7 low
      grade and 2 high-grade), with 28 examinations performed in total. Comparison of
      spectra obtained before and after 0.2 mmol/kg Gd-DTPA showed contrast agent
      induced broadening of the choline signal without significant signal area change.
      Lack of enhancement of the choline signal with the T(1)-weighted acquisitions
      implies that the contrast agent and the trimethylamine-containing species do not
      undergo significant direct interaction. Contrast agent induced changes in the
      choline signal observed in this and previous studies may, therefore, be
      attributable to T2*/susceptibility-based effects.

PMID- 11973039
TI  - Proton MR spectroscopy of basal ganglia in Wilson's disease: case report and
      review of literature.
AB  - Volume localized proton Magnetic Resonance Spectroscopy was carried out in both
      the left and right basal ganglia of three patients with clinically proven
      Wilson's Disease. While the untreated patient died 15 days after the spectroscopy
      study, the other 2 patients have been under treatment and have shown clinical
      improvement. The spectral features of the untreated patient were very different
      from those of the other two patients who were under treatment and responding.
      Asymmetrical changes in NAA and Cho were also observed for this patient.

PMID- 11973040
TI  - Primary epiploic appendagitis: MRI findings.
AB  - Primary epiploic appendagitis (PEA) occurs secondary to inflammation of an
      epiploic appendage, and is considered to be a rare cause of acute abdomen. In
      this case report, we describe the magnetic resonance imaging (MRI) findings of
      PEA correlated with computed tomographic (CT) findings. MRI findings included an
      oval shaped fat intensity mass with a central dot on T1- and T2-weighted images,
      which possessed an enhancing rim on postgadolinium T1-weighted fat saturated
      images. The lesion was best visualized on postcontrast T1-weighted fat saturated
      images. MRI findings of PEA should be considered in the differential diagnosis
      with the other causes of acute abdominal pain.

PMID- 11973042
TI  - An overview: the changing face of cutaneous infections and infestations.

PMID- 11973043
TI  - Cutaneous infections and infestations in historical (iconographic) perspective
      from variola to AIDS.

PMID- 11973044
TI  - Pemphigus and infections.

PMID- 11973045
TI  - The progress of venereology in Europe since the sixteenth century.

PMID- 11973046
TI  - Leishmaniasis and other dermatozoonoses in Brazil.

PMID- 11973047
TI  - Demodex folliculorum in development of dermatitis rosaceiformis steroidica and
      rosacea-related diseases.

PMID- 11973048
TI  - Where does syphilis stand in Croatia?

PMID- 11973049
TI  - Diagnosis of Lyme borreliosis by polymerase chain reaction.

PMID- 11973050
TI  - The great imitator: malignant syphilis with hepatitis.

PMID- 11973051
TI  - Chlamydia trachomatis: screening programs and the nucleic acid amplification
      assays.

PMID- 11973052
TI  - Molluscum contagiosum from infancy to maturity.

PMID- 11973053
TI  - Human papillomavirus male genital infections: clinical variations and the
      significance of DNA typing.

PMID- 11973054
TI  - The role of Malassezia furfur in dermatology.

PMID- 11973055
TI  - Current situation of tinea capitis in Southeastern Austria.

PMID- 11973056
TI  - Leprosy in Argentina.

PMID- 11973058
TI  - The cornea or the lens?

PMID- 11973060
TI  - Role of vitrectomy with optic capture.

PMID- 11973061
TI  - Role of vitrectomy with optic capture.

PMID- 11973063
TI  - Evaluating hydrophilic acrylic lenses.

PMID- 11973064
TI  - Intraocular pressure measurement after refractive surgery.

PMID- 11973067
TI  - Theoretical validity of vector analysis for aggregate astigmatic data.

PMID- 11973069
TI  - Anterior chamber maintainer versus viscoelastic material.

PMID- 11973070
TI  - Prophylactic measures prevalent in the United Kingdom.

PMID- 11973071
TI  - Posterior IOL dislocation after epilenticular IOL surgery.

PMID- 11973072
TI  - Scleral PC IOL fixation in children.

PMID- 11973074
TI  - Two-step nucleus rotation.

PMID- 11973073
TI  - Silicone oil bubbles in ophthalmic viscosurgical devices.

PMID- 11973075
TI  - Consultation section. Refractive surgical problem.

PMID- 11973083
TI  - Big-bubble technique to bare Descemet's membrane in anterior lamellar
      keratoplasty.
AB  - We describe a lamellar keratoplasty technique to bare Descemet's membrane in
      which air is injected to detach the central Descemet's. After a partial-thickness
      corneal trephination is performed, a disposable needle is inserted, deeply and
      bevel down, into the paracentral corneal stroma and air is injected. In most
      cases, this forms a large air bubble between Descemet's membrane and the corneal
      stroma. After anterior lamellar keratectomy is performed, a small opening is made
      in the air bubble and the remaining stromal layers are lifted with an iris
      spatula, severed with a blade, and excised with scissors. This technique is
      faster, safer, and easier to perform than previous methods.

PMID- 11973085
TI  - Spot size and quality of scanning laser correction of higher-order wavefront
      aberrations.
AB  - PURPOSE: To investigate the effect of laser spot size on the outcome of
      aberration correction with scanning laser corneal ablation. SETTING: Cleveland
      Clinic Foundation, Cleveland, Ohio, USA. METHODS: Corrections of wavefront
      aberrations of Zernike modes from the second to eighth order were simulated.
      Gaussian and top-hat beams of 0.6 to 2.0 mm full-width-half-maximum diameters
      were modeled. The fractional correction and secondary aberration (distortion)
      were evaluated. RESULTS: Using a distortion/correction ratio of less than 0.5 as
      a cutoff for adequate performance, a 2.0 mm or smaller beam was adequate for
      spherocylindrical correction (Zernike second order), a 1.0 mm or smaller beam was
      adequate for correction of up to fourth-order Zernike modes, and a 0.6 mm or
      smaller beam was adequate for correction of up to sixth-order Zernike modes.
      CONCLUSIONS: Since ocular aberrations above the Zernike fourth order are
      relatively insignificant in normal eyes, current scanning lasers with a beam
      diameter of 1.0 mm or less are theoretically capable of eliminating most higher
      order aberrations.

PMID- 11973084
TI  - Open-sky pupilloplasty during phakic penetrating keratoplasty to treat a fixed,
      dilated pupil.
AB  - We report a technique in which penetrating keratoplasty is performed in
      conjunction with open-sky pupilloplasty in a phakic patient. The technique was
      used in a 27-year-old man with poor vision and severe light sensitivity in the
      left eye dating back to an episode of presumed herpes simplex keratouveitis 13
      years previously. Examination showed a best corrected visual acuity of 20/40, a
      paracentral midstromal corneal scar, a fixed dilated pupil, and a clear lens.
      Postoperatively, the pupil was relatively round with a diameter of approximately
      4.0 mm, the cosmetic result was favorable, the photophobia had resolved, and the
      lens and corneal transplant were clear.

PMID- 11973086
TI  - Cataract surgery in allogeneic bone marrow transplant recipients with graft
      versus-host disease(1).
AB  - PURPOSE: To study the outcomes of cataract surgery in allogeneic bone marrow
      transplant recipients with documented graft-versus-host disease (GVHD) and to
      elucidate the concomitant ocular surface problems often encountered in these
      patients. SETTING: W.K. Kellogg Eye Center, University of Michigan, Ann Arbor,
      Michigan, USA. METHODS: This retrospective study comprised 12 cataract surgeries
      in 7 patients with GVHD) after allogeneic bone marrow transplantation. In
      particular, visual acuity improvement, surgical complications, and problems
      associated with concomitant ocular surface disease were reviewed. RESULTS: The
      mean visual acuity improved significantly from 20/46 (logMAR 0.32) preoperatively
      to 20/21 (logMAR 0.02) postoperatively (P <.005). The mean postoperative follow
      up was 23 months (range 3 to 48 months). All patients had dry eyes, and 3 had
      conjunctival cicatrization with mild keratinization. No patient had postoperative
      corneal breakdown. CONCLUSION: With aggressive management of dry eyes and other
      ocular surface problems, cataract surgery had excellent outcomes in patients with
      GVHD.

PMID- 11973087
TI  - Refractive lens exchange with the array multifocal intraocular lens.
AB  - PURPOSE: To study the safety and efficacy of refractive lens exchange as a
      refractive surgery modality in the presbyopic population. SETTING: Oregon Eye
      Institute, Eugene, Oregon, USA. METHODS: This retrospective review of patient
      charts included patient selection, preoperative evaluation, management of
      astigmatism, surgical technique, postoperative visual outcome, and complications.
      The study included 68 eyes comprising 32 bilateral and 4 unilateral refractive
      lens exchanges. RESULTS: All patients having bilateral refractive lens exchange
      achieved an uncorrected binocular visual acuity of 20/40 and J5 or better 1 to 3
      months postoperatively. More than 90% achieved an uncorrected binocular visual
      acuity of 20/30 and J4 and nearly 60%, of 20/25 and J3. CONCLUSION: Refractive
      lens exchange was a safe and effective refractive surgery modality in presbyopic
      patients.

PMID- 11973088
TI  - Long-term effect of phacoemulsification on intraocular pressure after
      trabeculectomy.
AB  - PURPOSE: To evaluate the effect of temporal clear corneal phacoemulsification on
      intraocular pressure (IOP) in eyes that have had trabeculectomy. SETTING:
      Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: This
      retrospective study evaluated the IOP in 48 eyes (35 patients) that had temporal
      clear corneal phacoemulsification after trabeculectomy. The mean interval between
      trabeculectomy and phacoemulsification was 27 months +/- 21 (SD) and the mean
      follow-up after phacoemulsification, 23 +/- 12 months. Intraocular pressure and
      antiglaucoma therapy before cataract surgery and at the end of follow-up were
      evaluated. For statistical analysis, the paired t test, Wilcoxon test, and chi
      square test were used. RESULTS: Thirty-five eyes (73%) preoperatively and 25 eyes
      (52%) postoperatively were controlled (IOP < 22 mm Hg) without antiglaucoma
      therapy. The difference was statistically significant (P =.04, chi-square test).
      At the end of follow-up, the increase in mean IOP (1.6 mm Hg) and in mean number
      of antiglaucoma medications (0.4) was statistically significant (P =.002 and P
      =.05, respectively). CONCLUSIONS: Temporal clear corneal phacoemulsification
      after trabeculectomy was followed by a slight but statistically significant
      increase in IOP and the need for antiglaucoma medication after 2 years. However,
      the impairment in IOP control is comparable to that in the natural course of
      trabeculectomy.

PMID- 11973089
TI  - Speed of capsular bend formation at the optic edge of acrylic, silicone, and
      poly(methyl methacrylate) lenses.
AB  - PURPOSE: To evaluate how and how fast a capsular bend is created clinically at
      the optic edge of an intraocular lens (IOL) after cataract surgery. SETTING:
      Jinshikai Medical Foundation, Nishi Eye Hospital, Osaka, Japan. METHODS: Capsular
      bend formation was observed by slitlamp after maximum pupil dilation in 45 eyes
      of 45 patients with senile cataract. Fifteen eyes each received an AcrySof MA60BM
      acrylic (Alcon), PhacoFlex II SI-40NB silicone (Allergan), or UV26T poly(methyl
      methacrylate) (PMMA) (Menicon) IOL. Patients were evaluated prospectively at 1
      day and 1, 2, and 4 weeks and retrospectively (15 eyes per IOL) 1 year after
      cataract surgery. A capsular bend index was developed to document and categorize
      the capsular bend formation process at the IOL optic edge. RESULTS: The anterior
      and posterior capsules adhered, with the latter attracted to the former. The
      adhesion always progressed from the periphery to the optic edge so that the
      posterior capsule eventually wrapped around the posterior optic edge, although
      not fully circumferentially in all cases. The process took place in 4 stages.
      Capsular bend formation was complete 1 month after surgery with the foldable IOLs
      (AcrySof, PhacoFlex II) but was significantly delayed with the PMMA IOL. After 1
      year, the capsular wrapping was firm and fully circumferential at the optic edge
      with all IOL types in all cases. CONCLUSIONS: Capsular bend formation progressed
      in the same fashion but at significantly different speeds among the IOLs,
      suggesting that the process depends on IOL material and design. Fast, early
      capsular bend formation may be 1 reason AcrySof and PhacoFlex II IOLs prevent PCO
      statistically better than PMMA IOLs. The results indicate that PCO is prevented
      by the sharp capsular bend created by sharp optic edges and by quick bend
      formation.

PMID- 11973090
TI  - Wavefront analysis of higher-order aberrations in patients with cataract.
AB  - PURPOSE: To determine local refractive changes and higher-order aberrations in
      patients with nuclear or cortical cataract. SETTING: Osaka University Medical
      School, Osaka, Japan. METHODS: Wavefront analysis of both ocular and corneal
      aberrations was performed with the Hartmann-Shack aberrometer in 2 patients, a 22
      year-old woman with bilateral developmental nuclear cataract and a 68-year-old
      woman with mild bilateral cortical cataract. RESULTS: Case 1 showed a delay in
      the wavefront that caused a myopic shift in the central pupillary area in both
      eyes, associated with the nuclear cataract. The spherical-like aberration (right
      eye, 36%; left eye, 21%) was greater than the coma-like aberration in both eyes.
      Case 2 showed an advancement of the wavefront that caused a hyperopic shift,
      especially in the lower temporal pupillary area, that was associated with the
      cortical cataract. The coma-like aberration (right eye, 63%; left eye, 52%) was
      greater than the spherical-like aberration in both eyes. The polarity of the
      third-order spherical aberration was negative in Case 1 and positive in Case 2.
      Corneal higher-order aberrations were small and had a different distribution than
      ocular higher-order aberrations in both patients. CONCLUSIONS: The Hartmann-Shack
      aberrometer was useful in detecting local refractive changes and higher-order
      aberrations in patients with mild cataract. The polarity and the absolute value
      of ocular higher-order aberrations may be useful parameters to characterize eyes
      with cataract.

PMID- 11973091
TI  - Visual function and outcomes after cataract surgery in a Singapore population.
AB  - PURPOSE: To identify the predictors of visual outcomes (visual acuity and visual
      function) in cataract surgery patients in Singapore and compare the visual
      outcomes of phacoemulsification and extracapsular cataract extraction (ECCE).
      SETTING: Singapore National Eye Center, Singapore, Republic of Singapore.
      METHODS: The visual function was measured by the VF-14 and visual acuity in the
      operated and the better eye in 460 systematically sampled cataract surgery
      patients preoperatively and 3 months after surgery. Several patient- and surgery
      related predictive factors were recorded. RESULTS: After cataract surgery, 85.1%
      of patients reported improved visual acuity in the operated eye and 77.6%
      reported improved visual function. Patients with poorer visual acuity and visual
      function at baseline reported greater improvements in visual acuity and visual
      function. Patients who had phacoemulsification had better final visual function
      (P =.006) and better final visual acuity (P <.001) scores. In multiple linear
      regression models, final visual function was better in patients without
      preexisting eye disease and with better baseline visual function, and final
      visual acuity in the operated eye was better in patients who were younger, were
      better educated, had no preexisting conditions or postoperative complications,
      and had a better baseline visual acuity. CONCLUSIONS: Patients with poorer
      baseline visual acuity or who had no preexisting eye disease reported more
      improvement in visual acuity in the operated eye. Several factors including no
      preexisting eye disease were associated with better final visual acuity and
      visual function scores.

PMID- 11973092
TI  - Treatment of interface keratitis with oral corticosteroids.
AB  - PURPOSE: To describe the results of treating interface keratitis using a
      combination of intensive topical and oral corticosteroids. SETTING: Casey Eye
      Institute, Portland, Oregon, USA. METHODS: Thirteen eyes treated for grade 2 to 3
      interface keratitis using an oral corticosteroid (prednisone 60 to 80 mg) as well
      as an hourly topical corticosteroid were retrospectively reviewed. The best
      corrected visual acuity (BCVA) was used as an objective guide of whether to treat
      with intense topical and oral corticosteroids, flap irrigation, or both.
      Predisposing factors such as intraoperative epithelial defects or a history of
      severe allergies or atopy were also looked for. RESULTS: All 13 eyes responded
      favorably to the combination of intensive topical and oral corticosteroids and
      had a BCVA of 20/20 after the keratitis resolved. In 6 eyes (46%), the patients
      had a history of severe seasonal allergies. One day postoperatively, 3 eyes (23%)
      had an epithelial defect and 2 eyes (15%), lint particles or debris embedded in
      the interface. With oral corticosteroid use, 3 patients (23%) noted mild stomach
      irritation and 2 (15%) noted nervousness. All 5 side effects resolved without
      sequelae. No patient developed a serious side effect. CONCLUSIONS: A short,
      intense course of an oral corticosteroid was an effective treatment in patients
      with grade 2 or higher interface keratitis when combined with a topical
      corticosteroid administered hourly. The BCVA is a helpful objective measure of
      the severity of interface keratitis and can be used to guide the clinician in the
      therapeutic strategy.

PMID- 11973093
TI  - Comparison of photorefractive keratectomy, astigmatic PRK, laser in situ
      keratomileusis, and astigmatic LASIK in the treatment of myopia.
AB  - PURPOSE: To determine factors affecting refractive and visual outcomes in
      patients treated with astigmatic and spherical photorefractive keratectomy (A-PRK
      and PRK) and laser in situ keratomileusis (A-LASIK and LASIK). SETTING:
      University referral refractive surgery clinic. METHODS: Refractive and visual
      acuity results in 619 eyes of 388 consecutive patients having refractive surgery
      over a 2-year period by a single surgeon were retrospectively analyzed. Patients
      were divided into mild-to-moderate myopia (spherical equivalent [SE] less than 
      6.12 diopters [D]) and high myopia (SE -6.12 D or higher). Multivariate and
      logistic regression analyses were performed. RESULTS: Refractive results in flap
      based and PRK-based procedures were comparable in mild-to-moderate myopia
      patients but were significantly better in high-myopia patients having flap-based
      procedures. Refractive stability was greater in flap-based procedures than in PRK
      based procedures. Elliptical ablations yielded a marked reduction in the
      astigmatic cylinder in patients having A-LASIK and A-PRK, while spherical PRK
      induced small amounts of with-the-rule astigmatism. Complications were uncommon
      in both groups, consisting primarily of epithelial ingrowth in flap-based
      procedures and haze in PRK-based procedures. Multivariate regression identified
      the preoperative SE as a significant determinant of PRK outcomes (with higher
      success for lower myopia) and intraocular pressure as a minor determinant of
      outcomes in PRK-based and flap-based procedures. Logistic regression suggested
      that only the preoperative SE was a significant factor in predicting the
      likelihood of poor outcomes in PRK patients. CONCLUSIONS: Refractive outcomes
      were almost identical in patients having elliptical or spherical ablations with
      flap-based or PRK-based procedures. In eyes with mild-to-moderate myopia, there
      was little difference in refractive or visual outcomes between flap-based and PRK
      based procedures; in eyes with high myopia, flap-based procedures offered more
      predictable refractive outcomes and better visual outcomes.

PMID- 11973094
TI  - Astigmatic changes after excimer laser refractive surgery.
AB  - PURPOSE: To compare the astigmatic changes induced by spherical and elliptical
      excimer laser in situ keratomileusis (LASIK) and photorefractive keratectomy
      (PRK). SETTING: University-based refractive surgery practice. METHODS: Three
      month refractive data from 317 eyes of consecutive patients having spherical PRK,
      astigmatic PRK (A-PRK), spherical LASIK, and astigmatic LASIK (A-LASIK) by a
      single surgeon (J.S.P.) using VISX 2020B and Star lasers over 2 years were
      studied for astigmatic changes resulting from the surgical procedure. RESULTS: At
      3 months, the mean change in absolute astigmatism was +0.15 diopter (D) and -0.07
      D in the spherical PRK and LASIK groups, respectively. Photorefractive
      keratectomy tended to induce with-the-rule (WTR) astigmatism, while LASIK was
      astigmatically neutral. As expected, the eyes treated with A-PRK and A-LASIK
      achieved a greater reduction in absolute astigmatism (-1.02 D and -1.28 D,
      respectively) than those treated with spherical PRK and LASIK. The qualitative
      nature of the astigmatic change was different between flap-based and PRK-based
      procedures. CONCLUSIONS: Spherical PRK is more likely than spherical LASIK to
      induce astigmatism, with a tendency toward WTR astigmatism. The eyes treated with
      spherical LASIK had no preponderant change in the direction of astigmatic
      magnitude or axis. Astigmatic PRK and LASIK effectively reduced astigmatism along
      the preoperative axis; A-LASIK tended to induce a random resultant axis in most
      patients.

PMID- 11973095
TI  - Laser in situ keratomileusis for myopia and compound myopic astigmatism using the
      Technolas 217 scanning-spot laser.
AB  - PURPOSE: To evaluate the safety, efficacy, predictability, and visual results of
      laser in situ keratomileusis (LASIK) using the Bausch & Lomb Technolas(R) 217
      scanning-spot laser for the treatment of myopia and compound myopic astigmatism.
      SETTING: Stanford Eye Laser Center, Stanford, California, USA. METHODS: In a
      prospective study, 110 eyes of 58 patients with a mean spherical equivalent (SE)
      of -4.87 diopters (D) +/- 2.5 (SD) (range -1.0 to -11.4 D) had LASIK for myopia
      and compound myopic astigmatism using the Technolas 217 scanning-spot laser. The
      primary outcome variables included preoperative and postoperative best spectacle
      corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA), achieved
      versus attempted correction, vector analysis of astigmatism, and complications.
      RESULTS: One hundred ten eyes were available for analysis at 3 months. The mean
      SE refraction was reduced 95% (mean -0.23 +/- 0.4 D), and astigmatism was reduced
      70% (mean 0.28 +/- 0.3 D). One day postoperatively, 100% of eyes had a UCVA of
      20/40 or better, 96% had 20/25 or better, 77% had 20/20 or better, and 39% had
      20/15 or better. At the 3-month examination, 100% of eyes had a UCVA of 20/40 or
      better, 95% had 20/25 or better, 83% had 20/20 or better, and 48% had 20/15 or
      better. Ninety percent of eyes were within +/-0.5 D of emmetropia. No eye lost 2
      or more lines of BSCVA. CONCLUSIONS: The Technolas 217 scanning-spot laser
      produced excellent postoperative UCVA and BSCVA. It was predictable, safe, and
      effective for the treatment of myopia and compound myopic astigmatism. Long-term
      follow-up is needed to assess the stability of the procedure.

PMID- 11973097
TI  - Minimal astigmatism after sutureless planned extracapsular cataract extraction.
AB  - PURPOSE: To evaluate astigmatism after mini-nuc extracapsular cataract extraction
      (ECCE) in which a chevron incision is enlarged to 6.0 to 7.0 mm for easier
      nucleus removal and to compare the results with those using a 5.0 mm incision.
      SETTING: Department of Ophthalmology, The Edith Wolfson Medical Center, Sackler
      Faculty of Medicine, Tel-Aviv University, Holon, Israel. METHODS: Thirty eyes of
      29 patients were enrolled in this study. Keratometry was performed preoperatively
      and 3 to 9 months postoperatively. The incision length was 6.0 mm in 6 eyes, 6.5
      mm in 10 eyes, and 7.0 mm in 14 eyes that had mature cataract. RESULTS: The mean
      induced astigmatism calculated by simple subtraction was 0.12 diopter (D) +/-
      0.51 (SD), 0.16 +/- 0.98 D, and 0.67 +/- 0.91 D for the 6.0 mm, 6.5 mm, and 7.0
      mm incision, respectively. By vector analysis, the mean induced astigmatism was
      0.60 +/- 0.30 D, 0.75 +/- 0.67 D, and 1.36 +/- 0.77 D, respectively. Results by
      both methods showed no significant difference between the previously reported 5.0
      mm incision and the 6.0 mm and 6.5 mm incisions. The 7.0 mm group had
      statistically significantly greater induced astigmatism than the 5.0 mm group (P
      =.01, simple subtraction; P =.002, vector analysis). CONCLUSIONS: Enlarging the
      size of the chevron incision up to 7.0 mm resulted in a small increase in induced
      astigmatism. The enlarged incision simplified the operative technique.

PMID- 11973096
TI  - Corneal astigmatic change after photorefractive keratectomy and photoastigmatic
      refractive keratectomy.
AB  - PURPOSE: To evaluate and compare the efficacy, safety, predictability, and
      surgically induced astigmatism (SIA) of photorefractive keratectomy (PRK) and
      photoastigmatic refractive keratectomy (PARK). SETTING: Department of
      Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. METHODS: In
      this retrospective study, 70 eyes were treated for myopia and 70 eyes were
      treated for myopic astigmatism. Refraction, corneal topography, slitlamp
      findings, and visual acuity in the 2 groups at 1, 3, and 6 months were evaluated
      and compared. Vector analysis was performed to determine the SIA in both groups.
      RESULTS: The mean preoperative spherical equivalent at the glasses plane in the
      PRK and PARK groups was -6.06 diopters (D) and -7.18 D, respectively. At 6
      months, the mean reduction in astigmatism in the PARK group was 61.0%.
      Predictability was within +/-1.0 D in 85.2% of eyes in the PRK group and 62.5% in
      the PARK group. An uncorrected visual acuity of 20/40 or better was achieved in
      91.8% and 83.9% of eyes, respectively. The mean SIA was 0.64 D in the PRK group,
      with a general with-the-rule axis shift. The results of vector analysis were more
      favorable when calculated from refractive values than from Sim-K corneal
      topography values. The mean astigmatism correction index and index of success
      calculated from refractive data were 0.75 and 0.38 in the PARK group. The mean
      magnitude and angle of error were 0.22 +/- 0.52 D and -2.13 +/- 24.41 degrees,
      respectively. CONCLUSIONS: Photorefractive keratectomy and PARK were effective
      and safe procedures for the correction of myopia and myopic astigmatism. However,
      SIA occurred with spherical myopic treatments. This small SIA may be a
      confounding factor in low astigmatic treatments.

PMID- 11973098
TI  - Axial length in applanation tonometry.
AB  - PURPOSE: To investigate the clinical applicability of a physical principle that
      suggests that a large globe offers less resistance to applanation than a smaller
      one. SETTING: Referral practice, Bridgeport, Connecticut, USA. METHODS: The
      correlation between axial length and applanation tonometry in 513 adult eyes,
      arbitrarily chosen from a referral practice, was examined using regression
      analysis. RESULTS: A statistically significant negative correlation was found;
      that is, for every 1.0 mm increase in axial length, the tonometry value was 0.29
      units lower (P =.0002). In women, the mean axial length was 1.04 mm shorter and
      the mean intraocular pressure 0.54 mm Hg higher than in men. CONCLUSIONS: Globe
      size influenced applanation tonometry readings. Hence, when the tonometry record
      does not fit the clinical findings, axial length measurement may help interpret
      its significance.

PMID- 11973099
TI  - Nitric oxide levels in the aqueous humor in cataract patients.
AB  - PURPOSE: To determine the role of nitric oxide (NO) in the clinical
      manifestations of cataract in different age and etiological groups. SETTING:
      Multicenter study, Taipei, Taiwan, Republic of China. METHODS: Aqueous humor
      samples were obtained from 114 cataract patients in different etiological and age
      groups (eg, juvenile, traumatic, and age-related cataract). Using
      chemiluminescence assay, NO was detected through the light generated by ozone and
      NO interaction. The amount of NO production was calculated and compared among
      groups. The results were correlated with patient age. RESULTS: The NO levels in
      aqueous humor were highest in the 12 patients with traumatic cataract and lowest
      in the 15 patients with juvenile cataract (47.59 micromol/L +/- 12.81 [SD] and
      7.66 +/- 2.62 micromol/L, respectively; P <.001). Aqueous humor NO levels were
      correlated with age and were highest in patients older than 80 years (mean 38.78
      +/- 6.29 micromol/L) and in those with mature cataract (mean 40.15 +/- 6.15
      micromol/L) (P <.05). CONCLUSIONS: The NO levels in the aqueous humor increased
      with age and traumatic events. The results suggest that NO could be a risk factor
      in cataract formation.

PMID- 11973101
TI  - Topical ketorolac tromethamine 0.5% versus diclofenac sodium 0.1% to inhibit
      miosis during cataract surgery.
AB  - PURPOSE: To compare the effect of topical ketorolac tromethamine 0.5% solution
      and topical diclofenac sodium 0.1% solution on the inhibition of surgically
      induced miosis. SETTING: Tertiary care teaching hospital in South India. METHODS:
      Fifty-one patients were prospectively randomized to receive ketorolac 0.5% or
      diclofenac 0.1% at 3 intervals preoperatively. Patients with diabetes mellitus,
      pseudoexfoliation, or local pupil abnormalities were excluded from the study.
      Mydriatics comprising homatropine 1% plus phenylephrine 10% were instilled in all
      patients 1 hour before the peribulbar block at 5 intervals. Horizontal pupil
      diameters were obtained at the beginning of surgery, after capsulotomy, after
      intraocular lens (IOL) implantation, and at the end of surgery. RESULTS: The mean
      horizontal pupil diameter was 7.40 mm at the start of surgery in both groups. The
      ketorolac group showed a consistent trend toward larger pupil diameters at
      subsequent surgical intervals. Changes from baseline also indicated more
      significant inhibition of miosis in the ketorolac group. CONCLUSIONS: Topical
      ketorolac was a more effective inhibitor of miosis than topical diclofenac during
      extracapsular cataract extraction and IOL implantation. It also provided a more
      stable mydriatic effect throughout surgery.

PMID- 11973100
TI  - Carticaine versus lidocaine for peribulbar anesthesia in cataract surgery.
AB  - PURPOSE: To compare carticaine 4% and lidocaine 2% for peribulbar anesthesia in
      cataract surgery. SETTING: Ain Shams and Cairo University Hospitals, Cairo,
      Egypt. METHODS: This prospective double-blind randomized study comprised 200
      cataract patients assigned to 1 of 2 groups of 100 each based on type of
      anesthesia: carticaine 4% or lidocaine 2%. The efficacy, safety, and duration of
      the motor and the analgesic block produced by carticaine 4% adrenaline
      hyaluronidase mixture and lidocaine 2% adrenaline hyaluronidase mixture used as
      peribulbar anesthesia were compared. The mean time for satisfactory block, need
      for supplementary injections, incidence of intraoperative and postoperative pain,
      and postoperative complications were evaluated. The data were analyzed using the
      Student t test and Mann-Whitney U test for intergroup differences. The chi-square
      or Fisher exact test was used to assess eye movement scores, the need for
      supplementary injections, the onset of postoperative pain, and the incidence of
      postoperative complications. RESULTS: The mean time for satisfactory anesthesia
      was 7.5 minutes +/- 1.68 (SD) for lidocaine 2% and 2.5 +/- 1.53 minutes for
      carticaine 4% (P <.001). The need for supplementary injections was 28% in the
      lidocaine group and 4% in the carticaine group (P <.001). The mean onset of
      postoperative pain was 2.00 +/- 0.86 hours in the lidocaine group and 5.52 +/-
      1.80 hours in the carticaine group (P <.05). There were no cases of postoperative
      neurotoxicity or extraocular muscle dysfunction in either group. CONCLUSIONS:
      Carticaine 4% adrenaline hyaluronidase mixture was an effective and safe agent
      for peribulbar anesthesia. It was more efficient than lidocaine 2% adrenaline
      hyaluronidase mixture in the onset and quality of anesthesia as well as
      postoperative analgesia.

PMID- 11973103
TI  - Correction of hyperopia with intracorneal implants.
AB  - PURPOSE: To evaluate the safety and efficacy of intracorneal lenses as a surgical
      alternative for the correction of hyperopia. SETTING: Al-Azhar University, Cairo,
      Egypt, and Louisiana State University Eye Center, New Orleans, Louisiana, USA.
      METHODS: PermaVision lenses (Anamed Inc.) were implanted in the left eye of 20
      albino rabbits that were followed for 6 months by confocal microscopy. The lenses
      are made of a highly permeable hydrogel with 70% water content and a refractive
      index close to that of corneal tissue (1.376). The Carriazo-Barraquer
      microkeratome (Moria) was used to create a 150 microm corneal flap with a
      diameter of 8.5 mm or larger. The intracorneal lens was placed under the flap
      after minimal interface irrigation. RESULTS: At 3 days, confocal microscopy
      showed interface edema that resolved after 1 week. No flap melting or excursion
      of the lens was noted. In 1 eye, a deep lamellar keratitis was seen. At 6 months,
      the edge of the lens showed excellent compatibility, with no keratocytic activity
      or intrastromal fibrosis. CONCLUSIONS: Intracorneal hydrogel lenses were well
      tolerated by stromal tissue in rabbits. They are potentially safe and can be
      considered as an alternative for the correction of hyperopia. Further clinical
      studies are required to confirm their safety in humans.

PMID- 11973102
TI  - Implantation and capsular bag stability of single-piece, foldable EasAcryl 1
      intraocular lenses.
AB  - PURPOSE: To assess the folding and implantation of the single-piece EasAcryl 1
      intraocular lens (IOL) and the maintenance of the tunnel structure and capsular
      bag stability after implantation. SETTING: S. Orsola Hospital Department of
      Pathophysiologic Optics, University of Bologna, Bologna, Italy. METHODS: This
      study comprised 300 cases of EasAcryl 1 IOL implantation. First, a 3.2 mm corneal
      incision was made according to preoperative astigmatism followed by a 5.5 mm +/-
      0.3 (SD) capsulorhexis. After sutureless phacoemulsification using a venturi
      pump, the 6.0 mm optic, 11.0 mm diameter IOL was implanted using a hexagonal
      cartridge. The IOLs were implanted using a 2-step maneuver when the superior
      haptic was grasped with the forceps (first case) or a 1-step maneuver when only
      the Microsert injector was used. The cartridge was never pushed beyond the
      tunnel. The preoperative and postoperative incision size and the corneal
      surgically induced astigmatism were recorded. The IOL rotation was measured 30 +/
      5 days and 8 +/- 1 months postoperatively. RESULTS: No intraoperative
      complications occurred after the learning curve. No alteration in astigmatism was
      observed. The mean IOL rotation was 1.04 +/- 0.5 degrees at 30 +/- 5 days and
      1.02 +/- 0.2 degrees at 8 +/- 1 months. CONCLUSIONS: The EasAcryl 1 was easily
      implantation through a 3.2 mm tunnel without altering the natural architecture.
      The unfolding of the IOL was well controlled, and the IOL remained well centered.
      A short learning curve is required.

PMID- 11973104
TI  - Endothelial protection: avoiding air bubble formation at the phacoemulsification
      tip.
AB  - PURPOSE: To investigate the conditions under which bubbles form during
      phacoemulsification. SETTING: Department of Ophthalmology, Yonsei University
      College of Medicine, Seoul, Korea. METHODS: In the first part of the study, the
      partial pressure of oxygen (pO(2)) was used as a surrogate measure for the
      partial pressure of air. Irrigation solutions packaged in glass and plastic
      containers were studied. A directly vented glass bottle was also tested. The
      pO(2) of the various irrigation solutions was measured as the containers were
      emptied. In the second part, phacoemulsification procedures were performed in
      rabbit eyes with different power settings and different irrigation solutions.
      Intracameral bubble formation during the procedure was recorded. Following the
      phacoemulsification procedures, the corneas were stained for F-actin and examined
      for endothelial injury. RESULTS: The initial pO(2) in irrigation solutions
      packaged in glass bottles was about half that at atmospheric levels; in solutions
      packaged in plastic, it was at atmospheric levels. As irrigation solutions were
      drained from the container, the pO(2) of the solution tended to rise toward
      atmospheric levels. The rate of pO(2) increase was markedly reduced by using a
      directly vented glass bottle. In the phacoemulsification procedures, bubble
      formation was most likely to occur with higher pO(2) and higher power settings.
      Observation of bubbles by the surgeon was highly correlated with endothelial
      damage. CONCLUSIONS: Keeping the pO(2) low reduced the risk of endothelial
      damage, especially at higher phacoemulsification powers. The packaging of
      irrigation solutions was the most important factor in controlling the initial
      pO(2) of the solution. The pO(2) can be minimized throughout a
      phacoemulsification procedure by using a directly vented glass bottle.

PMID- 11973105
TI  - Cytopathology of explanted intraocular lenses and the clinical correlation.
AB  - PURPOSE: To study the cytopathological features of explanted intraocular lenses
      (IOLs) and correlate the features with their clinical presentation. SETTING:
      Ocular Pathology Department, Medical and Vision Research Foundation, Sankara
      Nethralaya, Chennai, India. METHODS: The study comprised 61 explanted IOLs (48
      posterior chamber IOLs and 13 anterior chamber IOLs) removed for the following
      reasons: pseudophakic bullous keratopathy (36), recalcitrant uveitis (7), retinal
      detachment (10), endophthalmitis (5), uveitis (7), IOL subluxation (2), and
      painful blind eye (1). The IOLs were stained with hematoxylin and eosin using a
      simple cytological technique. The cytopathological features were studied and
      correlated with the clinical presentations. RESULTS: The mean time of IOL
      explantation was 10.1 months after surgery. Twenty-one IOLs had granulomatous and
      nongranulomatous inflammations and 4, nongranulomatous inflammations. One IOL had
      fungal filaments on the surface. CONCLUSIONS: Intraocular lenses can produce both
      granulomatous and nongranulomatous inflammation. Granulomatous inflammation was
      the most common in this series. The surface of IOLs explanted because of
      intraocular infection may show infective agents.

PMID- 11973106
TI  - Laser in situ keratomileusis in a patient with congenital nystagmus.
AB  - We report the results of laser in situ keratomileusis (LASIK) to correct myopia
      in a 47-year-old woman with congenital motor nystagmus and myopia. The patient
      had simultaneous bilateral LASIK using the Alcon-Summit-Autonomous LADARVision
      excimer laser. Her uncorrected visual acuity (UCVA) preoperatively was 20/600 in
      the right eye and 20/800 in the left eye; best corrected visual acuity was 20/40
      in both eyes. Twelve months after bilateral LASIK, with an enhancement procedure
      in both eyes at 4 months, UCVA was 20/40 in both eyes. Corneal topography showed
      well-centered ablation zones.

PMID- 11973107
TI  - Correcting high astigmatism with piggyback toric intraocular lens implantation.
AB  - An 86-year-old man presented for cataract surgery with corneal astigmatism of
      5.12 diopters (D). After cataract extraction with small-incision techniques, 2
      toric plate-haptic silicone intraocular lenses (IOLs) were implanted in the
      capsular bag, each with a 3.50 D cylinder add (2.30 D at the spectacle plane).
      Six weeks postoperatively, corneal astigmatism was 3.38 D at 70 degrees and
      refractive astigmatism was 1.00 D at 20 degrees. Uncorrected visual acuity was
      20/40. No IOL rotation was observed. Implantation of piggybacked toric lenses may
      be a viable option for correcting moderate to high astigmatism.

PMID- 11973108
TI  - Pneumococcal keratitis at the flap interface after laser in situ keratomileusis.
AB  - A 28-year-old woman had uneventful laser in situ keratomileusis in the right eye.
      Six days postoperatively, she reported ocular pain and a large corneal stromal
      infiltrate was observed at the flap interface. A second surgery including lifting
      and excising the flap and scraping the stromal bed was performed. Topical
      antibiotics were prescribed. A bacterial culture revealed Streptococcus
      pneumoniae. The keratitis responded well to topical vancomycin. Twelve days after
      the second surgery, the stromal infiltrate had regressed, the hypopyon had
      resolved, and visual acuity was hand movements at 0.5 m.

PMID- 11973109
TI  - Iatrogenic keratoconus as a complication of radial keratotomy.
AB  - A 47-year-old man with a family history of keratoconus had uneventful bilateral
      radial keratotomy (RK) with astigmatic keratotomy (AK) enhancements 12 years
      earlier. He noticed a gradual onset of blurry vision with progressively
      increasing myopic shift. Visual acuity remained poor even with spectacles or soft
      contact lenses. Slitlamp examination revealed 16 well-healed RK scars and 2 AK
      scars with marked corneal steepening inferiorly in an area of astigmatic
      enhancement in the left eye but an otherwise normal fellow eye with 16 well
      healed RK scars. He subsequently had penetrating keratoplasty for decreased
      vision not correctable by rigid gas-permeable contact lenses. Microscopic
      examination of the corneal button showed findings consistent with keratoconus.
      This case represents the first documented incidence of corneal ectasia as a
      complication of primary RK.

PMID- 11973110
TI  - Ocular explosion after peribulbar anesthesia.
AB  - We report 3 cases of globe rupture after peribulbar anesthesia. We discuss the
      predisposing factors, presenting features, and visual outcome after this
      complication. Globe explosion is a severe complication of inadvertent intraocular
      injection during peribulbar anesthesia. Visual outcome after vitrectomy is
      generally poor; however, cases that do not develop a retinal detachment may
      achieve good results.

PMID- 11973111
TI  - Inadvertent ocular perforation and intravitreal injection of an anesthetic agent
      during retrobulbar injection.
AB  - We report the clinical management of a patient who sustained scleral perforation
      and intraocular injection of local anesthetic agent during retrobulbar block. We
      discuss the management options for this rare complication of local anesthesia in
      cataract surgery.

PMID- 11973112
TI  - Nonaccommodative esotropia after cataract extraction in a patient with previous
      accommodative esotropia.
AB  - We report a case of nonaccommodative esotropia developing after bilateral
      cataract surgery that corrected the preexisting hyperopia in a patient with
      accommodative esotropia since childhood. The esotropia required surgical
      correction despite the good visual acuity after the cataract surgery. In patients
      with preexisting strabismus, there is a possibility of decompensation of adaptive
      binocular mechanisms after cataract surgery and refractive procedures.

PMID- 11973113
TI  - Child and Adolescent Psychiatric Screening Inventory-Retrospect (CAPSI-R): a
      questionnaire for adults concerning child and adolescent mental disorders.
AB  - This study examines the properties of the Child and Adolescent Psychiatric
      Screening Inventory-Retrospect, CAPSI-R, a self-report 146-item questionnaire for
      adults concerning earlier child psychiatric symptoms, comprising both DSM-IV
      categories and functional impairment. The instrument was mailed to 359 former
      child psychiatric patients born between 1951 and 1977 (164 of whom responded) and
      to a matched control group (193 of whom responded). There was good internal
      consistency (Cronbach's alpha ranged between 0.62-0.93, and between 0.76-0.93
      after elimination of one item). The lifetime prevalence of a mental disorder was
      87.8% in the former patients' without considering impairment and 76.8% when
      impairment was considered. The corresponding figures for the control group were
      49.7% and 10.4%, respectively. When the former patients' CAPSI-R diagnoses (with
      incorporation of the impairment criterion) were validated against the DSM-IV
      diagnoses based on information in their medical records, generally, an acceptable
      sensitivity and specificity were obtained. The overall kappa between CAPSI-R
      diagnoses and those from medical records was 0.79. The CAPSI-R shows promise for
      further evaluation and may be useful in recognising child and adolescent mental
      disorders in adults.

PMID- 11973114
TI  - Lexical decision tasks in depressive patients: semantic priming before and after
      clinical improvement.
AB  - This study was designed to evaluate the effect of semantic priming with a lexical
      decision task in 22 depressed patients (DSM-III-R, 1987) and 30 control subjects.
      These patients were evaluated twice: first when they arrived at the hospital, and
      secondly, after clinical improvement. Clinical improvement was evaluated using
      standard depression rating scales. A lexical decision task involving semantic
      relations (related vs. unrelated, e.g., apple-pear) was used to evaluate the
      processing of semantic information. The results showed that, for the first
      evaluation, the depressives presented similar semantic priming to control
      subjects. When we compared semantic priming in the first and the second passes,
      we observed that its amplitude was identical. The sole difference between the two
      passes concerns the global reaction time in the depressive group. This last
      result suggested that, with clinical improvement, the characteristic psychomotor
      retardation declines. One of the major results concerns the fact that severe
      depressive patients (first pass) exhibit normal semantic priming in a lexical
      decision task. These results indicate, in this clinical population, the
      preservation of controlled processes implicated in this lexical decision task.

PMID- 11973115
TI  - Validation of the Computerized Suicide Risk Scale--a backpropagation neural
      network instrument (CSRS-BP).
AB  - BACKGROUND: Medically serious suicide attempts have been recognized as the most
      important predictor of suicide. The Computerized Suicide Risk Scale based on
      backpropagation neural networks (CSRS-BP) has been recently found efficient in
      the detection of records of patients who performed medically serious suicide
      attempts (MSSA). OBJECTIVES. To validate the CSRS-BP by: 1) using the CSRS-BP
      with patients instead of records; 2) comparing the ability of expert
      psychiatrists to detect MSSA, using the CSRS checklist; and 3) comparing the
      results of the Risk Estimator for Suicide (RES) and the self-rating Suicide Risk
      Scale (SRS) with the CSRS-BP. METHODS: Two hundred fifty psychiatric inpatients
      (35 MSSA and 215 non-MSSA) were diagnosed by clinicians using the SCID DSM-IV.
      Three expert psychiatrists completed the CSRS checklist, and the RES for each
      patient, and the patients completed the self-report SRS assessment scale. The
      CSRS-BP was run for each patient. Five other expert psychiatrists assessed the
      CSRS checklists and estimated the probability of MSSA for each patient.
      Comparisons of sensitivity and specificity rates between CSRS-BP, assessment
      scales and experts were done. RESULTS: Initially, the CSRS-BP, RES, SRS, and
      experts performed poorly. Although sensitivity and specificity rates
      significantly improved (two to four times) after the inclusion of information
      regarding the number of previous suicide attempts in the input data set, results
      still remained insignificant. CONCLUSIONS: The CSRS-BP, which was very successful
      in the detection of MSSA patient records, failed to detect MSSA patients in face
      to-face interviews. Information regarding previous suicide attempts is an
      important MSSA predictor, but remains insufficient for the detection of MSSA in
      individual patients. The detection rate of the SRS and RES scales was also poor
      and could therefore not identify MSSA patients or be used to validate the CSRS
      BP.

PMID- 11973117
TI  - Lithium: poisonings and suicide prevention.
AB  - This study concerns 81 cases of lithium poisoning and shows that deliberate
      intoxications are prevalent during the first 3 years of lithium treatment as well
      as in cases with a previous history of suicide attempt. Therapeutic intoxications
      could generally be avoided by education concerning hygiene and diet and careful
      monitoring in cases of intercurrent diseases.

PMID- 11973116
TI  - Telephone contact with patients in the year after a suicide attempt: does it
      affect treatment attendance and outcome? A randomised controlled study.
AB  - Ambivalence to treatment and repeated suicidal behaviour are well-known problems
      in suicide attempters. A randomised controlled study was performed to investigate
      the influence of repeated telephone contacts on treatment attendance, repetition
      of suicidal behaviour and mental health the year after a suicide attempt.
      SUBJECTS AND METHODS: One month after their suicide attempt 216 patients were
      randomised to either two telephone interventions in addition to treatment as
      usual, or no such intervention during the subsequent year. The interventions
      included motivational support to attend and/or to stay in treatment. At 1 month
      and again after 12 months the following measurements were used: GSI (SCL-90), GAF
      and SSI. RESULTS: At follow-up treatment attendance was high and did not differ
      between the randomised groups. Among those with an initial treatment contact
      other than psychiatric, more patients in the intervention group had such contact
      at follow-up. The randomised groups did not differ in repetition of suicide
      attempts during follow-up or in improvement in GSI (SCL-90), GAF and SSI. In
      individuals with no initial treatment the intervention group improved more in
      certain psychological symptom dimensions (SCL-90). CONCLUSION: Telephone
      interventions seem to have an effect on patients who at their suicide attempt had
      other treatment than psychiatric and in those with no treatment.

PMID- 11973118
TI  - Risperidone in the treatment of psychoses in the elderly: a case report series.
AB  - Risperidone is one of the newer atypical antipsychotic agents, which combines
      potent serotonin and dopamine receptor antagonism. It shows efficacy against the
      positive and negative symptoms of schizophrenic psychoses and other psychotic
      conditions, and has a low propensity to cause extrapyramidal side effects. The
      aim of these case reports in elderly patients is to provide the benefit of
      personal experience with risperidone to the body of published literature and to
      demonstrate the types of patients that may benefit from treatment. These cases
      were compiled retrospectively from data collected on referral and during routine
      hospital appointments. This series covers four main areas of concern when
      treating the elderly: low-maintenance dosing minimising the likelihood of adverse
      events; successful treatment of patients previously uncontrolled and experiencing
      side effects with other antipsychotics; the possibility of intermittent rather
      than continuous treatment; and the benefits to patients, carers and the health
      services. At low doses, risperidone is an effective and well-tolerated treatment
      for psychoses in elderly patients that improves the quality of life for both
      patients and their caregivers.

PMID- 11973119
TI  - Antihormonal treatment of paraphilic patients in German forensic psychiatric
      clinics.
AB  - The aim of this study was to investigate which antihormonal treatment strategies
      are used in German forensic psychiatric institutions. Forensic clinics were asked
      about the number of treated patients. Four hundred seventy-four patients were
      committed for sex offences; 12% received either CPA (n = 29) or LHRH- agonists (n
      = 29). Differences in efficacy were small. Several side effects confirm the
      importance of a protocol for minimizing medical complications.

PMID- 11973120
TI  - Mirtazapine overdose with benign outcome.

PMID- 11973121
TI  - Biological basis and staging of Cotard's syndrome.

PMID- 11973125
TI  - Formation and function of the immunological synapse.
AB  - Less than five years ago it was reported that cell surface molecules at the
      contact site between CD4 T cells and antigen-presenting cells redistribute into
      distinct patterns, forming an organized interface termed the immunological
      synapse. More recently, similar reorganized interfaces have been observed with
      CD8 T cells and NK cells, suggesting that they may be a common feature of
      lymphocyte activation. Although there has been some advance in our understanding
      of the mechanisms underlying this redistribution, its purpose remains unclear and
      controversial.

PMID- 11973126
TI  - The T-cell receptor signalosome: a dynamic structure with expanding complexity.
AB  - Signal transduction in T cells is a dynamic process involving a large number of
      membrane and cytosolic proteins. The TCR macromolecular complex (signalosome) is
      initiated by receptor occupancy and becomes more elaborate over time. This review
      describes how 'vertical' displacement mechanisms and lateral coalescence of lipid
      raft-associated scaffold proteins combine to form distinct signalosomes, which
      control signal specificity.

PMID- 11973127
TI  - Lymphocyte activation via NKG2D: towards a new paradigm in immune recognition?
AB  - NKG2D is an activating cell surface receptor expressed on a wide range of immune
      effector cells including NK cells, NKT cells, gammadelta T cells as well as
      CD8(+) alphabeta T cells. Recent data indicate two major features: first, that
      human (MICA, MICB and ULBP) and mouse (Rae1 and H60) NKG2D ligands can be induced
      and/or upregulated upon cellular distress; and second, that on T cells NKG2D
      serves as a co-stimulation molecule for TCR triggering, whereas on NK cells NKG2D
      may act as a primary recognition structure.

PMID- 11973128
TI  - Scaffolds, adaptors and linkers of TCR signaling: theory and practice.
AB  - Four non-enzymatic proteins form the structural core of the TCR signaling
      machinery, linking antigen-receptor activation to signaling. These four proteins,
      each with well defined protein-protein interaction domains, include three
      'scaffolds' (LAT, SLP-76 and SLAP-130/Fyb/ADAP and a 'pure adaptor' (GADS). The
      biological functions of many distinct protein-protein interaction domains have
      been dissected through a methodological series of knockout and reconstitution
      experiments. In reviewing these recent advances, we attempt to address two
      questions often asked by immunologists not familiar with the field: what do
      scaffolds/adaptors/linkers do; and what do these terms mean?

PMID- 11973129
TI  - Communication between the TCR and integrins: role of the molecular adapter
      ADAP/Fyb/Slap.
AB  - TCR stimulation induces integrin-mediated adhesion, facilitating stabilization of
      conjugates between T cells and antigen-presenting cells and thereby contributing
      to T cell activation. Integrin activation has been shown to require cytoskeletal
      reorganization; however, the molecular mechanisms mediating communication between
      the TCR and integrins remain unclear. Recently the adapter protein ADAP/Fyb/Slap
      has been shown to couple TCR stimulation to integrin activation by mediating
      increased integrin avidity. ADAP may also play a role in transduction of external
      signals by integrins. Like other adapters, ADAP is a multifunctional protein and
      interacts with molecules such as Fyn, Slp-76, Ena/VASP proteins, Vav1, WASP and
      the Arp2/3 complex.

PMID- 11973130
TI  - Protein kinase C-theta;: signaling from the center of the T-cell synapse.
AB  - The hypothesis that protein kinase C (PKC)-theta; plays an important role in T
      lymphocyte activation, as indicated by numerous studies in cell lines, was
      recently confirmed in mice deficient in the expression of this enzyme. In
      response to TCR stimulation, peripheral T cells lacking PKC-theta; failed to
      activate NF-kappaB and AP-1, and to express IL-2. This revealed a critical
      function for this PKC family member in linking membrane-proximal activation
      cascades to transcriptional responses governing T-cell activation. Although the
      molecular interactions in which PKC-theta; engages have not been fully
      delineated, insights from a variety of recent studies have permitted new models
      to be formulated regarding the mechanisms through which it achieves its unique
      effector functions.

PMID- 11973131
TI  - New insights into the regulation and functions of Tec family tyrosine kinases in
      the immune system.
AB  - The Tec family of protein tyrosine kinases play an important role in signaling
      through antigen-receptors such as the TCR, BCR and Fcepsilon receptor. Recent
      studies have generated new insights into the domains in Tec kinases that take
      part in intramolecular and intermolecular binding. Furthermore, the consequences
      of these domain interactions for Tec activation and downregulation have been
      better defined. Genetic studies of kinase-knockout mice have emphasized the
      importance of Tec kinases in lymphocyte development, differentiation and
      apoptosis.

PMID- 11973132
TI  - Regulation of B cell fates by BCR signaling components.
AB  - Recent results obtained in mice harboring cytoplasmic mutations of Igalpha and/or
      Igbeta have reinforced the concept that the strength of BCR signaling is
      important for ensuring appropriate developmental outcomes as well as antigen
      specific responses. To establish the optimal signaling intensity and duration,
      the BCR utilizes positive and negative regulatory molecules. Studies are
      beginning to reveal how these molecules maintain immunological homeostasis and
      tolerance.

PMID- 11973133
TI  - Homeostasis of naive, effector and memory CD8 T cells.
AB  - Homeostatic control of CD8 T cell populations is essential for defense against
      infectious pathogens. Our understanding of the mechanisms that control naive,
      effector and memory T cell populations in the intact animal has increased
      significantly over the last several years. There have been some surprises. For
      example, peripheral tissues have been found to harbor unexpectedly large numbers
      of effector memory T cells. Also unexpected was the finding of programmed T cell
      proliferation following very brief exposure to antigen. These and other recent
      advances are summarized in the following review.

PMID- 11973134
TI  - Molecular mechanisms of activated T cell death in vivo.
AB  - The culmination of the immune response involves the death of the majority of the
      activated antigen-specific T lymphocytes. The death of these cells is important
      to prevent autoimmunity, to decrease the metabolic cost to the organism and to
      ensure T cell homeostasis. This review will focus on the mechanisms that, in
      animals, control the death of these activated cells. At least two separate types
      of cell death can occur (activation-induced cell death and activated T cell
      autonomous death) via death receptors such as Fas or the Bcl-2 related protein
      Bim, respectively. Finally, adjuvants that enable T cell survival may operate via
      NF-kappaB and Bcl-3 rather than cytokines.

PMID- 11973135
TI  - Influence of effector molecules on the CD8(+) T cell response to infection.
AB  - Expansion and contraction of antigen-specific CD8(+) T cells after infection or
      vaccination results in stable memory. Recent evidence demonstrates that anti
      microbial effector molecules such as perforin and IFN-gamma regulate specific
      aspects of CD8(+) T cell homeostasis by mechanisms that may be dependent or
      independent of pathogen clearance.

PMID- 11973136
TI  - T helper cell differentiation: on again, off again.
AB  - Recent studies raise the possibility that T helper (Th) polarization may be
      attributable to generalized activation and regulated silencing rather than
      regulated activation of target cytokine genes. The binding of transcription
      factors GATA-3 or T-bet to specific enhancers does recruit transcription factors
      such as NFAT-1 to IL-4 or IFNgamma promoters, respectively; however, GATA-3 also
      intrinsically suppresses T-bet and vice versa. Silencing of GATA-3/T-bet, which
      is influenced by factors such as cytokines, is associated with irreversible Th
      polarization. For the first few divisions (perhaps reflecting the situation in
      lymph nodes), naive Th cells retain pluripotency; after further cell divisions
      (perhaps under the influence of an inflammatory cytokine milieu) they may become
      polarized appropriately to respond to the specific environment.

PMID- 11973137
TI  - Interferon-producing cells: on the front line in immune responses against
      pathogens.
AB  - Interferon-producing cells (IPC) constitute a small population of leukocytes that
      secrete high levels of type I interferons in response to viruses. Although human
      IPC have been known for almost two decades, murine IPC have been identified only
      recently. Furthermore, it has been shown that IPC correspond to the enigmatic
      'plasmacytoid cells' identified in human lymph nodes during infections. These
      breakthroughs have brought IPC to the attention of immunologists for their role
      in innate immunity and in shaping T cell responses. Here we review recent
      progress and outstanding questions in the field.

PMID- 11973138
TI  - Control of adaptive immune responses by Toll-like receptors.
AB  - Recently, there has been considerable interest in how adaptive immune responses
      are controlled by the innate immune system. In particular, researchers have
      focused on how the differentiation of CD4 T cells is directed upon priming by
      dendritic cells. The identification of the Toll-like receptors as a family of
      pattern-recognition receptors involved in controlling dendritic cell activation
      has focused attention on these receptors as possible regulators of adaptive
      immune responses. However, recent studies have suggested that Toll-like receptors
      may only control the induction of Th1 responses and that a separate system of
      recognition regulates Th2 responses.

PMID- 11973139
TI  - The right place at the right time: novel B7 family members regulate effector T
      cell responses.
AB  - Recent identification of novel members of the B7-family of costimulatory ligands
      has illustrated their importance for costimulation, not only for initiation of
      adaptive immune responses, but also for regulation of activated effector
      lymphocytes. Two key features that distinguish these novel molecules from
      classical B7.1 and B7.2 costimulatory ligands are their broader expression in non
      lymphoid tissues and their binding to receptors induced on activated T cells.
      Whereas B7.1/B7.2-CD28 interactions are important for priming naive T cells,
      novel costimulatory interactions appear critical in regulating effector
      lymphocytes at sites of infection in the periphery.

PMID- 11973140
TI  - Negative co-receptors on lymphocytes.
AB  - The past year has seen significant advances in our understanding of critical
      roles of negative immunoregulatory signals delivered through the B7-CD28
      superfamily in regulating T cell activation and tolerance. Structural data on
      CTLA-4 have provided novel insights into the inhibitory functions of CTLA-4.
      Initial characterization of the PD-1-PD-1-ligand pathway has revealed that this
      pathway can downregulate TCR- and CD28-mediated signals. Recent studies indicate
      that ICOS exerts distinct effects at different phases of an immune response: ICOS
      can inhibit as well as stimulate T cell responses.

PMID- 11973141
TI  - Tsg101: HIV-1's ticket to ride.
AB  - Recent studies implicate the vacuolar protein-sorting pathway in the transport of
      the retroviral structural precursor (Gag) protein to its budding site on the
      plasma membrane of infected cells. This exploitation of the cellular endocytic
      trafficking machinery to release viral particles could lead to the identification
      of virus-specific modulators and provide opportunities to design new targeted
      anti-viral agents.

PMID- 11973142
TI  - Anchorless adhesins and invasins of Gram-positive bacteria: a new class of
      virulence factors.
AB  - Bacterial adherence to and invasion of eukaryotic cells are important mechanisms
      of pathogenicity. Most Gram-positive bacteria interact with the components of the
      host extracellular matrix (ECM) to adhere to, colonize and invade cells and
      tissues. The bacterial proteins that bind to components of the ECM harbour signal
      sequences for their secretion and mechanisms of anchoring to the host cell
      surface. However, in recent years, some cell-surface adhesins and invasins of
      Gram-positive bacteria have been described that do not possess a signal sequence
      or a membrane anchor. These proteins are secreted by an as-yet-unknown mechanism
      and are probably localized on the bacterial surface by reassociation. These
      anchorless but surface-located adhesins and invasins represent a new class of
      virulence factors.

PMID- 11973144
TI  - The ESAT-6/WXG100 superfamily -- and a new Gram-positive secretion system?
AB  - ESAT-6 is a small secreted protein of unknown function from Mycobacterium
      tuberculosis that is of fundamental importance in virulence and protective
      immunity. A PSI-BLAST search has identified distant homologues of ESAT-6 in more
      tractable bacteria, including Bacillus subtilis, Bacillus anthracis,
      Staphylococcus aureus and Clostridium acetobutylicum. The genes for ESAT-6-like
      proteins often cluster with genes encoding homologues of B. subtilis YukA. I
      speculate that the ESAT-6-like and YukA-like proteins form a novel Gram-positive
      secretion system potentially driven by the FtsK/SpoIIIE ATPase domains in the
      YukA-like proteins. The way is now open to investigate this hypothesis in
      organisms that are easier to manipulate than pathogenic mycobacteria.

PMID- 11973151
TI  - The compartment buffered by the urease of Helicobacter pylori: cytoplasm or
      periplasm?

PMID- 11973153
TI  - The importance of complete genome sequences.

PMID- 11973155
TI  - IFN-gamma and NO in mycobacterial disease: new jobs for old hands.
AB  - Granulomatous disease following exposure to Mycobacterium tuberculosis,
      Mycobacterium leprae or Mycobacterium avium is correlated with strong
      inflammatory and protective responses. The mouse model of mycobacterial infection
      provides an excellent tool with which to examine the inter-relationship between
      protective cell-mediated immunity and tissue-damaging hypersensitivity. It is
      well established that T cells and interferon (IFN)-gamma are necessary components
      of anti-bacterial protection. We propose that IFN-gamma also modulates the local
      cellular response by downregulating lymphocyte activation and by driving T cells
      into apoptosis, and that the events that limit excessive inflammation are largely
      mediated by IFN-gamma-induced nitric oxide (NO). In several murine models of
      mycobacterial infection, the absence of IFN-gamma and/or NO results in
      dysregulated granuloma formation and increased lymphocytic responses, which, in
      the case of M. avium infection, even leads to reduced bacterial growth.

PMID- 11973156
TI  - How do extracellular pathogens cross the blood-brain barrier?
AB  - Bacterial invasion of the meninges can occur as a consequence of bloodstream
      invasion by some bacterial pathogens. Bacteria enter the central nervous system
      following a direct interaction with the luminal side of the cerebral endothelium,
      which constitutes the blood-brain barrier. To breach the barriers protecting the
      brain, extracellular pathogens must cross a monolayer of tight junction
      expressing endothelial or epithelial cells. The limited number of pathogens
      capable of crossing these tight barriers and invading the meninges suggests that
      they display very specific attributes. For Neisseria meningitidis, type IV pili
      have been identified as being essential for meningeal invasion and it is believed
      other, as-yet-unidentified factors are also involved.

PMID- 11973157
TI  - Bacterial avoidance of phagocytosis.
AB  - Phagocytosis constitutes the primary line of host innate and adaptive defence
      against incoming microbial pathogens, providing an efficient means for their
      removal and destruction. However, several virulent bacteria that do not function
      as intracellular pathogens have evolved mechanisms to avoid and prevent
      phagocytosis that constitute an essential part of their pathogenic capacity. Some
      of these mechanisms include preventing recognition by phagocytic receptors or
      blocking uptake by professional phagocytes. Recently, the molecular mechanisms of
      such antiphagocytic properties have been elucidated for some pathogens. Such
      mechanisms illustrate the diversity of mechanisms bacterial pathogens use to
      avoid phagocytic uptake.

PMID- 11973158
TI  - Surface proteins and the pathogenic potential of Listeria monocytogenes.
AB  - On the basis of the recently determined genome sequence of Listeria
      monocytogenes, we performed a global analysis of the surface-protein-encoding
      genes. Only proteins displaying a signal peptide were taken into account. Forty
      one genes encoding LPXTG proteins, including the previously known internalin gene
      family, were detected. Several genes encoding proteins that, like InlB and Ami,
      possess GW modules that attach them to lipoteichoic acids were also identified.
      Additionally, the completed genome sequence revealed genes encoding proteins
      potentially anchored in the cell membrane by a hydrophobic tail as well as genes
      encoding P60-like proteins and lipoproteins. We describe these families and
      discuss their putative implications for host-pathogen interactions.

PMID- 11973159
TI  - The PE multigene family: a 'molecular mantra' for mycobacteria.
AB  - The PE multigene family of Mycobacterium tuberculosis is remarkable in that it is
      composed of approximately 100 highly homologous genes that are found only in
      mycobacteria. Early evidence suggests that proteins encoded by certain members of
      this gene family could be present in the mycobacterial cell wall, impact antigen
      presentation pathways and the ensuing host immune responses, and also provide a
      mechanism for generating antigenic diversity in mycobacteria.

PMID- 11973162
TI  - Self-determination is not an appropriate model for understanding parental
      permission and child assent.

PMID- 11973163
TI  - ACC/AHA Guideline Update for Perioperative Cardiovascular Evaluation for
      Noncardiac Surgery--Executive Summary. A report of the American College of
      Cardiology/American Heart Association Task Force on Practice Guidelines
      (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular
      Evaluation for Noncardiac Surgery).

PMID- 11973164
TI  - The use of and preferences for the transesophageal echocardiogram and pulmonary
      artery catheter among cardiovascular anesthesiologists.
AB  - The pulmonary artery catheter (PAC), although widely used in anesthesia for
      cardiac and vascular surgery, remains controversial. Use of transesophageal
      echocardiography (TEE) by cardiovascular anesthesiologists may be a substitute or
      a preference compared with the PAC, but this has been incompletely investigated.
      An anonymous, cross-sectional survey was mailed to anesthesiologists in Canada
      and the United States. Anesthesiologists described their use of the PAC and TEE
      during cardiac and vascular surgery, along with their demographic
      characteristics. Two hundred sixty-five (77%) of 345 anesthesiologists responded.
      All had the PAC available for use, and 56% had TEE available. Only 23 (11%
      overall) reported having undergone echocardiography training, half of whom had
      completed fellowships. Both the PAC and TEE were more often used in cardiac
      valvular surgery (P = 0.0001) than in aortocoronary bypass or abdominal vascular
      surgery. Among all anesthesiologists, the PAC remained the preferred monitor in
      either cardiac or vascular surgery (P = 0.0001), although many indicated a
      preference for neither monitor. Among anesthesiologists with echocardiography
      training, TEE was preferred (P = 0.0004). We found that TEE was accessible to
      more than half of the surveyed anesthesiologists in cardiovascular surgery, but
      relatively few of them had completed formal training in its use. Only those with
      completed formal TEE training indicated a significant preference for TEE use and
      also used it frequently. Given the continuing controversy about the appropriate
      application of the PAC, concern about the appropriate application of TEE is
      prudent. The PAC remains the more frequently used and preferred monitor among
      cardiovascular anesthesiologists. IMPLICATIONS: A survey of anesthesiologists
      found that pulmonary artery catheter monitoring is currently more frequently used
      compared with transesophageal echocardiography during cardiac and vascular
      surgery.

PMID- 11973165
TI  - The association of complication type with mortality and prolonged stay after
      cardiac surgery with cardiopulmonary bypass.
AB  - Outcome after cardiac surgery varies depending on complication type. We therefore
      sought to determine the association between complication type, mortality, and
      length of stay in a large series of patients undergoing cardiac surgery with
      cardiopulmonary bypass (CPB). Multivariate logistic regression was used to test
      for differences between complication types in mortality and prolonged length of
      stay (>10 days) while controlling for preoperative and intraoperative risk
      factors. In 2609 consecutive cardiac surgical patients requiring CPB, the
      mortality rate was 3.6%; 36.5% had one or more complications, and 15.7%
      experienced an adverse outcome (death or prolonged length of stay). Multivariate
      logistic regression demonstrated that complication type was significantly
      associated with adverse outcome (P < 0.001) independent of Parsonnet score and
      CPB time (c-index = 0.80). The development of noncardiac complications only
      (Group NC) and cardiac complications with other organ involvement (Group B)
      significantly increased mortality and hospital and intensive care unit length of
      stay (P < 0.001) when compared with cardiac complications only (Group C). The
      incidences of adverse outcome in Groups C, NC, and B were 15%, 43%, and 67%,
      respectively; the mortality rates were 3%, 7%, and 20%, respectively. All these
      intergroup comparisons were significantly different (adjusted P < 0.05).
      Complications involving organs other than the heart appear to be more deleterious
      than cardiac complications alone, underscoring the need for strategies to reduce
      noncardiac complications. IMPLICATIONS: Complications, particularly when they
      involve organs other than just the heart, increase mortality and prolong the
      length of hospital stay after heart surgery, independent of a patient's
      preoperative risk factors and the duration of cardiopulmonary bypass. Strategies
      aimed at preventing damage to other organs during cardiac surgery need to be
      improved.

PMID- 11973166
TI  - Isolated systolic hypertension is associated with adverse outcomes from coronary
      artery bypass grafting surgery.
AB  - Isolated systolic blood pressure has not been sufficiently studied in the
      perioperative setting and may contribute to morbidity and mortality after
      coronary artery bypass grafting (CABG) surgery. Our objective was to determine
      the prevalence of isolated systolic hypertension among patients who had CABG
      surgery and to assess whether isolated systolic hypertension is associated with
      perioperative and postoperative in-hospital morbidity or mortality. Patients who
      underwent CABG were selected from a prospective epidemiological study involving
      2417 patients in 24 medical centers. Patients were classified as having normal
      preoperative blood pressure, isolated systolic hypertension (systolic blood
      pressure >140 mm Hg), diastolic hypertension (diastolic blood pressure >90 mm
      Hg), or a combination of these. Demographic risk factors (age, sex, and
      ethnicity), clinical risk factors (diabetes mellitus, increased cholesterol,
      antihypertensive medications, history of congestive heart failure, myocardial
      infarction, hypertension, and neurological deficits), and behavioral risk factors
      (smoking and heavy drinking) were controlled for statistically. Adverse outcomes
      included left ventricular dysfunction, cerebral vascular dysfunction or events,
      renal insufficiency or failure, and all-cause mortality. Isolated systolic
      hypertension was found in 29.6% of patients. Unadjusted isolated systolic
      hypertension was associated with a 40% increased risk of adverse outcomes (odds
      ratio, 1.4; confidence interval, 1.1-1.7). After adjusting for other potential
      risk factors, the increased risk of adverse outcomes with isolated systolic
      hypertension was 30%. We conclude that isolated systolic hypertension is
      associated with a 40% increase in the likelihood of cardiovascular morbidity
      perioperatively in CABG patients. This increase remains present regardless of
      antihypertensive medications, anesthetic techniques, and other perioperative
      cardiovascular risk factors (e.g., age older than 60 yr or history of congestive
      heart failure, myocardial infarction, or diabetes). IMPLICATIONS: Isolated
      systolic hypertension is associated with a 40% increase in the likelihood of
      perioperative cardiovascular morbidity in coronary artery surgery patients.

PMID- 11973167
TI  - Perioperative melatonin secretion in patients undergoing coronary artery bypass
      grafting.
AB  - Melatonin, a neurohormone, plays an important role in adjusting the "biological
      clock" in humans. We sought to describe perioperative patterns of melatonin
      secretion in patients undergoing coronary artery bypass grafting surgery with
      cardiopulmonary bypass (CPB). After IRB approval and written informed consent, 12
      male patients scheduled for elective coronary artery bypass grafting under
      hypothermic CPB were enrolled in the study. During anesthesia, patients' eyes
      were carefully covered to prevent light effects. Blood samples were taken at
      specific time points during surgery, every 3 h in the immediate postoperative
      period, and for 24 h from 6:00 PM of Postoperative Day 2 until 6:00 PM of
      Postoperative Day 3. Plasma melatonin and cortisol concentrations were measured
      by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. During
      surgery, plasma melatonin concentrations were below the minimum sensitivity
      concentration, yet small concentrations, without circadian variation, were
      detected during the immediate postoperative period. During Postoperative Days 2
      and 3, circadian secretion patterns of melatonin were present in 10 patients and
      showed an inverse correlation with light intensity (r = 0.480; P < 0.01). Plasma
      cortisol concentrations in the immediate postoperative period were significantly
      larger than those before the induction of anesthesia (P < 0.01). Only three
      patients regained circadian secretion of cortisol. We concluded that melatonin
      and cortisol secretion was disrupted during cardiac surgery with CPB and in the
      immediate postoperative period. However, circadian rhythms of melatonin were
      present in most patients from Postoperative Day 2. Only 30% of the patients
      regained circadian rhythm of cortisol secretion. IMPLICATIONS: Melatonin is a
      hormone that plays an important role in adjusting the biological clock in humans
      and that regulates secretion of various other hormones. We studied melatonin
      secretion in patients undergoing cardiac surgery with cardiopulmonary bypass.
      Melatonin secretion was disturbed during and immediately after surgery but had
      recovered a circadian rhythm 24 h later, raising the question of whether
      melatonin should be supplemented before cardiac surgery.

PMID- 11973168
TI  - Mitral Doppler indices are superior to two-dimensional echocardiographic and
      hemodynamic variables in predicting responsiveness of cardiac output to a rapid
      intravenous infusion of colloid.
AB  - We hypothesized that mitral flow (MF) Doppler measurements could be used to
      predict cardiac output (CO) responsiveness to fluid challenge. Fourteen patients
      with normal systolic and diastolic function, scheduled for coronary artery bypass
      graft surgery, were evaluated as part of a pilot study in which preload was
      varied immediately before the beginning of cardiopulmonary bypass. A Validation
      group of 36 patients with different levels of systolic and diastolic function
      received a rapid infusion of 500 mL of 10% pentastarch. By use of transesophageal
      echocardiography, we measured left ventricular end-diastolic area, pulsed Doppler
      indices of the MF and pulmonary venous flow, and standard hemodynamic variables
      during acute volemic variations. A baseline measurement was first recorded,
      followed by measurements taken after a decrease (211 +/- 87 mL) and then an
      increase (176 +/- 149 mL) in preload (pilot study) and before and after 500 mL of
      pentastarch (validation study). In the pilot study, we found that a low
      velocity/time integral (VTI) E wave/A wave (E/A) ratio was associated with a
      larger increase in CO secondary to an increase in preload (r = 0.64, P < 0.05).
      Stepwise linear regression identified Doppler measurements of the mitral VTI E/A
      ratio as the most important variable to predict the increase in CO after fluid
      infusion. In the validation study, a mitral E/A ratio <1.26 before fluid infusion
      best predicted a 20% increase in stroke volume (receiver operating characteristic
      curve, 71%; P < 0.05), whereas no other hemodynamic or echocardiographic variable
      predicted preload responsiveness. We conclude that the MF Doppler filling pattern
      is an important factor to predict the increase in CO after intravascular fluid
      challenge in patients undergoing coronary artery bypass grafting. IMPLICATIONS:
      In the presence of low cardiac output, the clinician's ability to identify which
      patients are more likely to benefit from volume administration to improve
      hemodynamic status while avoiding fluid overload is important. The analysis of
      Doppler measurement of the mitral flow as an indirect indicator of the individual
      diastolic pressure/volume relationship may be useful to predict the intravascular
      volume responsiveness in patients undergoing coronary artery bypass graft
      surgery.

PMID- 11973169
TI  - The hemodynamic effects of rapacuronium in patients with coronary artery disease:
      succinylcholine and vecuronium compared.
AB  - Rapacuronium is a nondepolarizing muscle relaxant similar in structure to
      pancuronium, rocuronium, and vecuronium. Rapacuronium has a mild to moderate
      effect on heart rate and arterial blood pressure in ASA physical status I and II
      patients. However, rapacuronium was often administered after, e.g., thiopental,
      an inhaled anesthetic, and fentanyl, thus modifying or masking the hemodynamic
      effects of rapacuronium. In this study, we investigated the hemodynamic effects
      of rapacuronium and compared its effects with those of vecuronium and
      succinylcholine. Sixty patients scheduled to undergo routine coronary artery
      bypass grafting were selected to receive rapacuronium 1.5 mg/kg, vecuronium 0.1
      mg/kg, or succinylcholine 1 mg/kg. Heart rate, blood pressure, pulmonary artery
      pressures, and cardiac index were measured at 30- and 60-s intervals during the 2
      min after the induction of anesthesia with diazepam and for a 3-min period after
      study drug administration. The Rapacuronium group exhibited significantly larger
      decreases in blood pressure and systemic vascular resistance than the Vecuronium
      or Succinylcholine groups. One patient in the Rapacuronium group experienced
      cutaneous flushing associated with a 33% decrease in blood pressure.
      IMPLICATIONS: Rapacuronium is associated with a significantly larger decrease in
      blood pressure than succinylcholine or vecuronium, and this decrease should be
      considered when using rapacuronium in patients who cannot tolerate this decrease.

PMID- 11973170
TI  - Pulmonary gas exchange in coronary artery surgery patients during sevoflurane and
      isoflurane anesthesia.
AB  - As the surgical population ages, the number of patients presenting with coronary
      artery disease and age-related loss of pulmonary recoil will increase. Although
      their influence on gas exchange in this population remains unknown, sevoflurane
      and isoflurane are used for an increasing variety of surgical procedures. We
      examined pulmonary gas exchange (multiple inert gas elimination technique) in 30
      patients presenting for coronary artery bypass grafting. After a baseline
      measurement taken during midazolam anesthesia, patients were continued on
      sevoflurane (n = 10), isoflurane (n = 10), or midazolam (n = 10) for 20 min, then
      a second measurement was taken. During sevoflurane and isoflurane anesthesia,
      blood flow to lung areas with a low ventilation/perfusion ratio (Va/Q) was
      significantly increased in comparison with control. During sevoflurane
      anesthesia, blood flow to lung areas with a normal Va/Q ratio (76 +/- 12 versus
      control: 89 +/- 5, mean +/- SD) and PaO(2) (138 +/- 31 versus control: 156 +/- 35
      mm Hg, mean +/- SD) were depressed, whereas an increase in Va/Q-dispersion (log
      SD(Q)) was observed during isoflurane anesthesia. We conclude that both
      sevoflurane and isoflurane alter the distribution of perfusion in the lung, but
      only sevoflurane significantly depresses PaO(2). IMPLICATIONS: Both sevoflurane
      and isoflurane modified pulmonary blood flow in patients with coronary artery
      disease, but only sevoflurane depresses arterial oxygenation in this population.

PMID- 11973171
TI  - Insulin increases neutrophil count and phagocytic capacity after cardiac surgery.
AB  - We previously reported that a continuous insulin infusion improves neutrophil
      phagocytic function after cardiac surgery in diabetic patients. These data
      suggested that hyperglycemia impairs neutrophil function, and because nondiabetic
      patients also experience hyperglycemia during cardiac surgery, we hypothesized
      that a continuous insulin infusion would improve glucose control and neutrophil
      function in nondiabetic cardiac surgical patients. Patients were randomized to
      receive either no insulin (Control group) or a continuous insulin infusion
      (Insulin group), with glucose measurements every 10 min during cardiopulmonary
      bypass (CPB). Blood glucose was significantly lower in the Insulin group
      immediately after surgery but not during surgery. When assessed as the percentage
      of phagocytic cells, neutrophil function was similar in the Control and Insulin
      groups at baseline (55% and 57%, respectively) and after CPB (38% and 43%,
      respectively). However, a quantitative determination of neutrophil phagocytic
      activity showed that whole blood neutrophil phagocytic capacity increased
      significantly in both groups at 60 min after CPB when compared with their
      respective baseline values and that the increase in total neutrophil phagocytic
      capacity was significantly more in the Insulin group compared with the Control
      group (P = 0.036). This observation was primarily due to a larger increase in the
      peripheral blood neutrophil count and not to increased activation of neutrophils.
      IMPLICATIONS: IV insulin, as used in this study, had effects on blood glucose
      only after cardiac surgery, when it was associated with an increased neutrophil
      count and a greater total capacity of peripheral blood neutrophils to ingest
      foreign particles.

PMID- 11973172
TI  - The effects of acute normovolemic hemodilution on left ventricular systolic and
      diastolic function in the absence or presence of beta-adrenergic blockade in
      dogs.
AB  - Acute normovolemic hemodilution (ANH) increases cardiac output because of a
      reduction in blood viscosity and enhancement of left ventricular (LV)
      contractility. The status of LV function, especially LV diastolic function during
      ANH, remains controversial. We therefore examined LV systolic and diastolic
      function during ANH. Sixteen dogs were anesthetized with isoflurane in the
      absence (Group 1) and presence (Group 2) of beta-adrenergic blockade (propranolol
      1 mg/kg). LV contractility was quantified by the slope (M(w)) of the stroke work
      and end-diastolic volume relation. Diastolic function was evaluated with the time
      constant of LV relaxation (T), chamber stiffness constant (K(c)), peak LV
      diastolic filling rate during early filling (peak E) and atrial contraction (peak
      A), and ratio of peak E to peak A (E/A). Normovolemic exchange of blood (50
      mL/kg) for 6% hydroxyethyl starch (ANH50) significantly increased M(w) in Group 1
      but not in Group 2. In both groups, ANH50 significantly decreased T. ANH50
      significantly increased peak E in both groups and peak A in Group 1, and it did
      not change the E/A ratio or K(c) in either group. ANH causes positive inotropic
      effects and enhances diastolic function without beta-blockade. Even after beta
      adrenergic blockade, ANH improves diastolic function through the reduction of LV
      ejection impedance. IMPLICATIONS: Acute normovolemic hemodilution enhances LV
      (left ventricular) diastolic function by alterations in the LV loading condition
      produced by hemodilution, which mainly contributes to a compensatory increase in
      cardiac output.

PMID- 11973173
TI  - Fibrinolysis during liver transplantation is enhanced by using solvent/detergent
      virus-inactivated plasma (ESDEP).
AB  - After the introduction of solvent/detergent-treated plasma (ESDEP) in our
      hospital, an increased incidence of hyperfibrinolysis was observed (75% vs 29%; P
      = 0.005) compared with the use of fresh frozen plasma for liver transplantation.
      To clarify this increased incidence, intraoperative plasma samples of patients
      treated with fresh frozen plasma or ESDEP were analyzed in a retrospective
      observational study. During the anhepatic phase, plasma levels of D-dimer (6.58
      vs 1.53 microg/mL; P = 0.02) and fibrinogen degradation products (60 vs 23 mg/L;
      P = 0.018) were significantly higher in patients treated with ESDEP. After
      reperfusion, differences increased to 23.5 vs 4.7 microg/mL (D-dimer, P = 0.002)
      and 161 vs 57 mg/L (fibrinogen degradation products, P = 0.001). The amount of
      plasma received per packed red blood cell concentrate, clotting tests, and levels
      of individual clotting factors did not show significant differences between the
      groups. alpha(2)-Antiplasmin levels, however, were significantly lower in
      patients receiving ESDEP during the anhepatic phase (0.37 vs 0.65 IU/mL; P <
      0.001) and after reperfusion (0.27 vs 0.58 IU/mL; P = 0.001). Analysis of
      alpha(2)-antiplasmin levels in ESDEP alone showed a reduction to 0.28 IU/mL
      (normal >0.95 IU/mL) because of the solvent/detergent process. Therapeutic
      consequences for the use of ESDEP in orthotopic liver transplantation are
      discussed in view of an increased incidence of hyperfibrinolysis caused by
      reduced levels of alpha(2)-antiplasmin in the solvent/detergent-treated plasma.
      IMPLICATIONS: The use of solvent/detergent virus-inactivated plasma is of
      increasing importance in the prevention of human immunodeficiency virus and
      hepatitis C virus transmission. Since the use of this plasma during orthotopic
      liver transplantation has increased, the incidence of hyperfibrinolysis was
      observed. Clotting analysis of the patients revealed small alpha(2)-antiplasmin
      concentrations because of the solvent/detergent process.

PMID- 11973174
TI  - The effects of advanced age on the incidence of supraventricular arrhythmias
      after pneumonectomy in dogs.
AB  - Because advanced age is the strongest independent risk factor for the development
      of supraventricular arrhythmias after lung resection, we compared the incidence
      and premorbid events of supraventricular arrhythmias after pneumonectomy in young
      and elderly dogs with the aim of better understanding potential age-related
      arrhythmogenic mechanisms. Right pneumonectomy was performed in 15 male mongrel
      dogs ("old" > or =8 yr [n = 8], "young" <4 yr [n = 7]) and the electrocardiogram
      continuously recorded by an implantable telemetry system for 1 wk before
      euthanizing. After surgery, 7 of 8 older animals (88%) developed a total of 23
      episodes of sustained (>30 s) paroxysmal supraventricular tachycardia (SVT),
      compared with 0 of 7 (0%) young dogs, P = 0.0014. Analysis of heart rate over the
      60 min preceding the onset of SVT revealed a progressive increase in sinus rhythm
      beginning 15 min before the arrhythmia. Comparison of the heart rate and rhythm
      obtained in younger animals from the corresponding postoperative hour
      demonstrated that although older animals developed more atrial (P = 0.03) and
      ventricular premature contractions (P = 0.056) and episodes of nonsustained
      ventricular tachycardia (P = 0.01), heart rate was similar for both groups until
      the increase in elderly dogs preceding the onset of SVT. Histologic examination
      of the atria showed interstitial fibrosis in old but not young animals. In
      addition, 4 of 8 (50%) elderly animals exhibited an inflammatory response within
      the atria consistent with acute myo- and epicarditis. We conclude that elderly
      dogs have an increased supraventricular arrhythmogenic potential within the first
      week after pneumonectomy than younger animals, perhaps because of increased
      atrial fibrosis and inflammation. Heart rate analysis before SVT onset suggests
      that adrenergic predominance was a probable responsible trigger. IMPLICATIONS: In
      this canine pneumonectomy model, advanced age was associated with an increased
      incidence of supraventricular arrhythmias, perhaps because of increased atrial
      fibrosis and inflammation.

PMID- 11973175
TI  - Vascular responsiveness to brachial artery infusions of phenylephrine during
      isoflurane and desflurane anesthesia.
AB  - Compared with equi-minimum alveolar anesthetic concentration (MAC) isoflurane,
      desflurane is associated with greater levels of sympathetic nerve activity in
      humans but similar reductions in blood pressure. To explore these divergent
      effects, we evaluated vascular alpha(1)-adrenoceptor responses in the human
      forearm during isoflurane and desflurane anesthesia to determine if alpha(1)
      adrenoceptor responses were more substantially attenuated during desflurane
      administration. Bilateral forearm venous occlusion plethysmography was used to
      examine arterial blood flow and to determine changes in forearm vascular
      resistance during brachial artery infusions of saline and phenylephrine (0.2,
      0.4, 0.8, and 1.6 microg/min) in 22 conscious subjects and during anesthesia with
      0.65 and 1.3 MAC isoflurane or desflurane. Infusion of phenylephrine into the
      brachial artery increased the forearm vascular resistance in a dose-dependent
      manner. The arterial response to phenylephrine was significantly attenuated by
      0.65 and 1.3 MAC desflurane and similarly attenuated during 1.3 MAC isoflurane (P
      < 0.05). Impaired arterial alpha(1)-adrenoceptor responsiveness occurred during
      desflurane. However, this effect was statistically similar (P > 0.05) to the
      impaired responses during isoflurane. Blood pressure decreases during volatile
      anesthesia may be, in part, caused by decreased alpha(1)-adrenoceptor
      responsiveness. IMPLICATIONS: alpha-receptors on blood vessels regulate
      constriction and dilation and therefore modulate blood pressure. This research
      indicates that vasoconstriction via the alpha(1)-receptor vascular response is
      impaired during isoflurane and desflurane anesthesia.

PMID- 11973176
TI  - Assessing errors in the determination of base excess.
AB  - We compared estimates for base excess of extracellular fluid (BE(ecf); mmol/L)
      obtained in five clinically used blood gas analyzers: AVL Compact 2 (Roche
      Diagnostics, Mannheim, Germany), Ciba-Corning 860 (Bayer Diagnostics, Fernwald,
      Germany), IL 1620 (Instrumentation Laboratories, Lexington, MA), Stat Profile
      Ultra (Nova Biomedical, Waltham, MA), and ABL 510 (Radiometer, Copenhagen,
      Denmark). A total of 134 measurements per analyzer were obtained in arterial and
      venous blood samples from 10 patients undergoing cardiac surgery and 65
      measurements per analyzer in venous blood samples from 2 healthy volunteers. The
      blood samples were equilibrated in a tonometer with gases of known composition
      (37 degrees C). Additional theoretical studies were performed to evaluate the
      relationship between pH and calculated BE(ecf) value (with varied PCO(2)) using
      the formulas of the various analyzers. The standard deviations of repeated
      measurements were 0.24 mmol/L for ABL 510 and approximately 0.45 mmol/L for the
      other 4 analyzers. The maximal systematic difference between the average of all
      measurements of each analyzer was 3.7 mmol/L; this was primarily attributable to
      differences in measuring pH, and, to a lesser extent, to differences in
      calculation and determination of PCO(2). Comparison of the results from samples
      with different oxygen saturation showed that the relative alkalinity of
      deoxygenated hemoglobin (Haldane effect) can also influence the determinations of
      BE(ecf). IMPLICATIONS: A clinically useful way to quantify nonrespiratory
      disturbances of the acid-base balance is calculation of the base excess of
      extracellular fluid by using blood gas analyzers. In this study, we found
      significant variability in estimates of base excess of extracellular fluid
      obtained with five analyzers from different manufacturers. This variability is
      attributable to multiple factors, including lack of correction for deoxygenated
      hemoglobin (Haldane effect).

PMID- 11973177
TI  - Massive hemorrhage during radiofrequency ablation of a pulmonary neoplasm.
AB  - IMPLICATIONS: Radiofrequency ablation is a new investigational therapy for
      primary and secondary neoplasms. In this article, the authors describe the
      anesthetic management of the radiofrequency ablation of a pulmonary neoplasm
      complicated by massive hemorrhage.

PMID- 11973178
TI  - Vasospasm after use of a tourniquet: another cause of postoperative limb
      ischemia?
AB  - IMPLICATIONS: Two previously reported causes of postoperative limb ischemia after
      use of a tourniquet, compartment syndrome and arterial thromboembolism, require
      aggressive and invasive management. We report another probable cause that can be
      managed nonsurgically: vasospasm.

PMID- 11973179
TI  - Permission and assent for clinical research in pediatric anesthesia.
AB  - IMPLICATIONS: This article discusses the process and specific nature of informed
      consent for clinical research in pediatric anesthesia. For informed consent to be
      meaningful, permission from the child's proxy must be obtained and the child's
      assent must be tailored in a manner that is sensitive to the abilities of
      children.

PMID- 11973180
TI  - Testing anal sphincter tone predicts the effectiveness of caudal analgesia in
      children.
AB  - In this study, we examined the effectiveness of caudal blocks and correlated it
      with the laxity of the patients' anal sphincter before emergence from anesthesia
      in 178 children undergoing inguinal and/or penile surgery. Bupivacaine 0.25% in a
      volume of 0.6-1.25 mL/kg was used in all patients. The presence of a lax anal
      sphincter at the end of surgery correlated significantly with the reduced
      administration of narcotics intraoperatively and in the postanesthesia care unit
      (P < 0.001). The sensitivity of the sphincter tone test was 98.1% with a 95%
      confidence interval (CI) ranging from 94.3% to 99.6%. The specificity of the test
      was 94.4% with a 95% CI of 72.0%-100%. The positive predictive value of this test
      in predicting adequate caudal block was excellent (99.4%) with a 95% CI of 96.1%
      100%. The negative predictive value was better than average (85%) with a 95% CI
      of 62.9%-95.4%. We conclude that a lax anal sphincter can predict the
      effectiveness of analgesia after pediatric caudal blockade. A tight sphincter may
      suggest the need to repeat the block before the child awakens, or consider
      alternate methods of postoperative analgesia. IMPLICATIONS: A lax anal sphincter
      in children undergoing inguinal and/or penile surgery can predict the
      effectiveness of analgesia after pediatric caudal blockade.

PMID- 11973181
TI  - The hemodynamic effects of pediatric caudal anesthesia assessed by esophageal
      Doppler.
AB  - Pediatric caudal anesthesia is an effective method with an infrequent
      complication rate. However, little is known about its cardiovascular
      consequences. Transesophageal Doppler, a noninvasive method, provides the
      opportunity for a reappraisal of the hemodynamic effects of this technique. After
      parental informed consent, we studied 10 children aged 2 mo to 5 yr who were
      scheduled for lower abdominal surgery. General anesthesia was induced using
      sevoflurane and was followed by the insertion of a transesophageal Doppler probe.
      Caudal anesthesia was performed using 1 mL/kg of 0.25% bupivacaine with 1/200,000
      epinephrine. Hemodynamic variables were collected before and after caudal
      anesthesia. No complications arose during insertion of the probe. The mean time
      between the two sets of measurements was 15 min. Heart rate, systolic, diastolic,
      and mean arterial blood pressures were not modified by caudal anesthesia.
      Descending aortic blood flow increased significantly from 1.14 to 1.92 L/min. (P
      = 0.0002). Aortic ejection volume increased from 8.5 to 14.5 mL (P = 0.0002).
      Aortic vascular resistances decreased from 6279 to 3901 dynes. s(-1) x m(-5) (P =
      0.005). Caudal anesthesia did not affect heart rate and mean arterial blood
      pressure but induced a significant increase in descending aortic blood flow.
      IMPLICATIONS: Although pediatric caudal anesthesia does not alter heart rate nor
      arterial blood pressure, significant changes occur in regional blood flow
      distribution. Descending aortic blood flow increases significantly after caudal
      anesthesia, whereas lower body vascular resistances decrease.

PMID- 11973182
TI  - Caudal clonidine prolongs analgesia from caudal S(+)-ketamine in children.
AB  - We performed a prospective randomized double-blinded study to test preservative
      free S(+)-ketamine alone or in combination with clonidine for intra- and
      postoperative caudal blockade in pediatric surgery over a 24-h period. Fifty
      three children (1-72 mo) scheduled for inguinal hernia repair were caudally
      injected with either S(+)-ketamine 1 mg/kg alone (Group K) or with additional
      clonidine (Group C1 = 1 microg/kg; Group C2 = 2 microg/kg) during sevoflurane
      anesthesia via a laryngeal mask. Intraoperative monitoring included heart rate,
      blood pressure, and pulse oximetry; postoperative monitoring included a pain
      discomfort scale and a sedation score. No additional analgesic drugs were
      required during surgery. The mean duration of postoperative analgesia was 13.3 +/
      9.2 h in Group K, 22.7 +/- 3.5 h in Group C1, and 21.8 +/- 5.2 h in Group C2 (P
      < 0.0001, Group K versus other groups). Groups C1 and C2 received significantly
      fewer analgesics in the postoperative period than Group K (15% and 18% vs 63%; P
      < 0.01). The three groups had similar postoperative sedation scores. We conclude
      that the combination of S(+)-ketamine 1 mg/kg with clonidine 1 or 2 microg/kg for
      caudal blockade in children provides excellent analgesia without side effects
      over a 24-h period. IMPLICATIONS: Caudally administered preservative-free S(+)
      ketamine combined with 1 or 2 microg/kg clonidine provides excellent
      perioperative analgesia in children and has minimal side effects.

PMID- 11973184
TI  - The effect of remifentanil or fentanyl on postoperative vomiting and pain in
      children undergoing strabismus surgery.
AB  - Postoperative vomiting (POV) after strabismus surgery in children results in
      discomfort and prolonged hospital stays. Opioids increase the incidence of POV.
      Remifentanil has a context-sensitive half-life of 3 to 4 min, and how this short
      half-life influences POV in those patients is unknown. We conducted a
      prospective, double-blinded study in 81 ASA status I or II children from 2 to 12
      yr of age undergoing elective strabismus surgery under general anesthesia.
      Patients were randomized to receive either remifentanil (bolus 1 microg/kg;
      infusion 0.1-0.2 microg x kg(-1) x min(-1)) or fentanyl (2 microg/kg, and 1
      microg/kg every 45 min). POV episodes were recorded for 25 h. Pain scores were
      obtained by using an objective pain scale for 60 min during recovery. The number
      of patients who experienced POV did not differ significantly between groups (49%
      vs 48%). However, in the Remifentanil group, POV episodes were significantly less
      frequent (0.95 vs 2.2 episodes). In contrast, fentanyl was associated with lower
      pain scores during the first 30 min of recovery. We conclude that children
      undergoing strabismus surgery under balanced anesthesia with remifentanil,
      compared with fentanyl, showed less frequent POV. However, early postoperative
      analgesia was better with fentanyl. IMPLICATIONS: Opioids increase the incidence
      of postoperative vomiting (POV). Remifentanil is characterized by the shortest
      half-life of all opioids used in anesthetic practice. Therefore, we studied the
      effect of remifentanil on POV compared with the longer-acting opioid fentanyl in
      children undergoing strabismus surgery.

PMID- 11973185
TI  - The effect of fentanyl on the emergence characteristics after desflurane or
      sevoflurane anesthesia in children.
AB  - Desflurane and sevoflurane anesthesia are associated with emergence agitation in
      children. In this study, we examined the effect of a single intraoperative dose
      of fentanyl on emergence characteristics in children undergoing adenoidectomy.
      One hundred children, 2-7 yr old, were randomly assigned to receive desflurane or
      sevoflurane for maintenance of general anesthesia after an inhaled induction with
      sevoflurane and a 2.5 microg/kg dose of fentanyl. An observer blind-ed to the
      anesthetic technique assessed the times to achieve emergence, extubation and
      recovery criteria, as well as emergence behaviors. The results showed a similar
      incidence of severe emergence agitation after general anesthesia with desflurane
      (24%) and sevoflurane (18%). Times to achieve extubation and postanesthesia care
      unit discharge criteria were shorter with desflurane than with sevoflurane. With
      this technique, desflurane allows for a more rapid emergence and recovery than
      sevoflurane. In children receiving desflurane or sevoflurane, the concurrent use
      of fentanyl in a dose of 2.5 microg/kg results in a small incidence of emergence
      agitation. IMPLICATIONS: The concurrent use of fentanyl in a dose of 2.5
      microg/kg in children receiving desflurane or sevoflurane results in a low
      incidence of emergence agitation. Desflurane allows for a more rapid emergence
      and recovery than sevoflurane.

PMID- 11973186
TI  - The effect of insufflation pressure on CO(2) pneumoperitoneum and embolism in
      piglets.
AB  - We conducted this study to investigate the effect of insufflation pressure on the
      pathophysiology of CO(2) pneumoperitoneum and embolism in an infant model. Twenty
      anesthetized piglets had stepwise intraperitoneal insufflation with CO(2) for 15
      min at pressures ranging from 5 to 20 mm Hg. The piglets were ventilated to
      baseline normocarbia (ETCO(2) = 30 mm Hg, PaCO(2) = 38 mm Hg) before beginning
      each insufflation. CO(2) was then insufflated IV in 15 of these piglets at the
      same pressures. There was no reduction of blood pressure or cardiac output with
      intraperitoneal insufflation, but the stroke volume declined significantly (*P <
      0.05) from (mean +/- SE) 10.6 +/- 1.3 mL to 8.5 +/- 1.3* mL and from 10.0 +/- 1.4
      mL to 7.2 +/- 1.2* mL at 15 and 20 mm Hg insufflation pressure, respectively.
      Abdominal insufflation at 5, 10, 15, and 20 mm Hg caused an increase in ETCO(2)
      to 31.7 +/- 0.8 mm Hg, 35.6 +/- 1.2* mm Hg, 37.5 +/- 1.5* mm Hg, and 40.1 +/-
      1.8* mm Hg and in PaCO(2) to 41.1 +/- 1.3* mm Hg, 44.2 +/- 1.4* mm Hg, 49.9 +/-
      1.8* mm Hg, and 53.0 +/- 2.1* mm Hg, respectively. In contrast, the
      ETCO(2)decreased to 19.4 +/- 1.5* mm Hg, 20.4 +/- 1.4 mm Hg, 15.2 +/- 2.1* mm Hg,
      and 10.6 +/- 2.0* mm Hg with IV insufflation using the same pressures. IV
      insufflation caused marked hypotension and mortality. As the insufflation
      pressure increased, the mortality increased (0 in 15, 1 in 15, 1 in 14, and 6 in
      13* at 5, 10, 15, and 20 mm Hg; *P < 0.05 vs 0 in 15, 1 in 15, and 1 in 14). This
      study suggests that although intraperitoneal insufflation up to 20 mm Hg may be
      tolerated hemodynamically, the lowest possible pressure should be used to reduce
      hypercarbia. A low insufflation pressure may also prevent mortality from CO(2)
      embolism. IMPLICATIONS: The lowest pressure possible should be used when
      inflating the abdomen with CO(2) to perform a laparoscopy in babies. A low
      pressure allows better ventilation and may prevent mortality if CO(2) is
      accidentally injected into a vein.

PMID- 11973187
TI  - The efficacy of premedication with celecoxib and acetaminophen in preventing pain
      after otolaryngologic surgery.
AB  - Non-opioid analgesics are often used to supplement opioids for the management of
      perioperative pain. In this randomized, double-blinded, placebo-controlled study,
      we examined the effects of acetaminophen and a cyclooxygenase type-2 inhibitor,
      celecoxib, when administered alone or in combination, before elective
      otolaryngologic surgery in 112 healthy outpatients. Subjects were assigned to 1
      of 4 study groups: Group 1, placebo (vitamin C, 500 mg per os [PO]); Group 2,
      acetaminophen 2000 mg PO; Group 3, celecoxib 200 mg PO; or Group 4, acetaminophen
      2000 mg and celecoxib 200 mg PO. All patients received a standardized anesthetic
      technique. During the postoperative period, pain was assessed using a 10-point
      verbal rating scale. Recovery times, the need for rescue analgesics, side
      effects, and patient satisfaction scores were also recorded. The combination of
      acetaminophen and celecoxib was significantly more effective than placebo in
      reducing postoperative pain. Celecoxib, when administered alone or in combination
      with acetaminophen, improved patients' satisfaction with their postoperative
      analgesia. With the combination of acetaminophen and celecoxib, an additional
      expenditure of $6.16 would be required to obtain complete satisfaction with
      postoperative pain management in one additional patient who would not have been
      completely satisfied if he/she had received the placebo. However, oral celecoxib
      or acetaminophen alone was not significantly more effective than placebo in
      reducing postoperative pain when administered before surgery. We conclude that
      oral premedication with a combination of acetaminophen (2000 mg) and celecoxib
      (200 mg) was highly effective in decreasing pain and improving patient
      satisfaction after outpatient surgery. IMPLICATIONS: Oral premedication with a
      combination of acetaminophen (2000 mg) and celecoxib (200 mg) was effective in
      decreasing pain and improving patient satisfaction after otolaryngologic surgery.
      However, acetaminophen (2000 mg) or celecoxib (200 mg) alone was not
      significantly more effective than placebo in reducing postoperative pain.

PMID- 11973188
TI  - Induction of anesthesia and insertion of a laryngeal mask airway in the prone
      position for minor surgery.
AB  - The use of the prone position for surgery presents potential obstacles to rapid
      tracking of patients during ambulatory anesthesia. We describe a prospective
      audit of 73 patients who placed themselves in the prone position; anesthesia was
      induced in this position and a laryngeal mask airway (LMA) was used to maintain
      the airway. Additional increments of propofol were given to one patient who had
      laryngospasm and to nine who required deepening of anesthesia before the LMA
      could be inserted. Of four cases with LMA malpositioning, the LMA was adjusted
      easily in three, but in one patient who was edentulous, it was necessary to hold
      the LMA for the duration of the procedure. Manual ventilation of the lungs via
      the LMA was required because of arterial oxygen desaturation and hypoventilation
      in four patients. Blood was noted outside the nostrils in two patients,
      presumably caused by soft tissue trauma after insertion of the LMA, and
      bradycardia occurred in five patients. In the postoperative period, hoarseness
      and sore throat were observed in one and six patients, respectively. With
      experience and appropriate patient selection, it is possible to induce and
      maintain anesthesia using a LMA in patients in the prone position for ambulatory
      surgery. IMPLICATIONS: With experience and appropriate patient selection, it is
      possible to induce and maintain anesthesia using a laryngeal mask airway in
      patients in the prone position for ambulatory surgery.

PMID- 11973189
TI  - Ondansetron orally disintegrating tablet versus placebo for the prevention of
      postdischarge nausea and vomiting after ambulatory surgery.
AB  - IMPLICATIONS: Ondansetron orally disintegrating tablet reduces postdischarge
      nausea and vomiting and improves patient satisfaction with postoperative nausea
      and vomiting management.

PMID- 11973190
TI  - Alpha-2 adrenoceptor activity affects propofol-induced sleep time.
AB  - alpha(2) Adrenoceptor activity is involved in the mechanism of anesthesia.
      Clonidine, a alpha(2) adrenoceptor agonist, and yohimbine, a alpha(2)
      adrenoceptor antagonist, increase and decrease barbiturate-induced sleep times.
      In this study, we examined the effects of these drugs on propofol-induced sleep
      time. One-hundred-eighteen male Wistar rats weighing 320-400 g were used. Rats
      received saline, yohimbine (1, 0.1, or 0 mg/kg), or clonidine (300, 30, 3, or 0
      microg/kg) intraperitoneally followed by 60 mg/kg of propofol in various
      combinations. In two series of experiments, either sleep time or prefrontal
      cortex norepinephrine release (microdialysis) was measured. One
      milligram/kilogram of yohimbine decreased propofol-induced sleep time to
      approximately 70% of control, and this was accompanied by an increase in
      perfusate norepinephrine of approximately 240% of control. Clonidine increased
      sleep time approximately 260% (300 microg/kg) and approximately 170% (30
      microg/kg), and this was accompanied by a decrease (approximately 60% in both
      doses) in perfusate norepinephrine. In the present study, we show that the
      alpha(2) antagonist, yohimbine, decreased and the alpha(2) agonist, clonidine,
      increased propofol-induced sleep times. These changes were essentially mirrored
      in both groups by changes in norepinephrine release in the prefrontal cortex.
      IMPLICATIONS: Central alpha(2) adrenoceptor is thought to be involved in several
      IV anesthetics-induced sleep. In this study, activation of the receptor increased
      the propofol-induced sleep time, whereas its inhibition decreased the sleep time.
      The results provide further evidence that the alpha(2) receptor is a good tool to
      elucidate the mechanism of anesthetics-induced sleep.

PMID- 11973191
TI  - Propofol anesthesia enhances the pressor response to intravenous ephedrine.
AB  - The induction of anesthesia with propofol is often associated with a decrease in
      arterial blood pressure (BP). Although vasopressors are sometimes required to
      reverse the propofol-induced hypotension, little is known about the effect of
      propofol on these drugs. We studied the effects of propofol and sevoflurane on
      pressor response to i.v. ephedrine. Thirty adult patients were randomly assigned
      to one of two groups. In the Propofol group (n = 15), patients received propofol
      2.5 mg/kg i.v. for induction followed by 100 microg x kg(-1) x min(-1) i.v. for
      maintenance. In the Sevoflurane group (n = 15), anesthesia was induced with
      sevoflurane 3%-4% in oxygen and maintained with sevoflurane 2% in oxygen. All
      patients in both groups received ephedrine 0.1 mg/kg i.v. before and after the
      anesthetic induction. Ephedrine increased the heart rate significantly (P < 0.05)
      in awake patients in both study groups. In contrast, there was no increase in
      heart rate after the ephedrine administration under propofol or sevoflurane
      anesthesia. In awake patients, transient increases in mean BP were observed after
      i.v. ephedrine in both groups. In the Propofol group, 2 min after the
      administration of ephedrine, mean BP increased 16% +/- 10% under anesthesia but
      increased only 4% +/- 6% when the same patients were awake. The magnitudes of the
      pressor responses to ephedrine during propofol anesthesia were significantly
      greater (P < 0.05) than during the awake state. However, ephedrine 0.1 mg/kg i.v.
      showed no significant increases in BP during sevoflurane anesthesia. We conclude
      that propofol, not sevoflurane, anesthesia augments the pressor responses to i.v.
      ephedrine. IMPLICATIONS: The effect of anesthetics on vasopressor-mediated
      cardiovascular effects is poorly understood. We evaluated the pressor response to
      ephedrine during propofol or sevoflurane anesthesia. Our study suggests that
      anesthesia-induced hypotension may be easier to reverse with ephedrine during
      propofol anesthesia than during sevoflurane anesthesia.

PMID- 11973192
TI  - Target-controlled versus manually-controlled infusion of propofol for direct
      laryngoscopy and bronchoscopy.
AB  - Few studies have compared the clinical profile of target-controlled infusions of
      propofol with that of manually-controlled infusions. Fifty-four ASA physical
      status I or II patients scheduled for an elective otorhinolaryngology endoscopy
      performed under general anesthesia with spontaneous ventilation were enrolled in
      this prospective randomized study to compare the clinical outcome of such
      administrations. Before induction, all patients received a single alfentanil
      bolus dose (10 microg/kg). Propofol administration was adapted to maintain
      absence of movement, hemodynamic stability, and efficient spontaneous
      ventilation. When compared with the Manually-Controlled Infusion group, in the
      Target-Controlled Infusion group there were fewer movements at insertion of the
      laryngoscope (14.8% vs. 44.4%), improved hemodynamic stability (largest
      variations of mean arterial blood pressure <10% of control values, versus 20%),
      fewer episodes of apnea, and less respiratory acidosis after endoscopy (pH = 7.37
      +/- 0.05 and PaCO(2) = 50 +/- 7 mm Hg versus pH = 7.28 +/- 0.06 and PaCO(2) = 58
      +/- 9 mm Hg); the recovery was also shorter (time to opening eyes or verbal
      response, 4.6 +/- 2.0 min and 6.8 +/- 2.5 min versus 10.8 +/- 7.3 min and 15.7 +/
      7.1 min). Propofol consumption was comparable in the two groups. Targeting the
      effect-site concentration improved the time course of the propofol drug effect
      during direct laryngoscopy performed during spontaneous ventilation when compared
      with manual infusion. IMPLICATIONS: This study compares the clinical profile of
      propofol anesthesia for direct laryngoscopy with spontaneous ventilation when the
      drug is administered either as a manually controlled infusion or by targeting the
      effect-site concentration through a target-controlled infusion (TCI) device. TCI
      improves the time course of propofol effects.

PMID- 11973193
TI  - An inhalation bolus of sevoflurane versus an intravenous bolus of remifentanil
      for controlling hemodynamic responses to surgical stress during major surgery: a
      prospective randomized trial.
AB  - We studied 120 patients scheduled for elective major thoracic or abdominal
      surgery, randomized into 2 groups: a Sevoflurane group (n = 63) and a
      Remifentanil group (n = 57). Heart rate (HR) and mean arterial pressure (MAP) are
      indicative of sympathetic response to surgical stress. A positive response was
      defined as a 15% increase in the HR and MAP above baseline measurements. When a
      positive response occurred, in the Sevoflurane group we administered a bolus dose
      of 8% sevoflurane (fresh gas flow 6 L/min) and in the Remifentanil group, an IV
      bolus dose of remifentanil 1 microg x kg(-1) x min(-1), which was maintained
      until MAP and HR returned to baseline measurements (effective bolus). If, after a
      bolus dose, a decrease in MAP and/or HR of >15% occurred with respect to baseline
      values, the response was considered to be excessive. The bolus dose was
      ineffective in 4.8% of the responses in the Sevoflurane group and in 17.8% of the
      responses in the Remifentanil group (P < 0.05). In the Sevoflurane group, an
      excessive effect occurred in 12% of responses, and in 26.7% in the Remifentanil
      group (P < 0.05). An inhalation bolus of sevoflurane seems to be more effective
      than an IV remifentanil bolus during maintenance, with more effective control of
      hemodynamic responses to surgical stress. IMPLICATIONS: We compared an inhalation
      bolus of sevoflurane with remifentanil for managing hemodynamic responses to
      major abdominal or thoracic surgery. This prospective, randomized trial
      demonstrated better results with sevoflurane.

PMID- 11973194
TI  - The absence of acute tolerance during remifentanil infusion in volunteers.
AB  - The development of acute opioid tolerance in humans remains controversial. We
      tested the hypothesis that continuous remifentanil infusion leads to rapid
      development of opioid tolerance. Twenty healthy male volunteers were enrolled
      onto a randomized, placebo-controlled, double-blinded, cross-over design study to
      receive a 3 h continuous infusion of remifentanil (0.08 microg x kg(-1) x min(
      1)) or saline. Test procedures included determination of pain perception
      thresholds and pain tolerance thresholds to heat and cold and neuroselective sine
      wave constant current at 5 Hz and 250 Hz. Test procedures were performed at
      baseline and then repeated at 25, 55, 85, 115, and 160 min (heat/cold) and at 35,
      65, 95, 125, and 170 min (electrical current) during infusion. No significant
      decrease of the pain threshold devolutions between 55 and 180 min after the start
      of infusion of remifentanil could be detected. In conclusion, no development of
      acute opioid tolerance was observed during constant remifentanil infusion of 3 h
      in volunteers. IMPLICATIONS: The opioid remifentanil was applied to 20 volunteers
      at a constant concentration for 3 h while pain thresholds to temperature and
      current were repeatedly assessed. Our aim was to study whether thresholds
      decrease over time because of the rapid development of opioid tolerance. No
      development of rapid opioid tolerance was observed.

PMID- 11973195
TI  - The neuropathologic effects in rats and neurometabolic effects in humans of large
      dose remifentanil.
AB  - Given in clinically relevant large doses to rats, mu-opioids produce limbic
      system hypermetabolism and histopathology. This investigation extends these
      observations, in both rats and humans, for the short-acting drug remifentanil,
      which allows more precise control and assessment of the effects of duration of
      opioid exposure. We performed two series of experiments: one in rats for
      neuropathologic effects and the second in humans for neurometabolic effects.
      Fifty mechanically ventilated rats received saline solution or remifentanil 20
      160 microg x kg(-1) x min(-1) for 3 h, followed by neuropathologic evaluation 7
      days later. Four volunteers underwent induction of anesthesia and endotracheal
      intubation with propofol and rocuronium administration followed by remifentanil
      infusion at 1-3 microg x kg(-1) x min(-1) with positron emission tomography
      evaluation of cerebral metabolic rate for glucose. In rats, dose-related
      electroencephalogram activation was evident and 19 of 40 remifentanil-treated
      rats showed brain damage, primarily in the limbic system (P < 0.01). In humans,
      cerebral metabolic rate for glucose in the temporal lobe increased from 6.29 +/-
      0.32 to 7.68 +/- 1.05 mg x 100 g(-1) x min(-1) (P < 0.05). These data indicate
      that prolonged large-dose remifentanil infusion is neurotoxic in rats with
      congruent metabolic effects with brief infusion in humans and suggest that some
      adverse effects reported in rats may be clinically relevant. IMPLICATIONS: This
      study demonstrates dose-related remifentanil neurotoxicity in physiologically
      controlled rats with congruent brain metabolic effects in four humans undergoing
      positron emission tomography evaluation during brief large-dose remifentanil
      anesthesia. These data suggest that some adverse effects reported in rats may be
      clinically relevant.

PMID- 11973196
TI  - Dystonic reaction to propofol attenuated by benztropine (cogentin).
AB  - IMPLICATIONS: Neuroexcitatory movements associated with propofol anesthesia are
      well recognized. Here we report on the successful use of benztropine (2 mg) to
      abolish abnormal dystonic movements after propofol anesthesia. Forty-five case
      reports are reviewed, and a treatment strategy for abnormal movements during
      propofol anesthesia is provided.

PMID- 11973197
TI  - Midazolam and remifentanil by bolus injection for intensely stimulating
      procedures of brief duration: experience with awake laryngoscopy.
AB  - IMPLICATIONS: The pharmacokinetic characteristics of midazolam and remifentanil
      administered by bolus injection may make them advantageous for providing brief,
      intense analgesia without prolonged respiratory depression. This application is
      particularly useful for awake, direct laryngoscopy.

PMID- 11973198
TI  - Environmental monitoring of sevoflurane and nitrous oxide using the cuffed
      oropharyngeal airway.
AB  - We compared exposure to sevoflurane (SEV) and nitrous oxide (N(2)O) during
      ventilation using the cuffed oropharyngeal airway (COPA) with waste gas exposure
      using a conventional face mask (FM) without any additional airways or face straps
      and with the laryngeal mask airway (LMA). Trace concentrations of SEV and N(2)O
      were assessed by using a direct reading spectrometer during 33 surgical
      procedures under general anesthesia. Measurements were made at the patients'
      mouths and in the anesthesiologists' breathing zones. Mean +/- SD concentrations
      of SEV and N(2)O measured at the patients' mouths were comparable in the COPA
      (SEV, 8.1 +/- 12.2 ppm; N(2)O, 213.3 +/- 289.2 ppm) and LMA (SEV, 18.5 +/- 25.8
      ppm; N(2)O, 283.4 +/- 361.0 ppm) groups but differed significantly from the FM
      group (SEV, 46.5 +/- 19.6 ppm; N(2)O, 750.7 +/- 308.3 ppm). These values resulted
      in a comparable contamination of the anesthesiologists' breathing zones (SEV, 0.5
      +/- 0.2 ppm; N(2)O, 5.7 +/- 4.8 ppm) for the COPA group, compared with the LMA
      group (SEV, 1.0 +/- 0.9 ppm; N(2)O, 12.2 +/- 14.3 ppm). This differed
      significantly from the FM group (SEV, 2.2 +/- 0.9 ppm; N(2)O, 37.5 +/- 14.3 ppm).
      We conclude that the use of the COPA during short surgical interventions has an
      occupational safety comparable to that of the LMA and that both resulted in less
      contamination through waste anesthetic gases. Therefore, the COPA may be a
      valuable alternative to the conventional FM. IMPLICATIONS: In this study, we have
      shown that the occupational exposure to waste anesthetic gases is comparable when
      using the cuffed oropharyngeal airway (COPA) and the laryngeal mask airway and is
      increased when using the face mask. Therefore, the COPA may be a valuable
      alternative to the conventional face mask during short surgical procedures.

PMID- 11973199
TI  - Pre-ictal bispectral index has a positive correlation with seizure duration
      during electroconvulsive therapy.
AB  - Propofol anesthesia increases the seizure threshold of patients receiving
      electroconvulsive therapy. Excessive neuronal suppression could result in an
      unacceptably short seizure. We sought to identify the correlation between the pre
      ictal bispectral index (BIS) score and seizure duration in patients receiving
      electroconvulsive therapy under propofol anesthesia. BIS was monitored in 38
      psychotically depressed patients. Anesthesia was induced by a bolus injection of
      1 mg/kg of propofol. The duration of muscular and electroencephalographic seizure
      was measured during the therapy. The BIS immediately before the electrical shock
      was 54 +/- 13. Both muscular and electroencephalographic seizure durations had a
      positive correlation with pre-ictal BIS (r = 0.68 and 0.73, respectively; P <
      0.01). After the electrically induced seizure, BIS decreased to 30 +/- 8,
      reflecting post-ictal suppression. BIS scores when the patients had awakened
      after the seizure had a wide variation (range, 29-81; mean, 45; SD, 13). In
      conclusion, seizure duration has a positive correlation with BIS immediately
      before electrical shock; however, BIS may not be an accurate predictor of
      awakening after electrical shock. IMPLICATIONS: Pre-ictal bispectral index had a
      positive correlation with seizure duration and could be useful to prevent an
      unacceptably short seizure in electroconvulsive therapy under propofol
      anesthesia.

PMID- 11973200
TI  - Selective and long-lasting neural blockade with resiniferatoxin prevents
      inflammatory pain hypersensitivity.
AB  - Capsaicin can produce a selective and long-lasting neural blockade.
      Resiniferatoxin (RTX) is an ultrapotent vanilloid agonist with a unique spectrum
      of activities different from that of capsaicin. We sought to determine whether a
      single application of RTX to a peripheral nerve could completely prevent the long
      lasting mechanical hyperalgesia caused by carrageenan injection. In rat
      experiments, RTX (0.001%) was administered percutaneously to the sciatic and
      saphenous nerves before the intraplantar injection of carrageenan. Responses to
      noxious mechanical (pressure on the paw) and thermal (hot plate) stimulations and
      changes in paw circumference were measured at various time intervals for 8 days
      after treatment. The administration of RTX resulted in mechanical and thermal
      hypoalgesia (for 2 and 8 days, respectively). Inflammatory hyperalgesia was
      completely prevented by the precarrageenan injection of RTX. Inflammatory
      enhancement of paw circumference was reduced by RTX (12.0 +/- 2.4 mm versus 6.9
      +/- 3.4 mm, P < 0.005). We suggest that the selective nature of the effect of
      vanilloid agonists on nociception could provide an opportunity for prolonged
      neural blockade when early mobilization and/or preservation of protective
      sensation are required. IMPLICATIONS: We report that an ultrapotent vanilloid
      agonist resiniferatoxin can provide a selective and long-lasting neural blockade.
      Applied to the sciatic and saphenous nerves, it completely prevented pain
      hypersensitivity caused by prolonged inflammatory process (injection of
      carrageenan into the paw).

PMID- 11973201
TI  - Neuroselective sensory electrodiagnostic evaluation of 4% liposomal topical
      lidocaine.
AB  - We used a neuroselective transcutaneous electrical stimulus to determine the
      onset time of cutaneous anesthesia with 4% liposomal lidocaine under occluded and
      nonoccluded conditions. The pain tolerance threshold (PTT) was used to
      atraumatically evaluate nociception. Twenty adult volunteers had liposomal
      lidocaine applied to the volar surface of each forearm for durations ranging from
      0 through 30 min (at 5-min intervals) under occluded and nonoccluded conditions.
      The PTT was determined using three different frequencies (2000 Hz, 250 Hz, 5 Hz)
      stimulating A beta, A delta, and C fibers, respectively. The time to reach the
      maximum PTT achieved defined the anesthetic onset time for each frequency. A
      differential onset of cutaneous anesthesia among the three frequencies was
      clearly demonstrated, however there was no significant difference in onset time
      between occluded and nonoccluded conditions. Blockade of C fiber transmission
      occurred significantly earlier than that of A delta (P = 0.029), which occurred
      earlier than that of A beta (P = 0.001) as determined using the Wilcoxon's signed
      rank test. We conclude that a mean onset time of approximately 4 +/- 2 min for
      blockade of C fiber transmission and 6 +/- 4 min for A delta fiber transmission
      suggests that painful stimuli such as venipuncture may be attenuated as early as
      7 min. IMPLICATIONS: An average onset time of approximately 7 min for topical 4%
      liposomal lidocaine was determined using neuroselective neurostimulation. This
      suggests that procedural pain such as venipuncture may be attenuated in this time
      frame. This technique requires correlation with conventional sensory
      measurements.

PMID- 11973202
TI  - The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent
      acute morphine tolerance.
AB  - Perioperative opioids increase postoperative pain and morphine requirement,
      suggesting acute opioid tolerance. Furthermore, opioids elicit N-methyl-D
      aspartate (NMDA)-dependent pain hypersensitivity. We investigated postfentanyl
      morphine analgesic effects and the consequences of NMDA-receptor antagonist
      (ketamine) pretreatment. The rat nociceptive threshold was measured by the paw
      pressure vocalization test. Four fentanyl boluses (every 15 min) elicited a dose
      dependent (a) increase followed by an immediate decrease of the nociceptive
      threshold and (b) reduction of the analgesic effect of a subsequent morphine
      administration (5 mg/kg): -15.8%, -46.6%, -85.1% (4 x 20, 4 x 60, 4 x 100
      microg/kg of fentanyl, respectively). Ketamine pretreatment (10 mg/kg) increased
      the fentanyl analgesic effect (4 x 60 microg/kg), suppressed the immediate
      hyperalgesic phase, and restored the full effect of a subsequent morphine
      injection. Fentanyl also elicited a delayed dose-dependent long-lasting decrease
      of the nociceptive threshold (days) that was prevented by a single ketamine
      pretreatment before fentanyl. However, a morphine administration at the end of
      the fentanyl effects restored the long-lasting hyperalgesia. Repeated ketamine
      administrations were required to obtain a complete preventive effect. Although
      ketamine had no analgesic effect per se at the dose used herein, our results
      indicate that sustained NMDA-receptor blocking could be a fruitful therapy for
      improving postoperative morphine effectiveness. IMPLICATIONS: Fentanyl-induced
      analgesia is followed by early hyperalgesia (hours), acute tolerance to the
      analgesic effects of morphine, and long-lasting hyperalgesia (days). All these
      phenomena are totally prevented by repeated administrations of the NMDA-receptor
      antagonist, ketamine, simultaneously with fentanyl and morphine administration.

PMID- 11973203
TI  - Projected complex sensations after interscalene brachial plexus block.
AB  - IMPLICATIONS: The development of projected complex sensations mimicking phantom
      pain after interscalene block is reported. The recognition of this entity is
      important because it may be confused with some other cardiac, esophageal, or
      visceral pathologies.

PMID- 11973204
TI  - Changing allocations of operating room time from a system based on historical
      utilization to one where the aim is to schedule as many surgical cases as
      possible.
AB  - Many facilities allocate operating room (OR) time based on historical utilization
      of OR time. This assumes that there is a fixed amount of regularly scheduled OR
      time, called "block time". This "Fixed Hours" system does not apply to many
      surgical suites in the US. Most facilities make OR time available for all its
      surgeons' patients, even if cases are expected to finish after the end of block
      time. In this setting, OR time should be allocated to maximize OR efficiency, not
      historical utilization. Then, cases are scheduled either on "Any Workday" (i.e.,
      date chosen by patient and surgeon) or within a reasonable time (e.g., "Four
      Weeks"). In this study, we used anesthesia billing data from two facilities to
      study statistical challenges in converting from a Fixed Hours to an Any Workday
      or Four Weeks patient scheduling system. We report relationships among the number
      of staffed ORs (i.e., first case of the day starts), length of the regularly
      scheduled OR workday, OR efficiency, OR staffing cost, and changes in services'
      OR allocations. These relationships determine the expected changes in each
      service's OR allocation, when a facility using Fixed Hours considers converting
      to the Any Workday or Four Weeks systems. IMPLICATIONS: We investigated the
      complex relationships among the number of surgical services, number of staffed
      operating rooms (ORs), length of the regularly scheduled OR workday, efficiency
      of use of OR time, OR staffing cost, and changes in each services' allocated OR
      time.

PMID- 11973205
TI  - The effect of the combined administration of colloids and lactated Ringer's
      solution on the coagulation system: an in vitro study using thrombelastograph
      coagulation analysis (ROTEG.
AB  - Gelatin solutions are often given in clinical practice once the maximal dose of a
      median-weight hydroxyethyl starch (HES) has been reached. Colloids are usually
      combined with lactated Ringer's solution (RL). Whether the combined
      administration of colloids and/or crystalloids affects blood coagulation is not
      known. We diluted blood by 20%, 40%, and 60% with RL, gelatin (Gelofusin), 6% HES
      130/0.4 (Voluven), and 6% HES 200/0.5 (Iso-Hes), as well as with combinations of
      these solutions at a ratio of 1:1 (gelatin/RL, 6% HES 130/0.4:RL, 6% HES
      200/0.5:RL, 6% HES 130/0.4:gelatin, 6% HES 200/0.5:gelatin). Thereafter, blood
      was analyzed by using modified thrombelastograph coagulation analysis (ROTEG) and
      clotting time, clot formation time, and maximal clot firmness were determined. RL
      had the least effect on hemostasis. Gelatin administered alone impaired the
      coagulation system significantly less than each median-weight HES administered
      alone. We conclude that gelatin combined with 6% HES 200/0.5 or 6% HES 130/0.4
      decreases hemostasis <6% HES 200/0.5 or 6% HES 130/0.4 administered alone.
      IMPLICATIONS: The effect of the combined administration of different colloids
      and/or crystalloids on coagulation is not known. We show that hemostasis is less
      impaired using a combination of gelatin and median-weight starches than using
      median-weight starches alone. Furthermore, the combination of lactated Ringer's
      solution and gelatin decreases the coagulation system to the same extent as the
      combination of lactated Ringer's solution and 6% hydroxyethyl starch 130/0.4.

PMID- 11973206
TI  - Continuous renal replacement therapy: anesthetic implications.

PMID- 11973207
TI  - Mild core hypothermia and anesthetic requirement for loss of responsiveness
      during propofol anesthesia for craniotomy.
AB  - Mild hypothermia may be induced during neurosurgery for brain protection.
      However, its effect on propofol requirement has not been defined. Accordingly, we
      tested the hypothesis that 3 degrees C of core hypothermia decreases the propofol
      blood concentration at which patients respond to command (CP50-awake) in
      neurosurgical patients. Forty patients were anesthetized with alfentanil 50
      microg/kg i.v., nitrous oxide, propofol target-controlled infusion, and
      rocuronium. The bispectral index (version 3.12) was monitored continuously.
      Patients were randomized to a core temperature of 34 degrees C or 37 degrees C.
      At the end of surgery, neuromuscular blockade was reversed, nitrous oxide was
      ceased, and propofol was infused to achieve a blood target determined by the
      previous patient's response. Responsiveness to command was assessed 15 min later.
      Results were analyzed with logistic regression models; P < 0.05 was considered
      statistically significant. The CP50-awake of propofol was 3.05 microg/mL (95%
      confidence interval, 2.34-3.66). Propofol concentration, but not core
      temperature, predicted loss of response to command (odds ratio, 11.76; 95%
      confidence interval, 2.40-57.63; P < 0.01). Core temperature did not alter the
      relationship between bispectral index and response to command. Propofol infusion
      regimens may not require adjustment during mild hypothermia. IMPLICATIONS:
      Neurosurgical patients may be allowed to become mildly hypothermic during
      anesthesia in an effort to provide brain protection. Propofol maintenance
      infusion doses may not require adjustment in these patients.

PMID- 11973208
TI  - Pregnancy alters adrenergic mechanisms in uterine arterioles of rats.
AB  - Pregnancy is associated with altered vascular reactivity. However, the effect of
      pregnancy on the alpha- and beta-adrenergic responses in the uterine
      microcirculation remains to be determined. In late-pregnant (Day 20-21, n = 6)
      and virgin (n = 6) Sprague-Dawley rats, uterine radial arterioles (70-120 microm
      in internal diameter) were isolated. We studied in vitro arteriolar responses in
      a pressurized, no-flow state with videomicroscopy. alpha(2)-Adrenergic activation
      relaxed uterine arterioles; this relaxation was increased with pregnancy and was
      inhibited after endothelial denudation or inhibition of nitric oxide synthase.
      Pregnancy significantly increased the contractile response to the alpha(1)
      adrenoceptor agonist phenylephrine but decreased the relaxation to the beta
      adrenoceptor agonist isoproterenol. The contractile response to the protein
      kinase C activator phorbol ester and relaxation responses to both the adenylate
      cyclase activator forskolin and the endothelium-independent cyclic guanosine
      monophosphate-mediated vaso- dilator nitroprusside were preserved. These results
      suggest that pregnancy enhances the alpha(2)-adrenoceptor-mediated relaxation of
      uterine arterioles, probably because of an increase in the release of nitric
      oxide. The alpha(1)-adrenergic response is upregulated, whereas the beta
      adrenergic response is impaired, in the uterine microcirculation of pregnant
      rats. IMPLICATIONS: Both alpha- and beta-adrenergic responses are important
      mechanisms for the regulation of uteroplacental perfusion. By use of an in
      vitromicrovascular technique, we have shown pregnancy-associated alteration in
      adrenergic responses in the uterine microcirculation of the rat.

PMID- 11973209
TI  - Continuous epidural infusion of 0.05% bupivacaine plus hydromorphone for labor
      analgesia: an observational assessment in 1830 parturients.
AB  - IMPLICATIONS: We evaluated a continuous epidural infusion containing bupivacaine
      0.05% plus the opioid hydromorphone in 1830 women requesting pain relief during
      labor and delivery. The infusion provided effective analgesia with minimal
      adverse events for patients differing in parity and at varying stages of labor.
      Pain relief was maintained in most patients without the need for epidural
      reinforcement with more concentrated doses of local anesthetic.

PMID- 11973210
TI  - The influences of maternal albumin concentrations on the placental transfer of
      propofol in human dually perfused cotyledon in vitro.
AB  - IMPLICATIONS: These results indicate that fetal exposure to propofol can vary
      considerably depending on maternal plasma albumin concentration. A fractional
      change in the maternal protein binding of propofol can result in a relatively
      large difference in fetal exposure.

PMID- 11973211
TI  - Pregnancy complicated by severe osteogenesis imperfecta: a report of two cases.
AB  - IMPLICATIONS: This case report discusses the anesthetic management of two
      parturients with severe osteogenesis imperfecta who presented for cesarean
      delivery. Although the anesthetic management for milder forms of the disease has
      been previously reported, anesthetic options for cases of this severity have not.

PMID- 11973212
TI  - Does hearing loss after spinal anesthesia differ between young and elderly
      patients?
AB  - Fifty male patients scheduled for inguinal hernia repair with spinal anesthesia
      were included in this study. The patients were divided into two groups: 25
      patients aged 30 yr or younger (Group Y) and 25 patients aged 60 yr or older
      (Group E). We performed subarachnoidal injection at the L3-4 interspace by using
      a 25-gauge Quincke needle with the patient in the sitting position, and 3 mL of
      0.5% isobaric bupivacaine was administered. Patients were evaluated by pure tone
      audiometry (LdB [low frequencies], 125-500 Hz; SdB [speech frequencies], 500-2000
      Hz; HdB [high frequencies], 2000-6000 Hz) on the day before and 2 days after
      spinal anesthesia. Low-frequency hearing loss observed in Group Y was
      significantly more common than in Group E (P < 0.01). There was no difference
      between the groups in speech and high frequencies. Mild hearing loss, defined as
      a hearing loss of 10-20 dB at two or more frequencies, was observed three times
      more frequently in Group Y than Group E (52% vs 16%; P = 0.014). We conclude that
      transient hearing loss was more common in young patients after spinal anesthesia,
      perhaps because the cerebrospinal fluid leakage after dural puncture is less in
      the elderly than in the young, a finding also associated with the infrequent
      incidence of postdural puncture headache in the elderly. IMPLICATIONS: Spinal
      anesthesia is one of the most frequently used regional anesthesia techniques in
      surgical interventions; however, rarely it may cause some transient or permanent
      neurological problems. One of these problems is headache, which is more frequent
      and severe in the young, and hearing loss, especially at low frequencies. Both
      the pain and the hearing loss are caused by leak of cerebrospinal fluid caused by
      the puncture in the membrane of the spinal cord during the procedure. We
      hypothesized that hearing loss might also be more frequent and severe in the
      young, and to test this hypothesis, we compared the hearing loss developing after
      spinal anesthesia between the young and the elderly. The implications of this
      study are as follows: First, spinal anesthesia must be performed carefully,
      especially in the young. Second, measures must be taken to avoid the leak of
      cerebrospinal fluid. This study reveals possible problems caused by spinal
      anesthesia in the young which can be easily overlooked.

PMID- 11973213
TI  - A comparison of intertendinous and classical approaches to popliteal nerve block
      using magnetic resonance imaging simulation.
AB  - The classical approach to sciatic nerve block in the popliteal fossa (popliteal
      block) often requires multiple attempts to localize the sciatic nerve. Recently,
      it has been suggested that an intertendinous approach to popliteal block may
      result in a more consistent localization of the sciatic nerve. In the current
      study, we compared anatomical landmarks for the intertendinous and classical
      approaches to popliteal block with respect to the accuracy in localizing the
      sciatic nerve using magnetic resonance imaging simulation. Two anesthesiologists
      experienced in popliteal block drew landmarks for the intertendinous and
      classical approaches on 10 volunteers; a 1.5 Tesla superconducting magnet was
      used to obtain simultaneous, 10-mm thick, fast-spin echo proton density
      transverse axial sequences of the lower extremities. Using these acquired images,
      the two approaches were simulated off-line using previously identified landmarks.
      The spatial relationships of the simulated needle paths to the nerves and vessels
      in the popliteal fossa, as well as other relevant structures, were measured and
      compared. Simulation of the intertendinous approach to popliteal block resulted
      in needle-to-sciatic nerve contact in 14 legs (70%) versus 5 legs (25%) when the
      classical approach was used (P < 0.05). We conclude that the intertendinous
      approach might result in a more consistent localization of the sciatic nerve and
      may decrease the risk of sciatic vessel puncture. IMPLICATIONS: A simulation of
      popliteal block using magnetic resonance imaging in volunteers suggests that
      using tendons of the hamstring muscles as the anatomical landmarks yields a more
      consistent localization of the sciatic nerve.

PMID- 11973214
TI  - The effects of age on neural blockade and hemodynamic changes after epidural
      anesthesia with ropivacaine.
AB  - We studied the influence of age on the neural blockade and hemodynamic changes
      after the epidural administration of ropivacaine 1.0% in patients undergoing
      orthopedic, urological, gynecological, or lower abdominal surgery. Fifty-four
      patients were enrolled in one of three age groups (Group 1: 18-40 yr; Group 2: 41
      60 yr; Group 3: > or=61 yr). After a test dose of 3 mL of prilocaine 1.0% with
      epinephrine 5 microg/mL, 15 mL of ropivacaine 1.0% was administered epidurally.
      The level of analgesia and degree of motor blockade were assessed, and
      hemodynamic variables were recorded at standardized intervals. The upper level of
      analgesia differed among all groups (medians: Group 1: T8; Group 2: T6; Group 3:
      T4). Motor blockade was more intense in the oldest compared with the youngest age
      group. The incidence of bradycardia and hypotension and the maximal decrease in
      mean arterial blood pressure during the first hour after the epidural injection
      (median of Group 1: 11 mm Hg; Group 2: 16 mm Hg; Group 3: 29 mm Hg) were more
      frequent in the oldest age group. We conclude that age influences the clinical
      profile of ropivacaine 1.0%. The hemodynamic effects in older patients may be
      caused by the high thoracic spread of analgesia, although a diminished
      hemodynamic homeostasis may contribute. IMPLICATIONS: Analgesia levels after the
      epidural administration of 15 mL of ropivacaine 1.0% increase with increasing
      age. This is associated with an increased incidence of hypotension in the
      elderly, although an effect of age on the hemodynamic homeostasis may have
      contributed. It appears that epidural doses should be adjusted for elderly
      patients.

PMID- 11973215
TI  - Isoflurane requirements during combined general/epidural anesthesia for major
      abdominal surgery.
AB  - We evaluated the effects of bupivacaine on the requirements for thiopental and
      isoflurane during combined general/epidural anesthesia. Sixty patients scheduled
      for colon resection were randomly distributed into six groups that received,
      before the induction of anesthesia, an epidural (T9-10) bolus (8 mL) followed by
      an infusion (8 mL/h) of saline (Groups 1 and 4), bupivacaine 0.0625% plus
      fentanyl 2 microg/mL (Groups 2 and 5), or bupivacaine 0.125% plus fentanyl 2
      microg/mL (Groups 3 and 6). We evaluated the amount of thiopental needed to
      abolish the eyelid reflex and the percentage of isoflurane required to maintain
      the bispectral index (BIS) between 50 and 60 (Groups 1-3) or the mean arterial
      blood pressure (MAP) within 20% of basal values (Groups 4-6). All groups required
      similar doses of thiopental (5 mg/kg); the time of evaluation, but not epidural
      treatment, had a significant effect (P < 0.0001) on BIS and MAP. After tracheal
      intubation, MAP and BIS increased by 18% and 49%, respectively (P < 0.05). In the
      bupivacaine groups, isoflurane requirements similarly decreased by 35% (P <
      0.03). For BIS and MAP, the epidural treatment (P < 0.02) and type of evaluation
      (P < 0.03) had a significant effect; MAP was lower (P < 0.05) with 0.125%
      bupivacaine. We conclude that epidural bupivacaine does not alter the thiopental
      dose, but it decreases isoflurane requirements by 35%. This study demonstrates
      that both doses of bupivacaine and fentanyl induce similar isoflurane-sparing
      effects. However, patients receiving 0.125% bupivacaine showed lower values of
      MAP when compared with controls, and thus bupivacaine 0.0625% should be favored
      during combined anesthesia. IMPLICATIONS: In patients undergoing colon resection
      under combined anesthesia, isoflurane requirements were assessed by changes in
      blood pressure or bispectral index. Epidural bupivacaine at concentrations of
      0.125% or 0.0625% (each with 2 mg/mL of fentanyl) induced the same sparing of
      isoflurane (35%). The smaller dose produced less hypotension and should be
      favored.

PMID- 11973216
TI  - Spinal anesthesia as a complication of brachial plexus block using the posterior
      approach.
AB  - IMPLICATIONS: In this case report we describe a technique used to provide local
      analgesia for surgical procedures. Although this technique has a reduced risk of
      complications, we present a patient who experienced a life-threatening paralysis
      without loss of consciousness during an attempted brachial plexus block with a
      posterior approach.

PMID- 11973217
TI  - Should we reevaluate the variables for predicting the difficult airway in
      anesthesiology?
AB  - Anesthesiologists have often been confronted with the difficult question of
      determining which patient will present an increased difficulty for endotracheal
      intubation. The limits of the previously reported morphometric airway
      measurements for predicting difficult intubation have inadequately addressed the
      normal patient population variables. We designed this prospective study to
      investigate the age and sex-related changes in the morphometric measurements of
      the airway in a large group of patients without anatomic abnormality and a group
      of cadavers. Hyomental, thyromental, sternomental distances, neck extension, and
      Mallampati scores were evaluated in 12 cadavers and in 334 patients. Patients
      were allocated to three groups based on age: Group 1 (20-30 yr), Group 2 (31-49
      yr), and Group 3 (50-70 yr). Male and female sex differences were also evaluated.
      Hyomental distance was the only variable not affected by age. In addition, the
      mean population values were less than the threshold values suggested as criteria
      for difficult endotracheal intubation. All the other criteria were age-dependent
      and inversely affected by the increase in age. Male sex was also a distinction
      for increased measurements of all the morphometric distances. The mean degree of
      neck extension was similar in both sex groups. This study provides a more
      comprehensible approach to the morphometric measurements of the human airway.
      Adequate data of normal values may help the clinician to identify patients that
      are outside the range and therefore may be challenging. IMPLICATIONS: This study
      was performed to establish data on the average values of airway morphology in the
      adult population of different age groups and sex. Hyomental, thyromental,
      sternomental distances and neck extension values were measured on 12 cadavers and
      334 patients.

PMID- 11973218
TI  - The impact of morbid obesity, pneumoperitoneum, and posture on respiratory system
      mechanics and oxygenation during laparoscopy.
AB  - We studied the effect of morbid obesity, 20 mm Hg pneumoperitoneum, and body
      posture (30 degrees head down and 30 degrees head up) on respiratory system
      mechanics, oxygenation, and ventilation during laparoscopy. We hypothesized that
      insufflation of the abdomen with CO(2) during laparoscopy would produce more
      impairment of respiratory system mechanics and gas exchange in the morbidly obese
      than in patients of normal weight. The static respiratory system compliance and
      inspiratory resistance were computed by using a Servo Screen pulmonary monitor. A
      continuous blood gas monitor was used to monitor real-time PaCO(2) and PaO(2),
      and the ETCO(2) was recorded by mass spectrometry. Static compliance was 30%
      lower and inspiratory resistance 68% higher in morbidly obese supine anesthetized
      patients compared with normal-weight patients. Whereas body posture (head down
      and head up) did not induce additional large alterations in respiratory
      mechanics, pneumoperitoneum caused a significant decrease in static respiratory
      system compliance and an increase in inspiratory resistance. These changes in the
      mechanics of breathing were not associated with changes in the alveolar-to
      arterial oxygen tension difference, which was larger in morbidly obese patients.
      Before pneumoperitoneum, morbidly obese patients had a larger ventilatory
      requirement than the normal-weight patients to maintain normocapnia (6.3 +/- 1.4
      L/min versus 5.4 +/- 1.9 L/min, respectively; P = 0.02). During pneumoperitoneum,
      morbidly obese, supine, anesthetized patients had less efficient ventilation: a
      100-mL increase of tidal volume reduced PaCO(2) on average by 5.3 mm Hg in normal
      weight patients and by 3.6 mm Hg in morbidly obese patients (P = 0.02). In
      conclusion, respiratory mechanics during laparoscopy are affected by obesity and
      pneumoperitoneum but vary little with body position. The PaO(2) was adversely
      affected only by increased body weight. IMPLICATIONS: Morbid obesity
      significantly decreases respiratory system compliance and increases inspiratory
      resistance. Increased body weight, and not altered mechanics of breathing, was
      associated with worse PaO(2) during laparoscopy.

PMID- 11973219
TI  - Anesthesia for electroconvulsive therapy.

PMID- 11973220
TI  - Thoracic epidurals and coronary artery bypass grafting surgery.

PMID- 11973221
TI  - Thoracic epidural anesthesia & analgesia in patients undergoing coronary artery
      bypass surgery.

PMID- 11973222
TI  - Malposition of the ProSeal laryngeal mask.

PMID- 11973223
TI  - Minimizing the risk of dural puncture during cervical epidural injection.

PMID- 11973224
TI  - Aprotinin and thromboembolism in liver transplantation: is there really a causal
      effect?

PMID- 11973225
TI  - Use of the Portex laryngeal mask introducer with the ProSeal LMA.

PMID- 11973226
TI  - Caveat against the use of activated recombinant factor VII for intractable
      bleeding in cardiac surgery.

PMID- 11973228
TI  - A faulty epidural catheter.

PMID- 11973227
TI  - Use of intravenous tetracosactin in the treatment of postdural puncture headache:
      our experience in forty cases.

PMID- 11973229
TI  - Mallampati class "Zero".

PMID- 11973230
TI  - The optimal location of central venous catheters.

PMID- 11973231
TI  - Arrhythmias after video assist thoracoscopy.

PMID- 11973232
TI  - The accuracy of coagulation testing.

PMID- 11973234
TI  - Eailure of the chain-link mechanism of the Ohmeda Excel 210 anesthesia machine.

PMID- 11973233
TI  - Assessing ProSeal laryngeal mask positioning: the suprasternal notch test.

PMID- 11973235
TI  - An evoked arrhythmia.

PMID- 11973236
TI  - Guidelines on perioperative cardiovascular evaluation: what have we learned over
      the past 6 years to warrant an update?

PMID- 11973238
TI  - Use of Lea symbols in young children.

PMID- 11973239
TI  - Gene therapy: new "magic bullets" to prevent ocular scarring.

PMID- 11973240
TI  - Validity of the time trade-off and standard gamble methods of utility assessment
      in retinal patients.
AB  - AIM: To assess the validity of the time trade-off (TTO) and standard reference
      gamble (SRG) techniques of utility assessment in patients with retinal disease. A
      cross section of eligible patients was studied and validity was determined
      through their relation with two logical constructs, visual acuity and scores from
      the Visual Function 14 (VF-14) index. METHODS: The study consisted of eligible
      patients presenting to a tertiary retinal facility who completed an interview.
      All patients had best corrected vision of 20/40 or worse in at least one eye. TTO
      and SRG utilities, as well as a VF-14 questionnaire, were administered through a
      standardised interview. Demographic and clinical (including Snellen visual
      acuity) information was also collected. RESULTS: 323 patients met these study
      criteria. Significant predictors of TTO utilities in the multivariate analysis
      were vision in the better seeing eye (p<0.01) and VF-14 scores (p<0.01).
      Significant predictors of standard gamble utilities were also vision in the
      better seeing eye (p<0.01) and VF-14 scores (p<0.05). CONCLUSION: Both the
      standard gamble and TTO methods demonstrate strong validity when evaluated
      against visual acuity in the better seeing eye and the VF-14 score.

PMID- 11973241
TI  - Blindness and visual impairment in the Americas and the Caribbean.
AB  - AIM: To summarise available data on the prevalence and causes of visual
      impairment and blindness in the Americas and the Caribbean. METHODS: The
      published literature was searched in Medline and LILACS using the following key
      words: blindness, visual impairment, prevalence. Articles were reviewed, and the
      references of the articles were also searched for relevant articles, which were
      also reviewed. RESULTS: Using the mortality in children under the age of 5 as an
      indicator, the overall prevalence of childhood blindness (in the under age 15
      group) for the region was estimated at 0.45/1000, with the majority (67%) living
      in countries with mortality of children under age 5 above 30/1000 live births.
      Corneal opacities were more common in countries where the under 5 year mortality
      are above 30/1000 live births and retinopathy of prematurity (ROP) was an
      important cause in countries with intermediate death rates. For adults, overall
      blindness rates were not estimated because of the social, economic, and ethnic
      diversity in the region. The primary causes of visual loss in adults in the
      Americas were age related eye diseases, notably cataract and glaucoma in the
      African-American and Hispanic populations, and age related macular degeneration
      in the white population. Uncorrected refractive error was a significant cause of
      decreased vision across ages, ethnic groups, and countries. CONCLUSION: More data
      are needed on the magnitude and causes of visual loss for the Caribbean and Latin
      American countries. Rates of blindness and visual loss from available data within
      these countries are widely disparate. Prevention and control of avoidable
      blindness needs to be an ongoing focus in this region.

PMID- 11973242
TI  - A population based eye survey of older adults in Tirunelveli district of south
      India: blindness, cataract surgery, and visual outcomes.
AB  - AIMS: To assess the prevalence of vision impairment, blindness, and cataract
      surgery and to evaluate visual acuity outcomes after cataract surgery in a south
      Indian population. METHODS: Cluster sampling was used to randomly select a cross
      sectional sample of people > or =50 years of age living in the Tirunelveli
      district of south India. Eligible subjects in 28 clusters were enumerated through
      a door to door household survey. Visual acuity measurements and ocular
      examinations were performed at a selected site within each of the clusters in
      early 2000. The principal cause of visual impairment was identified for eyes with
      presenting visual acuity <6/18. Independent replicate testing for quality
      assurance monitoring was performed in subjects with reduced vision and in a
      sample of those with normal vision for six of the study clusters. RESULTS: A
      total of 5795 people in 3986 households were enumerated and 5411 (93.37%) were
      examined. The prevalence of presenting and best corrected visual acuity > or
      =6/18 in both eyes was 59.4% and 75.7%, respectively. Presenting vision <6/60 in
      both eyes (the definition of blindness in India) was found in 11.0%, and in 4.6%
      with best correction. Presenting blindness was associated with older age, female
      sex, and illiteracy. Cataract was the principal cause of blindness in at least
      one eye in 70.6% of blind people. The prevalence of cataract surgery was 11.8%
      with an estimated 56.5% of the cataract blind already operated on. Surgical
      coverage was inversely associated with illiteracy and with female sex in rural
      areas. Within the cataract operated sample, 31.7% had presenting visual acuity >
      or =6/18 in both eyes and 11.8% were <6/60; 40% were bilaterally operated on,
      with 63% pseudophakic. Presenting vision was <6/60 in 40.7% of aphakic eyes and
      in 5.1% of pseudophakic eyes; with best correction the percentages were 17.6% and
      3.7%, respectively. Refractive error, including uncorrected aphakia, was the main
      cause of visual impairment in cataract operated eyes. Vision <6/18 was associated
      with cataract surgery in government, as opposed to that in non
      governmental/private facilities. Age, sex, literacy, and area of residence were
      not predictors of visual outcomes. CONCLUSION: Treatable blindness, particularly
      that associated with cataract and refractive error, remains a significant problem
      among older adults in south Indian populations, especially in females, the
      illiterate, and those living in rural areas. Further study is needed to better
      understand why a significant proportion of the cataract blind are not taking
      advantage of free of charge eye care services offered by the Aravind Eye Hospital
      and others in the district. While continuing to increase cataract surgical volume
      to reduce blindness, emphasis must also be placed on improving postoperative
      visual acuity outcomes.

PMID- 11973243
TI  - Examination of young children with Lea symbols.
AB  - AIMS: In order to establish normal values and interocular differences of visual
      acuity, Lea symbols were applied to neurologically and ophthalmologically normal
      children. METHODS: 385 children (21-93 months old) were examined, within a
      routine check up in an urban paediatric practice where Lea symbol acuity (LS) was
      measured. Of these children, 90 were re-examined in hospital comparing Lea symbol
      acuity (LS) and Landolt C acuity (LC). Strabismus, ametropia, and any organic eye
      disease were excluded. RESULTS: In the paediatric practice, LS could be measured
      on both eyes in 54% of the children. In the age group above 36 and 48 months the
      success rate was 76% and 95%, respectively. Acuity in the paediatric practice
      ranged from 0.1 to 2.0 (median 1.25) in the whole group. Interocular acuity
      difference was one line or less in 80%. In the hospital, LS and LC could be
      measured on both eyes of 77% and 48% of the 90 children, respectively.
      Cooperation increased with age. LS in the hospital ranged from 0.32 to 2.0
      (median 1.0) and LC from 0.16 to 1.25 (median 0.8). Interocular difference of LS
      acuity was one line or less in 90%. CONCLUSION: Lea symbols were found to be
      useful for visual acuity assessment in early childhood. Significant variability
      of visual acuity in this age group is caused by cooperation. When monocular
      measurements are possible on both eyes, however, the intraindividual interocular
      difference of visual acuity usually does not exceed one line.

PMID- 11973244
TI  - S antigen specific effector T cell activation detected by cytokine flow
      cytometry.
AB  - BACKGROUND/AIMS: Effector T cell activation is particularly important in the
      initiation of autoimmune uveitis. This pilot study seeks to demonstrate
      activation of human peripheral effector T cells in response to the uveitis
      candidate autoantigen, retinal S antigen (SAg), using cytokine flow cytometry
      (CFC). METHODS: Peripheral blood mononuclear cell (PBMC) suspensions from uveitis
      patients and controls were stimulated with bovine SAg. Activation responses were
      detected by CFC. RESULTS: Electronic gating enabled analysis of CD69+, IFN-gamma+
      CD4+ lymphocytes. An SAg specific response was detectable in four of 13 patients
      and four of eight controls. CONCLUSION: SAg specific, peripheral, effector T cell
      activation can be detected by CFC. Similar levels of responsiveness were seen in
      patient and control groups. More detailed cytokine profiling may demonstrate
      functional differences between the groups.

PMID- 11973245
TI  - High dose intravenous steroid therapy for severe posterior segment uveitis in
      Behcet's disease.
AB  - AIM: To evaluate the safety and effectiveness of high dose intravenous steroid
      therapy (HDIST) in Behcet's disease patients with severe posterior segment
      uveitis attacks. METHODS: Five patients with ocular Behcet's disease were treated
      with HDIST for severe posterior segment attacks. Two patients had vasculitis, one
      patient had papillitis, and the other two had retinitis; four patients also had
      accompanying severe vitritis. The visual acuities and improvement in ocular signs
      after HDIST were evaluated. RESULTS: During HDIST, patients had no systemic
      complications caused by treatment. All patients responded to HDIST with evidence
      of a decrease in intraocular inflammatory activity and improved visual acuities
      within a mean time of 7 (1-15) days of commencing treatment. During follow up
      three out of five patients had new posterior segment attacks. CONCLUSION: HDIST
      is effective in controlling severe, vision threatening acute posterior segment
      Behcet's uveitis attacks and in improving visual function in a short period of
      time

PMID- 11973246
TI  - An evaluation of the administration of sub-Tenon local anaesthesia by a nurse
      practitioner.
AB  - AIM: To evaluate the administration of sub-Tenon local anaesthesia (LA) by a
      nurse practitioner. METHODS: 106 consecutive patients listed for cataract surgery
      were given sub-Tenon's anaesthesia by a nurse practitioner. The surgical
      procedure was performed within 15 minutes of the administration of the LA. Pain,
      state and adequacy of anaesthesia, appearance of the eye, and patient anxiety
      were measured. Patients' experiences of this new nursing role were gained through
      interview. RESULTS: At the beginning of surgery, few patients showed eye movement
      in any of the four quadrants and the surgeons reported that akinesia was
      inadequate in only seven (7.1%) cases. Three patients (3.3%) gave a pain score of
      3 out of 10 or above during surgery whereas the surgeons assessed the pain relief
      to be inadequate in eight (8.1%) cases. Five (5.3%) patients required a top up of
      anaesthesia and 51 (39.8%) patients developed conjunctival chemosis in two or
      more quadrants. Overall, patients' comments indicate that they were pleased with
      the new service. CONCLUSION: The results suggest that nurse practitioner
      delivered sub-Tenon LA is an effective and safe method of LA administration for
      cataract surgery.

PMID- 11973247
TI  - Intravitreal triamcinolone in subfoveal recurrence of choroidal
      neovascularisation after laser treatment in macular degeneration.
AB  - BACKGROUND: Laser treatment of extrafoveal well delineated choroidal
      neovascularisation in exudative age related macular degeneration has a high rate
      of failure with subsequent severe vision loss from subfoveal involvement. Laser
      treatment may limit scotoma size, but is unpalatable because of early persistent
      vision loss. Intravitreal triamacinolone injection may be an acceptable
      alternative therapy in such disparate cases. METHODS: 14 consecutive patients
      with recurrent neovascularisation were treated with a single 4.0 mg injection of
      triamacinolone and followed for up to 1 year. Visual results were compared with
      published data from the Macular Photocoagulation Study of recurrent
      neovascularisation. RESULTS: Mean visual acuity remained stable at about 20/200
      throughout the study period in the treated patients. This is comparable to the
      outcomes in the Macular Photocoagulation Study for laser retreated patients, and
      better than the observation group. CONCLUSIONS: Intravitreal triamcinolone may be
      an acceptable treatment of subfoveal recurrent neovascularisation while avoiding
      early persistent vision loss from laser retreatment.

PMID- 11973248
TI  - Effect of prior steroid treatment on temporal artery biopsy findings in giant
      cell arteritis.
AB  - AIM: To examine the effect of up to 6 weeks of corticosteroid treatment on the
      positive temporal artery biopsy rate in giant cell arteritis (GCA). METHODS:
      Prospective comparative clinical study of 11 patients meeting the American
      College of Rheumatology criteria for diagnosis of GCA. Patients underwent
      temporal artery biopsy within 1 week, at 2-3 weeks, or after 4 weeks of
      corticosteroid treatment. RESULTS: Overall, nine of 11 (82%) patients had
      positive temporal artery biopsies. Six of seven (86%) biopsies performed after 4
      or more weeks of steroid treatment were positive. CONCLUSION: Temporal artery
      biopsy is useful several weeks after institution of steroids.

PMID- 11973249
TI  - External dacryocystorhinostomy for the treatment of acquired partial nasolacrimal
      obstruction in adults.
AB  - AIM: To determine the long term success of external dacryocystorhinostomy (DCR)
      in adults with acquired partial nasolacrimal obstruction. METHODS: A
      retrospective study of 50 external dacryocystorhinostomies with silicone
      intubation performed for partial nasolacrimal obstruction, was undertaken.
      Preoperative lacrimal scintigraphy divided drainage abnormalities into presac or
      postsac delays. Postoperative success was determined by lacrimal patency to
      irrigation, a positive dye test on nasal endoscopy and subjective resolution of
      epiphora. Statistical analysis was performed using the Fisher exact test.
      RESULTS: A patent DCR system to irrigation and a positive dye test was achieved
      in 90% of procedures. At an average of 3.6 months' follow up, subjective success
      was reported in 84% of cases-91% for postsac and 67% for presac delays. At 3
      years' follow up success had declined to 70% overall and to 80% and 47% for
      postsac and presac occlusions respectively. There was a statistically significant
      association between a presac delay and postoperative recurrence of epiphora, p =
      0.04. CONCLUSION: External DCR with silicone intubation is an effective procedure
      for partial nasolacrimal obstruction. Presac delays do significantly less well
      and further studies are necessary to evaluate the best type of surgery for these
      patients.

PMID- 11973250
TI  - Acanthamoeba keratitis in England and Wales: incidence, outcome, and risk
      factors.
AB  - AIM: To determine the incidence, regional variation in frequency, outcome, and
      risk factors for acanthamoeba keratitis (AK) in England and Wales. METHODS: AK
      cases presenting from 1 October 1997 to 30 September 1999 were identified by the
      British Ophthalmic Surveillance Unit active reporting system. Clinical and
      patient postal questionnaire data were analysed. RESULTS: 106 reported cases met
      study criteria. The annual incidence for the 2 years was 1.26 and 1.13 per
      million adults and, for contact lens (CL) wearers, 21.14 and 17.53 per million.
      There was marked regional variation in incidence (0 to 85.13 per million adult CL
      wearers), with CL wearers in the south having a ninefold increased risk of AK
      compared with those resident in the north (95% confidence limits: 2.2-38.9,
      p<0.0001), and a threefold increased risk with hard as opposed to soft domestic
      water (95% confidence limits: 1.73 to 6.58, p<0.001). Treatment and outcome data
      were similar to those previously reported. 93/106 (88%) patients were CL wearers.
      Among these, 46/77 (60%) were disinfecting irregularly, and 20/63 (32%) had been
      swimming in CLs. One step hydrogen peroxide and chlorine release soft CL (SCL)
      disinfection systems were significantly over-represented among the cases. Among
      SCL users, one or more previously established risk factors for AK were identified
      in 50/55 (91%) patients. CONCLUSIONS: The incidence was considerably higher than
      most previous estimates, and was static. The geographical variation in incidence
      may be partly related to the increase in risk associated with hard water. The
      fact that water quality can have such an effect on the risk of AK suggests that
      many CL wearers must be letting tapwater come into contact with their lenses or
      storage cases. Improved education for CL wearers and practitioners about hygiene
      practice and the variable efficacy of contact lens systems could be expected to
      reduce the incidence of this disease.

PMID- 11973251
TI  - Does prospective monitoring improve cataract surgery outcomes in Africa?
AB  - AIMS: To determine if prospective monitoring influences cataract surgical
      outcomes in east Africa. METHODS: A prospective observational study of all
      routine extracapsular cataract extractions with posterior chamber lens implants
      carried out at Kikuyu Eye Unit, Kenya, between 1 January 1999 and 31 December
      1999. RESULTS: Out of 1845 eligible eyes 1800 were included in the study. Two
      months' follow up was available in 67.2% of patients. The proportion achieving a
      good outcome increased steadily from 77.1% in the first quarter to 89.4% in the
      fourth quarter (chi(2) for trend, p<0.001). There was no change in the incidence
      of operative complications; however, the proportion of patients achieving a good
      visual outcome following vitreous loss increased from 47.2% in the first 6 months
      to 71.0% in the last 6 months (chi(2) p<0.05). Of the eyes with poor outcome
      (best corrected acuity <6/60 at 2 months) half were due to pre-existing eye
      diseases. The proportion of patients with known ocular comorbidity decreased from
      10.2% in the first quarter to 5.9% in the fourth quarter (chi(2) for trend,
      p<0.05). Poor outcome was associated with age over 80 years, known diabetes,
      preoperative bilateral blindness, any ocular comorbidity, and intraoperative
      vitreous loss. CONCLUSIONS: This study demonstrates improvement in visual outcome
      results after cataract surgery over a 1 year period. Monitoring of outcomes
      appears to be associated with a change in surgeons' attitudes, leading to greater
      emphasis on appropriate case selection, better management of surgical
      complications, and improved visual outcomes.

PMID- 11973252
TI  - Childbearing and risk of cataract in young women: an epidemiological study in
      central India.
AB  - BACKGROUND/AIMS: Observations in central India, over a period of more than a
      decade, suggested that the frequency of sight restoring cataract surgery was
      substantially higher in women of childbearing age compared to men of the same
      age. Formal surveys in the subcontinent of India have confirmed a higher
      prevalence of cataract in women. The present study was conducted to explore
      possible effects of childbearing and associated adverse factors on cataract risk.
      METHODS: A case-control study design was used. Cases were mothers aged 35-45 with
      bilateral "senile" cataract. Controls were mothers of the same age but with clear
      lenses, attending the hospital services with other, mostly minor, complaints.
      RESULTS: A significant association was found between childbearing and risk of
      sight impairing cataract in mothers. Having more than three babies doubled the
      risk (adjusted odds ratio 2.0, p=0.012), and the risk increased by an estimated
      20% for each additional birth. The birth effect was independent of age,
      socioeconomic status (occupation and income level), body mass index, and multiple
      episodes of severe dehydration, all regarded as putative risk factors for
      cataract. CONCLUSIONS: Having more than three babies may substantially increase
      the risk of sight impairing cataract in mothers of childbearing age in central
      India. The findings open new research challenges to identify cataract risk
      factors to which mothers may be exposed during pregnancy and childbirth,
      particularly under poor socioeconomic conditions.

PMID- 11973254
TI  - Optic disc cup slope and visual field indices in normal, ocular hypertensive and
      early glaucomatous eyes.
AB  - AIM: To evaluate the correlation between internal slope analysis of the optic
      nerve head and visual field changes in normal eyes and those with ocular
      hypertension (OHT) and early glaucoma (POAG). METHODS: One eye of each of 22
      normal subjects, 21 patients with ocular hypertension, and 50 patients with
      glaucoma were examined using the TopSS scanning laser ophthalmoscope. A series of
      topographic parameters measuring the internal features of the optic discs of
      these patients were obtained. These findings were compared with the Humphrey
      visual field analysis of these patients. RESULTS: Global topographic average
      slope and cup to disc ratio could discriminate between groups of normal and OHT
      patients (p = 0.02). All global and sector analysis parameters could discriminate
      normal subjects from POAG patients. The average slope parameter provided the best
      separation with a receiver operating characteristic curve area of 0.88. Visual
      field mean deviation (MD) was most closely correlated with global average slope
      (r = -0.60, p<10(-7)) and cup to disc ratio (r = -0.40, p<0.001). Visual field MD
      was also well correlated (r = -0.50, p<0.0001) with slope parameters for sectors
      S8, S2, and S1. CONCLUSION: Average slope, a parameter independent of reference
      planes and magnification effects, is capable of discriminating groups of OHT and
      POAG patients from a group of normal subjects. This topographic parameter is also
      well correlated with the visual field MD. Sector slope analysis suggests early
      glaucomatous damage may occur in the inferotemporal region of the optic disc.

PMID- 11973253
TI  - The effects of new topical treatments on management of glaucoma in Scotland: an
      examination of ophthalmological health care.
AB  - BACKGROUND: The management of glaucoma has been changed in the past decade by the
      introduction of new drugs. The impact of these changes on clinical care of
      patients was examined by examining operation and prescribing rates for glaucoma
      in four geographical areas of Scotland for the years 1994 to 1999. METHODS: A
      retrospective analysis of national health statistics: primary care prescribing
      data, hospital derived operation rates, consultant numbers, optometrist numbers,
      and eye test data, expressed by estimated population at risk of glaucoma. The
      outcome measures were prescribing volume and cost for glaucoma medications, and
      operation rates, corrected for population estimated to be at risk of glaucoma
      (PEG), for trabeculectomy, for Scotland as a whole, and for four geographical
      "regions" (north east, south east, central, and south west Scotland). RESULTS:
      Prescribed items per 1000 population estimated to have glaucoma (PEG) increased
      by 24.9% between 1994 and 1999. This was above the general increase in
      prescribing in Scotland (17.8%). This increase varied in the four health regions
      evaluated (14.3% to 31.9%). Prescribing of topical beta blockers increased little
      (6.4%), but there was a large increase in the use of new products (topical
      prostaglandins, carbonic anhydrase inhibitors, and alpha(2) agonists), at the
      expense of miotics (47.7% fall), and older sympathomimetics. This change in
      prescribing pattern was accompanied by a 61.5% increase in cost (range 42.2% to
      73.4% in the four regions). New drugs accounted for more than half of total
      glaucoma expenditure in 1999. Operation rates (corrected for PEG) fell by 45.9%
      (range 43.1 to 58.6%) between 1994 and 1999. Other indicators suggested increased
      activity in ophthalmic areas (for example, cataract operations, eye tests,
      numbers of optometrists and ophthalmic surgeons all increased). Within north east
      Scotland operation rates decreased and prescribing increased less than in other
      regions, both from lowest regional baseline in 1994. CONCLUSIONS: The
      introduction of new drug classes has had dramatic effects on the prescribing of
      glaucoma treatments. There has been a decline in older treatments and an increase
      in new agents, which has been associated with a large reduction in operation
      rates for glaucoma in Scotland over 6 years. Comparison of prescribing and
      operation data indicates regional differences in healthcare delivery for
      glaucoma.

PMID- 11973255
TI  - Frequency of testing for detecting visual field progression.
AB  - AIMS: To investigate the effect of frequency of testing on the determination of
      visual field progression using pointwise linear regression (PLR). METHODS: A
      "virtual eye" was developed to simulate series of sensitivities over time at a
      given point in the eye. The user can input the actual behaviour of the point (for
      example, stable or deteriorating steadily), and then a configurable amount of
      noise is added to produce a realistic series over time. The advantage of this
      over using patient data is that the actual status of the eye is known. Series
      were generated using different frequencies of testing, and the diagnosis that
      would have been made from each series was compared with the true status of the
      eye. A point was diagnosed as progressing if the regression line for the series
      showed a deterioration of at least 1 dB per year, significant at the 1% level.
      From these results, graphs were produced showing the number of points correctly
      or incorrectly diagnosed as progressing. RESULTS: With the virtual eye
      deteriorating at a rate of 2 dB/year, it was found that the point was determined
      to be progressing quicker when more tests were carried out each year. With a
      stable virtual eye, it was found that increasing the frequency of testing
      increased the number of series that were falsely labelled as progressing during
      the first 3 years of testing. CONCLUSIONS: As the frequency of testing increases,
      the sensitivity of PLR increases. However, the specificity decreases; possibly
      meaning more unnecessary changes in treatment. Three tests per year provide a
      good compromise between sensitivity and specificity.

PMID- 11973256
TI  - A prospective, case controlled study of the natural history of diabetic
      retinopathy and maculopathy after uncomplicated phacoemulsification cataract
      surgery in patients with type 2 diabetes.
AB  - AIM: To determine if uncomplicated phacoemulsification cataract surgery is
      associated with an accelerated rate of progression of diabetic retinopathy or
      maculopathy postoperatively. METHODS: A prospective trial of 50 type 2 diabetics
      undergoing monocular phacoemulsification cataract surgery by a single consultant
      surgeon. The grade of diabetic retinopathy and diabetic maculopathy in the
      operated and non-operated fellow eye was assessed preoperatively and for 12
      months postoperatively. RESULTS: Overall, retinopathy progression was observed in
      11 patients. In seven the retinopathy progressed in both eyes, in three it
      progressed in the operated eye alone, and in one it progressed in the fellow eye
      alone. Macular oedema was observed in 13 eyes postoperatively. Four had transient
      pseudophakic cystoid macular oedema and nine true diabetic maculopathy. Where
      maculopathy progressed it did so symmetrically in five patients, it progressed in
      the operated eye alone in four patients, and the fellow eye alone in two
      patients. There was no significant difference in the number of operated and
      fellow eyes whose retinopathy or maculopathy progressed postoperatively. In both
      the operated (OE) and non-operated (NoE) eyes retinopathy progression was
      associated with a higher mean HbA(1)C (OE p=0.003; NoE p=0.001) and insulin
      treatment (OE p=0.008, NoE p=0.04). CONCLUSION: Uncomplicated phacoemulsification
      cataract surgery does not cause acceleration of diabetic retinopathy
      postoperatively and any progression that is observed probably represents the
      natural history of the disease. Although macular oedema is common after cataract
      surgery it may follow a benign course and in many patients the development of
      clinically significant macular oedema postoperatively probably represents natural
      disease progression rather than being a direct effect of surgery.

PMID- 11973257
TI  - Clinical characteristics of retinal venous occlusions occurring at different
      sites.
AB  - AIMS: To identify the contributory factors associated with different sites of
      occlusion and the presence or absence of optic nerve head swelling (ONHS).
      METHODS: 874 cases of retinal venous occlusion (RVO) were prospectively examined
      at a tertiary referral centre and classified according to three defined sites of
      occlusion: arteriovenous crossing RVO (AV-RVO); optic cup RVO (OC-RVO); and optic
      nerve sited RVO. Optic nerve sited RVOs were further divided on the basis of
      presence (ONHS-RVO) and absence (NONHS-RVO) of ONHS. RVOs not occurring at any of
      the defined sites were grouped as no-site RVO (NS-RVO). Important clinical
      parameters were compared among four of the five subgroups by multivariate
      analysis of variance and chi(2) test (NS-RVO excluded). RESULTS: The overall
      multivariate analysis of variance for differences in the mean age, systolic and
      diastolic blood pressure, body mass index, and intraocular pressure (IOP) among
      the four subgroups were highly significant (p <0.0001). The F ratios indicated
      that the differences in the mean age and IOP accounted for this statistical
      trend. The mean age was statistically significantly lower in the ONHS-RVO group
      compared to the rest of the groups (p <0.0001). The mean age was significantly
      higher in OC-RVO compared to the AV-RVO group (p <0.05). The mean IOP was
      significantly higher in OC-RVO than in the rest of the groups (p <0.01 to
      0.0001), while it was also higher in the NONHS-RVO group compared to the ONHS-RVO
      and AV-RVO groups (p <0.0001). The prevalence of primary open angle glaucoma
      (POAG), sex, laterality, involvement of the fellow eye, smoking and hypertension
      were compared by chi(2) tests. POAG was significantly more prevalent in the OC
      RVO group than in the rest of the groups (p <0.0083), while it was also
      significantly more prevalent in the NONHS-RVO group compared to AV-RVO or ONHS
      RVO (p <0.0083) groups. Smoking was significantly more prevalent in AV-RVO than
      in the rest of the groups (p <0.05). The proportion of male sex was significantly
      higher in ONHS-RVO compared to the AV-RVO group (p <0.05). Hypertension was
      significantly more prevalent in the AV-RVO than in the ONHS-RVO or NONHS-RVO
      groups (p <0.05). CONCLUSION: A new classification of RVO based on the site of
      occlusion and ONHS has been evaluated. The higher prevalence of hypertension and
      smoking in AV-RVO suggests a particular importance of cardiovascular risk factors
      in this group. The association of POAG with CRVO has been confirmed, but only for
      those cases without ONHS. A distinctive relation between raised IOP and OC-RVO
      has been demonstrated, suggesting a causal association. RVOs with ONHS tend to
      occur in younger people, with a higher proportion of males, and a lower
      prevalence of hypertension and POAG, suggesting that other causal factors may be
      important in this group. The new scheme resolves the confusion in the literature
      regarding classification of RVO, and has diagnostic, causal, prognostic, and
      therapeutic implications.

PMID- 11973258
TI  - A new delivery system for 5-fluorouracil using prodrug and converting enzyme.
AB  - AIMS: To evaluate a new delivery system of 5-fluorouracil (5-FU) using 5
      fluorocytosine (5-FC) as a prodrug and cytosine deaminase induced in vitro and in
      vivo. METHODS: Fibroblastic cells from rabbit Tenon's capsule were cultured. The
      cells were exposed to 5-FU and 5-FC with or without cytosine deaminase induced by
      recombinant adenovirus. In the in vitro study, cell proliferation and DNA
      synthesis were assessed by MTS, BrdU assay. The effect of 5-FC removal after the
      treatment of 5-FC and cytosine deaminase induction was also assayed. In the in
      vivo study cells with or without cytosine deaminase induction were transplanted
      into the subconjunctival space of mice, followed by eye drops of 1000 microg/ml
      of 5-FC three times a day. The mice were sacrificed at days 1, 5, and 10, then
      the cells transplanted were evaluated. RESULTS: Cell proliferation was inhibited
      by exposure to 5-FU in a dose dependent manner; however, up to 1000 microg/ml of
      5-FC did not affect cell proliferation. Cell proliferation was inhibited by
      exposure to 5-FC in a time dependent manner with induction of cytosine deaminase
      following infection of recombinant adenovirus. When 5-FC was removed 3 or 6 days
      after the treatment, the cells grew again. The effect was reproduced in the in
      vivo model of subconjunctival cellular proliferation although 5-FC was
      administrated as eye drops. There were no cases with corneal erosion. CONCLUSION:
      Cell proliferation was inhibited by co-exposure of 5-FC and cytosine deaminase.
      This new delivery system may merit controlled delivery of 5-FU after filtering
      surgery.

PMID- 11973260
TI  - Needle aspiration of a traumatic subperiosteal haematoma of the orbit.

PMID- 11973259
TI  - The sclera, the prion, and the ophthalmologist.
AB  - Prions have emerged in the past 5 years as serious transmissible infective
      agents. Ocular tissue transplantation has come under scrutiny after potential
      infected tissue was transplanted into healthy patients. In this review we examine
      the evidence for the risk of transmission of prions after scleral transplantation
      and explore alternative materials that may be used in ocular surgery.

PMID- 11973262
TI  - Stellate tarsoconjunctival lesions in ocular adenoviral infection.

PMID- 11973261
TI  - Drug induced acute myopia with supraciliary choroidal effusion in a patient with
      Wegener's granulomatosis.

PMID- 11973263
TI  - Cutaneous presentation of orbital follicular lymphoma: clinical differential
      diagnosis with lymphocytoma cutis.

PMID- 11973265
TI  - A role for iro1 and iro7 in the establishment of an anteroposterior compartment
      of the ectoderm adjacent to the midbrain-hindbrain boundary.
AB  - We have identified a novel Iroquois (Iro) gene, iro7, in zebrafish. iro7 is
      expressed during gastrulation along with iro1 in a compartment of the dorsal
      ectoderm that includes the prospective midbrain-hindbrain domain, the adjacent
      neural crest and the trigeminal placodes in the epidermis. The iro1 and iro7
      expression domain is expanded in headless and masterblind mutants, which are
      characterized by exaggerated Wnt signaling. Early expansion of iro1 and iro7
      expression in these mutants correlates with expansion of the midbrain-hindbrain
      boundary (MHB) domain, the neural crest and trigeminal neurons, raising the
      possibility that iro1 and iro7 have a role in determination of these ectodermal
      derivatives. A knockdown of iro7 function revealed that iro7 is essential for the
      determination of neurons in the trigeminal placode. In addition, a knockdown of
      both iro1 and iro7 genes uncovered their essential roles in neural crest
      development and establishment of the isthmic organizer at the MHB. These results
      suggest a new role for Iro genes in establishment of an ectodermal compartment
      after Wnt signaling in vertebrate development. Furthermore, analysis of activator
      or repressor forms of iro7 suggests that iro1 and iro7 are likely to function as
      repressors in establishment of the isthmic organizer and neural crest, and Iro
      genes may have dual functions as repressors and activators in neurogenesis.

PMID- 11973266
TI  - Germ cell expression of the transcriptional co-repressor TIF1beta is required for
      the maintenance of spermatogenesis in the mouse.
AB  - The gene for transcriptional intermediary factor 1beta (TIF1beta) encodes a
      transcriptional co-repressor known to play essential roles in chromatin
      remodeling as well as in early embryonic development. During spermatogenesis,
      TIF1beta is preferentially associated with heterochromatin structures of Sertoli
      cells and round spermatids, as well as with meiotic chromosomes. Its expression
      is tightly regulated within spermatocyte and spermatid populations, and it is
      undetectable in spermatogonia. Spatiotemporally controlled ablation of TIF1beta
      by using a germ cell lineage-specific CreER(T)/loxP system leads to testicular
      degeneration. This degeneration is not due to impairment of chromatin remodeling
      processes during meiosis and spermiogenesis, as TIF1beta-deficient spermatocytes
      are able to complete their differentiation into spermatozoa. It rather occurs as
      a consequence of shedding of immature germ cells (spermatocytes and spermatids),
      and disappearance of stem spermatogonia. These results indicate that TIF1beta has
      important functions in the homeostasis of the seminiferous epithelium, and
      probably plays a crucial role in the network of paracrine interactions between
      germ cell subpopulations and/or Sertoli cells.

PMID- 11973267
TI  - Knockdown of duplicated zebrafish hoxb1 genes reveals distinct roles in hindbrain
      patterning and a novel mechanism of duplicate gene retention.
AB  - We have used a morpholino-based knockdown approach to investigate the functions
      of a pair of zebrafish Hox gene duplicates, hoxb1a and hoxb1b, which are
      expressed during development of the hindbrain. We find that the zebrafish hoxb1
      duplicates have equivalent functions to mouse Hoxb1 and its paralogue Hoxa1.
      Thus, we have revealed a 'function shuffling' among genes of paralogue group 1
      during the evolution of vertebrates. Like mouse Hoxb1, zebrafish hoxb1a is
      required for migration of the VIIth cranial nerve branchiomotor neurons from
      their point of origin in hindbrain rhombomere 4 towards the posterior. By
      contrast, zebrafish hoxb1b, like mouse Hoxa1, is required for proper segmental
      organization of rhombomere 4 and the posterior hindbrain. Double knockdown
      experiments demonstrate that the zebrafish hoxb1 duplicates have partially
      redundant functions. However, using an RNA rescue approach, we reveal that these
      duplicated genes do not have interchangeable biochemical functions: only hoxb1a
      can properly pattern the VIIth cranial nerve. Despite this difference in protein
      function, we provide evidence that the hoxb1 duplicate genes were initially
      maintained in the genome because of complementary degenerative mutations in
      defined cis-regulatory elements.

PMID- 11973268
TI  - Low proliferative and high migratory activity in the area of Brachyury expressing
      mesoderm progenitor cells in the gastrulating rabbit embryo.
AB  - General mechanisms initiating the gastrulation process in early animal
      development are still elusive, not least because embryonic morphology differs
      widely among species. The rabbit embryo is revived here as a model to study
      vertebrate gastrulation, because its relatively simple morphology at the
      appropriate stages makes interspecific differences and similarities particularly
      obvious between mammals and birds. Three approaches that centre on mesoderm
      specification as a key event at the start of gastrulation were chosen. (1) A cDNA
      fragment encoding 212 amino acids of the rabbit Brachyury gene was cloned by RT
      PCR and used as a molecular marker for mesoderm progenitors. Whole-mount in situ
      hybridisation revealed single Brachyury-expressing cells in the epiblast at 6.2
      days post conception, i.e. several hours before the first ingressing mesoderm
      cells can be detected histologically. With the anterior marginal crescent as a
      landmark, these mesoderm progenitors are shown to lie in a posterior quadrant of
      the embryonic disc, which we call the posterior gastrula extension (PGE), for
      reasons established during the following functional analysis. (2) Vital dye (DiI)
      labelling in vitro suggests that epiblast cells arrive in the PGE from anterior
      parts of the embryonic disc and then move within this area in a complex pattern
      of posterior, centripetal and anterior directions to form the primitive streak.
      (3) BrdU labelling shows that proliferation is reduced in the PGE, while the
      remaining anterior part of the embryonic disc contains several areas of increased
      proliferation. These results reveal similarities with the chick with respect to
      Brachyury expression and cellular migration. They differ, however, in that local
      differences in proliferation are not seen in the pre-streak avian embryo. Rather,
      rabbit epiblast cells start mesoderm differentiation in a way similar to
      Drosophila, where a transient downregulation of proliferation initiates mesoderm
      differentiation and, hence, gastrulation.

PMID- 11973269
TI  - Depletion of definitive gut endoderm in Sox17-null mutant mice.
AB  - In the mouse, the definitive endoderm is derived from the epiblast during
      gastrulation, and, at the early organogenesis stage, forms the primitive gut
      tube, which gives rise to the digestive tract, liver, pancreas and associated
      visceral organs. The transcription factors, Sox17 (a Sry-related HMG box factor)
      and its upstream factors, Mixer (homeobox factor) and Casanova (a novel Sox
      factor), have been shown to function as endoderm determinants in Xenopus and
      zebrafish, respectively. However, whether the mammalian orthologues of these
      genes are also involved with endoderm formation is not known. We show that Sox17(
      /-) mutant embryos are deficient of gut endoderm. The earliest recognisable
      defect is the reduced occupancy by the definitive endoderm in the posterior and
      lateral region of the prospective mid- and hindgut of the headfold-stage embryo.
      The prospective foregut develops properly until the late neural plate stage.
      Thereafter, elevated levels of apoptosis lead to a reduction in the population of
      the definitive endoderm in the foregut. In addition, the mid- and hindgut tissues
      fail to expand. These are accompanied by the replacement of the definitive
      endoderm in the lateral region of the entire length of the embryonic gut by cells
      that resemble the visceral endoderm. In the chimeras, although Sox17-null ES
      cells can contribute unrestrictedly to ectodermal and mesodermal tissues, few of
      them could colonise the foregut endoderm and they are completely excluded from
      the mid- and hindgut endoderm. Our findings indicate an important role of Sox17
      in endoderm development in the mouse, highlighting the idea that the molecular
      mechanism for endoderm formation is likely to be conserved among vertebrates.

PMID- 11973270
TI  - A novel disintegrin domain protein affects early cell type specification and
      pattern formation in Dictyostelium.
AB  - The cellular slime mold, Dictyostelium discoideum is a non-metazoan organism, yet
      we now demonstrate that a disintegrin domain-containing protein, the product of
      the ampA gene, plays a role in cell type specification. Disintegrin domain
      containing proteins are involved in Notch signaling in Drosophila and C. elegans
      via an ectodomain shedding mechanism that depends on a metalloprotease domain.
      The Dictyostelium protein lacks a metalloprotease domain. Nonetheless, analysis
      of cell type specific reporter gene expression during development of the ampA
      null strain identifies patterning defects that define two distinct roles for the
      AmpA protein in specifying cell fate. In the absence of a functional ampA gene,
      cells prematurely specify as prespore cells. Prestalk cell differentiation and
      migration are delayed. Both of these defects can be rescued by the inclusion of
      10% wild-type cells in the developing null mutant aggregates, indicating that the
      defect is non-cell autonomous. The ampA gene is also demonstrated to be necessary
      in a cell-autonomous manner for the correct localization of anterior-like cells
      to the upper cup of the fruiting body. When derived from ampA null cells, the
      anterior-like cells are unable to localize to positions in the interior of the
      developing mounds. Wild-type cells can rescue defects in morphogenesis by
      substituting for null cells when they differentiate as anterior-like cells, but
      they cannot rescue the ability of ampA null cells to fill this role. Thus, in
      spite of its simpler structure, the Dictyostelium ampA protein carries out the
      same diversity of functions that have been observed for the ADAM and ADAMTS
      families in metazoans.

PMID- 11973271
TI  - Context-dependent utilization of Notch activity in Drosophila glial
      determination.
AB  - During Drosophila neurogenesis, glial differentiation depends on the expression
      of glial cells missing (gcm). Understanding how glial fate is achieved thus
      requires knowledge of the temporal and spatial control mechanisms directing gcm
      expression. A recent report showed that in the adult bristle lineage, gcm
      expression is negatively regulated by Notch signaling ( Van De Bor, V. and
      Giangrande, A. (2001). Development 128, 1381-1390). Here we show that the effect
      of Notch activation on gliogenesis is context-dependent. In the dorsal bipolar
      dendritic (dbd) sensory lineage in the embryonic peripheral nervous system (PNS),
      asymmetric cell division of the dbd precursor produces a neuron and a glial cell,
      where gcm expression is activated in the glial daughter. Within the dbd lineage,
      Notch is specifically activated in one of the daughter cells and is required for
      gcm expression and a glial fate. Thus Notch activity has opposite consequences on
      gcm expression in two PNS lineages. Ectopic Notch activation can direct
      gliogenesis in a subset of embryonic PNS lineages, suggesting that Notch
      dependent gliogenesis is supported in certain developmental contexts. We present
      evidence that POU-domain protein Nubbin/PDM-1 is one of the factors that provide
      such context.

PMID- 11973272
TI  - The Arabidopsis ATK1 gene is required for spindle morphogenesis in male meiosis.
AB  - The spindle plays a central role in chromosome segregation during mitosis and
      meiosis. In particular, various kinesins are thought to play crucial roles in
      spindle structure and function in both mitosis and meiosis of fungi and animals.
      A group of putative kinesins has been previously identified in Arabidopsis,
      called ATK1-ATK4 (previously known as KATA-KATD), but their in vivo functions
      have not been tested with genetic studies. We report here the isolation and
      characterization of a mutant, atk1-1, which has a defective ATK1 gene. The atk1-1
      mutant was identified in a collection of Ds transposon insertion lines by its
      reduced fertility. Reciprocal crosses between the atk1-1 mutant and wild type
      showed that only male fertility was reduced, not female fertility. Molecular
      analyses, including revertant studies, indicated that the Ds insertion in the
      ATK1 gene was responsible for the fertility defect. Light microscopy revealed
      that, in the atk1-1 mutant, male meiosis was defective, producing an abnormal
      number of microspores of variable sizes. Further cytological studies indicated
      that meiotic chromosome segregation and spindle organization were both abnormal
      in the mutant. Specifically, the atk1-1 mutant male meiotic cells had spindles
      that were broad, unfocused and multi-axial at the poles at metaphase I, unlike
      the typical fusiform bipolar spindle found in the wild-type metaphase I cells.
      Therefore, the ATK1 gene plays a crucial role in spindle morphogenesis in male
      Arabidopsis meiosis.

PMID- 11973273
TI  - Repression of Teashirt marks the initiation of wing development.
AB  - The wing imaginal disc comprises the primordia of the adult wing and the dorsal
      thoracic body wall. During second larval instar, the wing disc is subdivided into
      distinct domains that correspond to the presumptive wing and body wall. Early
      activity of the signaling protein Wingless has been implicated in the
      specification of the wing primordium. Wingless mutants can produce animals in
      which the wing is replaced by a duplication of thoracic structures. Specification
      of wing fate has been visualized by expression of the POU-homeodomain protein
      Nubbin in the presumptive wing territory and by repression of the homeodomain
      protein Homothorax. We report that repression of the zinc-finger transcription
      factor Teashirt (Tsh) is the earliest event in wing specification. Repression of
      Tsh by the combined action of Wingless and Decapentaplegic is required for wing
      pouch formation and for subsequent repression of Hth. Thus, repression of Tsh
      defines the presumptive wing earlier in development than repression of Hth, which
      must therefore be considered a secondary event.

PMID- 11973274
TI  - The bric a brac locus consists of two paralogous genes encoding BTB/POZ domain
      proteins and acts as a homeotic and morphogenetic regulator of imaginal
      development in Drosophila.
AB  - The bric a brac (bab) locus acts as a homeotic and morphogenetic regulator in the
      development of ovaries, appendages and the abdomen. It consists of two
      structurally and functionally related genes, bab1 and bab2, each of which encodes
      a single nuclear protein. Bab1 and Bab2 have two conserved domains in common, a
      BTB/POZ domain and a Psq domain, a motif that characterizes a subfamily of
      BTB/POZ domain proteins in Drosophila. The tissue distribution of Bab1 and Bab2
      overlaps, with Bab1 being expressed in a subpattern of Bab2. Analysis of a series
      of mutations indicates that the two bab genes have synergistic, distinct and
      redundant functions during imaginal development. Interestingly, several
      reproduction-related traits that are sexually dimorphic or show diversity among
      Drosophila species are highly sensitive to changes in the bab gene dose,
      suggesting that alterations in bab activity may contribute to evolutionary
      modification of sex-related morphology.

PMID- 11973275
TI  - Co-ordinating retinal histogenesis: early cell cycle exit enhances early cell
      fate determination in the Xenopus retina.
AB  - The laminar arrays of distinct cell types in the vertebrate retina are built by a
      histogenic process in which cell fate is correlated with birth order. To explore
      this co-ordination mechanistically, we altered the relative timing of cell cycle
      exit in the developing Xenopus retina and asked whether this affected the
      activity of neural determinants. We found that Xath5, a bHLH proneural gene that
      promotes retinal ganglion cell (RGC) fate, ( Kanekar, S., Perron, M., Dorsky, R.,
      Harris, W. A., Jan, L. Y., Jan, Y. N. and Vetter, M. L. (1997) Neuron 19, 981
      994), does not cause these cells to be born prematurely. To drive cells out of
      the cell cycle early, therefore, we misexpressed the cyclin kinase inhibitor,
      p27Xic1. We found that early cell cycle exit potentiates the ability of Xath5 to
      promote RGC fate. Conversely, the cell cycle activator, cyclin E1, which inhibits
      cell cycle exit, biases Xath5-expressing cells toward later neuronal fates. We
      found that Notch activation in this system caused cells to exit the cell cycle
      prematurely, and when it is misexpressed with Xath5, it also potentiates the
      induction of RGCs. The potentiation is counteracted by co-expression of cyclin
      E1. These results suggest a model of histogenesis in which the activity of
      factors that promote early cell cycle exit enhances the activity of factors that
      promote early cellular fates.

PMID- 11973276
TI  - Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and
      are distinct from duct progenitors.
AB  - The location and lineage of cells that give rise to endocrine islets during
      embryogenesis has not been established nor has the origin or identity of adult
      islet stem cells. We have employed an inducible Cre-ER(TM)-LoxP system to
      indelibly mark the progeny of cells expressing either Ngn3 or Pdx1 at different
      stages of development. The results provide direct evidence that NGN3+ cells are
      islet progenitors during embryogenesis and in adult mice. In addition, we find
      that cells expressing Pdx1 give rise to all three types of pancreatic tissue:
      exocrine, endocrine and duct. Furthermore, exocrine and endocrine cells are
      derived from Pdx1-expressing progenitors throughout embryogenesis. By contrast,
      the pancreatic duct arises from PDX1+ progenitors that are set aside around
      embryonic day 10.5 (E9.5-E11.5). These findings suggest that lineages for
      exocrine, endocrine islet and duct progenitors are committed at mid-gestation.

PMID- 11973277
TI  - BMP signaling patterns the dorsal and intermediate neural tube via regulation of
      homeobox and helix-loop-helix transcription factors.
AB  - In the spinal neural tube, populations of neuronal precursors that express a
      unique combination of transcription factors give rise to specific classes of
      neurons at precise locations along the dorsoventral axis. Understanding the
      patterning mechanisms that generate restricted gene expression along the
      dorsoventral axis is therefore crucial to understanding the creation of diverse
      neural cell types. Bone morphogenetic proteins (BMPs) and other transforming
      growth factor beta (TGFbeta) proteins are expressed by the dorsal-most cells of
      the neural tube (the roofplate) and surrounding tissues, and evidence indicates
      that they play a role in assigning cell identity. We have manipulated the level
      of BMP signaling in the chicken neural tube to show that BMPs provide patterning
      information to both dorsal and intermediate cells. BMP regulation of the
      expression boundaries of the homeobox proteins Pax6, Dbx2 and Msx1 generates
      precursor populations with distinct developmental potentials. Within the
      resulting populations, thresholds of BMP act to set expression domain boundaries
      of developmental regulators of the homeobox and basic helix-loop-helix (bHLH)
      families, ultimately leading to the generation of a diversity of differentiated
      neural cell types. This evidence strongly suggests that BMPs are the key
      regulators of dorsal cell identity in the spinal neural tube.

PMID- 11973278
TI  - Hypomorphic Mesp allele distinguishes establishment of rostrocaudal polarity and
      segment border formation in somitogenesis.
AB  - A bHLH-type transcription factor, Mesp2, plays an essential role in somite
      segmentation in mice. Zebrafish mespb (mesp-b), a putative homologue of mouse
      Mesp2, is transiently expressed in the rostral presomitic mesoderm similarly to
      Mesp2. To determine whether zebrafish mespb is a functional homologue of mouse
      Mesp2, zebrafish mespb was introduced into the mouse Mesp2 locus by homologous
      recombination. Introduced mespb almost rescued the Mesp2 deficiency in the
      homozygous mespb knockin mouse, indicating that mespb is a functional homologue
      of mouse Mesp2. Segmented somites were clearly observed although the partial
      fusion of the vertebral columns still occurred. Interestingly, however, the
      nature and dosage of the mespb gene affected the rescue event. A mouse line,
      which has a hypomorphic Mesp2 allele generated by the introduction of neo-mespb,
      gave rise to an epithelial somite without normal rostrocaudal (RC) polarity. RC
      polarity was also lacking in the presomitic mesoderm. The defects in RC polarity
      were determined by the altered expressions of Uncx4.1 and Dll1 in the segmented
      somites and presomitic mesoderm, respectively. In contrast, the expression of
      EphA4 (Epha4), lunatic fringe or protocadherin, thought to be involved in segment
      border formation, was fairly normal in hypomorphic mutant embryos. These results
      suggest that the Mesp family of transcription factors is involved in both segment
      border formation and establishment of RC polarity through different genetic
      cascades.

PMID- 11973280
TI  - The role of Math1 in inner ear development: Uncoupling the establishment of the
      sensory primordium from hair cell fate determination.
AB  - During embryonic development of the inner ear, the sensory primordium that gives
      rise to the organ of Corti from within the cochlear epithelium is patterned into
      a stereotyped array of inner and outer sensory hair cells separated from each
      other by non-sensory supporting cells. Math1, a close homolog of the Drosophila
      proneural gene atonal, has been found to be both necessary and sufficient for the
      production of hair cells in the mouse inner ear. Our results indicate that Math1
      is not required to establish the postmitotic sensory primordium from which the
      cells of the organ of Corti arise, but instead is limited to a role in the
      selection and/or differentiation of sensory hair cells from within the
      established primordium. This is based on the observation that Math1 is only
      expressed after the appearance of a zone of non-proliferating cells that
      delineates the sensory primordium within the cochlear anlage. The expression of
      Math1 is limited to a subpopulation of cells within the sensory primordium that
      appear to differentiate exclusively into hair cells as the sensory epithelium
      matures and elongates through a process that probably involves radial
      intercalation of cells. Furthermore, mutation of Math1 does not affect the
      establishment of this postmitotic sensory primordium, even though the subsequent
      generation of hair cells is blocked in these mutants. Finally, in Math1 mutant
      embryos, a subpopulation of the cells within the sensory epithelium undergo
      apoptosis in a temporal gradient similar to the basal-to-apical gradient of hair
      cell differentiation that occurs in the cochlea of wild-type animals.

PMID- 11973279
TI  - The Drosophila trithorax protein is a coactivator required to prevent re
      establishment of polycomb silencing.
AB  - Polycomb group (PcG) and Trithorax (TRX) complexes assemble at Polycomb response
      elements (PREs) and maintain respectively the repressed and active state of
      homeotic genes. Although PcG and TRX complexes are distinct, their binding to
      some PRE fragments in vitro depends on GAGA motifs. GAGA factor
      immunoprecipitates with both complexes. In presence of a PRE, TRX stimulates
      expression and prevents the return of repression at later stages. When TRX levels
      are reduced, repression is re-established in inappropriate regions of imaginal
      discs, suggesting that TRX insufficiency impairs the epigenetic memory of the
      active state. Targeting a GAL-TRX fusion shows that TRX is a coactivator that
      stimulates expression of an active gene but cannot initiate expression by itself.
      Targeting a histone acetylase to a PRE does not affect embryonic silencing but
      causes a loss of memory in imaginal discs, suggesting that deacetylation is
      required to establish the memory of the repressed state.

PMID- 11973281
TI  - Sonic hedgehog and the molecular regulation of mouse neural tube closure.
AB  - Neural tube closure is a fundamental embryonic event whose molecular regulation
      is poorly understood. As mouse neurulation progresses along the spinal axis,
      there is a shift from midline neural plate bending to dorsolateral bending. Here,
      we show that midline bending is not essential for spinal closure since, in its
      absence, the neural tube can close by a 'default' mechanism involving
      dorsolateral bending, even at upper spinal levels. Midline and dorsolateral
      bending are regulated by mutually antagonistic signals from the notochord and
      surface ectoderm. Notochordal signaling induces midline bending and
      simultaneously inhibits dorsolateral bending. Sonic hedgehog is both necessary
      and sufficient to inhibit dorsolateral bending, but is neither necessary nor
      sufficient to induce midline bending, which seems likely to be regulated by
      another notochordal factor. Attachment of surface ectoderm cells to the neural
      plate is required for dorsolateral bending, which ensures neural tube closure in
      the absence of sonic hedgehog signaling.

PMID- 11973282
TI  - Interaction of LEAFY, AGAMOUS and TERMINAL FLOWER1 in maintaining floral meristem
      identity in Arabidopsis.
AB  - The Arabidopsis transcription factor LEAFY acts upstream of homeotic genes such
      as AGAMOUS to confer floral identity on meristems that arise after the transition
      to reproductive development. Compared to the genetic circuitry regulating the
      establishment of floral meristem identity, little is known about its maintenance.
      Previous experiments with leafy heterozygous plants and agamous mutants grown in
      conditions that reduce the floral inductive stimulus have shown that both genes
      are required to prevent reversion of floral to inflorescence meristems. Here, we
      present evidence that LEAFY maintains floral meristem identity independently of
      AGAMOUS, and that the primary role of LEAFY is either direct repression of shoot
      identity genes or repression of an intermediate factor that activates shoot
      identity genes. The latter conclusions were deduced from the phenotypes conferred
      by a gain-of-function transgene, LEAFY:VP16, that appears to act as a dominant
      negative, or antimorphic, allele during maintenance of floral meristem identity.
      These observations contrast with previous findings that LEAFY acts as a direct
      activator of floral homeotic genes, supporting the hypothesis that the
      transcriptional activity of LEAFY is dependent on specific co-regulators.

PMID- 11973283
TI  - A germline-specific gap junction protein required for survival of differentiating
      early germ cells.
AB  - Germ cells require intimate associations and signals from the surrounding somatic
      cells throughout gametogenesis. The zero population growth (zpg) locus of
      Drosophila encodes a germline-specific gap junction protein, Innexin 4, that is
      required for survival of differentiating early germ cells during gametogenesis in
      both sexes. Animals with a null mutation in zpg are viable but sterile and have
      tiny gonads. Adult zpg-null gonads contain small numbers of early germ cells,
      resembling stem cells or early spermatogonia or oogonia, but lack later stages of
      germ cell differentiation. In the male, Zpg protein localizes to the surface of
      spermatogonia, primarily on the sides adjacent to the somatic cyst cells. In the
      female, Zpg protein localizes to germ cell surfaces, both those adjacent to
      surrounding somatic cells and those adjacent to other germ cells. We propose that
      Zpg-containing gap junctional hemichannels in the germ cell plasma membrane may
      connect with hemichannels made of other innexin isoforms on adjacent somatic
      cells. Gap junctional intercellular communication via these channels may mediate
      passage of crucial small molecules or signals between germline and somatic
      support cells required for survival and differentiation of early germ cells in
      both sexes.

PMID- 11973284
TI  - Regulation of hair follicle development by the TNF signal ectodysplasin and its
      receptor Edar.
AB  - X-linked and autosomal forms of anhidrotic ectodermal dysplasia syndromes (HED)
      are characterized by deficient development of several ectodermal organs,
      including hair, teeth and exocrine glands. The recent cloning of the genes that
      underlie these syndromes, ectodysplasin (ED1) and the ectodysplasin A receptor
      (EDAR), and their identification as a novel TNF ligand-receptor pair suggested a
      role for TNF signaling in embryonic morphogenesis. In the mouse, the genes of the
      spontaneous mutations Tabby (Ta) and downless (dl) were identified as homologs of
      ED1 and EDAR, respectively. To gain insight into the function of this signaling
      pathway in development of skin and hair follicles, we analyzed the expression and
      regulation of Eda and Edar in wild type as well as Tabby and Lef1 mutant mouse
      embryos. We show that Eda and Edar expression is confined to the ectoderm and
      occurs in a pattern that suggests a role of ectodysplasin/Edar signaling in the
      interactions between the ectodermal compartments and the formation and function
      of hair placodes. By using skin explant cultures, we further show that this
      signaling pathway is intimately associated with interactions between the
      epithelial and mesenchymal tissues. We also find that Ta mutants lack completely
      the placodes of the first developing tylotrich hairs, and that they do not show
      patterned expression of placodal genes, including Bmp4, Lef1, Shh, Ptch and Edar,
      and the genes for beta-catenin and activin A. Finally, we identified activin as a
      mesenchymal signal that stimulates Edar expression and WNT as a signal that
      induces Eda expression, suggesting a hierarchy of distinct signaling pathways in
      the development of skin and hair follicles. In conclusion, we suggest that Eda
      and Edar are associated with the onset of ectodermal patterning and that
      ectodysplasin/edar signaling also regulates the morphogenesis of hair follicles.

PMID- 11973285
TI  - E. B. Lewis and the bithorax complex: part I.

PMID- 11973286
TI  - Dependence of epistasis on environment and mutation severity as revealed by in
      silico mutagenesis of phage t7.
AB  - Understanding how interactions among deleterious mutations affect fitness may
      shed light on a variety of fundamental biological phenomena, including the
      evolution of sex, the buffering of genetic variations, and the topography of
      fitness landscapes. It remains an open question under what conditions and to what
      extent such interactions may be synergistic or antagonistic. To address this
      question, we employed a computer model for the intracellular growth of
      bacteriophage T7. We created in silico 90,000 mutants of phage T7, each carrying
      from 1 to 30 mutations, and evaluated the fitness of each by simulating its
      growth cycle. The simulations sought to account for the severity of single
      deleterious mutations on T7 growth, as well as the effect of the resource
      environment on our fitness measures. We found that mildly deleterious mutations
      interacted synergistically in poor-resource environments but antagonistically in
      rich-resource environments. However, severely deleterious mutations always
      interacted antagonistically, irrespective of environment. These results suggest
      that synergistic epistasis may be difficult to experimentally distinguish from
      nonepistasis because its effects appear to be most pronounced when the effects of
      mutations on fitness are most challenging to measure. Our approach demonstrates
      how computer simulations of developmental processes can be used to quantitatively
      study genetic interactions at the population level.

PMID- 11973287
TI  - Estimation of effective population size of HIV-1 within a host: a pseudomaximum
      likelihood approach.
AB  - Using pseudomaximum-likelihood approaches to phylogenetic inference and
      coalescent theory, we develop a computationally tractable method of estimating
      effective population size from serially sampled viral data. We show that the
      variance of the maximum-likelihood estimator of effective population size depends
      on the serial sampling design only because internal node times on a coalescent
      genealogy can be better estimated with some designs than with others. Given the
      internal node times and the number of sequences sampled, the variance of the
      maximum-likelihood estimator is independent of the serial sampling design. We
      then estimate the effective size of the HIV-1 population within nine hosts. If we
      assume that the mutation rate is 2.5 x 10(-5) substitutions/generation and is the
      same in all patients, estimated generation lengths vary from 0.73 to 2.43
      days/generation and the mean (1.47) is similar to the generation lengths
      estimated by other researchers. If we assume that generation length is 1.47 days
      and is the same in all patients, mutation rate estimates vary from 1.52 x 10(-5)
      to 5.02 x 10(-5). Our results indicate that effective viral population size and
      evolutionary rate per year are negatively correlated among HIV-1 patients.

PMID- 11973288
TI  - Genetic and physical interactions between DPB11 and DDC1 in the yeast DNA damage
      response pathway.
AB  - DPB11 is essential for DNA replication and S/M checkpoint control in
      Saccharomyces cerevisiae. The Dpb11 protein contains four BRCT domains, which
      have been proposed to be involved in protein-protein interactions. To further
      investigate the regulation and function of Dpb11, a yeast two-hybrid screen was
      carried out to identify proteins that physically interact with Dpb11. One
      positive clone isolated from the screen encoded a carboxyl-terminal fragment of
      Ddc1 (339-612 aa). Ddc1 is a DNA damage checkpoint protein, which, together with
      Mec3 and Rad17, has been proposed to form a PCNA-like complex and acts upstream
      in the DNA damage checkpoint pathways. We further determined that the carboxyl
      region of Dpb11 is required for its interaction with Ddc1. DDC1 and DPB11 also
      interact genetically. The Deltaddc1 dpb11-1 double mutant is more UV and MMS
      sensitive than the Deltaddc1 or the dpb11-1 single mutants. Furthermore, the
      double mutant is more hydroxyurea sensitive and displayed a lower restrictive
      temperature than dpb11-1. These results suggest that DPB11 and DDC1 may function
      in the same or parallel pathways after DNA damage and that DDC1 may play a role
      in responding to replication defects.

PMID- 11973289
TI  - Different phenotypes in vivo are associated with ATPase motif mutations in
      Schizosaccharomyces pombe minichromosome maintenance proteins.
AB  - The six conserved MCM proteins are essential for normal DNA replication. They
      share a central core of homology that contains sequences related to DNA-dependent
      and AAA(+) ATPases. It has been suggested that the MCMs form a replicative
      helicase because a hexameric subcomplex formed by MCM4, -6, and -7 proteins has
      in vitro DNA helicase activity. To test whether ATPase and helicase activities
      are required for MCM protein function in vivo, we mutated conserved residues in
      the Walker A and Walker B motifs of MCM4, -6, and -7 and determined that
      equivalent mutations in these three proteins have different in vivo effects in
      fission yeast. Some mutations reported to abolish the in vitro helicase activity
      of the mouse MCM4/6/7 subcomplex do not affect the in vivo function of fission
      yeast MCM complex. Mutations of consensus CDK sites in Mcm4p and Mcm7p also have
      no phenotypic consequences. Co-immunoprecipitation analyses and in situ chromatin
      binding experiments were used to study the ability of the mutant Mcm4ps to
      associate with the other MCMs, localize to the nucleus, and bind to chromatin. We
      conclude that the role of ATP binding and hydrolysis is different for different
      MCM subunits.

PMID- 11973290
TI  - Evidence that the pre-mRNA splicing factor Clf1p plays a role in DNA replication
      in Saccharomyces cerevisiae.
AB  - Clf1p is an essential, highly conserved protein in S. cerevisiae that has been
      implicated in pre-mRNA splicing. Clf1p's ortholog in Drosophila, Crn, is required
      for normal cell proliferation. Cells depleted of Clf1p arrest primarily with
      large buds, a single nucleus, a 2C DNA content, and a short, intact mitotic
      spindle. We isolated temperature-sensitive clf1 mutants that exhibit similar
      mitotic defects when released to the restrictive temperature from an early S
      phase block. While these mutants also accumulate unspliced pre-mRNA at the
      restrictive temperature, the mitotic arrest does not appear to result from a
      failure to splice tubulin pre-mRNA. Moreover, the same mutants exhibit a delayed
      entry into S phase when released to the restrictive temperature from a G1 phase
      block. This delay could not be suppressed by disruption of the S-phase CDK
      inhibitor SIC1, suggesting that Clf1p is involved in DNA replication. Consistent
      with this possibility, we find that Clf1p (but not the mutant clf1p) interacts
      with the DNA replication initiation protein Orc2p in two-hybrid and co
      immunoprecipitation assays, that Clf1p preferentially associates with origins of
      DNA replication, and that this association is Orc2p dependent. These observations
      suggest that Clf1p plays a direct role in the initiation of DNA replication.

PMID- 11973292
TI  - Differential regulation of Saccharomyces cerevisiae phospholipase D in
      sporulation and Sec14-independent secretion.
AB  - Saccharomyces cerevisiae Spo14, a phosphatidylcholine-specific,
      phosphatidylinositol (4,5) bisphosphate-activated phospholipase D (PLD), is
      essential for meiosis and spore formation. Spo14 is also required for secretion
      in the absence of the phosphatidylinositol/phosphatidylcholine transfer protein
      Sec14 (i.e., Sec14-independent secretion). In sporulating cells Spo14 is
      phosphorylated and relocalized within the cell. In contrast, Spo14 does not
      relocalize and is not phosphorylated in Sec14-independent secretion. Analysis of
      a partially phosphatidylinositol (4,5) bisphosphate-activated Spo14 mutant,
      spo14(R894G), revealed that Spo14 function in Sec14-independent secretion, unlike
      the situation in meiosis, requires fully stimulated PLD activity. Consistent with
      the differential regulation of Spo14 function during sporulation and secretion,
      we isolated a mutant allele, spo14-S251P, the product of which is improperly
      phosphorylated and fails to relocalize and rescue the sporulation phenotype of
      homozygous spo14 diploids, but supports Sec14-independent secretion. Furthermore,
      we show that the N-terminal domain of Spo14 is both phosphorylated and sufficient
      for prospore membrane localization during sporulation. These data indicate that
      Spo14 phosphorylation and relocalization are essential for the process of
      sporulation, but dispensable for Sec14-independent secretion. Finally, we
      demonstrate that Spo14 phosphorylation and relocalization are initiated by
      nitrogen and glucose limitation and occur independently of the process of
      meiosis.

PMID- 11973291
TI  - Mutations that affect vacuole biogenesis inhibit proliferation of the endoplasmic
      reticulum in Saccharomyces cerevisiae.
AB  - In yeast, increased levels of the sterol biosynthetic enzyme, 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase isozyme, Hmg1p, induce assembly of
      nuclear-associated ER membranes called karmellae. To identify additional genes
      involved in karmellae assembly, we screened temperature-sensitive mutants for
      karmellae assembly defects. Two independently isolated, temperature-sensitive
      strains that were also defective for karmellae biogenesis carried mutations in
      VPS16, a gene involved in vacuolar protein sorting. Karmellae biogenesis was
      defective in all 13 other vacuole biogenesis mutants tested, although the
      severity of the karmellae assembly defect varied depending on the particular
      mutation. The hypersensitivity of 14 vacuole biogenesis mutants to tunicamycin
      was well correlated with pronounced defects in karmellae assembly, suggesting
      that the karmellae assembly defect reflected alteration of ER structure or
      function. Consistent with this hypothesis, seven of eight mutations causing
      defects in secretion also affected karmellae assembly. However, the vacuole
      biogenesis mutants were able to proliferate their ER in response to Hmg2p,
      indicating that the mutants did not have a global defect in the process of ER
      biogenesis.

PMID- 11973293
TI  - A novel selection system for chromosome translocations in Saccharomyces
      cerevisiae.
AB  - Chromosomal translocations are common genetic abnormalities found in both
      leukemias and solid tumors. While much has been learned about the effects of
      specific translocations on cell proliferation, much less is known about what
      causes these chromosome rearrangements. This article describes the development
      and use of a system that genetically selects for rare translocation events using
      the yeast Saccharomyces cerevisiae. A translocation YAC was created that contains
      the breakpoint cluster region from the human MLL gene, a gene frequently involved
      in translocations in leukemia patients, flanked by positive and negative
      selection markers. A translocation between the YAC and a yeast chromosome, whose
      breakpoint falls within the MLL DNA, physically separates the markers and forms
      the basis for the selection. When RAD52 is deleted, essentially all of the
      selected and screened cells contain simple translocations. The detectable
      translocation rates are the same in haploids and diploids, although the
      mechanisms involved and true translocation rates may be distinct. A unique double
      strand break induced within the MLL sequences increases the number of detectable
      translocation events 100- to 1000-fold. This novel system provides a tractable
      assay for answering basic mechanistic questions about the development of
      chromosomal translocations.

PMID- 11973296
TI  - Domains of gene silencing near the left end of chromosome III in Saccharomyces
      cerevisiae.
AB  - In Saccharomyces cerevisiae the HM loci and regions adjacent to the telomeres are
      transcriptionally silent. HML is situated 11 kb from the left telomere of
      chromosome III. I have systematically examined gene silencing along this 11-kb
      chromosomal region. I found that silencing extends at least 1.1 kb beyond HML,
      indicating that the HML E silencer acts on both sides. Moreover, I obtained
      evidence indicating that a 0.71-kb sequence near the E silencer acts as a barrier
      to the spread of silencing and coincides with the left boundary of the silent HML
      domain. I also showed that silencing at the telomere is limited to an
      approximately 2-kb domain. On the other hand, an approximately 7-kb region
      between HML and the telomere is not silenced by HML or the telomere. These
      results provide a clear example of organization of the eukaryotic genome into
      interspersed domains with distinct potentials for gene expression.

PMID- 11973294
TI  - A role for histone H2B during repair of UV-induced DNA damage in Saccharomyces
      cerevisiae.
AB  - To investigate the role of the nucleosome during repair of DNA damage in yeast,
      we screened for histone H2B mutants that were sensitive to UV irradiation. We
      have isolated a new mutant, htb1-3, that shows preferential sensitivity to UV-C.
      There is no detectable difference in bulk chromatin structure or in the number of
      UV-induced cis-syn cyclobutane pyrimidine dimers (CPD) between HTB1 and htb1-3
      strains. These results suggest a specific effect of this histone H2B mutation in
      UV-induced DNA repair processes rather than a global effect on chromatin
      structure. We analyzed the UV sensitivity of double mutants that contained the
      htb1-3 mutation and mutations in genes from each of the three epistasis groups of
      RAD genes. The htb1-3 mutation enhanced UV-induced cell killing in rad1Delta and
      rad52Delta mutants but not in rad6Delta or rad18Delta mutants, which are
      defective in postreplicational DNA repair (PRR). When combined with other
      mutations that affect PRR, the histone mutation increased the UV sensitivity of
      strains with defects in either the error-prone (rev1Delta) or error-free
      (rad30Delta) branches of PRR, but did not enhance the UV sensitivity of a strain
      with a rad5Delta mutation. When combined with a ubc13Delta mutation, which is
      also epistatic with rad5Delta, the htb1-3 mutation enhanced UV-induced cell
      killing. These results suggest that histone H2B acts in a novel RAD5-dependent
      branch of PRR.

PMID- 11973295
TI  - The mitochondrial nucleoid protein, Mgm101p, of Saccharomyces cerevisiae is
      involved in the maintenance of rho(+) and ori/rep-devoid petite genomes but is
      not required for hypersuppressive rho(-) mtDNA.
AB  - The Saccharomyces cerevisiae MGM101 gene encodes a DNA-binding protein targeted
      to mitochondrial nucleoids. MGM101 is essential for maintenance of a functional
      rho(+) genome because meiotic segregants, with a disrupted mgm101 allele, cannot
      undergo more than 10 divisions on glycerol medium. Quantitative analysis of mtDNA
      copy number in a rho(+) strain carrying a temperature-sensitive allele, mgm101-1,
      revealed that the amount of mtDNA is halved each cell division upon a shift to
      the restrictive temperature. These data suggest that mtDNA replication is rapidly
      blocked in cells lacking MGM101. However, a small proportion of meiotic
      segregants, disrupted in MGM101, have rho(-) genomes that are stably maintained.
      Interestingly, all surviving rho(-) mtDNAs contain an ori/rep sequence.
      Disruption of MGM101 in hypersuppressive (HS) strains does not have a significant
      effect on the propagation of HS rho(-) mtDNA. However, in petites lacking an
      ori/rep, disruption of MGM101 leads to either a complete loss or a dramatically
      decreased stability of mtDNA. This discriminatory effect of MGM101 suggests that
      replication of rho(+) and ori/rep-devoid rho(-) mtDNAs is carried out by the same
      process. By contrast, the persistence of ori/rep-containing mtDNA in HS petites
      lacking MGM101 identifies a distinct replication pathway. The alternative mtDNA
      replication mechanism provided by ori/rep is independent of mitochondrial RNA
      polymerase encoded by RPO41 as a HS rho(-) genome is stably maintained in a
      mgm101, rpo41 double mutant.

PMID- 11973297
TI  - Pol32, a subunit of Saccharomyces cerevisiae DNA polymerase delta, suppresses
      genomic deletions and is involved in the mutagenic bypass pathway.
AB  - The Pol32 subunit of S. cerevisiae DNA polymerase (Pol) delta plays an important
      role in replication and mutagenesis. Here, by measuring the CAN1 forward mutation
      rate, we found that either POL32 or REV3 (which encodes the Pol zeta catalytic
      subunit) inactivation produces overlapping antimutator effects against rad
      mutators belonging to three epistasis groups. In contrast, the msh2Delta
      pol32Delta double mutant exhibits a synergistic mutator phenotype. Can(r)
      mutation spectrum analysis of pol32Delta strains revealed a substantial increase
      in the frequency of deletions and duplications (primarily deletions) of sequences
      flanked by short direct repeats, which appears to be RAD52 and RAD10 independent.
      To better understand the pol32Delta and rev3Delta antimutator effects in rad
      backgrounds and the pol32Delta mutator effect in a msh2Delta background, we
      determined Can(r) mutation spectra for rad5Delta, rad5Delta pol32Delta, rad5Delta
      rev3Delta, msh2Delta, msh2Delta pol32Delta, and msh2Delta rev3Delta strains. Both
      rad5Delta pol32Delta and rad5Delta rev3Delta mutants exhibit a reduction in
      frameshifts and base substitutions, attributable to antimutator effects conferred
      by the pol32Delta and rev3Delta mutations. In contrast, an increase in these two
      types of alterations is attributable to a synergistic mutator effect between the
      pol32Delta and msh2Delta mutations. Taken together, these observations indicate
      that Pol32 is important in ensuring genome stability and in mutagenesis.

PMID- 11973299
TI  - Ady3p links spindle pole body function to spore wall synthesis in Saccharomyces
      cerevisiae.
AB  - Spore formation in Saccharomyces cerevisiae requires the de novo synthesis of
      prospore membranes and spore walls. Ady3p has been identified as an interaction
      partner for Mpc70p/Spo21p, a meiosis-specific component of the outer plaque of
      the spindle pole body (SPB) that is required for prospore membrane formation, and
      for Don1p, which forms a ring-like structure at the leading edge of the prospore
      membrane during meiosis II. ADY3 expression has been shown to be induced in
      midsporulation. We report here that Ady3p interacts with additional components of
      the outer and central plaques of the SPB in the two-hybrid assay. Cells that lack
      ADY3 display a decrease in sporulation efficiency, and most ady3Delta/ady3Delta
      asci that do form contain fewer than four spores. The sporulation defect in
      ady3Delta/ady3Delta cells is due to a failure to synthesize spore wall polymers.
      Ady3p forms ring-like structures around meiosis II spindles that colocalize with
      those formed by Don1p, and Don1p rings are absent during meiosis II in
      ady3Delta/ady3Delta cells. In mpc70Delta/mpc70Delta cells, Ady3p remains
      associated with SPBs during meiosis II. Our results suggest that Ady3p mediates
      assembly of the Don1p-containing structure at the leading edge of the prospore
      membrane via interaction with components of the SPB and that this structure is
      involved in spore wall formation.

PMID- 11973300
TI  - A genetic map of Gibberella zeae (Fusarium graminearum).
AB  - We constructed a genetic linkage map of Gibberella zeae (Fusarium graminearum) by
      crossing complementary nitrate-nonutilizing (nit) mutants of G. zeae strains R
      5470 (from Japan) and Z-3639 (from Kansas). We selected 99 nitrate-utilizing
      (recombinant) progeny and analyzed them for amplified fragment length
      polymorphisms (AFLPs). We used 34 pairs of two-base selective AFLP primers and
      identified 1048 polymorphic markers that mapped to 468 unique loci on nine
      linkage groups. The total map length is approximately 1300 cM with an average
      interval of 2.8 map units between loci. Three of the nine linkage groups contain
      regions in which there are high levels of segregation distortion. Selection for
      the nitrate-utilizing recombinant progeny can explain two of the three skewed
      regions. Two linkage groups have recombination patterns that are consistent with
      the presence of intercalary inversions. Loci governing trichothecene toxin amount
      and type (deoxynivalenol or nivalenol) map on linkage groups IV and I,
      respectively. The locus governing the type of trichothecene produced (nivalenol
      or deoxynivalenol) cosegregated with the TRI5 gene (which encodes trichodiene
      synthase) and probably maps in the trichothecene gene cluster. This linkage map
      will be useful in population genetic studies, in map-based cloning, for QTL
      (quantitative trait loci) analysis, for ordering genomic libraries, and for
      genomic comparisons of related species.

PMID- 11973301
TI  - Evidence for interaction of Schizophyllum commune Y mating-type proteins in vivo.
AB  - The Aalpha mating-type locus of Schizophyllum commune regulates sexual
      development and contains the code for two proteins, Y and Z, which are thought to
      form a complex and function as a transcription factor. Import of these proteins
      into the nucleus may be an essential step in Aalpha-regulated sexual development.
      The Y proteins contain a bipartite basic sequence, which is an excellent
      candidate for a nuclear localization sequence (NLS), while Z proteins contain no
      such sequence. Here we describe experiments in which deletions were made in the
      putative NLS sequence of Y4. We show that this putative NLS is essential to the
      function of the Y protein and capable of mislocalizing green fluorescent protein
      (GFP) to the nucleus in Saccharomyces cerevisiae. Further, we describe genetic
      experiments that demonstrate the first Y-Y protein interactions in vivo. These
      results are consistent with our previously postulated hypothesis that the Y-Z
      complex is likely to be of a higher order than dimer.

PMID- 11973298
TI  - Protein phosphatase type 1 regulates ion homeostasis in Saccharomyces cerevisiae.
AB  - Protein phosphatase type 1 (PP1) is encoded by the essential gene GLC7 in
      Saccharomyces cerevisiae. glc7-109 (K259A, R260A) has a dominant, hyperglycogen
      defect and a recessive, ion and drug sensitivity. Surprisingly, the hyperglycogen
      phenotype is partially retained in null mutants of GAC1, GIP2, and PIG1, which
      encode potential glycogen-targeting subunits of Glc7. The R260A substitution in
      GLC7 is responsible for the dominant and recessive traits of glc7-109. Another
      mutation at this residue, glc7-R260P, confers only salt sensitivity, indicating
      that the glycogen and salt traits of glc7-109 are due to defects in distinct
      physiological pathways. The glc7-109 mutant is sensitive to cations,
      aminoglycosides, and alkaline pH and exhibits increased rates of l-leucine and
      3,3'-dihexyloxacarbocyanine iodide uptake, but it is resistant to molar
      concentrations of sorbitol or KCl, indicating that it has normal osmoregulation.
      KCl suppresses the ion and drug sensitivities of the glc7-109 mutant. The CsCl
      sensitivity of this mutant is suppressed by recessive mutations in PMA1, which
      encodes the essential plasma membrane H(+)ATPase. Together, these results
      indicate that Glc7 regulates ion homeostasis by controlling ion transport and/or
      plasma membrane potential, a new role for Glc7 in budding yeast.

PMID- 11973302
TI  - Polymorphism and selection at the SerH immobilization antigen locus in natural
      populations of Tetrahymena thermophila.
AB  - The SerH locus of Tetrahymena thermophila is one of several paralogous loci with
      genes encoding variants of the major cell surface protein known as the
      immobilization antigen (i-ag). The locus is highly polymorphic, raising questions
      concerning functional equivalency and selective forces acting on its multiple
      alleles. Here, we compare the sequences and expression of SerH1, SerH3, SerH4,
      SerH5, and SerH6. The precursor i-ags are highly similar. They are rich in
      alanine, serine, threonine, and cysteine and they share nearly identical ER
      translocation and GPI addition signals. The locations of the 39 cysteines are
      highly conserved, particularly in the 3.5 central, imperfect tandem repeats in
      which 8 periodic cysteines punctuate alternating short and long stretches of
      amino acids. Hydrophobicity patterns are also conserved. Nevertheless, amino acid
      sequence identity is low, ranging from 60.7 to 82.9%. At the nucleotide level,
      from 9.7 to 26.7% of nucleotide sites are polymorphic in pairwise comparisons.
      Expression of each allele is regulated by temperature-sensitive mRNA stability. H
      mRNAs are stable at <36 degrees but are unstable at >36 degrees. The H5 mRNA,
      which is less affected by temperature, has a different arrangement of the
      putative mRNA destabilization motif AUUUA. Statistical analysis of SerH genes
      indicates that the multiple alleles are neutral. Significantly low ratios of the
      rates of nonsynonymous to synonymous amino acid substitutions suggest that the
      multiple alleles are subject to purifying (negative) selection enforcing
      constraints on structure.

PMID- 11973303
TI  - Trans-splicing as a novel mechanism to explain interallelic complementation in
      Drosophila.
AB  - Two mutant alleles of the same gene, each located in one of the two homologous
      chromosomes, may in some instances restore the wild-type function of the gene.
      This is the case with certain combinations of mutant alleles in the mod(mdg4)
      gene. This gene encodes several different proteins, including Mod(mdg4)2.2, a
      component of the gypsy insulator. This protein is encoded by two separate
      transcription units that can be combined in a trans-splicing reaction to form the
      mature Mod(mdg4)2.2-encoding RNA. Molecular characterization of complementing
      alleles shows that they affect the two different transcription units. Flies
      homozygous for each allele are missing the Mod(mdg4)2.2 protein, whereas wild
      type trans-heterozygotes are able to synthesize almost normal levels of the
      Mod(mdg4)2.2 product. This protein is functional as judged by its ability to form
      a functional insulator complex. The results suggest that the interallelic
      complementation in the mod(mdg4) gene is a consequence of trans-splicing between
      two different mutant transcripts. A conclusion from this observation is that the
      trans-splicing reaction that takes place between transcripts produced on two
      different mutant chromosomes ensures wild-type levels of functional protein.

PMID- 11973304
TI  - subito encodes a kinesin-like protein required for meiotic spindle pole formation
      in Drosophila melanogaster.
AB  - The female meiotic spindle lacks a centrosome or microtubule-organizing center in
      many organisms. During cell division, these spindles are organized by the
      chromosomes and microtubule-associated proteins. Previous studies in Drosophila
      melanogaster implicated at least one kinesin motor protein, NCD, in tapering the
      microtubules into a bipolar spindle. We have identified a second Drosophila
      kinesin-like protein, SUB, that is required for meiotic spindle function. At
      meiosis I in males and females, sub mutations affect only the segregation of
      homologous chromosomes. In female meiosis, sub mutations have a similar phenotype
      to ncd; even though chromosomes are joined by chiasmata they fail to segregate at
      meiosis I. Cytological analyses have revealed that sub is required for bipolar
      spindle formation. In sub mutations, we observed spindles that were unipolar,
      multipolar, or frayed with no defined poles. On the basis of these phenotypes and
      the observation that sub mutations genetically interact with ncd, we propose that
      SUB is one member of a group of microtubule-associated proteins required for
      bipolar spindle assembly in the absence of the centrosomes. sub is also required
      for the early embryonic divisions but is otherwise dispensable for most mitotic
      divisions.

PMID- 11973305
TI  - Genetic analysis of Drosophila melanogaster polytene chromosome region 44D-45F:
      loci required for viability and fertility.
AB  - A genetic screen to identify mutations in genes in the 45A region on the right
      arm of chromosome 2 that are involved in oogenesis in Drosophila was undertaken.
      Several lethal but no female sterile mutations in the region had previously been
      identified in screens for P-element insertion or utilizing X rays or EMS as a
      mutagen. Here we report the identification of EMS-induced mutations in 21
      essential loci in the 45D-45F region, including 13 previously unidentified loci.
      In addition, we isolated three mutant alleles of a newly identified locus
      required for fertility, sine prole. Mutations in sine prole disrupt
      spermatogenesis at or before individualization of spermatozoa and cause multiple
      defects in oogenesis, including inappropriate division of the germline cyst and
      arrest of oogenesis at stage 4.

PMID- 11973306
TI  - Mutations in the midway gene disrupt a Drosophila acyl coenzyme A: diacylglycerol
      acyltransferase.
AB  - During Drosophila oogenesis, defective or unwanted egg chambers are eliminated
      during mid-oogenesis by programmed cell death. In addition, final cytoplasm
      transport from nurse cells to the oocyte depends upon apoptosis of the nurse
      cells. To study the regulation of germline apoptosis, we analyzed the midway
      mutant, in which egg chambers undergo premature nurse cell death and
      degeneration. The midway gene encodes a protein similar to mammalian acyl
      coenzyme A: diacylglycerol acyltransferase (DGAT), which converts diacylglycerol
      (DAG) into triacylglycerol (TAG). midway mutant egg chambers contain severely
      reduced levels of neutral lipids in the germline. Expression of midway in insect
      cells results in high levels of DGAT activity in vitro. These results show that
      midway encodes a functional DGAT and that changes in acylglycerol lipid
      metabolism disrupt normal egg chamber development in Drosophila.

PMID- 11973307
TI  - Novel putative nicotinic acetylcholine receptor subunit genes, Dalpha5, Dalpha6
      and Dalpha7, in Drosophila melanogaster identify a new and highly conserved
      target of adenosine deaminase acting on RNA-mediated A-to-I pre-mRNA editing.
AB  - Genome analysis of the fruit fly Drosophila melanogaster reveals three new ligand
      gated ion channel subunits with the characteristic YXCC motif found only in alpha
      type nicotinic acetylcholine receptor subunits. The subunits are designated
      Dalpha5, Dalpha6, and Dalpha7. Cloning of the Dalpha5 embryonic cDNAs reveals an
      atypically large N terminus, part of which is without identifiable sequence
      motifs and is specified by two polymorphic alleles. Embryonic clones from Dalpha6
      contain multiple variant transcripts arising from alternative splicing as well as
      A-to-I pre-mRNA editing. Alternative splicing in Dalpha6 involves exons encoding
      nAChR functional domains. The Dalpha6 transcript is a target of the Drosophila
      adenosine deaminase acting on RNA (dADAR). This is the first case for any
      organism where a nAChR gene is the target of mRNA editing. Seven adenosines could
      be modified in the extracellular ligand-binding region of Dalpha6, four of which
      are also edited in the Dalpha6 ortholog in the tobacco budworm Heliothis
      virescens. The conservation of an editing site between the insect orders Diptera
      and Lepidoptera makes nAChR editing the most evolutionarily conserved
      invertebrate RNA editing site so far described. These findings add to our
      understanding of nAChR subunit diversity, which is increased and regulated by
      mechanisms acting at the genomic and mRNA levels.

PMID- 11973308
TI  - The function of the frizzled pathway in the Drosophila wing is dependent on
      inturned and fuzzy.
AB  - The Drosophila epidermis is characterized by a dramatic planar or tissue
      polarity. The frizzled pathway has been shown to be a key regulator of planar
      polarity for hairs on the wing, ommatidia in the eye, and sensory bristles on the
      notum. We have investigated the genetic relationships between putative frizzled
      pathway downstream genes inturned, fuzzy, and multiple wing hairs (inturned-like
      genes) and upstream genes such as frizzled, prickle, and starry night (frizzled
      like genes). Previous data showed that the inturned-like genes were epistatic to
      the frizzled-like genes when the entire wing was mutant. We extended those
      experiments and examined the behavior of frizzled clones in mutant wings. We
      found the domineering nonautonomy of frizzled clones was not altered when the
      clone cells were simultaneously mutant for inturned, multiple wing hairs, or
      dishevelled but it was blocked when the entire wing was mutant for inturned,
      fuzzy, multiple wing hairs, or dishevelled. Thus, for the domineering nonautonomy
      phenotype of frizzled, inturned and multiple wing hairs are needed in the
      responding cells but not in the clone itself. Expressing a number of frizzled
      pathway genes in a gradient across part of the wing repolarizes wing cells in
      that region. We found inturned, fuzzy, and multiple wing hairs were required for
      a gradient of frizzled, starry night, prickle, or spiny-legs expression to
      repolarize wing cells. These data argue that inturned, fuzzy, and multiple wing
      hairs are downstream components of the frizzled pathway. To further probe the
      relationship between the frizzled-like and inturned-like genes we determined the
      consequences of altering the activity of frizzled-like genes in wings that
      carried weak alleles of inturned or fuzzy. Interestingly, both increasing and
      decreasing the activity of frizzled and other upstream genes enhanced the
      phenotypes of hypomorphic inturned and fuzzy mutants. We also examined the
      relationship between the frizzled-like and inturned-like genes in other regions
      of the fly. For some body regions and cell types (e.g., abdomen) the inturned
      like genes were epistatic to the frizzled-like genes, but in other body regions
      (e.g., eye) that was not the case. Thus, the genetic control of tissue polarity
      is body region specific.

PMID- 11973309
TI  - The gypsy insulators flanking yellow enhancers do not form a separate
      transcriptional domain in Drosophila melanogaster: the enhancers can activate an
      isolated yellow promoter.
AB  - The best-characterized insulator in Drosophila melanogaster is the Su(Hw)-binding
      region contained within the gypsy retrotransposon. In the y(2) mutant, Su(Hw)
      protein partially inhibits yellow transcription by blocking the function of
      transcriptional enhancers located distally from the yellow promoter with respect
      to gypsy. Previously we have shown that yellow enhancers can overcome inhibition
      by a downstream insulator in the y(rh1) allele, when a second gypsy element is
      located upstream of the enhancers. To understand how two insulators neutralize
      each other, we isolated various deletions that terminate in the regulatory region
      of the y(rh1) allele. To generate these alleles we used DNA elongation by gene
      conversion of the truncated chromosomes at the end of the yellow regulatory
      region. We found that gypsy insulator can function at the end of the truncated
      chromosome. Addition of the gypsy insulator upstream of the yellow enhancers
      overcomes the enhancer-blocking activity of the gypsy insulator inserted between
      the yellow enhancers and promoter. These results suggest that the gypsy
      insulators do not form separate transcriptional domains that delimit the
      interactions between enhancers and promoters.

PMID- 11973310
TI  - A complex array of DNA-binding proteins required for pairing-sensitive silencing
      by a polycomb group response element from the Drosophila engrailed gene.
AB  - Regulatory DNA from the Drosophila gene engrailed causes silencing of a linked
      reporter gene (mini-white) in transgenic Drosophila. This silencing is
      strengthened in flies homozygous for the transgene and has been called "pairing
      sensitive silencing." The pairing-sensitive silencing activities of a large
      fragment (2.6 kb) and a small subfragment (181 bp) were explored. Since pairing
      sensitive silencing is often associated with Polycomb group response elements
      (PREs), we tested the activities of each of these engrailed fragments in a
      construct designed to detect PRE activity in embryos. Both fragments were found
      to behave as PREs in a bxd-Ubx-lacZ reporter construct, while the larger fragment
      showed additional silencing capabilities. Using the mini-white reporter gene, a
      139-bp minimal pairing-sensitive element (PSE) was defined. DNA mobility-shift
      assays using Drosophila nuclear extracts suggested that there are eight protein
      binding sites within this 139-bp element. Mutational analysis showed that at
      least five of these sites are important for pairing-sensitive silencing. One of
      the required sites is for the Polycomb group protein Pleiohomeotic and another is
      GAGAG, a sequence bound by the proteins GAGA factor and Pipsqueak. The identity
      of the other proteins is unknown. These data suggest a surprising degree of
      complexity in the DNA-binding proteins required for PSE function.

PMID- 11973311
TI  - Analysis of quantitative trait locus effects on the size and shape of mandibular
      molars in mice.
AB  - While >50 genes have been found to influence the development of teeth in mice, we
      still know very little about the genetic basis for the adaptive characteristics
      of teeth, such as size and shape. We applied interval mapping procedures to
      Procrustes size and shape data obtained from 10 morphological landmarks on the
      mandibular molar row of the F(2) progeny from a cross between the LG/J and SM/J
      strains of mice. This revealed many more QTL for molar shape (18) than for molar
      centroid size (3), although levels of dominance effects were comparable among QTL
      for size and shape. Comparisons of patterns of Procrustes additive and dominance
      shape effects and ordination of QTL effects by principal components analysis
      suggested that the effects of the shape QTL were dispersed among the three molars
      and thus that none of these molars represents a genetically distinct
      developmental structure. The results of an analysis of co-occurrence of QTL for
      molar shape, mandible shape, and cranial dimensions in these mice suggested that
      many of the QTL for molar shape may be the same as those affecting these other
      sets of characters, although in some cases this could be due to effects of
      closely linked genes.

PMID- 11973314
TI  - Simultaneous detection and fine mapping of quantitative trait loci in mice using
      heterogeneous stocks.
AB  - We describe a method to simultaneously detect and fine map quantitative trait
      loci (QTL) that is especially suited to the mapping of modifier loci in mouse
      mutant models. The method exploits the high level of historical recombination
      present in a heterogeneous stock (HS), an outbred population of mice derived from
      known founder strains. The experimental design is an F(2) cross between the HS
      and a genetically distinct line, such as one carrying a knockout or transgene.
      QTL detection is performed by a standard genome scan with approximately 100
      markers and fine mapping by typing the same animals using densely spaced markers
      over those candidate regions detected by the scan. The analysis uses an extension
      of the dynamic-programming technique employed previously to fine map QTL in HS
      mice. We show by simulation that a QTL accounting for 5% of the total variance
      can be detected and fine mapped with >50% probability to within 3 cM by
      genotyping approximately 1500 animals.

PMID- 11973312
TI  - A deer (subfamily Cervinae) genetic linkage map and the evolution of ruminant
      genomes.
AB  - Comparative maps between ruminant species and humans are increasingly important
      tools for the discovery of genes underlying economically important traits. In
      this article we present a primary linkage map of the deer genome derived from an
      interspecies hybrid between red deer (Cervus elaphus) and Pere David's deer
      (Elaphurus davidianus). The map is approximately 2500 cM long and contains >600
      markers including both evolutionary conserved type I markers and highly
      polymorphic type II markers (microsatellites). Comparative mapping by annotation
      and sequence similarity (COMPASS) was demonstrated to be a useful tool for
      mapping bovine and ovine ESTs in deer. Using marker order as a phylogenetic
      character and comparative map information from human, mouse, deer, cattle, and
      sheep, we reconstructed the karyotype of the ancestral Pecoran mammal and
      identified the chromosome rearrangements that have occurred in the sheep, cattle,
      and deer lineages. The deer map and interspecies hybrid pedigrees described here
      are a valuable resource for (1) predicting the location of orthologs to human
      genes in ruminants, (2) mapping QTL in farmed and wild deer populations, and (3)
      ruminant phylogenetic studies.

PMID- 11973313
TI  - A phenotype-sensitizing Apoe-deficient genetic background reveals novel
      atherosclerosis predisposition loci in the mouse.
AB  - Therapeutic intervention for atherosclerosis has predominantly concentrated on
      regulating cholesterol levels; however, these therapeutics are not efficacious
      for all patients, suggesting that other factors are involved. This study was
      initiated to identify mechanisms that regulate atherosclerosis predisposition in
      mice other than cholesterol level regulation. To do so we performed quantitative
      trait locus analysis using two inbred strains that each carry the atherosclerosis
      phenotype-sensitizing Apoe deficiency and that have been shown to have widely
      disparate predilection to atherosclerotic lesion formation. One highly
      significant locus on chromosome 10 (LOD = 7.8) accounted for 19% of the variance
      in lesion area independent of cholesterol. Two additional suggestive loci were
      identified on chromosomes 14 (LOD = 3.2) and 19 (LOD = 3.2), each accounting for
      7-8% of the lesion variance. In all, five statistically significant and
      suggestive loci affecting lesion size but not lipoprotein levels were identified.
      Many of these were recapitulated in an independent confirmatory cross. In
      summary, two independently performed crosses between C57BL/6 and FVB/N Apoe
      deficient mice have revealed several previously unreported atherosclerosis
      susceptibility loci that are distinct from loci linked to lipoprotein levels.

PMID- 11973315
TI  - Mitochondrial DNA heteroplasmy in wheat, Aegilops and their nucleus-cytoplasm
      hybrids.
AB  - A mitochondrial (mt) transcriptional unit, nad3-orf156, was studied in the
      nucleus-cytoplasm hybrids of wheat with D/D2 plasmons from Aegilops species and
      their parental lines. A comparative RFLP analysis and sequencing of the random
      PCR clones revealed the presence of seven sequence types and their polymorphic
      sites were mapped. All the hybrids possessed the paternal copies besides the
      maternal copies. More paternal copies were present in the D2 plasmon hybrids,
      whereas more maternal copies were present in the D plasmon hybrids. Two major
      copies were present with different stoichiometries in the maternal Aegilops
      parents. However, only a major D plasmon copy was detected in the hybrids,
      irrespective of their plasmon types. The hexaploid wheat parent (AABBDD genome)
      possessed the major D plasmon copy in approximately 5% stoichiometry, while no D
      plasmon-homologous copies were detected in the tetraploid wheat parent (AABB
      genome). The results suggest that the observed mtDNA heteroplasmy is due to
      paternal contribution of mtDNA. The different copy stoichiometry suggests
      differential amplification of the heteroplasmic copies among the hybrids and the
      parental lines. All editing sites and their editing frequencies were conserved
      among the lines, and only the maternal pattern of editing occurred in the
      hybrids.

PMID- 11973316
TI  - Crossover interference in Arabidopsis.
AB  - The crossover distribution in meiotic tetrads of Arabidopsis thaliana differs
      from those previously described for Drosophila and Neurospora. Whereas a chi
      square distribution with an even number of degrees of freedom provides a good fit
      for the latter organisms, the fit for Arabidopsis was substantially improved by
      assuming an additional set of crossovers sprinkled, at random, among those
      distributed as per chi square. This result is compatible with the view that
      Arabidopsis has two pathways for meiotic crossing over, only one of which is
      subject to interference. The results further suggest that Arabidopsis meiosis has
      >10 times as many double-strand breaks as crossovers.

PMID- 11973318
TI  - Gene loss, silencing and activation in a newly synthesized wheat allotetraploid.
AB  - We analyzed the events that affect gene structure and expression in the early
      stages of allopolyploidy in wheat. The transcriptome response was studied by
      analyzing 3072 transcripts in the first generation of a synthetic allotetraploid
      (genome S(l)S(l)A(m)A(m)), which resembles tetraploid wheat (genome BBAA), and in
      its two diploid progenitors Aegilops sharonensis (S(l)S(l)) and Triticum
      monococcum ssp. aegilopoides (A(m)A(m)). The expression of 60 out of 3072
      transcripts was reproducibly altered in the allotetraploid: 48 transcripts
      disappeared and 12 were activated. Transcript disappearance was caused by gene
      silencing or by gene loss. Gene silencing affected one or both homeologous loci
      and was associated in part with cytosine methylation. Gene loss or methylation
      had occurred already in the F(1) intergeneric hybrid or in the allotetraploid,
      depending on the locus. The silenced/lost genes included rRNA genes and genes
      involved in metabolism, disease resistance, and cell cycle regulation. The
      activated genes with a known function were all retroelements. These findings show
      that wide hybridization and chromosome doubling affect gene expression via
      genetic and epigenetic alterations immediately upon allopolyploid formation.
      These events contribute to the genetic diploidization of newly formed
      allopolyploids.

PMID- 11973317
TI  - Contrasting evolutionary forces in the Arabidopsis thaliana floral developmental
      pathway.
AB  - The floral developmental pathway in Arabidopsis thaliana is composed of several
      interacting regulatory genes, including the inflorescence architecture gene
      TERMINAL FLOWER1 (TFL1), the floral meristem identity genes LEAFY (LFY), APETALA1
      (AP1), and CAULIFLOWER (CAL), and the floral organ identity genes APETALA3 (AP3)
      and PISTILLATA (PI). Molecular population genetic analyses of these different
      genes indicate that the coding regions of AP3 and PI, as well as AP1 and CAL,
      share similar levels and patterns of nucleotide diversity. In contrast, the
      coding regions of TFL1 and LFY display a significant reduction in nucleotide
      variation, suggesting that these sequences have been subjected to a recent
      adaptive sweep. Moreover, the promoter of TFL1, unlike its coding region,
      displays high levels of diversity organized into two distinct haplogroups that
      appear to be maintained by selection. These results suggest that patterns of
      molecular evolution differ among regulatory genes in this developmental pathway,
      with the earlier acting genes exhibiting evidence of adaptive evolution.

PMID- 11973320
TI  - Improved confidence intervals in quantitative trait loci mapping by permutation
      bootstrapping.
AB  - The nonparametric bootstrap approach is known to be suitable for calculating
      central confidence intervals for the locations of quantitative trait loci (QTL).
      However, the distribution of the bootstrap QTL position estimates along the
      chromosome is peaked at the positions of the markers and is not tailed equally.
      This results in conservativeness and large width of the confidence intervals. In
      this study three modified methods are proposed to calculate nonparametric
      bootstrap confidence intervals for QTL locations, which compute noncentral
      confidence intervals (uncorrected method I), correct for the impact of the
      markers (weighted method I), or both (weighted method II). Noncentral confidence
      intervals were computed with an analog of the highest posterior density method.
      The correction for the markers is based on the distribution of QTL estimates
      along the chromosome when the QTL is not linked with any marker, and it can be
      obtained with a permutation approach. In a simulation study the three methods
      were compared with the original bootstrap method. The results showed that it is
      useful, first, to compute noncentral confidence intervals and, second, to correct
      the bootstrap distribution of the QTL estimates for the impact of the markers.
      The weighted method II, combining these two properties, produced the shortest and
      less biased confidence intervals in a large number of simulated configurations.

PMID- 11973319
TI  - Isolation and characterization of broad-spectrum disease-resistant Arabidopsis
      mutants.
AB  - To identify Arabidopsis mutants that constitutively express systemic acquired
      resistance (SAR), we constructed reporter lines expressing the firefly luciferase
      gene under the control of the SAR-inducible PR-1 promoter (PR-1/luc). After EMS
      mutagenesis of a well-characterized transgenic line, we screened 250,000 M(2)
      plants for constitutive expression of the reporter gene in vivo. From a mutant
      collection containing several hundred putative mutants, we concentrated on 16
      mutants lacking spontaneous hypersensitive response (HR) cell death. We mapped 4
      of these constitutive immunity (cim) mutants to chromosome arms. Constitutive
      expression of disease resistance was established by analyzing responses to
      virulent Peronospora parasitica and Pseudomonas syringae strains, by RNA blot
      analysis for endogenous marker genes, and by determination of salicylic acid
      levels in the mutants. The variety of the cim phenotypes allowed us to define
      distinct steps in both the canonical SAR signaling pathway and a separate pathway
      for resistance to Erysiphe cichoracearum, active in only a subset of the mutants.

PMID- 11973321
TI  - Mapping baroreceptor function to genome: a mathematical modeling approach.
AB  - To gain information about the genetic basis of a complex disease such as
      hypertension, blood pressure averages are often obtained and used as phenotypes
      in genetic mapping studies. In contrast, direct measurements of physiological
      regulatory mechanisms are not often obtained, due in large part to the time and
      expense required. As a result, little information about the genetic basis of
      physiological controlling mechanisms is available. Such information is important
      for disease diagnosis and treatment. In this article, we use a mathematical model
      of blood pressure to derive phenotypes related to the baroreceptor reflex, a
      short-term controller of blood pressure. The phenotypes are then used in a
      quantitative trait loci (QTL) mapping study to identify a potential genetic basis
      of this controller.

PMID- 11973322
TI  - Investigating the probability of sign inconsistency in the regression
      coefficients of markers flanking quantitative trait loci.
AB  - Estimates of the locations and effects of quantitative trait loci (QTL) can be
      obtained by regressing phenotype on marker genotype. Under certain basic
      conditions, the signs of regression coefficients flanking QTL must be the same.
      There is no guarantee, however, that the signs of the regression coefficient
      estimates will be the same. We use sign inconsistency to describe the situation
      in which there is disagreement between the signs of the estimated regression
      coefficients flanking QTL. The presence of sign inconsistency can undermine the
      effectiveness of QTL mapping strategies that presume intervals whose markers have
      regression coefficient estimates of differing sign to be devoid of QTL. This
      article investigates the likelihood of sign inconsistency under various
      conditions. We derive an analytic expression for the approximate probability of
      sign inconsistency in the single-QTL case. We also examine sign inconsistency
      probabilities when multiple QTL are present through simulation. We have
      discovered that the probability of sign inconsistency can be unacceptably high,
      even when the conditions for QTL detection are otherwise quite favorable.

PMID- 11973323
TI  - Homozygosity and linkage disequilibrium.
AB  - We illustrate how homozygosity of haplotypes can be used to measure the level of
      disequilibrium between two or more markers. An excess of either homozygosity or
      heterozygosity signals a departure from the gametic phase equilibrium: We
      describe the specific form of dependence that is associated with high (low)
      homozygosity and derive various linkage disequilibrium measures. They feature a
      clear biological interpretation, can be used to construct tests, and are
      standardized to allow comparison across loci and populations. They are
      particularly advantageous to measure linkage disequilibrium between highly
      polymorphic markers.

PMID- 11973324
TI  - Sperm competition and the dynamics of X chromosome drive: stability and
      extinction.
AB  - Several empirical studies of sperm competition in populations polymorphic for a
      driving X chromosome have revealed that Sex-ratio males (those carrying a driving
      X) are at a disadvantage relative to Standard males. Because the frequency of the
      driving X chromosome determines the population-level sex ratio and thus alters
      male and female mating rates, the evolutionary consequences of sperm competition
      for sex chromosome meiotic drive are subtle. As the SR allele increases in
      frequency, the ratio of females to males also increases, causing an increase in
      the male mating rate and a decrease in the female mating rate. While the former
      change may exacerbate the disadvantage of Sex-ratio males during sperm
      competition, the latter change decreases the incidence of sperm competition
      within the population. We analyze a model of the effects of sperm competition on
      a driving X chromosome and show that these opposing trends in male and female
      mating rates can result in two coexisting locally stable equilibria, one
      corresponding to a balanced polymorphism of the SR and ST alleles and the second
      to fixation of the ST allele. Stochastic fluctuations of either the population
      sex ratio or the SR frequency can then drive the population away from the
      balanced polymorphism and into the basin of attraction for the second
      equilibrium, resulting in fixation of the SR allele and extinction of the
      population.

PMID- 11973325
TI  - Considerations on study designs using the extreme sibpairs methods under
      multilocus oligogenic models.
AB  - Several issues pertinent to study designs employing extreme sibpairs (ESP)
      methods to detect complex oligogenic quantitative trait loci (QTL) are
      investigated in the setting of genome-wide multipoint scans. We demonstrate that
      when stringent alpha-levels are imposed (e.g., alpha = 0.00022 as recommended by
      Landers and Kruglyak), the power to detect a susceptibility locus could drop from
      83.6% under a one-locus model down to a hopeless 22.8% under a two-locus model of
      the same heritability h(2) = 0.5 and gene frequency (p = 0.1). We introduce the
      notion of joint power that is the power to detect linkage to at least one
      location over a given panel of markers across a genomic region and describe the
      effect of several design factors on such joint power in a multipoint scan.
      Moreover, power of analysis conditional on the IBD sharings of ESPs at a
      known/detected locus is examined and shown to increase substantively (to 93.3%
      under the previous two-locus model) in detecting novel trait loci. We conclude
      that with such remedies, the ESP design continues to be a relatively powerful
      design for mapping oligogenic QTL. However, when the effect of individual
      contributing loci becomes less tractable, especially when their contributions are
      "asymmetric," deliberation on balancing two types of statistical errors and a
      careful examination of possible contributions from multiple genetic factors
      and/or interaction effects are a must in designing an efficient study.

PMID- 11973326
TI  - The chromosome 1;11 translocation provides the best evidence supporting genetic
      etiology for schizophrenia and bipolar affective disorders.
AB  - Genetics is assumed to cause susceptibility to psychosis, but no major locus has
      been identified. These disorders cosegregate with a chromosome 1;11 translocation
      in a Scottish pedigree where 50% of the carriers are diseased. A genetic model
      originally proposed to explain the basis of these illnesses predicts such an
      outcome.

PMID- 11973327
TI  - Invasive filamentous growth of Candida albicans is promoted by Czf1p-dependent
      relief of Efg1p-mediated repression.
AB  - Filamentation of Candida albicans occurs in response to many environmental cues.
      During growth within matrix, Efg1p represses filamentation and Czf1p relieves
      this repression. We propose that Czf1p interacts with Efg1p, altering its
      function. The complex regulation of filamentation may reflect the versatility of
      C. albicans as a pathogen.

PMID- 11973329
TI  - Cleavage of Ig-Hepta at a "SEA" module and at a conserved G protein-coupled
      receptor proteolytic site.
AB  - Ig-Hepta is a member of a new subfamily of the heptahelical receptors and has an
      unusually long N terminus extending toward the extracellular side of the plasma
      membrane. Pulse-chase experiments in 293T cells using antisera specifically
      recognizing its N- and C-terminal regions demonstrated that Ig-Hepta is core
      glycosylated cotranslationally and proteolytically processed into a two-chain
      form in the endoplasmic reticulum, followed by maturation of oligosaccharide
      chains and dimerization. The cleavage occurs at two highly conserved sites: one
      in a "SEA" module (a module first identified in sperm protein, enterokinase, and
      agrin) near the N terminus and the other in the stalk region preceding the first
      transmembrane span, generating approximately 20-, 130-, and 32-kDa fragments. The
      latter two remain tightly associated non-covalently even after cleavage as
      revealed by immunoprecipitation of native and myc-tagged Ig-Hepta constructs that
      were transiently expressed in 293T cells. The dimer consisting of four chains,
      (130 kDa + 32 kDa)(2), is linked by disulfide bonds. A fusion protein of the
      extracellular domain of Ig-Hepta and the Fc domain of immunoglobulin was found to
      be a good substrate of the processing enzymes and used for determining the exact
      cleavage sites in the SEA module and juxtamembrane stalk region.

PMID- 11973328
TI  - EnvZ-OmpR interaction and osmoregulation in Escherichia coli.
AB  - EnvZ, a histidine kinase/phosphatase in Escherichia coli, responds to the
      osmolarity changes in the medium by regulating the phosphorylation state of the
      transcription factor OmpR, which controls the expression levels of outer membrane
      porin proteins OmpF and OmpC. Although both ompR and envZ genes are located on
      the ompB locus under the control of the ompB promoter and transcribed as a single
      polycistronic mRNA, the expression of envZ is known to be significantly less than
      ompR. However, to date no accurate estimation for the amounts of EnvZ and OmpR in
      the cell has been carried out. Here we examined the levels of EnvZ and OmpR in
      the wild-type strain MC4100 by quantitative Western blot analysis using anti-OmpR
      and anti-EnvZc (cytoplasmic domain of EnvZ) antisera. It was observed that during
      exponential growth in L-broth medium there were approximately 3500 and 100
      molecules per cell of OmpR and EnvZ, respectively. The levels of OmpR and EnvZ in
      MC4100 cells grown in a high osmolarity medium (nutrient broth with 20% sucrose)
      were about the same as those grown in L-broth, whereas they were 1.7-fold higher
      than those in a low osmolarity medium (nutrient broth). With His10-OmpR, we also
      determined that the K(d) value for the EnvZc-OmpR complex formation is 1.20 +/-
      0.17 microm. On the basis of these results, the molecular mechanism of
      osmoregulation of ompF and ompC is discussed.

PMID- 11973330
TI  - A "minimal" sodium channel construct consisting of ligated S5-P-S6 segments forms
      a toxin-activatable ionophore.
AB  - The large size (six membrane-spanning repeats in each of four domains) and
      asymmetric architecture of the voltage-dependent Na+ channel has hindered
      determination of its structure. With the goal of determining the minimum
      structure of the Na+ channel permeation pathway, we created two stable cell lines
      expressing the voltage-dependent rat skeletal muscle Na+ channel (micro1) with a
      polyhistidine tag on the C terminus (muHis) and pore-only micro1 (muPore)
      channels with S1-S4 in all domains removed. Both constructs were recognized by a
      Na+ channel-specific antibody on a Western blot. muHis channels exhibited the
      same functional properties as wild-type micro1. In contrast, muPore channels did
      not conduct Na+ currents nor did they bind [3H]saxitoxin. Veratridine caused 40
      and 54% cell death in muHis- and muPore-expressing cells, respectively. However,
      veratridine-induced cell death could only be blocked by tetrodotoxin in cells
      expressing muHis, but not muPore. Furthermore, using a fluorescent Na+ indicator,
      we measured changes in intracellular Na+ induced by veratridine and a brevotoxin
      analogue, pumiliotoxin. When calibrated to the maximum signal after addition of
      gramicidin, the maximal percent increases in fluorescence (deltaF) were 35 and
      31% in cells expressing muHis and muPore, respectively. Moreover, in the presence
      of 1 microm tetrodotoxin, deltaF decreased significantly to 10% in muHis- but not
      in muPore-expressing cells (43%). In conclusion, S5-P-S6 segments of micro1
      channels form a toxin-activable ionophore but do not reconstitute the Na+ channel
      permeation pathway with full fidelity.

PMID- 11973332
TI  - Trifluoroethanol increases the stability of Delta(5)-3-ketosteroid isomerase. 15N
      NMR relaxation studies.
AB  - In the equilibrium unfolding process of Delta(5)-3-ketosteroid isomerase from
      Pseudomonas testosteroni by urea, it was observed that the enzyme stability
      increases by 2.5 kcal/mol in the presence of 5% trifluoroethanol (TFE). To
      elucidate the increased enzyme stability by TFE, the backbone dynamics of
      Delta(5)-3-ketosteroid isomerase were studied in the presence and absence of 5%
      TFE by (15)N NMR relaxation measurements, and the motional parameters (S(2),
      tau(e), and R(ex)) were extracted from the relaxation data using the model-free
      formalism. The presence of 5% TFE causes little change or a slight increase in
      the order parameters (S(2)) for a number of residues, which are located mainly in
      the dimer interface region. However, the majority of the residues exhibit reduced
      order parameters in the presence of 5% TFE, indicating that high frequency (pico-
      to nanosecond) motions are generally enhanced by TFE. The results suggest that
      the entropy can be an important factor for the enzyme stability, and the increase
      in entropy by TFE is partially responsible for the increased stability of
      Delta(5)-3-ketosteroid isomerase.

PMID- 11973331
TI  - Expression of insulin-like growth factor-binding protein 5 in neuroblastoma cells
      is regulated at the transcriptional level by c-Myb and B-Myb via direct and
      indirect mechanisms.
AB  - Neuroblastoma (NB), a malignant childhood tumor deriving from the embryonic
      neural crest, is sensitive to the growth-stimulating effects of insulin-like
      growth factors (IGFs). Aggressive cases of this disease often acquire autocrine
      loops of IGF production, but the mechanisms through which the different
      components of the IGF axis are regulated in tumor cells remain unclear. Upon
      conditional expression of c-Myb in a NB cell line, we detected up-regulation of
      IGF1, IGF1 receptor, and insulin-like growth factor-binding protein 5 (IGFBP-5)
      expression. Analysis of the IGFBP-5 promoter revealed two potential Myb binding
      sites at position -59 to -54 (M1) and -429 to -424 (M2) from the transcription
      start site; both sites were bound by c-Myb and B-Myb in vitro and in vivo.
      Reporter assays carried out using the proximal region of the human IGFBP-5
      promoter demonstrated that c-Myb and B-Myb enhanced transcription. However, site
      directed mutagenesis and deletion of the Myb binding sites coupled with reporter
      assays revealed that M2 but not M1 was important for Myb-dependent
      transactivation of the IGFBP-5 promoter. The double mutant M1/M2 was still
      transactivated by c-Myb, suggesting the existence of Myb binding-independent
      mechanisms of IGFBP-5 promoter regulation. A constitutively active AKT
      transactivated the IGFBP-5 promoter, whereas the phosphatidylinositol 3-kinase
      inhibitor LY294002 suppressed it. Moreover, the kinase dead dominant negative
      K179M AKT mutant was able to inhibit transcription from the M2 and M1/M2 IGFBP-5
      mutant promoters. Deletion analysis of the IGFBP-5 promoter revealed that the AKT
      responsive region lies between nucleotides -334 and -83. Together, these data
      suggest that the Myb binding-independent transactivation of the IGFBP-5 promoter
      was due to the activation of the phosphatidylinositol 3-kinase/AKT pathway likely
      mediated by IGF1 receptor-dependent signals. Finally, IGFBP-5 was able to
      modulate proliferation of NB cells in a manner dependent on its concentration and
      on the presence of IGFs.

PMID- 11973333
TI  - Combinatorial interactions of p53, activating protein-2, and YB-1 with a single
      enhancer element regulate gelatinase A expression in neoplastic cells.
AB  - Gelatinase A, also denoted matrix metalloproteinase 2, plays multiple critical
      roles in the neoplastic process, including facilitation of neoangiogenesis and
      formation of distal metastases. The transcriptional regulation of the gelatinase
      A gene is under the control of strong, evolutionarily conserved cis-acting
      enhancer elements, designated the r2 (human) or RE-1 (rat), that harbor
      contiguous binding motifs for the transcription factors activating protein-2
      (AP2), p53, and YB-1. Using recombinant transcription factors, complex patterns
      of RE-1 binding were observed by electrophoretic mobility shift assay. Increased
      complex formation was detected with the AP2/YB-1 and AP2/p53 combinations, while
      YB-1 competed with p53 for binding. The combination of AP2, p53, and YB-1 yielded
      novel ternary complexes, particularly when binding to single-stranded RE-1
      probes. Transient transfection of hepatocellular carcinoma cell lines with a
      series of gelatinase A luciferase reporter constructs were in accordance with the
      binding patterns determined by electrophoretic mobility shift assay. Combined AP2
      and p53 increased gelatinase A luciferase reporter activity significantly, and
      the inclusion of YB-1 yielded further increase in both reporter activity and
      secreted levels of gelatinase A protein. YB-1 and p53 expression are increased
      following multiple genotoxic stresses, including irradiation, and the synergistic
      interactions of these induced transcription factors with the widely expressed AP2
      protein provide a probable pathophysiologic mechanism for the enhanced tumor cell
      synthesis of gelatinase A induced by radiation.

PMID- 11973334
TI  - Dominant and recessive compound heterozygous mutations in epidermolysis bullosa
      simplex demonstrate the role of the stutter region in keratin intermediate
      filament assembly.
AB  - Keratin intermediate filaments are important cytoskeletal structural proteins
      involved in maintaining cell shape and function. Mutations in the epidermal
      keratin genes, keratin 5 or keratin 14 lead to the disruption of keratin filament
      assembly, resulting in an autosomal dominant inherited blistering skin disease,
      epidermolysis bullosa simplex (EBS). We investigated a large EBS kindred who
      exhibited a markedly heterogeneous clinical presentation and detected two
      distinct keratin 5 mutations in the proband, the most severely affected. One
      missense mutation (E170K) in the highly conserved helix initiation peptide
      sequence of the 1A rod domain was found in all the affected family members. In
      contrast, the other missense mutation (E418K) was found only in the proband. The
      E418K mutation was located in the stutter region, an interruption in the heptad
      repeat regularity, whose function as yet remains unclear. We hypothesized that
      this mutated stutter allele was clinically silent when combined with the wild
      type allele but aggravates the clinical severity of EBS caused by the E170K
      mutation on the other allele. To confirm this in vitro, we transfected mutant
      keratin 5 cDNA into cultured cells. Although only 12.7% of the cells transfected
      with the E170K mutation alone showed disrupted keratin filament aggregations,
      significantly more cells (30.0%) cotransfected with both E170K and E418K
      mutations demonstrated keratin aggregation (p < 0.05). These transfection assay
      results corresponded to the heterogeneous clinical findings of the EBS patient in
      this kindred. We have identified the first case of both compound heterozygous
      dominant (E170K) and recessive (E418K) mutations in any keratin gene and
      confirmed the significant involvement of the stutter region in the assembly and
      organization of the keratin intermediate filament network in vitro.

PMID- 11973335
TI  - Acetylation of beta-catenin by CREB-binding protein (CBP).
AB  - Acetylation controls the activity of numerous proteins involved in regulating
      gene transcription as well as many other cellular processes. In this report we
      show that the CREB-binding protein (CBP) acetyltransferase acetylates beta
      catenin protein in vivo. beta-Catenin is a central component of the Wnt signaling
      pathway, which is of key importance in development as well as being heavily
      implicated in a variety of human cancers. We show that the CBP-mediated
      acetylation of beta-catenin occurs at a single site, lysine 49. Importantly, this
      lysine is frequently found mutated in cancer and is in a region of importance to
      the regulation of beta-catenin. We show that mutation of this site leads
      specifically to an increase in the ability of beta-catenin to activate the c-myc
      gene but not other beta-catenin-regulated genes. This suggests that acetylation
      of beta-catenin is involved in regulating Wnt signaling in a promoter-specific
      fashion.

PMID- 11973336
TI  - Recruitment of Gcn5-containing complexes during c-Myc-dependent gene activation.
      Structure and function aspects.
AB  - The N-terminal domain of c-Myc plays a key role in cellular transformation and is
      involved in both activation and repression of target genes as well as in
      modulated proteolysis of c-Myc via the proteasome. Given this functional
      complexity, it has been difficult to clarify the structures within the N terminus
      that contribute to these different processes as well as the mechanisms by which
      they function. We have used a simplified yeast model system to identify the
      primary determinants within the N terminus for (i) chromatin remodeling of a
      promoter, (ii) gene activation from a chromatin template in vivo, and (iii)
      interaction with highly purified Gcn5 complexes as well as other chromatin
      remodeling complexes in vitro. The results identify two regions that contain
      autonomous chromatin opening and gene activation activity, but both regions are
      required for efficient interaction with chromatin-remodeling complexes in vitro.
      The conserved Myc boxes do not play a direct role in gene activation, and Myc box
      II is not generally required for in vitro interactions with remodeling complexes.
      The yeast SAGA complex, which is orthologous to the human GCN5-TRRAP complex that
      interacts with Myc in human cells, plays a role in Myc-mediated chromatin opening
      at the promoter but may also be involved in later steps of gene activation.

PMID- 11973337
TI  - Factor VIIa induces tissue factor-dependent up-regulation of interleukin-8 in a
      human keratinocyte line.
AB  - Tissue factor (TF), a transmembrane receptor for the serine protease coagulation
      factor VII(a) (FVIIa), is the main initiator of the coagulation cascade. Through
      incompletely elucidated mechanisms, TF serves additional functions in tumor
      associated angiogenesis and metastasis. We have studied interleukin-8 (IL-8) as a
      possible link between TF-FVIIa complex formation and subsequent processes.
      Recombinant human FVIIa induced the up-regulation of both IL-8 mRNA and protein
      in a FVIIa dose- and time-dependent fashion. A neutralizing antibody to TF
      reduced this induction by 93 +/- 5%. Active site-inhibited FVIIa had no
      stimulatory effect and completely blocked that of FVIIa. This confirms that the
      increased IL-8 production was dependent on the formation of TF-FVIIa complexes
      and the proteolytic activity of FVIIa. The IL-8 promoter contains DNA binding
      sites for nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). In
      response to FVIIa, the DNA binding activity of both NF-kappaB and AP-1 was
      enhanced in an electrophoretic mobility shift assay. In addition, the IL-8
      promoter was transcriptionally activated both in a luciferase reporter system and
      a nuclear run-off assay. Moreover, IL-8 mRNA stability was significantly enhanced
      by FVIIa-induced activation of the mitogen-activated protein kinases ERK1/2 and
      p38. Taken together, TF-FVIIa signaling induced increased transcription as well
      as mRNA stabilization leading to the significant up-regulation of IL-8 protein
      synthesis.

PMID- 11973339
TI  - A selenoprotein in the plant kingdom. Mass spectrometry confirms that an opal
      codon (UGA) encodes selenocysteine in Chlamydomonas reinhardtii gluththione
      peroxidase.
AB  - Selenoproteins that contain the rare amino acid selenocysteine in their primary
      structure have been identified in diverse organisms such as viruses, bacteria,
      archea, and mammals, but so far not in yeast or plants. Among the most thoroughly
      investigated families of selenoenzymes are the animal glutathione peroxidases
      (GPXs). In the last few years, genes encoding GPX-like homologues from
      Chlamydomonas and higher plants have been isolated, but, unlike the animal ones,
      all of them have cysteine (rather than selenocysteine) residues in their
      catalytic site. In all organisms investigated that contain selenoproteins,
      selenocysteine is encoded by a UGA opal codon, which is usually a stop codon. We
      report here that, in Chlamydomonas reinhardtii, the cDNA-cloned sequence of a GPX
      homologue contains an internal TGA codon in frame to the ATG. Specific mRNA
      expression, protein production, and enzyme activity are selenium-dependent.
      Sequence analysis of the peptides produced by proteolytic digestion, performed by
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF MS), confirmed the presence of a selenocysteine residue at the
      predicted site and suggest its location in the mitochondria. Thus, our data
      present the first direct proof that a UGA opal codon is decoded in the plant
      kingdom to incorporate selenocysteine.

PMID- 11973342
TI  - Integral membrane protein biosynthesis: why topology is hard to predict.
AB  - Integral membrane protein biogenesis requires the coordination of several events:
      accurate targeting of the nascent chain to the membrane; recognition, orientation
      and integration of transmembrane (TM) domains; and proper formation of tertiary
      and quaternary structure. Initially unanticipated inter- and intra-protein
      interactions probably mediate each stage of biogenesis for single spanning,
      polytopic and C-terminally anchored membrane proteins. The importance of these
      regulated interactions is illustrated by analysis of topology prediction
      algorithm failures. Misassigned or misoriented TM domains occur because the
      primary sequence and overall hydrophobicity of a single TM domain are not the
      only determinants of membrane integration.

PMID- 11973338
TI  - The epithelial mitogen keratinocyte growth factor binds to collagens via the
      consensus sequence glycine-proline-hydroxyproline.
AB  - The binding of certain growth factors and cytokines to components of the
      extracellular matrix can regulate their local availability and modulate their
      biological activities. We show that mesenchymal cell-derived keratinocyte growth
      factor (KGF), a key stimulator of epithelial cell proliferation during wound
      healing, preferentially binds to collagens I, III, and VI. Binding is inhibited
      in a dose-dependent manner by denatured single collagen chains and collagen
      cyanogen bromide peptides. This interaction is saturable with dissociation
      constants of approximately 10(-8) to 10(-9) m and estimated molar ratios of up to
      three molecules of KGF bound to one molecule of triple helical collagen.
      Furthermore, collagen-bound KGF stimulated the proliferation of transformed
      keratinocyte or HaCaT cells. Ligand blotting of collagen-derived peptides points
      to a limited set of collagenous consensus sequences that bind KGF. By using
      synthetic collagen peptides, we defined the consensus sequence (Gly-Pro-Hyp)(n)
      as the collagen binding motif. We conclude that the preferential binding of KGF
      to the abundant collagens leads to a spatial pattern of bioavailable KGF that is
      dictated by the local organization of the collagenous extracellular matrix. The
      defined collagenous consensus peptide or its analogue may be useful in wound
      healing by increasing KGF bioactivity and thus modulating local epithelial
      remodeling and regeneration.

PMID- 11973343
TI  - Heat shock induces mini-Cajal bodies in the Xenopus germinal vesicle.
AB  - Cajal bodies are evolutionarily conserved nuclear organelles that are believed to
      play a central role in assembly of RNA transcription and processing complexes.
      Although knowledge of Cajal body composition and behavior has greatly expanded in
      recent years, little is known about the molecules and mechanisms that lead to the
      formation of these organelles in the nucleus. The Xenopus oocyte nucleus or
      germinal vesicle is an excellent model system for the study of Cajal bodies,
      because it is easy to manipulate and it contains 50-100 Cajal bodies with
      diameters up to 10 microm. In this study we show that numerous mini-Cajal bodies
      (less than 2 microm in diameter) form in the germinal vesicle after oocytes
      recover from heat shock. The mechanism for heat shock induction of mini-Cajal
      bodies is independent of U7 snRNA and does not require transcription or import of
      newly translated proteins from the cytoplasm. We suggest that Cajal bodies
      originate by self-organization of preformed components, preferentially on the
      surface of B-snurposomes.

PMID- 11973344
TI  - The molecular basis for the autoregulation of calponin by isoform-specific C
      terminal tail sequences.
AB  - The three genetic isoforms of calponin (CaP), h1, h2 and acidic, are
      distinguished mostly by their individual C-terminal tail sequences. Deletion of
      these sequences beyond the last homologous residue Cys273 increases actin
      filament association for all three isoforms, indicating a negative regulatory
      role for the unique tail regions. We have tested this hypothesis by constructing
      a series of deletion and substitution mutants for all three CaP isoforms. Here we
      demonstrate that the C-terminal sequences regulate actin association by altering
      the function of the second actin-binding site, ABS2, in CaP comprised of the
      three 29-residue calponin repeats. Removal of the inhibitory tail resulted in an
      increased binding and bundling activity, and caused a prominent re-localization
      of h2 CaP from the peripheral actin network to the central actin stress fibers in
      transfected A7r5 smooth muscle cells. Domain-swap experiments demonstrated that
      the tail sequence of h2 CaP can downregulate cytoskeletal association efficiently
      in all three CaP isoforms, whereas the tail of the smooth-muscle-specific h1 CaP
      variant had little effect. Site-directed mutagenesis further revealed that the
      negatively charged residues within the tail region are essential for this
      regulatory function. Finally we demonstrate that the tail sequences regulate the
      second actin-binding site (ABS2) and not the strong actin-binding ABS1 region in
      CaP.

PMID- 11973345
TI  - Integrin clustering induces kinectin accumulation.
AB  - Integrin receptors mediate the formation of adhesion complexes and play important
      roles in signal transduction from the extracellular matrix. Integrin-based
      adhesion complexes (IAC) contain proteins that link integrins to the cytoskeleton
      and recruit signaling molecules, including vinculin, paxillin, focal adhesion
      kinase, talin and alpha-actinin. In this study, we describe a approximately 160
      kDa protein that is markedly enriched at IAC induced by clustering integrins with
      fibronectin-coated beads. Protein sequence analysis reveals that this
      approximately 160 kDa protein is kinectin. Kinectin is an integral membrane
      protein found in endoplasmic reticulum, and it serves as a receptor for the motor
      protein kinesin. Fibronectin-induced IAC sequestered over half of the total
      cellular content of kinectin within 20 minutes. In addition, two other ER
      resident proteins, RAP [low-density lipoprotein receptor-related protein (LRP)
      receptor-associated protein] and calreticulin, were found to be clustered at IAC,
      whereas kinesin was not. Our results identify a novel class of constituents of
      IAC.

PMID- 11973346
TI  - Extracellular matrix histone H1 binds to perlecan, is present in regenerating
      skeletal muscle and stimulates myoblast proliferation.
AB  - Heparan sulfate chains of proteoglycans bind to and regulate the function of a
      wide variety of ligands. In myoblasts, heparan sulfate proteoglycans modulate
      basic fibroblast growth factor activity and regulate skeletal muscle
      differentiation. The aim of this study was to identify endogenous extracellular
      ligands for muscle cell heparan sulfate proteoglycans. [(35)S]heparin ligand blot
      assays identified a 33/30 kDa doublet (p33/30) in detergent/high ionic strength
      extracts and heparin soluble fractions obtained from intact C(2)C(12) myoblasts.
      p33/30 is localized on the plasma membrane or in the extracellular matrix where
      its level increases during muscle differentiation. Heparin-agarose-purified
      p33/30 was identified as histone H1. In vitro binding assays showed that histone
      H1 binds specifically to perlecan. Immunofluorescence microscopy showed that an
      extracellular pool of histone H1 colocalizes with perlecan in the extracellular
      matrix of myotube cultures and in regenerating skeletal muscle. Furthermore,
      histone H1 incorporated into the extracellular matrix strongly stimulated
      myoblast proliferation via a heparan-sulfate-dependent mechanism. These results
      indicate that histone H1 is present in the extracellular matrix of skeletal
      muscle cells, where it interacts specifically with perlecan and exerts a strong
      proliferative effect on myoblasts, suggesting a role for histone H1 during
      skeletal muscle regeneration.

PMID- 11973347
TI  - Sperm plasma-membrane-associated glutathione S-transferases as gamete recognition
      molecules.
AB  - Glutathione S-transferases (GSTs) are enzymes that detoxify electrophilic
      compounds. Earlier studies from our laboratory showed that anti-GST antibodies
      interfered with the fertilising ability of spermatozoa from Capra hircus (goat)
      in vitro, suggesting that GSTs are localised at the cell surface. In this study,
      we provide evidence for the presence of GSTs of 24 kDa on the sperm plasma
      membrane attached by non-covalent interactions. The GST activity associated with
      the spermatozoal plasma membrane was significantly higher than the activity
      present in the plasma membranes of brain cells, hepatocytes, spleenocytes and
      ventriculocytes. Analysis of GST isoforms demonstrates the presence of GST Pi and
      Mu on the sperm plasma membranes. Both isoforms were able to bind to solubilised
      as well as intact zona pellucida (ZP) through their N-terminal regions but failed
      to bind to ZP once the oocytes were fertilised. Solubilised goat ZP separates
      into three components, one of which, the ZP3-like component, bound to sperm GSTs.
      High concentrations of anti-GST antibodies or solubilised ZP led to aggregation
      of sperm GSTs, resulting in the release of acrosin. In contrast, inhibition of
      sperm GST binding to ZP, by saturation of binding sites for sperm GSTs on the
      solubilised ZP using peptides designed from the N-terminii of GST Pi or Mu or
      blocking of binding sites for ZP on sperm GSTs with antibodies raised against the
      N-terminal GST peptides, inhibited essential prefertilisation changes in sperm.
      These data therefore demonstrate the strategic location of catalytically active
      defensive enzymes on the sperm surface that also act as zona-binding proteins.
      Therefore, sperm-surface GSTs serve as bifunctional molecules in a
      transcriptionally inactive cell whose requirement for cellular defense and
      economy of molecules that it can carry is greater than that of any somatic cell
      type.

PMID- 11973348
TI  - Clik1: a novel kinase targeted to actin stress fibers by the CLP-36 PDZ-LIM
      protein.
AB  - In this report we have characterized a novel, ubiquitously expressed kinase,
      Clik1, that is predominantly nuclear and undergoes autophosphorylation. Yeast two
      hybrid analysis indicated a highly specific association between Clik1 and CLP-36,
      which was identified in 36 out of 37 Clik1-interacting clones. CLP-36 is a PDZ
      LIM protein that localizes to actin stress fibers in nonmuscle cells and
      associates with alpha-actinin via its PDZ-domain. The association of CLP-36 with
      Clik1, in turn, is mediated by the C-terminal part of CLP-36 containing the LIM
      domain, and association was not noted with the closely related ALP PDZ-LIM
      protein. Interestingly, the association with CLP-36 led to relocalization of the
      otherwise nuclear Clik1 kinase to actin stress fibers, where it disrupted the
      periodic staining pattern of CLP-36. Taken together these results establish the
      CLP-36 PDZ-LIM protein as an adapter, recruiting the Clik1 kinase to actin stress
      fibers in nonmuscle cells, and suggest that Clik1 represents a novel regulator of
      actin stress fibers.

PMID- 11973349
TI  - Endothelial cells genetically selected from differentiating mouse embryonic stem
      cells incorporate at sites of neovascularization in vivo.
AB  - Large scale purification of endothelial cells is of great interest as it could
      improve tissue transplantation, reperfusion of ischemic tissues and treatment of
      pathologies in which an endothelial cell dysfunction exists. In this study, we
      describe a novel genetic approach that selects for endothelial cells from
      differentiating embryonic stem (ES) cells. Our strategy is based on the
      establishment of ES-cell clones that carry an integrated puromycin resistance
      gene under the control of a vascular endothelium-specific promoter, tie-1. Using
      EGFP as a reporter gene, we first confirmed the endothelial specificity of the
      tie-1 promoter in the embryoid body model and in cells differentiated in 2D
      cultures. Subsequently, tie-1-EGFP ES cells were used as recipients for the tie-1
      driven puror transgene. The resulting stable clones were expanded and
      differentiated for seven days in the presence of VEGF before puromycin selection.
      As expected, puromycin-resistant cells were positive for EGFP and also expressed
      several endothelial markers, including CD31, CD34, VEGFR-1, VEGFR-2, Tie-1, VE
      cadherin and ICAM-2. Release from the puromycin selection resulted in the
      appearance of alpha-smooth muscle actin-positive cells. Such cells became more
      numerous when the population was cultured on laminin-1 or in the presence of TGF
      beta1, two known inducers of smooth muscle cell differentiation. The hypothesis
      that endothelial cells or their progenitors may differentiate towards a smooth
      muscle cell phenotype was further supported by the presence of cells expressing
      both CD31 and alpha-smooth muscle actin markers. Finally, we show that purified
      endothelial cells can incorporate into the neovasculature of transplanted tumors
      in nude mice. Taken together, these results suggest that application of
      endothelial lineage selection to differentiating ES cells may become a useful
      approach for future pro-angiogenic and endothelial cell replacement therapies.

PMID- 11973350
TI  - Cytoplasmic trafficking of IGF-II mRNA-binding protein by conserved KH domains.
AB  - The IGF-II mRNA-binding proteins (IMPs), which are composed of two RNA
      recognition motifs, (RRM) and four hnRNP K homology (KH) domains, have been
      implicated in subcytoplasmic localization of mRNAs during embryogenesis. The IMP
      family originated via two gene duplications before the divergence of vertebrates,
      and IMP homologues consisting of only the four KH motifs have been identified in
      Drosophila and Caenorhabditis elegans. Here we characterise the trafficking of
      GFP-IMP1 fusion proteins and determine the structural determinants for proper
      cytoplasmic localization. GFP-IMP1 is present in large 200-700 nm RNP granules,
      which are distributed along microtubules. In motile cells, GFP-IMP1 is
      transported towards the leading edge into the cortical region of the lamellipodia
      where it is connected to microfilaments. Granules travel in an ATP-dependent
      fashion at an average speed of 0.12 microm/s (range 0.04-0.22 microm/s), and
      cells switch from a delocalized to a localized pattern within 15-20 minutes. Both
      granule formation and localization are unaffected by removal of the two RRMs,
      whereas deletion of the KH domains, which mediate RNA-binding, impairs these
      functions. We conclude that IMP1 localization is associated with motility and
      that the major functions of IMP1 are carried out by the phylogenetically
      conserved KH domains.

PMID- 11973351
TI  - Embryonal subregion-derived stromal cell lines from novel temperature-sensitive
      SV40 T antigen transgenic mice support hematopoiesis.
AB  - Throughout life, the hematopoietic system requires a supportive microenvironment
      that allows for the maintenance and differentiation of hematopoietic stem cells
      (HSC). To understand the cellular interactions and molecules that provide these
      functions, investigators have previously established stromal cell lines from the
      late gestational stage and adult murine hematopoietic microenvironments. However,
      the stromal cell microenvironment that supports the emergence, expansion and
      maintenance of HSCs during mid-gestational stages has been largely unexplored.
      Since several tissues within the mouse embryo are known to harbor HSCs (i.e.
      aortagonads-mesonephros, yolk sac, liver), we generated numerous stromal cell
      clones from these mid-gestational sites. Owing to the limited cell numbers,
      isolations were performed with tissues from transgenic embryos containing the ts
      SV40 Tag gene (tsA58) under the transcriptional control of constitutive and
      ubiquitously expressing promoters. We report here that the growth and cloning
      efficiency of embryonic cells (with the exception of the aorta) is increased in
      the presence of the tsA58 transgene. Furthermore, our results show that the large
      panel of stromal clones isolated from the different embryonal subregions exhibit
      heterogeneity in their ability to promote murine and human hematopoietic
      differentiation. Despite our findings of heterogeneity in hematopoietic growth
      factor gene expression profiles, high-level expression of some factors may
      influence hematopoietic differentiation. Interestingly, a few of these stromal
      clones express a recently described chordin-like protein, which is an inhibitor
      of bone morphogenic proteins and is preferentially expressed in cells of the
      mesenchymal lineage.

PMID- 11973352
TI  - Cdk5 regulates cell-matrix and cell-cell adhesion in lens epithelial cells.
AB  - Cdk5 is a member of the cyclin-dependent kinase family, which is expressed
      predominantly in terminally differentiated neurons. Lower levels of Cdk5 are also
      found in a wide variety of cell types, including the lens. Although Cdk5 has been
      shown to play an important role in neuronal migration and neurite outgrowth, its
      function in non-neuronal cells is not known. Therefore, this study was undertaken
      to explore the role of Cdk5 in the lens. Results showed that, within the adult
      mouse lens, Cdk5 was localized to the cytoplasm, especially along the lateral
      membranes of differentiating primary fiber cells, which suggests a role in cell
      cell adhesion. Staining at the tips of elongating fiber cells was also
      particularly strong, suggesting a role in cell-matrix adhesion. To examine the
      possible role of Cdk5 in lens epithelial cell adhesion, we stably transfected
      N/N1003A rabbit lens epithelial cells with cDNAs for Cdk5 or a dominant-negative
      mutation, Cdk5-T33. Attachment to a fibronectin matrix, as measured with
      substrate-coated cell adhesion strips, was increased by Cdk5 overexpression,
      while an equivalent overexpression of Cdk5-T33 had no effect. Cdk5 also increased
      the rate of cell attachment and spreading as measured by electric cell-substrate
      impedance sensing (ECIS). In addition, Cdk5 overexpression decreased cell-cell
      adhesion as measured by a cell aggregation assay. These findings suggest that
      Cdk5 plays a role in regulating both cell-matrix and cell-cell interactions in
      the lens.

PMID- 11973353
TI  - Drac1 and Crumbs participate in amnioserosa morphogenesis during dorsal closure
      in Drosophila.
AB  - Dorsal closure of the Drosophila embryo involves morphological changes in two
      epithelia, the epidermis and the amnioserosa, and is a popular system for
      studying the regulation of epithelial morphogenesis. We previously implicated the
      small GTPase Drac1 in the assembly of an actomyosin contractile apparatus,
      contributing to cell shape change in the epidermis during dorsal closure. We now
      present evidence that Drac1 and Crumbs, a determinant of epithelial polarity, are
      involved in setting up an actomyosin contractile apparatus that drives
      amnioserosa morphogenesis by inducing apical cell constriction. Expression of
      constitutively active Drac1 causes excessive constriction of amnioserosa cells
      and contraction of the tissue, whereas expression of dominant-negative Drac1
      impairs amnioserosa morphogenesis. These Drac1 transgenes may be acting through
      their effects on the amnioserosa cytoskeleton, as constitutively active Drac1
      causes increased staining for F-actin and myosin, whereas dominant-negative Drac1
      reduces F-actin levels. Overexpression of Crumbs causes premature cell
      constriction in the amnioserosa, and dorsal closure defects are seen in embryos
      homozygous for hypomorphic crumbs alleles. The ability of constitutively active
      Drac1 to cause contraction of the amnioserosa is impaired in a crumbs mutant
      background. We propose that amnioserosa morphogenesis is a useful system for
      studying the regulation of epithelial morphogenesis by Drac1.

PMID- 11973354
TI  - Human cord blood-derived cells attain neuronal and glial features in vitro.
AB  - Neural stem cells are clonogenic, self-renewing cells with the potential to
      differentiate into brain-specific cell lines. Our study demonstrates that a
      neural-stem-cell-like subpopulation can be selected and expanded in vitro by the
      use of human umbilical cord blood cells, which are a relatively easily available
      starting material. Through a combination of antigen-driven magnetic cell sorting
      and subfractionation according to cell surface adhesive properties, we have
      isolated a clonogenic fraction devoid of hematopoietic or angiogenetic properties
      but with relatively high self-renewal potency. The resulting clones express
      nestin, a neurofilament protein that is one of the most specific markers of
      multipotent neural stem cells. In the presence of selected growth factors or in
      the rat brain co-culture system, the progeny of these cells can be oriented
      towards the three main neural phenotypes: neurons, astroglia and oligodendroglia.
      The cells show high commitment (about 30% and 40% of the population) to neuronal
      and astrocytic fate, respectively. Interestingly, upon differentiation, the
      neural-type precursor cells of cord blood origin also give rise to a relatively
      high proportion of oligodendrocytes - 11% of the total population of
      differentiating cells.

PMID- 11973355
TI  - The dynamics of plasma membrane PtdIns(4,5)P(2) at fertilization of mouse eggs.
AB  - A series of intracellular Ca2+ oscillations are responsible for triggering egg
      activation and cortical granule exocytosis at fertilization in mammals. These
      Ca2+ oscillations are generated by an increase in inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P(3)], which results from the hydrolysis of phosphatidylinositol 4,5
      bisphosphate [PtdIns(4,5)P(2)]. Using confocal imaging to simultaneously monitor
      Ca2+ and plasma membrane PtdIns(4,5)P(2) in single living mouse eggs we have
      sought to establish the relationship between the kinetics of PtdIns(4,5)P(2)
      metabolism and the Ca2+ oscillations at fertilization. We report that there is no
      detectable net loss of plasma membrane PtdIns(4,5)P(2) either during the latent
      period or during the subsequent Ca2+ oscillations. When phosphatidylinositol 4
      kinase is inhibited with micromolar wortmannin a limited decrease in plasma
      membrane PtdIns(4,5)P(2) is detected in half the eggs studied. Although we were
      unable to detect a widespread loss of PtdIns(4,5)P(2), we found that
      fertilization triggers a net increase in plasma membrane PtdIns(4,5)P(2) that is
      localized to the vegetal cortex. The fertilization-induced increase in
      PtdIns(4,5)P(2) follows the increase in Ca2+, is blocked by Ca2+ buffers and can
      be mimicked, albeit with slower kinetics, by photoreleasing Ins(1,4,5)P(3).
      Inhibition of Ca2+-dependent exocytosis of cortical granules, without interfering
      with Ca2+ transients, inhibits the PtdIns(4,5)P(2) increase. The increase appears
      to be due to de novo synthesis since it is inhibited by micromolar wortmannin.
      Finally, there is no increase in PtdIns(4,5)P(2) in immature oocytes that are not
      competent to extrude cortical granules. These studies suggest that fertilization
      does not deplete plasma membrane PtdIns(4,5)P(2) and that one of the pathways for
      increasing PtdIns(4,5)P(2) at fertilization is invoked by exocytosis of cortical
      granules.

PMID- 11973357
TI  - Regulation, mechanisms and proposed function of ferritin translocation to cell
      nuclei.
AB  - Ferritin is traditionally considered a cytoplasmic iron-storage protein, but
      recent reports indicate that it is also found in cell nuclei. Nuclear ferritin
      has been proposed to be involved in both the protection of DNA and the
      exacerbation of iron-induced oxidative damage to DNA. We demonstrate that H-rich
      ferritin is present in the nucleus of human astrocytoma tumor cells. To study the
      mechanism and regulation of ferritin translocation to the nucleus, we developed a
      cell culture model using SW1088 human astrocytoma cells. Changes in cellular iron
      levels, cytokine treatments and hydrogen peroxide exposure affected the
      distribution of ferritin between the cytosol and the nucleus. Ferritin enters the
      nucleus via active transport through the nuclear pore and does not require NLS
      bearing cytosolic factors for transport. Furthermore, H-rich ferritin is
      preferred over L-rich ferritin for uptake into the nucleus. Whole cell
      crosslinking studies revealed that ferritin is associated with DNA. Ferritin
      protected DNA from iron-induced oxidative damage in both in vitro and in cell
      culture models. These results strongly suggest a novel role for ferritin in
      nuclear protection. This work should lead to novel characterization of ferritin
      functions in the context of genomic stability and may have unparalleled
      biological significance in terms of the accessibility of metals to DNA. The
      knowledge generated as a result of these studies will also improve our
      understanding of iron-induced damage of nuclear constituents.

PMID- 11973356
TI  - Sequential activation of individual PKC isozymes in integrin-mediated muscle cell
      spreading: a role for MARCKS in an integrin signaling pathway.
AB  - To understand how muscle cell spreading and survival are mediated by integrins,
      we studied the signaling events initiated by the attachment of muscle cells to
      fibronectin (FN). We have previously demonstrated that muscle cell spreading on
      FN is mediated by alpha5beta1 integrin, is associated with rapid phosphorylation
      of focal adhesion kinase and is dependent on activation of protein kinase C
      (PKC). Here we investigated the role of individual PKC isozymes in these cellular
      processes. We show that alpha, delta and epsilonPKC are expressed in muscle cells
      and are activated upon integrin engagement with different kinetics - epsilonPKC
      was activated early, whereas alpha and deltaPKC were activated later. Using
      isozyme-specific inhibitors, we found that the activation of epsilonPKC was
      necessary for cell attachment to FN. However, using isozyme-specific activators,
      we found that activation of each of three isozymes was sufficient to promote the
      spreading of alpha5-integrin-deficient cells on FN. To investigate further the
      mechanism by which integrin signaling and PKC activation mediate cell spreading,
      we studied the effects of these processes on MARCKS, a substrate of PKC and a
      protein known to regulate actin dynamics. We found that MARCKS was localized to
      focal adhesion sites soon after cell adhesion and that MARCKS translocated from
      the membrane to the cytosol during the process of cell spreading. This
      translocation correlated with different phases of PKC activation and with
      reorganization of the actin cytoskeleton. Using MARCKS-antisense cDNA, we show
      that alpha5-expressing cells in which MARCKS expression is inhibited fail to
      spread on FN, providing evidence for the crucial role of MARCKS in muscle cell
      spreading. Together, the data suggest a model in which early activation of
      epsilonPKC is necessary for cell attachment; the later activation of alpha or
      deltaPKC may be necessary for the progression from attachment to spreading. The
      mechanism of PKC-mediated cell spreading may be via the phosphorylation of
      signaling proteins, such as MARCKS, that are involved in the reorganization of
      the actin cytoskeleton.

PMID- 11973358
TI  - Activation, processing and trafficking of extracellular heparanase by primary
      human fibroblasts.
AB  - Heparanase is a heparan-sulfate-degrading endoglycosidase that has important
      roles in various biological processes, including angiogenesis, wound healing and
      metastatsis. Human heparanase is synthesized as a 65 kDa latent precursor, which
      is proteolytically processed into a highly active 50 kDa form. Extracellular
      heparanase is found in various tissues and is utilized by both normal cells and
      metastatic cancer cells to degrade heparan sulfate moieties in basement membranes
      and extracellular matrices. This study characterizes the processing and
      trafficking events associated with cellular activation of extracellular
      heparanase. We show that primary human fibroblasts are capable of binding and
      converting the 65 kDa heparanase precursor into its highly active 50 kDa form,
      concomitantly with its cytoplasmic accumulation. Heparanase uptake depends on the
      actin cytoskeleton integrity, resulting in a prolonged storage of the enzyme,
      mainly in endosomal structures. Heparanase endocytosis and its proteolytic
      activation are independent processes, indicating that heparanase cleavage is a
      cell surface event. Heparin completely inhibits heparanase endocytosis but only
      partially inhibits its association with the cells, suggesting that cell surface
      heparan sulfate moieties play a specific role in its endocytosis. Cellular
      binding and uptake of extracellular heparanase control its activation, clearance
      rate and storage within the cells.

PMID- 11973359
TI  - Resistance of keratinocytes to TGFbeta-mediated growth restriction and apoptosis
      induction accelerates re-epithelialization in skin wounds.
AB  - The pleiotropic growth factor TGFbeta plays an important role in regulating
      responses to skin injury. TGFbeta targets many different cell types and is
      involved in all aspects of wound healing entailing inflammation, re
      epithelialization, matrix formation and remodeling. To elucidate the role of
      TGFbeta signal transduction in keratinocytes during cutaneous wound healing, we
      have used transgenic mice expressing a dominant negative type II TGFbeta receptor
      exclusively in keratinocytes. We could demonstrate that this loss of TGFbeta
      signaling in keratinocytes led to an accelerated re-epithelialization of full
      thickness excisional wounds accompanied by an increased proliferation in
      keratinocytes at the wound edge. Furthermore, we show that impaired TGFbeta
      signaling in keratinocytes reduces apoptosis in re-epithelialized wounds of
      transgenic animals. A cDNA array identified the transcription factor early growth
      response factor 1 (Egr1) as a target gene for TGFbeta in late phases of the wound
      healing process. As a member of the immediate-early gene family, Egr1 is
      upregulated shortly after injury and induces the expression of growth factor
      genes. We could demonstrate that Egr1 expression is also upregulated in skin
      wounds which have already undergone re-epithelialization. In conclusion, we
      attribute the enhanced re-epithelialization in our transgenics to the resistance
      of keratinocytes to TGFbeta-mediated growth restriction and apoptosis induction.
      We also propose a new role for TGFbeta induced Egr1 in late phase wound repair.

PMID- 11973360
TI  - Differential regulation of Rho GTPases by beta1 and beta3 integrins: the role of
      an extracellular domain of integrin in intracellular signaling.
AB  - Integrins mediate cell adhesion and signal transduction at focal adhesions. Here
      we investigate the roles of integrin beta subunits in the regulation of actin
      cytoskeletal structure and the activities of Rho and Rac. The overexpression of
      beta3 integrin in Chinese hamster ovary cells enhances Rho activity and stress
      fiber formation, whereas the overexpression of beta1 integrin increases Rac
      activity and lamellipodia formation. The overexpression of a mutant beta1-3-1
      integrin, in which the extracellular I-domain-like sequence of beta1 integrin has
      been replaced with the corresponding sequence of beta3 integrin, also enhances
      Rho activity and the formation of stress fibers. Our results demonstrate that
      beta1 and beta3 integrins differentially regulate the activities of Rho family
      GTPases and that the extracellular domains of integrin beta subunits play a
      critical role in transducing the extracellular ligand-binding information into
      specific intracellular signaling events.

PMID- 11973361
TI  - Agonist-induced phasic and tonic responses in smooth muscle are mediated by
      InsP(3).
AB  - Many cellular functions are regulated by agonist-induced InsP(3)-evoked Ca2+
      release from the internal store. In non-excitable cells, predominantly, the
      initial Ca2+ release from the store by InsP(3) is followed by a more sustained
      elevation in [Ca2+](i) via store-operated Ca2+ channels as a consequence of
      depletion of the store. Here, in smooth muscle, we report that the initial
      transient increase in Ca2+, from the internal store, is followed by a sustained
      response also as a consequence of depletion of the store (by InsP(3)), but,
      influx occurs via voltage-dependent Ca2+ channels. Contractions were measured in
      pieces of whole distal colon and membrane currents and [Ca2+](i) in single
      colonic myocytes. Carbachol evoked phasic and tonic contractions; only the latter
      were abolished in Ca2+-free solution. The tonic component was blocked by the
      voltage-dependent Ca2+ channel blocker nimodipine but not by the store-operated
      channel blocker SKF 96365. InsP(3) receptor inhibition, with 2-APB, attenuated
      both the phasic and tonic components. InsP(3) may regulate tonic contractions via
      sarcolemma Ca2+ entry. In single cells, depolarisation (to approximately -20 mV)
      elevated [Ca2+](i) and activated spontaneous transient outward currents (STOCs).
      CCh suppressed STOCs, as did caffeine and InsP(3). InsP(3) receptor blockade by 2
      APB or heparin prevented CCh suppression of STOCs; protein kinase inhibition by H
      7 or PKC(19-36) did not. InsP(3) suppressed STOCs by depleting a Ca2+ store
      accessed separately by the ryanodine receptor (RyR). Thus depletion of the store
      by RyR activators abolished the InsP(3)-evoked Ca2+ transient. RyR inhibition (by
      tetracaine) reduced only STOCs but not the InsP(3) transient. InsP(3) contributes
      to both phasic and tonic contractions. In the former, muscarinic receptor-evoked
      InsP(3) releases Ca2+ from an internal store accessed by both InsP(3) and RyR.
      Depletion of this store by InsP(3) alone suppresses STOCs, depolarises the
      sarcolemma and permits entry of Ca2+ to generate the tonic component. Therefore,
      by lowering the internal store Ca2+ content, InsP(3) may generate a sustained
      smooth muscle contraction. These results provide a mechanism to account for
      phasic and tonic smooth muscle contraction following receptor activation.

PMID- 11973362
TI  - New perspectives in PDGF receptor downregulation: the main role of
      phosphotyrosine phosphatases.
AB  - Uncontrolled activation of receptor tyrosine kinases (RTKs) is implicated in the
      proliferation of cancerous cells, and deficiencies in RTKs results in
      pathological conditions such as developmental abnormalities and
      immunodeficiencies. Tight regulation of RTK cascades is therefore critical for
      eliciting an appropriate type and level of response to external stimuli. The aim
      of this work is to compare different RTK downregulation mechanisms, such as
      ligandinduced internalisation, ubiquitin-mediated proteolysis and
      dephosphorylation by protein phosphotyrosine phosphatase (PTPs). We choose
      platelet-derived growth factor receptor (PDGF-r) in NIH3T3 cells as a model of
      RTK. Our data suggest that PDGF-r internalisation could be mainly considered as a
      positive signaling system, as it is involved in MAPK activation rather than a
      downregulation of the mitotic signal. Inhibition of receptor ubiquitination does
      not result in regulation of PDGF-r tyrosine phosphorylation and does not lead to
      variation of intracellular signalling pathways. The overall PDGF-r protein
      degradation upon PDGF stimulation does not exceed 30-40% of the total receptor;
      thus the receptor remains functionally active for further stimulation. On the
      contrary, PTP-dependent dephosphorylation of the activated receptors appears to
      play a crucial role. In fact, inhibition of PTP upon PDGF stimulation results in
      upregulation of receptor phosphorylation level, of PI3K recruitment and
      activation and of cell cycle rate. On the contrary, PTP-dependent
      dephosphorylation does not affect the endosomic pool of activated receptor.
      Furthermore, we demonstrate that PDGF-r downregulation by means of PTP
      dephosphorylation is important for both short term (2 hours) and long-lasting (up
      to 8 hours) PDGF-r activation. Herein we propose a revisited model of PDGF-r
      downregulation in which PTPs dephosphorylation retains a major role, conferring
      on receptor internalisation a signal transduction function.

PMID- 11973363
TI  - PLC-gamma1 is required for IGF-I protection from cell death induced by loss of
      extracellular matrix adhesion.
AB  - Phospholipase C-gamma1, a tyrosine kinase substrate, hydrolyses
      phosphatidylinositol 4,5-bisphosphate to produce inositol 1,4,5-trisphosphate and
      diacylglycerol, which act as second messenger moleculesto mobilize intracellular
      calcium and activate protein kinase C, respectively. We have investigated the
      role of phospholipase C-gamma1 in anoikis, or cell death, induced by the loss of
      extracellular matrix adhesion. Spontaneously immortalized mouse embryonic
      fibroblasts nullizygous at the Plcg1 locus (Plcg1(-/-)), referred to as Null
      cells, were derived from targeted gene disruption experiments. Subsequently,
      phospholipase C-gamma1 was re-expressed in these cells to derive Null+ cells. The
      Null and Null+ cells were then placed in suspension to induce cell death, which
      was measured directly as well as by the induction of caspase 3, as an index of
      programmed cell death or apoptosis. The results demonstrate that insulin-like
      growth factor can rescue Null+ cells but not Null cells from suspension-induced
      cell death. This demonstrates that phospholipase C-gamma1 is required for insulin
      like growth factor dependent cell survival under these conditions. Lastly, the
      data demonstrate that insulinlike growth factor stimulated tyrosine
      phosphorylation of phospholipase C-gamma1 in both adherent and suspension cells.

PMID- 11973364
TI  - Genetic and morphological evidence for two parallel pathways of cell-cycle
      coupled cytokinesis in Dictyostelium.
AB  - Myosin-II-null cells of Dictyostelium discoideum cannot divide in suspension,
      consistent with the dogma that myosin II drives constriction of the cleavage
      furrow and, consequently, cytokinesis (cytokinesis A). Nonetheless, when grown on
      substrates, these cells exhibit efficient, cell-cycle-coupled division,
      suggesting that they possess a novel, myosin-II-independent, adhesion-dependent
      method of cytokinesis (cytokinesis B). Here we show that double mutants lacking
      myosin II and either AmiA or coronin, both of which are implicated in cytokinesis
      B, are incapable of cell-cycle-coupled cytokinesis. These double mutants
      multiplied mainly by cytokinesis C, a third, inefficient, method of cell
      division, which requires substrate adhesion and is independent of cell cycle
      progression. In contrast, double mutants lacking AmiA and coronin were no sicker
      than each of the single mutants, indicating that the severe defects of myosin II(
      )/AmiA(-) or myosin II(-)/coronin(-) mutants are not simple additive effects of
      two mutations. We take this as genetic evidence for two parallel pathways both of
      which lead to cell-cycle-coupled cytokinesis. This conclusion is supported by
      differences in morphological changes during cytokinesis in the mutant cell lines.

PMID- 11973365
TI  - Pulmonary dead-space fraction as a risk factor for death in the acute respiratory
      distress syndrome.
AB  - BACKGROUND: No single pulmonary-specific variable, including the severity of
      hypoxemia, has been found to predict the risk of death independently when
      measured early in the course of the acute respiratory distress syndrome. Because
      an increase in the pulmonary dead-space fraction has been described in
      observational studies of the syndrome, we systematically measured the dead-space
      fraction early in the course of the illness and evaluated its potential
      association with the risk of death. METHODS: The dead-space fraction was
      prospectively measured in 179 intubated patients, a mean (+/-SD) of 10.9+/-7.4
      hours after the acute respiratory distress syndrome had developed. Additional
      clinical and physiological variables were analyzed with the use of multiple
      logistic regression. The study outcome was mortality before hospital discharge.
      RESULTS: The mean dead-space fraction was markedly elevated (0.58+/-0.09) early
      in the course of the acute respiratory distress syndrome and was higher among
      patients who died than among those who survived (0.63+/-0.10 vs. 0.54+/-0.09,
      P<0.001). The dead-space fraction was an independent risk factor for death: for
      every 0.05 increase, the odds of death increased by 45 percent (odds ratio, 1.45;
      95 percent confidence interval, 1.15 to 1.83; P=0.002). The only other
      independent predictors of an increased risk of death were the Simplified Acute
      Physiology Score II, an indicator of the severity of illness (odds ratio, 1.06;
      95 percent confidence interval, 1.03 to 1.08; P<0.001) and quasistatic
      respiratory compliance (odds ratio, 1.06; 95 percent confidence interval, 1.01 to
      1.10; P=0.01). CONCLUSIONS: Increased dead-space fraction is a feature of the
      early phase of the acute respiratory distress syndrome. Elevated values are
      associated with an increased risk of death.

PMID- 11973366
TI  - Assessments of medical care by enrollees in for-profit and nonprofit health
      maintenance organizations.
AB  - BACKGROUND: It is uncertain how assessments of medical care differ between
      enrollees in for-profit and nonprofit health maintenance organizations (HMOs).
      METHODS: We analyzed the relation between the profit status of HMOs and
      enrollees' assessments of their care. We used data from two national surveys from
      the Community Tracking Study: the Household Survey, 1996-1997, and the 1997-1998
      Insurance Followback Survey. The final sample included 13,271 persons under 65
      years of age (10,654 adults and 2617 children) with employer-sponsored insurance
      who obtained health care through an HMO. A total of 12,445 enrollees who reported
      their health status as excellent, very good, or good were considered to be
      healthy; 826 with self-reported fair or poor health were considered to be sick.
      RESULTS: In the sample as a whole, enrollees in nonprofit plans were more likely
      to be very satisfied with their overall care than enrollees in for-profit plans
      (adjusted means, 64.0 percent and 58.1 percent, respectively; P=0.01). Among
      enrollees in for-profit HMOs, sick enrollees were more likely than healthy
      enrollees to report unmet need or delayed care (17.4 percent vs. 13.1 percent,
      P=0.004) and organizational or administrative barriers to care (12.9 percent vs.
      9.0 percent, P<0.001); they also reported higher out-of-pocket spending during
      the previous year ($731 vs. $480, P=0.002). For nonprofit HMOs, there was only
      one significant difference between the ratings of healthy and sick enrollees;
      sick enrollees expressed more trust in doctors to refer when needed. CONCLUSIONS:
      Although there are few overall differences in assessments of medical care between
      enrollees in for-profit and nonprofit HMOs, for-profit HMOs are rated less
      favorably than nonprofit HMOs by patients who have self-reported fair or poor
      health.

PMID- 11973367
TI  - Clinical practice. Peanut allergy.

PMID- 11973368
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 13-2002. A 43-year-old man with renal carcinoma and worsening
      dyspnea.

PMID- 11973369
TI  - The nuts and bolts of peanut allergy.

PMID- 11973370
TI  - Clinical investigation of smallpox in 1767.

PMID- 11973371
TI  - Naltrexone for alcohol dependence.

PMID- 11973372
TI  - Patent foramen ovale, atrial septal aneurysm, and recurrent stroke.

PMID- 11973373
TI  - The hemolytic-uremic syndrome.

PMID- 11973374
TI  - Post-traumatic stress disorder and sleep.

PMID- 11973375
TI  - Mild asthma.

PMID- 11973376
TI  - Potential hazard of wound licking.

PMID- 11973377
TI  - Bioterrorism, public health, and civil liberties.

PMID- 11973378
TI  - Thygeson lecture. Amniotic membrane transplantation: why is it effective?
AB  - PURPOSE: To review the uses and previously proposed mechanisms of action of
      amniotic membrane transplantation (AMT) and to suggest a new mechanism of action
      for the effectiveness of AMT in resolving a persistent epithelial defect (PED).
      METHODS: Significant clinical and experimental publications are reviewed.
      RESULTS: Evidence from the scientific literature suggests a new hypothesis for
      the effectiveness of AMT in the reepithelialization of a PED and the reduction of
      corneal stromal inflammation and continued fibrosis. CONCLUSION: It is suggested
      that reepithelialization of a PED, and hence the reduction of stromal
      inflammation and continued fibrosis following reepithelialization, is aided by
      the combination of oxygenation, moisture and protection of the fragile epithelium
      by the amniotic membrane.

PMID- 11973379
TI  - Symptomatic management of postoperative bullous keratopathy with nonpreserved
      human amniotic membrane.
AB  - PURPOSE: To report the results of the management of painfully symptomatic
      postoperative bullous keratopathy (PBK) by performing a nonpreserved human
      amniotic membrane (NP-AMT) transplantation in nine eyes with poor visual
      potential. METHODS: A prospective, comparative, nonrandomized management of
      symptomatic PBK was done by performing a complete corneal de-epithelialization
      followed by a NP-AMT transplantation (NP-AMT group) or no NP-AMT transplantation
      (control group). We evaluated time for re-epithelialization, patient's symptoms,
      and appearance of new bullae. RESULTS: In the NP-AMT group, mean follow-up time
      was 40 weeks. Mean re-epithelialization time was 11.2 days. Symptoms of PBK
      resolved completely in eight patients (88%), who were asymptomatic and showing
      very quiet eyes from postoperative day 1, and resolved partially in one patient
      in whom we observed barely symptomatic bullae at the peripheral NP-AMT border
      (sixth postoperative week) and an asymptomatic one at the corneal center under
      the NP-AMT (seventh postoperative week). In the control group, mean follow-up
      time was 18 weeks; there were recurrences of symptomatic bullae in four of five
      patients at a mean time of 6.3 days. CONCLUSIONS: NP-AMT is a good alternative
      for the management of painful PBK in eyes with poor visual potential; NP-AMT is
      widely available, the technique is easy to perform, and it has good results from
      both the symptomatic and esthetic standpoint.

PMID- 11973380
TI  - Ocular microfluctuations and videokeratoscopy.
AB  - PURPOSE: We aimed to minimize the effect of ocular microfluctuations during
      videokeratoscopy to improve the qualitative and quantitative analysis of corneal
      topography. METHODS: A technique was developed to measure the tilt, displacement,
      and cyclotorsion in multiple videokeratographs from the same cornea. This
      information was used to reposition each videokeratograph according to the average
      position of a sample of multiple measurements. The corneal topography of 10
      subjects was measured 20 times each, using videokeratoscopy. RESULTS: The root
      mean square error calculated from difference between single videokeratographs and
      the average videokeratograph decreased by an average of 24.6% for the 10
      subjects' data. The standard deviation of some terms of Zernike polynomials
      fitted to the cornea was significantly reduced after the procedure. CONCLUSION:
      The method that we propose can improve the precision performance of
      videokeratoscopy in multiple measurements of corneal topography.

PMID- 11973381
TI  - Tolerability and safety of two new preservative-free tear film substitutes.
AB  - PURPOSE: The tolerability, safety, and visual comfort of two new tear film
      substitutes were studied in a phase I clinical study. METHODS: Two amphipathic
      lipids (phosphatidylcholine, cholesterol, sphingomyelin, and gangliosides)
      containing solutions (I and II) of well-defined stoichiometry, free of
      preservatives, were studied in 20 eyes of 20 healthy volunteers (age range, 26-32
      years) in a randomized, double-blind, crossover study. Randomization was achieved
      by treating one eye of each volunteer four times daily for 7 days with composite
      solution I. The contralateral eye served as a control. After a washout interval
      of 7 days, the same eye was treated similarly four times daily with the solution
      II under randomizing conditions. Slit-lamp biomicroscopy, visual acuity, visual
      analog scales, and side effects were monitored at the beginning of the study
      weekly and for 3 weeks. RESULTS: The tear substitutes proved to have no influence
      on the visual acuity and were safe and well tolerated. No allergic reactions or
      any other side effects such as hyperemia, corneal disturbance, and foreign body
      deposits were observed in any volunteer. CONCLUSION: The biophysical properties
      of the amphipathic lipids comprising the two preservative-free tear film
      substitutes were studied in monolayer experiments. They form reversibly
      compressible and expandable monomolecular films at the air-water interface, a
      prerequisite for the mimicry of the tear film produced normally by meibomian
      glands. The efficacy and safety of both medications will be investigated in
      patients with keratoconjunctivitis sicca and dry eye syndrome in future
      experiments.

PMID- 11973382
TI  - Cogan syndrome.
AB  - PURPOSE: To lead ophthalmologists to consider Cogan syndrome when managing a
      patient presenting with keratitis or other ocular inflammation accompanied by
      sensorineural hearing loss. METHODS: Seven patients affected by Cogan syndrome
      were studied: two males and five females, ranging from 27 to 65 years of age
      (mean age: 41 years). Subjects were evaluated for a period ranging from 22 to 46
      months (mean follow up time: 29.2 months). All patients were treated with
      immunosuppressive drug combination therapy (IDCT). RESULTS: Three patients were
      affected by classic Cogan syndrome (i.e., vestibuloauditory symptoms and later
      sensorineural hearing loss and interstitial keratitis). Four patients presented
      atypical Cogan syndrome (i.e., sensorineural hearing loss and chronic ocular
      inflammation such as uveitis, scleritis, conjunctivitis, retinal vasculitis,
      etc.). Four of these patients had a late diagnosis. Two of them were diagnosed
      when they already had a cochlear implant, one with bilateral deafness underwent
      cochlear implantation 1 year after the beginning of IDCT, one had severe
      bilateral hearing loss that improved during the first year of IDCT, and then
      rapidly worsened to total deafness in 1 month following an episode of severe
      systemic hypotension. Three patients who had an early diagnosis of Cogan syndrome
      had no worsening of vestibuloauditory dysfunction during the follow up period.
      CONCLUSION: Diagnosis of Cogan syndrome should not be overlooked by
      ophthalmologists in all patients with recurrent ocular inflammatory disease
      associated with vestibuloauditory symptoms. Early diagnosis is essential to
      commence the appropriate immunosuppressive therapy that may prevent permanent
      hearing loss and ocular dysfunction.

PMID- 11973383
TI  - Corneal endothelial cell morphology in patients undergoing cataract surgery.
AB  - PURPOSE: To evaluate the effect of age, gender, axial length, and presence of
      type II diabetes on corneal endothelial cell morphology in patients undergoing
      cataract surgery. METHODS: The corneal endothelial cell morphology was
      investigated in 1,819 eyes of 1,394 patients before cataract surgery. The
      parameters examined include cell density, coefficient of variation of cell area,
      and percentage of hexagonal cells. The effects of age, gender, axial length, and
      presence of type II diabetes on these parameters were evaluated. RESULTS: The
      mean values in endothelial cell density, coefficient of variation of cell area,
      and percentage of hexagonal cells in all eyes, were 2,543 +/- 254 cells/mm2
      (range, 1906-3,252), 0.64 +/- 0.10 (range, 0.34-1.00), and 37.9 +/- 7.1% (range,
      17.6-61.7), respectively. Stepwise multiple regression analysis revealed that age
      was the only explanatory variable to be relevant to corneal endothelial cell
      density (R = -0.201, p < 0.0001), coefficient of variation of cell area (R =
      0.066, p = 0.0046), and percentage of hexagonal cells (R = -0.086, p = 0.0002).
      The other variables, including gender, axial length, and presence of type II
      diabetes mellitus, were found to be irrelevant to any of the parameters of
      corneal endothelial cells. CONCLUSIONS: Age is the major relevant factor in
      corneal endothelial cell morphology in patients before cataract surgery.

PMID- 11973384
TI  - Confocal microscopy in Meretoja syndrome.
AB  - PURPOSE: To study the correlation between severity of clinical systemic symptoms
      and the degree of stromal haze and visibility of epithelial and stromal nerves on
      scanning slit confocal microscopy examination in Meretoja syndrome. METHODS:
      Three patients with Meretoja syndrome were examined by slit-lamp microscopy and
      scanning slit confocal microscopy. RESULTS: Increased symptoms and abnormal slit
      lamp findings correlated positively with confocal microscopic stromal haze
      intensity and inversely with visibility of epithelial and stromal nerves on
      confocal examination. A prominent deposit, presumably amyloid, was observed
      contiguous to a stromal nerve of an affected cornea. In a severely affected
      cornea, no stromal or epithelial nerves were seen. CONCLUSION: The results of
      this study suggest that Meretoja syndrome causes corneal nerve damage and
      eventual degeneration that correlates with the degree of clinical involvement.

PMID- 11973385
TI  - Long-term follow-up of intraocular pressure after penetrating keratoplasty for
      keratoconus and Fuchs' dystrophy: comparison of mechanical and Excimer laser
      trephination.
AB  - PURPOSE: In the literature, the incidence of "secondary glaucoma" after
      penetrating keratoplasty (PK) is reported to range from 10% to 42%, depending on
      the diagnosis and the complexity of surgery. The purpose of this study was to
      assess the impact of the trephination method and simultaneous cataract surgery on
      the early and long-term intraocular pressure (IOP) after PK in eyes without
      previous surgery and glaucoma. METHODS: Inclusion criteria for this prospective,
      randomized, longitudinal clinical study were (1) one surgeon (G.O.H.N.), (2)
      primary central PK, (3) Fuchs' dystrophy (7.5/7.6 mm) or keratoconus (8.0/8.1
      mm), and (4) 16-bite double running diagonal suture. Exclusion criteria were (1)
      previous intraocular surgery, (2) preoperative glaucoma, and (3) postoperative
      trauma or endophthalmitis. In 170 patients (mean age, 51 +/- 18 years), PK was
      performed with use of either a 193-nm excimer laser (Excimer patients) along
      metal masks with eight orientation teeth/notches (50 keratoconus, 32 Fuchs') or
      motor trephination (Control patients; 53 keratoconus, 35 Fuchs'). In 27% of
      Excimer patients and 29% of Control patients a triple procedure was performed.
      The perioperative systemic acetazolamide application and the postoperative
      topical steroid therapy were standardized. RESULTS: Maximal IOP during the first
      week after PK was 15.7 +/- 3.6 mm Hg (7% > 21; maximum, 28) in the Excimer group
      and 16.2 +/- 3.5 mm Hg (7% > 21; maximum, 30) in the Control group. During a mean
      follow-up of 3.4 +/- 1.3 years (maximal, 6.0), an IOP >21 mm Hg and/or
      application of topical antiglaucomatous medication was documented in 9% of
      Excimer patients versus 15% of Control patients (p = 0.32), in 15% of Fuchs'
      dystrophy versus 11% of keratoconus cases (p = 0.41), and in 11% of PK-only
      versus 15% of triple-procedure cases (p = 0.68). The IOP elevation started an
      average of 3.7 +/- 2.8 months (1 week to 9 months) after PK and ended an average
      of 6.5 +/- 3.1 months (6 weeks to 12 months) after PK. Mean maximal IOP during
      follow-up was 16.6 +/- 3.5 mm Hg (12-38) in the Excimer group and 17.2 +/- 3.2 mm
      Hg (12-30) in the Control group. Only one patient, who had undergone a triple
      procedure for Fuchs' dystrophy and had an elevated IOP, needed topical
      medication, from 32 months after PK to the end of follow-up. Glaucomatous optic
      disc damage was clinically detected in none of the patients. CONCLUSIONS:
      Temporary secondary ocular hypertension after PK is rare in eyes with keratoconus
      or Fuchs' dystrophy without previous surgery. There was no detectable impact from
      the trephination method, the diagnosis, or simultaneous cataract surgery. With
      meticulous microsurgical technique, careful suturing, and peripheral iridotomy,
      the development of secondary glaucoma with disc cupping seems to be the
      exception.

PMID- 11973386
TI  - Deep lamellar keratoplasty: surgical techniques for anterior lamellar
      keratoplasty with and without baring of Descemet's membrane.
AB  - PURPOSE: To review current techniques used in deep anterior lamellar keratoplasty
      (LKP), and to describe a novel approach that facilitates baring of Descemet's
      membrane (maximum depth anterior lamellar keratoplasty). METHODS: A highly
      selective review of the literature is presented, with descriptions of different
      techniques in the light of the authors' personal experience over 3 decades. A
      novel method for baring Descemet's membrane is detailed. It involves air
      injection in such a way that a large bubble is created between stroma and
      Descemet's membrane. Visual results of this operation in patients with
      keratoconus are reviewed. RESULTS: Visual results 6 months after maximum depth
      anterior LKP in 181 eyes with keratoconus are comparable with those resulting
      from penetrating keratoplasty: 89% achieved a best spectacle-corrected visual
      acuity of 20/40 or better, and 10% achieved 20/20 or better. Intraoperative
      perforation occurred in 9% of cases. CONCLUSIONS: Maximum depth anterior LKP has
      some important advantages when compared with other types of anterior lamellar
      keratoplasty or penetrating keratoplasty, but it remains a challenging procedure.
      A new technique considerably facilitates this operation and reduces
      intraoperative complications.

PMID- 11973387
TI  - Role of choroidal drainage in therapeutic keratoplasty.
AB  - PURPOSE: To discuss the role of choroidal drainage in the management of positive
      vitreous pressure during therapeutic keratoplasty for patients with perforated
      corneal ulcers. METHODS: Over a 2-year period, 8 of 36 (22%) consecutive patients
      with therapeutic grafts presented with a shallow anterior chamber during or
      immediately after surgery. These patients underwent choroidal drainage for
      formation of the anterior chamber. In 5 of them choroidal drainage was done
      intraoperatively when there was significant positive vitreous pressure and the
      anterior chamber could not be formed. Three patients had drainage within a week
      postoperatively for persistent shallow anterior chamber when ultrasonogram showed
      choroidal detachment. RESULTS: Of the eight cases, seven drained fluid and the
      chamber could be reformed well. One was a dry tap and the chamber did not reform
      completely. CONCLUSION: Choroidal detachment (CD) is a previously unpublished
      cause for positive vitreous pressure in therapeutic keratoplasty for perforated
      corneal ulcers. In these situations suprachoroidal drainage can be considered as
      an option for the reformation of the anterior chamber. We recommend that a
      preoperative B-scan ultrasound be included in the workup of all corneal
      perforations and that intraoperative drainage of the fluid is considered in cases
      with significant positive vitreous pressure and confirmed CD.

PMID- 11973388
TI  - Twenty percent alcohol toxicity on rabbit corneal epithelial cells: electron
      microscopic study.
AB  - PURPOSE: To evaluate 20% ethanol toxicity on the rabbit corneal epithelium,
      ethanol-treated rabbit corneas were examined with electron microscopy. METHODS:
      Rabbit corneas (24 eyes) were treated with 20% ethanol for 30 seconds, 1 minute,
      and 2 minutes by using LASEK (laser-assisted subepithelial keratectomy)
      instruments and then washed with sterile water. Zero time, 1, 3, 5 days after
      ethanol treatment, corneas were excised and examined with scanning and
      transmission electron microscopy (SEM and TEM). RESULTS: Widespread partial or
      total damage of microvilli, focal breaks of intercellular junction, and cellular
      edema was observed. The damage was more severe in corneas with longer ethanol
      treatment. In corneas with ethanol treatment more than 1 minute, slough of
      superficial corneal epithelium occurred and progressed with time. Two-minute
      ethanol treatment resulted in complete destruction of microvilli and significant
      separation of intercellular junction. These pathologic changes persisted 5 days
      after ethanol treatment. CONCLUSIONS: From these results, increasing exposure
      time to ethanol more than 1 minute results in significant damage to superficial
      corneal epithelium and prolongs its normal recovery time.

PMID- 11973389
TI  - A photopolymerized sealant for corneal lacerations.
AB  - PURPOSE: To determine whether a novel photocrosslinkable polymer synthesized from
      hyaluronic acid would seal experimental full-thickness corneal lacerations in a
      rabbit model. METHODS: A solution of hyaluronic acid was modified with
      methacrylate groups (HA-MA), precipitated, dried, reconstituted in an aqueous
      solution, and sterilized before use. The viscous polymer solution was applied to
      38 of 43 experimental corneal lacerations in rabbits and subsequently irradiated
      with a low-intensity argon laser beam to produce a clear flexible polysaccharide
      hydrogel patch. The ability of this sealant to repair corneal lacerations was
      evaluated in four types of full-thickness, 3-mm corneal wounds (linear, linear +
      epithelium removed, stellate, and stellate + epithelium removed). Slit-lamp
      examinations, measurements of intraocular pressure, Seidel tests, and histologic
      studies were performed at selected intervals to evaluate the wound and determine
      the rate of healing. RESULTS: Corneal perforations were completely sealed and the
      anterior chambers had reformed by 6 hours in HA-MA-treated eyes. There was no
      evidence of leakage at this or later times in 37 of the 38 eyes. Intraocular
      pressure had risen to near-normal levels by day 7 in all four groups, and the
      sealant was still present in most eyes at day 7. In contrast, the anterior
      chambers did not re-form in control eyes (five) with untreated perforations
      because of aqueous leakage through the wounds. Minimal inflammation was observed
      clinically or in histologic sections of treated corneas. There was extensive
      proliferation of stromal cells and formation of new extracellular matrix at the
      wound edges, which became tightly adherent between days 4 and 7. CONCLUSION: Our
      novel photocrosslinkable methacrylated hyaluronan polymer sealed 97% (37/38) of
      the experimental corneal lacerations. HA-MA may prove useful for sealing corneal
      lacerations in patients and for other sutureless ophthalmic surgical procedures.

PMID- 11973390
TI  - Histopathologic findings in explanted osteo-odontokeratoprosthesis.
AB  - PURPOSE: To report the histologic findings in three explanted osteo
      odontokeratoprosthesis (OOKP) laminae. METHODS: The osteodental lamina of patient
      1 with linear IgA bullous dermatosis had to be explanted 15 months after OOKP
      surgery because of permanent leakage after the resorption of the inferior half of
      the bone/dentin complex. Patient 2 underwent surgery because of corneal blindness
      caused by ocular pemphigoid. The remnants of the osteodental lamina were removed
      after a spontaneous loss of the optic cylinder 30 months after surgery. Patient 3
      showed decentration of the optic cylinder 14 years after OOKP surgery was
      performed because of severe bilateral chemical burn. After intraoperative
      detachment of the optical cylinder from the broken lamina, the keratoprosthesis
      had to be completely removed. All specimens were fixed, decalcified using
      electrolysis, sectioned, and stained with hematoxylin and eosin. RESULTS: All
      three laminae showed some degree of transformation and resorption of dentin and
      bone tissue. An inflammatory reaction could be observed in the laminae of patient
      1 and 2. Downgrowth of keratinizing squamous epithelium and a reduction of bone
      tissue and dentin was found in patient 1. Most of the osteodental lamina of
      patient 2 had been replaced by connective tissue. No signs of acute or chronic
      inflammation could be found in patient 3. The optical cylinder was surrounded by
      a thin layer of connective tissue that was enclosed by a layer of woven bone.
      Dentine was found in just one half of the specimen, adjacent to a partly
      preserved alveolar-dental ligament. CONCLUSION: No conclusive explanation for the
      dissolution of the osteodental lamina in some of the patients can be offered at
      this time, although a few different mechanisms such as epithelial downgrowth
      and/or localized inflammation seem to play a pivotal role. Conversely, the
      preservation of the alveolar-dental ligament seems to be essential for the
      maintenance of the integrity of the OOKP.

PMID- 11973391
TI  - Draining lymph nodes play an essential role in alloimmunity generated in response
      to high-risk corneal transplantation.
AB  - PURPOSE: To further evaluate the role of draining cervical lymph nodes (CLN) in
      high-risk (HR) corneal allografts performed in vascularized beds. Recently, we
      have shown that CLN are critical for promotion of allograft rejection in normal
      risk corneal allografts. METHODS: Fully mismatched HR orthotopic corneal
      transplantation was performed in BALB/c hosts that had their CLN excised before
      transplantation (CLN-). Graft rejection and allospecific delayed-type
      hypersensitivity (DTH) were used as measures of alloreactivity. Numbers of
      interferon gamma (IFN-gamma)- and interleukin 2 (IL-2)-expressing cells were
      compared among hosts that retained their native CLN (CLN+) and CLN-hosts.
      Additionally, splenectomized mice (Sp-), and hosts without either CLN or spleen
      (CLN-Sp-) were evaluated. RESULTS: Within 5 weeks, 100% of HR grafts among CLN+
      hosts were rejected, and hosts of these grafts uniformly demonstrated
      allospecific delayed-type hypersensitivity (DTH). In contrast, 92% of CLN-hosts
      accepted their HR allografts, and demonstrated suppressed allospecific DTH
      response. Moreover, significantly lower numbers of IFN-gamma- and IL-2-expressing
      cells were infiltrating corneal grafts in CLN-group. All Sp-hosts rejected
      corneal allografts in an accelerated manner, whereas 86% of CLN-Sp-hosts accepted
      their allografts indefinitely. CONCLUSIONS: Draining CLN play a critical role in
      alloimmunity and rejection of HR corneal grafts, suggesting the essential
      function of CLN in corneal alloimmunization regardless of the degree of
      preoperative risk. Modulation of factors that regulate access of alloantigens or
      antigen-laden antigen-presenting cells to draining CLN may offer novel strategies
      in controlling induction of alloimmunity in corneal transplantation.

PMID- 11973392
TI  - Nitric oxide generated by corneas in corneal storage media.
AB  - PURPOSE: The purpose of the study was to quantify nitric oxide release by human
      corneal buttons in storage media over time. METHODS: Group 1 consisted of six
      chambers of Optisol GS corneal storage media, each containing a viable human
      corneal button with an attached scleral rim (unsuitable for transplantation),
      sampled at 1-day intervals for at least 17 days (range, 17-28 days). Group 2
      consisted of 34 chambers of Optisol GS media, each used to store a corneal button
      for penetrating keratoplasty, sampled immediately after each surgery. An unused
      vial of Optisol GS storage medium was sampled daily for 17 days to serve as a
      background medium control. The total amount of nitrite and nitrate in each sample
      was determined by a spectrophotometric method based on the Griess reaction.
      RESULTS: Data from the daily sampling in group 1 showed that nitrite and nitrate
      concentrations in storage media containing human corneas increase from a baseline
      level (beginning at the time the corneas are placed in the media) to an
      equilibrium concentration of 2.77 microM in a mean time of 6.15 days. Seventy-six
      percent of the data points from group 2 fell within the 80% predictive interval
      derived from group 1. No nitrite or nitrate was detected in background medium
      control samples. CONCLUSION: The progressive increase in nitrite and nitrate in
      corneal storage media over time suggests that nitric oxide is continuously
      released by corneas during storage before transplantation. Given the toxic free
      radical properties of nitric oxide, corneas in storage media may be subjected to
      the cumulative toxic effects of nitric oxide.

PMID- 11973393
TI  - Transplantation of Descemet's membrane carrying viable endothelium through a
      small scleral incision.
AB  - PURPOSE: To design a technique for transplantation of the Descemet's membrane
      (DM) as a carrier for its endothelium, while maintaining the low-astigmatic
      recipient anterior corneal curvature. METHODS: In a human eye bank eye model,
      recipient eyes (n = 15) had a 5.0-mm scleral tunnel incision made, extending 1.0
      mm into the peripheral cornea. A 9.0-mm-diameter Descemeto rhexis was created,
      i.e., a circular portion of DM was stripped from the posterior stroma. With use
      of a custom-made inserter, a 9.0-mm-diameter donor DM carrying autologous donor
      endothelium was brought into the anterior chamber and positioned against the
      recipient posterior stroma. The procedure was evaluated by keratometry,
      endothelial vital and supravital staining, and light microscopy. RESULTS: Mean
      postoperative astigmatism was 1.0 D (+/-0.6 D). Implanted donor DM showed an
      intact endothelial cell layer, with 3.4% (+/-1.1%) dispersed focal cell death.
      Microscopy showed normal endothelial cell morphology and complete apposition of
      the donor DM against the recipient posterior stroma. CONCLUSIONS: DM can be
      transplanted in vitro with acceptable damage to the donor endothelium and with
      little induced astigmatism.

PMID- 11973394
TI  - Corneal ectasia associated with massage of dacryocystoceles.
AB  - PURPOSE: To report a patient with corneal ectasia and bilateral dacryocystoceles.
      METHODS: Case report, review of medical literature. RESULTS: The patient
      experienced gradual bilateral worsening of visual acuity caused by increasing
      corneal ectasia. Vigorous and frequent massaging of the lacrimal sacs and globes
      preceded development of symptomatic corneal ectasia. CONCLUSIONS: The timing of
      the development of this patient's corneal ectasia suggests an association between
      the dacryocystoceles massage and the ectasia.

PMID- 11973395
TI  - Ultrasonographic biomicroscopic study of an intracorneal hematoma.
AB  - PURPOSE: To demonstrate the importance of ultrasonographic biomicroscopy for
      following the clinical course of an intracorneal hematoma of unknown origin.
      METHODS: A 64-year-old woman was referred to the Nagoya University Hospital
      because of a decrease in vision in her left eye. Her visual acuity was 20/70
      (uncorrectable) in the left eye and the slit-lamp biomicroscopic examination
      showed a dark red-colored intracorneal hematoma in the central area of the left
      eye at the pre-Descemet's membrane level. Because the hematoma was small without
      any epithelial involvement and ultrasonographic biomicroscopy (UBM) and slit-lamp
      biomicroscopy showed a low risk of a pupillary block, she was followed without
      surgical treatment. RESULTS: The hematoma turned yellow and grew smaller, and UBM
      images showed an internal liquified cyst 10 months after her initial visit. The
      cystic legion was detected as a low-echoic cavity by UBM 2 months before it was
      observed by slit-lamp biomicroscopy. The hematoma was almost resolved 2.5 years
      after the onset, and the visual acuity OS improved to 20/30. CONCLUSION: The
      intracorneal hematoma occurred without any obvious cause and should be classified
      as spontaneous. UBM combined with slit-lamp biomicroscopy was useful in
      estimating the extent of the hematoma and thus the risk of pupillary block. It
      was also helpful in deciding whether surgical treatment was necessary.

PMID- 11973396
TI  - Benign lymphoid infiltrate of the iris simulating a malignant melanoma.
AB  - PURPOSE: To report a clinicopathologic correlation of an unusual benign
      lymphocytic iris mass in a patient who had no systemic lymphoproliferative
      disease. METHODS: Case report. RESULTS: A 49-year-old man developed a
      circumscribed, tan lesion in his left iris. The lesion was suspected clinically
      to be an atypical iris melanoma. Histopathologic studies of the resected mass
      revealed a solid tumor that was comprised of lymphocytes and histiocytes.
      Immunohistochemical studies identified that most of the cells were T lymphocytes.
      The histopathologic diagnosis was atypical lymphoid infiltrate. Workup for
      systemic lymphoma and Epstein-Barr virus infection was negative. CONCLUSION:
      Lymphoid infiltrate can manifest as a solitary mass that can simulate an iris
      melanoma.

PMID- 11973398
TI  - In vivo confocal microscopy of patients with amiodarone-induced keratopathy.

PMID- 11973397
TI  - Infectious post-LASIK crystalline keratopathy caused by nontuberculous
      mycobacteria.
AB  - PURPOSE: To report three cases of infectious crystalline keratopathy caused by
      non-tuberculous mycobacteria after LASIK surgery. METHODS: Interventional case
      reports and literature review. RESULTS: Infectious keratitis with clinical
      features of crystalline keratopathy after LASIK is described. Culture revealed
      Mycobacterium chelonae from the corneal scrapings of the three patients, all of
      whom underwent medical and surgical (debridement) treatment. CONCLUSIONS:
      Mycobacteria may cause infectious crystalline keratopathy after LASIK. The
      presence of crystalline keratopathy in patients that underwent LASIK must be
      considered an indicator of nontuberculous mycobacteria infection. Microbiologic
      work-up of a corneal specimen is required for the institution of appropriate
      therapy.

PMID- 11973399
TI  - Perilimbal conjunctival pigmentation in vernal keratoconjunctivitis: a new sign.

PMID- 11973400
TI  - Successful treatment of acute ocular graft-versus-host disease with tacrolimus
      (FK506).

PMID- 11973401
TI  - Temple eye banking in Nepal.

PMID- 11973402
TI  - Management of increased vitreous pressure during penetrating keratoplasty using
      pars plana anterior vitreous aspiration.

PMID- 11973404
TI  - Insulin potentiates bradykinin-induced inositol 1,4,5-triphosphate in neonatal
      rat cardiomyocytes.
AB  - This study investigated whether cross-talk between insulin and the bradykinin
      receptor exists to modulate bradykinin-induced increase in inositol 1,4,5
      triphosphate (IP3) in neonatal rat cardiomyocytes. Treatment of the cultures with
      1, 2, and 20 nM of insulin for 90 min before adding bradykinin increased the IP3
      response to the same bradykinin dose to 372.0 +/- 17.8, 413.7 +/- 17.7, and 457.3
      +/- 18.2 pmol/mg protein, respectively. Tyrphostine A23 and genistein (tyrosine
      kinase inhibitors) decreased the bradykinin (10 nM)-induced IP3 production
      potentiated by 2 nM insulin from 400.7 +/- 19.4 pmol/mg protein to 297.3 +/- 42.4
      and 314.3 +/- 37.5 pmol/mg protein, respectively. Administration of 100 nM N-(6
      aminohexyl)-5-chloro-naphthalenesulfonamide (W7, a calmodulin antagonist)
      significantly increased the bradykinin (10 nM)-induced IP3 production from 311.7
      +/- 13.0 pmol/mg protein in the absence of insulin to 457.8 +/- 19.9, 578.2 +/-
      25.9, and 665.2 +/- 16.0 pmol/mg protein in the presence of 1, 2, and 20 nM
      insulin, respectively. These results demonstrate that cross-talk between the
      insulin receptor and the bradykinin signaling system may exist in neonatal rat
      cardiomyocytes. Tyrosine kinase appears to play an important role in the cross
      talking. Calmodulin controls the IP3 response to bradykinin by a negative
      feedback mechanism.

PMID- 11973405
TI  - Molecular cloning and sequencing of the cDNA for rat mesenteric arterial bed
      elastase-2, an angiotensin II-forming enzyme.
AB  - A 28.5-kD protein expressed in rat mesenteric arterial bed (MAB) perfusate with
      angiotensin II-forming ability was previously characterized. This protein, a
      member of the elastase-2 family of enzymes, seems to be the only representative
      of this family of proteases to be secreted outside the digestive tract and
      implicated in the generation of angiotensin II. The cloning and sequencing of the
      cDNA for the rat MAB elastase-2 by using reverse transcription polymerase chain
      reaction are reported. The sequence of this cDNA was found to be identical to the
      sequence of the rat pancreatic elastase-2; the cDNA is 909 nucleotides in length
      plus a poly (A) tail and encodes a preproenzyme of 271 amino acids. Analysis of
      the putative amino acids in the extended angiotensin I binding site of the rat
      MAB elastase-2 reveals features that could explain the dipeptidyl
      carboxypeptidase-like activity required for efficient conversion of angiotensin I
      to angiotensin II. Additionally, the sequence reveals structural features that
      could contribute to the lack of activity of this enzyme toward angiotensin II.
      Rat MAB elastase-2 was expressed in mesenteric arteries and lung but not in
      aorta. These results may also indicate that rat MAB elastase-2 is expressed in
      resistance vessels but not in conduit vessels.

PMID- 11973406
TI  - Effects of insulin-like growth factor on weight gain in chronic hypoxic rats.
AB  - Chronic hypoxemia has been suggested as the cause of weight loss in malnourished
      patients with chronic obstructive pulmonary disease. Insulin-like growth factor I
      (IGF-I) is believed to improve nitrogen balance and have anabolic effects, and it
      has been proposed as one of the mediators of vascular smooth muscle
      proliferation. The aim of this study was to assess the effects of IGF-I
      administration on the nutritional status and pulmonary vasculature in normoxic
      and chronic hypoxic rats. Twenty rats were randomly assigned to the normoxic (n =
      10) and chronic hypoxic groups (n = 10). They received daily subcutaneous
      injections of either 3.2 mg/kg of recombinant human IGF-I (rhIGF-I) or isotonic
      saline (control group) for 3 weeks. Body weight was greater in IGF-I-treated rats
      compared with vehicle-treated rats, especially during the early and late stages
      of chronic hypoxic exposure, whereas similar weight gain was observed between IGF
      I- and vehicle-treated normoxic rats. In addition, IGF-I treatment increased
      serum total protein and albumin at the end of hypoxic exposure. However, IGF-I
      had no additive effects on the degree of pulmonary hypertension. These results
      indicated that IGF-I promoted anabolism under chronic exposure to hypoxia,
      whereas no adverse effect was observed in the development of pulmonary
      hypertension.

PMID- 11973407
TI  - Differential effects of homocysteine on porcine endothelial and vascular smooth
      muscle cells.
AB  - High concentrations of homocysteine damage endothelial cells and lower
      concentrations increase vascular smooth muscle cell (VSMC) growth. This study
      investigated the effects of various concentrations of homocysteine on endothelial
      cells (VECs) and VSMCs in terms of cell survival, proliferation, and function.
      VECs and VSMCs from porcine thoracic aorta were studied. These cells were exposed
      to homocysteine in concentrations of 20 microM, 400 microM, and 1 mM every 8 h
      for 24 h, and its effect on cell survival, proliferation, and function were
      studied using methylthiazoletetrazolium assay, [3H]-thymidine incorporation test,
      and 6-keto-prostaglandin F1alpha enzyme-linked immunosorbent assay for VECs, and
      platelet-derived growth factor (PDGF) enzyme-linked immunosorbent assay for
      VSMCs, respectively. In VECs, 20 microM of homocysteine reduced the viable cell
      count to 95 +/- 31%, 400 microM reduced it to 89 +/- 35%, 1,000 microM reduced it
      to *58 +/- 29% (control = 100 +/- 30%, n = 18, *p < 0.05). In VSMCs, 20 microM of
      homocysteine slightly increased the viable cell count to 106 +/- 30%, but there
      was no statistical significance; 400 microM of homocysteine reduced the viable
      cell count to *74 +/- 29%, 1,000 microM to *50 +/- 24% (control = 100 +/- 28%, n
      = 18, *p < 0.05). In VECs, 20 microM of homocysteine reduced [3H]-thymidine
      uptake by 98 +/- 14%, 400 microM reduced it by *82 +/- 17%, 1,000 microM reduced
      it by *66 +/- 17% (control = 100 +/- 12, n = 6, *p < 0.05), respectively. But in
      VSMCs, 20 microM of homocysteine significantly increased [3H]-thymidine uptake
      (*131 +/- 16%), and thereafter, homocysteine decreased VSMCs [3H]-thymidine
      uptake, 400 microM by *24 +/- 7%, 1,000 microM by *29 +/- 10% (control = 100 +/-
      16, n = 6, *p < 0.05), respectively. Homocysteine decreased VEC prostacyclin
      secretion in a dose-dependent manner, 20 microM by 105 +/- 0.65 pg/100 microl,
      400 microM by *100 +/- 2.37 pg/100 microl, 1,000 microM by *93 +/- 2.54 pg/100
      microl (control = 107 +/- 1.26 pg/100 microl, n = 6, *p = 0.007). In VSMCs, 20
      microM of homocysteine slightly increased PDGF secretion by 62.2 +/- 20.7 pg/100
      microl, but there was little statistical significance (p = 0.13); 400 microM of
      homocysteine reduced PDGF secretion by *28.9 +/- 10.7 pg/100 microl, and 1,000
      microM reduced it by *21.3 +/- 4.7 pg/100 microl (control = 54.5 +/- 9.3 pg/100
      microl, n = 6, *p < 0.05). High concentrations of homocysteine damaged both VECs
      and VSMCs with respect to cell survival, proliferation, and function. By
      increasing exposure to homocysteine, it was shown that physiologic high
      concentrations of homocysteine enhanced VSMC proliferation.

PMID- 11973408
TI  - Endothelin B receptor-mediated regulation of endothelin-1 content and release in
      cultured porcine aorta endothelial cell.
AB  - Several cardiovascular diseases are associated with an increase in circulating
      levels of endothelin-1 (ET-1). Little is known about the consequences of this
      increase on endothelial cell responses with respect to ET-1 production and
      regulation. Confluent, passage 1, cultured porcine aorta endothelial cells were
      exposed to exogenous ET-1 (0.1 microM) for 24 h. BQ788 (1 microM, ETB receptor
      antagonist) but not BQ123 (1 microM, ETA receptor antagonist) significantly (p <
      0.05) reduced 125I-ET-1 uptake. The effects of BQ788 were mimicked by
      dansylcadaverine (0.5 mM) but not nystatin (50 microg/ml). Immunoreactive ET-1
      endothelial cell content doubled (p < 0.05) after 24 h of exogenous ET-1
      treatment. Bosentan (10 microM, dual ETA/B receptor antagonist) reduced (p <
      0.05) immunoreactive ET-1 content in control cells. Bosentan prevented exogenous
      ET-1-induced endothelial cell ET-1 loading, suggesting that exogenous ET-1 is
      partly recycled. PreproET-1 mRNA levels were reduced (p < 0.05) by exogenous ET-1
      after 24 h, an effect blocked by BQ788 and bosentan. When used alone, both
      receptor antagonists increased mRNA levels. The results of this study suggest
      that part of ET-1 is recycled through ETB receptors and subsequently released to
      contribute to constitutive ET-1 overflow. ET-1 exerts a negative feedback on ET-1
      gene transcription, which is dependent on ETB receptor activation and
      internalization of the complex ET-1/ETB receptor. The maintenance of this
      negative regulatory loop of ET-1 production may be essential for the normal
      endothelial physiology.

PMID- 11973409
TI  - Effects of different tetra-n-alkylammonium ions on acetylcholine-induced
      endothelium-dependent hyperpolarization in rat mesenteric artery.
AB  - The effects of a series of symmetric tetra-n-alkylammonium (TAA) compounds with
      alkyl side chains of one to six carbons in length on acetylcholine-induced
      endothelium-dependent hyperpolarization were examined in rat mesenteric artery.
      All TAA compounds caused a concentration-dependent inhibition of the
      hyperpolarizing response to acetylcholine. The potency of TAAs showed a general
      trend to increase with the lengths of the alkyl side chains. The inhibitory
      effects of TAAs, excepting the smallest compound, on the acetylcholine response
      were reversible. However, TAAs with long alkyl side chains may act as antagonists
      at muscarinic receptors, because the suppressive effect on A23187-induced
      endothelium-dependent hyperpolarization was more marked with TAAs having smaller
      alkyl side chains. Conversely, the hyperpolarizing response to pinacidil, an ATP
      sensitive K+ channel opener, was significantly prevented only by TAA compounds
      with long alkyl side chains. TAA compounds with one-to three-carbon alkyl side
      chains caused a modest and reversible depolarization of the membrane, whereas the
      depolarizing effects of the compounds with four-to six-carbon alkyl side chains
      were marked and irreversible. These results suggest that TAAs could gain access
      to the target K+ channels for endothelium-derived hyperpolarizing factor, the ATP
      sensitive K+ channels, and the K+ channels responsible for the regulation of the
      resting membrane potential in different ways.

PMID- 11973410
TI  - Severity of hypertension affects improved resistance artery endothelial function
      by angiotensin-converting enzyme inhibition.
AB  - The purpose of this study was to determine whether there are differences in the
      restoration of endothelial function by angiotensin-converting enzyme inhibition
      based on the severity of hypertension. Forearm blood flow (FBF) was measured in
      69 patients with essential hypertension (mild, n = 23; moderate, n = 29; and
      severe, n = 17 randomly assigned to treatment with either imidapril or amlodipine
      for 24 weeks in a double-blind fashion during reactive hyperemia and after
      sublingual administration of nitroglycerin. Imidapril augmented the FBF response
      to reactive hyperemia after 24 weeks of treatment in the mild and moderate
      hypertensive groups, but not in the severe hypertensive group. The augmentation
      of the FBF response to reactive hyperemia induced by imidapril was significantly
      greater in the moderate hypertensive group than in the mild hypertensive group.
      Amlodipine did not alter the FBF response to reactive hyperemia. The increase in
      FBF after the sublingually administered nitroglycerin was similar in all groups.
      The infusion of NG-monomethyl-l-arginine, a nitric oxide synthase inhibitor,
      abolished the enhancement of reactive hyperemia in the mild and moderate
      hypertensive groups treated with imidapril. These findings suggest that the
      effects of imidapril on endothelial function are affected by the severity of
      hypertension and that angiotensin-converting enzyme inhibitor-induced
      augmentation of reactive hyperemia may be due to increased nitric oxide
      production.

PMID- 11973411
TI  - Chronic and acute effects of dronedarone on the action potential of rabbit atrial
      muscle preparations: comparison with amiodarone.
AB  - Dronedarone, a noniodinated derivative of amiodarone, is under evaluation as a
      potentially less toxic anti-arrhythmic alternative to amiodarone. The acute and
      chronic electrophysiologic effects of dronedarone and amiodarone were compared in
      isolated rabbit atrial muscle by microelectrode techniques. Four-week PO
      treatment with dronedarone or amiodarone increased action potential duration
      (APD90) (58 +/- 4 ms control versus 69 +/- 2 ms dronedarone, p < 0.01; 68 +/- 3
      ms amiodarone, p < 0.01 for a 100-mg/kg/d dose) and effective refractory period
      (49 +/- 6 ms control versus 68 +/- 4 ms dronedarone, p < 0.01; 63 +/- 3 ms
      amiodarone, p < 0.01). The APD90 prolonged reverse rate-dependency. In contrast,
      acute superfusion with 10 microM dronedarone or amiodarone decreased APD90 (61 +/
      6 ms control versus 53 +/- 4 ms dronedarone, p < 0.05; 52 +/- 6 ms amiodarone, p
      < 0.05), effective refractory period (50 +/- 5 ms control versus 44 +/- 4 ms
      dronedarone, p < 0.05; 43 +/- 6 ms amiodarone, p < 0.05), and the maximum
      upstroke slope of the action potential (Vmax) (188 +/- 9 V/s control versus 182
      +/- 11 V/s dronedarone p < 0.05; 182 +/- 11 V/s amiodarone, p < 0.05). Thus,
      chronic and acute electrophysiologic effects of dronedarone on rabbit atrial
      muscle are similar to those of amiodarone, suggesting a similar potential against
      atrial arrhythmias.

PMID- 11973412
TI  - Role of calcium-activated potassium channels in impaired acetylcholine
      vasodilatory responses in diabetic rats.
AB  - Muscarinic agonists produce endothelium-dependent vasodilatation in the presence
      of nitric oxide synthase (NOS) inhibition. The importance of this mechanism was
      assessed in the methoxamine-preconstricted perfused mesenteric vascular bed (MVB)
      of streptozotocin diabetic Sprague-Dawley rats. At 9 weeks of age, male rats were
      treated with streptozotocin (55 mg/kg in citrate buffer) or with citrate buffer
      alone. The superior mesenteric artery was cannulated and the MVB was detached
      from its intestinal borders. Concentration-response curves to acetylcholine were
      determined in the presence and in the absence of indomethacin, tetrabutylammonium
      (a calcium-activated potassium channel blocker), high extracellular potassium, or
      NOS inhibition with Nomega-nitro-l-arginine and l-NG-nitro-l-arginine. There was
      a rightward shift in the concentration-response curve with an increase in median
      inhibitory concentration (p < 0.05) and a reduction in acetylcholine IMAX (p <
      0.05) values in 14-week streptozotocin rats. The ability of NOS inhibition to
      attenuate vasodilatation was reduced in the 14-week streptozotocin group relative
      to the 2-week streptozotocin treatment group (p < 0.05). However, the ability of
      tetrabutylammonium to block acetylcholine-mediated vasodilatation remained
      consistent in streptozotocin rats at both stages. The results demonstrate that an
      alternate pathway involving calcium-activated potassium channels may compensate
      for diminished nitric oxide bioactivity. This effect is contingent on the
      duration of diabetes. This study provides insight into the development and
      progression of altered diabetic vascular responses.

PMID- 11973413
TI  - Acute and chronic treatment with nicotine impairs reactivity of arterioles in
      response to activation of potassium channels.
AB  - Although acute and chronic treatment with nicotine impairs nitric oxide synthase
      dependent responses of large and small blood vessels, the effect of nicotine on
      other vasodilator pathways remains uncertain. The goal of the current study was
      to determine effects of nicotine on dilatation of arterioles to activation of ATP
      sensitive potassium channels. Reactivity of cheek pouch arterioles (
      approximately 50 microm) was measured during acute (1-2 h) and chronic (2-to 3
      week) exposure to nicotine in response to aprikalim, cromakalim, and
      nitroglycerin. Acute treatment with nicotine impaired dilatation of arterioles in
      response to aprikalim and cromakalim but not nitroglycerin. Aprikalim and
      cromakalim (1.0 microM) dilated arterioles by 37 +/- 5% and 30 +/- 3%,
      respectively, before, but by only 21 +/- 4% and 16 +/- 3%, respectively, after
      infusion of nicotine (p < 0.05). Chronic exposure to nicotine did not alter
      vasodilatation to nitroglycerin but impaired vasodilatation to aprikalim and
      cromakalim. In vehicle-treated hamsters, aprikalim and cromakalim (1.0 microM)
      dilated arterioles by 28 +/- 1% and 32 +/- 3%, respectively. However, in nicotine
      treated hamsters aprikalim and cromakalim (1.0 microM) dilated arterioles by only
      3 +/- 1% and 13 +/- 1%, respectively. Next, the role of superoxide anion in
      impaired responses of arterioles to aprikalim and cromakalim during acute
      infusion of nicotine was examined. Treatment with superoxide dismutase attenuated
      the effects of nicotine on aprikalim and cromakalim. Thus, acute and chronic
      exposure to nicotine has profound affects on vasodilatation to activation of ATP
      sensitive potassium channels, which may be mediated by superoxide anion.

PMID- 11973414
TI  - Mechanism of raloxifene-induced relaxation in femoral veins depends on ovarian
      hormonal status.
AB  - Experiments were designed to study effects of raloxifene, a selective estrogen
      receptor modulator, on venous endothelium and smooth muscle. Rings of femoral
      veins with and without endothelium from adult gonadally intact, and
      ovariectomized female pigs were suspended for measurement of isometric force in
      organ chambers. Concentration-response curves to raloxifene (10-9-10-5 M) were
      obtained in rings at baseline tension or following contraction with prostaglandin
      (2 x 10-6 M) in the absence or presence of NG-monomethyl-l-arginine (l-NMMA)
      (nitric oxide synthase inhibitor), 1H-(1.2.4) oxadiazolo (4,3-A) quinoxalin-1-one
      (ODQ, soluble guanylate cyclase inhibitor), tetraethylammonium acetate (TEA;
      potassium channel blocker), or indomethacin (cyclooxygenase inhibitor).
      Raloxifene caused acute, concentration-dependent relaxations that were greater in
      rings with than in rings without endothelium from both groups. The l-NMMA
      significantly inhibited relaxations to raloxifene in rings with endothelium from
      ovariectomized females whereas TEA only inhibited relaxations in rings with
      endothelium from intact female pigs. ODQ and indomethacin significantly inhibited
      relaxations in rings with endothelium from both groups. These results suggest
      that raloxifene acutely relaxes femoral veins through release of endothelium
      derived factors and by direct stimulation of vascular smooth muscle cells.
      Whether nitric oxide or potassium channel activation contributes to relaxations
      by raloxifene may depend on ovarian hormonal status of the animal.

PMID- 11973415
TI  - Mixed tocopherols have a stronger inhibitory effect on lipid peroxidation than
      alpha-tocopherol alone.
AB  - Intake of vitamin E with food (mixed tocopherols) has been found to counteract
      the development of atherosclerotic cardiovascular disease, whereas intake of
      large amounts of pure alpha-tocopherol has shown only a slight or no effect in
      clinical studies. This study was designed to investigate the effects of alpha
      tocopherol alone and a mixed tocopherol preparation (gamma-, delta-, and alpha
      tocopherol) on hydrogen peroxide-induced lipid peroxidation in human
      erythrocytes. Erythrocytes were incubated with different concentrations of alpha
      tocopherol or mixed tocopherols and then exposed to hydrogen peroxide. Tocopherol
      levels and malondialdehyde-thiobarbituric acid-reactive substances were
      determined by high-performance liquid chromatography and fatty acids by gas
      chromatography. Incubation of erythrocytes with tocopherols (30-120 microM)
      increased the tocopherol level in a concentration-dependent manner. The uptake of
      gamma- and delta-tocopherols was much higher than that of alpha-tocopherol.
      Hydrogen peroxide strongly increased lipid peroxidation and decreased
      polyunsaturated fatty acids in erythrocytes. Both alpha-tocopherol and the
      tocopherol mixture protected the cells from lipid peroxidation, the mixture being
      much more potent than alpha-tocopherol alone. This study indicates that a mixture
      of tocopherols has a stronger inhibitory effect on lipid peroxidation induced in
      human erythrocytes than alpha-tocopherol alone, due to higher uptake of gamma-
      and delta-tocopherol in the cells.

PMID- 11973416
TI  - Attenuation of trace element-mediated injury during ischemia and reperfusion by
      an N-terminus analogue of human albumin (H4DUS60131).
AB  - The N-terminus region of human albumin binds strongly to trace metals (Co, Cu,
      Ni). Ischemia, acidosis and reperfusion can cause a marked increase in plasma
      free Cu and its normal regulation by plasma proteins may be overwhelmed and
      predispose to oxidative injury by Cu-catalyzed oxyradical production. H4DUS60131
      is an analogue of the N-terminus of human albumin, it binds copper tightly and in
      vitro, is a potent inhibitor of Cu-catalyzed radical formation. We have tested
      the ability of H4DUS60131 to reduce injury during ischemia and reperfusion in
      isolated blood-perfused rat hearts (n = 6/group) subjected to 20-min aerobic
      perfusion, followed by a 2-min infusion of saline or saline plus H4DUS60131.
      Following infusion, hearts were subjected to 30-min global ischemia plus 40-min
      reperfusion. The 2-min infusion was repeated in both groups at the start of
      reperfusion. In the vehicle controls, left ventricular developed pressure
      recovered to only 15.3 +/- 3.2%, whereas the H4DUS60131 group recovered to 50.5
      +/- 9.3% (p < 0.005). The H4DUS60131 group normalised their left ventricular end
      diastolic pressure more quickly and completely than the controls (44.1 +/- 11.5
      vs. 91.5 +/- 5.5 mm Hg). In conclusion, H4DUS60131 greatly improves the recovery
      of the rat heart from ischemia and reperfusion and may represent a novel approach
      to the limitation of myocardial injury.

PMID- 11973418
TI  - Inhibition of vascular smooth muscle cell growth by angiotensin type 2 receptor
      stimulation for in vitro organ culture model.
AB  - Recent data suggest that AT2 receptors in smooth muscle cells (VSMCs) of adult
      vessels may counterbalance AT1 receptor activity by inhibiting cell growth. The
      role of AT2 receptors in VSMC proliferation was investigated by using an in vitro
      organ culture model in which the sprouting of tubular structures was assessed. In
      preparations with endothelium, tubular growth was unaffected by angiotensin II
      (Ang II) but was inhibited by 50 +/- 9% by losartan and was increased by 110 +/-
      15% by the AT2 antagonist PD123177. In endothelium-deprived preparations, growth
      inhibition (-49.1 +/- 0.5%) was observed when angiotensin II was added together
      with losartan 1 microM, whereas stimulation (59.8 +/- 14%) was induced by
      angiotensin II with 1 microM PD123177. In cultured VSMCs angiotensin II slightly
      promoted growth that was inhibited by losartan but was unaffected by PD123177.
      AT1a, AT1b, and AT2 mRNA expression was demonstrated in cells isolated from
      tubular structures grown from intact and endothelium-deprived rings, but only
      AT1a and AT1b mRNA was detected in cultured VSMCs. In conclusion, this paper
      proposes an in vitro organ culture model in which the expression of AT2 receptors
      in VSMCs is preserved and demonstrates AT2 receptor-mediated inhibition of VSMC
      proliferation in adult vessels.

PMID- 11973417
TI  - Inhibitory effect of activated protein C on cerebral vasospasm after subarachnoid
      hemorrhage in the rabbit.
AB  - This study investigated whether activated protein C (APC) improves the cerebral
      vasospasm in an experimental subarachnoid hemorrhage that was produced by the
      intracisternal injection of autologous blood. Male rabbits were divided into the
      following four groups: APC 0.1-and 0.5-mg groups, in which 0.1 and 0.5 mg APC
      were injected into the cisterna magna, respectively; a placebo group, in which
      saline was injected instead of APC; and a sham operation group that did not get
      injections of autologous blood, APC, and saline. On day 2, amount of clot in the
      basal cistern was significantly (p < 0.01) decreased in the APC 0.5-mg group.
      Percent diameter of the basilar artery on day 2 to that before injecting the
      blood was angiographically determined as 97.1 +/- 3.8% in the APC 0.5-mg group,
      which was significantly (p < 0.001) greater than the corresponding value in the
      placebo group (74.8 +/- 3.4%). The impaired endothelium-dependent relaxation
      following subarachnoid hemorrhage was normalized in the APC 0.5-mg group (p <
      0.0001). These results suggest that APC would improve cerebral vasospasm
      following subarachnoid hemorrhage, possibly by decreasing the amount of
      subarachnoid clot and normalizing the impaired nitric oxide production/release.

PMID- 11973419
TI  - Early anti-remodeling effect of labetalol in the congestive heart failure model
      induced by aortic constriction in the guinea pig.
AB  - We investigated the effects of the beta1-beta2-alpha1-blocker, labetalol, in the
      congestive heart failure (CHF) model induced by aortic constriction in the guinea
      pig. One hundred days after aortic constriction, 52 animals were given either
      placebo, labetalol 2 mg/kg/d, or labetalol 20 mg/kg/d for 60 days. Eighteen sham
      operated animals were used as controls. Investigations were performed at the end
      of the treatment period. Compared with sham-operated animals, banded animals
      receiving placebo showed signs of overt CHF with cardiac, systemic and regional
      (mesenteric and femoral) hemodynamic dysfunction, and pulmonary and hepatic
      congestion. An increase in whole heart, atria, and left and right ventricle
      weights associated with left ventricular cavity enlargement and left and right
      ventricular wall thickening indicated a remodeling process. Compared with
      placebo, labetalol did not significantly modify cardiac, systemic, or regional
      hemodynamic variables but significantly decreased pulmonary and hepatic
      congestion. Labetalol significantly reduced left ventricular cavity area (-10 and
      -20% after 2 and 20 mg/kg, respectively) and left ventricular (-4 and -16%) and
      right ventricular (-4 and -19%) wall thickness. In conclusion, labetalol induced
      partial regression of cardiac remodeling before hemodynamic improvement. This
      early anti-remodeling effect could play a role in the favorable effects observed
      with beta1-beta2-alpha1-blockers in humans.

PMID- 11973420
TI  - Intravenous adrenomedullin in myocardial function and energy metabolism in
      patients after myocardial infarction.
AB  - This study investigated the effects of adrenomedullin on left ventricular
      myocardial contraction and relaxation, coronary blood flow, and myocardial oxygen
      consumption in comparison with those of atrial natriuretic peptide (ANP).
      Fourteen patients who had had myocardial infarctions were randomly assigned to
      receive IV infusion of adrenomedullin (0.05 microg/kg/min) or ANP (0.05
      microg/kg/min). Both adrenomedullin and ANP significantly decreased left
      ventricular systolic pressure (-17 mm Hg, -13 mm Hg, respectively, both p <
      0.05). The increase in cardiac index by adrenomedullin (+31%) was significantly
      greater than that by ANP (+16%). Adrenomedullin significantly increased an index
      of myocardial contractility, Emax (2.5 +/- 0.3 mm Hg-3.7 +/- 0.3 mm Hg/ml, p <
      0.05) and shortened an index of myocardial relaxation, Tau (52 +/- 5 ms-48 +/- 4
      ms, p < 0.05). In contrast, ANP did not significantly alter either parameter. In
      addition, adrenomedullin, but not ANP, significantly increased coronary sinus
      blood flow (73 +/- 10 ml/min-86 +/- 10 ml/min, p < 0.05). Adrenomedullin did not
      increase myocardial oxygen consumption. Unlike ANP, IV administration of
      adrenomedullin enhanced left ventricular myocardial contraction and improved left
      ventricular relaxation without increasing myocardial oxygen consumption in
      patients who had had a myocardial infarction.

PMID- 11973421
TI  - Preconditioning attenuates the shortening of recovery during coronary occlusion
      in isolated rabbit hearts with D-sotalol-induced long QT intervals.
AB  - The effects of 20-min ligations of the anterior branch of the left coronary
      artery were studied in Langendorff-perfused rabbit hearts with 92 microM D
      sotalol added to the perfusate to induce long QT intervals and triggered
      arrhythmias. Epicardial electrograms, a left ventricular endocardial monophasic
      action potential, and simulated X and Y lead electrocardiograms were used to
      characterize ventricular conduction and recovery. In contrast to previous work
      showing that global ischemia eliminated triggered activity, coronary occlusion
      did not alter its mean incidence. Although the anatomic distribution of earliest
      sites of epicardial activation by triggered beats was altered, triggered beats
      still appeared on the epicardial surface in the nonperfused regions. Coronary
      occlusion had a small and variable effect on epicardial conduction velocity but
      caused a significantly greater percent shortening of epicardial activation
      recovery intervals in the nonperfused region of hearts given D-sotalol than in
      control hearts. In hearts given D-sotalol, preconditioning significantly
      attenuated the shortening of epicardial activation-recovery intervals in response
      to coronary occlusion. However, preconditioning had no effect on the mean
      incidence of triggered activity during coronary occlusion. Thus, the persistence
      of triggered activity and the shortened myocardial recovery time associated with
      coronary occlusion could contribute to increasing the likelihood of occurrence of
      malignant ventricular arrhythmias. Preconditioning by attenuating the shortening
      of recovery would be anti-arrhythmic.

PMID- 11973422
TI  - Hematopoietic factor erythropoietin fosters neuroprotection through novel signal
      transduction cascades.
AB  - In addition to promoting the survival, proliferation, and differentiation of
      immature erythroid cells, erythropoietin and the erythropoietin receptor have
      recently been shown to modulate cellular signal transduction pathways that extend
      beyond the erythropoietic function of erythropoietin. In particular,
      erythropoietin has been linked to the prevention of programmed cell death in
      neuronal systems. Although this work is intriguing, the underlying molecular
      mechanisms that serve to mediate neuroprotection by erythropoietin are not well
      understood. Further analysis illustrates that erythropoietin modulates two
      distinct components of programmed cell death that involve the degradation of DNA
      and the externalization of cellular membrane phosphatidylserine residues.
      Initiation of the cascades that modulate protection by erythropoietin and its
      receptor may begin with the activation of the Janus tyrosine kinase 2 protein.
      Subsequent downstream mechanisms appear to lead to the activation of multiple
      signal transduction pathways that include transcription factor STAT5 (signal
      transducers and activators of transcription), Bcl-2, protein kinase B, cysteine
      proteases, mitogen-activated protein kinases, protein-tyrosine phosphatases, and
      nuclear factor-kappaB. New knowledge of the cellular pathways regulated by
      erythropoietin in neuronal environments will potentially solidify the development
      and initiation of therapeutic strategies against nervous system disorders.

PMID- 11973423
TI  - Nitric oxide does not inhibit cerebral cytochrome oxidase in vivo or in the
      reactive hyperemic phase after brief anoxia in the adult rat.
AB  - In this study, near-infrared spectroscopy was applied to examine whether
      cytochrome oxidase in the rat brain is inhibited by nitric oxide in vivo. During
      normoxia, intravenous N(G)-nitro-L-arginine methyl ester (L-NAME) administration
      significantly decreased the cerebral saturation of hemoglobin with oxygen but did
      not alter the cytochrome oxidase redox state. Anoxia significantly reduced the
      cytochrome oxidase. The time course of the recovery of the redox state during
      reoxygenation was not altered by L-NAME. The results suggest that in adult rats,
      cytochrome oxidase is not inhibited by nitric oxide, either in physiologic
      conditions or during reoxygenation after a brief anoxic period.

PMID- 11973424
TI  - Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and
      in vitro.
AB  - The widely prescribed drug desferrioxamine is a known activator of the hypoxia
      inducible transcription factor 1 (HIF-1) and the subsequent transcription of
      erythropoietin. In the brain, HIF-1 is a master switch of the transcriptional
      response to hypoxia, whereas erythropoietin is a potent neuroprotectant. The
      authors show that desferrioxamine dose-dependently and time-dependently induces
      tolerance against focal cerebral ischemia in rats and mice, and against oxygen
      glucose deprivation in purified cortical neurons. Desferrioxamine induced HIF-1
      DNA binding and transcription of erythropoietin in vivo, the temporal kinetics of
      which were congruent with tolerance induction. Desferrioxamine is a promising
      drug for the induction of tolerance in humans when ischemia can be anticipated.

PMID- 11973425
TI  - Microvascular basal lamina injury after experimental focal cerebral ischemia and
      reperfusion in the rat.
AB  - To define the location and extent of microvascular damage of the basal lamina
      after cerebral ischemia and reperfusion in rats, the authors subjected animals (n
      = 16) to 3 hours of focal cerebral ischemia and 24 hours of reperfusion using the
      suture middle cerebral artery occlusion model; sham-operated animals served as
      controls (n = 6). The Western blot technique was used to define the collagen type
      IV protein content in various brain regions, whereas immunohistochemistry
      identified microvascular basal lamina loss (anticollagen type IV staining). The
      extent of damage was quantified by automatic morphometric video-imaging analysis.
      Statistical analysis was based on the Mann-Whitney test and the paired Student's
      t-test. The ischemic hemisphere showed a reduction of the collagen type IV
      protein content after ischemia and reperfusion in the Western blot (reduction
      compared with the nonischemic side: total hemisphere, 33% +/- 6%; basal ganglia,
      25% +/- 7%; cortex 49% +/- 4%; P < 0.01) [corrected]. There was also a decrease
      in the number of cerebral microvessels between the ischemic and nonischemic
      hemispheres (20% +/- 2%), cortical (8% +/- 3%), and basal ganglia areas (31% +/-
      3%) (P < 0.001). Besides a reduction of the vessel number, there was also a loss
      in basal lamina antigen-positive stained area in ischemic areas (hemisphere, 16%
      +/- 3%; cortex, 14% +/- 3%; basal ganglia, 21% +/- 4%; P < 0.01) [corrected].
      Cortical areas had a less pronounced basal lamina loss than basal ganglia (P <
      0.05). For the first time, microvascular basal lamina damage, indicated by
      collagen type IV loss, is proven in rats by biochemical and morphometric
      analysis. These changes are comparable with those found in nonhuman primates. The
      authors report novel data regarding microvascular ischemic changes in the cortex.
      These data provide a basis for future experiments to determine the mechanisms of
      ischemic microvascular damage and to devise new therapeutic strategies.

PMID- 11973426
TI  - Cloning and characterization of rat caspase-9: implications for a role in
      mediating caspase-3 activation and hippocampal cell death after transient
      cerebral ischemia.
AB  - Delayed hippocampal neurodegeneration after transient global ischemia is
      mediated, at least in part, through the activation of terminal caspases,
      particularly caspase-3, and the subsequent proteolytic degradation of critical
      cellular proteins. Caspase-3 may be activated by the membrane receptor-initiated
      caspase-8-dependent extrinsic pathway and the mitochondria-initiated caspase-9
      dependent intrinsic pathway; however, the precise role of these deduced apoptosis
      signaling pathways in activating caspase-3 in ischemic neurons remains elusive.
      The authors cloned the caspase-9 gene from the rat brain and investigated its
      potential role in mediating ischemic neuronal death in a rat model of transient
      global ischemia. Caspase-9 gene expression and protease activity were extremely
      low in the adult brain, whereas they were developmentally upregulated in newborn
      rats, especially at postnatal 12 weeks, a finding consistent with the theory of
      an essential role for caspase-9 in neuronal apoptosis during brain development.
      After 15-minute transient global ischemia, caspase-9 was overexpressed and
      proteolytically activated in the hippocampal CA1 neurons at 8 to 72 hours of
      reperfusion. The temporal profile of caspase-9 activation coincided with that of
      cytochrome c release and caspase-3 activation, but preceded CA1 neuronal death.
      Immunoprecipitation experiments revealed that there was enhanced formation of
      Apaf-1/caspase-9 complex in the hippocampus 8 and 24 hours after ischemia.
      Furthermore, intracerebral ventricular infusion of the relatively specific
      caspase-9 inhibitor N-benzyloxycarbonyl-Leu-Glu-His-Asp-fluoro-methylketone
      before ischemia attenuated caspase-3-like activity and significantly enhanced
      neuronal survival in the CA1 sector. In contrast, inhibition of caspase-8
      activity had no significant effect on caspase-3 activation or neuronal survival.
      These results suggest that the caspase-9-dependent intrinsic pathway may be the
      primary mechanism responsible for the activation of caspase-3 in ischemic
      hippocampal neurons.

PMID- 11973427
TI  - Quantitative T(1rho) and magnetization transfer magnetic resonance imaging of
      acute cerebral ischemia in the rat.
AB  - It has been previously shown that T1 in the rotating frame (T(1rho)) is a very
      sensitive and early marker of cerebral ischemia and that, interestingly, it can
      provide prognostic information about the degree of subsequent neuronal damage. In
      the present study the authors have quantified T(1rho) together with the rate and
      other variables of magnetization transfer (MT) associated with spin interactions
      between the bulk and semisolid macromolecular pools by means of Z spectroscopy,
      to examine the possible overlap of mechanisms affecting these magnetic resonance
      imaging contrasts. Substantial prolongation of cerebral T(1rho) was observed
      minutes after induction of ischemia, this change progressing in a time-dependent
      manner. Difference Z spectra (contralateral nonischemic minus ischemic brain
      tissue) showed a significant positive reminder in the time points from 0.5 to 3
      hours after induction of ischemia, the polarity of this change reversing by 24
      hours. Detailed analysis of the MT variables showed that the initial Z spectral
      changes were due to concerted increase in the maximal MT (+3%) and amount of MT
      (+4%). Interestingly, the MT rates derived either from the entire frequency range
      of Z spectra or the time constant for the first-order forward exchange (k(sat))
      were unchanged at this time, these variables reducing only one day after
      induction of ischemia. The authors conclude that T(1rho) changes in the acute
      phase of ischemia coincide with both elevated maximal MT and amount of MT. These
      changes occur independent of the overall MT rate and in the absence of net water
      gain to the tissue, whereas in the consolidating infarction the decrease in the
      rate and amount of MT, as well as the extensive prolongation of T(1rho), are
      associated with water accumulation.

PMID- 11973429
TI  - Delayed anoxic depolarizations in hippocampal neurons of mice lacking the
      excitatory amino acid carrier 1.
AB  - Hypoxia leads to a rapid increase in vesicular release of glutamate. In addition,
      hypoxic glutamate release might be caused by reversed operation of neuronal
      glutamate transporters. An increase in extracellular glutamate concentration
      might be an important factor in generating anoxic depolarizations (AD) and
      subsequent neuronal damage. To study the AD and the vesicular release in
      hippocampal slices from CD1 wild-type mice and mice in which the neuronal
      glutamate transporter excitatory amino acid carrier 1 (EAAC1) had been knocked
      out, the authors performed recordings of field potentials and patch clamp
      recordings of CA1 pyramidal cells. Latency to anoxic depolarizations was enhanced
      in EAAC1-/- mice, whereas the hypoxia-induced increase in miniature excitatory
      postsynaptic current frequency occurred with similarly short latencies and to a
      similar extent in control and mutated animals. Additional block of glial
      glutamate uptake with TBOA (dl-threo-beta-benzyloxyaspartate), a nontransportable
      and potent inhibitor, dramatically reduced the latency to onset of AD and
      abolished the difference between wild-type mice and EAAC1-/- mice. The authors
      conclude that the neuronal glutamate transporter greatly influences the latency
      to generation of AD. Because ADs are not prevented in EAAC1-deficient mice,
      vesicular release mechanisms also seem to be involved. They become prominent when
      glial glutamate transport is blocked.

PMID- 11973428
TI  - Magnetic resonance imaging characterization of hemorrhagic transformation of
      embolic stroke in the rat.
AB  - Intracranial hemorrhage is a critical factor when considering efficacy and safety
      of thrombolytic intervention after thromboembolic stroke. This study tested
      whether magnetic resonance imaging could identify tissue for hemorrhagic
      transformation after the onset of embolic stroke. Rats subjected to embolic
      stroke with and without recombinant tissue-type plasmogen activator (rt-PA)
      treatment were followed-up with magnetic resonance imaging using the inverse of
      the apparent forward transfer rate for magnetization transfer (k(inv)),
      gadolinium-chelate contrast-enhanced magnetic resonance imaging, and diffusion-,
      perfusion-, and T2-weighted imaging. Rats with embolic stroke either were treated
      with rt-PA 1 (n = 16) or 4 hours (n = 13) after stroke onset or were not treated
      (n = 15). From these groups, at total of 17 rats had intracerebral hemorrhage.
      Tissue progressing to hemorrhage and adjacent to the site of hemorrhage was
      analyzed to identify magnetic resonance imaging markers that characterize
      hemorrhagic transformation. The parameter maps of k(inv) and contrast-enhanced
      magnetic resonance imaging showed greater sensitivity in the detection of tissue
      destined for hemorrhagic transformation compared with the apparent diffusion
      coefficient of water (ADCw) and CBF. In tissue not destined to undergo
      hemorrhagic transformation, k(inv) maps and contrast-enhanced magnetic resonance
      imaging exhibited small increases in k(inv) and contrast-enhanced magnetic
      resonance imaging signal intensity in the area encompassing the territory
      supplied by the middle cerebral artery. In contrast, large increases in k(inv)
      and in signal intensity in the contrast-enhanced magnetic resonance images were
      detected in the region where gross hemorrhage was confirmed histologically. The
      values of k(inv), T2, and signal intensity in the contrast-enhanced magnetic
      resonance images were significantly higher in the region destined for hemorrhagic
      transformation (k(inv), P < or = 0.033 3-24 hours after embolization; T2, P < or
      = 0.037 24-48 hours; contrast-enhanced magnetic resonance imaging, P < 0.05 4-7
      hours) compared with the nonhemorrhagic transformation ischemic region or in the
      contralateral homologous regions after onset of ischemia. Of these methods,
      k(inv) shows the most sensitivity in the detection of hemorrhagic transformation
      soon after embolization. The authors' data suggest that k(inv) and contrast
      enhanced magnetic resonance imaging are potentially important methodologies for
      detecting tissue destined for hemorrhagic transformation.

PMID- 11973430
TI  - TACE/ADAM17-TNF-alpha pathway in rat cortical cultures after exposure to oxygen
      glucose deprivation or glutamate.
AB  - The role of the tumor necrosis factor (TNF)-alpha convertase (TACE/ADAM17) in the
      adult nervous system remains poorly understood. The authors have previously
      demonstrated that TACE is upregulated in rat forebrain slices exposed to oxygen
      glucose deprivation (OGD). They have now used rat mixed cortical cultures exposed
      to OGD or glutamate to study (1) TACE expression and localization, and (2) the
      effects of TNF-alpha release on cell viability. OGD-or glutamate-caused TNF-alpha
      release, an effect that was blocked by the TACE inhibitor BB3103 (BB) (0.1-1
      micromol/L; control: 1.67 +/- 0.59; OGD: 6.59 +/- 1.52; glutamate: 3.38 +/- 0.66;
      OGD +/- BB0.1: 3.23 +/- 0.67; OGD +/- BB1: 1.33 +/- 0.22 pg/mL, n = 6, P < 0.05).
      Assay of TACE activity as well as Western blot showed that TACE expression is
      increased in OGD-or glutamate-exposed cells. In control cultures, TACE
      immunoreactivity was present in some microglial cells, whereas, after OGD or
      glutamate, TACE immunostaining appeared in most microglial cells and in some
      astrocytes. Conversely, BB3103 (0.1 micromol/L) caused apoptosis after glutamate
      exposure as shown by annexin and Hoechst 33342 staining and caspase-3 activity,
      an effect mimicked by the proteasome inhibitor MG-132 (caspase activity:
      glutamate: 5.1 +/- 0.1; glutamate + BB: 7.8 +/- 0.8; glutamate + MG: 11.9 +/- 0.5
      pmol. min(-1) mg(-1) protein, n = 4, P < 0.05), suggesting that translocation of
      the transcription factor NF-kappaB mediates TNF-alpha-induced antiapoptotic
      effect. Taken together, these data demonstrate that, in rat mixed neuronal-glial
      cortical cultures exposed to OGD or glutamate, (1) TACE/ADAM17 activity accounts
      for the majority of TNF-alpha shedding, (2) an increase in glial TACE expression
      contributes to the rise in TNF-alpha, and (3) TNF-alpha release in this setting
      inhibits apoptosis via activation of the transcription factor NF-kappaB.

PMID- 11973431
TI  - MCT2 is a major neuronal monocarboxylate transporter in the adult mouse brain.
AB  - Although previous Northern blot and in situ hybridization studies suggested that
      neurons express the monocarboxylate transporter MCT2, subsequent
      immunohistochemical analyzes either failed to confirm the presence of this
      transporter or revealed only a low density of immunolabeled neuronal processes in
      vivo. The authors report that appropriate section pretreatment (brief warming
      episode or proteinase K exposure) leads to extensive labeling of the neuropil,
      which appears as tiny puncta throughout the whole mouse brain. In addition,
      intense MCT2 immunoreactivity was found in cerebellar Purkinje cell bodies and
      their processes, on mossy fibers in the cerebellum, and on sensory fibers in the
      brainstem. Double immunofluorescent labeling with appropriate markers and
      observation with epifluorescence and confocal microscopy did not show extensive
      colocalization of MCT2 immunoreactivity with presynaptic or postsynaptic
      elements, but colocalization could be observed occasionally in the cortex with
      the postsynaptic density protein PSD95. Observations made at the electron
      microscopic level in the cortex corroborated these results and showed that MCT2
      immunoreactivity was associated with wide membrane segments of neuronal
      processes. These data provide convincing evidence that MCT2 represents a major
      neuronal monocarboxylate transporter in the adult mouse brain, and further
      suggest that mature neurons could use monocarboxylates such as lactate as
      additional energy substrates.

PMID- 11973432
TI  - Specific binding of [(11)C]raclopride and N-[(3)H]propyl-norapomorphine to
      dopamine receptors in living mouse striatum: occupancy by endogenous dopamine and
      guanosine triphosphate-free G protein.
AB  - According to the ternary complex model of G-protein linkage to receptors,
      agonists increase the affinity of the receptors for the G protein. The model
      predicts that an endogenous agonist's constant of inhibition toward an agonist
      radioligand is lower than that toward an antagonistic radioligand. The authors
      hypothesized that competition from endogenous dopamine in striatum of living mice
      should have a greater effect on the binding of the D2,3 partial agonist N
      [3H]propylnorapomorphine than on the binding of the D2,3 antagonist
      [(11)C]raclopride. The baseline binding potential (pB(0)), defined as the ratio
      of bound-to-unbound ligand in the absence of competition from endogenous
      dopamine, was simultaneously measured in mouse striatum for [(11)C]raclopride
      (pB(0) = 8.5) and N-[(3)H]propylnorapomorphine (p'B(0) = 5.3). The baseline was
      established by treatment with alpha-methyl-p-tyrosine and reserpine. Relative to
      these baseline values in saline-treated mice, the pB of N
      [(3)H]propylnorapomorphine decreased 52% whereas the pB of [(11)C]raclopride
      decreased only 30%, indicating greater sensitivity of the former compound to
      inhibition by synaptic dopamine. Furthermore, amphetamine decreased the pB of N
      [(3)H]propylnorapomorphine to a greater extent (73%) than that of
      [(11)C]raclopride (43%) relative to the reserpine condition. For both
      radioligands, the occupancy of the dopamine receptors by endogenous agonist
      obeyed Michaelis-Menten kinetics over a wide range of agonist concentrations
      established by the pharmacologic treatments. The apparent inhibition constant of
      endogenous dopamine depended on the dopamine occupancy and decreased to a value
      1.66 times greater for N-[(3)H]propylnorapomorphine than for [(11)C]raclopride at
      its highest occupancies. The results are consistent with the hypothesis that
      agonist binding is more sensitive than antagonist binding to competition from
      endogenous dopamine. Therefore, dopamine agonist ligands may be superior to
      benzamide antagonist ligands for the estimation of dopamine receptor occupancy by
      endogenous synaptic dopamine. The analysis of the effect of dopamine occupancy on
      the inhibition of N-[(3)H]propylnorapomorphine binding indicated a limited supply
      of G protein with a maximum ternary complex fraction of 40% of maximum agonist
      binding capacity.

PMID- 11973433
TI  - Comparison of near-infrared spectroscopy and tissue p(O2) time series in patients
      after severe head injury and aneurysmal subarachnoid hemorrhage.
AB  - Monitoring of local oxygen pressure in brain white matter (tip(O2)) and of local
      hemoglobin oxygen saturation (rS(O2)) with near-infrared spectroscopy (NIRS) are
      increasingly employed techniques in neurosurgical intensive care units. Using
      frequency-based mathematical methods, the authors sought to ascertain whether
      both techniques contained similar information. Twelve patients treated in the
      intensive care unit were included (subarachnoid hemorrhage, n = 3; traumatic
      brain injury, n = 9). A tip(O2) probe and an NIRS sensor were positioned over the
      frontal lobe with the most pathologic changes on initial computed tomography
      scan. The authors calculated coherence of tip(O2) and rS(O2) ts overall density
      distribution, its distribution per data set, and its time evolution. The authors
      identified a band of significantly correlated frequencies (from 0 to 1.3 x 10(3)
      Hz) in more than 90% of the data sets for coherence and overall density
      distribution. Time evolution showed slow but marked changes of significant
      coherence. By means of spectral analysis the authors show that tip(O2) and
      rS(O2)signals contain similar information, albeit using completely different
      registration methodologies.

PMID- 11973434
TI  - Endothelial nitric oxide synthase pathophysiology after nonocclusive common
      carotid artery thrombosis in rats.
AB  - Although vascular dysregulation has been documented in patients with extracranial
      vascular disease, transient ischemic attacks, and stroke, the pathomechanisms are
      poorly understood. To model thromboembolic stroke in rats, photochemically
      induced nonocclusive common carotid artery thrombosis (CCAT) was used to generate
      a platelet thrombus in the carotid artery of anesthetized rats. After CCAT,
      platelet aggregates break off the thrombus, travel to the distal cerebral
      vasculature, damage blood vessels, and cause small infarctions. The authors
      hypothesized that deficits in the endothelial nitric oxide synthase (eNOS)
      pathway may be responsible for vascular dysfunction after embolic stroke. To
      examine the functional status of the eNOS system, they measured eNOS-dependent
      dilation after CCAT by applying acetylcholine through a cranial window over the
      middle cerebral artery. The authors also measured eNOS mRNA and protein in the
      middle cerebral artery to determine whether functional changes were caused by
      alterations in expression. eNOS-dependent dilation was reduced at 6 hours,
      elevated at 24 hours, and returned to baseline 72 hours after CCAT. Endothelial
      nitric oxide synthase mRNA increased at 2 hours and was followed by a rise in
      protein 24 hours after CCAT. Changes in the eNOS system may account for some of
      the observed vascular deficits in patients with cerebrovascular disease.

PMID- 11973435
TI  - Immunohistochemical localization of calcitonin receptor-like receptor and
      receptor activity-modifying proteins in the human cerebral vasculature.
AB  - Calcitonin gene-related peptide and adrenomedullin belong to a structurally
      related neuropeptide family and are potent vasodilators expressed in the
      trigeminovascular system. The molecular identity of receptors for these proteins
      has only recently been elucidated. Central to functional binding of these
      neuropeptides is the G-protein-coupled receptor, the calcitonin receptor-like
      receptor (CRLR), whose cell surface expression and pharmacology is determined by
      coexpression of a receptor activity-modifying protein (RAMP). CRLR combined with
      RAMP binds calcitonin gene-related peptide with high affinity, whereas CRLR
      coexpression with RAMP2 or -3 confers high-affinity binding of adrenomedullin.
      The authors investigated the expression of these receptor components in human
      cerebral vasculature to further characterize neuropeptide receptor content and
      the potential functions of these receptors. Localization has been carried out
      using specific antisera raised against immunogenic peptide sequences that were
      subsequently applied using modern immunohistochemical techniques and confocal
      microscopy. The results are the first to show the presence of these receptor
      component proteins in human middle meningeal, middle cerebral, pial, and
      superficial temporal vessels, and confirm that both calcitonin gene-related
      peptide and adrenomedullin receptors may arise from the coassembly of RAMPs with
      CRLR in these vessel types. These novel data advance the understanding of the
      molecular function of the trigeminovascular system, its potential role in
      vascular headache disorders such as migraine, and may lead to possible ways in
      which future synthetic ligands may be applied to manage these disorders.

PMID- 11973436
TI  - Hot flash trends and mechanisms.

PMID- 11973437
TI  - Replacing hormones, understanding the consequences.

PMID- 11973438
TI  - A longitudinal study of the treatment of hot flushes: the population study of
      women in Gothenburg during a quarter of a century.
AB  - OBJECTIVE: To describe the prevalence and treatment of hot flushes in
      premenopausal and postmenopausal women from the 1960s to the 1990s. DESIGN: This
      prospective study, based on a random sample of the total female population of
      430,000 in Gothenburg, Sweden, was started in 1968, with follow-ups in 1974,
      1980, and 1992. The participants were 1,462 women born in 1930, 1922, 1918, 1914,
      and 1908 (participation rate 90.1%) who were representative of women of the same
      age in the general population. For the purpose of analyzing secular trends, we
      included 122 participants who were 38 years old and 47 who were 50 years old in
      1980-1981. RESULTS: The prevalence of hot flushes increased from approximately
      11% at 38 years to a maximal prevalence of approximately 60% at 52 to 54 years of
      age, then declined successively from approximately 30% at 60 years of age to
      approximately 15% at 66 years of age, and then to approximately 9% at 72 years of
      age. The predominant type of medication being prescribed changed during the
      observation period from sedatives/anticholinergic drugs in the 1960s to hormone
      replacement therapy in the 1980s. Hormone replacement therapy was considered to
      be an effective form of treatment for hot flushes by 70% to 87% of the women.
      CONCLUSIONS: Hot flushes were a common symptom, with a maximal prevalence of 64%
      at 54 years of age. Medical consultation and treatment did not increase in 50
      year-old women from 1968-1969 to 1980-1981. Treatment changed and became more
      effective during the observation period.

PMID- 11973439
TI  - The effects of tibolone on mood and libido.
AB  - OBJECTIVE: To review published data pertaining to the effects of tibolone on
      sexual parameters, mood, and cognitive function in postmenopausal women. DESIGN:
      A review of all relevant published, peer-reviewed studies. RESULTS: Tibolone is a
      compound that can be selectively metabolized by individual tissues to its
      estrogenic, progestogenic, or androgenic metabolites and hence exhibits tissue
      specific hormonal effects. Tibolone also lowers sex hormone binding globulin,
      thus increasing free estradiol and testosterone levels. Tibolone alleviates
      climacteric vasomotor symptoms and displays a dominant progestogenic effect on
      the endometrium. Tibolone normalizes the vaginal karyopyknotic and maturation
      indexes and alleviates symptomatic atrophic vaginitis. Women treated with
      tibolone report significant reductions in vaginal dryness and dyspareunia,
      effects that may be secondary to both estrogenic and androgenic actions.
      Randomized studies indicate tibolone has positive effects on mood compared with
      placebo and alleviates several adverse mood parameters to a similar extent as
      conventional hormone replacement therapy. Improved mood is associated with
      increased plasma beta-endorphin. With respect to cognition, tibolone seems to
      improve semantic memory but does not significantly improve recognition memory.
      Tibolone is associated with improvements in sexual function that seem to be
      greater than those achieved with standard hormone replacement therapy.
      CONCLUSION: Published studies indicate beneficial effects of tibolone on both
      libido and mood, which otherwise significantly compromise physical,
      psychological, and social well-being. Hence, tibolone provides another option for
      menopausal women experiencing loss of libido as part of their symptomatology or
      who have persistent low libido despite adequate estrogen/progestin replacement
      therapy.

PMID- 11973440
TI  - Oral 17beta-estradiol (1 mg) continuously combined with dydrogesterone improves
      the serum lipid profile of postmenopausal women.
AB  - OBJECTIVE: To investigate the effects of 1 mg 17beta-estradiol continuously
      combined with 2.5, 5, 10, or 20 mg dydrogesterone on the serum lipid profile of
      postmenopausal women. DESIGN: Serum lipid profile was measured in two 1-year
      studies performed in healthy, nonhysterectomized, postmenopausal women. One study
      (n = 182) had an open design and investigated oral 17beta-estradiol 1 mg daily
      continuously combined with dydrogesterone 2.5 mg daily; the other study (n = 326)
      had a double-blind, randomized design and investigated oral 17beta-estradiol 1 mg
      daily continuously combined with dydrogesterone at doses of 5, 10, or 20 mg
      daily. RESULTS: With all four dosages of dydrogesterone, serum total and low
      density lipoprotein cholesterol were significantly reduced (-4.6% to -7.6% and 
      6.3% to -11.6%, respectively), whereas high-density lipoprotein cholesterol was
      significantly increased (+4.3% to +7.4%). Serum apolipoprotein A1 and B also
      improved significantly, reflecting the favorable changes in high-density
      lipoprotein and low-density lipoprotein cholesterol, as did lipoprotein(a).
      CONCLUSION: Oral 17beta-estradiol 1 mg daily continuously combined with
      dydrogesterone 2.5 to 20 mg daily has beneficial effects on serum lipid profile
      in postmenopausal women.

PMID- 11973442
TI  - Factors associated with endometrial bleeding in continuous hormone replacement
      therapy.
AB  - OBJECTIVE: To identify clinical and laboratory parameters associated with the
      occurrence of endometrial bleeding within the first 6 months of treatment in
      postmenopausal women taking continuous hormone replacement therapy. DESIGN: We
      performed a prospective study of 55 postmenopausal women who had amenorrhea for
      at least 12 months before baseline screening and were taking 0.625 mg conjugated
      estrogen and 5 mg medroxyprogesterone acetate daily on a continuous basis.
      Postmenopausal duration was defined as the interval, in months, between the last
      menstruation and the commencement of treatment. All subjects were instructed to
      monitor bleeding episodes in a diary and were followed up monthly for at least 12
      months. RESULTS: Thirty-four women (62%) experienced bleeding within the first 6
      months of treatment. Using a multivariate approach, a woman with a postmenopausal
      duration of 24 months or less had a relative risk of 8.2 (95% confidence limits:
      1.3, 53.1) of bleeding, as compared with those with a postmenopausal duration of
      more than 24 months. Furthermore, pretreatment endometrial thickness greater than
      5 mm (p < 0.05) and serum estradiol levels greater than 25 pg/mL (p < 0.01) were
      noted to be significantly correlated with the occurrence of bleeding in women
      with a postmenopausal duration of more than 24 months. CONCLUSIONS: Women with a
      postmenopausal duration of 24 months or less, a pretreatment endometrial
      thickness greater than 5 mm, and serum estradiol level greater than 25 pg/mL are
      at risk to have endometrial bleeding within the first 6 months of continuous
      hormone replacement therapy.

PMID- 11973441
TI  - Treatment of urogenital atrophy with low-dose estradiol: preliminary results.
AB  - OBJECTIVE: To determine the lowest dosage of vaginally administered estradiol
      (E2) that reverses signs and symptoms of urogenital atrophy but does not
      substantially increase plasma E2 levels. DESIGN: Single-blind, single-arm study
      to determine the effects of de-escalating doses of vaginal estrogen on symptoms
      of urogenital atrophy, vaginal pH, and vaginal and urethral cytology. A
      questionnaire was used to assess subjective vaginal and urethral symptoms.
      Objective measurements included vaginal and urethral cytology, pH, endometrial
      biopsy, and 24-h circulating plasma luteinizing hormone, follicle-stimulating
      hormone (FSH), E2, and estrone levels obtained in a Clinical Research Unit.
      Circulating E2 levels were assayed with an ultrasensitive yeast bioassay with a
      detection limit of 0.02 pg/mL. Measurements were obtained over a 24-h period
      after administration of vehicle alone, on day 1 after the initial vaginal E2
      dosage, after 3 weeks of daily E2 administration, and after an additional 9 weeks
      of twice weekly administration. RESULTS: From the first seven subjects studied at
      a 10-microg dose of E2, 100% responded according to predefined criteria. Vaginal
      cytology showed statistical improvement at 3 and 12 weeks. Urethral cytology was
      statistically improved after 12 weeks. Vaginal pH decreased from postmenopausal
      to premenopausal levels at both 3 and 12 weeks. Eighty-two percent of symptoms
      were cured or improved. Endometrium remained atrophic. Circulating E2 levels
      remained within the postmenopausal range of 3-10 pg/mL. CONCLUSION: A 10-microg
      dose of vaginal E2 effectively treated urogenital atrophy in seven women and did
      not cause endometrial hyperplasia or increase E2 levels.

PMID- 11973443
TI  - Safety and efficacy of a continuous once-a-week 17beta-estradiol/levonorgestrel
      transdermal system and its effects on vasomotor symptoms and endometrial safety
      in postmenopausal women: the results of two multicenter, double-blind,
      randomized, controlled trials.
AB  - OBJECTIVE: Two prospective multicenter, double-blind, randomized, controlled
      trials were conducted to examine the safety and efficacy of three once-a-week
      continuous combined 17beta-estradiol/levonorgestrel (E2/LNG) transdermal systems
      (E2 0.045 mg/day with 0.015, 0.030, and 0.040 mg/day LNG) for the treatment of
      vasomotor symptoms and prevention of estrogen-induced endometrial hyperplasia in
      healthy, postmenopausal women. DESIGN: In study 1, performed in 293
      hysterectomized and nonhysterectomized women with moderate to severe hot flushes,
      transdermal E2/LNG (E2 0.045 mg/day with 0.030 and 0.040 mg/day LNG) was compared
      with placebo for three 28-day treatment cycles. The frequency and severity of hot
      flushes were recorded daily. In study 2, performed in 845 women with intact
      uteri, transdermal E2/LNG (E2 0.045 mg/day with 0.015, 0.030, and 0.040 mg/day
      LNG) was compared with transdermal E2 0.045 mg/day monotherapy for thirteen 28
      day treatment cycles. Women with endometrial tissue sufficient for evaluation
      underwent endometrial biopsy assessment at the end of cycle 13. Bleeding patterns
      were assessed throughout the study, and the Women's Health Questionnaire was used
      to assess well-being. RESULTS: In study 1, transdermal E2/LNG (E2 0.045 mg/day
      with 0.030 and 0.040 mg/day LNG) significantly decreased the number and severity
      of hot flushes when compared with placebo. Symptom relief was seen as early as 2
      weeks posttreatment. Similarly, in study 2, all three doses of transdermal E2/LNG
      and E2 controlled hot flushes with no differences between groups. In study 2, no
      women receiving transdermal E2/LNG developed endometrial hyperplasia compared
      with 19 (12.8%) who received transdermal E2 0.045 mg/day (p < 0.001 for each
      dose). Significant improvements from baseline in scores on the Women's Health
      Questionnaire for vasomotor symptoms, sleep problems, sexual function, cognitive
      difficulties, and total score were noted at all or most time points with both
      transdermal E2/LNG and E2. Application-site reactions, vaginal hemorrhage, and
      breast pain were the most common adverse events reported with transdermal E2/LNG.
      The proportion of women with amenorrhea increased over time in all treatment
      groups in study 2. CONCLUSIONS: All three doses of this once-a-week combined
      E2/LNG transdermal system rapidly and effectively control vasomotor symptoms in
      postmenopausal women while protecting against endometrial hyperplasia.
      Amelioration of vasomotor symptoms also is accompanied by improvements in aspects
      of subjective well-being. Once-a-week transdermal E2/LNG, therefore, offers an
      effective and convenient formulation, the dosing of which can be individualized
      according to the needs of each patient.

PMID- 11973445
TI  - Female sex hormones and venous distensibility.

PMID- 11973444
TI  - Maximizing health in menopausal women with disabilities.
AB  - There are nearly 30 million women with disabilities in the United States. Of
      these, more than 16 million are over the age of 50. Years ago, women with
      disabilities did not commonly live to the age of menopause, and, if they did,
      they reached this stage of life in a very debilitated condition. Now, women with
      disabilities are entering their mature years as active members of society who can
      look forward to productive futures. Because the health needs of women with
      disabilities might differ from those of other women, special attention should be
      focused on how physiological changes of perimenopausal and menopausal states
      affect this population. In addition to functional changes that might affect
      menopausal women with disabilities, basic health maintenance issues may be
      adversely affected by environmental factors. Physical barriers can influence
      compliance with preventive health screening that is essential in aging
      populations. Treatment options might need to be tailored to the individual. The
      disabling condition itself may progress, resulting in secondary conditions
      requiring creative interventions. A comprehensive evaluation and the development
      of a suitable management plan, which takes into account the multifactorial nature
      of aging as a disabled woman, are essential in delivering optimal care to this
      population.

PMID- 11973446
TI  - D2 receptor blockade in the dorsal raphe increases quinpirole-induced locomotor
      excitation.
AB  - The D2/D3 dopamine receptor agonist quinpirole (QNP) produces biphasic effects on
      locomotion and can induce oral behaviour. To determine whether or not these
      behaviours result from actions of QNP at D2 receptors located in the dorsal
      raphe, nucleus (DRN), rats were pretreated intra-DRN with the selective dopamine
      D2 receptor antagonist, raclopride (0, 1 or 2 microg) prior to an acute
      peripheral injection of QNP (0 or 0.5 mg/kg, s.c.). Intra-DRN raclopride did not
      affect QNP-induced oral activity or QNP-induced locomotor inhibition. However,
      the high dose of raclopride potentiated QNP-induced locomotor excitation. These
      data suggest that D2 receptor activation in the DRN suppresses QNP-induced
      locomotor excitation, an effect that may be related to D2 receptor-mediated
      alterations in serotonin transmission.

PMID- 11973447
TI  - Cannabidiol, a non-psychoactive component of cannabis and its synthetic
      dimethylheptyl homolog suppress nausea in an experimental model with rats.
AB  - Rats display conditioned rejection reactions during an oral infusion of a flavor
      previously paired with an emetic drug; considerable evidence indicates that these
      rejection reactions reflect nausea. Here we report that cannabidiol, a major non
      psychoactive cannabinoid found in marijuana and its synthetic dimethylheptyl
      homolog interfere with nausea elicited by lithium chloride and with conditioned
      nausea elicited by a flavor paired with lithium chloride. These results suggest
      that cannabinoids without psychoactive side-effects may have therapeutic value in
      the treatment of chemotherapy-induced nausea.

PMID- 11973448
TI  - Braille character discrimination in blindfolded human subjects.
AB  - Visual deprivation may lead to enhanced performance in other sensory modalities.
      Whether this is the case in the tactile modality is controversial and may depend
      upon specific training and experience. We compared the performance of sighted
      subjects on a Braille character discrimination task to that of normal individuals
      blindfolded for a period of five days. Some participants in each group
      (blindfolded and sighted) received intensive Braille training to offset the
      effects of experience. Blindfolded subjects performed better than sighted
      subjects in the Braille discrimination task, irrespective of tactile training.
      For the left index finger, which had not been used in the formal Braille classes,
      blindfolding had no effect on performance while subjects who underwent tactile
      training outperformed non-stimulated participants. These results suggest that
      visual deprivation speeds up Braille learning and may be associated with
      behaviorally relevant neuroplastic changes.

PMID- 11973449
TI  - Neurological signs in parents of schizophrenic patients.
AB  - The importance of neurological abnormalities in relatives of schizophrenic
      patients is not completely clear and has been questioned. The hypothesis that
      neurological abnormalities are trait markers for a vulnerability to develop
      schizophrenia was tested in 32 parents of patients with schizophrenia and 34
      healthy controls. A comprehensive and standardized neurological assessment
      battery was used. The examiners were blind as to whether they tested a parent of
      a patient or a healthy control. Four function domains were investigated; higher
      cerebral functions, cranial nerve functions, general motor functions and gait.
      There were no significant differences between parents of patients and healthy
      controls on any of the neurological function domains, or on the total number of
      neurological abnormalities. No difference was found between parents with a
      positive family history of schizophrenia spectrum disorders, parents with a
      negative family history and controls. Results suggest that the neurological
      functions investigated are not related to a genetic liability to develop
      schizophrenia.

PMID- 11973450
TI  - Assessing cerebral representations of short and long vowel categories by NIRS.
AB  - The present study examined cerebral representations of Japanese long and short
      vowel categories with near-infrared spectroscopy (NIRS) by measuring the
      hemodynamic changes. Results showed that NIRS could capture phoneme-specific
      information. The left side of the auditory area showed large hemodynamic changes
      only for contrasting stimuli between which the phonemic boundary was estimated,
      but not for stimuli differing by an equal duration but belonging to the same
      phoneme category. Left dominance in phoneme processing was also confirmed for the
      across-category stimuli. These findings indicate that the Japanese vowel contrast
      based only on duration differences is dealt with in the same language-dominant
      hemisphere as other spectrally varying phonemic categories, and that the cortical
      activities related to its processing can be detected with NIRS.

PMID- 11973451
TI  - Ionic basis of the resting membrane potential in cultured rat sympathetic
      neurons.
AB  - The conductances which determine the resting membrane potential of rat superior
      cervical ganglia (SCG) neurons were investigated using perforated voltage- and
      current-clamp whole-cell techniques. The resting potential of SCG cells varied
      from -47 to -80 mV (-58.3 +/- 0.8 mV, n = 55). Blockade of M and h currents
      induced a depolarisation (7.4 +/- 0.7 mV, n = 22) and a hyperpolarisation (7.2 +/
      0.7 mV, n = 20) respectively; however, no correlation between the amplitude of
      these currents and the resting potential was found. The inhibition of the Na/K
      pump also induced membrane depolarisation (3.2 +/- 0.2 mV, n = 8). Inhibition of
      voltage-gated currents unmasked a voltage-independent resting conductance
      reversing at -50 mV. The reversal potential of the voltage-independent
      conductance, which included the electrogenic contribution of the Na/K pump, was
      strongly correlated with the resting potential (R = 0.87, p < 0.0001, n = 30).
      Ionic substitution experiments confirmed the existence of a voltage-independent
      conductance (leakage) with four components, a main potassium conductance, two
      minor sodium and chloride conductances and a small contribution of the Na/K pump.
      It is concluded that the resting potential of SCG cells strongly depends on the
      reversal potential of the voltage-independent conductance, with voltage-activated
      M and h currents playing a prominent stabilising role.

PMID- 11973452
TI  - Anandamide-induced neuroblastoma cell rounding via the CB1 cannabinoid receptors.
AB  - The CB1 cannabinoid receptor has been shown to couple with pertussis toxin (PTX)
      sensitive Gi/o proteins and inhibit adenylyl cyclase. However, in certain
      conditions, CB1 mediates adenylyl cyclase activation, possibly through Gs-type G
      proteins. In rat B103 neuroblastoma cells in which CBI gene was endogenously
      expressed, anandamide inhibited forskolin-induced cAMP accumulation via PTX
      sensitive pathways. When CB1 was heterologously over-expressed using a retroviral
      transfer, high concentrations of anandamide increased forskolin-induced cAMP
      accumulation, and this effect was more prominent when cells were pretreated with
      PTX. In CB1-over-expressing B103 cells, anandamide induced cell rounding via a
      PTX-insensitive/Rho kinase inhibitor-sensitive pathway. These results suggest
      that the CB1 receptor could couple with G proteins that activate Rho (possibly
      G12/13) as well as Gi/o and Gs.

PMID- 11973453
TI  - Enhancing tactile sensation in older adults with electrical noise stimulation.
AB  - Older adults often suffer from diminished somatosensation stemming from age
      related neuropathy. Recently, localized low-level electrical noise stimulation
      was shown to enhance tactile sensitivity in healthy young subjects. Here, we
      hypothesized that fine-touch sensitivity in older adults can be similarly
      improved. Semmes-Weinstein monofilaments were used to evaluate fine-touch
      sensitivity on the first metatarsal phalangeal joint with four electrical
      stimulus conditions and a null (no-noise) condition in nine healthy elderly
      subjects. Electrical noise stimulation resulted in a statistically significant
      increase in the number of detections below the null-condition detection
      threshold, for five of the nine subjects, as well as across the entire
      population. This work suggests that electrical noise-based techniques may enable
      people to overcome functional difficulties due to age-related sensory loss.

PMID- 11973454
TI  - Intraneuronal advanced glycation endproducts in presenilin-1 Alzheimer's disease.
AB  - The most frequently mutated gene resulting in dominantly inherited Alzheimer's
      disease is presenilin-1. We have used antibodies against advanced glycation
      endproducts (AGE) in brain tissue sections of four patients with three different
      presenilin I mutations. Accumulation of intracellular AGE was observed in 75-95%
      of pyramidal neurons in patients with presenilin-1 mutations, far exceeding the
      percentage of presenilin-1-, tau- or ubiquitin-positive neurons. This high level
      of AGE-modified proteins in vulnerable neurons is most likely explained by higher
      levels of their precursors (reactive (di)carbonyl products) or a slower turnover
      of the participating proteins. These conditions of carbonyl stress may contribute
      to increased neuronal dysfunction and vulnerability leading to the early disease
      onset.

PMID- 11973455
TI  - Exploring imagined movements in patients with schizophrenia.
AB  - Patients with schizophrenia demonstrate impairments indicative of an inability to
      accurately monitor internally generated images. Motor imagery measures the
      ability to generate internal images of intended but not executed motor movements.
      Ten patients with schizophrenia completed actual and imagined versions of a
      pointing task with a well defined speed-accuracy trade-off function. For
      controls, movement time increases as target size decreases for both actual and
      imagined movements. Despite showing the expected speed-accuracy trade-off for
      actual movements, the imagined movements of schizophrenics showed no reliable
      relationship to target size. This was true for each patient and appeared to be
      independent of symptom profile. These results suggest that patients with
      schizophrenia are unable to generate accurate internal images of their own motor
      movements.

PMID- 11973456
TI  - Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients.
AB  - By comparing the CSF proteome between Alzheimer disease (AD) patients and
      controls it may be possible to identify proteins that play a role in the disease
      process and thus to study the pathogenesis of AD. We used mini-gel technology in
      a two-dimensional electrophoresis procedure, sensitive SYPRO Ruby staining and
      mass spectrometry for clinical screening of disease-influenced CSF proteins in 15
      AD patients and 12 controls. The levels of six proteins and their isoforms,
      including proapolipoprotein, apolipoprotein E, beta-2 microglobulin, retinol
      binding protein, transthyretin, and ubiquitin, were significantly altered in CSF
      of AD patients. The most prominently altered proteins were the apolipoproteins,
      especially proapolipoprotein.

PMID- 11973457
TI  - Dyslexia: verbal impairments in the absence of magnocellular impairments.
AB  - Sensitivity to dynamic visual and auditory stimuli was assessed in dyslexic
      children (Grade 7) who at school entrance had suffered from the well-established
      double-deficit of impaired phonological sensitivity and deficient rapid naming
      performance. A visual magnocellular deficit was assessed by the coherent motion
      detection task of the Oxford group. An auditory magnocellular deficit was
      assessed by the illusory sound movement perception task of Hari and Kiesila. On
      both tasks our dyslexic subjects' performance was similar or even better than the
      performance of normally reading controls. Differences in the inclusion of ADHD
      cases in dyslexic samples is discussed as a potential explanation of differences
      in results.

PMID- 11973459
TI  - Axonal lesions and PDGF-enhanced remyelination in the rat corpus callosum after
      lysolecithin demyelination.
AB  - In multiple sclerosis (MS), demyelination is often accompanied by axonal lesions,
      which largely account for patient disability. We therefore studied the
      consequences of demyelination induced by lysophosphatidylcholine (LPC) on the
      axonal cytoskeleton, particularly neurofilaments (NF) and tubulin, in the adult
      rat corpus callosum. Immunocytochemistry showed that NF immunolabelled fibres
      decreased by 49% in the LPC injured area at day 15. Since it has been previously
      demonstrated that PDGF improves remyelination, we performed a comparative study
      between LPC controls and PDGF-treated (1 microg) animals. In these later animals,
      immunolabelling for NFL and NFM (NFH subunit excepted) was increased by 142 and
      63%, respectively, indicating reduction of axonal abnormalities. These results
      extend the potential therapeutic role of PDGF in MS.

PMID- 11973458
TI  - Nerve growth factor promotes olfactory axonal elongation.
AB  - An explant culture system was used to test the effect of nerve growth factor
      (NGF) on olfactory axonal elongation. Statistical analysis showed that
      exogenously applied NGF (50 ng/ml) significantly enhanced olfactory neurite
      elongation from E14 rat olfactory epithelial explants (p = 0.025). Immunostaining
      showed that the neurites expressed active TrkA receptors and that S-100-positive
      ensheathing cells were also present. In a separate experiment, immunoassay
      confirmed that following a growth period of 72 h, E14 presumptive olfactory bulb
      expressed and secreted NGF into the culture medium. The results indicate that
      during ontogeny, the olfactory bulb secretes NGF which binds to olfactory axons
      and facilitates their elongation.

PMID- 11973460
TI  - Visuospatial updating of reaching targets in near and far space.
AB  - The brain constructs multiple representations of near and far space but it is
      unclear which spatial mechanism guides reaching across eye movements in near
      space. Retinocentric reaching representations are known to exist in parietal
      cortex, but must be updated during eye movements, in order to remain accurate. In
      contrast, non-retinal (e.g. muscle-centered) reaching plans in motor cortex do
      not require updating, and so may provide a more stable encoding mechanism. To
      test between these, we employed a behavioral test. Subjects briefly foveated a
      target (located at various depths in near and far space) looked peripherally,
      then reached toward its remembered location. Surprisingly, subjects did not use
      the stable non-retinal reaching plan (compared to controls without eye
      movements). Instead, the intervening eye movements induced a systematic pattern
      of reaching errors for targets at all depths consistent with updating in a
      retinal frame. We conclude that a common eye-centered updating mechanism prevails
      in programming arm movements in both near and far space.

PMID- 11973461
TI  - Modification of a functional motor task by non-consciously perceived sensory
      stimuli.
AB  - In recent years it has been suggested that processing of visual information is
      divided between a ventral stream, responsible for object recognition and
      conscious processing of object properties, and a dorsal stream mediating
      automatic integration of visual information into a motor task. We used
      metacontrast masking to prevent conscious perception of visual cues concerning
      the load of an object to be lifted in a precision grip. It was found that when
      such non-consciously perceived cues warned of a load change, they allowed the
      subjects to produce the grip force profile appropriate to the new load. It is
      concluded that non-consciously perceived visual information can be utilised to
      adapt a functional motor task to actual conditions.

PMID- 11973462
TI  - Impairment of mitochondrial metabolism differentially affects striatal neuronal
      subtypes.
AB  - Electrophysiological and microfluorometric measurements were combined to analyse
      the responses of rat striatal medium spiny (MS) and large aspiny (LA)
      interneurons to the mitochondrial uncoupler carbonyl cyanide p
      trifluoromethoxyphenylidrazone (FCCP). FCCP produced a membrane depolarisation
      coupled to an irreversible increase in intracellular calcium [Ca2+]i in MS.
      Conversely, LA interneurons hyperpolarised and a moderate [Ca2+]i rise was
      observed. Cyclosporin A, inhibitor of the mitochondrial membrane transition pore,
      prevented the FCCP-induced changes in LA interneurons, whereas only a partial
      reduction was observed in MS cells. The present results indicate that
      mitochondrial Ca2+ released into the cytosol may contribute to the selective
      vulnerability to metabolic impairment in striatal neuronal subtypes.

PMID- 11973463
TI  - Modulation of proorphaninFQ/N gene expression by morphine in the rat
      mesocorticolimbic system.
AB  - We studied the effects of acute and chronic morphine treatment on proorphaninFQ/N
      (proOFQ/N) gene expression in the mesocorticolimbic system, known to be a reward
      relevant area, of the rat CNS. Northern blot analysis revealed that a single
      injection of morphine 10 mg/kg i.p. increased proOFQ/N mRNA levels in nucleus
      accumbens, temporo-parietal cortex and in striatum. The chronic administration of
      the opiate caused a significant increase of proOFQ/N mRNA levels in the ventral
      tegmental area and a decrease in the striatum and in the nucleus accumbens. No
      changes were observed in the prefrontal cortex. These data indicate for the first
      time that morphine alters proOFQ/N gene expression in mesocorticolimbic areas,
      supporting the direct interaction between the opioid and OFQ/N systems and the
      OFQ/N involvement in morphine-rewarding mechanisms.

PMID- 11973464
TI  - The origin of catecholaminergic inputs to the song control nucleus RA in
      canaries.
AB  - Song control nuclei in oscines receive dense catecholaminergic inputs but their
      anatomical origin is poorly understood. We analyzed catecholaminergic inputs to
      the nucleus robustus archistriatalis (RA) in canaries by retrograde tract-tracing
      combined with immunocytochemistry for tyrosine hydroxylase. In both sexes,
      dopaminergic inputs to RA come mostly from the A1 1 (mesencephalic central gray)
      and A10 (area ventralis of Tsai) cell groups but the locus coeruleus and
      subcoeruleus (A6) also send noradrenergic projections to RA. No input originates
      in the hypothalamic and in the A5 to A1 catecholaminergic groups. These findings
      and previous work on the high vocal center (HVc) indicate that the two major
      nuclei of the motor pathway controlling song production (RA and HVc) receive
      catecholaminergic inputs of similar origins.

PMID- 11973465
TI  - A temporal/nasal asymmetry for blindsight in a localisation task: evidence for
      extrageniculate mediation.
AB  - Some patients with hemianopia due to striate cortex lesions show above chance
      ability in reporting visual stimuli presented in the blind visual field, a
      phenomenon commonly known as blindsight. Here we report a patient with a dense
      right hemianopia whose blindsight shows a temporal/nasal asymmetry. MP was tested
      in a two-alternative forced-choice localisation task, with either the right eye
      or the left eye patched in separate blocks. When targets appeared in the
      contralesional temporal hemifield, MP's localisation performance was extremely
      accurate, whilst she performed at chance with targets in the contralesional nasal
      hemifield. This is the first demonstration of a temporal/nasal asymmetry for
      blindsight in a forced-choice paradigm, and is consistent with blindsight in MP's
      hemianopic field being mediated by a subcortical, extrageniculate route.

PMID- 11973466
TI  - Anterograde axonal transport of internalized GDNF in sensory and motor neurons.
AB  - Endogenous glial cell line-derived neurotrophic factor (GDNF) has been shown to
      be anterogradely transported in sensory and motor neurons which do not express
      detectable levels of GDNF mRNA. The source of the anterograde axonal GDNF in
      these neurons has remained unclear. Here we show that radiolabeled GDNF is
      internalized by dorsal root ganglion (DRG) and hypoglossal motor neurons at their
      cell bodies and/or their dendrites and that a mechanism exists to transport the
      internalized GDNF anterogradely in their axons. Since adjacent glial cells
      express GDNF mRNA, these data support the concept that Schwann cell- or
      oligodendrocyte-derived GDNF is taken up by DRG and motor neurons, respectively,
      and transported anterogradely along the axons for release from terminals,
      resulting in neuronal transcytosis.

PMID- 11973467
TI  - A prospective study of motor recovery following multiple subpial transections.
AB  - A prospective study of motor recovery was undertaken in a patient scheduled to
      undergo multiple subpial transections (MST) of right sensorimotor cortex. Pre
      transection, functional MRI (fMRI) and cortical stimulation mapping confirmed
      left hand motor control within right primary motor cortex. Immediately post
      transection, behavioral testing demonstrated preserved strength bilaterally but
      decreased dexterity in the left hand. Seven weeks post-transection, dexterity
      returned to normal and left hand finger tapping corresponded with multiple
      bilateral foci of fMRI activation. At 16 weeks, fMRI activation returned to pre
      transection levels. These data indicate that cortical injury due to MST resulted
      in the temporary recruitment of distant cortical sites which presumably subserved
      normal motor function during recovery.

PMID- 11973468
TI  - Stimulus-specific induction of an Egr-1 transgene in rat brain.
AB  - Regulated expression of Egr-1 (Zif268/NGFIA) in a variety of brain networks
      suggests a diversity of roles in neuronal plasticity. Here, we aimed to determine
      whether an egr-1 transgene would mediate transcriptional responses to different
      pharmacological and physiological stimuli in the brain of transgenic rats.
      Constitutive transgene expression was observed in the cortex, CA1 hippocampal
      area and pituitary, recapitulating expression of egr-1. Transgene induction was
      stimulus-specific. Metrazole induced widespread expression in the dentate gyrus,
      CA2 and CA3 areas, amygdala, and ventromedial nucleus. In contrast, induction
      following a light stimulus was restricted to the hypothalamic suprachiasmatic and
      periventricular nuclei. Our studies have provided novel insights into the
      differential regulation of egr-1, and facilitated approaches to the genetic
      manipulation of Egr-1-regulated neuronal systems.

PMID- 11973469
TI  - Responses of hepatic and celiac vagal afferents to intraportal mercaptoacetate in
      rats fed a high-fat or low-fat diet.
AB  - Responses of either hepatic or celiac vagal afferents to intraportal hepatic vein
      administration of 2-mercaptoacetate (MA) were examined in rats maintained on
      either a high-fat or low-fat diet. Afferent activity in both hepatic and celiac
      vagal afferents significantly increased after administration of MA, but the
      magnitude of these increases did not differ as a function of either diet.
      Responses of hepatic vagal afferents were highly variable across individual rats,
      whereas those of celiac vagal afferents were remarkably consistent across
      individual rats. These data suggest that MA-induced enhanced feeding in rats
      given a fat-enriched diet does not depend on a stronger hepatic and/or celiac
      vagal afferent response than that of rats given a low-fat diet.

PMID- 11973470
TI  - Attentional switching-related human EEG alpha oscillations.
AB  - Alpha oscillations during cognitive performance have mostly been studied in
      memory and/or basic attention tasks. This study investigates task-related alpha
      power desynchronization during an attentional switching task requiring higher
      executive attentional control. Low 8-10 Hz and high 10-12 Hz alpha power
      responses are studied in good versus poor performers based upon normative data.
      Accurate, fast and stable performers showed significant task-related
      desynchronization in the 8-10 Hz range during attentional switching, whereas
      inaccurate performers hypersynchronized in the 10-12 Hz range, and slow and
      unstable performers did not demonstrate significant alpha reactivity. These
      preliminary findings indicate, in agreement with previous research, functional
      differences in these narrow frequency bands. The 8-10 Hz power decrease is likely
      to be related to phasic arousal or alertness, whereas the 10-12 Hz power increase
      appears to be associated with inaccurate attentional switching.

PMID- 11973472
TI  - Attending to the thalamus: inhibition of return and nasal-temporal asymmetry in
      the pulvinar.
AB  - Inhibition of return (IOR) is a mechanism whereby the attentional system favors
      novel locations by inhibiting already scanned ones. An important question is what
      the neural structures are involved. Recently, we studied a patient with damage to
      the superior colliculus (SC) and concluded that the SC generates IOR. However, it
      is possible that IOR is generated beyond the colliculus, for example, by the
      pulvinar. In this paper we tested three patients with unilateral damage to the
      pulvinar and demonstrated that the pulvinar is not necessary for IOR generation,
      providing additional support to the suggestion that the SC generates IOR. In
      addition, since we used monocular presentation, we were able to furnish
      behavioral evidence for nasal-temporal asymmetrical representation of visual
      input in the pulvinar.

PMID- 11973473
TI  - Increased somatosensory neuromagnetic fields ipsilateral to lesions in
      neurosurgical patients.
AB  - This study is aimed to determine whether the presence of a tumor in close
      proximity to the somatosensory cortex of the post-central gyrus affects the
      response evoked from such an area by painless tactile stimulation, recorded by
      MEG. The main finding of this study is that somatosensory evoked field strengths
      from cortex ipsilateral to and abutting an intracranial tumor are significantly
      elevated compared with either contralateral control fields, or with somatosensory
      evoked fields elicited from cortex ipsilateral to, but distant from tumors
      (typically involving language areas, such as inferior frontal lobe). Biophysical
      and biochemical explanations implicate hyperactivity of cortical neurons close to
      the tumor, suggesting a possible role of MEG as a measure of tumor infiltration.

PMID- 11973471
TI  - Induction mechanisms for L-LTP at thalamic input synapses to the lateral
      amygdala: requirement of mGluR5 activation.
AB  - L-LTP (late-phase long-term potentiation) at thalamo-amygdala synapses is thought
      to be critical for auditory fear conditioning, but it has not been clear what
      kinds of surface receptors and channels are involved in the induction phase of
      the L-LTP. Here we report that the NMDA receptor antagonist D-AP5 (50 microM),
      the L-type calcium channel antagonist nifedipine (30 microM) and the metabotropic
      glutamate receptor 5 antagonist MPEP (10 microM) prevented L-LTP induction when
      each antagonist was separately applied at saturating concentrations before and
      during repeated tetanus. By contrast, the mGluR1 antagonist CPCCOEt (80 microM)
      failed to show any effects on L-LTP induction. Neither D-AP5 nor MPEP produced
      any significant effects on potentiated synaptic responses when applied after L
      LTP had been established. Thus, our data suggest that NMDA receptors, L-type
      calcium channels and mGluR5 are involved in L-LTP induction in the thalamo
      amygdala pathway.

PMID- 11973474
TI  - Altered functional MRI responses in Huntington's disease.
AB  - This study examined the effects of Huntington's disease (HD) on neural activity
      during performance of the Porteus maze task. fMRI data were acquired from three
      HD patients and three controls. Reduced fMRI signal was observed in the patients
      relative to the controls in occipital, parietal and somato-motor cortex and in
      the caudate, while increased signal was found in HD in the left postcentral and
      right middle frontal gyri. The altered fMRI responses in HD patients may result
      from neural, metabolic, neurovascular coupling and/or hemodynamic differences
      associated with this disorder.

PMID- 11973475
TI  - Biphasic developmental changes in Ca2+/calmodulin-dependent proteins in R6/2
      Huntington's disease mice.
AB  - Widespread disturbances in calcium-dependent proteins are reported both in humans
      with advanced Huntington's disease (HD) and in symptomatic HD transgenic mice.
      Using a HD mouse model transgenic for exon 1 of the abnormal gene (e.g. the Bates
      R6/2 mouse), we found increased expression of calmodulin kinase IV and neuronal
      nitric oxide synthase (NOS) in 3-week-old presymptomatic HD mice striatum and
      cortex. Conversely, reduced expression was found at 6 weeks (early symptom onset)
      and 11 weeks (advanced disease) of age. The changes in protein expression may
      have a broad impact on the HD striatum. Calmodulin kinase IV directly regulates
      the activation of the transcription factors CREB (cyclic AMP response element
      binding protein) and CREM (cyclic AMP response element modulator) and, as well,
      modulates the activity of neuronal NOS. In homeostasis, nitric oxide is involved
      in long-term potentiation, neurotransmission, endocrine regulation and cerebral
      blood flow regulation, among others, while under pathological conditions nitric
      oxide combines with superoxide to produce the potent neurotoxin peroxynitrite.
      The current findings suggest that mutant HD protein may alter these processes by
      disturbing the regulation of calmodulin kinase IV and neuronal NOS expression
      across the lifespan of the HD mouse.

PMID- 11973476
TI  - Cell-type specific alterations of cortical interneurons in schizophrenic
      patients.
AB  - In the human brain, cortical GABAergic interneurons represent an important
      population of local circuit neurons responsible for the intrinsic modulation of
      neuronal information and have been supposed to be involved in the pathophysiology
      of schizophrenia. We conducted a quantitative study on the differentiated three
      dimensional morphological structure of two types of parvalbumin-immunoreactive
      interneurons in the anterior cingulate cortex (ACC) of schizophrenic patients
      versus controls. While type A interneurons ('small bipolar cells') showed a
      significant reduction of their soma size in schizophrenics, type B interneurons
      ('small multipolar cells') of schizophrenic patients exhibited a marked decrease
      in the extent of their dendritic system. These results further support the
      assumption of a considerable significance of the ACC, an important limbic relay
      centre, for the etiopathogenesis of schizophrenic psychoses.

PMID- 11973477
TI  - Alternative transcripts of presenilin-1 associated with frontotemporal dementia.
AB  - We have analyzed the expression of Alzheimer's disease-associated presenilin 1
      (PS1) in various neurodegenerative disorders. Western blotting identified PS1 N-
      and C-terminal fragments similarly in the cortex of controls, Parkinson,
      Huntington and schizophrenia subjects. Additional PS1 immunoreactive species of
      42 and 46 kDa were present in six out of seven cases of sporadic frontotemporal
      dementia (FTD) and these were particularly prominent in two cases. RT-PCR
      analysis using nested primers showed the presence of PS1 gene products with
      deletions within the exon 4-8 region. Our results suggest that alternative
      transcription of PS1 may be associated with FTD.

PMID- 11973478
TI  - NO synthase inhibitors attenuate locus coeruleus catecholamine metabolism and
      behavior induced by morphine withdrawal.
AB  - The effects of nitric oxide synthase (NOS) inhibitors were examined
      simultaneously on the behavior and on the catecholaminergic metabolism in the
      locus coeruleus (LC) during morphine withdrawal using microdialysis in freely
      moving rats. Morphine withdrawal was precipitated by naltrexone administration to
      morphine-treated rats. Acute pretreatment of rats with NOmicron-nitro-L-arginine
      p-nitroanilide (L-NAPNA) or 7-nitroindazole (7-NI) before naltrexone challenge
      attenuated the behavioral expression of morphine withdrawal and strongly reduced
      the withdrawal-induced increase in 3,4-dihydroxyphenylacetic acid (DOPAC) in the
      LC. The two NOS inhibitors also decreased DOPAC in absence of naltrexone
      challenge. These results suggest a role for NO in the expression of morphine
      withdrawal syndrome that may be mediated, at least in part, by LC noradrenergic
      neurons.

PMID- 11973479
TI  - Delta- and kappa-opioid receptors in the caudal midline medulla mediate
      haemorrhage-evoked hypotension.
AB  - In mammals blood loss can trigger, shock, an abrupt, life-threatening hypotension
      and bradycardia. In the halothane-anaesthetised rat this response is blocked by
      inactivation of a discrete, vasodepressor area in the caudal midline medulla
      (CMM). Haemorrhagic shock is blocked also by systemic or ventricular injections
      of the opioid antagonist, naloxone. This study investigated, in the halothane
      anaesthetised rat, the contribution of delta-, kappa- and mu-opioid receptors in
      the CMM vasodepressor region to haemorrhage-evoked shock (i.e. hypotension and
      bradycardia) and its recovery. It was found that microinjections into the CMM of
      the delta-opioid receptor antagonist, naltrindole delayed and attenuated the
      hypotension and bradycardia evoked by haemorrhage, but did not promote
      recompensation. In contrast, CMM microinjections of the kappa-opioid receptor
      antagonist, nor-binaltorphamine, although it did not alter haemorrhage-evoked
      hypotension and bradycardia, did lead to a rapid restoration of AP, but not HR.
      CMM microinjections of the mu-opioid receptor antagonist, CTAP had no effect on
      haemorrhage-evoked shock or recompensation. These data indicate that delta- and
      kappa- (but not mu-) opioid receptor-mediated events within the CMM contribute to
      the hypotension and bradycardia evoked by haemorrhage and the effectiveness of
      naloxone in reversing shock.

PMID- 11973482
TI  - Current status and future of continuous radionuclide left ventricular function
      monitoring.

PMID- 11973480
TI  - CNTF is specifically expressed in developing rat pineal gland and eyes.
AB  - Ciliary neurotrophic factor (CNTF) attracts considerable attention because it
      supports survival and differentiation of various types of neurons and glial cells
      in vitro. Although CNTF functions as a moderate neurotrophic factor in mature
      motor neurons, its role in embryonic development remains unknown. Here, we found
      a specific CNTF expression in the rat pineal gland and eyes during embryonic
      development. In vitro, neonatal rat pineal extract including CNTF supported the
      survival of neonatal sympathetic neurons, which innervate pineal glands
      immediately after birth.

PMID- 11973483
TI  - Differences in resting state regional cerebral blood flow assessed with 99mTc
      HMPAO SPECT and brain atlas matching between depressed patients with and without
      tinnitus.
AB  - An increased occurrence of major depressive disorder has been reported in
      tinnitus patients, and of tinnitus in depressive patients. Involvement of several
      Brodmann areas (BAs) has been reported in tinnitus perception. The aim of this
      study was to assess the regional cerebral blood flow (rCBF) changes in depressed
      patients with and without tinnitus. The rCBF distribution at rest was compared
      among 45 patients with a lifetime prevalence of major depressive disorder, of
      whom 27 had severe tinnitus, and 26 normal healthy subjects. 99mTc
      hexamethylenepropylene amine oxime (99mTc-HMPAO) single photon emission computed
      tomography (SPECT), using a three-headed gamma camera, was performed and the
      uptake in 34 functional sub-volumes of the brain bilaterally was assessed by a
      computerized brain atlas. Decreased rCBF in right frontal lobe BA 45 (P<0.05),
      the left parietal lobe BA 39 (P<0.00) and the left visual association cortex BA
      18 (P<0.05) was found in tinnitus patients compared with non-tinnitus patients.
      The proportion of tinnitus patients with pronounced rCBF alterations in one or
      more of the temporal lobe BAs 41+21+22 was increased compared to gender matched
      controls (P<0.00) and patients without tinnitus (P<0.05). Positive correlations
      were found between trait anxiety scales from the Karolinska Scales of Personality
      and rCBF in tinnitus patients only in three limbic BAs (P<0.01), and inverse
      correlations in non-tinnitus patients only in five BAs subserving auditory
      perception and processing (P<0.05). rCBF differences between healthy controls and
      depressed patients with and without tinnitus were found in this study. The rCBF
      alterations were distributed in the cortex and were particularly specific in the
      auditory cortex. These findings suggest that taking audiological symptoms into
      account may yield more consistent results between rCBF studies of depression.

PMID- 11973484
TI  - Impaired lung epithelial permeability in hepatitis C virus antibody positive
      patients detected by 99mTc-DTPA aerosol scintigraphy.
AB  - Chronic hepatitis C virus (HCV) infection has been recently identified as an
      aetiological agent in idiopathic pulmonary fibrosis. The present study was
      designed to determine the pulmonary clearance rate of 99mTc
      diethylenetriaminepentaacetic acid (99mTc-DTPA) in asymptomatic HCV antibody
      positive (HCV Ab+) patients and the role of 99mTc-DTPA aerosol scintigraphy in
      the early detection of lung involvement. Twenty-six non-smoker HCV Ab+ and HCV
      RNA (+) patients (20 female, six male; aged 43+/-11 years), with no clinical
      pulmonary symptoms, and normal radiological findings, were studied. Thirty-one
      healthy non-smoker volunteers (24 female, seven male; aged 40+/-10 years) were
      taken as a control group. 99mTc-DTPA aerosol inhalation scintigraphy and
      pulmonary function tests were performed in all patients and in controls. On the
      basis of the scintigrams the percentage decline in activity per minute (Kep) was
      evaluated, which represented an accurate parameter of lung membrane permeability.
      The mean Kep values of healthy controls (0.78+/-0.13 for left lung, 0.79+/-0.14
      for right lung) were significantly lower than HCV Ab+ patients (1.10+/-0.31 for
      left lung, 1.11+/-0.34 for right lung, P<0.001). But no significant change was
      observed in PFT (P>0.05). We conclude that subclinical alveolitis and/or
      interstitial lung disease may be present in patients with HCV Ab+, since it is
      known that an increase in the epithelial permeability of the lung is an early
      manifestation of interstitial disease.

PMID- 11973485
TI  - Follow-up of perfusion defects in pulmonary perfusion scanning after pulmonary
      embolism: are we too careless?
AB  - Persisting perfusion defects may still be found in pulmonary perfusion
      scintigraphy months or years after pulmonary embolism. The aim of this study was
      to investigate the rate of persisting perfusion defects and the pattern of
      scintigraphic follow-up of patients after pulmonary embolism. Only those patients
      were included into our study who received pulmonary perfusion scintigraphy
      between 1991 and 1999, and who had perfusion defects including at least one whole
      segment. These perfusion defects were considered as persisting perfusion defects
      if unchanged over at least 1 year. From 3640 patients examined, 451 (12.4%) had
      perfusion defects meeting the criteria of this study. Of those, 129 (28.6%)
      received a scintigraphic follow-up. In 62 patients (48.1%), a reperfusion of the
      defects was found. In 38 patients (29.5%), the defects persisted within a follow
      up period of up to 12 weeks. However, no pulmonary perfusion scintigraphy was
      performed thereafter. Out of the 129 patients receiving a scintigraphic follow
      up, only 29 (22.5%) had a follow-up over more than 1 year, 19 of those had
      persisting perfusion defects. It is concluded that our data show an inadequate
      scintigraphic follow-up of patients with pulmonary embolism which may lead to
      unnecessary anticoagulant treatment if persisting perfusion defects are
      misinterpreted as fresh pulmonary embolism. In many cases, there was no further
      follow-up even if reperfusion of the defects was lacking in early follow-up.

PMID- 11973486
TI  - Assessment of the diagnostic capacity of planar scintigraphy and SPECT with 99mTc
      HMPAO-labelled leukocytes in superficial and deep sternal infections after median
      sternotomy.
AB  - Sternal infection is a rare complication of median sternotomy but is associated
      with considerable morbidity and mortality, particularly in the case of deep
      sternal infection (mediastinitis). Successful treatment depends on early
      diagnosis and on the location (deep or superficial) of the infection.
      Radiological techniques have many limitations, and although 67Ga scintigraphy is
      effective, it delays diagnosis by 48 h. We assessed the diagnostic capacity of
      planar scintigraphy and single photon emission computed tomography (SPECT) with
      99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled leukocytes in deep sternal
      infections after median sternotomy. We prospectively studied 41 patients with
      clinical suspicion of deep sternal infection 4 and 20 h after administration of
      the tracer. The final diagnosis was deep sternal infection in nine patients and
      superficial sternal infection in 10, with infection being ruled out in 22
      patients. Planar scintigraphy did not detect any of the deep sternal infections
      at either 4 h or 20 h. SPECT correctly identified eight of the nine deep sternal
      infections at 4 h and all seven at 20 h, with no false positive results. Planar
      scintigraphy identified 16 of the 18 superficial sternal infections at 4 h and
      all of them at 20 h. SPECT identified 17 of these 18 infections at 4 h and all of
      them at 20 h. Other infections unrelated to the sternotomy were identified in
      seven patients. Leukocytes labelled with 99mTc-HMPAO are a highly reliable method
      for the early diagnosis of sternal infections after median sternotomy. Use of
      SPECT allows determination of the depth of the infection and differentiation of
      superficial from deep sternal infections. It is also possible to detect other
      sites of infection, thus providing alternative diagnoses.

PMID- 11973487
TI  - Uptake and washout of 99mTcV-dimercaptosuccinic acid and 99mTc-sestamibi in the
      assessment of histological type and grade in breast cancer.
AB  - This study was performed to investigate the relationship between histological
      type and grade, with the uptake and washout of 99mTc-hexakis-2
      methoxyisobutylisonitrile (99mTc-sestamibi, 99mTc-MIBI) and 99mTcV
      dimercaptosuccinic acid (99mTcV-DMSA) in breast cancer. Forty-five patients with
      histologically proven breast cancer had previously been referred for 99mTcV-DMSA
      and/or 99mTc-MIBI scintimammography. Twenty-five of them underwent both 99mTcV
      DMSA and 99mTc-MIBI scintigraphy in a double phase study. Lateral prone and
      anterior supine images were acquired at 15 and 60 min after administration of 740
      925 MBq of each radiotracer. Uptake ratios and retention index were calculated
      and correlated with histology and grade of malignancy. Histology showed eight
      different histotypes: 77.7% were infiltrating ductal or lobular carcinomas.
      Mammography was definitely positive in 32/45, indeterminate in 10 and negative in
      three cases (sensitivity 71%). 99mTcV-DMSA was true positive in 37/40
      (sensitivity 92.5%) and 99mTc-MIBI in 28/30 (sensitivity 93.3%) breast cancers.
      Uptake ratios were significantly higher in ductal than in lobular carcinomas on
      99mTcV-DMSA and 99mTc-MIBI scintigrams at early and delayed phases. Grade II
      carcinomas had significantly lower values of retention index (rapid washout) than
      grade III carcinomas. This finding was statistically significant only on 99mTc
      MIBI scans and was observed in ductal and lobular carcinomas. The retention index
      did not show any significant difference between ductal and lobular carcinomas.
      Uptake ratios were also not statistically different between grade II and III
      cancers. It is concluded that 99mTc-MIBI and 99mTcV-DMSA uptake in breast cancer
      is probably related to histological type and may distinguish ductal from lobular
      carcinomas. To a certain degree, the washout rate may reflect the histological
      grade, but since grade is not the only factor influencing this phenomenon it
      should be explored further in conjunction with other parameters by multivariate
      analysis in order to clarify eventual indirect correlations.

PMID- 11973488
TI  - Usefulness of CT scan, MRI and radiocholesterol scintigraphy for adrenal imaging
      in Cushing's syndrome.
AB  - The aim of this study was to evaluate the sensitivity and accuracy of computed
      tomography (CT) scanning, 75Se-selenomethyl-norcholesterol scintigraphy (SNS) and
      magnetic resonance imaging (MRI) in patients with Cushing's syndrome (CS)
      undergoing adrenalectomy. A series of 67 patients with CS due to benign adrenal
      disease was reviewed. There were 11 (16.4%) men and 56 (83.6%) women, with an
      overall median age of 44 years (range 19-69 years). Prior to surgery all patients
      underwent both CT and SNS, and 58 (86.6%) underwent adrenal MRI. Thirty-five
      (52.2%) of the patients (group A) had histologically confirmed unilateral adrenal
      involvement (33 patients with a solitary adrenocortical adenoma, and two with
      unilateral nodular cortical hyperplasia), while 32 (47.8%) of the patients (group
      B) had CS caused by bilateral adrenal involvement, including two patients with
      multinodular adrenal hyperplasia. The sensitivity, specificity and accuracy of
      adrenal imaging in group A were 97.1%, 100% and 98.5% for SNS, 94.3%, 68.7%
      (P<0.05, chi2 test) and 82.1% for CT scan, and 92.3%, 60.0% (P<0.05) and 64.3%
      (P<0.05) for MRI, respectively. In group B the sensitivity, specificity and
      accuracy were 100%, 97.2% and 98.5% for SNS, 64.5% (P<0.05), 97.2% and 82.1% for
      CT scan, and 60.0% (P<0.05), 92.3% and 35.7% (P<0.05) for MRI, respectively. In
      conclusion, SNS represents the most sensitive and specific adrenal imaging study
      and should be used in all patients with confirmed biochemical diagnosis of CS
      undergoing adrenalectomy. The sensitivity and specificity of CT scan and MRI are
      similar, but the latter shows a lower accuracy, especially in patients with
      bilateral adrenal involvement.

PMID- 11973489
TI  - Reproducibility and clinical value of 18F-fluorodeoxyglucose positron emission
      tomography in recurrent melanoma.
AB  - The purpose of this study was to assess the reproducibility and clinical impact
      of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in
      patients with (suspected) recurrent melanoma. The clinical value of PET was
      prospectively measured in 58 consecutive patients referred for PET because of
      unresolved clinical questions after conventional work-up. Diagnostic
      understanding and therapy choice by referring physicians were evaluated before,
      directly after, and 6 months after PET. Observer agreement of PET readings was
      measured with respect to various parameters (interpretation, number and
      localization of lesions, 'clinically decisive' metastases), using intra-class
      correlation coefficients. FDG PET improved diagnostic understanding in 33 cases
      (57%). In six patients (10%), diagnostic understanding was solely based on PET
      information. According to the attending clinicians, PET contributed to a positive
      change of planned treatment in 23 patients (40%) and increased confidence in the
      chosen treatment in 23 (40%). Observer agreement of PET readings was very high
      (intra-class correlation coefficients were between 0.87 and 0.94). The diagnostic
      value related especially to the whole-body scan technique and the superior
      specificity, compared to conventional work-up. It is concluded that, in
      problematical cases with (suspected) recurrent melanoma, 18F-FDG PET had
      considerable impact on diagnostic understanding and management. Together with the
      excellent observer reliability, these results justify further studies to
      determine the optimal place of PET in routine diagnostic algorithms in recurrent
      melanoma.

PMID- 11973490
TI  - UK audit of single photon emission computed tomography reconstruction software
      using software generated phantoms.
AB  - The purpose of this study was to undertake an audit of the quantitative
      characteristics of single photon emission computed tomography software using
      projection data from an analytically generated software phantom and a measured
      line source. The phantom consisted of three structures. A uniformly filled
      cylinder, a series of cylindrical rods of various diameters in a background
      activity with a rod to background ratio of 2:1 and lastly, a set of three
      concentric rings of activity in the ratio 1:0:1. The phantom contained no added
      statistical noise. No attenuation was imposed on the data. The phantom was
      generated analytically and projections were distributed at six different count
      densities. A single set of projections from a thin line source was also
      distributed. These data were distributed to centres throughout the UK. Centres
      were asked to reconstruct the data using a 'ramp only' reconstruction with no
      additional smoothing function applied. Data were requested for mean and standard
      deviation in the uniform cylinder, the maximum counts for each cylindrical rod
      and the mean counts in regions placed within the concentric rings. For the
      measured line source, centres were asked to measure the full width at half
      maximum and peak pixel counts for a profile through the reconstructed line.
      Results from 115 systems were obtained from 100 centres throughout the UK. These
      provided data from 12 software providers, 11 of these being commercial companies.
      Data were compared with the known input values and histograms of the distribution
      of results obtained. Significant differences in quantitative parameters were
      noted for the different input count densities as well as between suppliers and
      revisions of software from single suppliers.

PMID- 11973492
TI  - Factors influencing the accuracy of renal output efficiency.

PMID- 11973491
TI  - Optimization of the small-scale synthesis of DOTA-Tyr3 -octreotide.
AB  - The clinical potential of 111In and 90Y labelled 1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid conjugated Tyr3-octreotide (DOTA-TOC) have been
      reported in a number of publications, and Phase II clinical trials of 90Y-DOTA
      TOC are currently in progress. However, to date, only a summary of the large
      scale preparation of these radiopharmaceuticals has been published. This
      publication aims to describe our experience of the small-scale synthesis of DOTA
      TOC in the hope that this will assist others in the preparation of this and other
      similar radioconjugates. DOTA in the form of the tri-t-butyl ester was coupled to
      the Lys5 (BOC) protected Tyr3-octreotide in N,N-dimethylformamide or N-methyl-2
      pyrolidinone, in a three-step reaction involving conjugation, using O-(7
      azabenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and
      diisopropylethyamine (DIPEA) as coupling reagents, deprotection with
      trifluoroacetic acid and HPLC purification of the conjugates. The product was
      obtained in final yields of 60+/-5%. The purified product was characterized by
      mass spectroscopy, showing a molecular weight of 1421.55+/-0.08. In somatostatin
      receptor binding assays, the unlabelled DOTA-TOC showed an effective displacement
      of 99mTc labelled HYNIC-TOC (where HYNIC is hydrazinonicotinamide) (IC50=0.31+/
      0.07 nm), confirming the retention of receptor-binding affinity. The conjugate
      could be efficiently labelled with 111In by addition of 111InCl3 and ammonium
      acetate buffer pH5 and heating (95 degrees C, 20 min).

PMID- 11973493
TI  - Color Doppler sonography and scintigraphy of the testis: a prospective,
      comparative analysis in children with acute scrotal pain.
AB  - OBJECTIVE: To compare testicular color Doppler sonography with testicular
      scintigraphy in differentiating between surgical and nonsurgical conditions of
      the pediatric testis, and to evaluate the role of testicular color Doppler
      sonography in the pediatric population. MATERIALS AND METHODS: Forty-six children
      (age range, 1 day to 18 years; median age, 11 years) with acute scrotal pain were
      evaluated with both scintigraphy and color Doppler sonography by two separate
      groups of radiologists who had no knowledge of the results of the other modality.
      The final radiologic diagnosis was classified as a surgical condition,
      nonsurgical condition, or indeterminate and was compared with the patient's
      surgical diagnosis or clinical diagnosis, which was established by response to
      treatment and follow-up. RESULTS: Sonography correctly diagnosed 11 of 14
      surgical conditions and 31 of 32 nonsurgical conditions. There was one
      indeterminate sonogram. There were no false-positive examinations, and there were
      three false-negative examinations (sensitivity = 78.6% [95% CI, 66.7-90.5%],
      specificity = 96.9% [95% CI, 94.3-99.5%], accuracy = 91.3%). Color flow was
      demonstrated in the asymptomatic testis in 34 of 44 boys. Scintigraphy correctly
      diagnosed 11 of 14 surgical conditions and 29 of 32 nonsurgical conditions. There
      were two indeterminate scintigrams. There were two false-positive examinations
      and two false-negative examinations (sensitivity = 78.6% [95% CI, 66.7%-90.5%],
      specificity = 90.6% [95%CI, 82.2%-99.0%], accuracy = 87.0%). CONCLUSIONS: Color
      Doppler sonography and scintigraphy show similar sensitivity for the diagnosis of
      testicular torsion. A small number of false-negative cases can occur with either
      modality. The two studies may provide complementary information in indeterminate
      cases.

PMID- 11973494
TI  - Comparison of two benzodiazepines used for sedation of children undergoing
      suturing of a laceration in an emergency department.
AB  - OBJECTIVES: (1) To determine if oral diazepam (POD) is as effective in sedating
      children less than 6 years of age for laceration repair as oral midazolam (POM)
      or intranasal midazolam (INM); and (2) To determine if patients stayed longer in
      the department after sedation when given POD for sedation. DESIGN/METHODS: Block
      randomized, single-blind trial. SETTING: Tertiary pediatric emergency department.
      PARTICIPANTS: Patients 1 to 5 years old with a laceration requiring sutures were
      enrolled. INTERVENTIONS: All patients had topical anesthetic applied to the wound
      and were randomly assigned to POD 0.5 mg/kg, POM 1.0 mg/kg, or INM 0.4 mg/kg for
      sedation. RESULTS: One hundred twenty-nine patients were enrolled, 42 POD, 45
      POM, and 42 INM. Each group was similar at baseline for age, heart rate,
      respiratory rate, blood pressure, oxygen saturation, previous laceration or
      sedation, anxiety score, and site of laceration. POM and POD were better
      tolerated than INM (P = 0.05 and 0.034), respectively. Time to sedation was
      significantly longer in POD (31.0 +/- 9 min) than INM (26.1 +/- 9 min) (P =
      0.011) but there was no significant difference when comparing the other groups.
      However, this difference was not clinically significant. POD was significantly
      worse at sedating children compared with POM and INM on all four scores (ie,
      doctor, nurse, parent, and investigator), but INM and POM were equivalent. Total
      time in the department was no different between POM and INM or POM and POD, but
      was significantly different for POD (53.9 +/- 16 min) and INM (48 +/- 12 min);
      however, this difference was minimal. More patients were said to be drowsy at
      home in the POM group (51%) than the POD group (32%). CONCLUSIONS: The oral route
      of delivery of POM and POD was better tolerated than INM. POM and INM were more
      effective at sedation than POD, but there was no clinical difference between any
      groups for time to sedation or time to discharge. More patients in the POM group
      had side effects after leaving the department. POD may be an alternative to POM,
      but a higher dose may be required, possibly with longer recovery times.

PMID- 11973495
TI  - Is a complete trauma series indicated for all pediatric trauma victims?
AB  - OBJECTIVE: Trauma series radiographs (ie, lateral cervical spine, anteroposterior
      chest, and anteroposterior pelvis) are routinely recommended for victims of
      multiple trauma. However, the utility of the chest and pelvic radiographs has
      never been adequately evaluated. The purpose of this study is to determine
      whether clinical findings alone predict the results of these radiographs.
      METHODS: The pediatric radiology department at the Jacobi Medical Center, Albert
      Einstein College of Medicine, Bronx, New York, maintains a log of all patients
      who have undergone a complete trauma series. From this group, we selected all
      patients younger than 2 years with a Glasgow Coma Scale greater than 14 points.
      The patients' emergency department charts were reviewed to note the presence or
      absence of localizing signs and symptoms referable to the chest and pelvis,
      including chest or pelvic pain, tenderness, ecchymoses or abrasions, shortness of
      breath or other respiratory symptoms, hematuria or difficulty voiding, and
      abdominal distention. RESULTS: Sixteen of the 91 subjects (18%) had localizing
      chest findings. Two of these patients had positive chest radiographs, whereas the
      75 patients without localizing chest findings had no positive chest radiographs
      (P < 0.03). Thirty-two of 91 subjects (35%) had localizing pelvic signs. Five of
      these patients had positive pelvic radiographs, whereas the 56 patients without
      localizing pelvic signs had no positive pelvic radiographs (P < 0.01). The
      negative predictive value of localizing signs and symptoms was 100% for both
      chest and pelvic radiographs. CONCLUSION: These data suggest that if an adequate
      examination can be performed, trauma series radiographs can be ordered
      selectively, based on the patient's clinical findings.

PMID- 11973496
TI  - Commercial airline travel decreases oxygen saturation in children.
AB  - OBJECTIVE: To investigate the degree of oxygen saturation decline occurring in
      children during prolonged commercial air travel. METHODS: Oxygen saturation and
      heart rate were measured with a pulse oximeter in healthy pediatric passengers at
      sea level before boarding a commercial aircraft. These measurements were repeated
      after 3 hours and 7 hours of flight. Cabin pressure, true altitude, and cabin
      fraction of inspired oxygen (FiO2) were also recorded at 3 hours and 7 hours.
      RESULTS: Eighty healthy children (43 boys) aged 6 months to 14 years were studied
      during eight flights between Honolulu, Hawaii, and Taipei, Taiwan. Oxygen
      saturation declined, and heart rate increased after 3 hours (95.7%, 105 beats per
      minute [BPM]) and 7 hours (94.4%, 108 BPM) of flight compared to preflight levels
      at sea level (98.5%, 100 BPM) (P < 0.001). The 3-hour to 7-hour oxygen saturation
      and heart rate means differed significantly (P < 0.001, P = 0.014, respectively).
      The significant drop in oxygen saturation was associated with the decreased cabin
      partial pressure of oxygen (PO2)--PO2 was 159 mm Hg at sea level, 126 mm Hg after
      3 hours, and 124 mm Hg after 7 hours--but the 3-hour and 7-hour difference
      suggests that flight duration may also contribute to worsened oxygen
      desaturation. CONCLUSION: Oxygen saturation declines significantly during
      commercial airline travel with reduced aircraft cabin pressure and concomitant
      reduced cabin PO2. We did not observe an "acclimation" of oxygenation as the
      length of travel increased; rather, the oxygen saturation decline worsened,
      although it may be partially a result of the lower cabin PO2. Although there were
      no clinically noticeable ill effects at the level of oxygen saturation decline in
      these relatively healthy passengers, patients with preexisting anemia or
      cardiopulmonary disease are likely to experience greater degrees of clinical
      compromise with similar degrees of oxygen saturation decline.

PMID- 11973497
TI  - Assessment of pediatric patients by emergency medical technicians-basic.
AB  - OBJECTIVE: To determine whether emergency medical technicians-basic can
      accurately assess children and whether this ability varies with the patient's age
      or diagnosis. This determination is important for educational program design for
      emergency medical technicians in pediatrics and for evaluation of the possibility
      of expanding their scope of practice. DESIGN: Retrospective chart review.
      SETTING: Pediatric emergency department in a large, urban hospital. PARTICIPANTS:
      Patients (n = 2430) presenting to the pediatric emergency department via basic
      life support ambulance during a 12-month period. MEASUREMENTS: Data collected
      were name, age, field assessment (FA), and emergency department (ED) diagnosis.
      Patient's ages were organized into five groups: infant (0-1 y), toddler (1-3 y),
      preschool (3-6 y), school-aged (6-11 y), and adolescent (> 11 y), and the ED
      diagnoses were divided into seven categories. The accuracy of the FA was compared
      with the ED diagnosis. We then analyzed FA accuracy by patient's age and type of
      diagnosis. The chi(2) contingency table analysis was used for dichotomous
      variables (P < 0.05). In addition, logistic regression and stratified analysis
      were used. Both ambulance and hospital charts were available for 2064 patients.
      Age ranged from birth to 19 years with a bimodal distribution at the extremes of
      patient age and a mean age of 8.25 (SD, 5.64). The distribution was 11.7% (241)
      infants, 14.7% (303) toddlers, 14.9% (307) preschool, 21.2% (437) school-aged,
      and 37.6% (776) adolescents. RESULTS: Overall emergency medical technician-basic
      assessment was accurate 81.5% (1683) of the time. There was a statistically
      significant variation in accuracy with both age group (chi(2) = 40.07, P < 0.05)
      and diagnostic category (chi(2) = 185.7, P < 0.05). By age group, the accuracy of
      field assessment was 69.7% (168) infants, 75.9% (230) toddlers, 82.7% (254)
      preschool, 86.7% (379) school-aged, and 84.0% (652) adolescents. By category of
      diagnosis, the accuracy of the field assessment was 92.4% (292) major trauma,
      91.4% (478) minor trauma, 88.9% (112) psychologic and social, 85.1% (229) major
      medical, 81.1% (180) wheezing-associated respiratory illness, 65.4% (350) minor
      medical, and 57.5% (42) non-wheezing-associated respiratory illness. CONCLUSIONS:
      Emergency medical technicians-basic were highly successful in assessing children
      with wheezing, serious illness, injuries, and psychologic and social conditions.
      Consideration should be given to expanding their scope of practice in these
      areas. They were less successful in assessing minor medical conditions and
      respiratory emergencies other than wheezing. They require additional training in
      these areas.

PMID- 11973498
TI  - Isolated extradural hematoma in children presenting to an emergency department in
      Australia.
AB  - BACKGROUND: Isolated extradural hematoma (EDH) is becoming more frequently
      recognized in emergency departments (EDs) in children. We describe the natural
      history of children with isolated EDH presenting to a large Children's Hospital
      ED. METHODS: This is a descriptive case series study using a retrospective review
      of the medical records of children presenting to the ED with a diagnosis of
      isolated EDH over 8 years. Comparison was made with children having other
      injuries in addition to EDH. The cause, nature of injury, presentations to
      hospital, management, outcome, and any association with nonaccidental injuries
      (NAI) were analyzed. RESULTS: Of the 35 cases with a final diagnosis of isolated
      EDH initially presenting to the ED, 70% were over 3 years of age (mean 6.6
      years), and 60% were boys. A fall of less than half a meter was the cause of
      isolated EDH in 51.4% of patients. The remaining cases resulted from a fall from
      a height greater than half a meter (17.1%), a motor vehicle accident (11.4%),
      being hit by an object (8.6%), a bicycle accident (5.7%), and a skateboard
      accident (5.7%). Children younger than 3 years presented within 24 hours of
      injury in 70% of cases, compared with 65% of older children. In 95% of cases,
      presentation was nonspecific, suggesting a medical rather than a surgical
      problem. This resulted in a delay in seeking emergency care and a delay in final
      diagnosis for these patients. Surgical drainage was required in 68.6% of cases,
      with older children being more likely to be managed conservatively. In 23.4% of
      cases, minor residual neurologic deficit occurred; there were no cases of serious
      long-term problems. There were no cases of NAI in the children studied.
      CONCLUSION: This report highlights falls as a common cause of isolated EDH in
      children. Delay in presentation for clinical assessment is common, because many
      children have nonspecific presentation that is suggestive of a medical problem.
      No cases of NAI were reported in this study.

PMID- 11973499
TI  - Child abuse presenting as pseudorenal failure with a history of a bicycle fall.

PMID- 11973500
TI  - Solitary epithelial cyst of the uvula in the neonate: case reports and review of
      the literature.

PMID- 11973501
TI  - Management of penetrating scrotal injury.

PMID- 11973502
TI  - Elemental mercury as an attractive nuisance: multiple exposures from a pilfered
      school supply with severe consequences.

PMID- 11973504
TI  - Abdominal pain for 3 days, but now the patient is feeling better.

PMID- 11973503
TI  - Massive embolic myocardial infarction in a teenager.

PMID- 11973505
TI  - Securing the child's airway in the emergency department.
AB  - Airway management is an important aspect of pediatric emergency care. Prompt,
      effective airway access can mean the difference between a good outcome and
      disability or death. Optimal management requires an understanding of the
      differences between children and adults with respect to airway anatomy and
      physiology and response to medications to facilitate airway access. In most
      cases, the emergency physician is called to secure a child's airway with little
      forewarning. This review details a logical and practical approach to the
      uncomplicated pediatric airway. Emphasis is also placed on recognition of the
      difficult airway and methods to render the difficulty less daunting. Good
      judgment and the appropriate skills are the prerequisites for success.

PMID- 11973506
TI  - Infectious diseases.

PMID- 11973507
TI  - A procedure for placing pediatric femoral venous catheter tips near the right
      atrium.
AB  - OBJECTIVE: To find a body measurement that would serve as an index for
      determining the length of femoral venous catheter to be inserted to achieve a
      position near the right atrium. METHODS: A candidate index measurement was
      chosen, and radiographic measurements of routine femoral venous catheter
      placements were compared with the placement that may have resulted from use of
      the index in a group of patients. In a subsequent group, the candidate index was
      used to choose catheter insertion length, the accuracy of which was again
      evaluated from routine placement radiographs. RESULTS: The first series of
      radiographic measurements predicted that use of the sternal-umbilical-puncture
      (SUP) index would result in acceptable and accurate catheter tip placement. This
      was confirmed in the second group of patients in which 11 of 12 catheter tips
      were within 1 cm of the target position. CONCLUSIONS: The use of the SUP index
      ensures acceptable accuracy in estimating the required insertion length of
      femoral catheter when tip placement near the right atrium is the clinical goal.

PMID- 11973508
TI  - Pediatric emergency medicine: legal briefs.

PMID- 11973509
TI  - Kids speak: effective communication with the school-aged/adolescent patient.
AB  - Caring for school-aged and adolescent children presents unique challenges to the
      acute healthcare provider. In today's healthcare industry, children should be
      informed and should participate in the medical decision-making process. Thus, the
      art of successful school-aged and adolescent communication is vital in today's
      economically driven market. Practitioners evaluating pediatric patients must
      immediately establish a rapport and trust--not only with the parents, but also
      with the child--through effective communication techniques. Effective
      communication skills and challenges are discussed, along with current research
      trends to improve patient-provider relations.

PMID- 11973513
TI  - [Epidemiology: is twin pregnancy a public health problem? The gynecologists point
      of view].

PMID- 11973514
TI  - [The pediatrics point of view].

PMID- 11973515
TI  - [Growth discordance in dichorionic twin pregnancies: risk factors, diagnosis and
      management].
AB  - OBJECTIVE: To analyse the risk factors and perinatal consequences of growth
      discordance among dichorionic twin pregnancies. Subjects and methods. A cohort of
      346 dichorionic twin pregnancies delivered at one institution between January
      1996 and December 1999 was analyzed. Two groups were compared, according to the
      presence or absence of growth discordance (n=72 and 274, respectively). Birth
      weight discordance was defined as a difference of 20% or more of the weight of
      the heavier twin, associated with an intra-uterine growth restriction (10(th)
      percentile) of at least one twin. Ultrasound discordance was defined as a
      difference of estimated fetal weight>20%. The two groups were compared by
      univariate and multivariate analysis. RESULTS: The main risk factors for birth
      weight discordance in multivariate analysis were ovulation induction (OR=1.6 [1.0
      2.4]), multifetal pregnancy reduction (OR=2.3 [1.3-4.2]), and fetal malformations
      (OR=2.4 [1.0-5.4]). Ultrasound shows a poor performance in predicting discordance
      with a sensitivity of 55.6%, a specificity of 94.2%, a positive predictive value
      of 71.4% and a negative predictive value of 89.0%. Birth weight discordance was
      associated with a poor fetal and neonatal outcome: gestational age at delivery
      was 34.4 weeks versus 35.4 weeks, there were more caesarean deliveries (OR=1.9
      [1.3-2.8]), a higher perinatal mortality (OR=3.7 [1.6-8.5]), and more neonatal
      intensive care unit admissions (OR=1.8 [1.2-2.7]). Multivariate analysis shows
      that growth discordance is an independent risk factor for mortality but not for
      cerebral adverse outcome or respiratory distress syndrome. CONCLUSION: Ovulation
      induction and multifetal pregnancy reduction are independent risk factors for
      twin birth weight discordance, which carries a poor perinatal prognosis.

PMID- 11973516
TI  - [Prenatal conflict of interest between twins: malformations and chromosome
      anomalies].

PMID- 11973517
TI  - [Twin delivery: facts and controversies].

PMID- 11973518
TI  - [Specific care for twins during their first hospitalization].

PMID- 11973519
TI  - [Psychological consequences of twinship on the children and their parents].
AB  - This paper presents a synthesis about the psychological consequences of twinship
      based on a review of the literature and on our clinical experience. During
      pregnancy, delivery and the immediate post-partum, mothers experience physical
      and psychological difficulties linked with increased medical risks for themselves
      and for the children. The twins mortality is high before and after delivery.
      Grieving for one twin creates particular problems for parents. During first
      months after hospital discharge mothers encounter material and emotional stress.
      They are caused by overload of mothering tasks and the specificity of mother
      twins relationship. The impossibility to establish a dyadic relationship with
      each child creates feelings of frustration and guilt. The risk of child abuse is
      increased in twins. The balanced psychoemotional development of twins requires
      parental attitudes enhancing their individualization as opposed to their
      "collectivization". The risk of prematurity is ten times increased in twins which
      increases the risks of developmental disabilities. Considering that the number of
      twin deliveries is rising in our country it is important to be aware of the
      problems experienced by the families and to improve the way material and
      psychological help is provided to them.

PMID- 11973520
TI  - [Current clinical implications of transvaginal ultrasound measurement of the
      cervix during pregnancy].
AB  - Transvaginal ultrasound measurement of the cervix is increasingly used for the
      prediction of preterm labor. In comparison to clinical vaginal examination, it
      has the advantages of being highly reproducible, with a low inter-observer
      variability, and of offering an evaluation of the entire cervical canal,
      including the internal os. The sensitivity and specificity of transvaginal
      ultrasound have been validated by several studies in women with symptoms of
      preterm labor, however its clinical applications and its limits have yet to be
      fully determined. It is likely to be of benefit in the management of multiple
      gestations, but it appears unlikely to be of use in low-risk pregnancies.
      Finally, whether it can be applied to estimate the risk of cervical incompetence,
      or to determine the need for cervical cerclage placement has not yet been
      determined by methodologically satisfactory clinical studies.

PMID- 11973521
TI  - [Isolated antenatal pyelic dilatation: postnatal follow-up and care for vesico
      ureteral reflux].
AB  - OBJECTIVE: To assess the risk of aneuploidia in case of isolated antenatal pyelic
      dilatation and to detail urological care for these children. METHODS: Prenatal
      and postnatal follow-up was analyzed in 350 cases. RESULTS: The overall rate of
      chromosome anomalies was 1.3%. Trisomy 21 was found alone in one case (0.3%). The
      sex ratio was 26% girls and 74% boys. Vesico-ureteral reflux was similar in both
      sexes (13%). CONCLUSION: The question of proposing karyotyping in case of
      isolated pyelic dilatation remains unsolved because minimal subjective signs such
      as slightly excessive amniotic fluid can completely change the assessment of the
      risk of aneuploidia. The frequency of postnatal vesico-ureteral reflux associated
      with prenatal pyelic dilatation warrants complete prenatal ultrasound screening.

PMID- 11973522
TI  - [Contribution of Doppler exploration of ductus venosus flow].
AB  - Among the different means currently available to assess fetal hypoxia and
      determine the optimal time for fetal extraction in case of intra-uterine growth
      retardation (IUGR), Doppler measurement of blood flow in the ductus venosus (DV)
      is one of the most promising. The DV is one of the three fetal circulation shunts
      observed in utero. Approximately 55% of the oxygenated blood flowing from the
      umbilical vein to the foramen ovale and the left cavities short circuits the
      hepatic circulation via the DV. This oxygenated blood is preferentially directed
      to the myocardium and the brain. Measurement errors (suprahepatic veins,
      umbilical veins) can lead to erroneous diagnosis of defective DV. Inversely,
      there is a normal physiological reverse flow in the suprahepatic veins and the
      inferior vena cava not present in the DV. In case of fetal hypoxia, the
      proportion of oxygenated blood increases due to increased flow from the umbilical
      vein into the DV, increasing the proportion of oxygenated blood delivered to the
      heart and brain instead of the liver. This corresponds to fetal adaptation to
      hypoxia and the spectrum of the DV thus normally includes a positive wave. When
      the fetus is unable to adapt to hypoxia, there is an alteration of the right
      heart function observable in the DV spectrum with diminished diastolic flow or
      even zero or reverse flow. Anomalous CV flow is a sign of major deterioration of
      the fetal status before development of severe anomalies. For many, the short-term
      variability implies immediate extraction of the fetus. Certain well trained teams
      combine DV flow with other information such as the biophysical examination of the
      fetus, the quality of the amniotic fluid, visual and automated growth retardation
      measurements, and other Doppler measurements for decision making. Doppler
      measurements of the DV, disclosing IUGR or made during surveillance of IUGR, are
      theoretically made only if other Doppler findings such as arterial redistribution
      are abnormal. Doppler assessment of DV flow is not a first intention procedure
      and only concerns a small high-risk fetal population. Experience and good
      knowledge of fetal anatomy and the Doppler technique are required (it is easy to
      confuse the physiological spectrum of the suprahepatic veins with a negative wave
      corresponding to pathological DV flow).

PMID- 11973524
TI  - [Third trimester medical termination of pregnancy and death in the postnatal
      period. Introduction].

PMID- 11973523
TI  - [Confined placental mosaicism: definition, consequences and outcome].
AB  - Confined placental mosaicism (CPM) occurs in approximately 2 per cent of viable
      pregnancies studies by chorionic villus sampling. The great majority of
      pregnancies with confined placental mosaicism proceed uneventfully, resulting in
      normal liveborn infants. However, a few specific chromosomal abnormalities have
      been associated with fetal growth retardation. Fetal karyotype should be checked
      by amniocentesis and such pregnancies should have careful ultrasound follow-up.

PMID- 11973525
TI  - [Indications, techniques and complications of third trimester termination].

PMID- 11973526
TI  - [Patients' and professionals'opinions on third trimester termination of
      pregnancy].
AB  - The aims of this paper are to present a review of the literature on the
      patients'and professionals'opinions about third trimester termination of
      pregnancy and to give the main results of two studies that we have recently
      conducted. On the whole, publications indicate that the patients'distress is not
      linked with the moment when pregnancy is terminated. However questions about the
      fetus death, in utero feticide, and the organization of funerals remain sensitive
      and communication with patients on these matters needs to be improved. Studies in
      other countries indicate that professionals are not prepared to recommend late
      terminations of pregnancy mainly because the fetus is viable and should be
      considered as a patient. The mother's and the couple's point of view seem not to
      be enough taken into account. French obstetricians seem to consider more
      acceptable third trimester TOP than their european colleagues. For them, not
      setting a limit to the gestational age allows more thorough evaluation of the
      diagnosis and more parental reflection. They mention major ethical dilemmas,
      independently from gestational age, and suggest that current practices should be
      openly debated.

PMID- 11973527
TI  - [Psychological impact of late termination of pregnancy].

PMID- 11973528
TI  - [Limitation of intensive care and infant death during the postnatal period].
AB  - The primary goal of neonatal intensive care is to save the life of all newborns,
      recognized as a complete human being despite their life-threatening situation.
      There are situations however where extensive and irreversible brain damage
      leading to major handicaps is the cost of saving the infant's life. In these
      extreme situations, where the infant may or may not yet depend totally on life
      support systems, the physicians in charge are faced with the question of whether
      medical interruption of the infant's life could be an ethical option. We recall
      here the main phases of the discussions conducted by french neonatologists faced
      with these dilemmas and the fundamental principles of current recommendations.
      Interruption of infant's life in the neonatal unit could be a possible
      alternative to feticide performed during third trimester termination of
      pregnancy: in an ethic and coherent medical and human approach, it would be
      possible to envisage termination of life during the postnatal period in certain
      specific cases at the request of the parents.

PMID- 11973529
TI  - [Accompanying babies to death after late termination of pregnancy].
AB  - When feticide, necessary within the framework of late termination of pregnancy,
      cannot be achieved before delivery for medical reasons or because the act is
      refused by the parents, we propose as an alternative, to accompany the baby to
      death in the neonatology unit. This approach can be seen as palliative care
      despite the ethical and legal issues it raises. It can be an appropriate response
      to the parents' distress when moral and religious beliefs are contradicted by
      medical reality. This situation remains exceptional and must be envisaged case by
      case. The decision to institute the principle of accompanying babies to death was
      made after open discussion conducted for many years among neonatologists. The
      final decision cannot however be made until the obstetrical and pediatric teams
      have reached a sufficient degree of reciprocal confidence.

PMID- 11973530
TI  - [Thoracic scoliosis: exothoracic and endothoracic deformations and the spinal
      penetration index].
AB  - PURPOSE OF THE STUDY: We reviewed retrospectively our patients with thoracic
      lordoscoliosis and conducted a conceptual analysis of the patients with airway
      compression and atelectasia due to anterior protrusion of the vertebral bodies in
      order to describe the pathological conditions involved and the management methods
      used. Our goal was to develop a new concept for quantifying thoracic deformation.
      The individual cases discussed here have been reported earlier, but this is the
      first series analysis to date. MATERIAL AND METHODS: Eighteen patients, aged 7.3
      to 18 years, with thoracic lordoscoliosis due to a variety of causes, mostly
      neuromuscular disorders (12 cases), are described. Most patients were treated by
      anterior subtotal periosteal resection of the vertebral body followed by
      posterior instrumentation and arthrodesis. RESULTS: Atelectasia disappeared with
      a normalization of blood gases but the effect was variable on vital capacity. The
      analysis of the CT studies led to the concept of spinal deformity as an
      endothoracic deformation resulting from protrusion of the vertebral body into the
      thorax, the endothoracic vertebral hump. This concept was developed and
      quantified leading to the definition of a new index: the spinal penetration
      index. The spinal penetration index was obtained by tracing a line tangent to the
      posterior curve of the concave and convex ribs on each CT slice to determine a
      relationship between the real thoracic surface and theoretical thoracic surface
      measured with this tangent and the circumference of the thoracic cage. The index
      was expressed as a percent of the endothoracic surface occupied by the protruding
      veterbral body and the associated ribs. Calculated for each successive CT slice
      for the entire height of the thorax yielded a spinal penetration index
      quantifying the thoracic volume occupied by the spine. For the control
      population, we used CT series of the thorax obtained to search for pulmonary
      metastases in patients with malignant tumors. This gave a theoretical volume of 8
      to 10% occupied by the spine in normal subjects. In our patients with
      lordoscoliotic deformations we obtained real volumes of 15, 20 and even 50%.
      DISCUSSION: The spinal penetration index is an important morphological index of
      thoracic anatomy that measures the real volume of the functional thoracic
      cavities and which must be differentiated from vital capacity which measures both
      volume and function. This index can be used for pre- post-operative comparisons
      and constitutes a first step in 3-D assessment of thoracic spine deformations. It
      can also be used to classify spinal deformations and to make general
      recommendations concerning the management of both endothoracic humps and
      exothoracic rib humps.

PMID- 11973531
TI  - [Posterosuperior impingement of the shoulder in the athlete: results of
      arthroscopic debridement in 75 patients].
AB  - PURPOSE OF THE STUDY: The painful shoulder is a well-recognized clinical entity
      in throwers although the pathogenic mechanisms involved are still debated. In
      1991 Walch then Jobe developed the concept of posterosuperior impingement to
      explain lesions observed arthroscopically. This impingement between the deep
      aspect of the supraspinatus tendon and the glenoid occurs during loaded arm
      movements. The purpose of this work was to study the different types of lesions
      observed arthroscopically and to analyse outcome after arthroscopic debridement.
      MATERIAL AND METHOD: Our series included 75 thrower athletes who had shoulder
      pain for loaded arm movements. Pain was situated in the dominant shoulder in all
      cases. Clinically, the Jobe manipulation provoked pain in 52 patents, expression
      of a supraspinous disorder. After failure of conservative treatment, the patients
      underwent arthroscopy for assessment and debridement. At the time of arthroscopy,
      the patients had suffered pain for two years (mean 22.3 months). All 75 patients
      were seen for clinical and radiological assessment at least two years after
      arthroscopy. RESULTS: Among the 75 arthroscopies, there were 67 (89%) partial
      tears involving the deep aspect of the cuff, associated in 90% of the cases with
      a labral lesion. Tears involved the supraspinatus in 40 cases, the supraspinatus
      and the infraspinatus in 24 and the infraspinatus alone in three. Eight patients
      were free of tendon lesions at arthroscopy. There were no full thickness tears.
      The labrum had a meniscal (45%) or non-meniscal aspect (55%) and appeared normal
      (18%), fringed (38%) or fissured (52%). The very large majority of the labral
      fissures were found behind the biceps insertion. Fissures of the labrum were
      found in front of the biceps insertion in only three cases (slap lesion).
      Arthroscopy demonstrated glenoid damage (soft cartilage, fissure, abrasion,
      wear). The humeral head also exhibited lesions of the cartilage facing the
      insertion of the infraspinatus. At last follow-up (minimum > 2 years), eight
      patients were very satisfied, 22 were satisfied and 45 were disappointed. Twelve
      patients had resumed their sports activities at their former level with loaded
      arm movement and one patient had interrupted all sports activities. At last
      follow-up, 22 patient had undergone another surgical procedure: 20 derotation
      osteotomies of the humerus, one anterior stabilization, one acromioplasty.
      DISCUSSION: The notion of posterosuperior impingement is increasingly recognized
      as the cause of pain in thrower athletes. Loaded arm movements produce a
      physiological contact between the posteriorsuperior edge of the glenoid cavity
      and the deep aspect of the rotator cuff. Injury results from repeated loaded arm
      movements in throwers. In our series, all the patients had at least one lesion,
      either involving the cuff or the labrum. According to the Snyder classification,
      80% of the supraspinatus lesions were grade 1 or grade 2. We did not have any
      full thickness tears. All patients with a normal cuff were found to have a lesion
      of the posterosuperior labrum. At arthroscopy, dynamic assessment evidenced an
      impingement between the supraspinatus (or the infraspinatus) and the labrum or
      the bony edge of the glenoid cavity. Only three patients had a labral lesion
      anterior to the biceps insertion that could be considered a type 1 or 2 slap
      lesion. Unlike earlier reports by others, we had disappointing results after
      debridement: 60% of the patients were disappointed after the procedure and only
      40% were satisfied (22 patients) or very satisfied (8 patients). Patient
      satisfaction depended greatly on the level of sports activity attained after
      arthroscopy, the eight very satisfied patients had resumed their former level.
      None of the professional athletes or those competing at the international level
      were very satisfied with arthroscopic debridement. There was an inverse
      relationship between level of competition and patient satisfaction after
      debridement.

PMID- 11973532
TI  - [Bipolar arthroplasty in rotator cuff arthropathy: 13 cases].
AB  - PURPOSE OF THE STUDY: A series of 13 patients with an excentered osteoarthritis
      of the glenoid who underwent bipolar shoulder arthroplasty is reported. MATERIAL
      AND METHODS: The series included 13 patients treated in two centers between 1995
      and 1998. Mean age was 70 years (58-88). Constant's absolute score and Swanson's
      score were used for clinical assessment. The Hamada and Fukuda classification was
      used for the radiographic assessment. The follow-up radiography series included
      an AP view in the three rotation positions, an AP view in maximum abduction to
      assess intraprosthetic mobility, a lateral view (Lamy) and measurements of both
      humeri. Several measurements were made to assess humerus lateralization and
      glenoid wear: deltoid lever arm, lateral humeral displacement, distance between
      the lateral border of the coracoid and the center of the glenoid and the
      subacromial space. Mean preoperative Constant score was 23 points: pain 3 pts,
      activity 5 pts, motion 13 pts, force 2 pts. Mean preoperative Swanson score was
      11. Active anteflexion was 78 degrees, active abduction 68 degrees and passive
      external rotation 17 degrees. The Hamada and Fukuda classification was 9 grade 4
      and 4 grade 5. All patients had a full thickness unrepairable rotator cuff tear:
      three with 2 tendon tears, and 10 with 3 tendon tears. All patients were reviewed
      clinically and had a complete radiography series at last follow-up (mean 28
      months, range 7 - 56 months). RESULTS: At last follow-up, the mean absolute
      Constant score was 37 points: pain 10 pts, activity 9 pts, motion 14 pts, force 4
      pts. Mean Swanson score at last follow-up was 19 points. Mean active anteflexion
      was 69 degrees, active abduction was 63 degrees and passive external rotation was
      29 degrees. A satisfactory deltoid lever arm had been achieved compensating the
      glenoid wear by a greater lateral displacement of the humerus. At last follow-up,
      there were no cases of humeral loosening but three cases with important glenoid
      wear were observed after two years. Comparing the results obtained using small
      cups (40 and 44) with arthroplasties using large cups (48 and 52) showed a trend
      favoring small cups: Constant score 43 vs 32 points, Swanson score 21 versus 17
      points, anteflexion 72 degrees versus 66 degrees and passive external rotation 34
      degrees versus 26 degrees. DISCUSSION: Our results confirmed the efficacy of
      bipolar arthroplasty for pain relief, but the mobility outcome was less than
      satisfactory, excepting passive external rotation. It would appear to be
      preferable to use small cups. Comparing our results with data in the literature,
      particularly the better results for mobility using simple humeral prostheses,
      suggests that the principles of shoulder and hip arthroplasty concern different
      mechanisms: a sufficient deltoid lever arm must be achieved, but without
      overstretching the periarticular soft tissue (capsule, subcapsule, teres minor),
      and using a cup size close to the size of the healthy humeral head. Glenoid
      reaming should not be reserved only for asymmetrical glenoid wear in the
      horizontal plane. CONCLUSION: Our results suggest that bipolar arthroplasty for
      excentered osteoarthritis of the glenoid cavity is indicated for: stiffness in
      external rotation, major concentric wear in patients under 65 years of age, or
      asymmetric glenoid wear.

PMID- 11973533
TI  - [Shoulder fusion for sequelae secondary to brachial plexus palsy].
AB  - PURPOSE OF THE STUDY: We examined clinical and radiological outcome in fifteen
      patients who underwent shoulder fusion after brachial plexus palsy. MATERIAL AND
      METHODS: This retrospective analysis included 15 patients who underwent shoulder
      fusion between 1981 and 1997 for the treatment of sequelae secondary to brachial
      plexus palsy. There were 13 men and two women, mean age 24.6 years (range 18-33
      years). The right shoulder was fused in nine cases and the dominant shoulder in
      ten. There was one obstetric paralysis and one paralysis secondary to a cervical
      neurinoma. Eleven patients were motorcycle accident victims and two were
      automobile accident victims. The patients were installed in the lateral supine
      position with 30 degrees antepulsion and 60 degrees abduction, measured from the
      axillary axis of the scapula, and internal rotation. All patients had internal
      fixation by plate through a posterior approach. The same observer examined all
      the patients at last follow-up. Clinical and radiological findings were recorded
      and the position of the arthodesis was analyzed. RESULTS: There was one case of
      delaved fusion and one case of late humeral fracture. The arthrodesis position
      was abduction 52 degrees, internal rotation 20 degrees, flexion 20 degrees
      (means). Hand-mouth and hand-pocket movements were possible for all patients.
      Seven had no pain. Active motion was: 48 degrees abduction, 46 degrees
      antepulsion, 40 degrees internal rotation, 4.6 degrees external rotation, 23
      degrees retropulsion. For 13 patients, mean lifting force was 5.2 kg.

PMID- 11973534
TI  - [Femoral shaft fractures in the elderly treated by intramedullary nailing].
AB  - PURPOSE OF THE STUDY: Little work has been devoted to femoral shaft fractures in
      the elderly, contrasting with the data available for proximal neck or
      trochanteric fractures. The purpose of this study was to determine the
      epidemiological and clinical features of femoral shaft fractures in the elderly
      from a retrospective series of 58 patients who underwent locked intramedullary
      nailing procedures with Grosse and Kempf (GK) or long gamma (GL) nails. MATERIAL
      AND METHODS: The series included 38 women and 20 men, mean age 83.6 years, who
      suffered a fracture of the femoral diaphysis due to a fall at home (49
      fractures), a traffic accident (8 fractures) or a high-energy fall (1 fracture).
      Prior to the fracture, 10 patients had homolateral osteoarthritis and two had a
      contralateral hip arthroplasty. Twenty-six patients were in very good health, 19
      had a history of cardiovascular disease, 9 had diabetes and 12 suffered
      parkinsonian syndromes or dementia. The ASA score was I in 24, II in 23 and III
      in 11. The diaphyseal fracture was isolated in 31 cases and associated with
      trochanteric involvement in 27. The upper third of the femur was involved in 37
      cases, the middle third in 7 and the lower third in 14. Generally there was a
      simple spiroid subtrochanteric fracture line (36 cases), or a torsion wedge with
      or without a proximal extension. Mean delay to surgery was 1.9 days.
      Subtrochanteric fractures with a proximal line were stabilized with a GL (34
      nails) and diaphyseal fractures with a GK (24 nails). Mean duration of the
      procedure was 1.9 for GL and 2 hours for GK. In 22 cases (17 GL and 5 GK), a
      minimally invasive access was needed to achieve reduction or stabilization during
      reaming and insertion of complementary fixation (3 screw fixations, 7 cerclages).
      RESULTS: Six patients died before six months, 4 during the initial
      hospitalization. Twenty patients experienced general complications: 7 cases of
      phlebitis and 5 "end-of-life" syndromes. Infection occurred in 3 cases including
      one septic arthritis leading to a bedridden situation. A new fracture beyond the
      ends of the implant occurred in 2 others. The upright position was achieved
      within 31 days and total weight bearing within 69 days. Bone fusion was achieved
      at 4 months (mean). Six patients died between 6 and 12 months, giving a 20.6%
      mortality at 1 year. Clinical outcome at 12 months was available for 42 living
      patients: 21 were walking without assistance, 7 used a cane, 8 required crutches
      or another assistance device and 6 were bedridden. DISCUSSION: The general and
      functional prognosis of femoral shaft fractures in the elderly is the same as for
      proximal fractures. These diaphyseal fractures can be individualized due to their
      characteristic mechanical and anatomic features: composite fracture with a
      rotation element involving the distal portion of the trochanter and the proximal
      quarter of the diaphysis. Several types of ostheosynthesis have been proposed for
      fixation. Locked intramedullary nailing has been found to be effective despite
      the difficulty in reduction, especially for particularly proximal fractures.
      There is a risk of iterative fracture in the transition zones between the femoral
      component and the osteoporotic bone.

PMID- 11973535
TI  - [Secondary infection of joint implants: diagnostic criteria, treatment and
      prevention].
AB  - Peroperative contamination is the most frequent cause of infection after
      arthroplasty. For other cases of infection subsequent to bacteremia or a
      neighboring focus, it would be more appropriate to use the term "secondary"
      infections rather than hematogeneous infections. Arguments favoring secondary
      infection include long symptom-free interval between prosthesis implantation and
      the infectious episode, a causal germ not generally responsible for peroperative
      infection, presence of a distant infectious focus, positive blood culture, and a
      positive bacteriological sample from the prosthesis level showing the same strain
      as grown from the distant focus or blood samples. Both acute and chronic
      infections are observed, leading to prosthesis dysfunction. History taking
      generally identifies a neglected acute but transient episode. Search for a
      bacteriological diagnosis must be completed before initiating an antibiotic
      regimen. If detected very early, washing with open synovectomy and resection of
      suspicious tissue should be attempted in order to maintain the implant if
      possible. Local antibiotics have proven efficacy. Beyond a certain delay,
      treatment for chronic infection usually requires removing the prosthesis,
      cleaning the bone interface, and new arthroplasty delayed or not. Search for the
      portal must be undertaken early in order to initiate appropriate local treatment.
      The causal event may be any invasive procedure, with or without material
      implantation. The risk-benefit ratio for antibiotic prophylaxis remains to be
      determined.

PMID- 11973536
TI  - [A new locking nail for proximal humerus fractures: the Telegraph nail, technique
      and preliminary results].
AB  - We present a new nail, the telegraph nail, designed for the treatment of proximal
      fractures of the humerus. This nail has a new locking system providing a self
      stabilization of the cancelous screws inserted in small fragments. We discuss the
      surgical technique and present preliminary results. The anterolateral approach
      and nail insertion through the medial and well vascularized part of the cuff is
      described for simple fractures. With the cup and ball technique, this nail can
      also be used for complex fractures of the proximal humerus with three or four
      fragments and major displacement. With this method, the nail is inserted before
      reduction and locked in the distal humerus before fixation of the head and
      tuberosities around the head once the targeting device removed. We report results
      for the first 64 nails inserted in our unit during the first year (1998-1999).
      Outcome was assessed at 11 months mean follow-up using the Constant score.
      Outcome was favorable, including in patients with complex fractures involving 3
      or 4 separate displaced fragments. Besides providing an anatomically stable
      reconstruction, the telegraph nail has the advantage of allowing early
      mobilization of the shoulder joint. This method is a useful alternative to
      prosthetic reconstruction for traumatic fractures of the proximal humerus.

PMID- 11973537
TI  - [Leg length changes after upper tibial osteotomy: analysis of different
      preoperative planning methods].
AB  - PURPOSE OF THE STUDY: The amount of change in the length of the lower limb
      resulting from upper tibial osteotomy depends on the type of osteotomy performed,
      the preoperative length of the limb, the degree of preoperative deformity and the
      amount of correction obtained. Wedge resection, for example, removes bone tissue
      and can lead to shortening. Inversely, a lengthening effect may result from
      correction of deformity. The purpose of this article was to present an analysis
      of the differences between different types of osteotomies and compare their
      effect on leg length. METHODS: Change in length of the lower limb was studied
      with a mathematical analysis in opening wedge osteotomy, closing wedge osteotomy,
      and dome osteotomy. Leg length was calculated for several preoperative deformity
      angles of the entire limb (hip-knee-ankle angle) and several values of planned
      correction. RESULTS: The theoretical mathematical model demonstrated that the
      greatest changes in leg length are obtained with opening wedge osteotomy,
      followed by dome, then closing wedge osteotomy. Tables were established showing
      calculated change in leg length. Tracings on radiographs or CT scans used to
      measure these changes are explained. Methods applicable in case of flexion
      contracture of the knee are presented. DISCUSSION AND CONCLUSION: Once the
      initial question regarding length changes is posed, many of the points become
      evident on image tracings. This work points out how quickly tables can be used to
      recognize significant differences in leg length changes produced by different
      osteotomies.

PMID- 11973538
TI  - [Posterior interosseous nerve palsy].
AB  - We report a case of radial palsy of the Frohse arcade type with complete motor
      deficit due to compression of the posterior interosseous nerve by a fibrous bands
      in the radial tunnel proximal to the arcade. Simple neurolysis of the posterior
      interosseous nerve with section of the compressing fibrous bands allowed complete
      recovery of the motor deficit. We discuss the surgical technique based on our
      experience with this case and earlier reports in the literature.

PMID- 11973539
TI  - [Multifocal bony hemangioendothelioma: a case report].
AB  - Hemangioendothelioma is a rare tumor (0.5% of primary malignant bone tumors)
      generally found in long bones and tarsal bones. We report a case in a 67-year-old
      man who underwent surgery in 1987 for a tumor of the left ankle. He again
      consulted in 1998 for pain in the left knee. Standard x-rays of the left lower
      limb evidenced multiple partitioned bone defects with cortical lysis in the
      femoral condyle, the upper and lower portions of the tibia and the talus.
      Computed tomography showed a lytic image of the lower femoral and superior tibial
      epiphysis without cortical or soft tissue involvement. Laboratory findings were
      normal. Pathology examination of a biopsy specimen led to the diagnosis of grade
      I multifocal bony hemangioendothelioma of the medial femoral condyle and the
      medial upper tibial facet of the left knee. Search for extension was negative.
      Curettage followed by cement filling of all tumor sites and postoperative
      radiotherapy were successful. No recurrence has been observed 3 years later. The
      histological polymorphism of hemangioendotheliomas leads to varying therapeutic
      management schemes.

PMID- 11973540
TI  - [Contribution of systematic culture of drainage fluids in Altemeier class 1 and 2
      procedures].
AB  - PURPOSE OF THE STUDY: We conducted a prospective study to determine the
      therapeutic impact of systematic culture of suction drainage collections in
      Altemeier class I and II procedures. MATERIALS AND METHODS: We examined the
      following questions: how many microbiologically positive samples and infections
      of the operative site were present in the included patients? for positive cases,
      what was the antibiotic prescription (excluding antibiotic prophylaxy protocols
      planned before surgery for cleaning)? if the sample was positive in a patient
      with no clinical infection, what antibiotics were prescribed? RESULTS: A total of
      1039 samples were collected in 470 patients undergoing Altemeier class I and II
      procedures. One hundred five cultures were positive in 34 patients who had
      undergone major surgery. There were 11 postoperative infections during the study
      period. Mean delay to diagnosis of infection was 19.5 days. Only one infected
      patient with positive drainage samples developed an infection on the 7(th) day;
      the causal germ was different from that identified in the drainage collection.
      Only one of the patients with a positive drainage sample was given antibiotics,
      but this treatment was initiated at peroperative reception of the laboratory
      results. DISCUSSION: Our findings demonstrate that systematic samples of drainage
      collections make no contribution to therapeutic decision making in patients
      undergoing class I and II surgery.

PMID- 11973541
TI  - [Unilateral forearm agenesis and prosthesis].
AB  - PURPOSE OF THE STUDY: Antebrachial agenesis is a congenital deformity which is
      not invalidating for the children who have a level of independence comparable to
      that of other children of the same age. Although the appropriateness of a
      prosthesis is rarely questioned by healthcarers, it is clear that it is the
      healthcarers' own representation of this condition (their knowledge of the
      deformity and of the prosthesis proposed) that leads to the indication. The
      purpose of this study was to better understand the respective representations of
      unilateral antebrachial agenesis to help determine appropriate health care
      proposals. MATERIAL AND METHODS: An intensive survey using semi-directive
      interviews was conducted in 16 families. Group interviews with three healthcare
      teams were then conducted. RESULTS: Three leading topics appeared: worry about
      the social integration of the child, a paradoxical representation of the child
      perceived as independent but handicapped, and a largely negative image of the
      prosthesis. There was a rather important difference in the representations
      formulated by the parents and by the healthcarers. DISCUSSION: The discussion
      focused on awareness of the narcissistic content of the expectations and the
      plastic and functional implications of prosthesis fitting, perceived differently
      by parents and healthcarers. CONCLUSION: The nature of the expected result
      involves a change in the representation of the child more than a change in the
      child's body, a concept which in itself is not a true objective of healthcare.
      Taken the understandably difficult position of healthcarers, it might be useful
      to propose a different scheme for the first consultation.

PMID- 11973542
TI  - [Lunocapitate shortening arthrodesis after scaphoid and triquetrum resection:
      treatment of Watson stage III advanced scaphoid periarthrosis].
AB  - PURPOSE OF THE STUDY: Between 1993 and 2000, 16 patients with scaphoid
      periarthrosis (Watson stage III) were treated by lunocapitate shortening
      arthrodesis after resection of the scaphoid and triquetrum. These patients were
      reviewed to evaluate outcome. MATERIAL AND METHODS: Thirteen patients had
      antecedent trauma with scaphoid nonunion (SNAC, n=9) or scapholunate advanced
      collapse (SLAC, n=4). The remaining three patients had chondrocalcinosis.
      RESULTS: Clinical and radiological results were encouraging at a mean follow-up
      of 3 years (1-7 years). Fourteen patients were very satisfied and two experienced
      partial improvement. Persistent pain relief as well as 11% improved muscle power
      was achieved. Mean improvement of joint motion was 12 degrees. DISCUSSION: This
      technique has shown better global results than 4-corner arthrodesis. It can be
      applied if capitate arthrodesis is performed. Results are comparable to those of
      proximal row carpectomy.

PMID- 11973543
TI  - [Arthroscopic reconstruction of the anterior cruciate ligament].
AB  - PURPOSE OF THE STUDY: We report a retrospective series of 83 patients (86 knees)
      who underwent reconstruction surgery for chronic anterior knee laxity. The
      purpose of this study was to analyze mid-term results and assess prognosis
      factors. MATERIAL AND METHODS: All patients underwent artrhoscopic reconstruction
      of the anterior cruciate ligament using a central one-third patellar tendon
      graft. Full follow-up data were available for 51 patients (52 knees) and partial
      data for 24 others (25 knees). Eight patients (9 knees) were lost to follow-up.
      The IKDC criteria were used to analyze outcome at a mean 6 years post-surgery.
      RESULTS: Graft failure was observed in 5 knees and a graft tears after a new
      sprain was seen at 3 years. The patients were satisfied or very satisfied in
      88.5% of the cases. The Trillat-Lachman test revealed a persistent dampened brake
      in 5 knees and a frank click in 4 (7.7%). Complete movement was recovered in all
      knees excepting 2 exhibiting persistent flexion. Residual laxity (active Lachman
      test) was 5 mm in 81.5% of the cases, between 6 and 10 mm in 17%, and greater
      than 10 mm in only 1 case (2.5%). IKDC scores were A=25%, B=50%, C=21% and D=4%.
      Forty-two patients (61%) returned to their sports activities and 9 of the 12 high
      level athletes resumed competition at the same level as preoperatively.
      Arthroscopy enabled a well- or very well-positioned femoral tunnel in 88% of the
      cases, conditioning final IKDC outcome (p<0.02). There was a correlation between
      the meniscal status and residual laxity. DISCUSSION: This study demonstrated a
      high proportion (21%) of patients with an incomplete repair (21% IKDC class C)
      with a residual laxity greater than 5 mm and a late hard brake. Simple patellar
      tendon graft provided insufficient repair of the anterior cruciate ligament. The
      subjective outcome was better than the objective outcome since 88.5% of the
      patients were satisfied or very satisfied (patients seen at last follow-up or
      contacted by telephone). Good objective outcome was correlated with good femoral
      position of the transplant and preservation of the meniscus. Failures were
      explained by poor position of the transplant, long-standing laxity, and renewal
      of sports activities too early. CONCLUSION: Arthroscopic repair of the anterior
      cruciate ligament is a reliable procedure, but as failures are observed,
      indications should take into consideration the type of laxity and the status of
      the meniscus. For unique anterior laxity, the central one-third patellar tendon
      graft gives good results. For advanced anterior laxity, augmentation with an
      extra-articular lateral tenodesis would be necessary.

PMID- 11973544
TI  - [Anterior cruciate ligament reconstruction: patellar tendon autograft versus four
      strand hamstring tendon autografts. A comparative study at one year follow-up].
AB  - PURPOSE OF THE STUDY: The purpose of our study was to compare outcome at one year
      after anterior cruciate ligament reconstruction for chronic laxity using the
      patellar tendon autograft or four-strand hamstring tendon autografts. MATERIAL
      AND METHOD: This non-randomized study included 129 consecutive patients operated
      on between October 1996 and September 1998. Ninety patients were available for
      assessment at one year: 50 in the patellar tendon group and 40 in the hamstring
      tendon group. The two groups were comparable for all criteria except sex. A
      single operator assessed all patients using the IKDC 93 chart. Laxity was
      measured by comparison with the healthy knee using the KT1000 at maximal manual
      tension. Preoperative laxity was 8.0 +/- 3.0 mm in the patellar tendon group and
      7.6 +/- 3.0 in the hamstring tendon group. All ligamentoplasties were performed
      arthroscopically using a blind femoral tunnel. The patellar tendon was fixed with
      two metallic interference screws and the four-strand hamstring autografts with
      two different methods: an RCI(R) interference screw or a cortical system
      associating a femoral Endobutton(R) and tibial fixation with a bicortical tibial
      screw. Lateral tendonesis was performed with the fascia lata in 60% of the
      patients in the patellar tendon group and in 45% of those in the hamstring tendon
      group. Rehabilitation exercises were initiated early and were the same in the two
      groups. RESULTS: Overall results were satisfactory in more than 80% of the
      patients in both groups. The final IKDC score was significantly better in the
      patellar tendon group and subjective patient satisfaction was better in the
      hamstrings group. Residual pain was significantly less pronounced in the
      hamstrings tendon group (p=0.004). Laxity was improved significantly better in
      the patellar tendon group: average residual laxity=2.7 +/- 2.1 mm versus 4.5 +/-
      2.8 mm (p=0.03) in the hamstrings tendon group; hard stop at the Lachman test in
      96% of the patellar tendon group and 78% in the hamstrings tendon group
      (p=0.007). Residual laxity was significantly less pronounced in the women in the
      patellar tendon group. There was no significant difference in laxity by type of
      fixation in the hamstrings tendon group. Recovery in terms of level of activity
      and type of sport was the same in the two groups. DISCUSSION: These two surgical
      techniques provide good functional outcome at one year with better control of
      laxity with patellar tendon autografts and better relief of pain with four-strand
      hamstrings autografts. Longer follow-up would be useful to assess laxity long
      after hamstring reconstruction. We compared the type of transplant and the
      fixation method together as a single unity, but progress in four-strand hamstring
      autograft fixation will certainly allow even more optimal results and improved
      correction of laxity. In our opinion, the patellar tendon autograft remains the
      gold standard for high-performance athletes practicing a contact-pivot sport, but
      both types of ACL reconstruction are most useful. We select patients for four
      strand hamstring tendon reconstruction as a function of age, sex, and type of
      sports activities.

PMID- 11973545
TI  - [Ligamentoplasty of the anterior cruciate ligament after 40 years: a series of 41
      patients].
AB  - PURPOSE OF THE STUDY: Ligamentoplasty for tears of the anterior cruciate ligament
      (ACL) is generally thought to be unreliable after the age of 40 years. The
      purpose of this retrospective analysis was to assess the five-year outcome after
      ACL plasty in patients aged over 40 at the time of surgery. MATERIAL AND METHODS:
      Between 1990 and 1997, 41 patients aged 44.5 +/- 4.5 years (28 men, 25 right
      side) underwent intra-articular reconstruction of the ACL. Clinical and
      radiological assessment using the IKDC criteria was obtained at a mean 62 months
      postoperatively using manual instrumental measurements with KT-1000. The
      indication for reconstruction was instability in daily life activities for 40
      patients and difficulties encountered in sports activities in one; there were
      three cases of remodeling. Arthroscopy was used in all cases to perform a
      patellar tendon graft (bone-tendon-bone in 30 cases associated with extra
      articular lateral reinforcement in eleven). RESULTS: There were no significant
      complications. Among 12 patients who initially participated in competition
      sports, seven were able to resume their activity at their former level. At last
      follow-up, global IKDC score was A for 12, B for 25, and C for three and D for
      one. All patients scored C or D had a poor IKDC symptom score, basically because
      of pain. Motion was not modified. The IKDC radiology score was A for 25, B for 15
      and C for one, but the three cases of remodeling did not progress. Prognostic
      factors for overall IKDC result were: age of the patient at the time of
      reconstruction (under 45 years), and the delay to surgery for accident victims
      (less than one year). The following criteria had no effect at last follow-up:
      gender, sport practiced, type of initial laxity (anterior alone or global
      anterior), presence of meniscal damage, preservation of the medial and/or lateral
      meniscus, chondral injury observed peroperatively, and use of a lateral
      reinforcement. Radiographic remodeling observed in this group of 41 patients was
      related to delay from accident to surgery (p=0.0007) and preservation of the
      medial meniscus (p=0.03). Age, gender, type of activity before surgery, degree of
      initial and residual laxity had no statistically significant effect on
      remodeling. CONCLUSION: Age over 40 years is not a contraindication for
      arthroscopic free patellar tendon graft for the treatment of chronic anterior
      laxity. Using rigorous preoperative assessment criteria (delay from accident to
      surgery, absence of joint space narrowing on the AP and lateral view before
      intervention, symptomatic instability in daily life activities and motivated
      patient) this type of procedure can be performed safely and provides good
      functional outcome at five years. The current follow-up is insufficient to judge
      potential joint degradation. Age is not a contraindication if certain precautions
      are taken.

PMID- 11973546
TI  - [Seventeen year outcome after anterior cruciate ligament reconstruction with a
      intact or repaired medial meniscus].
AB  - PURPOSE OF THE STUDY: Ten-year outcome of anterior cruciate ligament (ACL)
      reconstruction was previously reported (1992-1993) for 148 patients who had ACL
      free grafts associated with extra-articular tenodesis. In this retrospective
      study, we examined the functional and radiological changes observed 17 years
      after surgery in patients whose menisci were intact or repaired at ACL
      reconstruction (46 cases). These patients were operated on between 1978 and 1983.
      MATERIAL AND METHODS: Between January and April 1999, 28 patients were reviewed
      clinically and radiographically. Nine other patients responded to a questionnaire
      and three of them sent their x-rays. Two patients had died since the last review
      and 7 were lost to follow-up. Mean age at follow-up was 41 years. The IKDC
      classification was A 18.5%, B 51%, C 22.2%, D 7.4% in 26 patients reviewed with
      the passive radiological Lachman. At subjective analysis (n=37), 70% of the
      patients were very satisfied and 27% were satisfied. At radiological analysis
      (n=31), the AP or lateral single-limb stance views and the AP two-limb weight
      bearing views at 45% flexion demonstrated preosteoarthritis in 22% and
      osteoarthritis in 3%. Residual anterior tibial translation was the same at 11
      years and 17 years follow-up. DISCUSSION: This study clearly demonstrates that
      ACL reconstruction associated with extra-articular tenodesis can provide good
      functional and radiological results at 17 years mean follow-up for patients with
      preserved (sound or sutured) menisci. The status of the medial meniscus at long
      term follow-up appears to be the key feature determining the low rate of
      degenerative changes.

PMID- 11973547
TI  - [Arthroscopic release for knee joint stiffness after total knee arthroplasty].
AB  - PURPOSE OF THE STUDY: Overall, the results of total knee replacement surgery are
      quite excellent, both with regard to pain and range of motion. Pain relief is
      obtained in more than 95% of the cases and more than 90% of the patients are able
      to bend their knee over 90 degrees. Nevertheless, in a small number of cases,
      stiffness can be an impairment. MATERIAL AND METHODS: Between 1992 and 1998, six
      arthroscopic releases were performed on six patients who had undergone total knee
      replacement. The six patients suffered from unacceptable stiffness. The average
      age of the patients was 68.5 years, and the time elapsed from implantation to
      arthroscopy averaged 24 months (6 months to 6 years). Average follow-up was 19
      months (6 to 96 months). The six stiff knees were treated with arthroscopic
      debridement of fibrous tissue around the patella and quadriceps tendon (to
      improve extension) and by arthroscopic division of the medial and lateral
      retinacula (to address flexion). A gentle manipulation was carried out following
      lysis of adhesions, using a slight pressure on the tubercle to avoid fractures
      and disruptions of the extensor mechanisms. Postoperatively, immediate physical
      therapy was performed including continuous passive motion and active muscular
      contraction. Early weight bearing was allowed. RESULTS: The average flexion
      contracture decreased from 9 degrees prior to arthroscopy to 2.5 degrees at last
      follow-up. Average flexion increased from 70 to 100 degrees. Maximal improvement
      was obtained at three months. DISCUSSION: Results were found to be quite good,
      with a final knee score of 93 and a function score of 92 (following International
      Knee Society scoring). CONCLUSION: Arthroscopic release following total knee
      replacement complicated by joint stiffness provides a satisfactory increase in
      range of motion.

PMID- 11973548
TI  - [Talar neck fracture: 9-year follow-up of 40 cases].
AB  - PURPOSE OF THE STUDY: Complication rate is high after talar neck fractures.
      Avascular osteonecrosis and post-traumatic joint degeneration could be avoided by
      proper management. We analyzed long-term outcome in a series of 40 talar neck
      fractures treated in our unit from 1979 to 1995. MATERIAL AND METHODS: Mean
      follow-up was 9 years. Orthopedic and surgical management by Hawkins
      classification group was, respectively, type I=10 (7 and 3), type II=17 (3 and
      14), type III=11 (1 and 10) and type IV=2 (both surgery). Two patients had
      bilateral fractures and 7 fractures were open. Among the 29 fractures treated
      surgically, the anteromedial approach was used for open reduction and fixation
      for 18. A dual approach was needed for 1 patient with a type III fracture.
      Fixation was achieved with cancelous screws for 17/29 fractures including 3
      fluted screw fixations, cortical screws for 9, K-wires for 2 and staples for 1.
      RESULTS: According to the AOFAS classification, mean function score at last
      follow-up was 94.4/100 for type I, 78.5 for type II, 69.5 for type III, and 57.5
      for type IV. Signs of osteoarthritis were observed in 68% of the cases with
      clinical expression in 9 out of 10 cases. DISCUSSION: The results show that
      conservative treatment is indicated for type I fractures while open reduction and
      fixation should be used for types II, III, and IV. Subsequent joint degeneration
      was correlated with the type of fracture and clearly influenced functional
      outcome. In our long-term follow-up, we only had two cases of osteonecrosis which
      finally necessitated arthrodesis. This low rate would be related to the fact that
      most of the patients were able to avoid weight bearing for several months.

PMID- 11973549
TI  - [Medial approaches to the distal humerus for fracture fixation].
AB  - PURPOSE OF THE STUDY: We report our experience with the medial and medioposterior
      approaches to the humeral diaphysis for plate fixation of the proximal humerus.
      MATERIAL AND METHODS: Fifteen patients were treated for shaft fracture (n=13) or
      nonunion (n=2) of the distal third of the humerus without radial nerve
      involvement. The medial approach was performed in the supine position and the
      medioposterior approach in the prone position. Bone healing was achieved in all
      cases. Three patients experienced sensorial irritation in the territory of the
      median nerve after the medial approach; one case did not regress. There were no
      complications with the medioposterior approach. DISCUSSION: Dissection of the
      radial nerve can be avoided with these two approaches which also have a cosmetic
      advantage. The medioposterior approach appears to be preferable because of the
      comfortable operative position and the absence of risk for the median nerve. Both
      approaches are however contraindicated if there is preoperative involvement of
      the radial nerve.

PMID- 11973550
TI  - [Synovial cyst of the intercondylar fossa of the knee: three symptomatic cases
      and a review of the literature].
AB  - Synovial cyst of the intercondylar fossa of the knee or cyst of the "cruciate
      tentorium" is an uncommon finding. Most of the reports in the literature were
      made after the advent of magnetic resonance imaging. Most cysts are asymptomatic
      and discovered fortuitously. We report our experience with three cases of
      symptomatic cysts, describing the diagnostic and therapeutic approaches used.
      Clinical manifestations of symptomatic cysts are variable and non-specific. Pain
      is commonly observed with limitation of knee amplitudes. If their is no other
      suspected meniscal or osteochondral disease after clinical and MRI assessment,
      surgical treatment is only indicated in case of functional impairment. Medical
      care may be sufficient in certain cases, associating puncture and infiltration.
      In others surgical treatment, generally via an arthroscopic approach, is needed.

PMID- 11973551
TI  - [Periosteal Ewing's sarcoma].
AB  - Periosteal Ewing's sarcoma is a histologically typical Ewing's sarcoma arising in
      the periosteum with no involvement of the medullary canal or cancellous bone. We
      describe four cases in our experience and review the literature, recalling the
      usual computed tomography diagnostic criteria and the therapeutic consequences.
      Prognosis of periosteal Ewing's sarcoma is generally better than for ordinary
      Ewing's sarcoma. In order to avoid inoculating the canal, the operator must
      strictly avoid perforating the cortical during the biopsy. At surgical resection,
      cortical resection can be partial maintaining a continuous diaphysis; this should
      be examined as a possibility for young patients in order to avoid the problems
      encountered with massive reconstruction followed by chemotherapy.

PMID- 11973552
TI  - [Hydatid cyst of the thigh: three cases].
AB  - Three patients presented a benign soft tissue mass in the thigh muscles.
      Ultrasonography provided the diagnosis of hydatid cyst. Total pericystecomy was
      performed in all cases with no recurrence at 8 months, 3 years and 4 years. We
      point out the importance of preoperative diagnosis and the need for radical
      excision to avoid recurrence.

PMID- 11973554
TI  - Detection of Loxosceles species venom in dermal lesions: a comparison of 4 venom
      recovery methods.
AB  - STUDY OBJECTIVE: Loxosceles species spider envenomations may produce necrotic,
      disfiguring dermal inflammatory lesions resembling neutrophilic dermatoses. With
      definitive treatment options lacking, clinicians are reluctant to obtain invasive
      biopsy specimens for diagnostic analysis. We compared less invasive venom
      collection methods and determined the time limit after inoculation for feasible
      venom recovery in an animal model. METHODS: Nine New Zealand rabbits were
      randomized to 1 of 3 groups (n=3). Groups 1 and 2 were inoculated intradermally
      with 3 microg of L reclusa venom at 5 inoculation sites per rabbit. Albumin (3
      microg) was injected intradermally in each rabbit as a negative control. Hair
      (group 1) and aspirate samples (group 2) were collected (1 time per site) over a
      1-week period after inoculation. Group 3 was inoculated with 3 microg of
      Loxosceles species venom on 1 flank and 3 microg of albumin on the opposite
      flank. Daily serum specimens were collected over a 7-day period. On day 7, dermal
      punch biopsy specimens were taken from the venom and control inoculation sites.
      Hair, aspirate, biopsy, and serum specimens were assayed for venom by using an
      enzyme-linked immunosorbent assay. A generalized linear model was fit with the
      generalized estimating equation method to estimate the mean differences between
      groups. RESULTS: Venom was detected in hair, aspirate, and biopsy specimens on
      all days of the study period. Hair samples yielded venom recovery on day 1
      (median 0.062 ng/100 microL; mean difference 0.054 ng/100 microL; 95% confidence
      interval [CI] 0.048 to 0.059) through day 7 (median 0.020 ng/100 microL; mean
      difference 0.020 ng/100 microL; 95% CI 0.013 to 0.027). Aspirates were positive
      for venom recovery on day 1 (median 0.275 ng/100 microL; mean difference 0.231
      ng/100 microL; 95% CI 0.192 to 0.271) through day 7 (median 0.0 ng/100 microL;
      mean difference 0.032 ng/100 microL; 95% CI -0.18 to 0.078). The highest venom
      yield was from the biopsy specimens (median 1.75 ng/100 microL; mean difference
      0.041 ng/100 microL; 95% CI 0.033 to 0.027). Venom was undetectable in all serum
      samples. CONCLUSION: Loxosceles species venom is detectable in hair, aspirate,
      and dermal biopsy specimens at least 7 days after venom inoculation and
      undetectable in serum by using the rabbit model.

PMID- 11973553
TI  - A new assay for the detection of Loxosceles species (brown recluse) spider venom.
AB  - STUDY OBJECTIVE: Dermal lesions from unrelated arthropod species and medical
      causes appear similar to Loxosceles species (brown recluse spider) bites. This
      may result in delayed diagnosis and treatment. We developed a sensitive
      Loxosceles species venom enzyme-linked immunosorbent assay (ELISA) and
      characterized the specificity of the assay by evaluating antigenic cross
      reactivity from a variety of North American arthropod venoms. METHODS: North
      American arthropod (14 spiders, 2 scorpions, and 1 bee) venoms were studied.
      Three venom amounts (diluted in 100 microL of ELISA buffer) were assayed: 16,000
      ng, 2,000 ng, and 40 ng. The latter quantity was selected because this is the
      observed maximum amount of venom we detect when inoculating dermis with amounts
      likely to be deposited by a spider bite. The larger venom amounts are
      overwhelming quantities designed to test the limits of the assay for arthropod
      venom cross-reactivity. Similar amounts of Loxosceles species venom and bovine
      albumin served as positive and negative controls, respectively. RESULTS: At the
      lowest amount of venom tested (40 ng), the ELISA detected only the Loxosceles
      species positive control. When 2,000 ng was assayed, only Scytodes fusca and
      Kukulcania hibernalis arachnid venoms (in addition to Loxosceles species) cross
      reacted to the assay. Finally, at 16,000 ng, the ELISA assay modestly detected
      Diguetia canities, Heteropoda venatoria, Tegenaria agrestis, Plectreurys tristes,
      Dolomedes tenebrosus, and Hadrurus arizonensis arachnid venoms. CONCLUSION: Cross
      reactivity was observed in 8 of 17 North American arthropod venoms when large
      venom amounts were assayed with a Loxosceles species ELISA. By using a relevant
      quantity of venom, 40 ng, the assay was specific for Loxosceles species venom.
      The venom specificity of the ELISA may allow clinical application in Loxosceles
      species endemic regions of North America.

PMID- 11973555
TI  - Use of out-of-hospital variables to predict severity of injury in pediatric
      patients involved in motor vehicle crashes.
AB  - STUDY OBJECTIVE: We sought to create a clinical decision rule, on the basis of
      variables available to out-of-hospital personnel, that could be used to
      accurately predict severe injury in pediatric patients involved in motor vehicle
      crashes as occupants. METHODS: We analyzed the National Automotive Sampling
      System database, a national probability sample, using pediatric patients up to 15
      years old (occupants only) involved in motor vehicle crashes from January 1993 to
      December 1999. The National Automotive Sampling System database includes patients
      from regions throughout the country, weighted to represent a nationwide sample.
      Twelve out-of-hospital variables were used in classification and regression tree
      analysis to create a decision rule separating children with severe injuries
      (Injury Severity Score [ISS] > or =16) from those with minor injuries (ISS < 16).
      Misclassification costs and complexity parameters were selected to yield a
      decision tree with appropriate sensitivity and specificity for the identification
      of severely injured patients, while also being simple and practical for out-of
      hospital use. Probability weights were used throughout the analysis to account
      for the sampling design and sampling weights. RESULTS: Using a sample size of
      8,392 children, we constructed a decision rule using 3 out-of-hospital variables
      (Glasgow Coma Scale score, passenger space intrusion > or =6 in [> or =15 cm],
      and restraint use) to predict those patients with an ISS of 16 or more. Internal
      cross-validation was used to determine the sensitivity and specificity, yielding
      values of 92% and 73%, respectively, for the prediction of patients with an ISS
      of 16 or more. CONCLUSION: Out-of-hospital variables available to field personnel
      could be used to effectively triage pediatric motor vehicle crash patients using
      the decision rule developed here. Prospective trials would be needed to test this
      decision rule in actual use.

PMID- 11973556
TI  - A clinical decision rule for identifying children with thoracic injuries after
      blunt torso trauma.
AB  - STUDY OBJECTIVE: We sought to determine the prevalence of thoracic injuries in
      children sustaining blunt torso trauma and to develop a clinical prediction rule
      to identify children with these injuries. METHODS: We prospectively enrolled
      pediatric patients (<16 years) who presented to the emergency department of a
      Level I trauma center with blunt torso trauma and underwent chest radiography.
      Clinical findings were recorded in a standardized fashion by the ED faculty
      physician. Thoracic injuries included the following: pulmonary contusion,
      hemothorax, pneumothorax, pneumomediastinum, tracheal-bronchial disruption,
      aortic injury, hemopericardium, pneumopericardium, cardiac contusion, rib
      fracture, sternal fracture, or any injury to the diaphragm. Multiple logistic
      regression and recursive partitioning analyses were performed to generate a
      clinical prediction rule for identifying children with these injuries. RESULTS:
      Nine hundred eighty-six patients with a mean age of 8.3+/-4.8 years were
      enrolled. Eighty (8.1%; 95% confidence interval [CI] 6.5% to 10.0%) patients
      sustained thoracic injuries. Multiple logistic regression and recursive
      partitioning analyses identified the following predictors of thoracic injuries:
      low systolic blood pressure (14% with injury versus 2% without injury; adjusted
      odds ratio [OR] 4.6), elevated age-adjusted respiratory rate (51% versus 16%;
      adjusted OR 2.9), abnormal results on examination of the thorax (68% versus 36%;
      adjusted OR 3.6), abnormal chest auscultation findings (14% versus 1%; adjusted
      OR 8.6), femur fracture (13% versus 5%; adjusted OR 2.2), and a Glasgow Coma
      Scale (GCS) score of less than 15 (61% versus 26%; adjusted OR 3.3). Seventy
      eight (98%; 95% CI 91% to 100%) of the 80 patients with thoracic injuries had at
      least 1 of these predictive factors. Three hundred thirty-six (37%) children had
      none of these predictive factors, including 2 (0.6%; 95% CI 0.1% to 2.1%) with
      thoracic injuries. These 2 injuries, however, did not require any intervention.
      CONCLUSION: Predictors of thoracic injury in children sustaining blunt torso
      trauma include low systolic blood pressure, elevated respiratory rate, abnormal
      results on thoracic examination, abnormal chest auscultation findings, femur
      fracture, and a GCS score of less than 15. These predictors can be used to create
      a sensible clinical decision rule for the identification of children with
      thoracic injuries.

PMID- 11973557
TI  - Identification of children with intra-abdominal injuries after blunt trauma.
AB  - STUDY OBJECTIVE: We sought to determine the utility of laboratory testing after
      adjusting for physical examination findings in the identification of children
      with intra-abdominal injuries after blunt trauma. METHODS: The study was a
      prospective observational series of children younger than 16 years old who
      sustained blunt trauma and were at risk for intra-abdominal injuries during a
      2(1/2)-year period at an urban Level I trauma center. Patients were examined by
      faculty emergency physicians and underwent standardized laboratory testing.
      Clinical and laboratory findings were recorded on a standardized data sheet.
      Intra-abdominal injury was considered present if an injury was documented to the
      spleen, liver, pancreas, kidney, adrenal glands, or gastrointestinal tract. We
      performed multiple logistic regression and binary recursive partitioning analyses
      to identify which physical examination findings and laboratory variables were
      independently associated with intra-abdominal injury. RESULTS: Of 1,095 enrolled
      patients, 107 (10%, 95% confidence interval [CI] 8% to 12%) had intra-abdominal
      injuries. The mean age was 8.4+/-4.8 years. From both analyses, we identified 6
      findings associated with intra-abdominal injury: low systolic blood pressure
      (adjusted odds ratio [OR] 4.1; 95% CI 1.1 to 15.2), abdominal tenderness
      (adjusted OR 5.8; 95% CI 3.2 to 10.4), femur fracture (adjusted OR 1.3; 95% CI
      0.5 to 3.7), serum aspartate aminotransferase concentration more than 200 U/L or
      serum alanine aminotransferase concentration more than 125 U/L (adjusted OR 17.4;
      95% CI 9.4 to 32.1), urinalysis with more than 5 RBCs per high-powered field
      (adjusted OR 4.8; 95% CI 2.7 to 8.4), and an initial hematocrit of less than 30%
      (adjusted OR 2.6; 95% CI 0.9 to 7.5). CONCLUSION: After adjusting for physical
      examination findings, laboratory testing contributes significantly to the
      identification of children with intra-abdominal injuries after blunt trauma.

PMID- 11973558
TI  - Report of the task force on residency training information (2001-2002), American
      Board of Emergency Medicine.
AB  - The American Board of Emergency Medicine gathers extensive background information
      on emergency medicine residents and the programs in which they train. We present
      the fifth annual report on the status of US emergency medicine residency programs

PMID- 11973559
TI  - Cryptogenic rabies, bats, and the question of aerosol transmission.
AB  - Human rabies is rare in the United States; however, an estimated 40,000 patients
      receive rabies postexposure prophylaxis each year. Misconceptions about the
      transmission of rabies are plentiful, particularly regarding bats. Most cases of
      human rabies caused by bat variants have no definitive history of animal bite.
      Three hypotheses are proposed and reviewed for the transmission of rabies from
      bats to human beings. They include nonbite transmission (including aerosol
      transmission), the alternate host hypothesis (an intermediate animal host that
      acquires rabies from a bat and then transmits rabies to human beings), and
      minimized or unrecognized bat bites. Nonbite transmission of rabies is very rare,
      and aerosol transmission has never been well documented in the natural
      environment. The known pathogenesis of rabies and available data suggest that all
      or nearly all cases of human rabies attributable to bats were transmitted by bat
      bites that were minimized or unrecognized by the patients.

PMID- 11973560
TI  - Is pediatric trauma really a surgical disease?

PMID- 11973561
TI  - Dogs, cats, raccoons, and bats: where is the real risk for rabies?

PMID- 11973562
TI  - The diagnosis of brown recluse spider bite is overused for dermonecrotic wounds
      of uncertain etiology.

PMID- 11973563
TI  - How to find evidence when you need it, part 3: a clinician's guide to MEDLINE:
      tricks and special skills.

PMID- 11973564
TI  - Evidence-based emergency medicine/systematic review abstract. Use of the
      neuraminidase inhibitor class of antiviral drugs for treatment of healthy adults
      with an acute influenza-like illness.

PMID- 11973565
TI  - Evidence-based emergency medicine/systematic review abstract. Use of low
      molecular weight heparins in patients with acute venous thromboembolism.

PMID- 11973566
TI  - Lyme disease masquerading as brown recluse spider bite.
AB  - We report a case of Lyme disease with clinical features resembling those
      described from brown recluse spider bites. The most striking manifestation was a
      necrotic skin wound. Brown recluse spider bites may be overdiagnosed in some
      geographic regions. Tick bite and infection with Borrelia burgdorferi should be
      considered in the differential diagnosis of necrotic arachnidism in regions
      endemic for Lyme disease.

PMID- 11973568
TI  - Coccidioidomycosis in workers at an archeologic site-Dinosaur National Monument,
      Utah, June-July 2001.

PMID- 11973567
TI  - A call for critical care training of emergency physicians.

PMID- 11973569
TI  - Caring for the survivors.

PMID- 11973570
TI  - A time to embrace...(Ecclesiastes 3-5).

PMID- 11973571
TI  - Training toxicity.

PMID- 11973572
TI  - Akathisia: problematic but preventable.

PMID- 11973573
TI  - A reservoir of talent waiting to be tapped.

PMID- 11973574
TI  - Awakening social capital.

PMID- 11973575
TI  - White paper on the health status of Filipino Americans and recommendations for
      research.

PMID- 11973576
TI  - National Alaska Native American Indian Nurses Association: reducing health
      disparities within American Indian and Alaska native populations.

PMID- 11973577
TI  - A data-based agenda for doctoral nursing education reform.
AB  - BACKGROUND: Continuing concerns over the diverse degree names and the quality and
      quantity of doctoral nursing programs make it essential that nursing leadership
      take consensus-driven action on the basis of today's educational realities.
      PURPOSE: To explore the state of US doctoral nursing education to determine what
      leadership initiatives are needed in program definition, scope, and resources.
      METHOD: The researchers used a mailed survey (63.4% response rate) and Web site
      review (all remaining progress) to gather data on all US doctoral nursing
      education programs (n = 87). The survey included 12 items pertaining to each
      degree program and 11 institutional environmental questions. DISCUSSION: The
      doctor of philosophy was the most common degree title (n = 71). Degree title was
      not consistently associated with requirements (eg, dissertation and practica
      requirements) or stated degree purposes. Reports of program resources, as defined
      by faculty rank and research experience, indicated fiscal and educational threats
      to program integrity in many schools. CONCLUSIONS: Although individual schools
      should continue efforts to increase educational quality, consensus and action by
      all doctoral programs is needed. Five recommendations for immediate action are
      proposed.

PMID- 11973578
TI  - Testing a theory of political development by comparing the political action of
      nurses and nonnurses.
AB  - BACKGROUND: Some nursing theories are available to guide the conceptualization,
      planning, and conduct of political action. Little initial or ongoing testing of
      these theories has taken place. PURPOSE: The purpose of this descriptive
      comparative investigation was to test the theory of Cohen et al (Cohen SS, Mason
      DJ, Kovner C, Leavitt JK, Pulcini J, Sochalski J. Stages of nursing's political
      development: where we've been and where we ought to go. Nurs Outlook 1996;44:259
      66) of political development stages through describing and comparing a specific
      example of political action by nurses and nonnurses. METHOD: Semistructured
      interviews of persons who spoke to a standing legislative committee about a
      proposed bill took place after the health care issues raised by this private bill
      were later addressed in a government act. Qualitative inquiry was used to gain an
      understanding of the subjects' perspectives. DISCUSSION: The political action
      undertaken by both nurses and nonnurses substantiated the first 2 of 4 theorized
      political stages. However, most nonnurses engaged in political action for self
      interest purposes, whereas nurses were oriented to the public good. This finding
      provides partial support for the third stage of Cohen et al, political
      sophistication. CONCLUSIONS: Nurses have consistently viewed themselves as
      patient advocates. It is not surprising then to see "other oriented" political
      activism by nurses at the community and societal level, because this is in
      keeping with the caring nature of nursing practice.

PMID- 11973580
TI  - Nursing has not changed.

PMID- 11973581
TI  - Vascular anomalies: From bedside to bench and back again.

PMID- 11973583
TI  - [Protective effect of low concentration endothelin-1 on the reactive oxygen
      induced inhibition of pulmonary surfactant lipid synthesis].
AB  - The effects of endothelin-1 (ET-1) at low concentration (1-100 pmol/L) on the
      reactive oxygen-induced inhibition of both pulmonary surfactant (PS) lipid
      synthesis and the activity of CTP: phosphorylcholine cytidylyltransferase (CCT),
      a rate-limiting enzyme in biosynthesis of phosphoatidylcholine (PC), were studied
      in cultured lung explants without serum. The xanthine-xanthine oxidase superoxide
      anion generating system decreased (3)H-choline incorporation into PC in a dose
      dependent manner in cultured lung explants. ET-1 reduced both the reactive oxygen
      induced decrease in (3)H-choline incorporation and the increase in
      malondialdehyde (MDA) content of lung tissues, but did not change the levels of
      antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and the total
      antioxidant capability in the lung explants. ET-1 enhanced microsomal CCT
      activity of the lung tissues, while it decreased cytosolic CCT activity of lung
      tissues. ET-1 also prevented the inhibitive effect of reactive oxygen on
      microsomal CCT activity in the lung explants. These results suggest that ET-1 at
      low concentration can protect the microsomal CCT activity and reduce the
      inhibition of PS lipid synthesis induced by oxidant lung injury. The protective
      mechanism of ET-1 is not relative to the pulmonary endogenous antioxidant defense
      system.

PMID- 11973584
TI  - [Effect of trigeminus nerve on facialis-denervated facial muscle atrophy].
AB  - In the present study we made out an animal model on rabbit whose trigeminus and
      facialis nerves were simultaneously or only the latter one was severed. The
      pathological changes in facial muscle atrophy under different nerve injuries were
      investigated. The degeneration of contractile proteins of upper lip muscle --
      myosin and actin was observed. In addition, we also examined the ultrastructural
      changes in the muscle atrophy in the two above-mentioned nerve injury cases. We
      observed that the intact trigeminus nerve could delay and lighten the atrophy of
      facialis-denervated facial muscle and attenuate the degeneration of myosin and
      actin, as well as decrease the increment of collagen and maintain the
      ultrastructure of the thick and thin muscle filaments. These results may provide
      the possibility of improvement of clinical treatment for facial muscle palsy.

PMID- 11973585
TI  - [Inhibitory effect of cholecystokinin-octapeptide on production of cytokines in
      the lung of endotoxic shock rats].
AB  - To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic
      hypotension and cytokine production in serum and lung of endotoxic shock (ES)
      rats induced by lipopolysaccharide (LPS) and investigate its signal transduction
      mechanism of p38 mitogen-activated protein kinase (MAPK), the changes in mean
      arterial pressure (MAP) were observed by using a polygraph in four groups of SD
      rats: group of LPS (8 mg/kg i.v.) induced ES, group of CCK-8 (40 microg/kg i.v.)
      pretreatment 10 min before LPS (8 mg/kg) administration, group of CCK-8 (40
      microg/kg i.v.) only, and normal saline (control) group; the contents of
      proinflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) in the lung and serum
      were assayed using ELISA kits; and p38 MAPK was detected by Western blot. The
      results showed that CCK-8 alleviated LPS-induced decrease in MAP of rats;
      compared with the control, LPS elevated the levels of TNF-alpha, IL-1 beta and IL
      6 in serum and lung significantly, while CCK-8 significantly inhibited the LPS
      induced increases in TNF-alpha, IL-1 beta and IL-6 in serum and lung. The
      activation of p38 MAPK in the lung of ES rats was enhanced by CCK-8 pretreatment.
      These results suggest that CCK-8 can alleviate the LPS-induced decrease in MAP of
      ES rats and exert an inhibitory effect on the overproduction of proinflammatory
      cytokines, and that p38 MAPK may be involved in its signal transduction
      mechanisms.

PMID- 11973586
TI  - [Effects of vasoactive intestinal peptide on chemotaxis of bronchial epithelial
      cells].
AB  - To investigate the influence of vasoactive intestinal peptide (VIP) on chemotaxis
      of bronchial epithelial cells (BECs). Rabbit chemotactic migration of primary BEC
      was assessed in a blind-well Boyden chamber. Radioimmunoassay and radio-ligand
      affinity analysis were used for determining VIP secretion and vasoactive
      intestinal peptide receptor (VIPR) expression. The results showed: (1) the method
      for determining chemotaxis of BECs by using insulin as chemotactic factor was
      stable and reproducible (r=0.9703, P<0.01). (2) VIP (0.001-1 micromol/L) elicited
      chemotaxis of BECs which was substantial and concentration-dependent. The effects
      of VIP were inhibited by W-7 and H-7 (P<0.01). (3) Heat stress enhanced the
      secretion of VIP (P<0.01) and upregulated the expression of VIPR on BECs
      (P<0.05). These results indicate that VIP in the lungs may play an important role
      in the repair of damaged epithelium, accelerating restoration of the airway to
      its normal state. Calmodulin and protein kinase C may be involved in the signal
      transduction of VIP effects.

PMID- 11973587
TI  - [Influence of regulatory peptides on the secretion of interleukins from bronchial
      epithelial cells of the rabbit].
AB  - To explore the role of regulatory peptides in the secretion of bronchial
      epithelial cells (BECs), we observed the effects of four peptides, i.e.vasoactive
      intestinal peptide (VIP), epidermal growth factor (EGF), endothelin-1 (ET-1), and
      calcitonin gene-related peptide (CGRP), on the secretion of ILs from unstimulated
      or O3-stressed BECs. The results of the experiments showed that VIP exerted an
      inhibitory effect on the secretion of IL-1 and IL-8 from unstimulated and O3
      stressed BECs, VIP also decreased the secretion of IL-5 from O3-stressed BECs;
      EGF promoted secretion of IL-1 and IL-8 from unstimulated BECs, but decreased the
      secretion of ILs from O3-stressed BECs; ET-1 and CGRP enhanced the secretion of
      IL-1, IL-5, and IL-8 from unstimlated BECs, CGRP also increased the secretion of
      ILs from O3-stressed BECs. The results obtained demonstrate that intrapulmonary
      regulatory peptides modulate the secretion of ILs from BECs, and may play an
      important part in transduction of inflammatory signals.

PMID- 11973588
TI  - [The activation of vagus afferent in response to lipopolysaccharide   the role of
      interleukin-1].
AB  - To study the possibility of activation of vagus afferent in response to
      lipopolysaccharide (LPS) through interleukin-1 (IL-1), Wistar rats were randomly
      divided into LPS group and saline (NS) group. The expression of c-Fos, CD14 and
      Mac-1 were detected by immunohistochemistry staining. IL-1 bioactivity was
      determined by L929 cell proliferation. The expression of IL-1R I mRNA was
      detected by in situ hybridization. Our results showed that there were some c-Fos
      protein expression positive neurons in the nodose ganglion in LPS group, but no c
      Fos protein expression positive neurons in the nodose ganglion in control group.
      The number of macrophages (M phi) in the connective tissue surrounding the
      abdominal vagus increased significantly in response to LPS i.p. Forty-five
      minutes after the application of LPS, the IL-1 bioactivity in the supernatant of
      M phi was increased. Positive IL-1R mRNA neurons were also observed in the nodose
      ganglion in the LPS group. The results indicate that vagus afferent is activated
      in response to LPS and that IL-1 production might be involved in the activation
      of vagus afferent.

PMID- 11973590
TI  - [Differential role of estrogen in dopamine metabolism in the amygdala and
      striatum of female rats].
AB  - To study the effects of estrogen on the contents of dopamine (DA) and its
      metabolites in the amygdala (Amy) and striatum (Str) of rats, high performance
      liquid chromatography (HPLC) was used to measure the contents of DA and its
      metabolites in untreated ovariectomized (OVX) rats and OVX rats treated with
      estrogen. The contents of DA and its metabolites in Amy but not Str were
      significantly higher when the OVX rats were treated with a high dose of estradiol
      benzoate (EB). The turnover rate of DA in Amy of the OVX rats was lower than that
      of normal and EB-treated OVX rats. The turnover rate of DA in Amy was about twice
      as high as in the Str, while the content of DA in Amy was only one-sixth of that
      in the Str. The results obtained imply that serum concentration of estrogen is
      one of the important factors which affect the DA metabolism and content in the
      Amy of female rats, while the Str is not influenced by estrogen.

PMID- 11973589
TI  - [Effects of rhIL-6 on Bcl-2 and Bax expression and apoptosis after anoxia
      reoxygenation in cultured rat hippocampal neurons].
AB  - The purpose of the present study was to determine the effects of recombinant
      human interleukin-6 (rhIL-6) on the Bcl-2 and Bax expression and apoptosis after
      anoxia-reoxygenation in cultured rat hippocampal neurons. The control and rhIL-6
      treated hippocampal neurons cultured for 12 d were exposed to anoxia environment
      (90% N2+10% CO2) for 2 and 4 h and then were reoxygenated for 24 and 72 h. The
      expression of Bcl-2 and Bax was revealed immunocytochemically using the antiserum
      against Bcl-2 and Bax. The apoptosis was examined by the terminal
      deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate
      nickel end labeling (TUNEL) method and flow cytometric analysis. The results
      showed that in cultured hippocampal neurons the Bcl-2 expression decreased while
      Bax expression and the percentage of apoptotic neurons increased after anoxia
      reoxygenation compared with those before anoxia. In comparison with the control,
      after anoxia-reoxygenation the Bcl-2 expression in hippocampal neurons was higher
      than that in rhIL-6 group; however the Bax expression and the percentage of the
      apoptosis were decreased in rhIL-6 group. It is suggested that rhIL-6 may play a
      role in protecting neurons from the damage induced by anoxia-reoxygenation.

PMID- 11973591
TI  - [Effects of electrical stimulation of the dorsal cutaneous branches of spinal
      nerves on the discharge activity of remote mechanoreceptive units in rats].
AB  - The method of isolating filaments of the dorsal cutaneous branches was used to
      observe the effects of antidromic electrical stimulation of the spinal nerves on
      the discharge of remote A delta and C mechanoreceptive units in rats. Seventy
      nine mechanoreceptive units were recorded from the T12 nerve filaments after
      stimulation of the dorsal cutaneous branches of T9 spinal nerve. It was found
      that the discharge frequency of 59.3% (16/27) A delta-units and 71.2% (37/52) C
      units significantly increased during 90-120 s after the stimulation. Sixty-four
      mechanoreceptive units were recorded from the T12 nerve filaments after
      stimulation of the dorsal cutaneous branches of T8 spinal nerves. The discharge
      frequency of 47.8% (11/23) A delta-units and 36.6% (15/41) C-units significantly
      increased during 120-150 s after the stimulation. In addition, the threshold of
      the majority of these mechanoreceptors (78.3%, 18/23) decreased after the
      stimulation. The results suggest that antidromic electrical stimulation of the
      dorsal cutaneous branches of spinal nerves leads to sensitization of A delta and
      C mechanoreceptive units of the remote peripheral nerve endings, which results in
      an increase in afferent discharge of these units.

PMID- 11973592
TI  - [The role of vagal innervation in the variability of heart beat].
AB  - To determine the role of vagi in heart rate variability, conscious rabbits were
      employed and electrocardiogram was recorded under conditions of bilateral vagi
      intact, unilateral vagotomy, and bilateral vagotomy. The variability of RR
      intervals (RRI) was analyzed using power spectrum and approximate entropy (ApEn).
      The results showed that the values of high frequency power (HF) component, low
      frequency power (LF) component and ApEn in animals with bilateral vagi intact
      were the highest, but the LF/HF ratio was the lowest; unilateral vagotomy
      decreased ApEn, right vagotomy increased LF/HF ratio but left vagotomy did not;
      the LF/HF ratio increased while ApEn decreased significantly in animals with
      bilateral vagotomy. It is suggested that the variability of RRI is mainly
      regulated by the vagi and the role of right vagi is more important than that of
      the left. When measuring heart rate variability, the results obtained with
      conventional method are consistent with those with nonlinear method.

PMID- 11973593
TI  - [Protective effects of paraventricular nucleus stimulation and vasopressin on
      gastric ischemia-reperfusion injury in rats].
AB  - The effects of paraventricular nucleus (PVN) stimulation and vasopressin on
      gastric ischemia-reperfusion injury (GI-RI) were investigated in male SD rats of
      which the celiac artery was clamped for 30 min and reperfused for 1 h by removal
      of the clamp. The results were as follows. Both electrical and chemical
      stimulation of the PVN obviously attenuated the GI-RI. Bilateral electrolytic
      lesion of the nucleus tractus solitarius (NTS) or microinjection of AVP-V(1)
      receptor antagonist into the NTS could eliminate the protective effect of
      electrical stimulation of the PVN on GI-RI. Hypophysectomy did not influence the
      effect of electrical stimulation of the PVN. Both vagotomy and sympathectomy
      could increase the effect of stimulating PVN on GI-RI. Microinjection of arginine
      vasopressin (AVP) into the PVN also attenuated the effect on GI-RI. These results
      suggest that the PVN and AVP participate in the regulation of GI-RI and play an
      important role in protection against GI-RI. This protective effect of PVN on GI
      RI might be mediated by activation of AVP-ergic neurons in the PVN, which release
      AVP from the descending projection fibers and activate the AVP-V(1) receptors on
      the NTS neurons. The vagus and sympathetic nerves are involved in the efferent
      pathway exerting their effects on GI-RI. Hypophysis does not seem to be involved
      in the protective effect of PVN stimulation.

PMID- 11973594
TI  - ATP-sensitive potassium channels and endogenous adenosine are involved in spinal
      antinociception produced by locus coeruleus stimulation.
AB  - It has been known that locus coeruleus (LC) stimulation suppresses nociceptive
      discharges of the thalamic parafascicular (PF) neurons through the spinally
      descending adrenergic terminals which inhibit the transmission of nociceptive
      signals in the spinal dorsal horn. This experimental model was used in the
      present study to analyze the detailed processes that happened in the dorsal horn
      following norepinephrine release by preemptive intrathecal (i.t.) administration
      of related drugs in lightly urethane-anesthetized rats. The results showed that:
      (1) LC stimulation significantly inhibited the noxiously-evoked discharges of PF
      neurons; (2) the LC stimulation-produced antinociception in PF neurons could be
      blocked either by i.t. glibenclamide, an ATP-sensitive potassium (K(+)(ATP))
      channel blocker, or by i.t. aminophylline, an adenosine receptor antagonist; (3)
      nociceptive discharges of PF neurons were also suppressed both by i.t. 5  -N
      ethylcarboxamido-adenosine (NECA, an adenosine receptor agonist) and by i.t.
      nicorandil (a K(+)(ATP) channel opener); and (4) i.t. aminophylline blocked the
      suppression of PF nociceptive discharges induced by i.t. nicorandil, while i.t.
      glibenclamide showed no effect on the suppression of nociceptive discharges
      induced by i.t. NECA. These results suggest that: (1) K(+)(ATP) channels and
      endogenous adenosine may be involved in the mediation of spinal antinociception
      induced by descending adrenergic fibers originating from the LC; and (2) the
      opening of K(+)(ATP) channels precedes the release of adenosine in the cascade of
      mediation.

PMID- 11973595
TI  - [Relationship between proliferation of vascular smooth muscle cells and PDGF-AA
      and PDGFR-alpha expression in SHRs].
AB  - To explore the role of platelet derived growth factor-AA (PDGF-AA) and PDGFR
      alpha expression in the proliferation and hypertrophy of vascular smooth muscle
      cells (VSMCs) in spontaneously hypertension rats (SHR), protein expression of
      PDGF-AA, PDGFR-alpha and PDGFR-beta in SHR/Wistar-Kyoto (WKY)-VSMC was observed
      by Western blot. Proliferation and hypertrophy of SHR-VSMCs induced by PDGF-AA
      were observed by measurement of PCNA and [(3)H] incorporation. PDGF-AA and PDGFR
      alpha expression was markedly increased in SHR-VSMCs compared with that in WKY
      VSMCs, but PDGFR-beta was not different in SHR and WKY-VSMCs. PDGF-AA induced
      PCNA expression and [(3)H] incorporation was increased in a dose-dependent manner
      in SHR, but not in WKY. It is suggested that an enhancement of PDGF-AA and PDGFR
      alpha in SHRs may be one of the important factors for vascular modeling.

PMID- 11973596
TI  - [Effect of angiotensin II on potassium channels of ischemic ventricular myocytes
      of the guinea pig].
AB  - The experiments were carried out on guinea pig isolated ventricular myocytes by
      using whole-cell patch clamp. The effects of angiotensin II (Ang II) on potassium
      ion channels of acute ischemic myocytes were observed. Whole-cell patch clamp
      recordings showed that physiological potassium current, including delayed
      rectifier potassium current and inward rectifier potassium current were inhibited
      under the condition of simulated ischemia, and then further inhibited by
      treatment with Ang II. ATP-sensitive potassium currents were increased under
      simulated ischemia and were further enhanced by Ang II treatment.

PMID- 11973597
TI  - [Effects of calcitonin gene-related peptide on repolarization process in isolated
      guinea-pig atrial myocardium at the physiological temperature].
AB  - The purpose of this study was to investigate the effects of calcitonin gene
      related peptide (CGRP) on the repolarization process in isolated guinea-pig
      atrial cells and to determine the contribution of K(+) channels to the CGRP
      induced changes in action potential using conventional microelectrode method at
      the physiological temperature. We found that: (1) CGRP (16 nmol/L) antagonized
      the influences of potassium channel blockers, 4-AP and BaCl2, on action
      potential; (2) CGRP (16 nmol/L) increased the amplitude and maximum depolarizing
      velocity of slow action potential and shortened the conducting time in guinea pig
      atrial myocardium at extracellular K(+) concentration of 18.5 mmol/L; (3) CGRP
      (16 nmol/L) alleviated triggered activity induced by superfusion with solution
      containing CsCl and no potassium ion; and (4) the effects of CGRP on the
      configuration of action potential were temperature-dependent. At the temperature
      of 36.5+/-0.5 degrees C, CGRP (5, 16, and 50 nmol/L) increased the amplitude of
      the action potential and shortened APD(20), APD(50) and APD(90). The CGRP effects
      on APD(20) and APD(50) were dose-dependent and reversible. On the contrary, CGRP
      prolonged APD(20), APD(50) and APD(90) at the temperature of 25.5+/-2.1 degrees
      C. The present study suggests that CGRP possesses multiple effects on various
      ionic channels. Among them the effects on potassium currents are major
      determinants in the changes in action potential induced by CGRP under
      physiological temperature. It is necessary to further study the influences of
      CGRP on different types of potassium channels.

PMID- 11973598
TI  - Role of platelet-derived growth factor receptor-mediated signal transduction in
      myocardial hypertrophy of spontaneously hypertensive rats.
AB  - The role of platelet-derived growth factor (PDGF) receptor-mediated signal
      transduction in myocardial hypertrophy of spontaneously hypertensive rats (SHR)
      was investigated. The protein expressions of PDGF beta receptor and extracellular
      signal-regulated kinase 1/2 (ERK 1/2) and the level of phosphorylated ERK 1/2
      (pERK 1/2) in cardiac tissues from 4- and 12-week-old SHR and their age-matched
      normotensive control Wistar-Kyoto rats (WKY) were examined by Western blot
      analysis. The results showed that arterial systolic and diastolic blood pressure,
      +/-dp/dt(max) and the ratio of left ventricular weight to body weight were
      unchanged in 4-week-old SHR, while they were increased significantly in 12-week
      old SHR as compared with those of age-matched WKY. There were no differences in
      PDGF beta receptor, pERK 1/2, and ERK 1/2 between 4-week-old WKY and SHR. The
      expression of PDGF beta receptor of 12-week-old SHR was significantly increased
      by 32.77% (P<0.05) as compared with that of age-matched WKY. Although the
      expression of ERK 1/2, the downstream signal molecule of PDGF receptor-mediated
      signal transduction pathway, was unchanged, the level of pERK 1/2, the active
      form of ERK 1/2, was increased by 19.6% (P=0.01) in 12-week-old SHR. To further
      elucidate the effect of PDGF beta receptor on cardiomyocyte growth and the
      relation between PDGF beta receptor and ERK 1/2 activity,   (3)H  leucine
      incorporation assay and immunoblotting analysis of pERK 1/2 were performed after
      cultured neonatal rat cardiomyocytes were stimulated with PDGF-BB. It was shown
      that   (3)H  leucine incorporation and pERK 1/2 level were significantly
      increased after PDGF-BB stimulation. These findings suggest that PDGF beta
      receptor may play an important role in the myocardial hypertrophy of
      spontaneously hypertensive rats.

PMID- 11973599
TI  - [Effects of insulin on the distribution of actins in vascular smooth muscle cells
      in the process of proliferation via mitogen-activated protein kinase in vitro].
AB  - Proliferation of vascular smooth muscle cells (VSMCs) is often accompanied by
      changes in intracellular actin distribution. The changes are controlled by the
      signal transduction pathways of protein kinase C/mitogenic activated protein
      kinase (PKC-MAPK), but the mechanism is unclear. In order to study the effect of
      insulin on the intracellular signal transduction (PKC-MAPK) probably involved in
      the modulation of proliferation and redistribution of actins in the VSMCs, the
      DNA synthesis, MAPK activities and its gene expression, and the redistribution of
      intracellular actins were investigated in the isolated VSMCs of SHR pretreated
      with PKC inhibitor and/or insulin, respectively. We found that insulin treatment
      resulted in proliferation of the VSMCs and an increase in [(3)H] TdR
      incorporation. Meanwhile, the activities and expression of MAPK increased
      significantly compared to the control group. These effects of insulin were
      blocked by PKC inhibitor. In addition, insulin caused a redistribution of the
      intracellular actins in VSMCs, which was also inhibited by PKC inhibitor. It is,
      therefore, suggested that these effects of insulin on VSMCs proliferation and
      distribution of the intracellular actins may be mediated by the MAPK signal
      transduction pathway.

PMID- 11973600
TI  - [A preliminary study on the immune suppressive protein of stress in human
      tonsil].
AB  - Our previous work demonstrated that under the conditions of restraint stress and
      under the control of central nervous system (CNS), an immune suppressive protein
      of stress (ISPS) was generated in peripheral lymph tissue and released into the
      blood stream, acting as an immune suppressor. In the present work, a protein
      similar to ISPS was found in human tonsil (a peripheral lymph tissue). Human
      tonsil was homogenized and the extract was prepared. It was found that lymphocyte
      proliferation was significantly suppressed by the extract. The suppression
      induced by the extract was partially reversed by the monoclonal antibody against
      ISPS (2C4). In ELISA test, the extract was able to bind to the monoclonal
      antibody. By immunohistochemistry, many ISPS positive cells were found in human
      tonsil. The ISPS positive cells were also found in human lymph nodes. Taken
      together, all the results demonstrate that a protein similar to ISPS may exist in
      human peripheral lymphoid tissue.

PMID- 11973601
TI  - [The expression of neuronal nitric oxide synthase in caudal medulla of two-kidney
      one clip Goldblatt hypertension rat].
AB  - Experiments were performed in male Sprague-Dawley rats (150-200 g). A silver clip
      (0.2 mm internal diameter) was placed on the left renal artery of rats. After
      operation the rats were divided into 4 groups sham group, 2K1C (two-kidney one
      clip) group, 2K1C+Arg (2K1C and L-Arg 150 mg/kg x d(-1) by drinking) group, and
      2K1C+NAME (2K1C and L-NAME 10 mg/kg x d(-1) i.p.) group. The animals were studied
      at two time points (4 and 7 weeks after operation) corresponding to phases I and
      II of Goldblatt hypertension. The animals were deeply anesthetized with
      pentobarbital and perfused by the cardiac route with saline (100 ml) and freshly
      prepared 4% paraformaldehyde in phosphate buffer (300 ml). The caudal medulla was
      removed, then placed in 25% sucrose in PB for 12 h in a 4 degrees C fridge. The
      40 microm coronal slices of brainstems were cut with cryostat, collected in PBS
      for nNOS study by immunohistochemistry. The results showed that (1) only a few
      neuronal nitric oxide synthase (nNOS) positive neurones were found in caudal
      medulla, including the depressor area of the ventral surface of medulla oblongata
      (VSMd) and the caudal pressor area (CPA) of the sham operated animals. The number
      of nNOS positive neurons in caudal medulla was significantly increased in 2K1C
      Goldblatt hypertension rats at 4 and 7 weeks. (2) The number of nNOS positive
      neurons in VSMd and CPA were 2K1C+Arg > 2K1C >2K1C +NAME > sham. (3) L-Arg
      enhanced the expression of nNOS whereas L-NAME inhibited the expression of nNOS
      in caudal medulla. (4) The character of nNOS expression was similar in Goldblatt
      hypertension rats at 4 weeks with that of the rats at 7 weeks.

PMID- 11973602
TI  - [Intracellular dialysis with a microcatheter inserted into the patch-clamp
      pipette].
AB  - In this paper we present an easily available method of intracellular dialysis via
      a microcatheter inserted into glass pipette during patch clamp experiment. An
      oblique hole through the glass pipette holder (above the lateral hole for cell
      seal suction) is drilled, through which a microcatheter (O.D.=0.1 mm) made from
      the universal pipetter tip by hand-drawing passes and sticks out of the holder
      mouth in parallel with the Ag-AgCl electrode. With a syringe connected to the
      microcatheter, substitution of intracellular solution and intracellular dialysis
      of drugs can be achieved easily. Compared with repatch technique and
      intracellular solution substitution techniques used abroad, this method operates
      more easily and can produce more reliable results.

PMID- 11973603
TI  - Idiopathic juvenile osteoporosis.

PMID- 11973604
TI  - Does cytoskeleton 'Akt' in apoptosis?

PMID- 11973605
TI  - Parkinsonism proteolysis and proteasomes.

PMID- 11973606
TI  - Size matters: of the small HSP27 and its large oligomers.

PMID- 11973607
TI  - Apoptosis and keratin intermediate filaments.
AB  - Intermediate filament (IF) proteins utilize central alpha-helical domains to
      generate polymeric fibers intermediate in size between actin microfilaments and
      microtubules. The regions flanking the central structural domains have diverged
      greatly to permit IF proteins to adopt specialized functions. Keratins represent
      the largest two groups of IF proteins. Most keratins serve structural functions
      in hair or epidermis. Intracellular epidermal keratins also provide strength to
      epithelial sheets. The intracellular type I keratins and other IF proteins are
      cleaved by caspases during apoptosis to ensure the disposal of the relatively
      insoluble cellular components. However, recent studies have also revealed an
      unexpected protective role for keratin 8 during TNF and Fas mediated apoptosis.
      Evidence for possible functions of keratins both upstream and downstream of
      apoptotic signaling are considered.

PMID- 11973608
TI  - Rho GTPase signalling pathways in the morphological changes associated with
      apoptosis.
AB  - The killing and removal of superfluous cells is an important step during
      embryonic development, tissue homeostasis, wound repair and the resolution of
      inflammation. A specific sequence of biochemical events leads to a form of cell
      death termed apoptosis, and ultimately to the disassembly of the dead cell for
      phagocytosis. Dynamic rearrangements of the actin cytoskeleton are central to the
      morphological changes observed both in apoptosis and phagocytosis. Recent
      research has highlighted the importance of Rho GTPase signalling pathways to
      these changes in cellular architecture. In this review, we will discuss how these
      signal transduction pathways affect the structure of the actin cytoskeleton and
      allow for the efficient clearance of apoptotic cells.

PMID- 11973609
TI  - Keeping killers on a tight leash: transcriptional and post-translational control
      of the pro-apoptotic activity of BH3-only proteins.
AB  - BH3-only proteins are structurally distant members of the Bcl-2 protein family
      that trigger apoptosis. Genetic experiments have shown that these proteins are
      essential initiators of programmed cell death in species as distantly related as
      mice and C. elegans. BH3-only proteins share with each other and with the
      remainder of the Bcl-2 family only a nine amino acid BH3 (Bcl-2 Homology) region.
      Mutational analyses have demonstrated that this domain is required for their
      ability to bind to Bcl-2-like pro-survival proteins and to initiate apoptosis. So
      far only one BH3-only protein, EGL-1, has been identified in C. elegans and it is
      required for all developmentally programmed death of somatic cells in this
      species. In contrast, mammals have at least 10 BH3-only proteins that differ in
      their expression pattern and mode of activation. Studies in gene targeted mice
      have indicated that different BH3-only proteins are required for the initiation
      of distinct apoptotic stimuli. The pro-apoptotic activities of BH3-only proteins
      are stringently controlled by a variety of mechanisms. C. elegans egl-1 as well
      as mammalian hrk/dp5, noxa, puma/bbc3 and bim/bod are regulated by a diverse
      range of transcription factors. Certain BH3-only proteins, including Bad,
      Bik/Nbk, Bid, Bim/Bod and Bmf, are restrained by post-translational modifications
      that cause their sequestration from pro-survival Bcl-2 family members. In this
      review we describe current knowledge of the functions and transcriptional as well
      as post-translational control mechanisms of BH3-only proteins.

PMID- 11973611
TI  - Accumulation of an inactive form of p53 protein in cells treated with TNF alpha.
AB  - In MCF-7 cells, TNF alpha induces a G1 arrest with an increased expression of
      p21/Waf1, an activation of NF-kappa B and an accumulation of p53. NF-kappa B and
      p53 are two transcriptional factors known to activate p21/Waf1 gene expression.
      Here we show that p53 inhibition has no effect on p21/Waf1 mRNA accumulation
      following TNF alpha treatment. In contrast, inactivation of NF-kappa B inhibits
      p21/Waf1 expression without affecting G1 arrest. The fact that p21/Waf1 gene
      expression is still stimulated when p53 is inactivated strongly suggests that TNF
      alpha induces accumulation of an inactive form of p53 protein. This assumption
      was further supported by the following observations: (i) the p53 DNA-binding
      activity to its consensus sequence was not stimulated following TNF alpha
      treatment, (ii) phosphorylation at Ser-15, -20 or -392 was not detected in
      response to TNF alpha, (iii) the transcription rate of Ddb2, another p53 target
      gene, was not stimulated by TNF alpha. Finally, the accumulation of p53 in the
      nuclei of TNF alpha-treated MCF-7 cells was concomitant with an increase in p53
      mRNA level, suggesting a regulation at the transcription level.

PMID- 11973610
TI  - Ligand activation of peroxisome proliferator-activated receptor gamma induces
      apoptosis of leukemia cells by down-regulating the c-myc gene expression via
      blockade of the Tcf-4 activity.
AB  - The peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of
      the nuclear receptor superfamily, is expressed at highest levels in adipose
      tissue and functions as a central regulator in the process of adipocyte
      differentiation. In the present study, we showed that human leukemic cell lines,
      not only myeloid but also lymphoid, express PPAR gamma and its activation by
      natural ligand (15-deoxy-Delta(12,14) - prostaglandin J(2)) and synthetic ligand
      (troglitazone) profoundly inhibited their proliferation by induction of apoptosis
      preferentially in the serum-free culture. We pursued its mechanism using the
      representative cell lines, and found that induction of apoptosis was accompanied
      by caspase-3 activation and specifically blocked by its inhibitor. While status
      of several apoptosis-related molecules remained unchanged, the c-Myc expression
      was markedly down-regulated within 24 h after troglitazone treatment. The c-myc
      mRNA levels were dramatically reduced at 1 h and became undetectable at 12 h
      after troglitazone treatment, which proved to be accompanied by complete blockade
      of the Tcf-4 activity in the electrophoretic mobility shift assay. We succeeded
      in establishing HL-60 cell lines growing well in the presence of troglitazone in
      the long-term serum-free culture. They showed neither induction of apoptosis nor
      down-regulation of the c-Myc expression via blockade of the Tcf-4 activity after
      troglitazone treatment. This is the first identification of the linkage between
      PPAR gamma-mediated apoptosis and down-regulation of the c-myc gene expression.

PMID- 11973612
TI  - Release of intact, monomeric cytochrome c from apoptotic and necrotic cells.
AB  - Cytochrome c (Cyt c) has been shown to translocate from mitochondria to the
      cytoplasm of cells early in apoptosis. In this study sandwich ELISAs for Cyt c
      were used to determine if Cyt c is ultimately released from apoptotic and
      necrotic cells. Gel-filtration and cation-exchange chromatographies, in
      conjunction with immunoreactivity in ELISA, and Western blotting were employed to
      examine the integrity of the released Cyt c. The results show that Cyt c is
      released from both apoptotic and necrotic cells in an intact, monomeric form. The
      release of Cyt c from apoptotic splenocytes began within 2 h following apoptotic
      insult, while Cyt c was immediately released following induction of necrosis by
      heat shock. These findings may be relevant to understanding how Cyt c becomes a
      target for antibody production in some patients with systemic autoimmune
      diseases.

PMID- 11973613
TI  - p53 and Fas ligand are required for psoralen and UVA-induced apoptosis in mouse
      epidermal cells.
AB  - A combination of 8-methoxypsoralen (8-MOP) and ultraviolet-A (UVA) radiation (320
      400 nm) (PUVA) is widely used in the treatment of psoriasis and other skin
      diseases. PUVA is highly effective in eliminating hyperproliferative cells in the
      epidermis, but its mechanism of action has not been fully elucidated. In this
      study, we used immortalized JB6 mouse epidermal cells, p53(-/-), and Fas ligand
      deficient (gld) mice to investigate the molecular mechanism by which PUVA induces
      cell death. The results indicate that PUVA treatment induces apoptosis in JB6
      cells. In addition, PUVA treatment of JB6 cells results in p53 stabilization,
      phosphorylation, and nuclear localization as well as induction of p21(Waf/Cip1)
      and caspase-3 activity. In vivo studies reveal that PUVA treatment induces
      significantly less apoptosis in the epidermis of p53(-/-) mice compared to
      p53(+/+) mice. Furthermore, FasL-deficient (gld) mice are completely resistant to
      PUVA-induced apoptosis compared to wild-type mice. These results indicate that
      PUVA treatment induces apoptosis in mouse epidermal cells in vitro and in vivo
      and that p53 and Fas/Fas ligand interactions are required for this process, at
      least in vivo. This implies that similar mechanisms may be involved in the
      elimination of psoriatic keratinocytes from human skin following PUVA therapy.

PMID- 11973614
TI  - A supramicromolar elevation of intracellular free calcium ([Ca(2+)](i)) is
      consistently required to induce the execution phase of apoptosis.
AB  - Many agents, such as the endoplasmic reticulum Ca(2+) ATPase inhibitor,
      thapsigargin, or the ionophore, ionomycin, induce apoptosis by transiently
      elevating [Ca(2+)](i). The role of [Ca(2+)](i) in apoptosis induced by agents
      that do not immediately increase [Ca(2+)](i), such as 5-FdUr, TGF beta-1,
      doxorubicin, or radiation, is far more controversial. In the present paper,
      [Ca(2+)](i) was measured continuously for 120 h. in prostate and bladder cancer
      cell lines exposed to these four agents: 5-FdUR, TGF beta-1, doxorubicin, or
      radiation. Each of them consistently induced a delayed [Ca(2+)](i) rise
      associated with the morphological changes that characterize the execution phase
      of apoptosis (i.e. rounding, blebbing). This [Ca(2+)](i) rise occurred in two
      consecutive steps (< or = 10 microM and >10 microM) and resulted from a Ca(2+)
      influx from the extracellular medium. This delayed supramicromolar [Ca(2+)](i)
      rise was also observed previously in breast, prostate and bladder cancer cell
      lines exposed to thapsigargin. This influx regulated transcriptional
      reprogramming of Gadd153 and is required to activate cytochrome c release,
      caspase-3 activation, loss of clonal survival and DNA fragmentation. When cells
      were maintained in low extracellular Ca(2+) media, these phenomena were
      temporarily delayed but occurred on return to normal Ca(2+) medium. Similarly,
      apoptosis could be delayed by overexpressing the Ca(2+)-binding proteins,
      Calbindin-D(28K) and parvalbumin. As this delayed >or = 10 microM [Ca(2+)](i)
      elevation was observed in a number of cell lines exposed to a variety of
      different agents, we conclude that such elevation constitutes a key and general
      event of apoptosis in these malignant cells.

PMID- 11973615
TI  - Fas, ceramide and serum withdrawal induce apoptosis via a common pathway in a
      type II Jurkat cell line.
AB  - Ceramide is a key mediator of apoptosis, yet its role in Fas-mediated apoptosis
      is controversial. Some reports have indicated that ceramide is either a primary
      signaling molecule in Fas-induced cell death, or that it functions upstream of
      Fas by increasing FasL expression. Other studies have suggested that ceramide is
      not relevant to Fas-induced cell death. We have approached this problem by
      studying ceramide-induced apoptosis in unique Jurkat cell clones selected for
      resistance to membrane-bound FasL-induced death. Resistance of the mutant Jurkat
      cells was specific for FasL killing, since the mutant clones were sensitive to
      other apoptotic stimuli such as cycloheximide and staurosporine. We tested the
      effects of serum withdrawal, one of the strongest inducers of ceramide, and of
      exogenous ceramide on apoptosis of both wild-type and FasL-resistant clones. Wild
      type Jurkat cells were remarkably sensitive to serum withdrawal and to exogenous
      ceramide. In contrast all FasL-resistant mutant clones were resistant to these
      apoptosis-inducing conditions. In contrast to previous work, we did not detect an
      increase in FasL in either wild-type or mutant clones. Moreover activation of
      stress-activated protein kinases (JNK/SAPKs) after serum withdrawal and exogenous
      ceramide treatment was detected only in the wild-type and not in the resistant
      clones. Because of the parallel resistance of the mutant clones to Fas and to
      ceramide-induced apoptosis, our data support the notion that ceramide is a second
      messenger for the Fas/FasL pathway and that serum withdrawal, through production
      of ceramide, shares a common step with the Fas-mediated apoptotic pathway.
      Finally, our data suggest that activation of JNK/SAPKs is a common mediator of
      the three pathways tested.

PMID- 11973616
TI  - AP-1, but not NF-kappa B, is required for efficient steroid-triggered cell death
      in Drosophila.
AB  - Extensive studies in vertebrate cells have assigned a central role to Rel/NF
      kappa B and AP-1 family members in the control of apoptosis. We ask here whether
      parallel pathways might function in Drosophila by determining if Rel/NF-kappa B
      or AP-1 family members contribute to the steroid-triggered death of larval
      salivary glands during Drosophila metamorphosis. We show that two of the three
      Drosophila Rel/NF-kappa B genes are expressed in doomed salivary glands and that
      one family member, Dif, is induced in a stage-specific manner immediately before
      the onset of programmed cell death. Similarly, Djun is expressed for many hours
      before salivary gland cell death while Dfos is induced in a stage-specific
      manner, immediately before this tissue is destroyed. We show that null mutations
      in the three Drosophila Rel/NF-kappa B family members, either alone or in
      combination, have no apparent effect on this death response. In contrast, Dfos is
      required for the proper timing of larval salivary gland cell death as well as the
      proper induction of key death genes. This study demonstrates a role for AP-1 in
      the stage-specific steroid-triggered programmed cell death of larval tissues
      during Drosophila metamorphosis.

PMID- 11973617
TI  - The European death flying circus.

PMID- 11973618
TI  - Emery-Dreifuss muscular dystrophy.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is characterised by early contractures,
      slowly progressive muscle wasting and weakness with a distinctive humero-peroneal
      distribution and cardiac conduction defects leading to dilated cardiomyopathy.
      The genes known to be responsible for EDMD encode proteins associated with the
      nuclear envelope: the emerin and the lamins A and C.

PMID- 11973619
TI  - Postaxial polydactyly type A/B (PAP-A/B) is linked to chromosome 19p13.1-13.2 in
      a Chinese kindred.
AB  - Postaxial polydactyly is characterised by fifth digit duplications in hands
      and/or feet. Two phenotypic varieties have been described. In type A, the extra
      digit is well formed and articulates with the fifth or an extra metacarpal. A
      rudimentary extra fifth digit characterises type B. Mutations in the GLI3 gene
      are associated with postaxial polydactyly in some families and a second locus has
      been identified on chromosome 13 but the majority of cases remain unexplained. We
      report here a third locus for postaxial polydactyly on chromosome 19p13.1-13.2 in
      a large Chinese kindred with a combination of type A and B. Two-point linkage
      analysis showed the highest LOD score (Z(max) = 5.85 at theta; = 0 cM) at marker
      D19S221. Recombination events with markers D19S1165 and D19S929 define the
      critical region for this postaxial polydactyly locus to a region of 4.3 cM on the
      genetic map.

PMID- 11973620
TI  - Predictive DNA-testing for Huntington's disease and reproductive decision making:
      a European collaborative study.
AB  - This European collaborative study addresses the question whether a predictive
      test result for Huntington's disease (HD) has an effect on subsequent
      reproduction by comparing carriers and non-carriers of the Huntington mutation. A
      unique characteristic of this study is that this evaluation is done in persons at
      reproductive age who had a predictive test after the identification of the
      Huntington gene and who were counselled in one of the participating centres. Data
      were collected for 180 carriers and 271 non-carriers who received a predictive
      test result in the period 1993-1998 in Aberdeen, Athens, Cardiff, Leiden, Leuven,
      Paris or Rome. The mean age of the total study group was 31.5 years and for about
      half of the group the follow-up interval was 3 years or more, with a maximum of 7
      years. The collaborative study clearly revealed an overall impact of the
      predictive test result on subsequent reproduction: 14% of the carriers had one or
      more subsequent pregnancies vs 28% of the non-carriers. In the total carrier
      group a prenatal test was carried out in about two thirds of the pregnancies and
      one child was born after preimplantation genetic diagnosis; artificial
      insemination by donor, egg cell donation or adoption were not reported. A more
      refined analysis was performed in the subgroup with a follow-up interval of at
      least 3 years and who reported 'family planning' as a motive to apply for
      predictive testing in the pretest period. The complexity of this motive is
      discussed. In this subgroup with a desire for children in the pretest period the
      effect of the predictive test result was more pronounced: 69% of the non-carriers
      had subsequent pregnancies while only 39% of the carriers who mentioned 'family
      planning' as one of the major reasons to apply for predictive testing had a
      subsequent pregnancy. Of the carriers with one or more subsequent pregnancies the
      percentage using prenatal diagnosis was slightly higher than the percentage not
      using it, although there were clear differences from one centre to another. The
      latter group's decisions may seem more intriguing but may be partially understood
      based on stage theories of health behaviour. Last, but not least, whatever option
      is chosen by a couple at increased risk of transmitting the Huntington mutation,
      it is of the utmost importance that professionals fully respect this decision and
      support the couple.

PMID- 11973621
TI  - A detailed genetic map of the chromosome 7 bronchial hyper-responsiveness locus.
AB  - Non-specific bronchial hyper-responsiveness to various inhaled stimuli is a
      characteristic of asthma. We have previously shown linkage of bronchial
      responsiveness to methacholine (measured as dose-response slope (DRS)) and the
      peripheral blood eosinophil count (EOS) to chromosome 7. We have now further
      investigated these linkages by genotyping 49 microsatellite markers across the
      DRS locus on chromosome 7. The markers were spaced on average 2.6 cM apart and
      spanned a sex averaged cumulative genetic distance of 129 cM. Multipoint linkage
      to DRS was bimodal and dipped at the centromere. The two peaks of linkage were
      close to markers D7S484 (P=0.0003) and D7S669 (P=0.006) respectively. Separate
      testing for linkage to paternally and maternally derived alleles showed that the
      linkage near D7S484 was paternally derived (P<0.00001): maternally derived
      alleles did not exhibit significant linkage. The results indicate that two
      disparate loci may be influencing asthma from chromosome 7.

PMID- 11973622
TI  - Hirschsprung associated GDNF mutations do not prevent RET activation.
AB  - Hirschsprung disease (HSCR) is a complex disorder characterised by aganglia of
      distal gastrointestinal tracts. The highest proportion of both familial and
      sporadic cases is due to mutations of the RET proto-oncogene. Five germline
      mutations in the glial cell-line-derived neurotrophic factor (GDNF) gene, one of
      the RET ligands, have been detected in HSCR patients. Pedigrees analysis and the
      observed association between these GDNF alterations and RET variants in the same
      patients raised the question of whether the GDNF gene plays any
      causative/predisposing role in HSCR pathogenesis. In the present work, we have
      studied the ability of GDNF proteins, each bearing one of the reported mutations,
      to activate RET by performing a functional test in cultured neuroblastoma cells.
      Consistently with the lack of genotype/phenotype correlation in human subjects,
      our results indicate absence of detectable alterations of mutant GDNF induced RET
      activation.

PMID- 11973623
TI  - A novel recessive hyperekplexia allele GLRA1 (S231R): genotyping by MALDI-TOF
      mass spectrometry and functional characterisation as a determinant of cellular
      glycine receptor trafficking.
AB  - Hyperekplexia or startle disease (stiff baby syndrome, STHE) is a hereditary
      neurological disorder characterised by an exaggerated startle response and
      infantile muscle hypertonia. Several autosomal dominant and recessive forms of
      the disorder have been associated with point mutations in GLRA1, the human gene
      encoding the alpha 1 subunit of the inhibitory glycine receptor. Here, we
      describe a recessive point mutation (C1073G) in exon 7 of GLRA1 leading to an
      amino acid exchange of serine 231 to arginine in transmembrane region TM1. The
      mutation was detectable by restriction digest analysis of genomic PCR amplimers
      by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry
      (MALDI-TOF-MS). Genotyping of family members was performed using an allele
      specific primer extension assay in combination with MALDI-TOF-MS and confirmed by
      conventional DNA sequencing. These studies demonstrate the broad applicability of
      MALDI-TOF-MS as a comparative screening tool applicable to the analysis of
      allelic gene variants. In comparison to the wild type alpha 1 subunit,
      biochemical, electrophysiological, and confocal microscopy data indicate a
      reduced integration of functional alpha 1(S231R) glycine receptors into the cell
      surface membrane upon recombinant expression. Apparently, the amino acid exchange
      S231R influences glycine receptor biogenesis and cellular trafficking by
      introducing a positive charge into transmembrane region TM1.

PMID- 11973624
TI  - The ABCA4 2588G>C Stargardt mutation: single origin and increasing frequency from
      South-West to North-East Europe.
AB  - Inherited retinal dystrophies represent the most important cause of vision
      impairment in adolescence, affecting approximately 1 out of 3000 individuals.
      Mutations of the photoreceptor-specific gene ABCA4 (ABCR) are a common cause of
      retinal dystrophy. A number of mutations have been repeatedly reported for this
      gene, notably the 2588G>C mutation which is frequent in both patients and
      controls. Here we ascertained the frequency of the 2588G>C mutation in a total of
      2343 unrelated random control individuals from 11 European countries and 241
      control individuals from the US, as well as in 614 patients with STGD both from
      Europe and the US. We found an overall carrier frequency of 1 out of 54 in
      Europe, compared with 1 out of 121 in the US, confirming that the 2588G>C ABCA4
      mutation is one of the most frequent autosomal recessive mutations in the
      European population. Carrier frequencies show an increasing gradient in Europe
      from South-West to North-East. The lowest carrier frequency, 0 out of 199 (0%),
      was found in Portugal; the highest, 11 out of 197 (5.5%), was found in Sweden.
      Haplotype analysis in 16 families segregating the 2588G>C mutation showed four
      intragenic polymorphisms invariably present in all 16 disease chromosomes and
      sharing of the same allele for several markers flanking the ABCA4 locus in most
      of the disease chromosomes. These results indicate a single origin of the 2588G>C
      mutation which, to our best estimate, occurred between 2400 and 3000 years ago.

PMID- 11973625
TI  - Spinocerebellar ataxia type 1 (SCA1): phenotype-genotype correlation studies in
      intermediate alleles.
AB  - CAG repeat expansions with loss of CAT interruptions in the coding region of the
      ataxin-1 gene are associated with spinocerebellar ataxia type 1 (SCA1). For
      molecular genetic diagnosis it is necessary to define the limits of normal and
      pathological size ranges. In most studies, normal alleles as measured by PCR
      range from 6-39 units with interruptions of 1-3 CAT trinucleotides that are
      thought to be involved in the stability of the trinucleotide stretch during DNA
      replication. Expanded alleles have been reported to carry 39-81 CAG
      trinucleotides without stabilising CAT interruptions. To evaluate the limits
      between normal and disease size ranges we analysed the repeat length and
      composition of the SCA1 gene in 15 individuals with alleles ranging from 36 and
      41 triplets for genotype-phenotype correlation studies. We found the 39
      trinucleotide-allele to be either interrupted by CAT repeats or formed by a pure
      CAG stretch. The clinical features of individuals carrying 39 uninterrupted CAG
      repeats did not differ from the SCA1 phenotype in general with dysphagia, pale
      discs, pyramidal signs and cerebellar tremor being more frequent as compared to
      other SCA genotypes. In contrast, the interrupted 39 trinucleotide-allele is not
      correlated with the SCA1 phenotype.

PMID- 11973626
TI  - DFNB31, a recessive form of sensorineural hearing loss, maps to chromosome 9q32
      34.
AB  - We report the identification of a novel locus responsible for an autosomal
      recessive form of hearing loss (DFNB) segregating in a Palestinian consanguineous
      family from Jordan. The affected individuals suffer from profound prelingual
      sensorineural hearing impairment. A genetic linkage with polymorphic markers
      surrounding D9S1776 was detected, thereby identifying a novel deafness locus,
      DFNB31. This locus could be assigned to a 9q32-34 region of 15 cM between markers
      D9S289 and D9S1881. The whirler (wi) mouse mutant, characterised by deafness and
      circling behaviour, maps to the corresponding region on the murine chromosome 4,
      thus suggesting that DFNB31 and whirler may result from orthologous gene defects.

PMID- 11973627
TI  - Inherited and de novo mutations in sporadic cases of DYT1-dystonia.
AB  - A study of Danish probands with primary torsion dystonia is presented. The
      probands were examined clinically and biochemically to exclude secondary
      dystonia. Mutation analyses for the GAG-deletion in the DYT1 gene were performed
      on 107 probands; and the mutation was detected in three. All three probands had
      the classical phenotype of DYT1-dystonia, but only one had a family history of
      dystonia. The other two probands had, obviously, sporadic DYT1-dystonia, one of
      which was caused by a de novo mutation, while the other one had a parent being an
      asymptomatic carrier. De novo mutations in the DYT1 gene are seldom reported
      although independent founder mutations are known to have occurred. The frequency
      of DYT1-dystonia was low in our study even though several probands had early
      onset generalised dystonia. None of the probands in our study with other types of
      dystonia had the GAG-deletion as reported in other studies. The difficulties in
      genetic counselling concerning the heterogeneity of dystonia exemplified by DYT1
      dystonia are outlined.

PMID- 11973628
TI  - Chronic recurrent multifocal osteomyelitis (CRMO): evidence for a susceptibility
      gene located on chromosome 18q21.3-18q22.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is characterised by recurrent
      inflammatory lesions in the metaphyses of long bones and usually affects children
      and adolescents. Similarity with an autosomal recessive mouse disorder (cmo,
      chronic multifocal osteomyelitis) prompted us to perform a family based
      association study with two markers on chromosome 18q in the region homologous to
      the cmo localisation of the mouse. We found a significant association of CRMO
      with a rare allele of marker D18S60, resulting in a haplotype relative risk (HRR)
      of 18. This suggests the existence of a gene in this region contributing in a
      significant manner to the aetiology of CRMO and concomitantly demonstrates
      evidence for a genetic basis of CRMO for the first time. This gene is different
      from RANK, which is mutated in familial expansile osteolysis (FEO), but not in
      CRMO. Mutation screening in RANK and the genes PIGN and KIAA1468 led to detection
      of two variants (one in RANK and one in PIGN), which are in linkage
      disequilibrium with the rare D18S60 allele, but not independently associated with
      CRMO.

PMID- 11973629
TI  - Transient blocking of both B7.1 (CD80) and B7.2 (CD86) in addition to CD40-CD40L
      interaction fully abrogates the immune response following systemic injection of
      adenovirus vector.
AB  - Blockade of the CD40-CD40L and CD80/CD86-CD28 costimulatory pathways represents a
      strategy to inhibit the immune response against Ad vectors designed for gene
      therapy applications. Since most previous studies have used a CTLA4-Ig fusion
      molecule binding to both CD80 and CD86, the respective roles of these B7
      molecules remained undefined. We have studied the effect of blocking monoclonal
      Abs (mAbs) directed against the costimulatory molecules CD40L, CD80 and CD86,
      alone or in different combinations, on the humoral and cellular immune responses
      against Ad. Groups of mice were transiently treated with each combination of
      blocking mAbs upon systemic injection of a first Ad vector. Combinations of anti
      CD80 + anti-CD86 or anti-CD40L + anti-CD86 mAbs resulted in strong inhibition of
      the immune response against Ad. Using either of these mAb pairs, a second vector
      could be administered 1 month after the first injection but with lower efficiency
      than in naive animals. Thus, CD86 stands as the pivotal B7 molecule involved in
      the development of the immune response against Ad. However, only the blockade of
      both CD80 and CD86 in addition to CD40L fully inhibited the humoral and cellular
      responses against the Ad vector, such that readministration after 1 month was as
      efficient as in naive animals. At the time of readministration, treated animals
      had regained their ability to mount a normal immune response to the second Ad
      vector, showing that tolerance was not induced.

PMID- 11973630
TI  - Human urinary bladder carcinomas express adenovirus attachment and
      internalization receptors.
AB  - The use of adenoviral vectors as potent gene delivery systems requires expression
      of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface.
      This receptor is important for virus attachment to the cell surface. For
      effective internalization of the vector into the target cell the integrins
      alpha(v)beta(3) and/or alpha(v)beta(5) are needed. Since there have been reports
      of loss of CVADR in bladder cancer cell lines, we wanted to investigate the
      expression of this receptor in bladder carcinoma biopsies. Surgical biopsies, as
      well as five human bladder cancer cell lines, were analyzed for expression of
      CVADR, the integrins alpha(v)beta(3) and alpha(v)beta(5) and MHC class I.
      Further, we studied the ability to transduce these cell lines using adenoviral
      vectors. Immunohistochemistry revealed that all biopsies (27/27) were positive
      for CVADR. Some variation in expression was evident, and superficially growing
      tumors stained more strongly than invasive ones. Most human tumors expressed the
      integrin alpha(v)beta(5) (14/24), whereas integrin alpha(v)beta(3) was less
      frequently seen (3/20). The established cell lines were efficiently transduced
      with adenoviral vectors, and transduction could be reduced with anti-CVADR
      antibodies. The abundance of appropriate viral receptors on tumor biopsy cells is
      a further argument for using adenoviral vectors in gene therapy of bladder
      cancer.

PMID- 11973631
TI  - Adeno-associated virus-mediated transfer of human acid maltase gene results in a
      transient reduction of glycogen accumulation in muscle of Japanese quail with
      acid maltase deficiency.
AB  - Glycogen storage disease type II (GSD II), Pompe's disease, is caused by the
      deficiency of acid alpha-D-glucosidase (GAA) in lysosome and is the most common
      form of GSD in Taiwan. Most cases are the infantile form. The disease is
      relentless and most patients die of cardiac failure and respiratory tract
      infection in the first year of life. At present, no treatment has been proved
      effective for this fatal disease. The applicability of enzyme replacement therapy
      is under investigation. However, high price and transient efficiency are the
      major problems to be solved. Accordingly, gene therapy by viral method has been
      conducted. In this study we constructed a plasmid that contained 5'-shortened
      BglII-NotI fragment human GAA cDNA, downstream of CMV promoter and bovine growth
      hormone polyadenylation signal, as well as AAV ITR region. When fibroblasts
      obtained from GSD II patients were cultured and infected with rAAV-GAA, the GAA
      activity of the fibroblasts increased four- to five-fold. Using acid maltase
      deficient (AMD) Japanese quail as the animal model, rcAAV-GAA 0.1 ml per site (1
      x 10(9)-10) particles), totally 10 different sites to make 1 ml (1 x 10(1)0-11)
      particles), was injected into unilateral deep pectoral muscle of AMD quails.
      Medium (hepes) was only injected in the same way into the contralateral deep
      pectoral muscle to serve as control. Four days after injection, PAS staining
      showed disappearance of the glycogenosomes with regeneration of myocytes
      surrounding the intramuscular injected area as compared with the contralateral
      muscle of the same birds. Using anti-GAA monoclonal antibody, GAA was
      demonstrated on the regenerated myocytes by immunohistochemical staining and
      absent on the contralateral muscle of the same birds. Nevertheless, T lymphocytes
      infiltration was noted in both the rcAAV-GAA and hepes (medium) injected muscles
      and more prominent in the rcAAV-GAA-injected site. Functional evaluation
      demonstrated that wing flapping movement improved with wide flapping in the rAAV
      GAA injected side, but not in the counterpart. Unfortunately, these histochemical
      and functional improvements faded away in 14 days, probably due to destruction of
      rcAAV by cell-mediated immunity of infiltrated T cells. Taken together, the
      present study suggests that rAAV can enter either human or quail cells and
      express and effectively reduce the glycogen accumulation in the skeletal muscle
      of AMD quails. These preliminary results are similar to these of low-dose rGAA
      replacement therapy. The mechanisms underlying the induction of cell-mediated
      immunity are unknown. How to elevate the number of packaged AAV, enhance the
      infectivity of AAV and reduce cell-mediated immunity must be solved in the
      future.

PMID- 11973632
TI  - Characterisation of LMD virus-like nanoparticles self-assembled from cationic
      liposomes, adenovirus core peptide mu and plasmid DNA.
AB  - Liposome:mu:DNA (LMD) is a ternary nucleic acid delivery system built around the
      mu peptide associated with the condensed core complex of the adenovirus. LMD is
      prepared by precondensing plasmid DNA (D) with mu peptide (M) in a 1:0.6 (w/w)
      ratio and then combining these mu:DNA (MD) complexes with extruded cationic
      liposomes (L) resulting in a final lipid:mu:DNA ratio of 12:0.6:1 (w/w/w).
      Correct buffer conditions, reagent concentrations and rates of mixing are all
      crucial to success. However, once optimal conditions are established, homogeneous
      LMD particles (120 +/- 30 nm) will result that each appear to comprise an MD
      particle encapsulated within a cationic bilammellar liposome. LMD particles can
      be formulated reproducibly, they are amenable to long-term storage (>1 month) at 
      80 degrees C and are stable to aggregation at a plasmid DNA concentration up to 5
      mg/ml (15 mM nucleotide concentration). Furthermore, LMD transfections are
      significantly more time and dose efficient in vitro than cationic liposome
      plasmid DNA (LD) transfections. Transfection times as short as 10 min and plasmid
      DNA doses as low as 0.001 microg/well result in significant gene expression. LMD
      transfections will also take place in the presence of biological fluids (eg up to
      100% serum) giving 15-25% the level of gene expression observed in the absence of
      serum. Results from confocal microscopy experiments using fluorescent-labelled
      LMD particles suggest that endocytosis is not a significant barrier to LMD
      transfection, although the nuclear membrane still is. We also confirm that
      topical lung transfection in vivo by LMD is at least equal in absolute terms with
      transfection mediated by GL-67:DOPE:DMPE-PEG(5000) (1:2:0.05 m/m/m), an accepted
      'gold-standard' non-viral vector system for topical lung transfection, and is in
      fact at least six-fold more dose efficient. All these features make LMD an
      important new non-viral vector platform system from which to derive tailor-made
      non-viral delivery systems by a process of systematic modular upgrading.

PMID- 11973633
TI  - Gene transfer of Fc-fusion cytokine by in vivo electroporation: application to
      gene therapy for viral myocarditis.
AB  - Among a number of techniques for gene transfer in vivo, the direct injection of
      plasmid DNA into muscle is simple, inexpensive and safe. Although combining
      direct DNA injection with in vivo electroporation increases the efficiency of
      gene transfer into muscle, applications of this method have remained limited
      because of the relatively low expression level. To overcome this problem, we
      developed a plasmid vector that expresses a secretory protein as a fusion protein
      with the noncytolytic immunoglobulin Fc portion and used it for electroporation
      mediated viral interleukin 10 (vIL-10) expression in vivo. The fusion cytokine
      vIL-10/mutFc was successfully expressed and the peak serum concentration of vIL
      10 was almost 100-fold (195 ng/ml) higher than with a non-fusion vIL-10
      expression plasmid. The expressed fusion cytokine suppressed the
      phytohemagglutinin-induced IFN-gamma production by human peripheral blood
      mononuclear cells and decreased the mortality in a mouse viral myocarditis model
      as effectively as vIL-10 expression. These results demonstrate that the transfer
      of plasmid DNA expressing a noncytolytic Fc-fusion cytokine is useful to deliver
      enhanced levels of cytokine without altering general biological activities. This
      simple and efficient system should provide a new approach to gene therapy for
      human diseases and prove very useful for investigating the function of newly
      discovered secretory protein genes.

PMID- 11973634
TI  - Double suicide gene therapy using a replication defective herpes simplex virus
      vector reveals reciprocal interference in a malignant glioma model.
AB  - Herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli cytosine
      deaminase (CD) are non-mammalian enzymes capable of converting innocuous prodrugs
      into cytotoxic metabolites. Both enzymes have been utilized independently, as
      well as together in 'suicide' gene therapy protocols to eliminate tumor cells in
      vitro and in vivo. We have used a set of replication defective HSV vectors
      expressing either or both enzymes to compare the efficacies of single and double
      suicide gene therapies in the 9L gliosarcoma model in vitro and in vivo. In cell
      culture experiments at high and low multiplicities of infection, combined
      expression of the two genes by vector TOCD/TK along with exposure to the matching
      prodrugs (ganciclovir and 5-fluorocytosine) showed increased cytotoxicity
      compared with exposure to either prodrug alone. However, the two gene combination
      was inferior to single gene treatments, suggesting that HSVtk and CD are mutually
      counteractive in the prodrug-dependent killing of glioma cells. In animal
      experiments, survival was not significantly prolonged by administration of both
      prodrugs to TOCD/TK-treated animals, while each single gene/prodrug pair resulted
      in increased survival. These results indicate that single suicide gene systems
      employing HSVtk or CD may be preferable over combinations of the two.

PMID- 11973635
TI  - Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells
      genetically modified with melanoma antigen gp100.
AB  - Lymphotactin (Lptn) is a C chemokine that attracts T cells and NK cells.
      Dendritic cells (DC) are highly efficient, specialized antigen-presenting cells
      and antigen-pulsed DC has been regarded as promising vaccines in cancer
      immunotherapy. The aim of our present study is to improve the therapeutic
      efficacy of DC-based tumor vaccine by increasing the preferential chemotaxis of
      DC to T cells. In this study, Lptn and/or melanoma-associated antigen gp100 were
      transfected into mouse bone marrow-derived DC, which were used as vaccines in B16
      melanoma model. Immunization of C57BL/6 mice with DC adenovirally cotransfected
      with Lptn and gp100 (Lptn/gp100-DC) could enhance the cytotoxicities of CTL and
      NK cells, increase the production of IL-2 and interferon-gamma significantly, as
      compared with immunization with gp100-DC, Lptn-DC, LacZ-DC, DC or PBS
      counterparts. The Lptn/gp100-DC immunized mice exhibited resistance to tumor
      challenge most effectively. It was found that the tumor mass of mice vaccinated
      by Lptn/gp100-DC showed obvious necrosis and inflammatory cell infiltration. In
      vivo depletion analysis demonstrated that CD8(+) T cells are the predominant T
      cell subset responsible for the antitumor effect of Lptn/gp100-DC and CD4(+) T
      cells were necessary in the induction phase of tumor rejection, while NK cells
      were less important although they participated in the antitumor response either
      in the induction phase or in the effector phase. In the murine model with the pre
      established subcutaneous B16 melanoma, immunization with Lptn/gp100-DC inhibited
      the tumor growth most significantly when compared with other counterparts. These
      findings provide a potential strategy to improve the efficacy of DC-based tumor
      vaccines.

PMID- 11973636
TI  - MBP-1 mediated apoptosis involves cytochrome c release from mitochondria.
AB  - MBP-1, a cellular factor, appears to be involved in multiple functions, including
      transcriptional modulation, apoptosis and cell growth regulation. In this study,
      we have investigated the signaling pathway involved in MBP-1 mediated apoptotic
      cell death. Human carcinoma cells infected with a replication deficient
      adenovirus expressing MBP-1 (AdMBP-1) induced apoptosis, when compared with cells
      infected by replication-defective adenovirus (dl312) as a negative control.
      Transduction of MBP-1 in carcinoma cells releases cytochrome c from mitochondria
      into the cytosol leading to activation of procaspase-9, procaspase-3 and PARP
      cleavage. We previously observed that MBP-1 mediated apoptosis can be protected
      by Bcl-2, although MBP-1 does not share a homology with the BH domain of the Bcl
      2 family member of proteins. To further understand the mechanism of MBP-1
      mediated apoptosis, we examined whether MBP-1 modulates the Bcl-2 gene family.
      Our results demonstrated that human breast carcinoma cells infected with AdMBP-1
      selectively reduced Bcl-xL mRNA and protein expression when compared with dl312
      infected negative control cells. An in vitro transient reporter assay also
      suggested repression of the Bcl-x promoter activity by MBP-1. Additional studies
      indicated that MBP-1 modulates Ets family protein function, thereby
      downregulating Bcl-xL expression. Taken together, our results suggest that MBP-1
      selectively represses Bcl-xL expression in MCF-7 cells and induces mitochondrial
      involvement in the apoptotic process.

PMID- 11973637
TI  - Activation of the TGFalpha autocrine loop is downstream of IGF-I receptor
      activation during mitogenesis in growth factor dependent human colon carcinoma
      cells.
AB  - The inappropriate expression of TGFalpha in growth arrest contributes to
      malignant progression in human colon carcinoma cells. Early stage, non-progressed
      colon tumor cells show a down-regulation of TGFalpha in growth arrest and require
      both nutrients and growth factors for re-entry into the cell cycle. In contrast,
      highly progressed cells up-regulate TGFalpha during growth arrest and require
      only nutrients for re-entry. Given the importance of TGFalpha in malignant
      progression, this work addressed the regulation of TGFalpha expression in the
      early stage colon carcinoma cell line, FET. Growth-arrested FET cells down
      regulated the expression of TGFalpha, EGFr and, in turn, EGFr activation. These
      quiescent cells continued to express high levels of IGF-IR protein, but IGF-IR
      activation was undetectable. Cell cycle re-entry required exogenous growth factor
      activation of the IGF-IR by insulin or IGF-I. This IGF-IR activation resulted in
      S phase re-entry and was accompanied by an approximate threefold induction of
      TGFalpha expression along with EGFr activation at 1 h following release from
      growth arrest. Activation of IGF-IR occurred within 5 min of cell-cycle re-entry.
      Previously identified DNA binding proteins which bind to a unique TGFalpha/EGF
      response element within the TGFalpha promoter were similarly induced following
      IGF-IR activation. The addition of EGFr neutralizing antibodies abolished the
      activated IGF-IR stimulated S phase re-entry. Moreover, disruption of the growth
      arrest associated down-regulation of TGFalpha in FET cells by constitutive
      TGFalpha expression abrogated the requirement for IGF-IR activation for cell
      cycle re-entry. Consequently, this study indicates, for the first time, that IGF
      IR activation up-regulates components of the TGFalpha autocrine loop resulting in
      TGFalpha-mediated EGFr activation which was critical for IGF-IR mediated re-entry
      into the cell cycle from the growth-arrested state.

PMID- 11973638
TI  - Decreased susceptibility to NMU-induced mammary carcinogenesis in transgenic rats
      carrying multiple copies of a rat ras gene driven by the rat Harvey ras promoter.
AB  - Ras protein over-expression has been observed in human breast cancers although
      the significance of Ras over-expression in the etiology of breast cancer is
      unknown and its contribution to breast cancer prognosis is still debated. In this
      study, the over-expression of both wild-type Harvey and Kirsten Ras proteins as
      contributors to rat mammary carcinogenesis were examined using a transgenic rat
      model. Three rat transgenic lines (designated HrHr transgenics) carrying three to
      six copies of wild-type rat Harvey ras driven by the wild-type rat Harvey ras
      promoter were produced. In addition, transgenic lines carrying either three or
      seven copies of the Kirsten ras gene under the same promoter (HrKr) were
      produced. No pathological changes in the mammary gland were observed in any of
      the HrHr or HrKr transgenic rat line heterozygotes. Two of the Ras transgenic
      lines, HrHr (R8) and HrKr (4334), had a significant reduction in NMU-induced rat
      mammary cancer when compared to their non-transgenic littermates. All five Ras
      transgenic lines developed fewer carcinomas than their non-transgenic littermates
      following NMU exposure. The percentage of NMU-induced G35 to A35 activating
      mutations in the endogenous Harvey ras gene in mammary carcinomas from the HrHr,
      HrKr transgenic rats and their non-transgenic littermates was similar (
      approximately 50%). In contrast, less than 1% of the NMU-induced carcinomas in
      these Ras transgenic rats had an activating ras mutation in their transgenes.
      These findings highlight the potential of Ras to function as a modifier gene in
      repressing mammary carcinogenesis.

PMID- 11973640
TI  - Adrenomedullin promotes formation of xenografted endometrial tumors by
      stimulation of autocrine growth and angiogenesis.
AB  - The angiogenic peptide adrenomedullin (ADM) has been implicated as a mediator of
      the increased risk of endometrial hyperplasia and cancer resulting from the use
      of tamoxifen for the treatment and prevention of breast cancer. ADM has been
      shown to be induced by tamoxifen in the endometrium and to be a growth factor for
      endometrial endothelial cells in vitro. We have now shown ADM to be strongly
      angiogenic in the mouse subcutaneous sponge angiogenesis assay. To examine the
      role of ADM in tumor growth, the ADM cDNA was transfected into endometrial
      carcinoma cells followed by xenografting into athymic mice. Two endometrial
      cancer cell lines were employed, those in which transfection and expression of
      ADM resulted in no effect on growthin vitro (Ishikawa cells) and those in which
      expressionof exogenous ADM stimulated in vitro growth (RL95.2 cells). A clear
      enhancement of tumor growth was seen with both cell lines but the effect was far
      greater with the RL95.2 cells. We conclude that ADM is pro-tumorigenic by
      stimulating either angiogenesis alone or by stimulating angiogenesis and
      carcinoma cell growth directly. The combined activities lead to a striking
      increase in tumor growth. These results provide the first direct evidence of
      tumorigenic activity of ADM and provide further support for ADMs involvement in
      tamoxifen induced endometrial neoplasia.

PMID- 11973639
TI  - Squalamine and cisplatin block angiogenesis and growth of human ovarian cancer
      cells with or without HER-2 gene overexpression.
AB  - Angiogenesis is important for growth and progression of ovarian cancers.
      Squalamine is a natural antiangiogenic sterol, and its potential role in
      treatment of ovarian cancers with or without standard cisplatin chemotherapy was
      assessed. Since HER-2 gene overexpression is associated with cisplatin resistance
      in vitro and promotion of tumor angiogenesis in vivo, the response of ovarian
      cancer cells with or without HER-2 gene overexpression to squalamine and
      cisplatin was evaluated both in tumor xenograft models and in tissue culture.
      Ovarian cancer cells with or without HER-2 overexpression were grown as
      subcutaneous xenografts in nude mice. Animals were treated by intraperitoneal
      injection with control vehicle, cisplatin, squalamine or cisplatin combined with
      squalamine. At the end of the experiment, tumors were assessed for tumor growth
      inhibition and for changes in microvessel density and apoptosis. Additional in
      vitro studies evaluated effects of squalamine on tumor and endothelial cell
      growth and on signaling pathways in human endothelial cells. Profound growth
      inhibition was elicited by squalamine alone and by combined treatment with
      squalamine and cisplatin for both parental and HER-2-overexpressing ovarian tumor
      xenografts. Immunohistochemical evaluation of tumors revealed decreased
      microvessel density and increased apoptosis. Although HER-2-overexpressing tumors
      had more angiogenic and less apoptotic activity than parental cancers, growth of
      both tumor types was similarly suppressed by treatment with squalamine combined
      with cisplatin. In in vitro studies, we found that squalamine does not directly
      affect proliferation of ovarian cells. However, squalamine significantly blocked
      VEGF-induced activation of MAP kinase and cell proliferation in human vascular
      endothelial cells. The results suggest that squalamine is anti-angiogenic for
      ovarian cancer xenografts and appears to enhance cytotoxic effects of cisplatin
      chemotherapy independent of HER-2 tumor status.

PMID- 11973641
TI  - Significant up-regulation of a novel gene, CLCP1, in a highly metastatic lung
      cancer subline as well as in lung cancers in vivo.
AB  - Most lung cancer patients are unfortunately uncurable and die because of
      widespread metastases, thus indicating the importance of identification of
      molecules with a crucial role in this process. Our previous expression profiling
      analysis of a highly metastatic lung cancer cell line, NCI-H460-LNM35, and its
      parental low metastatic line, NCI-H460-N15, revealed significant up-regulation of
      both known and unknown genes in LNM35. In this study, we describe the isolation
      and detailed characterizations of a novel gene, named CLCP1, which corresponds to
      one of such expression sequence tags with up-regulated expression in LNM35. The
      CLCP1 gene was found to encode a protein with 775 amino acids with structural
      similarities to, but distinct from neuropilins, cell surface receptors for
      VEGF165 and semaphorins. Notably, CLCP1 was shown to be up-regulated not only in
      LNM35 in association with its acquisition of metastatic phenotype during in vivo
      selection, but also in a significant fraction of lung cancers in vivo with high
      frequency in metastatic lesions, warranting future studies for a better
      understanding of the molecular mechanisms of lung cancer metastasis.

PMID- 11973642
TI  - The class II tumour suppressor gene H-REV107-1 is a target of interferon
      regulatory factor-1 and is involved in IFNgamma-induced cell death in human
      ovarian carcinoma cells.
AB  - H-rev107-1 is a growth inhibitory RAS target gene capable of suppressing
      anchorage independent growth in vitro and in vivo. Using a tumour tissue array
      with 241 matched tumour and normal tissue cDNA pools, we found down-regulation of
      H-REV107-1 in 7 out of 14 ovary-derived cDNAs. RT-PCR analysis and
      immunohistochemical investigation confirmed expression of H-REV107-1 in normal
      ovarian epithelial cells but down-regulation in high grade ovarian carcinomas. H
      REV107-1 is also strongly expressed in immortalized rat and human ovarian
      epithelial cells in vitro, but suppressed in transformed cells by two different
      mechanisms. KRAS-transformed rat ovarian cells and PA1 teratocarcinoma cells,
      reversibly repress H-REV107-1 via MAP/ERK signaling. In contrast, treatment of
      A27/80 and OVCAR-3 epithelial ovarian cancer cells with IFNgamma stimulated H
      REV107-1 expression. In NIH3T3 cells harbouring an estrogen-inducible IRF-1, H
      rev107-1 is directly induced after activation of IRF-1, indicating that H-rev107
      1 is a target of IRF-1. Stimulation of H-REV107-1 expression was also observed in
      ovarian epithelial cells suggesting that IRF-1 is involved in H-REV107-1
      regulation in human ovarian epithelium. In the IFNgamma-sensitive cell line
      A27/80, H-REV107-1 suppresses colony formation. A27/80 and OVCAR-3 cells
      overexpressing H-REV107-1 protein underwent apoptosis. These results demonstrate
      down-regulation of the class II tumour suppressor H-REV107-1 in human ovarian
      carcinomas and suggest an involvement of H-REV107-1 in interferon-dependent cell
      death.

PMID- 11973643
TI  - Loss of heterozygosity and point mutation at Aprt locus in T cells and
      fibroblasts of Pms2-/- mice.
AB  - Mice null for the Pms2 mismatch repair (MMR) gene exhibit a predisposition to
      lymphoma, microsatellite repeat instability, and failure of spermatogenesis. To
      study the role of Pms2 in the maintenance of in vivo genomic integrity in somatic
      cells, we characterized Aprt mutations in T cells and fibroblasts of 129 x C3H
      Pms2-/-Aprt+/- mice. The spontaneous frequency of DAP-resistant T lymphocytes, as
      a consequence of APRT-deficiency, was increased threefold. Point mutation, which
      accounted for less than 20% of the DAP(r) mutant clones in Pms2+/+ mice, was
      predominant in the mutant T cell clones from Pms2-/- mice. These point mutations
      were predominantly TA to CG transitions. Fibroblasts of Pms2-/- mice exhibited
      only a modest increase in the frequency of clones with point mutations, such that
      mitotic recombination was still the primary cause of APRT deficiency. Thus, the
      mutator phenotype as a consequence of PMS2 deficiency is tissue-dependent, which
      may be related to the tissue-specific tumor proneness of Pms2-/- mice.

PMID- 11973644
TI  - Differential function of STAT5 isoforms in head and neck cancer growth control.
AB  - Up-regulation of the epidermal growth factor receptor (EGFR) is critical for the
      loss of growth control in a variety of human cancers, including squamous cell
      carcinoma of the head and neck (SCCHN). Stimulation of EGFR results in activation
      of mitogenic signaling pathways including Signal Transducers and Activators of
      Transcription (STATs). Stat5 activation has been primarily demonstrated in
      hematopoietic malignancies. Gene disruption studies suggest potentially distinct
      functions of the Stat5 isoforms, Stat5a and Stat5b, which are encoded by two
      genes closely linked on human chromosome 17. To determine the function of Stat5
      in SCCHN growth control, we studied the expression and constitutive activation of
      Stat5a and Stat5b in normal and transformed human squamous epithelial cells.
      Increased constitutive activation of Stat5 was detected in transformed compared
      with normal squamous cells. Blockade of TGF-alpha or EGFR, abrogated Stat5
      activation. Targeting of Stat5b using antisense oligonucleotides inhibited SCCHN
      growth. In addition, SCCHN cells stably transfected with dominant negative mutant
      Stat5b failed to proliferate in vitro. In contrast, targeting of Stat5a using
      either antisense or dominant negative strategies had no effect on cell growth.
      These results suggest that TGF-alpha/EGFR-mediated autocrine growth of
      transformed epithelial cells is dependent on activation of Stat5b but not Stat5a.

PMID- 11973646
TI  - The v-erbA oncogene blocks expression of alpha2/beta1 integrin a normal inhibitor
      of erythroid progenitor proliferation.
AB  - T2EC are chicken erythrocytic progenitors that balance between self-renewal and
      differentiation as a function of response to specific growth factors. Their
      transformation by the v-erbA oncogene locks them into the self-renewal program.
      We show here that the expression of the VLA-2 integrin alpha2 subunit mRNA is
      downregulated by v-erbA and that VLA-2 engagement and clustering, brought about
      by treatment with an alpha2-specific antibody or by culture on the VLA-2 ligand
      collagen I, inhibits T2EC proliferation. From competition studies using
      antibodies, VLA-2 was shown to be involved in the collagen-induced response.
      While engagement of VLA-2 inhibited proliferation, it was not sufficient to
      induce differentiation. The transformation of T2EC by v-erbA decreased their
      interaction with collagen I and the VLA-2 brake on cell proliferation, which may
      account for the increased proliferation potential of transformed erythrocytic
      progenitors and for their shedding into the blood of infected chickens. Our data
      suggest that the interaction between erythroid progenitors and collagen, mediated
      by VLA-2, play a major role in the control of erythropoiesis in vitro and that
      this pathway is a target of the v-erbA oncogene.

PMID- 11973645
TI  - Regulation of aromatase promoter activity in human breast tissue by nuclear
      receptors.
AB  - Using the yeast one-hybrid approach to screen a human breast tissue hybrid cDNA
      expression library, we have found that four orphan/nuclear receptors, ERRalpha-1,
      EAR-2, COUP-TFI (EAR-3), and RARgamma, bind to the silencer (S1) region of the
      human aromatase gene. S1 down regulates promoters I.3 and II of the human
      aromatase gene. In this study, the interaction of EAR-2, COUP-TFI, and RARgamma
      with S1 was confirmed by DNA mobility shift analysis. In contrast to the findings
      that ERRalpha-1 behaves as a positive regulatory factor, these three nuclear
      receptors were found, by mammalian cell transfection experiments, to act as
      negative regulatory factors by binding to S1. Furthermore, the negative action of
      these three nuclear receptors could override the positive effect of ERRalpha-1.
      RT-PCR analysis of 11 cell lines and 55 human breast tumor specimens has shown
      that these nuclear receptors are expressed in human breast tissue. Since EAR-2,
      COUP-TFI, and RARgamma are expressed at high levels, it is likely that S1 is a
      negative regulatory element that suppresses aromatase promoters I.3 and II in
      normal breast tissue. In cancer tissue, S1 may function as a positive element
      since ERRalpha-1 is expressed, but EAR-2 and RARgamma are only present in a small
      number of tumor specimens. This hypothesis is sustained by the finding that there
      is a weak inverse correlation between the expression of COUP-TFI and that of
      aromatase in breast tumor tissue. Our studies have revealed that estrogen
      receptor alpha (ERalpha) can also bind to S1, in a ligand-dependent manner. By
      binding to S1, ERalpha down-regulates the aromatase promoter activity. These
      results demonstrate that nuclear receptors play important roles in modulating
      aromatase expression in human breast tissue.

PMID- 11973647
TI  - Methylation tolerance in mismatch repair proficient cells with low MSH2 protein
      level.
AB  - Loss of DNA mismatch repair has been found in tumors associated with the familial
      cancer predisposition syndrome HNPCC (hereditary non-polyposis colorectal cancer)
      and a subset of sporadic cancers. MSH2 deficiency abolishes the action of the
      mismatch repair system, resulting in a phenotype which is characterized by an
      increased accumulation of base substitutions and frameshifts, enhanced
      recombination between homologous but non-identical DNA sequences, and tolerance
      to the cytotoxic effects of methylating agents. In this study we describe an
      embryonic stem cell line in which the level of MSH2 protein is 10-fold reduced
      compared to that in wild-type cells. Remarkably, these MSH2-low cells were as
      resistant to killing by methylating agents as cells completely lacking MSH2,
      while they had retained almost maximal mismatch repair capacity as judged from
      their anti-mutagenic and anti-recombinogenic capacity and the absence of
      microsatellite instability. In contrast, MSH2-low cells were highly sensitive to
      methylation-damage induced mutagenesis. Thus, 10-fold reduced MSH2 protein levels
      render cells resistant to the toxic and highly sensitive to the mutagenic effects
      of methylating agents. This condition is not manifested by microsatellite
      instability and may have implications for both the etiology and treatment of
      cancer.

PMID- 11973648
TI  - Developmentally-related candidate retinoic acid target genes regulated early
      during neuronal differentiation of human embryonal carcinoma.
AB  - Embryonal carcinoma is a model of embryonic development as well as tumor cell
      differentiation. In response to all-trans retinoic acid (RA), the human embryonal
      carcinoma (EC) cell line, NT2/D1, differentiates toward a neuronal lineage with
      associated loss of cell growth and tumorigenicity. Through the use of cDNA-based
      microarrays we sought to identify the early downstream targets of RA during
      differentiation commitment of NT2/D1 cells. A total of 57 genes were induced and
      37 genes repressed by RA. RA regulated genes were restricted at 8 h with 27 genes
      induced and five repressed. The total number of RA-responsive transcripts
      increased at 24 and 48 h and their pattern of expression was more symmetrical.
      For a given time point less than 1% of the 9128 cDNAs on the expression array
      were regulated by RA. Many of these gene products are associated with
      developmental pathways including those of TGF-beta (Lefty A, NMA, follistatin),
      homeo domain (HoxD1, Meis2, Meis1, Gbx2), IGF (IGFBP3, IGFBP6, CTGF), Notch
      (manic fringe, ADAM11), Hedgehog (patched) and Wnt (Frat2, secreted frizzled
      related protein 1) signaling. In addition a large cassette of genes induced by RA
      at 24-48 h are associated with cell adhesion, cytoskeletal and matrix remodeling,
      growth suppression and intracellular signaling cascades. The majority of
      repressed genes are associated with protein/RNA processing, turnover or
      metabolism. The early induced genes identified may play a regulatory role in RA
      mediated growth suppression and terminal differentiation and may have physiologic
      or pharmacologic importance during normal human development and retinoid-based
      cancer therapy or prevention.

PMID- 11973649
TI  - Differential regulation of the response to DNA damage in Ewing's sarcoma cells by
      ETS1 and EWS/FLI-1.
AB  - Ewing's sarcoma (EWS) cells contain levels of poly(ADP-ribose) polymerase (PARP)
      significantly higher than other eukaryotic cells. Previously, we cloned the PARP
      gene promoter region from EWS cells, showed that it contained multiple ETS
      binding sites and demonstrated a positive regulation of PARP by ETS1. We now
      report that, contrary to ETS1, EWS/FLI-1, an aberrant ETS transcription factor
      present in most EWS cells, is a negative effector of PARP transcription. Because
      PARP levels have been associated with cellular resistance or sensitivity to
      genotoxic agents, we studied the effect of modifying PARP levels in EWS cells on
      their response to DNA damage by modulating the expression of ETS1 or EWS/FLI-1
      using antisense methodology. Results show that stable down-regulation of ETS1
      increases the resistance of EWS cells to various genotoxic agents, whereas down
      regulation of EWS/FLI-1 has pro-apoptotic effects. Because down-regulation
      EWS/FLI-1 does not dramatically change PARP levels, these results suggest a
      direct effect for EWS/FLI-1 in the DNA damage response of EWS cells. Since
      expression of the aberrant fusion proteins by EWS cells is essential for
      maintaining their neoplastic phenotype, our results suggest that the use of
      antisense oligonucleotides in combination with chemotherapeutic agents or
      radiation may be doubly effective by causing both an increase in sensitivity to
      therapeutic agents and a simultaneous down-regulation, or reversion, of the
      neoplastic phenotype of EWS cells.

PMID- 11973650
TI  - Enhanced expression of vascular endothelial growth factor (VEGF) plays a critical
      role in the tumor progression potential induced by simian virus 40 large T
      antigen.
AB  - Vascular endothelial growth factor (VEGF), an important angiogenic factor,
      regulates cell proliferation, differentiation, and apoptosis through activation
      of its tyrosine-kinase receptors, such as Flt-1 and Flk-1/Kdr. Human malignant
      mesothelioma cells (HMC), which have wild-type p53, express VEGF and exhibit cell
      growth increased by VEGF. Here, we demonstrate that early transforming proteins
      of simian virus (SV) 40, large tumor antigen (Tag) and small tumor antigen (tag),
      which have been associated with mesotheliomas, enhanced HMC proliferation by
      inducing VEGF expression. SV40-Tag expression potently increased VEGF protein and
      mRNA levels in several HMC lines. This effect was suppressed by the protein
      synthesis inhibitor, cycloheximide. Inactivation of the VEGF signal transduction
      pathway by expression of soluble form of Flt-1 inhibited Flk-1/Kdr activation and
      HMC proliferation induced by SV40 early genes. Experiments with SV40 mutants
      revealed that SV40-Tag, but not -tag, is involved in the VEGF promoter
      activation. However, concomitant expression of SV40-tag enhanced Tag function. In
      addition, SV40-Tag expression sustained VEGF induction in colon carcinoma cell
      line (CCL)-233, which have wild-type p53, but not in CCL-238, which lack
      functional p53. These data indicate that VEGF regulation by SV40 transforming
      proteins can represent a key event in SV40 signaling relevant for tumor
      progression.

PMID- 11973651
TI  - Participation of small GTPases Rac1 and Cdc42Hs in myoblast transformation.
AB  - We have previously shown that expression of active Rac1 and Cdc4Hs inhibits
      skeletal muscle cell differentiation. We show here, by bromodeoxyuridine
      incorporation and cyclin D1 expression, that the expression of active Rac1 and
      Cdc42Hs but not RhoA impairs cell cycle exit of L6 myoblasts cultured in
      differentiation medium. Furthermore, expression of activated forms of Rac1 and
      Cdc42Hs elicits the loss of cell contact inhibition and anchorage-dependent
      growth as measured by focus forming activity and growth in soft agar. RhoA was
      once again not found to have this effect. We found a constitutive Rac1 and
      Cdc42Hs activation in three human rhabdomyosarcoma-derived cell lines, one of the
      most common causes of solid tumours arising from muscle precursors during
      childhood. Finally, dominant negative forms of Rac1 and Cdc42Hs inhibit cell
      proliferation of the RD rhabdomyosarcoma cell line. These data suggest an
      important role for the small GTPases Rac1 and Cdc42Hs in the generation of
      skeletal muscle tumours.

PMID- 11973652
TI  - Increased Bcl-xL expression mediates v-Src-induced resistance to anoikis in
      intestinal epithelial cells.
AB  - Acquisition of resistance to anoikis (detachment-induced apoptosis) is considered
      to be a requirement for transformed intestinal epithelial cells to invade
      surrounding tissues and metastasize to distant organs. Increased Src kinase
      activity, which is a feature of a large proportion of colorectal cancers, has
      been identified as one of the factors that can contribute to anoikis resistance.
      However, the molecular mechanism by which high levels of Src activity contribute
      to anoikis resistance in intestinal epithelial cells is unknown. Here we show
      that high Src activity confers resistance to anoikis in intestinal epithelial
      cells, at least in part, by inducing Bcl-xL overexpression, and that this
      induction is mediated by the MEK/MAPK pathway. Based on the findings reported
      here, and on our previous study showing that Bcl-xL plays a critical role in ras
      induced resistance to anoikis, we propose that the increased Bcl-xL levels found
      in colorectal cancers play a significant role in the induction of resistance to
      anoikis during the progression of this disease.

PMID- 11973653
TI  - Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct
      target for p53.
AB  - Interferon regulatory factors (IRFs) regulate transcription of interferon genes
      through DNA sequence-specific binding to these targets. Using a differential
      display method for examining gene expression in p53-defective cells infected with
      adenovirus containing wild-type p53, we found that expression of interferon
      regulatory factor 5 (IRF-5) mRNA was increased in the presence of exogenous p53.
      An electrophoretic mobility-shift assay showed that a potential p53 binding site
      (p53BS) detected in exon 2 of the IRF-5 gene could in fact bind to p53 protein.
      Moreover, a heterologous reporter assay revealed that the p53BS possessed p53
      dependent transcriptional activity. Expression of IRF-5 was induced in p53+/+
      cells (MCF7 and NHDF), but not inp53-/- cells (H1299) when DNA was damaged by
      gamma-irradiation, UV-radiation, or adriamycin treatment in a wild-type p53
      dependent manner. These results suggest that IRF-5 is a novel p53-target, and
      that it might mediate the p53-dependent immune response.

PMID- 11973654
TI  - Inactivating mutations of the caspase-10 gene in gastric cancer.
AB  - We have analysed the genetic alteration of the entire coding region and all
      splice sites of caspase-8 and -10 genes in 99 gastric cancers by polymerase chain
      reaction (PCR)-single strand conformation polymorphism (SSCP) and sequencing. We
      found LOH of the caspase-8 and -10 in nine (28%) of 32 and in four (15%) of 26
      informative cases, respectively. Overall, three of 99 gastric cancers (3%) were
      found to have the caspase-10 mutations, which were identified in the coding
      regions of the death effector domain (codon 147) and the p17 large protease
      domain (codons 257 and 410), whereas no mutation was detected in caspase-8. In
      vitro expression studies, the M147T and Q257stop mutants severely impaired
      caspase-10-mediated apoptosis, whereas the V410I which was the same mutation
      detected in ALPS patient had a significant, albeit less severe, effect on
      apoptosis. The data presented here suggest that somatic alterations of the
      caspase-10 gene might contribute to the pathogenesis in a subset of gastric
      cancers through the loss of their apoptotic function.

PMID- 11973656
TI  - Posterior lamellar keratoplasty.

PMID- 11973655
TI  - Identification, using cDNA macroarray analysis, of distinct gene expression
      profiles associated with pathological and virological features of hepatocellular
      carcinoma.
AB  - It is still unclear as to whether the gene expression profile in HCV- or HBV
      related HCC exhibits a degree of specificity and whether the development of HCC
      in a context of cirrhosis influences this gene profile. To address these issues,
      the expression profiles of 15 cases of HCC were analysed using cDNA macroarray. A
      global analysis and hierarchical clustering, demonstrated the heterogeneity of
      HCC patterns, with a majority of down-regulated genes. Statistical analysis
      clearly showed a distinction between the gene expression profiles of HCV- and HBV
      related HCC. HBV-associated HCC exhibited involvement of different cellular
      pathways, those controlling apoptosis, p53 signalling and G1/S transition. In HCV
      related HCC we identified a more heterogenous pattern with an over-expression of
      the TGF-beta induced gene. In HCC developing on non-cirrhotic tissues, beta
      catenin encoding gene and genes implicated in the PKC pathway were specifically
      up-regulated. In addition, our investigation highlighted a distinct profiles of
      TGF-beta superfamily encoding genes in well, moderately or poorly differentiated
      HCC. Overall, our study supports the hypothesis that despite the heterogeneity of
      the HCC pattern, the large-scale screening of gene expression may provide data
      significant to our understanding of the mechanism of liver carcinogenesis.

PMID- 11973657
TI  - [Neuro-ophthalmology in mitochondrial disorders].

PMID- 11973658
TI  - [Vogt-Koyanagi-Harada syndrome].

PMID- 11973659
TI  - [Approach to the patient with acute anterior uveitis].
AB  - Uveitis refers to inflammation of the uveal tract, which includes the iris,
      ciliary body, and choroid. Common usage has expanded this definition, however, to
      include intraocular inflammation of any type. Hence, retinitis, retinal
      vasculitis, and papillitis are also grouped under uveitis, even in the absence of
      significant uveal tract inflammation. Uveitis can also be secondary to corneal,
      scleral, or orbital inflammation. Experience has shown that identifying the
      primary focus of intraocular inflammation is important, both for establishing a
      diagnosis and as a predictor of natural history and response to therapy. A number
      of ocular and systemic syndromes are recognized to cause anterior uveitis. Clues
      to the diagnosis of the more commonly encountered anterior uveitis syndromes are
      outlined below. It is important to pay particular attention to the severity of
      the anterior chamber inflammation, and to note the presence of anterior
      granulomatous findings since the intensity and character of the inflammation can
      sometimes suggest a diagnosis.

PMID- 11973660
TI  - [Follow-up of macrotrabeculectomy in glaucoma].
AB  - PURPOSE: In this study we report the preliminary results of macrotrabeculectomy
      in our hospital. METHOD: Fifty-nine eyes of 41 patients with open-angle glaucoma
      underwent macrotrabeculectomy from Sept. 1994 through Sept. 1995 and were
      retrospectively analysed. Intraocular pressure control was defined as a decrease
      of postoperative IOP lower than 21 mm Hg or a decrease of at least 20% of initial
      IOP if this was lower than 21 mm Hg. Disc/cup ratio control was assumed when the
      progression was under 0.2. Disease control was defined when IOP, disc/cup ratio
      and visual field were controlled. RESULTS: IOP control was obtained in 93.22% of
      patients at 2 years and in 91.19% at 3 and 4 years. Disease control was achieved
      in 88.14% at 2 years and 84.3% at 3 and 4 years (Kapplan-Meier survival
      analysis). CONCLUSION: Macrotrabeculectomy is a safe and effective technique to
      control IOP and glaucomatous disease.

PMID- 11973661
TI  - [Vitrectomy for asteroid hyalosis].
AB  - PURPOSE: To evaluate the role of pars plana vitrectomy for asteroid hyalosis and
      synchisys scintillans with decrease of visual acuity. METHODS: Retrospective
      study of 15 patients on whom pars plana vitrectomy was performed. We studied the
      visual acuity before the surgery, the best and the final vision. Risk vascular
      factors, intraocular pressure, complications during the surgery or in the follow
      up were determined. RESULTS: We operated on 17 eyes of 15 patients (10 male, 5
      female). In 2 cases we added peeling of macular pucker and in two cases a
      cataract surgery. Average age was 73.8 (standard deviation 8.6); risk vascular
      factors were found in 66.6%. There weren't any complications during the surgery.
      Later, 4 cataracts, 3 macular pucker and 1 macular hole (stage IV) developed. The
      average vision before the surgery was 20/60, the best 20/40 and the final vision
      20/50. Average follow up time was 22.8 (s.d. 17.3) months. CONCLUSIONS: Asteroid
      hialosis was more frequent in elderly males (2/3) and in patients with risk
      vascular factors (66.6%). Cataract surgery was necessary in 50% of eyes during or
      after the pars plana vitrectomy. Seventeen percent of eyes presented macular
      pucker in the follow up. Recovery of vision was less than expected.

PMID- 11973662
TI  - [Study on hypotensive effect of latanoprost vs timolol-dorzolamide association].
AB  - PURPOSE: To compare hypotensive effect of latanoprost versus timolol-dorzolamide
      association on patients with glaucoma. MATERIAL AND METHOD: We studied 102 eyes
      in 52 patients with intraocular pressure (IOP) higher than 21 mmHg, previously
      treated with a betablocker. Patients were divided in two groups. Treatment was
      changed on group 1 (51 eyes in 27 patients) to a timolol-dorzolamide association.
      Group 2 (51 eyes in 27 patients) changed treatment to latanoprost. After
      determination of previous IOP, readings were taken at 1, 3 and 8 months later.
      RESULTS: Both groups showed a decrease in IOP levels: Group 1, 5.6 mmHg and Group
      2, 8.5 mmHg. Association between timolol and dorzolamide reached the highest
      hypotensive effect after the first month of treatment and remained constant
      during the rest of the study period. Latanoprost showed a maximal effect after
      the third month of treatment and maintained its effect all through the study as
      well. Latanoprost behaved similar to associated timolol-dorzolamide not showing
      significant differences during the first month of treatment. Significant
      differences appeared at third and eighth month favoring latanoprost (p<0.005 and
      p<0.001 respectively). CONCLUSION: There was a similarity in efficacy of both
      treatments. However, after the third month latanoprost became more effective than
      the timolol-dorzolamide association.

PMID- 11973663
TI  - [Transient band keratopathy associated with hypercalcemia].
AB  - PURPOSE: Band keratopathy is a corneal degenerative disease that can produce
      reduced visual acuity. Different ethiogical mechanisms are described, associated
      with ocular or systemic diseases, and treatments like EDTA, lamellar keratoplasty
      and excimer laser photokeratectomy. We report a male with band keratopathy and
      increased calcic serum that decreased after treatment. CONCLUSIONS: Our patient's
      clinical course exemplified the importance of considering systemic causes in band
      keratopathy, and further that the correction of calcium levels can be undertaken
      before other more aggressive treatments.

PMID- 11973664
TI  - [Chronic granulomatous endophthalmitis. Clinical-pathological correlation].
AB  - CASE REPORT: The authors present the case of a patient with a painful eye
      secondary to a non-perforating traumatism sustained in the past which, at the
      time of the injury, had caused a post-traumatic cataract, corneal lesions and a
      secondary glaucoma. The structural damage of the ocular content, associated with
      a well preserved size and external shape, made the diagnosis more difficult,
      requiring additional diagnostic methods. The pathological findings are also
      presented. DISCUSSION: The authors present the available diagnostic methods for
      those cases with chronic inflammation in which direct examination of the ocular
      content is not feasible, and it is mandatory to exclude vital threatening
      pathologies.

PMID- 11973665
TI  - [Nasolacrimal stent: modifications to Ho-Young Song's technique].
AB  - PURPOSE: To introduce modifications to Song's technique in the treatment of
      nasolacrimal occlusion by means of a polyuretane stent. MATERIAL AND METHOD:
      Thirty five polyuretane stents were placed under fluoroscopic guidance in 32
      patients diagnosed with total and partial nasolacrimal occlusion. CONCLUSION:
      Technical success rate was 90%. Sixteen right and nineteen left nasolacrimal
      systems were probed. The introduction of a guidewire through the lower punctum,
      the use of a Ritleng guide, a Crawford hook and ocular protectors are
      modifications of Song's procedure that may help in successfully performing this
      technique in a fast and easy way.

PMID- 11973667
TI  - [Why should the terms "nyctalopia" and "hemeralopia" be avoided?].

PMID- 11973666
TI  - [Congenital Horner's syndrome associated to varicella].
AB  - CASE REPORT: We present a case of congenital Horner's Syndrome in a four year-old
      boy. The patient was referred from the Dermatology ward after a check up for
      malformations present from birth on the left upper limb. A significant factor was
      determined: a varicella related infection in the mother during the 12th week of
      pregnancy. Blood tests confirmed a diagnosis of congenital varicella syndrome.
      DISCUSSION: Congenital Horner's Syndrome is a rare entity, caused mainly by
      traumatic deliveries. Very rarely it is produced by severe lesions, such as
      neuroblastoma or viral infections as varicella. In our case, condition was
      associated to ipsilateral malformations of the upper limb, which is typical from
      congenital varicella syndrome apparently due to radiculopathy produced by the
      virus.

PMID- 11973669
TI  - [Heparin-induced thrombocytopenia type II].

PMID- 11973671
TI  - [Management of HIT II patients with hirudin antibodies after primary therapy].

PMID- 11973670
TI  - [Anticoagulation for HIT II: When should it be used therapeutically and when as
      prophylaxis?].

PMID- 11973672
TI  - [Development of an HPLC method for the diagnosis of heparin-induced
      thrombocytopenia].

PMID- 11973673
TI  - [Anticoagulation in patients with suspected HIT II and acute renal failure].

PMID- 11973674
TI  - [Case report on therapy for HIT II from an assessor's point of view].

PMID- 11973675
TI  - [HIT II in the intensive care unit].

PMID- 11973676
TI  - [Current problems in alternative anticoagulation therapy for HIT II patients].

PMID- 11973677
TI  - [Vestibular diagnostics in childhood - methods and assessment].
AB  - BACKGROUND: Children with vertigo are thought to be difficult to examine.
      Vestibular test batteries are used less frequently for children than in adult
      patients. METHODS: Within the context of a retrospective study 136 patients in
      age between 0 and 15 years, who were examined by Frenzel's glasses, ENG and VOG
      between 1996 and 1999 were evaluated. Caloric test and frequency selective
      rotation chair tests were performed. RESULTS: Workability of VOG examination (91
      %) was higher than Frenzel glasses (86 %) and ENG (78 %). Videooculography is the
      method of choice in childhood. Comparing diagnosis after vestibular testing and
      discharge diagnosis a sensitivity of 68 %, a specificity of 88 %, an accuracy of
      aim of 79 % and a positive predictive value of 92,9 % was calculated. CONCLUSION:
      Thus restriction of vestibular functional diagnostics in childhood is not
      justified.

PMID- 11973678
TI  - [The "Costen Syndrome" - Which Symptoms Suggest that the Patient may Benefit from
      Dental Therapy?].
AB  - INTRODUCTION: Since the thirties the hypothesis of a direct connection between
      temporomandibular disorders (TMD) and tinnitus/otalgia has been discussed. The
      thesis of this possible connection is often named after one of the earliest and
      most vehement supporters as "Costen Syndrome". This review is aimed to elucidate
      the present state of the discussion from the Dentist's point of view.
      DIAGNOSIS/EPIDEMIOLOGY/THERAPY OF TMD: Diagnostic research criteria which define
      TMD are not standardized. Despite high prevalence and strong demand for treatment
      of TMD there is still a lack of a commonly accepted standard therapy and the
      potential benefit from a therapeutic point of view is still controversial. TMD
      AND TINNITUS/OTALGIA:: Concurrence of TMD and tinnitus by a common underlying
      cause is still unproven. By contrast a causal link between certain forms of TMD
      and otalgia is obvious. CONCLUSION: A lack of clear definitions and standards for
      the diagnosis of TMD is the main hinderance to prove a causal relationship
      especially between TMD otalgia. However patients seeking care for otalgia with no
      identifiable otologic cause may benefit from dental therapy. Therefore future
      studies should focus on well defined subgroups of TMD to investigate a link
      between otalgia/tinnitus and TMD.

PMID- 11973679
TI  - [First findings about the nasal airflow in noses with septal perforation].
AB  - BACKGROUND: A nasal septum perforation often leads to considerable complaints
      like nasal obstruction, crusting, epistaxis or whistling. Up to now there is no
      certain knowledge about the airflow pattern in noses with septal perforations.
      METHOD: We performed fluid dynamic experiments on functional nasal models (so
      called modified Mink boxes). We investigated the flow pattern in models with
      septal perforations, different in size and location and in combination with and
      without septal deviations. RESULTS AND CONCLUSIONS: We have found no essential
      influence of the location of perforation on the airflow pattern. With increasing
      size of perforation the streamlines bump toward the posterior border of the
      perforation, causing turbulence. The whistling during inspiration is based on the
      principle of a lip whistle. The required flow velocity for vibration of the air
      depends on the dimension of the perforation. For large perforations it is
      impossible to get the required high flow velocity to cause a whistle.

PMID- 11973681
TI  - [Interdisciplinary endoscopic outpatient management of connatal
      dacryocystoceles].
AB  - Dacryocystocele may represent a rare type of connatal stenosis of the lacrimal
      duct. If conservative measures fail and in case of secondary inflammation,
      probing or regular surgery is usually recommended. We report on 15 neonates
      suffering from 18 connatal dacryocystoceles which were presented to the clinic of
      ophthalmology at the 16th (6 - 44) day of life. There was a definite female
      preponderance (65 %). Conservative treatment (external massage, at times i. v.
      antibiotic therapy) had proven to be ineffective. The neonates were subjected to
      outpatient nasal endoscopy and the ballooning cyst of the inferior nasal meatus
      was managed by endoscopic marsupialization in 14 cases applying local anesthesia.
      Two nasal cysts had to be operated on in general anesthesia due to obstructing
      local anatomy which obviated endoscopical microsurgery. Three additional
      dacryocystoceles have been detected incidentally in 2 neonates being subjected to
      surgery in general anesthesia for choanal atresia and lacrimal probing
      respectively. The corresponding dacryocystoceles were managed by concomitant
      endonasal microsurgery. We advocate interdisciplinary (ophthalmological and
      rhinological) outpatient examination in all neonates with suspected
      dacryocystoceles. Diagnosis is based on palpation, probing and nasal endoscopy
      applying local anesthesia together with mucosal decongestion. Microsurgical
      marsupialization immediately follows and will lead to persisting relief of
      symptoms.

PMID- 11973680
TI  - [Aetiology of Angiofibromas: Reflection on their Specific Vascular Component].
AB  - BACKGROUND: Even though numerous theories have speculated either on the vascular
      or fibrous tumour component as tissue of origin, aetiology of angiofibroma still
      remain unclear. Histological investigations recently led Beham and coworkers to
      the assumption that angiofibromas have to be considered as vascular
      malformations. METHODS: After giving a literature review of the various theories
      on tumour origin the proposal to consider angiofibromas as vascular malformations
      is discussed on an embryological base. Taking typical clinical features of the
      tumour and knowledge of vasculogenesis into account a new explanation for origin
      of the vascular tumour component is presented. RESULTS: The vascular component of
      angiofibromas can be explained embryologically due to incomplete regression of
      the first branchial arch artery (vascular atavism). This vessel arises regularly
      between embryological day 22 and 24 and recedes during regular development
      completely until delivery via temporary formation of a vascular plexus. In the
      late stages of embryological development remnants of the plexus are found at the
      area of the sphenopalatine foramen, the typical site of angiofibroma origin.
      Incomplete regression of the vascular plexus of the former first branchial arch
      artery may form the vascular component of an angiofibroma arising due to growth
      stimulation at the time of adolescents. CONCLUSIONS: Incomplete regression of the
      first branchial arch artery presenting an atavism is suited to explain the
      vascular tumour component of angiofibromas considering main tumour
      characteristics (origin in the posterior nasal cavity close to the sphenopalatine
      foramen, main blood supply from the maxillary artery with possible feeders
      arising from the internal carotid artery). Our embryological contributions
      support to define angiofibromas as vascular malformations.

PMID- 11973682
TI  - [First results of the wave-guide in CO2-laser surgical reduction of the
      hyperplastic nasal turbinates].
AB  - BACKGROUND: The CO2-laser-surgical reduction of the hyperplastic nasal turbinates
      represents a standard procedure in ENT-Surgery. In the presented paper, the
      authors introduce a new technique for the treatment of hyperplastic turbinates.
      METHODS: The laser beam is transmitted through a 90 degrees handpiece to the
      mobile "infra-guide" wave guide, which contains a 1 mm ceramic tube. By
      application of mirrow pieces with different angles, laser surgical reduction of
      those parts of the nasal turbinates is possible, which normally can not be
      reached by conventional, tangentially to the mucosa directed laser beams. The
      direction of the laser beam is controlled either optically, as in endonasal sinus
      surgery, or monitored through a camera. A total of 36 patients (22 women, 14 men,
      mean age 32.7 years) with nasal turbinate hyperplasia and either impaired nasal
      breathing and/or retronasal drip were treated with the new method. RESULTS: The
      laser wave guide represents a minimally invasive and basically complication-free
      method feasable on an outpatient basis. As a particular advantage, laser surgical
      reduction of the posterior parts of the inferior and also the middle turbinate is
      possible. The majority of the patients relates of an improvement of the
      preoperative symptoms (regarding reduction of impaired nasal breathing: 61.3 %,
      regarding reduction of post nasal drip 87.1 %). CONCLUSION: The laser wave-guide
      represents a basically complication-free, minimally invasive supplement to the
      different treatment modalities of the hyperplastic nasal turbinates.

PMID- 11973683
TI  - [Head and neck cancer surgery in the elderly].
AB  - BACKGROUND: The literature on management of advanced head and neck cancer in the
      elderly is limited. Diagnostic and treatment decisions may be implicated by
      advanced age itself. METHOD: Treatment outcomes of head and neck cancer in
      elderly patients were reviewed in the literature. The results should serve as a
      basis for an individualized treatment strategy. RESULTS: A comparison of data
      shows that chronologic age alone should not be a contraindication to adequate
      oncologic surgery. An aggressive approach to head and neck cancer management with
      curative intention can be also considered in high aged patients with advanced
      cancer. Surgical therapy of head and neck cancer can be as effective in elderly
      patients as in younger patients without a significant increase in mortality and
      complications. CONCLUSIONS: Head and neck cancer patients of all age groups
      should have a treatment of equal quality regardless of whether the expected
      outcome is cure or palliation.

PMID- 11973684
TI  - [Trauma of the Membranous Trachea Managed by the ENT-Surgeon].
AB  - BACKGROUND: Isolated perforations of the membranous trachea are extremely rare
      but potentially life-threatening complications of endotracheal intubations and
      minimally invasive tracheostomy techniques. Most of the case-reports have been
      written by thoracic surgeons or anesthesiologists but both the diagnostic
      procedures and the therapy are not standardized. The aim of this study was to
      evaluate the position of the ENT-surgery in the management of these lesions.
      PATIENTS AND METHODS: Over a period of 6 years we treated 5 females, 3 males and
      3 children with iatrogenic lacerations of the posterior tracheal wall. The
      lesions were complications of percutaneous tracheostomies or emergent
      intubations. The charts and videoprints of each patient were reviewed. RESULTS:
      Clinical presentation was marked in all patients by the characteristical symptoms
      of paratracheal air leakage, i.e. pneumothorax, emphysema or airway obstruction.
      In 6 patients the onset of the symptoms occurred with a significant delay until
      to 2 days after the lesion was originated. Perforations were located at the
      distal third (8) and at the medial third (2) of the trachea or the subglottic
      area (1) and had a vertical shape with a length of 0.3-5.5 cm. Surgical repair
      using a transtracheal cervical approach or an endoscopical procedure was
      performed in 8 cases. 3 lesions having a length below 2 cm were treated
      nonoperatively. Outcome was excellent in all patients but a certain percentage of
      them claimed cough and dysphonia one or more years after the acute phase.
      CONCLUSIONS: Because of their life-threatening character perforations of the
      membranous trachea must be diagnosed as soon as possible. However, the clinical
      presentation is not obvious in many cases. For the exact detection of the
      perforations rigid endoscopy is superior to flexible technique. The early
      surgical repair is recommended for the majority of the cases. Therefore, the
      transtracheal approach and endoscopical procedures are favorized. Moreover, these
      methods used routinely in ENT-surgery are also appropriate for lesions of the
      distal part of the membranous trachea and can be an alternative to the more
      invasive thoracotomy. Conservative treatment strategies should be limited to
      selected patients with small lacerations.

PMID- 11973685
TI  - [On the dependency of larynx carcinoma on steroid sex hormones].

PMID- 11973688
TI  - Industrial medicine and acute musculoskeletal rehabilitation. 1. Diagnosing and
      managing the injured worker with low back pain.
AB  - This self-directed learning module highlights the evaluation and management of
      the injured worker with low back pain (LBP). This chapter reviews the importance
      of recognizing the physiologic implications of a lifting injury and evaluating
      its structural etiology in a worker with LBP. A review of the steps required to
      make an accurate diagnosis is included. Justifying restrictions and prescribing
      therapeutic intervention is summarized. OVERALL ARTICLE OBJECTIVE: To be able to
      provide a step-by-step plan for evaluating, treating, and safely returning to
      work the injured worker with LBP.

PMID- 11973689
TI  - Industrial medicine and acute musculoskeletal rehabilitation. 2. Acute cervical
      spine and shoulder injuries in the industrial setting.
AB  - This self-directed learning module highlights the underlying anatomy and
      biomechanics of the cervical spine and shoulder as a basis for developing a
      differential diagnosis of contributing pathology in an industrial injury. This
      includes components of the history, examination, and appropriate diagnostic
      testing that are necessary to develop an optimal rehabilitation plan. Treatment
      options are reviewed and include medications, therapy, selective injections, and
      return-to-work programs in the industrial setting. OVERALL ARTICLE OBJECTIVES:
      (a) To be able to identify neck and shoulder pathology, (b) to effectively
      evaluate cervical spine and shoulder injuries, and (c) to rehabilitate acute
      cervical spine and shoulder injuries in the industrial setting.

PMID- 11973690
TI  - Industrial medicine and acute musculoskeletal rehabilitation. 3. Cumulative
      trauma disorders of the upper limb in computer users.
AB  - This self-directed learning module highlights various cumulative trauma disorders
      of the upper limb that may be seen in computer users. The biomechanics and
      ergonomics of computer users are addressed in relationship to specific neurologic
      and musculoskeletal conditions within the neck and upper limbs. In addition to a
      general overview of these conditions, a case presentation is used to show the
      evaluation and treatment of a computer user who has carpal tunnel syndrome and
      concomitant de Quervain tenosynovitis. OVERALL ARTICLE OBJECTIVES: (a) To review
      the important anatomic and ergonomic basis for upper limb cumulative trauma
      disorders in computer users and (b) to provide an example of evaluation and
      treatment.

PMID- 11973691
TI  - Industrial medicine and acute musculoskeletal rehabilitation. 4. Evaluation and
      management of the injured worker with a lower-extremity injury.
AB  - This self-directed learning module highlights the importance of recognizing the
      relationships between multiple, concurrent joint injuries in the lower extremity
      of an injured worker. This chapter focuses on evaluating the lower extremity and
      devising a rehabilitation program that incorporates the entire kinetic chain.
      Further recommendations for return to work are discussed. OVERALL ARTICLE
      OBJECTIVES: (a) To accurately recognize and diagnose coexisting injuries in the
      lower extremity and (b) to devise an evaluation and treatment program enabling
      the worker to return to work.

PMID- 11973692
TI  - Industrial medicine and acute musculoskeletal rehabilitation. 5. Effective
      medical management of industrial injuries: from causality to case closure.
AB  - This self-directed learning module highlights the physician's role in treating
      industrial injuries, from the initial causality determination to the eventual
      case closure. It is part of the chapter on industrial medicine and acute
      musculoskeletal rehabilitation in the Self-Directed Physiatric Education Program
      for practitioners and trainees in physical medicine and rehabilitation. The
      article reviews important factors in determining whether an injury is work
      related, particularly in the presence of preexisting, underlying conditions. The
      article addresses the roles of functional capacity examinations and work
      hardening programs in facilitating successful return to work. Interactions are
      outlined between work return and nonwork activities of daily living, as well as
      financial and psychologic barriers that may impede work return. Legal issues
      regarding independent medical examinations and depositions are reviewed. Guidance
      is offered for identifying those relatively few injured workers who may require
      referral for surgical or other consultations. OVERALL ARTICLE OBJECTIVES: (a) To
      review the important medical, administrative, and legal challenges involved in
      treating injured workers and to describe strategies that physiatrists use to
      overcome effectively these challenges.

PMID- 11973693
TI  - Industrial medicine and acute musculoskeletal rehabilitation. 6. Occupational
      health for special populations.
AB  - This self-directed learning module highlights work-related injuries in specific
      patient populations that the physiatrist may encounter. This chapter focuses on
      evaluating work-related injuries in the aging and disabled population. Specific
      problems encountered in pregnant working women and the dental profession are also
      summarized. Specific biologic and/or environmental factors as they relate to
      workers in the specific populations are reviewed. Strategies for evaluation,
      rehabilitation, and health care management of these workers are discussed.
      OVERALL ARTICLE OBJECTIVES: (a) To be aware of specific needs and environmental
      factors for disabled, aging, pregnant, and dental workers and (b) to identify
      what may precipitate injury for disabled, aging, pregnant, and dental workers.

PMID- 11973695
TI  - Focused review: myofascial pain.
AB  - Myofascial pain is defined as pain that originates from myofascial trigger points
      in skeletal muscle. It is prevalent in regional musculoskeletal pain syndromes,
      either alone or in combination with other pain generators. The appropriate
      evaluation and management of myofascial pain is an important part of
      musculoskeletal rehabilitation of regional axial and limb pain syndromes. This
      article reviews the current hypotheses regarding the pathophysiology of
      myofascial trigger points and muscle pain. A critical evidence-based review of
      the pharmacologic, nonpharmacologic, alternative medicine, and exercise
      treatments of myofascial pain is provided, as well as future research directions.
      OVERALL LEARNING OBJECTIVE: To review critically the state of the art knowledge
      of myofascial pain, including pathophysiology and comprehensive management. Areas
      of future research are identified.

PMID- 11973697
TI  - Spinal cord injury medicine. 1. Etiology, classification, and acute medical
      management.
AB  - This self-directed learning module highlights basic management and approaches to
      intervention-both established and experimental. The revised American Spinal
      Injury Association classification (2000) of spinal cord injury (SCI) further
      defines the examination and classification guidelines. The incidence of traumatic
      SCI remains at approximately 10,000 cases per year, with 32 years the average age
      at injury. Initial management includes establishment of oxygenation, circulation
      (mean blood pressure >85 mm Hg), radiographic evaluations for spine instability,
      intravenous methylprednisolone, and establishment of spinal alignment. Prevention
      measures for medical complications include pressure relief for skin,
      thromboembolism prophylaxis, prevention of gastric ulcers, Foley catheter
      drainage to prevent urine retention, and bowel care to prevent colonic impaction.
      Nontraumatic SCI from spinal stenosis, neoplastic compression, abscess, or
      multiple sclerosis becomes more common with aging. Experimental treatments for
      SCI include antibodies to block axonal growth inhibitors, gangliosides to augment
      neurite growth, 4-aminopyridine to enhance axonal conduction through demyelinated
      nerve fibers, and fetal tissue to fill voids in cystic spinal cord cavities.
      Early comprehensive rehabilitation at a SCI center prevents complications and
      enhances functional gains. OVERALL ARTICLE OBJECTIVE: To summarize the
      comprehensive evaluation and management of a newly injured individual.

PMID- 11973698
TI  - Spinal cord injury medicine. 2. Medical complications after spinal cord injury:
      Identification and management.
AB  - This is a self-directed learning module that reviews medical complications
      associated with spinal cord injury (SCI). It is part of a chapter on SCI medicine
      in the Self-Directed Physiatric Educational Program for practitioners and
      trainees in physical medicine and rehabilitation. This article includes
      discussion of common medical complications that impact rehabilitation and long
      term follow-up for individuals with SCI. Issues addressed include the
      rehabilitation approach to SCI individuals with pressure ulcers, unilateral lower
      extremity swelling (deep venous thrombosis, heterotopic ossification, fractures),
      along with the pathophysiology, assessment, and treatment of spasticity,
      autonomic dysreflexia, orthostatic hypotension, and pain. OVERALL ARTICLE
      OBJECTIVE: To describe diagnostic and treatment approaches for medical
      complications common to individuals with SCI.

PMID- 11973699
TI  - Spinal cord injury medicine. 3. Rehabilitation outcomes.
AB  - This self-directed learning module highlights rehabilitation outcomes in spinal
      cord injury (SCI). It is part of the chapter on SCI medicine in the Self-Directed
      Physiatric Education Program for practitioners and trainees in physical medicine
      and rehabilitation. This article focuses on the multiple concerns for functional
      recovery after SCI, chiefly, the potential for ambulation, upper-extremity
      recovery, options for functional neuromuscular stimulation (FNS), sexual
      activity, and optimal outcome after a metastatic lesion. Motor incomplete
      patients have a better prognosis for ambulation than persons with sensory
      incomplete injury. Positive predictors for ambulation, including pinprick and
      lower-extremity motor scores greater than 20, are discussed. Meaningful recovery
      can occur in the upper extremities for at least 1 year. FNS options have been
      developed to promote functional control of the upper extremities for persons with
      tetraplegia, phrenic pacing, and bladder continence. A critical component of an
      individual's expression of self is his/her sexuality; sexual function after SCI
      is described in detail, including options for treatment of erectile dysfunction
      and various birth control methods for women. Expectations for an appropriate
      rehabilitation stay for a person with metastatic SCI differ for an individual
      with traumatic SCI. Differences may include changing routine pathways and
      timelines to focus on patient-centered quality of life for transition to home.
      OVERALL ARTICLE OBJECTIVE: To identify potential outcomes in ambulation, upper
      extremity function, FNS, and sexual function after SCI and after metastatic
      cancer.

PMID- 11973700
TI  - Spinal cord injury medicine. 4. Optimal participation in life after spinal cord
      injury: physical, psychosocial, and economic reintegration into the environment.
AB  - This learner-directed module on spinal cord injury (SCI) presents a variety of
      perspectives of the process of personal and environmental adaptation for
      reintegration. Adaptation is unique to each person and does not predictably
      follow stages. Models used for understanding the process include biopsychosocial,
      ICIDH-2 (International Classification of Functioning, Disability and Health), and
      sector divisions of the environment. Home modification requires home
      (intermediate environment) evaluation and sociospatial behavioral mapping for
      planning and appropriation of remodeling in proportion to functional need and
      use. Options for access to the natural environment include specialized
      wheelchairs, climbing rigging, kayaks, and sail boats. Sports participation with
      adaptations is expanding and includes a larger variety of organizations and
      leagues. Economic needs are effectively anticipated with development of a life
      care plan. Procreative options to overcome infertility after SCI include
      vibratory stimulation for ejaculation, intravaginal insemination, intrauterine
      insemination, in vitro fertilization, and intracytoplasmic sperm injection.
      Approaches to requests for withdrawal of life-sustaining care include depression
      screening, pain evaluation, and assistance in accomplishment of person centered
      goals. Overall, community reintegration after SCI is continually improving
      because of better acceptance, accessibility, and technology for building
      adaptations. OVERALL ARTICLE OBJECTIVES: (a) To review models and theories of
      medical intervention and disablement and (b) to demonstrate their application in
      rehabilitation practice by designing unique treatment plans that meet patient
      person-centered goals.

PMID- 11973701
TI  - Spinal cord injury medicine. 5. Preserving wellness and independence of the aging
      patient with spinal cord injury: a primary care approach for the rehabilitation
      medicine specialist.
AB  - This self-directed learning module highlights consideration and treatment of
      individuals with long-term spinal cord injury (SCI). It is part of the chapter on
      SCI medicine in the Self-Directed Physiatric Education Program for practitioners
      and trainees in physical medicine and rehabilitation. This article specifically
      focuses on the challenges of chronic disease prevention, diagnosis, therapeutic
      options, and the resultant impact on the person with long-term SCI. With
      cardiovascular disease becoming a leading cause of mortality in this population,
      risk factor modification through weight, lipid, and glucose control becomes more
      important. Likewise, bowel dysfunction increases with duration and severity of
      SCI. Conservative and surgical management options are discussed. Musculoskeletal
      repetitive trauma injuries occur commonly in long-term SCI but can be prevented
      with appropriate lifestyle or equipment modifications. These and other conditions
      occurring in the person with long-term SCI are closely related to psychosocial
      function with resultant social isolation, depression, and substance abuse. Thus,
      identification and surveillance of these comorbidities are addressed, with an
      emphasis on prevention. OVERALL ARTICLE OBJECTIVE: To summarize the unique
      medical, psychosocial, and functional needs of the individual with long-term SCI.

PMID- 11973705
TI  - Pain management for the child with cancer in end-of-life care: APON position
      paper.
AB  - Although there have been major advances in the treatment of childhood cancer with
      an overall survival rate of more than 70%, cancer continues to be the leading
      cause of death in children resulting from disease. In 1998, 2,500 children in the
      United States died of cancer-related causes. Each year cancer kills more children
      than asthma, diabetes, cystic fibrosis, congenital anomalies, and acquired
      immunodeficiency syndrome combined. The Association of Pediatric Oncology Nurses
      (APON) is the leading professional organization for nurses caring for children
      and adolescents with cancer and their families. The highest standards of nursing
      practice are achieved through education, research, certification, advocacy, and
      affiliation. It is the position of APON that pain in the child dying of cancer
      can be effectively managed. This can be accomplished by making the prevention and
      alleviation of pain a primary goal, partnering with the patient and parents, and
      aggressively using appropriate pharmacologic and non-pharmacologic interventions.
      The pediatric oncology nurse has an essential role in the child's pain management
      at the end of life through nursing assessment, identifying expected outcomes, and
      performing and evaluating interventions.

PMID- 11973758
TI  - The physiology of continence: idiopathic fecal constipation and soiling.
AB  - The anatomic and functional elements contributing to fecal continence and
      defecation are explored. The high incidence and importance of chronic idiopathic
      constipation as an entity in itself and a contributing factor to fecal
      incontinence are emphasized, and its management is discussed. The importance of a
      proper clinical history and examination is highlighted, and investigative
      modalities including radiology, transit studies, and anorectal manometry are
      described and placed in the context of practical clinical management.

PMID- 11973759
TI  - Fecal incontinence in anorectal malformations, neuropathy, and miscellaneous
      conditions.
AB  - In the majority cases, fecal soiling in children is functional and usually
      associated with severe constipation. Fortunately, functional soiling is a self
      limiting problem and usually disappears at puberty. Organic fecal incontinence is
      a consequence of congenital malformations affecting the anorectum, anal
      sphincters, or the spinal cord. Inability to control bowel function may be
      permanent, as in patients with myelodysplasia; self-limiting, as in patients who
      have fecal soiling after a pull-through operation for Hirschsprung's disease; or
      partial, as in many patients who have undergone repair of an anorectal
      malformation. The purpose of this report is to review the etiology, long-term
      outcome, and evolution of the management of different types of organic fecal
      incontinence in children. Knowledge of the pathophysiology of fecal incontinence
      has accumulated during recent decades, and this provides the basis of modern
      treatment modalities that have revolutionized treatment so that today most
      patients can be provided total or at least social continence from early
      childhood.

PMID- 11973760
TI  - Recent innovations in the management of fecal incontinence.
AB  - The importance of having a reproducible scoring system to objectively assess the
      severity of fecal incontinence and its response to treatment is stressed, and a
      number of methods are described. The approach to conservative treatment and
      investigation is outlined. Recent advances in the surgical management of fecal
      incontinence including the electrically stimulated gracilis neosphincter, sacral
      nerve stimulation, the artificial anal sphincter, internal anal sphincter
      augmentation, rectal augmentation, and antegrade colonic irrigation are described
      in detail.

PMID- 11973761
TI  - Urinary incontinence and vesicourethral dysfunction in pediatric surgical
      conditions.
AB  - The most common cause for urinary incontinence in children with pediatric
      surgical conditions of the pelvic region and perineum is lower urinary tract
      dysfunction caused by concomitant sacral agenesis, especially in children with
      anorectal malformations. Another common cause is iatrogenic pelvic nerve damage
      secondary to reconstructive surgery. Moreover, an intrinsically altered pelvic
      floor anatomy as seen in some cases of complex cloacas, or disruption of pelvic
      floor muscles with consecutive loss of supportive structures, as in
      sacrococcygeal teratoma, should also be taken into consideration. It is important
      to understand that the causes of urinary incontinence in these children are not
      isolated problems concerning only the urinary tract. They may have the same
      negative impact on anorectal function as they have on the bladder and urethral
      sphincter. Therefore, children with pediatric surgical conditions of the pelvic
      and perineal region often will present with a combination of both fecal
      incontinence caused by anorectal dysfunction and urinary incontinence caused by
      vesicourethral dysfunction. The additional morbidity caused by urinary
      incontinence may have an enormous impact on the patient's life and well being,
      not only with regard to physical disability, but also in terms of emotional
      problems, social handicap, and socioeconomic burden. It is obvious that a
      patient's quality of life will be significantly reduced if he or she suffers from
      both fecal and urinary incontinence. Therefore, an integrated approach to the
      management of both vesicourethral and anorectal dysfunction should be developed
      to achieve the optimum care for these children.

PMID- 11973762
TI  - Enuresis and incontinence in children.
AB  - The terminology used to describe wetting children is defined. The etiologies of
      monosymptomatic nocturnal enuresis and nonneuropathic bladder-sphincter
      dysfunction are described. Treatment strategies and the results of recent large
      scale studies are presented.

PMID- 11973763
TI  - Assessment and conservative management of the neuropathic bladder.
AB  - The etiologies and forms of congenital neuropathic bladder are described:
      contractile (25%), acontractile (15%), and intermediate (60%). The terminology
      relating to neuropathic bladder is defined and the principles of bladder
      management are highlighted: (1) must achieve a bladder that can fill at low
      pressure, (2) must achieve a bladder that can store urine at low pressure, (3)
      must achieve sphincter resistance that is sufficient to allow urine storage, and
      (4) must put in place a mechanism of achieving complete voluntary bladder
      emptying. The approach to investigation is set out in a logical sequence, and the
      methods of achieving the goals highlighted above are described. All of this is
      put in the context of managing the handicapped patient as a whole. It also is
      stressed that the aim is not just to achieve continence but perhaps even more
      importantly to protect renal function.

PMID- 11973765
TI  - The management of urinary incontinence in the exstrophy complex, posterior
      urethral valves, and infrasphincteric ureters.
AB  - Urinary incontinence is a debilitating problem that requires careful evaluation.
      Causes of incontinence in children are numerous, and once the mechanism of
      incontinence has been identified, management can be planned carefully. The
      management and outcome in children born with the exstrophy-epispadias complex,
      posterior urethral valves, and children who have an infrasphincteric ureteric
      orifice are discussed in this article.

PMID- 11973764
TI  - Surgical management of the neuropathic bladder.
AB  - In a simplified view, the "normal" bladder, through a multifaceted neuromuscular
      event, allows the basic functions of urinary storage and emptying. More
      specifically, the urinary bladder accommodates increasing urinary volume with
      little to no increase in vesicular pressure while maintaining continence. The
      normal act of emptying integrates the relaxation of the urinary sphincters
      (external and internal) with the subsequent bladder contraction to void to
      completion when full. There are a multitude of conditions, both congenital and
      acquired, that can affect the bladder's ability to perform these functions in a
      smooth and coordinated fashion. The most common causes of pediatric bladder
      dysfunction necessitating surgical intervention are those associated with spina
      bifida/myelodysplasia, posterior urethral valves, and bladder exstrophy. Over the
      last 2 decades, the evolution of complex reconstruction for lower urinary tract
      dysfunction has resulted in an improved quality of life for children afflicted
      with upper urinary tract changes or incontinence despite maximum utilization of
      nonoperative therapies. Because each patient represents a unique therapeutic
      entity, an individualized approach to each child is recommended.

PMID- 11973767
TI  - [Abstracts of the annual meeting of the German Association for the Study of the
      Liver. January 25-26, 2002, Leipzig].

PMID- 11973766
TI  - Future trends in bladder reconstructive surgery.
AB  - The incorporation of bowel into the urinary tract is associated with significant
      long-term complications. Therefore, considerable efforts are being made to avoid
      the use of enteric epithelium in bladder reconstruction. The simplest of these
      entail the use of native urothelium that is already available, with techniques
      such as auto-augmentation, auto-augmentation de-epithelialized enterocystoplasty,
      and ureterocystoplasty. Unfortunately, in many patients, the bladder is too
      small, or dilated ureters are not available, and these techniques cannot be
      applied. Recently, experimental techniques are examining the use of tissue
      expansion to the ureter and bladder to increase the volume of tissue available.
      Tissue engineering techniques are being applied to bladder regeneration, and
      considerable advances have already been made leading to in vivo animal
      experimentation, the results of which are very encouraging. The details of these
      most recent advances will be discussed in detail in this report.

PMID- 11973768
TI  - Factors affecting end-stage disease quality of life. Physicians' prognostic
      predictions of life expectancy,.

PMID- 11973769
TI  - Specific spinal exercise substantially reduces the risk of low back pain
      recurrence.

PMID- 11973772
TI  - Peace and public health: 1999 Kosovo experience.

PMID- 11973771
TI  - Motor Relearning Program approach improves short-term motor outcomes and reduces
      hospital stay after stroke.

PMID- 11973774
TI  - Pediatric gastroenterology in South Africa: a personal perspective.

PMID- 11973775
TI  - A new formulation of ORS for children is warranted.

PMID- 11973776
TI  - Reduced osmolarity oral rehydration solutions: new and improved ORS.

PMID- 11973777
TI  - Genetic counseling in neonatal hemochromatosis.

PMID- 11973778
TI  - NICE work for nursing. Interview by Dina Leifer.

PMID- 11973781
TI  - To be or to do? That is the question.

PMID- 11973782
TI  - Dental research--not just for dentist anymore.

PMID- 11973784
TI  - A question of trust. Interview by Colin Parish.

PMID- 11973785
TI  - The butt stops here. Interview by Phil Coleman.

PMID- 11973786
TI  - Diabetes update.

PMID- 11973787
TI  - Net results.

PMID- 11973788
TI  - 2. Resuscitation: ward-based CPR.

PMID- 11973791
TI  - Informal carers count.

PMID- 11973792
TI  - Is there a place for epidemiology in nursing?
AB  - BACKGROUND: Epidemiological research is seen by many to have immense value in
      helping to determine the health of populations and in helping to plan and
      determine health service policy. Despite this it seems to be poorly understood
      and greatly underused by the nursing profession. CONCLUSION: Epidemiological
      studies can potentially offer considerable benefits to the way nurses incorporate
      health-related practices into their professional role. Research also offers a
      valuable opportunity for the nursing profession to become more active in helping
      to determine health policy issues. This article explores the nature of the
      dilemmas surrounding nursing and epidemiology and argues that nursing might be
      better served by a more proactive role in this valuable research discipline.

PMID- 11973794
TI  - Education issues surrounding the teaching of spirituality.
AB  - This article explores the emerging debate surrounding the teaching of
      spirituality in nurse education programmes. It is suggested that both historical
      and traditional approaches to nurse education can be complementary in preparing
      nurses to meet patients' spiritual needs.

PMID- 11973796
TI  - Credit where it's due.

PMID- 11973795
TI  - Tracheostomy care.
AB  - The author considers airway maintenance in the care of adult patients by
      providing a clinical overview of the pre- and post-operative requirements of
      tracheostomy care, including complications and the longer term implications that
      can arise immediately after tracheostomy surgery.

PMID- 11973798
TI  - A real eye opener.

PMID- 11973801
TI  - Re: Detourney, B. The value of economic modeling studies in the evaluation of
      treatment strategies for multiple sclerosis. (Editorial) Value Health 2002;5:1-2.

PMID- 11973802
TI  - Word from Washington.

PMID- 11973803
TI  - A state of blessed inspiration.

PMID- 11973804
TI  - [Prickling or pain of the skin related to PUVA therapy].

PMID- 11973805
TI  - [Food allergies and atopic dermatitis].

PMID- 11973806
TI  - Mental illness in the workplace after   Sutton v. United Air Lines.

PMID- 11973807
TI  - On the commodification of the black female body: the critical implications of the
      alienability of fetal tissue.
AB  - Recent scientific experimentation has revealed that fetal tissue yielded from
      abortions has remarkable therapeutic value. This Note posits that the demand for
      fetal tissue likely will expand to the point where the current supply no longer
      satisfies it. Therefore, in order to obtain tissue from women who would not
      otherwise donate their abortuses, should research organizations, pharmaceutical
      companies, and doctors be allowed to offer women a "financial incentive" for
      their fetal tissue? That is, should women be allowed to sell their fetal tissue?
      This Note explores the question from a Critical Race Theory perspective. It
      analyzes the impact that a market in fetal tissue will have on Black women, who
      are more likely to participate in such a market due to their precarious economic
      situation, their higher abortion rate, and the effects of internalized
      oppression. The Note concludes that because Black women will be
      disproportionately exploited, as well as disenfranchised from the benefits
      produced by a market in fetal tissue, fetal tissue should not be made market
      alienable.

PMID- 11973809
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 11973808
TI  - The assessment of DNA and RNA preservation in liquid based cytology media.

PMID- 11973810
TI  - National Hormone and Peptide Program.

PMID- 11973811
TI  - Sentinel-node technique will change the design of clinical trials in malignant
      melanoma.

PMID- 11973812
TI  - [The 75th annual meeting of the Japanese Society for Bacteriology. Yokohama,
      Japan. April 4-6, 2002. Abstracts].

PMID- 11973814
TI  - [The 46th Congress of the Japan Rheumatism Association. Kobe, Japan. April 22-24,
      2002. Abstracts].

PMID- 11973813
TI  - [The 102nd annual meeting of the Japan Surgical Society. Kyoto, Japan.  April 11
      13, 2001. Abstracts].

PMID- 11973815
TI  - [The 90th annual meeting of the Japanese Urological Association. Tokyo, Japan.
      April 17-20, 2002. Abstracts].

PMID- 11973816
TI  - [The 42nd annual meeting of the Japanese Respiratory Society. Sendai, Japan.
      April 4-6, 2002. Program and Abstracts].

PMID- 11973817
TI  - [77th annual meeting of the Japanese Society for Tuberculosis. Tokyo, Japan.
      April 16-17, 2002. Abstracts].

PMID- 11973819
TI  - Bibliography. Current world literature. Skin and soft tissue infections.

PMID- 11973818
TI  - Alcoholism and the ADA: divergent treatment by the federal courts.

PMID- 11973820
TI  - Bibliography. Current world literature. Respiratory infections.

PMID- 11973821
TI  - A three-dimensional method of visualizing the temporomandibular joint based on
      magnetic resonance imaging in a case of juvenile chronic arthritis.
AB  - AIM: The purpose of this study was to present a new visualizing method for
      temporomandibular joint (TMJ) pathology in 3D at several condylar positions and
      to apply the method to a case of juvenile chronic arthritis (JCA) with previously
      diagnosed bilateral TMJ disorder and to a subject without signs and symptoms from
      the TMJ. SUBJECT: The 20-year-old female patient had suffered from polyarticular
      JCA from the age of 6 years 8 months. The present study is based on a follow-up
      examination after the completion of orthodontic treatment with the Herbst
      appliance. Both TMJs were examined using magnetic resonance imaging (MRI) at
      closed and open mouth positions. The mandibular condyle, the glenoid fossa and
      the articular disc were segmented and 3D reconstruction of these structures was
      carried out. RESULTS: The condyle was characterized by an increased sagittal
      diameter with osteophyte-like formation at the anterior aspect of the condylar
      head and flattening of the superior surface. The depth of the glenoid fossa was
      reduced and the articular eminence was remarkably flat. The articular disc was
      markedly diminished and posteriorly placed on the condylar head. The distance of
      the condylar path during mouth opening was reduced and the curvature of the
      condylar path was quite flat. The disc moved slightly posteriorly on the condylar
      head and remained in the glenoid fossa during mouth opening. CONCLUSION: The
      imaging modality described improves visualization of TMJ morphology and gains
      insight into the TMJ pathology of the JCA patient, adding to understanding of the
      clinical problems.

PMID- 11973822
TI  - [The 58th annual meeting of the Japan Neurosurgical Society. Tokyo, Japan.
      October 27-29, 1999. Abstracts].

PMID- 11973823
TI  - The frequency of carpal tunnel syndrome in computer users at a medical facility.

PMID- 11973824
TI  - The frequency of carpal tunnel syndrome in computer users at a medical facility.

PMID- 11973825
TI  - The frequency of carpal tunnel syndrome in computer users at a medical facility.

PMID- 11973826
TI  - The frequency of carpal tunnel syndrome in computer users at a medical facility.

PMID- 11973827
TI  - Proposed diagnostic criteria for neurocysticercosis.

PMID- 11973828
TI  - Racism and medical science in South Africa's Cape Colony in the mid- to late
      nineteenth century.
AB  - Racism has been a particular focus of the history of Western medicine in colonial
      South Africa. Much of the research to date has paradoxically interpreted Western
      medicine as both a handmaiden of colonialism and as a racist gatekeeper to the
      benefits of Western medical science. This essay suggests that while these
      conclusions have some validity, the framework in which they have been devised is
      problematic. Not only is that framework contradictory in nature, it underplays
      differences within Western medicine, privileges the history of explicit and
      intentional racial discrimination in medicine, and encourages a separate analysis
      of racism in law, in the medical profession, and in medical theory and practice.
      Using the example of the Cape Colony in South Africa, this paper shows how
      legislation, class, institutional setting, and popular stereotypes could
      influence the form, timing, and degree of racism in the medical professional, and
      in medical theory and practice. It also argues for an analytical distinction
      between 'racist medicine' and 'medical racism.'

PMID- 11973829
TI  - The colonial world as mission and mandate: leprosy and empire, 1900-1940.
AB  - The history of medicine in twentieth-century empires has been dominated by
      studies of "imperial tropical medicine" (ITM) and its consequences. Historians
      have been fascinated by the work of medical scientists and doctors in the age of
      high imperialism, and there are many studies of medicine as a "tool of empire."
      This paper reviews work that explores colonial medicine as a broader enterprise
      than ITM in three spheres: missionary activity, modernization, and protection of
      the health and welfare of indigenous peoples. To illustrate the themes of mission
      and mandate, it discusses the development of policies to control leprosy in the
      tropical African and Asian colonies of Britain in the first half of this century,
      especially the work of the British Empire Leprosy Relief Association (BELRA).
      Although BELRA's efforts did little to change imperial medical and health
      agendas, they had an important impact locally and ideologically, and show how
      closely interwoven the themes of Christian caring, medical humanism, colonial
      development, and welfare policy had become by the outbreak of the Second World
      War.

PMID- 11973830
TI  - Bio-prospecting or bio-piracy: intellectual property rights and biodiversity in a
      colonial and postcolonial context.
AB  - Despite the rhetoric of decolonization following World War II, developing
      countries are, if anything, more dependent now on the science and technology of
      the developed world than they were in colonial times. This has led some critics
      to describe their situation as "neo-colonial." This paper will explore the issue
      in relation to the biotechnology industry, and to the 1993 United Nations
      Convention on Biodiversity. This convention challenged the assumption that the
      earth's biological and genetic resources are part of the "global commons" by
      giving property rights over these resources to the nation-states. While the
      objective of encouraging states to conserve biodiversity is universally endorsed,
      the strategy of using property law to do so is not. The search for new genetic
      and biological resources has become a major priority for the agrichemical and
      pharmaceutical industries, and despite continuation of the colonial tradition of
      appropriating indigenous knowledge and resources, new and more equitable models
      are being explored and developed within the convention's framework. These
      strategies, while controversial, offer the hope of a new and more just
      "International Genetic Order."

PMID- 11973831
TI  - Patient access to health care records.

PMID- 11973832
TI  - Human experimentation and the double facelessness of a merciless epoch.

PMID- 11973833
TI  - Technical revisions to medical criteria for determinations of disability. Final
      rules.
AB  - These final rules make a number of technical revisions to the Listing of
      Impairments (the listings). We use the listings when you claim benefits based on
      disability under titles II and XVI of the Social Security Act (the Act). We are
      making these revisions to reflect advances in medical knowledge, treatment and
      terminology, to clarify certain criteria in the listings, to remove listings that
      we rarely use, and to add new listings consistent with current medical practice.
      We are making these individual technical revisions in order to improve our
      medical listings and make them easier to understand and use.

PMID- 11973834
TI  - Qualitative research in thanatology.
AB  - A new research paradigm has been emerging which holds significant potential for
      the field of death studies. The qualitative project is a diverse collection of
      methodologies that focuses its interests on the words, narratives, and stories of
      individuals and groups. Part of its appeal may lie in the inherent closeness of
      fit between qualitative inquiry and applied work with the dying and the bereaved.
      The author introduces the individual articles in this special issue and outlines
      the development of the project as well as some current issues in qualitative
      research in thanatology.

PMID- 11973835
TI  - Shoestrings and bricolage: some notes on researching the impact of a child's
      death on family relationships.
AB  - An earlier version of this paper appeared as the appendix to our recent book, An
      Intimate Loneliness: Supporting Bereaved Parents and Children (G. Riches & P.
      Dawson, 2000). In it, we attempt to offer a brief history of the processes we
      have gone through in taking a simple research question, developing it into a
      practical proposal, experiencing how it shifted as we explored it, accounting for
      the changes that our broader reading imposed on our perceptions of what we were
      doing, and, finally, how the data itself and our efforts to understand it,
      resulted in a set of broad theoretical propositions rather than any tight
      conclusions.

PMID- 11973837
TI  - The making of a grounded theory: after death communication.
AB  - Qualitative research provides understanding of phenomena with a depth and
      richness that cannot be generated through quantitative approaches. Qualitative
      methods, however, can often appear difficult, if not confusing. In this article,
      the authors take the reader through the grounded theory process using Devers's
      research, Experiencing the Deceased: Reconciling the Extraordinary (1994), a
      study of after death communication (ADC), to illustrate the use of this
      particular qualitative method. The authors hope that this article will leave the
      reader with a better understanding of grounded theory method and stimulate an
      interest in using it for studying other death-related topics.

PMID- 11973838
TI  - Dying to know: qualitative research with terminally ill persons and their
      families.
AB  - This article illustrates the use of qualitative research methods in the field of
      thanatology. The authors--a former doctoral candidate and her dissertation chair-
      describe their ongoing naturalistic inquiry of terminally ill persons and their
      family members. By describing the reasoning and decision-making informing their
      study, the authors provide an instructive "how to" on the following topics:
      finding a research question and a method; assessing risks and benefits; sampling;
      gaining entry/access to research informants; participant observation;
      interviewing; analyzing data, and establishing "relational integrity." In a final
      section, the first author offers reflections on the personal challenges she faced
      while conducting her research.

PMID- 11973836
TI  - Taking a narrative approach to grief research: finding meaning in stories.
AB  - This article explores the concepts of narrative as story, of storytelling, and of
      the narrative approach to qualitative research. Within this, I will also examine
      the social nature of narrative and the implications of this for research. I will
      look at the process of conducting a narrative study and the implications for
      participation in such a project and for the researcher investigating a phenomenon
      through this frame. In particular, the need to create stories to make order of
      disorder and find meaning in the meaningless is particularly relevant to the
      study of grief. In looking at the process of conducting a narrative study,
      questions about what can be analyzed and how it might be presented, some
      strengths and limitations of the narrative approach, and ethical questions also
      are considered.

PMID- 11973839
TI  - The survival of micro-organisms in space. Further rocket and balloon-borne
      exposure experiments.
AB  - This report describes the results of survival studies of terrestrial micro
      organisms exposed directly to the space environment on two balloons and in two
      rocket flights. The work is part of a program to develop techniques for the
      collection of micro-organisms in the size range of micrometeorite particles in
      space or non-terrestrial atmospheres, and their return to earth in a viable state
      for further study. Previous survival studies were reported (J. Hotchin, P. Lorenz
      and C. Hemenway, Nature 206 (1965) 442) in which a few relatively large area
      samples of micro-organisms were exposed on millipore filter cemented to aluminum
      plates. In the present series of experiments, newly developed techniques have
      resulted in a 25-fold miniaturization resulting in a corresponding increase in
      the number of experiments performed. This has enabled a statistical evaluation of
      the results to be made. A total of 756 separate exposure units (each
      approximately 5 x 5 mm in size) were flown in four experiments, and organisms
      used were coliphage T1, penicillium roqueforti (THOM) mold spores, poliovirus
      type I (Pfizer attenuated Sabin vaccine strain), and bacillus subtilis spores.
      The organisms were deposited either by spraying directly upon the vinyl-coated
      metal units, or by droplet seeding into shallow depressions in the millipore
      filter membrane-coated units. Groups of units were prepared comprising fully
      exposed, inverted (screened by 2 mm of Al), and filter-protected organisms. All
      of these were included in the flight set, the back up set, and a laboratory
      control set. The altitude of the exposures varied from 35 km in the balloon
      experiments to 150 km in the rocket experiments. Times of exposures at altitude
      were approximately 6 hours for the balloon flights and about 3 minutes for the
      rocket experiments.

PMID- 11973840
TI  - The results of biological studies made on board the Voskhod and Voskhod 2
      spaceships.
AB  - The biological effects of flight and outer space factors were studied on
      biological specimens of various organization, viz. spiderwort microspores, dry
      seeds of the pine tree, wheat, onion and of other higher plants as well as on
      lysogenic bacteria and wine flies. Furthermore, lysogenic bacteria were studied
      for the effectiveness of a number of well known ray-proof substances (such as
      mercaptopropylamine, 5-methoxytriptamine, etc.). The specimens were secured in
      special containers both on board the spaceships and in the hip pockets of the
      astronaut Leonov's spacesuit. Biological effectiveness of the factors was
      evaluated by means of cytogenic, genetic and microbiological procedures. The
      analysis of the data obtained has shown that under the impact of the complex of
      flight and outer space factors, including ionizing radiation, both qualitative
      and quantitative changes occurred in the hereditary structures of some of the
      specimens, viz.: wheat seeds, spiderwort microspores and lysogenic bacteria.
      These changes were similar to the effects recorded in the flights of Vostok-2, 3,
      6. As compared to the controls, an enlargement was found in the cells of wheat
      sprout radicles, accompanied by chromosome rearrangements (N. L. Deloney et al.).
      Increased phage production by lysogenic bacteria (N. N. Zhukov-Verezhnikov, N. I.
      Rybakov et al.) and impairment of the mitosis mechanism in the spiderwort
      macrospores were demonstrated (N. L. Deloney, etc.). Higher frequency of dominant
      lethals and more frequent than normal chromosome indivergence in the wine flies
      were recorded. Quantitatively, the recorded drifts were insignificant (as was the
      case with the 'Vostok' spaceships' flights). Of interest are the results of the
      experiments on spiderwort microspores carried out with B. B. Yegorov's
      participation. The data obtained show that 1) during the mitosis stage spiderwort
      microspores show differing sensitivity to the space flight factors, and that 2)
      the mitosis stages support the previous hypothesis that impairment of the mitosis
      mechanism is due to the state of weightlessness, while chromosome rearrangements
      are chiefly induced by the effects of the complex of factors related to the take
      off and touch-down stages of the flight. (N. L. Deloney et al.). The analysis of
      beta-mercaptopropylamine and 5-methoxytriptamine tests indicates that these
      substances significantly reduce the phage producing activities of the lysogenic
      bacteria not only blocking the induced phage production but reducing the amount
      of spontaneous phage production as well (N. N. Zhukov-Verezhnikov, N. I. Rybakov
      et al.). Thus, the results of biological experiments on various specimens with
      differing degrees of radiosensitivity agree well among themselves and are
      consistent with the data on the dosage of space radiation.

PMID- 11973841
TI  - Circadian rhythms, space research and manned space flight.

PMID- 11973842
TI  - Individual differences in phase shifts of the human circadian system and
      performance deficit.
AB  - At periodic intervals throughout the biological day, assessments were made for a
      week prior to intercontinental flight yielding a reference of biological time set
      to the environment of origin, for two weeks at the temporally displaced
      environment of destination, and for a week following return to the environment of
      origin. Assessments made included rectal temperature, heart rate, respiratory
      rate, palmar evaporative water loss, urinalysis, reaction time, decision time,
      critical flicker fusion, subjective fatigue and well-being, and intellectual
      facility. The intercontinental flights consisted of east-west and west-east
      flights which permitted a comparative analysis of bidirectional effects of time
      zone displacements and a north-south flight which provided an appraisal of
      effects solely attributable to prolonged flight. Shifts of the phase of circadian
      periodicity manifested by the physiological functions were effected by the east
      west and west-east flights but not by the north-south flight. Bidirectional
      differences in lag time and extent of dissociation were revealed, but these may
      be due to individual variability. All flights engendered significant increment in
      subjective fatigue. Only one flight, the east-west, produced significant
      performance deficit indicating that while rapid translocation through many time
      zones does effect physiological phase shifts requiring 4-6 days for completion
      and impairment of well-being, these phenomena are not accompanied by a
      commensurate change in the efficiency of basic psychological functions.

PMID- 11973843
TI  - Daily rhythm changes associated with variations in light intensity and color.
AB  - Asynchronosis with its symptoms of fatigue, confusion, and discomfort is perhaps
      the most frequently experienced problem of jet travel; and without
      synchronization it will represent a major problem with supersonic and
      interplanetary travel. Current observations suggest that light is the most
      important environmental factor for the regulation of daily rhythms. Therefore,
      the purpose of this study was to quantitatively evaluate daily rhythm changes
      associated with changes in light intensity at given wavelengths of light.
      Biological rhythm data of birds have been useful for the interpretation of data
      collected on man. Two normal chickens were used to study three daily
      physiological rhythms in a controlled environment for approximately 80 days.
      Variables included the light intensity and wavelength. Heart rate, deep body
      temperature, and activity were recorded at 6 min intervals. The first two
      measurements were received from miniature radio transmitters and the third
      directly from the cage floor. The presence of the cycles was established by
      periodogram and correlogram analysis. The data were described further by harmonic
      regression analysis and cross correlations between the three daily rhythms. The
      physiologic systems studied are arrhythmic in continuous red light. There was no
      change observed in the periods of the daily rhythms with an increase in light
      intensity. Deep body temperature oscillations were greater at the higher light
      intensities and appeared to dissociate from heart rate. Activity and heart rate
      have a high degree of correlation even at the higher intensities.

PMID- 11973844
TI  - Human circadian rhythms in activity, body temperature and other functions.
AB  - From earlier studies in the field of 24-hr rhythms, it has been concluded that
      the rhythm is an exogenous one, governed by social influences on behavior and,
      perhaps, by cosmic stimuli. Recently, new steps have been made in two directions:
      1) the phase-relationships between many rhythmic functions have been described in
      detail; 2) it has been demonstrated that the rhythm is based on an endogenous,
      self-sustained oscillation. In conditions of isolation, subjects show a
      'circadian' rhythm whose frequency deviates from that of the earth's rotation. In
      case of such free-running rhythms, it may happen that different functions show
      different frequencies (internal desynchronization), suggesting that there exists
      a multiplicity of oscillators in the organism. The implications of these findings
      for problems in applied physiology are exemplified by the results of experiments
      in which organisms were exposed to shifts of the entraining light-dark cycle
      (simulating flights in eastward or westward direction). Re-entrainment lasts
      longer (and hence also the time of diminished efficiency) after a westward than
      after an eastward flight.

PMID- 11973845
TI  - Effect of reduced barometric pressure on water availability related to microbial
      growth.
AB  - Data obtained from Mariner IV indicate that the barometric pressure on Mars is
      considerably lower than previously estimated. Current estimates from Mariner IV
      indicate a range from 4 to 7 mb and by near infrared spectroscopy 33-56 mb.
      Inasmuch as the pressure has a marked influence on availability of water, this
      should affect the existence of Martian life. At the maximum temperatures recorded
      on Mars, namely 25 degrees C, a barometric pressure of 30 mb is required for the
      retention of free water. The lower pressure, 4 mb, would suggest that the
      moisture is present as a vapor above the freezing point and consequently it is
      not available for utilizing by living cells. The lower estimates of barometric
      pressure also inversely affect the carbon dioxide concentration in the Martian
      atmosphere. Our previous studies have demonstrated that spores of Bacillus cereus
      survive, germinate and grow in a simulated Martian environment (2.4% CO2, 98 mb)
      supplemented with moisture. The studies described in this paper were designed to
      determine the effect of low barometric pressures (10 to 98 mb Hg) and high
      concentrations of carbon dioxide (37 to 100%) in the simulated Martian
      environment on survival and growth of B cereus. The organism was inoculated into
      a felsite-limonite soil at 8% moisture level. The temperature cycles used were 8
      hr at -65 degrees C and 16 hr at 25 degrees C, or 20 hr at -65 degrees C and 4 hr
      at 25 degrees C. The data suggest that the organism after achieving maximum
      growth in the simulated Martian environment (2.4% CO2, 98 mb) immediately enters
      into the growth phase upon reinoculation into fresh soil. These data reflect upon
      the possibility of contamination through air movements. Based upon currently
      available Martian environmental data, the probability of contamination of Mars by
      terrestrial micro-organisms will be discussed.

PMID- 11973846
TI  - Ecological patterns of micro-organisms in desert soils.
AB  - The Atacama Desert's hardy aerobic microbial populations have been found to
      occupy ecological niches substantially different from those occupied by aerobic
      micro-organisms in the California and Valley of 10 000 Smokes deserts. Two
      specialized groups of microflora, the actinomycetes and micro-aerophiles, appear
      to be abundant in some portions of the Atacama Desert, though many of the
      bacterial and mold types and species common in the California deserts are absent.
      The factors defining the ecological niches and relationships of microbial
      populations in these soils are largely unknown. In several respects, moreover,
      micro-environments in these soils are similar to some of those expected on Mars.
      For the purpose of establishing the engineering constraints on the design of life
      detection instruments and their sampling and processing components, the nature
      and diversity of species of micro-organisms prevalent in the soils of extremely
      dry climates of the earth have not been adequately investigated. Useful
      ecological information about these soils will include an estimate of the likely
      lower limit in numbers or mass of viable aggregates in the autochthonous
      populations and the survivability of these populations under mechanical
      processing and isolated storage. Knowledge of the artificial niches, growth media
      for example, which members of these populations accept, will be useful in
      designing life detection instruments themselves. The range of practical designs
      for soil sampling devices will be determined by the nature of the particles and
      surfaces, and their depths, on which various physiological groups or largest
      populations of micro-organisms reside in the extremely dry deserts of the earth.
      The results of several exploratory experiments are used to provide some
      understanding of the environment and the ecological patterns of micro-organisms
      in soils of the earth's driest deserts.

PMID- 11973847
TI  - The influence of simulated low-gravity environments on growth, development and
      metabolism of plants.
AB  - Low-gravity environments may be simulated through appropriate horizontal
      clinostat rotation. This simulation is accomplished through a biological
      nullification of the directional component of gravitational force. Measuring
      biologically effective gravity force by organ response, it is readily
      demonstrated that biologically active gravitational force may be treated as a two
      dimensional vector. Though the magnitude dimension of this vector remains
      virtually constant anywhere on earth, the biologically effective direction
      dimension may be quantitatively altered by clinostat rotation, provided
      appropriate angular velocities and angles of inclination of clinostat axes are
      employed. Using oat seedlings, a rotation rate of 2 rpm, and a horizontal axis
      clinostat, a 'zero g' environment may be simulated. This simulated 'zero g'
      condition is attested by the inability of plants to perceive unidirectional
      gravitational force of sufficient magnitude to elicit directional growth. Under
      such conditions, plants will grow in the direction imparted by the initial
      orientation of the plants in the system. Geotropic curvature responses to
      subsequent geostimulation are, however, greater in seedlings grown under these
      conditions, nullifying the direction dimension of gravitational force, than in
      seedlings grown with rotation but with normal unidirectional gravity loads. Root
      growth under simulated 'zero' gravity conditions is likewise enhanced as compared
      to plants grown with rotation but normal unidirectional gravity. These
      differences in magnitude of growth and response to subsequent geostimulation are
      inexplicable on bases of modified auxin economy or production. Respiration rates
      are, however, materially enhanced by the simulated 'zero g' environments. This
      enhancement of respiration, as well as growth, quantitatively diminishes as the
      unidirectional gravity load is increased. These results imply that the primary
      effect of low-gravity environments is likely that of modifying the magnitude of
      respiratory metabolism. Such a modification is partly or wholly explicable on a
      basis of a modified distribution pattern of metabolically active particulate cell
      inclusions.

PMID- 11973849
TI  - Cardiovascular studies during and following simulation and weightlessness.
AB  - Two major characteristics of space flight may be simulated to some degree by bed
      rest and by water immersion. These are inactivity and the lack of the hydrostatic
      stress on the systematic circulation. Studies prior to the advent of space flight
      led to the prediction of orthostatic intolerance, muscular weakness, and calcium
      loss. Prolonged space flight has heightened the interest in these simulations to
      provide information concerning the temporal cause of the "deconditioning" or
      disuse syndrome and the value of simulation for testing the effectiveness of
      remedial measures. This report will evaluate the extent to which the simulation
      appears valid. In its gross effects, orthostatic intolerance can be studied with
      respect to its temporal course, etiology and effectiveness of remedial measures.
      The intolerance develops more rapidly during water immersion with respect to
      cause as well as effect. The short term of immersion studies does not allow study
      of the secondary change in blood volume due to red cell mass changes, Remedial
      measures seem clearly defined in water immersion simulation and less clear in bed
      rest. Measures of venous pooling following water immersion appear different than
      those obtained following weightlessness. There also appear to be differences in
      the results of evaluation of protective devices and measures and in the time
      course of development and recovery of orthostatic intolerance. Correlates of the
      cardiovascular responses such as muscle tone, skeletal strength, and endocrine
      change (catecholamines, vasopressin and aldosterone) suggest a marked alteration
      in physiology during hypodynamic status. To date, work on exposure to increased G
      force has provided only extrapolated data concerning metabolic requirements.

PMID- 11973848
TI  - Exobiology and the effect of physical factors on micro-organisms.
AB  - A study of the action of different physical factors on micro-organisms is
      necessary for a further development of exobiology. The action of temperature on
      crystalline preparations of catalase and peroxidase was studied by means of
      oscillographic polarography. A determination of the height of polarographic waves
      at the decrease of temperature from 20 degrees C to 0 degrees C has shown that
      structural elements of the peroxidase molecule connected with the enzymatic
      activity are more stable with the decrease of temperature cf. catalase. A
      relative resistance of the dehydrogenase activity in Az. vinelandii cells to high
      vacuum was found. Incubation of azotobacter cells under vacuum of 10(-9) mm Hg
      during 72 hr did not decrease the activity of alcohol and succinic dehydrogenase.
      Bac. cereus spores can be preserved from bactericidal UV action by thin films of
      chrome. The thickness of chrome film being 200-670 angstroms, spores are killed
      by a dose of 7.8 x 10(7) erg/cm2 at 253.7 microns wave length. Spores covered by
      chrome film thicker than 800 angstroms remain alive after this treatment.
      Investigations carried out with an 'Artificial Mars' camera led to the following
      results. The growth of Bac. megaterium on liquid growth media in this camera
      ceases as a result of UV rays killing all cells after 3 weeks. Untreated bacteria
      grow in the camera for a long time. Spore-forming bacteria isolated from the sand
      of the Kara-Kum Desert grow in ground limonite (with the addition of 2% garden
      soil) having maximum hygroscopic humidity (3.8%). Freezing and thawing (from -60
      degrees C to +25 degrees C) corresponding to day temperature deviations on Mars,
      low pressure (P=10 mm Hg) and the composition of the atmosphere (CO2-50%, N2-40%,
      Ar-10%) do not influence the growth of xerophylic bacteria under study. Humidity
      is the main factor limiting the growth of micro-organisms under 'Artificial Mars'
      conditions. According to the further development of the microbiological meteorite
      analysis methods, samples of rocks and stone meteorites were sterilized,
      incubated in the desert or on a snow surface in the Arctic and after different
      times (from 100 days to 7 months), investigated. In all cases, microbes were
      found only on the sample surfaces, whereas 1 cm from the surface and in the
      central parts micro-organism were completely absent. Hence, microbiological
      analysis of central parts of meteorites fallen in the Arctic or during dry
      periods of the year in the desert can give reliable results.

PMID- 11973850
TI  - [The share of the absence of gravity in the watchfulness process during manned
      space flights].

PMID- 11973851
TI  - Analysis of brain wave records from Gemini flight GT-7 by computations to be used
      in a thirty day primate flight.
AB  - It is planned to study central nervous, cardiovascular and metabolic functions in
      a 6.8 kg macaque monkey (Macaca nemestrina) flown in earth orbit for a period of
      30 days during 1967. Monitoring of central nervous functions will be by
      electroencephalographic (EEG) electrodes in surface and deep brain structures,
      and by electromyographic (EMG) recordings from neck and trunk musculature. Eye
      movements will be recorded by the electro-oculogram (EOG) and galvanic skin
      responses (GSR) will be assessed from the skin of the foot. Respiration will be
      recorded with an impedance pneumogram (ZPG), together with the electro-cardiogram
      (EKG). Behavioral tasks will involve tests of perception and recent memory
      (delayed matching to sample) and eye-hand coordination tests of vestibular
      functions and spatial orientation. Urine will be collected by a special
      catheterization technique and subjected to in-flight recording. Our extensive
      development of EEG spectral analysis techniques has proven the feasibility of
      accurate assessment of states of alertness, particularly in relation to decision
      making requirements, and states of drowsiness, fatigue and detection of levels of
      sleep, including dream states. We have applied these techniques to approximately
      60 hr of EEG data gathered on one subject in a Gemini astronaut flight (GT-7).
      Data will be presented on states of sleep and wakefulness in this subject during
      the first 55 hr of flight, with reference to possible changes induced by the
      space environment.

PMID- 11973852
TI  - Radiation measurements aboard the fourth Gemini flight.
AB  - Two special tissue-equivalent ionization chambers and 5 highly sensitive passive
      dosimetry packages were flown aboard the recent Gemini 4 flight for the purpose
      of obtaining precise values of instantaneous dose rate, accumulated dose. and
      shielding effectiveness. This experiment marked the first time that well-defined
      tissue dose and radiation survey measurements have been carried out in manned
      spaceflight operations. Since all measurements were accomplished under normal
      spacecraft environmental conditions, the biological dose resulted primarily from
      trapped inner Van Allen Belt radiation encountered by the spacecraft in the South
      Atlantic Anomaly. The experiment determined the particle type, ionizing and
      penetrating power, and variation with time and position within the Gemini
      spacecraft. Measured dose rates ranged from 100 mrad/hr for passes penetrating
      deeply into the South Atlantic Anomaly to less than 0.1 mrad/hr from lower
      latitude cosmic radiation. The accumulated tissue dose measured by the active
      ionization chambers, shielded by 0.4 gm/cm2 for the 4-day mission, was 82 mrad.
      Since the 5 passive dosimetry packages were each located in different positions
      within the spacecraft, the total mission surface dose measured by these detectors
      varied from 73 to 27 mrad, depending upon location and shielding. The particles
      within the spacecraft were recorded in nuclear emulsion, which established that
      over 90% of the tissue dose was attributable to penetrating protons. This
      experiment indicates that the radiation environment under shielded conditions at
      Gemini altitudes was not hazardous.

PMID- 11973853
TI  - Life sciences and space research V: a session of the Seventh International Space
      Science Symposium, Vienna, Austria, 10-18 May 1966.

PMID- 11973854
TI  - Naltrexone for alcohol dependence.

PMID- 11973855
TI  - Patent foramen ovale, atrial septal aneurysm, and recurrent stroke.

PMID- 11973856
TI  - Patent foramen ovale, atrial septal aneurysm, and recurrent stroke.

PMID- 11973857
TI  - Post-traumatic stress disorder and sleep.

PMID- 11973859
TI  - Mild asthma.

PMID- 11973858
TI  - Mild asthma.

PMID- 11973860
TI  - [The Sarqi medical school (11th-14th centuries): society and medicine in al
      Andalus Levante].
AB  - Most of the information about medical science in al-Andalus is associated with
      its leading figures and their work in the capital cities of the time: Cordoba,
      Seville, Granada, and the Taifal cities. This study presents the medicine of the
      Levantine or Sarqi al-Andalus region (10th-14th centuries). To this end, we have
      gathered reports on physicians that worked in the different Levantine capitals
      and have investigated key data in the biographical dictionaries, sources that
      have been little-used to study medical practice. We especially studied the
      Takmila by Ibn al-Abbar from Valencia.

PMID- 11973861
TI  - [The diseases yudam and baras (leprosy) in treatises of Islamic Law (Maliki
      Doctrine)].
AB  - Two diseases that appear in the legal treatises, yudam and baras, are
      semantically ambiguous and present difficulties when it comes to establishing
      their meaning. However, comparison of lexicographical and medical sources with
      modern bilingual and monolingual Arabic dictionaries bring us closer to the real
      meanings of the terms within the spacial and temporal contexts of the Maliki
      legal treatises. In these treatises, they appear as vitia redhibitoria in certain
      types of contract and also as diseases subject to regulations for the prevention
      of infection.

PMID- 11973862
TI  - [Hiding from the wolf, meeting the bear].

PMID- 11973864
TI  - [Synthesis of gonadotropins, their effects and the diseases linked to them].

PMID- 11973863
TI  - [From avoidance of proteins to amino acid transporter gene--a long journey of
      lysinuric protein intolerance].

PMID- 11973865
TI  - [Brain magnetic stimulation in neuropsychiatry].

PMID- 11973866
TI  - [Gestational diabetes mellitus].

PMID- 11973867
TI  - [Measuring the kidney function in drug trials and during drug therapy].

PMID- 11973868
TI  - [Susceptibility genes of familial breast cancer in Finland].

PMID- 11973869
TI  - [Hypermobility syndrome as a cause of joint symptoms].

PMID- 11973870
TI  - [Endovascular treatment of stenoses in cerebral, carotid and vertebral arteries].

PMID- 11973871
TI  - [Cervical dystonia].

PMID- 11973872
TI  - [Lip edema in a young ice hockey player].

PMID- 11973873
TI  - [Why change bronchitis terminology?].

PMID- 11973875
TI  - [A comment to Docent Pekka Nieminen].

PMID- 11973874
TI  - [Where does the term "nobelist" come from?].

PMID- 11973876
TI  - HIV case highlights costs of needlestick dangers.

PMID- 11973877
TI  - Investment trust.

PMID- 11973878
TI  - Whose lifestyle is it anyway?

PMID- 11973879
TI  - All lines are open.

PMID- 11973880
TI  - Inside story. Women's movement. Interview by Ian McMillan.

PMID- 11973881
TI  - A welcome return.

PMID- 11973882
TI  - The RCN Congress in Bournemouth.

PMID- 11973884
TI  - Defence mechanisms.

PMID- 11973883
TI  - Out in the cold.

PMID- 11973885
TI  - The great unwashed.

PMID- 11973891
TI  - Public health nursing: identifying priorities.

PMID- 11973892
TI  - The nurse's role in promoting breast awareness.
AB  - BACKGROUND: Breast cancer affects up to one in 12 women in the UK. Breast
      awareness, which is advocated in place of routine breast examination, involves
      women becoming more familiar with their bodies. CONCLUSION: Nurses have a vital
      role to play in encouraging women to become more breast aware. Their health
      promotion activities in this area can have an important impact on the uptake of
      breast screening initiatives.

PMID- 11973893
TI  - Student preparation in managing violence and aggression.
AB  - Nurses have suffered at the hands of violent patients and visitors for a long
      time, and incidents are on the increase. This article demonstrates the necessity
      of protecting nurses by training them to protect themselves when students.

PMID- 11973895
TI  - Leadership: improving the quality of patient care.
AB  - The satisfaction staff achieve from their work is in part determined by the style
      of management they work under. This article analyses the impact of a proactive
      leadership style on team performance and the quality of patient care.

PMID- 11973896
TI  - Immunisation.
AB  - Nurses' involvement in immunisation goes beyond simply giving vaccines. Jeannett
      Martin describes the nurse's overall role and responsibilities in administering
      these vital drugs.

PMID- 11973899
TI  - Pulse oximetry in practice.
AB  - Practice profiles are reflective pieces written by nurses in practice and based
      on continuing professional development articles. This week Nicola Neesam
      discusses injection sites.

PMID- 11973900
TI  - A whole new outlook.

PMID- 11973902
TI  - Changing tack on therapy.

PMID- 11973912
TI  - Competencies for hospital librarians.

PMID- 11973913
TI  - CHI services. When children are your primary clients.

PMID- 11973914
TI  - Accessing the Internet. Researching rare diseases and genetic disorders on the
      Internet.

PMID- 11973915
TI  - Product review. STAT!-Ref Medical Reference Library, Intranet version.

PMID- 11973916
TI  - Report from down under. Results of a benchmarking project.

PMID- 11973917
TI  - Inspector General criticizes handling of nursing facility mental health patients.

PMID- 11973918
TI  - Beware of citations for violation of activities regulations.

PMID- 11973919
TI  - [What kind of drug therapy should the society pay for?].

PMID- 11973920
TI  - [Rules of the game in drug marketing].

PMID- 11973921
TI  - [New drugs for the treatment of obesity].

PMID- 11973922
TI  - [Insulin analogs and new oral antidiabetic drugs].

PMID- 11973923
TI  - [Menopausal and post-menopausal hormonal replacement therapy in the prevention of
      cardiovascular diseases].

PMID- 11973924
TI  - [New opioid preparations in the treatment of pain].

PMID- 11973925
TI  - [New anti-inflammatory analgetics--are they needed?].

PMID- 11973926
TI  - [Older antidepressive agents].

PMID- 11973927
TI  - [Drug therapy of inflammatory bowel diseases].

PMID- 11973929
TI  - [New possibilities of the drug therapy of HIV infection].

PMID- 11973928
TI  - [Use of oral cephalosporins].

PMID- 11973930
TI  - [New antibacterial agents].

PMID- 11973931
TI  - [Central nervous system as a target for the new antihypertensive agents].

PMID- 11973932
TI  - [Drug concentration-effect correlation].

PMID- 11973933
TI  - It all adds up.

PMID- 11973935
TI  - Protecting the vulnerable public. Interview by Frances Pickersgill.

PMID- 11973934
TI  - Counting heads.

PMID- 11973936
TI  - Giving up the day job. Interview by Steven Black.

PMID- 11973937
TI  - An inspector calls.

PMID- 11973938
TI  - Go home!

PMID- 11973939
TI  - A change for the better.

PMID- 11973940
TI  - Did I ask for your opinion?

PMID- 11973941
TI  - Let's talk shop.

PMID- 11973942
TI  - Is presumed consent for organ donation better than our card-carrying system?

PMID- 11973948
TI  - World-wide health for all.

PMID- 11973949
TI  - Does reflexology impact on cancer patients' quality of life?
AB  - AIM: The objective of this study was to determine whether reflexology has an
      impact on the quality of life of patients in the palliative stage of cancer.
      METHOD: Twelve patients in the palliative stage of cancer with various tumour
      types were randomised into two groups. They were randomly assigned to receive
      either reflexology or placebo reflexology. All participants completed a linear
      analogue self-assessment scale relating to quality of life. All participants then
      received three sessions of either reflexology or placebo reflexology. The same
      person, a qualified reflexologist, provided the interventions for both groups.
      The participants were not aware of which intervention they were receiving. All
      participants then completed a second linear analogue self-assessment scale
      relating to quality of life. RESULTS: All participants felt that their quality of
      life had improved, even those who had received the placebo treatment. The
      reflexology group, however, reported more benefit than the placebo group. There
      was a significant difference (p = 0.004) between the reflexology group and the
      placebo group. CONCLUSION: This study showed that reflexology does have an impact
      on the quality of life of patients in the palliative stage of cancer.

PMID- 11973952
TI  - The rise and fall of cot sides.
AB  - Some researchers have questioned the use of cot sides, citing evidence that the
      incorrect use of them might be considered dangerous and even unethical. This
      article looks at some of the literature on the subject and discusses the results
      of an audit which was carried out in a large district general hospital last year.

PMID- 11973953
TI  - Preparation for advanced nursing roles.
AB  - Preparing nurses for working across traditional healthcare boundaries and to a
      higher level of practice requires a radical approach to post-registration
      education. Here, the authors propose a curriculum for primary health care that
      will equip nurses to meet the challenges of future healthcare provision.

PMID- 11973954
TI  - Nursing the patient with an external fixator.
AB  - External fixators are an effective way of fixing broken bones while at the same
      time optimising patients' mobility. In this article Julie Santy describes the
      major issues nurses need to be aware of to contribute effectively to patient
      care.

PMID- 11973956
TI  - The importance of mouth care.
AB  - Practice profiles are reflective pieces written by nurses in practice, and based
      on continuing professional development articles. This week Karen Bill discusses
      the importance of mouth care.

PMID- 11973959
TI  - Simpler than you think.

PMID- 11973960
TI  - Models for the community.

PMID- 11973965
TI  - [Chemotherapy improves the treatment results of cervical cancer].

PMID- 11973966
TI  - [Atrial fibrillation in a sportsman].

PMID- 11973967
TI  - [Evidence and medicine].

PMID- 11973968
TI  - [Smoking, increased serum protease activity and back problems].

PMID- 11973969
TI  - [Early interaction and the psychic development of a child].

PMID- 11973970
TI  - [LASIK method in correction of the refractive disorders of the eye].

PMID- 11973971
TI  - [How do radiologists describe the computer tomography findings].

PMID- 11973972
TI  - [A severe osteoporosis in a middle-aged man].

PMID- 11973973
TI  - [As a stranger in one's own home].

PMID- 11973975
TI  - [Maryland--Greece--Finland?].

PMID- 11973974
TI  - [Treatment guidelines for chronic obstructive pulmonary disease].

PMID- 11973976
TI  - [Treatment of drug dependence in Finland. November 1-3, 1999, Espoo, Finland].

PMID- 11973978
TI  - Early consultation. Interview by Colin Parish.

PMID- 11973977
TI  - Waiting game.

PMID- 11973979
TI  - Sound effects.

PMID- 11973980
TI  - Meet Northern Ireland's Nurse 2000. Interview by Julie McCaughan.

PMID- 11973981
TI  - The phone call that changed my life. Interview by Mary Hampshire.

PMID- 11973982
TI  - Handing on care.

PMID- 11973983
TI  - Sarnies down, there are tough choices ahead on care of older people.

PMID- 11973984
TI  - Court action.

PMID- 11973985
TI  - It's not natural.

PMID- 11973986
TI  - Mouth piece.

PMID- 11973991
TI  - Using diaries to identify CPD needs.

PMID- 11973992
TI  - Aggressive incidents on a psychiatric intensive care unit.
AB  - AIM: Although factors related to inpatient aggression have been extensively
      studied, there is relatively little specific information about violence in
      intensive care, so the authors decided to conduct their own research into the
      subject. METHOD: The authors studied the behaviours of the small number of
      patients who are involved in most of the aggressive incidents in a psychiatric
      intensive care unit (PICU) over 15 months. RESULTS: The study found that female
      patients were significantly more likely to be involved in aggressive incidents,
      but that most of these incidents involved self-harm. Patients with a diagnosis of
      schizophrenia were more likely to display violent behaviour than those from other
      diagnostic categories. Patients with a personality disorder were more likely to
      inflict violence against themselves. CONCLUSION: The authors concluded that all
      the research on patient violence needs to be standardised to inform practice
      properly. Nurses need to be aware that relatively few patients are responsible
      for most of the violent incidents that occur.

PMID- 11973993
TI  - Head injuries: acute care.
AB  - Nurses working in acute care settings will encounter patients with various head
      injuries. Philip Woodrow describes the nurse's role in care planning, monitoring
      and assessing these patients, and in providing a safe environment for their
      recovery.

PMID- 11973996
TI  - Piloting to a higher level.

PMID- 11973997
TI  - Making sense of higher level practice.

PMID- 11974000
TI  - Writing referral letters.

PMID- 11974005
TI  - Tsar potential. Interview by Ian McMillan.

PMID- 11974001
TI  - A new role in practice development.

PMID- 11974006
TI  - The shape of things to come.

PMID- 11974007
TI  - Mental health emergency.

PMID- 11974008
TI  - The write stuff.

PMID- 11974009
TI  - Time for a change.

PMID- 11974010
TI  - Fair's fair.

PMID- 11974011
TI  - You don't mean sex!

PMID- 11974012
TI  - Makeover or makeshift?

PMID- 11974013
TI  - . . . to the point.

PMID- 11974014
TI  - All to play for.

PMID- 11974018
TI  - Research ethics.

PMID- 11974019
TI  - Organisational culture and consultant nurse outcomes: Part 2. Nurse outcomes.
AB  - AIM: The aim of this three-year study was to investigate the development of a
      consultant nurse post and consider whether it contributed to a new organisational
      culture. METHODOLOGY: Action research was used because it focuses on developing
      practitioners, developing practice and contributing to understanding both the
      phenomena being studied and the processes being used. RESULTS: The role of
      leadership is recognised as key to bringing about cultural change, as is the use
      of approaches that clarify values and highlight the contradiction between
      espoused culture and culture in practice. CONCLUSION: This new culture had a
      positive impact on the unit in which it was based, on practitioners and their
      practice, and also on the trust. A number of factors, including transformational
      leadership, other facilitative processes, expertise in the practice of nursing,
      and other subroles of the consultant nurse were shown to be influential. Part
      one, published last week, described the concept of organisational culture. This
      article discusses the consultant nurse outcomes.

PMID- 11974020
TI  - Nursing intervention for pre-operative anxiety.
AB  - Surgical nursing is changing as the type of surgical procedures being performed
      are becoming more complex and the time for delivering nursing care is reducing.
      This has resulted in condensing the acute physical care required into a few
      hours, often to the detriment of other aspects of nursing intervention such as
      pre- and post-operative anxiety management. A pre-operative psychological care
      plan for use in a modern, dynamic, surgical arena is briefly outlined as no such
      strategy currently exists.

PMID- 11974021
TI  - BCG immunotherapy for carcinoma of the urinary bladder.
AB  - Treatment of superficial bladder cancer using BCG as an immunotherapeutic agent
      has proved effective. Stringent safety procedures have been introduced at Yeovil
      District Hospital so that this treatment is available to patients with bladder
      cancer, while ensuring that other patients and staff are protected from the
      possibility of BCG cross-infection.

PMID- 11974023
TI  - Promoting travel health for older people.
AB  - Older people are spending more time travelling for recreation than ever before.
      Irene Schofield considers what advice should be given to older clients to reduce
      any associated risks.

PMID- 11974026
TI  - Stricter HIV test protocols needed.

PMID- 11974030
TI  - Middle ground.

PMID- 11974031
TI  - And the winner is.... Interview by Charlotte Alderman.

PMID- 11974032
TI  - Improvements that money just can't buy. Interview by Charlotte Alderman.

PMID- 11974033
TI  - A dream product for advertisers. Interview by Charlotte Alderman.

PMID- 11974039
TI  - RCN branch pilot scheme.

PMID- 11974040
TI  - Clinical decision support tools in A&E nursing: a preliminary study.
AB  - AIM: This article describes how a large trust in the north east of England is in
      the process of developing a unique service for non-emergency patients in one of
      its main A&E departments. The Urgent Need Assessment Service (UNAS), co-located
      within the main A&E department, features the use of NHS Direct computerised
      algorithms to enable nurses to recommend the best treatment or course of action
      accurately and safely, for all patients attending the department who are
      categorised as blue or green status in accordance with the Manchester triage
      model of A&E assessment. The UNAS facility incorporates discretely staffed minor
      injuries and minor ailments services. METHOD: UNAS assessment nurses are
      specially trained to use their A&E experience, together with the computer model,
      and to make an assessment in partnership with the patient, sharing information
      displayed on the computer screen and working together to reach a jointly agreed
      treatment plan or outcome. The UNAS pilot and evaluation commenced in September
      1999 and results and outcomes are presented for the period from September 3 to
      December 31 2000. RESULTS: Approximately 75 per cent of all A&E attenders are
      given blue or green status. UNAS has led to faster treatment and reduced waiting
      times for these people, increasing patient satisfaction while enabling the A&E
      department to concentrate its resources on treating more serious cases.
      CONCLUSION: This pilot study has proved to be highly satisfactory to the majority
      of people who have been treated at UNAS. Those previously regarded as
      'inappropriate attenders' might be better suited to treatment in a different
      department, separate from the traditional A&E department, with reduced waiting
      times, and under the care of specially trained nurses.

PMID- 11974043
TI  - A post-modern nursing model.
AB  - For some time, nursing has been based on the structure of the nursing process and
      nursing models. However, in an age where the old order of science and medicine
      can no longer answer all of society's questions, can a nursing model, with its
      roots firmly based in the modernist structure of the nursing process, be post
      modern?

PMID- 11974044
TI  - Problems faced by homeless men in obtaining health care.
AB  - The vast majority of homeless people in the UK are male. In addition to becoming
      susceptible to many illnesses and to alcohol abuse, homeless men face a number of
      problems in accessing health care. A transformation of the health services is
      required to meet the needs of this vulnerable group.

PMID- 11974045
TI  - Blood transfusion.
AB  - Blood transfusion is a potentially dangerous treatment in which adverse reactions
      are rare but can be fatal. This article introduces recently published national
      guidelines for the care of recipients of a blood transfusion (BCSH 1999) and
      focuses in particular on the responsibilities of nurses and midwives.

PMID- 11974047
TI  - Treating lung cancer.
AB  - Practice profiles are reflective pieces written by nurses in practice and based
      on continuing professional development articles. This week Ruth Garner discusses
      the role of the lung cancer nurse.

PMID- 11974049
TI  - The trouble with men....

PMID- 11974050
TI  - Fairness to the fore.

PMID- 11974056
TI  - [Foreword to the Advent speech].

PMID- 11974057
TI  - [Advent speech].

PMID- 11974058
TI  - [Humanity in the mirror of nanotechnology].

PMID- 11974059
TI  - [The God on the screen?].

PMID- 11974060
TI  - [The fourth revolution].

PMID- 11974061
TI  - [Know yourself!].

PMID- 11974062
TI  - [Virtuality as man's new dimension].

PMID- 11974063
TI  - [Slave trade--humans as the media of exchange].

PMID- 11974064
TI  - [The ethics of genes].

PMID- 11974065
TI  - [Psychobiology of fidelity].

PMID- 11974066
TI  - [The second self of Lars Levi Leastadius].

PMID- 11974067
TI  - [G.A. Wallin--a healer and an explorer].

PMID- 11974069
TI  - [Are dog owners healthier than others?].

PMID- 11974068
TI  - [On oenodotes and oenotherapy--wine in medicine].

PMID- 11974070
TI  - [Superstition in the health care--legs or head first?].

PMID- 11974071
TI  - [Choosing the side in a double bed: acquired, inherited or sex-related trait?].

PMID- 11974072
TI  - [Does chocolate relieve Christmas season stress?].

PMID- 11974073
TI  - [Catching the Christmas fish].

PMID- 11974074
TI  - [Which fly does the fish like best?].

PMID- 11974075
TI  - [Wholesome Christmas fish].

PMID- 11974076
TI  - [Radical neck dissection].

PMID- 11974077
TI  - [An odd ECG].

PMID- 11974078
TI  - [A mysterious question mark on the back].

PMID- 11974079
TI  - [The Sauna elf--the keeper of the Sauna].

PMID- 11974080
TI  - Shackled to the NHS.

PMID- 11974081
TI  - DAZLing success.

PMID- 11974082
TI  - Hitting the perfect beat.

PMID- 11974083
TI  - On the party circuit.

PMID- 11974084
TI  - Sick and tired. Why do nurses have higher sickness rates than other
      professionals?

PMID- 11974088
TI  - Health care and Europe.

PMID- 11974089
TI  - Obstacles to defining the role of the mental health nurse.
AB  - BACKGROUND: This article review 0s the available literature to find a definition
      of the primary function of the mental health nurse. CONCLUSION: A number of
      obstacles were encountered that would need to be tackled to achieve a consistency
      of thought across the profession.

PMID- 11974090
TI  - Diverticular disease.
AB  - Diverticular disease is a gastrointestinal disorder. Christine Hyde discusses the
      physiology and care of related conditions in the large bowel, examining potential
      surgical outcomes.

PMID- 11974091
TI  - Occupational health for all.

PMID- 11974092
TI  - Way to go.

PMID- 11974093
TI  - Learning partners.

PMID- 11974097
TI  - On the same team.

PMID- 11974094
TI  - Top of the class.

PMID- 11974098
TI  - Giving the right signals.

PMID- 11974099
TI  - Counting on quality.

PMID- 11974100
TI  - Period piece.

PMID- 11974102
TI  - Register revamp.

PMID- 11974101
TI  - Unfulfilled potential.

PMID- 11974103
TI  - Only a last resort.

PMID- 11974104
TI  - Sadly missed?

PMID- 11974105
TI  - Life as a wage slave. We asked our readers panel whether student nurses should be
      paid a wage instead of a bursary.

PMID- 11974107
TI  - Triple integration nursing.

PMID- 11974108
TI  - Clinical facilitators: a new way of working.
AB  - AIM: To improve the quality and quantity of student clinical placements in an NHS
      trust. METHOD: When nurse training was under review, a 12-month pilot study was
      undertaken to introduce 12 clinical facilitators to acute and surgical wards at
      six trust sites on a supernumerary basis. As well as guiding the student, each
      facilitator liaised with a link tutor and ward staff, thereby maintaining
      continuity. The project team worked closely with the trust audit department and
      collected data using a variety of methods. The project leader developed an audit
      questionnaire for students, ward staff and college tutors. The initial answers
      were used as a baseline, then the same questionnaire was redistributed so the
      data could be analysed and compared. RESULTS: Most of the students felt more
      supported and confident to practise. The clinical facilitators were able to help
      ground the tutors' practice knowledge in reality, and the tutors built up the
      clinical facilitators' confidence in curricular issues and skills, such as
      presentation and teaching strategies. CONCLUSION: The clinical facilitator can
      strengthen partnerships between education and service and offer a model for
      practical facilitation.

PMID- 11974109
TI  - Anticipating the decline of the large general hospital.
AB  - Changing attitudes to healthcare provision look set to prompt a move away from
      treating patients in large general hospitals. Hospitals would then be left to
      deal with acute problems, while local provision would cater for patients
      requiring care.

PMID- 11974110
TI  - Evidence-based practice in neurology: a team approach to development.
AB  - Healthcare practitioners aspire to evidence-based practice, but in reality, many
      find it difficult to integrate the findings and recommendations of research
      studies and practice development projects into practice. One potential solution
      is a team approach to evaluating the available evidence and adapting it for use
      in a particular setting. Success depends on maintaining a team approach and
      ensuring that all staff members have access to the relevant information collated
      on the particular area of practice.

PMID- 11974111
TI  - Cystic fibrosis: adolescent care.
AB  - On reaching adolescence, children with cystic fibrosis develop different needs
      and become more independent, which means taking more responsibility for their own
      care. This article discusses the changing needs of adolescents with cystic
      fibrosis.

PMID- 11974113
TI  - Factors of life.

PMID- 11974117
TI  - The man with the plan. Interview by Christian Duffin.

PMID- 11974119
TI  - Make the grade.

PMID- 11974120
TI  - Sweet smell of success.

PMID- 11974121
TI  - Research matters.

PMID- 11974122
TI  - Rethink the weighting game.

PMID- 11974124
TI  - Turning over a new leaf.

PMID- 11974123
TI  - Finger on the pulse.

PMID- 11974125
TI  - 3. Nutrition and hydration: feeding adults.

PMID- 11974131
TI  - Human rights.
AB  - An examination of the impact of the Human Rights Act on health care.

PMID- 11974132
TI  - The use of directly observed therapy in TB: a brief pan-London survey.
AB  - AIM: The objective of this study was to investigate issues regarding adherence
      with tuberculosis therapy and the use of directly observed therapy. METHOD: A
      small-scale survey of TB nurse specialists at chest clinics in London was carried
      out to determine the current use of directly observed therapy for patients with
      tuberculosis in London. RESULTS: Responses to this survey indicate that directly
      observed therapy is currently used in less than half the available services in
      London. Many of the specialist TB nurses indicated that lack of resources and
      time were drawbacks to implementing directly observed therapy. CONCLUSION:
      Directly observed therapy was found to be a strategy that was infrequently used
      as a last measure for those people who were previous non-adherers.

PMID- 11974134
TI  - Keeping the person in the centre of nursing.
AB  - This article presents an overview of what it means to be a person and how this is
      articulated in person-centred approaches to practice. Nursing assessment is used
      as an example of a person-centred approach to care.

PMID- 11974135
TI  - Understanding lupus.
AB  - Lupus is a chronic inflammatory disease mainly affecting women of childbearing
      years. Angela Barwick discusses the condition, dealing with the diagnosis itself,
      the symptoms, treatment and the effects on the patient's lifestyle and wellbeing.

PMID- 11974137
TI  - Tailored service.

PMID- 11974143
TI  - Bone of contention.

PMID- 11974144
TI  - Old PALS act.

PMID- 11974145
TI  - NHS Plan. Stand by me. Interview by Charlotte Alderman.

PMID- 11974146
TI  - Why patients sue.

PMID- 11974147
TI  - Soothing the way. Interview by Catherine Sadler.

PMID- 11974148
TI  - Right thinking.

PMID- 11974149
TI  - Healing healers.

PMID- 11974150
TI  - Factor analysis.

PMID- 11974151
TI  - Ten easy ways to manage a project.

PMID- 11974155
TI  - NHS direct Wales: a national nurse-led service.

PMID- 11974156
TI  - Nurse prescribers: infrastructures required to support their role.
AB  - AIM: This study aims to answer the question: what are the opinions of nurse
      prescribing students about infrastructures required to support nurse prescribing?
      METHOD: Two researchers collected data from 12 focus groups (six health visitor
      and six district nurse groups) made up of students undertaking a course in nurse
      prescribing at the University of Central Lancashire. The total number of people
      who participated in the study was 146. RESULTS: Ten themes were identified by the
      focus groups as necessary infrastructures to support nurse prescribing.
      CONCLUSION: The results indicate that, for nurse prescribers to fulfil their new
      role effectively, a variety of mechanisms are necessary. These supporting
      infrastructures are vital to the success of nurse prescribing and are likely to
      result in a more confident and competent prescribing workforce.

PMID- 11974157
TI  - Integrated nursing teams in primary care.
AB  - BACKGROUND: This article looks at different models of integrated nursing and more
      traditional models of community nursing in primary care, as well as examining
      models of change for implementing integrated nursing. CONCLUSION: The models of
      change used by those who have developed integrated nursing teams successfully
      will be useful for anyone embarking on a similar project.

PMID- 11974158
TI  - The biological and nursing implications of pancreatitis.
AB  - Joseph McArdle examines the physiology of pancreatitis, discussing the nurse's
      contribution to the patient's recovery. He addresses the need for blood glucose
      monitoring during an acute episode, contrasts the risks associated with
      venepuncture and capillary sampling and identifies good practice in capillary
      blood glucose sampling.

PMID- 11974165
TI  - First port of call.

PMID- 11974164
TI  - American magnetism.

PMID- 11974166
TI  - The future of nursing.

PMID- 11974167
TI  - Laying it on the line.

PMID- 11974169
TI  - Leading the way. Interview by Colin Parish.

PMID- 11974168
TI  - The quiet revolution.

PMID- 11974170
TI  - Putting you wise.

PMID- 11974171
TI  - All bunged up.

PMID- 11974173
TI  - Mind over matter.

PMID- 11974175
TI  - Pressure ulcer guidelines.

PMID- 11974177
TI  - Fever management in children.
AB  - Treating a child with a fever is a skilled nursing activity. This article
      explains the underlying physiological mechanisms of a fever and relates these to
      the clinical signs, symptoms and care of children.

PMID- 11974176
TI  - Problem drinkers among acute care inpatients.
AB  - AIM: The objective of this study was to determine the prevalence of potential
      problem drinking among general hospital inpatients during a three-month period.
      METHOD: The study was conducted in a large Scottish teaching hospital. The wards
      involved were the general medical, general surgical, orthopaedic and short-stay
      wards as they had been identified as clinical areas with problem drinking among
      inpatients. Patients were interviewed using a structured interview schedule as a
      screening instrument to detect potential problem drinkers. RESULTS: Of the
      patients interviewed, 25 per cent were shown to drink in excess of the BMA's
      guidelines for low-risk drinking: 8 per cent had had previous treatment for
      alcohol problems; 2 per cent were bout or seasonal drinkers; and 15 per cent were
      newly identified potential problem drinkers. Of the newly identified group, 75
      per cent were men and 25 per cent women. Those who were unemployed formed the
      largest group of potential problem drinkers according to occupation, and patients
      from the short-stay ward were more likely to have an alcohol problem than those
      from other wards in the study. CONCLUSION: The patients in this study found to be
      at risk of experiencing alcohol-related problems might not be routinely
      identified with current screening methods. This method of screening, by asking
      patients about their recent drinking patterns, will help nurses to identify those
      who are potential problem drinkers and enable them to provide relevant advice and
      education to these patients.

PMID- 11974180
TI  - Venous leg ulcers: the role of the GP and district nurse.
AB  - AIM: To identify the healing rates for patients with venous leg ulcers (VLUs) who
      are nursed by district nurses. METHOD: The researchers performed a retrospective
      chart review of patients treated for VLU disease by district nurses to determine
      the healing rate, time to heal and variables associated with diagnosis. Forty
      random charts were abstracted from seven surgeries in Oxfordshire. RESULTS: Forty
      per cent of patients healed in less than 12 weeks and a further 42.5 per cent
      healed in 6.5 months. Some trusts and GPs lack understanding of what the district
      nursing service can offer patients with VLUs. CONCLUSION: If district nurses work
      collaboratively with GPs, either in the home or in a weekly clinic, they can
      provide good care to patients with VLUs.

PMID- 11974182
TI  - The management of a patient with lymphoedema of the legs.
AB  - Lymphoedema is a much under-publicised condition, yet it affects many people.
      Janice Bianchi and Marie Todd outline the implications of the condition and
      examine the treatment options of a typical case study.

PMID- 11974183
TI  - Three steps to effective wound care.
AB  - Optimal care of leg ulcers and pressure sores does not depend simply on the
      choice of dressing. The cause of the wound must be investigated, and other
      systemic factors related to wound healing must be assessed, then the wound
      environment can be evaluated and the most suitable dressing applied. Georgina
      Casey looks at these three steps to good wound care.

PMID- 11974185
TI  - Undertaking leg ulcer research in primary care.
AB  - Evidence-based practice has become a by-word in leg ulcer care, but the picture
      is far from complete. More research is needed. Carrying out the research to
      ensure quality care in a primary care setting brings practical difficulties and
      raises issues which must be resolved, as a research team from Birmingham
      University shows.

PMID- 11974184
TI  - Wound care on the Internet.
AB  - With public attention firmly focused on 'web' topics, Michael Clark considers the
      current position and future direction of wound care in his guide to the Internet.

PMID- 11974188
TI  - Pain and tissue trauma during dressing change.
AB  - BACKGROUND: Preventing patient pain and tissue trauma to the wound and
      surrounding skin are key considerations for nurses at the time of dressing
      changes. Mark Collier and Helen Hollinworth present the preliminary findings from
      a recent survey among nurses with an interest in wound care on the selection of
      dressing types. CONCLUSION: Education of student and post-registration nurses
      about the properties of dressing products, with an understanding of the potential
      detrimental effects as a result of pain and trauma, is needed to help promote
      quality wound care. Selecting appropriate dressings was reported as the main
      strategy nurses adopted to help prevent pain and trauma at the time of dressing
      change. Appropriate product selection can improve patients' quality of life and
      optimise wound healing potential.

PMID- 11974189
TI  - Lessons from the fast lane. Interview by Frances Pickersgill.

PMID- 11974193
TI  - The young at heart.

PMID- 11974195
TI  - Moving up the ladder.

PMID- 11974197
TI  - Meals on wheels.

PMID- 11974196
TI  - Notice to quit.

PMID- 11974198
TI  - The alternative therapy.

PMID- 11974199
TI  - Stakeholder thinking. Interview by Frances Pickersgill.

PMID- 11974200
TI  - Don't be hasty.

PMID- 11974201
TI  - How to be a model leader.

PMID- 11974203
TI  - Health, illness and culture.

PMID- 11974205
TI  - Referral criteria.
AB  - Criteria for referral to the district nursing service need to be drawn up in
      response to the Audit Commission Report (1999), with the aim of reducing the
      number of inappropriate referrals and providing patients with a more efficient
      service.

PMID- 11974204
TI  - Research revealed.
AB  - AIM: The objective of this study was to investigate nursing research, including
      topics, funding and publication. METHOD: A database of published biomedical
      research set up by the Wellcome Trust was analysed for nursing research. RESULTS:
      Topics covered in nursing research were found to be diverse, with mental health
      nursing and nurse education the major areas. Multi-authorship is lower than in
      biomedical research generally. The most prolific areas of publication are London
      SE postcodes and Manchester. Only about a third of nursing research appears to be
      funded. CONCLUSION: Nursing research was found to be the fastest growing field of
      biomedical research during the period analysed (1988-1995).

PMID- 11974207
TI  - Psoriasis.
AB  - Patients with psoriasis can find the psychological impact of the disease as
      debilitating as the physical symptoms. Helen Cloote describes the different types
      of psoriasis and the treatment methods available and emphasises the important
      role of the nurse in helping patients to come to terms with this condition.

PMID- 11974211
TI  - In the balance.

PMID- 11974206
TI  - Minority integration in rural healthcare provision: an example of good practice.
AB  - To ensure that ethnic minority groups were receiving equality of treatment and
      service, Horton General Hospital in Banbury formed a multicultural consultation
      group. The group carried out a five-year plan to standardise health care for
      ethnic minority communities in Oxfordshire and to educate staff to enhance their
      cultural sensitivity.

PMID- 11974212
TI  - Too young to be a mum.

PMID- 11974213
TI  - It's what your feet are for.

PMID- 11974214
TI  - Making waves. Interview by Alison Moore.

PMID- 11974215
TI  - Don't leave.

PMID- 11974216
TI  - Lifelong ambitions.

PMID- 11974217
TI  - Beating pain.

PMID- 11974218
TI  - Immediate access. The clinical nurse needs the Internet just as much as any
      academic.

PMID- 11974221
TI  - Socio-economic welfare of nurses: a statement from the International Council of
      Nurses.
AB  - This report outlines a position statement by the International Council of Nurses
      (ICN), advocating equality, a fair and comparable wage and appropriate workplace
      environments for nurses.

PMID- 11974222
TI  - The use of portfolios in the assessment of learning and competence.
AB  - BACKGROUND: Portfolios have been used to incorporate accreditation of prior
      learning into nursing and midwifery assessment. This article aims to review the
      available literature on the use of portfolios. CONCLUSION: There needs to be a
      thorough evaluation of portfolios to determine their effectiveness as assessment
      tools in relation to the curriculum.

PMID- 11974223
TI  - Vaccine administration.
AB  - There has been a big increase in the number of vaccinations administered by
      nurses in the past few decades and it is now a regular part of many nurses'
      workloads. This article looks at the process of immunisation, focusing on the
      injection site, choice of equipment and technique.

PMID- 11974227
TI  - More than a survey.

PMID- 11974224
TI  - Central venous access devices.
AB  - Central venous access devices are used in hospital and in the long term for
      patients who receive therapy in the community. This article explores the history
      and development of these devices as well as the nurses role in their insertion
      and care.

PMID- 11974228
TI  - Family fortunes.

PMID- 11974229
TI  - Hope is in the hands of nurses.

PMID- 11974230
TI  - I can see clearly now. Interview by Debbie Smith.

PMID- 11974232
TI  - Make my day.... What single thing could management do to improve the quality of
      your nursing?

PMID- 11974231
TI  - No need to starve.

PMID- 11974233
TI  - Joint decisions.

PMID- 11974234
TI  - A course of action.

PMID- 11974235
TI  - Fluid mechanics.

PMID- 11974237
TI  - Clinical Standards Advisory Group: services for outpatients.

PMID- 11974238
TI  - Educational support for nursing and midwifery students with dyslexia.
AB  - AIM: This article sets out to begin the process of discussing and investigating
      the support of nursing students and midwives with dyslexia. METHOD: The method is
      informed by grounded theory using a survey of universities through email contact
      with members of the Council of Deans (CoD). RESULTS: Twenty eight universities
      responded to the survey, representing 46 per cent of the CoD membership and 40
      per cent of the universities offering nursing and midwifery courses. The results
      show a wide variation of support available to students within financial
      constraints. Many universities offer support funded by top-slicing or goodwill
      gestures. CONCLUSION: Although concentrating on academic support, there are
      implications for practitioners who support students on clinical placements.

PMID- 11974240
TI  - Practical stoma care.
AB  - Patricia Black looks at the reasons behind and management of different types of
      stoma as well as outlining some of the possible problems associated with stomas.
      She emphasises the importance of caring for a stoma patient's psychological as
      well as physical wellbeing.

PMID- 11974244
TI  - Rich pickings.

PMID- 11974239
TI  - National service frameworks: what are they?
AB  - This article describes policy developments surrounding the creation of national
      service frameworks. The national service framework for mental health is used as
      an example to highlight the content of the framework and the way it has been
      received.

PMID- 11974245
TI  - Research: time for some executive action.

PMID- 11974246
TI  - On the home front.

PMID- 11974247
TI  - Definitely no wings.

PMID- 11974248
TI  - Tapping into talent.

PMID- 11974249
TI  - Back on the payroll.

PMID- 11974250
TI  - Bottoms up at 6 am.

PMID- 11974251
TI  - Flexible friends.

PMID- 11974252
TI  - Home remedies.

PMID- 11974253
TI  - Coming to terms.

PMID- 11974261
TI  - Nurse retention, transfer and migration.

PMID- 11974262
TI  - Organisational culture and consultant nurse outcomes: Part 1. Organisational
      culture.
AB  - AIMS: The aim of this three-year study was to operationalize the role of a
      consultant nurse and, in so doing, facilitate the development of nurses and
      nursing for the purpose of providing better patient services. METHODOLOGY: Action
      research was used because it focuses on developing practitioners, developing
      practice and contributing to understanding both the phenomena being studied and
      the processes being used. RESULTS: The role of leadership is recognised as key to
      bringing about cultural change, as is the use of approaches that clarify values
      and highlight the contradiction between espoused culture and culture in practice.
      CONCLUSION: The resulting culture had a positive impact on the unit in which the
      consultant nurse was based, on practitioners and their practice, and also on the
      trust. A number of factors, including transformational leadership, other
      facilitative processes, expertise in the practice of nursing, and other subroles
      of the consultant nurse were shown to be influential. This article explores the
      concept of organisational culture, and a second article to be published next
      week, discusses the consultant nurse outcomes.

PMID- 11974263
TI  - Is advocacy at the heart of professional practice?
AB  - This article considers the meaning of advocacy and the various forms of advocacy
      in existence. The author discusses whether the nursing profession sees advocacy
      as being at the heart of professional practice. Some of the risks that may result
      from advocacy are also outlined.

PMID- 11974265
TI  - Risk assessment in suprapubic catheterisation.
AB  - There are certain risk factors surrounding suprapubic bladder drainage and
      catheterisation. This article considers clinical indications and
      contraindications to suprapubic catheterisation. The advantages and disadvantages
      are discussed along with general care issues.

PMID- 11974266
TI  - Stress incontinence in younger women: prevention and treatment.
AB  - Urinary stress incontinence is prevalent in older people, but it has also been
      found to affect fit nulliparous women. Building pelvic floor muscles with pelvic
      muscle exercises helps to treat stress incontinence in women, but if exercises
      are begun at an early age, it is also effective in reducing the incidence of
      stress incontinence later in life.

PMID- 11974270
TI  - To the marrow.

PMID- 11974271
TI  - Full marks.

PMID- 11974278
TI  - Breaking down the boundaries.

PMID- 11974279
TI  - Gender politics.

PMID- 11974280
TI  - Bringing careers to life.

PMID- 11974281
TI  - On a sex drive. Interview by Charlotte Alderman.

PMID- 11974282
TI  - The Bombay fix. Interview by Charlotte Alderman.

PMID- 11974283
TI  - A winning formula.

PMID- 11974284
TI  - For what it's worth.

PMID- 11974286
TI  - Single minded.

PMID- 11974287
TI  - As one door closes....

PMID- 11974290
TI  - New cleaning guidelines for Propulse ear syringe.

PMID- 11974291
TI  - 1. Taking blood pressure.

PMID- 11974293
TI  - Nursing and the European Union.

PMID- 11974294
TI  - Using a patient satisfaction survey to close the theory-practice gap.
AB  - AIM: The objective of this study was to determine whether a patient satisfaction
      survey could be used as a research tool to improve nursing practice. METHOD: A
      postal questionnaire was sent to patients after discharge. Questions covered
      primary nursing, information, ward environment, discharge planning and social
      activities. RESULTS: A number of respondents were dissatisfied with the
      information they had received and with their lack of involvement in decisions
      about care. This was often correlated with lack of primary nurse recognition. The
      role of the associate nurse was poorly understood. There were high levels of
      satisfaction with discharge procedures, but little enthusiasm for the
      introduction of an activities programme. CONCLUSION: The results highlighted
      areas where changes were needed. This resulted in a nurse-led programme of
      managed change, including making all experienced D and E grade nurses primary
      nurses, improving information provision, and involving patients in the decision
      making process.

PMID- 11974295
TI  - Contraception: the changing needs of women throughout the reproductive years.
AB  - The contraceptive needs of women often change as they get older. Dinah Gould
      discusses the reasons behind this and reviews the different methods of
      contraception currently available.

PMID- 11974300
TI  - Time to pay up.

PMID- 11974301
TI  - Leading the way.

PMID- 11974302
TI  - Equal access.

PMID- 11974303
TI  - A little help from your PALs.

PMID- 11974304
TI  - No longer a poor relation.

PMID- 11974307
TI  - Bringing it all home.

PMID- 11974311
TI  - Back to the future.

PMID- 11974312
TI  - Out with the old, in with the new.

PMID- 11974313
TI  - The comfort zone.

PMID- 11974314
TI  - Hard times.

PMID- 11974315
TI  - Order out of chaos.

PMID- 11974316
TI  - Strike a balance.

PMID- 11974318
TI  - Take a break.

PMID- 11974320
TI  - Emergency services.

PMID- 11974327
TI  - Research and practice development in Scotland.

PMID- 11974328
TI  - Degree and diploma student nurse satisfaction levels.
AB  - AIM: The objective of this study was to identify differences between satisfaction
      levels of diploma and degree students on different branches of a common
      foundation programme. METHOD: Questionnaires were completed by 315 diploma and
      degree student nurses undertaking a common foundation programme at different
      intervals during training. RESULTS: Questionnaire responses showed different
      satisfaction levels in the three different branches. Mental health and child
      branch students were more aware of organisational problems than adult branch
      students. More child branch students were of the opinion that there were problems
      with placement preparation but gave teaching modules and lectures higher ratings.
      Mental health students were most dissatisfied with placement preparation and gave
      teaching modules and lectures lower ratings. CONCLUSION: The results provide data
      in support of the argument that students on child and mental health branches find
      the CFP less well organised for them and that degree students are more satisfied
      with the current standard of teaching and personal support.

PMID- 11974330
TI  - The use of leg lifting equipment.
AB  - This article discusses the manual handling risks associated with lifting
      patients' legs and describes equipment designed to minimise these risks. The
      findings of an evaluation of leg lifters are summarised and the potential
      benefits and limitations of this equipment for nursing practice are highlighted.

PMID- 11974331
TI  - Clinical trials: a journey of discovery.
AB  - This article provides an overview of clinical trials. Its aim is to give nurses
      an understanding of the international standards and regulatory procedures that
      guide clinical trials research, so that they will be able to assess critically
      the relative value of research outcomes.

PMID- 11974332
TI  - Sexually transmitted infections and older people.
AB  - Sexually transmitted infection (STI) remains a taboo subject when associated with
      older people. Elizabeth Grigg advises nurses to consider, without prejudice, the
      possibility of STI in older people.

PMID- 11974340
TI  - Taking charge.

PMID- 11974339
TI  - The nursefinder. Interview by Colin Parish.

PMID- 11974342
TI  - My double life. Interview by Charlotte Alderman.

PMID- 11974341
TI  - In defence of matron. Interview by John Naish.

PMID- 11974343
TI  - Happy together.

PMID- 11974344
TI  - Talking about cancer.

PMID- 11974345
TI  - Label conscious.

PMID- 11974346
TI  - Never say die?

PMID- 11974347
TI  - Comfort zone.

PMID- 11974351
TI  - Fitness for practice and purpose.

PMID- 11974352
TI  - Patient information on post-operative sickness.
AB  - AIM: To determine the amount of information patients received on post-operative
      nausea and vomiting and whether this could be improved. METHOD: A convenience
      sample of 140 post-operative patients was questioned. The patients were asked
      whether they had received any information, whether they thought information
      provision could be improved, whether an information leaflet would be useful and
      what information could be included. This led to a patient information leaflet
      being designed and piloted with 30 patients. A clear policy for patient education
      and staff training was also drawn up and a second audit was later carried out
      with 150 patients. RESULTS: About half the patients questioned in the first audit
      had not received any information, but thought that a patient information leaflet
      would be useful. On re-audit, 86 per cent of patients questioned had received
      information. Approximately half had the new patient information leaflet and only
      four did not receive any information. About 80 per cent of patients no longer
      thought it important to improve the information provision. CONCLUSION: This study
      showed that addressing information provision on post-operative nausea and
      vomiting with the use of audit led to a vast improvement in patient satisfaction
      with the amount of information they received.

PMID- 11974353
TI  - Understanding shock.
AB  - Shock is a serious condition that involves many organs of the body and must be
      treated immediately to ensure that the patient recovers. Timothy Collins provides
      a guide to shock, including the different types, the signs and symptoms and
      appropriate nursing care.

PMID- 11974355
TI  - An empirical investigation of pressure ulcer risk factors.
AB  - Despite many improvements in practice, pressure ulcers continue to be a source of
      concern to nurses and distress to patients. Clearly, there are no simple
      solutions to this problem and it is necessary to improve our understanding of
      pressure ulcer epidemiology and the effectiveness of preventive methods to
      continue to progress. Risk assessment is an important aspect of such work and
      forms the topic of this article. The authors first consider some of the
      difficulties associated with risk assessment and suggest that progress requires
      the use of multivariate statistical methods. They then describe the difficulty of
      comparing existing studies, which gives rise to the need for further work. A
      description of the study currently being undertaken follows, together with a
      presentation of the preliminary findings and a discussion of their implications
      for practice.

PMID- 11974356
TI  - Mixing and matching dressing products.
AB  - The reality of wound management in clinical practice leaves a lot to be desired
      in relation to dressing selection and use. Maureen Benbow highlights some of the
      problems currently being encountered in relation to good wound management
      practice and illustrates good practice with a particularly difficult case study.
      A basic understanding of patient assessment, wound assessment, dressing
      properties and their appropriateness at different stages of healing and for
      differing clinical appearances is essential to achieving success in wound and
      patient management. The author uses an unusual case study to illustrate the
      thinking and informed decision-making behind the choice of dressings used in
      combination. The issues to be addressed in relation to the management of wounds
      generally reflect the professional accountability of nurses and how they try to
      avoid harming the patient, the cost implications of dressings, their efficacy and
      clinical effectiveness and how practice can be improved.

PMID- 11974359
TI  - Dressing selection for the treatment of coumarin necrosis.
AB  - The correct dressing selection is of vital importance in producing as rapid a
      healing response as possible. John Timmons demonstrates the effects of a new
      dressing for the treatment of coumarin necrosis. Coloplast, the manufacturers of
      the dressing, Biatain Adhesive, supported the author while he was treating the
      patient.

PMID- 11974361
TI  - All in a day in A&E.

PMID- 11974362
TI  - Working in harmony.

PMID- 11974364
TI  - Political but not partisan. Interview by Pat Healy.

PMID- 11974365
TI  - A personal question. NHS Plan.

PMID- 11974366
TI  - Practising at a higher level. Interview by Alison Moore.

PMID- 11974368
TI  - Special delivery.

PMID- 11974367
TI  - Team spirit. Interview by Charlotte Alderman.

PMID- 11974369
TI  - First knight. Interview by Alison Moore.

PMID- 11974370
TI  - Digging ourselves out.

PMID- 11974371
TI  - No cause, no cure.

PMID- 11974372
TI  - In the right vein.

PMID- 11974374
TI  - Employment brief.

PMID- 11974375
TI  - Health effects of internal rotation of shifts.
AB  - BACKGROUND: Shirley Learthart examines the potential adverse effects to health of
      working on rotating shifts. CONCLUSION: Many studies indicate that shift work can
      cause health problems, including increased risk of coronary heart disease.
      Internal rotation is the reason given by many nurses for leaving the profession.

PMID- 11974376
TI  - Working together to improve record keeping.
AB  - Implementing changes in a hospital setting requires a structured approach to
      change management. This article describes the process of a project undertaken to
      improve record keeping in a children's hospital.

PMID- 11974377
TI  - Good practice in continence services.
AB  - The Department of Health, England, issued new guidance on continence services
      earlier this year. Sue Thomas examines the guidelines with a view to the future
      of continence care.

PMID- 11974378
TI  - Management of bowel dysfunction: evacuation difficulties.
AB  - Bowel dysfunction affects many people and encompasses a variety of problems. This
      article examines the different forms of bowel dysfunction and considers the
      nurse's role in caring for patients with this disorder, including manual
      evacuation.

PMID- 11974382
TI  - Use this guide to improve analysis of risk contracts.

PMID- 11974383
TI  - Ambulatory surgery centers receiving cap, but how much?

PMID- 11974384
TI  - Study: cost cuts, high quality not mutually exclusive.

PMID- 11974385
TI  - California HMO enrollment falls below 50%--now what?

PMID- 11974386
TI  - Violaceous lesions on the heel. Skin condition of the foot can be prevented and
      will resolve without medication.

PMID- 11974388
TI  - Handy tools for making home visits.

PMID- 11974387
TI  - Prevention for the older woman. A practical guide to prevention and treatment of
      osteoporosis.
AB  - Osteoporosis causes approximately 1.5 million low-trauma fracture per year, and
      at all ages the incidence of fracture is higher in women than in men. Risk
      factors for osteoporotic fractures in postmenopausal women include family history
      of bone fracture, ethnicity, and weight < 127 pounds. Densitometry is used to
      diagnose osteoporosis and can be performed at intervals to monitor bone density
      during treatment. The older woman's diet should, in general, include 1,200 to
      1,500 mg of calcium and 400 to 800 IU of vitamin D. Estrogens, bisphosphonates,
      selective estrogen receptor modulators, calcitonin, and exogenous parathyroid
      hormone are pharmacologic therapy options that can preserve and increase bone
      mass and reduce the risk of fracture.

PMID- 11974389
TI  - Agitation. How to manage behavior disturbances in the older patient with
      dementia.
AB  - Behavior disturbances are common among persons with dementia and can be
      clinically challenging to manage. Delusions and hallucinations, aggression and
      combativeness, sleep disorders, anxiety, and depression--collectively
      characterized as agitation--are among the commonly occurring behavioral problems
      affecting persons with dementia. Agitation can be precipitated by undiagnosed
      medical problems or pain, drug interactions, environmental or social triggers
      (unpleasant experiences, overstimulation, unwanted care), poor sleep, delirium,
      and depression. Effective management involves behavioral assessment and
      pharmacotherapy with antipsychotics (neuroleptics), antidepressants, and mood
      stabilizers.

PMID- 11974390
TI  - Geriatric hearing loss. Understanding the causes and providing appropriate
      treatment.

PMID- 11974391
TI  - The unreliable informant. Bad information hinders appropriate patient care.

PMID- 11974392
TI  - Keeping different kinds of vows.

PMID- 11974393
TI  - Oxy's offspring.

PMID- 11974394
TI  - Hepatitis C. The insidious spread of a killer virus.

PMID- 11974395
TI  - Risking life to give life.

PMID- 11974396
TI  - The prostate plan.

PMID- 11974397
TI  - Say, can I get glossies of my colonoscopy? New services keep digital archives of
      your medical tests.

PMID- 11974398
TI  - Who decides the value of drugs?

PMID- 11974399
TI  - Medication safety. Bar coding: the forgotten technology.

PMID- 11974400
TI  - Insurance. The fear of tier.

PMID- 11974401
TI  - Employee satisfaction. A happy workplace.

PMID- 11974402
TI  - 1Q[3a]. Do hospitals get a fair shake in the media?

PMID- 11974403
TI  - The problem with pitches.

PMID- 11974404
TI  - Eyes down, heart up.

PMID- 11974405
TI  - Dr. Discontent.
AB  - Physicians are angry, that that's bad news for hospitals. Increasingly, doctors
      are unable to pay soaring liability insurance premiuyms, are refusing to accept
      new Medicaid and Medicare patients, and are balking at taking ED calls. What's
      more, many physicians are setting up niche facilities that compete directly with
      hospitals in the most lucrative service lines.

PMID- 11974409
TI  - Nowhere else to turn. As the ax falls on mental health funding, hospital EDs fill
      the gap--reluctantly.
AB  - As the ax falls on mental health funding, state mental hospitals are closing and
      investor-owned psychiatric organizations are filing for bankruptcy or shifting
      their focus to more lucrative general acute care services. That leaves patients-
      many of them uninsured--with nowhere to seek help except hospital emergency
      departments.

PMID- 11974410
TI  - Rural renewal. As momentum builds, critical access hospsital program shows signs
      of success.
AB  - The critical access hospital program looks like a success so far, keeping
      vulnerable rural facilities from closing and maintaining a continuum of care in
      communities where the next nearest hospital might be hours away. Although
      conversions can be bumpy, one in four rural hospitals is now a CAH and that
      number is increasing.

PMID- 11974411
TI  - Medication safety. A framework for change.
AB  - Innovative health care organizations are leading the way in taking medication
      safety from concept to reality. This month's fold-out section looks at those
      programs and provides tools for you to implement a medication safety program at
      your hospital.

PMID- 11974412
TI  - A business imperative.
AB  - Diversity is no longer optional; it's necessary for health care institutions that
      want to succeed. There's no one-size-fits-all approach, but good strategies have
      a few things in common.

PMID- 11974413
TI  - The future of family planning programs.
AB  - National family planning programs have been an important instrument in
      accelerating global fertility decline and in restricting ultimate world
      population to a level probably below ten billion. They began to come into being
      after 1950 and will probably go out of existence in most of the world's regions
      by 2050. The archetypal programs were instituted in Asia and North Africa. The
      end of the twentieth century is an appropriate half-way mark at which to evaluate
      the twentieth-century programs and to assess what changes in them will be needed
      for the twenty-first century. Some changes are necessary because dramatic events
      have occurred: (1) long-term replacement-level fertility has been attained in
      most of East Asia and some of Southeast Asia, and accordingly, some programs
      there are being phased out; (2) mainland South Asian fertility has been slower to
      decline; (3) international donor funding is diminishing and may not be
      significant during much of the twenty-first century; (4) the 1994 International
      Conference on Population and Development held in Cairo called for a radical
      change in programs away from demographic aims and toward reproductive health and
      the improvement of the situation of women; and (5) the future family planning
      frontier will be sub-Saharan Africa, for which radically new types of programs
      may have to be developed. These issues were discussed in January 2000 at a
      conference held in Dhaka, Bangladesh. A selection of contributions to the
      conference is published here. This article provides an overview of the issues
      based partly on this selection and partly on the discussions that took place at
      the conference.

PMID- 11974414
TI  - China's family planning policy: an overview of its past and future.
AB  - This article provides a broad overview of China's family planning policy during
      the last three decades, highlighting key trends and goals of the program at
      national and provincial levels. It focuses on the administrative, economic,
      cultural, and other factors that have helped or hindered the family planning
      effort and reviews the impact of the program on the provincial population. A key
      question is whether the policy of strict fertility control will remain relevant
      and enforceable as population growth slows, as controlling private life becomes
      increasingly problematic for the government, and as new demographic problems (for
      example, aging) emerge.

PMID- 11974415
TI  - United Nations population conferences: shaping the policy agenda for the twenty
      first century.
AB  - Population conferences have evolved through three overlapping stages, each stage
      reflecting a different perspective on the relationship between national policy
      formulation and the international system. Initially, at Rome in 1954 and in
      Belgrade in 1965, participants were invited on the basis of their expertise and
      were not expected to represent their governments. By the time of the Bucharest
      Conference in 1974, the United Nations, in an attempt to give conferences a
      greater role in shaping population policy and to inspire member governments to
      show greater concern for their own population problems, decided that conferences
      would be intergovernmental gatherings and that national delegations would be
      selected by governments. The effect of this change was that governments gave less
      weight to scientific expertise and, conversely, greater weight to political and
      bureaucratic considerations. At the present time, although conferences remain
      intergovernmental gatherings, the door has been opened for nongovernmental
      organizations--civil society--to play a more active role in the conference
      process and in deliberations. As conferences have become more inclusive, their
      focus has veered from what has conventionally been regarded as population
      concerns. The changing composition of participants at UN conferences has had the
      effect of altering the policy agenda in the international population field and,
      as some have argued since Cairo, has redefined the meaning of population.
      Conferences in the twenty-first century likely will be compelled to confront
      diverse demographic problems in addition to social issues demanding the attention
      of the political system at every level.

PMID- 11974416
TI  - Asia's family planning programs as low fertility is attained.
AB  - The dramatic demographic changes in Asia during the three decades from 1970 to
      the end of the twentieth century were matched by major changes in government
      population policies and programs. Fertility declines occurred in widely different
      economic, sociocultural, and political settings. The extent to which they were
      attributable to family planning programs, established in most countries of the
      region by 1970, is hotly debated. The 1970s were the heyday of family planning
      programs, which were created in a climate of urgency because of concerns over the
      "population explosion." Issues faced by programs at that time are discussed. Over
      time, programs generally have moved to a simpler "service" approach. As
      increasing numbers of countries reach replacement-level fertility, and as
      policies are formed against the background of the 1994 International Conference
      on Population and Development held in Cairo, the role of family planning programs
      is increasingly debated and questioned. This article examines the responses of
      Asian countries and the population challenges that remain.

PMID- 11974417
TI  - Future trends in contraceptive prevalence and method mix in the developing world.
AB  - This study reviews existing methodologies for projecting future trends in
      contraception, evaluates the validity of the assumptions underlying these
      projections, proposes methodological improvements, and assesses the prospects for
      new methods of contraception in the coming decade. Demand for contraception can
      be expected to continue to rise rapidly for the next few decades as populations
      continue to grow and fertility declines to approach replacement level. As a
      result of these trends, the number of contraceptive users in the developing world
      is expected to rise from 549 to 816 million during the next 25 years, according
      to the most recent UN projection. An examination of the projection methodology
      found it to be reasonable. Projecting the future distribution of specific
      contraceptive methods is more difficult. Method choice is affected by trends in
      several factors, including access to different methods, user characteristics, and
      technology. The procedure employed by the Futures Group to project method mix was
      found to be less than optimally designed, and a new methodology is, therefore,
      proposed.

PMID- 11974418
TI  - Policy implications of the next world demographic transition.
AB  - Although the world demographic transition from high to low fertility appears to
      be nearing its completion, observed in perspective, this is the latest in a
      series of such transitions stretching back into prehistory. A stable new
      equilibrium is far from inevitable; indeed, it is unlikely. Many countries are
      experiencing below-replacement-level fertility, and this trend is spreading.
      Couples are now able to choose their family size, free of the traditional
      pressures to bear children that was characteristic of most traditional societies.
      In fact, most societal pressures for the last generation have been distinctly
      antinatalist, in response to the enormous attention paid by the media to the
      "population bomb" agenda. This antinatalist attitude is changing, however, and
      what seems more likely than either a stationary or declining world population is
      a new growth cycle reflecting a resurgence of fertility as a response to growing
      material affluence and potential technological mastery of environmental
      challenges. Societal pressures and policies will play a role in this transition
      as they did in earlier ones.

PMID- 11974419
TI  - Transforming family planning services in the Latin American and Caribbean region.
AB  - The 1994 International Conference on Population and Development held in Cairo has
      generated widespread commitment to changing family planning programs from
      categorical and medically focused service organizations to reproductive health
      initiatives that embrace a wide range of social and human services. This article
      uses qualitative data analysis to review the experience of nine family planning
      association projects in the Latin American and Caribbean region that have made a
      successful organizational transition from services focused on family planning to
      a gender-based and sexual health approach. A conceptual framework is proposed,
      including factors external to the organization. Factors that can promote a pilot
      intervention's becoming fully institutionalized include: the need for commitment
      from high-level staff and members of the board of directors, the creation of
      partnerships with other agencies, and an emphasis on monitoring and evaluation.
      Lessons from this experience and their potential relevance to other settings are
      reviewed and discussed.

PMID- 11974420
TI  - Facilitating large-scale transitions to quality of care: an idea whose time has
      come.
AB  - In the field of reproductive health, investigation of the transfer of knowledge
      gained from demonstration and pilot projects to large public-sector programs
      typically has not been considered a relevant domain for research or other
      investigation. This article draws on a range of research in the social sciences
      and presents two frameworks for understanding the critical attributes of
      successful expansion of small-scale innovations. Seven key lessons are developed
      using examples from family planning where scaling up was an explicit objective,
      including the early Taichung Study of Taiwan, the Chinese Experiment in Quality
      of Care, the Bangladesh MCH-FP Extension Project, the Navrongo Project in Ghana,
      and the Reprolatina Project in Brazil. Unless small, innovative projects concern
      themselves from the outset with determining how their innovations can be put to
      use on a larger scale, they risk remaining irrelevant for policy and program
      development.

PMID- 11974421
TI  - Africa: the new family planning frontier.
AB  - Sub-Saharan Africa will be the family planning frontier of the twenty-first
      century. Fertility levels and population growth rates are still high, and family
      planning programs suited to the region are still being developed. Nevertheless,
      by the end of the twentieth century, fertility transition was under way in
      Southern Africa and a few countries elsewhere. Successful regional family
      planning in the twenty-first century will depend upon stronger political
      leadership, the development of family planning programs that meet the needs of
      all segments of society and not only currently married women, assistance to the
      market, and a recognition of the central importance of hormonal methods,
      especially injectables. Problems include stagnation in economic growth and in
      child mortality decline, as well as the persistence of the AIDS epidemic.

PMID- 11974422
TI  - Reconsidering the doorstep-delivery system in the Bangladesh Family Planning
      Program.
AB  - The government of Bangladesh is currently testing and implementing strategies to
      change its family planning program from a reliance on field-workers who conduct
      home visits to a conventional fixed-site delivery system. Researchers have made
      two suggestions: First, the program should encourage women to switch from
      nonclinical methods delivered by family planning workers to more cost-effective
      clinical methods such as sterilization, and second, field-workers should not be
      resupplying nonclinical methods, but should focus their attention on motivating
      nonusers to practice contraception. Longitudinal data from the Maternal and Child
      Health-Family Planning Extension Project of the International Centre for
      Diarrhoeal Disease Research, Bangladesh, are analyzed to show that a better
      strategy might be to target visits to women according to their educational level
      and area of residence. For uneducated women living far from clinics, access to
      contraceptives is likely to be a problem, and home visits for resupply might have
      a larger impact on the contraceptive prevalence rate than would field-workers'
      visits to motivate nonusers.

PMID- 11974423
TI  - Psychomotor function and learning clinical skills: a critical appraisal.
AB  - The practice of clinical medicine involves performing a large number of practical
      procedures so that psychomotor function is of considerable importance,
      particularly to trainees mastering new skills. Performance of motor skills by
      trainees is usually assessed by faculty in a random, unorganised, subjective
      manner without clearly stated criteria of satisfactory performance. This review
      discusses objective assessment of motor skills utilising psychometric principles
      in anaesthesia and surgery. In addition, the role of simulators will be discussed
      within the context of learning new motor skills.

PMID- 11974424
TI  - Tumour markers--magic or menace?
AB  - Breast cancer follow-up is aimed at the detection of metastatic disease at a
      stage when it can still be treated. Traditionally this has been done on a
      symptomatic basis confirmed by UICC criteria. By inference, tumour burden by this
      time is likely to be high, and therefore any therapy possibly less effective.
      Breast Serum Tumour Marker estimation, while disease volume is still low, has
      been shown in a District General Hospital setting to allow early treatment and
      monitor efficacy of therapy. A randomised multi-centre study is essential to
      determine whether these investigations are sensible and life-saving or costly and
      confusing.

PMID- 11974425
TI  - Restorative proctocolectomy in UK servicemen.
AB  - OBJECTIVE: To investigate the outcome of restorative proctocolectomy (RPC) in UK
      Servicemen and to determine the compatibility of this procedure with Service
      life. PATIENTS: All Servicemen undergoing restorative proctocolectomy for
      ulcerative colitis (UC) or familial adenomatous polyposis (FAP) up to December
      31st 2000 were identified from Service records. Patients were reviewed by direct
      or telephone interview. Pouch function, military duties, medical category or
      reasons for discharge from the Service were recorded. RESULTS: Fifteen Servicemen
      (6 Royal Navy, 6 Army, 3 RAF), mean age 30 years, underwent RPC for UC (14) or
      FAP (1) with a median follow-up of 74 months. Eight remain in their Service, five
      of whom carry out full duties and three restricted duties. Of the seven who have
      left the Services only one was medically unfit to continue due to poor pouch
      function whilst six left voluntarily to pursue active civilian careers. Fourteen
      patients have acceptable pouch function; one pouch has been excised for
      intractable pouchitis. CONCLUSIONS: Restorative proctocolectomy is compatible
      with Service life and most individuals are capable of fulfilling active
      unrestricted military duties.

PMID- 11974426
TI  - A critical review of psychological debriefing: the management of psychological
      health after traumatic experiences.
AB  - Psychological debriefing cannot be considered safe and thus it should not be
      routinely used. There is evidence to suggest that risk assessment for adverse
      psychological outcomes after traumatic events may be a useful management
      strategy. This process is ongoing with the Royal Marines and is being evaluated.

PMID- 11974427
TI  - Is vaccination against meningitis useful? The findings of an investigation in the
      Sherbrooke region, Quebec.

PMID- 11974428
TI  - Cat-scratch disease in children--Texas, September 2000 to August 2001.

PMID- 11974429
TI  - [Look diagnosis in pediatrics. What to know about swallowed foreign bodies].

PMID- 11974430
TI  - [The patient with hematemesis. What to do?].
AB  - In patients with hematemesis an emergency endoscopy has to be done as soon as
      possible. In ulcer disease emergency endoscopic treatment is indicated in ulcers
      with active bleeding or with visible vessels in the base of the ulcer. There is
      no significant difference in the efficacy between the various endoscopic methods
      of hemostasis. Gold standard in the treatment of acute variceal bleeding is the
      hemostasis by endoscopic ligation or sclerotherapy. Because of the very low
      complication rate variceal ligation is the therapy of choice in the prevention of
      variceal rebleeding. Especially in patients with preexisting portal hypertensive
      gastropathy an additional therapy with beta-blocker is recommended. In the
      prevention of first variceal bleeding a combination therapy with beta-blocker and
      nitrate is indicated in patients with big varices with red colour signs and in
      patients with decompensated liver cirrhosis (Child B).

PMID- 11974432
TI  - [Lung function measurements with portable spirometers in children].
AB  - In the majority of patients with respiratory disease, the most important
      diagnostic information can be obtained just by taking a thorough medical history
      and appraising the general clinical status. Lung function is a valuable tool in
      routine practice for assessing the general status at the beginning of treatment,
      for evaluating the clinical course and for documenting the response to therapy.
      The parameters measured by spirometry are read as volume (liter) or volume per
      unit of time (flow). If a spirometer is used in pediatrics, its measurements
      should be linear, within the range of the flow rates achieved by children.
      Spirometry does not provide information about the respiratory status in the
      resting state. If pulmonary overinflation or restriction is suspected (for
      example in patients with cystic fibrosis), a whole-body plethysmograph must be
      performed in addition to spirometry. Because their cooperation is required,
      children under the age of 5-6 cannot be given spirometric examinations. The
      younger the subject, the more important it is that the examiner has experience in
      dealing with children as well as experience in interpreting lung function
      readings. By far, not all children have the physical or pulmonary development
      required to understand how to exhale deeply or forcibly enough. As soon as they
      start breathing consciously, they will tend to breath flatter and quicker.
      Therefore, it is worth while for the examining physician to perform the breathing
      maneuver several times himself in front of the child to show them how it is done
      and have them practice before the measurement. It is imperative that a curve of
      the dynamics of the resulting time/flow volume be made available. The curve
      configuration enables diagnosis and allows assessment of the patient's
      cooperation. The readings are then used for quantifying analysis.

PMID- 11974431
TI  - [Increased blood sugar in type 2 diabetes mellitus: what now?].
AB  - There are various reasons for an increased diabetes with type-2 patients. The
      most frequent reason for hyperglycemia is the metabolic insulin resistance often
      resulting from a sustaining bad control of metabolism. The problem of insulin
      resistance can be overcome by making use of high doses of short acting insulin.
      In case of a subcutaneous insulin resistance, a rare type of insulin resistance,
      normalising blood sugar can only be achieved by intravenous application of
      insulin. In many cases there are quite simple reasons for insulin resistance. An
      erroneous technique of insulin injection is very often attributable for an
      abnormal need of insulin. With type 2 patients distinctly oscillating blood sugar
      is anything but normal. Besides a gastroparesis, one needs, in this case, take
      account of latent autoimmune diabetes of adults (LADA). The most important
      reasons for hypoglycemia with type-2 diabetes are the following: sulfonylurea and
      high doses of intermediate-acting insulin.

PMID- 11974433
TI  - [Update on childhood immunization in Switzerland].
AB  - The recommendations for routine childhood immunizations undergo continuous re
      evaluation and are periodically amended. As a result of the near complete
      elimination of wild-type poliomyelitis, the oral poliomyelitis live vaccine (OPV)
      has been replaced by the inactivated vaccine (IPV) for the primary series in
      infancy. Recent seroepidemiologic data on the dynamics of decay of maternal
      measles antibodies in infants may lead to the recommendation of administering the
      first dose of the measles mumps rubella (MMR) vaccine at twelve months rather
      than at 15 to 23 months of age. The recently introduced hexavalent vaccines for
      the primary series in infancy provide immunization against hepatitis B without
      the need for additional injections. Finally, the introduction of pneumococcal
      conjugate vaccines, which are highly efficacious in infants and young children,
      will provide the opportunity for successful prevention of vaccine-type invasive
      pneumococcal infections.

PMID- 11974434
TI  - [Refractory hypertension: evaluation and treatment].
AB  - Refractory hypertension is common in patients non-compliant with antihypertensive
      therapy, in obese and stroke patients, and due to drug interactions with
      nonsteroidal anti-inflammatory drugs or excessive alcohol intake. The evaluation
      and management of these pitfalls as well as the causes of secondary hypertension
      are discussed.

PMID- 11974435
TI  - [Swiss psychiatry and National mental health. The Section "Mental Health" in
      Hygiene and Sports Exhibition 1931].

PMID- 11974436
TI  - [Aldicarb poisoning: review of cases in the North of France between 1998 and
      2001].
AB  - Among the 2,726 cases of human pesticide poisoning collected at the Poison Centre
      of Lille from January 1998 to May 2001, 39 cases were related to the ingestion of
      aldicarb. Analysis of the circumstances found a suicide attempts in 33 cases and
      an accidental ingestion in 6 cases. The sex-ratio was 31 men for 8 women, mean
      age was of 36.6 years (15 months--77 years). Thirty one poisoning were
      symptomatic with muscarinic signs (20 cases), digestive (15 cases), neurological
      (8 cases), nicotinic signs (6 cases). Treatment was based on digestive evacuation
      (14 cases), administration of activated charcoal (14 cases), atropine (7 cases),
      pralidoxime (1 case), preservative vital functions by intubation and ventilation
      (7 cases). Sedation was necessary in 4 cases. Hospitalization was necessary in 34
      cases. The Poison Severity Score was estimated at 0 (any gravity) in 5 cases, 1
      (weak) in 12 cases, 2 (moderate) in 7 cases, 3 (severe) in 8 cases and 4 (lethal)
      in 2 cases. In one of deaths, aldicarb was determined by HPLC-DAD in blood (6.04
      micrograms/ml), urines (1.88 micrograms/ml) and gastric contents (3.98
      micrograms/ml). These concentrations are the most important ever described in the
      literature. Aldicarb is the most toxic carbamate insecticide for human.

PMID- 11974437
TI  - [Determination of monoester metabolites of butylbenzyl phthalate (BBP) by GC-MS
      in the urine of exposed workers].
AB  - A method of analysis was developed to determine free and glucuronated monobutyl
      phthalate (BuP) and monobenzyl phthalate (BeP) in urine for the assessment of
      exposure of man to butylbenzyl phthalate (BBP) in the workplace and in the
      environment. This method has also been applied in pharmacokinetic studies in
      experimental animals and the determination in urine of exposed workers. Urine
      samples are first subjected to enzymatic hydrolysis with beta-glucuronidase to
      enable the measurement of the total amount of monophthalates excreted. A fraction
      of the hydrolysate is used for further analysis. Monohexyl phthalate is added as
      an internal standard and the hydrolysed urine extracted with a n
      hexane/dichloromethane mixture after acidification and saturation with salt. The
      organic fractions are washed, dehydrated and evaporated. The residue is
      methylated by means of diazomethane dissolved in diethylether, evaporated and
      further purified by extraction into n-hexane from an alkaline buffer. The organic
      fractions are evaporated and the residue redissolved in acetonitrile for analysis
      by ion trap GC-MS equipped with a 50 m apolar WCOT capillary column. TIC mass
      chromatograms are recorded from which SIM chromatograms can be derived
      electronically. The m/z values used are 91, 149, and 163 which provide a
      sufficient sensitive response and which are specific enough to pick up the
      methylated monophthalates under investigation. The quantitative limit of
      detection (LOQ) is 60 micrograms/L for BuP and BeP when using the Magnum ion Trap
      detector and 3 micrograms/L when using the Polaris Q in the splitless mode. The
      calibration curve in urine is linear from 120 micrograms/L to 50,000 micrograms/L
      with a coefficient of variation of less than 10%. In case of the Polaris Q
      linearity started from 10 micrograms/L. The recovery of the method is monitored
      by the response signal of the internal standard in the ion chromatogram. In the
      event of insufficient recovery the analysis is repeated. Variations in recovery
      are compensated by the internal standard of which the molecular structure is very
      similar to the ones of the monophthalates under investigation.

PMID- 11974438
TI  - [Endocrine disruption and organochlorine pesticides].
AB  - Xenoestrogens such organochlorine pesticides are known to induce changes in
      reproductive development, function or behaviour in wildlife. Because these
      compounds are able to modify the estrogens metabolism, or to compete with
      estradiol for binding to the estrogen receptor, it may be possible that these
      products affect the risk of developing impaired fertility, precocious puberty or
      some kinds of cancer in man.

PMID- 11974439
TI  - [Crime under the influence of psychoactive drugs: the problem of the duration of
      detection].
AB  - On a regular basis, the media presents the potential risks of the use of psycho
      active compounds, including misused pharmaceuticals (flunitrazepam, GHB) or drugs
      of abuse (cannabis, LSD, ecstasy). Ethanol is also frequently encountered. These
      drugs can be used for recreational purposes by addicts or can be observed after
      sexual assaults (drugs spiked in food). Forensic toxicology can be involved in
      several situations to document impairment, such as: crime under influence, date
      rape, driving under influence, psychiatric disorders, determination of the cause
      of death... In some particular situations, it can be very cautious to investigate
      exposure to psycho-active drugs, due to late sampling of biological specimens. To
      enhance the window of detection of 3 specific drugs, the authors propose the
      following: 1. Use of an ultra-sensitive technique, such as GC/MS/MS/NCI for 7
      aminoflunitrazepam; 2. Use of a cumulative specimen, such as sweat for GHB and 3.
      Use of a metabolite with a long half-life, such as ethyl glucuronide for ethanol.

PMID- 11974440
TI  - [Ketamine--dreams and realities].
AB  - Ketamine is an anaesthetic used in human medicine and veterinary practice,
      synthesised on 1962 and marketed on 1970 in France. Recreational uses were
      described during 1992 in the medical community and in 1996 in the dance settings.
      The chemical name of ketamine is 2--(2chlorophenyl)2-(methylamine)-cyclohexanone,
      an aryl cyclohexylamine, structurally related to phencyclidine. Ketamine is known
      under the following street names: Keta K, Kate, Special K, Vitamin K, la Golden,
      la Veterinaire. Ketamine is used intranasally, orally and intramusculary in
      recreational use. Ketamine is manufactured by the chemical industry. Due to the
      complicated synthesis, it is sold illicitly for recreational use. Ketamine is a
      dissociative drug, and the user enters in a psychedelic dream with
      hallucinations, floating sensation, feeling of dissociation of the mind from the
      body. The dream is forgotten, the user full in reality with loss of self control,
      risk of acute intoxication. In long-term exposure, tolerance, dependence,
      withdrawal signs and flash back are described. Ketamine trademarks are subject to
      control in France through medicine legislation Ketamine and its salts are subject
      to control under the national legislation on narcotics and psychotropics
      substance. From September 2001, the theft of medical and veterinary trademarks
      have to be declared to police, care health authority Pharmacy control authority
      and French Health Products Safety Agency.

PMID- 11974441
TI  - [Ma Huang, from dietary supplement to abuse].
AB  - Dietary supplements containing Ma Huang (chinease ephedra) are available on the
      web sites and dietary shops in USA. They are widely promoted and used as a mean
      of weight reduction and energy enhancement. They contain Ma Huang alone or
      combined with Guarana (caffeine), creatine, St John's wort, carnitine and are
      proposed with different labels. Numerous reports of adverse reactions and acute
      intoxication related to these products use were described in the medical
      literature. In the light of the severity of these cases, some of which resulted
      in permanent injury and death, the Food and Drug Administration has proposed
      limits on the dose and duration of use of such supplements. A review of 140
      reports submitted to the FDA between June 1997 and March 1999, 47% involved
      cardiovascular symptoms, 18% neurological symptoms. Severe hypertension was the
      single most frequent adverse effect followed by tachycardia, myocardial
      infarction, stroke, seizure. Ten events resulted in death and 13 produced
      permanent impairment. In France, ampleness of the use of dietary supplements
      containing ephedra alkaloids is unknown. Two French recent severe poisonings (one
      with "ripped Fuel" for losing weight and the other with "Energy pills" in a body
      builder) show that there is serious health risks for the chronic users. Dietary
      supplements are not subject to control under "la Direction Generale de la Sante".
      Informations for general public, medical community and health-care authorities
      are necessary to be aware of potential health hazards of these products use.

PMID- 11974442
TI  - [Use of gamma-hydroxybutyric acid (GHB) at rave parties and in date rape in
      France: myth of reality?].
AB  - Since many years gamma-hydroxybutyric acid (GHB) is presented as very popular in
      rave-parties and for bodybuilders. It seems to be a controversy between media
      coverage and the results of toxicological analysis done in high-level
      laboratories. In order to clarify this problem, we compiled the data of 6
      laboratories. They used the same analytical method by GC/MS. Depending the
      laboratory, the limit of detection was 1-2 micrograms/mL and the limit of
      quantification was 2.5-5 micrograms/mL. Two labs where looking for GHB in each
      forensic case (100 and 150 cases a year). Others labs performed GHB analysis only
      on specific request (each 10 cases a year). Mean time between ingestion of GHB
      and blood/urine sampling was 12-48 h. Mean time between sampling and analysis was
      much higher (a few hours to a few month. All samples were stored at +4 degrees C.
      Only 3 cases were considered as positive (blood GHB: 165, 132 and 114
      micrograms/mL, urine GHB: 7450 and 436 micrograms/mL) They were admitted in an
      hospital EU. Interpreting results remains very difficult because GHB is
      endogenous, present in blood and urine, and its half-life is very short. One has
      to report only "positive" GHB results when amounts are higher than 5
      micrograms/mL in blood and 10 micrograms/mL in urine. Obviously, forensic
      toxicologists have to play a very important part in diagnosis of GHB
      intoxications and estimating its frequency. Actually, because the lack of data in
      France, it is not possible to answer the question asked in the title of this
      paper.

PMID- 11974443
TI  - [New drugs at "rave parties": ketamine and prolintane].
AB  - "Rave parties", all-night dance parties based on "techno" music, represent an
      increasing phenomenon in France. "Rave drugs" refers to a wide variety of drugs
      used by the young participants owing to their hallucinogenic or stimulant
      effects. Uncertainties about the sources of these substances, the possible
      contaminants and the multiplicity of the associations make it difficult to
      evaluate the toxic consequences that might be expected in this particular
      context. This report presents toxicological cases documented by analytical
      findings in which two pharmacological agents abused in "rave parties" in South
      West of France were found. The day following a party, a 17 year-old girl showed a
      confused state with drowsiness and hallucinations. She confessed having consumed
      a white powder sold as "ecstasy", that sample analysis identified as pure
      ketamine. Ketamine is an anaesthetic agent primarily used in veterinary medicine
      and paediatrics. This drug seems to be abused, mainly by the intranasal route,
      owing to its hallucinogen effects. Its used in "rave-party" appears to be marked
      by unsuspected consumption. All long another party, a large quantity of orange
      tablets were sold and abused by several participants. Analysis performed on some
      fragments of these tablets revealed the presence of prolintane and ascorbic acid.
      Prolintane, an amphetamine-related substance, is a central nervous system
      stimulant. This compound is "freely" available in Spain in combination with
      several vitamins, under the form of tablets with orange coating named "Katovit"
      and sold at low price: 1.93 [symbol: see text]/20 tablets (200 mg of prolintane).

PMID- 11974444
TI  - [Rapid determination of propofol in biological specimens and hair by HS-GC/MS].
AB  - This paper proposes an original method for the determination of propofol in
      biological specimens. For example, hair specimens are cut into small pieces and
      incubated overnight in Soerensen buffer at 40 degrees C. After headspace
      preparation of the biological specimens spiked with tetrahydrofurane (internal
      standard), the analytes are transferred to the gas chromatograph and separated on
      a HP Wax capillary column. Detection is achieved in SIM mode (propofol: m/z 117,
      163 and 178) on a mass spectrometer operating in electronic impact mode. The
      developed procedure is easy (full-automated), rapid (no extraction- or
      derivatization-step), sensible and accurate. After validation of the analytical
      method (linearity, extraction recovery, repeatability, limit of detection), this
      new procedure was applied to forensic cases.

PMID- 11974445
TI  - [Fatal intoxication after accidental ingestion of viscous 2% lidocaine in a young
      child].
AB  - We report a case of fatal intoxication with 2% viscous lidocaine. A 18 month old
      infant was admitted after malaise and cardiorespiratory arrest at home. He was
      resuscitated, then seizures appeared before arrival at the hospital. Treatment
      was symptomatic, including cardiorespiratory resuscitation and administration of
      anticonvulsants. Identification of lidocaine and its metabolite
      monoethylglycinexylidide (MEGX) MEGX was performed after organic extraction by
      High Performance Liquid Chromatography (HPLC) with Diode Array Detection (DAD);
      the serum concentrations, determined by Fluorescence Polarisation Immuno Assay
      (FPIA), were: 1.1 micrograms/ml for lidocaine and 0.94 microgram/ml for MEGX (H +
      7) and 0.30 microgram/ml for the lidocaine (Day + 1). Neurotoxic manifestations
      appear at lower concentrations than cardiotoxic symptoms which are correlated
      with plasma levels of lidocaine. The toxic symptoms begin with headache,
      hallucinations, seizure, coma, respiratory arrest and circulatory collapse. The
      toxic symptoms can persist even after the decrease of lidocaine concentration
      under therapeutic levels. There is no antidote and acute lidocaine toxicity is
      managed with supportive therapy (diazepam for seizures, intubation, chronotropic
      agents). Considering the gravity of these poisonings which remain rare, the 2%
      viscous lidocaine prescription is forbidden for children under 6 years old.

PMID- 11974446
TI  - Suicide with remifentanil and midazolam: a case report.
AB  - BACKGROUND: Remifentanil (Ultiva) is a recently introduced esterase-metabolized
      potent opioid (EMO) mu-receptor agonist with a rapid onset and offset of action
      for use as part of general anaesthesia in association with isoflurane or propofol
      or with midazolam (Dormicum) and in combination with mivacurium. CASE REPORT: A
      nurse from the anaesthesiology department of a hospital was found dead at home
      with a syringe and empty vials of Ultiva (2 mg) and of Dormicum (1 mg/mL). At
      autopsy several injection sites were found on her body. Usual toxicology
      screening operated in our laboratory revealed only the presence of
      benzodiazepines in blood. Regarding the case history, we decided to adapt a
      method specially designed for remifentanil and its inactive metabolite testing.
      The analytes were isolated by SPE on a Clean-Screen column. After silylation with
      BSTFA with 1% TMCS, the analytes were detected by GC/MS-EI operating in the SIM
      mode. No Remifentanil could be detected, whereas the metabolite of remifentanil
      GR90291 was determined in femoral blood, liver, kidney and lung. Furthermore,
      midazolam could be detected in femoral and cardiac blood. Hair analysis of a
      segment of 5 cm revealed the presence of diazepam and midazolam, whereas neither
      remifentanil nor its metabolite could be detected.

PMID- 11974447
TI  - [Methemoglobinemia induced by repeated abuse of lidocaine viscous gel].
AB  - Lidocaine use may lead to methemoglobinemia. Lidocaine is clinically widely used
      as an anaesthesic drug, however its toxic effect is rare. We report a high
      methemoglobinemia level of 31.1% following repeated Xylocaine gel oral
      applications. New metabolic pathways of lidocaine have been reported leading to
      dimethylphenylhydroxylamine in humans. This metabolism is very similar to the
      aniline derivative ones, and may explain lidocaine methemoglobinemia effect.

PMID- 11974449
TI  - Effects of angle Class II, division 1 treatment with jumping-the-bite appliances.
      A longitudinal study.
AB  - AIM: The present study investigated treatment effects in patients with Angle
      Class II, Division 1 malocclusions treated with jumping-the-bite appliances on
      the basis of cast evaluation and lateral cephalometrics. RESULTS: A significant
      reduction in overjet (p < 0.001) and overbite (p < 0.01) occurred during the
      course of treatment. A significant reduction in the SNA-angle (p < 0.001) and
      increase in the SNB-angle (p < 0.001) led to a reduced ANB-angle (p < 0.001). The
      treatment effect on the maxilla was greater than on the mandible. A slight
      posterior rotation of the maxilla (p < 0.05) occurred whereas the other vertical
      relations did not change significantly. The upper incisors were significantly
      retruded (p < 0.001) while the lower incisors were increasingly protruded (p <
      0.001). The interincisal angle was not markedly altered.

PMID- 11974448
TI  - [Serial determination of crimidine by HPLC/SE/SM in a patient ingesting a "mouse
      trap"].
AB  - Crimidine (2 chloro, 4 methyl, 6 dimethyl amidopyrine) is a synthetic rodenticide
      which causes acute poisonings after oral ingestion in human. Major toxic effects
      are consciousness disorders, hypertonic coma and convulsions. Toxic level in
      human is about 5 mg/Kg. An intoxication case is reported. Five serums collected
      at different times were analyzed with HPLC/ES/MS. Crimidine was extracted with
      ethylacetate with recovery over 80%. Linearity was up to 800 micrograms/L. LOQ
      and LOD were 0.5 and 0.3 microgram/L respectively. The coefficients of variation
      were less than 10% for repeatability and reproductibility. Serum levels varied
      from 368 micrograms/L for H0 to 64 micrograms/L for H10 and elimination of
      crimidine was linear in time.

PMID- 11974450
TI  - Retention and stability--taking various treatment parameters into account.
AB  - PATIENTS AND METHOD: In order to assess stability after orthodontic treatment,
      132 patients who had been treated by one orthodontist in private practice were
      examined 6 years on average after completion of their treatment. Therapeutically
      induced movements and post-therapeutic changes were measured using dental casts,
      and the number of cases which had relapsed was calculated as a percentage of the
      individual measurements. The extent of post-therapeutic changes in patients with
      and without long-term retention was analyzed together with possible correlations
      with retention time and retainer type. Furthermore, the influence of gender,
      Angle classification, treatment-induced changes, initiation, type and duration of
      therapy, and extraction of premolars on the development of relapse was also
      investigated. RESULTS AND CONCLUSIONS: Some degree of relapse was recorded in 13%
      of the measurements on average, even in patients with some form of long-term
      retention. However, it may be possible to reduce the relapse rate by taking
      account of the following criteria: Retention time should be increased in cases of
      short-term therapy, since relapse was found to occur more often on average (19%)
      when the treatment time was less than 3 years than when it was longer than 4
      years (13%). As the highest relapse rate registered was 24% when therapy was
      started between the ages of 9 and 12 years, but was up to 42% in younger and
      older patients, there should be more extensive retention in these latter cases.
      Where there is a risk of relapse in the anterior arch, fixed lingual retainers
      should be given preference over removable ones. This is especially applicable to
      male patients and to non-extraction patients, as relapses in the anterior segment
      occurred more often or were more marked in these cases. The use of removable
      retainers is necessary when the transverse stability of the buccal segment is at
      risk. When only fixed retainers were used in the anterior area, relapses were
      recorded 6-31% more frequently in the interpremolar distance in the maxilla (21%)
      and the mandible (35%), and in the lower intermolar distance (27%). In
      particular, the use of a removable mandibular retainer should not be dispensed
      with after bicuspid extractions, transverse expansion and, in female patients, in
      the lower jaw, as relapse in the buccal segment was more marked or more common in
      such cases. On the basis of our clinical findings and of earlier studies, the
      retention time should be at least 2 years. The retainer type used has been found
      to be just as important as the retention time. If optimum relapse prevention is
      aimed at, fixed maxillary and mandibular retainers in the anterior region should
      be combined with a removable retainer and worn until the patients reach their
      late twenties.

PMID- 11974451
TI  - A prospective randomized study of different retainer types.
AB  - BACKGROUND AND AIM: In recent years, fixed lingual retainers have been gaining
      importance in relapse prevention. The aim of this prospective, randomized study
      was to compare different types of fixed retainers used for stabilization of the
      lower anterior segment with respect to detachment rate, relapse, periodontal and
      oral hygiene problems, as well as subjective patient discomfort. PATIENTS AND
      METHOD: Two types of fixed, customized canine-to-canine retainers (attached to
      six teeth) with wire diameters of 0.0215" and 0.0195" as well as one type of
      prefabricated canine-and-canine retainer (bonded to two teeth) were investigated
      in a total of 103 patients. Some retainers were inserted under dry field
      conditions using a rubber dam, and the others under relatively dry conditions
      using cotton rolls. In addition, two types of composite, Heliosit and Concise,
      were compared. RESULTS: The canine-and-canine retainer displayed an 18%
      detachment rate, a value significantly lower than the 29% determined for the
      0.0195" canine-to-canine retainers. The 0.0215" canine-to-canine retainer had the
      highest detachment rate (53%). The 37% detachment rate with dry field bonding was
      slightly higher than the 32% with relatively dry field bonding. Comparison of the
      composites showed a significantly higher detachment rate for Heliosit (73%) than
      for Concise (27%). Plaque accumulation increased with all retainer types in the
      course of the study, but with no significant inter-group differences. Tooth
      position with canine-to-canine retainers showed a good degree of stability. The
      canine-and-canine retainer induced frequent relapse of incisors not bonded to the
      retainer. In view of their higher rate of subjective discomfort, canine-and
      canine retainers were given a significantly poorer rating than their canine-to
      canine counterparts.

PMID- 11974452
TI  - Influence of masticatory muscle function on transverse skull dimensions in the
      growing rat.
AB  - AIM: The aim of this study was to elucidate the influence of reduced masticatory
      muscle function on the transversal dimensions of the premaxilla, maxilla
      (including the dental arch) and the calvaria in the growing rat. MATERIAL AND
      METHODS: 38 growing male albino rats were used. 14 animals were killed at the
      beginning of the experiment to provide baseline values (Young Group). The
      remaining animals were randomly divided into two equal groups; one received the
      ordinary diet in hard pellet form (Hard Diet Group), and the other a soft diet
      (Soft Diet Group). The experimental period started when the rats were 28 days old
      and had a duration of 28 days. 3D measurements of the dentofacial skeleton were
      performed on dry skulls with a Reflex microscope. RESULTS: No inter-group
      differences were found in mean body weight and overall length of the cranium. The
      dental arch was found to be narrower in the third molar region in the Soft Diet
      Group, possibly due to less growth in the midpalatal suture and/or to reduced
      occlusal loading. This may be due to the first and second molars having been in
      occlusion at the beginning of the experimental period, while the third molars
      were not. Furthermore, the premaxilla and the frontal bones at the most lateral
      part of the temporal crest were narrower in the Soft Diet Group, these regions
      being areas of masticatory muscle attachment.

PMID- 11974453
TI  - Vertical changes in the positions of the cleft segments of patients with
      unilateral cleft lip and palate. Changes from birth to palatoplasty at the age of
      10-14 months.
AB  - PATIENTS AND METHOD: Clinically discernible vertical deviations of the cleft
      segments in nasal direction were registered and visualized using model series of
      16 patients with unilateral cleft lip and palate. All patients were treated
      according to the cleft concept of the University of Leipzig, with labioplasty
      being performed at the age of 4-6 months and palatoplasty at the age of 10-14
      months. All patients had a modified Hotz plate inserted until the palate was
      closed. Casts of a collective of non-cleft infants served as controls. The
      vertical deviations of the segments from the reference plane, defined by us
      through the tuber points and the canine point of the non-cleft side, were
      registered metrically by three-dimensional (3D) measuring of maxillary casts,
      using a reflex microscope. The registered values were represented three
      dimensionally, and the absolute growth was compared with the relative vertical
      changes. RESULTS: The results show that 3D representation with superimposition of
      the individual results offers the clinician clear, continuous monitoring of the
      treatment progress. In comparison with the control group, the cleft patients
      showed significantly greater vertical deviations in nasal direction in the region
      of the incisor and canine points at each observation timepoint. A significant
      reduction in vertical divergences was recorded only in the region of the cleft
      pole point of the larger segment during the study period. The results furthermore
      suggest that investigation of absolute changes in segment positions alone in
      comparison with relative growth changes may lead to misinterpretations.

PMID- 11974454
TI  - Public domain computer-aided surgery (CAS) in orthodontic and maxillofacial
      surgery.
AB  - BACKGROUND: Computer-aided virtual three-dimensional (3D) surgical simulation
      assists the necessary visual understanding of complex pathological situations but
      has so far been dependent on expensive hardware and software. METHOD: For the
      first time a non-commercial, user-orientated application for orthognathic and
      craniofacial surgical simulation has been introduced, based on freeware NIH Image
      1.62 provided by the National Institute of Mental Health (NIMH). Use and
      limitations are demonstrated here by the example of hypertelorism surgery. The
      osteotomy lines and the amount of resection for outward positioning of the orbits
      were determined by the surgeon on a workstation using CT data. Possible movement
      patterns of the osteotomy fragments were rotations, sagittal and transversal
      movements or combinations of these. The program then allows the calculation of
      anatomical distances on the screen in a 1:1 relation. Normative values according
      to age and pathological anatomy determine the degree of displacement. The program
      calculates the new position of the osteotomy fragments and transfers the data of
      the segment movement to the original CT data. RESULTS: 3D visualization of bone
      and soft tissue contours have been produced with an acceptable quality on a
      workstation for the demonstration and visual understanding of the surgical plan.
      Evaluation of a postoperative CT showed that the amount of movement and size of
      bone resection in the simulation was slightly overestimated rather than
      underestimated. This was also dependent on the complexity of the pathological
      anatomy and on how experienced the surgeon was. CONCLUSION: The use of 3D
      simulation programs allows a better understanding of the pathological anatomy in
      all dimensions, and in many cases enables limitations to be recognized in
      advance. The public domain program makes a major contribution to the quality of
      orthognathic and craniofacial surgical planning through cost-free usability, and
      supports continuous development and exchange of experience.

PMID- 11974456
TI  - [Farewell to Professor Christian Herfarth. Two-decade editor of "Der Chirurg"].

PMID- 11974457
TI  - [Surgical endoscopy for staging and the selection of procedure].
AB  - The outcome in the treatment of malignant tumors of the gastrointestinal tract
      can be improved in two ways: by early recognition, and possibly also by
      multimodal treatment concepts. Endoscopic methods are can serve two purposes:
      firstly, the diagnosis and recognition of early and flat lesions; here high
      resolution video-endoscopy, in some cases supplemented by magnification and
      chromo-endoscopy and other extended methods (e.g. autofluorescence), are likely
      to improve the diagnostic accuracy. Another purpose endoscopy and endoscopic
      ultrasound is to select patients suitable for local therapy of early cancers. In
      advanced tumors, endoscopy and especially endosonography are the standard methods
      for predicting the locoregional tumor stage, in order to select patients who may
      benefit from neoadjuvant treatment to select patients for curative treatment or
      palliation. The role of endoscopy and endosonography for the diagnosis and
      treatment of oesophageal, gastric and rectal carcinoma is discussed in the
      following review.

PMID- 11974459
TI  - [Competence -- the way to surgical endoscopy].
AB  - INTRODUCTION: There is a continuing debate about competence for flexible
      endoscopy in regard to surgery. STATEMENTS AND DISCUSSION: The theoretical and
      clinical basis of diagnostic/interventional endoscopy is analyzed; as a result it
      can be demonstrated that surgery offers ideal prerequisites for performing
      endoscopy due to specific training and clinical experience. There are specially
      designed and certified training systems for flexible endoscopy--analogous to
      approved training courses in minimal-invasive surgery. Relevant progress in
      interventional endoscopy in the past and present has been obtained by surgical
      endoscopies. Those involved in interdisciplinary disputes increasingly come to
      the conclusion that cooperation instead of confrontation should be the aim of all
      efforts, thus offering advantages to all participants of such a cooperation.
      CONCLUSIONS: Surgery should preserve and develop further its competence in
      flexible endoscopy.

PMID- 11974458
TI  - [Surgical surveillance and endoscopy. The problem of secondary complication and
      local recurrence].
AB  - Minimal access techniques in surgery are improving. At the same time, the
      significance of interventional flexible endoscopy is increasing. Postoperative
      complications can be treated endoscopically with low rates of morbidity and
      mortality. Anastomotic strictures after resection of the esophagus, colon or
      rectum are mostly treated with success by endoscopy. Reoperations are almost
      never necessary in these cases today. Although the efficient detection of
      locoregional recurrence of gastrointestinal carcinoma is still the subject of
      controversial discussion, in contrast, endoscopic therapy for palliation by
      ablation, dilatation or stenting leads to a clear benefit for many of these
      patients.

PMID- 11974460
TI  - [Differentiated thyroid carcinoma. Surgery and significance of lymph node
      involvement].
AB  - INTRODUCTION: Nodal treatment in papillary (PTC) and in follicular (FTC) thyroid
      carcinoma is still a subject of debate. METHODS: 1974-95 therapeutic
      lymphadenectomy (30/95), 1996-1999 frequent prophylactic lymphadenectomy (32/57;
      P = 0.005) was used for PTC, with therapeutic lymphadenectomy for FTC (15/115).
      131I was used selectively for pN1-tumours. RESULTS: PTC: The incidence of pN0-,
      but not of pN1-status increased significantly (P = 0.03). Nodal recurrence was
      observed in 5/89 (6%) with therapeutic, vs. 1/54 (2%) with prophylactic
      lymphadenectomy (P = NS), i.e. in 1/107 (0.9%) patients without evidence of nodal
      disease, vs. 5/36 (14%) of those with pN1-status (P = 0.0004). Survival at 25
      yrs. in stages TNM I and II was 100%, i.e., independent of N-status. FTC: No
      nodal recurrence was observed. CONCLUSION: Occult untreated nodal disease
      represented no major clinical problem. Selective nodal treatment may offer
      optimal results; meticulous nodal dissection is indicated for N1-tumours.

PMID- 11974461
TI  - [Laparoscopic transhiatal approach to epiphrenic esophageal diverticula].
AB  - INTRODUCTION: The operative treatment for epiphrenic diverticula is usually
      performed via thoracotomy or laparotomy. PATIENTS AND METHODS: Alternatively we
      describe the feasibility of a laparoscopic transhiatal approach in three
      consecutive symptomatic patients with four epiphrenic diverticula. In all cases,
      the diverticula were completely resected laparoscopically in combination with an
      esophagomyotomy and a posterior partial fundoplication. RESULTS: The three
      patients showed uneventful postoperative courses with a speedy recovery and are
      symptom-free after a follow-up of 22-41 months. CONCLUSION: Our results
      demonstrate that laparoscopic transhiatal procedure in patients with symptomatic
      epiphrenic diverticula can be performed safely, effectively, and gently.

PMID- 11974462
TI  - [Therapy of gallbladder carcinoma. Experience of a central hospital].
AB  - INTRODUCTION: There are various options for the treatment of gallbladder
      carcinoma; however, only radical resection offers a chance for prolonged
      survival. METHODS: The aim of this study was to analyze retrospectively patients
      suffering from gallbladder carcinoma in a central hospital in Austria. From 1986
      to 1999, 77 patients were treated in this surgical department. The median age of
      the patients was 71.3 years. RESULTS: In 28 patients the cancer was resected and
      22 persons underwent palliative surgery. An explorative laparotomy was performed
      in 16 patients. Eleven patients had no surgical therapy, 10 persons received
      gemcitabine or a combination chemotherapy regimen consisting of leucoverin, 5
      fluorouracil and mitomycin C. The median survival of patients without
      chemotherapy following radical resection (n = 15) was 10.7 months (one patient
      with metastatic cancer was excluded) and for patients with tumor remaining
      margins (n = 8) 3.2 months (P = 0.023). Without chemotherapy the median patient
      survival following palliative resection (n = 17) and explorative laparotomy (n =
      15) was 1.5 months and 2.1 months. The median survival without surgical therapy
      was 1.6 months. Chemotherapy was administered to four of the resected patients
      (median survival 16.5 months), in five patients following palliative surgery and
      in one patient after explorative laparotomy (median survival 4.3 months) (P =
      0.034). In a multivariate analysis, tumor resection (P = 0.034) and tumor-free
      resection margins (P = 0.025) proved to be the most important determinants for
      patient survival. CONCLUSION: Tumor resection is the most important factor for a
      prolonged patient survival. Following radical resection in an early tumor stage
      and combining this approach with an established chemotherapy, patient survival
      could be increased significantly.

PMID- 11974463
TI  - [Aortoiliac reconstruction after kidney transplantation. Strategies to avoid
      ischemic damage of the transplant].
AB  - INTRODUCTION: The rising life expectancy of patients undergoing kidney
      transplantation and the improvement in the function rate of the allografts have
      led to an increasing number of patients suffering from arteriosclerosis-related
      diseases of the aortoiliac arteries. In these particular cases, an interruption
      of the blood supply of the allograft is always necessary for operative repair of
      the aortic and iliac arteries. This means a high risk of ischemic damage to the
      transplanted kidney. PATIENTS AND METHODS: Between 1987 and 2000, 1,076 kidney
      transplantations were performed in our department. During this time, 14
      reconstructive operations of the aortoiliac arteries were performed in 12
      patients (6 women, 6 men, average age 55.2 (45-71) years). Operations were
      indicated in patients suffering from occlusive disease with imminent extremity or
      allograft loss, and symptomatic or asymptomatic aneurysms with a maximum diameter
      of more than 4 cm. In patients presenting with thoracoabdominal (1) and abdominal
      aortic aneurysms (3), protection of the transplanted kidney was performed by
      axilloiliac or axillofemoral bypass. Hypothermic flush-perfusion of the allograft
      containing PGE1 and heparin was performed in seven of nine operations for
      occlusive disease. RESULTS: None of the patients presented with a permanent
      decrease in kidney function, six patients showed temporary creatinine elevation,
      and in nine patients creatinine levels at discharge were lower than they were
      preoperatively. None of the patients died. CONCLUSION: Reviewing all reported
      methods of allograft protection, we recommend a three-step strategy including
      sequential clamp technique (ischemia < 30 min.), hypothermic flush-perfusion
      (ischemia < or = 60 min.), and temporary axilloiliac/femoral shunt (ischemia > 60
      min), depending on the expected renal ischemia time.

PMID- 11974464
TI  - [Long-term results in the surgical treatment of pilon tibial fractures. A
      retrospective study].
AB  - BACKGROUND: While Pilon fractures of the tibia have been treated for decades by
      primary open reduction and internal fixation by plate osteosynthesis, during the
      last 10 years differential treatment was developed: After primary open reduction
      nowadays patients are treated with (according to type of fracture and tissue
      damage). As well as primary open reduction and internal fixation a two-step
      treatment (primary external fixator and delayed ORIF) or consolidation by
      external fixator combined with minimal invasive osteosynthesis (cannulated screws
      and K-wires) has been implemented. Furthermore, the significance of primary bone
      grafting in comminuted fractures to prevent aseptic pseudarthrosis has been
      acknowledged. METHODS: Of 151 patients with 160 pilon fractures treated from
      January 1979 to May 1995, 107 patients (113 fractures) were evaluated. Only the
      results of C2 and C3 fractures could be compared, as only in these groups were
      all three types of treatment used. RESULTS: Over 75% of the treated fractures
      were closed fractures, most of them being fractures with a soft tissue damage
      grade 2 of the Oestern and Tscherne classification. In the open fractures we
      found mainly grade 3 fractures according to the Gustilo and Anderson
      classification. In 54.9% of all pilon tibial fractures we observed an
      uncomplicated course of healing. Early complications (25.7%) were mainly soft
      tissue infections, whereas we found pseudarthrosis to be the most frequent late
      complication. Highest infection rate (55.5%) was in the two-step treatment group
      (primary external fixator and delayed ORIF) and lowest in the primary internal
      stabilization group, although especially in the C2 and C3 fractures best clinical
      late results were obtained with the two-step procedure. CONCLUSION: The
      complication rate in the treatment of pilon fractures depends mainly on the type
      of fracture, the soft tissue damage and the type of treatment. The results of
      primary ORIF varied. In the case of low-grade soft tissue damage, good to
      excellent results were accomplished. In the case of higher-grade soft tissue
      damage, the problem of soft tissue coverage and reconstruction of the joint
      surface could be solved with good results by the two-step treatment. Herewith it
      is important to use limited open reduction of displaced fragments and fixation by
      cannulated screws and K-wires. We consider ORIF of the fibula necessary as
      stabilization of the second column of the ankle joint.

PMID- 11974465
TI  - [Transhiatal laparoscopic approach in epiphrenic esophageal diverticulum].
AB  - Epiphrenic diverticula are rare. The exact prevalence of this condition is
      unknown because asymptomatic patients are usually not discovered. Symptoms are
      more often the result of an esophageal motility disorder than the diverticulum
      itself and no correlation exists between the size of the diverticulum and the
      severity of symptoms. We present a patient suffering from dysphagia, chest pain,
      food retention and regurgitation because of an epiphrenic diverticulum. The
      current treatment of choice for symptomatic epiphrenic diverticula is
      diverticulectomy via a left thoracic approach. We performed a successful
      abdominal laparoscopic approach.

PMID- 11974466
TI  - [Surveillance of postoperative wound infections: reference data of the Hospital
      Infection Surveillance System (KISS)].
AB  - BACKGROUND: Surgical site infections (SSI), the third-most-frequent nosocomial
      infection, are a problem in all fields of surgery. Assessing the level of one's
      own infection rates is often difficult, since there have been no suitable
      comparative data available in Germany in the past due to the lack of a uniform
      method of determining these rates. METHODS: Based on an American model, the
      Hospital Infection Surveillance System (KISS) has been carrying out a standard
      recording of SSI since 1997 in meanwhile 132 surgical departments of 89
      hospitals. Specially trained hygiene personnel record SSI according to CDC
      definitions in selected indicator operations. RESULTS: Since January 1997, 1,549
      SSI have been recorded in 71,038 operations using 13 different surgical
      techniques. The risk-ratified SSI rates for each of these surgical techniques are
      provided and can serve as orientational data for other departments. CONCLUSION:
      The KISS reference data can help in assessing one's own SSI rates. A prerequisite
      is surveillance according to the KISS protocol.

PMID- 11974467
TI  - [Surgical treatment of intraabdominal hemorrhage in peliosis hepatis].
AB  - INTRODUCTION: Peliosis is an infrequent entity characterized by multiple blood
      filled cavities mostly involving the liver. Peliosis hepatis usually appears as a
      rare autopsy finding in asymptomatic patients or in patients with chronic wasting
      diseases. However, peliosis hepatis may present as hepatic dysfunction or shock
      from hepatic rupture. MATERIAL AND METHODS: In our report we present the case of
      a 33-year-old woman with hepatic peliosis causing a hemoperitoneum resulting from
      liver rupture, which needed immediate surgical treatment. On the basis of
      symptoms and the laboratory parameters the acute abdomen was evaluated by
      abdominal ultrasound and CT scan, both revealing a hemoperitoneum and a lesion in
      the left liver lobe. RESULTS: Embolization was performed by superselective
      catheterization of the left hepatic artery to stop the bleeding. After
      stabilization of the patient, left lobectomy of the liver was performed because
      of the ruptured 15-cm liver tumor. The patient recovered well and was discharged
      without residual complaints. Histopathologic analysis showed focal parenchymal
      peliosis. DISCUSSION: The authors evaluate the effectiveness of the surgical
      strategy in a case of life-threatening focal hepatic disorder. Besides surgery,
      the authors emphasize the importance of invasive radiological interventions in
      these cases.

PMID- 11974468
TI  - [Mesenteric artery occlusion as a rare complication of thromboangiitis
      obliterans].
AB  - Mesenteric artery occlusions are rare complications of Thrombangiitis obliterans
      (Buerger's disease). We report on a 30-year old male with Thrombangiitis
      obliterans and mesenteric occlusion as a complication of this disease. Because of
      unclear abdominal pain, laparoscopy was performed which showed small bowel
      infarction and reduced liver perfusion. After small bowel resection and a second
      examination, ischemia of the intestinum continued. Angiography was performed,
      which showed central occlusion of the celiac trunk and the superior mesenteric
      artery. Relaparotomy with the embolectomy of the superior mesenteric artery,
      venous bypass from the sup.mes.art. to the hepatic arteries and repeated small
      bowel resection was performed. The patient recovered completely and was
      discharged from hospital after 3 weeks. After a further admission to the hospital
      3 weeks later with abdominal pain caused by acute occlusion of the right colonic
      artery and severe ischemia of the right hemicolon, a right hemicolectomy was
      performed. Now, one year after the last hospital admission, the patient shows no
      sign of having any abdominal problems.

PMID- 11974469
TI  - [Postoperative endoscopy for the diagnosis and therapy of complications].
AB  - A variety of endoscopic methods are available as the main tools in the
      diagnostics and therapy of various complications after visceral and thoracic
      surgery. Indications for endoscopic interventions are anastomotic leaks,
      stenoses, Gl-tract bleedings, biliary lesions and functional problems after
      surgical procedures. The most common are fibrin sealing of fistulas, dilatation
      and bougienage, injection therapy for bleeding, bile duct interventions and stent
      implantations. In most cases operative revisions can be avoided by using
      endoscopic methods with an overall good success rate. No disadvantages are
      foreseen following conventional operative interventions if the endoscopic
      treatment is not successful.

PMID- 11974471
TI  - ["Lean" surgery. changes in the surgical "workflow"].

PMID- 11974470
TI  - [Clavicular fractures].

PMID- 11974472
TI  - [Modern operations management in workflow operation. Spectrum of responsibilities
      and challenges for the future].
AB  - The operating unit is one of the cost-intensive facilities in a surgical clinic
      with a pacemaking function for most of the internal procedures. The power of
      performance of the operating unit is based on the co-operation of all disciplines
      and professions involved. The key to management of the operating unit is not only
      to co-ordinate the daily procedures, but also to interact with support personnel.
      To ensure successful OR management, the internal structure of the OR must fit the
      clinical tasks and the available quantity of personnel in each profession must be
      co-ordinated. Sufficient utilization of resources and equipment must be
      guaranteed without cost-intensive over-capacities and patient flow must be
      orientated to OR capacities. The development of such a business structure
      requires the management to clearly define the goal, to know the actual on-site
      data in detail with regard to the idiosyncratic workings of each speciality and
      to clearly assign the competence of each member of the team working in the OR. Co
      ordination of the operating unit is the main task of OR management, which must
      ensure the following: transparent and co-ordinated schedule management in the
      various operative specialities, goal-directed changes of the schedule with
      incorporation of emergencies, as well as effective organization of staff. In
      order to realize these tasks, it is reasonable to implement interdisciplinary
      rules of procedures. In addition, the assignment of a neutral decision-making
      body within the OR and the creation of an information center for all OR
      personnel. The challenge of OR organization in the future is to implement more
      effective documentation systems and active controlling within the OR. One can
      ensure adequate utilization of resources in the OR with prospectively oriented
      planning. Better transparence of operations in the OR contributes to increased
      efficiency. Implementation of quality management is the foundation for a
      successfully operating surgical hospital. Not only the productivity of individual
      members of the staff, but also the precise documentation of the quality of
      results will become important parameters in a successful surgical hospital, whose
      nucleus is the OR.

PMID- 11974473
TI  - [Central patient management in surgery].
AB  - Up to now, in most surgical departments there has been no central patient
      management coordinating the admission, the diagnostic work-up, and the surgical
      procedures of patients with the resources available in the hospital. In future,
      however, it will be essential for surgical departments to establish such a
      central patient management, not only in view of the importance of patient
      oriented medicine but also considering the planned introduction of diagnosis
      related groups. A central patient management will reduce preoperative and overall
      length of stay through adequate organisation and communication structures. In
      addition, a central patient management will make optimal use of the available
      resources in terms of operation rooms and hospital beds. In this article, we will
      present our basic concept of a central patient management in a surgical
      university department.

PMID- 11974474
TI  - [Contribution of anesthesia to workflow operation].
AB  - The changes in our health care system caused by the introduction of DRGs make it
      necessary for us to abandon departmental process structures in favour of total
      hospital orientated process structures. An interdisciplinary approach is crucial
      to enable the most effective use of personnel and material resources. Future
      orientated information technology and organisational structures will enable us to
      process our patients effectively and efficiently from pre-admission to discharge.
      Anaesthesia has to be integrated into a patient management system for in- and out
      patients. The essential matters for consideration are anaesthesia consulting
      hours, the common establishment of process structures for preoperative care,
      operation room management and postoperative patient care. Routine controls and
      analysis of the required teamwork reveal improvement potential and enable us to
      use the necessary control elements effectively.

PMID- 11974475
TI  - [Photodynamic therapy in the gastrointestinal tract. Possibilities and limits].
AB  - BACKGROUND: Photodynamic therapy (PDT) is characterized by the extensive
      selective accumulation of a photoactive agent, the photosensitizer, in malignant
      or precancerous tumour cells. The photoactive compound is activated by light beam
      of a specific wavelength and causes cell death. A significant proportion of
      patients with gastrointestinal malignancies cannot undergo curative treatment, as
      either the cancer is too advanced or the patient's general constitution is too
      poor to allow invasive strategies. In such cases, PDT has already proven to be a
      promising therapeutic modality for selected dysplasias and malignancies in the
      gastrointestinal tract. MATERIAL AND METHODS: A retrospective review of the
      literature was performed in order to determine the experience gained with PDT and
      to assess its clinical value in the curative and palliative management of
      gastrointestinal neoplasms. RESULTS: PDT seems to be an adequate treatment for
      selected forms of early cancer and small lesions of the GI tract or for small
      residual areas after the tumour has been debulked by other techniques (e.g.
      limited surgical resection, thermal ablation). Especially for patients who refuse
      or are ineligible for conventional surgery, PDT offers promising results compared
      to currently accepted clinical approaches. CONCLUSIONS: As a primary or adjuvant
      mode for either curative or palliative treatment of gastrointestinal neoplasms,
      PDT is a potentially effective, minimally invasive therapeutic modality. However,
      further clinical assessment by means of comparative, standardized studies is
      essential to the definition of its role in oncology.

PMID- 11974476
TI  - [Surgical therapy of locally advanced and primary inoperable pancreatic carcinoma
      after neoadjuvant preoperative radiochemotherapy].
AB  - INTRODUCTION: So far, surgery represents the only prospect for cure in patients
      with pancreatic cancer. Most patients, however, present with locally advanced
      pancreatic cancer at primary diagnosis. Recently, novel therapeutic regimens with
      preoperative radiochemotherapy have been developed that may improve long-term
      survival and resectability rates of patients with locally advanced pancreatic
      cancer. METHODS: This feasibility study evaluates the preliminary results of
      neoadjuvant therapy with gemcitabine and 5-fluorouracil (5-FU) or cisplatin.
      Twenty-six patients suffering from locally advanced pancreatic cancer were
      considered for preoperative radiochemotherapy. They received radiation (45 Gy)
      and chemotherapy with simultaneous or sequential gemcitabine and 5-FU (n = 15) or
      gemcitabine and cisplatin (n = 11) administration prior to surgical resection.
      RESULTS: Mean patient age was 62.4 +/- 2.6 years and 62% (n = 16) were male. The
      response rate was 69%, and 11 patients underwent curative surgical resection of
      the pancreatic cancer. Nine Whipple procedures and two complete pancreatectomies
      were carried out. In five patients a total of eight surgical complications were
      observed. Median overall survival was 9.8 months after primary cancer diagnosis
      (mean 12.0 +/- 1.2). During follow-up no local recurrent disease was detected.
      CONCLUSIONS: Our findings lead us to conclude that preoperative chemoradiation
      with 45 Gy, gemcitabine and 5-FU or cisplatin is a powerful therapeutic tool in
      patients with locally advanced non-resectable pancreatic cancer. Major
      resections, including vascular reconstructions, are nonetheless associated with
      increased mortality. Preoperative chemoradiation contributes to improved survival
      in patients with primary non-resectable pancreatic cancer.

PMID- 11974477
TI  - ["Colon-/rectal carcinoma" prospective studies as comprehensive surgical quality
      assurance].
AB  - INTRODUCTION: Currently, only a small percentage of the diagnostic and
      therapeutic data on colonic carcinomas has been confirmed by data obtained in
      randomized controlled studies. For this reason, the results of prospective
      multicentre observational studies are extremely important. METHOD: Within a
      multicentre observational study involving 75 surgical departments carried out
      between 01.01. and 31.12.1999, 3,756 patients with a colorectal carcinoma (2,293
      carcinoma of the colon; 1,463 carcinomas or the rectum) were investigated
      prospectively using a standardised questionnaire. RESULTS: The OP rate was 98.4%,
      the resection rate 92.5% (colon 94.1%, rectum 89.9%). The rate of rectal
      extirpations was relatively high at 30.3%. General postoperative morbidity was
      27.4% (colon 27.0%, rectum 27.9%); the specific postoperative morbidity was 24.6%
      (colon 21.8%, rectum 29.1%). The anastomotic insufficiency rate was 5.2% (colon
      3.7%, rectum 9.5%). The 30-day mortality rate was 4.7%, and the postoperative
      mortality rate 5.7%. CONCLUSIONS: Surgical quality control in the form of
      prospective multicentre observational studies make possible the analysis of the
      therapeutic situation of a surgical disease under quality assurance aspects. At
      the same time, the comprehensive data material available will serve the specific
      planning of prospective randomized studies. With the aid of the present study, a
      basis for a thorough and complete evaluation of colorectal carcinoma has been
      created.

PMID- 11974478
TI  - [T4 rectal carcinoma. Surgical and multimodal therapy].
AB  - BACKGROUND: In locally advanced rectal cancer with infiltration of neighbouring
      organs (uT4), resectability and local control are difficult to achieve. Combined
      preoperative radiochemotherapy may result in increased resectability and reduced
      local recurrence rates. PATIENTS AND METHODS: Thirty-four patients with biopsy
      proven locally advanced rectal cancer were treated by preoperative
      radiochemotherapy. All tumours had been staged as uT4 lesions by endorectal
      ultrasound or computed tomography. Radiotherapy was applied in standard blocks, 5
      x 1.8 Gy up to 45 Gy. Chemotherapy consisted of two cycles of 5-fluorouracil (300
      350 mg/m2/day) and leucovorin (50 mg). In 20 patients, additional thermotherapy
      was carried out using the Sigma 60 applicator BSD 2000 once a week prior to
      radiotherapy. Surgery was performed 4-6 weeks after radiochemotherapy.
      Postoperatively, all patients received four cycles of 5-fluorouracil and
      leucovorin. RESULTS: Treatment-induced toxicity occurred in 26% of the patients
      (WHO grade III (n = 6) and IV (n = 3)). The resectability rate was 76% (26/34
      patients) (R0 resectability n = 21; 62%). The pathological complete response rate
      was 6% (n = 2) and the partial response rate was 47% (n = 16). A local failure
      was observed in six patients after median time of 16 months (range 7-36 months).
      Patients with R0 resection achieved a 5-year disease-free survival rate of 55%
      and a survival rate of 71%. The overall 5-year survival rate for all patients
      with advanced uT4 rectal cancer was 49%. CONCLUSIONS: Our data on preoperative
      combined treatment in locally advanced T4 rectal cancer revealed encouraging
      downstaging, local control, and survival rates.

PMID- 11974479
TI  - [Polypropylene synthetic mesh modifies growth of human cells in vitro. An
      experimental study].
AB  - INTRODUCTION: The aim of our study was to investigate the influence of
      polypropylene meshes on the proliferation and apoptosis of human cell cultures in
      vitro. METHODS: Human fibroblasts and HeLa cells were incubated in different
      densities (10(4), 3.10(4), 10(5) cells/well) together with polypropylene meshes
      (Prolene, 2 x 2 cm) in six-well culture dishes over a 48-h period. Cells without
      meshes served as controls. Cells were spun on slides and stained with the
      monoclonal antibody MIB-1. To calculate the proliferation indices, stained nuclei
      were counted. Apoptotic indices were determined by flow cytometric analysis,
      using FITC-conjugated Annexin-V and propidiumjodide for staining. RESULTS:
      Fibroblasts showed only a slight reduction of the proliferation index (PI) from
      64% (controls) to 60% (meshes). Increasing cell density leads to a decrease in
      the PI of both groups. The PI of HeLa cells was similar in mesh groups and
      controls and independent of cell density. The apoptotic index (AI) of fibroblasts
      was significantly higher in the mesh group (3.7%) in comparison with the controls
      (1.9%). The same was observed for HeLa cells (AI mesh group: 4.5%, AI controls:
      1.2%). Furthermore, an increase of AI was found with increasing cell density in
      both cell lines. CONCLUSION: Whereas meshes did not influence the proliferation
      of the cell lines examined, they seem to have a marked influence on apoptosis, as
      a significant increase of AI was observed in the mesh group in contrast to
      controls.

PMID- 11974480
TI  - [Significance of prospective multicenter observational studies for gaining
      knowledge in surgery].
AB  - The meta-analysis of randomised controlled studies (RCS) achieves the highest
      degree of reliability. Although the status of prospective multicenter clinical
      trials (PMS) is the subject of controversial discussion, recent publications
      suggest that these two forms of analysis reveal comparable results. On the other
      hand, particularly in the operative part of medicine, the problem of recruitment
      and performing of controlled studies for the more rapid evaluation of new
      surgical procedures becomes more evident. We followed these two aspects by using
      a separate analysis of data and biostatistical models. In the evaluation of
      single aspects, under no circumstances can non-controlled clinical trials replace
      randomised clinical studies in surgery. Only the use of a variety of forms of
      analysis in clinical research will lead to the desired scientific findings.

PMID- 11974481
TI  - [The surgeon as a cost factor. Cost analysis exemplified by surgical treatment of
      rectal carcinoma].
AB  - INTRODUCTION: Besides quality, costs play an increasingly important role. For
      rectal carcinoma, the cost of the surgical treatment of the disease (including
      after-care) was analysed under variable clinical conditions. METHODS: Eleven
      patients (eight men, three women, median age 57 years) with curative resection of
      rectal carcinoma between 1991 and 1995 were selected: Five patients with an
      uneventful course remaining recurrence-free, three patients who developed an
      anastomotic leakage and three patients with locoregional recurrence during their
      further course. In three patients, adjuvant radiochemotherapy was performed after
      resection of the primary tumor. For each patient, costs from the first
      postoperative day until the end of an assumed after-care of 5 years' duration
      were analysed. RESULTS: Costs for the postoperative period of the primary
      treatment ranged between 3.162 DM and 149.988 DM, in case of development of an
      anastomotic leakage between 14.699 DM and 149.988 DM. Adjuvant radiochemotherapy
      increased costs by 12.265 DM up to 23.259 DM, locoregional recurrence caused
      additional costs between 9.461 DM and 27.301 DM. Cost group analysis showed the
      costs for nursing care to be the highest (30% of total costs), followed by the
      expense for drugs and medication. Total costs of treatment ranged from 7.361 DM
      to 160.833 DM. CONCLUSIONS: Costs as well as the patient's prognosis depend to a
      great extent on the quality of the procedure and consequently on the individual
      operating surgeon. A complicated course is associated with a considerable
      increase in costs. A complete cost analysis of rectal carcinoma has to include
      the cost of a potential locoregional recurrence which would lead to the
      additional prolonged after-care for these patients.

PMID- 11974482
TI  - [Influence of the space layout of a surgical department on use efficiency].
AB  - There is a growing gap between the rapidly increasing diagnostic and therapeutic
      opportunities and the patient demands on one side and the continuously declining
      hospital budgets on the other side. This gap forces hospitals to search for
      rationalization potentials and ways to increase their efficiency. It is well
      known that the operating theatre unit is one of the most important internal cost
      factors. Many reorganization projects therefore focus on operating theatres. In
      Germany, several alternative operating room layouts have been developed in order
      to reduce running und building costs and to reach a high degree of flexibility in
      their everyday use by means of an improved design. This article analyses and
      compares the classic operating room and four alternative layouts intended to make
      them suitable for reaching the promised objectives and, especially, achieving an
      economically run business management. Furthermore, preferred layouts for certain
      types of operations are recommended.

PMID- 11974483
TI  - [Survey of therapy of deep venous thrombosis among members of the German Society
      of Vascular Surgery].
AB  - INTRODUCTION: In the literature of the past 15 years, deep venous thrombectomy
      has been rarely described. The only indications reported for thrombectomy seem to
      be recurrent pulmonary embolisation and phlegmasia coerulea dolens. Many
      contraindications and severe complications are making decisions concerning
      thrombolysis very difficult. At present, anticoagulation therapy is preferred
      over fibrinolysis. There is no conclusive concept for the standardization of
      treatment for deep venous thrombosis. As a first step towards achieving this, it
      was necessary to know what therapy is performed in hospitals throughout Germany.
      METHODS: In 1999, we sent letters of enquiry to the members of the "Deutsche
      Gesellschaft fur Gefasschirurgie". We wrote to 341 members (hospitals), and the
      information gained by means of a questionnaire was analysed and evaluated.
      RESULTS: We received answers from 39.9% (n = 136) of the members. In all, 69% of
      the hospitals had an independent vascular department. In 1999, 6,718 patients
      underwent treatment for deep venous thrombosis, on average, 51 patients per
      hospital. Overall, 7,665 therapies were performed in one year (15.9%
      thrombectomy, 18.6% fibrinolysis, and 65.5% only anticoagulation). Only 23.5% of
      the hospitals had their own data about the outcome of their patients. The patency
      rate was 71.8% for thrombectomy and 48.9% for fibrinolysis. A severe
      postthrombotic syndrome was seen in 6.2% after thrombectomy, in 8.1% after
      fibrinolysis, and in 10.4% after singular anticoagulation. CONCLUSION: At
      present, there is still no standardized concept for the treatment of patients
      with deep venous thrombosis. It seems that there are better results for some
      indications with thrombectomy than with other methods. For the establishment of a
      concept of treatment, a prospective randomised study is necessary.

PMID- 11974484
TI  - [What is the cost of vascular operations? A prospective cost analysis of
      conventional and combined endovascular interventions].
AB  - Current and future legislation demand improved efficiency in the medical
      services. The aim of this study was to analyse the costs of vascular surgery in
      order to reveal potential ways of reducing expense. Taking into account the
      staff, equipment and operating theatre supplies, we analyzed 58 elective
      operations comprising 47 conventional and 11 combined endovascular procedures.
      The mean overall costs calculated for the different operations were: 5.269 DM for
      a transfemoral embolectomy (n = 3), 8.504 DM for a patchplasik of the profunda
      arteria (n = 8), 10.265 DM for a femoro-popliteal bypass with a prosthesis (n =
      6)--13.180 DM with a vein (n = 2), 9.864 DM for conventional iliac artery
      reconstruction (n = 7)--iliac endovascular combined procedure (n = 4) 14.494 DM,
      14.951 DM for a Y-prosthesis in case of stenosis (n = 3)--13.288 DM in case of
      infrarenal aortic aneurysm (IAA, n = 4), 11.954 DM for a tube prosthesis in case
      of IAA (n = 3), 23.571 DMY-stent prothesis for IAA (n = 5), 19.914 DM stent for a
      thoracic aneurysm (n = 2), 7.153 DM a carotid thrombendarterectomy (n = 6), 5.503
      DM for varicosis surgery (n = 5). Because of the high cost of materials, the
      total outlay for combined endovascular procedures appeared to be high when
      compared to conventional vascular surgery. Substantial savings concerning the
      operation may only be achieved if facility structure and qualification of staff
      meets the particular requirements.

PMID- 11974485
TI  - [Craniocerebral trauma].

PMID- 11974486
TI  - [Health economics--more important today than ever?].

PMID- 11974487
TI  - [Scientifically based patient education exemplified by patients with primary
      systemic vasculitis. The vasculitis patient education program--development,
      contents and initial results of evaluation].
AB  - Referring to the literature, it is known that structured standardized patient
      education represents an effective additional treatment in patients with chronic
      diseases. Most programs are based on cognitive behavioral interventions. Within
      the last few years, an interdisciplinary approach for providing information on
      disease, therapies, side effects, coping strategies, nutrition and physiotherapy
      has been developed for patients with primary systemic vasculitides (PSV) in the
      vasculitis center of the Medical University of Lubeck/Bad Bramstedt. The contents
      of the seminars were revised and condensed into five modules. New slides and
      handouts for patients were developed. To evaluate the new form of the program, a
      documentation system consisting of patient and physician-administered
      questionnaires assessing socioeconomic, knowledge and disease-related outcome
      parameters was designed. Patients are trained in closed groups (n = 10-15) and
      asked to complete questionnaires at baseline, 4 weeks and 6 months after
      training. First results show statistically significant improvement of knowledge
      and health-related quality of life.

PMID- 11974489
TI  - [Research in patient care in the rheumatology specialty network--what is the
      benefit for improving patient care?].
AB  - One of the areas of research in the Rheumatology Competence Network deals with
      health services research. It evaluates the structures and outcomes of
      rheumatological care. The paper presents selected results from the projects in
      the field of health services research. Data for rheumatoid arthritis are
      presented according to the criteria for the inclusion of diseases in new health
      care programs ("Disease Management"). The national database of the German
      Collaborative Arthritis Centers and cohort studies show the high individual and
      economic burden of disease in rheumatoid arthritis. Treatment by rheumatologists
      and non-rheumatologists differs greatly and leads to different outcomes. There is
      great potential for improvement. Data on practice variation within the
      rheumatologic subspecialty are used for quality management. The involvement of
      rheumatology into new concepts of care offers the chance to show the
      effectiveness of rheumatologic care and to enhance existing forms of cooperation.

PMID- 11974488
TI  - [Health economics research in the area of chronic polyarthritis].
AB  - Costs of illness are of major economic relevance in rheumatoid arthritis (RA) as
      in other chronic diseases. Overall costs of 15,000 Euro/year: 10,000 Euro
      indirect costs, and 5000 Euro direct costs are estimated, respectively. A further
      detailed analysis of direct costs underlines that inpatient care (50%) is the
      most prominent cost driver. Medication costs are also evaluated in detail since
      they are expected to gain importance with the introduction of the more expensive
      biologicals. While annual costs for regular disease modifying drugs (DMARDs) vary
      from 160 to 5000 Euro per patient, costs for the new biologicals amount up to
      20,000 Euro (100-125% of the current estimated overall costs). For a comparison
      of different therapeutic strategies, costs are related to effectiveness in cost
      effectiveness analyses. Based on present clinical trials, the ratios of
      medication costs and response according to the ACR 20-criteria of various DMARDs
      and biologicals are compared. The most cost-effective medication is sulfasalzine,
      followed by methotrexate, and leflunomide. Combining etanercept and methotrexate
      is preferable to methotrexate monotherapy and the combination of infliximab and
      methotrexate. This review shows that important economic issues in RA have already
      been addressed by applying cost-of-illness analyses and cost-effectiveness
      analyses. However, the knowledge about cost-effective therapeutic options is
      still scarce. Thus, primary data will have to be obtained using standardized
      approaches. These economic findings can be taken into account in the development
      of disease-management recommendations for RA-therapy.

PMID- 11974490
TI  - [Epidemiology and patient management in the area of spondyloarthritis].
AB  - Within the group of inflammatory rheumatic diseases, spondyloarthropathy is the
      most common diagnosis after rheumatoid arthritis. Its prevalence was long
      underestimated. Ankylosing spondylitis (AS) and undifferentiated
      spondyloathropathy (uSpA) are the most common subgroups in western countries.
      There are still difficulties in diagnosis especially of the early forms of the
      spondyloarthropathies. Data of socioeconomics and therapeutic options are
      limited. In more recent times, researchers have started to investigate the burden
      of disease and the socioeconomic aspects. Better diagnostic options are available
      and promising new therapeutic agents, especially TNF-alpha blocking agents, have
      been investigated. However, further studies are urgently needed for this
      underestimated group of diseases and are currently being performed inside the
      German rheumatology network.

PMID- 11974491
TI  - [Basic principles in rheumatologic patient education. Theoretical principles and
      didactic aspects].
AB  - Nowadays, the handling of a chronic disease is seen as a process, influenced by a
      variety of factors. Case studies, taken from health behavior, help to illustrate
      the conduct of patients suffering from chronic diseases and develop strategies of
      how to increase a patient's skills in coping with his illness. The concept of
      self-efficacy beliefs is of great importance and will be discussed in detail. In
      addition, possible effects of patient education in the comprehensive treatment of
      rheumatic diseases will be presented. In teaching methods, equal emphasis is
      placed on the transmission of information as on the development of practical know
      how. They are on a par with emotional support, motivation, assistance in
      accepting the disease and coping with fear. The special methods and media
      required will be discussed, along with the framework for training methods and
      qualification required of the staff in charge of training.

PMID- 11974492
TI  - [Analysis of immunoglobulins and complement factors in synovial fluid and serum
      in rheumatoid arthritis, seronegative spondyloarthropathies and osteoarthritis:
      pathophysiology and retrospective analysis of clinical value].
AB  - Synovial fluid (SF) analysis was a mandatory investigation in rheumatological
      practice. In recent time, synovial fluid analysis lost importance predominantly
      due to unclear defined guidelines for the practical use. OBJECTIVE: To evaluate
      the clinical value of the determination of the complement components C'3c and C'4
      and immunoglobulines IgG, IgA and IgM synovial fluid concentrations with regard
      to pathophysiology and currently used RA and SpA classification criteria.
      METHODS: Synovial fluid samples were obtained from 22 patients fulfilling ACR
      criteria for rheumatoid arthritis (RA), and 18 patients suffering from
      seronegative spondyloarthropathy (SpA) according to the ESSG criteria. Sixteen
      osteoarthritis (OA) SF samples were used as controls. IgG, IgA, IgM, C'3c and C'4
      in SF and sera were determined by nephelometry. Comparison of the diseases, and
      linear as well as stepwise logistic regression analyses were performed in order
      to determine the interrelation of the determined parameters and a ranking of
      their diagnostic value for the identification of RA or SpA synovial fluids.
      RESULTS: SF-IgA, SF-IgG and SF-IgM concentrations were closely correlated with
      their corresponding serum levels (p < 0.01), while SF-C'3c and SF-C'4 depended on
      articular factors (p < 0.01). Determination of SF-C'3c (accuracy = 80.4%,
      improved chi 2 = 22.02, p < 0.001) and SF-C'4 (accuracy = 75.0%, improved chi 2 =
      21.81, p < 0.001) both provided a good predictive value for the diagnosis of SpA
      when exceeding the cut off level of about 40 mg/dl (C'3c) or 15 mg/dl (C'4),
      respectively. Calculation of the C'-SF/S ratios did not provide an additional
      diagnostic benefit. SF-IgG, IgA and IgM as well as the calculated SF/S ratios
      were within the same range in RA and SpA fluids. CONCLUSIONS: SF concentration of
      complement components primarily depends on local articular factors. Significant
      differences of SF complement concentrations in established RA and SpA give reason
      for prospective analysis of these parameters in early undifferentiated
      oligoarthritis and evaluation in large studies, e.g. when re-evaluating the
      preliminary criteria for spondyloarthropathy.

PMID- 11974493
TI  - [Subungual chondroma, a case report].
AB  - Subungual chondroma is a rare occurrence of periosteal chondroma, which mainly
      affects short tubular bones of the hands and feet. Transformation towards
      malignancy has been described in a small number of cases; however histologic
      diagnosis can prove to be difficult, especially with regard to well
      differentiated chondrosarcoma. We report the case of a 14 year old girl with a
      one year history of subungual chondroma of the fourth toe with good clinical
      response to surgical removal.

PMID- 11974494
TI  - [Parallel occurrence of Paget disease and Bechterew disease].

PMID- 11974495
TI  - [Repeat antibiotic therapy is ineffective in patients with persistent symptoms of
      Lyme borreliosis].

PMID- 11974496
TI  - [The promising student Pierre Marie (1853-1940)].

PMID- 11974497
TI  - [Another's suffering. How can we better understand how to help him?].

PMID- 11974498
TI  - [Final report of the Professional Community of Regional Cooperative Rheumatology
      Centers of Germany concerning model measures of the federal ministry for public
      health].

PMID- 11974499
TI  - [The situation of dermatopathology in Europe. Tasks, priorities and
      premonitions].

PMID- 11974500
TI  - [Histological diagnosis of inflammatory skin diseases. Use of a simple algorithm
      and modern diagnostic methods].
AB  - The histological diagnosis of inflammatory skin diseases on a day-to-day routine
      basis poses the difficult task to characterise a dynamic clinical process by
      histomorphological analysis of one single lesion. Very complex algorithms which
      are meant to lead to the correct diagnosis are difficult to use. To facilitate
      the process and reduce the number of algorithms the following method is proposed:
      1. Histological examination under low power Definition of lesions altered by
      scratching 2. Localisation of the significant pathological alterations as
      follows: Changes in epidermis and dermis Blister formation Changes in
      dermis/subcutis without characteristic changes in the epidermis Changes mainly in
      the subcutis 3. Closer examination using a simple algorithm and planning of
      further investigations following defined criteria: In the case of changes in
      epidermis and dermis definition of spongiotic, psoriasiform or lichenoid
      dermatitis (Abb. 1). In the case of blister formation definition of the blister
      following the given algorithm (Abb. 1). In the case of changes in dermis/subcutis
      without characteristic changes in the epidermis after exclusion of vasculitis and
      lymphoma definition of the main pattern as lymphocytic, neutrophilic,
      eosinophilic, lymphoplasmocytic or granulomatous and following the given
      algorithm (Abb. 2). In the case of changes mainly in the subcutis after exclusion
      of vasculitis and lymphoma definition of the main pattern of panniculitis as
      septal or/and lobular (Abb. 2). Exclusion of PAS positive microorganisms and
      checking if the general pattern fits into infectious correlation. Use of
      clinicopathological correlation.

PMID- 11974501
TI  - [Ten clues to the histopathologic diagnosis of infectious skin diseases].
AB  - Specific diagnoses of infectious skin diseases can be established in
      dermatopathology by several methods: by algorithms based on pattern analysis, by
      differential diagnosis of clinicopathologically similar disorders, by attention
      to pitfalls, by exceptions to the rules and finally, very elegantly by clues. Ten
      clues to specific diagnoses of infectious skin diseases which are of importance
      in routine practice are presented. Clue 1: Features of an angiocentric
      angiodestructive lymphoma in the centre of a wedge-shaped necrotic insect bite
      reaction are a clue to a bite by a spider. Clue 2: Parakeratosis with spiky
      imprints on the surface above features of an insect bite reaction are a clue to
      scabies. Clue 3: A faintly eosinophilic section of a skin specimen with prominent
      fibrin thrombi and extravasated erythrocytes are a clue to a septic fungal
      vasculitis. Clue 4: Infectious agents in association with otherwise typical
      features of leukocytoclastic vasculitis are a clue to septic vasculitis. Clue 5:
      Steel-grey nuclei with marginated nucleoplasm of keratinocytes are a clue to the
      diagnosis of early infection by herpes virus. Clue 6: Owleye-like cells are a
      clue to infection by cytomegalovirus. Clue 7: Detection of Entamoeba histolytica
      in perianal and perineal ulcers are a clue to amebiasis. Clue 8: Round-oval to
      rectangular spaces within the stratum spinosum of the epidermis are a clue to
      larva migrans. Clue 9: Macrophages and plasma cells in association with otherwise
      typical features of pityriasis lichenoides are a clue to secondary syphilis. Clue
      10: A lichenoid infiltrate of lymphocytes and plasma cells are a clue to
      acrodermatitis chronica atrophicans.

PMID- 11974502
TI  - [Basic principles of skin biopsy].
AB  - Skin biopsies are easy to perform, can be done under direct visual control, allow
      precise clinico-pathological correlation, and, accordingly, the significance of
      skin biopsies is very high. This review discusses the basic principles of the
      interpretation of skin biopsies and alerts to problems that may result from the
      absence of representative changes of a pathological process in the tissue
      sections, poor processing of tissue, incorrect assessment of histopathology
      findings, and shortcomings in the clinico-histopathological correlation.

PMID- 11974503
TI  - [Reaction patterns to cutaneous particulate and ornamental tattoos].
AB  - Particulate matter incorporated into the skin of former miners was compared to
      ornamental tattoos with regard to composition and cutaneous reaction pattern. The
      specimens were examined histologically and immunohistochemically followed by
      scanning electron microscopy and element analysis. In the skin biopsies
      containing dirt particles, silicon and aluminium were regularly found and the
      particles were positively birefringent under the light microscope. Even years
      after the initial foreign particle incorporation strong reactions against quartz
      containing substances deposited perivascularly and perifollicularly continued to
      take place. Reactions ranged from strong macrophage activation to pre
      granulomatous changes. Anthracotic pigment was demonstrated in all layers of the
      dermis depending on the degree of traumatic insult and the colour pigments of the
      ornamental tattoos showed a variable spectra of elements depending on the type of
      dye used. Fibrous reactions were only discrete, however, strong macrophage
      activation and sometimes capillary proliferation as well as non-specific
      lymphocytic infiltration could still be confirmed even decades after the initial
      incorporation. In conclusion, the cutaneous incorporation of ornamental tattoo
      dyes and accidental dirt particles is not an inert process. Even years later, non
      specific macrophage activation as well as discrete inflammatory changes in an
      attempt to degrade the foreign material can still be documented. A clear
      correlation between subcutaneous incorporated quartz particles and progressive
      systemic sclerosis was not found in this study.

PMID- 11974504
TI  - [Invisible dermatosis].
AB  - The microscopically "invisible dermatoses" comprise a heterogeneous plethora of
      skin disorders which are characterized by a stunning discrepancy between the
      classical clinical findings and very discrete histological alterations suggesting
      "normal skin." Methods and strategies for the correct histopathological diagnosis
      of seemingly normal skin are discussed.

PMID- 11974505
TI  - [Keratoacanthoma. A variant of highly differentiated squamous cell carcinoma and
      its differential diagnosis].
AB  - Keratoacanthomas represent epithelial tumors which are characterized by a keratin
      filled crater, rapid growth in the proliferation stage, and the potential for
      spontaneous regression. Histologically, keratoacanthomas display distinct
      features which must be differentiated from squamous cell carcinomas in the
      proliferation stage and fully developed tumors and in the regression stage the
      differential diagnosis of verruca vulgaris must also be considered.

PMID- 11974506
TI  - [Benign adnexal skin tumors].
AB  - Epithelial tumors of the cutaneous adnexae are considered to originate from three
      different structures, i.e., hair follicles, eccrine/apocrine sweat glands, and
      sebaceous glands. Although this derivation provides a practical basis for
      classification, some tumors may exhibit a mixed differentiation and thus should
      be categorized according to the prevailing phenotype. The overwhelming majority
      of hair follicle tumors are benign but the main diagnostic differential for
      malignant tumors is basal cell carcinoma. Despite a broad histological spectrum,
      benign tumors of sweat glands are readily recognized on the grounds of a well
      characterized morphology. However, it may be difficult to rule out malignancy as
      each benign entity has a malignant counterpart. True sebaceous neoplasms are rare
      when hyperplasia and hamartoma are disregarded and in extraocular locations most
      of them are benign.

PMID- 11974507
TI  - [Eccrine sweat gland carcinoma of the skin].
AB  - Sweat gland carcinomas represent a group of morphological heterogeneous tumors
      with clear differences regarding clinical course and prognosis. The most relevant
      and accepted entities are described clinically and histopathologically with
      special reference to the differentiation from benign adnexal tumors. Carcinomas
      arising from preexisting benign adnexal tumors such as spiradenocarcinoma,
      cylindrocarcinoma, malignant mixed tumors of the skin are easily recognized. To
      establish the diagnosis of microcystic adnexal carcinoma or aggressive digital
      papillary adenocarcinoma can be more difficult, because these carcinomas do not
      show cytological criteria for malignancy and may therefore resemble benign
      adnexal tumors especially in small specimens.

PMID- 11974508
TI  - [Melanocyte tumors. Classical and new diagnostic possibilities].
AB  - Melanocytic tumors are one of the major problems in diagnostic dermatopathology
      as they comprise benign nevi, malignant melanomas and borderline cases. Apart
      from a proportion of congenital lesions, most benign nevi are acquired tumors
      that arise during early adulthood and eventually may undergo regressive change.
      Histologically, they present as so-called common nevi, so-called dysplastic nevi,
      Spitz's nevi, blue nevi and their variants, and combined nevi. In typical cases,
      the distinction from a malignant melanoma is not difficult. However, benign
      simulators of malignancy exist as much as deceptively bland appearing melanomas
      and in some cases the diagnosis remains dubious despite careful weighting of
      criteria. Indeed, morphological features may not always suffice to disclose the
      nature of a melanocytic tumor. Ancillary techniques including
      immunohistochemistry and measurement of telomerase activity may be of assistance
      in this respect. One should nevertheless be aware that the biological behavior of
      certain borderline cases cannot be predicted with certainty.

PMID- 11974509
TI  - [Inflammatory skin diseases. An assortment of clinically relevant disease
      conditions].
AB  - In the following a short overview on inflammatory dermatoses which are frequently
      diagnosed in clinical dermatology is presented. These include allergic contact
      dermatitis, dyshidrotic dermatitis, nummular dermatitis, seborrheic dermatitis,
      atopic dermatitis, lichen planus and psoriasis. Special emphasis is laid on the
      evolutionary stages in the development of lesions, clinically as well as
      histologically. The abovementioned dermatoses have a special pathological
      reaction pattern in common: the epidermis, papillary dermis and superficial
      capillary-venular plexus react together in these conditions and have therefore
      been termed the superficial cutaneous reactive unit.

PMID- 11974510
TI  - [Cutaneous mesenchymal neoplasms versus mesenchymal neoplasms of subcutaneous and
      deep soft tissue. Similarities and differences].
AB  - As in subcutaneous and deep soft tissues, cutaneous mesenchymal neoplasms are
      also relatively rare and characterized by a clinicopathological heterogeneity.
      There are striking differences in regard to the occurrence of different lines of
      differentiation of mesenchymal neoplasms in superficial and deep locations, and
      some distinct entities arise exclusively in the dermis. Superficially located
      mesenchymal neoplasms are characterized by a number of specific morphological
      features in comparison to deeper located lesions. Clinically important, dermal
      sarcomas of some lines of differentiation are associated with a favorable
      clinical prognosis, independent of the histological grading, which is important
      to know for the correct treatment of patients. In the following review
      similarities and distinguishing clinicopathological features of superficially and
      deeply located mesenchymal tumors are discussed.

PMID- 11974511
TI  - [Normal values of the Giessen Test for over 60-year-old probands].
AB  - A representative sample of N = 507 elderly over 60 years of age (mean age: 69.46
      years; 42.6% male; 57.4% female) was assessed in 1999 by means of the Giessen
      test (GT) in 1999. Means and standard deviations are given for sub-groups
      according to gender, age and place of residence (East vs. West Germany) for items
      and scales, and percentile ranks are given for the GT scales. Furthermore,
      reliability of the GT scales for the elderly is reported (Cronbach's alpha; split
      half-reliability). Reliability is satisfactory except for the scales "Control"
      and "Dominance". Further, the correlations between the GT scales and the scales
      of the NEO-FFI are given. The correlations of the GT scales "Social response",
      "Openness", and "Social potency" with the scale "Extraversion" of the NEO-FFI
      indicate a clear interpersonal component of the GT. A depressive mood as measured
      by the Giessen test corresponds positively with neuroticism as measured by the
      NEO-FFI.

PMID- 11974512
TI  - [Age dependence of laboratory parameters in a health study--attempt at
      calculating a laboratory index for assessing biological aging].
AB  - The laboratory analyses of 404 participants of the health study GUNDULA, 201 men
      and 203 women between 30 and 80 years old, were performed to evaluate the
      variables for the determination of biological age. From the more than 70
      laboratory variables resulting from clinical-chemical and hematologic tests and
      from urinalysis, less than 40 are significantly age-dependent. About half of
      these variables were examined by regression analysis to evaluate whether they are
      useful for the estimation of biological age by a laboratory index. Considerable
      sex differences were observed. The laboratory indexes for the participants
      altogether (resulting from 13 parameters) and separated for women (10 parameters)
      and men (8 parameters) show more variations than the biological age estimated by
      non-invasive parameters. In men only, there exists a significant but inverse
      correlation between laboratory index and relative aging rate, the difference
      between biological and chronological age. The results of some striking variables
      (e.g. dehydroepiandrosterone sulfate and others) and the results of an
      explorative factor analysis with regard to possible interconnections between
      variables and chronological age will be discussed.

PMID- 11974513
TI  - [Adaptation of a dementia test for use in visually handicapped persons
      exemplified by SIDAM (Structured Interview for the Diagnosis of Alzheimer
      disease, Multi-Infarct Dementia and Dementias of other Etiology)].
AB  - In epidemiological field studies on the prevalence and incidence of dementia, the
      problem of cognitive testing of visually impaired individuals is rarely
      discussed. In the Leipzig Longitudinal Study of the Aged (LEILA 75+) a version of
      the SIDAM (SIDAM-Structured Interview for the Diagnosis of dementia of the
      Alzheimer type, Multi-infarct dementia and dementias of other etiology) for the
      visually impaired was employed from which all items requiring image processing
      had been omitted (SIDAM-blind). In order to be able to interpret the test
      results, the final scores for the full SIDAM were estimated by linear
      transformation of the scores in the blind-version. The method of linear
      transformation is based on certain theoretical assumptions which are examined in
      this paper. Linear transformation of scores has proved to be a valid procedure
      only for individuals with high cognitive performances. Thus, an evaluation of
      estimated scores based on the norms for the original SIDAM has limitations.
      Consequently, age-specific norms for the SIDAM-blind are presented. Sensitivities
      and specificities for different cut-off points used to discriminate between
      demented and non-demented vision-impaired individuals are given.

PMID- 11974514
TI  - [Effect of daily living-related cognitive training on attention and memory
      performance of persons with dementia].
AB  - There are few results of controlled studies about psychological interventions,
      i.e. training of cognitive functions in dementing illnesses. Most frequently very
      specific memory strategies are trained, (the effects of) which cannot be
      generalized to activities of daily living. Thus, a memory training program was
      developed considering the different cognitive abilities of the participants and
      which was meant to be generalized to daily tasks. Short-term and long-term memory
      were trained as well as activities of daily living in 12 lessons for a period of
      6 weeks. We can show significant improvements of attention and memory performance
      in our experimental group in comparison to the control group.

PMID- 11974515
TI  - [Effects of social support on well-being of demented nursing home residents. The
      Kaferberg Visitation Study].
AB  - BACKGROUND: Relatives and caregivers of patients with dementia are often insecure
      about the impact of their efforts. This study examines whether and to what extent
      social support in the form of regular visits is increasing the well-being of
      demented aged. PROCEDURE: A field experiment with slightly to seriously demented
      institutionalized aged persons (MMS 5-25) was carried out to assess the effect of
      increased social support upon their well-being. Voluntary helpers, who were
      willing to visit their patients on a regular basis, were recruited by appeals at
      the senior university and by advertisements. The volunteers were trained to deal
      with the demented and were looked after regularly. The test subjects were
      randomly assigned to one of two test groups. The first group was visited
      regularly for ten weeks, whereas the second group served as a control group. The
      participants of the experimental group received a visiting card with a photo of
      the volunteer and the next appointment date to remember their visitors and to
      increase the effect of predictability. RESULTS: The effect of visits on the well
      being of the institutionalized aged persons was significantly positive (F(1,39) =
      11.16, p < 0.002). The psychological, physiological and social well-being of the
      participants was improved. Additionally, visits moderated the pain resulting from
      physical illness and seemed to decrease the effects of mental decline on their
      performance. Furthermore, it was most impressive to find that the demented aged
      really took notice of the visits and seemed to remember them in one way or an
      other. The study pointed out that demented aged persons are still very sensitive
      in an emotional respect and that they are still able to give astonishing good and
      differentiated information about their feelings even in an advanced state of
      dementia. Even the volunteers gained from their visits, which was shown by their
      higher well-being after their visits.

PMID- 11974516
TI  - [Hamburg Declaration].

PMID- 11974517
TI  - [Low molecular weight heparins after orthopedic and traumatologic operations in
      geriatrics].
AB  - Deep vein thrombosis and pulmonary embolism are common complications after
      orthopedic and trauma surgery. To prevent these complications, the use of low
      molecular-weight heparins (LMWH) as prophylaxis is well proved and accepted. We
      reviewed 203 patients undergoing geriatric rehabilitation in our hospital after
      orthopedic and trauma surgery. Despite a prophylaxis with LMWH, 23 (11.3%) of
      these patients were diagnosed with having a clinically apparent and
      sonographically confirmed thromboembolic event. The average age of all patients
      was 81.8 years; the time between surgical or orthopedic intervention and
      thrombembolic event was on average 29.4 days. Using evidence-based medicine, a
      search of the literature showed 34 clinical trials concerning the prophylaxis of
      thrombembolic events with LMWH after orthopedic or trauma surgery. All studies
      have been reviewed for age of patients and for duration of prophylaxis with LMWH.
      The average age of all patients involved is 65.8 years. There are only 4 trials
      with an average age of 75 years or more, with a total number of less than 250
      patients. The mean duration of prophylaxis with LMWH is 12.5 days. Only 6 trials
      concern thromboprophylaxis given longer than 3 weeks after surgical intervention.
      We conclude that there are no clear data about safety, efficiency and optimal
      duration of prophylaxis with LMWH in geriatric patients undergoing orthopedic or
      trauma surgery.

PMID- 11974518
TI  - [Subjective need for help and objectified geriatric assess. Comparison of the
      Halberstadter Gerontologic Study and the Augsburger Senior Study].
AB  - The Halberstadt Geriatric Study and the Augsburg Senior Citizens Study contain
      common elements of geriatric assessment (self-assessment of functional
      dependence, objective evaluation of the functional status). In our cross
      sectional investigation, the objective was to examine associations between
      functional dependence and functional tests and to investigate whether association
      patterns differed between the surveyed groups. The prospective Halberstadt study
      began in the German Democratic Republic in 1983 within the framework of a
      vocational examination before employees entered retirement. In 1995 the study was
      reactivated; 367 survivors answered a postal questionnaire of which 167 persons
      took part in a test battery including performance and psychometric tests. The 214
      Augsburg test persons had already taken part in the MONICA survey (monitoring of
      trends and determinants of cardiovascular disease). In 1997 they were assessed in
      a follow-up study, the aim being to determine the functional status of an elderly
      cohort through interviews and functional tests. In both studies functional
      dependence was defined by the (I)ADL concept [(instrumental) activities of daily
      living]. The participants' functional status was determined with the help of
      performance tests such as foot tapping and cognitive tests such as the Mini
      Mental State Examination. Additionally, medical diagnoses and the use of medical
      facilities were investigated. The presence of functional dependence was
      consistently and predominantly significantly associated with the functional
      status assessed by performance tests. These results were largely confirmed by a
      logistic regression model. Our results show that even in populations with a
      different socialization, performance tests are stable indicators of functional
      dependence and should therefore be incorporated in geriatric assessment programs.
      The introduction of a standardized assessment program with subsequent
      intervention measures could lead to a delay of functional dependence and need of
      care and reduce costs in the health care system.

PMID- 11974519
TI  - Healthcare organizations and the Internet: impact on federal tax exemption.
AB  - Tax-exempt healthcare organizations have turned to the Internet as a powerful
      tool in communicating with the public, medical staff, and patients. Activities as
      diverse as providing links to the Web sites of other organizations, selling goods
      and services, soliciting contributions, and hosting forums on the Internet raise
      unresolved questions concerning the impact of Internet use on such organizations'
      tax-exempt status. The Internal Revenue Service has provided no guidance to date
      regarding the manner in which a nonprofit organizations' use of the Internet may
      affect its tax-exempt status or subject it to federal income tax on some sources
      of funds. This article suggests analytical approaches for applying existing law
      in the Internet context and identifies areas that are ripe for additional
      guidance.

PMID- 11974520
TI  - The liability of medical directors for utilization review decisions.
AB  - Managed Care Organizations (MCOs) have turned to numerous cost-containment
      measures to combat rising healthcare costs. One of the most common is the use of
      utilization review to ascertain whether a recommended mode of treatment is
      "medically necessary." When the medical director of an MCO determines that care
      recommended by a patient's treating physician is not medically necessary and not
      eligible for coverage (and, as a result, potentially unattainable due to cost),
      the stage is set for litigation. In such situations, medical directors may become
      potentially liable for disciplinary action by their state medical licensing board
      as well as lawsuits for malpractice or negligence. However, plaintiffs wishing to
      recover damages for improper determinations of this nature or state boards trying
      to discipline these physicians, face the hurdles of the preemptive force of
      ERISA, and state doctrines to the effect that corporations (and, derivatively,
      their medical directors) cannot practice medicine and therefore cannot be liable
      for malpractice. Conflicting decisions and opinions make it impossible at the
      present time to have a settled expectation regarding the potential liability of
      medical directors in this context, although the law appears to be moving toward
      the treatment of utilization review as medical decisionmaking; therefore, it
      appears likely that the activities of medical directors increasingly will face
      state oversight--including the imposition of common law liability in appropriate
      situations.

PMID- 11974521
TI  - What you don't know can hurt you: why managed care organizations have a legal
      duty to disclose the use of financial incentives to limit medical care.
AB  - This article, winner of the 2000-2001 American Health Lawyers' Student Writing
      Competition, examines the conflicting policy goals at the heart of managed care-
      particularly in the use of financial incentives for physicians who limit their
      use of referrals and expensive diagnostic tests. While conceding the legality of
      such incentives, the author contends that Managed Care Organizations (MCOs) have
      a legal duty to disclose their existence to beneficiaries. After analyzing the
      basis for imposing a duty to disclose, the author proceeds to examine such issues
      as the proper timing, level, and extent of disclosure.

PMID- 11974522
TI  - HIPAA privacy: the compliance challenges ahead.
AB  - This Article reviews the HIPAA Privacy Standards' impact on healthcare
      organizations. It discusses whether a healthcare organization is a "Covered
      Entity" under the regulations, what information the Privacy Standards protect,
      what restrictions the regulations place on the use and disclosure of protected
      health information, what individual rights the Privacy Standards create, and what
      agreements they require between healthcare organizations and their business
      associates. The author provides relatively extensive guidance to organizations
      that are embarking upon their voyage of compliance with these broadly applicable
      regulations, but notes that the full extent of necessary compliance remains
      unclear, pending DHHS issuance of the next iteration of the rulemaking in this
      area. The Article was finalized in January 2002, before HHS issued any
      modifications to the Privacy Standards.

PMID- 11974523
TI  - Distance health services under the general agreement on trade in services.
AB  - This Article discusses the state of distance health with respect to the General
      Agreement on Trade in Services (GATS). After examining the various aspects of
      telemedicine and its place in international trade, the author looks at the
      structure and functioning of GATS and how telemedicine is regulated under this
      agreement. The author argues that the potential for telemedicine under this
      agreement has yet to be fulfilled and suggests a number of ways to realize its
      potential. Ultimately, however, the author concludes that the single most
      important international trade objective for the United States healthcare industry
      should be to get its own house in order with respect to cross-border provision of
      health services. From an international trade perspective, the problem of non
      uniform state licensure requirements within the United States makes it very
      difficult for the United States to negotiate market access commitments for
      distance health services with other countries. Therefore, it is not realistic to
      expect significant progress in the liberalization of distance health services
      until the United States has in place a reasonably uniform domestic system of
      licensure and regulation for telemedicine practitioners.

PMID- 11974524
TI  - [Genetic composition of the Chilean population. Analysis of mitochondrial DNA
      polymorphism].
AB  - BACKGROUND: The analysis of mitochondrial DNA restriction site polymorphisms
      assigns most Latin American aborgines to four haplogroups. These are
      characterized by determined polymorphic restriction sites and a deletion of 9
      base pairs in the intergenic region V. AIM: To study the distribution of
      mitochondrial DNA haplogroups in Chilean aboriginal groups, as well as in the
      mixed population of Santiago. MATERIAL AND METHODS: One hundred twenty Aymara
      subjects and 23 Atacameno subjects from the Northern part of Chile and 162
      randomly chosen subjects residing in Santiago were studied. DNA was extracted
      from peripheral lymphocytes. Mitochondrial DNA was amplified by means of
      polymerase chain reaction. RESULTS: The frequency of haplogroup B decreases from
      north to south. Aymaras in the north have the highest frequency (64%) and it is
      absent among the Yamanas (previously studied) in the extreme South. Haplogroups C
      and D show an inverse tendency. It is noteworthy that 84% of mitochondrial
      haplogroups of the mixed population of Santiago are of Amerindian origin whereas
      the Y-chromosomes are mainly European. CONCLUSIONS: The peculiar distribution of
      haplotypes indicate that the population of Santiago is the result of an
      asymmetric mating system in which the females ancestors were mainly Amerindian
      and the male ancestors mainly European.

PMID- 11974525
TI  - [A 36 years experience with implantable pacemakers. A historical analysis].
AB  - BACKGROUND: The implantation of pacemakers improves cardiac function and quality
      of life, in particular with dual chamber DDD and DDDR modes. AIM: To evaluate our
      clinical experience and results on pacemaker implantation, from 1963 to 1998.
      MATERIAL AND METHODS: Computerized data collected from 2,445 consecutive paced
      patients was reviewed. A total of 3,554 operative procedures were performed,
      including 412 procedures for complications and 697 pacemaker replacement. Patient
      survival was determined from clinical records, inquiry to pacemaker manufacturers
      and death certificates from Servicio de Registro Civil e Identificacion de Chile
      (Chilean Civil and Identification Registry). RESULTS: Use of dual chamber (DDD
      and DDDR) pacemakers increased progressively up to 74% from 1988 to 1998.
      Complication rate was 42% in the 1963-1976 study period, it decreased to 10.6% in
      the 1977-1987 study period, and to 5.6% by 1988-1998. Only two patients died
      during surgery in the study period (0.08%). In the 1977-1987 period, pacemakers
      lasted 10.6 years. Survival rates were 52% at ten years, 33% at 15 years, and 21%
      at 20 years, with a median survival of 11.7 years, and 7.24 years in patients
      over 80 years old. CONCLUSIONS: Transvenous permanent pacing can be accomplished
      today with a low complication rate, mainly due to better technology and surgical
      procedures.

PMID- 11974527
TI  - [Effects of Helicobacter pylori eradication on gastroesophageal reflux in
      patients with duodenal ulcer].
AB  - BACKGROUND: Helicobacter pylori infection is not a risk factor for
      gastroesophageal reflux disease and it could even be a protector factor. AIM: To
      study the relationship between H pylori eradication and gastroesophageal reflux
      symptoms in patients with duodenal ulcer. PATIENTS AND METHODS: One hundred
      eleven patients with duodenal ulcer and treated for H pylori infection were
      studied. In 96 patients, H pylori was successfully eradicated and were evaluated
      every four months with endoscopy, during the first year. Thereafter, an annual
      clinical assessment was performed and endoscopy was repeated only if clinically
      indicated. RESULTS: Patient were followed for a mean of 41 months (range 4 months
      to 6 years). Twelve patients (10.8%) had esophagitis at recruitment and in nine,
      H pylori was eradicated. The frequency of gastroesophageal reflux symptoms or
      esophagitis in this group was similar to the rest of patients. During the first
      year, the frequency of reflux symptoms ranged from 9 to 19%. The frequency of
      esophagitis persisted at about 10%, although 81% of patients with esophagitis did
      not have it on recruitment. After the first year, the frequency of reflux
      symptoms declined significantly to about 8%. CONCLUSIONS: In these patients with
      duodenal ulcer, gastroesophageal reflux disease had a variable evolution after H
      pylori eradication.

PMID- 11974526
TI  - [Helicobacter pylori genotypes in non atrophic gastritis are different of the
      found in peptic ulcer, premalignant lesions and gastric cancer in Colombia].
AB  - BACKGROUND: Helicobacter pylori is recognized as an etiologic agent of several
      gastric diseases. Bacterial genotypes have been related to clinical outcome in
      several populations. AIM: To compare cagA, vacA and iceA genotypes of Colombian
      isolates from patients with several gastrointestinal diseases, including gastric
      cancer. MATERIAL AND METHODS: We used polymerase chain reactions to amplify vacA,
      cagA and iceA genes of 137 H pylori isolates coming from 26 patients with gastric
      cancer (GC), 34 with peptic ulcer (PU), 19 with intestinal metaplasia (IM), 23
      with atrophic gastritis (AG) and 35 with non atrophic gastritis (NAG). RESULTS:
      vacA s1-m1, cagA+, iceA+ were the most frequently found genotypes. vacA s1 and m1
      subtypes were found in 92 (67%) and 82 (60%) cases respectively. Sixty three
      percent were cagA+ and 85% were iceA+. There was a lower prevalence of s1 allele
      in cases of NAG (43%), compared with GC, PU and IM (81%, 77% and 81% prevalence,
      respectively, p < 0.01). Isolates from NAG also showed a low frequency of vacA m1
      subtype (40%) compared with GC or IM (81% and 84% respectively, p < 0.01). The
      prevalence of cagA+ strains was significantly higher in GC patients (80%) than in
      NAG patients (51.4%, p < 0.01). No differences in the frequency of vacA s1a, s1b
      and iceA subtypes, were observed. CONCLUSIONS: A lower frequency of cytotoxic H
      pylori genotypes such as cagA and vacA s1m1 and a higher frequency of non
      cytotoxic genotypes, was observed in patients with NAG, when compared to patients
      with GC or PU. These results suggest that even in Colombia, vacA and cagA could
      be used as markers of increased virulence.

PMID- 11974528
TI  - [Prevalence of symptoms associated with blood pressure in normal and hypertensive
      population].
AB  - BACKGROUND: High blood pressure should be symptomless. However, popular knowledge
      attributes some symptoms such as headache, epistaxis or dizziness to high blood
      pressure. AIM: To compare the prevalence of headache, epistaxis, subconjunctival
      hemorrhages and dizziness in people with normal or high blood pressure. SUBJECTS
      AND METHODS: A representative sample of an urban population in Chile was studied.
      Each subject with high blood pressure was paired with a non-related individual of
      the same sex and age. These subjects were interrogated about the presence of
      symptoms. RESULTS: One thousand forty eight subjects with high blood pressure
      (481 male) and 1052 individuals with normal pressure (483 male), were studied. In
      subjects with high or normal blood pressure, the prevalence of headache was 22
      and 21.8% respectively, epistaxis was 11.6 and 11% respectively, dizziness was
      7.4 and 7.6% respectively, tinnitus was 9.1 and 9.4% respectively and
      subconjunctival hemorrhage was 2.9 and 3.1% respectively (p = NS). CONCLUSIONS:
      No differences in the prevalence of symptoms, popularly attributed to
      hypertension, were observed between subjects with normal or high blood pressure.

PMID- 11974529
TI  - [Anti thyroglobulin antibodies in the follow up of patients with differentiated
      thyroid cancer: residual or relapsing disease markers?].
AB  - BACKGROUND: Anti thyroglobulin antibodies are present in 25% of patients treated
      for a differentiated thyroid cancer, invalidating thyroglobulin determination.
      Those patients subjected to total thyroidectomy and free of disease, should
      reduce the production of these antibodies, due to the lack of antigenic stimulus.
      Therefore, anti thyroglobulin antibodies could be useful to detect early
      relapses. AIM: To assess the relationship between anti thyroglobulin antibodies
      and the evolution of the disease in patients treated for thyroid cancer. MATERIAL
      AND METHODS: Retrospective analysis of 26 patients treated for thyroid cancer
      with positive anti thyroglobulin antibodies, followed for three years. These were
      divided in those with or without lymphocytic thyroiditis (19 and 7 respectively).
      RESULTS: At the first year of follow up, anti thyroglobulin antibody
      concentration was 401 +/- 94.9 UI/ml (x +/- sem) in patients with thyroiditis and
      38.9 +/- 8.9 UI/ml in those without thyroiditis (p < 0.005). During the three
      years of follow up, no differences in anti thyroglobulin antibodies were observed
      between patients with or without tumor relapse. CONCLUSIONS: Concentration of
      anti thyroglobulin antibodies was higher in patients with thyroiditis and did not
      differentiate patients with tumor relapse.

PMID- 11974530
TI  - [Intrarenal arterial doppler ultrasonography in cirrhotic patients with ascites,
      with and without hepatorenal syndrome].
AB  - BACKGROUND: The pathophysiological hallmark of the hepatorenal syndrome (HRS) is
      renal vasoconstriction. Doppler ultrasonography can be used to assess the
      vascular resistance in small renal intraparenchymal vessels through analysis of
      the Doppler waveform by a parameter termed Resistive Index (RI). We postulated
      that the RI could be important for the diagnosis and prognosis of HRS. AIMS: To
      assess the RI in cirrhotic patients with ascites, with and without HRS. PATIENTS
      AND METHODS: We studied 48 cirrhotics with ascites, of whom 12 were with and 36
      without HRS and other 23 were normal subjects. We measured the intrarenal
      arterial RI (Resistive index = Peak systolic velocity - Minimum diastolic
      velocity/Peak systolic velocity) with color Doppler ultrasonography after
      visualization of interlobular or arcuate arteries. It was considered abnormal
      when higher than 0.70. RESULTS: The RI values, mean and SD) were: normal
      subjects: 0.58 +/- 0.05, cirrhotics with ascites: 0.65 +/- 0.05 and cirrhotics
      with ascites and HRS: 0.78 +/- 0.11. Patients with HRS had significantly higher
      values than those without HRS (p < 0.001). The Relative Risk of developing the
      HRS in patients with a RI > or = 0.70 were 3.32 (CI 95% = 1.79-6.2) CONCLUSIONS:
      The RI was useful in patients with cirrhosis and ascites for the prognosis of HRS
      and could suggest diagnosis of HRS with values of 0.78 or higher, if other
      clinical conditions that produce renal vasoconstriction are excluded.

PMID- 11974531
TI  - [Health care resource allocation in Chile. Ethical considerations in decision
      making].
AB  - BACKGROUND: The inclusion of ethical aspects in the world health care reform is
      currently being discussed. AIM: To analyze the ethical component of health care
      decision making in Chile. MATERIAL AND METHODS: A qualitative analysis of
      interviews with 4 health service directors, 4 public hospital directors and 1 sub
      director. Inquiries to 16 public hospital ethics committees, about importance of
      ethical components in decision making, role of ethics committees in financial
      issues and the feasibility of incorporation explicit ethical considerations in
      decision making. RESULTS: There is an absence of explicit ethical criteria in
      decision making. There is little participation of directors in these issues and
      lack of information. Although ethical aspects are considered relevant, they are
      not taken into account. Ethics committees are mostly dedicated to evaluate
      research protocols. The community is not mentioned as a relevant actor in
      decision making about resource allocation. CONCLUSIONS: Health service directors
      and all health care personnel should be trained in bioethics. These aspects
      should be incorporated to their daily work.

PMID- 11974533
TI  - [Pulmonary hypertension and pregnancy].
AB  - A 36 year old woman, with an 18 year history of syncope, became pregnant shortly
      after a cardiac catheterization demonstrated a high pulmonary arterial pressure
      and resistance and a low cardiac output. During pregnancy she remained stable at
      NYHA FC III, on nifedipine, apresoline, isosorbide, aspirin and bed rest. At 28
      weeks, catheterization showed a decreased pulmonary pressure and an increased
      cardiac output. At 38 weeks, she was submitted to an elective caesarean section,
      and delivered a healthy newborn of 2820 g. After 5 months, her catheterization
      showed a pulmonary artery pressure similar to the pre-pregnancy study. Her
      condition deteriorated, leading to death 10 months later. Urinary 6-keto
      PGF1[symbol: see text], nitrates/nitrites, kallikrein and angiotensin-(1-7) were
      increased from 13 to 33 weeks, to drop in week 35 of pregnancy. The safe maternal
      and fetal outcome, and the intragestational hemodynamic improvement are
      attributed to a close multidisciplinary surveillance, and to the effects of the
      endogenous vasodilators of pregnancy on the reversible component of the pulmonary
      hypertension. Reports in the literature show a decrease in maternal mortality
      rate, from 56% for the period previous to 1963, to 34 and 30% for those spanning
      between 1978-1996 y 1997-2001 respectively.

PMID- 11974532
TI  - [Study of neurological diseases prevalence in Aratoca, a rural area of eastern
      Colombia].
AB  - BACKGROUND: Current health statistics on the prevalence of neurological diseases,
      in Colombia, are still lacking. AIM: To determine the prevalence of migraine,
      cerebrovascular disease, movement disorders, peripheral neuropathies, mental
      retardation and developmental disorders, epilepsy, dementia and sequels of
      cranial trauma in a rural population of Colombia. MATERIALS AND METHODS: We
      evaluated 544 subjects in Aratoca, a rural place of Santander, placed at 400
      kilometers from Bogota. The world health organization (WHO) protocol for
      neuroepidemiological studies modified by our group, a survey to determine sequels
      of cranial trauma and the mini mental state examination were used as instruments.
      People 12 years-old or more and suspected to have a neurological disease was
      evaluated by adult neurologists and those less than 12 years-old were evaluated
      by a neuropediatrician. RESULTS: 223 out of 544 subjects surveyed were evaluated
      by the clinicians of which 135 had a neurological disorder. The prevalence of
      neurological diseases, per thousand inhabitants were as follows: migraine 189.3;
      epilepsy 33; febrile seizures 25.6; peripheral neuropathy 22.1; mental
      retardation 18.4; developmental and language disorders 11; dementia 10.5;
      cerebrovascular disease 4.7; and movement disorders 3.7. CONCLUSIONS: These
      results will allow to define appropriate control measures, as well as to prevent
      and treat these prevalent neurological disorders in rural places of Colombia as
      Aratoca and the like.

PMID- 11974534
TI  - [Eosinophilic fasciitis: report of 3 cases].
AB  - Eosinophilic fasciitis (EF) is a scleroderma-like disease of unknown etiology
      characterized by cutaneous swelling and induration that affects predominantly the
      extremities, elevated immune globulins, and peripheral eosinophilia. We report
      three patients with clinical, laboratory and pathologic characteristics of EF.
      The main symptoms were cutaneous and included "peau d' orange", groove signs and
      induration of the affected extremities. Two patients had skin changes after
      exercising and one had a hypothyroidism. None had extra-cutaneous manifestations.
      All patients had peripheral eosinophilia. Pathologic findings were thickening and
      inflammation of the fascia and normal epidermis. Only one patient was treated
      with prednisone 30 mg daily and showed only moderate improvement. There is no
      follow up information about the other two cases. EF is a rare disorder classified
      at times as scleroderma variants. However, its clinical picture, capillary
      microscopy findings, pathology and prognosis differentiate it from systemic
      sclerosis.

PMID- 11974536
TI  - [The patient with refractory functional disorders of the gastrointestinal tract].
AB  - A group of patients with functional disorders of the gastrointestinal tract,
      manifest symptoms that are chronic, severe and invalidating. Their refractoriness
      to different treatments is a great challenge for physicians. They normally have a
      severe psychological and social dysfunction and an abnormal behavior towards
      their disease. All these factors lead these patients to perpetuate their illness
      condition. On the other hand, physicians usually have a negative reaction to
      their demands, leading to a non-satisfactory patient-physician relationship and
      to the failure of the healing process. Training in the systemic, biopsychosocial
      model of diseases and in interpersonal communication skills is required for an
      adequate management of these patients.

PMID- 11974535
TI  - [Macroglossia and occult amyloidosis].
AB  - Amyloidosis is a rare disease characterized by the pathological deposit of
      extracellular proteins in organs or tissues. We report a 78 years old female with
      a history of euthyroid goiter and carpal syndrome, that presented complaining of
      weight loss and the sensation of a big and rough tongue. On physical examination,
      macroglossia and white nodules of 1.5 cm diameter in the mucosa of the mouth,
      were observed. The pathological examination of these nodules disclosed amyloid
      infiltration. A bone marrow biopsy showed plasma cell infiltration. The patient
      was treated with melphalan and prednisone, but she deteriorated progressively and
      died 14 months after the diagnosis.

PMID- 11974537
TI  - [Medical audit: a modern undervalued management tool].
AB  - Medical audit is defined as the critical and periodical assessment of the quality
      of medical care, through the revision on medical records and hospital statistics.
      This review defines the work of the medical auditor and shows the fields of
      action of medical audit, emphasizing its importance and usefulness as a
      management tool. The authors propose that every hospital should create an audit
      system, should provide the necessary tools to carry out medical audits and should
      form an audit committee.

PMID- 11974538
TI  - [Management of early gastric neoplasm].

PMID- 11974539
TI  - [The 100th birthday of Karl Schuchardt].

PMID- 11974540
TI  - [Patient satisfaction with the outcome of surgical orthodontic intervention and
      effect of esthetic and functional criteria].
AB  - BACKGROUND: The aim of the study was to analyze the influence of possible
      temporary or permanent disorders of sensation on the degree of the patient's
      satisfaction following an orthognathic operation. PATIENTS AND METHODS: After an
      average of 47 months (range: 9-141), a follow-up examination was performed in 78
      women (64.5%) and 43 men (35.5%) with an average age of 24.3 years (range: 19-40)
      at the time of operation. In 67 cases there had been a sagittal division of the
      mandible, in 11 cases a Le Fort I osteotomy, in 26 cases a bimaxillary osteotomy,
      in 4 cases an isolated genioplasty, and in 13 cases a segmental osteotomy in the
      upper or the lower jaw. In the peripheral area supplied by the nerves V2 and V3
      sensation was examined by the two-point discrimination test and the result
      related to the patients' satisfaction using the chi-square test. RESULTS AND
      DISCUSSION: The following qualities of sensation were recorded: anesthetic
      (2.7%), hypesthetic (16.6%), paresthetic (8.3%), and normesthetic (72.4%). The
      patients' satisfaction was rated as very satisfied in 51.3%, as satisfactory in
      44.8%, and in 3.9% the patients' expectations had not been fulfilled; 75%
      regarded their outward appearance as markedly improved and a good 50% of the
      patients noted improved mastication. Therefore, three-fourths of all the patients
      would even be willing to be operated on again. Two-dimensional analysis, however,
      demonstrated only a weakly significant positive relationship between patient
      satisfaction and the preserved, or restored, sensation in the trigeminal region.

PMID- 11974541
TI  - [Experimental and histomorphologic studies of healing processes of anastomoses of
      the carotid artery in the Wistar rat animal model with immunohistochemical
      imaging of collagen IV].
AB  - INTRODUCTION: The main risk in free flap tissue transfer is posed by the
      microvascular anastomosis. The dangers confronting the anastomosis are
      thrombosis, aneurysm, and vascular insufficiency. Collagen IV is associated with
      the basement membrane complex. It plays an essential role in vascular tissue
      organization and supports mechanical properties of vessels. We used a long-term
      animal experiment to gain a new understanding of histomorphological apposition of
      anastomosis and distribution of collagen IV. METHODS: Seventy Wistar rats, seven
      groups of ten animals each, were operated. A 4-mm long segment of the common
      carotid artery was isolated and reinserted. After a varying length of time
      (between directly after the operation and 6 months later), the common carotid
      arteries including bifurcation were isolated after cardiovascular perfusion.
      Carotid arteries were embedded, and cross-sections were stained with hematoxylin
      and eosin, Verhoeff's tissue elastin stain, and immunohistochemical anti-collagen
      IV antibody. By using the above-described technique in each section four
      anastomoses were examined. The histomorphology and intensity of the anti-collagen
      IV stainings were evaluated. RESULTS: Compression, shift, and dehiscence as forms
      of vessel apposition were often seen. We observed an overexpression of collagen
      IV in the media in cases of compression and shift. The grade of expression of
      collagen IV in the anastomosis depends on the extent of the injury. CONCLUSIONS:
      A well-performed microvascular anastomosis is clinically important not only for
      the acute phase after the operation, but also for the long-term course. The
      application of antibodies to identify the collagen IV distribution is valuable
      for studying vascular healing. Further applications could be used in follow-up
      studies of vascular prostheses.

PMID- 11974543
TI  - [Risk and prevention of lesions of the lingual nerve in wisdom tooth osteotomy.
      Analysis of the literature and faculty opinion in maxillofacial surgery in German
      speaking countries].
AB  - BACKGROUND: Disturbance of lingual nerve function is one of the relevant
      complications after surgical removal of lower third molars. In the literature,
      however, protective measures against this complication are not unanimously
      recommended. In order to find out the current opinion in terms of the state of
      the art in this field, a questionnaire was sent to the heads of 39 University
      Departments for Oral and Maxillofacial Surgery in Germany, Austria, and
      Switzerland. All of them responded. TECHNICAL FINDINGS: In 54% of the
      departments, a periosteal elevator or similar instrument is recommended for the
      protection of the lingual nerve in every instance, whereas in 8% of the
      departments this is not recommended. In the remaining departments, the decision
      about protective measures is made according to the individual anatomical
      situation. STATISTICS AND DISCUSSION: The literature review revealed insufficient
      data quality for a sound data-based decision on whether and when to use an
      instrument to protect the lingual nerve. In any case, the statistical risk of a
      temporary disturbance of the lingual nerve seems to be higher with use of the
      lingual split (0.5%-19.8%) than with the lateral osteomtomy technique (0%-1.9%).
      In contrast to widespread opinion, even in anatomically difficult cases, there
      seems to be no statistical advantage of the standardized use of a protective
      instrument either in respect to temporary or permanent nerve damage. Yet, a
      slight increase of temporary lesions seems to be documented when the instrument
      is used. According to the current literature data, the subperiosteal insertion of
      an instrument to protect the lingual nerve cannot be considered an essential
      standard procedure in each case.

PMID- 11974542
TI  - [Malignant facial tumors. Ambulatory therapy and new methods of cancer
      prevention].
AB  - BACKGROUND: The growth rate of malignant facial skin tumors is one of the highest
      of all malignancies. The predominantly older patients mostly wish outpatient
      treatment. The aim of the study was to describe the strategy and results of
      outpatient tumor surgery. Based on two representative surveys, another objective
      was to establish whether it is useful to involve dentists in early cancer
      diagnosis. MATERIAL AND METHODS: The retrospective case analysis comprised 77
      patients (average age 67.8 years) in a private maxillofacial practice with a
      total of 100 malignant skin tumors. All patients were operated by the same
      surgeon. A frozen section analysis was carried out in 75 patients. Two surveys
      including 2500 participants each were conducted to determine the frequency of
      consultations with dermatologists for skin cancer checkup and the incidence of
      doctor-patient contacts among different specialists in the past 12 months.
      RESULTS: A total of 96% of the patients could be operated "in sano" in a one
      stage procedure. Of these patients, 50% needed further intraoperative resections
      based on the frozen section analysis. Of the excisional defects, 71% could be
      closed by local flaps and 24% by skin grafting. Follow-up examinations after a
      mean of 34.6 months revealed one local recurrence. The surveys showed that only
      17.4% of the interviewees contacted the general practitioner at least once every
      2 years while 61.1% of those surveyed never had their skin examined. In the last
      12 months, general practitioners were the most frequently consulted doctors
      (67.6% of the interviewees), followed by dentists in second place (44.1%). Other
      specialists were less frequently consulted. CONCLUSIONS: One-stage outpatient
      treatment of malignant facial skin tumors in combination with frozen section
      analysis is a reliable and practicable method. After attending medical
      continuation courses, dentists should play a more active role in the prevention
      of skin cancer because of their frequent doctor-patient contacts.

PMID- 11974544
TI  - [Foreign body in paranasal sinuses].
AB  - AIMS: All cases of the last 5 years requiring foreign bodies to be removed from
      the paranasal sinuses were investigated as to causes, special aspects in
      diagnostics and therapy, occurrence of pathologic germs and possible sequels.
      PATIENTS: 68 cases were evaluated: 43 patients were male, 25 female. Average age
      was 29 years in males and 37 years in females. RESULTS: In our patients foreign
      bodies in the paranasal sinuses were in more than 60% the result of medical or
      dental procedures followed by industrial accidents (25%). The maxillary sinus was
      affected in 75%, the frontal sinus in about 18%. Involvement of the ethmoid or
      sphenoid sinus was rare. The spectrum of pathologic microbes was dominated by
      mixed infections, the share of actinomyces and aspergillus was unexpected high.
      Most important acute complications were bleeding, compression of the optic nerve
      and liquorrhoe. Late complications consisted mainly of pain--often associated
      with disturbances of sensibility- and infections. CONCLUSIONS: A smear should be
      taken whenever the foreign body remained in the sinus for more than 4 days.
      Foreign bodies jammed in the posterior wall of the sinus require a sufficiently
      open view since the risk of heavy bleeding is especially high.

PMID- 11974545
TI  - [Development of speech and facial skull growth after primary velopharyngoplasty
      in lip-jaw-palate clefts].
AB  - BACKGROUND: A two-armed, prospective, randomized study was performed to evaluate
      the influence of primary velopharyngoplasty on speech and facial growth in
      patients with cleft lip and palate. PATIENTS AND METHODS: Forty-two patients born
      between 1978 and 1982 were included. All patients were treated with an intravelar
      veloplasty, and 21 patients simultaneously with a velopharyngoplasty according to
      Sanvenero-Rosselli. The patients were examined at the age of 5, 10, 15, and 18
      years according to the recommendations of the research group of the German
      Association of Craniomaxillofacial Surgery for minimal documentation. RESULTS:
      Patients treated with primary velopharyngoplasty showed a higher deficit in
      transversal growth of the maxilla of 0.6 mm in the molar region in adolescence in
      comparison to the control group. The sagittal growth of the maxilla was reduced
      at 2.6 degrees in the SNA angle. A statistically significant decrease in growth
      of the maxilla caused by primary velopharyngoplasty was not detectable (p >
      0.05). The incidence of rhinophonia and dyslalia did not differ significantly.
      Primary velopharyngoplasty did not lead to speech improvement either in childhood
      or in adolescence. CONCLUSION: With regard to a potential decrease in growth of
      the maxilla and the disadvantages of a hindered nasal respiration, a primary
      velopharyngoplasty therefore does not seem to be indicated.

PMID- 11974546
TI  - [Possibilities and limitations in evaluating treatment concepts in lip-jaw-palate
      clefts].
AB  - BACKGROUND: Recently, government and medical practitioners have shown
      considerable interest in the discipline of evidence-based medicine. LITERATURE
      RESEARCH AND RESULTS: In this study, we investigated the literature concerning
      treatment concepts in cleft surgery according to criteria of evidence-based
      medicine. Over the last decade 996 articles on cleft patients were published, 181
      of which were studies evaluating the clinical outcome of distinct treatment
      options. Only 57 studies proved to be classifiable due to a well-described study
      protocol. One treatment study of cleft patients reached the strength of evidence
      grade I and strength of recommendation grade A, whereas all other studies had a
      lower evidence rating. DISCUSSION: The reasons behind these findings seem to be
      due to problems faced by the specialty of this disease.

PMID- 11974547
TI  - Bone grafting to the jaws with special reference to reconstructive preprosthetic
      surgery. A historical review.
AB  - The first report on the transfer of fresh bone was in 1668 when van Meekeren
      described how a Russian surgeon had repaired a soldier's skull defect by
      implanting dog bone with good results. Discovery of the anesthetics, nitrous
      oxide and ether, in addition to the introduction of antisepsis opened up new
      surgical possibilities and made bone grafting a possible clinical procedure.
      Around the turn of the last century, papers began to appear on the restoration of
      continuity defects of the mandibula. In the future it will be possible to acquire
      a living graft in the exact size desired based on a 3D reconstruction of a CT
      scan of the defect.

PMID- 11974548
TI  - Many leads, many dead ends. Frustration inside the FBI's anthrax investigation: a
      so-far perfect crime.

PMID- 11974549
TI  - Healthcare headaches.

PMID- 11974550
TI  - Schools of medicine. Top schools--research.

PMID- 11974551
TI  - Plastic price cuts? Drug discount cards shave but don't slash high bills. And
      most aren't free.

PMID- 11974552
TI  - Doubts of a doctor. A new book reveals remarkable uncertainties that hide behind
      the sure hands of your surgeon. Interview by Linda Kulman.

PMID- 11974553
TI  - The good seed. By deciphering the DNA sequence of rice, scientists hope to glean
      clues to richer harvests.

PMID- 11974554
TI  - The bleeding problem.

PMID- 11974555
TI  - Defining 'relative' androgen deficiency in aging men: how should testosterone be
      measured and what are the relationships between androgen levels and physical,
      sexual and emotional health?
AB  - In men, bioavailable and free testosterone levels decline by about 1.0 and 1.2%
      per year, respectively, after the age of 40. The definition of clinically
      relevant androgen deficiency in the aging male remains uncertain. Clinical
      features common to both aging and androgen deficiency include decreased muscle
      mass and strength, and increased fatigue, increased fat mass, loss of libido,
      erectile dysfunction, impaired cognitive function and depression. It is, however,
      difficult to separate the effect on plasma testosterone of concomitant disease,
      compared with the effects of a decrease in testosterone levels alone.
      Testosterone supplementation has been shown to be effective in improving many of
      the clinical features of androgen deficiency in the older male, and is safe, at
      least in the short term. The maximum benefit occurs in those men with the lowest
      testosterone levels.

PMID- 11974556
TI  - Endometrial safety and bleeding patterns during a 2-year study of 1 or 2 mg 17
      beta-estradiol combined with sequential 5-20 mg dydrogesterone.
AB  - OBJECTIVE: To assess the endometrial safety and bleeding patterns of 17 beta
      estradiol sequentially combined with dydrogesterone. METHODS: Endometrial safety
      and bleeding patterns were assessed in 579 postmenopausal women randomized to
      oral treatment with placebo, 1 mg/day 17 beta-estradiol sequentially combined
      with 5 or 10 mg/day dydrogesterone for the last 14 days of each 28-day cycle, or
      2 mg/day 17 beta-estradiol sequentially combined with 10 or 20 mg/day
      dydrogesterone for the last 14 days of each 28-day cycle. Treatment was continued
      for 26 cycles. Proliferative endometrium, endometrial hyperplasia and endometrial
      malignancy in the end-of-study biopsy were considered as inadequate
      progestational responses. RESULTS: Biopsies were not available in 137 women
      mainly because of an insufficient treatment period or non-compliance. An adequate
      progestational response was seen in more than 98% of the 442 women who underwent
      biopsy after treatment. Bleeding data were not available in 193 women, most of
      whom did not remain on treatment for the full 26 cycles. The 1-mg 17 beta
      estradiol dose was associated with less cyclic and intermittent bleeding than the
      2-mg dose. Higher doses of dydrogesterone were associated with a higher incidence
      of cyclic bleeds and a later day of onset, while duration, severity and
      regularity were similar in all groups irrespective of estradiol or dydrogesterone
      dose. CONCLUSION: Sequential combinations of 1 mg 17 beta-estradiol with 5 or 10
      mg dydrogesterone and 2 mg 17 beta-estradiol with 10 or 20 mg dydrogesterone are
      associated with very good endometrial safety. The incidence of bleeding is lower
      with the 1-mg dose of 17 beta-estradiol.

PMID- 11974557
TI  - Estrogen and colon cancer: current issues.
AB  - Carcinoma of the colon is common and its incidence varies according to the
      geographical location and dietary habits. The aims of this paper are, first, to
      review the current epidemiological data on the incidence and mortality of colon
      cancer in postmenopausal women using hormone replacement therapy (HRT); second,
      to review the published data on the prevalence of estrogen receptors in healthy
      and malignant colonic tissue; and third, to examine the available evidence of
      gene silencing as applicable to this and other neoplastic conditions. Estrogen
      use confers overall protection, with a reduction in the incidence of colon
      adenoma and carcinoma of about 30%. Estrogen use reduces the colon cancer-related
      mortality. The risk of colon cancer is decreased among current and recent users
      of postmenopausal HRT but the molecular mechanisms involved remain unclear.
      Estrogen acts either on a single major transformation step in the oncogenetic
      process, or is involved in multiple events that avert the course of this
      transformation. Aberrant methylation of the CpG islands in the promoter regions
      of the estrogen receptor gene, as well as of other genes, is equivalent to the
      silencing of that gene, with the consequence of inactivation, or reduced
      expression, of a number of genes downstream, including tumor suppressor genes.
      This epigenetic mechanism, when reversed, suppresses the growth of cancer cells
      in vitro and in vivo. The ubiquitous distribution of the estrogen receptor genes
      and their isoforms, in a tissue-specific manner, opens new avenues for the
      understanding of cellular behavior in health and disease.

PMID- 11974558
TI  - Estradiol and levonorgestrel: effects on bleeding pattern when administered in a
      sequential combined regimen with a new transdermal patch.
AB  - OBJECTIVE: A 1-year, randomized, multicenter study was carried out to assess the
      effects of estradiol/levonorgestrel, delivered transdermally by 7-day patches in
      a sequential combined regimen, on bleeding pattern and acceptability in
      postmenopausal women. METHODS: A total of 468 postmenopausal women were
      randomized to 15-cm2, 22.5-cm2 or 30-cm2 patches containing 17 beta-estradiol
      alone (50, 75 or 100 micrograms/24 h, respectively) for 2 weeks followed by 17
      beta-estradiol/levonorgestrel (50/10, 75/15 or 100/20 micrograms/24 h) for 2
      weeks. RESULTS: The occurrence of cyclic bleeds was dose-dependent, with an
      increase at higher dosages; the frequency of a cyclic bleed per treatment cycle
      was 40% in the 50/10 micrograms/24 h patch, 62% in the 75/15 micrograms/24 h
      patch and 76% in the 100/20 micrograms/24 h patch. The incidence of intermittent
      bleeding also increased with higher doses, from 22% in the 50/10 group to 35% in
      the 100/20 group; 20% of women in the 50/10 group did not bleed at all; the
      corresponding figures for the 75/15 and 100/20 groups were 7% and 0%,
      respectively. Time of onset of cyclic bleeding was constant in all groups. The
      mean duration of cyclic bleeding was constant within each group, but increased
      from 4.4 days in the 50/10 to 6.3 days in the 100/20 group. The regularity and
      predictability of cyclic bleeding were high in all groups. Recurrence of cyclic
      bleeds was acceptable for most women (90%). CONCLUSIONS: Sequential combined
      transdermal 17 beta-estradiol/levonorgestrel shows very good cycle control that
      is well accepted by postmenopausal women.

PMID- 11974559
TI  - The assessment of bleeding patterns in postmenopausal women during continuous
      combined hormone replacement therapy: a review of methodology and recommendations
      for reporting of the data.
AB  - OBJECTIVES: To systematically review methods used to report data on bleeding
      patterns among postmenopausal women enrolled in clinical trials of continuous
      combined hormone replacement therapy (HRT); and to propose the use of
      standardized terms, definitions, and methods for collecting and reporting
      bleeding data in such trials. METHODS: A MEDLINE search identified 18 published
      reports of bleeding patterns among postmenopausal women enrolled in prospective
      clinical trials that included a continuous combined HRT treatment arm. Only two
      of these trials were not randomized. Methods for collecting and analyzing
      bleeding pattern data were collated from these published reports and examined for
      consistency. RESULTS: Comparisons across studies revealed little consistency in
      definitions and indices utilized to report bleeding patterns among postmenopausal
      women administered continuous combined HRT regimens in clinical trials. While a
      majority of the trials incorporated definitions established by the World Health
      Organization for the evaluation of bleeding with hormonal contraception, a number
      of the studies expanded on these definitions to reflect additional dimensions of
      bleeding such as volume. Indices calculated from daily bleeding data to describe
      bleeding patterns in treatment groups were highly variable among studies.
      CONCLUSION: Inconsistencies among clinical trials in bleeding pattern definitions
      and indices limit understanding and comparison of typical bleeding patterns with
      continuous combined HRT regimens. Standardized definitions, data collection
      procedures, and indices are proposed to enhance understanding of bleeding
      patterns with hormone therapy and enrich the quality of patient counselling on
      HRT.

PMID- 11974560
TI  - A randomized, open-label study of conjugated equine estrogens plus
      medroxyprogesterone acetate versus tibolone: effects on symptom control, bleeding
      pattern, lipid profile and tolerability.
AB  - OBJECTIVE: To compare the effects of continuous combined conjugated equine
      estrogens plus medroxyprogesterone acetate (CEE/MPA) with those of tibolone on
      symptom control, bleeding pattern, lipid profile and tolerability in
      postmenopausal women. METHODS: This was a randomized, open-label, parallel-group,
      multicenter study. Generally healthy postmenopausal women with an intact uterus
      and no contraindications to hormone replacement therapy (HRT) or tibolone were
      enrolled. Each subject was randomly assigned to receive CEE/MPA 0.625 mg-5.0 mg
      or tibolone 2.5 mg daily for 13 treatment cycles, each of 28 days. RESULTS: A
      total of 85 subjects were enrolled and received at least one dose of study
      medication, of which 76 (89.4%) subjects completed the study (n = 40, CEE/MPA; n
      = 36, tibolone). The incidence of postmenopausal symptoms decreased significantly
      over time in both treatment groups, compared with baseline, including significant
      decreases in the incidence of urogenital and sexual health symptoms. Significant
      differences in symptom control (other than hot flushes) were observed between
      treatment groups in a few different cycles for different symptoms, but no
      consistent or clinically significant trends were observed. No statistically
      significant differences in the incidence of bleeding were observed between
      treatment groups after cycle 4. Significant decreases in total cholesterol (5.6%)
      and low-density lipoprotein (LDL) cholesterol (7.5%) were observed at cycle 13,
      compared with baseline, in the CEE/MPA group, and significant decreases in high
      density lipoprotein (HDL) cholesterol (8.5%) and triglycerides (13.7%) were
      observed at cycle 13, compared with baseline, in the tibolone group. Significant
      weight gain was observed at cycle 13 in the tibolone group (3.05 kg), compared
      with the CEE/MPA group (0.96 kg). The incidences of adverse events were similar
      in both treatment groups. CONCLUSIONS: Women treated with CEE/MPA or tibolone
      showed significant improvement of postmenopausal symptoms, including urogenital
      and sexual health symptoms, and had similar bleeding patterns after four cycles
      of therapy. CEE/MPA and tibolone each induced a different mix of changes in the
      lipid profile.

PMID- 11974561
TI  - Validation of Italian version of the Women's Health Questionnaire: assessment of
      quality of life of women from the general population and those attending
      menopause centers.
AB  - OBJECTIVES: The Women's Health Questionnaire has been developed and validated in
      Anglo-Saxon and Swedish populations. The purpose of this study was to evaluate
      the Italian version of the questionnaire to determine whether cross-cultural
      differences exist in the perception of quality of life, and to use it to compare
      the quality of life in women attending menopause centers with that of women in
      the general population. METHODS: An Italian version of the Women's Health
      Questionnaire (WHQ) was produced, using the forward-backward translation method
      to ensure conceptual equivalence, and approved by the originator. Women were
      recruited by random selection from the general population and from menopause
      centers, those taking hormone replacement therapy being ineligible. The
      questionnaire was completed anonymously at home and mailed to the co-ordinating
      center. Psychometric evaluation included tests of item convergent and
      discriminant validity, internal-consistency reliability, test-retest reliability,
      construct validity and the discriminative properties of the questionnaire.
      RESULTS: The completeness of the data was good, with missing-value rates
      consistently low for most items. Item-scale correlations, used to evaluate
      internal consistency, were also good and the scaling success rate, used to
      measure item discriminant validity, was high for all scales. Scale scores were
      reliable for seven out of nine scales and test-retest reliability was excellent.
      There were few significant differences between the two populations of women in
      most of the WHQ areas. A comparison of Italian data with published data on
      English women showed great similarity. CONCLUSION: The Italian version of the WHO
      is valid and reproducible. The subjective perception of the menopause and its
      related problems is similar in geographically and culturally different
      populations.

PMID- 11974562
TI  - Experiences at menopause of women in a non-English-speaking community: a
      qualitative study.
AB  - CONTEXT: It is important that clinicians appreciate the link between
      physiological disturbances and cultural meanings. The community surrounding the
      Baker Medical Research Institute in Melbourne, Australia includes a substantial
      number of women from a Greek-speaking background who attend the Menopause Clinic.
      OBJECTIVE: To demonstrate how qualitative methodologies can assist with the
      development of clinical services by employing them to elucidate the role of
      cultural variables in the ways in which Greek women view menopause, aging,
      illness and medicine. DESIGN: This was a qualitative study employing in-depth
      interviews on five separate occasions over 2 years, analyzed with thematic and
      ethnographic content analysis. PATIENTS: Subjects were 40 Greek-speaking women
      attending the Clinic, aged 45-60 years. RESULTS: There is an intricate
      association between experiences of the menopause and family relationships,
      problems raised by immigration and the cultural dislocation caused by it, beliefs
      and theories of the body, religion, and traditional approaches to healing and
      medicine. Many women had experienced unfavorable or unsatisfactory encounters
      with medicine in the past, reflecting lack of understanding of the women's
      experiences and failures of communication about clinical assessments and
      recommended treatments. Traditional therapies were often used without advising
      doctors. CONCLUSIONS: The study emphasizes the potential utility of qualitative
      research methods for improving clinical practice by elaborating the specific
      requirements of particular groups, and thereby allowing doctors to deliver
      services that are more acceptable to patients from both a cultural and an ethical
      point of view, and also more effective. The process established for the evolution
      of our clinic may serve as a model for other clinics seeking to direct themselves
      to the needs of particular social groups or communities.

PMID- 11974564
TI  - Menopause World Congress in Berlin.

PMID- 11974563
TI  - Thrombophilic profile of climacteric and menopausal women with venous
      thromboembolism.

PMID- 11974565
TI  - How reliably does 12-month amenorrhea define final menstrual period? Data from a
      longitudinal study.

PMID- 11974566
TI  - Mammographic density changes in women on hormone replacement therapy.

PMID- 11974567
TI  - Treatment can lead to a long dry spell.

PMID- 11974568
TI  - Getting the word out.

PMID- 11974569
TI  - The numbers lie.

PMID- 11974570
TI  - Eroding the quality of life.

PMID- 11974571
TI  - Case manager role. A content analysis of published literature.
AB  - The case manager (CM) role is in its third decade of existence. However, there
      remains a lack of continuity in definition, educational level and qualifications,
      and the needed experience for role performance. This article presents the results
      of a content analysis of the published literature, conducted at two points in
      time, in an attempt to clarify common qualifications and skills needed for role
      implementation. The results suggest that the CM role requires interpersonal
      skills, and knowledge of planning, economic and evaluation strategies. Comparison
      of data for the two measurement times revealed an increased emphasis on the need
      to work in groups, conduct cost accounting, and facilitate change. Outcome
      measurement and ongoing evaluation experienced a decline in importance at the
      time of the second analysis. The ability to critically think, communicate and
      practice with clinical expertise emerge as inherent qualities of the role.
      Educational and experiential background remain ill defined in the literature.

PMID- 11974572
TI  - Looking beyond caseload numbers for long-term home-care case managers.
AB  - Determining the best use of case managers' time is difficult both because of the
      great variability in the factors and the lack of outcome studies. In place of the
      outcome studies, the responses to focus group questions of 89 experienced case
      managers from across Canada were used to indicate a value for case management
      functions in the areas of direct care, indirect care management, and program
      management. The case managers identified greater value for direct care with
      clients and families who are new to home care or who have complex problems in
      comparison to clients in more stable or manageable situations. Case managers were
      frustrated by the lack of agency and community policies and resources to allow
      case managers to properly support people in their homes. The case managers valued
      addressing problems on a program or community basis rather than the usual case-by
      case. Although preliminary, the approach could be useful in assessing the
      efficient and effective use of a scarce resource, case managers' time.

PMID- 11974573
TI  - Challenges facing case management in a changing social service environment.
AB  - Case management has been a difficult practice to track, particularly for the
      purposes of outcome measurements and accountability. As both policymakers and
      program administrators consider options for providing long-term care, the Data
      Analysis and Regulations Team of the California Department of Aging studied
      computerized client information for one of its case management programs to
      examine what we know about the people being served and the ability of the data
      collection system to meet the increasing demand for accountability. This article
      details the results of our study and discusses their implications within the
      dynamics of a changing social service environment.

PMID- 11974575
TI  - Care needs of older Broome County residents. A survey of elders receiving care
      through the continuum.

PMID- 11974574
TI  - An older rural widow's transition from home care to assisted living.
AB  - Designed to foster appreciation of comprehensive evaluation of home care
      outcomes, this case study of an older rural widow is part of a longitudinal
      phenomenological study of home care. Over 14 months, while her home care agency
      reacted to the Balanced Budget Act, nine interviews were done with a 95-year-old
      woman who lived alone until she moved to an assisted living facility. Data
      analysis yielded structures of her changing experience of home care. Although
      primarily supportive services may have been inconsistent with Medicare
      regulations, such services may have influenced the favorable outcomes of
      sustaining elders at home and undergirding the rural economy.

PMID- 11974576
TI  - Control beliefs of the frail elderly. Assessing differences between homebound and
      nursing home residents.
AB  - Previous age-related sense of control studies have largely focused on active,
      community-dwelling aged individuals and have excluded elderly persons who are
      frail. This study compares sense of control and life satisfaction as determined
      through rating scale administration between two frail, dependent samples: nursing
      home residents and homebound elderly. Differences in control scores were
      statistically significant for those who were homebound expressing higher
      perceived personal control than nursing home residents (p < .001). Sense of
      control has no correlation with either life satisfaction or length of stay in the
      nursing home cohort.

PMID- 11974577
TI  - The use of the Minimum Data Set. Home Care in a case management project in Hong
      Kong.
AB  - 130 hospital-discharged elderly patients received our comprehensive assessment by
      using a Chinese Minimum Data Set-Home Care (MDS-HC). Our case manager developed
      and implemented care plans with reference to the computer-generated Clients
      Assessment Protocols. Results showed that the MDS-HC was sensitive to identify
      elderly persons' holistic needs, and helpful in formulating all-inclusive care
      plans.

PMID- 11974578
TI  - The effects of aging on lymphocyte development and function: introduction.

PMID- 11974579
TI  - Regulation of telomerase expression in human lymphocytes.
AB  - The function of lymphocytes is highly dependent on the ability of cell to divide.
      Among the various factors that regulate this cellular process, telomerase
      dependent maintenance of telomere length has recently drawn considerable
      attention. Unlike most normal human somatic cells that express telomerase only
      during development but not after differentiation, lymphocytes express telomerase
      during development and retain the ability to express telomerase after maturation
      in response to antigenic challenge. How telomerase is regulated and its precise
      role in lymphocytes is not fully understood. The recent progress in
      characterizing regulation of telomerase expression in human lymphocytes is
      discussed.

PMID- 11974580
TI  - The effect of age on B cell development and humoral immunity.

PMID- 11974581
TI  - Effect of age on naive CD4 responses: impact on effector generation and memory
      development.

PMID- 11974582
TI  - Biochemical and genetic analyses of T cell aging in mice.

PMID- 11974583
TI  - Current concepts of thymic aging.

PMID- 11974585
TI  - Age-associated changes in thymopoiesis.

PMID- 11974584
TI  - Immunosenescence phenotypes in the telomerase knockout mouse.
AB  - Increasing generations of the telomerase knockout mouse, Terc-/-, show severe
      telomere dysfunction characterized by critically short telomeres and end-to-end
      chromosomal fusions. These mice also suffer from various age-related diseases
      affecting highly proliferative tissues. Among these pathologies are a reduced
      proliferative capacity of B and T cells, as well as a reduction of germinal
      center reactivity upon immunization. Both immune system defects are landmarks of
      immunosenescence. The study of the telomerase-deficient mouse model supports the
      notion that telomere shortening with age contributes to immunological dysfunction
      in the elderly.

PMID- 11974587
TI  - [Photoprotective mechanisms of human skin. Modulation by oligonucleotides].
AB  - There are at least two classic photoprotective DNA damage responses that can be
      elicited by UV exposure: induction of melanogenesis (tanning) and enhancement of
      DNA repair. Both mechanisms are mediated, at least in part, by the tumor
      suppressor protein and transcription factor p53. Both of these responses can be
      induced in vitro as well as in vivo by small DNA fragments of specific sequences,
      without prior induction of actual DNA damage. The topical application of such
      fragments onto human skin might enhance photoprotection in human skin, as
      typically elicited by gradual sun exposure. The induction of photoprotection by
      this means, however, would not bear the mutagenic and carcinogenic risk of
      exposure to natural sunlight.

PMID- 11974588
TI  - [Cutaneous microdialysis. Use in dermatology].
AB  - The determination of concentrations of exogenous or endogenous substances in the
      dermis, e.g. for pharmacokinetic studies, is technically difficult. Performing
      skin biopsies or inducing suction blisters results in the disintegration of the
      tissue and allows only single measurements. Recently, cutaneous microdialysis, a
      new simple and minimally invasive technique for continuously measuring of
      substances in the dermis in vivo, has been introduced in dermatological research.
      According to the principle of dialysis, a semipermeable membrane is inserted in
      the dermis and due to a concentration gradient between the interstitial space and
      a perfusate, substances diffuse through the pores of the membrane and can be
      analyzed in the dialysate. Cutaneous microdialysis represents a useful technique
      for pharmacokinetic or pharmacodynamic studies as well as for investigations
      regarding cutaneous physiology and pathophysiology.

PMID- 11974586
TI  - [Do sulfonamides still retain a place in dermatological therapy?].

PMID- 11974589
TI  - [Special aspects for preventing thromboembolism in surgical dermatology].

PMID- 11974590
TI  - [Nutritional status of adult patients with atopic dermatitis].
AB  - Many atopic dermatitis (AD) patients follow elimination diets for long periods of
      time because of true or--even more often--suspected food allergies or
      hypersensitivities. In the present study we investigated the nutritional status
      of adult AD patients by evaluating food intake protocols followed by measuring
      different serum parameters. Evaluation of the food intake protocols over 3 days
      (n = 47) showed that the total calorie intake met recommended intake in 12
      patients (group A), ranged between 75-100% of the requirements in 23 patients
      (group B) and was 50-75% in 12 patients (group C). The relative intake of
      different nutritional factors approached normal limits in group A and B; the
      intake of several of these factors was significantly decreased in group C.
      Various serum parameters in group C patients were different from those found in
      patients suffering from other chronic skin diseases. Taken together, our results
      show that a subgroup of AD patients have dietary habits which result in
      significant nutritional deficiency which are important for homeostasis. This
      indicates the necessity of professional guidance in these patients in order to
      only eliminate foods which have been proven to elicit adverse reactions by oral
      provocation tests.

PMID- 11974591
TI  - [Recurrence of an epithelioid sarcoma of the scalp].
AB  - Epithelioid sarcoma is a rare soft tissue tumor that, due to its clinically
      unspecific features, is frequently mistaken for other benign and malignant
      entities. We report on a 63-year-old male presenting with a relapse of an
      epithelioid sarcoma. At clinical inspection, the tumor presented as an
      erythematous nodule with ulceration in the center. Despite its slow growth,
      epithelioid sarcoma should be regarded as an aggressive neoplasm exhibiting
      frequent local recurrences and subsequent lymphatic and visceral spreading in
      about half of the patients. Histopathological findings are the presence of large
      epithelioid and spindle cells with immunoreactivity for cytokeratin and vimentin.

PMID- 11974592
TI  - [Allergic reaction after contact with Hura crepitans (sandbox tree)].
AB  - We describe a 36-year-old female patient with angioedema-like swellings and
      rhinoconjunctivitis for 1 year occurring exclusively at her home. The clinical
      history revealed no correlation with foods, food additives, drugs, or
      aeroallergens. The complaints always started immediately after contact with the
      sandbox tree (Hura crepitans) placed in her apartment. Scratch testing resulted
      in a two-fold positive reaction towards leaves and stem, while five controls
      remained negative. Thus we suggest the reaction of the patient to be allergic in
      nature. Hura crepitans belongs to the family of Euphorbiaceae, whose largest
      genera are Euphorbia and Croton. The toxic reactions to the milky sap, the so
      called latex, of these plants are caused by ingredients such as phorbol esters,
      croton oil, lectins, and terpens. Various terpens are also well known as
      allergens. Phytotoxic and phytoallergic reactions are growing increasingly
      important and should therefore be included in the differential diagnosis in
      dermatology.

PMID- 11974593
TI  - [Eosinophilic ulcer of the mouth mucosa. Differential mouth ulcer diagnosis].
AB  - Eosinophilic ulcers of the oral mucosa represent a rare, self-limiting disease of
      unknown origin. Single lesions occur typically in the oral cavity or on the lower
      lip. Characteristically, they have a short history and resolve spontaneously.
      Diagnosis is verified by the histologic feature of a deep polymorphic
      inflammatory infiltrate with numerous eosinophils. The clinical aspect shows a
      usually nontender ulcer with a white or yellowish base and elevated indurated
      borders or a tumor with central ulceration. Lymphadenopathy is not found.
      Differential diagnoses include malignant tumors and the primary stage of
      syphilis. We present three cases recently diagnosed in our department to show the
      characteristics and the different appearances of the disease. A 74-year-old woman
      presented with an ulcer at the base of the tongue, a 59-year-old man had one on
      the lower lip, and in a 48-year-old man the lesion was atypically located at the
      edge of the mouth. Here we demonstrate the importance of knowledge of the
      disease, its course, and the characteristic histology to avoid troublesome
      diagnostic and therapeutic procedures.

PMID- 11974595
TI  - [Bullous autoimmune dermatoses. 1: Classification].

PMID- 11974596
TI  - [4th International Conference on Varicella, Herpes Zoster and Postherpetic
      Neuralgia (PHN). 3-5 March 2001, La Jolla, California, USA].

PMID- 11974594
TI  - [Vesicle, light hypersensitivity, mouth ulceration and arthralgia in a 40-year
      old patient. Bullous systemic lupus erythematosus].

PMID- 11974597
TI  - [Is general discontinuation of sulfonamides in external therapy justified?].

PMID- 11974598
TI  - [Otto Braun-Falco Alumni Lecture 21 July 2001 in Zurich].

PMID- 11974599
TI  - The biological improbability of a clone.
AB  - Empirical evidence for intraclonal genetic variation is described here for clonal
      systems using a variety of molecular techniques and implicating a diversity of
      mechanisms. However, clonal systems are still generally perceived as having
      strict genetic fidelity. As concepts of genetic variability move from primary
      sequence data to include epigenetic and structural influences on genetic
      expression, the ability to detect changes in the genome at short intervals allows
      precedence to be given to inherent biological variation that is often
      analytically ignored. Therefore, the advent of powerful molecular techniques,
      like genome mapping, mean that our concepts of genetic fidelity within eukaryotic
      clones and the whole philosophy of the 'clone' needs to be re-evaluated and
      redefined to replace old unproven dogma in this aspect of science.

PMID- 11974600
TI  - Evidence for dynamic alteration in histone gene clusters of Caenorhabditis
      elegans: a topoisomerase II connection?
AB  - Chromatin integrity is maintained throughout the cell cycle through repair
      mechanisms and intrinsically by the ordered packaging of DNA in association with
      histone proteins; however, aberrant rearrangements within and between chromosomes
      do occur. The role of the nuclear matrix protein topoisomerase II (TopoII) in
      generating chromosome breakpoints has been a focus of recent investigations.
      TopoII preferentially binds in vitro to scaffold-associated regions (SARs) and is
      involved in many DNA processing activities that require chromosome untangling.
      SARs, biochemically defined DNA elements rich in A + T, have been proposed to
      serve as structural boundaries for chromatin loops and to delineate functional
      domains. In our investigation of gene compartmentalization in a eukaryotic
      genome, SAR-associated nucleotide motifs from Drosophila were mapped in the
      regions of three histone gene clusters in an in silico analysis of the genome of
      Caenorhabditis elegans. Sites with similarity to the 15 bp consensus for TopoII
      cleavage were found predominantly in A + T enriched intergenic regions.
      Reiteration of sites matching the TopoII core consensus led to the identification
      of a novel core histone gene on chromosome IV and provided evidence for
      duplication and inversion in each of the three histone gene clusters. Breakpoint
      analysis of DNA flanking reiterated regions revealed potential sites for TopoII
      cleavage and a base composition phenomenon suggestive of a trigger for inversion
      events.

PMID- 11974601
TI  - Genetic study of the production of sexually dimorphic cuticular hydrocarbons in
      relation with the sex-determination gene transformer in Drosophila melanogaster.
AB  - In Drosophila melanogaster, the main cuticular hydrocarbons (HCs) are some of the
      pheromones involved in mate discrimination. These are sexually dimorphic in both
      their occurrence and their effects. The production of predominant HCs has been
      measured in male and female progeny of 220 PGa14 lines mated with the feminising
      UAS-transformer transgenic strain. In 45 lines, XY flies were substantially or
      totally feminised for their HCs. Surprisingly, XX flies of 14 strains were
      partially masculinised. Several of the PGa14 enhancer-trap variants screened here
      seem to interact with sex determination mechanisms involved in the control of
      sexually dimorphic characters. We also found a good relationship between the
      degree of HC transformation and GAL4 expression in oenocytes. The fat body was
      also involved in the switch of sexually dimorphic cuticular hydrocarbons but its
      effect was different between the sexes.

PMID- 11974602
TI  - Insecticide resistance genes induce a mating competition cost in Culex pipiens
      mosquitoes.
AB  - Resistance to organophosphorus insecticides (OP) in Culex pipiens mosquitoes
      represents a convenient model for investigating the fitness cost of resistance
      genes and its origin, since both the environmental changes in nature and the
      adaptive genes are clearly identified. Two loci are involved in this resistance-
      the super-locus Ester and the locus Ace.1--each displaying several resistance
      alleles. Population surveys have shown differences in fitness cost between these
      resistance genes and even between resistance alleles of the same locus. In order
      to better understand this fitness cost and its variability, the effects of these
      resistance genes on several fitness-related traits are being studied. Here,
      through competition experiments between two males for the access to one female,
      we analysed the effect on paternity success associated with three resistance
      alleles--Ester4, Ester1 and Ace.1R--relative to susceptible males and relative to
      one another. The eventual effect of female genotype on male mating success was
      also studied by using susceptible and resistant females. The strains used in this
      experiment had the same genetic background. Susceptible males had a mating
      advantage when competing with any of the resistant males, suggesting a
      substantial cost of resistance genes to this trait. When competing against
      susceptible males, the paternity success did not vary among resistant males,
      whatever the genotype of the female. When competing against other resistant
      males, no difference in paternity success was apparent, except when the female
      was Ester1.

PMID- 11974603
TI  - Chromosomal inversion polymorphism in Afrotropical populations of Drosophila
      melanogaster.
AB  - When 41 populations from Africa (south of the Sahara) and Indian Ocean islands
      were analysed for their chromosomal inversion polymorphism, 34 rearrangements
      were found, including the four common cosmopolitans (In(2L)t, In(2R)NS, In(3L)P
      and In(3R)P), four rare cosmopolitans (In(2L)NS, In(3R)C, In(3R)Mo and In(3R)K)
      and six African polymorphic ('recurrent') endemics. Mean inversion frequencies
      per major autosome arm were positively and, generally, highly correlated to each
      other. There was no altitudinal nor latitudinal cline of inversion frequency,
      except for one African polymorphic endemic. Significant longitudinal clines were
      detected for In(2L)t, In(3L)P and In(3R)K; in all cases, inversion frequencies
      decreased eastward. Principal components analysis and ANOVA made it possible to
      distinguish three groups of populations. A high level of polymorphism was found
      in populations from west tropical Africa. The other low altitude populations from
      the mainland were moderately polymorphic, whereas the lowest levels of
      polymorphism were those of high altitude populations and of Indian Ocean islands.
      Moreover, some regional and local differentiation was also found. The frequency
      of unique autosomal inversions was not different from those found in Asia,
      Australia and America, but was significantly higher than that in Europe and North
      Africa. A West-East differentiation was also observed for the African polymorphic
      endemics. The present geographic pattern suggests a long, patchy evolution with
      restricted gene flow, followed by the modern period with numerous recent
      migrations linked to human transportation.

PMID- 11974604
TI  - An introgression approach to mapping differences in mating success and sperm
      competitive ability in Drosophila simulans and D. sechellia.
AB  - The progeny of Drosophila females doubly-mated to males from the same and a
      closely related species are mostly sired by conspecific males. We examined the
      genetic basis for conspecific mating preference and sperm precedence by using 186
      Drosophila lines in which random chromosomal fragments of D. sechellia were
      introgressed into D. simulans. Sperm competition was measured for each of these
      lines by crossing ebony D. simulans female with ebony D. simulans males followed
      by wild-type males from the introgressed lines. Variation in sperm competition
      (proportion of progeny sired by the second male), mating discrimination
      (proportion of introgressed males that failed to remate), and male fecundity
      (proportion of progeny sired by introgressed males) were scored. The introgressed
      lines exhibited highly significant heterogeneity in the three phenotypes scored,
      motivating an analysis to locate quantitative trait loci (QTLs) responsible for
      the differences. Applying composite interval mapping, we found eight QTLs that
      explain a significant level of variation among introgressed lines in the
      phenotypes scored. Cytological position overlapped among some QTLs suggesting
      possible pleiotropic effects. Analysis of the joint effects of simulans/sechellia
      genetic composition at different QTLs and markers suggests that complex
      interactions among alleles are partially responsible for interspecific
      differences in sexual traits.

PMID- 11974605
TI  - Comparison of methods used for recovering the line origin of alleles in a cross
      between outbred lines.
AB  - Here, we introduce the idea of probabilities of line origins for alleles in
      general pedigrees as found in crosses between outbred lines. We also present
      software for calculating these probabilities. The proposed algorithm is based on
      the linear regression method of Haley, Knott and Elsen (1994) combined with the
      Markov chain Monte Carlo (MCMC) method for estimating quantitative trait locus
      coefficients used as regressors. We compared the relative precision of our method
      and the original method as proposed by Haley et al. (1994). The scenarios studied
      varied in the allelic distribution of marker alleles in parental lines and in the
      frequency of missing marker genotypes. We found that the MCMC method achieves a
      higher accuracy in all scenarios considered. The benefits of using MCMC
      approximation are substantial if the frequency of missing marker data is high or
      the number of marker alleles is low and the allelic frequency distribution is
      similar in both parental lines.

PMID- 11974606
TI  - Linkage mapping of sex-specific differences.
AB  - Most current linkage analyses assume identical fractions of meiotic recombination
      between homologous marker loci of the two sexes. This assumption is not
      realistic, because considerable sex-related differences have been observed in
      recombination fraction. In this paper, a general EM-based algorithm is presented
      to estimate sex-specific recombination fractions for a mixed set of molecular
      markers segregating differently in a full-sib family derived from two
      heterozygous parents. The asymptotic variances of the estimates of linkage
      specifically for each of the parents are evaluated using a numerical analysis
      based on information functions. This approach will have important implications
      for precise gene mapping based on sex-specific linkage maps.

PMID- 11974607
TI  - On the mapping of quantitative trait loci at marker and non-marker locations.
AB  - Previous studies have noted that the estimated positions of a large proportion of
      mapped quantitative trait loci (QTLs) coincide with marker locations and have
      suggested that this indicates a bias in the mapping methodology. In this study we
      predict the expected proportion of QTLs with positions estimated to be at the
      location of a marker and further examine the problem using simulated data. The
      results show that the higher proportion of putative QTLs estimated to be at
      marker positions compared with non-marker positions is an expected consequence of
      the estimation methods. The study initially focused on a single interval with no
      QTLs and was extended to include multiple intervals and QTLs of large effect.
      Further, the study demonstrated that the larger proportion of estimated QTL
      positions at the location of markers was not unique to linear regression mapping.
      Maximum likelihood produced similar results, although the accumulation of
      positional estimates at outermost markers was reduced when regions outside the
      linkage group were also considered. The bias towards marker positions is greatest
      under the null hypothesis of no QTLs or when QTL effects are small. This study
      discusses the impact the findings could have on the calculation of thresholds and
      confidence intervals produced by bootstrap methods.

PMID- 11974608
TI  - In plain sight.

PMID- 11974609
TI  - At your own risk. Some patients join clinical trials out of desperation, others
      to help medicine advance. Who is to blame if they get sick--or even die?

PMID- 11974610
TI  - The day the shots ran out.

PMID- 11974611
TI  - Tough kids, tougher calls.

PMID- 11974612
TI  - Viral, parasitic and prion diseases of farmed deer and bison.
AB  - The most important viral disease of farmed deer and bison is malignant catarrhal
      fever. The other herpesviruses which have been isolated from these species are
      briefly described. Other viral agents that are recognised in these animals,
      including adenovirus, parapox, foot and mouth disease, bluetongue, epizootic
      haemorrhagic disease, bovine virus diarrhoea, rotavirus and coronavirus, are also
      discussed. Ectoparasites of importance in this group in various parts of the
      world include a variety of ticks, as well as lice, keds, Oestridae, mange mites
      and fire ants. Helminth parasites include liver flukes (Fascioloides and
      Fasciola), gastrointestinal nematodes of the family Trichostrongylidae, pulmonary
      lungworms of the genus Dictyocaulus and extra-pulmonary lungworms of the family
      Protostrongylidae. Chronic wasting disease is principally important in North
      America, where the disease occurs in wild cervids in a limited area and has been
      reported in farmed deer in a small number of states in the United States of
      America and one province in Canada. These diseases are summarised in terms of
      their classification, epidemiology, clinical signs, pathology, diagnosis,
      treatment and control.

PMID- 11974613
TI  - Bacterial diseases of farmed deer and bison.
AB  - The most important aerobic bacterial diseases of farmed deer and bison include
      bovine tuberculosis, Johne's disease (paratuberculosis), yersiniosis,
      leptospirosis, brucellosis, pasteurellosis, anthrax, salmonellosis and
      colibacillosis. Anaerobic bacterial infections affecting the same animals include
      necrobacillosis and a number of clostridial diseases such as tetanus, blackleg,
      malignant oedema and pulpy kidney. The relative importance of these diseases will
      vary throughout the world according to timing and circumstance, but bovine
      tuberculosis and Johne's disease are likely to present the most significant
      problems with respect to diagnosis, control, trade in live animals and the
      establishment of wildlife reservoirs of infection. The authors summarise the
      aetiology, the principal species of animal affected, geographical distribution,
      transmission, clinical signs, pathology, diagnosis, treatment and control of
      these diseases.

PMID- 11974614
TI  - Diseases of farmed crocodiles and ostriches.
AB  - Crocodiles and ostriches are very sensitive to stress, and the ideal conditions
      for intensive rearing have not yet been established. Consequently, mortality is
      often directly linked to conditions on the farm. Crocodile and caiman pox,
      adenoviral hepatitis, mycoplasmosis, chlamydiosis and coccidiosis are crocodile
      specific infections with reservoirs in wild populations and adult wild-caught
      breeding stock. Other important conditions are salmonellosis, non-specific
      septicaemia, trichinellosis, the nutritional diseases osteomalacia, fat necrosis
      and gout, as well as winter sores. The only ostrich-specific transmissible
      disease is libyostrongylosis. Other important conditions are Newcastle disease,
      avian influenza, fading chick syndrome, tibiotarsal rotation and enteritis. No
      cases of coccidiosis in ostriches have ever been confirmed.

PMID- 11974615
TI  - Brucellosis in wildlife.
AB  - Brucellae infections have been documented world-wide over the years in a great
      variety of terrestrial wildlife species. Recently, brucellae infections have also
      been reported in a wide variety of marine mammals. A very important consideration
      with regard to terrestrial brucellosis in wildlife is to distinguish between a
      spillover of infection from domestic animals and a sustainable infection in wild
      species. The probability of brucellosis becoming established and being
      sustainable in a species depends on a combination of factors including host
      susceptibility, infectious dose, contact with infected animals, management and
      environmental factors. In this context, the development of the game farming
      industry appears to have contributed to the re-emergence of brucellosis. The gold
      standard in brucellosis diagnosis remains the isolation of brucellae. If
      brucellosis is suspected in an animal or a wildlife population following positive
      serological results, attempts to isolate the organism should always be performed.
      The release of anti-brucellae vaccine strain in wildlife is of concern because
      this could lead to environmental contamination and infection of other wild
      species. Therefore, the appropriate dosage of the vaccine in target species as
      well as the safety of the vaccine in non-target species must be addressed in
      technical terms in order to assist decision-making regarding the management of
      wildlife brucellosis.

PMID- 11974616
TI  - Classical swine fever (hog cholera) in wild boar in Europe.
AB  - Classical swine fever (CSF) is of increasing concern in Europe where wild boar
      appear to play an important epidemiological role. In most parts of the continent,
      demographic trends are on the increase, due to improvement in game management. As
      a result of higher densities, populations become more susceptible to various
      infectious diseases, among which CSF is cause for particular concern. Wild boar
      do not appear to be a classic reservoir in most cases, but nevertheless may
      perpetuate foci of infection over the long term, constituting a real threat for
      the pig farming industry. Since the infection does not appear to spread easily in
      natural populations of free-ranging wild boars, control of the disease may be
      feasible. However, most of the appropriate measures, such as banning hunting, are
      not considered acceptable. Consequently, the expertise of wildlife disease
      specialists is required to help solve the problem when it occurs.

PMID- 11974617
TI  - Chronic wasting disease in deer and elk in North America.
AB  - Chronic wasting disease (CWD) has emerged as an important disease of wildlife in
      North America. The disease is a unique member of the transmissible spongiform
      encephalopathies (TSEs) or prion diseases, which naturally affect only a few
      species. Of the TSEs, CWD is the only one found in free-ranging species. However,
      interest in CWD has recently grown, by association with the better-known TSEs
      such as variant Creutzfeldt-Jakob disease of humans and bovine spongiform
      encephalopathy. Knowledge of the geographic distribution of CWD, though still
      limited, has greatly improved since the mid-1990s as a result of surveillance in
      free-ranging deer and elk and in commercially owned Rocky Mountain elk (Cervus
      elaphus nelsoni), and the disease has now been found in multiple areas of the
      plains and Rocky Mountain foothills of western North America. Studies of the
      biology and natural history of CWD over recent years have resulted in a better
      understanding of the pathogenesis and epidemiology of the disease. Early
      involvement of the lymphoid tissues of the alimentary tract during the incubation
      period of CWD suggests plausible routes for agent exit from an infected
      individual, such as in faeces or saliva. Chronic wasting disease is laterally
      transmitted and environmental contamination may play an important role in local
      maintenance of the disease. Studies on the epidemiology of CWD have led to the
      development of models to help explain the history of CWD and to simulate future
      impacts on deer and elk populations. Diagnostic tests have been improved,
      allowing diagnosis early in the incubation period, long before the appearance of
      clinical disease. Surveillance techniques and programmes have been developed and
      instituted by wildlife management agencies for free-ranging deer and elk and by
      state and federal agricultural agencies for privately-owned elk. During the
      1990s, perceptions of TSEs have altered dramatically; perhaps most remarkably,
      the goal of global eradication of all prion diseases is now being discussed.

PMID- 11974618
TI  - Tuberculosis in free-ranging wildlife: detection, diagnosis and management.
AB  - Mycobacterium bovis is emerging as an important pathogen of free-ranging wildlife
      in which it is a potential source of infection for domestic animals and a threat
      to valuable wildlife species. This review examines the procedures for the
      detection, diagnosis and management of M. bovis in wildlife populations. The ante
      mortem detection of M. bovis infection in wildlife is difficult, due to the
      common occurrence of subclinical infections and the deficiencies of the currently
      available diagnostic tests. Serological tests are insensitive, while tests
      measuring cell-mediated immune responses show promise, but have not been
      sufficiently developed for routine use in most species. The diagnosis of M. bovis
      in free-ranging wildlife relies on post-mortem examination supported by
      histopathology and microbiology. A feature of M. bovis infections is the
      variation in the appearance and distribution of lesions in the different host
      species. Bacterial culture remains the gold standard for diagnosis of
      tuberculosis, while histopathology is limited by the frequent inability to
      distinguish lesions caused by M. bovis from those produced by other mycobacterial
      species. Deoxyribonucleic acid (DNA) fingerprinting and advanced typing
      techniques are increasingly being used to unravel the epidemiology of
      mycobacterial infections, including tuberculosis in free-ranging wildlife. An
      understanding of the epidemiology is essential if procedures are to be developed
      for the management of tuberculosis in wildlife. Few management options are
      currently available, especially for protected wildlife. Vaccination is the
      subject of much research, but further developments are required before it can be
      used to control tuberculosis in any animals, let alone in free-ranging wildlife.

PMID- 11974619
TI  - Infectious keratoconjunctivitis of ibex, chamois and other Caprinae.
AB  - Infectious keratoconjunctivitis (IKC) caused by Mycoplasma conjunctivae is a
      highly contagious ocular infection which is common in domestic sheep and goats.
      In the European Alps, IKC is often observed in Alpine chamois (Rupicapra r.
      rupicapra) and in Alpine ibex (Capra i. ibex), but the disease has also been
      described in other wild Caprinae in the Pyrenees and in New Zealand. The
      infection is characterised by inflammation of the conjunctiva and cornea, and in
      the most advanced stages, the cornea is opaque or even perforated. In IKC
      outbreaks in chamois and ibex, spontaneous recovery is the most prevalent outcome
      of the disease. However, mortality can occasionally reach 30%. Recent studies in
      eastern Switzerland indicated that M. conjunctivae infection is not self
      maintained in chamois. In contrast, the disease is endemic and self-maintained in
      the domestic sheep population. Spillover of the agent from sheep living in
      proximity during summer may be the origin of point-source epidemics in wild
      Caprinae. Flies are likely to play a central role in interspecific transmission
      of M. conjunctivae on alpine meadows. When outbreaks of IKC occur in wildlife, a
      special effort should be made to avoid unnecessary human disturbance in affected
      areas. However, animals presenting irreversible ocular lesions should be shot by
      professional gamekeepers to prevent suffering. Prevention of IKC in wild Caprinae
      should focus on preventing the spillover of M. conjunctivae from livestock.
      However, studies are required to evaluate the distribution of M. conjunctivae
      infection in domestic sheep in several countries and to assess the risk of IKC
      spillover from domestic animals to wildlife. In addition, immunological studies
      should be performed to develop tools which could lead to the control of M.
      conjunctivae infection in domestic sheep.

PMID- 11974620
TI  - Rabbit haemorrhagic disease: field epidemiology and the management of wild rabbit
      populations.
AB  - Rabbit haemorrhagic disease (RHD) has become established in wild rabbit
      populations throughout Western Europe, Australia and New Zealand. The abundance
      of wild rabbits has been significantly reduced, particularly in drier areas of
      southern Spain, inland Australia and South Island New Zealand. A detailed
      knowledge of the epidemiology of RHD is essential for the management of the
      disease in natural rabbit populations, either to rebuild or to control
      populations. When RHD first spread among naive wild rabbits, epidemiological
      studies provided unique information on the rate of spread, the possible role of
      insect vectors in transmission, and the correlation between the impact of disease
      on populations and climatic variables. Current research shows a consistent
      pattern of epidemiology between Europe and Australasia. Typically, the most
      severe epizootics of RHD occur among young sub-adult rabbits which have lost age
      related resilience and maternal antibodies. However, the timing of these
      outbreaks reflects climatic variables that determine the breeding season of the
      rabbits and the periods when RHD virus (RDHV) is most likely to persist and
      spread. Further factors that may complicate epidemiology include the possibility
      that non-pathogenic RHDV-like viruses are present in natural rabbit populations.
      Additionally, the question of how the virus persists from year to year remains
      unresolved; persistence in carrier rabbits is a possibility. Understanding of the
      epidemiology of RHD is now sufficiently advanced to consider the possibility of
      manipulating rabbit populations to alter the epidemiological pattern of RHD and
      thereby maximise or minimise the mortality caused by the disease. Altering the
      epidemiology of RHD in this manner would assist the management of wild rabbit
      populations either for conservation or pest control purposes.

PMID- 11974621
TI  - Anthrax and wildlife.
AB  - Although livestock anthrax is declining in many parts of the world, with an
      increasing number of countries probably truly free of the disease, anthrax
      remains enzootic in many national parks and even in some game ranching areas.
      These infected areas can present a persistent risk to surrounding livestock,
      which may otherwise be free of the disease, as well as a public health risk. The
      authors use as examples the national parks in southern Africa, the Wood Buffalo
      National Park in northern Alberta, Canada, and the deer ranching counties in
      south-west Texas, United States of America, to present the range of problems,
      epidemiology, and control procedures. While many advances have been achieved in
      the understanding of this disease, research is required into the genotypic
      grouping of anthrax isolates, improved field diagnostic techniques, and oral
      vaccines, as well as to provide a better understanding of spore survival in soil
      and the ecology of the disease under natural conditions.

PMID- 11974622
TI  - Sarcoptic manage in wildlife.
AB  - Sarcoptic manage caused by Sarcoptes scabiei is responsible for epizootic disease
      in populations of wild canids in North America, Europe and Australia, wild cats
      in Europe and Africa, wild ungulates and wild boars in Europe, wombats and koalas
      in Australia, and great apes and various wild bovids in Africa. Although short
      term mortality may appear devastating, in a self-sustaining population, mortality
      is non-compensatory and a mange epizootic generally does not affect long-term
      population dynamics. Alternatively, the net effect of a mange epizootic can have
      serious consequences in remnant or fragmented populations of CITES-listed,
      threatened, or endangered species where loss of even a few individuals can be
      critical to the survival or restoration of a species (CITES: Convention on
      International Trade in Endangered Species of Wild Fauna and Flora). The
      pathogenesis and concordant clinical symptoms of mange depends on the immune
      status of the respective host. Naive, immunocompromised or anergic animals that
      are unable to evoke hypersensitivity responses develop an extensive epidermal
      hyperkeratosis usually without marked alopecia, but with an underlying chronic
      dermal inflammation and an abundance of mites in the skin. Immunocompetent hosts
      are able to develop strong types I and IV hypersensitivity responses that result
      in a marked decrease and eventual loss of mites in the skin. However, there are
      dramatic structural and functional changes in the skin; it becomes extensively
      thickened, greyish in colour and there is a marked eosinophilia throughout the
      epidermis and dermis. There is often almost complete alopecia. Isolation and
      treatment of infected individuals may be warranted, and has met with some success
      in small remaining populations of certain highly endangered species.

PMID- 11974624
TI  - Bioweapons, bioterrorism and biodiversity: potential impacts of biological
      weapons attacks on agricultural and biological diversity.
AB  - Diseases and biological toxins have been used as weapons of war throughout
      recorded history, from Biblical times through to the present day. Bioweapon uses
      have historically been directed primarily, although not exclusively, against
      human populations. Specialised technicians and state-of-the-art research
      facilities are no longer necessary for the production or deployment of many known
      bioweapon agents and commercially available technologies now permit the large
      scale production of bioweapon agents in small-scale facilities at relatively low
      cost. Failures in the detection and containment of bioweapon and emerging disease
      outbreaks among populations of wildlife and indigenous peoples in developing
      countries could result in severe erosion of genetic diversity in local and
      regional populations of both wild and domestic animals, the extinction of
      endangered species and the extirpation of indigenous peoples and their cultures.
      Our ability to understand and control the spread of diseases within and among
      human and animal populations is increasing but is still insufficient to counter
      the threats presented by existing bioweapon diseases and the growing number of
      highly pathogenic emergent infections. Interdisciplinary and international
      efforts to increase the monitoring, surveillance, identification and reporting of
      disease agents and to better understand the potential dynamics of disease
      transmission within human and animal populations in both industrialised and
      developing country settings will greatly enhance our ability to combat the
      effects of bioweapons and emerging diseases on biological communities and
      biodiversity.

PMID- 11974623
TI  - International regulation of wildlife trade: relevant legislation and
      organisations.
AB  - Trade in wildlife brings into play a variety of legislation from several distinct
      areas of law. Many species of wildlife are subject to restrictions on
      international movement with the aim of protecting wild populations from over
      exploitation. Animal health legislation is strictly applied to the movement of
      most animals to prevent the spread of infectious diseases between importing and
      exporting counties. The welfare of animals in the course of trade requires
      consideration and relevant legislation has been put into place, particularly in
      respect of transportation. A number of institutions have an impact on the trade
      itself or on the legislation that regulates wildlife trade on an international
      basis.

PMID- 11974625
TI  - Emerging infectious diseases in wildlife.
AB  - The processes which give rise to emerging infectious diseases of wildlife can be
      categorised as follows: ecosystem alterations of anthropogenic or natural origin;
      movement of pathogens or vectors, via human or natural agency; and changes in
      microbes or in the recognition of emerging pathogens due to advances in the
      techniques of epidemiology. These are simplistic divisions because factors
      influencing the emergence of diseases of wild animals generally fall into more
      than one category. Mycoplasmosis among passerines is related to habitat changes
      and artificial feeding resulting in increased bird densities and subsequent
      disease transmission. The origin of this strain of Mycoplasma gallisepticum is
      not known. Hantavirus infections in rodents have emerged due to human-induced
      landscape alterations and/or climatic changes influencing population dynamics of
      hantavirus reservoir hosts, with disease consequences for humans. Movement of
      pathogens or vectors is a very important process by which diseases of wildlife
      expand geographic range. Although the origin of caliciviruses of rabbits and
      hares is somewhat obscure, their movement by humans, either deliberately or
      accidentally, has greatly expanded the distribution of these viruses. Rabies is
      an ancient disease, but geographic expansion has occurred by both natural and
      anthropogenic movements of wild animals. Human movement of amphibians may explain
      the distribution of the highly pathogenic chytrid fungus around the world. Newly
      recognised paramyxoviruses may reflect both changes in these pathogens and the
      development of techniques of identification and classification. Many more such
      examples of emerging diseases will arise in the future, given the extensive
      alterations in landscapes world-wide and movements of animals, vectors and
      pathogens. Those who study and diagnose diseases of wildlife must be alert for
      emerging diseases so that the impact of such diseases on wild animals, domestic
      animals and humans can be minimised.

PMID- 11974626
TI  - The value of wildlife.
AB  - The value of wildlife has been widely ignored or under-rated in the past by the
      international community. At most, wildlife was considered from the limited
      aesthetic and touristic aspects. This situation has changed somewhat. In the
      majority of the veterinary profession, which is largely livestock-oriented,
      wildlife is increasingly considered in terms of wild animal production and
      occupies just as relevant a position as domestic animal production. Some
      economists are now trying to quantify the informal nature of a large portion of
      the wildlife sector. The importance of wildlife to local communities is now
      globally recognised in community-based or participatory natural resources
      management programmes. The authors highlight not only the economic importance of
      wildlife (which amounts to billions of United States dollars world-wide), through
      consumptive and non-consumptive uses, but also the present and potential
      nutritional value, the ecological role as well as the socio-cultural significance
      of wildlife for human societies of both the developed and the developing worlds.
      Also addressed in this chapter is a discussion on one of the main threats to
      wildlife conservation which consists of the reduction or even retrieval of the
      different values wildlife can offer.

PMID- 11974627
TI  - Disease management strategies for wildlife.
AB  - Three basic forms of management strategies exist for wildlife disease, as
      follows: prevention of introduction of disease, control of existing disease or
      eradication. Management may be directed at the disease agent, host population,
      habitat or be focused on human activities. Disease agents may be dealt with in
      the environment through disinfection or in the host through treatment.
      Disinfection and pesticides used to destroy agents or vectors are limited to
      local situations, may have serious environmental effects and may result in
      acquired resistance. Difficulty in delivering treatment limits chemotherapy to
      local situations. Host populations may be managed by immunisation, by altering
      their distribution or density, or by extirpation. Immunisation is best suited for
      microparasitic exogenous infections with a low reproductive rate and in
      populations which have a low turnover. Mass immunisation with oral baits has been
      effective, but this strategy is limited to a few serious diseases. It is
      difficult to move wild animals and techniques to discourage animals from entering
      an area become ineffective rapidly. The setting up of fences is feasible only in
      local situations. Selective culling is limited to situations in which affected
      individuals are readily identifiable. General population reduction has had little
      success in disease control but reducing populations surrounding a focus or
      creating a barrier to disease movement have been successful. Population reduction
      is a temporary measure. Eradication of a wildlife population has not been
      attempted for disease management. Habitat modification may be used to reduce
      exposure to disease agents, or to alter host distribution or density. Management
      of diseases of wild animals usually requires a change in human activities. The
      most important method is by restricting translocation of wild animals to prevent
      movement of disease.

PMID- 11974628
TI  - Area-wide biological control of disease vectors and agents affecting wildlife.
AB  - Two examples of area-wide programmes, employing the sterile insect technique
      (SIT), which have eradicated a parasite and a disease vector common to domestic
      and wild animals are described. New World screwworm (NWS), Cochliomyia
      hominivorax, caused significant morbidity and mortality of livestock and wild
      mammals in tropical and subtropical areas of America before eradication was
      achieved in North America using the SIT and other components of an integrated
      pest management (IPM) programme. Movement of wild as well as domestic animals
      from an area which is infested with screwworm to a free area requires
      prophylactic treatment. Tsetse fly-borne trypanosomosis has an immense influence
      on the distribution of people and livestock in Africa. The immunotolerance of
      wildlife to the parasites is an important factor in maintaining some areas
      livestock free as wildlife refuges. Slaughter has ceased of wild hoofstock
      species considered to be disease reservoirs for control purposes. The SIT,
      combined with other IPM measures, has resulted in the eradication of the tsetse
      fly and trypanosomosis from Zanzibar. Other programmes in Africa are underway.
      Microbial 'biopesticides' have also been employed successfully against plant
      insect pests and some vectors of human disease. It seems likely that for the
      immediate future, wildlife may benefit from area-wide biological control
      programmes, intended mainly to protect humans and/or domestic animals.

PMID- 11974629
TI  - Health risk assessment of the translocation of wild animals.
AB  - Potential health risks are always associated with the translocation of wild
      animals. A formal assessment of these health risks should be conducted in advance
      of each translocation, and the results of the risk assessment should be
      incorporated into decisions as to whether or not the translocation should occur
      or whether changes in the translocation protocol could substantially reduce
      health risks inherent in the translocation. Credible health risk assessments can
      be performed by individuals without extensive previous experience, given the
      necessary background in animal health and wildlife biology and access to
      sufficient valid information. Assessment of health risks should not be performed
      or influenced by those who will use the results to make decisions or those with
      vested interests in a particular outcome. The assessment process itself must be
      transparent, and the final risk assessment report must clearly present each step
      taken, all available information and all reasoning. Health risk assessment is a
      rigorous application of common sense to evaluate whether or not important health
      related risks are associated with a proposed activity. The level of health risk
      inherent in a planned translocation is determined by identifying the full range
      of possible health hazards that might be associated with that translocation,
      identifying from among these a subset of potential hazards that require complete
      assessment, and for each hazard thus selected, evaluating the probability that
      the hazardous event will occur and the magnitude of negative consequences if it
      does occur. The combination of probability of occurrence and magnitude of
      consequences constitutes the risk posed by a potential health hazard, and the
      combined risk for each assessed health hazard constitutes the overall health risk
      estimate for the translocation. A valid numerical (quantitative) health risk
      assessment for wild animals is rarely possible because the available information
      on which the assessment must be based is too approximate and imprecise.
      Qualitative health risk assessments for wild animal translocations are usually of
      equal or greater value than numerical assessments and can be of enormous
      importance to wildlife conservation, domestic animal health and public health.

PMID- 11974630
TI  - Infectious animal diseases: the wildlife/livestock interface.
AB  - The long-standing conflict between livestock owners and animal health authorities
      on the one hand, and wildlife conservationists on the other, is largely based on
      differing attitudes to controlling diseases of livestock which are associated
      with wildlife. The authors have attempted to highlight the fact that these
      disease problems are frequently bi-directional at the wildlife/livestock
      interface. The different categories of diseases involved are presented. A new
      dimension being faced by veterinary regulatory authorities is the spectre of
      emerging sylvatic foci of diseases, such as bovine tuberculosis, bovine
      brucellosis and possibly rinderpest; these diseases threaten to undermine
      national and international eradication schemes, which have been implemented and
      executed with significant success, and at great cost. Conversely, wildlife-based
      ecotourism world-wide has expanded rapidly over the past decade and is the source
      of lacking foreign revenue for many developing countries. Traditional subsistence
      farming is still the largest source of much-needed protein on some continents and
      this, together with the growth and hunger of historically disadvantaged
      communities for land, is forcing enterprises and communities with markedly
      different objectives and land-use practices to operate effectively in close
      proximity. Some land-users rely exclusively on wildlife, others on livestock
      and/or agronomy, while yet others need to combine these activities. The net
      result may be an expansion or intensification of the interface between wildlife
      and domestic livestock, which will require innovative control strategies that
      permit differing types of wildlife/livestock interaction, and that do not
      threaten the land-use options of neighbours, or the ability of a country to
      market animals and animal products profitably.

PMID- 11974631
TI  - Surveillance and monitoring of wildlife diseases.
AB  - It is now recognised that those countries which conduct disease surveillance of
      their wild animal populations are more likely to detect the presence of
      infectious and zoonotic diseases and to swiftly adopt counter measures. The
      surveillance and monitoring of disease outbreaks in wildlife populations are
      particularly relevant in these days of rapid human and animal translocation, when
      the contact between wild and domestic animals is close and the threat of a
      bioterrorist attack is very real. The authors describe the problems inherent in
      wildlife disease surveillance and stress the importance of the establishment of
      national strategies for disease detection. The various sampling methods employed
      for monitoring outbreaks of disease and mortality in wildlife populations are
      discussed and their strengths and weaknesses described. A major advantage of an
      efficient disease monitoring programme for wildlife is the early detection of new
      and 'emerging' diseases, some of which may have serious zoonotic and economic
      implications. The authors conclude that wildlife disease monitoring programmes
      that are integrated within national animal health surveillance infrastructures
      should have the capacity to respond promptly to the detection of unusual wildlife
      mortality and to institute epizootiological research into new and emerging
      wildlife diseases.

PMID- 11974632
TI  - Diagnostic pathology of selected diseases in wildlife.
AB  - The prompt detection and effective management of infectious disease in wildlife
      rely greatly on field diagnosis. Although clinical work is sometimes of value,
      the cornerstone of diagnosis is pathological examination (gross necropsy with
      supporting laboratory investigations). The approach and rationale to gross post
      mortem examination are common to all species, despite possible significant
      differences in technique. Likewise, the principles of sampling are usually
      comparable, with emphasis on standardisation, the correct use of equipment, and
      consistency in methods of storage and transportation of specimens. However, the
      type of sample taken and the laboratory tests required differ, depending upon the
      circumstances and possible diagnosis. Retention of material is always important.
      The principles of diagnostic pathology are discussed, with reference to selected
      diseases, namely: mycobacteriosis, Rift Valley fever, rabies, spongiform
      encephalopathies, morbillivirus and poxvirus infections, viral encephalitides,
      West Nile virus infection and chytridiomycosis. The importance of being able to
      perform certain investigations in the field, efficiently and safely, is
      emphasised.

PMID- 11974634
TI  - Family ties extend to patient care at the bedside.

PMID- 11974633
TI  - Geographical information systems as a tool in epidemiological assessment and
      wildlife disease management.
AB  - Geographical information systems (GIS) facilitate the incorporation of spatial
      relationships into epidemiological investigations of wildlife diseases.
      Consisting of data input, management, analysis and presentation components, GIS
      act as an integrative technology in that a range of very varied data sources can
      be combined which describe different aspect of the environment of wild animals.
      The analytical functionality of GIS is still evolving, and ranges from visual to
      exploratory and modelling methods. Output generated by GIS in map format has the
      particular advantage of allowing implicit representation of spatial dependence
      relationships in an intuitive manner. The technology is becoming an essential
      component of modern disease surveillance systems.

PMID- 11974635
TI  - Physician house calls a smart choice for 'frequent fliers'.

PMID- 11974636
TI  - Template for improved management of chronic disease pays off in asthma effort.
AB  - Change is never easy, but the road map developed by Seattle-based Improving
      Chronic Illness Care (ICIC) has helped numerous organizations boost their DM
      outcomes. One of latest organizations to benefit from ICIC's help is Methodist
      Medical Center in Oakridge, TN. See how this organization has applied ICIC's
      Chronic Care Model to its burgeoning asthma population.

PMID- 11974637
TI  - Hospitals boost performance with beta blocker data.

PMID- 11974638
TI  - Do incentives encourage support of clinical quality?
AB  - Do financial incentives for executives of health care delivery systems encourage
      top-down change that supports physicians in making clinical improvements? A new
      survey suggests quality measures have been incorporated into some incentive
      programs, but there's considerable room for improvement.

PMID- 11974639
TI  - Child-adult sexual contact: terminology.

PMID- 11974640
TI  - Sensitivity but not censorship.

PMID- 11974641
TI  - Conscious processing of sexual information: interference caused by sexual primes.
AB  - The concept Sexual Content-Induced Delay (SCID) refers to a hesitancy in decision
      making related to erotic material (Geer & Bellard, 1996; Geer & Melton, 1997).
      Empirical evidence about SCID stems from lexical decision tasks. Our previous
      studies also showed SCID effects in sex versus neutral categorization tasks in
      which pictures were used. In these tasks, recognition of sexual pictures is
      delayed when preceded by consciously presented sexual primes. In the current
      study, 2 manipulations were added to the categorization task to investigate
      underlying information processing mechanisms of SCID. Firstly, the appraisal
      process was influenced by varying the instructions. Secondly, primes with
      nonsexual emotional content were added to test the specificity of the SCID
      effect. Thirty-seven undergraduates were asked to categorize sexual and neutral
      pictures that were primed by sexual, threatening, and neutral primes.
      Participants ignored or focussed prime content dependent on 2 different
      instructions. Results showed that the SCID effect only emerged when sexual primes
      were ignored; however, threatening primes also decelerated recognition of sexual
      pictures after the ignore instruction. Results of the focus instruction were
      qualitatively different, that is, participants recognized sexual pictures faster
      when primed sexually. It was suggested that SCID can be interpreted as the
      activation of regulatory modules by emotional stimuli in the stage of elicitation
      of emotional response. In contrast, when the sexual system is already activated,
      it appears that decisions regarding sexual information are facilitated.

PMID- 11974642
TI  - Predictors of sexual behavior patterns over one year among persons at high risk
      for HIV.
AB  - This study examined the sexual risk act patterns of individuals who participated
      in the NIMH National Multisite HIV Prevention Trial. Patterns of sexual risk were
      examined over 1 year among 3,104 participants from 37 clinics in 7 regional
      sites, within both intervention and control conditions. Four patterns were
      assessed: 100% protected sex or abstinence at follow-up points; improved condom
      use or abstinence, but not completely protected behavior; relapse to unsafe sex;
      and unchanged protection. Participants in the intervention condition who
      responded to the intervention with consistently protected behavior were
      significantly more likely to be older or young adults, recent immigrants to the
      United States, and to not barter sex or have alcohol-related problems. The
      consistently protected participants in the control condition were also
      significantly more likely to be older. The intervention is likely to be
      particularly effective with clients in STD clinics with large immigrant
      populations. Specialized HIV prevention interventions may be needed for
      commercial sex workers, young persons, and those with alcohol-related problems.

PMID- 11974643
TI  - Men who have met sex partners via the Internet: prevalence, predictors, and
      implications for HIV prevention.
AB  - This study examined the prevalence of Internet use for meeting sexual partners
      among men who have sex with men. The study also examined HIV risk behaviors among
      men who reported meeting a sexual partner via the Internet. A sample of 609 men
      was surveyed while attending a gay pride festival in Atlanta, GA. Participants
      completed a questionnaire assessing demographic information, Internet use, gay
      acculturation, AIDS knowledge, attitudes about condoms, global substance use, and
      sexual behavior. A substantial majority of men (75%) reported using the Internet
      to access gay-oriented web sites. One third of the sample (34%) reported having
      met a sexual partner via the Internet. Men meeting sex partners online reported
      higher rates of methamphetamine use. Men meeting sexual partners over the
      Internet reported having sex with more male partners in the previous 6 months (M
      = 8.38, SD = 19.39) compared with men not meeting partners in this manner (M =
      3.13, SD = 4.99, p < .001). Men meeting partners via the Internet also reported
      higher rates of sexual risk behaviors including unprotected anal receptive
      intercourse (p < .05) and unprotected anal insertive intercourse (p < .01). The
      high prevalence of Internet use as a method of meeting sexual partners suggests
      that sexual networks may be forming over the Internet. The Internet therefore
      provides opportunities for new HIV primary prevention interventions.

PMID- 11974644
TI  - Investigating the underlying structure in sadomasochistically oriented behavior.
AB  - This study explores the extent to which 29 individual sexual behaviors,
      previously identified in L. Alison, P. Santtila, N. K. Sandnabba, and N. Nordling
      (2001), as each being associated with 1 of 4 different broad themes of
      sadomasochistically oriented behavior, represent different scales of intensity
      within each theme. The themes were as follows: hypermasculinity, administration
      and receipt of pain, physical restriction, and humiliation. For example, we
      wanted to establish whether skinbranding is a more intense expression of pain
      than spanking; whether faceslapping is a more intense expression of humilitation
      than flagellation, and so on. One hundred and eighty-four participants (22 women
      and 162 men) who were members of two sadomasochistically oriented clubs gave
      information concerning which of the 29 sexual behaviors they had participated in
      during the preceding 12 months. A multivariate analysis (POSAC; Shye, 1994)
      supported the existence of cumulative scales in each of the 4 themes, suggesting
      that the order in which people engage in different sadomasochistic behaviors is
      not random and that specific, less intense behaviors generally precede more
      intense behaviors.

PMID- 11974645
TI  - Reliable and valid self-report outcome measures in sexual (dys)function: a
      systematic review.
AB  - This paper examines the published reliability and validity of non-disease
      specific, self-report measures of sexual function. Relevant papers were found in
      a search of the Embase electronic bibliographic database, for English language
      papers (published 1980-99) reporting on the psychometric testing of sexual
      function questionnaires. Existing published reviews or collections of such
      instruments were also searched, and the reference lists of all papers obtained
      were "back-searched" to identify other measures. Included measures were evaluated
      in a systematic manner using published standards concerning the validity,
      internal consistency, and reproducibility of health measurement scales and
      quality of life measures. Twenty-three self-report measures were identified for
      inclusion in this review. A further 2 measures were identified by reviewers of
      this paper after the main searches were undertaken. One measure was found not to
      be exclusively self-report. Eleven (46% of 24 included measures) did not meet
      minimum published standards for reliability, internal consistency, and validity.
      However one of these was reliable and valid in the female-version only. Of the 14
      reliable and valid measures, or versions thereof (58% of 24), 2 (8% of 24) met
      "superior" psychometric standards. Many measures were developed for use with
      patients in sex or marital therapy, and are mainly suitable for administration to
      people with long-term sex partners. It is sensible to assume that instruments are
      only reliable and valid in the often specialized populations in which they were
      developed.

PMID- 11974646
TI  - Clinical characteristics and treatment response to SSRI in a female pedophile.
AB  - Although much investigation has been done with male sex offenders, there have
      been few studies on female sex offenders. Female sex offenders have been reported
      as having a high incidence of psychiatric disorders, but female paraphilics were
      rarely described. The literature on the treatment of female sex offenders is also
      limited and treatment with a selective serotonin reuptake inhibitor (SSRI) has
      not been reported. This paper presents the case of a woman with DSM-IV
      pedophilia. Her clinical characteristics, her offense history, and her positive
      response to treatment with sertraline (a SSRI) are described. This case adds to
      the limited literature on female pedophiles and suggests that SSRIs may be an
      effective treatment for paraphilic disorders in female sex offenders.

PMID- 11974647
TI  - Pushing for change. Interview by Larry BeSaw.

PMID- 11974648
TI  - Disciplining doctors.

PMID- 11974649
TI  - Fed up!

PMID- 11974650
TI  - Mental health blues.

PMID- 11974651
TI  - Policy canceled.

PMID- 11974652
TI  - Leap or misstep?

PMID- 11974653
TI  - Management of traumatic hyphema in Texas.
AB  - To determine the usual approach to management of traumatic hyphema in Texas, we
      mailed a survey to ophthalmologists in the state who indicated a practice focus
      of either general ophthalmology or pediatric ophthalmology. The survey included
      inquiries regarding type of practice, patient population, frequency of traumatic
      hyphema, laboratory investigations, treatment precautions, medical and surgical
      treatment, criteria for hospitalization, and criteria for surgical intervention.
      Of the 495 surveys mailed out, 169 (response rate = 34.1%) were returned and
      filled out completely. More than half of the respondents do not routinely
      consider sickle cell testing in traumatic hyphema cases. We found no consensus
      regarding use of systemic antifibrinolytic agents, indications for
      hospitalization, or timing of surgical intervention. The results of this survey
      emphasize the lack of consensus surrounding treatment of traumatic hyphema. The
      relative paucity of sickle cell testing among Texas ophthalmologists, however,
      appears inconsistent with recommendations in the medical literature.

PMID- 11974654
TI  - Case management software: how to decide what's right for you.

PMID- 11974655
TI  - Health system designs tool for DRG-specific report.

PMID- 11974656
TI  - ACE unit seeks to reduce elderly functional decline.

PMID- 11974657
TI  - Shortened LOS proves beneficial to teaching.

PMID- 11974658
TI  - Medication errors: what case managers can do. Part 2.

PMID- 11974659
TI  - Finding a compromise between the heart and the brain: strategies for stroke risk
      reduction in coronary artery surgery.

PMID- 11974660
TI  - Magnetocardiography: current status and perspectives. Part II: Clinical
      applications.
AB  - Magnetocardiography (MCG) is a non-invasive and risk-free technique allowing body
      surface recording of the magnetic fields generated by the electrical activity of
      the heart. The MCG recording system allows spatially and temporally accurate
      measurements of the very weak magnetic fields produced by currents flowing within
      myocardial fibers during cardiac activity. MCG has now been around for over 30
      years, but only recently has progress in instrumentation put the technique on the
      verge of clinical applicability. This review summarizes the physical principles,
      instrumentation, main clinical applications and perspectives for the clinical use
      of MCG. This second part is devoted to the description of the main current
      clinical applications and perspectives.

PMID- 11974661
TI  - Prediction of early and delayed postoperative deaths after coronary artery bypass
      surgery alone in Italy. Multivariate predictions based on Cox and logistic models
      and a chart based on the accelerated failure time model.
AB  - BACKGROUND: The aim of the multicenter OP-RISK (OPerative RISK) study was to
      investigate the early (28 days) and delayed (365 days) death rates following
      coronary artery bypass grafting (CABG) among patients representing a nationwide
      distribution [Centers in Northern (2), Central (1) and Southern (1) Italy] and
      further to define the multivariate risk factors for the early and delayed
      mortality after CABG. METHODS: Data were collected from 1126 patients undergoing
      CABG alone. Data were analyzed using Cox and logistic regression models, to
      accurately assess the major factors influencing survival over time after CABG.
      Having defined the significant factors, we constructed a chart of the absolute
      early risk of mortality using the accelerated failure time model. RESULTS: Using
      the Cox proportional hazards model and logistic regression we have demonstrated
      that age, preoperative ejection fraction and heart rate, and the duration of
      aortic cross-clamping are multivariate risk factors in the short and long term.
      The role of one arterial conduit was also assessed. CONCLUSIONS: The OP-RISK
      study produced relevant information for risk assessment and control in CABG and
      the results may form the basis for the objective quality assurance and
      accreditation of cardiac surgical institutions in Italy. Incidentally, Cox model
      appeared more adequate than logistic model for the assessment of the major
      factors influencing survival over time after CABG. The risk factors so assessed
      were used to construct a chart for practical predictive purposes.

PMID- 11974662
TI  - Transcatheter closure of secundum atrial septal defects with the Amplatzer
      occluder in adult patients.
AB  - BACKGROUND: Secundum atrial septal defect (ASD) is a common congenital heart
      disease diagnosed in adulthood. Data regarding the use of the percutaneous
      occluder device in adult populations are very limited and few studies including
      the use of the Amplatzer septal occluder (ASO) device in such populations are
      available. The aim of this study was to evaluAte the immediate and mid-term
      outcomes of the percutaneous ASD closure with the ASO device in an adult
      population. METHODS: Between May 1999 and December 2000, 21 adult patients (8
      males, 13 females) with a mean age of 44.6 +/- 15.1 years were enrolled for an
      attempt at ASD closure with the ASO device. RESULTS: Only 18 of the 21 patients
      underwent implantation of the ASO device, whereas the other 3 patients were
      submitted to cardiac surgery. The ASO device was successfully implanted in 17
      patients (94.4%). The mean maximal ASD transesophageal echocardiography diameter
      was 14.4 +/- 7.2 mm (range 4-23 mm). The mean stretched defect diameter measured
      19.5 +/- 8.4 mm (range 8-34 mm) and the ASO implanted stalk size was 19.8 +/- 8.2
      mm (range 8-34 mm). In 2 (11.1%) of the 18 patients a percutaneous transcatheter
      coronary angioplasty was successfully performed before implantation of the ASO
      device because of coronary artery disease. At 6 months of follow-up,
      transesophageal echo examination showed that the device was correctly positioned
      in all cases. CONCLUSIONS: In adults, transcatheter closure of ASDs with the ASO
      device is a safe and effective alternative to surgical closure. The immediate and
      mid-term outcomes are excellent. However, a combined procedure may be necessary.

PMID- 11974663
TI  - Clinicopathological correlates can predict acute myocarditis in patients with
      recent-onset heart failure: preliminary data.
AB  - BACKGROUND: The aim of this study was to verify whether or not the clinical
      profile could be helpful in diagnosing myocarditis in patients with recent-onset
      (< 6 months) heart failure, suspected myocarditis and a biopsy-proven diagnosis.
      METHODS: From March 1998 to December 2000, 118 patients underwent a complete
      clinical, hemodynamic, echocardiographic and laboratory examination and a
      diagnostic endomyocardial biopsy in our Department; among them, 28 patients were
      admitted with clinically suspected myocarditis; in 9, the diagnosis was confirmed
      by the histopathologic findings. RESULTS: At the time of presentation, patients
      with biopsy-proven myocarditis showed early in-hospital admission (median 6 vs 69
      days) with fever, a higher sinus rate and a significantly lower systolic blood
      pressure. Left ventricular dilation was observed in the non-myocarditis group
      only (left ventricular end-diastolic diameter 65.0 +/- 8.9 vs 52.6 +/- 5.8 mm);
      right ventricular function, as assessed by evaluation of the tricuspid annulus
      plane systolic excursion (TAPSE) and the right ventricular ejection fraction
      (RVEF) were found to be significantly lower in the myocarditis group (TAPSE 14.2
      +/- 3.6 vs 20.3 +/- 7.0 mm; RVEF 21.3 +/- 11.1 vs 30.3 +/- 11.5%). Only patients
      with biopsy-proven myocarditis had an increase in serum creatine kinase and
      inflammatory markers (erythrocyte sedimentation rate and white blood cell count).
      Three cases had a clinical presentation of fulminant myocarditis showing marked
      increases in the serum levels of creatine kinase and inflammatory markers, and
      severely compromised right ventricular function and cardiac index. CONCLUSIONS:
      At univariate analysis, an early onset, fever, tachycardia, hypotension, a
      reduced right ventricular function, increased creatine kinase, erythrocyte
      sedimentation rate and white blood cell count were predictive of myocarditis. In
      patients with recent-onset heart failure, the clinical, laboratory and
      echocardiographic profiles can suggest, but not prove, a diagnosis of
      myocarditis.

PMID- 11974664
TI  - Prognostic value of iron, nutritional status indexes and acute phase protein in
      acute coronary syndromes.
AB  - BACKGROUND: The relation between the inflammatory status during unstable angina
      and nutritional parameters has not been well described. We sought to investigate
      the relation between the acute inflammatory status, as evaluated on the basis of
      high C-reactive protein (CRP) and serum amyloid A levels and laboratory indexes
      of iron and nutritional status in patients with unstable angina, and whether the
      variations in iron levels have a prognostic significance. METHODS: The study
      population consisted of 98 patients admitted to our facility with unstable (group
      1: 64 consecutive patients, 52 males, 12 females, mean age 66 +/- 10 years) or
      stable angina (group 2: 34 patients, 30 males, 4 females, mean age 65 +/- 9
      years). The hemoglobin levels, the erythrocyte mean cell volume, serum iron
      levels, the increase in transferrin levels, the decrease in the percent
      transferrin saturation, ferritin levels, the nutritional status, and the CRP and
      serum amyloid A levels were measured. RESULTS: On the basis of a CRP value > 1
      mg/dl, 47 patients with unstable angina and 4 patients with stable angina were
      identified as having active inflammatory disease. The presence of inflammation
      was associated with significantly lower mean values of hemoglobin, erythrocyte
      mean cell volume, serum iron and transferrin levels, and percent transferrin
      saturation in comparison with patients without inflammation. A significant
      inverse correlation coefficient between a CRP level > 1 mg/dl and hemoglobin,
      transferrin levels and percent transferrin saturation was observed: the strongest
      correlation was with serum iron levels. The relative risk of total cardiac events
      was significantly greater in patients with low serum iron levels than in those
      with high serum iron levels. CONCLUSIONS: Patients with acute inflammation
      present altered iron status indexes. Increased CRP levels and reduced serum iron
      levels are associated with a worse outcome in patients with unstable angina.

PMID- 11974665
TI  - Silent embolism of a large pedunculated left atrial thrombus.
AB  - Patients with a left atrial thrombus are considered as being at high risk for
      thromboembolic events. Although embolization may be asymptomatic, embolic events
      related to large thrombi are usually clinically manifest and tend to be
      associated with a worse prognosis. We describe the very unusual case of a patient
      with atrial fibrillation in whom two-dimensional echocardiography revealed a
      large, pedunculated, highly mobile left atrial thrombus attached by a thin stalk
      to the interatrial septum. Because of the high risk of embolism the patient was
      submitted to urgent surgery. At surgery, only the stalk was found. No mass was
      visualized at intraoperative transesophageal echocardiography. The patient had an
      uneventful postoperative course without signs of embolism. Computed tomography of
      the brain did not reveal any cerebral infarction.

PMID- 11974666
TI  - Coronary artery aneurysm after stent implantation: acute and long-term results
      after percutaneous treatment with a stent graft.
AB  - A patient with unstable angina was treated with elective Palmaz-Schatz stent
      implantation on a focal stenosis of the left circumflex artery. One year later, a
      large (13 mm in diameter) coronary artery aneurysm was diagnosed at angiography
      in the stented site. Intravascular ultrasound examination confirmed the presence
      of a true aneurysm located at the proximal end of the stent. The aneurysm was
      successfully treated with a Jostent Graft (Jomed Implantate) consisting of two
      slotted tube stainless steel stents supporting a polytetrafluoroethylene tube.
      The stent graft was implanted under intravascular ultrasound guidance. The 18
      month angiographic follow-up showed good patency of the stent graft and complete
      exclusion of the aneurysm.

PMID- 11974668
TI  - Evidence of a concealed accessory pathway during a tachycardia with three QRS
      morphologies and cycle length variations related to functional bundle branch
      block.

PMID- 11974667
TI  - Significance of ST-segment depression during supraventricular tachycardia. Clues
      offered by its return to normal at the end of the episode.
AB  - The finding of transient ST-segment depression during episodes of
      supraventricular tachycardia is common but its ischemic significance is usually
      uncertain. Several authors came to the conclusion that in the absence of positive
      myocardial scintigraphy these alterations are not associated with a coronary flow
      limiting stenosis. Our report tends to confirm this view but we suggest to
      observe the evolution of ST-segment changes at the very end of the episodes;
      these mechanisms have not been adequately addressed in previous studies and could
      provide useful clues to the ischemic or non-ischemic origin of ST-segment
      abnormalities.

PMID- 11974669
TI  - Subacute ventricular wall rupture.

PMID- 11974670
TI  - Pharmacogenetics: has it reached the clinic?
AB  - Genetic variation in drug-metabolizing enzymes contributes to the variability in
      drug responses seen in humans. Information in the area is expanding rapidly, and
      the clinical significance of many of the polymorphisms is only now being
      elucidated. It is clear that polymorphism frequency varies markedly by race and
      ethnicity, but major differences by sex have not been reported. Screening for
      genetic variation in most drug-metabolizing enzymes is not recommended; the very
      important exception is the need to determine the thiopurine transferase activity
      of patients who may receive thiopurines (e.g., 6-mercaptopurine and azathioprine)
      because clinically life-threatening complications or decreased efficacy is
      strongly related to the genetically determined activity of this enzyme.

PMID- 11974671
TI  - Periodicity of noncontact anterior cruciate ligament injuries during the
      menstrual cycle.
AB  - BACKGROUND: Approximately 80,000 anterior cruciate ligament (ACL) tears occur per
      year in the United States. The majority of all ACL injuries are thought to be
      noncontact in nature with no clear mechanism of injury present. The increased
      rate of noncontact ACL injury in female athletes as compared to male athletes in
      some sports is well-documented. It explains an interest in the biochemical
      components as a predisposition to sustain an injury. OBJECTIVE: The goal of this
      study was to analyze the 28-day periodicity of noncontact ACL injuries in female
      athletes taking and not taking oral contraceptives (OCs). DESIGN: From 1996 to
      1999, a descriptive project in the National Collegiate Athletic Association and
      National Association of Intercollegiate Athletics member schools allowed for an
      assessment of the commonality in the characteristics of the noncontact-ACL
      injured athletes. SUBJECTS: Of the 128 female athletes, 83 satisfied the study
      inclusion criteria. Twenty-five of the subjects represented the "On-Pills"
      subgroup and 58 of them represented the "Off-Pills" subgroup. METHODS: The data
      were collected directly from the athletes by the certified athletic trainer at
      the school. STATISTICAL ANALYSIS: Centered moving average with a span of four
      days as well as linear and nonlinear regression were used to analyze the data.
      RESULTS: A significant 28-day periodicity of injuries was present in the entire
      population as well as in the two subgroups. High- and low-risk time intervals
      were associated primarily with follicular and luteal phases. There was a
      significant difference in the time dependency of the number of injuries between
      the two subgroups: female athletes taking OCs demonstrated a greater difference
      between high and low risks, with a high-risk period shifted toward the beginning
      of the cycle. CONCLUSION: There is a significant relationship between the
      occurrence of a noncontact ACL injury and the collegiate athlete's menstrual
      cycle regardless of oral contraceptive use status.

PMID- 11974672
TI  - The Framingham Study: historical insight on the impact of cardiovascular risk
      factors in men versus women.
AB  - The Framingham Study has investigated the evolution of cardiovascular disease
      (CVD) over five decades in a general population sample of men and women. This
      study has provided valuable insight into the prevalence, incidence, prognosis,
      and predisposing risk factors for CVD in women compared to men. Women were found
      to outlive men and to experience fewer atherosclerotic CVD events, lagging behind
      men in incidence by 10-20 years. However, this gap in incidence closed with
      advancing age and in the elderly, CVD became the leading cause of death in women
      as well as men. Comparing the life-time risk of coronary heart disease (CHD) with
      that of breast cancer in the Framingham cohort indicated a threefold greater
      chance of having a CHD event (24-32%) than breast cancer (7-12.5%). Thus, CVD is
      not a minor problem in women, and vigorous preventive measures are warranted at
      all ages. There is a need for particular attention to glucose intolerance,
      abdominal obesity, and blood lipids, and a need for a great sense of urgency when
      hypertension is associated with diabetes or promotes left ventricular
      hypertrophy.

PMID- 11974673
TI  - Social and economic causes of depression.
AB  - Depression is a serious problem for women, one that is, in some cases, related to
      the sociocultural environment. This article posits that events and processes in
      the environment can interfere with an individual's effort to fulfill life goals,
      thereby creating the potential for depression. Both the number and the character
      of these disruptive events and processes contribute to the likelihood of
      developing illness. Women with high numbers of events that are characterized by
      humiliation, entrapment, and bereavement, for example, will be at high risk for
      depression. The psychosocial management of the environmental contribution to
      depression is explored.

PMID- 11974674
TI  - Gender differences in fibromyalgia and other related syndromes.
AB  - Fibromyalgia syndrome is characterized by widespread musculoskeletal pain,
      fatigue, poor sleep, and tenderness on palpation at multiple sites called tender
      points. It occurs mostly among women; only about 10% of patients are men. Two
      recent studies showed that women had significantly more common fatigue, morning
      fatigue, "hurt all over," a greater total number of symptoms, as well as a
      greater number of tender points. Gender differences have also been reported in
      other related syndromes such as tension headache, migraine, irritable bowel
      syndrome, chronic fatigue syndrome, and temporomandibular disorder. Although the
      mechanisms of gender differences in these illnesses are not fully understood,
      they are likely to involve an interaction between biology, psychology, and
      sociocultural factors.

PMID- 11974675
TI  - Effects of race, ethnicity, gender, culture, literacy, and social marketing on
      public health.
AB  - Societies globally have a long road ahead in eliminating health risks and
      discrepancies due to race and ethnicity, gender, culture, and illiteracy. In
      terms of race, for example, females and African-Americans are less likely to be
      referred for cardiac catheterization, and Caucasians are more likely than
      minorities to receive pain management in the emergency room. Regarding gender,
      physiologic differences certainly account for some divergent health outcomes, but
      they do not explain how women and men have different prevalences of diseases that
      are not obviously gender-specific. Cultural beliefs play a vital role in
      determining health choices, and health care professionals need a deeper
      understanding of these beliefs prior to promoting certain health interventions.
      Illiteracy may also prevent a person from following health instructions, and the
      strong association between illiteracy and poverty may exert powerful, negative
      influences on health outcomes. Employing the characteristics of social marketing
      (synchronous messages, reinforcement, and actionability) may help society to
      overcome some of the obstacles.

PMID- 11974676
TI  - Younger women more likely than men to die after bypass surgery.

PMID- 11974677
TI  - Are men in danger of extinction?

PMID- 11974678
TI  - FDA approves NuvaRing contraceptive implant.

PMID- 11974679
TI  - New COX-2 arthritis drug receives FDA approval.

PMID- 11974680
TI  - Postpartum depression and gender-specific justice.

PMID- 11974681
TI  - Barriers to health and wellness from a disability perspective.

PMID- 11974682
TI  - [Will your patient tolerate anesthesia? Assessment in general practice].

PMID- 11974683
TI  - [No findings--but the patient feels chronically ill. How to heal the
      hypochondriac? (interview by Dr. med. Julia Rautenstrauch)].

PMID- 11974684
TI  - [Skin changes of the penis. Differentiation between local findings and systemic
      diseases!].
AB  - In the event of diseases affecting the penis, both patient and doctor may first
      have to overcome a certain "threshold of inhibition". Since, however, the
      clinical examination of the genitals is uncomplicated and informative, the
      general practitioner should be familiar with the major pathological conditions
      that may affect the male organ. Diseases of the penis can take the form of a
      local condition or be part of a generalized cutaneous disease. Examples of the
      latter that frequently involve the penis are psoriasis and lichen planus.
      Infections are caused by bacteria, fungi, viruses or parasites, and Candida,
      streptococci and anaerobes need particular mention. Other major differential
      diagnoses are cutaneous drug reactions, contact dermatitis and neoplastic
      lesions. But, excessive hygiene may also cause problems ("over-treatment
      balanitis").

PMID- 11974685
TI  - [Chlamydia, herpes, chancre,gonorrhea, syphilis. Are you familiar with the
      therapy?].
AB  - Sexually transmitted diseases (STDs) which today are taken to cover all genital
      contact infections including the classical venereal diseases, have increased
      appreciably in recent years. With regard to the penis, STDs may manifest as
      papules, pustules and ulcers including urethral discharge and swelling of
      regional lymph nodes. Possible causes may be bacterial, viral or fungal.
      Depending on the pathogens involved, local or hematogeneous dissemination may
      occur. Treatment of infectious penile diseases follows the recommendations
      contained in the guidelines of the German Society for STD.

PMID- 11974686
TI  - [Induratio penis plastica. Soft roentgen rays can ameliorate pain during
      intercourse].

PMID- 11974688
TI  - [Diabetic foot syndrome. Foot education and foot care].

PMID- 11974687
TI  - [Acute fever in the infant and young child. Every age group requires a different
      approach!].

PMID- 11974689
TI  - [2 days after a long care trip. Suddenly the left arm was limp].

PMID- 11974690
TI  - [Mandatory health insurance figures are in the red. And we should tighten our
      belts].

PMID- 11974691
TI  - [The difficult road to COPD diagnosis. Often innocent hearts are suspected].

PMID- 11974693
TI  - [Modern asthma management. Getting a grip on the illness].

PMID- 11974692
TI  - [Asthma as social disease. Effective control is possible!].

PMID- 11974694
TI  - [Shock reaction caused by tablet color additive. Expert recommend: no generics
      for allergic patients].

PMID- 11974695
TI  - Staying power. A nurse is leading the campaign to save services at her local
      hospitals.

PMID- 11974696
TI  - Does it all add up?

PMID- 11974697
TI  - Anything but magnolia.

PMID- 11974698
TI  - Country strife.

PMID- 11974699
TI  - Sigh of relief.

PMID- 11974701
TI  - NHS already has a tight rein on community care.

PMID- 11974700
TI  - Driven out by racism.

PMID- 11974702
TI  - Advanced nursing practice.
AB  - BACKGROUND: Mark Carroll examines the concept of advanced nursing practice and
      highlights a number of the difficulties in assessing and defining different
      levels of practice. Some of the differences and similarities between advanced
      practice in the US and UK are compared and contrasted. CONCLUSION: Issues of
      elitism and the lack of correlation between the needs of the healthcare system
      and professional self-interest prevent the advancement of specialist roles in the
      UK. The continuing focus of local trusts on the medicalisation of roles to meet
      the demands of the healthcare system appears to ignore the need for nursing to
      expand from within the profession.

PMID- 11974703
TI  - Developing leadership through action learning.
AB  - The authors discuss the use of action learning to help nurses based at Guy's and
      St Thomas' Hospital Trust develop clinical leadership skills.

PMID- 11974704
TI  - Racism in NHS is driving out ethnic minority nurses.

PMID- 11974705
TI  - Immunisation information for parents.
AB  - Many infectious diseases have been nearly eliminated in industrialised countries
      through mass vaccination programmes. However, the bacteria and viruses that cause
      these diseases still exist and are a threat to the health of those who are not
      protected through vaccination. The authors examine the benefits of childhood
      immunisation and this information could be used by nurses when advising parents.

PMID- 11974707
TI  - Three overcrowded A&E units 'compromise safety'.

PMID- 11974706
TI  - Rehabilitation following stroke.
AB  - Rehabilitation following stroke begins as soon as the patient is medically stable
      and continues after discharge from hospital. This article describes the processes
      involved.

PMID- 11974708
TI  - Poor quality of elderly care deterring students.

PMID- 11974709
TI  - Nurse clinics suit arthritis patients.

PMID- 11974710
TI  - Nurses say: it's time to strike.

PMID- 11974711
TI  - Drugs/alcohol rehabilitation. Top care without the judgement.

PMID- 11974712
TI  - Divided we fall.

PMID- 11974713
TI  - Do shock tactics help to combat drug misuse?

PMID- 11974720
TI  - Modern matrons make their mark.

PMID- 11974721
TI  - A ginger nibble a day keeps queasiness at bay.

PMID- 11974722
TI  - Last impressions.

PMID- 11974723
TI  - Seen but not heard.

PMID- 11974724
TI  - Reflective, holistic care after radical penectomy.
AB  - This case study describes the management of a patient with complex problems by a
      urology nurse specialist. Penile amputation and the creation of a colostomy had a
      severe impact on body image so the patient's care required a holistic approach.
      He also needed the support of community nurses, and collaboration between them
      and the urology nurse specialist prevented fragmentation of his care in the end
      stages of his life.

PMID- 11974725
TI  - Terminal illness and body image.
AB  - Mark Wareing's case study of a patient with penile cancer (p34) offers an insight
      into issues of disturbed body image at the end of life. This paper explores some
      of the patient's experiences in terms of the confrontation and avoidance of
      difficulties after disfigurement. The effect of the nurse's own anxieties when
      reflecting on the patient's experiences is also discussed.

PMID- 11974726
TI  - Caseload management in learning disabilities.
AB  - Like most health and social services, community learning disability teams are
      under increasing pressure to manage burgeoning caseloads without extra resources,
      both in terms of finances and staffing. This paper describes how one team set out
      to help practitioners manage their caseloads by developing tools to standardise
      workloads and prioritize referrals according to client need.

PMID- 11974727
TI  - Nursing with dignity. Part 6: Sikhism.
AB  - This article describes the main teachings and customs of Sikhism. It offers some
      guidelines to enable nurses to provide sensitive and appropriate nursing care to
      Sikh patients.

PMID- 11974730
TI  - The nurse's role in bowel awareness.
AB  - Promoting good health and preventing ill health are part of the nurse's role, and
      using a model for health promotion in the colorectal nursing service is an
      effective way to improve patient care. This article considers referral guidelines
      for patients with suspected colorectal cancer and suggests methods of raising
      public awareness.

PMID- 11974731
TI  - Day surgery: an exciting new career pathway.
AB  - It could be argued that day surgery is seen as a poor relation to more exciting
      specialties, but the health secretary's campaign to expand day surgery has
      signalled a sea change in approach. A wide variety of procedures can be carried
      out in a day-surgery unit and nursing involvement is crucial. With the scope of
      day surgery increasing, it offers exciting opportunities and expanded roles for
      nurses.

PMID- 11974732
TI  - Cardiopulmonary resuscitation. Bag/valve/mask ventilation.

PMID- 11974734
TI  - The extended formulary and wound care.

PMID- 11974735
TI  - Can tap water be used to irrigate wounds in A&E?
AB  - After critiquing the seven selected articles, it seems likely that tap water can
      be used as an irrigant and cleansing agent for soft-tissue wounds. However, the
      current research on tap water has involved human and rat wound studies and tap
      water culture studies (Dire, 1990; Riyat and Quinton, 1997; Moscati, 1998). The
      research is strong, but limitations in current research remain an issue for
      practice (Towler, 2000). The use of tap water is a cost and practicality issue,
      and changing current practice is always difficult, as it would seem that the use
      normal saline is more of a ritualistic process rather than one based on hard
      evidence (Glover, 1999). Two key conclusions could be drawn from the available
      research: The tap water tested was generally agreed to be safe from harmful
      bacteria and had no contaminating bacteria; Human and rat models showed a clear
      benefit in using tap water to cleanse soft tissue wounds, thus concluding tap
      water is safe for use on wounds (Towler, 2000). The financial benefits were also
      stated in the studies; tap water can have huge cost-saving potential for A&E
      departments. In an increasingly cost-conscious NHS this could be a major driving
      factor for changing practice. However, there were limitations in the
      methodologies of the selected articles in this critique. Most of the studies
      measured wound infection rates, but the various researchers did not take into
      account other factors affecting the likelihood of infection rates and wound
      progress which would ultimately affect wound infection rates by killing any
      bacteria in vivo.

PMID- 11974746
TI  - Meet the man with the plan. Interview by Adrian O'Dowd.

PMID- 11974739
TI  - Patient compliance and chronic wounds.

PMID- 11974747
TI  - Naval nursing. The shipping news.

PMID- 11974748
TI  - Foreign nurses. Pooh-poohing the language test.

PMID- 11974749
TI  - Should the organ donation consent laws be overhauled?

PMID- 11974751
TI  - People of faith, I don't believe it.

PMID- 11974753
TI  - Contact is the key.

PMID- 11974752
TI  - Have you got a life?

PMID- 11974754
TI  - We bought our own GP.

PMID- 11974755
TI  - Diary of a nurse with cancer. Rising from the ashes.

PMID- 11974757
TI  - We need nurses to rule the roost.

PMID- 11974759
TI  - Pressure-ulcer prevention. Part 3. Prevention strategies.

PMID- 11974758
TI  - Rheumatoid arthritis: limiting the damage.

PMID- 11974763
TI  - Nursing with dignity. Part 5: Rastafarianism.

PMID- 11974764
TI  - Cardiopulmonary resuscitation. Mouth-to-mask ventilation.

PMID- 11974774
TI  - Reluctant prescribers.

PMID- 11974775
TI  - Anthrax the facts.

PMID- 11974776
TI  - Searching for a role.

PMID- 11974777
TI  - HIV in India. Interview by Mary Hampshire.

PMID- 11974778
TI  - Save the children.

PMID- 11974779
TI  - Private grief.

PMID- 11974780
TI  - 18. Wound assessment. Removal of skin closures.

PMID- 11974782
TI  - Do we need another model for mental health care?
AB  - In this discussion, James Noak critiques Fletcher and Stevenson's (2001) article
      'Launching the Tidal Model in an adult mental health programme'. Responses from
      the authors and Phil Barker, author of the Tidal Model, follow.

PMID- 11974783
TI  - Career pathways in research: pharmaceutical.
AB  - The pharmaceutical pathway is the final article in this series on career pathways
      and highlights opportunities for nurses within associated industries. This
      pathway shows that nurses can use their nursing qualifications, combined with
      their knowledge, skills and expertise, to develop a career within another sphere
      of employment.

PMID- 11974784
TI  - The nurse's role in managing constipation.
AB  - Constipation is a problem that affects patients in many care settings. Although
      recommendations are made for specific groups of patients with constipation, such
      as older patients and children, there is less information available for general
      adult patients. Angela Day discusses the need for clinical audit to ensure that
      nurses are using the most effective options for managing and preventing
      constipation, and examines the treatment options currently available.

PMID- 11974785
TI  - Integrated continence services.
AB  - Nurses have an important role in continence promotion. Deborah Rigby argues that
      effective continence care should be multidisciplinary and seamless, from the
      patient's home through primary care and local community services to secondary
      hospital services.

PMID- 11974788
TI  - Flesh on the bones.

PMID- 11974789
TI  - Keeping up appearances.

PMID- 11974792
TI  - Strength in numbers.

PMID- 11974793
TI  - Going their own way.

PMID- 11974794
TI  - Exercising choice.

PMID- 11974795
TI  - Crossborder care. Interview by Alison Moore.

PMID- 11974796
TI  - Foreign aid.

PMID- 11974797
TI  - Don't get specific.

PMID- 11974798
TI  - Face to face with politicians.

PMID- 11974799
TI  - If the figures fit....

PMID- 11974800
TI  - Goodbye sweetheart....

PMID- 11974805
TI  - Nurses' experiences of working with trauma patients.
AB  - AIM: To identify the issues relating to nursing care of trauma patients at St
      George Hospital in Sydney, Australia. METHOD: A series of nursing focus groups
      were conducted with nurses from the emergency department, high dependency
      surgical ward and several general surgical wards. The nurses were asked seven
      questions relating to their experience of working with trauma patients. RESULTS:
      The resulting data identified recurring themes, such as communication, education,
      documentation, pain management, workload and resources. CONCLUSION: It is hoped
      that the information from the focus groups will lead to an improvement in the
      communication between healthcare professionals as well as better co-ordination of
      patient care.

PMID- 11974808
TI  - Nursing cadet courses.
AB  - This article outlines the model formulated to develop a cadet scheme in a
      collaborative partnership between Leicestershire NHS Trusts, De Montfort
      University School of Nursing and Midwifery, Leicester, and Lincolnshire and
      Leicestershire Education Consortia.

PMID- 11974809
TI  - Establishing an in-house journal.
AB  - Articles in journals such as Nursing Standard offer nurses a valuable means to
      keep their knowledge updated, but how many people do you know who have written an
      article? The majority of research undertaken by nurses remains unpublished
      (Humphris 1999), so much potentially useful experience, knowledge, ideas and
      research are lost. This article describes how the School of Health, Biological
      and Environmental Sciences (HeBES) at Middlesex University established an in
      house journal to encourage nurses to develop their skills of writing for
      publication.

PMID- 11974810
TI  - Prevention and management of pneumococcal disease.
AB  - Pneumococcal pneumonia is associated with high mortality in immunocompromised and
      older people. The authors discuss the role nurses have in increasing awareness of
      vaccination and use of preventive interventions to target at-risk patients.

PMID- 11974820
TI  - Invaluable assistance.

PMID- 11974821
TI  - Need to know basis.

PMID- 11974822
TI  - Changing lives. Interview by Colin Parish.

PMID- 11974823
TI  - Mother courage. Interview by Mary Hampshire.

PMID- 11974825
TI  - Patient group directions in nurse-led sexual health clinics.
AB  - BACKGROUND: This article details an audit of the supply of medications by
      specialist nurses at a genitourinary medicine clinic. CONCLUSION: The use of
      patient group directions resulted in a reduced number of prescriptions being
      required from doctors, thus saving time for them, the nurses and patients.

PMID- 11974826
TI  - Best practice in vaccine administration.
AB  - Good practice is essential for nurses working in the field of vaccine
      administration to ensure that patients receive the best care possible. This
      article discusses the results of a survey of 500 practice nurses to assess
      knowledge of best practice in vaccine administration. As a result, a task force
      of expert nurses and doctors was convened to develop guidance on best practice in
      this area.

PMID- 11974829
TI  - Career pathways in research: academic.
AB  - The academic pathway is the fourth in this series on career pathways and might be
      considered the most traditional career related to research. However, as is
      demonstrated in this series, research is every nurse's business and not a
      discipline to be conducted solely through academic institutions.

PMID- 11974830
TI  - Meningococcal infection.
AB  - Meningococcal disease is an important medical emergency demanding early diagnosis
      and prompt treatment. This article provides an overview of meningococcal
      infection and discusses mode of transmission, risk factors, prevention of spread,
      vaccination and current recommendations for treatment.

PMID- 11974839
TI  - Shifting position.

PMID- 11974840
TI  - Research fraud squad.

PMID- 11974841
TI  - Splendid isolation. Interview by Steven Black.

PMID- 11974842
TI  - Causing a stir.

PMID- 11974843
TI  - No place like home. Interview by Judy Czylok.

PMID- 11974844
TI  - Keep in touch. How would you cope if your patient was deaf and blind?

PMID- 11974845
TI  - I reflect, therefore I am.

PMID- 11974846
TI  - See you in court.

PMID- 11974848
TI  - How can the uptake of cervical cytology screening be improved?
AB  - BACKGROUND: Cervical cancer remains a killer, despite a screening programme
      designed to detect cases in the early stages of development. A number of factors
      appear to influence a woman's decision to attend for a smear test. This
      literature review considers these factors, and whether nurses can play a part in
      reducing the death rate by dispelling the misapprehensions and misinformation
      that deter vulnerable women from attending. CONCLUSION: There is a great need for
      modification and improvement of the present screening programme if all women who
      are at risk from cervical cancer are to be encouraged to attend for screening.
      The attitude of those who conduct smear tests is often crucial in gaining women's
      confidence--an unpleasant experience might deter a patient from attending again.
      Other barriers to attendance include administrative errors and lack of knowledge.
      Given the impact of mass advertising and health promotion campaigns in other
      areas, such as smoking cessation, there is clearly a need for a similar strategy
      to be applied to cervical screening.

PMID- 11974849
TI  - Preparing nurse managers to mentor students.
AB  - AIM: To explore clinical nurse managers' perceptions of factors influencing their
      ability to perform their clinical leadership role. METHOD: A random sample of 15
      clinical nurse managers in four acute NHS trusts was interviewed in depth to
      identify and explore factors that they perceived to be helping or hindering their
      performance. The qualitative data were analysed to identify recurrent themes,
      which were used to develop a survey questionnaire that was distributed to the
      remaining clinical nurse managers in the four trusts (n = 152). RESULTS: The
      response rate was 65 per cent (n = 99). Many of the clinical nurse managers
      reported poor preparation to undertake key aspects of their role and did not
      favour open learning as a method of continuing professional development.
      CONCLUSION: The findings are of interest in the context of the new framework
      proposed by the English National Board (ENB) and the Department of Health for the
      preparation of nurse educators. Many of the findings are identical to the
      advisory standards set out for mentors in Preparation of Mentors and Teachers: A
      New Framework of Guidance (ENB and DoH 2001a). Attention to the development of
      clinical nurse managers, as well as new mentors, should continue to ensure that
      the proposed changes meet the needs of both groups.

PMID- 11974850
TI  - The management of minor burns and scalds in children.
AB  - When nursing children with minor burns and scalds, it is essential to have a
      thorough understanding of the skin and the way it reacts to thermal injury. This
      article explains the processes involved and advises on dealing with injured
      children and their parents.

PMID- 11974853
TI  - [Structural basis for the molecular switching in regulatory mechanism of muscle
      contraction].

PMID- 11974854
TI  - [Regulation of stress-activated protein kinase signaling pathways by protein
      phosphatases].

PMID- 11974855
TI  - [Root pattern formation and intercellular signal transduction].

PMID- 11974856
TI  - [Plant in vitro transcription systems].

PMID- 11974857
TI  - [Resolved structure-function of a K channel: surprising but beautiful
      conclusions].

PMID- 11974858
TI  - [Creative biochemists--Peter Mitchell].

PMID- 11974859
TI  - [Crystal structure of phoborhodopsin: mechanisms of color tuning and signal
      transduction].

PMID- 11974860
TI  - [Protein chip, an innovative high throughput method for detection of functional
      proteins].

PMID- 11974861
TI  - [UNIX environment for bioinformatics in wet laboratory].

PMID- 11974862
TI  - [Mastering Web-based analysis of gene networks].

PMID- 11974863
TI  - [The factors determining diagnostic accuracy in CT-guided percutaneous needle
      biopsy of small pulmonary nodules].
AB  - Between February 1997 and March 1999, 79 consecutive CT-guided automated needle
      biopsy procedures were performed in 78 patients (79 small pulmonary nodules
      measuring 20 mm or less in diameter). In 69 (87%) of 79 lesions, sufficient
      material for histologic diagnosis was obtained. We evaluated the factors
      affecting diagnostic accuracy in CT-guided automated needle biopsy. Lesion
      diameter, depth from skin, chronic pulmonary disease and location were analyzed.
      The diameter of the lesion was a significant factor contributing to diagnostic
      accuracy (p = 0.0108). Pneumothorax occurred in 18 cases (23%). In 5 cases (6%),
      chest tube placement was necessary. Postbiopsy hemoptysis or hemosputum occurred
      in 23 cases (29%). In conclusion, lesion diameter was a critical factor in
      diagnostic accuracy. CT-guided automated needle biopsy is a feasible, useful and
      safe technique for the histological diagnosis of small lung lesions, but
      especially those larger than 8 mm in diameter.

PMID- 11974864
TI  - [Tumor markers in pleural effusion of patients with lung cancer and patients with
      tuberculous pleurisy].
AB  - Carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), NCC-ST-439,
      carbohydrate antigen 19-9 (CA 19-9), cytokeratin 19 fragment (CYFRA 21-1), sialyl
      Lewis X-i antigen (SLX), progastrin-releasing peptide (ProGRP), squamous cell
      carcinoma antigen (SCC) and neuron specific enolase (NSE) were evaluated in the
      pleural effusion of 39 patients with lung cancer (29 adenocarcinomas, seven small
      cell carcinomas, three squamous cell carcinomas) and 43 patients with tuberculous
      pleurisy. The levels of the tumor markers other than SCC and NSE were
      significantly higher in lung cancer than in tuberculosis. High levels of CYFRA 21
      1 and SCC were observed in squamous cell carcinoma and high levels of ProGRP and
      NSE were observed in small-cell carcinoma. According to the validity score,
      sensitivity (%) + specificity (%) - 100, the optimal cut-off levels of pleural
      effusion were 8.1 ng/ml for CEA, 660 U/ml for CA 125, 2.6 U/ml for NCC-ST-439, 10
      U/ml for CA 19-9, 65 ng/ml for CYFRA 21-1, 140 U/ml for SLX, 23.2 pg/ml for
      ProGRP, 0.6 ng/ml for SCC and 5 ng/ml for NSE. By comparison of validity scores
      for each optimal cut-off level and of receiver operating characteristic (ROC)
      curves, we suggest that a CEA assay is the most useful for pleural effusion. The
      combined assay of CEA + ProGRP and CEA + ProGRP + CYFRA 21-1 were considered to
      be useful.

PMID- 11974865
TI  - [Chronic obstructive pulmonary disease (COPD) in the elderly: analysis from
      questionnaire about attitudes to the COPD guideline of the Japanese Respiratory
      Society and actual therapy for COPD used by physicians].
AB  - We have conducted a survey of attitudes to chronic obstructive pulmonary disease
      (COPD) in the elderly, a survey of attitudes to the COPD guideline prepared by
      the Japanese Respiratory Society, and a survey of the therapies actually used for
      this disease among physicians belonging to the Yokohama Medical Association. The
      results showed that most respondents thought that physicians, mainly except for
      respiratory physicians, miss the COPD patients because of failure to recognize
      COPD. The spread of the COPD guideline among physicians and the amount of therapy
      conducted according to this guideline were also insufficient. However, most
      physicians who know this guideline have used it well, and have also appreciated
      the contents. Thus, the results of our surveys suggested that this COPD
      guideline, with its step-by-step pharmacologic therapy, should be more widely
      disseminated, mainly among clinics and physicians that are not respiratory
      specialists. This would enable them to follow the guideline and improve their
      treatment of COPD. In addition, it was also supposed that the comprehensive
      respiratory rehabilitation should be more executed in the hospitals.

PMID- 11974866
TI  - [A case of loxoprofen-induced pneumonitis pathologically resembling
      hypersensitivity pneumonitis].
AB  - A 66-year-old woman was admitted to our hospital because of high fever, general
      fatigue, hypoxemia and liver dysfunction. Chest radiographs showed diffuse
      interstitial shadows in both lungs. We suspected drug-induced pneumonitis because
      of her history of drug administration for upper respiratory infection. Her
      symptoms and findings were markedly decreased by discontinuation of the drugs.
      Transbronchial lung biopsy specimens showed infiltration of eosinophils and
      lymphocytes to the alveolar septa, granuloma with Langhans' giant cells, and
      Masson bodies in a manner suggestive of hypersensitivity pneumonitis. Drug
      lymphocyte stimulation tests were negative except for loxoprofen. There was no
      recurrence of systemic or respiratory symptoms during overnight stays at home. On
      the basis of these findings, we arrived at a diagnosis of drug-induced
      pneumonitis caused by loxoprofen.

PMID- 11974867
TI  - [Recurrence of inflammatory pseudotumor of the lung with endobronchial lesion
      after resection].
AB  - A 74-year-old man was admitted to our hospital because of an abnormal shadow in
      the left middle lung field on chest radiography. Since a transbronchial biopsy
      was not diagnostic, a left lower lobectomy was performed. Histopathologically,
      the patient was diagnosed as having an inflammatory pseudotumor of the lung. Four
      months after the surgery, the patient was readmitted with hemosputum.
      Bronchoscopically, an endobronchial lesion was found in the left main bronchus.
      Transbronchial biopsy of the lesion showed proliferation of inflammatory cells
      compatible with inflammatory pseudotumor. Therefore, a recurrent inflammatory
      pseudotumor was diagnosed. Treatment with corticosteroid resulted in the
      disappearance of the endobronchial lesion and the erythrocyte sedimentation rate
      (ESR) returned to normal. The patient showed a prolonged elevation of ESR even
      after the resection, suggesting that the ESR may be a good indicator of the
      activity of this disease.

PMID- 11974868
TI  - [Spontaneous resolution of Pneumocystis carinii pneumonia].
AB  - A 58-year-old woman was admitted to our hospital complaining of fever, dry cough,
      and exertional dyspnea. Chest radiographs showed diffuse interstitial infiltrates
      in both lungs, and blood gas analysis showed moderate hypoxemia. The levels of
      serum KL-6 and beta-D-glucan were markedly elevated. Bronchoscopy was performed
      and Pneumocystis carinii was found in the BALF and transbronchial lung biopsy
      specimens. A positive reaction for the HTLV-I antibody was obtained, and HTLV-I
      proviral DNA was demonstrated. A conclusive diagnosis of Pneumocystis carinii
      pneumonia in a smoldering ATL patient was made on these grounds. Without specific
      treatment for Pneumocystis carinii pneumonia, the symptoms and abnormal chest
      radiographic findings disappeared. This case suggests that the fluctuation in
      cell-mediated immunity associated with HTLV-I carriers may allow recovery from
      Pneumocystis carinii pneumonia even without antipneumocystis therapy.

PMID- 11974869
TI  - [Adenocarcinoma of the lung with skeletal muscle metastasis, resulting in death
      due to myocardial metastasis: a case report].
AB  - A 57-year-old man was admitted to the hospital because of multiple subcutaneous
      masses with pain, mild dyspnea, and bloody sputum. He had been asymptomatic until
      one month earlier, when he began to have a dry cough and myalgia of the right
      forearm. A chest radiograph showed cardiomegaly. Whole-body computed tomographic
      scan, cytologic examination of the sputum, and histological examination of a
      subcutaneous nodule on the scalp resulted in the diagnosis of lung cancer with
      multiple organ metastases, including those to skeletal muscle and myocardium.
      Despite chemotherapy, he died suddenly on the 45th hospital day. Autopsy revealed
      that about half of the myocardium had been replaced by metastatic tumors, so we
      speculated that he died from heart failure due to cardiac muscle metastasis.

PMID- 11974870
TI  - [A case of true pulmonary carcinosarcoma].
AB  - A 72-year-old male was admitted to our hospital because of dyspnea. A chest
      radiograph showed a mass shadow measuring 40 x 40 mm in the left lower lobe, and
      fiberoptic bronchoscopy revealed obstruction of the left B8 by the tumor.
      Adenocarcinoma was suspected after a transbronchial biopsy, and left lower
      lobectomy was performed. Histologically, the resected specimen was composed of
      carcinomatous and sarcomatous elements, and further immunohistological study
      revealed that the former component was poorly differentiated squamous cell
      carcinoma and the latter was fibrosarcoma. We therefore concluded that the tumor
      was a true carcinosarcoma of the lung.

PMID- 11974871
TI  - [A case of recurrent aspiration pneumonia by achalasia].
AB  - A 56-year-old woman came to our hospital with the symptoms of anorexia, body
      weight loss and sustained cough. Chest radiography showed diffuse, rounded, high
      attenuation areas in both lung fields. The diagnosis was difficult, but, because
      of the symptoms and chest radiograph, we suspected miliary tuberculosis. Finally,
      we diagnosed her illness as achalasia with aspiration pneumonia, because we found
      a dilated esophagus and diffuse, rounded, high attenuation areas in chest CT scan
      films. Neither Mycobacterium tuberculosis nor tuberculous granulation was present
      in transbronchial lung biopsy specimens. Only inflammation was found in those
      slides. The gastrofiberscope was useful for searching for tumors, but not for
      diagnosing achalasia. Consequently, we identified the achalasia from the
      radiographic findings with the use of barium, but the patient's symptoms might
      not have led to that diagnosis because she was younger than the age range in
      which aspiration pneumonia usually occurs. The achalasia was treated with surgery
      rather than balloon dilation, since that was the patient's choice. Three months
      after surgery, her lungs had improved and body weight had increased by about 10
      kg.

PMID- 11974872
TI  - [A case of central diabetes insipidus caused by metastatic small cell lung
      cancer].
AB  - A 58-year-old man was admitted to our hospital because of cough, polydipsia and
      polyuria. Chest CT films showed mediastinal lymphadenopathy, nodules in the lung
      fields, and pleural effusion. Histopathologic examination of transbronchial
      biopsy specimens showed oat cell carcinoma. MRI films revealed tumorous swelling
      of the pituitary stalk. Central diabetes insipidus caused by pituitary metastasis
      of small cell lung cancer was diagnosed. After treatment with whole-brain
      irradiation and chemotherapy, the size of the swollen pituitary stalk was reduced
      and his urine volume decreased. He died of respiratory insufficiency 15 months
      after the initial diagnosis. No recurrence of pituitary metastasis was apparent.
      This was a rare case of central diabetes insipidus caused by pituitary metastasis
      of small cell lung cancer successfully treated with radiotherapy and
      chemotherapy.

PMID- 11974873
TI  - [Desquamative interstitial pneumonia--case report and review of literature].
AB  - A 50-year-old man was admitted to our hospital because diffuse reticulonodular
      shadows in the bilateral lung fields had deteriorated on chest radiographs during
      a regular checkup. The bronchoalveolar lavage (BAL) fluid revealed an increase in
      the total number of cells, including slightly elevated levels of eosinophils and
      neutrophils. The thoracoscopic lung biopsy specimens showed findings compatible
      with desquamative interstitial pneumonia (DIP). Corticosteroid therapy was done,
      and improvement of chest CT findings and pulmonary function were seen. We
      reviewed the clinical features in seventeen patients with biopsy-proven DIP
      reported in Japan. All patients have good prognoses and a high frequency of
      steroid responsiveness. Moreover, many patients were positive for antinuclear
      antibodies in serological tests, and there was a tendency toward increasing
      eosinophils in BAL fluids.

PMID- 11974874
TI  - [A case of sternal chondrosarcoma with multiple pulmonary embolisms].
AB  - A 63-year-old man was admitted to our hospital because of a large, firm tumor in
      the upper region of the anterior chest wall. The tumor measured 8 x 10 cm in
      diameter. A diagnosis of chondrosarcoma of the sternum was made cytologically
      from a percutaneous fine needle aspiration biopsy. The primary tumor was
      completely resected, but the sternum, ribs and clavicles were only partially
      resected. Another tumor was detected five months after resection and metastasis
      to the brain was recognized in December 2000. The patient, now suffering
      headaches and vomiting due to the intracranial hemorrhage around the metastatic
      lesion in the brain, was readmitted. Although temporary improvement of his
      general condition was achieved by conservative treatment, he suddenly died of
      respiratory failure because of multiple tumor emboli in the pulmonary artery.
      This was a very interesting case in that the chondrosarcoma was of sternal origin
      and was complicated by tumor emboli in the pulmonary artery.

PMID- 11974875
TI  - [Imaging of Wegener's granulomatosis: changes by serial chest CT].
AB  - We reviewed the chest radiographs and serial CT scans of two patients with
      pathologically confirmed Wegener's granulomatosis. The radiographs revealed
      multiple nodules or masses with and without cavitation, as well as
      consolidations. Lung lesions on CT included multiple pulmonary nodules and masses
      of varying size, cavities, consolidations with air bronchogram. Bronchovascular
      bundle thickening and lymph node swelling were also seen on CT. Some lung nodules
      or masses demonstrated feeding vessels or wedge-shaped lesions, or both, abutting
      the pleura. Follow-up CT before treatment showed that the multiple nodules had
      increased in size, resulting in masses and consolidations with air bronchogram.
      After treatment, almost all nodules disappeared without scarring, while the
      masses and consolidation resolved with residual scarring, and the cavity was
      transformed to a cystic lesion by follow-up CT. The bronchovascular bundle
      thickening and lymph node swelling showed improvement.

PMID- 11974876
TI  - [Clinical evaluation of rounded atelectasis induced by exposure to asbestos].
AB  - We encountered 15 patients with rounded atelectasis induced by exposure to
      asbestos from 1992 to 1999. All patients were men whose ages ranged from 42 to 85
      years, with a mean age of 64.2 +/- 11.5 years. Rounded atelectasis was present
      only in the right lung and two patients had 2 rounded atelectasis in the right
      lung. In eight cases, the rounded atelectasis was found in segment 10, while in
      the others, it was found in segments 4, 5, 6, 8, and 9. Although evidence of
      symptoms was absent, rounded atelectasis was detected in six patients through
      medical examinations. Others complained of chest pain and dyspnea. Thirteen
      patients displayed pleural plaques and only 2 patients revealed asbestosis.
      Malignant complications were discovered in 4 patients, of whom 3 showed primary
      lung cancer and 1 suffered acute myelocytic leukemia. In their occupational
      histories, 7 patients had been exposed to asbestos in the shipyards and 5 in the
      construction field. The mean period of the exposure was 25.1 +/- 12.7 years, and
      the latency period from the first asbestos exposure to the detection of
      atelectasis was 35.1 +/- 8.8 years. Five autopsied patients had more than 10,000
      asbestos bodies in the lung, which indicated heavy exposure to asbestos. These
      results suggest that rounded atelectasis may appear after high-dose exposure to
      asbestos.

PMID- 11974877
TI  - [Allergic rhinitis epidemiology in Japan].
AB  - We epidemiologically surveyed allergic rhinitis nationwide, mailing
      questionnaires to 9,471 otorhinolaryngologists and their families nationwide in
      June 1998 responses by the end of September 1998: 42.8%, providing 17,301
      subjects. Few differences were seen in the age composition between the subject
      population and the general Japanese population. Cedar pollinosis morbidity after
      adjustment for population distribution was 17.3%, higher overall on the Pacific
      Ocean side and in central districts of Japan compared to districts on the Sea of
      Japan and the Inland Sea and lower in high or low latitudes. By age, morbidity
      increased sharply among subjects in their teens and decreased among subjects in
      their 60s. Morbidity was high in districts of heavy cedar pollen dissemination.
      By housing, morbidity was high in the suburbs, followed by residential areas and
      cities. Pollinosis due to causes other than cedar pollen showed results similar
      to those for cedar pollinosis in morbidity by age and the relationship between
      the housing environment and morbidity, with morbidity after population
      distribution adjustment 11.7%. Morbidity of perennial allergic rhinitis after
      adjustment for population distribution was 19.8% was slightly higher than that of
      pollinosis. By age, morbidity increased sharply at 5 to 9 years of age, being
      highest in the young than in cedar pollinosis; no decrease in morbidity after age
      60 was seen. Unlike cedar pollinosis, perennial allergic rhinitis showed no
      difference in morbidity by area or housing environment. The present survey using
      otorhinolaryngologists and their families nationwide as subjects enabled us to
      find areawise differences in morbidity for cedar pollinosis and perennial
      allergic rhinitis. Ours is useful epidemiologically in allergic rhinitis mainly
      for cedar pollinosis in Japan because it is superior to other questionnaires in
      response and because reply reliability is high.

PMID- 11974878
TI  - [Neurotological long-term follow-up in Minamata disease in Niigata, Japan].
AB  - To determine the long-term influence of organic mercurial intoxication on
      audiological and equilibrium findings, we followed up 36 patients
      neurotologically during 1980-1987 and 1991-2000 at Kido Hospital in Niigata.
      Typical findings were as follows: 1. In pure-tone audiometry, 24 of 72 ears (33%)
      showed slight hearing deterioration and 3 (4%) showed improvement. 2. Spontaneous
      nystagmus had disappeared in 5 patients (14%), but appeared in new 13 patients
      (36%). Positional nystagmus did not improve in any patient, and deteriorated in
      11 (31%). 3. In optokinetic nystagmus (OKN) tests, especially in vertical OKN
      test showing significant deterioration (44%). 4. The caloric nystagmus test
      showed marked deterioration (47%). Body-equilibrium testing showed slight
      deterioration in 11 patients (31%) and improvement in 5 (14%). Neurotological
      findings thus varied widely among patients and we were concluded that these
      differences were caused both by duration of methyl mercury contamination and by
      aging factors in patients.

PMID- 11974879
TI  - [2001 survey of pollen in Wakayama City with a real-time pollen counter].
AB  - Self-care is gradually being recognized as important in the treatment of
      pollinosis, based up to now on data on airborne pollen. To determine the real
      time numbers of airborne pollen would be more useful in self-care, however, so we
      studied the usefulness of the real-time pollen counter. Between Feb. 2, 2001, and
      Apr. 26, 2001, 4 types of airborne pollen i.e., Japanese cedar, Japanese cypress,
      black alder, and beech observed in Wakayama City were counted with a Durham
      pollen counter and a real-time pollen counter (Yamato Manufacturing Co. Ltd.).
      Correlation between the 2 pollen counters was r = 0.69 for Japanese cedar in
      March and r = 0.89 for Japanese cypress in April. A high correlation was observed
      between outcomes of the 2 pollen counters. The amount of pollen from black alder
      and beech was less than that from Japanese cedar and cypress. Unexpected peaks
      were observed not related to the pollen number is apparently due to snow. We have
      taken measure against snow, so we concluded that the real-time pollen counter was
      useful in counting the amount of airborne pollen over time.

PMID- 11974880
TI  - [Three-dimensional analysis of human Ebner's gland].
AB  - We analyzed changes in Ebner's gland with aging by 3-dimensional analysis to
      determine the relationship between the gland and the sense of taste. Samples were
      collected from Circumvallate papillae of the tongue in autopsied cases. After
      dehydration, samples were embedded in paraffin and cut into slices 5 microns
      thick for every 100 microns. Hematoxylin-Eosin staining was done. The section was
      photographed in black and white and printed. Three tissues, circumvallate
      papillae, epithelium, and Ebner's gland were identified and traced on an OHP
      sheet and imput to a computer. The cubic volume of Ebner's gland was measured by
      Cosmozone 2SA 3-dimensional analysis software by and acinar cell occupancy I-BAS
      one imaging analysis. A total of 60 cases from age groups in them 30s, 40s, 50s,
      60s, 70s, and 80s were used. Each group contains 5 men and 5 women. The mean
      cubic volume of Ebner's gland in the 30s was 67.0 mm3, in the 40s was 64.6 mm3,
      in the 50s was 59.8 mm3, in the 60s was 39.2 mm3, in the 70s was 33.9 mm3, and in
      the 80s was 30.4 mm3. Statistical analysis showed a significant difference in
      Ebner's gland cubic volume between age groups at p < 0.01. In acinar cell
      occupancIEs the coefficient of correlation was -0.858 in men and -0.838 in women
      with the correlation diagram showing a negative correlation. The acinar cell
      occupancy decreases with age for the presumed acinar cell volume in the Ebner's
      gland, the coefficient of correlation was -0.929 in men and -0.854 in women, with
      the correlation diagram showing a negative correlation. The presumed acinar cell
      volume decreases with age. We concluded that Ebner's gland is concerned
      indirectly with diminished sensitivity of the sense of taste with aging.

PMID- 11974881
TI  - [Evaluation of safe surgical treatment of peritonsillar abscess using computed
      tomography].
AB  - With the development of new antimicrobial agents, the incidence of peritonsillar
      abscess (PTA) is on the decline. PTA is still often encountered in general
      practice, however, where it requires immediate diagnosis and treatment. Because
      the internal carotid artery runs medially to the medial parapharyngeal space,
      damage to nearby vascular or other structures is a surgical risk of PTA. We used
      contrast computed tomography (CT) from PTA patients to investigate the anatomical
      relationship between the abscess and parapharyngeal space, and to determine safe
      surgical sites. We observed 31 patients with PTA--19 men and 12 women--between
      February 1997 and April 1999, all examined by contrast CT and undergoing drainage
      or incision. The average age was 30.7 years (range: 12-54 years). The abscess was
      on the right side in 20 cases and on the left side in 11. We determined the sites
      of the abscess and carotid artery, internal jugular vein, and surrounding soft
      tissue density area including nerves in the parapharyngeal space based on the
      angle and distance from recognizable anatomical structures in CT scans. The
      anterior margin of the parapharyngeal space was 29 +/- 5 mm posterior from the
      upper posterior alveolar margin. The medial margin of that space was at 15 +/- 2
      degrees laterally from the midline of the incisors, and 24 +/- 4 mm laterally
      from the midline sagittal plane. The internal carotid artery was located medially
      to the parapharyngeal space, running on the sagittal plane containing the upper
      posterior alveolar margin. The distance from the anterior margin of the
      parapharyngeal space to the posterior wall of the PTA was 9 +/- 4 mm, and the
      distance to the anterior wall of the abscess (including the pharyngeal mucosa)
      was 31 +/- 5 cm. The relationship between the upper posterior alveolar margin and
      midline sagittal plane was useful for determining the site of the parapharyngeal
      space. Because the internal carotid artery is located on the same sagittal plane
      as the upper posterior alveolar margin, when conducting drainage or incision of
      PTA, we should advance sagittaLly from the point of incision to a depth of no
      more than 20 mm. If the tip of the instrument is kept medial to the sagittal
      plane of the upper posterior alveolar margin, effective treatment should be
      achievable without the risk of vascular damage.

PMID- 11974882
TI  - [Streptococcus dysgalactiae subsp. equisimilis possessing Lancefield's group A
      antigen].
AB  - We isolated Streptococcus dysgalactiae subsp. equisimilis with Lancefield's group
      A antigen from a patient in Osaka City. This clinical isolate formed beta
      hemolytic large colonies on sheep blood agar, and was catalase-negative gram
      positive cocci carrying Lancefield's group A antigen. Therefore, Streptococcus
      pyogenes and this clinical isolate could not be classified by the conventional
      method on the basis of Lancefield's group antigen. In addition, the rapid
      detection system of group A streptococci based on group A antigen detection
      techniques could not divide into two species. Recently, S. dysgalactiae subsp.
      equisimilis with Lancefield's group G antigen has been isolated from severe
      invasive streptococcal infection in an increasing frequency in Japan. A
      possibility that group A S. dysgalactiae subsp. equisimilis cause a serious
      infection from now on cannot be denied. Thus the discrimination of S. pyogenes
      from group A S. dysgalactiae subsp. equisimilis is very important. To identify
      beta-hemolytic streptococci, it is necessary to consider a serogrouping test as
      one of characteristics of streptococci, and to identify by checking biochemical
      tests like the PYR test.

PMID- 11974883
TI  - [An evaluation of syndromic surveillance for the G8 Summit in Miyazaki and
      Fukuoka, 2000].
AB  - Syndromic surveillance was performed during the G8 Summit held in Fukuoka and
      Miyazaki City in July 2000. Any case suspected as acute infectious disease was
      reported from designated medical facilities. Those cases were categorized in 5
      clusters including "hemorrhagic and skin symptoms", "respiratory symptoms",
      "gastroenteric symptoms", "neural symptoms", and "miscellaneous symptoms". To
      compare how closely these incidence trends were representing those of the
      infectious disease surveillance, these results were analyzed for two weeks. In
      Miyazaki, duplicated report were accepted when more than one symptom were found.
      The ratio of weekly reported number for each cluster was calculated for two
      weeks, and then the ratio for former/latter week was calculated for each cluster.
      The results from Fukuoka and Miyazaki surveillance revealed the average
      former/latter ratio +/- SD = 0.99 +/- 0.292, 95% CI; 0.71-1.28 and 1.19 +/-
      0.298, 0.93-1.45, respectively. These results indicate that syndromic
      surveillance is well represented with the infectious disease surveillance trends.
      Single reporting, employed in Fukuoka, was easier for analysis. Reported number
      for acute respiratory syndrome was larger than that of infectious disease
      surveillance, indicating that the latter could not detect non-reportable adult
      cases. Syndromic surveillance enables us to show the trend quickly and it can be
      carried out with smaller costs and human resources. This study concluded that a
      syndromic surveillance is effective for such high-profile events, but sometimes
      it is hard to analyze the trend accurately, because of insufficient period of
      baseline data, number and size of the reporting sentinel facilities.

PMID- 11974884
TI  - [The serotype and Shiga toxin type of Shiga toxin-producing Escherichia coli from
      humans and various animals].
AB  - To clear the route of STEC (Shiga toxin-producing Escherichia coli) infection to
      humans, we examined the serotype. Shiga toxin genotype and eae gene of STEC
      strains from humans and various animals. The most predominant serotype originated
      from humans was O157:H7, followed by O26:H11, and other serotypes were O91:H21,
      O103:H2, O111:NM, O121:H19, etc. The eae gene was found in 79 of 93 strains from
      human origin. The serotypes of STEC from cattle were significant by similar to
      that of STEC from humans. The eae gene was found in 44 of 87 strains from cattle.
      Shiga toxin genotypes possessed O157 strains from humans and cattle, were divided
      into six groups, stx1, stx2, stx2c, stx1 + stx2, stx1 + stx2c and stx2 + stx2c.
      Moreover, frequency rates of Shiga toxin genotypes of O157 were also similar to
      both human and cattle origins. The serotypes of STEC from sheep were also a
      little similar to that of STEC from humans. Seven of 8 strains from deer
      possessed stx2d gene that the strains from humans seldom possessed, and none of
      the strains possessed eae gene. In STEC originated from swine, 15 of 25 strains
      were O139:H1 that Shiga toxin genotype was stx2e. It was thought that the sources
      of STEC infection to human are cattle and sheep, and deer and swine had little
      possibility to human STEC infection.

PMID- 11974885
TI  - [A three-year review of acute respiratory tract infections caused by
      Streptococcus milleri group].
AB  - The objective of our study is to understand the clinical features of patients
      with acute respiratory tract infection associated with Streptococcus milleri
      group (SMG). Fifteen patients with SMG respiratory tract infection visited our
      hospital from July, 1997 through May, 2000. There were seven cases of pneumonia,
      two pulmonary abscess, three thoracic empyema and three acute bronchitis. The
      mean age of the patients was 57.8 years (range 16-87), twelve were males, and
      seven were smokers. The moderately to severe underlying diseases existed in
      thirteen patients (86.7%) and included the following: respiratory diseases
      (20.0%), history of the esophageal or gastric surgery (26.7%), central nerve
      system diseases (13.3%), alcohol intake (60.0%), hepatitis and pancreatitis
      (33.3%), diabetes mellitus (13.3%) and malignancy (6.7%). The species of SMG
      detected were as follows: S. constellatus, 8, S. anginosus, 6 and S. intermedius,
      1. Anaerobic organism and other microorganisms were detected in five patients. A
      patient with SMG nosocominal pneumonia who previously had thoracic surgery for
      esophageal cancer died. Antibiotics therapy with carbapenem or combination
      therapy, drainage and no surgery, were successful in 14 of the 15 cases (93.3%).
      The number of intermediately or complete resistant strains against penicillin G,
      ampicillin and cefmetazole were 5 (33.3%), 8 (53.3%) and 12 (80.0%), respectively
      in this series. Recently, it is seemed that acute respiratory tract infections
      caused by SMG are increasing in the patients with moderately to severe underlying
      diseases, and several clinical strains of SMG are acquiring a tolerance to
      antibiotics.

PMID- 11974886
TI  - [Alterations in epidemics and vaccination for measles during a 20 year period and
      a strategy for elimination in Kurashiki City, Japan].
AB  - In Japan, an epidemic of measles occurs every few years. An estimated 100-200,000
      people contract the disease each year and 50-100 patients die. Following the
      eradication of poliomyelitis, the World Health Organization made plans for global
      eradication of measles, and the Japanese Association of Pediatricians began
      advocating vaccination to eliminate measles in Japan by 2005. However, no big
      response has occurred nationwide. Therefore, we retrospectively look at changes
      in epidemics and measles vaccination during the past 20 years in Kurashiki City,
      Okayama Prefecture and developed a strategy for elimination through the results.
      The Japanese surveillance showed the numbers of measles patient in Okayama to be
      a few times higher than the mean number nationwide. The number of persons
      vaccinated was approximately 2,000-3,000 per year, while the number of births was
      about 6,000 per year. After passing a revised vaccination law in 1994, the number
      of vaccinations increased to more than 4,000, and the epidemic situation
      decreased to the nationwide level. However, the number of measles patients older
      than 15 years of age who were admitted to our hospital increased from 4% to 24%
      in the ratio to the whole. In the United States, school regulations require that
      children be vaccinated for MMR twice before admission to school, but the revised
      vaccination law in Japan was changed from a requirement to a recommendation. To
      eliminate measles, we should increase the vaccination rate for infants, and
      should vaccinate adolescents who have not been vaccinated or do not have a past
      history of measles. It is important to choose the subjects and then confirm their
      vaccination after the recommendation. We have developed a strategy that includes
      1) advocacy for vaccination 2) selection for vaccination, 3) request for
      certification of vaccination, 4) convenience for vaccination. The goal after two
      years is for 1) a vaccination rate of more than 90% by end of one year of age, 2)
      a rate of vaccination and past history of measles in more than 90% of children
      before admission to kindergarten or public school.

PMID- 11974887
TI  - [Diagnosis of bacterial pneumonia by serum beta-globulin demarcation].
AB  - We studied whether the consolidation whose serum beta-globulin demarcation showed
      more than 12% was bacterial pneumonia or not. The materials were the patients
      with fever (> or = 37 degrees C) and the consolidation on chest-X ray film, the
      value of serum beta-globulin demarcation was more than 12% from 1995 to 2000.
      There were 5 cases with drug-induced pneumonitis, 5 cases with BOOP, 2 cases with
      eosinophilic pneumonia, 1 case with lung cancer (adenocarcinoma), and 1 case with
      interstitial pneumonia with dermatomyositis. No one had bacterial pneumonia.
      These results suggested the consolidation with fever whose serum beta-globulin
      demarcation showed more than 12% was not bacterial pneumonia.

PMID- 11974888
TI  - [Pneumonia associated with lung cancer in the elderly].
AB  - We investigated the clinical characteristics separating pneumonia as a
      complication in elderly lung cancer patients into obstructive and non-obstructive
      pneumonia. Two hundred and five patients with pneumonia as a complication in
      elderly lung cancer patients were classified into two groups; 64 patients with
      obstructive pneumonia and 141 patients with non-obstructive pneumonia. Most of
      the patients in both groups were male. Concerning histological findings, while
      most of the patients with obstructive pneumonia had squamous cell carcinoma,
      those with non-obstructive pneumonia had the same proportion of squamous cell
      carcinoma as all elderly patients with lung cancer. Most of the patients with
      obstructive pneumonia were in good general condition including their nutritional
      condition, but the patients with non-obstructive pneumonia were in significantly
      poor condition. A low percent of microorganisms were isolated from the sputum
      obtained from the patients with non-obstructive pneumonia, but a high percentage
      were obtained from those with non-obstructive pneumonia. Frequent involvement of
      gram-negative bacilli such as Pseudomonas aeruginosa and Klebsiella pneumoniae or
      Staphylococcus aureus containing MRSA was also found in these patients. Regarding
      treatment, although carbapenem was used either alone or in combination therapy as
      the regimen of treatment for pneumonia as a complication in elderly lung cancer
      patients with both the obstructive and non-obstructive pneumonia patients, the
      efficacy rate was poor in 50% with obstructive pneumonia and in 26% with non
      obstructive pneumonia. The mortality rate was 11% in the patients with
      obstructive pneumonia, while it was 61% in the patients with non-obstructive
      pneumonia. The prognosis was significantly poorer in the patients with non
      obstructive pneumonia. We concluded that although the prognosis was not so poor
      for patients with obstructive pneumonia if the appropriate treatment was given,
      in the patients with non-obstructive pneumonia, the treatment for underlying
      diseases and the improvement of their general condition, including the
      determination of causative microorganisms, was important.

PMID- 11974889
TI  - [Neutralizing activity of human immunoglobulin preparation against toxic shock
      syndrome toxin-1].
AB  - Human intravenous immunoglobulin (IVIG) preparation containing a variety of
      antibodies is widely used against severe infectious diseases. Although IVIG is
      supposed to promote phagocytosis of opsonized bacteria and neutralize several
      bacterial toxins, it is unclear what antibodies are responsible for the effect in
      clinical use. In this study, we found that IVIG showed neutralizing activity
      against toxic shock syndrome toxin-1 (TSST-1), produced by methicillin-resistant
      Staphylococcus aureus (MRSA). Whereas intravenous inoculation with culture medium
      of MRSA 1945 strain into ICR mice causes immediate death, all of the mice
      survived in case of previous administration of IVIG. Such effect might be
      attributed to neutralization of TSST-1. Murine splenocytes incubated with TSST-1
      (1.0 ng/mL) for 48 hours produced IFN-gamma. By addition of IVIG at 100
      micrograms/mL into culture medium, production of IFN-gamma was completely
      inhibited. From IVIG, anti-TSST-1 antibody was purified by affinity
      chromatography as one of the effective antibodies. MRSA 1945 mixed with dextran
      based microcarrier beads and injected subcutaneously into mice resulted in the
      formation of abscess and excretion of TSST-1 in serum for 14 days. IVIG and anti
      TSST-1 antibody neutralized TSST-1 in blood 24 hours after infection, although
      bacterial count was kept constant. Experimental rabbit TSS model was established
      by synergism with lipopolysaccharide (LPS) of Escherichia coli. Anti-TSST-1
      antibody protected NZW rabbits from lethal challenge with TSST-1 (1 microgram/kg,
      i.v.) 4 hours before LPS in a dose-dependent manner (10 micrograms/kg, i.v.),
      whereas all of the NZW rabbits died in the control group. Thus, IVIG may be a
      useful tool in the prevention and perhaps therapy of staphylococcal infections
      and TSS.

PMID- 11974890
TI  - [Comparison between HIV-1-infected hemophiliacs and non-hemophiliacs on survival
      and clinical courses after starting highly active antiretroviral therapy].
AB  - In order to investigate the long-term prognosis and clinical efficacy of highly
      active antiretroviral therapy (HAART) in HIV-1-infected hemophiliacs, we compared
      clinical courses of 69 HIV-1-infected hemophiliacs and 29 non-hemophiliacs all of
      whom were asymptomatic between 1990 and 1993. Changes of CD4 count during 1990
      through 2000 in both groups were not significantly different. The time to death
      due to AIDS in both groups were also not significantly different. The major
      causes of death not related to AIDS in hemophiliacs were bleeding, liver
      cirrhosis, and liver cancer. A total of 55 (39 hemophiliacs and 16 non
      hemophiliacs) out of 98 patients survived in 1997. Since then, the 28
      hemophiliacs and the 12 non-hemophiliacs received HAART. Although the percentage
      of patients whose viral loads (VL) decreased to below undetectable level (VL <
      400 copies/ml) by the initial HAART regimens without saquinavir were not
      significantly different, continuation of the same regimens in the hemophiliacs
      were significantly longer than non-hemophiliacs (84 weeks vs. 51 weeks, p <
      0.05). From starting HAART to July 2000, 35.7% of the hemophiliacs were changed
      regimens three times or more. That is higher prevalence comparing with non
      hemophiliacs of 16.7%. This study suggests that there might be the patient group
      who have to been changed HAART regimens frequently in the hemophiliacs.

PMID- 11974891
TI  - [A case report of pulmonary nocardiosis associated with bronchiectasis after
      pulmonary tuberculosis successfully treated with sparfloxacin].
AB  - A 48-year-old female with bronchiectasis after pulmonary tuberculosis was
      admitted to our hospital because of bloody sputum and multiple cavity formation
      in the right lung. Chest X-ray & CT films revealed diffuse nodular shadows and
      cavity formation with a thick wall. Nocardia asteroides was isolated from the
      stum but no other pathogenic bacteria was isolated. Administration of sulfame
      thoxazole-trimethoprim is not effective. The results of an MIC test for
      antimicrobial agents led to treatment with sparfloxacin and the clinical symptoms
      and cavity formations in the right lung improved. Nocardia asteroides may cause
      exacerbation of bronchiectasis.

PMID- 11974892
TI  - [Four cases of pediatric Ramsay Hunt syndrome].
AB  - Four cases of the Ramsay Hunt syndrome were admitted to our hospital during the
      two years from February 1997 to January 1999. Though one of the 4 patients had
      been immunized with varicella vaccine, the causative virus was not a vaccine
      strain but a wild-type strain. These patients were not suffering from underlying
      diseases. Because the number of pediatric zoster patient without underlying
      diseases who visited our clinic between 1981 and 1999 was 35 cases, the Ramsay
      Hunt syndrome turned out not to be extremely rare even among children having no
      underlying diseases. The prognosis of the Ramsay Hunt syndrome is assumed to be
      good if the treatment begins at the early stage. To begin the treatment at the
      early stage, it is necessary to confirm the diagnosis with virological
      examinations.

PMID- 11974893
TI  - [Pulmonary emphysema in klotho mutant mice (deficient in klotho gene expression):
      klotho gene essential in postnatal pulmonary integrity].
AB  - The homozygous mutant klotho (KL-/-) mouse, which is deficient in klotho gene
      expression, exhibits multiple phenotypes resembling human aging that include a
      short life span, arteriosclerosis, osteoporosis, skin atrophy, and ectopic
      calcifications. Histologic examination of KL-/- mice at 4 weeks of age reveals
      pulmonary emphysema. The emphysematous changes are not caused by a developmental
      defect or hypoplasia of the lung. The lungs of heterozygous mutant klotho (KL+/-)
      mice show emphysematous changes and alveolar calcification which are almost
      identical to those in KL-/- mice. These observations indicate that the klotho
      gene expression is essential to maintaining normal alveolar architecture in
      postnatal life. Pulmonary function tests reveal prolonged expiration time in KL-/
      mice. The expression of type IV collagen and surfactant protein-A mRNA is
      markedly upregulated in KL-/- mice, suggesting that a defect in matrix synthesis
      or in type II pneumocyte function, or both, may be involved in the pathogenesis
      of pulmonary emphysema in this mutant. Several animal strains have been reported
      to develop pulmonary emphysema, but the klotho mouse is unique because it
      simultaneously exhibits various aging phenotypes. Analysis of pulmonary emphysema
      in klotho mice will provide a unique insight into the relationship between
      pulmonary emphysema and aging.

PMID- 11974894
TI  - [Pulmonary involvement in sarcoidosis: CT findings at diagnosis and their changes
      at follow-up in cases without corticosteroid treatment].
AB  - To review the pulmonary CT findings in sarcoidosis at diagnosis, and to analyze
      the change in each finding at follow-up in cases without corticosteroid
      treatment. The study included 21 cases of pulmonary involvement of sarcoidosis.
      We analyzed the presence or absence and grade of each HRCT finding: bronchial
      wall thickening, enlargement of vascular shadows, pleural involvement, septal
      thickening, small nodules, ground-glass opacities, centrilobular opacities,
      consolidation, nodules, and volume loss. Afterwards, we compared the initial CT
      with the follow-up CT, and described the change of each finding as "improved" or
      "not improved". Furthermore, we decided if each case as a whole was improved or
      not after considering all of the pulmonary CT findings. Twelve of the 21 cases
      were improved. Small nodules, ground-glass opacities, centrilobular opacities,
      and nodules had improved in more than 50% of the cases since the initial CT.
      However, pleural involvement (10/11) and volume loss (6/9) were not improved.
      Pleural involvement and volume loss correlated the radiological irreversibility
      (p < 0.05). Of the several pulmonary CT findings in sarcoidosis, pleural
      involvement and volume loss show the highest rates of irreversible pulmonary
      changes.

PMID- 11974895
TI  - [Clinical effect of high inhalation flow from a fluticasone diskhaler in chronic
      asthma].
AB  - The optimal inhalation flow of dry powder formula fluticasone dipropionate (DFP)
      is not known. This study investigated the clinical effects of inhaling a flow of
      DFP. A randomized cross-over trial was applied to 13 patients with chronic
      persistent asthma. After a 2-week run-in period using the current dose of
      beclomethasone from a metered dose inhaler (BDP-run), BDP was replaced with an
      equipotent amount of DFP. The patients entered either an 8-week run with high
      flow (> 100 L/min) inhalation followed by a 4-week run with medium-flow (70
      L/min) (HM group) or a medium-flow run followed by a high-flow run (MH group).
      The peak inhaling flow from DFP was measured daily. The mean of the inhalation
      flow in the high-flow run (111.4 +/- 3.6 (SE) L/min) was significantly higher
      than that (77.3 +/- 0.6 L/min) in the medium-flow run. In both groups, morning
      and evening peak expiratory flows (PEFs) increased in the first week of change
      from BDP to DFP, peaking in the first 8-week run, then maintained this level
      until the end of the following 4-week run. When PEFs in the last week of the 3
      runs were compared, those during the DFP-run of either flow were significantly
      larger than those during the BDP-run, but the PEFs during the high-flow and
      medium-flow runs were not significantly different. The asthma symptoms also
      improved with a change from BDP to DFP, but the symptoms did not change with a
      change in the inhalation flow rate. An inhaled flow of up to 111 L/min is
      acceptable in terms of clinical efficacy for the use of DFP.

PMID- 11974896
TI  - [A case of eosinophilic pneumonia induced by Pelex granule].
AB  - We report a case of eosinophilic pneumonia induced by Pelex granule. A 31-year
      old male patient had been treated with Pelex granule and other drugs for common
      cold symptoms such as cough and fever. Since these symptoms were persistent, he
      was admitted to our hospital for further examination. His laboratory findings
      showed eosinophilia and a mild elevation of serum IgE. Chest radiography revealed
      a reticular shadow and patchy shadows in both lung fields. Analysis of the
      bronchoalveolar lavage fluid (BALF) showed an increased percentage of
      eosinophils. The histological findings of the specimen obtained by transbronchial
      lung biopsy showed infiltration of eosniophils into the alveolar walls and
      spaces. After withdrawal of all drugs, the patient's clinical findings-symptoms,
      laboratory data, and chest radiographic findings-soon improved. A lymphocyte
      stimulation test (LST) for Pelex granule was positive. Taken together, the case
      was diagnosed as eosinophilic pneumonia induced by Pelex granule.

PMID- 11974897
TI  - [A case of Paragonimus miyazakii with migrating infiltrates: use of ELISA in
      diagnosis and treatment].
AB  - A 47-year-old man was referred to our clinic with abnormal chest radiographs. He
      was free of symptoms, but his chest CT demonstrated transient migrating
      infiltrates. Peripheral blood revealed eosinophilia and eosinophilic pneumonia
      was suspected. However, the bronchoalveolar lavage fluid showed no increase in
      eosinophils. Later, the patient's pleural effusion did contain eosinophils. His
      total IgE level was continuously elevated despite the absence of allergic
      disease, and so parasitic infection was suspected. Ouchterlony's double diffusion
      test after absorption of Paragonimus westermanii antigen was positive for
      Paragonimus miyazakii antigen. The ELISA values of both serum sample and pleural
      effusion were increased. As the ELISA value of the pleural effusion was higher
      than the serum one, we realised that pleural effusion was caused by Paragonimus
      miyazakii. Treatment with praziquantel for 3 days resulted in disappearance of
      the abnormal chest radiographic findings, and a reduced blood eosinophil level,
      IgE level and ELISA titre for Paragonimus miyazakii. We concluded that ELISA was
      useful in the diagnosis and assessment for treatment in Paragonimus miyazakii
      infections although there was no clearly relevant history.

PMID- 11974898
TI  - [A case of pulmonary infection induced by both Aspergillus sp. and Mycobacterium
      tuberculosis during corticosteroid therapy].
AB  - An 83-year-old woman with idiopathic thrombocytopenic purpura had received
      corticosteroid drugs since December 1998. Pulmonary aspergillosis appeared three
      months later, but improved with administration of itraconazole. When the dose of
      corticosteroid had to be increased again because of aggravation of the underlying
      disease after a 20-month gradually decreased use of the drugs, a new infiltration
      shadow in the left upper and middle fields appeared after one month of increase.
      Therefore, a detailed examination was performed. Mycobacterium tuberculosis was
      identified by the DDH method, Aspergillus sp. was isolated from the sputum
      culture, and aspergillus antigen was positive serologically, leading to a
      diagnosis of pulmonary infection induced by both Aspergillus sp. and
      Mycobacterium tuberculosis. Because of the prolonged administration of
      corticosteroid drugs, the patient was highly susceptible to infectious diseases.
      We considered this a case of interest because 20 months after the diagnosis of
      pulmonary aspergillosis, a mixed pulmonary infection of Mycobacterium
      tuberculosis and Aspergillus sp. was identified.

PMID- 11974899
TI  - [Follicular bronchiolitis preceding rheumatoid arthritis].
AB  - A 52-year-old woman visited our hospital because of a cough and stridor in 1994.
      She had a history of non-tuberculous mycobacteriosis and chronic paranasal
      sinusitis. Her chest CT scan showed scattered centrilobular nodular shadows and
      peribronchial thickening, and so we suspected recurrent non-tuberculous
      mycobacteriosis or diffuse panbronchiolitis. Clarithromycin treatment was
      initiated, but she soon ceased taking the drug. She visited our hospital again
      because of a severe cough three and half years later. A new chest CT scan showed
      increased abnormal shadows, and so we suspected worsening non-tuberculous
      mycobacteriosis or diffuse panbronchiolitis. Consequently, we commenced treatment
      with rifampicin, ethambutol hydrochloride as well as clarithromycin. One year
      later, rheumatoid arthritis was diagnosed because of a swollen proximal
      interphalangeal joint in both fourth fingers. Her respiratory symptoms were not
      relieved with clarithromycin or antituberculous drugs, so a thoracoscopic biopsy
      was performed for a more accurate diagnosis. Histological examination revealed
      follicular bronchiolitis.

PMID- 11974900
TI  - [Recurrence of thymoma accompanied with hypogammaglobulinemia 20 years after
      surgery: a case report].
AB  - We reported a case of recurrence of localized thymoma accompanied with
      hypogammaglobulinemia (Good's syndrome) 20 years after surgery. A 74-year-old man
      was admitted to this hospital because of mediastinal tumor and chronic pulmonary
      infection. He had been thymectomised at the age of 55 because of spindle cell
      thymoma. After that, he had been asymptomatic until January 1997, when he began
      to have a recurrent productive cough, and low-grade fever. Laboratory findings
      revealed hypogammaglobulinemia. Percutaneous needle biopsy of the mediastinal
      tumor revealed spindle cell thymoma. Therefore, hypogammaglobulinemia with
      thymoma (Good's syndrome) accompanied with a chronic lower respiratory tract
      infection was diagnosed. Immunologic studies revealed a marked decrease of CD 20
      positive cells and decreased lymphocyte activation under the stimuli of
      phytohemagglutinin and concanavalin A. The thymoma was resected in Dec 1997, but
      the serum immunoglobulin showed no increase at al.

PMID- 11974901
TI  - [An infection with Legionella pneumophila treated with intravenous
      ciprofloxacin].
AB  - A 60-year-old diabetic man who had had a coronary artery bypass graft operation
      was admitted to Okaya Enrei Hospital because of coughing, high fever and dyspnea.
      Chest high-resolution computed tomography scans revealed bilateral pleural
      effusions and left-sided alveolar shadows and ground glass opacity. These
      infiltrations in the left lung field showed rapid growth. Legionella pneumonia
      was diagnosed because of a high titer for Legionella pneumophila antigen in the
      urine. He was treated with 600 mg per day of parenteral ciprofloxacin for two
      weeks and 10 mg per day of oral prednisolone for the second week, resulting in
      improvement of the clinical findings.

PMID- 11974903
TI  - [A case of endobronchial sarcoidosis presenting as a polypoid lesion].
AB  - A 51-year-old woman was admitted to our hospital because of deterioration of
      abnormal chest shadows. Though the shadows had been pointed out at another
      hospital about two years before, no evaluation had been made at that time. A
      chest CT scan showed multiple small nodular shadows and thickening of the
      bronchovascular bundles bilaterally, and marked swollen lymph nodes in the
      axilla, mediastinum, and bilateral the hili of both lungs. Bronchoscopic
      evaluation revealed bronchial mucosal hypervascularity and a polypoid lesion at
      the orifice of the right B8b. The transbronchial biopsy specimen of the polypoid
      lesion showed non-caseating epithelioid cell granulomas in the bronchial mucosa.
      The bronchoalveolar lavage revealed a increase in the total number of cells
      including high levels of lymphocytes. Therefore, a diagnosis of sarcoidosis was
      made. This is a very rare case of endobronchial sarcoidosis. However, biopsy
      specimens of normal mucosa in sarcoidosis often show a microscopic sarcoid
      process, so a diagnosis of endobronchial sarcoidosis in this case should be given
      prudently.

PMID- 11974902
TI  - [Two fatal cases of methotrexate-induced interstitial pneumonitis].
AB  - We report two cases of methotrexate-induced pneumonitis. Both patients died
      despite steroid pulse therapy. Postmortem lung tissue revealed diffuse alveolar
      damage, and focal lung fibrosis. Physicians should be aware of the possibility of
      MTX-induced interstitial pneumonitis in diagnosing RA patients with MTX when
      diffuse pulmonary infiltration is present.

PMID- 11974905
TI  - [A case of primary cardiac lymphoma complicated by idiopathic thrombocytopenic
      purpura].
AB  - An 80-year-old woman was admitted to our hospital for investigation of left
      pleural effusion. A computed tomography (CT) scan of the chest revealed a tumor
      mass in the right anterior ventricular wall. Whole-body CT scans showed no
      extracardiac lesions. Scintigraphy with 67Ga citrate showed tracer accumulation
      in the heart and no accumulation in other regions. The cytology of the pleural
      effusion was consistent with non-Hodgkin's lymphoma. Primary cardiac lymphoma
      (PCL) was diagnosed. The tumor mass showed a marked reduction in size after 3
      cycles of chemotherapy, but thrombocytopenia unrelated to bone marrow failure
      appeared. Idiopathic thrombocytopenic purpura (ITP) was suspected and
      prednisolone therapy was begun, and ultimately brought about a partial remission.
      To date, no cases of ITP associated with PCL have ever been reported. Autoimmune
      disorders are occasionally associated with malignant lymphoma. No other case of
      the development of ITP as a complication of PCL could be found in the literature.

PMID- 11974904
TI  - [A case report of intralobar pulmonary sequestration with an anomalous artery
      originating from the celiac artery].
AB  - A 43-year-old female was admitted to our hospital because of an abnormality
      detected in chest radiography. Chest radiographs showed a nodular shadow behind
      the heart. Chest CT revealed a nodule connected to the descending aorta with
      increased blood flow in left lower lobe, suggesting the presence of a pulmonary
      sequestration. Bronchography showed an intralobar sequestrated lung in the left
      lower lobe. Aortography demonstrated that the sequestrated lung was fed by an
      anomalous artery 20 mm in diameter, originating from the celiac artery. From
      those findings, Pryce type IIintralobar pulmonary sequestration was diagnosed,
      and the left lower lobe was removed. Histological findings from the excised
      tissues showed mild dilatation of the bronchioles and hypervascularity.

PMID- 11974906
TI  - [Pulmonary empyema 48 years after Lucite-ball Plomb implantation for
      tuberculosis].
AB  - A 68-year-old woman was diagnosed as having empyema on the left side. She had a
      history of pulmonary tuberculosis and tuberculous pleurisy in 1949. She was
      treated with artificial pneumothorax and implantation of 7 Lucite-ball plombs in
      the left upper thorax. A chest radiograph taken 14 years after initial operation,
      revealed an increase in density inside some of the Lucite-ball plombs. She was
      again admitted after experiencing fever and dyspnea 48 years after initial
      operation. The chest radiograph then showed a large mass on the left side, which
      compressed the mediastinum to the right. Inside the mass, Lucite-ball plombs were
      detected. The fever and inflammatory findings were improved with antibiotic
      therapy, but the dyspnea was persistent. The Lucite-ball Plombs and coagulating
      tissue were removed successfully. The patient's symptoms and respiratory function
      improved after the second operation.

PMID- 11974907
TI  - [Recent advance in DNA polymerase research: discovery of the new molecular
      species].

PMID- 11974908
TI  - [Pol alpha-primase complex].

PMID- 11974910
TI  - [DNA polymerase epsilon].

PMID- 11974909
TI  - [DNA polymerase delta].

PMID- 11974911
TI  - [DNA polymerase beta].

PMID- 11974912
TI  - [Mechanism of translesion DNA synthesis by DNA polymerase zeta].

PMID- 11974913
TI  - [DNA polymerase eta: from a DNA repair-deficient genetic disease to the discovery
      of a novel DNA polymerase].

PMID- 11974914
TI  - [Biochemical studies of human DNA polymerase kappa and its transcriptional
      regulation].

PMID- 11974915
TI  - [A novel mammalian DNA polymerase: DNA polymerase lambda (pol lambda)].

PMID- 11974916
TI  - [Expression and function of terminal deoxynucleotidyl-transferase and discovery
      of novel DNA polymerase mu].

PMID- 11974917
TI  - [Mechanism for telomerase gene expression].

PMID- 11974919
TI  - [Inhibitors of eukaryotic DNA polymerases].

PMID- 11974918
TI  - [DNA replication fidelity in DNA replication system in vitro].

PMID- 11974920
TI  - [A study of school children with type A behavior pattern association of
      "competitiveness" and "impatience-aggression" with lifestyle-related factors].
AB  - PURPOSE: To study associations of the type A behavior pattern with the results of
      physical and blood examinations and data from a questionnaire on lifestyle for
      elementary school and junior high school students. METHODS: 277 elementary school
      students of 4th grade (9-10 y) and 297 junior high school students of 1st grade
      (12-13 y) in a community in Saitama who completed a test for the type A behavior
      pattern developed by Yamasaki, underwent physical and blood examinations for
      parameters like serum cholesterol, blood pressure, height and weight and were
      administered a questionnaire concerning lifestyle. RESULTS: Points of the test
      for a type A behavior pattern were higher in 9-10 y than in 12-13 y individuals
      (both sexes or boys). Factor analysis applying 17 items of the test for type A
      behavior as variables demonstrated two common factors; "competitiveness" and
      "impatience-aggression". Mean impatience-aggression scores for individuals were
      significantly higher in 9-10 y than in 12-13 y children; however, the
      competitiveness score showed no significant difference between the two groups.
      Higher competitiveness scores were shown by children who prefer sports or play
      sports after school, also in 9-10 y children not warned against excess eating or
      not eating slowly by their parents. Higher impatience-aggression scores were
      shown by children not preferring sports, not playing sports after school, eating
      while watching TV or reading books, and also in 9-10 y children eating until
      full, and in 12-13 y children not chewing foods well or who were warned of excess
      eating by parents. 12-13 y students having a higher atherosclerosis index showed
      low competitiveness and high impatience-aggression scores. CONCLUSION: By
      analyzing two factors included in the type A behavior pattern in school children,
      we found associations with lifestyle and the atherosclerosis index. The results
      provide a basis for further follow-up studies on the relationship between type A
      behavior pattern and prevention of future cardiovascular disease.

PMID- 11974921
TI  - [The relationship between ambulatory blood pressure variation and symptoms of
      depression and sleep disturbance in community-dwelling elderly persons with
      independent activities of daily living].
AB  - OBJECTIVE: To clarify the relationship between ambulatory blood pressure
      variation and symptoms of depression and sleep disturbance in community-dwelling
      elderly persons with independent activities of daily living. METHODS: The
      subjects were 41 volunteers in a health education class for the elderly in a
      rural community. We carried out: (1) an interview about symptoms of depression
      using the Geriatric Depression Scale (GDS), competence of daily living,
      subjective daily sleep complaints and past history of disease,; (2) ambulatory
      blood pressure measurements over 24 hours with a portable device,; (3) sleep
      awake judgment by wrist actigrams,; and (4) instructions for self-records of
      his/her life activities. RESULTS: (1) The average value for 24 hour-mean
      diastolic blood pressure was significantly higher in subjects undergoing
      hypertension treatment. (2) No significant relationship was observed between
      subjective sleep disturbance and ambulatory blood pressure variation. (3) No
      significant relationship was observed between objective sleep disturbance
      assessed by wrist-actigraphy and ambulatory blood pressure variation. (4) Severe
      depression was related to a lower degree of night decrease in both systolic and
      diastolic blood pressure in subjects undergoing hypertension treatment, while it
      was associated with higher average values for 24 hour- and awaking-mean systolic
      and diastolic blood pressure in subjects not receiving such treatment.
      CONCLUSIONS: In community-dwelling elderly persons with independent activities of
      daily living, severer depression was associated with the higher mean blood
      pressure in subjects not taking medicine for hypertension and with a low degree
      of night decrease in diastolic blood pressure in those receiving hypertension
      treatment, while no significant relationship was observed between sleep
      disturbance and ambulatory blood pressure variation.

PMID- 11974922
TI  - [Activity guideline for public health center nurses and important matters for
      system construction for large regions].

PMID- 11974923
TI  - [Standardized ratio of the elderly needing support or care among 23-ku(words) in
      Tokyo development of index for assessing effectiveness of public health
      activities targeting on prevention of disability among the elderly].

PMID- 11974924
TI  - [Variation in indoor air pollutant concentrations with time in a newly
      constructed private house].
AB  - An indoor air quality research project was conducted in a new private house built
      in January 1997 to investigate time course changes in formaldehyde concentrations
      during an 11-month period from April 1997 to February 1998. Indoor and outdoor
      concentrations of volatile organic compounds (VOCs) and nitrogen dioxide were
      also measured in August 1997 and February 1998. Indoor formaldehyde
      concentrations were measured 14 times (48 hrs sampling for each measurement) for
      28 days in the living room, a bedroom and the kitchen in April '97. The
      concentrations exceeded the Japanese Government's guideline value of 0.08 ppm in
      34 of the 42 (81.0%). Day to day variation in the formaldehyde concentration was
      found to be substantial, the range being between 0.073 and 0.232 ppm for the
      bedroom, for example. In June and August '97, values for 20 of 21 measurements
      exceeded the guideline, the results suggesting that indoor formaldehyde
      concentrations remain high until 7 months after the completion of construction.
      There were positive correlations between the formaldehyde concentrations in the
      living room and the kitchen and personal exposure levels to formaldehyde, the
      result indicating a direct influence of the home environment. The formaldehyde
      concentration in the living room also exhibited a positive correlation with the
      room temperature. Natural ventilation by opening windows was found to be
      effective for decreasing the concentration of formaldehyde in the indoor air.
      Indoor VOC concentrations decreased rapidly after the completion of construction
      except for that of toluene, which was higher than the outdoor concentration even
      after 7 months. Indoor concentrations of all of the VOCs were, however, found to
      be almost the same as those outdoor at the 13 month time point. Indoor nitrogen
      dioxide concentrations measured in the bedroom in winter (February '98) exceeded
      the Environmental Air Quality Standard in Japan, this result being considered due
      to use of an oil fan heater. These data suggest that personal exposure levels to
      formaldehyde and nitrogen dioxide are high in newly constructed private homes in
      Japan. In order to avoid prolonged exposure to high concentrations of indoor air
      pollutants, it is considered very important to take measures such as of use
      building materials with low formaldehyde emissions and to discontinue the use of
      oil fan heaters.

PMID- 11974925
TI  - [The policy for tobacco in work place].

PMID- 11974926
TI  - [Childcare problems in mothers with twins as compared with children born singly].
AB  - PURPOSE: The purpose of this survey was to study childcare problems in the
      families with twins as compared with singletons. METHODS: The subjects were 234
      mothers of twins and 200 mothers of singletons, all born after 1994. RESULTS: 1.
      Mothers of twins showed significantly higher anxiety during pregnancy compared
      with those having singletons. There was no significant difference in prevalence
      of anxiety for infant health between the two groups, but the mothers of twins
      showed significant higher rate for childcare after delivery, economy, or
      childcare of other brothers and sisters. 2. Mothers who felt shortage of time for
      childcare were more frequent in the twin group than in the singleton group. 3.
      Mothers of twins showed significant more severe fatigue (physical and mental) as
      compared with those having singletons. They also reported significantly poorer
      sleeping conditions. In particular, the average sleeping time for mothers of
      twins was 6.54 hours a day, while for those of singletons, it was 7.32 hours. 4.
      Mothers of twins who did not receive assistance from fathers for childcare
      reported more severe physical and mental fatigue than those of twins who were
      given such help. CONCLUSION: This study indicated a tendency for mothers of twins
      to show more severe fatigue, poorer sleeping condition and a greater shortage of
      time for childcare as compared with those having singletons.

PMID- 11974927
TI  - [WHO's Framework Convention on Tobacco Control potential impact on tobacco
      control in Japan].
AB  - OBJECTIVE: The objective of the paper are to introduce the current global tobacco
      control measures undertaken by WHO and other international organizations, and to
      describe the impact on domestic tobacco control in Japan. METHODS: Publications
      and documents, mainly for WHO, were reviewed especially with reference to the
      Framework Convention on Tobacco Control (FCTC). RESULTS: WHO has been promotion
      comprehensive tobacco control globally as well as regionally in order to assist
      and promote its national health policy. In 1998, WHO established the Tobacco Free
      Initiative (TFI) to take action against the growing health impact of tobacco
      consumption around the world. WHO has also been proposing the FCTC, the first
      international convention in the health field, which includes, for example,
      restrictions on advertisement, selling to, or buying from persons aged under 18.
      Currently, the FCTC is being negotiated by governments and is expected to be
      ratified before May 2003. WHO is also working together with other international
      organizations, such as the World Bank, in synchronizing its global tobacco
      control policy. DISCUSSION AND CONCLUSIONS: "Smoking and health" is, without
      doubt, the most significant public health problem internationally and
      domestically. However, tobacco control tends to be less strict in Japan than in
      other developed countries. Even among health personnel in Japan, the health
      impact is still underestimated, thus its control remains partial. Accelerated
      public health campaigns against tobacco and health promotion activities are
      greatly needed. These could be carried out more effectively in the broad context
      of promotion of the FCTC.

PMID- 11974928
TI  - [Gastroenterological diseases in the aged--from the standpoint of surgery].

PMID- 11974929
TI  - [Molecular physiology of olfaction].

PMID- 11974930
TI  - [A perspective in gerontology in the 21st century].

PMID- 11974931
TI  - [A prospect of biomedical gerontology].

PMID- 11974932
TI  - [Constituents of successful aging].

PMID- 11974933
TI  - [Maintenance and management of oral health care in geriatric dentistry].

PMID- 11974935
TI  - [Problem and development of medical care for aged people in 21st century].

PMID- 11974936
TI  - [Perspectives of geriatric medicine in Japan].

PMID- 11974934
TI  - [To learn from aging phenomena--mental disease and aging].

PMID- 11974937
TI  - [Studies on aging in the 21st century--interventions in physiological aging].

PMID- 11974938
TI  - [Will Alzheimer's disease be conquered in the 21st century?].

PMID- 11974939
TI  - [Long-term care for the elderly in the 21st century].

PMID- 11974940
TI  - [The future of social work practice for the elderly].

PMID- 11974941
TI  - [Fluctuation of the fibrosis markers with aging].
AB  - Actual age and biological age are not always proportional. To find out indices of
      aging, other than actual age, we investigated relationship between aging and four
      hepatic fibrosis markers: hyaluronates, type IV collagen, type IV collagen 7s and
      P III P. The subject of this study were 78 patients of inpatients and outpatients
      of our hospital. They were divided into four groups of very elderly (over 80-year
      old), elderly (70-79-year-old), non-elderly (50-69-year-old), and non-elderly (20
      49-year-old), and these four groups were compared. The results were as follows:
      regarding hyaluronates value were 86.3 +/- 46.7 ng/ml in the patients in the very
      elderly group, 58.9 +/- 37.4 ng/ml in the elderly group, 48.7 +/- 71.9 ng/ml in
      patients aged between 50 and 69 years old, and 22.6 +/- 26.1 ng/ml in patients
      aged between 20 and 49 years old. Regarding type IV collagen value were 134.6 +/-
      27.8 ng/ml in the very elderly group, 131.1 +/- 46.5 ng/ml in the elderly group,
      135.1 +/- 102.1 ng/ml in patients aged between 50 and 69 years old and 92.8 +/-
      21.8 ng/ml in patients aged between 20 and 49 years old. Type IV collagen 7s
      value were 4.4 +/- 0.9 ng/ml in the very elderly group, 4.4 +/- 0.6 ng/ml in the
      elderly group, 4.8 +/- 1.6 ng/ml in patients of between 50 and 69 years old, and
      4.3 +/- 0.6 ng/ml in patients between 20 and 49 years old. P III P value were
      0.70 +/- 0.31 U/ml in the very elderly group, 0.64 +/- 0.34 U/ml in the elderly
      group, 0.59 +/- 0.43 U/ml in patients aged between 50 and 69 years old, and 0.46
      +/- 0.14 U/ml in patients aged between 20 and 49 years old. The results indicated
      that three markers: hyaluronates, type IV collagen, P III P increased with the
      aging. Especially, hyaluronates were remarkably increased. Next, we studied 159
      patients (78 patients added to 81 patients who visited our hospital for health
      checkup), and investigated the fluctuation of hyaluronate values by the aging.
      The results showed a definite increase of hyaluronate values with age. A
      correlation was recognized between ages and hyaluronate values (correlation
      coefficient: r = 0.64, p < 0.001). Furthermore we investigated effect on aging of
      various items including fibrosis markers, immunoglobulin or serum albumin by
      using multiple factor analysis, and found that hyaluronates influenced most
      strongly on aging (p < 0.0002, p < 0.00002). Thus, hyaluronates could be
      considered to be an index other than actual ages to evaluate progress of aging.

PMID- 11974942
TI  - [Efficacy and safety of combination therapy with losartan and hydrochlorothiazide
      in elderly hypertension].
AB  - We examined the effect and safety of combination therapy with low-dose diuretics
      (hydrochlorothiazide: HCTZ) and angiotensin II receptor antagonist (losartan) in
      elderly cases of hypertension, using ambulatory blood pressure monitoring (ABPM).
      Elderly hypertensive patients (mean age 75 +/- 2 years) were treated with either
      losartan (25-50 mg/day) or HCTZ (12.5 mg/day) for at least 4 weeks, and then 24
      hour blood pressure (BP) was measured by ABPM. Combination therapy with addition
      of other drug was initiated in 14 patients whose 24-hour systolic BP or daytime
      systolic BP was over 140 mmHg (160 mmHg for the patients of 80 years or older).
      After 4 weeks of the combination therapy, ABPM was repeated. Blood cell count and
      blood chemistry were also done before and after initiation of combination
      therapy. In the losartan-preceding group (n = 9), the combination therapy with
      HCTZ reduced 24-hour BP by 19.3 +/- 2.3/6.6 +/- 2.3 mmHg. Similarly, daytime and
      nighttime BP decreased by 21.4 +/- 4/8.4 +/- 2.8 mmHg and 15.2 +/- 4/4.2 +/- 2.4
      mmHg, respectively. In the HCTZ-preceding group, the combination with losartan
      also decreased 24-hour BP by 12.2 +/- 4.8/3.4 +/- 1.4 mmHg. The decreases of
      daytime and nighttime BP were 13.8 +/- 6.6/4 +/- 1.1 mmHg and 10 +/- 4.7/3 +/-
      2.4 mmHg, respectively. Heart rate did not change with combination therapy in the
      losartan-preceding group, while heart rate during daytime tended to decrease by
      addition of losartan in the HCTZ-preceding group (3.8 +/- 1.7/min). Serum
      electrolytes, uric acid, lipids, renal function and body weight did not change
      during the study period. Thus, combination therapy of
      losartan/hydrochlorothiazide seems useful in the treatment of elderly
      hypertension, showing additive BP lowering effect without metabolic adverse
      effects.

PMID- 11974943
TI  - [Effects of carvedilol on the hemodynamics and its tolerance in elderly
      patients].
AB  - Clinical trials have shown that beta-blockers can produce symptomatic improvement
      and decrease the risk of death in chronic heart failure patients. However, the
      side effects of beta-blockers including worsening heart failure, AV-block,
      contracting peripheral vessels and unfavorable effects on glucose and cholesterol
      metabolism tend to make physicians hesitate to prescribe beta-blockers for
      elderly patients. Carvedilol is a novel non-selective beta-blocker without
      intrinsic sympathomimetic activity (ISA) and has vasodilating effect through
      blocking alpha 1 receptor. We examined the effects of carvedilol on cardiac
      parameters in order to clarify whether beta-blocker may affect left ventricular
      function in elderly Japanese patients with hypertension, angina pectoris, or
      both. We examined the hemodynamic effect of carvedilol in 16 patients with
      hypertension, angina patients or both, aged 65 and over (75.5 +/- 5.6 y.o.).
      After 12 weeks treatment with 10-20 mg daily oral administration,
      echocardiography was performed and hemodynamic parameters were calculated to
      evaluate their cardiac functions. Blood pressure was significantly decreased,
      especially in systolic pressure (163.8/87.6 +/- 15.6/11.2 mmHg to 141.6/76.9 +/-
      16.6/11.7 mmHg, p < 0.001/p < 0.01, respectively). Ejection fraction increase
      (65.8 +/- 11.8% to 71.2 +/- 11.4%, p < 0.05) accompanied heart rate decrease
      (72.0 +/- 16.1 bpm to 63.9 +/- 11.4 bpm, p < 0.05). Carvedilol increased ejection
      fraction and decreased blood pressure safely in elderly patients with
      hypertension, angina pectoris, or both. Taking the condition of each patient into
      consideration, alpha-beta-blocker can be beneficial in elder patients.

PMID- 11974944
TI  - [Effect of elapsed time after standing up on orthostatic blood pressure change in
      the elderly].
AB  - The effect of time elapsed after standing on the orthostatic change in blood
      pressure was investigated. The study subjects were recruited from 237 community
      dwelling elderly residents free from any history of cardiovascular disease and
      not on medication. Basal blood pressure was determined by averaging two
      determinations of supine blood pressure measured with an automatic oscillometric
      blood pressure recorder after resting for more than 10 minutes. Orthostatic
      change in systolic blood pressure (SBP) was determined as more than a 10%
      increase or decrease in SBP after standing. In the total population, maximum
      change in SBP was observed at 1 minute after standing-up. However, 8.4% and 7.2%
      of subjects showed abnormal increase or decrease in SBP only after 3 minutes.
      These results suggests that orthostatic dysregulation of blood pressure could be
      evaluated by measuring at 1 minute after standing up. However, if abnormal
      variation of blood pressure was not observed at 1 minute after standing up,
      repeated measurement at 3 minutes would be necessary.

PMID- 11974945
TI  - [Relationship between lifestyle activities and physical functions in elderly
      persons utilizing care facilities].
AB  - The purpose of this study was to examine the relationship between outdoor
      activity areas and physical functions such as muscle strength, postural balance,
      gait function, and to identify the physical functions related to accomplishment
      of outdoor activity in elderly persons utilizing outpatient rehabilitation
      facilities. Furthermore, we investigated the relationship among physical, social
      and intellectual activities and physical functions. The subjects were 265 elderly
      persons (average age: 80.3 +/- 7.0). They were classified into the indoor
      activity group, neighborhood outdoor-activity group and long-distance outdoor
      activity group, and functional differences among the three groups were examined.
      The Barthel index, one-leg standing time, timed up-and-go test and performance
      oriented mobility assessment were significantly different among the three groups.
      These results suggested that physical functions have a close relationship with
      extension of the activity area. Based on 95% confidence intervals, elderly
      subjects with more than 95 points on the Barthel index seemed able to do
      neighborhood outdoor activities. Those who can finish timed up-and-go test in
      less than 18 seconds, and obtain 26 points in performance-oriented mobility
      assessment may be able to do long-distance outdoor-activities using a bus.
      Furthermore, it was found that physical function was largely affected by physical
      activity such as exercise habituation and house keeping. In conclusion the
      difference of the activity area as well as extended activities of ADL influenced
      the physical function, which was critical to prevent functional decline in
      elderly persons.

PMID- 11974946
TI  - [Effect of an inhaled beta 2-adrenergic agent on pulmonary function and quality
      of life in elderly patients with chronic obstructive pulmonary disease].
AB  - We tested the effects of inhaled beta 2-adrenergic drug on the physiologic
      function of the respiratory system and quality of life (QOL) in elderly patients
      with chronic obstructive pulmonary disease (COPD). We measured the pulmonary
      function, static respiratory pressures, and ventilation during exercise, before
      and after inhalation of the beta 2-adrenergic drug, fenoterol bromide (FB) in 12
      male COPD patients (mean age 82.1 +/- 0.6 years old), QOL was measured with a St
      George's Respiratory Questionnaire (SGRQ) in the patients. Forced expiratory
      volume in one second was increased by the inhalation of FB in the patients,
      whereas the ratio of residual volume to total lung capacity was decreased by the
      inhalation. Maximum inspiratory pressure was significantly increased after the
      inhalation of FB. Dyspnea sensation during exercise assessed by the Borg scale
      was reduced by the inhalation of FB. The scores on SGRQ were improved by one
      month treatment with FB. These results indicate that treatment with FB is
      effective for both physiological function of the respiratory system and several
      aspects of QOL in elderly patients with COPD.

PMID- 11974947
TI  - [An elderly case of microscopic polyangiitis following bronchial asthma].
AB  - A 78-year-old woman who had bronchial asthma for 15 years developed dysesthesia,
      neuralgia, muscle weakness and atrophy in both feet and her left hand.
      Prednisolone (maximum dose 80 mg) was not effective, and she displayed gait
      disturbance. Laboratory findings showed leukocytosis (neutrophils dominant),
      renal dysfunction, elevation of CRP and positive P-ANCA. Biopsy revealed
      vasculitis, and reduced density of myelinated fibers. Although steroid pulse
      therapy improved neuralgia and renal dysfunction, severe disability of motor
      function and sensory disturbance still remained. Vasculitis syndrome following
      bronchial asthma indicated Churg-Strauss syndrome (CSS), while severe renal
      dysfunction and lack of eosinophilia were symptoms compatible with microscopic
      polyangiitis (MPA). The present case showed properties of both MPA and CSS.

PMID- 11974948
TI  - [Maintenance and improvement of quality of life among elderly patients using a
      pet-type robot].
AB  - There have been reports of cases in which quality of life and loneliness of
      elderly people have been affected by interaction with the pet-type robot AIBO. In
      the present comparison between first and 20th sessions of activity with the pet
      type robot, statistically significant improvements were observed in speech,
      emotional words and satisfaction index. The AKO loneliness scale value was 3.33
      at the first session, and was 1.00 at the 20th session (statistically significant
      decrease). In a comparison of health-related QOL before and after interaction
      with AIBO, using the SF-36 survey, role function (RP) was statistically higher at
      the 20th session than at the first session. Evaluation by CgA, a mental stress
      index, showed a statistically significant decrease as the number of AIBO sessions
      increased. Case 1: The patient was a 68-year-old woman with chronic rheumatoid
      arthritis. Her AKO loneliness scale value was 4 on the first session and 1 on the
      20th session. She said, "I do not think about anything while playing with the pet
      type robot. It heals my mind." Case 2: The patient was a 74-year-old woman with
      cervical osteochondrosis. Her AKO loneliness scale value was 5 on the first
      session and 2 on the 20th session. She said, "The first time, I didn't like
      playing with the robot because I was depressed. After I had played with the robot
      several times, I felt good." Case 3: The patient was an 84-year-old man with
      cerebral apoplexy sequelae. His AKO loneliness scale value was 6 on the first
      session and 1 on the 20th session. He sang with the robot occasionally. The
      amount of conversation between him and his children greatly increased. Unlike
      animals, a pet robot does not carry the risk of bacterial infection. The present
      results suggest the possibility of using robots as a substitute for animal
      assisted therapy and other psychosocial therapy in aseptic rooms, ICUs,
      children's wards, and special care wards for patients with dementia.

PMID- 11974949
TI  - [Two cases of atherosclerotic renal artery stenosis treated by percutaneous
      transluminal renal angioplasty and intravascular stent placement, leading to
      improvement of hypertension and renal function].
AB  - We describe here two cases of renal artery stenosis(RAS) caused by
      atherosclerosis. Both patients were treated by percutaneous transluminal renal
      angioplasty(PTRA) and stent placement, leading to the improvement of renal
      function as well as hypertension. The two patients were a 75-year-old male(case
      1) and a 56-year-old male(case 2), who both showed mild proteinuria, renal
      dysfunction, and refractory hypertension. Case 1 showed a unilateral ostial
      stenosis in the left main renal artery. On the other hand, case 2 showed an
      ostial stenosis in the left renal artery and a widespread narrowing in the right
      renal artery. After evaluation of the lesions by renal Doppler sonography,
      renogram, magnetic resonance signal intensity, and magnetic resonance
      angiography(MRA), each stenosis was treated by balloon angioplasty and
      intravascular stent placement without any major complications. Thereafter, in
      addition to hypertension, renal function also ameliorated significantly, and has
      remained stable for more than 12 months. Non-invasive screening tests and
      appropriate therapy for renovascular lesion should be considered in the case of
      elderly patients with refractory hypertension and progressive renal dysfunction,
      since ischemic nephropathy is increasing as a common cause of end stage renal
      disease and is showing favorable outcomes of revascularization.

PMID- 11974950
TI  - [Complete remission of minimal change nephrotic syndrome with type 2 diabetes
      mellitus treated by microemulsion formulation of cyclosporin and fluvastatin].
AB  - A microemulsion formulation of cyclosporin (Neoral) has been developed to
      overcome the problems of poor and variable absorption of cyclosporin. Neoral is a
      potent immunosuppressive agent that is highly bound in the plasma. It has been
      proposed that low-density lipoprotein (LDL) delivers cyclosporin (CsA) to T
      lymphocytes via the LDL receptor pathway, where it produces its therapeutic
      effects. Herein, we report a case of minimal change nephrotic syndrome with type
      2 diabetes mellitus treated by Neoral and fluvastatin. A 65-year-old male with a
      10-year history of type 2 diabetes mellitus suddenly developed nephrotic
      syndrome. The potential causative drugs, such as NSAIDs and antibiotics, had not
      been administered. The laboratory findings were as follows: proteinuria 23 g/day,
      serum albumin 1.9 g/dl, total cholesterol 629 mg/dl, LDL-Cho 1,930 mg/dl. Renal
      biopsy was normal on light microscopy, and immunofluorescence demonstrated no
      staining. Due to the risk of deterioration of diabetes by administering
      prednisolone, he was given Neoral at 2.0 mg/kg/day. He was also given fluvastatin
      (40 mg/day) for hyperlipidemia after the renal biopsy. At four weeks after the
      start of Neoral and fluvastatin, his nephrosis continued, but his LDL-Cho and
      total cholesterol decreased. At six weeks after treatment, proteinuria gradually
      reduced. At eight weeks after treatment, the proteinuria had disappeared.
      Nephrotic syndrome is often associated with abnormal lipid metabolism, and many
      patients with nephrotic syndrome show high levels of LDL-Cho. It has been
      reported recently that LDL apheresis is effective against nephrotic syndrome.
      However, in the present case, it can be speculated that the improvement of
      hyperlipidemia by fluvastatin probably augmented the effect of Neoral, presumably
      through the increased cellular uptake of Neoral. This suggests that fluvastatin
      may be considered as the treatment of choice for the disturbed lipoprotein
      profile in patients with nephrotic syndrome.

PMID- 11974952
TI  - [Acute renal failure].

PMID- 11974951
TI  - [Guidelines for the management of rapidly progressive glomerulonephritis].

PMID- 11974953
TI  - Health care funding in the Australian Capital Territory: from hospital to
      community.
AB  - This paper presents an outline of the socio-demographic features of the
      Australian Capital Territory (the ACT) and of its health care system. I describe
      how health care resources are allocated in the government sector, present a more
      detailed description of the way that hospital services are purchased, and
      summarise the government's policy directions for health. I argue that the main
      directions are sensible, and particularly those that support more integrated care
      that is largely based in the community. There appear to be no major weaknesses in
      the budget-share output-based funding model used in the purchase of hospital
      services, although the rationale for some of the components might be clarified.
      In total, the ACT government appears to be on the right track. However, I argue
      that more rapid progress might be possible if there were greater collaboration
      between the Territory health authority and the relatively powerful private
      medical profession.

PMID- 11974954
TI  - Hospital services in Tasmania.

PMID- 11974955
TI  - Funding of South Australian public hospitals.
AB  - Since the 1994-95 financial year, inpatient episodes of care in South Australian
      public hospitals have been funded according to their casemix. This paper
      describes the current funding system, sets it in some context and examines what
      can be established about hospital performance.

PMID- 11974956
TI  - Hospital services and casemix in Western Australia.
AB  - The Health Department of WA currently operates as a single integrated funder and
      purchaser of health services for the State. Health Service Agreements defining
      the level of health provision are negotiated with the various health services in
      WA. During the latter part of the 1990s, the funding of public hospitals for
      acute inpatient care moved away from a historical basis to output-based funding
      using a casemix approach based on Diagnosis Related Groups (DRGs). Other hospital
      services are still mainly purchased using historical funding levels, negotiated
      block funding or bedday payments, with output-based funding mechanisms under
      investigation. WA has developed its own approach to classifying admitted patients
      that recognises differences in complexity of care among episodes grouped to the
      same DRG. WA also has a unique cost estimation model for calculating DRG cost
      weights, which is based on a linear estimate of the relationship between nights
      of stay in hospital and the cost of hospital care for each DRG. Another emerging
      trend in the provision of public hospital services in WA has been the greater
      involvement of the private sector through the contracting of private providers to
      operate public hospitals. While no close examination has been undertaken of the
      outcomes of these changes in terms of their effect on efficiency or other
      relevant indicators of hospital performance, current purchasing arrangements are
      being reviewed following recommendations made in a report by the Health
      Administrative Review Committee. No decision has yet been made as to future
      changes to the funding policy of WA public hospitals.

PMID- 11974957
TI  - Funding of Northern Territory public hospitals.
AB  - The Northern Territory is Australia's third largest jurisdiction by land mass but
      it is the smallest by population. By proportion it accommodates the largest
      number of Aboriginal people who suffer the greatest burden of disease with high
      morbidity, mortality, admission rates and lengths of stay. Output based funding
      by DRG is based on the "typical" Australian population which is not that of the
      Northern Territory. The NT has had to significantly modify its approach to
      funding to meet the needs of its population. The current funding method based on
      detailed analyses of clinical data with small numbers may be inappropriate where
      simpler methods tailored to the NT population could suffice.

PMID- 11974958
TI  - The funding of private hospitals in Australia.
AB  - Private hospitals are an essential component of Australia's complex mix of public
      and private health funding and provision. Private hospitals account for 34.3 per
      cent of all hospital separations, and over half (56.2%) of all same-day
      separations. The revenue (funding) of the sector approached $4 billion by
      1998/99, and as a result of its recent rapid growth capital expenditure in the
      sector was nearly $550 million in the same year. Private casemix of private
      hospitals is distinctive, and characterised by a high proportion of surgical
      procedures in general (48.1 per cent), and more than a majority of all services
      in such areas as rehabilitation, orthopaedics (shoulder, knee, spinal fusion, and
      hand surgery), alcohol disorders, same day colonoscopy and sleep disorders. This
      chapter synthesizes data from a multitude of sources to produce a comprehensive
      picture of Australia's private hospital sector and its funding. It examines the
      funding (revenue) sources of private hospitals, and considers how and why private
      hospitals approach the issue of funding from a different perspective than their
      public sector colleagues. To illustrate how Australian private hospitals approach
      revenue (funding) strategically, a series of indicative types of hospitals is
      explored.

PMID- 11974959
TI  - Australian hospital services: an overview.
AB  - Hospital services in Australia are provided by public hospitals (about 75% of
      hospitals, two-thirds of separations) and private hospitals (the balance).
      Australians use about one bed day per person per year, with an admission rate of
      about 300 admissions per thousand population per annum. Provision rates for
      public hospitals have declined significantly (by 40%) over the last 20 years but
      separation rates have increased. Average length of stay for overnight patients
      has been stable but, because the proportion of same day patients has increased
      dramatically, overall length of stay has declined from around seven days in the
      mid 1980s to around four days in the late 1990s. Overall, the Commonwealth and
      state governments each meet about half the costs of public hospital care, private
      health insurance meets about two-thirds of the costs of private hospitals.

PMID- 11974960
TI  - Health care funding in New South Wales: from health care needs to hospital
      outputs.
AB  - This paper summarises the structure of the State's health care system, and then
      focuses on the main processes of resource allocation: needs-based funding of 17
      Area Health Services, and output-based funding of specific service providers. The
      general model is widely accepted by informed observers to be fundamentally sound.
      In particular, the resource distribution formula whereby needs-based allocations
      are made is a largely valid model that has been progressively refined over
      fifteen years and is probably as good as any in the world. I conclude that the
      recent decision to require Area Health Services to use a common framework for out
      put-based funding was long overdue, and that many of its features represent best
      practice. However, I argue that more should be done to refine some of the details
      and that NSW Health might need to give more consideration to ideas that have been
      tested and evaluated in other health care systems.

PMID- 11974961
TI  - Funding Victoria's public hospitals: the casemix policy of 2000-2001.
AB  - On 1 July 1993 Victoria became the first Australian state to use casemix
      information to set budgets for its public hospitals commencing with casemix
      funding for inpatient services. Victoria's casemix funding approach now embraces
      inpatient, outpatient and rehabilitation services.

PMID- 11974962
TI  - Hospital funding and services in Queensland.
AB  - The Queensland health sector has been characterised as unique. The population has
      traditionally relied on the public sector to provide necessary hospital and other
      health services across the vast distances that make up the state, although there
      is a strong non-government sector also. More recently, and over the last 5-6
      years stability and drive at the management level in the public sector has
      supported reform and progress, consistent with the national agenda. The
      Queensland reputation of cost efficiency and effectiveness in service delivery
      and outputs to meet national standards continues as this Chapter demonstrates.

PMID- 11974963
TI  - [Occult fractures of the carpal navicular. Detection by quantitative
      radioscintigraphy. Social and medico-legal repercussions].
AB  - Fractures of the scaphoid of the wrist are not easily diagnosed and when they are
      eventually recognized due to late complications, the prognosis is much poorer
      than it would have been at injury. Medical negligence and poorly-performed or
      interpreted x-rays are frequently cited as reasons for non-diagnosis. Often these
      fractures are trabecular, so-called occult, and they cannot be seen on a
      conventional exam, even if well-performed. Tomography and tomodensitometry have
      yielded poor results. Quantitative radioscintigraphy (QRS), the exam we are
      proposing, is a modification of scintigraphy, which is a very sensitive exam
      (100%) but has little specificity. The first step in QRS is to quantify the
      fixation of the tracer on the injured side and compare it to that of the
      uninjured side. If the injured side fixation is double that of the uninjured
      side, a fracture (often scaphoid) is present. MRI is our reference. In the second
      step in QRS, a computer-assisted fusion is made of the scintigraphic image and
      the x-ray (quantitative scintigraphy has the same diagnostic value as MRI). The
      center of the fracture is localized, thus yielding a specificity of nearly 100%
      for this exam. Out of a prospective series of 154 patients who had a conventional
      examination: 41% were diagnosed to have a scaphoid fracture using QSR, therefore
      a number higher than supposed. Rare carpal fractures were also detected. The cost
      of this exam is low. The exam climinates non-diagnosed fractures which can lead
      to non-union and arthrosis. Due to the frequency of carpal trauma, this exam
      should have a significant effect on the individual, on social security costs and
      litigations.

PMID- 11974964
TI  - [Combined neuronal toxicity of bilirubin and hypoxia. Study of cultured rat
      neurons].
AB  - Clinical observations suggest that bilirubin encephalopathy is often seen in
      newborn infants presenting not only with hyperbilirubinemia but also with
      alterations in oxygen transport like in severe anaemia. Since bilirubin and
      hypoxia have been shown to be detrimental to the central nervous system, the
      present study was designed to test the additional effects of the two insults on
      the outcome of cultured neurons from the forebrain of 14 day-old embryos. After 6
      days in vitro, neurons were exposed either to bilirubin (0.5 microM) or to
      bilirubin and hypoxia for 6 hours. Thereafter, cells were reoxygenated for 96
      hours in standard conditions. Control cells were kept in normoxia. Cell viability
      was assessed by the methyltetrazolium method. Cell death (apoptosis or necrosis)
      was characterized by fluorescent nuclear staining with DAPI. Rates of protein
      synthesis and energy metabolism in neurons were measured by [3H]leucine and [3H]2
      deoxyglucose incorporation, respectively. Data are reported as percentages of
      change as compared to controls. Each experiment involved 5 to 10 dishes per time
      point and was repeated 2 to 4 times. RESULTS: Bilirubin reduced cell viability by
      24.5% vs controls (p < 0.001) at 96 h while 16% of the neurons exhibited
      morphological features of apoptosis (p < 0.001). The combination of hypoxia with
      bilirubin induced a 34% decrease in cell viability (p < 0.001) and the percentage
      of apoptotic cells was higher than after the exposure to hypoxia or to bilirubin
      alone. The rate of protein synthesis increased significantly in all experimental
      conditions as early as 1 h after the onset of the insult and at 48 h post
      reoxygenation. It increased again at 72 h in the cells exposed to bilirubin or to
      bilirubin and hypoxia. These sequential changes in synthesis of specific proteins
      seem to be involved in delayed neuronal death. Bilirubin decreased significantly
      [3H]2-deoxyglucose incorporation at 24 h while it increased when the neurons were
      exposed to both bilirubin and hypoxia (+60%, p < 0.001) and decreased thereafter.
      These data confirm the deleterious effects of bilirubin on neuronal viability, on
      protein synthesis and metabolic rates. The combination of bilirubin with hypoxia
      resulted in stronger detrimental effects on neurons than bilirubin alone.

PMID- 11974965
TI  - [In vitro protection of cerebral mitochondrial function by E-resveratrol in
      anoxia followed by re-oxygenation].
AB  - Using an experimental model of anoxia-reoxygenation applied to suspensions of
      mitochondria isolated from rat cortex, we have searched the effects of
      resveratrol added to the suspension or previously injected to rats from which
      mitochondria were extracted. With this model, we observe that resveratrol
      counteracts decoupling effects induced by anoxia-reoxygenation. It also fully
      inhibits intermembrane cytochrome c release, initial step of mitochondrial
      apoptosis and blocks ATP generation which achieves it. These effects are
      concentration-dependent and take place at low concentrations. It is concluded
      that resveratrol limits or suppresses the mitochondrial deleterious effects
      promoted by anoxia followed by reoxygenation.

PMID- 11974967
TI  - [Treatment of deep vein thrombosis. Current and future questions].
AB  - Treatment of deep vein thrombosis is founded on the association of low molecular
      weight heparin and oral anticoagulant for three or six months. However efficacy
      and safety of low molecular weight heparin are not different from that of
      unfractionated heparin. Moreover measurement of anti-Xa activity does not permit
      a clear definition of therapeutic range in patients with a high hemorrhagic risk.
      Oral anticoagulant prevent recurrences of venous thrombosis, however the high
      risk of major haemorrhages limits their long term use. Pentasaccharide and
      Melagatran are news potent drugs that should deeply modify the treatment of
      venous thrombo-embolism.

PMID- 11974966
TI  - [Human onchocerciasis and "sowda" in the Republic of Yemen].
AB  - The geophysics of the north Yemen, associating a north-south directed mountainous
      fish bone (rising in more of 2,000 meters), to numerous rivers or "wadis" is
      convenient to the development of simulium shelters, main vectors for cutaneous
      filariasis to Onchocerca sp. Following several missions of bio-clinical and
      epidemiological evaluations in neighbouring villages of wadis, it has been
      possible to study different clinical aspects: one reminding the classical african
      onchocerciasis with generalized and diffused dermatitis, and, on an other hand, a
      hyperreactive dermatitis on one side of the body and associated with a collateral
      lymphatic ganglion. This disease is well known for local populations as "aswad"
      meaning "black" or "sowda". Clinically whatever the studied focus, coexists the
      two types of onchodermatitis (uni or bilateral). Yhe sowda patients are
      proportionally less numerous than those touched by the generalized type. Frequent
      eye lesions of the West African onchocerciasis are not found in sowda cases. In
      classical optical microscopy, microfilaria is morphologically indifferenciable
      between sowda and onchocerciasis clinical aspects. Skin snips were carried out on
      patients of both groups. Identification of microfilaria by molecular biology
      through the study of the DNA genome was done out of 5 skin snips. Microfilaria
      was kept dry between laminas and the DNA extracted from rehydrated microfilaria.
      DNA was intensified with specific primers of Onchocerca type (O150PCR). This
      phase was followed by hybridisation of amplification products by PCR to specific
      stains: OVS-2 for Onchocerca volvulus species, OCH for Onchocerca ochengi, PFS1
      and PSS1-BT respectively for the forest strain and the savannah strain of
      Onchocerca volvulus as described previously. We can distinguish 2 kinds of
      answers based on the clinical origin of the snip-tests: the first one concern 3
      patients with numerous dermal microfilariae but without any clinical sowda and
      corresponding to microfilaria O. volvulus type but different from the forest or
      savannah strains found in sub-Saharan Africa. The second one corresponds to 2
      patients with less than 5 microfilaria in their snip-test. They show the typical
      clinical picture of sowda. They are identified as microfilaria type Onchocerca
      but they do not belong to species volvulus, or to species ochengi. It seems quite
      probable that the clinical picture of sowda be the result of developing
      onchocerciasis of animal origin and not identified as to day. The ivermectin,
      therapeutic of choice for African onchocerciasis in annual unique cure seems less
      effective in the coverage of sowda. In that case rehearsal of cures every 3
      months would be necessary for mass campaigns to limit the transmission of this
      filariasis.

PMID- 11974968
TI  - [Morbid obesity, public health problem: laparoscopic surgical treatment].
AB  - Morbid obesity, commonly defined as a condition in which the weight exceed twice
      the ideal body weight, is a major public health concern, widely unrecognized in
      France whereas causing 55,000 deaths per year to compare to 8,000 deaths per year
      by traffic accidents. Its pathogenesis is discussed even if much attention in
      recent years has centered on genetic causes since the identification of the ob
      gene and its protein product leptin. Due to the long term failure of medical
      treatments, the advent of laparoscopy had disrupted therapeutic and carried on
      exponential development of laparoscopic operations mainly by gastric banding
      using an adjustable ring not without complications. It is why we have performed a
      prospective study by laparoscopy in 100 patients comparing 3 operations with the
      aim that each indication could be adapted to the alimentary behaviour. The short
      term results are extremely favourable and comparable to international literature
      data. Moreover, the study is a plea for a multidisciplinary approach of morbid
      obesity and a core for a public health action.

PMID- 11974969
TI  - [Nutritional management of highly trained child athletes].
AB  - The nutritional care of children and adolescents who practice sports more than 10
      h/weeks is an important task. Advices must be adapted to the child according to
      his sport, his age, his gender, his weight and to the intensity of his physical
      activity; they intend to provide him, in addition to his basal requirements,
      those due to the extra expenses of water, energy, minerals and vitamins. The aim
      of the physician is to allow these children an adequate growth and the normal
      development of puberty, to prevent deficiencies and to concur with other
      specialists to the prevention of muscle, joint and bone wounds who can affect a
      growing organism. This ambitious program relies on a thorough knowledge in
      pediatrics, nutrition and sport in order to adapt the advice to the specific way
      of life of the child, taking into account the schedules of school time, training
      and competition. Such an approach needs that every child undergoes a medical
      examination 3-4 times/year, a biological check up at least once a year, a careful
      follow up of growth and pubertal maturation. Every time it is possible parents
      and coaches are encouraged to attend the visit when everything is OK and even
      more when difficulties occur, whether they are due to somatic or psychological
      trouble or in case of poor performance induced discouragement. A balanced
      nutrition, an adequate counseling and an adapted follow up are essential for the
      success of athletes; they do not make champions from them but decrease the hazard
      of wounds, underperformances and make easier blossoming for children.

PMID- 11974970
TI  - [Enhancement of endogenous antioxidant defenses: a promising strategy for
      prevention of skin cancers].
AB  - There is considerable evidence that ultraviolet radiation (UV) from sunlight is
      implicated in skin carcinogenesis. So the risks of cutaneous cancer have
      increased during the last decade due to increase of sun exposure. For a long
      time, ultraviolet B radiation (UVB: 290-320 nm) have been considered to be the
      more efficient wavelength in eliciting carcinogenesis in human skin. It is today
      clear that UVA (320-400 nm), especially UVA1 (340-400 nm) also participate to
      photo carcinogenesis. One of molecular mechanisms in the biological effects of UV
      is the induction of reactive oxygen species (ROS) directly or through endogenous
      photosensitization reactions. UVA radiation mainly acts via this production of
      ROS and the subsequent oxidative stress seems to play a crucial role in the
      deleterious effects of UVA. Fortunately, the skin possesses a wide range of
      interlinked antioxidant defence mechanism to protect itself from damage by UV
      induced ROS. However, the capacity of these systems is not unlimited; they can be
      overwhelmed by excessive exposure to UV and then ROS can reach damaging levels.
      An interesting strategy to provide photoprotection would be to support or enhance
      one or more of these endogenous systems. In our experiments, we have evaluated
      the protective effect of glutathion, selenium and zinc, three compounds playing a
      pivotal role in the cellular defence against oxidative damage. We have irradiated
      both by UVA1 and UVB culture of human normal skin fibroblasts or of spontaneously
      immortalised human keratinocyte cell line Hacat. Before irradiation, treated
      cells were submitted to zinc deprivation by a diffusible zinc chelator, NNN' N'
      tetrakis (2-pyridylmethyl) ethylene diamine (TPEN) or supplied with zinc
      chloride, thiols (N-acetyl-cysteine; N-acetyl-homocysteine-thiolactone,
      L2oxothiozolidine-4 carboxylate) selenium as sodium selenite. The cell viability
      was measured using the adhesion-proliferation method or a tetrazolium
      colorimetric assay. The damages induced to cellular membrane were appreciated by
      determination of thiobarbituric reactants (Tbars) by a fluorometric micromethod.
      Cellular DNA damage was examined by strand break determination carried out using
      the method described by Birnboim and Jevcak and by the Comet assay. Our results
      show that: UVA1 have a main part in cytotoxic effect of UVA and this effect is
      linked to ROS; thiols and selenium protect cells against UVA radiation with a
      synergic interaction and this protection acts though an increase in glutathion
      peroxidase activity; zinc protects against cytotoxicity of UVA and UVB and
      against UVB induced DNA damages; above all, DNA damages induced by UVA or UVB are
      significantly prevented by thiol molecules, selenium and zinc. As DNA damages
      have a main place in photocarcinogenesis, our results point out the potential
      interest of a photoprotection based on the support of endogenous antioxidant
      system. The research of new ways for photoprotection is indeed a necessity
      because sunscreens did not give convincing evidences of efficacy in preventing
      skin cancers.

PMID- 11974972
TI  - Application of a dual channel peroneal nerve stimulator in a patient with a
      "central" drop foot.
AB  - Dropped foot is a common mobility problem amongst patients after a cerebro
      vascular accident. The condition arises from paresis of the muscles that control
      the foot movement during the swing phase of gait. If the abnormal movement is not
      compensated for, it results in a significant decrease in the mobility and hence
      quality of life. Compensation for the drop foot can be achieved through the
      application of functional electrical stimulation. To date, in the clinical
      environment, the stimulation has been applied through electrodes placed on the
      skin over the common peroneal nerve, and using a single channel implant device.
      It is well known that with these techniques it is difficult to establish a
      balanced response of the foot. An implantable dual channel system for stimulation
      of the deep and superficial peroneal nerve has now been developed for patients
      with a drop foot following a stroke. By stimulation of the two branches of the
      common peroneal nerve separately it is possible to achieve a precisely balanced
      dorsal flexion and eversion of the foot. Stimulation occurs via small bipolar
      electrodes which are placed subepineural. After successful tests on animals we
      have now started the two channel peroneal nerve stimulator implantation in
      patients. The preliminary results of the first implants are presented.

PMID- 11974971
TI  - [Is an international scientific language useful? Historical perspective].
AB  - From ionian Greek, used by Hippocrates, to scientific English, some key-moments.

PMID- 11974973
TI  - Rehabilitation of hearing and communication functions in patients with NF2.
AB  - Most patients with neurofibromatosis type 2 (NF2) lose hearing either
      spontaneously or after removal of their neurofibromas. The patient may benefit
      from conventional hearing aids if, due to modern microsurgery and intraoperative
      monitoring the integrity of the cochlea and the 8th nerve is preserved. With lost
      auditory function but preserved electrical stimulibility of the 8th nerve a
      cochlear implant may be appropriate. But if the patients have no remaining 8th
      nerve to stimulate, there is no benefit from cochlear implants. Until some years
      ago, vibrotactile aids, lip-reading, and sign language have been the only
      communication modes available to these patients. With auditory brain stem
      implants it is now possible to bypass both the cochlea and the 8th nerve and to
      stimulate the cochlear nucleus directly. Stimulation of the devices produces
      useful auditory sensations in almost all patients. Testing of perceptual
      performance indicated significant benefit from the device for communication
      purposes, including sound-only sentence recognition scores and the ability to
      converse on the telephone. Also lip-reading is significantly improved with brain
      stem implants. The successful work of an auditory brainstem program center
      depends very much on the close interdisciplinary collaboration between the
      Departments of Neurosurgery and ENT-surgery. In the future new developments like
      speech processing strategies and new designed electrodes accessing the complex
      tonotopic organization of the cochlear nucleus may further improve rehabilitation
      in these patients who would have been deaf some years ago.

PMID- 11974974
TI  - Standards of neurologic-neurosurgical early rehabilitation--a concept of the
      study group neurological-neurosurgical early rehabilitation.
AB  - Neurological neurosurgical early rehabilitation (NNER) is a new important
      therapeutic link within the spectrum of neurorehabilitation. This concept was
      formulated by expert opinion of the German Task Force on NNER to define both the
      structural and process quality of rehabilitation in patients who sustained brain
      damage with sensory motor, cognitive, and neurobehavioural impairment. NNER is
      focused on improving higher nervous functions, preventing or treating secondary
      and tertiary complications and thus to recuse disabilities. This concept is based
      on interdisciplinary teamwork and needs multidisciplinary cooperation with all
      specialists involved. The progress of recovery can be measured with the aid of
      the Coma Remission Scale.

PMID- 11974975
TI  - Electrical stimulation of the sural nerve partially compensates effects of
      central fatigue.
AB  - OBJECTIVES: Depression of motor evoked potentials (MEPs) following transcranial
      magnetic stimulation (TMS) may be a sign of central motor fatigue. Abnormal
      fatigue can be observed in MS patients. We have examined whether post-exercise
      MEP depression can be compensated by application of sensory stimuli prior to TMS.
      METHODS: We studied 15 healthy volunteers (aged 21 to 28 years) who were required
      to perform an exercise protocol of ankle dorsiflexion until force fell below 66%
      of maximum force. MEPs were recorded from the right tibialis anterior muscle.
      Prior to TMS, electrical stimuli were applied to the ipsilateral sural nerve with
      an individual interstimulus interval between 50 to 80 ms. RESULTS: MEP areas
      decreased after exercise. When a sensory stimulus was administered MEPs did not
      change. DISCUSSION: We conclude that the effects of central fatigue may be--at
      least partially compensated--by application of sensory stimuli. Sensory
      stimulation (e.g. by implantation of a neurostimulator) might be a useful therapy
      for abnormal central fatigue.

PMID- 11974976
TI  - Management of upper and lower limb spasticity in neuro-rehabilitation.
AB  - This article reviews the treatment of upper and lower limb spasticity in
      neurological rehabilitation. Botulinum toxin A proved effective in several
      placebo-controlled studies reducing muscle tone, easing hand hygiene and nursing,
      improving upper limb motor functions and gait ability. The effects are reversible
      and the toxin is well tolerated. Electrical stimulation, tonic stretch post
      injection and the active use of the treated extremity are means to increase the
      effectiveness of the costly therapy. Phenol 5% is an alternative in case of
      budget constraints, but the technique is demanding and side effects are more
      frequent. Further, task-specific repetitive therapy should follow the successful
      treatment of focal spasticity in eligible patients to get the maximum profit with
      regard to disability.

PMID- 11974977
TI  - Botulinum toxin (DYSPORT) in tension-type headaches.
AB  - OBJECTIVES: Botulinum toxin type A is effective in the reduction of muscle
      tenderness and pain in many diseases associated with myofascial pain. Since
      increased muscle tension may contribute to tension-type headaches, injections of
      botulinum toxin could be of therapeutic value. METHODS/PATIENTS: Results of own
      investigations are presented, in particular a double-blind, placebo-controlled
      study with 21 patients fulfilling the International Headache Society criteria for
      tension-type hedaches. Participants were randomly assigned to verum (pericranial
      injection of 10 x 20 MU DYSPORT) or placebo condition (injection of isotonic
      saline in the same manner). RESULTS: After 4, 8, and 12 weeks no significant
      differences between placebo and verum could be observed. Nevertheless, both
      groups significantly improved. DISCUSSION: The findings strongly suggest that
      higher doses or other injection sites might be necessary to achieve therapeutic
      effects of botulinum toxin in tension-type headaches. Actually, we are
      participating in a multi-center study using 500 MU of DYSPORT. Besides dose
      finding problems, another explanation could be that peripheral mechanisms--such
      as increased pericranial muscle tension--only play a minor role in the
      pathogenesis of tension-type headaches.

PMID- 11974979
TI  - Incidence and management of complications during posttraumatic early
      rehabilitation.
AB  - Early rehabilitation after traumatic brain injury has become a worldwide accepted
      interface between intensive care medicine and rehabilitation to aim for a better
      functional outcome of the surviving patients. So each chain can only be as strong
      as its weakest link, and there is still need for well defined quality standards
      depending on the medical demands during this period of treatment. Hence we were
      interested in quantifying the complications occurring until discharge to further
      rehabilitation with special regard on severe physical handicaps and organ failure
      necessitating surgical or intensive care therapy. Our results demonstrate that
      early rehabilitation is a part of intensive care medicine with enhanced
      approaches to preserve rehabilitation potential of the brain and for coma
      stimulation.

PMID- 11974978
TI  - Early rehabilitative concepts in therapy of the comatose brain injured patients.
AB  - OBJECTIVES: To evaluate the changes of vegetative parameters and behavioural
      assessment in comatose patients after severe brain injury during the Multimodal
      Early-Onset-Stimulation (MEOS) in early rehabilitation. MATERIAL AND METHODS: We
      studied 16 predominantly male (3:1) patients, age mean 43.6 (16-77) years. Mean
      coma duration was 22.2 (8-41) days, therapy duration (MEOS) 9.8 (1-30) days. The
      initial GCS was 6.6 (3-9), KRS 5.3 (0-15). Including criteria for therapy: Severe
      head trauma, coma for at least 48 hours (GCS < 8), vegetative stability, normal
      intracranial pressure, abandon of mechanical ventilation, sedation and severe
      infections. MEOS was finished in achieving GCS > 9, follow-up investigations were
      made after 2 years. RESULTS: We identified significant changes in two vegetative
      parameters (heart/respiratory frequencies), even in deep coma (GCS 3-4). Most
      significant changes were caused by tactile and acoustic stimulation. Standardized
      behavioural assessment turned out to be particularly advisable in cases of medium
      coma (GCS 5-7). Stimulation of tactile and acoustic senses resulted mainly in
      mimical, head and eye movements. Follow-up was possible in 14 patients: One
      remained in a vegetative state (GOS 2), two exhibited severe
      neurologic/neuropsychologic deficits, depending on care (GOS 3), six substained
      major functional deficits (GOS 4), at though they were able to perform the tasks
      of daily life on their own, three patients reached GOS 5. Two returned to their
      former jobs. DISCUSSION AND CONCLUSION: The present results indicate that
      stimulation therapy should be based on a close observation of patterns of
      behaviour, and, at least in deep coma stages, involve the registration of
      vegetative parameters. It may be sensitive to identify parameters predicting a
      favourable or unfavourable outcome. Preliminary data seem to support the
      hypothesis that the absence of any response to external stimuli is indicative of
      an unfavourable outcome.

PMID- 11974980
TI  - Neuro-rehabilitation--a challenge for neurosurgeons in the century 21st concepts
      and visions of the WFNS-Committee on neurosurgical rehabilitation.
AB  - OBJECTIVES: Patients with severe brain, spinal cord and peripheral nerve lesions
      today survive surgery. This, however, is quite often achieved at the burden of
      disabilities. Neuro-rehabilitation could improve significantly patient's quality
      of life (QoL). METHODS: Formed in 1997, the WFNS Committee supports all efforts
      regarding personal and regional activities, teaching, research, recommendations,
      guidelines, and practical application to improve neurosurgeon's quality
      management within the spectrum of rehabilitation around the world. RESULTS: Neuro
      rehabilitation became part of the scientific programmes at the 11th EANS, 10th
      AANS, ICRAN 1999, and now 12th WFNS congresses. The first international
      conference on Neurosurgical Rehabilitation took place in D--Munster, 2000.
      CONCLUSIONS: The WFNS Committee can influence neurosurgeons to take over the
      challenge of neuro-rehabilitation to improve patient's outcome in respect to
      ICIDH-2 WHO classification. Delegates of all neurosurgical societies are kindly
      invited to join us.

PMID- 11974981
TI  - Early functional outcome in isolated (TBI) and combined traumatic (CTBI) brain
      injury.

PMID- 11974982
TI  - Neurological and social long-term outcome after early rehabilitation following
      traumatic brain injury. 5-year report on 240 TBI patients.
AB  - The long term courses of patients after traumatic brain injury (TBI) are
      particularly influenced by the quality of neuropsychological rehabilitation and
      social reintegration. Though we do have data from different European countries
      about the success of surgery and intensive care, we don't know much about the
      long term courses, mirrored by the patients, their relatives and local physicians
      in their domestic environment. Supported by a pilot project of the government of
      Nordrhein--Westfalia we reviewed 252 patients with different grades of TBI, which
      were treated in our department from emergency to the end of early rehabilitation.
      At least 240 files could be completed, including observations up to 5 years after
      trauma (mean 26 months). 66% of the patients suffered from severe TBI according
      to the initial Glasgow Coma Scale (GCS), 23% showed moderate and 11% mild TBI.
      After discharge from early rehabilitation and during further treatment in
      rehabilitation hospitals patients with persistent vegetative state (PVS) did not
      show a significant benefit from therapy: Only 1 patient improved to GOS 3, fatal
      courses were observed in 3 patients, 11 patients remained unchanged. Patients
      with GOS 3 at the end of early rehabilitation on the other hand could improve in
      51 cases to GOS 4 and 5. At the time of the actual investigation 32% of the
      patients reached GOS 5, 27% GOS 4. Unfavourable courses showed 21% (GOS 3), 5%
      (GOS 2) and 15% (GOS 1). Referred to the initial GCS only 16% of the severe, 27%
      of the moderate and 33% of the mild TBI could return to their former social
      activities and profession without any cuts. 145 of the total of surviving
      patients could return to their families, in the group of vegetative patients all
      except 1 patient were submitted for nursing homes. Only 58% of the patients
      practiced any kind of outpatient rehabilitation, a specialized neuropsychological
      training has been restricted to 7% of the patients. So we observe a significant
      gap between a high impact clinical medicine on one side and a deficient
      outpatient treatment on the other. At least many patients are standing alone
      after discharge from rehabilitation hospitals, resulting in prolonged stationary
      treatment with extensive costs to minimize damage from this situation. Our
      consequence for a more efficient treatment is, that we substantially need better
      programs by local administrations, insurance companies and employers for better
      and earlier reintegration to avoid isolation and unnecessary invalidation,
      especially of those patients with the best medical prognosis.

PMID- 11974983
TI  - Requirements of team effectiveness in neurosurgical rehabilitation.
AB  - The purpose of this article is to stress the importance of working with
      interdisciplinary teams in neurorehabilitation and describe requirements of team
      effectiveness. It is not sufficient to focus only on different impairments
      associated with brain injury and offer individuals a variety of therapy. The
      essential aspect in neurorehabilitation is the integration of disciplines and
      consistent goal setting to regard individual patient's needs. Interdisciplinary
      teams benefit from a leader qualified for neuroscience, neurorehabilitation,
      clinical neuropsychology and psychotherapy. A good structural organization of the
      team, notice of basic communication rules, understanding typical group dynamics
      and stressors of interdisciplinary teams, conflict management and a definite
      decision making increase productive interdisciplinary working and enable the team
      to continue to mature. Further empirical research is necessary to support the
      effectiveness of interdisciplinary teams as an important variable in the
      evaluation of rehabilitation outcome and quality control.

PMID- 11974984
TI  - Merging pathways: music therapy in neurosurgical rehabilitation.
AB  - Relatively few departments of Music Therapy are found within neurosurgical
      rehabilitation clinics. In institutions where these departments exist, music
      therapy has become an integral part of multi-professional treatment and research
      activities (Gilbertson 1999). The diverse intervention strategies in Music
      Therapy focus upon auditory, motor, visual, cognitive and affective processing
      which are all involved in receptive and expressive musical behaviour and which
      affect related non-musical behaviour. A clear differentiation is made between
      primary and adjunct therapy roles. The related fields of neuromusicology,
      neuroanatomy, neuropsychology, music psychology and humanistic psychology are
      primary sources in the development of models of clinical application (Hodges
      1996). Our main interests are focussed on the following issues and areas of
      clinical application: The initialisation of contact with patients in vegetative
      status Communicative interaction with patients who can not (initially) use verbal
      communication (aphasic disorders) Temporal motor organisation with patients with
      sensomotor disorders Cognitive organisation and mnemonic framework with patients
      with neuropsychological functional disorders (concentration, memory, perception)
      Treatment of spatial perception disorders (neglect) Enhancing personal and social
      integration following individual isolation, social withdrawal. These topics will
      be discussed and highlighted with clinical examples.

PMID- 11974985
TI  - The impact of treatment on survival roles of a person with a traumatic brain
      injury.
AB  - Over 250 survivors of brain injury were clinically evaluated and a long term care
      plan developed for each of them. 105 survivors were located and a follow-up
      questionnaire was administered at least two years later to the survivors and
      families to evaluate the predictions that were made regarding long-term needs.
      The study looked at the impact on eight survival roles as defined by WHO and
      attempted to determine the effectiveness of services, correlating various
      treatment modalities and services with changes, adjustments, accommodations,
      achievements, and future goals. Results showed that there is a correlation
      between some non-traditional therapies (Recreational and Cognitive) and for
      individuals' future goals in physical independence, mobility, community
      reintergration and self care. These future goals were not significant for
      occupational and physical therapies. Also, a less significant correlation was
      made between paid attendant care and level of outside activities.

PMID- 11974986
TI  - A computerized version of EBIS evaluation chart and its opportunities in the
      rehabilitation program of TBI patients.
AB  - The need of rehabilitation programs for severely traumatic brain injured (TBI)
      patients is great and is growing, but these programs are long, costly and it
      would be very useful if we could demonstrate and quantify the benefits of our
      approaches. We think that scarcity of literature in this field is a consequence
      of the well known and real difficulty in this kind of investigations (too many
      variability factors, groups of population not homogeneous, ethical problems for
      double blind studies and so on). It is our opinion that EBIS Protocol could be a
      very useful instrument for the evaluation of rehabilitation programs benefits,
      provided that the protocol is used regularly for a long time after the acute
      phase and in many different TBI centres: in this way it would be possible to
      compare and to elaborate data concerning a large number of patients. This
      instrument could also become an opportunity for a continuous and more coordinated
      collaboration between rehabilitation centres of different countries. We think
      that this target is realistic only if we dispose of a commonly accepted
      computerized version of EBIS Protocol with a data exchange via Internet. Since
      1996 we have been using a computerized version of the EBIS protocol for data
      archivation and follow up of TBI patients treated in our centre. The data bank
      concerns actually n. 341 TBI patients. Objective of the present research is the
      presentation of a computerized version of EBIS protocol. This program is freely
      available and it could contribute to a more common use of this evaluation tool.
      We thank particularly Prof. Truelle and Prof. Brooks who gave us the permission
      for the use of EBIS document.

PMID- 11974988
TI  - Clinical efficacy of stimulation programs aimed at reversing coma or vegetative
      state (VS) following traumatic brain injury.

PMID- 11974987
TI  - Satisfaction of life and late psycho-social outcome after severe brain injury: a
      nine-year follow-up study in Aquitaine.
AB  - In view of assessing their late outcome and satisfaction of life, 79 out of 158
      severe traumatic brain injury (STBI) patients who received inpatient
      rehabilitation in Aquitaine in 1993 were followed by phone interview. Results
      showed that 9 years on average after their injury, 65 to 85% of these patients
      were independent for daily living, whereas 35 to 55% only were independent in
      social life. Most of the patients were satisfied with their autonomy (67%),
      family life (66%) and financial status (41%), but they were dissatisfied with
      leisures (36%), vocational adjustment (28%) and sexual life (32%). Satisfaction
      of life was mostly related to age, gender, physical autonomy, need of help
      because of cognitive impairment and functional outcome as assessed by the Glasgow
      Outcome Scale. Severe traumatic brain injury (STBI) stands in industrialised
      countries as a major Public Health problem and a dreadful human drama for the
      patients, their families and the community [2]. A great number of STBI patients
      survive with severe disability, most of them being young adults. The most
      severely impaired may live only with their parents or in high-cost nursing homes.
      From a psychological point of view, STBI causes a total and sudden breakdown of
      the mental states, personality and conditions of life. Life plans and projects
      are definitively disrupted, satisfaction of life is deeply changed.
      Rehabilitation aims at improving functional outcome of persons with STBI, and at
      improving their overall quality of life. Planning for rehabilitation and re-entry
      into community of STBI patients need to be provided with precise data on their
      late outcome and disability level. Despite that the concepts of quality and
      satisfaction of life are difficult to define and moreover to assess, these are
      also major factors to take into account. The aims of the present study were to
      assess the late psycho-social outcome of patients hospitalized in Aquitaine for
      rehabilitation of a STBI 7 to 10 years after their injury, and to ask for their
      satisfaction of life and subjective feeling of quality of life.

PMID- 11974989
TI  - What is a good re-entry programme? What are the key-question?--J. Douglas Miller
      Memorial Lecture.

PMID- 11974990
TI  - Health management technology for catastrophic medical conditions.
AB  - BACKGROUND: The excessive growth of health care expenditures in the United States
      is widely acknowledged. Costs are anticipated to double by the year 2006. The
      intractable issue which remains before health care leaders is how to
      appropriately restrain these costs while not sacrificing a desired level of care
      quality. A variety of management approaches have been developed in pursuit of
      more rational and cost-effective use of health resources. Current management
      approaches have proven inadequate in stemming health care cost inflation and have
      raised increasing concerns about their negative impact on the quality of health
      care. METHOD: One group has created and operated a data and structured, expert
      consensus-driven health management technology for the management of catastrophic
      medical conditions, including severe brain and spinal cord injury and severe
      multiple trauma and burns, since 1992 and has recently applied this same
      technology to high risk neonates and organ transplants. This integrated, severity
      risk adjusted, delivery system incorporates adequate clinical data capture and
      analysis, coupled with empirically derived management principles and consensus
      expert clinical judgment. INTERPRETATION: Preliminary data analysis indicates
      that patients treated under the ParadigmHealth model experienced an improvement
      in the health care process, improved quality in health care delivery and
      outcomes, and overall cost reduction.

PMID- 11974991
TI  - The important role of pain in neurorehabilitation. The neurosurgeon's approach or
      (neurorehabilitation: the neurosurgeon's role with special emphasis on pain and
      spasticity).
AB  - Pain syndromes due to peripheral or central nervous system damage, or both, may
      hinder neurorehabilitation. Control of pain may be obtained by ablative or
      augmentative procedures. Of the ablative modes only DREZ and Cordectomy are still
      being employed in cases of pain due to Brachial Plexus Avulsion and conus and
      cauda damage at T9-L1: in both pain is not simply due to "deafferentiation". The
      augmentative procedures include spinal cord, deep brain and cortical stimulation.
      Subarachnoid infusion of drugs (midazolam, clonidine, baclofen, etc.) is a new
      avenue open to control pain. Indications, results and mechanisms of action of
      those procedures in neuropathic pain are discussed on the basis of literature and
      personal experience.

PMID- 11974992
TI  - Combined intrathecal baclofen and morphine infusion for the treatment of
      spasticity related pain and central deafferentiation pain.
AB  - OBJECTIVES: Complex pain syndromes due to spasticity and central deafferentation
      often fail to respond to medical therapy and create challenging problems in the
      pain management. So far, only spasticity associated musculosceletal pain has been
      reported to respond to intrathecal baclofen application [1, 2]. METHODS: We
      report the treatment of severe neuropathic pain in a patient with ED and the
      combined intrathecal application of baclofen and morphine in 5 patients with
      severe spasticity related pain. RESULTS: Continuous intrathecal baclofen infusion
      resulted in a pain free period of 20 months in the patient with ED. Patients with
      spasticity treated with intrathecal application of baclofen and morphine were
      pain free for a mean period of 2 years. CONCLUSION: Intrathecal baclofen and
      morphine application proved to be effective in spasticity related and central
      deafferentation pain and should therefore be considered in the management of
      these patients.

PMID- 11974993
TI  - The punctate midline myelotomy concept for visceral cancer pain control--case
      report and review of the literature.
AB  - INTRODUCTION: Nauta et al. first reported on a successful punctate midline
      myelotomy (PMM) at the spinal cord Th 10 level for the treatment of intractable
      pelvic cancer pain. CASE STUDY: The authors published another case history of a
      patient with multiple anaplastic carcinomas of the small intestine, peritoneal
      carcinosis and retroperitoneal lymphomas, suffering from severe visceral pain in
      the hypo-, meso-, and epigastrium. Nauta's PMM was successfully performed at the
      level Th 4. Narcotic medication was tapered from 30 mg i.v. morphine per hour
      preoperatively to 5 mg per hour within 5 days postoperatively. Pain intensity
      decreased from 10 to 2-3 on the visual analog scale. Only minor transient side
      effects appeared postoperatively. Pain reduction remained until the patient died
      from the extended disease five weeks later. DISCUSSION: Meanwhile Nauta et al.
      reported on 5 additional patients, in whom PMM led to a sufficient pain
      reduction. Another paper reported on sufficient control of visceral pain due to
      advanced stomach cancer after a modified Th 1-2 PMM. CONCLUSION: PMM sufficiently
      controls not only pelvic visceral pain, but also visceral pain generated in the
      meso- and epigastrium. The findings support the concept of a midline dorsal
      column visceral pain pathway.

PMID- 11974994
TI  - Deep brain stimulation therapy for a persistent vegetative state.
AB  - Twenty cases of a persistent vegetative state (PVS) caused by various kinds of
      brain damage were neurologically and electrophysiologically evaluated at 3 months
      after persistence of the PVS, and were treated by deep brain stimulation (DBS)
      therapy. The stimulation sites were the mesencephalic reticular formation (2
      cases) and CM-pf complex (18 cases). Seven of the patients emerged from the PVS,
      and became able to obey verbal commands. However, they remained in a bedridden
      state. These 7 cases revealed a desynchronization or slight desynchronization
      pattern on continuous EEG frequency analysis. The Vth wave of ABR and N20 of SEP
      could be recorded even with a prolonged latency, and the pain-related P250 was
      recorded with an amplitude of over 7 microV. We conclude that chronic DBS therapy
      may be useful for allowing the patient to emerge from a PVS, if the candidates
      are selected according to the neurophysiological criteria. In view of the
      severely disabled state of the patients who emerged from the PVS, a special
      rehabilitation program which includes neurostimulation therapy may be necessary
      for treatment of the PVS.

PMID- 11974995
TI  - Deep brain stimulation of the globus pallidus internus (GPI) for torsion dystonia
      -a report of two cases.
AB  - Generalized dystonia is known as a type of movement disorder in which
      pharmacotherapeutic options are very limited. Deep Brain Stimulation (DBS) is
      well established for Parkinson's disease (PD) and tremor dominant movement
      disorders. We report on two cases of generalized dystonia which were successfully
      treated by chronic high frequency stimulation in the Globus pallidus internus
      (GPI). Two 26 and 27 years old males suffered from severe torsion dystonia and
      multisegmental dystonia of the lower limbs. Case 1 is a familiar type of dystonia
      (DYT1 positive). The onset of symptoms in both cases was at age 7. The complaints
      were initially treated with orally administered benzodiazepines, anticholinergic
      drugs, later by baclofen and L-DOPA. However there was no response. Case 2 was a
      patient with a history of left side dominated dystonia since the age of 8. It was
      first diagnosed as a psychogenic movement disorder. Prior to surgery he was
      treated with L-DOPA, anticholinergics, Baclofen without any effect. There was
      only a limited effect on high doses of diazepam. The patient is DYT1 negative.
      The target point was on both sides the GPI. Intraoperative computerized
      tomography (CT) and ventriculography (VG) were used for target setting.
      Furthermore microrecordings were helpful to ensure the exact electrode position.
      Surgery was performed under analgosedation. Two weeks after surgery we first
      observed a relief of symptoms in both cases. A significant reduction in the Burke
      Fahn-Marsden-Dystonia Movement Rating Scale was observed at the 6 month follow-up
      (case 1: 95%, case 2: 80%). In case 1 a slight dystonic movement of the left
      ankle was the only remaining symptom under stimulation. The medication was
      continuously reduced. At the 24 month follow-up the effect of stimulation
      remained unchanged. However high stimulation parameters are required to maintain
      an optimal effect (mean 3.5 V, 400 microseconds, 145 Hz).

PMID- 11974996
TI  - Control of post-stroke movement disorders using chronic motor cortex stimulation.
AB  - The effects of motor cortex (MC) stimulation on post-stroke movement disorders
      were analyzed in 50 patients. These individuals either underwent MC stimulation
      primarily for the purpose of controlling their post-stroke involuntary movements
      (n = 8) or underwent MC stimulation for the purpose of controlling their post
      stroke central pain (n = 42). In the latter patients, the effects of MC
      stimulation on co-existent involuntary or voluntary movement disorders were
      analyzed retrospectively. Good control of involuntary movements was observed in 2
      of 3 patients with hemichoreo-athetosis, 2 of 2 patients with distal resting or
      action tremor, and 1 of 3 patients with proximal postural tremor. Subjective
      improvements in motor performance were reported by 8 patients who had mild motor
      weakness, and the effects appeared to be attributable to attenuation of rigidity.
      We consider that these findings justify further clinical studies on MC
      stimulation for the control of post-stroke movement disorders.

PMID- 11974997
TI  - Vagus nerve stimulation for epilepsy, clinical efficacy of programmed and magnet
      stimulation.
AB  - RATIONALE: Vagus nerve stimulation (VNS) by intermittent and programmed
      electrical stimulation of the left vagus nerve in the neck, has become widely
      available. It is an effective treatment for patients with refractory epilepsy.
      Patients can be provided with a magnet that allows to deliver additional
      stimulation trains. Since earlier studies have demonstrated the persistence of a
      stimulation effect after discontinuation of the stimulation train, we evaluated
      the clinical efficacy of VNS both in the programmed intermittent stimulation mode
      and magnet stimulation mode. METHODS: A group of 30 patients (16 F, 14 M) with
      medically refractory partial epilepsy, who were unsuitable candidates for
      resective surgery, were included in the study. The patients, their companions and
      caregivers were instructed on how to administer additional stimulation trains
      using a hand-held magnet when an aura or a seizure onset occurred. Patients or
      caregivers could recognize habitual seizures and were able to evaluate sudden
      interruption of these seizures. Using seizure diaries, detailed accounts of
      magnet use and regular clinic follow-up visits, data on seizure frequency and
      severity and number of magnet applications were collected. Patients who provided
      unreliable information were excluded from the analysis. RESULTS: Forty-seven
      percent of all patients had an improvement in seizure control with a reduction in
      seizure frequency of more than 50% during a mean follow-up of 33 months (range: 4
      67 months). More than half of the patients used the magnet and provided reliable
      information. In 63% of patients who were able to self-administer or receive
      additional magnet stimulation, seizures could be interrupted, be it consistently
      or occasionally. More than half of the patients who reported a positive effect of
      magnet stimulation became responders. In most cases the magnet was applied by a
      caregiver. CONCLUSIONS: To our knowledge, this study is the first to explore the
      efficacy of magnet-induced vagus nerve stimulation. Results suggest that the
      magnet is a useful tool that provides patients and mainly caregivers with an
      additional means of controlling refractory seizures. Additional controlled
      studies comparing programmed stimulation and magnet-induced stimulation in
      monitoring conditions are warranted.

PMID- 11974998
TI  - Computer added locomotion by implanted electrical stimulation in paraplegic
      patients (SUAW).
AB  - Paraplegia means a live long sentence of sensory loss, paralysis and dependence
      with approximately 1000 new victims in every European country every year and
      11.500 new traumatic SCI cases in the US. respectively. Sixty percent are injured
      before age 30. More than 90% of SCI victims may survive with nearly normal
      experience of live. Most patients will recover somewhat from SCI over time but no
      patient who remained plegic for one year regains voluntary motor function after
      that time period. Despite remarkable efforts and recent achievements in
      rehabilitation no treatment can be recommended so far to enhance functional
      recovery and restoring locomotion in paraplegic humans. FES as a technical
      compensation has become therefore a challenging treatment to restore muscle
      function and to prevent atrophy and to improve mobility and quality of life at
      the same time. In paraplegics FES could be the basis to restore locomotion. One
      of the advantages of an implanted FES version (neuroprosthesis) is that the FES
      system, electrodes, and cables remain permanently implanted within the body, so
      that the patient can stay without cables, the programmer attached to the
      crutches. The SUAW project, supported under BIOMED II Programme by the European
      Community was aimed to finalize and to put into practice the results of previous
      research and development. The novel implant with an ASCI-Chip has 16 channels, 8
      on each side, 20 mA for monopolar and 2 mA for bipolar stimulation, only one
      electrode can be stimulated at a given time. Stimulation of 6 muscle groups of
      both legs are known to be sufficient for locomotion: M. ileopsoas (erector of the
      body, hip flexor), M. gluteus maximus (hip extensor), M. gluteus medius (lateral
      hip stabilisator, knee abductor), Mm. hamstrings (knee flexor) stimulated by
      epimysial electrodes, Mm. sartorius and rectus femoris (knee extensor) stimulated
      by neural, bipolar electrodes. Patient's selection criteria were: stable spinal
      cord lesion between T7 and T11, minimum 1 year after the accident without
      deformity of the spine, the muscle groups for locomotion responding to external
      FES with the EXOSTIM programmer with the same programme used later for the
      neuroprosthesis. Two paraplegic male patients, T8, 38 and 31 years old
      respectively, were operated on by an international group of surgeons according to
      the protocol in 09/1999, respectively 7/2000. The postop. course was uneventful.
      Because the threshold of the primary implant was too low regarding scare tissue
      around the electrodes, this implant was changed in 01/2000 and worked perfectly.
      Both patients are happy with the success of the novel treatment modalities.

PMID- 11974999
TI  - Why suicide bombing...is now all the rage.

PMID- 11975000
TI  - Making time for a baby.

PMID- 11975001
TI  - The cost of starting families first. For those who choose to have children early
      in life, the trade-off may involve more than just money.

PMID- 11975002
TI  - Cousins: a new theory of relativity.

PMID- 11975003
TI  - Licking the habit.

PMID- 11975004
TI  - Is there a doctor onboard?

PMID- 11975005
TI  - What the nuns didn't know. Could they have uncovered abuse? Not in a culture that
      kept them in the dark.

PMID- 11975006
TI  - Single moms unite.

PMID- 11975008
TI  - Staying on the road.

PMID- 11975007
TI  - Rainbow network.

PMID- 11975009
TI  - Fixing the rift.

PMID- 11975010
TI  - [The long-term follow up after trabeculectomy].
AB  - THE AIM OF THE STUDY: To estimate the efficacy of trabeculectomy for primary open
      angle glaucoma. MATERIAL AND METHODS: Since 1990 to 2000 we observed 91 eyes of
      79 patients (53 women and 26 men) aged 39-86. The results of performed surgery
      were valued directly after the trabeculectomy and in period of over 8 years. We
      carried out the examinations of visual acuity, intraocular pressure, visual
      field, state of optic nerve head, type of bleb following trabeculectomy and the
      necessity of applying additional topical treatment. The trabeculectomies were
      performed in a typical way. Some surgeons made a square or triangular superficial
      scleral flap based at the limbus, measuring from 2.5 x 3.0 to 4 x 4 mm or 3 x 3
      mm. The deep block of scleral tissue with trabeculum (from 0.5 x 1.0 to 2.5 x 3.0
      mm) was excised, the superficial cauterisation and the peripheral iridectomy were
      performed in every case. The scleral flap and conjunctiva were sutured with 10/0
      Ethilon, 8/0 Vicryl or 6/0 Mersilk. RESULTS: The patients were divided into 3
      groups depending on observation period: I--up to 4 years, II--from 5 to 8 years,
      III--over 8 years. We confirmed the normalisation of IOP in 80%, 73%, 90% and the
      successful control of visual field (no progress) in 82%, 77%, 70% of adequate
      groups. In the first and second group 45-50% of patients could resist from
      topical treatment, but after 8 years as many as 80% required additional
      pharmacological treatment. CONCLUSION: The trabeculectomy is the effective
      surgery in most patients with open angle glaucoma. The effectiveness of
      trabeculectomy can be controlled by the size of extracted deep scleral flap with
      trabeculum. For the stability of visual field it is necessary to keep the
      intraocular pressure at 13-18 mm Hg level.

PMID- 11975011
TI  - [Eyelid reconstruction after removal of tumours, using chondroperichondrial
      grafts from auricular concha].
AB  - INTRODUCTION: The main goal in reconstruction of the full thickness defects of
      the eyelids after tumour resection is the reconstitution of the tarsal plate as
      supportive layer of the lid. AIM OF STUDY: We report a simple, one stage
      reconstruction procedure of repairing the eyelid internal lamella. METHOD: The
      chondroperichondrial graft from auricular concha was used to reconstruct the
      tarsoconjunctival layer in nine patients with surgical defects following excision
      of skin cancer. Local cutaneous flaps were used to reconstruct the external
      lamella. RESULTS: All grafts appeared completely without reabsorption, healing of
      the wounds was rapid. Epithelialization on the perichondrium from the surrounding
      conjunctiva occurred between 2 and 3 weeks. The functional and aesthetic results
      were judged as very good in seven patients after reconstruction of the lower
      eyelid. One patient after reconstruction of the upper eyelid has good result too.
      The last patient needed secondary very extensive operation because of the tumour
      recurrence. CONCLUSIONS: Conchal chondroperichondrial free graft provides simple,
      one-stage reconstruction of the lower and upper eyelid. Perichondrium substitutes
      the conjunctiva in early postoperative period and it makes epithelialization
      possible.

PMID- 11975013
TI  - [The influence of the hormonal replacement therapy on the amount and stability of
      the tear film among peri- and postmenopausal women].
AB  - PURPOSE: To estimate the amount of the tear-film and its stability among women
      treated due to endocrinological or gynecological indications with hormone
      replacement therapy. MATERIAL AND METHODS: 60 women treated with hormonal
      replacement therapy (HRT) were divided into 3 groups of examination: group 1 (20
      women), treated with HRT after up to 1 year of menopausal symptoms, group 2 (20
      women) treated with HRT between 1-5 years of menopausal symptoms, group 3 (20
      women) treated with HRT after more than 5 years of menopausal symptoms. The
      secretion of the tear-film was measured using Schirmer I test and lisozyme test.
      The stability of the tear-film was measured with respect to the break-up time
      (BUT). The examinations were performed 3, 6, 12 months after HRT treatment. The
      values obtained before HRT treatment served as control. RESULTS: Before HRT
      treatment we observed significantly decreased tear secretion and lower stability
      in group 2 and group 3 as compared with group 1. We noticed the negative
      correlation between the secretion of the tear film as compared to age of examined
      women. HRT made the tear secretion significantly increased in group 2 and group 3
      after 6, 12 and 3, 6, 12 months of HRT treatment respectively. We assessed a
      significant improvement of the tear film stability with respect to BUT in group 2
      and 3 in all months of HRT treatment. We found significant correlation between
      modified Schirmer I test and lisozyme test (p < 0.001). CONCLUSION: The age and
      changes of the hormonal homeostasis have negative influence on the tear
      secretion, tear-film stability among peri and postmenopausal women. HRT treatment
      has beneficial influence on the tear film secretion and tear stabilization. Our
      results suggest that hormonal replacement therapy can be suitable for the
      treatment of the postmenopausal dry eye syndrome.

PMID- 11975012
TI  - [The vision organ evaluation in children with heparin modified intraocular lens
      implants].
AB  - PURPOSE: The aim of the work was to estimate the vision organ state in children
      with IOLs-PMMA and heparin modified IOLs operated on different types of cataract.
      MATERIAL AND METHODS: Material comprised 65 eyes with congenital, traumatic and
      complicated cataract in patients aged from 3 months to 17 years. Visual acuity
      and anatomic state of eyes with IOLs were evaluated. CONCLUSIONS: Results
      indicate the suitability of heparin modified IOLs implantation in children with
      different types of cataract.

PMID- 11975015
TI  - [Selected parameters of cellular immunity in uveitis in children].
AB  - Evaluation of lymphocyte in children with uveitis basing on the study of T
      lymphocyte subpopulation in the peripheral blood using the flow cytometry method
      is presented. Cytometric analysis of peripheral blood lymphocytes using
      fluorochrome-marked monoclonal antibodies was carried out in 29 children, aged 6
      18, with parasitic uveitis (group A) and with uveitis of another aetiology (group
      B). Control group consisted of 28 healthy children aged 6-15. The absolute values
      of T lymphocytes were higher in groups A (x = 1.60 +/- 0.53) and B (x = 1.81 +/-
      0.40) compared to controls (x = 1.50 +/- 0.38). The lowest percentage of CD4+
      lymphocytes (x = 34.25 +/- 6.06) and the highest percentage of CD8+ lymphocytes
      (x = 31.14 +/- 6.50) were revealed in children with parasitic uveitis. The lowest
      index CD4+/CD8+ (x = 1.29 +/- 0.53) in the group of children with parasitic
      uveitis reflects severe disorders in response regulation. However, the percentage
      values of NK cells were lower in the two groups of patients compared to controls.
      The results allow for the assumption that quantitative changes in the
      subpopulation of peripheral blood lymphocytes are more pronounced in parasitic
      uveitis.

PMID- 11975014
TI  - [The influence of the hormonal replacement therapy on conjunctival epithelium
      morphology among peri- and postmenopausal women].
AB  - PURPOSE: To estimate the status of the conjunctival morphology among women
      treated due to endocrinological or gynecological indications with hormone
      replacement therapy. MATERIAL AND METHODS: 60 women treated with hormonal
      replacement therapy (HRT) were divided into three groups of examination: group 1
      (20 women), treated with HRT after up to 1 year of menopausal symptoms, group 2
      (20 women) treated with HRT between 1-5 years of menopausal symptoms, group 3 (20
      women) treated with HRT after more than 5 years of menopausal symptoms. The
      morphology of the conjunctival epithelium was assessed by impressive cytology.
      The examinations were performed 3, 6, 12 months after HRT treatment. The values
      obtained before HRT treatment served as control. RESULTS: The preliminary
      examinations showed changes of the morphology of conjunctival epithelium in all
      groups. The longer duration of postmenopausal period, the more advanced
      morphological changes. In all groups of examinations the HRT has the beneficial
      influence on the state of conjunctival epithelium morphology. CONCLUSION: The age
      and changes of the hormonal homeostasis have negative influence on conjunctival
      epithelium morphology among peri- and postmenopausal women. HRT treatment has
      beneficial effect on the conjunctival epithelium morphology. Our results suggest
      that hormonal replacement therapy can be suitable for prevention and treatment of
      postmenopausal conjunctival changes.

PMID- 11975016
TI  - [Selected markers of T cell activation in children with idiopathic uveitis].
AB  - The aim of our investigation was to assess T cell activation markers (CD69, HLA
      DR, CD25, CD49a) in idiopathic uveitis. T cells from children aged 9-17 with
      idiopathic uveitis were studied. Monoclonal antibodies against chosen markers of
      T cell activation were used. Expression of the CD69, HLA-DR, CD25, CD49a were
      determined by flow-cytometry. HLA-DR and CD49a--marker of the late activation-
      were significantly increased.

PMID- 11975017
TI  - [Research of myopia development in children with self-regression of retinopathy
      of prematurity and in children with regression after cryotherapy].
AB  - PURPOSE: The aim of the paper is to estimate the influence of self-regression of
      retinopathy of prematurity (ROP) and regression after cryotherapy for development
      of axial myopia in premature babies. MATERIAL AND METHODS: The researches
      concerned 4 groups of premature babies in the 6th, 12th and 24th month of life.
      Group 1--without ROP, group 2--with self-regression of ROP, group 3--with
      regression of ROP after cryotherapy and group 4--with one eye with self
      regression of ROP and second eye with regression after cryotherapy. RESULTS: In
      the 6th and 24th month of life mean axial length of eyeball in children from
      group 3 was statistically significantly higher than mean axial length of eyeball
      in children from group 1 and 2. In the 12th month of life mean axial length of
      eyeball in children from group 3 was statistically significantly higher than mean
      axial length of eyeball in children from group 1. In group 4 mean axial length of
      eyeball with regression of ROP after cryotherapy was statistically significantly
      higher than mean axial length of eyeball with self-regression of ROP.
      CONCLUSIONS: Self-regression of ROP and regression of ROP after cryotherapy may
      cause development of axial myopia in premature babies.

PMID- 11975018
TI  - [Retrospective evaluation of PC IOL power after extracapsular cataract
      extraction].
AB  - PURPOSE: Retrospective evaluation of PC IOL power calculation accuracy and
      comparison of the refractive errors after ECCE resulted from different methods of
      calculation. MATERIAL AND METHODS: The PC IOL power in 100 eyes with senile
      cataract without significant refractive errors, was calculated using SRK II
      formula with two different biometers and based on primary refraction. The final
      IOL power was established by surgeon based on all mentioned calculations (surgeon
      choice). Half a year after surgery the refractive error was measured. The proper
      IOL power, which did not require additional correction, was calculated (ideal
      lens). RESULTS: 48 eyes did not require any distance correction. In 44 eyes small
      hyperopia (to +2.0 D) appeared and in 8 eyes myopia (to -1.5 D). The smallest
      error was made in cases where we implanted lenses according to surgeon choice.
      The average power of ideal lens was 20.32 D. We observed statistically
      significant difference between both ultrasound biometers. CONCLUSIONS: The most
      accurate results were achieved in cases where IOL power was chosen by the surgeon
      based on SRK II formula and primary refraction. Possible source of errors can be
      inadequate indications of biometers.

PMID- 11975019
TI  - [Pharmacodynamics and pharmacokinetics of prostaglandins and their derivates in
      eye tissues].
AB  - This paper presents the classification of prostaglandins and their receptors. The
      ocular distribution of the receptors and the effects of their agonists are
      presented. The efficacy in lowering intraocular pressure of different
      prostaglandins and their derivatives, especially the PGF2a group, is discussed.
      The history of latanoprost development is also presented. Good therapeutic index
      characterises two antiglaucomatous PG-derivatives: latanoprost and unoprostone.

PMID- 11975020
TI  - [Ophthalmic complications in the course of opportunistic infections--part I].
AB  - One of the most important problem of contemporary medicine appears to be
      constantly increasing number of patients with opportunistic infections. The
      situation is mainly due to world epidemic of AIDS. The progress in
      transplantology, huge number of immunocompromised patients during oncological and
      hematological treatment as well as prolongation of life time in children with
      congenital immunodeficiencies are successive conditions for the development of
      opportunistic infection. Pathogens infecting immunocompromised individuals have
      very low virulence, but in these persons disease is often very severe and
      potentially lethal. Main agents responsible for opportunistic infections are:
      Toxoplasma gondii, Cytomegalovirus hominis, Herpes simplex virus, Varicella
      zoster virus and fungi. In the paper we describe clinical symptoms, diagnostic
      methods and therapies of ocular toxoplasmosis and viral infections. Knowledge of
      diagnosing methods and treatment of opportunistic infections which, when
      untreated, may quickly lead to vision loss, is necessary in contemporary
      ophthalmological practice.

PMID- 11975021
TI  - [Current state of knowledge on the subject of astigmatism etiopathogenesis].
AB  - PURPOSE: To present current state of knowledge on the subject of astigmatism
      etiopathogenesis. MATERIAL AND METHODS: A review of contemporary literature
      concerning pathomechanism of astigmatism. RESULTS: The optical, morphological and
      functional changes taking place in the visual pathway during the astigmatism are
      described. Special attention was focused on the functional modifications in the
      neuronal system of Brodmann's 17th area. The frequency of occurrence as well as
      the forms of astigmatism among children and adults are characterized. The results
      of papers indicating environmental and genetic reasons of astigmatism as well as
      the possible pathomechanism of astigmatism creation are presented. The necessity
      of astigmatism treatment before the end of visual cortex plasticity has been
      pointed out. The attitude towards some surgical methods of astigmatism treatment
      is expressed.

PMID- 11975022
TI  - [Management in preretinal macular hemorrhage. Case report].
AB  - The report presents a method of management in case of clotted premacular
      haemorrhage in a 46 year-old woman. The used method of treatment proceeded in 2
      stages: 1) pars plana, intravitreal injection of 50 mg tissue plasminogen
      activator (tPA-Actilise), 2) after 24 hours intravitreal 0.5 cc SF6 with air
      mixture (1:5). Fibrinolytic tPA action and mechanic action of expanding gas
      caused after argon laser puncture intravitreal haemorrhage dislocation and
      following its resorption. The almost full visual acuity persisted for over 2
      years.

PMID- 11975023
TI  - [Pars plana vitrectomy in treatment of ocular toxocariasis complications--case
      report].
AB  - Ocular toxocariasis in adults may cause serious diagnostic and therapeutic
      problems. We describe a case of a 54-year-old farmer who developed peripheral
      granuloma with dense connective tissue strands joined to the disc. The diagnosis
      was confirmed by high ELISA titers in the serum and vitreous body. We performed
      pars plana vitrectomy with epiretinal membrane removal and laser photocoagulation
      of the inferior retina, obtaining improvement of visual acuity. After a few weeks
      the patient returned with central retinal detachment and macular hole. After the
      second vitrectomy with use of silicon oil we obtained reattachment of the retina
      but without functional improvement.

PMID- 11975024
TI  - [Treatment of eyelid hemangioma in children with intralesional steroid
      injection].
AB  - Infantile hemangiomas affect about 5% (3-10%) of the population, showing a
      predilection for the face. Infants with hemangiomas of the eyelid are at risk
      amblyopia and strabismus. This is also a cosmetic defect. Several methods of
      treating these tumors have been associated with many complications. The use of
      intralesional steroid injections seems to be a simple, safe and effective method
      of treating hemangiomas of the eyelid in children.

PMID- 11975025
TI  - [Importance of echocardiography in prognosis of surgical outcomes in
      cholecystitis in elderly patients].
AB  - The authors propose to use more often echocardiography (EchoCG) in examination of
      elderly (over 60 years) of age patients with cholecystitis that permits to
      increase surgical activity to 92.4%. Left ventricular ejection fraction is the
      most informative. When this fraction is lower than 45% surgery must be
      recommended on vital indications only. EchoCG was used in 155 patients with
      cholecystitis, 131 of them were operated. 2 (1.52%) patients died due to acute
      cardio-vascular insufficiency and pulmonary artery thromboembolism.

PMID- 11975026
TI  - [Roentgeno-endovascular occlusion and surgical correction of patent ductus
      arteriosus].
AB  - To establish the indications to classical surgical correction and
      roentgenoendovascular occlusion (REO) of patent ductus arteriosus (PDA) results
      of treatment of patients with PDA were compared. Immediate results of treatment
      of 209 patients with PDA were analyzed. 110 patients underwent classical surgical
      operations which were performed successfully in 109 (99%) patients. Complications
      in early postoperative period were the following: incomplete expanding of the
      left lung in 1 (0.9%) patient, reactive exudation into left pleural cavity--in 1
      (0.9%), and chylothorax--in 1 (0.9%). REO of PDA was performed in 99 patients.
      Gianturco coils (COOK, Denmark) and Saveliev--Prokubovsky occluders were used.
      REO was successful in 93 (93.9%) patients. It failed in 6 (6%) cases including 3
      cases with coils and 3--with Saveliev--Prokubovsky occluders. According to the
      results, PDA with diameter less than 4 mm in the narrowest part can be closed by
      REO with Gianturco coils. In PDA with diameter 4-10 mm Saveliev--Prokubovsky
      occluders are recommended. In case of PDA with diameter more than 10 mm,
      aortopulmonary defect or septic botallitis it is necessary to perform thoracotomy
      and surgical correction.

PMID- 11975028
TI  - [Treatment of tracheal cicatricial stenosis].
AB  - Cicatricial stenosis and tumors are the main indications for tracheal surgery.
      From 1963 to January 2001 323 patients were operated for cicatricial stenosis of
      trachea. In 287 (88.9%) patients tracheal stenosis was iatrogenic after
      respiratory reanimation. In 191 (59.1%) patients tracheal stenosis located in
      cervical part of the trachea. In 67 of them it combined with stenosis of
      subplicalis part of the larynx. Lesion of cervical-upperthoracic trachea was seen
      in 57 (17.6%) patients, thoracic part--in 69 (21.4%). Total lesion of trachea was
      diagnosed in 6 (1.9%) patients, in 2 of them tracheal bifurcation and both main
      bronchi were involved in cicatricial process. Indications for surgery were in 238
      (73.7%) patients. 85 (26.3%) patients underwent endoscopic treatment. The main
      operations were circular resection and staged reconstructive-plastic surgeries.
      303 patients were discharged, 20 patients died, hospital lethality was 6.6%.
      Intra- and postoperative complications were seen in 93 (13.4%) cases. Good and
      satisfactory long-term results were achieved in 85.1% patients. Unsatisfactory
      long-term results were associated with postoperative complications.

PMID- 11975027
TI  - [External respiration function in patients with exudative pleurisy before and
      after video-thoracoscopic operations].
AB  - 57 patients with exudative pleurisy were observed. Function of external
      respiration was examined with traditional spirometry and a new method--distant
      spirometry. Function of cardio-vascular system was examined with
      electrocardiography and echocardiography. The new method of monitoring permits to
      perform repeated and daily examinations of external respiration function. The
      method is highly informative, sabe, physiological, permits to evaluate general
      and isolated ventilation of the lungs simultaneously, and demonstrates dynamics
      of exudate accumulation that may help in choice of treatment policy.

PMID- 11975029
TI  - [Stomach resection from mini-approach in complicated ulcers of duodenal posterior
      wall].
AB  - 6 cases of Bilrot-I stomach resection from mini-approach for ulcers of duodenal
      posterior wall complicated by pyloric stenosis and penetration into pancreatic
      head are described. Precise technique was used. Orientation of the incision to
      pancreatic head and suprapyloric gastrotomy create good conditions for
      orientation, precise dissection of the affected part of the duodenum and creation
      of one-layer gastroduodenoanastomosis. Tunnelization of retrobulbar fat tissue
      and alternating traction up by dissected stomach made surgery easier. The
      operated patients were followed up from 1 months to 2 years: function of
      anastomosis was satisfactory.

PMID- 11975030
TI  - [Importance of some apudocytes in gastric ulcer bleeding prediction].
AB  - In 6 patients with uncomplicated gastric ulcer (GU) and 8 patients with GU
      complicated by acute bleeding morphohistochemical and ultrastructural analysis of
      apudocytes of gastric mucous membrane in the ulcer, periulcer and remote zone was
      carried out with detection of morphofunctional changes predicting ulcer bleeding.
      It is established that G- and ECL-apudocytes hyperplasia and hyperfunction in
      these zones have stable, irreversible nature in gastric ulcer bleeding, and are
      reliable prognostic criteria of this complication.

PMID- 11975032
TI  - [Surgical stress in different cholecystectomies].
AB  - For determination of surgical stress degree and evaluation of long-term results
      prospective randomized study was carried out. Three representative groups were
      compared: patients undergone traditional cholecystectomy (TCE)--95 patients (1
      group), laparoscopic cholecystectomy--91 patients (2 group), minimally invasive
      cholecystectomy--92 patients (3 group). Level of stress hormones (before, during
      and after surgery), parameters of external respiration (before and after
      surgery), doses of analgetics (or their combinations) which were necessary for
      adequate analgesia in early postoperative period depending on surgical method
      were used as objective criteria of surgical stress. Based on evaluation of
      patients quality life reliable difference in first three years after surgery
      between patients undergone TCE and ones undergone minimally-invasive surgery was
      demonstrated.

PMID- 11975031
TI  - [Endogenic intoxication in patients with acute general peritonitis and problems
      of its correction].
AB  - This study was carried out for improvement of extracorporeal detoxication
      results. Distribution of middle-mass molecules (MM) in various media and vascular
      beds in patients with acute general peritonitis (AGP) and correlation between
      central hemodynamics (CH) and level of MM-intoxication were studied. Results of
      treatment were analyzed in 72 patients with AGP. Ultraviolet irradiation of
      autoblood (UVIA) had negative influence on circulation in patients with AGP in
      terminal stage who had more severe primary disorders of CH. Therefore, UVIA
      without hemosorption (HS) in these patients is potentially dangerous because of
      undesirable hemodynamic effects due to increase of MM-concentration in blood
      plasma. HS was performed 1.5-2 hours after UVIA and resulted in decrease of MM
      concentration in caval system blood by 28.1% with subsequent slow increase, MM
      level restored 24 hours after HS. If HS and UVIA were carried out simultaneously,
      MM-concentration in caval system blood decreased by 13.9% only, an in 3 of 7
      cases MM-concentration didn't change. Combination of UVIA and HS with 1.5-2 h
      interval is most effective.

PMID- 11975033
TI  - [Bioelectric myocardial activity in orthopedic surgery with autohemotransfusion].
AB  - 20 patients who have undergone difficult operations on locomotor apparatus with
      autohemotransfusion were examined. Twenty-four-hour ECG-monitoring before and
      after operation was used for registration of bioelectric myocardial activity.
      Tachycardia, in night time chiefly, disorders of circadian cardiac rhythm,
      ischemic depression of ST-segment without clinical symptoms were revealed in all
      the patients in postoperative period. These disorders are maximal in older age
      group that must be taken into account during planning surgery and
      hemotransfusion.

PMID- 11975034
TI  - [Volvulus of the pancreas in a pregnant woman with translocation of abdominal
      organs into the left pleural cavity].

PMID- 11975035
TI  - [Treatment of multiple cholangiogenous hepatic abscesses].

PMID- 11975036
TI  - [Actual problems of donation in liver transplantation. Part 2].

PMID- 11975037
TI  - [Diagnosis and treatment of exudative pleurisy].

PMID- 11975038
TI  - [Purulent cholangitis].

PMID- 11975039
TI  - [F. I. Inozemtsev (For the 200-th anniversary of his birthday)].

PMID- 11975040
TI  - [The calendar of anniversaries from the history of surgery in 2002].

PMID- 11975041
TI  - [Etiology, pathogenesis and clinical course of unstable coronary artery disease].
AB  - The clinical presentations of ischemic heart disease comprises the term of acute
      ischaemia syndromes, that include unstable angina pectoris, non-Q-wave myocardial
      infarction, Q-wave-myocardial infarction and sudden death. Among the different
      presentations of acute ischemic syndromes, tha unstable angina and non-Q-wave
      myocardial infarction can be regarded together. In both pathologic entity, the
      plaque rupture, or erosion signifies the primary event, which is the source of
      the highly thrombogenic substances coming out from the core of the
      atherosclerotic plaque and entering to the coronary and systemic circulation.
      They cause a thrombocyte-rich "white" intracoronary thrombus, that is not fully
      obstructive, or there is adequate collateral circulation, being the pathogenetic
      substrate that prevents the development of transmural necrosis. The nosologically
      bound two clinical entity can be called as "unstable coronary artery disease"
      (UCAD), since they have uniform etiologic, risk stratification and therapeutic
      backgrounds and also therapeutic targets that are basically distinct, they are
      admitted for transmural "ST-elevation" infarction. The review is discussing the
      etiology, pathophysiology, the role of inflammation factors, the problems of
      diagnostics, as well as risk stratification of the disease in the light of the
      recent guidelines of the European Society of Cardiology and multicenter evidence
      based studies.

PMID- 11975042
TI  - [Hodgkin lymphomas: current understanding of pathogenesis and pathomorphology].
AB  - Brief summary of the history of Hodgkin disease as well as presentation of the
      current REAL/WHO classification of the Hodgkin lymphoma actually including two
      diseases entities is given. Beside the morphological, phenotypical and
      clinicopathological characterization of the classical as well as the nodular
      lymphocyte predominant Hodgkin lymphoma emphasis is placed on the differential
      diagnostics of the two basic types of Hodgkin lymphomas as well as on that of
      nodular paragranuloma versus nodular lymphocyte rich classical Hodgkin lymphoma.
      Summarizing the last decade's progress in research the current understanding of
      the pathogenesis of Hodgkin lymphomas is presented. The key elements of it is
      that although the tumor cells of both Hodgkin lymphomas arise from B-cells having
      passed the germinal center phase and exhibiting somatic hypermutation, the tumor
      cells of classical Hodgkin lymphoma do not have a functional immunoglobulin gene,
      but show a thorough phenotypic change, whereas the tumor cells of nodular
      paragranuloma preserve the B-phenotype and being under antigen selection
      pressure. The role of Epstein-Barr virus in the etiology is also introduced.

PMID- 11975043
TI  - [Malignant arrhythmias caused by hyperkalemia: a new area of drug-induced
      electrolyte abnormalities].
AB  - INTRODUCTION: High dose of angiotensin converting enzyme inhibitor is indicated
      in the treatment of heart failure and it is part of the treatment in the patients
      suffering from diabetes mellitus and nephropathy. The patients with preexisting
      renal insufficiency could have slowly elevated serum potassium level treated by
      angiotensin converting enzyme inhibitor. PATIENTS: Seven acute admitted cases is
      presented with severe hyperkalaemia and life threatening arrhythmias caused by
      ACEI administration. Wide QRS accelerated rhythm was detected in two cases and
      bradyarrhythmias in five cases. Two patients died among the bradyarrhythmias.
      CONCLUSIONS: The authors call the attention of danger of high dose angiotensin
      converting enzyme inhibitor in patients with preexisting renal insufficiency and
      concomittant drugs elevating serum potassium level.

PMID- 11975044
TI  - [Dead-channel-like part of thoracic esophagus: cut-off sign in the upper
      gastrointestinal tract].
AB  - The colon cutoff sign had been published four decades ago. AIM OF THE STUDY: In
      this retrospective study a new localisation of syndrome seen on plain film
      esophagography. PATIENTS: The syndrome is formal in 32 cases (2.23%) of 1430
      patients is described. Touched persons are 76 +/- 9 years old. RESULTS: The
      arched inflexion of supradiaphragmatic esophagus related to stage of osteoporosis
      and incidence of vertebral body fractures besides height of thoracic cavity and
      kyphosis. Its convexity to abnormality of phrenicoesophageal membrane and hiatus
      is attributed. The deformity of esophagus occurs 3.75 seven times more often in
      female than in male patients. CONCLUSION: Not provable esophageal autopathies.

PMID- 11975045
TI  - [Biomechanical experiments for measuring traction lengthening of the lumbar spine
      during weight bath therapy].
AB  - INTRODUCTION: Weight-bath as an effective traction therapy has successfully been
      applied in Hungary for nearly a half century, however, it has still been
      constrained exclusively to empirical bases until the numerical biomechanical
      analysis of Bene and Kurutz appeared in 1993. Due to their calculations, for
      cervical suspension in traction bath, the value and distribution of tensile force
      along the spine became known, however, the most important information, namely,
      the deformation of spine segments to be stretched by the therapy is so far
      unknown. AIMS: In this paper the results of a wide-ranging in vivo biomechanical
      experimental analysis are presented, aimed partly to obtain the traction
      deformation effects of weight-bath therapy, partly to obtain the biomechanical
      traction model of human lumbar segments. The analysis aimed to clear the effect
      of decompression, extra weights, sex, aging, body height and weight.
      PATIENTS/METHODS: The experiments have been executed during the prescribed 20
      minutes long weight-bath treatment of patients having indication for cervical
      suspension. Patients with other forms of suspension, like armpit bars, have been
      excluded from the analysis. Two groups of patients have been distinguished: 67
      patients without and 88 patients with extra weight loads of 20-20 N (2-2 kgf)
      applied on the ankles. Extension values of lumbar segments LIII-IV, LIV-V and LV
      SI have been measured. Tensile deformations have been specified as the change of
      the distance between two spinous process of vertebrae, measured by a special
      subequal ultrasound method developed by the research group. The experimental
      results have been evaluated by using special software for analyzing ultrasound
      pictures. More than 3500 ultrasound pictures of 400 lumbar segments of 155
      patients have been measured and evaluated. RESULTS: As for the results, at the
      end of the treatment, elongation of lumbar segments has been demonstrated
      practically in 60% of patients without and in 75% of patients with extra weights.
      The mean extension of a lower lumbar segment after a 20 minutes long weight-bath
      treatment is about 1.2-1.4 mm, while with extra weights it is about 1.3-1.6 mm,
      in the average of the deformed segments only. In the average of all segments, the
      above mean extensions are 0.7-0.9 mm, and with extra weights yield 0.8-1.4 mm.
      CONCLUSIONS: Just being suspended in water, due to the decompression, even
      without any extra weights, significant extension has been registered: a mean
      value of 1.0-1.2 mm per segments for the deformable, and 0.4-0.6 mm for all
      segments. The 20 minutes long treatment time in itself has a significant effect:
      the average additional extension is 0.2-0.4 mm per segments without, and about
      0.5 mm with extra weights. The deformation capacity of lumbar segments decreases
      with increasing age of patients. Elongations increase with increasing body
      height. Body weight shows different tendency depending on the sudden elastic and
      time-dependent viscous deformations. Significant difference has been observed in
      reaction time of male and female patients: female patients react later, however
      the final traction effect seems to be equal.

PMID- 11975046
TI  - Igenious impulses..

PMID- 11975047
TI  - Aftershocks.

PMID- 11975048
TI  - Wired for life.

PMID- 11975049
TI  - Following the leads.

PMID- 11975050
TI  - A body of work.

PMID- 11975051
TI  - Current controversy.

PMID- 11975052
TI  - Neuromuscular electrical stimulation in stroke rehabilitation.
AB  - We briefly review the literature related to the use of neuromuscular electrical
      stimulation (ES) in promoting recovery from stroke. ES can be used to facilitate
      motor learning in ankle dorsiflexion and wrist extension. It also has been shown
      to be beneficial in reducing shoulder subluxation but inconsistent in reducing
      shoulder pain. The mechanism of benefit of ES is unknown, but increased synaptic
      effectiveness has been suggested.

PMID- 11975053
TI  - Bringing back the nearly dead. The hope and the challenge.
AB  - Despite widespread use of cardiopulmonary resuscitation, sudden cardiac arrest
      outside of a hospital setting results in death most of the time. Hoping to
      improve resuscitation outcomes, University of Minnesota researchers have focused
      their efforts on understanding cardiopulmonary physiology and improving
      resuscitation technologies and procedures. This article describes new
      technologies, designed to be used in conjunction with standard CPR, that promote
      recovery from cardiac arrest. Active compression-decompression CPR, which
      involves use of a suction cup device to draw more blood into the heart and air
      into the lungs, has been shown to double 1-year survival rates. The inspiratory
      impedance threshold valve (ITV), when attached to an endotracheal tube or face
      mask, has been shown to increase cardiopulmonary circulation. An electrical
      stimulator device for the phrenic nerve, designed to evoke a gasp reflex, is
      under development. This device, when used in conjunction with the ITV, is thought
      to increase airflow into the lungs and blood flow into the heart, and may be
      beneficial for patients in hemorrhagic or heat shock as well as those in cardiac
      arrest.

PMID- 11975054
TI  - Medical malpractice insurance. Another crisis brewing?

PMID- 11975055
TI  - Electronic medical records.

PMID- 11975056
TI  - Adult pertussis prevalence.

PMID- 11975057
TI  - In search of a better mousetrap.

PMID- 11975058
TI  - [Evidence of evidence-based medicine?].

PMID- 11975059
TI  - [Medical necessity of psychotherapy is unquestionable. Combined position of AAGP,
      DGPM and DGPPN].

PMID- 11975060
TI  - [Pharmacotherapy of seasonal depression].
AB  - Seasonal affective disorder (SAD), first described in 1984, is a condition
      characterized by recurring depressive episodes in fall and winter alternating
      with nondepressive episodes in spring and summer. Various neurotransmitters have
      been implicated in the etiology of SAD, with the strongest evidence for an
      involvement of serotonin. Moreover, researchers have focused on the development
      of treatment modalities for SAD. Despite the proven efficacy of light therapy in
      SAD, some patients do not experience sufficient relief of depressive symptoms
      with light, and a number of them feel unable to comply because of logistical
      difficulties in administering bright light therapy. Comparatively few studies
      have examined the role of pharmacotherapy in the treatment of SAD. So far,
      selective serotonin reuptake inhibitors and possibly compounds with a distinct
      noradrenergic mechanism of action seem to be the treatment of choice for seasonal
      depression. There is, however, a clear need for further placebo-controlled
      studies to evaluate pharmacological treatment options for SAD.

PMID- 11975061
TI  - [Psychiatry as a profession].
AB  - With reference to Max Weber's timeless analysis of science and politics as a
      profession, the present paper describes the philosophical background and
      historical development of the tasks and tools, institutionalization, and
      socialization of psychiatry as a profession. In the mid twentieth century,
      psychiatrists' emergence from ideological confinement in asylums, where they were
      separated from urban culture and medicine in general, finally allowed them to
      benefit from accumulating knowledge and technological progress in the field of
      medicine. After its transition from a custodial to a therapeutic discipline,
      psychiatry has acquired a variety of new fields of action and duties that require
      a high degree of expertise on psychological and biological levels. At the same
      time, people have increasingly come to expect relief not only from disease, but
      also from manifold problems of everyday life. As a consequence, there has been an
      inflationary growth of professional psychiatric and psychotherapeutic and
      nonprofessional services. The professional requirements that psychiatrists should
      meet have also increased quantitatively and qualitatively in the wake of the
      historical change from a caring, paternalistic attitude towards the mentally ill
      to a therapeutic partnership. To a greater degree than physicians working in
      other medical fields, psychiatrists get personally involved with their patients.
      As a consequence, the mental burden of their profession is at times immense. For
      this reason, the ethics of a medical profession has special implications for
      psychiatrists. The fascinating advances in therapeutic methods, neurobiological
      knowledge, and the increasingly differentiated diagnostic tools, e.g.,
      noninvasive investigation of the morphology and functioning of the brain, have
      turned psychiatry into one of the most interesting contemporary professions.
      Psychiatry is now facing an enormous challenge of meeting the standards of
      expertise.

PMID- 11975062
TI  - [Psychopharmacotherapy of bipolar affective diseases].
AB  - The broadening of the classification systems for manic-depressive illness towards
      a spectrum of bipolar disorders implicates a more differentiated use of
      pharmacotherapies. However, many questions still remain open. This implies that
      all consensus guidelines and recommendations have to be considered as
      preliminary. On the other hand, research in the last decade has developed many
      new treatment alternatives, both for mood stabilizers and antidepressants as well
      as antipsychotics. These recommendations, which have been developed in the
      process of two consensus meetings, try to consider the broadening of the concept
      of bipolar disorder by differentiating between subgroups according to acute
      symptomatology and characteristics of the long-term course, e.g., rapid cycling.
      In particular, the emerging role and new indications of mood stabilizing
      antiepileptic drugs, atypical antipsychotics, and new antidepressants will be
      discussed.

PMID- 11975063
TI  - [The Werther effect. Significance, mechanisms, consequences].
AB  - The Werther effect is a highly regarded phenomenon in media effect research.
      Since the trail-blazing studies conducted by the American sociologist Phillips,
      there have been a great many attempts to quantify and evaluate imitative deeds
      that follow genuine suicides and apparent attempts at suicide. This paper starts
      by tracing the milestones along the way of research into the Werther effect. The
      concrete imitation patterns following suicides are then discussed, and the
      implications for responsible journalistic reporting that arise out of them are
      presented. This seems to be necessary, since despite many-sided and detailed
      findings on the Werther effect in Germany, there have so far been no experiments
      devoted to ways of exploiting these research results practically in a suicide
      prevention programme. Whilst in other countries preliminary guidelines for
      journalistic reporting have already been elaborated and in some countries even
      implemented, such efforts are still only in the very early stages in Germany.

PMID- 11975064
TI  - [Benzodiazepines and benzodiazepine-like anxiolytics and hypnotics. The
      implausible contraindication of closed angle glaucoma].
AB  - Official drug information materials mention angle-closure glaucoma as an absolute
      or relative contraindication for benzodiazepines, albeit with some unexplained
      variability. A systematic review of the literature reveals that this
      contraindication seems to be based on only one published case while 22 other
      investigations, some of them controlled, tend to favor that benzodiazepines
      reduce intraocular pressure. The common 1990-2001 database of the Drug Commission
      of the German Medical Profession and the Federal Institute for Drugs and Medical
      Devices contained one spontaneous report of glaucoma related to a benzodiazepine
      like hypnotic.

PMID- 11975065
TI  - [Establishing and changing therapeutic goals in psychiatric-psychotherapeutic
      treatment].
AB  - At the onset of psychotherapy, treatment goals are frequently not fully defined.
      They have to be set during treatment and can be changed in its course. An
      overview of the current literature on treatment goals from patients' and
      therapists' perspectives is given. Based on a case report of a patient suffering
      from panic disorder, the process of setting and changing goals and its influence
      on therapeutic technique and outcome are described. Finally, a case is made for
      the importance of "negotiations" between patient and therapist about treatment
      goals, which helps in building up a constructive therapeutic relationship and a
      helpful therapeutic process. The point in time of goal-setting, the achievability
      of treatment goals, and the patient's handling of unattained goals appear to be
      of particular significance.

PMID- 11975066
TI  - [Evaluation of therapeutic success by patients with anxiety disorders after
      inpatient psychotherapy].
AB  - OBJECTIVE: To identify factors influencing the subjective assessment of patients
      regarding the outcome of in-patient psychotherapy for anxiety disorders. METHODS:
      A total of 231 patients were tested at admission, discharge and 1-year follow-up
      in a multi-center study. Subjective outcome assessment was measured with the
      revised German version of the Helping Alliance Questionnaire. The use of the term
      "outcome satisfaction" is discussed. RESULTS: Patient outcome assessment did not
      correlate with age, sex, or education, or with duration or severity of illness or
      duration of treatment. Outcome assessment was closely connected with therapy
      success. Reaching a low symptom level ("clinical significance") had a higher
      impact than a high pre-post-difference ("statistical significance"). CONCLUSIONS:
      Anxiety patients give a generally positive assessment of their therapy outcome,
      which is most determined by symptom-related treatment success. The
      differentiation of "clinical" and "statistical significance" of success is of
      importance for the patient's subjective view of the therapy outcome.

PMID- 11975067
TI  - [Premenstrual dysphoric disorder. Recommendation for diagnosis of a distinct
      affective clinical picture].
AB  - In the research appendix of the Diagnostic and Statistical Manual of Mental
      Disorders (fourth edn.), premenstrual dysphoric disorder (PMDS) is classified as
      a cycle-related affective disorder. The cycle dependency of symptoms is the mean
      criterion for classifying this syndrome as a distinct etiological entity. These
      time-related criteria make special demands on diagnostic procedure, which must
      include retrospective and prospective elements. With our own study, we propose a
      three-step diagnostic process: (1) telephone screening, (2) retrospective
      diagnosis by a structured clinical interview, and (3) prospective diagnosis based
      on daily symptom ratings during two consecutive menstrual cycles. Following this
      procedure, the disorder could be verified in 4% of the original sample, which
      replicates the prevalence rate found in the literature.

PMID- 11975068
TI  - [Evaluation of olfactory stimuli by depressed patients].
AB  - Anhedonia, a cardinal sign of depression, is discussed to originate from a
      transmitter dysbalance in the central dopaminergic reward system. This system
      involves neuroanatomically many structures of the olfactory system. Hence the
      question arises whether anhedonia can be quantified when depressive patients
      judge smells hedonically. Sensory evaluation of olfactory stimuli by 16
      depressive patients was compared that of an age-matched control group. In the
      group comparison, mono- and birhinal sensory thresholds as well as judgment of
      intensity were not significantly different. For four of the eight smells, the
      hedonic judgements were found to be identical between the group of depressives
      and controls, with the remaining smells not significantly different. There were
      no differences in the consistency of ranking of smells. In a longitudinal (test
      retest) assessment there were again no differences in intensity, familiarity, and
      hedonic quality of the smells. The findings suggest that changes in the
      dopaminergic transmitter balance during the state of depression causing anhedonia
      affect neither olfactory perception nor the hedonic judgement of smells. Contrary
      to the clinical picture, anhedonia thus seems not to arise at the level of
      sensory perception yet but should be considered a more complex construct of
      disturbed central processing.

PMID- 11975069
TI  - [New kinds of relationships on the internet. Virtual object relations in
      psychotherapy].
AB  - Communication in the internet by e-mail is gaining in significance in counseling
      and psychotherapy of suicidal patients as well as an additional communication in
      face-to-face psychotherapy. E-Mail contacts during psychodynamic psychotherapy
      are defined as a transference offer of a virtual object relation. In two case
      descriptions of suicidal patients, examples of making contact with psychotherapy
      on the internet are presented. The concept of the virtual object is explained and
      its application for understanding these initial scenes and phenomena is
      discussed.

PMID- 11975070
TI  - [Self-help on the internet. Chances and risks of communication in electronic
      networks].
AB  - The worldwide web is used for self-help purposes by an increasing number of
      patients with a variety of mental disorders. The benefits and dangers of applying
      the internet in psychiatry are discussed based on a case report concerning a
      female with post traumatic stress and multiple personality disorders who visited
      a chat-room in the internet with two of her 48 supernumerary identities. During
      one stage of her history, she displayed an excessive use of the internet which
      must be considered a symptom of mental disorder rather than a distinct disease
      entity, viz. "internet addiction".

PMID- 11975071
TI  - [Psychiatry and the internet: possibilities, risks, perspectives].

PMID- 11975072
TI  - [Psychiatry as a profession--how does the future look?].

PMID- 11975073
TI  - [Thoughts on the value of computerized tomography in chronic rhinosinusitis].

PMID- 11975074
TI  - [Basic principles and concepts of enteral nutrition of ENT patients].
AB  - Patients suffering from head and neck cancer often show malnutrition even at the
      time of diagnosis. Therapeutic measures as surgery, radiation and antineoplastic
      chemotherapy additionally decrease the nutritional status. Therefore, an early
      supportive intervention is necessary in accordance to prognosis and quality of
      life. For many reasons, enteral nutrition has advantages to total parenteral
      nutrition. Percutaneous endoscopically guided gastrostomy (PEG) is the method of
      choice, for the application of enteral nutrition in most cases; special
      situations can be covered by using nasogastral feeding tubes, jejunostomy
      techniques, open surgical approach or radiologically guided gastrostomy. The
      industry provides a lot of different products suitable for nearly all patients.
      Furthermore, PEG facilitates the application of pharmacological agents, e.g.
      analgetics. However, the patient must be integrated in a network of professional
      care to ensure a safe nutrition therapy also in an outpatient setting.

PMID- 11975075
TI  - [Mucins in otorhinolaryngology].
AB  - BACKGROUND: Mucins are glycoproteins of high-polymer structure. They are an
      important component of the mucous layer covering the epithelia of the upper
      aerodigestive tract. Until now there has been little interest with regard to
      mucins in otorhinolaryngology. METHODS: The present knowledge about mucins of the
      upper aerodigestive tract is presented. A MEDLINE search was conducted for
      English- and German-language articles published from 1966 to the present.
      RESULTS: Thirteen different mucins named MUC 1-13 have been subdivided based on
      the classification system used by the Human Gene Mapping Committee. Besides
      mucins, small mucin-associated peptides, called trefoil factor peptides, have
      attracted much interest. CONCLUSIONS: Classification and attribution of the
      mucins found in the middle ear, larynx, oropharynx, esophagus, and nasolacrimal
      ducts has yet to be done. Also, little is known about the distribution of trefoil
      factor peptides in the upper aerodigestive tract.

PMID- 11975076
TI  - [Rational CT diagnosis before operations on the paranasal sinuses].
AB  - Movement or metal artefacts as well as the relatively high radiation exposure of
      both the axial and the coronal scan are disadvantages of computed tomography. A
      single spiral CT scan with a secondary reformation replacing the second CT scan
      might solve these problems. The goal of this project was to compare the
      diagnostic value of primary spiral CT scans of paranasal sinuses with secondary
      reformations. These were evaluated by ENT surgeons as well as radiologists. We
      performed axial and coronal spiral-CT's of paranasal sinuses in 80 patients. The
      secondary coronal and axial reformations were calculated with 2 mm image
      sections. Although a reduced resolution was observed in the secondary
      reformations, this did not compromise the detection of important anatomical
      features. Image deterioration due to artifacts was significantly reduced.

PMID- 11975077
TI  - [Parapharyngeal space-occupying lesions. Differential diagnosis based on case
      examples].
AB  - INTRODUCTION: Parapharyngeal tumors account for only 0.8% of all head and neck
      tumors which often presents the problem of preoperative diagnosis. Up to 80% of
      parapharyngeal tumors are benign. PATIENTS: Starting November 1995 to March 2001,
      16 patients with parapharyngeal tumors and 1 retropharyngeal abscess were
      treated. The median age was 54 years. Only 2 patients demonstrated peripheral
      nerve lesions preoperatively. RESULTS: 17 tumors and the retropharyngeal abscess
      were excised via transcervical approach, with an extension by parotidectomy and
      temporary mandibular split in 1 case. Histological entities were pleomorphic
      adenomas in 5 cases, a ganglioneurinoma, neurinoma of the vagal nerve and
      metastasis of a squamous cell carcinoma in 2 patients each, furthermore
      neuroblastoma, extramedullary plasmocytoma, T-cell lymphoma, and hemangioma in 1
      patient each. CONCLUSIONS: We demonstrate the differential diagnosis of
      parapharyngeal tumors as well as their diagnostic and therapeutic management. The
      tumors should be excised by a transcervical approach to protect cervical vessels
      and nerves, which is limited by a transoral approach.

PMID- 11975078
TI  - [Risk of postoperative hemorrhage in tonsillectomy. A comparison between general
      anesthesia and local anesthesia].
AB  - BACKGROUND: Postoperative bleeding after tonsillectomy is still a life
      threatening problem. The incidence of postoperative bleeding, as well as many
      factors (kind of surgery, hemostasic problems) affecting this risk have been
      investigated. A possible factor that has not been well studied is the used
      anaesthetic procedure. METHODS: A prospective study was completed comparing the
      risk of postoperative bleeding in patients operated in local vs. general
      anaesthesia. RESULTS: The study enrolled 1063 patients, who consecutively
      underwent tonsillectomy. In 16 (4.12%) of 388 patients operated under general and
      51 (7.55%) of 675 patients operated under local anaesthesia postoperative
      bleeding occurred. After local anaesthesia postoperative bleeding was seen mainly
      at the day of operation (46 of 51), there was no late bleeding after the 6th
      postoperative day. After general anaesthesia in 6 of 16 cases postoperative
      bleeding occurred after the 6th postoperative day. DISCUSSION: Postoperative
      bleeding occurs more frequent in patients who underwent tonsillectomy in local
      anaesthesia. The risk of late postoperative bleeding however is higher with
      tonsillectomy in general anaesthesia.

PMID- 11975079
TI  - [Force-based local navigation in robot-assisted implantation bed anlage in the
      lateral skull base. An experimental study].
AB  - Excellent precision, miss of retiring, reproducibility are main characteristics
      of robots in the operating theatre. Because of these facts their use for surgery
      in the lateral scull base is of great interest. In recent experiments we
      determined process parameters for robot assisted reaming of a cochlea implant bed
      and for a mastoidectomy. These results suggested that optimizing parameters for
      thrilling with the robot is needed. Therefore we implemented a suitable reaming
      curve from the geometrical data of the implant and a force controlled process
      control for robot assisted reaming at the lateral scull base. Experiments were
      performed with an industrial robot on animal and human scull base specimen.
      Because of online force detection and feedback of sensory data the reaming with
      the robot was controlled. With increasing force values above a defined limit feed
      rates were automatically regulated. Furthermore we were able to detect contact of
      the thrill to dura mater by analyzing the force values. With the new computer
      program the desired implant bed was exactly prepared. Our examinations showed a
      successful reaming of an implant bed in the lateral scull base with a robot.
      Because of a force controlled reaming process locale navigation is possible and
      enables careful thrilling with a robot.

PMID- 11975080
TI  - [Extramedullary plasmocytoma of the left tonsil. A rare cause of tonsillar
      asymmetry].
AB  - The plasmocytoma is a tumor, which can only rarely be found in the oropharynx. In
      this respective case an asymmetria of the tonsils was caused by an extramedullary
      plasmocytoma. Even if the asymmetria of the tonsils has a harmless nature, a
      tumor growth always has to be considered when thinking of the differential
      diagnosis. First of all, squamous-cell carcinoma has to be taken into account,
      more rarely with malignant lymphoma. Tonsillektomie added by immunhistological
      examination of the preparation brings diagnostic certainty.

PMID- 11975082
TI  - [Facial paralysis in mastoiditis. Facial paralysis in leukemic infiltration of
      the petrosal bone].

PMID- 11975081
TI  - [Pyoderma gangraenosum. Case report and comparison with necrotizing fasciitis].
AB  - The differential diagnosis of patients with ulcerative trachelophyma repeatedly
      causes difficulties. Particularly in view of the possibly fatal outcome, early
      differentiation between two clinical pictures is very important. Necrotizing
      fasciitis is often misdiagnosed or the diagnosis is delayed with a mortality rate
      of approximately 25-40%. It is characterized by local disintegration of the
      subcutaneous fascia and extensive gangrene of the skin. Sometimes it is not even
      possible to control the disease using combined antibiotics. Early surgical
      exploration is mandatory to stop progression of the disease. Pyoderma gangrenosum
      develops following an initial lesion with pustules and bullae in an ulceration
      with slight bleeding. Therapy consists of i.v. glucocorticoids (60-200 mg
      prednisolone/day) administered as early as possible. In complete contrast to the
      therapy for necrotizing fasciitis, surgical intervention should be strictly
      avoided in cases of pyoderma gangrenosum.

PMID- 11975083
TI  - [Recurrent sialadenitis of the submandibular gland. Normal variant of Wharton
      duct of the left submandibular gland].

PMID- 11975084
TI  - [Legal liability of a pop concert manager in noise trauma. Decision of the
      Koblenz district supreme court 13 September 2001 (Az 5 U 1324/00)].

PMID- 11975085
TI  - [Indications for neck operation in undetected lymph node metastases. 1: Basic
      principles of lymphogenic metastatic behavior of otorhinolaryngology cancers].

PMID- 11975086
TI  - [Modern nuclear magnetic resonance techniques in stroke].
AB  - In industrialized nations, stroke is the most common cause of permanent
      disability and need of care. Causal treatment is possible only during the first
      few hours following the stroke, in the form of systemic fibrinolysis. An exact
      diagnosis of the causative pathology must be made before starting the therapy,
      and this must happen in the shortest possible period of time. Using imaging
      techniques, the whole spectrum of differential diagnoses of cerebral ischemia
      must be covered, including above all intracerebral and subarachnoid hemorrhage.
      Although computed tomography (CT) is excellently suited for determining
      hemorrhage, infarct can be recognized with much better contrast using diffusion
      weighted magnetic resonance (MR) imaging (DWI). Stroke MR imaging additionally
      allows the representation of vital "tissue at risk" of infarction using perfusion
      images as well as the recognition of vessel occlusion using MR angiography. This
      paper is intended to define the usefulness of DWI in comparison to CT techniques
      and to elucidate the use of diffusion coefficients for differentiating the
      various stages of infarction. Besides presenting an explanation of the basic
      principles of modern stroke MR imaging, typical results of MR perfusion
      measurements and the appearance of hemorrhages on MR will be explained.

PMID- 11975087
TI  - [Intravenous immunoglobulins in multiple sclerosis. Studies and mechanisms of
      action--an update].
AB  - There is no doubt about the immunomodulatory capacity of intravenous
      immunoglobulins (IVIg). This also holds true for multiple sclerosis (MS), where
      clinical trials have shown a reduction in relapse rate and number of active
      lesions on MRI after IVIg treatment. Experimental data in the model of murine
      Theiler's virus encephalomyelitis (TMEV) gave rise to the hypothesis that IVIg
      may also promote remyelination. Unfortunately, recent trials were unable to
      demonstrate clinically relevant remyelination in MS patients treated with IVIg. A
      possible explanation could lie in the fact that IVIg do not influence the
      function of oligodendrogilial cells in vitro. In contrast, IVIg can protect
      oligodendrocytes against complement-mediated injury and thus provide more cells
      that could engage in remyelination. In addition, IVIg can modulate microglial
      functions in vitro, thus creating a microenvironment permissive for
      remyelination. Should such mechanisms also be operative in vivo, they would have
      escaped detection in the treatment protocols used to date. It would appear that
      IVIg need to be administered while the inflammatory process is still ongoing,
      whereas the published trials included only patients with a stable deficit when
      there is probably little or no active inflammation. Despite new studies on IVIg,
      its role in the management of MS remains elusive.

PMID- 11975088
TI  - [Clinical relevance of detection of microembolism signals with transcranial
      Doppler ultrasound diagnosis].
AB  - Detection of microembolic signals (MES) has been described in several patients
      groups. A potential clinical relevance of this technique has been established (1)
      during the first hours following carotid endarterectomy and (2) for patients with
      asymptomatic ICA stenosis or various autoimmune disorders. Intraoperative
      monitoring in patients undergoing cardiac or carotid surgery can be used to
      improve the surgical technique but provides no prognostic information for
      individual patients. Microembolic signals in patients with prosthetic heart
      valves cannot be used as markers for stroke risk; their potential significance as
      markers for neuropsychological deficits remains unclear. Recent reports suggest
      that MES can be used as surrogate markers for assessing the efficacy of
      antiplatelet agents. The fact that automated MES detection is not feasible
      greatly reduces the technique's applicability. On the whole, MES detection--with
      the exception of the patient groups listed above--provides pathophysiological
      rather than clinically relevant information.

PMID- 11975089
TI  - [Laboratory diagnosis of hyperkinetic movement disorders in adulthood].
AB  - Hyperkinetic movement disorders such as dystonia, chorea, ballism, myoclonus,
      tics, and tremor may be idiopathic or symptomatic in origin. Symptomatic movement
      disorders need further diagnostic testing in order to identify their etiology. In
      addition to clinical findings, imaging techniques, and electrophysiological
      testing, laboratory studies are required. Here, we review the prevalence of
      diseases presenting with symptomatic hyperkinetic movement disorders and discuss
      the diagnostic relevance of laboratory studies.

PMID- 11975090
TI  - [The Multiple Sclerosis Documentation System MSDS. Discussion of a documentation
      standard for multiple sclerosis].
AB  - The MSDS (multiple sclerosis documentation system) has been developed at the
      Department of Neurology, Technical University of Dresden, Germany, during the
      last 4 years. The first version of this database application has been in use
      since October 2000. The MSDS manages information on MS patients, their treating
      physicians, patient history (symptoms, other diseases, biographical history,
      family history, habits, medication), clinical signs, results of laboratory
      examinations (blood chemistry, autoantibodies, borrelia serology, evoked
      potentials, cranial and spinal cord magnetic resonance imaging), clinical scores
      relevant for MS, and biosamples. In principle, MSDS allows online data input and
      semiautomatically generates reports to all general practitioners and neurologists
      treating the respective patient. Patient information sheets and internal
      treatment guidelines are part of the system. During a 3-month evaluation, the
      first version of MSDS was tested at eight university multiple sclerosis
      ambulatory care units and one general neurology hospital. The overall judgement
      was favorable. Suggestions for changes and improvements, as well as practical
      experiences, were considered when developing MSDS 2.0, which will be available by
      the end of 2001.

PMID- 11975091
TI  - [Analgesic effect of the selective noradrenaline reuptake inhibitor reboxetine].
AB  - BACKGROUND: Reboxetine is a selective noradrenaline reuptake inhibitor (NARI). As
      noradrenaline plays a relevant role in antinociceptive mechanisms, the hypothesis
      was investigated in this study whether reboxetine has analgetic efficacy.
      METHODS: Twenty-four healthy volunteers were investigated in a crossover design.
      Reboxetine (2 x 2 mg) or placebo were given for 5 days with the "crossover"
      following a one-day washout in between. The primary end-points were the N1 and P2
      amplitudes of laser evoked somatosensory potentials (laser SEP) of vertex EEG. In
      addition, visual analogue scales (VAS, 100 mm) were used. RESULTS: Reboxetine
      showed a higher analgesic potency than placebo, with a statistically significant
      superiority in capsaicinirritated skin--in the objective tests (laser SEP, P <
      0.0001 for N1 and P = 0.0002 for P2) as well as in the subjective pain
      measurements (VAS, P < 0.0003). Besides pain, the subjective feelings of burning
      and itching were lower with reboxetine than with the placebo. CONCLUSIONS: The
      hypothesis that a selective noradrenergic substance could be of analgesic
      efficacy was proven the first time experimentally. Reboxetine reduced the N1 and
      the P2 components of the laser SEP, which speaks for central and peripheral
      mechanisms of action.

PMID- 11975092
TI  - [Use of magnetoencephalography and functional neuronavigation in planning and
      surgery of brain tumors].
AB  - The role of magnetoencephalography (MEG) in neurology has been established for
      basic research, epilepsy, and functional brain mapping. The presurgical
      localization of functionally important brain areas has evolved as an important
      application of MEG. Both neurologists and neurosurgeons can use this method for
      decision-making and planning of nonsurgical or surgical treatment in brain
      tumors. The integration of functional brain mapping data into neuronavigation
      systems may help to minimize postoperative morbidity. This is especially
      important in low-grade gliomas, in which a potential benefit of surgery is only
      achieved when the tumor has been resected completely, whereas neurological
      deterioration means a substantial loss of quality of life during the survival
      time. This report addresses the utility of MEG combined with neuronavigation in
      the treatment of brain tumors adjacent to eloquent brain areas.

PMID- 11975093
TI  - [Dysequilibrium in idiopathic Parkinson disease. The effect of cerebrovascular
      comorbidity].
AB  - Disturbance of balance in idiopathic Parkinson's disease (IPD) has a significant
      effect on disability. Yet the underlying mechanisms and the contribution of age
      associated comorbidity to dysequilibrium are unclear. In this study, static
      posturography was performed in 30 healthy controls and 40 patients with IPD.
      Comparison of sway during quiet stance did not show significant differences
      between patients and controls. Multiple linear regression analysis was used to
      identify factors responsible for the considerable interindividual variance in
      patients. Results of the pull test, CT-verified cerebral microangiopathy,
      dementia, and age were assessed, but only cerebrovascular comorbidity contributed
      significantly to variance. Apart from increased sway, patients with coinciding
      cerebral microangiopathy (n = 20) more frequently had a history of falls or
      pathological responses in the pull test. The present results suggest that
      cerebrovascular comorbidity enhances dysequilibrium in IPD. Pathological sway in
      IPD can indicate comorbidity and may have implications for further diagnostics.

PMID- 11975094
TI  - [Clinical presentation and prognosis of brain stem infarcts. An evaluation of the
      Stroke Databank of the German Stroke Foundation].
AB  - Due to the great variety of clinical classification systems and syndromes, a
      representative overview of the etiology and prognosis of brain stem infarctions
      is missing. From the German Stroke Data Bank we therefore investigated 455
      patients with visible brainstem infarction on cerebral imaging in comparison to
      patients with other infarct localizations. Follow-up after 3 and 12 months
      assessed functional outcome and recurrence of cerebral ischemia. Of 455 patients
      with acute brainstem infarction, 115 had additional infarctions in other vascular
      territories. In the remaining 340 patients with isolated brainstem infarction,
      the classification was: small vessel disease in 36.2%, macroangiopathy in 22.6%,
      and cardioembolism in 11.2%. After 3 months, 10% of the patients with isolated
      brainstem infarction had died and 55.6% were functionally independent. Mortality
      was 43.5% in patients with combined brainstem infarction. Our study highlights
      the frequency of small vessel disease as well as the relatively favorable
      prognosis in isolated brainstem infarction and preserved consciousness.

PMID- 11975095
TI  - [External ophthalmoplegia caused by amitriptyline poisoning].
AB  - Drug-induced ocular motor disorders occurring during coma may be difficult to
      distinguish from structural cerebral lesions. We recently encountered a case of
      reversible amitriptyline-induced external ophthalmoplegia, which was first
      described by Mladinich and Carlow in 1977. We suggest that the mechanism for gaze
      paresis and loss of vestibulo-ocular reflex due to amitriptyline overdose
      involves the modulation of neurons of the pontine paramedian reticular formation,
      the rostral fasciculus longitudinalis medialis, and the vestibulo-ocular reflex.
      Clinical features that might be useful when distinguishing amitriptyline-induced
      ophthalmoplegia from structural brain lesions--such as basilar thrombosis-
      include the preservation of corneal response, purposeful withdrawal from noxious
      stimuli, rapid recovery within 24 hours, and the reversal of symptoms by
      physostigmine.

PMID- 11975097
TI  - [Lipomatosis dolorosa--a frequently overlooked disease picture].
AB  - Dercum's disease (lipomatosis dolorosa) is a relatively unknown illness. The
      disorder usually affects middle-aged females. Subcutaneous fatty tissue deposits
      may occur in many parts of the body. The upper arms, elbows, stomach wall,
      buttocks, thighs, or knees are most commonly affected. Severe hyperalgesia is
      found on light pressure and touch. Analgesics or pain-modulating drugs usually
      have little or no effect. The following case report demonstrates successful
      symptomatic treatment of the otherwise nearly unbearable complaints: intravenous
      infusions of 5 mg/kg body weight of lidocaine over 30-90 min may give pain relief
      lasting several weeks or even months. Alternatively, patients are treated with
      150-750 mg orally administered mexiletine daily. Surgical excision or liposuction
      of these fatty tissue deposits have shown significant reduction of pain. However,
      this effect reduces over time and recurrences often develop.

PMID- 11975096
TI  - [Glioblastoma multiforme as a manifestation of Turcot syndrome].
AB  - Turcot's syndrome, clinically characterized by the coincident occurrence of
      primary tumors of the colon and the central nervous system, can genetically be
      divided into two syndromes: familial adenomatous polyposis (FAP) and hereditary
      nonpolyposis colon carcinoma (HNPCC). In the present case, a 60-year-old patient
      with glioblastoma multiforme and a history of hereditary malignomas is described
      as an example of a HNPCC-associated Turcot's syndrome. New molecular biological
      methods and results give deeper insight into clinical syndromes, and the better
      understanding improves diagnostics, therapy, and outcome estimations, even in
      rare diseases. In the present case, a new germinal mutation could be identified.

PMID- 11975098
TI  - [Goose flesh and cold sensation. Symptoms of visceral epilepsy].
AB  - Goose flesh and cold shiver can be ictal signs of visceral epilepsies. These
      visceral epilepsies may occur with isolated ictal signs during a simple partial
      seizure or in combination with other autonomic signs or in complex partial
      seizures. Because of the unusual features of the ictal symptomatology, these
      visceral epilepsies often are masked and wrongly diagnosed as nonepileptic
      events, e.g., somatoform disorders. Five cases are reported with case history,
      neurological findings, and results of electroencephalography, MEG, and imaging.
      Interestingly, patients did not suffer from tumoral epilepsies and the epileptic
      focus was lateralized to the left (dominant) temporal lobe.

PMID- 11975099
TI  - [Initial experiences with clinical use of botulinum toxin type B].
AB  - Recently, botulinum toxin type B (BT-B) was introduced for treatment of cervical
      dystonia (CD). We wish to report on experience with BT-B derived from
      registration studies and from our own preliminary clinical experience. Botulinum
      toxin type B can be used successfully in CD patients with antibody-induced
      failure of botulinum toxin type A therapy (antibody patients). In our own 15
      antibody patients, 11835 +/- 2,039 mouse units of BT-B (NeuroBloc) reduced the
      Toronto Western spasmodic torticollis rating scale (TWSTRS) score from 20.5 +/-
      3.6 to 13.1 +/- 5.4. BT-B can also be used successfully in CD patients not
      previously exposed to BT-A or BT-B (de novo patients). In our own nine de novo
      patients, 10436 +/- 3,320 mouse units of BT-B reduced the TWSTRS score from 18.4
      +/- 5.4 to 9.2 +/- 4.8. Altogether, dryness of the mouth occurred in 21 CD
      patients (severe 10, moderate 7, mild 4), accommodation difficulties in seven,
      conjunctival irritation in five, reduced sweating in four, swallowing
      difficulties in three, heartburn in three, constipation in three, bladder voiding
      difficulties in two, and dryness of nasal mucosa, head instability, and thrush in
      one each. BT-B produces substantially more systemic autonomic side effects than
      BT-A. It can be considered the therapy of choice in antibody patients. For de
      novo patients and for BT-A-treated CD patients, BT-B cannot be recommended
      currently.

PMID- 11975100
TI  - [Gabriel Anton (1858-1933). Comments on the issue cover picture].

PMID- 11975101
TI  - Answer to case of the month #85: abdominal computed tomographic manifestations of
      cystic fibrosis in an adult.

PMID- 11975103
TI  - Practice audit program. Radiology reporting audit record form.

PMID- 11975102
TI  - Radiology reporting handbook.

PMID- 11975104
TI  - Self-assessment program. Radiology reports: April-November 2002.

PMID- 11975105
TI  - Non-Hodgkin's lymphoma in patients with systemic lupus erythematosus: 2 case
      reports.

PMID- 11975106
TI  - Computed tomography to detect body packing: an unusual cause of small bowel
      obstruction.

PMID- 11975107
TI  - Is routine micropuncture access necessary for percutaneous nephrostomy? A
      randomized trial.
AB  - OBJECTIVE: To compare the micropuncture technique and the conventional large-bore
      needle approach for renal access. METHODS: From July 1999 to July 2000, patients
      referred to interventional radiology for emergent or elective percutaneous
      nephrostomy with normal coagulation profiles were considered for the study.
      Nephrostomy procedures were performed using a micropuncture system or large-bore
      needle for collecting system access; 24 nephrostomy procedures were randomized to
      each group using permuted blocks and opaque sealed envelopes. Gross hematuria,
      quantitative urine red blood cell counts, pain scores and procedural success were
      compared between the 2 groups. RESULTS: There was a small difference in the
      incidence of gross hematuria between the large-bore needle and micropuncture
      groups (12 [50%] v. 8 [33%] patients), but this difference was not statistically
      significant. Quantitative urine red blood cell counts obtained immediately after
      and 24 hours after nephrostomy placement showed no significant differences.
      Significantly fewer needle passes were required for access in the large-bore
      needle group than the micropuncture group (1.7 v. 2.8, p = 0.01), and mean
      procedure duration was 7 minutes longer in the micropuncture group, although this
      difference was not significant. No differences in pain scores or procedure
      success were seen. CONCLUSION: Percutaneous nephrostomy performed with a
      micropuncture system in patients with normal coagulation profiles does not
      significantly decrease organ bleeding or pain. More needle passes and
      manipulations are required, which may increase procedure duration. The additional
      costs of routine micropuncture access for percutaneous nephrostomy are not
      supported by this study.

PMID- 11975108
TI  - Usefulness of the skyline view in the assessment of acute knee trauma in
      children.
AB  - We report a retrospective analysis of all cases of acute knee injuries in
      children presenting to the Winnipeg Children's Hospital, University of Manitoba,
      between Jan. 1, 1994, and Jan. 1, 1995. The mechanism of injury was recorded and
      all 3 radiographic views (i.e., anterioposterior, lateral and skyline) were
      available for 171 of 256 total cases. We found a significant association between
      mechanism of injury and visualization of damage on skyline view radiographs (p <
      0.01). The skyline view showed damage in only 1 of the 158 cases involving direct
      or indirect injury not involving subluxation or dislocation. However, damage was
      visualized on skyline view radiographs in 7 (54%) of the 13 cases that included a
      history of subluxation or dislocation. We conclude that in acute knee trauma in
      children, a skyline view radiograph of the patella should be obtained only when
      the mechanism of injury includes subluxation or dislocation. When the mechanism
      does not suggest subluxation or dislocation, the skyline view is unlikely to
      reveal damage; it adds unnecessary radiation, cost and possible added discomfort
      for the child.

PMID- 11975109
TI  - The developing stroke: management decisions.
AB  - Radiologists have become important members of a multidisciplinary team aimed at
      treating stroke. New studies such as the NINDS (National Institute of
      Neurological Disorders and Stroke) intravenous and PROACT II (prolyse in acute
      cerebral thromboembolism II) intra-arterial thrombolytic trials for acute stroke
      have focused attention on the need for rapid management. Radiologists play a key
      role in the diagnosis and selection of patients who may benefit from these
      therapies. We review current issues in the computed tomographic and magnetic
      resonance imaging diagnosis of acute stroke and the data supporting the various
      treatment options.

PMID- 11975110
TI  - [Immunoablation or otherwise followed by hematopoietic cell stem as intensive
      treatment of severe autoimmune diseases].
AB  - The treatment of severe autoimmune diseases has been recently revitalized by the
      increasing utilization of clinical interventions aimed at ablating/abrogating
      autoimmune lymphoid clones followed (but not in certain procedures) by
      transplantation of allogeneic, but also autologous, hematopoietic stem cells. Two
      different investigative avenues have paved the way to specific clinical studies.
      The first originates from the epochal murine experiments of the '70s, and has
      been greatly expanded in the last decade. A graft-versus-autoimmunity effect
      could also be demonstrated. In addition, it could also be shown that induced
      experimental autoimmune diseases such as adjuvant arthritis and autoimmune
      encephalomyelitis could, surprisingly, be cured following autologous
      transplantation. The first results in humans were observational and derived from
      studies including patients with coincidental diseases (severe autoimmune diseases
      plus leukemia/aplasia) treated with allogeneic hematopoietic stem cell
      transplants. Although the concept of an allogeneic transplant is indisputably
      more appealing, very few patients with an isolated severe autoimmune disease have
      been treated using such a therapeutic approach. Reduced intensity conditioned
      transplants relying on subsequent graft-versus-autoimmunity effects strengthened
      by donor lymphocyte infusions are being explored cautiously. On the other hand,
      autologous transplants are being performed quite extensively. To date,
      transplanted severe autoimmune diseases include multiple sclerosis, connective
      tissue diseases (systemic sclerosis, systemic lupus erythematosus, rheumatoid
      arthritis) and many others. It is uncertain if the main mechanism is solely
      immunoablative, or whether tolerized lymphocytes may also develop during a
      postulated "window of opportunity" following the transplant.

PMID- 11975111
TI  - [Logical structure of the problem oriented clinical record. A combined Popper
      Bayes approach].
AB  - The problem-oriented medical record is a tool whose correct compilation meets the
      requirements of the law as well as the need for continuing medical education
      within the logic of clinical decision making. The reading of the contents of a
      record allows people to evaluate the correspondence between the "thinking" and
      the "doing" of a doctor, as well the objectivity of the facts--that is, the truth
      related to the reasons for a patient's admission to hospital and the nature of
      his or her illness. To this aim, the authors suggest a structural logical iter in
      concordance with the lines of hypothetical-deductive epistemology, in contrast to
      inductive epistemology, as tradition has always suggested. The latter, in fact,
      proposes to start from singular observations and proceeding, by successive steps,
      towards a diagnosis. It thus neglects to take error into consideration, and
      therefore the differential diagnostic process, and ignores the fact that one
      cannot pass from single descriptions to universal (diagnostic) laws on the basis
      of logic. The process of falsification therefore plays a central role in the
      diagnostic procedure and thus in the construction of the medical record. This
      falsification process is centered, according to the most recent epistemology, on
      the logical schemes of Popper-Hempel and Bayes. The authors propose an integrated
      combination of both schemes to enable a correct approach to diagnostic hypothesis
      and to differential diagnosis, with their relevant legal, didactic and
      administrative repercussions.

PMID- 11975112
TI  - Obtaining good quality medical information from the World Wide Web.
AB  - Despite the complexity of the Internet, it is surprisingly easy to search the
      World Wide Web for medical information. With the right skills you can save
      yourself a lot of time and effort making the Internet a highly effective tool for
      supporting your work in health and medicine. Internet offers great opportunities
      for interactive learning and can help you to plan lectures and create teaching
      materials. Moreover, physicians can find many Web resources that can assist with
      articles and assignments and support academic research. Evidence-based
      indications about medical treatments are also available. However, Internet users
      need to be aware of the dangers of misleading and inaccurate medical information.
      In this article, we intend to illustrate to physicians the pros and cons of the
      World Wide Web, how to apply basic critical appraisal techniques to gather good
      quality medical information, and a number of useful medical Web sites.

PMID- 11975113
TI  - [Gastric protection against non-steroidal and steroidal antiinflammatory agents
      in internal medicine specialties: survey on prescription trends among hospital
      internal medicine physicians (Gardenia Project)].
AB  - Hospital physicians employed in 37 departments of medicine in the Regions of
      Campania and Molise were asked to reply to a questionnaire aimed at evaluating,
      among their inpatients, the real extent of gastrointestinal side effects caused
      by nonsteroidal anti-inflammatory drugs and steroids, and to point out which
      gastroprotective drugs they thought were preferable in various clinical
      situations. In this way, a study group of internists has gathered information
      about the outlook of internists towards gastroprotection; they have also
      calculated the pharmacoeconomic burden of these measures.

PMID- 11975114
TI  - Relapsing pure red cell aplasia associated with B-cell chronic lymphocytic
      leukemia successfully treated by intravenous immunoglobulin concentrate.
AB  - Pure red cell aplasia (PRCA) is a rare syndrome characterized by a normochromic
      normocytic anemia and the absence of mature erythroid precursors in an otherwise
      normocellular bone marrow. Acquired PRCA has been associated with autoimmune,
      viral or neoplastic conditions. We report the case of a patient with B-cell
      chronic lymphocytic leukemia (B-CLL) and PRCA. Conventional antileukemic
      treatment had no effect on the PRCA, while the B-CLL showed partial remission
      according to the International Workshop on Chronic Lymphocytic Leukemia response
      criteria. The patient was treated with cyclosporin A that resulted in complete
      response of the PRCA lasting 12 months. PRCA relapse, suggested by a hemoglobin
      decrease and by bone marrow biopsy, did not respond to prednisone and
      cyclophosphamide treatment. Fludarabine treatment was started in July 1999; the B
      CLL remained stable according to the International Workshop on Chronic
      Lymphocytic Leukemia response criteria, the PRCA did not improve. In October
      1999, because of intercurrent pneumonia, the patient was treated with intravenous
      immunoglobulin (IVIG) concentrate. This treatment resulted in total resolution of
      the pneumonia and a complete response of the PRCA. Therefore the patient remained
      on monthly IVIG. In view of the known efficacy of IVIG in the treatment of PRCA
      induced by parvovirus B19 and since serial polymerase chain reaction
      determinations of parvovirus B19 were repeatedly negative in our subject, we
      hypothesize that the IVIG per se may have a therapeutic effect on PRCA. The
      present case suggests that IVIG may be of benefit for PRCA patients even if the
      disease is unrelated to parvovirus B19 infection.

PMID- 11975115
TI  - Heparin-induced life-threatening hyperkalemia.
AB  - Hyperkalemia may occur in many clinical settings and lead to serious events.
      Heparin-induced hyperkalemia is presumably less well recognized than other
      untoward effects of heparin treatment and more frequent than commonly perceived.
      To draw attention to this clinically relevant occurrence, we report 2 cases of
      life-threatening bradyarrhythmia associated with heparin prescription. Heparin
      induced hyperkalemia is mediated by an enzymatic block in the synthesis of
      aldosterone; however, in most cases severe hyperkalemia occurs in the presence of
      additional factors influencing potassium homeostasis. Patients treated with
      heparin should be stratified and adequately monitored according to the outlined
      risk profile.

PMID- 11975117
TI  - Blastocystis hominis and blastocystosis (Zierdt-Garavelli disease).

PMID- 11975116
TI  - Human herpesvirus type 8-associated primary lymphomatous effusion in an elderly
      HIV-negative patient: clinical and molecular characterization.
AB  - Primary lymphomatous effusions are defined as lymphomas presenting in the serous
      body cavities in the absence of clinically identifiable tumor masses. Recently, a
      peculiar type of primary lymphomatous effusion associated with tumor clone
      infection by human herpesvirus type 8 (HHV-8) and preferentially arising in HIV
      positive patients has been described and termed as primary effusion lymphoma
      (PEL). This report describes a case of PEL which has developed in a HIV-negative,
      92-year-old man with longstanding Mediterranean Kaposi's sarcoma, a disease also
      associated with HHV-8 infection. The patient presented with pleural and ascitic
      effusions in the absence of solid masses within the lungs, mediastinum, thoracic
      wall or abdominal cavity. The effusions consisted of malignant lymphocytes with
      morphologic features bridging immunoblastic and anaplastic cells.
      Immunophenotypic studies revealed that the lymphoma population expressed an
      antigenic profile consistent with PEL, i.e. the absence of common B- and T-cell
      markers (non-B, non-T phenotype) coupled to CD138 positivity. Molecular analysis
      demonstrated infection of the tumor clone by HHV-8 as well as monoclonally
      rearranged immunoglobulin genes, consistent with a B-cell histogenesis of the
      lymphoma. In addition, this PEL case harbored PAX-5 gene mutations, which have
      been recently demonstrated as a key feature of the proto-oncogene hypermutation
      process involved in the pathogenesis of some lymphoma types. Following two
      courses of etoposide and prednisone, a partial remission was achieved. The
      patient died of liver failure 3 months after the diagnosis of PEL. Overall, this
      case report illustrates the need for an integrated diagnostic approach based on
      clinical features, morphology, immunophenotype, and molecular genetics to primary
      lymphomatous effusions.

PMID- 11975118
TI  - [Inhibition of nasal nitric oxide in patients with allergic rhinitis].

PMID- 11975119
TI  - [The World Wide Web and medical information].

PMID- 11975120
TI  - High-dose intravenous immunoglobulin therapy for immune-mediated disorders. Only
      immunoglobulins?

PMID- 11975121
TI  - Diabetes epidemic surging. New consumer campaign targets blood glucose, blood
      pressure, cholesterol.

PMID- 11975122
TI  - ACOG supports epidural pain relief on demand.

PMID- 11975123
TI  - Understanding dietary supplement regulation. Expressing concern as use continues
      to rise.

PMID- 11975124
TI  - Olive oil. A natural treatment for sore nipples?

PMID- 11975125
TI  - Recognizing heart disease. Helping women seek treatment faster.

PMID- 11975126
TI  - The bottom line. Learning to speak the language of finance.

PMID- 11975127
TI  - Cystic fibrosis carrier screening. Are nurses ready to be on the front line?

PMID- 11975128
TI  - The "silent" disease. Diagnosing & treating depression in women.

PMID- 11975129
TI  - College-bound sisters. Exploring one pregnancy prevention program.

PMID- 11975130
TI  - Childbearing among diverse populations. How one hospital is providing
      multicultural care.

PMID- 11975131
TI  - AWHONN partners with national cervical cancer campaign.

PMID- 11975132
TI  - Memories of a loved one. From caring comes comfort.

PMID- 11975133
TI  - Mandatory staffing ratios: a dilemma.

PMID- 11975134
TI  - Circumcision decisions.

PMID- 11975135
TI  - Depo-Provera.

PMID- 11975136
TI  - Battered & pregnant. A nursing challenge.

PMID- 11975137
TI  - Diet and physical activity recommendations and compliance issues for South
      Carolina children and adolescents.

PMID- 11975138
TI  - Differences in diet quality among fourth and seventh grade public school students
      in South Carolina.
AB  - The purpose of this study was to compare various aspects of diet quality between
      fourth graders and seventh graders. Consumption in each food group and food
      variety pattern suggested that dietary quality of fourth graders and seventh
      graders were different. Fourth graders showed "better" dietary behaviors than
      seventh graders with some variations among food groups and differences regarding
      gender. Importantly, it should be noted by the health care community that diet
      quality tends to decline with the progression from childhood to early
      adolescence. These same concerns are mentioned in the previous paper, i.e., the
      declining quality of diet with increased age in moving from childhood to
      adolescence. Specific areas that should be targeted for improvement were
      identified. The information obtained from this study suggests the need for
      renewed efforts by physicians, health educators, nutritionists, and policy makers
      to improve the diet quality of children and adolescents. In addition, this
      information is vital for formulating the appropriate and effective private
      provider and public health interventions and prevention initiatives to improve
      the health and wellness of South Carolina youth as they progress from childhood
      to adolescence into adulthood.

PMID- 11975139
TI  - Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy
      in South Carolina: the MUSC experience (1999 through 2001).

PMID- 11975140
TI  - Patient use of automatic blood pressure measures in retail stores: implications
      for diagnosis and treatment of hypertension.
AB  - This study examined the simple behavior on the part of hypertensive patients of
      having their blood pressure checked at a retail store. We found that hypertensive
      patients checked their blood pressure frequently using these automated machines,
      believe them to be accurate, and frequently make health care decisions based on
      the reading they obtain. The inaccuracy of these machines is apparently not
      widely known. It is therefore incumbent on physicians to be aware of technologies
      that are in use by their patients. Patients need to be educated about the
      appropriate use and potential or harm that results from misuse of these
      technologies. Physicians might encourage their patients to invest in a home blood
      pressure monitor that they can bring with them to their visit to calibrate
      against the physician's own machine.

PMID- 11975141
TI  - Price survey. Generic drug market heats up.

PMID- 11975142
TI  - Deadline looms for reuse rules; hospitals are wary.

PMID- 11975144
TI  - Instrument repair often misunderstood.
AB  - Hospitals throw away--literally--millions of dollars worth of surgical
      instruments each year, for no other reason than ignorance of their actual value.
      Meanwhile, the cost of repairing others exceeds their actual value. That's the
      assessment of one industry veteran, and he may well be right, considering the
      reaction of a group of materials managers who met with him recently.

PMID- 11975145
TI  - Tradition and change.

PMID- 11975146
TI  - Second-order backward blocking and unovershadowing in human causal learning.
AB  - De Houwer and Beckers (in press, Experiment 1) recently demonstrated that ratings
      about the relation between a target cue T2 and an outcome are higher when
      training involves CT1+ and T1T2+ followed by C+ trials than when training
      involves CT1+ and T1T2+ followed by C- trials. We replicated this study but now
      explicitly asked participants to rate the causal status of the cues both before
      and after the C+ or C- trials. Results showed that causal ratings for T2 were
      significantly higher after C+ trials than before C+ trials and that T2 received
      significantly lower ratings after C- trials than before C- trials. The results
      thus provide the first evidence for higher-order unovershadowing and higher-order
      backward blocking. In addition, the ratings for T1 revealed that first-order
      backward blocking (i.e., decrease in ratings for T1 as the result of C+ trials)
      was stronger than first-order unovershadowing (i.e., increase in ratings for T1
      as the result of C- trials).

PMID- 11975147
TI  - Process-dissociation procedure: a testable model for considering assumptions
      about the stochastic relation between consciously controlled and automatic
      processes.
AB  - This paper presents an extension of the process-dissociation procedure with
      wordstem completion, which makes possible the measurement of the stochastic
      relationship between consciously controlled and automatic processes. By means of
      an indirect wordstem completion test, the conditional probabilities of conscious
      remembering with and without automatic processes can be successfully determined.
      A multinomial model for the evaluation of this extended process-dissociation
      procedure is presented. This model makes the distinction between voluntary and
      involuntary conscious memory processes possible and has been applied to two
      experiments discussed in this paper. The results show that the assumption of
      stochastic independence is often violated, albeit not as strongly as predicted by
      the redundancy or exclusivity model variants. Two conscious processes were found,
      voluntary and involuntary conscious memory processes, each with a different
      probability of occurrence.

PMID- 11975148
TI  - Comprehending spoken metaphoric reference: a real-time analysis.
AB  - Speakers and writers often use metaphor to describe someone or something in a
      referential fashion (e.g., The creampuff didn't show up for the fight to refer to
      a cowardly boxer). Research has demonstrated that readers do not comprehend
      metaphoric reference as easily as they do literal reference (Gibbs, 1990; Onishi
      & Murphy, 1993). In two experiments, we used a naming version of the cross-modal
      lexical priming (CMLP) paradigm to monitor the time-course of comprehending
      spoken metaphoric reference. In Experiment 1, listeners responded to visual probe
      words of either a figurative or literal nature that were presented at offset or
      1000 ms after a critical prime word. Significant facilitatory priming was
      observed at prime offset to probes consistent with the metaphorical
      interpretation of the figuratively referring description, yet no priming was
      found for either probe type at the downstream location. In Experiment 2, we
      partially replicated Experiment 1 results at prime offset and found no priming at
      a probe point placed 1000 ms upstream from prime onset. Taken together, the data
      from these two experiments indicate that listeners are able to comprehend
      metaphoric reference faster than literal reference. Moreover, the effect appears
      to be strongest at prime offset, suggesting that activation of the nonliteral
      interpretation is closely tied to the relationship between the figuratively
      referring description and the intended referent. Implications for theories of
      metaphor comprehension, as well as for research in spoken metaphor, are
      discussed.

PMID- 11975149
TI  - Single-use versus mixed-use learning of transformations: evidence for conceptual
      integration.
AB  - The principle of use-specificity proposes that "compiled" knowledge encapsulates
      the knowledge use in the acquisition context. The efficiency of knowledge use
      should be a monotone function of use-specific practice. Transfer between
      different uses of function concepts should decrease with increasing practice. In
      contrast, the hypothesis of conceptual integration proposes that conceptually
      integrated knowledge can be used flexibly. The efficiency of knowledge use should
      be a monotone function of concept-specific practice. The probability to integrate
      a feature is assumed to depend on its relevance within the acquisition context.
      Transfer between different uses of function concepts should increase with
      increasing practice. In Experiment 1, the effects of practicing a single versus
      two different uses of symbolic functions on learning and subsequent transfer were
      investigated at 1 day and 2 consecutive days of practice. In Experiment 2, these
      effects were investigated for 4 days of practice. The findings support the
      hypothesis of conceptual integration. Performance was mainly a function of
      concept-specific training. Limited usability of acquired knowledge was rare and
      disappeared completely at higher levels of practice.

PMID- 11975151
TI  - The malleability of anchoring effects.
AB  - Anchoring effects--the assimilation of a numeric estimate to a previously
      considered standard--are typically described as very robust and persistent. Based
      on the assumption that judgmental anchoring involves a hypothesis-testing process
      in which judges actively seek and generate judgment-relevant target knowledge, it
      was assumed that anchoring effects might at the same time be fairly malleable.
      Specifically, subtle influences that change the nature of the tested hypothesis
      are likely to affect the magnitude of anchoring. Using a procedural priming task,
      judges were induced to focus on similarities versus differences during a series
      of anchoring tasks. The results demonstrate that the magnitude of the obtained
      effect critically depended on this manipulation. In particular, a more pronounced
      anchoring assimilation effect resulted for judges with a similarity rather than a
      difference focus. Implications of these findings for models of anchoring as well
      as for the nature of the anchoring phenomenon are discussed.

PMID- 11975150
TI  - Nociceptive sensitivity and control: hypo- and hyperalgesia under two different
      modes of coping.
AB  - Effects of perceived control on nociceptive sensitivity were investigated in an
      experimental arrangement with N = 40 healthy volunteers in which the duration of
      painful pressure stimuli was made contingent on success in a tracking task.
      Perceived control over the pain duration was manipulated through varying the
      frequency of success in the tracking task. The amount of painful stimulation
      applied in the high and low control conditions was balanced by a yoked-control
      design. Pain sensitivity was measured before and after the tracking task by means
      of a thermal sensory analyzer. Pain sensitivity was found to decrease in the low
      control condition (hypoalgesia), and to increase slightly in the high control
      condition (hyperalgesia). These effects are explained with reference to a dual
      process model of coping.

PMID- 11975152
TI  - Intimacy, concreteness, and the "self-reference effect".
AB  - Reference to oneself during incidental learning of words frequently results in
      better recall performance than reference to other persons. However, this effect
      occurs under different conditions with differing strength, and sometimes it is
      even reversed. Meta-analyses and further experimental studies suggest that
      increased recall performance under a self-referential encoding task occurs only
      if it is compared with a nonintimate other person and if abstract material is
      presented, irrespective of the type of previously presented words (adjectives or
      nouns). In the current paper, two experiments are reported which support the
      assumption that this intimacy effect on memory only occurs if no pictorial or
      concrete features of the material (nouns) to be learned can be exploited for an
      improvement in encoding or remembering the material. All results agree with
      predicted effect sizes, which were drawn from a meta-analysis and subsequently
      conducted experimental studies. This suggests that a recall advantage of
      referring to oneself compared to other persons is subordinate to the effects of
      concreteness or imageability. Moreover, the current results offer a theoretical
      explanation of some previously reported but nevertheless puzzling results from
      imagery instructions, which indicate decreased recall performance for self
      reference compared to other-reference.

PMID- 11975153
TI  - Helping hands.

PMID- 11975154
TI  - Finders keepers.

PMID- 11975155
TI  - Breaking the silence. Interview by Steven Black.

PMID- 11975156
TI  - Pint please ... and a blood test.

PMID- 11975157
TI  - Breath of life.

PMID- 11975158
TI  - Manager by another name.

PMID- 11975159
TI  - Paint effects.

PMID- 11975161
TI  - Physical child abuse.

PMID- 11975162
TI  - Nursing and medication education.
AB  - AIM: This study set out to explore nurses' current contribution to medication
      education and the clinical contextual factors that influence current practice.
      METHOD: Nurses' practice was investigated using a case study approach. Methods
      used to collect data were: audio-recordings and observation of nurse-patient
      interactions about medication, post-interaction interviews with nurses and
      patients, analysis of relevant written documentation and researcher observation
      and field notes. RESULTS: Findings indicate that nurses' contribution to
      medication education is commonly limited to giving simple information about
      medicines, involving the name, purpose, colour, number of tablets and the time
      and frequency for their administration. CONCLUSION: Nurse-patient relationships,
      patterns of contact and philosophy of care were all identified as contributory
      factors to enabling the practice of medication education in clinical areas.

PMID- 11975163
TI  - Practice development in cancer care: self-help for men with testicular cancer.
AB  - This article describes a joint initiative between health professionals and men
      who had had testicular cancer to set up a self-help group. The aims of this group
      were, and still are, to provide information and support and to instigate
      professional education.

PMID- 11975164
TI  - Childhood diabetes: dietary aspects.
AB  - Insulin-dependent diabetes mellitus in children requires a delicate balance
      between injected insulin and food intake, taking into account physical activity
      and growth.

PMID- 11975166
TI  - Treating the stigma.

PMID- 11975167
TI  - Selecting the right compounds for screening: use of surface-area parameters.
AB  - Polar surface area, total surface area and percentage surface area have been
      calculated from three-dimensional structures of 88 post-emergence herbicides, 93
      pre-emergence herbicides and 237 insecticides. Preferred ranges of values of
      these parameters were identified. Since the compounds in the training sets are
      used on a wide variety of species and target sites with various application
      modes, the parameter ranges are necessarily broad. The utility of the surface
      area parameter ranges in selection of compounds for agrochemical screening was
      compared with the use of ranges of the Lipinski Rule of 5 parameters: molecular
      mass, calculated log P, number of hydrogen-bond donors and number of hydrogen
      bond acceptors. The more computationally intensive surface-area parameters did
      not offer any obvious advantage over the Lipinski Rule of 5 parameters.

PMID- 11975169
TI  - Insecticidal 2-hydroxy-3-alkyl-1,4-naphthoquinones: correlation of inhibition of
      ubiquinol cytochrome c oxidoreductase (complex III) with insecticidal activity.
AB  - The insecticidal and in vitro activities of four homologous series of 2-hydroxy
      and acetoxy-3-substituted-1,4-naphthoquinones have been measured and correlated
      with their (Log) octanol/water partition coefficients (Log Ko/w). In vitro
      activity against mitochondrial complex III was only exhibited by 2-hydroxy-3
      alkyl-1,4-naphthoquinones, indicating that the 2-acetoxy compounds act as
      proinsecticides. Good correlation was observed between in vivo activity against
      the two-spotted spider mite, Tetranychus urticae and inhibition of complex III
      isolated from blowfly flight muscle. Both hydroxy and acetoxy analogues of
      individual compounds exhibited similar levels of in vivo activity with optimum
      activity for analogues with Log Ko/w values of 7-8. In contrast, the acetoxy
      derivatives showed superior in vivo activity against the tobacco whitefly,
      Bemisia tabaci. Complex III isolated from whitefly was optimally inhibited by
      hydroxy analogues with lower Log Ko/w values (6.0-6.5) and was also more
      sensitive than the blowfly enzyme to all the compounds tested.

PMID- 11975168
TI  - Herbicidal action of 2-hydroxy-3-alkyl-1,4-naphthoquinones.
AB  - The main mode of herbicidal activity of 2-hydroxy-3-alkyl-1,4-naphthoquinones is
      shown to be inhibition of photosystem II (PSII). The herbicidal and in vitro
      activities have been measured and correlated with their (Log)octanol/water
      partition coefficients (Log Ko/w). The length of the 3-n-alkyl substituent for
      optimal activity differed between herbicidal and in vitro activity. The maximum
      in vitro activity was given by the nonyl to dodecyl homologues (Log Ko/w between
      6.54 and 8.12), whereas herbicidal activity peaked with the n-hexyl compound (Log
      Ko/w = 4.95). The effect of chain branching was also investigated using isomeric
      pentyl analogues substituted at position 3. All exhibited similar levels of in
      vitro activities but herbicidal activities differed, albeit moderately, with the
      exception of one analogue that was much less phytotoxic. Other modes of action
      were also investigated using two representative compounds. They did not show any
      activity on photosystem I or mitochondrial complex I, or generate toxic oxygen
      radicals by redox cycling reactions. Only moderate activity was found against
      mitochondrial complex III from plants, in contrast to much higher corresponding
      activity using an insect enzyme.

PMID- 11975170
TI  - Quantitative PCR monitoring of the effect of azoxystrobin treatments on
      Mycosphaerella graminicola epidemics in the field.
AB  - Quantitative PCR and visual monitoring of Mycosphaerella graminicola epidemics
      were performed to investigate the effect of curative and preventative
      applications of azoxystrobin in wheat field crops. A non-systemic protectant and
      a systemic curative fungicide, chlorothalonil and epoxiconazole, respectively,
      were used as references. PCR diagnosis detected leaf infection by M graminicola 3
      weeks before symptom appearance, thereby allowing a clear distinction between
      curative and preventative treatments. When applied 1 week after the beginning of
      infection, azoxystrobin curative activity was intermediate between chlorothalonil
      (low effect) and epoxiconazole. When applied preventatively, none of the
      fungicides completely prevented leaf infection. There was some indication that
      azoxystrobin preventative treatments may delay fungal DNA increase more than
      epoxiconazole at the beginning of leaf infection. Both curative and preventative
      treatments increased the time lapse between the earliest PCR detection and the
      measurement of a 10% necrotic leaf area. Azoxystrobin only slightly decreased the
      speed of necrotic area increase compared with epoxiconazole. Hence, azoxystrobin
      activity toward M graminicola mainly resides in lengthening the time lapse
      between the earliest PCR detection and the measurement of a 10% necrotic leaf
      area. Information generated in this way is useful for optimal positioning of
      azoxystrobin treatments on M graminicola.

PMID- 11975171
TI  - Toxicity of biorational insecticides: activity against the green peach aphid,
      Myzus persicae (Sulzer).
AB  - The relationship between dose for each of four biorational insecticides
      (pyrethrins, neem extract, capsiacin extract, insecticidal soap) and mortality of
      the green peach aphid (Myzus persicae) was determined using a laboratory
      bioassay. These insecticides were toxic to aphids and paired mixtures of the
      insecticides provided synergistic activity as measured by aphid mortality under
      the laboratory bioassay conditions. Capsiacin extracts were found to provide low
      levels of mortality alone but acted synergistically in mixtures with the other
      insecticides and provided higher than expected levels of mortality. Activity as
      determined in the laboratory for each insecticide was not evident under field-use
      conditions in five separate experiments. Under field conditions and using common
      application methods, these insecticides did not provide significant levels of
      control of aphids.

PMID- 11975172
TI  - Sensitivity of Venturia inaequalis to trifloxystrobin.
AB  - The sensitivity of Venturia inaequalis to trifloxystrobin was monitored by both
      in vitro (spore germination) and in vivo tests (on apple seedlings). There was
      good correlation between the in vitro and in vivo results. Baseline sensitivity
      was established with 95 bulk isolates from Europe between 1995 and 1998 which
      showed a narrow sensitivity range-factor of up to 17 between the least and most
      sensitive isolates. Monitoring of populations originating from trifloxystrobin
      treated and untreated orchards between 1995 and 1999 showed only sensitive
      isolates and no performance deficiencies were reported. Data also show that
      trifloxystrobin is not cross-resistant to anilinopyrimidines and triazoles, but
      is cross-resistant to kresoxim-methyl, another strobilurin which also inhibits
      the cytochrome bc1 enzyme complex at the Qo-site in the respiration chain of
      fungal mitochondria (QoI inhibitors). Under experimental conditions from a
      specific trial site in Switzerland, where trifloxystrobin has been tested since
      1994, isolates containing conidia resistant to Qo inhibitors were detected in
      1997 and 1999. However no obvious performance deficiencies were reported.
      Nevertheless these results demonstrate a risk for the development of practical
      resistance in V inaequalis to Qo inhibitors and therefore a need to apply
      resistance management principles strictly.

PMID- 11975173
TI  - The effects of phytochemical pesticides on the growth of cultured invertebrate
      and vertebrate cells.
AB  - A range of cultured cells of invertebrate and vertebrate origin was grown in the
      presence of a number of phytochemical pesticides to test the effect of the latter
      on cell proliferation. The main observation was that azadirachtin was a potent
      inhibitor of insect cell replication, with an EC50 of 1.5 x 10(10) M against
      Spodoptera cells and of 6.3 x 10(9) M against Aedes albopictus cells, whilst
      affecting mammalian cells only at high concentrations (> 10(-4) M). As expected,
      the other phytochemical pesticides, except for rotenone, had little effect on the
      growth of the cultured cells. Rotenone was highly effective in inhibiting the
      growth of insect cells (EC50:10(-8) M) but slightly less toxic towards mammalian
      cells (EC50:2 x 10(-7) M). Neem terpenoids other than azadirachtin and those very
      similar in structure significantly inhibited growth of the cell cultures, but to
      a lesser degree. The major neem seed terpenoids, nimbin and salannin, for
      example, inhibited insect cell growth by 23% and 15%, respectively.

PMID- 11975174
TI  - The response of phosphine-resistant lesser grain borer Rhyzopertha dominica and
      rice weevil Sitophilus oryzae in mixed-age cultures to varying concentrations of
      phosphine.
AB  - The response of Rhyzopertha dominica and Sitophilus oryzae (both phosphine
      resistant) in mixed-age cultures to phosphine at fixed concentration-time
      products (CT) of 10,500 to 168,000 microliters litre 1 h (ppm h) with either
      constant, rising or falling concentrations for 7 days was studied at 27 (+/- 2)
      degrees C. At lower CT products, rising concentrations of phosphine led to
      significantly fewer survivors of R dominica and S oryzae. Conversely, exposure to
      falling concentrations of phosphine resulted in significantly more survivors. The
      influence of changing concentrations of phosphine was more pronounced in S oryzae
      than in R dominica. In the latter, at the lower CT products of 21,000 and 42,000
      microliters-1 h, the adult stage proved to be most tolerant, contrary to the
      accepted belief that the egg or pupal stage are always more tolerant to
      phosphine. The results indicate that application of phosphine in rising
      concentrations is more effective than in constant or falling concentrations.

PMID- 11975175
TI  - A protocol for evaluation of the role of disinfectants in limiting pathogens and
      weed moulds in commercial mushroom production.
AB  - In vitro and in vivo evaluations of the effects of three commercial disinfectants
      on isolates of Trichoderma harzianum Rifai and Cladobotryum dendroides (Bull) W
      Gams & Hoozemans were combined in the development of methodologies for realistic
      assessment of disinfectant performance. 'Environ' and 'Purogene' incorporated
      into agar media at 50 mg AI litre-1 were effective in totally preventing the
      mycelial growth of T harzianum and C dendroides isolates, whereas with 'Sudol' a
      concentration of 500 mg AI litre-1 was required. Evaluation of a model in vivo
      system was combined with observations on the fungicidal effects of disinfectants.
      Spore suspensions of T harzianum (Th1), T harzianum (Th2) and C dendroides
      prepared from culture washings with sterilised distilled water were used as
      contaminating inoculum. Environ, Sudol and Purogene in aqueous solutions at 1000
      mg AI litre-1 were sprayed onto these building structure surfaces before or after
      artificial contamination with spore suspensions. Re-isolation from surfaces was
      carried out using agar swabs, which were prepared in visking tubing, applied to
      treated surfaces and incubated at 25 degrees C for 24, 48, 72 or 96 h. Environ
      and Purogene were more effective than Sudol in limiting the recovery of
      Trichoderma spp and C dendroides. All three disinfectants applied 12 h after
      artificial contamination onto wood, concrete or glazed surfaces were able to
      reduce the recovery of these isolates more effectively than when they were
      applied 12 h before artificial contamination. Greater persistence of
      contamination was noted on the rougher surfaces (wood and concrete) than on the
      smoother glazed surface. It was concluded in this in vivo evaluation that, in
      many cases, the protection achieved by the physical nature of the smooth glazed
      tile surfaces was equivalent to that available from the application of
      disinfectants, thus highlighting the attention needed to the nature of building
      surfaces in the structures used in the mushroom industry. The artificial
      contamination and re-isolation techniques allowed significant comparison between
      disinfectant materials, timings and surface types. In the in vivo experiments
      using a single standardised test concentration, the relative fungicidal effects
      of the disinfectants, which varied in the complexity of their active ingredients,
      were better discriminated than the effects observed in vitro, although the
      general trend was similar.

PMID- 11975176
TI  - Chemical alternatives to methyl bromide for the control of root-knot nematodes in
      greenhouses.
AB  - The complete phase-out of methyl bromide from use in developed countries by 1
      January 2005 will cause many problems in agricultural industries that are now
      heavily reliant on its use. Three field experiments were established to compare
      management tactics on tomato and cucumber in commercial greenhouses naturally
      infested with root-knot nematodes (Meloidogyne spp). Reduction of nematode
      juveniles in soil and roots to nil detection levels was observed in all plots
      following soil fumigation with methyl bromide. A significant reduction of
      nematode juveniles and root-galling index was observed in plots treated with
      metham-sodium, dazomet and 1,3-dichloropropene compared with the control and
      plots treated with non-fumigant nematicides. Reduction of the nematode population
      led to an increase in fruit yield. However, data collected from the second
      cultivation season indicated that single control methods such as fumigant or
      contact nematicides alone cannot drastically decrease initial nematode population
      and those nematodes which escape control lead to population increase by the end
      of the cropping season.

PMID- 11975177
TI  - Potential of a novel antibiotic, 2-methylheptyl isonicotinate, as a biocontrol
      agent against fusarial wilt of crucifers.
AB  - Screening for newer bioactive compounds from microbial metabolites resulted in
      the isolation of a novel antibiotic from the culture filtrate, Streptomyces sp
      201, of a soil. The bioactive compound, with antifungal and antibacterial
      activity, was identified as 2-methylheptyl isonicotinate. The antifungal activity
      of live culture, culture broth and the isolated bioactive compound showed marked
      inhibition against dominant soil-borne phytopathogens such as Fusarium oxysporum
      Schlect, F moniliforme Sheldon, F semitectum Berkeley & Ravenel, F solani
      (Martius) Sacc and Rhizoctonia solani Kuehn. The compound had no effect on seed
      germination and seedling development as displayed by root and stem growth of the
      test plant species. In pot experiments with seedlings of cruciferous plants such
      as Raphanus sativus L (radish), Brassica campestris L (yellow mustard), Brassica
      oleracea var botrytis L (cauliflower), the antibiotic compound showed promising
      protective activity of 92% when seeds of the test plants were treated at a dose
      of 50 micrograms ml-1 prior to sowing. Seed treatment with a spore suspension (3
      x 10(8) spores ml-1) of the Streptomyces sp 201 displayed protective activity in
      the range of 56-60%. Seeds coated with 2.5% methyl cellulose-amended spores of
      the antagonist showed protective activity in the range of 64-72%. Further, seed
      treatment with the culture filtrate of the antagonist also showed promising
      protective activity in the range of 64-84%.

PMID- 11975178
TI  - Effect of cropping cycles and repeated herbicide applications on the degradation
      of diclofop-methyl, bentazone, diuron, isoproturon and pendimethalin in soil.
AB  - A greenhouse study was conducted to investigate the ability of four crops (wheat,
      corn, oilseed rape and soybean) to influence the degradation of bentazone,
      diclofop-methyl, diuron, isoproturon and pendimethalin in soil. The present study
      showed that microbial biomass-carbon was significantly higher in planted soils
      than in bulk soil, especially with wheat and corn, after several cropping cycles.
      The biomass in corn and soybean planted soils was adversely affected by bentazone
      but recovered after three cropping cycles. In wheat-planted soils, diclofop
      methyl application resulted in persistent increase of the amount of microbial
      biomass. Bentazone did not show accelerated degradation even after five
      successive treatments, differing from diclofop-methyl, for which two applications
      were sufficient to enhance significantly its rate of degradation. Enhanced
      degradation of diclofop-methyl was even more pronounced in wheat-planted soil.
      The rates of mineralisation of diuron, isoproturon and pendimethalin were not
      affected after the first cropping cycle, but were significantly increased in
      planted soils after five cropping cycles. The results confirm that plants may
      promote pesticide degradation in soil by stimulating biodegradation processes. In
      the case of diclofop-methyl, stimulation of accelerated degradation was observed.

PMID- 11975179
TI  - Stimulating effects of the insecticide chlorpyrifos on host searching and
      infestation efficacy of a parasitoid wasp.
AB  - Hymenopterous parasitoids play an important role in the control of insect
      populations. During oviposition, Hymenopterous parasitoids use cues such as
      odours from their environment to locate their specific host. Leptopilina
      heterotoma (parasitoid of Drosophila larvae) locate their host by probing the
      substrate with the ovipositor. This behaviour can be induced by the odour of the
      host substrate alone. We analysed the sub-lethal effects of chlorpyrifos at LD20
      on the probing activity in response to a fruit odour (banana). The insecticide
      increased the percentage of females spontaneously probing in response to the
      odour. Parasitoid females were then conditioned to associate banana odour with
      the oviposition in host larvae. This conditioning enables parasitoids to memorize
      the odour and to increase their probing response to this odour. During the
      olfactory conditioning, females exposed to the insecticide found and oviposited
      in host larvae more quickly than control females. One hour after the olfactory
      conditioning, females exposed to the insecticide presented a higher increase of
      their probing response to the odour than controls. Twenty-four hours after
      conditioning, the stimulation produced by chlorpyrifos was no longer perceptible,
      but the level of response of conditioned females was still higher than that of
      non-conditioned females, showing that odour memory was not impaired by the
      insecticide treatment. These sub-lethal effects, that stimulate host searching by
      parasitoids without impairing odour memorization, could increase their parasitic
      efficiency.

PMID- 11975180
TI  - Evidence for oil-induced oxidative stress to larvae of the lightbrown apple moth,
      Epiphyas postvittana Walker (Lepidoptera: Tortricidae).
AB  - For the purpose of understanding better the mode of action of alkanes on insects,
      the relationship between mortality, weight loss in oxygen enriched atmospheres
      and dietary antioxidants was examined using an alkane, C15 Ampol CPD and a spray
      oil, C23 DC-Tron NR, on lightbrown apple moth, Epiphyas postvittana Walker,
      (LBAM). The results showed that the surfactant blend used in CPD was an
      insignificant contributor to the overall toxicity of dilute oil/water emulsions.
      Higher weight loss occurred in CPD-dipped larvae than C23 DC-Tron NR-dipped
      larvae, which suggests that alkanes disrupt tracheal waxes and render insects
      more prone to desiccation. High levels of oxygen increased the toxicity of CPD to
      LBAM larvae. In addition, dietary supplements of anti-oxidant, alpha-tocopherol,
      fed to LBAM larvae were successful in reducing the toxicity of CPD. These results
      suggest that the alkane may contribute to oxidative injury. The potential role of
      oil-induced oxidative stress in acute and chronic toxicity in insects is
      discussed.

PMID- 11975181
TI  - Environmental fate of metalaxyl and chlorothalonil applied to a bentgrass putting
      green under southern California climatic conditions.
AB  - Putting greens usually receive high inputs of fertilizers and pesticides to meet
      the high demand for visual quality and to overcome the stress from close mowing
      and traffic. In this study, two commonly used fungicides, metalaxyl (methyl N
      (methoxyacetyl)-N-(2,6-xylyl)-DL-alaninate) and chlorothalonil (2,4,5,6
      tetrachloro-1,3-benzenedicarbonitrile), were evaluated for their partitioning and
      persistence in a bentgrass (Agrostis palustris Huds) putting green under southern
      California climatic conditions. The putting green site was constructed according
      to the US Golf Association (USGA) specifications. Lysimeter assemblies installed
      at the center of each plot were used to monitor the leachate, flux chambers were
      used to measure volatilization, clippings were collected to determine the
      residues on grass, and soil cores were sampled to determine residues in the soil
      profile. Results showed that cumulative volatilization loss accounted for 0.10
      and 0.02%, clipping removal 0.11 and 0.13%, and cumulative leaching 0.71 and
      0.002% of the applied metalaxyl and chlorothalonil, respectively. The two
      fungicides were mainly found in the top 10 cm of the soil profile due to the high
      organic carbon content in the thatch and mat layers. The dissipation half-life
      was 1.4 days for metalaxyl and 4.9 days for chlorothalonil on grass, shorter than
      those found in agricultural fields. This study showed that, under normal turf
      management practices, the offsite transport of the parent fungicides was minimal.
      Future research should focus on investigating the fate and mobility of the
      metabolites of the fungicides.

PMID- 11975182
TI  - A mechanistic analysis of penetration of glyphosate salts across astomatous
      cuticular membranes.
AB  - Penetration of glyphosate salts across isolated poplar (Populus canescens (Aiton)
      Sm) cuticular membranes (CM) was studied using Na+, K+, NH4+, trimethylsulfonium+
      (TMS) and isopropylamine+ (IPA) as cations. After droplet drying, humidity over
      the salt residues on the outer surfaces of the CM was kept constant, and
      cuticular penetration was monitored by sampling the receiver solution facing the
      inner surfaces of the CM. Glyphosate salts disappeared exponentially with time
      from the surfaces of the CM. This first-order process could be quantitatively
      described using rate constants (k) or half-times (time for 50% penetration;
      t1/2). Humidity strongly affected the velocity of penetration, as k increased by
      factors of 5.3 (K-glyphosate), 6.9 (TMS-glyphosate), 7.1 (NH4-glyphosate), 8.5
      (Na-glyphosate) and 10.5 (IPA-glyphosate) when humidity was increased from 70 to
      100%. Depending on the type of cation and humidity, t1/2 varied between 4 and
      70h, but the humidity effect was statistically significant only at 100% humidity,
      when half-times were highest with IPA-glyphosate and lowest with TMS-glyphosate.
      Glyphosate acid penetration was measured only at 90% humidity and found to be
      extremely slow (t1/2 = 866 h). Adding 0.2 g litre-1 of a wetter
      (alkylpolyglucoside) to the donor increased IPA-glyphosate rate constants by
      about four times, but increasing concentration produced no further increase in k.
      When donors contained 0.2 g litre-1 wetter, further additions of 4 g litre-1
      Ethomeen T25 did not change rate constants measured with IPA-glyphosate at 90%
      humidity, while Genapol C-100 and diethyl suberate increased k by only 35%.
      Concentration of IPA-glyphosate (1, 2 and 4 g litre-1) did not influence k at 90%
      humidity, and pH of donor solutions (4.0, 7.7, 9.5) had no effect on k of K
      glyphosate at 90% humidity. Temperature (10 to 25 degrees C) had only a small
      influence on velocity of penetration of IPA-glyphosate and K-glyphosate, as
      energies of activation amounted to only 4.26 and 2.92 kJ mole-1, respectively.
      These results are interpreted as evidence for penetration of glyphosate salts in
      aqueous pores.

PMID- 11975183
TI  - Adsorption-desorption studies of alachlor, metolachlor, EPTC, chlorothalonil and
      pirimiphos-methyl in contrasting soils.
AB  - Five soils with different organic matter contents ranging from 0.48 to 10.4% were
      used to study the adsorption and desorption of alachlor, metolachor, EPTC,
      chlorothalonil and pirimiphos-methyl in batch experiments. The isotherm shapes
      according to Giles classification were S-type for alachlor, metolachlor and
      chlorothalonil, changing to L-type for the latter as the level of soil organic
      matter increased, and L-type for EPTC and pirimiphos-methyl. The adsorption
      isotherms fitted the Freundlich equation x/m = KfCe1/n. The Kf values increased
      with the increase of organic matter content. The amounts of pesticides adsorbed
      over a range of concentrations of 0.1-20 mg litre-1 reached 63.1% for alachlor,
      69.2% for metolachlor, 89.3% for EPTC, 98.4% for chlorothalonil and 96.3% for
      pirimiphos-methyl. The increase of the amounts desorbed with acetone indicated
      that the sorption of organic compounds onto organic matter occurred principally
      via weak London-type induction forces, or dispersion forces which are
      characteristics of the physical adsorption process.

PMID- 11975184
TI  - Prediction of pesticide concentrations found in rivers in the UK.
AB  - SWATCATCH is a distributed model combined with databases within a GIS as the
      POPPIE system to predict pesticide concentrations in rivers at the catchment
      outlet. The model was evaluated against a dataset of pesticide concentrations in
      rivers of England and Wales. More than 2000 individual analyses in each of the
      years 1995 and 1997 covered approximately 150 catchment-pesticide combinations
      drawn from 29 catchments and 16 pesticides, themselves selected to represent a
      range of characteristics and properties. SWATCATCH was better able to simulate
      maximum pesticide concentrations at any time during the year than the proportion
      of samples containing residues of a particular pesticide above the limit of
      quantification. The model simulated maximum pesticide concentrations in surface
      waters which were within a factor of 10 of those observed for 66-74% of catchment
      pesticide-year combinations. Simulated and observed frequency of detection could
      not be differentiated using a Chi 2 test for 54-67% of simulations. Time series
      analysis for seven of the 29 catchment-pesticide combinations indicated that
      measured and detected series of concentrations generally followed similar
      patterns. The evaluation supports the intended use of the model in assisting the
      construction of pesticide monitoring programmes.

PMID- 11975185
TI  - Effect of surface material on electrostatic charging of houseflies (Musca
      domestica L).
AB  - Houseflies (Musca domestica L) accumulated electrostatic charges when walking
      over clean, uncharged dielectric surfaces. The charges elicited on a walking
      housefly by a range of materials were quantified, allowing a triboelectric series
      to be determined relative to M domestica. This ranged from surfaces that charged
      individuals positively, e.g. Correx (corrugated polypropylene) [.1 (+/- 4.2)pC],
      to those that applied a negative charge, e.g. clear cast acrylic [-14.9 (+/-
      2.9)pC]. Maximum positive and negative charges accumulated by individual M
      domestica were +73 and -27 pC. Replicate measurements on the same fly and surface
      showed little variation. Variation between individuals was not related to sex and
      was not consistent between surfaces. Different materials charged M domestica
      significantly differently and individual flies had significantly different
      charging properties. Variation in temperature between 21.3 degrees C and 24.7
      degrees C and humidity between 24% and 41% RH significantly affected charge
      accumulated by M domestica on some surfaces, although further experimentation is
      needed to confirm this. The implications of this work are discussed in relation
      to insect trap design and pollination biology.

PMID- 11975186
TI  - Dye injection for predicting pesticide movement in micro-irrigated polyethylene
      film mulch beds.
AB  - A new method is described for tracing water movement in polyethylene film covered
      soil beds. Dye was delivered via a drip tape micro-irrigation system which was
      placed in the bed as the soil beds were shaped and covered with polyethylene
      film. The dye was injected into the system and irrigated with water for 4-24 h at
      0.41-1.38 bar (41-138 kPa) pressure depending on the experiment. The dye appeared
      as blue circles on the soil surface within 20 min of injection and produced a
      three-dimensional pattern in the soil profile. Injection-irrigation-pressure
      scenarios were evaluated by measuring dye movement directly below and between
      emitters by sliding fabricated blades vertically into the bed at the desired
      examination point and excavating the soil away from the blade. The dye typically
      produced a U shape on the face of the bed and the area was calculated for each of
      these exposed faces. The area increased as the length of irrigation and water
      pressure increased. Interrupted irrigation (pulsing) scenarios did not alter the
      calculated areas encompassed by the dye compared to uninterrupted irrigation
      scenarios. The blue dye provided a direct, inexpensive and easy method of
      visualizing water movement in soil beds. This information will be used to
      optimize application of emulsifiable plant-care products in polyethylene film
      mulch beds.

PMID- 11975187
TI  - An index technique to monitor broadcast calibration and bait pick up, plus rodent
      and avian sign under arid conditions.
AB  - As part of product-performance and wildlife-hazards studies of 2% zinc phosphide
      (Zn3P2) steam-rolled-oat baits (11.2 kg ha-1) to reduce vole populations
      (Microtus spp) in alfalfa (Medicago sativa), we used randomly located, brushed
      dirt plots (eight approximately 930-cm2 plots per 0.2-ha enclosure) to monitor
      bait-broadcast and -removal patterns, as well as to index vole and avian sign.
      Research was conducted in 18 x 0.2-ha enclosures containing 2.5-year-old stands
      of alfalfa; a 2-day pre-bait (placebo baits broadcast in all enclosures) period
      followed by a 14-day test-bait period (placebo and 2% Zn3P2 baits in nine
      enclosures each) characterized the bait exposures. Baits were broadcast manually
      by two certified pesticide applicators (CPAs) using Spyker Model-75 spreaders.
      Baits that fell onto plots were counted < 30 min later to assess the uniformity
      of bait distribution. The main statistical design was a 2 (placebo or Zn3P2
      baits) x 3 (vole-only, vole-pheasant, vole-quail exposures) x 14 (days)
      factorial, with days considered repeated measurements. In the six vole-only
      enclosures, baits were removed from the brushed-dirt plots and replaced with four
      0% or 2% Zn3P2 baits (one per 232.6-cm2 quadrant; 32 per enclosure); these
      'placed' baits were then monitored daily for removal, while the surfaces of all
      plots were monitored daily for the presence:absence of animal/bird sign. Key
      results were: (a) 3.51 (+/- 2.66) and 3.39 (+/- 3.52) mean (+/- SD) baits were
      found on plots after pre-bait and test-bait broadcasts, respectively--less than
      the predicted 4.52 particles per 930-cm2 plot; (b) baits 'placed' on plots in
      placebo-baited enclosures were removed earlier than those in Zn3P2-baited
      enclosures--data in agreement with observed vole mortality; and (c) species x
      bait interactions occurred for both the vole- and pheasant-sign counts, but not
      quail-sign counts--data also indirectly confirming Zn3P2-induced mortality
      effects on voles and pheasants. This technique has utility for a variety of
      wildlife biology and chemical registration studies; although limited to arid
      conditions, the technique affords useful indices of broadcast calibration, bait
      pick-up, as well as target and non-target species mortality.

PMID- 11975188
TI  - Synthesis of biotin conjugates of the antifungal compound cymoxanil.
AB  - Biotin conjugates are of considerable value in investigating the mode of action
      of biologically active compounds. Two biotin conjugates related to the antifungal
      compound cymoxanil [1-(2-cyano-2-methoximinoacetyl)-3-ethyl urea] were prepared
      as the first step in an effort to employ display cloning to identify the
      compound's target site. In the first conjugate, prepared in five steps, the
      biotin moiety was attached at the position occupied by the ethyl group in
      cymoxanil. In the second conjugate, prepared in four steps, the biotin moiety was
      attached through the oxime functional group.

PMID- 11975189
TI  - Fate of spinosad in litter and soils of a white spruce plantation in central
      Ontario.
AB  - Spinosad is a natural insecticide with potential as a novel biorational control
      agent for spruce budworm (Choristoneura fumiferana [Clem]), the most destructive
      insect defoliator of spruce and balsam fir in Canada. Concurrent terrestrial fate
      experiments were conducted under full coniferous canopy and in a natural opening
      of a mature white spruce (Piecea glauca [Moench]) plantation of central Ontario
      to examine the fate and persistence of spinosad in the forest floor and
      underlying soils. Mean initial residues of spinosyn A and D were approximately
      0.2 and 0.02 microgram g-1, respectively, in thatch and exposed soils, but were
      substantially higher, 2.72 and 0.36 micrograms g-1, in litter under coniferous
      canopy. Results demonstrated that spinosad residues in spruce litter,
      graminaceous thatch and exposed sandy loam soils dissipated rapidly, following
      hyperbolic or exponential decline models. Dissipation time (DT50) values ranged
      from 2.0 to 7.8 days, depending on matrix and experimental conditions. Transient
      increases in demethylated metabolite residues confirmed that the parent product
      was degraded in situ. No evidence of vertical mobility of any of the analytes was
      observed.

PMID- 11975190
TI  - Herbicide sensitivity of transgenic multiple herbicide-tolerant oilseed rape.
AB  - Glyphosate and glufosinate-ammonium herbicide tolerance traits were combined into
      both winter and spring lines of Brassica napus L. This allowed the study of
      possible interactions between these transgenes in two genetic backgrounds when
      treated with a variety of herbicides. Selective herbicides that are commonly used
      within Brassica crops showed no adverse effects on the transgenic plants or their
      null controls. Lines containing both glyphosate and glufosinate transgenes
      remained tolerant to their respective herbicides, regardless of the presence of
      the second tolerance transgene. Lines containing only a single transgene retained
      tolerance to the encoded trait and did not show cross-tolerance to the second.
      Null lines were killed by either herbicide. All plant lines, regardless of their
      transgene content, were found to be equally susceptible to three herbicides
      (paraquat, metsulfuronmethyl and mecoprop), commonly used to remove volunteer B
      napus from succeeding crops and set-a-side land.

PMID- 11975191
TI  - Accelerating the process of drug discovery.

PMID- 11975192
TI  - In vitro screening of cytochrome P450 induction potential.

PMID- 11975193
TI  - Drug transport across the blood-brain barrier.

PMID- 11975194
TI  - The development and implementation of bioanalytical methods using LC-MS to
      support ADME studies in early drug discovery and candidate selection.

PMID- 11975195
TI  - Strategies in lead selection and optimization: application of a graphical model
      and automated in vitro ADME screening.

PMID- 11975196
TI  - High-throughput screening--brains versus brawn.

PMID- 11975197
TI  - Relation of molecular properties with drug absorption and disposition.

PMID- 11975198
TI  - Modelling human cytochrome P450-substrate interactions.

PMID- 11975199
TI  - The role of pharmacokinetics in drug discovery: finding drug candidates with the
      greatest potential for success.

PMID- 11975200
TI  - Rapid permeability screening in drug discovery to predict human intestinal
      absorption.

PMID- 11975201
TI  - Drug metabolism assays and their use in drug discovery.

PMID- 11975202
TI  - Prediction of human pharmacokinetics based on preclinical in vitro and in vivo
      data.

PMID- 11975203
TI  - Experts in practice.

PMID- 11975204
TI  - On the road with Eric. Interview by Alison Moore.

PMID- 11975206
TI  - Making an impact.

PMID- 11975205
TI  - Claire's reign. Interview by Dina Leifer.

PMID- 11975207
TI  - One foot in the past.

PMID- 11975209
TI  - The role of the clinical nurse specialist.
AB  - AIM: To investigate the current work and role of the clinical nurse specialist.
      METHOD: Twenty semi-structured interviews were undertaken with clinical nurse
      specialists and analysed using the constant comparative approach of grounded
      theory. RESULTS: The clinical nurse specialists (CNSs) in this study identified
      the communicator-carer role as their key remit. This was perceived as being
      extremely effective and unique as well as providing the CNS with his or her main
      source of job satisfaction. Nonetheless, intrinsic desires and external demands
      create a considerable workload that therefore needs to be prioritised. In
      addition, the legitimacy of certain demands needs to be challenged to ensure
      appropriate demands are met and relevant opportunities realised. CONCLUSION: The
      pivotal role of the CNS might be under threat as it fails to fulfill its original
      extensive remit, specifically that of undertaking research.

PMID- 11975210
TI  - Cannabis: its therapeutic use.
AB  - This article provides an overview of the issues surrounding the use of cannabis
      for therapeutic purposes. Examples of some of the ethical issues related to
      professional practice are discussed. The authors do not advocate legalising
      cannabis for all, but the therapeutic advantages and disadvantages of using
      cannabis are highlighted.

PMID- 11975213
TI  - University challenge.

PMID- 11975211
TI  - Management of work-related stress in nursing.
AB  - Evidence suggests that health professionals experience significant levels of
      occupational stress, which can lead to illness, increased absenteeism, high staff
      turnover, unsafe behaviour and increased accident rates. Nia Harris highlights
      strategies to manage and prevent high levels of stress at work.

PMID- 11975216
TI  - The requirements of medical writing.

PMID- 11975217
TI  - Gallbladder management in obesity surgery.
AB  - BACKGROUND: In the 1980s, some surgeons recommended routine cholecystectomy for
      patients undergoing bariatric surgery. This was based on the high prevalence of
      gallstones in the obese and concern that rapid weight loss would increase the
      risk of gallbladder disease. Others recommended waiting for a lower weight and a
      definite need. With increasing prevalence and severity of obesity and increased
      use of gastric reduction surgery for weight control, it seemed appropriate to
      review the current standard of care for cholecystectomy. A survey was also made
      of ursodeoxycholic acid usage for prevention of gallstone formation. METHODS:
      Data collected from active contributors for the 28th Report of the International
      Bariatric Surgery Registry (IBSR) were examined. Two questionnaires were also
      sent to members of the American Society for Bariatric Surgery (ASBS). The first
      (Q1) asked about the indications for cholecystectomy. The second (Q2) asked about
      ursodeoxycholic acid usage for prevention of gallstone formation during rapid
      weight loss following surgical treatment of obesity. RESULTS: There has been an
      increase in concurrent cholecystectomy during the last 15 years. Some of this is
      due to a shift from simple gastric restrictive operations to gastric bypass with
      gastric restriction. When the most extensive bypass of intestine is used, as in
      distal Roux-en-Y gastric bypass (RYGBP-X) or biliopancreatic diversion with a
      duodenal switch (BPD-DS), all patients were reported to have undergone
      cholecystectomy. Only 30% of surgeons performing standard Roux-en-Y gastric
      bypass (RYGBP) remove normal-appearing gallbladders. Ursodeoxycholic acid is used
      to prevent gallstone formation in one-third of patients when a normal-appearing
      gallbladder is left in place. CONCLUSIONS: Prophylactic cholecystectomy is left
      to the discretion of the surgeon when RYGBP is used. There has been an increase
      in cholecystectomy and malabsorptive operations during the last 15 years. When
      most of the small bowel is bypassed, all remaining gallbladders are removed. For
      patients with simple restriction operations, normal-appearing gallbladders are
      usually left in place. Urso-deoxycholic acid during rapid weight loss for
      prevention of gallstone formation is used in one-third of patients with remaining
      gallbladders.

PMID- 11975218
TI  - The effect of obesity on neutrophil Fc receptors and adhesion molecules (CD16,
      CD11b, CD62L).
AB  - BACKGROUND: There is a large body of epidemiological data associating obesity
      with a wide variety of clinical disease processes, including cancer and wound
      infections. However, defining the specific defects of neutrophils has proved
      difficult and often contradictory. METHODS: 27 patients having gastric bypass
      surgery for obesity (BMI > 40) were compared with 10 normal controls (BMI < 26).
      Relative neutrophil frequencies and expression of the activation antigens CD11b
      (integrin adhesion molecule), CD16 (Fc receptor), and CD62L (L-selectin), were
      evaluated by flow cytometry. RESULTS: The study control group had a mean age of
      37 +/- 7.6 yrs (range 30 to 57) with no significant health problems. Their mean
      BMI was 23 +/- 2.5 kg/m2 (range 21-26). The mean age of the sample group was
      40.36 +/- 13.7 yrs (range 18 to 60) with a mean BMI of 52 +/- 8.2 kg/m2 (range 41
      to 72). These patients had a large spectrum of diseases that afflict the morbidly
      obese, including hypertension (14), arthritis (10), exertional dyspnea (13),
      venous stasis (7), hypothyroidism (2), NIDDM (3), heart murmur (1), along with 8
      smokers. The neutrophil frequency in the obese patients was comparable to the
      controls (control 49% vs obese 51%). Additionally, there was no apparent
      difference between obese and controls regarding CD11b or CD16 expression (424 vs
      498 gmf) (267 vs 262 gmf). However, there was a significant reduction of CD62L (L
      selectin) expression noted in the morbidly obese with respect to controls (102 vs
      303 gmf, p < 0.001). An increased percentage of eosinophils when compared to
      controls (6.7% vs 1.73%, p < 0.001) was also observed. CONCLUSION: Discordant
      CD11b/CD62L levels, depressed levels of CD62L, and elevated eosinophil
      percentages support the hypothesis that a chronic inflammatory state exists in
      morbid obesity. Decreased levels of CD62L in the morbidly obese neutrophil pool
      possibly affect the neutrophil's ability to activate and migrate to sites of
      inflammation. This may play a role in the higher incidence of infectious
      complications seen in morbidly obese individuals.

PMID- 11975219
TI  - Does reduction in gastric acid secretion in bariatric surgery increase diet
      induced thermogenesis?
AB  - BACKGROUND: Patients who have undergone gastrectomy for benign ulcer do not
      develop obesity. Furthermore, morbidly obese patients who undergo biliopancreatic
      diversion (BPD), Roux-en-Y gastric bypass (RYGBP) and vertical banded
      gastroplasty (VBG) plus truncal vagotomy, may lose more weight compared with
      patients who undergo VBG alone. A common characteristic of the above is the
      reduction of gastric hydrochloric acid secretion. We investigated whether
      reduction in gastric acid increases dietary-induced thermogenesis because of
      maldigestion of foods, and this may account for the greater weight loss in the
      above situations. MATERIALS AND METHODS: 22 volunteers without symptoms from the
      upper gastrointestinal tract were studied. Gastric pH was measured and resting
      energy expenditure (MREE), using indirect calorimetry, was determined before and
      8 hours after consumption of a standard meal. Parameters were measured again
      after 2 months administration of proton pump inhibitors in all volunteers.
      RESULTS: Although significant reduction of gastric acid secretion occurred (p <
      0.01), following administration of proton pump inhibitors, the fasting and
      postprandial MREE remained unchanged (p > 0.05). CONCLUSIONS: The reduction in
      gastric acid secretion does not increase the energy requirements for digestion of
      foods and thus is neither the mechanism responsible for the increased weight loss
      observed after RYGBP or BPD, nor the explanation for the lean appearance of
      gastrectomized patients.

PMID- 11975220
TI  - Laparoscopic standard biliopancreatic diversion: technique and preliminary
      results.
AB  - BACKGROUND: A technique for standard laparoscopic BPD was developed. METHODS:
      Standard laparoscopic BPD was performed in 26 morbidly obese patients with mean
      BMI 43. Details of the technique, using 6 trocars, and instrumentation are
      described. Intestinal limb lengths were measured fully stretched, and the gastric
      remnant volume was also measured. Both enteroenteral and gastrointestinal
      anastomoses were fashioned with a side-to-side technique using the endoGIA, the
      conjoined defect being closed with a manual running seromuscular suture. RESULTS:
      6 and 12 month weight loss results were similar to those obtained in open BPD.
      CONCLUSION: Laparoscopic standard BPD is a feasible alternative to the open
      operative procedure, the major advantage being the likely near total avoidance of
      wound hernia.

PMID- 11975221
TI  - Laparoscopic biliopancreatic diversion with duodenal switch: technique and
      initial experience.
AB  - BACKGROUND: The duodenal Switch (DS) is a variant of the biliopancreatic
      diversion (BPD) for the surgical treatment of morbid obesity. MATERIALS AND
      METHODS: The laparoscopic DS (LapDS) operation is described, and the early
      surgical outcomes of 16 patients are reported. RESULTS: Postoperative stay was 5
      to 8 days. Local wound infection at a trocar site was the most common local
      complication. CONCLUSION: LapDS is an advanced, complex and feasible technique in
      bariatric surgery.

PMID- 11975222
TI  - Analysis of weight loss with the biliopancreatic diversion of Larrad: absolute
      failures or relative successes?
AB  - BACKGROUND: The authors studied whether morbidly obese patients who failed in
      stated weight loss criteria may be considered absolute failures or relative
      successes. METHODS: 75 morbidly obese patients underwent biliopancreatic
      diversion (BPD) of Larrad, with a 4/5 gastrectomy (residual gastric volume 150
      200 ml), a biliopancreatic limb divided 50 cm distal to Treitz' ligament, a 50-cm
      common limb and an alimentary limb of nearly all the bowel length (500-600 cm).
      Every patient had a follow-up of 5 years. A percent excess weight loss (%EWL) <
      50% was considered a "failure". We analyzed the post-surgical changes in the
      preoperative obesity-related problems in these patients and the causes of the
      weight loss failure. RESULTS: At 5 years after the BPD of Larrad, 9 patients
      (12%) had a %EWL < 50%, with a mean %EWL of 36 in these patients. Most of these
      failed patients were cured or improved of their preoperative illnesses. The 2
      males were alcoholics, and 6 of the 7 females had an abnormal psychological
      examination. Comparing the "failed" patients with the successful group, there is
      a statistically significant influence (p < 0.01) of lack of satiety, unmarried
      status, housewife or unemployed. CONCLUSION: Patients judged as a failure by
      weight loss criteria after bariatric surgery should not be considered absolute
      failures, because most of their preoperative illnesses were cured or improved,
      improving their quality of life. Thus, they are "relative successes".

PMID- 11975223
TI  - Outcome evaluation after bariatric surgery.

PMID- 11975224
TI  - Laparoscopic reoperative bariatric surgery: experience from 27 consecutive
      patients.
AB  - BACKGROUND: 10 to 25% of patients undergoing bariatric surgery will require a
      revision, either for unsatisfactory weight loss or for complications. Reoperation
      is associated with a higher morbidity and has traditionally been done in open
      fashion. The purpose of this study was to determine the safety and efficacy of
      reoperative surgery using a laparoscopic approach. METHODS: A retrospective
      review of medical records over a 22-month period was conducted. 27 consecutive
      obesity surgery patients, who had undergone a laparoscopic revision, were
      identified. 26 of the 27 patients were women. The average age was 40.3 years
      (range 20 to 58 years) and average original preoperative body mass index (BMI)
      was 51.6 kg/m2 (range 42 to 66.5). The 27 primary bariatric operations consisted
      of vertical banded gastroplasty (12), gastric band placement (9) and gastric
      bypass (6). 17 of them were open procedures. After the primary surgery, the
      lowest average BMI was 37.6 kg/m2 (range 21 to 52), which increased to 42.7 kg/m2
      (range 29 to 56) before reoperation. 24 of the 27 reoperations were indicated for
      insufficient weight loss. On average, revision was undertaken 52 months after the
      primary procedure (range 12 to 240 months). RESULTS: 24 of the 27 laparoscopic
      reoperations were conversions to a gastric bypass. A second reoperation was
      indicated for insufficient weight loss on four occasions. In one case, conversion
      to open surgery was required. The average operative time was 232 +/- 18.5 minutes
      (range 120 to 480) and length of hospital stay was 3.7 days (range 1 to 9). 22%
      percent of patients (6) experienced complications, including pneumothorax,
      gastric remnant dilation, gastrojejunostomy stenosis, port-site hernia and
      protein malnutrition. There was no mortality in the study. The average BMI was
      35.9 kg/m2 (range 27 to 45.5) 8 months after surgery (range 1 to 22 months).
      Compared with a preoperative BMI of 42.7 kg/m2, the weight loss was statistically
      significant (p < 0.001). CONCLUSION: Our results compare favorably with those
      reported for open reoperative bariatric surgery. A laparoscopic approach may be
      considered a feasible and safe alternative to an open operation.

PMID- 11975225
TI  - Outcome of gastric bypass patients.
AB  - BACKGROUND: The authors analyzed previously studied outcomes of Roux-en-Y gastric
      bypass (RYGBP), examined pre-surgical factors of post-surgical outcomes, and
      examined some of the psychosocial benefits. METHODS: A retrospective chart review
      was conducted of 138 patients who underwent RYGBP between 1997 and 2000. Pre
      surgical BMI, cholesterol, blood pressure, creatinine, number of
      antidepressant/glycemic drugs, and hemoglobin were recorded. Post-surgical follow
      up was reviewed to examine changes. RESULTS: Statistically significant changes
      were found in BMI, hypertension, cholesterol and glycemic control. Surgery was
      found to reduce creatinine from a pre-surgery average of 1.14 to 1.01 (n = 11, p
      = .0015)). Patients with early post-operative complications (defined as length of
      stay > 6 days or re-hospitalization within 1 month following surgery) had an
      average BMI of 57.58 (n = 23) vs a BMI of 49.9 (n = 103) in those who did not
      experience any complications (p = 0.0004). There was a statistically significant
      decrease in the rate of anti-depressant use following surgery. 49 patients were
      on antidepressants before surgery vs 38 following surgery (p = .0016).
      CONCLUSION: RYGBP significantly improves hypertension, hyperlipidemia and type II
      diabetes, and may also improve kidney function. Patients with higher pre-surgical
      BMIs are at greater risk for post-surgical complications. Postoperative
      antidepressant use appears to decrease.

PMID- 11975226
TI  - The effects of Roux-en-Y gastric bypass surgery on body image.
AB  - BACKGROUND: Numerous studies examine the physical effects of Roux-en-Y gastric
      bypass (RYGBP) surgery on morbid obesity. However, the effects of this surgery on
      psychosocial issues such as body image have not been extensively studied.
      METHODS: This pilot study used a cross-sectional design to examine the effects of
      RYGBP surgery on patients' perceived body image. Four groups (n = 20) were
      assessed for perceived change in body image at 4 time intervals. These included
      pre-surgery, 1 to 3 weeks post-surgery, 6-months post-surgery, and 1-year post
      surgery, with two measures of body image. One-way ANOVA was applied, with body
      image measures as the dependent variables, and time since surgery (group) as the
      independent variable. Planned post-hoc t-tests were applied to assess the
      differences between specific groups (pre vs. 1 week, pre vs. 6 months post, 6
      months post vs. 1 year post). RESULTS: Results of the one-way ANOVAs revealed
      significant improvement on perceptions of body image over time following surgery.
      Follow-up t-tests revealed that the most significant improvement occurred between
      pre-surgery and 6 months post-surgery. Although smaller, the change between 6
      months post-surgery and 1 year post-surgery was also significant. CONCLUSION:
      While RYGBP results in numerous medical and physical benefits, this study reveals
      that there are also dramatic improvements in perceived body image, demonstrating
      the impact of this surgery on a patient's psychosocial health.

PMID- 11975227
TI  - Binge eating among gastric bypass patients at long-term follow-up.
AB  - BACKGROUND: A better understanding of the relationship of eating behavior and
      attitudes to weight loss following gastric bypass (GBP) will enable the
      development of interventions to improve outcome. Thus, the present study sought
      to characterize the postoperative weight, eating behavior, and attitudes toward
      body shape and weight in a cross-section of GBP patients. A second objective was
      to examine the relationship of postoperative binge eating to surgery outcome.
      METHODS: 99 patients who underwent GBP > 2 and < 7 years before the study start
      date completed the Eating Disorder Examination-Questionnaire (EDE-Q) and the
      Three-Factor Eating Questionnaire (TFEQ). Subjects self-reported their current
      body weight, weight change over the past 3 months, and lowest weight since
      surgery. RESULTS: BMI remained significantly below the preoperative level, but
      significant weight regain was reported at long-term follow-up. 46% of
      participants reported recurrent loss of control over eating (objective or
      subjective bulimic episodes) on the EDE-Q. These patients constituted a
      distinctive subgroup with a less favorable outcome, including greater weight
      regain. CONCLUSION: Self-reported loss of control over eating was related to
      weight regain after GBP and may be an important target for clinical intervention.
      The relationship of binge eating and related psychopathology to outcome following
      GBP warrants further investigation.

PMID- 11975228
TI  - Systemic inflammatory response after laparoscopic and open application of
      adjustable banding for morbidly obese patients.
AB  - BACKGROUND: Surgical injury induces a systemic inflammatory metabolic-endocrine
      response that is proportional to the severity of the surgical stress. Compared
      with the conventional open method, laparoscopic surgery is mini-invasive and has
      decreased postoperative pain and length of hospitalization. The aim of this study
      was to investigate the systemic inflammatory response, after laparoscopic and
      open stoma-adjustable silicone band application, which is thought to be mediated
      by cytokines. METHOD: 30 morbidly obese patients underwent Swedish adjustable
      gastric banding (SAGB). 15 patients underwent laparoscopic (group 1) and 15 open
      SAGB (group 2). Mean operative time for the laparoscopic group was 70-110 min and
      for the laparotomy group 80-120 min. Gallbladders were not removed, and there
      were no systemic diseases in the patients. The intensity of surgical trauma was
      evaluated by measurement of metabolic and hormonal responses to the surgery.
      Plasma levels of C-reactive (CRP), haptoglobin, ceruloplasmin, albumin,
      transferrin, IL-6, malonic dialdehyde (MDA) and creatinine were measured before
      and after the operation. RESULTS: CRP and IL-6 levels increased during and after
      laparoscopic and open SAGB. However, postoperative responses were significantly
      greater after open SAGB (group 2) (p < 0.05). MDA level, an indicator of an
      oxidative trauma, was elevated in group 1 at the 6th postoperative hour but was
      significantly higher in group 2 at the 6th and 12th postoperative hours. The
      results were more significant in group 2 (p < 0.05). There was no statistical
      difference between groups 1 and 2 in terms of albumin, creatinine, and
      transferrin levels before and after surgery. CONCLUSION: The systemic
      inflammatory responses after laparoscopic SAGB were significantly reduced
      compared with those after open SAGB.

PMID- 11975229
TI  - Laparoscopic adjustable gastric banding: surgical and radiological approach.
AB  - BACKGROUND: The laparoscopically-placed adjustable gastric band (LAGB) is a
      minimally invasive, adjustable and completely reversible operation. We report 3
      years experience. METHODS: Between May 1998 and January 2001, we operated on a
      consecutive series of 50 patients (8 male/42 female). Mean age of patients was 37
      years (30-48). Mean preoperative BMI was 43 kg/m2 (range 38-55). RESULTS: Mean
      operative time was 130 minutes (range 75-150), and the conversion rate was 6%.
      Mean hospital stay was 2.8 days (range 2-10). Postoperatively 7/50 (14%) of
      patients had dysphagia and subsequently 2 (4%) developed gastric pouch
      dilatation. 2/50 (4%) had non-fatal pulmonary embolism and 2/50 (4%) developed
      gastroesophageal reflux. Overall morbidity was 32%. There has been no mortality.
      6 weeks postoperatively, patients had adjustment of the band by the radiologists.
      Follow-up has been up to 30 months. Mean excess weight loss at 6 months was 30%
      (range 26-35%, N = 50), at 12 months 52% (range 44-55%, N = 42), at 24 months 60%
      (range 55-65%, N = 14) and at 30 months 62% (range 58-64%, N = 8). 5 patients
      have reached their ideal body weight. CONCLUSIONS: LAGB is safe and effective,
      even early in the learning curve. The radiologist plays a distinct role. A multi
      disciplinary team approach is essential for optimal results. Long-term results
      are pending.

PMID- 11975230
TI  - A technique for prevention of port complications after laparoscopic adjustable
      silicone gastric banding.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding is a safe and effective
      treatment method for morbid obesity. Injection port dislocation, tube perforation
      and access port infection are generally classified among the minor complications,
      although they can require a reoperation at the port-site or even at the level of
      the band which may have to be removed. We designed a technique to fix the port,
      that can avoid unnecessary complications. METHODS: The port is sutured onto a
      polyprophlene mesh, which is then cut into shape and attached to the rectus
      fascia in the left hypochondrium with a Tacker stapling device. From February
      2000 to January 2001, 25 patients (BMI 35-60) were operated using this technique.
      RESULTS: No injection port dislocation, tube perforation or access port infection
      has been found in these patients. CONCLUSION: With the larger surface area by
      which the port is attached to the fascia, a stable position of the port is
      obtained and dislocation avoided. Multiple failed attempts at port access, with
      resulting risk of infection, are avoided. Due to port stability, risk of
      incidental tube perforation is reduced. Moreover, a considerable gain of time is
      obtained compared with the classical suturing of the port.

PMID- 11975231
TI  - Lower extremity compartment syndrome following a laparoscopic Roux-en-Y gastric
      bypass.
AB  - BACKGROUND: Bariatric surgery has the potential for serious complications. A case
      is presented of unilateral lower extremity compartment syndrome after a
      laparoscopic Roux-en-Y gastric bypass performed in the modified lithotomy
      position. CASE REPORT: A 38-year-old female (weight 134.5 kg, BMI 49.6) underwent
      a laparoscopic Roux-en-Y gastric bypass (operating time 375 min).
      Postoperatively, she complained of bilateral lower extremity pain that gradually
      subsided over the course of the day. However, on the 1st postoperative day she
      developed numbness on the dorsum of the foot and compartment syndrome was
      diagnosed (anterior compartment pressure 71 mmHg). She underwent emergency
      fasciotomy, which resulted in a reduction of the pain and numbness on the dorsum
      of the foot. The next day she ambulated without difficulty and was discharged
      home on the 5th postoperative day. 12 days after her operation, delayed primary
      closure of the fasciotomy wound was done with the assistance of a novel device
      (Proxiderm) that applies constant tension to the wound edges. Subsequent recovery
      was uneventful, and at 4-month follow-up the patient had a weight loss of 28 kg
      without any right leg motor or sensory deficits. CONCLUSION: Bariatric surgeons
      should be aware of compartment syndrome as a rare but serious complication.
      Prevention, early recognition, and prompt fasciotomy are crucial for a favorable
      outcome.

PMID- 11975232
TI  - Psychotherapeutic treatment of morbidly obese patients after gastric banding.
AB  - BACKGROUND: Surgery is the most effective therapeutic option for weight reduction
      in carefully selected patients with morbid obesity resistant to conventional
      treatment. However, surgical treatment is not the solution but an important
      precondition for successful management of morbid obesity. METHODS: All patients
      undergo a psychiatric examination before laparoscopic gastric banding. At the
      first examination we inform all patients about the various forms of psychological
      support offered before and especially after gastric banding. RESULTS: A majority
      of the obese individuals are interested in psychological support postoperatively,
      but only a minority of this patient group (about one-quarter) ultimately enlists
      psychological support on a regular or irregular basis. Some specific
      psychological topics have proved to be particularly important such as change of
      self-esteem as a consequence of weight loss, problems in adopting new eating
      behaviors and the risk for developing a new eating disordered behavior, and
      problems involving adequate problem-solving. CONCLUSIONS: In many cases, some
      form of psychological support is necessary in order to cope with the new
      postoperative demands and to find more adequate coping strategies for underlying
      psychological, psychosocial and environmental problems. The different kinds of
      psychological support and psychotherapeutic treatment available at Innsbruck
      University Hospital for obese patients after gastric banding are discussed here.

PMID- 11975233
TI  - Air test as an alternative to methylene blue test for leaks.

PMID- 11975234
TI  - First successful laparoscopic gastric band.

PMID- 11975235
TI  - Harry Potter and obesity.

PMID- 11975236
TI  - How two lives met in death.

PMID- 11975237
TI  - Inside Suicide, Inc.

PMID- 11975238
TI  - Sweeping changes.

PMID- 11975239
TI  - Don't write off care in the community. Interview by Ian McMillan.

PMID- 11975240
TI  - In the lead. Interview by Charlotte Alderman.

PMID- 11975241
TI  - One-stop service.

PMID- 11975242
TI  - Back on track. Interview by Alison Moore.

PMID- 11975243
TI  - All together now.

PMID- 11975244
TI  - Deliver the goods.

PMID- 11975245
TI  - Verifying a death.

PMID- 11975247
TI  - You can't slap your neighbour or wife, so why can parents hit their children?

PMID- 11975246
TI  - Lessons in care.

PMID- 11975248
TI  - All for a quiet night.

PMID- 11975251
TI  - Don't ignore health risk posed by rising cattle TB.

PMID- 11975252
TI  - Assessing and grading pressure ulcers.

PMID- 11975254
TI  - Practice development initiatives.

PMID- 11975255
TI  - Making a difference to practice: clinical benchmarking. Part 2.
AB  - In the second of two articles, the authors explore further the use of clinical
      practice benchmarking. In particular, practice related to improving nutritional
      care for patients, caring for patients with mental health needs and safely
      transferring critically ill patients is examined. The authors conclude by
      summarising the value of clinical practice benchmarking and how it made a
      difference to practice in their trust. The first article appeared in Nursing
      Standard last week.

PMID- 11975256
TI  - Using transactional analysis to understand the supervisory process.
AB  - Most literature on supervision praises its ability to create space for
      reflection, but seldom explores the disabling effects. Using the experiences of
      four nurses, this article makes use of Berne's Transactional Analysis model as a
      method for illuminating patterns within supervision. The article concludes that
      the confessional nature of clinical supervision reflects contemporary practice
      and the implications of supervision really appear to be an undercover policing or
      enforcement of cultural/management objectives.

PMID- 11975259
TI  - Intra-articular and soft tissue injections by nurses: preparation for expanded
      practice.
AB  - Administration of intra-articular and soft tissue injections for rheumatic
      disease represents an expansion of the nurse's role. To achieve the benefits of
      improved care for patients, and enhanced practice and job satisfaction for
      practitioners, preparation for the role must be rigorous and systematic. Here the
      authors describe a course designed to meet these criteria. They set out the
      content and outcomes of the course and consider some of the ethical and legal
      issues surrounding such role expansion.

PMID- 11975260
TI  - The older person with renal failure.
AB  - The number of older people with end-stage renal failure is increasing. Mark Bevan
      describes the implications this will have for renal nurses, and others working
      with elderly people in renal failure.

PMID- 11975262
TI  - Understanding type 2 diabetes.
AB  - Practice profiles are reflective pieces written by nurses in practice and based
      on continuing professional development articles. This week Susan Ackroyd
      discusses type 2 diabetes.

PMID- 11975268
TI  - A sense of frustration.

PMID- 11975269
TI  - Taking the lead.

PMID- 11975270
TI  - Spending power.

PMID- 11975271
TI  - Breathing space.

PMID- 11975272
TI  - Access denied. While the decision over beta-interferon prescribing hangs in the
      balance, one thing's for certain--nurses will be left to pick up the pieces.

PMID- 11975273
TI  - Oesophageal varices.

PMID- 11975274
TI  - Support network. The Internet is particularly useful for practice nurses working
      in isolation.

PMID- 11975275
TI  - Keep ahead of the game if you want to recommend quality Websites to patients.
      Follow the guide.

PMID- 11975277
TI  - Cervical screening: patients' negative attitudes and experiences.
AB  - BACKGROUND: This article explores the negative attitudes some women have towards
      the cervical screening programme. These attitudes could ultimately prevent them
      from participating in the programme. The negative experiences of women who
      receive a positive result are also explored. CONCLUSION: Women's negative
      attitudes towards cervical screening can largely be countered by improving their
      understanding of the process and diagnosis of cervical cancer. Women who receive
      a positive smear should be offered support to reduce their anxiety.

PMID- 11975278
TI  - An evaluation of temperature measurement.
AB  - Temperature measurement is an important diagnostic tool and must be carried out
      correctly for temperature changes to be detected. This article gives the results
      of an audit into temperature measurement and makes recommendations to ensure
      accurate and safe practice.

PMID- 11975279
TI  - Pressure sore prevention in nursing homes.
AB  - Staff working in nursing homes are caring for increasingly dependent residents
      who are consequently at great risk of developing pressure sores. Mary Clay offers
      a guide to the essential principles of pressure sore prevention as a teaching aid
      for all caring staff.

PMID- 11975281
TI  - Not for the faint-hearted. If you can rise to the challenge of prison nursing,
      you may well influence the care of disadvantaged people.

PMID- 11975283
TI  - Home economics.

PMID- 11975284
TI  - Will our paths cross?

PMID- 11975285
TI  - Not fit for the job.

PMID- 11975286
TI  - Champions' champion. Interview by Ruth Williams.

PMID- 11975287
TI  - User friendly. Interview by Ian McMillan.

PMID- 11975288
TI  - Seaside story.

PMID- 11975289
TI  - Timely intervention.

PMID- 11975290
TI  - Never made a mistake?

PMID- 11975291
TI  - Deception and lies.

PMID- 11975292
TI  - Sexuality and patients: breaking the last taboo.

PMID- 11975301
TI  - Tomorrow's nurses?

PMID- 11975302
TI  - Making a difference to practice: clinical benchmarking. Part 1.
AB  - In the first of two articles, the authors describe how an internal clinical
      practice benchmarking group was established in Preston to compare and share
      examples of best practice. The aim was to ensure consistent high standards of
      care practice across the trust. Activity related to discharge planning and
      visiting is used here to illustrate the effectiveness of clinical practice
      benchmarking as a continuous quality improvement tool. The second article will
      appear in Nursing Standard on May 3.

PMID- 11975303
TI  - Chaos, complexity and nursing.
AB  - Chaos and complexity theories have implications for nursing practice. Chaotic
      systems, potentially including health, the NHS and nursing, are governed by rules
      which should be understood in order to try to predict future behaviour.
      Complexity relates to the interconnectedness of things and fits neatly with the
      concept of holistic care. It can also make important contributions towards
      restructuring and reorganising nursing.

PMID- 11975308
TI  - Creating the right environment for return-to-practice candidates.
AB  - With a recognised national shortage of qualified nurses in England, a trust and
      university joined forces to provide a return-to-nursing course (ENB 902). This
      article describes how they provided clinical support and encouraged nurses to
      return to practice.

PMID- 11975309
TI  - Safe use of glutaraldehyde.
AB  - Glutaraldehyde is an effective chemical for killing micro-organisms that is used
      in a variety of healthcare settings to rapidly clean instruments. It is highly
      toxic in even small concentrations and needs to stored and handled carefully.
      Diane Romano-Woodward explains how nurses can ensure that adequate precautions
      are taken to prevent harm to staff and patients.

PMID- 11975310
TI  - Care of foot ulcers in the diabetic patient.
AB  - Practice profiles are reflective pieces written by nurses in practice, and based
      on continuing professional development articles. This week Sian Davies discusses
      diabetic foot ulcers.

PMID- 11975311
TI  - Great minds think alike.

PMID- 11975314
TI  - Leader of the pack.

PMID- 11975321
TI  - [Breast cancer in women with trisomy 21].
AB  - The population with Down's syndrome has a different cancer profile compared to
      the general population, even after taking into account issues of survival and
      ageing. Several solid tumours are unusually rare, whereas in contrast leukaemias
      are increased. In addition, few studies are available on this topic. We therefore
      decided to conduct a mortality study based on the INSERM national mortality
      statistics in France comparing over a 24 year period deaths from female breast
      cancer in the general French population with the cancer deaths in women with
      Down's syndrome. Only 5 deaths with Down's syndrome could be found compared to
      68.98 expected based on national statistics. This clear reduction in risk agrees
      with other studies available in Down's syndrome patients. This observation could
      be partly explained by over expression of genes linked to gene dosage effects on
      chromosome 21, playing a role in cell growth, differentiation, survival and
      death. An additional protective effect could come from the marked and continued
      decreased exposure to oestrogens, starting in utero for women with trisomy 21 and
      lasting all over life.

PMID- 11975322
TI  - [Access of developing countries to essential drugs: a process of equity].
AB  - In the context of the fight against poverty, the access of developing countries
      to essential drugs mobilizes the international community. It leads to envisage
      new and intricates politics. If donations or tiered prices are studied, the
      manufacturing of generics and even of patented drugs through voluntary or
      compulsory licensing is evoked. At a longer terms, it's the setting of health
      national politics and industrialisation which are concerned. These new
      orientations are not without consequence on the global drug market.

PMID- 11975323
TI  - [Intrauterine growth retardation, its consequences in infancy, in the child and
      long term].
AB  - The authors report the consequence of intra-uterine growth retardation on infancy
      and adult disease. During infancy in 7 to 10% of cases a growth retardation less
      than -2 DS, is observed and subsequently needs growth hormone treatment. In adult
      X syndrome (hypertension, diabetes of 2 types insulino resistant and
      cardiovascular disease) is observed 18 times more in subjects where the birth
      weight was low than 2.4 kg. Finally the authors give some recommendations to
      follow-up of the infants born with a growth restriction.

PMID- 11975324
TI  - [Role of growth factor signaling in epithelial cell plasticity during development
      and in carcinogenesis].
AB  - The work described in this review addresses the multifunctional roles of growth
      factors and their cognate receptors in normal development and in tumorigenesis.
      The concept of epithelial cell plasticity is described in the context of
      embryonic development during which frequent remodeling occurs in epithelial
      tissues. The critical role of one member of the FGF family of growth factors is
      demonstrated in lung branching morphogenesis. Several members of this family have
      been shown to induce an epithelial-mesenchymal transition in a bladder carcinoma
      line. In vivo the same factors act in an autocrine or paracrine mode to favor
      tumor progression. It is suggested that an EGFR-ligand autocrine loop exerts a
      positive role in tumor progression of human bladder carcinoma whereas FGFR2 acts
      as a phenotypic tumor suppressor gene. Unexpectedly, constitutive activating
      mutations in FGFR3 have been uncovered in the majority of the Ta superficial
      tumors which progress only very rarely to the invasive stages. In contrast, in
      situ carcinoma, which are considered to be associated with a strong malignant
      potential, do not carry the FGFR3 mutations. The presence or absence of the
      mutations defines two distinct oncogenic pathways in bladder carcinogenesis. The
      studies reveal the complexities in defining the putative functions of growth
      factors at different times and differentiation stages during development and in
      tumor progression. These results emphasize the need for caution in the
      interpretation of studies evaluating the potential of novel anti-cancer agents
      and for better designs of in vitro and in vivo biological assays.

PMID- 11975325
TI  - [Radical trachelectomy: an operation that preserves the fertility of young women
      with invasive cervical cancer].
AB  - Surgery for epithelial cancer is more and more getting a tailored surgery: wide
      local excision of the primary and focused retrieval of the regional lymph nodes.
      As far as cancer of the cervix is concerned such a strategy is avoidable:
      laparosopic pelvic lymphadenectomy and radical trachelectomy. This operation is a
      variant of the classical Schauta operation. The difference is the uterus is
      divided underneath the isthmus which is, at the end of the operation, stitched to
      the vagina. A personal series of 82 cases gathered between 1987 and 2000 is
      reported. The number of recurrences is three. All of them have been registered in
      the population of 21 patients who were affected by a cancer two cm or more large.
      Among the 38 patients who wanted and were able to become pregnant 29 succeeded.
      Among the 47 registered pregnancies 35 went on after the 14th week and 27
      finished with the birth of a living baby.

PMID- 11975326
TI  - [Biological crisis at the end of the Cretaceous and the extinction of the
      dinosaurs. Validity of the cosmic hypothesis].
AB  - The history of life, which appeared more than 500 million years ago, has been
      characterized by a constant faunal and floral turnover. On five occasions, the
      background extinctions has become a mass extinction (ME), i.e. a major biotic
      crisis collapsing the upward curve of the biodiversity. The mass extinction of
      the end of the Permian is the most murderous but the end-Cretaceous one, which
      experiences dinosaur's death, is the most well-known. In fact, these land
      dwelling reptiles with upright limbs, as well as the pterosaurs, the mosasaurs
      and numerous invertebrates die as far as the last. There exists a lot of
      hypotheses tending to explain their death but they are often extravagant and/or
      impossible to be verified. The last one, referring to a collapse between the
      earth and a heavenly large bolide has given rise, since more than 20 years, to
      heated debates between catastrophists and gradualists, even if the reality of the
      impact seems no more doubtful (discovery of Chicxulub impact crater, iridium
      anomaly, tektite glass, shocked quartz, spinels with high nickel concentrations).
      It is now the extent of the deleterious effects (regional or worldwide
      repercussion) which is debating. By referring to the obtained data in oceanic
      environment and, if necessary, in terrestrial environment where fossil record is
      too often incomplete, it can be noticed an important fact corresponding to a
      selective character of extinctions, the event of the C/T boundary killing off
      some taxa while others are preserved. This remark does not really correspond to
      the hypothesis of a sudden planetary catastrophe of large magnitude.
      Consequently, it seems to be reasonable to make arise intrinsic factors
      associated to the dynamics of the globe (volcanic eruptions, marine regression,
      fall of temperature) over a long period. The collapse with the Chicxulub asteroid
      should then come up, especially in Western North-America, as a "coup de grace" in
      a weakened ecosystem.

PMID- 11975327
TI  - [Professor Jules Gavarret (1809-1890) and the application of mathematics and
      physics to medicine].
AB  - Professor Jules Gavarret has undertaken pretigious offices, has accumulated
      various titles and honours and has left an abundant bibliography about physics
      and chemistry of life phenomenon. To recount the career of one of the academics
      who were benefited the traditional medicine of the progress achieved in physical
      and mathematical sciences give us the opportunity of recalling one of the great
      Parisian personalities of 19th Century who had not been appreciated for too long.

PMID- 11975328
TI  - Phylogeny of lichen- and non-lichen-forming omphalinoid mushrooms and the utility
      of testing for combinability among multiple data sets.
AB  - As an initial step toward developing a model system to study requirements for and
      consequences of transitions to mutualism, the phylogeny of a group of closely
      related lichenized and nonlichenized basidiomycetes (Omphalina) was
      reconstructed. The phylogenetic analyses are based on four data sets representing
      different regions of the nuclear ribosomal repeat unit (ITS1, 5.8S, ITS2, and
      25S) obtained from 30 species of Omphalina and related genera. The resulting
      phylogenetic trees from each of these four data sets, when analyzed separately,
      were not identical. Testing for the combinability of these four data sets
      suggested that they could not be combined in their entirety. The removal of
      ambiguous alignments and saturated sites was sufficient, after reapplying the
      combinability test on the pruned data sets, to explain the topological
      discrepancies. In this process, the first of two complementary tests developed by
      Rodrigo et al. (1993, N.Z. J. Bot. 31:257-268) to assess whether two data sets
      are the result of the same phylogenetic history was found to be biased, rejecting
      the combinability of two data sets even when they are samples of the same
      phylogenetic history. Combining the four pruned data sets yielded phylogenies
      that suggest the five lichen-forming species of Omphalina form a monophyletic
      group. The sister group to this symbiotic clade consists mostly of dark brown
      Omphalina species intermixed with species from the genera Arrhenia and
      Phaeothellus. The genera Omphalina and Gerronema are shown to be polyphyletic.
      The lichen-forming species O. ericetorum and the nonmutualistic species O.
      velutipes, O. epichysium, and O. sphagnicola are the best candidates for
      experimental work designed to gain a better understanding of mechanisms involved
      in symbiotic interactions and the role symbiosis has played in the evolution of
      fungi.

PMID- 11975329
TI  - Phylogeography and molecular systematics of the Peromyscus aztecus species group
      (Rodentia: Muridae) inferred using parsimony and likelihood.
AB  - Mice of the Peromyscus aztecus species group occur at mid to high elevations in
      several mountain ranges in the highlands of Middle America (Mexico and Central
      America), a region of high endemicity. We examined the biogeography of this group
      by conducting phylogenetic analyses of 668 bp of the mitochondrial cytochrome b
      (cyt b) gene. Phylogenetic analyses under both parsimony and likelihood
      frameworks produced the same topologies, but estimates of nodal support were
      artificially high in weighted parsimony analyses. This difference is attributed
      to the inability of parsimony to optimize branch lengths when evaluating
      topologies. These data indicate that the P. aztecus-like populations from south
      and east of the Isthmus of Tehuantepec currently assigned to P. a. oaxacensis
      represent a distinct species, with genetic distances as high as 0.091. In
      addition, P. hylocetes is strongly divergent from Mexican populations of P.
      aztecus (genetic distances of 0.044-0.069), supporting the recognition of this
      taxon as a distinct species. The history of divergence in this group can be
      explained by a series of apparently early to middle Pleistocene vicariance events
      associated with glacial cycles. The Sierra Madre Occidental and Cordillera
      Transvolcanica each appear to be faunistically isolated, the Isthmus of
      Tehuantepec appears to have been a strong Pleistocene barrier, and the Sierra
      Madre Oriental has affinities with the Sierra Madre del Sur and the highlands of
      central Oaxaca.

PMID- 11975330
TI  - Is congruence between data partitions a reliable predictor of phylogenetic
      accuracy? Empirically testing an iterative procedure for choosing among
      phylogenetic methods.
AB  - The relationship between phylogenetic accuracy and congruence between data
      partitions collected from the same taxa was explored for mitochondrial DNA
      sequences from two well-supported vertebrate phylogenies. An iterative procedure
      was adopted whereby accuracy, phylogenetic signal, and congruence were measured
      before and after modifying a simple reconstruction model, equally weighted
      parsimony. These modifications included transversion parsimony, successive
      weighting, and six-parameter parsimony. For the data partitions examined, there
      is a generally positive relationship between congruence and phylogenetic
      accuracy. If congruence increased without decreasing resolution or phylogenetic
      signal, this increased congruence was a good predictor of accuracy. If congruence
      increased as a result of poor resolution, the degree of congruence was not a good
      predictor of accuracy. For all sets of data partitions, six-parameter parsimony
      methods show a consistently positive relationship between congruence and
      accuracy. Unlike successive weighting, six-parameter parsimony methods were not
      strongly influenced by the starting tree.

PMID- 11975331
TI  - Morphology, fossils, divergence timing, and the phylogenetic relationships of
      Gavialis.
AB  - Although morphological data have historically favored a basal position for the
      Indian gharial (Gavialis gangeticus) within Crocodylia and a Mesozoic divergence
      between Gavialis and all other crocodylians, several recent molecular data sets
      have argued for a sister-group relationship between Gavialis and the Indonesian
      false gharial (Tomistoma schlegelii) and a divergence between them no earlier
      than the Late Tertiary. Fossils were added to a matrix of 164 discrete
      morphological characters and subjected to parsimony analysis. When morphology was
      analyzed alone, Gavialis was the sister taxon of all other extant crocodylians
      whether or not fossil ingroup taxa were included, and a sister-group relationship
      between Gavialis and Tomistoma was significantly less parsimonious. In
      combination with published sequence and restriction site fragment data, Gavialis
      was the sister taxon of all other living crocodylians, but the position of
      Tomistoma depended on the inclusion of fossil ingroup taxa; with or without
      fossils, preferred morphological and molecular topologies were not significantly
      different. Fossils closer to Gavialis than to Tomistoma can be recognized in the
      Late Cretaceous, and fossil relatives of Tomistoma are known from the basal
      Eocene, strongly indicating a divergence long before the Late Tertiary.
      Comparison of minimum divergence time from the fossil record with different
      measures of molecular distance indicates evolutionary rate heterogeneity within
      Crocodylia. Fossils strongly contradict a post-Oligocene divergence between
      Gavialis and any other living crocodylian, but the phylogenetic placement of
      Gavialis is best viewed as unresolved.

PMID- 11975332
TI  - Trees within trees: genes and species, molecules and morphology.
AB  - The construction and interpretation of gene trees is fundamental in molecular
      systematics. If the gene is defined in a historical (coalescent) sense, there can
      be multiple gene trees within the single contiguous set of nucleotides, and
      attempts to construct a single tree for such a sequence must deal with homoplasy
      created by conflict among divergent histories. On a larger scale, incongruence is
      expected among gene tree topologies at different loci of individuals within
      sexually reproducing species, and it has been suggested that this discordance can
      be used to delimit species. A practical concern for such topological methods is
      that polymorphisms may be maintained through numerous cladogenic events; this
      polymorphism problem is less of a concern for nontopological approaches to
      species delimitation using molecular data. Although a central theoretical concern
      in molecular systematics is discordance between a given gene tree and the true
      "species tree," the primary empirical problem faced in reconstructing taxic
      phylogeny is incongruence among the trees inferred from different sequences.
      Linkage relationships limit character independence and thus have important
      implications for handling multiple data sets in phylogenetic analysis,
      particularly at the species level, where incongruence among different
      historically associated loci is expected. Gene trees can also be reconstructed
      for loci that influence phenotypic characters, but there is at best a tenuous
      relationship between phenotypic homoplasy and homoplasy in such gene trees.
      Nevertheless, expression patterns and orthology relationships of genes involved
      in the expression of phenotypes can in theory provide criteria for homology
      assessment of morphological characters.

PMID- 11975333
TI  - Analyzing large data sets: rbcL 500 revisited.

PMID- 11975334
TI  - DNA synapomorphies for a variety of taxonomic levels from a cosmid library from
      the New World bat Macrotus waterhousii.
AB  - An effective method yielding taxon-specific markers from the genome of a single
      individual would be valuable for many types of scientific investigations,
      including systematic, forensic, conservation, and evolutionary studies. We
      explored the use of cosmid libraries, with insert sizes averaging 35 kb, to
      streamline the process of locating sequences of DNA that can serve as taxonomic
      markers from the specific to the ordinal levels. By screening approximately 2.6%
      of the leaf-nosed bat (Macrotus waterhousii) genome, we identified several
      potential DNA fragments that appear to be synapomorphic for a variety of
      taxonomic levels. A more thorough analysis of the markers documented that 17
      Macrotus-specific clones represent three distinct DNA generic markers, whereas 30
      microchiropteran clones represent multiple copies of a single family of
      repetitive DNA. The Microchiroptera taxon markers hybridize with representatives
      of most of the Microchiroptera families; however, no hybridization was detected
      for members of the superfamily Rhinolophoidea. These results demonstrate that
      cosmid libraries can be a valuable source for isolating taxon-specific markers
      from mammals even when the insert size is as large as 35 kb.

PMID- 11975335
TI  - NEXUS: an extensible file format for systematic information.
AB  - NEXUS is a file format designed to contain systematic data for use by computer
      programs. The goals of the format are to allow future expansion, to include
      diverse kinds of information, to be independent of particular computer operating
      systems, and to be easily processed by a program. To this end, the format is
      modular, with a file consisting of separate blocks, each containing one
      particular kind of information, and consisting of standardized commands. Public
      blocks (those containing information utilized by several programs) house
      information about taxa, morphological and molecular characters, distances,
      genetic codes, assumptions, sets, trees, etc.; private blocks contain information
      of relevance to single programs. A detailed description of commands in public
      blocks is given. Guidelines are provided for reading and writing NEXUS files and
      for extending the format.

PMID- 11975336
TI  - Molecular systematics of the Canidae.
AB  - Despite numerous systematic studies, the relationships among many species within
      the dog family, Canidae, remain unresolved. Two problems of broad evolutionary
      significance are the origins of the taxonomically rich canidae fauna of South
      America and the development in three species of the trenchant heel, a unique meat
      cutting blade on the lower first molar. The first problem is of interest because
      the fossil record provides little evidence for the origins of divergent South
      American species such as the maned wolf and the bush dog. The second issue is
      problematic because the trenchant heel, although complex in form, may have
      evolved independently to assist in the processing of meat. We attempted to
      resolve these two issues and five other specific taxonomic controversies by
      phylogenetic analysis of 2,001 base pairs of mitochondrial DNA (mtDNA) sequence
      data from 23 canidae species. The mtDNA tree topology, coupled with data from the
      fossil record, and estimates of rates of DNA sequence divergence suggest at least
      three and possibly four North American invasions of South America. This result
      implies that an important chapter in the evolution of modern canids remains to be
      discovered in the fossil record and that the South American canidae endemism is
      as much the result of extinction outside of South America as it is due to
      speciation within South America. The origin of the trenchant heel is not well
      resolved by our data, although the maximum parsimony tree is weakly consistent
      with a single origin followed by multiple losses of the character in several
      extant species. A combined analysis of the mtDNA data and published morphological
      data provides unexpected support for a monophyletic South American canidae clade.
      However, the homogeneity partition tests indicate significant heterogeneity
      between the two data sets.

PMID- 11975337
TI  - Multiple sources of character information and the phylogeny of Hawaiian
      drosophilids.
AB  - Relationships among representatives of the five major Hawaiian Drosophila species
      groups were examined using data from eight different gene regions. A simultaneous
      analysis of these data resulted in a single most-parsimonious tree that (1)
      places the adiastola picture-winged subgroup as sister taxon to the other picture
      winged subgroups, (2) unites the modified-tarsus species group with flies from
      the Antopocerus species group, and (3) places the white-tip scutellum species
      group as the most basal taxon. Because of the different gene sources used in this
      study, numerous process partitions can be erected within this data set. We
      examined the incongruence among these various partitions and the ramifications of
      these data for the taxonomic consensus, prior agreement, and simultaneous
      analysis approaches to phylogenetic reconstruction. Separate analyses and
      taxonomic consensus appear to be inadequate methods for dealing with the
      partitions in this study. Although detection of incongruence is possible and
      helps elucidate particular areas of disagreement among data sets, separation of
      partitions on the basis of incongruence is problematic for many reasons. First,
      analyzing all genes separately and then either presenting them all as possible
      hypotheses or taking their consensus provides virtually no information concerning
      the relationships among these flies. Second, despite some evidence of
      incongruence, there are no clear delineations among the various gene partitions
      that separate only heterogeneous data. Third, to the extent that problematic
      genes can be identified, these genes have nearly the same information content,
      within a combined analysis framework, as the remaining nonproblematic genes. Our
      data suggest that significant incongruence among data partitions may be isolated
      to specific relationships and the "false" signal creating this incongruence is
      most likely to be overcome by a simultaneous analysis. We present a new method,
      partitioned Bremer support, for examining the contribution of a particular data
      partition to the topological support of the simultaneous analysis tree.

PMID- 11975338
TI  - Evolution and phylogeny of the Diptera: a molecular phylogenetic analysis using
      28S rDNA sequences.
AB  - Portions of the large ribosomal subunit RNA gene (28S rDNA) encompassing the D1
      and the D7 region were obtained from 16 dipteran species and families to
      reconstruct early phylogenetic events in the order Diptera. For outgroup
      comparison, the corresponding sequences were used from representative taxa of the
      Siphonaptera, Mecoptera, and Lepidoptera. A subset of 488 unambiguously alignable
      sites was analyzed with respect to important sequence evolution parameters. We
      found (1) sequence variability is significantly higher in double-stranded sites
      than in single-stranded sites, (2) transitions are close to saturation in most
      pairwise sequence comparisons, (3) significant substitution rate heterogeneity
      exists across sites, and (4) significant substitution rate heterogeneity exists
      among lineages. Tree reconstruction was carried out with the neighbor joining,
      maximum parsimony, and maximum likelihood methods. Four major subgroups are
      consistently and robustly supported: the Brachycera, the Culicomorpha, the
      Tipulomorpha sensu stricto, and the hitherto controversial Bibionomorpha sensu
      lato, which includes the families Sciaridae, Mycetophilidae, Cecidomyiidae,
      Bibionidae, Scatopsidae, and Anisopodidae. The phylogenetic relationships within
      or among these subclades and the positions of the families Psychodidae and
      Trichoceridae were not robustly resolved. These results support the view that the
      mouthparts of extant dipteran larvae evolved from a derived ground state
      characterized by subdivided and obliquely moving mandibles. Furthermore, sequence
      divergence and the paleontological record consistently indicate that a period of
      rapid cladogenesis gave rise to the major dipteran subgroups.

PMID- 11975339
TI  - Phylogenetic analyses of DNA and allozyme data suggest that Gonioctena leaf
      beetles (Coleoptera; Chrysomelidae) experienced convergent evolution in their
      history of host-plant family shifts.
AB  - A phylogenetic analysis of the genus Gonioctena (Coleoptera, Chrysomelidae) based
      on allozyme data (17 loci) and mitochondrial DNA sequence data (three gene
      fragments, 1,391 sites) was performed to study the evolutionary history of host
      plant shifts among these leaf beetles. This chrysomelid genus is
      characteristically associated with a high number of different plant families. The
      diverse molecular data gathered in this study are to a large extent congruent,
      and the analyses provide a well-supported phylogenetic hypothesis to address
      questions about the evolution of host-plant shifts in the genus Gonioctena. The
      most-parsimonious reconstruction of the ancestral host-plant associations, based
      on the estimated phylogeny, suggests that the Fabaceae was the ancestral host
      plant family of the genus. Although most of the host-plant shifts (between
      different host species) in Gonioctena have occurred within the same plant family
      or within the same plant genus, at least eight shifts have occurred between hosts
      belonging to distantly related and chemically dissimilar plant families. In these
      cases, host shifts may have been simply directed toward plant species available
      in the environment. Yet, given that two Gonioctena lineages have independently
      colonized the same three new plant families (Salicaceae, Betulaceae, Rosaceae),
      including four of the same new genera (Salix, Alnus, Prunus, Sorbus), some
      constraints are likely to have limited the different possibilities of
      interfamilial host-plant shifts.

PMID- 11975340
TI  - Process partitions, congruence, and the independence of characters: inferring
      relationships among closely related Hawaiian Drosophila from multiple gene
      regions.

PMID- 11975341
TI  - Prior agreement: arbitration or arbitrary?

PMID- 11975342
TI  - Tests of turtle phylogeny: molecular, morphological, and paleontological
      approaches.
AB  - We present phylogenetic analyses of both molecular and morphological data for the
      23 major lineages of living turtles and seven key fossil taxa. Nearly 1 kilobase
      of cytochrome b sequence, 325 base pairs of 12S ribosomal DNA, and 115
      morphological characters contained similar phylogenetic information, although
      each provided unique information on different nodes of chelonian history. A
      character-based combinability test (implemented in PAUP*) and a non-parametric
      test of taxonomic congruence indicated no strong evidence for heterogeneity among
      data sets, and we used a combined approach to estimate a final phylogeny of the
      major lineages of living turtles. This approach resulted in a very well-resolved
      tree, with only a few of the deep branches within the Cryptodira left as an
      unresolved polytomy. The addition of six relatively complete fossils chosen to
      help resolve this basal polytomy provided little added resolution to the tree and
      resulted in a sharp decline in bootstrap proportions for nodes near the fossils.
      Branch-length analysis and independent dates from the fossil record suggest that
      these unresolved nodes may represent a rapid radiation of the major cryptodiran
      lineages 90-120 million years ago.

PMID- 11975343
TI  - A new nuclear gene for insect phylogenetics: dopa decarboxylase is informative of
      relationships within Heliothinae (Lepidoptera: Noctuidae).
AB  - The lack of a readily accessible roster of nuclear genes informative at various
      taxonomic levels is a bottleneck for molecular systematics. In this report, we
      describe the first phylogenetic application of the sequence that encodes the
      enzyme dopa decarboxylase (DDC). For 14 test species within the noctuid moth
      subfamily Heliothinae that represent the previously best-supported groupings, a
      690-bp fragment of DDC resolved relationships that are largely concordant with
      prior evidence from elongation factor-1 alpha (EF-1 alpha), morphology, and
      allozymes. Although both synonymous and nonsynonymous changes occur in DDC
      substantially more rapidly than they do in EF-1 alpha, DDC divergences within
      Heliothinae are below saturation at all codon positions. Analysis of DDC and EF-1
      alpha in combination resulted in increased bootstrap support for several
      groupings. As a first estimate of previously unresolved relationships, DDC
      sequences were analyzed from 16 additional heliothines, for a total of 30
      heliothine species plus outgroups. Previous relationships based on DDC were
      generally stable with increased taxon sampling, although a two- to eightfold
      downweighting of codon position 3 was required for complete concordance with the
      14-species result. The weighted strict consensus trees were largely resolved and
      were congruent with most although not all previous hypotheses based on either
      morphology or EF-1 alpha. The proposed phylogeny suggests that the major
      agricultural pest heliothines belong to a single clade, characterized by
      polyphagy and associated life history traits, within this largely host-specific
      moth subfamily. DDC holds much promise for phylogenetic analysis of Tertiary-age
      animal groups.

PMID- 11975344
TI  - Molecular systematics of short-horned lizards: biogeography and taxonomy of a
      widespread species complex.
AB  - We surveyed mitochondrial DNA (mtDNA) sequence variation in short-horned lizards
      (Phrynosoma douglasi) from throughout western North America and used these data
      to estimate an intraspecific phylogeny and to assess biogeographic scenarios
      underlying the geographic structure of lineages in this species. We sequenced 783
      base pairs from 38 populations of P. douglasi and three putative outgroups (P.
      ditmarsi, P. orbiculare, P. platyrhinos). We detected high levels of nucleotide
      variation among populations and a spatial distribution of mtDNA lineages
      compatible with major geographic regions. The phylogenetic hypotheses best
      supported by the data suggest that P. douglasi, as currently described, is
      paraphyletic with respect to P. ditmarsi. Populations of P. douglasi from the
      Pacific Northwest (ID, CA, OR, WA) form a monophyletic group that is sister to
      the subsequent radiation of P. ditmarsi and other P. douglasi clades. These
      results suggest that divergences within this widespread species are fairly old.
      We focused on the genetic structure of populations of P. douglasi from a
      geographic perspective and interpreted the intraspecific phylogeny in light of
      geologic and climatic changes in western North America during the last 20 million
      years. The generally high levels of genetic variation found in these population
      comparisons are in accord with high levels of morphological variation in this
      species group; however, only in the Pacific Northwest region is there spatial
      congruence between these phylogenetic results and subspecific ranges based on
      previous morphological studies. We compared the evolutionary units delineated in
      this study with previously described subspecies of P. douglasi and evaluated the
      support (from morphology and mtDNA) for each population lineage in the phylogeny
      and the implications for the taxonomy of this group.

PMID- 11975345
TI  - Site-by-site estimation of the rate of substitution and the correlation of rates
      in mitochondrial DNA.
AB  - A maximum likelihood method for independently estimating the relative rate of
      substitution at different nucleotide sites is presented. With this method, the
      evolution of DNA sequences can be analyzed without assuming a specific
      distribution of rates among sites. To investigate the pattern of correlation of
      rates among sites, the method was applied to a data set consisting of the protein
      coding regions of the mitochondrial genome from 10 vertebrate species. Rates
      appear to be strongly correlated at distances up to 40 codons apart. Furthermore,
      there appears to be some higher order correlation of sites approximately 75
      codons apart. The method of site-by-site estimation of the rate of substitution
      may also be applied to examine other aspects of rate variation along a DNA
      sequence and to assess the difference in the support of a tree along the
      sequence.

PMID- 11975346
TI  - On the consistency of maximum likelihood estimation of phylogenetic trees from
      nucleotide sequences.

PMID- 11975347
TI  - The Strepsiptera problem: phylogeny of the holometabolous insect orders inferred
      from 18S and 28S ribosomal DNA sequences and morphology.
AB  - Phylogenetic relationships among the holometabolous insect orders were inferred
      from cladistic analysis of nucleotide sequences of 18S ribosomal DNA (rDNA) (85
      exemplars) and 28S rDNA (52 exemplars) and morphological characters. Exemplar
      outgroup taxa were Collembola (1 sequence), Archaeognatha (1), Ephemerida (1),
      Odonata (2), Plecoptera (2), Blattodea (1), Mantodea (1), Dermaptera (1),
      Orthoptera (1), Phasmatodea (1), Embioptera (1), Psocoptera (1), Phthiraptera
      (1), Hemiptera (4), and Thysanoptera (1). Exemplar ingroup taxa were Coleoptera:
      Archostemata (1), Adephaga (2), and Polyphaga (7); Megaloptera (1); Raphidioptera
      (1); Neuroptera (sensu stricto = Planipennia): Mantispoidea (2), Hemerobioidea
      (2), and Myrmeleontoidea (2); Hymenoptera: Symphyta (4) and Apocrita (19);
      Trichoptera: Hydropsychoidea (1) and Limnephiloidea (2); Lepidoptera: Ditrysia
      (3); Siphonaptera: Pulicoidea (1) and Ceratophylloidea (2); Mecoptera: Meropeidae
      (1), Boreidae (1), Panorpidae (1), and Bittacidae (2); Diptera: Nematocera (1),
      Brachycera (2), and Cyclorrhapha (1); and Strepsiptera: Corioxenidae (1),
      Myrmecolacidae (1), Elenchidae (1), and Stylopidae (3). We analyzed approximately
      1 kilobase of 18S rDNA, starting 398 nucleotides downstream of the 5' end, and
      approximately 400 bp of 28S rDNA in expansion segment D3. Multiple alignment of
      the 18S and 28S sequences resulted in 1,116 nucleotide positions with 24 insert
      regions and 398 positions with 14 insert regions, respectively. All Strepsiptera
      and Neuroptera have large insert regions in 18S and 28S. The secondary structure
      of 18S insert 23 is composed of long stems that are GC rich in the basal
      Strepsiptera and AT rich in the more derived Strepsiptera. A matrix of 176
      morphological characters was analyzed for holometabolous orders. Incongruence
      length difference tests indicate that the 28S + morphological data sets are
      incongruent but that 28S + 18S, 18S + morphology, and 28S + 18S + morphology fail
      to reject the hypothesis of congruence. Phylogenetic trees were generated by
      parsimony analysis, and clade robustness was evaluated by branch length, Bremer
      support, percentage of extra steps required to force paraphyly, and sensitivity
      analysis using the following parameters: gap weights, morphological character
      weights, methods of data set combination, removal of key taxa, and alignment
      region. The following are monophyletic under most or all combinations of
      parameter values: Holometabola, Polyphaga, Megaloptera + Raphidioptera,
      Neuroptera, Hymenoptera, Trichoptera, Lepidoptera, Amphiesmenoptera (Trichoptera
      + Lepidoptera), Siphonaptera, Siphonaptera + Mecoptera, Strepsiptera, Diptera,
      and Strepsiptera + Diptera (Halteria). Antliophora (Mecoptera + Diptera +
      Siphonaptera + Strepsiptera), Mecopterida (Antliophora + Amphiesmenoptera), and
      Hymenoptera + Mecopterida are supported in the majority of total evidence
      analyses. Mecoptera may be paraphyletic because Boreus is often placed as sister
      group to the fleas; hence, Siphonaptera may be subordinate within Mecoptera. The
      18S sequences for Priacma (Coleoptera: Archostemata), Colpocaccus (Coleoptera:
      Adephaga), Agulla (Raphidioptera), and Corydalus (Megaloptera) are nearly
      identical, and Neuropterida are monophyletic only when those two beetle sequences
      are removed from the analysis. Coleoptera are therefore paraphyletic under almost
      all combinations of parameter values. Halteria and Amphiesmenoptera have high
      Bremer support values and long branch lengths. The data do not support placement
      of Strepsiptera outside of Holometabola nor as sister group to Coleoptera. We
      reject the notion that the monophyly of Halteria is due to long branch attraction
      because Strepsiptera and Diptera do not have the longest branches and there is
      phylogenetic congruence between molecules, across the entire parameter space, and
      between morphological and molecular data.

PMID- 11975348
TI  - An alternating least squares approach to inferring phylogenies from pairwise
      distances.
AB  - A computational method is presented for minimizing the weighted sum of squares of
      the differences between observed and expected pairwise distances between species,
      where the expectations are generated by an additive tree model. The criteria of
      Fitch and Margoliash (1967, Science 155:279-284) and Cavalli-Sforza and Edwards
      (1967, Evolution 21:550-570) are both weighted least squares, with different
      weights. The method presented iterates lengths of adjacent branches in the tree
      three at a time. The weighted sum of squares never increases during the process
      of iteration, and the iterates approach a stationary point on the surface of the
      sum of squares. This iterative approach makes it particularly easy to maintain
      the constraint that branch lengths never become negative, although negative
      branch lengths can also be allowed. The method is implemented in a computer
      program, FITCH, which has been distributed since 1982 as part of the PHYLIP
      package of programs for inferring phylogenies, and is also implemented in PAUP*.
      The present method is compared, using some simulated data sets, with an
      implementation of the method of De Soete (1983, Psychometrika 48:621-626); it is
      slower than De Soete's method but more effective at finding the least squares
      tree. The relationship of this method to the neighbor-joining method is also
      discussed.

PMID- 11975349
TI  - Vagaries in the delimitation of character states in quantitative variation--an
      experimental study.
AB  - An experimental study on the delimitation of character states in continuous
      variation indicates that (1) the way data are presented influences the assignment
      of character states and (2) states in the same data set are delimited in various
      ways by different individuals. Forty-nine individuals were given a set of graphs
      denoting variation of 10 characters in the genus Kalmia (Ericaceae) and
      outgroups, all identification having been removed from the graphs. The variation
      was represented in one of three ways: as 95% confidence intervals on a linear
      scale, as 95% confidence intervals on a log10 scale, or with bars showing SD x 2
      on a linear scale. No two individuals scored a set of graphs in the same way, and
      only one character in one representation was scored identically by all
      individuals; the scoring for this character was completely different when the
      ordinate was changed from linear to logarithmic. Together, the 49 individuals
      delimited states within each character between 9 and 16 different ways. In
      general, variation represented by 2 x SD bars elicited the largest numbers of
      different scorings, yet with a relatively low number of states; the complexity of
      the patterns in the graphs in this representation was greatest. Expert knowledge
      appears to be of dubious value in delimiting states in such variation, and if
      such characters are to be used in phylogenetic analyses, states could be
      delimited by people who know nothing of the details of the study being scored; in
      any case, presentation of data and an explicit protocol to follow when delimiting
      states are essential. In converting data of this type into character states,
      psychological factors are particularly likely to come into play. Other
      implications of our experiments include the severe underdetermination of some
      phylogenetic hypotheses by observation and the heterogeneous nature of
      morphological data.

PMID- 11975350
TI  - Mitochondrial DNA rates and biogeography in European newts (genus Euproctus).
AB  - Sequence divergence for segments of three mitochondrial DNA (mtDNA) genes
      encoding the 12S and 16S ribosomal RNA and cytochrome b was examined in newts
      belonging to the genus Euproctus (E. asper, E. montanus, E. platycephalus) and in
      three other species belonging to the same family (Salamandridae), Triturus
      carnifex, T. vulgaris, and Pleurodeles waltl. The three Euproctus species occur
      (one species each) in Corsica, Sardinia, and the Pyrenees. This vicariant
      distribution is believed to have been determined by the disjunction and rotation
      of the Sardinia-Corsica microplate from the Pyreneean region. Because time
      estimates are available for the tectonic events that led to the separation of the
      three landmasses, we used sequence data to estimate rates of evolution for the
      three gene fragments and investigated whether they conform to the rate-constancy
      hypothesis. By the Tajima (1993, Genetics 135:599-607) test, we could not detect
      rate heterogeneities for the ribosomal genes and for transversions in the
      cytochrome b gene. Assuming that these sites are evolving linearly over time and
      that cessation of gene flow occurred simultaneously with vicariant events, we
      compared the time of divergence estimated by molecular distances with the
      divergence times based on the geological estimates. Because we have two estimates
      of divergence time from the geological record, the split of Corsica/Sardinia from
      the Pyrenees and the split of Corsica from Sardinia, we could compare ratios of
      molecular divergence with the ratio of geological time divergence. The ratios are
      very similar, indicating that the molecular clock hypothesis cannot be rejected.
      These geological events also allowed us to calculate absolute rates of evolution
      for ribosomal and cytochrome b genes and compare them to rates for the same
      regions in other salamandrids and other vertebrates. Ribosomal mtDNA rates are
      comparable to those reported for other vertebrates, but cytochrome b rates are 3
      7 times lower in salamanders than in other ectotherms. From a phylogenetic
      perspective, our data suggest that the cladogenic events leading to species
      formation in Euproctus and Triturus occurred very closely in time, indicating
      that the two genera may not be monophyletic. A duplication of the cytochrome b
      gene in T. carnifex was found, and the implications of this finding for mtDNA
      phylogenetic studies are discussed.

PMID- 11975351
TI  - Evolution of male tail development in rhabditid nematodes related to
      Caenorhabditis elegans.
AB  - The evolutionary pathway that has led to male tails of diverse morphology among
      species of the nematode family Rhabditidae was reconstructed. This family
      includes the well-studied model species Caenorhabditis elegans. By relating the
      steps of male tail morphological evolution to the phenotypic changes brought
      about by developmental mutations induced experimentally in C. elegans, the goal
      is to identify genes responsible for morphological evolution. The varying
      morphological characters of the male tails of several rhabiditid species have
      been described previously (Fitch and Emmons, 1995, Dev. Biol. 170:564-582). The
      developmental events preceding differentiation of the adult structures have also
      been analyzed; in many cases the origins of varying adult morphological
      characters were traced to differences during ontogeny. In the present work, the
      evolutionary changes producing these differences were reconstructed in the
      context of the four possible phylogenies supported independently by sequences of
      18S ribosomal RNA genes (rDNA). Two or more alternative states were defined for
      36 developmental and adult morphological characters. These characters alone do
      not provide sufficient data to resolve most species relationships; however, when
      combined with the rDNA characters, they provide stronger support for one of the
      four rDNA phylogenies. Assuming a model of ordered transformations for multistate
      developmental characters generally results in greater resolution. Transformations
      between character states can be assigned unequivocally by parsimony to
      unambiguous branches for most of the characters. Correlations are thereby
      revealed for some of the developmental characters, indicating a probability of a
      shared developmental or genetic regulatory pathway. Four of the unequivocal
      character state changes on unambiguously supported branches closely resemble the
      phenotypic changes brought about by known mutations in C. elegans. These
      mutations define genes that are known to act in genetic regulatory hierarchies
      controlling pattern formation, differentiation, and morphogenesis. Although these
      studies are still at an early stage, these results strongly suggest that parallel
      studies of developmental mutants in C. elegans and of morphological and
      developmental evolution among related nematodes will help define genetic changes
      underlying the evolution of form.

PMID- 11975352
TI  - Analyzing developmental sequences using sequence units.

PMID- 11975353
TI  - Searching for phylogenetic trees under the frequency parsimony criterion: an
      approximation using generalized parsimony.

PMID- 11975354
TI  - Is the Felsenstein zone a fly trap?
AB  - Although long-branch attraction, the incorrect grouping of long lineages in a
      phylogeny because of systematic error, has been identified as a potential source
      of error in phylogenetic analysis for almost two decades, no empirical examples
      of the phenomenon exist. Here, I outline several criteria for identifying long
      branch attraction and apply these criteria to 18S ribosomal DNA (rDNA) sequence
      data for 13 insects. Parsimony and minimum evolution with p distances group the
      two longest branches together (those leading to Strepsiptera and Diptera).
      Simulation studies show that the long branches are long enough to attract. When a
      tree is assumed in which Strepsiptera and Diptera are separated and many data
      sets are simulated for that tree (using the parameter estimates for that tree for
      the original data), parsimony analysis of the simulated data consistently groups
      Strepsiptera and Diptera. Analyses of the 18S rDNA sequences using methods that
      are less sensitive to the problem of long-branch attraction estimate trees in
      which the long branches are separate.

PMID- 11975355
TI  - The radiation of characiform fishes and the limits of resolution of mitochondrial
      ribosomal DNA sequences.
AB  - Phylogenetic relationships among fishes from ostariophysan orders, characiform
      families, and serrasalmin genera (e.g., "piranhas") were examined using partial
      mitochondrial ribosomal DNA sequences of the 12S and 16S genes. Phylogenetic
      information content of these sequences was assessed at three levels of taxonomic
      inclusiveness by analyzing the patterns of nucleotide substitution using
      secondary structure models. Conserved and variable regions were identified,
      mapped onto the structural models, and compared at increasing levels of taxonomic
      divergence. In general, loop regions (unpaired) exhibited a higher level of
      variation than did stem regions (paired). A high proportion of compensatory
      substitutions was observed in stem regions in three data sets, suggesting strong
      selection to maintain the secondary structure. Saturation due to multiple
      substitutions was indicated by decreasing transition/transversion ratios and
      strong structural constraints on variation in comparisons among orders of
      Ostariophysi but was not obvious among families of Characiformes and was not
      detected among serrasalmin genera. Reliable phylogenetic signal successfully
      reconstructed relationships among serrasalmin genera. However, aside from a few
      well-supported clades, relationships could not be reconstructed with confidence
      among characiform families and ostariophysan orders. The reciprocal monophyly of
      African and Neotropical characiform lineages was rejected (based on maximum
      likelihood ratio tests), and some support for previous hypotheses based on
      morphology was provided by the molecular data. The radiation of characiform
      fishes is discussed in a historical biogeographic context.

PMID- 11975356
TI  - Shared minds: rules of collaboration.

PMID- 11975357
TI  - Does virtual mean real or valid?

PMID- 11975358
TI  - Lawyers and the adversarial turn of mind.

PMID- 11975359
TI  - Monte Carlo methods for dose calculation and treatment planning: a revolution for
      radiotherapy.

PMID- 11975360
TI  - Download this!

PMID- 11975361
TI  - Bored dead meeting.

PMID- 11975362
TI  - Internet anatomy 101: knowing the turf you're going to surf.

PMID- 11975363
TI  - Community-based salt iodization program administered by hand sprayers: a trial in
      Mongolia since 1999.

PMID- 11975364
TI  - Palm oil: a healthful and cost-effective dietary component.
AB  - Palm oil is an excellent choice for food manufacturers because of its nutritional
      benefits and versatility. The oil is highly structured to contain predominantly
      oleic acid at the sn2-position in the major triacylglycerols to account for the
      beneficial effects described in numerous nutritional studies. Oil quality and
      nutritional benefits have been assured for the variety of foods that can be
      manufactured from the oil directly or from blends with other oils while remaining
      trans-free. The oxidative stability coupled with the cost-effectiveness is
      unparalleled among cholesterol-free oils, and these values can be extended to
      blends of polyunsaturated oils to provide long shelf-life. Presently the supply
      of genetic-modification-free palm oil is assured at economic prices, since the
      oil palm is a perennial crop with unparalleled productivity. Numerous studies
      have confirmed the nutritional value of palm oil as a result of the high
      monounsaturation at the crucial 2-position of the oil's triacylglycerols, making
      the oil as healthful as olive oil. It is now recognized that the contribution of
      dietary fats to blood lipids and cholesterol modulation is a consequence of the
      digestion, absorption, and metabolism of the fats. Lipolytic hydrolysis of palm
      oil glycerides containing predominantly oleic acid at the 2 position and palmitic
      and stearic acids at the 1 and 3 positions allows for the ready absorption of the
      2-monoacrylglycerols while the saturated free fatty acids remain poorly absorbed.
      Dietary palm oil in balanced diets generally reduced blood cholesterol, low
      density lipoprotein (LDL) cholesterol, and triglycerides while raising the high
      density lipoprotein (HDL) cholesterol. Improved lipoprotein(a) and apo-A1 levels
      were also demonstrated from palm oil diets; an important benefits also comes from
      the lowering of blood triglycerides (or reduced fat storage) as compared with
      those from polyunsaturated fat diets. Virgin palm oil also provides carotenes
      apart from tocotrienols and tocopherols that have been shown to be powerful
      antioxidants and potential mediators of cellular functions. These compounds can
      be antithrombotic, cause an increase of the prostacyclin/thromboxane ratio,
      reduce restenosis, and inhibit HMG-CoA-reductase (thus reducing) cholesterol
      biosynthesis). Red palm oil is a rich source of beta-carotene as well as of alpha
      tocopherol and tocotrienols.

PMID- 11975365
TI  - Regional study of nutritional status of urban primary schoolchildren. 1. Manila,
      Philippines.
AB  - This multicity study sought to provide baseline information on the nutritional
      status of urban schoolchildren in order to examine the emerging problem of
      overweight and obesity in this age group. The study included 1,208 children 8 to
      10 years old who were randomly selected from all public and private schools in
      Manila for weight and height measurements. Nutritional status was assessed by
      weight-for-age and height-for-age Z scores and BMI percentile cutoff points. On
      the average, private schoolchildren were taller and heavier and had higher body
      mass index (BMI) values than public schoolchildren, resulting in a much lower
      prevalence of undernutrition and a much higher prevalence of overnutrition. These
      results have important programmatic implications. However, using the World Health
      Organization (WHO)--recommended cutoff points to define under- and overnutrition
      gave contrasting results when weight-for-height and BMI were used. There appears
      to be a need to validate the anthropometric reference standards and cutoff points
      in children and adolescents to better define nutritional status and ascertain the
      influence of ethnicity.

PMID- 11975366
TI  - Nuclear and isotopic techniques for addressing nutritional problems, with special
      reference to current applications in developing countries.
AB  - Nuclear and isotopic techniques are valuable tools in human nutritional research
      studies. Isotopes, both radioactive and nonradioactive, enable detailed
      evaluations of nutrient intake, body composition, energy expenditure, status of
      micronutrients, and nutrient bioavailability. In recent times, isotopic methods
      have been widely used in a number of coordinated research projects and technical
      cooperation projects of the International Atomic Energy Agency's Nutrition
      Programme. The doubly labeled water technique combines the use of the stable
      isotopes oxygen-18 and hydrogen-2 (deuterium) to measure total energy expenditure
      in free-living human subjects, and to investigate the magnitude and causes of
      both undernutrition and the emergence of obesity in developing countries. The
      deuterium dilution technique is a reliable tool to measure breastmilk intake and
      thereby infant growth and development. In collaboration with the World Health
      Organization's Growth Monitoring Program, this technique is being used to
      generate new data on growth standards for children in developing countries. This
      technique is also used in the measurement of body composition by the estimation
      of lean body mass and fat mass in individuals. Stable isotopes of iron and zinc
      have been successfully used to assess the nutritional impact of several
      nationwide food supplementation-programs conducted on pregnant and lactating
      women and children in both industrialized and developing countries. Isotopic
      techniques are especially suitable for monitoring changes in body composition,
      energy metabolism, and mineral status (with particular reference to osteoporosis)
      in the elderly. Nuclear methods have also served to develop models for a
      physiological reference man in Asia in support of radiological health and safety
      issues, for establishing elemental composition of foods, and for measurement of
      pollutants in the environment.

PMID- 11975367
TI  - Regional study of nutritional status of urban primary schoolchildren. 2. West
      Jakarta and Bogor, Indonesia.
AB  - The study provides information on the nutritional status of 8- to 10-year-old
      primary schoolchildren in urban areas of Jakarta and Bogor, Indonesia, based on
      anthropometric indicators. It compares the use of the anthropometric indicators
      weight-for-age Z score, height-for-age Z score, weight-for-height Z score, and
      body mass index (BMI) to assess thinness (underweight and wasted) and overweight
      in children. A total of 1,367 children were examined. The nutritional status of
      the 8- to 10-year urban schoolchildren was better than that of urban children
      under 5 years old. The prevalence of underweight among urban schoolchildren
      ranged from 7.4% (girls) to 12.95% (boys), while underweight among urban children
      under 5 years old in 1998 was 29.7%. Meanwhile, the prevalence of overweight (BMI
      > 85th percentile) ranged from 15.3% (girls) to 17.8% (boys). There were more
      overweight children in the private schools than in the public schools. On
      average, private schoolchildren, of all ages and both sexes, were heavier and
      taller than public schoolchildren. The BMI indicator for "thinness" and
      "wasting", using the NHANES reference, indicates a false positive result. For
      detecting overweight in children aged 8 to 10 years, BMI is comparable to the
      other indices, weight-for-age, height-for-age, and weight-for-height.

PMID- 11975368
TI  - Regional study of nutritional status of urban primary schoolchildren. 3. Kuala
      Lumpur, Malaysia.
AB  - A total of 5,995 (7.8% of all 7- to 10-year-old primary schoolchildren in Kuala
      Lumpur), randomly selected from 166 schools (97.6% of all schools), were measured
      for their weight and height. The analyses of all weight and height data,
      including the cutoffs used for defining stunting, underweight, and wasting and
      for thinness and overweight, were carried out as recommended by the World Health
      Organization (WHO). The prevalances of stunting (height-for-age Z score < -2 SD),
      underweight (weight-for-age Z score < -2 SD) and wasting (weight-for-height Z
      score < -2 SD) among all the children studies were 6.7%, 7.1%, and 4.5%,
      respectively. Undernutrition among boys was more serious than among girls
      according to all three indicators. Because it was not possible to analyze the
      weight-for-height data for most of the children above 8.5 years of age, body mass
      index (BMI)-for-age was used to determine the prevalences of thinness and
      overweight for all the children. Based on the reference data, the prevalence of
      overweight (at or above the 95th percentile) was 9.7% and 7.1% for boys and
      girls, respectively, and 8.4% overall.

PMID- 11975369
TI  - Do street food vendors sell a sufficient variety of foods for a healthful diet?
      The case of Nairobi.
AB  - This study examined whether street food vendors sell a sufficient variety of
      foods for a healthful diet. It was hypothesized that vendors sold only low-cost
      food groups to enable the buyer to afford the food while the vendor also made a
      profit. A structured questionnaire was administered to 580 vendors in three
      selected locations. Data included product names, ingredients, methods of
      preparation, and the sex of the vendor. A little more than half of the vendors
      (53%) sold food of only one group; 44% sold cereals. Overall, 36% of vendors,
      mostly men, sold only carbohydrate products. The percentage of vendors selling
      foods of more than one group was higher in the working area (53%) than in the
      slum area (43%, p < .05), and it was higher in both of these areas taken together
      than in the lower-middle income area (21%, p < .001). Micronutrient and mixed
      nutrient products were associated with female vendors. Although a slight majority
      of all street vendors sell foods of only one group, women vendors are capable of
      supplying a sufficient variety of food groups that consumers can afford. It
      appears that consumer purchasing power dictates the food groups provided by
      vendors, especially cereal-based-foods. A policy on micronutrient fortification
      of cereal flours and fats used in popular street food preparation needs to be
      considered. This could be coupled with consumer and vendor education programs
      focusing on the importance of healthful diets.

PMID- 11975370
TI  - Iron and energy supplementation improves the physical work capacity of female
      college students.
AB  - A nutritionally controlled study was conducted on two groups of 15 female college
      students aged 16 to 20 years, selected from Punjab Agricultural University,
      Ludhiana, Punjab, India. The girls were either anemic (hemoglobin 7.7 g/dl) but
      energy adequate (AEA), or anemic (hemoglobin 7.4 g/dl) and energy deficient
      (AED). The AEA group was given iron supplementation (60 mg iron/day) for 6 to 9
      months along with 100 mg of ascorbic acid, and the AED group was given iron as
      well as energy supplementation for 3 months. There was a significant (p < .01)
      increase in weight, body mass index, mid-upper-arm circumference, and body fat in
      the AED group after iron-energy supplementation. Hemoglobin, serum iron,
      transferrin saturation, total iron-binding capacity, and unsaturated iron-binding
      capacity were below normal in both groups; however, after iron and iron-energy
      supplementation, there was a significant (p < .01) increase, and these indices
      were in the normal range. There was a significant (p < .01) increase in exercise
      time and maximum work load tolerance after iron and iron-energy supplementation.
      Combined energy and iron deficiency had a greater adverse effect on physical work
      capacity than energy or iron deficiency alone.

PMID- 11975372
TI  - Development and validation of a short food-frequency questionnaire for screening
      women of childbearing age for vitamin A status in northwestern Iran.
AB  - A high percentage of women in their childbearing years suffer from subclinical
      vitamin A deficiency; 10% to 20% of pregnant women worldwide are vitamin A
      deficient. This study aimed to design and validate a short food-frequency
      questionnaire to serve as a simple screening tool for vitamin A status in women
      of childbearing age. The sample consisted of 187 healthy, nonpregnant,
      nonlactating women 15 to 49 years of age, from urban and rural areas of Marand
      district in East Azerbaijan. Dietary intake was evaluated by a face-to-face
      interview using a 24-hour dietary recall for two consecutive days and a 41-item
      qualitative food frequency questionnaire. Height, weight, and serum retinol were
      measured. Serum retinol values were less than 20 micrograms/dl for three
      subjects, while an additional 34 subjects (18%) had values between 21 and 30
      micrograms/dl. Principal-component analysis performed on the food-frequency
      questionnaire identified five components that together defined 34.4% of the
      variance in estimated vitamin A intake and were used to derive a 20-item short
      food-frequency questionnaire. Internal consistency of the short instrument was
      acceptable (Cronbach's alpha = .59). Serum retinol was significantly correlated
      with total vitamin A intake and with intake of vitamin A from plant sources, as
      estimated by the short food-frequency questionnaire. Important sources of
      provitamin A in these women's diets included some not typical of other
      populations: nuts and green leaves of types used elsewhere in small quantities as
      herbs, but important in Iran because the amount and frequency of consumption are
      relatively high. We conclude that the questionnaire is relatively valid and
      potentially useful in identifying women at risk for vitamin A deficiency in this
      population.

PMID- 11975371
TI  - Toward better compliance with iron-folic acid supplements: understanding the
      behavior of poor urban pregnant women through ethnographic decision models in
      Vadodara, India.
AB  - This study made an attempt to develop ethnographic decision models to understand
      and improve iron-folic acid supplement procurement and compliance-related
      behaviors of poor urban pregnant women in Vadodara, India, based on data obtained
      through the use of qualitative research tools. Open-ended, in-depth interviews
      were conducted with 36 pregnant women (17-32 weeks of gestation) purposively
      selected from four urban slums. Fortnightly home visits were made to the houses
      of 20 pregnant women-family member pairs to elicit behaviors related to iron
      folic acid supplement procurement and compliance at the household level, from
      which the ethnographic decision models were developed. The hemoglobin levels of
      these women were also assessed. Regular counseling until delivery, based on the
      ethnographic data, helped to improve compliance, which resulted in 95% of the
      women consuming over 90% of the required dose. The mean hemoglobin level also
      improved from 9.6 to 11.08 g/dl until the end of the last trimester. This study
      highlighted the need for qualitative ethnographic data to develop such models
      that would help in the understanding of specific behaviors that influence program
      acceptance. Such data would have policy-level implications, for example,
      developing appropriate information-education-communication material and
      counseling strategies.

PMID- 11975373
TI  - Factors associated with successful pregnancy outcomes in upper Egypt: a positive
      deviance inquiry.
AB  - A positive deviance inquiry was conducted in Al-Minia, Upper Egypt, to identify
      factors associated with achievement of good pregnancy outcomes despite limited
      resources. As compared with women with poor weight gain (n = 30), low-income
      women with weight gain greater than 1.5 kg per month in the second trimester of
      pregnancy (n = 11) were more likely to report multiple antenatal care contacts
      (80% versus 43%), increased rest during pregnancy (67% versus 7%), and more
      consumption of meat (33% versus 13%) and vegetables (82% versus 37%), and were
      less likely to report symptoms consistent with urinary tract infection (50%
      versus 90% with dysuria and 0% versus 57% with cloudy or reddish urine). Similar
      characteristics distinguished low-income women in a more economically advantaged
      community whose newborns weighed more than 3 kg (n = 18) as compared with mothers
      of smaller newborns (n = 18). These characteristics were similar to those
      identified in the National Research Center's Al-Minia birthweight study. The
      positive deviance inquiry is an affordable, participatory step to identify
      accessible individuals, behaviors, and conditions for improved perinatal health.

PMID- 11975374
TI  - Difference in goiter rates between regular and occasional users of iodized salt
      in Mongolia.
AB  - In Mongolia many households use iodized salt only occasionally. We investigated
      whether the occasional use of iodized salt had an impact on the reduction of
      goiter size. We examined 685 children (8-11 years old) in five groups of
      households that (1) used iodized salt regularly, (2) used more than 10 kg of
      iodized salt annually, (3) used 6 to 10 kg annually, (4) used less than 6 kg
      annually, (5) and regularly used noniodized salt. The prevalence of goiter as
      determined by ultrasound in these five groups was 31.1%, 30.3%, 40.6%, 52.1%,
      56.6%, respectively. There was no difference between goiter rates among the first
      three groups, but these groups had significantly lower rates than the last two
      groups. We concluded that annual use of more than 6 kg of iodized salt,
      preferably more than 10 kg, by a household had a beneficial effect on the rate of
      goiter. In addition, the possibility was suggested that households that consumed
      only iodized salt consumed less salt than other households.

PMID- 11975375
TI  - Iron-deficiency anemia in young working women can be reduced by increasing the
      consumption of cereal-based fermented foods or gooseberry juice at the workplace.
AB  - This efficacy for both employers and employees (young working women 18 to 23
      years of age) was undertaken to determine whether culturally acceptable dietary
      changes in lunches in the workplace and at home could bring about a behavioral
      change and improvement in their iron-deficiency anemia status. Maximum weight was
      given to increasing consumption of iddli, a popular cereal-based-fermented food,
      or of gooseberry juice. Four small factories were selected in periurban
      Bangalore, with a sample of 302 women. The 180-day interventions were supervised
      at the workplace. In unit 1 (72 women), the intervention consisted of iddli four
      times a week plus information, education, and communication (IEC) related to iron
      deficiency anemia. Unit 2 (80 women) received 20 ml of gooseberry juice
      (containing 40 mg of vitamin C) three times a week plus IEC once a month. Women
      in unit 3 (70 women), the positive control, received 400 mg albendazole once plus
      ferrous sulfate tablets (60 mg elemental iron) two times a week. No IEC was
      given. Unit 4 (70 women) served as the negative control and received no
      intervention. The pre-post impact measures were dietary and nutrient intake,
      knowledge and practice, and hemoglobin status. In units 1, 2, and 3, the
      hemoglobin status of the women improved significantly from 11.10 to 12.30 g/dl,
      11.20 to 12.70 g/dl, and 11.50 to 13.00 g/dl, respectively. In unit 4 there was
      no change: the values were 10.90 g/dl before and after intervention. The results
      show that the type of workplace lunch was of greater significance than IEC.
      Knowledge gains were impressive, but behavioral change was not sustained. It was
      concluded that the hemoglobin levels of the workers can easily be improved by
      cost-effective workplace lunches that also lead to better employer-employee
      relations.

PMID- 11975376
TI  - The rhetoric of psychological research and the problem of unification in
      psychology.
AB  - There has been in the field of psychology a long and well-documented discontent
      with an apparent disorganization in its literature, most often interpreted as
      reflecting the absence of a unifying theory. This article examines some
      alternative ways in which some of the disorganization is being actively created
      by forms of argumentation used in reporting and discussing psychological
      research. One institutionalized form of argumentation used in reporting data
      actually generates the proliferation of theoretical terms in the literature. A
      second form of argumentation reifies theories into social groups, incorporating
      values that discourage theoretical integration. Some of the discontent arises
      from the incompatibility between the values latent in such social organizations
      and the values that motivate scientific inquiry at a personal level.

PMID- 11975377
TI  - Genetic testing and psychology. New roles, new responsibilities.
AB  - Advances in genetics and genetic testing promise to catalyze a fundamental change
      in the practice of medicine. Psychologists have much to offer as
      psychotherapists, researchers, educators, and policymakers to a society heavily
      influenced by the genetic revolution. To make the most of new opportunities
      available to mental health professionals in genetics, psychologists must know
      basic genetic principles and learn what is new about 21st-century genetics. The
      core competencies for all health professionals developed by the National
      Coalition for Health Professional Education in Genetics are related in this
      article to the significant roles psychologists can play in helping individuals
      with genetic concerns to cope with vulnerability, optimize family interaction,
      and improve health behaviors.

PMID- 11975378
TI  - Ernest R. Hilgard (1904-2001).

PMID- 11975379
TI  - The emperor's new clothes: sociopolitical diversity in psychology.

PMID- 11975380
TI  - Diversity American style.

PMID- 11975381
TI  - In the right direction but slightly off course.

PMID- 11975382
TI  - A biased view of liberal bias.

PMID- 11975383
TI  - Examining Redding's (2001) claims about lesbian and gay parenting.

PMID- 11975384
TI  - Can pluralism be intolerant?

PMID- 11975385
TI  - Grappling with diverse conceptions of diversity.

PMID- 11975386
TI  - Achieving diversity: hidden assumptions.

PMID- 11975387
TI  - High stakes are an opportunity.

PMID- 11975388
TI  - A remedy for the black-white test-score disparity.

PMID- 11975389
TI  - No easy solution to subgroup differences.

PMID- 11975390
TI  - [Requirements of clinical excellence].
AB  - The history of the evidence based medicine, health technology assessment, health
      economics and quality improvement proved to be a success story in developed
      countries. It is partly due to that change in the attitude towards health care
      occurred in the past ten or fifteen years. Two major factors played important
      roles in this process. On the one hand, the booming health care costs in
      developed countries, and on the other, the health benefit was not proportional to
      costs. First, governments around the world applied the tool of cutting costs,
      which proved to be uneffective even in mid-term. It was soon revealed that people
      prefer good-quality health care rather than the cheap one. These disciplines are
      having a more and more considerable influence on medical care and nursing.
      However, impacts on health care are not automatic and can be most different
      regarding both their quantity and nature. They may result in a significant
      improvement in prevention, diagnostics, cure and care, and may yield a more
      appropriate use of ever-limited resources.

PMID- 11975391
TI  - [Clinical aspects of Epstein-Barr-virus-associated lymphoproliferative disease].
AB  - Majority of the Western population is infected with the Epstein-Barr virus.
      Except for mononucleosis accumulating in adolescents, the infection occurs in a
      rather symptomless manner. But later on under special circumstances the virus may
      play an important role, again. As a result of long-lasting and intensive
      immunosuppression i.e. following transplantation a lymphoproliferation of B cell
      origin may develop in some patients. The biologic behaviour is often more
      aggressive than expected by the histological occurrence. Early identification of
      predisposed patients is an important but difficult task: the disease exhibits a
      rather heterogeneous phenotype and the grading is problematic by the standard
      classification criteria of non-Hodgkin malignant lymphomas. Nevertheless the
      diagnosis and the therapy based on the appropriate pathomechanism can increase
      the chances of convalescence. This review article discusses the pathomechanism,
      diagnostic and therapeutic relevance of the posttransplant lymphoproliferative
      disease.

PMID- 11975392
TI  - [Results of mammographic screening at the Mammary Center of Debrecen in 1999 and
      2000].
AB  - INTRODUCTION: The screening mammography decreases the mortality of female breast
      cancer. METHODS: A complex, independent centre of screening mammography has been
      operating in Debrecen since 1999. RESULTS: The number of the examinations were
      10,399 in 1999 and 13,800 in 2000. The number of explored breast cancer cases
      were 43 (0.41%) in 1999 and 62 (0.45%) in 2000. CONCLUSION: Although the
      mortality reduction can be exactly measured after several years, we are convinced
      that the chances for a better life of these 107 women operated on with breast
      cancer in early state increased thanks to our project. The results of the breast
      cancer screening program in Debrecen fulfilled the professional requirements of
      mammographic service-screening.

PMID- 11975393
TI  - [Current trends in pharmacotherapy of breast cancer].
AB  - INTRODUCTION: Breast cancer is a systemic disease, unfortunately clinically
      undetectable micrometastases are present in many women even in early stages of
      the disease. Many of these patients can be cured with combined modality treatment
      of surgery, radiation and chemo- or hormone therapy. AIM: To survey the treatment
      of breast cancer. METHOD: The author presents an overview of the treatment of
      breast cancer based on the relevant literature and experience. RESULTS: Systemic
      adjuvant treatments include cytotoxic and hormone therapy. The most commonly used
      cytotoxic agents are cyclophosphamide, methotrexate, 5-fluorouracil, doxorubicin
      and epirubicin. The anthracycline-containing regimens are slightly superior, and
      the addition of taxane to an anthracycline-containing regimen may further
      increase the efficacy of adjuvant chemotherapy. Patients with metastatic disease
      cannot be cured, the goal of the treatment is to improve quality of life, and
      prolong survival. Up to 60-80% of these patients may experience objective tumor
      response to first-line combination chemotherapy. The taxanes (paclitaxel or
      docetaxel) with anthracyclines are the most active chemotherapy drugs against
      breast cancer. The best results are achieved with second-, third-line
      chemotherapy drugs: capecitabine, vinorelbine, gemcitabine, 5-fluorouracil and a
      variety of its oral pro-drugs. The most recent developments are represented by
      the biologically-targeted drugs, the first agent developed trastuzumab, has
      already been introduced in the clinic. The combination of chemotherapy with
      various response modifiers is a rapidly developing field of clinical cancer
      research. Several other new agents including growth factor receptor antagonists,
      tumor vaccines, antiangiogenic agents are tested in clinical trials alone and in
      combination with chemotherapy. CONCLUSIONS: The combination of chemotherapy with
      the new generation of drugs is a rapidly advancing and important field of
      clinical oncology.

PMID- 11975395
TI  - [Armenian physicians in Hungarian medicine].

PMID- 11975394
TI  - [Swedish exercise therapy in Hungary in the middle of the 19th century--Per
      Henrik Ling (1776-1839)].

PMID- 11975396
TI  - [Renal failure].

PMID- 11975397
TI  - [Chronic renal failure: when do patients need a nephrologist?].
AB  - Renal insufficiency is a fairly frequent problem, whether it is due to a kidney
      disease per se or to an extrarenal disease or to a combination of both. In
      contrast, chronic renal failure requiring renal replacement therapy is a rare
      condition in the practitioner's office. Considering this, the question is
      important to the practitioner, when in the course of the disease there is need
      for referral to a nephrologist. In this context two main questions have to be
      raised: first, is the disease curable or at least partially reversible (depending
      on the etiology of the renal disease) and second, when has the time arrived to
      prepare the patient for a renal replacement therapy. The cooperation with a
      nephrologist has to be sought early enough in order to choose the best moment for
      these actions. There are several European and American studies dealing with these
      problems and proving the benefit of a timely referral and a timely start of
      treatment. We extract some of the relevant data considering own data collected at
      the University Hospital of Berne (Inselspital), Switzerland.

PMID- 11975398
TI  - [Renal biopsy: standard procedure of modern nephrology].
AB  - For more than 50 years, renal biopsy has been an important diagnostic procedure
      in modern nephrology. Increasing perfection of the biopsy technique has made the
      procedure very safe, with rare complications and few contraindications. Improved
      histological diagnostics and broader therapeutic possibilities have significantly
      expanded the indications. The most important indications are acute renal failure,
      proteinuria > 1 g/d (or 3 g/d) and nephritic urinary sediment. Complications with
      renal grafts provide additional indications for a renal biopsy. In addition,
      diabetes and monosymptomatic urinfindings (isolated haematuria) as well as
      pregnancy induced nephropathy are indications for a renal biopsy. The procedure
      is performed ambulatory or during a short hospital stay and the patient can
      usually be discharged after a monitoring period of eight hours.

PMID- 11975399
TI  - [Supportive medical management of patients with chronic renal failure].
AB  - Progressive renal failure occurs in a large number of patients even in the
      absence of the original cause of injury. It is suggested that the initial
      reduction in nephron number progressively damages the remaining ones. Various
      mechanisms underlie the pathogenesis of progressive glomerular injury. Several
      studies have extensively shown that both dietary protein restriction and
      pharmacologic intervention with ACE-inhibitiors and angiotensin receptor
      antagonists effectively slow the progression of chronic renal diseases. This
      article will present treatment recommendations designed to delay the progression
      of chronic renal disease, to optimize its medical management and to reduce
      complications induced by renal insufficiency including hypertension, renal
      osteodystrophy and anemia. Ten steps in the management of patients with chronic
      renal failure recommended by an international panel of experts based on existing
      guidelines are presented.

PMID- 11975400
TI  - [Adverse renal effects of legal and illicit drugs].
AB  - The most important task of clinical and experimental nephrology is to identify
      risk factors for progression of renal failure with the ultimate goal to
      counteract the dramatic increase of patients reaching end-stage renal disease.
      Recently, cigarette smoking has been recognized to be one of the most important
      remediable renal risk factors. The adverse renal effects of smoking seem to be
      independent of the underlying renal disease and the current evidence suggests a
      near doubling of the rate of progression in smokers vs. non-smokers. Cessation of
      smoking slows the rate of progression. Besides smoking, alcohol abuse has also
      been implicated as a renal risk factor. The present article reviews the current
      knowledge about the adverse renal effects of these legal drugs. Furthermore, the
      acute and chronic renal complications due to illegal recreational drugs is
      discussed. The impact of these drugs on the risk to reach end-stage renal failure
      is difficult to assess, which is mainly due to the fact that it is difficult to
      perform controlled prospective studies in substance abusers. According to
      estimates, 5-6% of new patients starting end-stage renal disease therapy may have
      opiate-use-related renal diseases in the USA--a figure which documents the
      magnitude of the problem. Thus, in any case of unexplained renal functional
      impairment substance abuse should be considered by the physician.

PMID- 11975402
TI  - [Vesico-ureteral reflux, reflux nephropathy and terminal renal failure].
AB  - Vesicoureteric reflux is subcategorized into primary and secondary. Secondary
      vesicoureteric reflux results from increased bladder pressure duo to anatomic
      outlet obstruction or neuropathic disturbances. Primary vesicoureteric reflux was
      felt to result from a congenitally short mucosal tunnel length but this concept
      has been thrown into question. Recent studies suggest an association between
      lower urinary tract dysfunction and primary vesicoureteric reflux. Primary
      vesicoureteric reflux is often associated with kidney damage. It has been
      traditionally assumed that in children with primary vesicoureteric reflux kidney
      damage results from reflux of infected urine into the renal tissue. While there
      is unarguable proof that kidney damage can be acquired by the reflux of infected
      urine, the extent of reflux nephropathy explained by this mechanism has been
      overemphasized. Recent observations indicate that there are two categories of
      primary reflux disorder: a mild reflux associated with an acquired renal scarring
      secondary to infections which affects most females and a proportion of males; and
      a prenatal high-grade vesicoureteric reflux with a congenital nephropathy
      characterized by generalized hypodysplastic features which almost exclusively
      affects boys. Treatment options of primary vesicoureteric reflux range from
      surgical ureteric reimplantation to antimicrobial prophylaxis. Findings from
      comparative trials of prophylactic antibiotics and surgical management of
      children with high-grade vesicoureteric reflux do not show difference in renal
      growth and acquisition of new scars or renal function for 10 years. The factors
      accounting for the outcome in the mentioned studies are that most damage occurs
      at a very early stage and that severely damaged kidneys will either remain stable
      or progress to end-stage kidney disease, despite all efforts to cure the reflux.

PMID- 11975401
TI  - [Renal involvement in malignant tumors].
AB  - Malignant tumors may affect the kidney in a direct and in an indirect fashion. In
      addition, there are multiple paraneoplastic syndromes and the side effects of the
      tumor therapy. Therefore, clinicians may encounter a wide spectrum of disorders
      representing almost all aspects of kidney diseases. Importantly, practitioners
      taking care of patients with glomerulopathies must always consider the
      possibility of a co-existence of a malignancy, as highlighted by our case report.

PMID- 11975403
TI  - [A rare cause of nephrotic syndrome in a young woman with flank pain, milky urine
      and leukocyturia].
AB  - A 27 year old patient presented with a sudden acute illness showing right flank
      pain, milky urine, nephrotic range proteinuria, erythrocyturia and leukocyturia
      in the urinary sediment with a negative leukocyte test stick. The proof of a
      pronounced hypertriglyceriduria led to the diagnosis of Chyluria. The
      lymphangiogram confirmed the presence of a retroperitoneal lymphatic dysplasia
      with evidence of communication with the right renal pelvis on the CT-lymphogram.
      Chyluria is generally the result of parasitic infection and is extremely rare in
      Europe. In the presence of symptoms including milky urine, proteinuria and
      leukocyturia in the urinary sediment and a negative urine leukocyte stick test
      and absence of infectious signs, chyluria must be suspected. The diagnosis should
      be substantiated through proof of hypertriglyceriduria and confirmed by
      lymphangiography.

PMID- 11975404
TI  - ["Integrated treatment of rectal cancer"].

PMID- 11975406
TI  - [Adjuvant radiotherapy in rectal cancer and total mesorectal excision].
AB  - Local recurrence (LR) after surgical resection for adenocarcinoma of the rectum
      still remains an unsolved problem. Local relapse often occurs when tumor spreads
      in perirectal fat (mesorectum) or along the lateral iliac lymph nodes also when
      surgery is considered radically. There is a close relationship between local
      recurrence rate and lymphatic involvement, local tumor extension and tumour
      grading. Total mesorectal excision (TME) appears to be associated with a reduced
      LR rate when resection of perirectal fat is done "en-bloc" and when a negative
      radial margins is obtained. TME allows autonomic nerve sparing and sphincter
      preservation too, but lateral nodes are not treated by TME. Extended
      lymphadenectomy with lateral dissection for advanced rectal cancer has been often
      associated with an increase rate of long term morbidity, particularly regarding
      urinary and sexual function. Concomitant preoperative chemo-radiation for
      advanced rectal cancer is a relatively safe procedure with an acceptable
      morbidity and mortality. This approach is associated with a considerable clinical
      and pathologic tumor downstaging. Tumor resectability is improved and lateral
      spreading is also better controlled. An improving in survival and a longer
      disease free period has been reported. More radical sphincter saving operations
      are also allowed.

PMID- 11975405
TI  - Present indications for adjuvant therapy in resectable rectal cancer.
AB  - Combined modality therapy is an effective adjuvant therapy for many patients with
      clinically resectable rectal cancer. The indications for adjuvant therapy for
      rectal cancer are based on the pattern of failure after surgery. Despite radical
      surgery, local-regional failure frequently occurs in patients with transmural or
      node-positive rectal cancers. The incidence of treatment failure in the pelvis is
      directly correlated with the extent of transmural penetration (microscopic vs
      gross) and the additional risk of lymph node metastases. In the post-operative
      setting its use is dictated by pathologic stage and the type of operation (i.e.
      conventional surgery or a local excision). The choice of which post-operative
      adjuvant regimen to recommend in the non-protocol setting remains controversial.
      If 5-FU alone is used, then it is best administered by continuous infusion. In
      the preoperative setting, the use of adjuvant therapy depends on the clinical
      stage and the need for sphincter preservation. Phase I/II trials examining the
      use of newer chemotherapeutic agents such as Tomudex, UFT/leucovorin, CPT-11,
      oxaliplatin, eniluracil and capecitabine with preoperative radiation therapy are
      in progress. This review examines both the selection criteria and results of
      adjuvant combined modality therapy for patients with clinically resectable rectal
      cancer.

PMID- 11975407
TI  - Low dose preoperative radiation in the treatment of carcinoma of the rectum.
AB  - Recent advances in the treatment of cancer of the rectum show a steady
      improvement in survival. Newer surgical techniques and expanding options for
      adjunctive therapy appear to have had a significant impact on improving both
      local control and distant disease. Five-year survival of patients now ranges from
      85-90% for stage I cancers and 50-55% for stage III cancers. Local recurrence of
      disease following curative surgical resections is dependent on the stage of the
      tumor and for some high-risk patients, stages T3/T4 and N+ disease, has been
      reported as high as 40-60%. In an attempt to lower the rate of local recurrence
      and improve survival, several approaches to adjuvant therapy have been utilized.
      Preoperative radiation was one approach that has been used extensively in the
      last decades. Recently, the large Swedish randomized studies using a short course
      (5 Gy x 5) of preoperative radiation have reported a clear improvement in local
      control and survival of patients. These results were achieved with no downstaging
      of disease since surgery was performed put immediately after irradiation.
      Therefore it should be presumed that preoperative radiation therapy resulted in
      the sterilization of tumor cells, which prevented both local and distant
      dissemination leading to the improved outcome. The question remains, therefore,
      as to what is the least and/or the most appropriate dose of preoperative
      irradiation that can achieve the beneficial effect of minimizing tumor cell
      dissemination at surgery. Low dose preoperative irradiation as a single fraction
      of 500 cGy appears to have a sound biological basis and in single institutional
      studies it was shown to be effective but in randomized studies it did not improve
      results. This is likely to be due to a poor design of trials and/or inappropriate
      patient selection for these studies. A well-designed study still remains to be
      done.

PMID- 11975408
TI  - Preoperative radiotherapy for rectal cancer: hypofractionation with multiple
      fractions (15-25 Gy).
AB  - Preoperative radiotherapy lowers local recurrence rates after rectal cancer
      surgery, as seen in several randomised trials. Postoperative radiotherapy is also
      effective, although a higher radiation dose is required. In addition,
      preoperative, but not postoperative (unless combined with chemotherapy)
      radiotherapy also improves survival slightly. Since the toxicity profile also
      favours preoperative therapy, this is a more attractive approach. The trials have
      also shown that a sufficiently high biological dose is required to achieve any
      influence on local failure rates. If the dose at each radiation fraction is
      higher (e.g. 5 Gy), the radiation can be given much faster (during one week) than
      if a 'conventional' fraction size of about 2 Gy is used (4-5 weeks). Surgery can
      also safely be performed immediately after the end of the short radiation course,
      but not until several weeks later after conventional radiotherapy. This adds to
      the practicability of the short schedules. An inappropriate radiation technique
      was used particularly in one trial using multiple 5 Gy fractions. This resulted
      in unacceptable acute and late toxicity. However, several other trials have shown
      that the treatment is safe. Preoperative 5 x 5 Gy is one of the most extensively
      investigated oncological treatments with proven efficacy. Since the total dose is
      comparably low (25 Gy), the decreased therapeutic ratio of using fraction sizes
      above 2 Gy appears to have no clinical relevance. The experience indicates,
      however, that every therapeutic modality should be used in an optimal way.

PMID- 11975409
TI  - [Preoperative radiotherapy in rectal cancer: conventional fractionation].
AB  - Experiences on preoperative radiation therapy with conventional fractionation for
      rectal cancer are reviewed. Results in terms of local control, survival and
      sphincter preservation are focused in resectable disease; the impact on
      resectability, local control and survival are analysed in unresectable disease.
      Randomized trials reported in the 80s, demonstrated a significant impact on local
      control with a pre-op dose of 34.5-40 Gy vs surgery alone. An increased risk of
      complications was reported because of the suboptimal treatment techniques used.
      No increase in operative mortality was noted and no impact on survival was
      reported. Recent non-randomized trials demonstrated more acceptable toxicity with
      appropriated treatment techniques. Doses of 45-50.4 Gy allowed an high clinical
      remission rate and downstaging at surgery. A longer interval between radiation
      therapy and surgery (4-6 weeks) influenced these results and about 75% of
      patients, who were declared to need an abdominoperineal resection at diagnosis,
      underwent conservative surgery. Retrospective studies in unresectable disease
      reported a resectability rate of 39.64% after 45-60 Gy of pre-op radiation
      therapy. Surgical resection demonstrated an impact on survival in most of these
      patient series. In conclusion, preoperative radiation therapy with conventional
      fractionation allows downstaging of initial disease with possible impact on local
      control, sphincter preservation in resectable disease and surgical resection in
      unresectable disease.

PMID- 11975410
TI  - [Simultaneous radiochemotherapy in rectal tumors].
AB  - After about 30 years from the first trials on concurrent chemoradiation in the
      treatment of rectal carcinoma, a large experience in this field has been shared,
      both in terms of laboratory and clinical data. The possibility of concurrent
      chemoradiation to improve the clinical outcome and sphincter preservation in low
      rectal tumors has been extensively demonstrated. Great attention should be paid
      to the quality of radiation treatment and drug administration, to minimize the
      risk of therapy-related toxicity. The impact of preoperative chemoradiation on
      tumor control will be further clarified by the ongoing randomized studies, in
      terms of comparison with radiation therapy alone (EORTC study), "Total mesorectal
      excision" (Duch Study), postoperative chemoradiation (German CAO/ARO/AIO 94) and
      the potential role of adjuvant chemotherapy (EORTC and Italian study). A series
      of phase II studies will probably clarify the role of unconventional
      fractionation modalities (hyperfractionation, accelerated treatments) and of new
      concomitant chemotherapy (new drugs, chronomodulation) in terms of organ and
      sphincter preservation. A close cooperation between radiation oncologists,
      medical oncologists and surgeons is required.

PMID- 11975411
TI  - [Intraoperative radiotherapy (IORT) in the treatment of rectal cancer].
AB  - BACKGROUND: Local recurrence remains one of the most complex problem in the
      management of rectal carcinoma. Often, surgery alone is not able to prevent local
      recurrence development, particularly in locally advanced cancer. A better local
      control is obtained using the association with radiotherapy and chemotherapy.
      Intraoperative Radiation Therapy (IORT) represents an innovative therapeutic
      modality. PATIENTS AND METHODS: 141 patients, 97 with "high risk" cancer (T2N1-2
      or T3N0-2) and 44 with "locally advanced" tumor (T3N3, T4N0-3 or local
      recurrence). 64 patients with extraperitoneal "high risk" rectal cancer have been
      treated with preoperative radiotherapy (38 Gy), surgical excision and IORT (10
      Gy). In other 33 "high risk" cases, preoperative radio- (50.4 Gy) chemotherapy
      (Tomudex 2-3 mg), surgery and IORT (10 Gy) have been given. Fourty four patients
      with "locally advanced" rectal tumor have had external radiotherapy (48 Gy) +
      chemotherapy (5FU + Mitomicin C) preoperatively, surgery, IORT (10-15 Gy) and
      chemotherapy (5FU + Levamisolo) postoperatively. RESULTS: Among "high risk"
      patients, 52-83% of cases have had a sphincter-saving surgical procedure, 5-year
      local control is 93%, 5-year overall survival 80%, and 5-year disease free
      survival 77%. In 50-60% of "high risk" tumors treated with preoperative chemo
      radiotherapy the pathologic staging have found a T0-1 tumor. Among "locally
      advanced" primary tumors, 5-year local control is 90.9%, 5-year disease free
      survival 47.1%, 5-year overall survival 60.7%. Among patients treated for local
      recurrence, in 60% a complete tumor resection has been performed; 5-year local
      control is 79.5%, 5-year disease free survival 19.4%, 5-year overall survival
      41.4%. CONCLUSIONS: Integrated treatment with radiotherapy, chemotherapy, surgery
      and IORT has allowed a good local control and seems prolong survival also.

PMID- 11975412
TI  - [Postoperative radiotherapy of rectal carcinoma].
AB  - In the last 40 years, radiotherapy as gained a major role in the curative
      treatment of rectal carcinoma. Based on a reported incidence of local failure
      after surgery between 15% and 50%, in patients with T3-4 rectal cancer,
      postoperative radiation has been proposed in this group of patients. However,
      postoperative radiotherapy results associated with a relatively high incidence of
      acute and late toxicity and the reported improvement in local control attained
      statistical significance only in the MRC randomized trial. A recent publication
      suggests that postoperative radiation should probably be reserved to the subgroup
      of pT3 patients with unfavourable features. Postoperative radiation therapy is
      considered also for patients with G1-2 carcinoma treated with local excision, who
      do not show lymphatic or venous invasion, and for those with pT2 stage or pT1
      carcinoma with involved resection margins.

PMID- 11975413
TI  - [Postoperative chemotherapy in rectal carcinoma].
AB  - The natural history of rectal carcinoma requires to achieve strategies addressed
      both local control and the prevention of distant metastases. Based on the NCI
      Consensus Conference of 1990, the recommended adjuvant treatment for rectal
      carcinomas staged pT3, or with pathologically involved lymph nodes, is
      represented by concurrent chemoradiation. The role of chemotherapy in the
      adjuvant treatment of patients operated on for rectal tumor remains unclear also
      in patients treated with preoperative chemoradiation. The chemotherapeutic drugs
      to be used, and the potential role of chemotherapy alone for patients at low risk
      of local recurrence, should also be considered. In this analysis literature data
      regarding these issues are presented. Despite the absence of clear indications
      from published data, in patients with pathological B2 or C stage after
      preoperative chemoradiation it seems that adjuvant chemotherapy should be used.

PMID- 11975414
TI  - [Radiotherapy in pelvic recurrences of rectal cancer].
AB  - Patients with locally recurrent rectal carcinoma have an unfavourable prognosis
      for the high incidence of distant metastases, the infrequent feasibility of
      radical surgical resection, and, in these last cases, the high incidence of re
      recurrences. Based on the low resectability rate of pelvic recurrences, the clear
      impact of tumor diameter on resectability and outcome, and the documented
      possibility to achieve a significant tumor downstaging and downsizing with the
      use of concurrent chemoradiation, it is evident that the most promising treatment
      several authors have considered concurrent chemoradiation followed, if feasible,
      by radical resection. Furthermore, based on the high local and distant failure
      rate after surgery, the utilization of intraoperative radiation therapy (IORT)
      and adjuvant chemotherapy seems justified. Some published comparisons between
      patients treated with and without IORT seems to suggest the possible improvement
      in both local control and survival in these patients. Particularly interesting
      issues in this field are: 1) the definition of the most effective treatment
      modality (both in terms of radiation dose, fractionation and techniques, and
      drugs to be used concurrently to radiotherapy); 2) the analysis of the prognostic
      impact of several factors, with the aim of designing and validating staging
      systems of local rectal recurrences; 3) the possibility to treat with relatively
      high doses also patients previously irradiated on the pelvis.

PMID- 11975415
TI  - [Quality radiotherapy in rectal cancer].
AB  - The quality of radiotherapy significantly impacts on the results of treatment, in
      patients with rectal carcinoma, especially in terms of acute and late toxicity.
      Based on this assumption, the Italian Association of Radiation Oncology (AIRO)
      formulated a document aimed to define the standards of radiation treatment for
      rectal carcinomas. Two different levels of standard were described: a first
      level, considered as "minimal requirement", and a second level, considered as
      "optimal treatment". A retrospective evaluation, based on a questionnaire,
      revealed that in 1996, in most Italian Centers, patients affected by rectal
      carcinoma received radiation treatment within the first level of proposed
      standards. A subsequent analysis concerned the evaluation of the level of
      treatments applied in 2000. In this paper the radiotherapy standards proposed by
      the AIRO are described in the different phases of the radiation treatment.

PMID- 11975416
TI  - Conservative alternatives to radical surgery for favorable rectal cancers.
AB  - Selected cases of favorable rectal cancer can be treated with less than radical
      surgery. The literature demonstrates that excellent local control can be achieved
      using either local excision or carefully confined high dose radiation to treat
      the primary tumor site. Two treatments to the tumor site appear equally
      effective: local excision (usually a full thickness en bloc procedure) or low
      energy (50 kVp) endocavitary radiation. For many patients treated conservatively
      there is also a role for external beam radiation to the pelvis-this treats
      subclinical disease in regional nodes and around the tumor bed. The locoregional
      control for T1 lesions is excellent. For T2 lesions about 15% of patients can
      experience recurrence after conservative treatment. Close follow up of these
      patients is important, since local failures after conservative treatment are more
      amenable to salvage surgery than failures after standard radical surgery. Careful
      selection of cases, using endorectal ultrasound or MRI whenever possible, is
      important. The incidence of unexpected T3 disease or tumor at the margin of
      resection has been reported as high as 40% in series that do not utilize
      endorectal T staging.

PMID- 11975417
TI  - [Surgery and radiotherapy in rectal cancer: indications for anal sphincter
      conservation].
AB  - PURPOSE: Aim of this study is to evaluate the possible increase of sphincter
      preservation rate in locally advanced extraperitoneal rectal cancer after
      neoadjuvant treatment. METHODS: 123 patients with a T3 or N+ cancer of middle or
      lower rectum have been included in this study. Accurate measurement of pre
      treatment tumor distance from the anal canal and an individual judgment of the
      surgeon about the technical feasibility of a sphincter saving resection have been
      recorded. Two different protocols of concomitant preoperative chemoradiation have
      been adopted. Radiotherapy ranged from 37.8 to 50.4 Gy. Chemotherapy regimens
      included mitomycin-C 10 mg/m2; 5FU 1000 mg/m2 and c-DDP 60 mg/m2. All patients
      underwent surgery 4-8 weeks after the end of chemoradiation. RESULTS: 16 out of a
      total 121 resected patients (13%) had a complete histologically response at
      surgical specimen examination (pT0). The post-treatment variation of tumor
      distance from the anal canal was 1 cm. in 50% of cases, 2 cm. in 20% of cases and
      > 3 cm. in 10% of cases. 80% of patients (97/121) could benefit of a sphincter
      saving procedure compared to a pre-treatment expected rate of 55%. 69% of 70
      patients with a tumor of the distal rectum maintained their sphincter function;
      in particular, a sphincter saving procedure was made possible in 16 of 37
      patients (43%) with a tumor located in the distal 3 cm. of the rectum. No
      significant difference in sphincter saving rate was observed between the two
      different protocols of neoadjuvant treatment. DISCUSSION: Decrease of tumor size,
      post-treatment variation of tumor distance from the anal canal, histological
      downstaging and decrease of tumor fixity to adjacent structures are the main
      effects of neoadjuvant treatment which are responsible for an increase of
      sphincter saving rate. CONCLUSION: According to the presented data, neoadjuvant
      protocols of concomitant chemoradiation therapy are effective in increasing the
      rate of sphincter saving procedures in locally advanced cancer of distal rectum.

PMID- 11975418
TI  - Mast cell growth, differentiation, and death.
AB  - Mast cells (MC) begin development in the bone marrow. Following initial lineage
      commitment, the cells move into the vasculature as a committed progenitor (MCp)
      that is poorly phenotypically defined, but appears to be an agranular cell
      lacking the high-affinity IgE receptor characteristic of the mature tissue
      localized MC. Full maturation occurs after the cells move into the various
      tissues. In the mouse, MCp localizing in the connective tissues appear to
      differentiate into mature MC, whereas those localizing in the lung and mucosal
      compartment of the small intestine remain largely as committed MCp. Movement of
      the MCp into the small intestine is controlled by the alpha 4 beta 7 integrin,
      whereas the factors controlling movement into other tissues remain to be defined.
      Following an inflammatory stimulus, Th2-derived cytokines drive the maturation
      process of these MCps, leading to the mature mucosal MC hyperplasia associated
      with events such as an intestinal helminth infection and possibly human allergy
      such as asthma and rhinitis. The expanded MC number disappears as the stimulus
      resolves. Various routes are used in the resolution of the MC hyperplasia
      including apoptosis, shedding along with the villous epithelium, and
      recirculation back to the spleen for elimination. Unlike the reactive MC that
      appears in association with inflammation, the connective tissue-localized MC is a
      long-lived radiation-resistant cell, which appears to depend principally on the
      presence of stem cell factor (SCF) for its persistence.

PMID- 11975420
TI  - The diverse effects of mast cell mediators.

PMID- 11975422
TI  - Mastocytosis and disorders of mast cell proliferation.

PMID- 11975419
TI  - Mast cells. Receptors, secretagogues, and signaling.

PMID- 11975424
TI  - Target controlled infusion of rocuronium: selection of a pharmacokinetic model.

PMID- 11975421
TI  - Importance of mast cells in the pathophysiology of asthma.

PMID- 11975423
TI  - Regulation of mast cell-mediated innate immunity during early response to
      bacterial infection.
AB  - Although the area of research on the role of MCs in innate immunity is relatively
      new, a number of studies that are reviewed here provide substantial evidence that
      MCs play a critical role in host immune defense against gram-negative bacteria.
      The studies show that mast cells have the ability to recognize and engulf
      bacteria and they release a number of inflammatory mediators including
      interleukin (IL)-4, IL-6, IL-10, TNF alpha, and leukotrienes in response to
      bacterial challenge. MC-derived TNF alpha and leukotrienes are shown to be
      important for bacterial clearance and early recruitment of phagocytic help at the
      site of infection. Studies directed at elucidating the molecular mechanisms
      associated with mast cell recognition of bacteria and subsequent events leading
      to mast cell mediator release revealed that GPI anchored CD48 molecule present on
      the cell surface of mast cells serves as a receptor for the bacterial adhesion
      molecule, FimH. The ligation of CD48 receptor by FimH-expressing bacteria results
      in bacterial uptake into caveolar chambers. This distinct mechanism of bacterial
      uptake promotes bacterial survival inside the cytosol of the mast cells. Although
      the exact mechanism(s) of how MC-dependent inflammatory responses are regulated
      is currently not known, recent studies have shown that complement, CD11 beta/CD18
      (Mac-1) and protein tyrosine kinase JAK3, and TLR4 are important for the full
      expression of MC-dependent innate immunity in mice.

PMID- 11975425
TI  - A randomized study of the efficacy and recovery of remifentanil-based and
      alfentanil anaesthesia with desflurane or sevoflurane for gynecological surgery.
AB  - We performed a prospective, randomized study comparing the efficacy and safety of
      the combination of remifentanil and the newer volatile anaesthetics desflurane
      and sevoflurane with a conventional anaesthetic technique using alfentanil and
      desflurane. Forty five ASA class I or II female patients were randomly assigned
      to one of three groups. Following induction with propofol patients received a
      continuous infusion of remifentanil in combination with either 0.5 MAC desflurane
      (n = 15) or sevoflurane (n = 15), a third group (n = 15) received 1 MAC of
      desflurane with bolus doses of alfentanil for maintenance of anaesthesia.
      Remifentanil infusion and alfentanil (bolus) were titrated to responses to
      surgical stimuli while the concentration of volatile agents was kept unchanged.
      The number of responses to surgical stimuli was similar in the two remifentanil
      groups and higher in the alfentanil-desflurane group. Recovery times were similar
      in all groups. The incidence of postoperative side effects was high in the three
      groups. No awareness occurred and patient satisfaction in the two remifentanil
      groups was comparable to the conventional anaesthetic technique.

PMID- 11975426
TI  - Actigraphic assessment of the preoperative hypnotic effects of brotizolam and
      zopiclone.
AB  - Brotizolam and zopiclone have a common ability to bind to the benzodiazepine
      recognition site and have been used as useful preoperative hypnotics. The aim of
      the present study was the quantitative evaluation of the preoperative hypnotic
      effects of brotizolam and zopiclone by actigraphy. Forty patients received
      brotizolam 0.25 mg (group B) or zopiclone 7.5 mg (group Z) in randomized manner
      at 21:30 on the night before surgery. Sleep and awake was identified by wrist
      activity measured with a motion-logger actigraph. Sleep time was assessed in
      total period from 22:00 to 6:00 and its 4 subdivided 2-hour periods (22:00-24:00,
      24:00-2:00, 2:00-4:00, 4:00-6:00). The total sleep time in group B (448 +/- 23
      min) was significantly longer than that in group Z (416 +/- 43 min). Group Z
      showed a significant reduction in sleep time in period 4 (4:00-6:00), compared
      with other periods, whereas group B did not show any difference among 4 periods.
      In comparison of each period between 2 groups, group B showed significant longer
      sleep time in period 4. An actigraphic assessment of sleep time has demonstrated
      the quantitative difference of the effects of brotizolam and zopiclone as
      preoperative hypnotics.

PMID- 11975427
TI  - TOF-tube, a new protection for acceleromyography, compared with the TOF-Guard/TOF
      Watch arm board.
AB  - Neuromuscular blockade monitoring at the adductor pollicis has become easier
      using acceleromyography. In order to guarantee a reliable analysis of its
      acceleration, the thumb movement has to be free and protected from external
      influences. To this end, we describe here-in two hand fixation- and protection
      devices for use with acceleromyography. After a bolus of 0.3 mg/kg rocuronium, we
      compared acceleromyography data obtained simultaneously on both hands with, on
      one side, the cumbersome TOF-Guard/TOF-Watch arm board, and the smaller and
      handier TOF-tube on the other. Results showed little differences between the two
      devices. Yet, a short and clinically irrelevant delay was observed for TOF-tube
      data during recovery. This was probably caused by a difference in thumb position
      and repositioning technique. In conclusion, the more convenient TOF-tube can be
      used as well as the TOF-Guard/TOF-Watch arm board in daily clinical practice.

PMID- 11975428
TI  - Miss'n-Mix and Mimics.

PMID- 11975430
TI  - Belgian standards for patient safety in anesthesia. An update.

PMID- 11975429
TI  - Large subcutaneous hematoma complicating epidural block.
AB  - We present a case of a large subcutaneous hematoma in the lumbar region that
      occurred after epidural block was performed for the relief of labor pain.
      Epidural analgesia was begun in a young and healthy primigravida. Eight hours
      later, she needed an emergency cesarean section. Before anesthesia, blood was
      observed flowing freely around the site of the catheter insertion. General
      anesthesia was administered. Postoperative computed tomography showed a large
      subcutaneous hematoma in the lumbar region. Her postpartum course was complicated
      by an unexplained fever, which responded to antibiotic therapy and warranted
      prolonged hospitalization. Coagulation and bleeding studies were normal. We
      conclude subcutaneous hematoma after epidural block can cause significant
      morbidity and should be added to the list of neuroaxial block complications.

PMID- 11975431
TI  - Pop drinking, poor diet lead to dental troubles.

PMID- 11975432
TI  - When employees walk out on you.

PMID- 11975433
TI  - The sweet and sour of pediatric caries.

PMID- 11975434
TI  - Coding for routine periodontal treatment: Part 4.

PMID- 11975435
TI  - Reimbursement problems!

PMID- 11975436
TI  - Debt reduction basics for new dentists.

PMID- 11975437
TI  - Take another look at the professional protector plan.

PMID- 11975438
TI  - Oral pathology quiz #5.

PMID- 11975439
TI  - They never saw it coming. Four dentists, four true malpractice cases.

PMID- 11975441
TI  - Case study: a tragically botched emergency.

PMID- 11975440
TI  - Delegation of duties: are you breaking the law?

PMID- 11975442
TI  - HIV: the road ahead.

PMID- 11975443
TI  - Quality management of sequence-based methods for measuring HIV-1 drug resistance.

PMID- 11975445
TI  - A sensitive replicative system to assess HIV-1 drug resistance.

PMID- 11975444
TI  - Reducing high-risk drinking by using personalized blood alcohol cards.

PMID- 11975446
TI  - Use of artificial intelligence in monitoring HIV disease.

PMID- 11975447
TI  - Real-time point-of-care molecular detection of infectious disease agents.

PMID- 11975448
TI  - Cardiac troponin: redefining the detection of myocardial infarction.

PMID- 11975449
TI  - The HIPAA privacy rule: clinical laboratories must comply.

PMID- 11975450
TI  - The effect of adulterants on urine screen for drugs of abuse: detection by an on
      site dipstick device.

PMID- 11975451
TI  - Role of HIV phenotypic assays in the management of HIV infection.
AB  - Contemporary phenotypic assays such as the PhenoSense HIV assay are more
      straightforward to interpret than genotyping results because they do not require
      the expert interpretation of complex mutation patterns. The drug susceptibility
      data provides information for the clinician to select a treatment regimen
      effective against the predominant viral population circulating in the patient's
      blood. Compared to traditional phenotypic assays, the PhenoSense HIV assay uses a
      virus vector and a luciferase reporter gene to provide a quick and sensitive
      measure of viral replication. The main use of phenotypic assays at present is to
      identify those antiretroviral drugs that still retain activity against the
      patient's virus. Phenotypic assays are useful to provide guidance after treatment
      failure and to select a proper combination of drugs prior to initiation of
      therapy. They are also useful to detect transmission of resistance virus and to
      monitor HIV patients during early viral rebound. In essence, phenotypic testing
      provides information to target antiretroviral therapy against the predominant HIV
      variant in the patient for a prolonged suppression of viral replication,
      decreased mortality, and lower health-care costs.

PMID- 11975452
TI  - Losing their voice?

PMID- 11975453
TI  - When the bombing stops.

PMID- 11975454
TI  - Not for love nor money.

PMID- 11975455
TI  - Defining moment. Interview by Colin Parish.

PMID- 11975456
TI  - Need to know.

PMID- 11975457
TI  - Breast care: the shape of things to come.

PMID- 11975458
TI  - Free falling.

PMID- 11975459
TI  - Skin deep.

PMID- 11975467
TI  - Therapeutic directions in acute inpatient psychiatric nursing.
AB  - BACKGROUND: The role of nurses in caring for acute psychiatric inpatients has
      traditionally been a holistic one, involving one-to-one nurse-patient
      relationships and the therapeutic use of self. Over the years, a more medical
      model has emerged, including cognitive-behavioural therapy and monitoring of
      medication. At the same time, there has been a reaction against the 'observation
      culture' that has existed in many hospitals. This article considers the best way
      forward for psychiatric nursing. CONCLUSION: A psychosocial model seems to
      provide the most promising framework for the development of psychiatric inpatient
      nursing. However, this must not be at the expense of the traditional holistic,
      humanistic approach that is valued by patients, carers and nurses.

PMID- 11975468
TI  - Gerontological nurse specialists.
AB  - This article focuses on the development of a new role highlighted in The NHS Plan
      (DoH 2000a), nurse specialist for older people or gerontological nurse
      specialist.

PMID- 11975470
TI  - An overview of foot disease in patients with diabetes.
AB  - Effective management of diabetic foot disease requires a multidisciplinary
      approach and good communication between all healthcare professionals involved.
      This article provides an overview of the main factors that need to be considered
      when assessing patients with diabetic foot disease.

PMID- 11975472
TI  - A risk worth taking.

PMID- 11975475
TI  - Synthesis and biological evaluation of hyperforin analogues. Part I. Modification
      of the enolized cyclohexanedione moiety.
AB  - Modification of the St. John's wort acylphloroglucinol constituent, hyperforin
      (1), by acylation, alkylation, and oxidation resulted in detrimental effects on
      the inhibition of the synaptosomal accumulation of serotonin, showing the
      existence of definite structure-activity relationships in this in vitro test
      system and highlighting the role of the enolized cyclohexanedione moiety for
      activity on neurotransmitter reuptake.

PMID- 11975476
TI  - Evidence for biosynthesis of pseudophrynamine alkaloids by an Australian
      myobatrachid frog (pseudophryne) and for sequestration of dietary pumiliotoxins.
AB  - Australian myobatrachid frogs of the genus Pseudophryne have only two classes of
      alkaloids in skin extracts, pseudophrynamines (PSs) and pumiliotoxins (PTXs). The
      former are unique to such Australian frogs, while the PTXs occur worldwide in all
      other genera of frogs/toads that contain lipophilic alkaloids. The major alkaloid
      of wild-caught frogs from one population of Pseudophryne semimarmorata was PTX
      267C, while PSs were only minor or trace alkaloids. Captive-raised frogs from the
      same parental stock had no PTXs, but had larger amounts of PSs. A PTX fed to
      captive-raised frogs accumulated into skin along with dihydro and hydroxy
      metabolites. Thus, Pseudophryne frogs appear to biosynthesize PSs, but to
      sequester into skin dietary PTXs. In addition, biosynthesis of PSs appears
      reduced when high levels of dietary PTXs have accumulated into skin. This is the
      first evidence indicating that certain frogs are capable of synthesizing rather
      than merely sequestering alkaloids. A wide range of PSs, including many with
      molecular weights >500, were detected using both GC-mass spectral and LC-mass
      spectral analysis.

PMID- 11975477
TI  - C-5-substituted antifeedant silphinene sesquiterpenes from Senecio palmensis.
AB  - The new sesquiterpenes, 5alpha-senecioyloxysilphinen-3-one (5), 5alpha
      tigloyloxysilphinen-3-one (7), and 3beta-hydroxy-5alpha-angeloyloxysilphinene
      (8), and the known compounds (6S)-2,10-bisaboladien-1-one (1), 6,7-epoxy-3(15)
      caryophyllene (2), 6,7-epoxy-2,9-humuladiene (3), 5alpha-angeloyloxysilphinen-3
      one (4), and 5alpha-acetoxysilphinen-3-one (6) were isolated from bioactive
      fractions of Senecio palmensis. The structures of these compounds were
      established by spectroscopic analysis and chemical evidence. The semisynthetic
      analogues silphinen-3,5-dione (9), 5alpha-hydroxysilphinen-3-one (10), 5beta
      hydroxysilphinen-3-one (11), 5beta-acetoxysilphinen-3-one (12), and 5beta
      isobutyryloxysilphinen-3-one (13) were generated to carry out a structure
      activity study on the antifeedant action of these molecules against several
      divergent insect species.

PMID- 11975479
TI  - Eight new prenylcoumarins from Phebalium clavatum.
AB  - The aerial parts of Phebalium clavatum yielded eight new 3-prenylated coumarins,
      phebaclavin A-H (1-8). Their structures were established on the basis of their
      NMR and mass spectral data. In addition, seven known compounds were also
      isolated, including two 8-geranyloxy linear furocoumarins previously obtained
      from Phebalium tuberculosum ssp. megaphyllum, included in the same section of the
      genus.

PMID- 11975478
TI  - Lepadins F-H, new cis-decahydroquinoline alkaloids from the Australian ascidian
      Aplidium tabascum.
AB  - Chemical investigation of a Great Barrier Reef ascidian, Aplidium tabascum, has
      resulted in the isolation of three new cis-decahydroquinoline alkaloids, lepadins
      F-H (4-6). The three new compounds differ from the previously isolated lepadins A
      C (1-3) in that they contain a fully saturated 5-hydroxyoctyl side chain attached
      at C-5, an unsaturated eight-carbon ester moiety attached to C-3, and opposite
      stereochemistry at C-5 and C-3. Lepadins G (5) and H (6) are epimers at C-2. NMR
      and molecular modeling studies indicated that the three new compounds adopt a
      chair-chair conformation in which the nitrogen equatorially substitutes the
      cyclohexyl ring. This contrasts with lepadins A-C (1-3), which adopt a chair
      chair conformation in which the nitrogen axially substitutes the cyclohexyl ring.

PMID- 11975480
TI  - Inhibition of tumor-promoting effects by poricoic acids G and H and other
      lanostane-type triterpenes and cytotoxic activity of poricoic acids A and G from
      Poria cocos.
AB  - The structures of two novel 3,4-seco-lanostane-type triterpenes isolated from the
      sclerotium of Poria cocos were established to be 16alpha-hydroxy-3,4-seco-lanosta
      4(28),8,24-triene-3,21-dioic acid (1; poricoic acid G) and 16alpha-hydroxy-3,4
      seco-24-methyllanosta-4(28),8,24(24(1))-triene-3,21-dioic acid (2; poricoic acid
      H) on the basis of spectroscopic methods. These two, and eight other known
      compounds isolated from the sclerotium, poricoic acid B (3), poricoic acid A (4),
      tumulosic acid (5), dehydrotumulosic acid (6), 3-epidehydrotumulosic acid (7),
      polyporenic acid C (8), 25-hydroxy-3-epidehydrotumulosic acid (9), and
      dehydroabietic acid methyl ester (10), showed potent inhibitory effects on
      Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor
      promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Evaluation of the
      cytotoxicity of compounds 1 and 4 against human cancer cell lines revealed that 1
      was significantly cytotoxic to leukemia HL-60 cells [GI(50) (concentration that
      yields 50% growth) value 39.3 nM], although it showed only moderate cytotoxicity
      to the other cells. Compound 4 exhibited moderate cytotoxicity to all of the
      cancer cell lines tested.

PMID- 11975481
TI  - A mechanistic dehydration study with [2-(13)C]-DIMBOA.
AB  - Dehydration of a 2-(13)C-labeled synthetic sample of the natural aglucone 2,4
      dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one ([2-(13)C]-DIMBOA, 10) using N
      ethoxycarbonyltrichloroacetaldimine led to 3-formyl-6-methoxybenzoxazolin-2(3H)
      one ((13)C-labeled FMBOA, 11) with complete transfer of the (13)C label into the 
      CHO group. On the basis of this finding, a mechanism for the dehydration is
      proposed.

PMID- 11975482
TI  - New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata.
AB  - Three new monotetrahydrofuran annonaceous acetogenins, muricin H (1), muricin I
      (2), and cis-annomontacin (3), along with five known acetogenins, annonacin,
      annonacinone, annomontacin, murisolin, and xylomaticin, were isolated from the
      seeds of Annona muricata. Additionally, two new monotetrahydrofuran annonaceous
      acetogenins, cis-corossolone (4) and annocatalin (5), together with four known
      ones, annonacin, annonacinone, solamin, and corossolone, were isolated from the
      leaves of this species. The structures of all new isolates were elucidated and
      characterized by spectral and chemical methods. These new acetogenins exhibited
      significant activity in in vitro cytotoxic assays against two human hepatoma cell
      lines, Hep G(2) and 2,2,15. Compound 5 showed a high selectivity toward the Hep
      2,2,15 cell line.

PMID- 11975484
TI  - Dimeric guaianolides and a fulvenoguaianolide from Artemisia myriantha.
AB  - The aerial parts of Artemisia myriantha have afforded one new fulvenoguaianolide
      and four dimeric guaianolides in addition to seven known guaianolides. The
      structures of all the compounds were elucidated by 2D NMR. It is speculated that
      the dimeric guianolides are formed via Diels-Alder type reactions of
      fulvenoguaianolide derivatives.

PMID- 11975483
TI  - New antiinfective and human 5-HT2 receptor binding natural and semisynthetic
      compounds from the Jamaican sponge Smenospongia aurea.
AB  - In addition to the sesquiterpene-phenol aureols (1), 6'-chloroaureol (2), and
      aureol acetate (3), eight indole alkaloids including the new N-3'
      ethylaplysinopsin (9) have been isolated from the Jamaican sponge Smenospongia
      aurea. Makaluvamine O (10), a new member of the pyrroloiminoquinone class, was
      also isolated. The structures were characterized by spectroscopic methods, and
      two new derivatives of aureol were prepared to optimize the biological activity.
      Aureol N,N-dimethyl thiocarbamate (1a) and 6-bromoaplysinopsin (7) exhibit
      significant antimalarial and antimycobacterial activity in vitro. Compound 6
      showed activity against the Plasmodium enzyme plasmepsin II. The 6-bromo-2'-de-N
      methylaplysinopsin (6), 6-bromoaplysinopsin (7), and N-3'-ethylaplysinopsin (9)
      displaced high-affinity [(3)H]antagonist ligands from cloned human serotonin 5
      HT(2) receptor subtypes, whereas the other compounds tested did not. Remarkably,
      the 6-bromo-2'-de-N-methylaplysinopsin (6) showed a > 40-fold selectivity for the
      5-HT(2C) subtype over the 5-HT(2A) subtype.

PMID- 11975485
TI  - Malevamide D: isolation and structure determination of an isodolastatin H
      analogue from the marine cyanobacterium Symploca hydnoides.
AB  - Malevamide D (1), a highly cytotoxic peptide ester, and the known compound
      curacin D (5) were isolated from a Hawaiian sample of Symploca hydnoides. The
      structure of 1 was elucidated by spectroscopic analysis including NMR and high
      resolution MS/MS. Partial stereochemical assignments of 1 were made by chiral
      HPLC analysis of acid and base hydrolysates. Malevamide D (1) demonstrated
      toxicity against P-388, A-549, HT-29, and MEL-28 cell lines in the subnanomolar
      range, while curacin D (5) was weakly cytotoxic. Malevamide D (1) is closely
      related to isodolastatin H (2), which was previously isolated in low yield from
      the sea hare Dolabella auricularia. A second Hawaiian sample of S. hydnoides
      yielded curacin D (5) along with the known dolastatin-10 analogue symplostatin-1
      (3).

PMID- 11975486
TI  - Thorectandrols C, D, and E, new sesterterpenes from the marine sponge
      Thorectandra sp.
AB  - Extracts of the marine sponge Thorectandra sp. have been found to contain three
      new sesterterpenes, thorectandrols C (4), D (5), and E (6), together with the
      known compounds luffarin R (7), luffarin V (8), and palauolide (9). The
      structures were determined by extensive NMR spectral data analysis. Their
      relative stereochemistry was defined using NOE correlations and coupling
      constants, while CD data were used to suggest their absolute stereochemistry.
      Cytotoxicity data for compounds 4-9 as well as the previously reported compounds
      thorectandrols A and B and palauolol (1-3) against six or more human tumor cell
      lines are also reported.

PMID- 11975487
TI  - Four new alkaloids from Consolida glandulosa.
AB  - The structures of four new hetisine-type diterpenoids, 9-deoxyglanduline (1),
      glandulosine (2), 11,13-O-diacetylglanduline (3), and 9-O-acetylglanduline (4),
      isolated from Consolida glandulosa, were determined by two-dimensional NMR
      techniques. All the structures of these compounds were substantiated by a single
      crystal X-ray analysis performed on compound 3.

PMID- 11975488
TI  - Synthesis and structure-activity relationship study of lamellarin derivatives.
AB  - Ten derivatives (3-12) of marine alkaloid lamellarin D (1) were synthesized and
      evaluated for cytotoxicity against a HeLa cell line in an effort to examine their
      structure-activity relationships. It appeared that the hydroxyl groups at
      positions C-8 and C-20 of 1 were important structural requirements for cytotoxic
      activity, while the hydroxyl group at C-14 and the two methoxy groups at C-13 and
      C-21 were not necessary for the activity.

PMID- 11975489
TI  - Immunomodulatory proanthocyanidins from Ecdysanthera utilis.
AB  - Two new A-type proanthocyanidins have been isolated from Ecdysanthera utilis and
      identified as epicatechin-(4beta-->8,2beta-->O-->7)-epicatechin-(4beta-->8)
      epicatechin (5) and epicatechin-(4beta-->8)-epicatechin-(4beta-->8,2beta-->O-->7)
      epicatechin-(4beta-->8)-epicatechin (6), respectively. The structure-related
      components epicatechin (1), procyanidin B2 (2), proanthocyanidin A1 (3),
      proanthocyanidin A2 (4), and aesculitannin C (7) were also isolated. All of these
      compounds were identified and evaluated for immunopharmacological activity. Human
      peripheral blood mononuclear cells (PBMC) were used as target cells, and cell
      proliferation was determined by (3)H-thymidine uptake. The results indicated that
      compound 3 suppressed PBMC proliferation activated with phytohemagglutinin (PHA).
      The inhibitory mechanisms may involve the blocking of interleukin-2 (IL-2) and
      interferon-gamma (IFN-gamma) production, since compound 3 attenuated IL-2 and IFN
      gamma production of PBMC in a dose-dependent manner. Therefore, it is suggested
      that immunomodulatory agents are present in E. utilis.

PMID- 11975490
TI  - Monoterpene hydroperoxides with trypanocidal activity from Chenopodium
      ambrosioides.
AB  - Four monoterpene hydroperoxides were isolated from aerial parts of Chenopodium
      ambrosioides along with ascaridole (1), the anthelmintic principle of this plant,
      as anti-trypanosomal compounds. The structures of these monoterpenes were
      determined to be (-)-(2S,4S)- and (-)-(2R,4S)-p-mentha-1(7),8-dien-2
      hydroperoxide (2a and 3a) and (-)-(1R,4S)- and (-)-(1S,4S)-p-mentha-2,8-dien-1
      hydroperoxide (4a and 5a) on the basis of spectroscopic methods and chemical
      correlations. In vitro trypanocidal activities of ascaridole (1) and these
      hydroperoxides (2a-5a) against epimastigotes of Trypanosoma cruzi were 23, 1.2,
      1.6, 3.1, and 0.8 microM, respectively. Fresh leaves of C. ambrosioides also
      contained isomeric hydroperoxides 6a and 7a, and the content ratio of 2a-7a
      suggested that these hydroperoxides were formed through the singlet-oxygen
      oxidation of limonene.

PMID- 11975491
TI  - Alkaloids from Consolida oliveriana.
AB  - Four new diterpenoid alkaloids, olivimine (1), olividine (2), 8-O
      methylcolumbianine (3), and 7alpha-hydroxycossonidine (4), were isolated from the
      aerial parts of Consolida oliveriana. Compounds 1 and 2, 3, and 4 belong to the
      lycoctonine-azomethine, aconitine, and hetisine types, respectively, and their
      structures were elucidated by spectral data interpretation.

PMID- 11975492
TI  - Evaluation of glucoiberin reference material from Iberis amara by spectroscopic
      fingerprinting.
AB  - Increasing worldwide regulations require increased efforts toward validation of
      analytical and pharmacological reference materials. A detailed survey of
      glucoiberin, a prototype lead constituent of therapeutic value, using 1D/2D NMR,
      MS, and X-ray spectroscopy provided precise phytochemical data for structure
      assignment. Quantitative reference validation was achieved by the recently
      proposed qNMR method.

PMID- 11975493
TI  - New cytotoxic 6,7-cis and 6,7-trans configured guaianolides from Warionia
      saharae.
AB  - Using cytotoxicity against the KB cancer cell line (ATCC CCL17) as a lead,
      bioactivity-guided fractionation of the MeOH-soluble part of the DCM extract of
      Warionia saharae leaves led to the isolation of six new cytotoxic guaianolide
      type sesquiterpene lactones (1-6). Besides two guaianolides showing the common
      6,7-trans fused lactone ring (3 and 4), four compounds exhibiting the more rare
      6,7-cis configuration (1,2 and 5,6) were also isolated. Compounds 1, 2, 5, and 6
      showed an unprecedented ether bridge between C-2 and C-4. The structures were
      deduced from extensive 1D and 2D NMR spectroscopy ((1)H, (13)C, DQF-COSY, HSQC,
      HMBC, ROESY), as well as mass spectrometry (EI and HR-MALDI). Cytotoxicity
      testing against the KB cancer cell line revealed IC(50) values of 1.0 (1), 4.5
      (2), 1.7 (3), 2.0 (4), 3.3 (5), and 5.5 (6) microg/mL.

PMID- 11975494
TI  - New seco-prezizaane-type sesquiterpenes, jiadifenin with neurotrophic activity
      and 1,2-dehydroneomajucin from Illicium jiadifengpi.
AB  - Two new seco-prezizaane-type sesquiterpenes, 1,2-dehydroneomajucin (1) and
      jiadifenin (2), were isolated from the methanol extract of the pericarps of
      Illicium jiadifengpi, indigenous to the southern part of China. Their structures
      were elucidated on the basis of NMR data. Compound 2, which is an equilibrated
      mixture of the epimers 2a and 2b on the C-10 acetal carbon, is the first example
      of a majucin-type seco-prezizaane with an oxo-function at the C-10 position. The
      proposed structure for 2 was unambiguously confirmed by chemical conversion of
      the known sesquiterpene (2S)-hydroxy-3,4-dehydroneomajucin (5) to 2. Compounds 2
      and 5 were found to significantly promote neurite outgrowth in primary cultures
      of fetal rat cortical neurons at concentrations from 0.1 to 10 microM.

PMID- 11975495
TI  - Sesquiterpenoids from Tithonia diversifolia with potential cancer chemopreventive
      activity.
AB  - Activity-guided fractionation of an ethyl acetate extract of the aerial parts of
      Tithonia diversifolia, using an antiproliferation bioassay performed with human
      colon cancer (Col2) cells, led to the isolation of three new sesquiterpenoids,
      2alpha-hydroxytirotundin (1), tithofolinolide (2), and 3alpha-acetoxydiversifolol
      (3), along with eight known sesquiterpene lactones, 3beta-acetoxy-8beta
      isobutyryloxyreynosin (4), tagitinin C (5), 1beta,2alpha-epoxytagitinin C (6),
      4alpha,10alpha-dihydroxy-3-oxo-8beta-isobutyryloxyguaia-11(13)-en-12,6alpha-olide
      (7), 3alpha-acetoxy-4alpha-hydroxy-11(13)-eudesmen-12-oic acid methyl ester,
      17,20-dihydroxygeranylnerol, tagitinin A, and tirotundin. These isolates were
      evaluated for their potential as cancer chemopreventive agents, by measuring
      antiproliferative activity in Col2 cells and induction of cellular
      differentiation in human promyelocytic leukemia (HL-60) cells. Selected compounds
      were then investigated for their ability to inhibit 7,12
      dimethylbenz[a]anthracene-induced preneoplastic lesions in a mouse mammary organ
      culture assay. Among these isolates, 5 and 6 showed significant antiproliferative
      activity, 2, 4, and 7 induced HL-60 cellular differentiation, and 4 significantly
      inhibited (63.0% at 10 microg/mL) lesion formation in the mouse mammary organ
      culture assay. The chemical structures of 1-3 were elucidated by spectroscopic
      analysis. The absolute configurations of 1 and 2 were determined by Mosher ester
      methodology.

PMID- 11975497
TI  - Plant analysis by butterflies: occurrence of cyclopentenylglycines in
      Passifloraceae, Flacourtiaceae, and Turneraceae and discovery of the novel
      nonproteinogenic amino acid 2-(3'-cyclopentenyl)glycine in Rinorea.
AB  - Following records about feeding habits of nymphalid butterflies, a novel
      nonproteinogenic L-amino acid, (S)-2-(3'-cyclopentenyl)glycine (11), was
      discovered in Rinorea ilicifolia, a species where the presence of a
      cyclopentanoid natural product of this kind was neither known nor anticipated
      from the taxonomic point of view. Another novel amino acid, (2S,1'S,2'S)-2-(2'
      hydroxy-3'-cyclopentenyl)glycine (12), the stereochemistry of which was
      determined by single-crystal X-ray diffraction, was shown to occur in species
      belonging to Flacourtiaceae, Passifloraceae, and Turneraceae. These species, many
      of which serve as hosts for nymphalid butterflies (Acraeinae, Heliconiinae,
      Argynninae), also produce 2-(2'-cyclopentenyl)glycine. Cyclopentenylglycines are
      proposed to be novel chemical recognition templates for plant-insect
      interactions. Ratios between the epimers of (2S)-2-(2'-cyclopentenyl)glycine,
      which co-occur in plants, were determined by (1)H NMR spectroscopy. Contrary to a
      previous report, the (2S,1'R) epimer always appears to predominate over the
      (2S,1'S) epimer. Stereochemical aspects of biosynthesis of natural cyclopentanoid
      cyanogenic glycosides are discussed in relation to these findings.

PMID- 11975496
TI  - New diterpenes and norditerpenes from the fruits of Vitex rotundifolia.
AB  - A new labdane-type diterpene, vitexifolin A (1), a new clerodane-type diterpene,
      vitexifolin B (2), a new abeoabietane-type diterpene, vitexifolin C (3), and two
      new norlabdane-type diterpenes, vitexifolin D (4) and vitexifolin E (5), were
      isolated from the fruits of Vitex rotundifolia, along with a known halimane-type
      diterpene, vitetrifolin D (6), two known norlabdane-type diterpenes, trisnor
      gamma-lactone (7) and iso-ambreinolide (8), and three known flavonoids, casticin
      (9), artemetin (10), and 5,3'-dihydroxy-6,7,4'-trimethoxyflavanone (11). Their
      chemical structures were determined on the basis of spectroscopic data. Casticin
      (9) exhibited considerable growth inhibitory activity against human lung cancer
      cells (PC-12) and human colon cancer cells (HCT116) using the MTT assay.

PMID- 11975498
TI  - New lanostanoids, elfvingic acids A-H, from the fruit body of Elfvingia
      applanata.
AB  - Eight new lanostanoids, 12alpha,15beta-dihydroxy-3,7,11,23-tetraoxolanost
      8,(20Z)(22)-dien-26-oic acid (1), 7beta,8beta-epoxy-15beta,20S-dihydroxy-3,12,23
      trioxolanost-9(11),16-dien-26-oic acid (2), 7beta,8beta-epoxy-3beta,15beta,20S
      trihydroxy-12,23-dioxolanost-9(11),16-dien-26-oic acid (3), 7beta,8beta-epoxy
      2alpha,3beta,15beta,20S-tetrahydroxy-12,23-dioxolanost-9(11),16-dien-26-oic acid
      (4), 7beta,8beta-epoxy-3beta,15beta,20S,28-tetrahydroxy-12,23-dioxolanost
      9(11),16-dien-26-oic acid (5), 7beta,8beta-epoxy-3beta,15beta,19,20S-tetrahydroxy
      12,23-dioxolanost-9(11),16-dien-26-oic acid (6), 8beta,15beta,20S-trihydroxy
      3,7,12,23-tetraoxolanost-9(11),16-dien-26-oic acid (7), 7alpha,8alpha-epoxy
      15beta,23xi-dihydroxy-12-oxo-3,4-secolanost-4(28),9(11),(20Z)(22)-trien-3,26
      dioic acid (8), and the methyl ester of 8 (8a) were isolated from the fruit
      bodies of Elfvingia applanata. Their structures were established primarily by NMR
      experiments, and their biological activity against Kato III and Ehlrich cells was
      investigated.

PMID- 11975500
TI  - Total synthesis and bioactivity of some naturally occurring pterulones.
AB  - The naturally occurring pterulones 1, 3, and 13 were synthesized in high overall
      yield from readily available methyl 3-(2-propenyl)-4-(2-propenyloxy)benzoate (6)
      by employing ring-closing metathesis (RCM) as a key step. The biological
      activities of the synthesized pterulones were tested using cells of
      Rhodotorulaglutinis and Saccharomyces cerevisiae.

PMID- 11975499
TI  - Three new triterpene saponins from two species of Carpolobia.
AB  - Three new acetylated triterpene saponins 1-3 were isolated from the roots of
      Carpolobia alba and C. lutea. Their structures were established mainly by 2D NMR
      techniques as 3-O-beta-D-glucopyranosylpresenegenin-28-O-beta-D-galactopyranosyl
      (1-->4)-[beta-D-xylopyranosyl-(1-->3)]-beta-D-xylopyranosyl-(1-->4)-alpha-L
      rhamnopyranosyl-(1-->2)-(3,4-di-O-acetyl)-beta-D-fucopyranosyl ester, 3-O-beta-D
      glucopyranosylpresenegenin-28-O-beta-D-galactopyranosyl-(1-->4)-[alpha-L
      arabinopyranosyl-(1-->3)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1
      ->2)-(3,4-di-O-acetyl)-beta-D-fucopyranosyl ester, and 3-O-beta-D
      glucopyranosylpresenegenin-28-O-beta-D-xylopyranosyl-(1-->4)-[beta-D
      apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-(3,4-di-O-acetyl)-beta-D
      fucopyranosyl ester, respectively.

PMID- 11975501
TI  - Triterpenoid constituents of Raulinoa echinata.
AB  - A phytochemical investigation of the stems of the South Brazilian endemic species
      Raulinoa echinata has led to the isolation of two new methoxylated protolimonoid
      epimers (1 and 2) together with the known melianone and melianodiol. The leaves
      afforded three glabretal-type triterpene derivatives esterified by N
      methylanthranilic acid (3-5). Compounds 1 and 2 displayed weak inhibitory
      activity when assayed in vitro against trypomastigote forms of Trypanosoma cruzi.
      Compounds 1-5 were inactive in a brine shrimp (Artemia salina) lethality test.

PMID- 11975502
TI  - Antimicrobial activities of a new schizozygane indoline alkaloid from Schizozygia
      coffaeoides and the revised structure of isoschizogaline.
AB  - Extracts from Schizozygia coffaeoides showed antimicrobial activity against
      fungal and bacterial species. Alkaloids isolated using bioassay-guided
      fractionation were isoschizogaline, schizogynine, and a new indoline alkaloid,
      7,8-dehydro-19beta-hydroxyschizozygine, shown to be the most active antifungal
      compound. The structure of isoschizagaline, the only active antibacterial, is
      revised on the basis of NMR analysis.

PMID- 11975503
TI  - Large-scale isolation and crystallization of epothilone D from Myxococcus xanthus
      cultures.
AB  - The introduction of the epothilone polyketide synthase (PKS) into Myxococcus
      xanthus has enabled the heterologous production of epothilone D (1) on a large
      scale. To isolate this valuable product from the fermentation medium, an
      economical, scalable, and high-yielding purification process was developed. With
      the crystallization of 1 from a binary solvent system that consisted of ethanol
      and water, the product was recovered as white crystals with a final purity of >
      or =97% (w/w). This is the first reported crystallization of 1.

PMID- 11975504
TI  - Comparative study of differentiation levels and valepotriate content of in vitro
      cultures and regenerated and wild plants of Valeriana edulis ssp.procera.
AB  - Valepotriate content levels in samples of in vitro cultures of Valeriana edulis
      ssp. procera were compared with those of roots and rhizomes of wild plants in the
      reproductive stage. Rhizomes and roots of regenerated and wild plants showed a
      similar valepotriate content. The data obtained support the hypothesis that
      valepotriate production in V. edulis spp. procera is closely related to rhizome
      and root differentiation. The large-scale propagation of this endangered plant
      may offer an attractive alternative for its production for medicinal purposes.

PMID- 11975505
TI  - Four new flavonol glycosides from the leaves of Astragalus caprinus.
AB  - Four new flavonol 3-O-glycosides were isolated from the leaves of Astragalus
      caprinus. Their structures were elucidated by spectroscopic methods as
      rhamnocitrin-3-O-[3-hydroxy-3-methylglutaroyl(1-->6)][beta-D-apiofuranosyl(1-
      >2)]-beta-D-galactopyranoside (1), rhamnetin-3-O-[3-hydroxy-3-methylglutaroyl(1-
      >6)][beta-D-apiofuranosyl(1-->2)]-beta-D-galactopyranoside (2), kaempferol-3-O
      [beta-D-xylopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1-->6)]-beta-D
      galactopyranoside (3), and quercetin-3-O-[beta-D-xylopyranosyl(1-->3)-alpha-L
      rhamnopyranosyl(1-->6)][beta-D-apiofuranosyl(1-->2)]-beta-D-galactopyranoside
      (4).

PMID- 11975506
TI  - Absolute stereochemistry of ibhayinol from a South African sea hare.
AB  - The absolute stereochemistry of the tricyclic, sesquiterpene ibhayinol (5)
      extracted from the sea hare Aplysia dactylomela, collected in Algoa Bay, South
      Africa, was established as 1S, 3S, 4S, 6R, 7S, 10R, 11S from a single-crystal X
      ray diffraction experiment. The structure of ibhayinol suggested that 8-dehydroxy
      1-deacetylalgoane (7) might be a biosynthetic precursor of this compound.

PMID- 11975507
TI  - Isolation and structures of guaianolides from Carpesium macrocephalum.
AB  - Two new guaianolides, 4alpha,10alpha-dihydroxy-1beta(H),5beta(H)-guai-11(13)-en
      8alpha,12-olide (2) and 4beta,10beta-dihydroxy-5alpha(H)-1,11(13)-guaidien
      8alpha,12-olide (3), from Carpesium macrocephalum were isolated, and their
      structures were elucidated on the basis of spectroscopic studies.

PMID- 11975508
TI  - Plocamenols A-C, novel linear polyhalohydroxylated monoterpenes from Plocamium
      cartilagineum.
AB  - Three new minor linear polyhalohydroxylated marine monoterpenes, plocamenols A-C
      (1-3), have been isolated from the red alga Plocamium cartilagineum. The
      structure and relative stereochemistry of these compounds were determined on the
      basis of spectroscopic evidence.

PMID- 11975509
TI  - New flavones from Millettia erythrocalyx.
AB  - From the stem bark of Millettia erythrocalyx, three new compounds, namely,
      millettocalyxins A-C (1-3), and the new natural product pongol methyl ether (4)
      were isolated, along with 10 other known compounds. The structures of the new
      isolates were elucidated on the basis of spectroscopic data interpretation.

PMID- 11975510
TI  - Ceriopsin E, a new epoxy ent-kaurene diterpenoid from Ceriops decandra.
AB  - A new epoxy ent-kaurene diterpenoid, ceriopsin E (1), has been isolated from the
      mangrove plant Ceriops decandra and its structure elucidated by spectral data and
      single-crystal X-ray analysis.

PMID- 11975511
TI  - 1,2-bis(1H-indol-3-yl)ethane-1,2-dione, an indole alkaloid from the marine sponge
      Smenospongia sp.
AB  - 1,2-Bis(1H-indol-3-yl)ethane-1,2-dione (1), a bisindole alkaloid, was isolated
      from the marine sponge Smenospongia sp. The known compounds indole-3-carbaldehyde
      (2), 6-bromoindole-3-carbaldehyde (3), and tryptamine (4) and mixtures of the
      (Z/E) isomers of 6-bromo-2'-demethylaplysinopsin (5a/5b) and 6-bromo-3'-deimino
      2',4'-bis(demethyl)-3'-oxoaplysinopsin (6a/6b) were also isolated.

PMID- 11975512
TI  - Clathriol, a novel polyoxygenated 14beta steroid isolated from the New Zealand
      marine sponge Clathria lissosclera.
AB  - Clathriol (1), a highly oxygenated steroid with the unusual 14beta configuration,
      was isolated from the New Zealand marine sponge Clathria lissosclera. The
      structure was elucidated from a combination of NMR and mass spectroscopy.
      Clathriol showed in vitro antiinflammatory activity against human neutrophyl and
      rat mast cells.

PMID- 11975513
TI  - Isolation, structure elucidation, and absolute configuration of 26-deoxyactein
      from Cimicifuga racemosa and clarification of nomenclature associated with 27
      deoxyactein.
AB  - A new triterpene glycoside, 26-deoxyactein (1), along with two known compounds,
      23-epi-26-deoxyactein (2), previously designated as "27-deoxyactein", and actein
      (3), were isolated from the roots/rhizomes of Cimicifuga racemosa. The structures
      and absolute stereochemistry of 1 and 2 were established by spectroscopic methods
      (FABMS, (1)H and (13)C NMR) and single-crystal X-ray data analysis.

PMID- 11975515
TI  - Derrisin, a new rotenoid from Derris malaccensis plain and anti-Helicobacter
      pylori activity of its related constituents.
AB  - A new rotenoid, derrisin (1), together with 10 known rotenoids (2-11) were
      isolated from the roots of Derris malaccensis Plain. The structure of 1 was
      elucidated by spectroscopic analysis. Nine of the isolated rotenoids (3-11)
      showed antibacterial activity against Helicobacter pylori.

PMID- 11975514
TI  - Reversal of multidrug resistance by tropane alkaloids from the stems of
      Erythroxylum rotundifolium.
AB  - Six tropane alkaloid esters were isolated from the stems of Erythroxylum
      rotundifolium. The structures of three new tropane esters, 7beta-hydroxy-6beta
      (3,4,5-trimethoxybenzoyloxy)-3alpha-(E)-(3,4,5-trimethoxycinnamoyloxy)tropane
      (1), 6beta-benzoyloxy-3alpha-(Z)-(3,4,5-trimethoxycinnamoyloxy)tropane (2), and (
      )-6beta-benzoyloxy-3alpha-hydroxytropane (3), were established by spectroscopic
      techniques. When alkaloids 1-6 were evaluated against a panel of human cancer
      cell lines, the new compound 6beta-benzoyloxy-3alpha-(Z)-(3,4,5
      trimethoxycinnamoyloxy)tropane (2) and three known compounds, 6beta-benzoyloxy
      3alpha-(3,4,5-trimethoxycinnamoyloxy)tropane (4), 6beta-benzoyloxy-3alpha-(E)
      (3,4,5-trimethoxycinnamoyloxy)tropane-7beta-ol (5), and 7beta-acetoxy-6beta
      benzoyloxy-3alpha-(E)-(3,4,5-trimethoxycinnamoyloxy)tropane (6), demonstrated
      greatest activity with multidrug-resistant oral epidermoid carcinoma (KB-V1)
      cells incubated in the presence of vinblastine. Thus, tropane esters of this type
      can reverse the multidrug-resistance phenotype, presumably by interacting with P
      glycoprotein.

PMID- 11975516
TI  - Efficacy of scopadulcic acid A against Plasmodium falciparum in vitro.
AB  - Scoparia dulcis is a perennial herb widely distributed in many tropical
      countries. It is used as an herbal remedy for gastrointestinal and many other
      ailments, and in Nicaragua extracts are used to treat malaria. Phytochemical
      screening has shown that scopadulcic acid A (SDA), scopadulcic acid B (SDB), and
      semisynthetic analogues are pharmacologically active compounds from S. dulcis.
      SDB has antiviral activity against Herpes simplex virus type 1, antitumor
      activity in various human cell lines, and direct inhibitory activity against
      porcine gastric H(+), K(+)-ATPase. A methyl ester of scopadulcic acid B showed
      the most potent inhibitory activity against gastric proton pumps of 30 compounds
      tested in one study. Compounds with antiviral, antifungal, and antitumor activity
      often show activity against Plasmodium falciparum. In P. falciparum, the plasma
      membrane and food vacuole have H(+)-ATPases and the acidocalcisome has an H(+)
      Ppase. These proton pumps are potential targets for antimalarial therapy and may
      have their function disrupted by compounds known to inhibit gastric proton pumps.
      We tested pure SDA and found in vitro activity against P. falciparum with an
      IC(50) of 27 and 19 microM against the D6 and W2 clones, respectively. The IC(50)
      against the multidrug-resistant isolate, TM91C235, was 23 microM.

PMID- 11975517
TI  - Two new furanoditerpenes from Saururus chinenesis and their effects on the
      activation of peroxisome proliferator-activated receptor gamma.
AB  - Two new acyclic furanoditerpene compounds, saurufuran A (1) and B (2), were
      obtained from the root of Saururus chinensis, and their structures were
      elucidated by means of 1D and 2D NMR spectroscopic analyses. Saurufuran A (1) is
      effective on the activation of peroxisome proliferator-activated receptor gamma
      (PPARgamma) with an EC(50) value of 16.7 microM; however, saurufuran B (2), with
      an EC(50) value of >100 microM, weakly activated the PPARgamma.

PMID- 11975518
TI  - 7-O-6'-O-malonylcachinesidic acid, a new macrocyclic iridoid ester of malonic
      acid from the Tunisian plant Ajuga pseudoiva.
AB  - A new iridoid glucoside, 7-O-6'-O-malonylcachinesidic acid (1), was isolated from
      the leaves of Ajuga pseudoiva and characterized as its triacetyl derivative (1a).
      Its structure was established by spectroscopic methods and showed an unusual
      feature, in which an alcoholic function of the iridoid moiety and the primary
      alcohol of a glucopyranose unit form a 13-membered heterocycle with malonic acid.

PMID- 11975519
TI  - Myxostiolide, myxostiol, and clavatoic acid, plant growth regulators from the
      fungus Myxotrichum stipitatum.
AB  - New plant growth regulators, named myxostiolide (1), myxostiol (2), and clavatoic
      acid (3), have been isolated from Myxotrichum stipitatum, and their structures
      have been established by spectroscopic methods including 2D NMR. The biological
      activities of 1, 2, and 3 have been examined using tea pollen and lettuce
      seedling bioassay methods. With tea pollen, compound 1 inhibited the pollen tube
      growth to 14% of control at a concentration of 100 mg/L. With lettuce seedlings,
      compound 2 accelerated the root growth from 1 mg/L to 100 mg/L and compound 3
      inhibited the root growth, to 52% of control, at a concentration of 100 mg/L.

PMID- 11975520
TI  - A new dimeric dihydrochalcone and a new prenylated flavone from the bud covers of
      Artocarpus altilis: potent inhibitors of cathepsin K.
AB  - A MeOH/CH(2)Cl(2) extract of the bud covers of Artocarpus altilis collected in
      Micronesia showed activity in a cathepsin K inhibition assay. In addition to the
      three known flavonoids isolated from the bud covers of this species, two new
      compounds have been identified whose structures were determined on the basis of
      spectral data. These compounds include a dimeric dihydrochalcone, cycloaltilisin
      6 (2), and a new prenylated flavone, cycloaltilisin 7 (3). Novel compounds 2 and
      3 have IC(50) values of 98 and 840 nM, respectively, in cathepsin inhibition.

PMID- 11975522
TI  - A new biologically active malyngamide from a New Zealand collection of the sea
      hare Bursatella leachii.
AB  - A new malyngamide, S (1), was isolated from a New Zealand collection of the sea
      hare Bursatella leachii and structurally characterized by spectroscopic methods
      and chemical degradation. Malyngamide S exhibited cytotoxicity and
      antiinflammatory properties.

PMID- 11975521
TI  - Haploscleridamine, a novel tryptamine-derived alkaloid from a sponge of the order
      haplosclerida: an inhibitor of cathepsin K.
AB  - As part of a search for novel inhibitors of cathepsin K, the MeOH extract of a
      Micronesian sponge of the order Haplosclerida was shown to be active. Bioassay
      guided fractionation of the extract yielded halitoxins, tryptamine, and a novel
      tryptamine-derived alkaloid, haploscleridamine (1). The tetrahydro-beta-carboline
      structure of haploscleridamine (1) was elucidated through spectral techniques.
      Haploscleridamine (1) was found to be an inhibitor of cathepsin K with an IC(50)
      of 26 microM.

PMID- 11975523
TI  - Unified route to the palmarumycin and preussomerin natural products.
      Enantioselective synthesis of (-)-preussomerin G.
AB  - The total syntheses of eight members of the palmarumycin family have been
      achieved, with identification of the absolute stereochemistry for three of these
      natural products. In addition, the ras-farnesyl transferase inhibitor (-)
      preussomerin G has been synthesized, achieving the first enantioselective route
      for accessing this family of natural products. Highlights of the synthetic work
      include an asymmetric epoxidation of a cyclic enone in excellent yield and
      enantiomeric excess and a potentially biomimetic oxidative spirocyclization for
      the introduction of the bis-spiroketal array unique to the preussomerin natural
      products.

PMID- 11975524
TI  - Total synthesis of (-)-callystatin A.
AB  - A total synthesis of the cytotoxic polyketide marine natural product callystatin
      A is described. The route features chiral allenylmetal additions to construct the
      polypropionate C15-22 segment and an sp(2)-sp(3) Suzuki coupling to join the C1
      C11 and C12-C22 subunits.

PMID- 11975525
TI  - Mechanisms of acid decomposition of dithiocarbamates. 4. Theoretical calculations
      on the water-catalyzed reaction.
AB  - A theoretical study of the water-catalyzed dithiocarbamic acid cleavage has been
      performed using N-methyl- (MeDTC) and N-phenyldithiocarbamic acid (PhDTC) as
      model molecules. Calculations have been carried out within the Density Functional
      Theory (DFT) formalism, using the B3LYP hybrid functional together with medium
      sized basis sets, both in gas phase and by considering solvent effects through
      dielectric continuum methods. According to the results obtained, both in gas
      phase and in solution, MeDTC decomposes through a proton-transfer step assisted
      by a water molecule (this being the rate-determining step), leading to a
      zwitterionic intermediate, followed by a fast N-C bond-breaking process. In the
      case of PhDTC, the theoretical results point to a one-step mechanism in which the
      N-C bond breaking takes place in a concerted manner with the proton transfer. The
      calculated Delta Delta G(++) of the proton-transfer step for MeDTC and PhDTC is
      4.0 kcal mol(-1), which is similar to the experimental values. For both compounds
      the water-assisted intramolecular proton transfer occurs with a twisting of the
      CS(2) group that inhibits the resonance of the thiocarbamic group, making the
      nitrogen more basic and therefore favoring the proton transfer. The difference in
      the torsional barrier has been calculated to be ca. 5 kcal mol(-1), and it is
      therefore concluded that most of the activation barrier of the reaction is due to
      the torsional barrier of the CS(2) group.

PMID- 11975526
TI  - Solvent-dependent dynamic kinetic asymmetric transformation/kinetic resolution in
      molybdenum-catalyzed asymmetric allylic alkylations.
AB  - Catalytic asymmetric alkylation reactions of branched racemic carbonates 1a and
      1b with sodium dimethyl malonate, promoted by molybdenum and ligand 5, proceed by
      a kinetic resolution in toluene, THF, tetrahydropyran, i-PrOAc, 1,2
      dichloroethane, and MeCN with k(rel) of 7-16. In THF, MeCN, tetrahydropyran, and
      i-PrOAc using the (S,S)-5 ligand, the fast reacting (S)-carbonate enantiomer
      provides the branched product with high ee (97-99.5%) and branched/linear
      selectivity, but the ee erodes as the reaction of the slow-reacting (R)
      enantiomer takes place. This implies that the rate of equilibration of the
      oxidative addition complexes in these solvents is competitive with the subsequent
      malonate displacement step. In toluene and dichloroethane, the ee and
      branched/linear ratios diminish during the reaction of the slow-reacting (R)
      isomer, but not nearly as much as in the other solvents. This is most likely due
      to either an increase in the rate of equilibration of the oxidative addition
      complexes relative to the malonate displacement step, or vice versa. Because of
      the minimal stereochemical memory effect in toluene and 1,2-dichloroethane, the
      reactions in these solvents can be carried to completion (dynamic kinetic
      asymmetric transformation) and still provide product with excellent ee (>95%).
      The anion of dimethyl methylmalonate also reacts via a kinetic resolution,
      although the ee's, rates, and k(rel) values differ from those of the reactions
      with dimethyl malonate.

PMID- 11975527
TI  - A new atropisomeric P,N ligand for rhodium-catalyzed asymmetric hydroboration.
AB  - A new optically active and large dihedral angle atropisomeric P,N ligand, pyphos,
      which contains a tertiary phosphine and pyridine moiety, was prepared and
      resolved through diastereomeric complexation with chiral palladium amine
      complexes. The hexafluorophosphate salt of the diastereomers were found to be
      separable by fractional recyrstallization, while the corresponding chloride salt
      did not. [Rh(COD)pyphos]PF(6) complex was synthesized by metalation of pyphos
      with [Rh(COD)Cl](2) followed by anion exchange with NH(4)PF(6) in excellent
      yield, and the target rhodium complex was characterized by single-crystal X-ray
      crystallography. The chiral cationic rhodium complex was utilized in the
      enantioselective hydroboration of vinylarenes. Excellent regioselectivity and
      good enantioselectivity were observed, and the ee values were found to be
      dependent on the electronic properties of para-substituted styrenes.

PMID- 11975528
TI  - Cyclization/hydrosilylation of functionalized 1,6-diynes catalyzed by cationic
      platinum complexes containing bidentate nitrogen ligands.
AB  - A 1:1 mixture of the platinum dimethyl diimine complex [PhN[double
      bond]C(Me)C(Me)[double bond]NPh]PtMe(2) (4a) and B(C(6)F(5))(3) catalyzed the
      cyclization/hydrosilylation of dimethyl dipropargylmalonate (1) and HSiEt(3) to
      form 1,1-dicarbomethoxy-3-methylene-4-(triethylsilylmethylene)cyclopentane (3) in
      82% isolated yield with 26:1 Z:E selectivity. Platinum-catalyzed diyne
      cyclization/hydrosilylation tolerated a range of functional groups including
      esters, sulfones, acetals, silyl ethers, amides, and hindered ketones. Diynes
      that possessed propargylic substitution underwent facile
      cyclization/hydrosilylation to form silylated 1,2-dialkylidene cyclopentanes as
      mixtures of regioisomers. Diynes that possessed an electron-deficient internal
      alkyne underwent cyclization/hydrosilylation in moderate yield to form products
      resulting from silyl transfer to the less substituted alkyne. The silylated 1,2
      dialkylidenecyclopentanes formed via diyne cyclization/hydrosilylation underwent
      a range of transformations including protodesilylation, Z/E isomerization, and [4
      + 2] cycloaddition with dieneophiles.

PMID- 11975529
TI  - Diastereoselective synthesis and estimation of the conformational flexibility of
      6-oxoperhydropyridazine-3-carboxylic acid derivatives.
AB  - alpha,beta-Didehydroglutamates have been diastereoselectively transformed into 6
      oxoperhydropyridazine-3-carboxylic acid derivatives (OPCAs), which constitute a
      new class of cyclic amino acid derivatives. Acylation at N-1 renders dipeptides
      which show considerable conformational rigidity. Semiempirical calculations
      suggest that OPCAs might force peptide turns with different amplitudes depending
      on the substitution pattern and relative stereochemistry of the substituents of
      the pyridazinone ring.

PMID- 11975530
TI  - Structural and electronic characteristics of thienyl(aryl)iodonium triflates.
AB  - A general strategy toward the synthesis of aryliodonium triflate salts has been
      exploited to afford derivatives that incorporate thiophene and bithiophene
      components. Both mono- and bis(iodonium) salts have been realized, and a series
      of bithienyl(aryl)iodonium triflates with increasingly electron-withdrawing
      substituents on the aryl moiety have been synthesized. X-ray crystallographic
      analysis of four derivatives (4a, 4b, 6b, and 8c) demonstrates that the solid
      state organization of these salts incorporates extensive networks of secondary
      bonding interactions between the cationic iodonium centers and the triflate
      counterions. UV-vis spectroscopic analysis shows that the electronic interactions
      between pendent aryl and heteroaryl groups across the iodonium center can be
      dictated by substitution. Furthermore, the energy of the HOMO-LUMO gap decreases
      substantially in weakly or noncoordinating solvents.

PMID- 11975531
TI  - Study of cross-conjugated iso-polytriacetylenes and related oligoenynes.
AB  - Two series of monodisperse cross-conjugated oligomers based on enyne repeat units
      have been realized. The first class of molecules, iso-polytriacetylenes (iso
      PTAs, 2), was divergently synthesized using an iterative sequence of palladium
      catalyzed cross-coupling reactions of vinyl triflate 5 with terminal alkynes. The
      second series of oligoenynes (17-20) are based on an octatetrayne backbone, and
      result from homocoupling of the differentially protected iso-PTA oligomers 8-11.
      The longest member of this series, 20, spans ca. 5.6 nm from Si atom to Si atom
      and is composed of a contiguous sequence of 44 sp and sp(2) carbons. The lowest
      energy electronic absorption band for iso-PTA dimers in the progression 13 --> 9 
      -> 16 is consistently red-shifted as a result of extending the cross-conjugated
      structure. A similar comparison within each series (i.e., 16, 6-7, or 17-20),
      however, suggests little effect on the electronic characteristics of these
      molecules as oligomer length is increased. The solid-state properties of one
      derivative, 17, are also described.

PMID- 11975532
TI  - Stereochemical control of reductions. 9. Haptophilicity studies with 1,1
      disubstituted 2-methyleneacenaphthenes.
AB  - A series of 1-methyl-2-methyleneacenaphthenes has been synthesized, bearing an
      additional variable substituent (R) at the 1-position. These compounds have been
      hydrogenated in ethanol over a 5% Pd/C catalyst under standardized conditions in
      order to assess the haptophilicity of R, its ability to enforce addition of
      hydrogen from its own face of the molecule by coordination to the catalyst
      surface. The order of decreasing haptophilicity, assessed as the product epimer
      ratio, for the groups studied was R = CH(2)NH(2), CH(2)NMe(2), CH(2)OH, CHNOH,
      CH(2)OMe, CHO, CONH(2), CH(2)NHCOMe, COOK, COMe, CN, CONHOH, COOH, COOMe, COONa,
      COOLi. Because knowledge of group haptophilicities offers potential for
      stereochemical control in such reductions, comparisons are provided with
      haptophilic orders found in other molecular systems. It is shown that absolute
      haptophilicities can be manipulated by varying the dielectric constant of the
      solvent employed.

PMID- 11975533
TI  - A new approach to the reduction of sulfoxides to sulfides with 1,3-dithiane in
      the presence of electrophilic bromine as catalyst.
AB  - A new, mild, and novel method is described for the efficient deoxygenation of
      sulfoxides to their corresponding sulfides with 1,3-dithiane at room temperature
      in the presence of catalytic amounts of N-bromosuccinimide (NBS), 2,4,4,6
      tetrabromo-2,5-cyclohexadienone (TABCO), or Br(2) as the source of electrophilic
      bromine.

PMID- 11975534
TI  - Chiral Lewis acid catalyzed resolution of racemic enol ester epoxides. Conversion
      of both enantiomers of an enol ester epoxide to the same enantiomer of acyloxy
      ketone.
AB  - This paper describes an efficient kinetic resolution of racemic enol ester
      epoxides via a chiral Lewis acid catalyzed rearrangement. Both enantiomerically
      enriched enol ester epoxides and alpha-acyloxy ketones can be obtained through
      this resolution. A positive nonlinear effect is observed in this process. By
      taking advantage of the mechanistic duality in acid-catalyzed enol ester epoxide
      rearrangement, we can completely convert a racemic enol ester epoxide into an
      enantiomerically enriched alpha-acyloxy ketone by treatment with a catalytic
      amount of a chiral Lewis acid followed by a catalytic amount of an achiral protic
      acid.

PMID- 11975535
TI  - Control of regioselectivity in Pd(0)-catalyzed coupling-cyclization reaction of 2
      (2',3'-allenyl)malonates with organic halides.
AB  - The regioselectivity in the Pd(0)-catalyzed coupling-cyclization of 2-(2',3'
      allenyl)malonates with organic halides is determined by the steric and electronic
      effects of both substrates. By deliberate control of the reaction conditions, the
      regioselectivity of this reaction can be tuned. With conditions A and B, the
      reaction afforded vinylic cyclopropane derivatives, while with conditions C and
      D, the reaction afforded cyclopentene derivatives in a highly selective manner.
      Under similar conditions, 1-alkenyl halides tend to form more three-membered
      cyclic products. The increased steric hindrance at the 2'-position of the allene
      moiety and aryl halides favors the formation of five-membered cyclic products.
      The regioselectivity of the reaction may be explained by the comparison of the
      relative stabilities of syn- and anti-type pi-allyl palladium intermediates.

PMID- 11975536
TI  - Exploring the active site of amine:pyruvate aminotransferase on the basis of the
      substrate structure-reactivity relationship: how the enzyme controls substrate
      specificity and stereoselectivity.
AB  - An active site model of the amine:pyruvate aminotransferase (APA) from Vibrio
      fluvialis JS17 was constructed on the basis of the relationship between substrate
      structure and reactivity. Due to the broad substrate specificity of the APA,
      various amino donors (chiral and achiral amine, amino acid, and amino acid
      derivative) and amino acceptors (keto acid, keto ester, aldehyde, and ketone)
      were used to explore the active site structure. The result suggested a two
      binding site model consisting of two pockets, one large (L) and the other small
      (S). The difference in the size of each binding pocket and strong repulsion for a
      carboxylate in the S pocket were key determinants to control its substrate
      specificity and stereoselectivity. The L pocket showed dual recognition mode for
      both hydrophobic and carboxyl groups as observed in the side-chain pockets of
      aspartate aminotransferase and aromatic aminotransferase. Comparison of the model
      with those of other aminotransferases revealed that the L and S pockets
      corresponded to carboxylate trap and side-chain pocket, respectively. The active
      site model successfully explains the observed substrate specificity as well as
      the stereoselectivity of the APA.

PMID- 11975537
TI  - Mechanism of the second sulfenylation of indole.
AB  - Sulfenylation of indole using a sulfenyl chloride occurs initially at the 3
      position of the ring, leading to a 3-indolyl sulfide. When an excess of sulfenyl
      chloride is used, a second sulfide group is introduced at the 2-position, and an
      indolyl 2,3-bis-sulfide results. We have demonstrated that this second
      sulfenylation occurs not by direct introduction of the second sulfide at the 2
      position but via initial formation of an indolenium 3,3-bis-sulfide intermediate,
      followed by migration of one of the sulfide groups to the 2-position. This was
      achieved by the isolation of two examples of 3H-indole 3,3-bis-sulfides and by
      subsequent demonstration that they rearrange to the indolyl 2,3-bis-sulfides by
      treatment with sulfenyl halides.

PMID- 11975538
TI  - Preparation, properties, and chemical reactivity of alpha-nitrosulfoximines,
      chiral analogues of alpha-nitrosulfones.
AB  - Racemic N-methyl-S-(nitromethyl)-S-phenylsulfoximine (2) was prepared in 87%
      yield via alkaline nitration of N,S-dimethyl-S-phenylsulfoximine. Optically
      active N-methyl-S-(nitromethyl)-S-phenylsulfoximine (both enantiomers) was
      prepared in similar fashion. Reaction of racemic 2 with p-chlorophenyl isocyanate
      and a catalytic quantity of triethylamine in the presence of furan afforded
      dihydrofuroisoxazole 5, the product of nitrile oxide cycloaddition, in 42% yield
      (65:35 diastereomer ratio). Reaction of the dihydrofuroisoxazole 5 with
      phenyllithium and methyllithium afforded replacement of the sulfoximine group by
      phenyl and methyl, respectively. Reaction of racemic 2 with aromatic isocyanates
      and potassium carbonate afforded C-acylation products in 70-78% yield which
      existed as the ylide tautomers 9a,b. Methylation of racemic 2 afforded the C
      alkylate N-methyl-S-(1-nitroethyl)-S-phenylsulfoximine (13), existing as the
      neutral tautomer.

PMID- 11975539
TI  - Preparation of a 24-nor-1,4-dien-3-one triterpene derivative from betulin: a new
      route to 24-nortriterpene analogues.
AB  - A new route to 24-nortriterpene derivatives with 2-hydroxy-Delta(1,4)
      cyclohexadien-3-one A-rings from triterpene precursors has been demonstrated
      beginning with betulin to prepare derivatives of betulinic acid. The key steps in
      the transformation are a Suarez cleavage of the A-ring with a subsequent SmI(2)
      mediated pinacol-type coupling to reclose the A-ring following removal of the C
      24 carbon by oxidative cleavage.

PMID- 11975540
TI  - Total synthesis of spicamycin.
AB  - The first total synthesis of one of the spicamycin congeners, SPM VIII (3), is
      described. A preliminary model study for construction of the characteristic N
      glycoside linkage in spicamycin using tetra-O-benzyl-beta-D-mannopyranosylamine
      (13) and halopurines 5 revealed that Pd-catalyzed conditions successfully
      provided the coupling products 14 and 15 in good yields. It was also shown that
      thermal anomerization of the N-glycosides easily occurred, which resulted in the
      predominant formation of the beta-anomer as the thermodynamically favored
      compound, and the activation energy of anomerization of 15 was estimated to be
      ca. 30 kcal/mol. The novel aminoheptose unit of spicamycin 6 was prepared
      stereoselectively by carbon elongation of an acyclic aldehyde, prepared by ring
      cleavage reaction of a highly functionalized cyclohexane derived from naturally
      abundant myo-inositol. The Pd-catalyzed coupling reaction of the beta
      heptopyranosylamine 6 with protected 6-chloropurine 5d, followed by deprotection,
      provided spicamycin amino nucleoside 2, whose condensation with dodecanoylglycine
      completed the total synthesis of 3. This study confirmed the proposed unique
      structure of a novel nucleoside antibiotic.

PMID- 11975541
TI  - Unusual regioselective intramolecular Diels-Alder reaction forming
      tricyclo[4.3.1.0(3,7)]decane system.
AB  - The intramoleculae Diels-Alder reaction of cyclohexenone having an unsaturated
      ester side chain afforded tricyclo[4.3.1.0(3,7)]decanone in both a regio- and
      stereoselective manner under TMSCl-NEt(3)-ZnBr(2) conditions. Unexpectedly, the
      regiochemical control was against the conventional orbital requirement.

PMID- 11975542
TI  - Nitrile anions: solvent-dependent cyclizations.
AB  - Extensive cyclizations in hydrocarbon and polar solvents demonstrate a profound
      solvent sensitivity for intramolecular nitrile anion alkylations. S(N)i
      cyclizations enforce very precise steric constraints in the transition state,
      allowing correlation of the cyclization stereochemistry with the orbital
      orientation of the nitrile anion. Collectively the cyclizations suggest a
      continuum of nitrile anion transition states, varying from planar to fully
      pyramidal, that selectively cyclize to cis- and trans-decalins, respectively.

PMID- 11975543
TI  - Lewis acid promoted cyclization of enyne triesters and diesters.
AB  - Reactions of enynes with three or two ester groups (1-4) in the presence of
      halogen-ligand Lewis acids gave cyclized products with halide incorporation (5-8)
      with high generality. The cyclization process was also analyzed in a theoretical
      study. Facile isomerization and dehydrohalogenation of five-membered products 5
      and 8 by Al(2)O(3) or Et(3)N were also observed; this process introduces
      conjugated moieties into the products.

PMID- 11975544
TI  - A facile synthesis of enantiopure 2-aziridinesulfinimines and their highly
      diastereoselective reactions with phosphite anions.
AB  - Two novel enantiopure 1-benzyl-2-aziridinesulfinimines bearing a chiral group on
      both sides of the carbon-nitrogen double bond were synthesized from the
      condensation of racemic 1-benzyl-2-aziridinecarboxaldehyde and enantiopure p
      toluenesulfinamide. The addition reaction with phosphite anion followed by the
      ring-opening reaction with thiophenol provided chiral alpha,beta-diamino
      phosphonic acid derivatives. The addition reactions showed the operation of a
      double-stereodifferentiation effect. The possible transition states of the
      reaction were proposed, and high diastereoselectivities of the addition reactions
      of phosphite anions to both aziridinesulfinimines were realized in the presence
      or absence of zinc bromide.

PMID- 11975545
TI  - Syntheses and bioactivities of substituted 9,10-dihydro-9,10
      [1,2]benzenoanthracene-1,4,5,8-tetrones. Unusual reactivities with amines.
AB  - A number of substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrones
      have been synthesized and their anticancer and antimalarial activities evaluated.
      A one-pot synthesis of 2,5,8-trimethoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene
      1,4-dione (4) was achieved by heating a mixture of 1,4-dimethoxyanthracene,
      methoxyhydroquinone, silver oxide, and zinc iodide in toluene. Regioselective
      bromination of 4 and 2-methoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8
      tetrone (7) with N-bromosuccinimide provided 2-bromo-3,5,8-trimethoxy-9,10
      dihydro-9,10-[1,2]benzenoanthracene-1,4-dione and 2-bromo-3-methoxy-9,10-dihydro
      9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone (1), respectively. The reactions of 1
      with aliphatic primary amines and secondary amines, respectively, produced
      different products, a result most likely attributed to the different basicities
      (or nucleophilicities) and steric effects of the two kinds of amines. The
      structure of the displacement product, 2-bromo-3-[2-(tert
      butoxycarbonyl)ethylamino]-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8
      tetrone, from the reaction of 1 with tert-butyl 3-aminopropanoate was
      unequivocally determined by a single-crystal X-ray analysis. IC(50) values of
      triptycene bisquinones for the inhibition of L1210 leukemia cell viability are in
      the 0.11-0.27 microM range and for the inhibition of Plasmodium falciparum 3D7
      are in the 4.7-8.0 microM range.

PMID- 11975546
TI  - DFT study of substituted and benzannelated aryl cations: substituent dependency
      of singlet/triplet ratio.
AB  - By using density functional theory (DFT) method at the B3LYP/6-311+G level, it
      has been shown that the preference for the singlet-state phenyl cation can be
      dramatically increased relative to the triplet state by introducing onium
      cationic substituents in the para position. At this level of theory, the singlet
      ground state for the parent phenyl cation was found to be lower than the triplet
      by 19.6 kcal/mol. Introduction of electron-donating substituent groups, namely 
      NMe(2), -NH(2), and -SMe in the para position, strongly favors the triplet state.
      The -OMe and -SH groups cause a similar but smaller effect, whereas -OH
      substitution results in an energetically identical system. Protonation of these
      substituent groups form onium-phenyl dications for which a complete reversal of
      the relative stabilities in favor of the singlet ground state are indicated with 
      SH(2)(+), -SMeH(+), and -NH(3)(+) showing the largest singlet/triplet energy
      difference. The -N(2)(+) group in the para position has a similar effect.
      Benzannelation also increases the relative stability of triplet aryl cation.
      Whereas the 1-naphththyl and 2-naphthyl cations are energetically identical, in
      the 9-anthracenyl cation the triplet minimum lies 13.4 kcal/mol below the singlet
      minimum. Introduction of activating groups, i.e., OH and NMe(2) at the 4-position
      of the 1-naphthyl cation, greatly increases the relative stability of the triplet
      state. Upon heteroatom protonation, the singlet/triplet energy gap is
      substantially narrowed but the triplet state still remains lower in energy.
      Structural features in the resulting dications are discussed and compared with
      the corresponding monocations. The NBO charges at the cationic centers were also
      compared. We have also calculated the dediazoniation and decarbonylation
      energetics for mono- and bis-o-trimethylsilyl-substituted benzenediazonium and
      benzoyl cation to aryl cations in order to probe the effect of beta-silyl
      stabilization of the positive charge.

PMID- 11975547
TI  - Cyclic vinyl p-tolyl sulfilimines as chiral dienophiles: Diels-Alder reactions
      with furan and acyclic dienes.
AB  - The dienophilic behavior of the sulfilimine 2, synthesized from (Z)-3-p
      tolylsulfinylacrylonitrile 1, in its Diels-Alder reactions with furan and acyclic
      dienes has been investigated. A complete pi-facial selectivity for 2, opposite to
      that observed from its precursor 1, is the main feature of all these
      cycloadditions. Moreover, the high exo selectivity observed in reactions of 2
      with furan (not observed for 1) contrasts with the almost complete endo
      selectivity with other cyclic and acyclic dienes. Additionally, the opposite
      regioselectivities obtained for 2 with Dane's diene and 1-substituted butadienes
      (not observed for 1) are also noteworthy. This behavior allows dienophiles 1 and
      2 to be considered as complementary precursors from a synthetic point of view.

PMID- 11975548
TI  - Cyclic vinyl p-tolyl sulfilimines as chiral dienophiles: theoretical study on the
      stereoselectivity, Lewis acid catalysis, and solvent effects in their Diels-Alder
      reactions.
AB  - The theoretical study reported in the present work deals with chiral cyclic vinyl
      sulfilimines and their reactivity as dienophiles in [4 + 2] cycloaddition
      reactions, using B3LYP/6-31G(d)//AM1 and B3LYP/6-31G(d)//B3LYP/6-31G(d) model
      chemistries. Consideration of Lewis acid catalysis, illustrated by BF(3),
      decreases the activation energies of the cycloaddition process while the charge
      transfer from the diene to the sulfilimine is augmented. The [4 + 2]
      cycloaddition reactions of sulfilimines with both furan and cyclopentadiene occur
      in the gas phase with endo stereoselectivity, which is more pronounced with the
      latter diene. Endo-exo energy differences in the gas phase with the B3LYP/6
      31+G(d)//B3LYP/6-31+G(d), B3LYP/6-31G(d)//B3LYP/6-31G(d), and B3LYP/6-31G(d)//AM1
      model chemistries are almost the same. Solvent effects are responsible for the
      inversion of the stereoselectivity in the reactions of sulfilimines with furan
      because of the great difference in the dipole moments in endo and exo approaches.

PMID- 11975549
TI  - Studies on the formation and incorporation of streptolidine in the biosynthesis
      of the peptidyl nucleoside antibiotic streptothricin F.
AB  - Streptothricin F (STF, 1) is a peptidyl nucleoside antibiotic produced by
      Streptomyces lavendulae. Studies were conducted to address the formation and
      timing of incorporation of the arginine-derived base streptolidine (4) during the
      biosynthesis of 1. [guanidino-(13)C]Streptolidine (10) was prepared by
      modification of an established method and used in whole-cell incorporation
      experiments. Analysis of the purified STF by (13)C NMR revealed a 1.9% enrichment
      of the guanidino carbon, confirming 4 as an advanced precursor to 1 and
      supporting proposals that 1 is assembled via a convergent biosynthetic pathway.
      To identify advanced intermediates in the conversion of L-arginine to 4, (2S,3R)
      [guanidino-(13)C]capreomycidine (32) was prepared from oxazolidine aldehyde (18)
      via 1,1-dimethylethyl (4R,1'S)-4-(1',3'-diaminopropyl)-2,2-dimethyl-3
      oxazolidinecarboxylate (30). Treatment of 30 with Br(13)CN yielded the
      corresponding diprotected amino alcohol, which was readily converted to 32. The
      STF isolated from whole-cell incorporation experiments with 32 showed no
      significant (13)C enrichment at the guanidino carbon. These results suggest that
      32 may be an enzyme-bound intermediate, unable to enter the cell, or is not a
      precursor to STF.

PMID- 11975550
TI  - Electronic effects in the N-nitrosation of N-benzylpivalamides.
AB  - A series of N-4-R-benzylpivalamides (R = MeO, Me, H, CF(3), and NO(2)) was
      nitrosated using a standardized solution of N(2)O(4) in CDCl(3) at -40 degrees C.
      The reactions, which produced the corresponding N-4-R-benzyl-N
      nitrosopivalamides, were followed by (1)H NMR spectroscopy. The rate of
      nitrosation was found to vary in a systematic way with the nature of the 4-R
      group on the aromatic ring. Thus, electron-releasing groups increased the rate of
      the reaction, whereas electron-withdrawing ones decelerated N-nitrosation. In a
      similar fashion, the nitrosations were accelerated in polar solvents but were
      slower in solvents of low polarity. The sensitivities of N-nitrosation to these
      intra- and intermolecular electronic effects are compared to those from a
      previous study examining the dependence of the kinetics of nitrosoamide
      thermolyses on the same factors.

PMID- 11975551
TI  - Host-guest interactions between beta-cyclodextrin and the (Z)-phenylhydrazone of
      3-benzoyl-5-phenyl-1,2,4-oxadiazole: the first kinetic study of a ring-ring
      interconversion in a "confined environment".
AB  - The effect of beta-cyclodextrin (beta-CD) on the mononuclear heterocyclic
      rearrangement of the (Z)-phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole
      (1) in aqueous borate buffer at pH = 9.6 has been analyzed at temperatures
      ranging from 293.15 to 313.15 K. The trend of the absorption spectra of 1 as a
      function of time has been accounted for with the formation of two different 1:1
      complexes between beta-CD and 1, the first, "unreactive" complex being formed
      faster than the "reactive" one. The occurrence of negative activation enthalpy
      values for the studied interconversion evidences the kinetic relevance of
      inclusion processes. Computational models elaborated using the MM2 molecular
      mechanics force field give an idea of the relative importance of the different
      complexes, additionally helping us to formulate a suitable reaction scheme.

PMID- 11975552
TI  - Total synthesis of (S)-(+)-imperanene. Effective use of regio- and
      enantioselective intramolecular carbon-hydrogen insertion reactions catalyzed by
      chiral dirhodium(II) carboxamidates.
AB  - The total synthesis of (S)-(+)-imperanene, a natural product found in Chinese
      medicine, has been completed in 12 steps from a commercially available cinnamic
      acid. The key step is highly enantioselective carbon-hydrogen insertion from a
      diazoacetate using a chiral dirhodium(II) carboxamidate catalyst. An elimination
      process essential to the construction has been optimized to avoid intramolecular
      Friedel-Crafts alkylation.

PMID- 11975554
TI  - Role of NaBH(4) stabilizer in the oxazaborolidine-catalyzed asymmetric reduction
      of ketones with BH(3-)THF.
AB  - When stabilized BH(3-)THF (BTHF) was added to a mixture of ketone and tetrahydro
      1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole (MeCBS
      ozaxaborolidine, MeCBS) catalyst 1, low enantioselectivities resulted. Several
      relative rate experiments showed that a borohydride species in BTHF catalyzed the
      nonselective borane reduction of ketones, effectively competing with
      enantioselective MeCBS reduction of ketones, lowering the overall selectivity of
      the reaction. Improved enantioselectivities in the reaction are obtained by
      reversing the mode of addition (ketone to BTHF and catalyst), lowering the
      concentration of NaBH(4) stabilizer in the BTHF solution (87-95% ee) and
      increasing the concentration or addition rate of BTHF. Decreased reaction
      temperature and increased catalyst loading only slightly improved the selectivity
      of the reaction. Upon reaction parameter optimization, simultaneous addition of
      substrate and BTHF to MeCBS catalyst stabilizer resulted in the highest overall
      enantioselectivities (96% ee) and diminished the effect of the borohydride.
      Alternatively, the addition of Lewis acids such as BF(3-)THF to the reaction
      mixture effectively destroyed the NaBH(4) stabilizer in BTHF solutions, restoring
      the enantioselectivity to acceptable levels.

PMID- 11975553
TI  - A solid-phase synthetic route to unnatural amino acids with diverse side-chain
      substitutions.
AB  - Reacting imine derivatives of resin-bound amino acids with alpha,omega
      dihaloalkanes provides highly versatile intermediates to racemic alpha,alpha
      disubstituted amino acids with a wide variety of side-chain functionality. Two
      strategies were developed to convert the intermediate omega-chloro or omega-bromo
      derivatives to the desired products. Together, they allow the creation of amino
      acids with diverse functionalities (omega-chlorides, nitriles, azides, acetates,
      thioacetates, thioethers, secondary and tertiary aliphatic amines, and anilines)
      placed at varying chain lengths (2-5) from the alpha-center of the amino acid.

PMID- 11975556
TI  - Stereocontrol at the steady state in radical cyclizations of acyclic dihalides.
AB  - The first examples of manipulating stereocontrol solely by reaction topography in
      radical cyclizations starting from acyclic precursors are reported. The kinetic
      model for acyclic compound stereoselection is verified experimentally by
      conducting a series of radical cyclizations of 1,3-dihalo-2-(1-phenyl-3
      butynyl)propanes with triphenyltin hydride and measuring the ratios of the
      products. Monohalide intermediates are observed for the first time, and evidence
      that bromide- and iodide-substituted radicals have different cyclization rate
      constants is provided.

PMID- 11975555
TI  - Tricycloclavulone and clavubicyclone, novel prostanoid-related marine oxylipins,
      isolated from the Okinawan soft coral Clavularia viridis.
AB  - Two novel prostanoid-related marine oxylipins, tricycloclavulone (1) and
      clavubicyclone (2), were isolated from the Okinawan soft coral Clavularia
      viridis. The structures of 1, having a tricyclo[5.3.0.0(1,4)]decane ring system,
      and 2, having a bicyclo[3.2.1]octane ring system, were elucidated on the basis of
      spectroscopic analysis. Clavubicyclone showed a moderate growth inhibition
      activity against tumor cells in vitro.

PMID- 11975557
TI  - Allylation of exocyclic N-Acyliminium ions generated from chiral N-[1
      (phenylsulfonyl)alkyl]oxazolidin-2-ones.
AB  - N-[1-(Phenylsulfonyl)alkyl]oxazolidin-2-ones are successfully prepared by
      condensation of the corresponding optically active oxazolidin-2-ones with
      aldehydes and benzenesulfinic acid. At low temperature, in the presence of
      titanium tetrachloride, these sulfones are converted into N-acyliminium ions,
      which react with allyltrimethylsilane with a variable degree of
      stereoselectivity. The best results are obtained with (R)-5,5-dimethyl-4
      phenyloxazolidin-2-one as a chiral auxiliary. Cleavage of the oxazolidin-2-one
      ring with lithium/ammonia affords the corresponding homoallylamines, which reveal
      an absolute configuration opposite that expected on the basis of the usual steric
      effects. A complexation of the Lewis acid with the N-acyliminium ion may be
      responsible of this rather unusual stereochemical outcome.

PMID- 11975558
TI  - Synthesis of alpha-GalNAc thioconjugates from an alpha-GalNAc mercaptan.
AB  - A variety of functionalized thioglycosides and other derivatives (10-24) of 2
      acetamido-2-deoxy-1-thio-alpha-D-galactopyranose have been prepared in good
      yields and with high anomeric purities by S-substitution reactions of the sulfide
      anion or sulfur-centered radical from mercaptan 6. Given the importance in nature
      of the alpha-GalNAc 1-O-linkage, and the greater chemical and biological
      stability of the corresponding 1-S-linkage, these thioconjugates may find
      application in studies of synthetic vaccines, enzyme inhibitors, glycomimetic
      scaffolds, and other complex carbohydrate systems.

PMID- 11975559
TI  - Diastereoselective reactions of delta-oxy-substituted allylic acetates with
      organocopper reagents.
AB  - S(N)2' (gamma) substitutions of delta-substituted allylic acetates with Grignard
      reagents and copper catalysts proceed with high diastereoselectivities. With
      benzyloxy, methoxymethoxy, and tert-butyldimethylsiloxy groups, reactions favor
      the anti-isomer with selectivities up to anti:syn = >99:1. With a hydroxyl group,
      selectivities are reversed and the syn-isomer is favored with selectivities up to
      anti:syn = <1:99.

PMID- 11975561
TI  - Synthesis of optically active vicinal fluorohydrins by lipase-catalyzed
      deracemization.
AB  - Three microbial lipases have been used to deracemize trans-2-fluorocycloalkanols
      2 both by hydrolysis of the corresponding acetates 3 or chloroacetates 4 and by
      esterification of the fluorohydrins 2 using vinyl acetate and vinyl
      chloroacetate, respectively. Pseudomonas cepacia lipase was the most selective
      for the six- and the seven-membered-ring compounds, while the lipase from Candida
      rugosa was most useful for the eight-membered-ring compounds. Both lipases
      transform the (R)-enantiomers preferentially. In contrast the lipase from Candida
      antarctica hydrolyzed the esters of trans-2-fluorocyclohexanol 2a and esterified
      the fluorohydrin itself with very low enantiopreference for the (R)-isomers. The
      seven- and the eight-membered ring esters and the corresponding fluorohydrins
      were also transformed with low, but reverse, enantioselectivity.

PMID- 11975560
TI  - Cross-linking of proteins by 3-(trifluoromethyl)-2,5-hexanedione. Model studies
      implicate an unexpected amine-dependent defluorinative substitution pathway
      competing with pyrrole formation.
AB  - Protein modification by the neurotoxic gamma-diketone 3-methyl-2,5-hexanedione (3
      MHD) and its analogue 3-(trifluoromethyl)-2,5-hexanedione (3-TFMHD) was examined.
      Unlike 3-MHD, which forms lysine-based pyrroles that lead to autoxidation
      dependent protein cross-linking, 3-TFMHD forms an autoxidatively inert pyrrole.
      The surprising finding that 3-TFMHD was nonetheless as effective as 3-MHD in
      cross-linking ribonuclease A suggested that protein lysine condensation with 3
      TFMHD could take an alternate course competing with pyrrole formation. Model
      studies using neopentylamine led to the isolation of the expected 1-(2,2
      dimethylpropyl)-2,5-dimethyl-3-(trifluoromethyl)pyrrole as well as the
      neopentylamine-3-TFMHD 2:1 adducts N,N'-bis(2,2-dimethylpropyl)-2-amino-3-acetyl
      5-methylpyrrole (major) and N,N'-bis(2,2-dimethylpropyl)-3-(1-aminoethylidene)-5
      methyl-4-pyrrolin-2-one (minor). The formation of these 2:1 adducts, the lysine
      analogues of which are believed to be mainly responsible for the observed protein
      cross-linking, is proposed to proceed via Schiff base formation, enamine fluoride
      elimination, second amine condensation, and hydrolysis.

PMID- 11975562
TI  - Selectivity of biohydroxylation with Beauveria bassiana of trans-2
      fluorocycloalkyl N-phenylcarbamates.
AB  - Biohydroxylation with Beauveria bassiana of racemates and the pure enantiomers of
      trans-2-fluorocyclohexyl- 3 and trans-2-fluorocycloheptyl N-phenylcarbamates 6
      were investigated and compared with results found for the corresponding
      nonfluorinated parent compounds. In all cases, mixtures of diastereomeric
      products hydroxylated in the 4-position were isolated, besides products of p
      hydroxylation of the aromatic ring and succeeding compounds derived from these
      primary reaction products. The regioselectivity of hydroxylation by this fungus
      is not changed by a single fluorine substituent attached closely to the electron
      rich anchoring group in the trans-2-position. There is a different influence on
      the diastereoselectivity of hydroxylation depending on the absolute configuration
      of the fluorinated substrates. While the transformation of the (S,S)-2
      fluorocycloalkyl N-phenylcarbamates is not diastereoselective giving almost 1:1
      mixtures of cis- and trans-4-hydroxyl compounds, the corresponding reactions of
      the (R,R)-isomers led preferentially to the products trans-hydroxylated in the 4
      position. The transformation of the racemic fluorinated six-membered N
      phenylcarbamate 3 led to products having a very small enantiomeric excess. The
      fluorine substituent slightly increased the enantioselectivity of transformation
      of the racemic seven-membered substrate 6 compared to the C(s)()-symmetric
      nonfluorinated carbamate. Thus, the fluorine substituent in the trans-2-position
      in these examples did not change the regioselectivity but rather influenced the
      stereochemistry of biotransformation, depending on the absolute configuration of
      the substrate and ring size.

PMID- 11975563
TI  - Nickel(0)/dihydroimidazol-2-ylidene complex catalyzed coupling of aryl chlorides
      and amines.
AB  - A general and simple nickel-catalyzed coupling of aryl chlorides and amines is
      reported. The scope and limitations of the coupling process using Ni(0), 1,3
      bis(2,6-diisopropylphenyl)dihydroimidazol-2-ylidene, and NaO-t-Bu as base were
      investigated. Secondary cyclic and acyclic amines and anilines provided the
      arylamine coupling products in good to excellent yields. Compared to palladium
      catalyzed aminations, this procedure offers an alternative route to N-substituted
      anilines starting from readily available aryl chlorides.

PMID- 11975564
TI  - Synthesis of diazadibenzoperylenes and characterization of their structural,
      optical, redox, and coordination properties.
AB  - Tetraphenoxy-substituted diazadibenzoperylenes 5a,b were synthesized from
      tetrachloroperylene tetracarboxylic acid bisanhydride 1 through imidization with
      benzylamine, nucleophilic displacement of the four chlorine atoms by phenolates,
      carbonyl group reduction by LiAlH(4)/AlCl(3), and subsequent Pd/C-promoted
      debenzylation-dehydrogenation. The structural properties of these extended
      diazaarenes are discussed on the basis of a X-ray crystal structure of the N,N'
      dibutylated diazadibenzoperylenium dication 6, which revealed a 25 degrees twist
      of the central six-membered ring leading to an atropisomeric pi-conjugated
      backbone. The chromophoric systems of 5 and 6 were characterized by optical
      absorption and fluorescence spectroscopy, which revealed an intense fluorescence
      with a quantum yield of 75% for 5 and 50% for 6. Cyclic voltammetry showed
      reversible oxidation and reduction waves for 6, whereas the oxidation of 5
      afforded the irreversible deposition of a conductive film on the electrode
      surface. Finally, the potential use of ligands 5 in supramolecular chemistry has
      been evaluated by complexation experiments with carboxylic acids and zinc
      tetraphenylporphyrin (ZnTPP).

PMID- 11975565
TI  - Preparation of new microgel polymers and their application as supports in organic
      synthesis.
AB  - A series of soluble microgel polymers have been synthesized using solution-phase
      polymerization reactions. In a systematic manner, several variables such as
      monomer concentration, cross-linker content, reaction solvent and reaction time
      were examined, and this provided an optimal polymer with both solubility and
      precipitation characteristics suitable for synthetic applications. Thus, a
      chemically functionalized microgel polymer was synthesized, and the utility of
      this polymer in the synthesis of a small array of oxazole compounds has been
      demonstrated. The advantage of the microgel polymers produced was that they
      exhibited solution viscosities lower than those of conventional linear polymers
      even at higher concentrations, and this was found to be beneficial for their
      precipitation properties. Compounds prepared using the described microgel polymer
      supports were obtained in similar yields and purity when compared with insoluble
      resins, and more importantly, the soluble polymer bound intermediates could be
      analyzed at each step using standard NMR techniques.

PMID- 11975566
TI  - Carbenoid reactions of 2-halomethyl-4,6-dimethyl-s-triazines.
AB  - Reactions of lithium, sodium, and potassium salts of 2,4,6-trimethyl-s-triazine
      (1) with 2-halomethyl-4,6-dimethyl-s-triazine (2) (X = Cl, Br) in glyme have been
      studied and found to give 1,2-bis(4,6-dimethyl-s-triazin-2-yl)ethane (3), 1,2
      bis(4,6-dimethyl-s-triazin-2-yl)ethene (5), 1,2,3-tris(4,6-dimethyl-s-triazin-2
      yl)cyclopropane (6), 1,2,3-tris(4,6-dimethyl-s-triazin-2-yl)propane (7), and
      1,2,3,4-tetrakis(4,6-dimethyl-s-triazin-2-yl)butane (8). It is proposed that
      product 3 is formed primarily via an S(N)2 reaction, whereas the remaining
      products are formed primarily via carbenoid reactions that are enumerated.

PMID- 11975567
TI  - Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)
      catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides.
AB  - The cycloaddition of azides to alkynes is one of the most important synthetic
      routes to 1H-[1,2,3]-triazoles. Here a novel regiospecific copper(I)-catalyzed
      1,3-dipolar cycloaddition of terminal alkynes to azides on solid-phase is
      reported. Primary, secondary, and tertiary alkyl azides, aryl azides, and an
      azido sugar were used successfully in the copper(I)-catalyzed cycloaddition
      producing diversely 1,4-substituted [1,2,3]-triazoles in peptide backbones or
      side chains. The reaction conditions were fully compatible with solid-phase
      peptide synthesis on polar supports. The copper(I) catalysis is mild and
      efficient (>95% conversion and purity in most cases) and furthermore, the X-ray
      structure of 2-azido-2-methylpropanoic acid has been solved, to yield structural
      information on the 1,3-dipoles entering the reaction. Novel Fmoc-protected amino
      azides derived from Fmoc-amino alcohols were prepared by the Mitsunobu reaction.

PMID- 11975568
TI  - Studies toward the synthesis of alpha-fluorinated phosphonates via tin-mediated
      cleavage of alpha-fluoro-alpha-(pyrimidin-2-ylsulfonyl)alkylphosphonates.
      Intramolecular cyclization of the alpha-phosphonyl radicals.
AB  - Treatment of the alpha carbanions generated from several alpha-(pyrimidin-2
      ylsulfonyl)alkylphosphonates with Selectfluor gave high yields of the alpha
      fluoro-alpha-(pyrimidin-2-ylsulfonyl)alkylphoshonates, which were desulfonylated
      [Bu(3)SnH/2,2'-azobisisobutyronitrile (AIBN)/benzene or toluene/Delta] to give
      alpha-fluoroalkylphosphonates. "Catalytic" tin hydride, generated from
      tributyltin chloride and excess polymethylhydrosiloxane in the presence of
      potassium fluoride, also effected removal of the pi-deficient alpha-(pyrimidin-2
      ylsulfonyl) group from the phosphonate esters. Substitution of Bu(3)SnD for
      Bu(3)SnH gave access to alpha-deuterium-labeled phosphonates. Prolonged treatment
      of alpha-(pyridin-2-ylsulfonyl)alkylphosphonate with excess Bu(3)SnH/AIBN or
      catalytic tin hydride also effected desulfonylation but in moderate yields. This
      represents a mild new methodology for removal of the synthetically useful pi
      deficient heterocyclic sulfone moiety and an alternative route for the
      preparation of alpha-fluorinated phosphonates. Desulfonylation is suggested to
      proceed via attack of tin radical at an oxygen (or sulfur) atom of the sulfonyl
      group to give a stabilized alpha-phosphonyl radical intermediate. The latter was
      found to undergo 5-exo-trig ring closure to give the corresponding 2
      methylcyclopentylphosphonates. Treatment of diethyl 1-bromohex-6-enylphosphonate
      with Bu(3)SnH/AIBN produced an analogous mixture of ring-closure products.
      Treatment of [(2-bromo-5- methoxyphenyl)(fluoro)(pyrimidin-2
      ylsulfonyl)]methylphosphonate with Bu(3)SnH resulted in an intramolecular radical
      [1,5]-ipso substitution reaction and migration of the pyrimidinyl ring to give
      fluoro[5-methoxy-2-(pyrimidin-2-yl)phenyl]methylphosphonate.

PMID- 11975569
TI  - Conformational control of flexible molecules: design and synthesis of novel
      chiral 1,5-diaza-cis-decalins.
AB  - Control of the conformational equilibria of 1,5-diaza-cis-decalins, a new class
      of chiral diamine ligands, has been investigated. Chiral 2,6- and 3,7-substituted
      derivatives of 1,5-diaza-cis-decalins were designed to stabilize the
      conformational form needed to chelate a lithium. These derivatives were
      synthesized in optically pure form starting from 1,5-diaza-cis-decalin. Due to
      the rigid and conformationally well-defined nature of these compounds, the
      potential of these compounds as chiral diamine ligands was investigated.
      Asymmetric lithiation-substitution reactions of N-Boc-pyrrolidine and N,N
      diisopropyl-o-ethylbenzamide were performed using these ligands and up to 60% ee
      was obtained. For the latter substrate, results spanning a range from 32% ee (R)
      to 60% ee (S) were obtained (Delta ee = 92%) with 1,5-diaza-cis-decalin ligands
      differing only in the location of two methyl substituents. Unlike many other
      diamines that have been employed in asymmetric lithiation-substitution reactions,
      the limited conformational flexibility of the 1,5-diaza-cis-decalins is analogous
      to (-)-sparteine such that these results may permit the construction of structure
      activity relationships.

PMID- 11975570
TI  - Computational and experimental studies of the effect of substituents on the
      singlet-triplet energy gap in phenyl(carbomethoxy)carbene.
AB  - The effect of aromatic substitution on the singlet-triplet energy gap in
      substituted phenyl(carbomethoxy)carbene (X-Ph-C-CO(2)CH(3), PCC) has been
      explored by time-resolved infrared (TRIR) spectroscopy and gas-phase
      computational methods. The ground state of para-substituted PCC is calculated to
      change from the triplet state in p-NO(2)-PCC (Delta G(ST) = 6.1 kcal/mol) to the
      singlet state in p-NH(2)-PCC (Delta G(ST) = -2.8 kcal/mol). The absence of
      solvent perturbation in the TRIR spectra of p-N(CH(3))(2)-PCC (which should have
      electronic properties similar to p-NH(2)-PCC) and parent PCC is consistent with
      their ground states lying > +/-2 kcal/mol from the next available electronic
      state, in line with the computational results. The observation of solvent
      perturbation in the TRIR spectra of p-OCH(3)-PCC and p-CH(3)-PCC implies that
      their ground states lie < +/-1 kcal/mol from their next available electronic
      state. This is in agreement with our computational results, which predict a gas
      phase Delta G(ST) of -0.8 and 1.6 kcal/mol for p-OCH(3)-PCC and p-CH(3)-PCC as
      compared to Delta G(ST) values of -3.9 and -1.3 kcal/mol from polarizable
      continuum model (PCM) calculations with acetonitrile as a solvent. Gas-phase
      computational results for the meta- and ortho-substituted PCC species are also
      presented, along with selected linear free energy (LFE) relationships for the
      para and meta species.

PMID- 11975571
TI  - Conformational studies by dynamic NMR. 89. Stereomutation and cryogenic
      enantioseparation of conformational antipodes of hindered aryl oximes.
AB  - Aryl benzyl oximes having the configuration Z give rise to stereolabile
      atropisomers when a halogen atom is present in the ortho position of the aryl
      moiety, as a consequence of the restricted aryl-CN bond rotation. By means of
      dynamic (1)H NMR spectroscopy it has been possible to determine the corresponding
      rotation barrier, hence the lifetime of the atropisomers that, in the case of the
      iodine derivative, was found sufficiently long as to allow a physical separation
      to be achieved on an appropriately cooled enantioselective HPLC column.
      Comparison of the barriers determined by dynamic NMR and dynamic HPLC proved the
      equivalence of the two techniques. When the iodine atom was substituted by an
      alpha-naphthyl group, two dynamic processes were observed. That with the lower
      barrier could be determined by NMR and that with the higher barrier by HPLC, thus
      outlining the complementarity of these two techniques.

PMID- 11975573
TI  - 1,2- vs 1,4-Addition of acylbenzotriazoles to alpha,beta-unsaturated aldehydes
      and ketones. A novel route to 3-alkyl-4,6-diaryl-3,4-dihydropyran-2-ones.
AB  - Lithiation of aliphatic 1-acylbenzotriazoles with subsequent reaction with
      alpha,beta-unsaturated ketones and aldehydes affords either 3,4,6-trisubstituted
      3,4-dihydropyran-2-ones or 1,3-dienes depending on the carbonyl reagent used.
      Substituent effects on product yield and isomer ratio are discussed.

PMID- 11975572
TI  - Wittig-type olefination catalyzed by PEG-telluride.
AB  - Soluble poly(ethylene glycol) (PEG)-supported telluride 2 was designed and
      synthesized for catalytic Wittig-type reactions. It was found that the catalytic
      loading could be reduced from 20 to 2 mol % by the introduction of PEG (even to
      0.5 mol % when some telluride salts were used as the catalyst). Under the
      catalytic reaction conditions, a wide variety of aldehydes with different
      structures could react with bromoacetate to afford beta-substituted or alpha,beta
      disubstituted unsaturated esters in high yields with excellent E
      stereoselectivity. The modified process, by using sodium bisulfite instead of
      triphenyl phosphite, represented a very simple product isolation procedure. The
      roles of PEG for promoting the ylide formation and stabilizing the catalytic
      species were disclosed. The mechanism was also studied.

PMID- 11975574
TI  - Convenient syntheses of unsymmetrical imidazolidines.
AB  - Unsymmetrical imidazolidines 10-14, optically active imidazolidines 20-22, and
      2,3-dihydro-1H-benzimidazoles 28 and 29 were synthesized in good to excellent
      yields by Mannich reactions of 1,2-ethanediamines 8a-c, 18a-c, or N-methyl-1,2
      benzenediamine (26a) with benzotriazole and formaldehyde, followed by the
      nucleophilic substitution of the benzotriazolyl group with C-nucleophiles
      (Grignard reagents, sodium cyanide), an S-nucleophile (benzenethiol), and a P
      nucleophile (triethyl phosphite).

PMID- 11975575
TI  - Novel syntheses of hexahydropyrimidines and tetrahydroquinazolines.
AB  - 1-Benzotriazolylmethyl-3-propylhexahydropyrimidine (1) and 1,3-bis(1H-1,2,3
      benzotriazol-1-ylmethyl)-1,2,3,4-tetrahydroquinazoline (3) were readily prepared
      by reactions of N-propyl-1,3-propanediamine or 2-aminobenzylamine with
      benzotriazole and formaldehyde, respectively. Intermediate 1 reacted with alkyl
      and aryl Grignard reagents to produce N,N'-unsymmetrically substituted
      hexahydropyrimidines 2a,b in 90 and 92% yields, respectively. Nucleophilic
      substitutions of 3 with Grignard reagents, allylsilane, and triethyl phosphite
      gave N,N'-disubstituted 1,2,3,4-tetrahydroquinazolines 4a-f, 5, and 6 in good to
      excellent yields. Successive treatment of 3 with two different Grignard reagents
      in one-pot reaction led regiospecifically to N,N'-unsymmetrically substituted
      tetrahydroquinazoline derivatives 8a,b.

PMID- 11975577
TI  - Designed, folded polypeptide scaffolds that combine key biosensing events of
      recognition and reporting.

PMID- 11975576
TI  - A novel rearrangement to 1,2,4-triazolo[1,5-a]quinoxalines.
AB  - Reactions of benzyl bromide or benzyl cinnamate with N-(benzotriazol-1
      ylmethyl)arylimidoyl chlorides (2a,b) in the presence of t-BuOK occur with
      opening of the benzotriazole ring affording 1,2,4-triazolo[1,5-a]quinoxalines
      (3a,b). A possible reaction mechanism is discussed.

PMID- 11975578
TI  - Acid-catalyzed formation of hexahomooxacalix[3]arenes.
AB  - The role of acid catalysis in oxacalix[3]arene synthesis has been investigated. A
      range of acids were used to optimize the yield of tert-butyloxacalix[3]arene, the
      most efficient being p-toluenesulfonic acid, which, with local symmetry
      complementary with that of the lower rim of the calixarene, provides a templating
      effect.

PMID- 11975579
TI  - Synthesis of 4-acetylisocoumarin: first total syntheses of AGI-7 and sescandelin.
AB  - A practical synthetic route to 4-acetylisocoumarins and the first total synthesis
      of AGI-7 (5) and sescandelin (4) are described. The readily available
      homophthalate 8 was transformed to the vinylogous amide ester 13 in high overall
      yield. Upon treatment of 13 with refluxing aqueous formic acid, the desired 4
      acetylisocoumarin (5) and its regioisomer 3-methyl-4-formylisocoumarin (17) were
      produced in a 3:1 ratio. After separation of the desired product (5) from the
      unwanted minor isomer, the enantioselective reduction of AGI-7 by borane in the
      presence of Corey's (S)-oxazaborolidine reagent afforded (+)-sescandelin (4) with
      a 93% ee.

PMID- 11975580
TI  - Practical asymmetric synthesis of the herbicide (S)-indanofan via lipase
      catalyzed kinetic resolution of a diol and stereoselective acid-catalyzed
      hydrolysis of a chiral epoxide.
AB  - Racemic indanofan [(+/-)-1] was efficiently converted to enantiopure (S)
      indanofan [(S)-1] by a combination of enzymatic resolution and chemical inversion
      techniques. An additional important technique is the use of an o-xylene complex
      of a hemiketal (S)-3c as a precursor, which can be quantitatively converted to
      (S)-indanofan and easily purified by recrystallization from o-xylene.

PMID- 11975581
TI  - A preliminary approach to nonenolizable beta,beta-tricarbonyls: assembly of a
      hyperevolutin prototype.
AB  - A synthetic approach to the hyperevolutin A acylated phloroglucinol ring system
      is described. Thus, intramolecular allene-nitrile oxide cycloaddition of 10 was
      used to construct the bicyclic framework and vicinal quaternary centers in
      cycloadduct 20 in the key bond-forming step. Treatment of 20 with Raney nickel
      and hydrogen gas produced primary enamine 21 which contains a nonenolizable
      beta,beta-tricarbonyl group in latent form.

PMID- 11975582
TI  - Solid-phase synthesis of 1,5-disubstituted 2-aryliminoimidazolidines.
AB  - The solid-phase synthesis of 1,5-disubstituted 2-aryliminoimidazolidines,
      starting from resin-bound N-acylated amino acid amides, is described. Exhaustive
      reduction of resin-bound acylated amino acid amides with borane-THF afforded the
      corresponding disecondary amines. Further reaction with arylisothiocyanates in
      the presence of mercuric chloride (HgCl(2)) yielded the corresponding resin-bound
      1,5-disubstituted 2-aryliminoimidazolidines. Cleavage of the product from the
      resin using HF/anisole (95/5) for 1.5 h at 0 degrees C gave the desired products
      in good yield and purity. The preparation of a large combinatorial library of
      such compounds is also discussed.

PMID- 11975583
TI  - An improved synthesis of cyclopropanes from stabilized phosphonates and 1,2
      dioxines.
AB  - Addition of stabilized Horner-Wadsworth-Emmons (HWE) phosphonates to substituted
      1,2-dioxines leads to diastereomerically pure di- and trisubstituted
      cyclopropanes in high yields and represents a viable alternative to ylides in the
      cyclopropanation reaction involving 1,2-dioxines. While yields are comparable,
      reaction times with these stabilized phosphonates were accelerated and the
      diastereoselectivity for this cyclopropanation reaction was significantly greater
      than for the previously reported examples employing ylides.

PMID- 11975584
TI  - A study of the ionic liquid mediated microwave heating of organic solvents.
AB  - The use of ionic liquids as aids for microwave heating of nonpolar solvents has
      been investigated. We show that hexane and toluene together with solvents such as
      THF and dioxane can be heated way above their boiling point in sealed vessels
      using a small quantity of an ionic liquid, thereby allowing them to be used as
      media for microwave-assisted chemistry. Using the appropriate ionic liquid, the
      heating can be performed with no contamination of the solvent. To show the
      applicability of the system, two test reactions have been successfully performed.

PMID- 11975585
TI  - Trimethylsilylethynyl ketones as surrogates for ethynyl ketones in the double
      Michael reaction.
AB  - Trimethylsilylethynyl ketones can be desilylated in the presence of a tethered
      carbon diacid and induced to undergo a double Michael reaction in situ. The
      trimethylsilylethynyl ketones can serve as surrogates of ethynyl ketones that are
      difficult to prepare or isolate.

PMID- 11975586
TI  - Application of ruthenium-induced macrocyclization for the construction of
      macrocyclic depsipeptides.
AB  - The synthesis of a biaryl ether containing macrocyclic depsipeptide 1 was
      achieved in 6% overall yield. The desired macrocycle was constructed by
      cyclization of a phenol into eta(6)-ruthenium complex. The ruthenium metal was
      subsequently photolytically deprotected to obtain the macrocycle 1.

PMID- 11975587
TI  - Convenient synthesis of 3,3,3-trifluoropropenyl compounds from aromatic aldehydes
      by means of the TBAF-mediated Horner reaction.
AB  - A simple synthesis of 3,3,3-trifluoropropenyl compounds by means of the TBAF
      mediated Horner reaction is described. The reagent, 2,2,2
      trifluoroethyldiphenylphosphine oxide, was readily prepared either by Arbuzov
      reaction of ethyl diphenylphosphinite with 2,2,2-trifluoroethyl iodide or by
      treating chlorodiphenylphosphine with trifluoroacetic acid and water. Treatment
      of the phosphine oxide with aromatic aldehydes in the presence of TBAF at room
      temperature afforded the corresponding 3,3,3-trifluoropropenyl compounds in good
      yields. The present method is very convenient for preparing 3,3,3
      trifluoropropenyl compounds from aromatic aldehydes in terms of availability of
      the reagent, operational simplicity, and good yields of the products.

PMID- 11975588
TI  - Facile synthesis of novel functionalized bis(ethylenedithio)tetrathiafulvalene
      (BEDT-TTF) derivatives.
AB  - An improved and efficient synthetic route to four functionalized
      bis(ethylenedithio)-tetrathiafulvalene (BEDT-TTF) derivatives 2-5 is reported.
      Tetrathiolate 1 was readily prepared from 2,2'-bis(1,3,4,6-tetrathiapentalen-5
      one) under carefully controlled conditions. Subsequent reaction of 1 with
      selected primary alkyl halides affords new functionalized BEDT-TTF derivatives in
      good yields.

PMID- 11975589
TI  - Wilkinson's catalyst catalyzed selective hydrogenation of olefin in the presence
      of an aromatic nitro function: a remarkable solvent effect.
AB  - Optimal conditions for chlorotris(triphenylphosphine)rhodium(I) (Wilkinson's
      catalyst) catalyzed selective saturation of a double bond in the presence of a
      nitro function are developed. Aryl iodide and benzyl ether are also tolerated
      under these hydrogenation conditions.

PMID- 11975590
TI  - Syntheses and conformations of tetrahomodioxacalix[4]arene tetraamides and
      tetrathioamides.
AB  - A series of tetrahomodioxacalix[4]arene tetraamides and tetrathioamides with four
      p-phenyl groups on their upper rim were synthesized. From the (1)H and (13)C NMR
      and crystal structure, N-butylamido homooxacalix[4]arene (4) was found to be in
      the 1,3-alternate conformation and has intramolecular hydrogen bonding between N
      H and facing oxygen atoms of the carbonyl O=C group. This hydrogen bonding
      decreased the metal ion complex ability. Transformation of the 1,3-alternate N
      butylamido (4) into N-butylthioamido homooxacalix[4]arene (5) using Lawesson's
      reagent gave a conformational change to the C-1,2-alternate.

PMID- 11975591
TI  - Carbamoyl-substituted N-heterocyclic carbene complexes of palladium(II):
      application to Sonogashira cross-coupling reactions.
AB  - [reaction: see text]. The first examples of N-carbamoyl-substituted heterocyclic
      carbene Pd(II) complexes are described. These thermal and hydrolytically stable
      complexes are readily prepared from carbamoyl imidazolium salts and efficiently
      promote Sonogashira cross-coupling reactions under mild conditions. Cesium
      carbonate is also shown to be an effective base for the coupling of aryl
      bromides.

PMID- 11975592
TI  - Modular evolution of a chiral auxiliary for the 1,3-dipolar cycloaddition of
      isomunchnones with vinyl ethers.
AB  - [reaction: see text]. The 1,3-dipolar cycloaddition reaction has long been
      recognized as a powerful methodology in organic synthesis. More recently, this
      reaction has become a popular manifold for the construction of chemical
      diversity. Herein, we report the development of a chiral template for the
      facially selective cycloaddition of isomunchnones, a common class of 1,3-dipoles.
      The modular format of the asymmetric unit allowed a systematic optimization of
      selectivity. In addition, the chiral auxiliary was removed through an unusually
      facile ester aminolysis.

PMID- 11975593
TI  - Diastereofacial solid phase synthesis and self-promoted cleavage of a [2.2.1]
      bicyclic diversity scaffold.
AB  - [reaction: see text]. We have previously described a diastereofacially selective
      1,3-dipolar cycloaddition reaction of isomunchnones with vinyl ethers. While
      adapting this methodology for solid phase synthesis, we discovered a
      chemoselective and self-promoted linker aminolysis that provides liberated
      product in high purity, at a significantly enhanced rate. Herein we describe the
      implementation of a chiral auxiliary as a solid-phase linker, the detailed
      investigation of its unique aminolysis, and the utility of this cleavage within a
      chemical diversity format.

PMID- 11975594
TI  - Molecular design of "super" hydrogelators: understanding the gelation process of
      azobenzene-based sugar derivatives in water.
AB  - [structure: see text]. 1: R = beta-D-glucopyranoside. 2: R = alpha-D
      glucopyranoside. 3: R = alpha-D-galactopyranoside. 4: R = alpha-D
      mannopyranoside. As an attempt to rationally design aqueous organogelators, a
      bolaamphiphilic azobenzene derivative (1) bearing two sugar groups was
      synthesized. Compound 1 formed a gel in water even at concentrations as low as
      0.05 wt % (0.65 mM). Spectroscopic studies and electron-micrographic observations
      have clarified the gel structure and the origin of the gelation ability for
      water.

PMID- 11975595
TI  - Synthesis of an influenza neuraminidase inhibitor intermediate via a highly
      diastereoselective coupling reaction.
AB  - [reaction: see text]. A highly diastereoselective coupling reaction between TBSOP
      (3) and trityl sulfenimine 4 was developed which provided influenza neuraminidase
      inhibitor intermediate 7 in 80% yield and >99% de after crystallization. The
      reaction was shown to be reversible with the high diastereoselectivity resulting
      from a favorable H-bonding interaction in the major diastereomer.

PMID- 11975596
TI  - Integramides A and B, two novel non-ribosomal linear peptides containing nine
      C(alpha)-methyl amino acids produced by fungal fermentations that are inhibitors
      of HIV-1 integrase.
AB  - [structure: see text]. Integramides A and B are two novel 16-mer linear peptides
      rich in C(alpha)-methyl amino acids that were isolated from fungal extracts of
      Dendrodochium sp. by employing a bioassay-guided isolation procedure using
      recombinant HIV-1 integrase. The structure and stereochemistry were elucidated by
      a combination of 2D NMR and ESI- and FAB-MS including MS/MS studies and by
      Marfey's method. Integramides A and B inhibited the coupled reaction of HIV-1
      integrase with IC50 values of 17 and 10 microM, respectively.

PMID- 11975597
TI  - Formation of a novel arenium ion from the radical cation of a twisted
      triphenylene fully annelated with bicyclo[2.2.2]octene units.
AB  - [reaction: see text]. Triphenylene 1 was synthesized by palladium-catalyzed
      cyclotrimerization of a benzyne annelated with two bicyclo[2.2.2]octene (BCO)
      units. Theoretical calculations indicated that 1 is constrained to a twisted
      conformation with a C2 symmetry as a result of steric repulsion between the BCO
      units. The one-electron oxidation of 1 with SbCl5 gave the corresponding radical
      cation 1*+, which abstracted a chlorine atom in the medium with the concomitant
      rearrangement to form novel arenium ion 2+.

PMID- 11975598
TI  - Preparation of alpha-C-glycosides from glycals.
AB  - [reaction: see text]. A novel approach to simple C-glycosides is reported.
      Reductive ring opening of 1,2-anhydro sugars with titanocene(III) chloride
      produces an anomeric radical that can be trapped with a variety of agents. The
      reaction stereospecifically affords alpha-glycosides and produces a free C-2
      hydroxyl group allowing for further elaboration.

PMID- 11975599
TI  - Control of enantioselectivity in the photochemical conversion of alpha-oxoamides
      into beta-lactam derivatives.
AB  - [reaction: see text]. Several approaches to asymmetric induction in the alpha
      oxoamide (1) to beta-lactam (2) photorearrangement are described. Best results
      are obtained via irradiation of ionic and covalent chiral auxiliary-containing
      reactants in the crystalline state and in the interior supercages of zeolites.

PMID- 11975600
TI  - Studies on the biosynthesis of phomoidride B (CP-263,114): evidence for a
      decarboxylative homodimerization pathway.
AB  - [reaction: see text]. Feeding experiments using a deuterium labeled C16 maleic
      anhydride and whole cell culture of ATCC 74256 led to the isolation of
      phomoidride B with deuterium incorporation at C(7) and C(19) as determined by 2H
      NMR and electrospray mass spectrometry. This result is in accord with a
      decarboxylative homodimerization of the C16 maleic anhydride as a key
      biosynthetic step leading to phomoidride B.

PMID- 11975601
TI  - Progress toward a biomimetic synthesis of phomoidride B.
AB  - [reaction: see text]. An intramolecular cyclization strategy for effecting a
      biomimetic synthesis of the core structure of the fungal secondary metabolites
      phomoidrides A and B is described. The cyclization substrate 20 is prepared in
      eight steps from dibromide 10. Treatment of 20 with triethylamine in acetonitrile
      results in a rapid cyclization to give 21 and 22 in good yield.

PMID- 11975602
TI  - Chiral biscavitand propellers: synthesis, conformations and multiple guest
      binding.
AB  - [structure: see text]. The synthesis and properties of molecules containing two
      cavitand bowls, with interbowl linkages comprising one carbon atom at various
      oxidation levels, are reported. A carbonyl-bridged biscavitand binds three CH2Cl2
      molecules in the solid state through a helical conformation. Evidence for the
      same chiral conformation in the solution phase is presented.

PMID- 11975603
TI  - Alkylation of nucleic acids by the antitumor agent COMC.
AB  - [reaction: see text]. Mass spectral data are presented indicating that the
      antitumor agent 2-crotonyloxymethyl-2-cyclohexenone (COMC) is capable of
      alkylating oligonucleotides via a mechanism involving an electrophilic exocyclic
      enone intermediate. Under physiological conditions, the exocyclic enone is likely
      the glutathionylated 2-exomethylenecyclohexenone. This supports a recent
      hypothesis that the antitumor activity of COMC arises from alkylation of nucleic
      acids and/or proteins critical to cell function and not from competitive
      inhibition of glyoxalase I by an adduct of COMC and glutathione.

PMID- 11975604
TI  - Dialkylzinc-assisted alkynylation of nitrones.
AB  - [reaction: see text]. Reaction of nitrones with terminal alkynes takes place
      readily in the presence of a substoichiometric amount of diethylzinc in toluene,
      affording N-propargyl-hydroxylamines in excellent yields and purity.

PMID- 11975605
TI  - Solid-phase synthesis of thioether-linked glycopeptide mimics for application to
      glycoprotein semisynthesis.
AB  - [reaction: see text]. Glycoproteins are particularly suited to protein
      semisynthesis since homogeneous samples for biological analyses are not readily
      available using traditional recombinant techniques. Here we apply glycosyl
      iodoacetamides, normally used for the modification of bacterially derived
      proteins, to solid-phase glycopeptide synthesis. This provides access to
      glycopeptide alpha-thioesters, which may lend themselves to the semisynthesis of
      homogeneous N-linked glycoprotein mimics and novel glycopeptide libraries.

PMID- 11975606
TI  - Bronsted acid-catalyzed intramolecular hydroamination of protected alkenylamines.
      Synthesis of pyrrolidines and piperidines.
AB  - [reaction: see text]. The cyclization of aminoalkenes bearing an electron
      withdrawing group on the nitrogen atom was catalyzed by triflic or sulfuric acid
      in toluene. Pyrrolidines and piperidines were formed in excellent yields. N
      phenylanilides also underwent cyclization to form gamma-lactams.

PMID- 11975607
TI  - A highly reactive titanium precatalyst for intramolecular hydroamination
      reactions.
AB  - [reaction: see text]. Tetrakisamido titanium complexes are significantly more
      active than Cp2TiMe2 (1) in the intramolecular hydroamination of aminoalkynes and
      aminoallenes. In the latter case, the regioselectivity of the transformation
      depends on the nature of the precatalyst, yielding the most selective and
      reactive catalysis with the bis(sulfonamido) complex 11.

PMID- 11975608
TI  - Facile Pd-catalyzed cross-coupling of 2'-deoxyguanosine O6-arylsulfonates with
      arylboronic acids.
AB  - [reaction: see text]. The O6-(2-mesitylenesulfonyl) derivative of 2'
      deoxyguanosine undergoes a facile palladium-mediated C-C cross-coupling with
      arylboronic acids. Demonstrating the general applicability of this method, the
      synthesis of a previously undescribed class of 2-amino-6-arylpurine 2'
      deoxynucleosides has been accomplished. The study also describes an evaluation of
      the O6-(2,4,6-triisopropylphenylsulfonyl) and the O6-(4-toluenesulfonyl)
      derivatives for the cross-coupling.

PMID- 11975609
TI  - Stereoselective preparation of (E)-(1,2-difluoro-1,2-ethenediyl)
      bis[tributylstannane] and stereospecific synthesis of (E)-1,2-difluorostilbenes.
AB  - [reaction: see text]. The novel bisstannane (E)-(1,2-difluoro-1,2-ethenediyl)
      bis[tributylstannane] 2 was stereoselectively prepared in a high overall yield
      through a sequential synthetic route from chlorotrifluoroethylene 1. The
      synthetic application of this novel bisstannane 2 was exemplified in the
      Pd(PPh3)4/CuI-catalyzed cross-coupling reactions with aryl iodides, yielding (E)
      1,2-difluorostilbenes 3 in moderate to high yields.

PMID- 11975611
TI  - A new reaction of aryl aldehydes with aryl acetylenes in the presence of boron
      trihalides.
AB  - [reaction: see text]. The reactions of aryl aldehydes with 2 equiv of
      arylacetylenes in the presence of boron trichloride yield (E,Z)-1,3,5-triaryl-1,5
      dichloro-1,4-pentadienes. Reactions carried out in the presence of boron
      tribromide generate the corresponding (Z,Z)-1,3,5-triaryl-1,5-dibromo-1,4
      pentadienes.

PMID- 11975610
TI  - Photochemistry of benzotriazole: an unprecedented tautomer-selective
      intermolecular [2+2] photocycloaddition.
AB  - [reaction: see text]. Irradiation of benzotriazole with a variety of maleimide
      derivatives leads to the stereo- and regioselective formation of aryl [2 + 2]
      photocycloaddition products. Further studies with 2-alkyl benzotriazole
      derivatives indicates that in the case of the parent benzotriazole this
      cycloaddition proceeds selectively via the 2H-tautomer.

PMID- 11975612
TI  - Novel heterocycle-based two-photon absorbing dyes.
AB  - [structure: see text]. The synthesis and nonlinear optical characterization of
      two novel heteroaromatic-based chromophores is described. The new dyes present an
      A-pi-D-pi-A general framework, where A is a pi-deficient heteroaromatic ring
      (pyridine, quinoline, benzothiazole) and D a pi-excessive pyrrolyl moiety. Both
      systems exhibit large two-photon absorption (TPA) values in the femtoseconds
      regime (TPA cross section as high as 150 x 10(-50) cm(4) s photon(-1) molecule(
      1) with 150 fs laser pulses). Their TPA-based optical limiting activity is also
      shown.

PMID- 11975613
TI  - Zirconium-mediated intramolecular ester transfer reaction: synthesis of alpha
      substituted gamma-aminobutyric acid (GABA) derivatives.
AB  - [reaction: see text]. The zirconium-mediated intramolecular ester transfer
      reaction of N-alkenyl carbamate derivatives proceeded to give alpha-substituted
      gamma-aminobutyric acid (GABA) derivatives in good to excellent yields. Quenching
      experiments of the reaction mixture with iodine or O2 indicated the presence of a
      cyclopropane intermediate. The resulting iodide was converted to 2-substituted
      pyrrolidine-3-carboxylate and/or alpha-alkylidene-gamma-aminobutyric acid
      derivatives in a stereospecific manner.

PMID- 11975615
TI  - TEMPO-catalyzed aerobic oxidation of alcohols to aldehydes and ketones in ionic
      liquid [bmim][PF6].
AB  - [reaction: see text]. A simple and mild TEMPO-CuCl catalyzed aerobic oxidation of
      primary and secondary alcohols to the corresponding aldehydes and ketones in
      ionic liquid [bmim][PF6] with no trace of overoxidation to carboxylic acids has
      been developed. The product can be isolated by a simple extraction with organic
      solvent, and the ionic liquid can be recycled or reused.

PMID- 11975614
TI  - Monoboronic acid sensor that displays anomalous fluorescence sensitivity to
      glucose.
AB  - [reaction: see text]. A monoboronic acid fluorescent sensor was conveniently
      synthesized from 3-nitronaphthalic anhydride and 3-aminophenylboronic acid. This
      novel saccharide probe exhibits dual emission suitable for ratiometric sensing
      and displays a remarkable sensitivity for glucose relative to fructose and
      galactose.

PMID- 11975616
TI  - Tandem base-promoted ring opening/brook rearrangement/allylic alkylation of O
      silyl cyanohydrins of beta-silyl-alpha,beta-epoxyaldehydes.
AB  - [reaction: see text]. Metalated O-silyl cyanohydrins of beta-silyl-alpha,beta
      epoxyaldehyde have been found to serve as functionalized homoenolate equivalents
      by a tandem sequence involving a base-promoted ring opening of the epoxide, Brook
      rearrangement, and alkylation of the resulting allylic anion.

PMID- 11975617
TI  - Total synthesis of (+/-)-stenine using the IMDAF cycloaddition of a 2-methylthio
      5-amido-substituted furan.
AB  - [reaction: see text]. The intramolecular [4 + 2]-cycloaddition of a 2-methylthio
      5-amidofuran was used to create the azepinoindole skeleton present in the Stemona
      alkaloid stenine. The rearranged cycloadduct was converted to stenine (1) in 11
      additional steps via a sequence that features a Crabtree catalyst directed
      hydrogenation (9-->10), iodolactonization (2-->11), and a Keck allylation (11-
      >12).

PMID- 11975618
TI  - Microencapsulated VO(acac)2: preparation and use in allylic alcohol epoxidation.
AB  - [reaction: see text]. Microencapsulated VO(acac)2 [MC-VO(acac)2] has been
      prepared and screened with success as a catalyst for the epoxidation of allylic
      alcohols using tert-butyl hydroperoxide as oxidant. The reactions are run in
      hexane at room temperature. The MC-VO(acac)2 is reusable without significant loss
      of activity.

PMID- 11975619
TI  - Synthesis and spectroscopic studies of model red fluorescent protein
      chromophores.
AB  - [reaction: see text]. Here we describe the synthesis and spectroscopic
      characterization of two compounds designed to model the chromophore in DsRed, a
      red fluorescent protein. Comparison with model green fluorescent protein (GFP)
      chromophores indicates that the additional conjugation in the DsRed models can
      account, in part, for the red-shifted absorption and emission properties of DsRed
      compared to those of GFP. In contrast to the GFP models, the DsRed models are
      fluorescent with quantum yields of 0.002-0.01 in CHCl3.

PMID- 11975620
TI  - Short synthesis of the CDEF ring system of lactonamycin.
AB  - [reaction: see text]. A synthesis of the CDEF fragment of lactonamycin is
      achieved in eight steps (six pots) from the known and readily available anhydride
      4 via a Diels-Alder reaction between tricycle 13 and 2,3-dimethylbenzoquinone.

PMID- 11975621
TI  - Regioselective O-substitution of p-tert-butylcalix[7]arene.
AB  - [structure: see text]. The first examples of selectively functionalized
      calix[7]arenes have been obtained by weak-base promoted O-alkylation or O
      benzoylation of p-tert-butylcalix[7]arene. Mono-, 1,3- and 1,4-disubstituted
      calix[7]arenes have been obtained in workable yields, while the 1,2,4,6
      tetrasubstitution was achieved with surprisingly high selectivity (50-88% yield)
      by using K2CO3 as base. A rationale for this finding is proposed.

PMID- 11975622
TI  - Caylobolide A, a unique 36-membered macrolactone from a Bahamian Lyngbya
      majuscula.
AB  - [structure: see text]. A new 36-membered macrolactone, (25S,27S,29S,33S)
      caylobolide A, was isolated from the Bahamian cyanobacterium Lyngbya majuscula.
      The structure of caylobolide contains an unprecedented repeated unit-a contiguous
      pentad of 1,5 diols-and a 1,3,5-triol. The relative steroechemistry of the 1,3,5
      triol was determined using Kishi's Universal NMR database, and absolute
      stereochemistry at C25,27,29 and C33 were determined by Mosher's analysis.
      Caylobolide A exhibited in vitro cytotoxicity against human colon tumor cells
      (IC50 HCT 116, 9.9 microM).

PMID- 11975623
TI  - Partial stereochemical assignment of quartromicins A3 and D3.
AB  - [structure: see text]. A partial stereochemical assignment of quartromicins A3 (R
      = alpha-D-galactosyl) and D3 (R = H, M+ = Na+, K+, Ca+) is presented.

PMID- 11975624
TI  - Diastereoselective synthesis of the endo- and exo-spirotetronate subunits of the
      quartromicins. The first enantioselective Diels-Alder reaction of an acyclic (Z)
      1,3-diene.
AB  - [reaction: see text]. Diastereoselective syntheses of the endo- and exo
      spirotetronates 1 and 2, corresponding to the galacto and agalacto fragments of
      quartromicins A3 and D3, are described. The key step of these syntheses are
      highly enantio- and diastereoselective Lewis acid catalyzed Diels-Alder reactions
      of the 1,1,3,4-tetrasubstituted diene 3.

PMID- 11975626
TI  - Stereospecific beta-lithiation of oxazolinyloxiranes: synthesis of alpha,beta
      epoxy-gamma-butyrolactones.
AB  - [reaction: see text]. Stereospecific beta-lithiation of beta-aryl-substituted
      oxazolinyloxiranes is described. The trapping reaction of such reactive
      intermediates with carbonyl compounds gave alpha,beta-epoxy-gamma-butyrolactones
      after deblocking of the oxazoline moiety. This methodology has been also extended
      to the synthesis of optically active alpha,beta-epoxy-gamma-butyrolactones.

PMID- 11975625
TI  - Silyl-substituted amino acids: new routes to the construction of selectively
      functionalized peptidomimetics.
AB  - [reaction: see text]. Silylated amino acids have been incorporated into peptides
      and then converted into N-acyliminium ions with the use of an anodic oxidation
      reaction. The result is a method for selectively incorporating conformational
      constraints or external nucleophiles within the peptide.

PMID- 11975627
TI  - Rigid tetranitroresorcinarenes.
AB  - [reaction: see text]. o-alkylation of C2V-symmetrical resorcinarene tetraesters 2
      with 2 equiv of 1,3-difluoro-4,6-dinitrobenzene readily affords conformationally
      rigid octanitro resorcinarene 3, which is a potential scaffold for the design of
      supramolecular structures.

PMID- 11975628
TI  - Dipolar recoupling in NOESY-type 1H-1H NMR experiments under HRMAS conditions.
AB  - [structure: see text]. The concept of dipolar recoupling is introduced to 1H-1H
      NOESY experiments performed under HRMAS conditions. Dipole-dipole couplings are
      selectively recoupled during the mixing period, while MAS ensures high resolution
      in the spectral dimensions. Incoherent dipolar exchange is replaced by amplified
      coherent processes, such that time scales for polarization transfer are
      shortened, and dipolar double-quantum techniques become applicable. In this way,
      dipole-dipole couplings, as well as J-couplings, can be individually measured.

PMID- 11975629
TI  - Regioselective palladium-catalyzed electrophilic allylic substitution in the
      presence of hexamethylditin.
AB  - [reaction: see text]. Palladium-catalyzed electrophilic allylic substitution of
      functionalized allyl chlorides and allyl acetates can be achieved in the presence
      of hexamethylditin under mild reaction conditions. The substitution reaction
      occurs with very high regioselectivity at the branched allylic terminus.
      Regioselective tandem bisallylation reaction could be performed by employing
      benzylidenemalonitrile as substrate. The reaction mechanism can be explained by
      involvement of a bisallylpalladium intermediate. A particularly interesting
      mechanistic feature of this reaction is that palladium catalyzes up to three
      different transformations in the same catalytic cycle. DFT calculations indicate
      that the regioselectivity is determined by the location of the allylic
      substituent in the eta1-allyl moiety of the reaction intermediate.

PMID- 11975630
TI  - Microwave-accelerated ruthenium-catalyzed olefin metathesis.
AB  - [reaction: see text]. Microwave heating is an efficient method for the
      acceleration of ring-closing metathesis reactions using ruthenium-based
      catalysts. The reaction can be rapidly conducted in either ionic liquids, such as
      1-butyl-3-methylimidazolium tetrafluoroborate (bmim), or in a microwave
      transparent solvent (MTS) such as dichloromethane.

PMID- 11975631
TI  - Synthesis of optically active trifluoromethylated indolizidine derivatives via
      stereoselective radical cyclization.
AB  - [reaction: see text]. Asymmetric Michael reaction of lithiated trifluoroacetone
      SAMP-hydrazone with alkylidenemalonates gave addition products stereoselectively.
      Hydrolyzed enantiomerically pure ketoacids were cyclized to dihydropyridinones. N
      Iodopropylation followed by radical cyclization gave optically active
      trifluoromethylated indolizidinones stereoselectively.

PMID- 11975632
TI  - A CAN-induced cyclodimerization-Ritter trapping strategy for the one-pot
      synthesis of 1-amino-4-aryltetralins from styrenes.
AB  - [reaction: see text]. A facile one-pot synthesis of 1-amino-4-aryl-tetralin
      derivatives by the CAN-induced cyclodimerization of various styrenes in
      acetonitrile and acrylonitrile is described.

PMID- 11975633
TI  - A novel short convergent entry into himbacine derivatives.
AB  - [reaction: see text]. The IMDA reaction of 9 leads with good stereoselectivity to
      exo-adduct 10b. The functionalized ABC-ring core in 10 is well suited for the
      convergent synthesis of analogues of himbacine, a naturally occurring M2
      selective muscarine receptor antagonist, as illustrated with the further
      synthesis of the dehydro-derivative 5.

PMID- 11975635
TI  - On the reactivity of o-lithioaryl ethers: tandem anion translocation and Wittig
      rearrangement.
AB  - [reaction: see text]. Allyl and benzyl 2-lithioaryl ethers, generated by bromine
      lithium exchange in THF, undergo a new tandem anion translocation-[1,2]-Wittig
      rearrangement allowing the isolation of the corresponding benzylic alcohols.

PMID- 11975634
TI  - Aspergilloxide, a novel sesterterpene epoxide from a marine-derived fungus of the
      genus Aspergillus.
AB  - [structure: see text]. A new sesterterpene epoxide-diol, aspergilloxide (1), was
      isolated from the extract of a cultured marine-derived fungus (strain CNM-713)
      identified as an undescribed member of the genus Aspergillus. The structure of 1
      was determined by interpretation of NMR data and by chemical methods. The
      absolute stereochemistry of aspergilloxide was assigned by application of the
      modified Mosher method. The carbon skeleton of 1 represents a new addition to the
      architectural diversity of the sesterterpenoid (C25) class of secondary
      metabolites.

PMID- 11975636
TI  - Palladium-catalyzed arylation of ketone enolates: an expeditious entry to
      tamoxifen-related 1,2,2-triarylethanones.
AB  - [reaction: see text]. After a rigorous study on the effect of several catalytic
      systems, a simple, high yielding procedure for the preparation of 1,2,2
      triarylethanones, skeletal analogues of tamoxifen, is presented. Apart from the
      economic and environmental advantages involved, this palladium-catalyzed
      arylation of deoxybenzoin enolates features a lack of ortho-arylation side
      reactions. In addition, an alternative approach from acetophenones to the target
      triarylethanone system is also announced.

PMID- 11975637
TI  - Application of Rh(I)-catalyzed C-H bond activation to the ring opening of 2
      cycloalkenones in the presence of amines.
AB  - [reaction: see text]. Herein described is the application of the Rh(I)-catalyzed
      C-H bond activation to the ring-opening of 2-cycloalkenones in the presence of
      cyclohexylamine. This reaction includes the C-C double bond cleavage of 2
      cycloalkenones through the conjugate addition of cyclohexylamine followed by the
      retro-Mannich-type fragmentation. The resulting ring-opened intermediates
      subsequently underwent either chelation-assisted hydroacylation to afford a ring
      opened dicarbonyl compound or beta-alkylation via a ring contraction.

PMID- 11975638
TI  - Asymmetric synthesis of substituted prolines from delta-amino beta-ketoesters.
      Methyl (2S,5R)-(+)-5-phenylpyrrolidine-2-carboxylate.
AB  - [reaction: see text]. Metal carbenoid chemistry is used to convert delta-amino
      beta-ketoesters into 5-substituted 3-oxo prolines, which expands the utility of
      this class of polyfunctionalized chiral building blocks.

PMID- 11975639
TI  - Bifunctional asymmetric catalysis: a tandem nucleophile/Lewis acid promoted
      synthesis of beta-lactams.
AB  - [reaction: see text]. We describe a superior procedure for the catalytic,
      asymmetric synthesis of beta-lactams using a bifunctional catalyst system
      consisting of a chiral nucleophile and an achiral Lewis acid.

PMID- 11975640
TI  - Ligand-assisted rate acceleration in transacylation by a yttrium-salen complex.
      Demonstration of a conceptually new strategy for metal-catalyzed kinetic
      resolution of alcohols.
AB  - [reaction: see text]. Yttrium-salen complexes effect transacylation between
      enolesters and chiral secondary alcohols, resulting in varying degrees of kinetic
      resolution. Even though the enantioselectivity remains modest (k(fast)/k(slow) up
      to 4.81), these results represent the first demonstration of a conceptually new
      metal-catalyzed acyl transfer process that results in kinetic resolution. On the
      basis of the solid-state structure of the catalyst, a novel associative
      mechanistic pathway is proposed for the reaction.

PMID- 11975642
TI  - A novel class of nonbiaryl atropisomeric P,O-ligands for palladium-catalyzed
      asymmetric allylic alkylation.
AB  - [structure: see text]. A novel class of nonbiaryl atropisomeric P,O-ligands
      possessing an N,N-dialkyl-1-naphthamide skeleton has been synthesized via an
      efficient chemical resolution process. It represents the first example of axially
      chiral P,O-ligands devoid of central chirality. Up to 94.7% ee was obtained for
      the Pd-catalyzed asymmetric allylic alkylation (AAA). Effects of solvent, base,
      and the bulk of the C8 oxygen group of the P,O-ligand on the AAA reaction were
      examined.

PMID- 11975641
TI  - Total synthesis of the putative structure of the lupin alkaloid plumerinine.
AB  - [reaction: see text]. A stereocontrolled synthesis of quinolizidine 1, the
      reported structure of plumerinine, has been accomplished in 10 steps from 4
      methoxypyridine. The key step is a highly facial selective intramolecular [2 + 2]
      photocycloaddition of a 2,3-dihydro-4-pyridone. The reported spectral data for
      plumerinine did not match that of our synthetic 1.

PMID- 11975643
TI  - Catalytic Pauson-Khand-type reaction using aldehydes as a CO source.
AB  - [reaction: see text]. Rhodium complex-catalyzed carbonylative alkene-alkyne
      coupling proceeds using aldehydes as a CO source. Cinnamaldehyde is the best CO
      donor, and various cyclopentenones were provided in high isolated yields by a
      solvent-free system.

PMID- 11975644
TI  - Ullmann diaryl ether synthesis: rate acceleration by 2,2,6,6-tetramethylheptane
      3,5-dione.
AB  - [reaction: see text]. In the copper salt catalyzed ether formation from aryl
      bromides or iodides and phenols, 2,2,6,6-tetramethylheptane-3,5-dione (TMHD) was
      found to greatly accelerate the ordinarily difficult reaction, making it occur
      under more moderate temperatures and reaction times. A series of aryl halides and
      phenols were shown to form ethers in NMP as the solvent, cesium carbonate as the
      base, and CuCl and TMHD as the catalysts. The reaction was shown to tolerate
      electron-rich aryl bromides and electron-neutral phenols.

PMID- 11975645
TI  - Construction of the benzylic quaternary carbon center of zoanthenol by
      intramolecular Mizoroki-Heck reaction of enone.
AB  - [reaction: see text]. Stereocontrolled synthesis of the ABC ring framework of
      zoanthenol has been achieved. Our studies show that a beta,beta-disubstituted
      enone can act as a good acceptor of arylpalladium intermediates in the formation
      of a congested benzylic quaternary carbon center through an intramoleculer
      Mizoroki-Heck reaction. The cis B/C ring system was stereoselectively converted
      to the trans-fused framework through a SmI2-promoted deoxygenation of the alpha
      hydroxy ketone.

PMID- 11975646
TI  - Metal-promoted variants of the Passerini reaction leading to functionalized
      heterocycles.
AB  - [reaction: see text]. The effect of replacing the Bronsted acid in classic
      Passerini reactions with a mild Lewis acid has been studied. Triggered by metal
      promoted silylation, condensations of aliphatic or aromatic carbonyl compounds
      with appropriately substituted isonitriles capable of neighboring group donation
      afford alpha-hydroxyamides, substituted oxazoles, and other useful heterocycles.

PMID- 11975648
TI  - Determination of unique microbial volatile organic compounds produced by five
      Aspergillus species commonly found in problem buildings.
AB  - This study identified unique microbial volatile organic compounds (UMVOCs)
      produced by five Aspergillus species (A. fumigatus, A. versicolor, A. sydowi, A.
      flavus, and A. niger) cultivated on malt extract agar and gypsum board. The
      hypothesis was that UMVOCs can be used to predict the presence of Aspergillus
      species. During the cultivation humidified air was continually supplied and
      evenly distributed through each of the culture flasks. Volatile metabolites were
      collected using Tenax TA tubes on Days 8, 16, and 30 after inoculation. The
      volatile metabolites were determined by gas chromatography/mass spectroscopy
      after thermal desorption. Nine compounds recognized as UMVOCs--3-methyl-1
      butanol; 2-methyl-1-propanol; terpineol; 2-heptanone; 1-octen-3-ol; dimethyl
      disulfide; 2-hexanone; 3-octanone; and 2-pentylfuran--were found on the cultures
      in detectable amounts. The first two compounds were detected at the highest
      frequency when combining both media. The first four compounds were found to be
      the dominant UMVOCs on gypsum board, which could be used as chemical markers of
      the common Aspergillus species grown indoors.

PMID- 11975650
TI  - Observations of ethical misconduct among industrial hygienists in England.
AB  - Industrial hygienists are uniquely situated to help solve problems in the working
      environment, and failure to behave ethically might have serious and possibly
      fatal consequences. A survey was conducted to estimate the prevalence and nature
      of ethical misconduct within the UK occupational hygiene profession during the
      past 5 years. A postal questionnaire was sent to 50 professional
      industrial/occupational hygienists. Of the 43 respondents, 33 (77%) had witnessed
      activities of potential ethical misconduct in at least one of nine questionnaire
      categories. Additionally, greater than 20% of the hygienists had witnessed at
      least one incident of data fabrication, failure to share credit on work, failure
      to protect confidentiality, criticizing the integrity of another hygienist for
      one's own gain, and plagiarism. The investigation also asked hygienists for their
      opinions on the reasons for breaches as well as potential methods of improvement.

PMID- 11975649
TI  - Replication of human tracheobronchial hollow airway models using a selective
      laser sintering rapid prototyping technique.
AB  - Exposures to toxic or pathogenic aerosols are known to produce adverse health
      effects. The nature and severity of these effects often are governed in large
      part by the location and amount of aerosol deposition within the respiratory
      tract. Morphologically detailed replica hollow lung airway casts are widely used
      in aerosol deposition research; however, techniques are not currently available
      that allow replicate deposition studies in identical morphologically detailed
      casts produced from a common reference anatomy. This project developed a
      technique for the precision manufacture of morphologically detailed human
      tracheobronchial airway models based on high-resolution anatomical imaging data.
      Detailed physical models were produced using the selective laser sintering (SLS)
      rapid prototyping process. Input to the SLS process was a three-dimensional
      computer model developed by boundary-based two-dimension to three-dimension
      conversion of anatomical images from the original National Institutes of
      Health/National Library of Medicine Visible Human male data set. The SLS process
      produced identical replicate models that corresponded exactly to the anatomical
      section images, within the limits of the measurement. At least five airway
      generations were achievable, corresponding to airways less than 2 mm in diameter.
      It is anticipated that rapid prototyping manufacture of respiratory tract
      structures based on reference anatomies such as the Visible Male and Visible
      Female may provide "gold standard" models for inhaled aerosol deposition studies.
      Adaptations of the models to represent various disease states may be readily
      achieved, thereby promoting exploration of pharmaceutical research on targeted
      drug delivery via inhaled aerosols.

PMID- 11975651
TI  - Occupational exposure to bitumen during road paving.
AB  - The exposure of road pavers to total particulates, bitumen fumes, semivolatile
      organic compounds (SVOCs), polycyclic aromatic hydrocarbons (PAHs), low-molecular
      weight amines, styrene, and 1,3-butadiene was studied at 13 paving sites where 11
      different asphalt mixtures were laid. Researchers analyzed 1-hydroxypyrene in the
      workers' pre- and postshift urine samples. The arithmetic mean concentrations of
      total particulates, bitumen fumes, SVOCs, and PAHs in the breathing zone of road
      pavers were 0.6 mg/m3, 0.29 mg/m3, 5.6 mg/m3, and 5.03 microg/m3, respectively.
      The highest bitumen fume concentrations (2.65 mg/m3) were measured in manual
      mastic laying, that is, when the paving temperature was highest. More than 90% of
      air impurities measured were in the vapor phase. Workers laying surface dressing
      were exposed to the highest SVOC concentrations (27.8 mg/m3). The paving
      temperature and the concentrations of bitumen fume correlated positively, but the
      weather conditions significantly affected the workers' exposure; for example,
      increased wind velocity resulted in lower concentrations of SVOCs and PAHs. Job
      title was not found to be a significant determinant of exposure, but exposure to
      bitumen fume and greater than or equal to four-ring PAHs among manual mastic
      pavers, and that to SVOCs and total PAHs among surface dressing workers, were
      significantly higher than among other pavers. Exposure during road paving
      operations was, on average, more than 10-fold higher to PAHs than was the
      exposure of a traffic controller (0.34 microg/m3) caused by automobile exhausts
      from background traffic. The PAHs were comprised mainly of two- and three-ring
      compounds. The concentrations of amines, and impurities from polymer modified
      bitumens, styrene, and 1,3-butadiene were below detection limits. Urinary 1
      hydroxypyrene concentrations were higher among road pavers than among office
      workers serving as referents.

PMID- 11975652
TI  - Exposure to wood dust and heavy metals in workers using CCA pressure-treated
      wood.
AB  - Chemical pesticide treatment enables relatively nonresistant woods to be used in
      outdoor construction projects. The most prevalent procedure used to protect these
      woods is pressure treatment with chromium, copper, and arsenic (CCA). This pilot
      study examined the airborne concentration and particle size distribution of wood
      particles, chromium, copper, and arsenic at both outdoor (measured over the whole
      work day) and indoor (measured during the performance of specific tasks) work
      sites. At the outdoor residential deck construction sites, the arithmetic mean
      total dust concentration, measured using personal filter cassette samplers, was
      0.57 mg/m3. The mass median aerodynamic diameter (da) of the outdoor wood dust
      was greater than 20 microm. Indoor wood dust concentrations were significantly
      greater than those measured outdoor and were job category-dependent. The highest
      mean breathing zone dust concentration, 49.0 mg/m3, was measured at the indoor
      sanding operation. Personal impactor sampling demonstrated that the mean total
      airborne concentration of arsenic, but not chromium or copper, was consistently
      above recommended occupational exposure levels at the indoor work site, and
      occasionally at the outdoor work sites. At the indoor sanding operation, the mean
      total chromium, copper, and arsenic concentrations were 345, 170, and 342
      microg/m3, respectively. Thus, significant exposure to airborne heavy metals can
      occur as a result of indoor and outdoor exposure to CCA pressure-treated wood
      dust. Therefore, current standards for wood dust may not adequately protect
      workers from the heavy metals commonly used in CCA pressure-treated wood.

PMID- 11975653
TI  - A comprehensive investigation of noise exposure in and around an integrated iron
      and steel works.
AB  - A comprehensive environmental noise exposure study was carried out in and around
      a major iron and steel works. The works was located in the central part of the
      city and was surrounded by residential, commercial, and sensitive receptors.
      Traffic activity near the plant was significant and added to the background noise
      level. Considering the variety of noise sources in the plant area and in the
      neighborhood, a practical approach to measure noise equivalent level in the plant
      and in the residential, commercial, industrial, and silence zone was adopted. A
      modular precision integrating sound level meter with statistical analyzer module,
      octave filter set, and calibrator were used during the measurements. The day and
      night level, Ldn, was determined. Worker exposure was assessed by determining the
      speech interference level (SIL), loudness level, and noise rating level at one of
      the major sources located in the power plant of the steel works. The results
      indicate that SIL was 94 dBA, loudness level was 112 phons, and the noise rating
      was in the range of 85-95. A traffic noise index also was determined near the
      works gates and was in the range of 68-96. The impact on the community is
      significant as observed from Ldn levels. Some mitigation measures for noise
      control are also discussed.

PMID- 11975654
TI  - UV disinfection of soluble oil metalworking fluids.
AB  - The efficacy of a new high-intensity germicidal ultraviolet (UV) lamp for
      disinfection of opaque metalworking fluids (MWF) was investigated under
      laboratory conditions. Three dilutions of "soluble oil" MWF and water controls in
      a circulating system were inoculated with suspensions of Pseudomonas fluorescens
      to an initial concentration of about 10(7) colony forming units (CFU) per
      milliliter and irradiated with a submerged nonglass UV lamp. Aliquots of the
      circulating fluid were withdrawn before irradiation and at 10-sec intervals in
      the water control and 10-min intervals in the MWF. The samples were diluted with
      sterile water, plated, and counted after 18-24 hours' incubation. The UV-C
      radiation output of the lamp was estimated by irradiance measurements using a
      research radiometer. The concentration of CFU decreased by at least 2 logs (>99%
      reduction in culturability) in 30 sec in irradiated water. In all three dilutions
      of MWF, a 2-log decrease was obtained within 60 min. The UV-C output of the lamp
      was estimated at about 6 W. The disinfection appeared to follow a first order
      rate law both in MWF and in water. The CFU concentration was stable over time in
      unirradiated controls. These results demonstrate that UV disinfection is feasible
      in MWF opaque to both visible and UV wavelengths of light.

PMID- 11975655
TI  - Styrene emissions from the spray-up and vacuum injection processes--a
      quantitative comparison.
AB  - Styrene emissions were studied during manufacturing of two identical glass-fiber
      reinforced plastic boats by two different manufacturing methods. The
      manufacturing methods were spray-up, which is an open method, and vacuum
      injection, which is a closed method. Changing the manufacturing process from an
      open method to a closed method decreased the styrene evaporation dramatically in
      this particular case. By using vacuum injection, the styrene emission during the
      laminate application was reduced by 98% compared with the styrene emission during
      laminate application by spray-up. Gel coat application by spraying will remain a
      major source for styrene emissions. The greatest environmental benefit is
      achieved with closed manufacturing methods when products without gel coat are
      made. The whole manufacturing process can then be performed in a closed system
      virtually free from emissions.

PMID- 11975656
TI  - A review of fluid replacement for workers in hot jobs.
AB  - Prolonged work in hot environments leads to progressive water and electrolyte
      loss from the body. The rate of sweating varies among individuals and depends on
      the environmental conditions, but in protective clothing and very hot
      environments rates can reach 2.25 L/hour. Because hypohydration will impair work
      performance and increases the risk of heat injury, consumption of fluids is
      necessary to prevent dehydration and enhance performance. Much of the research on
      rehydration has been conducted in athletic settings. The purpose of this review
      is to interpret the existing research literature on hydration in a way that is
      useful to industrial hygienists and safety experts. The authors hope to provide
      industrial hygienists and safety professionals with scientific bases for making
      recommendations regarding beverage availability and hydration practices. Although
      water is a very common beverage, some previous research has reported that drinks
      containing low to moderate levels of electrolytes and carbohydrates may provide
      some significant advantages in industrial situations. In general these studies
      seem to support the use of electrolyte-carbohydrate beverages as a supplement to
      water or as a replacement for water.

PMID- 11975657
TI  - Hearing protector use in noise-exposed workers: a retrospective look at 1983.
AB  - Although hearing protectors have been available for more than 60 years, little
      field surveillance has been done to assess their appropriate wear in noisy
      occupational environments. This study examined historical field survey data to
      determine whether workers use hearing protection when exposed to loud noise. Data
      from the 1981-83 NIOSH National Occupational Exposure Survey were analyzed to
      determine whether workers in noise greater than or equal to 85 dBA were using
      hearing protection. The study also looked at the effect of company personal
      protective equipment (PPE) policies on hearing protector compliance. This study
      found that, in 1981-83, an estimated 4.1 million industrial workers were exposed
      to noise greater than or equal to 85 dBA. Of these, 41% were wearing some form of
      hearing protection. This percentage varied from 79% of workers exposed in SIC 76
      (Miscellaneous Repair Service) to less than 1% in Communications (SIC 48),
      Wholesale Trade Nondurable Goods (SIC 51), and Automotive Dealers & Service
      Stations (SIC 55). Whether an establishment had a written policy on wearing PPE
      seemed to make no difference, because there appeared to be no tie between the
      percentage of workers wearing of hearing protection and presence of a PPE policy.

PMID- 11975658
TI  - Exposure databases and exposure surveillance: promise and practice.
AB  - Based on recent developments in occupational health and a review of industry
      practices, it is argued that integrated exposure database and surveillance
      systems hold considerable promise for improving workplace health and safety. A
      foundation from which to build practical and effective exposure surveillance
      systems is proposed based on the integration of recent developments in electronic
      exposure databases, the codification of exposure assessment practice, and the
      theory and practice of public health surveillance. The merging of parallel, but
      until now largely separate, efforts in these areas into exposure surveillance
      systems combines unique strengths from each subdiscipline. The promise of
      exposure database and surveillance systems, however, is yet to be realized.
      Exposure surveillance practices in general industry are reviewed based on the
      published literature as well as an Internet survey of three prominent industrial
      hygiene e-mail lists. Although the benefits of exposure surveillance are many,
      relatively few organizations use electronic exposure databases, and even fewer
      have active exposure surveillance systems. Implementation of exposure databases
      and surveillance systems can likely be improved by the development of systems
      that are more responsive to workplace or organizational-level needs. An overview
      of exposure database software packages provides guidance to readers considering
      the implementation of commercially available systems. Strategies for improving
      the implementation of exposure database and surveillance systems are outlined. A
      companion report in this issue on the development and pilot testing of a
      workplace-level exposure surveillance system concretely illustrates the
      application of the conceptual framework proposed.

PMID- 11975659
TI  - Development and piloting of an exposure database and surveillance system for DOE
      cleanup operations. Department of Energy.
AB  - An industrial hygiene exposure database and surveillance system was developed in
      partnership between National Institute for Occupational Safety and Health (NIOSH)
      funded independent investigators and practicing industrial hygienists at the
      Rocky Flats Environmental Technology Site (RFETS) in Golden, Colo. RFETS is a
      former U.S. Department of Energy nuclear weapons plant that is now in cleanup
      phase. This project is presented as a case study in the development of an
      exposure database and surveillance system in terms that are generalizable to most
      other industries and work contexts. Steps include gaining organizational support;
      defining system purpose and scope; defining database elements and coding;
      planning practical and efficient analysis strategies; incorporating reporting
      capabilities; and anticipating communication strategies that maximize the
      probability that surveillance findings will feed back to preventive applications.
      For each of these topics, the authors describe both general considerations as
      well as the specific choices made for this system. An important feature of the
      system is a two-tier task-coding scheme comprising 33 categories of task groups.
      Examples of grouped analyses of exposure data captured during the system pilot
      period demonstrate applications to exposure control, medical surveillance, and
      other preventive measures.

PMID- 11975660
TI  - Benzene in gasoline and crude oil: occupational and environmental implications.
AB  - A review of studies, published in peer-reviewed journals and articles available
      as technical reports of various organizations, regarding benzene in gasoline and
      crude oil was performed. The summarized data will be useful for retrospective
      exposure assessments in epidemiological studies. It shows that in the past,
      benzene in gasoline has been quite high, but now, there is a distinct trend in
      North America and Europe to reduce benzene in gasoline to a level of about 1%.
      The reduction of benzene in gasoline results not only in the lowering of
      occupational exposure for workers, but it also has far greater influence in
      decreasing the environmental benzene exposure for the general public.

PMID- 11975661
TI  - High-frequency noise in dentistry.
AB  - Earlier studies have revealed that dentists have higher hearing thresholds than
      expected. The aim of this study was to evaluate the noise levels of current
      dentistry equipment under very controlled conditions. This noise study was
      carried out in the Acoustics Laboratory of Kuopio Regional Institute of
      Occupational Health, the background noise of which is about 0 dB(A). Working
      noise was simulated by drilling a polyacetal plate. During drilling and idling,
      the noise of the hand pieces was measured over a reflecting plane on the
      hemisphere surface, the radius of which was 0.3 m, and 10 noise samples were
      picked for each hand piece. The average sound pressure level and the sound power
      level of the devices were calculated applying the standard ISO 3744. The
      measurement and analysis were done in the one-third octave bands of 25-80,000 Hz.
      The measuring instruments used were the B&K 4135 microphones, the B&K 2633
      preamplifiers, the B&K 2811 multiplexer, and the B&K 2133 real-time analyzer with
      the ZT 0318 high-frequency expansion unit. During the simulated work, the average
      A-weighted sound pressure level of the new and old hand pieces was 76-82 dB(A),
      that of the power suction tube 77 dB(A), the saliva suction tube 75 dB(A), and
      the ultrasonic scaler 83 dB(A). The average ultrasound level of the ultrasonic
      scaler was 107 dB at the one-third octave band of 25,000 Hz.

PMID- 11975662
TI  - A tracer method for evaluating recirculation of pollutant releases in buildings.
AB  - A method is introduced for evaluating recirculation in a building ventilation
      system from pollutant emissions in or near the building. Tracer was released at a
      known rate at the point of pollutant emission. Using measured tracer
      concentrations, the tracer release rate, and an estimate of the pollutant release
      rate, pollutant concentrations were estimated at the locations in the building
      where the tracer was measured. The method can be used to test whether a
      ventilation system is adequate for maintaining an acceptable work environment
      before work with a hazardous substance begins. In a case study presented to
      illustrate the technique, initial attempts to correct a problem of recirculation
      of sulfuric acid from a fume hood in a chemistry laboratory were shown to be
      inadequate, prompting the ventilation contractor to make further repairs before
      work with sulfuric acid could be resumed.

PMID- 11975664
TI  - Are Polish and Swedish dental graduates adequately prepared for dental practice
      in the UK? A discussion of the transferability of general dental practitioners in
      Europe.
AB  - In the context of European Union harmonization, this article compares the systems
      of training for general dental practice in three European countries, the UK,
      Sweden and Poland. A UK perspective is adopted and the question as to whether
      dentists who have qualified in Poland or Sweden are adequately prepared for
      practice in the UK is explored. The paper is a result of discussion between
      providers of dental training in the three study countries. Key similarities,
      strengths and weaknesses are identified and issues pertinent to the
      transferability of general dental practitioners within Europe are raised.

PMID- 11975663
TI  - Fructosamine 3-kinase is involved in an intracellular deglycation pathway in
      human erythrocytes.
AB  - Fructosamine 3-kinase, which phosphorylates low-molecular-mass and protein-bound
      fructosamines on the third carbon of their deoxyfructose moiety, is quite active
      in erythrocytes, and was proposed to initiate a process removing fructosamine
      residues from proteins. In the present study, we show that incubation of human
      erythrocytes with 200 mM glucose not only caused the progressive formation of
      glycated haemoglobin, but also increased the level of an anionic form of
      haemoglobin containing alkali-labile phosphate, to approx. 5% of total
      haemoglobin. 1-Deoxy-1-morpholinofructose (DMF), a substrate and competitive
      inhibitor of fructosamine 3-kinase, doubled the rate of accumulation of glycated
      haemoglobin, but markedly decreased the amount of haemoglobin containing alkali
      labile phosphate. The latter corresponds therefore to haemoglobin bound to a
      fructosamine 3-phosphate group (FN3P-Hb). Returning erythrocytes incubated with
      200 mM glucose and DMF to a low-glucose medium devoid of DMF caused a decrease in
      the amount of glycated haemoglobin, a transient increase in FN3P-Hb and a net
      decrease in the sum (glycated haemoglobin+FN3P-Hb). These effects were prevented
      by DMF, indicating that fructosamine 3-kinase is involved in the removal of
      fructosamine residues. The second step of this 'deglycation' process is most
      likely a spontaneous decomposition of the fructosamine 3-phosphate residues to a
      free amine, 3-deoxyglucosone and P(i). This is consistent with the findings that
      2-oxo-3-deoxygluconate, the product of 3-deoxyglucosone oxidation, is formed in
      erythrocytes incubated for 2 days with 200 mM glucose in a sufficient amount to
      account for the removal of fructosamine residues from proteins, and that DMF
      appears to inhibit the formation of 2-oxo-3-deoxygluconate from elevated glucose
      concentrations.

PMID- 11975666
TI  - Orthodontic undergraduate education: developments in a modern curriculum.
AB  - This paper explores some modern concepts of teaching and learning, including
      cognitive theory, the zone of proximal development, constructivism, andragogy and
      learning styles and describes how they have informed the development of an
      undergraduate orthodontic curriculum. The changes described include student
      centred learning, guided self-learning, and the incorporation of problem-based
      learning concepts. The details of the problem-based learning programme are
      described together with results of student feedback on the change in teaching and
      learning style.

PMID- 11975667
TI  - Rating of statements in an internal course evaluation: comparison between
      different groups of assessors.
AB  - The increased concern for accountability and quality improvement is inducing
      universities throughout Europe to evaluate and control performance. The
      establishment of criteria for educational quality, a requirement for a successful
      evaluation, was studied as part of an evaluation of the dental education
      programme at the Catholic University of Leuven. Criteria suggested by different
      groups (members of the internal evaluation commission including graduate and
      postgraduate students; members of the academic staff of the School of Dentistry,
      Oral Pathology and Maxillo-facial Surgery, and other members of the academic
      staff, not directly belonging to the school), were analysed by means of ANOVA
      with Scheffe posthoc tests to identify intergroup differences. It was
      hypothesized that a closer connection to the dental curriculum or a higher
      responsibility in the evaluation process would result in stricter criteria. For
      108 different questions (in the form of statements with a six point Likert-type
      scale), members of the three groups had to indicate the score below which the
      quality would be considered suboptimal. Except for one question, no significant
      differences were found between ratings given by the members of the internal
      evaluation commission and other members of the School. Significant differences
      were found between non-school members and school- and/or commission-members. This
      study indicates that agreement on educational quality may be presupposed within
      an academic faculty and between members of the internal evaluation commission.
      However, the study also indicated that some caution should be exercised when
      'external' teachers are included in the evaluation process.

PMID- 11975668
TI  - Is there a link between writing ability, drawing aptitude and manual skills of
      dental students?
AB  - In France, students have to choose between medical or dental courses, according
      to their rank, after a competitive examination at the end of their first year of
      study. Intellectual ability is evaluated, while manual competence is not, and
      this is a paradox. The purpose of the present study is to investigate whether it
      is possible to predict the manual aptitude of a dental student through tests that
      allow the qualities of reflection and organization to be judged. We administered
      writing tests and drawing tests to 45 students of the Bordeaux dental school to
      ascertain whether there was a correlation between the competitive examination,
      the criterion examined (reflection, organization, aesthetics em leader) and the
      results of the dental practical assessments during the first year of dental
      study. The results showed that although manual competence in dental practical
      work, graphic qualities and writing skills are connected, it is difficult to
      correlate them directly with competitive examination performance. In view of the
      number of uncontrolled variables influencing the students' outcome, is it useful
      to be able to predict who will become a good practitioner? One indication may be
      found in the moral reasoning of candidates.

PMID- 11975669
TI  - Preventive practice of Mongolian dental students.
AB  - To investigate the preventive practice of Mongolian dental students, in relation
      to their knowledge of preventive care, self-perceived competency, oral self-care,
      and dental health status, a questionnaire was distributed to all (n = 79)
      clinical-year students of The Dental School of the Mongolian National Medical
      University. Dental students' reported preventive practice was explained by their
      knowledge of preventive care (P = 0.002) and self-perceived competency (P =
      0.002), whereas their study-year, oral self-care, and dental health status,
      expressed as the Tissue Health Index (THI), remained statistically non
      significant in the linear regression model. This explained 28% of the variation
      in the parameters examined. In logistic regression analysis, a student's study
      year (OR = 2.5), knowledge of preventive care (OR = 1.1), and THI (OR = 1.8) were
      related to their highest scores on preventive practice. Preventive practice among
      Mongolian dental students could be improved by increasing their knowledge,
      particularly in modern methods for caries-prevention such as fluoride, sealants,
      and xylitol. Preventive methods should be integrated into all topics of the
      dental curriculum and the learning environment should support such training for
      future oral health professionals.

PMID- 11975671
TI  - Gynecologic oncology: a discipline or a profession?

PMID- 11975672
TI  - Palliative management of malignant bowel obstruction.
AB  - Bowel obstruction may be a mode of presentation of intra-abdominal and pelvic
      malignancy or a feature of recurrent disease following anticancer therapy.
      Malignant bowel obstruction is well-recognized in gynecologic patients with
      advanced cancer. Retrospective and autopsy studies found the frequency at
      approximately 5-51% of patients with gynecological malignancy(1-7). Malignant
      bowel obstruction (MBO) is particularly frequent in patients with ovarian cancer
      where it is the most frequent cause of death(7). Patients with stage III and IV
      ovarian cancer and those with high-grade lesions are at higher risk for MBO as
      compared to patients with lower stage or low-grade tumors(1,8). Ovarian carcinoma
      accounted for 50% of small bowel obstruction and 37% of large bowel obstruction
      treated in a large gynecological oncology service(8-11).

PMID- 11975673
TI  - Preoperative selection of patients with low-stage endometrial cancer at high risk
      of pelvic lymph node metastases.
AB  - The goal of this study was to determine diagnostic accuracy of preoperative
      transvaginal sonography (TVS) to assess myometrial infiltration in patients with
      endometrial cancer and to determine the possibility of preoperatively selecting
      low-stage endometrial cancer patients at high risk of lymph node metastases. The
      depth of myometrial infiltration of endometrial cancer was assessed using TVS
      before or after curettage. Infiltration was classified as superficial if less
      than half of the myometrium was involved, otherwise it was classified as deep
      infiltration. Results were compared with the histology results of the definitive
      specimens. Patients were classified as high risk when they satisfied two of the
      following three criteria: 60 years of age or older; deep myometrial infiltration;
      and poorly differentiated or undifferentiated tumor. A total of 93 patients from
      11 clinics were analyzed. The mean age was 66.1 years (SD +/- 11.4). The
      sonography and histology findings were in agreement in 69 of 93 patients. The
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV), of "deep infiltration" by preoperative TVS were 79% (95%
      CI 0.65-0.93), 72% (95% CI 0.61-0.83), 61% (95% CI 0.46-0.75), and 86% (95% CI
      0.76-0.96), respectively. Combining tumor grade and myometrial infiltration in
      the hysterectomy specimen and age, 30 of 81 patients were classified as high-risk
      patients. Sensitivity and PPV, specificity, and NPV for preoperative diagnosis of
      high risk were 80% (95% CI 0.65-0.94) and 88% (95% CI 0.79-0.97), respectively.
      Preoperative assessment of myometrial tumor infiltration using just TVS is only
      moderately reliable in endometrial cancer patients. If the results of TVS,
      however, are combined with the patient's age and the degree of tumor
      differentiation in curettings, it is possible to preoperatively select
      endometrial cancer patients with a high risk of pelvic lymph node metastases with
      sufficient reliability.

PMID- 11975674
TI  - The prognostic value of a histologic grading system, DNA profile, and MIB-1
      expression in early stages of cervical squamous cell carcinomas.
AB  - This study evaluated the prognostic importance of a new grading system focusing
      on the invasive tumor front, DNA profile, and the proliferation marker MIB-1. A
      complete geographic series of 172 women treated with radical hysterectomy
      (Wertheim-Meigs) for FIGO stage I-II cervical carcinomas was the target
      population. The analyses were performed on 141 (82%) squamous cell carcinomas of
      the complete series. During the period of observation (mean 222 months), 17
      recurrences (12.1%) were encountered. Prognostic factors for disease-free
      survival were lymph node status (P < 0.000001), radical surgical margins (P =
      0.00004), and tumor size (P = 0.002). The complete score of the invasive front
      grading system (IFG), and the individual scores of two variables-pattern of
      invasion and host response-were all significantly (P = 0.002, P = 0.007, P =
      0.0001) associated with pelvic lymph node metastases. Host response was the
      single most important factor in the IFG system, and it was superior to the
      complete score in predicting lymph node metastases. The total IFG score was also
      a significant (P = 0.003) prognostic factor for disease-free survival. DNA
      ploidy, S-phase fraction, and MIB-1 expression were nonsignificant factors in
      predicting pelvic lymph node metastases and disease-free survival of the patient.
      The IFG in the original or modified versions could predict low- and high-risk
      groups of tumors and therefore be of value in treatment planning for these
      patients.

PMID- 11975675
TI  - Pathologic complete remission after preoperative intracavitary radiotherapy of
      cervical cancer stage Ib and IIa is a strong prognostic factor for long-term
      survival: analysis of the Radiumhemmet data 1989-1991.
AB  - The purpose of this study was to evaluate the treatment results of preoperative
      brachytherapy and the prognostic value of pathologic complete remission after
      preoperative intracavitary irradiation in patients with stage Ib and IIa cervical
      carcinoma in relation to recurrence rate and survival. The clinical records of
      185 patients with stage Ib (129 patients) and IIa (56 patients) cervical
      carcinoma, consecutively admitted to Radiumhemmet from January 1989 to December
      1991 were reviewed. The median follow-up time was 71 months. In 121 patients the
      treatment consisted of uterovaginal intracavitary irradiation, according to the
      Stockholm technique, followed by surgery. Tumor remission assessed in the
      surgical specimen was classified as pathologic complete remission (pCR) if no
      microscopic tumor was found or incomplete pathologic remission (non-pCR) if
      microscopic residual tumor was found. Postoperative external beam radiation was
      added to cases with metastases in pelvic nodes or residual tumor in the resection
      margins. The disease-specific 5-year survival was 87% and 75% for stage Ib and
      IIa, respectively, for the patient population treated with preoperative
      intracavitary radiotherapy and surgery. After intracavitary radiation, 79% of the
      patients obtained pCR of the primary tumor. Five-year survival in those with pCR
      was 95%, compared with 46% in those with non-pCR (P < 0.0001). Patients with pCR
      and no lymph node metastases had a 98% 5-year survival as compared to a 5-year
      survival of 64% in patients with non-pCR and node negativity (P < 0.0001).
      Locoregional relapses were diagnosed in 2% of the patients with pCR compared to
      54% in patients with non-pCR (P < 0.0001). Multivariate analysis revealed non-pCR
      (RR = 6.42) and node positivity (RR = 4.59) as nonfavorable factors for survival,
      while tumor size was not found to be of independent significance for survival.
      Pathologic complete remission after intracavitary irradiation is a strong
      favorable prognostic factor in node-negative patients. The combination of
      preoperative intracavitary radiotherapy and surgery results in a high cure rate
      and aids in identifying patients at risk for relapse who might be subject to
      adjuvant therapy.

PMID- 11975676
TI  - A research-based tumor tissue bank of gynecologic oncology: characteristics of
      nucleic acids extracted from normal and tumor tissues from different sites.
AB  - This article describes a gynecology and pathology-oriented tumor tissue bank that
      is approaching the research requirements of modern molecular oncology and
      compared characteristics of nucleic acids extracted from preserved tissues.
      Through August 2000, 8869 specimens, including fresh neoplastic tissues and
      normal counterparts, body fluids (ascites, tumor content, and blood), and
      cervical scrapings, were procured from 1853 patients. DNA and RNA were extracted
      from a random sampling of normal (n = 50) and tumor (n = 53) tissues from the
      uterine cervix (n = 47), endometrium (n = 24), and ovary (n = 32). As expected,
      tumor tissues conferred a higher yield of DNA (1.56 +/- 1.24 versus 0.94 +/- 0.72
      microg/mg tissue, P = 0.001) and RNA (5.04 +/- 6.21 versus 2.12 +/- 1.76
      microg/ml, P < 0.001) than normal tissues. However, the RNA message abundance, as
      measured by RNA yield/DNA yield, was not different between tumor and normal
      tissues. With a similar content of DNA in the endometrium, uterine cervix, and
      ovary, RNA yield was higher in the endometrium than the others (P = 0.013). In
      tumors from these three sites, similar yields of DNA and RNA were noted. Overall
      the yield of DNA remained unchanged from specimens preserved for as long as 7
      years, although at this length of storage, RNA yield became lower and variable.
      This study provides the basic characteristics of nucleic acids derived from
      normal and tumor tissues and ensures future research utility of these frozen
      specimens.

PMID- 11975677
TI  - Morphologic evaluation of the antitumor activity of photodynamic therapy (PDT)
      using mono-L-aspartyl chlorin e6 (NPe6) against uterine cervical carcinoma cell
      lines.
AB  - In order to elucidate the antitumor effect and mechanism of action of
      photodynamic therapy (PDT) using the photosensitizing agent mono-L-aspartyl
      chlorin e6 (NPe6) and a semiconductor laser, we conducted a morphologic study on
      uterine cervical cancer cell lines. First, tumor shrinkage was confirmed in a
      tumor growth inhibition test. Next, morphologic changes after PDT were examined,
      and since the major change appeared to be tumor necrosis secondary to obstruction
      of the blood vessels around the tumor, an NPe6 cell uptake experiment was
      performed. The results confirmed that a significantly greater amount of NPe6 was
      incorporated by human umbilical vein endothelial cells (HUV-EC1) and the cervical
      cancer cell lines than by human umbilical cord-derived fibroblasts. Based on
      these findings it was concluded that NPe6 possesses tumor affinity, and necrosis
      secondary to vascular obstruction was postulated to be the principal mechanism of
      the antitumor effect of PDT using NPe6.

PMID- 11975678
TI  - Adjuvant pelvic irradiation in patients with pathologic T2b carcinoma of the
      uterine cervix.
AB  - Patients with cervical cancer are subject to postoperative adjuvant therapy if
      the histopathologic examination reveals parametrial involvement. This study
      evaluated the patterns of failure in patients with pathologic parametrial
      invasion (pT2b) treated with adjuvant pelvic irradiation. Between April 1985 and
      March 1997, 45 patients with pT2b cervical cancer were treated with postoperative
      pelvic irradiation. The median age was 52 years. Preoperative clinical stages
      were stage Ib in 8 patients, IIa in 4, and IIb in 33. Twenty-three patients had
      lymph node metastasis. The median total dose of whole pelvic radiation therapy
      was 50 Gy. Occurrence of pelvic failure or distant metastasis according to the
      nodal status was examined. None of the 22 patients without lymph node metastasis
      developed distant metastasis. Among the 23 node-positive patients, 6 developed
      distant metastasis as an initial failure site. The 5-year overall survival of the
      entire group was 78%. The actuarial distant metastasis-free rates at 5 years were
      73% and 100% for those with and without pelvic lymph node metastasis,
      respectively (P = 0.016). Results support previous evidence for chemoradiation in
      patients with pelvic lymph node metastasis. However, it appears that the role of
      systemic chemotherapy for node-negative pT2b patients is yet to be established.

PMID- 11975679
TI  - Microsatellite instability in gonadal tumors of XY pure gonadal dysgenesis
      patients.
AB  - To investigate genetic alternation accompanied by malignant transformation in
      gonadal tumors of XY pure gonadal dysgenesis patients, we investigated
      microsatellite instability in the hMSH1, hMSH2, TP53, and DCC loci, and ras
      mutations in two patients. The gonadal tumors from the patients were combined
      gonadoblastoma and dysgerminoma. Microsatellite instability and/or loss of
      heterozygotes (LOH) at hMSH1, hMSH2, and TP53 were detected in the dysgerminoma
      lesions of the both patients, but were not observed in any normal tissues. In the
      analyses of the H-, K-, or N-ras genes, where specific mutations have been
      frequently reported, no mutations were observed in the tumors. It is suggested
      therefore that microsatellite instability plays an important role in malignant
      transformation of gonadal tumors in patients with XY pure gonadal dysgenesis.

PMID- 11975680
TI  - Loss of heterozygosity at chromosome 3p in epithelial ovarian cancer in China.
AB  - The aim of this investigation was to determine the relationship between 3p loss
      of heterozygosity (LOH) and the pathogenesis of ovarian cancer. Fifty cases of
      epithelial ovarian tumor, including 40 cases with malignant tumors and 10 cases
      with benign tumors, were examined by polymerase chain reaction (PCR) with D3s1228
      and D3s1038 microsatellite polymorphism markers at 3p. Thirty-two of the 40 cases
      (80%) with ovarian cancer showed LOH at 3p14 or 3p25, but only 1 of 10 cases
      (10.0%) with benign ovarian tumor showed 3p LOH. Among them, 24 cases (60.0%) had
      LOH at 3p14 and 16 cases (40.0%) at 3p25, as well as 8 cases (20.0%) with
      codeletion on both 3p14 and 3p25. According to FIGO staging, the frequency of LOH
      at 3p in ovarian cancer patients with stage IIIa or IIIb was higher than that in
      patients with stage I or II (P < 0.05), but there was no relationship between 3p
      LOH and the pathologic types in epithelial ovarian cancer (P > 0.05). Since 3p
      LOH commonly occurs in epithelial ovarian cancer and LOH at 3p14 and 3p25
      correlates to the staging of ovarian cancer, it is suggested that there are some
      candidate ovarian TSGs harbored in the 3p region and that the detection of 3p
      LOHs may be used as a genetic marker for monitoring the development of ovarian
      cancer.

PMID- 11975681
TI  - Activity of ALRT 1550, a new retinoid, with interferon-gamma on ovarian cancer
      cell lines.
AB  - Retinoids have been shown to be effective regulators of cell proliferation and
      differentiation in many human cancers. The major biologic activity of the
      retinoids is mediated by two families of nuclear receptors: retinoic acid
      receptors (RARs) and retinoid X receptors (RXRs). ALRT 1550 is one of the most
      potent RAR selective retinoids discovered to date, with 10-100 times more
      activity than ATRA in competitive binding and cotransfection assays and 300 times
      more inhibiting activity against proliferation of cervical carcinoma cell. To
      evaluate the role of ALRT 1550 in ovarian cancer, the growth inhibitory activity
      of ALRT 1550 was determined in the ATRA-resistant ovarian cancer cell line SKOV-3
      and ovarian cancer cell line 2774 after exposure to concentrations of 0.1, 1,
      2.5, 5, and 10 microM for 7 days. SKOV-3 showed 51%, 53%, and 68% cell growth
      inhibition after treatment with ALRT 1550 at concentrations of 2.5, 5, and 10
      microM, respectively, and the 2774 cell line showed 46% inhibition after
      treatment at 10 microM. Because interferon (IFN)-gamma was found to
      synergistically amplify the growth inhibition of retinoids in cultured breast
      cancer cells, we investigated the combination of ALRT 1550 with IFN-gamma in two
      ovarian cancer cell lines. ALRT 1550 (5 microM) in combination with IFN-gamma at
      a concentration of 500 U/ml inhibited cell growth of SKOV-3 by as much as 81% (CI
      = 1.88). This is a 28% greater effect than with ALRT alone. Cell line 2774 showed
      a 69% cell growth inhibitory effect with ALRT 1550 (5 microM) in combination with
      IFN-gamma at a concentration of 1000 U/ml (CI = 1.03). ALRT 1550 and IFN-gamma
      may act synergistically in the SKOV-3 ovarian cancer cell line and additively in
      the 2774 cell line. In conclusion, ALRT 1550 may be a promising drug with a high
      biologic modulating activity against ovarian cancer. In combination with IFN
      gamma, additive and perhaps synergistic effects may be seen in some ovarian
      cancer cell lines. Combining these two biologic modifiers for the treatment of
      ovarian cancer may lower the effective dose of the retinoids, thus decreasing
      their side effects.

PMID- 11975682
TI  - Pulmonary metastasis from endometrial carcinoma.
AB  - The objective of this article is to investigate the clinical features of
      pulmonary metastasis (PM) from endometrial adenocarcinoma, in particular, the
      predictors of prolonged survival after PM detection. Fifteen patients who
      developed PM and underwent chest computed tomography (CT) scans for evaluation of
      PM were studied: 12 patients with pulmonary recurrence and 3 patients with PM on
      presentation. All patients with bilateral nodules or lymphangitic spread had
      metastases in other sites prior to or concomitant with PM, most of which were
      detected in para-aortic lymph nodes and/or the vaginal wall, while only one of
      five patients with a limited number (n < or = 5) of unilateral nodules had these
      metastases. The median survival time for the 10 patients with bilateral PMs was
      significantly shorter than that of the 5 patients with a limited number of
      unilateral nodules who were treated with surgery (7 versus 50 months, P = 0.005).
      Patients who developed pulmonary recurrence 2 years after the initial therapy had
      a significantly longer survival than those who developed it within 2 years (31
      versus 10 months, P = 0.01). In conclusion, the distribution of PM determined by
      CT scans and the time interval between the initial therapy and the detection of
      pulmonary recurrence are the predictors of survival after PM detection.

PMID- 11975683
TI  - Use of herbs in women diagnosed with ovarian cancer.
AB  - Of 113 consecutive ovarian cancer patients identified in a gynecologic clinic in
      a major academic medical center in San Francisco, 41 patients were successfully
      contacted, were eligible, and participated in a telephone survey. We contacted
      women identified consecutively in the clinic database as having ovarian cancer
      and sent a letter introducing our research team and asking for help. Members of
      the research team then contacted the women to conduct the telephone interviews.
      Fifty-one percent (95% CI 35-67) of the women had taken herbs sometime since they
      were diagnosed with ovarian cancer. Most herb uses occurred concurrently with
      chemotherapy. Only 12% (95% CI 4-26) used an herbalist or other health
      practitioner for guidance in herb use. Only one woman took herbs instead of
      chemotherapy. A large number of women attending our practice in the San Francisco
      Bay area use herbs as complementary medicine during their cancer treatment.

PMID- 11975684
TI  - Transurethral retrieval of a proximally dislodged ureteral stent.
AB  - A proximally migrated ureteral stent into the renal pelvis is an uncommon problem
      that poses a difficult technical challenge. A 32-year-old woman had her ureteral
      stent inadvertently dislodged into the renal pelvis at the time of stent
      exchange. The stent was successfully retrieved and repositioned transurethrally
      with a snare fed through the left ureter and into the renal pelvis. This is a
      relatively noninvasive method of retrograde retrieval of a proximally dislodged
      ureteral stent.

PMID- 11975685
TI  - Squamous cell vulvar carcinoma associated with Fanconi's anemia: a case report.
AB  - Fanconi's anemia (FA) is a rare autosomal recessive syndrome associated with a
      strong predisposition to cancer, particularly squamous cell carcinoma (SCC) of
      various organs. A few cases of lower genital tract neoplasia have been described.
      We present a 14-year-old black girl with an advanced squamous cell vulvar
      carcinoma treated with cisplatin chemotherapy plus radiation therapy. The patient
      died because of fungal sepsis. Polymerase chain reaction (PCR) was positive to
      human papillomavirus (HPV)-16. Vulvar carcinoma is a very rare condition in
      teenagers, but the association of Fanconi's anemia and SCC of many sites is
      common. Vulvar carcinoma when associated with Fanconi's anemia is a great
      treatment challenge.

PMID- 11975686
TI  - Malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine
      differentiation.
AB  - Malignant mixed Mullerian tumors (MMMTs) are rare neoplasms. We report the
      clinical, pathologic, and immunohistochemical features of an MMMT primary of
      uterine cervix. This lesion was composed of a poorly differentiated epithelial
      component (cytokeratin positive) and a spindle cell component (vimentin positive)
      with heterologous (myoblastic) differentiation (focal 1A4 positive). There were
      also cells with neuroendocrine features that expressed S-100 and chromogranin A.
      Along with a brief review of this amazing neoplasm, some histogenetic concepts
      relevant to this case are discussed. To our knowledge this is the first report of
      a malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine
      differentiation.

PMID- 11975687
TI  - Angiomyofibroblastoma of the vulva.
AB  - A case of angiomyofibroblastoma of the vulva in a 53-year-old woman was examined
      by means of immunohistochemistry. Histological examination of the tumor revealed
      typical characteristics of vulval angiomyofibroblastoma. Immunohistochemistry of
      the tumor cells revealed diffuse immunoreactivity for estrogen receptors,
      progesterone receptors, vimentin, and CD34. The stains for cytokeratin,
      epithelial membrane antigen, desmin, smooth muscle alpha-actin, muscle-specific
      actin, and S-100 were negative. These results were mostly consistent with those
      of previous reports and suggest that the tumors cells were derived from primitive
      mesenchymal cells which occur normally in this lesion and which show the
      potential for diverse lines of myoid differentiation.

PMID- 11975688
TI  - Type III radical hysterectomy induction chemotherapy for patients with locally
      advanced cervical carcinoma.

PMID- 11975690
TI  - Application of dynamic laser scattering to the quality control of injectable
      drugs: polymer formation in ampicillin solution.
AB  - OBJECTIVE: To assess the usefulness of dynamic laser scattering for monitoring
      the stability of ampicillin after reconstitution from commercially available
      vials with respect to the polymer formation and potency. METHODS: Polymer
      formation and the remaining potency of the reconstituted ampicillin solution were
      estimated using dynamic laser scattering and high-performance liquid
      chromatography. RESULTS: The laser light-scattering submicron particle analyser
      was sufficiently sensitive for detecting both monomer and polymer aggregates with
      the average diameter of 1.1 +/- 0.2 and 7.3 +/- 1.7 nm, respectively, in the
      ampicillin solution. Polymer formation was dependent on both the storage
      temperature and the storage period, but it was detected, even when no
      precipitates were visible and when loss of potency was less than 10% of the
      initial value following storage at 4 or -15 degrees C. CONCLUSION: Submicron
      particle analysis using scanning electron microscopy, when used in combination
      with high-performance liquid chromatography, provides a useful method for
      studying polymer formation in antibiotic solutions and for the quality control of
      antibiotic injections during storage.

PMID- 11975691
TI  - Heart rate variability--a therapeutic target?
AB  - Reduced heart rate variability (HRV) is a powerful and independent predictor of
      an adverse prognosis in patients with heart disease and in the general
      population. The HRV is largely determined by vagally mediated beat to beat
      variability, conventionally known as respiratory sinus arrhythmia. Thus, HRV is
      primarily an indicator of cardiac vagal control. It is still unclear whether the
      relationship between measures of cardiac vagal control and mortality is causative
      or mere association. Possible mechanisms by which cardiac vagal activity might
      beneficially influence prognosis include a decrease in myocardial oxygen demand,
      a reduction in sympathetic activity and a decreased susceptibility of the
      ventricular myocardium to lethal arrhythmia. In animals, augmentation of cardiac
      vagal control by nerve stimulation or by drugs is associated with a reduction in
      sudden death in susceptible models. In humans a number of drugs which have been
      shown to reduce mortality and sudden death in large randomised trials can also be
      demonstrated to increase HRV. As a result of this evidence, it has been suggested
      that the effect of drugs or other therapeutic manoeuvres on HRV might be used to
      predict clinical efficacy. The use of HRV as a therapeutic target is discussed in
      this review.

PMID- 11975692
TI  - Use of night-time benzodiazepines in an elderly inpatient population.
AB  - AIM: To examine benzodiazepine prescribing for sleep induction in an elderly
      medical inpatient population to determine if hospital prescribing may have
      encouraged benzodiazepine use following discharge. Secondary objectives included
      assessment of quality of sleep in hospital compared with home and monitoring for
      possible benzodiazepine side-effects. METHOD: Inpatient and discharge prescribing
      of benzodiazepines used for sleep induction were recorded in two medical wards
      over a 3-month period. A questionnaire was used to obtain information on
      patients' sleep patterns at home and in hospital. A follow-up telephone survey at
      2-3 weeks post-discharge was made for those patients who were prescribed
      benzodiazepine at discharge. RESULTS: Benzodiazepines were prescribed for 20% of
      patients with 94% of prescriptions being for temazepam. Of the 54 patients
      prescribed benzodiazepines during admission, 57% were not taking a benzodiazepine
      at home prior to their hospital admission. At discharge, 14 patients were
      prescribed benzodiazepines for home use, eight of whom had not used them at home
      previously. On follow-up none of these eight patients expressed a desire to
      continue benzodiazepine use for sleep induction. There was a significant (P <
      0.05) reduction in sleep onset latency and number of nocturnal awakenings in
      hospital when compared with home. There was no change in sleep duration and
      overall quality of sleep. There was an association between early morning insomnia
      and benzodiazepine use. CONCLUSION: Discharge prescribing of benzodiazepines was
      appropriately limited to temazepam and did not encourage home use in previous non
      users. Benzodiazepines (primarily temazepam) were effective in the short term for
      inducing sleep in the hospital setting, with little evidence of side-effects.

PMID- 11975693
TI  - Differential tramadol and O-desmethyl metabolite levels in brain vs. plasma of
      mice and rats administered tramadol hydrochloride orally.
AB  - OBJECTIVE: To investigate a possible differential brain uptake of tramadol vs.
      its major metabolite (O-desmethyl tramadol; M1) in mice and rats. METHODS: An
      extraction and measurement technique (gas chromatograph equipped with a nitrogen
      phosphorus detector) was used to measure plasma and brain levels of tramadol and
      M1 at intervals 10-300 min after oral dosing of tramadol hydrochloride to mice
      and rats. RESULTS: For all doses of tramadol administered (5, 10, 20, or 40
      mg/kg), tramadol and M1 plasma levels were greatest 10 min after dosing: in mice,
      peak tramadol plasma levels were 47.75-736.72 ng/mL and peak M1 levels were 75.30
      1084.92 ng/mL; in rats, peak tramadol plasma levels were 185.03-455.81 ng/mL and
      peak M1 levels were 106.74-455.70 ng/mL. Tramadol brain levels were also greatest
      10 min after dosing. In mice, peak tramadol brain levels were 226.42-1847.46
      ng/g. Peak M1 levels (72.17-572.97 ng/g) occurred 20-60 min after dosing. In
      rats, peak tramadol brain levels were 258.50-1777.37 ng/g and peak M1 levels were
      80.35-289.60 ng/g. In mice, the ratio of tramadol/M1 in plasma was 0.5-1.0
      throughout the measurements, whereas the ratio in brain was about 10 at 10 min
      and about 2 from 20 to 50 min. In rats, the ratio of tramadol/M1 in plasma was
      0.5-1.5, whereas the ratio in brain was about 15 at 10 min and about 4-7
      thereafter. CONCLUSION: In mice and rats, there appears to be preferential brain
      vs. plasma distribution of tramadol over M1.

PMID- 11975694
TI  - Laxative prescribing in relation to opioid use and the influence of pharmacy
      based intervention.
AB  - INTRODUCTION: Opioid-induced constipation is a common problem and can cause
      serious complications. It is widely advised that laxatives should be started
      concurrently with opiates, unless there is a clear indication not to do so.
      OBJECTIVE: This study was undertaken to estimate how often laxatives were started
      concurrently with opiates and to describe the effect of pharmacy-based
      interventions to promote the use of laxatives in patients starting opioids.
      METHODS: Twenty-six community pharmacies identified all patients who received a
      first prescription for a strong opioid during January and February of 1998, 1999
      or 2000. Pharmacists collected information on patient, drug and prescriber
      characteristics (age, gender, use of opiates and laxatives). A separate
      questionnaire was used to collect data on pharmacy-based interventions to promote
      the simultaneous prescribing of laxatives with the opiates. RESULTS: Overall, 37%
      of the patients receiving an opioid started taking laxatives within 5 days. The
      percentage of patients who received laxatives simultaneously with opioids
      increased from 31% in 1998 to 35% in 1999 and 42% in 2000. In 117 (43%) of the
      opioid prescriptions, pharmacy-based intervention had taken place before the
      prescription date. Of these, 48.7% was accompanied by a laxative. Opioid
      prescriptions (n=152) without a pharmacy based intervention were accompanied in
      27.6%. After adjustment for covariates (including time trends), pharmacy-based
      intervention increased the probability of concomitant laxative use 1.9 [95% CI
      1.1-3.3] times. DISCUSSION: This study shows that the widely used guideline to
      start a laxative when prescribing an opioid is not always followed in daily
      practice. In addition, we showed that pharmacy-based intervention contributed to
      increasing laxative use in patients receiving opioids.

PMID- 11975695
TI  - Nomogram for individualizing supplementary iron doses during erythropoietin
      therapy in haemodialysis patients.
AB  - AIMS: An adequate iron supplement is crucial not only for prompt erythropoiesis
      but also for the restoration of tissue iron reserves in haemodialysis patients
      receiving recombinant human erythropoietin (r-HuEPO). An attempt was made to
      establish a comprehensive nomogram that allows individualization of intravenous
      (i.v.) iron doses according to patients' body weights, the initial status of
      tissue iron reserves and desired increases in haemoglobin levels. MATERIALS AND
      METHODS: Clinical and laboratory data retrieved from 95 haemodialysis patients
      who received r-HuEPO with or without iron supplements for at least 12 weeks were
      used to construct the nomogram. It was assumed that the administered iron was
      either incorporated into newly synthesized haemoglobin and tissue iron reserves
      or eliminated from the body at a constant rate. Tissue iron reserves of the
      patients were estimated by serum ferritin levels using van Wyck's equation
      (Kidney Int., 1989, 35, 712). The rate of iron loss in the patients was estimated
      by the data obtained from 15 of the above patients who exhibited stable
      haemoglobin levels but decreases in serum ferritin levels with no iron
      supplements. The validity of the equation was ascertained by comparing the
      measured serum ferritin levels at the end of r-HuEPO therapy and those predicted
      by the nomogram. The proposed nomogram was then validated prospectively in 24
      haemodialysis patients to determine whether the nomogram-recommended iron doses
      would increase both haemoglobin and serum ferritin levels within 12 weeks.
      RESULTS: The mean (+/-SD) iron loss of haemodialysis patients was calculated to
      be 10.5 +/- 7.4 mg/week. There was a significant correlation (r=0.77, P < 0.001)
      between the measured serum ferritin levels, an index of tissue iron reserves, at
      the end of r-HuEPO therapy and those predicted by the equations used for
      formulating the nomogram. The prospective study indicated that the nomogram
      recommended supplementary iron doses attained haemoglobin and serum ferritin
      levels of > 95 g/L and >100 microg/L in 79 and 50% of the patients, respectively,
      within 12 weeks. CONCLUSION: The present nomogram may be useful for
      individualizing supplementary i.v. iron doses for haemodialysis patients
      undergoing r-HuEPO therapy.

PMID- 11975696
TI  - Relationship of serum ACE inhibition to oral dose of enalapril in normotensive
      volunteers.
AB  - OBJECTIVES: To determine the relationship between oral dose of enalapril and
      parameters describing serum angiotensin converting enzyme (ACE) inhibition.
      METHODS: Four different oral doses of enalapril maleate (2.5, 5, 10 and 20 mg)
      were administered to six healthy normotensive volunteers, in a four-period
      crossover study. Serum ACE inhibition profiles were determined in each case using
      a synthetic substrate, hippuryl-histidyl-leucine (HHL). Pharmacodynamic
      parameters of the drug (Emax and AUEC0-->24) were calculated and their
      relationship to oral doses investigated using linear regression analysis.
      RESULTS: There was no significant relationship between drug dose and the two
      pharmacodynamic parameters (Emax and AUEC0-->24). The r2 values were 0.548
      (F=3.63, P=0.153) and 0.6360 (F=5.24, P=0.106) for Emax and AUEC0-->24,
      respectively. CONCLUSION: The extent of serum ACE inhibition, as the main
      determinant of the blood pressure lowering effect of enalapril, is not dose
      dependent within the single dose range of 2.5-20 mg.

PMID- 11975697
TI  - Cost analysis of fentanyl and remifentanil in coronary artery bypass graft
      surgery without cardiopulmonary bypass.
AB  - BACKGROUND: Opiates such as remifentanil have the potential to reduce time to
      extubation (TTE), shorten length of stay (LOS) and lower hospital costs, because
      of a short duration of action. However, the cost of remifentanil is approximately
      ten times higher than longer-acting opiates like fentanyl. OBJECTIVES: The
      objective of this analysis was to compare TTE, LOS and total hospital costs
      between patients who received remifentanil and fentanyl during off-pump bypass
      surgery. METHODS: The study was prospective and observational in design.
      Consecutive patients who underwent off-pump cardiac bypass surgery and received
      either remifentanil or fentanyl from September 1998 to August 1999 were screened
      for study entry. Patient bills and charges were converted to costs using hospital
      cost-to-charge ratios. The percent of patients' extubated in the operating room
      (OR), LOS and hospital costs were compared between the groups. RESULTS: The
      baseline demographics (age: 66 +/- 12 years mean +/- SD; female 36%) and
      intraoperative variables were similar between the remifentanil (n=39) and
      fentanyl (n=20) groups. Patients given remifentanil during surgery were
      significantly more likely to be extubated in the OR than patients given fentanyl
      (15 vs. 64%; P < 0.001). Mean LOS was similar in both groups (7.3 +/- 3.1 vs. 8.3
      +/- 2.7 days; P=0.27). Patients who received remifentanil incurred lower
      pulmonary function testing ($0 +/- 0 vs. $34 +/- 103; P=0.045), recovery room
      ($31 +/- 40 vs. $65 +/- 33; P=0.002) and lower ward costs ($3973 +/- 1719 vs.
      $4808 +/- 1794; P=0.09) than patients who received fentanyl. Anesthesia costs
      were higher among patients who received remifentanil ($476 +/- 102 vs. $416 +/-
      130; P=0.06). Medical and surgical supplies, OR, intensive care unit, laboratory,
      respiratory therapy, pharmacy, radiology and transfusion costs were similar
      between the two groups. The total cost was $15 272 +/- 5556 and $15 616 +/- 4169
      in the remifentanil and fentanyl groups, respectively (P=0.81). CONCLUSION:
      Remifentanil, when used in off-pump bypass surgery, is associated with an
      increased likelihood of extubation in the OR. However, LOS and total hospital
      costs remain unchanged.

PMID- 11975698
TI  - Experience with use of recombinant activated factor VII.
AB  - Recombinant activated factor VII (rFVIIa) has recently been introduced for
      improving haemostasis in haemophiliac patients developing alloantibodies
      (inhibitors) to factor VIII (FVIII) or factor IX (FIX). We describe the
      successful management of haemorrhagia with rFVIIa in five different situations:
      an episode of surgical bleeding in a patient with haemophilia A and non-surgical
      haemorrhages in four patients with haemophilia A, acquired haemophilia,
      congenital severe FV defect and pseudo-acquired haemophilia, respectively. In
      each case, rFVIIa was effective and safe. There is no doubt that rFVIIa is useful
      in the therapeutic management of patients with antibodies to FVIII or FIX.
      However, the treatment is expensive and a cost-effectiveness analysis would be
      useful.

PMID- 11975699
TI  - Leaching of diethylhexyl phthalate from polyvinyl chloride bags into intravenous
      etoposide solution.
AB  - OBJECTIVE: To compare the release of diethylhexyl phthalate (DEHP) from polyvinyl
      chloride (PVC) bags from four different manufacturers into intravenous etoposide
      solutions. METHOD: Etoposide solutions, 0.4 mg/mL, containing the vehicle
      polysorbate 80 were prepared in 5% dextrose or 0.9% sodium chloride injection PVC
      bags and stored at room temperature for 24 h. DEHP content was analysed by high
      performance liquid chromatography. RESULTS: Substantial amounts of DEHP (up to 20
      microg/mL at room temperature) leached into the etoposide solutions. However, no
      significant differences were found in the amounts of DEHP leached into the
      etoposide infusion solutions prepared using either 5% dextrose or 0.9% sodium
      chloride injection and stored in the four different containers. CONCLUSION: To
      minimize patient exposure o DEHP, etoposide solutions should ideally be stored in
      a glass or polyolefin container.

PMID- 11975700
TI  - Penetration of levofloxacin into skin tissue after oral administration of
      multiple 750 mg once-daily doses.
AB  - OBJECTIVE: To probe the pharmacokinetic basis for the use of levofloxacin for
      complicated skin and skin-structure infections (SSSIs) at a once-daily dosage of
      750 mg by investigating its penetration into skin tissue. METHOD: Ten healthy
      volunteers were administered three oral, once-daily 750 mg doses of levofloxacin,
      and levofloxacin concentrations were subsequently measured over time (0.5-24 h)
      in skin-punch biopsy tissue and plasma. RESULTS: Skin tissue concentrations
      consistently exceeded those in plasma at every time point, with tissue/plasma
      ratios of 1.37 +/- 0.81 for peak concentration and 1.97 +/- 0.35 for area under
      the concentration versus time curve. Three of the ten subjects reported treatment
      emergent adverse events (AEs) that were considered unrelated to treatment. An
      11th subject who had enrolled in the study withdrew after AEs of mild severity
      that were possibly related to the study drug. CONCLUSION: The results support the
      clinical usage of levofloxacin 750 mg once-daily for complicated SSSIs.

PMID- 11975701
TI  - The contribution of cohort studies to prescribing research.
AB  - This paper highlights the main issues in the design, analysis and interpretation
      of cohort studies used in prescribing research.

PMID- 11975702
TI  - Noninvasive molecular tracking of colonizing wolf (Canis lupus) packs in the
      western Italian Alps.
AB  - We used noninvasive methods to obtain genetic and demographic data on the wolf
      packs (Canis lupus), which are now recolonizing the Alps, a century after their
      eradication. DNA samples, extracted from presumed wolf scats collected in the
      western Italian Alps (Piemonte), were genotyped to determine species and sex by
      sequencing parts of the mitochondrial DNA (mtDNA) control-region and ZFX/ZFY
      genes. Individual genotypes were identified by multilocus microsatellite analyses
      using a multiple tubes polymerase chain reaction (PCR). The performance of the
      laboratory protocols was affected by the age of samples. The quality of
      excremental DNA extracts was higher in samples freshly collected on snow in
      winter than in samples that were older or collected during summer. Preliminary
      mtDNA screening of all samples allowed species identification and was a good
      predictor of further PCR performances. Wolf, and not prey, DNA targets were
      preferentially amplified. Allelic dropout occurred more frequently than false
      alleles, but the probability of false homozygote determinations was always <
      0.001. A panel of six to nine microsatellites would allow identification of
      individual wolf genotypes, also whether related, with a probability of identity
      of < 0.015. Genealogical relationships among individuals could be determined
      reliably if the number of candidate parents was 6-8, and most of them had been
      sampled and correctly genotyped. Genetic data indicate that colonizing Alpine
      wolves originate exclusively from the Italian source population and retain a high
      proportion of its genetic diversity. Spatial and temporal locations of individual
      genotypes, and kinship analyses, suggest that two distinct packs of closely
      related wolves, plus some unrelated individuals, ranged in the study areas. This
      is in agreement with field observations.

PMID- 11975703
TI  - Comparison of genetic diversity estimates within and among populations of
      maritime pine using chloroplast simple-sequence repeat and amplified fragment
      length polymorphism data.
AB  - We compared the genetic variation of Pinus pinaster populations using amplified
      fragment length polymorphism (AFLP) and chloroplast simple-sequence repeat
      (cpSSR) loci. Populations' levels of diversity within groups were found to be
      similar with AFLPs, but not with cpSSRs. The high interlocus variance associated
      with the AFLP loci could account for the lack of differences in the former.
      Although AFLPs revealed much lower genetic diversity than cpSSRs, the levels of
      among-population differentiation found with the two types of marker were similar,
      provided that loci showing fewer than four null-homozygotes, in any population,
      were pruned from the AFLP data. Moreover, the French and Portuguese populations
      were clearly differentiated from each other, with both markers. The Mantel test
      showed that the genetic distance matrix calculated using the AFLP data was
      correlated with the matrix derived from the cpSSRs. Because of the concordance
      found between markers we conclude that gene flow was indeed the predominant force
      shaping nuclear and chloroplastic genetic variation of the populations within
      regions, at the geographical scale studied.

PMID- 11975704
TI  - Fine-scale population structure and dispersal in Biomphalaria glabrata, the
      intermediate snail host of Schistosoma mansoni, in Venezuela.
AB  - Biomphalaria glabrata is the main intermediate host of Schistosoma mansoni in
      America and one of the most intensely studied species of freshwater snails, yet
      very little is known about its population biology. Here, we used seven highly
      polymorphic microsatellite loci to analyse genetic diversity in the Valencia lake
      basin, which represents the core of the endemic area for schistosomiasis in
      Venezuela. Populations were sampled at short spatial scale (a few kilometres),
      both inside the lake and in ponds or rivers near the lake. Our results indicate
      that B. glabrata essentially cross-fertilizes, with little variation in selfing
      rates among populations. Our markers detected considerable genetic variation,
      with an average heterozygosity of 0.60. More diversity per population was found
      within than outside the lake, suggesting an influence of connectivity among
      populations on the levels of genetic diversity. A marked population structure was
      detected and lake populations were less structured than other populations. Most
      individuals were assigned to their population of origin using an assignment test.
      No strong demographic signal (e.g. bottleneck) was detected, though lake
      populations are likely to experience bottlenecks more frequently than the other
      populations analysed. Differences in gene flow therefore seem to play an
      important role in population differentiation and in the restoring of genetic
      diversity in demographically unstable populations.

PMID- 11975705
TI  - The Mediterranean fruit fly in California: evidence for multiple introductions
      and persistent populations based on microsatellite and mitochondrial DNA
      variability.
AB  - Microsatellite and mitochondrial DNA (mtDNA) variability data were used to study
      outbreaks of Mediterranean fruit fly in California in the years 1992-94 and 1997
      99. A total of 359 flies caught in monitoring traps during these years were
      examined at three polymorphic mtDNA restriction sites and two microsatellite
      loci. Composite genotypes obtained through analysis of these markers indicate at
      least five independent introductions of medflies into California between 1992 and
      1998. Whereas the majority of specimens displayed a single mtDNA haplotype (AAA),
      variation of microsatellite alleles among these flies suggests at least one
      additional introduction in 1993 into southern California. Flies displaying the
      AAB haplotype sampled in 1992 both in northern and southern California shared
      microsatellite alleles absent in AAA flies although lacking others commonly found
      in AAA specimens, thus supporting the hypothesis of an independent introduction
      of these flies from a different source. In contrast to earlier infestations, a
      few specimens caught in southern California in 1993 and again in 1998 showed both
      mtDNA and microsatellite patterns consistent with a Hawaiian origin. Single flies
      collected in Santa Clara County in 1997 and in El Monte, Los Angeles County & in
      1999 most likely represent a sixth and seventh distinct introduction,
      respectively.

PMID- 11975706
TI  - Population history of Manihot esculenta (Euphorbiaceae) inferred from nuclear DNA
      sequences.
AB  - The nature of gene flow in plants -- including the propensity for interspecific
      introgression -- makes them interesting candidates for phylogeographical
      analysis. Plant phylogeography studies have been limited, however, by the
      availability of suitable intraspecific variation. In this study, DNA sequence
      variation from a nuclear gene [Glyceraldehyde 3-phosphate dehydrogenase; (G3pdh)]
      was used to examine the population history of Manihot esculenta ssp.
      flabellifolia and a potentially hybridizing species, M. pruinosa. These species
      occur in the rainforest-savanna ecotone adjoining the Amazon basin, a region
      believed to have undergone major habitat shifts since the Pleistocene.
      Geographical distributions of the G3pdh haplotypes indicate genetic isolation-by
      distance across the range of M. esculenta ssp. flabellifolia. However, there is
      greater genetic similarity between northeastern and western populations than
      would be expected given the present species distribution. A nested clade analysis
      suggests that northeastern and western populations were connected by gene flow
      until relatively recently, when they became fragmented. This inferred
      fragmentation event is consistent with post-Pleistocene habitat shifts proposed
      for the Amazon basin. At the interspecific level, haplotype sharing with M.
      pruinosa may reflect either recent interspecific introgression or incomplete
      lineage sorting between these closely related species.

PMID- 11975707
TI  - Molecular analysis of an 11,700-year-old rodent midden from the Atacama Desert,
      Chile.
AB  - DNA was extracted from an 11,700-year-old rodent midden from the Atacama Desert,
      Chile and the chloroplast and animal mitochondrial DNA (mtDNA) gene sequences
      were analysed to investigate the floral environment surrounding the midden, and
      the identity of the midden agent. The plant sequences, together with the
      macroscopic identifications, suggest the presence of 13 plant families and three
      orders that no longer exist today at the midden locality, and thus point to a
      much more diverse and humid climate 11,700 years ago. The mtDNA sequences suggest
      the presence of at least four different vertebrates, which have been putatively
      identified as a camelid (vicuna), two rodents (Phyllotis and Abrocoma), and a
      cardinal bird (Passeriformes). To identify the midden agent, DNA was extracted
      from pooled faecal pellets, three small overlapping fragments of the
      mitochondrial cytochrome b gene were amplified and multiple clones were
      sequenced. These results were analysed along with complete cytochrome b sequences
      for several modern Phyllotis species to place the midden sequence
      phylogenetically. The results identified the midden agent as belonging to an
      ancestral P. limatus. Today, P. limatus is not found at the midden locality but
      it can be found 100 km to the north, indicating at least a small range shift. The
      more extensive sampling of modern Phyllotis reinforces the suggestion that P.
      limatus is recently derived from a peripheral isolate.

PMID- 11975708
TI  - Mesobuthus gibbosus (Scorpiones: Buthidae) on the island of Rhodes --
      hybridization between Ulysses' stowaways and native scorpions?
AB  - Allozyme data suggest that the Rhodes population of Mesobuthus gibbosus is a
      hybrid population of recent origin. Namely, it is a mixture between an
      autochthonous population and an artificially introduced population probably from
      the Greek mainland. All samples were mainly composed of F1 hybrid genotypes and
      genotypes either fixed for autochthonous or introduced alleles. Back-cross hybrid
      genotypes were very rare. Mitochondrial DNA analysis, in contrast, revealed only
      one group of closely related haplotypes that are unique for the Rhodes
      populations, thus suggesting asymmetric introgression of the two marker classes.

PMID- 11975709
TI  - Mitochondrial DNA variation along an altitudinal gradient in the greater white
      toothed shrew, Crocidura russula.
AB  - The distribution of mitochondrial control region-sequence polymorphism was
      investigated in 15 populations of Crocidura russula along an altitudinal gradient
      in western Switzerland. High-altitude populations are smaller, sparser and appear
      to undergo frequent bottlenecks. Accordingly, they showed a loss of rare
      haplotypes, but unexpectedly, were less differentiated than lowland populations.
      Furthermore, the major haplotypes segregated significantly with altitude. The
      results were inconsistent with a simple model of drift and dispersal. They
      suggested instead a role for historical patterns of colonization, or,
      alternatively, present-day selective forces acting on one of the mitochondrial
      genes involved in metabolic pathways.

PMID- 11975710
TI  - Single nucleotide polymorphisms derived from ancestral populations show no
      evidence for biased diversity estimates in Drosophila melanogaster.
AB  - Single nucleotide polymorphisms (SNPs) are about to become one of the most
      popular genetic markers for genetic model organisms. To test the usefulness of
      SNPs for estimating genetic diversity, we surveyed three genomic regions in two
      Drosophila melanogaster populations, one from Africa and one European, collected
      in Austria. Diversity estimates based on the full SNP set indicated higher levels
      of variability in the African than in the European flies. When the analysis was
      based on the European SNP set, European and African flies had similar levels of
      variability. Interestingly, this bias was not observed for diversity estimates
      using SNPs derived from the ancestral African population. This result suggests
      that diversity estimates based on SNPs from ancestral populations could provide a
      general strategy to avoid biased SNP diversity estimates. Finally, the potential
      of SNPs for nonmodel organisms is discussed.

PMID- 11975711
TI  - Structural and mechanical remodelling of the common bile duct after obstruction.
AB  - Biliary obstruction in man, most often caused by cholelithiasis, induces
      remodelling of the bile ducts. Obstruction-induced structural remodelling of the
      common bile duct (CBD) has been previously described. The mechanical changes that
      accompany the structural remodelling, however, have not been studied in detail.
      The aim of this study is to quantify the structural and mechanical changes in the
      CBD at different time intervals after acute obstruction. The CBD was ligated in
      the pig, near the duodenum, and studied after 3 h, 12 h, 2 days, 8 days and 32
      days (n=5 in each group). One additional animal in each group was sham-operated.
      At each scheduled time, the CBD was mechanically tested in vitro with a computer
      controlled volume infusion system to study the pressure-volume relationship of
      the CBD segment. A video camera provided simultaneous measurements of the outer
      dimensions of the CBD at the various pressures. The diameter and wall thickness
      of the CBD increased about three-fold in the 32-day group compared to the sham
      group (P < 0.001). The circumferential stress-strain relationship differed
      between groups (P < 0.001); it was shifted to the right, indicating softening, in
      the 3-h, 12-h, and 2-day groups and to the left, indicating stiffening, in the 8
      day and 32-day group, compared to the sham group. The longitudinal stress-strain
      curves were all shifted to the left of the circumferential stress-strain curves
      (P < 0.05). The collagen area increased during obstruction (P < 0.001) but no
      correlation between the size of the collagen area and the biomechanical
      parameters was found. A practical implication of the present study serves as a
      warning to surgeons. A reduction in the wall stiffness in the first several days
      of obstruction along with an increased duct diameter and a decreased wall
      thickness suggest that operative procedures such as suturing, anastomosis and
      procedures related to ERCP must be performed with special care to avoid damage to
      the CBD.

PMID- 11975712
TI  - Effects of pramlintide, an amylin analogue, on gastric emptying in type 1 and 2
      diabetes mellitus.
AB  - Pramlintide delays gastric emptying, possibly by a centrally mediated mechanism.
      Our aim was to determine whether the effects of pramlintide on gastric emptying
      differ in people with type 1 or type 2 diabetes who had no history of
      complications. Using a randomized, three-period, two-dose, crossover design, we
      studied the effects of 0, 30, or 60 microg t.i.d. pramlintide subcutaneously for
      5 days each in six type 1 and six type 2 diabetic subjects. Gastric emptying of
      solids was measured by 13C-Spirulina breath test. Plasma pancreatic polypeptide
      (HPP) response to the test meal was also measured. Relative to placebo [t 50% 91
      +/- 6 min (means +/- SEM)], pramlintide equally delayed gastric emptying
      following 30 or 60 microg t.i.d. (268 +/- 37 min, 329 +/- 49 min, respectively; P
      < 0.01]. Postprandial HPP levels were lower in response to 30 and 60 microg
      pramlintide compared to placebo. There were no significant differences in the
      effects on gastric emptying or HPP levels between type 1 and type 2 diabetic
      subjects. Pramlintide delays gastric emptying in diabetes unassociated with
      clinically detected complications. Further studies are needed in diabetic
      patients with impaired gastric motor function.

PMID- 11975713
TI  - Effect of butyrate on membrane potential, ionic currents and intracellular Ca2+
      concentration in cultured rat myenteric neurones.
AB  - Myenteric neurones from 1-10-day-old rats were isolated from the small and large
      intestine by enzymatic digestion with collagenase. Single cells were collected
      and kept in culture for up to 1 week. After 1-5 days in culture, membrane
      potential and ionic currents were measured with the whole-cell patch-clamp
      technique. The intracellular Ca2+ concentration was measured with the fura-2
      method. The short-chain fatty acid butyrate (50 mmol L-1) induced a reversible
      hyperpolarization of the myenteric neurones by about 10 mV. This
      hyperpolarization was concomitant with an inhibition of a TTX-sensitive Na+
      current. The hyperpolarization could be suppressed by intracellular application
      of Cs+, a nonselective K+ channel blocker. Fura-2 experiments revealed that
      butyrate induced an increase of the intracellular Ca2+ concentration. The
      butyrate response was suppressed by thapsigargin, indicating that butyrate
      stimulates the release of intracellular Ca2+. This release is responsible for the
      voltage response, because intracellular chelation of Ca2+ inhibited the butyrate
      induced hyperpolarization. Consequently, butyrate acts on enteric neurones by
      releasing Ca2+ from intracellular stores with the consequence of the activation
      of K+ channels, followed by a hyperpolarization.

PMID- 11975714
TI  - The role of remote gut inflammation in duodenojejunal dysmotility.
AB  - The aim of this prospective study was to determine the role of remote
      inflammation of the gut on duodenojejunal motor status by comparing patients with
      acute cholecystitis (AC) to those with biliary colic (BC). Thirty-six gallstone
      patients (11 AC and 25 BC) were explored. Manometric recordings were performed
      during fasting and after a 750-kcal meal and ended by an intravenous injection of
      100 mg trimebutine. Patient data were compared to those of 20 healthy controls.
      Phases III were more frequently absent in AC patients than in BC patients (P <
      0.01) and controls (P < 0.05). When phase III characteristics were similar
      between the AC and BC group, the phase III amplitude was lower in both groups
      than in controls (P < 0.0001). After the meal, the mean motor index in the
      jejunum expressed by the area under the curve (AUC) per 30-min period was higher
      in the AC group than in BC group and controls (P < 0.05). Specific motor
      phenomena were observed after the meal. In particular, propagating clusters of
      contractions (PCCs) were more frequent in AC patients than in BC (P < 0.05) and
      controls (P < 0.01). A lack of the expected decrease in the AUC during recording
      occurred with the same frequency in the AC and BC groups but was more frequent in
      patients than in controls (P < 0.05). In 8/11 patients in the AC group with
      duodenojejunal tracings before and 3 months after surgery, preoperative motor
      disturbances disappeared in 5/8 patients and improved in 3/8 patients. The higher
      frequency of duodenojejunal motor disturbances especially after a meal in
      patients with AC and their disappearance in most of the patients after removal of
      the infected gallbladder suggest that remote inflammation of the gut affects
      duodenojejunal motility.

PMID- 11975715
TI  - Effects of motilin on human interdigestive gastrointestinal and gallbladder
      motility, and involvement of 5HT3 receptors.
AB  - A plasma motilin peak and a partial gallbladder emptying precede the antral phase
      III of the migrating motor complex (MMC). To clarify the causal relationship
      between these factors, we aimed to study the role of motilin in interdigestive
      gastrointestinal and gallbladder motility simultaneously. In addition,
      involvement of 5HT3 receptors in the action of motilin was studied. Eight
      fasting, healthy male volunteers received 13Leu-motilin or 0.9% NaCl i.v. for 30
      min, in randomized order on two separate occasions, from 30 min after phase III.
      Seven of the eight subjects also received the 5HT3 receptor antagonist
      ondansetron in addition to motilin, on a third occasion. Antroduodenal motility,
      gallbladder volumes and plasma motilin were measured. The interval between the
      start of infusion and phase III was 95.0 (57.6-155.7) min for saline, 28.7 (21.0
      33.2) min for motilin, and 39.3 (30.7-100.5) min for motilin + ondansetron (P <
      0.05). Gallbladder volume decreased by one-third from 10 min after both motilin
      and motilin + ondansetron infusion (P < 0.05), and returned to baseline with
      duodenal passage of phase III. In two of the seven subjects phase III was absent
      after motilin + ondansetron, although gallbladder volume decreased and only
      refilled during a later spontaneous phase III. We conclude that motilin induces
      both partial gallbladder emptying and antral phase III. Indeed, although
      gallbladder emptying clearly precedes antral phase III, ondansetron only
      prevented phase III in some cases and had no effect on gallbladder emptying.
      Passage of phase III in the duodenum makes an important contribution to
      gallbladder refilling.

PMID- 11975716
TI  - Ca2+ involvement in the action potential generation of myenteric neurones in the
      rat oesophagus.
AB  - Intracellular recordings were used to study the physiological behaviour of rat
      oesophageal myenteric neurones, which are embedded in striated muscle. Injection
      of depolarizing pulses evoked action potentials with a clear 'shoulder' in all
      neurones. This shoulder disappeared under low Ca2+/high Mg2+ conditions.
      Tetrodotoxin (TTX; 1 micromol L-1) did not impede spike firing, whereas under
      combined TTX and low Ca2+/high Mg2+ conditions the action potentials were
      completely abolished, indicating that TTX- resistant action potentials are
      mediated by a Ca2+ current. Further experiments with omega-conotoxin GVIA (100
      nmol L-1) revealed that these Ca2+ currents enter the cell via N-type voltage
      activated Ca2+ channels (see also accompanying paper). Tetraethylammonium (10
      mmol L-1) caused broadening of the action potentials, which probably resulted
      from prolonged Ca2+ influx due to blockade of the delayed rectifier K+ channel.
      Although Ca2+ appears to be involved in the spike generation of all rat
      oesophageal myenteric neurones, only a minority (14%) shows a slow
      afterhyperpolarization. Thus, no strict correlation exists between the presence
      of a shoulder and a slow afterhyperpolarization. Furthermore, morphological
      identification of 25 of the impaled neurones revealed that there was no strict
      correlation between morphology and electrophysiological behaviour. Consequently,
      rat oesophageal myenteric neurones appear to differ in several aspects from
      myenteric neurones in smooth muscle regions of the gastrointestinal tract.

PMID- 11975717
TI  - Immunohistochemical localization of voltage-activated calcium channels in the rat
      oesophagus.
AB  - Voltage-activated calcium channels play an important role in the physiology of
      the enteric nervous system. To determine which types of voltage-activated calcium
      channels are present in the rat oesophagus, an immunohistochemical study was
      performed using specific antibodies for the alpha1 subunits of Cav2.1 (P/Q-type),
      Cav2.2 (N-type), Cav1.2 and Cav1.3 (L-type) calcium channels. All myenteric cell
      bodies showed Cav2.2 immunoreactivity, whereas labelling for this N-type channel
      was absent in nerve fibres. Cav1.2 immunoreactivity was found on nerve fibres in
      the myenteric plexus and on fibres innervating the striated muscle of the rat
      oesophagus, whereas no labelling was detected on neuronal somata.
      Immunoreactivity against Cav1.3 was not detected in the myenteric plexus or at
      the level of the striated muscle. Labelling for Cav2.1 was absent at the level of
      the myenteric plexus, but present in the striated muscle layer at the level of
      the motor endplates. Comparison with recent literature data from rat small
      intestine reveals region-specific distribution patterns of the various subtypes
      of voltage-activated calcium channels within the enteric nervous system. In
      addition, the present immunohistochemical data corroborate our physiological data
      (see accompanying paper), which indicate that the Cav2.2 (N-type) channel is the
      predominant channel involved in the generation of the calcium-dependent action
      potential evoked by intrasomatic depolarizing current pulses in all rat
      oesophageal myenteric neurones.

PMID- 11975718
TI  - Bile flow to the duodenum is reduced in hypothyreosis and enhanced in
      hyperthyreosis.
AB  - Disturbances in sphincter of Oddi (SO) function may prevent normal bile flow and
      thus enhance probability of common bile duct stone (CBDS) formation. We have
      previously shown increased prevalence of diagnosed hypothyroidism in CBDS
      patients, which may be explained by thyroxine-induced inhibition of SO
      contractility, in addition to previously suggested changes in bile composition
      and hepatocytic excretion. The aim of this study was to investigate biliary
      dynamics in relation to altered thyroid gland function in rat, a rodent without a
      gallbladder. Euthyroid, hypothyroid or hyperthyroid Spraque-Dawley rats were
      anaesthetized with i.p. urethane, and exsanguinated at 15, 45, or 60 min after
      intravenous 99mTc HIDA injection. At these timepoints, the bile flow to intestine
      was determined by measuring the relative intestine vs. liver radioactivity. At 45
      min this was 44% lower in hypothyroid rats and at 60 min 73% higher in
      hyperthyroid rats compared to euthyroid rats, while hepatic radioactivity at 15
      min and blood pressure at injection were similar in the groups. We conclude that
      the bile flow to duodenum is reduced in hypothyreosis and enhanced in
      hyperthyreosis.

PMID- 11975720
TI  - Immunoreactivity of Hu proteins facilitates identification of myenteric neurones
      in guinea-pig small intestine.
AB  - Hu proteins, together with neurone-specific enolase (NSE), protein gene product
      9.5 (PGP-9.5), microtubule-associated protein-2 (MAP-2) and tubulin beta III
      isoform, were evaluated immunohistochemically as neuronal markers in whole-mount
      preparations and cultures obtained from the myenteric plexus of guinea-pig small
      intestine. Anti-Hu immunostaining marked the ganglion cell somas and nuclei
      without staining of the neuronal processes in the whole-mounts and cultures. The
      ganglion cell bodies were not obscured by staining of multiple neuronal fibres
      and this facilitated accurate counting of the neurones. MAP2 immunostaining also
      provided clear images of individual neurones in both whole mounts and cultures.
      Immunoreactivity for NSE, PGP-9.5 and tubulin beta III isoform provided sharp
      images of the ganglion cells in culture, but not in whole-mount preparations.
      Strong staining of the neuronal processes in the whole-mount preparations
      obscured the profiles of the ganglion cell bodies to such an extent that accurate
      counting of the total neuronal population was compromised. Anti-Hu immunostaining
      was judged to be an acceptable method for obtaining reliable estimates of total
      numbers of myenteric neurones in relation to other specific histochemical
      properties such as histamine binding.

PMID- 11975719
TI  - Physiological study of interstitial cells of Cajal identified by vital staining.
AB  - Interstitial cells of Cajal (ICC) form networks that intercalate between the
      enteric nervous system and smooth muscle cells and play a fundamental role in the
      control of gastrointestinal motility by initiating rhythmic electrical activity.
      In this report, we used a method to examine the physiological and morphological
      properties of ICC in living, intact tissues. ACK2, an anti-Kit antibody, was
      conjugated to a fluorescent probe and used to identify individual ICC for
      intracellular electrical recordings, to record changes in intracellular calcium
      concentration using fluorescent dyes and for confocal microscopy. Cyclic changes
      in intracellular calcium concentration were recorded in ICC with a frequency
      similar to the electrical slow wave. In addition, injection of a fluorescent dye
      into single ICC enabled the three-dimensional reconstruction of single myenteric
      plexus ICC within the intact network. The data show that ICC in intact networks
      from the myenteric plexus region in living tissues in the guinea-pig antrum
      exhibit an electrical slow wave, and that intracellular calcium oscillates at a
      frequency similar to the slow wave.

PMID- 11975722
TI  - Salt- and glyphosate-induced increase in glyoxalase I activity in cell lines of
      groundnut (Arachis hypogaea).
AB  - Glyoxalase I (EC 4.4.1.5) activity has long been associated with rapid cell
      proliferation, but experimental evidence is forthcoming, linking its role to
      stress tolerance as well. Proliferative callus cultures of groundnut (Arachis
      hypogaea L. cv. JL24) showed a 3.3-fold increase in glyoxalase I activity during
      the logarithmic growth phase, correlating well with the data on FW gain and
      mitotic index. Inhibition of cell division decreased glyoxalase I activity and
      vice versa, thus further corroborating its role as a cell division marker enzyme.
      Cell lines of A. hypogaea selected in the presence of high salt (NaCl) and
      herbicide (glyphosate) concentrations, yielded 4.2- to 4.5-fold and 3.9- to 4.6
      fold elevated glyoxalase I activity, respectively, in a dose dependent manner
      reflective of the level of stress tolerance. The stress-induced increase in
      enzyme activity was also accompanied by an increase in the glutathione content.
      Exogenous supplementation of glutathione could partially alleviate the growth
      inhibition of callus cultures induced by methylglyoxal and d-isoascorbic acid,
      but failed to recover the loss in glyoxalase I activity due to d-isoascorbic
      acid. The adaptive significance of elevated glyoxalase I activity in maintaining
      glutathione homeostasis has been discussed in view of our understanding on the
      role of glutathione in the integration of cellular processes with plant growth
      and development under stress conditions.

PMID- 11975721
TI  - Effects of duodenal fat, protein or mixed-nutrient infusions on epigastric
      sensations during sustained gastric distension in healthy humans.
AB  - Duodenal fat modulates sensory and motor responses to gastric distension and
      raises plasma cholecystokinin compared with glucose. The effects of protein (also
      releasing cholecystokinin), or mixed nutrients (with a balanced macronutrient
      composition), on gastrointestinal sensations in relation to gastric relaxation
      and plasma cholecystokinin concentrations are not known. The aim of this study
      was therefore to compare the effects of duodenal infusion of fat, protein or
      mixed nutrients during sustained gastric distension (mimicking the intragastric
      presence of food) on these parameters. In 10 healthy subjects, gastric distension
      to fullness was maintained for 90 min, while gastric volume, sensations and
      plasma cholecystokinin were monitored during duodenal infusion of isotonic saline
      or nutrients (2 kcal min-1). During saline infusion, all parameters remained
      unchanged for 90 min. Initially, only lipid increased plasma cholecystokinin,
      gastric volume and scores for sensations. Cholecystokinin and gastric volume
      responses to protein and mixed nutrients were delayed and not associated with
      significant changes in sensations. In conclusion, the intensity of
      gastrointestinal sensations is related to, but not entirely explained by, the
      magnitude in intragastric volume and plasma cholecystokinin changes. Our results
      offer new insights into the role of dietary nutrient composition in
      gastrointestinal sensations, and may have implications for the dietary management
      of digestive symptoms.

PMID- 11975723
TI  - Regulation of the catalytic behaviour of L-form starch phosphorylase from sweet
      potato roots by proteolysis.
AB  - Starch phosphorylase (SP) is an enzyme used for the reversible phosphorolysis of
      the alpha-glucan in plant cells. When compared to its isoform in an animal cell,
      glycogen phosphorylase, a peptide containing 78 amino acids (L78) is inserted in
      the centre of the low-affinity type starch phosphorylase (L-SP). We found that
      the amino acid sequence of L78 had several interesting features including the
      presence of a PEST region, which serves as a signal for rapid degradation.
      Indeed, most L-SP molecules isolated from mature sweet potato roots were nicked
      in the middle of a molecule, but still retained their tertiary or quaternary
      structures, as well as full catalytic activity. The nicking sites on the L78 were
      identified by amino acid sequencing of these peptides, which also enabled us to
      propose a proteolytic process for L-SP. Enzyme kinetic studies of L-SP in the
      direction of starch synthesis indicated that the Km decreased during the
      proteolytic process when starch was used as the limiting substrate, but the Km
      for the other substrate (Glc-1-P) increased. On the other hand, the maximum
      velocities (Vmax) increased for both substrates. Mobility of the nicked L-SP was
      retarded on a native polyacrylamide gel containing soluble starch, indicating the
      increased affinity for starch. Results in this study suggested that L78 and its
      proteolytic modifications might play a regulatory role on the catalytic behaviour
      of L-SP in starch biosynthesis.

PMID- 11975724
TI  - Pyrophosphate import and synthesis by plant mitochondria.
AB  - The matrix level of pyrophosphate (PPi) in mitochondria isolated from etiolated
      pea (Pisum sativum L. cv. Alaska) stems was evaluated, on the basis of an
      enzymatic assay, to be approx. 0.2 mM. Pyrophosphate could enter from the
      cytoplasm to the mitochondria via adenine nucleotide translocase (ANT), because F
      and Ca2+ (two penetrating PPiase inhibitors) and atractylate (ANT inhibitor)
      inhibited PPiase activity in isolated mitochondria supplied with PPi. This result
      was also confirmed by measuring oxygen consumption and membrane potential
      (DeltaPsi) in succinate-energized mitochondria. In a medium free of phosphate
      (Pi), the addition of PPi before the substrate rendered possible an ADP
      stimulated oxygen consumption that was inhibited by F- or Ca2+. In a similar
      experiment, ADP induced the dissipation of DeltaPsi when it was added after the
      succinate-generated DeltaPsi had reached a steady state and, again, F- inhibited
      this dissipation. These results imply that PPi enters the mitochondria where it
      is hydrolyzed to 2 Pi which become available for the H+-ATPase (EC 3.6.1.34). In
      addition, PPi may be synthesized by the H+-PPiase (EC 3.6.1.1), acting as a
      synthase. This evidence arises from the observation that Pi stimulated an oxygen
      consumption (respiratory control ratio of 1.7) that was inhibited by F- or Ca2+.
      The physiological role of the mitochondrial H+-PPiase is discussed in the light
      of the consideration that this enzyme can catalyse a readily reversible reaction.

PMID- 11975725
TI  - Imazethapyr, an inhibitor of the branched-chain amino acid biosynthesis, induces
      aerobic fermentation in pea plants.
AB  - Acetolactate synthase (ALS; EC 4.1.3.18) inhibition is the primary mechanism of
      action of imazethapyr (IM). However, the precise mechanisms that links ALS
      inhibition with plant death have not been elucidated. Supply of IM to pea (Pisum
      sativum L) plants produced an immediate cessation of growth, caused a 50%
      inhibition of the in vivo ALS activity within 1 day of treatment, and a
      remarkable accumulation (2.7-times) of free amino acids after 3 days.
      Carbohydrates (soluble and starch) were accumulated in both leaves and roots.
      Accumulation of soluble sugars in roots preceded that of starch in leaves,
      suggesting that the accumulation of carbohydrates in leaves is not the reason for
      the arrested root growth. A transient pyruvate accumulation was observed in
      roots, 1 day after the onset of IM supply. This was coincident with an increase
      in pyruvate decarboxylase (EC 4.1.1.1), and later increases in alcohol
      dehydrogenase (EC 1.1.1.1), lactate dehydrogenase (EC 1.1.1.27), and alanine
      amino transferase (EC 2.6.1.2) activities. This enhancement of fermentative
      activities was coincident with a slight decrease in aerobic respiration. The
      overall data suggest that the impairment of ALS activity may lead to a
      fermentative metabolism that may be involved in growth inhibition and plant
      death.

PMID- 11975726
TI  - Maize replicative alpha-type DNA polymerase: separation of polymerase and primase
      activities and recognition of primase subunits.
AB  - DNA polymerase and DNA primase activities in the maize alpha-type DNA polymerase
      2 were dissociated and DNA polymerase-free DNA primase was studied. DNA primase
      synthesized primers that were 8-34 nucleotides long, with more intense bands at
      15-17 nucleotides in length. DNA polymerase 1 (a putative delta-type enzyme) or
      DNA polymerase 2 were assayed after template-priming with purified DNA primase
      and showed a differential use of templates: whereas DNA polymerase 2 used a
      polydT template more efficiently than a natural template, DNA polymerase 1 used
      both of them poorly. The molecular size of DNA primase was estimated to be 68 kDa
      by gel filtration, western blotting and by a DNA primase 'trapping' assay.

PMID- 11975727
TI  - Solubilization of galactosyltransferase that synthesizes 1,4-beta-galactan side
      chains in pectic rhamnogalacturonan I.
AB  - beta-1,4-Galactan galactosyltransferase (GT) activity was solubilized from potato
      microsomal membranes in the presence of 78 mM 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulphonic acid. The solubilized GT
      activity transferred 14[C]galactose from UDP-14[C]galactose onto the acceptor
      substrates composed of rhamnogalacturonan (RG) with short galactan chains (RG-A,
      approximately 1.2 MDa, mol% Gal/Rha = 0.7; RG-B, approximately 21 kDa, mol%
      Gal/Rha = 1.2). However, shorter RG containing short galactan chains
      (approximately 2 kDa and 1.2 kDa), RG oligomers without galactosyl-residues,
      galactan, and galactooligomers did not act as acceptor-substrates. Optimal pH for
      14[C] incorporation onto RG-A and RG-B was around 5.6 and 7.5, respectively. The
      14[C]-labelled products synthesized upon RG-A and RG-B could be digested with a
      RG specific lyase into smaller RG fragments. 1,4-beta-Endogalactanase could not
      digest the former product, whereas the latter product was digested to
      14[C]galactobiose and 14[C]galactose. This demonstrates that at least two GT
      activities were solubilized from potato microsomal membranes. One had optimal pH
      around 5.6 to transfer galactosyl residues onto RG-A, whereas the other had
      optimal pH around 7.5 to transfer galactosyl residues onto RG-B. Both synthesized
      galactan attached to the RG backbone of RG-A and RG-B, and the galactan
      synthesized onto the RG-B acceptor was 1,4-beta-linked.

PMID- 11975728
TI  - Induction by pathogen, salt and drought of a basic class II chitinase mRNA and
      its in situ localization in pepper (Capsicum annuum).
AB  - Northern blot and in situ hybridization analyses revealed that a pepper basic
      class II chitinase gene (CAChi2) is constitutively expressed in floral organs and
      root endodermis, but not in leaf, stem and fruit of pepper. Resistance of pepper
      leaves to Colletotrichum coccodes infection at a late growth stage was correlated
      with induction of beta-1,3-glucanase and PR-1 mRNA, but not of chitinase (CAChi2)
      mRNA. Transcriptional activation of the CAChi2 gene in pepper leaves occurred
      during anthracnose development. The CAChi2 transcripts were mainly localized in
      phloem cells of vascular tissues of pepper leaves infected with C. coccodes. The
      CAChi2 gene was also differentially induced in leaf and stem tissue by treatment
      with abscisic acid (ABA), sodium chloride or drought. Strong accumulation of the
      CAChi2 transcripts occurred in pepper stem tissues due to high salt and drought,
      and also due to treatment with ABA. These results suggest involvement of the
      chitinase gene in protection of pepper plants against the pathogen, but also
      document cross talk with stress signals mediated by ABA, high salinity and
      drought.

PMID- 11975729
TI  - Increased anthocyanin accumulation in aster flowers at elevated temperatures due
      to magnesium treatment.
AB  - Temperature is one of the main external factors affecting anthocyanin
      accumulation in plant tissues: low temperatures cause an increase and elevated
      temperatures cause a decrease in anthocyanin concentration. Several metals have
      been shown to increase the half-life time of anthocyanins, by forming complexes
      with them. We studied the combined effect of elevated temperatures and increased
      metal concentrations on the accumulation of anthocyanins in aster 'Sungal'
      flowers. It has been found that magnesium treatment of aster plants or detached
      flower buds, partially prevents colour fading at elevated temperatures.
      Anthocyanin concentration of aster 'Sungal' flowers grown at 29 degrees C/21
      degrees C day/night, respectively, was about half that of flowers grown at 17
      degrees C/9 degrees C. The activity of phenylalanine ammonia-lyase (PAL) and
      chalcone isomerase (CHI) decreased as the temperature increased. Treatment of
      both whole plants and detached flower buds grown at elevated temperatures in the
      presence of magnesium salts, increased flower anthocyanin concentration by up to
      80%. Measurement of magnesium following these treatments revealed an increased
      level of the metal in the petals, suggesting a direct effect. Magnesium treatment
      does not seem to cause increased synthesis of anthocyanin through a stress
      related reaction, since the activities of both PAL and CHI did not increase due
      to this treatment. The results of this study show that increasing magnesium
      levels in aster petals prevents the deleterious effect of elevated temperatures
      on anthocyanin accumulation, thus enhancing flower colour.

PMID- 11975730
TI  - Changes in superoxide dismutase activity and photosynthetic pigment content
      during growth of marine phytoplankters in batch-cultures.
AB  - The ability of phytoplankton to cope with oxidative stress is one of the main
      factors that influence its survival in the marine environment, when senescence
      conditions prevail. In a first attempt to investigate the antioxidant strategies
      of different phytoplanktonic groups face to oxidative stress, the superoxide
      dismutase (SOD; EC 1.15.1.1) activity and photosynthetic pigment content along
      the growth curves of the dinoflagellate Lingulodinium polyedrum (Stein) Dodge,
      the prasinophycean Tetraselmis gracilis (Kylin) Butcher and the diatom
      Minutocellus polymorphus (Hargraves and Guillard) Hasle, von Stosch and Syvertsen
      were evaluated in batch-cultures. Total SOD activity was determined by an
      indirect method involving the inhibition of cytochrome c reduction. The contents
      of photosynthetic pigments were analysed by HPLC using a reverse phase column (RP
      18), based on a ternary gradient. A peak of total SOD activity was detected at
      the beginning of the T. gracilis and M. polymorphus exponential growth. In L.
      polyedrum and M. polymorphus, SOD activity increased approximately three times by
      day 17 of growth, compared to the values obtained on day 3 (exponential phase) of
      the growth curve. All three species of microalgae had reduced SOD activity at the
      end of their growth. The levels of peridinin in L. polyedrum increased about 60%
      by day 17 of growth compared to the values obtained at exponential phase.
      Tetraselmis gracilis exhibited a remarkable increase (approximately 85%) in beta
      carotene concentration after 10-14 days of growth whereas the beta-carotene
      levels in M. polymorphus decreased about 85% along its growth curve. These
      findings suggest that the antioxidant response during senescence in batch
      cultures differ according to the species. Induction of SOD activity may occur
      either in the early exponential or stationary growth phases, which is important
      to prevent oxidative stress triggered by a number of factors that affects growth,
      such as nutrient and light availability.

PMID- 11975731
TI  - Expression of Oryza sativa MAP kinase gene is developmentally regulated and
      stress-responsive.
AB  - Mitogen-activated protein kinase (MAPK) pathways are modules involved in the
      transduction of extracellular signals to intracellular targets in all eukaryotes.
      In plants, there is evidence for MAPKs playing a role in the signalling of
      abiotic stresses, pathogens, plant hormones, and cell cycle cues. The large
      number and divergence of plant MAPKs indicates that this ancient mechanism of
      signal transduction is extensively used in plants. However, there have been no
      reports of classical MAPK module in rice. In this report, we have isolated a MAPK
      from rice (Oryza sativa) termed OsMAPK2. The cloned cDNA is 1457 nucleotides long
      and the deduced amino acid sequence comprised 369 amino acid residues. Sequence
      analysis revealed that the predicted amino acid sequence is 72% identical to
      tobacco wound-induced protein kinase (WIPK). Southern analysis suggested a single
      OsMAPK2 gene in rice. Analysis at the mRNA level has shown that OsMAPK2 is
      expressed in all plant organs and high relative amounts of OsMAPK2 were detected
      in the mature panicles in comparison with in the immature panicles. In suspension
      cultured cells, the OsMAPK2 mRNA transcript increased markedly upon temperature
      downshift from 26 degrees C to 4 degrees C and sucrose starvation. In contrast,
      the OsMAPK2 mRNA level rapidly declined in rice cell challenged by high
      temperature. A similarly rapid response of OsMAPK2 was observed in stress-treated
      seedlings, demonstrating that response of the MAPK pathway occurs also in intact
      plants. These results suggest that this OsMAPK2 may function in the stress
      signalling pathway as well as panicle development in rice.

PMID- 11975732
TI  - The synergistic effects of sugar and abscisic acid on myo-inositol-1-phosphate
      synthase expression.
AB  - 1L-myo-inositol-1-phosphate [Ins(1)P1] synthase (EC 5.5.1.4) catalyses the
      formation of Ins(1)P1 from glucose-6-phosphate, the first step in the
      biosynthesis of myo-inositol. Ins(1)P1 is a precursor of phytin (inositol
      hexakisphosphate), a storage form of phosphate and cations in seeds. Since
      sucrose and abscisic acid (ABA) are known to affect synthesis of storage
      compounds in seeds, we investigated the effects of ABA and sucrose on Ins(1)P1
      synthase gene (RINO1) expression in cultured cells derived from the scutellum of
      mature rice seeds. Higher levels of RINO1 transcript accumulation were evident
      after treatment with either sucrose (10-100 mM) or ABA (10-8 M to 10-4 M).
      Glucose was also effective in the upregulation, whereas mannitol was not,
      suggesting that sucrose and glucose acted as metabolizable sugars and not as
      osmotica. Treatment with ABA and sucrose together resulted in much higher levels
      of transcript accumulation, suggesting a synergistic induction of the Ins(1)P1
      synthase gene.

PMID- 11975733
TI  - Cloning of nodule-specific cDNAs of Galega orientalis.
AB  - Differential display was applied in order to clone cDNAs expressed exclusively or
      predominantly in nodules, compared to uninoculated root tissue of Galega
      orientalis. Forty-five fragments were unique for nodule RNA. These fragments were
      reamplified and cloned. Six of them produced a nodule-specific signal on Northern
      hybridization. These six fragments were sequenced. Five of the sequenced
      fragments showed homology to nodulin-gene sequences in databases, among them
      Vicia faba mRNA for protein showing partial homology with Medicago sativa nodulin
      25 (Nms25), Pisum sativum PsN466, V. faba CCP2 and CCP4, P. sativum ENOD3, and
      Maackia amurensis ENOD2. The remaining sequence had no significant homology with
      sequences in the databanks. Full-size cDNA for the homologue to V. faba mRNA for
      the protein showing partial homology with M. sativa nodulin-25 (Nms25) and P.
      sativum PsN466 were cloned and sequenced.

PMID- 11975734
TI  - Secondary xylem development in Arabidopsis: a model for wood formation.
AB  - Our understanding of the molecular controls regulating the identity of the
      vascular cambium and the development of secondary xylem and phloem have not yet
      benefited much from the use of Arabidopsis as a genetic system. Under appropriate
      growth conditions Arabidopsis undergoes extensive secondary growth in the
      hypocotyl, with the development of both a vascular and a cork cambium. The
      secondary xylem of the hypocotyl develops in two phases, an early phase in which
      only vessel elements mature and a later stage in which both vessel elements and
      fibres are found. During this second phase the secondary xylem of Arabidopsis
      closely resembles the anatomy of the wood of an angiosperm tree, and can be used
      to address basic questions about wood formation. The development of the vascular
      cambium and secondary growth in Arabidopsis hypocotyl is described and its
      utility as a model for wood formation in trees is considered.

PMID- 11975735
TI  - Age-related loss of rooting capability in Arabidopsis thaliana and its reversal
      by peptides containing the Arg-Gly-Asp (RGD) motif.
AB  - We describe here an experimental system to study the age-related decline of
      adventitious root formation in Arabidopsis thaliana L. (Heynh), ecotype Landsberg
      erecta (Ler). The system is based on the different rooting capacity of hypocotyls
      from de-rooted juvenile (12-day-old) and adult (26-day-old) plants. Hypocotyls
      from de-rooted juvenile plants rooted readily within a week of culture, and the
      rooting process was not dependent on exogenous auxin. In contrast, hypocotyls
      from de-rooted adult plants rooted poorly and only after longer periods of time.
      Exogenously applied auxin had no effect on rooting of hypocotyls from de-rooted
      adult plants. Rooting capacity, although correlated with the transition to
      flowering, did not depend on this transition. Root induction declined in a
      similar manner when the transition to flowering was delayed, either genetically
      with the fve mutant or physiologically with short days. The results showed that
      rooting of hypocotyls from de-rooted adult plants depended on the effect of
      peptides containing the RGD motif. Both the percentage of rooting and the number
      of roots were largely increased when the hypocotyls were treated transiently with
      the RGD peptide. The effect of the RGD peptide was a necessary, but not
      sufficient, condition for rooting of hypocotyls from de-rooted adult plants.

PMID- 11975736
TI  - Characterization of the developmental stages of cypress zygotic embryos by two
      dimensional electrophoresis and by cytochemistry.
AB  - Biochemical changes that characterize megagametophyte and zygotic embryo
      development in the conifer Cupressus sempervirens L. (Cupressaceae) were studied
      by complementary methods of cytochemistry and two-dimensional electrophoresis (2
      DE). These analyses revealed that early in their development megagametophytes and
      embryos were characterized by the predominant elaboration of starch in
      association with a low protein content. As their development proceeded, starch
      content gradually decreased while protein body synthesis progressively
      intensified, both in the megagametophyte and the embryo. In parallel, an increase
      in protein level as well as an accumulation of specific polypeptides could be
      observed in the two tissues. During maturation, protein bodies accumulated to
      high levels both in megagametophyte and embryo cells, whereas starch could no
      longer be detected. Protein levels were high in mature seeds and reached 12% and
      8% of the megagametophyte and embryo DW, respectively. Some sets of polypeptides
      accumulated more specifically at this time in both megagametophyte and embryo.
      Some of these began to first accumulate in the megagametophyte during embryo
      development before their concentration rose in the embryo at cotyledonary stage.
      Others displayed a more specific-embryo accumulation pattern.

PMID- 11975737
TI  - A seedling specific vegetative lectin gene is related to development in Cicer
      arietinum.
AB  - Plant lectins are a group of glycoproteins with the ability to recognize and bind
      carbohydrate ligands. Seed lectins function as storage and defense proteins, but
      the specific function of vegetative lectins is uncertain. In this paper we
      describe the characterization of a clone, CanVLEC, encoding a vegetative lectin
      from chickpea (Cicer arietinum L. cv. Castellana). The expression of the CanVLEC
      gene was specific in seedlings, mostly in hooks and elongating epicotyls, and no
      expression was detected in adult plants. The level of chickpea vegetative lectin
      transcripts in epicotyls decreased through the epicotyl growth suggesting a
      relationship to development. Treatment with indoleacetic acid (IAA) and
      brassinolides (BR), hormones that promoted elongation in chickpea epicotyl,
      increased the level of CanVLEC mRNA, supporting a relationship to growth. CanVLEC
      is drastically down regulated by water deficit ruling out its possible
      involvement in plant response to water stress, unlike other vegetative lectins.
      CanVLEC protein may be targeted to an extracellular location owing to the
      presence of a signal peptide.

PMID- 11975738
TI  - Reduced gravitropism in inflorescence stems and hypocotyls, but not roots, of
      Arabidopsis mutants with large plastids.
AB  - The sites of gravity perception are columella cells in roots and endodermal cells
      in hypocotyls and inflorescence stems. Since plastids are likely to play a role
      in graviperception, we investigated gravitropism in plastid mutants of
      Arabidopsis. Previous studies have shown that the arc6 and arc12 (accumulation
      and replication of chloroplasts) mutants have an average of two large plastids
      per leaf mesophyll cell. In this study, we found that these arc mutants have
      altered plastid morphology throughout the entire plant body, including the cells
      involved in gravity perception. There were no major differences in total starch
      content per cell in endodermal and columella cells of the wild-type (WT) compared
      to arc6 and arc12 as assayed by iodine staining. Thus, the total mass of plastids
      per cell in arc6 and arc12 is similar to their respective WT strains. Results
      from time course of curvature studies demonstrated that the plastid mutation
      affected gravitropism only of inflorescence stems and hypocotyls, but not roots.
      Thus, roots appear to have different mechanisms of gravitropism compared to stems
      and hypocotyls. Time course of curvature studies with light-grown seedlings were
      performed in the presence of latrunculin B (Lat-B), an actin-depolymerizing drug.
      Lat-B promoted gravitropic curvature in hypocotyls of both the WT and arc6 but
      had little or no effect on gravitropism in roots of both strains. These results
      suggest that F-actin is not required for hypocotyl gravitropism.

PMID- 11975739
TI  - A relationship between seed development, Arabinogalactan-proteins (AGPs) and the
      AGP mediated promotion of somatic embryogenesis.
AB  - Arabinogalactan-protein (AGP) epitopes are known to display developmentally
      regulated patterns of expression in several plant tissues. Therefore, AGPs have
      been suggested to play a role in plant development. Somatic embryogenesis is
      regulated by AGPs as well as by EP3 endochitinases. Using four different methods
      we have analysed the composition of AGPs in immature carrot seeds. The results
      obtained show that: (1) the native electrophoretic mobility of such AGPs changes
      during development; (2) AGP epitopes in immature seeds are developmentally
      regulated; (3) enzymatically released fragments of AGPs show that the composition
      of these molecules changes as a function of development; and (4) the biological
      activity of AGPs on the formation of somatic embryos changes depending on the age
      of the seeds. Our results suggest that degradation of maternally derived AGPs
      occurs after fertilization, while cellularization of the endosperm leads to
      synthesis of a new set of AGPs. The presence of an endochitinase cleavage site as
      well as the capacity to increase somatic embryogenesis only occurred in AGPs that
      were isolated from seeds in which the endosperm had been cellularized.
      Apparently, both EP3 endochitinases and somatic embryogenesis-promoting AGPs are
      developmentally regulated in immature carrot seeds.

PMID- 11975740
TI  - Differential responses of Brassica napus and Petunia hybrida to leaf protoplast
      isolation stress.
AB  - Changes in the response to abiotic stress during the isolation of leaf
      protoplasts were compared between a recalcitrant species of Brassica napus and
      regenerating species of Petunia hybrida. Initially, levels of soluble free
      putrescine (put), spermidine (spd) and spermine (spm) in leaves and protoplasts
      were determined. The sum of these three polyamines increased in petunia and B.
      napus leaf protoplasts by 1.6-fold and 1.1-fold, respectively. The soluble free
      fraction of spd and spm decreased in B. napus but not in petunia protoplasts.
      During the isolation of leaf protoplasts from B. napus, the ratio of soluble free
      put to the total PAs almost doubled, but that of spd and spm declined
      significantly. Petunia leaf protoplasts treated with cyclohexylamine (CHA), an
      inhibitor of spermidine synthase, accumulated ammonia and soluble putrescine, but
      lost the soluble spermidine. The soluble polyamine levels of CHA-treated petunia
      leaf protoplasts corresponded with those in B. napus. Leaves were subjected to
      abiotic stress during the isolation of protoplasts, namely wounding and osmotic
      stress which changed soluble free polyamine levels in B. napus and petunia,
      respectively. Both B. napus and petunia leaf protoplasts showed an increase in
      ammonia, but total free amino acid content and activation of proteases were only
      enhanced in B. napus leaf protoplasts. These results suggest that in B. napus
      wounding initiated senescence of leaf protoplasts during their isolation, leading
      to a constant production of ethylene early in the culture.

PMID- 11975741
TI  - Rhizobium colonization induced changes in membrane-bound and soluble
      hydroxyproline-rich glycoprotein composition in pea.
AB  - Abundance and distribution of plant cell surface proteins of the hydroxyproline
      rich glycoprotein (HRGP) class were studied in the pea-Rhizobium symbiosis using
      immunoblot analysis. The MAC 265-epitope was especially abundant in pea root
      nodules containing nitrogen-fixing Rhizobium bacteria. A 180-kDa MAC 265-HRGP
      dominated in pea shoot plasma membranes, while almost no MAC 265-HRGP was
      detected in root plasma membranes. We show here that a major difference between
      the plant-derived peribacteroid membrane of the symbiosomes and the root plasma
      membrane was the presence of a 100-kDa MAC 265-HRGP in the former.
      Arabinogalactan proteins (AGPs), as recognized by the monoclonal antibodies MAC
      207 and JIM 8, were not detected in the peribacteroid membrane, while two
      isoforms (100 and 220 kDa) were detected in shoot and root plasma membranes.
      Specific MAC 265-HRGP isoforms were found in the peribacteroid space fraction of
      the symbiosomes and thus as soluble proteins in the interface between the
      symbionts. The abundance of the MAC 265-epitope was much reduced in non-nitrogen
      fixing nodules when this phenotype resulted from a dicarboxylate transport
      mutation in Rhizobium. There was no reduction in the abundance of the MAC 265
      epitope in non-fixing phenotypes resulting from a mutation in the plant. The
      results suggest that bacterial signals related to the bacterial ability to fix
      nitrogen, might be responsible for the regulation of HRGP expression in root
      nodules.

PMID- 11975742
TI  - Production of buffalo (Bubalus bubalis) embryos in vitro: premises and promises.
AB  - Techniques for in vitro production (IVP) of buffalo embryos adopting the
      procedures developed in cattle have received increasing interest in the recent
      times. A high oocyte maturation, fertilization and cleavage rate and a low rate
      of blastocyst yield and calving following transfer of in vitro produced buffalo
      embryos have been obtained. The efficiency of IVP in buffalo is much lower than
      that in cattle. Several problems need to be resolved before IVP technology can be
      used regularly in buffalo breeding. This review attempts to present an overview
      of the different techniques used in buffalo to produce transferable embryos in
      vitro, namely in vitro maturation and fertilization of immature oocytes and in
      vitro development of the resulting cleaved embryos to the blastocyst stage before
      transfer. The problems associated with IVP, the possible solutions and the new
      biotechniques linked to IVP are discussed.

PMID- 11975743
TI  - Intraperitoneal insemination in mammals: a review.
AB  - This review focuses on factors associated with the development of intraperitoneal
      insemination in mammals. Findings to date indicate that fertility improves as the
      sperm cell concentration rises, but that the optimal sperm number differs in each
      species. Sperm washing before intraperitoneal insemination favours fertility.
      Peritoneal fluid shows a variable effect on spermatozoa, depending on the
      hormonal status of the female. The optimal time for insemination appears to be
      just prior to ovulation. The technique may be performed either through the
      abdominal or the vaginal wall. Verification of sperm deposition in the proximity
      of the ovaries improves fertility rates. Although associated with some risk of
      infection and an immune reaction against spermatozoa, the intraperitoneal
      technique rarely gives rise to severe anaphylactic shock, peritonitis, adhesion
      formation and the production of anti-sperm antibodies and these complications may
      be prevented by adequate sperm pretreatment and antibiotic therapy. The success
      of intraperitoneal insemination in humans, with results comparable with those of
      intrauterine insemination in the treatment of infertility, suggest the potential
      use of this technique in domestic mammals, especially in those in which
      intrauterine insemination poses practical difficulties. Some of the methods
      applied in human intraperitoneal insemination, such as confirming the position of
      the needle in the peritoneal cavity, and sperm pre-treatments might also improve
      results in domestic species. Conversely, the use of the animal model should help
      to develop some aspects of this technique in humans.

PMID- 11975744
TI  - Angiotensin converting enzyme in bovine ovarian follicular fluid and its
      relationship with oestradiol and progesterone.
AB  - CONTENT: The purpose of the present study was to identify angiotensin converting
      enzyme (ACE) in bovine ovarian follicular fluid and to relate the ACE activity to
      the phase of the oestrous cycle, pregnancy, and the follicular fluid
      concentrations of oestradiol and progesterone. The ACE activity was similar to
      that found in bovine serum and was completely inhibited by the specific ACE
      inhibitor captopril. The 50% inhibitory concentration (IC50) was 1.4 x 10(-8)
      mol/l (range 0.8 x 10(-8) to 5.0 x 10(-8) mol/l; n=6), which is similar to that
      found in bovine and human serum. The ACE activity did not differ in the pre
      ovulatory and luteal phase, pregnancy or cystic follicles. It correlated with the
      follicular fluid concentration of progesterone in cycling cows (rho=0.476; p <
      0.005; n=36), but did not correlate with the diameter of the follicles, the
      follicular fluid concentration of oestradiol or the ratio between the oestradiol
      and progesterone concentrations. The demonstration of ACE in bovine ovarian
      follicular fluid provides further evidence for the presence of a local renin
      angiotensin system in the bovine ovary.

PMID- 11975745
TI  - Comparative analysis of protein synthesis, transcription and cytoplasmic
      polyadenylation of mRNA during maturation of bovine oocytes in vitro.
AB  - In many species, large numbers of macromolecules are accumulated during oocyte
      growth. The messenger and ribosomal RNAs produced in these cells are far in
      excess of those necessary to support protein synthesis. Thus, the aim of this
      study was to elucidate the processes of translational regulation during meiotic
      maturation. The relationship between transcription, translation and
      polyadenylation of mRNA during in-vitro maturation (IVM) of bovine oocytes was
      investigated. The results presented here show that overall protein synthesis is
      stimulated during meiotic maturation (approximately three times) concomitantly
      with the onset of germinal vesicle breakdown after 6 to 10 h of IVM. However, in
      metaphase II, the incorporation of [35S]methionine into proteins showed only
      basal levels, as in the germinal vesicle (GV) stage. Furthermore, in the course
      of IVM, de-novo transcription strongly declines as determined by measuring the
      incorporation of [3H]uridine into RNA. In contrast to this finding, the
      incorporation of [3H]adenosine increased and showed a peak during the time
      interval from 6 to 10 h of IVM, parallel with the onset of germinal vesicle
      breakdown (GVBD) and translation. In the further course of maturation, only a
      moderate decrease of [3H]adenosine incorporation was observed. These results
      indicate that (i) translation increased at the time of GVBD; (ii) these processes
      were accompanied by polyadenylation of mRNA; and (iii) although transcription
      declines, polyadenylated mRNA is accumulated until metaphase II (as shown by
      poly(U)-hybridization), in which protein synthesis is low. The correlation of
      these processes is discussed here. A detailed knowledge of the biochemical and
      molecular processes which occur during oocyte maturation can be useful for the
      improvement of IVM conditions.

PMID- 11975746
TI  - Effect of rabbit age on sperm chromatin structure.
AB  - The aim of this study was to determine the relationship between the age of male
      rabbits and the sperm chromatin structure. The studies involved the semen of New
      Zealand White rabbits between 5 and 28 months of age. A flow cytometry and sperm
      chromatin structure assay (SCSA) method was used to determine chromatin
      structure. The results of cytometric chromatin structure assay suggested a
      relatively high stability of sperm chromatin in the rabbit. Between 6 and 16
      months of age, the mean percentage of sperm with damaged chromatin was the lowest
      and ranged from 1.7 to 2.4%. Decreased sperm chromatin stability was found in
      ejaculates taken from male rabbits less than 5 months and more than 20 months of
      age.

PMID- 11975747
TI  - Vitamin A and beta-carotene levels in plasma, corpus luteum and follicular fluid
      of cyclic and pregnant cattle.
AB  - This study was carried out to examine the relationship between the corpus luteum
      (CL) weight, CL and follicle diameters and progesterone, beta-carotene and
      vitamin A levels in reproductive organs of cattle obtained from the
      slaughterhouse. The beta-carotene and vitamin A levels were determined in plasma,
      CL and follicular fluid (FF) using a spectrophotometric method at different
      stages of the oestrous cycle (n=40) and at 3-6 months of pregnancy (n=10). The
      diameters of the CL and follicle were measured using ultrasonography. Plasma
      progesterone concentrations were determined by an enzyme immunoassay method. The
      vitamin A levels of the plasma, CL and FF were not related to each other. The
      highest plasma vitamin A levels were observed in the proestrus and oestrus, at
      which periods follicular activity dominates. The vitamin A levels in the CL and
      FF were negatively related to the weight and diameter of the CL and the diameter
      of follicle, respectively. In contrast to vitamin A, beta-carotene concentrations
      of plasma, CL and FF were significantly correlated with each other. The highest
      beta-carotene levels in the plasma, CL and FF were found during pregnancy when
      there is maximal luteal function, and the beta-carotene level of the CL was
      significantly correlated with the weight and diameter of CL. Furthermore, the
      intrafollicular beta-carotene level was negatively correlated with the follicle
      diameter. There was a positive correlation between plasma progesterone level and
      the weight and diameter of the CL, but a negative correlation between plasma
      progesterone level and follicle diameter. Moreover, plasma, FF and CL beta
      carotene levels were positively correlated with plasma progesterone levels. This
      study revealed that beta-carotene levels in the plasma, CL and FF were influenced
      by the stage of the oestrous cycle or the pregnancy and were related to bovine
      luteal function without depending on vitamin A.

PMID- 11975748
TI  - Comparison of the ability of three radioimmunoassay to detect pregnancy
      associated glycoproteins in bovine plasma.
AB  - CONTENTS: Pregnancy-associated glycoproteins (PAGs) constitute a large family of
      glycoproteins that are synthesized in the superficial layer of the ruminant
      placenta according to a spatial and temporal expression pattern. When PAGs are
      released in the maternal blood they can be used for pregnancy diagnosis,
      pregnancy follow-up and for the monitoring of the trophoblastic function. Three
      different radioimmunoassay systems (RIA 1, RIA 2 and RIA 3) using antisera
      produced against PAG I67 (RIA 1), PAG55+62 (RIA 2) and PAG55+59 (RIA 3) were used
      in this investigation in order to measure the PAG concentration in plasma samples
      withdrawn from pregnant cows and heifers during different periods following
      artificial insemination (AI). These systems were able to detect PAG molecules in
      the maternal blood as early as 21 days after AI in different concentrations (RIA
      1: 0.43 +/- 0.24 ng/ml, mean +/- SD; RIA 2: 0.48 +/- 0.24 ng/ml; RIA 3: 0.64 +/-
      0.37 ng/ml). On days 32 and 42 RIA 2 (4.30 +/- 1.32 ng/ml and 5.56 +/- 1.95
      ng/ml) and RIA 3 (4.17 +/- 1.15 ng/ml and 5.60 +/- 1.89 ng/ml) presented
      significantly (p < 0.0001) higher PAG concentrations than those of RIA 1 (2.43 +/
      0.81 ng/ml and 4.01 +/- 1.48 ng/ml), respectively. After day 21, significant
      correlations (p < 0.0001; r >/= 0.929) were determined between the three systems.
      Additionally the three individual PAG profiles presented in this study showed
      that PAG molecules secreted in the maternal blood between 21 and 50 days after AI
      were better recognized by the RIA 2 and RIA 3 systems. This study clearly
      indicated that the ability of a RIA test to recognize PAG molecules in the
      maternal blood can be improved by carefully selecting the antiserum.

PMID- 11975749
TI  - Tumour necrosis factor-alpha receptors are present in the corpus luteum
      throughout the oestrous cycle and during the early gestation period in pigs.
AB  - To determine the physiological significance of tumour necrosis factor-alpha
      (TNFalpha) in the regulation of luteal functions in pig, this study was conducted
      to identify the presence of functional TNFalpha receptors in porcine corpora
      lutea (CL) throughout the oestrous cycle and the early gestation. The CL were
      isolated from pigs on days 4, 6, 8, 12 or 15 of the oestrous cycle (n=3; day 0 =
      oestrus) and days 15, 20 or 25 of gestation (n=3; day 0 = mating). A Scatchard
      analysis revealed the presence of a high-affinity binding site for TNFalpha in
      all samples (dissociation constant; 2.7 +/- 0.51 to 5.8 +/- 0.50 nM). The
      concentration of TNFalpha receptors was higher on day 15 of the oestrous cycle
      than on days 4 and 8 of the oestrous cycle (p < 0.05). Furthermore, TNFalpha
      receptor concentrations in the CL on days 15, 20 and 25 of gestation were
      significantly lower than on day 15 of the oestrous cycle (p < 0.05). On day 9 of
      the oestrous cycle, exposure of cultured luteal cells to 0.06-60 nM TNFalpha
      stimulated prostaglandin (PG) F2alpha and PGE2 secretion in a dose-dependent
      manner (p < 0.05). These results indicate that functional TNFalpha receptors are
      present in the porcine CL throughout the oestrous cycle and early gestation, and
      suggest that TNFalpha plays one or more physiological roles in regulating CL
      function throughout the oestrous cycle and the early gestation period. In
      addition, TNFalpha receptor concentration in the CL of the late luteal stage (day
      15) of the oestrous cycle was higher than on the respective day in the early
      pregnant pig, suggesting that TNFalpha plays a role in accomplishing luteolysis
      in the porcine CL.

PMID- 11975751
TI  - Effect of mating frequency on sow reproductive performance under field conditions
      and natural mating in large outdoor production units.
AB  - The effect of mating frequency on fertility and litter size of sows, kept in
      outdoor production systems was investigated. Sows that were mated once or twice
      during a single oestrus were included in the study to compare the effect of
      number of matings on farrowing rate and litter size. Natural mating was used
      during the study period. Four groups of sows of parity two or more were either
      mated once 28-30 h after the onset of oestrus or were mated 28-30 h after the
      onset of oestrus and again 24 h later. The farrowing rate did not differ
      significantly between single- and double-mated sows, although a noticeable but
      non-significant depression in farrowing rate was evident between the groups of
      single-mated and double-mated animals. With the exception of total-born litter
      size (p > 0.05), the total number born and number of live-born piglets per litter
      were significantly (p < 0.05) lower in the group of sows that received only one
      mating compared with the double-mated animals. The implication of these results
      is that the double mating by natural service of sows kept in an outdoor
      production systems may improve litter size.

PMID- 11975750
TI  - The effect of pasture nitrate concentration and concentrate intake after turnout
      on embryo growth and viability in the lactating dairy cow.
AB  - This study investigated the effects on embryo growth and survival rate of feeding
      heavily-fertilised spring grass, containing high levels of quickly-degradable
      nitrogen, to pregnant cows. Forty-eight lactating Holstein cows between 2 and 8
      weeks pregnant were turned-out, after a one-week transition period onto high- or
      low-nitrate pasture and fed a high- or low-concentrate supplement. Cows grazing
      the High nitrate pasture had significantly higher milk and plasma urea
      concentrations than cows grazing the Control pasture, while cows which were fed
      less concentrate had a notably higher plasma ammonia. However, there was no
      evidence that an increased quickly-degradable nitrogen (QDN) intake from pasture
      affected embryo survival or growth from 20 days onwards. This suggests that the
      impact of turnout on fertility mainly affects ovulation, fertilisation and/or the
      early embryo.

PMID- 11975752
TI  - Case study: chronic erysipelas of the sow--a subclinical manifestation of
      reproductive problems.
AB  - Systemic infections with Erysipelothrix rhusiopathiae are usually associated with
      skin lesions, vegetative endocarditis and arthritis, but they can also cause
      reproductive symptoms such as abortion, increased stillbirths, and smaller litter
      size. In a large Hungarian breeding unit that had ceased to vaccinate the sows
      against erysipelas, an increased incidence of pre- and post-partal vulval
      discharge, increased weaning-to-oestrus intervals, decreased farrowing rates, and
      reductions in total number of pigets born and live-born litter size were
      reported. Anterior vaginal swabs were obtained from 64 sows shortly before
      parturition and they all yielded heavy growths of E. rhusiopathiae. A vaccination
      programme with a killed vaccine was reinstated and subsequently the incidence of
      vulval discharge and weaning-to-oestrus intervals were decreased and total born
      and live-born litter size were increased. In the absence of a control group
      definitive conclusions can not be made regarding the effect of vaccination
      against E. rhusiopathiae on sow fertility. However, it is not unreasonable to
      suggest that the aetiology of the reduced sow fertility in the present herd did
      involve E. rhusiopathiae and that appropriate vaccinations subsequently protected
      the sows from the disease.

PMID- 11975753
TI  - Receptor revision and systemic lupus.
AB  - Studies over the past 10 years have shown that B cells can undergo secondary
      heavy- or light-chain immunoglobulin (Ig) rearrangements at various stages of
      their normal development, a process termed receptor editing. In the bone marrow,
      this mechanism is important to maintain tolerance because it can extinguish a
      self-reactive specificity without having to physically eliminate a potentially
      autoreactive B cell. In the periphery, secondary rearrangements may also play a
      role in the diversification and maturation of an immune response, although
      conclusive evidence for this process is still required. Individuals with systemic
      autoimmune diseases, such as lupus, show evidence of intricate abnormalities in
      receptor editing. On the one hand, decreased editing may not eliminate the self
      reactive specificities that emerge during B-cell development in the bone marrow.
      Conversely, excessive secondary rearrangements, especially in the periphery where
      tolerance mechanisms are less effective, can result in the production of
      autoantibodies by edited B cells. It will be important to assess whether the
      complex editing defects observed during lupus are a primary susceptibility factor
      to this disease or if they are secondary to other abnormalities of lymphocyte
      development in these autoimmune patients.

PMID- 11975754
TI  - The natural killer cell -- friend or foe in autoimmune disease?
AB  - Autoimmune diseases are chronic conditions resulting from a loss of immunological
      tolerance to self-antigens. Recent observations have supported an ever-broader
      role for innate immune responses in directing and regulating adaptive immunity,
      including responses to self. This review summarizes recent findings supporting
      important functions of natural killer (NK) cells in regulating autoimmunity. A
      close survey of the current literature reveals multiple steps where NK cells can
      regulate inflammation and intervene in loss of self-tolerance. Importantly, the
      findings also caution against inferring a similar role for NK cells in all
      autoimmune phenomena or during separate stages of the same disease. Indeed, NK
      cells may have different influences during the priming and the effector phases of
      disease. Hence, an increased understanding of the involvement of NK cells in
      inflammation and infection should provide new insights into the pathogenesis of
      autoimmune disease.

PMID- 11975755
TI  - The thymus gland: a target organ for growth hormone.
AB  - Increasing evidence has placed hormones and neuropeptides among potent
      immunomodulators, in both health and disease. Herein, we focus on the effects of
      growth hormone (GH) upon the thymus. Exogenous GH enhances thymic
      microenvironmental cell-derived secretory products such as cytokines and thymic
      hormones. Moreover, GH increases thymic epithelial cell (TEC) proliferation in
      vitro, and exhibits a synergistic effect with anti-CD3 in stimulating thymocyte
      proliferation, which is in keeping with the data showing that transgenic mice
      overexpressing GH or GH-releasing hormone exhibit overgrowth of the thymus. GH
      also influences thymocyte traffic: it increases human T-cell progenitor
      engraftment into the thymus; augments TEC/thymocyte adhesion and the traffic of
      thymocytes in the lymphoepithelial complexes, the thymic nurse cells; modulates
      in vivo the homing of recent thymic emigrants, enhancing the numbers of
      fluroscein isothiocyanate (FITC)+ cells in the lymph nodes and diminishing them
      in the spleen. In keeping with the effects of GH upon thymic cells is the
      detection of GH receptors in both TEC and thymocytes. Additionally, data indicate
      that insulin-like growth factor (IGF)-1 is involved in several effects of GH in
      the thymus, including the modulation of thymulin secretion, TEC proliferation as
      well as thymocyte/TEC adhesion. This is in keeping with the demonstration of IGF
      1 production and expression of IGF-1 by TEC and thymocytes. Also, it should be
      envisioned as an intrathymic circuitry, involving not only IGF-1, but also GH
      itself, as intrathymic GH expression is seen both in TEC and in thymocytes, and
      that thymocyte-derived GH could enhance thymocyte proliferation. Finally, the
      possibility that GH improve thymic functions, including thymocyte proliferation
      and migration, places this molecule as a potential therapeutic adjuvant in
      immunodeficiency conditions associated with thymocyte decrease and loss of
      peripheral T cells.

PMID- 11975756
TI  - Age-related changes in human blood dendritic cell subpopulations.
AB  - It is well known that the human immune system is functionally less mature at
      birth and, within the first years of life, undergoes a process of sequential
      development. Two subsets of dendritic cells (DCs) were identified in the blood:
      plasmacytoid and myeloid DCs. DCs stain negative for CD3, CD14, CD16, CD19, CD20
      and CD56, and positive for human leucocyte antigen (HLA)-DR. In addition,
      plasmacytoid DCs strongly express CD123 while myeloid DCs express CD11. The
      number of the two different subsets was measured by flow cytometry in the
      peripheral blood from 44 healthy infants and children, aged 8 months to 18 years.
      While the number of CD11c+ myeloid cells (mean 11 cells/microl) did not change
      with age, the proportion of CD123+ plasmacytoid DCs decreased significantly (P <
      0.001) from about 20 cells/microl to 8 cells/microl with age. In addition, we
      found a direct correlation between the number of plasmacytoid DC and interferon
      (IFN)-alpha production. As the two subsets of DC preferentially recognize
      different pathogens, age-related changes may have an impact on the maturation of
      the immune response.

PMID- 11975757
TI  - Differences between the large and small intestine in the immunodominant amoebic
      proteins recognized by IgG and IgA antibodies in BALB/c mice.
AB  - We have previously reported that there are differences in the number of
      predominant amoebic antigens recognized by serum and small intestinal antibodies
      induced after local and systemic immunization with glutarldehyde-fixed Entamoeba
      histolytica trophozoites (GFT) in BALB/c mice, by an immunoblot analysis.
      Moreover, by enzyme-linked immunosorbent assay (ELISA) analysis, we found
      differences in the antiamoebic antibody isotype patterns elicited at the large
      and small intestines. To further characterize the antiamoebic immune response
      induced in BALB/c mice, after local (oral and rectal) and systemic
      (intraperitoneal and intramuscular) immunization with GFT, we performed an
      immunoblot analysis of the amoebic proteins predominantly recognized by
      immunoglobulins (Ig)G, IgA and IgM in the serum and in the small and large
      intestines. The present work shows differences between the large and small
      intestine in the IgG- and IgA-antibody recognition pattern of amoebic proteins,
      thus confirming and extending our previous findings supporting the
      compartmentalization of the intestinal immune response. Furthermore, our reported
      observation that there are differences in the amoebic proteins predominantly
      recognized by antibodies of different isotypes was extended to the intestines, as
      some proteins with relative molecular weights of 24-25, 66, 140 kDa are strongly
      recognized by IgG but not by other antibody isotypes.

PMID- 11975759
TI  - Testicular-associated immune deviation: flushing of the testicular lymph
      sinusoids induces immunosuppression and inhibits formation of EAE in SJL mice.
AB  - Injection of antigen into the testis has been previously proved to induce
      systemic tolerance in rats. Testicular-associated immune deviation (TAID) has
      thus far been induced and studied only in the rat and the present study was
      planned to study if TAID could be induced in mice as well. In addition, it was
      studied if TAID is organ-specific. Mouse spinal cord homogenate (MSCH), as well
      as phosphate-buffered saline (PBS), was injected into the testes of SJL and
      BALB/c male mice before the induction of experimental allergic encephalomyelitis
      into the animals. The control animals received MSCH intramuscularly into the
      hamstring muscles. The animals were followed and graded daily for symptoms
      attending the next 30 days. In the SJL strain, mice treated with an
      intratesticular (i.t.) MSCH injection prior to the induction of experimental
      autoimmune encephalomyelitis (EAE) had the shortest duration of symptoms and the
      longest time to the onset of the first symptoms. In addition, the mice injected
      i.t. with PBS had as mild symptoms as those injected with MSCH. There was a
      statistically significant difference, however, between the groups injected either
      with MSCH or PBS intratesticularly. In general, mice treated with an
      intramuscular injection of MSCH got sick first, and had the most severe symptoms
      for the longest duration of time. In the case of the BALB/c mice, there were no
      statistical differences between the groups investigated. It is concluded that
      TAID is a testis- and strain-specific phenomenon in the mouse, and not specific
      to the rat. In addition, i.t. injection of PBS is just as effective in creating
      tolerance against EAE as i.t. injection of MSCH in the SJL mice.

PMID- 11975758
TI  - An established immune response against ovalbumin is suppressed by a transferable
      serum factor produced after ovalbumin feeding: a role of CD25+ regulatory cells.
AB  - We have previously demonstrated that rats fed ovalbumin (OVA) develop a
      tolerogenic activity in serum, which upon transfer induces tolerance to OVA and
      suppression of the immune response to a bystander antigen. Here, we have extended
      these studies and analysed if the tolerogenic activity in serum could suppress an
      established immune response in the recipients. Rats were immunized with OVA, 4
      and 1 week prior to the transfer of serum from either OVA-fed or control animals.
      Rats that received serum from OVA-fed donors had significantly lower delayed-type
      hypersensitivity (DTH) reaction against OVA 1 week after the serum transfer
      compared with the controls, and the levels of immunoglobulin (IgG) anti-OVA
      antibodies were significantly lower 2 and 4 weeks after serum transfer. Monomeric
      OVA in amounts corresponding to the OVA transferred with serum did not induce the
      reduction of DTH response or IgG anti-OVA antibody levels. In vitro, the
      proliferation of OVA-stimulated spleen cells, taken from recipients of
      tolerogenic serum, was significantly lower compared with spleen cells from the
      controls. The in vitro suppression seemed to be mediated by a population of CD25+
      cells, because the removal of such cells from OVA-stimulated spleen cell
      suspensions resulted in increased proliferation in cultures from rats receiving
      tolerogenic serum. Our results showed that the tolerogenic serum factor can
      suppress an established immune response in recipient animals, possibly through
      induction of regulatory CD25+ cells. Whether this capacity might be used to
      influence chronic inflammatory conditions needs to be investigated.

PMID- 11975760
TI  - Enhanced inhibition of tumour growth and metastasis, and induction of antitumour
      immunity by IL-2-IgG2b fusion protein.
AB  - Cytokine-immunoglobulin (Ig)-fusion proteins have attracted increasing interest
      as antitumour agents. Here, we have investigated the antimetastatic and
      antitumour responses elicited in vivo by mammary adenocarcinoma cells (TS/A)
      engineered to secrete interleukin (IL)-2-IgG fusion proteins. TS/A cells were
      transfected with DNA coding for IL-2-IgG2b, IgG2b or IL-2, and injected
      subcutaneously into syngeneic mice. Animals injected with TS/A-IL-2 or TS/A-IL-2
      IgG2b both efficiently rejected tumours, whereas treatment with parental cells or
      TS/A-IgG2b was lethal. Interestingly, only mice vaccinated with IL-2-IgG2b fusion
      protein-secreting cells showed a long-lasting protective immunity against a later
      challenge with parental tumour cells. Moreover, the metastatic potential of TS/A
      IL-2-IgG2b-transfected cells was dramatically decreased compared with TS/A-IL-2
      cells, with a virtual absence of lung metastases after intravenous injection.
      Adenocarcinomas secreting IL-2-IgG2b exhibited a more prominent, early and
      persistent infiltration of CD4+, CD8+ and natural killer (NK) cells than TS/A-IL
      2 cells. Therefore, upon transfection into adenocarcinoma cells, the IgG2b part
      of IL-2 fusion protein exerts intriguing added antitumour properties over IL-2
      alone, thus contributing to a long-lasting tumour immunity, probably by the
      recruitment of specific immune effector cells. These findings suggest a promising
      new oncotherapeutic strategy for poorly immunogenic tumours: vaccination with
      tumour cells engineered to secrete IL-2-IgG2b fusion protein.

PMID- 11975761
TI  - Spontaneous downregulation of antibody/autoantibody synthesis in susceptible mice
      upon chronic exposure to mercuric chloride is not owing to a general
      immunosuppression.
AB  - Administration of mercuric chloride into susceptible rats and mice induces a
      systemic autoimmune disease, which is characterized by a T-cell-dependent
      polyclonal B-cell activation, an increase in serum levels of immunoglobulin
      (Ig)G1 and IgE, production of antibodies of different specificities and
      development of renal IgG deposits. A peculiar feature of mercury-induced
      autoimmunity is that the polyclonal B-cell activation spontaneously disappears in
      spite of continuous injection of mercury. The exact mechanism(s) for
      autoregulation of mercury-induced autoimmunity is not well understood. In the
      present study, we analysed the regulation of mercury-induced immune/autoimmune
      responses in mice and tested whether spontaneous downregulation of these
      responses is owing to a general immunosuppression. Mercury-susceptible [SJL (H
      2s)] and -resistant [DBA/2 (H-2d)] mice were injected with mercury for 4, 10, 15
      and 17 weeks. Immune/autoimmune responses were monitored in these mice.
      Thereafter, mercury-injected mice for 17 weeks were further immunized with horse
      red blood cells (HRBC) to study whether the subsequent humoral immune response to
      a foreign antigen is suppressed. We found that except for IgG1 anti-nucleolar
      antibody production and renal IgG1 deposition, other characteristics of mercury
      induced autoimmunity were downregulated in SJL (H-2s) mice after chronic
      treatment with mercury. However, these mice did not show any reduction in the
      number of splenic antibody-secreting cells and/or in serum titres of specific
      IgM, IgG1 and IgG2a anti-HRBC antibodies in response to HRBC as compared with
      naive mice. Similarly, in mercury-resistant DBA/2 (H-2d) mice, chronic treatment
      with mercury did not either suppress specific antibody responses against HRBC.
      Our findings show that the autoregulation of mercury-induced immune/autoimmune
      responses observed after chronic treatment with mercury is not owing to a general
      immunosuppression.

PMID- 11975763
TI  - Cardiopulmonary resuscitation 2000.

PMID- 11975764
TI  - If LDL-C is the answer...what was the question? What do the data really show?
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are
      frequently utilized in the treatment of hypercholesterolemia. With recently
      completed statin clinical cardiovascular outcomes data available, the purpose of
      this review is to analyze the relative benefits of each molecule and to determine
      whether "lower is better" is a correct hypothesis for secondary prevention.
      Twenty-one clinical studies, each with a duration of statin therapy of 6 months
      or longer, were reviewed, and the pharmacologic effects of these agents on
      cardiovascular outcomes was examined. As evaluated by study drug, statistical
      event reduction was achieved in seven of nine pravastatin studies, one of three
      simvastatin studies, one of six lovastatin studies, zero of two fluvastatin
      studies, and zero of one atorvastatin study. Pravastatin was the only statin
      proven statistically to reduce events in both primary and secondary prevention.
      Thus, all of the statins do not appear to be the same in terms of their ability
      to reduce cardiovascular events. Until head-to-head trials have been completed,
      these clinical outcomes data suggest that in patients with severe
      hypercholesterolemia who require high-dose statin therapy, simvastatin 80 mg each
      evening would appear to be the agent of choice. However, pravastatin 40 mg daily
      at bedtime appears to be a unique molecule, with the strongest evidence for event
      reduction in the majority of patients with moderate hypercholesterolemia with, or
      who are at risk for, coronary heart disease.

PMID- 11975765
TI  - Effects of garlic extract (Allium sativum) on neutrophil migration at the
      cellular level.
AB  - Studies of the effects of garlic extract on oxidative and lipoprotein levels have
      yielded widely different findings. Leukocytes play an important role during many
      processes, including inflammation. They migrate from intravascular spaces into
      tissues and attack microorganisms. In a recent study, the inhibitory effects of
      the nonsteroidal antiinflammatory drug, ibuprofen, on leukocyte transmigration
      were demonstrated using an in vitro assay. Little is known about the cellular
      effects of garlic extracts (Allium sativum). The aim of the current study was to
      investigate the influence of garlic extract on leukocyte migration through
      endothelial cell monolayers and thereby evaluate a possible role in inflammatory
      processes. Human umbilical endothelial cells were cultured on microporous
      membranes to make an endothelial cell monolayer (ECM). Freshly isolated
      neutrophils were used in a recently described migration assay. The amount of
      untreated neutrophils migrating through the untreated ECM was used as control and
      set at 100%. Neutrophils and/or ECM were pretreated with garlic extract using
      moderate, higher, and lower concentrations. Moderate plasma concentrations of
      garlic extract inhibited neutrophil migration through ECM significantly (64 +/-
      5.8% standard deviation [SD]; P < 0.05) when both cell types were treated, (a
      situation that may have clinical relevance). Treating either neutrophils or ECM
      alone showed significant reductions in migratory rate (neutrophils treated alone:
      81 +/- 7.7% SD, P < 0.05; ECM alone: 70 +/- 6.7%, P < 0.05). Thus, garlic extract
      is identified as a potent inhibitor of leukocyte migration through endothelial
      cell monolayers. Treatment of both cell types has an additive effect. Endothelial
      cells seem to be more affected than neutrophils. Further investigations are
      necessary to understand the potential clinical consequences.

PMID- 11975767
TI  - Anomalous origin of the left main coronary artery from the right sinus of
      Valsalva: disabling angina and syncope with noninterarterial courses case report
      of two patients.
AB  - Anomalous origin of the left main coronary artery from the right sinus of
      Valsalva or the right coronary artery is a rare coronary anomaly. This anomaly
      has been associated with sudden cardiac death in younger patients, depending on
      its course relative to the pulmonary artery. The authors report this rare anomaly
      in two patients. It presented as unstable angina in the first patient with a
      septal course. In the second patient, it presented as syncope with an anterior
      free wall course and absent left circumflex artery. A septal course causing
      unstable angina has not been reported previously.

PMID- 11975766
TI  - The intermediate CCU admission: a preliminary study.
AB  - In the current health care era, increasing emphasis is being placed on cost
      reduction. Admitting only high-risk patients to coronary care units (CCU) may
      reduce hospital costs and charges without adverse clinical outcomes. Recently,
      guidelines published by the Agency for Healthcare Policy and Research (AHCPR) on
      suggest that intermediate-risk patients be admitted to an intermediate CCU
      (ICCU), but the safety and appropriateness of this approach has not been
      prospectively evaluated. The authors hypothesized that admitting intermediate
      risk patients with to an ICCU would be cheaper than admitting to a CCU with
      comparable safety supporting AHCPR guidelines. To evaluate this, a retrospective
      cohort study was conducted. Two hundred forty-three intermediate-risk patients
      consecutively admitted to the CCU (n = 134) and admitted to the ICCU (n = 109)
      between June 1, 1992 and April 1, 1994 were compared using AHCPR definitions of
      intermediate risk and a previously published risk prediction model to exclude
      both very low- and high-risk patients. Extensive demographic, clinical, and
      diagnostic testing, and treatment, procedural, and outcome data were collected by
      a trained nurse data collector at the time of admission. Fifty-nine percent of
      all study patients had at least two coronary risk factors. Twenty-one percent had
      diabetes. Ninety-eight percent had at least one AHCPR intermediate risk factor
      for cardiac complications. The two groups (CCU versus ICCU) were quite similar in
      baseline characteristics: men (56 versus 55%), age (57 +/- 17 versus 60 +/- 17
      years), diabetes (22 versus 20%), previous myocardial infarction (30 versus 36%),
      previous coronary artery surgery (21 versus 21%), and rest pain (78 versus 66%).
      The use of coronary angiography (44 versus 52%), angioplasty (24 versus 21%), and
      coronary artery surgery (13 versus 11%) were also similar. The incidence of
      myocardial infarction or death was similar (3 versus 5%), and length of stay was
      also similar between groups (6.7 +/- 4.2 versus 6.5 +/- 4.1 days), but cost was
      less for patients admitted to the ICCU ($13,481 +/- 9,450 versus $10,619 +/-
      8,732, P < 0.015). These preliminary data suggest intermediate-risk patients, as
      identified by AHCPR guidelines, can be treated in an ICCU at lower cost than in a
      CCU, with reasonable safety. A small incidence of myocardial infarction in ICCU
      admitted patients occurs, requiring availability of cardiac resuscitation and
      continued monitoring of electrocardiographic and enzymatic abnormalities.
      Admission to ICCU poses no barrier to recommended patient evaluation and
      management.

PMID- 11975768
TI  - Antioxidant vitamins and enzymatic and synthetic oxygen-derived free radical
      scavengers in the prevention and treatment of cardiovascular disease.
AB  - Oxygen-derived free radical formation can lead to cellular injury and death.
      Under normal situations, the human body has a free radical scavenger system
      (catalase, superoxide dismutase) that can detoxify free radicals. Antioxidant
      vitamins and enzymatic and synthetic oxygen-derived free radical scavengers have
      been used clinically to prevent the formation of oxidized LDL and to prevent
      reperfusion injury, which is often caused by free radicals. In this article, the
      pathogenesis of free radical production and cell injury are discussed, and
      therapeutic approaches for disease prevention are presented.

PMID- 11975769
TI  - Innovative pharmacologic approaches to cardiopulmonary resuscitation.
AB  - The survival rate of patients undergoing cardiopulmonary resuscitation is 5 to
      15%. New cardiopulmonary resuscitation treatment approaches under investigation
      include the use of vasopressin as a vasopressor, amiodarone for the treatment of
      ventricular tachyarrhythmias, and adenosine antagonists (i.e., theophylline) for
      bradyasystolic rhythms. More innovative approaches include the use of thyroid
      hormone and endothelin.

PMID- 11975770
TI  - Verapamil revisited: a transition in novel drug delivery systems and outcomes.
AB  - Verapamil, the oldest calcium-channel blocker, is now being rediscovered and
      reevaluated in the light of new novel drug delivery systems and new evidence
      based trials. Verapamil, a phenylalkylamine, is useful in the treatment of
      hypertension, stable angina, and narrow QRS supraventricular arrhythmias. This
      calcium antagonist is effective in both young and old, and both black and white
      hypertensive patients, and is free of metabolic side effects. Verapamil has a
      well-documented history as an effective antianginal agent when directly compared
      with a beta-blocker, and is more effective in reducing myocardial ischemia
      compared with amlodipine monotherapy. Because of the short half-life of
      verapamil, drug delivery systems are used to prolong the duration of action.
      Novel drug delivery systems using encapsulated beads or a modified osmotic pump
      have been designed to be taken at nighttime to provide maximal blood pressure
      reduction in the early morning hours and effective 24-hour blood pressure
      control, and to avoid excessive blood pressure reduction during sleep. The
      Verapamil in Hypertension and Atherosclerosis Study has documented equivalent
      effectiveness of verapamil compared with chlorthalidone, but showed superior
      plaque regression and reduced events in subjects with the greatest plaques with
      verapamil treatment. The Angina Prognosis Study in Stockholm, comparing verapamil
      and metoprolol for stable angina, found no difference in total cardiovascular
      mortality or combined cardiovascular events. Other large ongoing randomized,
      multicenter trials, including Controlled-Onset Verapamil Investigation of
      Cardiovascular Endpoints and the International Verapamil-Trandolapril Study, will
      expand our knowledge of the role of verapamil in the treatment of hypertension.

PMID- 11975772
TI  - Management of unstable angina in 2001.

PMID- 11975771
TI  - Colesevelam: a new bile acid sequestrant.
AB  - Coronary heart disease is the most prevalent form of cardiovascular disease in
      the United States. Hyperlipidemia--specifically, increased total and low-density
      lipoprotein cholesterol levels--positively correlates with the development of
      coronary heart disease. Colesevelam, a nonabsorbed, water-insoluble polymer, is a
      new bile acid sequestrant that is effective in lowering total and low-density
      lipoprotein cholesterol levels. In several short-term, placebo-controlled
      studies, colesevelam has decreased total cholesterol levels by approximately 6 to
      10% and low-density lipoprotein cholesterol levels by approximately 9 to 20%.
      When given in combination with atorvastatin, lovastatin, or simvastatin, low
      density lipoprotein cholesterol levels were decreased more than with colesevelam
      alone. Its unique hydrogel formulation may also minimize the potential for
      gastrointestinal adverse effects, which are common with other bile acid
      sequestrants. There have been few published studies available concerning this
      drug; no long-term studies and few large-scale studies have been published.

PMID- 11975773
TI  - Use of intracoronary electrocardiography for detecting ST-T, QTc, and U wave
      changes during coronary balloon angioplasty.
AB  - Intracoronary electrocardiography (IC-ECG) is a more sensitive method than
      surface ECG to detect electrical changes during percutaneous transluminal
      coronary angioplasty (PTCA). It also provides direct monitoring of ST-T segment,
      QTc intervals, and U-wave genesis during balloon inflation. These changes are
      reflective of myocardial ischemia. The authors studied the effect of transient
      myocardial ischemia on ST-T segment, QTc intervals, and U-wave appearance by
      comparing standard and perfusion balloon angioplasty. PTCA of left anterior
      descending artery was performed in 14 patients using the standard balloons and in
      11 patients using the perfusion balloons. Patients with perfusion balloon
      angioplasty had less ST-T elevation (0.15 +/- 0.05 mV versus 1.04 +/- 0.19 mV, P
      < 0.001), less QTc-shortening intervals (0.01 +/- 0.02 seconds versus -0.05 +/-
      0.04 seconds, P < 0.001), and less positive U waves (two versus nine). The
      authors concluded that balloon angioplasty with perfusion balloons is associated
      with less ischemia as reflected by ST-T, QTc-shortening intervals, and U-wave
      changes. There was more positive U-wave appearance with the standard balloon
      angioplasty, which implies more ischemia. In addition, QTc-shortening intervals
      are associated with the development of U waves during standard balloon
      angioplasty. These findings suggest that IC-ECG is a sensitive tool in detecting
      myocardial ischemia. IC-ECG may also help to clarify the nature of chest pain
      during PTCA in some patients. Like QT dispersion (QTd), QTc-shortening intervals
      and new U waves can have prognostic implications and additional studies are
      needed to define this role.

PMID- 11975774
TI  - HbA1c predicts length of stay in patients admitted for coronary artery bypass
      surgery.
AB  - Diabetes mellitus is associated with coronary artery disease, and diabetic
      patients are frequently referred for coronary bypass graft surgery. It is well
      known that HbA1c, which reflects long-term glycemic control, is related to
      diabetic morbidity and mortality. It is not known whether HbA1c is related to
      postoperative length of stay among patients who undergo coronary artery bypass
      surgery. The authors evaluated 135 patients who underwent bypass surgery at the
      Westchester Medical Center (Valhalla, NY). HbA1c was measured in all patients
      preoperatively; a value of 7% or greater was used as a threshold for uncontrolled
      hyperglycemia. A postoperative length of stay of 6 days or more was used as the
      cutoff for an extended length of stay. Linear regression was used to assess the
      relationship between HbA1c, adjusted for age, and length of stay in days.
      Logistic regression, with length of stay a binary variable <6, > or =6 days, was
      used to assess the accuracy of HbA1c <7%, > or =7%, adjusted for age, in
      predicting length of stay. An HbA1c of 7% or greater was found to be a strong
      predictor of a length of stay of 6 days or longer. These data suggest that HbA1c
      can be used as a surrogate marker for cardiac and noncardiac morbidity that
      prolongs hospitalization after coronary artery bypass surgery.

PMID- 11975775
TI  - Relationship between cytokine levels and coronary artery disease in women.
AB  - Inflammation is thought to have a role in the pathogenesis of atherosclerotic
      coronary artery disease (CAD), and the measurement of markers of inflammation has
      been suggested to improve the identification of individuals at risk for this
      disease. The incidence of CAD in women is not accounted for by conventional risk
      factors, and the association of CAD and the antiinflammatory cytokine
      transforming growth factor beta1 (TGF-beta1) in this population is unknown.
      Associations among TGF-beta1, the inflammatory cytokine tumor necrosis factor
      alpha (TNF-alpha), and CAD severity in inner city women were examined. Fifty
      three women requiring angiography (mean age, 60.7 years) were stratified as
      having on of the following conditions: 0 vessel disease (VD) (n = 20), 1 (VD) (n
      = 10), 2 VD (n = 9), or 3 VD (n = 14). Fasting serum cytokine levels were
      determined by enzyme-linked immunosorbent assay. Serum TGF-beta1 was lower in
      patients with extensive disease (2 and 3 VD versus 0 and 1 VD). The lowest TGF
      beta1 levels (<30 ng/mL) were in the 2 and 3 VD groups. In contrast, in the 0 and
      1 VD groups, TGF-beta1 was above 41 ng/mL. Serum TGF-beta1 correctly classified
      the severity of CAD in 62.3% of patients, with a predictive threshold of 58 ng/mL
      by discriminant function analysis. TGF-beta1 may be a determinant of clinical
      events and outcome in CAD in women.

PMID- 11975776
TI  - Subcutaneous emphysema and pneumomediastinum: a cause of low-voltage
      electrocardiogram.
AB  - The authors report the occurrence of diffuse low voltage and the loss of R-waves
      in the precordial leads in a standard 12-lead electrocardiogram, suggestive of an
      anterior wall myocardial infarction, in a patient with subcutaneous emphysema and
      pneumomediastinum.

PMID- 11975777
TI  - Perioperative considerations for the patient taking herbal medicines.
AB  - There has been a significant increase in the proliferation and use of dietary
      supplements known as neutraceuticals. Since 1994, herbal products have been
      regulated by the Dietary Supplement Health and Education Act (DSHEA), which does
      not require burden of proof to demonstrate premarketing safety and efficacy
      studies. Scientific literature and government policies have not adequately
      addressed this fast-emerging group of more than 20,000 health supplements. Lack
      of purity and standardization of these agents, combined with minimal education in
      traditional homeopathic medical education, has led to serious health-related
      problems including arrhythmias, cardiovascular compromise, strokes, and deaths.
      Even though 30% of our traditional medicines are derived from botanicals, most
      physicians are either unfamiliar or unwilling to develop any level of expertise
      with neutraceuticals. A review emphasizing perioperative considerations is
      provided of the history of herbal medicines, governmental policies, and specific
      herbal agent-drug interactions.

PMID- 11975778
TI  - Coronary heart disease in African Americans.
AB  - African Americans have the highest overall mortality rate from coronary heart
      disease (CHD) of any ethnic group in the United States, particularly out-of
      hospital deaths, and especially at younger ages. Although all of the reasons for
      the excess CHD mortality among African Americans have not been elucidated, it is
      clear that there is a high prevalence of certain coronary risk factors, delay in
      the recognition and treatment of high-risk individuals, and limited access to
      cardiovascular care. The clinical spectrum of acute and chronic CHD in African
      Americans is similar to that in whites. However, African Americans have a higher
      risk of sudden cardiac death and present more often with unstable angina and non
      Q-wave myocardial infarction than whites. African Americans have less obstructive
      coronary artery disease on angiography, but may have a similar or greater total
      burden of coronary atherosclerosis. Ethnic differences in the clinical
      manifestations of CHD may be explained largely by the inherent heterogeneity of
      the coronary syndromes, and the disproportionately high prevalence and severity
      of hypertension and type 2 diabetes in African Americans. Identification of high
      risk individuals for vigorous risk factor modification-especially control of
      hypertension, regression of left ventricular hypertrophy, control of diabetes,
      treatment of dyslipidemia, and smoking cessation--is key for successful risk
      reduction.

PMID- 11975779
TI  - Cardiac assist devices for end-stage heart failure.
AB  - Cardiac assist devices have become an important therapy for patients with end
      stage cardiac failure. These devices continue to evolve. Most current devices
      provide temporary, left-sided support for patients with cardiogenic shock from
      postcardiotomy syndrome or for patients awaiting cardiac transplantation. The two
      most frequently used left ventricular assist devices as a bridge to transplant
      are the Thermocardiosystems (HeartMate I) and the Novacor devices. The selection
      criteria for the use of these devices and treatment of these patients will be
      reviewed. Additionally, other currently available devices and future devices are
      also presented and discussed.

PMID- 11975780
TI  - Unstable angina pectoris and non-Q-wave myocardial infarction.
AB  - Unstable angina pectoris and non-Q-wave myocardial infarction are clinical
      syndromes that share many pathophysiologic and clinical features. In the spectrum
      of coronary artery disease, these syndromes lie between chronic stable angina and
      Q-wave myocardial infarction. Although both conditions are associated with
      significant morbidity and mortality, patients presenting with these syndromes can
      be further risk stratified into higher and lower risk based on a number of
      readily available clinical features and biochemical parameters. Such risk
      stratification can allow for more tailored treatment and better resource
      allocation. Although routine early coronary angiography and revascularization has
      not been shown to be superior to conservative management, certain high-risk
      patients may benefit from a more aggressive strategy. Medical therapy with the
      use of antiplatelet, anticoagulant, and antiischemic agents remains the
      cornerstone of emergent treatment for patients presenting with these syndromes.
      The recent demonstration of a reduction in both morbidity and mortality with the
      glycoprotein IIb/IIIa antagonists has further expanded the armamentarium of
      available agents. Following initial stabilization, risk stratification with
      stress testing can help identify patients with a large residual ischemic burden
      who may benefit from coronary angiography with revascularization if feasible.

PMID- 11975782
TI  - The kidney in the pathophysiology and treatment of cardiovascular disease.

PMID- 11975781
TI  - Bivalirudin: a new approach to anticoagulation.
AB  - Bivalirudin is one of the first of a new class of anticoagulants known as direct
      thrombin inhibitors. These drugs are able to overcome many of the shortcomings of
      traditional heparin anticoagulation by virtue of this unique mechanism of action.
      Bivalirudin is a semisynthetic derivative of hirudin, a modified component of
      leech saliva. Hirudin has been plagued by bleeding complications, likely due to
      its high affinity for thrombin. Bivalirudin has lower thrombin affinity than
      hirudin and therefore is believed to be a much safer compound. Bivalirudin has
      been shown to be a very effective anticoagulant in laboratory models, though its
      clinical efficacy remains to be fully proven. Bivalirudin has been studied in the
      setting of coronary angioplasty, unstable angina, and acute myocardial infarction
      and has shown some promise in many of these settings, particularly in preventing
      complications of percutaneous coronary interventions. Bivalirudin has
      consistently shown less major bleeding compared with standard heparin, although
      limitations in study methodologies somewhat hinder an accurate interpretation of
      this finding. Larger-scale studies are indicated and are currently being
      performed, the results of which will more definitively define the role of
      bivalirudin for the treatment of cardiovascular disease.

PMID- 11975783
TI  - Student research projects and theses: should they be a requirement for medical
      school graduation?
AB  - From 1981 to 1994, 69 fourth-year students at the Albert Einstein College of
      Medicine participated in a 6-month medical school research project (MSRP) with
      the same mentor. Students could choose an original project or library project,
      and were required to prepare a written report suitable for submission to a peer
      reviewed journal. In this article, it is assessed whether a mandatory fourth-year
      MSRP might substitute for traditional clinical electives. Student reactions to
      the experience were ascertained by using the responses to an open- and closed
      ended questionnaire regarding skills gained by doing MSRPs, the impact on their
      careers, and their relationship to the mentor. Eighty-nine percent of the
      students responded that MSRPs increased their ability to formulate a hypothesis,
      91% reported that this project increased their ability to conduct a literature
      search, 95% felt that MSRPs increased their knowledge of research techniques, and
      91% reported having improved data collection skills after completing these
      projects. Students also reported that MSRPs increased their ability to critically
      evaluate the literature (95%) or to work independently (93%), and 89% responded
      that the project improved their ability to evaluate their individual strengths
      and weaknesses. Eighty-nine percent reported that the project increased their
      ability to write a research paper (34% of projects were original research, 35%
      were literature reviews, and 30% both original research and literature reviews).
      Thirty-three percent of respondents reported having some kind of problem
      completing their projects, and 90% of project reports were accepted for
      publication in peer-reviewed journals. Ninety-one percent of students responded
      that they had received appropriate guidance from their mentor, and 73% met with
      him at least once a week. Seventy-three percent described a relationship with the
      mentor that went beyond project advising. Eighty-five percent responded that the
      project impacted their careers in medicine, 97% felt that the research experience
      was a useful replacement for fourth-year electives, and 91% felt they were as
      well prepared for residency training as their classmates who had regular fourth
      year electives without research. Fifty percent of students indicated that
      completion of an independent research project should not be required for
      graduation, whereas 18% responded it should be a requirement and 32% were
      undecided. Incorporating an MSRP in the fourth year appears to increase research
      skills and is considered to be a useful replacement for traditional elective
      rotations. The MSRP impacts favorably on future careers; however, many students
      do not think it should be a mandatory requirement for graduation from medical
      school.

PMID- 11975784
TI  - Anterior mitral valve aneurysm: a subaortic complication of aortic valve
      endocarditis: a case report and review of literature.
AB  - Mitral valve aneurysm is a rare cause of mitral regurgitation, and is usually
      associated with aortic valve endocarditis. Prompt diagnosis and early surgical
      treatment can prevent complications such as embolization and rupture of the
      aneurysm. The authors report a case of aortic valve endocarditis and mitral valve
      aneurysm in a patient who initially presented with urinary tract infection.

PMID- 11975785
TI  - Inpatient or outpatient initiation of antiarrhythmic medications: why the
      controversy?
AB  - The decision of whether to initiate antiarrhythmic medications in or out of the
      hospital for patients with atrial fibrillation remains an issue of significant
      controversy. The current review analyzes the available data pertaining to the
      safety of antiarrhythmic agent initiation in patients with atrial fibrillation
      and provides a practice guideline.

PMID- 11975786
TI  - Disease management and pharmacoeconomics as tools for mass prevention of
      hypertensive complications.
AB  - Hypertension has been identified as a major predictor of cardiovascular disease,
      which is a worldwide cause of morbidity and premature mortality. Optimal
      management of hypertension involves finding a balance among the benefits, risks,
      and costs of disease treatment and prevention of hypertensive sequelae. Cost
      effectiveness analysis helps to clarify the trade-offs between the costs and
      benefits of treatment and also to evaluate the effects on quality of therapy.
      Disease management programs that incorporate pharmacoeconomic analysis and
      computerized methods of targeting patients at high risk of hypertensive sequelae
      are useful and cost-effective tools. Critical to these cost-effectiveness
      analyses and disease management programs are the expected benefits attributable
      to blood pressure reduction. The utility of these programs in helping to
      determine which patients will benefit from intensive intervention depends to a
      great extent on the assumptions made and the quality of the data used for the
      analyses--that is, the degree to which the data are evidence based.

PMID- 11975788
TI  - Adverse effects of herbal treatment of cardiovascular disease: what the physician
      must know.
AB  - The increasing use of herbal products by patients with cardiovascular disease
      represents a clinical challenge to physicians. The use of herbal products is
      increasing in our society, and less than 50% of patients using herbal products
      report this information to their physicians. In addition, physicians often lack
      the knowledge base for herbal medications to effectively counsel patients
      regarding adverse effects and potential herb-drug interactions. This article
      reviews Western and traditional Chinese herbs that are commonly used by patients
      with cardiovascular diseases, herbs noted to have adverse cardiovascular effects,
      and herbs that may potentially interact with commonly prescribed cardiovascular
      medications.

PMID- 11975787
TI  - Cardiovascular considerations with anthracycline use in patients with cancer.
AB  - Anthracyclines are important chemotherapeutic agents that are used for the
      treatment of various malignancies in both adults and children, but their
      usefulness has been limited by cardiotoxicity that is usually dose related.
      Oxidative injury appears to be the cause of myocardial dysfunction when using
      these drugs. Screening for early myocardial injury with troponin testing,
      echocardiography, and radionuclide examinations has reduced the incidence of
      chronic cardiac dysfunction. Various anthracycline analogues have been developed
      that have less cardiotoxicity. Dexrazoxane, an iron chelator, and the
      radioprotective agent amifostine protect against cardiac injury, thus allowing
      the use of higher doses of anthracyclines. Other strategies that have been
      evaluated are dietary glutamine supplementation and the use of the antioxidant
      probucol.

PMID- 11975789
TI  - Endothelin as a therapeutic target in the treatment of cardiovascular disease.
AB  - Endothelins, a family of peptides derived from the vascular endothelium and
      smooth muscle cells possess vasoconstrictor and mitogenic properties. By acting
      predominantly in a paracrine fashion, these peptides activate specific receptors
      and have protean effects in normal and diseased organ systems. The wide
      distribution of these receptors in various tissues mediate the multiplicity of
      physiologic actions attributed to endothelins. Much of our understanding about
      endothelins has come from the development of an array of receptor-specific and
      mixed receptor antagonists. Based on the promising results from animal studies,
      active research and drug development programs are under way to investigate the
      clinical potential of endothelin antagonism for treatment of cardiovascular
      disease.

PMID- 11975792
TI  - New and old perspectives on acute renal failure.
AB  - The pathophysiology, course, and treatment of acute renal failure in humans
      differs substantially from the ischemia/reflow model of renal injury commonly
      studied in rats and mice. Acute renal failure in humans is best understood as the
      result of an exacerbation of the usual state of hypoxia in the renal medulla and
      medullary rays, leading to reversible tubular dysfunction and glomerular
      vasoconstriction. A secondary inflammatory cascade may also play an important
      role, though this has not yet been clearly shown in patients.

PMID- 11975790
TI  - Argatroban: a direct thrombin inhibitor for heparin-induced thrombocytopenia and
      other clinical applications.
AB  - Argatroban, a direct thrombin inhibitor derived from arginine, is an effective
      anticoagulant indicated for prophylaxis or treatment of thrombosis in patients
      with heparin-induced thrombocytopenia (HIT). Argatroban has been used as an
      alternative anticoagulant in patients with HIT in various clinical conditions
      including interventional cardiovascular procedures that require anticoagulation.
      Satisfactory clinical outcomes with acceptable complications have been reported
      in these patients. Whether argatroban offers additional clinical advantage over
      conventional heparin therapy in patients without HIT remains unclear. Argatroban
      has been evaluated as an alternative anticoagulant to replace heparin in various
      clinical studies, especially in patients with coronary artery disease or cerebral
      vascular disease. To date, it remains unclear if argatroban is more effective
      than heparin, although the agent seems to cause less bleeding complications. This
      article reviews the pharmacology of argatroban and its clinical application
      beyond the management of HIT, with particular emphasis on interventional
      cardiology procedure, acute myocardial infarction, unstable angina pectoris,
      cerebral thrombosis or ischemic stroke, peripheral obstructive arterial disease,
      and extracorporeal circulation.

PMID- 11975793
TI  - Progression of chronic renal disease.
AB  - Progressive chronic renal disease is characterized histologically by the
      accumulation of extracellular matrix proteins within the renal interstitium and
      progressive tubular atrophy. A number of kidney diseases and their progression to
      end-stage renal failure are driven by the intercrine, autocrine, paracrine, and
      endocrine effects of angiotensin II. Growth factors appear to have an important
      role in the development and progression of diabetic nephropathy. Substantial
      evidence indicates that induction of transforming growth factor beta (TGF-beta)
      is mediated by high levels of glucose. TGF-beta is pivotal for the hypertrophy of
      mesangial and tubular cells. Other factors such as hypertension, protein
      glycation products, and other mediators may further amplify the synthesis of TGF
      beta and/or the expression of its receptors in the diabetic state. Other
      cytokines, such as tumor necrosis factor alpha also contribute to the progression
      of chronic renal disease. The overall picture derived from several studies of
      chronic renal disease suggests that treatment of the progression of the renal
      fibrosis may require the use of several strategies to prevent the advent of end
      stage renal disease.

PMID- 11975794
TI  - Water-losing and water-retaining states: role of water channels and vasopressin
      receptor antagonists.
AB  - Alterations in water metabolism are present in conditions such as diabetes
      insipidus, syndrome of inappropriate antidiuretic hormone secretion, cardiac
      failure, cirrhosis, and pregnancy. Recent advances in molecular biology have
      enhanced our understanding of disordered water metabolism in these conditions.
      This review examines the roles of central vasopressin synthesis and release and
      collecting duct vasopressin V2 receptor and aquaporin-2 water channel regulation
      in water-losing and water-retaining states.

PMID- 11975795
TI  - Alternative approaches to the medical management of cardiovascular disease:
      acupuncture, electrical nerve, and spinal cord stimulation.

PMID- 11975796
TI  - Long-term clinical outcome of rescue balloon angioplasty compared with rescue
      stenting after failed thrombolysis.
AB  - Failed thrombolysis following acute myocardial infarction is associated with a
      poor prognosis. Balloon angioplasty with or without stenting is an established
      procedure in acute myocardial infarction and for failed thrombolysis (rescue
      percutaneous transluminal coronary angioplasty [PTCA]). Intracoronary stenting
      improves initial success rates, decreases incidence of abrupt closure, and
      reduces the rate of restenosis after angioplasty. The purpose of this study was
      to compare the effect of rescue PTCA with rescue stenting in the treatment of
      acute myocardial infarction after failed thrombolysis. Clinical data are from a
      retrospective review of 102 patients requiring rescue balloon angioplasty or
      stenting after failed thrombolysis for acute myocardial infarction. There was a
      greater incidence of recurrent angina in 11 patients (22%) in the rescue PTCA
      group versus 2 patients (4%) in the rescue stenting group. The in-hospital
      recurrent myocardial infarction rate was 14% in the rescue PTCA group versus 2%
      in the stented group. In the rescue PTCA cohort, 11 patients (22%) required in
      hospital repeat revascularization versus 2 patients in the stented group. The in
      hospital mortality rate was higher in the PTCA group (10%) versus that in the
      stent group (2%). There was no significant difference in the incidence of
      postdischarge deaths. Rescue stenting is superior to rescue angioplasty. The
      procedure is associated with lower in-hospital angina and recurrent myocardial
      infarction, and the need for fewer repeat revascularizations. Long-term patients
      treated with stents required fewer revascularization procedures. Overall, rescue
      stenting was associated with a significantly lower mortality.

PMID- 11975797
TI  - Ticlopidine-associated thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura is a rare complication of ticlopidine
      treatment. This syndrome has been reported to occur typically within the first
      few weeks after the initiation of therapy. The authors describe a case of a 72
      year-old woman in whom thrombotic thrombocytopenic purpura developed just 2 days
      after starting ticlopidine therapy for a new-onset ischemic stroke. The patient
      responded successfully to plasmapheresis. The authors are reporting this case to
      emphasize the unpredictable nature of the association between the drug and the
      disease, which necessitates careful hematologic monitoring.

PMID- 11975798
TI  - Emerging indications for cardiac pacing.
AB  - Substantial data have been accumulated and indications have been well delineated
      for pacemaker implantation in the treatment of sinus node dysfunction and heart
      block. However, many other indications have been proposed for pacemaker
      implantation. In this review, the authors examine available data regarding
      pacemaker implantation for new indications: neurally mediated syncope,
      hypertrophic obstructive cardiomyopathy, congestive heart failure, prevention of
      atrial fibrillation, and the relative merits of single-chamber and dual-chamber
      pacemakers.

PMID- 11975799
TI  - Chronic mesenteric ischemia: diagnosis and treatment.
AB  - Chronic mesenteric ischemia is an uncommon manifestation of atherosclerotic
      disease. The presentation of chronic mesenteric ischemia is often confusing and
      the diagnosis is usually not made until late in the course of the disease.
      Selective angiography is considered the gold standard for establishing the
      diagnosis of chronic mesenteric ischemia. The treatment options for patients
      presenting with symptomatic chronic mesenteric ischemia include various surgical
      approaches to revascularization and catheter-based interventions.

PMID- 11975800
TI  - Alternative approaches to the medical management of angina pectoris: acupuncture,
      electrical nerve stimulation, and spinal cord stimulation.
AB  - Complementary or alternative modalities of medical treatment have been gaining
      attention as primary or supplementary therapies in cardiovascular disease pain
      management. However, definitive research in these areas has been limited by the
      inability to perform placebo-controlled trials when evaluating these treatments.
      Preliminary studies have suggested a possible benefit from acupuncture,
      electrical nerve stimulation, and spinal cord stimulation in the treatment of
      patients with angina pectoris and coronary artery disease.

PMID- 11975801
TI  - Vascular access problems in dialysis patients: pathogenesis and strategies for
      management.
AB  - Repetitive hemodialysis was made possible through the development of a chronic
      means of accessing the circulation. This was accomplished through the use of
      arteriovenous fistulae or grafts, using autologous veins or synthetic materials.
      Although the arteriovenous fistula remains the access of choice, synthetic
      arteriovenous grafts are used in most patients because of problems with late
      referral to a nephrologist and poor vasculature. This article describes the means
      of accessing the circulation for hemodialysis, the pathogenesis of access failure
      through progressive stenosis followed by thrombosis, methods of detecting access
      dysfunction before thrombosis, and therapeutic options. Although angiographic or
      surgical intervention remain the mainstays of management, medical treatments to
      decrease stenosis and delay thrombosis are currently under investigation.

PMID- 11975802
TI  - Cardiac drug and psychotropic drug interactions: significance and
      recommendations.
AB  - Understanding cardiac drug interactions with concurrent psychotropic
      prescriptions is essential for the practicing cardiologist, primary care
      physician, and psychiatrist. There has been an explosion in the use of new drugs
      in both psychiatry and cardiology without widespread knowledge of their potential
      interactions. The increasing tendency toward polypharmacy, the use of
      psychotropic medications by cardiologists and primary care physicians caring for
      cardiac patients, and the growth of the aging population present major challenges
      for the practitioner. Finally, there is a need to have models and paradigms for
      predicting potential drug interactions-the cytochrome P450 schema. This article
      describes a method to identify, understand, and codify the interactions between
      psychotropic and cardiac drugs, a systematic approach for updating this key
      database, and specific cardiac-psychotropic drug interactions. Specifically, this
      paper 1) details the interactions, 2) addresses the level of their clinical
      significance, 3) describes the potential mechanism(s) of the interactions, and 4)
      offers recommendations to the clinician (Appendix). Because the majority of the
      original clinical trials, either for cardiac medications or for psychotropic
      drugs, did not include studies comparing these two drug domains
      contemporaneously, their interactions often become known only with their combined
      use in the clinical arena, using the patient as "guinea pig" and through
      subsequent reporting.

PMID- 11975803
TI  - Ranolazine: a potential new treatment for chronic stable angina.
AB  - Ranolazine is a novel antianginal agent currently under investigation as
      monotherapy and adjunct therapy for the treatment of chronic stable angina.
      Although the mechanism of action of ranolazine is not completely understood, it
      is believed to involve a reduction in fatty acid oxidation, ultimately leading to
      a shift in myocardial energy production from fatty acid oxidation to glucose
      oxidation. Because the oxidation of glucose requires less oxygen than the
      oxidation of fatty acids, ranolazine can help maintain myocardial function in
      times of ischemia. In addition, ranolazine does not significantly affect blood
      pressure, heart rate, or cardiac conduction. The clinical data with ranolazine
      focuses on its use in chronic stable angina, where it has been shown to increase
      exercise tolerance and decrease angina compared with placebo and in combination
      with beta-blockers and calcium-channel blockers. The use of ranolazine for other
      cardiac conditions and the effect of ranolazine on morbidity and mortality remain
      to be determined.

PMID- 11975804
TI  - Why do we reject grafts?
AB  - One of the puzzles in clinical and experimental organ and tissue transplantation
      has been why it is that, with the exception of transplantation between
      genetically identical twin pairs, transplantation results in a rapidly
      progressing immune response to the point of tissue necrosis in a matter of a few
      days, even though the recipient has not been immunized to the donor. Indeed, the
      numbers of T lymphocytes predetermined to react against grafts are relatively
      abundant compared to those that recognize microbial antigens. Cellular,
      molecular, and genetic studies are now revealing the nature of T-cell
      recognition, and why it is that we cannot freely exchange tissue grafts.

PMID- 11975805
TI  - Glomerular therapeutics: looking back, looking forward.
AB  - Fifty years ago, the prospects for treatment of glomerulonephritis were dim.
      Beginning around 1950 the field of "glomerular therapeutics" was begun by the
      introduction of new agents (adrenocorticotrophic hormone, cortisone, nitrogen
      mustard) as possible disease-modifying therapies for the various forms of
      glomerular disease. For the next several decades these and other agents
      (azathioprine, cyclophosphamide, chlorambucil, prednisone) were used
      therapeutically in a largely uncontrolled and anecdotal fashion. The application
      of randomized, controlled trials led to the adoption of some forms of therapy as
      both effective and reasonably safe, and the rejection of others as either
      ineffective or hazardous. New regimens involving different routes of
      administration or dosing schedules were adopted. After about another two decades,
      new and increasingly selective agents began to be introduced into the therapeutic
      armamentarium (cyclosporine, mycophenolate mofetil). Diseases previously
      associated with a very poor outcome were transformed into manageable disorders.
      The consequences of glomerular disease (e.g., nephrotic syndrome, chronic renal
      failure) were now subject to control and alleviation in many circumstances. The
      next transformation of "glomerular therapeutics" is now under way. The revolution
      in molecular genetics and pharmacogenomics will allow new agents to be developed
      that target specific aspects of the pathogenic mechanisms underlying glomerular
      disease. This transformation will not be an easy one, because development,
      testing, approval, and application of these new concepts in therapeutics (e.g.,
      somatic gene therapy) will be time consuming and expensive. Eventually, the
      understanding of the genetic basis of susceptibility to glomerular disease and
      its progression will allow a preventative and curative, rather than palliative,
      strategy to emerge.

PMID- 11975806
TI  - Does metformin provide a new approach to the management of obesity?

PMID- 11975807
TI  - Metformin and carbohydrate-modified diet: a novel obesity treatment protocol:
      preliminary findings from a case series of nondiabetic women with midlife weight
      gain and hyperinsulinemia.
AB  - The authors conducted a retrospective analysis of a new obesity treatment
      protocol, metformin and hypocaloric, carbohydrate-modified diet, in high-risk,
      nondiabetic hyperinsulinemic women with progressive midlife weight gain
      (refractory to diet and exercise). Thirty consecutive nondiabetic women with
      glucose-mediated area-under-the-curve (AUC) insulin elevations (>or=100
      microU/mL) in two body mass index (BMI) categories (group I: 25 to 32.9 kg/m(2)
      and group II: 33 to 41.7 kg/m(2)) participated in a 1-year treatment program of
      metformin (mean daily doses of 1,500 mg/day [group I] and 2,000 mg/day [group
      II]) and carbohydrate-modified dietary regimens. Follow-up body weight (at 3, 6,
      and 12 months), percentage of patients meeting goal weight attainment (10%
      reduction in body weight or BMI normalization), and fasting insulin levels (as
      available) are reported in 26 women (18/18 in group I and 8/12 in group II) who
      returned for one or more follow-up visits. Significant weight loss was observed
      at 3, 6, and 12 months in both group I (3.47 [SE 0.68], 6.41 [0.72], and 8.06
      [0.96] kg, P < 0.0001) and group II (4.4 [0.8], 9.7 [2.3], 15.1 [3.3], P = 0.001,
      0.004, 0.011). Twenty-five of 26 (96%) patients lost >or=5% of their body weight
      at 6 months and 21/26 (81%) patients lost >or=10% of their body weight at 12
      months. Posttreatment fasting insulin decrement (-35.5 [8.2]%) was the most
      significant predictor of 1-year weight loss (R(2)=0.656, regression coefficient =
      0.810, P = 0.005). Following completion of the 1-year intervention study, weight
      stabilization (within 1 kg) was observed at a 6-month surveillance in 8/9
      patients who attained goal weight and continued metformin without additional
      nutritional counseling, in contrast to weight gain (>or=4 kg or 50% of lost
      weight) in 5/6 patients who discontinued metformin. The authors concluded that
      metformin and carbohydrate-modified hypocaloric diet could be an effective novel
      treatment for long-term weight management in nondiabetic, hyperinsulinemic women.

PMID- 11975808
TI  - Ethanol does not exert myocardial preconditioning in an intact rabbit model of
      ischemia/reperfusion.
AB  - Some epidemiologic analyses suggest that moderate drinking of alcohol may have
      beneficial effects on the heart. An experimental in vitro study also indicated
      that acute alcohol administration may precondition myocardium against ischemia,
      but only if it is washed out before ischemia. The goal of this study was to test
      whether alcohol + washout preconditions the myocardium to ischemia, reducing
      necrosis after ischemia/reperfusion in an in vivo model. Two groups of
      anesthetized open-chest rabbits received ethanol (0.5 mL/kg, intravenously) at 90
      minutes before (Group 1, alcohol preconditioning, n = 8) or 5 minutes before
      (Group 2, acute, n = 8) coronary artery occlusion (CAO); control rabbits received
      saline (Group 3, n = 8). All rabbits received 30 minutes of CAO and 3 hours of
      reperfusion. Blood alcohol level at the time of CAO in Group 1 had returned to
      control level (< 10 mg/dL). Alcohol level in Group 2 was 162 +/- 9 mg/dL. There
      were no differences in hemodynamics, ischemic risk region size, or collateral
      blood flow among groups. Alcohol, with or without washout, failed to reduce
      necrosis. Infarct size (% risk region) was 45 +/- 5% in control rabbits, 48 +/-
      6% with acute administration, and 53 +/- 7% with washout (P = 0.57). These data
      indicate that alcohol + washout did not precondition hearts against ischemia in
      this model, adding evidence to the theory that acute alcohol administration has
      no direct beneficial effect on ischemic myocardium.

PMID- 11975809
TI  - Serum neopterin and activity of coronary artery disease.
AB  - Inflammation plays a key role in the pathogenesis of atherosclerosis. In coronary
      artery disease (CAD), the release of different cytokines activates cellular
      defense. Infiltration of neutrophils and monocytes/macrophages is detected in the
      vessel wall in patients with CAD. Macrophages activated by interferon gamma
      synthesize metalloproteinases and neopterin, a pteridin derivative that has been
      used as an immune marker. To determine neopterin levels in patients with chronic
      CAD and acute coronary syndromes, the authors studied 116 subjects: 1) 25
      consecutive patients (18 men, 7 women; mean age 68.5 +/- 14.3, range 40 to 86
      years) with unstable angina or acute myocardial infarction (AMI); 2) 31
      consecutive patients (25 men, 6 women; mean age 64 +/- 12.7, range 47 to 83
      years) with signs and symptoms of clinically stable CAD; and 3) 60 consecutive
      healthy blood donors (38 men, 22 women; mean age 54.4 +/- 6.23, range 44 to 66
      years). Neopterin levels were determined with a commercially available enzyme
      linked immunosorbent assay method. In patients with unstable angina and AMI
      before thrombolytic therapy, neopterin levels were not significantly different
      from levels in patients with stable CAD (5.97 +/- 1.4 versus 7.84 +/- 3.56
      nmol/L; P = 0.15). Neopterin levels in both patient groups did not significantly
      differ from levels in control subjects (P > 0.1). Neopterin levels in patients
      with unstable angina and AMI were measured four times during a 72-hour period.
      The lowest value was observed at baseline and differed significantly from values
      after 72 hours (P < 0.001; 5.97 +/- 1.4 versus 9.25 +/- 2.36). Neopterin levels
      after 72 hours were also significantly different from initial values in patients
      with stable CAD (P < 0.001). There was no correlation between neopterin and
      creatine kinase (CK) levels, CK-MB isoenzyme, or troponin I as markers for the
      extent of the myocardial injury during the observation period. These data do not
      support previous reports of higher baseline levels of serum neopterin in patients
      with unstable angina or AMI compared with patients with chronic, stable CAD and
      healthy controls. Neopterin as a marker of macrophage activation is significantly
      increased in patients with AMI and unstable angina shortly after the onset of
      symptoms (after a period of 72 hours), supporting the hypothesis of monocyte and
      macrophage activation in patients with an acute coronary syndrome or AMI.

PMID- 11975810
TI  - Probable Kawasaki disease in a 52-year-old man presenting with acute myocardial
      infarction treated with percutaneous revascularization.
AB  - This is a case report of a 52-year-old man who presented with an acute myocardial
      infarction. In the process of performing an angiogram to delineate the anatomy
      for possible percutaneous transluminal coronary angioplasty, large, diffuse
      coronary aneurysms were observed. When the vessel was opened, several aneurysms
      were seen to contain thrombus. The size, location, and diffuseness of the
      aneurysms are suggestive of Kawasaki disease.

PMID- 11975811
TI  - Exercise update 2001.
AB  - Recent studies addressing the role of exercise in the detection, prevention, and
      treatment of coronary heart disease have significantly expanded our knowledge
      base in this area. This therapeutic review is focused on physiologic parameters
      in exercise, electrocardiogram testing, and the preventive impact of low
      intensity regular exercise and the role of exercise training in selected patient
      populations.

PMID- 11975812
TI  - Inhibition of myocardial apoptosis as a therapeutic target in cardiovascular
      disease prevention: focus on caspase inhibition.
AB  - Apoptosis is a type of programmed cell death that is evident during embryonic
      development and normal tissue turnover. When the apoptotic activity extends
      beyond physiologic limits, it can determine and/or contribute to those pathologic
      states characterized by excessive cell loss and impairment of organ function. The
      clinical development of caspase inhibitors may represent a potential therapeutic
      strategy for influencing the onset and progression of ventricular dysfunction to
      terminal failure. This article focuses on the caspase cascade, a fundamental
      enzymatic system for apoptotic cell death. Caspases do not constitute the death
      signals, but are implicated in their transmission. These cytoplasmic cysteine
      proteases have a dual role in apoptosis. Caspases can operate as initiators,
      activating an endonuclease that catalyzes deoxyribonucleic acid fragmentation.
      Alternatively, caspases can act as effectors, participating in the total
      disassembly of cell structures. For example, apoptosis represents the principal
      form of myocyte death in the region of an acute myocardial infarction. In
      addition, apoptosis in the region bordering the infarct can influence the
      development of ischemic cardiomyopathy and ventricular dilation.

PMID- 11975813
TI  - The role of tumor necrosis factor in cardiac disease.
AB  - Tumor necrosis factor (TNF) is a proinflammatory cytokine that can produce
      widespread deleterious effects when expressed in large amounts. It is produced in
      the heart by both cardiac myocytes and resident macrophages under conditions of
      cardiac stress, and is thought to be responsible for many of the untoward
      manifestations of cardiac disease. This article discusses the role of TNF in
      heart disease and some potential therapeutic modalities that can influence the
      cytokine activity. The results of controlled studies would suggest that TNF
      inhibition does not influence the clinical course of patients with heart failure.

PMID- 11975815
TI  - Bradykinin for the treatment of cardiovascular disease.
AB  - Bradykinin is a vasoactive kinin known to be involved in many biologic processes.
      Levels of bradykinin have been shown to be elevated in a number of cardiac
      diseases. It is thought that these elevated levels play a protective role in
      cardiovascular diseases. Preliminary studies have demonstrated that bradykinin
      may have beneficial effects on a wide spectrum of cardiovascular disorders.
      Though much study is still required, bradykinin augmentation represents an
      exciting new target for the treatment of cardiovascular disease.

PMID- 11975814
TI  - Systemic inflammation as a cardiovascular disease risk factor and as a potential
      target for drug therapy.
AB  - Inflammation-related processes play a key role the current etiologic model of
      atherosclerosis and its acute complications. Recent evidence suggests that blood
      based biomarkers that reflect systemic inflammation may contribute to our ability
      to predict future risk of cardiovascular disease. Global markers of inflammation,
      such as C-reactive protein and fibrinogen, have been well studied as potential
      cardiovascular risk factors. A variety of additional markers that reflect various
      elements of the complex systems governing inflammation, including proinflammatory
      and antiinflammatory cytokines, mediators of cellular adhesion, and matrix
      degradation enzymes, are also worthy of study. Although many previous studies
      have examined the relation of inflammation to myocardial infarction, emerging
      evidence suggests that other cardiovascular phenotypes such as ischemic stroke
      and early-stage atherosclerosis may also be related to inflammation. Further
      elucidating the role of inflammation in cardiovascular disease may lead to the
      identification of new targets for preventive or therapeutic interventions. In
      addition, markers of inflammation may be useful as a means to predict or monitor
      an individual's response to currently available cardiovascular therapies, such as
      aspirin or HMG coenzyme A reductase inhibitors, that may act via antiinflammatory
      mechanisms.

PMID- 11975817
TI  - beta3-Adrenergic receptor.

PMID- 11975816
TI  - Aggrenox: an aspirin and extended-release dipyridamole combination.
AB  - Stroke is one of the leading causes of death in the United States. The risk of
      experiencing a recurrent stroke remains elevated for several years after an
      initial stroke or a transient ischemic attack (TIA), therefore secondary
      prevention is crucial in reducing the risk of stroke and the complications and
      costs associated with stroke. Aggrenox, a combination of low-dose aspirin and
      extended-release dipyridamole, is a new agent that is effective in the secondary
      prevention of stroke and transient ischemia of the brain. The clinical effect of
      its two antiplatelet agents are additive and significantly better than either
      aspirin or dipyridamole alone, although it has not been shown to be more
      effective than aspirin alone in preventing death. Aggrenox is much more expensive
      than aspirin alone but has been shown to be more cost-effective. At this point,
      much of the pharmacologic information concerning this combination agent is based
      on previous data about aspirin and immediate-release dipyridamole. This
      combination of aspirin and extended-release dipyridamole may play a significant
      role in secondary stroke and TIA prevention.

PMID- 11975818
TI  - Combination therapy for maximal myocardial infarct size reduction.
AB  - The aim of this study was to test whether myocardial infarct size reduction would
      be optimized by combining three known effective therapies: cariporide, regional
      hypothermia, and ischemic preconditioning (CHIP). Before coronary artery
      occlusion (CAO), treated rabbits (CHIP, n = 7) received cariporide (0.3 mg/kg),
      ischemic preconditioning (7 minutes ischemia and 5 minutes reperfusion), then 20
      minutes of mild regional hypothermia (34 degrees C). Control rabbits (n = 7)
      received saline and a 34-minute waiting period. All received 30 minutes of CAO
      and reperfusion. In another study, rabbits (n = 8 in each group) received 90
      minutes of CAO. In the 30-minute protocol, the authors found that hearts in both
      groups were equally ischemic during CAO. Mean ischemic risk zones were similar in
      both groups; however, in CHIP hearts, infarct size was 4 +/- 1% of risk zone, a
      reduction of 91% compared with control rabbits (44 +/- 7% of the risk zone, P =
      0.001). In the 90-minute protocol, risk zone size was similar in both groups, but
      infarct size in control hearts was 76 +/- 3% of the risk zone compared with 34 +/
      7% in CHIP treated hearts (P = 0.0003). In summary, the combined treatment
      provided extraordinary protection. Infarct comprised only 4% of the risk region
      after 30-minute ischemia-a far greater reduction than was previously observed in
      the same laboratory using any single intervention. After 90 minutes of ischemia,
      infarct was 55% lower in CHIP hearts, suggesting that this therapeutic approach
      dramatically reduces ischemia/reperfusion cell death, even during long
      occlusions.

PMID- 11975819
TI  - Intraoral chilling versus oral sumatriptan for acute migraine.
AB  - Migraine pathophysiology is associated with a dural inflammation. Recent evidence
      suggests that the primary inflammation occurs in a maxillary nerve segment,
      accessible intraorally. Local tenderness, related to symptom laterality, has been
      palpated consistently in asymptomatic migraine patients, and significant migraine
      relief has been obtained from chilling confined to this area. Thirty-five
      symptomatic episodic migraine patients were enrolled in this study, comparing 40
      minutes of bilateral intraoral chilling, 50 mg of oral sumatriptan, and 40
      minutes of sham (tongue) chilling. Hollow metal tubes chilled by circulating ice
      water were held in the maxillary molar periapical areas by the patient. Pain and
      nausea were recorded at baseline and 1, 2, 4, and 24 hours after start of
      treatment, using a numeric symptom-relief scale. Significant mean headache relief
      was obtained by maxillary chilling and sumatriptan at all four time intervals,
      with poor relief obtained by placebo. Maxillary chilling was more effective than
      sumatriptan at all four time intervals. Significant nausea relief was obtained by
      maxillary chilling and sumatriptan at posttreatment and 2 and 4 hours later. At
      24 hours, some headache and nausea recurrence was noted with sumatriptan. The
      repeated-measures analysis of variance indicated that both treatments, drug (P =
      0.024) and maxillary chilling (P = 0.001), reduced the headache, as compared with
      the control group. Tenderness suggests local inflammation associated with
      vasodilatation and edema. Because chilling can resolve local edema, these
      findings raise the possibility that an intraoral inflammation may be a factor in
      migraine etiology.

PMID- 11975820
TI  - Repeated doses of tissue plasminogen activator for failed thrombolysis: case
      report and review of the literature.
AB  - This article reports the first case of a patient presenting with acute myocardial
      infarction in whom a repeated dose of tissue plasminogen activator (t-PA) was
      able to achieve successful thrombolysis after a first dose of t-PA itself failed
      to do so. This case report presents an alternative approach for the treatment of
      patients who fail thrombolysis after an initial dose of t-PA, an approach that
      might be particularly useful in hospitals that do not have immediate access to
      advanced interventional services.

PMID- 11975821
TI  - Tobacco smoking, nicotine, and nicotine and non-nicotine replacement therapies.
AB  - Tobacco smoking is associated with an increased risk for the development of
      coronary and pulmonary vascular diseases and smoking cessation will greatly
      reduce this risk. Nicotine replacement and nonnicotine modalities have been used
      alone and in combination to help in smoking cessation. These treatment modalities
      appear to be safe in patients with known stable coronary artery disease.

PMID- 11975822
TI  - Vasopeptidase inhibitors, neutral endopeptidase inhibitors, and dual inhibitors
      of angiotensin-converting enzyme and neutral endopeptidase.
AB  - Vasopeptidase inhibitors represent a new class of cardiovascular drugs. They
      function as a combined angiotensin-converting enzyme (ACE) inhibitor and neutral
      endopeptidase (NEP) inhibitor, the latter of which potentiates the actions of
      atrial natriuretic peptide (ANP) by minimizing its degradation in the
      circulation. The consequence of such dual inhibition is a synergistic reduction
      of vasoconstriction and enhancement of vasodilation, thereby serving to more
      effectively reduce blood pressure. Furthermore, inhibition of the renin
      angiotensin-aldosterone system (RAAS) prevents physiologic compensatory responses
      in vivo seen with NEP inhibition alone. Vasopeptidase inhibitors have also shown
      to potentiate bradykinin and adrenomedullin, which additionally contribute to
      cardiovascular regulation. The most extensively researched and promising agents
      within the class of VP inhibitors is omapatrilat, a mercaptoacyl derivative of a
      bicyclic thiazepinone dipeptide. It is a single molecule with equal potency and
      affinity for ACE and NEP inhibition. Although ACE inhibition tends to more
      selectively benefit high-renin models of hypertension, vasopeptidase inhibition
      has been shown to be equally efficacious in low-, normal-, and high-renin models.
      Contrary to NEP inhibition alone, omapatrilat has also demonstrated the ability
      to significantly reduce blood pressure in spontaneously hypertensive rats, the
      equivalent of essential hypertension in humans. Studies also suggest that
      omapatrilat has cardioprotective properties, especially in the setting of
      congestive heart failure. More specifically, animal models have demonstrated
      omapatrilat to be more effective than ACE inhibition alone in remodeling the
      heart and improving its contractile function. Human studies have documented the
      efficacy of omapatrilat in the treatment of both hypertension and, to a lesser
      extent, heart failure. Safety concerns (specifically angioedema) are currently
      being addressed before the widespread utilization of this promising new agent.

PMID- 11975823
TI  - Cardiovascular considerations in using topical, oral, and intravenous drugs for
      the treatment of glaucoma and ocular hypertension: focus on beta-adrenergic
      blockade.
AB  - Glaucoma and ocular hypertension are highly prevalent conditions in individuals
      over the age of 40 and are commonly seen together in patients with cardiovascular
      disease. Many of the antiglaucoma medications, when systemically absorbed, affect
      the sympathetic and parasympathetic nervous systems of patients and can cause
      cardiovascular toxicity. Such adverse effects are frequently associated with the
      long-term use of potentially toxic agents in elderly people, who are most prone
      to chronic eye disease. Moreover, patients may not associate their symptoms with
      the topical eye medications, and consequently may not report adverse drug
      effects. Drug-drug interactions can also occur when patients are taking
      medications for both cardiovascular disease and glaucoma. This review focuses on
      beta-adrenergic blockers as topical antiglaucoma medications and other topical
      antiglaucoma drugs. The systemic toxicity of these agents is reviewed, along with
      the possible drug interactions. Brief mention is also made of other antiglaucoma
      medications used alone and in combination with topical beta-blockers.

PMID- 11975824
TI  - Lercanidipine: a novel dihydropyridine calcium-channel blocker.
AB  - Calcium-channel blockers (CCBs) have been used for the treatment of hypertension
      for more than 20 years, and recent clinical trials support the efficacy and
      safety of long-acting dihydropyridine (DHP) CCBs for a wide spectrum of
      hypertensive patients, including diabetic hypertensive patients. DHP CCBs are
      effective agents overall and are particularly effective when used in combination
      with other agents. Lercanidipine is a novel DHP CCB effective for the treatment
      of mild-to-moderate hypertension. Compared with other DHP CCBs, lercanidipine has
      a molecular design that imparts greater solubility within the arterial cellular
      membrane bilayer, membrane-controlled kinetics, and a high cholesterol tolerance
      factor. These favorable membrane-controlled kinetics impart a gradual onset of
      vasodilation and a long duration of action. Further, the unique pharmacokinetic
      and pharmacodynamic properties of lercanidipine appear to contribute to its
      efficacy and favorable safety profile. In clinical trials in the treatment of
      mild-to-moderate hypertension, lercanidipine was administered at a starting dose
      of 10 mg once daily, and increased to 20 mg once daily for nonresponders. Studies
      have shown that lercanidipine has a 24-hour antihypertensive effect and causes no
      significant increase in heart rate. Lercanidipine has been shown to be effective
      in a wide range of hypertensive patients, including mild-to-moderate
      hypertension, severe hypertension, the elderly, and those with isolated systolic
      hypertension. It is associated with a low rate of adverse events. Because of its
      efficacy and favorable safety profile, lercanidipine has the potential to improve
      blood pressure control in a wide range of patients, including those who have not
      responded to, or who have been unable to tolerate, other antihypertensive agents.

PMID- 11975826
TI  - Computer-enhanced frequency-domain and 12-lead electrocardiography accurately
      detect abnormalities consistent with obstructive and nonobstructive coronary
      artery disease.
AB  - Noninvasive methods of identifying coronary artery disease are not consistently
      accurate. To identify abnormalities associated with angiographically determined
      coronary artery disease, the authors sought to quantify the utility of a new
      device, a digital database-driven multiphase electrocardiograph system (3DMP),
      which produces a computer-enhanced frequency/time-domain resting
      electrocardiogram, in conjunction with a 12-lead electrocardiogram. The authors
      compared resting 3DMP results from those of coronary angiograms to identify
      abnormalities associated with coronary artery disease in a random sample of 136
      patients. Using a discrete-Fourier transform signal-averaging variant and a
      series of mathematic transformations, the computer-expert system analyzed signals
      in the 0.1- to 50-Hz range. The system identified abnormalities by comparing
      results with a 21,000-patient database culled from predicate research. The system
      detected abnormalities in 96.0% of patients subsequently found to have 70% or
      greater stenosis by angiography. For patients with a 40% or less times a more
      than 50% occlusion, the system detected abnormalities in 75% of cases. For
      patients with a 50% or less times a 70% or less occlusion, it detected
      abnormalities in 90% of cases. Overall sensitivity for the study was 93.3%
      (positive predictive value, 91.2%; specificity, 83%; negative predictive value,
      86.7%). No gender differences were detected. A 3DMP electrocardiograph system
      combined with 12-lead electrocardiography appears to have measurable, diagnostic
      utility in identifying 3DMP abnormalities associated with coronary artery
      disease, and warrants further study.

PMID- 11975827
TI  - Exercise training improves diastolic perfusion time in patients with coronary
      artery disease.
AB  - Exercise training elicits an improvement in work capacity and in left-ventricular
      function in patients with coronary artery disease. An improvement in myocardial
      oxygen supply accounts for these effects. The aim of this study was to test the
      hypothesis that exercise training could favorably influence diastolic perfusion
      time, a major determinant of subendocardial perfusion. Twenty-two male patients
      with coronary artery disease were randomized to a training or control group. At
      the study entry and after one year, all patients underwent an exercise stress
      test. After one year, rest heart rate was lower and diastolic perfusion time was
      higher in the training group but not in the control group. At peak of exercise,
      diastolic perfusion time increased and ST-segment depression decreased
      significantly in the training group but not in the control group. A significant
      relation was found between the R-R interval and the diastolic perfusion time
      either before or after training, with a difference in the intercepts of two
      regressions. Training shifted updown-line regression, effecting a higher value of
      diastolic perfusion time for a given value of heart rate. Thus, training
      increases diastolic perfusion time, independently from the effect on heart rate.
      This mechanism may contribute to the improvement of myocardial perfusion.

PMID- 11975828
TI  - Neointima formation after stent implantation in an experimental model of
      restenosis: polytetrafluoroethylene-covered versus uncovered stainless steel
      stents.
AB  - The aim of the study was to assess whether stents covered with a membrane of
      polytetrafluoroethylene spanned over the mashes of a sandwich-configured double
      stent (n = 15) prevent migration of smooth muscle cells through stent spaces,
      leading to less neointima formation compared with uncovered stainless steel
      stents (n = 14) in iliac arteries of male Chinchilla Bastard rabbits (n = 18).
      Lumen stenosis was assessed by quantitative angiography immediately before the
      animals were killed 5 weeks after stent deployment. Neointima formation was
      quantified by histomorphometric analysis. There were large regional and
      individual differences in neointima formation, leading locally to a significantly
      higher degree of stenosis in covered stents (histologically, 76.0 +/- 13.7 vs.
      62.9 +/- 12.9%; angiographically, 33.5 +/- 21.1 vs. 7.8 +/- 8.8%) compared with
      uncovered stents, though mean neointimal and lumen area values were not
      significantly different. In conclusion, polytetrafluoroethylene-covered stents do
      not prevent neointima formation compared with uncovered stents. Although the
      membrane reduces local smooth muscle cell migration, the neointima hyperplasia at
      the proximal and distal ends of a covered stent stimulates migration along its
      longitudinal axis. In this stent-restenosis model, regional and individual
      proliferation processes and not the membrane-covering strut-to-strut distances
      determine lumen restenosis.

PMID- 11975829
TI  - Estrogen replacement therapy for cognitive benefits: viable treatment or
      forgettable "senior moment"?
AB  - The perceived benefits of estrogen on cognitive function are one of the few
      remaining potential roles for estrogen replacement therapy. The justification for
      such a role has a strong biologic basis and is easily shown in animal models.
      Purported benefits for estrogen on cognitive function include neuroprotective,
      neurostimulating, and neurotrophic effects. The objective of this study was to
      review the literature and to evaluate the role of estrogen replacement therapy in
      improving cognition in Alzheimer disease, vascular dementia, premenopausal women,
      and postmenopausal women without dementia. Additionally, the authors separately
      looked at the neuroprotective effects of estrogen replacement therapy on the
      subsequent risk of dementia. The available data fail to show a therapeutic
      benefit of estrogen replacement therapy in Alzheimer disease. Surprisingly,
      limited data allow consideration of a possible role of estrogen in the management
      of vascular dementia. Additionally, younger females with low estrogen levels
      secondary to primary ovarian failure and Turner syndrome benefit from estrogen
      replacement therapy. Despite the limited role of estrogen replacement therapy in
      cognitive enhancement, neuroprotective properties are likely because several
      prospective studies indicate a reduced risk of Alzheimer disease. A critical
      window of opportunity seems to exist for this protective effect in Alzheimer
      disease because once established, the course of the disease is not affected by
      concomitant estrogen replacement therapy. The authors conclude that the use of
      estrogen replacement therapy is not substantiated for the treatment of patients
      with Alzheimer disease. Alternatively, because of the evidence for a possible
      neuroprotective effect, women at high risk for the development of Alzheimer
      disease may be appropriate candidates for estrogen replacement therapy. Such a
      decision should be made on a case-by-case basis, after careful consideration of
      the risks and benefits.

PMID- 11975830
TI  - Orthostatic hypotension in pediatrics.
AB  - Transient orthostatic hypotension is a common experience of many healthy
      adolescents and is the expected outcome of relatively dilated-dependent vascular
      tone. These children may experience brief symptoms of orthostatic intolerance
      when standing up rapidly, but they have no chronic symptoms or diseases. However,
      persistent orthostatic hypotension and chronic symptoms of orthostatic
      intolerance indicate postural tachycardia syndrome.

PMID- 11975831
TI  - Neonatal and pediatric extracorporeal membrane oxygenation.
AB  - Extracorporeal membrane oxygenation provides an external circulation for the
      critically ill patient with components capable of supporting the
      cardiorespiratory system while the patient's innate organs recover from the
      primary insult. This therapy is often used in children with relatively well
      elucidated indications. Although initially used in the setting of neonatal
      respiratory failure, the use of extracorporeal membrane oxygenation for pediatric
      respiratory and cardiac indications is not uncommon. The complications and the
      outcomes of extracorporeal membrane oxygenation compare favorably with other
      forms of conventional therapy.

PMID- 11975832
TI  - Approach to the treatment of hypertension in children.
AB  - Childhood hypertension necessitates a careful approach to diagnosis and a
      tailored approach to management. Hypertension in children should not be
      considered a rare condition. The diagnosis of hypertension must be assessed
      carefully, with attention to age, sex, and height standards. Also, careful
      attention should be given to the methods used to measure blood pressure. Once the
      diagnosis is made and the underlying etiologies have been evaluated and managed
      as necessary, both nonpharmacologic and pharmacologic approaches to treatment
      have been used. Nonpharmacologic approaches, especially weight reduction and
      increased physical activity, are beneficial. If pharmacologic approaches are
      needed, the goal of therapy should be to reduce blood pressure below the 95th
      percentile in the easiest, most effective manner that causes the fewest side
      effects. Angiotensin-converting enzyme inhibitors, calcium-channel blockers,
      alpha and beta blockers, and diuretics have all been used in children. Newer
      antihypertensives, such as angiotensin receptor blockers, are now being tested.

PMID- 11975833
TI  - Closing ventricular septal defects in the cardiac catheterization laboratory.
AB  - Current results of transcatheter closure of ventricular septal defects using
      double-umbrella devices are promising. The ventricular septal defect may be
      congenital muscular, residual after surgical ventricular septal defect repair, or
      acquired after myocardial infarction. The procedure is successful in 88% of
      patients, and most patients experience a significant improvement in clinical
      status. Although adverse events frequently occur at the time of implantation,
      late events related to the device or procedures are rare.

PMID- 11975834
TI  - Eprosartan: an angiotensin-II receptor antagonist for the management of
      hypertension.
AB  - Eprosartan is a competitive angiotensin-II receptor antagonist with a high
      affinity for the angiotensin-II subtype 1 receptor. The drug has an elimination
      half-life of approximately 5 to 9 hours and duration of antihypertensive effect
      of up to 24 hours. The antihypertensive efficacy of eprosartan has been examined
      in a number of placebo-controlled, dose-finding, and comparative trials. Results
      of these clinical trials have consistently shown statistically significant
      differences in antihypertensive efficacy favoring eprosartan doses of 400 mg or
      greater per day over placebo. Eprosartan was also shown to be at least as
      effective as enalapril at lowering blood pressure in patients with mild to severe
      hypertension. The frequency of adverse events observed with eprosartan has been
      similar to that seen with placebo. In addition, there are no clinically
      significant drug interactions associated with eprosartan. Given the excellent
      tolerability and drug-interaction profiles of eprosartan, the use of this agent
      may help to improve patient compliance to a drug regimen. In addition, eprosartan
      may be particularly advantageous when used as a part of combination therapy for
      the management of hypertension.

PMID- 11975835
TI  - Positive airway pressure for the failing heart.

PMID- 11975836
TI  - Gene activity changes in ischemically preconditioned rabbit heart gene: discovery
      array study.
AB  - This study tested the hypothesis that classic ischemic preconditioning can cause
      changes in gene expression patterns in the rabbit heart, assessed by gene array
      technology. Open-chest rabbits were randomly assigned to sham-operated and
      ischemically preconditioned groups. The sham-operated group received 5 hours and
      20 minutes of no intervention, while the ischemically preconditioned group was
      subjected to two episodes of preconditioning ischemia (5 minutes each) separated
      by 5 minutes of reperfusion, followed by an additional 5 hours and 5 minutes of
      reperfusion. (33)P-labeled cDNA from the sham-operated hearts and the nonischemic
      and preconditioned areas of the ischemically preconditioned group was hybridized
      to filters spotted with 18,376 human cDNA clones. Altogether, 35 genes with
      significantly altered expression patterns were discovered. In the preconditioned
      area, genes for MAPKAP kinase 3 and cathepsin G were up-regulated. In the
      nonischemic area, genes for GTP exchange factor, Na(+), K(+)-ATPase, Zn finger
      protein 35, a representative of the CEA family, cytochrome c oxidase, mitogen
      responsive phosphoprotein, and Ran-binding protein were up-regulated. None of the
      identified genes had been previously reported to be involved in ischemic
      preconditioning.

PMID- 11975837
TI  - Medical resource use and costs of congestive heart failure after carvedilol use.
AB  - A retrospective cohort study based on claims and medical chart data was conducted
      to compare healthcare use and costs in congestive heart failure patients with and
      without carvedilol. Adult patients with a minimum of two claims with a valid
      congestive heart failure diagnosis from 1997 to 1999 were included. Patients
      receiving continuous carvedilol treatment for at least 4 months were considered
      study case patients. Case patients were matched based on age, gender, race, and
      concomitant medication. Healthcare use and costs were compared between the case
      and control groups. A total of 128 case and 147 control patients were identified.
      There were no significant differences in demographic characteristics, concomitant
      medication, or New York Heart Association classification between these two
      groups. Analysis of variance and chi-square analyses were conducted for
      continuous and categorical variables, respectively. Statistical adjustments were
      made using a multivariate model. Carvedilol had a significant economic reduction
      in the overall expenditures by approximately $14,530. Facility expenditures were
      approximately $9,000 lower for the carvedilol group than for the control group.
      Carvedilol-treated patients had less frequent hospital admissions and shorter
      lengths of stay compared with patients not receiving carvedilol. Congestive heart
      failure patients receiving carvedilol have significantly less healthcare use and
      costs than patients not receiving carvedilol.

PMID- 11975838
TI  - Syndrome W: a new model of hyperinsulinemia, hypertension and midlife weight gain
      in healthy women with normal glucose tolerance.
AB  - To characterize a new insulin resistance syndrome in euglycemic midlife women and
      the relationship of its features (including hypertension and dyslipidemia), with
      hyperinsulinemia (AUC insulin > or = 100 microU/mL), retrospective cohort
      analysis was conducted in 278 consecutive women who presented to a Menopausal
      Health Program. Of 67 women with midlife weight gain "greater than 20 pounds
      since their twenties" and body mass indices (BMIs) between 25 and 32 kg/m(2),
      none of the subjects met criteria for Type 2 diabetes, 5 women had impaired
      glucose tolerance, and 36 women were hyperinsulinemic. Hyperinsulinemia was a
      highly statistically significant determinant of hypertension, dyslipidemia, and
      truncal obesity (Odds Ratios 10.6, 4.0, and 13.7; P values < or = 0.0001, < or =
      0.007, and < or = 0.0001) in cross-tabulations. AUC insulin was the best
      predictor variable of hypertension and dyslipidemia in univariate and
      multivariate logistic regression models (univariate P values 0.0004 and 0.0088).
      After adjustment for BMI, age, and estrogen use, the final models, correctly
      classified, respectively, 74% and 69% of all cases in the dataset (model P
      values: < or = 0.0001 and < or = 0.0067) and AUC insulin had a log-linear (i.e.,
      dose-dependent) relationship with hypertension and dyslipidemia, which suggests
      causality. We propose that the constellation of symptoms that includes midlife
      weight gain, "waist-gain," hypertension, dyslipidemia, and appetite dysregulation
      in euglycemic women with hyperinsulinemia be titled Syndrome W and suggest that
      the highly statistically significant relationship of hyperinsulinemia with the
      characteristic features are evidence of a causal role for insulin in its
      etiology. The identification of Syndrome W before the onset of overt impaired
      glucose tolerance, diabetes, or manifestations of coronary artery disease could
      have important clinical and public health implications for midlife women.

PMID- 11975839
TI  - Cardiac amyloidosis: a case report and therapeutic implications.
AB  - Primary amyloidosis with cardiac involvement presenting as congestive heart
      failure (CHF) usually carries an unfavorable prognosis, with median survival of
      about 6 months. We are reporting a case of cardiac amyloidosis with an initial
      presentation of CHF in which the patient survived for more than 9 years. The
      prognosis most likely depends on the period of disease remission (i.e., negative
      serum and urine immunoelectrophoresis), which, in turn, depends on response to
      chemotherapy.

PMID- 11975840
TI  - Atrial fibrillation.
AB  - The prevalence and incidence of atrial fibrillation increase with age. Atrial
      fibrillation is associated with a higher incidence of coronary events, stroke,
      and mortality than sinus rhythm. A fast ventricular rate associated with atrial
      fibrillation may cause tachycardia-related cardiomyopathy. Management of atrial
      fibrillation includes treatment of underlying causes and precipitating factors.
      Immediate direct-current cardioversion should be performed in persons with atrial
      fibrillation associated with acute myocardial infarction, chest pain due to
      myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous
      beta-blockers, verapamil, or diltiazem may be used to immediately slow a fast
      ventricular rate associated with atrial fibrillation. An oral beta-blocker,
      verapamil, or diltiazem should be given to persons with atrial fibrillation if a
      rapid ventricular rate occurs a rest or during exercise despite digoxin.
      Amiodarone may be used in selected persons with symptomatic life-threatening
      atrial fibrillation refractory to other drug therapy. Nondrug therapies should be
      performed in persons with symptomatic atrial fibrillation in whom a rapid
      ventricular rate cannot be slowed by drug therapy. Paroxysmal atrial fibrillation
      associated with the tachycardia-bradycardia syndrome should be managed with a
      permanent pacemaker in combination with drugs. A permanent pacemaker should be
      implanted in persons with atrial fibrillation in whom symptoms such as dizziness
      or syncope associated with non-drug-induced ventricular pauses longer than 3
      seconds develop. Elective direct-current cardioversion has a higher success rate
      and a lower incidence of cardiac adverse effects than medical cardioversion in
      converting atrial fibrillation to sinus rhythm. Unless transesophageal
      echocardiography shows no thrombus in the left atrial appendage before
      cardioversion, oral warfarin should be given for 3 weeks before elective direct
      current or drug cardioversion of atrial fibrillation and continued for at least 4
      weeks after maintenance of sinus rhythm. Many cardiologists prefer the treatment
      strategy of ventricular rate control plus warfarin rather than to maintain sinus
      rhythm with antiarrhythmic drugs, especially in older patients. Digoxin should
      not be used in persons with paroxysmal atrial fibrillation. Patients with chronic
      or paroxysmal atrial fibrillation who are at high risk for stroke should be
      treated with long-term warfarin to achieve an International Normalized Ratio
      (INR) of 2.0 to 3.0. Persons with atrial fibrillation who are at low risk for
      stroke or who have contraindications to warfarin should receive 325 mg aspirin
      daily.

PMID- 11975842
TI  - Exercise as a treatment modality for congestive heart failure.
AB  - Chronic congestive heart failure is a clinical syndrome that affects nearly 5
      million people in the United States alone. Patients with this condition have
      symptoms of dyspnea and exertional fatigue that often limit their daily
      activities and decrease their quality of life. There has recently been a paradigm
      shift in the management of congestive heart failure. Current strategies are
      focusing on improving the central cardiopulmonary abnormalities, such as
      decreased ejection fraction and increased capillary wedge pressure, and
      interventions aimed at improving the numerous peripheral changes that occur with
      congestive heart failure. Exercise as a treatment modality has been shown to
      affect many of these peripheral changes, specifically abnormalities in the
      skeletal muscle, peripheral blood flow, and neurohormonal milieu, which improve
      with appropriate exercise regimes. Exercise also reduces the symptoms of
      exertional fatigue, improves quality of life, and increases survival. This
      article reviews the current experience with exercise and congestive heart failure
      and discusses strategies used to implement an exercise program for patients.

PMID- 11975841
TI  - Congestive heart failure and continuous positive airway pressure therapy: support
      of a new modality for improving the prognosis and survival of patients with
      advanced congestive heart failure.
AB  - Nasal continuous positive airway pressure therapy has recently been studied as a
      nonpharmacologic adjunct to congestive heart failure therapy. In patients with
      congestive heart failure, it was reported that continuous positive airway
      pressure therapy for the condition Cheyne-Stokes respiration with central sleep
      apnea led to long-term improvements in cardiac function and alleviation of heart
      failure symptoms. Cheyne-Stokes respiration with central sleep apnea is a
      frequent breathing disorder well described in patients with congestive heart
      failure, and is an associated risk factor for increased cardiovascular morbidity
      and mortality. These apneas cause an increase in sympathetic nervous system
      activity, which would maintain afterload at a high level or tend to increase it
      with time, leading to further compromise of ejection fraction. Continuous
      positive airway pressure appears to benefit the failing heart by increasing
      intrathoracic pressure, which is believed to cause an increase in cardiac output
      by decreasing the pressure gradient across the heart wall and allowing the left
      ventricular end diastolic volume to decrease, thereby reducing the afterload.
      This beneficial "resting" of the heart has been documented to increase left
      ventricular ejection fraction, increase cardiac index, improve inspiratory muscle
      strength, lower blood pressure and heart rate, decrease plasma and overnight
      urinary levels of norepinephrine, lower levels of atrial natriuretic peptide and
      endothelin-1, and increase heart rate variability. Other benefits include
      improvement in New York Heart Association functional class status and improvement
      in dyspnea.

PMID- 11975843
TI  - Postoperative atrial fibrillation.
AB  - Postoperative atrial fibrillation is associated with significant morbidity,
      longer hospital stay, and higher related costs. Although the etiologic mechanism
      of postoperative atrial fibrillation and its optimum method of prophylaxis or
      management are not well defined, progress has been made during the past decade.
      This review focused on recent findings leading to a better understanding of the
      mechanisms and management of atrial fibrillation after surgery and current
      approaches directed at prevention of thromboembolic sequelae. Because
      postoperative atrial fibrillation is a frequent complication, preoperative risk
      assessment algorithms are being proposed to minimize the number of patients in
      whom an intervention to prevent atrial fibrillation is undertaken, and thus,
      reduce toxicity due to antiarrhythmic drug therapy. Finally, current data suggest
      that once atrial fibrillation has occurred, a rate-control strategy during the
      first 8 to 12 hours is reasonable because 50% of those episodes will resolve
      during this period. Beyond this period, a more aggressive approach using class IC
      or III antiarrhythmic drugs will hopefully reduce the number of patients
      requiring anticoagulation and prolonged drug therapy.

PMID- 11975844
TI  - Lovastatin and extended-release niacin combination product: the first drug
      combination for the management of hyperlipidemia.
AB  - Advicor (lovastatin and extended-release niacin) is the first cholesterol
      lowering combination product to become available for the management of
      hyperlipidemia. Lovastatin significantly lowers low-density lipoprotein
      cholesterol, whereas niacin significantly lowers triglycerides and lipoprotein
      (a) and markedly increases high-density lipoprotein cholesterol. These effects
      are ideal for managing a variety of lipid disorders, including metabolic
      syndrome. Lovastatin and niacin reduce coronary heart disease mortality in
      primary and secondary prevention patients, respectively. The extended-release
      niacin component uses a unique technology to minimize adverse effects (e.g.,
      flushing and hepatotoxicity) while retaining the same lipid-altering effects as
      immediate-release niacin. The combination product appears to be well tolerated,
      with discontinuation due to adverse effects other than flushing occurring in a
      similar percent of patients as for lovastatin in clinical trials. Approximately
      9% of patients discontinued the combination product due to flush. No confined
      cases of myopathy or hepatotoxicity have been reported with this product. Once
      daily dosing provides ease of administration that should improve compliance and
      result in a greater proportion of patients meeting their low-density lipoprotein
      cholesterol goals. The nomenclature surrounding niacin products used to treat
      dyslipidemias is confusing. While only two types of niacin formulations exist
      (immediate-release formulations and formulations which dissolve more slowly than
      immediate-release formulations), government regulations allow for slowly
      dissolved niacin formulations to be divided into two types of niacin products;
      those that are available over-the-counter (OTC) and those that are available by
      prescription only. Over-the-counter slowly dissolved niacin preparations are not
      classified as OTC per se, but are considered "nutritional supplements". For this
      reason, they fall under the jurisdiction of the Federal Trade Commission and do
      not fall under the umbrella of the FDA branch that controls dyslipidemic products
      (Endocrine and Metabolic Division of the Center for Drug Evaluation and
      Research). The slowly dissolved niacin nutritional supplements have not been
      reviewed by the FDA for safety nor efficacy in the treatment of dyslipidemia nor
      are they required to meet generic drug rules (even though various brands are
      available). These brands are described on their labels as "sustained-release",
      "timed-release", and "slow-release" for example. Only two slowly absorbed niacin
      products have been approved by the FDA for the treatment of dyslipidemia; they
      are Niaspan (Kos Pharmaceuticals, Inc., Miami, FL) and Advicor (Kos
      Pharmaceuticals, Inc., Miami, FL). The term "extended-release" has been given to
      these two products to simplify the terminology and differentiate the products
      from immediate-release niacin. In this review, we will use "extended-release" to
      refer to the FDA approved slowly dissolving niacin preparation and "sustained
      release" to refer to the nutritional supplements (not FDA approved).

PMID- 11975845
TI  - Optimizing prostate cancer suicide gene therapy using herpes simplex virus
      thymidine kinase active site variants.
AB  - The herpes simplex virus (HSV) thymidine kinase gene (tk) forms the basis of a
      widely used strategy for suicide gene therapy. A library of HSV thymidine kinase
      enzyme (TK) active site mutants having different affinities for guanosine analog
      prodrugs was developed. We sought to determine the optimal combination of tk
      variant and prodrug specifically for prostate cancer gene therapy, using in vitro
      and in vivo studies of adenovirally infected CL1, DU-145, and LNCaP tumor lines
      carrying wild-type tk, tk30, tk75, and sr39tk mutants expressed by a strong,
      constitutive cytomegalovirus promoter and treated with ganciclovir and acyclovir.
      In vitro experiments involving prostate cancer (CaP) cell line infection were
      carried out with a broad range of prodrug concentrations, and cell killing was
      determined by limiting dilution (colony-forming), MTT, and propidium iodide
      assays. In vivo studies based on CL1-GFP xenograft experiments were carried out
      to examine the ability of each TK variant to prevent tumor formation and to
      inhibit tumor growth and development of metastases in established orthotopic and
      subcutaneous tumors in SCID mice. Both in vitro and in vivo studies suggest
      improved killing with the sr39tk variant. Thus, the results suggest that the use
      of sr39tk in future trials of prostate cancer tk suicide gene therapy may be
      beneficial.

PMID- 11975846
TI  - Delivery of plasmid DNA to articular chondrocytes via novel collagen
      glycosaminoglycan matrices.
AB  - Our primary objective was to fabricate a porous gene-supplemented collagen
      glycosaminoglycan (GSCG) matrix for sustained delivery (over a period of several
      weeks) of plasmid DNA to articular chondrocytes when implanted into cartilage
      lesions. The specific aims of this in vitro study were to determine the release
      kinetics profiles of plasmid DNA from the GSCG matrices, and to determine the
      ability of the released plasmid DNA to transfect adult canine articular
      chondrocytes. In particular, we evaluated the effects of two variables, cross
      linking treatment and the pH at which the DNA was incorporated into the matrices,
      on the amount of the plasmid DNA that remained bound to the GSCG matrices after
      passive (nonenzymatic) leaching and on the expression of a reporter gene in
      articular chondrocytes grown in the GSCG matrices. Collagen-glycosaminoglycan
      matrices were synthesized without cross-linking, and by three cross-linking
      treatments: dehydrothermal (DHT) treatment, 1-ethyl-3-(3-dimethyl aminopropyl)
      carbodiimide (EDC) treatment, and exposure to ultraviolet (UV) radiation. The
      plasmid DNA was incorporated into the collagen-glycosaminoglycan matrices in
      solutions at pH 2.5 or 7.5. Transmission electron microscopy studies revealed
      plasmid DNA bound to the walls of the porous GSCG matrices. In general, the GSCG
      matrices fabricated at pH 2.5 retained a larger fraction of the initial DNA load
      after 28 days of incubation in Tris-EDTA buffer. The passive, solvent-mediated
      release of the plasmid DNA from the GSCG matrices showed a biphasic pattern
      consisting of a faster, early release rate over the initial 8 hr of leaching
      followed by a slower, late release rate that was relatively constant over the
      subsequent 28 days of leaching. Electrophoretic analyses revealed that the
      plasmid DNA released from the GSCG matrices fabricated at pH 2.5 had been
      linearized and/or degraded; whereas the plasmid DNA leached from the GSCG
      matrices prepared with a DNA solution at pH 7.5 was primarily supercoiled and
      linear. Plasmid DNA released from all GSCG matrix formulations was able to
      generate luciferase reporter gene expression in monolayer-cultured chondrocytes
      transfected with the aid of a commercial lipid reagent, and in chondrocytes
      cultured in the GSCG matrices without the aid of a supplemental transfection
      reagent. Luciferase expression in chondrocyte-seeded GSCG constructs was evident
      throughout the culture period (28 days), with the EDC and UV cross-linked
      matrices prepared at pH 7.5 providing the highest transgene expression levels. We
      conclude that released plasmid DNA continually transfected canine articular
      chondrocytes seeded into GSCG matrices in vitro for a 4-week period as evidenced
      by luciferase reporter gene expression. Thus, GSCG matrices can be fabricated to
      provide sustained release of plasmid DNA carrying a potential therapeutic gene.

PMID- 11975847
TI  - High-level transduction and gene expression in hematopoietic repopulating cells
      using a human immunodeficiency [correction of imunodeficiency] virus type 1-based
      lentiviral vector containing an internal spleen focus forming virus promoter.
AB  - Prolonged exposure of human hematopoietic stem cells (HSC) to growth factors for
      efficient transduction by murine oncoretroviral vectors has major detrimental
      effects on repopulating activity. In this study, we have used a vesicular
      stomatitis virus G envelope protein (VSV-G)-pseudotyped human immunodeficiency
      virus type 1 (HIV-1) lentiviral-based vector system to transduce cord blood (CB)
      CD34+ cells over a limited time period (< or =24 hours). Under these conditions,
      significant gene marking was observed in engrafted human lymphoid, myeloid, and
      progenitor cells in all transplanted Severe Combined Immunodeficient (SCID) mice.
      To enhance the level of gene expression in hematopoietic cells, we also generated
      a series of lentiviral vectors incorporating the spleen focus forming virus
      (SFFV) long terminal repeat (LTR) sequences, and the Woodchuck hepatitis virus
      posttranscriptional regulatory element (WPRE). By including the central
      polypurine tract (cPPT) sequence of HIV-1 we were then able to achieve high
      levels of transduction (over 80%) and gene expression in vivo after a single
      exposure to viral supernatant. These results demonstrate that lentiviral vectors
      are highly effective for gene transfer to human HSC, and that SFFV regulatory
      sequences can be successfully incorporated to enhance the long-term expression of
      a transgene in primary human hematopoietic cells in vivo.

PMID- 11975848
TI  - Use of spontaneous Epstein-Barr virus-lymphoblastoid cell lines genetically
      modified to express tumor antigen as cancer vaccines: mutated p21 ras oncogene in
      pancreatic carcinoma as a model.
AB  - Spontaneous Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (SP
      LCLs) can be easily obtained from latently EBV-infected cancer patients and used
      as a source of antigen-presenting cells (APCs) for immunotherapy. Using point
      mutated (codon 12) p21(ras) (muRas) as a model tumor antigen, we evaluated the
      practicability of using genetically modified SP-LCLs as cancer vaccines for
      patients with pancreatic cancer expressing mutated Ras (muRas). The repeated
      stimulation of peripheral blood mononuclear cells (PBMCs) from patients with
      muRas-LCLs elicited a strong, muRas-specific T cell response. A significant
      cytotoxic activity against EBV virus proteins or components of the expression
      vector was not observed. The T cells were able to recognize naturally presented
      muRas, as shown by their cytotoxicity against muRas (Gly-12 to Val-12 or Asp-12)
      expressing tumor cells. The T cell response was mainly MHC class I restricted,
      and peptides containing amino acids 5 to 14 of muRas-Val-12 and muRas-Asp-12 were
      identified as immunogenic peptides for HLA-A2. In contrast to the situation in
      patients with putatively muRas-primed T cells, muRas-LCLs were not able to prime
      naive T lymphocytes from healthy controls. Vaccination of a pancreatic cancer
      patient with muRas-LCL induced muRas-specific T cells in PBMCs after 4 weeks. We
      conclude that genetically modified muRas-LCLs can efficiently present tumor
      antigens to the immune system and induce antigen-specific cytotoxic T cell
      responses in vitro and in vivo.

PMID- 11975849
TI  - Effect of promoters and enhancers on expression, transgene DNA persistence, and
      hepatotoxicity after adenoviral gene transfer of human apolipoprotein A-I.
AB  - Liver-directed gene transfer offers new perspectives for the treatment of
      inherited metabolic diseases and disorders of lipoprotein metabolism. Potent
      expression cassettes for transgenes in the liver may optimize gene transfer
      efficiency and improve the therapeutic index of gene transfer vectors. An E(1)
      deleted adenovirus comprising the hepatocyte specific 256-base pair (bp) human
      apolipoprotein A-I (apo A-I) promoter, the genomic human apo A-I DNA, and four
      human apo E enhancers (AdA-I.gA-I.4xapoE) was associated with low hepatotoxicity,
      high transgene DNA persistence and absence of promoter shut-off, resulting in
      human apo A-I plasma levels above 100 mg/dl for 35 days in C57BL/6 mice. In the
      present investigation, the human apo A-I promoter was compared to the murine
      small nuclear RNA U1b, the human apolipoprotein C-II (apo C-II), and the human
      alpha(1) antitrypsin (hAAT) promoters and the effect of copy number and position
      of liver-specific human apo E enhancers in 16 adenoviral constructs was
      evaluated. The vector containing the 1.5-kb hAAT instead of the apo A-I promoter
      (AdhAAT.gA-I.4xapoE) induced 3.7-fold (p < 0.01) more human apo A-I reaching
      plasma levels above 300 mg/dl for 35 days. The composition of the expression
      cassette was a major determinant of human apo A-I transgene DNA copy number at
      day 35. Hepatotoxicity after adenoviral gene transfer was dependent on the
      promoter and the number of enhancers, and was higher with the enhancers in a 5'
      position. The combination of the hAAT promoter and four copies of the human apo E
      enhancer appears to be the expression cassette of choice for hepatocyte-specific
      overexpression of transgenes after gene transfer.

PMID- 11975850
TI  - Characterization of lentiviral vector-mediated gene transfer in adult mouse
      brain.
AB  - Lentiviral vectors are promising tools for gene transfer into the central nervous
      system. We have characterized in detail transduction with human immunodeficiency
      virus type 1 (HIV-1)-derived vectors encoding enhanced green fluorescent protein
      (eGFP) in the adult mouse brain. Different brain regions such as the striatum,
      hippocampus, and the lateral ventricle were targeted. The eGFP protein was
      transported anterogradely in the nigrostriatal pathway, but we have found no
      evidence of transport of the lentiviral vector particle. The performance levels
      of the different generations of packaging and transfer plasmid were compared.
      Omission of the accessory genes from the packaging plasmid resulted in a modest
      decrease in transgene expression. Inclusion of the woodchuck hepatitis
      posttranscriptional regulatory element, on the one hand, and the central
      polypurine tract and termination sequences, on the other hand, in the transfer
      vector each resulted in a 4- to 5-fold increase in transgene expression levels.
      Combination of both elements enhanced expression levels more than the sum of the
      individual components, suggesting a synergistic effect. In the serum of mice
      injected with lentiviral vectors a humoral response to vector proteins was
      detected, but this did not compromise transgene expression. Immune response to
      the transgene was found only in a minority of the animals.

PMID- 11975851
TI  - Adenovirally transduced dendritic cells induce bispecific cytotoxic T lymphocyte
      responses against adenovirus and cytomegalovirus pp65 or against adenovirus and
      Epstein-Barr virus EBNA3C protein: a novel approach for immunotherapy.
AB  - Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (Ad) cause
      significant morbidity and mortality in immunocompromised patients undergoing
      allogeneic stem cell transplantation. We have established a procedure to generate
      polyclonal cytotoxic T lymphocyte (CTL) populations with specificity against Ad
      and CMV or against Ad and EBV. Healthy donor-derived dendritic cells (DCs) were
      transduced with recombinant adenovirus encoding either CMV pp65 or EBV EBNA3C and
      used to stimulate autologous T cells. Stimulated T lymphocytes displayed specific
      simultaneous cytotoxicity against CMV and adenovirus and to a lesser extent
      against adenovirus and EBV. Recombinant vaccinia virus encoding individual
      adenovirus proteins showed that the T cell response to the adenovirus was
      directed mainly against the capsid protein hexon. The frequency of IFN-gamma
      secreting T cells was 0.02% for adenovirus alone, and 0.05 and 0.14% for
      adenoviruses encoding EBNA3C and pp65, respectively. pp65-specific CTLs killed
      autologous fibroblasts infected with the laboratory strain CMV AD169. The culture
      conditions were specific as alloreactive T cells were not expanded. Therefore,
      this approach could be considered in order to generate efficient virus cytolytic
      T cells to be used as adoptive immunotherapy in transplanted patients.

PMID- 11975852
TI  - Transduction of long-term-engrafting human hematopoietic stem cells by retroviral
      vectors.
AB  - Gene therapy using retroviral vectors to transfer functional exogenous genes into
      hematopoietic stem cells (HSCs) promises to provide a permanent cure for a wide
      array of both hematopoietic and nonhematopoietic disorders by virtue of the fact
      that retroviral vectors permanently integrate into the host cell genome and HSCs
      are able to self-renew and give rise to differentiated progeny throughout the
      life span of the patient. However, for transduction and genomic integration to
      occur, the target cells must undergo cell division and express the appropriate
      retroviral receptor, requirements that have thus far hindered attempts at
      inserting exogenous genes into human HSCs in vitro. In the present studies, we
      used the fetal sheep xenograft model of human hematopoiesis to evaluate whether
      human long-term engrafting HSCs could be transduced in vivo, within a fetal
      microenvironment. We transplanted adult human bone marrow-derived CD34(+)Lin(-)
      cells into preimmune fetal sheep recipients and subsequently (19 days later)
      administered clinical-grade murine retroviral vector supernatants to these fetal
      hematopoietic chimeras. Our results demonstrate that this approach successfully
      transduced adult human HSCs within all seven sheep that survived the procedure,
      and that these transduced HSCs had the ability to serially engraft primary,
      secondary, and tertiary fetal sheep recipients. Transgene expression persisted
      throughout the serial transplantation. The successful in vivo transduction of
      long-term engrafting human HSCs with the existing generation of murine retroviral
      vectors has significant implications for developing new approaches to pre- and
      postnatal gene therapy.

PMID- 11975853
TI  - High translation efficiency is mediated by the encephalomyocarditis virus
      internal ribosomal entry sites if the natural sequence surrounding the eleventh
      AUG is retained.
AB  - Internal ribosomal entry sites (IRES) allow cap-independent translation and are
      sequences that are often used in gene therapy for strategies in which several
      genes need to be expressed. In this study, two different sequences of
      encephalomyocarditis virus (EMCV) IRES were compared for their translation
      efficiency in the context of retroviral vectors. When the sequence surrounding
      the 11th AUG of the IRES was conserved (IRESg), the translation efficiency was
      significantly higher than if the AUG of the downstream gene started with the 11th
      AUG of the IRES (IRESb). The translation efficiency with IRESg was influenced by
      the cell type and also by the nature of the transgene.

PMID- 11975857
TI  - News from the Society for Women's Health Research. Survey findings indicate a
      need for further education on sex-specific medical facts.

PMID- 11975855
TI  - Evaluation of a unique oral contraceptive in the treatment of premenstrual
      dysphoric disorder.

PMID- 11975858
TI  - Observations from the CDC. An assessment of Pap smears and hysterectomies among
      women in the United States.

PMID- 11975859
TI  - Toward optimal health: the experts discuss hypertension [interview by Jodi
      Godfrey Meisler].

PMID- 11975860
TI  - Benefits and drawbacks of including consumer reviewers in the scientific merit
      review of breast cancer research.
AB  - BACKGROUND: This study assessed participant opinions about inclusion of breast
      cancer survivors as lay representatives in a scientific and technical merit
      review of proposals for the 1995 Department of Defense Breast Cancer Research
      Program (DOD BCRP). METHODS: The evaluation employed a prepanel and postpanel
      survey design, which was intended to elicit feedback about attitudes,
      perceptions, and beliefs toward collaborative consumer and scientist
      participation in scientific merit review. Qualitative methods were used to
      describe the consumers' and scientists' responses, to explore the significance of
      this interaction, and to gain an understanding of the benefits and disadvantages
      of bringing these participants together. RESULTS: Both groups were initially
      troubled about the consumers' lack of scientific background and questioned their
      qualifications and preparation for participation in a scientific panel. In
      particular, consumers were concerned that their judgments would not be taken
      seriously by scientists, a concern somewhat lessened by participation. After the
      meeting, scientists viewed the consumers as hard-working, dedicated survivors and
      advocates and endorsed the presence of carefully chosen lay panel members.
      Scientists were troubled that consumers potentially would have an impact on
      voting and on the subsequent scoring of proposals, a concern that was not
      validated by quantitative findings. CONCLUSIONS: As a result of these data, the
      DOD BCRP continues to embrace clarify the nature of collaborative participation
      in scientific merit review.

PMID- 11975861
TI  - Type A behavior and daily living activity among older minority women.
AB  - INTRODUCTION: The association between type A behavior pattern (TABP) and physical
      activity is unclear, with studies reporting both positive and negative results
      and some reporting no association. Because previous studies have looked primarily
      at the relationship between TABP and exercise, the purpose of this study was to
      assess the association between TABP and (1) total activity, (2) activity at work,
      (3) exercise, (4) household chores, (5) leisure activity, and (6) inactivity.
      METHODS: Two hundred twenty-seven women (111 African American, 116 Hispanic) from
      a larger study (Women on the Move) were used in the analysis for this study. The
      mean age was 49.3 years (SD 7 years), mean weight 77 kg (SD 17.6 kg), and mean
      body mass index (BMI) 30 (SD 6.5). As part of the Women on the Move Study,
      participants completed a 7-day diary and a 10-item Activity Temperament Scale.
      Multiple regression analysis was conducted to test the relationship between TABP
      and daily activity. Significant findings were observed for total activity and
      leisure activity with the Activity Temperament Scale summary score. Both had
      positive associations, indicating that those who had a higher score on the
      Activity Temperament Scale also had higher total activity kilocalories (kcal) and
      leisure activity kilocalories. Significant positive findings were also observed
      for total activity, leisure activity, and exercise with individual items on the
      Activity Temperament Scale. Household chores, work, and inactivity had
      significant negative associations with one or more of the individual items on the
      Activity Temperament Scale. CONCLUSIONS: Although previous studies have reported
      on TABP and physical activity (primarily exercise), these findings provide new
      information specific to daily living activity by dimension in an older minority
      population. Results suggest a positive association between TABP and daily living
      activity with a general pattern of higher scores associated with higher activity
      and lower scores associated with higher inactivity. However, even though some
      significant findings were observed, the overall models did not reveal meaningful
      associations.

PMID- 11975862
TI  - Gender differences in tobacco smoking: higher relative exposure to smoke than
      nicotine in women.
AB  - INTRODUCTION: Men and women are thought to regulate their smoking differently and
      to differ in their susceptibility to nicotine addiction. METHODS AND MATERIALS:
      Various measures of smoke exposure were compared between 400 current regular
      tobacco-dependent (DSM-IV) male and female light (1-15 cigarettes per day) and
      heavy (>15 cigarettes per day) smokers. Between 2 and 8 PM, blood was collected
      for nicotine and cotinine analysis, and breath carbon monoxide (CO) was measured.
      Individuals with genetic variants of the CYP2A6 gene were removed from analysis
      (n = 25). RESULTS: No significant difference was found in the number of
      cigarettes per day or CO levels between the sexes. However, females had
      significantly lower nicotine levels than males (16.9 +/- 0.6 vs. 21.1 +/- 0.07, p
      < 0.01). This is only partly explained by the fact that females smoked lower
      nicotine-containing cigarettes. Female heavy smokers demonstrated higher -log
      nicotine/CO values (a representation of cost of smoking) compared with male heavy
      smokers (0.1 +/- 0.02 vs. 0.02 +/- 0.01 mg/L ppm, p < 0.05). CONCLUSIONS: Thus,
      gender differences appear to exist in smoking behaviors, nicotine sensitivity,
      and nicotine requirements. These differences are expected to contribute to gender
      differences in health risks and cancers associated with smoking.

PMID- 11975863
TI  - Acute dehydroepiandrosterone (DHEA) effects on sexual arousal in postmenopausal
      women.
AB  - BACKGROUND: The age-related decline of dehydroepiandrosterone (DHEA) has prompted
      research on its experimental replacement in women. Although no relationship to
      sexual functioning in healthy women has been shown to date, DHEA replacement has
      potential for affecting sexual response. METHODS: To investigate DHEA effects, 16
      sexually functional postmenopausal women participated in a randomized, double
      blind, crossover protocol in which oral administration of DHEA (300 mg) or
      placebo occurred 60 minutes before the presentation of an erotic video segment.
      Blood DHEA sulfate (DHEAS) changes, subjective and physiological sexual
      responses, as well as affective responses were measured in response to videotaped
      neutral and erotic video segments. RESULTS: The concentration of DHEAS increased
      2-5-fold following DHEA administration in all 16 women. Subjective ratings across
      DHEA and placebo conditions showed significantly greater mental (p < 0.016) and
      physical (p < 0.036) sexual arousal to the erotic video with DHEA vs. placebo.
      Positive affect also increased during the erotic video across drug conditions.
      Vaginal pulse amplitude (VPA) and vaginal blood volume (VBV) demonstrated a
      significant increase (p < 0.001) between neutral and erotic film segments within
      both conditions (DHEA and placebo) but did not differentiate drug conditions.
      CONCLUSION: In sum, increases in mental and physical sexual arousal ratings
      significantly increased in response to an acute dose of DHEA in postmenopausal
      women.

PMID- 11975864
TI  - Physiological investigation of a unique extract of black cohosh (Cimicifugae
      racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic
      effect.
AB  - OBJECTIVE: This study sought to confirm the efficacy and safety of the currently
      recognized dose of Cimicifugae racemosae rhizoma (40 mg/day) and to evaluate a
      higher dose and its associated physiological effects. METHODS: We conducted a
      controlled, randomized, double-blinded parallel group study of perimenopausal and
      postmenopausal women treated with two different doses (39 mg and 127.3 mg) of a
      unique C. racemosa preparation over a 24-week period. Efficacy and tolerability
      were determined by the Kupperman Menopause Index, Self-Rating Depression Scale
      (SDS), a global assessment of tolerability, adverse events, routine hematology,
      and biochemical tests. To determine if the unique C. racemosa preparation exerts
      its effect through an estrogen-identical mode of action, we investigated vaginal
      cytology and gynecologically relevant hormones. RESULTS: Both perimenopausal and
      postmenopausal patients tolerated the treatment well, and menopausal symptoms
      decreased regardless of dose (responder rate 70% and 72%, respectively). The lack
      of change in vaginal cytology measures indicates a nonestrogenic effect of the
      tested extract in this critical organ. Likewise, the lack of significant changes
      in the levels of gynecologically relevant hormones does not indicate an overall
      estrogenic effect. CONCLUSIONS: The higher dose did not exert a significantly
      greater effect on any end point. Thus, the currently recognized standard dose of
      the isopropanolic aqueous C. racemosa extract should be preferred over the higher
      dose. Despite the absence of a placebo group, this study suggests that C.
      racemosa extract is associated with improvement in menopause symptoms without
      evidence of estrogenlike effects.

PMID- 11975865
TI  - Determinants of women's choice of obstetrician/gynecologist.
AB  - INTRODUCTION: There has been a reported increase in women's desires to have
      female medical providers. It is unclear if this finding extends to
      obstetrician/gynecologists or how important gender is relative to other factors
      in choosing a provider. This study seeks to address these issues. METHODS AND
      MATERIALS: In community locations in Brooklyn, New York, 537 women completed a
      questionnaire regarding demographics, gender of their current provider, and
      whether they considered age, gender, experience, location, or cost to be the most
      important factor in choosing an obstetrician/gynecologist. They rated their
      current experience and the importance of gender using a 10-point Likert scale.
      RESULTS: Overall, 61% of participants preferred a female provider. The proportion
      did not vary with gender of the interviewer or participants' age. A female
      provider was preferred by 56% of Protestants, 58% of Catholics, and 58% of Jews
      and by 74% of Hindus and 89% of Muslims (p = 0.02). Regardless of whether a woman
      preferred a male or a female provider, 38% of participants felt strongly (7-10 on
      Likert scale) that gender was important. There was no difference in satisfaction
      with current provider between women who preferred a male or female provider.
      Gender was as important in choosing an obstetrician as experience or cost. Almost
      as many women with a female provider indicated a preference for a male (46%) as
      women with a male provider who preferred a female provider (54%). CONCLUSIONS: A
      slight majority of these women, particularly those who are Hindu or Moslem or
      currently use a female, prefer female providers. Only a minority of these women
      feel strongly about their preference, and women with male providers are as
      satisfied as are women with female providers. Gender of provider was about as
      important as a physician's experience in choice of clinician.

PMID- 11975867
TI  - Women's health literaturewatch.

PMID- 11975866
TI  - Hysterectomy status and life satisfaction in older women.
AB  - OBJECTIVES: This cross-sectional, population-based study examines the long-term
      effect of hysterectomy on life satisfaction in 1177 women aged 55-94 years.
      METHODS: A 1992 mailed survey obtained information on menopausal history,
      including hysterectomy and oophorectomy status, and estrogen use. Two
      standardized measures ascertained general life satisfaction: the Life
      Satisfaction Index-Z (LSI-Z) and the Satisfaction with Life Scale (SWLS). A
      separate question asked participants to rate life satisfaction (better, the same,
      or worse) after menopause or hysterectomy compared with before. RESULTS: Twenty
      three percent of the women reported hysterectomy with bilateral oophorectomy an
      average of 24 years earlier, and 26% reported hysterectomy with ovarian
      conservation an average of 28 years earlier. Women who were 20 or more years
      posthysterectomy or postmenopause were significantly more likely to rate their
      life satisfaction as better than were women 5 or fewer years posthysterectomy or
      postmenopause (p < 0.01). Among women with a hysterectomy, 53% with oophorectomy
      and 60% with ovarian conservation rated life satisfaction better after
      hysterectomy. Only 42.2% of women without a hysterectomy rated life satisfaction
      as better after menopause (p < 0.001). Differences persisted after adjustment for
      age and other covariates: p < 0.01 for hysterectomy with ovarian conservation and
      p < 0.001 for hysterectomy with bilateral oophorectomy vs. no hysterectomy. Even
      among women who had never used estrogen, a significantly greater proportion of
      those who had a hysterectomy with ovarian conservation rated their life
      satisfaction as better compared with women who did not have a hysterectomy (p <
      0.05). There were no differences in standard life satisfaction scores (LSI-Z or
      SWLS) by hysterectomy status. CONCLUSIONS: There are no long-term adverse effects
      of hysterectomy on life satisfaction. When queried specifically, women report
      increased life satisfaction following hysterectomy. Relief from symptoms
      necessitating hysterectomy may be responsible for this increase. This difference
      may be specific to hysterectomy because there were no differences in general life
      satisfaction as assessed with standardized measures.

PMID- 11975868
TI  - [Domino or sequential liver transplantation. Is it a feasible technique?].
AB  - BACKGROUND: In domino liver transplantation (LT), the explanted liver of a
      patient with familial amyloidotic polyneuropathy (FAP) is donated to another
      patient. PATIENTS AND METHOD: Between February 1999 and March 2001 we performed
      131 LT with 121 cadaveric donors in our unit. Ten domino LTs were performed.
      RESULTS: Patients with FAP were younger (37 years) than recipients of the second
      LT (64 years). The evolution of patients undergoing transplantation for FAP was
      excellent and all are currently alive and without complications. Among recipients
      of the second LT, one patient died in the postoperative period. A further two
      patients died from tumoral recurrence and hepatitis C virus recurrence 18 months
      and 9 months after transplantation, respectively. The remaining patients have
      shown no symptoms of FAP during the follow-up. CONCLUSION: The results of this
      study show that domino LT is technically feasible. The technique increases the
      number of grafts without apparent risk either to the recipient with FAP or to the
      recipient of the latter's explanted liver.

PMID- 11975869
TI  - [Incidence and risk factors for hepatitis A in the province of Guadalajara
      (Spain)].
AB  - BACKGROUND: The decrease in the prevalence of hepatitis A in Spain may modify the
      characteristics of this infection because of the rise in the susceptible adult
      population. The aim of this study was to determine the incidence of this disease,
      as well as the epidemiological characteristics and the complications of patients
      diagnosed in the province of Guadalajara between 1991 and 1999. PATIENTS AND
      METHODS: The inclusion criterion was the presence of specific IgM together with
      an increase in alanine aminotransferase concentrations and/or symptoms compatible
      with acute hepatitis. RESULTS: The mean incidence was 7.13 cases/105 inhabitants.
      Considerable differences were found between years due to the presence of an
      outbreak. Most cases occurred in children and young adults. The most frequent
      risk factor found overall was contact with an infected individual but the
      distribution of risk factors differed between children and adults. CONCLUSIONS:
      The decrease in the prevalence of hepatitis A in Spain entails an increase in the
      susceptible adult population. Consequently, hepatitis A may cease to be a
      typically pediatric disease and may become one that also affects young adults in
      whom it may have different characteristics. This consideration should be borne in
      mind when designing a vaccination strategy.

PMID- 11975870
TI  - [The phospholipase A2 inhibitor, aristolochic acid, inhibits chloride secretion
      without altering barrier function].
AB  - AIM: To study the effect of aristolochic acid (AA) and the effect of
      phospholipase A2 (PLA2) on barrier function and electrogenic chloride secretion
      in intestinal epithelium. MATERIAL AND METHODS: Electrophysiological studies were
      performed in the T84 cell line and rat distal colon. Ionic secretion and
      transepithelial resistance were determined. RESULTS: Exogenous AA increased
      calcium-stimulated secretion in the T84 cell line. Incubation of rat distal colon
      in the presence of AA, a PLA2 inhibitor, reduced basal ionic secretion without
      affecting transepithelial resistance and inhibited ionic secretion stimulated by
      a cyclic adenosine monophosphate (AMPc) agonist, forskolin. In T84 cells, AA
      inhibited both carbachol- and forskolin-stimulated secretion. CONCLUSION: PLA2
      modulates electrogenic chloride secretion but has no effect on barrier function
      in the T84 cell line or in rat distal colon.

PMID- 11975871
TI  - [Amoxicillin-clavulanic acid induced hepatotoxicity with progression to
      cirrhosis].
AB  - Amoxicillin-clavulanic acid is a commonly used antibiotic in clinical practice.
      It is usually prescribed on an empirical basis and several cases of
      hepatotoxicity with cholestasis have been described. We report the case of a 42
      year-old man who developed an acute hepatocellular lesion with progression to
      cirrhosis. The patient received amoxicillin-clavulanic acid twice with an
      interval of four months. Other causes of hepatic failure were excluded. Although
      amoxicillin-clavulanic acid-induced hepatotoxicity has been widely documented,
      there are no other reports describing its progression to cirrhosis in an adult.

PMID- 11975872
TI  - [Development of inflammatory bowel disease in a husband and wife].
AB  - It is currently thought that chronic inflammatory bowel disease (IBD) may be due
      to the action of an as-yet unidentified external agent on genetically predisposed
      individuals. While genetic influence on the development of the disease has been
      widely studied, very little is known about the possible environmental agents that
      could influence its development. One example of the influence of environmental
      agents could be the development of chronic IBD in a husband and wife. We describe
      the case of a married couple; after more than 30 years of cohabitation, the wife
      developed fistulizing Crohn's disease and, 7 years later, the husband developed
      ulcerative proctosigmoiditis. Currently, approximately 70 cases have been
      described in the international literature but none have been reported in Spain.
      We discuss the characteristics of our patients compared with those described in
      published reports and stress the importance of describing these cases for the
      future identification of a possible external agent.

PMID- 11975873
TI  - [Toxic hepatitis associated with tamoxifen use. A case report and literature
      review].
AB  - Tamoxifen is an antiestrogenic drug that acts by binding to the estrogen
      receptor. The drug is used as a co-adjuvant treatment in advanced breast cancer
      expressing the oestrogen-receptor protein. Clinical trials of tamoxifen have
      shown its efficacy in reducing mortality and recurrence rates over a five-year
      treatment. Cases of tamoxifen-associated hepatotoxicity have been described,
      including cholestasis with or without cytolysis and steatohepatitis. We report
      the case of a female patient who developed hepatic alterations while undergoing
      continuous tamoxifen treatment. We also present an overview of similar cases
      published to date and comment on the advisability of continuing or suppressing
      this treatment in patients with hepatotoxicity or after a five-year treatment
      period.

PMID- 11975874
TI  - [Endoscopic capsule: present and future].

PMID- 11975875
TI  - [Barrett's esophagus: the biological reality of a premaligmant columnar
      metaplasia].

PMID- 11975876
TI  - [The polyposis register of St. Marks Hospital in London].

PMID- 11975877
TI  - [Hepatic insufficiency with portal hypertension as the only clinical
      manifestation of primary amyloidosis].

PMID- 11975878
TI  - [Crohn's disease and peritoneal cysts].

PMID- 11975879
TI  - [Spontaneous rupture of a pseudoaneurysm of the pancreaticoduodenal artery].

PMID- 11975880
TI  - [Tibolone-induced hepatotoxicity].

PMID- 11975881
TI  - [Inmunosuppression and liver transplantation in patients with hepatitis C virus
      infection].

PMID- 11975882
TI  - [Treatment of hepatitis C recurrence after liver transplantation. Influence of
      inmunosuppresive treatment of outcome].

PMID- 11975883
TI  - New strategies to optimize clinical outcomes with cyclosporine in liver
      transplantation.

PMID- 11975884
TI  - [Clinical and endoscopic prognostic factors in patients with bleeding peptic
      ulcer].
AB  - BACKGROUND: The main objectives of this study were to review the clinic and
      endoscopic variables of patients with upper gastrointestinal bleeding (UGB) due
      to peptic gastroduodenal lesions who were evaluated in our hospital during one
      year, to identify the characteristics associated with a negative evolution of the
      UGB and to analyse the characteristics of those patients who were discharged
      immediately after the endoscopy was performed. PATIENTS AND METHOD: A one-year
      retrospective analysis of all UGB episodes was performed. Patients having
      gastroduodenal ulcer or erosive gastritis/duodenitis at endoscopy were included.
      The prognostic value of several clinic, laboratory and endoscopic variables was
      evaluated. Persistence or recurrence of bleeding, surgery and mortality were
      considered as outcome variables (the variable evolution was categorized as
      negative when any of these was observed). RESULTS: 156 patients were identified,
      with a mean (SD) age of 61 (17) years. Melena was the most frequent UGB
      presentation (79%). 46% patients had associated diseases and 50% were taking
      gastroerosive drugs. Duodenal ulcer was the commonest cause of UGB (52%),
      followed by gastric ulcer (30%). The evolution of UGB was negative in 7% cases.
      Variables associated with a negative evolution in the multivariate analysis were:
      age, red hematemesis, systolic blood pressure >= 100 mmHg, heart rate >= 100
      b.p.m. and a more severe Forrest endoscopic classification. 11% patients were
      discharged immediately, without complications afterwards. If predictive variables
      obtained in the multivariate analysis would have been applied, hospitalization
      would have been avoided in 59 patients (38%) without subsequent complications.
      CONCLUSIONS: A number of clinic and endoscopic variables (UGB presentation form,
      blood pressure, heart rate, and Forrest endoscopic classification) with
      prognostic value have been identified in this study. These variables are easy to
      obtain and apply in clinical practice, allowing a precise estimate of the UGB
      evolution. Thus, a relatively high number of patients with UGB susceptible of
      ambulatory treatment and management can be reliably identified.

PMID- 11975885
TI  - [Heterozygous familial hypercholesterolemia in Spain. Description of 819 non
      related cases].
AB  - BACKGROUND: Heterozygous familial hypercholesterolemia (hFH) is an inherited
      disorder commonly found among the general population. Premature cardiovascular
      disease, especially coronary artery disease, is the most important complication
      in these patients. The aim of this study was to analyze the clinical
      manifestations and the characteristics of cardiovascular disease in the Spanish
      hFH population. PATIENTS AND METHOD: Analysis of 819 non-related cases (449
      females and 370 males), with a clinical diagnosis of familial
      hypercholesterolemia, from 69 lipid clinics. Clinical and lipid profile at
      diagnosis along with personal and familial backgrounds related to cardiovascular
      disease were registered in a central database. RESULTS: Mean total cholesterol at
      diagnosis was 412 (87) mg/dl in women, and 400 (78) mg/dl in men (p = 0.049). HDL
      c was higher in females than in males (57 [14] vs. 47.7 [12.7] mg/dl,
      respectively, p < 0.0001). Xantomas were present in 22.5% of cases, and 21.7% of
      subjects had evidence of premature cardiovascular disease which was more frequent
      in males than in females (30.8% and 14.3%, respectively; p < 0.001). In a
      multivariant analysis, a significant and positive correlation was observed
      between cardiovascular disease and age, gender, tobacco consumption, LDL-c
      levels, blood pressure and body mass index. CONCLUSIONS: The clinical
      manifestations and the presence of cardiovascular disease in Spanish hFH patients
      are similar to those described in other populations. LDL-c levels, age, gender,
      smoking, hypertension and body mass index are important predictors of
      cardiovascular disease in these patients.

PMID- 11975886
TI  - [Validation of the Spanish versions of the Montgomery-Asberg depression and
      Hamilton anxiety rating scales].
AB  - BACKGROUND: Affective and anxiety disorders (AfD & AnD) are the most common
      psychiatric diseases in the general population. This study's aim was to assess
      for the first time the psychometric properties of the Spanish translated versions
      of the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety
      Rating Scale (HARS), which are widely used both in medical care and clinical
      research. PATIENTS AND METHOD: A cohort, observational, prospective and
      multicentre study was conducted in clinically stable or unstable patients with
      AfD and AnD. The scales were administered at baseline and in a second study visit
      one week or 2 months later (to stable or unstable patients, respectively). The
      internal consistency, temporary stability, inter-raters reliability, factorial
      structure, convergent and discriminant validity, and sensitivity to change were
      all assessed for both scales. RESULTS: One hundred and eight AfD patients and 106
      AnD patients were recruited in 10 psychiatry care centres from a wide
      geographical distribution. Both scales showed adequate properties in terms of: a)
      discriminant validity (MADRS/HARS-Clinical Global Impression: p < 0.001); b)
      convergent validity (MADRS-Hamilton Depression Rating Scale: p < 0.05 and 0.01;
      MADRS/HARS-EuroQoL 5D: p < 0.05; HARS-State Trait Anxiety Inventory: p < 0.05);
      c) internal consistency (Cronbach's alpha: MADRS = 0.88; HARS = 0.89); d) test
      retest and inter-raters reliability (intraclass correlation coefficient: MADRS =
      0.94 and 0.98, respectively; HARS = 0.92 and 0.92), and, e) sensitivity to change
      (effect size: MADRS = 2.05; HARS = 1.36). CONCLUSIONS: Spanish versions of MADRS
      and HARS scales showed good psychometric properties, similar to those of the
      original scales. Therefore, these scales are suitable for use in clinical
      practice and research in Spain.

PMID- 11975887
TI  - [Analysis of the causes and potential avoidability of readmissions in an acute
      patients' hospital].
AB  - BACKGROUND: Rates of hospital readmissions are used as indicators of quality of
      health care. Yet specific causes of readmissions have not been sufficiently
      studied and an unified definition of such an indicator is lacking. Our goal was
      to determine the causes and potential avoidability of readmissions in our
      hospital and to identify a suitable definition of this indicator. PATIENTS AND
      METHOD:  DESIGN: Cross sectional study. SETTING: Hospital Costa del Sol
      (Marbella, Malaga). Subjects of study: Random sample of hospital discharges
      followed by a new admission within the next 6 months (n = 363). INTERVENTIONS:
      Determination of the causes and potential avoidability of readmissions, by means
      of a peer-review of medical records. Descriptive and logistic regression analysis
      of the variables contained in the Minimum Basic Data Set (MBDS) and related to
      the avoidability of readmissions. RESULTS: 19% (95% CI: 15.0-23.0) of hospital
      readmissions within 6 months after hospital discharge were attributed to
      potentially avoidable situations if the applied medical care had been modified
      during the previous episode. This figure reached 37% (95% CI: 27.4-47.3) for
      surgical services, 13% (95% CI: 8.7-17.6) for medical services and 12% (95% CI:
      2.9-20.6) for obstetrics. The MBDS variables related to the potential
      avoidability of readmissions were, for the whole hospital, 1) the shorter
      interval from the previous discharge and 2) the difference of diagnosis between
      both episodes. CONCLUSIONS: Most hospital readmissions are due to non-avoidable
      situations if the applied medical care had been modified during the previous
      episode. In order to detect potentially avoidable situations, definitions of
      readmission rates should only include early readmissions with a chief diagnosis
      other than that in the previous admission.

PMID- 11975888
TI  - [Dying for sport?].

PMID- 11975889
TI  - [Tropical diseases in the Western world].

PMID- 11975890
TI  - [Osteoporosis in the elderly: a worrying lack of medical treatment].

PMID- 11975891
TI  - [Emergency department short-stay unit as an alternative to standard inpatient
      care hospitalization].

PMID- 11975892
TI  - [Clinical and biologic issues of gastroenteritis due to nontyphoid Salmonella in
      elderly patients].

PMID- 11975893
TI  - [Severe sepsis and septic shock: crossroad between inflammation and coagulation].

PMID- 11975894
TI  - [Hemorrhagic complications after treatment with defibrotide in a case of severe
      veno-occlusive disease].

PMID- 11975895
TI  - [Long-term treatment of herpetic encephalitis with aciclovir. The role of PCR
      study in cerebrospinal fluid].

PMID- 11975897
TI  - [Applied cardiological research. Challenges for the new millenium].
AB  - Poor eating habits, a sedentary life style, and smoking have made acute coronary
      syndrome a disease characteristic of modern life. Although the widespread
      appearance of coronary heart disease has been delayed by 10 years, it is expected
      to be the primary cause of death in the world by the year 2020, in spite of the
      development of reperfusion therapy and the use of defibrillators. The incidence
      of coronary heart disease is spreading to more depressed areas and affecting an
      increasingly larger number of persons over 70, who are generally poorly
      represented in clinical studies and respond less favorably to treatment.
      Detaining the advance of this epidemic demands the development of a competitive
      research policy that includes rigorous training of researchers and scientific
      programs based on cooperation and teamwork. The success of this scientific
      strategy rests on public and private fund-raising to finance the anticipated
      priority areas of cardiovascular research in the coming years: vascular
      immunobiology, genome studies, tissue transplantation, and organogenesis.
      Advances in research complemented by the implementation of preventive measures
      based on a unified scientific approach and community educational campaigns could
      act effectively against the spread of cardiovascular disease in the world, thus
      avoiding otherwise inevitable social and economic consequences.

PMID- 11975898
TI  - [Sudden death and sport. Is there a feasible way to prevent it in athletes?].

PMID- 11975899
TI  - [Epidemiology of ischaemic heart disease in Spain: estimation of the number of
      cases and trends from 1997 to 2005].
AB  - INTRODUCTION AND OBJECTIVES: . The large amount of information on rates of acute
      coronary syndrome accumulated in Spain over the last two decades is summarized in
      this paper, which also estimates the number of cases expected in 2002 and the
      trend for 1997 to 2005. METHODS: Published information on the situation in the
      90's was reviewed and summarized. We present the incidence of acute myocardial
      infarction (AMI), and an estimate of the absolute number of patients expected for
      various acute coronary syndromes in each autonomous community in Spain in 2002,
      along with the trend for 1997 to 2005. RESULTS: Approximately 68,500 patients
      will suffer AMI in 2002 and 40,989 of them will be hospitalized, while the rest
      will die before admission. A further 24.9% of admitted patients will not survive
      28 days. Slightly less than half will be younger than 75 years old, an age with a
      better prognosis (28-day mortality 38.8%). Approximately 33,500 patients with
      unstable angina will be admitted, and 4.5% of them will die within 3 months of
      admission. Assuming the incidence of AMI remains stable, the absolute number of
      cases will increase by 2.28% yearly (9,847 cases in total) and hospitalizations
      for acute coronary syndromes will increase by 1.41% (8,817 cases in total)
      between 1997 and 2005. CONCLUSION: Ischaemic heart disease generates increasing
      demand for health care in Spain. Case fatality is high among the approximately
      68,500 AMI patients, given that scarcely two thirds will have been hospitalized
      in 2002.

PMID- 11975900
TI  - [Causes of sudden death during sports activities in Spain].
AB  - INTRODUCTION AND OBJECTIVES: Sudden death during sports activities has a profound
      impact on relatives, society, and athletes. Medical screening programs usually
      fail to prevent sudden death. We report the characteristics of a series of sudden
      deaths that occurred during sports in Spain. METHODS: We reviewed cases of sudden
      death that occurred during sports activities from 1995 to 2001 in the registries
      of the Institute of Toxicology of Madrid, Spain (Ministry of Justice). RESULTS:
      The series included 61 cases ranging in age from 11 to 65 years (average 31.9
      14.2), 59 males and 2 females. The sports most frequently involved were cycling
      (21), football (13), and gymnastics (5). The causes of death were atheromatous
      coronary disease: 25 (40.9%) (23 over 30 years); arrhythmogenic cardiomyopathy:
      10 (16.3%) (7 under 30 years); hypertrophic cardiomyopathy: 4 (6.5%); idiopathic
      left ventricular hypertrophy: 3 (4.9%); postmyocarditis myocardial fibrosis: 2
      (3.2%); dilated cardiomyopathy: 1 (1.6%); congenital anomalies in the origin of
      the coronary arteries: 2 (3.2%); aortic valve disease: 2 (3.2%); and others: 2
      (3.2%). In 10 cases (16.3%) (all under 30), the cause of death was undetermined.
      In 16 cases (26.2%) there was a known pathological antecedent. The disease
      responsible for death had been diagnosed in only three cases. CONCLUSIONS:
      Arrhythmogenic cardiomyopathy and severe left ventricular hypertrophy were the
      most common causes of sports-related death in persons under the age of 30. In 30%
      the cause of death was undetermined. Atheromatous coronary disease was prevalent
      over the age of 30 years and associated with cycling. Medical screening programs
      actually in use fail to detect a significant proportion of athletes at risk for
      sudden death.

PMID- 11975901
TI  - [Long-term prognosis of patients with myocardial bridge and angiographic milking
      of the left anterior descending coronary artery].
AB  - INTRODUCTION: Myocardial bridging with systolic compression (milking) of the left
      anterior descending coronary artery may be associated with myocardial ischemia.
      Little information is available about the long-term prognosis of patients with
      this coronary anomaly. MATERIAL AND METHODS: A review was made of coronary
      angiographies of patients diagnosed as ischemic heart disease made between 1994
      and 1999 in two centers. The long-term follow-up of patients with myocardial
      bridging and systolic compression of the left anterior descending coronary artery
      was analyzed. Data were collected by reviewing medical records and completed by
      telephone interview. RESULTS: Prevalence: 0.72%. Milking was observed in 60
      patients, but 25 of them were excluded due to associated hypertrophic
      cardiomyopathy, severe valvular disease, or coronary artery disease. The clinical
      follow-up was available for all patients (median: 43 months, range: 12-80
      months). Mean age 55.7 years (SD = 11.9). Men 74%. CLINICAL PRESENTATION: angina
      26 patients, atypical chest pain with positive non-invasive test 8, acute
      myocardial infarction 1. During follow-up, 1 patient died of sudden cardiac
      death. Seven patients continued to present stable angina CCS class I-II, coronary
      angiography was repeated in 5 patients, and one required percutaneous
      revascularization for symptoms. In 63% of cases, antianginal drugs were still
      needed at the end of follow-up period (beta-blockers or calcium antagonists).
      CONCLUSIONS: Patients with myocardial bridging and systolic compression of the
      left anterior descending artery have a good long-term prognosis, although more
      than half of them continue regular treatment with antianginal drugs. In a small
      percentage of cases percutaneous intervention must be performed and ischemic
      heart disease may appear in more aggressive forms (acute myocardial infarction or
      sudden death).

PMID- 11975902
TI  - [Influence of diabetes mellitus on clinical outcome after percutaneous coronary
      revascularization].
AB  - INTRODUCTION AND OBJECTIVES: Diabetes mellitus modifies the natural history of
      patients with coronary artery disease. The aim of this study was to assess the
      clinical outcome of diabetic patients with successful coronary angioplasty in our
      environment and to identify the factors predictive of complications during follow
      up. METHODS: A retrospective analysis was made of a series of 198 diabetics and
      who underwent angioplasty from September 1996 to January 2000 in our hospital. A
      group of 198 nondiabetic patients who subsequently underwent the same procedure
      was used as the control group. Death, non-fatal myocardial infarction, unstable
      angina resulting in hospitalization and coronary revascularization were
      considered adverse events during a 1 year follow-up period. RESULTS: The overall
      frequency of coronary adverse events in a 1-year follow-up was higher in
      diabetics (37%) than in non-diabetics (24%; p = 0.03). Diabetics had a less
      favorable clinical and angiographic profile and more frequent incomplete
      revascularization (43 vs 30%). Diabetics with incomplete revascularization were
      older (66.5 vs 53.2 years), had previous angioplasty more often, anatomically
      more unfavorable lesions (70 vs 51% type B2-C), and a smaller ejection fraction
      (54.7 vs 59.4%). Diabetics had more complications at 1 year of follow-up (37 vs
      24%; p = 0.03), mainly due to increased cardiovascular mortality in diabetics
      with incomplete revascularization (12 vs 2%). Multivariate analysis identified
      incomplete revascularization as the only correlate of clinical outcome. Diabetes
      per se was not predictive of complications during follow-up. CONCLUSIONS:
      Diabetics who undergo successful coronary revascularization have a less favorable
      clinical outcome than non-diabetic patients undergoing the same procedure at 1
      year of follow up. Incomplete revascularization is associated with a less
      favorable outcome.

PMID- 11975903
TI  - [Prognostic evaluation of patients with systolic dysfunction: functional and
      echocardiographic evaluation].
AB  - INTRODUCTION AND OBJECTIVES: Multiple clinical and echocardiographic parameters
      have been shown to have prognostic value in cases of left ventricular
      dysfunction. The purpose of this paper was to evaluate the relative predictive
      power of such parameters. METHODS: Ninety-one patients with systolic dysfunction
      were prospectively studied. Functional status was evaluated using the New York
      Heart Association classification and the 6-minute walking test. Other clinical
      and biochemical parameters were assessed, and an anatomic and functional
      echocardiographic study was performed. RESULTS: Mean follow-up was 16.5 months
      (SD: 6.95). Eighteen patients died and two underwent heart transplantation
      (cardiac death 22%). Multiple regression analysis showed that the only
      independent predictor of death was functional status. Functional classes I and II
      showed a 16-month mortality rate of 10%, class III 40% and class IV 83%. The
      mortality rate was 67% for patients who walked < 300 meters and 0% for those who
      reached > 500 meters. When echocardiographic results were analyzed separately,
      the only independent predictors of outcome were left atrial diameter and the E
      wave deceleration time. Deceleration times < 100 ms or atrial diameters > 5 cm
      were associated with a mortality rate of 46%. The correlation between E wave
      deceleration time and the walking test was r = 0.55, p < 0.0001. CONCLUSIONS:
      Functional status is the main predictor of outcome in patients with systolic
      dysfunction, whether assessed subjectively or estimated objectively by a walking
      test. Among echo-Doppler parameters, the deceleration time of the E wave and left
      atrial diameter gave similar prognostic information, although with less
      statistical significance. They can confirm or substitute the prognosis obtained
      by the functional classification.

PMID- 11975904
TI  - [Advantages of off-pump coronary bypass surgery in high-risk patients].
AB  - INTRODUCTION AND OBJECTIVES: Myocardial revascularization without cardiopulmonary
      bypass has been shown to reduce operative morbi-mortality. We report our recent
      experience with this novel technique in order to evaluate its theoretical
      advantages in comparison with conventional surgery. PATIENTS AND METHODS: This
      retrospective analysis included 547 consecutive patients undergoing isolated
      myocardial revascularization from December 1997 through November 2000. One
      hundred twenty-one off-pump patients were compared to 426 undergoing
      cardiopulmonary bypass. Logistic regression analysis was performed to find
      predictors of mortality, transfusion, postoperative atrial fibrillation and
      length of hospital stay. RESULTS: Off-pump patients were at greater risk: they
      were older, with a lower ejection fraction and a higher prevalence of unstable
      angina, heart failure and associated comorbidity. Off-pump surgery reduced
      transfusions (1 1 vs 1,9 2 blood units; p < 0.0001) and postoperative hospital
      stays (8.9 5 vs 11,3 7 days; p < 0.001). The off-pump group showed a trend toward
      reduced morbidity but the technique did not decrease hospital mortality.
      Cardiopulmonary bypass was an independent predictor of blood transfusion and
      longer hospital stay. Short-term follow-up revealed no significant differences in
      recurring angina or patency rates. CONCLUSIONS: Off-pump coronary bypass surgery
      is a good option in high-risk patients because it reduces the incidence of
      perioperative transfusion and the length of hospitalization. Furthermore, it
      showed a trend toward reduced morbidity. Mortality was not significantly higher
      in spite of the higher risk of the patients. Long-term longitudinal follow-up is
      mandatory to assess the true effectiveness of this technique.

PMID- 11975905
TI  - [Single-stage Fontan procedure: early and late outcome in 124 patients].
AB  - INTRODUCTION AND OBJECTIVES: The Fontan procedure was designed to palliate
      complex congenital heart disease with univentricular physiology. A retrospective
      study was made to document the determinants of early (</= 30 days) and late (>/=
      31 days) mortality with the modified Fontan procedure performed in one-stage over
      a 22-year period. MATERIAL AND METHODS: Between 1978 and 2000, 102
      atriopulmonary, 16 cavopulmonary, and 6 Kawashima type anastomoses were performed
      to palliate complex congenital heart defects in 124 patients with a mean age of
      7.3 4.7 years. Forty-five patient and procedure-related variables were analyzed
      in relation to mortality. All events were verified. RESULTS: There were 29 early
      (23%) and 20 late (16%) deaths. Estimated survival at 30 days, 2 years, 5 years,
      and 20 years was 78, 75, 66, and 50%, respectively. Subaortic stenosis, protein
      losing enteropathy, and arrythmia were observed in 8, 5 and 33 patients,
      respectively, after surgery. Univariate and multivariable analysis indicated that
      left ventricular end-diastolic pressure (>/= 13 mmHg), mean pulmonary pressure
      (>/= 19 mmHg), mitral stenosis/atresia, atrioventricular valve regurgitation,
      visceral heterotaxia, absence of fenestration, risk factors criteria, duration of
      extracorporeal circulation, and operative technique were associated with early
      mortality. Reoperation, arrhythmia, and pacemaker implantation were predictors of
      late death. Forty percent remained free from surgical or catheter reintervention
      after Fontan operation at 20 years. CONCLUSIONS: The outcome of Fontan procedure
      is profoundly affected by patient-related variables (ventricular function and
      pulmonary circulation). Postoperative arrhythmia and reoperation shortened the
      lifespan of the Fontan circulation model in patients with atriopulmonary
      connections. Total cavopulmonary anastomosis improves the physiology of
      univentricular circulation. In the light of our findings, the modified Fontan
      procedure (one or two stages) should be performed early in life to better
      preserve ventricular and pulmonary vascular function.

PMID- 11975906
TI  - [Genes and coronary heart disease].
AB  - The causes of atherosclerotic cardiovascular disease have been intensely
      scrutinized for the last few decades. Since the classic risk factors have been
      found to be incomplete predictors of the disease, additional risk factors based
      on molecular genetics are now being sought. Polymorphisms are gene variations
      that have only modest effects on the function of coded proteins or enzymes.
      However, they are common and may be risk factors in the presence of environmental
      risk factors (cholesterol, stress, tobacco). Recent advances in molecular biology
      have made it possible to detect numerous polymorphisms that might have a
      detrimental effect on vascular biology, suggesting the hypothesis that multiple
      polymorphisms in the presence of environmental factors could act synergistically
      in the pathogenesis of atherosclerosis and coronary heart disease, which are
      typically polygenic and multifactorial diseases. In this review, the current
      status of our knowledge of polymorphisms and mutations potentially implicated in
      the mechanisms of coronary artery disease is discussed. Genotype/phenotype, gene
      gene, and gene-environmental interactions related to lipid metabolism, the renin
      angiotensin-aldosterone and adrenergic systems, insulin resistance, oxidative
      stress and endothelial function, inflammation and thrombosis are analyzed.
      Individual coronary risk might be related to the presence of a critical
      accumulation detrimental polymorphisms.

PMID- 11975907
TI  - [Genetics and arrhythmias].
AB  - In the last 50 years we have been very successful at prolonging survival and
      improving the quality of life of patients with cardiac disease. The innovations
      in technology and pharmacology, better preventive and diagnostic tools have
      provided tremendous breakthroughs. However, despite our best efforts, the
      majority of cardiac diseases are structural in origin and will progress to their
      ultimate outcome. Curative therapies are not available due in part to our poor
      understanding of the basic mechanisms responsible for these diseases. The new
      developments in molecular genetics and biology are likely to change the way we
      approach a cardiac patient in the future. The diseases are presently being
      deciphered at the most basic level, and the information obtained opens new
      possibilities not only for better therapeutic and diagnostic measures but also
      for prevention of the disease.

PMID- 11975908
TI  - [Findings with a pressure guide wire in acute coronary syndrome].

PMID- 11975909
TI  - [Syncope of unknown origin in patients with permanent auriculoventricular block
      with an implanted pacemaker. Usefulness of the tilt table test].
AB  - Four female patients aged 26 to 71 years, with permanent complete AV heart block
      and an implanted pacemaker had syncope or presyncope after the pacemaker
      implantation. As part of the study protocol the tilt table test was done.
      Neurological disease, arrhythmias, pacemaker syndrome or dysfunction of the
      stimulation system were ruled out. A head up tilt was performed, isosorbide was
      used as pharmacological challenge, since the basal test was negative. In three
      patients this test was positive: in one patient possibly caused by postural
      orthostatic tachycardia syndrome, and two with neurally mediated syncope. In one
      patient it was not possible a diagnosis. The head-up tilt test is a useful
      procedure to identify the etiology of the appearance of syncope or presyncope
      after a pacemaker implantation in patients with complete and permanent AV block.

PMID- 11975910
TI  - [Pulsating thoracic mass as a main symptom of gigantic pseudoaneurysm of the
      ascending aorta].
AB  - The pseudoaneurysms of the ascending aorta are very infrequent but their
      diagnosis is important because of the associated high mortality. They usually
      appear in patients who have undergone aortic-related surgery, but the time that
      passes until they appear can be very prolonged and suspicious signs and symptoms
      can be quite anodyne. We present two cases of pseudoaneurysms of ascending aorta
      in two patients who underwent cardiovascular operations several months before,
      which were of such a considerable size that the first and practically the only
      symptoms were the sudden appearance of a pulsating thoracic mass because of
      pseudoaneurysm compression at this site.

PMID- 11975911
TI  - [Catheter-related central venous thrombosis in the course of an uncomplicated
      acute myocardial infarction: diagnostic usefulness of echocardiography].
AB  - In certain cases such as cancer patients or patients with coagulopathies, the
      venous thrombosis is a frequent complication that is associated with the
      implantation of central venous catheters. However, it is uncommon in other
      contexts, such as acute myocardial infarction without complications in its fifth
      day of evolution, after being treated with platelet inhibitors in addition to the
      initial anticoagulant and fibrinolytic therapy. We present a case of thrombosis
      in the superior vena cava and in the right atrium related to a peripherally
      inserted central catheter in this clinical context. The utility of
      transesophageal and transthoracic echocardiography in the differential diagnosis
      with other cardiac structures and in the evolutionary control is commented.
      Likewise, potential complications and the treatment of

PMID- 11975912
TI  - [Pulmonary thromboembolism after Fontan operation].
AB  - The fatal outcome in an eleven-year-old girl, one month after an extra-cardiac
      Fontan operation is reported. She was diagnosed with tricuspid atresia and had a
      Blalock Taussig shunt and a bidirectional Glenn procedure. The Fontan operation
      was performed using a Dacron conduit, fenestrated with a 6 mm Goretex tube. The
      first week after the operation she received low molecular weight heparin, then it
      was stopped and aspirin was started. One month after surgery she was admitted to
      the hospital because of sudden cyanosis, dyspnea, chest pain and syncope. A
      diagnosis of left pulmonary artery thrombosis without right to left shunt across
      the fenestrated tube was made. She was carried to the cardiac catheterization
      laboratory where a mechanical lysis of the thrombi was attempted. A local
      infusion of rtPA was started without improvement and she died 3 hours later.

PMID- 11975913
TI  - [Quitting smoking and social equity].

PMID- 11975914
TI  - [Clopidrogel in Acute Coronary Syndromes with Non-ST Elevation].

PMID- 11975918
TI  - History of the department of surgery in Cincinnati.
AB  - This narrative reviews the foundations and development of surgery in Cincinnati
      beginning with the surgical pioneers and the founding of the first medical
      institutions by Dr. Daniel Drake. The amalgamation of multiple medical schools
      resulted in university affiliation and a "full-time" chairman of surgery. The
      arrival of Dr. George Heuer and his Johns Hopkins group caused great turmoil but
      resulted in a strong department of surgery and residency program. Drs. Reid,
      Carter, and Altemeier succeeded Dr. Heuer and each contributed to the
      department's growth and success. Dr. Josef E. Fischer became chairman of surgery
      in 1978 and led the department through difficult times to its greatest expansion
      and development-bringing to a department with an outstanding history and
      tradition the reforms and modernizations needed to take it into the 21st century.
      Dr. Fischer has now returned to Boston and Harvard and was succeeded by Dr.
      Jeffrey Matthews in 2001. Under his capable leadership the department of surgery
      at the University of Cincinnati seems assured of a bright future.

PMID- 11975917
TI  - Festschrift for Josef E. Fischer, MD.

PMID- 11975919
TI  - Surgical organizations in the 21st century.

PMID- 11975920
TI  - Personal observations on the cultural evolution in academic surgery.
AB  - BACKGROUND: The changing environment in academic medical centers has had a major
      effect on the recruitment and the demographic characteristics of leadership
      positions in academic surgery. Categorization of "cultures" from the business
      model has been extrapolated into the academic surgical model. METHODS: The types
      of cultures in organizations according to Cameron and Quinnn at a school of
      management can be classified into four: clan culture, adhocracy culture,
      hierarchy, and market-driven culture. In addition, academic surgical chairmen
      were surveyed in 1981 and also 20 years later, 2001, by the author. This was done
      in an effort to determine whether there is a difference in the type of person
      being attracted to such positions and if there is demographic difference in
      academic chairmen over the two decades. RESULTS: The organizational profile of
      academic departments in 1980 is perceived to be more clan and adhocracy in type
      and less hierarchical and market driven. That has reversed itself dramatically
      two decades later with much of the energy of a department and structure based on
      hierarchy and the market. Also, in terms of the chairman, the mean age at the
      time of appointment in 1981 was 44 years and the mean age at time of appointment
      in 2001 was 49 years. In 1981 the years in grade was 9.4 years and in 201 it is
      7.1 years. The new chairman is now older and will not serve as long as his/her
      predecessor. CONCLUSIONS: There clearly has been a cultural evolution in academic
      surgery over the past two decades. The chairman has different priorities than
      chairmen 20 years ago. The success of an academic department will depend upon the
      adaptation to this cultural evolution and the understanding of the chairman as to
      what the job really is.

PMID- 11975921
TI  - Nutritional pharmacology in surgical patients.
AB  - The use of pharmaconutrition for supportive care of surgical patients is now well
      established, but the field is still in its infancy. Complex pharmaconutrient
      formulas containing arginine, glutamine, and n-3 fatty acids have been proven to
      shorten hospital stay, decrease the incidence of infection, and reduce hospital
      costs in selected groups of patients. The effects are greatest in those patients
      with severe trauma including burn injury, those undergoing major surgical
      procedures, especially when malnourished, and those who are critically ill ICU
      patients including patients with existing infection. The complex interaction of
      pharmaconutrients and other pharmacologic agents are just now beginning to be
      investigated.

PMID- 11975922
TI  - Quality of life in patients undergoing ileal pouch-anal anastomosis at the
      University of Cincinnati.
AB  - BACKGROUND: In 1978, Drs. Fischer and Martin were among the first to preserve
      anorectal continence and create a pelvic reservoir in adult patients, in what has
      become the ileal pouch-anal anastomosis (IPAA). METHODS: Here we review our
      institutions' experience with 379 of these procedures from 1978 to present. To
      assess the specific health concerns of patients with ulcerative colitis (UC) and
      familial adenomatous polyposis (FAP) and determine the effects of IPAA on health
      related quality of life, we evaluated patients with the SF-36, the Rating Form of
      Inflammatory Bowel Disease Patient Concerns (RFIPC), time trade-off questions,
      and a gamble question. RESULTS: IPAA patients did not differ from the general
      population in seven of eight general health categories assessed by the SF-36.
      When compared with the UC population as a whole using the RFIPC they had reduced
      concerns in almost all areas. In addition, time trade-off and gamble questions
      indicated that these patients, as a group, are willing to accept a significant
      risk of dying in order to achieve their results of the IPAA. CONCLUSIONS: This
      high level of satisfaction has led to the referral of patients who would not have
      otherwise considered a procedure requiring permanent ileostomy.

PMID- 11975923
TI  - Growth factor regulation of enterocyte nutrient transport during intestinal
      adaptation.
AB  - BACKGROUND: Intestinal adaptation occurs in response to injury or alteration in
      nutrient availability. It is both morphologic and physiologic in nature and can
      be mediated by growth factors and nutrients. Pathologic conditions such as short
      bowel syndrome and inflammatory bowel disease lead to derangements in nutrient
      absorption that may exceed the body's regenerative and adaptive capacity. Failure
      to fully adapt often results in long-term dependence on parenteral nutrition,
      leading to decreased quality of life and excessive medical expenses. The
      therapeutic use of appropriate growth factors may increase the adaptive
      capabilities of the gut. DATA SOURCE: Medline and current literature review.
      CONCLUSIONS: The major known nutrient transporters present in the gut and the
      mechanisms by which growth factors alter transport activity during intestinal
      adaptation are summarized. Growth factors have the potential to improve nutrient
      absorption in some bowel diseases.

PMID- 11975925
TI  - Cryoablation and liver resection for noncolorectal liver metastases.
AB  - BACKGROUND: Liver resection for noncolorectal liver metastases has merit for
      selected primary tumor types. The role of cryosurgical tumor ablation within this
      cohort of patients has not been evaluated. This is a single institutional review
      of treatment outcomes using cryosurgical ablation and conventional resection
      techniques for noncolorectal liver metastases. METHODS: The medical records of 42
      patients undergoing 48 hepatic tumor ablative procedures from February 1991
      through May 2001 at a single institution were retrospectively reviewed. Overall
      survival and local hepatic tumor recurrence-free survival were analyzed for
      different surgical procedures and primary tumor types. RESULTS: Overall survival
      rates at 1, 3, and 5 years are 82%, 55%, and 39%, respectively (median survival,
      45 months). Local hepatic tumor recurrence-free survival rates for resection only
      (n = 25) and cryosurgery with or without resection (n = 23), at 3 years are 24%
      and 19%, respectively. The survival rates at 5 years are 40% and 37%, for
      resection only and cryosurgery with or without resection, respectively.
      CONCLUSION: Cryosurgical hepatic tumor ablation for metastatic noncolorectal
      primary tumors results in survival and local hepatic tumor recurrence rates
      similar to resection alone. The combination of cryosurgery and resection extends
      the cohort of patients with surgically treatable disease.

PMID- 11975924
TI  - Mucosal and enterocyte IL-6 production during sepsis and endotoxemia--role of
      transcription factors and regulation by the stress response.
AB  - BACKGROUND: Sepsis and endotoxemia are associated with increased production of
      interleukin-6 (IL-6) in gut mucosa. Mucosal IL-6 may regulate enterocyte acute
      phase protein synthesis and intestinal IgA production. In addition, increased IL
      6 has been proposed to be a mechanism of loss of mucosal integrity in critical
      illness. The purpose of this review is to describe current knowledge of the
      regulation of IL-6 production in the enterocyte/mucosa during inflammation caused
      by sepsis and endotoxemia. DATA SOURCES: Recent publications describing the
      influence of sepsis, endotoxemia, and proinflammatory cytokines on
      mucosal/enterocyte IL-6 production. CONCLUSIONS: IL-6 production is increased in
      gut mucosa during sepsis and endotoxemia and in cultured enterocytes after
      treatment with endotoxin or proinflammatory cytokines. The IL-6 gene is regulated
      by multiple transcription factors, including NF-kappaB, AP-1, and C/EBP. Because
      of the multiple important biological roles of IL-6, understanding the cellular
      and molecular mechanisms of mucosal/enterocyte IL-6 production as well as methods
      to modulate IL-6 production is of clinical importance in the setting of sepsis
      and other critical illness.

PMID- 11975926
TI  - Current aspects of mucosal immunology and its influence by nutrition.
AB  - BACKGROUND: A significant body of clinical literature demonstrates that enteral
      feeding significantly reduces the incidence of pneumonia compared to patients fed
      parenterally. An immunologic link between the gastrointestinal tract and
      respiratory tract is postulated via the common mucosal immune hypothesis. This
      hypothesis states that cells are sensitized within the Peyer's patches of the
      small intestine and are subsequently distributed to submucosal locations in both
      intestinal and extra intestinal sites. This system is exquisitely sensitive to
      route and type of nutrition. DATA SOURCE: This review examines the laboratory
      data regarding cell numbers, cell phenotypes, cytokine profile, and immunologic
      function in both intestinal and extra intestinal sites in animals that have been
      administered either parenteral feeding or various types of enteral feeding. It
      also establishes links between a specific nutrient, glutamine, the enteric
      nervous system, by way of neuropeptides, and mucosal immunity. CONCLUSION:
      Progress in understanding relationships between nutrient availability, enteric
      nervous system stimulation, and nutrient delivery on mucosal immunity offers
      opportunities to explore immune systems previously not appreciated by clinicians
      and basic scientists. These opportunities offer new challenges to the physician
      scientist, basic scientist, and clinician to understand, manipulate, and apply
      these concepts to the critically ill patient population by favorably influencing
      immunologic barriers and the inflammatory response.

PMID- 11975927
TI  - Innovation in surgery: the rules of evidence.
AB  - The intellectual infrastructures of evidence-based medicine (EBM) are the levels
      of evidence and the grades of recommendation for the following types of research
      articles: therapy/prevention, etiology/harm, prognosis, diagnosis, differential
      diagnosis/symptom prevalence study, economic analysis/decision analysis. The
      levels of evidence for therapy (1 to 5) progress from systematic reviews (with
      homogeneity) of randomized control trials (RCT) of high quality, level 1, to
      level 5-expert opinion without explicit critical appraisal, or based on
      physiology, bench research, or "first principles." The grades of recommendation
      (A, B, C, D) are founded on the quality of the evidence defined by its level.
      These grades are aimed at helping clinicians understand the source from whence
      came statements in, for example, guidelines. The development of surgical
      procedures and their introduction into practice has not depended upon the RCT but
      rather upon an enthusiast performing a case series, sometimes with clearly
      defined results. Should all operations and procedures be evaluated by an RCT?
      Clearly not, and the levels of evidence support this quite clearly with the "all
      or none" research category as level 1c. This relates to frequent clinical
      situations requiring a solution often immediate, eg, pus, a ruptured aneurysm, a
      sucking chest wound, that do not lend themselves to a trial, as the control
      regimen (doing nothing) would lead to death. Techniques evolve with experience
      usually based on an understanding of pathophysiology. At what point should an RCT
      enter into the resolution of surgical therapies? Can observational studies
      correctly designed and carried out do the job? Two new study classifications have
      been introduced: in level 1, category c "all or none" studies; and in level 2,
      category c "outcomes" research. In neither is there much definition. Are these
      the areas into which the evaluation of new surgical procedures and technology
      should be placed? The surgical community is faced with dramatic changes in
      technology and evolving techniques, and needs to define the rules of evidence
      applicable to their discipline with the same rigor that the EBM gurus have used,
      in order for surgeons to define evidence-based surgical practice.

PMID- 11975928
TI  - Role of nitric oxide in wound repair.
AB  - After injury, wound healing is essential for recovery of the integrity of the
      body. It is a complex, sequential cascade of events. Nitric oxide (NO) is a small
      radical, formed from the amino acid L-arginine by three distinct isoforms of
      nitric oxide synthase. The inducible isoform (iNOS) is synthesized in the early
      phase of wound healing by inflammatory cells, mainly macrophages. However many
      cells participate in NO synthesis during the proliferative phase after wounding.
      NO released through iNOS regulates collagen formation, cell proliferation and
      wound contraction in distinct ways in animal models of wound healing. Although
      iNOS gene deletion delays, and arginine and NO administration improve healing,
      the exact mechanisms of action of NO on wound healing parameters are still
      unknown. The current review summarizes what is known about the role of NO in
      wound healing and points out path for further research.

PMID- 11975929
TI  - Direct inhibitory effect of erythromycin on human alimentary tract smooth muscle.
AB  - BACKGROUND: Erythromycin was found to stimulate motor activity in the upper
      gastrointestinal tract. However, in several smooth muscle preparations, it also
      elicited an inhibitory effect. Our aim was to study the effect of erythromycin in
      various human alimentary tract smooth muscles. METHODS: Using force measurements,
      we assessed the effect of erythromycin on electrically and chemically evoked
      contractions of isolated muscle strips of human gallbladder, small intestine, and
      colon. RESULTS: The muscarinic receptor agonist carbachol evoked contraction in
      gallbladder, ileum, and colonic smooth muscle that were reduced by erythromycin
      at 10(-4) M to 72% +/- 24%, 77% +/- 22%, and 76% +/- 22% of control values,
      respectively. Erythromycin did not affect contractions evoked by noncholinergic
      agents. Erythromycin's inhibitory effects were not altered by nerve blockade,
      indicating a direct muscle effect. Eryrthromycin also reduced contractions evoked
      by electrical stimulation at frequencies of 5, 10, and 20 Hz in the human
      gallbladder, ileum, and colon preparations. These contractions were reduced by
      erythromycin in a reversible and dose-dependent manner. CONCLUSIONS: Erythromycin
      antagonized direct cholinergic effects on various smooth muscles from the human
      alimentary tract in a concentration-dependent manner.

PMID- 11975930
TI  - Effect of laparoscopic antireflux surgery upon renal blood flow.
AB  - BACKGROUND: Hypercapnia and local pressure effects unique to CO(2) base minimally
      invasive surgery alter renal blood flow. We have demonstrated laparoscopic
      antireflux surgery to have an additional impact upon hemodynamics (decreased
      cardiac output), potentially extending known effects upon renal blood flow.
      METHODS: We measured renal blood flow with radioactive microspheres during
      laparoscopic antireflux surgery in a porcine model. Six pigs were anesthetized,
      monitoring lines were placed, and microspheres injected five time points
      associated with a laparoscopic antireflux operation. After euthanasia kidneys
      were retrieved and fixed, and representative samples counted for radioactivity
      specific for each of the five time points. RESULTS: The greatest reduction in
      renal blood flow was 36% below baseline (p<0.05). Concurrently, cardiac output
      had a maximum reduction of 39%. CONCLUSIONS: Laparoscopic Nissen fundoplication
      in this pig model is associated with a significant reduction in renal blood flow,
      probably related to reduction in cardiac output. Caution is warranted when
      considering laparoscopic antireflux surgery in patients with a compromised renal
      blood flow.

PMID- 11975931
TI  - Branched chain amino acids in heptatic encephalopathy.
AB  - BACKGROUND: Early theories or hepatic encephalopathy focused on ammonia-driven
      disruption of the Krebs cycle and cellular energy production. The "false
      neurotransmitter" theory directed attention toward the interactions of amino
      acids, metabolism, the blood-brain barrier and neurotransmission. As they
      evolved, these studies revealed surprising and subtle effects of ammonia on brain
      amino acid uptake. DATA SOURCES: Research over a 15-year period in Josef E.
      Fischer's laboratory explored many aspects of these interactions. Subsequent
      studies by others have confirmed and extended them into other areas. Insights
      from this work continue to stimulate attempts to confirm or disprove the clinical
      utility of branched chain amino acids. CONCLUSIONS: Increased understanding of
      the factors affecting ammonia, amino acid and neurotransmitter disturbances in
      chronic liver failure have made a significant and ongoing contribution to the
      study of metabolism in health and disease.

PMID- 11975932
TI  - Clinical potentials of neuropeptide Y family of hormones.
AB  - Neuropeptide Y (NPY) family of hormones exhibits a wide spectrum of central and
      peripheral activities mediated by six G-protein coupled receptor subtypes denoted
      as Y1, Y2, Y3, Y4, Y5, and y6. Investigations to date have implicated NPY in the
      pathophysiology of a number of diseases including feeding disorders, seizures,
      anxiety, diabetes, hypertension, congestive heart failure and intestinal
      disorders. These observations suggest that long-acting, potent NPY receptor
      selective agonists and antagonists developed could be used to treat a variety of
      diseases. These possibilities are discussed in this paper.

PMID- 11975933
TI  - Intestinal and hepatic response to combined partial hepatectomy and small bowel
      resection in mice.
AB  - BACKGROUND: Both partial-hepatectomy (PHx) and massive small bowel resection
      (SBR) are strong mitogenic signals to the remnant liver and intestine,
      respectively. This study tested the hypothesis that PHx was an additive signal
      for intestinal adaptation after massive SBR. METHODS: Male mice underwent either
      sham SBR or 50% proximal SBR. Mice from these two groups were then subjected to a
      70% PHx or sham PHx. After 3 days, parameters of intestinal adaptation and liver
      regeneration were recorded in the remnant intestine and liver, respectively.
      RESULTS: Intestinal adaptation following SBR occurred normally, but was not
      enhanced after concomitant PHx. On the other hand, SBR impaired the regenerative
      ability of the liver following PHx. CONCLUSIONS: Intestinal adaptation after SBR
      takes priority over liver regeneration after PHx. These data implicate a
      hierarchy with regard to adaptive alterations to organ loss and endorse an
      important role for the intestinal mucosa in the regulation of hepatic
      regeneration.

PMID- 11975934
TI  - Effect of hypergastrinemia on pancreatic carcinogenesis.
AB  - BACKGROUND: Previous studies in our laboratory demonstrated that pancreatic
      carcinomas in rodents express receptors for the peptide hormone gastrin that are
      not present in normal adult pancreas. In view of an abundant literature
      suggesting that gastrin may promote growth of various gastrointestinal tissues
      and tumors, the effect of hypergastrinemia on the process of pancreatic
      carcinogenesis was evaluated. METHODS: Rats received subcutaneous injections of
      the pancreatic carcinogen azaserine at 19 and 26 days of age. Starting at 12
      months of age, animals were randomized to treatment with the proton pump
      inhibitor lansoprazole or vehicle by gavage for 6 months. At autopsy, pancreatic
      wet weight normalized to body weight was recorded, as well as the number of
      benign and malignant pancreatic lesions. RESULTS: Serum gastrin levels were
      determined by radioimmunoassay and showed a greater than two-fold increase in
      lansoprazole-treated animals. Pancreatic wet weight in hypergastrinemic rats was
      increased compared to controls (p <0.05). Premalignant lesions such as
      acidophilic atypical acinar cell foci, adenomas, heterogeneous phenotypic
      populations of nodules within nodules, and carcinoma-in-situ were not increased
      in the hypergastrinemic group. Likewise, there was no difference in the incidence
      of invasive carcinoma in hypergastrinemic animals (10%) compared to controls
      (5.7%). CONCLUSION: Hypergastrinemia stimulated an increase in pancreatic weight,
      but did not stimulate development of premalignant lesions or progression to
      cancer in the azaserine model of rat pancreatic acinar cell carcinoma.

PMID- 11975935
TI  - Principles and practices for treatment of cutaneous wounds with cultured skin
      substitutes.
AB  - BACKGROUND: Skin substitutes prepared from cultured skin cells and biopolymers
      may reduce requirements for donor skin autograft, and have been shown to be
      effective in treatment of excised burns, burn scars, and congenital skin lesions.
      DATA SOURCES: Cultured skin substitutes (CSS) generate skin phenotypes (epidermal
      barrier, basement membrane) in the laboratory, and restore tissue function and
      systemic homeostasis. Healed skin is smooth, soft and strong, but develops
      irregular degrees of pigmentation. Quantitative analysis demonstrates that CSS
      closes 67 times the area of the donor skin, compared to less than 4 times for
      split-thickness skin autograft. CONCLUSIONS: CSS reduce requirements for donor
      skin autograft for closure of excised, full-thickness cutaneous wounds, and
      demonstrate qualitative outcome that is not different from meshed, split
      thickness autograft. These results offer reductions in morbidity and mortality
      for the treatment of burns and chronic wounds, and for cutaneous reconstruction.

PMID- 11975936
TI  - Immediate early genes and p21 regulation in liver of rats with acute hepatic
      failure.
AB  - It has been observed that liver regeneration in acute hepatic failure (AHF) is
      suppressed [Eguchi et al. Hepatology 1996;24(6):1452-9]. The molecular mechanism
      regulating this inhibition is not known. We previously reported that in AHF rats,
      hepatocyte proliferation was significantly impaired with elevation in serum IL-6,
      TGF-beta1, and HGF [Kamohara et al. Biochem Biophys Res Commun 2000;273(1):129
      35]. Following either 70% partial hepatectomy (PH) or liver injury, quiescent
      mature hepatocytes are "primed" to re-enter the cell cycle. The process of
      "priming" appears to be triggered by extracellular cytokines (IL-6 and TNF-alpha)
      and is characterized by expression of immediate early genes. Under the
      stimulation of growth factors such as HGF, "primed" hepatocytes exit the G1 phase
      of the cell cycle. G1-associated cyclins and their inhibitors play a pivotal role
      in G1/S cell cycle transition. Here, we demonstrate that immediate early gene
      (i.e. c-myc, c-fos) expression and AP-1 activity are preserved in AHF rat livers
      despite absence of hepatocyte proliferation. In contrast, p21 mRNA and protein
      are both over-expressed in AHF livers compared to livers from rats undergoing PH;
      this elevation leads to inhibition in Cdk2 activity, resulting in G1 cell cycle
      arrest and inhibition of regeneration.

PMID- 11975937
TI  - Anatomic and functional characteristics of the rat ileal pouch.
AB  - BACKGROUND: The definitive operation for chronic ulcerative colitis (UC) and
      familial adenomatous polyposis is total proctocolectomy with ileal pouch-anal
      anastomosis (IPAA). Mild inflammation (pouchitis) is omnipresent in pouches and
      becomes severe in 50% of UC patients with IPAA. The etiology of pouchitis is
      likely due to combined genetic, microbial, and immunologic factors. Epithelial
      cell exposure to surgical trauma and/or to changes in intestinal bacterial
      composition may account for the inflammatory infiltrate. Progress in
      understanding pouchitis is restricted by the lack of suitable animal models.
      METHODS: An ileal pouch-rectal anastomosis [IPRA] in rats was developed to
      reproduce a model of human IPAA and clinical, gross and histologic criteria were
      determined. RESULTS: Many shared features with human ileal pouch were observed.
      CONCLUSION: IPRA is an important in vivo model to study mechanisms of repair,
      defense and immunity that may contribute to pouchitis.

PMID- 11975938
TI  - Reversal of cancer-related wasting using oral supplementation with a combination
      of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine.
AB  - BACKGROUND: Cancer-related cachexia is caused by a diverse combination of
      accelerated protein breakdown and slowed protein synthesis. The hypothesis
      proposed in this study is that supplementation of specific nutrients known to
      positively support protein synthesis and reduce protein breakdown will reverse
      the cachexia process in advanced cancer patients. METHODS: Patients with solid
      tumors who had demonstrated a weight loss of at least 5% were considered for the
      study. Patients were randomly assigned in a double-blind fashion to either an
      isonitrogenous control mixture of nonessential amino acids or an experimental
      treatment containing beta-hydroxy-beta-methylbutyrate (3 g/d), L-arginine (14
      g/d), and L-glutamine (14 g/d [HMB/Arg/Gln]). The primary outcomes measured were
      the change in body mass and fat-free mass (FFM), which were assessed at 0, 4, 8,
      12, 16, 20, and 24 weeks. RESULTS: Thirty-two patients (14 control, 18
      HMB/Arg/Gln) were evaluated at the 4-week visit. The patients supplemented with
      HMB/Arg/Gln gained 0.95 +/- 0.66 kg of body mass in 4 weeks, whereas control
      subjects lost 0.26 +/- 0.78 kg during the same time period. This gain was the
      result of a significant increase in FFM in the HMB/Arg/Gln-supplemented group
      (1.12 +/- 0.68 kg), whereas the subjects supplemented with the control lost 1.34
      +/- 0.78 kg of FFM (P = 0.02). The response to 24-weeks of supplementation was
      evaluated by an intent-to-treat statistical analysis. The effect of HMB/Arg/Gln
      on FFM increase was maintained over the 24 weeks (1.60 +/- 0.98 kg; quadratic
      contrast over time, P <0.05). There was no negative effect of treatment on the
      incidence of adverse effects or quality of life measures. CONCLUSIONS: The
      mixture of HMB/Arg/Gln was effective in increasing FFM of advanced (stage IV)
      cancer. The exact reasons for this improvement will require further
      investigation, but could be attributed to the observed effects of HMB on slowing
      rates of protein breakdown, with improvements in protein synthesis observed with
      arginine and glutamine.

PMID- 11975940
TI  - Academic surgery at the University of Cincinnati: the legacy of Josef E. Fischer.

PMID- 11975939
TI  - Quantitative in vivo assessment of arginine utilization and nitric oxide
      production in endotoxemia.
AB  - BACKGROUND: Until recently no methods were available to quantitate nitric oxide
      (NO) production in vivo. The advent of stable isotope techniques has allowed
      quantitation of NO production in different animal models and human disease
      states. METHODS: In vivo NO production was assessed with the use of stable
      isotope labeled arginine. Enrichments of metabolites were measured by liquid
      chromatography-mass spectrometry (LC-MS). Knock-out mice were used to assess the
      influence of knocking out inducible NOS (iNOS) or constitutively expressed NOS
      (cNOS) on arginine-NO metabolism. Pig models were used to assess the role of
      individual organs on arginine-NO fluxes. RESULTS: In mice under basal conditions
      cNOS mediates half of the NO production. After endotoxin challenge NO production
      doubles as a result of iNOS induction and cNOS-mediated NO production is
      downregulated. In larger animal models (pig) whole body NO production is
      augmented after endotoxin challenge, largely resulting from NO production in
      liver, intestine and kidney. Arginine supplementation increases NO production in
      pigs in liver, intestine and kidney both in the basal state and after endotoxin
      challenge. CONCLUSIONS: Stable isotope techniques employing LC-MS allow in vivo
      assessment of NO production in small and large animal models and in patients.
      This allows definition of the role that iNOS and cNOS-mediated NO production play
      in several disease states.

PMID- 11975941
TI  - Hyperemesis gravidarum complicated by Wernicke's encephalopathy.
AB  - BACKGROUND: Wernicke's encephalopathy is usually associated with alcohol abuse,
      but can also occur with hyperemesis gravidarum. The effect of delay in thiamine
      replacement on fetal outcomes is unknown. We present a case of this complication.
      CASE: A primipara with hyperemesis was admitted for mental status changes in her
      14th week of pregnancy. Physical examination revealed a lethargic patient with
      ophthalmoplegia, ataxia, and hyporeflexia. Parenteral thiamine therapy was
      started. The patient improved rapidly although the ataxia persisted. A
      spontaneous abortion occurred 2 weeks later. CONCLUSION: Wernicke's
      encephalopathy can complicate hyperemesis gravidarum. Early thiamine replacement
      may decrease the chances of spontaneous abortion.

PMID- 11975942
TI  - Nonimmune "Fulminant" type 1 diabetes presenting with diabetic ketoacidosis
      during pregnancy.
AB  - BACKGROUND: Ketoacidosis in pregnant women with previously undiagnosed diabetes
      is rare. Although insulin-dependent diabetes has recently been classified as
      either autoimmune (type 1A) or nonimmune (type 1B; "chronic" and "fulminant"
      subtypes), the clinical characteristics of diabetes in such settings are not
      fully understood. CASE: We report two pregnant patients with previously
      undiagnosed diabetes. They presented with severe diabetic ketoacidosis
      characterized by an abrupt onset, normal, or slightly elevated level of
      glycosylated hemoglobin, absence of diabetes-related autoimmune antibodies, and
      features typical of the "fulminant" subtype of nonimmune diabetes. The fetuses
      died in utero, and the mothers became insulin dependent. CONCLUSION: The
      "fulminant" subtype of diabetes may be associated with fetal death.

PMID- 11975943
TI  - Episodic hypothermia with hyperhidrosis in a pregnant woman.
AB  - BACKGROUND: Episodic hypothermia with hyperhidrosis is a disorder of
      thermoregulation, believed to be secondary to a hypothalamic dysfunction, which
      affects the body's thermoregulatory centers. During this rare condition, the body
      may sweat profusely in an attempt to maintain a lowered body temperature set
      point. The exact cause of episodic hypothermia with hyperhidrosis is not known.
      CASE: A multigravida at 35 weeks' gestation presented with symptoms consistent
      with hypothermia, although she was diaphoretic. Her basal body temperature was
      91.2F, with a lowered blood pressure and heart rate. The fetal heart rate was 130
      beats per minute and reassuring. Assisted rewarming occurred over a period of 3
      hours, after which her temperature stabilized at 97.9F. The remainder of the
      pregnancy was uneventful, and the patient delivered a term infant with no
      apparent adverse effects from this episode. CONCLUSION: Episodic hypothermia with
      hyperhidrosis should be considered as a potential cause of hypothermia during
      pregnancy.

PMID- 11975944
TI  - Criterion for fetal primary spongiform cardiomyopathy: restrictive
      pathophysiology.
AB  - BACKGROUND: Most cardiomyopathies recognizable in utero are the dilated type-with
      dilated, poorly contractile left ventricle. We propose a diagnostic criterion for
      the rare spongiform (noncompacted) cardiomyopathy. CASES: Three perinatal cases
      with echocardiography and autopsy are presented. The apical ventricular
      myocardium was thickened and markedly trabeculated. The ventricles were not
      dilated in two, and the atria were enlarged in all. Hydrops and bradycardia were
      present in all three despite normal or only mildly diminished contractility.
      Although the cardiomyopathy was familial in two siblings, two of three cases were
      female, ruling out Barth syndrome (with sex-linked recessive inheritance).
      Although all three of our cases with hydrops died, rare survivors have been
      reported in the eighth decade. CONCLUSION: Although spongiform cardiomyopathy may
      eventually develop into a dilated cardiomyopathy, its early characteristic is
      relatively diagnostic: a restrictive cardiomyopathy with no enlargement of the
      ventricles and prominent atria.

PMID- 11975945
TI  - Tetany following resuscitation after abruptio placentae.
AB  - BACKGROUND: Serum ionized calcium and magnesium are normally decreased during
      later stages of pregnancy. A further rapid decline may be caused by the rapid
      infusion of blood bank products in which citrate is used as an
      anticoagulant/preservative. Tetany, as reported here, may be precipitated by such
      infusions. CASE: A gravid woman presented in hemorrhagic shock due to abruptio
      placentae. Rapid infusion of packed red blood cells and fresh frozen plasma
      precipitated signs of tetany, muscle rigidity, posturing, high airway pressure
      during mechanical ventilation, etc. Ionized calcium and magnesium blood levels
      were very low (0.58 mmol/L and 1.0 mg/dL, respectively), but responded to rapid
      electrolyte administration. CONCLUSION: Binding of calcium and magnesium by
      citrate may lead to hypo-ionized calcemic and hypomagnesemic tetany after rapid
      replacement of blood products in the pregnant patient. This consequence is
      worsened when extreme alkalemia due to respiratory or metabolic causes is also
      present.

PMID- 11975946
TI  - Type I von Willebrand's disease presenting as recurrent corpus hemorrhagicum.
AB  - BACKGROUND: Female patients with undiagnosed von Willebrand's disease may present
      with heavy menorrhagia. This is a case report of a patient with undiagnosed von
      Willebrand's disease presenting with recurrent corpus hemorrhagicum. CASE: A
      nulliparous woman presented with her second episode of hemoperitoneum secondary
      to a ruptured corpus hemorrhagicum. CONCLUSION: Patients with recurrent corpus
      hemorrhagicum may be at risk for von Willebrand's disease even if no history of
      menorrhagia or bleeding disorder exists.

PMID- 11975947
TI  - Granulosa cell tumor of the ovary: extensive late recurrence after initial occult
      microscopic disease.
AB  - BACKGROUND: Late recurrence can be extensive with initial, clinically
      undetectable, microscopic granulosa cell tumor of the ovary. CASE: We describe an
      83-year-old patient who presented with extensive recurrent granulosa cell tumor
      of the ovary 6 years after undergoing abdominal hysterectomy and bilateral
      salpingo-oophorectomy for atypical endometrial hyperplasia with an incidental
      microscopic finding of ovarian granulosa cell tumor. CONCLUSION: Patients must be
      monitored closely after a diagnosis of ovarian granulosa cell tumor, even if the
      tumor is occult.

PMID- 11975948
TI  - Molar cornual ectopic pregnancy.
AB  - BACKGROUND: Few cases of ectopic molar pregnancies have been reported. We present
      one such case of a molar cornual pregnancy. CASE: A woman at 12 weeks' gestation
      by last menstrual period presented with ultrasound evidence of a molar pregnancy
      and a surgical abdomen. Diagnostic laparoscopy revealed a large amount of free
      intraperitoneal blood. Laparotomy revealed villous-appearing tissue with numerous
      fluid-filled cysts erupting from the posterior aspect of the right uterine cornu.
      A cornual resection was performed, followed by a suction dilation and curettage
      (D&C). The pathologic findings from the cornual resection were consistent with a
      partial molar pregnancy, while the material from the suction D&C demonstrated no
      villi or trophoblastic tissue. CONCLUSION: A molar cornual ectopic pregnancy is
      presented.

PMID- 11975950
TI  - Pelvic vein thrombosis as a cause of acute pelvic pain.
AB  - BACKGROUND: Pelvic vein thrombosis may occur in nonpuerperal patients with
      hypercoagulable conditions and have significant sequelae. The purpose of this
      report is to describe a nonpuerperal woman with factor V Leiden mutation who
      developed acute pelvic pain secondary to pelvic varix thrombosis. CASE: A
      multiparous woman, status post-bilateral tubal interruption, presented with acute
      onset of severe left-sided pelvic pain 5-6 weeks from the onset of her last
      menstrual period. A pelvic computed tomography scan showed left pelvic varix
      thrombosis. Hematologic studies were consistent with heterozygous factor V Leiden
      mutation. The patient was treated with heparin and warfarin, and had complete
      resolution of her pain. CONCLUSION: Pelvic vein thrombosis may cause acute pelvic
      pain in nonpuerperal women, especially those with primary hypercoagulopathies.
      This should be included in the differential diagnosis of acute pelvic pain in
      reproductive-age women.

PMID- 11975949
TI  - Postmenopausal hyperthecosis: functional dysregulation of androgenesis in
      climacteric ovary.
AB  - BACKGROUND: Hyperandrogenism of ovarian origin is rare in postmenopausal women.
      However, there is evidence that the ovaries of postmenopausal women are active
      endocrine glands, secreting mainly androgens. CASE: A postmenopausal woman sought
      treatment for progressive hirsutism. Endocrine evaluation revealed androgen
      excess. Transvaginal ultrasound revealed enlarged ovaries. Hysterectomy and
      bilateral oophorectomy were recommended. However, surgery had to be withheld for
      6 months while the patient recovered from an acute myocardial infarction. In the
      interim, the patient's hyperandrogenemia was successfully treated with monthly
      injections of the gonadotropin-releasing hormone agonist (GnRH), leuprolide
      acetate. CONCLUSION: This report illustrates the potential for postmenopausal
      ovaries to become active androgen-secreting endocrine organs. It also
      demonstrates the efficacy of pharmacologic intervention for postmenopausal
      ovarian hyperthecosis when the patient is a poor surgical candidate.

PMID- 11975951
TI  - Fatal clostridial sepsis after spontaneous abortion.
AB  - BACKGROUND: Although obstetric mortality due to complications of Clostridium
      perfringens infection is rare at present, we report a case of fatal clostridial
      sepsis secondary to a septic spontaneous abortion. CASE: A woman at 6-8 weeks'
      gestation presented with vaginal bleeding and abdominal pain. Although afebrile,
      the patient was hypotensive, tachycardic, and tachypneic. Physical examination
      was remarkable for a 10-weeks'-gestation-size uterus, mild pelvic tenderness, a
      closed cervix without signs of trauma, and moderate vaginal bleeding. Laboratory
      studies were consistent with infection, hemolysis, and coagulopathy. Sonography
      demonstrated echolucencies consistent with gas formation in the endometrial
      cavity. Despite fluid resuscitation, transfusions, antibiotic therapy, and a
      dilation and curettage, persistent vaginal bleeding required an emergency
      hysterectomy. Hypotension ensued, and despite aggressive resuscitation attempts,
      the patient died. CONCLUSION: Rare cases of fatal sepsis secondary to pelvic
      infection with Clostridium perfringens continue to occur. Hemolysis, anuria,
      coagulopathy, and characteristic sonographic findings should heighten suspicion
      of this potentially fatal infection.

PMID- 11975952
TI  - Isolated multiple bilateral echogenic papillary muscles: A unique sonographic
      feature of trisomy 13.
AB  - BACKGROUND: Echogenic papillary muscles are noted in 30% of fetuses with trisomy
      13. All reported fetuses with trisomy 13 and echogenic papillary muscles have
      exhibited additional abnormal sonographic findings. CASE: A 21.7-week fetus
      demonstrated three papillary echogenicities in each cardiac ventricle during
      ultrasound examination. Chromosomal analysis of amniocytes showed the karyotype
      47,XX,+13. CONCLUSION: Multiple bilateral papillary muscles may provide the only
      sonographic sign of fetal trisomy 13.

PMID- 11975953
TI  - Rupture of the larynx in a newborn.
AB  - BACKGROUND: Lesions of the laryngotrachea due to repeated intubation trauma after
      birth are reported. CASE: A macrosomic neonate was born at term after uneventful
      pregnancy. On the basis of diminished uterine contractions and arrest of descent,
      the head was delivered by using obstetric forceps. No intubation was attempted
      after birth. Ten hours later, the infant developed acute life-threatening
      respiratory distress and subcutaneous emphysema. Intubation was impossible. Open
      surgical exploration of the neck revealed a rupture of the cricothyroid ligament
      within the larynx. The defect was closed immediately, and after artificial
      ventilation for 7 days, the infant was extubated. One year later, the child is
      developing satisfactorily, without stridor or hoarseness. CONCLUSION: In
      macrosomic neonates after traumatic delivery, a laryngotracheal lesion should be
      considered when respiratory distress syndrome combined with subcutaneous
      emphysema occurs.

PMID- 11975954
TI  - Primary psoas abscess complicating a normal vaginal delivery.
AB  - BACKGROUND: Psoas abscess is a rare and potentially dangerous complication of
      normal delivery. CASE: We describe a case of primary psoas abscess after normal
      vaginal delivery. A young woman presented with fever, left back pain, left lower
      abdominal pain, and hip pain starting on postpartum day 2. Computed tomography
      demonstrated a large retroperitoneal collection. Aspiration drainage of the
      abscess under computed tomography guidance isolated Streptococcus viridans, which
      responded to antibiotic therapy and percutaneous drainage with complete
      resolution. CONCLUSION: A high index of suspicion is necessary for diagnosis of
      psoas abscess, which should be considered in postpartum patients with pyrexia,
      back and hip pain, and a normal neurologic examination. Computed tomography is
      effective for diagnosis and allows percutaneous drainage of the abscess.

PMID- 11975955
TI  - Puerperal adrenal abscess complicating chorioamnionitis.
AB  - BACKGROUND: An abscess in the adrenal gland is a rare finding described only a
      few times in the literature. We present a case report of chorioamnionitis
      complicated by a puerperal adrenal abscess diagnosed and drained percutaneously
      using ultrasound and computed tomography. CASE: A 22-year-old woman delivered
      prematurely because of chorioamnionitis. Amoxicillin clavulanate was
      administered, and her fever defervesced. Six days later, the patient presented
      with a temperature of 40C and right flank pain. Workup revealed an abscess in the
      right adrenal gland, which was diagnosed by computed tomography scan, and then
      drained percutaneously. Follow-up revealed regression of the abscess to complete
      recovery. CONCLUSION: Adrenal abscess has not been described in the past as a
      possible complication of choriamnionitis. It is important to assess the entire
      abdominal cavity by ultrasound or computed tomography in febrile patients who do
      not respond to medical therapy.

PMID- 11975956
TI  - Atypical glandular cells of undetermined significance from extramammary Paget's
      of the bladder.
AB  - BACKGROUND: The clinical significance and appropriate diagnostic evaluation of
      atypical glandular cells of undetermined significance (AGCUS) on cervicovaginal
      Papanicolaou test have not been well established. CASE: A 53-year-old woman with
      AGCUS underwent colposcopy, cervical biopsy, hysteroscopy, dilation and
      fractional curettage, and subsequently hysterectomy with bilateral salpingo
      oophorectomy without abnormal findings. A repeat vaginal Papanicolaou test
      revealed malignant cells. Extramammary Paget's disease and urothelial carcinoma
      in situ were subsequently determined to be the source of the abnormal cells
      interpreted as AGCUS. CONCLUSION: AGCUS may be associated with extramammary
      Paget's disease and urothelial carcinoma. One should maintain a high index of
      suspicion for extragenital causes of persistent AGCUS.

PMID- 11975957
TI  - Positron emission tomography detection of breast cancer metastasis to the uterus.
AB  - BACKGROUND: We report the case of a patient presenting with moderate elevation of
      the tumor marker cancer antigen 15.3 during breast cancer follow-up. CASE: After
      a negative standard metastatic work-up, a positron emission tomography scan
      identified a localized central pelvic zone of uptake. Hysterectomy was performed,
      and pathology revealed a breast cancer metastasis within a previously known
      uterine leiomyoma. Positron emission tomography allowed assessment of soft
      tissues. CONCLUSION: With high sensitivity and specificity, positron emission
      tomography can be used to localize breast cancer metastases suspected by the
      presence of elevated serum tumor marker but not detected on standard metastatic
      workup.

PMID- 11975958
TI  - The role of inflammatory cytokines in Meigs' syndrome.
AB  - BACKGROUND: Inflammatory cytokines are known to induce capillary leakage and
      third-space fluid accumulation in numerous gynecologic and nongynecologic
      disorders. This study aimed to assess their role in Meigs' syndrome. CASE:
      Evaluation of serum, peritoneal, and pleural fluids retrieved from a patient
      suffering from Meigs' syndrome revealed high interleukin (IL)-1beta, IL-6, IL-8,
      and tumor necrosis factor (TNF)-alpha levels. After surgical removal of the
      ovarian tumor and with resolution of ascites and hydrothorax, serum levels of IL
      1beta, IL-6, and IL-8 declined, whereas tumor necrosis factor-alpha levels
      remained high. CONCLUSION: The correlation between these inflammatory cytokines
      and the clinical course of Meigs' syndrome suggests their involvement in the
      formation of ascites and hydrothorax in this disorder.

PMID- 11975960
TI  - Transurethral bladder eversion concurrent with uterovaginal prolapse.
AB  - BACKGROUND: Transurethral bladder eversion is rare. A case of transurethral
      bladder eversion with concurrent uterovaginal prolapse is presented. CASE: The
      patient was postmenopausal, had a long history of uterovaginal prolapse, and
      developed bladder eversion. Examination under anesthesia revealed full-thickness
      transurethral bladder eversion and complete uterine procidentia. Temporary
      reduction of the prolapse was done initially because of her unstable medical
      condition. After medical stabilization, definitive surgical reconstruction was
      completed by a vaginal approach. CONCLUSION: Full-thickness, transurethral
      bladder eversion can be surgically treated by a vaginal approach.

PMID- 11975959
TI  - Sebaceous gland hyperplasia of the vulva.
AB  - BACKGROUND: Sebaceous gland hyperplasia is a common condition of the face in
      elderly patients. We report a case of sebaceous gland hyperplasia on the vulva.
      CASE: A 19-year-old woman presented with a polypoid tumor on her left labium
      majus of which the greatest diameter was 2.5 cm, covered by normal appearing
      skin. Histologic examination revealed a sebaceous gland hyperplasia.
      Immunohistochemical techniques showed high expression of androgen receptors on
      sebaceous cells. CONCLUSION: Clinical and gross features of the two documented
      cases of sebaceous gland hyperplasia on the vulva are different from those of
      typical lesions on the face. Histologic study of a vulvar biopsy is required to
      reach a specific diagnosis of this hamartomatous benign condition.

PMID- 11975961
TI  - Dementia presenting as postpartum depression.
AB  - BACKGROUND: Other conditions that can mimic postpartum depression are rare but
      must be considered. CASE: A 37-year-old woman developed mood symptoms as well as
      progressive hyperphagia, hypersexuality, disinhibition, and impairment of
      judgment after delivery of her third child. She was unresponsive to multiple
      treatments for depression and was evaluated for frontal lobe syndromes.
      CONCLUSION: Frontotemporal dementia, formerly known as Pick disease, is a primary
      degenerative dementia for which no cause is clearly established. Family history
      or genetic abnormalities are found in about 50% of cases. The diagnosis is
      frequently missed or delayed, as in this case, because it occurs in a younger age
      group, presents with unusual signs and symptoms, and is far less prevalent than
      Alzheimer disease.

PMID- 11975962
TI  - Pregnancy with primary dilated cardiomyopathy.
AB  - BACKGROUND: Primary dilated cardiomyopathy is rare in women of childbearing age.
      The expected increase in intravascular volume and cardiac output during pregnancy
      is poorly tolerated by patients with primary dilated cardiomyopathy and may
      result in cardiac failure. CASE: A primigravid teenager with a history of primary
      dilated cardiomyopathy developed severe acute cardiac failure at 20 weeks'
      gestation. She required ventilation and was treated with inotropes and
      nitroglycerin. After counseling, she underwent termination of pregnancy using
      misoprostol. She recovered and was discharged 5 days after delivery. CONCLUSION:
      Pregnancy in patients with primary dilated cardiomyopathy can be extremely
      hazardous, resulting in cardiac failure and even death. A multidisciplinary
      approach and consideration of termination of pregnancy may be required in
      management of such patients.

PMID- 11975963
TI  - Cystic fibrosis and hemolytic uremic syndrome coexisting during pregnancy.
AB  - BACKGROUND: As more women with cystic fibrosis are living into their reproductive
      years, this disease can complicate pregnancy and coexist with other entities. We
      report a case of cystic fibrosis with hemolytic uremic syndrome. CASE: An 18-year
      old primigravida with cystic fibrosis was admitted at term with pulmonary
      symptoms, hypertension, and thrombocytopenia. She was delivered with the
      admitting diagnosis of severe preeclampsia. Postpartum, thrombocytopenia, and
      microangiopathic hemolytic anemia worsened. She developed renal failure and acute
      respiratory distress syndrome, requiring plasmapheresis, mechanical ventilation,
      and hemodialysis. Renal biopsy was consistent with the diagnosis of hemolytic
      uremic syndrome. CONCLUSION: Cystic fibrosis, a disease once managed
      predominantly by pediatric subspecialists, will be seen increasingly by
      physicians caring for adults, including obstetrician-gynecologists. We may also
      expect to see it coexisting with other disorders. The management of such patients
      may prove challenging.

PMID- 11975964
TI  - Ectopic pregnancy after cesarean hysterectomy.
AB  - BACKGROUND: Ectopic pregnancy after a total abdominal hysterectomy is rare and,
      for this reason, delay in diagnosis may occur when such a patient presents with
      abdominal pain. CASE: A multiparous patient with a history of cesarean
      hysterectomy 12 years before presented to the emergency department with abdominal
      pain and incidental positive urine beta-human chorionic gonadotrophin (hCG). A
      computed tomography scan revealed a loculated left cystic mass in the pelvis.
      Laparotomy findings revealed a left adnexal mass; pathology revealed chorionic
      villi consistent with pregnancy. CONCLUSION: Ectopic pregnancy may occur after
      hysterectomy, but typically presents near the time of surgery and is more
      commonly associated with vaginal hysterectomy. However, because ectopic pregnancy
      is possible after hysterectomy, it should be considered in the differential
      diagnosis of adnexal mass in such a patient.

PMID- 11975965
TI  - Factor VII deficiency in pregnancy treated with recombinant factor VIIa.
AB  - BACKGROUND: Factor VII deficiency is an autosomal recessive bleeding disorder
      with an incidence of one in 500,000. Few cases have been reported in pregnancy,
      and only two patients were treated with recombinant factor VIIa. In the past,
      fresh frozen plasma or factor VII concentrate has been the conventional treatment
      for this disorder. CASE: We report a case of factor VII deficiency diagnosed
      during pregnancy with a factor VII level of 1%. After prophylactic treatment with
      recombinant factor VIIa, the patient did not manifest any signs or symptoms of
      excessive bleeding during labor or postpartum. CONCLUSION: Given the inherent
      risks of transmission of human immunodeficiency virus and hepatitis with blood
      products, recombinant factor VIIa treatment is an alternative that is safe and
      effective during labor, delivery, and the puerperium.

PMID- 11975966
TI  - Celiac disease as a cause of chronic pelvic pain, dysmenorrhea, and deep
      dyspareunia.
AB  - BACKGROUND: Celiac disease may be subclinical and difficult to diagnose in
      adults. It has been associated with infertility and miscarriage but rarely with
      other gynecologic symptoms. CASE: A 43-year-old woman complaining of chronic
      abdominal and pelvic pain, deep dyspareunia, dysmenorrhea, diarrhea, and a 5-kg
      weight loss during the last 6 months was referred to our institution. Laboratory
      and clinical examinations were negative. At laparoscopy, numerous small
      leiomyomata were seen. A few filmy adhesions between the small bowel and the
      abdominal wall were lysed. With the exception of deep dyspareunia, all symptoms
      remitted after surgery, only to recur at 6 months of follow-up. A diagnostic work
      up for celiac disease revealed the presence of antigliadin and antiendomysial
      antibodies. The diagnosis was confirmed at gastroduodenoscopy including biopsy. A
      gluten-free diet was prescribed, and the patient is now free of symptoms.
      CONCLUSION: Celiac disease should be considered in women presenting with
      unexplained chronic pelvic pain, dysmenorrhea, and deep dyspareunia.

PMID- 11975967
TI  - A hair tourniquet resulting in strangulation and amputation of the clitoris.
AB  - BACKGROUND: Hair tourniquet syndrome involves fibers of hair or thread wrapped
      around an appendage producing tissue necrosis. Appendages commonly involved
      include the toe, finger, and penis. We report a hair tourniquet resulting in
      amputation of the clitoris. CASE: An adolescent presented with a 4-year history
      of intermittent genital pain that increased in severity over the preceding 5
      days. Physical examination revealed a necrotic clitoris surrounded by a black
      hair. During the examination, the tissue fell off resulting in immediate
      improvement in the patient's pain. CONCLUSION: We report a case of a clitoral
      hair tourniquet syndrome leading to autoamputation of the clitoris. A high index
      of suspicion for this condition is important because of the potential
      consequences of delayed treatment.

PMID- 11975968
TI  - Hysteroscopic management of cornual ectopic pregnancy.
AB  - BACKGROUND: Cornual ectopic pregnancies have traditionally been treated with
      systemic methotrexate, cornual resection, or hysterectomy. CASE: A 36-year-old
      newly gravida presented with an 8-week history of amenorrhea and a positive home
      pregnancy test. A transabdominal sonogram revealed a left cornual ectopic
      pregnancy. The patient was treated with multiple methotrexate doses, but the
      gestational sac persisted. Through the hysteroscope, the sac was ruptured, and
      the placental tissue was removed from the left cornu under sonographic guidance.
      Two weeks postoperatively, the patient's beta-human chorionic gonadotropin level
      was negative, and she had a normal pelvic examination and sonogram. CONCLUSION:
      Hysteroscopic removal under sonographic guidance after methotrexate treatment is
      a conservative option for the treatment of cornual ectopic pregnancy in some
      patients.

PMID- 11975969
TI  - Transitional cell ovarian carcinoma in a BRCA1 mutation carrier.
AB  - BACKGROUND: BRCA1 mutation carriers are at high risk of developing epithelial
      ovarian cancer, but the transitional cell variant has not been previously
      reported in these patients. CASE: A nulligravid, perimenopausal woman underwent
      exploratory laparotomy for a pelvic mass, ascites, and omental caking.
      Intraoperatively, frozen section of a tumor implant revealed high-grade
      epithelial ovarian carcinoma. Optimal surgical cytoreduction was performed. The
      final surgical pathology confirmed International Federation of Gynecology and
      Obstetrics stage IIIC transitional cell ovarian carcinoma. Her family history was
      significant for a sister with premenopausal breast cancer and a paternal aunt
      with ovarian cancer. The patient was counseled and elected to undergo genetic
      testing. Comprehensive gene sequence analysis detected the germline BRCA1
      5382insC mutation. CONCLUSION: Transitional cell ovarian carcinoma is a rare
      histologic variant of epithelial ovarian cancer that may occur in BRCA1 mutation
      carriers.

PMID- 11975970
TI  - Vaginal vault prolapse after nonsurgical and surgical treatment of MAAdullerian
      agenesis.
AB  - BACKGROUND: Women with Mayer-Rokitansky-Kuster-Hauser syndrome fail to develop
      mullerian ducts, present with primary amenorrhea, and an absent or rudimentary
      uterus and vagina. After creation of a neovagina, vaginal vault prolapse may
      occur because of lack of support to the artificially created vagina. CASES: The
      first patient presented with vaginal vault prolapse 10 years after her vagina was
      mechanically dilated. The second patient presented with vaginal vault prolapse 27
      years after a McIndoe procedure. CONCLUSION: Women with Mayer-Rokitansky-Kuster
      Hauser syndrome with an artificially created neovagina by dilatation or surgical
      procedure with a graft are at risk for vaginal vault prolapse. They can be
      successfully treated with abdominal sacrocolpopexy and paravaginal repair.

PMID- 11975971
TI  - Congenital malignant extrarenal rhabdoid tumor: prenatal ultrasound findings.
AB  - BACKGROUND: Congenital cancer is rare, and metastatic cancer of the infant at
      birth is even more unusual. Pregnancy management may be altered if fetal tumors
      are detected by prenatal ultrasound. CASE: We present a 29-week gestation with
      polyhydramnios and a fetus with a congenital malignant extrarenal rhabdoid tumor
      on the left neck and chest with generalized metastases. Cytogenetic analysis of
      the tumor cells revealed a trisomy 7. CONCLUSION: Prenatal ultrasound permits in
      utero detection of fetal tumors and identification of complications.

PMID- 11975972
TI  - Pregnancy and delivery in a patient with metastatic embryonal sarcoma of the
      liver.
AB  - BACKGROUND: Embryonal sarcoma of the liver is a rare undifferentiated mesenchymal
      neoplasm with a grave prognosis. CASE: We report a spontaneous uneventful
      pregnancy in a young woman with recurrent metastatic embryonal sarcoma of the
      liver after hepatectomy (twice) and radiochemotherapy. The patient chose to
      continue pregnancy despite her general condition and possible hazards to maternal
      and fetal well-being. She gave birth to a full-term healthy infant. Her disease
      recurred shortly after the delivery. CONCLUSION: According to a computerized
      search of the National Library of Medicine database, from 1966 to present, using
      the search terms "embryonal (or undifferentiated) sarcoma" and "liver" without
      language restrictions, this is the first reported case of pregnancy and delivery
      in a patient with embryonal sarcoma of the liver. It illustrates the clinical and
      ethical dilemmas associated with this complicated condition.

PMID- 11975973
TI  - Ureterocele causing anhydramnios successfully treated with percutaneous
      decompression.
AB  - BACKGROUND: Ureteroceles are congenital cystic dilatations of the submucosal
      segment of the distal ureter. We present a case of an intravesical ureterocele
      causing anhydramnios at 31 weeks' gestation. CASE: A primiparous woman near 20
      weeks' gestation had ultrasound evidence of a fetal duplicated right collecting
      system. At 31 weeks, an intravesical ureterocele was seen along with bilateral
      hydroureteronephrosis and anhydramnios. A single percutaneous needle
      decompression of the bladder and ureterocele successfully restored amniotic fluid
      volume. CONCLUSION: Follow-up ultrasounds are indicated when either a duplicated
      renal collecting system or a ureterocele is identified. In utero treatment is
      indicated only when amniotic fluid is compromised. Needle decompression should be
      first-line treatment, with more invasive methods reserved for failures of
      decompression.

PMID- 11975974
TI  - Abnormal first-trimester fetal nuchal translucency and Cornelia De Lange
      syndrome.
AB  - BACKGROUND: Cornelia de Lange syndrome is a genetic disorder associated with
      delayed growth and characteristic facial features. There is no definitive
      biochemical or chromosomal marker for the prenatal diagnosis of this syndrome. We
      describe a case of Cornelia de Lange syndrome associated with an increased nuchal
      translucency in the first trimester. CASE: A large nuchal translucency was
      identified in a fetus during a first trimester ultrasound. Subsequent second- and
      third-trimester sonograms demonstrated severe fetal growth restriction, limb
      shortening, and abnormal facial features, despite normal fetal karyotype per
      chorionic villus sampling. Neonatal evaluation confirmed the diagnosis of
      Cornelia de Lange syndrome. CONCLUSION: Sonographic finding of an increased
      nuchal translucency in early pregnancy is associated with fetal aneuploidy and
      various structural and genetic abnormalities. Increased nuchal translucency may
      identify fetuses that require vigilant assessment, especially when found in
      association with other abnormalities.

PMID- 11975975
TI  - Markedly elevated beta-hCG levels in a normal singleton gestation with
      hyperreactio luteinalis.
AB  - BACKGROUND: Human chorionic gonadotropin (hCG) is produced by the trophoblast
      early in pregnancy and peaks at a level of approximately 100,000 IU/liter around
      the ninth week of gestation. Abnormally high levels are usually noted in
      association with multiple gestation, molar gestation, and specific ovarian or
      gestational malignancies. CASES: A multiparous patient in the second trimester
      was referred for evaluation after a maternal triple marker screen was
      incalculable due to a beta-hCG level of 2.1 million IU/L. Targeted sonography
      revealed bilateral complex adnexal masses with a solid component of the left
      ovary, a normal fetus, and normal placenta. The patient underwent an exploratory
      laparotomy at 18 weeks' gestational age. A left oophorectomy was performed.
      Pathology confirmed hyperreactio luteinalis. The remainder of the pregnancy was
      remarkable for preterm labor and delivery at 35 weeks' gestational age. At
      delivery, the hCG level was noted to be 24,210 IU/L, and the fetus and placenta
      were normal. CONCLUSION: Markedly elevated hCG levels rarely occur in normal
      singleton pregnancy and can be associated with hyperreactio luteinalis. When
      noted, a work-up to evaluate possible malignancy, molar gestation, and multiple
      gestation should be pursued.

PMID- 11975976
TI  - Surgical treatment of primary hyperparathyroidism during the third trimester.
AB  - BACKGROUND: Primary hyperparathyroidism is a rare diagnosis in the third
      trimester of pregnancy. A 58% fetal complication rate, including perinatal death
      and preterm labor, following late gestation parathyroidectomy has been reported.
      These statistics, however, are based on small sample sizes and were reported when
      our current technology was unavailable. CASE: A 30-year-old woman presented in
      the early third trimester with primary hyperparathyroidism. Despite conservative
      management, her ionized calcium level increased to 1.88 mmol/L (normal 1.17-1.33
      mmol/L). At 3447 weeks, she had an uncomplicated parathyroidectomy. At 3837 weeks
      she delivered a 3182-g female infant. Neither the mother nor baby had
      complications. CONCLUSION: This supports the contention that pregnant women with
      hyperparathyroidism not controlled by conservative measures can be treated
      successfully with parathyroidectomy, regardless of gestational age.

PMID- 11975977
TI  - Clitoral cyst as a cause of ambiguous genitalia.
AB  - BACKGROUND: Ambiguous genitalia need appropriate evaluation, because a serious
      disease can manifest as this condition. CASE: A 28-year-old woman was referred
      with a "penis" present from age 12 years that enlarged throughout puberty but
      recently was unchanged. Differential diagnosis included true hermaphroditism;
      adrenal hyperplasia; clitoral, ovarian, and adrenal neoplasms; stromal
      hyperthecosis; polycystic ovarian syndrome; and exogenous androgen exposure. Free
      testosterone was not elevated. Dehydroepiandrosterone sulfate, 17
      hydroxyprogesterone, total testosterone, androstenedione, deoxycorticosterone, 11
      deoxycortisol, chromosomal analysis (46,XX), an intravenous pyelogram, and pelvic
      ultrasound were normal. The patient elected surgical removal. The mass was a
      chronic inflamed epidermoid cyst. CONCLUSION: If this patient had been
      appropriately evaluated earlier, she would have been spared anxiety and
      embarrassment over a simple epidermoid cyst.

PMID- 11975978
TI  - HLAMatchmaker: a molecularly based algorithm for histocompatibility
      determination. I. Description of the algorithm.
AB  - This report describes an algorithm for identifying acceptable HLA antigens for
      highly alloimmunized patients without the need for extensive serum screening.
      This algorithm is based on the concept that immunogenic epitopes are represented
      by amino acid triplets on exposed parts of protein sequences of human leukocyte
      antigen chains (HLA-A, HLA-B, and HLA-C) accessible to alloantibodies. A computer
      program (HLAMatchmaker) has been developed to determine class I HLA compatibility
      at the molecular level. It makes intralocus and interlocus comparisons of
      polymorphic triplets in sequence positions to determine the spectrum of non
      shared triplets on donor HLA antigens. In most cases is it possible to identify
      certain mismatched HLA antigens that share all their polymorphic triplets with
      the patient's HLA antigens and could therefore, be considered fully compatible.
      HLAMatchmaker permits also the identification of additional mismatches that are
      acceptable as determined from the triplet information on HLA-typed panel cells
      that do not react with patient's serum.HLAMatchmaker provides an assessment of
      donor-recipient HLA compatibility at the structural level and this algorithm is
      different from conventional methods based on the mere counting of numbers of
      mismatched HLA antigens or CREGs. This donor selection strategy is suitable
      especially for allosensitized patients in need of a compatible transplant or
      platelet transfusion.

PMID- 11975979
TI  - HLAMatchmaker: a molecularly based algorithm for histocompatibility
      determination. II. Verification of the algorithm and determination of the
      relative immunogenicity of amino acid triplet-defined epitopes.
AB  - HLAMatchmaker is a computer algorithm that assesses human leukocyte antigen (HLA)
      compatibility at the structural level by intralocus and interlocus comparisons of
      polymorphic amino acid triplets in antibody-accessible sequences of HLA class I
      molecules. This program permits the identification of mismatched HLA antigens
      that share all of their polymorphic triplets with the patient's HLA antigens and,
      therefore, could be considered fully compatible. The validity of this algorithm
      has been verified by analyzing the antibody specificity patterns of 127 well
      characterized sera (panel reactive antibody [PRA] > 80%) that had been screened
      by direct complement-dependent and/or anti-human globulin augmented
      lymphocytotoxicity testing with large HLA-typed cell panels. A 2 x 2 table-based
      Chi-square analysis program was applied to determine positive and negative
      correlations between serum reactivity and the presence HLA triplets assigned from
      the HLA types in the cell panel. The results indicate that high PRA patients do
      not produce antibodies to shared triplets on mismatched HLA antigens. Moreover,
      this serum analysis has permitted the identification of triplets with different
      degrees of immunogenicity as indicated by the frequencies of positive and
      negative correlations of serum reactivity with the HLA-typed cell panel.
      Mismatching for triplets with low immunogenicity provides further opportunities
      for identifying donors with acceptable HLA mismatches for highly sensitized
      patients.

PMID- 11975980
TI  - The number of amino acid residues mismatches correlates with flow cytometry
      crossmatching results in high PRA renal patients.
AB  - Highly sensitized renal transplant candidates present a group at high risk for
      acute and chronic rejection. The probability of finding compatible donors for
      these recipients is significantly lower in comparison to those who have low PRA
      values. As a consequence, these patients spend longer time on the waiting list
      and become tethered to dialysis. The results of final cross match (XM) are
      critical for making a decision about whether such a candidate receives an organ
      or not. The degree of donor and recipient HLA compatibility predicts the results
      of XM. The goal of this study was to expand a variety of acceptable HLA-AB
      mismatches (MM) for high PRA kidney recipients using the HLAMATCHMAKER algorithm.
      This strategy focuses on the fine structural features of HLA polymorphism
      comprising amino acid residues or triplets (AAT), which are located in alpha
      helical coils of HLA molecules and are available to antibodies. We analyzed serum
      samples from thirty-nine highly alloimmunized recipients (PRA > or = 85%). The
      level of sensitization was detected using FlowPRA Class I Screening Test. This
      group of transplant candidates included thirteen recipients who demonstrated
      negative results of final T/B FCXM and twenty-six, who were FCXM positive. The
      application of the HLAMATCHMAKER algorithm based on the HLA class I donor and
      recipient typing allowed us to detect the total number of AATMM as well as the
      number of immunogenic AAT in both FCXM negative and FCXM positive groups of
      recipients. Significantly greater numbers of both total and highly immunogenic
      AATMM have been emerged in the group of FCXM positive patients. Furthermore, the
      results of this analysis have shown a high degree of probability of positive FCXM
      if the number of highly immunogenic AATMM was > or = 1 (chi(2) = 22.9 Yate's
      correction; p = 0.000001). We did not observe overlapping between antibody
      specificity and permissible HLA-AB MM detected using the HLAMATCHMAKER strategy.
      Thus, the number of highly immunogenic AATMM can serve as a reliable predictive
      value for final FCXM results in highly sensitized renal transplant candidates.
      The HLAMATCHMAKER algorithm appears to be the proper strategy to find donors for
      high PRA recipients.

PMID- 11975981
TI  - HLA class II signals sensitize B lymphocytes to apoptosis via Fas/CD95 by
      increasing FADD recruitment to activated Fas and activation of caspases.
AB  - Human leukocyte antigen (HLA) class II heterodimers have a well defined role in
      peptide presentation to helper T lymphocytes. Moreover, engagement of HLA class
      II molecules leads to signal transduction in the antigen presenting cell.
      Signaling via HLA-DR increases CD95 mediated hypoploidy in B-cell blasts. Given
      the importance of CD95 for the homeostasis of lymphocyte populations, we examined
      the impact of the HLA-DR signal on the most proximal events in the CD95 apoptotic
      pathway. CD95 activation recruits the adapter molecule Fas-associated death
      domain protein (FADD) and thereby provides a scaffold for procaspase-8
      activation. The HLA-DR signal increased both recruitment of FADD and activation
      of caspases-3 and -8 via CD95 activation. Sensitization was tightly controlled
      because neither FADD recruitment to CD95 nor caspase activation was induced via
      HLA-DR alone. In contrast, the HLA-DR signal and the CD95 signal both led to
      decreased mitochondrial membrane potential. Taken together, these data indicate
      that ligand interaction with HLA class II molecules preactivates the antigen
      presenting cell for death in the event of a subsequent interaction with the CD95
      ligand. This would ensure termination of a specific immune response, particularly
      in cells with limited sensitivity to CD95 mediated apoptosis alone.

PMID- 11975982
TI  - Differential glycosylation of MHC class II molecules on gastric epithelial cells:
      implications in local immune responses.
AB  - Class II major histocompatibility complex (MHC) expression is a hallmark of
      antigen presenting cells (APC). Human gastric epithelial cells (GEC) express
      class II MHC and this expression increases during infection with Helicobacter
      pylori as does the number of CD4 T cells found adjacent or in between epithelial
      cells. These observations suggested that human GEC act as APCs. To characterize
      and compare class II MHC complexes with those present in conventional APC,
      immunoprecipitated class II MHC from GEC and B cells, as prototypic APC, were
      separated by two-dimensional electrophoresis. Although the composition of class
      II MHC from both cell phenotypes was similar, their electrophoretic mobility
      differed. Methodical elimination of carbohydrates, either enzymatically with
      endoglycosidase-H or blocking with tunicamycin, revealed that the deviations were
      due to differences in glycosylation in both cell phenotypes. When deglycosylated
      class II MHC alpha chains, beta chains, and the invariant chain from both cell
      phenotypes were mixed and run in the same gel, the core proteins had identical
      migration patterns. Because differences in glycosylation of class II MHC proteins
      may affect peptide selection and/or recognition by T cells, the noted differences
      in glycosylation of class II MHC expressed by GEC could be important in
      considering their potential role as APC locally.

PMID- 11975984
TI  - Linkage disequilibrium and age estimates of a deletion polymorphism (1597DeltaC)
      in HLA-G suggest non-neutral evolution.
AB  - A single base deletion in HLA-G (1597DeltaC) that is a null allele for the full
      length protein is found at frequencies of 6%-11% in populations of African
      descent. To test the null hypothesis that 1597DeltaC "drifted" to this frequency
      by neutral evolutionary processes, we compared the pattern of variation and
      linkage disequilibrium (LD) around this allele and around a conservative amino
      acid replacement polymorphism in HLA-G (T31S) in African-Americans and Nigerians.
      There was no significant LD between the 31S allele and flanking STRPs at 150-200
      kb in either sample, but significant LD was observed between the 1597DeltaC
      allele and the same flanking STRPs (p < 0.001 in both samples). To further
      characterize the evolutionary history of these variants, age estimates were
      determined assuming evolutionary neutrality. If these alleles were neutral, their
      frequencies indicate that they arose approximately 9500 (95% CI = 1557, 17557)
      generations ago (200,000 years). However, using LD to estimate the allele age,
      the 1597DeltaC allele was estimated to have arisen only 744 (95% CI = 375,2713)
      generations ago (18,000 years ago), whereas the 31S allele has a much older
      estimate of 3241 (95% CI = 1680, 20500) generations ago (81,000 years ago). These
      data suggest that these two polymorphisms in the HLA-G gene have had different
      evolutionary histories. We propose that natural selection has acted on the
      1597DeltaC allele.

PMID- 11975983
TI  - A study on CD45 isoform expression during T-cell development and selection events
      in the human thymus.
AB  - CD45 molecules are known to appear as various isoforms generated by alternative
      splicing of variable exons 4, 5, and 6, but the detailed profile of CD45 isoform
      expression during thymocyte development has not been revealed. We examined the
      CD45 isoforms expressed in the various human thymocytes' subsets defined by CD3,
      CD4, and CD8 expressions using RT-PCR and 4-color flow cytometry. RT-PCR study
      revealed that RABC, RAB, RBC, RB, and R0 isoforms were expressed in thymocytes
      while any of RAC, RA, or RC isoforms were not detected. RABC, RAB and RBC
      isoforms were expressed at CD3(-)CD4(-)CD8(-) and CD3(+)CD4(+)CD8(-) stages, but
      were barely detectable at CD3(-)CD4(+)CD8(+) stage. RB isoform was consistently
      expressed at a relatively high level at all stages. R0 isoform was expressed at a
      low level at CD3(-)CD4(-)CD8(-) and CD3(-)CD4(+)CD8(-) stages but upregulated at
      CD3(+)CD4(+)CD8(+) and CD3(+)CD4(+)CD8(-) stages. In combination with the results
      obtained by 4-color flow cytometric study, CD45 isoform expression on human
      thymocytes were determined to be RABC(+)RAB(+/-)RBC(+)RB(+)R0(+/-) at CD3(-)CD4(
      )CD8(-) stage, RABC(-)RAB(-)RBC(-)RB(+)R0(+) at CD3(-)CD4(+)CD8(-) and CD3(
      )CD4(+)CD8(+) stages, RABC(+/-)RAB(+)RBC(+)RB(++)R0(++) at CD3(+)CD4(+)CD8(+)
      stage, and RABC(+)RAB(+)RBC(+)RB(++)R0(+) at CD3(+)CD4(+)CD8(-) stage. Bcl-2
      expression was upregulated between CD3(-)CD4(+)CD8(+)CD45R0(+) and
      CD3(+)CD4(+)CD8(+)CD45R0(+) stages. Expression of CD45R0 epitope was upregulated
      between CD3(-)CD4(+)CD8(+)CD69(-) and CD3(+)CD4(+)CD8(+)CD69(+) stages while
      CD45RA epitope expression was unchanged. Thus, when thymocytes are positively
      selected, CD45R0 isoform expression seems to be upregulated while CD45RABC
      isoform expression stays at a very low level. In summary, various isoforms of
      CD45 were shown to be tightly regulated during thymocyte development and through
      the selection process.

PMID- 11975985
TI  - Analysis of the role of DPB1-encoded amino acids in the genetic predisposition to
      type I diabetes mellitus.
AB  - The role of the DPB1 gene in genetic susceptibility to type I diabetes has yet to
      be elucidated. Studies of DPB1 alleles are conflicting. Analysis at the amino
      acid level, rather than consideration of allelic polymorphism, has been
      informative in determining disease susceptibility encoded by the DRB1 and DQ
      genes. In this study, therefore, amino acid variation at polymorphic sites of the
      DPbeta peptide chain encoded by the second exon of the DPB1 gene was analyzed in
      diabetic and control subjects from white Caucasian, North Indian Asian, and
      Jamaican populations. Human leukocyte antigen genotypes and haplotypes were
      analyzed using a logistic-regression approach and the data were conditioned for
      the effects on disease risk of the DRB1, DQA1, and DQB1 genes. Eight DPbeta amino
      acid residues were significantly associated with type I diabetes independent of
      DR and DQ (DPbeta 9, 33, 35, 36, 55, 56, 57, and 69). None of these residues,
      however, correlated consistently with disease risk in all three racial groups.
      This contrasts with findings for the DRbeta, DQalpha and DQbeta peptide chains,
      where the identity of the amino acid at particular sites has been found to
      correlate with predisposition to type I diabetes.

PMID- 11975986
TI  - Major histocompatibility complex class I chain related (MIC) A gene, TNFa
      microsatellite alleles and TNFB alleles in juvenile idiopathic arthritis patients
      from Latvia.
AB  - In order to analyze involvement of major histocompatibility complex class I chain
      related gene A (MICA) and tumor necrosis factor a (TNFa) microsatellite
      polymorphisms as well as TNFB gene in juvenile idiopathic arthritis (JIA), we
      studied 128 patients divided into groups according to clinical features
      [monoarthritis (n = 14), oligoarthritis (n = 58), polyarthritis (n = 50), and
      systemic (n = 6)], and 114 age- and sex-matched healthy controls from Latvia. DNA
      samples were amplified with specific primers and used for genotyping of MICA and
      TNFa microsatellite. Typing for a biallelic NcoI polymerase chain reaction RFLP
      polymorphism located at the first intron of TNFB gene was done as follows:
      restriction digests generated fragments of 555bp and 185bp for TNFB*1 allele, and
      740bp for TNFB*2 allele. The results were compared between cases and controls. We
      found significant increase of MICA allele A4 (p = 0.009; odds ratio [OR] = 2.3)
      and allele TNFa2 (p = 0.0001; OR = 4.4) in patients compared with controls. The
      frequency of allele TNFa9 was significantly decreased (p = 0.0001; OR = 0.1) in
      patients with JIA. No significant differences of TNFB allele frequency were
      found. Our data suggest that MICA and TNFa microsatellite polymorphisms may be
      used as markers for determination of susceptibility and protection from JIA.

PMID- 11975987
TI  - Central MHC genes affect IgA levels in the human: reciprocal effects in IgA
      deficiency and IgA nephropathy.
AB  - This study investigates the hypothesis that alternative alleles of one or more
      genes in the central major histocompatibility complex (MHC) predispose carriers
      to IgA deficiency (IgAD) or IgA Nephropathy (IgAN). Australian caucasian IgAD,
      IgAN patients, and controls were typed at HLA loci, single nucleotide
      polymorphisms, and microsatellites in the MHC. Alleles of the D6S273
      microsatellite exhibited strong associations with IgAD and IgAN. D6S273*129 and
      *139 were more frequent in IgAD and less frequent in IgAN patients than controls.
      The reverse was true for D6S273*133 and *131. Alleles of other microsatellites
      exhibited weak associations with IgAD or IgAN. D6S273*129 is found on the 65.1
      ancestral haplotype [HLA-B14(65),DR1], which has been reported to be increased in
      IgAD, but the majority of IgAD patients with D6S273*129 did not have other
      alleles of the haplotype. D6S273*139 is characteristic of the 8.1 ancestral
      haplotype (HLA-A1,B8,DR3), which was common in IgAD and rare in IgAN patients.
      Further studies of the 8.1 haplotype in Australian, German and Spanish caucasian
      subjects revealed that HLA-DR3, in the absence of -B8, is not associated with
      IgAD. However -B8 is associated with IgAD in the absence of -DR3, consistent with
      a susceptibility locus in the central MHC. Provisional mapping within this region
      is discussed.

PMID- 11975988
TI  - Nomenclature for factors of the HLA system, update January 2002.

PMID- 11975989
TI  - The nature of the receptor site for the reversible K+ channel blocking by
      aminopyridines.
AB  - This work presents a theoretical study aimed at the identification of the
      receptor site for the blocking of the voltage dependent K+ channels by protonated
      aminopyridines. Thus, the density functional theory (DFT) at the B3LYP/6-311 G
      (d,p) level is applied, both in vacuum and in solution, to a series of active
      (protonated) compounds: 2-aminopyridine, 3-aminopyridine, 4-aminopyridine, 3,4
      diaminopyridine, and 4-aminoquinoleine. Analysis of the X-ray structure of the
      alpha-subunit of the channel shows that charged aminopyridines can interact
      electrostatically with a glutamic acid residue in the outside of the pore, or
      through a cation-pi interaction in the inside. To test both possibilities, model
      complexes are built using as nucleophiles a carboxylic group and an ethylene
      molecule, respectively. The three-dimensional electrostatic potential
      distribution of the protonated aminopyridines shows that an approaching
      nucleophile will be oriented toward the N-H (protonated) bond. Interaction with
      the carboxylic residue leads to a proton transfer, with the aminopyridine
      carboxylic acid linked by a hydrogen bond. The observed breaking of the
      equivalence of the Laplacian of the charge density, the relative energy variation
      for the complexes, and the interaction with only one of the carboxylic residues
      in the fourfold alpha-subunit of the K+ channel are not compatible with the
      observed in vitro activity variation of aminopyridines. On the other hand, the
      study on the ethylene complexes shows, in vacuum and solution, a cation-pi
      interaction, clearly characterized by the atoms in molecules (AIM) theory. The
      variation of relative energy in solution is very small, but approaches the
      variation of in vitro activity. Our results, the pharmacophoric characteristics
      of aminopyridines, and the analysis of the three-dimensional internal structure
      of the K+ channel alpha-subunit suggest two putative receptor sites. One is
      formed by the four Thr-Thr-Val chains conforming the entrance to the narrow part
      of the inner K+ channel. The other is defined by four Thr residues within the
      pore.

PMID- 11975990
TI  - Charge transfer between tryptophan and tyrosine in casein: a pulse radiolysis
      study.
AB  - Charge transfer from tyrosine to tryptophan radicals in bovine milk casein, as
      observed using pulse radiolysis technique, is reported. The reactions of casein
      with hydroxyl, azide, Br(2)(*-) and CCl(3)O(2)(*) radicals have also been
      studied. Radical transformation was found to take place at a rate of 1.5 x10(4)
      s(-1). The effect of pH, oxidising radical and the proximity of tyrosine and
      tryptophan on this radical transformation, as well as repair of the casein
      radical by ascorbate, have also been studied.

PMID- 11975991
TI  - Parallel activation in the ATP supply-demand system lessens the impact of inborn
      enzyme deficiencies, inhibitors, poisons or substrate shortage on oxidative
      phosphorylation in vivo.
AB  - A potential kinetic impact of parallel activation of different steps during an
      increased energy demand on the effect of inborn enzyme deficiencies,
      physiological inhibitors, external poisons and substrate shortage on oxidative
      phosphorylation was studied in the theoretical way. Numerical simulations were
      performed with the aid of the previously developed computer model of oxidative
      phosphorylation. It was demonstrated that the parallel activation mechanism
      diminishes significantly changes in fluxes and metabolite concentrations
      occurring at a given degree of inactivation of the system by one of the above
      mentioned factors. It was also shown that parallel activation decreases greatly
      the threshold value of the relative activity of oxidative phosphorylation, below
      which the oxygen consumption flux and ATP turnover flux become significantly
      affected. Finally, computer simulations predicted that parallel activation leads
      to a considerable increase in the apparent affinity of oxidative phosphorylation
      to oxygen, which delays the effect of inhibitors and poisons competing with
      oxygen for the active centre of cytochrome oxidase. It is concluded that one of
      possible functions of parallel direct activation of different steps of oxidative
      phosphorylation is to increase the resistance of the system to a decrease in the
      concentration/activity of different oxidative phosphorylation complexes.

PMID- 11975992
TI  - Thermodynamics of reactions catalyzed by PABA synthase.
AB  - Microcalorimetry and high-performance liquid chromatography (HPLC) have been used
      to conduct a thermodynamic investigation of reactions catalyzed by PABA synthase,
      the enzyme located at the first step in the shikimic acid metabolic pathway
      leading from chorismate to 4-aminobenzoate (PABA). The overall biochemical
      reaction catalyzed by the PabB and PabC components of PABA synthase is:
      chorismate(aq)+ammonia(aq)=4-aminobenzoate(aq)+pyruvate(aq)+H(2)O(l). This
      reaction can be divided into two partial reactions involving the intermediate 4
      amino-4-deoxychorismate (ADC): chorismate(aq)+ammonia(aq)=ADC(aq)+H(2)O(l) and
      ADC(aq)=4-aminobenzoate(aq)+pyruvate(aq). Microcalorimetric measurements were
      performed on all three of these reactions at a temperature of 298.15 K and pH
      values in the range 8.72-8.77. Equilibrium measurements were performed on the
      first partial (ADC synthase) reaction at T=298.15 K and at pH=8.78. The
      saturation molality of 4-aminobenzoate(cr) in water is (0.00382+/-0.0004) mol kg(
      1) at T=298.15 K. The results of the equilibrium and calorimetric measurements
      were analyzed in terms of a chemical equilibrium model that accounts for the
      multiplicity of ionic states of the reactants and products. These calculations
      gave thermodynamic quantities at the temperature 298.15 K and an ionic strength
      of zero for chemical reference reactions involving specific ionic forms. For the
      reaction: chorismate(2-)(aq)+NH(4)(+)(aq)=ADC(-)(aq)+H(2)O(l), K=(10.8+/-4.2) and
      Delta(r)H(m)(o)=-(35+/-15) kJ mol(-1). For the reaction: ADC(-)(aq)=4
      aminobenzoate(-)(aq)+pyruvate(-)(aq)+H(+)(aq), Delta(r)H(m)(o)=-(139+/-23) kJ
      mol(-1). For the reaction: chorismate(2-)(aq)+NH(4)(+)(aq)=4-aminobenzoate(
      )(aq)+pyruvate(-)(aq)+H(2)O(l)+H(+)(aq), Delta(r)H(m)(o)=-(174+/-6) kJ mol(-1).
      Thermodynamic cycle calculations were used to calculate thermodynamic quantities
      for three additional reactions that utilize L-glutamine rather than ammonia and
      that are pertinent to this branch point of the shikimic acid pathway. The
      quantities obtained in this study permit the calculation of the position of
      equilibrium of these reactions as a function of temperature, pH, and ionic
      strength. Values of the apparent equilibrium constants and the standard
      transformed Gibbs energy changes Delta(r)G'(m)(o) under approximately
      physiological conditions are given.

PMID- 11975993
TI  - Interactions of the DNA intercalator acridine orange, with itself, with caffeine,
      and with double stranded DNA.
AB  - Caffeine (CAF) inhibits the intercalation of acridine orange (AO) into cellular
      DNA. Optical absorption and fluorescence spectroscopy were employed to determine
      the molecular interactions of AO with itself, with CAF, and with double stranded
      herring sperm DNA (dsDNA). AO dimerization was observed at concentrations >2
      micromol. The sharp increase in fluorescence (lambda(em)=530 nm) at 5 micromol of
      AO was attributed to AO multimer formation. From 0.5 to 5.0 micromol, the AO self
      association binding constant (K(assoc)) was determined to be 38620 mol(-1),
      however, the presence of 150 mmol NaCl increased K(assoc) to 118000 mol(-1)
      attributed to the charge neutralization. The K(assoc) for AO with CAF was
      confirmed to be 256 mol(-1). K(assoc) for the binding of AO with 20 micromol DNA
      ranged from, 32000 mol(-1) at 2 micromol AO, to approximately 3700 mol(-1) at 10
      micromol AO, in the absence of NaCl. This AO concentration dependency of K(assoc)
      value with DNA was attributed to AO intercalation into dsDNA at high dsDNA/AO
      ratios, and electrostatic binding of AO to dsDNA at low AO ratios. The findings
      provide information used to explain fluorescence intensity values at lambda(em)
      at 530 nm from studies that combine AO, caffeine, and dsDNA.

PMID- 11975994
TI  - Effects of photoproducts on the binding properties of protoporphyrin IX to
      proteins.
AB  - Photosensitisers are the photoactive molecules used in photodynamic therapy (PDT)
      of cancer. Despite the importance of their interaction with polypeptides, only
      the binding to plasma proteins has been investigated in some detail. In our study
      we compared the binding of Protoporphyrin IX (a clinically useful
      photosensitiser) to an immunoglobulin G, with the binding to albumins. Binding to
      IgG is relevant because a possible method of increasing tumour specificity of
      photosensitisers is to bind them to tumour-specific antibodies. Binding constants
      to albumins and the immunoglobulin were comparable ( congruent with6 x 10(-6) M(
      1)). The apparent number of PPIX molecules bound to each protein was also within
      a similar range (from 4 to 7). The absence of a shift in the emission spectrum of
      PPIX bound to IgG, however, indicates that either larger aggregates of PPIX bind
      to the immunoglobulin or that the binding site leaves PPIX exposed to the buffer.
      We observed that PPIX photoproducts compete with PPIX for the same binding sites.
      The number of PPIX molecules bound to each protein in the presence of
      photoproducts decreased by 50-80%. Due to the spectral overlap between PPIX and
      its photoproducts, the binding in the presence of photoproducts was investigated
      using Derivative Synchronous Fluorescence Spectroscopy (DSFS) to improve the
      spectral separation between chromophores in solution. We also concluded that
      fluorescence measurements underestimate the number of PPIX molecules binding each
      protein. In fact, non-linear Scatchard plots (in the case of albumin binding) by
      definition yield a minimum number of molecules attached to a protein. Moreover,
      the binding of large aggregates, formed by an unknown number of PPIX molecules,
      to IgG results in the underestimate of the number of molecules bound. The number
      of PPIX molecules bound to these proteins is also much larger than the number of
      sites estimated by protein fluorescence quenching.

PMID- 11975995
TI  - Analysis of the steam injection at the Visalia Superfund Project with fully
      compositional nonisothermal finite difference simulations.
AB  - By injecting steam, over 1.1 million pounds of creosote has been recovered at the
      Visalia, California Superfund Site from an aquifer 102ft underground. In the
      first 6 weeks of injection 320,000lb of creosote were recovered or destroyed
      versus <1lb per day in a pump and treat. The finite difference simulator STARS1,
      which is widely used in the oil industry to model thermal recovery, has been used
      to simulate simplified models of the project, to analyze recovery mechanisms, and
      to demonstrate how the operation of similar projects can be improved. The
      simulations indicate that vaporization of dense, nonaqueous, phase liquids
      (DNAPLs) is the most important recovery mechanism, that liquid production is
      enhanced because a gas phase is present, and that the project could have been
      completed more rapidly if an additional injector or producer had been added in
      the center of the site. In addition, the mineralization (conversion to carbon
      dioxide) of DNAPLs could result from reaction with water, injected air or, most
      likely, both. The mechanisms are likely to be similar to subcritical water
      oxidation. While this analysis suggests methods to improve operation of future
      steam projects, Visalia has been a very successful demonstration of the potential
      of steam injection to clean up recalcitrant hydrocarbons and will be an
      inspiration for future projects.

PMID- 11975996
TI  - Membrane-based hybrid processes for high water recovery and selective inorganic
      pollutant separation.
AB  - The removal of heavy metals (e.g. Pb(II), Cd(II), Cu(II), etc.) and oxyanions
      (e.g. nitrate, As(III, V), Cr(VI), etc.) is of immense interest for treatment of
      groundwater and other dilute aqueous systems. However, the presence of non-toxic
      components, such as hardness (Ca, Mg) and sulfate, can interfere with the
      separation of toxic species. For example, pressure-driven membrane processes,
      such as reverse osmosis (RO), have been limited for water treatment due to
      problems that these extraneous components cause with water recovery and ionic
      strength (osmotic pressure) of the retentate. In addition, nitrate rejection by
      RO is considerably lower than NaCl rejection, resulting in permeate
      concentrations that may be too high for groundwater recharging. Other separation
      systems that rely solely on sorption of toxic species (e.g. ion exchange resins)
      may not have sufficient selectivity for efficient use in the presence of
      competing ions. Hence, implementation of pressure-driven membrane separations and
      high capacity sorbents in hybrid processes shows much promise for remedying these
      difficulties. For example, selective separation of nitrate may be achieved by
      combining nanofiltration (NF) for sulfate removal, followed by RO or ion exchange
      for nitrate removal (see example 1). When small concentrations of toxic metals
      are present, the large retentate volumes of RO processes may be reduced by
      selective removal of toxic species with a high capacity sorbent, thus permitting
      disposal of a lower volume, non-toxic stream (see example 2). The use of
      microfiltration membrane-based sorbents containing multiple polymeric functional
      groups is a novel technique to achieve high metal sorption capacity under
      convective flow conditions. These sorbents are formed by the attachment of
      various polyamino acids (MW: 2500-10,000), such as polyaspartic acid (cation
      sorption), polyarginine (oxyanion sorption), and polycysteine (chelation
      exchange), directly on the membrane pore surfaces. Since these sorbents have also
      been found to have high selectivity over non-toxic metals, such as calcium, they
      are ideal candidates for hybrid processing with RO/NF.

PMID- 11975997
TI  - Comparing the performance of various advanced oxidation processes for treatment
      of acetone contaminated water.
AB  - Removal of low levels of organic pollutants can be quite challenging to many
      water treatment processes. Ketones, such as acetone, are often found in
      groundwaters and wastewaters at levels too low for supporting a bioreactor, yet
      since acetone is so soluble, it does not adsorb onto activated carbon very well,
      nor does it volatilize from water influent using air stripping. This study was
      undertaken to evaluate three advanced oxidation processes for their comparative
      ability to remove acetone from aqueous media. Optimization of the oxidation
      processes was attempted via adjustments of oxidizer inputs. The results indicated
      that all of the AOPs tested showed promise for removing acetone from water;
      however, ozonated systems undergoing UV photolysis achieved the highest rate and
      extent of treatment observed.

PMID- 11975998
TI  - Dechlorination of PCBs, CAHs, herbicides and pesticides neat and in soils at 25
      degrees C using Na/NH3.
AB  - Na/NH3 reductions have been used to dehalogenate polychlorinated biphenyls
      (PCBs), chlorinated aliphatic hydrocarbons (CAHs) and pesticides at diffusion
      controlled rates at room temperature in model compound studies in both dry NH3
      and when water was added. The rate ratio of dechlorination (aliphatic and
      aromatic compounds) versus reaction of the solvated electron with water is very
      large, allowing wet soils or sludges to be remediated without an unreasonable
      consumption of sodium. Several soils, purposely contaminated with 1,1,1
      trichloroethane, 1-chlorooctane and tetrachloroethylene, were remediated by
      slurring the soils in NH3 followed by addition of sodium. The consumption of
      sodium per mole of chlorine removed was examined as a function of both the
      hazardous substrate's concentration in the soil and the amount of water present.
      The Na consumption per Cl removed increases as the amount of water increases and
      as the substrate concentration in soil decreases. However, remediation was still
      readily accomplished from 5000 to 3000ppm to sub ppm levels of RCl in the
      presence of substantial amounts of water. PCB- and dioxin-contaminated oils were
      remediated with Na/NH3 as were PCB-contaminated soils and sludges from
      contaminated sites. Ca/NH3 treatments also successfully remediated PCB
      contaminated clay, sandy and organic soils but laboratory studies demonstrated
      that Ca was less efficient than Na when substantial amounts of water were
      present. The advantages of solvated electron reductions using Na/NH3 include: (1)
      very rapid dehalogenation rates at ambient temperature, (2) soils (even clay
      soils) break down into particles and slurry nicely in NH3, (3) liquid ammonia
      handling technology is well known and (4) removal from soils, recovery and
      recycle of ammonia is easy due to its low boiling point. Finally, dechlorination
      is extremely fast even for the 'corner' chlorines in the substrate Mirex
      (structure in Eq. (5)).

PMID- 11975999
TI  - Reduction of suspended solids following hydroclassification of metal-contaminated
      soils.
AB  - Remediation of metals-contaminated soil typically uses
      solidification/stabilization and "dig and haul". Soil washing and physical
      separation have been applied to a much lesser extent to reduce soil volumes
      requiring aggressive treatment and to improve performance of follow-up
      treatments. In earlier work [J. Hazard. Mater. 66 (1999) 15], we used a simple,
      vertical-column hydroclassifier, to separate four soils contaminated with heavy
      metals, defining a "best case" performance for larger-scale (minerals processing)
      equipment. Such processes, using water-based slurries, generate substantial
      volumes of water with suspended solids. These typically contain
      disproportionately high concentrations of heavy metals. Here, we performed an
      initial screening of settling, coagulation, and centrifugation for reducing
      suspended solids, and thus suspended metals from soil slurries following
      processing. The four soils, previously hydroclassified, were sieved to <600
      microm, slurried with a 4:1 weight ratio of water, and allowed to settle. Slurry
      samples were collected at settling times of 0, 0.0833, 1, 5, and 22-24h.
      Coagulant (alum) addition and centrifugation were investigated. The slurries were
      filtered, digested, and analyzed by atomic absorption for lead and chromium
      content. Two soil slurries clarified in <5 min. In all four cases, 90% of solids
      and metals settled within 5h. However, completion may require up to 24h, or other
      intervention, i.e. coagulants. The metal concentration in the residual suspended
      solids increased with settling time, implying an enrichment of metals in finer,
      suspended particles. Metals dissolved in the slurry water ranged from 3 to 5mg/l
      for chromium and lead. This screening study provides guidance for water treatment
      requirements and treatability studies for the integration of hydroclassification
      and solids removal.

PMID- 11976000
TI  - Anaerobic treatment of pinkwater in a fluidized bed reactor containing GAC.
AB  - Pinkwater is generated during the handling and demilitarization of conventional
      explosives. This listed hazardous waste contains dissolved trinitrotoluene (TNT)
      and cyclo trimethylene trinitramine (RDX), as well as some by-products. It
      represents the largest quantity of hazardous waste generated by the operations
      support command, and its treatment produces a by-product hazardous waste--spent
      granular activated carbon (GAC). Anaerobic treatment in a fluidized bed reactor
      (FBR) containing GAC is an emerging technology for organic compounds resistant to
      aerobic biological treatment. Bench scale batch studies using an anaerobic
      consortium of bacteria fed ethanol as the sole electron donor demonstrated the
      transformation of TNT to triaminotoluene (TAT), which then degrades to
      undetectable end products. RDX is sequentially degraded to nitroso-, dinitroso-,
      trinitroso- and hydroxylaminodinitroso-RDX before the triazine ring is presumably
      cleaved, forming methanol and formaldehyde as major end products. The bacterial
      members of the anaerobic consortia are typically found in sludge digesters at
      municipal or industrial wastewater treatment plants. The results of a pilot scale
      evaluation of this process that was conducted at McAlester Army Ammunition Plant
      (MCAAP, OK) over a 1 year period are reported in this paper. The pilot test
      experienced wide fluctuations in influent concentrations, representative of true
      field conditions. The FBR was a 20 in. (51 cm) diameter column with an overall
      height of 15 ft (4.9 m) and a bed of GAC occupying 11 ft (3.4m). Water was
      recirculated through the column continuously at 30 gpm (114 l/min) to keep the
      GAC fluidized, and pinkwater for treatment was pumped into the recirculation
      line. Several flowrates were evaluated to determine the proper mass loading rate
      (mass of TNT and RDX per reactor volume per time, kg/m(3) per day) which the
      reactor could handle while meeting the discharge limitations. Based on the tests
      performed, a 1 gpm (3.785 l/min) rate in the 188 gal (710 l) volume of the
      fluidized GAC bed was determined to consistently meet the discharge requirements.
      This information was used to develop a cost estimate for a system capable of
      treating the total effluent currently produced at MCAAP. The cost of installing
      and operating this system was compared to the cost of GAC adsorption for MCAAP at
      current pinkwater generation rates. The GAC-FBR system had an annual operating
      cost of approximately US$ 19K, compared to US$ 71 K annually for GAC adsorption.
      When including the amortization of the capital equipment required for the GAC
      FBR, the payback period for installation of this new process was estimated at 3.7
      years.

PMID- 11976001
TI  - Effects of n-hexadecane and PM-100 clay on trichloroethylene degradation by
      Burkholderia cepacia.
AB  - Trichloroethylene (TCE) is a non-flammable, volatile organochlorine compound
      which was a widely used degreasing agent, anesthetic, and coolant prior to 1960,
      but has since been placed on the Environmental Protection Agency's (EPA) list of
      priority pollutants. The inadequate disposal practices for TCE have created
      numerous TCE-contaminated superfund sites. The most commonly employed practice
      for remediating TCE-contaminated sites is to purge the contaminant from the
      source and trap it onto an adsorbent which is disposed of in a landfill or by
      incineration. This investigation was undertaken to evaluate the effectiveness of
      Burkholderia cepacia strain G4 (G4) to regenerate used sorbents by degrading TCE
      from the sorbent directly or indirectly. The results of this investigation showed
      that G4 was capable of reducing TCE attached to PM-100 clay but at significantly
      reduced rate due to the slow desorption rate. Conversely, it was shown that G4
      was capable of degrading TCE dissolved in n-hexadecane at the same rate as
      systems without n-hexadecane present. The reduction in TCE degradation when the
      TCE is attached to the PM-100 clay could be overcome by solvent rinsing the TCE
      from the clay with subsequent removal of the TCE from the n-hexadecane by G4.

PMID- 11976002
TI  - Effect of food-grade surfactant on bioremediation of explosives-contaminated
      soil.
AB  - The use of native soil bacteria to biodegrade explosives-contaminated soil under
      co-metabolic conditions has been demonstrated. The addition of food-grade
      surfactants could improve the process by enhancing the rates of explosives
      desorption from soil, thereby increasing the bioavailability of explosives for
      microbial degradation. The objective of this study was to decrease residence time
      in the slurry reactor, thereby increasing output and reducing clean-up costs. In
      this study, Tween 80 (monooleate), served not only as a surfactant but also as
      the carbon substrate for the soil microorganisms. Four 2l soil slurry reactors
      were operated in batch mode with soil containing 2,4,6-trinitrotoluene (TNT) and
      hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The results indicated that TNT and
      RDX were removed in all reactors except the control (no added carbon source). The
      reactor enriched with surfactant and molasses performed better than reactors with
      either molasses or surfactant alone. The TNT and its metabolite, 4-amino-2,6
      dinitrotoluene were removed faster in the reactor with surfactant plus molasses
      (35 days) than in the reactor with molasses alone as carbon source (45 days). A
      radiolabeling study of the mass balance of TNT in the slurry reactors showed
      substantial mineralization of TNT to CO2.

PMID- 11976004
TI  - College on Problems of Drug Dependence 64th Annual Scientific Meeting. June 8-13,
      2002. Quebec City, Quebec, Canada. Abstracts.

PMID- 11976005
TI  - Spinal trauma.

PMID- 11976006
TI  - Spinal injury: optimising the imaging options.
AB  - There have been numerous documented attempts in formulating risk-based guidelines
      for the exclusion of spinal injury using conventional radiography. Although the
      advent of computed tomography (CT) (including spiral and multi-slice) and
      magnetic resonance imaging (MRI) confirmed the known limitations of conventional
      radiography, there is still a requirement to define optional use of these
      modalities in a trauma setting. This chapter addresses these issues by reviewing
      the literature and provides a synopsis of the current thinking in the appropriate
      sections (adult, paediatric, symptomatic, asymptomatic, etc.) in the quest of
      finding out the correct answers on how best to exclude/confirm spinal trauma.

PMID- 11976007
TI  - Malalignment: signs and significance.
AB  - Malalignment of the vertebrae, in patients suspected of blunt spinal trauma, is
      the quintessential sign of spinal injury. Malalignment is obvious in displaced
      fractures and dislocations but is rarely considered in the diagnosis because of
      the obvious injury. In patients with more subtle injuries such as those limited
      to ligamentous structures, vertebral malalignment is the only radiographic sign
      that leads one to the recognition of the injury. Equally important is the fact
      that vertebral malalignment may be congenital and may be due to physiologic
      movement as well as radiographic patient positioning. Recognition of the pattern
      of traumatic malalignment as distinguished from the appearance of non-traumatic
      malalignment is essential to accurate radiologic diagnosis. Because malalignment
      is critical to the radiographic assessment of blunt cervical spine injury, this
      presentation is limited to the cervical spine. The format of the article includes
      signs of physiologic and traumatic malaignment as seen on antero-posterior and
      lateral radiographs of the cervico-cranium and the lower cervical spine.

PMID- 11976008
TI  - Vertebral injuries: detection and implications.
AB  - Vertebral injuries occur in a predictable and reproducible manner that is
      dependent upon the mechanism of injury. Each mechanism of injury leaves distinct
      imaging 'fingerprints' regardless of the location in the spine. This chapter will
      discuss four areas: the mechanisms of injury and their imaging 'fingerprints';
      abnormalities of alignment and anatomy, bony integrity, cartilage or joint space,
      and soft tissues-the ABCS of injury; the imaging features that will indicate
      stability of the spine following injury; and the classification of spine injuries
      into two categories-'major' or 'minor'. The imaging features described in this
      chapter apply to both radiography as well as to computed tomography (CT).
      Although helical CT is being used more commonly for the evaluation of suspected
      cervical injuries, radiography of the entire spine remains the standard.

PMID- 11976009
TI  - Neurovascular injuries of the spinal cord.
AB  - Neurovascular spinal cord injuries are very prevalent and in a busy trauma center
      radiology practice these injuries are commonly seen. Imaging neurovascular
      injuries has been greatly facilitated by magnetic resonance imaging (MRI) and
      magnetic resonance angiography (MRA). The histopathological changes that occur
      with spinal cord trauma have been found to correlate well with what is seen on
      MRI examinations. The MRI findings in spinal cord trauma have also been found to
      be useful in determining patient prognosis. Spinal cord infarcts due to arterial
      injury from trauma are relatively rare, but it has been shown by imaging that
      vertebral artery injuries are not an unusual occurrence. The specific findings
      associated with neurovascular injuries will be described with an emphasis on the
      findings on MRI and MRA examinations. MRI and MRA techniques have become the
      procedure of choice for evaluating neurovascular injuries because of their proven
      accuracy and because they are non-invasive. Conventional angiography, although,
      does remain quite useful for evaluating arterial injuries.

PMID- 11976010
TI  - Spinal trauma: therapy--options and outcomes.
AB  - The management of patients with spinal trauma is based on the following goals:
      (1) the preservation of life; (2) preserving and maximising the neurological
      function; and (3) providing a stable, painless vertebral column. There have been
      advances in both non operative as well operative modalities of treatment of
      patients with spinal injuries. These advances have led to renewed interest in the
      management of a spinally injured patient. However, despite these advances
      controversies exist regarding the classification of these fractures, the use of
      pharmacological intervention, the timing of surgical intervention and indeed the
      use of surgical intervention itself in the management of these fractures. Most of
      these controversies surround the treatment of thoracic and lumbar fractures. The
      purpose of this article is to provide an over view of the therapy options
      available in the treatment of these fractures. The article shall also look at
      some of the controversies surrounding the management of these fractures.

PMID- 11976011
TI  - Imaging in chronic spinal cord injury--indications and benefits.
AB  - As most patients who have suffered spinal cord injury can now expect a normal
      life span, the late complications of these injuries are seen increasingly
      frequently. Regular surveillance of both the renal tract and the central nervous
      system (CNS) is important as the treatment of impending, potentially fatal
      complications can be implemented before damage has progressed too far. Renal
      tract complications are particularly dangerous as they are often clinically
      silent but regular surveillance to detect early deterioration in renal function,
      particularly from reversible causes such as reflux or obstruction can pre-empt
      problems. Follow-up protocols depend on the bladder management regime but most
      centres advocate regular ultrasound with less frequent isotope function studies.
      With the increasing ability to diagnose and treat the neurological complications,
      surveillance of the state of the spinal cord with MRI is also important and many
      centres now advocate checks every few years with sagittal midline T2W sections
      are sufficient unless changes are noted, when axial T1W sections can be added
      without significant examination time penalty. Imaging is critical in acute
      problems. In addition to suffering from the usual normal conditions, patients
      with spinal cord injury suffer others peculiar to, or particularly related to,
      the injury, which may be missed as their symptomatology is greatly altered by
      their paraplegic or quadriplegic status and they may often present as generally
      unwell but with no obvious cause. This review discusses the role of radiology in
      routine surveillance of the CNS and the renal tract as well as in assessing
      specific conditions such as deteriorating neurology or renal function, pain,
      spinal instability, pressure sores, ectopic ossification, muscular spasm, spinal
      instability, airway problems and elective operations on the renal tract.

PMID- 11976012
TI  - MRI assessment of post-traumatic spinal instability.
AB  - The imaging evaluation of patients with spinal trauma has evolved over the past
      decades, and there has been particular interest in the concept of instability, to
      predict which a series of criteria have been proposed. We retrospectively
      evaluated the magnetic resonance imaging (MRI) findings in 50 patients with post
      traumatic spinal instability according to Denis's three-column method, Daffner et
      al.'s radiographic criteria, and Oner et al.'s categorization of MRI findings;
      additionally, we evaluated the cord, the prevertebral tissue, and the epidural
      space. We suggest that an integrated panel of MRI information might be
      standardized in order to provide a more complete evaluation of spinal injury in
      an individual case and help planning surgical treatment.

PMID- 11976013
TI  - Therapeutic applications of microbubbles.
AB  - Microbubbles, currently used as contrast agents have potential therapeutic
      applications. Microbubbles, upon insonation of sufficiently intense ultrasound
      will cavitate. Cavitation with microbubbles can be used to dissolve blood clots
      or deliver drugs. Targeting ligands and drugs can be incorporated into
      microbubbles to make highly specific diagnostic and therapeutic agents for
      activation with ultrasound. In this paper I will review some of these potential
      applications and experimental results using such agents for thrombolysis, drug
      and gene delivery.

PMID- 11976014
TI  - Ocular tolerance of preservatives and alternatives.
AB  - Eye drops are multiple dosage forms protected against microbial contamination by
      means of preservatives. However, the ocular tolerance of these chemicals can vary
      and this may result in adverse toxic or allergic reactions. This overview
      presents the pharmacopoeial requirements for the preservation of eye drops, the
      factors affecting ocular tolerance as well as the adverse external ocular effects
      induced by preservatives. The alternatives to the use of preservatives are also
      discussed, including the recent progress in eye drops packaging.

PMID- 11976015
TI  - Comparative permeation studies for delta-aminolevulinic acid and its n-butylester
      through stratum corneum and artificial skin constructs.
AB  - The improvement of the permeation properties through excised human stratum
      corneum and artificial skin constructs (ASC) of delta-aminolevulinic-n-butylester
      (ABE) compared with delta-aminolevulinic acid (ALA) was investigated. For this
      purpose the permeated amounts of each substance were determined depending on time
      in a Franz diffusion cell experiment with stratum corneum and ASC, respectively.
      Furthermore the barrier properties of ASC were compared with those of stratum
      corneum. Detection of both substances was performed by high-performance liquid
      chromatography (HPLC) analysis. For the determination of ABE a new HPLC method
      was developed. ABE could be determined with the new HPLC method with sufficient
      sensitivity (detection limit: 0.1 microg/ml) after derivatisation with o
      phthalaldehyde (OPA). Stratum corneum and ASC were more permeable for ABE than
      for ALA. The permeation coefficient P of ABE through stratum corneum was nearly
      ten-fold higher than that of ALA. Using ASC as permeation barrier the permeation
      coefficient of ABE was about 22-fold higher than that of ALA. ABE and ALA
      permeated 142-fold and 64-fold, respectively, faster through ASC than through
      stratum corneum.

PMID- 11976016
TI  - A quantitative evaluation of radiolabelled lectin retention on oral mucosa in
      vitro and in vivo.
AB  - Previous work has identified lectins that bind to the cells present on the oral
      mucosa for their potential use as a means of retaining a drug delivery system on
      the mucosal surfaces of the mouth. In this study, a radiolabelling technique was
      developed to allow the quantification of lectin binding to human buccal cells in
      vitro, and the retention of the lectins in the oral cavity of a rat model in
      vivo. Lectins were labelled with 99mTc using a cyclic diethylene triamine
      pentaacetic acid conjugation technique. In the in vitro study, human buccal cells
      were obtained by scraping the inner surface of the cheek. The suspended cells
      were exposed to the labelled lectin solution for 30 min and after washing with
      buffer the activity associated with the cells determined. In the in vivo study,
      male Wistar rats were briefly anaesthetized during which 10 microl of a solution
      containing labelled lectin was applied into the buccal pouch. At set times the
      rats were killed and the lower buccal cavity mucosal tissue and tongue dissected
      out and monitored for bound lectin. The in vitro study indicated that the lectins
      from Arachis Hypogaea, Canavalia ensiformis and Triticum vulgaris bound to oral
      mucosal cells. The T. vulgaris lectin showed the greatest binding, calculated to
      be 6.77 x 10(9) molecules per cell. The in vivo retention of C. ensiformis and T.
      vulgaris lectins on rat oral mucosal tissue was also evident. The T. vulgaris
      lectin showed significantly higher levels of retained lectin after 30 min (29.54
      +/- 4.20 microg SD) on the oral mucosal tissue and 28.37 microg (+/-2.13 SD) on
      the tongue and was still detected at similar levels after 2 h. These studies
      indicate that significant lectin binding to human buccal cells occurs in vitro
      and retention in an animal model occurs for over 2 h in vivo. The T. vulgaris
      lectin showed most promise for further work.

PMID- 11976018
TI  - The influence of first pass metabolism on the development and validation of an
      IVIVC for metoprolol extended release tablets.
AB  - To investigate the influence of alpha-hydroxymetoprolol (AHM) and 4-(2-hydroxy-3
      isopropylaminopropoxy)-phenylacetic acid (ACMB), both derived from its first pass
      metabolism of metoprolol, an in vitro in vivo correlation incorporating first
      pass metabolite data for metoprolol extended release formulations was developed.
      Three different releasing formulations (slow (S), moderate (M) and fast (F), 100
      mg) of metoprolol were evaluated in a previously reported clinical study. The non
      first pass effect (Non-FPE) in vitro in vivo correlation (IVIVC) was developed
      using a fraction of metoprolol dissolved and a fraction of total drug (metoprolol
      + metabolites) as the absorption data for various combinations of formulations
      (S/M/F, M/F, S/M, and S/F). Direct convolution approaches predicting metoprolol
      concentrations and indirect convolution predicting total drug concentrations
      (metoprolol + metabolites) were used to determine in vivo behavior. The Non-FPE
      IVIVC using the S/M/F formulations displayed the strongest relationship (r2 >
      0.92). The IVIVC using the indirect approach was predictive of both the C(max)
      (prediction errors (PE) 4.77, 3.94 and 6.14%) and AUC (10.7, 11.0 and 11.3%) for
      metoprolol, AHM and ACMB. Poor predictability (PE > 40% for C(max) and AUC) was
      observed for metoprolol when using the direct methods. The predictability of the
      IVIVC using the indirect approach as compared to the direct method displays the
      influence of first pass metabolism on the development and evaluation of an IVIVC
      for a drug that displays a high extraction ratio. In addition, the indirect IVIVC
      allows for not only predicting the in vivo performance of the parent drug but
      also the metabolites formed via the first pass effect.

PMID- 11976020
TI  - A novel approach to determining physicochemical and absorption properties of 6
      fluoroquinolone derivatives: experimental assessment.
AB  - The ToSS MoDe approach is used to estimate the n-octanol/buffer partition
      coefficient, the apparent intestinal absorption rate constant and intestinal
      permeability from a 6-fluoroquinolone data set. Improved in silico methods for
      predicting a drug's ability to be transported across biological membranes and
      other biopharmaceutical properties is highly desirable to optimize new drug
      development. The physicochemical property (Log P) of 26 6-fluoroquinolone
      derivatives and the absorption properties (Log K(a) and Log P(eff)) of 21
      derivatives were well described by the present approach. The models obtained
      confirm the important role of lipophilicity in the absorption process and its
      relation with the piperazinyl ring spectral moment and general local spectral
      moment. The normalized group contributions to each property, at the R4 and R5
      positions of a 6-fluoroquinolone framework, were calculated. Principal factor
      analysis between these contributions and the Hammett and Hansch constant, molar
      refractivity and sterimol parameters was also carried out. Three principal
      factors explained 78% of the total variance and the correlation coefficients were
      higher than 0.98. The isocontribution zone analysis for the Log P and Log K(a) of
      Sarafloxacin and Sparfloxacin, used as external corroboration compounds, was
      carried out. The absorption rate constants (in situ rat gut technique) for these
      drugs were also evaluated, and the results were compared with the values
      predicted by theoretical models for evaluating predictive performance. The
      present approach proved to be a good method for studying the oral absorption of
      drug candidates in drug development studies.

PMID- 11976019
TI  - In vitro and in vivo study in rats of rectal suppositories containing furosemide.
AB  - The aim of our experimental work was to formulate furosemide-containing rectal
      suppositories, to study drug release with in vitro membrane diffusion
      examinations and to increase drug liberation with the use of non-ionic
      surfactants (Solutol HS 15, Cremophor RH 60, Montanox 60 DF), which were
      incorporated in the suppository base in various concentrations. Suppocire AS2X
      proved to be the best suppository base (diffused drug: 69.78%). The use of 1%
      Cremophor RH 60 additive with the Witepsol H 15 base increased the quantity of
      the diffused drug from 62 to 75%. The membrane diffusion examinations were
      followed by studying the influence of suppository bases and additives exerted on
      the actual diuretic effect in Sprague-Dawley male rats. Once again the Suppocire
      AS2X suppository base gave the best results compared to the control; the quantity
      of the animals' urine showed a fourfold increase. Used with the Witepsol H 15
      base, even 1% of all the three additives resulted in a considerable increase of
      diuretic effect, so their use proved to be advantageous. The comparison of the
      membrane diffusion examinations with the in vivo diuretic effect reveals that in
      vitro drug release and the pharmacological effect usually showed the same
      tendency, that is a greater extent of in vitro furosemide release was associated
      with a greater quantity of rat urine.

PMID- 11976017
TI  - Anti-cancer drug diffusion within living rat brain tissue: an experimental study
      using [3H](6)-5-fluorouracil-loaded PLGA microspheres.
AB  - This study was performed (i) to monitor the diffusion of the anti-cancer drug 5
      fluorouracil (5-FU) and (ii) to elucidate the fate of poly(lactide-co-glycolide)
      (PLGA) based microspheres within living rat brain tissue upon intracranial
      implantation. Drug-loaded microparticles were prepared using a solvent
      emulsion/extraction process and administered into healthy and C6 glioma-bearing
      Sprague-Dawley rats. The same surgical procedure was carried out with magnetite
      loaded microspheres. To monitor 5-FU diffusion from the implantation site, tissue
      combustion was performed on animals implanted with tritiated drug microspheres.
      T2-weighted nuclear magnetic resonance imaging was undertaken on animals
      implanted with magnetite-loaded microspheres to determine microsphere
      localization after deposit. Results show that an important microparticle backflow
      occurs in healthy rats, whereas the microspheres remain at the site of
      administration in C6 glioma-bearing rats. Drug diffusion is limited to the
      vicinity of the implantation site.

PMID- 11976021
TI  - The influence of pellet shape and film coating on the filling of pellets into
      hard shell capsules.
AB  - Pellets of different shape, varying from spherical to cylindrical, were filled
      into hard shell capsules. When no film coat was applied, the pellets had not to
      be perfectly spherical in order to be filled reproducibly. An aspect ratio of 1.2
      or less appeared to be the threshold value. However, pronounced surface roughness
      hindered the filling process, and hence it appears necessary to monitor this
      parameter. After coating of the pellets with an ethylcellulose film, none of the
      batches could be filled to an acceptable standard, because electrostatic loading
      led to a blockage of the filling mechanism. However, the addition of 1% talcum
      powder was sufficient to remove all charges, and again filling became a function
      of the pellet shape, confirming the threshold aspect ratio value of 1.2.

PMID- 11976022
TI  - Factors influencing the entrapment of hydrophilic compounds in nanocapsules
      prepared by interfacial polymerisation of water-in-oil microemulsions.
AB  - This study demonstrates the effect of drug properties and method of loading
      (sorption and encapsulation) on entrapment within poly(alkyl cyanoacrylate)
      nanocapsules prepared by interfacial polymerisation of biocompatible water-in-oil
      microemulsions. For small molecular weight compounds (<1000 Da), entrapment
      efficiency is more dependent on charge of the compound than on the method used
      for entrapment. Entrapment efficiency within the negatively charged nanocapsules
      (zeta potential approximately -30 mV) was in the order cationic compound >
      neutral compound > anionic compound. Only minimal differences for entrapment
      efficiency were noted between sorption (addition of the compound 4 h after
      initiation of the polymerisation) and encapsulation (addition of the compound to
      microemulsion prior to polymerisation). For high molecular weight compounds, the
      method used for entrapment however, is very important. For hydrophilic
      macromolecules such as proteins, high entrapment efficiencies can only be
      achieved by encapsulation. Entrapment of such compounds seems to be independent
      of the net charge of the compound being encapsulated but depended on the
      molecular weight. For nanocapsules prepared by interfacial polymerisation of
      water-in-oil microemulsions, these findings are useful as a foundation in the
      development of nanocapsules with desired properties.

PMID- 11976023
TI  - Formulation of an oral dosage form utilizing the properties of cubic liquid
      crystalline phases of glyceryl monooleate.
AB  - Glyceryl monooleate is a Food and Drug Administration-approved food additive
      which has the ability to form various liquid crystalline phases in the presence
      of various amounts of water. The unique properties of the cubic liquid
      crystalline phase that result upon the presence of excess body fluids at body
      temperature were utilized to formulate an oral dosage form containing furosemide
      as the model drug. The aim was to develop a formula, which has both bioadhesive
      and sustained release properties of the resultant cubic phase, so that increasing
      gastric residence time to improve bioavailability of the drug and at the same
      time obtaining a sustained action. The system was found to be affected by the
      limited solubility of furosemide in both the carrier system and the pH of
      surrounding medium. As a consequence, the addition of some solubility modifiers
      was investigated in order to obtain the desired properties of the expected liquid
      crystalline system.

PMID- 11976028
TI  - A new symmetrized solution for phase retrieval using the transport of intensity
      equation.
AB  - We propose a novel symmetrization method for solving the transport of intensity
      equation (TIE) using fast Fourier transforms for situations where the input
      images may or may not exhibit spatial periodicity. The method is derived from the
      analysis of intensity conservation law and the internal symmetry of the TIE, and
      is illustrated for both a computational and an experimental data set.

PMID- 11976024
TI  - Distribution of crushing strength of tablets.
AB  - The distribution of a given set of data is important since most parametric
      statistical tests are based on the assumption that the studied data are normal
      distributed. In analysis of fracture mechanics the Weibull distribution is widely
      used and the derived Weibull modulus is interpreted as a material constant.
      However, the estimation of this parameter is laborious and subject to estimation
      problems. It is shown that the Weibull modulus is inherently connected to the
      coefficient of variation and that the information obtained from the modulus is
      unclear. The distribution of crushing strength data from nine model tablet
      formulations and four commercial tablets are shown to follow the normal
      distribution. The importance of proper cleaning of the crushing strength
      apparatus is demonstrated.

PMID- 11976029
TI  - The female gonad of the epizoic platyhelminth Troglocaridicola sp. (Rhabdocoela,
      Temnocephalida, Scutariellidae): ultrastructural and cytochemical investigations.
AB  - The cytoarchitecture of the female gonad of the scutariellid Troglocaridicola sp.
      has been investigated by means of electron microscopy and cytochemical
      techniques. It consists of a single germarium and two rows of vitelline
      follicles, both enveloped by an outer extracellular lamina (EL) and an inner
      cellular tunica constituted by accessory cells. Some ultrastructural features
      which differ from the basic pattern of all the other Rhabdocoela studied so far
      have been found. In the germarium the following are observed: (a) The presence in
      the oocytes of peripheral translucent vesicles containing glycoproteins, which
      differ in diameter and substructure from the peripheral egg granules observed in
      all the other neoophoran Platyhelminthes. These vesicles can be considered an
      autapomorphic feature of the taxon Troglocaridicola; (b) The presence of
      proteinaceous acorn-shaped granules which remain scattered in the ooplasm
      throughout oogenesis and can be interpreted as residual yolk. This situation is
      shared with some Proseriata and Tricladida; (c) The precence of accessory cell
      processes between growing and mature oocytes, as is typical of some Proseriata
      and Tricladida. In the vitellarium, the presence of polyphenolic shell globules
      whose substructure does not correspond either to the multigranular pattern
      prevailing in representatives of Eulecithophora (Prolecithophora+Rhabdocoela) or
      to the homogeneous pattern found in Lecithoepitheliata. They have a
      meandering/concentric pattern of the content similar to that described in some
      Proseriata and Tricladida. On the basis of the ultrastructural characteristics of
      the female gonad described above, the position of Troglocaridicola in the taxon
      Rhabdocoela is discussed.

PMID- 11976030
TI  - Antennal sensilla of the ground beetle Bembidion properans Steph. (Coleoptera,
      Carabidae).
AB  - The arrangement of antennal sensilla was studied in female and male ground
      beetles Bembidion properans Steph. (Coleoptera, Carabidae) using scanning
      electron microscopy. The filiform antennae, 1.8-1.9 mm in length, consist of the
      scape, pedicel and nine flagellomeres. In both sexes, three types of sensilla
      chaetica, two types of sensilla trichodea, six types of sensilla basiconica, one
      type of sensilla coeloconica and one type of sensilla campaniformia were
      distinguished. The possible function of the sensilla is discussed and three types
      of sensilla are considered olfactory, sensilla trichodea type 2 and sensilla
      basiconica types 1 and 2. Olfactory sensilla form dorsal and/or ventral sensillar
      fields on the flagellomeres and occur sparsely or not at all outside these areas.
      No sexual differences in the types, number and distribution of antennal sensilla
      were found.

PMID- 11976031
TI  - Behavior of metal nanoparticles in the electron beam.
AB  - Fabrication and structural observation of In, Pd and Mo nanoparticles deposited
      on Si(110) substrates were performed in an ultrahigh vacuum field emission
      transmission electron microscope. In situ and/or dynamic observation of In
      nanoparticles showed fluctuation of their structures. The smaller particles of
      size of 3-5 nm showed frequent fluctuation, while the nanoparticles of more than
      10 nm in size showed relatively slower fluctuation. The bigger nanoparticles
      showed coalescence with a weaker beam. Pd nanoparticles of size of 3-5 nm showed
      structural fluctuation after 10-30 s of electron beam irradiation. Stronger beam
      irradiation resulted in the dissipation of the nanoparticles probably due to
      diffusion. Mo nanoparticles of size of 3-5 nm never showed structural
      fluctuation. Intensive electron beam irradiation resulted in the dissipation of
      the particles. The difference in structural fluctuation depending on the metal
      and the beam intensity, and the peculiar coalescence of In nanoparticles are
      discussed qualitatively.

PMID- 11976032
TI  - Morphometry of E-PTA stained synapses at the periphery of pathological lesions.
AB  - We carried out a novel application of the disector sampling and counting method,
      in a biopsy material from the pathologic human brain, to estimate the synaptic
      structural dynamics, quantitatively. Parietal cortex biopsies of adult (mean age:
      40.0 years) and old (mean age: 66.2 years) patients having undergone surgical
      intervention were investigated. The tissue samples were excised at the periphery
      of meningioma masses. Synaptic contact zones were stained en bloc by the ethanol
      phosphotungstic acid (E-PTA) preferential technique which selectively enhances
      both the pre- and post-synaptic paramembranous material separated by a sharp
      cleft against a very faint background, thus facilitating and objectifying
      synaptic morphometry. The disector method, associated with currently used
      morphometric formulas, enabled us to measure the number of synapses/m3 of tissue
      (numeric density: Nv); the total area of the synaptic contact zones/m3 of tissue
      (surface density: Sv) and the average synaptic size (S). In old vs. adult
      patients, Nv decreased by 7.5% (Mean (SEM): Adult 2.0040(0.0452); Old
      1.6780(0.0623)), while S increased by 17.5% (Adult 0.0203(0.0026); Old
      0.0246(0.0035)). Sv did not show any age-related difference. The same negative
      correlation between Nv and S has also been reported in physiological aging, and
      this suggests the active presence of age-related synaptic restructuring
      mechanisms in the nervous tissue surrounding a tumoral mass.

PMID- 11976033
TI  - FMRFamide-like midgut endocrine cells during the metamorphosis in Melipona
      quadrifasciata anthidioides (Hymenoptera, Apidae).
AB  - The FMRFamide, gastrin and cholecystokinin (CCK) occurrence in endocrine cells of
      insects has been described by several authors, although their functions are still
      not well defined for this group of animals. In the present study, the occurrence
      of endocrine cells producing FMRFamide, gastrin 1 and CCK-8 in the midgut
      (ventriculus) of Melipona quadrifasciata anthidioides (Hymenoptera, Apidae),
      before, during and after the metamorphosis, were investigated by means of pre
      embedding immunofluorescence techniques. FMRFamide reactivity was found in the
      endocrine cells as well as in the nervous fibers and neurons of the intestine of
      these bees. 'Open' and 'closed' types of FMRFamide-like cells were observed in
      last instar larvae. In the black eyed pupae the producing cells of FMRFamide
      seemed to be immature, and, in the workers, where the FMRFamide producing cells
      were more abundant, the production of this substance seemed to occur only in the
      open cells. Reactivity of the nervous fibers and neurons were observed, during
      the prepupae, white eyed pupae, and pink eyed pupae. The same did not occur with
      the midgut endocrine cells. There were no immunoreactivity observations for
      gastrin 1 and for CCK-8. The FMRFamide-like cells were present in the midgut of
      these insects during or close to the period that they were eating, which
      indicates that the FMRFamide may be involved in the control of the digestive
      process.

PMID- 11976034
TI  - Routine preparation of air-dried negatively stained and unstained specimens on
      holey carbon support films: a review of applications.
AB  - Several representative examples are given of the successful application of
      negative staining across the holes of holey carbon support films using 5% (w/v)
      ammonium molybdate solution containing trehalose. The inclusion of 0.1% (w/v)
      trehalose is considered to be most satisfactory, although good data have also
      been obtained in the presence of 0.01 and 1.0% (w/v) trehalose. The examples
      given fall into the following groups: protein molecules in the absence of
      polyethylene glycol (PEG), protein molecules in the presence of PEG (Mr 1000),
      lipoproteins, lipids and membranes, filaments and tubules, viruses in the absence
      of PEG, viruses in the presence of PEG, aqueous polymer solutions, and finally
      for comparison purposes, four unstained samples studied in the presence of
      trehalose alone. In all these cases, and many others not documented here,
      successful spreading of the sample across holes has been achieved, with the
      sample embedded within a thin film of air-dried ammonium molybdate+trehalose.
      These specimens can be rapidly produced and provide an alternative to negatively
      stained specimens on carbon support films. Specimen stability in the electron
      bean is good and such specimens can usually generate superior negatively stained
      TEM images without flattening and adsorption artefacts. The formation of 2-D
      arrays/crystals of protein molecules and viruses, suspended across holes in the
      presence of ammonium molbybdate+trehalose, and trehalose alone, is also
      demonstrated.

PMID- 11976035
TI  - pH-dependent effect of heat-induced antigen retrieval of epoxy section for
      electron microscopy.
AB  - The aim was to examine how the pH in the antigen retrieval medium (citrate)
      affects the yield of immunogold labeling of epoxy sections. Renal swine tissue
      with glomerular immune complex deposits with reactivity against IgG was embedded
      in epoxy resin. Prior to immunogold labeling with anti-IgG, ultrathin sections
      from these blocks were exposed to antigen retrieval by heating in citrate
      solution (pH 6, 9 or 12) at 95 degrees C in a PCR-machine or at 121 or 135
      degrees C min in an autoclave. The level of immunogold labeling was significantly
      higher for pH 12 than for pH 6 when heated at 95 degrees C (50% more intense),
      but at the cost of the ultrastructural preservation of the tissue. At pH 12 and
      temperature 135 degrees C the epoxy sections were completely destroyed. The
      sections which had been heated at 135 degrees C, pH 6 appeared significantly
      better both with respect to intensity of immunogold labeling (85% more intense)
      and to ultrastructural preservation than those which were heated at 95 degrees C,
      pH 12. Therefore, our results indicate that relatively low pH (pH 6) and high
      temperature is the method of choice, but low temperature and high pH can be used
      when an autoclave is not available.

PMID- 11976036
TI  - Electron tomography and computer visualisation of a three-dimensional 'photonic'
      crystal in a butterfly wing-scale.
AB  - A combination of transmission electron tomography and computer modelling has been
      used to determine the three-dimensional structure of the photonic crystals found
      in the wing-scales of the Kaiser-I-Hind butterfly (Teinopalpus imperialis). These
      scales presented challenges for electron microscopy because the periodicity of
      the structure was comparable to the thickness of a section and because of the
      complex connectivity of the object. The structure obtained has been confirmed by
      taking slices of the three-dimensional computer model constructed from the
      tomography and comparing these with transmission electron microscope (TEM) images
      of microtomed sections of the actual scale. The crystal was found to have chiral
      tetrahedral repeating units packed in a triclinic lattice.

PMID- 11976037
TI  - Preparation of metallized GaN/sapphire cross sections for TEM analysis using
      wedge polishing.
AB  - The tripod polisher has been used successfully in the past, in the preparation of
      difficult Si-based TEM cross-section specimens. Good TEM specimens, with large
      electron transparent areas, can be prepared in a relatively short time. In
      addition, wedge polishing considerably reduces the ion milling time because of
      the thinness of the final specimen. For metallized GaN on sapphire substrates,
      there are problems not inherent to Si-based materials: (1) sapphire is a
      difficult material to thin due to its high hardness and its mechanical
      instability when thinned below 20 m; (2) delamination of metal layers from the
      GaN can occur during polishing and/or ion milling; (3) markedly different ion
      milling rates for the metals and semiconductors. In this paper, wedge polishing
      has been modified to make it suitable for preparation of metallized GaN/sapphire
      samples or other metallized semiconductors and ceramics for TEM analysis. Using
      this method, TEM cross section specimens can be prepared with reasonably large
      thin areas.

PMID- 11976038
TI  - Improved low energy electron projection in-line holograms reconstruction:
      application to the holograms of a tungsten tip.
AB  - A modification of the classical calculation algorithm is presented which allows
      to minimize the effect of the long range oscillations created by the twin object
      in the reconstruction process of in-line holograms obtained by low energy
      electron projection microscopy. The reconstructed shapes of a tungsten tip,
      observed with different magnifications are shown.

PMID- 11976039
TI  - A simple, quick and reliable method for TEM cross-section preparation of ceramic
      oxide films on thin metal substrates.
AB  - We present a preparation method of cross-sectional thin foils for transmission
      electron microscopy (TEM). Samples are 0.1-1 m thick ceramic oxide films (CeO2,
      CeO2-YBa2Cu3O7 and CeO2-ZrO2/YO2-YBa2Cu3O7) epitaxially grown on 30-100 m highly
      textured nickel substrates. This method includes gluing the sample between a
      copper oxide dummy and a silicon dummy, followed by mechanical polishing and
      conventional ion milling. TEM cross-sectional samples obtained with this
      selection of dummies are electron-transparent up to a few tens of m parallel to
      the film surface. Several layer structures were analyzed by TEM and the results
      are shown. The preparation technique described here can be applied to any type of
      oxide film deposited on thin metal substrates.

PMID- 11976040
TI  - Electron microscopic determination of silver incorporation in collagen fibers as
      a model of organic-metal chiral supramolecular structure with optical anisotropic
      properties.
AB  - The high positive linear dichroism (LD) exhibited by silver-impregnated collagen
      fibers are thought to be caused by an ordered binding of silver nanoparticles to
      the collagen fibers. A correlation between LD, established by image analysis, and
      the size of silver particles as measured by electron microscopy was investigated
      in the same sections of silver-impregnated tendon collagen fibers. Silver
      particles were found to be periodically ordered along the collagen fibers, with
      some preference for the 67 nm collagen period and collagen a bands. The silver
      particle diameter for a sample of n=279 was 18.51 nm on average, with 95% of the
      values ranging between 17.90 and 19.14 nm. The finding that interference colors
      are correlated to abnormal dispersion of birefringence characteristics supports
      the concept that collagen fibers induce an ordered binding of silver distributed
      along the fibers.

PMID- 11976042
TI  - Technical aspects and utility of fMRI using BOLD and ASL.
AB  - Functional magnetic resonance imaging (fMRI) is an emerging methodology which
      provides various approaches to visualizing regional brain activity non
      invasively. Although the exact mechanisms underlying the coupling between neural
      function and fMRI signal changes remain unclear, fMRI studies have been
      successful in confirming task-specific activation in a variety of brain regions,
      providing converging evidence for functional localization. In particular, fMRI
      methods based on blood oxygenation level dependent (BOLD) contrast and arterial
      spin labeling (ASL) perfusion contrast have enabled imaging of changes in blood
      oxygenation and cerebral blood flow (CBF). While BOLD contrast has been widely
      used as the surrogate marker for neural activation and can provide reliable
      information on the neuroanatomy underlying transient sensorimotor and cognitive
      functions, recent evidence suggests perfusion contrast is suitable for studying
      relatively long term effects on CBF both at rest or during activation. New
      developments in combining or simultaneously measuring the electrophysiological
      and fMRI signals allow a new class of studies that capitalize on dynamic imaging
      with high spatiotemporal resolution. This article reviews the biophysical bases
      and methodologies of fMRI and its applications to the clinical neurosciences,
      with emphasis on the spatiotemporal resolution of fMRI and its coupling with
      neurophysiology under both normal and pathophysiological conditions.

PMID- 11976043
TI  - Effects of acute stimulation through contacts placed on the motor cortex for
      chronic stimulation.
AB  - OBJECTIVES: We tried to determine which neural elements were activated in awake
      subjects by stimulation through contacts placed chronically on the motor cortex.
      METHODS: We recorded the motor effects of stimulation through 4 disc contacts
      placed in the subdural space over the motor cortex in 9 patients undergoing
      chronic stimulation for the control of pain or for the control of the rigidity of
      multiple system atrophy. RESULTS: Single stimuli could elicit short latency motor
      evoked potentials or facilitate active motoneurons in the contralateral limbs.
      The responsible neural elements had a short chronaxie (the pulse duration
      necessary to reach threshold with a stimulus intensity twice that required to
      reach threshold at the longest pulse duration used) and refractory period
      implying that they were myelinated axons. The facilitation was larger with
      cathodal than with anodal monopolar stimulation. The short latency facilitation
      in response to the second of two stimuli was greater at condition test intervals
      of 2-5 ms. This enhancement could be demonstrated with conditioning stimuli
      subthreshold for the excitation of active motoneurons suggesting that it arose,
      in part, at the level of the cortex. Single cortical stimuli could result in
      inhibition of voluntarily activated motoneurons. The inhibition was larger with
      cathodal than anodal monopolar stimulation. The responsible neural elements also
      had a short chronaxie and refractory period. CONCLUSIONS: Stimulation in awake
      subjects through contacts placed chronically over the motor cortex appears to
      activate axons in the cortex, which excite both corticospinal neurons and
      inhibitory neurons.

PMID- 11976044
TI  - Task-specific modulation of anticipatory postural adjustments in individuals with
      hemiparesis.
AB  - OBJECTIVES: To study adaptation of anticipatory postural adjustments (APAs) in
      paretic and non-paretic muscles of individuals with hemiparesis to changes in the
      direction of the self-initiated perturbation and additional manual support.
      METHODS: Electrical activity of leg and trunk muscles on both sides of the body
      and ground reaction forces were recorded in 10 patients with hemiparesis and a
      group of matched control subjects. Subjects released a standard load, held in the
      hand of the extended relatively unimpaired arm. The load was released either in
      front of the body or to the side, with or without the impaired arm touching an
      external stable surface. RESULTS: APAs were reduced in individuals with
      hemiparesis, especially on the paretic side. In paretic muscles, the modulation
      of APAs with the direction of the perturbation was decreased or showed atypical
      patterns. Also the effects of touch were decreased in patients. Center of
      pressure displacements shortly after load release were similar in control
      subjects and patients. CONCLUSIONS: The results suggest that the ability of
      individuals with hemiparesis to prepare for a self-initiated predictable
      perturbation is reduced and that they may use alternative strategies of postural
      stabilization.

PMID- 11976045
TI  - Contribution of GABAergic cortical circuitry in shaping somatosensory evoked
      scalp responses: specific changes after single-dose administration of tiagabine.
AB  - OBJECTIVES: To determine whether conventional as well as high-frequency
      somatosensory evoked potentials (SEPs) to upper limb stimulation are influenced
      by GABAergic intracortical circuitry. METHODS: We recorded SEPs from 6 healthy
      volunteers before and after a single-oral administration of tiagabine.
      Conventional low-frequency SEPs have been obtained after stimulation of the
      median nerve, as well as after stimulation of the first phalanx of the thumb,
      which selectively involves cutaneous finger inputs. Median nerve SEPs have been
      further analyzed after digital narrow-bandpass filtering, to selectively examine
      high-frequency responses. Lastly, in order to explain scalp SEP distribution
      before and after tiagabine administration, we performed the brain electrical
      source analysis (BESA) of raw data. RESULTS: After tiagabine administration,
      conventional scalp SEPs showed a significant amplitude increase of parietal P24,
      frontal N24 and central P22 components. Similarly, BESA showed a significant
      strength increase of the second peak of activation of the first two perirolandic
      dipoles, which are likely to correspond to the N24/P24 and P22 generators. By
      contrast, no significant changes of high-frequency SEPs were induced by drug
      intake. CONCLUSIONS: Our findings support the view that both N24/P24 and P22 SEP
      components are probably generated by deep spiny cell hyperpolarization, which is
      strongly increased by inhibitory inputs from GABAergic interneurons. By
      considering the clear influence of inhibitory circuitry in shaping these SEP
      components, conventional scalp SEP recording could be useful in the functional
      assessment of the somatosensory cortex in different physiological and
      pathological conditions. By contrast, intrinsic firing properties of the cell
      population generating high-frequency SEP responses are unaffected by the increase
      of recurrent GABAergic inhibition.

PMID- 11976047
TI  - Effects of aging and sex on middle-latency somatosensory evoked potentials:
      normative data.
AB  - OBJECTIVES: To investigate the exact relationship of middle-latency somatosensory
      evoked potential (SEP) components (in particular the third negative component
      N60) to age and sex in a normal population. Middle-latency SEPs are believed to
      show a considerable inter-individual variability and there is little published
      information on normative data of these components. METHODS: Eighty-three healthy
      subjects aged 13-80 years were investigated using a standard SEP procedure.
      RESULTS: Both latency and amplitude of N60 increased substantially with age.
      Least square polynomial regression analysis showed that a quadratic curve best
      described its relationship (r2=0.67 for the latency, r2=0.18 for the amplitude).
      Data did not differ significantly with reference to sex or side of stimulation.
      CONCLUSIONS: The use of polynomial regression analysis for the determination of
      the normal range of N60 latencies and amplitudes has to be highly recommended. It
      might improve the accuracy with which abnormal results are detected in studies
      investigating the value of middle-latency SEPs in various diseases.

PMID- 11976046
TI  - Neural mechanisms for generation of tactile interference effects on somatosensory
      evoked magnetic fields in humans.
AB  - OBJECTIVES: We examined modification of somatosensory evoked fields following
      electric middle finger stimulation with interference to the same and surrounding
      digits in 13 subjects. METHODS: During electric middle finger stimulation,
      concurrent tactile stimulation was applied to the middle finger, to the index and
      ring fingers, and to the thumb and the little finger, individually. RESULTS: The
      amplitudes of the N20m and the P30m were significantly reduced by the
      interference to the middle finger, and to the index and ring fingers. The former
      interference induced more prominent attenuation than the latter. The amplitudes
      of the P60m did not show significant changes by any kind of the interference.
      CONCLUSIONS: The N20m and the P30m were attenuated according to the cortical
      distance between electrically and mechanically activated 3b areas. Pyramidal
      neurons are interconnected by intrinsic horizontal collaterals, even if their
      representations are segregated. The activation of the intrinsic collaterals
      induces direct excitation and indirect inhibition (via inhibitory interneurons)
      to the target pyramidal neurons. The result indicates that the activation of the
      intrinsic collaterals inhibits, on balance, the postsynaptic pyramidal targets,
      thereby generating the attenuation of the N20m and P30m.

PMID- 11976048
TI  - Lower number of K-complexes and K-alphas in sleep bruxism: a controlled
      quantitative study.
AB  - OBJECTIVES: Although patients with sleep bruxism (SB) show a higher incidence of
      rhythmic masticatory muscle activity (RMMA) during sleep than matched normal
      controls, they are good sleepers. Sleep macrostructure (e.g. total sleep time,
      sleep latency, number of awakenings or sleep stage shifts and sleep stage
      duration) is similar between groups. Differences in sleep microstructure between
      SB patients and normals have been investigated only in few studies. The aim of
      the present study was to quantify number of microarousals, K-complexes, K-alphas,
      EEG spindles, and the density of slow wave activity, in both groups, in order to
      better understand the pathophysiology of SB. METHODS: Ten normal sleepers were
      matched for age and gender with 10 patients who exhibited frequent tooth-grinding
      during sleep. Using quantitative polysomnographic measures, we compared the above
      mentioned sleep variables in both groups. Data are presented as indices for total
      sleep and for consecutive non-rapid eye movement (non-REM) episodes over non-REM
      to rapid eye movement (REM) cycles and per hour of sleep. RESULTS: SB patients
      showed 6 times more RMMA episodes per hour of sleep than normals (P<0.001), with
      a higher frequency in the second and third non-REM to REM cycles. SB patients
      presented 42.7% fewer K-complexes per hour of stage 2 sleep, but only normals
      showed a decline from the first to fourth non-REM episode. Only 24% of SB-RMMA
      episodes were associated with K-complexes in 60 s. The number of K-alphas was 61%
      lower in SB patients, no change across non-REM episodes was noted. While no
      difference in electroencephalographic (EEG) spindles or slow wave activity (SWA)
      was observed between groups, EEG spindles increased and SWA decreased linearly
      over consecutive non-REM to REM cycles. CONCLUSIONS: According to our
      observations, good sleep in SB patients is characterized by a low incidence of K
      complexes or K-alphas and by the absence of any difference in other sleep
      microstructure variables or SWA.

PMID- 11976049
TI  - Electroencephalogram processing using neural networks.
AB  - The electroencephalogram (EEG), a highly complex signal, is one of the most
      common sources of information used to study brain function and neurological
      disorders. More than 100 current neural network applications dedicated to EEG
      processing are presented. Works are categorized according to their objective
      (sleep analysis, monitoring anesthesia depth, brain-computer interface, EEG
      artifact detection, EEG source-based localization, etc.). Each application
      involves a specific approach (long-term analysis or short-term EEG segment
      analysis, real-time or time delayed processing, single or multiple EEG-channel
      analysis, etc.), for which neural networks were generally successful. The
      promising performances observed are demonstrative of the efficiency and efficacy
      of systems developed. This review can aid researchers, clinicians and
      implementors to understand up-to-date interest in neural network tools for EEG
      processing. The extended bibliography provides a database to assist in possible
      new concepts and idea development.

PMID- 11976050
TI  - A standardized boundary element method volume conductor model.
AB  - OBJECTIVES: We used a 3-compartment boundary element method (BEM) model from an
      averaged magnetic resonance image (MRI) data set (Montreal Neurological
      Institute) in order to provide simple access to realistically shaped volume
      conductor models for source reconstruction, as compared to individually derived
      models. The electrode positions were transformed into the model's coordinate
      system, and the best fit dipole results were transformed back to the original
      coordinate system. The localization accuracy of the new approach was tested in a
      comparison with simulated data and with individual BEM models of epileptic spike
      data from several patients. METHODS: The standard BEM model consisted of a total
      of 4770 nodes, which describe the smoothed cortical envelope, the outside of the
      skull, and the outside of the skin. The electrode positions were transformed to
      the model coordinate system by using 3-5 fiducials (nasion, left and right
      preauricular points, vertex, and inion). The transformation consisted of an
      averaged scaling factor and a rigid transformation (translation and rotation).
      The potential values at the transformed electrode positions were calculated by
      linear interpolation from the stored transfer matrix of the outer BEM compartment
      triangle net. After source reconstruction the best fit dipole results were
      transformed back into the original coordinate system by applying the inverse of
      the first transformation matrix. RESULTS: Test-dipoles at random locations and
      with random orientations inside of a highly refined reference BEM model were used
      to simulate noise-free data. Source reconstruction results using a spherical and
      the standardized BEM volume conductor model were compared to the known dipole
      positions. Spherical head models resulted in mislocation errors at the base of
      the brain. The standardized BEM model was applied to averaged and unaveraged
      epileptic spike data from 7 patients. Source reconstruction results were compared
      to those achieved by 3 spherical shell models and individual BEM models derived
      from the individual MRI data sets. Similar errors to that evident with
      simulations were noted with spherical head models. Standardized and
      individualized BEM models were comparable. CONCLUSIONS: This new approach to head
      modeling performed significantly better than a simple spherical shell
      approximation, especially in basal brain areas, including the temporal lobe. By
      using a standardized head for the BEM setup, it offered an easier and faster
      access to realistically shaped volume conductor models as compared to deriving
      specific models from individual 3-dimensional MRI data.

PMID- 11976051
TI  - Systematic source estimation of spikes by a combination of independent component
      analysis and RAP-MUSIC. I: Principles and simulation study.
AB  - OBJECTIVES: We propose a combination of independent component analysis (ICA) and
      recursively applied and projected multiple signal classification (RAP-MUSIC) as a
      new approach to dipole source estimation of epileptiform discharges. The method
      is minimally dependent on subjective decisions. METHODS: Ten
      electroencephalographic (EEG) data matrices were generated by computer, each
      matrix including real background activity from a normal subject and an array of
      added simulated spikes. Each spike was a summation of two transients originating
      from slightly different 'original dipole sources'. The unaveraged EEG matrices
      were decomposed by ICA, and source estimation was performed by applying RAP-MUSIC
      to the spatial information defined by the ICA components showing epileptiform
      activity in their waveform. For comparison, dipoles were also estimated from the
      same matrices using two existing methods: RAP-MUSIC based on eigen-decomposition
      of the covariance matrices of averaged spikes and common spatial pattern
      decomposition. RESULTS: In every simulated EEG data matrix, two dipoles close to
      the original sources were estimated by the present method. Their unaveraged
      activities were also similar to those of the original sources. The two existing
      methods gave less precise results than the proposed method. CONCLUSIONS: RAP
      MUSIC based on ICA thus proved promising for source estimation of unaveraged
      epileptiform discharges.

PMID- 11976052
TI  - Systematic source estimation of spikes by a combination of independent component
      analysis and RAP-MUSIC. II: Preliminary clinical application.
AB  - OBJECTIVES: We tried to estimate epileptic sources by a combination of
      independent component analysis (ICA) and recursively applied and projected
      multiple signal classification (RAP-MUSIC) in real epileptiform EEG discharges.
      METHODS: EEG data including an array of spikes from 3 patients were decomposed by
      ICA, and source estimation was performed by applying RAP-MUSIC to the spatial
      information defined by the set of ICA components that showed epileptiform
      activity in their waveform. Sources were also estimated from the same data using
      RAP-MUSIC based on eigen-decomposition of the covariance matrix of averaged
      spikes, and common spatial pattern decomposition for comparison. RESULTS: RAP
      MUSIC based on ICA could estimate generally correct epileptic sources in the 3
      patients, and its results were better than those of the other methods, when
      compared to intracerebral data. The present analysis proceeded without
      introduction of subjective decision after data selection. The separation of
      epileptiform discharges from the background is essential for this analysis, and
      was successfully performed in the real EEG data. CONCLUSIONS: RAP-MUSIC based on
      ICA appears promising for estimation of epileptic sources with minimal dependence
      on subjective decisions in the process of analysis. In particular, it was not
      necessary to select the number of sources.

PMID- 11976053
TI  - Detection and description of non-linear interdependence in normal multichannel
      human EEG data.
AB  - OBJECTIVES: This study examines human scalp electroencephalographic (EEG) data
      for evidence of non-linear interdependence between posterior channels. The
      spectral and phase properties of those epochs of EEG exhibiting non-linear
      interdependence are studied. METHODS: Scalp EEG data was collected from 40
      healthy subjects. A technique for the detection of non-linear interdependence was
      applied to 2.048 s segments of posterior bipolar electrode data. Amplitude
      adjusted phase-randomized surrogate data was used to statistically determine
      which EEG epochs exhibited non-linear interdependence. RESULTS: Statistically
      significant evidence of non-linear interactions were evident in 2.9% (eyes open)
      to 4.8% (eyes closed) of the epochs. In the eyes-open recordings, these epochs
      exhibited a peak in the spectral and cross-spectral density functions at about 10
      Hz. Two types of EEG epochs are evident in the eyes-closed recordings; one type
      exhibits a peak in the spectral density and cross-spectrum at 8 Hz. The other
      type has increased spectral and cross-spectral power across faster frequencies.
      Epochs identified as exhibiting non-linear interdependence display a tendency
      towards phase interdependencies across and between a broad range of frequencies.
      CONCLUSIONS: Non-linear interdependence is detectable in a small number of
      multichannel EEG epochs, and makes a contribution to the alpha rhythm. Non-linear
      interdependence produces spatially distributed activity that exhibits phase
      synchronization between oscillations present at different frequencies. The
      possible physiological significance of these findings are discussed with
      reference to the dynamical properties of neural systems and the role of
      synchronous activity in the neocortex.

PMID- 11976054
TI  - On the time resolution of event-related desynchronization: a simulation study.
AB  - OBJECTIVES: To investigate the time resolution of different methods for the
      computation of event-related desynchronization/synchronization (ERD/ERS),
      including one based on Hilbert transform. METHODS: In order to better understand
      the time resolution of ERD/ERS, which is a function of factors such as the exact
      computation method, the frequency under study, the number of trials, and the
      sampling frequency, we simulated sudden changes in oscillation amplitude as well
      as very short and closely spaced events. RESULTS: Hilbert-based ERD yields very
      similar results to ERD integrated over predefined time intervals (block ERD), if
      the block length is half the period length of the studied frequency. ERD predicts
      the onset of a change in oscillation amplitude with an error margin of only 10-30
      ms. On the other hand, the time the ERD response needs to climb to its full
      height after a sudden change in oscillation amplitude is quite long, i.e. between
      200 and 500 ms. With respect to sensitivity to short oscillatory events, the
      ratio between sampling frequency and electroencephalographic frequency band plays
      a major role. CONCLUSIONS: (1) The optimal time interval for the computation of
      block ERD is half a period of the frequency under investigation. (2) Due to the
      slow impulse response, amplitude effects in the ERD may in reality be caused by
      duration differences. (3) Although ERD based on the Hilbert transform does not
      yield any significant advantages over classical ERD in terms of time resolution,
      it has some important practical advantages.

PMID- 11976055
TI  - Regulatory differences between Ca(2+)-ATPase in plasma membranes from chicken
      (nucleated) and pig (anucleated) erythrocytes.
AB  - Kinetic and regulatory properties of the plasma membrane Ca(2+)-ATPase activity
      from chicken (nucleated) erythrocytes were studied and compared to those from pig
      (anucleated) erythrocytes. In the absence of known activators: (1) Ca(2+)
      affinity for the Ca(2+)-ATPase activity from nucleated erythrocytes was 12-fold
      higher than that from pig erythrocytes, and thus the enzyme is sensitive to
      physiological Ca(2+) concentrations; (2) the enzyme from chicken erythrocytes
      showed two apparent Km values for ATP, as compared to one apparent Km value
      displayed by pig erythrocytes; (3) Ca(2+)-ATPase inserted in chicken erythrocyte
      membranes showed a low sensitivity to activation by phosphatidylinositol-4
      phosphate; (4) when p-NPP was used as substrate, the activity of chicken
      erythrocytes was high, similar to that attained by pig erythrocytes, but barely
      sensitive to activation by dimethylsulfoxide and calmodulin. ATP hydrolysis was
      10-fold lower than that displayed by pig erythrocytes and the maximal velocity
      was activated three-fold by calmodulin. The enzyme was insensitive to alkaline
      phosphatase treatment and showed a single phosphorylation band in
      electrophoresis, ruling out the possibility of previous modulation by endogenous
      kinases and/or by partial proteolysis. The differences may be attributed to some
      endogenous modulator, to distinct isoforms, or to a difference in the E(1)/E(2)
      states of the enzyme.

PMID- 11976056
TI  - The effects of naltrexone, an opioid receptor antagonist, on plasma LH levels in
      common carp (Cyprinus carpio L.).
AB  - Naltrexone-an opioid receptor antagonist, was administered intraperitoneally to
      sexually mature male and female common carp in the prespawning period, in order
      to investigate its effects on spontaneous or sGnRH-A-stimulated LH secretion.
      Naltrexone and sGnRH-A were injected at the same time. The possible involvement
      of a dopaminergic system in this process was studied in males pre-treated with
      pimozide (a dopamine receptor antagonist) 12 h before naltrexone and/or sGnRH-A
      administration. Blood samples for the analysis of carp LH concentrations were
      taken just before the injections and then after the injections, serial sampling
      during 24 h was performed. In male carp, naltrexone (500 or 5000 microg kg(-1))
      decreased spontaneous LH release, but there were no effects of naltrexone on
      sGnRH-A-stimulated LH secretion. In males pre-treated with pimozide, a similar
      response to naltrexone injection (500 microg kg(-1)) as in pirnozide non-treated
      fish, was observed. The highest dose of naltrexone, 5000 microg kg(-1),
      significantly stimulated LH release, in response to sGnRH-A administration in
      pimozide pre-treated males. In female carp, contrary to males, naltrexone at a
      dose of 500 microg kg(-1), caused significant stimulation of spontaneous LH
      release. These data indicate that endogenous opioid peptides modify LH secretion
      in sexually mature carp. In males, they stimulate LH secretion, acting rather on
      the hypothalamic GnRH system and in females, opioids inhibit LH release by the
      influence on the dopaminergic system.

PMID- 11976058
TI  - Dopamine D1 receptors in the gills of Chinese crab Eriocheir sinensis.
AB  - Our investigations indicate the existence of binding sites for [3H]SCH23390 on
      crude membrane preparations in the anterior and posterior gills of the Chinese
      crab, Eriocheir sinensis acclimated to freshwater (FW) or seawater (SW). Maximum
      specific binding in the posterior gills is always higher than in the anterior
      gills, independent of saline acclimation. Kd values are similar in the two
      regions, suggesting the same affinity of both types of gills for the ligand,
      either from FW or from SW crabs.

PMID- 11976057
TI  - Purification and characterization of metallothionein-like cadmium binding protein
      from Asian periwinkle Littorina brevicula.
AB  - Although mussels and oysters in the ocean are known to act as bioconcentrators
      for contaminants such as heavy metals, their ability to survive in heavily
      polluted water is relatively limited. The Asian periwinkle, Littorina brevicula,
      is one species that can accumulate a variety of environmental heavy metals, and
      the expression of its metal binding protein (MBP) is induced by cadmium. To
      better characterize this protein and its detoxification mechanism against
      cadmium, the present work examined the induction of a cadmium binding protein (Cd
      BP) in Littorina brevicula exposed to 400 microg/l CdCl(2) for 30 days. The
      induced Cd-BP was purified by chromatography from the supernatants of homogenized
      organs (digestive gland, gonad, gill and kidney). This Cd-BP was found to consist
      of 103 amino acids, was rich in Cys (21 residues), and partial C-terminal
      sequence obtained by MALDI-TOF MS analysis revealed a Cys-XXX-Cys motif, which
      resembles a typical feature of mollusc metallothionein (MT). The Cd-BP molecular
      weight of 9.8 kDa is a little larger than that of other MTs.

PMID- 11976059
TI  - Tetracycline-Cu(II) photo-induced fragmentation of serum albumin.
AB  - The protein-damaging potential of photosensitized tetracycline hydrochloride
      alone and in combination with the metal ion Cu(II) was assessed using serum
      albumin as a model protein. Exposure of tetracycline to white light in an aqueous
      solution triggered the generation of significant amounts of reactive oxygen
      species (ROS) and engendered substantial protein damage. The appearance of
      distinct low-molecular-mass protein bands on 10% SDS-polyacrylamide gel
      ascertained the tetracycline concentration-dependent fragmentation of albumin.
      Photoexcited tetracycline in combination with 100 microM Cu(II) enhanced the
      protein fragmentation process with concurrent increase in free radical
      production. The significant release of acid-soluble amino groups and carbonyl
      groups from treated albumin provided quantitative estimation of protein
      fragmentation at 0-1.0 mM concentrations of tetracycline. Cu(II) ions per se did
      not cause any perceptible protein damage. The results with free radical quenchers
      suggested the role of hydroxyl radicals (*OH) in tetracycline-Cu(II)-induced
      protein fragmentation, as no superoxide dismutase (SOD)-mediated quenching effect
      was noted. The generation of free radicals upon tetracycline photoexcitation and
      consequent protein fragmentation may be considered as important factors in
      augmentation of tetracycline-induced phototoxic responses.

PMID- 11976060
TI  - Effect of hydrogen peroxide on antioxidant enzymes and metallothionein level in
      the digestive gland of Mytilus galloprovincialis. cavalett@unipmn.it.
AB  - The pro-oxidant effect of H2O2 at a concentration of 20 microM was examined in
      the digestive gland of Mytilus galloprovincialis, a bivalve mollusc frequently
      used in biomonitoring programs. The oxidative stress caused by H2O2 has been
      evaluated in terms of lipid peroxidation and lysosomal system alteration. Complex
      cellular antioxidant defence mechanisms of the mussel were investigated at the
      enzymatic and non-enzymatic level in order to explain their relative role in
      reducing the risk of oxidative injury. Metallothionein, glutathione, superoxide
      dismutase, catalase and glutathione peroxidase were assayed after 1, 4 and 7 days
      of exposure to H2O2. The metallothionein content showed an increase by 43% after
      4 days of exposure, followed by a decrease back to control values at 7 days.
      Antioxidant enzyme activities followed a similar pattern with a moderate increase
      after 1 or 4 days of treatment and a return to control values at 7 days. All data
      indicate a 'transient' oxidative stress response, after which mussel cells
      restore the redox balance.

PMID- 11976061
TI  - Delayed gametogenesis of Mya arenaria in the Saguenay fjord (Canada): a
      consequence of endocrine disruptors?
AB  - The Saguenay fjord located in Canada on the north coast of the Saint-Lawrence
      Estuary, is well known for its multiple contaminations following a linear
      distribution upstream to downstream. Mya arenaria is well established in the
      fjord and potentially exposed to persistent sediment contamination as an
      endobenthic bivalve. From May to October 1997, clams energy storage and
      utilization in the gonad was shown to be closely linked with reproduction.
      Wherever the sampling site location in the fjord, a seasonal pattern is evident
      for lipid and glycogen levels in the gonad, this, reflecting the vitellogenic
      process. Nevertheless, in comparison with energy status and gametogenesis of
      clams collected on the north coast of the Saint-Lawrence Estuary, clams located
      in the fjord have to face limited nutritive conditions resulting in a single and
      shorter reproductive period. Although environmental factors could explain
      differences in physiological condition and reproductive status observed between
      clams from the fjord and the estuary, our results can discriminate clams from the
      upper part of the fjord, according to a delayed gametogenesis, concomitant with
      significant higher gonad glycogen concentrations observed in June 1996 and 1997.
      A persistent dysfunction of a vitellogenic process is suspected to be due to the
      exposure to anti-estrogenic contaminants.

PMID- 11976062
TI  - Insecticide susceptibility and detoxication enzyme activities among Coptotermes
      formosanus Shiraki workers sampled from different locations in New Orleans.
AB  - Coptotermes formosanus Shiraki worker termites were sampled from 20 locations in
      the City Park area of New Orleans, LA. The termites were subsequently assayed to
      determine their susceptibility to cypermethrin, chlordane and chlorpyrifos, and
      detoxication enzyme activity. Cypermethrin was most toxic against Formosan
      subterranean termite workers, chlorpyrifos exhibited intermediate toxicity and
      chlordane was least toxic. A comparison of insecticide susceptibility between the
      most and least tolerant colonies revealed 1.9-, 1.7- and 1.8-fold differences in
      susceptibility for cypermethrin, chlorpyrifos and chlordane, respectively. As
      with the bioassay data, although significant differences were noted, a great deal
      of overlap was observed among the colonies for total cytochrome P450 content
      (difference of 2.2-fold between high and low value) aldrin epoxidation (3.6-fold)
      and cytosolic esterase (3.9-fold) activity. No significant differences were
      observed among the colonies for methoxyresorufin O-demethylase or glutathione S
      transferase activity. Conversely, microsomal esterase activity varied greatly; a
      38-fold difference was observed between the most (Cf1776) and least (Cf1387)
      active colonies. However, no significant correlation was observed between
      insecticide susceptibility and microsomal esterase activity. In fact, no
      significant correlations were observed between any of the enzyme activities
      measured and insecticide susceptibility. These results are discussed in the
      context of insecticide selection and future control effectiveness.

PMID- 11976063
TI  - Purification and characterisation of glutathione S-transferases from the
      freshwater clam Corbicula fluminea (Muller).
AB  - Glutathione S-transferases (GSTs) are involved in the phase II detoxification
      metabolism. To provide a molecular basis for their use as biomarkers of
      pollution, cytosolic GSTs from the freshwater clam Corbicula fluminea have been
      purified by glutathione-Sepharose affinity chromatography, anion-exchange
      chromatography (AEC) and reversed-phase (RP) HPLC. SDS-PAGE of visceral mass (VM)
      affinity-purified extracts revealed four subunits with apparent molecular masses
      (MW) of 30.2, 29.2, 28.5 and 27.2 kDa. Analysis by non-denaturing PAGE revealed
      three acidic dimeric proteins with apparent MW of 64, 55 and 45 kDa, named GSTc1,
      GSTc2 and GSTc3, respectively, based on their elution order by AEC. Only GSTc2
      and GSTc3 exhibited GST activity towards 1-chloro-2,4-dinitrobenzene. A tissue
      specific subunit pattern was obtained by RP-HPLC of affinity-purified extracts
      from VM and gills (GI): three major peaks were resolved, one of which was common
      to both tissues. MW of each VM subunit was determined by electrospray ionisation
      mass spectrometry: 23602+/-1 Da for the major subunit and 23289+/-1 Da for the
      minor ones. Immunoblot analysis revealed all subunits from both tissues were
      related to the Pi-class GSTs. In addition, minor VM subunits were slightly
      related to the Mu-class ones. The interest of such molecular studies in
      biomonitoring programs is discussed.

PMID- 11976064
TI  - Involvement of reactive oxygen stress in cadmium-induced cellular damage in
      Euglena gracilis.
AB  - Inorganic cadmium (Cd) causes cellular damage to eukaryotes and to tissues of
      higher organisms, including DNA strand breaks and intracellular membrane damage,
      as a result of reactive oxygen stress. We previously reported cadmium chloride
      (CdCl2)-induced abnormal cell morphologies in the unicellular eukaryote Euglena
      gracilis Z (a plant cell model) and its achlorophyllous mutant SMZ strain (an
      animal cell model). The present study was undertaken to examine whether exposure
      of both strains to CdCl2 would lead to similar cellular responses, especially
      with regard to reactive oxygen stress loading and cellular damage. The results
      indicate that CdCl2 exposure can induce morphological alteration, linked to
      reactive oxygen stress. Both E. gracilis Z and SMZ cells subjected to short-term,
      high-dose CdCl2 exposure showed long 'comet lengths' in the so-called 'Comet'
      assay, indicating DNA strand breaks. Similarly, short-term, high-dose CdCl(2)
      exposed cells and CdCl(2)-induced morphologically altered cells showed intense
      fluorescence of dihydrofluorescein (HFLUOR) after incubation with
      dihydrofluorescein diacetate (HFLUOR-DA). Positive data on the generation and
      involvement of intracellular reactive oxygen species (ROS) were obtained from
      long-term, low-dose CdCl(2)-exposed E. gracilis Z and SMZ, by thiobarbituric acid
      (TBA)-malondialdehyde (MDA) complex analyses.

PMID- 11976065
TI  - Species-specific responses of constitutively active receptor (CAR)-CYP2B
      coupling: lack of CYP2B inducer-responsive nuclear translocation of CAR in marine
      teleost, scup (Stenotomus chrysops).
AB  - The mammalian constitutively active receptor (CAR) is a novel ligand-activated
      transcription factor that participates in controlling the expression of
      cytochrome P450 2B (CYP2B) genes in response to pharmaceutical agents
      (phenobarbital) and halogenated aromatic hydrocarbons (ortho-substituted PCBs).
      The occurrence and physiological function of this protein are as yet unknown in
      marine animals, where there has been a paradoxical lack of induction by PB-type
      chemicals. One approach to understanding CAR function is to study the
      evolutionary history of processes such as CAR-CYP2B coupling. In this study, CAR
      function was evaluated in a representative teleost fish (scup, Stenotomus
      chrysops). Treatment of scup with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene
      (TCPOBOP), which is one of the most potent CYP2B inducers in mouse, caused no
      increase in hepatic alkoxyresorufin O-dealkylase activity nor in immunodetectable
      CYP2B-like protein levels. Western blot analyses of scup livers using anti-human
      CAR antisera revealed the occurrence of a putative CAR homologue in nuclear and
      cytoplasmic fractions, but no nuclear accumulation of CAR following TCPOBOP
      treatment, which is a first step regulating the transcriptional activation of
      CYP2B genes in mouse. Immunohistochemical study also showed no translocation of
      CAR into nucleus in the hepatocytes of TCPOBOP-treated scup. These results
      suggest that there may be species-specific differences in CAR activation or CAR
      CYP2B coupling signaling transduction in fish from those in mouse.

PMID- 11976066
TI  - Ca2+-activated K+ channel blockers induce PKC modulated oscillatory contractions
      in guinea pig trachea.
AB  - Mechanisms underlying the Ca2+-activated K+ channel (K(Ca)) blockers-induced
      oscillatory contractions were investigated in guinea pig tracheal smooth muscle.
      The mean oscillatory frequencies induced by charybdotoxin (ChTX; 100 nM) and
      iberiotoxin (IbTX; 100 nM) were 9.8+/-0.8 (counts/h) and 8.0+/-1.3 (counts/h),
      respectively. Apamin (1 microM ), a blocker of SK(Ca), induced no contraction in
      guinea pig trachea and did not affect ChTX-induced oscillatory contractions. In
      Ca2+ free solution, no ChTX-induced contraction was observed. Nifedipine (100
      nM), a blocker of voltage-dependent Ca2+ channels, and SK&F 96365 (10 microM), a
      blocker of capacitative Ca2+ entry, completely abolished ChTX-induced oscillatory
      contractions. Ryanodine (1 microM) decreased the amplitude, but increased the
      frequency of the oscillatory contractions. Thapsigargin (1 microM) changed
      contractions from the oscillatory type to the sustained type. Moreover, the
      protein kinase C (PKC) inhibitor, bisindolylamaleimide I (1 microM), decreased
      the amplitude and frequency, but PKC activator, phorbol 12-myristate 13-acetate
      (1 microM), increased the frequency of oscillatory contractions. These results
      suggest that K(Ca) inhibitors-induced oscillatory contractions are initiated by
      Ca2+ influx through L-type voltage-dependent Ca2+ channels. The ryanodine
      sensitive calcium release channels in the sarcoplasmic reticulum may play an
      important role in maintaining the oscillatory contractions. Moreover, PKC
      activity modulates these oscillatory contractions.

PMID- 11976068
TI  - Vitellogenin induction by 17beta-estradiol and 17alpha-ethinylestradiol in male
      zebrafish (Danio rerio).
AB  - Adult male zebrafish (Danio rerio) were exposed to 17beta-estradiol (E2) or
      17alpha-ethinylestradiol (EE2) in flow-through systems for 8 days. This was done
      to compare the sensitivity of the estrogen inducible vitellogenin (Vtg) biomarker
      system of this proposed OECD test guideline species to other relevant test
      species. Vtg was quantified in whole body homogenate by a species-specific ELISA.
      Actual water concentrations of E2 and EE2 were quantified by LC-MS, with
      detection limits of 1.0 and 0.6 ng/l, respectively. Vtg induction (LOEC) occurred
      in whole body homogenate at actual water concentrations of 21 ng E2/l and 3.0 ng
      EE2/l, respectively. As an alternative to the ANOVA approach, the relationship
      between the percentage of responding fish (Vtg) and the external E2 or EE2
      concentration was determined by logistic regression analysis. Based on the
      regression analysis, EC-values could be determined: EC10, EC50 and EC90 were
      15.4, 41.2 and 67.1 ng E2/l, respectively and 0.92, 2.51 and 4.09 ng EE2/l,
      respectively. Comparisons of these response limits to corresponding values for
      rainbow trout (Oncorhynchus mykiss), fathead minnow (Pimephales promelas) and
      Japanese medaka (Oryzias latipes) revealed the zebrafish as a sensitive test
      species.

PMID- 11976067
TI  - Attenuating effects of melatonin on pilocarpine-induced seizures in rats.
AB  - Daily melatonin (10-50 mg/kg, i.p.) treatment at 08.30 h or 17.00 h for 1 week of
      female rats (2-months-old) increased the latency to the appearance of the first
      convulsion in the pilocarpine-induced seizure model. Other behavior parameters
      remained unaltered. The anticonvulsant effect of melatonin seemed to be more
      intense at the light-dark transition. Moreover, the effect of repeated melatonin
      treatment was also age-related, since it showed a lower threshold in 2-month-old
      than in 21-day-old rats, and the acute treatment was not efficient. [3H]N
      methylscopolamine binding was unaltered in the hippocampus and striatum of adult
      rats after the association of melatonin and pilocarpine. While muscarinic binding
      was unaltered in adult rats, it increased in the hippocampus of young rats in the
      presence of melatonin (50 mg/kg) and pilocarpine, and did not change in the
      striatum. Melatonin partially recovered [3H]GABA binding in the hippocampus in
      the presence of pilocarpine-induced seizures, and intensified pilocarpine effects
      in the striatum of adult rats.

PMID- 11976070
TI  - Lipid-lowering--translating evidence into benefits.

PMID- 11976071
TI  - A new reality: achieving cholesterol-lowering goals in clinical practice.
AB  - Physicians often fail to achieve recommended low-density lipoprotein (LDL)
      cholesterol goals for their patients using lipid-lowering therapies in the
      primary care setting. A variety of factors may contribute to this failure,
      including inadequate effectiveness of lipid-lowering drugs in reducing LDL
      cholesterol at commonly used doses. In the Lipid Assessment Treatment Project (L
      TAP), for example, the success rates for lipid-regulating therapies and
      treatments according to National Cholesterol Education Program (NCEP) Adult
      Treatment Panel II (ATP II) LDL cholesterol goals were 43% for bile acid
      sequestrants, 39% for niacin, 32% for gemfibrozil, 28% for psyllium fiber, 40%
      for statins, and 40% for combination therapy. Rosuvastatin is a new statin that
      has been shown to achieve significantly greater reductions in LDL cholesterol
      compared with pravastatin, simvastatin, and atorvastatin in primary
      hypercholesterolemia and enabled greater proportions of patients to achieve LDL
      cholesterol goals. Similarly, rosuvastatin proved superior to atorvastatin in
      lowering LDL cholesterol in patients with familial hypercholesterolemia, with
      more patients achieving LDL cholesterol goals. Data from these trials suggest
      that rosuvastatin is as safe and well tolerated as other statins. The
      availability of lipid-lowering drugs with greater LDL cholesterol-lowering
      effects could simplify the approach to coronary heart disease risk reduction in
      primary care.

PMID- 11976072
TI  - Evidence-based goals versus achievement in clinical practice in secondary
      prevention of coronary heart disease: findings in EUROASPIRE II.
AB  - Recommendations for reducing risk of recurrence in patients with established
      coronary heart disease (CHD) or other atherosclerotic disease were published by
      the Joint European Societies in 1994 and 1998. The first EUROASPIRE survey of
      clinical practice of secondary CHD prevention, performed in 1995 and 1996, found
      that 19% of CHD patients smoked cigarettes, 25% had body mass index (BMI) > or
      =30 kg/m(2), 53% had blood pressure > or =140/90 mmHg, and 44% had plasma total
      cholesterol > or =5.5 mmol/l. EUROASPIRE II, conducted in 1999 and 2000, found
      that 21% of patients smoked cigarettes, 31% had BMI > or =30 kg/m(2), 50% had
      blood pressure > or =140/90 mmHg, and 58% had serum total cholesterol > or =5.0
      mmol/l. It is clear that there are still considerable opportunities in Europe to
      reduce risk of recurrent CHD through lifestyle changes, rigorous control of other
      risk factors, and more effective use of proven drug therapies.

PMID- 11976073
TI  - The lower the better? Reviewing the evidence for more aggressive cholesterol
      reduction and goal attainment.
AB  - There is considerable evidence that more aggressive lowering of low-density
      lipoprotein (LDL) cholesterol is associated with increased benefits in reducing
      atherosclerotic disease burden, supporting the notion of 'the lower, the better.'
      However, achievement of currently recommended goals has proven difficult with
      lipid-lowering agents at the commonly used doses. Current options for achieving
      greater LDL cholesterol reductions include use of high doses of the most
      effective of the available statins and use of high or moderate statin doses in
      combination with agents that work in a complementary manner (e.g. bile acid
      sequestrants or niacin). Near-term options may include statins with increased LDL
      cholesterol-lowering effectiveness and better-tolerated secondary agents that can
      be combined with statin therapy. Rosuvastatin (Crestor, AstraZeneca) is a new
      statin that may prove to be of considerable utility in achieving greater LDL
      cholesterol reductions than are currently possible with existing statins. Recent
      phase III clinical trials have shown that this agent produces significantly
      greater LDL cholesterol reductions than atorvastatin, simvastatin, or pravastatin
      in patients with primary hypercholesterolemia and significantly greater
      reductions than the maximal dose of atorvastatin in patients with familial
      hypercholesterolemia.

PMID- 11976074
TI  - High risk/high priority: familial hypercholesterolemia--a paradigm for molecular
      medicine.
AB  - Familial hypercholesterolemia provides an excellent model for demonstrating how
      disease prevention can be facilitated by molecular characterization of a genetic
      disease. To achieve the most efficient yield in terms of patient identification
      and coronary heart disease prevention, family information should be obtained in
      the primary care setting. In the majority of cases, measurement of cholesterol
      levels in a patient's relatives is sufficient to determine presence or absence of
      familial hypercholesterolemia, and DNA testing may be used in those cases in
      which cholesterol level is not diagnostic. DNA testing has enabled a more refined
      assessment of the absolute cardiovascular risks associated with familial
      hypercholesterolemia, which is currently estimated to have a 50% mortality rate
      by age 60. Recent investigations using DNA testing have suggested that familial
      hypercholesterolemia is implicated in one of 12 cases of cardiovascular disease
      in individuals aged <65 years. Only the most potent lipid-modifying therapies
      should be used in those found to be affected by this disorder. In this regard, it
      is noteworthy that the new statin rosuvastatin (Crestor; AstraZeneca) was
      recently shown to produce significantly greater low-density lipoprotein (LDL)
      cholesterol reductions and high-density lipoprotein (HDL) cholesterol increases
      than atorvastatin in a large study in patients with familial
      hypercholesterolemia, while bringing more of these patients to LDL cholesterol
      goals. Familial hypercholesterolemia should serve as a paradigm of molecular
      medicine: we understand the genetic defect, we have the tools to identify the
      individuals who are at high risk of disease because they have the defect, and we
      have therapies that can prevent clinical disease. It nevertheless requires effort
      on the part of clinicians to ensure that optimal risk assessment is performed and
      optimal treatment provided.

PMID- 11976075
TI  - Optimizing the pharmacology of statins: characteristics of rosuvastatin.
AB  - Rosuvastatin (Crestor, AstraZeneca) is a new synthetic statin that exhibits a
      number of highly desirable pharmacologic characteristics. The drug has a high
      affinity for the active site of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase and exhibits greater potency in inhibiting enzyme activity and
      cholesterol synthesis in vitro than other statins. The effects of rosuvastatin
      are selective for hepatic cells, and there is minimal uptake of the drug by
      nonhepatic tissues. The vast majority of biologic activity of the drug is
      associated with the parent compound, which does not appear to undergo extensive
      metabolism. Hepatic metabolism appears to be minimal, and there is little
      evidence of metabolic interaction with cytochrome P450 3A4. In an early-phase
      study, rosuvastatin produced large and dose-related decreases in low-density
      lipoprotein (LDL) cholesterol of up to 65% in hypercholesterolemic patients.
      Rosuvastatin should constitute an important addition to current lipid-lowering
      interventions.

PMID- 11976076
TI  - Auxotrophic yeast strains in fundamental and applied research.

PMID- 11976077
TI  - Production of fumonisin analogs by Fusarium species.

PMID- 11976078
TI  - Denaturation of either Manduca sexta aminopeptidase N or Bacillus thuringiensis
      Cry1A toxins exposes binding epitopes hidden under nondenaturing conditions.
AB  - The effect of polypeptide denaturation of Bacillus thuringiensis Cry1A toxins or
      purified Manduca sexta 120-kDa aminopeptidase N on the specificities of their
      interactions was investigated. Ligand and dot blotting experiments were conducted
      with (125)I-labeled Cry1Ac, Cry1Ac mutant (509)QNR-AAA(511) (QNR-AAA), or 120-kDa
      aminopeptidase N as the probe. Mutant QNR-AAA does not bind the N
      acetylgalactosamine moiety on the 120-kDa aminopeptidase. Both (125)I-Cry1Ac and
      (125)I-QNR-AAA bound to 210- and 120-kDa proteins from M. sexta brush border
      membrane vesicles and purified 120-kDa aminopeptidase N on ligand blots. However,
      on dot blots (125)I-QNR-AAA bound brush border vesicles but did not bind purified
      aminopeptidase except when aminopeptidase was denatured. In the reciprocal
      experiment, (125)I-aminopeptidase bound Cry1Ac but did not bind QNR-AAA. (125)I
      aminopeptidase bound Cry1Ab to a limited extent but not the Cry1Ab domain I
      mutant Y153D or Cry1Ca. However, denatured (125)I-aminopeptidase detected each
      Cry1A toxin and mutant but not Cry1Ca on dot blots. The same pattern of
      recognition occurred with native (nondenatured) (125)I-aminopeptidase probe and
      denatured toxins as the targets. The broader pattern of toxin-binding protein
      interaction is probably due to peptide sequences being exposed upon denaturation.
      Putative Cry toxin-binding proteins identified by the ligand blot technique need
      to be investigated under native conditions early in the process of identifying
      binding proteins that may serve as functional toxin receptors.

PMID- 11976079
TI  - Effect of polyclonal, monoclonal, and recombinant (single-chain variable
      fragment) antibodies on in vitro morphology, growth, and metabolism of the
      phytopathogenic mollicute Spiroplasma citri.
AB  - Antibodies are known to affect the morphology, growth, and metabolism of
      mollicutes and thus may serve as candidate molecules for a plantibody-based
      control strategy for plant-pathogenic spiroplasmas and phytoplasmas. Recombinant
      single-chain variable fragment (scFv) antibodies are easy to engineer and express
      in plants, but their inhibitory effects on mollicutes have never been evaluated
      and compared with those of polyclonal and monoclonal antibodies. We describe the
      morphology, growth, and glucose metabolism of Spiroplasma citri in the presence
      of polyclonal, monoclonal, and recombinant antibodies directed against the
      immunodominant membrane protein spiralin. We showed that the scFv antibodies had
      no effect on S. citri glucose metabolism but were as efficient as polyclonal
      antibodies in inhibiting S. citri growth in liquid medium. Inhibition of motility
      was also observed.

PMID- 11976080
TI  - Simultaneous transport of two bacterial strains in intact cores from Oyster,
      Virginia: biological effects and numerical modeling.
AB  - The transport characteristics of two adhesion-deficient, indigenous groundwater
      strains, Comamonas sp. strain DA001 and Erwinia herbicola OYS2-A, were studied by
      using intact sediment cores (7 by 50 cm) from Oyster, Va. Both strains are gram
      negative rods (1.10 by 0.56 and 1.56 by 0.46 microm, respectively) with strongly
      hydrophilic membranes and a slightly negative surface charge. The two strains
      exhibited markedly different behaviors when they were transported through
      granular porous sediment. To eliminate any effects of physical and chemical
      heterogeneity on bacterial transport and thus isolate the biological effect, the
      two strains were simultaneously injected into the same core. DA001 cells were
      metabolically labeled with (35)S and tagged with a vital fluorescent stain, while
      OYS2-A cells were metabolically labeled with (14)C. The fast decay of (35)S
      allowed deconvolution of the two isotopes (and therefore the two strains).
      Dramatic differences in the transport behaviors were observed. The breakthrough
      of DA001 and the breakthrough of OYS2-A both occurred before the breakthrough of
      a conservative tracer (termed differential advection), with effluent recoveries
      of 55 and 30%, respectively. The retained bacterial concentration of OYS2-A in
      the sediment was twofold higher than that of DA001. Among the cell properties
      analyzed, the statistically significant differences between the two strains were
      cell length and diameter. The shorter, larger-diameter DA001 cells displayed a
      higher effluent recovery than the longer, smaller-diameter OYS2-A cells. CXTFIT
      modeling results indicated that compared to the DA001 cells, the OYS2-A cells
      experienced lower pore velocity, higher porosity, a higher attachment rate, and a
      lower detachment rate. All these factors may contribute to the observed
      differences in transport.

PMID- 11976081
TI  - Identification of a salt-induced primary transporter for glycine betaine in the
      methanogen Methanosarcina mazei Go1.
AB  - The salt adaptation of the methanogenic archaeon Methanosarcina mazei Go1 was
      studied at the physiological and molecular levels. The freshwater organism M.
      mazei Go1 was able to adapt to salt concentrations up to 1 M, and the addition of
      the compatible solute glycine betaine to the growth medium facilitated adaptation
      to higher salt concentrations. Transport studies with cell suspensions revealed a
      salt-induced glycine betaine uptake activity in M. mazei Go1, and inhibitor
      studies argue for a primary transport device. Analysis of the genome of M. mazei
      Go1 identified a homolog of known primary glycine betaine transporters. This gene
      cluster was designated Ota (osmoprotectant transporter A). Its sequence and gene
      organization are very similar to those of the glycine betaine transporter OpuA of
      Bacillus subtilis. Northern blot analysis of otaC revealed a salt-dependent
      transcription of this gene. Ota is the first identified salt-induced transporter
      for compatible solutes in Archaea.

PMID- 11976082
TI  - Taxis response of various denitrifying bacteria to nitrate and nitrite.
AB  - The taxis response of Rhodobacter sphaeroides 2.4.1 and 2.4.3, Rhodopseudomonas
      palustris, and Agrobacterium tumefaciens to nitrate and nitrite was evaluated by
      observing the macroscopic behavior of cells suspended in soft agar and incubated
      under various conditions. R. sphaeroides 2.4.3, which is capable of both nitrate
      and nitrite reduction, showed a taxis response to both nitrate and nitrite. R.
      sphaeroides 2.4.1, which contains nitrate reductase but not nitrite reductase,
      did not show a taxis response towards either nitrogen oxide. Insertional
      inactivation of the nitrite reductase structural gene or its transcriptional
      regulator, NnrR, in strain 2.4.3 caused a loss of a taxis response towards both
      nitrate and nitrite. An isolate of 2.4.1 carrying a copy of the nitrite reductase
      gene from 2.4.3 showed a taxis response to both nitrogen oxides. The taxis
      response of 2.4.3 was observed under anaerobic conditions, suggesting that the
      taxis response was due to nitrate and nitrite respiration, not to inhibition of
      oxygen respiration by respiration of nitrogen oxides. Strain 2.4.3 showed a taxis
      response to nitrate and nitrite under photosynthetic and aerobic conditions.
      Changing the carbon source in the culture medium caused an unexpected subtle
      shift in the taxis response of 2.4.3 to nitrite. A taxis response to nitrogen
      oxides was also observed in R. palustris and A. tumefaciens. R. palustris
      exhibited a taxis response to nitrite but not to nitrate, while A. tumefaciens
      exhibited a response to both compounds.

PMID- 11976083
TI  - Tri13 and Tri7 determine deoxynivalenol- and nivalenol-producing chemotypes of
      Gibberella zeae.
AB  - Gibberella zeae, a major cause of cereal scab, can be divided into two chemotypes
      based on production of the 8-ketotrichothecenes deoxynivalenol (DON) and
      nivalenol (NIV). We cloned and sequenced a Tri13 homolog from each chemotype. The
      Tri13 from a NIV chemotype strain (88-1) is located in the trichothecene gene
      cluster and carries an open reading frame similar to that of Fusarium
      sporotrichioides, whereas the Tri13 from a DON chemotype strain (H-11) carries
      several mutations. To confirm the roles of the Tri13 and Tri7 genes in
      trichothecene production by G. zeae, we genetically altered toxin production in
      88-1 and H-11. In transgenic strains, the targeted deletion of Tri13 from the
      genome of 88-1 caused production of DON rather than NIV. Heterologous expression
      of the 88-1 Tri13 gene alone or in combination with the 88-1 Tri7 gene conferred
      on H-11 the ability to synthesize NIV; in the latter case, 4-acetylnivalenol (4
      ANIV) also was produced. These results suggest that Tri13 and Tri7 are required
      for oxygenation and acetylation of the oxygen at C-4 during synthesis of NIV and
      4-ANIV in G. zeae. These functional analyses of the Tri13 and Tri7 genes provide
      the first clear evidence for the genetic basis of the DON and NIV chemotypes in
      G. zeae.

PMID- 11976085
TI  - Novel plant-microbe rhizosphere interaction involving Streptomyces lydicus
      WYEC108 and the pea plant (Pisum sativum).
AB  - A previously undescribed plant-microbe interaction between a root-colonizing
      Streptomyces species, S. lydicus WYEC108, and the legume Pisum sativum is
      described. The interaction is potentially of great importance to the health and
      growth in nature of this nodulating legume. The root-colonizing soil actinomycete
      S. lydicus WYEC108 influences pea root nodulation by increasing root nodulation
      frequency, possibly at the level of infection by Rhizobium spp. S. lydicus also
      colonizes and then sporulates within the surface cell layers of the nodules.
      Colonization leads to an increase in the average size of the nodules that form
      and improves the vigor of bacteroids within the nodules by enhancing nodular
      assimilation of iron and possibly other soil nutrients. Bacteroid accumulation of
      the carbon storage polymer, poly-beta-hydroxybutyrate, is reduced in colonized
      nodules. Root nodules of peas taken from agricultural fields in the Palouse hills
      of northern Idaho were also found to be colonized by actinomycete hyphae. We
      hypothesize that root and nodule colonization is one of several mechanisms by
      which Streptomyces acts as a naturally occurring plant growth-promoting bacterium
      in pea and possibly other leguminous plants.

PMID- 11976084
TI  - Impaired cutinase secretion in Saccharomyces cerevisiae induces irregular
      endoplasmic reticulum (ER) membrane proliferation, oxidative stress, and ER
      associated degradation.
AB  - Impaired secretion of the hydrophobic CY028 cutinase invokes an unfolded protein
      response (UPR) in Saccharomyces cerevisiae cells. Here we show that the UPR in
      CY028-expressing S. cerevisiae cells is manifested as an aberrant morphology of
      the endoplasmic reticulum (ER) and as extensive membrane proliferation compared
      to the ER morphology and membrane proliferation of wild-type CY000-producing S.
      cerevisiae cells. In addition, we observed oxidative stress, which resulted in a
      21-fold increase in carbonylated proteins in the CY028-producing S. cerevisiae
      cells. Moreover, CY028-producing S. cerevisiae cells use proteasomal degradation
      to reduce the amount of accumulated CY028 cutinase, thereby attenuating the
      stress invoked by CY028 cutinase expression. This proteasomal degradation occurs
      within minutes and is characteristic of ER-associated degradation (ERAD). Our
      results clearly show that impaired secretion of the heterologous, hydrophobic
      CY028 cutinase in S. cerevisiae cells leads to protein aggregation in the ER,
      aberrant ER morphology and proliferation, and oxidative stress, as well as a UPR
      and ERAD.

PMID- 11976086
TI  - Assessment of the genetic diversity among arcobacters isolated from poultry
      products by using two PCR-based typing methods.
AB  - In this study, enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and
      randomly amplified polymorphic DNA PCR (RAPD-PCR) were optimized for
      characterization of Arcobacter butzleri, Arcobacter cryaerophilus, and Arcobacter
      skirrowii. In addition, a simple and rapid DNA extraction method was tested for
      use in both typing procedures. Both methods had satisfactory typeability and
      discriminatory power, but the fingerprints generated with ERIC-PCR were more
      reproducible and complex than those obtained with RAPD-PCR. The use of nondiluted
      boiled cell suspensions as DNA templates was found to be very useful in ERIC-PCR.
      Characterization of large numbers of Arcobacter isolates is therefore preferably
      performed by the ERIC-PCR procedure. Isolates for which almost identical ERIC
      fingerprints are generated may subsequently be characterized by RAPD-PCR,
      although adjustment and standardization of the amount of the DNA template are
      necessary. In the second part of this study, the genotypic diversity of
      arcobacters present on broiler carcasses was assessed by using both typing
      methods. A total of 228 cultures from 24 samples were examined after direct
      isolation and enrichment. The isolates were identified by using a multiplex PCR
      as A. butzleri (n = 182) and A. cryaerophilus (n = 46). A total of 131 types (91
      A. butzleri types and 40 A. cryaerophilus types) were discerned without
      discordance between the two typing techniques. The analysis of the poultry
      isolates showed that poultry products may harbor not only more than one species
      but also multiple genotypes. All genotypes were confined to one poultry sample,
      and only three genotypes were found after simultaneous enrichment and direct
      isolation. These results demonstrate that different outcomes can be obtained in
      epidemiological studies depending on the isolation procedure used and the number
      of isolates characterized.

PMID- 11976087
TI  - Genes from Pseudomonas sp. strain BS involved in the conversion of L-2-amino
      Delta(2)-thiazolin-4-carbonic acid to L-cysteine.
AB  - DL-2-amino-Delta(2)-thiazolin-4-carbonic acid (DL-ATC) is a substrate for
      cysteine synthesis in some bacteria, and this bioconversion has been utilized for
      cysteine production in industry. We cloned a DNA fragment containing the genes
      involved in the conversion of L-ATC to L-cysteine from Pseudomonas sp. strain BS.
      The introduction of this DNA fragment into Escherichia coli cells enabled them to
      convert L-ATC to cysteine via N-carbamyl-L-cysteine (L-NCC) as an intermediate.
      The smallest recombinant plasmid, designated pTK10, contained a 2.6-kb insert DNA
      fragment that has L-cysteine synthetic activity. The nucleotide sequence of the
      insert DNA revealed that two open reading frames (ORFs) encoding proteins with
      molecular masses of 19.5 and 44.7 kDa were involved in the L-cysteine synthesis
      from DL-ATC. These ORFs were designated atcB and atcC, respectively, and their
      gene products were identified by overproduction of proteins encoded in each ORF
      and by the maxicell method. The functions of these gene products were examined
      using extracts of E. coli cells carrying deletion derivatives of pTK10. The
      results indicate that atcB and atcC are involved in the conversion of L-ATC to L
      NCC and the conversion of L-NCC to cysteine, respectively. atcB was first
      identified as a gene encoding an enzyme that catalyzes thiazolin ring opening.
      AtcC is highly homologous with L-N-carbamoylases. Since both enzymes can only
      catalyze the L-specific conversion from L-ATC to L-NCC or L-NCC to L-cysteine, it
      is thought that atcB and atcC encode L-ATC hydrolase and N-carbamyl-L-cysteine
      amidohydrolase, respectively.

PMID- 11976088
TI  - Microbial load of drinking water reservoir tributaries during extreme rainfall
      and runoff.
AB  - Hygienic and microbiological examinations of watercourses are usually not carried
      out during heavy rainfall and runoff events. After rainfall or snowmelt, there
      are often massive increases in turbidity in flooding creeks in mountain ranges,
      which are frequently interpreted as an indication of microbial contamination. The
      aim of this study was to quantify the microbial loads of watercourses during such
      runoff events and to compare these loads with loads occurring during regular
      conditions. In a 14-month monitoring period we investigated the microbial loads
      of three tributaries of different drinking water reservoirs. A total of 99 water
      samples were taken under different runoff conditions and analyzed to determine
      physical, chemical, bacterial, and parasitic parameters. Thirty-two water samples
      were considered event samples during nine measuring series. The criteria for
      events, based on duration and intensity of precipitation, water depth gauge
      measurements, and dynamics, had been fixed before the investigation for each
      creek individually. Of the physical and chemical parameters examined, only the
      turbidity, pH, and nitrate values differed clearly from the values obtained for
      regular samples. Most of the bacteriological parameters investigated (colony,
      Escherichia coli, coliform, fecal streptococcal, and Clostridium perfringens
      counts) increased considerably during extreme runoff events. If relevant sources
      of parasitic contamination occurred in catchment areas, the concentrations of
      Giardia and Cryptosporidium rose significantly during events. The results show
      that substantial shares of the total microbial loads in watercourses and in
      drinking water reservoirs result from rainfall and extreme runoff events.
      Consequently, regular samples are considered inadequate for representing the
      microbial contamination of watercourse systems. The procedures for raw water
      surveillance in the context of multiple-barrier protection and risk assessment
      ought to include sampling during extreme runoff situations.

PMID- 11976089
TI  - Isolation and characterization of endophytic colonizing bacteria from agronomic
      crops and prairie plants.
AB  - Endophytic bacteria reside within plant hosts without causing disease symptoms.
      In this study, 853 endophytic strains were isolated from aerial tissues of four
      agronomic crop species and 27 prairie plant species. We determined several
      phenotypic properties and found approximately equal numbers of gram-negative and
      gram-positive isolates. In a greenhouse study, 28 of 86 prairie plant endophytes
      were found to colonize their original hosts at 42 days postinoculation at levels
      of 3.5 to 7.7 log(10) CFU/g (fresh weight). More comprehensive colonization
      studies were conducted with 373 corn and sorghum endophytes. In growth room
      studies, none of the isolates displayed pathogenicity, and 69 of the strains were
      recovered from corn or sorghum seedlings at levels of 8.3 log(10) CFU/plant or
      higher. Host range greenhouse studies demonstrated that 26 of 29 endophytes were
      recoverable from at least one host other than corn and sorghum at levels of up to
      5.8 log(10) CFU/g (fresh weight). Long-range dent corn greenhouse studies and
      field trials with 17 wild-type strains and 14 antibiotic-resistant mutants
      demonstrated bacterial persistence at significant average colonization levels
      ranging between 3.4 and 6.1 log(10) CFU/g (fresh weight) up to 78 days
      postinoculation. Three prairie and three agronomic endophytes exhibiting the most
      promising levels of colonization and an ability to persist were identified as
      Cellulomonas, Clavibacter, Curtobacterium, and Microbacterium isolates by 16S
      rRNA gene sequence, fatty acid, and carbon source utilization analyses. This
      study defines for the first time the endophytic nature of Microbacterium
      testaceum. These microorganisms may be useful for biocontrol and other
      applications.

PMID- 11976090
TI  - Rapid PCR-based method which can determine both phenotype and genotype of
      Lactococcus lactis subspecies.
AB  - A highly efficient, rapid, and reliable PCR-based method for distinguishing
      Lactococcus lactis subspecies (L. lactis subsp. lactis and L. lactis subsp.
      cremoris) is described. Primers complementary to positions in the glutamate
      decarboxylase gene have been constructed. PCR analysis with extracted DNA or with
      cells of different L. lactis strains resulted in specific fragments. The length
      polymorphism of the PCR fragments allowed a clear distinction of the L. lactis
      subspecies. The amplified fragment length polymorphism with the primers and the
      restriction fragment length polymorphism of the amplified products agreed
      perfectly with the identification based on genotypic and phenotypic analyses,
      respectively. Isolates from cheese starters were investigated by this method, and
      amplified fragments of genetic variants were found to be approximately 40 bp
      shorter than the typical L. lactis subsp. cremoris fragments.

PMID- 11976091
TI  - Partitioning of bacterial communities between seawater and healthy, black band
      diseased, and dead coral surfaces.
AB  - Distinct partitioning has been observed in the composition and diversity of
      bacterial communities inhabiting the surface and overlying seawater of three
      coral species infected with black band disease (BBD) on the southern Caribbean
      island of Curacao, Netherlands Antilles. PCR amplification and sequencing of
      bacterial 16S rRNA genes (rDNA) with universally conserved primers have
      identified over 524 unique bacterial sequences affiliated with 12 bacterial
      divisions. The molecular sequences exhibited less than 5% similarity in bacterial
      community composition between seawater and the healthy, black band diseased, and
      dead coral surfaces. The BBD bacterial mat rapidly migrates across and kills the
      coral tissue. Clone libraries constructed from the BBD mat were comprised of
      eight bacterial divisions and 13% unknowns. Several sequences representing
      bacteria previously found in other marine and terrestrial organisms (including
      humans) were isolated from the infected coral surfaces, including Clostridium
      spp., Arcobacter spp., Campylobacter spp., Cytophaga fermentans, Cytophaga
      columnaris, and Trichodesmium tenue.

PMID- 11976092
TI  - Fusaric acid-producing strains of Fusarium oxysporum alter 2,4
      diacetylphloroglucinol biosynthetic gene expression in Pseudomonas fluorescens
      CHA0 in vitro and in the rhizosphere of wheat.
AB  - The phytotoxic pathogenicity factor fusaric acid (FA) represses the production of
      2,4-diacetylphloroglucinol (DAPG), a key factor in the antimicrobial activity of
      the biocontrol strain Pseudomonas fluorescens CHA0. FA production by 12 Fusarium
      oxysporum strains varied substantially. We measured the effect of FA production
      on expression of the phlACBDE biosynthetic operon of strain CHA0 in culture media
      and in the wheat rhizosphere by using a translational phlA'-'lacZ fusion. Only FA
      producing F. oxysporum strains could suppress DAPG production in strain CHA0, and
      the FA concentration was strongly correlated with the degree of phlA repression.
      The repressing effect of FA on phlA'-'lacZ expression was abolished in a mutant
      that lacked the DAPG pathway-specific repressor PhlF. One FA-producing strain
      (798) and one nonproducing strain (242) of F. oxysporum were tested for their
      influence on phlA expression in CHA0 in the rhizosphere of wheat in a gnotobiotic
      system containing a sand and clay mineral-based artificial soil. F. oxysporum
      strain 798 (FA(+)) repressed phlA expression in CHA0 significantly, whereas
      strain 242 (FA(-)) did not. In the phlF mutant CHA638, phlA expression was not
      altered by the presence of either F. oxysporum strain 242 or 798. phlA expression
      levels were seven to eight times higher in strain CHA638 than in the wild-type
      CHA0, indicating that PhlF limits phlA expression in the wheat rhizosphere.

PMID- 11976093
TI  - Characterization of Trichodesmium spp. by genetic techniques.
AB  - The genetic diversity of Trichodesmium spp. from natural populations (off Bermuda
      in the Sargasso Sea and off North Australia in the Arafura and Coral Seas) and of
      culture isolates from two regions (Sargasso Sea and Indian Ocean) was
      investigated. Three independent techniques were used, including a DNA
      fingerprinting method based on a highly iterated palindrome (HIP1), denaturing
      gradient gel electrophoresis of a hetR fragment, and sequencing of the internal
      transcribed spacer (ITS) of the 16S-23S rDNA region. Low genetic diversity was
      observed in natural populations of Trichodesmium spp. from the two hemispheres.
      Culture isolates of Trichodesmium thiebautii, Trichodesmium hildebrandtii,
      Trichodesmium tenue, and Katagnymene spiralis displayed remarkable similarity
      when these techniques were used, suggesting that K. spiralis is very closely
      related to the genus TRICHODESMIUM: The largest genetic variation was found
      between Trichodesmium erythraeum and all other species of Trichodesmium,
      including a species of KATAGNYMENE: Our data obtained with all three techniques
      suggest that there are two major clades of Trichodesmium spp. The HIP1
      fingerprinting and ITS sequence analyses allowed the closely related species to
      be distinguished. This is the first report of the presence of HIP1 in marine
      cyanobacteria.

PMID- 11976094
TI  - Linking central metabolism with increased pathway flux: L-valine accumulation by
      Corynebacterium glutamicum.
AB  - Mutants of Corynebacterium glutamicum were made and enzymatically characterized
      to clone ilvD and ilvE, which encode dihydroxy acid dehydratase and transaminase
      B, respectively. These genes of the branched-chain amino acid synthesis were
      overexpressed together with ilvBN (which encodes acetohydroxy acid synthase) and
      ilvC (which encodes isomeroreductase) in the wild type, which does not excrete L
      valine, to result in an accumulation of this amino acid to a concentration of 42
      mM. Since L-valine originates from two pyruvate molecules, this illustrates the
      comparatively easy accessibility of the central metabolite pyruvate. The same
      genes, ilvBNCD, overexpressed in an ilvA deletion mutant which is unable to
      synthesize L-isoleucine increased the concentration of this amino acid to 58 mM.
      A further dramatic increase was obtained when panBC was deleted, making the
      resulting mutant auxotrophic for D-pantothenate. When the resulting strain, C.
      glutamicum 13032DeltailvADeltapanBC with ilvBNCD overexpressed, was grown under
      limiting conditions it accumulated 91 mM L-valine. This is attributed to a
      reduced coenzyme A availability and therefore reduced flux of pyruvate via
      pyruvate dehydrogenase enabling its increased drain-off via the L-valine
      biosynthesis pathway.

PMID- 11976095
TI  - Role of acetate in production of an autoinducible class IIa bacteriocin in
      Carnobacterium piscicola A9b.
AB  - Carnobacterium piscicola strain A9b isolated from cold smoked salmon inhibits
      growth of the food-borne pathogen Listeria monocytogenes partly due to the
      production of a proteinaceous compound (L. Nilsson, L. Gram, and H. H. Huss. J.
      Food Prot. 62:336-342, 1999). The purpose of the present study was to purify the
      compound and describe factors affecting its production, with particular emphasis
      on food-relevant factors. Amino acid sequencing showed that the compound is a
      class IIa bacteriocin with an N-terminal amino acid sequence identical to that of
      carnobacteriocin B2. The production of the bacteriocin was autoinducible, and the
      threshold level for induction was 9.6 x 10(-10) M. We also report, for the first
      time, that acetate acts as an induction factor, with a threshold concentration of
      0.3 to 12 mM. Acetate could not act as an inducer during the late exponential
      phase of C. piscicola A9b. The induction of bacteriocin production showed a dose
      dependent relationship at acetate concentrations of up to 10 to 20 mM (depending
      on the growth medium) and at a concentration of 1.9 x 10(-8) M for the
      bacteriocin itself; a saturation level of bacteriocin specific activity was
      reached at these concentrations of induction factors. The combined use of both
      inducers did not enhance the saturation level of bacteriocin production compared
      to that seen with the use of each inducer alone. Increasing NaCl and glucose
      concentrations negatively influenced the efficiency of acetate as an induction
      factor. Based on the results, carnobacteriocin B2 was used as an induction factor
      to manipulate the production of bacteriocin in cold smoked salmon juice and thus
      improve the ability to inhibit L. monocytogenes.

PMID- 11976096
TI  - Response of endophytic bacterial communities in potato plants to infection with
      Erwinia carotovora subsp. atroseptica.
AB  - The term endophyte refers to interior colonization of plants by microorganisms
      that do not have pathogenic effects on their hosts, and various endophytes have
      been found to play important roles in plant vitality. In this study, cultivation
      independent terminal restriction fragment length polymorphism analysis of 16S
      ribosomal DNA directly amplified from plant tissue DNA was used in combination
      with molecular characterization of isolates to examine the influence of plant
      stress, achieved by infection with the blackleg pathogen Erwinia carotovora
      subsp. atroseptica, on the endophytic population in two different potato
      varieties. Community analysis clearly demonstrated increased bacterial diversity
      in infected plants compared to that in control plants. The results also indicated
      that the pathogen stress had a greater impact on the bacteria population than the
      plant genotype had. Partial sequencing of the 16S rRNA genes of isolated
      endophytes revealed a broad phylogenetic spectrum of bacteria, including members
      of the alpha, beta, and gamma subgroups of the Proteobacteria, high- and low-G+C
      content gram-positive organisms, and microbes belonging to the Flexibacter
      Cytophaga-Bacteroides group. Screening of the isolates for antagonistic activity
      against E. carotovora subsp. atroseptica revealed that 38% of the endophytes
      protected tissue culture plants from blackleg disease.

PMID- 11976097
TI  - Gastrointestinal tract location of Escherichia coli O157:H7 in ruminants.
AB  - Experimentally inoculated sheep and cattle were used as models of natural
      ruminant infection to investigate the pattern of Escherichia coli O157:H7
      shedding and gastrointestinal tract (GIT) location. Eighteen forage-fed cattle
      were orally inoculated with E. coli O157:H7, and fecal samples were cultured for
      the bacteria. Three distinct patterns of shedding were observed: 1 month, 1 week,
      and 2 months or more. Similar patterns were confirmed among 29 forage-fed sheep
      and four cannulated steers. To identify the GIT location of E. coli O157:H7,
      sheep were sacrificed at weekly intervals postinoculation and tissue and digesta
      cultures were taken from the rumen, abomasum, duodenum, lower ileum, cecum,
      ascending colon, descending colon, and rectum. E. coli O157:H7 was most prevalent
      in the lower GIT digesta, specifically the cecum, colon, and feces. The bacteria
      were only inconsistently cultured from tissue samples and only during the first
      week postinoculation. These results were supported in studies of four Angus
      steers with cannulae inserted into both the rumen and duodenum. After the steers
      were inoculated, ruminal, duodenal, and fecal samples were cultured periodically
      over the course of the infection. The predominant location of E. coli O157:H7
      persistence was the lower GIT. E. coli O157:H7 was rarely cultured from the rumen
      or duodenum after the first week postinoculation, and this did not predict if
      animals went on to shed the bacteria for 1 week or 1 month. These findings
      suggest the colon as the site for E. coli O157:H7 persistence and proliferation
      in mature ruminant animals.

PMID- 11976098
TI  - Transcript levels of the eukaryotic translation initiation factor 5A gene peak at
      early G(1) phase of the cell cycle in the dinoflagellate Crypthecodinium cohnii.
AB  - A cDNA encoding a eukaryotic translation initiation factor 5A (eIF-5A) homolog in
      heterotrophic dinoflagellate Crypthecodinium cohnii (CceIF-5A) was isolated
      through random sequencing of a cDNA library. The predicted amino acid sequence
      possesses the 12 strictly conserved amino acids around lysine 52 (equivalent to
      lysine 50 or 51 in other eukaryotes). A single 1.2-kb band was detected in
      Northern blot analysis. In synchronized C. cohnii cells, the transcript level
      peaked at early G(1) and decreased dramatically on the entry to S phase. Although
      this has not been previously reported, studies of budding yeast (Saccharomyces
      cerevisiae) and certain mammalian cell types suggest a role for eIF-5A in the
      G(1)/S transition of the eukaryotic cell cycle. Phylogenetic trees constructed
      with 26 other published eIF-5A sequences suggest that CceIF-5A, while falling
      within the eukaryotic branches, forms a lineage separate from those of the
      plants, animals, and archaebacteria. The posttranslational modification of eIF-5A
      by a transfer of a 4-aminobutyl moiety from spermidine to conserved lysine 50 or
      51, forming amino acid hypusine, is the only demonstrated specific function of
      polyamines in cell proliferation. It has been suggested that polyamines stimulate
      population growth of bloom-forming dinoflagellates in the sea. We demonstrate
      here putrescine-stimulated cell proliferation. Furthermore, ornithine
      decarboxylase inhibitor D-difluoromethylornithine and the specific hypusination
      inhibitor N-guanyl-1,7-diaminoheptane exhibited inhibitory effects in two species
      of dinoflagellates. The possible links of polyamines and saxitoxin synthesis to
      the arginine cycle are also discussed.

PMID- 11976099
TI  - Spatial distribution of total, ammonia-oxidizing, and denitrifying bacteria in
      biological wastewater treatment reactors for bioregenerative life support.
AB  - Bioregenerative life support systems may be necessary for long-term space
      missions due to the high cost of lifting supplies and equipment into orbit. In
      this study, we investigated two biological wastewater treatment reactors designed
      to recover potable water for a spacefaring crew being tested at Johnson Space
      Center. The experiment (Lunar-Mars Life Support Test Project-Phase III) consisted
      of four crew members confined in a test chamber for 91 days. In order to recycle
      all water during the experiment, an immobilized cell bioreactor (ICB) was
      employed for organic carbon removal and a trickling filter bioreactor (TFB) was
      utilized for ammonia removal, followed by physical-chemical treatment. In this
      study, the spatial distribution of various microorganisms within each bioreactor
      was analyzed by using biofilm samples taken from four locations in the ICB and
      three locations in the TFB. Three target genes were used for characterization of
      bacteria: the 16S rRNA gene for the total bacterial community, the ammonia
      monooxygenase (amoA) gene for ammonia-oxidizing bacteria, and the nitrous oxide
      reductase (nosZ) gene for denitrifying bacteria. A combination of terminal
      restriction fragment length polymorphism (T-RFLP), sequence, and phylogenetic
      analyses indicated that the microbial community composition in the ICB and the
      TFB consisted mainly of Proteobacteria, low-G+C gram-positive bacteria, and a
      Cytophaga-Flexibacter-Bacteroides group. Fifty-seven novel 16S rRNA genes, 8
      novel amoA genes, and 12 new nosZ genes were identified in this study. Temporal
      shifts in the species composition of total bacteria in both the ICB and the TFB
      and ammonia-oxidizing and denitrifying bacteria in the TFB were also detected
      when the biofilms were compared with the inocula after 91 days. This result
      suggests that specific microbial populations were either brought in by the crew
      or enriched in the reactors during the course of operation.

PMID- 11976100
TI  - Mechanisms for accessing insoluble Fe(III) oxide during dissimilatory Fe(III)
      reduction by Geothrix fermentans.
AB  - Mechanisms for Fe(III) oxide reduction were investigated in Geothrix fermentans,
      a dissimilatory Fe(III)-reducing microorganism found within the Fe(III) reduction
      zone of subsurface environments. Culture filtrates of G. fermentans stimulated
      the reduction of poorly crystalline Fe(III) oxide by washed cell suspensions,
      suggesting that G. fermentans released one or more extracellular compounds that
      promoted Fe(III) oxide reduction. In order to determine if G. fermentans released
      electron-shuttling compounds, poorly crystalline Fe(III) oxide was incorporated
      into microporous alginate beads, which prevented contact between G. fermentans
      and the Fe(III) oxide. G. fermentans reduced the Fe(III) within the beads,
      suggesting that one of the compounds that G. fermentans releases is an electron
      shuttling compound that can transfer electrons from the cell to Fe(III) oxide
      that is not in contact with the organism. Analysis of culture filtrates by thin
      layer chromatography suggested that the electron shuttle has characteristics
      similar to those of a water-soluble quinone. Analysis of filtrates by ion
      chromatography demonstrated that there was as much as 250 microM dissolved
      Fe(III) in cultures of G. fermentans growing with Fe(III) oxide as the electron
      acceptor, suggesting that G. fermentans released one or more compounds capable of
      chelating and solubilizing Fe(III). Solubilizing Fe(III) is another strategy for
      alleviating the need for contact between cells and Fe(III) oxide for Fe(III)
      reduction. This is the first demonstration of a microorganism that, in defined
      medium without added electron shuttles or chelators, can reduce Fe(III) derived
      from Fe(III) oxide without directly contacting the Fe(III) oxide. These results
      are in marked contrast to those with Geobacter metallireducens, which does not
      produce electron shuttles or Fe(III) chelators. These results demonstrate that
      phylogenetically distinct Fe(III)-reducing microorganisms may use significantly
      different strategies for Fe(III) reduction. Thus, it is important to know which
      Fe(III)-reducing microorganisms predominate in a given environment in order to
      understand the mechanisms for Fe(III) reduction in the environment of interest.

PMID- 11976101
TI  - Enrichment of members of the family Geobacteraceae associated with stimulation of
      dissimilatory metal reduction in uranium-contaminated aquifer sediments.
AB  - Stimulating microbial reduction of soluble U(VI) to insoluble U(IV) shows promise
      as a strategy for immobilizing uranium in uranium-contaminated subsurface
      environments. In order to learn more about which microorganisms might be involved
      in U(VI) reduction in situ, the changes in the microbial community when U(VI)
      reduction was stimulated with the addition of acetate were monitored in sediments
      from three different uranium-contaminated sites in the floodplain of the San Juan
      River in Shiprock, N.Mex. In all three sediments U(VI) reduction was accompanied
      by concurrent Fe(III) reduction and a dramatic enrichment of microorganisms in
      the family Geobacteraceae, which are known U(VI)- and Fe(III)-reducing
      microorganisms. At the point when U(VI) reduction and Fe(III) reduction were
      nearing completion, Geobacteraceae accounted for ca. 40% of the 16S ribosomal DNA
      (rDNA) sequences recovered from the sediments with bacterial PCR primers, whereas
      Geobacteraceae accounted for fewer than 5% of the 16S rDNA sequences in control
      sediments that were not amended with acetate and in which U(VI) and Fe(III)
      reduction were not stimulated. Between 55 and 65% of these Geobacteraceae
      sequences were most similar to sequences from Desulfuromonas species, with the
      remainder being most closely related to Geobacter species. Quantitative analysis
      of Geobacteraceae sequences with most-probable-number PCR and TaqMan analyses
      indicated that the number of Geobacteraceae sequences increased from 2 to 4
      orders of magnitude over the course of U(VI) and Fe(III) reduction in the acetate
      amended sediments from the three sites. No increase in Geobacteraceae sequences
      was observed in control sediments. In contrast to the predominance of
      Geobacteraceae sequences, no sequences related to other known Fe(III)-reducing
      microorganisms were detected in sediments. These results compare favorably with
      an increasing number of studies which have demonstrated that Geobacteraceae are
      important components of the microbial community in a diversity of subsurface
      environments in which Fe(III) reduction is an important process. The combination
      of these results with the finding that U(VI) reduction takes place during Fe(III)
      reduction and prior to sulfate reduction suggests that Geobacteraceae will be
      responsible for much of the Fe(III) and U(VI) reduction during uranium
      bioremediation in these sediments.

PMID- 11976102
TI  - Characterization of a class II defective transposon carrying two haloacetate
      dehalogenase genes from Delftia acidovorans plasmid pUO1.
AB  - The two haloacetate dehalogenase genes, dehH1 and dehH2, on the 65-kb plasmid
      pUO1 from Delftia acidovorans strain B were found to be located on transposable
      elements. The dehH2 gene was carried on an 8.9-kb class I composite transposon
      (TnHad1) that was flanked by two directly repeated copies of IS1071, IS1071L and
      IS1071R. The dehH1 gene was also flanked by IS1071L and a truncated version of
      IS1071 (IS1071N). TnHad1, dehH1, and IS1071N were located on a 15.6-kb class II
      transposon (TnHad2) whose terminal inverted repeats and res site showed high
      homology with those of the Tn21-related transposons. TnHad2 was defective in
      transposition because of its lacking the transposase and resolvase genes. TnHad2
      could transpose when the Tn21-encoded transposase and resolvase were supplied in
      trans. These results demonstrated that Tn Had2 is a defective Tn21-related
      transposon carrying another class I catabolic transposon.

PMID- 11976103
TI  - Genomic subtraction to identify and characterize sequences of Shiga toxin
      producing Escherichia coli O91:H21.
AB  - To identify Shiga toxin-producing Escherichia coli genes associated with severe
      human disease, a genomic subtraction technique was used with hemolytic-uremic
      syndrome-associated O91:H21 strain CH014 and O6:H10 bovine strains. The method
      was adapted to the Shiga toxin-producing E. coli genome: three rounds of
      subtraction were used to isolate DNA fragments specific to strain CH014. The
      fragments were characterized by genetic support analysis, sequencing, and
      hybridization to the genome of a collection of Shiga toxin-producing E. coli
      strains. A total of 42 fragments were found, 19 of which correspond to previously
      identified unique DNA sequences in the enterohemorrhagic E. coli EDL933 reference
      strain, including 7 fragments corresponding to prophage sequences and others
      encoding candidate virulence factors, such a SepA homolog protein and a fimbrial
      usher protein. In addition, the subtraction procedure yielded plasmid-related
      sequences from Shigella flexneri and enteropathogenic and Shiga toxin-producing
      E. coli virulence plasmids. We found that lateral gene transfer is extensive in
      strain CH014, and we discuss the role of genomic mobile elements, especially
      bacteriophages, in the evolution and possible transfer of virulence determinants.

PMID- 11976104
TI  - Ochratoxin production by the Aspergillus ochraceus group and Aspergillus
      alliaceus.
AB  - Ochratoxin A is a toxic and carcinogenic fungal secondary metabolite; its
      presence in foods is increasingly regulated. Various fungi are known to produce
      ochratoxins, but it is not known which species produce ochratoxins consistently
      and which species cause ochratoxin contamination of various crops. We isolated
      fungi in the Aspergillus ochraceus group (section Circumdati) and Aspergillus
      alliaceus from tree nut orchards, nuts, and figs in California. A total of 72
      isolates were grown in potato dextrose broth and yeast extract-sucrose broth for
      10 days at 30 degrees C and tested for production of ochratoxin A in vitro by
      high-pressure liquid chromatography. Among isolates from California figs, tree
      nuts, and orchards, A. ochraceus and Aspergillus melleus were the most common
      species. No field isolates of A. ochraceus or A. melleus produced ochratoxin A
      above the level of detection (0.01 microg/ml). All A. alliaceus isolates produced
      ochratoxin A, up to 30 microg/ml. We examined 50,000 figs for fungal infections
      and measured ochratoxin content in figs with visible fungal colonies. Pooled figs
      infected with A. alliaceus contained ochratoxin A, figs infected with the A.
      ochraceus group had little or none, and figs infected with Penicillium had none.
      These results suggest that the little-known species A. alliaceus is an important
      ochratoxin-producing fungus in California and that it may be responsible for the
      ochratoxin contamination occasionally observed in figs.

PMID- 11976106
TI  - Extracellular polysaccharides of Rhodococcus rhodochrous S-2 stimulate the
      degradation of aromatic components in crude oil by indigenous marine bacteria.
AB  - Rhodococcus rhodochrous S-2 produces extracellular polysaccharides (S-2 EPS)
      containing D-glucose, D-galactose, D-mannose, D-glucuronic acid, and lipids,
      which is important to the tolerance of this strain to an aromatic fraction of
      (AF) Arabian light crude oil (N. Iwabuchi, N. Sunairi, H. Anzai, M. Nakajima, and
      S. Harayama, Appl. Environ. Microbiol. 66:5073-5077, 2000). In the present study,
      we examined the effects of S-2 EPS on the growth of indigenous marine bacteria on
      AF. Indigenous bacteria did not grow significantly in seawater containing AF even
      when nitrogen, phosphorus, and iron nutrients were supplemented. The addition of
      S-2 EPS to seawater containing nutrients and AF resulted in the emulsification of
      AF, promotion of the growth of indigenous bacteria, and enhancement of the
      degradation of AF by the bacteria. PCR-denaturing gradient gel electrophoresis
      analyses show that addition of S-2 EPS to the seawater containing nutrients and
      AF changed the composition of the bacterial populations in the seawater and that
      bacteria closely related to the genus Cycloclasticus became the major population.
      These results suggest that Cycloclasticus was responsible for the degradation of
      hydrocarbons in AF. The effects of 15 synthetic surfactants on the degradation of
      AF by indigenous marine bacteria were also examined, but enhancement of the
      degradation of AF was not significant. S-2 EPS was hence the most effective of
      the surfactants tested in promoting the biodegradation of AF and may thus be an
      attractive agent to use in the bioremediation of oil-contaminated marine
      environments.

PMID- 11976105
TI  - Purification and characterization of a surface protein from Lactobacillus
      fermentum 104R that binds to porcine small intestinal mucus and gastric mucin.
AB  - An adhesion-promoting protein involved in the binding of Lactobacillus fermentum
      strain 104R to small intestinal mucus from piglets and to partially purified
      gastric mucin was isolated and characterized. Spent culture supernatant fluid and
      bacterial cell wall extracts were fractionated by ammonium sulfate precipitation
      and gel filtration. The active fraction was purified by affinity chromatography.
      The adhesion-promoting protein was detected in the fractions by adhesion
      inhibition and dot blot assays and visualized by polyacrylamide gel
      electrophoresis (PAGE), sodium dodecyl sulfate-PAGE, and Western blotting with
      horseradish peroxidase-labeled mucus and mucin. The active fraction was
      characterized by estimating the relative molecular weight and by assessing the
      presence of carbohydrates in, and heat sensitivity of, the active region of the
      adhesion-promoting protein. The purified protein was digested with porcine
      trypsin, and the peptides were purified in a SMART system. The peptides were
      tested for adhesion to horseradish peroxidase-labeled mucin by using the dot blot
      adhesion assay. Peptides which bound mucin were sequenced. It was shown that the
      purified adhesion-promoting protein on the cell surface of L. fermentum 104R is
      extractable with 1 M LiCl and low concentrations of lysozyme but not with 0.2 M
      glycine. The protein could be released to the culture supernatant fluid after 24
      h of growth and had affinity for both small intestinal mucus and gastric mucin.
      In the native state this protein was variable in size, and it had a molecular
      mass of 29 kDa when denatured. The denatured protein did not contain carbohydrate
      moieties and was not heat sensitive. Alignment of amino acids of the adhering
      peptides with sequences deposited in the EMBL data library showed poor homology
      with previously published sequences. The protein represents an important molecule
      for development of probiotics.

PMID- 11976107
TI  - Bacillus probiotics: spore germination in the gastrointestinal tract.
AB  - Spores of Bacillus species are being used commercially as probiotics and
      competitive exclusion agents. Unlike the more commonly used Lactobacillus-type
      probiotics, spores are dormant life forms. To address how spore probiotics might
      function we have investigated whether spores can germinate in the
      gastrointestinal tract by using a murine model. Using a genetically engineered
      chimeric gene, ftsH-lacZ, which is strongly expressed only in vegetative cells,
      we have developed a sensitive competitive reverse transcription-PCR assay which
      has enabled detection of as few as 10(2) vegetative bacteria in the mouse gut.
      Using this method we have administered doses of ftsH-lacZ spores to groups of
      mice and shown that spores can germinate in significant numbers in the jejunum
      and ileum. The levels of detection we obtained suggest that spores may colonize
      the small intestine, albeit briefly.

PMID- 11976109
TI  - Cre-loxP recombination system for large genome rearrangements in Lactococcus
      lactis.
AB  - We have used a new genetic strategy based on the Cre-loxP recombination system to
      generate large chromosomal rearrangements in Lactococcus lactis. Two loxP sites
      were sequentially integrated in inverse order into the chromosome either at
      random locations by transposition or at fixed points by homologous recombination.
      The recombination between the two chromosomal loxP sites was highly efficient
      (approximately 1 x 10(-1)/cell) when the Cre recombinase was provided in trans,
      and parental- or inverted-type chromosomal structures were isolated after removal
      of the Cre recombinase. The usefulness of this approach was demonstrated by
      creating three large inversions of 500, 1,115, and 1,160 kb in size that modified
      the lactococcal genome organization to different extents. The Cre-loxP
      recombination system described can potentially be used for other gram-positive
      bacteria without further modification.

PMID- 11976108
TI  - Synthesis of pyruvate dehydrogenase in Staphylococcus aureus is stimulated by
      osmotic stress.
AB  - The pyruvate dehydrogenase multienzyme complex (PDHC) was found to be upregulated
      by osmotic stress in the osmotolerant pathogen Staphylococcus aureus.
      Upregulation was detectable in the levels of both activity and protein and was
      judged to be about fourfold when sodium chloride was used to adjust the water
      activity (a(w)) of the growth medium to 0.94. The upregulation of the PDHC was
      also found to be humectant dependent and was greatest when impermeant,
      nonmetabolizable humectants were used to adjust a(w). Further experiments
      provided evidence that in addition to osmotic upregulation, the PDHC complex is
      also subject to catabolite repression, thus providing a possible explanation for
      the observation that high concentrations of carbohydrates are generally more
      inhibitory to the growth of this bacterial pathogen than are high concentrations
      of salts.

PMID- 11976110
TI  - Transformation of isopropylamine to L-alaninol by Pseudomonas sp. strain KIE171
      involves N-glutamylated intermediates.
AB  - Pseudomonas sp. strain KIE171 was able to grow with isopropylamine or L-alaninol
      [S-(+)-2-amino-1-propanol] as the sole carbon source, but not with D-alaninol. To
      investigate the hypothesis that L-alaninol is an intermediate in the degradation
      of isopropylamine, two mini-Tn5 mutants unable to utilize both isopropylamine and
      L-alaninol were isolated. Whereas mutant KIE171-BI transformed isopropylamine to
      L-alaninol, mutant KIE171-BII failed to do so. The two genes containing a
      transposon insertion were cloned, and the DNA regions flanking the insertions
      were sequenced. Two clusters, one comprising eight ipu (isopropylamine
      utilization) genes (ipuABCDEFGH) and the other encompassing two genes (ipuI and
      orf259), were identified. Comparisons of sequences of the deduced Ipu proteins
      and those in the database suggested that isopropylamine is transported into the
      cytoplasm by a putative permease, IpuG. The next step, the formation of gamma
      glutamyl-isopropylamide from isopropylamine, ATP, and L-glutamate, was shown to
      be catalyzed by IpuC, a gamma-glutamylamide synthetase. gamma-Glutamyl
      isopropylamide is then subjected to stereospecific monooxygenation by the
      hypothetical four-component system IpuABDE, thereby yielding gamma-glutamyl-L
      alaninol [gamma(L-glutamyl)-L-hydroxy-isopropylamide]. Enzymatic hydrolysis by a
      hydrolase, IpuF, was shown to finally liberate L-alaninol and to regenerate L
      glutamate. No gene(s) encoding an enzyme for the next step in the degradation of
      isopropylamine was found in the ipu clusters. Presumably, L-alaninol is oxidized
      by an alcohol dehydrogenase to yield L-2-aminopropionaldehyde or it is deaminated
      by an ammonia lyase to propionaldehyde. Genetic evidence indicated that the
      aldehyde formed is then further oxidized by the hypothetical aldehyde
      dehydrogenases IpuI and IpuH to either L-alanine or propionic acid, compounds
      which can be processed by reactions of the intermediary metabolism.

PMID- 11976111
TI  - Salmonella enterica infections in market swine with and without transport and
      holding.
AB  - The objective of this study was to compare, by using identical sample types, the
      Salmonella enterica prevalences and serovar diversities between pigs necropsied
      on the farm and those necropsied at the abattoir after transport and holding. We
      necropsied 567 market weight pigs (>70 kg) from six herds. Pigs were alternately
      assigned to be necropsied on the farm or at the abattoir. One-half of the group
      was sent in clean, disinfected trailers to slaughter at a commercial abattoir.
      After transport (mean distance, 169 km) and 2 to 3 h of holding in antemortem
      pens, these pigs were necropsied. The 50 pigs remaining on the farm were
      necropsied the following day. The same sample types and amounts were collected
      for S. enterica culture at both locations. Results show a sevenfold-higher (P <
      0.001) S. enterica isolation rate from pigs necropsied at the abattoir (39.9%;
      114 of 286) than from those necropsied on the farm (5.3%; 15 of 281). This
      difference was also observed for each individual herd. All sample types showed a
      significantly higher prevalence when comparing abattoir to on-farm collection,
      respectively: lymph nodes, 9.15 versus 3.6%; cecal contents, 13.6 versus 1.8%; 1
      g of fecal matter, 25.2 versus 0.7%. Recovery of additional serovars at the
      abattoir suggests the pigs are receiving S. enterica from extra-farm sources.
      This study demonstrates that rapid infection during transport, and particularly
      during holding, is a major reason for increased S. enterica prevalence in swine.
      This finding identifies the holding pen as an important S. enterica control point
      in the pork production chain.

PMID- 11976112
TI  - Analysis of Streptococcus mutans proteins modulated by culture under acidic
      conditions.
AB  - Streptococcus mutans, a major etiological agent of dental caries, causes
      demineralization of the tooth tissue due to the formation of acids from dietary
      carbohydrates. Dominant among the virulence determinants of this organism are
      aciduricity and acidogenicity, the abilities to grow at low pH and to produce
      acid, respectively. The mechanisms underlying the ability of S. mutans to survive
      and proliferate at low pH are currently under investigation. In this study we
      cultured S. mutans at pH 5.2 or 7.0 and extracted soluble cellular proteins.
      These were analyzed using high-resolution two-dimensional gel electrophoresis,
      and replicate maps of proteins expressed under each of the two conditions were
      generated. Proteins with modulated expression at low pH, as judged by a change in
      the relative integrated optical density, were excised and digested with trypsin
      by using an in-gel protocol. Tryptic digests were analyzed using matrix-assisted
      laser desorption ionization mass spectrometry to generate peptide mass
      fingerprints, and these were used to assign putative functions according to their
      homology with the translated sequences in the S. mutans genomic database. Thirty
      individual proteins exhibited altered expression as a result of culture of S.
      mutans at low pH. Up-regulated proteins (n = 18) included neutral endopeptidase,
      phosphoglucomutase, 60-kDa chaperonin, cell division proteins, enolase, lactate
      dehydrogenase, fructose bisphosphate aldolase, acetoin reductase, superoxide
      dismutase, and lactoylglutathione lyase. Proteins down-regulated at pH 5.2 (n =
      12) included protein translation elongation factors G, Tu, and Ts, DnaK, small
      subunit ribosomal protein S1P, large-subunit ribosomal protein L12P, and
      components of both phosphoenolpyruvate:protein phosphotransferase and multiple
      sugar binding transport systems. The identification of proteins differentially
      expressed following growth at low pH provides new information regarding the
      mechanisms of survival and has identified new target genes for mutagenesis
      studies to further assess their physiological significance.

PMID- 11976113
TI  - Improved culturability of soil bacteria and isolation in pure culture of novel
      members of the divisions Acidobacteria, Actinobacteria, Proteobacteria, and
      Verrucomicrobia.
AB  - The culturability of bacteria in the bulk soil of an Australian pasture was
      investigated by using nutrient broth at 1/100 of its normal concentration (dilute
      nutrient broth [DNB]) as the growth medium. Three-tube most-probable-number
      serial dilution culture resulted in a mean viable count that was only 1.4% of the
      mean microscopically determined total cell count. Plate counts with DNB
      solidified with agar and with gellan gum resulted in viable counts that were 5.2
      and 7.5% of the mean microscopically determined total cell count, respectively.
      Prior homogenization of the soil sample with an ultrasonic probe increased the
      viable count obtained by using DNB solidified with gellan gum to 14.1% of the
      mean microscopically determined cell count. A microscopic examination of the cell
      aggregates that remained after sonication revealed that the potential CFU count
      was only 70.4% of the total cell count, due to cells occurring as pairs or in
      clumps of three or more cells. Staining with SYTO 9 plus propidium iodide
      indicated that 91.3% of the cells in sonicated soil samples were potentially
      viable. Together, these findings suggest that the maximum achievable CFU count
      may be as low as 64.3% of the total cell count. Thirty isolates obtained from
      plate counting experiments performed with DNB as the growth medium were
      identified by comparative analysis of partial 16S rRNA gene sequences. A large
      proportion of these isolates represent the first known isolates of globally
      distributed groups of soil bacteria belonging to novel lineages within the
      divisions Actinobacteria, Acidobacteria, Proteobacteria, and Verrucomicrobia.

PMID- 11976114
TI  - Modulation of gene expression made easy.
AB  - A new approach for modulating gene expression, based on randomization of promoter
      (spacer) sequences, was developed. The method was applied to chromosomal genes in
      Lactococcus lactis and shown to generate libraries of clones with broad ranges of
      expression levels of target genes. In one example, overexpression was achieved by
      introducing an additional gene copy into a phage attachment site on the
      chromosome. This resulted in a series of strains with phosphofructokinase
      activities from 1.4 to 11 times the wild-type activity level. In this example,
      the pfk gene was cloned upstream of a gusA gene encoding beta-glucuronidase,
      resulting in an operon structure in which both genes are transcribed from a
      common promoter. We show that there is a linear correlation between the
      expressions of the two genes, which facilitates screening for mutants with
      suitable enzyme activities. In a second example, we show that the method can be
      applied to modulating the expression of native genes on the chromosome. We
      constructed a series of strains in which the expression of the las operon,
      containing the genes pfk, pyk, and ldh, was modulated by integrating a truncated
      copy of the pfk gene. Importantly, the modulation affected the activities of all
      three enzymes to the same extent, and enzyme activities ranging from 0.5 to 3.5
      times the wild-type level were obtained.

PMID- 11976115
TI  - Enzymatic synthesis of aminoglycoside antibiotics: novel adenosylmethionine:2
      deoxystreptamine N-methyltransferase activities in hygromycin B- and
      spectinomycin-producing Streptomyces spp. and uses of the methylated products.
AB  - Aminocyclitols structurally related to streptamine, a 1,3-diaminocyclitol, are
      common components of the RNA-binding aminoglycoside antibiotics. The respective
      aminocyclitol cores of hygromycin B and spectinomycin are N(3)-methyl-2-deoxy-D
      streptamine and N(1),N(3)-dimethyl-2-epi-streptamine. Adenosyl[methyl
      (14)C]methionine:2-deoxystreptamine N-methyltransferase activities were detected
      in extracts of early-stationary-phase mycelia of the hygromycin B producer
      Streptomyces hygroscopicus subsp. hygroscopicus ATCC 27438 and the spectinomycin
      producer Streptomyces flavopersicus ATCC 19756. Extracts of both strains
      methylated the N(1)- and N(3)-amino groups of 2-deoxystreptamine, streptamine,
      and 2-epi-streptamine; the N(1)-amino group of N(3)-methyl-2-deoxy-D-streptamine,
      and the N(3)-amino group of N(1)-ethyl-2-deoxy-D-streptamine, the semisynthetic
      aminocyclitol of netilmicin. The mono[(14)C]methyl derivatives of 2
      deoxystreptamine, streptamine, and 2-epi-streptamine were excellent substrates
      for L-glutamine:aminocyclitol aminotransferase and thereby provided a sensitive
      assay for derepression of this key enzyme, a generic biosynthetic marker that we
      have shown to be the only enzyme common to the biosyntheses of all major
      aminoglycoside antibiotics. Other prospective uses for these methyl-labeled 2
      deoxystreptamine analogs are also described.

PMID- 11976116
TI  - Enhanced accumulation and changed monomer composition in polyhydroxyalkanoate
      (PHA) copolyester by in vitro evolution of Aeromonas caviae PHA synthase.
AB  - By in vitro evolution experiment, we have first succeeded in acquiring higher
      active mutants of a synthase that is a key enzyme essential for bacterial
      synthesis of biodegradable polyester, polyhydroxyalkanoate (PHA). Aeromonas
      caviae FA440 synthase, termed PhaC(Ac), was chosen as a good target for
      evolution, since it can synthesize a PHA random copolyester of 3-hydroxybutyrate
      and 3-hydroxyhexanoate [P(3HB-co-3HHx)] that is a tough and flexible material
      compared to polyhydroxybutyrate (PHB) homopolyester. The in vitro enzyme
      evolution system consists of PCR-mediated random mutagenesis targeted to a
      limited region of the phaC(Ac) gene and screening mutant enzymes with higher
      activities based on two types of polyester accumulation system by using
      Escherichia coli for the synthesis of PHB (by JM109 strain) (S. Taguchi, A.
      Maehara, K. Takase, M. Nakahara, H. Nakamura, and Y. Doi, FEMS Microbiol. Lett.
      198:65-71, 2001) and of P(3HB-co-3HHx) [by LS5218 [fadR601 atoC(Con)] strain].
      The expression vector for the phaC(Ac) gene, together with monomer-supplying
      enzyme genes, was designed to synthesize PHB homopolyester from glucose and P(3HB
      co-3HHx) copolyester from dodecanoate. Two evolved mutant enzymes, termed E2-50
      and T3-11, screened through the evolution system exhibited 56 and 21% increases
      in activity toward 3HB-coenzyme A, respectively, and consequently led to enhanced
      accumulation (up to 6.5-fold content) of P(3HB-co-3HHx) in the recombinant LS5218
      strains. Two single mutations in the mutants, N149S for E2-50 and D171G for T3
      11, occurred at positions that are not highly conserved among the PHA synthase
      family. It should be noted that increases in the 3HHx fraction (up to 16 to 18
      mol%) were observed for both mutants compared to the wild type (10 mol%).

PMID- 11976117
TI  - Identification, detection, and enumeration of human bifidobacterium species by
      PCR targeting the transaldolase gene.
AB  - Methods that enabled the identification, detection, and enumeration of
      Bifidobacterium species by PCR targeting the transaldolase gene were tested.
      Bifidobacterial species isolated from the feces of human adults and babies were
      identified by PCR amplification of a 301-bp transaldolase gene sequence and
      comparison of the relative migrations of the DNA fragments in denaturing gradient
      gel electrophoresis (DGGE). Two subtypes of Bifidobacterium longum, five subtypes
      of Bifidobacterium adolescentis, and two subtypes of Bifidobacterium
      pseudocatenulatum could be differentiated using PCR-DGGE. Bifidobacterium
      angulatum and B. catenulatum type cultures could not be differentiated from each
      other. Bifidobacterial species were also detected directly in fecal samples by
      this combination of PCR and DGGE. The number of species detected was less than
      that detected by PCR using species-specific primers targeting 16S ribosomal DNA
      (rDNA). Real-time quantitative PCR targeting a 110-bp transaldolase gene sequence
      was used to enumerate bifidobacteria in fecal samples. Real-time quantitative PCR
      measurements of bifidobacteria in fecal samples from adults correlated well with
      results obtained by culture when either a 16S rDNA sequence or the transaldolase
      gene sequence was targeted. In the case of samples from infants, 16S rDNA
      targeted PCR was superior to PCR targeting the transaldolase gene for the
      quantification of bifidobacterial populations.

PMID- 11976118
TI  - Incidence of Mycobacterium paratuberculosis in bulk raw and commercially
      pasteurized cows' milk from approved dairy processing establishments in the
      United Kingdom.
AB  - Over a 17-month period (March 1999 to July 2000), a total of 814 cows' milk
      samples, 244 bulk raw and 567 commercially pasteurized (228 whole, 179 semi-skim,
      and 160 skim), from 241 approved dairy processing establishments throughout the
      United Kingdom were tested for the presence of Mycobacterium paratuberculosis by
      immunomagnetic PCR (to detect all cells living and dead) and culture (to detect
      viable cells). Overall, M. paratuberculosis DNA was detected by immunomagnetic
      PCR in 19 (7.8%; 95% confidence interval, 4.3 to 10.8%) and 67 (11.8%; 95%
      confidence interval, 9.0 to 14.2%) of the raw and pasteurized milk samples,
      respectively. Confirmed M. paratuberculosis isolates were cultured from 4 (1.6%;
      95% confidence interval, 0.04 to 3.1%) and 10 (1.8%; 95% confidence interval, 0.7
      to 2.8%) of the raw and pasteurized milk samples, respectively, following
      chemical decontamination with 0.75% (wt/vol) cetylpyridinium chloride for 5 h.
      The 10 culture-positive pasteurized milk samples were from just 8 (3.3%) of the
      241 dairy processing establishments that participated in the survey. Seven of the
      culture-positive pasteurized milk samples had been heat treated at 72 to 74
      degrees C for 15 s; the remainder had been treated at 72 to 75 degrees C for the
      extended holding time of 25 s. When typed by restriction fragment length
      polymorphism and pulsed-field gel electrophoresis methods, some of the milk
      isolates were shown to be types distinct from those of laboratory strains in
      regular use within the testing laboratory. From information gathered at the time
      of milk sample collection, all indications were that pasteurization had been
      carried out effectively at all of the culture-positive dairies. That is,
      pasteurization time and temperature conditions complied with the legal minimum
      high-temperature, short-time process; all pasteurized milk samples tested
      phosphatase negative; and post-process contamination was considered unlikely to
      have occurred. It was concluded that viable M. paratuberculosis is occasionally
      present at low levels in commercially pasteurized cows' milk in the United
      Kingdom.

PMID- 11976119
TI  - Melanin production and use as a soluble electron shuttle for Fe(III) oxide
      reduction and as a terminal electron acceptor by Shewanella algae BrY.
AB  - Dissimilatory metal-reducing bacteria (DMRB) utilize numerous compounds as
      terminal electron acceptors, including insoluble iron oxides. The mechanism(s) of
      insoluble-mineral reduction by DMRB is not well understood. Here we report that
      extracellular melanin is produced by Shewanella algae BrY. The extracted melanin
      served as the sole terminal electron acceptor. Upon reduction the reduced,
      soluble melanin reduced insoluble hydrous ferric oxide in the absence of
      bacteria, thus demonstrating that melanin produced by S. algae BrY is a soluble
      Fe(III)-reducing compound. In the presence of bacteria, melanin acted as an
      electron conduit to Fe(III) minerals and increased Fe(III) mineral reduction
      rates. Growth of S. algae BrY occurred in anaerobic minimal medium supplemented
      with melanin extracted from previously grown aerobic cultures of S. algae BrY.
      Melanin produced by S. algae BrY imparts increased versatility to this organism
      as a soluble Fe(III) reductant, an electron conduit for iron mineral reduction,
      and a sole terminal electron acceptor that supports growth.

PMID- 11976120
TI  - Diversity and ubiquity of bacteria capable of utilizing humic substances as
      electron donors for anaerobic respiration.
AB  - Previous studies have demonstrated that reduced humic substances (HS) can be
      reoxidized by anaerobic bacteria such as Geobacter, Geothrix, and Wolinella
      species with a suitable electron acceptor; however, little is known of the
      importance of this metabolism in the environment. Recently we investigated this
      metabolism in a diversity of environments including marine and aquatic sediments,
      forest soils, and drainage ditch soils. Most-probable-number enumeration studies
      were performed using 2,6-anthrahydroquinone disulfonate (AHDS), an analog for
      reduced HS, as the electron donor with nitrate as the electron acceptor.
      Anaerobic organisms capable of utilizing reduced HS as an electron donor were
      found in all environments tested and ranged from a low of 2.31 x 10(1) in aquifer
      sediments to a high of 9.33 x 10(6) in lake sediments. As part of this study we
      isolated six novel organisms capable of anaerobic AHDS oxidation. All of the
      isolates coupled the oxidation of AHDS to the reduction of nitrate with acetate
      (0.1 mM) as the carbon source. In the absence of cells, no AHDS oxidation was
      apparent, and in the absence of AHDS, no cell density increase was observed.
      Generally, nitrate was reduced to N(2). Analysis of the AHDS and its oxidized
      form, 2,6-anthraquinone disulfonate (AQDS), in the medium during growth revealed
      that the anthraquinone was not being biodegraded as a carbon source and was
      simply being oxidized as an energy source. Determination of the AHDS oxidized and
      nitrate reduced accounted for 109% of the theoretical electron transfer. In
      addition to AHDS, all of these isolates could also couple the oxidation of
      reduced humic substances to the reduction of nitrate. No HS oxidation occurred in
      the absence of cells and in the absence of a suitable electron acceptor,
      demonstrating that these organisms were capable of utilizing natural HS as an
      energy source and that AHDS serves as a suitable analog for studying this
      metabolism. Alternative electron donors included simple volatile fatty acids such
      as propionate, butyrate, and valerate as well as simple organic acids such as
      lactate and pyruvate. Analysis of the complete sequences of the 16S rRNA genes
      revealed that the isolates were not closely related to each other and were
      phylogenetically diverse, with members in the alpha, beta, gamma, and delta
      subdivisions of the PROTEOBACTERIA: Most of the isolates were closely related to
      known genera not previously recognized for their ability to couple growth to HS
      oxidation, while one of the isolates represented a new genus in the delta
      subclass of the PROTEOBACTERIA: The results presented here demonstrate that
      microbial oxidation of HS is a ubiquitous metabolism in the environment. This
      study represents the first description of HS-oxidizing isolates and demonstrates
      that microorganisms capable of HS oxidation are phylogenetically diverse.

PMID- 11976122
TI  - Engineering the Rhizobium leguminosarum bv. viciae hydrogenase system for
      expression in free-living microaerobic cells and increased symbiotic hydrogenase
      activity.
AB  - Rhizobium leguminosarum bv. viciae UPM791 induces hydrogenase activity in pea
      (Pisum sativum L.) bacteroids but not in free-living cells. The symbiotic
      induction of hydrogenase structural genes (hupSL) is mediated by NifA, the
      general regulator of the nitrogen fixation process. So far, no culture conditions
      have been found to induce NifA-dependent promoters in vegetative cells of this
      bacterium. This hampers the study of the R. leguminosarum hydrogenase system. We
      have replaced the native NifA-dependent hupSL promoter with the FnrN-dependent
      fixN promoter, generating strain SPF25, which expresses the hup system in
      microaerobic free-living cells. SPF25 reaches levels of hydrogenase activity in
      microaerobiosis similar to those induced in UPM791 bacteroids. A sixfold increase
      in hydrogenase activity was detected in merodiploid strain SPF25(pALPF1). A time
      course induction of hydrogenase activity in microaerobic free-living cells of
      SPF25(pALPF1) shows that hydrogenase activity is detected after 3 h of
      microaerobic incubation. Maximal hydrogen uptake activity was observed after 10 h
      of microaerobiosis. Immunoblot analysis of microaerobically induced SPF25(pALPF1)
      cell fractions indicated that the HupL active form is located in the membrane,
      whereas the unprocessed protein remains in the soluble fraction. Symbiotic
      hydrogenase activity of strain SPF25 was not impaired by the promoter
      replacement. Moreover, bacteroids from pea plants grown in low-nickel
      concentrations induced higher levels of hydrogenase activity than the wild-type
      strain and were able to recycle all hydrogen evolved by nodules. This constitutes
      a new strategy to improve hydrogenase activity in symbiosis.

PMID- 11976121
TI  - Identification of novel hexapeptides bioactive against phytopathogenic fungi
      through screening of a synthetic peptide combinatorial library.
AB  - The purpose of the present study was to improve the antifungal activity against
      selected phytopathogenic fungi of the previously identified hexapeptide PAF19. We
      describe some properties of a set of novel synthetic hexapeptides whose D-amino
      acid sequences were obtained through screening of a synthetic peptide
      combinatorial library in a positional scanning format. As a result of the
      screening, 12 putative bioactive peptides were identified, synthesized, and
      assayed. The peptides PAF26 (Ac-rkkwfw-NH(2)), PAF32 (Ac-rkwhfw-NH(2)), and PAF34
      (Ac-rkwlfw-NH(2)) showed stronger activity than PAF19 against isolates of
      Penicillium digitatum, Penicillium italicum, and Botrytis cinerea. PAF26 and
      PAF32, but not PAF34, were also active against Fusarium oxysporum. Penicillium
      expansum was less susceptible to all four PAF peptides, and only PAF34 showed
      weak activity against it. Assays were also conducted on nontarget organisms, and
      PAF26 and PAF32 showed much-reduced toxicity to Escherichia coli and
      Saccharomyces cerevisiae, demonstrating selectivity towards certain filamentous
      fungi. Thus, the data showed distinct activity profiles for peptides
      differentiated by just one or two residue substitutions. Our conclusion from this
      observation is that a specificity factor is involved in the activity of these
      short peptides. Furthermore, PAF26 and PAF32 displayed activities against P.
      digitatum, P. italicum, and B. cinerea similar to that of the hemolytic 26-amino
      acid melittin, but they did not show the high toxicity of melittin towards
      bacteria and yeasts. The four peptides acted additively, with no synergistic
      interactions among them, and PAF26 was shown to have improved activity over PAF19
      in in vivo orange fruit decay experiments.

PMID- 11976123
TI  - Energy-based dynamic model for variable temperature batch fermentation by
      Lactococcus lactis.
AB  - We developed a mechanistic mathematical model for predicting the progression of
      batch fermentation of cucumber juice by Lactococcus lactis under variable
      environmental conditions. In order to overcome the deficiencies of presently
      available models, we use a dynamic energy budget approach to model the dependence
      of growth on present as well as past environmental conditions. When parameter
      estimates from independent experimental data are used, our model is able to
      predict the outcomes of three different temperature shift scenarios. Sensitivity
      analyses elucidate how temperature affects the metabolism and growth of cells
      through all four stages of fermentation and reveal that there is a qualitative
      reversal in the factors limiting growth between low and high temperatures. Our
      model has an applied use as a predictive tool in batch culture growth. It has the
      added advantage of being able to suggest plausible and testable mechanistic
      assumptions about the interplay between cellular energetics and the modes of
      inhibition by temperature and end product accumulation.

PMID- 11976124
TI  - Quantitative analysis of cereulide, the emetic toxin of Bacillus cereus, produced
      under various conditions.
AB  - This paper describes a quantitative and sensitive chemical assay for cereulide,
      the heat-stable emetic toxin produced by Bacillus cereus. The methods previously
      available for measuring cereulide are bioassays that give a toxicity titer, but
      not an accurate concentration. The dose of cereulide causing illness in humans is
      therefore not known, and thus safety limits for cereulide cannot be indicated. We
      developed a quantitative and sensitive chemical assay for cereulide based on high
      performance liquid chromatography (HPLC) connected to ion trap mass spectrometry.
      This chemical assay and a bioassay based on boar sperm motility inhibition were
      calibrated with purified cereulide and with valinomycin, a structurally similar
      cyclic depsipeptide. The boar spermatozoan motility assay and chemical assay gave
      uniform results over a wide range of cereulide concentrations, ranging from 0.02
      to 230 microg ml(-1). The detection limit for cereulide and valinomycin by HPLC
      mass spectrometry was 10 pg per injection. The combined chemical and biological
      assays were used to define conditions and concentrations of cereulide formation
      by B. cereus strains F4810/72, NC7401, and F5881. Cereulide production commenced
      at the end of logarithmic growth, but was independent of sporulation. Production
      of cereulide was enhanced by incubation with shaking compared to static
      conditions. The three emetic B. cereus strains accumulated 80 to 166 microg of
      cereulide g(-1) (wet weight) when grown on solid medium. Strain NC7401
      accumulated up to 25 microg of cereulide ml(-1) in liquid medium at room
      temperature (21 +/- 1 degrees C) in 1 to 3 days, during the stationary growth
      phase when cell density was 2 x 10(8) to 6 x 10(8) CFU ml(-1). Cereulide
      production at temperatures at and below 8 degrees C or at 40 degrees C was
      minimal.

PMID- 11976125
TI  - Effects of amendment with ferrihydrite and gypsum on the structure and activity
      of methanogenic populations in rice field soil.
AB  - Methane emission from paddy fields may be reduced by the addition of electron
      acceptors to stimulate microbial populations competitive to methanogens. We have
      studied the effects of ferrihydrite and gypsum (CaSO(4). 2H(2)O) amendment on
      methanogenesis and population dynamics of methanogens after flooding of Italian
      rice field soil slurries. Changes in methanogen community structure were followed
      by archaeal small subunit (SSU) ribosomal DNA (rDNA)- and rRNA-based terminal
      restriction fragment length polymorphism analysis and by quantitative SSU rRNA
      hybridization probing. Under ferrihydrite amendment, acetate was consumed
      efficiently (<60 microM) and a rapid but incomplete inhibition of methanogenesis
      occurred after 3 days. In contrast to unamended controls, the dynamics of
      Methanosarcina populations were largely suppressed as indicated by rDNA and rRNA
      analysis. However, the low acetate availability was still sufficient for
      activation of Methanosaeta spp., as indicated by a strong increase of SSU rRNA
      but not of relative rDNA frequencies. Unexpectedly, rRNA amounts of the novel
      rice cluster I (RC-I) methanogens increased significantly, while methanogenesis
      was low, which may be indicative of transient energy conservation coupled to
      Fe(III) reduction by these methanogens. Under gypsum addition, hydrogen was
      rapidly consumed to low levels ( approximately 0.4 Pa), indicating the presence
      of a competitive population of hydrogenotrophic sulfate-reducing bacteria (SRB).
      This was paralleled by a suppressed activity of the hydrogenotrophic RC-I
      methanogens as indicated by the lowest SSU rRNA quantities detected in all
      experiments. Full inhibition of methanogenesis only became apparent when acetate
      was depleted to nonpermissive thresholds (<5 microM) after 10 days. Apparently, a
      competitive, acetotrophic population of SRB was not present initially, and hence,
      acetotrophic methanosarcinal populations were less suppressed than under
      ferrihydrite amendment. In conclusion, although methane production was inhibited
      effectively under both mitigation regimens, different methanogenic populations
      were either suppressed or stimulated, which demonstrates that functionally
      similar disturbances of an ecosystem may result in distinct responses of the
      populations involved.

PMID- 11976126
TI  - Metabolic commensalism and competition in a two-species microbial consortium.
AB  - We analyzed metabolic interactions and the importance of specific structural
      relationships in a benzyl alcohol-degrading microbial consortium comprising two
      species, Pseudomonas putida strain R1 and Acinetobacter strain C6, both of which
      are able to utilize benzyl alcohol as their sole carbon and energy source. The
      organisms were grown either as surface-attached organisms (biofilms) in flow
      chambers or as suspended cultures in chemostats. The numbers of CFU of P. putida
      R1 and Acinetobacter strain C6 were determined in chemostats and from the
      effluents of the flow chambers. When the two species were grown together in
      chemostats with limiting concentrations of benzyl alcohol, Acinetobacter strain
      C6 outnumbered P. putida R1 (500:1), whereas under similar growth conditions in
      biofilms, P. putida R1 was present in higher numbers than Acinetobacter strain C6
      (5:1). In order to explain this difference, investigations of microbial
      activities and structural relationships were carried out in the biofilms.
      Insertion into P. putida R1 of a fusion between the growth rate-regulated rRNA
      promoter rrnBP1 and a gfp gene encoding an unstable variant of the green
      fluorescent protein made it possible to monitor the physiological activity of P.
      putida R1 cells at different positions in the biofilms. Combining this with
      fluorescent in situ hybridization and scanning confocal laser microscopy showed
      that the two organisms compete or display commensal interactions depending on
      their relative physical positioning in the biofilm. In the initial phase of
      biofilm development, the growth activity of P. putida R1 was shown to be higher
      near microcolonies of Acinetobacter strain C6. High-pressure liquid
      chromatography analysis showed that in the effluent of the Acinetobacter strain
      C6 monoculture biofilm the metabolic intermediate benzoate accumulated, whereas
      in the biculture biofilms this was not the case, suggesting that in these
      biofilms the excess benzoate produced by Acinetobacter strain C6 leaks into the
      surrounding environment, from where it is metabolized by P. putida R1. After a
      few days, Acinetobacter strain C6 colonies were overgrown by P. putida R1 cells
      and new structures developed, in which microcolonies of Acinetobacter strain C6
      cells were established in the upper layer of the biofilm. In this way the two
      organisms developed structural relationships allowing Acinetobacter strain C6 to
      be close to the bulk liquid with high concentrations of benzyl alcohol and
      allowing P. putida R1 to benefit from the benzoate leaking from Acinetobacter
      strain C6. We conclude that in chemostats, where the organisms cannot establish
      in fixed positions, the two strains will compete for the primary carbon source,
      benzyl alcohol, which apparently gives Acinetobacter strain C6 a growth
      advantage, probably because it converts benzyl alcohol to benzoate with a higher
      yield per time unit than P. putida R1. In biofilms, however, the organisms
      establish structured, surface-attached consortia, in which heterogeneous
      ecological niches develop, and under these conditions competition for the primary
      carbon source is not the only determinant of biomass and population structure.

PMID- 11976127
TI  - Use of recombinant cellulose-binding domains of Trichoderma reesei cellulase as a
      selective immunocytochemical marker for cellulose in protozoa.
AB  - Some unicellular organisms are able to encyst as a protective response to a
      harmful environment. The cyst wall usually contains chitin as its main structural
      constituent, but in some cases, as in Acanthamoeba, it consists of cellulose
      instead. Specific cytochemical differentiation between cellulose and chitin by
      microscopy has not been possible, due to the similarity of their constituent beta
      1,4-linked hexose backbones. Thus, various fluorescent brightening agents and
      lectins bind to both cellulose and chitin. We have used a recombinant cellulose
      binding protein consisting of two cellulose-binding domains (CBDs) from
      Trichoderma reesei cellulases linked together in combination with monoclonal
      anticellulase antibodies and anti-mouse immunoglobulin fluorescein conjugate to
      specifically stain cellulose in the cysts of Acanthamoeba strains for
      fluorescence microscopy imaging. Staining was observed in ruptured cysts and
      frozen sections of cysts but not in intact mature cysts. No staining reaction was
      observed with the chitin-containing cyst walls of Giardia intestinalis, Entamoeba
      dispar, or Pneumocystis carinii. Thus, the recombinant CBD can be used as a
      marker to distinguish between cellulose and chitin. Thirteen of 25 environmental
      or clinical isolates of amoebae reacted in the CBD binding assay. All 13 isolates
      were identified as Acanthamoeba spp. Five isolates of Hartmannella and seven
      isolates of Naegleria tested negative in the CBD binding assay. Whether cyst wall
      cellulose really is a unique property of Acanthamoeba spp. among free-living
      amoebae, as suggested by our findings, remains to be shown in more extensive
      studies.

PMID- 11976128
TI  - Assessing the role of Pseudomonas aeruginosa surface-active gene expression in
      hexadecane biodegradation in sand.
AB  - Low pollutant substrate bioavailability limits hydrocarbon biodegradation in
      soils. Bacterially produced surface-active compounds, such as rhamnolipid
      biosurfactant and the PA bioemulsifying protein produced by Pseudomonas
      aeruginosa, can improve bioavailability and biodegradation in liquid culture, but
      their production and roles in soils are unknown. In this study, we asked if the
      genes for surface-active compounds are expressed in unsaturated porous media
      contaminated with hexadecane. Furthermore, if expression does occur, is
      biodegradation enhanced? To detect expression of genes for surface-active
      compounds, we fused the gfp reporter gene either to the promoter region of pra,
      which encodes for the emulsifying PA protein, or to the promoter of the
      transcriptional activator rhlR. We assessed green fluorescent protein (GFP)
      production conferred by these gene fusions in P. aeruginosa PG201. GFP was
      produced in sand culture, indicating that the rhlR and pra genes are both
      transcribed in unsaturated porous media. Confocal laser scanning microscopy of
      liquid drops revealed that gfp expression was localized at the hexadecane-water
      interface. Wild-type PG201 and its mutants that are deficient in either PA
      protein, rhamnolipid synthesis, or both were studied to determine if the genetic
      potential to make surface-active compounds confers an advantage to P. aeruginosa
      biodegrading hexadecane in sand. Hexadecane depletion rates and carbon
      utilization efficiency in sand culture were the same for wild-type and mutant
      strains, i.e., whether PG201 was proficient or deficient in surfactant or
      emulsifier production. Environmental scanning electron microscopy revealed that
      colonization of sand grains was sparse, with cells in small monolayer clusters
      instead of multilayered biofilms. Our findings suggest that P. aeruginosa likely
      produces surface-active compounds in sand culture. However, the ability to
      produce surface-active compounds did not enhance biodegradation in sand culture
      because well-distributed cells and well-distributed hexadecane favored direct
      contact to hexadecane for most cells. In contrast, surface-active compounds
      enable bacteria in liquid culture to adhere to the hexadecane-water interface
      when they otherwise would not, and thus production of surface-active compounds is
      an advantage for hexadecane biodegradation in well-dispersed liquid systems.

PMID- 11976129
TI  - Alterations in Vibrio fischeri motility correlate with a delay in symbiosis
      initiation and are associated with additional symbiotic colonization defects.
AB  - Motility is required for Vibrio fischeri cells to interact with and specifically
      colonize the light-emitting organ of their host, the squid Euprymna scolopes. To
      investigate the influence of motility on the expression of the symbiotic
      phenotype, we isolated mutants of the squid symbiont V. fischeri ES114 that had
      altered migration abilities. Spontaneous hyperswimmer (HS) mutants, which
      migrated more rapidly in soft agar and were hyperflagellated relative to the wild
      type, were isolated and grouped into three phenotypic classes. All of the HS
      strains tested, regardless of class, were delayed in symbiosis initiation. This
      result suggested that the hypermotile phenotype alone contributes to an inability
      to colonize squid normally. Class III HS strains showed the greatest colonization
      defect: they colonized squid to a level that was only 0.1 to 10% that achieved by
      ES114. In addition, class III strains were defective in two capabilities,
      hemagglutination and luminescence, that have been previously described as
      colonization factors in V. fischeri. Class II and III mutants also share a mucoid
      colony morphology; however, class II mutants can colonize E. scolopes to a level
      that was 40% of that achieved by ES114. Thus, the mucoid phenotype alone does not
      contribute to the greater defect exhibited by class III strains. When squid were
      exposed to ES114 and any one of the HS mutant strains as a coinoculation, the
      parent strain dominated the resulting symbiotic light-organ population. To
      further investigate the colonization defects of the HS strains, we used confocal
      laser-scanning microscopy to visualize V. fischeri cells in their initial
      interaction with E. scolopes tissue. Compared to ES114, HS strains from all three
      classes were delayed in two behaviors involved in colonization: (i) aggregation
      on host-derived mucus structures and (ii) migration to the crypts. These results
      suggest that, while motility is required to initiate colonization, the presence
      of multiple flagella may actually interfere with normal aggregation and
      attachment behavior. Furthermore, the pleiotropic nature of class III HS strains
      provides evidence that motility is coregulated with other symbiotic determinants
      in V. fischeri.

PMID- 11976130
TI  - Double-stranded RNA mycovirus from Fusarium graminearum.
AB  - Double-stranded RNA (dsRNA) viruses in some fungi are associated with
      hypovirulence and have been used or proposed as biological control agents. We
      isolated 7.5-kb dsRNAs from 13 of 286 field strains of Fusarium graminearum
      isolated from maize in Korea. One of these strains, DK21, was examined in more
      detail. This strain had pronounced morphological changes, including reduction in
      mycelial growth, increased pigmentation, reduced virulence towards wheat, and
      decreased (60-fold) production of trichothecene mycotoxins. The presence or
      absence of the 7.5-kb dsRNA was correlated with the changes in pathogenicity and
      morphology. The dsRNA could be transferred to virus-free strains by hyphal
      fusion, and the recipient strain acquired the virus-associated phenotype of the
      donor strain. The dsRNA was transmitted to approximately 50% of the conidia, and
      only colonies resulting from conidia carrying the mycovirus had the virus
      associated phenotype. Partial nucleotide sequences of the purified dsRNA identify
      an RNA-dependent RNA polymerase sequence and an ATP-dependent helicase that are
      closely related to those of Cryphonectria hypovirus and Barley yellow mosaic
      virus. Collectively, these results suggest that this dsRNA isolated from F.
      graminearum encodes traits for hypovirulence.

PMID- 11976132
TI  - Rapid immunoassays for detection of UV-induced cyclobutane pyrimidine dimers in
      whole bacterial cells.
AB  - Immunoassays were developed to measure DNA damage retained by UV-irradiated whole
      bacterial cells. Active Mycobacterium parafortuitum and Serratia marcescens cells
      were fixed and incubated with cyclobutane pyrimidine dimer-binding antibodies
      after being exposed to known UV doses (254 nm). When both fluorescent (Alexa
      Fluor 488) and radiolabeled ((125)I) secondary antibodies were used as reporters,
      indirect whole-cell assays were sensitive enough to measure intracellular UV
      photoproducts in M. parafortuitum and S. marcescens cells as well as
      photoenzymatic repair responses in S. marcescens cells. For the same UV dose,
      fluorescent DNA photoproduct detection limits in whole-cell assays
      (immunofluorescent microscopy) were similar to those in fluorescent assays
      performed on membrane-bound DNA extracts (immunoslot blot). With either
      fluorescent or radiolabeled reporters, the intracellular cyclobutane pyrimidine
      dimer content of UV-irradiated whole bacterial cells could be reliably quantified
      after undergoing a <0.5-order-of-magnitude decrease in culturability.
      Immunofluorescent microscopy results showed that photoenzymatic repair competence
      is not uniformly distributed among exponential-growth UV-irradiated pure
      cultures.

PMID- 11976131
TI  - High-density microarray of small-subunit ribosomal DNA probes.
AB  - Ribosomal DNA sequence analysis, originally conceived as a way to provide a
      universal phylogeny for life forms, has proven useful in many areas of biological
      research. Some of the most promising applications of this approach are presently
      limited by the rate at which sequences can be analyzed. As a step toward
      overcoming this limitation, we have investigated the use of photolithography chip
      technology to perform sequence analyses on amplified small-subunit rRNA genes.
      The GeneChip (Affymetrix Corporation) contained 31,179 20-mer oligonucleotides
      that were complementary to a subalignment of sequences in the Ribosomal Database
      Project (RDP) (B. L. Maidak et al., Nucleic Acids Res. 29:173-174, 2001). The
      chip and standard Affymetrix software were able to correctly match small-subunit
      ribosomal DNA amplicons with the corresponding sequences in the RDP database for
      15 of 17 bacterial species grown in pure culture. When bacteria collected from an
      air sample were tested, the method compared favorably with cloning and sequencing
      amplicons in determining the presence of phylogenetic groups. However, the method
      could not resolve the individual sequences comprising a complex mixed sample.
      Given these results and the potential for future enhancement of this technology,
      it may become widely useful.

PMID- 11976134
TI  - Conservation of plasmid-encoded traits among bean-nodulating Rhizobium species.
AB  - Rhizobium etli type strain CFN42 contains six plasmids. We analyzed the
      distribution of genetic markers from some of these plasmids in bean-nodulating
      strains belonging to different species (Rhizobium etli, Rhizobium gallicum,
      Rhizobium giardinii, Rhizobium leguminosarum, and Sinorhizobium fredii). Our
      results indicate that independent of geographic origin, R. etli strains usually
      share not only the pSym plasmid but also other plasmids containing symbiosis
      related genes, with a similar organization. In contrast, strains belonging to
      other bean-nodulating species seem to have acquired only the pSym plasmid from R.
      etli.

PMID- 11976133
TI  - Biochemical and genetic characterization of the two-peptide bacteriocin enterocin
      1071 produced by Enterococcus faecalis FAIR-E 309.
AB  - The structural genes for the two-peptide bacteriocin enterocin 1071 (Ent1071) in
      Enterococcus faecalis FAIR-E 309 were cloned. DNA sequence analysis showed that
      the enterocin 1071A (Ent1071A) peptide of strain FAIR-E 309 differed by two amino
      acids from the Ent1071A reported for E. faecalis BFE 1071 (E. Balla, L. M. T.
      Dicks, M. Du Toit, M. J. van der Merwe, and W. H. Holzapfel, Appl. Environ.
      Microbiol. 66:1298-1304, 2000), while the Ent1071B gene encoded identical
      peptides in these strains. However, resequencing of ent1071A from E. faecalis BFE
      1071 showed that the Ent1071A peptide sequence reported previously was incorrect
      in two amino acids. Also, ent1071B in E. faecalis FAIR-E 309 encoded a prepeptide
      that was three amino acids shorter than that previously reported for E. faecalis
      BFE 1071 Ent1071B. A presumptive immunity gene (eni1071) was located downstream
      of the bacteriocin structural genes. This gene was cloned into the heterologous
      host E. faecalis ATCC 19433 and was shown to confer immunity. A truncated ABC
      transporter gene was located upstream of the Ent1071 structural genes.

PMID- 11976135
TI  - Engineered rhizosphere: the trophic bias generated by opine-producing plants is
      independent of the opine type, the soil origin, and the plant species.
AB  - In a previous study, we demonstrated that transgenic Lotus plants producing
      opines (which are small amino acid and sugar conjugates) specifically favor
      growth of opine-degrading rhizobacteria. The opine-induced bias was repeated and
      demonstrated with another soil type and another plant species (Solanum nigrum).
      This phenomenon is therefore independent of both soil type and plant species.

PMID- 11976136
TI  - Genetic characterization of Cylindrospermopsis raciborskii (cyanobacteria)
      isolates from diverse geographic origins based on nifH and cpcBA-IGS nucleotide
      sequence analysis.
AB  - Isolates of the toxic, N(2)-fixing species Cylindrospermopsis raciborskii from
      various geographic locations were analyzed with respect to their genetic
      diversity based on the nifH and cpcBA-IGS genes. Gene sequences clustered
      according to their geographic origin, with the nifH sequences separating into
      European, Australian, and American groups and the cpcBA-IGS sequences separating
      into American and European or Australian groups. PCR primers for both genes were
      designed to exclusively amplify DNA from Cylindrospermopsis species, and an
      additional primer set for cpcBA-IGS was designed to specifically amplify the
      American C. raciborskii strains.

PMID- 11976137
TI  - Molecular characterization of the leucine cluster in Buchnera sp. strain PSY, a
      primary endosymbiont of the aphid Pemphigus spyrothecae.
AB  - Buchnera strains from most aphid subfamilies studied to date have been found to
      carry the leucine gene cluster (leuA, -B, -C, and -D) on a plasmid, an
      organization unique among bacteria. Here, however, we demonstrate a classical
      chromosomal location of the cluster in Buchnera sp. strain PSY from the aphid
      Pemphigus spyrothecae (subfamily Pemphiginae). The genes that flank leuABCD in
      Buchnera sp. strain PSY appear to be adjacent in the genome of Buchnera sp.
      strain APS, a strain carrying a leucine plasmid. We propose that the presence of
      a leucine plasmid predates the diversification of symbiotic Buchnera and that the
      chromosomal location observed in Buchnera sp. strain PSY arose by a transfer of
      the leucine genes from a plasmid to the chromosome.

PMID- 11976138
TI  - Efficacy of common laboratory disinfectants on the infectivity of Cryptosporidium
      parvum oocysts in cell culture.
AB  - Nine liquid disinfectants were tested for their ability to reduce infectivity of
      Cryptosporidium parvum oocysts in cell culture. A 4-min exposure to 6% hydrogen
      peroxide and a 13-min exposure to ammonium hydroxide-amended windshield washer
      fluid reduced infectivity 1,000-fold. Other disinfectants tested (70% ethanol,
      37% methanol, 6% sodium hypochlorite, 70% isopropanol, and three commercial
      disinfectants) did not reduce the infectivity after a 33-min exposure. The
      results indicate that hydrogen peroxide and windshield washer fluid or ammonium
      hydroxide disinfectant may be suitable laboratory disinfectants against C. parvum
      oocysts.

PMID- 11976139
TI  - Rapid detection of Shigella species in environmental sewage by an immunocapture
      PCR with universal primers.
AB  - In the present study, we developed a quick, highly specific method for detection
      of Shigella species by combining immunocapturing of the bacteria and a universal
      primer PCR. The method drastically enhances test sensitivity, and it can be used
      not only for identification of Shigella species in the environment but also for
      rapid detection of other pathogens.

PMID- 11976140
TI  - Biotransformation of 2,7-dichloro- and 1,2,3,4-tetrachlorodibenzo-p-dioxin by
      Sphingomonas wittichii RW1.
AB  - Aerobic biotransformation of the diaryl ethers 2,7-dichlorodibenzo-p-dioxin and
      1,2,3,4-tetrachlorodibenzo-p-dioxin by the dibenzo-p-dioxin-utilizing strain
      Sphingomonas wittichii RW1, producing corresponding metabolites, was demonstrated
      for the first time. Our strain transformed 2,7-dichlorodibenzo-p-dioxin, yielding
      4-chlorocatechol, and 1,2,3,4-tetrachlorodibenzo-p-dioxin, producing 3,4,5,6
      tetrachlorocatechol and 2-methoxy-3,4,5,6-tetrachlorophenol; all of these
      compounds were unequivocally identified by mass spectrometry both before and
      after N,O-bis(trimethylsilyl)-trifluoroacetamide derivatization by comparison
      with authentic standards. Additional experiments showed that strain RW1 formed a
      second metabolite, 2-methoxy-3,4,5,6-tetrachlorophenol, from the original
      degradation product, 3,4,5,6-tetrachlorocatechol, by methylation of one of the
      two hydroxy substituents.

PMID- 11976141
TI  - Genomic sequence and evolution of marine cyanophage P60: a new insight on lytic
      and lysogenic phages.
AB  - The genome of cyanophage P60, a lytic virus which infects marine Synechococcus
      WH7803, was completely sequenced. The P60 genome contained 47,872 bp with 80
      potential open reading frames that were mostly similar to the genes found in
      lytic phages like T7, phi-YeO3-12, and SIO1. The DNA replication system,
      consisting of primase-helicase and DNA polymerase, appeared to be more conserved
      in podoviruses than in siphoviruses and myoviruses, suggesting that DNA
      replication genes could be the critical elements for lytic phages. Strikingly
      high sequence similarities in the regions coding for nucleotide metabolism were
      found between cyanophage P60 and marine unicellular cyanobacteria.

PMID- 11976142
TI  - Prevalence of Enterocytozoon bieneusi in swine: an 18-month survey at a
      slaughterhouse in Massachusetts.
AB  - Slaughterhouse pig samples were analyzed by PCR for Enterocytozoon bieneusi
      infection. Thirty-two percent were found to be positive, with rates being higher
      over the summer months. Three isolates from pigs were identical in their
      ribosomal internal transcribed spacer sequence to human E. bieneusi type D, two
      were identical to type F (from a pig), and nine were previously unreported. The
      viability of these spores was demonstrated by their ability to infect gnotobiotic
      piglets. The presence of the infection in liver was shown by in situ
      hybridization.

PMID- 11976143
TI  - Role of glucose in enhancing the temperature-dependent growth inhibition of
      Escherichia coli O157:H7 ATCC 43895 by a Pseudomonas sp.
AB  - Growth of Escherichia coli O157:H7 strain ATCC 43895 was monitored at 5, 10, 15,
      and 25 degrees C in both pure and mixed (1:1) cultures with a gluconate-producing
      Pseudomonas sp. found in meat to evaluate the effect of the absence and presence
      of 1% glucose in broth on temperature-dependent competition. The number of
      colonies of the Pseudomonas strain exceeded 9 log CFU/ml under all conditions
      tested. The pathogen grew better as the temperature increased from 10 to 15 and
      25 degrees C and grew better in pure culture than in mixed cultures. Pseudomonas
      sp. inhibited E. coli O157:H7 in cocultures with glucose at 10 degrees C, while
      at 15 degrees C the pathogen exhibited a biphasic pattern of growth with an
      intermediate inactivation period. Pathogen inhibition was much weaker in
      cocultures grown without glucose at 10 to 15 degrees C and, irrespective of
      glucose, at 25 degrees C. These results indicate that glucose enhances the growth
      inhibition of E. coli O157:H7 by some Pseudomonas spp., potentially due to its
      rapid uptake and conversion to gluconate, at low (< or = 15 degrees C)
      temperatures.

PMID- 11976144
TI  - Fate of Escherichia coli O157:H7 in manure-amended soil.
AB  - Escherichia coli O157:H7 cells survived for up to 77, >226, and 231 days in
      manure-amended autoclaved soil held at 5, 15, and 21 degrees C, respectively.
      Pathogen populations declined more rapidly in manure-amended unautoclaved soil
      under the same conditions, likely due to antagonistic interactions with
      indigenous soil microorganisms. E. coli O157:H7 cells were inactivated more
      rapidly in both autoclaved and unautoclaved soils amended with manure at a ratio
      of 1 part manure to 10 parts soil at 15 and 21 degrees C than in soil samples
      containing dilute amounts of manure. The manure-to-soil ratio, soil temperature,
      and indigenous microorganisms of the soil appear to be contributory factors to
      the pathogen's survival in manure-amended soil.

PMID- 11976145
TI  - Thermodynamic analysis of growth temperature dependence in the adhesion of
      Candida parapsilosis to polystyrene.
AB  - The purpose of this work was to study the adhesion to polystyrene of two Candida
      parapsilosis strains, grown at 22 and 37 degrees C, in terms of hydrophobicity,
      surface charge, and interaction free energy. Growth temperature changed the
      surface properties of microorganisms, yielding a good correlation between
      thermodynamic predictions and adhesion behavior.

PMID- 11976146
TI  - Formation of protoplasts from cultured tobacco cells and Arabidopsis thaliana by
      the action of cellulosomes and pectate lyase from Clostridium cellulovorans.
AB  - The crude culture supernatants from Clostridium cellulovorans were tested for
      their ability to convert plant cells to protoplasts. The supernatants readily
      released protoplasts from cultured tobacco cells and Arabidopsis thaliana. The
      crude culture supernatant from pectin-grown cells was more active than
      supernatants from glucose-, cellobiose-, xylan-, and locust bean gum-grown cells.
      After removal of cellulosomes, the crude culture supernatant lost its protoplast
      formation activity. The protoplast formation activity of the crude culture
      supernatant from C. cellulovorans was more effective than those of commercial
      enzymes based on protein content.

PMID- 11976147
TI  - Cloning of Escherichia coli lacZ and lacY genes and their expression in
      Gluconobacter oxydans and Acetobacter liquefaciens.
AB  - An efficient transformation protocol for Gluconobacter oxydans and Acetobacter
      liquefaciens strains was developed by preparation of electrocompetent cells grown
      on yeast extract-ethanol medium. Plasmid pBBR122 was used as broad-host-range
      vector to clone the Escherichia coli lacZY genes in G. oxydans and A.
      liquefaciens. Although both lac genes were functionally expressed in both acetic
      acid bacteria, only a few transformants were able to grow on lactose. However,
      this ability strictly depended on the presence of a plasmid expressing both lac
      genes. Mutations in the plasmids and/or in the chromosome were excluded as the
      cause of growth ability on lactose.

PMID- 11976148
TI  - Construction and application of epitope- and green fluorescent protein-tagging
      integration vectors for Bacillus subtilis.
AB  - Here we describe the construction and application of six new tagging vectors
      allowing the fusion of two different types of tagging sequences, epitope and
      localization tags, to any Bacillus subtilis protein. These vectors are based on
      the backbone of pMUTIN2 and replace the lacZ gene with tagging sequences. Fusion
      of the tagging sequences occurs by PCR amplification of the 3' terminal part of
      the gene of interest (about 300 bp), insertion into the tagging vector in such a
      way that a fusion protein will be synthesized upon integration of the whole
      vector via homologous recombination with the chromosomal gene. Three of these
      tagging sequences (FLAG, hemagglutinin, and c-Myc) allow the covalent addition of
      a short epitope tag and thereby detection of the fusion proteins in immunoblots,
      while three other tags (green fluorescent protein(+), yellow fluorescent protein,
      and cyan fluorescent protein) are helpful in assigning proteins within one of the
      compartments of the cell. The versatility of these vectors was demonstrated by
      fusing these tags to the cytoplasmically located HtpG and the inner membrane
      protein FtsH.

PMID- 11976149
TI  - Hemoglobin in Frankia, a nitrogen-fixing actinomycete.
AB  - Frankia strain CcI3 grown in culture produced a hemoglobin which had optical
      absorption bands typical of a hemoglobin and a molecular mass of 14.1 kDa. Its
      equilibrium oxygen binding constant was 274 nM, the oxygen dissociation rate
      constant was 56 s(-1), and the oxygen association rate constant was 206 microM(
      1) s(-1).

PMID- 11976150
TI  - Homocysteine, B vitamins, and cognitive deficit in the elderly.

PMID- 11976151
TI  - How adaptable is the intestine in patients with short-bowel syndrome?

PMID- 11976152
TI  - Protective nutrients and functional foods for the gastrointestinal tract.
AB  - Epithelial and other cells of the gastrointestinal mucosa rely on both luminal
      and bloodstream sources for their nutrition. The term functional food is used to
      describe nutrients that have an effect on physiologic processes that is separate
      from their established nutritional function, and some of these nutrients are
      proposed to promote gastrointestinal mucosal integrity. We review the recent in
      vitro, animal, and clinical experiments that evaluated the role of several types
      of gastrointestinal functional foods, including the amino acids glutamine and
      arginine, the essential micronutrients vitamin A and zinc, and 2 classes of food
      additives, prebiotics and probiotics. Many of the data from preclinical studies
      support a strong role for enteral nutrients in gastrointestinal health; in
      comparison, the data from human studies are limited. In some cases, impressive
      data from in vitro and animal studies have not been replicated in human trials.
      Other clinical trials have shown positive health benefits, but some of those
      studies were plagued by flaws in study design or analysis. The methods available
      to detect important changes in human gastrointestinal function and structure are
      still limited, but with the development of more sensitive measures of
      gastrointestinal function, the effects of specific nutrients may be more easily
      detected. This may facilitate the development of phase 3 clinical trials designed
      to more rigorously evaluate the effects of a particular nutrient by focusing on
      valid and reliable outcome measures. Regulatory changes in the way in which
      health claims can be made for dietary supplements should also be encouraged.

PMID- 11976153
TI  - Associations of body mass index and obesity with physical activity, food choices,
      alcohol intake, and smoking in the 1982-1997 FINRISK Studies.
AB  - BACKGROUND: Recent increases in the prevalence of obesity worldwide are suggested
      to be caused largely by an environment that promotes sedentariness and excessive
      food intake. OBJECTIVE: We investigated associations of body mass index (BMI) and
      obesity with physical activity, food choices, alcohol consumption, and smoking
      history. In addition, we examined the consistency of these associations over
      time, with the aim of assessing whether the significance of lifestyle variables
      as correlates of obesity increased over a 15-y period. DESIGN: Independent cross
      sectional surveys were carried out in 1982, 1987, 1992, and 1997. Altogether,
      24604 randomly selected men and women (aged 25-64 y) participated in these
      surveys. The subjects' weights and heights were measured, and data on lifestyle
      were collected with self-administered questionnaires. RESULTS: In men and women,
      perceived general health, leisure-time physical activity, and daily vegetable
      consumption were inversely associated with obesity, as were bread consumption in
      women and activity at work in men. Consumption of sausages, milk, and sour milk
      and heavy work (in women only) were positively associated with obesity. Obesity
      was also associated with alcohol consumption and smoking history. Most
      associations were constant over the 15-y period. However, the inverse
      associations of BMI with physical activity in women and with perceived health in
      men seemed to strengthen over time. CONCLUSIONS: A physically active lifestyle
      with abstention from smoking, moderate alcohol consumption, and consumption of
      healthy foods maximizes the chances of having a normal weight. The significance
      of avoiding sedentariness increases over time as a factor associated with normal
      weight.

PMID- 11976154
TI  - Effects of exercise intensity on cardiovascular fitness, total body composition,
      and visceral adiposity of obese adolescents.
AB  - BACKGROUND: Little is known about how the intensity of exercise influences
      cardiovascular fitness and body composition, especially in obese adolescents.
      OBJECTIVE: Our goal was to determine the effects of physical training intensity
      on the cardiovascular fitness, percentage of body fat (%BF), and visceral adipose
      tissue (VAT) of obese adolescents. DESIGN: Obese 13-16-y-olds (n = 80) were
      assigned to 1) biweekly lifestyle education (LSE), 2) LSE + moderate-intensity
      physical training, or 3) LSE + high-intensity physical training. The intervention
      lasted 8 mo. Physical training was offered 5 d/wk, and the target energy
      expenditure for all subjects in physical training groups was 1047 kJ (250
      kcal)/session. Cardiovascular fitness was measured with a multistage treadmill
      test, %BF with dual-energy X-ray absorptiometry, and VAT with magnetic resonance
      imaging. RESULTS: The increase in cardiovascular fitness in the high-intensity
      physical training group, but not in the moderate-intensity group, was
      significantly greater than that in the LSE alone group (P = 0.009); no other
      comparisons of the 3 groups were significant. Compared with the LSE alone group,
      a group composed of subjects in both physical training groups combined who
      attended training sessions >or=2 d/wk showed favorable changes in cardiovascular
      fitness (P < 0.001), %BF (P = 0.001), and VAT (P = 0.029). We found no evidence
      that the high-intensity physical training was more effective than the moderate
      intensity physical training in enhancing body composition. CONCLUSIONS: The
      cardiovascular fitness of obese adolescents was significantly improved by
      physical training, especially high-intensity physical training. The physical
      training also reduced both visceral and total-body adiposity, but there was no
      clear effect of the intensity of physical training.

PMID- 11976155
TI  - Differences in the relation of obesity to serum triacylglycerol and VLDL subclass
      concentrations between black and white children: the Bogalusa Heart Study.
AB  - BACKGROUND: Obese children and adults, particularly those with abdominal obesity,
      have an elevated serum triacylglycerol concentration. Furthermore,
      triacylglycerol concentrations are generally higher in whites than in blacks, and
      the relation of obesity to triacylglycerol concentrations may be stronger in
      whites. However, there is little information on the relation of obesity to the
      metabolically distinct subclasses of VLDL in children. OBJECTIVE: The objective
      was to examine possible differences between blacks (n = 367) and whites (n = 549)
      in mean concentrations of triacylglycerols, in mean concentrations of small and
      large VLDL, and in the relation of waist circumference to concentrations of
      triacylglycerol and VLDL subclasses. DESIGN: We measured VLDL subclass
      concentrations and assessed the relation of various obesity indexes to
      triacylglycerols in a cross-sectional study of 10- to 17-y-olds. RESULTS: The
      mean triacylglycerol concentration was 0.3 mmol/L (25 mg/dL) higher in white than
      in black children, primarily because of a 0.2-mmol/L (140%) difference in mean
      concentrations of large VLDL. In contrast, the mean concentrations of small VLDL
      differed by only 0.05 mmol/L (29%). In addition, the relations of waist girth to
      concentrations of triacylglycerol and large VLDL were 2- to 6-fold stronger among
      white children than among black children. Although white children had higher
      concentrations of large VLDL than did black children, this difference increased
      from 0.1 to 0.4 mmol/L across quintiles of waist circumference. Waist
      circumference was not significantly related to concentrations of small VLDL.
      CONCLUSION: These contrasting associations with obesity, which differ between
      white and black children, suggest that information on VLDL subclasses could
      provide additional information on the risk of obesity-related ischemic heart
      disease.

PMID- 11976156
TI  - Soluble fiber intake at a dose approved by the US Food and Drug Administration
      for a claim of health benefits: serum lipid risk factors for cardiovascular
      disease assessed in a randomized controlled crossover trial.
AB  - BACKGROUND: The US Food and Drug Administration (FDA) approved health claims for
      2 dietary fibers, beta-glucan (0.75 g/serving) and psyllium (1.78 g/serving), on
      the assumption that 4 servings/d would reduce cardiovascular disease risk.
      OBJECTIVE: We assessed the efficacy of this dose of fibers in reducing serum
      lipid risk factors for cardiovascular disease. DESIGN: Sixty-eight hyperlipidemic
      adults consumed a test (high-fiber) and a control low-fat (25% of energy), low
      cholesterol (<150 mg/d) diet for 1 mo each in a randomized crossover study. The
      high-fiber diet included 4 servings/d of foods containing beta-glucan or psyllium
      that delivered 8 g/d more soluble fiber than did similar, unsupplemented foods in
      the control diet. Fasting blood samples and blood pressure readings were obtained
      at baseline and weeks 2 and 4, and the subjects' weight was monitored weekly.
      RESULTS: Compared with the control diet, the high-fiber diet reduced total
      cholesterol (2.1 +/- 0.7%; P = 0.003), total:HDL cholesterol (2.9 +/- 0.8%; P =
      0.001), LDL:HDL cholesterol (2.4 +/- 1.0%; P = 0.015), and apolipoprotein B:A-I
      (1.4 +/- 0.8%; P = 0.076). Applying the Framingham cardiovascular disease risk
      equation to the data confirmed a reduction in risk of 4.2 +/- 1.4% (P = 0.003).
      Small reductions in blood pressure were found after both diets. The subjects
      reported no significant differences in palatability or gastrointestinal symptoms
      between the diets. CONCLUSIONS: The reduction in serum lipid risk factors for
      cardiovascular disease supports the FDA's approval of a health claim for a
      dietary fiber intake of 4 servings/d. Although relatively small in terms of
      patient treatment, the reduction in cardiovascular disease risk is likely to be
      significant on a population basis.

PMID- 11976157
TI  - Composition (lean and fat tissue) of weight changes in adult Danes.
AB  - BACKGROUND: Weight loss may be associated with unfavorable changes in body
      composition not compensated for by subsequent weight gain. OBJECTIVE: We examined
      the composition of weight change in relation to obesity, previous weight changes,
      weight-loss attempts, and physical activity. DESIGN: Part of the Danish MONICA
      (Monitoring Trends in Cardiovascular Disease) project, this was a longitudinal
      population study of changes in weight and body composition, with examinations in
      1982-1983, 1987-1988, and 1993-1994. A total of 1236 men and 1200 women aged 35,
      45, 55, or 65 y in 1987-1988 participated. Changes in fat and fat-free mass were
      measured by bioelectrical impedance. RESULTS: Before adjustment for age-related
      changes, fat-free mass made up 41% of weight lost and 24% of weight gained in
      men. In women, loss of fat-free mass (35%) was more than double that of gains
      (15%). After adjustment, the fractions of weight gained as fat-free mass were not
      significantly different from the fractions lost. These fractions were independent
      of age, obesity, and weight changes in the previous 5 y; successful weight-loss
      attempts; and physical activity. Independent of age and degree of obesity, weight
      changes were associated with greater changes in fat-free mass in men than in
      women. CONCLUSIONS: These data do not support the theory that weight loss or
      weight cycling may lead to an unfavorable body composition, nor do they provide a
      biological explanation for why long-term weight loss is often unsuccessful.
      However, the metabolic and health consequences of weight change may differ in men
      and women.

PMID- 11976158
TI  - Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic
      adults.
AB  - BACKGROUND: Epidemiologic studies have found whole-grain intake to be inversely
      associated with the risk of type 2 diabetes and heart disease. OBJECTIVE: We
      tested the hypothesis that whole-grain consumption improves insulin sensitivity
      in overweight and obese adults. DESIGN: This controlled experiment compared
      insulin sensitivity between diets (55% carbohydrate, 30% fat) including 6-10
      servings/d of breakfast cereal, bread, rice, pasta, muffins, cookies, and snacks
      of either whole or refined grains. Total energy needs were estimated to maintain
      body weight. Eleven overweight or obese [body mass index (in kg/m(2)): 27-36]
      hyperinsulinemic adults aged 25-56 y participated in a randomized crossover
      design. At the end of each 6-wk diet period, the subjects consumed 355 mL (12 oz)
      of a liquid mixed meal, and blood samples were taken over 2 h. The next day a
      euglycemic hyperinsulinemic clamp test was administered. RESULTS: Fasting insulin
      was 10% lower during consumption of the whole-grain than during consumption of
      the refined-grain diet (mean difference: -15 +/- 5.5 pmol/L; P = 0.03). After the
      whole-grain diet, the area under the 2-h insulin curve tended to be lower (-8832
      pmol.min/L; 95% CI: -18720, 1062) than after the refined-grain diet. The rate of
      glucose infusion during the final 30 min of the clamp test was higher after the
      whole-grain diet (0.07 x 10(-4) mmol.kg(-1).min(-1) per pmol/L; 95% CI: 0.003 x
      10(-4), 0.144 x 10(-4)). CONCLUSION: Insulin sensitivity may be an important
      mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart
      disease.

PMID- 11976160
TI  - Age, sex, ethnicity, body composition, and resting energy expenditure of obese
      African American and white children and adolescents.
AB  - BACKGROUND: African Americans may have a lower resting energy expenditure (REE)
      than do whites, although the data are limited for obese children and adolescents
      and for boys. Differences in bone density and trunk lean body mass may account
      for some of these measured differences in REE. OBJECTIVE: We assessed the REE and
      body composition of obese African American and white children and adolescents.
      DESIGN: Obese, 5-17-y-old children and adolescents were evaluated (n = 203). Body
      composition was assessed by dual-energy X-ray absorptiometry. REE was measured by
      open-circuit calorimetry. African American and white children were compared. The
      relation between REE and the independent variables (age, sex, ethnic group, fat
      mass, and fat-free mass or lean tissue mass) was assessed. RESULTS: Of those
      evaluated, 66% were girls and 34% were African American. Age, sex, pubertal
      status, and body composition did not differ significantly by ethnic group. All
      the independent variables were significantly associated with REE. Using lean
      tissue mass to account for differences in bone density did not significantly
      alter the results. REE decreased with age and was lower in the girls than in the
      boys and in the African Americans than in the whites. When trunk fat-free mass
      was included in the model in place of whole-body fat-free mass, the ethnic
      difference in REE decreased. CONCLUSIONS: Adjustment for trunk lean tissue mass
      partially explains the lower REE of obese African American children and
      adolescents. The lower relative REE of older obese children suggests the
      importance of early intervention in the prevention of childhood obesity. The
      lower REE of girls and of African Americans may contribute to the difficulty in
      weight management in these groups.

PMID- 11976159
TI  - Effects of wine intake on postprandial plasma amino acid and protein kinetics in
      type 1 diabetes.
AB  - BACKGROUND: Alcohol may impair protein turnover and insulin sensitivity in vivo.
      OBJECTIVE: The acute effects of moderate wine intake on amino acid kinetics and
      on the fractional synthetic rate (FSR) of albumin and fibrinogen in patients with
      type 1 diabetes were studied. DESIGN: Six patients with type 1 diabetes ingested
      an elementary mixed meal (46 kJ/kg) over 4 h, first without and 3 mo later with
      approximately 300 mL red wine. Postprandial glucose concentrations were
      maintained at <10 mmol/L. RESULTS: Postprandially, the FSR of fibrinogen was
      approximately 30% greater (21.5 +/- 6.6% compared with 14.1 +/- 3.6% of pool/d; P
      < 0.01) and glucagon concentrations were approximately 40% greater (103 +/- 20
      compared with 61 +/- 13 ng/L; P < 0.015) with wine than without wine. However,
      the FSR of albumin and the rates of appearance of total and endogenous
      phenylalanine and leucine were not significantly different between treatments.
      First-pass splanchnic uptake (in micromol*kg(-1)*min(-1)) of dietary
      phenylalanine (0.22 +/- 0.02 compared with 0.19 +/- 0.02) and leucine (0.25 +/-
      0.04 compared with 0.14 +/- 0.02) were greater with wine (P < 0.05), whereas
      dietary phenylalanine oxidation was lower with wine, by approximately 25% (0.10
      +/- 0.02 compared with 0.14 +/- 0.01 micromol.kg(-1).min(-1); P < 0.05). Selected
      amino acid concentrations were significantly lower but glutamate concentrations
      were significantly higher with wine. CONCLUSIONS: In insulin-infused patients
      with type 1 diabetes, moderate wine intake with a meal resulted in 1) a higher
      fibrinogen FSR, glucagon concentration, and first-pass splanchnic uptake of
      leucine and phenylalanine; 2) lower dietary phenylalanine oxidation; 3) selective
      changes in plasma amino acid concentrations; 4) and no impairment in endogenous
      proteolysis and albumin synthesis.

PMID- 11976161
TI  - Plasma beta-carotene and retinol concentrations of children increase after a 30-d
      supplementation with the fruit Momordica cochinchinensis (gac).
AB  - BACKGROUND: In rural Vietnam, vitamin A deficiency is a concern. Among the
      indigenous fruit and vegetables, Momordica cochinchinensis (gac) fruit has been
      identified as having the highest beta-carotene concentration. Locally, it is
      mixed with rice in a preparation called xoi gac. OBJECTIVE: The purpose of this
      study was to assess this beta-carotene- rich rice preparation as a source of
      provitamin A for children in rural Vietnam. DESIGN: Preschoolers (n = 185)
      participated in a 30-d controlled supplementation trial. Children with low
      hemoglobin concentrations were assigned to 1 of 3 groups: a fruit group, who
      received xoi gac that contained 3.5 mg beta-carotene per serving; a powder group,
      who received rice mixed with 5.0 mg synthetic beta-carotene powder; and a control
      group, who received rice without fortification. RESULTS: The mean increase in
      plasma beta-carotene concentrations in the fruit and powder groups was
      significantly greater than that in the control group (P < 0.0001). After
      supplementation, the mean plasma retinol concentration in the fruit group was
      significantly higher than that in the control (P = 0.006) and powder (P = 0.0053)
      groups. Among the children with initial hemoglobin concentrations <or=110 g/L,
      the mean increase in hemoglobin concentrations in the fruit group was marginally
      higher than that in the control group (P = 0.017) but was not significantly
      different from that in the powder group. CONCLUSIONS: beta-Carotene from xoi gac
      is a good source of provitamin A carotenoids. Severely anemic children might
      particularly benefit from routine xoi gac consumption

PMID- 11976162
TI  - Inverse association of tea and flavonoid intakes with incident myocardial
      infarction: the Rotterdam Study.
AB  - BACKGROUND: Dietary flavonoids may protect against cardiovascular disease, but
      evidence is still conflicting. Tea is the major source of flavonoids in Western
      populations. OBJECTIVE: The association of tea and flavonoid intake with incident
      myocardial infarction was examined in the general Dutch population. DESIGN: A
      longitudinal analysis was performed with the use of data from the Rotterdam Study
      a population-based study of men and women aged >or=55 y. Diet was assessed at
      baseline (1990-1993) with a validated semiquantitative food-frequency
      questionnaire. The analysis included 4807 subjects with no history of myocardial
      infarction, who were followed until 31 December 1997. Data were analyzed in a Cox
      regression model, with adjustment for age, sex, body mass index, smoking status,
      pack-years of cigarette smoking, education level, and daily intakes of alcohol,
      coffee, polyunsaturated fat, saturated fat, fiber, vitamin E, and total energy.
      RESULTS: During 5.6 y of follow-up, a total of 146 first myocardial infarctions
      occurred, 30 of which were fatal. The relative risk (RR) of incident myocardial
      infarction was lower in tea drinkers with a daily intake >375 mL (RR: 0.57; 95%
      CI: 0.33, 0.98) than in nontea drinkers. The inverse association with tea
      drinking was stronger for fatal events (0.30; 0.09, 0.94) than for nonfatal
      events (0.68; 0.37, 1.26). The intake of dietary flavonoids (quercetin +
      kaempferol + myricetin) was significantly inversely associated only with fatal
      myocardial infarction (0.35; 0.13, 0.98) in upper compared with lower tertiles of
      intake. CONCLUSIONS: An increased intake of tea and flavonoids may contribute to
      the primary prevention of ischemic heart disease.

PMID- 11976163
TI  - Dietary silicon intake and absorption.
AB  - BACKGROUND: Increasing evidence suggests that silicon is important in bone
      formation. The main source of silicon for humans is the diet, but the
      bioavailability of silicon from solid foods is not well understood. OBJECTIVE: We
      estimated the dietary intake of silicon by adults, separately for men and women
      and for different age groups. Foods that were major contributors to silicon
      intake were identified. We then estimated the gastrointestinal uptake of silicon
      from major food sources and studied how uptake correlated with the silicon
      contents of the foods. DESIGN: Silicon intakes were determined in cohorts from
      the original Framingham Study and the Framingham Offspring Study by using a 126
      item food-frequency questionnaire. Gastrointestinal uptake of silicon from foods
      was estimated in 3-8 healthy subjects by using urinary silicon excretion as a
      surrogate measure of silicon uptake. RESULTS: Mean silicon intakes in men (30 and
      33 mg/d in the original Framingham and Framingham Offspring cohorts,
      respectively) were significantly higher than those in women (24 and 25 mg/d in
      the 2 cohorts, respectively; P = 0.0001). Silicon intake decreased with age (P <
      0.001, adjusted for sex). The major food sources were beer and bananas in men and
      bananas and string beans in women. Silicon was readily available from foods; a
      mean of 41% of the ingested silicon was excreted in urine. The silicon content of
      the foods consumed was significantly correlated with urinary silicon excretion (P
      = 0.019). CONCLUSIONS: Solid foods are a major source of available silicon. The
      association between dietary silicon intake and bone health should now be
      investigated.

PMID- 11976164
TI  - Grape seed proanthocyanidins improved cardiac recovery during reperfusion after
      ischemia in isolated rat hearts.
AB  - BACKGROUND: Increasing evidence shows that red wine consumption has
      cardioprotective effects. These effects have been attributed to the polyphenolic
      compounds in grapes. OBJECTIVE: We studied the effects of red grape seed
      proanthocyanidins on the recovery of postischemic function in isolated rat
      hearts. DESIGN: Two groups of rats were fed different doses of proanthocyanidin
      rich extract for 3 wk and another group was untreated and served as controls. The
      animals were then anesthetized and the hearts were isolated and subjected to 30
      min of ischemia followed by 2 h of reperfusion. Coronary effluents were collected
      during the third minute of reperfusion for measurement of oxygen free radicals by
      using electron spin resonance spectroscopy. RESULTS: In rats treated with 50 and
      100 mg grape seed proanthocyanidins/kg, the incidence of reperfusion-induced
      ventricular fibrillation was reduced from its control value of 92% to 42% and
      25%, respectively (P < 0.05 for both). The incidence of ventricular tachycardia
      showed the same pattern. In rats treated with 100 mg proanthocyanidins/kg, the
      recovery of coronary flow, aortic flow, and developed pressure after 60 min of
      reperfusion was improved by 32% +/- 8%, 98% +/- 8%, and 37% +/- 3%, respectively
      (P < 0.05 for all) compared with untreated control rats. Electron spin resonance
      studies indicated that proanthocyanidins significantly inhibited the formation of
      oxygen free radicals. In rats treated with 100 mg proanthocyanidins/kg, free
      radical intensity was reduced by 75% +/- 7% (P < 0.05) compared with the control
      rats. CONCLUSION: Grape seed proanthocyanidins have cardioprotective effects
      against reperfusion-induced injury via their ability to reduce or remove,
      directly or indirectly, free radicals in myocardium that is reperfused after
      ischemia.

PMID- 11976165
TI  - Variability in conversion of beta-carotene to vitamin A in men as measured by
      using a double-tracer study design.
AB  - BACKGROUND: The vitamin A activity of beta-carotene is variable and surprisingly
      low in women. The reasons for this are not well understood. The vitamin A
      activity of beta-carotene in men is still uncertain. Contributions of dietary
      factors compared with individual traits are largely unknown. OBJECTIVE: Our
      objective was to measure the intrinsic variability in the vitamin A activity of
      beta-carotene among healthy, well-fed men living in a controlled environment.
      DESIGN: We used a double-tracer test-retest design. We dosed 11 healthy men
      orally with 30 micromol hexadeuterated (D6) retinyl acetate (all-trans
      19,19,19,20,20,20-[2H6]retinyl acetate) and then with 37 micromol D6 beta
      carotene (19,19,19,19',19',19'-[2H6]beta-carotene) 1 wk later. Doses were taken
      with breakfasts containing 16 g fat. We measured D6 retinol, D6 beta-carotene,
      and trideuterated (D3) retinol (derived from D6 beta-carotene) concentrations in
      plasma. Areas under the plasma concentration x time since dosing curves (AUCs)
      were determined for D6 retinol, D6 beta-carotene, and D3 retinol. RESULTS: All
      men had detectable D6 retinol concentrations in plasma. The mean (+/-SE)
      absorption of D6 beta-carotene in all subjects was 2.235 +/- 0.925%, and the mean
      conversion ratio was 0.0296 +/- 0.0108 mol retinol to 1 mol beta-carotene. Only 6
      of 11 men had sufficient plasma concentrations of D6 beta-carotene and D3 retinol
      that we could measure. The mean absorption of D6 beta-carotene in these 6
      subjects was 4.097 +/- 1.208%, and the mean conversion ratio was 0.0540 +/-
      0.0128 mol retinol to 1 mol beta-carotene. CONCLUSION: The vitamin A activity of
      beta-carotene, even when measured under controlled conditions, can be
      surprisingly low and variable.

PMID- 11976166
TI  - Homocysteine, B vitamin status, and cognitive function in the elderly.
AB  - BACKGROUND: Old age is associated with reduced cognitive performance. Nutritional
      factors may contribute to this association. OBJECTIVE: We tested associations
      between cognitive performance and plasma vitamin B-12, folate, and homocysteine
      concentrations in the elderly. DESIGN: We studied survivors of the Scottish
      Mental Surveys of 1932 (Aberdeen 1921 Birth Cohort, or ABC21) and 1947 (Aberdeen
      1936 Birth Cohort, or ABC36), which surveyed childhood intelligence quotient. We
      measured folate, vitamin B-12, and homocysteine concentrations in fasting blood
      samples and cognitive performance by the Mini Mental State Examination (MMSE),
      National Adult Reading Test (NART), Raven's Progressive Matrices (RPM), Auditory
      Verbal Learning Test (AVLT), digit symbol (DS) subtest, and block design (BD)
      subtest. RESULTS: Homocysteine was higher in the ABC21 than in the ABC36 (P <
      0.0001). There were positive correlations between folate and vitamin B-12 and
      negative correlations between homocysteine and both folate and vitamin B-12.
      MMSE, RPM, AVLT, DS, and BD scores were higher in the ABC36. In the ABC21,
      folate, vitamin B-12, and MMSE score were positively correlated and homocysteine
      was negatively correlated with RPM, DS, and BD scores. Folic acid was positively
      correlated with AVLT and DS scores. In the ABC36, folate was positively
      correlated with BD score. After adjustment for childhood intelligence quotient,
      partial correlations were strengthened between vitamin B-12 and NART score and
      between homocysteine and RPM score but weakened between red blood cell folate and
      DS score. CONCLUSIONS: B vitamins and homocysteine are associated with cognitive
      variation in old age. In the ABC21 but not the ABC36, homocysteine accounted for
      approximately 7-8% of the variance in cognitive performance. This may prove
      relevant to the design of neuroprotective studies in late life.

PMID- 11976167
TI  - Breast-feeding protects against celiac disease.
AB  - BACKGROUND: Celiac disease, or permanent gluten-sensitive enteropathy, is an
      immunologic disease strictly dependent on exposure to wheat gluten or related
      proteins in rye and barley. OBJECTIVE: The aim of this study was to explore
      whether breast-feeding and the mode of introducing dietary gluten influence the
      risk of celiac disease in childhood. DESIGN: A population-based incident case
      referent study of Swedish children, 627 cases with celiac disease and 1254
      referents, was conducted; 78% of the matched sets were included in the final
      analyses. A questionnaire was used to assess patterns of food introduction to
      infants. Models were built, based on current epidemiologic and immunologic
      knowledge of celiac disease, to study the potential influence of dietary patterns
      on disease risk and were evaluated by conditional logistic regression in
      multivariate analyses. RESULTS: The risk of celiac disease was reduced in
      children aged <2 y if they were still being breast-fed when dietary gluten was
      introduced [adjusted odds ratio (OR): 0.59; 95% CI: 0.42, 0.83]. This effect was
      even more pronounced in infants who continued to be breast-fed after dietary
      gluten was introduced (OR: 0.36; 95% CI: 0.26, 0.51). The risk was greater when
      gluten was introduced in the diet in large amounts (OR: 1.5; 95% CI: 1.1, 2.1)
      than when introduced in small or medium amounts. In older children, these risk
      factors were of no or only minor importance. CONCLUSIONS: The gradual
      introduction of gluten-containing foods into the diet of infants while they are
      still being breast-fed reduces the risk of celiac disease in early childhood and
      probably also during the subsequent childhood period.

PMID- 11976168
TI  - Distribution of the H+/peptide transporter PepT1 in human intestine: up-regulated
      expression in the colonic mucosa of patients with short-bowel syndrome.
AB  - BACKGROUND: Intestinal adaptation after massive bowel resection in animal models
      is characterized by increased gut-mucosal growth and expression of nutrient
      transporters. Few data about these indexes exist in humans with short-bowel
      syndrome (SBS). OBJECTIVE: The objective was to compare small-bowel and colonic
      mucosal growth and expression of the peptide transporter PepT1 in adults with or
      without SBS. DESIGN: Mucosal biopsy specimens were obtained from the small bowel
      and colon of 33 control subjects with intact intestine and from 13 SBS patients
      dependent on parenteral nutrition because of chronic malabsorption. Gut-mucosal
      crypt depth, villus height, and villus width were measured, and expression of
      PepT1 was determined by Northern blotting, in situ hybridization, and
      immunohistochemistry. RESULTS: The indexes of small-bowel and colonic mucosal
      growth were not significantly different between the 2 groups. PepT1 expression
      was high in the apical region of duodenal, jejunal, and ileal villus epithelial
      cells; low in absorptive colonocytes; and not significantly different in the
      distal small intestine of the 2 groups. However, the abundance of PepT1 mRNA in
      the colon of SBS patients was more than 5-fold that in control subjects (P <
      0.01). CONCLUSIONS: Gut adaptation in SBS patients does not appear to involve an
      increase in gut-mucosal crypt depth or villus size. PepT1 is abundant along the
      small-bowel brush border in humans; expression in the colon indicates that the
      large intestine has a mechanism for luminal di- and tripeptide transport. Up
      regulation of colonic PepT1 in SBS may adaptively improve accrual of malabsorbed
      di- and tripeptides, independent of changes in the mucosal surface area.

PMID- 11976169
TI  - Patterns of plasma leptin and insulin concentrations in hospitalized patients
      after the initiation of total parenteral nutrition.
AB  - BACKGROUND: The regulation of leptin in patients with critical illness is poorly
      understood. Sex, diet, body mass, and cytokines may all play a role. OBJECTIVE:
      The aims of this study were to determine the factors influencing leptin
      concentrations in hospitalized patients beginning total parenteral nutrition
      (TPN) and whether a 3-d regimen of TPN would further increase plasma leptin
      concentrations above baseline. DESIGN: Twenty-six patients requiring TPN were
      enrolled in this prospective, nonintervention study. Only 20 (11 women and 9 men)
      completed all 3 d of TPN. RESULTS: Baseline plasma leptin in the TPN patients
      ranged from 62.5 to 1625 pmol/L ( +/- SD: 419 +/- 387; n = 26) and was not
      significantly different between men (444 +/- 494 pmol/L) and women (363 +/- 244
      pmol/L). Baseline plasma insulin ranged from 76 to 695 pmol/L (271 +/- 188; n =
      26) and was not correlated with plasma leptin. Leptin concentrations increased
      after 3 d of TPN, from 356 +/- 300 to 794 +/- 600 pmol/L (P < 0.05) in parallel
      with an increase in insulin from 257 +/- 187 to 979 +/- 917 pmol/L (P < 0.01) in
      the 20 patients who completed the study; however, the changes were not correlated
      when expressed as percentages. Although the men and women had insulin responses
      to feeding that were not significantly different, leptin concentrations did not
      increase significantly in men but increased 3-fold in women (to 1094 +/- 638
      pmol/L; P < 0.01). CONCLUSIONS: Leptin regulation in patients with a critical
      illness differs substantially from that in healthy persons. The importance of
      glucose and insulin in leptin secretion remains unclear, especially in men.

PMID- 11976170
TI  - Fruit and vegetable intakes and the risk of colorectal cancer in the Breast
      Cancer Detection Demonstration Project follow-up cohort.
AB  - BACKGROUND: Recent findings have cast doubt on the hypothesis that high intakes
      of fruit and vegetables are associated with a reduced risk of colorectal cancer.
      OBJECTIVE: In a large prospective cohort of women, we examined the association
      between fruit and vegetable intakes and colorectal cancer. DESIGN: Between 1987
      and 1989, 45490 women with no history of colorectal cancer satisfactorily
      completed a 62-item Block-National Cancer Institute food-frequency questionnaire.
      During 386142 person-years of follow-up, 314 women reported incident colorectal
      cancer, searches of the National Death Index identified an additional 106
      colorectal cancers, and a match with state registries identified another 65
      colorectal cancers for a total of 485 cases. We used Cox proportional hazards
      regression analysis to estimate the relative risks (RRs) and 95% CIs in both
      energy-adjusted and fully adjusted models. RESULTS: In models using the
      multivariate nutrient-density model of energy adjustment, RRs for increasing
      quintile of fruit consumption indicated no significant association with
      colorectal cancer [RR (95% CI)]: 1.00 (reference), 0.94 (0.70, 1.26), 0.85 (0.63,
      1.15), 1.07 (0.81, 1.42), and 1.09 (0.82, 1.44). For vegetable consumption, there
      was also no significant association in the multivariate nutrient-density model
      with increasing quintiles of consumption: 1.00 (reference), 0.77 (0.58, 1.02),
      0.83 (0.63, 1.10), 0.90 (0.69, 1.19), and 0.92 (0.70, 1.22). Additionally, 3
      alternative models of energy adjustment showed no significant association between
      increases in vegetable intake and the risk of colorectal cancer. CONCLUSION:
      Although the limitations of our study design and data merit consideration, this
      investigation provides little evidence of an association between fruit and
      vegetable intakes and colorectal cancer.

PMID- 11976171
TI  - Effect of liquid dietary supplements on energy intake in the elderly.
AB  - BACKGROUND: Undernutrition is a risk factor for increased mortality in older
      adults. Therapeutic intervention includes the administration of liquid dietary
      supplements. OBJECTIVE: We investigated the effect of liquid dietary supplements
      on satiation, satiety, and energy intake in older adults. DESIGN: This study had
      2 phases in a within-subject, repeated-measures design. The energy intake of 15
      elderly (aged >70 y) and 15 younger (aged 20-40 y) healthy subjects was measured
      after 4 liquid preloads: water, high fat, high carbohydrate, and high protein.
      The preloads were administered within 5 min of a test meal in phase 1 and >or=60
      min before the test meal in phase 2. Palatability, fullness, and hunger were
      assessed by using visual analogue scales. RESULTS: Mean energy consumption of the
      test meals was significantly lower in the older than in the younger subjects (P =
      0.001), as was mean macronutrient consumption of fat and carbohydrate (P = 0.002
      and 0.001, respectively). Mean energy intake and macronutrient consumption were
      higher in phase 2 than in phase 1 in both older and younger subjects (P < 0.05).
      Satiety lasted longer in older than in younger subjects after the high-protein
      and high-fat preloads (P = 0.001). CONCLUSION: In the elderly, administration of
      dietary supplements between meals instead of with meals may be more effective in
      increasing energy consumption.

PMID- 11976172
TI  - Abstention from filtered coffee reduces the concentrations of plasma homocysteine
      and serum cholesterol.

PMID- 11976173
TI  - Moderate alcohol consumption and the risk of cardiovascular disease.

PMID- 11976175
TI  - High-calcium diets and fracture prevention.

PMID- 11976176
TI  - Is dietary carbohydrate essential for human nutrition?

PMID- 11976179
TI  - Increasing healthy life span: conventional measures and slowing the innate aging
      process. Proceedings of the Ninth Congress of the International Association of
      Gerontology (IAG). June 27-30, 2001. Vancouver, British Columbia, Canada.

PMID- 11976180
TI  - Genetic and environmental influences on exceptional longevity and the AGE
      nomogram.
AB  - To live beyond the octogenarian years, population and molecular genetic studies
      of centenarian sibships indicate that genetic factors play an increasingly
      important role as the limit of life span is approached. These factors are likely
      to influence basic mechanisms of aging that in turn broadly influence
      susceptibility to age-related illnesses. Lacking genetic variations that
      predispose to disease as well as having variations that confer disease resistance
      (longevity enabling genes) are probably both important to achieving exceptional
      old age. The AGE (aging, genetics, environment) nomogram is introduced as an
      illustrative construct for understanding the influence of environmental and
      genetic factors on survival to various ages, depending on variations in the
      hypothesized relative importance of genes and environment to longevity. The rapid
      rise in the incidence of centenarians could indicate that many more people than
      we originally thought have the optimal set of genetic factors necessary to get to
      100 and beyond. Recent studies indicate the likelihood that such factors will be
      elucidated in the near future.

PMID- 11976181
TI  - Cell senescence in human aging and disease.
AB  - The most common causes of death and suffering, even in most underdeveloped
      nations, are age-related diseases. These diseases share fundamental and often
      unappreciated pathology at the cellular and genetic levels, through cell
      senescence. In cancer, enforcing cell senescence permits us to kill cancer cells
      without significantly harming normal cells. In other age-related diseases, cell
      senescence plays a direct role, and we may be able to prevent and reverse much of
      the pathology. While aging is attributed to "wear and tear," genetic studies show
      that these effects are avoidable (as is the case in germ cell lines) and occur
      only when cells down-regulate active (and sufficient) repair mechanisms,
      permitting degradation to occur. Aging occurs when cells permit accumulative
      damage by wear and tear, by altering their gene expression rather than vice
      versa. Using telomerase in laboratory settings, we can currently reset this
      pattern and its consequences both within cells and between cells. Doing so resets
      not only cell behavior but the pathological consequences within tissues
      comprising such cells. We can currently grow histologically young, reconstituted
      human skin using old human skin cells (keratinocytes and fibroblasts).
      Technically we could now test this approach in joints, vessels, the immune
      system, and other tissues. This model is consistent with all available laboratory
      data and known aging pathology. Within the next decade, we will be able to treat
      age-related diseases more effectively than ever before.

PMID- 11976182
TI  - Replicative aging, telomeres, and oxidative stress.
AB  - Aging is a very complex phenomenon, both in vivo and in vitro. Free radicals and
      oxidative stress have been suggested for a long time to be involved in or even to
      be causal for the aging process. Telomeres are special structures at the end of
      chromosomes. They shorten during each round of replication and this has been
      characterized as a mitotic counting mechanism. Our experiments show that the rate
      of telomere shortening in vitro is modulated by oxidative stress as well as by
      differences in antioxidative defence capacity between cell strains. In vivo we
      found a strong correlation between short telomeres in blood lymphocytes and the
      incidence of vascular dementia. These data suggest that parameters that
      characterise replicative senescence in vitro offer potential for understanding
      of, and intervention into, the aging process in vivo.

PMID- 11976183
TI  - Are changes of the cell membrane structure causally involved in the aging
      process?
AB  - Lipid peroxidation is recognized by proliferation, wounding, and aging. The
      connecting link between these different events is a change in cell wall
      structure, which activates membrane bound phospholipases. These cleave
      phospholipids. Thus liberated polyunsaturated fatty acids (PUFAs) are substrates
      for lipoxygenases, which accept equally well linoleic acid and arachidonic acid
      and generate lipid hydroperoxides (LOOHs). If the amount of free PUFAs exceeds a
      certain amount, lipoxygenases commit suicide. The consequence is liberation of
      free iron ions that react with LOOHs by formation of radicals. These start a
      chain reaction. LOO* radicals produced in the course of this process attack
      proteins, nucleic acids, and also double bonds of all unsaturated compounds by
      epoxidation. Morever LOOHs are decomposed to toxic epoxy acids and
      alphabetagammadelta-unsaturated aldehydes. Both species react with glutathione.
      The resulting products seem to induce apoptosis. Since the products generated by
      wounding or aging are formed by decomposition of LOOHs the investigation of the
      aging processes can be simplified by studying the physiological action of
      artificially generated lipid peroxidation products derived from pure PUFAs.
      Degradation products of LOOHs are generated by thermal decomposition of fat
      containing PUFAs. These products are induced into the body by adsorption in the
      intestine. They are at least partly incorporated in low density lipoproteins
      (LDLs). Primarily investigations seem to indicate that an overload of a diet rich
      in PUFAs induces only after two days an increase in oxidized LDL/PUFAs for a
      factor up to two in young people and for a factor of more than two in old
      individuals.

PMID- 11976184
TI  - Down-regulation of receptor-mediated endocytosis is responsible for senescence
      associated hyporesponsiveness.
AB  - Human diploid fibroblasts (HDF) do not divide indefinitely and eventually lead to
      an arrest of cell division by a process termed cellular or replicative
      senescence. Irreversible growth arrest of senescent cells is strongly related to
      the attenuated response to growth factors. Recently, we reported that up
      regulation of caveolin in the senescent cells is responsible for the attenuated
      response to growth factors. Senescent cells did not phosphorylate Erk-1/2 after
      EGF stimulation, whereas young cells did. In those senescent cells, we found an
      increased level of caveolin proteins and strong interactions between caveolin-1
      and EGFR. When we overexpressed caveolin-1 in young HDF, the activation of Erk
      1/2 on EGF stimulation was significantly suppressed. These results suggest that
      the hyporesponsiveness of senescent fibroblasts to EGF stimulation might be due
      to the overexpression of caveolin. In addition, the clathrin-dependent
      endocytosis system plays the more active and dominant role over the caveolae
      system. Therefore, we monitored the efficiency of clathrin-dependent receptor
      mediated endocytosis in the senescent cells in order to elucidate the exact mode
      of the attenuated response to growth factors in the senescent cells. Using a
      transferrin-uptake assay and Western blot analysis of endocytosis-related
      proteins, we found a significant decrease of amphiphysin-1 in human diploid
      fibroblasts of multipassages. By adjusting the level of amphiphysin, we could
      modulate the efficiency of receptor-mediated endocytosis either in young or old
      cells toward growth factors: that is, a dominant negative mutant of amphiphysin-1
      blocked the endocytosis in the young cells, while microinjection of the gene
      resumed its activity in the old cells. Taken together, we conclude that the loss
      of endocytotic activity of senescent cells is directly related to the down
      regulation of amphiphysin-1 and/or up-regulation of caveolins. This opens a new
      field of functional recovery of the senescent cells simply through adjusting the
      receptor-mediated endocytosis capacity.

PMID- 11976185
TI  - Dietary restriction initiated in late adulthood can reverse age-related
      alterations of protein and protein metabolism.
AB  - Many reports have been published on the effects of lifelong dietary restriction
      (DR) on a variety of parameters such as life span, carcinogenesis,
      immunosenescence, memory function, and oxidative stress. There is, however,
      limited available information on the effect of late onset DR that might have
      potential application to intervene in human aging. We have investigated the
      effect of DR initiated late in life on protein and protein degradation. Two
      months of DR in 23.5-month-old mice significantly reduced heat-labile altered
      proteins in the liver, kidney, and brain. DR reversed the age-associated increase
      in the half-life of proteins, suggesting that the dwelling time of the proteins
      is reduced in DR animals. In accordance with this observation, the activity of
      proteasome, which is suggested to be responsible for degradation of altered
      proteins, was found increased in the liver of rats 30 months of age subjected to
      3.5 months of DR. Thus, DR can increase turnover of proteins, thereby possibly
      attenuating potentially harmful consequences by altered proteins. Likewise, DR in
      old rats reduced carbonylated proteins in liver mitochondria, although the effect
      was not observed in cytosolic proteins. Fasting induced apoA-IV synthesis in the
      liver of young mice for efficient mobilization of stored tissue fats, while it
      occurred only marginally in the old. DR for 2 months from 23 months of age
      partially restored inducibility of this protein, suggesting the beneficial effect
      of DR. Taking all these findings together, it is conceivable that DR conducted in
      old age can be beneficial not only to retard age-related functional decline but
      also to restore functional activity in young rodents. Interestingly, recent
      evidence that involves DNA array gene expression analysis supports the findings
      on the age-related decrease in protein turnover and its reversion by late-onset
      DR.

PMID- 11976186
TI  - Pigments in aging: an overview.
AB  - Although during the normal aging process there are numerous pigmentary changes,
      the best recognized are those of melanin and lipofuscin. Melanin may increase
      (e.g., age spots, senile lentigo, or melanosis coli) or decrease (e.g., graying
      of hair or ocular melanin) with age, while lipofuscin (also called age pigment)
      always increases with age. In fact, the time-dependent accumulation of lipofuscin
      in lysosomes of postmitotic cells and some stable cells is the most consistent
      and phylogenetically constant morphologic change of aging. This pigment displays
      a typical autofluorescence (Ex: approximately 440; Em: approximately 600 nm),
      sudanophilia, argyrophilia, PAS positiveness, and acid fastness. Advances on its
      biogenesis, composition, evolution, and lysosomal degradation have been hampered
      by the persistent confusion between lipofuscin and the large family of ceroid
      pigments found in a variety of pathological conditions, as evidenced by the
      frequent use of the hybrid term lipofuscin/ceroid by investigators mainly working
      with in vitro systems of disputable relevance to in vivo lipofuscinogenesis.
      While lipofuscin and ceroid pigments may share some of their physicochemical
      properties at one moment or another in their evolutions, these pigments have
      different tissue distribution, rates of accumulation, origin of their precursors,
      and lectin binding affinities. Although it is widely believed that lipofuscin is
      a marker of oxidative stress, and that it can be, therefore, modified by
      antioxidants and prooxidants, these assumptions are mainly based on in vitro
      experiments and are not generally supported by in vivo studies. Another common
      misconception is the belief that lipofuscin can be extracted from tissues by
      lipid solvents and measured spectrofluorometrically. These and other disturbing
      problems are reviewed and discussed in this presentation.

PMID- 11976187
TI  - Aging and the role of reactive nitrogen species.
AB  - The role of reactive oxygen species and its effects on aging has received
      considerable attention in the past 47 years since Dr. Denham Harman first
      proposed the "free radical theory of aging." Though not completely understood due
      to the incalculable number of pathways involved, the number of manuscripts that
      facilitate the understanding of the underlying effects of reactive radical
      species on the oxidative stress on lipids, proteins, and DNA and its contribution
      to the aging process increases nearly exponentially each year. More recently, the
      role of reactive nitrogen species, such as nitric oxide and its by-products-
      nitrate (NO3-), nitrite (NO2-), peroxynitrite (ONOO-), and 3-nitrotyrosine--have
      been shown to have a direct role in cellular signaling, vasodilation, and immune
      response. Nitric oxide is produced within cells by the actions of a group of
      enzymes called nitric oxide synthases. Presently, there are three distinct
      isoforms of nitric oxide synthase: neuronal (nNOS or NOS-1), inducible (iNOS or
      NOS-2), and endothelial (eNOS or NOS-3), and several subtypes. While nitric oxide
      (NO*) is a relative unreactive radical, it is able to form other reactive
      intermediates, which could have an effect on protein function and on the function
      of the entire organism. These reactive intermediates can trigger nitrosative
      damage on biomolecules, which in turn may lead to age-related diseases due to
      structural alteration of proteins, inhibition of enzymatic activity, and
      interferences of the regulatory function. This paper will critically review the
      evidence of nitration and the important role it plays with aging. Furthermore, it
      will summarize the physiological role of nitration as well as the mechanisms
      leading to proteolytic degradation of nitrated proteins within biological
      tissues.

PMID- 11976188
TI  - Exercise-induced modulation of antioxidant defense.
AB  - Maintaining mobility is a critical element for the quality of life. Skeletal
      muscle, the primary organ for locomotion, undergoes age-associated deterioration
      in size, structure, and function. Recent research suggests that oxidative stress
      is an important etiology for sarcopenia. The level of oxidative stress imposed on
      aging muscle is influenced by two fundamental biological processes: the increased
      generation of reactive oxygen species (ROS) and age-associated changes in
      antioxidant defense. It appears that despite increased ROS production, aging
      muscle has a decreased gene expression of antioxidant enzymes possibly due to a
      diminished ability for cell signaling. A major benefit of nonexhaustive exercise
      is to induce a mild oxidative stress that stimulates the expression of certain
      antioxidant enzymes. This is mediated by the activation of redox-sensitive
      signaling pathways. For example, gene expression of muscle mitochondrial (Mn)
      superoxide dismutase is enhanced after an acute bout of exercise preceded by an
      elevated level of NF-kappaB and AP-1 binding. An increase in de novo protein
      synthesis of an antioxidant enzyme usually requires repeated bouts of exercise.
      Aging does not abolish but seems to attenuate training adaptations of antioxidant
      enzymes. Thus, for senescent muscle, training should be assisted with
      supplementation of exogenous antioxidants to research the optimal level of
      defense.

PMID- 11976189
TI  - The role of apoptosis in the normal aging brain, skeletal muscle, and heart.
AB  - During aging, there is a significant loss of some postmitotic cells, for example,
      cardiac and skeletal myocytes. Mitochondrial damage and dysfunction with age may
      trigger increased apoptosis, and this may explain this increase in cell loss.
      However, it is still unknown if apoptosis plays an important role in normal
      aging. In vitro it has been shown that several mitochondrial proteins can
      influence apoptosis, depending on factors such as the mitochondrial membrane
      potential and cellular redox status. It remains possible that mitochondrial
      dysfunction due to chronic oxidative stress with age is a cause of apoptosis in
      vivo. This cell loss may be due to mitochondrial-triggered apoptosis caused by
      age-associated increases in oxidant production or increased activation of
      mitochondrial permeability transition pores. Results from our laboratory and
      others are reviewed that relate to apoptosis in the normal aging of the brain
      cortex, heart, and skeletal muscle. Particular attention is paid to the role of
      cytochrome c release from mitochondria and alterations in the pro- and anti
      apoptotic proteins, Bax and Bcl-2, respectively. Our results demonstrate that a
      tissue-specific adaptation of the Bcl-2/Bax ratio occurs with age and may
      directly influence the release of cytochrome c.

PMID- 11976190
TI  - Generation of reactive oxygen and nitrogen species in contracting skeletal
      muscle: potential impact on aging.
AB  - Since the early 1980s biologists have recognized that skeletal muscle generates
      free radicals. Of particular interest are two closely related redox cascades-
      reactive oxygen species (ROS) and nitric oxide (NO) derivatives. The ROS cascade
      is initiated by superoxide anion radicals derived from the mitochondrial electron
      transport chain, the membrane-associated NAD(P)H oxidase complex, or other
      sources. NO is produced by two NO synthase isoforms constitutively expressed by
      muscle fibers. ROS and NO derivatives are produced continually and are detectable
      in both the cytosolic and extracellular compartments. Production increases during
      strenuous exercise. Both ROS and NO modulate contractile function. Under basal
      conditions, low levels of ROS enhance force production. Excessive ROS
      accumulation inhibits force, for example, during fatiguing exercise. NO inhibits
      skeletal muscle contraction, an effect that is partially mediated by cyclic GMP
      as a second messenger. With aging, redox modulation of muscle contraction may be
      altered by changes in the rates of ROS and NO production, the levels of
      endogenous antioxidants that buffer ROS and NO, and the sensitivities of
      regulatory proteins to ROS and NO action. The impact of aging on contractile
      regulation depends on the relative magnitude of these changes and their net
      effects on ROS and NO activities at the cellular level.

PMID- 11976191
TI  - Can exercise training improve immune function in the aged?
AB  - Many strategies have been used to improve immune function in the aged.
      Unfortunately, many of these interventions have been disappointing, impractical,
      costly to develop and administer, or accompanied by adverse side effects. Aside
      from dietary manipulation (caloric restriction without malnutrition or
      antioxidant supplementation), research involving behavioral preventative or
      restorative therapies has been lacking. Moderate exercise training has been shown
      to elicit beneficial outcomes in both the prevention and rehabilitation of many
      diseases of the elderly. It has been hypothesized that moderate levels of
      exercise improves, whereas strenuous exercise or overtraining suppresses, various
      immune function measures. Three general approaches have been implemented to study
      the impact of exercise on immune functioning in the elderly: (1) cross-sectional
      studies, (2) longitudinal studies, and (3) animal studies. In general, cross
      sectional studies examining highly active elderly have demonstrated improved in
      vitro T cell responses to polyclonal stimulation when compared to sedentary
      elderly. This is corroborated by several animal studies that have shown improved
      splenic T cell responses in vitro. Unfortunately, human prospective studies have
      failed to demonstrate consistent improvements in various measures of immune
      function in older adults. However, it should be cautioned that these studies have
      included small samples followed over a short duration, measuring a limited number
      of in vitro immune parameters, with some failing to account for potential
      confounding influences. Although such findings have the potential to be of
      substantial public health importance, very few systematic studies have been
      conducted.

PMID- 11976192
TI  - Fruit polyphenolics and brain aging: nutritional interventions targeting age
      related neuronal and behavioral deficits.
AB  - Nutritional interventions, in this case, increasing dietary intake of fruits and
      vegetables, can retard and even reverse age-related declines in brain function
      and in cognitive and motor performance in rats. Our lab has shown that as Fischer
      344 rats age their brains are increasingly vulnerable to oxidative stress.
      Dietary supplementation with fruit or vegetable extracts high in antioxidants
      (e.g., blueberry, BB, spinach, respectively) can decrease this vulnerability to
      oxidative stress as assessed in vivo by examining reductions in neuronal
      signaling and behavioral deficits and in vitro via H2O2-induced decrements in
      striatal synaptosomal calcium buffering. Examinations have also revealed that BB
      supplementations are effective in antagonizing other age-related changes in brain
      and behavior, as well as decreasing indices of inflammation and oxidative stress
      in gastrocnemius and quadriceps muscles. In ongoing studies we are attempting to
      determine the most effective BB polyphenolic components. To date, the
      anthocyanins show the most efficacy in penetrating the cell membrane and in
      providing antioxidant protection. In sum, our results indicate that increasing
      dietary intake of fruits and vegetables high in antioxidant activity may be an
      important component of a healthy living strategy designed to maximize neuronal
      and cognitive functioning into old age.

PMID- 11976193
TI  - Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and
      metabolites.
AB  - Mitochondria decay with age due to the oxidation of lipids, proteins, RNA, and
      DNA. Some of this decay can be reversed in aged animals by feeding them the
      mitochondrial metabolites acetylcarnitine and lipoic acid. In this review, we
      summarize our recent studies on the effects of these mitochondrial metabolites
      and mitochondrial antioxidants (alpha-phenyl-N-t-butyl nitrone and N-t-butyl
      hydroxylamine) on the age-associated mitochondrial decay of the brain of old
      rats, neuronal cells, and human diploid fibroblast cells. In feeding studies in
      old rats, these mitochondrial metabolites and antioxidants improve the age
      associated decline of ambulatory activity and memory, partially restore
      mitochondrial structure and function, inhibit the age-associated increase of
      oxidative damage to lipids, proteins, and nucleic acids, elevate the levels of
      antioxidants, and restore the activity and substrate binding affinity of a key
      mitochondrial enzyme, carnitine acetyltransferase. These mitochondrial
      metabolites and antioxidants protect neuronal cells from neurotoxin- and oxidant
      induced toxicity and oxidative damage; delay the normal senescence of human
      diploid fibroblast cells, and inhibit oxidant-induced acceleration of senescence.
      These results suggest a plausible mechanism: with age, increased oxidative damage
      to proteins and lipid membranes, particularly in mitochondria, causes a
      deformation of structure of enzymes, with a consequent decrease of enzyme
      activity as well as substrate binding affinity for their substrates; an increased
      level of substrate restores the velocity of the reaction and restores
      mitochondrial function, thus delaying mitochondrial decay and aging. This loss of
      activity due to coenzyme or substrate binding appears to be true for a number of
      other enzymes as well, including mitochondrial complex III and IV.

PMID- 11976194
TI  - Enhancing cognitive function across the life span.
AB  - Glucose administration regulates many neural and behavioral processes in rodents,
      including learning and memory. Given the important role of glucose in brain
      function and the safety of glucose as a treatment, we have investigated the
      effects of glucose administration in humans of different ages. In previous work,
      we examined the effects of early-morning glucose consumption on cognitive
      functions in elderly individuals. In this population, glucose enhanced
      performance on specific measures, particularly on those tasks where mild age
      related deficits appear (e.g., verbal declarative memory). Interestingly, glucose
      failed to enhance cognitive functions in young adults. Our recent work has
      examined three issues related to glucose enhancement of cognition: First, is
      glucose effective only in reversing impairments or can it also facilitate
      performance in highly functioning individuals? Second, are glucose effects
      dependent either on time of day or on interactions with other meals? Third, are
      typical breakfast foods as effective as glucose in enhancing cognitive
      performance? Our findings suggest that glucose can improve memory in highly
      functioning populations as it does in populations with deficits. However,
      enhancement by glucose may require sufficient levels of task difficulty and of
      blood glucose. In addition, like glucose, early morning consumption of cereal can
      improve performance on some cognitive tests. These results have important
      implications for the nature of glucose facilitation of memory and for the role of
      dietary factors in performance of many daily activities.

PMID- 11976195
TI  - Ascorbic acid, blood pressure, and the American diet.
AB  - A large controlled study supported by the NIH, the DASH study (Dietary Approaches
      to Stop Hypertension), demonstrated that a diet rich in fruits and vegetables can
      reduce blood pressure in persons with moderate elevation in blood pressure (BP).
      Fruits and vegetables are important sources of antioxidants such as vitamin C and
      carotenoids. We conducted a study in which we fed people a diet deficient in
      vitamin C for 30 days, followed for another 30 days by a diet adequate in vitamin
      C. Their blood levels of vitamin C and blood pressure (BP) were tracked. Plasma
      vitamin C was inversely related to diastolic blood pressure one month later
      (correlation = -0.48, P < 0.0001). Persons whose blood levels of vitamin C went
      down the furthest on depletion had the highest blood pressure one month later.
      Persons in the lowest one-fourth of the plasma vitamin C distribution had
      diastolic BP 7 mm Hg higher than did those in the upper one-fourth of the plasma
      ascorbic acid distribution. Multivariate control for age, body mass index, other
      plasma antioxidants, and dietary energy, calcium, fiber, sodium, and potassium
      did not reduce the plasma vitamin C effect. We believe that this indicates that
      the tissue stores of vitamin C may be important in regulating blood pressure. It
      is often thought that Americans' intake of vitamin C is ample, since the average
      intake is about 100 mg/day. However, this average level obscures the fact that
      substantial numbers of people actually have habitually low intake levels and low
      blood levels. African Americans tend to have low blood levels of vitamin C as
      well as the highest risk of hypertension. Low intake of antioxidant-rich fruits
      and vegetables may be one of the causes of hypertension.

PMID- 11976196
TI  - Toward mechanism-based antioxidant interventions: lessons from natural
      antioxidants.
AB  - It is generally accepted that one of the major and important contributions to
      skin aging, skin disorders, and skin diseases results from reactive oxygen
      species. More than other tissues, the skin is exposed to numerous environmental
      chemical and physical agents, such as ultraviolet light, causing oxidative
      stress. Accelerated cutaneous UV-induced aging, photo aging, is only one of the
      harmful effects of continual oxygen radical production in the skin.
      Interestingly, our ELISA assays of 8-oxo-2'-deoxyguanosine in skin of young and
      old Balb/c mice showed that cumene hydroperoxide-induced accumulation of the
      biomarker of oxidative DNA damage in skin of 32-week-old mice occurred
      independently of their vitamin E status, while no accumulation of oxo8-dG was
      detectable in the skin of young animals. This suggests that vitamin E is not the
      major protector of skin against cumene hydroperoxide-induced oxidative stress.
      Production and accumulation of apoptotic cells is one of the characteristic
      features of skin damage by oxidative stress that, in the absence of effective
      scavenging by macrophages, dramatically enhances oxidative damage and
      inflammatory response. In our model experiments, we demonstrated that Cu-OOH
      induces significant oxidative stress in phospholipids of normal human epidermal
      keratinocytes (NHEK) whose characteristic feature is an early and profound
      oxidation of phosphatidylserine (PS), likely related to PS externalization. Since
      externalized PS is a signal for recognition of apoptotic cells by macrophage
      scavenger receptors, PS oxidation may be translatable into elimination of thus
      damaged NHEKs. Experiments are now underway to determine whether inhibition of PS
      oxidation by antioxidants may interfere with important signaling functions of
      oxidative stress in eliminating apoptotic cells.

PMID- 11976198
TI  - Programmed death phenomena: from organelle to organism.
AB  - Programmed death phenomena appear to be inherent not only in living cells
      (apoptosis), but also in subcellular organelles (e.g., self-elimination of
      mitochondria, called mitoptosis), organs (organoptosis), and even whole organisms
      (phenoptosis). In all these cases, the "Samurai law of biology"--it is better to
      die than to be wrong--seems to be operative. The operation of this law helps
      complicated living systems avoid the risk of ruin when a system of lower
      hierarchic position makes a significant mistake. Thus, mitoptosis purifies a cell
      from damaged and hence unwanted mitochondria; apoptosis purifies a tissue from
      unwanted cells; and phenoptosis purifies a community from unwanted individuals.
      Defense against reactive oxygen species (ROS) is probably one of the primary
      evolutionary functions of programmed death mechanisms. So far, it seems that ROS
      play a key role in the mito-, apo-, organo-, and phenoptoses, which is consistent
      with Harman's theory of aging. Here a concept is described that tries to unite
      Weismann's hypothesis of aging as an adaptive programmed death mechanism and the
      generally accepted alternative point of view that considers aging as an
      inevitable result of accumulation in an organism of occasional injuries. It is
      suggested that injury accumulation is monitored by a system(s) actuating a
      phenoptotic death program when the number of injuries reaches some critical
      level. The system(s) in question are organized in such a way that the lethal case
      appears to be a result of phenoptosis long before the occasional injuries make
      impossible the functioning of the organism. It is stressed that for humans these
      cruel regulations look like an atavism that, if overcome, might dramatically
      prolong the human life span.

PMID- 11976197
TI  - Role of mitochondria in oxidative stress and aging.
AB  - The mitochondrial respiratory chain is a powerful source of reactive oxygen
      species (ROS), considered as the pathogenic agent of many diseases and of aging.
      We have investigated the role of Complex I in superoxide radical production and
      found by combined use of specific inhibitors of Complex I that the one-electron
      donor in the Complex to oxygen is a redox center located prior to the sites where
      three different types of coenzyme Q (CoQ) competitors bind, to be identified with
      an Fe-S cluster, most probably N2, or possibly an ubisemiquinone intermediate
      insensitive to all the above inhibitors. Short-chain coenzyme Q analogues enhance
      superoxide formation, presumably by mediating electron transfer from N2 to
      oxygen. The clinically used CoQ analogue idebenone is particularly effective,
      raising doubts about its safety as a drug. The mitochondrial theory of aging
      considers somatic mutations of mitochondrial DNA induced by ROS as the primary
      cause of energy decline; in rat liver mitochondria, Complex I appears to be most
      affected by aging and to become strongly rate limiting for electron transfer.
      Mitochondrial energetics is also deranged in human platelets upon aging, as
      demonstrated by the decreased Pasteur effect (enhancement of lactate production
      by respiratory inhibitors). Cells counteract oxidative stress by antioxidants:
      CoQ is the only lipophilic antioxidant to be biosynthesized. Exogenous CoQ,
      however, protects cells from oxidative stress by conversion into its reduced
      antioxidant form by cellular reductases. The plasma membrane oxidoreductase and
      DT-diaphorase are two such systems: likewise, they are overexpressed under
      oxidative stress conditions.

PMID- 11976199
TI  - Melatonin reduces oxidant damage and promotes mitochondrial respiration:
      implications for aging.
AB  - Melatonin has a number of properties as a consequence of which it could be
      beneficial to animals as they age. Of particular interest are its ubiquitous
      actions as a direct and indirect antioxidant and free radical scavenger. Besides
      directly detoxifying a variety of reactive oxygen and reactive nitrogen species,
      at least one product that is formed as a result of these interactions is also a
      potent free radical scavenger. Thus, the product that is formed when melatonin
      detoxifies hydrogen peroxide, that is, N1-acetyl-N2-formyl-5-methoxykynuramine is
      an efficient scavenger, at least equivalent to melatonin itself. This antioxidant
      cascade increases the ability of melatonin to resist oxidative damage. Other
      actions of melatonin, such as stimulation of antioxidative enzymes also improves
      its status as an antioxidant. Finally, recent observations documenting
      melatonin's ability to stimulate electron transport and ATP production in the
      inner-mitochondrial membrane also has relevance for melatonin as an agent that
      could alter processes of aging. These findings, coupled with diminished melatonin
      production in advanced age, has prompted scientists to consider melatonin in the
      context of aging. As of this writing there is no definitive evidence to prove
      that melatonin alters the rate of aging, although data relating to melatonin
      deferring some age-related degenerative conditions is accumulating rapidly.

PMID- 11976200
TI  - Metabolic alterations and shifts in energy allocations are corequisites for the
      expression of extended longevity genes in Drosophila.
AB  - Evolutionary theories suggest that the expression of extended longevity depends
      on the organism's ability to shift energy from reproduction to somatic
      maintenance. New data led us to reexamine our older data and integrate the two
      into a larger picture of the genetic and metabolic alterations required if the
      animal is to live long. Our Ra normal-lived control strain can express any one of
      three different extended longevity phenotypes, only one of which involves
      significant and proportional increases in both mean and maximum longevity and
      thus a delayed onset of senescence. This phenotype is dependent on the up
      regulation of the antioxidant defense system (ADS) genes and enzymes. Animals
      that express this phenotype typically have a pattern of altered specific
      activities in metabolically important enzymes, suggesting they are necessary to
      support the NAD+/NADP+ reducing system required for the continued high ADS enzyme
      activities. Fecundity data suggests that the energy required for this higher
      level of somatic maintenance initially came from a reduced egg production. This
      was only transient, however, for the females significantly increased their
      fecundity in later generations while still maintaining their longevity. The
      energy required for this enhanced fecundity was probably obtained from an
      increased metabolic efficiency, for the mitochondria of the La long-lived strain
      are metabolically more efficient and have a lower leakage of reactive oxygen
      species (ROS) to the cytosol. Selection pressures that do not lead to these
      shifts in energy allocations result in extended longevity phenotypes
      characterized by increased early survival or increased late survival but not by a
      delayed onset of senescence.

PMID- 11976202
TI  - Cognitive impairment of rats caused by oxidative stress and aging, and its
      prevention by vitamin E.
AB  - In order to verify whether brain damage caused by chronic oxidative stress
      induces the impairment of cognitive function, the ability of learning and memory
      was assessed using the water maze and the eight-arm radial maze tasks. Young rats
      showed significantly greater learning ability before the stress than the old and
      vitamin E-deficient rats. At five days after subjection to oxidative stress, the
      memory function of the young declined toward the level of that in the aged rats
      maintained under normal condition. This phenomenon is supported by the findings
      that the delayed-type apoptosis appeared in the CA1 region of the hippocampus of
      the young at five to seven days after the stress. Vitamin E supplementation to
      the young accelerated significantly their learning functions before the stress
      and prevented the deficit of memory caused by the stress. When rats were
      subjected to stress, thiobarbituric acid-reactive substance (TBARS), lipid
      hydroperoxides, and protein carbonyls were significantly increased in synaptic
      plasma membranes. It was found that zeta-potential of the synaptic membrane
      surface was remarkably decreased. These phenomena were also observed in the aged
      and vitamin E-deficient rats maintained under normal condition. These results
      suggest that oxidative damage to the rat synapse in the cerebral cortex and
      hippocampus during aging may contribute to the deficit of cognitive functions.

PMID- 11976201
TI  - Prevention of mitochondrial oxidative damage using targeted antioxidants.
AB  - Mitochondrial-targeted antioxidants that selectively block mitochondrial
      oxidative damage and prevent some types of cell death have been developed. These
      antioxidants are ubiquinone and tocopherol derivatives and are targeted to
      mitochondria by covalent attachment to a lipophilic triphenylphosphonium cation.
      Because of the large mitochondrial membrane potential, these cations accumulated
      within mitochondria inside cells, where the antioxidant moiety prevents lipid
      peroxidation and protects mitochondria from oxidative damage. The mitochondrially
      localized ubiquinone also protected mammalian cells from hydrogen peroxide
      induced apoptosis while an untargeted ubiquinone analogue was ineffective against
      apoptosis. When fed to mice these compounds accumulated within the brain, heart,
      and liver; therefore, using these mitochondrial-targeted antioxidants may help
      investigations of the role of mitochondrial oxidative damage in animal models of
      aging.

PMID- 11976203
TI  - Reaction of carnosine with aged proteins: another protective process?
AB  - Cellular aging is often associated with an increase in protein carbonyl groups
      arising from oxidation- and glycation-related phenomena and suppressed proteasome
      activity. These "aged" polypeptides may either be degraded by 20S proteasomes or
      cross-link to form structures intractable to proteolysis and inhibitory to
      proteasome activity. Carnosine (beta-alanyl-l-histidine) is present at
      surprisingly high levels (up to 20 mM) in muscle and nervous tissues in many
      animals, especially long-lived species. Carnosine can delay senescence in
      cultured human fibroblasts and reverse the senescent phenotype, restoring a more
      juvenile appearance. As better antioxidants/free-radical scavengers than
      carnosine do not demonstrate these antisenescent effects, additional properties
      of carnosine must contribute to its antisenescent activity. Having shown that
      carnosine can react with protein carbonyls, thereby generating "carnosinylated"
      polypeptides using model systems, we propose that similar adducts are generated
      in senescent cells exposed to carnosine. Polypeptide-carnosine adducts have been
      recently detected in beef products that are relatively rich in carnosine, and
      carnosine's reaction with carbonyl functions generated during amino acid
      deamidation has also been described. Growth of cultured human fibroblasts with
      carnosine stimulated proteolysis of long-labeled proteins as the cells approached
      their "Hayflick limit," consistent with the idea that carnosine ameliorates the
      senescence-associated proteolytic decline. We also find that carnosine suppresses
      induction of heme-oxygenase-1 activity following exposure of human endothelial
      cells to a glycated protein. The antisenescent activity of the spin-trap agent
      alpha-phenyl-N-t-butylnitrone (PBN) towards cultured human fibroblasts resides in
      N-t-butyl-hydroxylamine, its hydrolysis product. As hydroxylamines are reactive
      towards aldehydes and ketones, the antisenescent activity of N-t-butyl
      hydroxylamine and other hydroxylamines may be mediated, at least in part, by
      reactivity towards macromolecular carbonyls, analogous to that proposed for
      carnosine.

PMID- 11976204
TI  - Pharmacological interventions in aging and age-associated disorders: potentials
      of propargylamines for human use.
AB  - Past studies including our own have confirmed that chronic administration of
      deprenyl can prolong life spans of at least four different animal species.
      Pretreatment with the drug for several weeks increases activities of superoxide
      dismutase (SOD) and catalase (CAT) in selective brain regions. An up-regulation
      of antioxidant enzyme activities can also be induced in organs such as the heart,
      kidney, spleen, and adrenal gland, and all are accompanied by an increase in mRNA
      levels for SODs in these organs. The effect of deprenyl on enzyme activities has
      a dose-effect relationship of a typical inverted U shape. A similar inverted U
      shape also has emerged for the drug's effect on survival of animals. An apparent
      parallelism observed between these two effects of the drug seems to support our
      contention that the up-regulation of antioxidant enzymes is at least partially
      responsible for the life-prolonging effect on animals. Further, when a clinically
      applied dose of the drug for patients with Parkinson's disease was given to
      monkeys, SOD and CAT activities were increased in striatum of these monkeys,
      which suggests potential for the drug's applicability to humans. The drug was
      also found to increase concentrations of cytokines such as interleukin-1beta (IL
      1beta) and tumor necrosis factor-alpha (TNF-alpha) in the above rat organs.
      Together with past reports demonstrating that deprenyl increases natural killer
      (NK) cell functions and interferon-gamma, and prevents the occurrence of
      malignant tumors in rodents and dogs, the mobilization of these humoral factors
      may therefore be included as possible mechanisms of action of deprenyl for its
      diverse antiaging and life-prolonging effects. The potentials of propargylamines,
      (-)deprenyl in particular, for human use as antiaging drugs remain worthy of
      exploration in the future.

PMID- 11976205
TI  - Pharmacological interventions against aging through the cell plasma membrane: a
      review of the experimental results obtained in animals and humans.
AB  - As was shown in a recent review by this author (Ann. N.Y. Acad. Sci., 928: 187
      199, 2001), oxyradicals cannot be considered only as harmful by-products of the
      oxidative metabolism, but living cells and organisms implicitly require their
      production. This idea is supported by numerous facts and arguments, the most
      important of which is that the complete inhibition of the oxyradical production
      by KCN (or by any block of respiration) kills the living organisms long before
      the energy reserves would be exhausted. This new theoretical approach not only
      helps our understanding of the normal functions of the living organisms, such as
      the basic memory mechanisms in the brain cells, but also helps in identifying the
      site-specific, radical-induced damaging mechanisms that represent the undesirable
      side effects of oxygen free radicals. First of all, these effects make the cell
      plasma membrane vulnerable and cause a series of intracellular functional
      disorders, as described by the membrane hypothesis of aging (MHA). The logical
      way for any antiaging intervention therefore should be to increase the available
      number of loosely bound electrons inside the plasma membrane that are easily
      accessible for OH(*) free radical scavenging. The present review summarizes the
      available knowledge regarding the theory of the use of membrane-related antiaging
      pharmaca, like centrophenoxine (CPH), tested in both animal experiments and human
      clinical trials. A modified, developed version of CPH coded as BCE-001 is also
      reported.

PMID- 11976206
TI  - Nitrones as neuroprotectants and antiaging drugs.
AB  - Specific nitrones have been used for more than 30 years in analytical chemistry
      and biochemistry to trap and stabilize free radicals for the purpose of their
      identification and characterization. PBN (alpha-phenyl-tert-butyl nitrone), one
      of the more widely used nitrones for this purpose, has been shown to have potent
      pharmacologic activities in models of a number of aging-related diseases, most
      notably the neurodegenerative diseases of stroke and Alzheimer's disease. Studies
      in cell and animal models strongly suggest that PBN has potent antiaging
      activity. A novel nitrone, CPI-1429, has been shown to extend the life span of
      mice when administration was started in older animals. It has also shown efficacy
      in the prevention of memory dysfunction associated with normal aging in a mouse
      model. Mechanistic studies have shown that the neuroprotective activity of
      nitrones is not due to mass-action free radical-trapping activity, but due to
      cessation of enhanced signal transduction processes associated with
      neuroinflammatory processes known to be enhanced in several neurodegenerative
      conditions. Enhanced neuroinflammatory processes produce higher levels of
      neurotoxins, which cause death or dysfunction of neurons. Therefore, quelling of
      these processes is considered to have a beneficial effect allowing proper
      neuronal functioning. The possible antiaging activity of nitrones may reside in
      their ability to quell enhanced production of reactive oxygen species associated
      with age-related conditions. On the basis of novel ideas about the action of
      secretory products formed by senescent cells on bystander cells, it is postulated
      that nitrones will mitigate these processes and that this may be the mechanism of
      their antiaging activity.

PMID- 11976207
TI  - Therapeutics against mitochondrial oxidative stress in animal models of aging.
AB  - During the course of normal metabolism, reactive oxygen species (ROS) are
      produced from within the respiratory chain of the mitochondria. These ROS have
      the capacity to oxidize and damage a variety of cellular constituents including
      lipids, DNA, and proteins. We have taken a genetic and pharmacological approach
      in delineating the range of molecular targets that can be oxidatively damaged by
      mitochondrial ROS. Specifically, we use mice that are lacking the mitochondrial
      form of superoxide dismutase (sod 2(-/-) mice) to better understand the possible
      phenotypes that can arise from mitochondrial oxidative stress. sod 2(-/-) mice
      can be used to test the efficacy of antioxidants, and more generally the efficacy
      of antioxidants against mitochondrial oxidative stress. We have evaluated
      superoxide dismutase/catalase mimetics in this mammalian model of mitochondrial
      oxidative stress, and have shown a high degree of efficacy in protecting against
      ROS produced within the mitochondria. Similarly, we have employed the nematode
      Caenorhabditis elegans to test the hypothesis that effective antioxidant therapy
      can prolong the life span of an invertebrate.

PMID- 11976208
TI  - A unified mechanism in the initiation of cancer.
AB  - Estrogens are involved in the initiation of breast, prostate, and other kinds of
      human cancer. In this process, the endogenous estrogens, estrone and estradiol,
      are metabolized to 2-catechol estrogens (2-CE, major) and 4-CE (minor). If the 4
      CEs are further oxidized to CE-3,4-quinones, they may react with DNA to form
      depurinating adducts at N-7 of guanine and N-3 of adenine, and generate apurinic
      sites. Similarly, the carcinogenic synthetic estrogen hexestrol, a hydrogenated
      derivative of diethylstilbestrol, is metabolized to its quinone, which reacts
      with DNA to form analogous depurinating adducts. This could be the primary
      critical event leading to oncogenic mutations and then initiation of cancer.
      Evidence supporting this hypothesis has been obtained from the human breast and
      animal models susceptible to estrogen-induced tumors, including the Syrian golden
      hamster kidney, ACI rat mammary gland, and Noble rat prostate. The oxidation of
      phenols to catechols and then to quinones is not only a mechanism of tumor
      initiation for natural and synthetic estrogens, but also for the leukemogen
      benzene. In fact, catechol, one of the metabolites of benzene, when oxidized to
      its quinone, reacts with DNA to form N7guanine and N3adenine depurinating
      adducts. Thus, a unifying mechanism, namely formation of catechol quinones and
      reaction with DNA, could initiate not only cancer by oxidation of specific
      endogenous estrogen metabolites, but also leukemia by oxidation of benzene.

PMID- 11976209
TI  - Coenzyme Q10 protects the aging heart against stress: studies in rats, human
      tissues, and patients.
AB  - With aging of the population, increasing numbers of elderly patients are
      presenting for cardiac surgery. However, the results in the elderly are inferior
      to those in the young. A likely contributing factor is an age-related reduction
      in cellular energy production in the myocardium during surgery, which is known to
      induce aerobic and ischemic stress. The lipophilic antioxidant and mitochondrial
      respiratory chain redox coupler, coenzyme Q10 (CoQ10), has the potential to
      improve energy production in mitochondria by bypassing defective components in
      the respiratory chain as well as by reducing the effects of oxidative stress. We
      hypothesized that CoQ10 pretreatment prior to stress could improve the recovery
      of the myocardium after stress.

PMID- 11976210
TI  - The Maillard hypothesis on aging: time to focus on DNA.
AB  - Aging is the outcome of the contest between chemistry and biology in living
      systems. Chronic, cumulative chemical modifications compromise the structure and
      function of biomolecules throughout the body. Proteins with long life spans serve
      as cumulators of exposure to chemical damage, which is detectable in the form of
      advanced glycation and lipoxidation end products (AGEs, ALEs); amino acids
      modified by reactive oxygen, chlorine, and nitrogen species; and deamidated and
      racemized amino acids. Not all of these modifications are oxidative in nature,
      although oxidative reactions are an important source of age-related damage.
      Measurements of AGEs and ALEs in proteins are useful for assessing the rate and
      extent of Maillard reaction damage, but it is the damage to the genome that
      undoubtedly has the greatest effect on the viability of the organism. The extent
      of genomic damage represents a balance between the rate of modification and the
      rate and fidelity of repair. Damage to DNA accumulates not in the form of
      modified nucleic acids, but as chemically "silent" errors in repair-insertions,
      deletions, substitutions, transpositions, and inversions in DNA sequences-that
      affect the expression and structure of proteins. These mutations are random, vary
      from cell to cell, and are passed forward from one cell generation to another.
      Although they are not detectable in DNA by conventional analytical techniques,
      purines and pyrimidines modified by Maillard reaction intermediates may be
      detectable in urine, and studies on these compounds should provide insight into
      the role of Maillard reactions of DNA in aging and disease.

PMID- 11976211
TI  - Oxidative stress and programmed cell death in diabetic neuropathy.
AB  - Recent evidence in both animal models and human sural nerve biopsies indicates an
      association with oxidative stress, mitochondrial (Mt) membrane depolarization
      (MMD), and induction of programmed cell death (PCD). In streptozotocin (STZ)
      treated diabetic rats, hyperglycemia induces typical apoptotic changes as well as
      swelling and disruption of the Mt cristae in diabetic dorsal root ganglion
      neurons (DRG) and Schwann cells (SC), but these changes are only rarely observed
      in control neurons. In human sural nerve biopsies, from patients with diabetic
      sensory neuropathy, there is transmission electromicrograph evidence of swelling
      and disruption of the Mt and cristae compared to patients without peripheral
      neuropathy. In human SH-SY5Y neurons, rat sensory neurons, and SC, in vivo, there
      is an increase in reactive oxygen species (ROS) after exposure to 20 mM added
      glucose. In parallel, there is an initial Mt membrane hyperpolarization followed
      by depolarization (MMD). In turn, MMD is coupled with cleavage of caspases.
      Various strategies aimed at inhibiting the oxidative burst, or stabilizing the
      DeltaPsi(M), block induction of PCD. First, growth factors such as NGF can block
      induction of ROS and/or stabilize the DeltaPsi(M). This, in turn, is associated
      with inhibition of PCD. Second, reduction of ROS generation in neuronal Mt
      prevents neuronal PCD. Third, up-regulation of uncoupling proteins (UCPs), which
      stabilize the DeltaPsi(M), blocks induction of caspase cleavage. Collectively,
      these findings indicate that hyperglycemic conditions observed in diabetes
      mellitus are associated with oxidative stress-induced neuronal and SC death, and
      targeted therapies aimed at regulating ROS may prove effective in therapy of
      diabetic neuropathy.

PMID- 11976212
TI  - Alzheimer's disease: role of aging in pathogenesis.
AB  - Alzheimer's disease (AD) is characterized by intraneuronal fibrillary tangles,
      plaques, and cell loss. Brain lesions in both sporadic AD (SAD) and familial AD
      (FAD) are the same, and in the same distribution pattern, as those in individuals
      with Down syndrome (DS) and in smaller numbers in nondemented older individuals.
      Dementia onset is around 40 years for DS, 40-60 years for FAD, and usually over
      60 years for SAD. The different categories of AD may be due to processes that
      augment to different degrees the innate cellular aging rate, that is,
      mitochondrial superoxide radical (SO) formation. Thus, they increase the rate of
      accumulation of AD lesions. This lowers the age of onset into the dementia ranges
      associated with DS, FAD, and SAD, and concomitantly shortens life spans. Faster
      aging lowers AD onset age by decreasing the onset age for neurofibrillary tangle
      formation and neuronal loss, and the age when brain intercellular H2O2 can
      activate microglial cells. The early AD onset in DS is attributed to a defective
      mitochondrial complex 1. The proteins associated with FAD and their normal
      counterparts undergo proteolytic processing in the endoplasmic reticulum (ER).
      The mutated compounds increase the ratio of betaA42 to betaA40 and likely also
      down-regulate the ER calcium (Ca2+) buffering activity. Decreases in ER Ca2+
      content should increase the mitochondrial Ca2+ pool, thus enhancing SO formation.
      SAD may be due to increased SO formation caused by mutations in the approximately
      1000 genes involved in mitochondrial biogenesis and function. The hypothesis
      suggests measures to prevent and treat.

PMID- 11976213
TI  - Human aging and global function of coenzyme Q10.
AB  - In this paper, we review two parts of our recent work on human skeletal muscle.
      The first part mainly describes changes occurring during aging, whereas the
      second part discusses the functions of coenzyme Q10 (CoQ10), particularly in
      relation to the aging process. During the lifetime of an individual, mtDNA
      undergoes a variety of mutation events and rearrangements. These mutations and
      their consequent bioenergenic decline, together with nuclear DNA damage,
      contribute to the reduced function of cells and organs, especially in postmitotic
      tissues. In skeletal muscle, this functional decline can be observed by means of
      changes with age in fiber type profile and the reduction in the number and size
      of the muscle fibers. In addition to the functions of coenzyme Q10 as an electron
      carrier in the respiratory chain and as an antioxidant, CoQ10 has been shown to
      regulate global gene expression in skeletal muscle. We hypothesize that this
      regulation is achieved via superoxide formation with H2O2 as a second messenger
      to the nucleus.

PMID- 11976214
TI  - Mitochondrial DNA deletion mutations and sarcopenia.
AB  - This manuscript summarizes our studies on mitochondrial DNA and enzymatic
      abnormalities that accumulate, with age, in skeletal muscle. Specific quadricep
      muscles, rectus femoris in the rat and vastus lateralis in the rhesus monkey,
      were used in these studies. These muscles exhibit considerable sarcopenia, the
      loss of muscle mass with age. The focal accumulation of mtDNA deletion mutations
      and enzymatic abnormalities in aged skeletal muscle necessitates a histologic
      approach in which every muscle fiber is examined for electron transport system
      (ETS) enzyme activity along its length. These studies demonstrate that ETS
      abnormalities accumulate to high levels within small regions of aged muscle
      fibers. Concomitant with the ETS abnormalities, we observe intrafiber atrophy
      and, in many cases, fiber breakage. Laser capture microdissection facilitates
      analysis of individual fibers from histologic sections and demonstrates a tight
      association between mtDNA deletion mutations and the ETS abnormalities. On the
      basis of these results, we propose a molecular basis for skeletal muscle fiber
      loss with age, a process beginning with the mtDNA deletion event and culminating
      with muscle fiber breakage and loss.

PMID- 11976215
TI  - Involvement of mitochondria and other free radical sources in normal and abnormal
      fetal development.
AB  - Shepard and Mackler have documented quantitative increases in mitochondrial
      cristae between gestational days 10 and 14 in rats accompanied by decreased
      glucose utilization and increased NADH oxidase activity. Findings show a shift
      from glycolytic to oxidative metabolism starting at around the time of
      implantation. Exposure to many substances that cause transient uteroplacental
      hypoperfusion, including cocaine, phenytoin, calcium channel blockers, and nitric
      oxide synthase (NOS) inhibitors, induce limb and central nervous system (CNS)
      malformations while sparing the heart. We have reported that isolated electron
      transport particles prepared from sensitive tissues show reduced NADH oxidase
      activities compared with insensitive heart. They also have significantly greater
      superoxide formation in association with significantly reduced superoxide
      dismutase activities. NOS inhibitors induce severe limb reductions in late
      gestation. Exposure is associated with hemorrhage and nitrotyrosine (NT)
      formation shortly after treatment. Hemorrhage, malformations, and NT formation
      can be significantly reduced by coadministration of PBN, allopurinol, or
      aminoguanidine. On the basis of these findings, we have proposed a role for the
      formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in
      the genesis of limb reduction defects. It is important to note that limb
      reduction defects occur in humans ( approximately 0.22/1000) and have been
      associated with the agents listed above.

PMID- 11976216
TI  - Frequent intracellular clonal expansions of somatic mtDNA mutations: significance
      and mechanisms.
AB  - It has been proposed that age-dependent accumulation of somatic mutations in
      mtDNA is responsible for some aspects of the aging process. However, most cells
      contain hundreds to thousands of mtDNA molecules. Any nascent somatic mutant
      therefore appears as a single copy among a majority of wild-type species. A
      single mutant molecule is unlikely to influence the physiology of the cell and
      thus cannot play a role in the aging process. To affect cellular physiology, the
      nascent somatic mutants must somehow accumulate clonally in the cell to
      significant levels. The evidence supporting the view that, indeed, clonal
      expansion of mtDNA mutations is a widespread process in various human tissues,
      and the mechanisms by which clonal expansions may affect the aging process, are
      reviewed. Originally, clonal expansion was demonstrated for mtDNA with large
      deletions in muscle. Cell-by-cell analysis of human cardiomyocytes and buccal
      epithelial cells revealed that clonal expansion affects point mtDNA mutations as
      well as deletions. Expansions are not limited to muscle, but likely are present
      in most tissues, and almost every cell of an aged tissue is likely to be affected
      by an expansion. While the very existence of clonal expansion is beyond doubt,
      the mechanisms driving this process are largely controversial. The hypotheses
      explaining expansion includes random or various selective mechanisms, or both. We
      show that the spectra of expanded point mutations are drastically different in
      cardiomyocytes and epithelial cells. This suggests that the mechanisms of
      expansion in these tissues are different. In particular, we propose random
      segregation and positive selection models for epithelial and muscle cells,
      respectively.

PMID- 11976217
TI  - Mitochondrial damage in aging and apoptosis.
AB  - Mitochondria are essential to cellular aging, and free radical production by
      mitochondria is increased with aging. The rate of oxidant production by
      mitochondria correlates inversely with maximal life span of species. In many
      species, females live longer than males. We report that mitochondrial oxidant
      production by females is significantly lower than that of males. However,
      mitochondria from ovariectomized females have a similar oxidant production as
      those of males. Thus, gender difference in life span can be explained, at least
      in part, by different oxidant generation by mitochondria. Administration of
      antioxidants, such as vitamins C and E, or a Ginkgo biloba extract, protects
      against age-associated oxidative damage to mitochondrial DNA, oxidation of
      glutathione, and other signs of oxidative damage to mitochondria.

PMID- 11976218
TI  - Time to talk SENS: critiquing the immutability of human aging.
AB  - Aging is a three-stage process: metabolism, damage, and pathology. The
      biochemical processes that sustain life generate toxins as an intrinsic side
      effect. These toxins cause damage, of which a small proportion cannot be removed
      by any endogenous repair process and thus accumulates. This accumulating damage
      ultimately drives age-related degeneration. Interventions can be designed at all
      three stages. However, intervention in metabolism can only modestly postpone
      pathology, because production of toxins is so intrinsic a property of metabolic
      processes that greatly reducing that production would entail fundamental redesign
      of those processes. Similarly, intervention in pathology is a "losing battle" if
      the damage that drives it is accumulating unabated. By contrast, intervention to
      remove the accumulating damage would sever the link between metabolism and
      pathology, and so has the potential to postpone aging indefinitely. We survey the
      major categories of such damage and the ways in which, with current or
      foreseeable biotechnology, they could be reversed. Such ways exist in all cases,
      implying that indefinite postponement of aging--which we term "engineered
      negligible senescence"--may be within sight. Given the major demographic
      consequences if it came about, this possibility merits urgent debate.

PMID- 11976220
TI  - Oxidative stress and life span determination in the nematode Caenorhabditis
      elegans.
AB  - The free radical theory of aging proposes that oxidative stress is one of the
      determinants of an organism's life span. In Caenorhabditis elegans, genetic or
      environmental changes have been shown to modulate life span. Here we discuss
      whether changes in the generation and destruction of free radicals are implicated
      in these life span modulations. Changes in culture oxygen concentrations that are
      considered to reflect free radical generation perturb the life span. The life
      spans under high and low oxygen concentrations were shorter and longer,
      respectively, than those under normoxic conditions. Short-term exposure to high
      oxygen concentration lengthens the life span. This is considered to be the result
      of an increase in antioxidant defense induced by short-term oxidative stress.
      Mutations in genes such as age-1 and daf-2 that compose the insulin-like
      signaling network conferred oxidative stress resistance and an increase in Mn-SOD
      gene expression as well as life span extension.

PMID- 11976221
TI  - Membrane fatty acid unsaturation, protection against oxidative stress, and
      maximum life span: a homeoviscous-longevity adaptation?
AB  - Aging is a progressive and universal process originating endogenously that
      manifests during postmaturational life. Available comparative evidence supporting
      the mitochondrial free radical theory of aging consistently indicates that two
      basic molecular traits are associated with the rate of aging and thus with the
      maximum life span: the presence of low rates of mitochondrial oxygen radical
      production and low degrees of fatty acid unsaturation of cellular membranes in
      postmitotic tissues of long-lived homeothermic vertebrates in relation to those
      of short-lived ones. Recent research shows that steady-state levels of free
      radical-derived damage to mitochondrial DNA (mtDNA) and, in some cases, to
      proteins are lower in long- than in short-lived animals. Thus, nonenzymatic
      oxidative modification of tissue macromolecules is related to the rate of aging.
      The low degree of fatty acid unsaturation in biomembranes of long-lived animals
      may confer advantage by decreasing their sensitivity to lipid peroxidation.
      Furthermore, this may prevent lipoxidation-derived damage to other
      macromolecules. Taking into account the fatty acid distribution pattern, the
      origin of the low degree of membrane unsaturation in long-lived species seems to
      be the presence of species-specific desaturation pathways that determine membrane
      composition while an appropriate environment for membrane function is maintained.
      Mechanisms that prevent or decrease the generation of endogenous damage during
      the evolution of long-lived animals seem to be more important than trying to
      intercept those damaging agents or repairing the damage already inflicted. Here,
      the physiological meaning of these findings and the effects of experimental
      manipulations such as dietary stress, caloric restriction, and endocrine control
      in relation to aging and longevity are discussed.

PMID- 11976222
TI  - Mitochondrial decay in the aging rat heart: evidence for improvement by dietary
      supplementation with acetyl-L-carnitine and/or lipoic acid.
AB  - Mitochondrial decay has been postulated to be a significant underlying part of
      the aging process. Decline in mitochondrial function may lead to cellular energy
      deficits, especially in times of greater energy demand, and compromise vital ATP
      dependent cellular operations, including detoxification, repair systems, DNA
      replication, and osmotic balance. Mitochondrial decay may also lead to enhanced
      oxidant production and thus render the cell more prone to oxidative insult. In
      particular, the heart may be especially susceptible to mitochondrial dysfunction
      due to myocardial dependency on beta-oxidation of fatty acids for energy and the
      postmitotic nature of cardiac myocytes, which would allow for greater
      accumulation of mitochondrial mutations and deletions. Thus, maintenance of
      mitochondrial function may be important to maintain overall myocardial function.
      Herein, we review the major age-related changes that occur to mitochondria in the
      aging heart and the evidence that two such supplements, acetyl-l-carnitine
      (ALCAR) and (R)-alpha-lipoic acid, may improve myocardial bioenergetics and lower
      the increased oxidative stress associated with aging. We and others have shown
      that feeding old rats ALCAR reverses the age-related decline in carnitine levels
      and improves mitochondrial beta-oxidation in a number of tissues studied.
      However, ALCAR supplementation does not appear to reverse the age-related decline
      in cardiac antioxidant status and thus may not substantially alter indices of
      oxidative stress. Lipoic acid, a potent thiol antioxidant and mitochondrial
      metabolite, appears to increase low molecular weight antioxidant status and
      thereby decreases age-associated oxidative insult. Thus, ALCAR along with lipoic
      acid may be effective supplemental regimens to maintain myocardial function.

PMID- 11976223
TI  - Can antioxidant diet supplementation protect against age-related mitochondrial
      damage?
AB  - Harman's free radical theory of aging and our electron-microscopic finding of an
      age-related mitochondrial degeneration in the somatic tissues of the insect
      Drosophila melanogaster as well as in the fixed postmitotic Leydig and Sertoli
      cells of the mouse testis led us to propose a mitochondrial theory of aging,
      according to which metazoan senescence may be linked to oxygen stress-injury to
      the genome and membranes of the mitochondria of somatic differentiated cells.
      These concepts attract a great deal of attention, since, according to recent
      work, the mitochondrial damage caused by reactive oxygen species (ROS) and
      concomitant decline in ATP synthesis seem to play a key role not only in aging,
      but also in the fundamental cellular process of apoptosis. Although diet
      supplementation with antioxidants has not been able to increase consistently the
      species-characteristic maximum life span, it results in significant extension of
      the mean life span of laboratory animals. Moreover, diets containing high levels
      of antioxidants such as vitamins C and E seem able to reduce the risk of
      suffering age-related immune dysfunctions and arteriosclerosis. Presently, the
      focus of age-related antioxidant research is on compounds, such as deprenyl,
      coenzyme Q10, alpha-lipoic acid, and the glutathione-precursors thioproline and N
      acetylcysteine, which may be able to neutralize the ROS at their sites of
      production in the mitochondria. Diet supplementation with these antioxidants may
      protect the mitochondria against respiration-linked oxygen stress, with
      preservation of the genomic and structural integrity of these energy-producing
      organelles and concomitant increase in functional life span.

PMID- 11976224
TI  - The first six years at the National Institute for Longevity Sciences, Japan.
AB  - The National Institute for Longevity Sciences (NILS) of Japan opened on July 7,
      1995, 15 years after the Science Council of Japan recommended the establishment
      of the National Center for Aging and Geriatric Illnesses (the provisional name
      for NILS) in 1980. During the first four years of operation, 8 separate research
      departments, containing 21 laboratories, were established. NILS has both research
      departments for biomedical sciences, such as dementia research, molecular
      genetics, and geriatric research, and also departments of gerontechnology and the
      care of the elderly, which engage in research directed toward the comprehensive
      improvement of the health and well- being of the elderly. On July 9, 1995, the
      day of the opening ceremonies, NILS employed only three staff members, including
      the director general. At the end of fiscal year 2000 (March 31, 2001), the
      institute comprised a staff of more than 200 people, including 30 senior science
      staff and about 50 junior scientists. The Japanese government has recently
      decided to expand NILS to double its present size by the end of fiscal year 2004
      (March 2005).

PMID- 11976225
TI  - Gold for the NHS.

PMID- 11976226
TI  - Managing differentiated thyroid cancer.

PMID- 11976227
TI  - Lithium in bipolar mood disorder.

PMID- 11976228
TI  - Confronting the small arms pandemic.

PMID- 11976229
TI  - Health care and the European Union.

PMID- 11976230
TI  - NHS to receive an extra 40bn pound sterling over next five years.

PMID- 11976231
TI  - GPs get a new contract "to transform their lives".

PMID- 11976234
TI  - Amnesty team claims to have found human rights abuses in Jenin.

PMID- 11976236
TI  - Court rules that emergency contraception is lawful.

PMID- 11976237
TI  - New treatment improves symptoms of Parkinson's disease.

PMID- 11976238
TI  - Wanless report outlines "Rolls- Royce" health service for 2022.

PMID- 11976240
TI  - A qualitative study of action plans for asthma.
AB  - OBJECTIVES: To investigate the perspectives of patients with asthma on the use of
      an action plan and the implementation of this plan during an asthma attack that
      culminated in a visit to an emergency department. DESIGN: Qualitative study.
      SETTING: Tertiary teaching hospital, suburban hospital, and rural hospital.
      PARTICIPANTS: 62 patients aged 18 to 69 years who presented to an emergency
      department with asthma over a two month period. RESULTS: 29 participants
      described having action plans given to them by their doctors. Most patients with
      action plans reinterpreted their plan from the perspective of their own
      experiences with asthma. 33 patients did not have an action plan, the most common
      reason being that they had not been given one by their doctor. Some occupational
      groups were significantly less likely to have been given an action plan by their
      doctor than others. Most patients with an action plan found them useful for
      management of their asthma. CONCLUSIONS: Action plans were viewed positively by
      patients. Participants modified their prescribed plan according to their
      experience of asthma. To facilitate the implementation of a prescribed action
      plan, doctors need to acknowledge and include the patient's personal experience
      of their disease.

PMID- 11976239
TI  - Randomised trial of endoscopy with testing for Helicobacter pylori compared with
      non-invasive H pylori testing alone in the management of dyspepsia.
AB  - OBJECTIVE: To compare the efficacy of non-invasive testing for Helicobacter
      pylori with that of endoscopy (plus H pylori testing) in the management of
      patients referred for endoscopic investigation of upper gastrointestinal
      symptoms. DESIGN: Randomised controlled trial with follow up at 12 months.
      SETTING: Hospital gastroenterology unit. PARTICIPANTS: 708 patients aged under 55
      referred for endoscopic investigation of dyspepsia, randomised to non-invasive
      breath test for H pylori or endoscopy plus H pylori testing. MAIN OUTCOME
      MEASURE: Glasgow dyspepsia severity score at one year. Use of medical resources,
      patient oriented outcomes, and safety were also assessed. RESULTS: In 586
      patients followed up at 12 months the mean change in dyspepsia score was 4.8 in
      the non-invasive H pylori test group and 4.6 in the endoscopy group (95%
      confidence interval for difference -0.7 to 0.5, P=0.69). Only 8.2% of patients
      followed up who were randomised to breath test alone were referred for subsequent
      endoscopy. The use of non-endoscopic resources was similar in the two groups.
      Reassurance value, concern about missed pathology, overall patient satisfaction,
      and quality of life were similar in the two groups. The patients found the non
      invasive breath test procedure less uncomfortable and distressing than endoscopy
      with or without sedation. No potentially serious pathology requiring treatment
      other than eradication of H pylori was missed. CONCLUSION: In this patient group,
      non-invasive testing for H pylori is as effective and safe as endoscopy and less
      uncomfortable and distressing for the patient. Non-invasive H pylori testing
      should be the preferred mode of investigation.

PMID- 11976241
TI  - Decision making processes in people with symptoms of acute myocardial infarction:
      qualitative study.
AB  - OBJECTIVE: To identify the themes that influence decision making processes used
      by patients with symptoms of acute myocardial infarction. DESIGN: Qualitative
      study using semistructured interviews. SETTING: Two district hospitals in North
      Yorkshire. PARTICIPANTS: 22 patients admitted to hospital with confirmed second,
      third, or fourth acute myocardial infarction. MAIN OUTCOME MEASUREMENTS:
      Patients' perceptions of their experience between the onset of symptoms and the
      decision to seek medical help. RESULTS: Six main themes that influence the
      decision making process were identified: appraisal of symptoms, perceived risk,
      previous experience, psychological and emotional factors, use of the NHS, and
      context of the event. CONCLUSIONS: Knowledge of symptoms may not be enough to
      promote prompt action in the event of an acute myocardial infarction. Cognitive
      and emotional processes, individual beliefs and values, and the influence of the
      context of the event should also be considered in individual interventions
      designed to reduce delay in the event of symptoms of acute myocardial infarction.

PMID- 11976242
TI  - Prospective audit of records of deceased patients received in hospital mortuary.

PMID- 11976243
TI  - Research pointers: Unexplained differences in sex ratios at birth in Europe and
      North America.

PMID- 11976244
TI  - Treating Helicobacter pylori infection in primary care patients with
      uninvestigated dyspepsia: the Canadian adult dyspepsia empiric treatment
      Helicobacter pylori positive (CADET-Hp) randomised controlled trial.
AB  - OBJECTIVE: To determine whether a "test for Helicobacter pylori and treat"
      strategy improves symptoms in patients with uninvestigated dyspepsia in primary
      care. DESIGN: Randomised placebo controlled trial. SETTING: 36 family practices
      in Canada. PARTICIPANTS: 294 patients positive for H pylori ((13)C- urea breath
      test) with symptoms of dyspepsia of at least moderate severity in the preceding
      month. INTERVENTION: PARTICIPANTS were randomised to twice daily treatment for 7
      days with omeprazole 20 mg, metronidazole 500 mg, and clarithromycin 250 mg or
      omeprazole 20 mg, placebo metronidazole, and placebo clarithromycin. Patients
      were then managed by their family physicians according to their usual care. MAIN
      OUTCOME MEASURES: Treatment success defined as no symptoms or minimal symptoms of
      dyspepsia at the end of one year. Societal healthcare costs collected
      prospectively for a secondary evaluation of actual mean costs. RESULTS: In the
      intention to treat population (n=294), eradication treatment was significantly
      more effective than placebo in achieving treatment success (50% v 36%; P=0.02;
      absolute risk reduction=14%; number needed to treat=7, 95% confidence interval 4
      to 63). Eradication treatment cured H pylori infection in 80% of evaluable
      patients. Treatment success at one year was greater in patients negative for H
      pylori than in those positive for H pylori (54% v 39%; P=0.02). Eradication
      treatment reduced mean annual cost by $C53 (-86 to 180) per patient. CONCLUSIONS:
      A "test for H pylori with (13)C-urea breath test and eradicate" strategy shows
      significant symptomatic benefit at 12 months in the management of primary care
      patients with uninvestigated dyspepsia.

PMID- 11976245
TI  - Quitting and restarting smoking: cohort study of patients with angina in primary
      care.

PMID- 11976246
TI  - Science, medicine, and the future: Bioinformatics.

PMID- 11976247
TI  - ABC of clinical electrocardiography: Myocardial ischaemia.

PMID- 11976248
TI  - Health policy in the European Union: how it's made and how to influence it.

PMID- 11976249
TI  - Clinical screening for developmental dysplasia of the hip in Northern Ireland.
AB  - PROBLEM: The incidence of late diagnosed developmental dysplasia of the hip
      requiring surgery in Northern Ireland is high. The reported incidence was 1.14
      per 1000 children born during 1983-7. DESIGN: Comparative retrospective study.
      BACKGROUND AND SETTING: Clinical screening programme in Northern Ireland. Key
      measure for improvement: Reduced rate of operative intervention in children with
      developmental dysplasia of the hip detected after 6 months of age. STRATEGIES FOR
      CHANGE: Increased emphasis on staff training, introduction of a centralised nurse
      led clinic to improve access to orthopaedic surgeons, and increased use of
      ultrasonography. EFFECTS OF CHANGE: The incidence of developmental dysplasia of
      the hip diagnosed after 6 months in children born between January 1991 and
      December 1997 fell to 0.59 per 1000, presumably due to improved early detection.
      Nevertheless, 29 (16%) of the affected hips were not diagnosed when the child was
      first referred in the first 3 months of life. In addition, for 27 affected hips
      in children diagnosed after the age of 6 months there was a known risk factor
      (family history or breech delivery). LESSONS LEARNT: Improvements to screening
      processes can reduce late incidence of developmental dysplasia of the hip.
      Further steps to improve detection in children with known risk factors and rate
      of detection at first referral could reduce late presentation further.

PMID- 11976250
TI  - Global voices on HIV/AIDS. Unfairness of social and economic structures affect
      AIDS in Africa.

PMID- 11976251
TI  - Cancer isn't the only malignant disease. Palliative care can be useful in
      cardiovascular disease.

PMID- 11976252
TI  - Effect of retroactive intercessory prayer. Cautious approach is needed.

PMID- 11976253
TI  - Careless talk may cost lives in attributing adverse events to ADP receptor
      antagonists.

PMID- 11976254
TI  - Proper benchmark for drug prescribing needs to be found.

PMID- 11976255
TI  - Serum magnesium must also be known in profound hypokalaemia.

PMID- 11976256
TI  - Prisoners at Guantanamo Bay. American doctors can be trusted not to practise
      torture.

PMID- 11976257
TI  - Tour operators should tell clients about potential risks of adventure holidays.

PMID- 11976262
TI  - Differential contributions of nitric oxide synthase isoforms at hippocampal
      formation to negative feedback regulation of penile erection in the rat.
AB  - We established previously that a novel negative feedback mechanism for the
      regulation of penile erection, which is triggered by ascending sensory inputs
      initiated by tumescence of the penis, exists in the hippocampal formation (HF).
      This study further evaluated the participation of nitric oxide (NO) and the
      contribution of nitric oxide synthase (NOS) isoforms at the HF in this process.
      Adult, male Sprague-Dawley rats that were anaesthetized and maintained with
      chloral hydrate were used, and intracavernous pressure (ICP) recorded from the
      corpus cavernosum of the penis was employed as our experimental index for penile
      erection. Microinjection bilaterally of a NO donor, S-nitroso-N
      acetylpenicillamine (0.25 or 1 nmoles), or the NO precursor, L-arginine (1 or 5
      nmoles), into the hippocampal CA1 or CA3 subfield or dentate gyrus elicited a
      significant reduction in baseline ICP. Bilateral hippocampal application of a NO
      trapping agent, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
      (10 nmoles), significantly potentiated the elevation in ICP induced by
      intracavernous administration of papaverine (400 microg). Microinjection
      bilaterally into the HF of equimolar doses (0.5 or 2.5 pmoles) of two selective
      neuronal NOS inhibitors, 7-nitroindazole or N(omega)-propyl-L-arginine; or
      equimolar doses (50 or 250 pmoles) of two selective inducible NOS inhibitors,
      aminoguanidine or S-methylisothiourea, significantly enhanced the magnitude
      and/or duration of the papaverine-induced elevation in ICP. In contrast,
      hippocampal application of a potent endothelial NOS inhibitor, N5-(1-iminoethyl)
      L-ornithine (18 or 92 nmoles), was ineffective. Neither of these inhibitors,
      furthermore, affected baseline ICP. These results suggest that NO generated via
      both neuronal and inducible NOS at the HF may participate in negative feedback
      regulation of penile erection.

PMID- 11976263
TI  - Molecular and pharmacological characterization of genes encoding urotensin-II
      peptides and their cognate G-protein-coupled receptors from the mouse and monkey.
AB  - Urotensin-II (U-II) and its receptor (UT) represent novel therapeutic targets for
      management of a variety of cardiovascular diseases. To test such hypothesis, it
      will be necessary to develop experimental animal models for the manipulation of U
      II/UT receptor system. The goal of this study was to clone mouse and primate
      preproU-II and UT for pharmacological profiling. Monkey and mouse preproU-II
      genes were identified to encode 123 and 125 amino acids. Monkey and mouse UT
      receptors were 389, and 386 amino acids, respectively. Genomic organization of
      mouse genes showed that the preproU-II has four exons, while the UT receptor has
      one exon. Although initially viewed by many exclusively as cardiovascular
      targets, the present study demonstrates expression of mouse and monkey U-II/UT
      receptor mRNA in extra-vascular tissue including lung, pancreas, skeletal muscle,
      kidney and liver. Ligand binding studies showed that [125I]h U-II bound to a
      single sites to the cloned receptors in a saturable/high affinity manner (Kd
      654+/-154 and 214+/-65 pM and Bmax of 1011+/-125 and 497+/-68 fmol mg-1 for mouse
      and monkey UT receptors, respectively). Competition binding analysis demonstrated
      equipotent, high affinity binding of numerous mammalian, amphibian and piscine U
      II isopeptides to these receptors (Ki=0.8 - 3 nM). Fluorescein isothiocyanate
      (FITC) labelled U-II, bound specifically to HEK-293 cells expressing mouse or
      monkey UT receptor, confirming cell surface expression of recombinant UT
      receptor. Exposure of these cells to human U-II resulted in an increase in
      intracellular [Ca2+] concentrations (EC50 3.2+/-0.8 and 1.1+/-0.3 nM for mouse
      and monkey UT receptors, respectively) and inositol phosphate (Ip) formation
      (EC50 7.2+/-1.8 and 0.9+/-0.2 nM for mouse and monkey UT receptors, respectively)
      consistent with the primary signalling pathway for UT receptor involving
      phospholipase C activation.

PMID- 11976265
TI  - Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated protein
      in the pancreatic beta-cell.
AB  - Efaroxan induces membrane depolarization by interaction with the pore forming
      subunit of the ATP-sensitive potassium channel, Kir6.2. However, this effect is
      not responsible for its full secretory activity. In this study we have used an
      anti-idiotypic approach to generate antibodies that recognize additional proteins
      that may be regulated by efaroxan in pancreatic beta-cells. Using these antisera
      in an expression cloning strategy we have identified a monomeric GTP-binding
      protein, Rhes, as a potential target for regulation by imidazoline ligands. Rhes
      is shown to be expressed in beta-cells and its expression is regulated by
      efaroxan under conditions when a structurally related molecule, KU14R, is
      ineffective. The results reveal that beta-cells express Rhes and suggest that
      changes in the expression of this molecule may regulate the sensitivity of beta
      cells to imidazoline secretagogues.

PMID- 11976264
TI  - Regulation of human penile smooth muscle tone by prostanoid receptors.
AB  - We have characterized the prostanoid receptors involved in the regulation of
      human penile arterial and trabecular smooth muscle tone. Arachidonic acid induced
      relaxation of human corpus cavernosum strips (HCCS) that was blocked by the cyclo
      oxygenase inhibitor, indomethacin, and augmented by the thromboxane receptor (TP)
      antagonist, SQ29548, suggesting that endogenous production of prostanoids
      regulates penile smooth muscle tone. TP-receptors mediate contraction of HCCS and
      penile resistance arteries (HPRA), since the agonist of these receptors, U46619,
      potently contracted HCCS (EC50 8.3+/-2.8 nM) and HPRA (EC50 6.2+/-2.2 nM), and
      the contractions produced by prostaglandin F(2alpha) at high concentrations (EC50
      6460+/-3220 nM in HCCS and 8900+/-6700 nM in HPRA) were inhibited by the
      selective TP-receptor antagonist, SQ29548 (0.02 microM). EP-receptors are
      responsible for prostanoid-induced relaxant effects in HCCS because only
      prostaglandin E1 (PGE1), prostaglandin E2 and the EP2/EP4-receptor agonist,
      butaprost, produced consistent relaxation of this tissue (EC50 93.8+/-31.5,
      16.3+/-3.8 and 1820+/-1284 nM, respectively). In HPRA, both prostacyclin and PGE1
      (EC50 60.1+/-18.4 and 109.0+/-30.9 nM, respectively) as well as the selective IP
      receptor agonist, cicaprost, and butaprost (EC50 25.2+/-15.2 and 7050+/-6020 nM,
      respectively) caused relaxation, suggesting co-existence of IP- and EP-receptors
      (EP2 and/or EP4). In summary, endogenous production of prostanoids may regulate
      penile smooth muscle contractility by way of specific receptors. TP-receptors
      mediate contraction in HCCS and HPRA, while the relaxant effects of prostanoids
      are mediated by EP2- and/or EP4-receptors in HCCS and by EP- and IP-receptors in
      HPRA.

PMID- 11976266
TI  - The role of spinal neuropeptides and prostaglandins in opioid physical
      dependence.
AB  - This study examined the role of spinal calcitonin gene-related peptide (CGRP),
      substance P, and prostaglandins in the development and expression of opioid
      physical dependence. Administration of escalating doses (5 - 100 mg kg-1, i.p.)
      of morphine for 7 days markedly elevated CGRP and substance P- immunoreactivity
      in the dorsal horn of the rat spinal cord. Naloxone (2 mg kg-1, i.p.) challenge
      decreased both CGRP and substance P immunoreactivity and precipitated a robust
      withdrawal syndrome. Acute intrathecal pre-treatment with a CGRP receptor
      antagonist, CGRP(8 - 37) (4, 8 microg), a substance P receptor antagonist, SR
      140333 (1.4, 2.8 microg), a cyclo-oxygenase (COX) inhibitor, ketorolac (30, 45
      microg), and COX-2 selective inhibitors, DuP 697 (10, 30 microg) and nimesulide
      (30 microg), 30 min before naloxone challenge, partially attenuated the symptoms
      of morphine withdrawal. CGRP(8 - 37) (8 microg), but no other agents, inhibited
      the decrease in CGRP immunoreactivity. Chronic intrathecal treatment with CGRP(8 
      37) (4, 8 microg), SR 140333 (1.4 microg), ketorolac (15, 30 microg), DuP 697
      (10, 30micro g), and nimesulide (30 microg), delivered with daily morphine
      injection significantly attenuated both the symptoms of withdrawal and the
      decrease in CGRP but not substance P immunoreactivity. The results of this study
      suggest that activation of CGRP and substance P receptors, at the spinal level,
      contributes to the induction and expression of opioid physical dependence and
      that this activity may be partially expressed through the intermediary actions of
      prostaglandins.

PMID- 11976267
TI  - Effect of sodium nitroprusside and 8-bromo cyclic GMP on nerve-mediated and
      acetylcholine-evoked secretory responses in the rat pancreas.
AB  - The effects of sodium nitroprusside (SNP) and 8-bromo-guanosine 3'5' cyclic
      monophosphate (8-Br-cyclic GMP) on nerve-mediated and acetylcholine (ACh)-evoked
      amylase secretion, tritiated choline ([3H]-choline) release and on intracellular
      free calcium concentration ([Ca2+]i) in the isolated rat pancreas were
      investigated. Electrical field stimulation (EFS; 10 Hz) and ACh (1 x 10(-5) M)
      caused large increases in amylase output from pancreatic segments. The response
      to ACh was blocked by atropine (1 x 10(-5) M) whereas the EFS-evoked response was
      markedly reduced but not abolished. In contrast, pretreatment with tetrodotoxin
      (1 x 10(-6) M) abolished the secretory effect of EFS. Either SNP (1 x 10(-3) M)
      or 8-Br-cyclic GMP (1 x 10(-4) M) inhibited amylase secretion compared to basal.
      Combining either SNP or 8-Br-cyclic GMP with EFS resulted in a marked decrease in
      amylase output compared to EFS alone. In contrast, either SNP or 8-Br-cyclic GMP
      had no significant effect on the amylase response to ACh. When extracellular Ca2+
      concentration ([Ca2+]o) was elevated from 2.56 mM to 5.12 mM, SNP failed to
      inhibit the response to EFS. EFS stimulated the release of 3H from pancreatic
      segments preloaded with [3H]-choline. Either SNP or 8-Br-cyclic GMP had no effect
      on basal 3H release but significantly reduced the EFS-evoked response. In fura-2
      loaded acinar cells, SNP elicited a small decrease in [Ca2+]i compared to basal
      and had no effect on the ACh-induced [Ca2+]i peak response. Nitric oxide may
      modulate the release of endogenous neural ACh in response to EFS in the rat
      pancreas.

PMID- 11976268
TI  - Effect of low frequency electromagnetic fields on A2A adenosine receptors in
      human neutrophils.
AB  - The present study describes the effect of low frequency, low energy, pulsing
      electromagnetic fields (PEMFs) on A2A adenosine receptors in human neutrophils.
      Saturation experiments performed using a high affinity adenosine antagonist [3H]
      ZM 241385 revealed a single class of binding sites in control and in PEMF-treated
      human neutrophils with similar affinity (KD=1.05+/-0.10 and 1.08+/-0.12 nM,
      respectively). Furthermore, after 1 h of exposure to PEMFs the receptor density
      was statistically increased (P<0.01) (Bmax =126+/-10 and 215+/-15 fmol mg-1
      protein, respectively). The effect of PEMFs was specific to the A2A adenosine
      receptors. This effect was also intensity, time and temperature dependent. In the
      adenylyl cyclase assays the A2A receptor agonists, HE-NECA and NECA, increased
      cyclic AMP accumulation in untreated human neutrophils with an EC50 value of 43
      (40 - 47) and 255 (228 - 284) nM, respectively. The capability of HE-NECA and
      NECA to stimulate cyclic AMP levels in human neutrophils was increased (P<0.01)
      after exposure to PEMFs with an EC50 value of 10(8 - 13) and 61(52 - 71) nM,
      respectively. In the superoxide anion (O2-) production assays HE-NECA and NECA
      inhibited the generation of O2- in untreated human neutrophils, with an EC50
      value of 3.6(3.1 - 4.2) and of 23(20 - 27) nM, respectively. Moreover, in PEMF
      treated human neutrophils, the same compounds show an EC50 value of 1.6(1.2 -
      2.1) and of 6.0(4.7 - 7.5) nM respectively. These results indicate the presence
      of significant alterations in the expression and in the functionality of
      adenosine A2A receptors in human neutrophils treated with PEMFs.

PMID- 11976269
TI  - Effects of morphine and morphine withdrawal on brainstem neurons innervating
      hypothalamic nuclei that control the pituitary-adrenocortical axis in rats.
AB  - Different data support a role for brainstem noradrenergic inputs to the
      hypothalamic paraventricular nucleus (PVN) in the control of hypothalamus -
      pituitary - adrenocortical (HPA) axis. However, little is known regarding the
      functional adaptive changes of noradrenergic afferent innervating the PVN and
      supraoptic nucleus (SON) during chronic opioid exposure and upon morphine
      withdrawal. Here we have studied the expression of Fos after administration of
      morphine and during morphine withdrawal in the rat hypothalamic PVN and SON. Fos
      production was also studied in brainstem regions that innervate hypothalamic
      nuclei: the nucleus of solitary tract (NTS - A2) and the ventrolateral medulla
      (VLM - A1) and combined with immunostaining for tyrosine hydroxylase (TH) for
      immunohistochemical identification of active neurons during morphine withdrawal.
      Male rats were implanted with s.c. placebo or morphine (tolerant/dependent)
      pellets for 7 days. On day 8 rats received an injection of saline i.p., morphine
      i.p., saline s.c. or naloxone s.c. Acute morphine administration produced an
      increase in Fos expression at hypothalamic nuclei and in the brainstem regions,
      and tolerance developed towards this effect. Precipitated morphine withdrawal
      induced marked Fos immunoreactivity within the PVN and SON. Concomitantly,
      numerous neurons in the brainstem were stimulated by morphine withdrawal.
      Moreover, catecholaminergic-positive neurons in the brainstem showed a
      significant increase in Fos expression in response to morphine withdrawal. These
      findings demonstrate that chronic activation of opioid receptors results in
      altered patterns of immediate-early genes (IEG) expression in the PVN and SON,
      which occurs concurrently with an increased activity of their inputs from the
      brainstem.

PMID- 11976270
TI  - Mechanism of suppression of insulin signalling with lignocaine.
AB  - Lignocaine suppresses insulin-stimulated glucose transport into the cells and
      insulin-stimulated glycogenesis at doses equivalent to that used in the treatment
      of muscle pain disorder. We evaluated the direct effect of lignocaine on insulin
      receptor (IR) kinase activity. After lignocaine (40 mM, approximately equivalent
      to 1%) or an equal volume (100 microl) saline had been injected into the tibialis
      anterior muscle of rat, insulin (50 mM g-1 body weight) was administered into the
      portal vein in vivo. Immunoprecipitation and immunoblotting were used to detect
      insulin-mediated tyrosine phosphorylation of both IR-beta and insulin receptor
      substrate (IRS)-1, and insulin-stimulated binding of IRS-1 to p85 regulatory
      subunit of phosphatidylinositol 3-kinase (PI3-K) in the extracted muscle. In the
      in vitro study, purified IR from rat liver and/or recombinant IRS-1 protein with
      adenosine triphosphate were incubated with lignocaine (4 or 40 mM). Lignocaine
      reduced insulin-stimulated tyrosine phosphorylation of IR-beta to 12.6+/-5.7%
      (P<0.001), and IRS-1 to 32.1+/-18.8% (P<0.01), and also reduced insulin
      stimulated binding of IRS-1 to p85 to 27.4+/-12.7% (P<0.001) relative to control
      (100%) in muscle in vivo. The in vitro study revealed that lignocaine directly
      inhibited both basal and insulin-stimulated tyrosine phosphorylation of IR. These
      results indicate that clinically used doses of lignocaine inhibit insulin
      signalling in skeletal muscle. The inhibitory effect of lignocaine on tyrosine
      kinase activity of the IR underlies the suppression of insulin signalling with
      lignocaine.

PMID- 11976271
TI  - Dissociation of the PAF-receptor from NADPH oxidase and adenylate cyclase in
      human neutrophils results in accelerated influx and delayed clearance of
      cytosolic calcium.
AB  - The magnitude and duration of the abruptly occurring increases in cytosolic Ca2+
      in human neutrophils following activation with PAF (20 and 200 nM) and FMLP (1
      microM), have been compared and related to alterations in NADPH oxidase activity,
      membrane potential and intracellular cyclic AMP. Cytosolic Ca2+ and membrane
      potential were measured by spectrofluorimetry, transmembrane fluxes of Ca2+ by
      radiometric procedures, and NADPH oxidase activity and cyclic AMP by
      chemiluminescence and radioimmunoassay respectively. Activation of neutrophils
      with both PAF (200 nM) and FMLP (1 microM) was accompanied by an abrupt increase
      in cytosolic Ca2+, which was of similar magnitude for each activator (393+/-9 and
      378+/-17 nM respectively). Unlike FMLP-activated cells in which Ca2+ was rapidly
      removed from the cytosol, peak levels of cytosolic Ca2+ were sustained for longer
      (0.14+/-0.02 vs 1.16+/-0.04 min, P<or=0.0001) and declined at a slower rate in
      PAF-treated neutrophils. The prolonged elevation of cytosolic Ca2+ in PAF-treated
      cells was due to accelerated store-operated influx of extracellular cation and
      was attenuated by dibutyryl cyclic AMP (4 mM), the Ca2+-chelator, EGTA (5 mM),
      and SKF 96365 (10 microM). In contrast to FMLP, basal levels of superoxide
      production and cyclic AMP were unaltered in PAF-activated neutrophils, while only
      moderate membrane depolarization was detected. These observations demonstrate
      that mechanisms which restore Ca2+ homeostasis to FMLP-activated neutrophils,
      viz. activation of NADPH oxidase and adenylate cyclase, are not operative in PAF
      treated cells, presenting the potential hazard of Ca2+ overload and
      hyperactivity.

PMID- 11976272
TI  - Relaxation by urocortin of human saphenous veins.
AB  - Urocortin, an endogenous peptide structurally related to corticotropin-releasing
      factor (CRF), has potent cardiovascular effects, suggesting that it may be of
      significance in cardiovascular regulation. The objective of this study was to
      analyse the effects of urocortin and its action mechanisms on human blood
      vessels. To this, 3 mm long segments from human saphenous veins were prepared for
      isometric tension recording in an organ bath. In the segments at basal resting
      tone, urocortin did not produce any effect, but in the segments precontracted
      with endothelin-1 (1 - 10 nM), urocortin (1 pM - 10 nM) produced concentration
      dependent relaxation. This relaxation was not modified by the inhibitor of nitric
      oxide synthase NG-nitro-L-arginine methyl ester (L-NAME, 100 microM), but it was
      potentiated by the cyclo-oxygenase inhibitor meclofenamate (10 microM) and it was
      reduced by the inhibitors of high-conductance Ca2+-dependent potassium channels
      tetraethylammonium (TEA, 10 mM) and charybdotoxin (100 nM). These results
      indicate that human saphenous veins are very sensitive to urocortin, which
      produces vascular relaxation by a mechanism independent of nitric oxide and
      dependent of high-conductance Ca2+-dependent potassium channels, and that it may
      be opposed by the release of vasoconstrictor prostanoids. Therefore, urocortin
      may be of significance for regulation of the venous circulation in humans.

PMID- 11976273
TI  - Pharmacology of the nitric oxide receptor, soluble guanylyl cyclase, in
      cerebellar cells.
AB  - The nitric oxide (NO) receptor, soluble guanylyl cyclase (sGC), is commonly
      manipulated pharmacologically in two ways. Inhibition of activity is achieved
      using 1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one (ODQ) which oxidizes the haem
      prosthetic group to which NO binds, while the compound 3-(5-hydroxymethyl-2
      furyl)-1-benzylindazole (YC-1) is considered an 'allosteric' activator. Knowledge
      of how these agents function and interact in a normal cellular environment is
      limited. These issues were addressed using rat cerebellar cells. Inhibition by
      ODQ was not simply competitive with NO. The rate of onset was ODQ concentration
      dependent and developed in two kinetic phases. Recovery from inhibition occurred
      with a half-time of approximately 5 min. YC-1 slowed the rate at which sGC
      deactivated on removal of NO by 45 fold, consistent with YC-1 increasing the
      potency of NO for sGC. YC-1 also enhanced the maximal response to NO by 2 fold.
      Furthermore, when added to cells in which sGC was 90% desensitized, YC-1 abruptly
      enhanced sGC activity to a degree that indicated partial reversal of
      desensitization. After pre-exposure to YC-1, sGC became resistant to inhibition
      by ODQ. In addition, YC-1 rapidly reversed inhibition by ODQ in cells and for
      purified sGC, suggesting that YC-1 either increases the NO affinity of the
      oxidized sGC haem or reverses haem oxidation. It is concluded that the actions of
      ODQ and YC-1 on sGC are broadly similar in cells and purified preparations.
      Additionally, YC-1 transiently reverses sGC desensitization in cells. It is
      hypothesized that YC-1 has multiple actions on sGC, and thereby both modifies the
      NO binding site and enhances agonist efficacy.

PMID- 11976274
TI  - Oxygen-derived free radicals mediate endothelium-dependent contractions to
      acetylcholine in aortas from spontaneously hypertensive rats.
AB  - Experiments were designed to investigate whether or not oxygen-derived free
      radicals mediate endothelium-dependent contractions to acetylcholine in the aorta
      of spontaneously hypertensive rat (SHR). Isometric tension was measured in aortic
      rings taken from adult male SHR and Wistar-Kyoto rat (WKY) in the presence of NG
      nitro-L-arginine. Endothelium-dependent contractions to acetylcholine were
      significantly greater in rings from SHR compared to WKY. Oxygen-derived free
      radicals, generated from xanthine plus xanthine oxidase, induced contractions
      that were larger in aortas from SHR than from WKY. Contractions to acetylcholine
      and free radicals were abolished by a selective TP-receptor antagonist, S 18886,
      and a preferential inhibitor of cyclo-oxygenase-1, valeryl salicylate, but not by
      a preferential inhibitor of cyclo-oxygenase-2, NS-398. Allopurinol, deferoxamine
      and the combination of superoxide dismutase plus catalase inhibited the
      contractions to oxygen-derived free radicals but did not significantly affect
      those to acetylcholine. In contrast, diethyldithiocarbamic acid, an inhibitor of
      superoxide dismutase, or Tiron, a scavenger of superoxide anion, reduced
      endothelium-dependent contractions to acetylcholine in aortas from SHR. The
      effect of these two drugs was additive. In SHR chronically treated with
      dimethylthiourea endothelium-dependent contractions to acetylcholine were
      decreased, and reduced further by acute in vitro exposure to deferoxamine or the
      combination of superoxide dismutase plus catalase. These results suggest that in
      the SHR aorta acetylcholine-induced endothelium-dependent contractions involve
      endothelial superoxide anion production and the subsequent dismutation into
      hydroxyl radicals and/or hydrogen peroxide. The free radicals activate cyclo
      oxygenase-1, most likely to produce endoperoxides. Activation of TP-receptors is
      required to observe endothelium-dependent contractions to acetylcholine or
      endothelium-independent contractions in response to free radical generation.

PMID- 11976275
TI  - Airway hyperresponsiveness to adenosine induced by lipopolysaccharide in Brown
      Norway rats.
AB  - We have explored the effects of bacterial endotoxin (lipopolysaccharide; LPS) on
      the response of the airways of Brown Norway (BN) rats to adenosine. Comparisons
      have been drawn with the effects on responses to methacholine and 5
      hydroxytryptamine. In vehicle-challenged animals, adenosine, given i.v. was only
      a weak bronchoconstrictor. In contrast, 1 h following intratracheal
      administration of LPS, 0.3 mg kg-1, bronchoconstrictor responses to adenosine
      were markedly and selectively enhanced. At this time point, there were no
      significant changes in leukocyte numbers, eosinophil peroxidase and
      myeloperoxidase activities or protein concentrations in bronchoalveolar lavage
      (BAL) fluid. Twenty-four hours after challenge, the sensitivity of the airways to
      both adenosine and methacholine was reduced relative to the earlier time point
      and there were substantial increases in each marker of inflammation in BAL fluid.
      The bronchoconstrictor response to adenosine was blocked selectively by
      methysergide, disodium cromoglycate and the broad-spectrum adenosine receptor
      antagonist, 8-SPT, but not by DPCPX or ZM 243185, selective antagonists for the
      A1 and A2A receptors, respectively. Thus, the response to adenosine augmented
      following LPS is mast cell mediated and involves a receptor which can be blocked
      by 8-SPT but not by selective A1 or A2A receptor antagonists. It thus bears
      similarity to the augmented response to adenosine induced by allergen challenge
      in actively sensitized BN rats. Exposure to LPS could be a factor along with
      allergen in determining the increased sensitivity of the airways of asthmatics to
      adenosine.

PMID- 11976276
TI  - BIBN4096BS is a potent competitive antagonist of the relaxant effects of alpha
      CGRP on human temporal artery: comparison with CGRP(8-37).
AB  - Release of CGRP during migraine may produce harmful dilatation of cranial
      arteries, thereby possibly causing pain. We have compared the antagonism by
      BIBN4096BS and CGRP(8-37) of the relaxant effects of alpha-CGRP on rings of human
      temporal artery. alpha-CGRP relaxed the arteries precontracted with 9 - 24 mM KCl
      (-logEC50=9.4) nearly as efficaciously as sodium nitroprusside (10 microM).
      BIBN4096BS (0.1 - 100 nM) antagonized the effects of alpha-CGRP in surmountable
      manner with slopes of Schild-plots not different from unity. -LogKB values of
      10.1 and 10.4 were estimated for BIBN4096BS when administered before or during
      the KCl-contracture respectively. BIBN4096BS (1 microM) did not modify the
      relaxant effects of papaverine and sodium nitroprusside. CGRP(8-37) (1 - 10
      microM) antagonized the effects of alpha-CGRP in a surmountable manner with
      slopes of Schild-plots not different from unity. -LogKB values of 6.6 and 6.7
      were estimated for CGRP(8-37) administered before or during the KCl-contracture
      respectively. The high affinity of BIBN4096BS for CGRP receptors of human
      temporal artery makes it an excellent tool to explore the hypothesis of CGRP
      evoked cerebral vasodilation in migraine.

PMID- 11976277
TI  - Discrimination by SZL49 between contractions evoked by noradrenaline in
      longitudinal and circular muscle of human vas deferens.
AB  - The effects of irreversible alpha1-adrenoceptor antagonists, SZL-49 (an
      alkylating analogue of prazosin), dibenamine and benextramine on contractions to
      noradrenaline (NA) in longitudinal and circular muscle of human epididymal vas
      deferens were investigated. Competitive alpha1-adrenoceptor antagonists were also
      used to further characterize the alpha1-adrenoceptor subtype stimulated by NA in
      longitudinal and circular muscle. NA evoked concentration-dependent contractions
      of both muscle types (pD2; 5.4 and 5.2 respectively). The contraction of circular
      muscle was comparatively more sensitive than that of longitudinal muscle to
      pretreatment with SZL-49. In contrast, dibenamine or benextramine produced
      comparable effects in both muscle types. The relationship between receptor
      occupancy and contraction in either longitudinal or circular muscle was
      nonlinear, with half-maximal response requiring similar receptor occupancy
      (longitudinal muscle 14%, circular muscle 16%). Maximal response in both muscle
      types occurred with little or no receptor reserve (<10%). The competitive alpha1
      adrenoceptor antagonists produced dextral shifts of the dose-response curves to
      NA in longitudinal and circular muscle. The inhibitory potencies, estimated from
      the apparent pKB values were significantly different in longitudinal and circular
      muscle respectively for either WB 4101 (pKB, 8.6 and 9.5) or RS-17053 (pKB, 7.1
      and 9.0) but not for Rec 15/2739 (pKB, 9.2 and 9.8) or HV 723 (pKB, 8.3 and 8.4).
      In conclusion, the potency profile of the competitive alpha1-adrenoceptor
      antagonists and the lack of different receptor reserves for NA in the muscle
      types suggest that the discriminatory effects of SZL-49 is primarily due to a
      predominance of the alpha1L-adrenoceptor subtype in longitudinal muscle and
      alpha1A-subtype in circular muscle.

PMID- 11976278
TI  - Thioridazine interacts with the membrane of mitochondria acquiring antioxidant
      activity toward apoptosis--potentially implicated mechanisms.
AB  - We evaluated the effects of the phenothiazine derivative thioridazine on
      mechanisms of mitochondria potentially implicated in apoptosis, such as those
      involving reactive oxygen species (ROS) and cytochrome c release, as well as the
      involvement of drug interaction with mitochondrial membrane in these effects.
      Within the 0 - 100 microM range thioridazine did not reduce the free radical 1,1
      diphenyl-2-picryl-hydrazyl (DPPH) nor did it chelate iron. However, at 10 microM
      thioridazine showed important antioxidant activity on mitochondria, characterized
      by inhibition of accumulation of mitochondria-generated O2*-, assayed as
      lucigenin-derived chemiluminescence, inhibition of Fe2+/citrate-mediated lipid
      peroxidation of the mitochondrial membrane (LPO), assayed as malondialdehyde
      generation, and inhibition of Ca2+/t-butyl hydroperoxide (t-BOOH)-induced
      mitochondrial permeability transition (MPT)/protein-thiol oxidation, assayed as
      mitochondrial swelling. Thioridazine respectively increased and decreased the
      fluorescence responses of mitochondria labelled with 1-aniline-8-naphthalene
      sulfonate (ANS) and 1-(4-trimethylammonium phenyl)-6 phenyl 1,3,5-hexatriene (TMA
      DPH). The inhibition of LPO and MPT onset correlated well with the inhibition of
      cytochrome c release from mitochondria. We conclude that thioridazine interacts
      with the inner membrane of mitochondria, more likely close to its surface,
      acquiring antioxidant activity toward processes with potential implications in
      apoptosis such as O2*- accumulation, as well as LPO, MPT and associated release
      of cytochrome c.

PMID- 11976279
TI  - Atorvastatin inhibition of cytokine-inducible nitric oxide synthase expression in
      native endothelial cells in situ.
AB  - Animal experimental studies have demonstrated that inducible nitric oxide
      synthase (iNOS) expression correlates with neointima formation and is prevented
      by HMG-CoA reductase inhibitors (statins). In the present study we have
      investigated the underlying mechanism of action of these drugs in isolated
      segments of the rat aorta. Western blot analysis and immunohistochemistry
      revealed that tumour necrosis factor alpha (TNFalpha) plus interferon-gamma
      (IFNgamma) synergistically induce iNOS gene expression in the endothelium but not
      in the smooth muscle of these segments while constitutive endothelial NO synthase
      (eNOS) abundance was markedly reduced. Pre-treatment with 1 - 10 microM
      atorvastatin, cerivastatin or pravastatin decreased TNFalpha plus IFNgamma
      stimulated iNOS expression in the endothelium irrespective of the presence of the
      HMG-CoA reductase product mevalonate (400 microM). Electrophoretic mobility shift
      assay experiments confirmed that the combination of TNFalpha plus IFNgamma causes
      activation of the transcription factors STAT-1 and NF-kappaB in native
      endothelial cells. Neutralization of these transcription factors by employing the
      corresponding decoy oligonucleotides confirmed their involvement in TNFalpha plus
      IFNgamma stimulated iNOS expression. Translocation of both transcription factors
      was attenuated by atorvastatin, and this effect was insensitive to exogenous
      mevalonate. The present findings thus demonstrate a specific HMG-CoA reductase
      independent inhibitory effect of statins, namely atorvastatin, on cytokine
      stimulated transcription factor activation in native endothelial cells in situ
      and the subsequent expression of a gene product implicated in vascular
      inflammation. This effect may be therapeutically relevant and in addition provide
      an explanation for the reported rapid onset of action of these drugs in humans.

PMID- 11976280
TI  - Modulation of 5-HT4 receptor function in the rat isolated ileum by fluoxetine:
      the involvement of endogenous 5-hydroxytryptamine.
AB  - The effect of the selective serotonin reuptake inhibitor fluoxetine was examined
      on the 5-HT4 receptor-mediated relaxation in the rat isolated ileum. Fluoxetine
      unsurmountably antagonized the relaxation to exogenous 5-HT with abolition of the
      response at 10 microM. Fluoxetine (10 microM) also caused a gradual loss of the
      resting tension. These effects of fluoxetine were prevented by a prior addition
      of the 5-HT4 receptor selective antagonist GR113808 (100 nM), which itself caused
      a contraction of the tissues when administered alone. Fluoxetine (10 microM) also
      failed to prevent the relaxation due to exogenous 5-HT and the 5-HT4 receptor
      agonist 5-methoxytryptamine in tissues taken from the rats treated with para
      chlorophenylalanine (300 mg kg-1) for 3 and 6 days, which reduced the 5-HT level
      in the mucosa by 88 and 97.5% respectively. The contraction of the tissues with
      GR113808 indicates the presence of an endogenous 5-HT tone at the 5-HT4 receptor
      in the rat ileum. It is hypothesized that in the presence of fluoxetine, the
      concentration of endogenous 5-HT at the receptor was increased sufficiently to
      reduce or abolish the relaxation to 5-HT added exogenously. The inability of
      fluoxetine to prevent the relaxation to 5-HT in the presence of GR113808 or after
      the p-CPA treatment supports this hypothesis.

PMID- 11976283
TI  - Early activation of quorum sensing.

PMID- 11976284
TI  - Molecular genetics of bacteria and phages, 2001.

PMID- 11976286
TI  - Proteome and transcriptome analysis of the virulence genes regulated by the
      VirR/VirS system in Clostridium perfringens.
AB  - The proteins under the control of the two-component system VirR/VirS in
      Clostridium perfringens were analyzed by using two-dimensional gel
      electrophoresis of the culture supernatant from the wild type and the virR
      mutant. Based on matrix-assisted laser desorption ionization-time of flight/mass
      spectrometry, seven positively regulated proteins and eight negatively regulated
      proteins were identified. Transcriptome analysis confirmed that 7 of the 15
      proteins were regulated by the VirR/VirS system at the transcriptional level, but
      the remaining proteins were modified with a VirR/VirS-directed protease at the
      posttranslation and secretion levels. We purified and characterized the VirR/VirS
      directed protease from the culture supernatant and identified it as a kind of
      clostripain. Because this proteolytic activity was strongly inhibited by
      leupeptin and antipain, it was concluded that this protease was a member of the
      family of cysteine proteases of C. perfringens.

PMID- 11976285
TI  - Advancing the quorum in Pseudomonas aeruginosa: MvaT and the regulation of N
      acylhomoserine lactone production and virulence gene expression.
AB  - Pseudomonas aeruginosa regulates the production of many exoproteins and secondary
      metabolites via a hierarchical quorum-sensing cascade through LasR and RhlR and
      their cognate signal molecules N-(3-oxododecanoyl)-L-homoserine lactone (3O-C12
      HSL) and N-(butanoyl)-L-homoserine lactone (C4-HSL). In this study, we found that
      transcription of the quorum sensing-regulated genes lecA (coding for PA-IL
      lectin), lasB (coding for elastase), and rpoS appeared to be growth phase
      dependent and their expression could not be advanced to the logarithmic phase in
      cells growing in batch culture by the addition of exogenous C4-HSL and 3O-C12
      HSL. To identify novel regulators responsible for this growth phase dependency, a
      P. aeruginosa lecA::lux reporter strain was subjected to random transposon
      mutagenesis. A number of mutants affected in lecA expression were found that
      exhibited altered production of multiple quorum sensing-dependent phenotypes.
      While some mutations were mapped to new loci such as clpA and mvaT and a putative
      efflux system, a number of mutations were also mapped to known regulators such as
      lasR, rhlR, and rpoS. MvaT was identified as a novel global regulator of
      virulence gene expression, as a mutation in mvaT resulted in enhanced lecA
      expression and pyocyanin production. This mutant also showed altered swarming
      ability and production of the LasB and LasA proteases, 3O-C12-HSL, and C4-HSL.
      Furthermore, addition of exogenous 3O-C12-HSL and C4-HSL to the mvaT mutant
      significantly advanced lecA expression, suggesting that MvaT is involved in the
      growth phase-dependent regulation of the lecA gene.

PMID- 11976287
TI  - Proteolytic activity of YibP protein in Escherichia coli.
AB  - Escherichia coli YibP protein (47.4 kDa) has a membrane-spanning signal at the N
      terminal region, two long coiled-coil regions in the middle part, and a C
      terminal globular domain, which involves amino acid sequences homologous to the
      peptidase M23/M37 family. A yibP disrupted mutant grows in rich medium at 37
      degrees C but not at 42 degrees C. In the yibP null mutant, cell division and
      FtsZ ring formation are inhibited at 42 degrees C without SOS induction,
      resulting in filamentous cells with multiple nucleoids and finally in cell lysis.
      Five percent betaine suppresses the temperature sensitivity of the yibP disrupted
      mutation. The mutant has the same sensitivity to drugs, such as nalidixic acid,
      ethidium bromide, ethylmethane sulfonate, and sodium dodecyl sulfate, as the
      parental strain. YibP protein is recovered in the inner membrane and cytoplasmic
      fractions, but not in the outer membrane fraction. Results suggest that the
      coiled-coil regions and the C-terminal globular domain of YibP are localized in
      the cytoplasmic space, not in the periplasmic space. Purified YibP has a protease
      activity that split the substrate beta-casein.

PMID- 11976288
TI  - Functional characterization and regulation of gadX, a gene encoding an AraC/XylS
      like transcriptional activator of the Escherichia coli glutamic acid
      decarboxylase system.
AB  - The Escherichia coli chromosome contains two distantly located genes, gadA and
      gadB, which encode biochemically undistinguishable isoforms of glutamic acid
      decarboxylase (Gad). The Gad reaction contributes to pH homeostasis by consuming
      intracellular H(+) and producing gamma-aminobutyric acid. This compound is
      exported via the protein product of the gadC gene, which is cotranscribed with
      gadB. Here we demonstrate that transcription of both gadA and gadBC is positively
      controlled by gadX, a gene downstream of gadA, encoding a transcriptional
      regulator belonging to the AraC/XylS family. The gadX promoter encompasses the 67
      bp region preceding the gadX transcription start site and contains both RpoD and
      RpoS putative recognition sites. Transcription of gadX occurs in neutral rich
      medium upon entry into the stationary phase and is increased at acidic pH,
      paralleling the expression profile of the gad structural genes. However,
      P(T5)lacO-controlled gadX expression in neutral rich medium results in
      upregulation of target genes even in exponential phase, i.e., when the gad system
      is normally repressed. Autoregulation of the whole gad system is inferred by the
      positive effect of GadX on the gadA promoter and gadAX cotranscription.
      Transcription of gadX is derepressed in an hns mutant and strongly reduced in
      both rpoS and hns rpoS mutants, consistent with the expression profile of gad
      structural genes in these genetic backgrounds. Gel shift and DNase I footprinting
      analyses with a MalE-GadX fusion protein demonstrate that GadX binds gadA and
      gadBC promoters at different sites and with different binding affinities.

PMID- 11976289
TI  - The membrane-associated protein-serine/threonine kinase from Sulfolobus
      solfataricus is a glycoprotein.
AB  - Treatment of a sodium dodecyl sulfate-polyacrylamide gel with periodic acid
      Schiff (PAS) stain or blotting with Galanthus nivalis agglutinin revealed the
      presence of several glycosylated polypeptides in a partially purified detergent
      extract of the membrane fraction of Sulfolobus solfataricus. One of the
      glycoproteins comigrated with the membrane-associated protein-serine/threonine
      kinase from S. solfataricus, which had been radiolabeled by autophosphorylation
      with [(32)P]ATP in vitro. Treatment with a chemical deglycosylating agent,
      trifluoromethanesulfonic acid, abolished PAS staining and reduced the M(r) of the
      protein kinase from approximately 67,000 to approximately 62,000. Protein kinase
      activity also adhered to, and could be eluted from, agarose beads containing
      bound G. nivalis agglutinin. Glycosylation of the protein kinase implies that at
      least a portion of this integral membrane protein resides on the external surface
      of the cell membrane.

PMID- 11976290
TI  - The O-antigen gene cluster of Escherichia coli O55:H7 and identification of a new
      UDP-GlcNAc C4 epimerase gene.
AB  - Escherichia coli O55 is an important antigen which is often associated with
      enteropathogenic E. coli clones. We sequenced the genes responsible for its
      synthesis and identified genes for O-antigen polymerase, O-antigen flippase, four
      enzymes involved in GDP-colitose synthesis, and three glycosyltransferases, all
      by comparison with known genes. Upstream of the normal O-antigen region there is
      a gne gene, which encodes a UDP-GlcNAc epimerase for converting UDP-GlcNAc to UDP
      GalNAc and is essential for O55 antigen synthesis. The O55 gne product has only
      20 and 26% identity to the gne genes of Pseudomonas aeruginosa and E. coli O113,
      respectively. We also found evidence for the O55 gene cluster's having evolved
      from another gene cluster by gain and loss of genes. Only three of the GDP
      colitose pathway genes are in the usual location, the other two being separated,
      although nearby. It is thought that the E. coli O157:H7 clone evolved from the
      O55:H7 clone in part by transfer of the O157 gene cluster into an O55 lineage.
      Comparison of genes flanking the O-antigen gene clusters of the O55:H7 and
      O157:H7 clones revealed one recombination site within the galF gene and located
      the other between the hisG and amn genes. Genes outside the recombination sites
      are 99.6 to 100% identical in the two clones, while most genes thought to have
      transferred with the O157 gene cluster are 95 to 98% identical.

PMID- 11976291
TI  - The evolving genome of Salmonella enterica serovar Pullorum.
AB  - Salmonella enterica serovar Pullorum is a fowl-adapted bacterial pathogen that
      causes dysentery (pullorum disease). Host adaptation and special pathogenesis
      make S. enterica serovar Pullorum an exceptionally good system for studies of
      bacterial evolution and speciation, especially regarding pathogen-host
      interactions and the acquisition of pathogenicity. We constructed a genome map of
      S. enterica serovar Pullorum RKS5078, using I-CeuI, XbaI, AvrII, and SpeI and
      Tn10 insertions. Pulsed-field gel electrophoresis was employed to separate the
      large DNA fragments generated by the endonucleases. The genome is 4,930 kb, which
      is similar to most salmonellas. However, the genome of S. enterica serovar
      Pullorum RKS5078 is organized very differently from the majority of salmonellas,
      with three major inversions and one translocation. This extraordinary genome
      structure was seen in most S. enterica serovar Pullorum strains examined, with
      different structures in a minority of S. enterica serovar Pullorum strains. We
      describe the coexistence of different genome structures among the same bacteria
      as genomic plasticity. Through comparisons with S. enterica serovar Typhimurium,
      we resolved seven putative insertions and eight deletions ranging in size from 12
      to 157 kb. The genomic plasticity seen among S. enterica serovar Pullorum strains
      supported our hypothesis about its association with bacterial evolution: a large
      genomic insertion (157 kb in this case) disrupted the genomic balance, and
      rebalancing by independent recombination events in individual lineages resulted
      in diverse genome structures. As far as the structural plasticity exists, the S.
      enterica serovar Pullorum genome will continue evolving to reach a further
      streamlined and balanced structure.

PMID- 11976292
TI  - Using disulfide bond engineering to study conformational changes in the beta'260
      309 coiled-coil region of Escherichia coli RNA polymerase during sigma(70)
      binding.
AB  - RNA polymerase of Escherichia coli is the sole enzyme responsible for mRNA
      synthesis in the cell. Upon binding of a sigma factor, the holoenzyme can direct
      transcription from specific promoter sequences. We have previously defined a
      region of the beta' subunit (beta'260-309, amino acids 260 to 309) which adopts a
      coiled-coil conformation shown to interact with sigma(70) both in vitro and in
      vivo. However, it was not known if the coiled-coil conformation was maintained
      upon binding to sigma(70). In this work, we engineered a disulfide bond within
      beta'240-309 that locks the beta' coiled-coil region in the coiled-coil
      conformation, and we show that this "locked" peptide is able to bind to
      sigma(70). We also show that the locked coiled-coil is capable of inducing a
      conformational change within sigma(70) that allows recognition of the -10
      nontemplate strand of DNA. This suggests that the coiled-coil does not adopt a
      new conformation upon binding sigma(70) or upon recognition of the -10
      nontemplate strand of DNA.

PMID- 11976293
TI  - Functional analysis of the signal recognition particle in Escherichia coli by
      characterization of a temperature-sensitive ffh mutant.
AB  - The Ffh protein of Escherichia coli is a 48-kDa polypeptide that is homologous to
      the SRP54 subunit of the eukaryotic signal recognition particle (SRP). Efforts to
      understand the function of Ffh in bacteria have depended largely on the use of E.
      coli strains that allow depletion of the wild-type gene product. As an
      alternative approach to studying Ffh, a temperature-sensitive ffh mutant was
      isolated. The ffh-10(Ts) mutation results in two amino acid changes in conserved
      regions of the Ffh protein, and characterization of the mutant revealed that the
      cells rapidly lose viability at the nonpermissive temperature of 42 degrees C as
      well as show reduced growth at the permissive temperature of 30 degrees C. While
      the ffh mutant is defective in insertion of inner membrane proteins, the export
      of proteins with cleavable signal sequences is not impaired. The mutant also
      shows elevated expression of heat shock proteins and accumulates insoluble
      proteins, especially at 42 degrees C. It was further observed that the
      temperature sensitivity of the ffh mutant was suppressed by overproduction of
      4.5S RNA, the RNA component of the bacterial SRP, by stabilizing the thermolabile
      protein. Collectively, these results are consistent with a model in which Ffh is
      required only for localization of proteins integral to the cytoplasmic membrane
      and suggest new genetic approaches to the study of how the structure of the SRP
      contributes to its function.

PMID- 11976295
TI  - PehN, a polygalacturonase homologue with a low hydrolase activity, is coregulated
      with the other Erwinia chrysanthemi polygalacturonases.
AB  - Erwinia chrysanthemi 3937 secretes an arsenal of pectinolytic enzymes, including
      at least eight endo-pectate lyases encoded by pel genes, which play a major role
      in the soft-rot disease caused by this bacterium on various plants. E.
      chrysanthemi also produces some hydrolases that cleave pectin. Three adjacent
      hydrolase genes, pehV, pehW, and pehX, encoding exo-poly-alpha-D
      galacturonosidases, have been characterized. These enzymes liberate
      digalacturonides from the nonreducing end of pectin. We report the identification
      of a novel gene, named pehN, encoding a protein homologous to the glycosyl
      hydrolases of family 28, which includes mainly polygalacturonases. PehN has a low
      hydrolase activity on polygalacturonate and on various pectins. PehN action
      favors the activity of the secreted endo-pectate lyases, mainly PelB and PelC,
      and that of the periplasmic exo-pectate lyase PelX. However, removal of the pehN
      gene does not significantly alter the virulence of E. chrysanthemi. Regulation of
      pehN transcription was analyzed by using gene fusions. Like other pectinase
      genes, pehN transcription is dependent on several environmental conditions. It is
      induced by pectic catabolic products and is affected by growth phase, catabolite
      repression, osmolarity, anaerobiosis, nitrogen starvation, and the presence of
      calcium ions. The transcription of pehN is modulated by the repressor KdgR, which
      controls almost all the steps of pectin catabolism, and by cyclic AMP receptor
      protein (CRP), the global activator of sugar catabolism. The regulator PecS,
      which represses the transcription of the pel genes but activates that of pehV,
      pehW, and pehX, also activates transcription of pehN. The three regulators KdgR,
      PecS, and CRP act by direct interaction with the pehN promoter region. The
      sequences involved in the binding of these three regulators and of RNA polymerase
      have been precisely defined. Analysis of the simultaneous binding of these
      proteins indicates that CRP and RNA polymerase bind cooperatively and that the
      binding of KdgR could prevent pehN transcription. In contrast, the activator
      effect of PecS is not linked to competition with KdgR or to cooperation with CRP
      or RNA polymerase. This effect probably results from competition between PecS and
      an unidentified repressor involved in peh regulation.

PMID- 11976296
TI  - Escherichia coli DNA polymerase III can replicate efficiently past a T-T cis-syn
      cyclobutane dimer if DNA polymerase V and the 3' to 5' exonuclease proofreading
      function encoded by dnaQ are inactivated.
AB  - Although very little replication past a T-T cis-syn cyclobutane dimer normally
      takes place in Escherichia coli in the absence of DNA polymerase V (Pol V), we
      previously observed as much as half of the wild-type bypass frequency in Pol V
      deficient (DeltaumuDC) strains if the 3' to 5' exonuclease proofreading activity
      of the Pol III epsilon subunit was also disabled by mutD5. This observation might
      be explained in at least two ways. In the absence of Pol V, wild-type Pol III
      might bind preferentially to the blocked primer terminus but be incapable of
      bypass, whereas the proofreading-deficient enzyme might dissociate more readily,
      providing access to bypass polymerases. Alternatively, even though wild-type Pol
      III is generally regarded as being incapable of lesion bypass, proofreading
      impaired Pol III might itself perform this function. We have investigated this
      issue by examining dimer bypass frequencies in DeltaumuDC mutD5 strains that were
      also deficient for Pol I, Pol II, and Pol IV, both singly and in all
      combinations. Dimer bypass frequencies were not decreased in any of these strains
      and indeed in some were increased to levels approaching those found in strains
      containing Pol V. Efficient dimer bypass was, however, entirely dependent on the
      proofreading deficiency imparted by mutD5, indicating the surprising conclusion
      that bypass was probably performed by the mutD5 Pol III enzyme itself. This
      mutant polymerase does not replicate past the much more distorted T-T (6-4)
      photoadduct, however, suggesting that it may only replicate past lesions, like
      the T-T dimer, that form base pairs normally.

PMID- 11976294
TI  - BetS is a major glycine betaine/proline betaine transporter required for early
      osmotic adjustment in Sinorhizobium meliloti.
AB  - Hybridization to a PCR product derived from conserved betaine choline carnitine
      transporter (BCCT) sequences led to the identification of a 3.4-kb Sinorhizobium
      meliloti DNA segment encoding a protein (BetS) that displays significant sequence
      identities to the choline transporter BetT of Escherichia coli (34%) and to the
      glycine betaine transporter OpuD of Bacillus subtilis (30%). Although the BetS
      protein shows a common structure with BCCT systems, it possesses an unusually
      long hydrophilic C-terminal extension (169 amino acids). After heterologous
      expression of betS in E. coli mutant strain MKH13, which lacks choline, glycine
      betaine, and proline transport systems, both glycine betaine and proline betaine
      uptake were restored, but only in cells grown at high osmolarity or subjected to
      a sudden osmotic upshock. Competition experiments demonstrated that choline,
      ectoine, carnitine, and proline were not effective competitors for BetS-mediated
      betaine transport. Kinetic analysis revealed that BetS has a high affinity for
      betaines, with K(m)s of 16 +/- 2 microM and 56 +/- 6 microM for glycine betaine
      and proline betaine, respectively, in cells grown in minimal medium with 0.3 M
      NaCl. BetS activity appears to be Na(+) driven. In an S. meliloti betS mutant,
      glycine betaine and proline betaine uptake was reduced by about 60%, suggesting
      that BetS represents a major component of the overall betaine uptake activities
      in response to salt stress. beta-Galactosidase activities of a betS-lacZ strain
      grown in various conditions showed that betS is constitutively expressed. Osmotic
      upshock experiments performed with wild-type and betS mutant cells, treated or
      not with chloramphenicol, indicated that BetS-mediated betaine uptake is the
      consequence of immediate activation of existing proteins by high osmolarity, most
      likely through posttranslational activation. Growth experiments underscored the
      crucial role of BetS as an emerging system involved in the rapid acquisition of
      betaines by S. meliloti subjected to osmotic upshock.

PMID- 11976297
TI  - Mutational scanning and affinity cleavage analysis of UhpA-binding sites in the
      Escherichia coli uhpT promoter.
AB  - UhpA, a member of the NarL family of response regulators, activates transcription
      of the Escherichia coli uhpT gene for the sugar phosphate transporter UhpT in
      response to extracellular glucose-6-phosphate. UhpA binds with different
      affinities to adjacent regions in the uhpT promoter, termed the strong-binding
      (S) region from -80 to -50 and the weak-binding (W) region from -50 to -32.
      Transcription activation by UhpA is stimulated by the catabolite gene activator
      protein (CAP)-cyclic AMP complex and depends on the C-terminal domains of the RNA
      polymerase RpoA and RpoD subunits. Because single-base substitutions in the UhpA
      binding region had little effect on promoter activity, nucleotide substitutions
      in successive 4-bp blocks throughout this region were examined for their effects
      on promoter activation and UhpA binding. Changes in three of four blocks within
      the W region substantially impaired the ability of UhpA to bind to this region,
      to drive expression of a uhpT-lacZ reporter, and to support UhpA-dependent in
      vitro transcription. These W region variant promoters were strongly stimulated by
      CAP. Changes in several parts of the S region impaired UhpA binding to both the S
      and W regions and decreased promoter activity in vivo and in vitro. Thus, binding
      of UhpA to the W region is crucial for UhpA-dependent activation and depends on
      occupancy of the S region. None of these substitutions eliminated promoter
      function. The orientation of UhpA-binding sites was assessed by the affinity
      cleavage method. The iron chelate FeBABE [iron (S)-1-(p-bromoacetamidobenzyl)
      EDTA] was covalently attached to engineered cysteine residues near the DNA
      binding region in UhpA. Hydroxyl radicals generated by the iron chelate attached
      at position 187 resulted in DNA strand cleavages in two clusters of sites located
      in the middle of the S and W regions. These results are consistent with the
      binding of two dimers of UhpA. Each dimer binds to an inverted repeat of monomer
      binding sites with the consensus sequence CCTGRR, where R is A or G, and each is
      separated by 6 bp. It is likely that members of the NarL family bind to dyad
      targets, in contrast to the binding of OmpR family response regulators to direct
      repeat targets.

PMID- 11976298
TI  - Overexpression of two different GTPases rescues a null mutation in a heat-induced
      rRNA methyltransferase.
AB  - The Escherichia coli RrmJ (FtsJ) heat shock protein functions as an rRNA
      methyltransferase that modifies position U2552 of 23S rRNA in intact 50S
      ribosomal subunits. An in-frame deletion of the rrmJ (ftsJ) gene leads to severe
      growth disadvantages under all temperatures tested and causes significant
      accumulation of ribosomal subunits at the expense of functional 70S ribosomes. To
      investigate whether overexpression of other E. coli genes can restore the severe
      growth defect observed in rrmJ null mutants, we constructed an overexpression
      library from the rrmJ deletion strain and cloned and identified the E. coli genes
      that were capable of rescuing the rrmJ mutant phenotype. Our intention was to
      identify other methylases whose specificities overlapped enough with that of RrmJ
      to allow complementation when overexpressed. To our great surprise, no methylases
      were found by this method; rather, two small GTPases, Obg (YhbZ) and EngA, when
      overexpressed in the rrmJ deletion strains, were found to restore the otherwise
      severely impaired ribosome assembly process and/or stability of 70S ribosomes.
      50S ribosomal subunits prepared from these overexpressing strains were shown to
      still serve as in vitro substrates for purified RrmJ, indicating that the 23S
      rRNA likely was still lacking the highly conserved Um2552 modification. The
      apparent lack of this modification, however, no longer caused ribosome defects or
      a growth disadvantage. Massive overexpression of another related small GTPase,
      Era, failed to rescue the growth defects of an rrmJ strain. These findings
      suggest a hitherto unexpected connection between rRNA methylation and GTPase
      function, specifically that of the two small GTPases Obg and EngA.

PMID- 11976299
TI  - A quorum-sensing signaling system essential for genetic competence in
      Streptococcus mutans is involved in biofilm formation.
AB  - In a previous study, a quorum-sensing signaling system essential for genetic
      competence in Streptococcus mutans was identified, characterized, and found to
      function optimally in biofilms (Li et al., J. Bacteriol. 183:897-908, 2001).
      Here, we demonstrate that this system also plays a role in the ability of S.
      mutans to initiate biofilm formation. To test this hypothesis, S. mutans wild
      type strain NG8 and its knockout mutants defective in comC, comD, comE, and comX,
      as well as a comCDE deletion mutant, were assayed for their ability to initiate
      biofilm formation. The spatial distribution and architecture of the biofilms were
      examined by scanning electron microscopy and confocal scanning laser microscopy.
      The results showed that inactivation of any of the individual genes under study
      resulted in the formation of an abnormal biofilm. The comC mutant, unable to
      produce or secrete a competence-stimulating peptide (CSP), formed biofilms with
      altered architecture, whereas the comD and comE mutants, which were defective in
      sensing and responding to the CSP, formed biofilms with reduced biomass.
      Exogenous addition of the CSP and complementation with a plasmid containing the
      wild-type comC gene into the cultures restored the wild-type biofilm architecture
      of comC mutants but showed no effect on the comD, comE, or comX mutant biofilms.
      The fact that biofilms formed by comC mutants differed from the comD, comE, and
      comX mutant biofilms suggested that multiple signal transduction pathways were
      affected by CSP. Addition of synthetic CSP into the culture medium or
      introduction of the wild-type comC gene on a shuttle vector into the comCDE
      deletion mutant partially restored the wild-type biofilm architecture and further
      supported this idea. We conclude that the quorum-sensing signaling system
      essential for genetic competence in S. mutans is important for the formation of
      biofilms by this gram-positive organism.

PMID- 11976300
TI  - Caulobacter crescentus synthesizes an S-layer-editing metalloprotease possessing
      a domain sharing sequence similarity with its paracrystalline S-layer protein.
AB  - Strains of Caulobacter crescentus elaborate an S-layer, a two-dimensional protein
      latticework which covers the cell surface. The S-layer protein (RsaA) is secreted
      by a type I mechanism (relying on a C-terminal signal) and is unusual among type
      I secreted proteins because high levels of protein are produced continuously. In
      efforts to adapt the S-layer for display of foreign peptides and proteins, we
      noted a proteolytic activity that affected S-layer monomers with foreign inserts.
      The cleavage was precise, resulting in fragments with an unambiguous N-terminal
      sequence. We developed an assay to screen for loss of this activity (i.e.,
      presentation of foreign peptides without degradation), using transposon and
      traditional mutagenesis. A metalloprotease gene designated sap (S-layer
      associated protease) was identified which could complement the protease-negative
      mutants. The N-terminal half of Sap possessed significant similarity to other
      type I secreted proteases (e.g., alkaline protease of Pseudomonas aeruginosa),
      including the characteristic RTX repeat sequences, but the C-terminal half which
      normally includes the type I secretion signal exhibited no such similarity.
      Instead, there was a region of significant similarity to the N-terminal region of
      RsaA. We hypothesize that Sap evolved by combining the catalytic portion of a
      type I secreted protease with an S-layer-like protein, perhaps to associate with
      nascent S-layer monomers to "scan" for modifications.

PMID- 11976301
TI  - Rescue of social motility lost during evolution of Myxococcus xanthus in an
      asocial environment.
AB  - Replicate populations of the social bacterium Myxococcus xanthus underwent
      extensive evolutionary adaptation to an asocial selective environment (liquid
      batch culture). All 12 populations showed partial or complete loss of their
      social (S) motility function after 1,000 generations of evolution. Mutations in
      the pil gene cluster (responsible for type IV pilus biogenesis and function) were
      found to be at least partially responsible for the loss of S motility in the
      majority of evolved lines. Restoration (partial or complete) of S motility in the
      evolved lines by genetic complementation with wild-type pil genes positively
      affected their fruiting body development and sporulation while negatively
      affecting their competitive fitness in the asocial regime. This genetic tradeoff
      indicates that mutations in the pil region were adaptive in the asocial selective
      environment. This finding was confirmed by experiments showing that defined
      deletions of pil gene regions conferred a competitive advantage under asocial
      conditions. Moreover, an amino acid substitution in an evolved genotype was
      located in a region predicted by genetic complementation analysis to bear an
      adaptive mutation.

PMID- 11976302
TI  - Identification of two prpDBC gene clusters in Corynebacterium glutamicum and
      their involvement in propionate degradation via the 2-methylcitrate cycle.
AB  - Genome sequencing revealed that the Corynebacterium glutamicum genome contained,
      besides gltA, two additional citrate synthase homologous genes (prpC) located in
      two different prpDBC gene clusters, which were designated prpD1B1C1 and
      prpD2B2C2. The coding regions of the two gene clusters as well as the predicted
      gene products showed sequence identities of about 70 to 80%. Significant sequence
      similarities were found also to the prpBCDE operons of Escherichia coli and
      Salmonella enterica, which are known to encode enzymes of the propionate
      degrading 2-methylcitrate pathway. Homologous and heterologous overexpression of
      the C. glutamicum prpC1 and prpC2 genes revealed that their gene products were
      active as citrate synthases and 2-methylcitrate synthases. Growth tests showed
      that C. glutamicum used propionate as a single or partial carbon source, although
      the beginning of the exponential growth phase was strongly delayed by propionate
      for up to 7 days. Compared to growth on acetate, the specific 2-methylcitrate
      synthase activity increased about 50-fold when propionate was provided as the
      sole carbon source, suggesting that in C. glutamicum the oxidation of propionate
      to pyruvate occurred via the 2-methylcitrate pathway. Additionally, two
      dimensional gel electrophoresis experiments combined with mass spectrometry
      showed strong induction of the expression of the C. glutamicum prpD2B2C2 genes by
      propionate as an additional carbon source. Mutational analyses revealed that only
      the prpD2B2C2 genes were essential for the growth of C. glutamicum on propionate
      as a sole carbon source, while the function of the prpD1B1C1 genes remains
      obscure.

PMID- 11976303
TI  - An antisense RNA-mediated transcriptional attenuation mechanism functions in
      Escherichia coli.
AB  - Antisense RNA-mediated transcriptional attenuation is a regulatory mechanism
      operating in the replication control of two groups of plasmids in gram-positive
      bacteria, the pT181 group and the inc18 family, represented by pIP501. In
      contrast, this control mechanism has so far not been identified in gram-negative
      bacteria or their plasmids. In this work we asked whether such a mechanism can be
      supported by Escherichia coli. The core replication control regions of plasmids
      pT181 and pIP501 were transferred into this heterologous host. In vivo lacZ
      reporter gene assays showed that the antisense RNAs of these plasmids can inhibit
      lacZ expression and that most of this effect can be accounted for by reduced mRNA
      readthrough. Northern analyses confirmed that the ratio of attenuated to
      readthrough target RNA was increased in the presence of the cognate antisense
      RNA, as expected for this mechanism. Similarly, both antisense RNAs induced
      premature termination of their cognate target RNAs in an E. coli in vitro
      transcription system, whereas the noncognate antisense RNAs had no effect. Thus,
      this report shows that antisense RNA-mediated transcriptional attenuation is
      supported by at least one gram-negative host, although the data indicate that
      inhibitory efficiencies are lower than those for, e.g., Bacillus subtilis.
      Possible explanations for the apparent absence of this control mode in plasmids
      of gram-negative bacteria are discussed.

PMID- 11976304
TI  - Biological properties and cell tropism of Chp2, a bacteriophage of the obligate
      intracellular bacterium Chlamydophila abortus.
AB  - A number of bacteriophages belonging to the Microviridae have been described
      infecting chlamydiae. Phylogenetic studies divide the Chlamydiaceae into two
      distinct genera, Chlamydia and Chlamydophila, containing three and six different
      species, respectively. In this work we investigated the biological properties and
      host range of the recently described bacteriophage Chp2 that was originally
      discovered in Chlamydophila abortus. The obligate intracellular development cycle
      of chlamydiae has precluded the development of quantitative approaches to assay
      bacteriophage infectivity. Thus, we prepared hybridomas secreting monoclonal
      antibodies (monoclonal antibodies 40 and 55) that were specific for Chp2. We
      demonstrated that Chp2 binds both C. abortus elementary bodies and reticulate
      bodies in an enzyme-linked immunosorbent assay. Monoclonal antibodies 40 and 55
      also detected bacteriophage Chp2 antigens in chlamydia-infected eukaryotic cells.
      We used these monoclonal antibodies to monitor the ability of Chp2 to infect all
      nine species of chlamydiae. Chp2 does not infect members of the genus Chlamydia
      (C. trachomatis, C. suis, or C. muridarum). Chp2 can infect C. abortus, C. felis,
      and C. pecorum but is unable to infect other members of this genus, including C.
      caviae and C. pneumoniae, despite the fact that these chlamydial species support
      the replication of very closely related bacteriophages.

PMID- 11976306
TI  - Characterization of two cryptic Helicobacter pylori plasmids: a putative source
      for horizontal gene transfer and gene shuffling.
AB  - Many Helicobacter pylori isolates carry cryptic plasmids of extremely variable
      size. In this study we analyzed two H. pylori plasmids, pHel4 and pHel5, from H.
      pylori strains P8 and P29, respectively. Plasmid pHel4 consists of 10,970 bp,
      constituting 15 putative open reading frames (ORFs), whereas pHel5 consists of
      18,291 bp, constituting 17 ORFs. The findings that both plasmids encode a
      conserved RepA protein and that both have an origin of replication containing an
      iteron place them in the group of theta plasmids. In pHel4, the products of the
      overlapping orf4C, orf4D, orf4E, and orf4F sequences are homologous to MobA,
      MobB, MobC, and MobD, encoded by colicinogenic plasmids, suggesting that pHel4
      might be mobilizable. A further putative operon consists of orf4B and orf4A, the
      products of which are homologous to microcin C7 (MccC7) biosynthesis and
      secretion proteins MccB and MccC, respectively. Plasmid pHel5 carries putative
      genes encoding proteins with homology to an endonuclease and gene products of an
      H. pylori chromosomal plasticity zone. Both plasmids contain repeat sequences,
      such as the previously identified R2 repeat, which are considered preferred
      recombination sites. In pHel4, a new repeat sequence (R4 repeat), which seems to
      act as a hot spot for site-specific recombination, was identified. All H. pylori
      plasmids characterized so far have a modular structure. We suggest a model that
      explains the existing plasmids by insertions and deletions of genetic elements at
      the repeat sequences. A genetic exchange between plasmids and the bacterial
      chromosome, combined with plasmid mobilization, might add a novel mechanism to
      explain the high genetic macrodiversity within the H. pylori population.

PMID- 11976307
TI  - TraG-like proteins of DNA transfer systems and of the Helicobacter pylori type IV
      secretion system: inner membrane gate for exported substrates?
AB  - TraG-like proteins are potential NTP hydrolases (NTPases) that are essential for
      DNA transfer in bacterial conjugation. They are thought to mediate interactions
      between the DNA-processing (Dtr) and the mating pair formation (Mpf) systems.
      TraG-like proteins also function as essential components of type IV secretion
      systems of several bacterial pathogens such as Helicobacter pylori. Here we
      present the biochemical characterization of three members of the family of TraG
      like proteins, TraG (RP4), TraD (F), and HP0524 (H. pylori). These proteins were
      found to have a pronounced tendency to form oligomers and were shown to bind DNA
      without sequence specificity. Standard NTPase assays indicated that these TraG
      like proteins do not possess postulated NTP-hydrolyzing activity. Surface plasmon
      resonance was used to demonstrate an interaction between TraG and relaxase TraI
      of RP4. Topology analysis of TraG revealed that TraG is a transmembrane protein
      with cytosolic N and C termini and a short periplasmic domain close to the N
      terminus. We predict that multimeric inner membrane protein TraG forms a pore. A
      model suggesting that the relaxosome binds to the TraG pore via TraG-DNA and TraG
      TraI interactions is presented.

PMID- 11976308
TI  - The E1beta and E2 subunits of the Bacillus subtilis pyruvate dehydrogenase
      complex are involved in regulation of sporulation.
AB  - The pdhABCD operon of Bacillus subtilis encodes the pyruvate decarboxylase
      (E1alpha and E1beta), dihydrolipoamide acetyltransferase (E2), and
      dihydrolipoamide dehydrogenase (E3) subunits of the pyruvate dehydrogenase
      multienzyme complex (PDH). There are two promoters: one for the entire operon and
      an internal one in front of the pdhC gene. The latter may serve to ensure
      adequate quantities of the E2 and E3 subunits, which are needed in greater
      amounts than E1alpha and E1beta. Disruptions of the pdhB, pdhC, and pdhD genes
      were isolated, but attempts to construct a pdhA mutant were unsuccessful,
      suggesting that E1alpha is essential. The three mutants lacked PDH activity, were
      unable to grow on glucose and grew poorly in an enriched medium. The pdhB and
      pdhC mutants sporulated to only 5% of the wild-type level, whereas the pdhD
      mutant strain sporulated to 55% of the wild-type level. This difference indicated
      that the sporulation defect of the pdhB and pdhC mutant strains was due to a
      function(s) of these subunits independent of enzymatic activity. Growth, but not
      low sporulation, was enhanced by the addition of acetate, glutamate, succinate,
      and divalent cations. Results from the expression of various spo-lacZ fusions
      revealed that the pdhB mutant was defective in the late stages of engulfment or
      membrane fusion (stage II), whereas the pdhC mutant was blocked after the
      completion of engulfment (stage III). This analysis was confirmed by fluorescent
      membrane staining. The E1beta and E2 subunits which are present in the soluble
      fraction of sporulating cells appear to function independently of enzymatic
      activity as checkpoints for stage II-III of sporulation.

PMID- 11976310
TI  - AerR, a second aerobic repressor of photosynthesis gene expression in Rhodobacter
      capsulatus.
AB  - Open reading frame orf192, which is located immediately upstream of the aerobic
      repressor gene crtJ, was genetically and biochemically demonstrated to code for a
      second aerobic repressor (AerR) of photosynthesis gene expression in Rhodobacter
      capsulatus. Promoter-mapping studies indicate that crtJ has its own promoter but
      that a significant proportion of crtJ expression is promoted by read-through
      transcription of orf192 (aerR) transcripts through crtJ. Disruption of aerR
      resulted in increased photopigment biosynthesis during aerobic growth to a level
      similar to that of disruption of crtJ. Like that reported for CrtJ, beta
      galactosidase assays of reporter gene expression indicated that disruption of
      aerR resulted in a two- to threefold increase in aerobic expression of the crtI
      and pucB operons. However, unlike CrtJ, AerR aerobically represses puf operon
      expression and does not aerobically repress bchC expression. Gel mobility shift
      analysis with purified AerR indicates that AerR does not bind to a bchC promoter
      probe but does bind to the crtI, puc, and puf promoter probes. These results
      indicate that AerR is a DNA-binding protein that targets genes partially
      overlapping a subset of genes that are also controlled by CrtJ. We also provide
      evidence for cooperative binding of AerR and CrtJ to the puc promoter region.

PMID- 11976309
TI  - Snapshot of the genome of the pseudo-T-even bacteriophage RB49.
AB  - RB49 is a virulent bacteriophage that infects Escherichia coli. Its virion
      morphology is indistinguishable from the well-known T-even phage T4, but DNA
      hybridization indicated that it was phylogenetically distant from T4 and thus it
      was classified as a pseudo-T-even phage. To further characterize RB49, we
      randomly sequenced small fragments corresponding to about 20% of the
      approximately 170-kb genome. Most of these nucleotide sequences lacked sufficient
      homology to T4 to be detected in an NCBI BlastN analysis. However, when
      translated, about 70% of them encoded proteins with homology to T4 proteins.
      Among these sequences were the numerous components of the virion and the phage
      DNA replication apparatus. Mapping the RB49 genes revealed that many of them had
      the same relative order found in the T4 genome. The complete nucleotide sequence
      was determined for the two regions of RB49 genome that contain most of the genes
      involved in DNA replication. This sequencing revealed that RB49 has homologues of
      all the essential T4 replication genes, but, as expected, their sequences
      diverged considerably from their T4 homologues. Many of the nonessential T4 genes
      are absent from RB49 and have been replaced by unknown sequences. The intergenic
      sequences of RB49 are less conserved than the coding sequences, and in at least
      some cases, RB49 has evolved alternative regulatory strategies. For example, an
      analysis of transcription in RB49 revealed a simpler pattern of regulation than
      in T4, with only two, rather than three, classes of temporally controlled
      promoters. These results indicate that RB49 and T4 have diverged substantially
      from their last common ancestor. The different T4-type phages appear to contain a
      set of common genes that can be exploited differently, by means of plasticity in
      the regulatory sequences and the precise choice of a large group of facultative
      genes.

PMID- 11976311
TI  - Coordination of ubiquinol oxidase and cytochrome cbb(3) oxidase expression by
      multiple regulators in Rhodobacter capsulatus.
AB  - Rhodobacter capsulatus utilizes two terminal oxidases for aerobic respiration,
      cytochrome cbb(3) and ubiquinol oxidase. To determine the transcription factors
      involved in terminal oxidase expression, ccoN-lacZ and cydA-lacZ protein fusions
      were assayed in a variety of regulatory mutants. The results of this and previous
      studies indicate that cytochrome cbb(3) expression is controlled by regB-regA,
      fnrL, and hvrA and that ubiquinol oxidase expression is controlled by regB-regA,
      fnrL, hvrA, crtJ, and aerR.

PMID- 11976312
TI  - Effects of rodA and pbp2b disruption on cell morphology and oxidative stress
      response of Streptococcus thermophilus CNRZ368.
AB  - Insertional mutagenesis was used to isolate clones from Streptococcus
      thermophilus CNRZ368 that were modified in their abilities to tolerate oxidative
      stress. During this process, two menadione-sensitive clones (6G4 and 18C3) were
      found to display abnormal cell morphologies and distorted chain topologies and
      were further studied. Molecular characterization of both 6G4 and 18C3 mutants
      indicated that they were disrupted in open reading frames homologous to rodA and
      pbp2b, respectively. Both genes encoded proteins in Escherichia coli that were
      described as being implicated in peptidoglycan synthesis during the process of
      cell elongation and to function in determining the rod shape of the cell. This
      work reports a possible connection between peptidoglycan biosynthesis and
      oxidative stress defense in S. thermophilus CNRZ368.

PMID- 11976313
TI  - Elevated levels of ketopantoate hydroxymethyltransferase (PanB) lead to a
      physiologically significant coenzyme A elevation in Salmonella enterica serovar
      Typhimurium.
AB  - Pantothenate is the product of the ATP-dependent condensation of pantoate and
      beta-alanine and is a direct precursor of coenzyme A. A connection exists between
      pantothenate biosynthesis and thiamine biosynthesis in Salmonella enterica
      serovar Typhimurium since derivatives of a purF mutant that can grow (on glucose
      medium) in the absence of thiamine excrete pantothenate. We show here that the
      causative mutation in three such mutants was the addition of a CG base pair
      upstream of the panB gene. This base addition brings the spacing between the -10
      and -35 hexamers of the promoter to a consensus spacing of 17 bp and results in
      increased transcription of the pan operon. Furthermore, overexpression of PanB
      caused by this mutation, or by other means, was necessary and sufficient to
      increase pantothenate production and allow PurF-independent thiamine synthesis on
      glucose medium.

PMID- 11976314
TI  - Bacteriophage SP6 is closely related to phages K1-5, K5, and K1E but encodes a
      tail protein very similar to that of the distantly related P22.
AB  - The lytic salmonella phage SP6 encodes a tail protein with a high degree of
      sequence similarity to the tail protein of the biologically unrelated lysogenic
      salmonella phage P22. The SP6 tail gene is flanked by an upstream region that
      contains a promoter and a downstream region that contains a putative Rho
      independent transcription terminator, giving it a cassette or modular structure
      almost identical to the structure of the tail genes of coliphages K1E, K5, and K1
      5. It now appears that SP6, K1-5, K5, and K1E are very closely related but have
      different tail fiber proteins, giving them different host specificities.

PMID- 11976315
TI  - The secE gene of Helicobacter pylori.
AB  - Despite extensive annotation by two independent teams, the Helicobacter pylori
      genome appeared to lack a complete secretion machinery. The use of clinical
      isolates to substantiate in silico annotation is used here to identify the
      missing secE component of the major secretion machinery of Helicobacter pylori.

PMID- 11976316
TI  - Linear plasmid in the genome of Clavibacter michiganensis subsp. sepedonicus.
AB  - Contour-clamped homogeneous electric field gel analysis of genomic DNA of the
      plant pathogen Clavibacter michiganensis subsp. sepedonicus revealed the presence
      of a previously unreported extrachromosomal element. This new element was
      demonstrated to be a linear plasmid. Of 11 strains evaluated, all contained
      either a 90-kb (pCSL1) or a 140-kb (pCSL2) linear plasmid.

PMID- 11976317
TI  - Ribonuclease M5 has few, if any, mRNA substrates in Bacillus subtilis.
AB  - In Bacillus subtilis, maturation of 5S rRNA is catalyzed by an enzyme called
      RNase M5. We searched for potential mRNA substrates for RNase M5 by gene array
      technology, based on the premise that most endonucleolytic cleavages have an
      effect on the stability of RNA and hence on steady-state levels of expression.
      Only a handful of genes had significantly altered expression in rnmV mutants
      compared to wild-type strains that could subsequently be confirmed by Northern
      blotting. The effect of RNase M5 on the expression of the best candidates, the
      odhAB and sucCD operons, is indirect, by a mechanism we do not yet understand. We
      show that an effect of RNase M5 on the expression of the remaining candidate,
      ctsR, is due to the failure to process the 5S rRNA contained in the rrnW lying
      directly upstream. We thus conclude that RNase M5 has very few or possibly no
      mRNA substrates in B. subtilis.

PMID- 11976318
TI  - The RcsCB His-Asp phosphorelay system is essential to overcome chlorpromazine
      induced stress in Escherichia coli.
AB  - The RcsCB His-Asp phosphorelay system regulates the expression of several genes
      of Escherichia coli, but the molecular nature of the inducing signal is still
      unknown. We show here that treatment of an exponentially growing culture of E.
      coli with the cationic amphipathic compound chlorpromazine (CPZ) stimulates
      expression of a set of genes positively regulated by the RcsCB system. This
      induction is abolished in rcsB or rcsC mutant strains. In addition, treatment
      with CPZ inhibits growth. The wild-type strain is able to recover from this
      inhibition and resume growth after a period of adaptation. In contrast, strains
      deficient in the RcsCB His-Asp phosphorelay system are hypersensitive to CPZ.
      These results suggest that cells must express specific RcsCB-regulated genes in
      order to cope with the CPZ-induced stress. This is the first report of the
      essential role of the RcsCB system in a stress situation. These results also
      strengthen the notion that alterations of the cell envelope induce a signal
      recognized by the RcsC sensor.

PMID- 11976319
TI  - Identification of Aurora kinases as RasGAP Src homology 3 domain-binding
      proteins.
AB  - The GTPase-activating protein RasGAP functions as both a negative regulator and
      an effector of Ras proteins. In tumor cells, RasGAP is no longer able to
      deactivate oncogenic Ras proteins, and its effector function becomes predominant.
      As RasGAP itself has no obvious enzymatic function that may explain this effector
      function, we looked for downstream RasGAP effectors that could fulfill this role.
      We looked for the existence of RasGAP Src homology 3 (SH3) domain partners as
      this domain is involved in the regulation of cell proliferation and has an anti
      apoptotic effect. We report here the identification of a new RasGAP SH3 domain
      binding protein, named Aurora. This Drosophila melanogaster Ser/Thr kinase has
      three human orthologs called Aurora/Ipl1-related kinase or HsAIRK-1, -2, and -3.
      Coimmunoprecipitation experiments in COS cells confirmed that HsAIRK-1 and HsAIRK
      2 both interact with RasGAP. RasGAP pull-down experiments showed that it
      interacts with HsAIRK-1 in G(2)/M HeLa cells. We also demonstrated that RasGAP
      binds to the kinase domain of Aurora and that this interaction inhibits the
      kinase activity of HsAIRK-1 and HsAIRK-2. Finally we showed that RasGAP forms a
      ternary complex with HsAIRK and survivin. This complex may be involved in the
      regulation of the balance between cell division and apoptosis.

PMID- 11976320
TI  - Inhibition of interleukin-1beta -induced NF-kappa B activation by
      calcium/calmodulin-dependent protein kinase kinase occurs through Akt activation
      associated with interleukin-1 receptor-associated kinase phosphorylation and
      uncoupling of MyD88.
AB  - Calcium/calmodulin-dependent protein kinase kinase (CaMKK) and Akt are two
      multifunctional kinases involved in many cellular responses. Although Akt and
      Ca(2+) signals have been implicated in NF-kappaB activation in response to
      certain stimuli, these results are still controversial, and the mechanism(s)
      involved remains unknown. In this study, we show the roles that CaMKK and Akt
      play in regulating interleukin-1beta (IL-1beta)-induced NF-kappaB signaling. In
      human embryonic kidney 293 cells, IL-1beta induces IkappaB kinase beta (IKKbeta)
      activation, IkappaBalpha degradation, NF-kappaB transactivation, and weak Akt
      activation. A CaMKK inhibitor (KN-93) and phosphatidylinositol 3-kinase
      inhibitors (wortmannin and LY294002) do not inhibit IL-1beta-induced NF-kappaB
      activation. However, IL-1beta-induced NF-kappaB activity is attenuated by
      increased intracellular calcium in response to ionomycin, UTP, or thapsigargin or
      by overexpression of CaMKKc and/or Akt. Ionomycin and CaMKKc overexpression
      increases Akt phosphorylation on Thr(308) and enzyme activity. Under these
      conditions or upon overexpression of wild type Akt, IL-1beta-induced IKKbeta
      activity is diminished. Furthermore, a dominant negative mutant of Akt abolishes
      IKKbeta inhibition by CaMKKc and ionomycin, suggesting that Akt acts as a
      mediator of CaMKK signaling to inhibit IL-1beta-induced IKK activity at an
      upstream target site. We have also identified a novel interaction between CaMKK
      stimulated Akt and interleukin-1 receptor-associated kinase 1 (IRAK1), which
      plays a key role in IL-1beta-induced NF-kappaB activation. CaMKKc and Akt
      overexpression decreases IRAK1-mediated NF-kappaB activity and its association
      with MyD88 in response to IL-1beta stimulation. Furthermore, CaMKKc and Akt
      overexpression increases IRAK1 phosphorylation at Thr(100), and point mutation of
      this site abrogates the inhibitory effect of Akt on IRAK1-mediated NF-kappaB
      activation. Taken together, these results indicate a novel regulatory mechanism
      for IL-1beta signaling and suggest that CaMKK-dependent Akt activation inhibits
      IL-1beta-induced NF-kappaB activation through interference with the coupling of
      IRAK1 to MyD88.

PMID- 11976321
TI  - Substrate regulation of calcium binding in Ca2+-ATPase molecules of the
      sarcoplasmic reticulum. I. Effect of ATP.
AB  - The effect of ATP on calcium binding of the Ca2+-ATPase of the sarcoplasmic
      reticulum has not been clarified. By comparing the calcium dependence of the
      ATPase activity and of phosphorylation of the ATPase molecules with that of
      calcium binding in the absence of ATP, we show the existence of two types of
      regulatory site of the enzyme molecules at which ATP binding variously improves
      the calcium binding performance of the molecules depending on the aggregation
      state of the molecules and pH; the two regulatory sites bind ATP at submillimolar
      (0.25 mm) and millimolar (5 mm) ATP, respectively. The results are discussed
      based on a model of two conformational variants (A and B forms) of the chemically
      equivalent ATPase molecules (Nakamura, J., and Furukohri, T. (1994) J. Biol.
      Chem. 269, 30818-30821). For example, in the sarcoplasmic reticulum membrane at
      pH 7.40, submillimolar ATP converted the calcium binding manner of the A form
      from noncooperative (Hill number (n(H)) of approximately 1) to cooperative (n(H)
      approximately 2), concurrent with a decrease in the apparent calcium affinity
      (K(0.5)) from 2-6 to 0.1-0.3 microm. The binding of the A form became almost the
      same as that of the B form (n(H) approximately 2, K(0.5) approximately 0.2
      microm), which was not affected by ATP. Millimolar ATP further decreased the
      K(0.5) of the cooperative binding of the two forms to approximately 0.05 microm.
      Regulation of the calcium binding performance by ATP is discussed in terms of
      monomeric and oligomeric pathway models.

PMID- 11976322
TI  - Substrate regulation of calcium binding in Ca2+-ATPase molecules of the
      sarcoplasmic reticulum. II. Effect of CTP, GTP, ITP, and UTP.
AB  - To examine the effect of CTP, GTP, ITP, and UTP on calcium binding of Ca2+-ATPase
      molecules of the sarcoplasmic reticulum, the calcium dependence of the Ca2+
      activated hydrolysis activities of these NTPs of the enzyme molecules was
      examined by comparison with that of calcium binding of the molecules in the
      absence of the NTPs at pH 7.40. In the sarcoplasmic reticulum membrane, CTP, GTP,
      and ITP did not affect the noncooperative (Hill value (n(H)) of approximately 1,
      apparent calcium affinity (K(0.5)) of 2-6 microm)) and cooperative (n(H)
      approximately 2, K(0.5) approximately 0.2 microm) calcium binding of the
      molecules, whereas UTP caused the molecules to highly cooperatively (n(H)
      approximately 4) bind calcium ions with a lowered K(0.5) of approximately 0.04
      microm. When the enzyme molecules were solubilized with detergent, all of these
      NTPs reversibly degraded the calcium affinity of the molecule (from K(0.5) = 3-5
      to >40 microm), although the effect of the NTPs on the negatively cooperative
      manner (n(H) approximately 0.5) of calcium binding was not experimentally
      obtained. Taking into account the first part of this study (Nakamura, J., Tajima,
      G., Sato, C., Furukohri, T., and Konishi, K. (2002) J. Biol. Chem. 277, 24180
      24190) showing the improving effect of ATP on calcium binding of the membranous
      and solubilized molecules, the results show that ATP is the only intrinsic
      substrate for the enzyme molecule. This NTP regulation is discussed in terms of
      the oligomeric structure of the molecules.

PMID- 11976323
TI  - HPV-16 E6/7 immortalization sensitizes human keratinocytes to ultraviolet B by
      altering the pathway from caspase-8 to caspase-9-dependent apoptosis.
AB  - UVB from solar radiation is both an initiating and promoting agent for skin
      cancer. We have found that primary human keratinocytes undergo an apoptotic
      response to UVB. To determine whether these responses are altered during the
      course of immortalization, we examined markers of apoptosis in primary human
      foreskin keratinocytes (HFK) transduced with either a retroviral vector
      expressing the E6 and E7 genes of HPV-16 or with empty vector alone (LXSN-HFK).
      Whereas LXSN-HFK as well as early passage keratinocytes expressing HPV-16 E6 and
      E7 (p7 E6/7-HFK) were both moderately responsive to UVB irradiation, late passage
      immortalized keratinocytes (p27 E6/7-HFK) were exquisitely sensitive to UVB
      induced apoptosis. After exposure to UVB, enhanced annexin V-positivity and
      internucleosomal DNA fragmentation were observed in p27 E6/7-HFK compared with
      either LXSN- or p7 E6/7-HFK. Caspase-3 fluorometric activity assays as well as
      immunoblot analysis with antibodies to caspase-3 and poly(ADP-ribose) polymerase
      revealed elevated caspase-3 activity and processing at lower UVB doses in p27
      E6/7-HFK compared with LXSN- or p7 E6/7-HFK. In addition, the caspase inhibitor
      DEVD-CHO reduced the apoptotic response and increased survival of all three HFK
      types. Immunoblot analysis revealed that caspase-8 was activated in all three
      cell types, but caspase-9 was only activated in p27 E6/7-HFK. Cell cycle analysis
      further showed that only p27 E6/7-HFK exhibit G(2)/M accumulation that is
      enhanced by UVB treatment. This accumulation was associated with a rapid down
      regulation of Bcl-2 in these cells. The immortalization process subsequent to the
      expression of HPV E6 and E7 may therefore determine UVB sensitivity by switching
      the mode of apoptosis from a caspase-8 to a Bcl-2-caspase-9-mediated pathway of
      apoptosis.

PMID- 11976324
TI  - Spectroscopically and kinetically distinct conformational populations of sol-gel
      encapsulated carbonmonoxy myoglobin. A comparison with hemoglobin.
AB  - We have used sol-gel encapsulation protocols to trap kinetically and
      spectroscopically distinct conformational populations of native horse
      carbonmonoxy myoglobin. The method allows for direct comparison of functional and
      spectroscopic properties of equilibrium and non-equilibrium populations under the
      same temperature and viscosity conditions. The results implicate tertiary
      structure changes that include the proximal heme environment in the mechanism for
      population-specific differences in the observed rebinding kinetics. Differences
      in the resonance Raman frequency of nu(Fe-His), the iron-proximal histidine
      stretching mode, are attributed to differences in the positioning of the F helix.
      For myoglobin, the degree of separation between the F helix and the heme is
      assigned as the conformational coordinate that modulates both this frequency and
      the innermost barrier controlling CO rebinding. A comparison with the behavior of
      encapsulated derivatives of human adult hemoglobin indicates that these CO
      binding-induced conformational changes are qualitatively similar to the tertiary
      changes that occur within both the R and T quaternary states. Protein-specific
      differences in the time scale for the proposed F helix relaxation are attributed
      to variations in the intra-helical hydrogen bonding patterns that help stabilize
      the position of the F helix.

PMID- 11976325
TI  - Oxyopinins, large amphipathic peptides isolated from the venom of the wolf spider
      Oxyopes kitabensis with cytolytic properties and positive insecticidal
      cooperativity with spider neurotoxins.
AB  - Five amphipathic peptides with antimicrobial, hemolytic, and insecticidal
      activity were isolated from the crude venom of the wolf spider Oxyopes
      kitabensis. The peptides, named oxyopinins, are the largest linear cationic
      amphipathic peptides from the venom of a spider that have been chemically
      characterized at present. According to their primary structure Oxyopinin 1 is
      composed of 48 amino acid residues showing extended sequence similarity to the
      ant insecticidal peptide ponericinL2 and to the frog antimicrobial peptide
      dermaseptin. Oxyopinins 2a, 2b, 2c, and 2d have highly similar sequences. At
      least 27 out of 37 amino acid residues are conserved. They also show a segment of
      sequence similar to ponericinL2. Circular dichroism analyses showed that the
      secondary structure of the five peptides is essentially alpha-helical. Oxyopinins
      showed disrupting activities toward both biological membranes and artificial
      vesicles, particularly to those rich in phosphatidylcholine. Electrophysiological
      recordings performed on insect cells (Sf9) showed that the oxyopinins produce a
      drastic reduction of cell membrane resistance by opening non-selective ion
      channels. Additionally, a new paralytic neurotoxin named Oxytoxin 1 was purified
      from the same spider venom. It contains 69 amino acid residue cross-linked by
      five disulfide bridges. Application of mixtures containing oxyopinins and
      Oxytoxin 1 to insect larvae showed a potentiation phenomenon, by which an
      increase lethality effect is observed. These results suggest that the linear
      amphipathic peptides in spider venoms and neuropeptides cooperate to capture
      insects efficiently.

PMID- 11976326
TI  - CPG70 is a novel basic metallocarboxypeptidase with C-terminal polycystic kidney
      disease domains from Porphyromonas gingivalis.
AB  - In a search for a basic carboxypeptidase that might work in concert with the
      major virulence factors, the Arg- and Lys-specific cysteine endoproteinases of
      Porphyromonas gingivalis, a novel 69.8-kDa metallocarboxypeptidase CPG70 was
      purified to apparent homogeneity from the culture fluid of P. gingivalis HG66.
      Carboxypeptidase activity was measured by matrix-assisted laser desorption
      ionization-mass spectrometry using peptide substrates derived from a tryptic
      digest of hemoglobin. CPG70 exhibited activity with peptides containing C
      terminal Lys and Arg residues. The k(cat)/K(m) values for the hydrolysis of the
      synthetic dipeptides FA-Ala-Lys and FA-Ala-Arg by CPG70 were 99 and 56 mm(-1)s(
      1), respectively. The enzyme activity was strongly inhibited by the Arg analog (2
      guanidinoethylmercapto)succinic acid and 1,10-phenanthroline. High resolution
      inductively coupled plasma-mass spectrometry demonstrated that 1 mol of CPG70 was
      associated with 0.6 mol of zinc, 0.2 mol of nickel, and 0.2 mol of copper. A
      search of the P. gingivalis W83 genomic data base (TIGR) with the N-terminal
      amino acid sequence determined for CPG70 revealed that the enzyme is an N- and C
      terminally truncated form of a predicted 91.5-kDa protein (PG0232). Analysis of
      the deduced amino acid sequence of the full-length protein revealed an N-terminal
      signal sequence followed by a pro-segment, a metallocarboxypeptidase catalytic
      domain, three tandem polycystic kidney disease domains, and an 88-residue C
      terminal segment. The catalytic domain exhibited the highest sequence identity
      with the duck metallocarboxypeptidase D domain II. Insertional inactivation of
      the gene encoding CPG70 resulted in a P. gingivalis isogenic mutant that was
      avirulent in the murine lesion model under the conditions tested.

PMID- 11976327
TI  - Streptococcal Scl1 and Scl2 proteins form collagen-like triple helices.
AB  - The collagens are a family of animal proteins containing segments of repeated Gly
      Xaa-Yaa (GXY) motifs that form a characteristic triple-helical structure. Genes
      encoding proteins with repeated GXY motifs have also been reported in bacteria
      and phages; however, it is unclear whether these prokaryotic proteins can form a
      collagen-like triple-helical structure. Here we used two recently identified
      streptococcal proteins, Scl1 and Scl2, containing extended GXY sequence repeats
      as model proteins. First we observed that prior to heat denaturation recombinant
      Scl proteins migrated as homotrimers in gel electrophoresis with and without SDS.
      We next showed that the collagen-like domain of Scl is resistant to proteolysis
      by trypsin. We further showed that circular dichroism spectra of the Scl proteins
      contained features characteristic of collagen triple helices, including a
      positive maximum of ellipticity at 220 nm. Furthermore the triple helices of Scl1
      and Scl2 showed a temperature-dependent unfolding with melting temperatures of
      36.4 and 37.6 degrees C, respectively, which resembles those seen for collagens.
      We finally demonstrated by electron microscopy that the Scl proteins are
      organized into "lollipop-like" structures, similar to those seen in human
      proteins with collagenous domains. This implies that the repeated GXY tripeptide
      motif is a structural indicator of collagen-like triple helices in proteins from
      such phylogenetically distant sources as bacteria and humans.

PMID- 11976328
TI  - Geometric isomers of a photoactivable general anesthetic delineate a binding site
      on adenylate kinase.
AB  - General anesthetics are a class of drugs whose mode of action is poorly
      understood. Here, two photoactivable general anesthetics, n-octan-1-ol geometric
      isomers bearing a diazirine group on either the third or seventh carbon (3- and 7
      azioctanol, respectively), were used to locate and delineate an anesthetic site
      on adenylate kinase. Each photoincorporated at a mole ratio of 1:1 as determined
      by mass spectrometry. The photolabeled kinase was subjected to tryptic digest,
      and the fragments were separated by chromatography and sequenced by mass
      spectrometry. 3-Azioctanol photolabeled His-36, whereas its isomer, 7-azioctanol,
      photolabeled Asp-41. Inspection of the known structure of adenylate kinase shows
      that the side chains of these residues are within approximately 5 A of each
      other. This distance matches the separation of the 3- and 7-positions of an
      extended aliphatic chain. The alkanol site so-defined spans two domains of
      adenylate kinase. His-36 is part of the CORE domain, and Asp-41 belongs to the
      nucleotide monophosphate binding domain. Upon ligand binding the nucleotide
      monophosphate binding domain rotates relative to the CORE domain, causing a
      conformational change that might be expected to affect alkanol binding. Indeed,
      the substrate-mimicking inhibitor adenosine-(5')-pentaphospho-(5')-adenosine
      (Ap5A) reduced the photoincorporation of 3-[(3)H]azioctanol by 75%.

PMID- 11976329
TI  - The death domain of NF-kappa B1 p105 is essential for signal-induced p105
      proteolysis.
AB  - Stimulation of cells with tumor necrosis factor alpha (TNFalpha) triggers NF
      kappaB1 p105 proteolysis, releasing associated Rel subunits to translocate into
      the nucleus and modulate target gene expression. Phosphorylation of serine 927
      within the p105 PEST region by the IkappaB kinase (IKK) complex is required to
      promote p105 proteolysis in response to TNFalpha stimulation. In this study, the
      role of the p105 death domain (DD) in signal-induced p105 proteolysis is
      investigated. Endogenous p105 is shown to interact with the IKK complex in HeLa
      cells, and transient transfection experiments in 293 cells indicate that each of
      the catalytic components of the IKK complex, IKK1 and IKK2, can bind to p105.
      Interaction of p105 with both IKK1 and IKK2 is substantially reduced by deletion
      of the p105 DD or introduction of a specific point mutation (L841A) into the p105
      DD homologous to the lpr mutation in Fas. Phosphorylation of immunoprecipitated
      p105 on serine 927 by purified recombinant IKK1 or IKK2 protein in vitro is
      dramatically reduced in both DD mutants relative to wild type. Furthermore, both
      of the DD mutations significantly impair the ability of low concentrations of
      IKK2 to induce p105 serine 927 phosphorylation and proteolysis in transiently
      transfected 3T3 cells. However, high levels of transiently expressed IKK2 bypass
      the requirement for the p105 DD to induce p105 serine 927 phosphorylation.
      Finally, p105 serine 927 phosphorylation by the endogenous IKK complex after
      TNFalpha stimulation and subsequent p105 proteolysis is blocked in both p105 DD
      mutants when stably expressed in HeLa cells. Thus, the p105 DD acts as a docking
      site for IKK, increasing its local concentration in the vicinity of the p105 PEST
      region and facilitating efficient serine 927 phosphorylation.

PMID- 11976330
TI  - Smooth muscle myosin phosphatase-associated kinase induces Ca2+ sensitization via
      myosin phosphatase inhibition.
AB  - Smooth muscle calcium sensitization reflects an inhibition of myosin light chain
      phosphatase (SMPP-1m) activity; however, the underlying mechanisms are not well
      understood. SMPP-1m activity can be modulated through phosphorylation of the
      myosin targeting subunit (MYPT1) by the endogenous myosin phosphatase-associated
      kinase, MYPT1 kinase (MacDonald, J. A., Borman, M. A., Muranyi, A., Somlyo, A.
      V., Hartshorne, D. J., and Haystead, T. A. (2001) Proc. Natl. Acad. Sci. U. S. A.
      98, 2419-2424). Recombinant chicken gizzard MYPT1 (M130) was phosphorylated in
      vitro by a recombinant MYPT1 kinase, and the sites of phosphorylation were
      identified as Thr(654), Ser(808), and Thr(675). Introduction of recombinant MYPT1
      kinase elicited a calcium-independent contraction in beta-escin-permeabilized
      rabbit ileal smooth muscle. Using an antibody that specifically recognizes MYPT1
      phosphorylated at Thr(654) (M130 numbering), we determined that this calcium
      independent contraction was correlated with an increase in MYPT1 phosphorylation.
      These results indicate that SMPP-1m phosphorylation by MYPT1 kinase is a
      mechanism of smooth muscle calcium sensitization.

PMID- 11976331
TI  - Processing of an apicoplast leader sequence in Plasmodium falciparum and the
      identification of a putative leader cleavage enzyme.
AB  - The plastid (apicoplast) of the malaria-causing parasite Plasmodium falciparum
      was derived via a secondary endosymbiotic process. As in other secondary
      endosymbionts, numerous genes for apicoplast proteins are located in the nucleus,
      and the encoded proteins are targeted to the organelle courtesy of a bipartite N
      terminal extension. The first part of this leader sequence is a signal peptide
      that targets proteins to the secretory pathway. The second, so-called transit
      peptide region is required to direct proteins from the secretory pathway across
      the multiple membranes surrounding the apicoplast. In this paper we perform a
      pulse-chase experiment and N-terminal sequencing to show that the transit peptide
      of an apicoplast-targeted protein is cleaved, presumably upon import of the
      protein into the apicoplast. We identify a gene whose product likely performs
      this cleavage reaction, namely a stromal-processing peptidase (SPP) homologue. In
      plants SPP cleaves the transit peptides of plastid-targeted proteins. The P.
      falciparum SPP homologue contains a bipartite N-terminal apicoplast-targeting
      leader. Interestingly, it shares this leader sequence with a Delta-aminolevulinic
      acid dehydratase homologue via an alternative splicing event.

PMID- 11976332
TI  - Cloning and characterization of a low molecular weight prolyl 4-hydroxylase from
      Arabidopsis thaliana. Effective hydroxylation of proline-rich, collagen-like, and
      hypoxia-inducible transcription factor alpha-like peptides.
AB  - 4-Hydroxyproline is found in collagens and collagen-like proteins in animals and
      in many glycoproteins in plants. Animal prolyl 4-hydroxylases (P4Hs) have been
      cloned and characterized from many sources, but no plant P4H has been cloned so
      far. We report here that the genome of Arabidopsis thaliana encodes six P4H-like
      polypeptides, one of which, a 283-residue soluble monomer, was cloned and
      characterized here as a recombinant protein. Catalytically critical residues
      identified in animal P4Hs are conserved in this P4H, and their mutagenesis led to
      complete or almost complete inactivation. The recombinant P4H effectively
      hydroxylated poly(l-proline) and many synthetic peptides corresponding to proline
      rich repeats present in plant glycoproteins and other proteins. Surprisingly,
      collagen-like peptides were also good substrates, the V(max) with (Pro-Pro
      Gly)(10) being similar to that with poly(l-proline). The enzyme acted in this
      peptide preferentially on prolines in Y positions in the X-Y-Gly triplets.
      Correspondingly, (Gly-Pro-4Hyp)(5) and (Pro-Ala-Gly)(5) were poor substrates,
      with V(max) values less than 5 and 20% of that obtained with (Pro-Pro-Gly)(10),
      respectively, the K(m) for the latter also being high. Peptides representing the
      N- and C-terminal hydroxylation sites present in hypoxia-inducible transcription
      factor alpha also served as substrates. As these peptides contain only one
      proline residue, a poly(l-proline) type II conformation was clearly not required
      for hydroxylation.

PMID- 11976333
TI  - Galpha12 and Galpha13 negatively regulate the adhesive functions of cadherin.
AB  - Cadherins function to promote adhesion between adjacent cells and play critical
      roles in such cellular processes as development, tissue maintenance, and tumor
      suppression. We previously demonstrated that heterotrimeric G proteins of the G12
      subfamily comprised of Galpha12 and Galpha13 interact with the cytoplasmic domain
      of cadherins and cause the release of the transcriptional activator beta-catenin
      (Meigs, T. E., Fields, T. A., McKee, D. D., and Casey, P. J. (2001) Proc. Natl.
      Acad. Sci. U. S. A. 98, 519-524). Because of the importance of beta-catenin in
      cadherin-mediated cell-cell adhesion, we examined whether G12 subfamily proteins
      could also regulate cadherin function. The introduction of mutationally activated
      G12 proteins into K562 cells expressing E-cadherin blocked cadherin-mediated cell
      adhesion in steady-state assays. Also, in breast cancer cells, the introduction
      of activated G12 proteins blocked E-cadherin function in a fast aggregation
      assay. Aggregation mediated by a mutant cadherin that lacks G12 binding ability
      was not affected by activated G12 proteins, indicating a requirement for direct
      G12-cadherin interaction. Furthermore, in wound-filling assays in which ectopic
      expression of E-cadherin inhibits cell migration, the expression of activated G12
      proteins reversed the inhibition via a mechanism that was independent of G12
      mediated Rho activation. These results validate the G12-cadherin interaction as a
      potentially important event in cell biology and suggest novel roles for G12
      proteins in the regulation of cadherin-mediated developmental events and in the
      loss of cadherin function that is characteristic of metastatic tumor progression.

PMID- 11976334
TI  - Critical residues for structure and catalysis in short-chain
      dehydrogenases/reductases.
AB  - Short-chain dehydrogenases/reductases form a large, evolutionarily old family of
      NAD(P)(H)-dependent enzymes with over 60 genes found in the human genome. Despite
      low levels of sequence identity (often 10-30%), the three-dimensional structures
      display a highly similar alpha/beta folding pattern. We have analyzed the role of
      several conserved residues regarding folding, stability, steady-state kinetics,
      and coenzyme binding using bacterial 3beta/17beta-hydroxysteroid dehydrogenase
      and selected mutants. Structure determination of the wild-type enzyme at 1.2-A
      resolution by x-ray crystallography and docking analysis was used to interpret
      the biochemical data. Enzyme kinetic data from mutagenetic replacements emphasize
      the critical role of residues Thr-12, Asp-60, Asn-86, Asn-87, and Ala-88 in
      coenzyme binding and catalysis. The data also demonstrate essential interactions
      of Asn-111 with active site residues. A general role of its side chain
      interactions for maintenance of the active site configuration to build up a
      proton relay system is proposed. This extends the previously recognized catalytic
      triad of Ser-Tyr-Lys residues to form a tetrad of Asn-Ser-Tyr-Lys in the majority
      of characterized short-chain dehydrogenases/reductase enzymes.

PMID- 11976335
TI  - Hypercholesterolemia promotes a CD36-dependent and endothelial nitric-oxide
      synthase-mediated vascular dysfunction.
AB  - Numerous studies have implicated either the presence or absence of CD36 in the
      development of hypertension. In addition, hypercholesterolemia is associated with
      the loss of nitric oxide-induced vasodilation and the subsequent increase in
      blood pressure. In the current study, we tested the hypothesis that diet-induced
      hypercholesterolemia promotes the disruption of agonist-stimulated nitric oxide
      generation and vasodilation in a CD36-dependent manner. To test this, C57BL/6,
      apoE null, CD36 null, and apoE/CD36 null mice were maintained on chow or high fat
      diets. In contrast to apoE null mice fed a chow diet, apoE null mice fed a high
      fat diet did not respond to acetylcholine with a decrease in blood pressure.
      Caveolae isolated from in vivo vessels did not contain endothelial nitric-oxide
      synthase and were depleted of cholesterol. Age-matched apoE/CD36 null mice fed a
      chow or high fat diet responded to acetylcholine with a decrease in blood
      pressure. The mechanism underlying the vascular dysfunction was reversible
      because vessels isolated from apoE null high fat-fed mice regained responsiveness
      to acetylcholine when incubated with plasma obtained from chow-fed mice. Further
      analysis demonstrated that the plasma low density lipoprotein fraction was
      responsible for depleting caveolae of cholesterol, removing endothelial nitric
      oxide synthase from caveolae, and preventing nitric oxide production. In
      addition, the pharmacological removal of caveola cholesterol with cyclodextrin
      mimicked the effects caused by the low density lipoprotein fraction. We conclude
      that the ablation of CD36 prevented the negative impact of hypercholesterolemia
      on agonist-stimulated nitric oxide-mediated vasodilation in apoE null mice. These
      studies provide a direct link between CD36 and the early events that underlie
      hypercholesterolemia-mediated hypertension and mechanistic linkages between CD36
      function, nitric-oxide synthase activation, caveolae integrity, and blood
      pressure regulation.

PMID- 11976336
TI  - Convergence of signaling pathways on the activation of ERK in B cells.
AB  - The B cell receptor (BCR) initiates three major signaling pathways: the Ras
      pathway, which leads to extracellular signal-regulated kinase (ERK) activation;
      the phospholipase C-gamma pathway, which causes calcium mobilization; and the
      phosphoinositide 3-kinase (PI 3-kinase) pathway. These combine to induce
      different biological responses depending on the context of the BCR signal. Both
      the Ras and PI 3-kinase pathways are important for B cell development and
      activation. Several model systems show evidence of cross-regulation between these
      pathways. Here we demonstrate through the use of PI 3-kinase inhibitors and a
      dominant-negative PI 3-kinase construct that the BCR-induced phosphorylation and
      activation of ERK is dependent on PI 3-kinase. PI 3-kinase feeds into the Ras
      signaling cascade at multiple points, both upstream and downstream of Ras. We
      also show that ERK activation is dependent on phospholipase C-gamma, in keeping
      with its dependence on calcium mobilization. Last, the activation of PI 3-kinase
      itself is completely dependent on Ras. We conclude that the PI 3-kinase and Ras
      signaling cascades are intimately connected in B cells and that the activation of
      ERK is a signal integration point, since it requires simultaneous input from all
      three major signaling pathways.

PMID- 11976337
TI  - A 5-HT4 receptor transmembrane network implicated in the activity of inverse
      agonists but not agonists.
AB  - Activation of G protein-coupled receptors is thought to involve disruption of
      intramolecular interactions that stabilize their inactive conformation. Such
      disruptions are induced by agonists or by constitutively active mutations. In the
      present study, novel potent inverse agonists are described to inhibit the
      constitutive activity of 5-HT(4) receptors. Using these compounds and specific
      receptor mutations, we investigated the mechanisms by which inverse agonists may
      reverse the disruption of intramolecular interactions that causes constitutive
      activation. Two mutations (D100(3.32)A in transmembrane domain (TMD)-III and
      F275(6.51)A in TMD-VI) were found to completely block inverse agonist effects
      without impairing their binding properties nor the molecular activation switches
      induced by agonists. Based on the rhodopsin model, we propose that these mutated
      receptors are in equilibrium between two states R and R* but are unable to reach
      a third "silent" state stabilized by inverse agonists. We also found another
      mutation in TMD-VI (W272(6.48)A) that stabilized this silent state. This mutant
      remained fully activated by agonists. Molecular modeling indicated that Asp-100,
      Phe-275, and Trp-272 might constitute a network required for stabilization of the
      silent state by the described inverse agonists. However, this network is not
      necessary for agonist activity.

PMID- 11976338
TI  - Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers
      lipopolysaccharide responsiveness.
AB  - In order to mediate cellular response to lipopolysaccharide (LPS), Toll-like
      receptor (TLR) 4 must interact with MD-2, a secreted protein. In this study, a
      biochemical assay was developed to demonstrate that recombinant MD-2 can interact
      with the extracellular portion of TLR4 in solution. The ability of MD-2 to
      multimerize was confirmed, and MD-1 was also shown to possess this ability.
      Through site-directed mutagenesis, more than two intermolecular disulfide bonds
      were found to stabilize the MD-2 multimer. MD-2's abilities to confer LPS
      responsiveness and to bind TLR4 were strongly associated functions. Remarkably,
      although the majority of recombinant MD-2 exists in multimeric form, monomeric MD
      2 was found to preferentially bind TLR4 and to confer LPS responsiveness more
      efficiently than MD-2 multimers.

PMID- 11976339
TI  - The location of plastocyanin in vascular plant photosystem I.
AB  - We have studied the binding sites of the electron donor and acceptor proteins of
      vascular plant photosystem I by electron microscopy/crystallography. Previously,
      we identified the binding site for the electron acceptor (ferredoxin). In this
      paper we complete these studies with the characterization of the electron donor
      (plastocyanin) binding site. After cross-linking, plastocyanin is detected using
      Fourier difference analysis of two dimensionally ordered arrays of photosystem I
      located at the periphery of chloroplast grana. Plastocyanin binds in a small
      cavity on the lumenal surface of photosystem I, close to the center and with a
      slight bias toward the PsaL subunit of the complex. The recent release of the
      full coordinates for the cyanobacterial photosystem I reaction center has allowed
      a detailed comparison between the structures of the eukaryotic and prokaryotic
      systems. This reveals a very close homology, which is particularly striking for
      the lumenal side of photosystem I.

PMID- 11976340
TI  - The ATPase activity and the functional domain of PotA, a component of the
      sermidine-preferential uptake system in Escherichia coli.
AB  - The ATPase activity of PotA, a component of the spermidine-preferential uptake
      system consisting of PotA, -B, -C, and -D, was studied using purified PotA and a
      PotABC complex on inside-out membrane vesicles. It was found that PotA can form a
      dimer by disulfide cross-linking but that each PotA molecule functions
      independently. When PotA was associated with the membrane proteins PotB and PotC,
      the K(m) value for ATP increased and PotA became much more sensitive to
      inhibition by spermidine. It was also shown that spermidine uptake in cells was
      gradually inhibited in parallel with spermidine accumulation in cells. The
      results suggest that spermidine functions as a feedback inhibitor of spermidine
      transport. The function of PotA was analyzed using PotA mutants obtained by
      random mutagenesis. There are two domains in PotA. The NH2-terminal domain
      (residues 1-250) contains the ATP binding pocket formed in part by residues
      Cys26, Phe27, Phe45, Cys54, Leu60, and Leu76, the active center of ATPase that
      includes Val135 and Asp172, and amino acid residues necessary for the interaction
      with a second PotA subunit (Cys26) and with PotB (Cys54). The COOH-terminal
      domain (residues 251-378) of PotA contains a site that regulates ATPase activity
      and a site involved in the spermidine inhibition of ATPase activity.

PMID- 11976341
TI  - Activation of ZAP-70 through specific dephosphorylation at the inhibitory Tyr-292
      by the low molecular weight phosphotyrosine phosphatase (LMPTP).
AB  - The ZAP-70 protein-tyrosine kinase plays a central role in signaling from the T
      cell antigen receptor. Recruitment and activation of ZAP-70 are transient and are
      terminated by phosphorylation of negative regulatory tyrosine residues and
      dephosphorylation of positively acting sites. We report that the low molecular
      weight protein-tyrosine phosphatase (LMPTP) specifically dephosphorylates the
      negative regulatory Tyr-292 of ZAP-70, thereby counteracting inactivation of ZAP
      70. Expression of low levels of LMPTP resulted in increased ZAP-70
      phosphorylation, presumably at the activating Tyr-493 and other sites, increased
      kinase activity, and augmented downstream signaling to the mitogen-activated
      protein kinase pathway. The ZAP-70 Y292F mutant was not affected by LMPTP. Our
      results indicate that LMPTP, like CD45, dephosphorylates a negative regulatory
      tyrosine site in a protein-tyrosine kinase and thereby strengthens T cell
      receptor signaling.

PMID- 11976342
TI  - Loss of hyperpolarization-activated Cl(-) current in salivary acinar cells from
      Clcn2 knockout mice.
AB  - ClC-2 is localized to the apical membranes of secretory epithelia where it has
      been hypothesized to play a role in fluid secretion. Although ClC-2 is clearly
      the inwardly rectifying anion channel in several tissues, the molecular identity
      of the hyperpolarization-activated Cl(-) current in other organs, including the
      salivary gland, is currently unknown. To determine the nature of the
      hyperpolarization-activated Cl(-) current and to examine the role of ClC-2 in
      salivary gland function, a mouse line containing a targeted disruption of the
      Clcn2 gene was generated. The resulting homozygous Clcn2(-/-) mice lacked
      detectable hyperpolarization-activated chloride currents in parotid acinar cells
      and, as described previously, displayed postnatal degeneration of the retina and
      testis. The magnitude and biophysical characteristics of the volume- and calcium
      activated chloride currents in these cells were unaffected by the absence of ClC
      2. Although ClC-2 appears to contribute to fluid secretion in some cell types,
      both the initial and sustained salivary flow rates were normal in Clcn2(-/-) mice
      following in vivo stimulation with pilocarpine, a cholinergic agonist. In
      addition, the electrolytes and protein contents of the mature secretions were
      normal. Because ClC-2 has been postulated to contribute to cell volume control,
      we also examined regulatory volume decrease following cell swelling. However,
      parotid acinar cells from Clcn2(-/-) mice recovered volume with similar
      efficiency to wild-type littermates. These data demonstrate that ClC-2 is the
      hyperpolarization-activated Cl(-) channel in salivary acinar cells but is not
      essential for maximum chloride flux during stimulated secretion of saliva or
      acinar cell volume regulation.

PMID- 11976343
TI  - Insertion and topology of a plant viral movement protein in the endoplasmic
      reticulum membrane.
AB  - Virus-encoded movement proteins (MPs) mediate cell-to-cell spread of viral RNA
      through plant membranous intercellular connections, the plasmodesmata. The
      molecular pathway by which MPs interact with viral genomes and target
      plasmodesmata channels is largely unknown. The 9-kDa MP from carnation mottle
      carmovirus (CarMV) contains two potential transmembrane domains. To explore the
      possibility that this protein is in fact an intrinsic membrane protein, we have
      investigated its insertion into the endoplasmic reticulum membrane. By using in
      vitro translation in the presence of dog pancreas microsomes, we demonstrate that
      CarMV p9 inserts into the endoplasmic reticulum without the aid of any additional
      viral or plant host components. We further show that the membrane topology of
      CarMV p9 is N(cyt)-C(cyt) (N and C termini of the protein facing the cytoplasm)
      by in vitro translation of a series of truncated and full-length constructs with
      engineered glycosylation sites. Based on these results, we propose a topological
      model in which CarMV p9 is anchored in the membrane with its N- and C-terminal
      tail segments interacting with its soluble, RNA-bound partner CarMV p7, to
      accomplish the viral cell-to-cell movement function.

PMID- 11976344
TI  - Tumor necrosis factor-related apoptosis-inducing ligand-induced death-inducing
      signaling complex and its modulation by c-FLIP and PED/PEA-15 in glioma cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can trigger
      apoptosis in some tumor cells but not other tumor cells. To explore the signal
      transduction events in TRAIL-triggered apoptosis and its modulation in
      nontransfected tumor cells, we analyzed TRAIL-induced death-inducing signaling
      complex (DISC) in TRAIL-sensitive and -resistant glioma cells. Caspase-8 and
      caspase-10 were recruited to the DISC, where they were proteolytically activated
      to initiate apoptosis in TRAIL-sensitive glioma cells. Caspase-8 and caspase-10
      were also recruited to the DISC in TRAIL-resistant cells, but their further
      activation was inhibited by two antiapoptotic proteins termed cellular Fas
      associated death domain-like interleukin-1beta-converting enzyme-inhibitory
      protein (c-FLIP) and phosphoprotein enriched in diabetes/phosphoprotein enriched
      in astrocytes-15kDa (PED/PEA-15). Both long and short forms of c-FLIP were
      recruited to the DISC, where the long form c-FLIP was cleaved to produce
      intermediate fragments. Of the three isoforms of PED/PEA-15 proteins, only the
      doubly phosphorylated form was expressed and recruited to the DISC in TRAIL
      resistant cells, indicating that the phosphorylation status of PED/PEA-15
      determines its recruitment in the cells. Treatment with calcium/calmodulin
      dependent protein kinase inhibitor rescued TRAIL sensitivity in TRAIL-resistant
      cells, providing a potential new approach to sensitize the cells to TRAIL-induced
      apoptosis.

PMID- 11976345
TI  - The gene e.1 (nudE.1) of T4 bacteriophage designates a new member of the Nudix
      hydrolase superfamily active on flavin adenine dinucleotide, adenosine 5'
      triphospho-5'-adenosine, and ADP-ribose.
AB  - The T4 bacteriophage gene e.1 was cloned into an expression vector and expressed
      in Escherichia coli, and the purified protein was identified as a Nudix hydrolase
      active on FAD, adenosine 5'-triphospho-5'-adenosine (Ap(3)A), and ADP-ribose.
      Typical of members of the Nudix hydrolases, the enzyme has an alkaline pH optimum
      (pH 8) and requires a divalent cation for activity that can be satisfied by
      Mg(2+) or Mn(2+). For all substrates, AMP is one of the products, and unlike most
      of the other enzymes active on Ap(3)A, the T4 enzyme hydrolyzes higher homologues
      including Ap(4-6)A. This is the first member of the Nudix hydrolase gene
      superfamily identified in bacterial viruses and the only one present in T4.
      Although the protein was predicted to be orthologous to E. coli MutT on the basis
      of a sequence homology search, the properties of the gene and of the purified
      protein do not support this notion because of the following. (a) The purified
      enzyme hydrolyzes substrates not acted upon by MutT, and it does not hydrolyze
      canonical MutT substrates. (b) The e.1 gene does not complement mutT1 in vivo.
      (c) The deletion of e.1 does not increase the spontaneous mutation frequency of
      T4 phage. The properties of the enzyme most closely resemble those of Orf186 of
      E. coli, the product of the nudE gene, and we therefore propose the mnemonic
      nudE.1 for the T4 phage orthologue.

PMID- 11976346
TI  - Reconstitution of mRNA editing in yeast using a Gal4-apoB-Gal80 fusion transcript
      as the selectable marker.
AB  - We describe a fusion transcript of Gal4 linked to its specific inhibitor protein
      Gal80 by 276 nucleotides of apolipoprotein (apo) B sequence as a selectable
      marker for mRNA editing. Editing of apoB mRNA is catalyzed by an editing enzyme
      complex that introduces a stop codon by deamination of C to U. The catalytic
      subunit APOBEC-1 is a cytidine deaminase and requires a second essential
      component recently cloned and termed APOBEC-1 complementing factor (ACF) or
      APOBEC-1-stimulating protein (ASP). The aim of this study was to demonstrate that
      APOBEC-1 plus ACF/ASP comprise all that is required for editing of apoB mRNA in
      vivo. Expression of APOBEC-1 and Gal4 fused to its inhibitor Gal80 by an
      intervening unedited apoB sequence (Gal4-apoB(C)-Gal80) did not result in the
      Gal4-dependent expression of HIS3 and beta-galactosidase in the yeast strain
      CG1945. Co-expression of APOBEC-1 and ACF/ASP induced editing of the apoB site in
      up to 13% of the Gal4-apoB(C)-Gal80 transcripts and enabled selection of yeast
      cells for robust expression of HIS3 and beta-galactosidase. Additional expression
      of the alternative splicing regulatory protein KSRP increased the editing of the
      apoB site by APOBEC-1 and ACF/ASP to 21%. Thus, APOBEC-1 and ACF/ASP represent
      the core apoB mRNA editing enzyme in vivo. This study demonstrates for the first
      time the successful use of a selectable marker for mRNA editing. The Gal4-Gal80
      system is analogous to the two-hybrid assay and may have broader applications for
      the study of other mRNA processing reactions.

PMID- 11976347
TI  - Shear stress-induced release of basic fibroblast growth factor from endothelial
      cells is mediated by matrix interaction via integrin alpha(v)beta3.
AB  - Considering that chronic elevation of shear stress results in remodeling of the
      vasculature, we analyzed whether mechanical load could mediate basic fibroblast
      growth factor (bFGF) release and whether bFGF would act as mediator of shear
      stress-induced endothelial proliferation and differentiation. Supernatant media
      of shear stress-exposed endothelial cells (EC) contained significantly higher
      amounts of bFGF than medium from static cells. Released bFGF was fully intact
      with regard to its function as an inductor of proliferation and differentiation.
      Shear stress-conditioned media induced capillary-like structure formation,
      whereas static control medium did not. Likewise, only shear stress-conditioned
      medium induced proliferation of serum starved EC. Both capillary-like structure
      formation and proliferation could be inhibited by neutralization of bFGF or its
      receptor. The release of bFGF was subject to specific, integrin-mediated control,
      since inhibition of alpha(v)beta(3) integrin prevented it, whereas inhibition of
      alpha(5)beta(1) integrin had no effect. We conclude that shear stress induces the
      release of bFGF from EC in a tightly controlled manner. The release is dependent
      on specific cell-matrix interactions via alpha(v)beta(3) integrins. The effects
      on cell proliferation and differentiation suggest that release of bFGF is
      functionally significant and may represent a necessary initial step in adaptive
      remodeling processes induced by shear stress.

PMID- 11976348
TI  - The mechanics of wave-swept algae.
AB  - Wave-swept marine algae must contend with the hydrodynamic forces imposed by
      extreme water velocities. Nonetheless, they seldom have a shape that appears
      streamlined and they are constructed of weak, compliant materials. How do they
      survive? The answer is complex, but a coherent story is beginning to emerge. The
      combined effect of frond shape and material properties ensures that algae are
      flexible. In small individuals, flexibility allows the plant to reorient and
      reconfigure in flow, thereby assuming a streamlined shape and reducing the
      applied hydrodynamic force. In large individuals, flexibility allows fronds to
      'go with the flow', a strategy that can at times allow the plant to avoid
      hydrodynamic forces but may at other times impose inertial loads. Our
      understanding of algal mechanics is such that we can begin to predict the
      survivorship of algae as a function of size, spatial distribution and wave
      climate.

PMID- 11976349
TI  - Glomerular representation of plant volatiles and sex pheromone components in the
      antennal lobe of the female Spodoptera littoralis.
AB  - We studied the projection patterns of antennal lobe (AL) interneurones sensitive
      to plant volatiles and female-produced sex pheromone components in the female
      moth, Spodoptera littoralis. Ten compounds (eight plant-derived compounds and two
      sex pheromone components) were singly applied to the antenna and, using
      intracellular recording and staining techniques, the physiological and
      morphological characteristics of responding neurones were investigated. In
      addition, ALs stained with a synapsin antibody were optically sectioned using
      confocal microscopy, and a three-dimensional map of glomeruli in the anterior
      aspect of the AL was reconstructed. We used the map as a reference for
      identification of glomeruli innervated by projection neurones (PNs) that respond
      to plant volatiles and/or pheromone components. Nineteen PNs, responding to one
      to seven compounds of the ten tested stimuli, were stained with neurobiotin.
      These neurones each arborised in a single glomerulus in the frontal side of the
      AL. PNs responding to the same compound arborised in different glomeruli and PNs
      arborising in the same glomerulus responded to different compounds. Accordingly,
      glomeruli harbouring the dendritic arborisations of PNs responding to each of the
      tested compounds constituted a unique array of glomeruli that were not
      necessarily adjacent. It was thus clear that, at the output level, a single plant
      volatile or a sex pheromone component was not represented within a single
      glomerulus in the AL. We expect complex patterns of glomeruli to be involved in
      the coding of plant-derived compounds, as well as sex pheromone components, in
      female S. littoralis.

PMID- 11976350
TI  - Structural flexibility of the small intestine and liver of garter snakes in
      response to feeding and fasting.
AB  - Garter snakes Thamnophis sirtalis parietalis feed frequently but also tolerate
      extended periods of fasting when food is unavailable. We studied the dynamics,
      reversibility and repeatability of size changes of the small intestine and liver
      using ultrasonography. We employed light and transmission electron microscopy and
      flow cytometry to study the tissue mechanism that drives this flexibility. We
      compared garter snakes that fed every other day, snakes that fed once a week and
      fasting snakes. In all feeding trials, the size of the small intestine and the
      liver increased rapidly after feeding. Constantly feeding snakes maintained an
      elevated level of organ size, while snakes that were fed only once a week showed
      a marked up- and downregulation of organ size. Histology revealed the mucosal
      epithelium to be a transitional epithelium that can change cell configuration
      considerably to accommodate organ size changes. Upregulation of small intestine
      and liver size was always associated with the incorporation of lipid droplets
      into enterocytes and hepatocytes. Cell proliferation was not involved in
      upregulation of organ size. In contrast, cell proliferation increased during
      downregulation of organ size, indicating that cells worn out during digestion
      were replaced. The dynamics of flexibility and the functional features of the
      tissue were the same as described for the Burmese python Python molurus
      bivittatus. We suggest that garter snakes employ the same energetically cheap
      mechanism of organ size regulation as pythons, which allows for rapid, repeated
      and reversible size changes with no cell proliferation involved. Comparative
      evidence suggests that the transitional mucosal epithelium is an ancestral
      character of snakes and that feeding ecology is not directly related to the
      cytological features of the mucosal epithelium.

PMID- 11976351
TI  - Estimates of circulation and gait change based on a three-dimensional kinematic
      analysis of flight in cockatiels (Nymphicus hollandicus) and ringed turtle-doves
      (Streptopelia risoria).
AB  - Birds and bats are known to employ two different gaits in flapping flight, a
      vortex-ring gait in slow flight and a continuous-vortex gait in fast flight. We
      studied the use of these gaits over a wide range of speeds (1-17 ms(-1)) and
      transitions between gaits in cockatiels (Nymphicus hollandicus) and ringed turtle
      doves (Streptopelia risoria) trained to fly in a recently built, variable-speed
      wind tunnel. Gait use was investigated via a combination of three-dimensional
      kinematics and quasi-steady aerodynamic modeling of bound circulation on the
      distal and proximal portions of the wing. Estimates of lift from our circulation
      model were sufficient to support body weight at all but the slowest speeds (1 and
      3 ms(-1)). From comparisons of aerodynamic impulse derived from our circulation
      analysis with the impulse estimated from whole-body acceleration, it appeared
      that our quasi-steady aerodynamic analysis was most accurate at intermediate
      speeds (5-11 ms(-1)). Despite differences in wing shape and wing loading, both
      species shifted from a vortex-ring to a continuous-vortex gait at 7 ms(-1). We
      found that the shift from a vortex-ring to a continuous-vortex gait (i) was
      associated with a phase delay in the peak angle of attack of the proximal wing
      section from downstroke into upstroke and (ii) depended on sufficient forward
      velocity to provide airflow over the wing during the upstroke similar to that
      during the downstroke. Our kinematic estimates indicated significant variation in
      the magnitude of circulation over the course the wingbeat cycle when either
      species used a continuous-vortex gait. This variation was great enough to suggest
      that both species shifted to a ladder-wake gait as they approached the maximum
      flight speed (cockatiels 15 ms(-1), doves 17 ms(-1)) that they would sustain in
      the wind tunnel. This shift in flight gait appeared to reflect the need to
      minimize drag and produce forward thrust in order to fly at high speed. The
      ladder-wake gait was also employed in forward and vertical acceleration at medium
      and fast flight speeds.

PMID- 11976352
TI  - Mitochondrial ATP-sensitive K+ channels influence force development and anoxic
      contractility in a flatfish, yellowtail flounder Limanda ferruginea, but not
      Atlantic cod Gadus morhua heart.
AB  - The influence of ATP-sensitive K+ channels (K(ATP) channels) on cardiac
      performance during anoxia and reoxygenation was investigated in two species of
      fish showing different cardiac responses to anoxia. Force production in
      isometrically contracting ventricular muscle preparations from yellowtail
      flounder is potentiated at the onset of anoxia, while force immediately declines
      in Atlantic cod preparations. Glibenclamide, a general K(ATP) blocker, impaired
      oxygenated force development in yellowtail flounder heart but was without effect
      on cod preparations. The mitochondrial K(ATP) (mK(ATP))-specific blocker 5
      hydroxydecanoic acid (5HD) improved oxygenated force production in yellowtail
      flounder heart without influencing contractility during anoxia or reoxygenation.
      The specific mK(ATP) agonist diazoxide preserved resting tension and eliminated
      anoxic force potentiation in yellowtail flounder heart preparations. Neither 5HD
      nor diazoxide affected contractility in cod ventricle preparations. Results
      indicate that K(ATP) channels can modulate contractility in yellowtail flounder
      heart and are potentially important in cardiac hypoxia survival in this species.

PMID- 11976353
TI  - The freeze-avoidance response of smelt Osmerus mordax: initiation and subsequent
      suppression of glycerol, trimethylamine oxide and urea accumulation.
AB  - Smelt (Osmerus mordax) were maintained at either ambient water temperature or
      approximately 5 degrees C and various aspects of their freeze-avoidance response
      were examined from early winter until early spring. Plasma levels of glycerol,
      trimethylamine oxide (TMAO) and urea were elevated by December 15 and continued
      to increase in fish held in ambient conditions. In contrast, fish held under warm
      conditions exhibited decreased glycerol and urea content in plasma, muscle and
      liver. Plasma and liver TMAO levels also decreased in these fish while muscle
      TMAO did not vary from the initial values. The activity of liver enzymes involved
      with the production of glycerol did not differ significantly between groups and
      had decreased by the end of the study. Antifreeze protein (AFP) expression
      increased over the duration of the experiment. In January samples, AFP activity
      (thermal hysteresis) did not vary significantly between groups but mRNA levels
      were significantly lower in the smelt held at warm temperatures.

PMID- 11976354
TI  - Temporal determinants of long-term retention of olfactory memory in the cricket
      Gryllus bimaculatus.
AB  - Temporal determinants of olfactory long-term memory retention in the cricket
      Gryllus bimaculatus were studied. Elementary appetitive and aversive conditioning
      procedures, as well as a differential conditioning procedure, were applied. In
      appetitive conditioning, peppermint odour was paired with a water reward. In
      aversive conditioning, vanilla odour was paired with saline solution. In
      differential conditioning, an appetitive conditioning trial was followed by an
      aversive conditioning trial. The odour preference of crickets was tested before
      and 2 h, 1 day and 4 days after training by allowing the crickets to choose
      between peppermint or vanilla sources. Differential conditioning or appetitive
      conditioning alone led to long-lasting memory retention with no significant decay
      from 2 h to 4 days after training, but retention after aversive conditioning was
      absent 1 day after training. Studies using differential conditioning have shown
      (i) that four trials are sufficient to cause a saturated level of acquisition,
      (ii) that conditioning is successful when the conditioned stimulus is presented
      immediately or 5 s before the onset of presentation of the unconditioned
      stimulus, (iii) that the optimal interval between trials is 2-5 min, and (iv)
      that anaesthetic treatment with CO2 given immediately after training results in
      memory disruption but that anaesthetic-resistant memory develops fully 20 min
      after training. This study demonstrates that a differential conditioning
      procedure is particularly effective for the formation of long-term memory.

PMID- 11976355
TI  - Fertilization in the sea: the chemical identity of an abalone sperm attractant.
AB  - Chemical communication between sperm and egg is a key factor mediating sexual
      reproduction. Dissolved signal molecules that cause sperm to orient and
      accelerate towards an egg could play pivotal roles in fertilization success, but
      such compounds are largely undescribed. This investigation considered the
      behavioral responses of red abalone (Haliotis rufescens) sperm to soluble factors
      released into sea water by conspecific eggs. Sperm in proximity to individual
      live eggs swam significantly faster and oriented towards the egg surface.
      Bioassay-guided fractionation was employed to isolate the chemoattractant,
      yielding a single pure, fully active compound after reversed-phase and size
      exclusion high-performance liquid chromatography. Chemical characterization by
      nuclear magnetic resonance spectroscopy indicated that the free amino acid L
      tryptophan was the natural sperm attractant in H. rufescens. Eggs released L
      tryptophan at concentrations that triggered both activation and chemotaxis in
      sperm, exhibiting significant activity at levels as low as 10(-8) mol x l(-1).
      The D-isomer of tryptophan was inactive, showing that the sperm response was
      stereospecific. Serotonin, a potent neuromodulator and tryptophan metabolite, had
      no effect on sperm swim speeds or on orientation. In experimental treatments
      involving an elevated, uniform concentration of tryptophan (10(-7) mol x l(-1))
      or the addition of tryptophanase, an enzyme that selectively digests tryptophan,
      sperm failed to navigate towards live eggs. A natural gradient of L-tryptophan
      was therefore necessary and sufficient to promote recruitment of sperm to the
      surface of eggs in red abalone.

PMID- 11976356
TI  - The use of viewing posture to control visual processing by lateralised
      mechanisms.
AB  - Chicks were trained and tested to run to a dish and feed from it under one of
      four conditions. In three of these, the dish was covered by a light lid that the
      chicks readily learned to remove. The square lid (SL) had slightly protruding
      corners, so that it could be removed by a blow of the bill at a range of
      positions. A round lid (UL), which fitted snugly, could best be removed by
      inserting the bill into a medial U-shaped indentation. A round lid (STR), which
      fitted all the way round to the edge of the dish, could be removed by grasping
      and tugging a centrally placed piece of string. The final dish had no lid (NOL).
      The dish and the layout of the arena were otherwise identical under all
      conditions. Chicks trained and tested with lids predominantly fixated the dish
      during approach with the right eye and showed leftward deviation from the direct
      line of approach (which facilitated right eye use). NOL chicks fixated with the
      left eye and deviated rightwards. The right eye is thus used when a motor plan
      has to be set up and sustained. The use of the left eye is expected when
      topographical information has to be used. Here, the approach was so simple and
      practised that the assumption of left eye viewing is likely to be a default
      condition. It would facilitate detection of any change in layout. A standard set
      of head positions were used, particularly by SL and NOL chicks, showing that the
      head was aligned with some reference point, perhaps the centre of the dish. These
      fell into two series (used by both eyes), and in both the peaks of frequent use
      were 10 degrees apart. One (20 degrees, 10 degrees ) was probably generated by
      head saccades ending with the bill pointing directly at the dish (0 degrees ).
      The other (35 degrees, 25 degrees, 15 degrees ) is best explained by slight
      divergence of the optic axes. The 25 degrees right eye position was consistently
      used by STR chicks at the beginning of approach. The STR condition requires the
      most difficult manipulation, and the manipulandum is most obvious from a
      distance. This is consistent with right eye use during establishment of a motor
      plan. Head postures consistent with divergence were also used when close to the
      dish under conditions where choice between targets was necessary. This was clear
      in the NOL condition, where the chick could see the food grains as it approached.
      Here, it is likely that both eyes are used in independent search. If so, it may
      be that divergence is used as a strategy during establishment of a motor plan (as
      in STR chicks) to increase the independence of the right eye system.

PMID- 11976357
TI  - Evidence for a role of GABA and Mas-allatotropin in photic entrainment of the
      circadian clock of the cockroach Leucophaea maderae.
AB  - Accumulating evidence suggests that the accessory medulla is the location of the
      circadian pacemaker in the fruit fly Drosophila melanogaster and the cockroach
      Leucophaea maderae. gamma-Aminobutyric acid (GABA) and Mas-allatotropin are two
      putative neurotransmitters, in the accessory medulla in the cockroach Leucophaea
      maderae. Neurons immunoreactive to the neuropeptide Mas-allatotropin are local
      neurons with arborizations in the noduli of the accessory medulla, while GABA
      immunoreactive neurons connect the noduli of the accessory medulla to the medulla
      and to the lamina via processes in the distal tract. Injections of GABA and Mas
      allatotropin into the vicinity of the accessory medulla resulted in stable phase
      dependent resetting of the circadian locomotor activity of the cockroach. The
      resulting phase response curves closely matched light-dependent phase response
      curves, suggesting that both substances play a role in circuits relaying photic
      information from circadian photoreceptors to the central pacemaker.

PMID- 11976358
TI  - Brainstem lateral line responses to sinusoidal wave stimuli in still and running
      water.
AB  - The fish lateral line consists of superficial and canal neuromasts. In still
      water, afferent fibers from both types of neuromast respond equally well to a
      sinusoidally vibrating sphere. In running water, responses to a vibrating sphere
      of fibers innervating superficial neuromasts are masked. In contrast, responses
      of fibers innervating canal neuromasts are barely altered. It is not known
      whether this functional subdivision of the peripheral lateral line is maintained
      in the brain. We studied the effect of running water on the responses to a 50 Hz
      vibrating sphere of single units in the medial octavolateralis nucleus (MON) in
      goldfish Carassius auratus. The MON is the first site of central processing of
      lateral line information. Three types of units were distinguished. Type I units
      (N=27) were flow-sensitive; their ongoing discharge rates either increased or
      decreased in running water, and as a consequence, responses of these units to the
      vibrating sphere were masked in running water. Type II units (N=7) were not flow
      sensitive; their ongoing discharge rates were comparable in still and running
      water, so their responses to the vibrating sphere were not masked in running
      water. Type III units (N=7) were also not flow-sensitive, but their responses to
      the vibrating sphere were nevertheless masked in running water. Although
      interactions between the superficial and canal neuromast system cannot be ruled
      out, our data indicate that the functional subdivision of the lateral line
      periphery is maintained to a large degree at the level of the medial
      octavolateralis nucleus.

PMID- 11976359
TI  - Mechanical power output during running accelerations in wild turkeys.
AB  - We tested the hypothesis that the hindlimb muscles of wild turkeys (Meleagris
      gallopavo) can produce maximal power during running accelerations. The mechanical
      power developed during single running steps was calculated from force-plate and
      high-speed video measurements as turkeys accelerated over a trackway. Steady
      speed running steps and accelerations were compared to determine how turkeys
      alter their running mechanics from a low-power to a high-power gait. During
      maximal accelerations, turkeys eliminated two features of running mechanics that
      are characteristic of steady-speed running: (i) they produced purely propulsive
      horizontal ground reaction forces, with no braking forces, and (ii) they produced
      purely positive work during stance, with no decrease in the mechanical energy of
      the body during the step. The braking and propulsive forces ordinarily developed
      during steady-speed running are important for balance because they align the
      ground reaction force vector with the center of mass. Increases in acceleration
      in turkeys correlated with decreases in the angle of limb protraction at toe-down
      and increases in the angle of limb retraction at toe-off. These kinematic changes
      allow turkeys to maintain the alignment of the center of mass and ground reaction
      force vector during accelerations when large propulsive forces result in a
      forward-directed ground reaction force. During the highest accelerations, turkeys
      produced exclusively positive mechanical power. The measured power output during
      acceleration divided by the total hindlimb muscle mass yielded estimates of peak
      instantaneous power output in excess of 400 W kg(-1) hindlimb muscle mass. This
      value exceeds estimates of peak instantaneous power output of turkey muscle
      fibers. The mean power developed during the entire stance phase increased from
      approximately zero during steady-speed runs to more than 150 W kg(-1) muscle
      during the highest accelerations. The high power outputs observed during
      accelerations suggest that elastic energy storage and recovery may redistribute
      muscle power during acceleration. Elastic mechanisms may expand the functional
      range of muscle contractile elements in running animals by allowing muscles to
      vary their mechanical function from force-producing struts during steady-speed
      running to power-producing motors during acceleration.

PMID- 11976360
TI  - Feeding patterns of Chelus fimbriatus (Pleurodira: Chelidae).
AB  - The kinematics of feeding on fish have been studied in the aquatic feeding
      specialist Chelus fimbriatus, the fringed turtle, to provide a basic description
      of complete feeding cycles. Anatomical findings supplement the kinematic results.
      High-speed video (500 frames x s(-1)) recordings and X-ray film (150 frames x s(
      1)) are used to analyse the kinematic variables characterizing head, hyoid,
      oesophageal and prey movements. The high velocities, especially of mouth opening,
      the forward thrust of the head and suction of the prey, are unique among turtles
      and comparable with those of aquatic salamanders and certain fishes
      (unidirectional feeders, in contrast to Chelus fimbriatus). The expandability of
      the pharynx and the anterior half of the oesophagus enables a specific type of
      unidirectional flow, at least during the early stages of the feeding cycle. This
      considerably improves the feeding performance compared with that of other aquatic
      turtles. The streamlined shape of the skull, the large hyoid apparatus, the
      highly reduced tongue and the extremely distensible oesophagus support the
      kinematics to a great extent, making C. fimbriatus a specialized suction feeder
      that can be regarded as one endpoint in the feeding evolution of aquatic
      reptiles.

PMID- 11976361
TI  - A three-dimensional computational study of the aerodynamic mechanisms of insect
      flight.
AB  - A finite element flow solver was employed to compute unsteady flow past a three
      dimensional Drosophila wing undergoing flapping motion. The computed thrust and
      drag forces agreed well with results from a previous experimental study. A grid
      refinement study was performed to validate the computational results, and a grid
      independent solution was achieved. The effect of phasing between the
      translational and rotational motions was studied by varying the rotational motion
      prior to the stroke reversal. It was observed that, when the wing rotation is
      advanced with respect to the stroke reversal, the peak in the thrust forces is
      higher than when the wing rotation is in phase with the stroke reversal and that
      the peak thrust is reduced further when the wing rotation is delayed. As
      suggested by previous authors, we observe that the rotational mechanism is
      important and that the combined translational and rotational mechanisms are
      necessary to describe accurately the force time histories and unsteady
      aerodynamics of flapping wings.

PMID- 11976362
TI  - Intracellular pH response to anoxia in acutely dissociated adult rat hippocampal
      CA1 neurons.
AB  - The effects of anoxia on intracellular pH (pH(i)) were examined in acutely
      isolated adult rat hippocampal CA1 neurons loaded with the H(+)-sensitive
      fluorophore, 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. During
      perfusion with HCO/CO(2)- or HEPES-buffered media (pH 7.35) at 37 degrees C, 5-
      or 10-min anoxic insults were typified by an intracellular acidification on the
      induction of anoxia, a subsequent rise in pH(i) in the continued absence of O(2),
      and a further internal alkalinization on the return to normoxia. The steady-state
      pH(i) changes were not consequent on changes in [Ca(2+)](i) and, examined in the
      presence of HCO, were not significantly affected by (DIDS). In the absence of
      HCO, the magnitude of the postanoxic alkalinization was attenuated when external
      Na(+) was reduced by substitution with N-methyl-D-glucamine (NMDG(+)), but not
      Li(+), suggesting that increased Na(+)/H(+) exchange activity contributes to this
      phase of the pH(i) response. In contrast, 100-500 microM Zn(2+), a known blocker
      of H(+)-conductive pathways, reduced the magnitudes of the internal
      alkalinizations that occurred both during and following anoxia. The effects of
      NMDG(+)-substituted medium and Zn(2+) to reduce the increase in pH(i) that
      occurred after anoxia were additive. Consistent with the steady-state pH(i)
      changes, rates of pH(i) recovery from internal acid loads imposed immediately
      after anoxia were increased, and the application of Zn(2+) and/or perfusion with
      NMDG(+)-substituted medium slowed pH(i) recovery. Reducing extracellular pH from
      7.35 to 6.60, or reducing ambient temperature from 37 degrees C to room
      temperature, also attenuated the increases in steady-state pH(i) observed during
      and after anoxia and reduced rates of pH(i) recovery from acid loads imposed in
      the immediate postanoxic period. Finally, inhibition of the cAMP/protein kinase A
      second-messenger system reduced the magnitude of the rise in pH(i) after anoxia
      in a manner that was dependent on external Na(+); conversely, activation of the
      system with isoproterenol increased the postanoxic alkalinization, an effect that
      was attenuated by pretreatment with propranolol, Rp-cAMPS, or when NMDG(+) (but
      not Li(+)) was employed as an external Na(+) substitute. The results suggest that
      a Zn(2+)-sensitive acid efflux mechanism, possibly a H(+)-conductive pathway
      activated by membrane depolarization, contributes to the internal alkalinization
      observed during anoxia in adult rat CA1 neurons. The rise in pH(i) after anoxia
      reflects acid extrusion via the H(+)-conductive pathway and also Na(+)/H(+)
      exchange, activation of the latter being mediated, at least in part, through a
      cAMP-dependent signaling pathway.

PMID- 11976363
TI  - Biphasic modulation of spinal visceral nociceptive transmission from the
      rostroventral medial medulla in the rat.
AB  - Descending inhibitory and facilitatory influences from the rostroventral medulla
      (RVM) on responses of lumbosacral spinal neurons to noxious colorectal distension
      (CRD, 80 mmHg, 20 s) were studied. At 25 sites in the RVM, electrical stimulation
      produced biphasic effects, facilitating responses of spinal neurons to CRD at
      lesser intensities of stimulation (5-25 microA) and inhibiting responses of the
      same neurons at greater intensities of stimulation (50-100 microA). At 38 other
      sites in the RVM, electrical stimulation produced only intensity-dependent
      inhibition of neuron responses to CRD. At another 13 sites in the RVM, electrical
      stimulation (5-100 microA) produced only facilitatory effects on responses to
      CRD. Descending modulatory effects were selective for distension-evoked activity;
      spontaneous activities of the same spinal neurons were not significantly affected
      by electrical stimulation that either facilitated or inhibited neuron responses
      to CRD. Neuron responses to graded CRD (20-100 mmHg) were positively accelerating
      functions that were shifted leftward or rightward, respectively, by lesser,
      facilitatory intensities or greater, inhibitory intensities of RVM stimulation. L
      glutamate microinjection into the RVM replicated the effects of electrical
      stimulation, producing similar biphasic modulatory effects as produced by
      electrical stimulation. Microinjection of glutamate into the RVM at a low dose (5
      nmoles) facilitated responses of spinal neurons to CRD and inhibited responses of
      the same neurons at a greater dose (50 nmoles). In some experiments,
      microinjection of lidocaine (0.5 microl of 4% solution) or the neurotoxin
      ibotenic acid (0.5 microl, 10 microg) into the RVM produced reversible or long
      lasting, respectively, decreases in spontaneous activity and responses of spinal
      neurons to CRD. These results reveal that spinal visceral nociceptive
      transmission is subject to a tonic descending excitatory influence from the RVM
      and that descending modulatory effects from the RVM on visceral nociceptive
      transmission are qualitatively similar to modulation of cutaneous nociceptive
      transmission.

PMID- 11976364
TI  - Neural representations of sinusoidal amplitude and frequency modulations in the
      primary auditory cortex of awake primates.
AB  - We investigated neural coding of sinusoidally modulated tones (sAM and sFM) in
      the primary auditory cortex (A1) of awake marmoset monkeys, demonstrating that
      there are systematic cortical representations of embedded temporal features that
      are based on both average discharge rate and stimulus-synchronized discharge
      patterns. The rate-representation appears to be coded alongside the stimulus
      synchronized discharges, such that the auditory cortex has access to both rate
      and temporal representations of the stimulus at high and low frequencies,
      respectively. Furthermore, we showed that individual auditory cortical neurons,
      as well as populations of neurons, have common features in their responses to
      both sAM and sFM stimuli. These results may explain the similarities in the
      perception of sAM and sFM stimuli as well as the different perceptual qualities
      effected by different modulation frequencies. The main findings include the
      following. 1) Responses of cortical neurons to sAM and sFM stimuli in awake
      marmosets were generally much stronger than responses to unmodulated tones. Some
      neurons responded to sAM or sFM stimuli but not to pure tones. 2) The discharge
      rate-based modulation transfer function typically had a band-pass shape and was
      centered at a preferred modulation frequency (rBMF). Population-averaged mean
      firing rate peaked at 16- to 32-Hz modulation frequency, indicating that the A1
      was maximally excited by this frequency range of temporal modulations. 3) Only
      approximately 60% of recorded units showed statistically significant discharge
      synchrony to the modulation waveform of sAM or sFM stimuli. The discharge
      synchrony-based best modulation frequency (tBMF) was typically lower than the
      rBMF measured from the same neuron. The distribution of rBMF over the population
      of neurons was approximately one octave higher than the distribution of tBMF. 4)
      There was a high degree of similarity between cortical responses to sAM and sFM
      stimuli that was reflected in both discharge rate- or synchrony-based response
      measures. 5) Inhibition appeared to be a contributing factor in limiting
      responses at modulation frequencies above the rBMF of a neuron. And 6) neurons
      with shorter response latencies tended to have higher tBMF and maximum discharge
      synchrony frequency than those with longer response latencies. rBMF was not
      significantly correlated with the minimum response latency.

PMID- 11976365
TI  - Octopus cells of the mammalian ventral cochlear nucleus sense the rate of
      depolarization.
AB  - Whole cell patch recordings in slices show that the probability of firing of
      action potentials in octopus cells of the ventral cochlear nucleus depends on the
      dynamic properties of depolarization. Octopus cells fired only when the rate of
      rise of a depolarization exceeded a threshold value that varied between 5 and 15
      mV/ms among cells. The threshold rate of rise was independent of whether
      depolarizations were evoked synaptically or by the intracellular injection of
      current. Previous work showed that octopus cells are contacted by many auditory
      nerve fibers, each providing less than 1-mV depolarization. Summation of synaptic
      input from multiple fibers is required for an octopus cell to reach threshold. In
      firing only when synaptic depolarization exceeds a threshold rate, octopus cells
      fire selectively when synaptic input is sufficiently large and synchronized for
      the small, brief unitary excitatory postsynaptic potentials (EPSPs) to sum to
      produce a rapidly rising depolarization. The sensitivity to rate of
      depolarization is governed by a low-threshold, alpha-dendrotoxin-sensitive
      potassium conductance (g(KL)). This conductance also shapes the peaks of action
      potentials, contributing to the precision in their timing. Firing in neighboring
      T stellate cells depends much less strongly on the rate of rise. They lack strong
      alpha-dendrotoxin-sensitive conductances. Octopus cells appear to be specialized
      to detect synchronization in the activation of groups of auditory nerve fibers, a
      common pattern in responses to natural sounds, and convey its occurrence with
      temporal precision.

PMID- 11976366
TI  - Stimulation pattern that maximizes force in paralyzed and control whole thenar
      muscles.
AB  - The pattern of seven pulses that elicited maximal thenar force was determined for
      control muscles and those that have been paralyzed chronically by spinal cord
      injury. For each subject group (n = 6), the peak force evoked by two pulses
      occurred at a short interval (5-15 ms; a "doublet"), but higher mean relative
      forces were achieved in paralyzed versus control muscles (41.4 +/- 3.9% vs. 22.7
      +/- 2.0% maximal). Thereafter, longer intervals evoked peak force in each type of
      muscle (mean: 35 +/- 1 ms, 36 +/- 2 ms, respectively). With seven pulses,
      paralyzed and control muscles reached 76.4 +/- 5.6% and 57.0 +/- 2.6% maximal
      force, respectively. These force differences resulted from significantly greater
      doublet/twitch and doublet/tetanic force ratios in paralyzed (2.73 +/- 0.08, 0.35
      +/- 0.03) compared with control muscles (2.07 +/- 0.07, 0.25 +/- 0.01). The
      greater force enhancement produced in paralyzed muscles with two closely spaced
      pulses may relate to changes in muscle stiffness and calcium metabolism. Peak
      force-time integrals were also achieved with an initial short interpulse
      interval, followed by longer intervals. The postdoublet intervals that produced
      peak force-time integrals in paralyzed and control muscles were longer than those
      for peak force, however (77 +/- 3 ms, 95 +/- 4 ms, respectively). These data show
      that the pulse patterns that maximize force and force-time integral in paralyzed
      muscles are similar to those that maximize these parameters in single motor units
      and various whole muscles across species. Thus the changes in neuromuscular
      properties that occur with chronic paralysis do not strongly influence the pulse
      pattern that optimizes muscle force or force-time integral.

PMID- 11976367
TI  - Eye-hand coordination: saccades are faster when accompanied by a coordinated arm
      movement.
AB  - When primates reach for an object, they very often direct an eye movement toward
      the object as well. This pattern of directing both eye and limb movements to the
      same object appears to be fundamental to eye-hand coordination. We investigated
      interactions between saccades and reaching movements in a rhesus monkey model
      system. The amplitude and peak velocity of isolated eye movements are positively
      correlated with one another. This relationship is called the main sequence. We
      now report that the main sequence relationship for saccades is changed during
      coordinated eye and arm movements. In particular, peak eye velocity is
      approximately 4% faster for the same size saccade when the saccade is accompanied
      by a coordinated arm movement. Saccade duration is reduced by an equivalent
      amount. The main sequence relationship is unperturbed when the arm moves
      simultaneously but in the opposite direction as the eyes, suggesting that eye and
      arm movements must be tightly coordinated to produce the effect. Candidate areas
      mediating this interaction include the posterior parietal cortex and the superior
      colliculus.

PMID- 11976368
TI  - Noradrenaline excites and inhibits GABAergic transmission in parvocellular
      neurons of rat hypothalamic paraventricular nucleus.
AB  - Noradrenaline (NA) is a major neurotransmitter that regulates many neuroendocrine
      and sympathetic autonomic functions of the hypothalamic paraventricular nucleus
      (PVN). Previously NA has been shown to increase the frequency of excitatory
      synaptic activity of parvocellular neurons within the PVN, but little is known
      about its effects on inhibitory synaptic activity. In this work, we studied the
      effects of NA (1-100 microM) on the spontaneous inhibitory synaptic currents
      (sIPSC) of type II PVN neurons in brain slices of the rat using the whole cell
      patch-clamp technique. Spontaneous IPSCs were observed from most type II neurons
      (n = 121) identified by their anatomical location within the PVN and their
      electrophysiological properties. Bath application of NA (100 microM) increased
      sIPSC frequency by 256% in 59% of the neurons. This effect was blocked by
      prazosin (2-20 microM), the alpha(1)-adrenoceptor antagonist and mimicked by
      phenylephrine (10-100 microM), the alpha(1)-adrenoceptor agonist. However, in 33%
      of the neurons, NA decreased sIPSC frequency by 54%, and this effect was blocked
      by yohimbine (2-20 microM), the alpha(2)-adrenoceptor antagonist and mimicked by
      clonidine (50 microM), the alpha(2)-adrenoceptor agonist. The Na(+) channel
      blocker, tetrodotoxin (0.1 microM) blocked the alpha(1)-adrenoceptor-mediated
      effect, but not the alpha(2)-adreonoceptor-mediated one. Both of the stimulatory
      and inhibitory effects of NA on sIPSC frequency were observed in individual
      neurons when tested with NA alone, or both phenylephrine and clonidine.
      Furthermore, in most neurons that showed the stimulatory effects, the inhibitory
      effects of NA were unmasked after blocking the stimulatory effects by prazosin or
      tetrodotoxin. These data indicate that tonic GABAergic inputs to the majority of
      type II PVN neurons are under a dual noradrenergic modulation, the increase in
      sIPSC frequency via somatic or dendritic alpha(1)-adrenoceptors and the decrease
      in sIPSC frequency via axonal terminal alpha(2)-adrenoceptors on the presynaptic
      GABAergic neurons.

PMID- 11976369
TI  - Noradrenaline increases high-frequency firing at the calyx of Held synapse during
      development by inhibiting glutamate release.
AB  - The mammalian auditory brain stem receives profuse adrenergic innervation, whose
      function is poorly understood. Here we investigate, during postnatal development,
      the effect of noradrenaline (NA) at the calyx of Held synapse in the rat medial
      nucleus of the trapezoid body (MNTB). We observed that NA inhibits the large
      glutamatergic EPSC, evoked by afferent fiber stimulation, in a dose-dependent
      manner. The inhibition was maximal (approximately 48%) at the concentration of 2
      microM. It was antagonized by yohimbine and mimicked by the alpha2-adrenergic
      specific agonist UK14304. Both AMPA and NMDA receptor-mediated EPSCs were
      inhibited in parallel by NA, suggesting a presynaptic effect. Presynaptic
      recordings showed that NA inhibits the action potential (AP) generated Ca current
      by about 20%; however, NA did not significantly affect the presynaptic AP
      waveform. We thus conclude that the calyx of Held presynaptic terminal expresses
      alpha2-adrenergic receptors that inhibit its Ca current and thus glutamate
      release. Noradrenaline was effective in all cells tested from postnatal days 6 to
      7 (P6-P7), and thereafter the number of responsive cells diminished, although
      half of the P14 cells tested still had EPSCs that were inhibited by NA. By
      contrast, activation by L-2-amino-5-phosphonovaleric acid-sensitive metabotropic
      glutamate receptors strongly inhibited the EPSCs of all cells tested from P6 to
      P14. The effect of NA on postsynaptic action potential firing was dependent on
      the stimulus frequency. At 10 Hz, NA had no effect on firing probability;
      however, NA helped MNTB cells fire more action potentials during a 100-Hz train
      of stimuli, even though it did not increase the steady-state depressed EPSC,
      because it produced a smaller N-methyl-D-aspartate (NMDA) receptor-activated
      depolarizing plateau. We therefore suggest that the reduction by NA of the first
      few EPSCs in a train leads to a smaller NMDA depolarizing plateau and thus to
      increased firing probability at 100 Hz in young synapses. Surprisingly, the
      inhibition of glutamate release by NA can thus actually increase the excitability
      of MNTB neurons during early postnatal development.

PMID- 11976370
TI  - Mechanisms underlying fictive feeding in aplysia: coupling between a large neuron
      with plateau potentials activity and a spiking neuron.
AB  - The buccal ganglia of Aplysia contain a central pattern generator (CPG) that
      organizes the rhythmic movements of the radula and buccal mass during feeding.
      Many of the cellular and synaptic elements of this CPG have been identified and
      characterized. However, the roles that specific cellular and synaptic properties
      play in generating patterns of activity are not well understood. To examine these
      issues, the present study developed computational models of a portion of this CPG
      and used simulations to investigate processes underlying the initiation of
      patterned activity. Simulations were done with the SNNAP software package. The
      simulated network contained two neurons, B31/B32 and B63. The development of the
      model was guided and constrained by the available current-clamp data that
      describe the properties of these two protraction-phase interneurons B31/B32 and
      B63, which are coupled via electrical and chemical synapses. Several
      configurations of the model were examined. In one configuration, a fast
      excitatory postsynaptic potential (EPSP) from B63 to B31/B32 was implemented in
      combination with an endogenous plateau-like potential in B31/B32. In a second
      configuration, the excitatory synaptic connection from B63 to B31/B32 produced
      both fast and slow EPSPs in B31/B32 and the plateau-like potential was removed
      from B31/B32. Simulations indicated that the former configuration (i.e.,
      electrical and fast chemical coupling in combination with a plateau-like
      potential) gave rise to a circuit that was robust to changes in parameter values
      and stochastic fluctuations, that closely mimicked empirical observations, and
      that was extremely sensitive to inputs controlling the onset of a burst. The
      coupling between the two simulated neurons served to amplify exogenous
      depolarizations via a positive feedback loop and the subthreshold activation of
      the plateau-like potential. Once a burst was initiated, the circuit produced the
      program in an all-or-none fashion. The slow kinetics of the simulated plateau
      like potential played important roles in both initiating and maintaining the
      burst activity. Thus the present study identified cellular and network properties
      that contribute to the ability of the simulated network to integrate information
      over an extended period before a decision is made to initiate a burst of activity
      and suggests that similar mechanisms may operate in the buccal ganglia in
      initiating feeding movements.

PMID- 11976371
TI  - Interaction of dopamine D1 and NMDA receptors mediates acute clozapine
      potentiation of glutamate EPSPs in rat prefrontal cortex.
AB  - The atypical antipsychotic drug clozapine effectively alleviates both negative
      and positive symptoms of schizophrenia via unclear cellular mechanisms. Clozapine
      may modulate both glutamatergic and dopaminergic transmission in the prefrontal
      cortex (PFC) to achieve part of its therapeutic actions. Using whole cell patch
      clamp techniques, current-clamp recordings in layers V-VI pyramidal neurons from
      rat PFC slices showed that stimulation of local afferents (in 2 microM
      bicuculline) evoked mixed [AMPA/kainate and N-methyl-D-aspartate (NMDA)
      receptors] glutamate receptor-mediated excitatory postsynaptic potentials
      (EPSPs). Clozapine (1 microM) potentiated polysynaptically mediated evoked EPSPs
      (V(Hold) = -65 mV), or reversed EPSPs (rEPSP, V(Hold) = +20 mV) for >30 min. The
      potentiated EPSPs or rEPSPs were attenuated by elevating [Ca(2+)](O) (7 mM), by
      application of NMDA receptor antagonist 2-amino5-phosphonovaleric acid (50
      microM), or by pretreatment with dopamine D1/D5 receptor antagonist SCH23390 (1
      microM) but could be further enhanced by a dopamine reuptake inhibitor bupropion
      (1 microM). Clozapine had no significant effect on pharmacologically isolated
      evoked NMDA-rEPSP or AMPA-rEPSPs but increased spontaneous EPSPs without changing
      the steady-state resting membrane potential. Under voltage clamp, clozapine (1
      microM) enhanced the frequency, and the number of low-amplitude (5-10 pA) AMPA
      receptor-mediated spontaneous EPSCs, while there was no such changes with the
      mini-EPSCs (in 1 microM TTX). Taken together these data suggest that acute
      clozapine can increase spike-dependent presynaptic release of glutamate and
      dopamine. The glutamate stimulates distal dendritic AMPA receptors to increase
      spontaneous EPSCs and enabled a voltage-dependent activation of neuronal NMDA
      receptors. The dopamine released stimulates postsynaptic D1 receptor to modulate
      a lasting potentiation of the NMDA receptor component of the glutamatergic
      synaptic responses in the PFC neuronal network. This sequence of early synaptic
      events induced by acute clozapine may comprise part of the activity that leads to
      later cognitive improvement in schizophrenia.

PMID- 11976372
TI  - Vestibuloocular reflex signal modulation during voluntary and passive head
      movements.
AB  - The vestibuloocular reflex (VOR) effectively stabilizes the visual world on the
      retina over the wide range of head movements generated during daily activities by
      producing an eye movement of equal and opposite amplitude to the motion of the
      head. Although an intact VOR is essential for stabilizing gaze during walking and
      running, it can be counterproductive during certain voluntary behaviors. For
      example, primates use rapid coordinated movements of the eyes and head (gaze
      shifts) to redirect the visual axis from one target of interest to another.
      During these self-generated head movements, a fully functional VOR would generate
      an eye-movement command in the direction opposite to that of the intended shift
      in gaze. Here, we have investigated how the VOR pathways process vestibular
      information across a wide range of behaviors in which head movements were either
      externally applied and/or self-generated and in which the gaze goal was
      systematically varied (i.e., stabilize vs. redirect). VOR interneurons [i.e.,
      type I position-vestibular-pause (PVP) neurons] were characterized during head
      restrained passive whole-body rotation, passive head-on-body rotation, active eye
      head gaze shifts, active eye-head gaze pursuit, self-generated whole-body motion,
      and active head-on-body motion made while the monkey was passively rotated. We
      found that regardless of the stimulation condition, type I PVP neuron responses
      to head motion were comparable whenever the monkey stabilized its gaze. In
      contrast, whenever the monkey redirected its gaze, type I PVP neurons were
      significantly less responsive to head velocity. We also performed a comparable
      analysis of type II PVP neurons, which are likely to contribute indirectly to the
      VOR, and found that they generally behaved in a quantitatively similar manner.
      Thus our findings support the hypothesis that the activity of the VOR pathways is
      reduced "on-line" whenever the current behavioral goal is to redirect gaze. By
      characterizing neuronal responses during a variety of experimental conditions, we
      were also able to determine which inputs contribute to the differential
      processing of head-velocity information by PVP neurons. We show that neither neck
      proprioceptive inputs, an efference copy of neck motor commands nor the monkey's
      knowledge of its self-motion influence the activity of PVP neurons per se. Rather
      we propose that efference copies of oculomotor/gaze commands are responsible for
      the behaviorally dependent modulation of PVP neurons (and by extension for
      modulation of the status of the VOR) during gaze redirection.

PMID- 11976373
TI  - Learning-induced enhancement of postsynaptic potentials in pyramidal neurons.
AB  - We studied the effect of olfactory learning-induced modifications in piriform
      (olfactory) cortex pyramidal neurons on the propagation of postsynaptic
      potentials (PSPs). Rats were trained to distinguish between odors in pairs, in an
      olfactory discrimination task. Three days after training completion, PSPs were
      evoked in layer II pyramidal cells in piriform cortex brain slices by electrical
      stimulation of two pathways. Stimulation of layer Ib activated the intra-cortical
      fibers that terminate on the proximal region of the apical and basal dendrites.
      Stimulation of layer Ia activated the afferent axons that originate from the
      olfactory bulb and terminate on the distal apical dendrites. We have previously
      shown that olfactory training is accompanied by enhanced synaptic transmission in
      the intrinsic pathway, but not in the afferent pathway at 3 days after training.
      Here we show that at this stage, in both pathways PSPs evoked in neurons from
      trained rats had significantly faster rise time measured at the soma compared
      with PSPs in neurons from pseudo-trained and naive rats. Activation of the slow
      afterhyperpolarization (AHP), which is generated by potassium channels probably
      located at the proximal region of both apical and basal dendrites, reduced the
      amplitude measured at the soma of the proximal intrinsic pathway PSPs more
      effectively than PSPs that were generated distally by the afferent fibers. Thus
      the amount of reduction by AHP was used as a measure for the relative distance of
      PSP-generating sites from the soma. In neurons from trained rats, despite the
      previously reported reduction in AHP amplitude, AHP conductance shunted the PSPs
      from both synaptic pathways more efficiently compared with neurons from the
      control rats. We suggest that in neurons from trained rats PSPs are
      electrotonicly closer to the soma.

PMID- 11976374
TI  - Identification of mechanoafferent neurons in terrestrial snail: response
      properties and synaptic connections.
AB  - In this study, we describe the putative mechanosensory neurons, which are
      involved in the control of avoidance behavior of the terrestrial snail Helix
      lucorum. These neurons, which were termed pleural ventrolateral (PlVL) neurons,
      mediated part of the withdrawal response of the animal via activation of the
      withdrawal interneurons. Between 15 and 30 pleural mechanosensory neurons were
      located on the ventrolateral side of each pleural ganglion. Intracellular
      injection of neurobiotin revealed that all PlVL neurons sent their axons into the
      skin nerves. The PlVL neurons had no spontaneous spike activity or fast synaptic
      potentials. In the reduced "CNS-foot" preparations, mechanical stimulation of the
      skin covering the dorsal surface of the foot elicited spikes in the PlVL neurons
      without any noticeable prepotential activity. Mechanical stimulus-induced action
      potentials in these cells persisted in the presence of high-Mg(2+)/zero-Ca(2+)
      saline. Each neuron had oval-shaped receptive field 5-20 mm in length located on
      the dorsal surface of the foot. Partial overlapping of the receptive fields of
      different neurons was observed. Intracellular stimulation of the PlVL neurons
      produced excitatory inputs to the parietal and pleural withdrawal interneurons,
      which are known to control avoidance behavior. The excitatory postsynaptic
      potentials (EPSPs) in the withdrawal interneurons were induced in 1:1 ratio to
      the PlVL neuron spikes, and spike-EPSP latency was short and highly stable. These
      EPSPs also persisted in the high-Mg(2+)/high-Ca(2+) saline, suggesting
      monosynaptic connections. All these data suggest that PlVL cells were the primary
      mechanosensory neurons.

PMID- 11976375
TI  - Quantification of gastric mill network effects on a movement related parameter of
      pyloric network output in the lobster.
AB  - It has long been known that gastric mill network activity (cycle period 5-10 s)
      alters pyloric network output (cycle period approximately 1 s), but these effects
      have not been quantified. Many pyloric muscles extract gastric mill timed
      variations in pyloric motor neuron firing, and consequently produce gastric mill
      timed movements even though no gastric mill neurons innervate them. Determining
      pyloric behavior therefore requires detailed description of gastric mill effects
      on pyloric neural output. Pyloric muscle activity correlates well with motor
      neuron overall spike frequency (OSF, burst spike number divided by cycle period).
      We quantified OSF variation of all pyloric neurons as a function of time into the
      gastric mill cycle [as measured from the beginning of Gastric Mill (GM) neuron
      bursts] in the lobster, Panulirus interruptus. No repeating pattern within
      individual gastric mill cycles of Lateral Pyloric (LP) and Ventricular Dilator
      (VD) neuron OSF was visually apparent. Averaged data showed that VD and LP neuron
      OSF decreased (approximately 0.5 and 1.5 Hz, respectively) at the beginning of
      each gastric mill cycle. Visually apparent patterns of OSF waxing and waning
      within each gastric mill cycle were present for the Inferior Cardiac (IC),
      Pyloric Dilator (PD), and Pyloric (PY) neurons. However, when averaged as a
      function of phase or delay in the gastric mill cycle, the average changes were
      smaller than those in individual gastric mill cycles because when the OSF
      variations occurred varied considerably in different gastric mill cycles. We
      therefore used a "pattern-based" analysis in which an identifying characteristic
      of each neuron's repeating OSF variation pattern was defined as pattern pyloric
      cycle zero. The pyloric cycles in each repetition of the OSF variation pattern
      were numbered relative to the zero cycle, and averaged to create an average OSF
      variation profile. The zero cycle delays relative to GM neuron burst beginning
      were then averaged to determine when in the gastric mill cycle the profile
      occurred. This technique preserved the full extent of pyloric neuron OSF changes.
      Maximum PY neuron OSF occurred within the GM neuron burst, whereas maximum IC and
      PD neuron OSF occurred during the GM neuron interburst interval. Despite these
      changes, pyloric cycling did not phase lock with gastric mill activity, nor were
      an integer number of pyloric cycles present in each gastric mill cycle. In
      addition to providing data necessary to predict pyloric movement, this work shows
      how pattern-based analysis can successfully quantify interactions between
      nonphase-locked networks.

PMID- 11976376
TI  - Long-term potentiation in the rat hippocampus is reversibly depressed by chronic
      intermittent ethanol exposure.
AB  - Alcohol exposure induces multiple neuroadaptive changes in the CNS that can have
      serious long-term consequences on CNS function including cognitive effects and
      attenuation of learning and memory. The cellular mechanisms underlying the CNS
      effects of alcohol have yet to be fully elucidated and are likely to depend on
      the pattern and dose of alcohol exposure. Using electrophysiological recordings
      from hippocampal slices obtained from control and chronic alcohol-treated rats,
      we have investigated the effects of a binge pattern of alcohol abuse on synaptic
      plasticity in the CNS. The alcohol-treated animals were exposed to ethanol vapor
      for 12-14 days using an intermittent exposure paradigm (14 h ethanol exposure/10
      h ethanol withdrawal daily; blood alcohol levels approximately 180 mg/dl), a
      paradigm that models human binge alcohol use. Induction of long-term potentiation
      (LTP) in the CA1 region of the hippocampus by tetanic stimulation of Schaffer
      collaterals was completely blocked in slices from the chronic alcohol-treated
      animals. LTP remained blocked 1 day after withdrawal of animals from alcohol,
      indicating that the neuroadaptive changes produced by alcohol were not readily
      reversible. Partial recovery was observed after withdrawal from alcohol for 5
      days. Other measures of synaptic plasticity including posttetanic potentiation
      and paired-pulse facilitation were also altered by the intermittent alcohol
      treatment paradigm. The results suggest that alterations in synaptic plasticity
      induced by chronic intermittent ethanol consumption play an important role in the
      effects of binge alcohol use on learning and memory function.

PMID- 11976377
TI  - Postnatal changes in membrane properties of mice trigeminal ganglion neurons.
AB  - Intracellular recordings from neurons in the mouse trigeminal ganglion (TG) in
      vitro were used to characterize changes in membrane properties that take place
      from early postnatal stages (P0-P7) to adulthood (>P21). All neonatal TG neurons
      had uniformly slow conduction velocities, whereas adult neurons could be
      separated according to their conduction velocity into Adelta and C neurons. Based
      on the presence or absence of a marked inflection or hump in the repolarization
      phase of the action potential (AP), neonatal neurons were divided into S- (slow)
      and F-type (fast) neurons. Their passive and subthreshold properties (resting
      membrane potential, input resistance, membrane capacitance, and inward
      rectification) were nearly identical, but they showed marked differences in AP
      amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP
      repolarization, and afterhyperpolarization (AHP) duration. Adult TG neurons also
      segregated into S- and F-type groups. Differences in their mean AP amplitude, AP
      overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and
      AHP duration were also prominent. In addition, axons of 90% of F-type neurons and
      60% of S-type neurons became faster conducting in their central and peripheral
      branch, suggestive of axonal myelination. The proportion of S- and F-type neurons
      did not vary during postnatal development, suggesting that these phenotypes were
      established early in development. Membrane properties of both types of TG neurons
      evolved differently during postnatal development. The nature of many of these
      changes was linked to the process of myelination. Thus myelination was
      accompanied by a decrease in AP duration, input resistance (R(in)), and increase
      in membrane capacitance (C). These properties remained constant in unmyelinated
      neurons (both F- and S-type). In adult TG, all F-type neurons with inward
      rectification were also fast-conducting Adelta, suggesting that those F-type
      neurons showing inward rectification at birth will evolve to F-type Adelta
      neurons with age. The percentage of F-type neurons showing inward rectification
      also increased with age. Both F- and S-type neurons displayed changes in the
      sensitivity of the AP to reductions in extracellular Ca(2+) or substitution with
      Co(2+) during the process of maturation.

PMID- 11976378
TI  - Long-term alteration of S-type potassium current and passive membrane properties
      in aplysia sensory neurons following axotomy.
AB  - In many neurons, axotomy triggers long-lasting alterations in excitability as
      well as regenerative growth. We have investigated mechanisms contributing to the
      expression of axotomy-induced, long-term hyperexcitability (LTH) of
      mechanosensory neurons in Aplysia californica. Electrophysiological tests were
      applied to pleural sensory neurons 5-10 days after unilateral crush of pedal
      nerves. Two-electrode current-clamp experiments revealed that compared with
      uninjured sensory neurons on the contralateral side of the body, axotomized
      sensory neurons consistently displayed alterations of passive membrane
      properties: notably, increases in input resistance (R(in)), membrane time
      constant (tau), and apparent input capacitance. In some cells, axotomy also
      depolarized the resting membrane potential (RMP). Axotomized sensory neurons
      showed a lower incidence of voltage relaxation ("sag") during prolonged
      hyperpolarizing pulses and greater depolarizations during long (2 s) but not
      brief (20 ms) pulses. In addition to a reduction in spike accommodation,
      axotomized sensory neurons displayed a dramatic decrease in current (rheobase)
      required to reach spike threshold during long depolarizations. The increase in
      tau was associated with prolongation of responses to brief current pulses and
      with a large increase in the latency to spike at rheobase. Two-electrode voltage
      clamp revealed an axotomy-induced decrease in a current with two components: a
      leakage current component and a slowly activating, noninactivating outward
      current component. Neither component was blocked by agents known to block other
      K(+) currents in these neurons. In contrast to the instantaneous leakage current
      seen with hyperpolarizing and depolarizing steps, the late component of the
      axotomy-sensitive outward current showed a relatively steep voltage dependence
      with pulses to V(m) > -40 mV. These features match those of the S-type
      ("serotonin-sensitive") K(+) current, I(K,S). The close resemblance of I(K,S) to
      a background current mediated by TREK-1 (KCNK2) channels in mammals, raises
      interesting questions about alterations of this family of channels during axotomy
      induced LTH in both Aplysia and mammals. The increase in apparent C(in) may be a
      consequence of the extensive sprouting that has been observed in axotomized
      sensory neurons near their somata, and the decrease in I(K,S) probably helps to
      compensate for the decrease in excitability that would otherwise occur as new
      growth causes both cell volume and C(in) to increase. In peripheral regions of
      the sensory neuron, a decrease in I(K,S) might enhance the safety factor for
      conduction across regenerating segments that are highly susceptible to conduction
      block.

PMID- 11976379
TI  - Missing lateral rectus force and absence of medial rectus co-contraction in
      ocular convergence.
AB  - For a given position of the eye in the orbit, most abducens motoneurons (LRMNs)
      fire at higher rates in converged gaze than when convergence is relaxed, implying
      that lateral rectus (LR) muscle force will be higher for a given eye position in
      convergence. If medial rectus (MR) muscle force balances LR force, it too would
      be higher in convergence, that is, LRMN recording studies predict horizontal
      rectus co-contraction in convergence. Three trained rhesus monkeys with binocular
      eye coils and custom muscle force transducers (MFTs) on LR and MR of one eye
      alternately fixated near (approximately 7 cm) and far (200 cm) targets with
      vergence movements of 20-30 degrees. Tonic muscle forces were also measured
      during conjugate fixation of far targets over a 30 x 30 degrees field. MFT
      characteristics and effects on oculomotility were assessed. Contrary to
      predictions, we found small (<1 g) decreases in both LR and MR forces in
      convergence, for those gaze positions that were used in the brain stem recording
      studies. This missing LR force paradox (higher LRMN firing rates in convergence
      but lower LR forces) suggests that motoneurons or muscle fibers contribute
      differently to oculorotary forces in converged and unconverged states, violating
      the final common path hypothesis. The absence of MR co-contraction is consistent
      with, and supports, the missing LR force finding. Resolution of the missing LR
      force paradox might involve nonlinear interactions among muscle fibers,
      mechanical specialization of muscle fibers and other articulations of the
      peripheral oculomotor apparatus, or extranuclear contributions to muscle
      innervation.

PMID- 11976381
TI  - Impairment of hippocampal CA1 heterosynaptic transformation and spatial memory by
      beta-amyloid(25-35).
AB  - In Alzheimer's disease, the cholinergic damage (reduced neurotransmission) and
      cognitive impairment occur long before beta-amyloid (Abeta) plaque formation. It
      has not been established whether the link between soluble Abeta and cholinergic
      functions contributes to synaptic dysfunction that underlies the cognitive
      impairment. Here, we report that Abeta(25-35), an active form of Abeta, inhibited
      long-term synaptic modification that depends on the associative activation of
      cholinergic and GABAergic inputs when bilaterally injected
      intracerebroventricularly (icv; 200 microg/site). The Abeta microinjections did
      not affect single-pulse-evoked glutamatergic and GABAergic synaptic transmission
      onto the hippocampal CA1 pyramidal cells, while cholinergic intracellular theta;
      was dramatically reduced by the Abeta(25-35) injection. Spatial memory of the
      water maze task was also impaired by the bilateral icv Abeta(25-35) injections,
      while bilateral microinjections of the same dose of Abeta(35-25) was ineffective
      in affecting the long-term synaptic modification evoked by associative activation
      of cholinergic and GABAergic inputs, the cholinergic intracellular theta;, or
      producing memory impairments. Thus restoring the synaptic plasticity involved in
      this associative activation of cholinergic and GABAergic inputs may offer an
      important therapeutic target in the treatment of early Abeta-induced memory
      decline.

PMID- 11976380
TI  - Controlling the statistics of action: obstacle avoidance.
AB  - Task optimization in the presence of signal-dependent noise (TOPS) has been
      proposed as a general framework for planning goal-directed movements. Within this
      framework, the motor command is assumed to be corrupted by signal-dependent
      noise, which leads to a distribution of possible movements. A task can then be
      equated with optimizing some function of the statistics of this distribution. We
      found the optimal trajectory for obstacle avoidance by minimizing the mean
      squared error at the end of the movement while keeping the probability of
      collision with the obstacle below a fixed limit. The optimal paths accurately
      predicted the empirical trajectories. This demonstrates that controlling the
      statistics of movements in the presence of signal-dependent noise may be a
      fundamental and unifying principle of goal-directed movements.

PMID- 11976382
TI  - Dynamically interacting processes underlie synaptic plasticity in a feedback
      pathway.
AB  - Descending feedback is a common feature of sensory systems. Characterizing
      synaptic plasticity in feedback inputs is essential for delineating the role of
      feedback in sensory processing. In this study, we demonstrate that multiple
      interacting processes underlie the dynamics of synaptic potentiation in one such
      sensory feedback pathway. We use field recording and modeling to investigate the
      interaction between the transient high-magnitude potentiation (200-300%) elicited
      during tetanic stimulation of the feedback pathway and the lower magnitude
      posttetanic potentiation (PTP; ~30%) that slowly decays on cessation of the
      tetanus. The amplitude of the observed transient potentiation is graded with
      stimulus frequency. In contrast, the induction of PTP has a stimulus frequency
      threshold between 1 and 5 Hz, and its amplitude is independent of stimulus
      frequency. We suggest that the threshold for PTP induction may be linked to a
      minimum level of sustained potentiation (MSP) during repetitive trains of
      stimuli. We have developed a novel model that describes the interaction between
      the transient plasticity observed during train stimulation and the generation of
      PTP. The model combines a multiplicative, facilitation-depression-type (FD) model
      that describes the transient plasticity, with an enzymatic network that describes
      the dynamics of PTP. The model links transient plasticity to PTP through an input
      term that reflects MSP. The stratum fibrosum-pyramidal cell (StF-PC) synapse
      investigated in this study is the terminus of a feedback pathway to the
      electrosensory lateral line lobe (ELL) of a weakly electric gymnotiform fish.
      Dynamic plasticity at the StF-PC synapse may contribute to the putative role of
      this feedback pathway as a sensory searchlight.

PMID- 11976383
TI  - Chronic morphine treatment alters endogenous opioid control of hippocampal mossy
      fiber synaptic transmission.
AB  - Synaptic adaptations are thought to be an important component of the consequences
      of drug abuse. One such adaptation is an up-regulation of adenylyl cyclase that
      has been shown to increase transmitter release at several inhibitory synapses. In
      this study the effects of chronic morphine treatment were studied on mossy fiber
      synapses in the guinea pig hippocampus using extracellular field potential
      recordings. This opioid-sensitive synapse was chosen because of the known role of
      the adenylyl cyclase cascade in the regulation of glutamate release. Long-term
      potentiation (LTP) at the mossy fiber synapse was enhanced after chronic morphine
      treatment. In control animals, opioid antagonists increased LTP but had no effect
      in morphine-treated guinea pigs. In contrast, the long-lasting depression of
      transmission induced by a mGluR agonist and CA1 LTP were not altered. Chronic
      morphine treatment neither caused tolerance to mu- and kappa-receptor-mediated
      inhibition at the mossy fiber synapse nor modified total hippocampal dynorphin
      levels. The results suggest that the phasic inhibition of glutamate transmission
      mediated by endogenous opioids is reduced after chronic exposure to morphine.

PMID- 11976384
TI  - Layer I ectopias and increased excitability in murine neocortex.
AB  - Cortical dysplasias are associated with both epilepsy and cognitive impairments
      in humans. Similarly, several animal models of cortical dysplasia show that
      dysplasia causes increased seizure susceptibility and behavioral deficits in vivo
      and increased levels of excitability in vitro. As most current animal models
      involve either global disruptions in cortical architecture or the induction of
      lesions, it is not yet clear whether small spontaneous neocortical malformations
      are also associated with increased excitability or seizure susceptibility. Small
      groups of displaced neurons in layer I of the neocortex, ectopias, have been
      identified in patients with cognitive impairments, and similar malformations
      occur sporadically in some inbred lines of mice where they are associated with
      behavioral and sensory-processing deficits. In a previous study, we characterized
      the physiology of cells within neocortical ectopias, in one of the inbred lines
      (NXSM-D/Ei) and showed that the presence of multiple ectopias is associated with
      the generation of spontaneous epileptiform activity in slices. In this study, we
      use extracellular recordings from brain slices to show that even single-layer I
      ectopias are associated with higher excitability. Specifically, slices that
      contain single ectopias display epileptiform activity at significantly lower
      concentrations of the GABA(A) receptor antagonist bicuculline than do slices
      without ectopias (either from opposite hemispheres or animals without ectopias).
      Moreover, because removal of ectopias from slices does not restore normal
      excitability, enhanced excitability is not generated within the ectopia. Finally,
      we show that in vivo, mice with ectopias are more sensitive to the convulsant
      pentylenetetrazole than are mice without ectopias. Together these results suggest
      that alterations in cortical hemispheres containing focal layer I malformations
      increase cortical excitability and that even moderately small spontaneous
      cortical dysplasias are associated with increased excitability in vitro and in
      vivo.

PMID- 11976385
TI  - Muscle tone facilitation and inhibition after orexin-a (hypocretin-1)
      microinjections into the medial medulla.
AB  - Orexins/hypocretins are synthesized in neurons of the perifornical, dorsomedial,
      lateral, and posterior hypothalamus. A loss of hypocretin neurons has been found
      in human narcolepsy, which is characterized by sudden loss of muscle tone, called
      cataplexy, and sleepiness. The normal functional role of these neurons, however,
      is unclear. The medioventral medullary region, including gigantocellular
      reticular nucleus, alpha (GiA) and ventral (GiV) parts, participates in the
      induction of locomotion and muscle tone facilitation in decerebrate animals and
      receives moderate orexinergic innervation. In the present study, we have examined
      the role of orexin-A (OX-A) in muscle tone control using microinjections (50
      microM, 0.3 microl) into the GiA and GiV sites in decerebrate rats. OX-A
      microinjections into GiA sites, previously identified by electrical stimulation
      as facilitating hindlimb muscle tone bilaterally, produced a bilateral increase
      of muscle tone in the same muscles. Bilateral lidocaine microinjections (4%, 0.3
      microl) into the dorsolateral mesopontine reticular formation decreased muscle
      rigidity and blocked muscle tone facilitation produced by OX-A microinjections
      into the GiA sites. The activity of cells related to muscle rigidity, located in
      the pedunculopontine tegmental nucleus and adjacent reticular formation, was
      correlated positively with the extent of hindlimb muscle tone facilitation after
      medullary OX-A microinjections. OX-A microinjections into GiV sites were less
      effective in muscle tone facilitation, although these sites produced a muscle
      tone increase during electrical stimulation. In contrast, OX-A microinjections
      into the gigantocellular nucleus (Gi) sites and dorsal paragigantocellular
      nucleus (DPGi) sites, previously identified by electrical stimulation as
      inhibitory points, produced bilateral hindlimb muscle atonia. We propose that the
      medioventral medullary region is one of the brain stem target for OX-A modulation
      of muscle tone. Facilitation of muscle tone after OX-A microinjections into this
      region is linked to activation of intrinsic reticular cells, causing excitation
      of midbrain and pontine neurons participating in muscle tone facilitation through
      an ascending pathway. Moreover, our results suggest that OX-A may also regulate
      the activity of medullary neurons participating in muscle tone suppression. Loss
      of OX function may, therefore, disturb both muscle tone facilitatory and
      inhibitory processes at the medullary level.

PMID- 11976386
TI  - Stimulation of 5-HT(2) receptors in prefrontal pyramidal neurons inhibits
      Ca(v)1.2 L type Ca(2+) currents via a PLCbeta/IP3/calcineurin signaling cascade.
AB  - There is growing evidence linking alterations in serotonergic signaling in the
      prefrontal cortex to the etiology of schizophrenia. Prefrontal pyramidal neurons
      are richly innervated by serotonergic fibers and express high levels of
      serotonergic 5-HT(2)-class receptors. It is unclear, however, how activation of
      these receptors modulates cellular activity. To help fill this gap, whole cell
      voltage-clamp and single-cell RT-PCR studies of acutely isolated layer V-VI
      prefrontal pyramidal neurons were undertaken. The vast majority (>80%) of these
      neurons had detectable levels of 5-HT(2A) or 5-HT(2C) receptor mRNA. Bath
      application of 5-HT(2) agonists inhibited voltage-dependent Ca(2+) channel
      currents. L-type Ca(2+) channels were a particularly prominent target of this
      signaling pathway. The L-type channel modulation was blocked by disruption of
      G(alphaq) signaling or by inhibition of phospholipase Cbeta. Antagonism of
      intracellular inositol trisphosphate signaling, chelation of intracellular
      Ca(2+), or depletion of intracellular Ca(2+) stores also blocked this modulation.
      Inhibition of the Ca(2+)-dependent phosphatase calcineurin prevented receptor
      mediated modulation of L-type currents. Last, the 5-HT(2) receptor modulation was
      robustly expressed in neurons from Ca(v)1.3 knockout mice. These findings argue
      that 5-HT(2) receptors couple through G(alphaq) proteins to trigger a
      phospholipase Cbeta/inositol trisphosphate signaling cascade resulting in the
      mobilization of intracellular Ca(2+), activation of calcineurin, and inhibition
      of Ca(v)1.2 L-type Ca(2+) currents. This modulation and its blockade by atypical
      neuroleptics could have wide-ranging effects on synaptic integration and long
      term gene expression in deep-layer prefrontal pyramidal neurons.

PMID- 11976387
TI  - Intracellularly labeled fusiform cells in dorsal cochlear nucleus of the gerbil.
      I. Physiological response properties.
AB  - Fusiform cells in the dorsal cochlear nucleus (DCN) of barbiturate-anesthetized
      Mongolian gerbils were characterized physiologically and labeled with
      neurobiotin. This report is based on 17 fusiform cells for which there was
      reasonable confidence in the association between physiological data and recovered
      anatomy. The qualitative morphology of these cells was no different from that
      reported in previous studies. The acoustic response properties were generally
      consistent with those described in the barbiturate-anesthetized cat. Most
      responses were of the pauser or buildup type, but a dependence on stimulus
      frequency and intensity was observed. Stimulus-evoked sustained depolarizations
      and large, long-lasting afterhyperpolarizations were common membrane potential
      features. The cells in this study showed a greater tendency to discharge
      regularly than did those of the cat, likely as a result of the longer
      interstimulus interval used. Barbiturate anesthesia appears to mask an
      interspecies difference in DCN physiology that is apparent in unanesthetized,
      decerebrate preparations. The response of these fusiform cells to a depolarizing
      current pulse could be altered by the presence of a hyperpolarizing prepulse.
      Buildup, pauser, and chopper patterns could each be created using appropriate
      combinations of hyperpolarizing and depolarizing pulse amplitudes. Thus the adult
      gerbil appears to express the inactivating potassium conductance previously shown
      to affect fusiform cell firing patterns in vitro. The results further demonstrate
      that the effects of these potassium currents are readily observed in vivo.
      Finally, the fusiform cells in this study were quite variable with respect to a
      number of response properties, including the resting potential, input resistance,
      spontaneous activity, relative noise index, normalized tone slope, and regularity
      histogram shape. This diversity likely results from cell-to-cell variations in
      the balance of activity within the relatively complex network to which the
      fusiform cells belong, although effects of impalement may contribute to the
      extent of the diversity.

PMID- 11976388
TI  - Intracellularly labeled fusiform cells in dorsal cochlear nucleus of the gerbil.
      II. Comparison of physiology and anatomy.
AB  - Fusiform cells represent the major class of dorsal cochlear nucleus (DCN)
      projection neuron. Although much is understood about their physiology and
      anatomy, there remain unexplored issues with important functional implications.
      These include interspecies differences in DCN physiology and the nature of the
      cell-to-cell variations in fusiform cell physiology. To address these issues, a
      quantitative examination was made of the physiology and anatomy of 17 fusiform
      cells from a companion study. The results suggest that the basal dendrites of
      gerbil fusiform cells may be electrotonically more compact than those of the cat.
      This relative decrease in the filtering of excitatory inputs might account for
      the lower incidence of type IV units in that species. These data also suggest
      that the gerbil DCN lacks the high-frequency specialization described in the cat,
      because the tonotopic arrangement of the gerbil fusiform cells quantitatively
      matches the place-frequency map for the gerbil cochlea. Certain physiological
      properties have anatomical correlates. First, the basal dendrites of low
      spontaneous rate cells are directed away from the soma only in the caudal
      direction, while the high spontaneous rate cells have basal dendrites extending
      rostrally and caudally. Second, input resistance was dominated by the surface
      area of the apical dendrite. Third, the discharge pattern was correlated with
      apical dendrite orientation. Finally, there was a spatial gradient of sensitivity
      to broadband noise organized at least partially within an isofrequency axis. Such
      trends indicate that neighboring fusiform cells are endowed with different signal
      processing capabilities.

PMID- 11976389
TI  - Neuronal activity patterns in primate primary motor cortex related to trained or
      semiautomatic jaw and tongue movements.
AB  - The present study was undertaken to determine the firing patterns and the
      mechanoreceptive field (RF) properties of neurons within the face primary motor
      cortex (face-MI) in relation to chewing and other orofacial movements in the
      awake monkey. Of a total of 107 face-MI neurons recorded, 73 of 74 tested had
      activity related to chewing and 47 of 66 neurons tested showed activity related
      to a trained tongue task. Of the 73 chewing-related neurons, 52 (71.2%) showed
      clear rhythmic activity during rhythmic chewing. A total of 32 (43.8%) also
      showed significant alterations in activity in relation to the swallowing of a
      solid food (apple) bolus. Many of the chewing-related neurons (81.8% of 55
      tested) had an orofacial RF, which for most was on the tongue dorsum. Tongue
      protrusion was evoked by intracortical microstimulation (ICMS) at most (63.6%) of
      the recording sites where neurons fired during the rhythmic jaw-opening phase,
      whereas tongue retraction was evoked by ICMS at most (66.7%) sites at which the
      neurons firing during the rhythmic jaw-closing phase were recorded. Of the 47
      task-related neurons, 21 of 22 (95.5%) examined also showed chewing-related
      activity and 29 (61.7%) demonstrated significant alteration in activity in
      relation to the swallowing of a juice reward. There were no significant
      differences in the peak firing frequency among neuronal activities related to
      chewing, swallowing, or the task. These findings provide further evidence that
      face-MI may play an important role not only in trained orofacial movements but
      also in chewing as well as swallowing, including the control of tongue and jaw
      movements that occur during the masticatory sequence.

PMID- 11976390
TI  - Weakly modulated spike trains: significance, precision, and correction for sample
      size.
AB  - Many single-unit electrophysiological studies of visual cortex have investigated
      strong evoked responses to simple stimuli such as oriented gratings. Experiments
      involving other types of stimuli, such as natural scenes, higher-order features,
      and surface brightness, produce single-unit responses that are more difficult to
      interpret. Experiments with brightness, in particular, evoke single-unit
      responses that are typically weakly modulated. When the brightness is generated
      by a visual illusion such as the Cornsweet illusion, statistical tests are often
      necessary to distinguish true responses from baseline fluctuations. Here, using
      data collected from cat Areas 17 and 18 in response to real and illusory
      brightness stimuli, we provide a method for detecting and quantifying weak but
      significant periodic responses. By randomizing spike trains (via bootstrap
      methods), we provide confidence levels for response significance, permitting the
      evaluation of both weak and strong responses. We show that because of a strong
      dependence on total spike number, response significance can only be appropriately
      determined with randomized spike trains of similar spike number. Such
      randomizations can be performed for both stimulus-elicited and spontaneously
      occurring spike trains. By developing a method for generating randomized
      modulated spike trains (phase-restricted randomization) from actual recordings,
      we calculate upper and lower confidence limits of modulated spike trains and
      describe how measurement precision varies as a function of total spike count.
      Finally, using this randomization method, we describe how a correction function
      can be determined to correct for measurement bias introduced at low spike counts.
      These methods may also be useful in the study of small but potentially
      significant responses in other systems.

PMID- 11976391
TI  - Proton-gated channels in PC12 cells.
AB  - Acid-sensing ion channels (ASICs) are expressed in various sensory and central
      neurons. The functional role of these channels remains elusive. Complex subunit
      combinations and lack of specific blockers for native receptors are likely to
      contribute to the difficulty of resolving the function of ASICs. Finding a
      neuronal cell line, which expresses a single population of ASICs, should prove to
      be useful in delineating the function of individual ASICs. Using patch-clamp,
      Ca(2+)-imaging, and RT-PCR techniques, we have explored the existence of ASICs in
      PC12 cells, a clonal neuronal cell line. Fast drops of extracellular pH activated
      transient inward currents in PC12 cells with pH(0.5) at 6.0-6.2. The ASICs in
      PC12 cells were selective for Na(+) with significant Ca(2+) permeability.
      Currents in PC12 cells were blocked by the nonselective ASIC blocker amiloride.
      PcTX1, a specific homomeric ASIC1a blocker, also blocked the ASIC currents with
      an IC(50) of approximately 1.5 nM. RT-PCR demonstrated the existence of ASIC1a
      transcript in both undifferentiated and nerve growth factor-differentiated PC12
      cells. Our data suggest that PC12 cells likely contain a single population of
      functional proton-gated channel-homomeric ASIC1a. It might be an ideal neuronal
      cell line for the study of physiological and potential pathological roles of this
      key subunit of ASICs.

PMID- 11976392
TI  - Activity-dependent expression of simultaneous glutamatergic and GABAergic
      neurotransmission from the mossy fibers in vitro.
AB  - GABAergic transmission in the mossy fiber (MF) projection of the hippocampus is
      not normally detected in the rat. However, seizures induce simultaneous
      glutamatergic and GABAergic transmission in this projection, which coincides with
      an overexpression of GAD(67) and vesicular GABA transporter (VGAT) mRNA in the
      dentate gyrus (DG) and MF. To test whether this plastic change could be induced
      in an activity-dependent fashion in the absence of seizures, I recorded
      intracellularly from slices/cells that served as their own control, before and
      after direct or synaptic kindling of the DG in vitro. As expected, synaptic
      responses of CA3 pyramidal cells to test pulse DG stimulation were blocked by
      perfusion of N-methyl-D-aspartate (NMDA) and non-NMDA receptors' antagonists.
      However, after kindling the perforant path (3 1-s trains of 0.1-ms pulses at 100
      Hz, 1 min apart from each other every 15 min for 3 h), which potentiated synaptic
      responses without inducing epileptiform activity, the perfusion of glutamatergic
      antagonists blocked the excitatory synaptic potential and isolated a fast
      bicuculline-sensitive inhibitory synaptic potential. Immunohistochemical
      experiments confirmed the overexpression of GAD(67) in the kindled slices. If
      kindling stimulation was provided just for 1 h or if it was completed in the
      presence of the protein synthesis inhibitor, cycloheximide, the expression of the
      GABAergic potential was prevented. Alternatively, when control synaptic responses
      of a given cell were first blocked, the direct kindling stimulation over the same
      site during perfusion of glutamatergic antagonists resulted in the induction of
      fast GABAergic potentials after 16.6 +/- 0.9 kindling trials. Furthermore, a high
      spacial specificity of this phenomenon was evidenced by recording synaptic
      responses of a given pyramidal cell to two different MF inputs. After blockade of
      all synaptic responses with the perfusion of glutamatergic antagonists, one of
      the inputs was kindled, while synaptic responses between the kindling trials were
      monitored by applying test pulse stimulation to both inputs. After 17 +/- 1
      trials, test pulse stimulation provided over the kindled site evoked GABAergic
      potentials, whereas test pulse stimulation delivered to the alternative
      nonkindled parallel MF input remained ineffective. The DG-evoked GABAergic
      responses were inhibited by the activation of GABA(B)R and mGluR, whereby
      activation of group III mGluR with L-2-amino-4-phosphonobutyric acid (L-AP4) was
      significantly more effective than the activation of group II mGluR with DCG-IV.
      These data demonstrate that GABAergic transmission from the MF projection has
      distinctive features in the adult rat, and that its induction is dependent on
      protein synthesis responding in an activity-dependent fashion.

PMID- 11976393
TI  - Inhibitory interactions between ferret thalamic reticular neurons.
AB  - The thalamic reticular nucleus (nRt) provides an important inhibitory input to
      thalamic relay nuclei and is central in the generation of both normal and
      abnormal thalamocortical activities. Although local inhibitory interactions
      between these neurons may play an important role in controlling thalamocortical
      activities, the physiological features of this interaction have not been fully
      investigated. Here we sought to establish the nature of inhibitory interaction
      between nRt neurons with intracellular and extracellular recordings in slices of
      ferret nRt maintained in vitro. In many nRt neurons, intracellular recordings
      revealed spontaneous inhibitory postsynaptic potentials (IPSPs). In addition, the
      local excitation of nRt cells with glutamate led to the generation of IPSPs in
      the intracellularly recorded nRt neuron. These evoked IPSPs exhibited an average
      reversal potential of -72 mV and could be blocked by picrotoxin, a GABA(A)
      receptor antagonist. These results indicate that nRt neurons interact locally
      through the activation of GABA(A) receptor-mediated inhibitory postsynaptic
      potentials. This lateral inhibition may play an important role in controlling the
      responsiveness of these cells to cortical and thalamic excitatory inputs in both
      normal and abnormal thalamocortical function.

PMID- 11976394
TI  - Role of the human medial frontal cortex in task switching: a combined fMRI and
      TMS study.
AB  - We used event-related functional magnetic resonance imaging (fMRI) to measure
      brain activity when subjects were performing identical tasks in the context of
      either a task-set switch or a continuation of earlier performance. The context,
      i.e., switching or staying with the current task, influenced medial frontal
      cortical activation; the medial frontal cortex is transiently activated at the
      time that subjects switch from one way of performing a task to another. Two types
      of task-set-switching paradigms were investigated. In the response-switching (RS)
      paradigm, subjects switched between different rules for response selection and
      had to choose between competing responses. In the visual-switching (VS) paradigm,
      subjects switched between different rules for stimulus selection and had to
      choose between competing visual stimuli. The type of conflict, sensory (VS) or
      motor (RS), involved in switching was critical in determining medial frontal
      activation. Switching in the RS paradigm was associated with clear blood
      oxygenation-level-dependent signal increases ("activations") in three medial
      frontal areas: the rostral cingulate zone, the caudal cingulate zone, and the
      presupplementary motor area (pre-SMA). Switching in the VS task was associated
      with definite activation in just one medial frontal area, a region on the border
      between the pre-SMA and the SMA. Subsequent to the fMRI session, we used MRI
      guided frameless stereotaxic procedures and repetitive transcranial magnetic
      stimulation (rTMS) to test the importance of the medial frontal activations for
      task switching. Applying rTMS over the pre-SMA disrupted subsequent RS
      performance but only when it was applied in the context of a switch. This result
      shows, first, that the pre-SMA is essential for task switching and second that
      its essential role is transient and limited to just the time of behavioral
      switching. The results are consistent with a role for the pre-SMA in selecting
      between response sets at a superordinate level rather than in selecting
      individual responses. The effect of the rTMS was not simply due to the tactile
      and auditory artifacts associated with each pulse; rTMS over several control
      regions did not selectively disrupt switching. Applying rTMS over the SMA/pre-SMA
      area activated in the VS paradigm did not disrupt switching. This result, first,
      confirms the limited importance of the medial frontal cortex for sensory
      attentional switching. Second, the VS rTMS results suggest that just because an
      area is activated in two paradigms does not mean that it plays the same essential
      role in both cases.

PMID- 11976395
TI  - Properties of the pathways from the lateral amygdal nucleus to basolateral
      nucleus and amygdalostriatal transition area.
AB  - Studies have revealed that the amygdala formation is involved in emotional
      learning, attention, and autonomic functions. Although intra-amygdala connections
      have been described anatomically, the functional characteristics of these
      connections are not well understood. We used a rat brain slice preparation with a
      voltage-sensitive imaging system to compare the electrophysiological
      characteristics of intra-amygdala pathways. Electrical stimuli delivered to the
      lateral nucleus (La) caused the optical signal to propagate to basolateral
      nucleus (BL) and amygdalostriatal transition area (AStr), but not the central
      nucleus (Ce), consistent with previous anatomical studies, including the recently
      characterized projections from La to AStr. The velocity of propagation of the
      evoked potential along the La-AStr pathway was significantly faster than that
      along the La-BL pathway. In addition, the efficiency of the signal transmission
      (determined by the rate of decay) along the La-AStr pathway was higher than that
      along the La-BL pathway. Also, AStr possessed a distinct property of temporal
      summation of La signals. On the other hand, the La-BL pathway possessed a
      significantly higher sensitivity to bicuculline/picrotoxin and a stronger paired
      pulse inhibition than the La-AStr pathway. Furthermore, the La-BL pathway
      expressed a higher D-2-amino-5-phosphonovaleric acid (a NMDA blocker) sensitivity
      than the La-AStr pathway. These results suggest that the La-AStr pathway, which
      conducts signals with high velocity and less attenuation, may be involved in
      rapid reflexive responses during fear-induced behavior, whereas the La-BL pathway
      facilitates signal integration and learning.

PMID- 11976396
TI  - Receptive fields and response properties of neurons in the star-nosed mole's
      somatosensory fovea.
AB  - Star-nosed moles have an extraordinary mechanosensory system consisting of 22
      densely innervated nasal appendages covered with thousands of sensitive touch
      domes. A single appendage acts as the fovea and the star is constantly shifted to
      touch this foveal appendage to objects of interest. Here we investigated the
      receptive fields on the star and the response properties of 144 neurons in the
      mole's primary somatosensory cortex (S1). Excitatory receptive fields were
      defined by recording multiunit activity from the S1 representations of the nasal
      appendages that form the star, while stimulating the touch domes on the skin
      surface with a small probe. Receptive fields were among the smallest reported for
      mammalian glabrous skin, averaging <1 mm(2). The smallest receptive fields were
      found for the fovea representation, corresponding to its greater cortical
      magnification. Single units were then isolated, primarily from the representation
      of the somatosensory fovea, and the skin surface was stimulated with a small
      probe attached to a piezoelectric wafer controlled by a computer interface. The
      response properties of neurons and the locations of inhibitory surrounds were
      evaluated with two complementary approaches. In the first set of experiments,
      single microelectrodes were used to isolate unit activity in S1, and data were
      collected for stimulation to different areas of the sensory star. In the second
      set of experiments, a multi-electrode array (4 electrodes spaced at 200 microm in
      a linear sequence) was used to simultaneously record from isolated units in
      different cortical areas representing different parts of the sensory periphery.
      These experiments revealed a short-latency excitatory discharge to stimulation of
      the fovea followed by a long-lasting suppression of spontaneous activity. Sixty
      one percent of neurons responded with an excitatory OFF response at the end of
      the stimulus; the remaining 39% of cells did not respond or were inhibited at
      stimulus offset. Stimulation of areas surrounding the central receptive field
      often revealed inhibitory surrounds. Forty percent of the neurons that responded
      to mechanosensory stimulation of the receptive field center were inhibited by
      stimulation of surrounding areas of skin on the same appendage. In contrast to
      neurons in rodent barrels, few neurons within a stripe representing an appendage
      responded to stimulation of neighboring (nonprimary) appendages on the snout. The
      small receptive fields, short latencies, and inhibitory surrounds are consistent
      with the star's role in rapidly determining the locations and identities of
      objects in a complex tactile environment.

PMID- 11976397
TI  - Role for G protein Gbetagamma isoform specificity in synaptic signal processing:
      a computational study.
AB  - Computational modeling is used to investigate the functional impact of G protein
      mediated presynaptic autoinhibition on synaptic filtering properties. It is
      demonstrated that this form of autoinhibition, which is relieved by
      depolarization, acts as a high-pass filter. This contrasts with vesicle
      depletion, which acts as a low-pass filter. Model parameters are adjusted to
      reproduce kinetic slowing data from different Gbetagamma dimeric isoforms, which
      produce different degrees of slowing. With these sets of parameter values, we
      demonstrate that the range of frequencies filtered out by the autoinhibition
      varies greatly depending on the Gbetagamma isoform activated by the
      autoreceptors. It is shown that G protein autoinhibition can enhance the spatial
      contrast between a spatially distributed high-frequency signal and surrounding
      low-frequency noise, providing an alternate mechanism to lateral inhibition. It
      is also shown that autoinhibition can increase the fidelity of coincidence
      detection by increasing the signal-to-noise ratio in the postsynaptic cell. The
      filter cut, the input frequency below which signals are filtered, depends on
      several biophysical parameters in addition to those related to Gbetagamma binding
      and unbinding. By varying one such parameter, the rate at which transmitter
      unbinds from autoreceptors, we show that the filter cut can be adjusted up or
      down for several of the Gbetagamma isoforms. This allows for great synapse-to
      synapse variability in the distinction between signal and noise.

PMID- 11976398
TI  - Selective modulation of tonic and phasic inhibitions in dentate gyrus granule
      cells.
AB  - In some nerve cells, activation of GABA(A) receptors by GABA results in phasic
      and tonic conductances. Transient activation of synaptic receptors generates
      phasic inhibition, whereas tonic inhibition originates from GABA acting on
      extrasynaptic receptors, like in cerebellar granule cells, where it is thought to
      result from the activation of extrasynaptic GABA(A) receptors with a specific
      subunit composition (alpha(6)beta(x)delta). Here we show that in adult rat
      hippocampal slices, extracellular GABA levels are sufficiently high to generate a
      powerful tonic inhibition in delta subunit-expressing dentate gyrus granule
      cells. In these cells, the mean tonic current is approximately four times larger
      than that produced by spontaneous synaptic currents occurring at a frequency of
      approximately 10 Hz. Antagonizing the GABA transporter GAT-1 with NO-711 (2.5
      microM) selectively enhanced tonic inhibition by 330% without affecting the
      phasic component. In contrast, by prolonging the decay of inhibitory postsynaptic
      currents (IPSCs), the benzodiazepine agonist zolpidem (0.5 microM) augmented
      phasic inhibition by 66%, while leaving the mean tonic conductance unchanged.
      These results demonstrate that a tonic GABA(A) receptor-mediated conductance can
      be recorded from dentate gyrus granule cells of adult rats in in vitro slice
      preparations. Furthermore, we have identified distinct pharmacological tools to
      selectively modify tonic and phasic inhibitions, allowing future studies to
      investigate their specific roles in neuronal function.

PMID- 11976399
TI  - A new dimension for the development of fluorescence-based assays in solution:
      from physical principles of FCS detection to biological applications.
AB  - Ultrasensitive detection methods such as laser-induced fluorescence represent the
      current state-of-the-art in analytics. Single-molecule detection in solution has
      received a remarkable amount of attention in the last few years because of its
      applicability to life sciences. Studies have been performed on the fundamentals
      of the detection processes themselves and on some biological systems.
      Fluorescence correlation spectroscopy (FCS) is the link for ultrasensitive
      multicomponent analysis, showing possibilities for experiments on molecular
      interactions. Based on the theoretical background of FCS, this article gives full
      explanation of FCS and an update of highlights in experimental biology and
      medicine studied by FCS. We focus on a repertoire of diverse immunoglobulin
      specificities, a ribosome display system, single-molecule DNA sequencing, and a
      mutant enzyme generated by random mutagenesis of amino acids. We describe the
      usefulness and the enormous potential of the methodology. Further, this
      contribution clearly indicates that FCS is a valuable tool for solution-phase
      single-molecule (SPSM) experiments in immunobiology and medicine. In experiments
      with the Goodpasture autoantibody, we worked out conditions for the design of
      experiments on a complex single molecule in solution. The possibility to use SPSM
      FCS as a quantitation methodology opens up other important applications beyond
      the scope of this article. Original results extending the published studies are
      presented for the rational foundation of SPSM-FCS. In this original contribution,
      we deal with experimental systems for biology and medicine where the number of
      molecules in solution is very small. This article is mandatory for gaining
      confidence in the interpretation of experimental SPSM-FCS results on the
      selfsame, individual single molecule in solution.

PMID- 11976400
TI  - Factors involved in the regulation of type I collagen gene expression:
      implication in fibrosis.
AB  - Type I collagen, the major component of extracellular matrix in skin and other
      tissues, is a heterotrimer of two alpha1 and one alpha2 collagen polypeptides.
      The synthesis of both chains is highly regulated by different cytokines at the
      transcriptional level. Excessive synthesis and deposition of collagen in the
      dermal region causes thick and hard skin, a clinical manifestation of
      scleroderma. To better understand the causes of scleroderma or other tissue
      fibrosis, it is very important to investigate the molecular mechanisms that cause
      upregulation of the Type I collagen synthesis in these tissues. Several cis
      acting regulatory elements and trans-acting protein factors, which are involved
      in basal as well as cytokine-modulated Type I collagen gene expression, have been
      identified and characterized. Hypertranscription of Type I collagen in
      scleroderma skin fibroblasts may be due to abnormal activities of different
      positive or negative transcription factors in response to different abnormally
      induced signaling pathways. In this review, I discuss the present day
      understanding about the involvement of different factors in the regulation of
      basal as well as cytokine-modulated Type I collagen gene expression and its
      implication in scleroderma research.

PMID- 11976401
TI  - The GABA(B) antagonist CGP 52432 attenuates the stimulatory effect of the GABA(B)
      agonist SKF 97541 on luteinizing hormone secretion in the male sheep.
AB  - The objectives of this study were to determine if the gamma-aminobutyric acid
      (GABA)(B) agonist, 3-aminopropyl (methyl) phosphinic acid (SKF97541), would
      increase luteinizing hormone (LH) secretion when infused by microdialysis into
      the medial basal hypothalamus (MBH) of the castrated ram, and to determine if the
      action of SKF97541 would be attenuated by co-infusion of the GABA(B) antagonist
      CGP52432. Initial experiments established that infusion of SKF alone, at
      concentrations as low as 5 microM, increased mean LH, LH pulse amplitude, and in
      some cases, pulse interval. In the last experiment, animals were treated with
      artificial cerebrospinal fluid (CSF) alone, SKF alone (30 microM), 3-[[(3, 4
      dichlorophenol) methyl] amino] propyl] diethoxymethyl) phosphinic acid (CGP)
      alone (500 microM), or SKF plus CGP. SKF increased both mean LH and LH pulse
      amplitude as compared with CSF. CGP alone had no significant effect on LH, but it
      attenuated the effect of SKF on mean LH. These observations indicate that the
      stimulatory effects of GABA(B) agonists on LH pulse patterns are mediated through
      GABA(B) receptors and provide further evidence that GABA(B) receptors located in
      the MBH can regulate pulsatile GnRH-LH release.

PMID- 11976402
TI  - Inhibitory effects of cocoa flavanols and procyanidin oligomers on free radical
      induced erythrocyte hemolysis.
AB  - Excessive peroxidation of biomembranes is thought to contribute to the initiation
      and progression of numerous degenerative diseases. The present study examined the
      inhibitory effects of a cocoa extract, individual cocoa flavanols (-)-epicatechin
      and (+)-catechin, and procyanidin oligomers (dimer to decamer) isolated from
      cocoa on rat erythrocyte hemolysis. In vitro, the flavanols and the procyanidin
      oligomers exhibited dose-dependent protection against 2,2'-azo-bis (2
      amidinopropane) dihydrochloride (AAPH)-induced erythrocyte hemolysis between
      concentrations of 2.5 and 40 microM. Dimer, trimer, and tetramer showed the
      strongest inhibitory effects at 10 microM, 59.4%, 66.2%, 70.9%; 20 microM, 84.1%,
      87.6%, 81.0%; and 40 microM, 90.2%, 88.9%, 78.6%, respectively. In a subsequent
      experiment, male Sprague-Dawley rats (approximately 200 g; n = 5-6) were given a
      100-mg intragastric dose of a cocoa extract. Blood was collected over a 4-hr time
      period. Epicatechin and catechin, and the dimers (-)-epicatechin-(4beta>8)
      epicatechin (Dimer B2) and (-)-epicatechin-(4beta>6)-epicatechin (Dimer B5) were
      detected in the plasma with concentrations of 6.4 microM, and 217.6, 248.2, and
      55.4 nM, respectively. Plasma antioxidant capacity (as measured by the total
      antioxidant potential [TRAP] assay) was elevated (P < 0.05) between 30 and 240
      min following the cocoa extract feeding. Erythrocytes obtained from the cocoa
      extract-fed animals showed an enhanced resistance to hemolysis (P < 0.05). This
      enhanced resistance was also observed when erythrocytes from animals fed the
      cocoa extract were mixed with plasma obtained from animals given water only.
      Conversely, plasma obtained from rats given the cocoa extract improved the
      resistance of erythrocytes obtained from rats given water only. These results
      show cocoa flavanols and procyanidins can provide membrane protective effects.

PMID- 11976403
TI  - Release of cytokines by human nasal epithelial cells and peripheral blood
      mononuclear cells infected with Mycoplasma pneumoniae.
AB  - Mycoplasma pneumoniae (Mp) infection is associated with asthma exacerbation in
      children. We hypothesized that Mp infection may cause airway inflammation by
      inducing the release of cytokines by respiratory epithelial cells. The levels of
      chemokines interleukin-8 (IL-8) and released upon activation, normal t cell
      expressed and secreted (RANTES) released by nasal epithelial cell (NEC) cultures
      established from asthmatic and nonasthmatic children were measured by ELISA at 4,
      24, 48, and 72 hr after cells were inoculated with Mp, and were compared with
      baseline release of these factors. The presence of MP on apical membranes of NEC
      after infection was confirmed by transmission electron microscopy, and adherence
      was shown to be inhibited by erythromycin. Mp infection did not alter NEC release
      of IL-8 or RANTES at any time point. In contrast, tumor necrosis factor alpha
      (TNF-alpha) stimulated increased IL-8 at all time points, and respiratory
      syncytial virus (RSV) infection stimulated RANTES release at 48 and 72 hr by NEC.
      These results were not significantly different between NEC from asthmatic and
      nonasthmatic children. As a comparison, peripheral blood mononuclear cells from
      normal human volunteers were also incubated with Mp and had significantly
      increased release of IL-2, IL-6, and TNF-alpha. We conclude that Mp, unlike viral
      pathogens such as RSV, is unlikely to directly stimulate early airway surface
      cytokine responses via mechanisms involving epithelial cells. We speculate that
      the chronic presence of mononuclear cells at the airway surface of asthmatics
      provides a target for Mp-triggered cytokine production.

PMID- 11976404
TI  - Mibefradil improves beta-adrenergic responsiveness and intracellular Ca(2+)
      handling in hypertrophied rat myocardium.
AB  - The present study investigated the effects of mibefradil, a novel T-type channel
      blocker, on ventricular function and intracellular Ca(2+) handling in normal and
      hypertrophied rat myocardium. Ca(2+) transient was measured with the
      bioluminescent protein, aequorin. Mibefradil (2 microM) produced nonsignificant
      changes in isometric contraction and peak systolic intracellular Ca(2+)
      concentration ([Ca(2+)](i)) in normal rat myocardium. Hypertrophied papillary
      muscles isolated from aortic-banded rats 10 weeks after operation demonstrated a
      prolonged duration of isometric contraction, as well as decreased amplitudes of
      developed tension and peak Ca(2+) transient compared with the sham-operated
      group. Additionally, diastolic [Ca(2+)](i) increased in hypertrophied rat
      myocardium. The positive inotropic effect of isoproterenol stimulation was
      blunted in hypertrophied muscles despite a large increase in Ca(2+) transient
      amplitude. Afterglimmers and corresponding aftercontractions were provoked with
      isoproterenol (10(-5) and 10(-4) M) stimulation in 4 out of 16 hypertrophied
      muscles, but were eliminated in the presence of mibefradil (2 microM). In
      addition, hypertrophied muscles in the presence of mibefradil had a significant
      improvement of contractile response to isoproterenol stimulation and a reduced
      diastolic [Ca(2+)](I), although a mild decrease of peak Ca(2+)-transient was also
      shown. However, verapamil (2 microM) did not restore the inotropic and Ca(2+)
      modulating effects of isoproterenol in hypertrophied myocardium. Mibefradil
      partly restores the positive inotropic response to beta-adrenergic stimulation in
      hypertrophied myocardium from aortic-banded rats, an effect that might be useful
      in hypertrophied myocardium with impaired [Ca(2+)](i) homeostasis.

PMID- 11976405
TI  - Sphingoid bases and ceramide induce apoptosis in HT-29 and HCT-116 human colon
      cancer cells.
AB  - Complex dietary sphingolipids such as sphingomyelin and glycosphingolipids have
      been reported to inhibit development of colon cancer. This protective role may be
      the result of turnover to bioactive metabolites including sphingoid bases
      (sphingosine and sphinganine) and ceramide, which inhibit proliferation and
      stimulate apoptosis. The purpose of the present study was to investigate the
      effects of sphingoid bases and ceramides on the growth, death, and cell cycle of
      HT-29 and HCT-116 human colon cancer cells. The importance of the 4,5-trans
      double bond present in both sphingosine and C(2)-ceramide (a short chain analog
      of ceramide) was evaluated by comparing the effects of these lipids with those of
      sphinganine and C(2)-dihydroceramide (a short chain analog of dihydroceramide),
      which lack this structural feature. Sphingosine, sphinganine, and C(2)-ceramide
      inhibited growth and caused death of colon cancer cells in time- and
      concentration-dependent manners, whereas C(2)-dihydroceramide had no effect.
      These findings suggest that the 4,5-trans double bond is necessary for the
      inhibitory effects of C(2)-ceramide, but not for sphingoid bases. Evaluation of
      cellular morphology via fluorescence microscopy and quantitation of fragmented
      low-molecular weight DNA using the diphenylamine assay demonstrated that
      sphingoid bases and C(2)-ceramide cause chromatin and nuclear condensation as
      well as fragmentation of DNA, suggesting these lipids kill colon cancer cells by
      inducing apoptosis. Flow cytometric analyses confirmed that sphingoid bases and
      C(2)-ceramide increased the number of cells in the A(0) peak indicative of
      apoptosis and demonstrated that sphingoid bases arrest the cell cycle at G(2)/M
      phase and cause accumulation in the S phase. These findings establish that
      sphingoid bases and ceramide induce apoptosis in colon cancer cells and implicate
      them as potential mediators of the protective role of more complex dietary
      sphingolipids in colon carcinogenesis.

PMID- 11976406
TI  - Retinoblastoma function is a better indicator of cellular phenotype in cultured
      breast adenocarcinoma cells than retinoblastoma expression.
AB  - Loss of or lowered retinoblastoma (Rb) expression has been included as a
      prognostic indicator in breast cancer. Low or no Rb expression is seen most
      commonly in high-grade breast adenocarcinomas, suggesting that a relationship may
      exist between loss of Rb and a less differentiated state, high proliferation
      rate, and high metastatic potential. In this study, we compared Rb function in
      two established breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231, and in an
      established immortalized mammary epithelial cell line, MCF10A. Cells were
      synchronized in G0/G1 and were released for several durations, at which time
      total Rb protein, mRNA, and Rb/E2F/DNA complex formation were evaluated. Rb
      protein was significantly higher in the tumor cells than in MCF10A cells.
      However, Rb function was high for a longer duration in MCF10A cells as compared
      with MCF-7 and MDA-MB-231 cells. Our data support the general conclusion that Rb
      function, but not necessarily Rb protein, is lower in highly malignant breast
      adenocarcinoma cells as compared with lower grade tumor cells. These results
      emphasize the relevance of assessing Rb function over Rb protein. This is
      particularly important if Rb is to be used as a prognostic indicator for breast
      adenocarcinoma.

PMID- 11976407
TI  - Biodegradable, elastic shape-memory polymers for potential biomedical
      applications.
AB  - The introduction of biodegradable implant materials as well as minimally invasive
      surgical procedures in medicine has substantially improved health care within the
      past few decades. This report describes a group of degradable thermoplastic
      polymers that are able to change their shape after an increase in temperature.
      Their shape-memory capability enables bulky implants to be placed in the body
      through small incisions or to perform complex mechanical deformations
      automatically. A smart degradable suture was created to illustrate the potential
      of these shape-memory thermoplastics in biomedical applications.

PMID- 11976408
TI  - A cyclic model of the universe.
AB  - We propose a cosmological model in which the universe undergoes an endless
      sequence of cosmic epochs that begin with a "bang" and end in a "crunch."
      Temperature and density at the transition remain finite. Instead of having an
      inflationary epoch, each cycle includes a period of slow accelerated expansion
      (as recently observed) followed by contraction that produces the homogeneity,
      flatness, and energy needed to begin the next cycle.

PMID- 11976410
TI  - Electron microscopic characterization of silver nanowire arrays.

PMID- 11976411
TI  - Science, censorship, and public health.

PMID- 11976409
TI  - Lymphatic metastasis in the absence of functional intratumor lymphatics.
AB  - Lymphatic metastasis contributes to mortality from solid tumors. Whether
      metastasizing cancer cells reach lymph nodes via intratumor lymphatic vessels is
      unknown. Here, we examine functional lymphatics associated with mouse tumors
      expressing normal or elevated levels of vascular endothelial growth factor-C
      (VEGF-C), a molecule that stimulates lymphangiogenesis. Although VEGF-C
      overexpression increased lymphatic surface area in the tumor margin and lymphatic
      metastasis, these tumors contained no functional lymphatics, as assessed by four
      independent functional assays and immunohistochemical staining. These findings
      suggest that the functional lymphatics in the tumor margin alone are sufficient
      for lymphatic metastasis and should be targeted therapeutically.

PMID- 11976412
TI  - Climate change. Pachauri defeats Watson in new chapter for global panel.

PMID- 11976413
TI  - High-energy physics. Neutrino census nails chameleon particles.

PMID- 11976414
TI  - Evolutionary biology. Darwin's avian muses continue to evolve.

PMID- 11976415
TI  - Defense science. Jason hooks up with new sponsor.

PMID- 11976416
TI  - Genetics. One gene determines bee social status.

PMID- 11976417
TI  - Paleontology. 'Fantastic' fossil helps narrow data gap.

PMID- 11976418
TI  - Cosmology. Eternal-universe idea comes full circle.

PMID- 11976420
TI  - Museums. In New York City, a building blooms.

PMID- 11976419
TI  - Biodefense. New anthrax vaccine gets a green light.

PMID- 11976421
TI  - Space station. NASA's O'Keefe tangles with Texans.

PMID- 11976422
TI  - Scientific misconduct. Hall probe continues; no 'willful' fraud.

PMID- 11976423
TI  - Infectious disease. Siberia's deadly stalker emerges from the shadows.

PMID- 11976424
TI  - Infectious disease. A many-headed medusa.

PMID- 11976425
TI  - Infectious disease. Another disease blights families in Siberia's far north.

PMID- 11976426
TI  - Paleontology. A fossil treasure trove hidden in Goethe's city.

PMID- 11976427
TI  - Astrobiology science conference. Astrobiologists try to 'follow the water to
      life'.

PMID- 11976428
TI  - French science. Storming the Bastille.

PMID- 11976429
TI  - Nuclear waste. Yucca Mountain.

PMID- 11976430
TI  - Reaction dynamics. Bending or breaking the rules?

PMID- 11976431
TI  - Atmospheric science. The dust settles on water vapor feedback.

PMID- 11976432
TI  - Transcription. Of chips and ChIPs.

PMID- 11976433
TI  - Immunology. Lethal weapons.

PMID- 11976435
TI  - Retrospective. Willibald Jentschke (1911-2002).

PMID- 11976434
TI  - Genomics. A crisis in postgenomic nomenclature.

PMID- 11976436
TI  - The Sun's role in climate variations.
AB  - Is the Sun the controller of climate changes, only the instigator of changes that
      are mostly forced by the system feedbacks, or simply a convenient scapegoat for
      climate variations lacking any other obvious cause? This question is addressed
      for suggested solar forcing mechanisms operating on time scales from billions of
      years to decades. Each mechanism fails to generate the expected climate response
      in important respects, although some relations are found. The magnitude of the
      system feedbacks or variability appears as large or larger than that of the solar
      forcing, making the Sun's true role ambiguous. As the Sun provides an explicit
      external forcing, a better understanding of its cause and effect in climate
      change could help us evaluate the importance of other climate forcings (such as
      past and future greenhouse gas changes).

PMID- 11976437
TI  - Endocannabinoid signaling in the brain.
AB  - The primary psychoactive ingredient in cannabis, Delta9-tetrahydrocannabinol
      (Delta9-THC), affects the brain mainly by activating a specific receptor (CB1).
      CB1 is expressed at high levels in many brain regions, and several endogenous
      brain lipids have been identified as CB1 ligands. In contrast to classical
      neurotransmitters, endogenous cannabinoids can function as retrograde synaptic
      messengers: They are released from postsynaptic neurons and travel backward
      across synapses, activating CB1 on presynaptic axons and suppressing
      neurotransmitter release. Cannabinoids may affect memory, cognition, and pain
      perception by means of this cellular mechanism.

PMID- 11976439
TI  - Unraveling the causes of diabetes.

PMID- 11976440
TI  - Lupus: mysterious disease holds its secrets tight.

PMID- 11976441
TI  - Research funding: new kids on the block.

PMID- 11976443
TI  - Balancing life-style and genomics research for disease prevention.
AB  - Genetic and environmental factors, including diet and life-style, both contribute
      to cardiovascular disease, cancers, and other major causes of mortality, but
      various lines of evidence indicate that environmental factors are most important.
      Overly enthusiastic expectations regarding the benefits of genetic research for
      disease prevention have the potential to distort research priorities and spending
      for health. However, integration of new genetic information into epidemiologic
      studies can help clarify causal relations between both life-style and genetic
      factors and risks of disease. Thus, a balanced approach should provide the best
      data to make informed choices about the most effective means to prevent disease.

PMID- 11976442
TI  - Schizophrenia: diverse approaches to a complex disease.
AB  - Schizophrenia is a debilitating mental illness that affects 1% of the population.
      Despite intensive study, its molecular etiology remains enigmatic. Like many
      common diseases, schizophrenia is multifactorial in origin, with both genetic and
      environmental contributions likely playing an important role in the manifestation
      of symptoms. Recent advances based on pharmacological studies, brain imaging
      analyses, and genetic research are now converging on tantalizing leads that point
      to a central role for several neurotransmitters, including dopamine, glutamate,
      and serotonin, that may interface with neurodevelopmental defects reflecting
      disease-related genetic aberrations. Here, we provide a brief overview of the
      parallel approaches being used to identify the molecular causes of schizophrenia
      and discuss possible directions for future research.

PMID- 11976444
TI  - Complex disease and the new clinical sciences.
AB  - Medical research today is dominated by a genocentric point of view. At the same
      time, clinical discovery and patient-oriented research have become less common.
      Here, I suggest that these developments are interdependent, each representing the
      flip side of an inaccurate view of how clinical advance occurs.

PMID- 11976445
TI  - Maneuvering in the complex path from genotype to phenotype.
AB  - Human disease phenotypes are controlled not only by genes but by lawful self
      organizing networks that display system-wide dynamics. These networks range from
      metabolic pathways to signaling pathways that regulate hormone action. When
      perturbed, networks alter their output of matter and energy which, depending on
      the environmental context, can produce either a pathological or a normal
      phenotype. Study of the dynamics of these networks by approaches such as
      metabolic control analysis may provide new insights into the pathogenesis and
      treatment of complex diseases.

PMID- 11976446
TI  - Nanotubes in a flash--ignition and reconstruction.

PMID- 11976448
TI  - Theoretical study of the validity of the Born-Oppenheimer approximation in the Cl
      + H2 --> HCl + H reaction.
AB  - Reactivity of the excited spin-orbit state of Cl with H2 to yield ground-state
      HCl products is forbidden by the Born-Oppenheimer (BO) approximation. We used new
      ab initio potential energy surfaces and exact quantum scattering calculations to
      explore the extent of electronic nonadiabaticity in this reaction. In direct
      contrast to recent experiments, we predict that the BO-allowed reaction of the
      ground spin-orbit state will be much more efficient than the BO-forbidden
      reaction of the excited spin-orbit state. Also, Coriolis coupling opens up an
      electronically nonadiabatic inelastic channel, which competes substantially with
      reaction.

PMID- 11976449
TI  - Dynamic aggregation of chiral spinners.
AB  - An object spinning at the surface of a liquid creates a chiral vortex. If the
      spinning object is itself chiral, its shape modifies the characteristics of the
      vortex; interactions between that vortex and other vortices then depend on the
      chirality of the objects that produce them. This paper describes the aggregation
      of millimeter-sized, chiral magnetized plates floating at a liquid-air interface
      and rotating under the influence of a rotating external magnetic field. This
      external field confines all the plates at densities that cause the vortices they
      generate to interact strongly. For one set of plates investigated, plates of one
      chirality attract one another, and plates of the other chirality repel other
      plates of both chiralities.

PMID- 11976447
TI  - Unpredictable evolution in a 30-year study of Darwin's finches.
AB  - Evolution can be predicted in the short term from a knowledge of selection and
      inheritance. However, in the long term evolution is unpredictable because
      environments, which determine the directions and magnitudes of selection
      coefficients, fluctuate unpredictably. These two features of evolution, the
      predictable and unpredictable, are demonstrated in a study of two populations of
      Darwin's finches on the Galapagos island of Daphne Major. From 1972 to 2001,
      Geospiza fortis (medium ground finch) and Geospiza scandens (cactus finch)
      changed several times in body size and two beak traits. Natural selection
      occurred frequently in both species and varied from unidirectional to
      oscillating, episodic to gradual. Hybridization occurred repeatedly though
      rarely, resulting in elevated phenotypic variances in G. scandens and a change in
      beak shape. The phenotypic states of both species at the end of the 30-year study
      could not have been predicted at the beginning. Continuous, long-term studies are
      needed to detect and interpret rare but important events and nonuniform
      evolutionary change.

PMID- 11976450
TI  - Thermochemistry and aqueous solubilities of hydrotalcite-like solids.
AB  - Hydrotalcites are used in technology as catalysts and anion exchangers and are
      important sinks for environmental contaminants. Their compositional variability
      makes it important, but difficult, to estimate their aqueous solubility. We
      report calorimetric measurements of the heats of formation of cobalt-aluminum
      hydrotalcite phases. The heat and free energy of formation from the elements are
      equal to those of mechanical mixtures of binary compounds, namely hydroxides and
      carbonates. The interlayer anion is much more important than the cation in
      determining the solubility of the hydrotalcite phase and its ability to contain
      or release heavy metals to the environment. Because hydrotalcites do not have an
      unreactive polymer as a structural core, their aqueous stability will change
      dramatically with composition, particularly with anion content. This simple
      mechanical mixture model allows prediction of aqueous solubilities and trace
      metal retention in a variety of geochemical settings.

PMID- 11976451
TI  - The shaping of continental slopes by internal tides.
AB  - The angles of energy propagation of semidiurnal internal tides may determine the
      average gradient of continental slopes in ocean basins (approximately 2 to 4
      degrees). Intensification of near-bottom water velocities and bottom shear
      stresses caused by reflection of semi-diurnal internal tides affects
      sedimentation patterns and bottom gradients, as indicated by recent studies of
      continental slopes off northern California and New Jersey. Estimates of bottom
      shear velocities caused by semi-diurnal internal tides are high enough to inhibit
      deposition of fine-grained sediment onto the slopes.

PMID- 11976452
TI  - Global cooling after the eruption of Mount Pinatubo: a test of climate feedback
      by water vapor.
AB  - The sensitivity of Earth's climate to an external radiative forcing depends
      critically on the response of water vapor. We use the global cooling and drying
      of the atmosphere that was observed after the eruption of Mount Pinatubo to test
      model predictions of the climate feedback from water vapor. Here, we first
      highlight the success of the model in reproducing the observed drying after the
      volcanic eruption. Then, by comparing model simulations with and without water
      vapor feedback, we demonstrate the importance of the atmospheric drying in
      amplifying the temperature change and show that, without the strong positive
      feedback from water vapor, the model is unable to reproduce the observed cooling.
      These results provide quantitative evidence of the reliability of water vapor
      feedback in current climate models, which is crucial to their use for global
      warming projections.

PMID- 11976453
TI  - The North Atlantic spring phytoplankton bloom and Sverdrup's critical depth
      hypothesis.
AB  - More than 50 years ago, Harald Sverdrup developed a simple model for the
      necessary conditions leading to the spring bloom of phytoplankton. Although this
      model has been used extensively across a variety of aquatic ecosystems, its
      application requires knowledge of community compensation irradiance (IC), the
      light level where photosynthetic and ecosystem community loss processes balance.
      However, reported IC values have varied by an order of magnitude. Here, IC
      estimates are determined using satellite and hydrographic data sets consistent
      with the assumptions in Sverdrup's 1953 critical depth hypothesis. Retrieved
      values of IC are approximately uniform throughout much of the North Atlantic with
      a mean value of 1.3 mol photons meter-2 day-1. These community-based IC
      determinations are roughly twice typical values found for phytoplankton alone
      indicating that phytoplankton account for approximately one-half of community
      ecosystem losses. This work also suggests that important aspects of heterotrophic
      community dynamics can be assessed using satellite observations.

PMID- 11976454
TI  - Role of Yersinia murine toxin in survival of Yersinia pestis in the midgut of the
      flea vector.
AB  - Transmission by flea bite is a relatively recent adaptation that distinguishes
      Yersinia pestis, the plague bacillus, from closely related enteric bacteria.
      Here, a plasmid-encoded phospholipase D (PLD), previously characterized as
      Yersinia murine toxin (Ymt), was shown to be required for survival of Y. pestis
      in the midgut of its principal vector, the rat flea Xenopsylla cheopis.
      Intracellular PLD activity appeared to protect Y. pestis from a cytotoxic
      digestion product of blood plasma in the flea gut. By enabling colonization of
      the flea midgut, acquisition of this PLD may have precipitated the transition of
      Y. pestis to obligate arthropod-borne transmission.

PMID- 11976455
TI  - Trophic control of production in a rocky intertidal community.
AB  - In the low intertidal zone at Tatoosh Island, Washington, United States, minimal
      estimates of primary production can vary from 0 to an average of 86 kilograms of
      wet mass per square meter per year when the grazing assemblage is manipulated.
      Highly productive annual kelps (Laminariales) replace less productive perennial
      species when macroscopic grazers are reduced or absent, resulting in monodominant
      assemblages of Alaria marginata. Experiments were repeated in seven consecutive
      years. Increased species richness makes no significant additional contribution to
      annual production. Rather, a competitively superior species is favored when its
      enemies are reduced, suggesting that terrestrial perspectives on the role of
      biodiversity that are developed without considering consumers may not be general.

PMID- 11976457
TI  - Influence of gene action across different time scales on behavior.
AB  - Genes can affect natural behavioral variation in different ways. Allelic
      variation causes alternative behavioral phenotypes, whereas changes in gene
      expression can influence the initiation of behavior at different ages. We show
      that the age-related transition by honey bees from hive work to foraging is
      associated with an increase in the expression of the foraging (for) gene, which
      encodes a guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (PKG).
      cGMP treatment elevated PKG activity and caused foraging behavior. Previous
      research showed that allelic differences in PKG expression result in two
      Drosophila foraging variants. The same gene can thus exert different types of
      influence on a behavior.

PMID- 11976456
TI  - No major schizophrenia locus detected on chromosome 1q in a large multicenter
      sample.
AB  - Reports of substantial evidence for genetic linkage of schizophrenia to
      chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans
      of this chromosome in a multicenter sample of 779 informative schizophrenia
      pedigrees. No significant evidence was observed for such linkage, nor for
      heterogeneity in allele sharing among the eight individual samples. Separate
      analyses of European-origin families, recessive models of inheritance, and
      families with larger numbers of affected cases also failed to produce significant
      evidence for linkage. If schizophrenia susceptibility genes are present on
      chromosome 1q, their population-wide genetic effects are likely to be small.

PMID- 11976458
TI  - A tomato cysteine protease required for Cf-2-dependent disease resistance and
      suppression of autonecrosis.
AB  - Little is known of how plant disease resistance (R) proteins recognize pathogens
      and activate plant defenses. Rcr3 is specifically required for the function of Cf
      2, a Lycopersicon pimpinellifolium gene bred into cultivated tomato (Lycopersicon
      esculentum) for resistance to Cladosporium fulvum. Rcr3 encodes a secreted papain
      like cysteine endoprotease. Genetic analysis shows Rcr3 is allelic to the L.
      pimpinellifolium Ne gene, which suppresses the Cf-2-dependent autonecrosis
      conditioned by its L. esculentum allele, ne (necrosis). Rcr3 alleles from these
      two species encode proteins that differ by only seven amino acids. Possible roles
      of Rcr3 in Cf-2-dependent defense and autonecrosis are discussed.

PMID- 11976460
TI  - Evolutionary rate in the protein interaction network.
AB  - High-throughput screens have begun to reveal the protein interaction network that
      underpins most cellular functions in the yeast Saccharomyces cerevisiae. How the
      organization of this network affects the evolution of the proteins that compose
      it is a fundamental question in molecular evolution. We show that the
      connectivity of well-conserved proteins in the network is negatively correlated
      with their rate of evolution. Proteins with more interactors evolve more slowly
      not because they are more important to the organism, but because a greater
      proportion of the protein is directly involved in its function. At sites
      important for interaction between proteins, evolutionary changes may occur
      largely by coevolution, in which substitutions in one protein result in selection
      pressure for reciprocal changes in interacting partners. We confirm one predicted
      outcome of this process-namely, that interacting proteins evolve at similar
      rates.

PMID- 11976459
TI  - A role for skin gammadelta T cells in wound repair.
AB  - Gammadelta T cell receptor-bearing dendritic epidermal T cells (DETCs) found in
      murine skin recognize antigen expressed by damaged or stressed keratinocytes.
      Activated DETCs produce keratinocyte growth factors (KGFs) and chemokines,
      raising the possibility that DETCs play a role in tissue repair. We performed
      wound healing studies and found defects in keratinocyte proliferation and tissue
      reepithelialization in the absence of wild-type DETCs. In vitro skin organ
      culture studies demonstrated that adding DETCs or recombinant KGF restored normal
      wound healing in gammadelta DETC-deficient skin. We propose that DETCs recognize
      antigen expressed by injured keratinocytes and produce factors that directly
      affect wound repair.

PMID- 11976461
TI  - National Technical Advisory Group on Immunization: a major step forward for child
      health.

PMID- 11976462
TI  - Diet and nutritional status of rural preschool children in Punjab.
AB  - OBJECTIVE: To assess diet and nutritional profile of rural preschool children of
      Punjab. STUDY DESIGN: Multistage random sampling method was adopted by following
      probability proportion to population size (PPS). SUBJECT: Four hundred households
      (HH) were covered in each district of Punjab for socio-economic and demographic
      information. All the available individuals from these HHs were included for
      anthropometry and clinical examination. Every fourth household was covered for 24
      hour recall method of diet survey (individual dietary intake). RESULTS: At the
      state level, the intake of macro and micronutrient rich foods such as cereals,
      pulses and green leafy vegetables, milk and milk products and fats and oils were
      lower than the RDI among preschool children. Except for protein, calcium and
      thiamine, the mean intake of all the nutrients was lower than the recommended
      level. About a half of the preschool children (50.3%) were undernourished (> 2SD
      weight for age); 60% were stunted (> 2SD height for age) and 12% were wasted (>
      2SD weight for height). The extent of undernutrition and stunting was lower than
      that reported for the country. There was significant variation in the prevalence
      of severe stunting between the districts (p < 0.001), with the highest being
      observed in the Rupnagar (55%) and the lowest in Hoshiarpur and Sangrur (30%
      each). CONCLUSION: Despite, the reported high rates of economic growth and food
      production in the state, a higher proportion of preschool children were consuming
      diets, which are inadequate with respect to energy, fat, iron, riboflavin,
      vitamin A and vitamin C. The prevalence of undernutrition was high as was found
      in other states.

PMID- 11976463
TI  - Impact of daily versus weekly hematinic supplementation on anemia in pregnant
      women.
AB  - OBJECTIVE: To compare the effectivity of weekly versus daily iron therapy in
      reducing maternal anemia and to evaluate the association of maternal hemoglobin
      and fetal growth. DESIGN: Prospective. SETTING: Tertiary care teaching hospital
      in an urban metropolis. METHOD: 40 pregnant women received daily and 40 pregnant
      women received weekly oral therapy (335 mg of ferrous sulphate and 500 g folic
      acid) for a period of 14 weeks. The age of each pregnant woman and their baseline
      anthropometric data (weight, height and body mass index) were estimated.
      Hemoglobin and hematocrit estimations were carried out during follow period at 4
      wks, 8 wks and 14 weeks. Serum ferritin values as a marker of iron status were
      also calculated in both the groups initially, at 14 weeks and at the time of
      delivery. Fetal anthropometric indices of 137 full term neonates delivered to
      mothers included in either of the supplementation groups or admitted to the
      hospital were also studied in relation to maternal hemoglobin concentration.
      RESULTS: Forty subjects each were initially randomized into groups I and II. The
      age of pregnant women along with their baseline anthropometric data were similar
      in both groups. A total of 29 pregnant women in group I and 27 pregnant women in
      group II could be regularly followed up. The increase in hemoglobin and
      hematocrit values were similar in daily and weekly supplemented mothers. An
      intention to treat analysis also showed similar results. The ferritin values were
      similar at the start of supplementation and after 14 wks of weekly or daily iron
      therapy. Birth weight, crown heel length, head circumference of the neonate and
      placental weight increased significantly with rise in maternal hemoglobin levels.
      CONCLUSION: Weekly iron supplementation is an effective mode of treating anemia
      among pregnant women and maternal anemia during pregnancy is adversely associated
      with fetal growth.

PMID- 11976464
TI  - Steroids in perinatology.

PMID- 11976465
TI  - Prevalence of tuberculous infection and the impact of BCG vaccination on
      tuberculin testing among primary schoolchildren in Turkey.

PMID- 11976467
TI  - Epidemiological factors of dengue hemorrhagic fever in Bangladesh.

PMID- 11976466
TI  - Zinc and magnesium nutriture amongst pregnant mothers of urban slum communities
      in Delhi: a pilot study.

PMID- 11976468
TI  - HIV seropositivity in hospitalized children with high clinical likelihood of
      AIDS.

PMID- 11976469
TI  - Hemodialysis in children.

PMID- 11976470
TI  - Rhino-orbital mucormycosis in acute renal failure.

PMID- 11976471
TI  - Massive fetomaternal hemorrhage with persistent pulmonary hypertension in a
      neonate.

PMID- 11976472
TI  - Infective endocarditis in a child due to Abiotrophia defectivus.

PMID- 11976473
TI  - Hydrops fetalis and extralobar lung sequestration.

PMID- 11976474
TI  - Annuloaortic ectasia in two siblings.

PMID- 11976475
TI  - Cherry red spot.

PMID- 11976476
TI  - Aarskog syndrome.

PMID- 11976477
TI  - Effects of tactile-kinesthetic stimulation in preterms.

PMID- 11976479
TI  - Determining geohelminth prevalence in a semiurban conglomerate in Pondicherry
      questionnaire versus stool examination.

PMID- 11976480
TI  - Standardization of Mantoux test.

PMID- 11976481
TI  - Suppurative parotitis in a neonate.

PMID- 11976483
TI  - Concanavalin A in a dimeric crystal form: revisiting structural accuracy and
      molecular flexibility.
AB  - A structure of native concanavalin A (ConA), a hardy perennial of structural
      biology, has been determined in a dimeric crystal form at a resolution of 1.56 A
      (space group C222(1); unit-cell parameters a = 118.70, b = 101.38, c = 111.97 A;
      two molecules in the asymmetric unit). The structure has been refined to an
      R(free) of 0.206 (R = 0.178) after iterative model building and phase-bias
      removal using Shake&wARP. Correspondence between calculated water-tyrosine
      interactions and experimentally observed structures near the saccharide-binding
      site suggests that the observed interactions between Tyr12 and water in various
      crystal forms are to be expected and are not unique to the presence of an active
      site. The present structure differs from previously reported atomic resolution
      structures of ConA in several regions and extends insight into the conformational
      flexibility of this molecule. Furthermore, this third, low-temperature, structure
      of ConA in a different crystal form, independently refined using powerful model
      bias removal techniques, affords the opportunity to revisit assessment of
      accuracy and precision in high- or atomic resolution protein structures. It is
      illustrated that several precise structures of the same molecule can differ
      substantially in local detail and users of crystallographic models are reminded
      to consider the potential impact when interpreting structures. Suggestions on how
      to effectively represent ensembles of crystallographic models of a given molecule
      are provided.

PMID- 11976482
TI  - 3-Carboxy-cis,cis-muconate lactonizing enzyme from Neurospora crassa: MAD phasing
      with 80 selenomethionines.
AB  - The structure of 3-carboxy-cis,cis-muconate lactonizing enzyme from Neurospora
      crassa was determined at 3.0 A resolution. Phase information was derived from a
      multiwavelength anomalous dispersion (MAD) experiment conducted at three
      wavelengths using crystals of fully substituted selenomethionine protein.
      However, the structure determination was not routine owing to the relatively poor
      quality of the diffraction data and the large number of twofolds in the unit
      cell. Eventually, 80 selenium sites were identified by the combined use of direct
      methods and real-space map interpretation. This represents one of the largest
      selenium substructures solved and used for phasing. Some of the difficulties in
      the structure determination and the methods used to address them are discussed.

PMID- 11976484
TI  - The structure of substrate-free microbial ribonuclease binase and of its
      complexes with 3'GMP and sulfate ions.
AB  - The structures of Bacillus intermedius ribonuclease (binase), an extracellular
      109-residue enzyme, and its complexes with 3'GMP and sulfate ions were solved at
      1.65 and 2.0 A, respectively. The structures were refined using REFMAC. The
      crystal of free binase belongs to the space group C2, whereas the crystals of
      complexes belong to the space group P2(1)2(1)2(1). In both crystal lattices the
      asymmetric unit contains two molecules which form an identical dimer. The
      structure of the dimer is such that only one of its subunits can bind the
      nucleotide in the 3'GMP-binase complex, where the guanyl base is located in the
      recognition loop of the enzyme. In both binase complex structures the phosphate
      group of 3'GMP or one of the sulfate ions make an electrostatic interaction with
      the binase molecule at the catalytic site. A second phosphate-binding site was
      found in the structures of the complexes at the cleft formed by the loop 34-39,
      the main chain of Arg82 and the side chain of Trp34. Comparison of the complex
      and unliganded enzyme crystal structures shows that there are some small but
      distinct differences in the specificity loop (56-62) and in the loops 34-39 and
      99-104 associated with the binding of the nucleotide and sulfate ions.

PMID- 11976485
TI  - Thaumatin crystallization aboard the International Space Station using liquid
      liquid diffusion in the Enhanced Gaseous Nitrogen Dewar (EGN).
AB  - This paper reports results from the first biological crystal-growth experiment on
      the International Space Station (ISS). Crystals of thaumatin were grown using
      liquid-liquid diffusion in Tygon tubing transported in the Enhanced Gaseous
      Nitrogen Dewar (EGN). Different volume ratios and concentrations of protein and
      precipitant were used to test different adaptations of the vapor-diffusion
      crystallization recipe to the liquid-liquid diffusion method. The EGN warmed up
      from 77 to 273 K in about 4 d, about the same time it took to warm from 273 to
      293 K. The temperature within the EGN was 293-297 K for the majority of the
      experiment. Air gaps that blocked liquid-liquid diffusion formed in the tubes.
      Nonetheless, crystals were grown. Synchrotron diffraction data collected from the
      best space-grown crystal extended to 1.28 A, comparable to previous studies of
      space-grown thaumatin crystals. The resolution of the best ground-control crystal
      was only 1.47 A. It is not clear if the difference in diffraction limit arises
      from factors other than crystal size. Improvements in temperature control and the
      elimination of air gaps are needed, but the results show that the EGN on the ISS
      can be used to produce space-grown crystals that diffract to high resolution.

PMID- 11976487
TI  - Conformations of amino acids in proteins.
AB  - The main-chain conformations of 237 384 amino acids in 1042 protein subunits from
      the PDB were analyzed with Ramachandran plots. The populated areas of the
      empirical Ramachandran plot differed markedly from the classical plot in all
      regions. All amino acids in alpha-helices are found within a very narrow range of
      phi, psi angles. As many as 40% of all amino acids are found in this most
      populated region, covering only 2% of the Ramachandran plot. The beta-sheet
      region is clearly subdivided into two distinct regions. These do not arise from
      the parallel and antiparallel beta-strands, which have quite similar
      conformations. One beta region is mainly from amino acids in random coil. The
      third and smallest populated area of the Ramachandran plot, often denoted left
      handed alpha-helix, has a different position than that originally suggested by
      Ramachandran. Each of the 20 amino acids has its own very characteristic
      Ramachandran plot. Most of the glycines have conformations that were considered
      to be less favoured. These results may be useful for checking secondary-structure
      assignments in the PDB and for predicting protein folding.

PMID- 11976486
TI  - Simulated-annealing real-space refinement as a tool in model building.
AB  - Methods have been developed that further automate the building of macromolecular
      structures into electron-density maps. The software supports molecular-dynamics
      real-space refinement of an atomic model to local regions of a map within the
      context of a popular molecular-modeling program, O [Jones et al. (1991), Acta
      Cryst. A47, 110-119]. It is implemented as a module to the CNS refinement package
      [Brunger et al. (1998), Acta Cryst. D54, 905-921], controlled by a graphical user
      interface and commands executed directly through the molecular-graphics package.
      The method is illustrated with examples of the building and rebuilding of protein
      and nucleic acid models in which laborious manual adjustments are avoided. The
      resulting models show improved convergence during subsequent reciprocal-space
      refinement. The novel feature of the RSRef2000 software is the combination of
      simulated-annealing optimization with local real-space refinement, allowing
      several local minima to be explored quickly and automatically within the context
      of interactive model building.

PMID- 11976488
TI  - The mechanism of iron uptake by transferrins: the X-ray structures of the 18 kDa
      NII domain fragment of duck ovotransferrin and its nitrilotriacetate complex.
AB  - In a previous paper [Lindley et al. (1993), Acta Cryst. D49, 292-304], the X-ray
      structure analysis of the 18 kDa fragment of duck ovotransferrin, corresponding
      to the NII domain of the intact protein, was reported at a resolution of 2.3 A.
      In this structure, the Fe(III) cation binds to two tyrosine residues and the
      synergistic carbonate anion in an identical manner to that found in the intact
      protein. However, the aspartate and histidine residues, normally involved in iron
      binding in transferrins, are absent in the fragment and it was not possible to
      unequivocally define what had replaced them. The electron density was tentatively
      assigned to be a mixture of peptides, presumably resulting from the proteolytic
      preparation of the fragment, binding to the iron through their amino and
      carboxylate termini. A more recent X-ray analysis of the fragment, from a
      different preparation, has resulted in a structure at 1.95 A, in which glycine
      appears to be the predominant residue bound to the cation. In an alternative
      attempt to clarify the binding of iron to the 18 kDa fragment, the metal was
      removed by dialysis and replaced in the form of ferric nitrilotriacetate.
      Crystallization of this complex has resulted in an X-ray structure at 1.90 A in
      which the Fe(III) is bound to the synergistic carbonate anion and only one
      tyrosine residue in a manner almost identical to the intact protein. The
      carboxylate groups and the tertiary amino group of the nitrilotriacetate occupy
      the remaining coordination sites. The second tyrosine residue, Tyr95, is not
      bound directly to the iron. The implication of these structures with respect to
      the mechanism of iron binding by the transferrins is addressed.

PMID- 11976489
TI  - Detection and characterization of merohedral twinning in two protein crystals:
      bacteriorhodopsin and p67(phox).
AB  - The estimation of the twinning ratio in crystals of two proteins,
      bacteriorhodopsin and a truncated form of p67(phox), is described. Various
      approaches are combined to detect and determine accurately the twinning ratio.
      For each protein, three data sets from crystals exhibiting twinning ratios
      ranging from 0 to almost 50% are analysed. Self-rotation functions and R(sym)
      values considering space groups of higher symmetry are indicative of twinning.
      Precise values of the twinning ratios are derived from Yeates' statistical
      approaches and Britton plots. The twinning ratios are also obtained by analysing
      the second-, third- and fourth-order moments of the intensity distribution. The
      twinning ratios obtained from the various approaches are compared. Second-, third
      and fourth-order moments of the intensity distribution are useful indicators for
      evaluating the twinning precisely in order to correct the intensities or to
      screen rapidly for non-twinned crystals.

PMID- 11976490
TI  - Rearrangement of Cruickshank's formulae for the diffraction-component precision
      index.
AB  - The formulae for the diffraction-component precision index introduced by
      Cruickshank [(1999), Acta Cryst. D55, 583-601] are simplified using two
      approximations. A rearranged formula for the precision index is presented which
      can readily be calculated from experimental data. It is shown that the precision
      varies as (resolution)(5/2) if R and completeness are maintained. It varies as
      (completeness of intensity measurement)(-5/6) and its dependence on the inclusion
      of solvent atoms is discussed.

PMID- 11976491
TI  - Comparison of different crystal forms of 3-dehydroquinase from Salmonella typhi
      and its implication for the enzyme activity.
AB  - The type I 3-dehydroquinate dehydratase (DHQase) which catalyses the reversible
      dehydration of 3-dehydroquinic acid to 3-dehydroshikimic acid is involved in the
      shikimate pathway for the biosynthesis of aromatic compounds. The shikimate
      pathway is absent in mammals, which makes structural information about DHQase
      vital for the rational design of antimicrobial drugs and herbicides. The
      crystallographic structure of the type I DHQase from Salmonella typhi has now
      been determined for the native form at 1.78 A resolution (R = 19.9%; R(free) =
      24.7%). The structure of the modified enzyme to which the product has been
      covalently bound has also been determined but in a different crystal form (2.1 A
      resolution; R = 17.7%; R(free) = 24.5%). An analysis of the three available
      crystal forms has provided information about the physiological dimer interface.
      The enzyme relies upon the closure of a lid-like loop to complete its active
      site. As the lid-loop tends to stay in the closed position, dimerization appears
      to play a role in biasing the arrangement of the loop towards its open position,
      thus facilitating substrate access.

PMID- 11976492
TI  - FIP: a highly automated beamline for multiwavelength anomalous diffraction
      experiments.
AB  - FIP is a French Collaborating Research Group (CRG) beamline at the European
      Synchrotron Radiation Facility (ESRF) dedicated exclusively to crystallography of
      biological macromolecules, with a special emphasis on multiwavelength anomalous
      diffraction data collection in the 0.7-1.81 A wavelength range. The optics,
      consisting of long cylindrical grazing-angle mirrors associated with a cryocooled
      double-crystal monochromator, delivers an optimal beam in the corresponding
      energy range. The high level of automation, which includes automated crystal
      centring, automated data-collection management and data processing, makes the use
      of this beamline very easy. This is illustrated by the large number of
      challenging structures that have been solved since 1999.

PMID- 11976493
TI  - Three-dimensional structure of an immunoglobulin light-chain dimer with
      amyloidogenic properties.
AB  - The X-ray structure of an immunoglobulin light-chain dimer isolated from the
      urine as a "Bence-Jones protein" from a patient with multiple myeloma and
      amyloidosis (Sea) was determined at 1.94 A resolution and refined to R and
      R(free) factors of 0.22 and 0.25, respectively. This "amyloidogenic" protein
      crystallized in the orthorhombic P2(1)2(1)2(1) space group with unit-cell
      parameters a = 48.28, b = 83.32, c = 112.59 A as determined at 100 K. In the
      vital organs (heart and kidneys), the equivalent of the urinary protein produced
      fibrillar amyloid deposits which were fatal to the patient. Compared with the
      amyloidogenic Mcg light-chain dimer, the Sea protein was highly soluble in
      aqueous solutions and only crystallized at concentrations approaching 100 mg ml(
      1). Both the Sea and Mcg proteins packed into crystals in highly ordered
      arrangements typical of strongly diffracting crystals of immunoglobulin
      fragments. Overall similarities and significant differences in the three
      dimensional structures and crystalline properties are discussed for the Sea and
      Mcg Bence-Jones proteins, which together provide a generalized model of
      abnormalities present in lambda chains, facilitating a better understanding of
      amyloidosis of light-chain origin (AL).

PMID- 11976494
TI  - The structure of L-rhamnulose-1-phosphate aldolase (class II) solved by low
      resolution SIR phasing and 20-fold NCS averaging.
AB  - The enzyme L-rhamnulose-1-phosphate aldolase catalyzes the reversible cleavage of
      L-rhamnulose-1-phosphate to dihydroxyacetone phosphate and L-lactaldehyde. It is
      a homotetramer with an M(r) of 30 000 per subunit and crystallized in space group
      P3(2)21. The enzyme shows a low sequence identity of 18% with the structurally
      known L-fuculose-1-phosphate aldolase that splits a stereoisomer in a similar
      reaction. Structure analysis was initiated with a single heavy-atom derivative
      measured to 6 A resolution. The resulting poor electron density, a self-rotation
      function and the working hypothesis that both enzymes are C(4) symmetric with
      envelopes that resemble one another allowed the location of the 20 protomers of
      the asymmetric unit. The crystal-packing unit was a D(4)-symmetric propeller
      consisting of five D(4)-symmetric octamers around an internal crystallographic
      twofold axis. Presumably, the propellers associate laterally in layers, which in
      turn pile up along the 3(2) axis to form the crystal. The non-crystallographic
      symmetry was used to extend the phases to the 2.7 A resolution limit and to
      establish a refined atomic model of the enzyme. The structure showed that the two
      enzymes are indeed homologous and that they possess chemically similar active
      centres.

PMID- 11976495
TI  - Crystallization and preliminary X-ray analysis of the full-size cubic core of pig
      2-oxoglutarate dehydrogenase complex.
AB  - The full-length (untruncated) dihydrolipoamide succinyltransferase from pig heart
      was crystallized by the hanging-drop vapour-diffusion method. X-ray diffraction
      patterns indicate that the crystal belongs to space group I432, with unit-cell
      parameter a = 189.9 A. The crystal structure has been preliminarily solved at 7 A
      resolution by the molecular-replacement method. The unit cell contains two cubic
      cores, in each of which 24 subunits of E2 are associated according to
      crystallographic 432 symmetry. At the corners of each cubic core, the catalytic
      domains of E2s form a trimer through tight interactions around the
      crystallographic threefold axes. In the electron-density maps, many small broad
      peaks are observed in regions expected to contain the remaining N-terminal
      domains (the E1/E3-binding domain and the lipoyl domain), suggesting flexibility
      of these domains relative to the core. The architecture of the cubic core is
      similar to that of the other truncated E2s. In the unit cell, however, the core
      core contact occurs in a different direction from that found for the truncated
      proteins.

PMID- 11976496
TI  - Crystallization and preliminary diffraction studies of the ectodomain of the
      envelope glycoprotein D from herpes simplex virus 1 alone and in complex with the
      ectodomain of the human receptor HveA.
AB  - Gycoprotein D (gD) is a glycoprotein expressed on the surface of several human
      and animal alpha herpes viruses. Binding of gD to cell-surface receptors has been
      shown to be necessary for herpes simplex virus 1 and 2 (HSV-1 and HSV-2) cell
      entry. The gD ectodomain consists of 316 residues and has no sequence homology to
      any other proteins of known structure. Two fragments of the HSV-1 gD ectodomain
      (gD(22-260): residues 22-260 and gD(285): residues 1-285) have been crystallized
      in two crystal forms. The complex between gD(285) and the ectodomain of HveA, a
      gD cellular receptor member of the tumor necrosis factor (TNFR) superfamily, has
      also been crystallized. Moreover, insect-cell-expressed selenomethionine
      substituted gD(285) has been purified and crystallized alone and in complex with
      HveA.

PMID- 11976497
TI  - Purification, N-terminal sequencing, crystallization and preliminary X-ray
      diffraction analysis of atratoxin, a new short-chain alpha-neurotoxin from the
      venom of Naja naja atra.
AB  - Atratoxin, a new alpha-neurotoxin purified to homogeneity by a series of liquid
      chromatographies from the venom of Naja naja atra (mainland Chinese cobra), is a
      small single-polypeptide alkaline protein with a pI of about 9.5 and molecular
      weight of 6952 Da estimated by mass spectrometry. Although the sequencing of the
      N-terminal 15 residues (LECHNQQTTQQPEGG) shows that this neurotoxic protein
      contains most of the residues, especially at the conserved positions, of the
      consensus sequence of short-chain alpha-neurotoxins, the natural mutations in the
      N-terminal Loop-1 presented by the sequence alignment may have structural or
      functional implications for the interactions between alpha-neurotoxins and
      related receptors. Single crystals of atratoxin have been grown from drops
      containing the necessary Cu(2+) ions by the conventional hanging-drop vapour
      diffusion method. The crystals diffract X-rays to 1.6 A resolution and belong to
      space group C222(1), with unit-cell parameters a = 47.36, b = 47.83, c = 91.31 A,
      corresponding to a volume-to-mass ratio of 1.85 A(3) Da(-1) and two molecules in
      each asymmetric unit.

PMID- 11976498
TI  - Characterization and crystallization of a novel haemoglobinase from pathogenic
      Escherichia coli.
AB  - A haemoglobin-degrading enzyme from pathogenic Escherichia coli has been cloned,
      expressed and purified to homogeneity. The pure protein proteolyses haemoglobin
      and binds haem. In vivo, its role is to remove haem from haemoglobin and pass it
      to the bacteria, allowing them to overcome the limiting concentration of iron
      available in the body. The protein has been crystallized using polyethylene
      glycol to give crystals in a hexagonal space group with unit-cell parameters a =
      b = 114.6, c = 434.3 A. X-ray data have been collected to 2.5 A resolution. This
      is the first member of the SPATE (serine protease autotransporters of
      Enterobacteriaceae) family of autotransporter proteins to be crystallized.

PMID- 11976499
TI  - Cloning, high-level expression, purification and crystallization of peptide
      deformylase from Leptospira interrogans.
AB  - A new peptide deformylase (PDF; EC 3.5.1.27) gene from Leptospira interrogans was
      identified and cloned into expression plasmid pET22b(+) and was highly expressed
      in Escherichia coli BL21(DE3). With DEAE-Sepharose anion-exchange chromatography
      followed by Superdex G-75 size-exclusion chromatography, 60 mg of PDF from L.
      interrogans was purified from 1 l of cell culture. Crystallization screening of
      the purified enzyme resulted in two crystal forms, from one of which a 3 A
      resolution X-ray diffraction data set has been collected.

PMID- 11976500
TI  - Crystallization and preliminary X-ray analysis of human carbonic anhydrase III.
AB  - Carbonic anhydrases catalyze the interconversion of carbon dioxide to
      bicarbonate. Human carbonic anhydrase isozyme III with a C-terminal hexahistidine
      tag was overexpressed in Eschericha coli, purified and crystallized. Diffraction
      data (93.4% completeness) were collected to 2.2 A resolution on an in-house R
      AXIS IV++ image-plate system with Osmic mirrors and a Rigaku HU-H3R CU rotating
      anode generator operating at 50 kV and 100 mA. A 60 degrees sweep of data were
      collected from a single crystal with a crystal-to-detector distance of 150 mm and
      a 0.5 degrees oscillation angle per frame using an exposure of 60 s per frame at
      293 K. The crystals were shown to conform to the Laue hexagonal crystal system
      P6, with unit-cell parameters a = 44.7, c = 222.5 A and a scaling R(sym) of 0.087
      for 11 962 unique reflections. Using the known crystal structure of the rat form
      of carbonic anhydrase isozyme III, a molecular-replacement model was built. This
      model was used for rotation and translation searches and uniquely defined the
      space group as P6(5). Rigid-body refinement of the model was used to generate an
      initial phased electron-density map with an R(work) of 31.17%.

PMID- 11976501
TI  - Crystallization and preliminary X-ray analysis of the hydroperoxidase I C
      terminal domain from Escherichia coli.
AB  - Hydroperoxidases (HP) are normally large haem-containing bifunctional enzymes
      capable of acting as both catalases and peroxidases. The C-terminal domain of HPI
      from Escherichia coli (KatG), extending from residue Tyr422 to Leu726, was found
      to be resistant to trypsin proteolysis. The segment of katG encoding this domain
      was cloned and overexpressed to produce a haemless protein that is soluble even
      at concentrations above 30 mg ml(-1). This protein shows a 25% sequence identity
      with cytochrome c peroxidase (CCP) from Saccharomyces cerevisae, despite lacking
      the characteristic catalytic and iron-binding residues. Crystals from this
      protein were grown in 0.6 M sodium citrate buffered to pH 7.5 with HEPES by the
      hanging-drop vapour-diffusion method at 293 K. These crystals diffracted beyond
      2.0 A resolution and belong to space group P2(1)2(1)2(1), with unit-cell
      parameters a = 84.2, b = 98.7, c = 302.8 A. Three pseudo-origin peaks in the
      Patterson maps indicate an unusual packing compatible with the presence of three
      molecules in the crystal asymmetric unit and a solvent content of about 80% by
      volume.

PMID- 11976502
TI  - Crystallization of the functional domain of human thrombopoietin using an antigen
      binding fragment derived from neutralizing monoclonal antibody.
AB  - Thrombopoietin (TPO) is a cytokine which primarily stimulates
      megakaryocytopoiesis and thrombopoiesis. The functional domain of TPO (TPO(163))
      consisting of the N-terminal 163 amino acids was prepared and crystallized. Since
      the crystallization of TPO(163) was unsuccessful using the standard screening
      methods, a Fab fragment derived from a neutralizing monoclonal antibody was used
      for crystallization. It was found that the TPO(163)-Fab complex crystallized
      reproducibly in 0.1 M potassium phosphate buffer pH 6.0 containing 20-25%
      polyethylene glycol 4000. Thin crystals (0.2 x 0.2 x 0.02 mm) grew in two space
      groups: P2(1), with unit-cell parameters a = 133.20, b = 46.71, c = 191.47 A,
      beta = 90.24 degrees, and C2, with unit-cell parameters a = 131.71, b = 46.48, c
      = 184.63 A, beta = 90.42 degrees. The results of a molecular-replacement analysis
      indicate that the Fab molecules interact with each other and provide a suitable
      interface for crystallization.

PMID- 11976503
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of yeast
      regulatory particle non-ATPase subunit 6 (Nas6p).
AB  - The regulatory particle non-ATPase subunit, Nas6p, from Saccharomyces cerevisiae
      has been crystallized by the hanging-drop vapour-diffusion method using PEG 4000
      as precipitant. The crystals belong to the space group P2(1)2(1)2(1), with unit
      cell parameters a = 41.43 (2), b = 61.74 (1), c = 98.09 (2) A, and contain one
      molecule in the asymmetric unit. A complete diffraction data set using
      synchrotron radiation was collected to 2.6 A resolution.

PMID- 11976504
TI  - Crystallization and preliminary X-ray crystallographic analysis of aspartate 1
      decarboxylase from Helicobacter pylori.
AB  - Aspartate 1-decarboxylase (PanD) catalyzes the alpha-decarboxylation of L
      aspartate in the major route of beta-alanine production for pantothenate
      biosynthesis in bacteria. Pantothenate is synthesized in microorganisms, plants
      and fungi but not in animals and thus the enzymes of its biosynthetic pathway are
      potential targets for developing agents against these organisms. PanD from the
      pathogenic bacterium Helicobacter pylori has been overexpressed in Escherichia
      coli and crystallized using sodium formate as a precipitant. Crystals diffracted
      to better than 1.5 A Bragg spacing upon exposure to synchrotron X-rays.
      Diffraction data to 1.55 A have been collected from a crystal grown in the
      presence of the substrate analogue isoasparagine. The crystal belongs to the
      tetragonal space group I422, with unit-cell parameters a = b = 81.83, c = 93.78
      A. The asymmetric unit contains one subunit of PanD, with a corresponding crystal
      volume per protein mass (V(M)) of 2.85 A(3) Da(-1) and a solvent content of
      56.8%.

PMID- 11976505
TI  - Crystallization and preliminary X-ray crystallographic analysis of UDP-N
      acetylglucosamine acyltransferase from Helicobacter pylori.
AB  - Lipid A, a constituent of lipopolysaccharides, is essential for the growth and
      virulence of most Gram-negative bacteria. This makes its biosynthetic enzymes
      potential targets for development of new antibacterial agents. The first step of
      lipid A biosynthesis is catalyzed by the enzyme UDP-N-acetylglucosamine
      acyltransferase (LpxA). LpxA from the pathogenic bacterium Helicobacter pylori
      has been overexpressed in Escherichia coli and crystallized at 297 K using
      ammonium sulfate and sodium/potassium tartrate as precipitants in the presence of
      a detergent. Diffraction data to 2.1 A resolution have been collected from a
      native crystal. The crystal belongs to space group P6(3)22, with unit-cell
      parameters a = b = 90.69, c = 148.20 A. The asymmetric unit contains one subunit
      of LpxA, with a crystal volume per protein mass (V(M)) of 2.87 A(3) Da(-1) and a
      solvent content of 57.1%.

PMID- 11976506
TI  - Towards the crystal structure of glycerol dehydrogenase from Thermotoga maritima.
AB  - The NAD(+)-dependent glycerol dehydrogenase (EC 1.1.1.6) from the extremely
      thermophilic bacterium Thermotoga maritima has been crystallized in the presence
      of glycerol by the hanging-drop vapour-diffusion method using 2-methyl-2,4
      pentanediol (MPD) as the precipitating agent. Crystals of the enzyme complexed
      with NAD(+) have also been obtained. The crystals belong to the tetragonal system
      with space group I422 and unit-cell parameters a = 105.3, c = 134.5 A. They
      diffract to a maximum resolution of 1.4 A using synchrotron radiation (lambda =
      0.838 A). Crystals of the enzyme-NAD(+) complex diffract to 2.5 A resolution
      using in-house Cu Kalpha radiation.

PMID- 11976507
TI  - Crystallization and preliminary X-ray analysis of recombinant histone HPhA from
      the hyperthermophilic archaeon Pyrococcus horikoshii OT3.
AB  - Recombinant archaeal histone from the hyperthermophile Pyrococcus horikoshii OT3
      (HPhA) was crystallized by the hanging-drop vapour-diffusion method. Crystals
      grew at 291 K in 200 mM (NH(4))(2)SO(4), 100 mM sodium acetate buffer pH 4.6, 19%
      PEG 4000. Diffraction data were obtained to a resolution of 2.3 A from a single
      frozen crystal, which belonged to space group P2(1) with unit-cell parameters a =
      34.99, b = 46.89, c = 35.02 A, alpha = gamma = 90, beta = 104 degrees. The
      asymmetric unit contained two molecules and had a solvent content of
      approximately 35%.

PMID- 11976508
TI  - Metal-ligand geometry relevant to proteins and in proteins: sodium and potassium.
AB  - In previous papers [Harding (2001), Acta Cryst. D57, 401-411, and references
      therein] the geometry of metal-ligand interactions was examined for six metals
      (Ca, Mg, Mn, Fe, Cu, Zn) using the Protein Data Bank and compared with
      information from accurately determined structures of relevant small-molecule
      crystals in the Cambridge Structural Database. Here, the environments of Na(+)
      and K(+) ions found in protein crystal structures are examined in an equivalent
      way. Target M(+).O distances are proposed and the agreement with observed
      distances is summarized. The commonest interactions are with water molecules and
      the next commonest with main-chain carbonyl O atoms.

PMID- 11976512
TI  - Is it time to go back to school?: further education can open the door to an array
      of opportunities.

PMID- 11976509
TI  - Spoilt for choice: protein target selection in a time of plenty.
AB  - Experiences in the application of Boolean logic to the clusters of orthologous
      groups of proteins (COGs) database for target selection in the Mycobacterium
      tuberculosis genome are described.

PMID- 11976513
TI  - Life at the crossroads: where do you go from here?

PMID- 11976514
TI  - Future employment trends in nursing: the nursing shortage has struck just about
      everywhere in the United States and there's no relief in sight--but its effects
      vary by region and specialty.

PMID- 11976515
TI  - Nurses make all the difference: let's accept the challenges of the nursing
      shortage.

PMID- 11976517
TI  - The war on assisted suicide.

PMID- 11976519
TI  - Pain management.

PMID- 11976520
TI  - Clarifying MDI use.

PMID- 11976521
TI  - Medicaid reimbursement for APRNs.

PMID- 11976525
TI  - Helping children cope with public disasters.

PMID- 11976526
TI  - Communicating with children and adolescents.

PMID- 11976527
TI  - Techniques for stabilizing urinary catheters. Tape may be the oldest method, but
      it's not the only one.

PMID- 11976528
TI  - Descending into delirium.

PMID- 11976529
TI  - Tracheostomy emergencies.

PMID- 11976531
TI  - Aspirin for the primary prevention of cardiovascular events: recommendations and
      rationale.

PMID- 11976532
TI  - Opioid-induced constipation. Management is necessary but prevention is better.

PMID- 11976534
TI  - The global reach of the nursing shortage.

PMID- 11976533
TI  - Is it voter assistance or voter solicitation?

PMID- 11976535
TI  - Making it safer down on the farm. Interview by Thomas Schwarz.

PMID- 11976536
TI  - Antibiotic-resistant bacteria on the rise.

PMID- 11976537
TI  - [Cutaneous hydration].

PMID- 11976538
TI  - [The stratum corneum].
AB  - Epidermal differentiation is a continuous process, constituting and renewing a
      protective layer at the skin surface: the stratum corneum, composed of cornified
      keratinocytes that is a barrier to water diffusion. Massive loss of physiologic
      liquids is one of the severest consequences of extensive burns. The stratum
      corneum also protects the subjacent tissues from xenobiotic aggression,
      ultraviolet radiation (70 p. cent of UVB absorption) and from mechanic
      aggression. The integrity of the stratum corneum depends on three elements: 1)
      the physico-chemical quality of the cornified cells, 2) the persistence of
      mechanical junctions uniting these cells and 3) the organization and composition
      of the lipid "mortar" in the intercellular spaces. Since all these components are
      issued from the keratinocyte differentiation process, any perturbation may, in
      time, induce modifications in the "barrier" function of the epidermis. The
      barrier quality varies, depending on its localization (soles of the feet, palms
      of the hands and transitional epidermis of the lips), during skin healing
      (priority to keratinocyte proliferation to the detriment of maturation) under the
      influence of treatment (retinoids, vitamin D derivatives), in the course of aging
      and diseases: ichtyosis and other keratinization genodermatoses, benign
      (including psoriasis) and malignant hyperproliferative diseases. Furthermore, the
      relative impermeability of the stratum corneum is an important factor limiting
      the penetration and diffusion of allergens, but also local drugs delivered with
      local and systemic trans-epidermal treatments. Further knowledge is required on
      the function of the epidermal barrier and the mechanism regulating
      cohesion/desquamation of the stratum corneum to understand certain hereditary
      diseases, improve efficacy of topical therapeutic products and optimize cosmetic
      formulations.

PMID- 11976539
TI  - [Biophysical measurement of cutaneous hydration in vivo].
AB  - The skin, because of its involvement in health, comfort and aesthetics, is a
      particular "organ". Cutaneous hydration is essential for the dermatologist and
      the cosmetician. For the dermatologist, "dry skin" is a clinical sign of an often
      unclear pathogenetic disorder and for the cosmetician it is a discomfort related
      to aging, climatic effects or sun exposure and should be compensated or
      prevented. The essential measurement and objective quantification of cutaneous
      hydration has led to the development of various techniques, based on differing
      biophysical principles and studies aimed at providing better understanding of the
      mechanisms involved. Faced with an abundance of information and means, the aim of
      this review is to briefly present the various techniques and instrumental
      measurements of hydration in vivo, their biophysical principles and their
      pertinence for the clinician.

PMID- 11976540
TI  - [NMF and cosmetology of cutaneous hydration].
AB  - In the stratum corneum, the water binds to the intracellular hygroscopic and
      hydrosoluble substances called "natural moisturizing factors" or NMF. These
      "natural moisturizing factors" contained in the corneocytes are formed during
      epidermal differentiation and may represent up to 10 p. cent of the corneocyte
      mass. They are principally amino acids, carboxylic pyrrolidone acid, lactic acid,
      urea, glucose and mineral ions. Keratinization plays an important part in the
      formation of NMF that exhibit strong osmotic potential attracting the water
      molecules. The binding of water to NMF is the static aspect of cutaneous
      hydration. The second, dynamic, aspect is related to the selective permeability
      of the stratum corneum and to its lipid barrier properties, the permeability of
      which depends on the integrity and nature of the inter-corneocyte lipids and
      their lamellar organization between the cells. In these conditions, hydration
      cosmetics rely on two concepts that can be isolated or associated: the supply of
      hydrophilic substances to the stratum corneum, capable of attracting and
      retaining water (moisturizer) or capable of restoring the barrier in order to
      restore normal water loss or of protecting it against aggression (occlusive).

PMID- 11976541
TI  - [Xerosis].
AB  - The clinical characteristic of xerosis is rough or coarse skin.
      Physiopathologically, the structure of the stratum corneum is modified and
      abnormalities in keratinization, proliferation, surface lipid, water metabolism
      and also pH and sebum exist. There are two forms of xerosis: dry skin forms and
      ichtyosis or ichtyosis-like forms. Xerosis has many etiologies including external
      aggression, senescence, drugs, infection, atopy, deficiencies, malignant
      diseases, endocrine affections, eating disorders and renal failure in dialyzed
      patients. It provokes cutaneous discomfort and unaesthetic appearance that
      justify appropriate treatment. Treatment is essentially local, symptomatic and
      must be accompanied by general measures. Many products include moisturizers and
      emollients (keratolytics: salicylic acid, urea and alpha-hydroxy acid).

PMID- 11976542
TI  - [Cutaneous hydration of the premature and new born].
AB  - The barrier function of the stratum corneum is a fundamental element in
      maintaining cutaneous hydration. Alteration in the stratum corneum leads to the
      loss of this barrier function, with increased transdermal water loss, decreased
      water content and installation of xerosis. Moisturizers correct cutaneous xerosis
      by restoring the stratum corneum. In the new born, the architectural and
      biochemical structure of the stratum corneum is identical to that of infants and
      adults. However, 60 p. cent of new born exhibit physiologic desquamation,
      demonstrating a transitory functional deficit in the stratum corneum, justifying
      emollient treatment. After this physiological desquamation period, emollients are
      reserved for atopic infants or those presenting keratinization disorders. In the
      premature, the epidermis and particularly the stratum corneum are immature; trans
      epidermal water loss is elevated and the skin is dry or even fissural. The
      interest of applying emollients to the skin of premature new born was recently
      demonstrated. Emollients improved the aspect of the skin and also decreased the
      number of infectious episodes.

PMID- 11976543
TI  - [Cutaneous hydration and atopia].
AB  - Altered barrier function of atopic skin is characterized by xerosis, which
      predominantly affects non-inflammatory areas. Xerosis is accompanied by
      morphological, physical and biochemical modifications. The composition of
      epidermal lipids in atopic patients is modified both qualitatively and
      quantitatively. The impact of xerosis and abnormal barrier function in such
      patients is on different levels: --via excessive permeability to allergens and
      atopens, --but also via constant staphylococcal colonization of the atopic skin.
      The role of moisturizing treatments in restoring the barrier function in such
      patients is an important therapeutic aim. Clinical assessment of the effect of
      moisturizing topicals relies on objective means (SCORAD index) but also on
      avoiding corticosteroids or the impact of these moisturizers on patients'quality
      of life.

PMID- 11976544
TI  - [Dry skin and black skin: what are the facts?].
AB  - We present a review of the data in the literature on the potential specificities
      of the stratum corneum of so-called "black" skin, together with the afferent
      cutaneous hydration regulation process. The methodology of the studies is often
      debatable, not only for basic (absence of definition of "black skin") but also
      for technical reasons. Their results are often contradicting. Other than certain
      subtle differences, related to potentially enhanced preservation of the epidermis
      of dark skin from heliodermal xerosis, we conclude in the similarity of the
      physicochemical characteristics of the stratum corneum in the different color of
      skin. Moreover, the data available do not suggest a predisposition of certain
      skin colors to the occurrence of pathological states involving the stratum
      corneum. However, dark skin is characterized by its semiologic capacity of taking
      on a "ashy" aspect related to a better assessment of normal or xerotic stratum
      corneum because of melanic pigmentation.

PMID- 11976545
TI  - [Experimental models of Parkinson's disease].
AB  - Parkinson's disease is a neurodegenerative condition who is related to a large
      loss of nigral dopaminergic neurons leading to a depletion of dopamine in the
      striatum. Experimental research is required in order to increase our knowledge on
      the cellular mechanism and functional consequences of this degenerative process.
      These models allow investigations of new therapeutics in order to improve the
      treatment of patients or to test new drugs able to protect any remaining
      dopaminergic neurons. It is relatively easy to obtain animal models of this
      disease since the target structure and the neuronal population are clearly
      defined. Two neurotoxic compounds are available for inducing animal models of
      Parkinson's disease, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). A new one, rotenone, requires further investigations.
      Each of the neurotoxic compounds requires a specific protocol which can be used
      either with rodents or non-human primates. Progressive lesioning, using MPTP on
      green african monkeys (Cercopithecus aethiops sabaeus) provides the most reliable
      model of the idiopathic disease.

PMID- 11976546
TI  - [Plant biotechnology: an avant-garde research for an ancestral tree, the Ginkgo
      biloba].
AB  - A biotechnology program on Ginkgo biloba was implemented in early 80's, in order
      to improve the biosynthesis in the whole plant and in cell cultures of
      therapeutically active substances, mainly terpenes like ginkgolides. This program
      led to very interesting results in various directions In addition, by the mean of
      in vitro culture, metabolic studies have given some pertinent fundamental results
      adding to the basic understanding of Ginkgo biloba: ginkgolides and bilobalide
      are biosynthesized in the roots of the plant and then translocated to the leaves.
      Two separate and independent metabolic pathways have been underlined for the
      formation of isopentenylpyrophosphate (IPP), the fundamental unit involved both
      in the biosynthesis of the sitosterol and the ginkgolides. The possibilities
      offered by plant biotechnology allowed the implementation of new tools for
      propagation and improvement of the Ginkgo biloba and have enriched the knowledge
      of the biosynthesis of active principles.

PMID- 11976547
TI  - [Biosensors in the pharmaceutical domain].
AB  - Biosensors are analytical devices which incorporate a biological component
      (enzyme, antibody, animal or plant cell, DNA fragments, lipids.) intimately
      connected to a physical transducer (electrode, optical fibre, vibrating quartz.).
      This dual configuration allows the study of a great variety of compounds of
      pharmaceutical interest which react with the biocomponent. The latter is selected
      depending on the application and the performance criteria requested. Biosensors
      are suitable for real time monitoring such as in bioreactors, and for the
      determination of various physiological and pharmacological parameters. Biosensors
      may be employed in home testing (glucose, lactate.), in hospitals (bedside
      testing, emergency, surgery, dialysis monitoring, etc.) in clinical laboratory
      analyses (immunoassays, DNA analysis.) and at research centres. Ideally, a
      biosensor should be easy to use, allowing direct analysis without sample pre
      treatment. Measurements should be automatized and remote controlled. The
      biosensor may be miniaturized for single use or for implementation in sensor
      arrays. Applications to microenvironments (in vivo, single cell.) or discrete one
      shot decentralized tests may also considered.

PMID- 11976548
TI  - [Inactivation of bacterial spores by high hydrostatic pressure].
AB  - High pressure biotechnology was developed in Japan in the 90's. This new
      technology has been used in several domains, including chemical synthesis, food
      industry, physical chemistry of proteins. Moreover, it could be used instead of
      heat or chemical treatment for inactivation of pathogenic micro-organisms.
      Hydrostatic pressures ranging from 100 to 300 MPa cause the inactivation of
      viruses, parasites, yeast and bacteria. However, bacterial spores are
      particularly resistant and their inactivation by high hydrostatic pressure can be
      achieved in combination with synergistic treatments (heat, chemicals and
      ultrasound).

PMID- 11976549
TI  - [Oral tolerance induced by poly (lactide-co-glycolide) containing B
      lactoglobulin].
AB  - Allergies to milk proteins are frequently encountered in the new born population.
      In order to prevent this allergy by inducing oral tolerance, one of the major
      allergenic milk protein, B lactoglobulin (BLG) was entrapped into biodegradable
      Poly (lactide-co-glycolide) microspheres and was then orally given to mice.
      Microspheres are able to protect proteins against degradation by intestinal
      proteolytic enzymes and to target the Peyers patches which are one important
      priming site of the mucosal immune system. Microspheres were prepared by the
      multiple emulsion solvent evaporation method. The goal of the formulation study
      was to associate large amounts of proteins to the smallest amount of polymer so
      that a minimal quantity of microspheres would be administered. It was shown that
      introducing tween 20 in the formulation was able to increase the encapsulation
      efficiency and to better control protein release reducing the burst release
      effect. Moreover, Oral administration of microspheres containing BLG reduced
      significantly (by 10.000) the amount of protein necessary to decrease both
      specific anti BLG IgE and DTH response. In conclusion, microspheres appear to be
      optimal systems to induce oral tolerance.

PMID- 11976550
TI  - [Fractal art in separative sciences].
AB  - Fractal geometry has provided a mathematical formalism for describing complex and
      dynamical structures. It has been applied successfully in a variety of areas such
      as astronomy, economics and biology. Because of its success in such a variety of
      areas it is natural to develop fractal application in separative sciences.

PMID- 11976551
TI  - [Gene therapy: achievements and perspectives].

PMID- 11976552
TI  - [Nosocomial infectious: the realities of an endless fight].
AB  - Nosocomial infections (N.I.), contracted while patients are being cured, are the
      direct price of lightning progress in medicine in the course of the last fifty
      years. Absolute paradox of the end of century, the very place, where the most
      famous surgical and medical events are achieved, is also the same scene where a
      patient may contract infections that sometimes lead to a fatal outcome. With
      10000 deaths per year and millions of additional hospitalization days, NI have
      become a real Public Health problem. They reach especially patients but also the
      staff, and they can be found everywhere a treatment is given (hospital, clinic,
      patient's home). Paradoxically, the first great myth of anti-NI struggle is the
      discovery of antibiotics, one of the hugest advancements for humanity. An
      excessive antibiotherapy prescription, added to a laxism in basic hygiene actions
      (individual or collective) increased for the last thirty years this phenomenon,
      which has now become so extensive that international and national authorities are
      managing this problem. The fight versus NI is an endless struggle because
      treatments will always exist. The rising emergence of antibiotics bacterial
      multiresistance has promoted this whole subject called Hospital Hygiene, a
      discipline which, little by little, regains a dominating place in our Health
      establishments. Bacteria are liable for 85% of NI, while virus and fungi are
      responsible for 15%. Omnipresent on a milliards scale, ubiquitous, the bacterial
      species will be thwarted only if the staff, who is taking care of patients, shows
      a constant vigilance. Immunosuppressive pathologies, age and nutritional
      conditions of the patient, new invasive diagnosis or assistance methods,
      antibiotics selection pressure, and at least a mismanagement of individual
      Hygiene and/or of the premises, are the main conditions leading to the outbreak
      of NI. The NI occurs basically within an early period of ten days after the
      patient's care. Catheter urinary infections, broncho-pneumonic infections with
      ventilation assistance, post-operative wounds and catheter bacteremia are the
      main nosocomial pathologies found in France, and in other european countries or
      in the United States. Staphylococci, Enterococci, Enterobacteria and Pseudomonas
      are the leaders of responsible bacteria but any kind of bacterium, can generate a
      NI, due to associated risk factors. Committees against nosocomial infections
      (Clin) have been organized in France in every public health establishment in
      1988, then in every private health establishment in 1999. Since 1992 inter-aeras
      coordination committees and one national technical committee were instituted. In
      that way was the struggle officially set up. At last the Health National Agency
      of Accredidation and Valuation (ANAES), within the scope of an improvement policy
      concerning the security of and the quality of treatments in every health
      establishment, accepted about ten "standards" or "criterions" recommending
      supervision, education, written proceedings, informations diffusion modes,
      indicators definition in hospital hygiene. 85% of NI are in relation with direct
      or indirect hand transmission: that is the main point. So the first measure
      versus NI is just a fact: "HANDWASHING". It is the most effective method, the
      least expensive but unfortunately the least steady process. Beyond the struggle
      versus NI, all iatrogenic risks must be fought with a coherent control strategy.
      This "multivigilance" is a hard job for every health professional because it must
      be a daily, steady, rigorous and multidisciplinary task. The "Clin" is the
      privileged place for abilities round-up with an effective and permanent
      contribution between clinical structures, microbiology labs, pharmacy,
      administrative and technical sections. Every people belonging to a care unit must
      be equally involved in the rising of NI which activated a real mobilization of
      politicians and professionals who have become sensitive, on a socio-economic and
      an ethical basis. It is a collective and individual problem. Furthermore, the
      strict use of basic rules in hospital hygiene appears to be the KEYSTONE of the
      struggle.

PMID- 11976553
TI  - [Anticonvulsant and forced swim anti-immobility effects of tetrahydro-N, N
      dimethyl-2,2-diphenyl-3-furanemethanamine (AE37): common action mechanism?].
AB  - Tetrahydro-N, N-dimethyl-2, 2-diphenyl-3-furanemethanamine (AE 37) is a newly
      synthesized anticonvulsant drug efficient against electrogenic (maximal
      electroshock: MES) or pentetrazole (PTZ) induced tonic convulsions of mice. It
      also antagonizes the immobility of adult or aged mice in the forced swim test
      (FST), which is used to detect antidepressive properties. Neurochemical changes
      induced by AE37 (antagonistic action on the sodium channel currents and on the
      receptors sensitive to N-methyl-D-aspartic acid) could generate the
      aforementioned pharmacological properties, whereas the partial agonistic action
      of AE 37 on the brain muscarinic receptors seems to confer to this drug
      characteristics of third generation antiepileptic.

PMID- 11976554
TI  - [Synthesis and crystalline structure of cis-monochloro(dimenthylsulfoxide)].
AB  - The synthesis of cis-monochloro(dimethylsulfoxide)(metforminuro) platine(II) was
      investigated. It crystallizes in the monoclinic system, space group P 2(1)/c with
      Z=4. The cell parameters are: a=9.173(2); b=11.286( 2); c=12.556( 3) (A);
      b=99.69(2) degrees. The structure of this compound was refined to R=0.031 and
      wR=0.038 using 1461 independent reflexions with I>3 s(I). The platinum
      coordination is square planar, built up from one Cl, one O from the
      dimethylsulfoxide, and one bidentate chelating ligand (metforminure anion) via
      the two imine nitrogen atoms in cis position. The negative charge of the
      metforminure ligand ensures the electric neutrality in the complex. The crystal
      packing is characterized by four hydrogen bonds, one of which is bifurcated
      (involving Cl atom (intramolecular bonding) and O(i) (intermolecular bonding;
      symmetry code i: x, 3/2-y; 1/2+z).

PMID- 11976555
TI  - [Crystallochemistry of copper (II) and zinc (II) chelates by nonsteroidal
      antiinflammatory drugs].
AB  - Copper(II) and zinc(II) chelates by some non-steroidal antiinflammatory drugs
      NSAIDs (niflumic acid, indomethacin) and 3,5-diisopropylsalicylic acid (DIPS)
      were characterized by single X-ray diffraction methods. Copper(II) complexes by
      these two types of chelates are binuclear compounds, with Cu(2)(DIPS)(4)L(2) or
      Cu(2)(AINS)(4)L(2) formula (L=axial non-NSAID ligand such as diethylether,
      dimethylsulfoxide DMSO). In zinc(II) complex by DIPS, the metal ion is
      tetrahedrally coordinated and the corresponding compound is mononuclear with
      Zn(DIPS)(2)(DMSO)(2) formula. These copper(II) and zinc(II) complexes were found
      to be more active than their parent drugs from the antiinflammatory and
      anticonvulsant properties. It was pointed out that the Cu(2)(DIPS)(4)L(2)
      complexes (L=diethylether, N,N-dimethylformamide) exhibited no rotorod toxicity
      when examined for anticonvulsant activity using the seizure produced by maximal
      electroshock, following oral administration to rats.

PMID- 11976556
TI  - [Dry eyes syndrome: reality and perspectives of treatment].
AB  - Scientific progress over the last decade has provided a better understanding of
      the ocular surface and of dry eye syndromes. The frequency of these conditions is
      high since 10% of all adults and 18% of all elderly persons are concerned. More
      adapted treatment has become available through drug research and development
      (artificial tears without preservatives, carbomeric fluid gels) providing
      substantial patient improvement both in terms of symptoms and comfort of use. The
      next decade will undoubtedly bring forward new agents active on one or more of
      the functional units, the lacrimal film, the ocular surface, eyelids, and the
      principal lacrimal gland.

PMID- 11976557
TI  - Experimental toxicity of Peganum harmala seeds.
AB  - Peganum harmala is plant known since the first century A.D. and still, currently
      used for therapeutic purposes. Harmaline, the active principle of the plant
      seeds, and its derivatives, cause visual troubles, loss of coordination,
      agitation and delirium, and, at high doses, it can produce paralysis. The present
      study was initiated to evaluate the use and manipulation of therapeutic doses of
      aqueous extract of P. harmala. Wistar rats were orally dosed acutely and the
      LD(50) obtained was 2.70+/-0.05g/kg. In chronic studies aqueous extract of P.
      harmala administered orally for six times a week at doses of 1, 1.35 and 2g/kg
      during 3 month period increased transaminases. Changes in glucose and creatinine
      were not significant. No significant gross changes were found at necropsy.
      Histologic study showed liver degeneration and spongiform changes in the central
      nervous system (CNS) in rats treated with 2g/kg dose but not at the therapeutic
      dose of 1g/kg.

PMID- 11976558
TI  - [Research activities of interns in pharmacy].
AB  - During their hospital internship, French pharmacists have many opportunities to
      participate in research activities, especially in post-doctoral work (DEA). We
      conducted a national survey among pharmacy residents and interns to ascertain
      their motivations before completing their diploma. Many (about 50%) considered
      their post-doctorate work as an initiation before starting their scientific
      profession. Other motivations were also noted. This study provides data for
      future comparisons.

PMID- 11976559
TI  - [Pedology in pharmacy: stake, development, difficulties, constraints].
AB  - Pedology is a traditional activity of the pharmacist. To render this service to
      patients, the pharmacist must acquire a certain degree of professional
      proficiency to satisfy patients and comply with the quality regulations of the
      health authorities. Competition with other health care professionals must also be
      considered. To conserve this proficiency, a minimum number of soles would have to
      be sold each week. This requires time and training and thus raises the question
      of subsidiary activities of the pharmacy and its relative importance in the
      pharmacist's activity. The pharmacist who provides pedology services will be
      distinguished by the public, but the risk is the detriment to drug dispensing. A
      critical balance must be reached.

PMID- 11976560
TI  - Molecular mechanisms of insulin-stimulated glucose uptake in adipocytes.
AB  - The stimulation of muscle and adipose tissue glucose metabolism, which is
      ultimately responsible for bringing about post-absorptive blood glucose
      clearance, is the primary clinically relevant action of insulin. Insulin acts on
      many steps of glucose metabolism, but one of the most important effects is its
      ability to increase the rate of cellular glucose transport. This results from the
      translocation of the insulin-responsive transporter isoform, GLUT4, from intra
      cellular vesicular storage sites to the plasma membrane. In adipocytes, a
      substantial amount of cellular GLUT4 is located in a specific highly insulin
      responsive storage pool, termed GLUT4 Storage Vesicles (GSVs). GLUT4 can also
      translocate to the plasma membrane from the recycling endosomal pool which also
      additionally contains the GLUT1 isoform of glucose transporter and the
      transferrin receptor. In this article we review the molecular mechanism by which
      insulin stimulates GLUT4 translocation in adipose cells, including the nature of
      the signaling pathways involved and the role of the cytoskeleton.

PMID- 11976561
TI  - In vivo kinetics of 123 iodine-labelled insulin in skeletal muscle of patients
      with type 2 diabetes. Effect of metformin.
AB  - BACKGROUND: The capillary filtration of albumin (CFA) is often increased in
      diabetic patients. However, the transcapillary transfer of insulin is considered
      to be a key stage in insulin action. The aim was to study the in vivo kinetics of
      123I-labelled human insulin in the skeletal muscle of type 2 diabetic patients
      with an increase in CFA and to evaluate the effect of metformin, using a
      noninvasive method. METHODS: Ten type 2 diabetic patients and 6 healthy control
      subjects were investigated. After an i.v injection of 123I-labelled insulin,
      venous samples were drawn during 75 minutes and radioactivity was counted
      externally by a gammacamera on the contralateral forearm before, during and after
      venous compression. The changes in the serum percentages of bound and free 123I
      were followed during the entire test and the forearm iodine bound to insulin was
      estimated by multiplying the forearm counted radioactivity by the serum
      percentage of bound iodine at the same time. RESULTS: In the diabetic patients
      the maximal increase in the forearm iodine bound to insulin during venous
      compression was lower (p=0.06), and 10 minutes after removal of venous
      compression the forearm retention of labelled insulin was significantly lower
      (p<0.0005) than in controls. After one month of metformin treatment, retention of
      labelled insulin significantly increased (p<0.001) but was still significantly
      lower than in the controls (p<0.001). CONCLUSION: The in vivo kinetics of (123) I
      labelled insulin procedure allows the study of skeletal muscle metabolism
      provided venous compression is exerted. In type 2 diabetic patients a reduction
      of insulin transfer from capillary to tissue despite an increase in CFA, and a
      reduction of the time spent by insulin in the tissues contribute to insulin
      resistance. The latter disorder may be improved by metformin.

PMID- 11976562
TI  - Effects of young barley leaf extract and antioxidative vitamins on LDL oxidation
      and free radical scavenging activities in type 2 diabetes.
AB  - BACKGROUND: The effects of supplementation of young barley leaf extract (BL)
      and/or antioxidative vitamins C and E on different low-density lipoprotein (LDL)
      subfractions susceptibility to oxidation and free radical scavenging activities
      in patients with type 2 diabetes were evaluated. METHODS: Thirty-six type 2
      diabetic patients were enrolled in this study. The subjects received one of the
      following supplements daily for 4 weeks: 15 g BL, 200 mg vitamin C and 200 mg
      vitamin E (CE), or BL plus CE (BL + CE). RESULTS: The lucigenin-chemiluminescence
      (CL) and luminol-CL levels in blood were significantly reduced in all groups.
      Vitamin E content of LDL subfractions increased significantly following
      supplements, especially for BL + CE group. The percent increase of lag times in
      the BL + CE was significantly higher than those in the BL or CE group. The
      antioxidative effect of BL + CE was the greatest for small, dense LDL (Sd-LDL)
      with further increases in percentage of lag times 4 folds compared to BL alone.
      CONCLUSION: Our results indicate that supplementation with BL may help to
      scavenge oxygen free radicals, save the LDL-vitamin E content, and inhibit LDL
      oxidation. Furthermore, the addition of vitamins C and E to BL can inhibit the Sd
      LDL oxidation more effectively, which may protect against vascular diseases in
      type 2 diabetic patients.

PMID- 11976563
TI  - Alcohol intake and fasting insulin in French men and women. The D.E.S.I.R. Study.
AB  - BACKGROUND: To study the relation between alcohol consumption and the fasting
      insulin concentration in a French population with a range of alcohol intakes.
      METHODS: 2.406 men and 2.500 women, aged 30 to 65 years who were not known as
      diabetic and with a non-diabetic fasting plasma glucose<7.0 mmol/l were studied.
      Insulin was assayed by a specific micro-enzyme immunoassay and alcohol intake was
      from a self-questionnaire. RESULTS: Fasting insulin concentration showed an
      inverse linear association with alcohol consumption, after adjustment for age and
      possible confounding factors (p for trend<0.0001 men; p<0.002 women), with a 29%
      higher insulin in non-drinkers compared to very heavy drinkers (> 80 g/day) in
      men (p<0.0001) and a 23% and 26% difference when compared to heavy drinkers (41
      80 g/day) in men and women respectively (p<0.0001, p<0.003). This relation did
      not differ significantly according to whether the alcohol was consumed as wine,
      beer/cider or spirits. Fasting plasma glucose modified the relation between
      alcohol and insulin in men: while the negative relation alcohol-insulin was
      strong for fasting plasma glucose<6.0 mmol/l (p<0.0001), there was no association
      above 6.0 mmol/l (p=0.4). CONCLUSION: There is an inverse relation between
      alcohol consumption and fasting insulin concentrations. Some studies have found a
      U shaped relation, and this is probably due to the inclusion of diabetic
      subjects. As hyperinsulinemia has been shown to be positively associated with
      cardiovascular disease, it may be one of the variables that explains the
      protective effect of moderate alcohol consumption on cardiovascular disease.

PMID- 11976564
TI  - Clinical usefulness of corrected QT intervals in diabetic autonomic neuropathy in
      patients with type 2 diabetes.
AB  - BACKGROUND: It is recognized that QTc intervals reflect autonomic nerve function.
      To investigate the clinical usefulness of corrected QT intervals (QTc) in
      assessing autonomic nerve function in type 2 diabetes, we measured QTc intervals
      using Bazett's formula in 58 type 2 diabetic patients and 20 age-matched healthy
      subjects. METHODS: We examined relationships between QTc intervals and the
      coefficient of variation of RR intervals (CV(RR)), systolic blood pressure
      response to standing, and sympathetic skin response (SSR) whose tests reflect
      autonomic nerve function. We also studied the correlation between QTc and blood
      pressure or serum lipid concentrations. RESULTS: QTc intervals in diabetic
      patients were significantly longer than those in healthy subjects and showed a
      significant but weak negative correlation with CV(RR), as well as systolic blood
      pressure response to standing. No significant difference in QTc intervals was
      observed between patients with and without a detectable SSR. QTc intervals showed
      a significant positive correlation with systolic and diastolic blood pressure
      although it did not correlate with serum lipid concentrations. QTc also tended to
      be long in obese diabetic subjects (body mass index > 25). CONCLUSION: QTc
      intervals might also be affected by other factors such as arteriosclerotic
      macroangiopathy and obesity, and not only autonomic nerve function. Therefore it
      might be considered as an overall index for complications, and not for pure
      autonomic impairment.

PMID- 11976565
TI  - Comparison of blood glucose stability and HbA1C between implantable insulin pumps
      using U400 HOE 21PH insulin and external pumps using lispro in type 1 diabetic
      patients: a pilot study.
AB  - BACKGROUND: To assess the efficacy on blood glucose control of continuous
      peritoneal insulin infusion from implantable pump (CPII) compared with continuous
      subcutaneous infusion using insulin lispro (CSII-IL) in type 1 diabetic patients.
      METHODS: Fourteen type 1 diabetic patients (5 males and 9 women, age 50.6 +/-
      12.8, diabetes duration 28.0 +/- 13.4 years) were treated with CSII-IL and CPII.
      Capillary blood glucose (BG) was monitored and recorded at least 4 times per day
      during 2 study periods of 45 days: using CSII-IL (period A), and from 45th to
      90th day after implantation (period B). HbA1C was measured at the end of each
      period. RESULTS: Both daily BG levels (145 +/- 18 vs 153 +/- 17 mg/dl, p<0.01)
      and preprandial BG levels (139 +/- 20 vs 147 +/- 22 mg/dl, p<0.05) were lower in
      period B. Although postprandial BG values tended to be lower in period B, this
      reduction did not reach statistical significance (149 +/- 20 vs 157 +/- 16 mg/dl,
      p=0.07). Meanwhile, SD of all BG values was lower with CPII (69 +/- 11 vs 79 +/-
      17 mg/dl, p<0.01) and HbA1c levels were lower at the end of period B (7.3 +/- 0.9
      vs 7.8 +/- 0.9%, p=0.04). Low blood glucose index was comparable during both
      periods (2.8 +/- 1.6 vs 3.1 +/- 1.5, p=0.4). CONCLUSION: CPII may provide a
      better BG control and stability than CSII-IL. However, a long-term randomized
      prospective study is needed to confirm these improvements.

PMID- 11976566
TI  - Low socioeconomic status as a risk factor for gestational diabetes.

PMID- 11976567
TI  - Proliferative retinopathy in patients with type 1 diabetes of less than 5 years'
      duration.
AB  - The position statement about diabetic retinopathy postulates that at least 3-5
      years of duration of diabetes are needed for the retinopathy to occur, and
      initial retinal examination should be performed within 3-5 years after the
      initial diagnosis. We report here the case of a 18 year-old type 1 diabetic woman
      with a proliferative retinopathy discovered 2 years after the onset of a clinical
      diabetes. The hypothesis of a Latent Autoimmun Diabetes in Adults (LADA) could
      not be excluded and we propose, particularly in this context, to detect a
      diabetic retinopathy at the onset of diabetes.

PMID- 11976568
TI  - Recommendations for the diagnosis, the prevention and the treatment of obesity.

PMID- 11976569
TI  - [Fundus photography for the screening for diabetic retinopathy].
AB  - Despite the efficacy of laser photocoagulation to prevent complications of
      diabetic retinopathy, diabetic retinopathy remains a major cause of visual
      impairment and blindness in France. This is mainly due to a too late diagnosis of
      diabetic retinopathy. In an effort to detect diabetic retinopathy at an early
      stage before visual loss, international and national guidelines for the screening
      for diabetic retinopathy have been developed, which recommend annual fundus
      examination for all diabetic patients. In France, a recent survey showed that
      less than 50% of diabetic patients had had an eye examination during the previous
      year. With the increasing number of diabetic patients and the decreasing number
      of ophthalmologists, this situation should not improve by the next 15 years.
      Fundus photography is a method at least as sensitive as ophthalmoscopy in the
      screening for diabetic retinopathy. New nonmydriatic cameras and digital
      photography may allow a network organization of several screening centers around
      a central ophthalmological reading center where digital images could be
      transmitted. This organization should improve the screening for diabetic
      retinopathy, while saving medical time.

PMID- 11976573
TI  - [Carbon dioxide pneumoperitoneum and peritoneal carcinosis: review].
AB  - OBJECTIVE: The aim of this work was to demonstration the relations between CO(2)
      laparotomy and peritoneal carcinosis. The first part of this review presents
      published observations of disseminated peritoneal carcinosis after laparoscopy
      with CO(2) insufflation. The second part deals with the possible effects of CO(2)
      laparoscopy on the mechanism of carcinosis. MATERIAL AND METHODS: We made a
      Medline search for cases of peritoneal dissemination after CO(2) laparoscopy. We
      present here the published results as well as data from comparative studies
      conducted in humans and animals on the effects of each step of CO(2) laparoscopy
      on carcinogenesis and the progress of carcinosis. RESULTS: Most of the published
      cases on peritoneal dissemination after CO(2) laparoscopy concerned management of
      ovarian carcinomas where malignancy was not diagnosed before the operation and
      not treated immediately with laparotomy. The significance of peritoneal
      dissemination appears to be related to the delay between laparoscopy and
      laparotomy. No comparative study in humans has been published. For animal
      studies, it has been difficult to design valid animal modes. Those we present
      show that laparoscopy has no negative influence on tumor growth but that it may
      affect peritoneal dissemination. Laparoscopy can participate in diffusion of
      tumor cells either due to repeated manipulation with contaminated instruments or
      because of the insufflation itself. These cells can be seeded on traumatized
      areas of the peritoneum or parietal wall or on the port tracts. The recent work
      by Volz has proven the effect of CO(2) which can cause a change in the ultra
      structure of the peritoneum. This may facilitate peritoneal seeding of the
      malignant cells. No other study has shown any evidence of increased
      intraperitoneal tumor growth. Only primary results of post-laparoscopy liver
      metastasis have diverged. Laparoscopy does not seem to have a negative effect on
      general immunity, but possible changes in intraperitoneal immunity remain to be
      elucidated. CONCLUSION: Observations concerning peritoneal dissemination are
      found in cases where CO(2) insufflation was used for laparoscopy, but no studies
      have proven certain risk greater for laparoscopy than for laparotomy. Maximum
      precautions must be taken during the management of suspicious ovarian lesions.

PMID- 11976574
TI  - [Cervical cancer in Bas-Rhin: trend and prediction of the incidence in 2014].
AB  - BACKGROUND: In the world, the cervix cancer is the second commonest cancer in
      women. Its incidence is decreasing but it is still too frequent. The aim of this
      study was to predict the incidence of cervix cancer among women in the Department
      of Bas-Rhin. METHODS: Incidence data were provided by the Bas-Rhin Tumor
      Registry. The incidence of in situ tumors and invasive cancers was predicted in
      2010-2014 by using an age - period - cohort model and a Bayesian approach.
      RESULTS: The incidence rates predicted by the model, standardized to the European
      population, were 99.7 per 10(5)population in 2000-2004 (CI 95%: [82.7-118.5]) and
      177.1 per 10(5) population in 2010-2014 (CI 95%: [103.7-288.5]) for in situ and
      13.0 per 10(5) population (CI 95%: [9.5-17.2]) in 2000-2004 and 11.1 per
      10(5)population (CI 95%: [4.5-22.7]) in 2010-2014 for invasive tumors.
      CONCLUSIONS: The decrease of invasive tumors is due to screening. The improvement
      of the quality of the screening and treatment of in situ tumors would allow the
      number of incident cases of cervix cancer to decrease.

PMID- 11976575
TI  - [Squamous cell carcinoma of the breast review of the literature: illustrated by
      the report of a case].
AB  - We report the case of 37-year-old women with primary Squamous cell carcinoma of
      the right breast. The tumor was nodular, 13cm, with important hemorrhagic and
      necrotic reshaping. There was no central or peripheral cystic altering.
      Histologically, the tumoral cells were polyedric, dyskeratosic with intercellular
      junction. This rare breast entity has controversy histogenesis. The development
      was characterized by metastases frequency. The treatment remains no codified.

PMID- 11976576
TI  - [Why a special issue for maternal health in French speaking Africa?].

PMID- 11976577
TI  - [Determinants of risk factors associated with severe maternal morbidity:
      application during antenatal consultations].
AB  - In order to assess the incidence of severe maternal mortality (SMM) and search
      for associated determinants of risk factors, a population-based survey of 20,326
      pregnant women was conducted in six counties in West Africa (MOMA study).
      Complete files were available for 19,545 (96.2%) women. The rate of SMM, assessed
      with an overall indicator, was 6.7% (5.7-6.4). The relationship between SMM and
      various socio-economic features, gyneco-obstetrical antecedents and
      characteristics of the current pregnancy was studied. Multivariate analysis
      identified 10 factors of risk of SMM. Prevalence, adjusted odds-ratio, positive
      predictive value and adjusted attributable risk were determined for these ten
      factors. By decreasing order of positive predictive value, these factors were:
      hemorrhage during pregnancy (51.5%), antecedent cesarean (27.1%), high blood
      pressure (diastolic pressure 10 (18.9%), systolic pressure 14 (14.6%)),
      antecedent multiple pregnancy (15.8%), height 150 cm (12.9%), lack of fetal
      movements (12.6%), history of 3 stillborns (9.3%), age over 35 years (8%),
      nulliparity (7.3%), presence of disease during the pregnancy (7.1%). These
      results show the importance of antenatal consultation during which these factors
      are easily identifiable.

PMID- 11976578
TI  - [Dystocia: frequency and risk factors in seven areas in West Africa].
AB  - OBJECTIVES: 1) To measure the incidence of dystocia in six cites and one rural
      area in West Africa. 2) To identify risk factors of dystocia and analyze their
      interrelationships with the goal to potentially use them to identify high-risk
      pregnant women attending antenatal consultations. (3) To assess their usefulness
      as predictors of dystocia during pregnancy. METHODS: The MOMA study is a
      prospective population-based follow-up study of 20,326 pregnant women in West
      Africa. Due to the likely diagnostic and recall bias for home deliveries, risk
      factors for dystocia were analyzed only for deliveries in health facilities. A
      total of 16,318 deliveries were analyzed. RESULTS: The incidence of dystocia was
      18.3% (95%CI: 17.7-18.9). Multivariate analysis using stepwise logistic
      regression disclosed the following significant risk factors: short stature,
      scarred uterus, nulliparity. Positive predictive values were very low for both
      univariate and multivariate analysis. CONCLUSION: The incidence of dystocia,
      which occurs mainly at delivery, is high in West Africa. Consequences are often
      dramatic, both for the fetus and the mother. None of the risk factors studied,
      even when used in combination, provided a good prediction of dystocia. All
      pregnant women should therefore be considered at risk of dystocia. Efforts should
      be made to detect dystocia during labor (partography) and to provide good-quality
      emergency obstetric care. Emergency obstetric care must be made available to all
      pregnant women. This goal can be achieved in most of the major West African
      cities. More facilities offering good-quality cesarean section must be made
      available.

PMID- 11976579
TI  - [Can clinical risk factors for perinatal mortality in West Africa be detected
      during antenatal care or during labor?].
AB  - INTRODUCTION: Perinatal mortality (PNM) is a public health problem in West
      Africa. Aims. To evaluate the rate of PNM in 6 countries of West Africa, to
      identify clinical risk factors for PNM, to quantify the relative contribution of
      antenatal care and labor survey in the detection of these risk factors. METHODS:
      The MOMA study was a prospective population-based study that collected data about
      20326 pregnant women in various, primarily urban, areas of Burkina-Faso, Ivory
      Coast, Mali, Mauritania, Niger and Senegal. The present report analyses 19.870
      singleton births and 31 simple clinical variables. RESULTS: The mean PNM ratio
      was 42 per 1000 total births. In the crude analysis, after adjustment or taking
      prevalence into account, the principal risk factors were: immediately antenatal
      and intrapartum vaginal bleeding, labor hypertension, dystocia and infection.
      CONCLUSION: The PNM are very high in West Africa. The principal risk factors for
      PNM can be detected only during labor.

PMID- 11976580
TI  - [Maternal morbidity and qualification of health-care workers: comparison between
      two different populations in Senegal].
AB  - OBJECTIVE: High fertility rates and high maternal mortality ratios have led most
      cooperation agencies to place high priority on health of women and children. The
      objective of this study was to compare maternal morbidity and mortality tin two
      populations with widely contrasting availability of health care in order to test
      the hypothesis that differences in maternal outcome mainly result from the
      qualification of health carers. METHODS: This population-based study included a
      cohort of pregnant women which was part of a multicenter study of maternal
      morbidity in six countries in West Africa (MOMA). We compared health outcome in
      two different populations of Senegal (Saint-Louis and Kaolack).3,777 pregnant
      women were follow through pregnancy, delivery and pureperium. Maternal morbidity
      was assessed from the women's recall at each visit of the investigator and from
      obstetric complications diagnosed by the birth attendant within health
      facilities. RESULTS: Maternal mortality was higher in the Kaolack area where
      women gave birth mainly in district health care centers, most often assisted by
      traditional birth attendants, than in Saint-Louis where women giving birth in
      health facilities were principally referred to the regional hospital and were
      generally assisted by midwives (874 and 151 maternal deaths per 100,000 live
      births respectively, p<0.01). Diagnosed maternal morbidity, however, was higher
      in Saint-Louis than in the Kaolack area, especially for births in health
      facilities (9.50 and 4.84 episodes of obstetric complications per 100 lie births
      respectively, p<0.01). Univariate and multivariate analyses showed that diagnosed
      morbidity was mainly associated with degree of training of the health attendant
      in facility deliveries and that antenatal care had no effect. DISCUSSION:
      Midwives in health facilities appear to detect more obstetric complications than
      traditional birth attendants. Immediate detection leads to immediate care and to
      a lower case-fatality rate. This could explain the differences in maternal
      outcome between two urban centers with contrasting health care availability.
      CONCLUSION: These results suggest that one of the strongest weapons in the fight
      against maternal mortality is the employment of the most qualified personnel
      possible for monitoring labor.

PMID- 11976581
TI  - [Maternal mortality in West Africa: risk, rates, and rationale].
AB  - New information has been collected about maternal mortality which is becoming
      better known in the West African countries. However, estimated rates for these
      countries still exhibit wide discrepancies related to the methods used. The
      purpose of the present work was to describe the principal methods which can be
      used to estimate rates and to present the results observed in the six countries
      of the MOMA survey. Obstetrical causes of maternal death and their substandard
      care, pointed out by the audit carried out during the survey, are presented and
      discussed.

PMID- 11976582
TI  - [Potential role of prenatal care in reducing maternal and perinatal mortality in
      sub-Saharan Africa].
AB  - Prenatal care has been implemented in developing countries according to the same
      mode as applied in industrialized countries without considering its real
      effectiveness in reducing maternal and neonatal mortality. Several recent studies
      suggest that the goals should be revisited in order to implement a program of
      prenatal care based on real scientific evidence. Based on the current literature,
      we propose a potentially effective content for prenatal care adapted to the
      context of developing countries. Four antenatal consultations would be enough if
      appropriately timed at 12, 26, 32 and 36 weeks pregnancy. The purpose of these
      consultations would be: 1) to screen for three major risk factors, which, when
      recognized, lead to specific action: uterine, scare, malpresentation, premature
      rupture of the membranes; 2) to prevent and/or detect (and treat) specific
      complications of pregnancy: hypertension, infection (malaria, venereal disease,
      HIV, tetanus, urinary tract infection); anemia and trace element deficiencies,
      gestational diabetes mellitus; 3) to provide counseling, support and information
      for pregnant women and their families (including the partner) concerning: severe
      signs and symptoms of pregnancy and delivery, community organization of emergency
      transfer, delivery planning. These potentially effective actions can only have a
      real public health impact if implemented within an organized maternal health
      system with a functional network of delivery units, if truly quality care is
      given, and if the relationships between health care providers and the population
      are based on mutual respect. Sub-Saharan African women use prenatal care
      extensively when it is accessible; this opportunity must be used to implement
      evidence-based actions with appropriate and realistic goals.

PMID- 11976583
TI  - [Training midwives in developing countries in obstetric ultrasonography: goals
      and application].
AB  - Obstetric ultrasonography is one of the most important advances in antenatal and
      obstetric emergency care. As part of the program designed to reduce maternal and
      perinatal mortality, it can provide real patient benefit and should become a
      standard procedure in developing countries. The midwife is the ideal health
      worker to practice first level obstetric ultrasonography. Appropriate material
      can be procured and of specific training can be organized at a moderate cost.
      Several difficulties are encountered, but there is a solution for each. The
      concept of the training program is particularly important.

PMID- 11976584
TI  - [Estimate of expected cesarean section rate for maternal indications in a
      population of pregnant women in West Africa (MOMA survey)].
AB  - OBJECTIVES: There is still some debate about the optimal rate of cesarean section
      (CS) needed to achieve better outcome for both mothers and infants in developing
      countries. We examine here two aspects of the question: i) a simple method to
      estimate the expected rate of CS according to obstetrical risk; ii) a test of the
      method to estimate the appropriate rate for maternal indications in a general
      population of pregnant women in West Africa. METHODS: This population-based study
      was conducted in a cohort of pregnant women in six West African countries (MOMA
      survey): Abidjan (Ivory Coast), Bamako (Mali), Niamey (Niger), Nouakchott
      (Islamic Republic of Mauritania), Ouagadougou (Burkina Faso), and in three areas
      of Senegal, two small towns (Fatick and Kafrine, Kaolack region), and one major
      city (Saint-Louis). 19,459 women with singleton pregnancies with expected breech
      presentation were followed to delivery and puerperium. Maternal indications for
      CS were defined as dystocia (prolonged labor over 12 hours), malpresentation,
      previous cesarean section, abruptio placentae, placenta paevia and eclampsia. A
      standardized method was used to calculate the number of expected CS in the MOMA
      population, according to the level of the obstetrical risk. RESULTS: The minimal
      needs for Cs for maternal indications were estimated between 3.6 and 6.5 per 100
      deliveries. However, we observed a rate of 1.3 CS per 100 deliveries. DISCUSSION:
      These findings underline the lack of CS for maternal indications in urban West
      Africa. The method of standardization we propose could help policy makers, health
      planners and obstetricians to design programs to reach the appropriate level of
      CS and to monitor and follow-up these programs.

PMID- 11976587
TI  - [Genetic aspects of epilepsy: current knowledge and perspectives].
AB  - Rapidly advancing knowledge concerning the genetic aspects of epilepsy have led
      us to complete a recent article on the subject published in the journal. A
      contrasting picture is emerging, particularly between symptomatic and idiopathic
      epilepsy. For symptomatic epilepsy, divers gene products implicated in brain
      development and neuron survival have been identified. Inversely, for idiopathic
      epilepsy, the latest discoveries confirm their canalopathic nature. In addition,
      rapid progress in the field of mendelian inherited epilepsy has pointed out the
      lack of notable progress concerning common epilepsy with a complex hereditary
      pattern. These forms are one of the major challenges for genetic analysis of
      epilepsy.

PMID- 11976588
TI  - [Critical illness neuropathies].
AB  - A number of patients admitted to intensive care units for non-neurological
      disorders develop neuromuscular complications. These patients present with an
      acute flaccid generalized weakness that may or may not be accompanied by sensory
      symptoms. There are two main conditions, namely critical illness polyneuropathy
      and neuromuscular disorder related to the use of neuromuscular blocking agents.
      These conditions differ in several ways. Critical illness polyneuropathy occurs
      usually after long stays (weeks) in intensive care units. It concerns patients
      presenting with a multiple organ dysfunction syndrome, and often sepsis. The
      polyneuropathy is axonal and implies both sensory and motor fibres. Its
      pathophysiology remains unclear. Mortality is as high as 60 p.cent and relates to
      the medical, rather than to the neurological condition. In survivors recovery may
      be complete, although over a period of months. Neuromuscular disorder related to
      the use of neuromuscular blocking agents occurs on average after 10 days. It most
      often concerns patients admitted to intensive care units for acute respiratory
      failure, mainly asthma or adult respiratory distress syndrome, that may require
      mechanical ventilation, use of neuromuscular blocking agents and steroids. A
      purely motor deficit is usually first noticed when curarisation is discontinued.
      Electromyography discloses fibrillation potentials in all muscles, as well as
      myopathic changes. Muscle biopsy demonstrates necrosis and a deficit in myosin
      filaments. In severe cases, injury to distal motor axons probably occurs.
      Recovery is usually excellent over a few weeks. Recently, replacement of
      neuromuscular blocking agents by sedatives has notably reduced the occurrence of
      this disorder. Critical illness neuropathies often cause difficulty in weaning
      patients from the respirator. They prolong the stay in the intensive care unit,
      thereby increasing the risks of complications for the patients. Course of these
      neuromuscular disorders is usually favorable, however sometimes with sequelae.

PMID- 11976590
TI  - [Alzheimer's disease: a public health problem: yes, but a priority?].
AB  - Alzheimer's Disease is a major Public Health problem for many reasons. First, it
      is a frequent disease since, in France, the prevalence was estimated at about
      400.000 cases, and the annual incidence at 100.000 cases. The frequency of the
      disease increases, in particular due to the ageing of the population. This
      disease has major consequences on the life of the patient and his/her caretaker.
      The cost of the disease is important, estimated at about 50 milliards of French
      francs. Pharmaceutical treatment and other interventions are possible in
      particular to delay the nursing home placement. On the other hand, this disease
      is often ignored, under-diagnosed, underestimated and exposed to inequality in
      resorting to care. In summary, Alzheimer's Disease (AD) has all the criteria
      required for a major public health problem. In spite of this observation, AD is
      not yet considered as a priority for health authorities, although attitudes are
      changing.

PMID- 11976591
TI  - [Variability of right hemisphere activation during semantic word processing in
      aphasic patients: an electrophysiologic study in three patients].
AB  - After stroke, the interhemispheric reorganisation of the neural network
      implicated in language is hypothesized to be a function not only of the site of
      lesion but also of the residual impairment. With a multiple case approach, we
      tested this hypothesis in three chronic aphasic patients. Two patients, GE
      (capsulo-lenticular stroke) and JHN (fronto-temporal stroke) showed formal
      residual semantic difficulties, while the third patient (EG, large sylvian
      lesion) did not. Brain electric activity was analysed during a categorisation
      task of tachistoscopically presented words in the left and the right visual
      field. The temporal analysis of brain activity showed that both patients with
      semantic residual difficulties activated the right hemisphere (RH) during some
      steps of word processing. In the third patient, without semantic impairment, the
      RH was activated only during a short time period. Further more, RH activation was
      shown to be dependent on the visual field of word presentation. Phonological
      impairment was not predictive of RH activation. These results suggest that RH
      activation, particularly anterior regions, can occur during semantic processing
      of words as a function of semantic residual impairment.

PMID- 11976589
TI  - [Immunopathology and treatments of Guillain-Barre syndrome and of chronic
      inflammatory demyelinating polyneuropathy].
AB  - The concepts of Guillain-Barre syndrome (GBS) and chronic inflammatory
      demyelinating polyneuropathy (CIDP) have changed over the last decade. The
      spectrum of GBS ranges from acute inflammatory demyelinating polyneuropathy to
      pure motor, sensory-motor or bulbar variants and the Miller Fisher syndrome. Also
      CIDP includes different variants in addition to the typical clinical picture with
      symmetrical proximal and distal weakness, such as a form with predominant distal
      weakness, a pure sensory form, an asymmetric form and a form with predominant
      cranial nerve involvement. Detailed immunopathologic features have been described
      in GBS and CIDP: most current investigations are centered on the hypothesis of
      molecular mimicry in GBS and together with the pathogenic role of cell-mediated
      immunity different antibodies have been discovered in GBS which interfere with
      nerve impulse conduction on neuromuscular transmission. The immunopathogenesis of
      CIDP remains fragmentary and insufficient for a unified hypothesis. Activated
      macrophages and T-cells with the participation of T-1 helper cell related
      cytokines seem to play a fundamental role in demyelination. The nature of antigen
      presenting cells, T-cell receptors, adhesion molecules and the proinflammatory
      cytokines need to be explored to design more specific immunotherapies.
      Established treatments in GBS include intravenous immunoglobulin and plasma
      exchange. Randomized trials have shown the efficacy of prednisone, intravenous
      immunoglobulin and plasma exchange in CIDP. New insight in the pathogenetic role
      of the cytokine-network in CIDP opens new therapeutical possibilities with the
      modification of the T-1 helper cell reaction with interferon.

PMID- 11976592
TI  - [Metamemory and Parkinson's disease].
AB  - Metamemory is a multifaceted concept, which deals with the individual's knowledge
      and control of his or her own memory system. One metacognitive ability that has
      considerable importance in everyday life is the ability to control his or her own
      memory. In this study, we have examined whether Parkinson's disease affects the
      degree to which a person allocate study time. 17 Parkinson subjects and 18 older
      controls participated in this study. Parkinson subjects and control subjects made
      a readiness recall task in which subjects monitor themselves the learning
      procedure, allowing to measure metamemory control (study time by item). Control
      subjects were found to take more time in study than parkinson subjects. The lists
      were learned under two condition: a self-paced condition in which subjects could
      study each word as long as they would and an experimenter-paced condition. The
      analysis revealed that control subjects recalled more items than parkinson
      subjects only in the self-paced condition. These results suggested that Parkinson
      related differences in the allocation of study time mediate a part of Parkinson
      related differences in memory performance.

PMID- 11976593
TI  - [Characterization and discrimination of kinetic tremor in Parkinson's disease].
AB  - Kinetic tremor recorded with a laser system during a compensatory tracking task
      of the index finger was analyzed in 21 patients with PD whose tremor amplitude
      was between low and moderate, and 30 control subjects. Nine characteristics
      quantifying the tracking task and tremor including mean tracking error, reaction
      time, peakedness, harmonicity, median frequency, proportional power in the 3-4
      Hz, 4-6 Hz and 7-12 Hz ranges, and power at 0.25 Hz, were applied to the
      processed signal. The discriminating power of each characteristic was evaluated
      using differences between group means (p values), maximum percentage
      discrimination, and number of outliers in the patient group using z-score and
      96.7(th) percentile of the control group. All nine characteristics showed
      significant differences between means of the two groups using Welch-modified t
      tests for unequal variances. The most discriminating characteristics reflected
      differences in the frequency distribution of the movement and did not correlate
      highly with postural tremor amplitude nor with clinical ratings of tremor.
      Discrimination methods classified correctly up to 66.7 p.cent of the patients.
      Combining representative information about proportional power during posture and
      tracking gave a much higher discrimination (90 p.cent) with respect to the 96.7th
      percentile of the control group. These results suggest that by combining
      information coming from postural and kinetic tremors it is possible to isolate a
      specific aspect of PD symptomatology which could be used to reevaluate the
      classic distinction made between the akineto-rigid and tremulous forms of PD
      independently of tremor amplitude.

PMID- 11976594
TI  - [Primary progressive forms of multiple sclerosis: application of the new
      diagnostic criteria in French].
AB  - Approximately 15 p.100 of all cases of multiple sclerosis (MS) are primary
      progressive multiple sclerosis (PPMS). Diagnosis is however frequently delayed
      due to the lack of relapse. The commonly used Poser criteria established in 1983
      are not directly applicable to this subgroup of MS patients. In 2000, Thompson et
      al proposed new diagnostic criteria for PPMS. The aim of our study was to apply
      retrospectively these new criteria to a cohort of patients from northern France
      (G-SEP cohort). The cohort included 184 patients (94 women and 90 men, sex
      ratio=1.04). Mean age at disease onset was 40.3 years (18-67 years) and mean
      follow-up was 9.9 (1-39 years). Only one patient was older than 65 years but 13
      patients (7.1 p.100) were younger than 25 years. Patients were classed as having
      definite, probable or possible PPMS on the basis of clinical, MRI, cerebrospinal
      fluid and visual evoked potential (VEP) data. Most of the patients (61.4 p.100)
      had one symptom at onset; spastic paraparesis was frequent (79 p.100). Mean delay
      to diagnosis was 4.4 years. Ten patients (5.4 p.100) were surgically treated for
      cervic arthrosic myelopathy. Mean EDSS score at the end of follow-up was 5.8 (3
      10). MRI was positive in 87.3 p.100 of the patients. Oligoclonal bands were found
      in 78.2 p.100. VEPs ware abnormal in 79.9 p.100 of the patients. Applying the
      Thompson criteria, 57.7 p.100 of the patients had definite PPMS, 38.7 p.100
      probable PPMS. Our results are very similar to previous studies and confirm the
      usefulness of the new proposed criteria, which however should be prospectively
      tested to determine sensitivity and specificity in a new cohort of patients.

PMID- 11976595
TI  - [Aneurysm of the anterior cerebral artery disclosed by unique hemianopic
      scotoma].
AB  - We report the case of a 47-year-old man with an aneurysm of the anterior cerebral
      artery revealed by lateral homonymous hemianopic non congruent scotoma. The
      aneurysm was successfully treated with interventional radiology procedures. In
      10p. cent of cases, intracranial aneurysms present prior to their rupture with
      headache or neuro-ophthalmological symptoms and signs. Isolated visual field
      defects are rare, and isolated compression of the optic tract is extremely
      unusual. Although rare, the development of a non-congruent controlateral
      homonymous hemianopic scotoma is highly suggestive of optic tract compression,
      and can be explained by the somatotopy of the fibers within the optic tract.

PMID- 11976596
TI  - [Toxocara canis meningoradiculitis].
AB  - Various neurological pictures attributed to human toxocariasis are sparsely
      reported in the literature. A case of toxocaral infection presenting as
      meningoradiculitis is described herewith. Etiological diagnosis was oriented by
      the finding of an eosinophilia in the spinal fluid, then confirmed by the result
      of the immunodiagnosis of toxocariasis from both serum and spinal fluid.

PMID- 11976598
TI  - [Chronic polyradiculoneuritis disclosing sarcoidosis].
AB  - Peripheral Nervous System (PNS) involvement occurs in 10 to 40 percent of
      patients presenting with sarcoidosis. Axonal polyneuropathies and
      mononeuropathies are the most frequently reported whereas acute or chronic
      polyradiculoneuritis are rarely described. We report the case of a 54 year-old
      woman admitted for a progressive sensorimotor deficit of the lower limbs.
      Bilateral ocular redness corresponding to an uveitis was also observed.
      Neurological examination and electrophysiological data were consistent with a
      chronic polyradiculoneuritis. The neurological status of the patient improved
      after six months of treatment with oral corticotherapy associated with
      immunosuppressive treatment. Our case allows a review of the literature
      concerning PNS involvements and treatments in sarcoidosis.

PMID- 11976597
TI  - [Parsonage-Turner syndrome and giant-cell arteritis].
AB  - Parsonage-Turner syndrome is an idiopathic brachial neuropathy affecting the
      5(th) and the 6(th) roots. Giant-cells arteritis rarely affects the brachial
      plexus. In such cases, it can mimic Parsonage-Turner syndrome. We report a case
      focusing on clinical signs suggesting giant-cell arteritis.

PMID- 11976599
TI  - [Acute polyradiculoneuropathy after Chlamydia pneumoniae infection].
AB  - A 36-year-old woman presented acute polyradiculoneuropathy following Chlamydia
      pneumoniae infection. Although electrophysiologic studies were normal, clinical
      features were typical of Guillain-Barre syndrome (GBS). Anti-ganglioside GM1
      antibodies were positive. Two other cases of GBS following Chlamydia pneumoniae
      infection have been reported, but no specific feature emerges. Outcome was good
      in our patient after intravenous globulin then antibiotic therapy. Our case
      supports the notion that Chlamydia pneumoniae infection can induce GBS. The
      association is probably underestimated.

PMID- 11976600
TI  - Nerve ischemia in Guillain-Barre syndrome: an alternative mechanism for early
      conduction failure.

PMID- 11976602
TI  - [Akinetic mutism and anterior bicerebral infarction due to abnormal distribution
      of the anterior cerebral artery].

PMID- 11976601
TI  - [Seizures and recurrent left hemiparesia (clinical conference)].

PMID- 11976603
TI  - [Quantitative analysis techniques for brain MRI: applications in multiple
      sclerosis].

PMID- 11976604
TI  - Hypothesis: preeclampsia as a maternal-fetal conflict.

PMID- 11976605
TI  - Medscape Espana: speech given on September 12, 2001, in Madrid, Spain,
      celebrating the launch.

PMID- 11976606
TI  - Case report: Dr. Lecter's convulsive syncope.

PMID- 11976607
TI  - American health system reform: circa 2001-2002.

PMID- 11976608
TI  - Medscape goes to Japan in Japanese: continuing the tradition online.

PMID- 11976609
TI  - Appreciation for your editorial.

PMID- 11976610
TI  - Culture of death.

PMID- 11976612
TI  - Multislice CT: technical principles and clinical applications.
AB  - The aim of this article is to describe the main technical differences between
      multi-slice Computed Tomography (CT) and spiral CT. We also briefly discuss the
      diagnostic benefits of this new technology which consolidates and expands on the
      results achieved with spiral CT in the 90s. More specifically, gantry speed and
      improved spatial resolution in the z axis considerably expand angiographic and
      cardiac applications, allow high-quality multiplanar and 3D reconstructions, and
      introduce CT in organ perfusion studies (particularly those of heart and brain).

PMID- 11976613
TI  - Role of HRCT in the identification of atypical pulmonary mycobacteriosis.
AB  - AIM: 1) To identify the principal radiological signs of atypical pulmonary
      mycobacteriosis by means of X-rays and CT/HRCT; 2) to compare the two methods in
      order to evaluate their reliability with particular interest for the diagnostic
      role of HRCT in the identification of the disease; 3) to establish any
      significant differences in the pathology between AIDS and immunocompetent
      patients. MATERIAL AND METHODS: The chest X-rays and CT/HRCT of 28 atypical
      pulmonary mycobacteriosis patients (16 with AIDS and 12 immunocompetent) have
      been studied. The subjects were examined during the period of October 1993 to May
      2000 and were found to be positive for atypical mycobacterium and consequently
      underwent a standard chest X-ray. Twenty cases were followed-up with a chest
      CT/HRCT; of these only 17 were performed within 30 days of the traditional chest
      X-ray which was considered to be the time limit in order to validate the
      comparison between the two methods. RESULTS: The significant semeiotical findings
      were the parenchymal consolidations observed in 25 patients (89%) by standard
      chest X-rays; the CT/HRCT confirmed the findings in 4 cases while in 13 it
      enhanced the evaluation of their extensions. In 9 cases the standard chest X-ray
      established the presence of cavitations which were confirmed by the CT/HRCT in
      only 7 cases. Lymphadenopathy was observed in 3/28 patients (10.7%) through
      standard X-rays and in 15/17 cases (82%) through CT/HRCT. The latter method
      revealed to be extremely useful in the identification of this pathology. Nodules
      and micronodules were seen in 5 patients with traditional X-rays and in 9 cases
      with CT/HRCT. Bronchogenic spread signs of disease became visible only with CT
      and in particular with HRCT (11/17 patients = 65%). Comparing the two groups
      (AIDS and immunocompetent) taken into consideration, the most frequent lesion
      present in both was parenchymal consolidation resulting more bilateral in the
      AIDS subjects. Cavitation and pleural edema were seen more often in the AIDS
      group while bronchiectasia, bronchogenic spread and signs of previous pleuro
      parenchymal suffering were more frequent in the immunocompetent patients.
      Lymphadenopathy was frequently found in the total study population but appeared
      slightly prevalent for the group not afflicted with AIDS. CONCLUSION:
      Radiological study of the chest permitted the identification of signs useful in
      the diagnosis of mycobacteriosis in all the patients studied. The application of
      CT/HRCT added helpful elements in almost all of the cases examined demonstrating
      to be more effective than the standard chest X-ray not only in terms of improved
      evaluation of known lesions but also in the identification of lesions which are
      difficult to determine by means of traditional radiology.

PMID- 11976614
TI  - Diffuse liver disease. Evaluation with CT and MR imaging.

PMID- 11976615
TI  - Multiphase multislice spiral CT for liver assessment: optimization in cirrhotic
      patients.
AB  - PURPOSE: The aim of our study was to optimize a multiphase study protocol with
      double arterial phase acquisition in a patient population with cirrhosis using a
      multislice spiral CT scanner. MATERIAL AND METHODS: Thirteen patients (10 males,
      3 females, mean age 58 years) with known cirrhosis were selected for the study.
      All examinations were performed with a multislice spiral CT scanner (Somatom Plus
      4 Volume Zoom; Siemens, Erlangen, Germany). Images were acquired using the
      following parameters: slice collimation, 2.5 mm; slice thickness, 3.0 mm; table
      feed, 10.8 mm/sec; mAs, 165; kVp, 120. Four scans of the hepatic parenchyma were
      obtained after the administration of contrast material. The first pass (early
      arterial phase) was acquired in a cranio-caudal direction; the second pass (late
      arterial phase) was acquired in a caudo-cranial direction. Early and late
      arterial phases were obtained during a single breath-hold of 24 sec. The third
      pass (portal-venous phase) was acquired with a 60-sec delay time after contrast
      material injection. The fourth pass (equilibrium phase) was obtained with a 180
      sec delay time. Optimal delay time to start CT acquisition was assessed by means
      of injecting a 20-ml minibolus of contrast material and by performing serial
      dynamic scans every two sec at the level of the hepatic hilum. The time of peak
      aortic enhancement was used as the start time for the early arterial phase.
      Attenuation values of aorta, portal vein, and liver parenchyma were calculated in
      all the acquisitions. CT data from the early arterial phase were used to produce
      three-dimensional angiographic images of the hepatic and mesenteric circulation.
      RESULTS: The enhancement of liver parenchyma progressively increased from pre
      contrast phase to portal-venous and equilibrium phases. The highest difference in
      attenuation values between aorta and hepatic parenchyma was observed during the
      second acquisition (early arterial phase, 247.78+/-106.29 HU) rather than during
      the third acquisition (late arterial phase, 185.72+/-109.23 HU); this difference
      was statistically significant (p<0.01). DISCUSSION: Results from our study
      emphasize the potential of multiphase acquisition in the evaluation of cirrhotic
      patients; in particular, the use of an early arterial phase is useful for
      studying the hepatic and mesenteric vascular anatomy, whereas the late arterial
      and the portal-venous phases are of paramount importance for adequate evaluation
      of liver parenchyma and focal lesions. Further studies are needed to evaluate
      whether the benefits deriving from double arterial phase acquisition would
      justify the increase in cost and patient radiation exposure.

PMID- 11976616
TI  - Extrahepatic recurrence and second malignancies after treatment of hepatocellular
      carcinoma: spectrum of imaging findings.
AB  - PURPOSE: To describe diagnostic imaging features (with a focus on CT findings) of
      extrahepatic relapses of treated hepatocellular carcinoma and to propose a post
      treatment follow-up protocol. MATERIAL AND METHODS: During a six-year span, 226
      patients (aged 32-88 years) with chronic hepatitis/cirrhosis were diagnosed as
      having hepatocellular carcinoma confined to the liver and treated percutaneously
      with radiofrequency (RF) ablation. A total of 313 treatment sessions were
      performed. Post-therapeutic follow-up is based upon clinical evaluation,
      laboratory and imaging (with CT holding the key role) studies. RESULTS: Mean
      duration of follow-up was 17 months. After successful treatment, actuarial
      probability of neoplastic relapse is 30.7% after 1 year and 58.5% after 2 years.
      Eighty-eight patients had recurrence of hepatocellular carcinoma after a variable
      time interval (mean 7.3 months). Extrahepatic neoplastic relapse was observed in
      14 patients, half of these without active hepatic disease. Distribution of
      extrahepatic sites of recurrence was as follows: abdominal lymph nodes (6 cases),
      bone (3), peritoneum (2), adrenal (2), lung (1). Five patients (2.2%) had a
      second primary neoplasm. CONCLUSIONS: Extrahepatic hepatocellular carcinoma is
      uncommon and occurs in advanced stages, but may represent a pattern of post
      treatment relapse. The distinctive hypervascularity of this tumour histology may
      be observed in adenopathies and adrenal metastases. Second primary neoplasms
      should be considered in the differential diagnosis of lesions observed during
      follow-up.

PMID- 11976617
TI  - Pictorial essay: magnetic resonance imaging of adrenal masses.
AB  - In many cases, adrenal lesions are incidentally discovered during ultrasonography
      or computed tomography in the staging or follow-up of patients with primary
      malignancies. The most important issue in the radiological management of adrenal
      masses is the differential diagnosis between benign and malignant lesions.
      Magnetic resonance (MR) plays an important role in the characterization of such
      lesions. Our aim was to present the MR techniques and to review the MR features
      of most common adrenal masses.

PMID- 11976618
TI  - Transperineal sonography guided biopsy of the prostate: critical review of 1107
      cases.
AB  - PURPOSE: To assess the predictive value for a positive biopsy of different
      indicators (rectal examination, transrectal ultrasonography, total PSA, PSA
      density). MATERIAL AND METHODS: Positive predictive value was assessed on 1107
      consecutive US-guided transperineal biopsies performed from 1991 to 2001
      (cancer=344, dysplasia (PIN)=64, atypical hyperplasia=4, benign hyperplasia=686,
      inadequate=9) with univariate and multivariate analysis. RESULTS: Increasing age
      (chi square for trend 52.2, p <0.001), positive rectal examination (chi square
      233, df=1, p<0.001) or ultrasonography (chi square 191, df=1, p<0.001), total PSA
      (chi square for trend 68.9, p<0.001) and PSA density (cutoff 0.15, chi square
      104, df=1, p<0.001; cutoff 0.20, chi square 104, df=1, p<0,001) were all
      significantly associated to the likelihood of a positive biopsy outcome.
      Multivariate analysis stresses the independent role of Psa density over total
      PSA. If the parameters studied had determined the biopsy, spared benign biopsies
      [positive rectal examination=505 (66%), positive ultrasonography=467 (61%),
      PSA>4=124 (16%), PSA>10=159 (74%), PSA density >0,15=426 (62%), PSA density
      >0.20=517 (75%)] would not have justified the amount of delayed cancer biopsies
      [positive rectal examination=103 (29%), positive ultrasonography=55 (15%),
      PSA>4=42 (12%), PSA>10=569 (46%), PSA density >0,15=73 (25%), PSA density
      >0,20=107 (37%)]. CONCLUSIONS: The parameters currently available prior to
      biopsy, if used alone, allow no reliable prediction of biopsy outcome. Positive
      predictive value, particularly for PSA density, allows a better evaluation of
      biopsy indication, particularly for random sextant biopsies in the 4-10 ng/ml PSA
      range, which are frequently negative.

PMID- 11976619
TI  - Evaluation of the resistive index (RI) for the diagnosis of acute renal rejection
      in renal allografts from the same donor.
AB  - PURPOSE: To investigate the importance of the resistive index (RI) in the
      diagnosis of acute renal rejection, compared with the RI of the twin kidney from
      the same donor, transplanted in two different patients. MATERIAL AND METHODS:
      From January to December 2000, we studied retrospectively 25 pairs (50 patients)
      of renal allografts from the same donor considering the RI obtained with by eco
      color-Doppler ultrasound, daily diuresis and renal function (serum creatinine
      level) in the first six days following surgery. Improvement of diuresis and renal
      function after corticosteroid therapy was considered the gold standard for the
      diagnosis of acute rejection. RESULTS: Medical complications (acute renal
      rejection) in the first six days were occurred in three cases, two in the first
      transplanted kidney as first and one in the second; all three cases showed
      disappearance of the diastolic waveform component. Considering a RI variation
      >0.15 with respect to the initial value, the sensitivity, specificity and
      diagnostic accuracy in the Doppler diagnosis of acute rejection were 100%, 97.1%
      and 97.3% respectively, with a prevalence of 7.8%. There were no statistically
      significant correlations between the RI variation of the renal transplant and the
      twin kidney from the same donor. DISCUSSION AND CONCLUSIONS: Doppler ultrasound
      is an important diagnostic tool in the detection of medical complications in the
      immediate postoperative period and during renal transplant follow-up. RI
      analysis, when studied serially and in the right clinical settings, allows an
      early diagnosis of renal rejection with high sensibility and specificity.

PMID- 11976621
TI  - MR evaluation of anterior cruciate ligament reconstruction with quadriceps
      tendon. Preliminary experience.
AB  - PURPOSE: Anterior cruciate ligament reconstructions are becoming increasingly
      frequent, and MRI has been shown to be the best imaging modality for the non
      invasive assessment of surgical outcome. Use of the quadriceps tendon as a
      biological replacement for injured cruciate ligament is a recent innovation. This
      study evaluated by MRI the results of anterior cruciate reconstruction in 27
      consecutive patients who underwent arthroscopic reconstruction with homologous
      quadriceps tendon. MATERIAL AND METHODS: MRI was carried out on 27 patients who
      had undergone anterior cruciate ligament reconstruction with the middle third of
      the homolateral quadriceps tendon. The examinations were performed on two MRI
      units: a permanent 0.2-Tesla dedicated magnet (Artoscan, Esaote Italy) and whole
      body 1.5-Tesla superconducting magnet (Signa, GE Medical Systems Milwaukee,
      Winsconsin USA). Axial, sagittal and coronal images were acquired with SE, GE and
      STIR fat suppression sequences. The examinations were performed 1, 3, and 6
      months post-operatively in 16 patients, and 1 and 3 post-operatively in 11
      patients. The same arthroscopic surgical technique was employed in all patients,
      with 20 cases of tibial mono-tunnel femoral semi-tunnel, and 7 cases with tibial
      bi-tunnel technique. All patients were assessed by arthrometric and clinical
      tests after surgery. Bioabsorbable interference screws were used for tibial
      fixation in all patients and metallic interference screws were used for femoral
      graft fixation in 8 patients. RESULTS: In all cases MRI correctly visualised the
      tunnel positions, the articular portion and the bone-portion of the graft inside
      the tibial and femoral tunnels. The absence of paramagnetic artefacts in the
      tibia allowed complete visualisation on the axial, sagittal and coronal MRI
      images with optimal spatial and contrast resolutions. In 6 cases, the presence of
      metal residues from the surgical cutter prevented correct evaluation of femoral
      tunnel content. No new graft or articular lesions were found. In 18/27 cases peri
      focal marrow edema around the tibial tunnel had disappeared 3 months after
      surgery. The process of synovial incorporation was judged to be correct in all
      cases. DISCUSSION: The use of anterior cruciate ligament reconstruction with the
      quadriceps tendon is a important innovation given the size of the harvested
      material and the possibility of completely filling the osseous tunnels, without
      interposition of synovial proliferation or fluid collection between tendon and
      bone, as confirmed by MRI. Furthermore, the use of non-metallic screws allows MRI
      evaluation of tunnel content and oedema in the spongy bone around the tunnel. The
      study of the double tibial tunnel requires specific obliqueness in the coronal
      plane scans. CONCLUSIONS: This arthroscopic technique for anterior cruciate
      ligament reconstruction allows thorough MRI evaluation of all portions of the
      transplant, and in particular those coursing within the tibia and femur. The
      absence of bone oedema around the tunnels and synovial proliferation within the
      tunnels may be predictive of faster healing and complete bone incorporation of
      the grafts.

PMID- 11976622
TI  - Analysis of radioactive pollution in the Gulf of Palermo.
AB  - PURPOSE: Sea water represents more than three quarters of the whole world. The
      radioactive fall out caused by nuclear experiments, radioactive drosses from
      nuclear power plants and other pollution sources, are able to contaminate the
      world ecosystems, and especially the sea water. The aim of this work is the
      evaluation of a possible radioactive pollution in the Gulf of Palermo. MATERIAL
      AND METHODS: The Gulf of Palermo was divided into 5 homogeneous hydrological
      parts, in which fish and water were collected. The dosage of 131I e del 137Cs was
      mainly assessed because they have a long half-life and their presence in the
      water can be due to nuclear accidents but also to a wrong removal of the waste
      materials of nuclear medicine procedures; the other radioisotopes assessed
      (144Ce, 106Rh, 140La) are due only to nuclear fall-out. Gamma spectrometry
      technique was used for the evaluation of the radioisotopes' concentration after
      an adequate treatment of the samples. RESULTS AND CONCLUSIONS: The concentration
      of the examined radionuclides was below the instrumental capability apart from
      the 137Cs, whose dose was increased, and can be due to nuclear accidents and
      explosions. The radionuclide levels detected do not determine a higher risk than
      normal for the population's health even regard the eatablity of ittical species.

PMID- 11976620
TI  - Peripheral quantitative Computed Tomography (PQCT) in the evaluation of bone
      geometry, biomechanics and mineral density in postmenopausal women.
AB  - AIM: Non-invasive assessment of bone geometry, biomechanics, and mineral content
      in postmenopausal women by peripheral quantitative Computed Tomography (pQCT).
      MATERIAL AND METHODS: Total, trabecular and cortical mineral density (totBMD,
      cortBMD, trabBMD), and the geometrical (total area, trabecular area, cortical
      area) and biomechanical properties of bone (strength-strain index, cortical
      thickness) were assessed in 93 consecutive post-menopausal women (mean age: 63+/
      7 yrs; age at menopause: 49+/-6 yrs; years since menopause: 14+/-9 yrs) by pQCT
      at the ultradistal radius of non-dominant forearm. RESULTS: Compared with 50
      healthy women at peak of bone mass, volumetric total, trabecular and cortical
      bone densities were significantly reduced in postmenopausal subjects (TotBMD:
      318+/-106 mg/cm3 vs ctr 442+/-100, -28%, p<0.001; TrabBMD: 117+/-59 mg/cm3 vs
      ctr: 203+/-47, -42%, p<0.001; CorBMD: 764+/-159 mg/cm3 vs 921+/-111, -17%,
      p<0.001). The bone loss was greater in trabecular bone. Cortical area (0.7+/-0,1
      cm2 vs ctr: 0.8+/-0.1, -12.5%, p<0.001), cortical thickness (0.151+/-0.02 cm vs
      ctr: 0.169+/-0.03, -11%, p<0.001), and strength-strain index (686+/-207 mm3 vs
      ctr: 883+/-165, -22%, p<0.001) were significantly lower in post-menopausal women
      in comparison with the controls. Years since menopause and age showed a
      significant negative correlation with bone mineral densities and biomechanical
      parameters. CONCLUSIONS: In post-menopausal women pQCT showed: 1) osteopoenia in
      all bone compartments, greater at the trabecular level, related to age and years
      since menopause; 2) reduced cortical density and cortical thickness, consistent
      with a reduced ability of bone to absorb loading forces; 3) reduced strength
      strain index, indicative of inability to adapt to mechanical use and augmented
      risk for fracture. We conclude that pQCT is a valuable tool for measuring the
      true volumetric mineral density and the geometrical and biomechanical indexes of
      bone, which could be proposed in current clinical practice for the assessment of
      osteoporosis.

PMID- 11976623
TI  - Complex cerebral malformation including Dandy-Walker in a newborn with trisomy 9
      mosaicism.

PMID- 11976624
TI  - Thoracic schwannoma in neurofibromatosis type I.A case report.

PMID- 11976625
TI  - Siphoning effect and steal phenomenon combined to focal hepatic lesions on spiral
      CT. Four cases report.

PMID- 11976626
TI  - Treatment of anastomotic iliac pseudoaneurysm.

PMID- 11976627
TI  - Primary renal non-Hodgkin's lymphoma with inferior vena cava involvement: report
      of one case in HIV-infected patient.

PMID- 11976628
TI  - Mucous cysts of bone communicating with the joint cavity.

PMID- 11976629
TI  - Hypercalcemia.

PMID- 11976631
TI  - Getting into good company.

PMID- 11976633
TI  - France sleepwalks into chaos.

PMID- 11976632
TI  - Maintaining the climate consensus.

PMID- 11976634
TI  - Allegations of rushed proposals mar disease fund's first awards.

PMID- 11976640
TI  - Melting ice triggers Himalayan flood warning.

PMID- 11976643
TI  - Chemistry caught in crisis catalysed by student apathy.

PMID- 11976644
TI  - South African leader relents in storm over HIV drugs for women.

PMID- 11976645
TI  - Cell biology: will the real Golgi please stand up.

PMID- 11976646
TI  - Social insects: the police state.

PMID- 11976647
TI  - 'Practical autonomy' entitles some animals to rights.

PMID- 11976648
TI  - Cancer centre didn't shoot the messenger.

PMID- 11976649
TI  - A theory can be falsified or tested. Faith cannot.

PMID- 11976659
TI  - Global enzymes: sphere of influence.

PMID- 11976660
TI  - Astronomy: the cosmic accelerator.

PMID- 11976662
TI  - Semiconductors: an eye for impurity.

PMID- 11976661
TI  - Mammalian evolution: upwards and onwards.

PMID- 11976663
TI  - Plant biology: on guard.

PMID- 11976664
TI  - Agriculture: champagne surprise.

PMID- 11976666
TI  - Relativity: testing times in space.

PMID- 11976669
TI  - Obituary: Cesar Milstein (1927-2002).

PMID- 11976667
TI  - Developmental biology: an arresting activity.

PMID- 11976670
TI  - Coprophagy: an unusual source of essential carotenoids.
AB  - The rare Egyptian vulture (Neophron percnopterus) stands out among the Old World
      vultures (Family Accipitridae) because of its brightly ornamented head, which is
      coloured yellow by carotenoid pigments, and its practice of feeding on faeces.
      Here we show that Egyptian vultures obtain these pigments from the excrement of
      ungulates. To our knowledge, this is the first demonstration that faeces can be
      used as a source of carotenoids by a vertebrate.

PMID- 11976672
TI  - Spintronics: spin accumulation in mesoscopic systems.
AB  - In spintronics, in which use is made of the spin degree of freedom of the
      electron, issues concerning electrical spin injection and detection of electron
      spin diffusion are fundamentally important. Jedema et al. describe a magneto
      resistance study in which they claim to have observed spin accumulation in a
      mesoscopic copper wire, but their one-dimensional model ignores two-dimensional
      spin-diffusion effects, which casts doubt on their analysis. A two-dimensional
      vector formalism of spin transport is called for to model spin-injection
      experiments, and the identification of spurious background resistance effects is
      crucial.

PMID- 11976671
TI  - Biodiversity: invasions by marine life on plastic debris.
AB  - Colonization by alien species poses one of the greatest threats to global
      biodiversity. Here I investigate the colonization by marine organisms of drift
      debris deposited on the shores of 30 remote islands from the Arctic to the
      Antarctic (across all oceans) and find that human litter more than doubles the
      rafting opportunities for biota, particularly at high latitudes. Although the
      poles may be protected from invasion by freezing sea surface temperatures, these
      may be under threat as the fastest-warming areas anywhere are at these latitudes.

PMID- 11976673
TI  - Spintronics (Communication arising): Spin accumulation in mesoscopic systems.
AB  - Johnson suggests that our results are not due to spin transport but rather are
      caused by spurious effects, in particular the anisotropic magneto resistance of
      the ferromagnetic contacts. However, our experiment was designed explicitly to
      eliminate any magneto-resistance effects that might arise from the ferromagnetic
      contacts.

PMID- 11976674
TI  - Insights into phase transition kinetics from colloid science.
AB  - Colloids display intriguing transitions between gas, liquid, solid and liquid
      crystalline phases. Such phase transitions are ubiquitous in nature and have been
      studied for decades. However, the predictions of phase diagrams are not always
      realized; systems often become undercooled, supersaturated, or trapped in gel
      like states. In many cases the end products strongly depend on the starting
      position in the phase diagram and discrepancies between predictions and actual
      observations are due to the intricacies of the dynamics of phase transitions.
      Colloid science aims to understand the underlying mechanisms of these
      transitions. Important advances have been made, for example, with new imaging
      techniques that allow direct observation of individual colloidal particles
      undergoing phase transitions, revealing some of the secrets of the complex
      pathways involved.

PMID- 11976677
TI  - Atomic-scale imaging of individual dopant atoms and clusters in highly n-type
      bulk Si.
AB  - As silicon-based transistors in integrated circuits grow smaller, the
      concentration of charge carriers generated by the introduction of impurity dopant
      atoms must steadily increase. Current technology, however, is rapidly approaching
      the limit at which introducing additional dopant atoms ceases to generate
      additional charge carriers because the dopants form electrically inactive
      clusters. Using annular dark-field scanning transmission electron microscopy, we
      report the direct, atomic-resolution observation of individual antimony (Sb)
      dopant atoms in crystalline Si, and identify the Sb clusters responsible for the
      saturation of charge carriers. The size, structure, and distribution of these
      clusters are determined with a Sb-atom detection efficiency of almost 100%.
      Although single heavy atoms on surfaces or supporting films have been visualized
      previously, our technique permits the imaging of individual dopants and clusters
      as they exist within actual devices.

PMID- 11976678
TI  - Molecular segregation observed in a concentrated alcohol-water solution.
AB  - When a simple alcohol such as methanol or ethanol is mixed with water, the
      entropy of the system increases far less than expected for an ideal solution of
      randomly mixed molecules. This well-known effect has been attributed to
      hydrophobic headgroups creating ice-like or clathrate-like structures in the
      surrounding water, although experimental support for this hypothesis is scarce.
      In fact, an increasing amount of experimental and theoretical work suggests that
      the hydrophobic headgroups of alcohol molecules in aqueous solution cluster
      together. However, a consistent description of the details of this self
      association is lacking. Here we use neutron diffraction with isotope substitution
      to probe the molecular-scale structure of a concentrated alcohol water mixture
      (7:3 molar ratio). Our data indicate that most of the water molecules exist as
      small hydrogen-bonded strings and clusters in a 'fluid' of close-packed methyl
      groups, with water clusters bridging neighbouring methanol hydroxyl groups
      through hydrogen bonding. This behaviour suggests that the anomalous
      thermodynamics of water alcohol systems arises from incomplete mixing at the
      molecular level and from retention of remnants of the three-dimensional hydrogen
      bonded network structure of bulk water.

PMID- 11976675
TI  - The earliest known eutherian mammal.
AB  - The skeleton of a eutherian (placental) mammal has been discovered from the Lower
      Cretaceous Yixian Formation of northeastern China. We estimate its age to be
      about 125 million years (Myr), extending the date of the oldest eutherian records
      with skull and skeleton by about 40 50 Myr. Our analyses place the new fossil at
      the root of the eutherian tree and among the four other known Early Cretaceous
      eutherians, and suggest an earlier and greater diversification of stem eutherians
      that occurred well before the molecular estimate for the diversification of
      extant placental superorders (104 64 Myr). The new eutherian has limb and foot
      features that are known only from scansorial (climbing) and arboreal (tree
      living) extant mammals, in contrast to the terrestrial or cursorial (running)
      features of other Cretaceous eutherians. This suggests that the earliest
      eutherian lineages developed different locomotory adaptations, facilitating their
      spread to diverse niches in the Cretaceous.

PMID- 11976676
TI  - The acceleration of cosmic-ray protons in the supernova remnant RX J1713.7-3946.
AB  - Protons with energies up to approximately 10(15) eV are the main component of
      cosmic rays, but evidence for the specific locations where they could have been
      accelerated to these energies has been lacking. Electrons are known to be
      accelerated to cosmic-ray energies in supernova remnants, and the shock waves
      associated with such remnants, when they hit the surrounding interstellar medium,
      could also provide the energy to accelerate protons. The signature of such a
      process would be the decay of pions (pi(0)), which are generated when the protons
      collide with atoms and molecules in an interstellar cloud: pion decay results in
      gamma-rays with a particular spectral-energy distribution. Here we report the
      observation of cascade showers of optical photons resulting from gamma-rays at
      energies of approximately 10(12) eV hitting Earth's upper atmosphere, in the
      direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match
      to that predicted by pion decay, and cannot be explained by other mechanisms.

PMID- 11976679
TI  - Rapid freshening of the deep North Atlantic Ocean over the past four decades.
AB  - The overflow and descent of cold, dense water from the sills of the Denmark
      Strait and the Faroe Shetland channel into the North Atlantic Ocean is the
      principal means of ventilating the deep oceans, and is therefore a key element of
      the global thermohaline circulation. Most computer simulations of the ocean
      system in a climate with increasing atmospheric greenhouse-gas concentrations
      predict a weakening thermohaline circulation in the North Atlantic as the
      subpolar seas become fresher and warmer, and it is assumed that this signal will
      be transferred to the deep ocean by the two overflows. From observations it has
      not been possible to detect whether the ocean's overturning circulation is
      changing, but recent evidence suggests that the transport over the sills may be
      slackening. Here we show, through the analysis of long hydrographic records, that
      the system of overflow and entrainment that ventilates the deep Atlantic has
      steadily changed over the past four decades. We find that these changes have
      already led to sustained and widespread freshening of the deep ocean.

PMID- 11976680
TI  - Ecosystem consequences of species richness and composition in pond food webs.
AB  - Resolving current concerns about the role of biodiversity on ecosystems calls for
      understanding the separate roles of changes in species numbers and of
      composition. Recent work shows that primary productivity often, but not always,
      saturates with species richness within single trophic levels. However, any
      interpretation of such patterns must consider that variation in biodiversity is
      necessarily associated with changes in species composition (identity), and that
      changes in biodiversity often occur across multiple trophic levels. Here we
      present results from a mesocosm experiment in which we independently manipulated
      species richness and species composition across multiple trophic levels in pond
      food webs. In contrast to previous studies that focused on single trophic levels,
      we found that productivity is either idiosyncratic or increases with respect to
      species richness, and that richness influences trophic structure. However, the
      composition of species within richness levels can have equally or more marked
      effects on ecosystems than average effects of richness per se. Indirect evidence
      suggests that richness and associated changes in species composition affect
      ecosystem attributes through indirect effects and trophic interactions among
      species, features that are highly characteristic of natural, complex ecosystems.

PMID- 11976681
TI  - Low host specificity of herbivorous insects in a tropical forest.
AB  - Two decades of research have not established whether tropical insect herbivores
      are dominated by specialists or generalists. This impedes our understanding of
      species coexistence in diverse rainforest communities. Host specificity and
      species richness of tropical insects are also key parameters in mapping global
      patterns of biodiversity. Here we analyse data for over 900 herbivorous species
      feeding on 51 plant species in New Guinea and show that most herbivorous species
      feed on several closely related plant species. Because species-rich genera are
      dominant in tropical floras, monophagous herbivores are probably rare in tropical
      forests. Furthermore, even between phylogenetically distant hosts, herbivore
      communities typically shared a third of their species. These results do not
      support the classical view that the coexistence of herbivorous species in the
      tropics is a consequence of finely divided plant resources; non-equilibrium
      models of tropical diversity should instead be considered. Low host specificity
      of tropical herbivores reduces global estimates of arthropod diversity from 31
      million (ref. 1) to 4 6 million species. This finding agrees with estimates based
      on taxonomic collections, reconciling an order of magnitude discrepancy between
      extrapolations of global diversity based on ecological samples of tropical
      communities with those based on sampling regional faunas.

PMID- 11976682
TI  - Developmental constraints versus flexibility in morphological evolution.
AB  - Evolutionary developmental biology has encouraged a change of research emphasis
      from the sorting of phenotypic variation by natural selection to the production
      of that variation through development. Some morphologies are more readily
      generated than others, and developmental mechanisms can limit or channel
      evolutionary change. Such biases determine how readily populations are able to
      respond to selection, and have been postulated to explain stasis in morphological
      evolution and unexplored morphologies. There has been much discussion about
      evolutionary constraints but empirical data testing them directly are sparse. The
      spectacular diversity in butterfly wing patterns is suggestive of how little
      constrained morphological evolution can be. However, for wing patterns involving
      serial repeats of the same element, developmental properties suggest that some
      directions of evolutionary change might be restricted. Here we show that despite
      the developmental coupling between different eyespots in the butterfly Bicyclus
      anynana, there is great potential for independent changes. This flexibility is
      consistent with the diversity of wing patterns across species and argues for a
      dominant role of natural selection, rather than internal constraints, in shaping
      existing variation.

PMID- 11976683
TI  - Association of dwarfism and floral induction with a grape 'green revolution'
      mutation.
AB  - The transition from vegetative to reproductive growth is an essential process in
      the life cycle of plants. Plant floral induction pathways respond to both
      environmental and endogenous cues and much has been learnt about these genetic
      pathways by studying mutants of Arabidopsis. Gibberellins (GAs) are plant growth
      regulators important in many aspects of plant growth and in Arabidopsis they
      promote flowering. Here we provide genetic evidence that GAs inhibit flowering in
      grapevine. A grapevine dwarf mutant derived from the L1 cell layer of the
      champagne cultivar Pinot Meunier produces inflorescences along the length of the
      shoot where tendrils are normally formed. The mutated gene associated with the
      phenotype is a homologue of the wheat 'green revolution' gene Reduced height-1
      (ref. 6) and the Arabidopsis gene GA insensitive (GAI). The conversion of
      tendrils to inflorescences in the mutant demonstrates that the grapevine tendril
      is a modified inflorescence inhibited from completing floral development by GAs.

PMID- 11976684
TI  - Emi1 is required for cytostatic factor arrest in vertebrate eggs.
AB  - Vertebrate eggs are arrested at metaphase of meiosis II with stable cyclin B and
      high cyclin B/Cdc2 kinase activity. The ability of the anaphase-promoting
      complex/cyclosome (APC), an E3 ubiquitin ligase, to trigger cyclin B destruction
      and metaphase exit is blocked in eggs by the activity of cytostatic factor (CSF)
      (reviewed in ref. 1). CSF was defined as an activity in mature oocytes that
      caused mitotic arrest when injected into dividing embryos. Fertilization causes a
      transient increase in cytoplasmic calcium concentration leading to CSF
      inactivation, APC activation, cyclin B destruction and mitotic exit. The APC
      activator Cdc20 is required for APC activation after fertilization. We show here
      that the APC(cdc20) inhibitor Emi1 (ref. 6) is necessary and sufficient to
      inhibit the APC and to prevent mitotic exit in CSF-arrested eggs. CSF extracts
      immunodepleted of Emi1 degrade cyclin B, and exit from mitosis prematurely in the
      absence of calcium. Addition of Emi1 to these Emi1-depleted extracts blocks
      premature inactivation of the CSF-arrested state. Emi1 is required to arrest
      unfertilized eggs at metaphase of meiosis II and seems to be the long-sought
      mediator of CSF activity.

PMID- 11976686
TI  - Protein kinase Cdelta controls self-antigen-induced B-cell tolerance.
AB  - Interaction of a B cell expressing self-specific B-cell antigen receptor (BCR)
      with an auto-antigen results in either clonal deletion or functional
      inactivation. Both of these processes lead to B-cell tolerance and are essential
      for the prevention of auto-immune diseases. Whereas clonal deletion results in
      the death of developing autoreactive B cells, functional inactivation of self
      reactive B lymphocytes leads to complex changes in the phenotype of peripheral B
      cells, described collectively as anergy. Here we demonstrate that deficiency in
      protein kinase Cdelta (PKC-delta) prevents B-cell tolerance, and allows
      maturation and terminal differentiation of self-reactive B cells in the presence
      of the tolerizing antigen. The importance of PKC-delta in B-cell tolerance is
      further underscored by the appearance of autoreactive anti-DNA and anti-nuclear
      antibodies in the serum of PKC-delta-deficient mice. As deficiency of PKC-delta
      does not affect BCR-mediated B-cell activation in vitro and in vivo, our data
      suggest a selective and essential role of PKC-delta in tolerogenic, but not
      immunogenic, B-cell responses.

PMID- 11976685
TI  - Dominant role of the niche in melanocyte stem-cell fate determination.
AB  - Stem cells which have the capacity to self-renew and generate differentiated
      progeny are thought to be maintained in a specific environment known as a niche.
      The localization of the niche, however, remains largely obscure for most stem
      cell systems. Melanocytes (pigment cells) in hair follicles proliferate and
      differentiate closely coupled to the hair regeneration cycle. Here we report that
      stem cells of the melanocyte lineage can be identified, using Dct-lacZ transgenic
      mice, in the lower permanent portion of mouse hair follicles throughout the hair
      cycle. It is only the population in this region that fulfils the criteria for
      stem cells, being immature, slow cycling, self-maintaining and fully competent in
      regenerating progeny on activation at early anagen (the growing phase of hair
      follicles). Induction of the re-pigmentation process in K14-steel factor
      transgenic mice demonstrates that a portion of amplifying stem-cell progeny can
      migrate out from the niche and retain sufficient self-renewing capability to
      function as stem cells after repopulation into vacant niches. Our data indicate
      that the niche has a dominant role in the fate determination of melanocyte stem
      cell progeny.

PMID- 11976688
TI  - AP-1 functions upstream of CREB to control synaptic plasticity in Drosophila.
AB  - Activity-regulated gene expression mediates many aspects of neural plasticity,
      including long-term memory. In the prevailing view, patterned synaptic activity
      causes kinase-mediated activation of the transcription factor cyclic AMP response
      element-binding protein, CREB. Together with appropriate cofactors, CREB then
      transcriptionally induces a group of 'immediate early' transcription factors and,
      eventually, effector proteins that establish or consolidate synaptic change.
      Here, using a Drosophila model synapse, we analyse cellular functions and
      regulation of the best known immediate early transcription factor, AP-1; a
      heterodimer of the basic leucine zipper proteins Fos and Jun. We observe that AP
      1 positively regulates both synaptic strength and synapse number, thus showing a
      greater range of influence than CREB. Observations from genetic epistasis and RNA
      quantification experiments indicate that AP-1 acts upstream of CREB, regulates
      levels of CREB messenger RNA, and functions at the top of the hierarchy of
      transcription factors known to regulate long-term plasticity. A Jun-kinase
      signalling module provides a CREB-independent route for neuronal AP-1 activation;
      thus, CREB regulation of AP-1 expression may, in some neurons, constitute a
      positive feedback loop rather than the primary step in AP-1 activation.

PMID- 11976687
TI  - Increased proliferation of B cells and auto-immunity in mice lacking protein
      kinase Cdelta.
AB  - Protein kinase C (PKC), which comprises 11 closely related isoforms, has been
      implicated in a wide variety of cellular processes, such as growth,
      differentiation, secretion, apoptosis and tumour development. Among the PKC
      isotypes, PKC-delta is unique in that its overexpression results in inhibition of
      cell growth. Here we show that mice that lack PKC-delta exhibit expansion of the
      B-lymphocyte population with the formation of numerous germinal centres in the
      absence of stimulation. The rate of proliferation in response to stimulation was
      greater for B cells from PKC-delta-deficient mice than for those from wild-type
      mice. Adoptive transfer experiments suggested that the hyperproliferation
      phenotype is B-cell autonomous. Production of interleukin-6 was markedly
      increased in B cells of PKC-delta-null mice as a result of an increase in the DNA
      binding activity of NF-IL6. Furthermore, the PKC-delta-deficient mice contain
      circulating autoreactive antibodies and display immune-complex-type
      glomerulonephritis, as well as lymphocyte infiltration in many organs. These
      results suggest that PKC-delta has an indispensable function in negative
      regulation of B-cell proliferation, and is particularly important for the
      establishment of B-cell tolerance.

PMID- 11976689
TI  - Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4.
AB  - Hearing depends on a high K(+) concentration bathing the apical membranes of
      sensory hair cells. K(+) that has entered hair cells through apical
      mechanosensitive channels is transported to the stria vascularis for re-secretion
      into the scala media(). K(+) probably exits outer hair cells by KCNQ4 K(+)
      channels(), and is then transported by means of a gap junction system connecting
      supporting Deiters' cells and fibrocytes() back to the stria vascularis. We show
      here that mice lacking the K(+)/Cl(-) (K-Cl) co-transporter Kcc4 (coded for by
      Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning
      of hearing. In the mature organ of Corti, Kcc4 is restricted to supporting cells
      of outer and inner hair cells. Our data suggest that Kcc4 is important for K(+)
      recycling() by siphoning K(+) ions after their exit from outer hair cells into
      supporting Deiters' cells, where K(+) enters the gap junction pathway. Similar to
      some human genetic syndromes(), deafness in Kcc4-deficient mice is associated
      with renal tubular acidosis. It probably results from an impairment of Cl(-)
      recycling across the basolateral membrane of acid-secreting alpha-intercalated
      cells of the distal nephron.

PMID- 11976690
TI  - Structural determinants for GoLoco-induced inhibition of nucleotide release by
      Galpha subunits.
AB  - Heterotrimeric G-proteins bind to cell-surface receptors and are integral in
      transmission of signals from outside the cell. Upon activation of the Galpha
      subunit by binding of GTP, the Galpha and Gbetagamma subunits dissociate and
      interact with effector proteins for signal transduction. Regulatory proteins with
      the 19-amino-acid GoLoco motif can bind to Galpha subunits and maintain G-protein
      subunit dissociation in the absence of Galpha activation. Here we describe the
      structural determinants of GoLoco activity as revealed by the crystal structure
      of Galpha(i1) GDP bound to the GoLoco region of the 'regulator of G-protein
      signalling' protein RGS14. Key contacts are described between the GoLoco motif
      and Galpha protein, including the extension of GoLoco's highly conserved Asp/Glu
      Gln-Arg triad into the nucleotide-binding pocket of Galpha to make direct contact
      with the GDP alpha- and beta-phosphates. The structural organization of the
      GoLoco Galpha(i1) complex, when combined with supporting data from domain
      swapping experiments, suggests that the Galpha all-helical domain and GoLoco
      region carboxy-terminal residues control the specificity of GoLoco Galpha
      interactions.

PMID- 11976691
TI  - Microarray technology: an array of opportunities.

PMID- 11976695
TI  - Brave New World revisited.

PMID- 11976696
TI  - What a privilege to reside at the synapse: NMDA receptor signaling to CREB.

PMID- 11976699
TI  - Making order from chaos: the misguided frontal lobe.

PMID- 11976698
TI  - Neural stem cells: form and function.

PMID- 11976697
TI  - Rethinking the taxonomy of visual neurons.

PMID- 11976702
TI  - Cyclic AMP-dependent protein kinase phosphorylation facilitates GABA(B) receptor
      effector coupling.
AB  - GABA (gamma-aminobutyric acid)(B) receptors are heterodimeric G protein-coupled
      receptors that mediate slow synaptic inhibition in the central nervous system.
      Here we show that the functional coupling of GABA(B)R1/GABA(B)R2 receptors to
      inwardly rectifying K(+) channels rapidly desensitizes. This effect is alleviated
      after direct phosphorylation of a single serine residue (Ser892) in the
      cytoplasmic tail of GABA(B)R2 by cyclic AMP (cAMP)-dependent protein kinase
      (PKA). Basal phosphorylation of this residue is evident in rat brain membranes
      and in cultured neurons. Phosphorylation of Ser892 is modulated positively by
      pathways that elevate cAMP concentration, such as those involving forskolin and
      beta-adrenergic receptors. GABA(B) receptor agonists reduce receptor
      phosphorylation, which is consistent with PKA functioning in the control of
      GABA(B)-activated currents. Mechanistically, phosphorylation of Ser892
      specifically enhances the membrane stability of GABA(B) receptors. We conclude
      that signaling pathways that activate PKA may have profound effects on GABA(B)
      receptor-mediated synaptic inhibition. These results also challenge the accepted
      view that phosphorylation is a universal negative modulator of G protein-coupled
      receptors.

PMID- 11976703
TI  - A protein kinase A-dependent molecular switch in synapsins regulates neurite
      outgrowth.
AB  - Cyclic AMP (cAMP) promotes neurite outgrowth in a variety of neuronal cell lines
      through the activation of protein kinase A (PKA). We show here, using both
      Xenopus laevis embryonic neuronal culture and intact X. laevis embryos, that the
      nerve growth-promoting action of cAMP/PKA is mediated in part by the
      phosphorylation of synapsins at a single amino acid residue. Expression of a
      mutated form of synapsin that prevents phosphorylation at this site, or
      introduction of phospho-specific antibodies directed against this site, decreased
      basal and dibutyryl cAMP-stimulated neurite outgrowth. Expression of a mutation
      mimicking constitutive phosphorylation at this site increased neurite outgrowth,
      both under basal conditions and in the presence of a PKA inhibitor. These results
      provide a potential molecular approach for stimulating neuron regeneration, after
      injury and in neurodegenerative diseases.

PMID- 11976704
TI  - Postsynaptic endocannabinoid release is critical to long-term depression in the
      striatum.
AB  - The striatum functions critically in movement control and habit formation. The
      development and function of cortical input to the striatum are thought to be
      regulated by activity-dependent plasticity of corticostriatal glutamatergic
      synapses. Here we show that the induction of a form of striatal synaptic
      plasticity, long-term depression (LTD), is dependent on activation of the CB1
      cannabinoid receptor. LTD was facilitated by blocking cellular endocannabinoid
      uptake, and postsynaptic loading of anandamide (AEA) produced presynaptic
      depression. The endocannabinoid necessary for striatal LTD is thus likely to be
      released postsynaptically as a retrograde messenger. These findings demonstrate a
      new role for endocannabinoids in the induction of long-term synaptic plasticity
      in a circuit necessary for habit formation and motor control.

PMID- 11976705
TI  - Critical role of the hippocampus in memory for sequences of events.
AB  - Recent models of hippocampal function emphasize the potential role of this brain
      structure in encoding and retrieving sequences of events that compose episodic
      memories. Here we show that hippocampal lesions produce a severe and selective
      impairment in the capacity of rats to remember the sequential ordering of a
      series of odors, despite an intact capacity to recognize odors that recently
      occurred. These findings support the hypothesis that hippocampal networks mediate
      associations between sequential events that constitute elements of an episodic
      memory.

PMID- 11976710
TI  - Walking before running.

PMID- 11976706
TI  - Limits to the temporal fidelity of cortical spike rate signals.
AB  - The cerebral cortex processes information primarily through changes in the spike
      rates of neurons within local ensembles. To evaluate how reliably the average
      spike rate of a group of cortical neurons can represent a time-varying signal, we
      simulated an ensemble with realistic spike discharge behavior. We found that weak
      interneuronal correlation, or synchrony, allows the variability in spike rates of
      individual neurons to compromise the ensemble representation of time-varying
      signals. Brief cycles of sinusoidal modulation at frequencies above 115 Hz could
      not be represented by an ensemble of hundreds of neurons whose interneuronal
      correlation mimics that of the visual cortex. The spike variability and
      correlation assumed in our simulations are likely to apply to many areas of
      cortex and therefore may constrain the fidelity of neural computations underlying
      higher brain function.

PMID- 11976714
TI  - A season for midwinter immunology.

PMID- 11976711
TI  - Autoantibodies to GPI and creatine kinase in RA.

PMID- 11976712
TI  - Few human autoimmune sera detect GPI.

PMID- 11976717
TI  - Lipid presentation by CD1: the short and the long lipid story.

PMID- 11976715
TI  - Neuropilin-1: another neuronal molecule in the "immunological synapse".

PMID- 11976716
TI  - A new spin on an unusual tail.

PMID- 11976720
TI  - Structural mechanisms of costimulation.
AB  - Recent studies have highlighted the structural requirements for T cell
      costimulation and have revealed unusual modes of dimerization for the cytolytic T
      lymphocyte-associated antigen 4 (CTLA-4) costimulatory receptor and its B7
      ligands. These distinctive quaternary structures potentially endow both receptor
      and ligand with bivalent binding properties, which suggests a number of
      mechanistic features relevant to signaling. These include the potential to form a
      highly ordered, alternating network of CTLA-4 and B7 homodimers that may
      represent the organization of these molecules and their associated signaling
      partners within the immunological synapse. Primary sequence and structural
      considerations suggest that some aspects of the organizational and mechanistic
      features associated with the CTLA-4-B7 complexes may extend to other members of
      the costimulatory receptor-ligand family. An examination of the signaling
      mechanisms within the costimulatory receptor-ligand family provides an excellent
      framework to consider the general principles that are relevant to cell surface
      receptor-mediated signaling events.

PMID- 11976718
TI  - A role for Toll in autoimmunity.

PMID- 11976722
TI  - Putting the beta-breaks on membrane protein misfolding.

PMID- 11976724
TI  - Towards an understanding of amyloidogenesis.

PMID- 11976723
TI  - Chips off the old block.

PMID- 11976725
TI  - Picture story. Locked but not loaded.

PMID- 11976726
TI  - SH3-dependent stimulation of Src-family kinase autophosphorylation without tail
      release from the SH2 domain in vivo.
AB  - Src family protein-tyrosine kinase activity is suppressed by two intramolecular
      interactions. These involve binding of the SH2 domain to the phosphorylated C
      terminal tail and association of the SH3 domain with a polyproline type II helix
      formed by the SH2-kinase linker. Here we show that SH3-dependent activation of
      the Src family member Hck by HIV-1 Nef binding or by SH2-kinase linker mutation
      does not affect tail tyrosine phosphorylation in fibroblasts. Surprisingly,
      replacement of the wild type Hck tail with a high-affinity SH2 domain-binding
      sequence did not affect Hck activation or downstream signaling by these SH3
      dependent mechanisms, suggesting that activation through SH3 occurs without SH2
      tail dissociation. These results identify SH3-linker interaction as an
      independent mode of Hck kinase regulation in vivo and suggest that different
      mechanisms of Src kinase activation may generate distinct output signals because
      of differences in SH2 or SH3 domain accessibility.

PMID- 11976727
TI  - Friedrich Cameron Luft turns 60: bridging the New and the Old World.

PMID- 11976729
TI  - The genetic background of autoimmune polyendocrinopathy-candidiasis-ectodermal
      dystrophy and its autoimmune disease components.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare
      autosomal recessive disorder characterized by an immune-mediated destruction of
      endocrine tissues, chronic candidiasis, and additional ectodermal disorders. In
      contrast to many other autoimmune diseases, APECED is associated with mutations
      of a single gene, designated autoimmune regulator (AIRE). To date, 45 different
      mutations of the AIRE gene have been identified and are distributed throughout
      the entire coding region. Several of the AIRE mutations predict the transcription
      and translation of a truncated protein, which may be nonfunctional. In contrast
      to the genetic background of APECED, in all of the autoimmune conditions
      typically associated with APECED the conclusive role of a single genetic locus
      capable of providing insight into the etiology of the disease has not been
      identified. Here we provide an overview of the current clinical and genetic
      features of APECED in comparison to the genetic background of the frequently
      associated disease components of APECED.

PMID- 11976731
TI  - Targeted chemotherapy: chronic myelogenous leukemia as a model.
AB  - Many of the therapeutic agents used for cancer chemotherapy today are based on
      decades-old agents which are highly cytotoxic but are nonselective for cancer
      cells. The hallmark of chronic myelogenous leukemia (CML) is the Philadelphia
      chromosome translocation t(9;22), which results in the bcr-abl fusion gene. As an
      alteration that is nearly universal in CML cells, bcr-abl presents a therapeutic
      target that is unique to the pathological cells in CML patients. Advances in the
      understanding of the molecular mechanisms which sustain leukemic cells in CML
      have enabled the development of selective therapies for this disease. We review
      here the molecular pathogenesis and current treatment of CML. We also discuss the
      development of imatinib mesylate, a selective inhibitor of Bcr-Abl which has
      shown promise in clinical trials with CML. This recent advance in CML therapy
      represents a novel approach to rational design and development of new anticancer
      drugs.

PMID- 11976730
TI  - Adoptive cancer immunotherapy: discovering the best targets.
AB  - Numerous animal and clinical studies have shown that injection of T lymphocytes
      from a major histocompatibility complex matched donor can cure subjects with
      chemotherapy-resistant hematological malignancies. This graft-versus-tumor
      effect, which represents the most conclusive evidence that the immune system can
      cure cancer in humans, is mediated primarily if not exclusively by T cells
      specific for host minor histocompatibility antigens. Since minor
      histocompatibility antigens are present on all tissues and organs, injection of
      unselected donor T cells also causes graft vs. host disease, which drastically
      limits the use and benefits of this treatment. Recent studies in mice have shown
      that adoptive transfer of primed T cells targeted to a single major
      histocompatibility complex class I restricted immunodominant minor
      histocompatibility antigen can eradicate leukemia cells without causing any
      toxicity to the host. We present the promises and caveats of this and other new
      approaches for adoptive T cell immunotherapy of cancer.

PMID- 11976732
TI  - Antiviral activity of artesunate towards wild-type, recombinant, and ganciclovir
      resistant human cytomegaloviruses.
AB  - Antiviral therapy of primary and recurrent infections with human cytomegalovirus
      is reserved for severe manifestations and faces several limitations. Presently
      candidates for novel drugs with lower adverse side effects and a minimized
      frequency of resistance formation are under investigation. Here we demonstrate
      that artesunate, an antimalaria drug with highly valuable pharmacological
      properties, possesses antiviral activity. A concentration-dependent inhibition of
      the replication of human cytomegaloviruses with wild-type phenotype was
      demonstrated in several cell lines. Inhibition was quantified using recombinant
      green fluorescent protein expressing virus variants. The IC50 values were in the
      same range for ganciclovir-sensitive and ganciclovir-resistant human
      cytomegalovirus, as calculated with 5.8+/-0.4 microM and 6.9+/-0.2 microM,
      respectively. This indicated a strong antiviral potential and a lack of cross
      resistance. The optimal antiviral concentrations of artesunate were separable
      from those inducing cytotoxicity. In addition, the replication of viruses from
      three genera was seen to be artesunate-sensitive to varying degrees. This
      suggests a mechanism linked to cellular activation pathways. Both the protein
      levels and the DNA binding activity of the two virus-induced cellular
      transcription factors Sp1 and NF-kappaB were found to be markedly reduced in the
      presence of artesunate. We also analyzed the cellular signaling kinase
      phosphoinositide 3-kinase, required for the activation of factors such as Sp1 and
      NF-kappaB in infected fibroblasts. The phosphorylation of two downstream
      effectors of phosphoinositide 3-kinase, Akt and p70S6K, was markedly inhibited in
      the presence of artesunate. Thus, artesunate possesses attractive antiviral
      characteristics which are suggestively based on the interference with essential
      steps in the host cell kinase cascades.

PMID- 11976734
TI  - Allelic polymorphisms in the FcgammaRIIC gene can influence its function on
      normal human natural killer cells.
AB  - Natural killer (NK) cells are important in host defense against viruses and
      tumors and can induce death of virally infected cells following engagement of
      cell surface receptors. Human NK cells express receptors for the Fc portion of
      IgG which stimulate antibody-dependent cell-mediated cytotoxicity and induce
      cytokine production. We have shown that NK cells from certain individuals can
      express, in addition to CD16 (FcgammaRIIIa), isoforms of CD32 (FcgammaRIIc1-4).
      Expression of CD32 on NK cells is dependent on an allelic polymorphism of the
      FcgammaRIIC gene. We analyzed the expression and function of CD32 on NK cells
      from 31 normal donors. Fourteen of the 31 (45%) donors expressed CD32 on their NK
      cells. Molecular characterization of FcgammaRIIc isoforms expressed by the CD32+
      donors revealed that the majority of donors expressed the FcgammaRIIc1 isoform.
      Interestingly, 3 of the 14 positive donors did not express FcgammaRIIc1, and we
      identified a novel isoform, FcgammaRIIc5, expressed by these individuals. The
      expression of this isoform was correlated to a second allelic polymorphism that
      controls exon splicing. One of the three was found to express FcgammaRIIb on the
      NK cells. Biochemical analysis revealed that CD32+ donors of both types expressed
      a 40-kDa protein, specifically immunoprecipitated by anti-CD32 monoclonal
      antibodies. Functionally, only individuals expressing the FcgammaRIIc1 isoform
      were able to trigger reverse antibody-dependent cell-mediated cytotoxicity via
      CD32 whereas a CD32+ individual expressing the FcgammaRIIb isoform was unable to
      trigger this function. These results demonstrate that the presence of multiple
      allelic polymorphisms in the FcgammaRIIC gene determine the expression and
      function of CD32 on NK cells.

PMID- 11976733
TI  - A comparative study of Greek nondeletional hereditary persistence of fetal
      hemoglobin and beta-thalassemia compound heterozygotes.
AB  - The coexistence of beta- and gamma-globin gene mutations in the compound
      heterozygous state presents a rare in vivo model that provides important data on
      gene regulation of clinical interest. In this unique comparative study we present
      the hematological, biosynthetic, and molecular data from six adult compound
      heterozygotes for the Greek nondeletional hereditary persistence of fetal
      hemoglobin (nd-HPFH, Agamma-117 G-->A) and four frequent beta-thalassemia
      mutations (IVS I-110 G-->A, Cd 39 C-->T, IVS I-1 G-->A, and IVS I-6 T-->C) found
      in the Hellenic population. Fetal hemoglobin (HbF) levels were found to be
      considerably higher (25-50%) than in 19 Greek nd-HPFH heterozygotes (HbF=9.7+/
      1.7%) and, interestingly, to depend on the type of the respective beta
      thalassemia mutation, in trans to the nd-HPFH allele. All cases presented a
      typical beta-thalassemia heterozygote's phenotype despite the increased HbF and
      the normal HbA2 levels, as indicated by both the hematological indices and the
      biosynthetic ratios. These data were compared with those from two unique cases of
      Greek origin: a homozygous case of the Greek nd-HPFH and a compound heterozygote
      with HbS. Our data suggest that in these compound heterozygous cases the beta
      thalassemic chromosome indirectly determines the final outcome of the gamma- and
      of the in cis beta-globin gene expression, most likely at the post
      transcriptional level.

PMID- 11976736
TI  - Percutaneous renal artery embolisation of non-functioning renal allografts with
      clinical intolerance.
AB  - The aim of the study was to evaluate the efficacy and safety of percutaneous
      renal artery embolisation of non-functioning renal allografts in patients with
      graft intolerance syndrome (GIS). Transcatheter artery embolisation was performed
      in 30 kidney transplant recipients with GIS. The duration of graft function had
      been 60+/-45 months. Infectious disease was ruled out in all patients.
      Embolisation consisted of the injection of polyvinyl alcohol microspheres
      followed by the insertion of a stainless steel coil in the renal artery branches.
      Symptoms of GIS included: fever-graft pain (44%, n=13), fever-hematuria-pain
      (20%, n=6), fever-hematuria (13%, n=4) and fever alone (23%, n=7). Latency time
      between graft failure and embolisation was 184+/-227 (17-1181) days. Embolisation
      was clinically successful with the prolonged disappearance of GIS in 24 patients
      (80%). Six patients showed initial clinical improvement, but GIS reappeared at
      40+/-18 days, and graft nephrectomy was required. There were no major
      complications associated with embolisation and no deaths. Perirenal collateral
      supply was a risk factor for the reappearance of GIS. Renal vascular embolisation
      is a simple, safe and effective technique for treating renal allograft
      intolerance syndrome and could be a feasible alternative for the first-line
      treatment.

PMID- 11976735
TI  - The Ets 1 transcription factor is upregulated during inflammatory angiogenesis in
      rheumatoid arthritis.
AB  - Neovascularization of the inflamed synovium and pannus is one of the hallmarks of
      chronic rheumatoid arthritis. It contributes to disease progression by supplying
      blood to the inflamed tissues and by recruiting immune competent and inflammatory
      cells. Angiogenesis is tightly regulated at several levels, but of significant
      importance is transcription. The Ets 1 transcription factor has been intimately
      linked to the regulation of angiogenesis under both physiological and
      pathological conditions and is induced in endothelial cells by vascular
      endothelial growth factor, the most important angiogenic factor in rheumatoid
      arthritis. We investigated Ets 1 expression in synovial membranes of joints in
      patients with active rheumatoid arthritis and compared the results to those
      obtained in patients with degenerative joint disease, which is characterized by
      significantly less neoangiogenesis. Using quantitative densitometric and real
      time RT-PCR approaches, we found a significant upregulation of Ets 1 transcripts
      in rheumatic, compared to osteoarthritic, synovial membranes. Moreover, we were
      able to attribute both Ets 1 mRNA and Ets 1 protein to capillary endothelial
      cells of newly formed blood vessels by in situ hybridization and
      immunohistochemistry. Finally, our data suggest important roles of the Ets 1
      transcription factor in the regulation of inflammatory angiogenesis in rheumatoid
      arthritis.

PMID- 11976737
TI  - Hepatocyte growth factor (HGF) as a rapid diagnostic marker and its potential in
      the prevention of acute renal rejection.
AB  - Several investigators have reported that hepatocyte growth factor (HGF) may be
      related to the protection or reconstruction of the kidney during acute renal
      rejection. To address this question, we examined the relationship between HGF and
      acute rejection in the following two studies with rat renal transplantation
      models. In study 1, the relationship between serum HGF levels and acute renal
      rejection in iso-, allo- and allograft with cyclosporine (CsA)-treated models was
      examined. In study 2, the focus was whether or not the injection of recombinant
      HGF can prevent acute renal rejection. Our results demonstrated that HGF levels
      were rapidly increased during acute rejection and that recombinant HGF
      effectively protected the kidney from acute rejection. These results suggest that
      HGF may be induced as a counter-response to the renal injury and that it can be
      used as a reliable indicator for the diagnosis of acute rejection. We suggest
      that recombinant HGF suppresses the onset of the pathological changes of acute
      rejection.

PMID- 11976739
TI  - Microcirculatory events in ischemia/reperfusion of the pancreas defined by
      continuous tissue oximetry.
AB  - In ischemia/reperfusion of the pancreas impairment of microcirculation after
      reperfusion is believed to be of critical importance. The 'no-reflow' phenomenon
      is thought to cause persisting tissue ischemia, while the 'reflow-paradox' is
      defined as secondary impairment of nutritive perfusion. These phenomena have been
      shown by intravital microscopy but their effect on tissue oxygenation as assessed
      by continuous tissue oximetry has not been identified. In landrace pigs tissue
      oxygenation was investigated in warm ischemia/reperfusion of the pancreas by the
      use of continuous tissue oximetry. After reperfusion rapid reoxygenation occurred
      which was followed by a period of secondary hypoxia. Thereafter, secondary
      reoxygenation was found, and finally tertiary hypoxia with a gradual decline of
      tissue pO(2) was noted. The data show a relevant impairment of tissue oxygenation
      after reperfusion. However, 'no-reflow' seems not to be a primary failure of
      capillary reperfusion but the consequence of a short reperfusion period followed
      by secondary ischemia. The 'reflow-paradox' most likely corresponds to tertiary
      ischemia.

PMID- 11976738
TI  - Lipopolysaccharide-binding protein as a new and reliable infection marker after
      kidney transplantation.
AB  - The early and reliable differentiation of rejections, viral infections and
      bacterial infections is one of the main problems after organ transplantation. One
      promising solution to this problem is the lipopolysaccharide-binding protein
      (LBP), which is regulated upwards in gram-negative sepsis and related conditions.
      Therefore, the aim of our study was to explore the diagnostic potential of LBP
      serum levels in well-defined, non-infectious and infectious events after kidney
      transplantation (KTx). In a retrospective study the LBP serum levels were
      measured in a total of 686 serum samples from 52 kidney graft recipients. In all
      pre-KTx sera tested, the mean LBP level was 8.8+/-3.5 microg/ml (reference range:
      2.0-15.2 microg/ml). In 7 of 52 recipients without intraoperative T-cell
      depletion, the mean LBP level was significantly ( P<0.01) increased (13.0+/-1.5
      microg/ml) at post-KTx day 1, but was within the reference range. In contrast,
      the intraoperative T-cell depletion by antilymphocyte antibodies resulted in a
      significant ( P<0.01) increase to 25.8+/-11.4 microg/ml (range: 13.3-47.2
      microg/ml). In recipients with immediate ( n=14) or delayed ( n=9) graft function
      without any other complications, all post-KTx values (except the post-KTx peak)
      were within the reference range. In 10 recipients with steroid-sensitive
      rejections and in 11 recipients with steroid-resistant rejections, no rejection
      associated changes of the LBP levels could be shown. In six recipients with
      cytomegalovirus infection, the detection of an antigenemia (pp65) also was not
      associated with alterations of the LBP levels. In addition, there was no
      correlation between LBP levels and the number of pp65-positive leukocytes in
      peripheral blood. In contrast, a strong elevation of LBP levels was seen in five
      recipients with gram-positive bacteremia as well as in other severe bacterial
      infections (e.g., purulent extravasate, heavily infected grafts, bacterial
      pneumonia and contaminated hematoma). In two recipients with superinfected
      (bacterial and mycotic or viral) Pneumocystis carinii pneumonias requiring
      assisted ventilation, LBP levels were elevated, too. Thus, in our study only
      systemic non-viral infections and massive lymphocytolysis were associated with
      elevated LBP serum levels.

PMID- 11976742
TI  - Current opinions in horseshoe kidney transplantation.
AB  - Currently, horseshoe kidneys are also being considered for transplantation due to
      the shortage of organs. They can be transplanted en bloc or after division of the
      renal isthmus. However, because of their low incidence, horseshoe kidneys are
      rarely transplanted. The considerable variation in vascular anatomy of the
      horseshoe kidney add to both the frequency of primary non-function and the
      technical difficulty of the transplantation. In the study reported here, the
      surgical members of the European Society for Organ Transplantation were asked for
      their opinions regarding the techniques and results of horseshoe kidney
      transplantation. Most surgeons advised explanting the horseshoe kidney en bloc.
      The decision to transplant en bloc or after division of the renal isthmus
      depended on the morphology of the renal isthmus, the number and position of renal
      vessels and/or the anatomy of the urinary collecting system. Most surgeons
      thought that the results of horseshoe kidney transplantation were equal to those
      of normal kidneys.

PMID- 11976740
TI  - Structural skeletal impairment induced by immunosuppressive therapy in rats:
      cyclosporine A vs tacrolimus.
AB  - The exact role of immunosuppressive drugs in the development of osteoporosis and
      pathologic fractures frequently reported in patients following organ
      transplantation is still not known. In two experiments, the effects of
      immunosuppressive drugs were studied on growing rats allocated randomly into five
      groups of eight rats each which received either FK506 (1.5 mg/kg or 3 mg/kg) or
      cyclosporine A (15 mg/kg or 30 mg/kg) for 28 days by daily oral gavage. In
      experiment I ( n=40), bone mineral content (BMC) of the femur by dual energy X
      ray absorptiometry (DXA), and bone ash weight were measured. In experiment II (
      n=40), stereologic measurements of decalcified tibiae were carried out. The BMC
      and ash weight values of the whole femur were significantly lower both in the low
      and high-dose FK506 groups as well as in the high-dose CsA group. Decalcified
      sections showed lower volume density of trabecular bone of the tibial metaphysis
      in both CsA-treated groups and in the high-dose FK506 group. Furthermore, the
      volume density of the hypertrophic zone volume of the growth plate was higher in
      high-dose CsA-treated rats. Our data demonstrate that both CsA and FK506 have
      adverse effects on bone and that high doses of CsA or FK506 alter both cortical
      and trabecular bone with subsequent osteopenia. In addition, CsA-treated groups
      showed histological changes in some aspect resembling rickets/osteomalacia.

PMID- 11976741
TI  - Persistence of mild parkinsonism 4 months after liver transplantation in patients
      with preoperative minimal hepatic encephalopathy: a study on neuroradiological
      and blood manganese changes.
AB  - Pallidal hyperintensity at magnetic resonance imaging (MRI) correlates to blood
      manganese (Mn) levels and parkinsonian signs in patients with cirrhosis.
      Similarly, metabolite changes in the basal ganglia (BG) at proton spectroscopy
      are related to these neurological signs. The evolution of these abnormalities
      after liver transplantation (OLT) is incompletely described. We evaluated 14
      unselected consecutive patients with cirrhosis (minimal hepatic encephalopathy
      [HE] n=8, no HE n=6) before and 4 months after successful OLT for the evolution
      of parkinsonism using a validated scale (the United Parkinson's Disease Rating
      Scale, or UPDRS). Pallidal intensity at MRI, spectroscopic changes in the BG at
      magnetic resonance spectroscopy (MRS), and whole blood manganese concentrations
      were measured. After OLT in patients with preoperative minimal HE, the UPDRS
      scores improved, but mild parkinsonism persisted (16.1+/-3.6 to 6.2+/-4.8,
      P<0.05). Pallidal hyperintensity remained abnormal in 5/8 of cases, but
      spectroscopic changes normalized in all patients. Blood Mn remained elevated in
      4/6 patients. In patients without HE, UPDRS values remained negligible (2.42+/
      1.5 to 2.5+/-1.4). Pallidal hyperintensity normalized in 7/8 patients and
      spectroscopic changes normalized in all patients. Blood Mn remained elevated in
      5/6 patients. Four months after successful OLT, patients with preoperative
      minimal HE and severe pallidal hyperintensity showed persistent mild
      parkinsonism. The role of blood manganese determination appears limited in the
      monitoring of MRI and parkinsonian signs changes after OLT.

PMID- 11976743
TI  - Human islet retransplantation in a patient with type I diabetes.

PMID- 11976745
TI  - Polyphasic characterization of benthic, moderately halophilic, moderately
      thermophilic cyanobacteria with very thin trichomes and the proposal of
      Halomicronema excentricum gen. nov., sp. nov.
AB  - A new genus of moderately halophilic, moderately halotolerant and moderately
      thermophilic cyanobacteria with very thin trichomes is described. The four
      strains included in this genus were isolated from benthic microbial mats in a man
      made hypersaline pond. Trichomes were around 1 microm thick, with small
      constrictions at the cross-walls and diffluent colorless sheaths. Thylakoids were
      parallel to the cell wall, but thylakoids and nucleoid were often excentrically
      arranged within the cytoplasm with respect to the main trichome axis. Strains
      grew at between 3.2 and 12-15% (w/v) salinity with optima between 3.2 and 12%.
      They showed lower temperature limits around 20 degrees C and upper limits between
      45 and 50 degrees C, with optima between 28 and 45-50 degrees C. Carotenoid and
      mycosporine amino-acid complements were identical among strains. Phylogenetic
      analyses based on 16S rRNA gene sequence showed that all strains were closely
      related (99% or higher similarity) and distantly related to other cyanobacteria
      (91% or lower similarity). We propose the new genus and species Halomicronema
      excentricum for these strains. The type strain is TFEP1.

PMID- 11976746
TI  - Evaluation of non-cyanobacterial genome sequences for occurrence of genes
      encoding proteins homologous to cyanophycin synthetase and cloning of an active
      cyanophycin synthetase from Acinetobacter sp. strain DSM 587.
AB  - All publicly accessible microbial genome databases were searched for the
      occurrence of genes encoding proteins homologous to the cyanophycin synthetase
      (CphA) of Synechocystis sp. strain PCC 6803 in order to reveal the capability of
      microorganisms not belonging to the cyanobacteria to synthesize cyanophycin.
      Among 65 genome sequences, genes homologous to cphA were found in Acinetobacter
      sp. strain ADP1 (encoding a protein homologous to CphA with 40% amino acid
      identity), Bordetella bronchiseptica strain RB50 (39%), Bordetella pertussis
      strain Tohama I (39%), Bordetella parapertussis strain 12822 (39%), Clostridium
      botulinum strain ATCC 3502 (39%), Desulfitobacterium hafniense strain DCB-2 (38%)
      and Nitrosomonas europaea strain ATCC 25978 (37%). The gene homologous to cphA
      from Acinetobacter sp. strain DSM 587 was amplified by PCR, ligated to the vector
      pBluescript SK(-) downstream of the lac promoter and introduced into Escherichia
      coli. The recombinant strain of E. coli expressed CphA activity at up to 1.2 U/mg
      protein and accumulated cyanophycin to up to 7.5% of the cellular dry matter,
      indicating that CphA of Acinetobacter sp. strain DSM 587 is functionally active.
      In Acinetobacter sp. strain DSM 587 itself, cyanophycin accumulated to up to 1.4%
      of the total protein under phosphate-limited conditions, and cyanophycin
      synthetase activity was detected, which indicated the function of cyanophycin as
      a storage compound in this strain.

PMID- 11976747
TI  - Desulfotignum phosphitoxidans sp. nov., a new marine sulfate reducer that
      oxidizes phosphite to phosphate.
AB  - A new sulfate-reducing bacterium was isolated from marine sediment with phosphite
      as sole electron donor and CO(2) as the only carbon source. Strain FiPS-3 grew
      slowly, with doubling times of 3-4 days, and oxidized phosphite, hydrogen,
      formate, acetate, fumarate, pyruvate, glycine, glutamate, and other substrates
      nearly completely, with concomitant reduction of sulfate to sulfide. Acetate was
      formed as a side product to a small extent. Glucose, arabinose, and proline were
      partly oxidized and partly fermented to acetate plus propionate. Growth with
      phosphite, hydrogen, or formate was autotrophic. Also, in the presence of
      sulfate, CO dehydrogenase was present, and added acetate did not increase growth
      rates or growth yields. In the absence of sulfate, phosphite oxidation was
      coupled to homoacetogenic acetate formation, with growth yields similar to those
      in the presence of sulfate. Cells were small rods, 0.6 - 0.8 x 2-4 microm in
      size, and gram-negative, with a G+C content of 53.9 mol%. They contained
      desulforubidin, but no desulfoviridin. Based on sequence analysis of the 16S rRNA
      gene and the sulfite reductase genes dsrAB, strain FiPS-3 was found to be closely
      related to Desulfotignum balticum. However, physiological properties differed in
      many points from those of D. balticum. These findings justify the establishment
      of a new species, Desulfotignum phosphitoxidans.

PMID- 11976748
TI  - Effects of nitrogen availability on pigmentation and carbon assimilation in the
      cyanobacterium Synechococcus sp. strain SH-94-5.
AB  - Because pigments of phototrophs can be involved either in photosynthesis or
      photoprotection, pigmentation changes in response to nutrient availability can
      affect how cells interact with their solar environment. We investigated the
      impact of nitrogen availability both on pigmentation of the cyanobacterium
      Synechococcus sp. strain SH-94-5 and on carbon assimilation by this strain in the
      presence or absence of UV radiation. Pigmentation changes in strain SH-94-5 due
      to ammonium exhaustion included phycobiliprotein degradation, an exponential
      decline in chlorophyll a content, and a net increase in beta-carotene. Following
      its replenishment, ammonium stimulated non-photosynthetic carbon assimilation for
      several hours prior to the resumption of photosynthesis and growth. Carbon
      fixation during this lag phase was concurrent with the metabolism of glycogen
      reserves, and it is likely that inorganic carbon was incorporated into glycogen
      derived carbon skeletons primarily for amino acid synthesis. In contrast, carbon
      fixation was almost exclusively photosynthetic during exponential growth. UV-A
      radiation (320-400 nm) inhibited photosynthetic but not non-photosynthetic carbon
      assimilation. Only growing cells were inhibited, and the disappearance of
      inhibition following nitrogen depletion appeared to result from the reduction of
      cellular photosensitizing targets below a threshold level rather than from the
      inactivation of photosynthesis.

PMID- 11976749
TI  - ATP-dependent 6-phosphofructokinase from the hyperthermophilic bacterium
      Thermotoga maritima: characterization of an extremely thermophilic,
      allosterically regulated enzyme.
AB  - The ATP-dependent 6-phosphofructokinase (ATP-PFK) of the hyperthermophilic
      bacterium Thermotoga maritimawas purified 730-fold to homogeneity. The enzyme is
      a 140-kDa homotetramer composed of 34 kDa subunits. Kinetic constants were
      determined for all substrates in both reaction directions at pH 7 and at 75
      degrees C. Rate dependence (forward reaction) on fructose 6-phosphate (F-6-P)
      showed sigmoidal kinetics with a half-maximal saturation constant ( S(0.5)) of
      0.7 mM and a Hill coefficient of 2.2. The apparent K(m) for ATP was 0.2 mM and
      the apparent V(max) value was about 360 U/mg. The enzyme also catalyzed in vitro
      the reverse reaction with an apparent K(m) for fructose 1,6-bisphosphate and ADP
      of 7.6 mM and 1.4 mM, respectively, and an apparent V(max) of about 13 U/mg.
      Divalent cations were required for maximal activity; Mg(2+), which was most
      effective, could partially be replaced by Mn(2+) and Fe(2+). Enzyme activity was
      allosterically regulated by classical effectors of ATP-PFKs of Eukarya and
      Bacteria; it was activated by ADP and inhibited by PEP. The enzyme had a
      temperature optimum of 93 degrees C and showed a significant thermostability up
      to 100 degrees C. Using the N-terminal amino acid sequence of the subunit, the
      pfk gene coding for ATP-PFK was identified and functionally overexpressed in
      Escherichia coli. The purified recombinant ATP-PFK had identical kinetic and
      allosteric properties as the native enzyme purified from T. maritima. The deduced
      amino acid sequence showed high sequence similarity to members of the PFK-A
      family. In accordance with its allosteric properties, ATP-PFK of T. maritima
      contained the conserved allosteric effector-binding sites for ADP and PEP.

PMID- 11976750
TI  - Two class II D-tagatose-bisphosphate aldolases from enteric bacteria.
AB  - Escherichia coli, Salmonella enterica, Klebsiella pneumoniaeand Klebsiella
      oxytocawere found to contain two D-tagatose 1,6-bisphosphate (TagBP)-specific
      aldolases involved in catabolism of galactitol (genes gatY gatZ) and of N-acetyl
      galactosamine and D-galactosamine (genes kbaY kbaZ,also called agaY agaZ). The
      two aldolases were closely related (> or = 53.8% identical amino acids) and could
      substitute for each other in vivo. The catalytic subunits GatY or KbaY alone were
      sufficient to show aldolase activity. Although substantially shorter than other
      aldolases (285 amino acids, instead of 358 and 349 amino acids), these subunits
      contained most or all of the residues that have been identified as essential in
      substrate/product recognition and catalysis for class II aldolases. In contrast
      to these, both aldolases required subunits GatZ or KbaZ (420 amino acids) for
      full activity and for good in vivo and in vitro stability. The Z subunits alone
      did not show any aldolase activity. Close relatives of these new TagBP aldolases
      were found in several gram-negative and gram-positive bacteria, e.g.,
      Streptomyces coelicolor.

PMID- 11976751
TI  - Tetrachloroethene reductive dehalogenase of Dehalospirillum multivorans:
      substrate specificity of the native enzyme and its corrinoid cofactor.
AB  - The substrate specificity of the tetrachloroethene reductive dehalogenase of
      Dehalospirillum multivoransand its corrinoid cofactor were studied. Besides
      reduced methyl viologen, titanium(III) citrate could serve as electron donor for
      reductive dehalogenation of tetrachloroethene (PCE) and trichloroethene to cis
      1,2-dichloroethene. In addition to chlorinated ethenes, chlorinated propenes were
      reductively dechlorinated solely by the native enzyme. trans-1,3-Dichloropropene,
      1,1,3-trichloropropene and 2,3-dichloropropene were reduced to a mixture of mono
      chloropropenes, 1,1-dichloropropene, and 2-chloropropene, respectively. Other
      halogenated compounds that were rapidly reduced by the enzyme were also
      dehalogenated abiotically by the heat-inactivated enzyme and by commercially
      available cyanocobalamin. The rate of this abiotic reaction was dependent on the
      number and type of halogen substituents and on the type of catalyst. The
      corrinoid cofactor purified from the tetrachloroethene dehalogenase of D.
      multivorans exhibited an activity about 50-fold higher than that of
      cyanocobalamin (vitamin B(12)) with trichloroacetate as electron acceptor,
      indicating that the corrinoid cofactor of the PCE dehalogenase is not
      cyanocobalamin. Corrinoids catalyzed the rapid dehalogenation of trichloroacetic
      acid. The rate was proportional to the amount of, e.g. cyanocobalamin; therefore,
      the reductive dehalogenation assay can be used for the sensitive and rapid
      quantification of this cofactor.

PMID- 11976754
TI  - Tactile interference in visually guided reach-to-grasp movements.
AB  - This study addresses the issue of cross-modal links in goal-directed actions and
      specifically the influence of non-relevant tactile information on visually guided
      reach-to-grasp movements. Right-handed participants reached for and grasped with
      either their left or right hand a visually presented, midsagitally placed target.
      The target was presented alone, or was accompanied by an unseen, tactile
      distractor placed in the non-reaching hand. The tactile distractor was either
      smaller than, the same size as or larger than the target. Significant alterations
      in kinematic parameterisation were restricted to the grasp component of the
      movement, and specifically to the reaching right hand. More importantly, the size
      of the unseen tactile distractors in the left hand altered the grasp
      parameterisation of the right hand. These findings are discussed in the context
      of current theories of the control of action by perceptual processes.

PMID- 11976752
TI  - Influence of biosolids compost on the bradyrhizobial genotypes recovered from
      cowpea and soybean nodules.
AB  - The interaction of biosolids compost application to soil and bradyrhizobial
      genotypes recovered from nodules was examined. Among 170 isolates, seven
      genotypes were recovered from soils receiving either no biosolids application or
      rates of 73 or 146 Mg/ha for three successive years. With the exception of one
      genotype, the distribution of the bacterial genotypes recovered from nodules was
      interrelated with the level of biosolids. Two of the genotypes nodulated both
      soybean and cowpea. Because soybean-nodulating bradyrhizobia were not recovered
      from control plots, it is possible that they had been introduced together with
      the biosolids compost application.

PMID- 11976755
TI  - Effects of pallidal deep brain stimulation and levodopa treatment on reaction
      time performance in Parkinson's disease.
AB  - Basal ganglia-thalamocortical circuits play an important role in movement
      preparation and execution. Tracer, single-cell, and lesion studies in monkeys
      suggest the existence of topologically segregated motor and nonmotor basal
      ganglia cortical circuits. In this study we used deep brain stimulation (DBS) of
      the posteroventrolateral globus pallidus internus (GPi) in patients with
      Parkinson's disease to elucidate the function of the GPi in human sensorimotor
      behavior. This question was investigated by comparing the influence of DBS on
      patients' performance in various reaction-time tasks that differed with respect
      to cognitive but not motor requirements. As a main result, DBS improved
      performance on the different tasks independently of the complexity of the
      involved cognitive processing functions. Furthermore, the observed effects did
      not depend on the modality of the processed information. These results suggest
      that the functional state of the posteroventrolateral GPi selectively affects the
      motor stage in simple sensorimotor acts, because this stage was the only stage
      involved in all investigated tasks. In addition to DBS, we manipulated the
      levodopa medication state of the PD patients. In contrast to DBS, levodopa
      effects on reaction times were less consistent. Levodopa improved reaction times
      in choice reaction tasks significantly, while affecting reaction times in a
      simple reaction task to a lesser extent. Error analysis revealed that the
      medication-dependent reaction-time improvement in the choice reaction tasks was
      accompanied by an increase in errors, suggesting a shift of the speed-accuracy
      criteria of the patients. A similar pattern of results was not observed for the
      DBS effects. Taken together, our data are in agreement with recent findings in
      monkeys that indicate a topological organization of the GPi in which motor
      functions are localized in posterolateral regions apart from cognitive regions.
      Furthermore, our data show a way to uncover the subcortical-cortical circuitry
      serving human sensorimotor behavior.

PMID- 11976756
TI  - Effects of stimulus-induced saccades on manual response times in healthy elderly
      and in patients with right-parietal lesions.
AB  - Response delays of hemi-neglect patients to invalidly cued left targets in
      Posner's visual cueing task have been interpreted as reflecting disorders of
      covert attention, although shifts of overt attention have so far not been
      systematically measured in patients performing this task. Therefore, we measured
      saccades (i.e., fast goal-directed eye movements) induced by cues and targets in
      this task in ten patients with lesions of the right posterior parietal cortex and
      in age-matched healthy subjects. Participants were not aware that their saccades
      were studied. Of greatest interest was whether the presence or absence of
      saccades would modify the patients' response delay with invalidly cued left
      targets. In both groups, saccades occurred in many trials, key-press responses
      were slower in saccade trials than in no-saccade trials, and the delay by invalid
      cues was larger in saccade trials. The patients' responses were in particular
      delayed if preceded by saccades to the left. Their delay to invalidly cued left
      targets almost doubled (144 ms vs 76 ms) when only saccade trials were analyzed
      compared to when only no-saccade trials were analyzed. Thus, overt shifts
      (saccades) have a similar but larger effect on manual responses than covert
      shifts of attention. In particular, overt shifts make a considerable contribution
      to the patients' pathological delay of responses to invalidly cued left targets.

PMID- 11976759
TI  - Effects of cytotoxic nucleus accumbens lesions on instrumental conditioning in
      rats.
AB  - In two experiments the involvement of the nucleus accumbens in instrumental
      conditioning was investigated using rats as subjects. In experiment 1, extensive
      bilateral cytotoxic lesions of the nucleus accumbens mildly suppressed
      instrumental responding reinforced with food, but had no detectable effect on the
      sensitivity of the rats' performance either to outcome devaluation or to
      degradation of the instrumental contingency. In experiment 2, restricted
      accumbens lesions reliably attenuated the excitatory effect of systemically
      administered d-amphetamine on lever pressing for a conditioned reinforcer, and
      completely abolished Pavlovian-instrumental transfer. Taken together these
      results give a picture of the involvement of the rat nucleus accumbens in
      instrumental conditioning. They support the widely held theory that the nucleus
      accumbens mediates the excitatory effects of appetitively conditioned Pavlovian
      signals on instrumental performance and refute the hypothesis that the nucleus
      accumbens is part of the neural circuitry by which incentive value is attached to
      the representations of instrumental outcomes.

PMID- 11976758
TI  - Force synergies for multifingered grasping: effect of predictability in object
      center of mass and handedness.
AB  - To grasp with five digits of the hand requires an efficient parceling of contact
      forces in order to maintain static equilibrium as an object is lifted and held.
      In a previous study, subjects were asked to reach, grasp and lift a five-digit
      grip apparatus whose center of mass (CM) location was changed for each block of
      trials. Despite a modulation of force sharing patterns among the digits as a
      function of center of mass location, consistent in-phase and out-of-phase
      relationships between normal forces were found in the frequency domain. In the
      present study, we have used the same task to assess the effect of (a)
      predictability of an object's CM location (random vs blocked presentation) and
      (b) handedness (dominant vs non-dominant hand). Contrary to our original
      expectations, we found a similar modulation of normal forces to CM location
      during the hold phase across all conditions. Specifically, the force sharing
      pattern, i.e., the rank order of force contributed by each digit, emerged very
      early in the grasp sequence, remaining relatively stable throughout the duration
      of the lift and hold. Nevertheless, the extent to which force sharing patterns
      could be discriminated as a function of CM location was lower in the random than
      in the blocked conditions. Lastly, normal forces exerted by pairs of digits
      tended to be synchronized, both in-phase (thumb and fingers) and out-of-phase
      (pairs of digits) across a large proportion of the functional frequency range (up
      to 10 Hz) in all conditions. The composite of these findings suggests that the
      central nervous system uses stereotyped control strategies for coordinating
      multiple grip forces during grasping. Specific aspects of these schemes appear to
      be affected by predictability of object CM location, but not by hand dominance.

PMID- 11976757
TI  - Increased afterdischarge threshold during kindling in epileptic rats.
AB  - The effects of daily electrical kindling stimulation of the perforant pathway
      were investigated in an excitotoxic rat model of epilepsy with chronic seizures
      in order to learn whether the preexisting epileptic condition would facilitate or
      retard kindling. Sprague-Dawley rats with recurrent spontaneous seizures 4-8
      months after unilateral intrahippocampal kainic acid (KA) injection were
      implanted with recording electrodes in the hippocampus and stimulating electrodes
      in the perforant path. Daily stimulation for 10 s at 5 Hz was given for 15 days.
      The afterdischarge (AD) threshold and the AD duration of kindled KA rats were
      compared before and during kindling with those of a kindled control group. In the
      control group, as expected, mean AD thresholds decreased ( P<0.01), while AD
      duration progressively increased. Although AD threshold was the same in KA and
      control groups at the start of kindling, in the KA group a significant increase
      in threshold occurred from the beginning to the end of kindling ( P<0.01).
      Behaviorally, KA rats showed stage 4 or 5 seizures on the first stimulation, and
      stage 3-5 seizures during the remainder of kindling. Paired pulse testing showed
      facilitation of late components of the dentate gyrus field potential at the
      beginning of kindling, and suppression of late components at the end, in the KA
      rats. A significant decrease in the rate of spontaneous seizures in KA rats was
      noted during the period of kindling ( P=0.04). These results suggest that
      electrical stimulation of the perforant path may strengthen homeostatic seizure
      suppressing mechanisms, and may provide insights into novel approaches to the
      treatment of clinical seizures in temporal lobe epilepsy.

PMID- 11976760
TI  - Between-subject variability and within-subject reliability of the human eye
      movement response to bilateral galvanic (DC) vestibular stimulation.
AB  - Recent studies have shown that responses to surface galvanic vestibular
      stimulation (GVS) show substantial interindividual variation. Between-subject
      variability may be due to individual differences between subjects, or to the poor
      reliability of the test, or to differences in test details, or to host factors.
      The aim of the present study was to compare variability between and within
      subjects in binocular 3-D eye-movement responses to long-duration, maintained,
      large-amplitude, bilateral, bipolar, surface GVS. Subjects were seated and
      restrained, and in one condition fixated a small, centrally located visual
      target; in the other condition, testing was carried out in complete darkness.
      Surface GVS of 5 mA, with a rectangular waveform was delivered bilaterally for 5
      min while eye movements were measured using computerised video-oculography (VTM).
      In the first experiment, ten subjects participated in both conditions in one
      session, and in the second experiment, two subjects participated in both
      conditions for a total of five repeated sessions. The stimulation was well
      tolerated by all subjects and produced a change in torsional position with the
      upper pole of both eyes rolling towards the anode and away from the cathode in
      all subjects in both conditions. Although little vertical nystagmus was evident
      in either condition, most subjects showed relatively strong horizontal nystagmus
      (slow phases towards the anode) in darkness. This study confirms previous
      observations that the torsional response to GVS is highly variable between
      subjects, whilst also showing for the first time that eye-movement responses to
      GVS show good within-subject repeatability. This study also demonstrates
      considerable between-subject variability in the relative ratios of response
      components (torsional and horizontal nystagmus, torsional position), whereas the
      relatively small within-subject variability can be characterised more by changes
      in the overall amplitude of the eye-movement response. Subjects show
      idiosyncratic oculomotor response patterns to GVS, varying slightly in absolute
      magnitude between sessions. Thus, GVS may be a more reliable stimulus than may
      have been anticipated from the literature.

PMID- 11976761
TI  - Perforant path lesioning induces sprouting of CA3-associated fibre systems in
      mouse hippocampal formation.
AB  - In comparison to the rat, the anatomy of the mouse hippocampus, and in particular
      the response to entorhinal cortex lesioning, is less well characterised. Here we
      studied the axonal sprouting response after lesioning of the entorhinodentate
      perforant path projection in young adult SJL/J and C57BL/6 mice. We found that
      lesioning led to translaminar sprouting of Timm stained regio inferior
      hippocampus (CA3)-associated fibre systems into the denervated termination zones
      of the CA3 and dentate gyrus, from the adjacent non-denervated stratum radiatum
      of CA3. Differences were seen in the Timm staining pattern of the two strains of
      mice, while the response to lesioning appeared similar albeit less pronounced
      than that observed in the rat. We also observed an intensified acetylcholine
      esterase staining reflective of cholinergic sprouting in the denervated perforant
      path termination zones, which was particularly prominent in areas with sprouting
      of Timm stained CA3-associated fibres. Finally, we showed that some of the
      sprouting fibres within the CA3 were myelinated, due to an increased density of
      silver impregnated myelinated fibres in this region after lesioning. These
      results show that the basic characteristics of the response to perforant path
      lesioning in mice are similar to those in the rat, but suggest that the magnitude
      of the response in the two species is different.

PMID- 11976762
TI  - Corticospinal tract transection prevents operantly conditioned H-reflex increase
      in rats.
AB  - Operant conditioning of the H-reflex, the electrical analog of the spinal stretch
      reflex, in freely moving rats is a relatively simple model for studying long-term
      supraspinal control over spinal cord function. Motivated by food reward, rats can
      gradually increase (i.e., up-condition) or decrease (i.e., down-condition) the
      soleus H-reflex. Earlier work showed that corticospinal tract transection
      prevents acquisition and maintenance of H-reflex down-conditioning while
      transection of other major spinal cord tracts does not. This study explores the
      effects on acquisition of up-conditioning of the right soleus H-reflex of mid
      thoracic transection of: the right lateral column (LC, five rats) (containing the
      rubrospinal, vestibulospinal, and reticulospinal tracts); the entire dorsal
      column (DC, six rats) [containing the main corticospinal tract (CST) and the
      dorsal ascending tract (DA)]; the CST alone (five rats); or the DA alone (seven
      rats). After initial (i.e., control) H-reflex amplitude was determined, the rat
      was exposed for 50 days to the up-conditioning mode in which reward was given
      when the H-reflex was above a criterion value. H-reflex amplitude at the end of
      up-conditioning was compared to initial H-reflex amplitude. An increase > or =20%
      was defined as successful up-conditioning. In intact rats, H-reflex amplitude at
      the end of up-conditioning averaged 164% (+/-10%, SE), and 81% were successful.
      In the present study, LC and DA rats were similar to intact rats in final H
      reflex amplitude and percent successful. In contrast, results for DC and CST rats
      were significantly different from those of intact rats. In the six DC rats, final
      H-reflex amplitude averaged 105% (+/-3)% of control and none was successful; and
      in the five CST rats, final H-reflex amplitude averaged 94% (+/-3)% and none was
      successful. The results indicate that the main CST, located in the dorsal column,
      is essential for H-reflex up-conditioning as it is for down-conditioning, while
      the dorsal column ascending tract and the ipsilateral lateral column (containing
      the main rubrospinal, vestibulospinal, and reticulospinal tracts) do not appear
      to be essential.

PMID- 11976763
TI  - Vestibular stimulation affects medium latency postural muscle responses.
AB  - This study explores whether galvanic vestibular stimulation can alter automatic
      postural muscle responses triggered 100 ms after surface translations. Our
      previous study concluded that a step of bipolar, galvanic vestibular stimulation
      delivered 500 ms prior to a platform translation tilted the internal
      representation of vertical because subjects' final center of foot pressure and
      center of mass equilibrium position shifted toward the anode and this tilt was
      larger than the sum of effects for platform translations and galvanic alone. In
      the current study, we show that 0.2-0.4 mA of galvanic vestibular stimulation
      produced significant changes in the tilt of the trunk in space that was realized
      by changes in the magnitude of the medium latency postural muscle responses at
      the ankle. The galvanic-induced changes in latency and magnitude of the first 50
      ms of gastrocnemius muscle burst in response to the backward surface translation
      were consistent with changes in background muscle tone induced by the direct
      vestibulospinal effects of the galvanic current. However, the galvanic-induced
      changes in the second 50 ms of the gastrocnemius response were in the opposite
      direction and consistent with the forward- or backward-tilted, final postural
      equilibrium goal. Kinematic analysis showed that galvanic-induced tilt was first
      initiated in the trunk and that the shank and thigh segment angles were not
      altered by galvanic stimulation prior to platform translation such that changes
      in gastrocnemius and soleus postural responses to translations were not due to an
      effect of galvanic stimulation on initial ankle angle. More proximal muscles and
      antagonist muscles involved in the postural response were not altered by the
      galvanic stimulation. These results suggest that galvanic vestibulospinal
      stimulation can alter medium latency, automatic postural responses in prime
      movers by changing the postural equilibrium goal.

PMID- 11976764
TI  - Electrical microstimulation of primate posterior parietal cortex initiates
      orienting and alerting components of covert attention.
AB  - The posterior parietal cortex (PPC) is implicated in the control of visuospatial
      orienting, including both overt saccadic eye movements and covert shifts of
      attention (i.e., attention to a location other than at visual fixation). Some
      studies have suggested that the attentional system is part of the premotor
      processing in the brain, while others suggest they are separate. Here, we test
      how the PPC controls covert attention shifts in the absence of executed eye
      movements. Electrical microstimulation was applied to the right PPC while monkeys
      performed a spatial, cued target detection task, in which they were not allowed
      to move their gaze. At high currents, contralateral saccades were evoked. With
      currents below the thresholds for eliciting saccades, microstimulation produced a
      purely attentional shift (as indexed by decreased target reaction time) when a
      cue and target were presented in the contralateral visual field. This suggests
      that microstimulation can move attention specifically in the absence of any overt
      movements of the eyes or limbs. In addition, there was a reduction in reaction
      times in trials that did not evoke attentional orienting, suggesting a more
      general alerting effect of microstimulation These data provide direct evidence
      that the PPC may be a source of both attentional modulation of neuronal responses
      and saccadic eye movements to peripheral visual stimuli.

PMID- 11976765
TI  - Comparison of receptive field expansion produced by GABA(B) and GABA(A) receptor
      antagonists in raccoon primary somatosensory cortex.
AB  - Recordings were made from 62 neurons in the forepaw representation of primary
      somatosensory cortex in anesthetized raccoons. Microiontophoretic administration
      of a specific GABA(B) receptor antagonist, CGP 55845, produced receptive field
      expansion in 74% of 46 neurons, in which it was tested first. The mean receptive
      field area was approximately doubled, with increases ranging from 12 to 500%. The
      GABA(B) receptor agonist baclofen reduced the receptive field in most (11 of 16)
      neurons, but increased the size in 4 neurons. Comparison of the effects of
      GABA(B) and GABA(A) antagonists in the same cells showed that GABA(A) receptor
      blockade produced greater expansion than GABA(B) blockade (144% vs 114%,
      respectively). Simultaneous administration of the two antagonists produced
      additional expansion in 16 of 25 neurons. There was no evidence of separate skin
      regions being masked by the two GABA receptor subtypes, as the larger expansion
      usually included the skin that was unmasked by the less effective drug. These
      results indicate that both GABA(B) and GABA(A) receptors play a role in shaping
      the normal receptive fields in somatosensory cortex.

PMID- 11976766
TI  - Investigation of age-related variations in biogenic magnetite levels in the human
      hippocampus.
AB  - The magnetic properties of human hippocampal tissue from 23 subjects (15 epilepsy
      patients and eight cadavers with no neuropathology) were analysed and tissue
      concentrations of magnetic material were calculated. The biogenic iron oxide
      magnetite (Fe(3)O(4)) is the dominant source of magnetisation in the tissue.
      Analysis of the group as a whole revealed no significant trend towards either
      increasing or decreasing magnetite concentration with age. Separate analysis of
      male and female subjects, however, reveals a trend towards increasing magnetite
      concentration with age in males. This trend is not seen in females and may have
      implications for iron metabolism and neurological disorders associated with
      disruptions in normal iron homeostasis.

PMID- 11976767
TI  - Lateralization in motor facilitation during action observation: a TMS study.
AB  - Action observation facilitates corticospinal excitability. This is presumably due
      to a premotor neural system that is active when we perform actions and when we
      observe actions performed by others. It has been speculated that this neural
      system is a precursor of neural systems subserving language. If this theory is
      true, we may expect hemispheric differences in the motor facilitation produced by
      action observation, with the language-dominant left hemisphere showing stronger
      facilitation than the right hemisphere. Furthermore, it has been suggested that
      body parts are recognized via cortical regions controlling sensory and motor
      processing associated with that body part. If this is true, then corticospinal
      facilitation during action observation should be modulated by the laterality of
      the observed body part. The present study addressed these two issues using TMS
      for each motor cortex separately as participants observed actions being performed
      by a left hand, a right hand, or a control stimulus on the computer screen. We
      found no overall difference between the right and left hemisphere for motor
      evoked potential (MEP) size during action observation. However, when TMS was
      applied to the left motor cortex, MEPs were larger while observing right hand
      actions. Likewise, when TMS was applied to the right motor cortex, MEPs were
      larger while observing left hand actions. Our data do not suggest left hemisphere
      superiority in the facilitating effects of action observation on the motor
      system. However, they do support the notion of a sensory-motor loop according to
      which sensory stimulus properties (for example, the image of a left hand or a
      right hand) directly affect motor cortex activity, even when no motor output is
      required. The pattern of this effect is congruent with the pattern of motor
      representation in each hemisphere.

PMID- 11976769
TI  - The influence of response competition on cerebral asymmetries for processing
      hierarchical stimuli revealed by ERP recordings.
AB  - It is widely accepted that the left and right hemispheres differ with respect to
      the processing of global and local aspects of visual stimuli. Recently,
      behavioural experiments have shown that this processing asymmetry strongly
      depends on the response competition between the global and local levels of a
      stimulus. Here we report electrophysiological data that underline this
      observation. Hemispheric differences for global/local processing were mainly
      observed for response-incompatible stimuli and were most prominent between 320
      and 400 ms after stimulus onset. These results underpin the idea that hemispheric
      differences are more likely to show up when a more elaborated stimulus
      representation is needed for triggering the response, that is, when a response
      conflict has to be resolved.

PMID- 11976768
TI  - Does a complex model help to understand grasping?
AB  - Several studies have demonstrated a peculiar effect of initial aperture on the
      grip formation in reach-to-grasp movements. We compare these findings with the
      predictions of two models for prehension. The first is a very simple model that
      only describes the movements of the end-effectors. The second model is rather
      complex and takes postural constraints into account. Both models can account for
      many aspects of human grasping when the movement starts with the digits in
      contact. We compare the models' performance with published data on other initial
      configurations. Both models predict an effect of initial aperture that was not
      present in the data. The model that considers postural constraints does not
      perform better than the simple model. We conclude that such constraints are not
      responsible for the main characteristics of the reach-to-grasp movement.

PMID- 11976771
TI  - Soy protein: its effects on intestinal calcium transport, serum vitamin D, and
      insulin-like growth factor-I in vvariectomized rats.
AB  - Recent reports indicate that soy protein and its isoflavones exert beneficial
      effects on bone in ovarian hormone deficiency. These positive effects, in part,
      may be due to improved intestinal calcium (Ca) absorption. We examined the role
      of soy protein or its isoflavones on intestinal Ca transport using ovariectomized
      rats. Rats were fed either a casein- or a soy protein-based diet with normal or
      depleted isoflavone levels. After 35 days of treatment, rats were exsanguinated
      and isolated cells from all intestinal segments were used to measure in vitro Ca
      transport. Ovariectomy significantly decreased the rates of Ca transport in
      duodenal and colonic cells, which were prevented by soy protein with normal
      isoflavone content. This enhanced Ca transport by isoflavones present in soy
      protein appeared to be independent of circulating insulin-like growth factor-I,
      25(OH)vitamin D, or l,25(OH)2vitamin D as these variables were unaffected by
      dietary treatments. The findings of this study imply that soy isoflavones may
      promote Ca absorption in a manner analogous to that of estrogen but without
      exerting uterotrophic effect. Further studies are needed to explore the
      mechanism(s) by which soy protein or its isoflavones promote intestinal Ca
      absorption in ovarian hormone deficiency.

PMID- 11976773
TI  - In vivo and in vitro effects of a pulsed electromagnetic field on net calcium
      flux in rat calvarial bone.
AB  - Although PEMF's have been found to promote fracture healing and to modulate the
      activity of bone cells in vitro, effects on bone metabolism are largely
      unexplored. A bioassay using neonatal rat calvarial bone was used to determine
      the early effects of a pulsing electromagnetic field (PEMF) exposure in vivo and
      in vitro on bone metabolic calcium exchange. Bone discs taken from whole body
      exposed animals (0-4 hours) show a log exposure time-dependent average increase
      in net Ca uptake in the 0-50% range (r2 = 0.83). This increase could be detected
      immediately after exposure and also after 24 hours, but not 48 hours later.
      Animals given whole body PEMF exposure also showed a decrease in serum calcium
      and did not elevate serum Ca after administration of exogenous parathyroid
      hormone (PTH). Bone discs from untreated rats, exposed to PEMF for 15 minutes in
      vitro and then assayed, showed net Ca uptake increases of a similar magnitude and
      also were refractory to the Ca-releasing effect of PTH. Unexposed discs responded
      normally to PTH by decreasing net Ca uptake. Treatment of calvarial discs with
      calcitonin or acetazolamide, both of which inactivate osteoclasts, made the bone
      refractory to further increases in Ca uptake by PEMF. These results suggest that
      PEMF exposure produces PTH-refractory osteoclastics and has a relatively rapid
      effect on increasing net bone Ca uptake, putatively due to a decrease in
      PTH/paracrine-mediated bone resorption.

PMID- 11976772
TI  - Bone mineral density and the risk of peripheral arterial disease: the Rotterdam
      Study.
AB  - Low estrogen exposure throughout life is thought to result in low bone mineral
      density (BMD) and an increased incidence of cardiovascular disease. In the
      Rotterdam Study we cross-sectionally examined the relation between BMD and
      peripheral arterial disease (PAD), as assessed by an ankle-arm index (AAI) of
      <0.9 in either leg. Data on BMD and PAD were available for 5268 individuals (3053
      women, 2215 men). From the BMD, Z-scores were calculated and subsequently divided
      into tertiles. Logistic regression analysis was used to compute odds ratios (OR)
      for PAD in tertiles of BMD, using the upper tertile as a reference. When
      adjusting for age, women with a low femoral neck BMD had a significantly
      increased risk of PAD (OR = 1.49, 95% CI 1.16-1.91). This could not be found for
      men (1.14, 0.84-1.53). The mid-tertile did not differ from the reference in
      either men or women. In women, additional adjustment for several potential
      confounders resulted in a somewhat lowered risk estimate (1.35, 1.02-1.79). In
      contrast, no association between lumbar spine BMD and PAD could be observed in
      either men or women. Our study shows an association between low femoral neck BMD
      and PAD in women only, an association unlikely to be causal. Estrogen deficiency
      may be the common denominator in osteoporosis and PAD, resulting in clustering of
      these two major diseases in postmenopausal women.

PMID- 11976776
TI  - Technological advances to extend the echocardiographic imaging of pediatric
      patients.
AB  - Recent technological advances provide significant improvement in the quality of
      imaging for the acoustically challenged pediatric patient. Although tissue
      harmonics allow better imaging of the larger or postoperative patient, high
      frequency transducers tend to optimize imaging in smaller patients.
      Miniaturization of transducers and ultrasound systems has lead to the innovative
      utilization of previously unavailable acoustic windows in a wider variety of
      settings. Each improvement advances the technology closer to the goal of
      providing optimal cardiac imaging in nearly all patients under virtually all
      circumstances.

PMID- 11976774
TI  - New ultrasound methods to quantify regional myocardial function in children with
      heart disease.
AB  - From a temporally resolved radio-frequency data set, a series of new developing
      indices of regional myocardial deformation can be measured. These may be
      important new data sets to quantify regional radial and long axis function of the
      left or right ventricle in children with acquired or congenital heart disease.
      Using color Doppler methodology unidimensional regional myocardial strain rates
      (SR) and natural strain (e) can now be calculated from local myocardial velocity
      data sets. Normal regional velocity, SR, and e values have already been
      determined in older children and should form the database for studies into
      acquired or congenital heart disease in this age group. Neonatal and infant
      values have yet to be determined. This article will present preliminary data on
      the potential clinical value of ultrasonic regional SR and e imaging in children
      and will discuss the close interrelation of these new regional function
      parameters with an alternative approach to quantification: the measurement of
      local cyclical changes in integrated backscatter levels.

PMID- 11976777
TI  - Three-dimensional echocardiography in congenital heart disease: a continuum of
      unfulfilled promises? No. A presently clinically applicable technology with an
      important future? Yes.
AB  - Three-dimensional echocardiography has important clinical applications to
      congenital heart disease. Such applications include assessment of ventricular
      volumes, and unique imaging planes and projections of septae and atrio
      ventricular and semi-lunar valves. Advances in ultrasound and computer technology
      will improve the process of three-dimensional echocardiography to continue to
      bring it to everyday clinical utility application.

PMID- 11976778
TI  - Intracardiac echocardiography in congenital heart disease: are we ready to begin
      the fantastic voyage?
AB  - Advances in and miniaturization of echocardiographic technology have led to many
      new methods of examining cardiovascular malformations. Intracardiac
      echocardiography (ICE) has reached a point where a real impact on clinical
      medicine can be anticipated. Use of ICE guidance during electrophysiologic and
      some interventional catheterization procedures will probably become standard
      clinical practice in the near future. Current results in adults and potential
      application to and limitations in the pediatric population are discussed.

PMID- 11976779
TI  - Doppler echocardiography.
AB  - We describe concepts important in the clinical application of continuous wave,
      pulsed wave, and color Doppler flow imaging. In the second half of this
      manuscript, the application of these tools in pediatric echocardiography is
      addressed.

PMID- 11976780
TI  - Fetal echocardiography: new grounds to explore during fetal cardiac intervention.
AB  - Over the past decade, revolutionary advances in ultrasound imaging technology
      have allowed the study of the evolution of congenital heart disease during fetal
      life. The frustration arising from watching the prenatal progression of severe
      semilunar valve obstructions and therapy-refractory fetal arrhythmias has
      prompted the interest in developing procedures for fetal cardiac intervention.
      Ultrasound techniques as the primary diagnostic and monitoring modalities in
      fetal medicine will play a key role in defining patient groups, peri
      interventional assessment of fetal hemodynamics, and monitoring during these
      procedures. The purpose of this article is to provide pediatric cardiologists and
      perinatal medicine specialists an overview over the various technical approaches
      at fetal cardiac intervention and the special tasks that fetal echocardiography
      will have to accomplish. It also aims at illustrating the potential of fetal
      echocardiography for fetal selection.

PMID- 11976781
TI  - Pediatric stress echocardiography.
AB  - Traditional health evaluations are performed while the patient is at rest. Stress
      echocardiography extends these examinations by providing data in a physiologic
      setting more closely mimicking the typically active state of children. The test
      represents a fusion of the fields of two-dimensional echocardiography and
      cardiovascular stress testing and can be used to assess myocardial perfusion in
      patients with suspected coronary artery pathology or to evaluate cardiac
      gradients or functional reserve in patients with noncoronary artery pathology.
      Testing should be performed with a trained sonographer and attending physician
      and in collaboration with adult cardiology colleagues. Stress can be administered
      to the patient through either exercise or pharmacologic agents. Echocardiography
      is used to assess regional wall motion abnormalities when evaluating myocardial
      perfusion or gradients and/or function when assessing the patient without
      coronary artery issues. Conditions with potential coronary artery pathology for
      which stress echocardiography is appropriate include Kawasaki disease, transplant
      graft vasculopathy, arterial switch operation for transposition of the great
      arteries, anomalous coronary artery origins or courses, pulmonary atresia with
      intact ventricular septum, hyperlipidemia, insulin-dependent diabetes mellitus,
      and supravalvar aortic stenosis. Stress echocardiography can also be helpful in
      determining the behavior during activity of gradients in conditions such as
      hypertrophic cardiomyopathy or aortic and pulmonic stenosis, of cardiac pressures
      in pulmonary hypertension and of ventricular function in conditions such as
      dilated cardiomyopathy or mitral and aortic regurgitation.

PMID- 11976782
TI  - Digital echocardiography and telemedicine applications in pediatric cardiology.
AB  - Digital echocardiography offers several advantages over videotape, including easy
      review, comparison, storage, postprocessing, and sharing of studies, quantitative
      analysis, and superior resolution. Newer echocardiography systems can write
      digital data to computer hardware, whereas older systems require digitization of
      analog data. Clinical and digital data compression is required to reduce study
      size. Clinical compression has been validated in several adult studies and one
      pediatric study. JPEG and MPEG digital compression ratios of 26:1 and 200:1,
      respectively, approximate S-videotape quality. JPEG is the DICOM 3.0 standard and
      is ideal for short loops, serial comparisons, and quantitative analysis. MPEG
      (the motion picture standard) lends itself to digitization of video streams and
      may be more attractive to pediatric cardiologists. Options for data storage and
      transfer range from limited local review to multiple offline review stations
      linked by a wide-area network. Telemedicine expands the capabilities of digital
      echocardiography in a "store and forward" or "real-time" format. Real-time
      neonatal telecardiology is accurate, impacts patient care, is cost-effective, and
      does not increase utilization. Cost, increased reliance on sonographers' skills,
      lack of accepted standards, and legal, licensure, and billing issues are
      obstacles to widespread acceptance of digital echocardiography and telemedicine.

PMID- 11976785
TI  - The diversity and function of soil microbial communities exposed to different
      disturbances.
AB  - To improve understanding of the relationship between the diversity and function
      of the soil ecosystem, we investigated the effect of two different disturbances
      on soil bacterial communities -- long-term exposure to the heavy metal mercury
      and transient exposure to the antibiotic tylosin. In the mercury-contaminated
      soil the diversity (Shannon index) was reduced as assessed from denaturing
      gradient gel electrophoresis (DGGE) of amplified 16S rDNA sequences from the soil
      community DNA and from colony morphology typing of the culturable bacterial
      population. However, analysis of the substrate utilization profiles did not
      reveal any differences in diversity. In the tylosin-treated soil, DGGE revealed a
      small difference in the diversity of 16S rDNA compared to the control soil,
      whereas analysis of the colony morphology typing or substrate utilization results
      did not reveal any differences in diversity. Soil function was also affected by
      mercury contamination. The lag time before soil respiration increased following
      addition of glucose or alfalfa substrate was longer in the mercury-contaminated
      soil than in the control soil. Moreover, it was markedly prolonged in mercury
      contaminated soil subjected to heat treatment prior to substrate addition, thus
      indicating reduced resistance to a new disturbance in the mercury-contaminated
      soil as compared to the control soil. Tylosin treatment did not have any
      significant effect on any of the respiration parameters measured, either with or
      without prior heat treatment of the soil.

PMID- 11976788
TI  - Molecular cloning, characterization, and quantification of squirrel monkey (
      Saimiri sciureus) Th1 and Th2 cytokines.
AB  - Primates have long been used as models to study the basic mechanisms of human
      disease. The squirrel monkey, Saimiri sciureus,is a New World monkey that can be
      satisfactorily bred in captivity and infected with various human pathogens. The
      basic immunological parameters of squirrel monkeys, including immunoglobulin
      subclasses and markers for lymphocyte subsets, have already been characterized.
      However, immunological reagents and assays specific for the detection and
      quantification of squirrel monkey cytokines are required to elucidate the
      immunological and physiopathological changes that occur during experimental
      infection of these animals with pathogens. We therefore cloned, sequenced, and
      characterized the cDNAs encoding various squirrel monkey Th1 and Th2 cytokines,
      including interleukin (IL)-1 beta, IL-2, IL-5, IL-6, IL-10, tumor necrosis factor
      alpha, and gamma interferon. We found 91.4%-98.1% homology between the nucleotide
      sequence of the squirrel monkey cytokine genes and published sequences of
      equivalent human and non-human primate genes. The aligned sequences of cytokines
      for Saimiriand several New and Old World primates and human are shown, and a
      phylogenetic analysis of published sequences of selected cytokines in other
      species and those of non-human primates is given. In addition, we adapted a
      previously described quantitative, reverse transcriptase, competitive polymerase
      chain reaction technique to measure the mRNA expression of those cytokines in
      squirrel monkeys. The primer and competitor plasmids that allowed quantification
      are described. We showed that the assay is sensitive and reproducible.

PMID- 11976786
TI  - A polymorphism in the human cytotoxic T-lymphocyte antigen 4 ( CTLA4) gene (exon
      1 +49) alters T-cell activation.
AB  - The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an important modifier of T-cell
      activation with down-regulatory properties upon B7 engagement. An allelic
      polymorphism in exon 1 of the CTLA4 gene coding for the peptide leader sequence
      of CTLA4 was recently described. This polymorphism was detected in association
      with several autoimmune diseases. In this study, we investigated the functional
      impact of the CTLA4 exon 1 +49 A/G dimorphism on T-cell activation and cellular
      localization. We examined the T-cell response from healthy donors either
      homozygous for A or G at position +49 of the exon 1. Under suboptimal stimulation
      conditions we found a greater proliferative response of cells from donors
      homozygous for G at position +49. FACS analysis of CTLA4 expression revealed a
      reduced up-regulation of CTLA4 from G/G donors upon T-cell activation, if
      compared with wild-type cells. Intracellular CTLA4 distribution demonstrated
      qualitatively different staining patterns between the two genotypes as determined
      using confocal fluorescence microscopy. Our results suggest that the G allele at
      position +49 of exon 1 affects the CTLA4-driven down-regulation of T-cell
      activation and may be an important factor in the pathogenesis of autoimmune
      diseases.

PMID- 11976787
TI  - Evolutionary relationships and polymorphisms among V kappa 10 genes from inbred
      and wild-derived inbred mice.
AB  - The V kappa 10 family in BALB/c mice is composed of three members, two of which
      are utilized in a variety of immune responses. We previously demonstrated that
      the product of the third gene, V kappa 10C, has never been detected as part of a
      functional antibody and productive rearrangements are selectively lost during B
      cell development. Here we analyzed germline V kappa 10 genes from inbred and wild
      derived mice by RFLP and sequencing in order to determine the origin of the V
      kappa 10C gene, as well as to examine the evolutionary relationships of V kappa
      10 genes. Our results demonstrated that the V kappa 10 family is highly conserved
      across Mus species and subspecies, but that V kappa 10C is rare, being found in
      only inbred mice of V kappa 10 allelic group b and two of six M. m. domesticus
      isolates. It was not found in other M. musculus subspecies or M. spretus. V kappa
      10A and V kappa 10B were found in all strains, with the exception of one M. m.
      domesticus isolate, which had only V kappa 10B genes. Overall, V kappa 10A
      sequences were more highly conserved than V kappa 10B, indicating that different
      selective pressures may be operating on these genes. The two V kappa 10C
      sequences from M. m. domesticus were 100% identical to that found in inbred mice.
      V kappa 10C is more closely related to V kappa 10B than to V kappa 10A and our
      data suggest that it is a recent duplication of the V kappa 10B gene.

PMID- 11976790
TI  - Heavy-chain antibodies in Camelidae; a case of evolutionary innovation.
AB  - The emergence in Camelidae species of functional antibodies devoid of light
      chains (referred to as heavy-chain antibodies or HCAbs) is an intriguing
      evolutionary event. Homodimeric HCAbs have also been documented in spotted
      ratfish ( Cos5-Abs) and nurse shark (NAR). To reveal the evolutionary history of
      HCAbs, we evaluated the phylogenetic and phenotypic relationships among HCAbs and
      conventional antibodies across taxa and confirmed the current viewpoint that
      different groups of HCAbs have evolved independently in the three lineages. At
      least, in the camelids, HCAbs are not the result of resuscitation of dormant
      genes. They are derived from the conventional antibodies within the Camelidae
      lineage, and are apparently the outcome of more recent adaptive changes occurring
      in the compartment of heteromeric antibodies. The shared structural properties of
      HCAbs across taxa are therefore explained by convergent evolution due to similar
      constraints related to the absence of pairing to the light chain. It appears that
      innovative evolutionary changes in Camelidae have led to a new level of antigen
      binding repertoire diversification and have allowed acquisition of novel antigen
      receptor properties.

PMID- 11976789
TI  - Molecular cloning, sequencing, and characterization of bovine transporter
      associated with antigen processing 2 ( BoTAP2).
AB  - The transporter associated with antigen processing (TAP) 1/2 heterodimer is
      essential for the transport of antigenic peptides from the cytosol into the lumen
      of the endoplasmic reticulum. Bovine herpesvirus 1 (BHV-1) inhibits bovine TAP
      (BoTAP) activity, as a means of down-regulating MHC class I expression on the
      cell surface, and hence evasion of the cytotoxic T-lymphocyte response of the
      host. Identification of BHV-1 protein(s) responsible for TAP inhibition, and
      elucidation of the mechanism of TAP inhibition necessitate cloning and high-level
      expression of BoTAP1 and 2. In this study, we cloned and sequenced BoTAP2.
      Cytoplasmic RNA isolated from bovine peripheral blood mononuclear cells was used
      for cDNA synthesis. Rapid amplification of cDNA ends was used to amplify the 5'
      and the 3' ends of BoTAP2 cDNA. Based on the 5' and 3' sequences, primers were
      designed and the full-length BoTAP2 cDNA was PCR-amplified and sequenced. The
      full-length cDNA encodes a 719-amino acid polypeptide with a predicted molecular
      weight of M(r) 79,000. BoTAP2 has approximately 80% homology, at the amino acid
      level, to its mammalian counterparts. Similar to human TAP2, BoTAP2 consists of
      seven putative transmembrane segments followed by an ATP-binding cassette. As
      expected, the level of BoTAP2 mRNA expression was up-regulated by treatment with
      recombinant bovine interferon-gamma. In Northern blot analysis, BoTAP2
      transcripts were detected in several bovine tissues with the highest level
      observed in jejunum. BoTAP2, when expressed as a green fluorescent fusion
      protein, exhibited a typical endoplasmic reticulum localization pattern.

PMID- 11976791
TI  - Histocompatibility reaction in tissue and cells of the marine sponge Suberites
      domuncula in vitro and in vivo: central role of the allograft inflammatory factor
      1.
AB  - Sponges (Porifera) are the phylogenetically oldest still extant metazoan phylum.
      Recently elements of their immune system have been cloned and analyzed, primarily
      from the demosponges Suberites domuncula and Geodia cydonium. By differential
      display, two genes were identified in S. domuncula, whose translation products
      are involved in graft rejection/fusion: the allograft inflammatory factor (AIF-1)
      and the Tcf-like transcription factor (TCF). Since the AIF-1 and TCF genes are
      upregulated in vivo after tissue transplantation, especially in allografts, we
      investigated whether this reaction can be monitored in vitro. Therefore, the
      autogeneic and the allogeneic mixed sponge cell reaction (MSCR) system was
      applied for the first time to identify distinct factors in sponges in vitro. The
      results confirm that the two AIF-1 and TCF genes are induced during allogeneic
      MSCR. Furthermore, the recombinant sponge AIF-1 causes an upregulation of the
      expression of the TCF. We conclude that the AIF-1 and TCF genes are upregulated
      in sponges during histoincompatibility reactions; the data support the view that
      sponges have immune systems composed of highly complex elements related to those
      found in mammalian systems.

PMID- 11976792
TI  - CARD15 gene and the classification of Crohn's disease.
AB  - An insertion mutation at nucleotide 3020 (3020insC) in the CARD15 gene,
      originally reported as NOD2, has been strongly associated with Crohn's disease.
      The CARD15 G2722C missense mutation was also shown to be associated with this
      disease. We studied 130 Dutch Crohn's disease patients, with a median follow up
      of 9.2 years, in relation to the Vienna classification, and 152 ethnically
      matched healthy controls. We confirm reports that the CARD15 3020insC mutation
      increases the susceptibility to Crohn's disease, but we do not confirm this
      relationship for CARD15 G2722C. Our findings suggest that these mutations are not
      a marker of a particular form of Crohn's disease according to the Vienna
      classification. Whether the CARD153020insC and CARD15 G2722C mutations are
      responsible for a different etiopathogenic mechanism in a subgroup of patients
      remains to be studied.

PMID- 11976793
TI  - Physical map of the mouse lambda light chain and related loci.
AB  - The lambda light chain genes and the related loci lambda 5, V(preB)1 and V(preB)2
      are selectively expressed in the development of B lymphocytes. The sequences and
      the order of the gene segments are known, but a precise physical map of the
      lambda locus has not yet been published. Using the Celera mouse genome database
      we constructed such a map. In this paper, we confirm the order of the gene
      segments as being V lambda 2 - V lambda X - J lambda 2 - C lambda 2 - J lambda 4 
      C lambda 4 - V lambda 1 - J lambda 3 - C lambda 3 - J lambda 1 - C lambda 1 and
      give precise germ line distances. We located the V(preB)2 locus 3' to the lambda
      locus, 1,077,001 bp downstream; the V(preB)1 locus, 2,180,618 bp downstream of
      the lambda locus; and the lambda 5 gene, 4,667 bp downstream of the V(preB)1
      locus. Except for the V(preB)2 locus all other loci are in the same
      transcriptional orientation.

PMID- 11976794
TI  - Is there a role for lymphoscintigraphy and sentinel node biopsy in the management
      of the regional lymphatics in mucosal squamous cell carcinoma of the head and
      neck?

PMID- 11976795
TI  - Electron beam computed tomography and ventilation perfusion scintigraphy in the
      diagnosis of pulmonary embolism.
AB  - The purpose of this study, performed in patients with suspected pulmonary
      embolism (PE), was to compare V/Q scans and electron beam computed tomography
      (CT) scans on a patient-by-patient and segment-by-segment basis. Both a segment
      based and a lobe-based analysis was performed in those patients positive for PE.
      The diagnosis of PE was assumed on the basis of a mismatch at V/Q scanning or a
      filling defect in a pulmonary vessel at contrast-enhanced electron beam CT. In
      37/45 patients (24 female, 21 male, 58+/-16 years) with suspected PE, the
      diagnosis of PE was confirmed or excluded by both modalities, resulting in a
      correlation of 82% between electron beam CT and V/Q scanning. In the 28 patients
      positive for PE according to one or both modalities, 504 segments were evaluated.
      Of these 504 segments, 248 (nearly 50%) showed perfusion defects on V/Q scans, of
      which only 90 (36%) displayed emboli at electron beam CT. Overall, a total of
      only 135 of the 504 segments (27%) were abnormal at electron beam CT. More than
      50% of the patients with discrepant results did not show an embolus at electron
      beam CT. It is concluded that there is a good correlation (82%) between V/Q
      scanning and electron beam CT on a patient-by-patient basis but a markedly less
      good correlation (62%) in a segment-based analysis.

PMID- 11976796
TI  - Bone marrow immunoscintigraphy using technetium-99m anti-granulocyte antibody in
      multiple myeloma.
AB  - Conventional skeletal radiography and bone scan have certain limitations in the
      initial evaluation of bone and bone marrow lesions in multiple myeloma (MM). In
      this study we investigated the value of bone marrow immunoscintigraphy (BMIS)
      using anti-granulocyte monoclonal antibody (AGA) for the diagnosis of bone
      involvement of MM, in comparison with bone scan and skeletal radiography. Whole
      body BMIS using technetium-99m-labelled AGA was performed in 22 MM patients (15
      male, 7 female) and the imaging findings compared with those of skeletal
      radiography and (99m)Tc-methylene diphosphonate bone scan. The findings of bone
      marrow aspiration and serum biochemical findings were also compared with BMIS
      findings. Abnormal findings of BMIS were defined as presence of a focal photon
      defect in the axial skeleton or expansion of peripheral bone marrow. A total of
      124 focal lesions were detected in 19 subjects (86%) by skeletal radiography,
      bone scan or BMIS. BMIS detected 92 lesions (74%) in 19 subjects, whereas
      skeletal radiography detected 58 focal lesions (47%) in 14 and bone scan 40
      lesions (32%) in 11. Fifty-one (41%) of the 124 lesions were only seen on BMIS.
      Spine and pelvic lesions were better visualised by BMIS, whereas skull lesions
      were better seen with skeletal radiography, and bone scan detected more lesions
      in the ribs. Marrow expansion was noted in 15 subjects (68%) on BMIS, and its
      grade correlated with marrow cellularity and myeloma cell percentage in bone
      marrow aspirates ( P=0.0055 and P=0.0541, respectively). BMIS revealed abnormal
      lesions in one of three stage II patients and 17 out of 19 stage III patients.
      The number of lesions of the thoracolumbar vertebrae on BMIS was correlated with
      cellularity ( P=0.0393), but not with myeloma cell percentage ( P=0.1262). These
      findings suggest that the results of BMIS with (99m)Tc-labelled AGA correlate
      with clinical stage, and thus reflect the functional status of bone marrow in MM
      patients. BMIS might be useful for the detection of bone involvement of MM when
      skeletal radiography or bone scan is inconclusive, especially for vertebral
      lesions.

PMID- 11976797
TI  - Use of the incretin hormone glucagon-like peptide-1 (GLP-1) for the detection of
      insulinomas: initial experimental results.
AB  - The non-invasive detection of insulinomas remains a diagnostic problem that is
      not solved by means of somatostatin receptor scintigraphy. We investigated the
      biokinetics and specificity of uptake and degradation of the incretin hormone
      glucagon-like peptide-1 (GLP-1) in a rat insulinoma cell line (RINm5F) in order
      to ascertain whether radiolabelled GLP-1 may be suitable for specific
      visualisation of insulinomas in vivo. GLP-1 (7-36)amide was radioiodinated
      according to the iodogen method. The specificity of the uptake of [(125)I]GLP-1(7
      36)amide by RINm5F cells was investigated. Degradation products of GLP-1 (7
      36)amide in the cell medium were purified by HPLC. Their masses and amino acid
      sequences were determined by (252)Cf-plasma desorption mass spectrometry.
      Lysosomal degradation was inhibited and after differential centrifugation the
      amount of radiotracer incorporated into lysosomes was determined. Biodistribution
      studies were performed in a rat insulinoma model (NEDH rats and RINm5F cells)
      with [(123)I]GLP-1(7-36)amide and its more stable agonist [(123)I]exendin 3. The
      uptake of radiotracer into insulinoma cells reached a maximum within 5 min. It
      was inhibited by an excess of unlabelled peptide. [(125)I]GLP-1(7-36)amide
      accumulated in the cells if lysosomal degradation was inhibited. Degradation
      products of the peptide were found in the cell medium. We determined their mass
      and derived their amino acid sequence. Radiolabelling of exendin 3 was more
      difficult than that of GLP-1 because of the lack of tyrosine in its primary
      structure. Biodistribution studies showed rapid blood clearance and uptake of the
      radiotracer into the tumour and the pancreas. It was also possible to detect
      insulinomas in an animal model by external scintigraphy using radioiodinated GLP
      1 (7-36)amide and exendin 3. GLP-1 (7-36)amide is specifically internalised into
      insulinoma cells by a receptor-mediated mechanism. Our results demonstrate that
      GLP-1 receptor-directed scintigraphy may be a new method for the detection of
      insulinomas in vivo. Due to the short half-life of GLP-1, its more stable
      analogue exendin 3 may better suit this purpose in vivo.

PMID- 11976799
TI  - A comparison of (99m)Tc-HMPAO SPET changes in dementia with Lewy bodies and
      Alzheimer's disease using statistical parametric mapping.
AB  - Differences in regional cerebral blood flow (rCBF) between subjects with
      Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and healthy volunteers
      were investigated using statistical parametric mapping (SPM99). Forty-eight AD,
      23 DLB and 20 age-matched control subjects participated. Technetium-99m
      hexamethylpropylene amine oxime (HMPAO) brain single-photon emission tomography
      (SPET) scans were acquired for each subject using a single-headed rotating gamma
      camera (IGE CamStar XR/T). The SPET images were spatially normalised and group
      comparison was performed by SPM99. In addition, covariate analysis was undertaken
      on the standardised images taking the Mini Mental State Examination (MMSE) scores
      as a variable. Applying a height threshold of P < or = 0.001 uncorrected,
      significant perfusion deficits in the parietal and frontal regions of the brain
      were observed in both AD and DLB groups compared with the control subjects. In
      addition, significant temporoparietal perfusion deficits were identified in the
      AD subjects, whereas the DLB patients had deficits in the occipital region.
      Comparison of dementia groups (height threshold of P < or = 0.01 uncorrected)
      yielded hypoperfusion in both the parietal [Brodmann area (BA) 7] and occipital
      (BA 17, 18) regions of the brain in DLB compared with AD. Abnormalities in these
      areas, which included visual cortex and several areas involved in higher visual
      processing and visuospatial function, may be important in understanding the
      visual hallucinations and visuospatial deficits which are characteristic of DLB.
      Covariate analysis indicated group differences between AD and DLB in terms of a
      positive correlation between cognitive test score and temporoparietal blood flow.
      In conclusion, we found evidence of frontal and parietal hypoperfusion in both AD
      and DLB, while temporal perfusion deficits were observed exclusively in AD and
      parieto-occipital deficits in DLB.

PMID- 11976798
TI  - The usefulness of repeated ictal SPET for the localization of epileptogenic zones
      in intractable epilepsy.
AB  - This study investigated whether repeated ictal single-photon emission tomography
      (SPET) is helpful in the localization of epileptogenic zones and whether it can
      provide information confirming that an area of increased perfusion is really the
      culprit epileptogenic lesion. Fifty-four repeated ictal SPET studies were
      performed in 24 patients with ambiguous or unexpected findings on the first ictal
      SPET study. These patients were enrolled from among 502 patients with intractable
      epilepsy in whom pre-operative localization of epileptogenic zones was attempted
      with a view to possible surgical resection. Video monitoring of ictal behaviour
      and EEGs was performed in all patients. Repeated ictal SPET was performed using
      technetium-99m hexamethylpropylene amine oxime (HMPAO) when there was no
      prominently hyperperfused area or when unexpected findings were obtained during
      the first study. Two ictal SPET studies were performed in 19 patients, three
      studies in four patients and four studies in one patient. The average delay
      between ictal onset and injection was 28 s for the first study and 22 s for the
      second, third and fourth studies. Using interictal SPET, ictal-interictal
      subtraction images were acquired and co-registered with the population magnetic
      resonance imaging (MRI) template. Invasive study and surgery were performed in 18
      patients, and in these cases the surgical outcome was known. In the other six
      patients, epileptogenic foci were determined using MRI, positron emission
      tomography (PET) and ictal EEG findings. Two patients were found to have mesial
      temporal lobe epilepsy, two lateral temporal lobe epilepsy, eight frontal lobe
      epilepsy, three parietal lobe epilepsy and one occipital lobe epilepsy. The other
      eight had multifocal epilepsy. The first study was normal in 12 patients (group
      I) and indicated certain zones to be epileptogenic in the other 12 (group II).
      Among group I, the correct epileptogenic zone or lateralization was revealed at
      the repeated study in nine patients, while in the other three it was not. Among
      group II, six patients showed the same results at the second study, thus
      confirming that the initially identified zones were of epileptogenic
      significance. In the other six patients, different areas were identified on the
      first and second studies, and repeated ictal SPET corroborated multifocality of
      the ictal EEG findings in five. These results indicate that repeated ictal SPET
      is useful because it can yield new or additional information about the
      epileptogenic zones and can confirm that a region of interest is an epileptogenic
      zone or that the epilepsy is of multifocal origin.

PMID- 11976801
TI  - Potential significance of (11)C-methionine PET as a marker for the
      radiosensitivity of low-grade gliomas.
AB  - The role for radiotherapy in patients with low-grade gliomas remains
      controversial. Two large prospective studies have failed to demonstrate a
      radiotherapeutic dose-response effect, and EORTC trial 22845 found no difference
      in survival between patients receiving adjuvant radiotherapy and those who
      received radiotherapy at tumour progression. The aim of this retrospective study
      was to analyse the patterns of carbon-11 methionine (MET) uptake on positron
      emission tomography (PET) in tumours treated with immediate radiotherapy and in
      those treated with delayed radiotherapy at the time of tumour progression. The 21
      adult patients studied had histologically confirmed low-grade gliomas and had
      undergone a pre-treatment PET scan and a follow-up PET scan at the time of
      progression. Eleven of the patients had undergone initial radiotherapy a median
      of 5 weeks after the surgical procedure. The median time to progression was 3.5
      years for this group, compared with 1.6 years for the group with delayed
      radiotherapy ( P=0.06). At the time of progression, non-irradiated tumours had a
      significantly higher MET uptake ( P=0.02) and a larger uptake volume ( P=0.008)
      compared with baseline, whereas irradiated tumours showed no statistically
      significant change. We observed a correlation between high pre-treatment uptake
      of MET and reduction in MET uptake in response to radiotherapy ( P=0.008). All
      irradiated tumours recurred within the radiation field. In conclusion, our
      results demonstrate signs of a residual radiation effect at the time of tumour
      progression in low-grade gliomas with high pre-treatment uptake of MET. Pre
      treatment methionine uptake may be a marker for the radiosensitivity of low-grade
      gliomas.

PMID- 11976800
TI  - Quantification of [(123)I]PE2I binding to dopamine transporters with SPET.
AB  - The iodinated cocaine derivative [(123)I]PE2I is a new selective ligand for in
      vivo studies of the dopamine transporter (DAT) with single-photon emission
      tomography (SPET). The aim of the present study was to describe a method for
      accurate quantification of binding data following a bolus injection of
      [(123)I]PE2I. Six healthy subjects (age 51+/-24 years) underwent xenon-133 SPET
      for quantification of regional CBF and [(123)I]PE2I SPET for quantification of
      DAT binding. rCBFs were within normal limits in all subjects. Fitting data to a
      two-tissue compartment model resulted in striatal K(1) values of 0.39+/-0.08 ml
      ml(-1) min(-1), equal to a first-pass extraction fraction of 0.72+/-0.13.
      Distribution volumes (DVs) were calculated using compartment analysis, area under
      the curve analysis and Logan analysis. Logan analysis is preferred since stable
      DV values were already obtained 120 min after [(123)I]PE2I injection. Mean
      striatal DV was 37.9+/-9.6 ml ml(-1) and mean occipital cortex DV was 5.5+/-0.7
      ml ml(-1). In the absence of local pathology in a reference tissue, Logan
      analysis without blood sampling is an attractive method for accurate
      quantification of striatal [(123)I]PE2I binding. The distribution volume ratio
      (DVR) (6.6+/-1.4) was in good agreement with the DVR calculated with blood (6.7+/
      1.4).

PMID- 11976802
TI  - Influence of rhTSH on [(18)F]fluorodeoxyglucose uptake by differentiated thyroid
      carcinoma.
AB  - The influence of serum TSH levels on fluorine-18 fluorodeoxyglucose (FDG) uptake
      by recurrences or metastases of differentiated thyroid carcinomas has not yet
      been clarified. The aim of this study was to ascertain whether the administration
      of recombinant human thyrotropin (rhTSH) stimulates FDG uptake by such lesions.
      In this prospective study, 30 patients with positive or equivocal thyroglobulin
      (Tg) levels and negative or equivocal iodine-131 and/or morphological imaging
      results (ultrasound, MRI, CT) underwent FDG positron emission tomography (PET)
      under exogenous TSH suppression and under exogenous TSH stimulation of serum
      levels by injection of rhTSH. The mean interval between the FDG-PET studies under
      these two conditions was 9.3+/-8.8 weeks. Serum TSH levels and free thyroid
      hormones were determined on each occasion. FDG uptake was quantitated using
      tumour to background ratios (TBRs) and standardised uptake values (SUVs). Under
      TSH suppression there was focal FDG accumulation in nine subjects (22 tumour-like
      lesions). The total number of foci was 45. After exogenous TSH stimulation, the
      number of patients in whom FDG foci were detected was 19, and the number of foci
      identified was 82 (78 tumour-like lesions). TBR of regions showing positive FDG
      contrast with either of the modalities averaged 2.54+/-1.89, and under stimulated
      TSH levels, 5.51+/-2.99 ( P<0.0001). Corresponding SUVs were 2.05+/-1.45 versus
      2.77+/-1.58 ( P<0.001). In a small number ( n=4) of foci related to inflammatory
      lymph nodes, TBR and SUV were only marginally increased under TSH stimulation
      (2.01+/-0.38 and 1.07+/-0.38, respectively), and the values did not differ
      significantly from those obtained under suppression. These results provide the
      first direct evidence that TSH stimulates FDG uptake by differentiated thyroid
      carcinoma and that, therefore, FDG-PET is more accurate under rhTSH than under
      suppression.

PMID- 11976804
TI  - Comparative microvascular exchange kinetics of [(77)Br]bromide and (99m)Tc-DTPA
      in humans.
AB  - The plasma clearance curves of small hydrophilic solutes comprise three
      exponentials, consistent with a three-compartmental distribution model. A
      previous comparison between inulin and diethylene triamine penta-acetic acid
      (DTPA) suggested that these three compartments are in series, the first being
      plasma and the second and third representing compartments within the
      extravascular space. Moreover, whilst the total distribution volumes of these two
      indicators were similar, the volume of the second compartment was higher for
      DTPA. The purpose of the current study was to investigate whether a solute
      smaller than DTPA, namely bromide, fits the hypothesis that the second space
      volume is an inverse function of the size of the solute. Two groups of subjects
      were studied: group A comprised eight patients undergoing routine diagnostic
      arteriography and group B, eight patients referred for routine measurement of
      glomerular filtration rate plus two normal volunteers. (99m)Tc-DTPA and sodium
      [(77)Br]bromide were intravenously administered simultaneously. In group A,
      frequent arterial samples were obtained up to 40 min after injection, and
      antecubital venous samples 30 s after each arterial sample. In group B, frequent
      venous samples were obtained up to 280 min after injection. Volume measurements
      based on bromide were corrected for erythrocyte bromide accumulation. In both
      subject groups, the normalised venous concentration ratio of bromide to DTPA,
      corrected for red cell bromide uptake, was significantly less than unity in the
      earliest blood samples, being 0.56 (SD 0.08) at 1 min, consistent with faster
      diffusion of bromide from plasma to interstitial fluid. Furthermore, the
      extraction fraction of bromide from plasma to interstitial fluid in the forearm
      was about 0.6, higher than that of DTPA (about 0.5) in spite of red cell bromide
      accumulation which equilibrated with plasma bromide within 20 s and resulted in a
      red cell to plasma concentration ratio of 0.51 (0.09). Nevertheless, the net
      extraction fractions of the two solutes approached asymptotic values with
      identical time courses over 20-25 min. The total volume of distribution of
      bromide in group B was 22.5 (3.8) litres, which was higher than that of DTPA,
      18.0 (2.8) litres ( P<0.001). It was assumed that this difference was the result
      of intracellular bromide accumulation. After correction for this, the combined
      volume of the first and second spaces was significantly higher for bromide, at
      13.9 (2.9) litres, than for DTPA, 12.3 (2.0) litres ( P<0.05), but the volume of
      the third space, 4.1 (2.8) litres, was less compared with DTPA, for which it was
      5.8 (2.2) litres ( P<0.05). The proportion of the total space occupied by the
      first and second spaces was also higher for bromide, 0.78 (0.14), than for DTPA,
      for which it was 0.69 (0.09; P<0.05). These data are consistent with a three-in
      series-compartmental model of solute distribution in which the volume of the
      second space is an inverse function of solute molecular size while the volume of
      the third is a positive function of solute size.

PMID- 11976803
TI  - (18)F-FDG and (18)F-FET uptake in experimental soft tissue infection.
AB  - The aim of this study was to compare the uptake of (18)F-fluoroethyl- L-tyrosine
      ((18)F-FET) with that of (18)F-fluorodeoxyglucose ((18)F-FDG) in activated
      inflammatory white blood cells. Unilateral thigh muscle abscesses were induced in
      11 rats by intramuscular inoculation of 0.1 ml of a bacterial suspension ( S.
      aureus, 1.2 x 10(9) CFU/ml). Four animals were intraperitoneally injected with
      130-180 MBq (18)F-FDG, four with 140-170 MBq (18)F-FET and three with a mixture
      of 140-170 MBq (18)F-FET and 1.8 MBq (14)C-deoxyglucose. Autoradiography (10
      microm slice thickness) of the abscess and the contralateral muscle was performed
      and detailed spatial correlation of autoradiography and histopathology
      (haematoxylin-eosin staining) was obtained. Regions of interest were placed on
      the abscess wall and the grey values (digitised image intensities) measured were
      converted to kBq/cc per kBq injected activity per gram (SUV). Areas with
      increased (18)F-FDG uptake corresponded to cellular inflammatory infiltrates
      mainly consisting of granulocytes. The SUV was calculated to be 4.08+/-0.65
      (mean+/-SD). The uptake of (18)F-FET in activated white blood cells was not
      increased: the SUV of the abscess wall, at 0.74+/-0.14, was even below that of
      contralateral muscle. The low uptake of (18)F-FET in non-neoplastic inflammatory
      cells promises a higher specificity for the detection of tumour cells than is
      achieved with (18)F-FDG, since the immunological host response will not be
      labelled and inflammation can be excluded.

PMID- 11976806
TI  - Feasibility of sentinel node lymphoscintigraphy in stage I testicular cancer.
AB  - The aim of this study was to investigate the feasibility of lymphoscintigraphy
      for sentinel node identification in testicular cancer. Five patients with
      clinical stage I testicular cancer were prospectively included. A single dose of
      technetium-99m nanocolloid (mean dose 99 MBq, volume 0.2 ml) was injected into
      the funiculus in the first patient and into the testicular parenchyma in the
      following four patients. Dynamic lymphoscintigraphy was performed over 10 min,
      followed by early and late static images after 15 min and 2 to 24 h,
      respectively. Lymphoscintigraphy was followed by laparoscopic sentinel node
      biopsy on the same day in the last two patients using patent blue dye and an
      endoscopic gamma probe. The funicular administration route showed five hot spots
      in the right inguinal region after 2 h. Intratesticular administration resulted
      in sentinel node visualisation in three of the four patients. Dynamic images
      showed afferent lymphatic vessels to one sentinel node in the left para-aortic
      region in two patients and two sentinel nodes in the left para-aortic region in
      another patient. Sentinel nodes were intraoperatively identified in one of two
      patients who underwent laparoscopic exploration. It is concluded that
      lymphoscintigraphy for sentinel node identification is feasible in stage I
      testicular cancer using intratesticular radiocolloid administration.

PMID- 11976805
TI  - Use of arterialised venous instead of arterial blood for measurement of
      myocardial glucose metabolism during euglycaemic-hyperinsulinaemic clamping.
AB  - Sampling of arterialised venous blood (AVB) is often used as an alternative to
      sampling of arterial blood when determining the myocardial metabolic rate of
      glucose (MRGlu). This method, however, has not yet been validated for measurement
      of plasma fluorine-18 fluorodeoxyglucose (FDG) activity during a euglycaemic
      hyperinsulinaemic clamp (EHC). In this study, dynamic FDG scans were performed
      with arterial blood sampling during EHC. Samples of arterial and AVB or venous
      blood were simultaneously withdrawn at five time points for measurement of FDG
      activity and plasma glucose in 36 patients. Both venous to arterial and AVB to
      arterial ratios were calculated for FDG activity and plasma glucose. Mean ratios
      between AVB and arterial FDG activity were then used to create calculated
      arterialised venous input functions from corresponding arterial input functions.
      The mean effect of arterialisation on the calculation of K(i) was assessed. In
      nine additional patients, K(i) obtained with continuous sampling of AVB was
      compared with K(i) obtained with a corresponding (quality-controlled) image
      derived input function from the ascending aorta. Using AVB, measurements of FDG
      activity were much more reliable than with venous blood sampling. As compared
      with arterial sampling, however, FDG activity was underestimated early after
      injection, while it was overestimated after 20 min. In both analyses, AVB
      resulted in approximately 10%+/-10% overestimation of K(i). Because of a 5%+/-5%
      underestimation of plasma glucose concentration with AVB, the net effect on the
      final calculation of MRGlu was small (on average 5% overestimation). It is
      concluded that the use of AVB has a small average effect on the determination of
      MRGlu. This method does, however, contribute to variability in the results. This
      variability cannot be explained by different degrees of arterialisation.

PMID- 11976807
TI  - Technetium-99m labelled fluconazole and antimicrobial peptides for imaging of
      Candida albicans and Aspergillus fumigatus infections.
AB  - The aim of this study was to investigate whether technetium-99m labelled
      fluconazole can distinguish fungal from bacterial infections. Fluconazole was
      labelled with (99m)Tc and radiochemical analysis showed less than 5% impurities.
      The labelling solution was injected into animals with experimental infections.
      For comparison, we used two peptides for infection detection, i.e. UBI 29-41 and
      hLF 1-11, and human IgG, all labelled with (99m)Tc. Mice were infected with
      Candida albicans or injected with heat-killed C. albicans or lipopolysaccharides
      to induce sterile inflammation. Also, mice were infected with Staphylococcus
      aureus or Klebsiella pneumoniae. Next, accumulation of (99m)Tc-fluconazole and
      (99m)Tc-labelled peptides/IgG at affected sites was determined scintigraphically.
      (99m)Tc-fluconazole detected C. albicans infections (T/NT ratio=3.6+/-0.47)
      without visualising bacterial infections (T/NT ratio=1.3+/-0.04) or sterile
      inflammatory processes (heat-killed C. albicans: T/NT ratio=1.3+/-0.2;
      lipopolysaccharide: T/NT ratio=1.4+/-0.1). C. albicans infections were already
      seen within the first hour after injection of (99m)Tc-fluconazole (T/NT
      ratio=3.1+/-0.2). A good correlation (R(2)=0.864; P<0.05) between T/NT ratios for
      this tracer and the number of viable C. albicans was found. Although (99m)Tc-UBI
      29-41 and (99m)Tc-hLF 1-11 were able to distinguish C. albicans infections from
      sterile inflammatory processes in mice, these (99m)Tc-labelled peptides did not
      distinguish these fungal infections from bacterial infections. It is concluded
      that (99m)Tc-fluconazole distinguishes infections with C. albicans from bacterial
      infections and sterile inflammations.

PMID- 11976809
TI  - Fluorinated amino acids for tumour imaging with positron emission tomography.
AB  - The currently preferred radiopharmaceutical for positron emission tomography
      (PET) in oncology is 2-[(18)F]fluoro-deoxyglucose (FDG). Increased accumulation
      of this deoxyglucose analogue in tumour cells is based on elevated glucose
      metabolism by tumour cells and subsequent trapping in the cells. In the search
      for new PET tracers, amino acids have been widely studied. A new amino acid
      tracer should preferably have similar high uptake in tumour cells but low non
      specific uptake in normal tissues and any pathology other than tumour. In recent
      years, several amino acids have been labelled with either gamma radiation
      emitting radionuclides or positron-emitting radionuclides, the most commonly used
      being carbon-11. However, the longer half-life of fluorine-18 matches better with
      the relatively slow process of protein synthesis and also facilitates shipping of
      the radiolabelled amino acids to hospitals without an on-site cyclotron or
      dedicated radiochemistry laboratory. The number of fluorinated amino acids under
      investigation is increasing, and one of the major points of discussion is the
      underlying mechanism of the tumour visualisation. While it has been shown that
      some amino acids can be used to measure the protein synthesis rate, others are
      used with the sole aim of measuring the rate of uptake into the cell. The
      differences between measuring amino acid transport (rate) and protein synthesis
      rate with (18)F-labelled amino acids are discussed.

PMID- 11976811
TI  - Tumour angiogenesis pathways: related clinical issues and implications for
      nuclear medicine imaging.
AB  - Tumour angiogenesis is essential for growth, invasion and metastasis.
      Retrospective studies suggest that it is an independent prognostic factor that
      merits prospective validation. Furthermore, as tumour blood vessels show many
      differences from normal vessels and are not genetically unstable, they form a key
      area for therapy development. However, as anti-angiogenic therapy is primarily
      cytostatic and not cytotoxic, novel tailor-made specific end-points for treatment
      monitoring are required. In this regard, suitable molecular parameters for
      imaging tumour angiogenesis by means of nuclear medicine are being explored. Here
      we review current knowledge on the multiple pathways controlling tumour
      angiogenesis and try to assess which are the most clinically relevant for nuclear
      medicine imaging. Parameters that may influence the imaging potential of
      radiopharmaceuticals for angiogenesis imaging such as molecular weight and
      structure, their targeted location within the tumour and their usefulness in
      terms of specificity and constancy of the targeted molecular pathway are
      discussed.

PMID- 11976810
TI  - Quantification of dopamine transporters in the mouse brain using ultra-high
      resolution single-photon emission tomography.
AB  - Functional imaging of small animals, such as mice and rats, using ultra-high
      resolution positron emission tomography (PET) and single-photon emission
      tomography (SPET), is becoming a valuable tool for studying animal models of
      human disease. While several studies have shown the utility of PET imaging in
      small animals, few have used SPET in real research applications. In this study we
      aimed to demonstrate the feasibility of using ultra-high resolution SPET in
      quantitative studies of dopamine transporters (DAT) in the mouse brain. Four
      healthy ICR male mice were injected with (mean+/-SD) 704+/-154 MBq
      [(99m)Tc]TRODAT-1, and scanned using an ultra-high resolution SPET system
      equipped with pinhole collimators (spatial resolution 0.83 mm at 3 cm radius of
      rotation). Each mouse had two studies, to provide an indication of test-retest
      reliability. Reference tissue kinetic modeling analysis of the time-activity data
      in the striatum and cerebellum was used to quantitate the availability of DAT. A
      simple equilibrium ratio of striatum to cerebellum provided another measure of
      DAT binding. The SPET imaging results were compared against ex vivo
      biodistribution data from the striatum and cerebellum. The mean distribution
      volume ratio (DVR) from the reference tissue kinetic model was 2.17+/-0.34, with
      a test-retest reliability of 2.63%+/-1.67%. The ratio technique gave similar
      results (DVR=2.03+/-0.38, test-retest reliability=6.64%+/-3.86%), and the ex vivo
      analysis gave DVR=2.32+/-0.20. Correlations between the kinetic model and the
      ratio technique ( R(2)=0.86, P<0.001) and the ex vivo data ( R(2)=0.92, P=0.04)
      were both excellent. This study demonstrated clearly that ultra-high resolution
      SPET of small animals is capable of accurate, repeatable, and quantitative
      measures of DAT binding, and should open up the possibility of further studies of
      cerebral binding sites in mice using pinhole SPET.

PMID- 11976813
TI  - Can SPET imaging of dopamine uptake sites replace PET imaging in Parkinson's
      disease? For.

PMID- 11976814
TI  - Can SPET imaging of dopamine uptake sites replace PET imaging in Parkinson's
      disease? Against.

PMID- 11976816
TI  - European system for reporting adverse reactions to and defects in
      radiopharmaceuticals: annual report 2000.

PMID- 11976815
TI  - Atypical chest pain, myocardial perfusion SPET and left main stem occlusion.

PMID- 11976817
TI  - Characterization of a new hemoglobin variant: Hb Badalona (beta31[B13]Leu-->Val).
AB  - Hemoglobin (Hb) Badalona was identified in a 35-year-old Spanish female and two
      other family members. All affected subjects presented erythrocytosis and
      increased oxygen affinity (P(50): 21 mmHg). Hemoglobinopathy was not detected
      with electrophoretic methods. It was, however, separated and quantified by cation
      exchange and reverse-phase high-performance liquid chromatography. Hb Badalona
      accounted for 35% of the total Hb. No significant clinical symptoms were found to
      be related to this hemoglobinopathy. This is the first case of a Leu-->Val
      replacement at position beta31(B13) reported in the world literature.

PMID- 11976818
TI  - Treatment of anemia in low-risk myelodysplastic syndromes with amifostine. In
      vitro testing of response.
AB  - Amifostine (AMF) promotes in vitro growth and survival of hematopoietic
      progenitors. In this study we evaluated the efficacy of AMF in the treatment of
      anemia in patients with low-risk myelodysplastic syndromes (MDS) and the possible
      predicting value for response to AMF therapy of two types of in vitro clonogenic
      assays. Two different doses of AMF, 300 mg/m2 (group A, 11 patients) or 400 mg/m2
      (group B, 16 patients), were studied. AMF was given three times weekly for 3
      weeks, i.v., followed by 2 weeks off therapy. Patients were evaluated after two
      cycles of treatment. Partially or nonresponding patients of group A received 400
      mg/m2 AMF and were reevaluated. An increase of hemoglobin (Hb) values of more
      than 2 g/dl and a 100% decrease in transfusion requirements for at least 6 weeks
      were defined as a complete response (CR) while an increase of Hb values of 1-2
      g/dl or a 50% decrease in transfusion requirements was considered as a partial
      response (PR). In group A, two out of 11 (18.1%) patients achieved a CR with the
      initial dose and one of the nine that received 400 mg/m2 AMF achieved a PR. In
      group B, three out of 16 (18.7%) patients achieved a PR; the overall response
      rate in both groups was 22.2%. In group A, bone marrow progenitor assay was
      performed pre- and post-amifostine treatment. Erythroid burst-forming units (BFU
      E) were increased in six out of 11 (54.5%) patients, and this increase preceded
      the rise in Hb levels in three of them. In group B, a clonogenic assay was
      performed in 11 out of 16 patients before AMF treatment. In vitro results after
      pretreatment with 500 microM amifostine confirmed the response of two MDS
      patients that achieved a PR. No response in vitro was observed in all eight
      nonresponding patients and in one PR patient. The lack of response in the
      clonogenic assays predicted for nonresponse to treatment with a predictive power
      of 91.8%. We conclude that 300 mg/m2 is an adequate initial treatment for low
      risk MDS patients and both clonogenic assays have a strong predicting value for
      response to treatment.

PMID- 11976819
TI  - Increased levels of soluble CD27 in the cerebrospinal fluid are not diagnostic
      for leptomeningeal involvement by lymphoid malignancies.
AB  - Soluble CD27 (sCD27) reportedly is a sensitive and specific marker for
      leptomeningeal involvement (LI) of CD27-expressing lymphoproliferations such as B
      cell non-Hodgkin's lymphoma (B-NHL) or chronic B-lymphocytic leukemia (B-CLL).
      Because morphological analysis of cerebrospinal fluid (CSF) in patients suspected
      of LI is false negative in one-third of patients, a diagnostic marker for LI by B
      NHL or B-CLL would be very valuable. sCD27 was determined in the first CSF sample
      from each of 102 unselected patients submitted for (immuno)morphologic detection
      of malignant cells. The patients were considered to have LI if either
      (immuno)morphologic analyses showed tumor cells or if neuroradiological
      evaluation showed typical abnormalities consistent with LI. Patients were
      suspected of having LI if CSF samples revealed atypical lymphocytes and/or if
      clinical symptoms and signs suggestive of LI were present, but clinical follow-up
      was shorter than 3 months because of deterioration of the patient. LI was
      considered absent if (immuno)morphologic analyses of CSF samples were negative
      without evidence for LI during 3 months of clinical follow-up. In patients with
      chronic lymphoproliferative disorders [mainly B-non-Hodgkin's lymphoma (NHL)],
      sCD27 concentrations were significantly higher in the CSF samples of 16 patients
      with confirmed or suspected LI than in those of 46 patients without LI. However,
      sCD27 was also increased in a variety of other predominantly inflammatory
      neurological disorders including herpes simplex and zoster infections. The
      positive predictive value of sCD27 determination for LI was only 54%, but the
      negative predictive value was 92%. Normal sCD27 concentrations in CSF samples of
      patients with chronic lymphoproliferation makes LI unlikely, but the
      determination of CSF sCD27 is not sufficiently specific to serve as a reliable
      tumor marker.

PMID- 11976820
TI  - In vitro megakaryocyte expansion in patients with delayed platelet engraftment
      after autologous stem cell transplantation.
AB  - Increasing the number of megakaryocytic cells in stem cell transplants by ex vivo
      expansion culture may provide an approach to accelerate platelet engraftment
      after high-dose chemotherapy. However, it is unknown if a relationship exists
      between the expansion potential of progenitor cells and the time to platelet
      engraftment in vivo. Therefore, we questioned if those patients who potentially
      would benefit most from expanded cell supplements are able to generate
      megakaryocytic cells efficiently in vitro. The in vitro megakaryocyte
      proliferation was analyzed from 19 leukapheresis samples from a group of multiple
      myeloma patients who all showed rapid neutrophil engraftment, but varied from 7
      to 115 days post-transplant to achieve platelet levels >20x10(9)/l. CD34+ cells
      were isolated and analyzed for their potential to form megakaryocytic colonies
      (CFU-Mk) in colony assays and megakaryocytic (CD61+) cells in suspension
      cultures. The frequency and size of CFU-Mk and the expansion potential of CD61+
      cells varied eightfold between individual patients. A similar range was found
      with CD34+ cells isolated from normal bone marrow (n=9). Rapid platelet
      engraftment occurred in patients receiving both high or low CFU-Mk doses and with
      high and low expansion of CD61+ cells. Four patients who experienced prolonged
      (>3 weeks) thrombocytopenia received low CFU-Mk doses, but the expansion
      potential was around median values or higher. Therefore, we conclude that the
      megakaryocyte proliferation is not impaired and that in vitro expansion could
      increase the number of megakaryocytic cells, although other factors could be more
      relevant in platelet engraftment in this group of patients.

PMID- 11976821
TI  - The value of ablating oto-rhino-laryngological (ORL) foci before haematopoietic
      stem cell transplantation (HSCT).
AB  - Between June 1996 and May 1997, 92 patients underwent haematopoietic stem cell
      transplantation (HSCT) for haematological malignancies. To participate in a
      prospective single-centre trial to evaluate oto-rhino-laryngological (ORL)
      related problems, 43 of these patients (27 male, 16 female, median age 38) signed
      an informed consent. A questionnaire about ORL related problems was assessed
      before and after HSCT. Only 21 of the patients (49%) could be fully examined
      after transplantation because of overall mortality and follow-up realised by
      other health care centres. In the deceased patients, however, a close review of
      the patients' notes was carried out. An ORL focus was not identified as the cause
      of death in any of the deceased. Pre-transplant examination revealed 15 patients
      with ORL relevant infectious foci. To make urgent HSCT possible, surgical pre
      transplant ablation of chronic ORL infection sites took place in four patients
      only. In this cohort, pre-transplant ORL pathology was not amplified after HSCT.
      None of the 11 patients presenting ORL foci before transplantation experienced
      enhancement of ORL disease. These data suggest that the indication for surgical
      intervention with regards to ORL infection prior to HSCT should be regarded
      cautiously. However, the potential risk of dissemination of a pre-existing fungal
      infection from an ORL site should be considered and treated on a case-by-case
      basis.

PMID- 11976823
TI  - Thrombotic thrombocytopenic purpura and pregnancy: a case report and a review of
      the literature.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the
      microcirculation of multiple organ systems. Plasma therapy has significantly
      reduced the mortality rate. Infections, pregnancy, cancers, drugs, and surgery
      were frequently associated with the initial episodes and relapses. Women who are
      either pregnant or in the postpartum period make up 10-25% of TTP patients,
      suggesting the interrelationship between TTP and pregnancy. The introduction of
      aggressive treatment with plasma transfusion or plasmapheresis improved maternal
      and fetal survival rates. We describe a case of a first successful pregnancy
      concomitant to a late relapse of TTP, in which the identification of important
      risk factors for both TTP and pregnancy allowed us easier hematological and
      obstetrical management. Proposed guidelines for pregnancy-related TTP management
      and a brief review of current treatment options for this rare condition are also
      included.

PMID- 11976824
TI  - Agnogenic myeloid metaplasia associated with Klinefelter syndrome: a case report.
AB  - Klinefelter syndrome is the most commonly diagnosed sex chromosome disorder among
      males. It is usually associated with 47 chromosomes, including two Xs and one Y.
      The formal cytogenetic designation for Klinefelter syndrome is 47, XXY; the extra
      sex chromosome is due to meiotic chromosomal nondisjunction. Increased risk of
      various malignant diseases has been recognized among patients with different
      congenital chromosomal abnormalities. Since the early 1960s, numerous reports
      have appeared of an increased risk of malignant neoplasms among patients with
      Klinefelter syndrome. Evidence suggests a correlation with increased incidences
      of germ cell tumors and breast cancers. Whether these patients are at an
      increased risk of hematologic malignant disease, especially acute leukemia, is
      still uncertain. This report describes a patient with agnogenic myeloid
      metaplasia and Klinefelter syndrome, an association not previously reported.

PMID- 11976822
TI  - Hereditary spherocytosis and hemochromatosis.
AB  - A 37-year-old male, splenectomized at the age of 1 year, was admitted to the ward
      with severe chest pain and signs of cardiogenic shock. Clinical investigations
      revealed the presence of both hemochromatosis and hereditary spherocytosis (HS).
      HLA typing showed A3,B7 and A24,B57 haplotypes and genetic analysis revealed
      homozygosity for the C282Y mutation. A family study was performed. The parents
      and four brothers were heterozygous for the C282Y mutation. Two of the brothers
      also presented high levels of iron stores and they had been splenectomized
      because of HS, while two other siblings had neither spherocytosis nor
      hemochromatosis. The mother had a mild anemia with dehydrated red blood cells
      (RBC), while the father appeared to have low-density, but normal RBC; none of
      them presented with spherocytosis. All siblings with spherocytosis and elevated
      iron stores showed a RBC density distribution similar to the mother. We present
      the first case with genetically proven hemochromatosis in combination with
      spherocytosis, focusing on the various possibilities of iron accumulation in
      individuals with spherocytosis and heterozygosity for the C282Y mutation.

PMID- 11976825
TI  - Lymphoid preponderance and the absence of basophilia and splenomegaly are
      frequent in m-bcr-positive chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) with a minor bcr-abl transcript is a rare
      entity. We describe a 66-year-old female who was diagnosed with CML in the
      chronic phase. Molecular analysis of her Philadelphia chromosome using the
      reverse transcriptase polymerase chain reaction and subsequent sequencing
      revealed a minor bcr-abl transcript. Monocytosis resembling chronic
      myelomonocytic leukemia was observed without splenomegaly and basophilia. Her
      clinical course was indolent and maintained the chronic phase of CML for nearly 3
      years under hydroxyurea treatment. A review of the 23 cases of m-bcr CML
      including this case showed the presence of monocytosis and the absence of
      basophilia and splenomegaly in 55.0%, 55.0%, and 70.0% of patients, respectively.
      The absence of basophilia was a significant finding in patients without
      monocytosis ( P=0.01). Although the hematological features or clinical outcomes
      were variable in m-bcr CML cases, all three cases at the onset of the blastic
      phase showed lymphoid crisis, implying an increased lymphoid leukemogenicity of
      minor bcr-abl transcripts.

PMID- 11976827
TI  - Primary follicular lymphoma arising in the ampulla of Vater.
AB  - Primary gastrointestinal lymphomas constitute more than one-third of all
      extranodal lymphomas, but among them follicular lymphomas (FL) are infrequent,
      accounting for only 1-4%. We report the case of a 55-year-old man diagnosed with
      a FL of the ampulla of Vater. He complained of dyspepsia. An upper
      gastroendoscopic study 1 year before showed a slight enlargement of the papilla
      with the biopsy initially interpreted as atypical follicular hyperplasia. The
      study performed because of persistence of the symptoms again showed an enlarged
      papilla, and the histological examination was diagnostic of FL (CD10+, bcl-2+).
      The full staging study did not show other FL involvement. The patient was treated
      with six courses of cyclophosphamide, hydroxydaunomycin, vincristine, and
      prednisone (CHOP), and the endoscopy as well as the biopsies revealed no
      abnormalities since the third course of chemotherapy. After 2 years of follow-up
      he remains asymptomatic and the gastroendoscopic study is normal.

PMID- 11976826
TI  - Lymphomatous polyp of mantle cell type in the duodenum complicated by gastric
      cancer: a case of trisomy 3 and t(11;14)(q13;q32).
AB  - We experienced a rare case of a lymphomatous polyp of mantle cell type forming a
      polypoid mass lesion in the duodenum bulbous together with advanced gastric
      cancer. A total gastrectomy was performed, and the specimen revealed atypical
      small- to medium-sized lymphoid cells with indented nuclei, which infiltrated the
      Peyer's patch and formed a nodular mass in the lamina propria and submucosa of
      the duodenum. The lymphoma cells also infiltrated the lymphoid follicle of the
      gastric mucosa, spleen, and regional lymph node with a typical mantle zone
      pattern. Flow cytometric analysis of the single cells of the lymph node and
      immunohistochemistry of a paraffin-embedded specimen revealed that the lymphoma
      cells expressed surface CD5, CD19, CD20, and nuclear cyclin D1. Chromosomal
      analysis of this single cell suspension revealed that these lymphoma cells have
      trisomy 3 in conjunction with t(11;14)(q13;q32), which is frequently seen in
      mucosa-associated lymphoid tissue lymphomas (MALToma) in the stomach and is also
      reported in mantle cell lymphoma as a secondary genetic alteration. Our report
      suggests that trisomy 3 may be a common chromosomal abnormality in lymphomatous
      polyps of mantle cell type.

PMID- 11976828
TI  - Topotecan-induced topoisomerase IIalpha expression increases the sensitivity of
      the CML cell line K562 to subsequent etoposide plus mitoxantrone treatment.
AB  - PURPOSE: A new chemotherapy regimen was designed for leukemia to improve response
      to therapy and elucidate the possible underlying mechanisms responsible for its
      efficacy. METHODS: Cells of the chronic myelogenous leukemia (CML) cell line,
      K562, were treated singly, in combination, and in sequence with clinically
      equivalent dosages of topotecan, which targets topoisomerase I (Topo I), and
      etoposide and mitoxantrone, which target topoisomerase II (Topo II), to determine
      the best treatment. Apoptosis, early cell deaths, and cell cytotoxicities in drug
      treated cells were determined with annexin V and propidium iodide staining and
      MTT assays, respectively. Confocal microscopy and RT-PCR showed the cellular
      locations and relative increases in Topo IIalpha in topotecan-treated cells. The
      double comet assay of individual cells showed simultaneously free Topo proteins,
      non-Topo-associated DNA, and Topo-DNA complexes in drug-induced DNA fragments.
      RESULTS: Sequential treatment with topotecan on days 1-3, followed by
      etoposide+mitoxantrone on days 4, 5, 9 and 10 resulted in 100% cell death whereas
      treatments involving administration of drugs singly or simultaneously resulted in
      less cell kill. The cytotoxicity results in cells treated for fewer days with the
      same sequential chemotherapy regimen showed the same trend, and adequate
      surviving cells for the experiments on the cellular and molecular mechanisms of
      drug action were produced. An increase in Topo IIalpha mRNA from RT-PCR 1 h after
      topotecan treatment was observed. Observations on K562 cells treated sequentially
      with topotecan followed by etoposide, mitoxantrone or etoposide+mitoxantrone were
      as follows: (1) Topo IIalpha protein levels increased and relocated from the
      cytoplasm into the nucleus as detected by confocal microscopy, (2) Topo IIalpha
      DNA complexes increased and were associated with fragmented DNA (positive double
      comets) as detected by protein-DNA double comet assay, and (3) Topo I and Topo
      IIbeta proteins were not associated with fragmented DNA. Topotecan-induced Topo
      IIalpha protein levels correlated with increased numbers of positive double
      comets and reduction of cell viability. CONCLUSIONS: Our results showed that Topo
      IIalpha protein induction after Topo I-directed drug treatment enhanced the
      sensitivity of cells to subsequent exposure to Topo II-directed drugs. Timed
      sequential chemotherapy with topotecan followed by etoposide+mitoxantrone is an
      effective regimen to ablate CML cancer cells.

PMID- 11976829
TI  - Change in pharmacokinetic and pharmacodynamic behavior of gemcitabine in human
      tumor xenografts upon entrapment in vesicular phospholipid gels.
AB  - PURPOSE: The in vivo pharmacokinetics (PK), biodistribution and antitumor
      activity of a new liposomal formulation of gemcitabine (GemLip) were compared to
      the conventional (clinical) formulation of gemcitabine (GemConv). METHODS:
      Gemcitabine was entrapped in a vesicular phospholipid gel (VPG) consisting of
      densely packed liposomes. Redispersed VPG containing GemLip consisted of 33%
      liposomally entrapped and 67% free gemcitabine. The in vivo efficacies of GemLip
      and GemConv were compared using the subcutaneously growing human soft tissue
      sarcoma SXF 1301 and the orthotopically growing human bladder cancer BXF 1299T.
      PK and biodistribution were evaluated using radiolabeled drug and lipid in SXF
      1301 tumor-bearing nude mice. RESULTS: GemLip was highly active in SXF 1301 at a
      gemcitabine dose of 6-9 mg/kg (days 1, 8 and 15; dose near the MTD). In the 6
      mg/kg groups, complete tumor remissions were observed in seven of eight mice.
      Equimolar doses of GemConv resulted in only moderate tumor growth inhibition.
      Even at equitoxic doses (360 mg/kg given on days 1, 8 and 15, or 120 mg/kg on
      days 1, 5 and 8) GemConv was less active than GemLip. Furthermore, GemLip was
      active in the orthotopically growing BXF 1299T bladder cancer model at 6 mg/kg
      and prevented distant organ metastasis. In the PK study, GemLip achieved a 35
      fold higher plasma AUC (1680 mg x h/ml) than GemConv (47.6 mg x h/ml). The serum
      half-lives were 0.15 h for free gemcitabine and 13.3 h for liposomal gemcitabine
      (6 mg/kg each i.v.). Moreover, gemcitabine levels in tumors were fourfold higher
      following injection of GemLip than following injection of GemConv. CONCLUSIONS:
      GemLip is a highly effective gemcitabine delivery system which results in
      superior gemcitabine pharmacodynamics and PK than GemConv. The enhanced in vivo
      efficacy might be explained by sustained release and passive tumor targeting.

PMID- 11976830
TI  - Pharmacokinetics of oxaliplatin (NSC 266046) alone and in combination with
      paclitaxel in cancer patients.
AB  - Oxaliplatin (OPT), a third-generation platinating agent, is currently being
      evaluated in a phase II clinical trial in head and neck cancer patients and in a
      phase I clinical trial in combination with paclitaxel (TXL). PURPOSE: The aim of
      this study was to investigate the pharmacokinetics and biological correlates of
      OPT alone as well as the potential pharmacokinetic interaction between OPT and
      TXL. METHODS: In the phase II study, OPT was given alone as a 2-h i.v. infusion
      at 60 mg/m(2) weekly for 4 weeks with the cycle repeated after a 2-week rest. In
      the concurrent phase I combination trial OPT was also given as a 2-h i.v.
      infusion, but followed by a 1-h i.v. infusion of TXL, weekly for 4 weeks with the
      cycle repeated after a 2-week rest. The clinical pharmacokinetics of OPT alone
      and in combination with TXL were investigated in the first cycle of each
      treatment protocol. The platinum levels in plasma, plasma ultrafiltrate (PUF) and
      urine were measured by a fully validated inductively coupled plasma mass
      spectrometry (ICPMS) method. RESULTS: In the ten patients receiving OPT alone,
      the concentration-time profiles of total platinum exhibited a biexponential
      decline both in plasma and in PUF. The peak levels of platinum were 2.72+/-0.41
      microg/ml in plasma and 1.36+/-0.42 microg/ml in PUF at the end of the OPT
      infusion, and the platinum levels were still detectable at >10 ng/ml 94 h after
      the OPT infusion. The mean terminal t(1/2) values of total platinum in plasma and
      in PUF were 58.9 h and 22.8 h, respectively. The AUC of ultrafilterable platinum
      represented about 10% of that of the total plasma platinum. The platinum levels
      in the DNA fraction of peripheral white blood cells (WBC) correlated with the
      platinum levels in PUF ( r=0.77, P<0.01). In the phase I combination study, the
      dose level of OPT was escalated from 35 mg/m(2) to 60 mg/m(2). The concentration
      time profiles of platinum in the combination trial also showed biexponential
      decay in plasma and in PUF as exhibited by OPT alone. However, the terminal
      elimination rate constant (beta) of total plasma platinum increased at all dose
      levels of OPT when combined with TXL at 45 mg/m(2) ( P<0.05). A concomitant
      increase in clearance (CL) of total plasma platinum was observed at the OPT dose
      level of 45 mg/m(2) in combination with TXL at 45 mg/m(2). No statistically
      significant difference in the 24-h urinary elimination of total platinum was
      detected between the combination groups and the single-agent group. The AUC
      values of total platinum in PUF were proportional to OPT doses ranging from 35 to
      60 mg/m(2), whether OPT was given alone or in combination with TXL. CONCLUSIONS:
      OPT clearance may be enhanced by TXL when the two agents are used in combination
      in patients. The Pt-DNA adduct level in peripheral WBC was found to be a good
      indicator for oxaliplatin exposure in patients, and should be further exploited
      for potential tumor drug exposure.

PMID- 11976831
TI  - The pharmacokinetics of the bispecific antibody MDX-H210 when combined with
      interferon gamma-1b in a multiple-dose phase I study in patients with advanced
      cancer.
AB  - INTRODUCTION: MDX-H210 is a Fab'xFab' bispecific antibody (BsAb) constructed
      chemically by crosslinking Fab' mAb 520C9 (anti-HER-2/neu) and humanized Fab'
      mAbH22 (anti-CD64). STUDY DESIGN AND OBJECTIVES: This was a phase I dose
      escalation study of intravenous MDX-H210 (1-70 mg/m(2)) combined with
      subcutaneous IFN-gamma, 50 microg/m(2) given 24 h before the BsAb, both drugs
      being given three times a week for 3 weeks. The major objectives of the study
      were to define the safety, tolerability and pharmacokinetics of MDX-H210 when
      given with IFN-gamma on this schedule. RESULTS: The study group comprised 23
      patients (19 female, 4 male; median age 51.5 years, range 25-72 years) with
      advanced HER-2/neu-positive cancers (19 breast, 3 prostate and 1 lung).
      Inspection of the log plasma MDX-H210 concentrations-time data for both days 1
      and 17 of treatment revealed monoexponential decay in the majority of patients
      with adequate concentration-time data points. The MDX-H210 T(1/2) ranged from 2.9
      to 21.9 h. The MDX-H210 C(max) on day 1 (means+/-SD) increased from 0.30+/-0.22
      microg/ml at the 1-mg/m(2) dose tier to 86.91+/-6.46 microg/ml at 70 mg/m(2).
      Equivalent day-17 values were 0.27+/-0.30 microg/ml increasing to 147.85+/-40.23
      microg/ml. The MDX-H210 T(max) occurred at or after the end of the infusion for
      all treatments. The mean MDX-H210 total body clearance (Cl) was in the range 0.01
      0.34 ml/min per kg and the mean MDX-H210 apparent volume of distribution at
      steady-state (Vd(ss)) in the range 20-170 ml/kg, compatible with distribution
      primarily limited to the intravascular space. MDX-H210 T(1/2) increased with dose
      (ANOVA P=0.001) and Cl decreased with dose (ANOVA P=0.006). There were no
      significant changes in MDX-H210 C(max), AUC, Cl or Vd(ss) between day 1 and day
      17. CONCLUSIONS: MDX-H210 pharmacokinetics appeared saturable over the dose range
      1-70 mg/m(2), and there was no significant change in MDXH210 pharmacokinetics
      over the course of the study, or evidence of excessive accumulation of MDX-H210
      on this multiple dosing schedule. When MDX-H210 was combined with IFN-gamma, the
      estimated MDX-H210 pharmacokinetic parameters were similar to the published data
      for single-agent MDX-H210.

PMID- 11976832
TI  - Mechanism of vinorelbine-induced radiosensitization of human small cell lung
      cancer cells.
AB  - Vinorelbine (Navelbine, KW-2307), a semisynthetic vinca alkaloid, is a potent
      inhibitor of mitotic microtubule polymerization. The aims of this study were to
      demonstrate vinorelbine-induced radiosensitization of human small cell lung
      cancer (SCLC) SBC-3 cells and to elucidate the mechanisms of radiosensitization.
      A clonogenic assay demonstrated that SBC-3 cells were sensitized to radiation by
      vinorelbine using different schedules combining exposure to both. The sensitizer
      enhancement ratios (SERs) at a cell survival level of 10% were 1.42+/-0.21 to
      1.33+/-0.06, and 1.22+/-0.07 depending on schedule. Vinorelbine-induced
      radiosensitization did not depend on the schedule of the combined exposure. Flow
      cytometric analyses showed that the cells did not accumulate in the
      radiosensitive G(2)/M phase of the cell cycle after concurrent treatment with
      vinorelbine and radiation. The results of an alkaline filter elution assay
      demonstrated that in the presence of vinorelbine at 1 n M radiation-induced DNA
      strand breaks were not completely repaired at 24 h postradiation. We conclude
      that human SCLC SBC-3 cells are sensitized to radiation by vinorelbine and that a
      possible mechanisms of vinorelbine-induced radiosensitization may at least in
      part be associated with impairment of DNA repair following radiation-induced DNA
      damage.

PMID- 11976833
TI  - Induction of multidrug resistance in MOLT-4 cells by anticancer agents is closely
      related to increased expression of functional P-glycoprotein and MDR1 mRNA.
AB  - PURPOSE: The aim of this study was to investigate the multidrug resistance (MDR)
      pattern, MDR gene and P-glycoprotein (P-gp) expression, and P-gp function in drug
      induced human T-lymphoblastoid leukemia MOLT-4 sublines. METHODS: The MDR
      sublines were developed by exposing the parental MOLT-4 cells to stepwise
      increasing concentrations of anticancer drugs daunorubicin (DNR), vinblastine
      (VBL) and doxorubicin (DOX). Degrees of resistance were assessed in terms of
      IC(50) values in an MTT assay and the P-gp function was evaluated in terms of
      rhodamine 123 (Rh123) accumulation and efflux. The percentage of cells undergoing
      apoptosis was determined by flow cytometry after staining with annexin V-FITC and
      propidium iodide. The levels of P-gp and MDR mRNA expression were estimated using
      the PE-conjugated anti-P-gp monoclonal antibody 17F9 and quantitative real-time
      reverse transcription-polymerase chain reaction. RESULTS: Three MOLT-4 sublines
      were established and revealed a 2- to 115-fold resistance to the anticancer
      reagents DNR, VBL and DOX as compared to the parental cell line. The highest MDR
      was expressed in MOLT-4/DNR cells, which was overcome by the P-gp modulator,
      cyclosporin A (CsA). The resistant sublines showed a decreased accumulation and
      an increased efflux of Rh123 in proportion to the degree of resistance, and these
      were completely reversed in the presence of 8 microM CsA. The decreased apoptotic
      response in these cell lines was clearly associated with the degree of drug
      resistance. P-gp antigen and MDR1 mRNA were highly expressed in both the MOLT
      4/DNR and MOLT-4/DOX sublines. Less-resistant MOLT-4/VBL cells expressed lower
      levels of MDR1 mRNA and P-gp, even though the cell line was established by
      exposing the parental MOLT-4 cells to VBL for longer (5 months) than to the other
      two reagents (3 months). CONCLUSIONS: MOLT-4 cells were able to acquire a high
      level of drug resistance by culturing the cells in the presence of certain
      anticancer drugs, and acquisition of the resistance was relatively reagent
      specific. The degrees of resistance to the anticancer drugs were well correlated
      with the expressions of MDR1 mRNA and functional P-gp, and were also associated
      with a decreased response to apoptosis.

PMID- 11976834
TI  - Estimation of the effect of food on the disposition of oral 5-fluorouracil in
      combination with eniluracil.
AB  - AIMS: To determine the effect of food on the pharmacokinetics of 5-fluoruracil (5
      FU) taken orally with eniluracil and to compare the performance of different
      pharmacokinetic analysis methods in the detection a potential food-drug
      interaction. METHODS: In a randomized, open-label, two-way crossover study, 12
      patients received eniluracil (50 mg, orally) on days 1 and 2 and 5-FU (20
      mg/m(2), orally) on day 2 following either a 2-h fast or 20 min after a standard
      meal. Treatments were separated by 7 days. Timed blood samples were collected
      during the first two treatment periods and 5-FU concentrations determined by
      GC/MS. Data were analyzed and pharmacokinetic parameter estimates were obtained
      using a noncompartmental, two-stage and population analysis methods. RESULTS: In
      fasted individuals, the clearance/bioavailability of 5-FU was estimated to be 5.6
      l/h. The mean absorption lag-time was 0.24 h and was followed by rapid absorption
      of 5-FU. Administration of 5-FU and eniluracil with food resulted in a decrease
      in the 5-FU absorption rate constant by 90%. As a result, the peak plasma
      concentration (C(max)) of 5-FU was decreased by 21% and the time to C(max) was
      increased 2.9-fold. Clearance of 5-FU, relative bioavailability, and area under
      the plasma concentration vs time curve (AUC) remained unchanged with
      coadministration of food. Similar results were obtained using all three data
      analysis methods. CONCLUSIONS: Administration of food with oral 5-FU and
      eniluracil slowed absorption of 5-FU and decreased 5-FU C(max), but did not
      effect AUC. Further investigation of the incorporation of population
      pharmacokinetic approaches in food effect studies is warranted.

PMID- 11976835
TI  - Accelerated recovery from irradiation injury by angiotensin peptides.
AB  - PURPOSE: Angiotensin peptides have been shown to affect the proliferation and
      chemotaxis of multiple cell types. More recent studies in this laboratory have
      shown that angiotensin II (AII) can increase colony formation and proliferation
      by hematopoietic progenitors and mesenchymal cells in vitro. As white blood cell
      (WBC) recovery after bone marrow injury requires progenitor proliferation, the
      effect of AII and angiotensin (1-7) [A(1-7)], a non-hypertensive fragment of AII,
      on recovery from total body irradiation was evaluated in C57Bl/6 mice. MATERIALS
      AND METHODS: The effect of angiotensin peptides on hematopoietic recovery and the
      number of progenitors in the bone marrow of irradiated C57Bl/6 mice was
      evaluated. RESULTS: Treatment of animals with angiotensin peptides accelerated
      hematopoietic recovery and increased the number of hematopoietic progenitors in
      bone marrow and in the blood. The increase in WBC concentration continued for a
      longer time after cessation of AII therapy than after treatment with filgrastim.
      Specifically, the number of WBCs continued to increase 21 days after irradiation
      with 7 days of angiotensin peptide administration. In contrast, the number of
      WBCs increased through day 13 with 7 days of filgrastim administration. On day 35
      after irradiation (28 days after the last treatment), AII was shown to have
      increased the number of CFU-GM in the bone marrow of irradiated mice, whereas
      filgrastim administration had not. Angiotensin peptides also reduced the drop in
      platelet concentration after irradiation and increased the number of
      megakaryocyte precursors and megakaryocytes in the bone marrow. Receptor blocking
      studies indicated that losartan, an antagonist of the angiotensin type 1
      receptor, blocked recovery of WBC levels in response to treatment with AII. In
      contrast, the increase in WBC levels in response to treatment with A(1-7), a
      ligand for other angiotensin receptors, was not affected by losartan.
      CONCLUSIONS: These findings suggest that these peptides utilize distinct
      receptors in the stimulation of hematopoietic recovery. In summary, systemic
      administration of angiotensin peptides led to an acceleration in hematopoietic
      recovery after irradiation. These peptides act to stimulate the formation of bone
      marrow progenitors, thereby facilitating recovery after myelosuppressive
      irradiation.

PMID- 11976836
TI  - Enhanced antitumor activity of irofulven in combination with thiotepa or
      mitomycin C.
AB  - PURPOSE: Irofulven (6-hydroxymethylacylfulvene, MGI 114, NSC 683863) is a
      semisynthetic derivative of illudin S, a toxin present in the Omphalotus
      mushroom. Irofulven has demonstrated activity against a broad range of solid
      tumors in both xenograft models and human trials. The potential application of
      administering irofulven in combination with aziridine-containing chemotherapeutic
      agents was evaluated in this study. METHODS: Human lung carcinoma MV522 cells and
      BALB/c athymic mice bearing the human lung carcinoma MV522 xenograft were used to
      evaluate the activity of irofulven in combination with aziridine-containing
      drugs. RESULTS: Irofulven in combination with either thiotepa or mitomycin C
      demonstrated a strong synergistic (supraadditive) activity both in vitro and in
      vivo, that exceeded results obtained with monotherapy at the same or higher doses
      of these agents. The majority of xenograft-bearing animals that received subtoxic
      doses of irofulven, and either thiotepa or mitomycin C, demonstrated a complete
      cure. In contrast, there was no detectable synergistic activity between irofulven
      and other aziridine-containing drugs, including AZQ and thiotepa metabolites such
      as TEPA or AZD. CONCLUSIONS: These results indicate that the therapeutic activity
      of irofulven is enhanced when combined with mitomycin C or thiotepa, and further
      evaluation of these combinations is therefore warranted.

PMID- 11976837
TI  - Radiolabeled 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU) and 2'-fluoro-5
      methyldeoxyuracil-beta -D-arabinofuranoside (FMAU) as tumor-imaging agents in
      mice.
AB  - PURPOSE: The purpose of the present study was to evaluate, in conjunction with
      the National Cancer Institute, the feasibility of using two thymidine analogs, 2'
      fluorodeoxyuracil-beta-D-arabinofuranoside (FAU, NSC-678515) and 2'-fluoro-5
      methyldeoxyuracil-beta-D-arabinofuranoside (FMAU, NSC-678516), as 18-fluorine
      labeled positron emission tomography (PET) imaging agents. METHODS: The in vivo
      distribution and DNA incorporation of [2-(14)C]FAU, [2-(14)C]FMAU, and [2
      (14)C]thymidine (as a control) were studied in SCID mice bearing human xenografts
      of T-cell leukemia CCRF-CEM. Levels of drug-associated radioactivity in blood,
      tumor and normal tissues including liver, kidneys, heart, lungs, spleen, brain,
      and skeletal muscle were determined. RESULTS: At 1 h after dosing, radioactivity
      from all three compounds was distributed in a generally nonspecific manner,
      except that spleen and tumor tissue had relatively high concentrations of
      radioactivity from [(14)C]thymidine. At 4 h after dosing, the concentrations of
      radioactivity from [(14)C]thymidine and [(14)C]FMAU were relatively high in
      spleen and tumor tissue, and that from [(14)C]FAU was highest in tumor tissue.
      The tumor/skeletal muscle concentration ratios were 2.25+/-0.69 and 3.07+/-0.42
      for [(14)C]FAU and [(14)C]FMAU, respectively. At 24 h after dosing, only spleen
      and tumor tissues contained appreciable amounts of radioactivity from either
      compound. In tumor tissue, the levels of radioactivity from [(14)C]FMAU were two-
      to threefold greater than those from [(14)C]thymidine or [(14)C]FAU. Examination
      of purified genomic DNA from tumor, liver, kidneys, brain, and skeletal muscle
      showed that, at 24 h after dosing, only DNA from tumor tissue contained
      appreciable concentrations of radioactivity. Radioactivity from [(14)C]FMAU in
      tumor DNA was 45% greater than that from [(14)C]thymidine and about threefold
      greater than that from [(14)C]FAU. CONCLUSIONS: The extent of accumulation of
      [(14)C]FMAU in tumor tissue and incorporation into tumor DNA indicate that
      [(18)F]FMAU could be useful as a functional PET tumor-imaging agent.

PMID- 11976838
TI  - Phase II and pharmacokinetic study of GL331 in previously treated Chinese gastric
      cancer patients.
AB  - PURPOSE: A phase II and pharmacokinetic study was designed to assess the efficacy
      and toxicity profile of an epidophyllotoxin analogue, GL331, in previously
      treated Chinese gastric cancer patients, with concurrent pharmacokinetic
      evaluation of the drug's metabolism. MATERIAL AND METHODS: GL331 was given at 200
      mg/m(2) as a daily 3-h infusion for 5 days every 4 weeks. RESULTS: Enrolled in
      the study were 15 patients. One patient died from neutropenic sepsis before
      evaluation, one patient did not receive the full dose for reasons unrelated to
      GL331, nine patients had progressive disease with a median survival of 80 days,
      and five had stable disease with a median survival of 240 days. Grade 3 and 4
      myelosuppression occurred in 10 of the 15 patients, with one death from
      neutropenic sepsis. This patient's peak GL331 concentration was 16.8 microg/ml,
      which was high compared to the mean peak drug concentration of 6+/-4.1 microg/ml.
      The mean systemic GL331 clearance was 12.1+/-7.2 l/h per m(2), much lower than
      23.3+/-8.2 l/h per m(2) found in the phase I trial. Topoisomerase IIalpha was
      determined by immunohistochemistry and overexpression was detected in 3 of 11
      specimens. CONCLUSIONS: GL331 was ineffective at this dose and schedule in this
      group of patients in spite of adequate blood levels of the drug.

PMID- 11976839
TI  - Iron-oxide-enhanced MR lymphography: just a new toy or a breakthrough?

PMID- 11976840
TI  - Traumatic injuries: organization and ergonomics of imaging in the emergency
      environment.
AB  - Management of trauma patients relies on a simple but obvious concept: Time is
      life! This is a challenge to the emergency radiologist in his evaluation of the
      radiological admission survey of severe trauma patients, since the latter need a
      quick and thorough survey of craniocerebral, cervical, thoracic, abdominal, and
      limb lesions. This article reviews the architectural design and the management
      strategies required to fulfill this purpose. Whereas plain films and
      ultrasonography have precise but limited indications, multislice spiral CT (MSCT)
      shows an increasingly preponderant role in the imaging evaluation of trauma
      patients, as demonstrated through three examples (aortic, spine, and
      craniocerebral trauma). Multislice CT affords a comprehensive assessment of
      trauma patients' injuries and allows for their categorization according to the
      severity of traumatic lesions. With respect to the MSCT data volume, the
      emergency radiologists have to modify the strategies in their examination reading
      and result transmission, with a growing role attributed to two- and three
      dimensional reconstructions. The emergency radiologist's role is thus of prime
      importance in the management of trauma patients, and this all the more so since
      development of interventional radiology affords therapeutic procedures
      alternative to surgery. Trauma radiology and emergency radiology on the whole
      will assert themselves as consistent and thorough areas of subspecialization.

PMID- 11976841
TI  - Traumatic injuries: role of imaging in the management of the polytrauma victim
      (conservative expectation).
AB  - Abdominal US and CT play an important role in the initial management of blunt
      trauma in adults. Ultrasound is an excellent method for detection of free intra
      abdominal fluid. It is the modality of choice for initial screening and enables
      selection of hemodynamically unstable trauma victims with severe hemoperitoneum
      for immediate surgery. However, even in experienced hands, US is not sufficient
      to rule out organ injuries reliably. Computed tomography, and particularly
      multislice CT (MSCT), has several major advantages over US and is currently
      unsurpassed for the detection of blunt visceral injuries in the abdomen. Computed
      tomography has a high sensitivity for the detection of parenchymal splenic and
      hepatic injuries. Injuries of the gastrointestinal tract may be detected with
      good sensitivity provided that adequate examination technique and careful
      diagnostic interpretation are combined. The value of CT-based injury-grading
      systems for predicting the outcome of conservative treatment remains unproven;
      however, demonstration of direct vascular injuries with CT, e.g., the
      intrasplenic "contrast blush" sign, may indicate a high likelihood that
      conservative treatment will fail, thus warranting angiographic embolization or
      surgery. Monitoring of conservatively treated trauma victims by means of repeat
      CT studies enables early detection of a variety of delayed, clinically silent
      complications of trauma, e.g., posttraumatic biloma or bowel devascularization.
      Catheter angiography may be reserved to selected cases with vascular injuries
      proven on CT.

PMID- 11976842
TI  - Traumatic injuries: radiological hemostatic intervention at admission.
AB  - Blunt trauma victims and selected patients with penetrating trauma are
      systematically investigated after resuscitation and hemodynamic stabilization
      with cross-sectional imaging. Computed tomography is a good predictor of the need
      for hemostatic arteriographic embolization, based on contrast medium
      extravasation observed on CT. In centers admitting polytrauma patients, the CT
      and angiography units should be installed together within the emergency
      environment. Trauma-dedicated interventional radiologists should be on call for
      optimal patient management. Posttraumatic retroperitoneal and pelvic bleeding is
      a primary indication for angiographic hemostasis, together with orthopedic
      fixation of pelvic bone fractures. Angiography should be carried out rapidly,
      before the patient decompensates for considerable blood loss. In patients with
      visceral bleeding, arterial embolization can obviate primary surgery or
      potentializes surgical intervention and contributes to changing hierarchy of
      injuries to be treated surgically. Failure to achieve primary hemostasis may
      occur according to the type of specific organ injury and coagulation and
      metabolic parameters of the patient. Postembolization complications are few and
      are usually non-life-threatening and rarely carry definitive sequelae.

PMID- 11976843
TI  - Traumatic injuries: imaging and intervention in post-traumatic complications
      (delayed intervention).
AB  - The nonoperative management (NOM) of abdominal trauma has gained increasing
      acceptance over the past decade. This approach has been extended to severe trauma
      patients previously considered as candidates for surgery. Consequently, the
      incidence of delayed and uncommonly encountered complications has increased.
      Causes of delayed complications are multiple and include: (a) abnormal or
      insufficient injury healing process; (b) retention of necrotic tissue; (c)
      secondary infection of initially sterile collections; and (d) underestimation of
      injury severity. The purpose of this review article is to explain the role of
      various imaging modalities in detecting post-traumatic delayed complications and
      to highlight the usefulness of minimally invasive techniques, including
      laparoscopy, biliary endoscopy, therapeutic angiography and image-guided
      drainage. Subsequent complications, which do not necessarily negatively influence
      the final outcome, are often predictable, virtually obligatory consequences of
      the successful NOM of high-grade or complex abdominal injuries. Between 50 and
      60% of those patients with grade-IV or grade-V liver or splenic lacerations
      require some type of interventional treatment; therefore, indiscriminate
      discharge of patients with solid organ injury managed conservatively may be
      potentially harmful. As the incidence of complications is higher for more severe
      grade-IV or grade-V liver, spleen, or kidney injuries, scheduled follow-up CT
      scans may be rational in this subset of patients to identify potential
      complications amenable to early application of interventional techniques. Follow
      up CT scans are unnecessary in stable adults or children with low-grade injury.
      Delayed splenic or hepatic rupture is one of the major concerns because this type
      of complication remains difficult to predict and historically often requires
      emergent surgery. These ruptures may benefit from NOM, should the same criteria
      as for primary rupture be respected. Conversely, parenchymatous focal pooling of
      contrast on initial CT is a good predictor for the development of delayed
      vascular malformation. In children, as a large part of splenic and hepatic
      vascular malformations resolve spontaneously, expectant observation may be
      indicated provided that a strict imaging follow-up is performed until complete
      disappearance of these lesions. If needed, embolization of parenchymal vascular
      lesions should be performed as selectively as possible in order to avoid
      functional parenchyma loss and to reduce the risk of secondary infection of
      hematoma or ischemic tissue. Technical improvements, such as microcatheter
      systems and direct percutaneous approach to targeted lesions, have widened the
      potential for safe endovascular management of acquired vascular malformations.
      Advantages and disadvantages relative to the different embolic agents are
      explained. Endoscopic retrograde pancreatography is the chief investigational
      tool for detecting biliary and pancreatic ducts injuries. The respective roles of
      endoscopic, percutaneous and surgical approaches in the management of these
      complications are discussed. The CT scan and ultrasound-guided drainage provide
      effective nonoperative options in the management of post-traumatic parenchymatous
      and (retro)-peritoneal collections. Treatment modalities of less common
      complications, such as bowel stricture or perforation, mesenteric vascular
      injuries and renal trauma-induced hypertension, are reviewed.

PMID- 11976844
TI  - New frontiers in CT imaging of airway disease.
AB  - Combining helical volumetric CT acquisition and thin-slice thickness during
      breath hold provides an accurate assessment of both focal and diffuse airway
      diseases. With multiple detector rows, compared with single-slice helical CT,
      multislice CT can cover a greater volume, during a simple breath hold, and with
      better longitudinal and in-plane spatial resolution and improved temporal
      resolution. The result in data set allows the generation of superior multiplanar
      and 3D images of the airways, including those obtained from techniques developed
      specifically for airway imaging, such as virtual bronchography and virtual
      bronchoscopy. Complementary CT evaluation at suspended or continuous full
      expiration is mandatory to detect air trapping that is a key finding for
      depicting an obstruction on the small airways. Indications for CT evaluation of
      the airways include: (a) detection of endobronchial lesions in patients with an
      unexplained hemoptysis; (b) evaluation of extent of tracheobronchial stenosis for
      planning treatment and follow-up; (c) detection of congenital airway anomalies
      revealed by hemoptysis or recurrent infection; (d) detection of postinfectious or
      postoperative airway fistula or dehiscence; and (e) diagnosis and assessment of
      extent of bronchiectasis and small airway disease. Improvement in image analysis
      technique and the use of spirometrically control of lung volume acquisition have
      made possible accurate and reproducible quantitative assessment of airway wall
      and lumen areas and lung density. This contributes to better insights in
      physiopathology of obstructive lung disease, particularly in chronic obstructive
      pulmonary disease and asthma.

PMID- 11976845
TI  - Visual classification of emphysema heterogeneity compared with objective
      measurements: HRCT vs spiral CT in candidates for lung volume reduction surgery.
AB  - The aim of this study was to investigate whether spiral CT is superior to high
      resolution computed tomography (HRCT) in evaluating the radiological morphology
      of emphysema, and whether the combination of both CT techniques improves the
      evaluation in patients undergoing lung volume reduction surgery (LVRS). The
      material consisted of HRCT (with 2-mm slice thickness) and spiral CT (with 10-mm
      slice thickness) of 94 candidates for LVRS. Selected image pairs from these
      examinations were evaluated. Each image pair consisted of one image from the
      cranial part of the lung and one image from the caudal part. The degree of
      emphysema in the two images was calculated by computer. The difference between
      the images determined the degree of heterogeneity. Five classes of heterogeneity
      were defined. The study was performed by visual classification of 95 image pairs
      (spiral CT) and 95 image pairs (HRCT) into one of five different classes of
      emphysema heterogeneity. This visual classification was compared with the
      computer-based classification. Spiral CT was superior to HRCT with 47% correct
      classifications of emphysema heterogeneity compared with 40% for HRCT-based
      classification ( p<0.05). The combination of the techniques did not improve the
      evaluation (42%). Spiral CT is superior to HRCT in determining heterogeneity of
      emphysema visually, and should be included in the pre-operative CT evaluation of
      LVRS candidates.

PMID- 11976846
TI  - Automatic detection of pulmonary nodules at spiral CT: clinical application of a
      computer-aided diagnosis system.
AB  - The aim of this study was to evaluate a computer-aided diagnosis (CAD)
      workstation with automatic detection of pulmonary nodules at low-dose spiral CT
      in a clinical setting for early detection of lung cancer. Eighty-eight
      consecutive spiral-CT examinations were reported by two radiologists in
      consensus. All examinations were reviewed using a CAD workstation with a self
      developed algorithm for automatic detection of pulmonary nodules. The algorithm
      is designed to detect nodules with diameters of at least 5 mm. A total of 153
      nodules were detected with at least one modality (radiologists in consensus, CAD,
      85 nodules with diameter < 5 mm, 68 with diameter > or = 5 mm). The results of
      automatic nodule detection were compared to nodules detected with any modality as
      gold standard. Computer-aided diagnosis correctly identified 26 of 59 (38%)
      nodules with diameters > or = 5 mm detected by visual assessment by the
      radiologists; of these, CAD detected 44% (24 of 54) nodules without pleural
      contact. In addition, 12 nodules > or = 5 mm were detected which were not
      mentioned in the radiologist's report but represented real nodules. Sensitivity
      for detection of nodules > or = 5 mm was 85% (58 of 68) for radiologists and 38%
      (26 of 68) for CAD. There were 5.8+/-3.6 false-positive results of CAD per CT
      study. Computer-aided diagnosis improves detection of pulmonary nodules at spiral
      CT and is a valuable second opinion in a clinical setting for lung cancer
      screening despite of its still limited sensitivity.

PMID- 11976847
TI  - Unusual pleural involvement after exposure to amorphous silicates (Liparitosis):
      report of two cases.
AB  - Liparitosis is a rare pneumoconiosis determined by inhalation of pumice, an
      amorphous complex silicate extracted in the quarries of Lipari (Aeolian
      Archipelago, Italy). We describe two cases of subjects occupationally exposed to
      pumice dust in which high-resolution computed tomography (HRCT) revealed the
      presence of pleural lesions without parenchymal involvement.

PMID- 11976848
TI  - Imaging of ischemic heart disease.
AB  - Despite advances in the understanding and treatment of ischemic cardiomyopathy,
      characterized by extensive coronary artery disease and left ventricular (LV)
      dysfunction, the prognosis remains poor with only a 50-60% 5-year survival rate.
      The composition of atherosclerotic lesions is currently regarded as being more
      important than the degree of stenosis in determining acute events. If imaging
      techniques could distinguish vulnerable from stable plaques, then high-risk
      patient subgroups could be identified. Another important concept is that LV
      dysfunction may be the result of either scarring due to necrosis or to the
      presence of myocardial hibernation, in which there is sufficient blood flow to
      sustain viable myocytes, but insufficient to maintain systolic contraction. This
      concept of myocardial viability is critical for making optimal clinical
      management decisions. This review describes how noninvasive imaging methods can
      be used to distinguish regions of irreversibly injured myocardium from viable but
      hibernating segments. Technical advances in CT and MR have made imaging of the
      beating heart possible. Considerable clinical progress has already been made and
      further cardiac applications are expected. Radiologists therefore have new
      opportunities for involvement in cardiac imaging but must recognize the political
      implications as well as the diagnostic potential of these modalities not only for
      the heart, but also for the whole vascular system. This review focuses on imaging
      myocardial injury. It compares state-of-the-art CT and MR with more established
      yet contemporary echocardiography and nuclear scintigraphy.

PMID- 11976849
TI  - Multislice helical CT of the heart with retrospective ECG gating: reduction of
      radiation exposure by ECG-controlled tube current modulation.
AB  - Our objective was to evaluate image quality and radiation exposure of
      retrospectively ECG-gated multislice helical CT (MSCT) investigations of the
      heart with ECG-controlled tube current modulation. One hundred patients underwent
      MSCT scanning (Somatom VolumeZoom, Siemens, Forchheim, Germany) for detection of
      coronary artery calcifications. A continuous helical data set of the heart was
      acquired in 50 patients (group 1) using the standard protocol with constant tube
      current, and in 50 patients (group 2) using an alternative protocol with reduced
      radiation exposure during the systolic phase. The standard deviations (SD) of
      predefined regions of interest (ROIs) were determined as a measure of image noise
      and were tested for significant differences. There was no significant difference
      between group 1 and group 2 with respect to image noise. Radiation exposure with
      and without tube current modulation was 1.0 and 1.9 mSv ( p<0.0001),
      respectively, for males and 1.4 and 2.5 mSv ( p<0.0001), respectively, for
      females; thus, there was a mean dose reduction of 48% for males and 45% for
      females, respectively. The ECG-controlled tube current modulation allows
      significant dose reduction when performing retrospectively ECG-gated MSCT of the
      heart.

PMID- 11976850
TI  - Classification of hypervascularized lesions in CE MR imaging of the breast.
AB  - The purpose of this paper is to define and evaluate a classification category for
      contrast-enhanced (CE) MR imaging of the breast based on the BI-RADS mammographic
      categories of the American College of Radiology. Using five evaluation criteria
      for MR findings (initial signal increase, post-initial signal behavior, shape,
      border, and contrast material distribution within enhancing tumors) 522 patients
      (1031 breasts) were analyzed. Scores were given from 0 to 8 points and classified
      into five categories (group I: 0 points, negative; group II: 1-2 points, benign;
      group III: 3 points, probably benign; group IV: 4-5 points, suspicious
      abnormality; group V: 6-8 points, highly suspicious for malignancy) to 265 focal
      hypervascularized breast lesions in 244 breasts (patient group A). These findings
      were correlated with histology or follow-up. Additionally, this classification
      was correlated to the contrast medium uptake within the parenchyma of the
      remaining 787 breasts without any focal lesion (patient group B). Two hundred
      sixty-five hypervascularized lesions in 238 patients (244 breasts, patient group
      A) were classified into group I: 0%; group II: 27.3%; group III: 22.3%; group IV:
      18.6%; and group V: 31.8%. Histology revealed 115 benign and 134 malignant tumors
      in these groups. Sixteen benign lesions were controlled by follow-up. Sensitivity
      for the detection of malignancy using the presented multifactorial MRM
      classification was 92%, and specificity was 92%. Excluding cases of ductal
      carcinoma in situ specificity increased to 95%. Seven hundred eighty-seven
      breasts without any focal hypervascularized lesion (patient group B) were
      classified into groups I or II. Follow-up ( n=771) or histology ( n=14) confirmed
      the diagnosis in 785 of these breasts. Histopathology revealed, however,
      malignant tumors in the remaining two cases. The classification of lesions based
      on a multifactorial analysis is very helpful in the interpretation of CE MRI of
      the breast. The evaluation of all diagnostic imaging modalities, however, is
      essential in determining the correct diagnosis and/or in deciding on the
      appropriate therapeutic procedure.

PMID- 11976851
TI  - Low-grade mucosa-associated lymphoma of the breast: radiological-pathological
      correlation.
AB  - Primary breast lymphoma generally is a rare disease. We present a case of a low
      grade mucosa-associated (MALT) lymphoma of the breast in a 32-year-old woman, a
      distinctive type of localized non-Hodgkin's lymphoma (NHL), which is very seldom
      located in the breast. We performed differential diagnosis and radiological
      pathological correlation with regard to typical microscopic criteria and clinical
      relevance that apply for that special entity.

PMID- 11976852
TI  - Breast infection due to dirofilariasis.
AB  - We describe a case of dirofilariasis of the breast in a woman presenting with a
      breast lump. The mammogram and ultrasound appearances are described with
      histopathological correlation. The suspicion of a parasitic infection was raised
      by the presence of rod-like structures within a hypoechoic nodule on sonography,
      appearances that have not been previously described. The case illustrates an
      unusual diagnostic problem since it presented in a non-endemic area.

PMID- 11976853
TI  - Atypical evolution of a calcified lipid cyst presenting spontaneously as a
      suspicious cluster of microcalcifications.
AB  - We report an infrequent mammographic case in which a gross-calcified lipid cyst
      evolved spontaneously to form a cluster of pleomorphic microcalcifications which
      were indistinguishable from those seen in breast cancer. The biopsy performed was
      consistent with fat necrosis. Ultrasonography of the specimen showed a nodule
      with mixed echogenicity surrounded by a hypoechoic rim. To our knowledge, this
      behavior is extremely rare, with only one similar case reported in the
      literature.

PMID- 11976854
TI  - Lymph node metastases from head and neck squamous cell carcinoma: MR imaging with
      ultrasmall superparamagnetic iron oxide particles (Sinerem MR) -- results of a
      phase-III multicenter clinical trial.
AB  - The aim of this study was to compare the clinical usefulness of ultrasmall
      superparamagnetic iron oxide (USPIO) MR contrast media (Sinerem, Guerbet
      Laboratories, Aulnay-sous-Bois, France) with precontrast MRI in the diagnosis of
      metastatic lymph nodes in patients with head and neck squamous cell carcinoma,
      using histology as gold standard. Eighty-one previously untreated patients were
      enrolled in a multicenter phase-III clinical trial. All patients had a
      noncontrast MR, a Sinerem MR, and surgery within a period of 15 days. The MR
      exams were analyzed both on site and by two independent radiologists (centralized
      readers). Correlation between histology and imaging was done per lymph node
      groups, and per individual lymph nodes when the short axis was > or = 10 mm. For
      individual lymph nodes, Sinerem MR showed a high sensitivity (> or = 88%) and
      specificity (> or = 77%). For lymph node groups, the sensitivity was > or = 59%
      and specificity > or = 81%. False-positive results were partially due to
      inflammatory nodes; false-negative results from the presence of undetected
      micrometastases. Errors of interpretation were also related to motion and/or
      susceptibility artifacts and problems of zone assignment. Sinerem MR had a
      negative predictive value (NPV) > or = 90% and a positive predictive value (PPV)
      > or = 51%. The specificity and PPV of Sinerem MR were better than those of
      precontrast MR. Precontrast MR showed an unexpectedly high sensitivity and NPV
      which were not increased with Sinerem MR. The potential contribution of Sinerem
      MR still remains limited by technical problems regarding motion and
      susceptibility artifacts and spatial resolution. It is also noteworthy that
      logistical problems, which could reduce the practical value of Sinerem MR, will
      be minimized in the future since Sinerem MR alone performed as good as the
      combination of precontrast and Sinerem MR.

PMID- 11976855
TI  - Use of electrical impedance scanning in the differentiation of sonographically
      suspicious and highly suspicious lymph nodes of the head-neck region.
AB  - Sonographic differentiation between inflammatory and malignant lymph nodes is
      difficult, due in part to almost unchanged morphology of small lymph node
      metastases; however, as cancer cells exhibit altered dielectric properties,
      measurement of local electrical field distortions may be useful as adjunct to
      ultrasound in detection of malignancy. In this study, we evaluated the ability of
      electrical impedance scanning (EIS) to differentiate cervically located
      sonographically suspicious or highly suspicious lymph nodes. Seventy patients
      with 106 sonographically suspicious lymph nodes (mean size 20 x 13 x 13 mm, mean
      depth 8 mm) were examined using TransScan TS2000 (Siemens, Erlangen, Germany;
      manufactured by TransScan Research and Development Co., Israel). Included in the
      study were cervical ( n=64), inframandibular/periparotideal ( n=32) and
      nuchal/supraclavicular ( n=10) nodes. The EIS results were compared with
      histopathological ( n=100) and serological ( n=6) findings. Sixty-two of 64
      malignant lymph nodes were correctly detected using EIS; 19 of 42
      inflammatory/benign lymph nodes were correctly identified as benign (true
      positive 96.9%, true negative 45.2%; accuracy 71.3%, negative predictive value
      90.5%, positive predictive value 59.6%). The high tumour detection rate achieved
      in this study suggests that EIS may be of value as an adjunctive technique in
      differentiation of lymph nodes of the head-neck region. Software changes to
      reduce the high number of false-positive markers are, however, necessary to
      improve the value in the evaluation during a regular clinical routine.

PMID- 11976856
TI  - Contrast-enhanced MR imaging of the endolymphatic sac in patients with sudden
      hearing loss.
AB  - Our objective was to evaluate the frequency of contrast enhancement of the
      endolymphatic sac in patients with sudden hearing loss. Forty consecutive
      patients with sudden sensorineural hearing loss (20 males and 20 females; age
      range 11-82 years), 40 age-matched control subjects, and 5 patients with
      Meniere's disease were examined using the same imaging protocol on a 1.5-T MR
      system. Pre- and post-contrast-enhanced T1-weighted 3D spoiled gradient-echo
      sequence (3D SPGR; TR/TE=23/10 ms, no. of excitations=1, flip angle=30 degrees)
      images were obtained using a voxel size of 0.6 x 0.7 x 0.8 mm(3). Contrast
      enhancement in the area of the endolymphatic sac was assessed by two
      radiologists, and the frequency of contrast enhancement was compared between the
      three study groups. Enhancement of the ipsilateral endolymphatic sac was observed
      in 30 of the 40 patients with sudden hearing loss (75%). Twenty of these 30
      patients also showed enhancement on the contralateral side, and 1 patient showed
      enhancement only on the contralateral side. Only 1 of the 5 patients with
      Meniere's disease showed enhancement. Nine of the 40 control subjects (22.5%)
      showed enhancement (bilateral enhancement in 5 subjects, unilateral in 4). The
      frequency of enhancement in patients with sudden hearing loss was significantly
      higher than that in control subjects ( P<0.0001) or patients with Meniere's
      disease ( P<0.05). The frequency of contrast enhancement of the endolymphatic sac
      is significantly increased in patients with sudden hearing loss, but further
      study is necessary to clarify the relationship between this finding and the
      pathophysiology of sudden hearing loss.

PMID- 11976857
TI  - The value of magnetic resonance imaging in the diagnosis of orbital floor
      fractures.
AB  - The value of MRI in the diagnosis of acute orbital floor fractures has not been
      clearly defined. We therefore compared MR findings with CT findings in patients
      with orbital trauma. In 30 patients with isolated orbital trauma both coronal CT
      and coronal MRI were used to examine the orbits and the adjacent paranasal
      sinuses. Visualization of anatomical landmarks, the kind and extent of traumatic
      lesions, as well as artifacts were scored. The scores were compared using the
      Wilcoxon matched-pairs signed-rank test. Interexamination agreement between the
      two methods was calculated using a kappa analysis. All examinations had
      diagnostic quality: 30 fractures of the orbital floor (9 right and 21 left
      orbital floor fractures) were identified. In addition, CT showed fractures of the
      medial orbital wall in 19 patients (63.3%), of the lateral wall in 10 patients
      (33.3%), of the zygomatic arch in 2 patients (6.7%), and of the maxillary sinus
      in 4 patients (13.3%). Soft tissue herniation was shown in 13 patients (inferior
      rectus muscle twice, orbital fat in 11 cases). Magnetic resonance imaging
      demonstrated soft tissue herniation in 21 patients: muscle in 4, orbital fat in
      17 cases. Magnetic resonance imaging is able to demonstrate orbital floor
      fractures as sensitively as CT, but CT is superior to MRI in showing small and
      associated fractures; therefore, CT remains in orbital fractures the imaging
      modality of choice. Magnetic resonance imaging is superior to CT in showing soft
      tissue herniations; therefore, MRI may have a role as an adjunct to CT if soft
      tissue entrapment remains unclear.

PMID- 11976858
TI  - Multifocal fibrosclerosis: a new case report and review of the literature.
AB  - A case of multifocal fibrosclerosis is presented with MR images. Bilateral
      sclerosing orbital pseudotumor invading cavernous sinuses were the presenting
      disorder. Magnetic resonance imaging showed involvement of paranasal sinuses
      bilaterally and multiple supratentorial dural masses. Retroperitoneal fibrosis
      was associated with the condition. Multifocal involvement should be considered in
      patients with sclerosing orbital pseudotumor and an imaging approach should be
      performed on the appropriate clinical condition to document possible coexistence
      of other disorders including retroperitoneal fibrosis, mediastinal fibrosis,
      sclerosing cholangitis, and Riedel's thyroiditis

PMID- 11976859
TI  - Morphological findings in dynamic swallowing studies of symptomatic patients.
AB  - The aim of this study was to assess the role of videofluoroscopy in the detection
      of structural abnormalities of the pharynx and esophagus in patients with
      different symptoms of impaired deglutition. Dynamic radiographic recording of
      deglutition was performed in 3193 consecutive patients (1578 men, 1615 women;
      mean age 54 years) suffering from dysphagia, suspicion of aspiration, globus
      sensation, and non-cardiac chest pain. We assessed different structural lesions
      from the oral cavity to the esophagus and classified them into eight categories.
      Their frequency and association with the different clinical symptoms were
      evaluated. Videofluoroscopy revealed 1040 structural abnormalities in 833
      patients (26%) including mass lesions from the oral cavity to hyoid/larynx (
      n=66), pharyngeal diverticula ( n=181), pharyngeal masses ( n=78), other
      pharyngeal narrowings ( n=71), webs ( n=98), masses ( n=39), and other narrowings
      ( n=73) of the upper esophageal sphincter, esophageal diverticula ( n=80),
      esophageal webs, rings and strictures ( n=194), and intrinsic and extrinsic
      esophageal lesions ( n=160). There was a considerable variance of findings for
      different symptoms. In a large proportion of symptomatic patients
      videofluoroscopy detects morphological abnormalities along pharynx and esophagus
      often combined with functional disorders. This fact underlines the role of
      videofluoroscopy as a diagnostic test for function as well as morphology.

PMID- 11976861
TI  - Transhepatic intravascular ultrasound for evaluation of portal venous involvement
      in patients with cancer of the pancreatic head region.
AB  - The aim of this study was to evaluate the ability of intravascular ultrasound to
      diagnose tumor involvement of the portal and the superior mesenteric veins using
      the preoperative percutaneous, transhepatic approach, and to compare the findings
      with those made at concomitant direct portography, surgery, and histopathological
      examination. Ten patients with a preoperative diagnosis of a resectable tumor in
      the pancreatic head region were examined with percutaneous transhepatic
      portography (PTP) and intravascular ultrasound (IVUS). The surgeon's
      intraoperative evaluation and the histopathological examination in combination
      revealed tumor involvement of the portal or superior mesenteric veins in six of
      the ten patients. Percutaneous transhepatic portography suggested tumor
      involvement of the veins in six patients but two of the examinations were false
      positive and another two were false negative. Intravascular ultrasound showed
      signs of tumor involvement in eight patients. The examination was, however, false
      positive in two patients, but there were no false negatives. Complications of the
      percutaneous transhepatic procedure occurred in six patients including severe
      pain, bleeding, and related death. Percutaneous transhepatic IVUS of the portal
      vein may be a useful tool in the preoperative selection of the subgroup of
      patients with tumor of the pancreatic head region that could benefit from
      surgery. There is a need for technical improvement as well as studies with larger
      patient series to definitely decide the role of the technique.

PMID- 11976860
TI  - Colonic diverticulitis: impact of imaging on surgical management -- a prospective
      study of 542 patients.
AB  - The aim of this study was to compare the performance of the CT and the water
      soluble contrast enema (CE) in the diagnosis and the severity of acute left
      colonic diverticulitis, and to recognize the impact of CT during the acute phase
      and after a first acute episode successfully treated medically. From 1986 to
      1997, all patients admitted in our emergency center with clinically suspected
      left-colonic diverticulitis had a CE and a CT within 72 h of their admission,
      unless clinical findings required immediate laparotomy. They were prospectively
      included in the study if one or both radiological exams showed signs of acute
      diverticulitis and/or diverticulitis was surgically removed and histologically
      proven. Diverticulitis was considered moderate when CT showed localized
      thickening of the colonic wall (5 mm or more) and inflammation of pericolic fat
      and CE showed segmental lumen narrowing and tethered mucosa; it was considered
      severe when abscess and/or extraluminal air and/or contrast were observed on CT
      and when one or both of the latter signs were seen on CE. Five hundred forty-two
      patients entered the study; 465 patients (86%) had a CT exam, 439 (81%) had a CE,
      and 420 (77%) had both exams. The performance of CT is significantly superior to
      CE in terms of sensitivity (98 vs 92%, p<0.01), and in the evaluation of the
      severity of the inflammation (26 vs 9%, p<0.02). Moreover, of 69 patients who had
      an associated abscess seen on CT, only 20 (29%) had indirect signs of this
      complication on CE. During the acute phase the chances of medical treatment
      failure are statistically greater when diverticulitis is considered severe on CT
      than when it is considered moderate (26% for the severe diverticulitis vs 4% for
      the moderate ones, p<0.0001). After successful medical treatment of the acute
      episode, patients with severe diverticulitis on the CT had statistically greater
      incidence of secondary bad outcome than patients with moderate diverticulitis (36
      vs 17%, p<0.0001). Computed tomography should be preferred to CE as the initial
      radiological exam of diverticulitis because of its statistically significant
      superiority in sensitivity and for its statistically much higher performance in
      the detection of severe infection, especially when an abscess is associated with
      the disease. The severity of diverticulitis on CT is statistically predictive of
      the risk of medical treatment failure during the acute phase and of the chances
      of bad secondary outcome after a successful medical treatment of the first
      episode.

PMID- 11976862
TI  - Multislice CT cholangiography without biliary contrast agent: technique and
      initial clinical results in the assessment of patients with biliary obstruction.
AB  - Our objective was to describe our technique for multislice CT cholangiography
      without cholangiographic contrast agent, and to present our preliminary clinical
      results. Thirty-seven patients with suspected biliary obstruction were studied. A
      multislice CT unit was used with the following technical parameters: 2.5-mm
      collimation; 7.5-mm/s table speed; pitch 6; 0.8-s rotation time; 300 mA; 120 kVp;
      18- to 24-s scan time; scan volume ranging from the hepatic dome to below the
      pancreatic head; 70-s delay after injection of 150 ml of iodinated contrast agent
      at 4 ml/s. No biliary contrast material was given; oral iodinated contrast agent
      was administered to opacify bowel loops. Axial, multiplanar reformatted, and
      minimum intensity projection images were evaluated. The CT findings were compared
      with the gold standard techniques: endoscopic retrograde cholangiography (ERCP)
      in 30 patients, percutaneous transhepatic cholangiography in 5, and
      intraoperative cholangiography in 2. In 5 patients with ampullary lesions biopsy
      was made during ERCP, 9 underwent surgery, and 11 US-guided fine-needle
      aspiration. Bile ducts appeared hypodense within the surrounding enhanced
      structures. Regarding the site of obstruction, agreement between multislice CT
      and conventional cholangiography was observed in all cases. One patient presented
      negative findings on both CT and ERCP. In 31 of 36 (86%) patients, multislice CT
      cholangiography without cholangiographic contrast agent correctly assessed the
      cause of bile duct obstruction. Multislice CT cholangiography without
      cholangiographic contrast agent seems to be a promising diagnostic tool in the
      assessment of patients with bile duct obstruction.

PMID- 11976863
TI  - Pitfalls in liver imaging.
AB  - Localized, abnormal attenuation/intensity areas on unenhanced and/or enhanced
      study of CT/MR imaging do not necessarily correspond to tumors themselves or real
      tumor size. Pitfalls in the diagnosis of liver tumor are described dividing into
      enhanced study (vascular variants, vascular abnormalities, hyperplastic nodules,
      around the tumor, and miscellaneous) and unenhanced study (fatty change, focal
      spared area of diffuse fatty liver, and miscellaneous).

PMID- 11976864
TI  - Detection of portal venous gas on sonography, but not on CT.
AB  - We report three cases of portal venous gas detected on sonography without any
      portal abnormality on CT. In such a situation portal gas could correspond to a
      tiny amount of intraluminal gas after blunt abdominal trauma or, in contrast, to
      large or very large quantities of high blood-solubility gases in case of
      septicemia. Outcome was favorable in all three cases.

PMID- 11976865
TI  - Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional
      therapy.
AB  - Non-occlusive mesenteric ischemia (NOMI) compromises all forms of mesenteric
      ischemia with patent mesenteric arteries. It generally affects patients over 50
      years of age suffering from myocardial infarction, congestive heart failure,
      aortic insufficiency, renal or hepatic disease and patients following cardiac
      surgery. Non-occlusive disease accounts for 20-30% of all cases of acute
      mesenteric ischemia with a mortality rate of the order of 50%. Acute abdominal
      pain may be the only early presenting symptom of mesenteric ischemia. Non
      invasive imaging modalities, such as CT, MRI, and ultrasound, are able to
      evaluate the aorta and the origins of splanchnic arteries. Despite the technical
      evolution of those methods, selective angiography of mesenteric arteries is still
      the gold standard in diagnosing peripheral splanchnic vessel disease. In early
      non-occlusive mesenteric ischemia, as opposed to occlusive disease, there is no
      surgical therapy. It is known that mesenteric vasospasm persists even after
      correction of the precipitating event. Vasospasm frequently responds to direct
      intra-arterial vasodilator therapy, which is the only treatment that has been
      shown to be effective.

PMID- 11976866
TI  - Percutaneous peritoneovenous shunt positioning: technique and preliminary
      results.
AB  - Nine peritoneovenous shunts were positioned by percutaneous technique in seven
      patients with advanced malignancy causing severe refractory ascites, and in two
      patients with hepatic cirrhosis (one with hepatocarcinoma). In all patients the
      shunts were percutaneously placed through the subclavian vein in the angiographic
      suite under digital fluoroscopic guide. No complications directly related to the
      procedure occurred. The shunt was successfully positioned in all patients in 60
      min average time. No patient showed symptoms related to pulmonary overload or to
      disseminated intravascular coagulation. All patients had a significant
      improvement of the objective symptoms related to ascites such as respiratory
      symptoms, dyspepsia, and functional impairment to evacuation describing an
      improvement of their quality of life. Maximum shunt patency was 273 days.
      Percutaneous placement of peritoneovenous shunt is a safe, fast, and inexpensive
      procedure, extremely useful in resolution of refractory ascites, reducing
      symptoms, and allowing effective palliation, with a great improvement in quality
      of life.

PMID- 11976867
TI  - Imaging of chronic posttraumatic osteomyelitis.
AB  - Posttraumatic osteomyelitis is frequently characterized by chronicity and
      recurrent activation of infection. The diagnosis is usually made on the basis of
      clinical, laboratory, and imaging examinations. The conventional radiograph is
      the basic imaging study that provides important information about skeletal
      deformity, bone quality, identification of metallic implants, and consolidation
      of the former fracture site. Other imaging techniques are required to determine
      the grade of activity, to define the extent of infection and to delineate small
      sequestra, intraosseus fistula and abscesses. A variety of more sophisticated
      modalities, such as modern cross-sectional imaging and radionuclide studies, are
      available, and the decision to choose the most suitable method can be very
      difficult. This review gives an overview of definition, epidemiology, and
      pathophysiology of chronic posttraumatic osteomyelitis and discusses the value of
      currently used imaging modalities.

PMID- 11976869
TI  - Supraspinatus tendon tears: comparison of US and MR arthrography with surgical
      correlation.
AB  - The aim of this study was to compare the diagnostic reliability of US with MR
      arthrography in diagnosing supraspinatus tendon tears. Surgical findings were
      used as the gold standard in detecting tears. A total of 44 patients were
      assessed with transverse and longitudinal US scans with respect to the long axis
      of the rotator cuff tendons and then examined with MR arthrography. This
      technique involved free-hand injection of contrast medium into the shoulder
      joint. At surgery 20 incomplete and 24 complete tears were observed. Ultrasound
      offered good results for the large tears, but its sensitivity decreased
      proportionally with the size of the tears. Magnetic resonance arthrography
      correctly diagnosed 43 tears, whereas only one false-negative diagnosis of
      tendinosis was made for a partial tear on the bursal side. Since it improves the
      diagnosis of small tears, MR arthrography must be performed on all patients for
      whom surgical repair is necessary in order to restore normal functions.

PMID- 11976868
TI  - MRI of the wrist and finger joints in inflammatory joint diseases at 1-year
      interval: MRI features to predict bone erosions.
AB  - The aim of this study was to assess the ability of MRI determined synovial
      volumes and bone marrow oedema to predict progressions in bone erosions after 1
      year in patients with different types of inflammatory joint diseases. Eighty-four
      patients underwent MRI, laboratory and clinical examination at baseline and 1
      year later. Magnetic resonance imaging of the wrist and finger joints was
      performed in 22 patients with rheumatoid arthritis less than 3 years (group 1)
      who fulfilled the American College of Rheumatology (ACR) criteria for rheumatoid
      arthritis, 18 patients with reactive arthritis or psoriatic arthritis (group 2),
      22 patients with more than 3 years duration of rheumatoid arthritis, who
      fulfilled the ACR criteria for rheumatoid arthritis (group 3), and 20 patients
      with arthralgia (group 4). The volume of the synovial membrane was outlined
      manually before and after gadodiamide injection on the T1-weighted sequences in
      the finger joints. Bones with marrow oedema were summed up in the wrist and
      fingers on short-tau inversion recovery sequences. These MRI features was
      compared with the number of bone erosions 1 year later. The MR images were scored
      independently under masked conditions. The synovial volumes in the finger joints
      assessed on pre-contrast images was highly predictive of bone erosions 1 year
      later in patients with rheumatoid arthritis (groups 1 and 3). The strongest
      individual predictor of bone erosions at 1-year follow-up was bone marrow oedema,
      if present at the wrist at baseline. Bone erosions on baseline MRI were in few
      cases reversible at follow-up MRI. The total synovial volume in the finger
      joints, and the presence of bone oedema in the wrist bones, seems to be
      predictive for the number of bone erosions 1 year later and may be used in
      screening. The importance of very early bone changes on MRI and the importance of
      the reversibility of these findings remain to be clarified.

PMID- 11976870
TI  - Validation of the Ottawa knee rules in an emergency teaching centre.
AB  - Our objective was to determine the value of the Ottawa knee rules when applied by
      users with different levels of clinical training. We used a prospective patient
      survey by the medical students and surgery residents of a European university
      trauma centre. The study group consisted of 261 eligible patients who presented
      with acute knee trauma during a 6-month period. Radiography or follow-up was
      obtained for each patient. Data were separately analysed according to the degree
      of qualification of the initial examiner. The Ottawa knee rules had a sensitivity
      and a negative predictive value of 1.00. Variable degree of medical competence of
      the users did not alter the accuracy of the rules. Application of the rules would
      have reduced knee radiography requests by 25%. The Ottawa knee rules remain
      highly sensitive when applied by medical users with different levels of
      qualification, such as encountered in a teaching setting.

PMID- 11976871
TI  - Magnetic resonance imaging of injected silicone: findings in seven male-to-female
      transsexuals.
AB  - Our goal was to describe the MR findings of subcutaneously injected silicone in
      male-to-female transsexuals and to determine the most optimal combination of
      pulse sequences for discrimination of injected silicone from the surrounding
      structures. Seven male-to-female transsexuals were referred for MRI in order to
      detect the injected silicone in the subcutaneous tissues and to visualize distant
      migration and possible complications. Conventional spin-echo (SE) T1-weighted and
      turbo SE proton-density/T2-weighted, plain short tau inversion recovery (STIR),
      and two STIR sequences with, respectively, water and silicone suppression were
      applied at 1.5 T. Three observers trained in MRI analysed the images separately
      for the abnormalities and rated the images using a four-level scale. The STIR
      with water suppression provided the highest contrast between silicone and the
      surrounding adipose tissue. Silicone-specific STIR pulse sequences provided clear
      images for the evaluation of the amount and patterns of local and distant spread
      of injected fluid silicone. Magnetic resonance imaging readily identifies the
      subcutaneously injected silicone, its distant migration and the amount of tissue
      disorganization around the silicone deposits. Two silicone-specific STIR
      sequences are usually sufficient for imaging the spread of silicone.

PMID- 11976872
TI  - Quiz case of the month. Internal iliac aneurysm.

PMID- 11976877
TI  - Identification of Cytokinin Biosynthesis Genes in Arabidopsis: A Breakthrough for
      Understanding the Metabolic Pathway and the Regulation in Higher Plants.
AB  - The primary biosynthetic reaction of cytokinin is thought to be the
      isopentenylation of an adenine nucleotide such as AMP with
      dimethylallylpyrophosphate. For many years, the nature of the enzyme catalyzing
      this reaction in higher plants had not been identified despite the physiological
      importance of these compounds. However, the completion of the genomic sequence of
      Arabidopsis thaliana, a model plant for genetic research, has provided us with
      new opportunities to solve these problems. Recent studies have revealed the
      cytokinin biosynthesis enzyme is encoded by a small multigene family that is
      structurally related to both bacterial adenylate isopentenyltransferase and tRNA
      isopentenyltransferase. Interestingly, biochemical studies of some of the gene
      products indicate that ADP and ATP, rather than AMP, are preferentially used as
      substrates for this biosynthetic reaction. These findings require reconsideration
      of the currently accepted cytokinin biosynthetic pathway. In addition, there is
      an increasing body of evidence suggesting that the expression of these cytokinin
      synthesis genes is affected by the availability of nutrients.

PMID- 11976879
TI  - Folke K. Skoog: In Memory and Tribute.

PMID- 11976878
TI  - Structural Requirements of Abscisic Acid (ABA) and its Impact on Water Flow
      During Radial Transport of ABA Analogues Through Maize Roots.
AB  - The effect of (+) (ABA) and (?)-abscisic acid and nine ABA metabolites,
      precursors or derivatives on radial water movement through maize roots, was
      investigated using a suction technique (Freundl and others 1998). (+)-ABA, (+)-
      and (?)-abscisyl aldehyde, (+)-8?-hydroxymethyl ABA, (+)-8?-methylene, and (+)-8?
      acetylene ABA stimulated radial water transport. (?)-ABA, phaseic acid, and (+)
      8?-acetylene methyl ABA were ineffective. ELISA analysis for ABA detected and
      apparent increase of free ABAxyl in xylem sap of excised root systems that were
      perfused with either (+)-abscisyl aldehyde, (+)-8?-methylene, (+)8?-acetylene
      ABA, or ABA-glucose ester. The analogues (+)-8?-hydroxymethyl ABA and (?)
      abscisyl aldehyde passed the cortex of maize roots without changing the ABAxyl.
      The data from this study permit conclusions about the structural requirements for
      hormonal regulation of hydraulic conductivity.

PMID- 11976880
TI  - Discoveries and Dilemmas Concerning Cytokinin Metabolism.
AB  - Natural cytokinin compounds that function as plant hormones are adenine molecules
      connected to an N6 side chain. Metabolic pathways produce various structural
      modifications to the adenine moiety and/or the side chain that affect cytokinin
      function, activity, stability, and transport in plants. This review focuses on
      recent research that is elucidating the genes and biochemical pathways involved
      in cytokinin conjugation, deconjugation, and interconversion. One area of new
      discovery concerns the process of O-glucoside conjugate formation. Genes have
      been identified for O-glucosyltransferase enzymes in Phaseolus (ZOG1 and ZOX1)
      and maize (cisZOG1) and have been used to study enzyme activity, structure, and
      function in plant development. New information about the genetic basis of the
      adenine salvage pathway and its relationship to cytokinin interconversion and
      regulation has also become available. However, various dilemmas about cytokinin
      metabolism remain and need to be resolved using a combination of research
      approaches.

PMID- 11976881
TI  - Molecular Mechanisms of Cytokinin Signaling.
AB  - Cytokinins regulate a myriad of plant growth and developmental processes. Recent
      molecular genetic studies in Arabidopsis have begun to unravel the molecular
      mechanisms underlying cytokinin perception and signal transduction. A family of
      cytokinin receptors has been identified, and these are homologous to bacterial
      two-component sensor kinases. Events immediately downstream of cytokinin binding
      are similar to the classic phosphorelay paradigm. The cytokinin signal appears to
      be transduced from the membrane-localized histidine kinase-like receptors into
      the nucleus via a transient translocation of the AHP proteins, which are
      Arabidopsis homologs of histidine phosphotransfer proteins. Once in the nucleus,
      the AHPs activate the type-B class of Arabidopsis response regulators (ARRs),
      which in turn activate the transcription of a second class of Arabidopsis
      response regulators, the type-A ARRs. A model of cytokinin signaling from
      perception at the plasma membrane to activation of gene expression in the nucleus
      is beginning to emerge.

PMID- 11976882
TI  - New Insights into the Functions of Cytokinins in Plant Development.
AB  - Recent breakthroughs in cytokinin research have shed new light on the role of
      cytokinin in plant development. Loss-of-function mutants of a cytokinin receptor
      reveal a role for the hormone in establishment of the vasculature during
      embryonic development. Cytokinin controls the number of early cell divisions via
      a two-component signaling system. Genetically engineered plants that have a
      reduced cytokinin content demonstrate the regulatory role of the hormone in
      control of meristem activity and organ growth during postembryonic development,
      with opposite roles in roots and shoots. There is increasing evidence from work
      with transgenic plants and mutant analysis that cytokinins do not perform the
      previously proposed function as a root-derived signal for the regulation of shoot
      branching. Root-borne cytokinins might serve as a long-range signal controling
      other processes at distant sites, such as responding to nutritional status,
      particularly nitrogen availability.

PMID- 11976883
TI  - Pressure sensation by an anterior pagoda neuron population distributed in
      multiple ganglia in the leech, Whitmania pigra.
AB  - Sensory processing of pressure signals in the central nervous system of the
      leech, Whitmania pigra, was studied through the interaction between pressure
      sensory neurons and anterior pagoda neurons. The responses of anterior pagoda
      neurons to one pulse or a train of pulses in pressure sensory neurons were
      characterized by the latency and amplitude of excitatory postsynaptic potentials.
      Here we show that each pressure sensory neuron is able to activate all the
      anterior pagoda neurons throughout the leech central nervous system. The response
      patterns of all anterior pagoda neurons were appropriate to the pressure
      location: in the longitudinal direction the anterior pagoda neuron further away
      from the pressure sensory neuron had a smaller response with longer latency;
      inside each ganglion, the anterior pagoda neuron on the contralateral side had a
      larger response with shorter latency than that on the ipsilateral side. All
      anterior pagoda neurons excited by pressure sensory neurons comprised a parallel
      system in which each anterior pagoda neuron was independent from the others. The
      location information of pressure stimuli was represented through the response of
      all 40 anterior pagoda neurons covering the whole leech body with a specific
      pattern of latency and amplitude.

PMID- 11976884
TI  - Stimulus size selectivity and receptive field organization of ectostriatal
      neurons in the pigeon.
AB  - The avian ectostriatum is the telencephalic recipient zone of the tectofugal
      pathway, which may be homologous to the colliculo-pulvinar-cortical pathway in
      mammals. The present paper studies the visual response properties and receptive
      field organization of ectostriatal cells in pigeons with extracellular recording
      and computer mapping techniques. The results indicate that 90% of ectostriatal
      cells prefer forward, downward and upward motion of visual stimuli at velocities
      in the range of 16-128 degrees s(-1). They respond optimally to small stimuli (1
      4 degrees visual angle), mostly preferring a target of 2 degrees. Most cells
      (78.8%) have one excitatory receptive field that usually possesses one or two
      hotspots, some cells (13.5%) have two excitatory receptive fields each having one
      or two hotspots, and a few cells (7.7%) have one excitatory receptive field with
      an unresponsive region in the center. An inhibitory receptive field is not found
      surrounding the excitatory receptive field in the ectostriatal cells examined.
      These response properties and receptive field organization may reflect the
      possible roles of the ectostriatum in stimulus discrimination and visual
      cognition.

PMID- 11976885
TI  - Tuning of photoreceptor function in three mantis shrimp species that inhabit a
      range of depths. I. Visual pigments.
AB  - Visual pigments in many animal species, including stomatopod crustaceans, are
      adapted to the photic environments inhabited by that species. However, some
      species occupy a diversity of environments as adults (such as a range of depths
      in the ocean), and a single set of visual pigments would not be equally adaptive
      for all habitats in which individuals live. We characterized the visual pigment
      complements of three species of stomatopod crustaceans, Haptosquilla trispinosa,
      Gonodactylellus affinis, and Gonodactylopsis spongicola, which are unusual for
      this group in that each lives at depths from the subtidal to several tens of
      meters. Using microspectrophotometry, we determined the visual pigments in all
      classes of main rhabdoms in individuals of each species from shallow or deep
      habitats. Each species expressed the typical diversity of visual pigments
      commonly found in stomatopods, but there was little or no evidence of
      differential expression of visual pigments in animals of any species collected
      from different depths. Vision in these species, therefore, is not tuned to
      spectral characteristics of the photic environment by varying the assemblages of
      visual pigments appearing in their retinas.

PMID- 11976886
TI  - Tuning of photoreceptor function in three mantis shrimp species that inhabit a
      range of depths. II. Filter pigments.
AB  - Within single species of stomatopod crustaceans, visual pigment classes of
      homologous photoreceptors throughout the retina are identical in all individuals
      and do not vary with the spectral characteristics of local habitats. We examined
      whether spectral sensitivities of stomatopod photoreceptors are differentially
      tuned through variations in the filter pigments associated with particular
      receptor classes. All classes of intrarhabdomal filters were characterized using
      microspectrophotometry in retinas of three stomatopod species, Haptosquilla
      trispinosa, Gonodactylellus affinis, and Gonodactylopsis spongicola, comparing
      individuals of each species collected from shallow or deep water. Depending on
      the depth of collection, filters varied among individuals both in optical density
      and in spectral shape, and the variation that was observed was similar in all
      three species. The changes in filter density and spectrum increased absolute
      sensitivity in retinas of animals living at greater depths, and tuned their long
      wavelength photoreceptors for improved function in the bluer light available in
      deep water. Plasticity in retinal spectral function may be common in mantis
      shrimp species that occupy a range of habitat depths.

PMID- 11976887
TI  - Spectral sensitivity in a sponge larva.
AB  - Cilia at the posterior pole of demosponge larvae are known to cause directional
      swimming, sometimes in response to light gradients, but so far neither the
      spectral sensitivity of, nor the molecular basis for, this response has been
      investigated. We exploited the fact that the larval cilia respond to sudden
      changes in light intensity, a shadow response, in order to determine the action
      spectrum of photosensitivity. Our results show that larvae of the haplosclerid
      sponge Reniera sp. respond most to blue light (440 nm), and have a smaller,
      secondary response peak to orange-red light (600 nm). These data suggest that the
      photoreceptive pigment in sponge larvae may be a flavin or carotenoid.

PMID- 11976888
TI  - Spatial control of photomechanical movements in the lateral eye of the American
      horseshoe crab, Limulus polyphemus.
AB  - This study asks whether photomechanical movements in the retinal cells of the
      lateral eye of the American horseshoe crab, Limulus polyphemus, are controlled
      locally within each ommatidium, or whether they are a retinal array property
      involving lateral communication between ommatidia. Three experiments were
      performed. A small spot, a vertical slit down the center, or the anterior third
      of an otherwise masked eye was illuminated. The contralateral eye was fully
      illuminated in each experiment and served as a light-adapted control.
      Morphometric analyses of aperture length and rhabdom dimensions were made from
      serial 1-microm plastic sections. The results suggest there is a different
      spatial threshold for photomechanical movement for aperture lengthening than for
      rhabdom lengthening. When only a few ommatidia are illuminated, the aperture does
      not change. When about 10% are illuminated, they lengthen, but the masked
      ommatidia do not. When about a third are illuminated, all the ommatidia in the
      eye lengthen together, including the two thirds that were masked. When either
      only a few ommatidia or about 10% of the ommatidia are illuminated, rhabdom shape
      is unchanged. When a third of the eye is illuminated, the illuminated rhabdoms
      lengthen, but the masked rhabdoms do not.

PMID- 11976889
TI  - A specialized dorsal rim area for polarized light detection in the compound eye
      of the scarab beetle Pachysoma striatum.
AB  - Many animals have been shown to use the pattern of polarized light in the sky as
      an optical compass. Specialised photoreceptors are used to analyse this pattern.
      We here present evidence for an eye design suitable for polarized skylight
      navigation in the flightless desert scarab Pachysoma striatum. Morphological and
      electrophysiological studies show that an extensive part of the dorsal eye is
      equivalent to the dorsal rim area used for polarized light navigation in other
      insects. A polarization-sensitivity of 12.8 (average) can be recorded from cells
      sensitive to the ultraviolet spectrum of light. Features commonly known to
      increase the visual fields of polarization-sensitive photoreceptors, or to
      decrease their spatial resolution, are not found in the eye of this beetle. We
      argue that in this insect an optically unspecialised area for polarized light
      detection allows it not be used exclusively for polarized light navigation.

PMID- 11976891
TI  - Both shared and specialized spinal circuitry for scratching and swimming in
      turtles.
AB  - In principle, nervous systems could generate a behavior either via neurons that
      are relatively specialized for producing one behavior or via multifunctional
      neurons that are shared among multiple, diverse behaviors. I recorded
      extracellularly from individual turtle spinal cord neurons while evoking hindlimb
      scratching, swimming, and withdrawal motor patterns. The majority of spinal
      neurons recorded were activated during both scratching and swimming motor
      patterns, consistent with the existence of shared circuitry for these types of
      limb movements. These neurons tended to have a similar degree of rhythmic
      modulation of their firing rate and a similar phase preference within the hip
      flexor activity cycle during scratching and swimming motor patterns. In addition,
      a substantial minority of neurons were activated during scratching motor patterns
      but silenced during swimming motor patterns. This raises the possibility that
      inhibitory interactions between some scratching and swimming neural circuitry
      play a role in motor pattern selection. These scratch-specialized neurons were
      also less likely than the putative shared neurons to be activated during
      withdrawal motor patterns. Thus, these neurons may represent two separate
      classes, one of which is used generally for hindlimb motor control and the other
      of which is relatively specialized for a subset of hindlimb movement types.

PMID- 11976890
TI  - Amphibious auditory responses of the American alligator (Alligator
      mississipiensis).
AB  - Animals that thrive both on land and underwater are faced with the task of
      interpreting stimuli in different media. This becomes a challenge to the sensory
      receptors in that stimuli (e.g., sound, motion) may convey the same type of
      information but are transmitted with different physical characteristics. We used
      auditory brainstem responses to examine hearing abilities of a species that makes
      full use of these two environments, the American alligator (Alligator
      mississipiensis). In water, alligators responded to tones from 100 Hz to 2,000
      Hz, with peak sensitivity at 800 Hz. In air, they responded to tones from 100 Hz
      to 8,000 Hz, with peak sensitivity around 1,000 Hz. We also examined the
      contribution to hearing of an air bubble that becomes trapped in the middle ear
      as the animal submerges. This bubble has been previously implicated in underwater
      hearing. Our studies show that the trapped air bubble has no affect on auditory
      thresholds, suggesting the bubble is not an important adaptation for underwater
      hearing in this species.

PMID- 11976892
TI  - The light sensitivity of the human visual system depends on the direction of
      view.
AB  - The near-stable North-South orientation of the natural geomagnetic field provides
      an ideal basis for navigation. Sailors have used it since ancient times, animals
      for much longer. Various mechanisms have developed for this purpose. Experiments
      have pointed to a connection between orientation in the geomagnetic field and
      light perception. Such observations are supported by theoretical considerations.
      The underlying interaction should also modulate the light sensitivity of the
      visual system. Recently we demonstrated the effect of an oscillating field. Here
      we report the existence of a weak influence of the static field on visual
      sensitivity in man. By comparison with control experiments, if the directions of
      view line and field vector coincide the perception threshold of a light stimulus
      is slightly but significantly increased. This significance is lost if the view
      line deviates by 10 degrees from the field direction.

PMID- 11976893
TI  - A species-specific frequency filter through specific inhibition, not specific
      excitation.
AB  - Many bushcrickets produce specific song spectra for acoustic communication. Song
      detection and/ or recognition may make use of such specificity. Where in the
      nervous system are the filters for song frequency situated? A peripheral tuning
      for song frequency typically does not exist. Auditory receptor cells of
      bushcrickets connect to local and ascending neurons in the prothoracic ganglion.
      One of the ascending neurons (1) may function as a frequency filter in a group of
      four related bushcrickets (genera Ancistrura, Barbitistes). The frequency
      response of ascending neuron 1 is species-specific roughly corresponding to the
      frequency of the conspecific male song. The species-specific tuning of the neuron
      is not brought about by specific excitation, but by specific inhibition. By
      eliminating this frequency-dependent and species-specific inhibition the former
      filter neuron is transformed into an unspecific broad-band neuron in all four
      species. Its tuning then does not differ from omega neuron 1, a local neuron
      which is rather unspecific for frequency. Also, the supra-threshold responses of
      ascending neuron 1, which are different in intact animals, are similar to each
      other and similar to omega neuron 1 following elimination of inhibition. Only
      ascending neuron 1 of Ancistrura retains some species-specific features at low
      frequencies. In conclusion, evolution changed inhibition, not excitation of a
      species-specific neuron.

PMID- 11976895
TI  - Combined expression of p53, Bcl-2, and p21WAF-1 proteins in lung cancer and
      premalignant lesions: association with clinical characteristics.
AB  - We examined p53, p21WAF-1, and Bcl-2 protein expression in malignant and
      nonmalignant bronchial specimens obtained during bronchoscopy from 60 lung cancer
      patients. Twenty-six (43.3%), 36 (60%), and 20 (33.3%) of the tumors were p53,
      p21WAF-1, and Bcl-2 positive, respectively. High-level p53 and Bcl-2 expression
      characterized advanced preneoplastic lesions, while hyperplasias, squamous
      metaplasias, and mild dysplasias exhibited low levels of expression. There was no
      difference between early and advanced preneoplastic lesions in the level of
      p21WAF-1, expression. A history of heavy smoking was associated with p21WAF-1,
      expression in preneoplastic lesions (p = 0.022) and tumors (p = 0.032). p53(
      )/p21WAF-1(++)/bcl-2(-) was the only significant independent predictor of lower
      clinical stage (OR: 0.88, p = 0.038). In univariate analysis, survival of NSCLC
      patients was affected by disease stage (p <0.001) and tumor histology (p =
      0.018). While single-protein expression was not associated with prognosis, the
      combined immunophenotype p53(-)/p21WAF-1(++)/bcl-2(-) predicted longer survival
      (p = 0.03). In multivariate analysis, only the TNM stage was found to be a
      prognostic factor for NSCLC. We conclude that p53 and Bcl-2 alterations may
      happen early in bronchial carcinogenesis and that absence of these alterations in
      combination with p21WAF-1, overexpression may be associated with a less
      aggressive tumor behavior.

PMID- 11976894
TI  - Supine hypoxemia following nebulizated salbutamol in patients with chronic airway
      obstruction.
AB  - Inhaled beta-adrenergic agonists can decrease arterial oxygen tension (PaO2). A
      decrease in PaO2 can also be observed with supine posture. We assessed the effect
      on PaO2 of supine posture following salbutamol nebulization inpatients with
      chronic airflow obstruction. Twelve patients (10 males, 2 females mean age 60 yr)
      with FEV1/FVC = 0.65 (mean 0.54) and resting PaO2 = 60 mm Hg while breathing room
      air (mean 76.5 mm Hg) were included in a prospective randomized double-blind
      double crossover study conducted for 2 consecutive days. On each study day, each
      patient successively underwent baseline PaO2 measurement; nebulization of either
      salbutamol (0.5% solution, 1 cm3) or saline; two supervised 30-min periods in the
      supine or seated posture, with PaO2 measurement at the end of each period. PaO2
      values were compared with analysis of variance for repetitive measurements (6
      values for each patient). PaO2 values (mean +/- SD; mm Hg) were similar at
      baseline (day 1: 76.5 +/- 8.1; day 2: 76.6 +/- 8.6), after saline + seated (74.8
      +/- 7.2), after saline + supine (74.9 +/- 7.5), and after salbutamol + seated
      (74.3 +/- 7.3). In contrast, PaO2 after salbutamol + supine (70.8 +/- 10.1) was
      significantly lower than all other values (p <0.05), six patients exhibited large
      PaO2 decreases (from 9 to 21 mm Hg). Hypoxemia induced by the combination of
      nebulized salbutamol and supine posture may represent a potential hazard of
      bronchodilator therapy.

PMID- 11976896
TI  - Distinct roles of osteopontin fragments in the development of the pulmonary
      involvement in sarcoidosis.
AB  - Osteopontin (OPN) is a secreted glycoprotein with cell adhesive and
      chemoattractive functions and is expressed in granulomas of sarcoidosis. It is
      well documented that full-length OPN (F-OPN) is susceptible to proteolytic
      fragmentation resulting in carboxyl-terminal OPN (C-OPN). We have previously
      revealed that C-OPN suppresses cell adhesion mediated by F-OPN. However, the
      implication of F-OPN and C-OPN in the progression of pulmonary involvement in
      sarcoidosis has not yet been elucidated. In this study, we demonstrated that (l)
      OPN was expressed in granulomas of sarcoidosis, (2) plasma F-OPN level in
      patients with sarcoidosis, especially in stage II patients, was significantly
      elevated compared with those of the controls, (3) plasma C-OPN levels in patients
      of stages 0, I, and III were significantly higher than those of the controls, and
      (4) in vitro recombinant F-OPN induces macrophage migration and that C-OPN
      inhibits cell migration mediated by F-OPN. These results suggest that F-OPN may
      promote granuloma formation in sarcoidosis, while C-OPN may suppress it. Thus,
      OPN and its fragment may play distinct roles in the development of sarcoidosis.

PMID- 11976897
TI  - The effect of experimental pleurodesis caused by aluminum hydroxide on lung and
      chest wall mechanics.
AB  - The aim of this study was to evaluate the effect of a chemical sclerosing agent,
      aluminum hydroxide, on pleural remodeling and on respiratory mechanics in rats.
      Saline (2 mL) or aluminum hydroxide [2 mL (0.15 g/mL)] was instilled
      intrapleurally in anesthetized male rats. The animals were studied 7 or 30 days
      after the instillation. Respiratory system, lung, and chest wall elastic,
      resistive, and viscoelastic/inhomogeneous pressures were measured by the end
      inflation occlusion method. We studied the pleural remodeling process by means of
      semiquantitative analysis of the induced inflammation and quantitative analysis
      of the collagen extracellular matrix component. The effects on the underlying
      lung were analyzed morphometrically. Chest wall elastic and viscoelastic
      pressures increased after aluminum hydroxide instillation independent of time
      after instillation. Pleural inflammation was observed 7 days after instillation,
      while pleural adherence with a marked increase in the type I/type III collagen
      ratio was present 30 days after instillation. Histological examination
      demonstrated no differences in lung parenchyma among the groups. In conclusion,
      the present model describes the establishment of pleurodesis by aluminum
      hydroxide, which thwarts the normal chest wall mechanical profile without
      inducing any changes in the underlying lungs. The results were disclosed by both
      mechanical and morphological evaluation of the pleural remodeling.

PMID- 11976898
TI  - Alveolar lymphocytosis in patients with chronic uveitis: relationship to
      sarcoidosis.
AB  - Bronchoalveolar lavage (BAL) is frequently performed in patients with suspected
      ocular sarcoidosis. This study describes the immunogenetical, immunological,
      radiological, and functional features of a subclinical alveolar lymphocytosis
      unrelated to sarcoidosis in patients with chronic uveitis. Two hundred and ten
      patients with chronic uveitis of unknown origin, who underwent fiber-optic
      bronchoscopy with BAL as part of a prospective protocol over a three-year period,
      were evaluable for retrospective analysis. Sixty-five patients had alveolar
      lymphocytosis: Sarcoidosis was diagnosed in 13 (6%) patients, whereas alveolar
      lymphocytosis was considered unrelated to sarcoidosis in 52 (25%). Alveolar
      lymphocytosis unrelated to sarcoidosis was not associated with radiologically
      detectable interstitial lung disease or pulmonary function impairment. CD4/CD8
      lymphocyte ratio was 3.7 +/- 3.0. Total cell count, total lymphocyte, and CD4
      lymphocyte percentage were significantly lower when compared with sarcoidosis
      related alveolitis (129,000 +/- 80,000 vs. 218,000 +/- 117,000, p <0.05; 33.1% +/
      13.2 vs. 39.7% +/- 13.2, p <0.05; and 54.3% +/- 18.2 vs. 65.4% +/- 10.1, p
      <0.05, respectively). Patients with alveolar lymphocytosis unrelated to
      sarcoidosis were older (47.8 +/- 17.7 years vs. 42.7 +/- 14.2 years, p <0.05) and
      more likely to carry the HLA-B51 allele (19.7% vs. 7.1%, p <0.01) than patients
      with chronic uveitis without alveolar lymphocytosis. They did not appear to be at
      risk of developing clinically apparent interstitial lung disease on followup. We
      conclude that alveolar lymphocytosis is frequently observed in patients with
      chronic uveitis. It is generally unrelated to sarcoidosis and may then be
      associated with a distinctive immunogenetic phenotype.

PMID- 11976899
TI  - Oxygen-induced pulmonary injury in gamma-glutamyl transpeptidase-deficient mice.
AB  - We used mice with a targeted disruption in g-glutamyl transpeptidase (GGT
      deficient mice) to study the role of glutathione (GSH) in protection against
      oxygen-induced lung injury. These mice had reduced levels of lung GSH and
      restricted ability to synthesize GSH because of low levels of cysteine. When GGT
      deficient mice were exposed to 80% oxygen, they developed diffuse pulmonary
      injury and died within eight days. Ten of 12 wild-type mice were alive after 18
      days. Administration of N-acetylcysteine (NAC) to GGT-deficient mice corrected
      GSH values and prevented the development of severe pulmonary injury and death.
      Oxygen exposure induced an increase in lung GSH levels in both wild-type and GGT
      deficient mice, but induced levels in the mutant mice were <50% of those in wild
      type mice. Cysteine levels were approximately 50-fold lower than GSH levels the
      lungs of both wild-type and GGT-deficient mice. Levels of lung RNA coding for the
      heavy subunit of g-glutamyl cysteine synthetase rose three- to fourfold after
      oxygen exposure in both wild-type and GGT-deficient mice. In contrast, oxygen
      exposure failed to provoke increases in glutathione synthetase, glutathione
      peroxidase, glutaredoxin, or thioredoxin.

PMID- 11976902
TI  - Application of real-time confocal microscopy to intracellular calcium ion
      dynamics in rat arterioles.
AB  - The regulation of cytosolic Ca(2+) homeostasis is essential for cells, including
      vascular smooth muscle cells. Arterial tone, which underlies the maintenance of
      peripheral resistance in the circulation, is a major contributor to the control
      of blood pressure. Confocal microscopy was employed to study the alteration in
      intracellular calcium ion concentration ([Ca(2+)](i)) in arterioles (external
      diameters <100 microm) with respect to selected modifying reagents. 5
      Hydroxytryptamine (1 microM), ATP (10 microM), and endothelin 1-3 (5 nM) elicited
      an increase in [Ca(2+)](i) in most arteriole smooth muscle cells. The [Ca(2+)](i)
      increase sometimes propagated in an intercellular manner. When noradrenaline (10
      microM) was used as a stimulant, [Ca(2+)](i) increase was observed only in a
      portion of the smooth muscle cells. It was also noted that the reaction of these
      cells with respect to ATP is different between testis and brain arterioles; the
      [Ca(2+)](i) increase in testicular arterioles is dependent on Ca(2+) influx from
      extracellular space, whereas in cerebral arterioles it plays a role in both the
      influx of extracellular Ca(2+) and the release of Ca(2+) from intracellular
      stores (i.e., sarco/endoplasmic reticulum). These results indicate that
      arterioles in different tissues may differ greatly in their responses. Real-time
      confocal microscopy was found to be a useful tool for investigating the
      structural and functional changes in living tissues.

PMID- 11976904
TI  - A monoclonal antibody against a neuron-specific 65-kDa protein with laminar
      expression in the developing cerebral cortex.
AB  - The extracellular matrix component chondroitin sulfate supports the survival of
      neocortical neurons and influences their differentiation in culture. During
      development of the rat forebrain expression of chondroitin sulfate peaks at
      around birth. To elucidate functional partners of this important player of
      neurogenesis, a monoclonal antibody, termed MAb-9, was generated after
      immunization with chondroitin sulfate-binding proteins from neonatal rat brain.
      In western blots of neonatal tissue, MAb-9 recognized a major brain-specific 65
      kDa protein band. While most of the 65-kDa protein was present in the soluble
      compartment, a significant fraction was membrane-associated. Prolonged extraction
      of brain membranes with CHAPS revealed three additional minor protein bands of
      approximately 48, 50, and 58 kDa. Of these, the 50-kDa protein specifically bound
      to chondroitin sulfate C-Sepharose. Immunocytochemical studies and western blot
      analyses of cultures of neocortical neurons and astrocytes demonstrated that MAb
      9 recognizes a neuron-specific cytosolic protein. In the developing cerebral
      cortex the protein was detectable by immunohistochemistry in the preplate and
      ventricular zones as early as embryonic day 15. On embryonic day 18, the protein
      was found in the marginal zone and the subplate, but it was not present in the
      emerging cortical plate. At the neonatal stage the immunoreactivity was
      distributed throughout the cerebral cortex with prominent staining of the
      marginal zone. A similar pattern was observed in the adult animal. Notably, the
      laminar distribution of MAb-9 immunoreactivity in the cerebral cortex during the
      prenatal period closely resembled the expression pattern reported for chondroitin
      sulfate. Thus, MAb-9 recognizes a neuronal cytosolic protein which might
      participate in neurotrophic signaling events triggered by chondroitin sulfate.

PMID- 11976903
TI  - A ZO1-GFP fusion protein to study the dynamics of tight junctions in living
      cells.
AB  - To examine the dynamics of tight junctions (TJs) in living cells, chimera between
      the TJ-associated protein ZO-1 and green fluorescent protein (GFP) were
      constructed. If ZO-1 fused to the C-terminus of GFP (ZO1-CGFP) was stably
      expressed in MDCK cells, it was fully incorporated into TJs and colocalized with
      endogenous ZO-1. The GFP tag did not influence cell growth, transepithelial
      electrical resistance, and paracellular mannitol transport. The morphology of the
      transfected cells was unchanged. The ZO1-CGFP MDCK cell line thus represents an
      excellent tool to study TJ dynamics. The influence of the external calcium ion
      concentration on the formation and dynamics of TJs in living cells was thus
      explored. Upon opening of the TJs under short-term treatment with EGTA (up to 20
      min), the localization of ZO1-CGFP at the membrane persisted. The rim-like
      pattern around the individual cells appeared fuzzier than in non-treated cells.
      Long-term calcium depletion resulted in the localization of ZO1-CGFP in the
      cytoplasm and the nucleus. After restoration of normal Ca(2+) concentrations,
      cell-cell contacts were restored and the localization of ZO1-CGFP was
      indistinguishable from the one in control cells kept at normal Ca(2+)
      concentrations. It remains open how the different localizations of ZO-1
      correspond to changes in the signal transduction activity of the molecule.

PMID- 11976905
TI  - Visualisation of hyaluronan and hyaluronan-binding proteins within ovine
      vertebral cartilages using biotinylated aggrecan G1-link complex and biotinylated
      hyaluronan oligosaccharides.
AB  - The aim of this study was to localise hyaluronan (HA)-binding proteins (HABPs) in
      ovine vertebral tissues using biotinylated HA oligosaccharides (bHA oligos) as
      novel affinity probes and to compare this with the distribution of tissue HA
      visualised using biotinylated aggrecan G1 domain-link protein complex. The bHA
      oligos, with a size of 6-18 disaccharides were prepared by partial digestion of
      HA with ovine testicular hyaluronidase, labelled with biotin hydrazide and
      purified by a combination of aggrecan G1 domain and avidin affinity
      chromatography. Hyaluronan and HABPs were both prominent pericellular components
      of hypertrophic cells of the vertebral epiphyseal growth plate and enlarged cells
      in the cartilaginous end plate of the disc. The bHA oligo probe also visualised
      HABPs intracellularly in hypertrophic cells, which also contained intracellular
      HA. Monolayer cultures of ovine annulus fibrosus and nucleus pulposus cells
      rapidly internalised the bHA oligo affinity probe which was subsequently
      visualised by indirect fluorescence using avidin-FITC, to cytoplasm and discrete
      nuclear regions. The results indicate that the abundant pericellular and
      intracellular HA associated with cartilaginous cells in the vertebral tissues is
      colocalised with HABPs. The bHA oligo affinity probe may have further
      applications in investigations of intracellular HABPs, HA endocytosis and the
      roles they play in cellular regulatory processes.

PMID- 11976906
TI  - Immunolocalization of potassium-chloride cotransporter polypeptides in rat
      exocrine glands.
AB  - Potassium-chloride cotransporters (KCCs) encoded by at least four homologous
      genes are believed to contribute to cell volume regulation and transepithelial
      ion transport. We have studied KCC polypeptide expression and immunolocalization
      of KCCs in rat salivary glands and pancreas. Immunoblot analysis of
      submandibular, parotid, and pancreas plasma membrane fractions with
      immunospecific antibodies raised against mouse KCC1 revealed protein bands at ca
      135 kDa and ca 150 kDa. Immunocytochemical analysis of fixed salivary and
      pancreas tissue revealed basolateral KCC1 distribution in rat parotid and
      pancreatic acinar cells, as well as in parotid, submandibular, and pancreatic
      duct cells. KCC1 or the polypeptide product(s) of one or more additional KCC
      genes was also expressed in the basolateral membranes of submandibular acinar
      cells. Both immunoblot and immunofluorescence signals were abolished in the
      presence of the peptide antigen. These results establish the presence in rat
      exocrine glands of KCC1 and likely other KCC polypeptides, and suggest a
      contribution of KCC polypeptides to transepithelial Cl(-) transport.

PMID- 11976907
TI  - GalNAc moieties in O-linked oligosaccharides of the primordial germ cells of
      Xenopus embryos.
AB  - Glycoconjugates could play a role in cell adhesion and migration mechanisms,
      including the locomotive movements of the primordial germ cells (PGCs) during the
      development of the embryo. In the present work, we have studied by lectin
      histochemistry the presence of N-acetylgalactosamine (GalNAc) in the glycans of
      the Xenopus PGCs, as a first approach to identifying their glycoconjugates which
      could be involved in the migration mechanism. The PGCs were negative for three of
      the GalNAc-binding lectins employed (from soybean, SBA; from lima bean, LBA; and
      from snail, HPA). However, when sialic acid (NeuAc) was previously removed by
      acid hydrolysis, SBA and HPA, but not LBA, labeled the PGCs, except if the
      staining was combined with the beta-elimination procedure. This suggests the
      presence of GalNAc alpha(1,3)-linked to galactose (Gal) in O-linked
      oligosaccharides, in a subterminal position to NeuAc. As the PGCs were always
      negative for LBA, the absence of fucose alpha(1,2)-linked to subterminal Gal is
      suggested. With the lectin from horse gram (DBA), the PGCs were stained, although
      beta-elimination turned the cells negative and acid hydrolysis increased the
      labeling, suggesting that GalNAc(alpha)(1,3)GalNAc was in O-linked glycans in
      terminal and subterminal to NeuAc position.

PMID- 11976908
TI  - Analysis of maturation states of rat bone marrow-derived dendritic cells using an
      improved culture technique.
AB  - In this study, we examined in more detail the development of rat bone marrow
      derived dendritic cells (BMDC). A two-stage culture system was used to propagate
      BMDC from rat bone marrow precursors. BMDC developed within clusters of
      proliferating cells after repetitive addition of rat granulocyte/macrophage
      colony-stimulating factor and rat interleukin (IL)-4 at a concentration of 5
      ng/ml to the cultures. Fluorescence-activated cell sorter analysis performed at
      an early stage of development (day 6) revealed an immature phenotype with
      intermediate levels of major histocompatibility complex (MHC) class II expression
      and low levels of the costimulator molecules CD80 and CD86. Upon further culture,
      a strong upregulation of MHC class II, costimulatory and adhesion molecules could
      be observed, whereas macrophage marker antigens were downregulated. Late-stage
      BMDC (day 10) showed a high expression of MHC class I and II, ICAM-1, Ox62 and
      CD11c, and revealed a split pattern of B7-1 and B7-2. The cell yield was about
      40% of the initially plated bone marrow cells with 80% MHC class II-high and less
      than 20% MHC class II-low positive cells. Full maturation of rat BMDC (day 12)
      with an almost uniform expression of B7 was achieved by subsequent subculture and
      further stimulation with rat tumour necrosis factor alpha (TNF-alpha),
      lipopolysaccharide (LPS) or soluble CD40 ligand (CD40L). Analysis of the cell
      supernatant revealed a strong IL-12 production after LPS or CD40L, and to a
      lesser extent after TNF-alpha stimulation. Additionally, LPS-treated, but not
      CD40L-treated BMDC secreted TNF-alpha into the supernatant. Early-stage BMDC
      sufficiently triggered a T cell receptor (TCR) downregulation, but did not
      stimulate naive T cells in an allogeneic mixed leukocyte reaction (MLR) and
      revealed a low stimulatory capacity in an antigen-specific T cell assay. In
      contrast, late-stage BMDC and especially fully mature BMDC strongly induced TCR
      internalisation, elicited high T cell responses in the allogeneic MLR similar to
      those obtained by mature rat spleen dendritic cells and efficiently activated
      antigen-specific T cells. In conclusion, this protocol allows easy access to
      large numbers of rat BMDC at defined maturation stages and selective studies for
      the manipulation of immune responses in rat models.

PMID- 11976909
TI  - Vimentin-positive cells in the villus epithelium of the rabbit small intestine.
AB  - In rabbit intestinal epithelium, vimentin intermediate filaments are selectively
      expressed in the M cells of follicle-associated epithelium (FAE). To find
      intestinal epithelial cells belonging to the M cell lineage, vimentin was
      detected immunohistochemically in the rabbit small and large intestines. Vimentin
      positive columnar cells were scattered throughout the villus epithelium of the
      small intestine. In their cytoplasm, vimentin was located from the perinuclear
      region to the cell membrane touching intraepithelial lymphocytes. These cells had
      microvilli shorter than those of absorptive cells, and the alkaline phosphatase
      activity of the microvilli was markedly weaker than that of absorptive cell
      microvilli. Glycoconjugates on the surface of the microvilli were alcian blue
      positive and periodic acid-Schiff negative. The morphological and histochemical
      features of these vimentin-positive villus epithelial cells differed from those
      of adjacent absorptive cells and closely resembled those of the M cells in FAE
      covering Peyer's patches and solitary lymphatic nodules. These results suggest
      that the vimentin-positive cells in the villus epithelium belong to the M cell
      lineage.

PMID- 11976910
TI  - Nestin expression in rat adrenal gland.
AB  - The constituents of the intermediate filament network of adrenal gland cells have
      not been deeply investigated in vivo. Adrenocortical cells have been reported to
      express cytokeratins and vimentin, but the intermediate filament components of
      the adrenomedullary cells are still unknown. Nestin is an intermediate filament
      protein that is mainly expressed in the developing nervous and muscle systems. It
      has been reported to be unable to form filaments by itself and it co-assembles
      with vimentin. Using immunocytochemical and biochemical approaches, the present
      study demonstrates that nestin is expressed in situ either in the cortex or in
      the medulla of adult rat adrenal glands. Nestin-negative cells prevalently form
      the zona glomerulosa whereas the zona fasciculata and the zona reticularis are
      mainly nestin-immunoreactive. Nestin-positive cells always express vimentin-like
      immunoreactivity but several cells apparently expressing only vimentin are
      detectable too. Nestin is also expressed by adrenomedullary cells that also
      display a faint vimentin-like immunoreactivity. We hypothesise that the
      inconstant detection of nestin in adrenocortical cells depends on their different
      functional moments. Moreover, even though our data do not allow to confirm
      vimentin in adrenomedullary cells, in situ detection of nestin in the adrenal
      medulla indirectly supports in vivo expression of vimentin in chromaffin cells.

PMID- 11976912
TI  - Molecular and functional aspects of anionic channels activated during regulatory
      volume decrease in mammalian cells.
AB  - The ability of cells to readjust their volume after swelling, a phenomenon known
      as regulatory volume decrease (RVD), is a fundamental biological achievement
      guaranteeing survival and function of cells under osmotic stress. This article
      reviews the mechanisms of RVD in mammalian cells with special emphasis on the
      activation of ion channels during RVD.

PMID- 11976913
TI  - Glutamate-receptor-induced modulation of GABAergic synaptic transmission in the
      hippocampus.
AB  - There is a large body of evidence about the short- and long-term changes in
      GABAergic transmission in the hippocampus produced by the action of different
      endogenous neuromodulators and in particular neurotransmitters. Both intrinsic
      hippocampal cells and afferent fibres coming into the hippocampus from various
      parts of the CNS release substances that are capable of changing inhibitory
      transmission. This review surveys current understanding of the action of
      glutamate on the inhibitory transmission mediated in the hippocampus via GABA(A)
      receptors. Here we pay special attention to the molecular and cellular mechanisms
      leading to spatio-temporal changes of the glutamate concentration in the
      extracellular space and to the localization and identity of glutamate receptors
      involved in this direct modulation of inhibition.

PMID- 11976914
TI  - Radial mass transfer of cross-bridges in a tetanized ferret heart muscle.
AB  - An X-ray diffraction experiment on ferret heart muscle was made to examine the
      relationship between tension and mass transfer from the thick to the thin
      filament associated with the interaction of cross-bridges with actin. A ferret
      papillary muscle was electrically stimulated for 8 s in the presence of 5 microM
      ryanodine to give a tetanus. At different extracellular Ca2+ concentrations (2-20
      mM), a linear relationship was found between the tension and the mass transfer.
      It was concluded that a change in tension caused by altering the extracellular
      Ca2+ concentration is due to a change in the number of myosin heads bound to
      actin. This is in contrast to the results obtained on skinned preparations, which
      showed a markedly nonlinear relationship between the number of heads in the
      vicinity of the thin filaments and force. It was found that the tension per
      myosin head is similar in twitch and tetanus of cardiac muscle. Also, a similar
      fraction of myosin heads is recruited in tetanus of cardiac and skeletal muscles.

PMID- 11976915
TI  - Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic
      B-cells.
AB  - A readily releasable pool (RRP) of granules has been proposed to underlie the
      first phase of insulin secretion. In the present study we combined electron
      microscopy, insulin secretion measurements and recordings of cell capacitance in
      an attempt to define this pool ultrastructurally. Mouse pancreatic B-cells
      contain approximately 9,000 granules, of which 7% are docked below the plasma
      membrane. The number of docked granules was reduced by 30% (200 granules) during
      10 min stimulation with high K+. This stimulus depolarized the cell to -10 mV,
      elevated cytosolic [Ca2+] ([Ca2+](i)) from a basal concentration of 130 nM to a
      peak of 1.3 microM and released 0.5 ng insulin/islet, corresponding to 200-300
      granules/cell. The Ca2+ transient decayed towards the prestimulatory
      concentration within approximately 200 s, presumably reflecting Ca2+ channel
      inactivation. Renewed stimulation with high K+ failed to stimulate insulin
      secretion when applied in the absence of glucose. The size of the RRP, derived
      from the insulin measurements, is similar to that estimated from the increase in
      cell capacitance elicited by photolytic release of caged Ca2+. We propose that
      the RRP represents a subset of the docked pool of granules and that replenishment
      of RRP can be accounted for largely by chemical modification of granules already
      in place or situated close to the plasma membrane.

PMID- 11976916
TI  - Calsequestrin expression and calcium binding is increased in streptozotocin
      induced diabetic rat skeletal muscle though not in cardiac muscle.
AB  - Altered mechanisms of Ca2+ transport may underlie the contractile dysfunctions
      that have been frequently reported to occur in diabetic cardiac and skeletal
      muscle tissues. Calsequestrin, a high-capacity Ca2+-binding protein, is involved
      in the regulation of the excitation-contraction-relaxation cycle of both skeletal
      and cardiac muscle fibres. We have investigated the expression of calsequestrin
      and Ca2+ binding in cardiac and skeletal muscle from streptozotocin-induced
      diabetic rat. Immunoblotting of microsomal membranes from normal and
      streptozotocin-induced diabetic muscle revealed no significant changes in heart,
      but an increase in the relative abundance of calsequestrin and calsequestrin-like
      proteins in skeletal muscle. In analogy, the overall Ca2+-binding capacity of
      sarcoplasmic reticulum vesicles from diabetic skeletal muscle was drastically
      increased. The expression of fast muscle marker proteins was not affected,
      indicating that no relevant fibre transformation occurred in streptozotocin
      treated rat muscles. The up-regulation of the high-capacity Ca2+-binding element
      calsequestrin might represent a compensatory mechanism of diabetic skeletal
      muscle. An increased Ca2+-buffering capacity of the sarcoplasmic reticulum lumen
      might counteract elevated cytosolic Ca2+ levels in diabetes thereby preventing
      Ca2+-dependent myo-necrosis.

PMID- 11976918
TI  - Effect of a short photoperiod on circadian rhythms of body temperature and motor
      activity in old rats.
AB  - Circadian rhythms of body temperature and motor activity were documented in young
      and old rats (four 8-week-old and five 22-month-old male Wistars, implanted with
      telemetric probes and housed in a chronobiological facility) under two different
      photoperiod conditions. The animals were maintained in a light:dark (LD) cycle of
      12 h each (LD 12:12) for 4 weeks and then exposed to a LD 6:18 cycle for 7 weeks
      to assess the effect of age on the desynchronization of the temporal structure of
      the rhythms. In old rats under LD 12:12, the power of the 24-h component and the
      circadian amplitude of body temperature and motor activity were markedly lower
      than in the young and both rhythms were phase-advanced. After the shift to LD
      6:18, the circadian rhythmicity was maintained for both variables and the same
      phase delay (+5+/-1 h) was observed in both age groups, as was a gradual
      expansion of the patterns of both functions with the longer night. The
      photoperiod reduction (6 weeks under LD 6:18) did not modify the power of the 24
      h component of body temperature and motor activity in old rats. In young rats,
      however, the power and amplitude of the 24-h component of motor activity rhythm
      fell to the levels of those in old rats, while the power of the 24-h component of
      body temperature rhythm and the amplitude did not change. Our data show that the
      circadian rhythm of motor activity, but not of body temperature, responds age
      dependently to a photoperiod reduction.

PMID- 11976917
TI  - Short-term effects of forced eccentric contractions on collagen synthesis and
      degradation in rat skeletal muscle.
AB  - Acute downhill running has been shown to activate matrix metalloproteinase- (MMP
      ) 2 and to change type IV collagen concentration in some muscle types. In order
      to study the influence of more intense exercise on total collagen and type IV
      collagen concentrations, molecules regulating their synthesis and degradation
      were investigated after forced lengthening contractions in rat skeletal muscle.
      Tibialis anterior (TA) muscle of 24 male Wistar rats was subjected to 240 forced
      lengthening contractions. TA muscle was excised at consecutive time points (0 and
      6 h, 2, 4, and 7 days) after stimulation. With immunohistochemistry, types I, III
      and IV collagen were located in the swollen, necrotic and regenerated fibres in a
      similar manner as in intact undamaged skeletal muscle fibre. An increase in the
      activity of prolyl 4-hydroxylase was indicative of an overall elevated collagen
      biosynthesis. No change was demonstrated in total collagen concentration, whereas
      type IV collagen concentration increased after exercise. MMP-2 and MMP-9, which
      are the proteins that degrade type IV collagen, elevated after exercise. In
      conclusion, the increase in type IV collagen concentration seems to be the result
      of an increase in both the synthesis and activation of degrading enzymes and
      their inhibitors during recovery after forced lengthening contractions.

PMID- 11976919
TI  - Functional interaction between KChIP1 and GFP-fused Kv4.3L co-expressed in HEK293
      cells.
AB  - The trafficking and electrophysiological characteristics of Kv4 subfamily are
      regulated by K+-channel-interacting proteins (KChIPs), which bind to the N
      terminus of Kv4. We examined in HEK293 expression system whether the fusion of a
      green fluorescence protein (GFP) with Kv4.3L at the N-terminus would affect the
      functional interaction of KChIP1 with Kv4.3L. GFP-fused Kv4.3L showed A-type K+
      current (I(A)) with significantly slower recovery from inactivation (tau=218 and
      496 ms) and much lower density than those of original Kv4.3L expressed in HEK293
      cells. The co-expression of KChIP1 with Kv4.3L strikingly increased the density
      of I(A) and hastened the recovery from inactivation (tau=133 ms). Surprisingly,
      co-expression of KChIP1 with GFP-fused Kv4.3L markedly enhanced the current
      density and hastened the recovery (tau=135 ms), just as the co-expression of
      KChIP1 with Kv4.3L did. In conclusion, the fusion of GFP to the N-terminus of
      Kv4.3L per se changed the channel kinetics but did not affect the functional
      interaction of KChIP1 with Kv4.3L at all. The trafficking of Kv4.3L by KChIP1 to
      the cell membrane was visualized with GFP fusion to the N-terminus without any
      significant modification of changes in channel kinetics and density.

PMID- 11976920
TI  - beta-Adrenergic modulation of prepulse facilitation of L-type calcium channels in
      rabbit ventricular myocytes.
AB  - It is reported that strong depolarization augments cardiac L-type Ca currents by
      inducing the special gating mode with long-lasting openings (mode 2) (Pietrobon
      and Hess Nature 346:651-655, 1990). However, a prepulse to +90 mV did not
      obviously facilitate the current at 0 mV in rabbit ventricular myocytes as
      measured in the whole-cell configuration of the patch-clamp method in the
      presence of 2 mM BaCl(2) in the external solution. In the presence of
      isoproterenol (1 microM), the inactivation during the prepulse was attenuated,
      and the prepulse evoked facilitation. However, the current at 0 mV whose
      amplitude was normalized to the extent of the inactivation at +90 mV still
      exhibited greater facilitation in the presence than in the absence of
      isoproterenol. In the cell-attached configuration with 110 mM BaCl(2) in
      pipettes, repolarization from +110 to +20 mV yielded mainly blank sweeps (mode 0)
      and only occasionally mode 2, leading to no facilitation of the average current.
      Isoproterenol augmented the prepulse-induced increase in mode 2, reciprocally
      inhibited that in mode 0, and increased the fraction of mode 2 in non-blank
      sweeps after the prepulse. Therefore, beta-adrenergic stimulation favors mode 2
      rather than mode 0 at strongly depolarized potentials, thereby promoting the
      prepulse facilitation and attenuating the inactivation of cardiac L-type Ca
      currents.

PMID- 11976921
TI  - Voltage-dependent changes in specific membrane capacitance caused by prestin, the
      outer hair cell lateral membrane motor.
AB  - In the outer hair cell (OHC), membrane capacitance principally derives from two
      components - that associated with lateral membrane sensor/motor charge movement,
      and that proportional to the membrane surface area (C(sa)). We used measures of
      membrane capacitance to test a model hypothesis that OHC lateral membrane
      molecular motors, recently identified as the protein prestin, fluctuate between
      two area states. By measuring membrane capacitance in native OHCs or prestin
      transfected HEK cells at extreme voltages (+/-200 mV) where motor-derived charge
      movement is small or absent, we observed that C(sa) depends on the state of the
      motors, or correspondingly on membrane voltage. Deiters cells or control HEK
      cells, which lack motors, do not show this dependence. We modeled the voltage
      dependent change in C(sa) as a Boltzmann process with the same parameters that
      describe the charge movement of the motors' voltage sensors. C(sa) is 3.28+/-0.75
      pF (mean +/-SD; n=23) larger during extreme hyperpolarization, and the number of
      motors in OHCs and prestin-transfected HEK cells correlates with the magnitude of
      Delta C(sa)( r=0.78). Although these data are consistent with the area motor
      model, the corresponding area change, assuming 0.5 microF/cm(2) under constant
      membrane thickness, is unphysiologically large, and indicates that the
      capacitance change must result from changes not only in lateral membrane area but
      also specific capacitance. Thus, we conclude that a conformational change in the
      lateral membrane motor, prestin, additionally alters the dielectric constant
      and/or thickness of the lateral plasma membrane.

PMID- 11976922
TI  - Angiotensin II increases L-type Ca2+ current in gramicidin D-perforated adult
      rabbit ventricular myocytes: comparison with conventional patch-clamp method.
AB  - The effects of angiotensin II (Ang II) on L-type Ca2+ current (I(Ca,L)) remains
      controversial. We studied the effects of Ang II on I(Ca,L) in single adult rabbit
      ventricular myocytes using a perforated patch-clamp technique with gramicidin D.
      Ang II increased I(Ca,L) in a concentration-dependent manner (EC(50)=0.75 nM). In
      contrast, in conventional whole-cell patch-calmp, I(Ca,L)ran down gradually and
      the I(Ca,L) response to Ang II was variable, suggesting the potential loss of
      diffusible components crucial for the Ang II-induced signaling process. An AT(1)
      antagonist, CV11974 (0.1 microM), completely inhibited the increase in I(Ca,L)
      induced by Ang II (0.1 microM), whereas an AT(2) antagonist, PD123319 (10
      microM), did not influence the I(Ca,L) increase. Neither pre- nor after-treatment
      with a Na+/H+ exchange (NHE) inhibitor HOE642 (1 microM) affected the Ang II
      induced increase in I(Ca,L). The protein kinase C (PKC) inhibitor chelerythrine
      (1 microM) did not affect the Ang II-induced I(Ca,L) increase. The present
      findings indicate that Ang II increases I(Ca,L) via AT(1) receptors in adult
      rabbit ventricular myocytes. Neither the activation of NHE nor PKC may contribute
      to the Ang II-induced activation of I(Ca,L).

PMID- 11976923
TI  - Interactions of temperature and angiotensin II in paraventricular neurons of rats
      in vitro.
AB  - We recorded extracellular impulse activity of hypothalamic paraventricular
      neurons ( n=75) in rat brain slices during application of angiotensin II (ANG II,
      10(-9)-10(-6) M) and/or temperature changes (32-42 degrees C). ANG II, with a
      threshold concentration of 10(-8) M, increased the firing rate in more than 80%
      of the neurons with strongest excitations occurring in bursting neurons.
      Increasing the temperature also raised the discharge rate in the majority of the
      neurons, often together with enhanced burst discharges. When ANG II was applied
      during ongoing sinusoidal temperature changes, its effects were more pronounced
      at elevated temperatures. These electrophysiological data illustrate that
      stimulus-encoding properties at the neuronal level can contribute to the
      interactions between osmoregulatory and thermoregulatory mechanisms including
      mutual sensitization when different stimuli (here: ANG II and temperature
      changes) are applied simultaneously.

PMID- 11976924
TI  - Attenuated "cross talk" between kappa-opioid receptors and beta-adrenoceptors in
      the heart of chronically hypoxic rats.
AB  - At 0.1-1 microM, U50488H, a kappa-opioid receptor agonist, inhibited the
      stimulatory effects of 1 microM isoprenaline, a beta-adrenoceptor agonist, on the
      electrically induced intracellular Ca2+ ([Ca2+](i)) transient and cAMP
      accumulation ("cross talk" between kappa-opioid receptors and beta-adrenoceptors)
      in the presence of 1 microM ICI118,551, a beta(2)-adrenoceptor antagonist in
      ventricular myocytes from both normoxic and chronically hypoxic rats.
      Pretreatment with 20 microg/ml cholera toxin increased the ADP-ribosylation of
      Gsalpha subunits and the electrically induced [Ca2+](i) transient in both
      normoxic and chronically hypoxic rats. The effects of cholera toxin were
      inhibited by 1 microM U50488H and the inhibitory effect of U50488H was attenuated
      in chronically hypoxic rats. Similarly, 1 microM forskolin also increased the
      electrically induced [Ca2+](i) transient and cAMP accumulation, which were both
      inhibited by U50488H, in both normoxic and chronically hypoxic rats. The
      inhibitory effects of 1 microM U50488H were significantly attenuated in
      chronically hypoxic rats. The results are novel findings, in that the "cross
      talk" between kappa-opioid receptors and beta-adrenoceptors is attenuated
      following chronic hypoxia. The attenuation may be due to decreased responses of
      Gs-protein and adenylyl cyclase to kappa-opioid receptor activation in addition
      to desensitization of the receptor itself.

PMID- 11976925
TI  - Acetylcholine and potassium elicit different patterns of exocytosis in chromaffin
      cells when the intracellular calcium handling is disturbed.
AB  - During fast superfusion of bovine chromaffin cells with normal Krebs-HEPES
      solution containing 2 mM Ca2+, pulses of 100 microM ACh or 100 mM K+ of
      increasing duration (1-5 s) caused similar exocytosis of about 3-4 microC
      catecholamine. Depletion of endoplasmic reticulum (ER) Ca2+ by pretreatment with
      1 microM thapsigargin, 10 mM caffeine and 10 microM ryanodine more than halved
      the responses to ACh but did not affect the responses to K+ responses. In these
      ER Ca2+-depleted cells the protonophore carbonylcyanide p
      (trifluoromethoxy)phenylhydrazone (FCCP) (20 microM given during the 5 s
      preceding each pulse) augmented the responses to ACh responses fourfold for all
      pulse durations applied (1-5 s) whereas responses to K+ were potentiated twofold
      with 1 to 2 s pulses but were not affected with longer pulse durations. ACh
      pulses applied to fura-2-loaded cells evoked increases of bulk cytosolic [Ca2+]
      ([Ca2+](c)) that were substantially smaller than those elicited by K+ pulses.
      Confocal microscopy of fluo-3-loaded cells showed that ACh pulses elicited
      discrete and more localized [Ca2+](c) elevations, whereas K+ pulses produced
      higher [Ca2+](c) transients that spread out quickly throughout the cytosol. These
      results suggest that mitochondria sense the increase of local [Ca2+](c) elicited
      by ACh (that evokes firing of action potentials) much better than that induced by
      K+ (that produces sustained cell depolarisation). This implies that mitochondria
      are more sensitive to the local [Ca2+](c) changes resulting from the
      physiological triggering of action potentials by ACh.

PMID- 11976927
TI  - Cell membrane destabilizes progressively during repetitive mechanical rupture
      events.
AB  - The postfusion oscillation cycle method of electrofused cells was applied to red
      blood cell membranes to induce repetitive membrane ruptures and test the
      mechanical membrane resistance against sequential events of membrane strain and
      rupture. After producing doublets from pairs of electrofused cells, they entered
      the oscillation cycle, providing a sequence of at least four consecutive
      colloidosmotic-driven rupture events. Different gradations of colloidosmotic
      pressure loads between 3230 Pa and 8640 Pa were established with various buffer
      types. The independence of buffer type and geometrical and mechanical
      observations has been verified independently for both parts of the oscillation
      sequence. With decreasing colloidosmotic inducement, caused by repetitive
      oscillation cycles, an increasing susceptibility of the cell membrane against
      membrane rupture was measurable. Since side-effects had been eliminated, it could
      be concluded that the cell membrane resistance against repetitive mechanical
      ruptures decreases.

PMID- 11976926
TI  - Dehydration modifies guanidino compound concentrations in the different zones of
      the rat kidney.
AB  - Guanidino compounds (GCs) related to arginine (Arg) are unevenly distributed
      along the cortico-papillary axis of the rat kidney. Inasmuch as the concentration
      of alpha-keto-delta-guanidinovaleric acid (alpha-keto-delta-GVA),
      guanidinosuccinic acid (GSA), creatinine (CTN), gamma-guanidinobutyric acid
      (gamma-GBA) and methylguanidine (MG) increased steeply along the inner medulla in
      parallel to the urea and osmotic gradients, the question arose as to whether
      dehydration enhances their renal content and distribution. To examine this
      possibility, adult male rats were dehydrated by removing the drinking water for
      24 or 48 h. The kidneys were sliced and cut in seven sections along the cortico
      papillary axis. Twelve GCs were determined by liquid chromatography in each renal
      zone. Dehydration modified GC concentrations and regional distribution. The renal
      content of Arg, guanidine and MG was decreased while that of alpha-keto-delta
      GVA, gamma-GBA, alpha- N-acetyl-arginine and homoarginine remained unchanged. In
      contrast, GSA, guanidinoacetic acid (GAA), creatine (CT), CTN and beta
      guanidinopropionic acid (beta-GPA) concentrations were enhanced significantly in
      different renal zones after 24 and 48 h dehydration. In addition, the tissue
      level of GCs supplying energy, such as CT and beta-GPA, the precursor of CT (GAA)
      and its metabolite (CTN) were enhanced under dehydration. Arg and CT account for
      80-90% of the GCs located in the renal cortex. Variations of some GC levels under
      dehydration may modify enzyme activities, renal metabolism and cell function.

PMID- 11976928
TI  - Regulation of urea permeability in frog urinary bladder by prostaglandin E(2).
AB  - The present study was performed to investigate the role of prostaglandin E(2)
      (PGE(2)) in the regulation of urea transport in the frog urinary bladder, which
      is known to occur via a specialized arginine-vasotocin- (AVT-) regulated urea
      transporter. The bladders isolated from Rana temporaria L. were filled with
      amphibian Ringer solution containing 370 Bq/ml (0.01 microCi/ml) of [14C]urea,
      and urea permeability ( P(urea)) was determined by sampling the serosal and
      mucosal bathing medium at 30-min intervals for measurement of radioactivity. It
      was found that, from the serosal side, PGE(2) (10 nM to 1 microM) caused a dose
      dependent increase in P(urea) [(7.2+/-1.8)x10(-6) cm/s in the presence of 0.5
      microM PGE(2)versus (1.0+/-0.2)x10(-6) cm/s in control, n=9, P<0.001]. As in
      response to AVT, the PGE(2)-induced P(urea)reached a maximum in 1-1.5 h after the
      agonist was added. The stimulatory effects of PGE(2) and AVT applied together
      were not additive. PGE(2)-induced urea transport was strongly inhibited by nearly
      75% in the presence of mucosal or serosal phloretin (10(-4) M). P(urea) was
      enhanced up to (4.7+/-0.8)x10(-6) cm/s (n=12, P<0.001) by butaprost (5 x 10(-6)
      M), a selective EP(2) receptor agonist, while sulprostone (EP(1)/EP(3) agonist,
      10(-6) M) caused no changes in P(urea). PGE(2)dose-dependently increased the
      content of cAMP in mucosal epithelial cells (control: 18.0+/-1.8; 10(-6) M
      PGE(2): 74.2+/-9.3 pmol cAMP/mg protein per 30 min, n=7, P<0.001). Phorbol esters
      did not alter PGE(2)-induced P(urea), whereas H-89 (20 microM), a protein kinase
      A inhibitor, reduced it by 45.1+/-9.9% ( n=5, P<0.05). PGE(2)did not change the
      AVT-stimulated P(urea) measured in isoosmotic conditions, but inhibited the last
      one in the presence of a serosa-to-mucosa osmotic gradient. The data obtained
      show that, in the frog urinary bladder, PGE(2)is a stimulator of phloretin
      inhibitable urea transport. Its effect seems to be mediated by EP(2) receptor
      coupled generation of intracellular cAMP.

PMID- 11976929
TI  - Regulation of cloned, Ca2+-activated K+ channels by cell volume changes.
AB  - Ca2+-activated K+ channels of big (hBK), intermediate (hIK) or small (rSK3)
      conductance were co-expressed with aquaporin 1 (AQP1) in Xenopus laevis oocytes.
      hBK channels were activated by depolarization, whereas hIK and rSK3 channels were
      activated by direct injection of Ca2+ or Cd2+ into the oocyte cytoplasm, before
      the oocytes were subjected to hyperosmolar or hypoosmolar (+/-50 mOsm mannitol)
      challenges. In all cases, the oocytes responded rapidly to the osmotic changes
      with shrinkage or swelling and the effects on the K+ currents were measured. hIK
      and rSK3 currents were highly sensitive to volume changes and increased
      immediately to 178% (hIK) or 165% (rSK3) of control in response to swelling and
      decreased to 64% (hIK) or 61% (rSK3) of control after shrinkage. These responses
      were dependent on the channels being pre-activated and were almost totally
      abolished after injection of cytochalasin D into the oocyte cytoplasm (final
      concentration: 1 microM). In contrast, hBK channels showed only a minor
      sensitivity to volume changes; the hBK channel activity decreased approximately
      20% after swelling and increased approximately 20% after shrinkage. The opposite
      effects of volume changes on hIK/rSK3 and hBK channels suggest that the
      significant stimulation of hIK and rSK3 channels during swelling is not mediated
      by changes in intracellular Ca2+, but rather through interactions with the
      cytoskeleton, provided that a sufficient basal concentration of intracellular
      Ca2+ or Cd2+ is present.

PMID- 11976930
TI  - Augmentation of hypoxia-induced nitric oxide generation in the rat carotid body
      adapted to chronic hypoxia: an involvement of constitutive and inducible nitric
      oxide synthases.
AB  - Acute hypoxia increases the endogenous release of nitric oxide (NO) in rat
      carotid body and the expression of nitric oxide synthases is modulated by chronic
      hypoxia. The aim of the study was to examine hypoxia-induced NO generation in rat
      carotid body adapted to chronic hypoxia with inspired oxygen at 10% for 4 weeks.
      The concentration of NO was measured electrochemically with a Pt/Nafion/Pd
      IrOx/POAP modified electrode inserted into the isolated carotid body superfused
      with bicarbonate-buffer saline at 35 degrees C. Acute hypoxia increased the
      concentration of NO by 471.3+/-71.4 nM in the carotid body of chronically hypoxic
      (CH) rats. The amount of NO release induced by hypoxia was significantly
      augmented when compared with that of the normoxic control (87.6+/-15.9 nM). The
      hypoxia-induced NO generation was markedly attenuated by pretreatment with L- NG
      nitroarginine methylester (L-NAME; 500 microM), a non-selective nitric oxide
      synthase (NOS) inhibitor and also by removal of extracellular calcium with the
      calcium chelator EGTA (5 mM). Additionally, NO generation during hypoxia was
      reduced by 30% in the CH carotid body treated with S-methylisothiourea (SMT; 50
      microM), a specific blocker of inducible NOS (iNOS). Immunohistochemical study
      revealed that positive iNOS protein immunoreactivity was detected in clusters of
      glomus cells in the carotid bodies of CH rats, but not in the normoxic group.
      Thus, chronic hypoxia enhances hypoxia-induced NO generation mediated by calcium
      dependent NOSs and iNOS in the carotid body. Extracellular recording of sinus
      nerve activity of CH carotid bodies showed that L-NAME treatment enhanced the
      afferent discharge in response to hypoxia, confirming that the generation of NO
      suppresses the activities of carotid chemoreceptors. Taken together, our results
      suggest that hypoxia-induced NO production increases in the rat carotid body
      adapted to chronic hypoxia and that constitutive and inducible NOSs are involved
      in the NO generation. The enhancement of NO generation may play a physiological
      role in blunting the hypoxic chemosensitivity during chronic hypoxia.

PMID- 11976931
TI  - Calcium and voltage-dependent alterations of cell volume in neuroblastomaxglioma
      hybrid NG108-15 cells.
AB  - Intracellular calcium ([Ca2+](i)), cell volume, membrane potential and currents
      were measured in neuroblastomaxglioma hybrid cells to gain insight into how
      [Ca2+](i) controls cell volume. [Ca2+](i) was increased by fluid shear stress,
      mechanical stimulation of the cells, the Ca2+ ionophore A23187, caffeine and
      thapsigargin. The increase in [Ca2+](i) induced by mechanical stimulation was
      decreased by about 50% by caffeine and abolished after incubation of the cells in
      a Ca2+-free solution. Mechanical stimulation by stirring the cell suspension
      induced cell shrinkage that was abolished by caffeine, but induced cell swelling
      in Ca2+-free solution. In the presence of caffeine, A23187 induced cell shrinkage
      whereas thapsigargin induced cell swelling. Both cell volume changes were
      inhibited by the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic
      acid. The cells were hyperpolarized by fluid shear stress and A23187 and
      depolarized by caffeine, thapsigargin and intracellular EGTA. Under all these
      conditions, the membrane input resistance was decreased. Voltage-clamp
      experiments suggested that, in addition to an increased anionic current, fluid
      shear stress and A23187 increased a K+ current, whereas caffeine and
      intracellular Ca2+ chelation increased a non-selective cation current and
      thapsigargin increased both a K+ and a non-selective cation current. Taken
      together, these results suggest that, if cell volume is closely dependent on
      [Ca2+](i) and the activity of Cl- channels, its relative value is dependent on
      the ionic selectivity of co-activated channels and the membrane potential.

PMID- 11976932
TI  - Aldosterone and high-NaCl diet modulate ClC-2 chloride channel gene expression in
      rat kidney.
AB  - It is well known that Na+ reabsorption in the kidney can be regulated by
      aldosterone. Although Cl- is the most abundant anion present in the extra
      cellular fluids the involvement of aldosterone in the regulation of Cl-
      conductance through Cl- channels at the molecular level is unknown. In this
      study, the effects of aldosterone and high-Na+ diet on the expression of ClC-2, a
      cell volume-, pH- and voltage-sensitive Cl- channel, was examined in the rat
      kidney. Total RNA isolated from Wistar rats fed a high-Na+ diet for 5 days,
      furosemide treatment, adrenalectomy and adrenalectomy with replacement of normal
      plasma levels of aldosterone were compared by the use of ribonuclease protection
      assay (RPA), and/or a semi-quantitative RT-PCR. The high-Na+ diet reduced renal
      mRNA and protein ClC-2 expression. The renal expression of ClC-2 mRNA decreased
      in adrenalectomized rats and was restored by plasma aldosterone replacement. In
      addition, the semi-quantitative RT-PCR in different segments of the nephron
      showed that these changes were secondary to the modulation of ClC-2 mRNA
      expression by aldosterone in the cortical and medullary segments of thick
      ascending limbs of Henle's loop. These results suggest that ClC-2 may be involved
      with aldosterone-induced Cl- transport in the kidney.

PMID- 11976933
TI  - Gating kinetics and ligand sensitivity modified by phosphorylation of cardiac
      ryanodine receptors.
AB  - The effects of protein-kinase- (PKA-) dependent phosphorylation on the stationary
      gating kinetics of single ryanodine receptor (RyR) channels was defined. The
      single-channel activity from canine cardiac RyR was reconstituted into planar
      lipid bilayers. Exogenously applied PKA increased the single-channel open
      probability ( P(o)) of both native and purified cardiac RyR channels, after
      preincubation with ATP and Mg2+. The action of PKA on the RyR channel occurred
      only in the presence of ATP and adenosine 5'- O-(3-thiotriphosphate) (ATPgammaS),
      but not in the presence of 5'-adenylimidodiphosphate (AMP-PCP). Thus, the action
      of PKA requires the presence of a hydrolyzable ATP analog. PKA-induced channel
      activation was blocked by specific PKA inhibitors. All these results confirmed
      that the RyR channel can be phosphorylated by exogenous protein kinase. The
      gating kinetics of single RyR channels before PKA treatment were significantly
      altered by ATP and Mg2+ as physiological ligands. In contrast, after PKA
      treatment, neither ATP nor Mg2+ significantly alters the gating kinetics of these
      channels. PKA-dependent phosphorylation thus decreases the ATP and Mg2+ apparent
      sensitivity in most of the gating parameters of single RyR channels. The
      phosphorylated RyR channels open and close more frequently, stay open for longer,
      and stay closed for shorter periods. The dwell-time histograms obtained
      demonstrate that the phosphorylated and the dephosphorylated channels have
      strikingly different open and closed kinetics at physiological cytoplasmic
      concentrations of Mg and ATP.

PMID- 11976934
TI  - Quantitative determination of cell surface beta-adrenoceptors in different rat
      skeletal muscles.
AB  - In the present study, the density of cell surface beta-adrenergic receptors was
      determined in different skeletal muscles using the hydrophilic ligand [3H]CGP
      12177. The density of beta-adrenergic receptors was highest in the slow-twitch
      soleus muscle (32.8+/-0.9 fmol mg dw(-1)) and lowest in the fast-twitch
      glycolytic white gastrocnemius (10.4+/-0.5 fmol mg dw(-1)) beta-Adrenoceptor
      density correlated closely with the percentage of type-I fibres (r=0.979;
      P<0.0001) and inversely with the percentage of type-IIB fibres (r=696; P<0.03).
      Incubation with isoprenaline (10 microM) for 30 min decreased the density of beta
      adrenergic receptors in the cell surface from 32.9+/-0.8 to 19.3+/-0.7 fmol mg
      dw(-1) in the soleus and from 16.8+/-1.0 to 12.0+/-0.7 fmol mg dw(-1) in the
      epitrochlearis. Internalisation appeared rapid (half-time less than 5 min). To
      study externalisation of beta-adrenergic receptors, soleus strips were incubated
      30 min with 10 microM isoprenaline and then transferred to buffer without
      agonist. The first incubation reduced the density to approximately 50%, the
      subsequent incubation without agonist increased cell surface receptor density to
      approximately 80% of the initial density after 1 h. No further increase was
      observed over the next 2 h, suggesting that some of the receptors had been
      degraded. Insulin or contractile activity did not influence rate of
      externalisation.

PMID- 11976936
TI  - Influence of nasotrigeminal afferents on medullary respiratory neurones and upper
      airway patency in the rat.
AB  - Noxious stimulation of the nasal mucosa evokes a nasotrigeminal reflex (diving
      response), consisting of apnoea, bradycardia and vasoconstriction. However, the
      central mechanisms underlying the respiratory component remain unclear. Here, we
      describe the influence of nasotrigeminal stimulation (NS) on different types of
      ventral medullary respiratory neurones and upper airway patency in the rat. In an
      arterially perfused working heart-brainstem preparation (WHBP), NS was induced by
      either irrigation of the nasal passage with cold saline (100-200 microl) or
      electrical stimulation of the trigeminal ethmoidal nerve (EN5, 20 Hz, 10 s, 100
      micros, 0.5-2 V). Both stimuli evoked apnoea, bradycardia, a pressor response,
      persistent discharge in the recurrent laryngeal nerve and marked glottal
      adduction (P<0.001). NS evoked a distinct pattern of response in respiratory
      neurones: inspiratory (I) neurones ceased firing and hyperpolarized (n=19), while
      postinspiratory neurones depolarized (n=10) and discharged persistently. The
      latency of EN5-evoked synaptic responses (excitatory to postinspiratory neurones
      12.3+/-2.8 ms, n=10; inhibitory to inspiratory neurones 11.8+/-1.9 ms; n=19) was
      comparable. During the NS-evoked apnoea burst discharges were superimposed on a
      maintained level of tonic activity recorded from both the recurrent laryngeal
      nerve (n=4) and some postinspiratory neurones (n=7). The physiological
      significance of these "apnoeic rhythms" is discussed. We conclude that the
      cardiorespiratory components of the diving response are mediated by activation of
      distinct sets of postinspiratory respiratory neurones.

PMID- 11976935
TI  - Mechanisms for the inhibition of amiloride-sensitive Na+ absorption by
      extracellular nucleotides in mouse trachea.
AB  - Purinergic stimulation of airway epithelial cells induces Cl- secretion and
      modulates Na+ absorption by an unknown mechanism. To gain insight into this
      mechanism, we used a perfused micro-Ussing chamber to assess transepithelial
      voltage (V(te)) and amiloride-sensitive short-circuit current (I(sc-Amil)) in
      mouse trachea. Exposure to apical ATP or UTP (each 100 micromol/l) caused a large
      initial increase in lumen negative V(te) and I(sc), corresponding to a transient
      Cl- secretion, while basolateral application of ATP/UTP induced only a small
      secretory response. Luminal, but not basolateral, application of nucleotides was
      followed by a sustained and reversible inhibition of I(sc-Amil) that was
      independent of extracellular Ca2+ or activation of protein kinase C and was not
      induced by carbachol (100 micromol/l) or the Ca2+ ionophore ionomycin (1
      micromol/l). Removal of extracellular Cl- or exposure to 200 microM DIDS reduced
      UTP-mediated inhibition of I(sc-Amil) substantially. The phospholipase inhibitor
      U73122 (10 micromol/l) and pertussis toxin (PTX; 200 ng/ml) both attenuated UTP
      induced Cl- secretion and inhibition of I(sc-Amil). Taken together, these data
      imply a contribution of Cl- conductance and PTX-sensitive G proteins to
      nucleotide-dependent inhibition of the amiloride-sensitive Na+ current in the
      mouse trachea.

PMID- 11976938
TI  - Role of the haem oxygenase-carbon monoxide pathway in insulin-induced
      hypothermia: evidence for carbon monoxide involvement.
AB  - A reduction of body temperature (T(b)) is a phenomenon concomitant with
      hypoglycaemia in mammals. Haem oxygenase (HO) catalyses the metabolism of haem to
      biliverdin, free iron and carbon monoxide (CO). Recently, the HO pathway has been
      shown to play an important role in thermoregulation. The present study was
      designed to test the hypothesis that the HO pathway plays a role in insulin
      induced hypothermia and that CO, rather than free iron or biliverdin, is the HO
      product involved in this response. Body temperature (T(b)) of Wistar rats was
      measured by biotelemetry. Infusion of insulin (0.2 U/kg per h, i.v.) caused a
      significant drop in T(b). Intracerebroventricular (i.c.v.) administration of zinc
      deuteroporphyrin 2,4-bis glycol (ZnDPBG, a HO inhibitor, 200 nmol) combined with
      saline infusion had no effect on T(b) but increased insulin-induced hypothermia
      significantly. The i.c.v administration of neither the iron chelator deferoxamine
      (250 microg) nor biliverdin (152 nmol) altered the hypothermic response to
      insulin, whereas CO-saturated saline significantly reduced insulin-induced
      hypothermia. These data indicate that the HO pathway prevents excessive drops in
      T(b) in insulin-induced hypothermia. Because biliverdin and iron had no effect,
      while CO significantly reduced the hypothermic response elicited by insulin
      infusion, these data imply that CO is the HO product involved in the
      thermoregulatory effect of insulin-induced hypothermia.

PMID- 11976937
TI  - Inhibition of mitochondrial function affects cellular Ca2+ handling in pancreatic
      B-cells.
AB  - The mitochondrial inhibitors NaN(3) and carbonyl cyanide p
      (trifluoromethoxy)phenylhydrazone (FCCP) were used to study the role of
      mitochondria in pancreatic B-cell Ca2+ homeostasis. In glucose-stimulated B-cells
      NaN(3) and FCCP both increased the K(ATP) current and thus hyperpolarized the
      cell membrane potential, as expected for agents depleting cellular ATP. NaN(3)
      and FCCP stopped the glucose-induced oscillations in the cytosolic free Ca2+
      concentration ([Ca2+](c)) and elicited a biphasic response. After a first rapid
      and transient increase, [Ca2+](c) rose in a second slow phase to a sustained
      level. In cells pretreated with thapsigargin the first inhibitor-induced rise in
      [Ca2+](c) was absent, suggesting that it may be due to Ca2+ mobilization from
      intracellular stores. The glucose-induced oscillations were terminated again by
      NaN(3) and FCCP, respectively, but the slow increase in [Ca2+](c)of the second
      phase was still present. A minute increase in [Ca2+](c)elicited by NaN(3) or FCCP
      was even visible after the removal of extracellular Ca2+, suggesting that the
      inhibitors also mobilize Ca2+ from mitochondria. NaN(3) and FCCP induced Ca2+
      influx into B-cells treated with low glucose concentrations whose voltage
      dependent Ca2+ channels are closed. Experiments with thapsigargin-preincubated
      cells indicate that disturbance of mitochondrial function stimulates Ca2+ influx
      through voltage-independent Ca2+ pathways. During the NaN(3)-induced increase in
      [Ca2+](c), K+-elicited depolarizations of the cells did not further augment
      [Ca2+](c). Evidently, this is due to a direct inhibitory effect of azide on L
      type Ca2+ channels. The data demonstrate that disturbing the mitochondrial
      function affects cellular Ca2+ homeostasis in B-cells at several sites. Thus, it
      is concluded that intact mitochondrial function is a prerequisite for regular
      Ca2+ handling in B-cells.

PMID- 11976939
TI  - Dual regulation of cardiac Na+-K+ pumps and CFTR Cl- channels by protein kinases
      A and C.
AB  - Regulation of Na+-K+ pump current (I(p)) and cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl- current (I(CFTR)) by protein kinases A and C
      (PKA and PKC) was compared under identical experimental conditions by
      simultaneous measurement of the two currents in guinea-pig ventricular myocytes
      whole-cell voltage-clamped at 30-32 degrees C. Membrane current (I) was monitored
      at a holding potential (V) of -20 mV. I/ V relationships were obtained by
      hyperpolarizing voltage ramps. Phorbol 12,13-dibutyrate (PDBu, 0.1-1 microM) and
      chelerythrine (10 microM) were used to stimulate and inhibit, respectively, PKC
      activity. PKA was stimulated by forskolin (4 microM) and inhibited by H-89 (50
      microM). At -20 mV, stimulation of PKC by PDBu increased I(p) to 121-123% of
      control. Addition of chelerythrine completely reversed this effect. The PDBu
      induced augmentation of I(p) was voltage dependent. The ratio I(p)(PDBu)/
      I(p)(control) increased from 1.10 at -100 mV to ~1.35 at positive membrane
      potentials. Stimulation of PKA by forskolin also increased I(p) voltage
      dependently (128% of control at -20 mV). The effects of PKC and PKA stimulation
      on I(p) were additive. The maximum I(p) observed in the presence of PDBu and
      forskolin was 141% of control. Application of either H-89 or chelerythrine
      reversibly decreased I(p) by 40% and 24%, respectively, suggesting that basal PKA
      and PKC activities were involved in the regulation of I(p). In the presence of H
      89, PDBu was unable to increase I(p). Likewise, pre-application of chelerythrine
      abolished the forskolin-induced augmentation of I(p). In contrast to I(p),
      I(CFTR) (measured simultaneously) was absent under basal conditions. Stimulation
      of PKA by forskolin activated a pronounced I(CFTR). Stimulation of PKC by PDBu,
      on the other hand, neither activated the Cl(-) current significantly nor
      increased I(CFTR) pre-activated by forskolin. Inhibition of PKC by chelerythrine,
      however, attenuated the PKA-mediated activation of I(CFTR). The results reveal a
      complex interplay between PKA and PKC in regulating cardiac I(p) and I(CFTR) with
      some similarities but also important differences. I(p) is increased voltage
      dependently and additively by stimulation of both kinases. The steady-state
      activity of each of the kinases is involved in the modulation of basal I(p) and
      obligatory for the augmentation of I(p) induced by stimulation of the other
      kinase. In contrast, there appears to be no basal I(CFTR). I(CFTR) is activated
      significantly only after stimulation of PKA. PKC activity, however, appears to
      facilitate this activation.

PMID- 11976940
TI  - Kinetics and Gbetagamma modulation of Ca(v)2.2 channels with different auxiliary
      beta subunits.
AB  - Modulation of calcium channels by both auxiliary subunits and G proteins was
      studied in cell-attached patches from COS-7 cells transfected with Ca(v)2.2
      channel subunits (N-type, alpha(1)B and either beta(1b) or beta(2a)). These were
      co-expressed with either Gbeta(1)gamma(2) or the Gbetagamma-binding domain of
      beta-adrenergic-receptor kinase-1 to sequester endogenous Gbetagamma. Since G
      protein modulation of Ca(v) channels may affect both inactivation and activation,
      we examined Gbetagamma modulation of Ca(v)2.2 channels in the presence of two
      different beta-subunits that affect inactivation differently and compared in
      detail the single-channel characteristics of N-type channels expressed with
      either of these beta-subunit isoforms. The single-channel mean amplitude and mean
      open time were not influenced by the transfection combination. However, the mean
      closed time at +40 mV was increased for both beta(1b) and beta(2a)-subunits by co
      transfection with Gbeta(1)gamma(2). This effect was absent at lower voltages as
      examined for channels with the beta(1b)-subunit. The distribution of latency-to
      first-opening of Ca(v)2.2 channels was similar for both beta-subunit isoforms.
      However, the inclusion of the beta(2a) subunit resulted in channels with an
      additional, prominent, slow activation phase. Co-transfection of Gbeta(1)gamma(2)
      with Ca(v)2.2 channels markedly reduced the ensemble current amplitude and slowed
      the first latency. The inhibition imposed by Gbeta(1)gamma(2) was largely
      independent of the beta-subunit species. Facilitation of Gbetagamma-modulated
      currents (the channel response following a large and brief depolarising prepulse)
      was observed for channels with both beta-subunits and involved mainly enhancement
      of the activation, as assessed by the faster first latency. The inactivation
      process was strongly dependent on the beta-subunit species, with beta(1b)
      supporting inactivation and beta(2a) reducing this process. This difference was
      assessed by estimation of both steady-state inactivation (prepulse influence on
      test pulse responses) and the inactivation time course during depolarisation. At
      +40 mV, channels with the beta(1b)-subunit had a fast component of inactivation
      (time constant ~180 ms, 50%) and a slow phase with time constant of approximately
      1 s, while the beta(2a)-subunit supported only a very slow inactivation process
      with time constant of approximately 5 s. Co-transfection of Gbeta(1)gamma(2) with
      the Ca(v)2.2 channel had no effect on the inactivation properties with either
      beta-subunit. In summary, we show that the inactivation properties of expressed
      Ca(v)2.2 channels depend largely on the beta-subunit species and to a minor
      extent only on the presence or absence of the Gbetagamma modulator. Furthermore,
      the activation, amplitude, mean open and closed times and G protein modulation of
      N-type channels were similar for both beta(1b)- and beta(2a)-subunits.

PMID- 11976941
TI  - Myosin light chain kinase modulates hypotonicity-induced Ca2+ entry and Cl-
      channel activity in human cervical cancer cells.
AB  - Hypotonicity-induced Ca2+ entry is a critical signal for the normal regulatory
      volume decrease in human cervical cancer cells. The aim of this study was to
      explore the role of myosin light chain kinase (MLCK) in the regulation of
      hypotonicity-induced Ca2+ signalling and Cl- channel activity. Blockade of MLCK
      activity by MLCK(11-19) amide, a substrate-specific peptide inhibitor, markedly
      attenuated hypotonicity-induced Ca2+ entry. A similar result was obtained with ML
      7, a synthetic naphthalenesulphonyl derivative that inhibits the binding of ATP
      to MLCK. More than 85% of the activity of the volume-regulated Cl- channel was
      suppressed when intracellular Ca2+ was buffered to near zero in the absence of
      extracellular Ca2+, suggesting that hypotonicity-induced Ca2+ signalling is
      important for the activation of the volume-regulated Cl- channel. Intracellular
      dialysis with MLCK(11-19) amide or ML-7 concentration-dependently reduced the
      amplitude and rate of activation of the volume-regulated Cl- channel. Swelling
      activated taurine transport was also inhibited concentration dependently by ML-7
      and MLCK(11-19) amide with IC(50) values of 6.4 and 2.0 microM, respectively.
      Hypotonicity induced MLC phosphorylation which was mediated totally by MLCK and
      depended on Ca2+ entry. However, phosphorylated MLC per se was not involved
      critically in the regulation of Ca2+ entry and activation of volume-sensitive
      organic osmolyte/anion channels (VSOAC). We propose that MLCK has a novel
      function in regulating the activation of VSOAC by mediating Ca2+ entry in
      response to hypotonicity. This function of MLCK on Ca2+ signalling does not
      correlate with MLC phosphorylation.

PMID- 11976942
TI  - Nuclear pore ion channel activity in live syncytial nuclei.
AB  - Nuclear pore complexes (NPCs) are important nanochannels for the control of gene
      activity and expression. Most of our knowledge of NPC function has been derived
      from isolated nuclei and permeabilized cells in cell lysates/extracts. Since
      recent patch-clamp work has challenged the dogma that NPCs are freely permeable
      to small particles, a preparation of isolated living nuclei in their native
      liquid environment was sought and found: the syncytial nuclei in the water of the
      coconut Cocos nucifera. These nuclei have all properties of NPC-mediated
      macromolecular transport (MMT) and express foreign green fluorescent protein
      (GFP) plasmids. They display chromatin movement, are created by particle
      aggregation or by division, can grow by throwing filaments to catch material,
      etc. This study shows, for the first time, that living NPCs engaged in MMT do not
      transport physiological ions - a phenomenon that explains observations of
      nucleocytoplasmic ion gradients. Since coconuts are inexpensive (less than
      US$1/nut per litre), this robust preparation may contribute to our understanding
      of NPCs and cell nucleus and to the development of biotechnologies for the
      production of DNA, RNA and proteins.

PMID- 11976943
TI  - Hepatic arterial perfusion decreases intrahepatic shunting and maintains glucose
      uptake in the rat liver.
AB  - Intrahepatic shunts have an important function in the regulation of portal venous
      pressure in the normal rat liver. The present study determined their location,
      the region of confluence between the hepatic arterial and portal venous
      vasculatures, regions within the liver that are bypassed and the effects of
      hepatic arterial perfusion upon the intrahepatic redistribution of portal venous
      flow. Livers of male Sprague-Dawley rats were excised and perfused in vitro.
      Hepatic bromosulphthalein (BSP) and glucose uptake were measured in hepatic
      venous samples. Diversion of the hepatic arterial supply into the portal venous
      vasculature opened the portal venous intrahepatic shunts and resulted in a 50%
      reduction in portal venous glucose uptake from 29.6+/-1.6% to 14.9+/-0.9% (
      P<0.0001 Student's paired t-test). Portal venous injection of 15-microm-diameter
      microspheres also opened the intrahepatic shunts and reduced portal venous
      glucose uptake to 10% from 29.0+/-1.6% to 7.8+/-0.9% ( P<0.0001 Student's paired
      t-test). No significant reductions in portal venous BSP uptake (43.0+/-6.9 to
      48.0+/-4.8%) or hepatic arterial glucose uptake, from an average value of 94.0%,
      occurred. Therefore, cessation of hepatic arterial perfusion or portal venous
      injection of microspheres reduced portal venous glucose uptake without affecting
      BSP uptake. It is concluded that intrahepatic shunts divert perfusate away from
      the perivenous, sinusoidal (zone III) regions and into the hepatic venous
      vasculature, distal to zone III. The microsphere data indicate that confluence
      between the hepatic arterial and portal venous vasculatures occurs mainly in
      sinusoidal zone II.

PMID- 11976948
TI  - A new family of cyclophilins with an RNA recognition motif that interact with
      members of the trx/MLL protein family in Drosophila and human cells.
AB  - A new family of cyclophilins with an RNA recognition motif (RRM) has members in
      vertebrates, roundworms and flatworms. We have identified a
      Drosophilacyclophilin, Dcyp33, with a high degree of amino acid sequence identity
      and similarity with other members of the family. Dcyp33 interacts through its RRM
      domain with the third PHD finger of trithorax. This interaction is conserved in
      the human homologues of these proteins, Cyp33 and MLL. Over expression of Dcyp33
      in DrosophilaSL1 cells results in down-regulation of AbdominalB Hoxgene
      expression, mirroring the effect of human Cyp33 on the expression of human
      HOXgenes.

PMID- 11976949
TI  - Analysis of the expression pattern of Mysidium columbiae wingless provides
      evidence for conserved mesodermal and retinal patterning processes among insects
      and crustaceans.
AB  - The Wnt family includes a number of genes, such as wingless ( wg), which encode
      secreted glycoproteins that function in numerous developmental patterning
      processes. In order to gain a better understanding of crustacean pattern
      formation, a wg orthologue was cloned from the malacostracan crustacean Mysidium
      columbiae(mysid), and the expression pattern of this gene was compared with that
      of Drosophila wg. Although Drosophila wg is expressed in many developing tissues,
      such as the ventral neuroectoderm, M. columbiae wg (mcowg)expression is detected
      within only a subset of these tissues. mcowg is expressed in the dorsal part of
      each developing segment and within the developing eye, but not within the ventral
      neuroectoderm. Dorsal wg expression in Drosophila is required for heart and
      muscle development, and conservation of this dorsal wgexpression pattern suggests
      that mcowgmay function to pattern these tissues in mysids. Consistent with this,
      expression of Even-skipped (Eve) protein in heart precursor and muscle cells,
      which is dependent on Wg signaling in Drosophila, is also conserved in mysids.
      Within the developing mysid eye, mcowg is expressed in a pattern that is similar
      to the expression pattern of Drosophila wg in the fly eye disc. In Drosophila,Wg
      inhibits neural differentiation at the anterior margin of the eye disc and
      patterns the dorsal/ventral axis of the eye. These data indicate that mcowg may
      function similarly during mysid eye development. Analysis of mcowgexpression
      provides molecular evidence suggesting that the processes of heart, muscle, and
      eye patterning are likely to be conserved among insects and crustaceans.

PMID- 11976950
TI  - Evolutionary conservation and association of SPARC with the basal lamina in
      Drosophila.
AB  - SPARC (secreted protein, acidic, rich in cysteine, also called BM40 and
      osteonectin) is a multifunctional calcium-binding glycoprotein whose modular
      organization has been highly conserved between invertebrates and vertebrates,
      indicating a conservation of function during metazoan evolution. Genome analysis
      has revealed a single copy of the DrosophilaSPARC ( dSPARC) gene. As a first step
      towards investigating the function of SPARC in Drosophila, we examined its
      spatiotemporal distribution during development. During embryogenesis, dSPARC mRNA
      transcripts are restricted to mesoderm derivatives, hemocytes, and the fat body.
      Immunostaining with anti- DrosophilaSPARC antibodies indicates that dSPARC
      secreted by the hemocytes and fat body cells is concentrated in basal laminae
      surrounding internal organs. During oogenesis, dSPARC transcripts are restricted
      to the somatic cells of the germarium and follicles. Consistent with embryonic
      development, the resultant protein is concentrated in basal laminae. Mutations in
      type IV collagen are associated with a dramatic decrease in dSPARC protein
      immunostaining in hemocytes. The data suggest that the production and assembly of
      dSPARC in the basal lamina is dependent on type IV collagen, and raise the
      possibility that dSPARC and type IV collagen interactions are a prerequisite to
      the assembly and structural integrity of basal laminae in Drosophila.

PMID- 11976951
TI  - A conserved F-box gene with unusual transcript localization.
AB  - Drosophila partner of paired ( ppa), which encodes an F-box protein that targets
      the Pax transcription factor Paired (Prd) for degradation, has the striking
      property that its mRNA is expressed in a striped pattern with a characteristic
      registration relative to the striped expression of prd in early embryos.
      Localized expression of F-box genes was not expected because F-box proteins
      generally have multiple substrates. We hypothesize that the patterned mRNA
      expression of Drosophila and zebrafish ppa homologs may reflect constraints
      resulting from the localized expression of their degradation substrates. To begin
      to test this idea, we wished to determine whether patterned mRNA expression is
      commonly observed among F-box genes, or whether it might be peculiar to ppa and
      its homologs, or even specific to Drosophila. We examined embryonic expression of
      all predicted F-box genes in Drosophila and found that mRNAs of 21 out of 23
      predicted F-box genes are expressed uniformly in early Drosophila embryos,
      whereas ppa and CG4911 mRNAs are patterned, CG4911 being expressed at the
      positions of gastrulation folds. We also identified and tested expression of ppa
      in zebrafish, which has two highly conserved homologs, ppaA and ppaB, and found
      that both are expressed during embryogenesis and have enriched mRNA expression in
      regions including the neural tube, the head, and the fin buds. Despite being
      unusual in having localized transcripts, we found that the Drosophila and
      zebrafish homologs interact with the expected Drosophila components of the
      cellular degradation machinery - Skp1 (SkpA) and Rbx1 (Roc1a) - suggesting that
      the Ppa proteins are indeed functional F-box proteins. We conclude that
      patterning of ppa mRNA could reflect a constraint on ppa function that is not
      common among F-box genes. Electronic supplementary material to this paper can be
      obtained by using the Springer LINK server located at
      http://dx.doi.org/10.1007/s00427-002-0222-7.

PMID- 11976952
TI  - Mox homeobox expression in muscle lineage of the gastropod Haliotis asinina:
      evidence for a conserved role in bilaterian myogenesis.
AB  - Mox homeobox genes are expressed during early vertebrate somitogenesis. Here we
      describe the expression of Has-Mox, a Mox gene from the gastropod Haliotis
      asinina. Has-Moxis expressed in the trochophore larva in paraxial mesodermal
      bands. During larval development, Has-Mox expression remains restricted to
      mesodermal cells destined to form adult muscle in the foot. This restricted
      expression of Has-Mox in Haliotis is similar to that observed for vertebrate Mox
      genes, suggesting a conserved role in myogenesis in deuterostomes and
      lophotrochozoans. In contrast, Mox is not expressed in muscle lineages in the
      ecdysozoan representatives Caenorhabditis elegans or Drosophila; the C.
      elegansgenome has lost Mox altogether. Electronic supplementary material to this
      paper can be obtained by using the Springer Link server located at
      http://dx.doi.org/10.1007/s00427-002-0223-6.

PMID- 11976953
TI  - Heat-inducible transgenic expression in the silkmoth Bombyx mori.
AB  - Germline transformation with new transposon vectors now enables causal tests of
      gene function via ectopic protein expression or RNA interference in non
      drosophilid insects. The problem remains of how to drive the transgene expression
      in vivo. We employed germline transformation using the piggyBac 3xP3-EGFP vector
      to test whether the Drosophila heat shock hsp70 promoter will be active in the
      live silkworm. We modified the original vector by cloning the coding sequence for
      Bombyx nuclear receptor Ftz-F1 between the hsp70 promoter and the terminator.
      Three independent transgenic lines expressing the Pax-6-driven EGFP marker in
      larval and adult photoreceptors were obtained with efficiencies of up to 1.7% of
      fertile G0 adults that gave GFP-positive progeny. Chromosomal integration of the
      transposon was confirmed with inverse PCR. Heat induction of the transgenic BmFtz
      F1 was proven at both the mRNA and protein levels. RT-PCR data showed that the
      Drosophila heat shock promoter was functional in all three transgenic lines.
      Although basal activity was apparent at 25 degrees C, 1 h at 42 degrees C induced
      BmFtz-F1 mRNA at different stages of development and in diverse tissues. The
      relative levels of induction differed among the transgenic lines. Northern blot
      hybridization detected transgenic BmFtz-F1 only after heat shock and low levels
      of the mRNA were still present 6 h after the heat treatment. Immunostaining of
      epidermis using anti-BmFtz-F1 antibody showed a clear increase of nuclear signal
      90 min after a heat shock.

PMID- 11976954
TI  - The Drosophila Pipsqueak protein defines a new family of helix-turn-helix DNA
      binding proteins.
AB  - Many prokaryotic and eukaryotic DNA-binding proteins use a helix-turn-helix (HTH)
      structure for DNA recognition. Here we describe a new family of eukaryotic HTH
      proteins, the Pipsqueak (Psq) family, which includes proteins from fungi, sea
      urchins, nematodes, insects, and vertebrates. Three subgroups of the Psq family
      can be distinguished. Like the HTH proteins of the prokaryotic resolvase family,
      members of the CENP-B/transposase subgroup catalyze site-specific recombination
      reactions. This functional conservation, together with a primary sequence
      similarity between the resolvase and Psq DNA-binding domains, suggests that the
      resolvase and Psq families are evolutionarily linked. More than half of the newly
      identified Drosophila Psq proteins contain a BTB protein-protein interaction
      domain. All proteins of this BTB subgroup belong to the conserved Tramtrack group
      of BTB-domain proteins. About half of the members of the Tramtrack group contain
      a Psq domain, while the other half is made up of proteins that contain a zinc
      finger domain. Thus, nearly all members of this group appear to be DNA-binding
      proteins. Among other developmental regulators, the Drosophila cell death protein
      E93 was found to contain a Psq motif and to define a third subgroup of Psq domain
      proteins. The high sequence conservation of the E93 Psq motif allowed the
      identification of E93 orthologs in humans and lower metazoans.

PMID- 11976956
TI  - Expression of the Idefix retrotransposon in early follicle cells in the germarium
      of Drosophila melanogaster is determined by its LTR sequences and a specific
      genomic context.
AB  - Retrotransposons are transcriptionally activated in different tissues and cell
      types by a variety of genomic and environmental factors. Transcription of LTR
      retrotransposons is controlled by cis-acting regulatory sequences in the 5' LTR.
      Mobilization of two LTR retroelements, Idefix and ZAM, occurs in the unstable
      RevI line of Drosophila melanogaster, in which their copy numbers are high, while
      they are low in all other stocks tested. Here we show that both a full-length and
      a subgenomic Idefix transcript that are necessary for its mobilization are
      present in the Rev1 line, but not in the other lines. Studies on transgenic
      strains demonstrate that the 5' LTR of Idefix contains sequences that direct the
      tissue-specific expression of the retroelement in testes and ovaries of adult
      flies. In ovaries, expression occurs in the early follicle and in other somatic
      cells of the germarium, and is strictly associated with the unstable genetic
      context conferred by the RevI line. Control of tissue-specific Idefix expression
      by interactions between cis-acting sequences of its LTR and trans-acting genomic
      factors provides an opportunity to use this retroelement as a tool for the study
      of the early follicle cell lineage in the germarium.

PMID- 11976957
TI  - Development of a high-throughput yeast two-hybrid screening system to study
      protein-protein interactions in plants.
AB  - We have developed a high-throughput yeast two-hybrid screening system (HTP-YTH)
      that incorporates yeast gap-repair cloning, multiple positive ( ADE2, HIS3, lacZ)
      and negative ( URA3-based) selection schemes to reduce the incidence of negative
      and false positive clones, and automation of laboratory procedures to increase
      throughput. This HTP-YTH system has been applied to the study of protein-protein
      interactions that are involved in rice defense signal transduction pathways. More
      than 100 genes involved in plant defense responses were selected from DuPont's
      rice expressed sequence tag (EST) databases as baits for HTP-YTH screening.
      Results from YTH screening of eight of these rice genes are presented in this
      paper. Not only have we identified known protein-protein interactions, but we
      have also discovered novel interactions, which may ultimately reveal the
      regulatory network of host defense signal transduction pathways. We have
      demonstrated that our HTP-YTH method can be used to map protein-protein
      interaction networks and signal transduction pathways in any system. In
      combination with other approaches, such efficient YTH screens can help us
      systemically to study the functions of known and unknown genes in the genomics
      era.

PMID- 11976958
TI  - Identification of early-responsive genes associated with the hypersensitive
      response to tobacco mosaic virus and characterization of a WRKY-type
      transcription factor in tobacco plants.
AB  - In order to identify genes that are involved in the defense reaction against
      pathogen attack, we screened for examples that are regulated during the
      hypersensitive response (HR) to infection by tobacco mosaic virus (TMV) of
      tobacco ( Nicotiana tabacum cv. Xanthi nc) carrying the N gene, which confers
      resistance to TMV. Among seven genes initially identified by fluorescent
      differential display, one clone was further characterized because its transcripts
      accumulated rapidly and transiently after the onset of HR. Its full-length cDNA
      of 1346 bp encoded a polypeptide consisting of 258 amino acids. The deduced
      protein contained a single WRKY domain, a Cys(2)His(2) zinc-finger motif and a
      leucine-zipper motif, showing high similarity to WIZZ, a member of the family of
      WRKY transcription factors in tobacco. The gene was thus designated TIZZ. A GFP
      TIZZ fusion protein was found to localize to the nucleus upon introduction into
      epidermal cells of onion. Bacterially expressed TIZZ was able to bind to the W
      box (TTGAC) element that is recognized by other WRKY proteins, but
      transactivation assays showed it to be unable to activate reporter gene
      expression by itself. TIZZ transcripts were induced in TMV-infected nahG
      transgenic tobacco plants, in which salicylic acid fails to accumulate. Neither
      exogenously applied salicylic acid nor mechanical wounding induced TIZZ
      transcript accumulation. These results indicate the presence of salicylic acid
      independent pathways for HR signal transduction, in which a novel type of WRKY
      protein(s) may play a critical role for the activation of defense.

PMID- 11976959
TI  - Identification of the N-acetyl-D-glucosamine-inducible element in the promoter of
      the Trichoderma atroviride nag1 gene encoding N-acetyl-glucosaminidase.
AB  - We have investigated the regulation by N-acetyl-glucosamine of the nag1 gene of
      the mycoparasitic biocontrol fungus Trichoderma atroviride (= T. harzianum P1),
      which encodes a 73-kDa N-acetyl-beta-D-glucosaminidase. The use of translational
      fusions revealed that a 290-bp fragment of the 5' regulatory region of nag1 is
      sufficient to confer inducibility on the Aspergillus niger goxA gene. The region
      between positions -150 and -290, upstream of the nag1 coding region, was
      investigated using in vivo methylation protection analysis and electrophoretic
      mobility shift assays (EMSAs). Two neighbouring regions that interacted with
      regulatory proteins were identified, and bases essential for these interactions
      were determined in vitro. These data reveal protein binding to a CCCCT element at
      -240, a CCAGN(13)CTGG motif at -284, and a CCAAT-box which is present in the
      spacer of the latter motif. Evidence for the binding of a Hap2/3/5 complex to
      this CCAAT motif is presented. Protein binding to all three motifs was
      constitutive, and no differences were observed between induced and non-induced
      cultures. Mutation of either the CCAGN(13)CTGG or the AGGGG motif resulted in
      loss of inducibility of nag1 expression by N-acetyl-D-glucosamine in vivo.

PMID- 11976960
TI  - Characterization of pECL18 and pKPN2: a proposed pathway for the evolution of two
      plasmids that carry identical genes for a Type II restriction-modification
      system.
AB  - The primary structures of the plasmids pECL18 (5571 bp) and pKPN2 (4196 bp) from
      Escherichia coli and Klebsiella pneumoniae, respectively, which carry genes for a
      Type II restriction-modification system (RMS2) with the specificity 5'-CCNGG-3',
      were determined in order to elucidate the structural relationship between them.
      The data suggest a possible role for recombination events at bom (basis of
      mobility) regions and the sites of resolution of multimer plasmid forms (so
      called cer sequences) in the structural evolution of multicopy plasmids. Analysis
      of the sequences of pECL18 and pKPN2 showed that the genes for RM* Ecl18kI and
      RM* Kpn2kI, and the sequences of the rep (replication) regions in the two
      plasmids, are almost identical. In both plasmids, these regions are localized
      between the bom regions and the cer sites. The rest of the pECL18 sequence is
      almost identical to that of the mob (mobilization) region of ColE1, and the
      corresponding segment of pKPN2 is almost identical to part of pHS-2 from Shigella
      flexneri. The difference in primary structures results in different mobilization
      properties of pECL18 and pKPN2. The complete sequences of pECL18, pKPN2 and the
      pairwise comparison of the sequences of pECL18, pKPN2, ColE1 and pHS-2 suggest
      that plasmids may exchange DNA units via site-specific recombination events at
      bom and cer sites. In the course of BLASTN database searches using the cer sites
      of pECL18 and pKPN2 as queries, we found twenty cer sites of natural plasmids.
      Alignment of these sequences reveals that they fall into two classes. The
      plasmids in each group possess related segments between their cer and bom sites.

PMID- 11976961
TI  - A novel ABC transporter gene, PMR5, is involved in multidrug resistance in the
      phytopathogenic fungus Penicillium digitatum.
AB  - We have cloned a novel ABC transporter gene PMR5 from the phytopathogenic fungus
      Penicillium digitatum by RT-PCR using degenerate primers. The deduced amino acid
      sequence of PMR5 showed 37% identity to PMR1 from the same fungus, 71% identity
      to AtrB from Aspergillus nidulans, and 65% identity to BcatrB from Botrytis
      cinerea. Disruption mutants for PMR5 were generated in two independent P.
      digitatum strains and their phenotypes were characterized. These mutants
      displayed increased sensitivity to thiabendazole (a benzimidazole), benomyl (a
      benzimidazole), dithianon (a quinone), resveratrol (the phytoalexin of grape),
      and camptothecin (an alkaloid). Delta pmr1 disruption mutants were previously
      reported to show resistance to demethylation inhibitors (DMIs). These mutants
      were found also to display increased sensitivity to phloretin (the phytoanticipin
      of apples), camptothecin and oligomycin (an antibiotic). Transcription of PMR1
      and PMR5 was strongly induced in response to several toxicants, including DMIs
      that specifically induced PMR1. In contrast, dithianon and resveratrol
      specifically induced PMR5 transcription. These findings indicate that expression
      of the two ABC transporter genes is regulated differently, and that they have
      complementary roles in multidrug resistance, with each having different substrate
      specificities.

PMID- 11976962
TI  - Genomic analysis of cultivated barley (Hordeum vulgare) using sequence-tagged
      molecular markers. Estimates of divergence based on RFLP and PCR markers derived
      from stress-responsive genes, and simple-sequence repeats (SSRs).
AB  - Three types of molecular markers have been compared for their utility in
      evaluating genetic diversity among cultivars of Hordeum vulgare. Restriction
      fragment length polymorphisms at 71 sites were scored with the aid of probes
      corresponding to stress-responsive genes from barley and wheat, coding for a low
      molecular-weight heat shock protein, a dehydrin, an aldose reductase homolog, and
      a 18.9-kDa drought-induced protein of unknown function. Indexes of genetic
      diversity computed in the total sample and within groups of cultivars (two-rowed
      and six-rowed, winter and spring varieties) indicated high values of genetic
      differentiation ( F (ST) >15%). A second assessment of genetic diversity was
      performed by PCR amplification of genomic DNA using as primers 13 arbitrary
      oligonucleotides derived from sequences of the same stress-responsive genes. A
      high degree of polymorphism was uncovered using these markers also, but they
      yielded low values for F (ST) (<7%) among groups of cultivars. Finally, 15
      different simple-sequence repeats (AC or AG) were amplified with primers based on
      unique flanking sequences. Levels of polymorphism and differentiation between
      groups of cultivars revealed by these markers were quite high. Ordination
      techniques applied to measures of genetic distance among cultivars demonstrated a
      remarkable ability of the RFLPs associated with stress-responsive genes to
      discriminate on the basis of growth habit. The correlation with production data
      for the cultivars in different environments was also significant. This
      "functional genomics" strategy was therefore as informative as the "structural
      genomics" (SSR-based) approach, but requires the analysis of fewer probes.

PMID- 11976963
TI  - Bacteriochlorophyll-dependent expression of genes for pigment-binding proteins in
      Rhodobacter capsulatus involves the RegB/RegA two-component system.
AB  - Expression of the puf and puc operons, which encode proteins of the
      photosynthetic apparatus of Rhodobacter capsulatus, is regulated by oxygen. A
      drop in the oxygen tension in the environment leads to an increase in the levels
      of puf and puc mRNAs. In strains lacking bacteriochlorophyll (Bchl) due to
      mutations in bch genes, the rise in puf and puc mRNA levels observed on reduction
      of oxygen tension is much less pronounced than in wild-type cells, indicating co
      regulation of the syntheses of pigments and pigment-binding proteins. Here we
      show that Bchl synthesis also affects the expression of the bchC gene, which
      codes for a subunit of bacteriochlorophyll synthase, suggesting an autoregulatory
      mechanism for the Bchl biosynthetic pathway. Furthermore, our data provide
      evidence that the RegB/RegA two-component system, which is known to play a
      central role in oxygen-controlled expression of photosynthesis genes, is also
      involved in the Bchl-dependent regulation. Mutant strains which do not synthesize
      RegB or RegA show similar oxygen-dependent puf and puc expression in the presence
      and absence of Bchl. Our results support the view that the RegB/RegA system can
      directly or indirectly sense whether Bchl synthesis takes place or not.

PMID- 11976964
TI  - Molecular characterization and chromosomal localization of cytochrome P450 genes
      involved in the biosynthesis of cyclic hydroxamic acids in hexaploid wheat.
AB  - The cyclic hydroxamic acids, 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) and 2,4
      dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), are defensive secondary
      metabolites found in gramineous plants including wheat, maize and rye. cDNAs for
      five cytochromes P450 (P450s) involved in DIBOA biosynthesis (CYP71C6, CYP71C7v2,
      CYP71C8v2, CYP71C9v1 and CYP71C9v2) were isolated from seedlings of hexaploid
      wheat [( Triticum aestivum L. cv. Chinese Spring (2n=6x=42, genomes AABBDD)] by
      RT-PCR and screening of a cDNA library. CYP71C9v1 and CYP71C9v2 are 97% identical
      to each other in amino acid and nucleotide sequences. The cloned P450 species
      showed 76-79% identity at the amino acid level to the corresponding maize P450
      species CYP71C1-C4, which are also required for DIBOA biosynthesis. The wheat
      P450 cDNAs were heterologously expressed in the yeast ( Saccharomyces cerevisiae)
      strain AH22. Microsome fractions from yeast cells expressing these P450 species
      catalyzed the same reactions as their maize orthologs. The chromosomes carrying
      the cyp71C6- C9v1 orthologs were identified by Southern hybridization using
      aneuploid lines of Chinese Spring wheat. The cyp71C9v1 orthologs were located on
      the chromosomes of wheat homoeologous group-4. The orthologs of the other P450
      genes, cyp71C7v2, cyp71C6 and cyp71C8v2, were located on group-5 chromosomes. The
      same P450 genes were also present in the three ancestral diploid species of
      hexaploid wheat, T. monococcum (AA), Aegilops speltoides [BB (approximately SS)]
      and Ae. squarrosa (DD).

PMID- 11976965
TI  - Cloning of a prolidase gene from Aspergillus nidulans and characterisation of its
      product.
AB  - Using EST sequence information available from the filamentous fungus Aspergillus
      nidulans as a starting point, we have cloned the prolidase-encoding gene,
      designated pepP. Introduction of multiple copies of this gene into the A.
      nidulansgenome leads to overexpression of an intracellular prolidase activity.
      Prolidase was subsequently purified and characterised from an overexpressing
      strain. The enzyme activity is dependent on manganese as a cofactor, is specific
      for dipeptides and hydrolyses only dipeptides with a C-terminal proline residue.
      Although these proline dipeptides are released both intracellularly and
      extracellularly, prolidase activity was detected only intracellularly.

PMID- 11976967
TI  - Characterization of three PDI-like genes in Physcomitrella patens and
      construction of knock-out mutants.
AB  - Plant genomes typically contain several sequences homologous to protein disulfide
      isomerase (PDI). PDI was first identified as an abundant enzyme in the
      endoplasmic reticulum, where it catalyzes the formation, reduction, and
      isomerization of disulfide bonds during protein folding. PDI-like proteins have
      also been implicated in a variety of other functions, such as the regulation of
      cell adhesion, and may act as elicitors of the autoimmune response in mammals. A
      PDI-like protein (RB60) was recently shown to be imported into chloroplasts in
      the unicellular green alga Chlamydomonas reinhardtii and a higher plant, Pisum
      sativum, where it associates with thylakoid membranes. This suggests that the
      different PDI-like proteins in plant and animals may have diverse biological
      roles. To begin to elucidate the roles of PDI-like proteins, we have cloned,
      characterized, and generated knock-out mutants for three PDI-like genes that have
      high, medium, and low levels of expression, respectively, in the moss
      Physcomitrella patens. Phylogenetic analysis indicates that the three PDI-like
      proteins cluster with RB60 and four proteins from Arabidopsis thaliana. They are
      typified by an N-terminal domain rich in negatively charged residues. The knock
      out mutants, which are the first knock-outs available for PDI-like proteins in a
      multicellular organism, were found to be viable, indicating that the function of
      each single gene is dispensable, and suggesting that they may be functionally
      complementary.

PMID- 11976966
TI  - Loss of the mitochondrial cox2 intron 1 in a family of monocotyledonous plants
      and utilization of mitochondrial intron sequences for the construction of a
      nuclear intron.
AB  - The intron content of plant organellar genes is a useful marker in molecular
      systematics and evolution. We have tested representatives of a wide range of
      monocotyledonous plant families for the presence of an intron (cox2 intron 1) in
      one of the most conservative mitochondrial genes, the cox2 locus. Almost all
      species analyzed were found to harbor a group II intron at a phylogenetically
      conserved position. The only exceptions were members of a single monocot family,
      the Ruscaceae: representatives of all genera in this family were found to lack
      cox2 intron 1, but instead harbor an intron in the 3' portion of the cox2 coding
      region (cox2 intron 2). The presence of cox2 intron 1 in families of
      monocotyledonous plants that are closely related to the Ruscaceae suggests that
      loss of the intron is specific to this family and may have accompanied the
      evolutionary appearance of the Ruscaceae. Interestingly, sequences that are
      highly homologous to cox2 intron 2 are found in a nuclear intron in a lineage of
      monocotyledonous plants, suggesting that the originally mitochondrial group II
      intron sequence was transferred to the nuclear genome and reused there to build a
      spliceosomal intron.

PMID- 11976968
TI  - Molecular and biochemical characterization of the Neurospora crassa glycogen
      synthase encoded by the gsn cDNA.
AB  - Glycogen synthases catalyze the transfer of a glucosyl moiety from a nucleotide
      phosphosugar to a nascent glycogen chain via an alpha1-->4 linkage. Although many
      genes coding for glycogen synthases have been described, the enzymes from rabbit
      and yeast are the best characterized. The fungus Neurospora crassa accumulates
      glycogen during exponential growth, and mobilizes it at the onset of stationary
      phase, or when placed at high temperature or starved for carbon. Through a PCR
      methodology, the gsn cDNA coding for the N. crassa glycogen synthase was
      isolated, and the amino acid sequence of the protein was deduced. The product of
      the cDNA seems to be the only glycogen synthase present in N. crassa.
      Characterization of the gsn cDNA revealed that it codes for a 706-amino acids
      protein, which is very similar to mammalian and yeast glycogen synthases. Gene
      expression increased during exponential growth, reaching its maximal level at the
      end of the exponential growth phase, which is consistent with the pattern of
      glycogen synthase activity and glycogen level. Expression of the gsn is highly
      regulated at the transcriptional level. Under culture conditions that induce heat
      shock, conidiation, and carbon starvation, expression of the gsn gene was
      decreased, and glycogen synthase activity and glycogen content behaved similarly.

PMID- 11976969
TI  - Cell cycle-dependent modulation of FtsZ expression in synchronized tobacco BY2
      cells.
AB  - In higher plants, the FtsZ protein, the ancestor of tubulin, has been shown to be
      implicated in both proplastid division, which occurs in dividing cells and in the
      division of the differentiated plastids present in non-dividing cells. Here we
      report studies on the expression of the two FtsZ gene families in higher plants,
      FtsZ1 and FtsZ2, in non-synchronized and synchronized tobacco BY2 cells. We have
      isolated and characterized members of each gene family from Nicotiana tabacum.
      Specific cDNA probes for each tobacco FtsZ gene family and polyclonal antibodies
      specific for the FtsZ1 and FtsZ2 proteins were obtained in order to determine
      mRNA and protein levels. A constant level of FtsZ1 and FtsZ2 transcripts and
      proteins was observed in non-synchronized cell cultures. However, a complex
      pattern of expression of both gene families was observed during the cell cycle in
      synchronized cells, with mRNA and protein levels peaking during cell division,
      thus implying that the FtsZ proteins may be involved in plastid transmission to
      the two daughter cells.

PMID- 11976970
TI  - C-to-U conversion in the intercistronic ndhI/ ndhG RNA of plastids from monocot
      plants: conventional editing in an unconventional small reading frame?
AB  - Editing of plastid RNAs proceeds by C-to-U, in hornwort species also by extensive
      U-to-C, transitions, which predominantly lead to the restoration of codons for
      structurally and/or functionally important, conserved amino acid residues. So
      far, only one instance of editing outside coding regions has been reported - in
      the psbL/ psbF intergenic region of Ginkgo biloba. This site was proposed to have
      no functional importance. Here we present an evaluation of an editing site in the
      ndhI/ ndhG intergenic region in a related group of monocot plants. Efficient
      editing of this site, as well as the phylogenetic conservation of the resulting
      uridine residue, point at an important role for the sequence restored by editing.
      Two potential functions can be envisaged. (1) RNA secondary structure predictions
      suggest that the C-to-U conversion at this site can lead to a modified stem/loop
      structure of the ndhG 5' UTR, which could influence ndhG expression. (2)
      Alternatively, editing of the ndhI/ ndhG intergenic region may tag a so far
      unidentified small (12-codon) ORF, and lead to the restoration of a conserved
      phenylalanine codon. A screen with specific antibodies elicited against the
      putative peptide failed to detect such a peptide in chloroplast fractions.
      However, this failure may be attributable to its low and/or development-specific
      expression.

PMID- 11976971
TI  - Ultrasound-guided thrombin injection of iatrogenic pseudoaneurysm at a community
      hospital.
AB  - The purpose of this study was to report the success rate of treating
      pseudoaneurysm using ultrasound-guided thrombin injection at a community
      hospital. Over 16-month period, 42 patients with femoral artery pseudoaneurysms
      were treated using ultrasound-guided thrombin injection. Our results showed that
      ultrasound-guided thrombin injection has a high success rate, and can be safely
      performed at a community hospital.

PMID- 11976972
TI  - Post-stroke and vascular depression: a critical review.
AB  - Increasing interest in depression within acute and chronic cerebrovascular
      pathology is justified for its clinical relevance. The scientific community
      strongly recommends taking into account its identification and management in
      efforts to reduce disability, the caregiver's burden and the social-economic
      impact of cerebrovascular disease. Different approaches observed in the
      literature review make it difficult to generalize about the evidence concerning
      crucial clinical issues such as diagnostic criteria, impact on functional
      improvement, selection or timing of depression treatment. Furthermore, the
      relationship between cerebral lesion location and depression is not agreed,
      because both hemispheres are reported as prevailing in published case series. On
      the other hand, vascular depression is commonly related to diffuse subcortical
      involvement. Because of its clinical and social impact, a definition of the
      unclear features of depression within acute and chronic cerebrovascular disease
      is urgently needed.

PMID- 11976973
TI  - The role of NCAM in remyelination.
AB  - The neural cell adhesion molecule (NCAM) is expressed by myelinating precursor
      cells in neonatal mouse spinal cord and by remyelinating cells after chemically
      induced demyelination in adult mouse. It shows tempting suggestions about its
      possible involvement in the reparative mechanisms and the remyelination processes
      that take place in multiple sclerosis (MS). In fact, its levels progressively
      increase in the cerebrospinal fluid (CSF) of acute MS patients subjected to
      steroid treatment, paralleling the progressive clinical improvement after the
      attack. Such an increase is not found in acute MS patients not treated with
      steroids nor in non-acute patients subjected to the same steroid treatment.

PMID- 11976974
TI  - Duplex scanning of neck vessels: need for extending the consensus on indications.
AB  - We studied the percentage and distribution of appropriate indications for duplex
      scanning of neck vessels in an outpatient population. A total of 650 consecutive
      outpatients sent by their general practitioner (GP) or a specialist for duplex
      scanning of epi-aortic arterial vessels were studied. The aim was to verify the
      percentage of appropriate (APR) an inappropriate (INAPR) indications for the
      examination, according to the current literature. After analysis of indications
      as reported by GPs or specialists and a brief anamnestic examination, 77% of
      patients were found to have had one or more APR and 23% of patients had none.
      Analysis of severity of atheromasic lesions between the two groups showed that
      patients with APR had significantly ( p<0.001, chi-square test) more severe
      lesions than patients with INAPR. In more detail, no patient with INAPR had
      severe (>60%) stenosis while 6.4% of patients with APR had severe stenosis.
      Moreover, the percentage of normal examinations or intima-media thickness only
      was 32.5% in patients with INAPR but fell to 17.2% in patients with APR. In the
      entire group, women were more represented than men even after consideration of
      the natural prevalence of female gender in the local population. Among
      inappropriate indications for the examination, isolated dizziness or vertigo,
      syncope and tinnitus were the most frequent. Continuous medical education is
      needed to reduce inappropriate indications and thus to find solutions, although
      partial, to shorten the waiting lists that have become an urgent problem for the
      public health systems of several Western countries. However, this appears to be
      difficult challenge, as experiments conducted on this issue by other researchers
      only gave transient positive results.

PMID- 11976975
TI  - Rey-Osterrieth complex figure: normative values in an Italian population sample.
AB  - The Rey-Osterrieth complex figure test (ROCF) is a neuropsychological test
      extensively used in clinical practice to investigate visuospatial constructional
      functions, visuographic memory and some aspects of planning and executive
      function. The aim of the present study was to collect normative values in an
      Italian normal population sample (n=280) for the direct copying and delayed (10
      min) reproduction of the ROCF. Multiple regression analysis revealed significant
      effects of age and education on performance of both copying tasks, whereas sex
      appeared to affect only performance on the delayed copying task. Inferential cut
      offs have been determined and equivalent scores computed. The availability of
      equivalent scores for the ROCF will prove useful in clinical assessment since it
      allows the comparison of a subject's performance on the ROCF with that on other
      neuropsychological tests for which normative values collected with similar
      methods are already available for the Italian population.

PMID- 11976976
TI  - Ischemic stroke subtypes: risk factors, functional outcome and recurrence.
AB  - The etiology of ischemic stroke affects its prognosis, outcome and management.
      Our aims were to determine risk factors, clinical and imaging variables and
      prognostic differences in acute ischemic stroke subtypes. In this study, we
      prospectively investigated 264 consecutive patients with acute ischemic stroke
      between 1996 and 2000. All of the patients were categorized to one of four major
      ischemic stroke subtype based on TOAST (Trial of Org 10172 in Acute Stroke
      Treatment) criteria. The mean age was greater in patients with stroke of
      undetermined etiology (SUE). Prevalence of hypertension was higher in patients
      with lacunar infarct (LAC) than other subtypes. Smoking was less frequent in
      patients with cardioembolism (CARD). The mean infarct size was largest in
      patients with large artery atherosclerosis (LAA) while there were no differences
      in location or conversion of the infarct into hemorrhage. The proportion of the
      patients with milder neurological deficits at entry was higher in patients with
      LAC subtype. The rate of independent patients were different between subtypes:
      62% in LAC, 43% in CARD, 38% in SUE, 35% in LAA at discharge ( p=0.01), and 91%
      in LAC, 69% in CARD, 59% in SUE, 60% in LAA at 6 months ( p<0.001). Recurrence
      rates were not different between groups. We conclude that risk factors, clinical
      imaging variables are different among ischemic stroke subtypes and that
      neurological status on admission and during follow-up strongly favors LAC.

PMID- 11976978
TI  - P300 and executive function alterations: possible links in a case of Morgagni
      Stewart-Morel syndrome.
AB  - To evaluate possible cause-effect relationships between hyperostosis frontalis
      interna and cognitive dysfunction, we performed a neurophysiological (event
      related potentials, ERPs) and neuropsychological study in a case of Morgagni
      Stewart-Morel (MSM) syndrome associated with frontal lobe compression.
      Neuropsychological evaluation evidenced selective impairment of executive
      function. Visual and auditory oddball ERPs revealed delayed P300 latency and
      reduced auditory P300 amplitude with multi-peaked morphology. ERP abnormalities
      and cognitive dysfunction could be due to the frontal bone-cortex conflict
      documented by neuroradiological investigations.

PMID- 11976977
TI  - Occurrence of factor V Leiden mutation (Arg506Gln) and anticardiolipin antibodies
      in migraine patients.
AB  - The occurrences of factor V Leiden mutation (Arg506Gln) and antiphospholipid
      antibodies (APA) in migraine patients have been reported, but the findings are
      controversial. We investigated the presence of factor V Leiden and the serum
      level of anticardiolipin antibodies (aCL) in a consecutive series of 70 migraine
      patients (47 women; mean age, 34.1 years). Of these, 40 patients had migraine
      with aura. A matched sample of 70 healthy people was considered as the control
      group. Heterozygous genotype for factor V Leiden mutation was detected in 4
      (5.7%) migraine patients (of which 2 had migraine with aura) and in 2 (2.8%)
      subjects of the control group. Although proportionally more migraine patients
      harbored the factor V Leiden mutation, this difference was not statistically
      significant, perhaps due to the small number of patients involved. We found
      normal serum levels of aCL in all migraine patients. Further studies and a long
      term follow-up are warranted to determine the significance of this genetic
      abnormality in migraine.

PMID- 11976979
TI  - Atypical tentorial meningioma 30 years after radiotherapy for a pituitary
      adenoma.
AB  - Although the human central nervous system used to be considered relatively
      resistant to the carcinogenic action of ionizing radiation, several lines of
      evidence now document a high incidence of secondary tumors in irradiated
      patients. The numerous reports of radiation-induced cerebral meningiomas
      generally distinguish those induced by high-dose radiation from those induced by
      low-dose radiation. We describe the case of patient who underwent subtotal
      resection of a chromophobe pituitary adenoma at the age of 18 years, who was
      successively treated by conventional fractionated radiotherapy with gamma rays
      emitted by a source of 60Co until a total dose of 41 Gy. Over the next 30 years
      the patient experienced all the known late effects of radiation, including
      panhypopituitarism, cranial-nerve deficits (II, III and VI), massive radiation
      necrosis involving the left cerebral hemisphere and causing right hemiparesis and
      aphasia and, ultimately, an atypical tentorial meningioma with early recurrence
      after total resection.

PMID- 11976980
TI  - Cardiac papillary fibroelastoma: an unusual source of cerebral embolism solved
      with local fibrinolysis.
AB  - Fibroelastoma is an infrequent tumor affecting mainly cardiac valves. Before
      echocardiography, it was an occasional autoptic finding. With the development of
      ultrasonographic techniques, it is currently possible to carry out diagnosis in
      vivo. We report the case of a young woman with cerebral ischemia who was
      successfully treated by intra-arterial fibrinolysis with complete clinical
      resolution. Transesophageal echocardiography (TEE) identified a papillary
      fibroelastoma on the posterior leaflet of the mitral valve. Surgical excision of
      the tumor was performed. Sudden cerebral or peripheral embolization is frequently
      linked to thrombotic material which surrounds the neoplasm, and thus can be
      successfully treated with local fibrinolysis.

PMID- 11976981
TI  - Brain-derived neurotrophic factor is not altered in the serum and cerebrospinal
      fluid of amyotrophic lateral sclerosis patients.

PMID- 11976982
TI  - Phototherapy of psoriasis: update with practical pearls.

PMID- 11976985
TI  - Pathophysiology of psoriasis: science behind therapy.

PMID- 11976984
TI  - Topical agents for the treatment of psoriasis, past, present and future.

PMID- 11976986
TI  - Pediatric psoriasis revisited.

PMID- 11976987
TI  - Drug interactions in psoriasis: the pros and cons of combining topical psoriasis
      therapies.

PMID- 11976988
TI  - Management of chronic viral hepatitis in HIV-infected patients: Spanish Consensus
      Conference. October 2000.
AB  - Co-infection by human immunodeficiency virus and hepatitis B and C viruses is
      quite common because they share similar routes of transmission. The introduction
      of highly active antiretroviral therapy has significantly improved the life
      expectancy of HIV-infected patients in the last few years. However, chronic viral
      hepatitis represents an emerging cause of morbidity and mortality in this
      population, either as a result of end-stage liver disease or as a consequence of
      hepatotoxicity induced by antiretroviral drugs. The main goal of the Consensus
      Conference was to establish specific recommendations for the management of
      chronic viral hepatitis B and C in HIV-infected patients. The role of orthotopic
      liver transplantation for co-infected individuals with end-stage liver disease
      was also assessed.

PMID- 11976989
TI  - Control of HIV during a structured treatment interruption in chronically infected
      individuals with vigorous T cell responses.
AB  - PURPOSE: To study whether and under what circumstances HIV can be controlled in
      chronically infected patients. METHOD: Nine patients treated with hydroxyurea and
      didanosine (PANDAs) were compared with 7 patients on highly active antiretroviral
      therapy (HAART) during an 8-week treatment interruption. Both groups had similar
      baseline viral load, CD4 count, and length of treatment. Treatment was resumed if
      viral rebound >10,000 copies/mL (virological failure) or CD4 count decrease below
      200 cells/mm(3) (immunological failure) occurred in two consecutive measurements.
      RESULTS: None of the PANDAs failed. Viral rebound was spontaneously contained,
      and CD4 count remained stable. Four out of 7 patients in the HAART group failed
      to control HIV by week 6 and had to restart therapy due to either viremia rebound
      or CD4 decrease. Before therapy interruption, the PANDAs had a vigorous HIV
      specific T cell immune response (median CD4VIR 1.2%), while the HAART-treated
      patients did not (median CD4VIR 0.2%) (CD4VIR represents the percentage of HIV
      specific CD4 subpopulation expressing IFN-gamma within the total CD4 population
      [CD3+, CD4+, IFN-gamma+]). This difference was statistically significant (p
      =.002). CONCLUSION: This study shows that HIV can be controlled during therapy
      interruption in patients with established infection, and that control of viral
      replication correlates with vigorous anti-HIV specific immune responses.

PMID- 11976992
TI  - Differential characteristics of HIV-infected penitentiary patients and HIV
      infected community patients.
AB  - PURPOSE: To identify particular characteristics of HIV+ patients from
      correctional facilities (CF) compared with an HIV+ population from the community
      to better detect variables for intervention. METHOD: In our hospital, HIV+
      patients are admitted to an infectious diseases ward (IDW) when they come from
      the community or to a penitentiary unit (PU) when they are transferred from CF.
      We retrospectively reviewed admissions of those patients in both areas during
      1999. RESULTS: Admissions of HIV+ patients to IDW and PU generate 2.3% and 53.4%
      of hospital and PU stays, respectively. Both populations were equivalent in terms
      of mean age, CD4 count, viral load, prophylaxis for opportunistic infections,
      average stay, and death during stay. Male sex (91% vs. 74%), previous or current
      intravenous drug use (88% vs. 77%), and hepatitis C virus (HCV) seropositivity
      (97% vs. 82.6%) were more frequent in the PU than in the IDW. Multivariate
      analysis identified three factors as being independently related to admission
      from prison: longer time of known HIV infection (average 3.3 years; 95% CI 1.9
      4.6), no previous antiretroviral treatment (odds ratio [OR] 2.95; 95% CI 1.46
      6.0), and admission due to tuberculosis (OR 2.5; 95% CI 1.03-6.0). CONCLUSION:
      HIV infection is still a serious medical problem in CF. Although imprisonment can
      provide access to health programs, HIV-infected prison patients suffer more
      frequently from tuberculosis and take less antiretroviral treatment.

PMID- 11976991
TI  - Serum prolactin concentrations in patients infected with human immunodeficiency
      virus.
AB  - PURPOSE: To analyze the prevalence, effects of HAART, and implications of
      hyperprolactinemia in HIV-infected patients. METHOD: 192 HIV-infected men in
      stable clinical condition who underwent 355 measurements of prolactin were
      prospectively studied. Other clinical, immunologic, virologic, and laboratory
      parameters were also evaluated at the time of each prolactin measurement.
      RESULTS: Hyperprolactinemia was observed in 21.4% of the patients.
      Hyperprolactinemia was more commonly found in patients receiving opioids than in
      those who were not (p =.03), but it was not influenced by a past diagnosis of
      AIDS, presence of metabolic disturbances, gynecomastia, or viral load. Patients
      noninfected with hepatotropic viruses had slightly higher prolactin levels than
      those who were infected (p =.049). There were significant differences in the
      rates of hyperprolactinemia according to different CD4 strata, with higher rates
      in patients with higher CD4 counts. Similarly, hyperprolactinemic patients had
      higher CD4 counts than patients with normal prolactin (p =.038). Antiretroviral
      therapy was not associated with prolactin levels. CONCLUSION: Hyperprolactinemia
      is a common finding in HIV infection and is observed in about one fifth of male
      patients in stable clinical condition. It is not related to antiretroviral
      therapy, metabolic disturbances, liver disease, or viral load. The implications
      of its association with CD4 counts are unclear and should be investigated.

PMID- 11976990
TI  - Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily
      pretreated patients.
AB  - OBJECTIVE: To evaluate the safety profile and efficacy of salvage regimens
      containing amprenavir (APV) 600 mg twice daily and ritonavir (RTV) 200 mg twice
      daily. DESIGN: Prospective, single-center study. METHOD: The patient database of
      the department of infectious diseases was screened for patients who had failed at
      least two successive three-drug combinations. These patients were proposed to
      take APV and RTV in association with two to four other drugs. They were followed
      monthly for 6 months. RESULTS: Seventeen patients were included. They had been
      previously treated for 70 +/- 23 months. At baseline, viral load (VL) was 4.86 +/
      0.98 log10 copies/mL and CD4 187 +/- 145 10(6)/L. On week 24, using intent-to
      treat analysis, VL decreased to 2.95 +/- 1.59 log10 copies/mL and CD4 increased
      to 365 +/- 210 10(6)/L. Nine patients (53%) had a VL < 2.3 log10 copies/mL. The
      most common adverse events were grade 1 or 2 diarrhea and an increase of
      cholesterol and triglyceride levels. Mean APV trough concentration was 1727 +/-
      1749 ng/mL on week 24. CONCLUSION: These data show that the combination of low
      dose RTV and reduced doses of APV is safe. This combination can be added to
      nonnucleoside analogs.

PMID- 11976993
TI  - Clinical signs and symptoms in the assessment of immunodeficiency in men with
      subtype C HIV infection in Harare, Zimbabwe.
AB  - PURPOSE: Providing low-cost interventions such as co-trimoxazole as prophylaxis
      against opportunistic infections among HIV-infected individuals depends on the
      identification of those at risk. This article describes the prevalence of self
      reported signs and symptoms and CD4 cell counts in a cohort of 447 HIV
      seropositive men. A scoring system using self-reported signs and symptoms was
      developed and tested in the prediction of low CD4 cell counts. This approach may
      allow health care providers in low-resource settings to predict severe
      immunodeficiency and to provide care. METHOD: Data on clinical manifestations of
      HIV infection and blood samples for HIV serology were collected prospectively
      from an ambulatory cohort of men seen at their workplace at enrollment and every
      6 months thereafter. CD4+ cell counts were obtained on samples testing positive
      on ELISA. Using data reduction techniques and logistic modeling, we developed a
      prognostic score system. RESULTS: 20% of the men had CD4+ cell counts below 200.
      All reported signs and symptoms were more frequent in men with less than 200 CD4+
      cell counts compared to men with CD4+ cell counts greater than 200. History of
      malaria, fever, lymphadenopathy, persistent diarrhea, persistent cough, and skin
      infections robustly predicted low CD4+ count. A scoring system equation was
      developed based on the coefficients of the multivariate logistic regression:
      1x(tuberculosis) + 3.2x(herpes zoster) + 4.5x(malaria) + 5.7x(fever) +
      5.8x(cough) + 8.2x(lymphadenopathy) + 8.5x(skin infection). Setting the score
      cutoff value greater than or equal 5, the model had moderately high sensitivity
      of 61% and specificity of 72%. The scoring system had an overall classification
      error rate of 30%. CONCLUSION: By using this simple scoring system, physicians
      can correctly identify 72% of patients who do not require immediate intervention,
      thereby channeling scarce resources to those who have both low CD4+ cell counts
      and symptoms and are most likely to benefit from prophylactic and antiretroviral
      interventions.

PMID- 11976994
TI  - Increasing prevalence of resistance mutations in antiretroviral-naive individuals
      with established HIV-1 infection from 1996-2001 in St. Louis.
AB  - BACKGROUND: Transmission of drug-resistant virus in HIV-1 infected individuals is
      well documented, particularly in patients with primary infection. Prevalence in
      chronically infected antiretroviral-naive patients is reportedly low. Routine
      genotyping in this population is not recommended. PURPOSE: The purpose of this
      study was to evaluate resistance profiles in patients with established HIV
      infection in St. Louis. METHOD: We selected specimens from drug-naive individuals
      (CD4 >300 cells/mL and VL >1000 copies/mL) with established HIV infection between
      1996-2001. 62 of 75 specimens were available for genotyping. We excluded patients
      with evidence of acute HIV infection and long-term nonprogressors. RESULTS: The
      overall prevalence of resistance was 11% (7/62). From 1996 to 1998, a prevalence
      of 4% was observed (1/27 individuals). During the subsequent period from 1999 to
      2001, the frequency increased to 17% (6/35 participants; p =.08; 95% CI 5-29%).
      CONCLUSION: The results suggest that the prevalence of primary resistance is
      increasing in our region to the point that it justifies genotypic testing in all
      individuals before the initiation of antiretroviral therapy. This has to be
      considered when designing antiretroviral clinical trials.

PMID- 11976995
TI  - Frequency of medical history items, drug interactions, and lifestyle
      characteristics that may interfere with antiretroviral medications.
AB  - PURPOSE: There were two study questions: How often do HIV-infected patients
      present with a medical history or concurrent medication use that might
      contraindicate the use of one or more antiretroviral drugs? What is the frequency
      of patients having lifestyle behaviors that might preclude them from successfully
      following an antiretroviral drug regimen? METHOD: One hundred patients were given
      a 52-item questionnaire that asked about their medical histories, concurrent use
      of non-HAART drugs, and lifestyle. The results were analyzed to determine the
      frequency of potential side effects, drug interactions, or lifestyle behaviors
      that could interfere with the patient being able to successfully adhere to
      antiretroviral drug regimens. RESULTS: 96% of the patients had at least one
      medical history item or were taking at least one medication that could
      potentially create a serious side effect to one or more of the 14 antiretroviral
      drugs that were studied. All of the patients had at least one lifestyle behavior
      that would have interfered with successful adherence to one or more of the drugs.
      CONCLUSION: The questionnaire utilized in the study identified potential factors
      that could cause medical problems or that could interfere with the successful use
      of various antiretroviral drugs. The frequency of occurrence of these factors was
      unexpectedly high.

PMID- 11976996
TI  - Assessment of readiness to initiate antiretroviral therapy.
AB  - PURPOSE: An important factor in adherence to antiretroviral therapy (ART) is the
      patient's commitment to follow the regimen, which suggests that therapy should be
      initiated only when the patient is ready to make such a commitment. Because there
      has been no research on patient readiness for ART, this study was undertaken to
      investigate factors that influence the decision of an HIV-positive person to seek
      medical care and to initiate ART. METHOD: The investigators surveyed 83 HIV
      infected patients on ART. Participants completed a questionnaire that obtained
      information on the length of time from when they learned of their HIV-positive
      status to when they sought medical care, the length of time from when they
      learned of their HIV-positive status to when they were ready to initiate therapy,
      and psychological and social factors thought to be associated with readiness.
      RESULTS: Respondents had a mean age of 37 years, 71% were male, and 65% were
      African American. Only 42% said they sought medical care immediately upon
      learning their HIV diagnosis. Fifty percent were ready to initiate therapy
      immediately upon learning their diagnosis, and 25% were ready within 1 year.
      Sixty-four percent of respondents experienced barriers that interfered with
      therapy initiation. Although 98% of respondents experienced at least one
      emotional response to HIV diagnosis, less than 25% of respondents thought that
      their responses interfered with readiness. However, five emotional responses
      demonstrated an association with readiness through chi-square analysis.
      CONCLUSION: Further research is needed to explain the relationships among
      emotional responses to HIV diagnosis, readiness to initiate ART, and adherence.

PMID- 11976997
TI  - Continuing debate over HIV therapy initiation.
AB  - Initiation of highly active antiretroviral therapy (HAART) in human
      immunodeficiency virus (HIV) infection has changed the landscape of HIV/AIDS
      care. However, the potential for long-term complications from therapy has
      emerged, and the risk/benefit associated with usage now merits more extensive
      evaluation. As data from ongoing and future clinical trials continue to
      accumulate, individualization of therapy may be the appropriate option for HIV
      infected individuals.

PMID- 11976998
TI  - The manuscript review process.

PMID- 11976999
TI  - Partnership for the advancement of clinical informatics.

PMID- 11977000
TI  - Nurses and nursing in the health care quality policy arena.

PMID- 11977001
TI  - Nursing science defined in less than 10 words.

PMID- 11977002
TI  - The nursing shortage is a symptom.

PMID- 11977003
TI  - Penn Macy initiative to advance academic nursing practice.
AB  - Academic nursing practice holds great promise for the future of the nursing
      discipline. The successful and intentional integration of the tripartite mission
      of research, education, and clinical practice can facilitate both the evolution
      of the science and implementation of evidence-based practice, while imbuing
      practitioners in the making with the world of the possible. Although many schools
      of nursing have been involved in some aspects of academic practice, the lack of
      common focus and direction has hampered concerted movement. The Penn Macy
      Initiative was conceived as a vehicle to help build and coalesce the critical
      mass needed to bridge this gap. The Penn Macy Initiative, its implementation and
      experience in the first 3 years, and how its alumni fellows, an annual
      conference, and Web-based consultation will continue to provide impetus,
      leadership, and resources for academic nursing practice in the years to come are
      described.

PMID- 11977004
TI  - Opportunities in preparing global leaders in nursing.
AB  - During the past decade, there has been a large increase in the number of
      international nurses pursuing doctoral education in the United States. The influx
      of these nurses has ramifications for the institutional systems providing
      education as well as on international and American nursing students. To begin
      understanding the issues presented by international doctoral nursing education, a
      survey of U.S. schools of nursing as well as a focus group of currently enrolled
      international doctoral students was conducted. The survey revealed that both
      international students and nursing programs experience challenges with regard to
      language, communication, financing, and support systems. More specifically,
      information gathered from the focus group identified issues regarding (1) lack of
      familiarity with the U.S. health care system, (2) lack of previous experience
      with the seminar format used in doctoral programs, (3) restricted opportunities
      to participate in faculty research, and (4) stress from a heavy course load to
      finish the program within a very short time period. Universally, the surveys and
      focus group lauded the positive global perspective imbued on all students and
      faculties via the international connection. Nonetheless, schools of nursing need
      to identify more effective strategies to aid international students in their
      development as successful global leaders. Meleis's framework for culturally
      competent scholarship is offered as a guide for schools of nursing.

PMID- 11977005
TI  - Transition to community-based nursing curriculum: processes and outcomes.
AB  - As the health care delivery system evolves, nurse educators must prepare
      graduates who can meet the comprehensive health needs of communities in a variety
      of settings. This article describes one college's process of curricular change
      from a traditional to community-based format. The concepts that guided curriculum
      development and implementation are presented, along with the outcomes that have
      resulted from this change. Lessons learned as the curriculum was restructured are
      described.

PMID- 11977006
TI  - Community of Communities: an electronic link to integrating cultural diversity in
      nursing curriculum.
AB  - The inclusion of principles of diversity in nursing education has yet to reach
      expected levels of common understanding and value. Integration of human diversity
      is an expected outcome based on essentials for professional nursing education by
      the American Association of Colleges of Nursing. This article describes one
      approach that used electronic networking to integrate cultural diversity content
      into a graduate nursing curriculum. Regional networking among schools of nursing
      about cultural diversity resulted in the Community of Communities (COC) web page.
      The COC is a common electronic network that contains information and case studies
      based on a cultural assessment model. Modules in on-line courses are linked to a
      cultural module in the COC. Several applications are described herein. The COC
      modules were evaluated to determine if participants gained knowledge and insight
      into another culture. Findings suggested that students perceived that the COC
      modules increased the awareness culture plays in health care.

PMID- 11977007
TI  - Developing an instrument to measure and describe clinical decision making in
      different nursing fields.
AB  - The purpose of this study was to develop and test a decision-making instrument
      for nursing, to consider the nursing decision-making models in different nursing
      fields, and to create a scoring system for the instrument. A 56-item instrument
      was developed on the basis of different decision-making theories and earlier
      studies about nursing decision making. The instrument was evaluated by using
      several different convenience samples of nurses from seven different countries (N
      = 1,460). Statistical analysis used were correlation coefficients, factor
      analysis, factor scores, and factor reliability coefficients. The results
      indicated that nurses from different countries and working in different fields of
      nursing respond similarly. The results of the studies using the 56-item
      instrument showed that nurses use four kinds of decision-making models
      (analytical, analytical-intuitive, intuitive-analytical, and intuitive). The
      factor reliability scores were high (alpha = 0.85-0.91). According to the
      results, 60 per cent of the nurses used the analytical-intuitive and intuitive
      analytical decision-making models, 14 per cent used the analytical model, and 26
      per cent used the intuitive model. However, these models vary both between and
      within different fields of nursing.

PMID- 11977008
TI  - The health-promoting lifestyles of undergraduate nurses in Hong Kong.
AB  - Based on Pender's health promotion model in 1987, this descriptive study of 169
      undergraduate nurses in Hong Kong was undertaken to determine any differences in
      their health-promoting lifestyles, as measured by the Health Promoting Lifestyle
      Profile II (HPLP II) among different age groups, gender, income, employment
      status, and levels in undergraduate nursing education. The student nurses
      performed best in interpersonal relations but worst in physical activity. There
      were significant differences among the various classes in stress management and
      spiritual growth, with senior classes (Years 3 and 4) reporting worse in both
      areas. This was particularly remarkable among the students of the final year, who
      would soon be graduating as staff nurses and were expected to inspire patients to
      practice health-promotive behaviors by their example. The older age group also
      had lower scores in stress management and exercise practice. Because most of the
      students in the senior classes were older, the findings further reinforce the
      earlier results. It was also identified that more than half of the students were
      supported on low parental income with many of them working a part-time job. These
      outcomes were explored with future recommendations made to improve the weaknesses
      in the students' health-promoting lifestyles.

PMID- 11977011
TI  - Surgical techniques for pulmonary metastasectomy.
AB  - The surgical approaches to pulmonary metastasectomy have evolved during the past
      20 years. Important principles include the complete resection of all gross
      disease, the use of parenchyma-sparing resections, and the simultaneous resection
      of bilateral metastases wherever technically feasible. Video-assisted thoracic
      surgery resection has become popular, but is still not standard because it can
      lead to an incomplete resection. Stapled and precision electrocautery wedge
      resections remain the most common techniques for parenchymal resection.

PMID- 11977012
TI  - Biology of metastatic disease.
AB  - Metastasis development is a complex series of events involving the generation of
      new blood vessels, growth, invasion with breakdown of the host matrix, transport
      to other sites with adhesion, and subsequent invasion of the organ that hosts the
      metastasis. It is only recently that the molecular basis for these events has
      been studied, and the understanding of this process is now leading to the
      development of therapies that targets one or more of the components of this
      series of events.

PMID- 11977013
TI  - History of the surgical management of pulmonary metastases and development of the
      International Registry.
AB  - Pulmonary metastasectomy has been gradually recognized as a potentially curative
      treatment in properly selected cases, and a greater number of patients are now
      being offered salvage surgery. The results of the International Registry of Lung
      Metastases (IRLM) have defined the long-term survival after metastasectomy and
      provided a new classification system combining anatomical and biological features
      to assess prognosis in the various primary tumors.

PMID- 11977014
TI  - Resection of pulmonary metastases from colorectal cancer.
AB  - Colorectal cancer is one of the most prevalent malignancies in the United States.
      It has a well-recognized tendency to metastasize to the lungs, and under certain
      circumstances, these metastases are resectable. Data accumulated over the last 40
      years support a survival benefit from resection of these lesions and have given a
      better understanding of the indications that should be adhered to in performing
      metastasectomy for colorectal cancer.

PMID- 11977015
TI  - The role of pulmonary metastasectomy in soft tissue sarcoma.
AB  - Pulmonary metastases are common in patients with soft tissue sarcoma. The
      majority of patients who develop pulmonary metastases are asymptomatic and are
      diagnosed during routine follow-up visits. There is evidence to suggest that
      pulmonary metastasectomy is associated with improved overall survival but only in
      patients with complete surgical resection. There are several criterion to
      identify patients for resection. The majority of resectable patients have
      peripheral lesions that are amenable to wedge resection. There is little evidence
      to suggest that chemotherapy improves survival. Future research is needed to
      better identify patients for metastasectomy, to determine the role of minimally
      invasive procedures, and to develop better adjuvant therapy.

PMID- 11977016
TI  - Pulmonary metastasectomy for metastatic malignant melanoma.
AB  - Melanoma is the most deadly of skin cancers, and metastatic disease most commonly
      first appears in the lungs. Because most patients with early metastatic pulmonary
      disease are asymptomatic, routine screening with chest radiographs is the most
      cost-effective method of discovery. The therapy for pulmonary metastatic melanoma
      has drastically changed over the years. Even today there is no curative
      immunotherapy or chemotherapy available. The long-term overall survival for these
      patients is still very poor, but early detection and surgery offers the only hope
      for control in a small number of patients.

PMID- 11977017
TI  - New and evolving treatment methods for pulmonary metastases.
AB  - Treatment strategies other than surgery for pulmonary metastases are needed to
      improve disease-free and overall survival. Surgical attempts to solve a biologic
      problem by mechanical means. Alternative treatment may include induction or
      adjuvant chemotherapy, lung perfusion or regional drug delivery, biologic
      therapies (inhaled IL-2, biologic modifiers), and potentially, molecular or
      genetic therapy. Experimental radiofrequency ablation techniques are rarely
      applicable. Combinations of resection of macrometastases with treatment of occult
      micrometastases may be best in improving disease-free and overall survival.

PMID- 11977019
TI  - Limited-access surgical coronary artery revascularization.
AB  - The continued evolution of surgical revascularization has resulted in much less
      invasive alternatives for patients undergoing coronary artery bypass grafting. In
      particular, techniques and technologies have been developed to allow for the
      grafting of coronary arteries through limited access incisions without the
      circulatory support of cardiopulmonary bypass. The conduits are generally
      arterial rather than the venous alternatives used originally, and the harvesting
      of these conduits is performed through limited access incisions described in
      another article in this review. The result of these efforts is sternal-sparing
      solutions for the off-pump coronary artery bypass grafting of all the various
      coronary locations on the heart. This is accomplished through a spectrum of small
      incisions that can directly expose any specific area of interest for focal bypass
      grafting. The surgical insult is greatly reduced and the patient's recovery is
      significantly enhanced. These efforts continue to bring us closer to the ultimate
      goal of 24-hour hospital stays for coronary artery bypass grafting patients.

PMID- 11977020
TI  - Off-pump coronary revascularization: current state of the art.
AB  - Patients presenting for surgical coronary artery bypass grafting (CABG) are older
      and have more comorbidity than patients in prior decades. Cardiopulmonary bypass
      (CPB) may add to the elevated morbidity and mortality seen in these higher-risk
      patients. After the re-introduction of single-vessel bypass without CPB, surgeons
      have developed techniques for multivessel off-pump coronary artery bypass (OPCAB)
      through sternotomy. Understanding the causes of the hemodynamic disturbances seen
      during cardiac displacement has led to surgical techniques that minimize
      mechanical compression and the effects of temporary regional ischemia. With
      careful attention to detail, OPCAB has been shown to be feasible in nearly all
      patients needing coronary artery bypass. The procedure has been demonstrated to
      be safe and effective. Early outcomes and graft patency rates appear to be at
      least as good as those seen with traditional CPB-supported CABG. Certain high
      risk groups may be better treated with OPCAB, but further studies are necessary
      to elucidate which patients should be offered OPCAB and which should receive
      standard CABG.

PMID- 11977021
TI  - Recent progress in minimally invasive conduit harvesting.
AB  - Wound-related morbidity frequently encountered after open-incision harvesting of
      vessel conduits for coronary artery bypass grafting (CABG) is invariably
      recognized as an obstacle impeding the patient's path towards complete
      postoperative recovery. The endoscopic approach provides surgical access to the
      intended conduit vessel while affording an appreciably lower incidence of
      traumatic injury to the surrounding tissues. For this reason, the minimally
      invasive endoscopic dissection of vessel conduits is steadily gaining acceptance
      as a preferable alternative to the standard open-incision technique. Endoscopic
      systems, originally developed for general surgical procedures in the early 1990s,
      and readily adapted to saphenous vein harvesting by mid-decade, are now also
      being applied to minimally invasive radial artery harvesting. The growth of this
      surgical modality has paralleled the rapid development of remote access minimally
      invasive endoscopic devices and technologies and therefore remains an evolving
      body of knowledge. As experience and refinements in instrumentation progress, the
      endoscopic approach will undoubtedly become the procedure of choice for
      harvesting vessel conduits. This article provides a practical primer, based on
      the benefit of our serial experience with endoscopic vein and radial artery
      dissections, for those considering the minimally invasive endoscopic approach in
      harvesting vessels for CABG.

PMID- 11977023
TI  - Current status and future directions in computer-enhanced video- and robotic
      assisted coronary bypass surgery.
AB  - Since 1997, both the Cleveland Clinic and London Health Sciences Centre groups
      have embraced robotic assistance and more recently demonstrated the efficacy of
      this technology in totally closed-chest, beating heart myocardial
      revascularization. This endeavor involved an orderly progression and the learning
      of new surgical skill sets. We review the evolution of robot-enhanced coronary
      surgery and forecast the future of endoscopic and computer-enhanced, robotic
      enabling technology for coronary revascularization. This report describes a
      computer-assisted totally closed-chest coronary bypass operation, and preliminary
      results are discussed. The internal thoracic artery (ITA) was harvested through
      three 5-mm access ports and prepared and controlled endoscopically. A prototype
      sternal elevator was used to increase intrathoracic working space. A 10-mm
      endoscopic stabilizer was placed through the second intercostal space, and the
      left anterior descending coronary artery was controlled with silastic snares.
      Telerobotic anastomoses were completed end-to-side using custom-made, double
      armed 8-0 polytetrafluroethylene sutures. To date, 84 patients have undergone
      successful myocardial revascularization with robotic assistance with a 0%
      surgical mortality rate. ITA harvest, anastomotic, and operating times for the
      entire group have been longer than for conventional surgery at 61.3 +/- 17.9
      minutes, 28.5 +/- 28.2 minutes, and 368 +/- 129 minutes, respectively. Bleeding,
      ventilatory times, arrhythmias, hospital lengths of stay, and return to normal
      activity have been reduced. Recently, we have developed a new robotic
      revascularization strategy called Atraumatic Coronary Artery Bypass that is a
      promising mid-term step on the pathway to totally endoscopic, beating-heart
      coronary artery bypass. We conclude that computer-enhanced robotic techniques are
      safe, and further clinical studies are required to define the full potential of
      this evolving technology.

PMID- 11977022
TI  - Facilitated vascular anastomosis in coronary bypass surgery.
AB  - The goal of truly minimally invasive surgical revascularization with 1-day
      hospital stays is shared by surgeons, patients, and payors alike. However,
      accomplishing this will involve doing surgery through more limited-access
      incisions and working within closed spaces. Suture management in this setting is
      cumbersome, slow, and unreliable. Facilitated anastomotic techniques and
      technologies are generally believed to be the vehicle that will ultimately allow
      us to address this. A considerable amount of time and resources has already been
      expended by many people and companies in this effort, with early clinical
      progress now being reported. Much more remains to be done, and other new
      approaches still need to be investigated. This article provides an overview or
      snapshot of the work and progress to date with facilitated vascular anastomoses
      along with some of the challenges that have yet to be solved. The achievement of
      a predictable, reproducible, and reliable technique to accomplish this will
      significantly and irrevocably reduce the extent of surgery required to
      revascularize the heart.

PMID- 11977024
TI  - Alternatives to traditional coronary bypass surgery.
AB  - Over 1 million percutaneous coronary interventions (PCI) and a half million
      surgical coronary artery bypass grafting procedures (CABG) are performed in the
      United States annually for treatment of coronary artery disease. With recent
      advances in anti-restenosis strategies, the number of PCIs is expected to
      increase dramatically. Still, these therapies treat relatively discrete coronary
      lesions. However, there is a relatively large number of patients for whom
      traditional therapies are not optimal, either because there are diffuse coronary
      artery lesions, because there are chronic total occlusions, or because, in the
      instance of bypass surgery, creating proximal or distal anastomoses is
      problematic. We review three strategies in various stages of development aimed at
      treating patients not optimally served by traditional forms of revascularization:
      transmyocardial laser revascularization, angiogenic therapies, and direct
      ventricle-to-coronary artery bypass.

PMID- 11977078
TI  - A healthy understanding of intraflagellar transport.
AB  - A microtubule-dependent motility process called intraflagellar transport (IFT)
      occurs beneath the plasma membrane of cilia and flagella. IFT was first observed
      in Chlamydomonas, and orthologs of some of the polypeptides involved in IFT have
      recently been identified in other organisms, including C. elegans and the mouse.
      In addition to a role in the assembly and maintenance of cilia and flagella,
      evidence is reviewed here that indicates defects in the process of IFT may be
      related to problems with human health. Moreover, recent data suggest the
      possibility of two new roles for IFT in cell function. The first is in
      transcriptional control of the genes encoding ciliary and flagellar proteins. IFT
      could provide a mechanism whereby the cell senses the presence or absence of its
      cilia or flagella and responds by turning on gene transcription resulting in
      replacement of the missing organelle. The second role is in signal transduction,
      whereby cilia act as sensors of the external cellular environment and transduce
      information about the surroundings into intracellular signals that are sent via
      IFT to the cell body, thus inducing an appropriate cellular response to the
      environment.

PMID- 11977079
TI  - Villin-type headpiece domains show a wide range of F-actin-binding affinities.
AB  - The villin-type "headpiece" domain is a modular motif found at the extreme C
      terminus of larger "core" domains in over 25 cytoskeletal proteins in plants and
      animals. Although headpiece is classified as an F-actin-binding domain, it has
      been suggested that some expressed fusion-proteins containing headpiece may lack
      F-actin-binding in vivo. To determine the intrinsic F-actin affinity of headpiece
      domains, we quantified the F-actin affinity of seven headpiece domains and three
      N-terminal truncations, under identical in vitro conditions. The constructs are
      folded and adopt the native headpiece structure. However, they show a wide range
      of affinities that can be grouped into high, low, and nonspecific-binding
      categories. Computer models of the structure and charged surface potential of
      these headpiece domains suggest features important for high F-actin affinity. We
      conclude that not all headpiece domains are intrinsically F-actin-binding motifs,
      and suggest that the surface charge distribution may be an important element for
      F-actin recognition.

PMID- 11977080
TI  - Plant profilin isovariants are distinctly regulated in vegetative and
      reproductive tissues.
AB  - Profilin is a low-molecular weight, actin monomer-binding protein that regulates
      the organization of actin cytoskeleton in eukaryotes, including higher plants.
      Unlike the simple human or yeast systems, the model plant Arabidopsis has an
      ancient and highly divergent multi-gene family encoding five distinct profilin
      isovariants. Here we compare and characterize the regulation of these profilins
      in different organs and during microspore development using isovariant-specific
      monoclonal antibodies. We show that PRF1, PRF2, and PRF3 are constitutive, being
      strongly expressed in all vegetative tissues at various stages of development.
      These profilin isovariants are also predominant in ovules and microspores at the
      early stages of microsporogenesis. In contrast, PRF4 and PRF5 are late pollen
      specific and are not detectable in other cell types of the plant body including
      microspores and root hairs. Immunocytochemical studies at the subcellular level
      reveal that both the constitutive and pollen-specific profilins are abundant in
      the cytoplasm. In vegetative cell types, such as root apical cells, profilins
      showed localization to nuclei in addition to the cytoplasmic staining. The
      functional diversity of profilin isovariants is discussed in light of their
      spatio-temporal regulation during vegetative development, pollen maturation, and
      pollen tube growth.

PMID- 11977081
TI  - Regulation of flagellar dynein by the axonemal central apparatus.
AB  - Numerous studies indicate that the central apparatus, radial spokes, and dynein
      regulatory complex form a signaling pathway that regulates dynein activity in
      eukaryotic flagella. This regulation involves the action of several kinases and
      phosphatases anchored to the axoneme. To further investigate the role of the
      central apparatus in this signaling pathway, we have taken advantage of a
      microtubule-sliding assay to assess dynein activity in central apparatus
      defective mutants of Chlamydomonas. Axonemes isolated from both pf18 and pf15
      (lacking the entire central apparatus) and from pf16 (lacking the C1 central
      microtubule) have reduced microtubule-sliding velocity compared with wild-type
      axonemes. Based on functional analyses of axonemes isolated from radial spokeless
      mutants, we hypothesized that inhibitors of casein kinase 1 (CK1) and cAMP
      dependent protein kinase (PKA) would rescue dynein activity and increase
      microtubule-sliding velocity in central pairless mutants. Treatment of axonemes
      isolated from both pf18 and pf16 with DRB, a CK1 inhibitor, but not with PKI, a
      PKA inhibitor, restored dynein activity to wild-type levels. The DRB-induced
      increase in dynein-driven microtubule sliding was inhibited if axonemes were
      first incubated with the phosphatase inhibitor, microcystin. Inhibiting CK1 in
      pf15 axonemes, which lack the central pair as well as PP2A [Yang et al., 2000: J.
      Cell Sci. 113:91-102], did not increase microtubule-sliding velocity. These data
      are consistent with a model in which the central apparatus, and specifically the
      C1 microtubule, regulate dynein through interactions with the radial spokes that
      ultimately alter the activity of CK1 and PP2A. These data are also consistent
      with localization of axonemal CK1 and PP2A near the dynein arms.

PMID- 11977082
TI  - In vivo localization of centrin in the green alga Chlamydomonas reinhardtii.
AB  - The green alga Chlamydomonas reinhardtii has been used as a model system to study
      flagellar assembly, centriole assembly, and cell cycle events. These processes
      are dynamic. Therefore, protein targeting and protein-protein interactions should
      be evaluated in vivo. To be able to study dynamic processes in C. reinhardtii in
      vivo, we have explored the use of the green fluorescent protein (GFP). A
      construct containing a fusion of centrin and GFP was incorporated into the genome
      as a single copy. The selected clone shows expression in 25-50% of the cells.
      Centrin-GFP was targeted in vivo to the nuclear basal body connectors and the
      distal connecting fibers. At the electron microscopic level, it was also
      localized to the flagellar transitional regions. EM data of transformants
      indicate that there are some abnormalities in the centrin-containing structures.
      The transitional region consists of only the transverse septum or has lesions in
      the H-piece. The distal connecting fibers are thinner and their characteristic
      crossbands seem to be incomplete. Deflagellation is not affected since more than
      95% of the cells deflagellate. Also basal body segregation is not affected since
      cells with an abnormal flagellar number were not detected. Functional studies of
      the centrin-GFP fusion show the characteristic calcium-induced mobility shift in
      SDS-PAGE. Immunofluorescence revealed that during cell division, centrin-GFP
      remains associated with the basal bodies. In vivo localization of the fusion
      protein during cell division shows that in metaphase centrin-GFP appears as two
      opposing spots located close to the spindle poles. The distance between the spots
      increases as the cells progress through anaphase and then decreases during
      telophase. GFP is a useful tool to study dynamic processes in the cytoskeleton of
      C. reinhardtii.

PMID- 11977091
TI  - Myosin Va is locally synthesized following nerve injury.
AB  - The presence of Myosin Va (an actin-based molecular motor) in the peripheral
      nervous system was examined and its subcellular distribution within the axons of
      the sciatic nerve was demonstrated via immunocytochemistry. Myosin Va (M-Va) in
      the nerve was detected by using SDS-PAGE and Western blot techniques with a
      polyclonal antibody specifically raised against the M-Va globular tail domain. In
      addition, purification of M-Va from the rat sciatic nerve prior to immunoblotting
      yielded a M-Va standard band. Likewise, optical immunocytochemical procedures
      revealed the presence of M-Va, particularly in the cortical axoplasmic territory,
      but also in the Schwann cell soma. The above experiments were carried out both on
      intact as well as on severed sciatic nerves with similar results. The proximal
      stumps of severed sciatic nerves (from 0 to 72 h after injury) were labelled in
      vivo with (35)S-methionine. SDS-PAGE autoradiography of the immunoabsorbed M-Va
      from the radiolabelled homogenized nerve tissue showed a significant increment of
      the radioactive intensity of M-Va heavy chain band through time. Moreover, a
      significant increment of transcripts coding for M-Va heavy chain was detected
      through time using RT-PCR after nerve injury and compared to intact nerves. This
      data suggest that M-Va is up-regulated in a time-dependent manner. The latter
      suggests a possible involvement of M-Va in nerve regeneration processes.

PMID- 11977092
TI  - Transient production of alpha-smooth muscle actin by skeletal myoblasts during
      differentiation in culture and following intramuscular implantation.
AB  - alpha-smooth muscle actin (SMA) is typically not present in post-embryonic
      skeletal muscle myoblasts or skeletal muscle fibers. However, both primary
      myoblasts isolated from neonatal mouse muscle tissue, and C2C12, an established
      myoblast cell line, produced SMA in culture within hours of exposure to
      differentiation medium. The SMA appeared during the cells' initial elongation,
      persisted through differentiation and fusion into myotubes, remained abundant in
      early myotubes, and was occasionally observed in a striated pattern. SMA
      continued to be present during the initial appearance of sarcomeric actin, but
      disappeared shortly thereafter leaving only sarcomeric actin in contractile
      myotubes derived from primary myoblasts. Within one day after implantation of
      primary myoblasts into mouse skeletal muscle, SMA was observed in the myoblasts;
      but by 9 days post-implantation, no SMA was detectable in myoblasts or muscle
      fibers. Thus, both neonatal primary myoblasts and an established myoblast cell
      line appear to similarly reprise an embryonic developmental program during
      differentiation in culture as well as differentiation within adult mouse muscles.

PMID- 11977093
TI  - Quantification of Shigella IcsA required for bacterial actin polymerization.
AB  - Shigella move through the cytoplasm of host cells by active polymerization of
      host actin to form an "actin tail." Actin tail assembly is mediated by the
      Shigella protein IcsA. The process of Shigella actin assembly has been studied
      extensively using IcsA-expressing Escherichia coli in cytoplasmic extracts of
      Xenopus eggs. However, for reasons that have been unclear, wild type Shigella
      does not assemble actin in these extracts. We show that the defect in actin
      assembly in Xenopus extracts by Shigella can be rescued by increasing IcsA
      expression by approximately 3-fold. We calculate that the number of IcsA
      molecules required on an individual bacterium to assemble actin filaments in
      extracts is approximately 1,500-2,100 molecules, and the number of IcsA molecules
      required to assemble an actin tail is approximately 4,000 molecules. The majority
      of wild type Shigella do not express these levels of IcsA when grown in vitro.
      However, in infected host cells, IcsA expression is increased 3.2-fold, such that
      the number of IcsA molecules on a significant percentage of intracellular wild
      type Shigella would exceed that required for actin assembly in extracts. Thus,
      the number of IcsA molecules estimated from our studies in extracts as being
      required on an individual bacterium to assemble actin filaments or an actin tail
      is a reasonable prediction of the numbers required for these functions in
      Shigella-infected cells.

PMID- 11977094
TI  - The Chlamydomonas MBO2 locus encodes a conserved coiled-coil protein important
      for flagellar waveform conversion.
AB  - Chlamydomonas flagella can undergo a calcium-dependent conversion between an
      asymmetric ciliary waveform and a symmetric flagellar waveform. Mutations at
      three MBO loci abolish the predominant ciliary waveform and result in cells that
      move backward only with the flagellar waveform. We have cloned and characterized
      the MBO2 gene. It encodes a novel protein with extensive alpha-helical coiled
      coils and two leucine zippers. Sequences highly similar to MBO2p were found in a
      variety of organisms with cilia and flagella, suggesting that the MBO2 gene
      function may be conserved in many diverse taxa. Antibodies to MBO2p recognized an
      axonemal protein of 110 kDa, which appeared to be tightly associated with doublet
      microtubules. The protein was present in flagella of a variety of paralyzed
      flagellar mutants that lacked different axonemal structures, indicating that
      MBO2p is a component of a previously uncharacterized flagellar protein complex.
      In contrast to the earlier suggestion that the MBO2 gene may encode a component
      of an intramicrotubular beak-like structure present only proximally in flagella,
      we localized an epitope-tagged MBO2p along the entire length of the flagella.
      Moreover, the insertion of a hemagglutinin (HA) epitope in the conserved C
      terminal domain of MBO2p reduced the swimming velocity of cells transformed with
      the epitope-tagged gene. These results indicate that MBO2p may play a role both
      in the assembly of the beak-like structure and the regulation of the force
      generation machinery during the ciliary beat.

PMID- 11977095
TI  - Video-microscopy observations of fast dynamic processes in the protozoon Giardia
      lamblia.
AB  - Video-microscopy in combination with digital image processing was used to analyze
      dynamic processes associated to the life cycle of Giardia lamblia trophozoites.
      These parasites swim and attach to the epithelial cells, producing the disease
      known as Giardiasis. Giardia is a multiflagellar cell, presenting 4 pairs of
      flagella. With the use of analogue and digital tools, we observed that in cells
      attached to glass slides only 2 of the 4 pairs present active beating (wave
      propagation). The frequency observed was 17-18 Hz to the anterior and 8-11 Hz to
      the ventral flagella. These data resulted from several hours of recording using
      both analogue video and high-speed digital camera. The caudal pair did not show
      active beating patterns and the same holds true for the posterior one. In this
      latter pair, oscillations were observed, but they were always associated to the
      transit of the wave produced by the ventral pair. The analysis performed with
      free moving cells showed that during its forward dislocation, Giardia lamblia
      presented either a lateral rocking or a complete rotational (tumbling) movement
      around its longitudinal axis. A dislocation of the caudal region of the cell both
      in the lateral and dorso-ventral direction was observed. This movement was
      completely independent from the flagellar beating and it is likely to be produced
      by a microtubular complex located in the caudal portion of the cell. The adhesion
      process of Giardia lamblia was also followed by video-microscopy and the data
      showed that the ventral disk had an active participation in this process.

PMID- 11977096
TI  - Pharmaceutical applications of micro-thermal analysis.
AB  - Micro-thermal analysis is a recently introduced thermoanalytical technique that
      combines the principles of scanning probe microscopy with thermal analysis via
      replacement of the probe tip with a thermistor. This allows samples to be
      spatially scanned in terms of both topography and thermal conductivity, whereby
      placing the probe on a specific region of a sample and heating, it is possible to
      perform localized thermal analysis experiments on those regions. In this
      minireview, the principles of the technique are outlined and the current uses
      within the polymer sciences described. Current pharmaceutical applications are
      then discussed; these include the identification of components in compressed
      tablets, the characterization of drug-loaded polylactic acid microspheres, the
      analysis of tablet coats, and the identification of amorphous and crystalline
      regions in semicrystalline samples. The current strengths and weaknesses of the
      technique are outlined, along with a discussion of the future directions in which
      the approach may be taken.

PMID- 11977097
TI  - Amphiphilic beta-cyclodextrins modified on the primary face: synthesis,
      characterization, and evaluation of their potential as novel excipients in the
      preparation of nanocapsules.
AB  - The purpose of this study was to synthesize and characterize amphiphilic beta
      cyclodextrins modified on the primary face with substituents of varying chain
      lengths (C6 and C14) and bond types (ester or amide). We also aimed to evaluate
      the potentiality of the new amphiphilic beta-cyclodextrins as excipients for the
      preparation and optimization of nanocapsules without using surface-active agents.
      Amphiphilic beta-cyclodextrin derivatives were characterized by (1)H-nuclear
      magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, mass
      spectroscopy, differential scanning calorimetry, and elemental analysis.
      Nanocapsules prepared by nanoprecipitation were characterized by particle size
      and zeta potential determination and freeze fracture followed by transmission
      electron microscopy. The appropriate amphiphilic beta-cyclodextrin and its
      optimum concentration to be used were determined. Formation and characteristics
      of the nanocapsules were highly dependent on the structural properties of the
      modified cyclodextrin, its behavior in the oil-water interface and the viscosity
      and miscibility of the organic solvent with water. Physical stability after 5
      month storage was also evaluated. The results indicated that derivatives with 6C
      aliphatic chains on the primary face proved to be the most efficient among the
      amphiphilic beta-CDs in this study. They avoid the use of surfactants in
      parenteral formulations of nanocapsules.

PMID- 11977098
TI  - Evidence of lipoplex dissociation in liquid formulations.
AB  - Aggregation is typically cited as the root cause of lipoplex transfection
      efficacy loss in liquid formulations. Typically, this conclusion is based on
      observed increases in lipoplex hydrodynamic size. A more detailed physical
      characterization of the lipoplex transfection efficacy diminution has previously
      never been conducted. As a result, most research has focused on either methods of
      forming more stable lipoplex formulations or preservation methods such as
      lyophilization. These studies typically consider the use of stabilizing
      additives, such as polymer and sugar molecules, to enhance the efficacy of
      lipoplex dispersions. This report details a recent multiangle laser light
      scattering study of the temporal evolution of lipoplex geometric size (i.e.,
      radius of gyration) and molar mass in liquid-based formulations over several
      months. The results indicate that for the lipoplex systems considered, the
      primary factor underlying the long-term loss of lipoplex transfection efficiency
      is actually lipoplex dissociation caused by a decrease in the observed molar mass
      of some lipoplex formulations. The increasing geometric sizes observed are
      actually the result of lipoplex dissociation combined with an increase in volume.
      That is, the lipoplexes lose mass and expand in volume, leading to a less dense
      lipoplex structure over time.

PMID- 11977099
TI  - Cell association of liposomes with high fluid anionic phospholipid content is
      mediated specifically by LDL and its receptor, LDLr.
AB  - We have sought to confirm indications in our recent studies suggesting that
      association of liposomes composed of 75-100 mol % egg phosphatidylglycerol (ePG),
      a fluid anionic phospholipid, with cells is mediated by low density lipoprotein
      (LDL) and the classical LDL receptor (LDLr). In the present study, binding of
      liposomes composed of 75-100 mol % ePG to CV1-P cells, either in serum
      supplemented medium or in defined medium supplemented with LDL, is blocked by the
      presence of either of two monoclonal antibodies. The first is immunoglobulin
      (Ig)G C7, an antibody specific for LDLr. The second is IgG 5E11, an antibody
      specific for domain 3441-3569 of apolipoprotein B100. CHOldlA7, a cell line known
      to lack the LDLr and previously shown by us to associate minimally with 75-100
      mol % ePG liposomes, was transfected with the human LDLr. The transfected cells
      bound 75-100 mol % ePG liposomes at high levels, and this binding was blocked by
      IgG C7. Previously, we have shown that serum, but not LDL or high density
      lipoprotein, induces association of 25-50 mol % ePG liposomes with both CV1-P and
      CHO wild type cells, but not CHOldlA7. In the present study, IgG C7 does not
      block this interaction, and transfected CHOldlA7 cells do not show this
      interaction. Hence, this form of liposome binding appears not to involve LDL or
      LDLr, but requires a receptor, currently unknown, and a serum component other
      than LDL or high density lipoprotein. The unknown receptor, in addition to LDLr,
      is missing from CHOldlA7.

PMID- 11977100
TI  - Controlled release of interleukin-2 from chitosan microspheres.
AB  - Chitosan microspheres were evaluated for sustained-release of recombinant human
      interleukin-2 (rIL-2) in this study. In addition, the effects of different
      formulation factors, such as chitosan and protein concentrations, the volume of
      sodium sulfate solution, addition technique of rIL-2, and presence of
      glutaraldehyde during the encapsulation process, on microsphere characteristics
      were investigated. Chitosan microspheres containing rIL-2 were prepared by using
      the precipitation technique. The average diameter of microspheres was between
      1.11-1.59 microm. Recombinant IL-2 encapsulation efficiency in these microspheres
      was high (75-98%). Formulation factors had no effect on the microsphere size.
      Recombinant IL-2 had been released from chitosan microspheres over a period of 3
      months. The encapsulated rIL-2 remained biologically active and could be
      completely recovered from the release medium. Briefly, rIL-2 was released from
      chitosan microspheres in a sustained manner. The efficacy of rIL-2 loaded
      chitosan microspheres was studied using two model cells, HeLa and L-strain cell
      lines. Chitosan microspheres were added to the cells at different concentrations,
      and the amount of rIL-2 was assayed using the ELISA kit. Cell culture studies
      indicated that microspheres were uptaken by cells, and rIL-2 was released from
      the microspheres. Cellular uptake of rIL-2-loaded microspheres was dose
      dependent. It can be said that chitosan microsphere is a suitable carrier for rIL
      2 delivery.

PMID- 11977101
TI  - Pharmacokinetics and tissue distribution of a new partricin A derivative (N
      dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diaspartate) in mice.
AB  - A single-dose trial in mice (1.25 mg/kg SPA-S-753 or 1 mg/kg amphotericin B [AmB]
      by intravenous route) was performed to study the pharmacokinetics, tissue
      distribution, and urinary excretion of a new polyene, SPA-S-753 (N
      dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diaspartate), in
      comparison with AmB. Antibiotic concentrations were determined by microbiological
      assay (agar diffusion method). The elimination half-lives in serum were 15.1 and
      19.8 h, respectively, for SPA-S-753 and AmB; the area under the curve from 0 to
      infinity values were 49.3 for SPA-S-753 and 23.6 microg. h/mL for AmB, because of
      the higher serum levels of SPA-S-753 found just after administration. The tissue
      concentrations of SPA-S-753 were lower than those of AmB in liver and lungs but
      higher in the kidneys. The urine concentrations of SPA-S-753 and the percent of
      the administered dose recovered from the urine were quite low in mice, whereas
      those of AmB were higher.

PMID- 11977102
TI  - A new method for drug transport studies on pig nasal mucosa using a horizontal
      Ussing chamber.
AB  - The horizontal Ussing chamber method described here allows performance of
      transport studies on pig nasal respiratory mucosa under conditions simulating
      reality in that it mimics the air-mucosa interface. The transport of testosterone
      and mannitol through pig nasal mucosa in the horizontal Ussing chamber was
      investigated using both liquid and air mucosal interfaces. There were no
      significant differences in either the bioelectrical parameters (transmucosal
      electrical resistance, R, potential difference, PD, and short circuit current,
      I(sc)) or the apparent permeability (P(app)) of the mucosa to testosterone or
      mannitol between the liquid and air interface experiments. The histological study
      showed that the epithelial cell layer tolerates exposure to the air interface
      well. The P(app) equation was developed to correct for substance binding to the
      wall of the receiver chamber. The mean values +/- SD of R, PD, and I(sc) for the
      mucosae in the study were 75.0 +/- 28.0 Omegacm(2), (-4.53) +/- 3.46 mV and 58.6
      +/- 28.8 microA/cm(2), respectively. The corrected P(app) for testosterone with
      and without the mucosal air interface were 9.82. 10(-6) +/- 11.41. 10(-6) cm/s
      and 32.24. 10(-6) +/- 31.12. 10(-6) cm/s, respectively. The P(app) values for
      mannitol with and without the air interface were 2.26. 10(-6) +/- 1.42. 10(-6)
      cm/s and 3.12. 10(-6) +/- 1.72. 10(-6) cm/s, respectively.

PMID- 11977103
TI  - Isolation and structural elucidation of degradation products of alprazolam:
      photostability studies of alprazolam tablets.
AB  - Accelerated thermal, hydrolytic, and photochemical degradations of alprazolam
      were performed under several reaction conditions. The stress studies revealed the
      photolability of the drug as the most adverse stability factor; the main
      photodegradation products were isolated and properly characterized as:
      triazolaminoquinoleine; 5-chloro-[5"-methyl-4H-1,2,4-triazol-4-yl]benzophenone,
      and 1-methyl-6-phenyl-4H-s-triazo-[4,3-alpha][1,4]benzodiazepinone. Accelerated
      pH-dependent studies show that the photoinstability increases as the pH
      decreases; at pH 9.0, photodegradation does not occur, therefore, the
      photochemical degradation of alprazolam was performed in buffered solutions at pH
      2.0 and 3.6. The higher rate of reaction was observed at pH = 2.0; consequently,
      acidic conditions should be avoided and appropriate light protection is
      recommended during the drug-development process, storage, and handling. The main
      degradation route for alprazolam tablets is also photochemical.

PMID- 11977104
TI  - Solubility prediction in supercritical CO(2) using minimum number of experiments.
AB  - The correlation ability and solubility prediction in supercritical carbon dioxide
      of a proposed equation were studied. The work involved the solubilities of
      nicotinic acid and p-acetoxyacetanilide in supercritical carbon dioxide using a
      dynamic flow solubility system at 35-75 degrees C and 100-200 bar. The generated
      experimental solubility data together with 21 data sets collected from the
      literature were used to evaluate the correlation ability of available empirical
      equations. The average absolute relative deviations (AARD) for the empirical
      equations are 12.6-24.8%. The prediction capability of the modified empirical
      relationship was studied with six experimental data points as a training set.
      Then, solubility at other temperatures and pressures were predicted. The AARD
      between predicted solubilities and observed values is 17%.

PMID- 11977105
TI  - Effect of permeation enhancer pretreatment on the iontophoresis of luteinizing
      hormone releasing hormone (LHRH) through human epidermal membrane (HEM).
AB  - A 2 x 2 factorial design was performed to determine the effect of a permeation
      enhancer (oleic acid/propylene glycol), iontophoresis (2 V), and the combination
      of the two treatments on the permeation enhancement of a model peptide, LHRH
      (luteinizing hormone releasing hormone), through human epidermal membrane (HEM).
      In parallel studies, TEAB (tetraethylammonium bromide, a small ionic solute) and
      sucrose (an electroosmotic flow marker) were also investigated. Structural
      changes in the HEM were monitored via conductance measurements, differential
      scanning calorimetry (DSC), and infrared (IR) spectroscopy experiments. LHRH
      enhancement due to enhancer in combination with iontophoresis (I + E; 29.5 times
      passive permeability, P), was greater than during iontophoresis alone (I; 14.3)
      and enhancer treatment alone (E; 3.5). I + E had an additive effect of I and E,
      indicating the mechanisms of action of the individual enhancement strategies were
      likely to be located at different sites in the skin. Also, no synergistic
      enhancement was observed with I + E for either TEAB or sucrose. For TEAB,
      permeability enhancement due to I (approximately 1400) was much higher than that
      due to E (14.9), and no additive effect could be detected. For sucrose, E had no
      effect on either passive or iontophoretic permeability, eliminating the
      possibility that electroosmosis could explain increases in LHRH permeability.
      Evidence of synergy between E and I was found, with conductance measurements
      indicating that I + E synergistically increased the membrane permeability to
      conducting ions (Na+ and Cl-). It appears these pathways were not available for
      transport for the solutes used in the current study. DSC and IR investigations
      showed significant changes in stratum corneum lipid structure following E
      treatment but not following I. These findings probably arise from the localized
      action of iontophoresis compared with the bulk action of enhancer. In summary,
      increased LHRH delivery through HEM in vitro can be achieved using an enhancer in
      combination with iontophoresis.

PMID- 11977106
TI  - Preparation and crystal structure of a trihydrate of paracetamol.
AB  - This work reports the preparation and crystal structure of a trihydrate of
      paracetamol. Crystals were grown by slow cooling of an aqueous solution of
      paracetamol to 0 degrees C. Single-crystal X-ray diffraction shows that the
      trihydrate crystallizes in the orthorhombic crystal system, space group Pbca, Z =
      8, a = 7.3324(16), b = 12.590(3), c = 22.636(6) A, V = 2089.7(9) A(3). The
      crystals of the trihydrate dehydrate rapidly at 20 degrees C to give anhydrous
      paracetamol as its monoclinic form.

PMID- 11977107
TI  - Comparison of skin stripping, in vitro release, and skin blanching response
      methods to measure dose response and similarity of triamcinolone acetonide cream
      strengths from two manufactured sources.
AB  - The collective studies compare in vitro drug release, in vivo skin stripping, and
      skin blanching response methods for dose responsiveness and bioequivalence
      assessment of triamcinolone acetonide cream products, as a function of
      application duration, drug concentration, and manufacturer source. Commercially
      available triamcinolone acetonide creams (0.025%, 0.1%, and 0.5%) from two
      manufacturers were evaluated in vitro for rate and extent of drug release across
      synthetic membranes and in vivo for rate, extent, and variability of drug uptake
      into human stratum corneum and skin blanching response in human forearm skin.
      Data demonstrate that increasing triamcinolone acetonide cream concentration
      applied increased the rate and extent of drug released in vitro as well as the
      extent of drug uptake and skin blanching response in human skin in vivo. No
      difference (p < 0.05) between the two sources of 0.1% or 0.5% creams was measured
      by the skin stripping or skin blanching response methods. Dermatopharmacokinetic
      analysis of triamcinonide acetonide in vivo is therefore dose responsive to drug
      concentration applied and application duration and agrees with in vivo skin
      blanching results. Data support the use of dermatopharmacokinetic methods for
      bioequivalence and bioavailability assessment of topical drug products.

PMID- 11977108
TI  - Pharmacokinetics and tissue distribution of idarubicin-loaded solid lipid
      nanoparticles after duodenal administration to rats.
AB  - Idarubicin-loaded solid lipid nanoparticles (IDA-SLN) and idarubicin in solution
      were prepared and the two formulations were administered to rats, either by the
      duodenal route or intravenously (iv). The aim of this research was to study
      whether the bioavailability of idarubicin can be improved by administering IDA
      SLN duodenally to rats. Idarubicin and its main metabolite idarubicinol were
      determined in plasma and tissues by reversed-phase high-performance liquid
      chromatography. The pharmacokinetic parameters of idarubicin found after duodenal
      administration of the two formulations were different: area under the curve of
      concentration versus time (AUC) and elimination half-life were approximately 21
      times and 30 times, respectively, higher after IDA-SLN administration than after
      the solution administration. Tissue distribution also differed: idarubicin and
      idarubicinol concentrations were lower in heart, lung, spleen, and kidneys after
      IDA-SLN administration than after solution administration. The drug and its
      metabolite were detected in the brain only after IDA-SLN administration,
      indicating that SLN were able to pass the blood-brain barrier. After iv IDA-SLN
      administration, the AUC of idarubicin was lower than after duodenal
      administration of the same formulation. Duodenal administration of IDA-SLN
      modifies the pharmacokinetics and tissue distribution of idarubicin. The IDA-SLN
      act as a prolonged release system for the drug.

PMID- 11977109
TI  - Pharmacodynamic interaction of recombinant human interleukin-10 and prednisolone
      using in vitro whole blood lymphocyte proliferation.
AB  - Prednisolone, a commonly used synthetic corticosteroid, and IL-10, a cytokine
      under investigation for strong antiinflammatory properties, are being
      contemplated as a potential joint therapeutic regimen in immune disorders. Their
      pharmacodynamic interactions were examined in blood from healthy adult male and
      female volunteers using an in vitro phytohemagglutinin (PHA)-stimulated whole
      blood lymphocyte proliferation technique. Isobolograms along with parametric
      competitive and noncompetitive interaction models were used to determine the
      nature and intensity of interactions. Single drug effects show prednisolone more
      efficacious in inhibiting lymphocyte proliferation with an IC(50) of 3.3 ng/mL
      and I(max) value of 1, signifying complete suppression. Analogous parameters for
      IL-10 were 16.2 ng/mL for IC(50) and 0.89 for I(max). There were no significant
      differences in the single drug immunosuppressive effects among genders. Their
      joint effects showed additive interaction based on isobolographic analysis.
      Parametric analysis using the competitive interaction model described their
      interaction as slightly synergistic, while the noncompetitive interaction
      modeling indicate a small degree of antagonism. Also, the joint effects in
      females tend to be more antagonistic than males. Concomitant use of prednisolone
      and IL-10 should thus reflect the net additive responses to concentrations of
      each agent.

PMID- 11977110
TI  - Systemic absorption of topical lidocaine in normal volunteers, patients with post
      herpetic neuralgia, and patients with acute herpes zoster.
AB  - Topical lidocaine has been recently marketed as a new treatment for post-herpetic
      neuralgia. The aim of our study was to characterize the absorption profile of and
      systemic exposure to lidocaine from patch and gel formulations in normal
      volunteers, patients with post-herpetic neuralgia, and patients with acute herpes
      zoster. The bioavailability of lidocaine from the patch formulation averaged 3%,
      and was similar after single and repeated doses. Systemic exposure to lidocaine
      and monoethylglycinexylidide (MEGX), the primary active metabolite of lidocaine,
      after application of lidocaine gel or patches was minimal in normal volunteers,
      patients with post-herpetic neuralgia, and patients with acute herpes zoster.
      Considering the benefit versus risk of topical lidocaine, systemic absorption and
      toxicity of lidocaine seems not to be a significant risk.

PMID- 11977111
TI  - Hydration-induced proton transfer in the solid state of norfloxacin.
AB  - Norfloxacin is a special compound. Its hydrate form seems to be more soluble in
      water than in the anhydrate form. To investigate the hydration behavior of
      norfloxacin, the moisture-sorption analysis of anhydrous norfloxacin in different
      humidities was determined by using differential scanning calorimetry and
      thermogravimetric analysis. The contents of free water and bound water in the
      moisture-equilibrated norfloxacin were estimated quantitatively by using a curve
      fitting program. Fourier transform infrared microspectroscopy with or without
      thermal analyzer was used to examine the structural change and dehydration
      process of norfloxacin in different humidities. The result indicates that the
      water content sorbed to anhydrous norfloxacin changed lightly below 51% relative
      humidity (RH) but increased markedly beyond 51% RH. The content of free water in
      the moisture-equilibrated norfloxacin was nearly to zero below 55% RH, but
      increased dramatically in high humidity. The content of bound water also enhanced
      gradually with the external humidity and reached to a constant of one unit after
      > 75% RH. When norfloxacin anhydrate transformed to its hydrate, the infrared
      peak intensity at 1732 and 1253 cm(-1) assigned to the C=O and C-O groups of
      carboxylic acid decreased gradually with the increase of water content, but the
      infrared peak intensity at 1584 and 1339 cm(-1) corresponding to asymmetric and
      symmetric carboxylates increased. Furthermore, the peak at 2553 cm(-1) assigned
      to the NH(+)(2) also appeared clearly and shifted from 2558 cm(-1) in higher
      water content and humidity. The main functional groups of norfloxacin changed
      from COOH to COO(-) and NH to NH(+)(2), attributable to the proton transfer from
      COOH group to NH group. This suggests that the hydration can induce the
      interaction between norfloxacin molecules from hydrogen bonding to ionic bonding
      by a proton-transfer process in the solid state.

PMID- 11977112
TI  - Prediction of pharmacokinetics prior to in vivo studies. II. Generic
      physiologically based pharmacokinetic models of drug disposition.
AB  - Many in vitro data on physicochemical properties and specific absorption,
      distribution, metabolism, and elimination (ADME) processes are already available
      at early stages of drug discovery. These data about new drug candidates could be
      integrated/connected in physiologically based pharmacokinetic (PBPK) models to
      estimate a priori the overall plasma and tissue kinetic behaviors under in vivo
      conditions. The objective of the present study was to illustrate that generic
      PBPK models integrating such data can be developed in drug discovery prior to any
      in vivo studies. This approach was illustrated with three example compounds,
      including two lipophilic bases (diazepam, propranolol) and one neutral more
      hydrophilic drug (ethoxybenzamide). Distribution and liver metabolism were the
      processes integrated in the generic rat PBPK models of disposition. Tissue:plasma
      partition coefficients (P(t:p)s) used for description of distribution were
      estimated from established tissue composition-based equations, which need only in
      vitro data on drug lipophilicity and plasma protein binding as sole input
      parameters. Furthermore, data on intrinsic clearance (CL(int)) determined in
      vitro with hepatocytes were scaled to the in vivo situation to estimate hepatic
      metabolic clearance. These prediction approaches were both incorporated in the
      PBPK models to enable automated estimation of distribution and liver metabolism
      for each drug studied. The generic PBPK models suggested can simulate a priori
      concentration-time profiles of plasma and several tissues after intravenous
      administrations to rat. The results indicate that most of the simulated
      concentration-time profiles of plasma and 10 tissues are in reasonable agreement
      with the corresponding experimental data determined in vivo (less than a factor
      of two). However, some more relevant deviations were observed for specific
      tissues (brain and gut for diazepam; liver and gut for ethoxybenzamide; lung for
      propranolol) because of important ADME processes were probably neglected in the
      PBPK models of these drugs. In this context, generic PBPK models were also used
      for mechanistic evaluations of pharmacokinetics for generating research
      hypotheses to understand these deviations. Overall, the present generic and
      integrative PBPK approach of drug disposition suggested as a tool for a priori
      simulations and mechanistic evaluations of pharmacokinetics has the potential to
      improve the selection and optimization of new drug candidates.

PMID- 11977113
TI  - Enhancements in gene expression by the choice of plasmid DNA formulations
      containing neutral polymeric excipients.
AB  - Formulations containing maltodextrin (2% w/v) were identified to facilitate
      intramuscular (im) delivery of plasmid DNA in mice using the reporter genes
      luciferase and chloramphenicol acetyltransferase (CAT) and the therapeutic gene
      of erythropoietin (EPO) as monitors of transfection efficiency. Even though
      considerable variability in gene expression was observed in animals, a 5-8-fold
      enhancement of reporter gene expression was observed with this excipient compared
      with saline formulations of DNA. In a therapeutically significant experiment, a
      single im injection of an EPO plasmid formulation containing 2% (w/v)
      maltodextrin resulted in a significant and prolonged elevation of the hematocrit
      levels of mice compared with control DNA in saline. Biophysical studies with
      Fourier transform infrared (FTIR) spectroscopy, isothermal titration, and
      differential scanning calorimetry (DSC) suggested a weak interaction between DNA
      and maltodextrin as well as a thermal stabilizing effect on the DNA. These in
      vivo and biophysical results with maltodextrin are comparable to those reported
      previously with other nonionic polymers, such as poly(vinyl pyrrolidone) and
      poloxamers, and indicate that maltodextrin is an additional nonionic excipient
      that displays the property of gene expression enhancement.

PMID- 11977114
TI  - Distribution of calcitonin gene-related peptide-like immunoreactivity in the
      brain of the lizard Podarcis hispanica.
AB  - The present work studies the distribution of calcitonin gene-related peptide
      immunoreactive (CGRP-li) neurons and fibers in the brain of a reptile, the lizard
      Podarcis hispanica. CGRP-li perikarya were not present in the telencephalon. In
      the thalamus, CGRP-li perikarya were restricted to the posteromedial and
      posterolateral nuclei. In the hypothalamus, CGRP-li cells were found mainly in
      the supramammillary and mammillary nuclei. In the midbrain and brainstem, CGRP-li
      cells appeared in the ventral tegmental area, the parabrachial nucleus, and the
      motor nuclei of the III-VII, IX, X, and XII cranial nerves. Motoneurons of the
      ventral horn of the spinal cord were also immunoreactive for CGRP. CGRP-li fibers
      were seen in the telencephalic hemispheres, where a dense plexus of reactive
      fibers appeared in the septum and in the lateral striatoamygdaloid transition
      area. From the latter, CGRP-li fibers entered the posterior dorsal ventricular
      ridge, the cell layer and deep stratum of the ventral lateral cortex, and various
      amygdaloid nuclei. Parts of the striatum (nucleus accumbens) and pallidum also
      displayed CGRP-li innervation. In the diencephalon, CGRP-li innervation was
      observed in parts of the dorsal thalamus and in the periventricular and medial
      hypothalamus. The pretectum and deep layers of the optic tectum also showed CGRP
      li fibers, and numerous CGRP-li fibers were observed in the midbrain central
      gray, tegmentum, and pons. Some of the sensory fibers of the trigeminal, vagal,
      and spinal nerves were also CGRP-li. These results show that the distribution of
      CGRP-li structures in the reptilian brain is similar to that described for other
      vertebrates and suggest that the thalamotelencephalic CGRPergic projections
      appear to be conserved among amniote vertebrates.

PMID- 11977115
TI  - Retinofugal projections in the short-tailed opossum (Monodelphis domestica).
AB  - In the current investigation, retinofugal projections to midbrain and thalamic
      nuclei of Monodelphis domestica were investigated using wheat-germ agglutinin
      conjugated to horseradish peroxidase (WGA-HRP). Large intraocular injections of
      WGA-HRP were placed into the eye, and patterns of labeled axon terminals were
      related to nuclear boundaries in tissue that was stained for Nissl or reacted for
      cytochrome oxidase (CO). Our results demonstrate that the major projection from
      the retina is to the contralateral dorsal lateral geniculate nucleus (LGNd) and
      the superior colliculus (SC). Connections were also observed with the
      contralateral pretectal nucleus (PRT), the lateral posterior nucleus (LP), and
      the ventral division of the lateral geniculate nucleus (LGNv). Ipsilateral
      connections were with the LGNv and LGNd. These findings are consistent with
      reports in other marsupials as well as with studies in a number of eutherian
      mammals. Thus, there appears to be a common pattern of retinofugal projections
      that all mammals share, probably due to retention from a common ancestor.
      However, some features such as a lack of ipsilateral input to the SC (which are
      absent only in certain species like Monodelphis, platypus, and echidnas) may
      represent a primitive state retained from a common ancestor. When comparisons of
      retinofugal connections and LGNd organization are made across taxa, three types
      of organization are observed: a homogenous LGNd with a high degree of binocular
      overlap of projections; a partially differentiated LGNd with some segregation of
      eye-specific inputs; and a fully segregated structure with a large degree of
      segregation of eye-specific inputs. We discuss the factors that contribute to the
      organization observed in extant mammals and conclude that phylogeny and lifestyle
      appear to be the underlying factors contributing to the organization of the LGNd.

PMID- 11977116
TI  - Increase in descending brain-spinal cord projections with age in larval lamprey:
      implications for spinal cord injury.
AB  - The purpose of this study was to determine whether new descending brain-spinal
      cord projections are added with age in larval lamprey and might contribute
      substantially to restoration of these projections following spinal cord injury.
      Retrograde horseradish peroxidase (HRP) labeling of descending brain neurons was
      performed in "young" and "old" larval lamprey that differed in age by at least
      one year. In old larval lamprey, significantly more descending brain neurons
      projected to specific rostral levels of the spinal cord than in young animals.
      Furthermore, in young and old lamprey, the main morphological change in Muller
      and Mauthner cells was an increase in soma size. The major conclusion from the
      present study is that in larval lamprey, some new brain-spinal cord projections
      are added with age that could be due to axonal elongation by preexisting brain
      neurons and/or descending projections from new neurons (i.e., neurogenesis or
      maturation of incompletely differentiated neurons). Following spinal cord
      transections, the numbers of descending projections were not significantly
      different than those in normal, unlesioned animals. Thus, some new descending
      projections are added with age, but at a relatively slow rate, and the rate does
      not appear to be affected significantly by spinal cord transections. Together,
      the present results and those from our recent double-labeling study suggest that
      following spinal cord transection in larval lamprey, axonal regeneration by
      descending brain neurons, rather than the relatively slow addition of new brain
      spinal cord projections with age, probably accounts for the majority of restored
      projections and recovery of locomotor function

PMID- 11977117
TI  - Synaptic distribution of ionotropic glutamate receptors in the inner plexiform
      layer of the primate retina.
AB  - The distribution and synaptic clustering of glutamate receptors (GluRs) were
      studied in the inner plexiform layer (IPL) of the macaque monkey retina by using
      subunit specific antisera. A punctate immunofluorescence pattern was observed in
      the IPL for all subunits tested, and electron microscopy confirmed that the
      immunoreactive puncta represent clustering of receptors at sites postsynaptic to
      the bipolar cell ribbon synapses (dyads). Usually only one of the two
      postsynaptic processes at the dyads expressed a given subunit. Immunoreactive
      GluR2, GluR2/3, and GluR4 puncta were found at high density throughout the IPL
      and are probably expressed at every dyad. The GluR1 subunit was expressed at
      lower density. The N-methyl-D-aspartate (NMDA) receptor subunits NR2A and NR1C2'
      were restricted to synapses localized in two broad bands in the center of the
      IPL. They were often colocalized with GluR2/3 and GluR4 subunits. The orphan
      receptor subunits delta 1/2 predominated in three horizontal bands. The kainate
      receptor subunits GluR6/7 were clustered in large postsynaptic densities adjacent
      to bipolar cell axon terminals but lacking a synaptic ribbon on the presynaptic
      side. This might represent a conventional synapse made by a bipolar axon
      terminal. The results suggest that GluR2/3 and GluR4, together with NMDA
      receptors, are preferentially expressed on ganglion cell dendrites, whereas
      kainate receptors and the delta 1/2 subunits are mostly localized on amacrine
      cell processes.

PMID- 11977118
TI  - High-resolution localization of clathrin assembly protein AP180 in the
      presynaptic terminals of mammalian neurons.
AB  - Synaptic vesicles (SVs) assemble at the presynaptic compartment through a
      clathrin-dependent mechanism that involves one or more assembly proteins (APs).
      The assembly protein AP180 is especially efficient at facilitating clathrin cage
      formation, but its precise ultrastructural localization in neurons is unknown.
      Using immunoelectron microscopy, we demonstrate the presynaptic localization of
      AP180 in axon terminals of rat cerebellar neurons. In contrast, the assembly
      protein AP2 was associated with both the presynaptic plasma membrane and the
      cytosolic side of the membrane at postsynaptic and extrasynaptic sites.
      Furthermore, ultrastructural analysis of primate retina showed that AP180
      immunoreactivity was preferentially and highly enriched at ribbon synapses, where
      glutamate is released tonically at high levels and rapid vesicle turnover is
      essential. To maintain functional synaptic transmission, neurotransmitter-filled
      SVs must be readily available, and this requires proper reassembly of new
      vesicles. The expression of AP180, in addition to AP-2, in the clathrin-mediated
      endocytic pathway might add another level of control to SV reformation for
      efficient assembly of clathrin, effectively controlling the size of assembled
      vesicles and faithfully recovering SV-specific components.

PMID- 11977120
TI  - Intratelencephalic connections of the hippocampus in pigeons (Columba livia).
AB  - Behavioral experiments using ablation of the hippocampus are increasingly being
      used to address the hypothesis that the avian hippocampus plays a role in memory,
      as in mammals. However, the morphological basis of the avian hippocampus has been
      poorly understood. In the present study, the afferent and efferent connections of
      the hippocampus in the pigeon telencephalon were defined by injections, at
      various rostrocaudal sites, of neuronal tracers mainly into the triangular part
      located between its V-shaped layer of densely packed neurons. The major results
      obtained in the present study were as follows. 1) A topographical organization of
      the commissural projections was confirmed. These projections had two courses that
      projected to the contralateral side, one traveling through the fiber wall of the
      ventromedial telencephalon, which was the main path from neurons in the caudal
      hippocampus, and the other running down through the septohippocampal junction,
      which was the main path from neurons in the middle to rostral hippocampus. Both
      courses passed through the pallial commissure. 2) The hippocampus projected
      bilaterally to the septum, parahippocampal area (APH), and dorsolateral cortical
      area (CDL). These projections were also distributed topographically, with
      contralateral efferents crossing through the pallial commissure. 3) The
      hippocampus had ipsilateral reciprocal connections with APH, CDL, and the dorsal
      hyperstriatum. Septal afferents to the ipsilateral hippocampus were very small.
      4) Intrinsic connections were found between the triangular part of the
      hippocampus and the lateral limb of the V-shaped layer of neurons. 5) The
      hippocampus projected ipsilaterally to the ventral basal ganglia and the
      fasciculus diagonalis Brocae. In sum, these connections of the hippocampus may
      form a neuronal circuit for the processing of spatial memory in pigeons.

PMID- 11977119
TI  - Development of tyrosine hydroxylase-immunoreactive systems in the brain of the
      larval lamprey Lampetra fluviatilis.
AB  - The development of the catecholaminergic system of the brain of the lamprey
      (Lampetra fluviatilis) was studied with immunocytochemistry in a series of larvae
      of different sizes by using two different antibodies directed against tyrosine
      hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. In group 1
      larvae (length: 29-54 mm, ages: 8 months to 1.5 years), the only TH
      immunoreactive somata observed were located in the caudal wall of the recessus
      praeopticus (RP) and in the nucleus tuberculi posterioris (NTP). In group 2
      larvae (length: 55-80 mm, ages: 1.5-2.5 years), the somata of immunolabeled cells
      of the NTP give rise to fibers, most of which are ascending and terminate in the
      corpus striatum. Additional immunoreactive cells are observed in the nucleus
      praeopticus (NP), which has differentiated, and in the spinal cord. In group 3
      larvae (length: 81-110 mm, ages: 2.5-4 years), the spatial distribution of TH
      immunoreactive elements (somata, fibers, and terminals) bears many resemblances
      to that seen in the adult. Immunolabeled cells may be observed in the olfactory
      bulb, in the nucleus commissurae postopticae (NCP), and in the nucleus dorsalis
      hypothalami (NDH). Nevertheless, some groups of TH-immunoreactive cells found in
      the adult are not observed in group 3 larvae; these may appear during the
      metamorphic phase. By comparative analysis, we show that, in spite of several
      differences, the spatiotemporal sequence of appearance of TH-immunoreactive cell
      bodies and fibers in the lamprey presents many similarities to that described in
      gnathostomes.

PMID- 11977121
TI  - Partial characterization of the CD45 phosphatase cDNA in the owl monkey (Aotus
      vociferans).
AB  - CD45 is a protein tyrosine phosphatase implicated in T and B cell activation,
      differentiation, and development. It dephosphorylates specific tyrosine residues
      on its substrates, principally on the Src-family of protein tyrosine kinases,
      thus regulating T cell or B cell activation during the immune response. In this
      study, we present the partial CD45 nucleotide and deduced amino-acid sequences
      for the owl monkey (Aotus vociferens). There is 97% identity in the nucleotide
      sequence and 96% in the amino acid sequence with the human counterpart. Aotus
      CD45 undergoes alternative splicing on the extracelular N-terminal tail, and has
      several conserved features characteristic of other species. This includes the two
      Tyr phosphatase domains and some residues and/or motifs involved in docking of
      signaling molecules, intramolecular interactions, and CD45 activity and activity
      regulation (YINAS, GXGXXG, WPD, and YWP motifs, and the Cys residues). This
      suggests that the Aotus CD45 molecule is a functional enzyme and that initial
      lymphocyte activation in Aotus monkeys and humans is very similar. Together with
      previous reports from our laboratory, this work supports the contention that
      immune responses in Aotus are similar to those of humans, and supports the
      strategy for using this experimental model for studies on activation of T
      lymphocytes in response to specific antigens.

PMID- 11977123
TI  - Genetic diversity of Y-specific STRs in chimpanzees (Pan troglodytes).
AB  - Using the primers described for humans, sequences for 11 Y-specific
      microsatellites (DYS434, DYS435, DYS436, DYS437, DYS438, DYS439, GATA A10, A7.1,
      A7.2, C4, and H4 [Gusmao et al., in press]), previously described in 10 male
      chimpanzees (Pan troglodytes), were confirmed in nine additional male
      chimpanzees. Sequences for nine additional microsatellites (DYS19, DYS385I and
      II, DYS389I and II, DYS390, DYS391, DYS392, and DYS393) were determined in all 19
      male chimpanzees; homology to human Y-Short Tandem Repeat (STRs) was confirmed by
      sequencing. Good amplification results were not obtained for DYS19 and
      DYS385I/II. Two amplicons were obtained for DYS389I/II, but in contrast to
      humans, the larger fragment was not Y-specific. Moreover, no polymorphism was
      observed for DYS434, DYS435, or GATA A10. Consequently, these eight STRs were
      eliminated from further analyses, and haplotype and allele frequencies were
      estimated for the remaining 12 STRs. A high haplotype diversity value was found
      (1.000 +/- 0.017), demonstrating the usefulness and informative power of these Y
      STRs for future studies on chimpanzee population genetics.

PMID- 11977122
TI  - Effects of food availability on serum insulin and lipid concentrations in free
      ranging baboons.
AB  - The relationship between food availability and metabolic physiology was studied
      in groups of free-ranging baboons (Papio spp.) living in the Amboseli National
      Park and the Masai Mara National Reserve of Kenya. Three groups subsisted
      entirely on natural forage, while two other groups lived near tourist facilities
      and often consumed food wastes from these lodges. The refuse provided a very
      accessible food source with relatively high caloric density. Consumption of the
      refuse was associated with reduced locomotion. Sexually mature individuals from
      all five groups were sedated surreptitiously in the early morning and blood
      samples were collected. Compared to animals foraging exclusively in the wild,
      animals that supplemented their diet with the refuse items had two- to threefold
      elevations in serum insulin concentrations, as well as increased total
      cholesterol (C), HDL-C, and VLDL+LDL-C levels. No sex differences in
      physiological measures were observed except in body mass. Elevated serum insulin,
      and cholesterol and lipoprotein concentrations influence the development of
      cardiovascular disease and have been shown to be subject to dietary manipulation
      and exercise under controlled conditions. The present results suggest potentially
      deleterious effects of a highly accessible, calorically dense food source, and
      associated reduction of physical activity for baboons living in an otherwise
      natural environment.

PMID- 11977124
TI  - Multiple sirehood in free-ranging twin rhesus macaques (Macaca mulatta).
AB  - Rhesus macaque females regularly copulate with a number of partners, and produce
      a single offspring per reproductive cycle in over 99% of cases. We used
      genotyping of 10 STR markers to determine paternity in the Cayo Santiago
      population of rhesus macaques. About 1,500 monkeys have been analyzed to date,
      with their marker genotypes entered into a computerized database. These data
      enable us to report the first documented case in any cercopithecine nonhuman
      primate species of the production of twin offspring sired by different males.

PMID- 11977125
TI  - Sperm quality differences between the rainy and dry seasons in captive black
      handed spider monkeys (Ateles geoffroyi).
AB  - The present work provides an assessment of sperm measures (concentration,
      motility, viability, etc.) of three black-handed spider monkeys (Ateles
      geoffroyi) during the rainy and dry seasons in Mexico City, as well as an
      evaluation of the between-subjects variability of sperm quality. Twenty samples
      obtained by rectal electroejaculation and digested with trypsin were evaluated.
      The results showed that during the dry season (n = 9) the semen samples were of
      better quality than those obtained during the rainy season (n = 11). The
      individual animals showed differences in sperm concentration, although there were
      no differences in sperm quality.

PMID- 11977126
TI  - Why do cotton-top tamarin female helpers carry infants? A preliminary study.
AB  - Shortly after giving birth, cotton-top tamarin mothers frequently attack the
      eldest female helpers [Snowdon et al., American Journal of Primatology 31:11-21,
      1993]. Sometimes this aggression leads to the eviction of the eldest daughters
      from their natal groups 3-4 months after the birth of infants [Price & McGrew,
      Folia Primatologica 57:16-27, 1991]. We propose that daughters, during the act of
      carrying infants, may receive less aggression from mothers than when they are not
      carrying. On the other hand, given that mothers benefit from having others carry
      their infants, overall aggression received by female helpers from their mothers
      might be lower in those female helpers with a larger relative contribution to
      this activity. Four groups were observed during the first 9 weeks following the
      birth of infants, and aggression received was recorded for symmetrical as well as
      nonsymmetrical interactions. We found a positive correlation between contribution
      to infant carrying of female helpers and the overall aggression received from
      their mothers. Furthermore, the two eldest daughters with highest values of
      carrying contribution were evicted from their natal groups 3-4 months after the
      birth of infants. Although mothers do not appear to be more tolerant of female
      helpers that contribute the most to infant carrying, daughters do benefit from
      reduced aggression during the act of carrying, and remain in their natal group
      during the time period when infants must be carried.

PMID- 11977155
TI  - Bone morphogenetic proteins with some comments on fibrodysplasia ossificans
      progressiva and NOGGIN.

PMID- 11977156
TI  - Confirmation of existence of a new syndrome: LAPS syndrome.
AB  - In l998, Hopkin et al. described a new disorder characterized by progressive
      laryngotracheal stenosis, short stature, and arthropathy. We provide extensive
      clinical information on two additional unrelated patients with this distinctive
      disorder and propose the name LAPS syndrome, to reflect the most consistently
      recognized features, namely, Laryngotracheal stenosis, Arthropathy, Prognathism,
      and Short stature.

PMID- 11977157
TI  - Growth and maturation in Marfan syndrome.
AB  - Understanding the growth pattern in Marfan syndrome is important for prediction
      of expected growth, prevention of excessive growth by hormone therapy, timing of
      surgical epiphysiodesis for cessation of growth, and instituting brace treatment
      for scoliosis. In this study, we analyze growth patterns and generate growth
      charts for persons with Marfan syndrome. From the charts of 180 clinically
      diagnosed Marfan patients, longitudinal height and weight measurements were
      obtained. From this data, growth charts and growth velocity charts were generated
      for males and females. Skeletal maturation was studied by determining the Risser
      signs from the x-rays of 71 males and 56 females. From 22 female patients, age of
      menarche was available and retrieved either by reviewing the charts or contacting
      the patients. Mean length at birth was 53 +/- 4.4 cm for males and 52.5 +/- 3.5
      cm for females. Mean final height was 191.3 +/- 9 cm for males and 175.4 +/- 8.2
      cm for females. Mean birth weight was 3.51 +/- 0.74 kg for males and 3.48 +/-
      0.68 kg for females. The puberty-associated peak in growth velocity was 2.4 years
      earlier than the gender-matched general population for males with Marfan syndrome
      and 2.2 years earlier for females. Age of menarche was 11.7 +/- 2 years of age,
      which is also early compared to the general population. This study suggests that
      the growth spurt and pubertal skeletal maturation occur early in Marfan syndrome.
      The growth curves generated should help more accurately predict adult stature, as
      well as monitor progression toward it.

PMID- 11977159
TI  - No evidence for submicroscopic 22qter deletions in patients with features
      suggestive for Angelman syndrome.
AB  - Patients with monosomy 22q13.3 --> qter have, in addition to (usually severe)
      developmental delay, hypotonia, severe expressive language delay leading to
      absence of speech, pervasive developmental abnormalities, and subtle facial
      anomalies. Thus far, it has been one of the more common submicroscopic telomere
      deletions seen in patients with mental retardation. Due to the phenotypic overlap
      between monosomy 22q13.3 and Angelman syndrome (AS), 44 patients with AS features
      but without one of the characteristic molecular 15q abnormalities were tested for
      22qter deletions. In the study group, 31/44 (70%) were heterozygous for locus
      D22S163 with probe cMS607 (distance 0.125 Mb from telomere). The remaining 13/44
      (30%) patients were heterozygous for one or more of four microsatellite markers
      centromeric from D22S163 in the 22qter region (distances 1.5-4.3 Mb from
      telomere). Based on the present study, there is no evidence that patients with an
      "Angelman-like" phenotype are more likely to have a 22qter deletion than other
      individuals with mental retardation.

PMID- 11977160
TI  - Refinement of the genomic structure of STX1A and mutation analysis in nondeletion
      Williams syndrome patients.
AB  - Williams syndrome (WS) is a contiguous gene deletion disorder in which the
      commonly deleted region contains at least 17 genes. One of these genes, Syntaxin
      1A (STX1A), codes for a protein that is highly expressed in the nervous system
      and is essential for the docking of synaptic vesicles with the presynaptic plasma
      membrane. In this study, we refine the complete genomic structure of the human
      STX1A gene by direct sequencing and primer walking of bacterial artificial
      chromosome (BAC) clones and show that STX1A contains at least 10 exons and 9
      introns. The length of exons range from 27 bp to 138 bp and all splice sites
      conform to the GT-AG rule. Investigation of the STX1A gene sequence in five WS
      patients without detectable deletions did not identify any point mutations.
      Although the regulatory elements that control STX1A transcription were not
      examined, these results do not support a role for STX1A in the WS phenotype.

PMID- 11977161
TI  - Two cases with partial trisomy 9p: molecular cytogenetic characterization and
      clinical follow-up.
AB  - This paper describes two patients with partial trisomy 9p and partial trisomy 14q
      due to 3:1 segregation from de novo maternal reciprocal translocations. The
      breakpoints are different from previously described 9;14 translocations and their
      3:1 segregation products. The clinical phenotype of both cases is compatible with
      the partial trisomy 9p syndrome. We present the follow-up of both patients from
      birth up to age 7 years. Partial trisomy 9p is a frequently described chromosome
      abnormality. This does not appear to be related to a breakage sensitive locus on
      chromosome 9p, since the trisomic fragments of the published cases are
      heterogeneous. In the two cases described here, GTG-banded karyotyping suggested
      that the 9p breakpoints were similar; DNA marker analysis, however, showed them
      to be different. Such DNA studies will be necessary to define the genotype
      phenotype relation in partial trisomy 9p syndrome.

PMID- 11977162
TI  - Molecular cytogenetic characterization of a subtle interstitial
      del(3)(p25.3p26.2) in a patient with deletion 3p syndrome.
AB  - Deletion 3p syndrome is associated with characteristic facial features, growth
      failure, and mental retardation. Typically, individuals with deletion 3p syndrome
      have terminal deletions that result in loss of material from 3p25 to 3pter. We
      present a child with a clinical phenotype consistent with deletion 3p syndrome
      (ptosis, microcephaly, growth retardation, and developmental delay) and a subtle
      interstitial deletion in the distal portion of the short arm of chromosome 3,
      del(3)(p25.3p26.2). Fluorescence in situ hybridization (FISH) studies using 3p
      subtelomeric probes confirmed the terminal region of chromosome 3 was present.
      Sequence tagged sites (STS)-linked BAC clones mapping to chromosomal region 3p25
      p26 were used to characterize the interstitial deletion by FISH. The results
      indicate the deletion is within a region of approximately 4.5 Mb between STS
      markers D3S3630 and D3S1304. This interstitial deletion lies within all
      previously reported terminal deletions in deletion 3p syndrome individuals, and
      represents the smallest reported deletion associated with deletion 3p syndrome.
      Characterization of the deletion may help identify genes important to growth and
      development that contribute to the deletion 3p syndrome phenotype when present in
      a hemizygous state.

PMID- 11977163
TI  - Cerebro-osseous-digital syndrome: four new cases of a lethal skeletal dysplasia-
      distinct from Neu-Laxova Syndrome.
AB  - Neu-Laxova Syndrome (NLS) is a severe disorder with intrauterine growth
      retardation, edema, and characteristic face (including microcephaly with receding
      forehead, protuberant eyes, a flattened nose, deformed ears, cleft palate, and
      micrognathia). Ichthyosis is often present. Limb anomalies include hypoplastic
      fingers and syndactyly of fingers and toes. Patients are usually stillborn or die
      shortly after birth. We report five unrelated patients--four with atypical NLS
      and one with typical NLS. All five patients were stillbirths. Clinically, the
      atypical NLS patients showed a large skull; rhizo-, meso-, and acromelia; and
      hypoplasia of the metacarpals and phalanges. The feet were similarly affected.
      Radiographically, the atypical patients showed interpediculate narrowing and
      hypoplastic vertebral bodies. The long bones were stick-like, showing diaphyseal
      widening that spared the metaphyses and was more pronounced in the lower
      extremities. The ilia had a half-moon configuration with widening of the
      sacrosciatic notches. The ischia were vertical and the pubic bone was absent. The
      typical NLS patient showed microcephaly, normal vertebral body, and long bone
      ossification, but a pelvic configuration similar to that of the atypical NLS
      patients. The common and distinguishing clinical and radiographic features are
      reviewed. Scott et al. [1981: Am J Med Genet 9:165-175] described two patients
      with NLS with radiographic and clinical findings similar to patients 1-4 reported
      here. Patients 1-4 of this report lack the typical findings of NLS and likely
      represent a distinct lethal skeletal dysplasia.

PMID- 11977164
TI  - Duplication of chromosome region (16)(p11.2 --> p12.1) in a mother and daughter
      with mild mental retardation.
AB  - We report a 40-year-old female with mild mental retardation and behavior problems
      and her 6-year-old daughter. Chromosome analysis showed that both patients had a
      proximal duplication in the short arm of chromosome 16. The aberration was
      characterized further with band-specific probes, resulting in a 46,XX,dir
      dup(16)(pter --> p11.2::p12.1 --> qter) karyotype. The clinical and cytogenetical
      findings are compared to other patients with partial trisomy 16p reported in the
      literature.

PMID- 11977165
TI  - Subtelomeric translocations are not a frequent cause of recurrent miscarriages.

PMID- 11977166
TI  - Documentary and artistic evidence for conjoined twins from sixteenth century
      England.
AB  - Our knowledge of disease in earlier Britain is largely based on the study of
      skeletal remains. However, a series of sixteenth century illustrative ballads
      provides the first proof for conjoined twins from late medieval England. The
      dearth of archaeological cases may be due to lack of definite skeletal changes or
      as a result of the remains being denied burial within consecrated ground. Other
      cases may exist, but documentary evidence is biased to the later medieval period,
      when such birth defects were recorded solely as a warning against immorality. The
      famous Biddenden Maids, no doubt, are remembered because of their association
      with a bequest of land and distribution to the poor.

PMID- 11977168
TI  - Reported noggin mutations are PCR errors.

PMID- 11977169
TI  - Significant difference of opinion regarding the role of noggin in fibrodysplasia
      ossificans progressiva.

PMID- 11977173
TI  - Performance of cochlear implant recipients with GJB2-related deafness.
AB  - Congenital profound hearing loss affects 0.05-0.1% of children and has many
      causes, some of which are associated with cognitive delay. For prelingually
      deafened cochlear implant recipients, the etiology of deafness is usually
      unknown. Mutations in GJB2 have been established as the most common cause of
      heritable deafness in the United States. In this report, we identify cochlear
      implant recipients with GJB2-related deafness and examine the performance of
      these individuals. Cochlear implant recipients received a battery of perceptive,
      cognitive, and reading tests. Neither subjects nor examiners knew the etiology of
      deafness in these individuals. The implant recipients were then examined for
      mutations in GJB2 using an allele-specific polymerase chain reaction assay,
      single-strand conformation polymorphism analysis, and direct sequencing. GJB2
      mutations were the leading cause of congenital deafness among the cochlear
      implant recipients screened. Cochlear implant recipients with GJB2-related
      deafness read within one standard deviation of hearing controls better than other
      congenitally deaf cochlear implant recipients and non-cochlear implant
      recipients. Individuals with congenital deafness should be offered GJB2
      screening. Positive results establish an etiologic diagnosis and provide
      prognostic, genetic, and therapeutic information. Effective rehabilitation for
      profoundly deaf individuals with GJB2-related deafness is possible through
      cochlear implantation.

PMID- 11977174
TI  - Decisions about amniocentesis by advanced maternal age patients following
      maternal serum screening may not always correlate clinically with screening
      results: need for improvement in informed consent process.
AB  - We evaluated the prenatal diagnosis utilization patterns of advanced maternal age
      (AMA) patients who underwent serum screening to assess how screening results
      correlated with their decisions regarding amniocentesis. A 6-year review (1994
      1999) of laboratory records identified 2,456 AMA patients who underwent multiple
      marker serum screening. The relationship between screening results and patients'
      decisions on whether or not to undergo amniocentesis was assessed. Among the 841
      AMA patients with positive screens, more than half (52%) declined amniocentesis.
      Of the 1,615 patients with negative serum screening results, 208 (13%) opted for
      amniocentesis. We concluded that decisions by AMA patients regarding
      amniocentesis may not always correlate clinically with maternal serum screening
      results. Possible explanations, including how the state of informed consent may
      or may not contribute to these decisions, are discussed. It is suggested that
      understanding the reasons for these decisions may identify opportunities for
      improving service delivery to all pregnant patients considering prenatal testing.
      Use of a questionnaire is proposed as one mechanism for gaining a clearer
      understanding of the possible factors contributing to AMA patient decisions.

PMID- 11977175
TI  - Molecular basis of autosomal recessive diseases among the Palestinian Arabs.
AB  - In the review of the literature, 71 different autosomal recessive diseases have
      been delineated that are relatively frequent among Palestinian Arabs. Among
      those, in 40 the mutation(s) responsible for the diseases are known. Fourteen of
      these disorders were caused by a single mutation, while the other 26 were due to
      multiple mutations. Most of the mutations were found in homozygosity among the
      affected patients. It is probable that the high frequency of most of the genetic
      diseases among the Palestinian Arabs is due to a founder effect as the result of
      the high consanguinity rates in this population. However, in some cases the high
      frequency was demonstrated to be secondary to the presence of multiple mutations,
      either allelic or in different genes in a small geographic region. This
      phenomenon remains unexplained but may be secondary to a selective advantage to
      the carriers, either specific to the region or to the population.

PMID- 11977176
TI  - Clinical and genetic variability of glycogen storage disease type IIIa: seven
      novel AGL gene mutations in the Mediterranean area.
AB  - Deficiency of amylo-1,6-glucosidase, 4-alpha-glucanotransferase enzyme (AGL or
      glycogen debrancher enzyme) is responsible for glycogen storage disease type III,
      a rare autosomal recessive disorder of glycogen metabolism. The AGL gene is
      located on chromosome 1p21, and contains 35 exons translated in a monomeric
      protein product. The disease has recognized clinical and biochemical
      heterogeneity, reflecting the genotype-phenotype heterogeneity among different
      subjects. The clinical manifestations of GSD III are represented by hepatomegaly,
      hypoglycemia, hyperlipidemia, short stature and, in a number of subjects,
      cardiomyopathy and myopathy. In this article, we discuss the genotypic-phenotypic
      heterogeneity of GSD III by the molecular characterization of mutations
      responsible for the disease on a collection of 18 independent alleles from the
      Mediterranean area. We identified by heteroduplex band shift, DNA direct
      sequencing, and restriction analysis, seven novel mutations (four nonsense point
      mutations: R34X, S530X, R1218X, W1398X; two microinsertions: 1072insT and
      4724insAA; and one bp deletion: 676DeltaG), together with two new cases carrying
      a IVS21 + 1 G --> A splicing site mutation previously described in Italian
      patients. Altogether, 15 alleles were characterized. The correlation between type
      of mutation and clinical severity was studied in six patients in whom both
      mutated alleles were detected. Our data confirm the extreme genetic heterogeneity
      of this disease, thus precluding a strategy of mutation finding based on
      screening of recurrent common mutations.

PMID- 11977177
TI  - Segregation analysis of Parkinson disease revealing evidence for a major
      causative gene.
AB  - The role of genetics in Parkinson disease (PD) continues to be an area of
      considerable interest and controversy. We collected information involving the
      nuclear families of 948 consecutively ascertained PD index cases from the
      University of Virginia (UVA) Health System, the University of Medicine and
      Dentistry of New Jersey-Robert Wood Johnson (RWJ) School of Medicine, and Boston
      University (BU) School of Medicine. We performed a segregation analysis to assess
      evidence for the presence of a Mendelian pattern of familial transmission. The
      proportion of male (60.4%) and female (39.6%) cases, the mean age of onset (57.7
      years), and the proportion of affected fathers (4.7%), mothers (6.6%), brothers
      (2.9%), and sisters (3.2%) were similar across the three sites. While most of the
      index cases were male, modestly more of the reported affected relatives were
      female. These analyses support the presence of a rare major Mendelian gene for PD
      in both the age-of-onset and susceptibility model. The age-of-onset model
      provides evidence for a gene that influences age-dependent penetrance of PD,
      influencing age of onset rather than susceptibility. We also found evidence for a
      Mendelian gene influencing susceptibility to the disease. It is not evident
      whether these two analyses are modeling the same gene or different genes with
      different effects on PD. The finding of significant genes influencing penetrance
      for PD raises the question of whether these may interact with environmental
      factors or other genes to increase the risk for PD. Such gene environment
      interactions, involving reduced penetrance in PD, may explain the low concordance
      rates among monozygotic twins for this disease.

PMID- 11977178
TI  - Familial Mediterranean fever: the segregation of four different mutations in 13
      individuals from one inbred family: genotype-phenotype correlation and
      intrafamilial variability.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disease
      characterized by recurring attacks of fever and serositis. Six sequence
      alterations (M694V, V726A, K695R, M680I, M694I, and E148Q), in the MEFV gene,
      account for the majority of FMF chromosomes. Differences in the clinical
      expression have been mainly attributed to MEFV allelic heterogeneity. Homozygotes
      for the M694V mutation have a more severe form of the disease and more frequently
      demonstrate articular and renal complications. The clinical manifestations
      associated with mutation M680I are considered less severe. Mutations E148Q, K695R
      and V726A have reduced penetrance, and many individual homozygotes or compound
      heterozygotes for these mutations remain asymptomatic. Here we report on one
      inbred family with 13 individuals (one grandparent, three parents, and nine
      grandchildren), either homozygotes or compound heterozygotes, for one or two of
      four mutations (V726A, M694V, M680I, and K695R). Three parents and one
      grandparent who each carried two mutated alleles remained asymptomatic. Of nine
      grandchildren who were compound heterozygotes for two mutations in the MEFV gene,
      only those with either the M694V/V726A or the M694V/M680I genotypes manifested
      the disease, bearing further evidence to the severity of mutation M694V in
      individuals sharing a similar genetic and environmental background. Nevertheless,
      one father and one grandmother who carried the M694V/V726A compound heterozygous
      genotype were symptom-free, while the four grandchildren with the same genotype
      manifested the disease from early age, providing further evidence for the role of
      additional environmental and genetic modifiers. The occurrence of four different
      mutations in two sets of consanguineous parents merits consideration per se.

PMID- 11977179
TI  - ABCB6 (MTABC3) excluded as the causative gene for the growth retardation syndrome
      with aminoaciduria, cholestasis, iron overload, and lactacidosis.
AB  - GRACILE syndrome (growth retardation, aminoaciduria, cholestasis, iron overload,
      lactacidosis, and early death; OMIM 603358) is a rare metabolic disorder with
      autosomal recessive mode of inheritance. So far it has been diagnosed only in
      patients with Finnish ancestors. The GRACILE locus has been positioned to a
      restricted region of chromosome 2q33-37, but the causative gene remains to be
      identified. The ABCB6 gene, involved in iron homeostasis, mitochondrial
      respiratory function, and maintenance of the stability of mitochondrial DNA, has
      been positioned to this same chromosomal region, and advocated in literature as a
      highly probable candidate gene for the syndrome on both functional and positional
      grounds. We carried out sequence and quantitative expression analyses to detect
      potential disease-associated mutations in the ABCB6 gene. No mutations in the
      coding region of ABCB6 were found, and the expression level of ABCB6 in patient
      fibroblasts was found to be comparable to controls. Haplotype analysis of the
      critical DNA region provided evidence for positional exclusion also. Based on
      these data, ABCB6 is not the causative gene for GRACILE syndrome.

PMID- 11977180
TI  - Patient with the mesomelic dysplasia, Nievergelt syndrome, and cerebellovermian
      agenesis and cataracts.
AB  - We describe a 33-day-old boy who had short and thick tibiae, symmetrical
      oligosyndactyly of the hands, and distinctive face. The patient was considered as
      a case of Nievergelt syndrome, a rare form of mesomelic dysplasia. Besides the
      characteristic mesomelic limb anomalies of Nievergelt syndrome, this patient
      exhibited two additional features: agenesis of the cerebellar vermis and
      cataracts, both of which have not been previously reported.

PMID- 11977181
TI  - Further clinical and sensorial delineation of Schinzel-Giedion syndrome: report
      of two cases.
AB  - Schinzel-Giedion syndrome is a rare multiple congenital malformation syndrome
      defined by an evocative midfacial retraction, kidney and urinary malformations
      and multiple skeletal abnormalities associated to a recently described
      neurodegenerative process. Two children with SGS are reported with identical
      clinical findings: megacalycosis, progressive neurodegeneration with infantile
      spasms and hypsarrhymtic activity. Ocular investigations revealed alacrimia and
      corneal hypoesthesia. Computed tomography of the temporal bone showed a tuning
      fork malformation of the stapes for both children. These features may contribute
      to further delineation of SGS as additional clinical criteria.

PMID- 11977182
TI  - Saethre-Chotzen syndrome: notable intrafamilial phenotypic variability in a large
      family with Q28X TWIST mutation.
AB  - Saethre-Chotzen syndrome is an autosomal dominant disease characterized by
      craniosynostosis, ptosis, and limb and external ear abnormalities. Variable
      expressivity is a well-known phenomenon in this disorder. A large Indian family
      has been recently identified as carrying a nonsense TWIST mutation (Q28 X) in 17
      members, of whom 16 were examined in detail. Only 4 (25%) of the patients showed
      patent craniostenosis, namely, oxycephaly. The penetrance of craniosynostosis in
      this family is lower than previously reported in the literature. Fifteen patients
      (93%) had moderate to severe ptosis. Minor limb and external ear abnormalities
      were present in most patients. Eyelid features were the hallmark of the disease
      for 12 members of the family, suggesting that mutations in TWIST may lead to a
      phenotype with mainly palpebral features and no craniostenosis. The clinical
      analysis of this large family clearly illustrates the significant variable
      expressivity, probably related to haploinsufficiency because of the TWIST
      mutation. This phenotypic variability remains unclear but could be the result of
      modifier genes and/or genetic background effect, as noticed previously in the
      transgenic twist-null heterozygous mice.

PMID- 11977183
TI  - A rec(4) dup 4p inherited from a maternal inv(4)(p15q35): case report and review.
AB  - A rec(4) dup 4p inherited from a maternal inv(4)(p15q35) was detected in a four
      year-old girl with malformations, developmental delay, and behavioral problems
      that resemble those for trisomy 4p. A review of eight other liveborns with rec(4)
      dup 4p shows that about 40% of them also have manifestations in common with
      trisomy 4p, but the rest have a variable spectrum of malformations. Overall, the
      rec(4) dup 4p phenotype is not specific, and a diagnosis would not have been
      feasible without cytogenetic studies. This lack of a clinically recognizable
      phenotype could reflect the effects of the variable sizes of deletions of 4q,
      molecular differences in the break points, or the known variable expression of
      trisomy 4p. The fact that 79% of the recombinants in the offspring of inv(4)(p13
      p15q35) carriers are rec(4) dup 4p suggests that meiotic recombination favors its
      generation or that rec(4) dup 4q are more lethal in utero.

PMID- 11977184
TI  - Two further patients with a precocious type of osteodysplasia.

PMID- 11977185
TI  - Refinement and delineation of the breakpoint regions of a chromosome 1;22
      translocation in a patient with Costello syndrome.

PMID- 11977186
TI  - Adjunct diagnostic test for Angelman syndrome: the tuning fork response.

PMID- 11977187
TI  - Parent of a child with Down syndrome.

PMID- 11977188
TI  - Genetic drift. Your father and I.

PMID- 11977189
TI  - Comment on SMN2 deletion in childhood-onset spinal muscular atrophy.

PMID- 11977193
TI  - Advances in microanatomy of cells and tissues, biophysical and biochemical
      correlates. Proceeding of XV Congress of the International Federation of
      Associations of Anatomists and 4th International Malpighi Symposium. September 11
      16, 1999. Rome, Italy.

PMID- 11977191
TI  - SMN2 deletion in childhood-onset spinal muscular atrophy.

PMID- 11977195
TI  - Bullies and their victims.

PMID- 11977194
TI  - Alzheimer's disease: recent progress and prospects--Part II.

PMID- 11977196
TI  - The sleepy teenager.

PMID- 11977197
TI  - Heroin addicts in the long run.

PMID- 11977198
TI  - proceedings of the 12th hGH Symposium. June 17-18, 2001. Keystone.

PMID- 11977199
TI  - Enhancing drug discovery and development. Proceedings of the Lake Tahoe Molecular
      Diversity Symposia. January 29-February 2, 2001. Lake Tahoe, USA.

PMID- 11977200
TI  - 1998 Membership Directory.

PMID- 11977201
TI  - Abstracts of the 11th Annual Meeting of the British Association for Peadiatric
      Otorhinolaryngology (BAPO). September 14, 2001. Glasgow, United Kingdom.

PMID- 11977216
TI  - Survivor or weakest link? A reader shares the ups and downs of trying to return
      to his "pre-AIDS" life.

PMID- 11977217
TI  - Thoughts about having AIDS. "Being empowered by AIDS means learning the power of
      freedom, acceptance, honesty, and the value of time".

PMID- 11977215
TI  - [Doctors from the Berlin Heart Center receive the DMW Walter Siegenthaler Prize
      for 2002].

PMID- 11977219
TI  - Meanwhile, in the Poconos... Preventing HIV in the Delaware Water Gap.

PMID- 11977218
TI  - HIV prevention: ain't no mountain high enough. The Catskill Rural AIDS Services
      Education Program.

PMID- 11977220
TI  - Spiritual maturity: stories and reflections for the ongoing journey of the
      spirit.

PMID- 11977221
TI  - Reports from the National HIV Prevention Conference. August 12-15, 2001.

PMID- 11977222
TI  - D for "diagnosis" or for "denial"? Coming to grips with being newly diagnosed.

PMID- 11977223
TI  - Hysterectomy. Benefits and alternatives.

PMID- 11977224
TI  - Health tips. Removing a foreign body from your eye.

PMID- 11977225
TI  - Supplements may slow age-related macular degeneration.

PMID- 11977226
TI  - Osteoporosis is an emerging problem in men.

PMID- 11977228
TI  - Bipolar disorder. Extreme mood swings.

PMID- 11977227
TI  - Shoulder pain. Identifying, treating the problem.

PMID- 11977229
TI  - Herb quiz. Test your knowledge of over-the-counter herbal supplements.

PMID- 11977230
TI  - Second opinion. I think my husband is colorblind. What causes this condition? Is
      there a way to test for it?

PMID- 11977231
TI  - Second opinion. I'm a relatively healthy 67-year-old man. In recent months I've
      noticed an increase in the size of my breasts. What could be causing this and
      should I be concerned?

PMID- 11977232
TI  - Food packaging: ensuring the safety and quality of foods. 2nd International
      Symposium organized by International Life Sciences Institute. November 8-10,
      2000. Vienna, Austria.

PMID- 11977233
TI  - Massive pneumoperitoneum secondary to right hemidiaphragm rupture.

PMID- 11977234
TI  - Herniation of transverse colon into parietal wall after blunt trauma.

PMID- 11977235
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States, 2001-02 season.

PMID- 11977236
TI  - From the Centers for Disease Control and Prevention. Alcohol use among women of
      childbearing age--United States, 1991-1999.

PMID- 11977237
TI  - From the Centers for Disease Control and Prevention. Populations receiving
      optionally fluoridated public drinking water--United States, 2000.

PMID- 11977238
TI  - Atropine vs patching for treatment of amblyopia in children.

PMID- 11977239
TI  - JAMA patient page. Home health care.

PMID- 11977240
TI  - Identification of a new alternative-splicing transcript of Rabaptin-5 interacting
      with protein kinase MAK-V.

PMID- 11977241
TI  - Biochemical mineralization of native gold.

PMID- 11977242
TI  - Analysis of T-DNA insertion sites in transgenic tobacco plants with mutant
      phenotype.

PMID- 11977243
TI  - Substrate defense effect: the action of organophosphorus inhibitors of different
      structure on cholinesterases of various animals in the presence of different
      substrates.

PMID- 11977244
TI  - Identification and analysis of a new methylation-specific DNA-binding protein in
      mice.

PMID- 11977245
TI  - On the hormonal regulation of ovary development in wheat Triticum aestivum.

PMID- 11977246
TI  - Inhibitor specificity of cholinesterases from optical ganglia of squids of family
      Gonatidae.

PMID- 11977247
TI  - Hormonal regulation of lectin content in wheat-sprout roots.

PMID- 11977248
TI  - Ethylene as a mediator of the pollen-tube growth in the sporophyte pistil tissues
      of self-compatible and self-incompatible Petunia clones.

PMID- 11977249
TI  - Kinetics of interactions between DNA and topoisomerase II in the presence of
      physiologically active effectors.

PMID- 11977250
TI  - Immunogenic and allergenic properties of fulleren conjugates with aminoacids and
      proteins.

PMID- 11977252
TI  - [Regional meeting of the Japanese Association for Thoracic Surgery. Japan. 2001.
      Abstracts].

PMID- 11977251
TI  - Pulsed electron double resonance of spin-labeled peptides: data on the peptide
      chain secondary structure.

PMID- 11977253
TI  - Global voices on HIV/AIDS. We all have AIDS.

PMID- 11977254
TI  - Global voices on HIV/AIDS. Pasteurised human breast milk should be considered.

PMID- 11977255
TI  - Global voices on HIV/AIDS. Heterosexual transmission of HIV in Africa is no
      higher than anywhere else.

PMID- 11977256
TI  - Global voices on HIV/AIDS.  Important facts about global fund were missed.

PMID- 11977257
TI  - Cancer isn't the only malignant disease. Competent, compassionate terminal care
      should be given to everyone.

PMID- 11977258
TI  - Cancer isn't the only malignant disease. Terminal care should be discussed well
      in advance.

PMID- 11977259
TI  - Effect of retroactive intercessory prayer. Paper proves power of statistics, not
      prayer.

PMID- 11977260
TI  - Effect of retroactive intercessory prayer. "You cannae break the laws of physics,
      Captain.".

PMID- 11977261
TI  - Effect of retroactive intercessory prayer. Hope should never be squashed by being
      told that things cannot happen.

PMID- 11977262
TI  - Effect of retroactive intercessory prayer. All randomised controlled trials
      require informed consent.

PMID- 11977263
TI  - Effect of retroactive intercessory prayer. Competing interests on religious
      conviction or spirituality may be important.

PMID- 11977264
TI  - Effect of retroactive intercessory prayer. Correspondents showed misapprehension
      of principle.

PMID- 11977265
TI  - Effect of retroactive intercessory prayer. Outcome of this experiment offers
      little comfort.

PMID- 11977266
TI  - Prisoners at Guantanamo Bay. Lice get everywhere.

PMID- 11977267
TI  - Prescription drug access: not just a Medicare problem.
AB  - While all state Medicaid programs provide outpatient prescription drug coverage,
      slightly more than one in four Medicaid patients ages 18-64 could not afford to
      fill at least one prescription in the last year, according to a new study by the
      Center for Studying Health System Change (HSC). A similar percentage of uninsured
      adults also had difficulty affording prescription medications. Faced with rapidly
      rising drug spending, many states have moved to control Medicaid prescription
      drug spending by imposing copayments, limiting the number of prescriptions and
      using other cost-containment methods. The study indicates that these state cost
      control measures are contributing to Medicaid beneficiaries' prescription drug
      access problems. State and federal policy makers should keep in mind that the
      impact of these controls on Medicaid beneficiaries is likely to be greater than
      on privately insured people, given their higher need and lower incomes.

PMID- 11977268
TI  - The prevention of motion sickness in orbital flight.
AB  - A question has arisen whether zero gravity qualifies as just another "motion
      environment" in which motion sickness may be elicited, or if one or more
      undetermined etiological factors are present which render such terms as "motion
      environment" and "motion sickness" inappropriate. The question is of more than
      academic interest for the reason that in the forthcoming Shuttle Program we have
      either one problem or two: one if we are concerned solely with prevention, but
      two if we must tackle the problem of covert etiological factors as well. This
      problem points up the need to define motion sickness if investigators, world
      wide, hope to resolve the matter in the most economical manner. Meanwhile,
      substantial reliance must be placed on the use of antimotion sickness drugs and
      some recent findings are presented based on tests carried out in a rotating room
      using a new procedure. Whereas previous findings in our laboratory dealt with
      group responses, the new findings are not only valid for a group, but also valid
      for each subject tested. It was demonstrated that the effects of a drug may be
      efficacious for a group yet may be detrimental for one or more individuals in
      that group.

PMID- 11977269
TI  - Mineral and nitrogen metabolic studies on Skylab flights and comparison with
      effects of earth long-term recumbency.
AB  - A metabolic study of the effects of space flight on various chemical elements,
      particularly those with special relevance to the musculo-skeletal system, was
      carried out on the nine astronauts who participated in the three Skylab flights
      of 28, 59 and 84 days in 1973-1974. The study required of the cooperating crewmen
      constant dietary intake, continuous 24-hour urine collections and total fecal
      collections for 21-31 days before each flight, throughout each flight and for 17
      18 days post-flight. Increases in urinary calcium and negative calcium balances
      during space flight were generally similar to those found in previous
      immobilization and bedrest studies. The persistence of these alterations in
      calcium metabolism throughout the flights suggested that calcium losses would
      continue in weightlessness for a very long time. Significant losses of nitrogen
      and phosphorus occurred, associated with observed reduction in muscle tissue.
      Both mineral and muscle losses occurred despite vigorous exercise regimens in
      flight. It was concluded that unless protective measures can be developed,
      capable musculo-skeletal function is likely to be impaired in space flights,
      ultimately to be conducted to Mars, of 11/2 to 3 years duration.

PMID- 11977270
TI  - Human tolerance to acceleration after exposure to weightlessness.
AB  - The major role in the genesis of varying human tolerance to decelerations that
      follow weightlessness is evidently played by hypodynamic and hydrostatic factors.
      Long disuse of compensatory antigravity mechanisms in weightlessness may bring
      about their deconditioning and reduction of their functional capabilities, and
      may finally affect general tolerance of crewmembers to decelerations. Laboratory
      experiments demonstrated changes in the human tolerance to Gx accelerations of
      varying duration (from 3 to 100 days) and tested the efficacy of different
      countermeasures. A decrease in the human tolerance to +Gx is on the average 
      2.0g. It should be noted that an elongation of simulated weightlessness (from 7
      to 100 days) caused no further decrease in the +Gx tolerance. Our investigations
      helped to assess the threshold of human tolerance to accelerations after an
      exposure to simulated weightlessness and to delineate the value of real risk. The
      tolerance limit to +Gx accelerations which followed simulated weightlessness of
      the above duration ranged from 9.5 to 13.0g, averaging 11.6 +/- 1.6g. The
      information on the tolerance of Soviet and American astronauts to decelerations
      shown during re-entry in real space flights give support to the laboratory
      results and predictions.

PMID- 11977271
TI  - On the mechanisms of changes in skeletal muscles in the weightless environment.
AB  - Some characteristics of muscle contraction and mechanical properties of two
      muscles (M. soleus and M. extensor digitorum longus) in Wistar rats after 22 days
      of weightlessness have been investigated. On the second day after return to
      earth, the following changes were evident: slowing of twitch responses of the
      muscles studied; shortening half tetanic contraction time (defined by point of
      interactions of the increasing curve with 50% level of the peak value) in soleus;
      a rise of tension in both muscles as shown by the curve "length-force"; an
      increase of twitch/tetanus ratio and fatigability in both muscles. During
      repeated study of muscle properties, on the 26th day after return to earth, there
      were not any significant changes in values of most the above mentioned indices
      except the diminished strength of soleus. Shortening of contraction time in slow
      antigravitary soleus muscle is believed to be a sign of adaptive change in its
      characteristics resulting from unloading under the conditioning of
      weightlessness. Increased stiffness and diminished strength of muscles are
      considered as functional signs of atrophic processes, developing in the
      experiment. Dynamics of functional changes, conditioned, as we believe, mainly by
      weightlessness and correlated with morphological and biochemical data obtained on
      analogous material, allows us to postulate a reversible character of the changes
      described.

PMID- 11977272
TI  - Results of medical investigations carried out on board the Salyut orbital
      stations.
AB  - The purpose of the medical investigations carried out in flights of the Soviet
      orbital station Salyut were: to further studies and clarification of the
      phenomenology and mechanisms of changes in the main functions of the human body
      during prolonged weightlessness; to accumulate additional data on human responses
      at an early stage of adaptation to weightlessness; to assess the effectiveness of
      countermeasures against adverse effects of weightlessness during and after
      flight. The orbital station was equipped with a set of countermeasuring devices:
      a trainer for physical exercises (a treadmill), gravity simulation suit for long
      wear, bicycle ergometer, anti-G suit to be worn immediately post-flight, drugs,
      etc. The system of medical control included daily recordings of
      electrocardiography and respiration and regular physical examinations using
      provocative tests (physical exercises of a known force, lower-body negative
      pressure). Specific biomedical investigations were performed before, during and
      after flight. As in previous flights, the atmosphere in the habitable modules was
      similar to that on the earth. Food supply met the requirements for basic
      nutrients and satisfied individual preferences of the crew members. In addition
      to the time required to fulfil the flight programme, the work-rest schedule
      allowed the cosmonauts 8 hours sleep, four meals, 2.5 hours physical training and
      personal time. The biomedical investigations carried out during and after flight
      furnished information towards a better understanding of human responses to the
      effects of space flight factors and the mechanisms underlying their development.

PMID- 11977273
TI  - Irradiation of bio-objects aboard the Cosmos 690 biosatellite.
AB  - Animals on the Cosmos 690 were exposed to Cs 137 gamma-radiation of 320 curies.
      The on board emitter was a spherical container made of tungsten alloy with a
      gamma source placed in the centre. A special dose filter provided a uniform +/
      10% distribution of the dose field. Animal containers were equipped with
      thermoluminescent dosimeters. Radiation was monitored by an on-board dosimeter
      and displayed. The emitter was controlled by commands from the ground. On the
      tenth flight day the emitter was turned on and bio-objects were exposed for 24
      hours. The dose received by bio-objects located in different areas of the
      biosatellite varied from 200 to 1000 rad. The flight experiment confirmed
      entirely the reliability of the radiation system.

PMID- 11977274
TI  - Investigation of radiation sensitivity in mammals under long duration
      weightlessness.
AB  - Preliminary results of the radiobiological experiments carried out on the
      biosatellite Cosmos 690 with a radiation exposure unit on board are presented.
      The duration of the satellite flight was 20.5 days. On the tenth day of the
      flight 35 rats were exposed on board the satellite to 220 or 800 rads of gamma
      radiation. Comparison of data obtained in test and control groups of animals has
      shown that under the influence of space flight factors a somewhat more severe
      radiation injury develops than in on-ground conditions.

PMID- 11977275
TI  - Effect of irradiation in the space environment on the blood-forming system in
      rats.
AB  - A special experiment was carried out on board Cosmos 690 [correction of 605] in
      order to study the modifying influence of weightlessness on the radiobiological
      effect. On the tenth flight day 35 rats were exposed to irradiation using an on
      board gamma-ray source. They were irradiated for 24 hours at a dose rate of 32
      rads/hr with a total dose of 220 +/- 25 rads and 800 +/- 53 rads. On the 1st and
      26th post-flight days haemopoiesis in bone marrow (determined from myelograms and
      the total count of myelo-karyocytes) was examined and the blood composition was
      analysed. The total count of thymocytes and spleenocytes was measured in the
      thymus and spleen. Identical measurements were made in the control animals
      exposed to irradiation on the earth. The haematological findings indicate an
      enhancement of the radiobiological effect in the rats irradiated in space flight.

PMID- 11977276
TI  - Biochemical changes in rats flown on board the Cosmos 690 biosatellite.
AB  - Male rats of the Wistar strain were examined one day and 26 days after the 20-day
      space flight on board the Cosmos 690 biosatellite. On the 10th flight day the
      animals were exposed to 24-hour gamma irradiation: some animals were irradiated
      at a dose of 220 rad and the others at a dose of 800 rad. The data were compared
      with the results obtained from two control groups one day and 26 days after the
      experiment: (i) rats kept in the vivarium and fed with a special diet, and (ii)
      rats from a synchronous experiment (which simulated the flight profile with the
      exception only of weightlessness). The studies showed the following changes one
      day after flight: an increase in the concentration of total cholesterol, glucose,
      urea and corticosterone in the blood plasma, an increase in the concentration of
      triglycerides in the plasma, liver and bone marrow, a decrease in the
      concentration of total cholesterol in the adrenals, a reduction in the DNA and
      RNA content in the spleen and bone marrow, a decline in the potassium
      concentration together with an increase in the sodium concentration in soleus
      muscle. The degree and pattern of the changes depended largely on the dose of
      irradiation. The parameters returned to normal 26 days post-flight.

PMID- 11977277
TI  - Cytogenetic analysis of seeds of Crepis capillaris (L) Wallr. exposed on board
      the earth artificial satellite Cosmos 613.
AB  - We studied the effect of space flight factors on air-dry seeds of Crepis
      capillaris (L) Wallr. and on radiation injury of seeds exposed to gamma-radiation
      (3 kr, 525 r/min) before and after the flight on the satellite Cosmos 613. Space
      flight factors induced little increase (which was statistically insignificant) in
      the rate of chromosome aberrations in cells of the root meristem of Crepis
      capillaris sprouts, but they enhanced the effect of preliminary irradiation of
      seeds and decreased their radiosensitivity. The modification of radiation injury
      was statistically significant.

PMID- 11977278
TI  - Study with a multi-threshold HZE-particle dosimeter using plastic detectors.
AB  - During the Apollo 16 and 17 missions two units of the Biostack experiment were
      exposed to cosmic radiation. In this experiment plastic detector sheets were used
      for recording and tracing the heavy ions. In some of these sheets the integral
      energy loss spectrum was measured. The measurements were performed in two
      different cellulose nitrate materials and in Lexan polycarbonate under 4 g cm-2
      and 20 g cm-2 absorber thickness. The individual materials have different energy
      loss thresholds for the registration of heavy ions. The measured number of
      particles per cm2 with an restricted energy loss REL greater than REL0, follows a
      power law a REL(b) with b= -2.18 +/- 0.1 while the value of a depends on the
      exposure time and the absorber thickness. Calculations show that more than 70% of
      the fluence in the measured REL region is coming from particles with Z> or =20.

PMID- 11977279
TI  - Lesional effects of primary cosmic heavy ions on rat brain.
AB  - Heavy ions were detected with nuclear emulsions plates fixed on the skulls of 20
      rats which were exposed to cosmic rays at an altitude of 32,000 metres. Eight
      cases are described of correlations between ions tracks and brain lesions. The
      passage of heavy ions seems to cause functional rather than destructive
      alterations in the cells. The metabolic disturbances give a dark aspect to the
      neurons. The lesions generally appear in wide areas around the track and this
      fact suggests a physiopathological phenomenon of amplification. An evaluation of
      this biological hazard during flights of long duration at high altitude will be
      possible when the mechanism of action of heavy ions on nervous tissue is better
      known, and particularly if experiments carried out in accelerators confirm the
      small number of results obtained in flight.

PMID- 11977280
TI  - Amino acid spectrum of human blood plasma during space flight and in
      antiorthostatic hypokinesia.
AB  - The paper summarizes results of experiments on the influence of space flight and
      anti-orthostatic hypokinesia on the amino acids spectrum of human blood plasma.
      Our findings give evidence for: (i) A specific norm of the content of free amino
      acids in plasma during training and (ii) consistent changes of plasma aminograms
      during space flight related to its duration and to individual features of
      cosmonauts. The content of free amino acids in the plasma of bed-rested subjects
      varied phasically and tended to increase practically at every experimental stage.
      The paper discusses the findings and possible mechanisms of the detected changes.

PMID- 11977281
TI  - Space flight effect upon the bioenergetics of the skeletal muscles in rats.
AB  - Studies of tissue bioenergetics are very important to gain insight into the
      effects of weightlessness on the animal and human body. A reduction of the
      muscular load in zero gravity should affect reactions of biological oxidation
      because their pattern and level are related to energy requirements of the body.
      After the 22-day flight of the Cosmos 605 biosatellite tissue respiration and
      oxidative phosphorylation (P/O coefficient) in skeletal muscles of rats was
      investigated. The investigations showed that on the 2nd post-flight day oxidation
      assimilation by the muscle tissue was reduced compared with the control. In
      addition, the intensity of phosphorylation which determines the rate of ATP
      formation was decreased. These changes may reduce significantly the energy
      potential of the muscle cell and seem to form the basis for the functional
      inadequacy of skeletal muscles which can be found in men during the first post
      flight days. At later stages (the 26th post-flight day) oxygen consumption and
      phosphorylation rate increased and reached the control level. Therefore,
      readaptation to the earth gravity is followed by adaptive changes in the
      processes responsible for the accumulation and utilization of the energy of
      biological oxidation.

PMID- 11977282
TI  - Body composition changes in men and women after 2-3 weeks of bed rest.
AB  - Several parameters of body composition were measured in eight men before and
      after 14 days of continuous recumbency, and in eight women before and after 17
      days of recumbency. The parameters measured included body weight, body water,
      body potassium, plasma volume, and plasma protein concentrations. From these,
      values were derived for body fat content, lean body mass, body cell mass, and
      circulating plasma proteins. In general, the men and women responded similarly to
      continuous recumbency. Characteristically, there was significant reduction of
      plasma volume and body potassium in both groups. The women showed a significant
      reduction in circulating plasma protein, entirely in the albumin fraction; a
      similar change was observed in the men. The women, but not the men, showed a
      significant increase in circulating fibrinogen. Both men and women lost body cell
      mass, while body fat content remained the same or tended to increase slightly. It
      is expected that similar changes would occur in weightlessness. It is further
      concluded that women should tolerate the weightlessness of space flight
      physiologically as well as men.

PMID- 11977283
TI  - Deconditioning during prolonged immersion and possible countermeasures.
AB  - Test subjects covered with a waterproof highly elastic cloth were exposed to 13
      day water immersion up to the neck. They were divided into two groups. The first
      (control) group consisting of six persons was exposed to immersion alone and the
      second (experimental) group was exposed daily to accelerations of 0.6-2 Gz for 60
      90 min during the last 6 days of immersion. Before and after immersion all the
      test subjects were exposed to +3 Gz for 5 min which served as a provocative test.
      These experiments give evidence that the use of dry immersion allows
      experimentation during prolonged immersion without concomitant complications.
      Variations in the physiological parameters (cardiovascular system, fluid
      electrolyte balance, blood-coagulatory system) are indicative of the preventive
      effect of periodic accelerations during 13-day immersion.

PMID- 11977284
TI  - Biomedical results of the Skylab Program.
AB  - Skylab, the fourth in a logical sequence of USA manned space flight projects
      following Mercury, Gemini and Apollo, presented life scientists with their first
      opportunity for an in-depth study of man's response to the space environment.
      Extensive medical investigations were undertaken to increase our understanding of
      man's adaptation to the space environment and his readaptation to gravity upon
      return to earth. The flight durations of the three Skylab missions were
      progressively increased from 28 days to 59 days and, finally, 84 days. The
      results of these investigations of the various body systems clearly demonstrated
      that man can adapt to zero gravity and perform useful work during long-duration
      space flight. However, definite changes (some unexpected) in the vestibular,
      cardiovascular, musculo-skeletal, renal and electrolyte areas were documented.
      The most significant were: the occurrence of space motion sickness early in the
      missions; diminished orthostatic tolerance, both in-flight and post-flight;
      moderate losses of calcium, phosphorus and nitrogen; and decreased tolerance for
      exercise post-flight. The mechanisms responsible for these physiological
      responses must be understood and, if necessary, effective countermeasures
      developed before man can endure unlimited exposure to space flight.

PMID- 11977285
TI  - Life sciences and space research XIV. Proceedings of the Open Meeting of the
      Working Group on Space Biology of the Eighteenth Plenary Meeting of COSPAR,
      Varna, Bulgaria-29 May-7 June 1975 and Symposium on Gravitational Physiology,
      Varna, Bulgaria-30 and 31 May 1975.

PMID- 11977286
TI  - Cardiac output during physical exercises following real and simulated space
      flight.
AB  - During moderate physical work (after 5 min) the cardiac stroke volume in the
      cosmonauts who made 2--8-day flights in the Soyuz spacecraft was lower and the
      pulse rate was higher than the pre-flight level. By the end of the 49-day bed
      rest experiment the stroke volume during physical exercises (after 5 min) was
      lower than at the 5th min of the pre-test period in both the supine and sitting
      positions. The cosmonauts performed physical exercises in the sitting position.
      Therefore, it can be assumed that the major factor changing cardiac output may be
      the effect of the earth's gravity against the background of decreased orthostatic
      tolerance. Results of simulated experiments give evidence that in both cases one
      of the major factors responsible for changes in the cardiac output was a decline
      in the contractile capacity of the myocardium.

PMID- 11977288
TI  - A study of the cumulative effects of repeated exposures to radial accelerations.
AB  - After exposure to transverse accelerations of 4-10 g changes in the vascular
      system of the eye and immunobiological resistance of the body persisted from 5 to
      15 days. The data give evidence that the state of retinal vessels is the most
      informative index of the cumulative effect on the body and its recovery.

PMID- 11977287
TI  - Hypergravitation and sympatho-adrenergic reactivity.
AB  - The sympatho-adrenergic reaction of the organism subjected to hypergravitation
      was investigated in rats exposed to +6 Gz. The electro- and cardiotachograms
      recorded telemetrically were correlated with the adrenal catecholamine content.
      The determinations were made in controls and in rats treated with hexamethonium
      and atropine administered separately or together. The rats reacted to
      acceleration initially by a short bradycardia followed by tachycardia. In one
      case there was a sustained bradycardic response. Hexamethonium (C6) lowered the
      resting heart rate, attenuated the initial bradycardia and reduced the
      consecutive tachycardia. In some rats during centrifugation a bradycardic and
      arhythmic response was found sometimes ending in cardiac arrest. Hexamethonium
      stored the catecholamines in the adrenals as a result of their increased
      concentration. Atropin brought about resting tachycardia, disappearance of
      bradycardia from the very beginning of centrifugation and a more accentuated
      tachycardia. Atropin and hexamethonium administrated together diminished the
      response to acceleration.

PMID- 11977289
TI  - Effect of space factors on Escherichia coli B/r cells.
AB  - Stationary phase cells of Escherichia coli B/r were inactivated when they were
      exposed to high vacuum (10(-6) torr). About 5% of the cells were still able to
      form a colony after 45 min exposure. Vacuum dried cells (0.5 torr, 120 min) show
      colony forming ability of 30% or more. They were inactivated to about 5% by
      further vacuum treatment. Vacuum treated cells showed higher permeability for
      various cell components. UV irradiated E. coli B/r cells in vacuum showed
      increased UV sensitivity. DNA-protein cross-links were preferentially formed in a
      vacuum. To obtain 63% of DNA cross linked with protein required 852 erg mm-2
      (D37) of UV irradiation in suspension and only 72 erg mm-2 of UV irradiation in
      vacuum. The protein components of DNA-protein cross-links were hydrolysed with
      pronase E and the amino acids directly bonding to DNA were determined. The most
      important amino acids concerned in DNA-protein cross-links seem to be glycine and
      alanine, followed by aspartic acid (asparagine), glutamic acid (glutamine) and
      histidine. The sensitivity to X-rays of stationary phase E. coli B/r cells seems
      to depend on the remaining gas atmospheric in the vacuum since it varies with
      different pumping systems.

PMID- 11977290
TI  - Weight and shape.
AB  - In his Discorsi of 1638, Galileo argued that large terrestrial vertebrates would
      have to grow very thick legs in order to avoid the decreasing cross-sectional
      area/weight ratios of large objects geometrically similar to small prototypes.
      Since then, scaling theory (especially the principle of decreasing relative
      surface area in large forms) has been one of the most widely appreciated and,
      paradoxically, least studied areas of biology. The two major themes of scaling
      theory have been: (1) That small and large animals live in different adaptive
      "worlds" regulated by forces dominant at their size (surface forces for insects,
      gravity for large organisms). These forces place limits on the size of organic
      designs (breathing through external tracheae and presence of exoskeleton
      constrain insects to be small; buckling strength limits the height of trees;
      scaling of kinetic energy at something close to l(5) sets maximum height of
      terrestrial bipeds). (2) That small and large animals have characteristic
      differences in form and function conditioned by the scaling of surfaces and
      volumes (large animals have relatively smaller brains, thicker legs, lower
      metabolism, longer life, more convoluted internal surfaces for gas exchange,
      digestion and circulation). We know that organic form is adapted to body size,
      but a major issue for space research involves the degree of purely genetic
      determination for such adaptation. If, as D'Arcy Thompson argued for the
      trabeculae of the human femur, adaptations to large size require the immediate
      action of gravitational forces, then prolonged weightless flight will provoke
      reversion by removal of the necessary stimulus. In any case, we must know what
      scaling theory predicts (and what animals actually display) in order to predict
      the potential problems of prolonged weightlessness.

PMID- 11977291
TI  - Gravity and embryonic development.
AB  - The relationship between the developing embryo (both plant and animal) and a
      gravitational field has long been contemplated. The difficulty in designing
      critical experiments on the surface of the earth because of its background of 1
      g, has been an obstacle to a resolution of the problem. Biological responses to
      gravity (particularly in plants) are obvious in many cases; however, the
      influence of gravity as an environmental input to the developing embryo is not as
      obvious and has proven to be extremely difficult to define. In spite of this,
      over the years numerous attempts have been made using a variety of embryonic
      materials to come to grips with the role of gravity in development. Three
      research tools are available: the centrifuge, the clinostat, and the orbiting
      spacecraft. Experimental results are now available from all three sources. Some
      tenuous conclusions are drawn, and an attempt at a unifying theory on
      gravitational influence on embryonic development is made.

PMID- 11977292
TI  - Physiological effects of sustained acceleration.
AB  - A review is given of the literature concerning the physiological and
      pathophysiological changes in humans, caused by sustained acceleration. After
      definition of the acting forces and an introduction into terminology, circulatory
      and respiratory mechanisms are described which are active under sustained
      acceleration. The origin of visual disturbances associated with acceleration is
      discussed. Acceleration tolerance is influenced by magnitude, duration,
      direction, and rate of application of G-forces together with environmental
      conditions and the condition of the subject. Acceleration protection may be
      achieved by technical devices (anti-g suits), voluntary manoeuvres and change of
      posture. Recent work dealing with high sustained +Gz (HSG) is reviewed and the
      associated problems are discussed.

PMID- 11977293
TI  - Physiological changes associated with long-term increases in acceleration.
AB  - The long-term retention of organisms in increased acceleration fields is an
      experimental approach towards understanding the biological consequences of earth
      gravity. Such treatment, called chronic acceleration, simulates a change in
      gravity and requires exposed organisms to adapt physiologically to the new
      environment. Information from chronic acceleration supplements that from space
      physiology in understanding gravitational physiology. Many of the responses in
      long-term exposure to increased acceleration are those which would be anticipated
      from the imposed symmetrical loading. For example, increased requirements for
      posture and locomotion induce appropriate changes in musculo-skeletal organs.
      Displacement of body fluids and increased hydrostatic pressures lead to greater
      blood volumes and increased tissue hydration. However, there are also specific
      acceleration effects which cannot be so directly interpreted. Among these are
      decreases of mature body size and of depot fat, which are proportional in degree
      to field strength. The role of chronic acceleration research in the development
      of gravitational biology and its relationship to earth-orbital experiments are
      considered. The applicability of chronic acceleration studies with human subjects
      towards planning of deep space exploration is also discussed.

PMID- 11977294
TI  - The influence of glucose-insulin-kalium mixture (GIK) on the selected parameters
      of acid-base balance in acute myocardial infarction.
AB  - The aim of the paper was assessing the influence of polarizing GIK mixture on the
      selected indicators of acid-base equilibrium in patients with acute myocardial
      infarction treated fibrinolytically. The patients had arterial blood taken in
      order to check pH, partial pressure of oxygen and carbon dioxide, and the content
      of bicarbonates. Changes in the examined parameters in the group obtaining GIK
      and in the one obtaining placebo were subject to critical analysis. Changes in
      gasometric parameters taking place under the influence of GIK administered to
      patients were also analysed according to the site of infarction. It was observed
      that after 24 hours from the beginning of infusion pH increased and pCO2
      decreased in comparison to the initial examination. These changes did not depend
      on the kind of applied infusion (GIK or physiological saline infusion), no
      significant changes in bicarbonates being observed. However, after applying GIK
      infusion, an increase in oxygen pressure in comparison with the control group was
      observed, and differences between the groups were within the boundaries of
      significance. Neither was there observed any influence of infarction site on
      changes in the assessed parameters of acid-base equilibrium in the group treated
      with GIK nor in the one receiving placebo.

PMID- 11977295
TI  - Imaging diagnostic approach to tumours of ramus and angle of the mandible.
AB  - The abundance of up-to-date diagnostic equipment and imaging techniques makes it
      necessary to reconsider diagnostic approach to many maxillofacial disorders,
      including mandibular tumours, and to elaborate algorithms of radiological
      examinations allowing for the planning of a cost-effective treatment based on
      thorough diagnostics. The material was composed of 146 case records of 68
      patients examined in the years 1995-2000 in the Medical University of Lublin.
      There were selected radiograms as well as the results of other imaging modalities
      of persons with clinically confirmed tumours of mandibular ramus or angle. In
      each case there were noted: the initial and the final diagnosis as well as the
      number and sequence of the performed diagnostic examinations. On the basis of the
      obtained results there was proposed a diagnostic algorithm in cases of mandibular
      angle and ramus tumours, which was presented in the form of a scheme. It was
      proved that conventional radiograms are still fundamental in initial selection of
      patients while other diagnostic imaging methods are indispensable in treatment
      planning.

PMID- 11977296
TI  - The application of digital radiography and radiodensitometry in evaluation of
      chronic fibrous periapical changes of endodontically untreated teeth.
AB  - Lesions in hard tissues of teeth can be detected on radiograms only when there
      exists considerable decrease in mineralisation. By means of digital radiography
      the diagnostics of dental pathologies becomes more precise and objective. The aim
      of the paper was the radiodensitometric evaluation of chronic fibrous periapical
      changes. The material comprised 308 digital intraoral radiograms of teeth with
      periapical changes among which there were chosen the cases of clinically
      confirmed chronic fibrous periapical inflammations of endodontically untreated
      teeth. All radiograms were analysed in the Digora Soredex digital radiography
      system in gray scale, in full colour and using the tomosynthesis function. The
      linear measurements of root densities were carried out at the distance of 1 mm
      from radiological apices while the measurements of alveolar bone at the distance
      of 2 mm from it. Twenty-five teeth without evident periapical changes formed the
      control group. There were found significantly lower densities of roots and
      alveolar bone in the group of chronic fibrous periapical lesions in comparison
      with the control group. A characteristic feature of chronic fibrous periapical
      changes is the density of the root of an affected tooth that is higher than in
      acute inflammation and at the same time lower than in the control group. The
      radiodensitometry proved to be useful in evaluation of chronic fibrous periapical
      changes.

PMID- 11977297
TI  - Early detection of potential impaction of permanent maxillary canines caused by
      resorption disorders of deciduous canines.
AB  - Maxillary canine impaction is an often-encountered dental anomaly as after the
      third molar it is the maxillary canine that is the most frequently impacted
      tooth. One of many factors causing impaction of maxillary canines is the presence
      of the persistent primary canine. The aim of the study was early evaluation of
      resorption of deciduous maxillary canines and an attempt at prediction of
      impaction or delayed eruption of their permanent counterparts as well as the
      possibility of their eruption in proper position in the dental arch. There were
      examined digital intraoral radiograms of 43 patients at the age from 8 to 11
      years (44% boys, 56% girls). All the radiograms were taken using the Digora
      Soredex digital radiography system. There was observed the presence and degree of
      resorption of deciduous maxillary canines according to age and sex. It was
      evaluated whether a deciduous canine might be a mechanical obstacle for erupting
      the permanent tooth. It was concluded that although physiological resorption of
      deciduous maxillary canine begins at the age of 8, it is radiologically evident
      on intraoral digital X-rays taken at the age of 9-10 years. So the best time to
      assess a patient for potential resorption of primary canine and possibilities of
      eruption of its equivalent in proper position in dental arch is between the 9th
      and 10th year of age.

PMID- 11977298
TI  - Evaluation of mandibular bone structure with radio-visiographic method--its
      usefulness for diagnostic purposes.
AB  - The noninvasive assessment of the mandible bone structure can be, beside the
      indices of mineral density and content of mineral elements, the source of
      valuable information of diagnostic and prognostic importance. The presented
      examinations aimed at working out a computer program of radiovisiographic picture
      analysis of the mandible bone, which, on the basis of radiological trabecula
      algorithm, would enable finding out parameters determining mean number of
      trabeculas per 1 mm2 of the analysed area, density expressed in percentage of the
      area covered with trabeculas, mean width and height of radiological trabeculas,
      and several calculable derivative indices. On the basis of the above mentioned
      program there was made an analysis of radiovisiograms of 130 patients with
      diagnosed osteoporosis and of 110 patients without osteoporosis, treated in the
      Department and Clinic of Dental and Maxillofacial Surgery, Medical University of
      Lublin. Slight differences conditioned by sex and age of the patients as well as
      significant changes in structural indices in patients with generalized
      osteoporosis were found. The performed tests show that standardized
      radiovisiographic examinations of mandibular bones completed with computer
      structure analysis by Radiograph Workshop program can be helpful in diagnostic of
      osseous changes in mandibular bones.

PMID- 11977299
TI  - Histological changes in placenta villi in some types of pathological pregnancy.
AB  - The examinations were carried out on 3 placentas from normal pregnancies and 12
      placentas from pathological pregnancies (gestosis, cholestasis, type A diabetes
      pregnancies and premature outflow of amniotic fluids). Placenta sections were
      fixed in glutaraldehyde and subsequently embedded in Epon 812. Semithin sections
      1 mu thick were stained with methylene blue and azure. Moreover, changes in
      terminal villi were assessed. In comparison with the control placentas changes in
      blood vessels, stroma and syncytiotrophoblast were found.

PMID- 11977300
TI  - Ultrastructural changes in the syncytiotrophoblast in some types of pathological
      pregnancy.
AB  - The studies were performed on 12 placentas from pathological pregnancies
      (gestosis, cholestasis, type A diabetes pregnancies, premature outflow of
      amniotic fluids) and 3 placentas from normal pregnancies. Ultrathin sections were
      stained by the Reynold's method and evaluated under the electron microscope BS
      500 (Tesla). The changes found in syncytiotrophoblast were the following: the
      increase or the decrease in its thickness, increase in basal membrane thickness,
      decrease in the number or lack of pinocytic vesicles and superficial microvilli,
      damage of mitochondria.

PMID- 11977301
TI  - The evaluation of noise level in different points of urban area.
AB  - The aim of the study was measuring noise intensity in the selected points of
      traffic routes in the city of Lublin. Investigations were carried out at 11
      points located in the centre of the city and at escape roads. Noise value levels
      showed variable intensity, the highest being observed in the morning and
      afternoon hours. The highest mean level of noise intensity was recorded at the
      crossing of Solidarnosci Avenue and Sikorskiego Street, and the lowest in
      Narutowicza Street.

PMID- 11977302
TI  - Clinical and radiological aspects of Kartagener's syndrome.
AB  - The paper presents the picture of Kartagener's syndrome in a 14-year-old in whom
      inversed position od the vicera ectases of the bronchi and inflammatory changes
      in maxillary sinuses were found. Recurrent infections of the respiratory system
      should suggest changes of this type of etiology requiring USG examinations of
      internal organs and especially CT of the lungs.

PMID- 11977303
TI  - HRCT examinations in the course of silicosis.
AB  - Evaluation of diagnostic possibilities of high definition computerized tomography
      was performed on the material of 38 patients with recognized silicosis of small
      opacities on the bases of long lasting exposition, clinical and radiographic
      picture. Special usefulness of HRCT was shown in revealing early, scanty,
      radiographically imperceptible nodular changes. The presence of the so-called air
      traps was shown on expiratory sections.

PMID- 11977305
TI  - Histoclinic of the abdominal aortic aneurysms.
AB  - The aim of this study was to analyze the scientific protocol of 21 patients
      operated due to abdominal aortic aneurysm. Arterial hypertension was the common
      feature for the whole group. Typical microscopic changes for true aortic aneurysm
      in all histopathological findings were approved. A different in size thrombus was
      always present inside the aortic sac. In every case atherosclerotic lesions were
      recognized in the aneurysm wall. In some samples the multiple inflammatory
      infiltration consisting of mononuclear cells were observed. Simultaneously an
      intensive angiogenesis process was seen.

PMID- 11977304
TI  - Activity of Tumor Necrosis Factor-alfa (TNF-alpha) and selected acute phase
      proteins in plasma of psoriatic patients receiving local treatment.
AB  - Plasma concentrations of Tumor Necrosis Factor-alpha (TNF-alpha), C-reactive
      protein (CRP) and alpha-2 macroglobulin (alpha-2 MG) were examined in 100
      patients with medium-severe and severe psoriasis. Activity of selected proteins
      were measured using the ELISA method in the active stage of psoriasis and in
      remission achieved due to the local treatment with 0.125-2% dithranol treatment.
      In the active stage of disease highly increased plasma levels of TNF-alpha, CRP
      and alpha-2 MG were found (p < 0.001) and remission was connected with a
      considerable decrease of the examined proteins towards the control values. But
      despite its lowering, CRP mean plasma level remained in remission significantly
      elevated in comparison with healthy control. Results of this study indicate that
      in severe psoriasis the acute phase response can be initiated and is not
      completely extinguished with achievement of clinical remission.

PMID- 11977306
TI  - Excess male mortality at the productive age in Poland at the end of the 20th
      century.
AB  - In the last decades of the 20th century there was observed a continuous increase
      in mortality rates of men at the productive age, which still causes enormous
      economic and social problems. Thus the aim of the paper is the analysis of the
      causes of excess death rates in men at the productive age in Poland. There were
      gathered demographic data collected by the Main Statistical Office (GUS)
      concerning Polish society as well as available epidemiological data related to
      the state of health of male population in Poland. The mortality rates referring
      to Polish males were analysed in several age groups. It was observed that the
      main causes of excess male mortality in Poland were cardiovascular diseases,
      neoplasms as well as trauma and accidents, which is consistent with the trends in
      the whole population. The mortality rates from ischaemic heart disease and
      pulmonary cancer have doubled in the years 1970-1990. However, in the last years
      of the 20th century there is perceived a decreasing trend in mortality of men at
      the productive age. The maintenance of this trend will be very profitable for the
      Polish society in the new millennium.

PMID- 11977308
TI  - The relationship between estrogen and the development of liver vascular
      disorders.
AB  - The liver is central to the metabolic disposition of all drugs and foreign
      substance. Drug-induced liver injury is a potential complication of estrogen
      preparations. The primary estrogen-induced vascular disorders are peliosis
      hepatis and vasculitis. Peliosis hepatis has been described as a rare consequence
      of taking estrogens and contraceptive. This condition is characterized by the
      presence of blood-filled spaces. Vasculitis has been noted as necrotizing or non
      necrotizing hypersensitivity and an inflammatory infiltrate involving all the
      wall of a vessel. Vasculitis is usually connected with the presence of increased
      numbers of eosinophils either in blood or tissues. The aim of the study was to
      determine the influence of estrogen preparations on liver vascular disorders. The
      experiment was conducted on female rats of Wistar strain with the initial body
      weight of 180-300 g/kg of the body weight. After acclimation period, animals were
      gathered in 5 experimental groups of min. 10 in the group. Oestradiolum benzoicum
      was used for the purpose of this study. It was given i.m. once a week for 8 weeks
      in three different doses: E1--0.0075 g/kg, E2--0.0015 g/kg; E3--0.003 g/kg of the
      body weight. Two control groups were designed: K0--the untreated animals, K1--the
      animals receiving the adequate quantity of oleum pro injection. Fragments of
      organ assigned for histological examination were fixed in 10% buffered
      formaldehyde solution and transformed into paraffin sections. Histological
      preparations were evaluated in the light microscope. The histological assays were
      determined using: hematoxylin-eosin, azan and histochemical paS (periodic acid
      Schiff) stains. In the described experiment large inflammatory infiltrations and
      vasculitis (E2, E3) were observed. In the animals treated with higher doses of
      estrogens diffusely distributed infiltrations around spaces with bloody fluid
      inside were revealed. The lumen of vessels was dilated. Estrogens can be
      responsible for the development of vascular disorders described as peliosis
      hepatis. The observed changes were suggestive of drug related vasculitis. An
      increased awareness of peliosis hepatis may become an important symptom for a
      pathologist, especially in patients at risk.

PMID- 11977309
TI  - Free radicals-induced morphological changes in the pancreas.
AB  - Oxidative stress occurs whenever there is an imbalance between the generation of
      free radicals and the antioxidant defense. Oxygen is cytotoxic if oxygen
      concentration is higher than its amount in the atmosphere. This phenomenon is
      called hyperoxide process. This experiment was performed to determine the
      influence of normobaric hyperoxide process on peroxidation occurred in the rat's
      pancreas. Furthermore, the aim of this study was to estimate morphological
      changes in the pancreas. The studies were carried out on 44 male Wistar strain
      rats with the initial body weight of 230-250 g. After acclimation period the
      animals were divided into four experimental groups of 11 in a group. The exposure
      period of the influence of chemically pure oxygen was the base of the
      classification of rats into experimental groups labelled as follows: I, II, III.
      The time of exposure was 12, 24 and 48 hrs, respectively. The animals were
      dissected immediately after decapitation. The internal organs were investigated
      during autopsy. The whole pancreas with surrounding fatty tissue and peritoneum
      was cut out. Ultrastructural identification of different cell types required
      examination of several sections from each block and careful examination of
      numerous selected photographs. The histological preparations were evaluated in
      electron microscope. Histological evaluation revealed the presence of changes
      which seem to be adaptative and temporary. The B cells of Langerhans' islets were
      more damaged than other endocrine cells.

PMID- 11977307
TI  - Induction of metallothioneins by ethanol and morphine.
AB  - Metallothioneins take part in homeostasis of the ions of metals which are
      necessary for proper metabolism of the organism (zinc, copper), biosynthesis
      regulation and zinc proteins activity as well as in the processes of detoxication
      of cells from toxic metals. Besides, they also protect cells from the reactive
      forms of oxygen, radiation, electrophilic pharmacological agents used in the
      cancer therapy, and the mutagenes. The aim of the study was to determine the
      level of metallothioneins in tissue of rats intoxicated with ethanol and
      morphine. The experiment was to state whether the applied narcotic agents cause
      the change in the metallothionein's level in the liver, brain and kidneys of the
      intoxicated animals. The experiment was carried out on 6-month-old rats of Wistar
      strain, weighing 150-200 g, which were given ethanol intragastrically and
      morphine intraperitoneally for 5 days. The metallothioneins level in tissues was
      determined by cadmium-hemoglobin affinity assay, using the cadmium isotope (109
      Cd). It was found that the level of metallothioneins in the group of animals
      intoxicated with ethanol was elevated (in kidneys it increased 1.5 times, in the
      liver--3.5, and in the brain--10 times). In the case of morphine-intoxicated rats
      the level of metallothioneins also increased in all the examined tissues; the
      increase was fifteen-fold in the brain, threefold in the liver, and twofold in
      kidneys. It results from the above studies that the narcotic agents used for the
      animals' intoxication produce the increase in the level of metallothioneins in
      all the examined rats' tissues. The examinations prove different force of
      metallothioneins induction according to a tissue.

PMID- 11977310
TI  - Pathophysiologic role of oxygen-free radicals in toxic damage of the liver.
AB  - The role of oxidative stress in toxic injury of the liver has been well
      documented. Molecular oxygen is indispensable for most of the living organisms
      but under specific conditions can be cytotoxic for all organisms. If oxygen
      concentration will be higher than its amount in the atmosphere, different
      pathological processes can occur in aerobic organisms. In normal hepatocytes,
      this physiologic oxidant stress is easily handled by mitochondrial defense. On
      the other hand, there are a lot of clinical indications to therapeutic
      application of both normobaric and hyperbaric hyperoxide processes. This work was
      undertaken to determine the influence of normobaric hyperoxide process on
      morphological structure of rat's hepatic cells. Furthermore, the aim of this
      study was to determine the degree of dependence between the time of hyperoxide
      process and morphological changes in the liver. The experiment was conducted on
      44 male Wistar strain rats with initial body weight of 230-250 g. After
      acclimation period, the animals were gathered in experimental groups of 11 in a
      group. The exposure time of the influence of chemically pure oxygen was the base
      of the classification of rats into experimental groups labelled as follows: I,
      II, III. The time of exposure was 12, 24 and 48 hrs, respectively. The control
      groups also contained 11 animals. The animals were dissected immediately after
      decapitation. The whole liver was cut out. Fragments from the right central lobe
      and from the left lateral lobe of the liver were taken. The histological
      preparations were evaluated in electron microscope. In all the experimental
      groups adaptative and probably temporary histopathological changes were noted in
      the liver. The observed damages were probably reversible.

PMID- 11977311
TI  - The obtention of vascular access on the arm for hemodialysis.
AB  - The chronic dialysis is the way of replacing the lost kidney function. Well
      functioning vascular access is the prerequisite for chronic hemodialysis
      treatment. The arteriovenous fistulas are the optimal form of vascular access. In
      patients, in whom the usual sites for fistula have been exhausted the vascular
      fistula on the arm was placed. 53 dialysis accesses were performed on the arm
      between 1989 and 1999. All subcutaneous fistulas were created by the junction of
      the cephalic vein with brachial artery, just above the cubital fossa on the
      anterior surface of the arm. All anastomoses were created in the operating room
      under local anesthesia. The preferred route for exposure of cephalic vein was
      making the single incision along the arm. When the distal part of cephalic vein
      has been ligated and divided, the adequate space for the graft in the tunnel was
      performed. End-to-end anastomosis between the distal end of vein and side of
      brachial artery was completed using the suture material. In 50 hemodialysed
      patients the regular flow through the arteriovenous fistula was observed. Fistula
      thrombosis occurred in 2 cases. In 4 examined patients we observed blood
      extravasation in the subcutaneous tissue, where the tunnel was created. In 5
      patients the local cellulitis was noted. The late vascular complications were
      evaluated in 15 cases. Aneurysms were revealed clinically in 3 patients and false
      aneurysm occurred in 2 patients. The described late complications required no
      surgical correction. The anterior side of the arm is the best place for
      arteriovenous access used for hemodialysis, in patient without the possibilities
      of surgical creation of the forearm's fistula.

PMID- 11977312
TI  - Evaluation of serum copper (Cu) level dynamics in measles patients.
AB  - The aim of the present study was to estimate the cuprum(Cu) level in blood serum
      in patients ill from measles in the acute period of the disease and three weeks
      after regression of clinical symptoms in comparison with the control group. The
      investigations included 26 patients aged 14-34, hospitalised due to measles in
      the Department of Infectious Diseases of the Medical University of Lublin. The
      analysed group included patients without coexisting diseases, in which clinical
      improvement after the carried out treatment was obtained. All the patients had Cu
      concentration in the blood serum twice determined during hospitalisation period
      and once during the period of convalescence. The control group included 24
      healthy persons aged 15-19, who had Cu concentration in blood serum only once
      determined. The obtained in numbers data were subject to a statistical analysis.
      Both in the acute period of measles and during convalescence a statistically
      significantly higher Cu level in blood serum in comparison to the control group
      was observed.

PMID- 11977313
TI  - Estrogen-dependent activity of kidney lysosomal proteolytic enzymes.
AB  - Drug-induced kidney injury is a potential complication of a number of
      medicaments. The wide-spread use of estrogens in the form of oral contraceptives
      and in the form of hormonal replacement therapy, has necessitated extensive
      studies on the biochemical alterations. The following effects of estrogens on
      kidney are discussed in greater detail with special regard to enzyme induction.
      The aim of the study was to evaluate the influence of long-term activity
      estrogens on kidney lysosomal enzymes like cathepsin B, D and L. Female rats were
      divided randomly into eight experimental groups. Oestradiolum benzoicum was used
      for the purpose of this study. Estrogens were given i.m. one time per week for 8
      weeks in different doses, respectively: E1--0.00075 g/kg b.w., one time per week;
      E1.1--0.00075 g/kg b.w. every three days; E2--0.0015 g/kg b.w.. one time per
      week. E2.1--0.0015 g/kg b.w.. every three days; E3--0.03 g/kg b.w.. one time per
      week; E3.1--0.003 g/kg b.w.. every three days; KO--untreated animals; K1--treated
      control, rats received oleum pro injection at the dose of 1.2 ml/100 g b.w. The
      activity of free and bound fractions of lysosomal enzymes, such as cathepsin B, D
      and L were assayed in kidney homogenates using spectrophotometric methods.
      Differences between various experimental groups were tested with ANOVA test. The
      activity of cathepsin B, D and L fractions showed significant changes compared to
      control groups. The observed changes were not characteristic in all the studied
      groups. The most important changes referred to the activity of cathepsin B and D.
      Differences were noted between the enzymes activity in animals treated with the
      smallest dose of estrogen and that in control groups. It was smaller in group E1
      than in groups K0 and K1. The activity of cathepsin B was higher in group E1 than
      in control groups. There was no correlation between the dose of injected
      estrogens and the observed lysosomal activity changes. The changes in lysosomal
      activity were uncharacteristic.

PMID- 11977314
TI  - Breast cancer--the diagnostic and therapeutic problem.
AB  - The progress made in recent years in the diagnostics of breast cancer, the
      universal character of mammographic and ultrasonographic screening examinations
      and the growth of social awareness with respect to this disease have caused a
      great deal of diagnostic problems. Cases of big, ulcerating cancer tumours, which
      infiltrate skin have now become history, and are reported sporadically. However,
      physicians are now facing the problem, which is the diagnosis of 1-5 mm changes
      detected in examinations. The necessity to diagnose small tumours in combination
      with 80-90% mammographic sensitivity reported compelled clinical physicists to
      verify these changes with histopathological examination. In the cases when the
      clinical examination, the result of a mammographic examination and that of fine
      needle aspiration biopsy do not provide a coherent picture, a surgeon has to
      qualify a patient for tumorectomy with an intra-operative study. In the years
      1997-2000, 173 breast tumorectomies were made. Patients with benign neoplasm
      (e.g. adenofibroma, papilloma mammae) or patients with arousing suspicion of
      oncological anxiety breast tumour were qualified for surgical procedures.
      Operations were performed in one-day surgery conditions and intra-operative
      examination was performed in every case. In cases of non-palpable tumours, which
      were visible in ultrasonography or mammography the changes were marked by an
      "anchor" in order to be removed and examined histopathologically. The operated
      patients were 17-89 years old. In the obtained 173 tissue fragments dysplasia
      benign was recognized in 47.98% of cases, in 42.2% adenofibroma, in 2.31%
      papilloma mammae, in 1.73% mastitis chronica, in 4.62% ca ductale invasivum and
      in 1.16% ca ductale in situ has been observed.

PMID- 11977315
TI  - Delta aminolevulinic acid urinary excretion in rural region inhabitants.
AB  - The purpose of the work was to estimate to what extent the inhabitants of a
      typical agricultural region are exposed to the influence of lead compounds. 132
      people at the age of 9 to 74 were included in the research. Urinary delta
      aminolevulinic acid (ALA) excretion was determined. The highest excretion of ALA
      was observed among the examined who were up to 18 years old, while the lowest was
      among those who were above 60 years old. These differences, however, were not
      statistically significant.

PMID- 11977316
TI  - Vitamin E influence on selected parameters in rats after ochratoxin A
      intoxication.
AB  - The aim of the research was to evaluate vitamin E influence on ochratoxin A (OTA)
      toxicity based on analysis of selected parameters of white and red cell system in
      rats. The animals were divided into groups: I--control, II--treated with OTA, III
      -treated with OTA and vitamin E. In group II a significant decrease in the values
      of hematocrit, hemoglobin level, red and white cell counts was observed. In group
      III an average hematocrit, hemoglobin level were significantly lower than in
      control group, nevertheless they were higher than in group II.

PMID- 11977317
TI  - Expression of selected T-cell antigens in the skin infiltration in primary
      cutaneous T-cell lymphomas.
AB  - Skin biopsy specimens obtained from 16 patients with mycosis fungoides (MF) were
      examined immunohistochemically to assess phenotype of T-cells. Cases of benign
      chronic skin disorders (BCD) were included in control group. Examination of skin
      biopsies obtained from patients with MF revealed aberrant immunophenotypes of T
      cells (loss of one or more of T-cell markers CD7, CD5, CD8, and rarely CD3). The
      expression of CD1a antigen both in the dermis and epidermis of the studied groups
      was similar and normal. No correlation between this loss of antigenicity and the
      prognosis was observed. These disturbances were seen in most of the cases of the
      early MF, but not seen in inflammatory skin diseases. In conclusion, the presence
      of aberrant immunophenotype of T-cells in skin infiltration may be useful in the
      diagnosis and differentiation of MF.

PMID- 11977318
TI  - The level of magnesium in the serum of children hospitalized for severe
      respiratory infections.
AB  - The objective of the studies was evaluation of the level of magnesium in children
      hospitalized for severe respiratory infections (mainly pneumonia and bronchitis).
      The criterion for the evaluation of the magnesium level in the serum of the
      children hospitalized for severe respiratory infections were the following
      parameters: general condition of the child at the time of admittance, feeding
      pattern and psychosomatic development in the children with respiratory infection.
      The level of magnesium in the serum of the children admitted with median general
      condition was higher than that of the children admitted with poor general
      condition. The level of magnesium in the serum of breastfed children and those
      with correct psychosomatic development was higher than the level of magnesium in
      children fed artificially and representing backward psychosomatic development.

PMID- 11977319
TI  - Primary adenocarcinoma of the jejunum--a case report.
AB  - A case of adenocarcinoma of jejunum is reported. Although survival figures in
      adenocarcinoma of the small bowel appear to correlate with early presentation,
      due to poor specificity of the symptoms a preoperative diagnosis is very seldom.
      Therefore, in order to improve the treatment outcome, the diagnosis must be done
      at an early stage. Thus there are discussed imaging modalities applied in
      diagnostics of this rare pathology.

PMID- 11977321
TI  - The use of USG spatial reconstructions in diagnosing cholelithiasis and
      cholecystitis.
AB  - The aim of the paper is to determine diagnostic value of Spatial USG
      reconstructions in the diagnostics of cholelithiasis and inflammatory changes in
      the gallbladder. There was discussed the optimal way of examining the gallbladder
      in 3D USG presentation and advantages resulting from the use of the spatial
      option in diagnosing biliary deposits in selected inflammatory changes. USG
      spatial reconstructions which supplement the standard 2D USG examination in the
      diagnostics of difficult and doubtful cases of gallbladder pathology were found
      useful.

PMID- 11977320
TI  - Multiple synchronous granular cell tumours of the esophagus: a case report.
AB  - Granular cell tumours (GCTs) are relatively uncommon, usually benign and solitary
      neoplasms. Approximately 5-11% of all tumours occur in the gastrointestinal tract
      and about one third of them appear in the esophagus. Till now, only 30 cases of
      multiple esophageal GCTs have been reported in the literature. We present the
      case of a 44-year-old man with three synchronous GCTs in the distal esophagus.
      The lesions were detected incidentally during esophagoscopy. Histopathologic
      examination of tissue samples revealed the nests of polygonal cells with small
      hyperchromatic nuclei and abundant granular cytoplasm located in the lamina
      propria of the mucosa. The cytoplasmic granules were positively stained with PAS
      and were diastase resistant. The positive immunostaining for S-100 protein was
      also noted.

PMID- 11977322
TI  - Analysis of antioxidant enzyme activity and magnesium level in chronic
      obstructive pulmonary disease (COPD).
AB  - There is an increasing interest in the relationship of hypomagnesemia and
      oxidative stress in pulmonary diseases. It seems to be clinically relevant to
      assess prooxidant/antioxidant balance and its correlation with magnesium level in
      COPD. In this study, there were investigated the antioxidant enzymes activity and
      magnesium plasma level in a group of patients with chronic obstructive pulmonary
      disease and in the control group. The study group consisted of 41 patients
      admitted to hospital for ambulatory medical treatment in pulmonary department of
      the Medical University of Lublin. The control group was made up of 20 patients
      who were admitted for control examinations. Superoxide dismutase (SOD), catalase
      (CAT) and glutathione peroxidase (GPX) activity were assessed in red blood cells
      using kinetics methods. Significantly decreased activity of CAT in COPD,
      insignificantly decreased activity of GPX and insignificantly increased activity
      of SOD were detected. Patients with COPD also showed the lowered plasma magnesium
      level. The conclusion is that COPD is accompanied by a lowered magnesium level
      and an alteration in antioxidant status due to possible oxidative stress in this
      disease.

PMID- 11977323
TI  - Cardiopulmonary manifestations of subarachnoid hemorrhage--a case report.
AB  - The study presents a case of a 48-year-old female patient, in whom first symptoms
      of subarachnoid hemorrhage were suggestive of acute pulmonary oedema, caused by
      acute left ventricular insufficiency, evoked by myocardial infarction. The
      authors discuss the course of illness, diagnostic difficulties and changes in
      circulatory system, which can appear as a result of subarachnoid hemorrhage.

PMID- 11977324
TI  - Level of serum cytokines in biliary gastritis and erosive gastritis with
      Helicobacter pylori coinfection.
AB  - The aim of this study was evaluation of serum cytokines level in patients with
      biliary and erosive gastritis. 50 patients were admitted to this study: 20 with
      biliary, 20 with erosive gastritis and 10 as the control group. In all patients
      serum levels of Il-8, Il-6R, Il-2R were evaluated. In each group half patients
      were infected by Helicobacter pylori, and the second half were uninfected. Mean
      level of Il-8 in patients with biliary gastritis was higher than in those in the
      control group, and was more increased in Helicobacter pylori infected patients
      than in uninfected ones. In erosive gastritis accompanied by Helicobacter pylori
      infection mean level of Il-8 was higher than in uninfected patients for which the
      level was normal. Serum Il-6R levels in biliary gastritis with infection by
      Helicobacter pylori were higher than in biliary gastritis without infection.
      These values were statistically significant vs. the control group. In erosive
      gastritis accompanied by Helicobacter pylori mean level of Il-6R was higher than
      in the control group, but was normal in patients without Helicobacter pylori. We
      noticed no influence of Helicobacter pylori infection on Il-2R levels in patients
      with biliary gastritis and erosive gastritis. These levels were normal in all
      groups of patients. In conclusion, in biliary gastritis we found the levels of Il
      8, Il-6R higher than in erosive gastritis. Particularly significantly high levels
      of Il-8, Il-6R were observed in gastritis accompanied by Helicobacter pylori
      infection.

PMID- 11977325
TI  - The influence of the new benzodiazepine derivative BD-1158 on the behaviour of
      rabbits in spontaneous conditions.
AB  - BD-1158 is a new 1,4 benzodiazepine derivative. The purpose of the present
      experiments was to test the spontaneous behaviour (typical of a rabbit) after
      administration of BD-1158 and thus to define the activity and side effects of
      this substance under physiological conditions. The experiments were performed for
      3 subsequent days in a group of 10 rabbits. On the first day spontaneous
      behaviour was tested. On the second day 1 ml of 1% starch solution was
      administered intraperitoneally. On the third day BD-1158 was administered
      intraperitoneally at a dose 10 mg/kg diluted in 1% starch solution up to 1 ml, 35
      40 minutes before the beginning of the experiment. Six phases of behaviour were
      estimated. It was concluded that BD-1158 has a strong anxiolytic and sedative
      effect, decreases the state of animal's attention, water and food uptake.

PMID- 11977326
TI  - Possibilities of spatial imaging of carotid arteries pathologies in Power-Doppler
      US.
AB  - The aim of the study was to assess the value of Power-Doppler US spatial
      reconstructions in examining pathologies of carotid arteries for determining its
      role in the diagnostic algorithm. 3D Power-Doppler US reconstructions were
      performed in 19 patients with pathologies of carotid arteries qualified for
      surgical treatment on the basis of Color-Doppler examinations. Digital data of 2D
      US sections secondarily gave spatial pictures. Most frequently, 14 times,
      different degrees of carotid artery stenosis were found, in 3 cases critical, and
      complete impatency was observed twice. The narrowings were caused by both
      atheromas and parietal clots. In 3 cases the internal carotid artery formed an
      angular refraction. Spatial pictures also determined the geometry of division of
      common carotid arteries. It was found that Power-Doppler 3D US perspectively
      visualizes the configuration of carotid vessels and the range of their pathology
      facilitating understanding of the extent of changes and mutual topographic
      relationships. Spatial imaging let visualize atheromas and ulcerations of their
      surfaces besides the degree of carotid arteries narrowing.

PMID- 11977327
TI  - Diagnostic value of US and CT in the assessment of ovarian teratomas and their
      qualifications for surgical treatment with laparoscopic method.
AB  - In the group of 17 women after surgery with histopathologically confirmed
      diagnosis of teratomas diagnostic usefulness of US and CT was analysed.
      Differentiated echostructure of tumours was correlated with different densities
      of pathologic tissues in CT examination, also after their contrast enhancement.
      In 2 patients teratomas of both ovaries were recognised, in the remaining 15
      women tumours were unilateral. In total morphologic pictures of 19 teratomas were
      assessed, 9 times tumours with prevailing liquid component had the picture of a
      thick-walled cyst, 7 times these were hyperechogenic fatty foci and in 3 cases
      had the character of solid tumours. Teratomas had different morphologic pictures,
      but it was possible to show the prevalence of one element and classify the tumour
      to one of the three types of teratomas. It was found that US examination, due to
      its high frequency, lets early diagnose teratomas before they are accessible in
      the clinical exam, in the symptomless period or when they give indirect symptoms,
      usually dysuric ones. CT examination, due to its high sensitivity in recognising
      fatty tissue and calcifications, is necessary before laparoscopic operation
      requiring fragmentation of big tumours to determine their character.

PMID- 11977328
TI  - The influence of nifedipine (calcium channel blocker) and Bay-K-8644 (calcium
      channel agonist) on the development of experimental acute pancreatitis.
AB  - The aim of this paper was to evaluate the influence of nifedipine (calcium
      channel blocker) and Bay-K-8644 (calcium channel agonist) on cerulein acute
      pancreatitis (AP) in rats. AP was induced according to the Lampel and Kern method
      (1) by the continuous intravenous infusion of cerulein in the doses of 5 x 10(-6)
      g/kg/h for 12 hours. There was obtained a statistically significant decrease in
      serum amylase activity and pancreatic weight in the groups treated with higher
      doses of nifedipine before infusion of the cerulein compared with rats treated
      only with cerulein. However, in the group treated with Bay-K-8644 before infusion
      of cerulein statistically significant increase was obtained in serum amylase
      activity and pancreatic weight compared with the group treated only with
      cerulein. The investigations suggest a beneficial effect of higher doses of
      nifedipine on cerulein induced AP. The inflammatory changes in the pancreas in
      the groups treated with nifedipine observed under the light microscope were
      smaller than in the group treated only with cerulein.

PMID- 11977329
TI  - Method of Patient Classification System in obstetric staff scheduling. I.
      Criteria and categories of care.
AB  - The lack of verified Patient Classification System methods for obstetric care
      provided incentives for the development of own proposal, which would be adjusted
      to the conditions in Polish delivery rooms and the mothers' demand for these
      services. Four main criteria of obstetric care were adopted which corresponded to
      the subsequent stages of labour. These main criteria were ascribed more than a
      dozen detailed criteria concerning the specific character of obstetric care, as
      well as general nursing care. The chart containing the criteria of care
      facilitated the classification of women in labour into individual categories of
      obstetric care. Three categories of care were distinguished: Category I of
      minimum obstetric care, Category II of moderate obstetric care, and Category III
      of intensified obstetric care.

PMID- 11977330
TI  - Method of Patient Classification System in obstetric staff scheduling. II. Demand
      for direct nursing in the delivery room among mothers who deliver by natural
      birth.
AB  - After the development of categories and criteria of nursing mothers who give
      birth in the delivery room, the direct nursing time provided for women at
      childbirth by the midwives in individual categories of care was determined. The
      model time which should be provided for mothers according to their actual needs
      was also determined. The results of the study showed that among women who
      delivered naturally, statistically significant differences were observed between
      two variables: the nursing time provided and the model time. Hence, for women who
      deliver naturally it would be advisable that the nursing time standard for
      midwives resulted from the model times.

PMID- 11977331
TI  - Method of Patient Classification System in obstetric staff scheduling. III.
      Demand for direct nursing in the delivery room among mothers who deliver by
      Caesarean section.
AB  - In own studies concerning the determination of the demand for the direct nursing
      time in the delivery room, the mothers examined were divided into two groups:
      those who delivered naturally and those who delivered by Caesarean section. The
      results of the study showed that no statistically significant differences were
      observed between the nursing time received from midwives by the women who
      delivered by Caesarean section and the model time. Therefore, the standards
      concerning the number of nursing staff for this group of women may be determined
      based on either provided or model times.

PMID- 11977332
TI  - Special characteristics of nursing staff scheduling in intensive care units.
AB  - The method of determination of working time standards for nursing staff
      scheduling based on self-observation, which is applied in hospital practice,
      evokes doubts concerning its methodological correctness. Considering the lack of
      nursing care standards and not always optimum quality of care, this method may
      contribute to the preservation of standards which would not guarantee patients'
      safety. Therefore, studies have been undertaken to find out if there are any
      differences between the nursing time provided in intensive care units, and the
      time which patients should be provided with according to their actual demand for
      care. The study covered 63 patients in the ICU, for whom the time of performing
      2,821 various therapeutic and nursing activities was measured. In order to
      determine working time standards a more reliable method was applied--an active
      observation with time-scheduling technique and model times. Patients who differed
      with respect to the diagnosis, state of health, and period of hospitalization
      were ascribed three categories of care according to their state of health and the
      adopted criteria of care. Statistically significant differences were noted
      between the nursing time devoted to patients and the time they should be provided
      with according to their demand for care.

PMID- 11977333
TI  - The expression analysis of the estrogen and progesterone receptors in endometrial
      carcinomas.
AB  - The aim of the study was the analysis of expression of estrogen (ER) and
      progesterone (PR) receptors in endometrial carcinomas. The expression of each of
      the receptors was examined with reference to such parameters as: patients' age,
      the relation to menopause, histological type and grading, the depth of myometrial
      infiltration and the presence of endometrial hyperplasia adjacent to the tumour.
      There were found very significant correlations between the degree of histological
      grading and expression of ER and PR and between values of index ER and PR. There
      was obtained correlation between the expression and endometrial hyperplasia only
      for PR.

PMID- 11977334
TI  - The influence of prophylactic vaccination on epidemic situation of infectious
      diseases illustrated by the epidemiology of measles in Poland in the years 1968
      1998.
AB  - There were gathered demographic data collected by the Main Statistical Office
      (GUS) concerning Polish society. There were analysed the incidence, morbidity and
      mortality rates as well as the number of cases and number of deaths from measles
      in Poland in the years 1968-1998. It was stated that the introduction of
      prophylactic vaccinations against infectious diseases totally changed the
      epidemiologic situation. It was also stated that measles is a good example of the
      influence of prophylactic vaccinations on the course of disease. The measles
      vaccinations caused the elimination of periodicity of the disease, increase in
      the interepidemic periods, decrease in incidence rates and nearly eliminated
      morbidity from this disease. There is a chance of eradication of measles in
      Poland provided that mandatory vaccination periods are strictly kept and 99% of
      children at the age of two years are vaccinated.

PMID- 11977335
TI  - Evaluation of nursing care standard in a neurological ward.
AB  - Providing high quality of nursing care is extremely important with respect to the
      specific character of neurology, dealing with negative consequences of chronic
      and incurable diseases which often lead to disability. Quality in nursing denotes
      the degree of achieving the desired effects with respect to the state of health
      and health promoting attitudes. The precondition for the provision of quality is
      the development and implementation of the standards of care. The standard is an
      average typical model or pattern which is attainable and measurable, i.e. a basic
      level below which the performance is not acceptable. A standard contains the
      following criteria: structural (staff, technology, finance), process (provision
      of services), and effect measuring the effectiveness of the nursing care. The
      evaluation was conducted in the Neurology Ward at State Hospital No. 4 in Lublin
      by the assessment of the work of nurses and its effects, based on a sample of 85
      patients. Evaluation was carried out by comparing the nursing standard provided
      in practice and the theoretical standard which covered a complete realisation of
      the structural criteria and partial fulfillment of process and effect criteria.
      This resulted in the majority of patients (61.5%) obtaining optimum functional
      independence.

PMID- 11977336
TI  - Health education and radicular syndrome.
AB  - The aim of the study was to determine the level of health education among 45
      patients with radicular syndrome--21 males and 24 females aged 23-64. The level
      of health education was measured twice: prior to and after health education. At
      Stage I of the study the level of knowledge was generally low, the mean
      percentage of correct answers to all questions being 43.0%; whereas at Stage II
      this percentage was significantly higher, the level of knowledge was defined as
      satisfactory and increased by 33.4% reaching the value 76.5%. The highest level
      of knowledge was observed with respect to the principles concerning lifting and
      handling loads, as well as learning; while the lowest level--with respect to the
      correct standing position, both during the first and the second measurement
      (slightly over 50% of respondents correctly described this position.

PMID- 11977337
TI  - Neural correlates of emotions in psychiatric patients in the light of functional
      neuroimaging findings.
AB  - The question whether there exists "the emotional brain" still remains open. The
      greatest scientific challenge at the threshold of 2000 is to make "a map of brain
      emotions" with a detailed topography for each "basic emotion". The
      investigations, with the use of the most advanced neuroimaging techniques:
      positron emission tomography(PET), functional magnetic resonance (fMRI) and SPECT
      (single photon emission computed tomography), aimed at obtaining more precise
      location data on the system regulating the effect in normal and in pathology. In
      recent years, with the use of neuroimaging techniques, an important role of
      posterior temporal cortex, orbital-frontal cortex, amygdaloid nucleus and insula
      in the regulation of emotional behaviour has been indicated. The present study is
      an attempt at: 1) systemizing the research experiments serving the investigation
      of emotions with the use of neuroimaging techniques, 2) systemizing the latest
      results of investigations aimed at either search of the "emotional brain", or
      neural correlates of emotions responsible for the regulation of emotional
      behaviour in anxiety and affective disorders as well as in schizophrenic
      disorders.

PMID- 11977338
TI  - Types and patterns of contrast enhancement of hepatic tumours (hepatoma,
      hemangioma and metastasis) with dynamic computed tomography.
AB  - Dynamic sequential computed tomography (d-CT) of the liver was performed in 69
      patients with histopathologic findings of hepatoma (HCC), 62 patients with
      hemangioma and in 78 patients with proved 134 liver metastases. Dynamic
      enhancement in hepatoma, hemangioma and metastases was analysed during the
      nonequilibrium phase (30-150s) and delayed equilibrium phase (2,5-7 min) using
      the following classification of tumour: totally hyperdense, centrally hyperdense,
      mixed density, totally isodense and totally hypodense. In the early examination
      phase 14 (19%) HCC were totally hyperdense or peripherally hyperdense, and 40
      (57%) HCC were totally hypodense. In the early phase 49 (79%) hemangiomas were
      peripherally hyperdense. In the early nonequilibrium examination phase 62%
      metastases were hypodense. In the delayed phase 94% HCC were totally hypodense.
      Hemangiomas in the delayed phase were totally hyperdense and totally isodense
      (17/29). In the equilibrium examination phase 97% metastases were hypodense. The
      contrast enhancement pattern of hepatomas, hemangiomas and metastases seen in
      dynamic CT scanning is useful in diagnosis of these tumours.

PMID- 11977339
TI  - Clinical evaluation of Gabitril and Lamictal for drug-resistant epilepsy in
      adults.
AB  - Second generation antiepileptics lamotrigine (LTG) and tiagabine (TGB) were
      primarily licensed for adjunctive treatment of simple and complex partial
      seizures with/without secondary generalisation as similarly effective drugs.
      Reduction of seizures frequency is the most important index of drug efficacy, but
      overall therapeutic benefit estimated as a quality of life is nowadays the target
      goal of management. In this study efficacy and tolerability of LTG or TGB as
      short-term add-on treatment in patients with refractory complex partial seizures
      were assessed by the use of both physician-rated measures (mean monthly seizure
      frequency, responders rate, adverse events, clinical biochemistry) and patients
      perceived change in their own quality of life estimation (descriptive scale and
      visual analogue scale-VAS). Comparable efficacy of LTG (n-22, 378 mg/day) and TGB
      (n-26, 43 mg/g) was assessed as 41 and 35% of responders and above half of
      patients with noticeable improvement. 25% of patients in both groups reported
      reduction of seizures severity in 4-points descriptive scale. Biochemistry values
      did not show clinically significant changes after treatment. 13% of patients on
      LTG reported adverse events (headache, asthenia, irritability, insomnia). This
      coefficient was greater for TGB-35% (asthenia, headache, sleepiness, vertigo).
      However, no case of discontinuation as a result of adverse events was reported
      for either of the tested drugs. Even if efficacy of LTG and TGB was comparable in
      objective measurements, only patients on LTG reported a significant quality of
      life improvement in VAS. This might be the consequence of more frequent adverse
      events and treatment schedule of TGB (triple dosing/day). This trial confirmed
      that VAS might be used as an easy additional test in evaluation of antiepileptic
      drug for individual patient in everyday clinical practice.

PMID- 11977340
TI  - Acid phosphatase activity in different organs as a marker of acute pancreatitis.
AB  - The aim of the experiment was to establish and quantify the changes in the
      activity of acid phosphatase in the pancreas, liver, spleen and kidneys during
      the course of experimental pancreatitis. The experiment was carried out on 65
      male rats of Wistar strain, whose weight varied from 250 to 350 g. The animals
      were standard fed. They drank only water 24 hours before operation. The rats were
      randomly divided into three groups: A--intact animals group which were not
      operated and were used to mark initial biochemical parameters (15 rats), B--the
      experimental group of animals which were injected by retrograde way with sodium
      taurocholate into the common bile-pancreatic duct to induce acute necrotic
      pancreatitis (50 rats). After laparotomy an injection needle was inserted into
      the common bile-pancreatic duct via the proximal part of the duodenum (Aho's
      method). After 2, 6, 12, 24, 48 hours rats were anaesthetised again, and
      thoracotomy was performed by taking blood for amylase determination from the left
      ventricle of the heart. Then the animals were given an overdose of ketamine, and
      the organs were removed during laparotomy and frozen at the temp. of -20 degrees
      C. Alpha-amylase activity in the blood serum was determined by the enzymatic
      method. Acid phosphatase activity was assayed by spectrophotometric methods using
      a substrate which releases 4-methyloumbeliferol reacting with the enzyme. The
      authors concluded that the activity of membranous fraction of acid phosphatase
      changed non-specifically over the course of experimentally induced acute
      pancreatitis in rats, but statistically significant difference was found in the
      enzyme's activity during different periods of pancreatitis only in the pancreas
      and in the liver.

PMID- 11977341
TI  - Changes in glucose, cholesterol and serum lipid fraction levels in experimental
      diabetes.
AB  - The objective of this research was to trace the changes in serum glucose,
      cholesterol and lipid fractions during progression of diabetes in rabbits. 89
      male rabbits, New Zealand breed were used in the experiment. Diabetes mellitus
      was induced by a single injection of alloxan. On day 7 the glucose level in the
      whole blood was measured by a glucometer to confirm the presence of diabetes.
      From this day the time of disease was counted. The rabbits were divided into the
      following groups: Group 1--controls (n = 18), Group 2-21 days diabetes mellitus
      (n = 18), Group 3-42 days diabetes mellitus (n = 17), group 4-90 days diabetes
      mellitus (n = 19), group 5-180 days diabetes mellitus (n = 17). After above
      mentioned periods blood samples were taken and the rabbits were killed by
      decapitation. The final level of glucose in the sera was determined
      spectrophotometrically by enzymatic method. The method of cholesterol measurement
      was based on oxidation of free cholesterol to cholesterol releasing hydrogen
      peroxide. Measurement of lipid fractions was based on indirect methods consisting
      in precipitation of specific lipoprotein fractions. Control rabbits revealed
      highly significant (p < 0.01) or significant (p < 0.05) correlation between
      initial and final cholesterol and glucose levels. It was not observed in diabetic
      rabbits. Highly significant correlation (p < 0.01) was found between LDL and
      total cholesterol concentration in 21 and 42 day of diabetes. Similar correlation
      was observed between HDL and total cholesterol concentration on 90th day of the
      course of disease. We concluded that significant disorders of lipid metabolism
      occur in the course of alloxan-induced diabetes in rabbits, manifested by total
      cholesterol level increase and changes in proportions and levels of serum lipid
      fractions.

PMID- 11977342
TI  - Speech re-education in patient with motor aphasia in collaboration with family.
AB  - The presented paper is an example of family education in managing the patient
      with motor aphasia following the stroke. The neurological diagnosis confirmed a
      medium hemiparesis on the right side. During the third week following the stroke,
      the re-education of speech was taken up basing on the new style of working with
      patient, i.e. biopsychosocial model of illness and treatment. In this aspect
      patient is the subject and the therapy is addressed to the patient taking into
      account his system of values with reference to the illness. The aim of the study-
      speech therapy--was achieving a maximum integration with the society by solving
      the problem situation of a patient, i.e. the lack of verbal contact. Speech
      therapy was performed for 8 weeks and it applied pedagogic and neurolinguistic
      methods of therapy. The sessions were held every day of maximum 25 minutes. At
      the final stage of speech re-education the patient had a good verbal contact with
      the environment.

PMID- 11977343
TI  - Education on rational nutrition of elementary school children in the city of
      Lublin.
AB  - The paper presents the stages of preparation of Nursing Faculty students of the
      Medical University in Lublin for realisation of lessons popularising the
      knowledge about rational nutrition. The analysis of school documents allowed for
      selecting a group of children aged 11-13. The subjects of the lessons were
      adapted to the age and demands of the audience. The realisation of the syllabus
      was made during four meetings in three schools in Lublin. The realisation of
      dietary education confirmed poor knowledge of nutrition, too little amount of
      fruit, vegetables and dairy products in everyday menu with big amounts of
      carbohydrates and animal fat, frequent lack of second breakfast at school. The
      school, besides the family, should realise the tasks connected with the
      popularisation of healthy diet and the deficit and excess of body weight). The
      evaluation of students' educational activities indicated that more time should be
      devoted to the methodology of health education with particular attention to
      activating methods within such subjects as public health, family medicine.

PMID- 11977344
TI  - Changes in rabbits' behaviour under the influence of corticotropin derivative
      analogue 4-10 in spontaneous conditions.
AB  - The influence and the role of corticotrophin analogue 4-10 on the rabbits'
      behaviour in spontaneous conditions was analysed. The data analysis indicated
      that analogue 4-10 with modified aminoacid sequence in 8, 9, 10 positions
      significantly influenced the behavioural changes in the general model of
      behaviour. The 4-10 corticotrophin derivative caused the suppression of
      aggression, considerably reduced the tension and orientation-cognition reactions,
      however, it prolonged comfort and grooming significantly. This may prove the
      noticeable reaction of analogue 4-10 in modification of behavioural pattern,
      which was expressed by restraining the reaction of stressogenic character with
      simultaneous attenuation and prolongation of appetite reactions.

PMID- 11977345
TI  - Biochemical markers of damage of the central nervous system in multiple
      sclerosis.
AB  - The examination of biochemical markers of the damage of the central nervous
      system may be the excellent complement of the neuroimaging methods. There are
      factors in the cerebrospinal fluid which indicate the damage of the precise
      structures of the CNS. In this paper there are described the main markers which
      are used in diagnostic multiple sclerosis: myelin basic protein (MBP) as a marker
      of demyelination of the white matter, neuron specific enolase (NSE) as a marker
      of neuronal damage, tau protein, 14-3-3 protein, neurofilament protein-subunit
      light (NFL) as markers of axonal damage and S-100 protein and glial fibrillary
      acidic protein as markers of astroglial damage.

PMID- 11977346
TI  - A case of the Roussy-Levy syndrome family.
AB  - Roussy-Levy syndrome, also known as hereditary areflexic dystasia, is a very rare
      genetic neuromuscular disorder that typically becomes apparent during early
      childhood. The disorder is characterised by inherited gait ataxia, pes cavus and
      areflexia which are eventually associated with distal muscle atrophy, postural
      tremor and minor sensory loss. We report a family whose members in three
      generations (grandmother, mother, daughters) were showing these clinical signs of
      Roussy-Levy syndrome. All of these women have displayed gait ataxia, areflexia,
      pes cavus and sideways curvature of the spine (kyphoscoliosis).

PMID- 11977347
TI  - C-reactive protein (CRP) as a response to postoperative stress in laparoscopic
      cholecystectomy using the abdominal wall lift, with performed pneumoperitoneum
      (CO2), and in open cholecystectomy.
AB  - The first laparoscopic cholecystectomy was performed thirteen years ago and
      rapidly became the preferred way of operation in patients suffering from
      cholelithiasis. The pneumoperitoneum can be responsible for haemodynamic
      disorders. The abdominal wall lift is an alternative way for pneumoperitoneum
      during laparoscopic cholecystectomy. The aim of this study was the comparative
      analysis of operative trauma response in the patients treated by laparoscopic
      cholecystectomy using abdominal wall lift and in cases which underwent open
      cholecystectomy or laparoscopic operation using pneumoperitoneum. The
      concentration of C-reactive protein was measured in patient serum before and
      twice after surgery. The obtained data underwent a statistic analysis. In all
      cases the surgery caused the marked changes of CRP-concentration. The mean level
      of CRP was higher three times in patients after open cholecystectomy than in
      cases treated by laparoscopic cholecystectomy with the use of abdominal wall lift
      or with performed pneumoperitoneum. During the experiment the statistically
      significant different between laparoscopic surgery with the use of the laparolift
      and laparoscopic with earlier performed pneumoperitoneum was observed. The stress
      and inflammatory response in cholecystectomy using abdominal wall lift was
      significant but smaller than the response noted in open cholecystectomy and
      similar to the response observed after pneumoperitoneum. The replacement of
      pneumoperitoneum by abdominal wall lift does not change the operative stress in
      laparoscopic cholecystectomy.

PMID- 11977348
TI  - The secondary hemodialysis vascular access created through the basilic vein
      transition on the forearm.
AB  - Hemodialysis vascular access related problems account for most hospitalizations
      in chronic hemodialysis patients. Having exhausted classic, primary radio
      cephalic fistula on the forearm the secondary vascular access can be created. The
      secondary access was achieved through a subcutaneous displacement of the basilic
      vein and through surgical creation of end-to-end fistula between this venous and
      radial artery on the forearm. The subject of the study were eight patients
      undergoing chronic hemodialysis. In all patients the type of anastomosis and
      early and late complications were studied. The preferred route for exposure of
      the basilic vein was making the single incision along the forearm. Next, the
      basilic vein was transferred to the subcutaneous tunnel on the anterior side of
      the forearm. In four cases the classic end-to end anastomosis between the basilic
      vein and radial artery was performed. In other four patients, the telescopic
      method of fistula creation was done. In all eight cases the regular flow was
      observed. In postoperative period no complications were noted.

PMID- 11977349
TI  - Influence of salmon calcitonin on the analgesic effect of selective kappa-opioid
      agonist in mice.
AB  - In the present study the relationship between calcitonin and kappa-opioid system
      was analysed. The possibility that salmon calcitonin (S-CT) exerts analgesic
      activity in mice as well as the influence of salmon calcitonin on the analgesic
      effect of kappa-opioid agonist, U-50, 488H were examined. The writhing test in
      mice was used as analgesic test. S-CT given alone intraperitoneally at a high
      dose produced antinociceptive effect. S-CT given at a subanalgesic dose increased
      the antinociceptive effect of kappa-opioid agonist, U-50, 488H. The obtained
      results suggest that the increase in the effectiveness of kappa-opioid receptor
      agonist may be one of the mechanisms involved in the analgesia induced by salmon
      calcitonin.

PMID- 11977350
TI  - Short- and long-term results of stapedectomy in children.
AB  - Otosclerosis in children and teenagers is very uncommon. Typical otosclerosis
      presents as a slowly progressive conductive hearing loss and tinnitus in the
      third to fourth decade of life. Stapedectomy is a well-established procedure for
      correction of conductive hearing loss in adult patients with otosclerosis. The
      aim of this work is to assess short- (6 months) and long-term (7 years) results
      after stapedectomy performed in 10 patients under 20 years of age. In 1 patient
      cochlear otosclerosis was diagnosed and in 1 patient incus anomaly was found
      during the operation. Pure tone audiograms obtained 6 months after stapedectomy
      showed air-bone gap closure to 10 dB in 6 patients, to 15 dB in 8 patients and in
      all patients to 20 dB. Average air conduction threshold improved by 26.5 dB and
      average bone conduction threshold by 5.9 dB. 7 years after stapedectomy air-bone
      gap was similar to the one measured 6 months postoperatively. Stapedectomy in
      children provides good and stable hearing results.

PMID- 11977351
TI  - Nucleolar organizer regions in laryngeal cancer.
AB  - The purpose of this study was to estimate the prognostic value of the AgNORs
      count per nucleus in laryngeal cancer. The sections of diagnostic, formalin-fixed
      and paraffin-embedded specimens from 48 patients with T1-4 tumours were stained
      with silver nitrate for visualization of NORs (AgNORs). The correlation between
      AgNORs score and tumour clinicopathological features was estimated. The mean
      AgNOR number per nucleus was 2.73 +/- 0.87 (range 1.48-4.38). The AgNOR counts
      did not correlate with the stage of the disease, patient survival rate and N
      stage. A significant correlation between the mean AgNORs number and various
      stages of histological differentiation of carcinoma was observed (p < 0.05).

PMID- 11977352
TI  - Imaging diagnostics strategy in maxillary sinus neoplasms.
AB  - Malignant neoplasms of maxillary sinuses are a serious diagnostic and therapeutic
      challenge, so the objective of a clinician is the planning of a cost-effective
      strategy promptly leading to proper diagnosis and the onset of treatment. Thus
      the aim of the paper was the elaboration of diagnostic strategy in maxillary
      neoplasms. There were analyzed 163 case records of 78 patients with maxillofacial
      neoplasms. The number and sequence of the conventional radiograms as well as
      diagnostic imaging methods were registered. There was proposed an algorithm of
      application of imaging techniques in diagnostics of neoplasms of maxillary antra.
      It was found that conventional X-rays are still valuable in screening for sinus
      pathology and as indication of the necessity of performing other imaging
      examinations. Computed tomography and magnetic resonance are complementary in
      visualization of pathologic masses and bone tissue destruction.

PMID- 11977353
TI  - Long-term monotherapy with lamotrigine in newly diagnosed epilepsy in adults.
AB  - Lamotrigine (LTG) as both effective against a wide range of seizure types and
      epileptic syndromes and well tolerated drug is being used in mono--as well as in
      polytherapy of pharmacoresistant epilepsy. The aim of this study was to evaluate
      the efficacy, safety and neuropsychological functioning after LTG (mean daily
      dose: 316 mg) as long-term monotherapy (12 mo) in 24 young adult out-patients
      (22.5 ys) with newly recognised and not-previously treated epilepsy in an open,
      non-comparative trial. 67% of patients were responders (above 50% reduction in
      seizure frequency) and 42% reported seizures remission. The best were results in
      patients with generalised convulsive fits (87% with remission). Adverse events in
      the early phase of medication in 21% of patients typically concerned CNS and
      gastrointestinal system (headache, asthenia, insomnia, nausea, gastric aches) and
      resolved spontaneously without treatment discontinuation. Biochemical
      examinations were normal and transient leucopenia and diminishion of MCV were
      clinically not significant. Neurodynamic abilities, neuropsychological
      examination results, memory verbal and visual tests and organic evaluation in
      organic triada tests did not show deterioration after LTG treatment. Slight
      difficulties in abstractive and operative thinking and some focal symptoms of
      fronto-temporal origin should be considered a result of drug but also the
      epilepsy per se. No significant differences in latencies and amplitudes of evoked
      potentials (VEP, BAEP, SEP and especially ERP-300) were measured after LTG.
      Preliminary results obtained in this study supported good efficacy and
      tolerability and especially lack of unfavourable influence of LTG on
      neuropsychological functioning in young previously untreated patients with
      epilepsy.

PMID- 11977354
TI  - Demographic structure of patients taking dental X-rays in the Lublin region.
AB  - Intraoral radiograms are the most often taken X-ray pictures in humans and the
      dose of radiation necessary for such radiogram is very low. However, there exists
      a considerable anxiousness in Polish society towards Roentgen radiation making
      patients avoid dental X-rays even when these are indispensable in dental
      treatment. The aim of the study was the evaluation of demographic structure of
      patients taking intraoral radiograms. The material consisted of 1,014 adults
      undergoing dental treatment, who had intraoral radiograms taken in the Department
      of Dental and Maxillofacial Radiology in 2000. After the informed consent the
      patients filled an anonymous questionnaire of standardised interview. The
      collected records were analyzed statistically and data such as age, sex,
      education, place of residence, employment and income were considered. The
      demographic structure of population of patients who had intraoral radiograms
      taken in the course of dental treatment differs considerably from the structure
      of the general population. These differences were marked especially when taking
      into account the level of education, employment and place of residence of the
      studied patients. Inhabitants of rural communities, people with lower level of
      education as well as older patients avoid taking dental radiograms irrationally
      fearing ionizing radiation. The economic factor is also important and influences
      the structure of patients in the domain of employment and income.

PMID- 11977355
TI  - The case of the submandibular gland sialolith.
AB  - The authors describe a case of a sialolith formation in a submandibular gland
      over 2 years. A large salivary stone is demonstrated radiologically and surgical
      treatment is described.

PMID- 11977357
TI  - Cervicofacial actinomycosis--an issue still present.
AB  - On the basis of the literature the authors present the etiopathogenesis, entry of
      the infection and the course of cervicofacial actinomycosis and they describe
      treatment possibility of patients with actinomycosis. They also concentrate on
      the present, atypical clinical picture of the disease, especially in the initial
      period. They find the sanation of the oral cavity is necessary for a complete
      recovery.

PMID- 11977356
TI  - Iron content in rats' teeth in glucocorticoid-induced osteoporosis.
AB  - On the basis of atomic absorption spectrophotometry rat teeth iron levels in
      glucocorticoid-induced osteoporosis were measured. Hydrocortisone caused
      decreasing of the iron level in rat teeth after both 4 and 8 weeks of the
      duration of the experiment. The other drugs used in osteoporosis treatment
      (calcium and calcitonin) administered together with hydrocortisone or separately
      also influenced the content of this ion in rats' teeth.

PMID- 11977358
TI  - The case of low symptoms carotid cavernous fistula.
AB  - The authors describe the case of a patient with posttraumatic carotid cavernous
      sinus fistula with a complex of low clinical syndromes. Attention was drawn to
      oligosymptomatic fistula causing diagnostic difficulties in maxillofacial surgery
      practice. The study presents diagnostic and treatment methods and their results.

PMID- 11977359
TI  - Ultrasound images of thrombosis of caval vein inferior--three selected cases.
AB  - Thrombosis of vena cava inferior can occur as complication of numerous diseases.
      Because of a variety of causes, the clinical signs accompanying thrombosis are
      often ambiguous, which is the cause of delay in initiation of appropriate
      treatment. This article presents three interesting cases of thrombosis of vena
      cava inferior in children accompanying extensive burn, the Budd-Chiari syndrome,
      and prolonged presence of catheters in vessels. The use of ultrasound in B
      presentation, Color Doppler and Power Doppler has enabled early diagnosis and
      application of appropriate treatment.

PMID- 11977360
TI  - CD45RO and CD45RA cells in peripheral blood in psoriatic patients preceded by an
      infection.
AB  - A group of 28 psoriatic patients was examined before a topical treatment and
      afterwards. Samples of peripheral blood were obtained and analysed in a flow
      cytometry with respect to subpopulation of lymphocytes with a particular care
      paid to percentage and expression of CD45RO and CD45RA cells. The received
      results were compared with those from the group of 22 healthy controls. The study
      showed that the mean percentage of CD45RO+ cells in the psoriatic patients was
      significantly higher than in the control group (p < 0.005). In the psoriatic
      group there were no statistically significant differences between the values of
      any of the parameters studied before and after the treatment.

PMID- 11977361
TI  - Selected issues in the field of aesthetic dentistry.
AB  - On the basis of clinical experience and literature the role of colour in
      aesthetic dentistry has been described. Recently the dynamic development of
      aesthetic dentistry can be observed and every opportunity for a dentist to
      include the issues of aesthetics in dental treatment is extremely important. One
      of the most important factors in conservative dentistry as well as in dental
      prosthetics will be proper colour selection for reconstructive restoration,
      filling, inlay and prosthetic restoration.

PMID- 11977362
TI  - Aggression and arrogance phenomenon among school youth as a health risk factor
      for teachers.
AB  - Arrogance and aggressive behaviour occur more and more often in our lives.
      Especially at school there are observed negative attitudes of school youth. The
      aim of the study was to estimate the occurrence of aggressive behaviour among
      school youth towards teachers. Research based on questionnaires was carried out
      among 156 teachers (63.5% women and 36.5% men), aged 23-60 (mean 40 +/- 8.9) with
      time of employment ranking from 1-35 years (mean 14 +/- 9.2), working at
      vocational, technical and secondary schools as well as in the last classes of
      primary schools. Generally, aggressive behaviour more often occurs among school
      youth. It mainly includes verbal aggression, disrespectful attitude towards a
      teacher and refusal to follow his instructions. Other kinds of aggressive
      behaviour were observed rarely. More than half of the investigated persons did
      not feel distress at school, some of them only a little. The majority of subjects
      noticed the growing problem of negative behaviour among school youth during the
      last few years. Especially women defined their job as stressful and associated
      stress level with psychosomatic disorders (most often the increasing nervous
      stress and headache) they suffered from. Therefore, some teachers had to use
      tranquillizers to reduce stress level at work.

PMID- 11977363
TI  - The influence of cisplatinum and goserelinum on the magnesium and calcium level
      in rat serum.
AB  - The influence of cisplatinum and goserelinum on the magnesium and calcium
      concentration in rat serum has been studied. The cisplatinum induces decrease in
      serum magnesium concentration (to 70%), and calcium concentration (to 63%).
      Goserelinum activity was similar to cisplatinum activity. The magnesium
      concentration decreased to 60%, and calcium to 44%. In condition of cisplatinum
      and goserelinum activity the hypomagnesemia and hypocalcemia were noted.

PMID- 11977364
TI  - Bleeding from gastro-intestinal tract caused by benign tumours of the small
      bowel.
AB  - The paper discusses three cases of mass bleeding from the upper section of
      gastrointestinal tract caused by benign tumours od the small bowel. The technique
      of the intraoperative endoscopic examination of gastrointestinal tract has been
      described. The authors stress the usefulness of this technique in the case when
      the source of bleeding is difficult to localise.

PMID- 11977365
TI  - Proliferating nuclear antigen (PCNA) as a prognostic factor of squamous cell
      carcinoma of the oesophagus.
AB  - Proliferating nuclear antigen (PCNA) plays an important role both in the process
      of replication and repair of DNA. The aim of the carried out investigations was
      to find out if there was any correlation between the depth of malignant
      infiltration, invasion of lymph nodes, presence of metastases in extra-regional
      lymph nodes, the length of patients' survival, and the value of PCNA
      proliferating index analysed in biopsy specimens before the operation, taken from
      60 patients with oesophageal squamous cell carcinoma. In the groups with advanced
      squamous cell carcinoma of the oesophagus the following statistic correlation was
      found between PCNA proliferating index and: invasion of lymph nodes--p < 0.04;
      degree of carcinoma progression--p < 0.01; and blood vessels infiltration--p <
      0.001. The survival of patients with carcinomas of high (> 50%) and low (< 50%)
      PCNA index did not differ significantly. It results from the above investigations
      that high values of PCNA index may indicate the presence of metastases in
      lymphatic nodes and the degree of progression of oesophageal carcinoma.

PMID- 11977367
TI  - The evaluation of intensity of traffic noise in different points of town routes.
AB  - The aim of the study was measuring noise intensity in the selected points of
      traffic routes in the town of Lublin. Investigations were carried out at 11
      points located in the centre of the town and at escape roads. Noise value levels
      showed variable intensity, the highest being observed in the morning and
      afternoon hours. The highest mean level of noise intensity was recorded at the
      crossing of Solidarnosci Avenue and Sikorskiego Street, and the lowest in
      Narutowicza Street.

PMID- 11977366
TI  - p35 protein as a prognostic factor of squamous cell carcinoma of the oesophagus.
AB  - Communications show that in squamous cell carcinoma of the oesophagus one can
      often observe overexpression of p53 protein. Wild type p53 protein suppresses
      cells' growth, and mutated p53 acts as onkogene. Gene p53 mutations usually lead
      to stabilization and accumulation of p53 protein, and, as a result they become
      detectable by immunochemical methods. Overexpression of p53 has been observed in
      28 (46.7%) out of 60 collected specimens. It has no connection with sex, age,
      histological differentiation, category (pT) of tumour, infiltration (pN) of lymph
      nodes and extent of metastases (pMlym+). p53 protein expression has no
      correlation with survival predictability.

PMID- 11977368
TI  - Ultrastructural changes in the receptor parts of retinal rods in experimental
      alloxan-induced diabetes in rabbits.
AB  - Mature rabbits were administered a single dose of alloxan at the dose 100 mg/kg
      b.m. After 3 and 6 weeks and after 3 and 6 months, the samples of the retina were
      taken from the areas immediate to the papilla of the optic nerve. Ultrathin
      sections were dyed according to the Reynold's method, and the receptive parts of
      the rods were examined under electron microscope BS-500 Tesla. After 6 weeks
      following alloxan administration, distinct morphological changes in the form of
      enlargement of certain discs in the receptive parts of rod cells were observed.
      After 3 months the majority of the discs was damaged, and after 6 months only
      single, quite well preserved rod cells were found to be present in the retina.

PMID- 11977369
TI  - Histological changes in the retina in experimental alloxan-induced diabetes in
      rabbits.
AB  - Mature rabbits were given a single dose of alloxan at the dose of 100 mg/kg of
      b.m. After 3 and 6 weeks and after 3 and 6 months the retina samples were taken
      from the areas immediate to the papilla of the optic nerve. Half-thin sections
      were stained with Swiss blue and azure, and the changes in the particular layers
      were evaluated under the light microscope. Morphological changes in the form of
      decreased number of neurones (especially ganglionic) and narrowed layer of rods
      and cones occurred after 6 weeks. After 3 months even further increase in the
      number of neurones and atrophy of the pigmented epithelium cells were observed.
      After 6 weeks nearly total atrophy of ganglionic neurones and distinct narrowing
      of all the layers were found.

PMID- 11977370
TI  - Histological examination of the thyroid after experimental administration of
      Metizol.
AB  - The investigations were carried out on thyroids of white Wistar rats which were
      given Metizol for 3 days, 3 and 6 weeks at the dose of 1 mg/kg of b.m. for 24
      hrs. The samples were stained with hematoxylin and eosin and by the PAS method.
      The following changes were observed: 1. Three-day administration of Metizol
      resulted in the decrease in the quantity of colloid; the secretory epithelium
      became uniform--i.e. cubic; the quantity of the interfollicular tissue increased.
      2. Three-week administration of Metizol resulted in appearing of colloid stained
      differently than in the control group; secretory epithelium cells were of
      different height (cubic and cylindrical), a considerate congestion of the gland
      was visible, the quantity of the interfollicular tissue increased. 3. After 6
      weeks of Metizol administration the morphological picture of the thyroid became
      similar to that of the control group.

PMID- 11977371
TI  - Embryofetotoxicity of acetaminophen (paracetamol) in experimental in vivo model.
AB  - The aim of the study was to evaluate the toxic effect of acetaminophen on rat
      fetuses. Acetaminophen, suspended in Tween 80 solution, was administered once a
      day, orally by a stomach tube to pregnant Wistar rats from day 8th to 14th of
      pregnancy at the dose: 3.5 (P1), 35.0 (P2), 350.0 mg/kg (P3). The pregnant
      females were terminated on day 21st of pregnancy and the number of corpora lutea,
      implants, resorptions, and fetuses was counted. The fetuses and the placentas
      were weighed and the length of the fetuses and their tails were checked. The
      slides of the fetal liver were examined via light microscopy in four stains:
      hematoxylin and eosin, silver Gomorii, van Giesson, and periodic acid-Schiff.
      There was a statistical (p < 0.05) difference in fetal body length in group P3
      without any macroscopic malformation, except for the non-statistical number of
      subcutaneous ecchymoses. Histological adaptive changes of the fetal liver were
      observed occasionally in all the studied groups. In conclusion, the oral
      administration of acetaminophen caused an embryotoxic effect in the highest doses
      without any macroscopic malformation, and only slightly impaired morphology of
      the rat fetal liver.

PMID- 11977373
TI  - Hearing loss in chronic alcoholics.
AB  - Alcohol has a local and general influence. A specially harmful effect is observed
      when it is abused--used frequently and in high concentrations. Chronic excessive
      drinking of alcohol results in sight deterioration, hearing loss and psychical
      disorders. The study aimed at evaluating the degree and place of the hearing
      organ damage in 30 alcoholics. They were subjected to audiologic examinations
      including: pure-tone and impedance audiometry, otoacoustic emissions and evoked
      brain stem responses tests. The patients were diagnosed with sensorineural
      hearing loss, lack of otoemission indicating the damage of outer hear cells as
      well as hearing pathway damage in the brain stem.

PMID- 11977372
TI  - The application of synthetic hydroxyapatite in children and adolescents in
      various clinical cases.
AB  - The possibility of application of HA-BIOCER synthetic hydroxyapatite in the
      treatment of enamel hypoplasia in children and adolescents manifested by
      mineralisation disorders, enamel underdevelopment, enamel deficiency and
      oversensitivity to mechanical, thermal and chemical stimuli was evaluated. The
      possibility of applying the same preparation in case of enamel fractures and
      teeth injuries type I according to Ellis was also examined. It was found that the
      application of hydroxyapatite stimulates processes of remineralization in
      decalcified places. It also causes removal of tooth oversensitivity to thermal
      and mechanical stimuli by closing open dentinal tubules or decrease in their
      size. HA-BIOCER preparation brings about smoothing and lighting of hypoplastic
      foci, improves aesthetic appearance and is not toxic to patients.

PMID- 11977374
TI  - Parental accounts of blaming within the family: a dialectical model for
      understanding blame in systemic therapy.
AB  - The aim of this study was to further understanding of blame in systemic therapy.
      Five families were chosen by their therapeutic team as engaging in blaming of a
      kind that the therapists found difficult to work with. Couples from each of the
      five families participated. A video extract from therapy identified by therapists
      as typifying blaming within the family was used as a focus for semistructured
      interviews with each parent. Transcripts were analyzed according to the
      procedures of grounded theory. On the basis of this inductive qualitative
      analysis, a framework of understanding emerged from the data consisting of the
      core category, "dialectical understanding," and an accompanying set of
      overarching themes. These themes capture the way in which participants oscillated
      among 13 dialectics in their discussion of blame within their family and within
      family therapy. The model provides a framework for analyzing the style and
      content of therapy conversations with a view to helping therapists facilitate
      therapeutic change in this difficult client group.

PMID- 11977375
TI  - Antecedents and consequences of negative marital stressors.
AB  - Many couples seeking therapy report the occurrence of severe, negative marital
      stressors (e.g., infidelity, threats of marital dissolution). In addition,
      existing research has demonstrated that these marital stressors precipitate Major
      Depressive Episodes and psychological symptoms. This longitudinal study examines
      the antecedents and consequences of negative marital stressors to help clinicians
      and researchers develop interventions that might prevent these stressors and
      their outcomes. Forty-one women completed a semistructured interview and measures
      of marital discord and depressive symptoms within one month after experiencing a
      marital stressor (baseline) and at a 16-month follow up. The results indicate
      that baseline marital discorded contributes to the occurrence of additional
      marital stressors during the follow-up period. Although baseline depressive
      symptoms do not predict additional marital stressors, depressive symptoms along
      with marital discord predict future depressive symptoms. Finally, baseline
      marital discord and additional marital stressors contribute to future marital
      dissolution. Clinical and research implications are discussed.

PMID- 11977376
TI  - Developing culturally competent marriage and family therapists: treatment
      guidelines for non-African-American therapists working with African-American
      families.
AB  - To serve African-American families effectively, marriage and family therapists
      need to develop a level of cultural competence. This content analysis of the
      relevant treatment literature was conducted to examine the most common expert
      recommendations for family therapy with African Americans. Fifteen specific
      guidelines were generated, including orient the family to therapy, do not assume
      familiarity, address issue of racism, intervene multi-systemically, do home
      visits, use problem-solving focus, involve religious leader, incorporate the
      father, and acknowledge strengths. Conceptual and empirical support for each
      guideline is discussed, and conclusions are made regarding culturally competent
      therapy with African-American families.

PMID- 11977377
TI  - The Cultural Genogram: experiences from within a marriage and family therapy
      training program.
AB  - The purpose of this article is to illustrate and demonstrate the use of the
      Cultural Genogram (CG) in a graduate-level course in gender and culture for
      family therapists-in-training at a large Midwestern university's accredited
      program in family therapy. Although the importance of the CG as a training tool
      is delineated by Hardy and Laszloffy, very little information exists about the
      actual implementation and usefulness of this tool within a training program for
      family therapists. In this article, we present a qualitative research study of
      the lived experiences of a class of women from diverse cultures as they
      constructed and presented their CGs. We discuss the basic curriculum and
      structure of the course in which the CG was used, the process the class members
      developed to create and present their CGs, the effects of presenting the CGs, and
      a set of recommendations and ideas for further exploration.

PMID- 11977378
TI  - Transforming an MFT program: a model for enhancing diversity.
AB  - Marriage and family therapy programs need to go beyond the typical practices of
      recruiting and retaining students of color. Marriage and family therapy educators
      must assume positions of leadership by transforming graduate programs to reflect
      a deep, active, systemic commitment to both diversity and social justice. In this
      article, we argue that it is through this type of transformation that programs
      become truly ready to support students of color and to prepare all therapists to
      advocate for equity in a diverse, often unfair society. This article offers a
      model that addresses readiness, recruitment, retention, assessment, and
      professional development from this perspective.

PMID- 11977379
TI  - Training family therapists to assess for and intervene in partner abuse: a
      curriculum for graduate courses, professional workshops, and self-study.
AB  - Partner abuse is an epidemic with potentially dire consequences for individuals,
      families, and society. Family therapists must be able to competently assess for
      and intervene in abuse situations. This article presents a curriculum designed to
      provide family therapists with introductory knowledge and skills for the
      assessment and intervention of partner abuse. The curriculum, which is informed
      primarily by feminist and multicultural theories and practices, can be used in
      graduate courses, professional workshops, and for self-study.

PMID- 11977380
TI  - Family therapists' ethical decision-making processes in two duty-to-warn
      situations.
AB  - This quantitative study investigated the ethical decision-making process of 177
      Missouri members of the American Association for Marriage and Family Therapy
      using two in-session duty-to-warn scenarios of child abuse and HIV transmission.
      The components of the critical-evaluative level of ethical decision making
      include the lower-level decision components of personal/therapeutic response,
      professional ethics, and legal considerations/laws of the State, and the
      components of the higher-level decision base, the meta-ethical principles, which
      are nonmaleficence, autonomy, beneficence, fidelity, and justice. Statistical
      results indicated that in the child abuse scenario, professional ethics and legal
      considerations/laws of the State were considered most important, whereas in the
      HIV scenario, professional ethics were the preferred lower-level decision base.
      Across scenarios, the preferred higher-level decision base was nonmaleficence.
      There were differences across the child abuse and HIV scenarios in the perceived
      significance of the remaining lower-level decision base items as well as
      differences in perceived significance and ordering of the remaining meta-ethical
      principles. Limitations are discussed.

PMID- 11977381
TI  - Considering justice: an exploratory study of family therapy with adolescents.
AB  - Feminist approaches to therapy with adolescents emphasize an empowering focus on
      the strengths of adolescents while simultaneously insisting that therapists
      become aware of their own biases toward today's adolescents. However, a review of
      the family therapy literature finds little mention of feminist approaches for
      addressing injustices (e.g., family scapegoating, negative societal views of
      adolescents, and gender oppression) that arise in family therapy with
      adolescents. Therefore, this study explores clinical approaches and resources
      suggested by a surveyed group of self-identified feminist family therapists. In
      addition, we also recommend several approaches and resources that will aid family
      therapists in creating a more just climate for family therapy with youth.

PMID- 11977382
TI  - Characteristics of effective providers of marital and family therapy in rural
      mental health settings.
AB  - Characteristics of effective providers of marital and family therapy (MFT) in
      rural mental health settings were investigated. The survey sample included 74
      members of the National Association for Rural Mental Health who, through a
      modified Delphi process, created a composite picture of effective MFT providers.
      The findings yielded six major rank-ordered characteristics of effective MFT
      providers in rural mental health settings, with effective skills in MFT ranked
      first. Rural community understanding, appreciation and participation ranked
      second. Specific competencies contributing to each major characteristic were also
      identified and are discussed. Recommendations for use of this information are
      provided.

PMID- 11977383
TI  - A review of three comprehensive premarital assessment questionnaires.
AB  - Three comprehensive premarital assessment questionnaires (PAQs) are described,
      evaluated on their psychometric characteristics, and compared. They include the
      PREmarital Preparation and Relationship Enhancement (PREPARE) questionnaire, the
      Facilitating Open Couple Communication, Understanding and Study (FOCCUS)
      questionnaire, and the RELATionship Evaluation (RELATE). Recommendations for
      using each PAQ are discussed.

PMID- 11977384
TI  - The Boundary Violations Scale: an empirical measure of intergenerational boundary
      violations in families.
AB  - This article reviews the development of a new measure to assess children's
      perceptions of intergenerational boundary violations in families. The Boundary
      Violations Scale is a theoretically derived instrument consisting of 12 items.
      Principal components analysis using data from 119 young adolescents from diverse
      ethnic backgrounds (i.e., 56% Hispanic and 44% non-Hispanic) revealed three
      factors (promoting maturity, forming coalitions, and communicating as peers) that
      are consistent with the behavioral manifestations of this construct as posited by
      structural family theory. The validity of the measure was supported by
      significant correlations with theoretically relevant measures of family processes
      and child adjustment as reported by children and their mothers.

PMID- 11977385
TI  - [Functional and molecular aspects of anti-inflammatory effects of low-dose
      radiotherapy].
AB  - PURPOSE: Low-dose radiotherapy (LD-RT) with single fractions between 0.1 and 1.0
      Gy is known to exert an antiinflammatory effect. Although different mechanisms
      for the clinical efficiency were proposed, only few experimental data are still
      available. This paper focuses on functional and molecular aspects of LD-RT.
      METHODS AND RESULTS: The antiinflammatory efficiency of LD-RT in clinical studies
      could be confirmed in experimental models of osteoarthritis and rheumatoid
      arthritis. In a model of adjuvants arthritis, 5 x 1.0 Gy as well as 5 x 0.5 Gy,
      given at the maximum of the acute inflammation, could prevent clinically and
      histologically progression of the disease without affecting existing signs of
      inflammation. The effect of LD-RT on the adhesion of peripheral blood mononuclear
      cells (PBMC) and endothelial cells (EC) was analyzed in in-vitro assays. In the
      dose range between 0.3 and 0.7 Gy almost 4 hours after irradiation adherent cells
      reached a relative minimum of adhesion compared to unirradiated controls. In PBMC
      an discontinuous increase of apoptosis with a maximum between 0.3 and 0.5 Gy, the
      proteolytic shedding of L-selectin and an increased expression of the
      antiinflammatory cytokine interleukin 10 as well as downregulation of TNF alpha
      could be identified as potential mechanisms for the observed reduced adhesion.
      Conversely, reduced expression of E-selectin and an increased induction of
      transforming growth factor beta (TGF beta 1) with a maximum at 0.5 Gy could be
      observed in endothelial cells. Macrophages immigrating the site of inflammation
      are known to express inducible nitrix-oxide synthase (iNOS), which in turn
      mediates cytotoxic and immunmodulatory effects by producing nitric oxide (NO). LD
      RT of stimulated macrophages within the dose range between 0.6 and 1.25 Gy
      reduced NO production and iNOS-protein expression without affecting iNOS-mRNA
      expression. CONCLUSION: Our experimental data have confirmed the antiinflammatory
      efficiency of LD-RT in vitro and in vivo, indicating effects on different
      cellular components and mechanisms of inflammation. The regulation of the
      adhesion between PBMC and endothelial cells and the effects on activated
      macrophages may mediate the antiinflammatory properties of LD-RT. Ongoing
      experiments will help to clarify the molecular mechanism.

PMID- 11977386
TI  - Conformal proton radiation therapy for pediatric low-grade astrocytomas.
AB  - BACKGROUND: To evaluate the safety and efficacy of proton radiation therapy (PRT)
      for intracranial low-grade astrocytomas, the authors analyzed the first 27
      pediatric patients treated at Loma Linda University Medical Center (LLUMC).
      PATIENTS AND METHOD: Between September 1991 and August 1997, 27 patients (13
      female, 14 male) underwent fractionated proton radiation therapy for progressive
      or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18
      years (mean: 8.7 years). Tumors were located centrally (diencephalic) in 15
      patients, in the cerebral and cerebellar hemispheres in seven patients, and in
      the brainstem in five patients. 25/27 patients (92%) were treated for
      progressive, unresectable, or residual disease following subtotal resection.
      Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic
      pathway tumors were treated without histologic confirmation. Target doses between
      50.4 and 63.0 CGE (Cobalt Gray Equivalent, mean: 55.2 CGE) were prescribed at 1.8
      CGE per fraction, five treatments per week. RESULTS: At a mean follow-up period
      of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all
      located within the irradiated field), and 4/27 patients had died. By anatomic
      site these data translated into rates of local control and survival of 87% (13/15
      patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86%
      (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5
      patients) for tumors located in the brainstem. Proton radiation therapy was
      generally well tolerated. All children with local control maintained their
      performance status. One child with associated neurofibromatosis, Type 1,
      developed Moyamoya disease. All six patients with optic pathway tumors and useful
      vision maintained or improved their visual status. CONCLUSIONS: This report on
      pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and
      efficacious 3-D conformal treatment modality. Results are encouraging for central
      tumors as well as large optic pathway tumors, where dose conformity is of
      particular importance; yet it is difficult to achieve. Longer follow-up time is
      needed to fully evaluate the benefits of normal tissue sparing.

PMID- 11977387
TI  - Radiotherapy of internal mammary lymph nodes in breast cancer. Principle
      considerations on the basis of dosimetric data.
AB  - BACKGROUND: Radiotherapy of internal mammary lymph nodes (IMN) in breast cancer
      is discussed controversially due to its potential toxicity and debatable
      efficacy. Aim of the present study was to assess the cardiac and lung dose in 3-D
      planned radiotherapy and to discuss these results with regard to arguments pro
      and contra IMN irradiation. PATIENTS AND METHODS: 32 patients underwent 3-D
      planning (Helax TMS) for irradiation of breast and IMN in three different
      techniques either using separate IMN fields (A, B) or a wide tangent (C). For
      each technique the respective doses to the heart (including the base of the aorta
      and the ostium of the coronary arteries) and lung were analyzed in dose volume
      histograms. RESULTS: The mean dose to the heart (left side irradiation) was 6.4
      Gy (A), 8.1 Gy (B) and 3.8 Gy (C). The mean dose to the lung was 11.7 Gy (A),
      15.4 Gy (B) and 10.2 Gy (C). The 10-Gy isodose comprised 19.5% (A), 32.9% (B) and
      5.6% (C) of the heart (left breast). The respective values for the 20-Gy isodose
      were 7.8, 11.5 and 4.4%. The irradiated volumes of the lung were 37.7% (A), 52.7%
      (B) and 20% (C) in the 10-Gy isodose. The 20-Gy isodose comprised 16.7% (A),
      28.3% (B) and 17.8% (C). CONCLUSION: Whether radiotherapy of the IMN may improve
      treatment results in breast cancer is currently unresolved. However, the present
      data indicate that relevant cardiovascular side effects are unlikely to occur.
      Thus, the indication should be considered on the basis of individual risk
      factors.

PMID- 11977388
TI  - Postoperative radiotherapy in the treatment of Ewing tumors: influence of the
      interval between surgery and radiotherapy.
AB  - BACKGROUND: The impact of the timing of postoperative irradiation was evaluated
      in patients with Ewing tumors who received postoperative irradiation. PATIENTS
      AND METHODS: 153 patients treated in the CESS 86 and EICESS 92 trials were
      evaluated in a retrospective analysis. They received surgery and postoperative
      irradiation as local treatment modalities. In 46 patients, postoperative
      irradiation was started within 60 days after surgery, in 107 patients after more
      than 60 days. A median dose of 45 Gy was administered. The median follow-up was
      70 months. RESULTS: There was no substantial difference between the two groups
      concerning risk factors for local failure and survival. The local control rate
      after 5 years was 98% in the group with early onset of radiation and 92% in the
      group with later onset (n.s.). There is no difference in event free survival
      between the two groups (both 64% after 5 years). If the cutpoint of the onset of
      postoperative irradiation was chosen after 90 days, there was no difference in
      local control or event free survival. CONCLUSIONS: Patients with early onset of
      postoperative irradiation show a trend for improved local control compared to
      patients with a later onset; the difference is statistically not significant.
      This trend has no influence on survival.

PMID- 11977389
TI  - DNA ploidy of primary and recurrent irradiated laryngeal tumors.
AB  - PURPOSE: Radiosensitivity of diploid laryngeal cancers, as compared with that of
      aneuploid ones, appears to be increased. However, no conclusive data exist. If a
      causal relationship exists, then recurrent laryngeal cancer after irradiation
      should predominantly be characterized by aneuploidy. PATIENTS AND METHODS: To
      test this hypothesis we compared ploidy of 24 primarily irradiated laryngeal
      cancers and their subsequent recurrences. T and N stages were assessed in
      accordance with the TNM classification system of the UICC. With flow cytometry
      DNA ploidy was assessed. RESULTS: 1. Ploidy of 16 locally recurrent tumors did
      not differ from those of primary tumors, i.e. ten and six recurrences of diploid
      and aneuploid primary tumors, respectively, remained unchanged, 2. recurrences of
      four aneuploid primary tumors showed diploidy, 3. recurrences of four diploid
      primary tumors showed aneuploidy. CONCLUSIONS: The results of our study do not
      support the hypothesis that recurrent laryngeal cancer after irradiation of the
      primary tumor is characterized by aneuploidy.

PMID- 11977390
TI  - Chromosomal aberration in peripheral lymphocytes and doses to the active bone
      marrow in radiotherapy of prostate cancer.
AB  - BACKGROUND AND PURPOSE: Radiotherapy plays an important role in the management of
      prostate cancer. Epidemiological data indicate a small but significant risk of
      radiation-induced leukemia after radiotherapy which might be related to the high
      mean bone marrow dose associated with radiotherapy of prostate cancer. The
      purpose of the study was to investigate the relation between the mean bone marrow
      dose and unstable chromosome aberrations in peripheral blood lymphocytes in
      patients undergoing conformal radiotherapy for prostate cancer as a possible
      indicator of risk. Endometrial cancer patients were also included for comparison.
      PATIENTS AND METHODS: Nine patients, six with prostate cancer (60-73 years old)
      and three with endometrial cancer (61-81 years old) treated with radiotherapy
      were included in the study. The non-bony spaces inside the pelvic bones were
      outlined on every CT slice using the treatment planning system and mean doses to
      the bone marrow calculated. Blood samples of the patients were obtained at
      different times before, during and at the end of treatment. Lymphocytes were
      cultured in the usual way and metaphases scored for dicentric aberrations.
      RESULTS: 46 samples from nine patients were obtained. The mean number of
      metaphases analyzed per sample was 180 with a range from 52 to 435. The mean bone
      marrow doses for prostate cancer patients ranged from 2.8 to 4.2 Gy and for
      endometrial cancer patients from 12.8 to 14.8 Gy. The aberration yield increased
      with the planning target volume and the mean bone marrow dose. CONCLUSION: The
      yield of dicentric aberrations for prostate cancer patients correlated closely
      with the mean bone marrow dose albeit the induction of dicentrics occurred in
      mature T lymphocytes most of which were probably in transit through the
      irradiated volumes. Therefore, the observed relationship between dicentrics and
      mean bone marrow doses are indirect.

PMID- 11977391
TI  - [Lung dose depending on exact patient positioning during total body irradiation
      (TBI). Isoeffectiveness considerations to assess the risk of interstitial
      pneumonia after TBI].
AB  - PURPOSE: In this case report, we studied the effect of patient's movements on
      total lung dose during total body irradiation (TBI). The dose-effect relationship
      regarding the development of interstitial pneumonitis and the problem of defining
      a threshold value are discussed. Based on considerations about the isoeffects we
      calculated the pneumonitis risk in dependence of increasing lung dose. PATIENTS
      AND METHOD: We calculated dose-volume histograms of the lung for defined lateral
      deviations (0-3 cm) from the isocenter. Total dose was 12 Gy, given in six
      fractions over 3 days. Lung shields were used after a total dose of 9 Gy. Lung
      shields were transferred into the Helax-TMS planning system to quantify the
      influence of lateral deviation to lung dose. RESULTS: The child's lateral
      deviation amounted up to 3 cm. Median dose of the whole lung amounted up to 11.64
      Gy depending on lateral deviation. DISCUSSION: In TBI, the lung limits the total
      dose. To estimate the risk of radiation pneumonitis, we calculated the
      isoeffective lung dose of our TBI regime for a fractionation scheme of 2 Gy daily
      using a formalism of van Dyk. The increase of median lung dose from 9.76 to 11.64
      Gy would isoeffectively correspond to the increase from 19 Gy (no deviation) to
      20.9 Gy (3 cm lateral deviation) with conventional fractionation. According to
      Burman, a pneumonitis risk of approximately 20% could be expected. CONCLUSION:
      With an estimated pneumonitis risk of approximately 20%, in indication for
      irradiation in general anesthesia seems to be reasonable. This is practicable in
      cooperation with radiation oncologists, anesthesists and pediatricians and should
      be included into therapeutic concepts.

PMID- 11977392
TI  - [Intellectual outcome in children after total brain irradiation and
      chemotherapy].

PMID- 11977393
TI  - [Intracoronary gamma brachytherapy significantly lowers the restenosis rate after
      PTCA and stent implantation].

PMID- 11977394
TI  - [Novel data on mammography: invitation to organized mammographic screening
      substantially reduces breast carcinoma mortality].

PMID- 11977395
TI  - [Prognostic factors in lymph node negative breast cancer].

PMID- 11977396
TI  - [Comparison of epirubicin and cyclophosphamide in 2-dose levels and classical CMF
      protocol in node-positive breast cancer. An adjuvant Phase III trial].

PMID- 11977397
TI  - [Accepting personal body appearance].

PMID- 11977398
TI  - [Sex differences in body image of adolescents and significance for self esteem].
AB  - Previous findings show that the body image of adolescents is in the first place
      gender related. However, most studies primarily focus on body cathexis. The
      present study, which was conducted in the context of a multi-dimensional
      perspective, refers to the question of gender differences in the adolescent's
      body image. Furthermore, it examines what relevance the single components of the
      body image have for general self-esteem. Therefore, we tested 326 adolescents
      aged 13 to 16 using questionnaires. The results indicate that there is primarily
      evidence for gender differences, whereas age related differences can hardly be
      found: Female adolescents differ from their male counterparts for example in the
      following aspects: they have a higher body awareness, a higher dissatisfaction
      with their shape, a lower perceived athletic competence and stronger feelings of
      depersonalisation. However, considering the effect sizes, it becomes clear that
      the differences mainly come up to only a low extend. Besides, the individual body
      image profile is hardly suitable to determine the gender of the adolescents.
      Furthermore, using regression analysis it was shown that altogether the body
      image has the same relevance for males and females in order to predict self
      esteem. Nevertheless, there are special body image components that help to
      predict body image for boys and girls differently. The results show that the body
      image of adolescents is gender-depending but not gender specific. So demand
      arises for investigating the determinants of the development of the adolescent's
      body image that go beyond the gender-variable.

PMID- 11977399
TI  - [Aspect of body image in physically disabled youth].
AB  - The following study compares body awareness and body satisfaction of physically
      handicapped and normal adolescents. In addition the correlations between self
      image were investigated in the group of handicapped adolescents. The comparison
      showed handicapped youths to have more negative body image. The handycap
      associated differences between the 2 groups were paralleled by equally
      significant gender-associated differences within the group of handicapped
      adolescents. The differences are similiar to ones described in the literature as
      typical for normal adolescents. No evidence was found of minimizing or disavowing
      the illness or of shame for the handicapped body. Instead, a strong wish for
      contact with healthy youths was evident. The results of the study underline the
      importance of body-associated psychotherapeutic intervention supplementing the
      many therapeutic measures of handicapped adolescence.

PMID- 11977400
TI  - [Influence of social support by parents and peers on physical complaints in
      students].
AB  - The mechanisms mediating the connection between school-specific stressors and
      physical complaints, indicating psychosocial strain, are still unclear. Assuming
      that social support is an important part of the coping process, it is
      hypothesized that different sources of social support may have varying effects on
      the degree of physical complaints. The sample consisted of 326 students--182
      girls and 144 boys--in grades 6 and 8. On average, female adolescents reported
      physical symptoms to a greater extent than did male adolescents. Confronted with
      school-specific stressors, girls showed a higher willingness to make use of peer
      support. For boys and girls a high degree of anticipated peer-support was linked
      to a higher extent of physical complaints. Parental support buffered the effect
      of bad grades regarding the extend of physical complaints only for girls. The
      assumption of a longitudinal link between social support, school achievement, and
      the degree of physical complaints one year later was not supported. Results
      emphasize the importance of further research regarding the functions of different
      sources of social support for boys and girls.

PMID- 11977401
TI  - [Role of family in development of neurophysiological manifestations in children
      with migraine].
AB  - Migraine is a familial disorder. The aim of this study was to compare the
      relationship between specific neurophysiologic pathogenetic mechanisms of
      migraine such as abnormal information processing and enhanced cortical
      excitability on the one hand, and parent-child-interactions and personality
      traits such as neuroticism and extraversion on the other hand in migraine and
      healthy families. The correlation and factor analyses demonstrated that the
      stronger the control over a child and the more intensive the suppression of a
      child's independence by a parent during a stressful situation in migraine
      families, the more pronounced the loss of habituation of the contingent negative
      variation (CNV), and the greater the neuroticism in a migraine child. The CNV
      amplitude was independent of psychosocial conditions in the family but
      represented similarities in information processing between parents and their
      children suffering from migraine. This could be possibly explained by genetic
      influences on information processing in migraine. In healthy families only the
      relationship between parameters of parent-child-interaction could be observed.
      This investigation demonstrates that the neurophysiological disposition to a
      migraine attack as well as personality traits in migraine could be influenced by
      psychosocial factors such as parent-child interactions and that different
      parameters of information processing in headache patients are related to either
      non-genetic familial conditions (habituation) or functional genetic factors
      (amplitude).

PMID- 11977402
TI  - [Familial body concepts and illness attributions in primary headache in childhood
      and adolescence].
AB  - Empirical evidence of the important role of the family in primary pediatric
      headache has grown significantly in the last few years. The connections between
      the process of dysfunction and family interaction are, however, still partly
      unclear. From a constructivistic point of view, a suitable approach is to focus
      on social-cognitive factors. In this study, we tested on the basis of exploratory
      results gained from family questionnaires (n = 39 families with a child or an
      adolescent suffering from tension-type headache and/or migraine) whether family
      body concepts and family headache attributions are relevant in this connection.
      In relation to a comparison sample, index patients and their mothers and fathers
      evaluated their own body less positively and displayed a lower level of inner
      body consciousness. In addition, index patients and their fathers and mothers
      tend to have similar attribution preferences with regard to headache. These
      results are illustrated with the aid of case reports and are discussed as an
      indication that the exploration of family body concepts and attribution
      preferences may be clinically useful in the treatment of pediatric headache.

PMID- 11977403
TI  - The media fill (simulation) test is the best method to evaluate aseptic
      processing.

PMID- 11977404
TI  - Choice of culture medium/conditions.

PMID- 11977405
TI  - An industry commentary on regulatory issues--microbiology.

PMID- 11977406
TI  - The development of an injection-molding process for a polyanhydride implant
      containing gentamicin sulfate.
AB  - A production-scale manufacturing process has been developed for
      polyanhydride/gentamicin sulfate implants for the treatment of osteomyelitis.
      Gentamicin sulfate was first dried to an acceptable moisture level by using a
      tumble vacuum dryer. Dried gentamicin sulfate powder and polyanhydride granules
      were separately fed into the twin-screw extruder at a pre-determined metering
      rate using a gravimetric feeding device. The extruded molten mixture was
      solidified to form strands which were subsequently cut into pellets by using a
      pelletizer. The pellets were characterized with respect to copolymer molecular
      weight and drug content uniformity. The pellets were later fed into production
      scale injection-molding equipment for implant fabrication. The injection-molding
      cycle was developed and evaluated in terms of cycle reproducibility. Implants
      were tested and shown to yield an oriented skin-core structure exhibiting a
      desirable in-vitro drug release profile.

PMID- 11977407
TI  - Interferon alpha-2a interactions on glass vial surfaces measured by atomic force
      microscopy.
AB  - Atomic force microscopy was used to study adsorption and adhesion peculiarities
      of interferon alpha-2a on glass and mica surfaces. The specific protein
      adsorption behavior as a function of the pH value was illustrated on mica by
      single molecule imaging, while adhesion forces between interferon molecules and
      inner surfaces of borosilicate glass vials were measured directly under aqueous
      buffer conditions by force microscopy. We found that the adhesion force on Schott
      FIOLAX Type I plus was reduced by 40% of the total adhesion force measured on
      Schott FIOLAX, a standard type I borosilicate glass quality. These results
      reflect the anticipated superiority of the special "Type I plus" coating over
      undesired protein adsorption to glass. In addition, this study gives insight into
      a new method to predict unintended protein adsorption to glass container walls
      and to characterize the adsorption process by force measurement.

PMID- 11977408
TI  - Identification of fungi based on the nucleotide sequence homology of their
      internal transcribed spacer 1 (ITS1) region.
AB  - In this study, we examined the identification of fungi based on the sequence
      homology of the internal transcribed spacer 1 (ITS1) region. A newly designed
      primer pair could amplify the target region of all 42 strains tested. The PCR
      products were sequenced and the sequence homologies were searched by BLAST. It
      was demonstrated that this method is a reliable identification method at the
      genus or species level. At present, available databases are still insufficient to
      identify some fungi, but with the accumulation of further data in the ITS1
      database, this method will be available for the identification of fungi.

PMID- 11977409
TI  - Changes in the cell size of Brevundimonas diminuta using different growth
      agitation rates.
AB  - Brevundimonas diminuta (ATCC 19146) is a standard organism for validation of
      sterilizing-grade membrane filters. Cell size is critical for the determination
      of retention characteristics of 0.2 micron rated membrane filters. In this study,
      cell size changes of B. diminuta cultured under different physiologic states and
      variable agitations at 50, 100 and 200 rpm were measured by a particle size
      analyzer and scanning electron microscope (SEM). The smallest cells were obtained
      at initial stationary phase in saline lactose broth (SLB) as a shaking culture at
      50 rpm. Cells grown under agitation at 50, 100 and 200 rpm showed an increase of
      specific growth rate (mu), about 2.9, 3.6 and 3.6 fold, respectively, compared to
      the non-agitated cells in SLB media. These results suggested that the cell size
      decreased proportionally with increase of the specific growth rate (mu) in SLB.
      These size changes were associated with penetration through a 0.2 micron rated
      cellulose acetate filter. A scale-down filtration system was developed and
      performed bacterial challenge test and bubble point test with cells cultured in
      SLB. Cells grown under agitation conditions in SLB were not retained by 0.2
      micron rated membrane filter.

PMID- 11977410
TI  - Respiratory findings in livestock farmworkers.

PMID- 11977411
TI  - Aerobic exercise, median nerve conduction, and the reporting of study results.

PMID- 11977412
TI  - Effects of an aerobic exercise program on median nerve conduction and symptoms
      associated with carpal tunnel syndrome.

PMID- 11977413
TI  - Evidence that non-ionizing radiation alters men's hormone levels.

PMID- 11977414
TI  - Occupational thyroid cancer?

PMID- 11977415
TI  - Radiographic abnormalities in silica-exposed workers.

PMID- 11977416
TI  - The management of hydrofluoric acid burns.

PMID- 11977417
TI  - Biological versus ambient exposure monitoring of creosote facility workers.
AB  - Traditional methods for monitoring occupational creosote exposure have focused on
      inhalation. However, there is evidence that dermal exposure contributes
      importantly to total systemic dose, as measured by biological monitoring methods.
      This study was conducted to further characterize the relationships between
      inhalation and dermal exposures to creosote, and to compare traditional ambient
      exposure monitoring versus biological monitoring in 36 creosote-exposed wood
      treatment workers. Full-shift personal air samples were obtained, along with post
      shift and next-day urine measurements for 1-hydroxypyrene. There was little or no
      correlation between airborne measures and urinary 1-hydroxypyrene (r2 = 0.05 to
      0.35). More than 90% of 1-hydroxypyrene could be attributed to dermal exposure.
      These data indicate that traditional monitoring methods may be inappropriate for
      creosote workers, raising concerns about the adequacy of methods currently
      mandated by the Occupational Safety and Health Administration.

PMID- 11977418
TI  - The business case for quality mental health services: why employers should care
      about the mental health and well-being of their employees.
AB  - Employers are very concerned about rising mental health care costs. They want to
      know whether their health care spending is improving the health of workers, and
      whether there is a productivity payback from providing good mental health care.
      This article addresses the subject of employee depression and its impact on
      business. The literature suggests that depressed individuals exert a significant
      cost burden for employers. Evidence is mounting that worker depression may have
      its greatest impact on productivity losses, including increased absenteeism and
      short-term disability, higher turnover, and suboptimal performance at work.
      Although there is no conclusive evidence yet that physical health care costs
      decrease when depression is effectively treated, there is growing evidence that
      productivity improvements occur as a consequence of effective treatment, and
      those improvements may offset the cost of the treatment.

PMID- 11977419
TI  - Supervisors' attitudes toward return to work after myocardial infarction or
      coronary artery bypass graft.
AB  - Although workplace supervisors may play a significant role in the return-to-work
      process, there are very few scientific references to this effect. This study
      surveyed supervisors' reactions, attitudes, and anxieties concerning the return
      to-work of employees after myocardial infarction or coronary artery bypass graft.
      A total of 58 supervisors of employees who had returned to work responded to a
      self-report questionnaire based on interviews with occupational physicians and
      nurses, heart patients, and experienced supervisors. The supervisors believed
      they contributed significantly to the successful occupational rehabilitation of
      heart patients and emphasized the importance of ongoing consultations with
      occupational physicians. Yet many of the respondents considered such employees to
      be problematic to a considerable extent, because their occupational functioning
      is often impaired initially and special attention and support is required.

PMID- 11977420
TI  - Lung cancer and indoor exposure to coal and biomass in rural China.
AB  - Incomplete combustion of coal in homes has been linked with lung cancer in China.
      We report on a lung cancer case-control study in a rural area of China, where
      many residents live in underground dwellings and burn coal and unprocessed
      biomass (crop residues, wood, sticks, and twigs) for heating and cooking. We
      interviewed 846 patients with lung cancer (626 men, 220 women; aged 30 to 75
      years) diagnosed between 1994 and 1998, and 1740 population-based controls. The
      odds ratio for lung cancer associated with coal use compared with that for
      biomass in the house of longest residence was 1.29 (95% confidence interval, 1.03
      to 1.61), adjusted for smoking and socioeconomic status. The risk for lung cancer
      increased relative to the percentage of time that coal was used over the past 30
      years (P = 0.02). Our findings suggest that coal may contribute to the risk of
      lung cancer in this rural area of China.

PMID- 11977421
TI  - Acute traumatic occupational hand injuries: type, location, and severity.
AB  - The National Electronic Injury Surveillance System reports that the fingers and
      hand are the most frequent body parts injured at work and treated in hospital
      emergency departments. In this study, we describe the type, location, and
      severity of occupational hand injuries among 1166 patients recruited from 23
      occupational health clinics in five New England states. Subjects ranged in age
      from 18 to 77 years, with a mean of 37.2 years (SD, 11.4), and approximately 75%
      were men. In decreasing order of frequency, subjects were employed in machine
      trades, service work, structural work, and less frequently, in benchwork,
      professional, technical managerial and clerical, and sales work. The majority of
      subjects (83.4%) had a single type of injury: 62.6% were lacerations, 13.1% were
      crush injuries, 8.0% were avulsions, and 6.1% were punctures. Metal items, such
      as nails, metal stock, and burrs accounted for 38.4% of the injuries, followed by
      hand tools with blades and powered machinery (24.4% and 12.3%, respectively).
      Hand tools with blades were least likely to result in multiple types of injuries,
      whereas powered machines or nonpowered hand tools were more likely to result in
      multiple types of injuries than other injury sources. The generalizability of
      these results should be limited to clinic-based patients employed in similar
      occupations. The results of this study may suggest possible prevention strategies
      for acute traumatic hand injuries.

PMID- 11977422
TI  - Effects of occupational exposure to organophosphate pesticides on nerve and
      neuromuscular function.
AB  - This study aimed to investigate whether occupational exposure to organophosphate
      (OP) pesticides caused neurophysiological abnormalities. Thirty farmers who
      regularly spray OP pesticides and 30 fishermen (controls), living close by but
      not involved in pesticide spraying, were evaluated during and between cultivation
      seasons. The farmers had higher erythrocyte acetylcholinesterase levels than the
      controls during (P = 0.06) and between cultivation seasons (P = 0.09). During the
      cultivation season, there was a significant reduction in erythrocyte
      acetylcholinesterase activity in both groups (P < 0.01). Significant differences
      between the farmers and controls were found in sensory conduction velocity (P =
      0.04) and motor conduction velocity (P = 0.04) between cultivation seasons.
      Sensory conduction velocity was reduced significantly in farmers (P < 0.01) and
      in controls (P = 0.04) during the cultivation season. Effects of OP poisoning
      were seen both in farmers and in controls, who had no history of spray
      activities. Evidence of sensory dysfunction after acute exposure and sensory and
      motor impairment after long-term low-level exposure to OP was seen.

PMID- 11977423
TI  - Workforce participation by persons with disabilities: the National Health
      Interview Survey Disability Supplement, 1994 to 1995.
AB  - Using the National Health Interview Survey Disability Supplement of 1994 to 1995,
      we examined the factors associated with employment among Americans with
      disabilities. Persons with disabilities who were more educated were more likely
      to be working. Married men were more likely to work than unmarried men (odds
      ratio [OR], 1.58). Blacks were less likely to work than whites (OR, 0.56).
      Persons with disabilities related to cardiovascular disease (OR, 0.23),
      musculoskeletal disease (OR, 0.37), and respiratory disease (OR, 0.23) were less
      likely to work than other Americans with disabilities. Among persons with
      psychiatric disorders, there was considerable variety in the propensity to work.
      Persons with schizophrenia (OR, 0.24) and paranoid delusional disorder (OR, 0.34)
      were markedly less likely to work; persons with bipolar disorder (OR, 0.60) and
      major depression (OR, 0.69) were also less likely to work. Lastly, persons with
      self-reported alcohol abuse (OR, 1.30) were more likely to work, and persons with
      self-reported drug abuse (OR, 0.93) were not less likely to work, than others in
      our study population of Americans with disabilities.

PMID- 11977424
TI  - The effects of a medical care utilization review program on back and neck injury
      claims.
AB  - A number of quality-based evaluation and treatment protocols have been developed
      and marketed for the management of work-related musculoskeletal problems. Yet,
      little is known about their effectiveness in improving patient outcomes. We
      evaluated one such approach adopted by the Department of Labor and Industries,
      which insures approximately two-thirds of the non-federal workforce in Washington
      State. The outcomes of back and neck injury claims (primarily sprains and
      strains) filed in the 2 months after the program was fully operational were
      compared with two comparable groups of claims from the same base population filed
      before the program's availability. There were no statistically significant
      differences between groups in the number of days of work loss, medical costs, and
      permanent partial disability awards granted during the 2 years after injury. The
      quality-based program used as an adjunct to claims management failed to improve
      outcomes.

PMID- 11977425
TI  - Genetic polymorphisms of MnSOD, GSTM1, GSTT1, and OGG1 in coal workers'
      pneumoconiosis.
AB  - Little is known about the genetic susceptibility to coal workers' pneumoconiosis
      (CWP). We investigated the association between genetic polymorphisms of MnSOD,
      GSTM1, GSTT1, or OGG1 and susceptibility to CWP. The study population was
      composed of 259 Chinese retired coal miners who had similar dust exposure
      histories. Of these, there were 99 cases with International Labor Organization
      chest radiologic criteria for CWP and 160 controls (with no radiologic criteria
      for CWP). Individual dust exposure variables were estimated from work histories,
      and smoking information was obtained from interviews. Polymerase chain reaction
      based techniques evaluated the genotypes of all study subjects. There were no
      differences in genotype frequency of MnSOD, GSTM1, GSTT1, and OGG1 between miners
      with CWP and miners without CWP, by logistic regression analysis. Cumulative dust
      exposures, but not genetic polymorphisms, were associated significantly with the
      presence of CWP. This study illustrates the complexity of factors that may
      contribute to the development of CWP.

PMID- 11977426
TI  - Inhibitory and excitatory circuits of cerebral cortex after ischaemic stroke:
      prognostic value of the transcranial magnetic stimulation.
AB  - The motor cortex excitatory responses and inhibitory effects after transcranial
      magnetic stimulation were studied in 20 patients with hemiparesis after ischaemic
      stroke in the MCA territory within 24 hours from the beginning of the
      symptomatology, in order to evaluate prognostic utility of these techniques and
      to compare they with the conventional MEP examination. Central motor conduction
      time was abnormal in two patient. Ipsilateral cortico-cortical inhibition was
      decreased after stimulation of the ischaemic motor cortex in all patients; the
      duration of the silent period was prolonged in 15 patients, whereas the resting
      threshold for responses to magnetic stimulation was abnormal in 8 patients. Only
      this last finding was constantly associated with a poor motor recovery; therefore
      the patients with preserved motor threshold reached a good motor function in the
      following months. The motor cortex threshold measurement is easily performed and
      the most sensitive parameter in our group of patients with hemispheric infarct.
      Our study suggested that the evaluation of the modifications in the intrinsic
      excitatory properties rather than in the inhibitory cortical circuits may offer a
      prognostic tool for predicting functional outcome following ischaemic stroke.

PMID- 11977427
TI  - On the evaluation of muscle fiber conduction velocity considering waveform
      properties of an electromyogram in M. biceps brachii during voluntary isometric
      contraction.
AB  - The surface myoelectric signal during 20% maximum voluntary contraction was
      measured in m. biceps brachii using array electrodes for ten subjects in order to
      evaluate the distribution of muscle fiber conduction velocity (MFCV) in a whole
      muscle. MFCV was estimated by two calculating methods of the peak maximum method
      and the cross-correlation method from the myoelectric signals which were
      processed by techniques of the averaging and the non-averaging. It was found that
      the values of MFCV depended on the location irrespective of the kind of
      calculating method used and the kind of processing technique of myoelectric
      signal. In both the motor end-plate zone and the tendon zone, the values of MFCV
      showed more than 7.0 m/s. In the regions other than the motor end-plate zone and
      the tendon zone, the values of MFCV showed about 3.90 m/s which were almost
      constant. The statistical differences of the values of MFCV were in the same
      locations measured not recognized between the two calculating methods nor between
      the two processing techniques. In the cross-correlation method, the relation
      between MFCV and the electrode location was evaluated by both the maximum
      correlation coefficient and the amplitude ratio between the different neighboring
      channels to evaluate the conductive waveform properties of action potentials. The
      changes of parameters (i.e., MFCV, maximum correlation coefficient and amplitude
      ratio) depended on the electrode location. The values of MFCV significantly
      increased in the regions of the motor end-plate zone and the tendon zone, where
      the maximum correlation coefficient and amplitude ratio significantly decreased.
      The values of the coefficient of variance (CV) of three parameters in those
      regions were larger than those in other regions, i.e., the regions other than the
      motor end-plate zone and the tendon zone. A high maximum correlation coefficient
      and a high amplitude ratio were necessary for a reliable measurement of the MFCV.

PMID- 11977428
TI  - Normative values for high voltage electrical stimulation across the brachial
      plexus.
AB  - OBJECTIVES: To obtain normative values for High Voltage Electrical Stimulation
      across the brachial plexus between Erb's point, C8 root and T1 root. A case study
      of probable true thoracic outlet syndrome is used to illustrate the usefulness of
      the method. METHODS: 22 patients were tested for use in normative date pool with
      complaints unrelated to the ulnar nerve, the majority of which were pure carpal
      tunnel syndrome. High voltage stimulation was performed at Erb's point, C8 root
      and T1 root. Recording was from the abductor digit minimi muscle. RESULTS: Upper
      limit for absolute latencies were 13.9 ms, 14.5 ms and 14.5 ms for Erb's point,
      C8 root and T1 root stimulation respectively. Corresponding lower limits of
      amplitude were 4.8 mV, 3.4 mV and 2.9 mV. Upper limits for interpeak latencies
      were 1.4 ms and 1.2 ms for C8 to Erb's point and T1 to Erb's point respectively.
      In a case of true thoracic outlet syndrome, the symptomatic side revealed
      prolonged interpeak and absolute latencies. The asymptomatic side remained within
      normal limits. CONCLUSION: Normative values for high voltage stimulation across
      the brachial plexus are useful in cases of suspected compression in this proximal
      location of the upper limb.

PMID- 11977429
TI  - Assessment of motoneuron excitability using recurrent inhibition and paired
      reflex depression protocols: a test of reliability.
AB  - Motor output may be regulated by both pre- and post-synaptic mechanisms. The
      purpose of this study was to investigate the reliability of two measurement
      protocols, which purport to examine spinal mechanisms responsible for gating
      motoneuron excitability. Nine subjects (aged 29 +/- 5 years) were tested using
      two soleus H-reflex protocols; 1) recurrent inhibition (RI) and 2) paired reflex
      depression (PRD). The dependent variable for each protocol was the peak-to-peak
      amplitude of the conditioned Hoffmann reflex (H-reflex). Seven trials were
      obtained for each subject under each condition as well as control values to
      assess test-retest reliability. After all trials were collected the subjects
      rested for at least five minutes after which the process was repeated. Each
      subject returned to the lab after a period of no less than 24 hours at which time
      the process was repeated. Protocol #1: Control reflexes (20% of maximal motor
      response) were obtained during quiet stance. After obtaining control trials two
      reflex responses were elicited which were separated by 10 ms on each trial to
      assess recurrent inhibition (Pierrot-Deseilligny et al., 1976; Bussel and Pierrot
      Deseilligny, 1977). Protocol #2: Again a double-pulse technique was used to
      assess reflex activation history on motoneuron pool output (Trimble et al.,
      2000). This protocol utilized two reflex stimuli of the same intensity separated
      by 80 ms. The peak-to-peak amplitude of the control, RI conditioned and PRD
      conditioned H-reflexes exhibited intraclass reliability estimates of .97, .97 and
      .93 respectively. To achieve a reliability of rI > or = .80, it is recommended
      that a minimum of 2 trials be used for the RI protocol and that 4 trials be used
      for the PRD protocol. The results indicate that both techniques provide a means
      to objectively and reliably measure spinal mechanisms for gating motoneuron pool
      output.

PMID- 11977430
TI  - Quantitative surface EMG in the diagnosis of neuromuscular disorders.
AB  - This paper describes a non-invasive quantitative method for the diagnosis of
      neuromuscular disorders using surface EMG (sEMG). We found sEMG to be a reliable
      method that can be used to differentiate neuropathic and myopathic patients from
      the normal subjects. The multivariate discriminant analysis of sEMG data assisted
      in separating myopathic from neuropathic disorders. Nevertheless sEMG is not
      robust enough to replace needle EMG as a stand-alone diagnostic tool. However
      quantitative sEMG that is described in this paper could be adopted as a simple,
      rapid and non-invasive technique to be used in the out patients clinic by EMG
      naive clinicians as a screening method for neuromuscular disorders, before
      referring the patients for detailed clinical neurophysiological examinations.

PMID- 11977431
TI  - Visual evoked potential & brainstem auditory evoked potentials in acute attack &
      after the attack of migraine.
AB  - PURPOSE: To study the effect on visual evoked potential (VEP) and brainstem
      auditory evoked potential (BAEP) at time of acute attack and after 7 days of the
      attack of migraine. MATERIAL AND METHODS: We studied BAEP and pattern reversal
      VEP in 25 patients during acute attack and after 7 days of the attack. The
      diagnosis of migraine was established according to criteria given by
      international headache society (IHS). Peak and interpeak latencies (IPL's) of
      BAEP and P100 latency of VEP were the main criteria to judge abnormalities.
      RESULTS: There were prolonged peak and interpeak latencies in BAEP and prolonged
      peak latency (P100) in VEP at the time of acute attack of migraine. The data of
      these abnormal recording were highly significant. After 7 days when the attack
      was over, we recorded the BAEP and VEP again. The observation obtained at this
      time was comparable to normal values. CONCLUSIONS: From the observation of this
      study we can safely conclude that in acute attacks of migraine there may be some
      pathological changes in different areas of brain and brainstem, producing changes
      in evoked potential which are statistically highly significant. However, these
      changes are reversible, as the values of BAEP & VEP on 7th day after the attack
      were comparable to those observed in normal healthy control.

PMID- 11977432
TI  - Sympathetic skin response in diabetic neuropathy.
AB  - Autonomic neuropathy is a complication of diabetes mellitus (DM) in substantial
      proportion of cases and may cause definite autonomic symptoms. Because
      conventional electrophysiological methods do not assess the autonomic nervous
      system, simple reproducible tests were developed. One of them is sympathetic skin
      response (SSR) which provides useful information about the status of sympathetic
      postganglionic function. The aim of this study is to perform SSR in diabetic
      patients to see whether this test can be used as an electrophysiological method
      for the diagnosis and confirmation of diabetic autonomic neuropathy. 20 diabetic
      patients who had electrophysiologically confirmed polyneuropathy but showed no
      symptoms or signs referable to autonomic system dysfunction were included. 14
      (70%) patients demonstrated abnormal SSR. 2 abnormal patterns were observed. An
      absent response in at least one tested lower extremity (50%) and prolonged foot
      with normal hand latency (20%). 6 patients (30%) demonstrated no abnormalities.
      Foot and hand latencies in diabetics did not differ significantly from those of
      normal controls (p: 0.4, p: 0.1) and no correlation could be found with latencies
      and duration of sickness, patient's age and HbA1c values. We believe latency
      measurement is an objective measure of conduction in multineural pathways and can
      detect subclinical involvement of sympathetic nervous system in diabetics who do
      not manifest symptoms or signs referable to autonomic system dysfunction.

PMID- 11977433
TI  - The effect of the occlusal splints on the treatment of temporomandibular
      disorders--a computerized electromyographic study of masseter and anterior
      temporalis muscles.
AB  - The effect of the occlusal splints on the treatment of temporomandibular
      disorders--a computerized electromyographic study of masseter and anterior
      temporalis muscles. The comprehension of the determinant factors of
      temporomandibular disorders is still inconclusive, since that the etiology is
      associated with multidisciplinary knowledge. The purpose of this study was to
      evaluate the effectiveness of the therapy with occlusal splints in patients with
      temporomandibular disorders by the computerized electromyography. It was selected
      twenty-two patients with signs and symptoms with changes of the stomatognathic
      system, males and females patients, with ages between 18 and 53 years old. Plane
      occlusal surface splints were constructed in acrylic resin and placed in each
      patients. Electromyographic evaluations of masseter and anterior temporalis
      muscles were performed during the mandibular isometric clenching before inserting
      and after 90, 120 and 150 days of using the occlusal splints. After 90 and 120
      days of using them, they were changed by canine guidance and group function
      respectively. The results after the polynomial regression analysis showed that
      there were significant reductions (p < 0.05) in the electromyographic activity
      along the entire period of treatment during the mandibular isometric clenching
      for masseter and anterior temporalis muscles. The group function showed a shorter
      eletromyographic activity for both muscles.

PMID- 11977434
TI  - Expressions of Holocaust experience and their relationship to mental symptoms and
      physical morbidity among Holocaust survivor patients.
AB  - This study explores current expressions of past trauma among Holocaust survivors.
      Medical records and extensive interviews were analyzed for 38 Holocaust survivors
      who were hospitalized and/or under ambulatory care. The sample consisted of 55%
      women and 45% men whose mean age was 72 (SD = 9.2). Expressions of Holocaust
      experience yielded two factors: Holocaust-as-Present (e.g., feeling the Holocaust
      experience as continuing, Holocaust-related somatization) and Holocaust-as-Past
      (e.g., avoiding preoccupation with traumatic memories, feeling unduly stigmatized
      as a survivor). The results indicate that mental symptoms and the number of
      medical diagnoses are positively correlated with Holocaust-as-Present but
      negatively correlated with Holocaust-as-Past. However, scoring high on Holocaust
      as-Past relates to a higher danger to life as a result of significant morbidity.
      The findings suggest two differential modes of either remaining enmeshed in the
      traumatic experience or attempting to contain the sequelae of the trauma. These
      modes differ in their implications for mental and physical health.

PMID- 11977435
TI  - Clinical significance and predictors of treatment response to cognitive-behavior
      therapy for insomnia secondary to chronic pain.
AB  - We examined individual responses to cognitive-behavior therapy for insomnia in 51
      persons with chronic pain to determine the rate of clinically significant change
      and to identify predictors of successful treatment response. Outcome measures
      consisted of the Pittsburgh Sleep Quality Index (PSQI) and diary measures of
      sleep latency and sleep continuity. Using reliable change indices, 57% of
      participants were statistically improved on the PSQI after 7 weeks of treatment,
      but only 18% were considered fully recovered from their sleep problems. No
      demographic variables predicted treatment response but persons who reliably
      improved on the PSQI had a lower sleep self-efficacy at baseline. Improvers
      showed a significant increase in sleep self-efficacy ratings and a decrease in
      self-reported levels of distress and pain-related disability. These results
      suggest that patients with insomnia secondary to chronic medical conditions can
      be helped with cognitive-behavior therapy, although most individuals continue to
      have mild or subthreshold sleep problems at posttreatment.

PMID- 11977436
TI  - The Fear of Pain Questionnaire-III: further reliability and validity with
      nonclinical samples.
AB  - The Fear of Pain Questionnaire-III (FPQ-III) is a 30-item self-report measure
      designed recently to assess fears about pain across three pain dimensions:
      severe, minor, and medical. We conducted three studies to replicate the factor
      structure of the FPQ-III and examine several psychometric properties of
      reliability and validity in nonclinical samples. A principal-axis with oblique
      rotation analysis provided strong empirical support for the three-factor solution
      of the FPQ-III (Study 1). In Study 2, results of the confirmatory factor analyses
      (CFA) confirmed the fit of the three-factor oblique model to an independent
      sample of data. In addition, we evaluated several measurement models to address
      issues related to convergent and discriminant validity for the FPQ-III. In Study
      3, data from adult samples were analyzed for the adequacy of internal consistency
      and criterion-related validity of the FPQ-III. The FPQ-III total and scales
      showed high levels of reliability estimates across the three studies. Limitations
      and future research with the FPQ-III are discussed.

PMID- 11977438
TI  - Effects of a detailed sexual behavior interview on perceived risk of HIV
      infection: preliminary experimental analysis in a high risk sample.
AB  - Effects of the HIV-Risk Timeline Followback Interview (TLFB), which uses detailed
      memory cues to assess retrospectively sexual behavior and substance use on a day
      by-day basis, on HIV risk-reduction motivation were tested. Thirty-four adults
      (76% male, 100% African American) were randomly assigned to three interview
      conditions: (a) HIV-Risk TLFB Interview, (b) 27 sexual behavior frequency
      questions, and (c) diet and nutrition using the TLFB format. Participants
      completed measures of HIV risk-reduction motivation immediately before and after
      the experimental assessment component. The a priori hypotheses that the HIV-Risk
      TLFB group would exhibit greater increases on indices of HIV risk reduction
      motivation than participants in either of the other two groups and that
      participants in the nutrition interview condition would exhibit greater increases
      in motivation for dietary improvement were supported, indicating that
      participating in detailed health behavior interviews, but not cursory
      assessments, may lead to increased motivation for behavior change.

PMID- 11977437
TI  - The PedsQL 4.0 Generic Core Scales: sensitivity, responsiveness, and impact on
      clinical decision-making.
AB  - The PedsQL 4.0 (Pediatric Quality of Life Inventory) Generic Core Scales are
      child self-report and parent proxy-report scales developed to measure health
      related quality of life (HRQOL) in children and adolescents ages 2-18. The PedsQL
      4.0 Generic Core Scales consist of 23 items applicable for healthy school and
      community populations and pediatric populations with acute and chronic health
      conditions. The 4 PedsQL 4.0 Generic Core Scales (Physical, Emotional, Social,
      School) were administered to 209 children and 269 parents (289 subjects accrued
      overall) recruited from pediatric cardiology, orthopedics, and rheumatology
      clinics. Sensitivity, responsiveness, and the impact on clinical decision-making
      were determined. The PedsQL was differentially sensitive to increasing degrees of
      cardiac disease severity in the cardiology clinic setting and responsive to
      clinical change over time in the pediatric orthopedics clinic setting. In the
      pediatric rheumatology clinic setting, the PedsQL demonstrated an impact on
      clinical decision-making, resulting in subsequent increases in HRQOL.

PMID- 11977439
TI  - Fatigue severity, attributions, medical utilization, and symptoms in persons with
      chronic fatigue.
AB  - This study examined the roles of ethnicity, gender, and socioeconomic status
      (SES) in predicting fatigue severity, symptoms, medical utilization, and
      attributions among a sample of individuals with chronic fatigue. Using path
      analysis, a model was tested and revised. In the new model, gender predicted
      fatigue, ethnicity predicted attributions, fatigue predicted medical utilization
      and attributions, and attributions predicted medical utilization. Women reported
      more fatigue and were more likely to feel that stress and depression were causing
      their fatigue. Higher-SES participants were more likely to cite stress and
      overwork as causing their fatigue. Latinos reported more physical symptoms than
      African Americans and Whites. The implications of these results are discussed.

PMID- 11977440
TI  - [Optoelectronic display system for minimal invasive laparoscopic operations:
      initial experiences with new face-mounted display video eyeglasses].
AB  - A major aspect of efforts to improve minimally invasive surgery is the
      optimization of visualization, which is currently unsatisfactory due to the
      limited number of pixels in the monitors used, and inadequate alignment of the
      optical axis. Optical systems provided with commercially available head-mounted
      displays have failed to improve optical quality and significantly facilitate or
      improve laparoscopic surgery [2,3]. Innovations in the field of consumer video
      using a new optical prism and a high-resolution matrix (180,000 pixels) are the
      core elements of a new face-mounted display (FMD-Eye-Trek 700, Olympus Optical
      Co, Europe GmbH, Hamburg, Germany) that provides high image quality. This device
      has now been tested for the first time during laparoscopic procedures (n = 14)
      and combined laparoscopic-endoscopic procedures (n = 7) under clinical
      conditions. Impressive optical, ergonomic and surgeon-related benefits were
      established.

PMID- 11977441
TI  - [Piezoresistive sensors for medical applications exemplified by a probe for
      measure pressure in the rectum].
AB  - We described a pressure sensor probe suitable for assessing dynamic rectal
      pressure profiles. It comprises 10 piezoresistive sensors mounted in low
      temperature co-fired ceramic. To protect against corrosion, the sensors are
      coated with a biocompatible silicone elastomer. The ceramic measures 4.5 x 5.5 x
      1.4 mm. The entire probe has a diameter of 9 mm and a length of 20 cm. A healthy
      test subject was submitted to rectal manometry. The experimental data and
      analysis of linearity, hysteresis errors, temperature dependence and
      reproducibility are discussed. The sensor probe extends classical anorectal
      manometry, in particular with regard to the diagnosis of rectal motility
      disorders.

PMID- 11977442
TI  - [Development of an optical 3-D position measuring system for simultaneous
      detection of 6 degrees of freedom].
AB  - A few years ago it became possible to carry out complicated surgical procedures
      in humans with the required precision by combining medical imaging (MRI, CT) with
      minimally invasive surgery. The confined space within these imaging systems and
      the resulting inaccuracies associated with the manual use of instruments
      increasingly make necessary the help of aids ranging from positioning systems to
      robotic devices, which themselves must be position controlled. A position sensor
      has been developed for a medical robotic system allowing the image-controlled
      insertion of injection needles and the simultaneous administration of different
      drugs. The 3D position coordinates are determined by a noncontact optical
      principle, which also enables simultaneous determination of all 6 basic degrees
      of freedom of the robotic system (3 translational, 3 rotational). On the basis of
      an area image sensor and the measurement of a geometrically defined structure in
      the path of the rays between sensor and light source, the position coordinates
      are calculated almost real time. Special emphasis was placed on designing the
      sensor system to cover a sufficiently large workspace to enable it to cover the
      entire intervention area. The sensor described herein determines the position
      coordinates in a volume of 10 x 10 x 10 cm at a resolution of up to 1 mm for
      translations and 1 degree for rotations.

PMID- 11977443
TI  - The grading of normal pressure hydrocephalus.
AB  - PATIENTS AND METHOD: During a period of 15 years we investigated 200 patients
      suspected of normal pressure hydrocephalus (NPH) by means of an intrathecal
      infusion test. In 107 patients (54%) the diagnosis of a normal pressure
      hydrocephalus could be confirmed. For the evaluation of the course of disease we
      used the Black-Grading-Scale for shunt assessment [1] and the clinical grading
      for chronic hydrocephalus (Kiefer-scale) [4] pre- and postoperatively as well as
      in a follow-up examination seven months after surgical treatment. The aim of our
      study was to find out a quick and easy-to-handle bed-side examination for the
      grading of NPH. DISCUSSION: The Black-Grading-Scale does not allow to distinguish
      between patients in an unchanged condition and those with a worsening of their
      symptoms. Therefore this scale is useful for patients with an obstructive
      hydrocephalus but not for those with a NPH. In our opinion the clinical grading
      of Kiefer [4] seems to be the most reliable scale for the grading and long term
      follow-up of a normal pressure hydrocephalus. CONCLUSION: Our own created NPH
      Recovery-Rate is based on the clinical grading for chronic hydrocephalus (Kiefer
      scale) [4]. It allows the interindividual comparison between the courses of
      disease in patients with normal pressure hydrocephalus.

PMID- 11977444
TI  - Transformation of whole-head MEG recordings between different sensor positions.
AB  - In this work, a method is presented for the transformation of MEG recordings to a
      standard sensor position. For the case of an 148 channel magnetometer array, the
      algorithm was evaluated using simulations as well as phantom head recordings. It
      turned out that the method is very robust and yields accurate results regardless
      of the position of the field generator, even with large differences between
      original and standard (target) sensor positions and high noise. The method can be
      applied as a prerequisite for comparing or averaging recordings of different
      subjects or sessions.

PMID- 11977445
TI  - [The HEPFIEx simulator, a device for determination of friction between femur head
      prosthesis and cartilage].
AB  - We describe a device designed to investigate friction between various femoral
      head prostheses and human acetabula. It enables not only the determination of
      friction and the relevance of the play between the femoral head and acetabulum,
      but also the evaluation of the kinematic behaviour of bipolar prostheses. In the
      simulator, the various femoral head prostheses are placed on a special cone and
      tested against a human cadaveric acetabulum. The swiveling range of the device is
      uniaxial, and the swiveling angle is +/- 35 degrees. The maximum force produced
      pneumatically is 5kN. Testing of the simulator with a TEP was successful and
      friction-coefficients of < 0.1 were measured, as are reported in the literature.

PMID- 11977446
TI  - [Ibuprofen for Alzheimer's?].

PMID- 11977447
TI  - [A scenerio for virus infection].

PMID- 11977448
TI  - [World-wide sales power of a drug group! The evolution of antipyretic
      analgesics].

PMID- 11977449
TI  - [How do aspirin and company work? Cyclooxygenases--point of attack of
      nonsteroidal antirheumatics].

PMID- 11977450
TI  - [A heterogenous drug class. NSAID: classification and spectrum of action].

PMID- 11977451
TI  - [Traditional use of proven drugs. The importance of botanical antirheumatics].

PMID- 11977452
TI  - [What's in the future? New NSAIDs].

PMID- 11977453
TI  - [The power of packaging. NSAID: concepts for dosage form optimization].

PMID- 11977454
TI  - [Current post-marketing information. Effects and adverse effects of celecoxib].

PMID- 11977455
TI  - [Specificity, action, indications and safety. Criteria for the use of COX-2
      inhibitors].

PMID- 11977456
TI  - [Penetration rate and action. Percutaneous topical administration of NSAIDs].

PMID- 11977457
TI  - [Can we treat with modern antirheumatics? Costs of NSAID treatment].

PMID- 11977458
TI  - [Human costs of tobacco dependence].
AB  - Human costs are an indicator of the value attributed to human burden related to
      diseases. The present paper summarizes a Swiss study. led by economists and
      physicians, which estimate the monetary value attributed by the general
      population regarding the consequences on quality of life of smoking related
      diseases. Such economic study may contribute to better understand smokers'
      concerns and beliefs and to improve effective strategies for smoking cessation in
      primary care.

PMID- 11977460
TI  - [Secret and protection of personal data in the medical field].

PMID- 11977459
TI  - [For a non-reductionist approach to hyperactivity in children].

PMID- 11977461
TI  - [The secret, let's talk about it!].
AB  - Medical secret, as other professional secrets, is highly suspected in a society
      witch emphasis communication about all. This article tempts to understand why
      this appears.

PMID- 11977462
TI  - [Hommage to Professor Jacques Bergier].

PMID- 11977463
TI  - [Ready-to-eat food: a simple way to healthy cooking].

PMID- 11977464
TI  - [Medecine & Hygiene--Revue Medicale de la Suisse Romande: the same battle!].

PMID- 11977465
TI  - [Cystic lesions of the pancreas: towards a standardized diagnostic approach?].

PMID- 11977467
TI  - [Food allergy and cross-reactions].

PMID- 11977466
TI  - [Epidemiology of anal incontinence].

PMID- 11977468
TI  - [Bell's palsy: idiopathic or infectious?].
AB  - Bell's palsy (BP), is a disease of unknown etiology; it's thought to be
      idiopathic, although it seems to be linked with infections, in particular viral
      ones. Within three weeks, three cases of BP were admitted to our hospital. The
      investigations suggested different causes: Herpes simplex virus infection,
      neuroborreliosis and the side effect of an influenza vaccine. Based on the
      literature, guidelines were established for the diagnostic evaluation and
      management of cases of BP in our hospital. Criteria for cerebral radiologic
      imaging procedures and laboratory investigations are discussed. We propose
      therapeutic strategies adapted to the probable cause of BP. In conclusion BP is
      associated with several distinct disease entities and the description of Sir Bell
      in the XIXth century appears outdated. In any case of BP the aim should be to
      find a specific etiology in order to give appropriate treatment.

PMID- 11977469
TI  - [Dementia syndrome of affective and psychotic origin in the elderly: illustration
      with clinical cases].
AB  - The aetiological diagnosis of dementia in the elderly is dominated by the search
      for curable organic factors. With the exception of drug-induced disorders the
      treatment of organic factors only seldom leads to reversal of the dementia
      syndrome. On the other hand, approximately 10% of all dementia syndromes in the
      elderly are due to psychiatric conditions, most often affective and psychotic
      disorders. The main differential diagnosis is with a degenerative disease. Thus,
      a false diagnosis may have tremendous consequences. The diagnosis of a
      degenerative dementia suggests a universally serious prognosis for both the
      patient and their family. The diagnosis of a dementia syndrome due to a
      psychiatric disorder implies specific pharmacological and nonpharmacological
      interventions and is accompanied by a different and clearly more favorable
      prognosis than degenerative disorders. The clinical vignettes presented in this
      article help discuss the clinical features of the dementia syndromes due to
      psychiatric disorders and are intended to draw the GP's attention to the
      psychiatric aetiology in some demented patients.

PMID- 11977471
TI  - Physician's Health Committee. Arkansas Medical Foundation Report.

PMID- 11977472
TI  - Arkansas State Medical Board Report.

PMID- 11977473
TI  - CME Accreditation Committee Report.

PMID- 11977470
TI  - [Human burden and human costs of diseases].

PMID- 11977475
TI  - Arkansas Department of Health Report.

PMID- 11977474
TI  - Arkansas Health Care Access Foundation Report.

PMID- 11977477
TI  - When good docs go bad: the impaired physician.

PMID- 11977478
TI  - The medical family under siege: where can physician families find the support
      they need? De novo!

PMID- 11977479
TI  - The university of health sciences: leading in medical education.

PMID- 11977480
TI  - Substance abuse and dependence in physicians: the Missouri Physicians Health
      Program--an update (1995-2001).
AB  - Substance abuse and dependence (alcohol and drugs) are behavioral disorders and
      treatable medical diseases. There is growing concern in the medical community for
      physicians impaired by these diseases. The Missouri Physicians Health Program has
      been established to help impaired physicians return to healthy personal and
      professional lives. This confidential voluntary program of early referral,
      intervention, treatment, monitoring, and advocacy has been highly successful. The
      recovery rate in this study of 168 participants was 89%. New concepts of the
      "Behaviorally Disruptive Physician" and the Joint Commission on the Accreditation
      of Health Care Organization requirements regulating physician impairment are also
      discussed.

PMID- 11977481
TI  - A new team: the Missouri Physicians Health Program and the Joint Commission on
      the Accreditation of Health Care Organizations' new standard on physician health.

PMID- 11977482
TI  - The impaired physician: the role of the state board of healing arts.

PMID- 11977483
TI  - Cardiac manifestations of the antiphospholipid antibody syndrome: a review.
AB  - The antiphospholipid antibody syndrome (APLAS), though an uncommon entity
      involves multiple organs in the body. The antiphospholipid antibodies (APLA)
      refer to several groups of autoantibodies against negatively charged
      phospholipids occurring independently or in association with systemic lupus
      erythematosus (SLE) and related autoimmune disorders. Several studies to date
      found those patients with APLA, predominantly IgG and to lesser extent IgM
      isotype and lupus anticoagulant (LAC) are associated with arterial and venous
      thrombosis, recurrent fetal loss, thrombocytopenia, and livedo reticularis. We
      have described two cases of APLAS, one primary and the other secondary, their
      management and cardiac manifestations. Cardiac manifestations of the syndrome
      include coronary artery thrombosis and valvular heart disease. These can be
      serious and difficult to treat. Although the exact treatment of the cardiac
      manifestations of APLAS is not clear, anticoagulation is the currently
      recommended therapy.

PMID- 11977484
TI  - [Tuberculosis in the first semester 2001].

PMID- 11977485
TI  - [Considerations upon diagnosis and treatment of lung and pleural tumors in Mures
      county].
AB  - We studied 171 patients with pulmonary and pleural tumours, in 1999. Within this
      group we had 87.7% primary lung cancers, 8.8% pulmonary methastatic tumors and
      3.5% pleural mesothelioma. The primary lung cancer is more frequent in men (male
      female ratio = 8.4) and in patients living in rural area; it involved persons
      over 40 years only. The chronic tobacco use is the main risk factor we found
      among these patients (80%). All the patients showed symptoms linked to delayed
      diagnosis. Radiology was characteristic in 100% of the cases, showing typical
      aspects of lung tumours and complications and contributed to staging. The
      bronchoscopy was the main procedure in diagnosis (80.1%), allowing the
      microscopic confirmation and contributing in staging. The thoracic computed
      thomography was performed in 30.4% of the cases. We had a late case finding
      (56.7% in the stage III, 26% in the stage IV) allowing the surgical treatment in
      only 15.2% of the cases. The early diagnosis of lung cancers would be possible by
      "oncological screening", combining clinical aspects with data from radiology and
      bronchoscopy in high-risk persons (heavy smokers, contacts with cancer producing
      substances). Performing bronchoscopy and computed tomography in all patients with
      lung cancer would allow the histological diagnosis and the proper staging for a
      proper treatment. The education against smoking will allow the decrease of the
      lung cancer in the future.

PMID- 11977486
TI  - [The study of the frequency and features of bacteria isolated in patients with
      non-tuberculosis respiratory disorders admitted in "M. Nasta" Institute in the
      first trimester 2001].
AB  - The aim of this study was to determine the spectrum of bacteria isolated in
      patients with non-TB respiratory disorders, in order to find the frequency of
      germs isolated globally and in each of the 6 clinical syndromes: suppurations,
      chronic obstructive diseases exacerbations (COPD, bronchial asthma),
      pneumopathies, post-TB syndromes, tumors and interstitial lung diseases. We found
      the greatest global frequency in anaerobes (35%). This is in concordance with the
      high frequency of broncho-pulmonary suppurations (51% of the cases studied). In
      second place comes Ps. aeruginosa (18%), followed by Str. Pneumoniae (16%), H.
      influenzae (11%) and Klebsiella pn. (10%). Considering the germs identified in
      the various clinical syndromes, we found a high frequency of anaerobes associated
      to suppurations (51%), interstitial lung diseases (43%) and tumors (37%), while
      Ps. aeruginosa is first in post-TB syndromes (50%) and COPD exacerbations (21%),
      equal to H. influenzae. In pneumonias, Str. Pneumoniae was most frequently
      isolated (38%) followed by H. influenzae (25%). The susceptibility testing of
      strains of Klebsiella and Ps. aeruginosa revealed the increasing tendency to
      resistance to broad spectrum antibiotics, especially for Ps. aeruginosa, with
      consecutive difficulties in finding the appropriate treatment.

PMID- 11977487
TI  - [Prophylactic measures in tuberculosis hotbeds].
AB  - Starting with the premise of preventing tuberculosis by watching the
      epidemiological succession (earliest discovery and medical attendance of new
      cases, interception of the transmitting ways by annihilating the hotbed and
      measures taken for the contacts, strengthening the specific resistance by the BCG
      vaccination and sanitary education) we have analyzed the application of these
      measures in adult cases, both bacteriologically confirmed (M+C+, M-C+) between
      1995-2000 and found in those 280 contact children after the epidemiological
      investigation in Cluj-Napoca. The TSS/DOTS correctly and completely applied, no
      matter the place of application (hospital or ambulatory treatment) has drawn to a
      75% rate of healings and debacillations in adults and to over 90% in children.
      Chronics and deaths have been registered in adults only through unconformity to
      treatment (failure + abandon + lost). The measures applied to the contacts were
      correct, finding out children with only the benign type of tuberculosis and,
      exceptionally only, (1%) with more severe forms, no deaths being registered in
      this period. The measures applicable to the home hotbed, the sanitary education
      as well as the protective measures of the sanitary medical staff, employed to
      supervise and control tuberculosis admits improvement still being far from the
      theoretic ideal.

PMID- 11977489
TI  - [Invasive pulmonary aspergillosis].

PMID- 11977488
TI  - [Vaccines--their role and implications in respiratory pathology].

PMID- 11977490
TI  - [Association of atypical pulmonary TB, polyserositis, severe leukopenia and
      panniculitis. Case report].
AB  - Many reports have associated tuberculosis with haematological abnormalities.
      These reports suggest that severe pulmonary tuberculosis, if associated with
      reduced tissue cellular reaction, may cause blood discrasias. Anemia was present
      in 32 percent of patients. Leucopenia with neutropenia and lymphopenia was
      observed in 15 percent in patients with very severe clinical tuberculosis. Active
      tuberculosis was associated with significant reductions in absolute numbers of
      total T, T4 and B lymphocytes, but there were no significant differences in total
      T8 counts. T4 lymphopenia causes reversal of T4/T8 ratio. Also, many
      histopathologic diagnosis of panniculitis have been reported in tuberculosis
      patients--the incidence of panniculitis caused by tuberculosis was 8.2%. We
      present a case of secondary pulmonary tuberculosis with atypically Rx changes,
      associated with polyserositis and severe leucopenia, which debuted with a
      panniculitis.

PMID- 11977491
TI  - [Pulmonary involvement in polymyositis, case report].
AB  - The author report 1 case of myositis associated with pulmonary lesions. It was
      particularly difficult to diagnose, the patient serum was positive for the anti
      Jo1 antibody. This case have encouraged the authors to review the literature with
      particular attention to the diagnostic, the latest physiopathological data and
      the therapeutic basis of the pulmonary lesions with polymyositis and
      dermatomyositis.

PMID- 11977492
TI  - [Diagnosis of diseases of the trachea and main bronchi].

PMID- 11977493
TI  - [Image of limited transparency: what is your diagnosis?].

PMID- 11977495
TI  - [Smoking, oxidative stress and Pycnogenol].

PMID- 11977494
TI  - [Management of parapneumonic pleural effusion].

PMID- 11977496
TI  - [Aspects of the endemic evolution of tuberculosis in Bucharest in 2001].

PMID- 11977497
TI  - [Clinical and therapeutical correlations in Moraxella catarrhalis respiratory
      infection in children].
AB  - In childhood recurrent respiratory infection with Moraxella catarrhalis have high
      incidence demonstrated by multiple risk factors association (atopia,
      immunsuppresion, chronic diseases, malnutrition) that makes this common bacteria
      pathogen. The study was carried on 56 children (0-16 years old). Authors try to
      find correlations between clinical signs and microbiological markers that
      determine recurrent respiratory infection with Moraxella catarrhalis. Treatment
      consisted of association between "target" antibiotherapy and immunomodulation
      drugs. Efficacy of this treatment was proven by decreased numbers of recurrent
      infection (in 35% cases comparing to 53% selected cases for immunomodulation),
      improvement of evolution of chronic diseases, decreased number of days and price
      of hospitalisation.

PMID- 11977498
TI  - [Post-rifampicin acute renal failure--serious, but seldom recognized complication
      of the anti-tuberculosis treatment].
AB  - Post-rifampicin (RMP) acute renal failure (ARF) is a complication seldom
      recognized of the antiTB treatment worldwide. The renal failure which occurs
      especially after intermittent administration of RMP is most frequent due to acute
      interstitial nephritis by allergic mechanism. In our study we found very few
      cases of acute tubular necrosis or glomerular lesions revealed by rapidly
      progressive glomerulo-nephritis or nephrotic syndrome. The renal lesions,
      accompanied by anuria and usually needing hemodialysis, were associated to auto
      immune hemolytic anemia, trombocytopenia, hepatic failure and gastro-intestinal
      disturbances. The authors review their experience (60 cases), representing about
      half of the cases published worldwide. The main causes of this high prevalence of
      post-RMP ARF in Romania are discussed: intermittent twice-a-week RMP treatment,
      high incidence of TB, lack of compliance to treatment, possible contribution of
      some by-substances in RMP capsule. We described the clinic, biology and evolution
      of this dangerous and underestimated entity. We compared our experience with the
      published data, discussing the etiology and pathogenesis, trying to design the
      fine portrait of this ailment.

PMID- 11977499
TI  - Chronic alcoholics' knowledge regarding tuberculosis.
AB  - INTRODUCTION: CA are under high risk of developing active TB, very extended forms
      of TB (with possible lethal outcome) etc. AIM: To investigate CA's KN and social
      stigmatization (ST) regarding TB. METHOD: A questionnaire with 22 items (general
      KN, ST) completed by 115 CA treated for chronic alcoholism on the ward of
      psychiatry during the year 2000: 97% male, 74% aged 26-45 years, 62% urban,
      education level (low-35%, middle-59%, high-6%), 8% refugees, 79% smokers.
      RESULTS: 72% know that TB mainly affects the lungs, 75% that TB can be cured, 79%
      that there is a vaccine against TB, 57% that blood in the sputum is not the only
      symptom of TB, 22% that there is a connection between TB and AIDS, 33% that there
      are forms of TB which cannot be cured by standard anti-TB treatment (rural, lower
      educated/urban, middle educated CA: p = 0.03). 19% would not visit a close friend
      suffering from TB, 26% would prevent their child from marrying someone who
      suffered from TB, only 80% would not divorce their spouse if he/she suffered from
      TB (rural, lower educated/urban, middle educated CA: p = 0.005). Only 35% of the
      sample know that CAs are under higher risk of developing TB than the general
      population. CONCLUSIONS: 1. KN on TB is not sufficient among CAs. 2. ST of TB is
      high among CAs. 3. Health education of CAs during hospital treatment must
      include: information on the danger of tobacco, on the natural history of TB, on
      high risk of developing TB, on the importance of early self referral when
      suspected TB symptoms appear, on personal and community related responsibility of
      each human being regarding TB.

PMID- 11977500
TI  - [Pulmonary hypoplasia--etiopathology aspects].

PMID- 11977501
TI  - [Nontuberculous mycobacterial infections].

PMID- 11977502
TI  - [Tracheomalacia and secondary tracheopatia osteocondroplasica - a case report].
AB  - Tracheomalacia is a condition of the neonatal and infant airway, characterized by
      weakness of the supporting tracheal cartilage and widening of the posterior
      membranous wall. Together, these factors cause tracheal collapse, especially
      during times of increased airflow. The diagnosis of major airway collapse depends
      upon an accurate history combined with proper endoscopic evaluation.
      Tracheomalacia can be caused by a diffuse process of congenital origin or by a
      localized abnormality. The cases of acquired tracheomalacia occur with increasing
      frequency both in children and adults and are often not clearly recognized. These
      lesions may result from indwelling tracheostomy and endobronchial tube, chest
      trauma, chronic tracheobronchitis, inflammation (relapsing polychondritis),
      secondary to pulmonary resection, tracheal malignancy (cylindroma), and
      idiopathically. We present the case of a 59 years old male with acquired
      tracheobronchomalacia, associated with tracheopatia osteochondroplasica,
      secondary to COPD and a chronic parenchimal infection, on a diabetes mellitus
      type II background.

PMID- 11977503
TI  - [Why not to smoke?].

PMID- 11977504
TI  - [Mometasone furoate: a corticosteroid that simplifies asthma management].

PMID- 11977505
TI  - [What is your diagnosis? What is the appropriate attitude?].

PMID- 11977507
TI  - [First step in the introduction of the GOLD program in Romania].

PMID- 11977506
TI  - [Passive smoking and its implications].

PMID- 11977508
TI  - Treatment of infantile morbid night crying by acupuncture at Zhongchong point in
      100 cases.

PMID- 11977509
TI  - Observation on the therapeutic effect of Shu Feng Huo Luo Pian for treatment of
      osseous arthritis.
AB  - OBJECTIVE: To evaluate the therapeutic effect of Chinese patent drug Shu Feng Huo
      Luo Pian ([symbol: see text] Pill for Dispelling Wind and Activating Collaterals)
      for the treatment of osseous arthritis. METHOD: 50 cases of osseous arthritis
      were divided randomly into two groups, the Shu Feng Huo Luo Pian group (the
      experimental group), including 30 cases (aged 63.5 +/- 4 years), treated with 2
      such pills, p.o., bid; and the control group, including 19 cases (aged 63 +/- 5
      years), treated with Sulindac 0.2 g, p.o., bid. The two groups were all
      supplemented by medication of calcium Caltrate D 0.6 g, p.o., qd. The above
      mentioned medications were administered for 2 courses, 2 weeks constituting a
      course. RESULT: The total effective rate of the experimental group evaluated by
      the doctors was 83.3%, and that evaluated by the patients was 90%, with mild side
      effects. CONCLUSION: Shu Feng Huo Luo Pian is an effective Chinese patent drug
      for treating osseous arthritis, with less and mild side effects.

PMID- 11977510
TI  - Effect of acupuncture on the auditory evoked brain stem potential in Parkinson's
      disease.
AB  - Under the auditory evoked brain stem potential (ABP) examination, the latent
      period of V wave and the intermittent periods of III-V peak and I-V peak were
      significantly shortened in Parkinson's disease patients of the treatment group (N
      = 29) after acupuncture treatment. The difference of cumulative scores in
      Webster's scale was also decreased in correlation analysis. The increase of
      dopamine in the brain and the excitability of the dopamine neurons may contribute
      to the therapeutic effects, in TCM terms, of subduing the pathogenic wind and
      tranquilizing the mind.

PMID- 11977511
TI  - Experience in acupuncture treatment of dizziness and vertigo--a report of 3
      cases.

PMID- 11977512
TI  - Effects of electro-acupuncture on immune function after chemotherapy in 28 cases.
AB  - PURPOSE: To observe the effects of electroacupuncture therapy on T cells and
      activity of NK cell in the patient of Chemotherapy. METHOD: Electro-acupuncture
      therapy was simultaneously applied during chemotherapy, T cells and activity of
      NK cell of patients were determined before electroacupuncture treatment (before
      chemotherapy) and after 4-course electro-acupuncture treatments. RESULTS: Before
      chemotherapy, CD3 was low within the normal range, CD4 was much lower than the
      normal range, and CD8, CD4/CD8 and activity of NK cell were within the normal
      range. After one month of chemotherapy combined with electro-acupuncture, no
      decline of all the indices was found (P > 0.05). CONCLUSION: Electro-acupuncture
      can really increase the immune function of patients of chemotherapy.

PMID- 11977513
TI  - Treatment for injury of superior clunEal nerves by triple puncture needling with
      massage.

PMID- 11977514
TI  - Clinical application of blood-letting therapy.

PMID- 11977515
TI  - Acupuncture treatment for 34 cases of uremic cutaneous pruritus.

PMID- 11977516
TI  - Twenty-eight cases of diabetic foot ulcer and gangrene treated with the Chinese
      herbal medicine combined with injection of ahylsantinfarctase.

PMID- 11977517
TI  - Acupuncture treatment for 34 cases of epiphora with dysfunction of lacrimal duct.
AB  - We have treated 34 cases of epiphora due to dysfunction of the lacrimal duct with
      a warm needle puncturing at the Jingming (UB 1) point. The effect was
      significantly better than that of the control group treated with lacrimal duct
      irrigation and norflaxacin eye drops (a total effective rate of 91.07% vs.
      54.29%).

PMID- 11977518
TI  - Thirty-six cases of infantile proctoptosis treated by extremely shallow puncture.

PMID- 11977520
TI  - New exploration of needling manipulations at point Tianzong.

PMID- 11977519
TI  - Dr. Zhang's experience in massotherapy for treatment of vertebral-artery-type
      cervical spondylopathy.
AB  - Thirty cases of vertebral-artery-type cervical spondylopathy were treated by Dr.
      Zhang Tao's technique. The cure rate was 50%, and the total effective rate was
      100%.

PMID- 11977521
TI  - GAP-43 expression and pathological changes of temporal infarction in rats and
      effects of batroxobin.
AB  - To study the changes of the expression of growth-associated protein-43 (GAP-43)
      and pathology in temporal infarction of rats photochemically induced and the
      effects of batroxobin. METHODS: Immunohistochemical technique and hematoxylin
      eosin stain was used to show the changes of the expression of GAP-43 and
      pathology. RESULTS: In infarction group, GAP-43 expression was markedly increased
      on the infarction and surrounding tissues at 24 h cerebral infarction. The
      expression reached peak level at 72 h after cerebral infarction and was decreased
      at 7 d after cerebral infarction. However, in batroxobin-treated group, GAP-43
      expression was increased and the pathological changes were much slight as
      compared with infarction group. CONCLUSION: The expression of GAP-43 increases in
      infarction of temporal neocortex and batroxobin promotes the expression of GAP-43
      and ameliorates the pathological changes in infarction of temporal neocortex.

PMID- 11977522
TI  - The effects of electroacupuncture at the heart meridian on myocardial contractile
      function in rabbits with myocardial ischemia.
AB  - Acute myocardial ischemia was induced by intravenous injection of pituitrin, and
      electroacupuncture (EA) was applied at the Heart and Lung Meridians (HM and LM),
      3 points on each meridian. The changes in the left intraventricular pressure
      (LVP), the maximum rise rate of intraventricular pressure (LVP dp/dtmax), the
      area of cardiac force loop (ACFL), and the maximum shortening velocity of
      myocardial contractile element (Vmax) were observed. As a result, there were
      significant differences in the improvement of LVP, LVP dp/dtmax, ACFL and Vmax
      between EA at HM and LM. The regulatory action of EA at HM on the myocardial
      contractile function was significantly better than that of EA at LM, indicating
      that HM has a close relationship with the myocardial contractile function.

PMID- 11977523
TI  - Treatment of cough and dyspnea due to acute bronchitis by plaster for cough and
      dyspnea--a report of 735 cases.
AB  - In the light of the theory of treating the internal disease externally, an
      externally used plaster for treating cough and dyspnea due to acute bronchitis
      (Ke Chuan Yi Tie Kang [symbol: see text]-[symbol: see text]) was successfully
      applied to 735 cases of acute bronchitis (the treatment group), with the other
      423 cases treated with routine western drugs as controls. The results showed that
      the cure rate in the treatment group was significantly higher than that in the
      control group (P < 0.01); and that in the treatment group, the cure rate for the
      wind-cold type of acute bronchitis was significantly higher than that for the
      wind-heat type of acute bronchitis (P < 0.01).

PMID- 11977524
TI  - Effect of acupuncture on free radicals in rats with early experimental spinal
      cord injury.
AB  - Effect of acupuncture on free radicals after spinal cord injury was observed in
      rats with experimental spinal cord injury (SCI). Results indicated that within 24
      hours after SCI malondialdehyde (MDA) increased progressively, 2 hours after SCI
      it reached the peak; and the superoxide dismutase (SOD) activity decreased
      significantly at the same hours, the decrease being the most marked 2-6 hours
      after SCI. The MDA content in the acupuncture group was significantly lower (P <
      0.05) and the SOD activity higher (P < 0.01) than that of the control group
      respectively. It is suggested that acupuncture inhibits production of MDA and
      increases the SOD activity.

PMID- 11977525
TI  - Effects of different compounding of formulae on content of gardenoside in Yin
      Chen Hao decoction.
AB  - In order to observe the effects of the ground and intact Zhi Zi (Fructus
      Gardeniae) and different combinations of the ingredients and refined single
      Chinese drug granules in Yin Chen Hao Decoction compound prescription on the
      contents of gardenoside (an effective component of the prescription), the
      contents of gardenoside were determined with reversed phase high performance
      liquid chromatography (HPLC), with acetonitrile-water (15:85) as mobile phase, at
      wave length 238 nm. The results indicated that the gardenoside-decocted-out rates
      in the decoctions prepared by different combinations of the ingredients with the
      ground Zhi Zi (Fructus Gardeniae) all were higher significantly than those in the
      decoction with intact Zhi Zi (Fructus Gardeniae), and generally, different
      combinations of the ingredients in the decoction had only little effect on the
      gardenoside-decocted-out rate.

PMID- 11977526
TI  - Advances in experimental studies on treatment of psoriasis by traditional Chinese
      medicine.
AB  - Traditional Chinese medicine has demonstrated its strength in treating psoriasis,
      which is characterized by a variety of methods of treatment, flexible use of
      drugs, high efficacy, low recurrence, and few side-effects. Experimental studies
      on the mechanism governing the TCM treatment of psoriasis have been conducted at
      the cellular level and the molecular level. The studies on proliferation and
      differentiation of keratinocytes and the inhibitory effect against them,
      apoptosis, intercellular adhesion molecules, cytokine, and haemorheology indicate
      that the laboratory studies on the treatment of psoriasis have now entered a very
      high stage since the eighties. The studies on relationship between typing of
      psoriasis based on TCM differentiation of symptoms and signs and changes in some
      laboratory indexes have been carried out by some researchers to explore the
      inherent pathological changes in typing of psoriasis based on TCM differentiation
      of symptoms and signs and to provide scientific basis for the differentiation and
      typing under a unified standard. However, the present studies lack depth and
      scope in the methods. In future, the laboratory studies should be enhanced to go
      further into the principles governing the TCM treatment of psoriasis and to seek
      new drugs that will be even more effective for psoriasis and can bring its
      relapse under control.

PMID- 11977527
TI  - The present state and perspective in treatment of primary osteoporosis by
      acupuncture and moxibustion.

PMID- 11977528
TI  - How to differentiate and treat Bi-syndrome by acupuncture and moxibustion?

PMID- 11977529
TI  - Diarrhea.

PMID- 11977530
TI  - The effect of acupuncture on bone mineral density in postmenopausal women.

PMID- 11977531
TI  - [Monoclonal antibody for cancer treatment].
AB  - Antibodies have for many decades been viewed as ideal molecules for cancer
      therapy. Although promising from the start, it has taken much of more than two
      decades to reach the level of clinical application. Genetic engineering of
      antibodies; that is novel technologies for chimeric or humanizing monoclonal
      antibodies, has greatly advanced their utility in molecular targeting therapies,
      and in the past four years some therapeutic monoclonal antibodies for hematologic
      malignancies and solid tumors, such as Rituximab for B-cell lymphoma and
      Trastuzumab for metastatic breast cancer, have provided sufficient efficacy and
      safety to support regulatory approval from the U.S. Food and Drug Administration.
      They were subsequently approved by the Japanese Ministry of Health, Labour and
      Welfare in 2001. Many molecular biological and immunological studies have
      revealed the targeting properties of the host immune system and the biological
      mechanism of cancer cells for a more specific anticancer effect. Many clinical
      trials of monoclonal antibodies as a single agent, or in combination protocol
      with current standard chemotherapy or immunoconjugates have shown promise in the
      treatment of specific diseases. Furthermore, novel antibody designs and improved
      understanding of the mode of action of current antibodies lend great hope to the
      future of this therapeutic approach. The accumulating results from many basic,
      clinical and translational studies may lead to more individualized therapeutic
      strategies using these agent directed at specific genetic and immunologic
      targets.

PMID- 11977533
TI  - [Multiple endocrine neoplasia].
AB  - In multiple endocrine neoplasia (MEN) syndromes, tumors appear either
      synchronously or heterochronously in a combination of 2 or more specified
      endocrine glands. They are broadly classified as MEN 1 or MEN 2 according to the
      combination of tumors, and are inherited as an autosomal dominant trait. The
      genes responsible for these syndromes have been identified, making early
      diagnosis based on familial screening possible. The gene responsible for MEN 1 is
      located on the long arm of chromosome 11. It is a tumor suppressor gene that
      codes for menin. The cause of MEN 2 type is a mutation of the RET proto-oncogene
      on the long arm of chromosome 10. The present article discusses the diagnosis and
      treatment of these syndromes.

PMID- 11977532
TI  - [Genetic testing and counseling for familial tumor syndromes].
AB  - Recent developments in molecular biology have increased our understanding of the
      genetics of familial tumor syndromes. Isolation of the responsible genes has made
      it possible to identify gene carriers before they manifest clinical symptoms,
      which enables early detection of disease and at times prophylactic surgery.
      Indications for genetic testing of susceptible family members, however, should be
      carefully considered. Genetic counseling must be provided to clients before
      genetic tests. Patients should be provided with the latest knowledge on the
      disease and appropriately informed of the benefits and possible problems
      associated with genetic test, as such information is essential for clients to
      decide whether they will undergo such tests. Genetic medicine is not sufficiently
      available at present in Japan. Establishment of genetic services that deal with
      genetic counseling, family support and ethical, social and legal issues is
      strongly desired.

PMID- 11977534
TI  - [Genetic test and prophylactic treatment in breast cancer families].
AB  - Fifteen (13.3%) and 21 (18.6%) deleterious germline mutations were identified in
      BRCA1, and BRCA2 genes among 113 Japanese breast cancer families. We found a
      BRCA1 codon 63 (nucleotide 307) nonsense mutation and a 4-bp deletion at codon
      1858 (nucleotide 5802) of BRCA2 in 4 and 7 independent families, respectively.
      Haplotype analysis has revealed that these two mutations were founder mutations.
      Lifetime risk of breast cancer in BRCA1 or BRCA2 mutation carriers was estimated
      at nearly 80%, and that of ovarian cancer in BRCA1 mutation carriers was about
      40%. A questionnaire survey as to the genetic testing (BRCA1 and BRCA2) and
      prevention was carried out with 146 healthy women (hospital workers or medical
      students) and 84 breast cancer patients. About 80% of healthy women as well as
      breast cancer patients responded positively to the genetic testing, based on the
      assumption their's was a breast cancer family, and about 20% of each group
      answered that they would opt for prophylactic mastectomy and oophorectomy if they
      were found to be germline mutation carriers. These results indicate that genetic
      testing and prophylactic surgery would be acceptable among a considerable number
      of Japanese women, and seem to support the establishment an infrastructure for
      genetic testing in Japan.

PMID- 11977535
TI  - [Diagnosis and treatment for familial gastric cancer].
AB  - The criteria for familial gastric cancer are as follows: 1) there should be at
      least 3 relatives with gastric cancer, 2) one should be a first-degree relative
      of the other 2, 3) at least 2 successive generations should be affected, 4) at
      least 1 should be diagnosed before age 50, and 5) other familial tumors should be
      excluded. There are two types of familial gastric cancer, diffuse type and
      intestinal type, of which the genetic background seems to be differ. In 1998, an
      autosomal dominant syndrome of diffuse gastric cancer was reported with germline
      mutations in the E-cadherin gene and has been identified in approximately 14
      families and 50 individuals worldwide. In addition, an inherited mutation in
      mismatch repair (MMR) genes was found in hereditary non-polyposis colorectal
      cancer (HNPCC) in 1993. Since there is high frequency microsatellite instability
      found in familial gastric cancer patients, vigorous efforts have been made to
      find abnormalities in MMR genes of familial gastric cancer patients. However, to
      date, there has been little progress in detecting MMR gene mutations in familial
      gastric cancer patients. It is clinically most important to obtain a detailed
      family history to identify familial gastric cancer patients. At present,
      prophylactic total gastrectomy for familial gastric cancer is under careful
      consideration.

PMID- 11977536
TI  - [Familial adenomatous polyposis (FAP)--diagnosis and management].
AB  - Familial adenomatous polyposis (FAP) is characterized by more than hundreds of
      colorectal adenomas, colorectal cancer in early adult life, extracolonic features
      and genetic inheritance. Not only surgical management of FAP (IAA, IACA and IRA)
      but also methodology of APC gene test is almost established. Surveillance program
      and management of extracolonic manifestation is going to contribute to patient's
      prognosis. And now in Japan, two clinical intervention and chemoprevention trial
      studies of FAP are going on. As these reasons, FAP is most comprehensive model
      for understanding status quo and future problem of familial cancer syndromes.
      However, there are many counseling issues of FAP family members, choice of
      opportunity and method for diagnosis, surveillance, chemoprevention, surgery and
      to inform family member about hereditary risk. So, Cancer Genetic Counseling for
      FAP family members must be provided for their lifetime long.

PMID- 11977538
TI  - [Cancer prevention in familial cancer].
AB  - We established a protocol for and will conduct an interventional randomized
      controlled trial for the prevention of colorectal cancer. The subjects will be
      100 patients with hereditary non-polyposis colorectal cancer. Two regimens were
      formulated for the prevention of colorectal cancer. Regimen A is dietary guidance
      and ingestion of aged garlic extract (AGE) capsules, and regimen B is dietary
      guidance and non-function capsules. The main end point of the trial is number and
      size of colorectal adenomas after 2 years. Subject recruiting was started in
      March, 2002. The trial will be completed in September, 2005.

PMID- 11977537
TI  - [Hereditary non-polyposis colorectal cancer (HNPCC)].
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is a type of hereditary
      colorectal cancer with autosomal dominant traits. Its causal genes are mismatch
      repair genes such as the hMSH2 and hMLH1 genes. Owing to its frequency, juvenile
      onset, and the outbreaks of multiple colorectal cancers and cancers occurring
      over multiple organs, it is recognized as a very important disease for the
      purpose of understanding not only colorectal cancers, but also other digestive
      cancers, and furthering pathological inquiry into the state of cancers in
      general.

PMID- 11977539
TI  - [CGS 20267 (Letrozole), a new aromatase inhibitor: early phase II study for
      postmenopausal women with advanced breast cancer].
AB  - A multicenter, open labeled, randomized early Phase II study for CGS 20267 was
      conducted at the doses 0.5 mg once daily and 1.0 mg once daily in postmenopausal
      women with advanced breast cancer. Sixty-four patients were randomly assigned to
      the doses of either 0.5 mg once daily (n = 33) or 1.0 mg once daily (n = 31).
      Thirty-one patients were eligible for 0.5 mg group, and 29 for 1.0 mg group. A
      total of 57 patients (30 in the 0.5 mg group and 27 in the 1.0 mg group) were
      eligible for the evaluation of efficacy. There were 3 CR, 5 PR, 5 stable disease
      (SD: NC lasting over 24 weeks), 7 NC and 10 PD in the 0.5 mg group. The objective
      response rate (ORR) was 26.7%. There were 4 CR, 7 PR, 8 SD, 3 NC and 5 PD in the
      1.0 mg group. The ORR was 40.7%. A total of 57 patients (29 in the 0.5 mg group
      and 28 in the 1.0 mg group) were eligible for safety evaluation. Adverse clinical
      events related to CGS 20267 in the 0.5 mg group were headache, nausea, cold
      sweat, sleepiness and muscle ache in the lower extremities (2 patients, incidence
      rate 6.9%) whereas those in the 1.0 mg group were generalized itching and
      generalized hot feeling (2 patients, incidence rate 7.1%). All of the adverse
      events were grade 1 except the generalized itching which was grade 2. CGS 20267
      related abnormalities in the laboratory tests for the 0.5 mg group were a
      decrease in WBC, and increases in GOT, GPT, LDH and gamma-GTP (5 patients, 14.3%)
      whereas those in the 1.0 mg group were increases in GPT, gamma-GTP, alkaline
      phosphatase, and total bilirubin (1 patient, 3.6%). The increases in GOT and GPT
      were grade 2, but others were grade 1. The data show both CGS 20267 0.5 mg once
      daily and 1.0 mg once daily to be effective and tolerable in the treatment of
      postmenopausal women with advanced breast cancer.

PMID- 11977540
TI  - [The preventive effect of allopurinol spray on stomatitis induced by anti-cancer
      drugs].
AB  - The present study was conducted to evaluate the effect of allopurinol spray on
      stomatitis induced by chemotherapy for esophageal cancer. The chemotherapeutics
      used consisted of 5-FU + CDDP (FC) given to 40 patients and 5-FU + ND (FN) given
      to 9 patients. Allopurinol solution for spray was prepared using a gelatin agent
      as base. The allopurinol spray was used 3-5 times daily before and after
      chemotherapy. The Japan Society for Cancer Therapy's criteria for stomatitis were
      used. With FN-therapy, no stomatitis was observed. With FC-therapy, 9 of 40
      patients developed stomatitis of grade 1 (8 patients) or grade 2 (1). The
      incidence of stomatitis was 18.4% with all therapies and 22.5% with FC-therapy.
      The average graded toxicity was 0.20 for all therapies and 0.25 for FC-therapy.
      These results suggest that allopurinol spray is markedly effective for the
      prevention of stomatitis induced by chemotherapy. In addition, allopurinol spray
      is portable and convenient, and resulted in less nausea or vomiting than
      mouthwash.

PMID- 11977541
TI  - [The effect of L-Glutamine and Shakuyaku-Kanzo-to for paclitaxel-induced
      myalgia/arthralgia].
AB  - Myalgia/arthralgia is a crucial side effect of paclitaxel, and may become the
      major dose-limiting side effect. However, this is a situation where there is
      little effective preventive treatment. L-Glutamine was reported as a
      neuroprotective agent for vincristine-induced neurotoxicity. In Japan, there have
      been reports on steroid and Shakuyaku-Kanzou-to (a herbal medicine) for
      paclitaxel-induced myalgia/arthralgia. This study aimed to compare the effect of
      L-Glutamine and Shakuyaku-Kanzou-to, and to discuss the validity of these agents
      for the paclitaxel-induced myalgia/arthralgia. Our results suggested that
      Shakuyaku-Kanzou-to showed no remarkable effects against paclitaxel-induced
      myalgia/arthralgia as had been reported before; however, both L-Glutamine and
      Shakuyaku-Kanzou-to decreased the duration of grade 2 toxicity (CALGB Expanded
      Common Toxicity Criteria) in comparison with those who were not treated. L
      Glutamine and Shakuyaku-Kanzou-to might therefore a preventive effect against
      moderate or severer myalgia/arthralgia during paclitaxel-treated chemotherapy.
      Further trials are needed to confirm the value of these drugs.

PMID- 11977542
TI  - [Antitumor activity of combination treatment combining gemcitabine with topotecin
      against human lung cancer xenografted in nude mice].
AB  - Gemcitabine is a new deoxycytidine derivative that shows a distinguishing, potent
      antitumor activity against various human tumor lines transplanted to nude mice.
      We have investigated the antitumor activity of gemcitabine combined with
      cisplatin (CDDP) or vindesine (VDS) using a lung cancer line, H-74, that was
      insensitive to almost all antitumor drugs and relatively insensitive to
      gemcitabine. We found that the antitumor effects of gemcitabine combined with
      CDDP or VDS were more potent and lasted longer than that of each drug alone,
      without an increase in side effects such as body weight loss. In this study, the
      antitumor activity of combined gemcitabine with topotecin (CPT-11) was evaluated
      using a similar method for 8 weeks, including a 4-week treatment period and a
      subsequent 4-week drug-free period, with reference to tumor growth inhibition
      rate, histological changes, and side effects. The treatment combining gemcitabine
      with CPT-11 administered at each 1/2 MTD showed an additive effect at 4 and 8
      weeks after start of administration. Furthermore, no remarkable side effects were
      observed. Since these study results demonstrated that gemcitabine combined with
      CPT-11 increased and prolonged the antitumor activity without increasing side
      effects such as body weight loss, it is expected that CPT-11 could be one of the
      useful drugs used in combination with gemcitabine for lung cancer therapy.

PMID- 11977544
TI  - [Sustained complete response in lung metastasis of breast cancer by goserelin-
      report of two cases].
AB  - We report two patients with lung metastasis of breast cancer who had durable
      complete responses (CR) with goserelin. The first patient was a 48-year-old woman
      diagnosed with left breast cancer (T1N0M0, Stage I) at the age of 40, for which
      she underwent mastectomy. The tumor was estrogen receptor (ER) and progesterone
      receptor (PgR) positive. She received tamoxifen for 2 years as adjuvant therapy.
      After 8 years and 7 months, a lung metastasis was found by chest X-p, and
      treatment with goserelin was started. After 11 months of this treatment a CR was
      achieved, and the response lasted 3 years and 5 months. The second patient was a
      38-year-old woman with a diagnosis of lung metastasis. She underwent right
      mastectomy at the age of 29 for breast cancer (T2N1M0, Stage IIB), and the tumor
      was ER and PgR positive. She received tamoxifen and doxifluridine for 2 years as
      adjuvant therapy. Eight years and 6 months after the mastectomy, a lung
      metastasis was found by chest X-p, and goserelin treatment was started. After 8
      months of this treatment, chest X-p and CT revealed a complete regression of the
      lung metastasis, and response lasted 1 years and 7 months. Serum estradiol levels
      were suppressed below 10 pg/ml during the treatment in both patients. These
      results indicate the usefulness of LH-RH agonist in the treatment of recurrent
      breast cancer.

PMID- 11977543
TI  - [A case of effective paclitaxel therapy for adriamycin resistant metastatic
      breast cancer with brain metastases].
AB  - A 36-year-old woman was referred to our hospital because of a right breast lump.
      Chest computed tomography revealed pulmonary metastases with lymphangitis
      carcinomatosa. Additional examination revealed liver metastases and axillary and
      cervical lymph node metastases. The patient was started on CA therapy
      (cyclophosphamide 900 mg, adriamycin 90 mg). A minor response was observed in the
      pulmonary metastases after two courses but new brain metastases were detected. We
      then tried paclitaxel administration (260 mg). A partial response was observed in
      the brain and pulmonary metastases. Thus, paclitaxel administration was continued
      on a weekly basis (120 mg) and the brain and pulmonary metastases continued to
      diminish. The primary breast cancer, liver metastases and axillary and cervical
      lymph node metastases were disappeared. Whole brain radiation was done with
      weekly paclitaxel administration and the brain metastases were diminished even
      more. Paclitaxel is as a radiosensitizer and seems to have a strong
      antineoplastic effect with concurrent radiation.

PMID- 11977545
TI  - [A case of gastric cancer in the stomach wall used for mediastinal reconstruction
      after esophagectomy in which surgery was abandoned due to advanced age and
      complications but TS-1 was useful].
AB  - The patient was a 78-year-old man. Gastric cancer, type 3, was diagnosed by
      endoscopy in the subtotal stomach used for posterior mediastinal reconstruction
      after resection of thoracic esophageal cancer. Surgery was not considered to be
      feasible in this case because of cerebral infarction and decreased pulmonary
      functions; instead, the patient received TS-1 chemotherapy. Drug administration
      was started at the dose of 100 mg/day, one level lower than the standard dose of
      TS-1. Reduction in tumor size was noted endoscopically during the first course of
      treatment. At the end of the 4th course of treatment, the ulcerous lesion was
      found to have disappeared almost completely, and only mild mural irregularity was
      noted. The incidence of gastric cancer in the stomach tissue used for mediastinal
      reconstruction after esophagectomy has been reported to be 0.8%. In many of these
      cases, the cancer is already advanced at the time of diagnosis, precluding
      surgical resection. In this situation, chemotherapy with TS-1 is expected to be
      an effective method of treatment that can be administered at home in elderly
      patients with a variety of complications.

PMID- 11977546
TI  - [A case of hepatocellular carcinoma with portal tumor thrombus effectively
      treated by arterial infusion chemotherapy with low-dose cisplatin and 5
      fluorouracil].
AB  - A 69-year-old female with unresectable hepatocellular carcinoma was treated with
      continuous arterial infusion of low-dose cisplatin (10 mg/body/day) and 5
      fluorouracil (250 mg/body/day). The regimen was continued for 5 days then
      discontinued for 2 days, and repeated for 4 weeks. The portal tumor thrombus
      almost disappeared and HCC was smaller than before chemotherapy. Tumor marker
      (AFP and PIVKA-II) decreased remarkably. As tumor markers increased again 2
      months later, the same regimen chemotherapy was performed once more. The patient
      was treated with arterial chemotherapy as an outpatient. The present case of
      hepatocellular carcinoma with portal tumor thrombus was effectively treated by
      arterial infusion chemotherapy with low dose cisplatin and 5-fluorouracil.

PMID- 11977547
TI  - [A case of gastric cancer with paraaortic lymph node metastasis responding to
      preoperative chemotherapy and surviving 4 years and 4 months after total
      gastrectomy].
AB  - A 68-year-old woman was admitted to our hospital because of type 4 gastric cancer
      associated with paraaortic lymph node metastasis. Considered surgically
      incurable, she was placed on preoperative chemotherapy consisting of Methotrexate
      (MTX) 50 mg (day 1), CDDP 10 mg (day 2-6), 5-FU 500 mg (day 1-6) and Leucovorin
      (LV) 60 mg (day 2-6). Because of severe nausea and leucopenia, she could receive
      only 1 course of the chemotherapy. CT on January 7, 1997 (5 weeks after the
      chemotherapy) showed that the gastric wall thickness and the paraaortic lymph
      nodes swelling had decreased remarkably. She underwent total gastrectomy on
      January 13, 1997 (pT2, pN2, pM1 (LYM), stage IV, TNM classification). As an
      outpatient, she was treated with UFT-E 300 mg/day (continuous until the present)
      and MTX 50 mg (day 1), 5-FU 500 mg (day 1) and LV 60 mg (day 2-3) once two weeks
      (total 27 cycles). Four years and 4 months after surgery, although peritoneal
      recurrence was suspected, she has been managed at our outpatient clinic.

PMID- 11977549
TI  - [A case of advanced gastric carcinoma with liver metastasis with no recurrence
      and long survival by means of surgery and postoperative chemotherapy].
AB  - A 69-year-old man was diagnosed with type 2 advanced gastric carcinoma at the
      antrum of the stomach with liver metastasis (S8) in July 1995. Operative staging
      was H1P0T2N2 stage IV. Distal partial gastrectomy was performed with combined D2
      lymphadenectomy and partial hepatectomy. Fifty-six courses of low-dose
      chemotherapy with CDDP and 5-FU were administered from the time of surgery to
      March 1997. Sequentially the administration of UFT (150 mg/day, orally) was
      continued up to the present. The patient still has had no recurrence 6 years and
      3 months after operation. Aggressive treatment combining surgery and long-term
      postoperative chemotherapy is potentially useful in contributing to long survival
      in cases of advanced gastric cancer with liver metastasis.

PMID- 11977548
TI  - [A patient with metastatic gastrointestinal stromal tumor who responded to
      STI571].
AB  - We report a case of gastrointestinal stromal tumor (GIST) with multiple hepatic
      metastases that responded to tyrosine kinase inhibitor STI571. A 30-year-old
      woman underwent total gastrectomy on July 10, 1998, with a diagnosis of
      submucosal tumor of the stomach. Pathological analysis of the primary lesion
      revealed strong expression of c-kit, and it was diagnosed as GIST. The patient
      underwent tumor excision due to peritoneal recurrence on May 1, 2000 and November
      13, 2000. On August 8, 2001, multiple liver metastases were detected by abdominal
      CAT scan. Treatment with STI571 at a dose of 400 mg/day for 28 days was initiated
      on September 14, 2000. CAT scan showed rapid tumor shrinkage after 3 weeks of
      treatment (reduction rate of 56%) and the response continued after 7 weeks of
      treatment (reduction rate of 71%). Thus, we evaluated the response as PR.
      Leukocytopenia, edema, diarrhea and nausea were observed; however, all toxicities
      were mild and tolerable. This case suggests the efficacy of STI571 for metastatic
      GIST.

PMID- 11977551
TI  - [A case report of effective chemoradiation with 5'-DFUR and concomitant
      preoperative radiotherapy of the lower rectum].
AB  - We treated a lower rectal carcinoma patient with preoperative radiation and
      chemotherapy, resulting in a downstaging, and the findings are reported herein.
      The patient is a 55-year-old woman endoscopically diagnosed with advanced rectal
      carcinoma at a site 3 cm from the dental line. Preoperative radiation and
      chemotherapy included whole pelvis irradiation (44 Gy in total) and 800 mg/day of
      5'-DFUR administered until one day before the operation. On the 20th day after
      completing irradiation, a low anterior resection of the rectum was conducted.
      During the operation, we found serositis of the small intestine and
      retroperitoneal fibrosis thought to be due to the irradiation. Histopathologic
      findings showed: invasion degree, sm2; stage I with N0; and histologic grading,
      Grade 2. The patient started drinking water from postoperative day 1, and was
      discharged on postoperative day 11. At present, in Europe and the USA, large
      scale studies are being conducted to evaluate preoperative radiation and
      chemotherapy in patients with lower rectal carcinoma. We think that this therapy
      is an effective treatment, since a distance (AW) from the lower margin of the
      tumor and the cut edge of the anal end can be established.

PMID- 11977553
TI  - [A case of recurrent rectal cancer responding to weekly low-dose CPT
      11/isovorin/5-fluorouracil].
AB  - We report the case of 66-year-old male with recurrent rectal cancer which
      responded to chemotherapy using CPT-11, Isovorin, and 5-fluorouracil (5-FU). CPT
      11 was administered at 40 mg (90 min i.v.) x 3 day/week, and Isovorin and 5-FU
      were administered at 25 mg (bolus) and 250 mg (continuous) x 5 day/week by
      intraarterial infusion. Three cycles of this weekly regimen resulted in
      regression of tumors in the iliac region with remission of the lameness caused by
      iliac pain. The serum CEA level decreased from 13.1 ng/ml to 0.5 ng/ml. The
      patient has undergone 13 cycles of the regimen modified for outpatients (CPT-11
      at 40 mg x 3 day/week plus Isovorin at 25 mg and 5-FU at 250 mg 1 day/week) with
      inhibitions of tumor regrowth and improved serum CEA level for more than 12
      months. The current case suggests that weekly low-dose CPT-11/Isovorin/5-FU may
      have a potent therapeutic effect against recurrent rectal cancer.

PMID- 11977550
TI  - [A case of complete response (CR) persisting for 2 years and 10 months from UFT-E
      in a patient with liver metastasis of gastric cancer].
AB  - A 63-year-old man was admitted to our hospital because of advanced gastric cancer
      associated with metastasis of the liver. He was treated with 300 mg/day of UFT-E
      from 18 days after total gastrectomy on July 14, 1997. The preoperative serum
      level of tumor marker, which had been increasing (CEA: 340 ng/ml, CA19-9: 9,094
      U/ml), returned to the normal range 7 months after gastrectomy. CT scan on July
      9, 1998 (1 year after gastrectomy) showed that the liver metastasis had changed
      to a scar (CR). As of May, 2001, 2 years and 10 months after inducing CR, we have
      been administering UFT-E to the patient, with no side effect or regrowth of the
      tumor.

PMID- 11977552
TI  - [A case of liver metastasis of rectal cancer demonstrating complete response to 5
      FU + Leucovorin + UFT].
AB  - Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme that metabolizes
      5-fluorouracil (5-FU). We report a patient with metachronous liver metastasis
      from rectal cancer with low expression of DPD, who demonstrated complete response
      to chemotherapy comprising 5-FU, Leucovorin, and UFT. A 53-year-old man underwent
      macroscopically curative proctectomy with coloanal anastomosis for lower rectal
      cancer (Curability B). The DPD level in the primary tumor determined by an enzyme
      linked immunosorbent assay was extremely low (10.3 U/mg.protein). Three months
      postoperatively, 5-FU (333 mg/m2) + Leucovorin (200 mg/m2) therapy (once a week
      for 3 weeks with a one-week rest interval, repeatedly) was started as an adjuvant
      therapy. However, computed tomography demonstrated a solitary liver metastasis 3
      cm in size 1 month later. Chemotherapy was continued with dose escalation of 5-FU
      (500 mg/m2) and with oral administration of UFT-E (400 mg/body, daily). Five
      months later, computed tomography did not detect the liver metastasis, and this
      finding was maintained for two months (complete response). This case provides
      evidence that a low expression of DPD in the primary lesion is related to a
      favorable response of liver metastasis to 5-FU-based systemic chemotherapy.

PMID- 11977554
TI  - [The incidence of phlebitis in the patients administrated vinorelbine by
      intravenous bolus injection--a retrospective study].

PMID- 11977555
TI  - [Tumor markers in gastric cancer].
AB  - There are two markers, pepsinogen isoenzymes and antibody against Helicobactor
      pyroli, for screening of high-risk group for gastric cancer. Most of markers are
      used in diagnosis, staging, monitoring and differentiating subgroups of gastric
      cancer. Markers in ascitic fluid are used for diagnosing peritoneal invasion of
      gastric cancer.

PMID- 11977557
TI  - Background screening and safe hiring: an introduction.

PMID- 11977556
TI  - [Trastuzumab (Herceptin)].
AB  - The HER 2/neu protein is thought to be a unique and useful molecular target for
      antibody therapy of cancers overexpressing the HER 2/neu gene. The recombinant
      humanized anti-HER 2 monoclonal antibody trastuzumab (Herceptin) has been
      available for clinical use in metastatic breast cancer in Japan since June 2001.
      Some breast cancer patients have responded to trastuzumab alone. A phase III
      study showed significant efficacy of combination use with paclitaxel compared
      with paclitaxel alone. Trastuzumab has some toxicities including infusion
      reaction and cardiotoxicity. It is very rare that infusion reaction manifests
      lethally. Although trastuzumab should not be concurrently used with an
      anthracycline, cardiotoxicity was also identified in patients treated with
      trastuzumab alone. The cumulative dose of anthracycline has not yet been
      identified as a risk factor, but patients who have received a high cumulative
      dose should be treated with special caution. In this article, the details of this
      novel biologic agent are reviewed from basic and clinical studies.

PMID- 11977558
TI  - OSHA's eTool for Lockout/Tagout.

PMID- 11977559
TI  - Changing media in workplace programs.

PMID- 11977560
TI  - New solutions for ensuring a drug-free workplace.

PMID- 11977561
TI  - Stress and shiftwork.

PMID- 11977562
TI  - Present and unaccounted for.

PMID- 11977563
TI  - Pricked by a needle.

PMID- 11977564
TI  - Proper precautions.

PMID- 11977565
TI  - Adding AEDs to your safety program.

PMID- 11977566
TI  - Why an alternative keyboard? Think productivity!

PMID- 11977567
TI  - Critical elements for effective ergonomics, Part II.

PMID- 11977568
TI  - Discovering operational discipline.

PMID- 11977569
TI  - Fit to be tried.

PMID- 11977570
TI  - Using your brain to become ergonomic-minded.

PMID- 11977571
TI  - Tighter reins on who is 'disabled'.

PMID- 11977572
TI  - [Quality in internal medicine].

PMID- 11977573
TI  - [Diagnosis and therapy of vascular diseases].

PMID- 11977574
TI  - [Prevention of thromboembolism with low molecular weight heparin (Dalteparin-Na)
      in risk pregnancy].
AB  - BACKGROUND: Venous thrombotic events still remain the leading cause of maternal
      morbidity and mortality. During pregnancy as well as post partum, hemostasis
      changes also in normal pregnant women. Coagulation is activated and fibrinolysis
      suppressed, the concentration of particular coagulation factors is increased,
      while inhibitor potential is decreased. Additionally, the venous blood stream is
      mechanically hampered by the gravid uterus. As a result of these physiologic
      changes, the risk of thromboembolism is elevated. The risk increases frequently
      in women with previous thromboembolic episodes, a family history of
      thromboembolism, hereditary or acquired thrombotic disorders as well as the
      appearance of additional exposure prothrombogenic factors such as immobilization,
      inflammation, and operation. Simultaneous presence of combined prothrombogenic
      factors conducts a potentiation of the risk of thromboembolism. To avoid
      thromboembolism or rethromboembolism during pregnancy or puerperium, an
      individual risk-adapted heparin prophylaxis is indicated. PATIENTS AND METHODS:
      17 pregnant women with inherited and/or acquired prothrombogenic disorders,
      eleven of them with previous thromboembolism episodes, were treated with low
      molecular weight heparin (LMWH; dalteparin-Na). The daily dose of 5,000-10,000 IU
      LMWH was applied subcutaneously by self-injection during pregnancy and up to 8
      weeks post partum. Every 4 weeks clinical and laboratory monitoring was
      performed. Basic parameters as well as the special coagulation marker TAT
      (thrombin-antithrombin complex) and D-dimer were analyzed. RESULTS: Under the
      therapy with LMWH (dalteparin-Na), no thromboembolic events during pregnancy or
      post partum could be observed. No serious bleeding complications, except small
      subcutaneous local hematomas, occurred. Bolus applications of LMWH by self
      injection were easy to practice, gained a good acceptance and high compliance.
      Increased TAT values above normal at the actual state of pregnancy could be
      suppressed to normal values by raising the LMWH dose. CONCLUSION: The individual
      thromboembolic prophylaxis with LMWH represents an effective and safe therapy in
      risk pregnancy with previous thromboembolic events and/or thrombotic disorders.
      TAT seems to be an effective marker for monitoring of the coagulation activity
      during pregnancy and puerperium. Under this management, thromboembolic
      prophylaxis can be optimized.

PMID- 11977575
TI  - [Endovascular aneurysm therapy--long-term treatment outcomes after 7 years].
AB  - BACKGROUND: Stentgrafts for endovascular treatment of abdominal aortic aneurysms
      (AAA) have been commercially available since 1994, with now large numbers of
      implantations all over the world. PATIENTS AND METHODS: From 1994-2001, 115
      patients were treated with Stentor, Vanguard and Talent stentgrafts in our
      institution. RESULTS: Late complications of the first- and second-generation
      stentgrafts as radiologic or surgical interventions to maintain complete
      exclusion of the aneurysm amounted to 30% with an additional 22% for observed
      endoleaks and configuration changes of the stentgraft. Third-generation
      stentgrafts had a lower complication rate of 12.2% for interventions and 18.3%
      for late endoleaks and graft changes. CONCLUSION: High costs of the devices, a
      pretty high late complication rate, and the uncertain maintenance of stentgraft
      function to prevent aneurysm rupture currently limit the widespread application
      of this new technology, leaving conventional aneurysmectomy the standard for
      aneurysm treatment and reserving the endovascular method for selected patients.

PMID- 11977576
TI  - [Possibilities and prospects of noninvasive bypass diagnosis. Comparison of
      different nuclear magnetic resonance tomography methods with conventional
      coronary angiography].
AB  - OBJECTIVE: The aim of the study was to evaluate the patency of coronary artery
      bypass grafts (CABGs) with different MR imaging techniques. PATIENTS: 25 patients
      with 63 bypass grafts and a total of 78 distal anastomoses were studied at a 1.5
      Tesla scanner. A 2-D T2-weighted breath-hold turbo spin echo sequence (Haste), a
      3-D breath-hold contrast-enhanced MR angiography sequence (Fisp-3-D), and 3-D
      angiography sequence in navigator techniques were used. RESULTS: With the Haste
      and Fisp-3-D sequences, 44 of the 47 patent and 14 of the 16 occluded grafts were
      recognized, the sensitivity and specificity were 94% and 88%, respectively. With
      the Haste sequence, 80% (43/54) of the distal anastomoses were seen in good image
      quality, and with the Fish-3-D sequence 70% (38/54). The navigator sequence
      showed less sensitivity and specificity (74% and 63%, respectively). CONCLUSION:
      The patency of CABGs can be evaluated noninvasively with the Haste and the Fisp-3
      D angiography sequences. Better results can be expected with the development of a
      blood-pool contrast medium and an improvement of the spatial resolution.

PMID- 11977577
TI  - [The ultrasound contrast medium levovist increases the thrombolytic effect of low
      frequency ultrasound].
AB  - BACKGROUND: Therapeutic application of ultrasound is a promising tool to develop
      an alternative or additional treatment modality of acute vessel occlusion. It has
      previously been shown that ultrasound enhances the effect of pharmacologic
      thrombolytic agents and has a thrombolytic potential in "stand-alone" therapy.
      The purpose of this study was to determine, whether the presence of the echo
      contrast agent Levovist further increases the thrombolytic efficacy of
      ultrasound. MATERIAL AND METHODS: Thrombolytic efficacy of low-frequency (20.5
      kHz) continuous-wave ultrasound was evaluated. Fresh human blood clots (age 3-6
      h) were sonicated for 10 min at an intensity of 0.35 W/cm2. The thrombolytic
      effect of ultrasound alone and in combination with rt-PA (3 micrograms/ml) was
      assessed with and without addition of Levovist (2 mg/ml). Loss in weight of each
      blood clot was used to measure the extent of thrombolysis. The number of thrombi
      in each group was between ten and 18. Experiments were carried out in sodium
      phosphate buffer, at a temperature of 37 degrees C, in a flow system with a flow
      rate of 15 ml/min. RESULTS: The use of ultrasound alone showed a significant
      thrombolytic effect (41.8% weight loss), as compared to a control group (24.2%).
      The addition of Levovist further increased thrombolysis to 44.7%, which was not
      significant. However, in combination with rt-PA, ultrasound-mediated thrombolysis
      could be significantly increased from 65.8% to 74.2%, when Levovist was added (p
      < 0.05). CONCLUSION: These data show that the thrombolytic efficacy of low
      frequency continuous-wave ultrasound in combination with rt-PA is augmented in
      the presence of Levovist.

PMID- 11977578
TI  - [Manifestations of atherosclerosis in various vascular regions. Similarities and
      differences regarding epidemiology, etiology and prognosis].
AB  - Pathologic studies have demonstrated that atherosclerosis involves the whole
      arterial vessel tree. In the Framingham study, cardiovascular risk factors could
      be defined with different prognostic value for the development of atherosclerosis
      in various vascular regions. The prognosis of patients with atherosclerosis in
      coronary, carotid or leg arteries is worse compared to a normal population.
      Moreover, patients with symptomatic lesions in one vascular bed often have
      additional asymptomatic atherosclerotic lesions in other vascular regions.
      Patients with atherosclerosis in multiple vascular regions have a worse prognosis
      than patients with atherosclerosis in one vascular bed only. In a study of 804
      patients, we could show a significantly higher incidence of cardiovascular events
      (death, myocardial infarction, stroke) in patients with coronary artery disease
      (CAD) and additional lesions in peripheral arteries (leg, carotid) during a 3.2
      year follow-up compared to those with CAD only. Local and systemic inflammatory
      processes in the arterial vessel wall are considered to play an important role
      with regard to plaque instability. It has been suggested, that besides the
      symptomatic atherosclerotic lesion, multiple stable or unstable lesions are
      present in the whole arterial vessel tree predicting the patient's prognosis.
      Chronic infections with multiple pathogens ("concept of infectious burden")
      probably play an important role by triggering these inflammatory processes.
      Therefore, systemic therapeutic regimes are necessary for the treatment of
      patients with atherosclerosis. The platelet aggregation inhibitors improve the
      prognosis of patients with atherosclerosis in all vascular areas. Another
      important therapeutic regime is the use of statins, which seem to be not only
      effective in lipid lowering but also in plaque stabilization.

PMID- 11977579
TI  - [Atherosclerosis--progression by nonspecific activation of the immune system].
AB  - Atherogenesis is a disease of middle-sized and large-caliber blood vessels that
      can be divided into three major phases. The initial lesions of early
      atherosclerosis are characterized by the adhesion and subendothelial emigration
      of blood-borne monocytes, which differentiate into macrophages and provide the
      morphologic basis for the formation of foam cells and fatty streak lesions. These
      lesions are found in most children and teenagers in industrialized nations. The
      next key event in atherogenesis is the proliferation of smooth muscle cells
      within the intima and media, resulting in the gradual compromise of the vessel
      lumen. Myofibroblastic cells also contribute to lesion growth through the
      production of excessive amounts of extracellular matrix. Such lesions are
      clinically silent unless progression to the next phase continues: the lesions
      degenerate, forming a mostly necrotic "lipid core" consisting of extracellular
      lipid, cholesterol crystals, inflammatory cells and necrotic debris. A fibrous
      cap is formed which prevents the interaction of blood cells, particularly of
      platelets with the highly proaggregatory material found in the lipid core.
      However, continuous inflammatory activity and/or heightened mechanical stress
      (i.e., in hypertension) tends to weaken the fibrous caps. Eventually, plaque
      rupture ensues, platelets aggregate, and the lesions become clinically manifest
      in such dramatic events as myocardial infarction, stroke, or mesenteric ischemia.
      Research into lesion formation and progression is limited by the fact that
      lesions develop in silence over many decades and that animal models only
      incompletely model the situation in humans. Most currently debated concepts
      accept the "response to injury" hypothesis formulated by the late Russell Ross
      and the multi-factorial nature of atherogenesis. The discussion today circles
      around the relative contributions of low density lipoproteins (oxidized or
      enzymatically modified LDL?), the immune response (adaptive or innate?),
      infectious agents (CMV, Chlamydia pneumoniae?), and/or hereditary factors, to
      name only a few of the most widely debated concepts. Irrespective of the outcome
      of this pathomechanistic discussion, the knowledge of established risk factors
      (hypercholesterolemia, hypertension, diabetes, smoking, etc.) and protective
      interventions (lifestyle changes, physical exercise, "healthy" diets, effective
      dietary and pharmacologic control of hyperglycemia, blood pressure or
      hyperlipidemia) has helped to define atherosclerosis as a "new entity" that has
      little to do with the archaic concept of a "degenerative" vessel disease. The new
      concept takes us into the responsibility--puts us in charge of our own and our
      patients' cardiovascular risk--whether we like it or not. The smoking obese
      doctor no longer fits into the modern medical landscape.

PMID- 11977580
TI  - [Modern therapy in acute coronary syndrome].
AB  - Inhibition of platelet aggregation with aspirin and anticoagulation with
      unfractionated heparin can be considered the gold standard treatment of patients
      with acute coronary syndromes. Replacement of unfractionated heparins by low
      molecular weight heparins seem to further improve the cardiovascular risk.
      Additional treatment with glycoprotein IIb/IIIa receptor blockers led to a
      further reduction of the clinical event rate, especially in patients undergoing
      coronary interventions during an acute coronary syndrome (more than 30% relative
      risk reduction). However, the latter substances did only lead to marginal
      improvements in the setting of a conservative stabilization of patients with
      acute coronary syndrome (7% relative risk reduction). On the contrary, the
      initial treatment with clopidogrel in addition to aspirin and anticoagulation led
      to a 20% relative risk reduction for an endpoint of death, myocardial infarction
      and stroke in the CURE trial. The treatment with aspirin, clopidogrel (including
      loading-dose) for a treatment period of 3-12 months and anticoagulation for 2
      days can be considered the new standard of treatment in patients with acute
      coronary syndromes (unstable angina, non-ST-segment elevation, myocardial
      infarction). Glycoprotein IIb/IIIa receptor blockers should be used especially
      during coronary interventions. Antianginal treatment should include nitrates and
      betablockers. A treatment with statins and ACE-inhibitors should be initiated in
      the early course of acute coronary syndrome for plaque stabilization.

PMID- 11977581
TI  - [Interdisciplinary diagnosis and therapy of ischemic-osteomyelitic diabetic foot
      syndrome].
AB  - Advanced stages of the diabetic foot syndrome complicated by ischemia and
      osteomyelitis frequently result in minor amputation, followed by impaired wound
      healing and higher-level amputation in the context of regular health structures.
      Even in specialized foot care centers, peripheral arterial occlusive disease and
      osteomyelitis still represent the greatest challenge in the strife for limb
      salvage. Whereas the treatment of nonischemic foot lesions has increasingly
      become a matter of conservative medicine within recent years, for advanced
      diabetic foot wounds a multidisciplinary treatment policy is essential. A well
      coordinated treatment concept aiming at the elimination of the most relevant
      prognostic factors ischemia and osteomyelitis is required to achieve high limb
      salvage rates. Surgical revascularization by distal bypass is a crucially
      important element of this approach. Percutaneous transluminal angioplasty
      represents a complementary option for short-segment arterial occlusive disease.
      Foot-sparing minor surgery improves healing time and rates. A specialized
      diabetologic foot care clinic provides preclinical diagnosis, planning of
      inpatient procedures, and selection of patients requiring hospitalization for
      surgical intervention. In addition, it safeguards postinterventional care for
      wounds with secondary healing and measures of secondary prevention.

PMID- 11977582
TI  - [Pedal bypass surgery in diabetic foot syndrome: indications, technique and
      outcome].
AB  - Peripheral arterial occlusive disease in the diabetic patients is characterized
      predominantly by long segmental occlusion of the tibial arteries with patent
      segments of pedal arteries. Neuropathy and high susceptibility for foot infection
      explain the dramatically increased risk of major amputation. The pattern of
      arteriosclerotic disease allows construction of pedal bypasses especially by the
      use of short autologous vein grafts employing distal origin of the bypass.
      Indication and performance of the bypass procedure rely on a complete
      angiographic evaluation of the arterial system of the diseased limb. Besides the
      dorsalis pedis artery with its major branches as preferentially used recipient
      vessel, the posterior tibial artery and its plantar branches may be anastomosed.
      Thus, improved foot perfusion will allow necessary minor amputations with safe
      wound healing. The use of autologous vein grafts is associated with a high late
      patency rate of more than 70% and a late limb salvage rate of more than 80%.
      Pedal artery bypass grafting should routinely be part of the therapeutic
      strategies in advanced diabetic foot syndrome with critical limb ischemia and
      impending limb loss.

PMID- 11977583
TI  - Assessment of neonatal tetanus elimination, Namibia.

PMID- 11977584
TI  - [Molecular biological progress of hepatocyte growth factor (HGF)].
AB  - Hepatocyte growth factor (HGF) is a multifunctional growth factor which is a
      heterodimeric glycoprotein molecule. There are three truncated HGF variants: NK1,
      NK2, NK4. The structure of the promoter of HGF is very complicated, and the
      expression of HGF is regulated by various factors and regulatory elements.
      Because of the importance of HGF to human body, the genetic engineering
      expression and gene therapy investigation of HGF are being done.

PMID- 11977585
TI  - [Bioactive compounds from marine sponges and cell culture of marine sponges].
AB  - Presented a survey of bioactive compounds discovered from marine sponges in the
      recent five years, including the classes, distribution and their potential
      pharmaceutical uses. In particular, the compounds with antitumor, antivirus and
      antibacteria activity were discussed with their originating marine sponge
      species. Whereas the "Supply Problems" were identified to hinder the clinical
      tests and commercial applications of most of the sponge bioactive compounds. In
      vitro cell culture of marine sponges is one of the most promising approaches to
      solve this problem. The state-of-the art of marine sponge cell culture and the
      challenging areas were discussed. A brief summary of the R&D status was also
      given on the bioactive compounds from marine sponges in Chinese oceans. It is
      crucial to invest more efforts on studying marine sponges and their bioactive
      compounds in our country in order to develop new marine drugs of independent
      intellectual property.

PMID- 11977586
TI  - [Genome analysis of transgenic homozygous line "Minghui 63-Xa21"].
AB  - By using rice SSRP, RAPD and AFLP molecular markers, the genome of rice
      transgenic line "Minghui 63-Xa21" was analyzed. 32 SSRP primers, 42 RAPD primers
      and 8 AFLP primers could produce obvious PCR bands in the analysis of at least 12
      individual plants selected randomly from "Minghui 63-Xa21" T3 generation. Totally
      550 PCR bands, equivalent to 550 genomic sites, were detected. Different
      individual plants of the transgenic homozygous line displayed almost the same PCR
      pattern. Compared with the control "Minghui 63", no difference was found in their
      PCR patterns. This indicated that the introduction of Xa21 into the genome of
      "Minghui 63" did not change these 550 genome sites and their heredity. Very few
      variant PCR bands were observed in some individual plants from both "Minghui 63
      Xa21" and "Minghui 63". However, the variant percentage was equivalent between
      the transgenic line and the non-transgenic control line.

PMID- 11977587
TI  - [Cloning and expression of Buthus martensii Karsch scorpion toxin gene (BmK IT3)
      in Escherichia coli].
AB  - According to the reported sequence of Buthus martensii Karsch scorpion toxin gene
      (BmK IT3), we synthesized two primers, which were complementary in a region. By
      the means of PCR, we got the gene. The gene was fused in expression vector pET
      28a, which gave rise to a recombinant plasmid pET(IT3R). Then it was transformed
      into E. coli BL21 (DE3). With IPTG induction, the gene was efficiently expressed.
      And the fusion product was soluble.

PMID- 11977588
TI  - [Attachment and growth of cultured fibroblast cells on chitosan/PHEA-blended
      hydrogels].
AB  - The chitosan/PHEA-blended hydrogels were prepared from PHEA and chitosan in
      various blend ratios. The water contents of the hydrogels were in the range of
      50%-80% (wt). The attachment and growth of fibroblast cells(L929) on the
      hydrogels were studied. The results indicated the PHEA content in hydrogels has
      great effect on cell attachment but has little effect on the growth of L929
      cells.

PMID- 11977589
TI  - [Cloning of 5', 3' flanking sequence of ovine BLG and regulating the expression
      of GFP in mammary gland cell line].
AB  - 5' and 3' flanking region of ovine BLG were amplified from sheep genomic DNA
      according to the published whole sequence of ovine BLG and cloned to pGEM-T
      vector correspondently. By partially sequencing, the sequences of BLG 5' and 3'
      flanking were the same as that of publication completely. The recombinant
      structure used to direct exogenous gene especially to express in mammary gland
      was constructed by joining 4.2 kb 5' flanking with 2.1 kb 3' flanking. In order
      to assess the efficiency of BLG regulatory elements, green fluorescent protein
      (GFP) gene as a reporter was fused with BLG construct and transfected the mammary
      epithelial cells (TD47). Through observation under UV microscope and detection by
      fluorometer, it is demonstrated that the GFP has been successfully expressed in
      TD47 cell line. By virtue of direct observation and quantitative analysis, the
      BLG-GFP construct can be served as a model for the quick assessment of mammary
      gland expression construct.

PMID- 11977590
TI  - [Strategies of functional analysis of new genes].
AB  - Functional analysis of new genes is playing a central role in postgenomic era.
      Here we reviewed several main strategies including bioinformatics, gene
      transduction, antisense technology, certain gene silence induced by RNA
      interference (RNAi), transgene and gene knockout and artificial chromosome
      transduction.

PMID- 11977591
TI  - [The thinking about modern biological technology].
AB  - The way of life and mode of thinking of mankind is being changed by modern
      biological technology. It may be come true again that coexist and evolution of
      man and nature because the development of modern biological technology, but it
      also cannot avoid produce some new problem which made people have a think deeply
      to biological warfare, ethics and morals, law, society, food safety, production
      of industry and agriculture, energy resources, environment.

PMID- 11977592
TI  - [Na+/H+ antiporter and plant salt tolerance].
AB  - Na+/H+ antiporter plays an important role in mechanisms of the plant salt
      tolerance, it extrudes Na+ from cell energized by the proton gradient generated
      by the plasm membrane H(+)-ATPase and/or compartmentalizes Na+ in vacuole
      energized by the proton gradient generated by the vacuolar membrane H(+)-ATPase
      and H(+)-PPiase. This review mainly discusses the latest progress in the study of
      Na+/H+ antiporter in plant and yeast at molecular level.

PMID- 11977593
TI  - [Couple production of human calcitonin and rat peptidylglycine alpha-amidation
      monooxygenase in insect cells].
AB  - Human calcitonin (hCT) is a 32 amino acid peptide hormone that requires C
      terminal amidation for full biological activity. Calcitonin has important
      physiological function in vivo. We describe the couple expression of a
      synthesized modified human calcitonin(hmCT) gene fused with glutathione-S
      transferase and rat peptidylglycine alpha-amidation monooxygenase (PAM) in insect
      cells infected by recombinant baculovirus GSTCT/PAM. Using Western blotting
      against hmCT or rat PAM, the GSThmCT fusion protein had been identified as well
      as the PAM. Following affinity chromatography with glutathione agarose column,
      the GSThmCT fusion protein produced by insect cells was purified. The purified
      fusion protein was also interacted with antibody against hmCT. The couple
      expression of a modification enzyme and its substrate in eucaryotic expression
      system may be used for producing other biological activity peptides.

PMID- 11977594
TI  - [The construction of the hammerhead ribozyme genes targeting against apple scar
      skid viroid and its activity detection in vitro].
AB  - The genes of short armed hammerhead ribozyme targeting against two sites on
      positive strand (194-196) and negative strand (89-91) of ASSVd were designed,
      synthesized and cloned according to the action manner of hammerhead ribozyme. The
      full lengths of the genes are 42 bp (RzASSVd(+)) and 40 bp (RzASSVd(-)). After
      transcription in vitro, the ASSVd positive and negative RNA labeled with 32P were
      mixed with the ribozyme transcript and incubated 3-4 h at 50 degrees C or 37
      degrees C. The results were assayed on 8% PAGE (containing 8 mol/L urea) and
      autoradiogrammed. As predicted, the transcript of the active RzASSVd(-) could
      cleave the ASSVd negative strand RNA with a high activity but had no cleavage
      effect on the ASSVd positive strand. The transcript of the RzASSVd(+) gene could
      cleave the ASSVd positive strand but its cleavage activity was very low. As the
      same, it cannot cleave the negative strand either. On the base of the result, we
      construct dimmer ribozyme gene pGEMRzASSVd(+/-) containing both RzASSVd(+) and
      RzASSVd(-).

PMID- 11977595
TI  - [Expression of human interleukin-11 in cell culture and larvae of silkworm].
AB  - A recombinant transfer vector, pBacIL-11, containing hIL-11 cDNA of 546
      nucleotides lacking leader sequence was constructed and co-transfected into BmN
      cells with linearized BmBacPAK(modified BmNPV) DNA for construction of a
      recombinant baculovirus carrying the hIL-11 gene. Southern hybridization analysis
      suggested that the recombinant baculovirus DNA contained hIL-11 cDNA fragment.
      RNA dot blotting demonstrated that the hIL-11 gene was transcribed. The
      recombinant baculovirus has a strong infectivity to BmN cell line and to silkworm
      larvae and pupae. Specific hIL-11 bands were detected from all the samples of
      cell extract, culture supernatant, haemolymph of larvae and pupae by SDS-PAGE
      analysis. Biological activity of the expressed product was determined with IL-11
      dependent B9-11 cell line and by MTT colorimetric assay, which indicated that
      biologically active rhIL-11 protein was overexpressed in BmN cell line and in
      silkworm larvae and pupae.

PMID- 11977597
TI  - [Expression of the human soluble low density lipoprotein receptor in
      methylotropic yeast].
AB  - To obtain the expression of human low density lipoprotein receptor ligand binding
      domain in methylotropic yeast, firstly the DNA fragment encoding for human low
      density lipoprotein receptor ligand binding domain was amplified by RT-PCR with
      human hepatoma Bel-7402 total RNA as template. The nucleotide sequencing analysis
      indicated that the sequence of the cloned DNA fragment was as same as the
      reported human LDLR cDNA sequence. Then the expression vector pPIC9K-sLDLr was
      constructed, linearized and introduced into Pichia pastoris GS115 by
      electroporation. The recombinant sLDLR was identified by SDS-PAGE, Western blot
      and Ligand binding blot in supernatant of GS115/pPIC9K-sLDLr. The SDS-PAGE and
      Western blot analysis showed that the apparent molecular weight of expressed
      sLDLR was about 36 kD. And the ligand binding blot analysis indicated the
      expressed sLDLR has the biological activity. The sLDLR, which had the biological
      activity, was successfully secretorily expressed in the Pichia pastoris (GS115).

PMID- 11977596
TI  - [Cloning and expression of extracellular domain of prostate specific membrane
      antigen in Escherichia coli and preparation of polyclonal antibody].
AB  - Human Prostate Specific Membrane Antigen(PSMA) cDNA was amplified using total RNA
      extracted from prostate carcinoma tissue by RT-PCR. The cDNA fragment of
      extracellular domain of PSMA(edPSMA) gene was amplified by PCR and cloned into
      expression vector pMAL-c2x. Sequence analysis of both PSMA and edPSMA revealed
      identity to the GenBank reported. The edPSMA was expressed in E. coli as part of
      a fusion protein with MBP as the induction of IPTG. Western blot analysis showed
      the recombinant protein could react with PSMA monocloned antibodies 4G5. MBP
      edPSMA fusion protein were purified by amylose resin affinity chromatography and
      showed to be homogeneity in SDS-PAGE(120 kD). BALB/C mice were immunized with the
      purified protein for the preparation of polyclonal antibody. The polyclonal
      antibody, which had a title of 1:12,800, were indicated the specificity to
      prostate tissue.

PMID- 11977598
TI  - [Nucleotide sequence and protein sequence analysis of GL-7-ACA acylase from
      Pseudomonas sp. 130].
AB  - The nucleotide sequence and N-, C-terminal amino acid sequences of alpha,beta
      subunit of glutaryl 7-ACA acylase C130 from Pseudomonas sp. 130 were determined.
      The alignment of the acylase C130 with the other acylases shows that it has high
      homology with the acylases from Pseudomonas sp. GK16 and C427, but low homology
      with the others. There is large difference in the N-terminal of alpha-subunit,
      while the N-terminal of beta-subunit has significant conservation.

PMID- 11977599
TI  - [Avirulence genes of plant pathogens].
AB  - One type of important plant disease resistance, gene-for-gene resistance, is
      resulted from the interactions between products of the pathogen avirulence (Avr)
      genes and their matching plant resistance (R) genes. Avr genes have been cloned
      from a variety of pathogens including fungi, bacteria, viruses and oomycetes. No
      significant homology is found between sequences of the most cloned Avr genes and
      those of known proteins or between those of themselves. However, significant
      homology has been found between sequences of the cloned R genes and those of
      known proteins or between those of themselves. R proteins consist of similar
      domains. It has been reported that hypersensitive cell death and resistance,
      which are induced by interactions between products of different Avr/R gene pairs
      consisting of similar R genes but different Avr genes, are distinct in
      development speed, strength, and organ and tissue specificity. Avr genes have
      dual functions: Pathogens containing Avr genes are avirulent to plants carrying
      the matching R genes, while they are virulent in race, strain, pathovar or
      species-specific way to plants without carrying the matching R genes.

PMID- 11977601
TI  - [Study on production of acrylamide by microbial method (I)--Culture of bacterium
      cells and expression of high activity of nitrile hydratase].
AB  - The cultural conditions for the growth of Norcardia cell were studied in this
      paper. Controlling pH value, adding nutrient and optimizing the quantity of
      inducer during cultivation, the activity of nitrile hydratase reached 6567 u/mL
      (culture medium), which was the highest value appeared in native journals. In the
      farther hydratase experiments, no by-product, crylic acid, was detected. It
      showed that the activity of amidase was not promoted obviously while the activity
      of nitrile hydratase was increased greatly. The results set a strong foundation
      for the industrial application and the research on new technology.

PMID- 11977600
TI  - [Extraction of the salt-tolerant cDNA in mangrove Avicennia marina by mRNA
      differential display].
AB  - RNAs of the leaves in Avicennia marina, which cultured in 50@1000 and 0@1000
      salinity condition respectively, were isolated for mRNA differential display
      analysis. Screened by OligodT12 GC and eight 10-oligonucleotide arbitrary
      primers, differential cDNA fragments-csrg1(600 bp), csrg2(550 bp), csrg3(480 bp),
      only appeared in the leaves of Avicennia marina cultured in 50@1000 salinity
      condition. After detected by RNA dot hybridization, only csrg1 appeared the
      difference between the RNAs of the leaves in Avicennia marina cultured in 50@1000
      and 0@1000 salinity condition respectively, and csrg1 was confirmed as the salt
      tolerant cDNA. csrg1 was cloned and sequenced. After searching in Genbank, there
      were no similar sequences reported.

PMID- 11977602
TI  - [Effect of trypsin on the rat keratinocyte separation and subculture].
AB  - The effect of trypsin on the separation an subculture of the keratinocytes was
      investigated in this work. It was found that when 0.25% trypsin was employed for
      5 minutes to separate keratinocytes, the number of active keratinocytes and the
      cells capable of forming colony were higher than those of other experimental
      conditions. The maximum attached ratio of primary keratinocytes was obtained when
      skin tissues were treated at 0.05% concentration of trypsin. With the increase of
      the trypsin concentrations, the attached ratio, attachment rate constant, and
      colony forming efficiency were all increased. Thus, 0.25% concentration of
      trypsin was recommended for separating and subculturing the keratinocytes.

PMID- 11977603
TI  - [Cloning and expression of a thermostable beta-glycosidase gene from Thermus
      nonproteolyticus HG102].
AB  - The gene coding for beta-glycosidase (EC3.2.1.21) from Thermus nonproteolyticus
      HG102 has been cloned and expressed in E. coli. The gene open reading frame was
      1311 bp and it codes for 436 amino acids. The deduced amino acid sequence of the
      enzyme showed identity with members of glycosyl hydrolase family I. The enzyme
      had high content of hydrophobic amino acid (Ala 12.8%, Leu 10.9%), Arg(9.6%),
      Glu(9.4%) and Pro(8.0%), but low content Cys(0.45%) and Met (0.9%). From the
      alignment of enzyme amino acid sequence with other glycosyl hydrolase family I
      members, Glu164 and Glu338 were predicated as the proton donor and nucleophile
      group. The DNASTAR program was used to predict the secondary structure. According
      to the Chou-Fasman model, the enzyme has 41.4% of alpha-helics, 16.2%, beta
      strands, 14.4%, beta-turns. 14 of the 35 Pro were located at the second sites of
      beta-turns. Hydrophobic interaction, ion bond, alpha-helics and Pro had important
      contribution to Tn-gly thermostability.

PMID- 11977604
TI  - [Hairy-root culture of Polygonium multiflorum Thunb. and the production of its
      active constituents-anthraquinones].
AB  - Transformed hairy roots of Polygonium multiflorum Thunb. were obtained by the
      transformation of Agrobacterium rhizogenes LBA9402. It was clearly demonstrated
      that T-DNA of A. Rhizogenes Ri plasmid was integrated into the cells of hairy
      roots by the experiments of PCR and Southern hybridization. Through the screen of
      basic medium and the research of growth curve of hairy roots, the optimum
      inoculum time was selected in 30 days or so in the optimum condition-MS medium.
      On the condition, the content of rhein was 2.85 folds higher in hairy roots than
      that of natural plants by means of HPLC.

PMID- 11977605
TI  - [Studies on the optimal expression condition, purification and its
      characterization of ScFv-2F3].
AB  - The expression vectors of the gene encoding ScFv-2F3 were transformed into E.
      coli BL21(DE3). Clones of higher expression were first selected, then were grown
      in the presence of IPTG at 37 degrees C to induce its expression. The culture
      conditions were carefully optimized. It was found that optimal conditions were as
      follows: the induction was started as OD590 reached to 1.0-1.8; the concentration
      of IPTG was 0.3-0.5 mmol/L and induction time is 7 h. The yield of ScFv-2F3
      expressed in the selected clones is about 20% of the total proteins. The optimal
      culture conditions were successfully applied to fermenter of 50 L. The conditions
      of washing the inclusion bodies were also optimized. A two-step method was used
      to renature the inclusion body. The expression product of interest and its
      biological activities were characterized with Western blotting and ELISA. A novel
      selenium-containing single-chain abzyme with GPX activity was prepared.

PMID- 11977606
TI  - [Cloned goats produced from the somatic cells of an adult transgenic goat].
AB  - This study was carried out to examine the effect of different donor cell type and
      micro-manipulation on the development of reconstituted embryos. Cultured mural
      cumulus cells or fibroblast cells from an adult transgenic goat expressing human
      erythropoietin(rhEPO) were used as the donor cells in nuclear transfer
      experiments. The reconstituted eggs were generated by transferring fibroblast
      cells or cumulus cells into the perivitelline space of enucleated M II oocytes
      and then followed by electrofusion and activation. After 6 days' incubation in
      vivo, the reconstructed embryos developed into morulae or blastocysts were
      transferred into 6 foster recipients. Two of the foster-mothers were pregnant and
      gave birth to two offspring, which were derived from the fibroblast cell and
      cumulus cell, respectively. Fingerprint analysis showed that the PCR-RFLP
      patterns of the two offspring were identical to that of donor goats. PCR results
      indicated that these cloned goats carried hEPO gene as same as their donor cells.

PMID- 11977607
TI  - [Enzymatic synthesis of monoglycerides in microaqueous media by using lipase from
      Pseudomonus fluorescens].
AB  - Enzymatic synthesis of monoglycerides by glycerolysis of oil and fats in
      microaqueous solvent-free media was investigated by using lipase from pseudomonus
      fluorescens (PFL). Initial eutectic point(IEP) was substituted for melt point of
      oil and fats in Critical Temperature Theory. By investigating the glycerolysis
      under different IEP, it is showed that there is a relationship between
      composition of the oils and the yield of monoglycerides: Y = -0.0006 X3 + 0.0592
      X2 - 0.8909 X + 26.753(13% < X < 76.5%), here X is the contents(W/W) of saturated
      fatty acid residue (C16 + C18) in the oils, Y is the yield of monoglycerides at
      40 degrees C. The optimum isothermal reaction conditions for a system which IEP
      is 40 degrees C are: 40 degrees C, 3%-4.5% (W/W) water in glycerol, dosage of
      lipase is 500 u/g oil when the mole ratio of glycerol to oil is 2.5:1. The
      highest yield of monoglycerides is 81.4% in 48 h by means of programming
      temperature reaction.

PMID- 11977608
TI  - [Continuous biosynthesis of epoxypropane in a methanotrophic attached-films
      reactor].
AB  - Using a fluidized bed as immobilization system, mixed culture methanotrophic
      attached-films were developed on diatomite particles. The Methane Monooxygenase
      (MMO) activity was found to increase obviously as soon as the lag phase ended.
      Greater than 90% of the MMO activity in the bed was attached. Biofilm
      concentration of 3.3-3.7 mg dry weight cell/g DS was observed. Batch experiments
      were performed to explore the possibility of producing epoxypropane by a
      cooxidation process. The effect of methane on the oxidation of propene to
      epoxypropane and the effect of propene on the growth of methanotroph were also
      studied. In continuous experiments, optimum mixed gaseous substrates (methane:
      35%; propene: 20%; oxygen: 45%) were continuously circulated through the
      fluidized bed reactor to remove product. Initial epoxypropane productivity was
      110-150 mumol/d. The bioreactor operated continuously for 25 d without obvious
      loss of epoxypropane productivity.

PMID- 11977609
TI  - [Studies on lipase-catalyzed synthesis of ethylglucoside lactate in non-aqueous
      phase].
AB  - Ethylglucoside lactate, a novel Alpha-Hydroxy Acids Derivative, was synthesized
      by transesterification in non-aqueous phase using immobilized lipase as
      biocatalyst. Based on the studies of the factors effecting initial rate and
      conversion under atmospheric pressure (solvent, acyl donor, different immobilized
      lipase, substrate concentration, enzyme concentration and temperature), the
      results show that solvent-free medium using butyllactate as acyl donor is
      suitable to the ester synthesis. The reaction conditions have been optimized as
      the following: the amount of enzyme = 75 g/L, the ethylglucoside concentration =
      0.4 mol/L, 70 degrees C, 200 r/min, 50 h, which the conversion was 71%. A 90%
      conversion and a 60.7 mmol.L-1.h-1 initial rate can be obtained under reduced
      pressure, which the conditions are enzyme 75 g/L, ethylglucoside 0.35 mol/L, 65
      degrees C, 200 r/min and 40 h. The product purified by extraction and SIO2
      chromatography was identified by infrared spectroscopy and 1H NMR.

PMID- 11977610
TI  - [Visualization of the interaction between IL-6 and IL-6R by imaging
      ellipsometry].
AB  - Imaging Ellipsometry is one of recently developed optical surface-sensitive
      methods for the investigation of various aspects of biomolecules adsorption on
      solid surfaces and biomolecules interactions. It has advantages of high
      sensitivity to layer-thickness, big area of view, high sampling speed, and high
      lateral resolution. Compared with other solid phase methods such as enzyme linked
      immunosorbent assay, immunofluorescence and radioimmunoassay, imaging
      ellipsometry has the advantage of not involving any labelling of reactants and it
      is a relatively inexpensive method and easy to handle. In this report, the mono
      layers of IL-6 and IL-6 receptor were visualized as well as their interaction.

PMID- 11977611
TI  - [In vitro chondrogenic phenotype differentiation of bone marrow stem cells].
AB  - OBJECTIVE: To investigate the feasibility of chondrogenic phenotype
      differentiation of adult swine bone marrow stem cells(MSCs) in a defined medium
      as seeding cells in cartilage tissue engineering. METHODS: A volume of 5 ml bone
      marrow was aspirated from swine iliac crest and cultured in the complete medium
      of DMEM-LG for two weeks. The growth and ultrastructure of the cultured MSCs were
      observed. Immunohistochemistry and in situ hybridization were applied to detect
      the expression of collagen type II. RESULTS: The MSCs changed from a spindle-like
      fibroblastic appearance to a polygonal shape when transferred from the complete
      medium of DMEM-LG to a defined medium. A large amount of endoplasmic reticulum
      was observed in large Golgi ccmplex and mitochondria. The differentiation of MSCs
      toward chondrogenic phenotype was verified by the positive result of collagen
      type II through immunohistochemistry and in situ hybridization respectively.
      CONCLUSIONS: Bone marrow stem cells obtained from adult swine can differentiate
      to be chondrogenic phenotype when cultured in vitro. MSCs can likely be served as
      optimal autogenous cell source for cartilage tissue engineering.

PMID- 11977612
TI  - [The application of septum cartilage in correcting of the unilateral cleft lip
      nasal deformity].
AB  - OBJECTIVE: To explore an ideal method for comprehensive correcting of the
      unilateral cleft lip nasal defomity. METHODS: The operation includes replacement
      of the displaced tissue, excision of the deviated septum, and correction of the
      deviated septum and the deformity of the lower nose. The excised nasal septum was
      grafted on the alar base, the nasal columella and the nasal tip. RESULTS: 32
      patients were treated with this method from 1994 to 1999. Postoperative fellow-up
      for 1-3 years demonstrated satisfactory results. CONCLUSION: Through excision and
      grafting of the nasal septum, the deviated septum and the deformity of the lower
      nose are effectively corrected. Complete undermining and replacement of the
      displaced structure are the basis of correcting the cleft lip nasal deformity.

PMID- 11977613
TI  - [Diagnosis and treatment of congenital recessive cleft palate].
AB  - OBJECTIVE: To explore an effective method to diagnose and treat the congenital
      recessive cleft palate. METHODS: For the treatment of congenital recessive cleft
      palate, an operation was designed to recover the anatomic length and function
      mobility of the soft palate. The operation procedure includes incising vertically
      the midline mucous membrane of the soft palate, creating and pushing back the
      mucosal flap of the hard palate, making Z-plasty on the nasal mucosa,
      reconstructing the sling of the levator veli palatini muscle and repairing the
      palatal defects with the buccinator muscularis mucosae flap. 12 cases of
      congenital recessive cleft palate have treated with this method. RESULTS: All of
      the 12 cases obtained good results. Their pronunciation improved obviously.
      CONCLUSION: The method is effective for diagnosis and treatment of congenital
      recessive palate, which is worthy of further application.

PMID- 11977614
TI  - [Rhinoplasty of unilateral cleft lip].
AB  - OBJECTIVE: To investigate the technique for unilateral cleft lip nasal
      deformities. METHODS: Through the traditional columella margin incision, the alar
      cartilage and the lateral nasal cartilage were exposed. After the mucosa between
      the two cartilages was divided, a mucosa-cartilage flap was developed and
      anchored, moving the lateral crus upwardly and medially, correcting the nasal
      deformity. RESULTS: 52 cases of primary nasal deformities and 18 cases of
      secondary nasal deformities were corrected with this technique. Satisfactory
      results were achieved. CONCLUSION: This technique is recommendable, which is more
      likely to restore the physiological characters of the nose than the conventional
      technique.

PMID- 11977615
TI  - [Effects and mechanism of ischemic preconditioning on the survival of axial flaps
      in rats].
AB  - OBJECTIVE: This study was to develop a new method that can improve flap survival.
      METHODS: A long skin flap spanning the full length of the rat dorsum was used to
      make a bilateral skin tube, which was based on the lateral thoracic artery
      proximally, and the deep circumflex iliac artery distally. The animals were
      randomly divided into 3 groups of 8 rats in each group: the control and two
      experimental groups with elevation of the tube (the proximal pedicle divided)
      immediately or 24 hours following ischemic preconditioning. All tube flaps were
      observed for 3 days postoperatively and the surviving flap area was measured as a
      percentage of the whole flap using the paper template technique. Heat shock
      protein 70 in the three groups was examined by means of immunohistochemistry.
      RESULTS: There was an overall statistical significance in comparison of flap
      survival of the preconditioned flaps with that of the controls. There was no
      statistical significance between the two preconditioned groups. Heat shock
      protein 70 (HSP70) was demonstrated immunohistochemically in the preconditioned
      skin flap but not in the control skin flap. CONCLUSION: Ischemic preconditioning
      can improve skin flap survival and the contents of HSP70. It is suggest that the
      mechanism be related to the function of HSP70.

PMID- 11977616
TI  - [Clinical application of a retrograde nasolabial fold island flap based on the
      upper lip artery].
AB  - OBJECTIVE: To explore a new method for enlarging the rotation range of the
      nasolabial fold flap. METHODS: We designed a retrograde nasolabial fold island
      flap pedicled with the upper lip artery for repairing facial defects. The anatomy
      of the upper lip and the vascular supply to the nasolabial skin were observed.
      RESULTS: All the flaps in 7 cases survived completely with satisfactory results.
      CONCLUSION: The retrograde nasolabial fold island flap pedicled with the upper
      lip artery enlarged the rotating range of the nasolabial fold flap. The flap is
      recommendable for its consistent pedicle and abundant vascular supply.

PMID- 11977617
TI  - [The reverse medialis pedis flap for coverage of forefoot skin defects].
AB  - OBJECTIVE: To study a new method to repair forefoot skin defects. METHODS: Based
      on anatomical studies, a reverse medialis pedis flap was designed for coverage of
      forefoot skin defect. The flap was based on the distal end of the medial plantar
      artery and had distal anastomosis with the lateral plantar artery and dorsal
      metatarsal artery. RESULTS: The flap was used clinically in 6 cases. The size of
      the flap ranged from 4 x 3 cm to 11 x 9 cm. The pedicle of the flap was 6 to 11
      cm. All flaps survived completely. The aesthetic and functional results were
      satisfactory after 6-24 months follow-up. CONCLUSION: The flap is one of the best
      choices for repairing of forefoot skin defects.

PMID- 11977618
TI  - [Experimental study on enhancement of tissue expansion with papaverine cream].
AB  - OBJECTIVE: To evaluate the effect of external use of papaverine cream on
      enhancement of tissue expansion. METHODS: 8 mini pigs were randomly divided into
      4 groups. During inflation, papaverine was given externally in group A, through a
      delivery system in group B, though intramuscular injection in group C. Papaverine
      was not given in group D. The time of inflation, the expansion rate, the
      surviving length of expanded flaps and the papaverine concentration in the
      fibrous capsule in each group were examined. Histologic and electroscope
      examinations of the expanded tissue were made. RESULTS: The average inflation
      time was 28.9 +/- 4.5 days in group A, 34.0 +/- 2.6 days in group B, 37.6 +/- 4.8
      days in group C and 38.5 +/- 3.5 days in group D. There was significant
      difference between each group(P < 0.05). The average surviving length of expanded
      flaps in group A was 13.67 +/- 1.28 cm, 11.07 +/- 0.88 cm in group B, 10.79 +/-
      0.49 cm in group C, and 9.49 +/- 0.77 cm in group D. There was significant
      difference between each group (P < 0.01). Histologic examinations of the expanded
      tissue suggested that there were no significant differences in thickness of
      epidermis, derma and fibrous capsule among the four groups. Electroscope
      examinations of the myofibroblast in fibrous capsule showed that there were
      smaller nuclei, fewer microfilaments and fewer mitochondrias and rougher
      endoplastic reticulume in group A than those in other groups. The concentration
      of papaverine in fibrous capsule of group A was 3.5 +/- 1.2 micrograms/g.
      Papaverine was detected neither in the skin of other groups nor in the blood of
      all groups. CONCLUSIONS: 1. Papaverine cream can permeate through skin and
      maintain high concentration and continuous effect in local tissue. 2. External
      use of papaverine cream can inhabit the function of myofibroblast in fibrous
      capsule, increase inflation rate, accelerate expansion process, and improve
      microcirculation of the expanded skin with a result of prolongation of surviving
      length of expanded flaps. 3. The technique of enhancing tissue expansion with
      external use of papaverine has the advantages of convenient delivery, cheapness,
      no more injury and infection, and no side effects etc. It is a safe, effective,
      simple, and reliable method for accelerating tissue expansion.

PMID- 11977619
TI  - [Experimental study on the change and effect of TGF-beta 1 after skin expansion].
AB  - OBJECTIVE: To study the injury process of the skin due to expansion. METHODS: New
      Zealand rabbits were divided into 4 groups: rapid expansion and slow expansion as
      well as two control groups. The changes of skin TGF-beta 1 were observed
      immediately after expansion and at 1, 12, 24 weeks after expansion.
      Immunohistochemistry and in situ hybridization technique were applied. RESULTS:
      TGF-beta 1 increased in the skin immediately after expansion. In groups of rapid
      expansion, TGF-beta 1 increased faster and then decreased also faster than slow
      expansion groups. The results from immunohistochemistry and in situ hybridization
      were almost same. CONCLUSION: Expansion resulted in skin injury. Rapid expansion
      injured the skin more seriously than slow expansion. TGF-beta 1 may be the main
      regulating factor to repairing process.

PMID- 11977620
TI  - [The application of arterialized venous digital island flap in fingertip
      reconstruction].
AB  - OBJECTIVE: To introduce an operation for fingertip reconstruction. METHODS: The
      vascularity of the reverse dorsal island flap is augmented by performing an
      arteriovenous anastomosis between the dorsal vein in the flap and a digital
      artery at the fingertip. The flap was used in ten patients for reconstruction of
      their fingertip defects. RESULTS: All the ten flaps survived and the appearance
      was good. CONCLUSION: The method is easy except for the necessity of performing
      standard microvascular surgery. The flap is a good option for repairing fingertip
      defects.

PMID- 11977621
TI  - [The experimental study of bioabsorbable mini-plate for rigid fixation on
      rabbits].
AB  - OBJECTIVE: To study the biodegradation process of the bioabsorbable mini-plate
      (LactoSorb) and its influence on bone healing. METHODS: 15 mature New Zealand
      White Rabbits were selected as the experimental animals. The bilateral zygomatic
      arch were fractured using a fissure bur. One side was fixed with the
      bioabsorbable mini-plate and the other side was fixed with Titanium mini-plate as
      a control. 5 animals were killed after 4, 12, and 24 weeks post operation
      respectively for radiographic and histologic study. RESULTS: At 4 weeks, the
      absorbable plate changed from transparent to opaque and its dimensions was
      enlarged. The bone gaps of both groups were filled with new bone. No inflammatory
      cells were found in both groups. At 12 weeks, the absorbable plate broke to small
      pieces or particles, its dimensions reduced greatly but the outline could still
      been recognized. The bone continuity had been reestablished in both groups. At 24
      weeks, the absorbable plate was resorbed completely. Only the residual screw
      could be seen in the screw hole. Complete bone healing was seen in both groups.
      No histological differences of bone healing were found at this stage. CONCLUSION:
      The absorbable plate demonstrates excellent biocompatibility. No adverse local
      inflammatory reactions were found during the plate was absorbed gradually. In the
      non-weight baring area, the absorbable plate provides the same fixation stability
      as that of the metal plate.

PMID- 11977622
TI  - [Improved technique for macrocheilia].
AB  - OBJECTIVE: To introduce an improved technique for Macrocheilia. The traditional
      technique for macrocheilia with direct suture and Z-plasty was improved to
      decrease postoperative complications, e.g. dynamic abnormality, obvious scar and
      recurrence due to scar contraction. METHODS: Outside of the new commissure, a
      triangle flap of the upper lip vermilion was designed, created and inserted to
      the lower lip. The orbicularis oris muscle was anatomically replaced. Skin Z
      plasty was made with triangle flap transferring from the upper to the lower
      instead. RESULTS: Since August 1985, the new technique has been used in 12 cases
      of Macrocheilia. All the patients obtained satisfactory results with nice
      configuration and good function without dynamic abnormality and obvious scar.
      CONCLUSION: The new technique is a more reasonable method for macrocheilia with
      nice configuration, good function and fewer complications.

PMID- 11977623
TI  - [One-stage repair of hypospadias using a scrotal septal skin flap based on peri
      meatus dartos fascia].
AB  - OBJECTIVE: To explore the feasibility of one-stage repair of hypospadias using
      scrotal septal skin flap based on peri-meatus dartos fascia. METHODS: Nine
      patients were repaired by this method. RESULTS: All patients achieved good
      results without urethral fistula or stricture. The angle of the penis to the
      scrotum is normal. CONCLUSION: The flap has reliable blood supply and the flap
      creation is easy. It is a simple, convenient and effective method for one-stage
      repair of hypospadias.

PMID- 11977624
TI  - [The double-ring, single-pedicle reduction plasty for gynecomastia].
AB  - OBJECTIVE: To investigate a new operation of breast reduction for gynecomastia.
      METHODS: In the past 5 years we treated 42 cases (80 sites) of gynecomastia with
      the double-ring incision, a supra-lateral derma-mammary pedicle of the nipple and
      areola and the tumescent technique. RESULTS: The tumescent anesthesia was
      effective. The operation was easily performed with slight injury and less
      bleeding. It was safe and the patients recovered quickly. 100 to 500 grams tissue
      was resected from one breast. There have been no severe postoperative
      complications, such as nipple or areola necrosis. Follow-up from 3 to 48 months
      showed satisfactory results except that there was mild scar hypertrophy on the
      incision around the areola. CONCLUSIONS: The new operation for gynecomastia with
      the double-ring incision, a supra-lateral derma-mammary pedicle of the nipple and
      areola, and the tumescent anesthesia is a good, reliable and convenient
      technique.

PMID- 11977625
TI  - [Experimental studies on histocompatibility of three bio-derived bones].
AB  - OBJECTIVE: To study the histocompatibility of three bio-derived bones. METHODS:
      After treatment with different physical and chemical method, three bio-derived
      bones, the composite fully deproteinized bone (CFDB), partially deproteinized
      bone (PDPB) and partially decalcified bone (PDCB) were implanted into rabbits.
      The toxicity, immune response and subperiosteum osteogenesis of CFDB, PDPB and
      PDCB were studied through gross observation, serum antibody measurement,
      evaluation of local cellular immune response and HE staining. RESULTS: The study
      showed that CFDB, PDPB and PDCB had no toxicity. They could conduct peripheral
      tissue to grow into them and had no harmful effect on subperiosteum osteogenesis.
      They could also promote cartilage and osteoid tissue derived from periosteum to
      calcify to new bone, and combine with the peripheral bone. The degree of immune
      response caused by them was in the sequence of PDCB > PDPB > CFDB. CONCLUSIONS:
      The three bio-derived bones, CFDB, PDPB and PDCB have good histocompatibility.

PMID- 11977626
TI  - [Cartilage engineering utilizing a porous bioceramic (beta-TCP)-cell complex].
AB  - OBJECTIVE: To evaluate the feasibility of growing tissue-engineered cartilage
      using chondrocytes seeded onto a biodegradable porous bioceramic, the beta
      tricalcium phosphate (beta-TCP). METHODS: A porous bioceramic template of beta
      TCP was created in the shape of a disc. Chondrocytes isolated from rabbit
      articular cartilage were seeded on the beta-TCP template and then kept in
      rotatory cell culture system (RCCS) for 1 week prior to subcutaneous
      transplantation into athymic mice. The three-dimensional structure was well
      maintained 16 weeks after implantation. After 4, 8, 16 weeks, the specimens were
      harvested and examined macroscopically, histologically and immunohistochemically.
      RESULTS: Gross morphological and histological analysis of the specimens from the
      chondrocyte-beta-TCP complex demonstrated new cartilage construction. The overall
      configuration of the experimental specimens closely resembled the structure of
      beta-TCP template. CONCLUSION: These findings suggest that porous bioceramic
      (beta-TCP) is a good "matrix" for chondrocyte, and can be used for cartilage
      engineering.

PMID- 11977627
TI  - [Local cytokines profile in gastric cancer lesions].
AB  - OBJECTIVE: To study the characteristics of local cytokines profile in human
      gastric cancer lesions and offer guides for immunotherapy of gastric cancer.
      METHODS: The cytokines profile in isolated CD4+, CD8+ T subsets and epithelial
      cells from cancer tissue, contrasted with benign gastric mucosa of 15 gastric
      cancer patients were analyzed by a highly sensitive radioactivity labeled semi
      quantitative reverse transcription polymerase chain reaction (RT-PCR) technique.
      RESULTS: The predominance of increased Th2 and reduced Th1 immune response in
      both CD4+ and CD8+ T subsets from cancer tissue, compared with benign gastric
      mucosa, were observed. IL-6, IL-8 and TNF-alpha in CD8+ T cells from cancer
      tissue showed statistical higher levels than those from benign gastric mucosa (P
      = 0.029, P = 0.022, P = 0.002), so did IL-10, TGF-beta, TNF-alpha in T cells and
      epithelial cells. CONCLUSION: A shift of Th1/Th2 cytokines to Th2 is found in T
      cells from local tumor lesion of gastric cancer, which suggests an immune
      suppressive status in local tumor lesion. The obvious change of cytokine profile
      in CD8+ T cell suggests they play a main role in immune suppression. To study the
      cytokine expression of different cell subsets, we are able to offer guides for
      immunotherapy for patients with gastric cancer.

PMID- 11977628
TI  - [Adhesion induces matrix metalloproteinase-9 gene expression in ovarian cancer
      cells].
AB  - OBJECTIVE: This work was conducted to investigate the expression of matrix
      metalloproteinase 9 (MMP 9) gene in cancer cells by fibronectin adhesion and the
      underlying mechanism of cell invasion. METHODS: Following adhesion of ovarian
      cancer cells A2780 to fibronectin, mRNA expression of MMP cells were assayed by
      reverse transcription-polymerase chain reaction (RT-PCR). MMP9 promoter was
      cloned from genomic DNA of HT1080 cells with PCR. The MMP-9-pGL2 reporter gene
      vector was constructed and then transiently transfected into A2780 cells.
      RESULTS: Adhesion induced the increase of cellular MMP9 mRNA content in A2780
      cells, not affecting the expression of MMP2 or TIMP-1 gene. The stimulation was
      enhanced with the increase adhesion time. When the transfected cells were allowed
      to adhere and spread on FN-coated surface, the promoter activity of MMP9 gene was
      also enhanced dramatically. CONCLUSION: Cell-ECM adhesion may stimulate the
      expression of MMP9 gene through stimulating the promoter activity, thereby
      enhancing cancer cell invasion and metastasis.

PMID- 11977629
TI  - [NF-kappa B expression in cholangiocarcinoma transfected with hepatitis C virus
      core gene].
AB  - OBJECTIVE: To study the role of hepatitis C virus (HCV) in the development of
      cholangiocarcinoma. METHODS: Recombinant plasmid of HCV-C gene constructed by
      molecular cloning technique was identified with restricting enzyme map. Then, it
      was transfected into QBC939 cells with lipofectin. After selection with G418, the
      resistant colonies were obtained and analysed by immunocytochemistry and Western
      blotting. Their morphology was observed by transmission electron microscopy
      (TEM). The expression of NF-kappa B was detected by immunocytochemistry. RESULTS:
      The results suggested that the recombinant plasmid was proved to carry the target
      gene by restricting enzyme map. Moreover, it could express HCV-C protein
      efficiently in QBC939 cells. The HCV-like particles were found in the cytoplasm
      by TEM, which were spherical with diameter of 50-80 nm possessing an outer
      membrane. Moreover, NF-kappa B activation was shown in HCV core gene-transfected
      cells. CONCLUSION: Because HCV-C gene could express steadily in
      cholangiocarcinoma cells, the transfected tumor cells (QBC939-HCVc) are an
      experimental model for studying the effect of HCV on the development of
      cholangiocarcinoma. The activation of NF-kappa B may be related to escape from
      immune surveillance and carcinogenesis of cholangiocarcinoma.

PMID- 11977630
TI  - [Mechanism of immune escape in renal cell carcinoma].
AB  - OBJECTIVE: To investigate the mechanism of immune escape in renal cell
      carcinoma(RCC). METHODS: Fas and FasL expressions were examined by
      immunohistochemical technique in 44 RCC patients, with the Ki67 expression and
      apoptosis of tumor infiltrating lymphocytes(TIL) monitored simultaneously.
      Cytokines including IL2 and IFN alpha were used to induce the expression of the
      renal carcinoma cell lines 786-0 cells. Combination treatment of 786-0 with
      cytokines and Anti-Fas monoclonal antibody (FasAb) was used to induce apoptosis.
      FasL function was assessed by in vitro co-culture assays using renal cancer cells
      786-0 and Fas-sensitive Jurkat T-cells. RESULTS: (1) Fas expression rate in
      RCC(22.8%) was lower than that in the controlled normal kidney tissues(53.8%, P <
      0.01). FasL expression rate in RCC (46.5%) was higher than that in the controlled
      normal kidney tissues (23.2%, P < 0.01). That of Ki67 was 32.8%, with the
      expressions of Fas and Ki67 showing a negative correlation (r = -0.62, P < 0.05).
      In contrast, the expressions of FasL and Ki67 showed a positive correlation. (r =
      0.93, P < 0.01). The Fas expression of stage I was significantly higher than that
      of stages III and IV. The expression rate of FasL in RCC was significantly
      increased with RCC stage (P < 0.01). (2) The apoptotic rate of TIL in RCC (33.9%)
      was significantly higher than that of the normal kidney tissues (3.5%, P < 0.01).
      The expression of FasL and the apoptotic rate of TIL in RCC gave a positive
      correlation (r = 0.96, P < 0.01). (3) Fas expression rate in 786-0 cells was
      13.7%. The apoptotic rate mediated by FAsAb was 9.6%. IFN alpha was able to up
      regulate the Fas expression and subsequently augment the FasAb-mediated apoptosis
      in 786-0 cells. But IL2 did not show similar effects. (4) The FasL expression
      rate of 786-0 was 18.6%. FasL expressed by 786-0 cells was able to induce
      apoptosis of Jurkat T-cells in co-culture assays and the apoptosis of Jurkat T
      cells was significantly lowered after blocking the effect of FasL with Fas
      neutralizing antibody NOK-2, giving the apoptotic rates of 14.9% and 2.0%,
      respectively, the difference therein is statistically significant (P < 0.01).
      CONCLUSION: Down-regulation of Fas expression and up-regulation of FasL
      expression are the mechanisms through which the RCC cells escape from immune
      attack.

PMID- 11977631
TI  - [Correlation between midkine protein overexpression and intrahepatic metastasis
      in hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the correlation between midkine (MK) protein expression
      with local infiltration and metastasis in human hepatocellular carcinoma (HCC).
      METHODS: Immunohistochemical and Western Blot analysis for MK were performed on
      samples of tumor tissue and the paratumor tissue from HCC and benign liver
      tumors. RESULTS: The overexpression of MK protein determined by
      immunohistochemical analysis was similar to that by Western Blot analysis. No
      specific positivity was detected in either benign liver tumor tissue or normal
      liver tissue, but most of HCC tissue showed a positive reaction to MK
      immunostain. No correlation between MK expression and other clinicopathological
      features in MK negative or positive HCC cases was found. Yet, the overexpression
      rate of MK protein in HCC with intra-hepatic metastasis was significantly higher
      than that in HCC without intra-hepatic metastasis. CONCLUSION: In human
      hepatocellular carcinoma, MK overexpressed at protein level may very well be
      closely related to local infiltration and metastasis.

PMID- 11977632
TI  - [Quantitive detection of multi-gene expressions and DNA content in the
      precancerous cells of esophageal carcinoma].
AB  - OBJECTIVE: To explore the molecular events and mechanism in the carcinogenesis of
      esophageal epithelium in the high incidence area of esophageal carcinoma.
      METHODS: Epithelial cells collected from the high incidence area of esophageal
      carcinoma were used to detect DNA content and ploidy by propidium iodide(PI)
      stain. The expressions of p53, p16 and cyclin D1 were stained by indirect
      immunofluorescence of fluorescein isothiocyanate(FTTC), which were detected by
      flow cytometry (FCM). RESULTS: During the process of carcinogenesis, DNA content
      increased significantly. The diploid cells decreased while heteroploid cells
      increased sharply, with a heteroploidy rate of 84.2%. At the same time, the p53
      protein accumulated and p16 was deleted. The positive rates of p53 and oncogene
      cyclin D1 were both 100%(5/5, 6/6) in the cancer group. CONCLUSION: In the early
      carcinogenesis of esophageal epithelium, DNA content and heteroploidy rates
      increase with tumor suppressor gene p16 deletion and p53 protein accumulation
      while oncogene cyclin D1 is overexpressed. Multiple molecular events have already
      occurred when esophageal carcinoma develops.

PMID- 11977633
TI  - [Expression of transcription factor T-bet/GATA3 in lung cancer patients and its
      interference by the traditional Chinese herbal medicine].
AB  - OBJECTIVE: To study the relation between the expression of transcription factor T
      bet/GATA3 and Th1/Th2 type cytokines in peripheral blood mononuclear cells (PBMC)
      from lung cancer patients and their interference by the traditional Chinese
      herbal medicine. METHODS: The gene expression of Th1/Th2 type cytokine IFN gamma,
      IL-2, IL-4, IL-6, IL-10, transcription factor T-bet/GATA3 and tumor tissue
      specific mRNA CEA, CK19 in PBMC from lung cancer patients were detected by
      reverse transcription-polymerase chain reaction RT-PCR. Meanwhile, the change of
      IFN gamma, IL-4, T-bet and GATA3 in PBMC before and after being cultured with the
      traditional Chinese herbal medicine-Astragulus and Tetramethylpyrazine was also
      observed. RESULTS: Predominant expression of Th2 type cytokines was detected in
      42 lung cancer patients. The positive rates of IL-4, IL-6, IL-10, IFN gamma and
      IL-2 were 27/42, 24/42, 31/42, 4/42 and 5/42, respectively. But, the positive
      rates of transcription factor T-bet and GATA3 were 16/42 and 34/42. Moreover, the
      expression intensity of T-bet was lower in the CEA and CK19 positive patients
      than the negative ones. On the contrary, the expression intensity of GATA3 was
      significantly higher in the same patients. CONCLUSION: Predominant expression of
      Th2 type cytokines may be related to lower expression of T-bet or higher
      expression of GATA3. This condition can be interfered by the traditional Chinese
      herbal medicine-Astragulus and Tetramethylpyrazine.

PMID- 11977634
TI  - [Expression of a novel immunoglobulin gene SNC73 in human cancer and its
      significance].
AB  - OBJECTIVE: To investigate the expression of a new immunoglobulin gene SNC73 in
      malignant tumor and normal tissue and its significance. METHODS: Expression level
      of SNC73 in tumors and normal tissues was determined by reverse transcription
      polymerase chain reaction and enzyme-linked immunosorbent assay (RT-PCR-ELISA) in
      90 malignant tumors, including colorectal cancer, gastric cancer, breast cancer,
      lung cancer and liver cancer. Analysis on relation of SNC73 expression with age,
      sex, site, differentiation grade, depth of invasion and metastasis of colorectal
      cancer was made to assess the clinical significance of SNC73. RESULTS: Mean ratio
      of SNC73 expression level in normal mucosa and colorectal cancer tissue was 7.134
      (P < 0.01). Expression of SNC73 showed no significant difference among gastric
      cancer, breast cancer, lung cancer or liver cancer as compared with the control
      normal tissues (P > 0.05). CONCLUSION: Down-regulation of SNC73 expression is a
      relatively specific phenomenon in colorectal cancer for which development SNC73
      may be a potential genetic marker. The study on relationship of SNC73 expression
      with development of colorectal cancer is promising.

PMID- 11977636
TI  - [Impact of micrometastasis in pathologically negative lymph node on staging and
      prognosis of non-small cell lung cancers].
AB  - OBJECTIVE: To study the influence of micrometastasis in lymph node on staging and
      prognosis of non-small-cell lung cancer (NSCLC). METHODS: In 39 NSCLC patients,
      micrometastasis in pathologically negative lymph nodes were tested through
      immunohistochemical cytokeratin (CK) analysis and the relationship between CK(+)
      and staging, survival were analyzed. RESULTS: In these 39 patients, the survival
      of CK(+) and CK(-) patients were 32 months and 48 months respectively (P =
      0.0178). Multivariate analysis of Cox regression model showed: clinical stage (P
      = 0.0288) and relapse or metastasis (P = 0.0053) affected the prognosis while
      micrometastasis in lymphnodes (P = 0.7740) did not. CONCLUSION: The detection of
      micrometastasis in the lymphnodes may serve as a supplement to the present
      staging system for lung cancer. Even though the prognosis of patients with
      micrometastasis being poorer than those without, micrometastasis in the lymph
      nodes should not be regarded as an independent prognostic factor.

PMID- 11977635
TI  - [1990-1992 mortality of stomach cancer in China].
AB  - OBJECTIVE: To assess the impact of stomach cancer on the Chinese population by
      epidemiological analysis of its mortality distribution. METHODS: 1990-1992 data
      on stomach cancer mortality collected by sampling survey involved one tenth of
      the total Chinese population. RESULTS: The crude mortality rate of stomach cancer
      in China was 25.2 per 10(5) (32.8 per 10(5) for males and 17.0 per 10(5) for
      females), which comprised 23.2% of the total cancer deaths from 1990 to 1992,
      making stomach cancer the leading cause of cancer death. The stomach cancer
      mortality rate of males was 1.9 times of that of females. The Chinese mortality
      rates of stomach cancer adjusted by the world population were 40.8 per 10(5) and
      18.6 per 10(5) of males and females, which were 4.2-7.9 (of males) and 3.8-8.0
      (of females) times of those in the developed countries. Age-adjusted mortality
      rates of stomach cancer in China have distinct geographical difference: form the
      lowest 2.5 per 10(5) to the highest 153.0 per 10(5) in the 263 surveyed
      localities, 15.3 per 10(5) in urban areas and 24.4 per 10(5) in rural areas
      giving a difference of 1.9 times. CONCLUSION: The prevention and treatment of
      stomach cancer in China, especially in the countryside and the under-developed
      areas in the northwest, should be a long-term focus in control of cancers of the
      digestive system. Urgent measures for prevention and early detection of stomach
      cancer should be taken.

PMID- 11977637
TI  - [Expression and hypoxic regulation of vascular endothelial growth factor and
      matrix metalloproteinase-9 in esophageal carcinoma].
AB  - OBJECTIVE: To investigate the the expression and hypoxic regulation of vascular
      endothelial growth factor(VEGF) and matrix metalloproteinase-9. METHODS: VEGF
      mRNA and MMP-9 mRNA were examined by reverse transcription-polymerase chain
      reaction (RT-PCR) in 43 esophageal carcinoma specimens including 18 para-tumorous
      esophageal tissues. The expression of VEGF protein and mean microvessel density
      (MVD) in 56 specimens were examined by immunohistochemical stain. The effect of
      hypoxia on VEGF and MMP-9 expression in esophageal cancer cell lines was
      quantitatively determined by enzyme linked immunosorbent assay (ELISA). RESULTS:
      The VEGF expression in the tumorous tissue, being significantly correlated with
      MVD in the tumor, was remarkably higher than that in the para-tumorous tissue.
      VEGF and MVD expression in the tumor was significantly associated with stage and
      metastasis of esophageal carcinoma. The MMP-9 expression in the tumorous tissue,
      being uncorrelated with vessel count and clinicopathologic features in esophageal
      carcinoma, was significantly higher than that in the para-tumorous tissue.
      Hypoxia significantly increased the VEGF expression in esophageal cancer cell
      lines but did not affect the MMP-9 expression. CONCLUSIONS: The expression of
      VEGF plays an important role in the angiogenesis and metastasis of esophageal
      cancer, which is regulated by hypoxia. VEGF may serve as a predictor of
      progression in esophageal carcinoma and a potential target for antiangiogenic
      therapy of esophageal carcinoma.

PMID- 11977639
TI  - [Malignant tumor and hyperfibrinogenemia].
AB  - OBJECTIVE: To investigate the blood fibrinogen (FIB) content before and after
      chemotherapy or radiotherapy in 43 malignant tumor patients. METHODS: COULTER ACL
      200 automated coagulation analyzer was used in monitoring FIB in the patients.
      RESULTS: The FIB content was significantly higher in malignant tumor patients
      than that in benign disease patients. Significant reduction was observed after
      treatment which became elevated again when there was recurrence or metastasis.
      CONCLUSION: Assessment of FIB not only helps to diagnose cancers but evaluate the
      therapeutic effect and prognosis also.

PMID- 11977638
TI  - [Amifostin in protection of kidney from cisplatinum injury].
AB  - OBJECTIVE: To evaluate Amifostin's effect on protecting kidney from cisplatinum
      (DDP) injury and its adverse reactions and safety. METHODS: 193 Patients were
      divided into two groups randomly: 102 in group A (treatment group) and 91 in
      group B (control group). Indexes such as blood routine, blood calcium, liver
      function, blood urea nitrogen (BUN), cretinine (C), and urinary N-acetyl-beta-D
      glucosaminidase (NAG)/C and micro-albumin (MAB/C) were monitored at different
      intervals before or after treatment. RESULTS: In the two courses of treatment in
      both groups, the deviation (D) values of MAB/C before treatment and on D2 in
      group A were lower than those in grop B (P < 0.05), so were those before
      treatment and on D4, D6, D10 and D14 (P < 0.01). The D-values of NAG/C before
      treatment and on D4, D6, D10 and D14 in the first course of group A were
      obviously lower than those on the corresponding days in group B (P < 0.01), so
      were those before treatment and on D2, D4, D6, D10 and D14 in the second course
      (P < 0.01). CONCLUSION: The reduction of MAB/C and NAG/C by Amifostin in group A
      demonstrates that: Amifostin is able to effectively protect the renal function,
      regardless of the type of tumor. In contrast with group B, Amifostin in group A
      shows no protection for tumor in lung cancer and ovarian cancer. The main side
      effects of Amifostin are mild hypotension, nausea, vomiting and hypocalcemia in
      some patients.

PMID- 11977640
TI  - [Feasibility of University of Washington-Quality of Life questionnaire for follow
      up of laryngeal cancer in China].
AB  - OBJECTIVE: To assess the feasibility of University of Washington Quality of Life
      (UW-QOL) questionnaire in laryngeal cancer patients treated by total or partial
      laryngectomy and their prognostic factors in China. METHODS: With UW-QOL
      questionnaire, a survey was conducted in patients treated by partial (81, Group
      A) or total (37, Group B) laryngectomy for laryngeal cancer. RESULTS: The
      composite QOL scores of group A (692.34 +/- 127.94) were higher than those of
      group B (636.35 +/- 139.97), with a difference statistically significant (P <
      0.05). Group A (74.32 +/- 23.82; 80.86 +/- 20.26) was better than group B (40.27
      +/- 25.76; 69.59 +/- 27.09) in speech and appearance (P < 0.001; P < 0.05); but
      group B (92.57 +/- 13.00) was superior to group A (83.02 +/- 20.47) in pain (P <
      0.01). Six factors including stage, operative, modality, complication,
      postoperative radiotherapy or chemotherapy, with whom to live, chronic disease
      before or after operation were related to postlaryngectomy QOL. CONCLUSION:
      Partial laryngectomy is superior to total laryngectomy in speech, appearance and
      overall QOL. UW-QOL questionnaire is suitable for QOL research in laryngeal
      cancer in China.

PMID- 11977641
TI  - [Surgical management of supraglottic laryngeal carcinoma in 182 patients with
      special emphasis on functional preservation].
AB  - OBJECTIVE: To explore the surgical methods and evaluate the long-term result of
      laryngectomy in patients with supraglottic laryngeal cancer. METHODS: 182
      patients with supraglottic laryngeal carcinoma underwent operation from 1979 to
      1999, with stage I 11, stage II 45, stage III 49 and stage IV 77 lesions. The
      choice of surgical procedure was decided with the disease condition of the
      larynx. The surgical procedures proposed by TD Wang were adhered to as: minor
      partial laryngectomy 36, major partial laryngectomy 85, subtotal partial
      laryngectomy with laryngoplasty 22 and total laryngectomy 39. RESULTS: The
      ultimate rate of larynx preservation was 78.6% (143/182) with 69.8% (88/126) in
      stage III and IV diseases. The decannulation rate was 81.8% in cases with
      preservation of laryngeal function. The overall 3- and 5-year survival rates were
      82.9% and 67.3%, with 76.88% and 57.4% in the advanced (stage III and IV) cases
      who survived with preserved laryngeal function. They were 82.5% and 67.0% in
      similar advanced cases who were treated by total laryngectomy. The difference in
      the survival rates between these two groups was not statistically significant.
      CONCLUSION: It is suggested that preservation of the laryngeal function be
      possible for advanced supraglottic laryngeal carcinoma without compromising the
      remote survival rate. To improve the rate of larynx preservation, one should
      follow the surgical methods suggested.

PMID- 11977642
TI  - [Management of perioperative respiratory problems in patients with tumor of
      trachea or carina].
AB  - OBJECTIVE: To summarise and analyse the experience and methods of managing the
      perioperative respiratory problems in patients with tumor of trachea or carina
      surgically treated during the last decade, and the ways of preventing severe
      postoperative respiratory complications in the future. METHODS: Thirty-eight
      patients with tumor of trachea or carina surgically treated from 1991 to 2000 by
      different modes of tracheobronchial plastic surgery were retrospectively studied
      to summarise and analyse the changes in preoperative pulmonary function,
      postoperative complications and the management of perioperative respiratory
      problems. RESULTS: Out of 38 patients, 29 (76.3%) gave abnormal results to
      preoperative pulmonary function tests. 55.3% (21/38) of the whole series
      developed 45 postoperative complications with respiratory complications as the
      major one (80.0%). Seventeen patients who had undergone carinal pneumonectomy or
      carinal resection plus reconstruction gave far more complications (28
      complications) than the remaining 21 patients treated by other modes of surgery
      (17 complications). Four patients died of postoperative complications with a
      mortality rate of 10.5%. CONCLUSION: Patients treated with carinal pneumonectomy
      or carinal resection plus reconstruction give much more complications than
      patients treated by any other modes of large airway surgery. Fiberoptic
      bronchoscopic (FOB) guided intubation, precise surgical treatment, postoperative
      mechanical ventilation support, use of effective antibiotics and sufficient
      nutritional support are important for a successful management of these patients.

PMID- 11977643
TI  - [Curative effect of percutaneous microwave coagulation therapy for hepatocellular
      carcinoma].
AB  - OBJECTIVE: To observe the curative effect of percutaneous microwave coagulation
      therapy (PMCT) with 2450 MHz microwave antenna for hepatocellular carcinoma.
      METHODS: Under local or epidural anesthesia, a thin percutaneous microwave
      antenna was introduced with ultrasound guidance into the tumor in the liver for
      thermo-coagulation. RESULTS: Among the 97 hepatic cancer lesions in 52 patients,
      61(62.9%) with phi < 3 cm were coagulated once. In follow-up of 6-12 months of
      these lesions, 57(93.4%) showed no recurrence by CT or MRI. Thirty-six (37.1%)
      with 3 cm < phi < 5 cm coagulated twice showed that 27 (75.0%) gave CR and 9
      (25.0%) gave PR by CT or MRI in follow up of 6 months. There were no serious
      clinical side effects or complications in the PMCT patients. CONCLUSION:
      Percutaneous microwave coagulation therapy gives good curative effect on liver
      tumor with phi < 3 cm. It is partly effective on lesions 3 cm < phi < 5 cm.

PMID- 11977644
TI  - [Postmastectomy radiotherapy for early breast cancer].
AB  - OBJECTIVE: To investigate the value of postmastectomy radiotherapy for early
      breast cancer. METHODS: From 1983 to 1991, 605 patients with T1-2N0-1M0 breast
      cancer were treated by radical mastectomy in our hospital. 149 patients underwent
      surgery alone(S group), and the remaining 456 patients received further adjuvant
      treatment. Of these patients, 135 received postoperative radiotherapy(S + R
      group), 113 adjuvant chemotherapy or tamoxifen(S + Y group), and 208 adjuvant
      chemotherapy or tamoxifen plus radiotherapy(S + Y + R group). Here, chemotherapy
      plus tomoxifen is designated as systematically therapy. The locoregional
      recurrence (LRR), disease-free survival (DFS), and overall survival (OS) rates
      were calculated by Kaplan-Meier analysis. The differences in locoregional
      recurrence and survival between these groups were compared by logrank test.
      RESULTS: The 10-year actuarial LRR, OS and DFS rates for all patients were 13.4%,
      81.6%, and 67.6%, respectively. The 10-year LRR rate was 10.3% for patients with
      negative axillary nodes, 9.4% for those with 1-3 positive nodes, and 25.9% for
      those with four or more positive nodes. The locoregional recurrence was
      significantly higher in patients with four or more positive nodes as compared to
      those with negative or 1-3 positive nodes (P < 0.05). For the S and S + R groups,
      the 10-year actuarial LRR rate was 18.7% in the S group and 7.5% in the S + R
      group (P = 0.017), the corresponding OS and DFS rates of these two groups were
      82.1% and 81.1% (P = 0.618), and 65.2% and 71.6% (P = 0.457), respectively. For
      the S + Y and S + Y + R groups, the 10-year actuarial LRR rate was 21.1% in the S
      + Y group and 9.5% in the S + Y + R group (P = 0.001), There, the corresponding
      OS and DFS rates were 75.5% and 85.0% (P = 0.020), and 59.3% and 70.2% (P =
      0.003), respectively. Only for patients with four or more positive nodes who had
      had systematic therapy, radiotherapy was beneficial; the 10-year actuarial LRR of
      patients who received systematic therapy only was 40.1% as compared with 15.1% of
      those who received systematic therapy plus radiotherapy; Their OS rates were
      55.4% and 67.1% (P = 0.040) and their DFS rates were 30.5% and 57.3% (P = 0.001).
      CONCLUSION: Post-mastectomy radiotherapy is able to significantly decrease the
      locoregional recurrence and improve the survival of patients with four or more
      positive axillary nodes. We suggest that postmastectomy radiotherapy be given as
      routine for these patients.

PMID- 11977645
TI  - [Capecitabine (xeloda) in the treatment of relapsed and metastatic breast
      cancer].
AB  - OBJECTIVE: To evaluate the response rate and adverse reactions of xeloda, an
      analogue of 5-fluorouracil, in the treatment of relapsed and metastatic breast
      cancer. METHODS: Twenty-two breast cancer patients who had recurrent and
      metastatic measurable foci were treated from Dec. 1999 to Feb. 2000. Xeloda was
      given, as a single drug, at a dose of or 2,510 mg/m2/d, bid, for two weeks
      followed by one week rest as one cycle, at least for one cycle in each patient.
      RESULTS: Among these 22 patients, there was no complete response. Rates of
      partial response 8(36.4%), stable disease 10(45.5%), progressive disease
      4(18.2%), and clinical benefit response (CR + PR + SD) 18(81.8%). The response
      rate in patients who had failed in previous chemotherapy of taxanes and/or
      anthracycline was 30.0%-33.3%. The common adverse reactions were hand-foot
      syndrome, skin pigmentation, nausea, vomiting, anorexia and fatigue. Mild
      moderate anemia and leukopenia were observed in 36.4% of patients. Stomatitis,
      dizziness, diarrhea and chest distress were present in some. One patient
      developed degree IV myelosuppression. Total bilirubin and alanine transaminase
      (ALAT) mild elevation occurred in a few patients. CONCLUSION: Xeloda is an
      effective drug in the treatment of patients with relapsed and metastatic breast
      cancer, especially for those who have failed in chemotherapy with taxanes and/or
      anthracycline. Xeloda is well tolerated but has mild adverse reactions.

PMID- 11977646
TI  - [The diagnostic value of mediastinoscopy and its application in staging for lung
      cancer].
AB  - OBJECTIVE: To evaluate the value of mediastinoscopy in diagnosing unknown
      mediastinal disease and staging of lung cancers. METHODS: From October 2000 to
      August 2001, 41 patients were examined by cervical mediastinoscopy with or
      without anterior mediastinotomy for diagnostic and staging purposes. Of these 41
      patients, 12 were for diagnosis of unknown mediastinal disease, 3 for diagnosis
      and staging of pulmonary nodule or mass clinically suspected to be malignancy and
      26 for the staging of lung cancer. RESULTS: Ten of 12 patients with unknown
      mediastinal disease were diagnosed pathologically as thymoma in 1, metastatic
      lesion from lung cancer in 1, metastatic thyroid carcinoma in 1, lymph node
      hyperplasia in 1, teratoma in 1, sarcoidosis in 1, inflammatory pseudotumor in 1
      and tuberculosis in 3, giving a diagnostic rate of 83.3%. Of three patients with
      suspected malignancy, one was diagnosed as tuberculosis by cervical
      mediastinoscopy and the other two as lymphoma and pulmonary inflammatory
      pseudotumor by thoracoscopy and thoracotomy. The sensitivity and specificity of
      mediastinoscopy for the staging of mediastinal nodes in 26 lung cancers were
      87.5% and 100%. Only one wound infection but no other major complication was
      found. CONCLUSION: Mediastinoscopy is a safe procedure which can accurately
      provide information on diagnosis and staging.

PMID- 11977647
TI  - [Tumor downstaging through preoperative chemoradiotherapy in locally advanced
      rectal cancer].
AB  - OBJECTIVE: To evaluate the impact of preoperative chemoradiotherapy on patients
      with locally advanced rectal cancer by clinical and pathological characteristics.
      METHODS: From July 1994 to May 1995, 36 patients with locally advanced rectal
      cancer were treated. Pathology: adenocarcinoma 27, mucinous adenocarcinoma 7 and
      ductal adenocarcinoma 6. The protocol was carried out in sequence of chemo-
      >radio-->surgery-->chemotherapy. The treatment began with preoperative
      chemotherapy with folinic acid 50 mg followed by 5-FU bolus of 300 mg/m2 given
      for two cycles on d1-5 and d22-26 before irradiation. Radiation therapy was
      delivered to a dose of 45 Gy, 1.8 Gy per fraction, 5 days a week. Surgery was
      done 4-6 weeks after this preoperative treatments. Another 2 to 4 cycles of
      chemotherapy were added 2 to 4 weeks after operation. Twenty-one patients were
      treated by Dixon's operation, 14 patients by Mile's operation and 1 by local
      tumorectomy through the rectum. Radical operation was performed in 29 patients
      and palliative resection was done in 7 patients. RESULTS: Grade III hematological
      toxicity was observed in only 2(5.6%) patients. No patient had grade III or IV
      acute toxicity in the gastrointestinal, skin or urological systems. All patients
      underwent surgery. The perioperative morbidity rate was 13.8% with no mortality
      or late toxicity. As a result of this preoperative management, the tumor was
      reduced by an average of 28.0%, with a complete pathological response in 4(11.1%)
      patients. In 28 CR + PR (77.8%) patients, a downstaging in 19(52.8%) patients was
      observed. Sixty percent of positive lymph nodes as assessed by transrectal
      ultrasonography before therapy became pathologically negative postoperatively,
      with the frequency of lymph node metastasis decreased by 46.0%(83.0% to 37.0%).
      CONCLUSION: Preoperative radiochemotherapy is proved as a safe method with a
      tolerable toxicity. Complete pathological response, shrinkage of the primary
      tumor and decrease in lymph node metastasis are observed after preoperative
      radiochemotherapeutic regimen. An overall benefit of downstaging the primary
      tumor and a greatly enhanced effect of surgery is enjoyed by the patients.

PMID- 11977648
TI  - [Late course accelerated hyper-fractionated radiotherapy of upper and middle
      thoracic esophageal T2N0M0 carcinoma].
AB  - OBJECTIVE: To analyse the result of late course accelerated hyper-fractionated
      radiotherapy (LCAHFR) of upper and middle thoracic segment esophageal T2N0M0
      carcinoma. METHODS: Fifty-three patients with squamous cell esophageal T2N0M0
      carcinoma in the upper and middle segment were treated by LCAHFR from August 1994
      to January 2000. The design of the radiation fields were based on CT and barium
      examination. All patients were treated with the conventional fractionated
      radiotherapy during the first two-thirds of the treatment to a dose about 41.4
      Gy/23 F/4 to 5 weeks. This was followed by accelerated hyper-fractionated
      irradiation using reduced fields, twice daily at 1.5 Gy per fraction to a dose
      about 27 Gy/18 d. Thus, the total dose was 67-70 Gy/40-43 F/40-49 d. RESULTS: The
      1-, 2- and 5-year actuarial survival rates were 89.9%, 66.8% and 51.2%,
      respectively. The 1-, 2- and 5-year local control rates were 92.1%, 87.1% and
      87.1%. Of the 17 patients who died, 5 died of local failure (29.4%), 9 (52.9%) of
      distant metastasis, 5 (29.4%) of lymph metastasis and 1 (5.9%) of bleeding from
      the esophagus. The Cox multivariate model showed that the site of lesion was the
      only prognostic factor, with upper better than the middle segment. CONCLUSION:
      Late course accelerated hyper fractionated radiotherapy is one of the best
      radiation treatment regimen for early esophageal carcinoma in the upper and
      middle thoracic segment.

PMID- 11977650
TI  - [Comparison of MR cholangiopancreatography and surgical diagnosis of extrahepatic
      bile duct carcinoma].
AB  - OBJECTIVE: This work was done to compare the validity of various imaging methods,
      e.g. ultrasonography (US), computed tomography (CT), endoscopic retrograde
      cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTC),
      and, especially, magnetic resonance cholangiopancreatography (MRCP) for
      extrahepatic bile duct carcinoma. METHODS: Sixty-five such patients who were
      operated and confirmed by pathology were used. Sixty patients had been examined
      by US; 52 by CT; 20 by ERCP; 9 by PTC and 20 by MRCP. The results of these
      imaging methods were compared with those of operative and pathological findings.
      RESULTS: The diagnostic accuracy rates of site location were US 81.7%, CT 84.6%,
      ERCP 75.0%, PTC 88.9% and MRCP 100%, respectively. The quality diagnostic
      accuracy rates were US 73.3%, CT 82.7%, ERCP 75.0%, PTC 88.9% and MRCP 95.0%,
      respectively. CONCLUSION: MRCP is superior to US, CT, ERCP and PTC not only in
      demonstrating the position but also the nature of extrahepatic bile duct
      carcinoma.

PMID- 11977649
TI  - [Effects on micro-vessel density after pre-operative intra-arterial infusion
      chemotherapy in colorectal cancer].
AB  - OBJECTIVE: To evaluate the effects of pre-operative intra-arterial infusion
      chemotherapy on colorectal cancer. METHODS: Twenty-eight patients with colorectal
      cancer, treated by surgery from February to October 2000, were divided into two
      groups randomly. There were 12 patients in group A (pre-operative intra-arterial
      infusion chemotherapy) and 16 in group B (control). Arterial contrast technique
      was used in group A, then mitromycin 10 mg, 5-Fu 1,000 mg, epirubicin 60 mg were
      given through Weidner's way. RESULTS: Micro-vessel density in the center, surface
      of the tumor and adjacent tissue around the tumor were 40.46 +/- 7.06, 52.27 +/-
      18.40, 49.92 +/- 8.15 in group A, and 46.09 +/- 12.21, 73.44 +/- 22.06, 51.94 +/-
      12.64 in group B. Micro-vessel density on the surface in group A was
      significantly lower than that of group B (P < 0.05), with no significance between
      the center and the adjacent tissue. CONCLUSION: Pre-operative intra-arterial
      infusion chemotherapy is able to reduce micro-vessel density on the surface of
      colorectal tumor.

PMID- 11977652
TI  - [Tumor of the skull-report on 119 patients].
AB  - OBJECTIVE: To study the pathologic type, clinical manifestations and treatment of
      skull neoplasms. METHODS: A series of 119 patients with skull neoplasm were
      analyzed retrospectively with respect of clinical manifestations, radiologic
      features, treatment and prognosis. RESULTS: 122 operations were done with 3
      patients being operated twice. Complete resection was done 75 times, subtotal
      resection 24 times, partial resection 22 times and biopsy only once. Gross type:
      exophytic 43(36.1%), endophytic 27(22.7%) and mixed type 49 (41.2%). Among the 85
      patients followed, 78.6% have recovered and are living well, 16.6% of patients
      are self-caring, 2 need others' help and 2 have died. CONCLUSION: Most skull
      neoplasms require neurosurgical intervention. Surgical excision is able to
      confirm the diagnosis, slow down the progression of neurologic dysfunction,
      prolong the patients' lives and improve the cosmetic results.

PMID- 11977651
TI  - [Matrix metalloproteinase 9 expression is induced by Epstein-Barr virus LMP1 via
      NF-kappa B or AP-1 signaling pathway in nasopharyngeal carcinoma cells].
AB  - OBJECTIVE: To clarify if Epstein-Barr virus encoded LMP1 induces matrix
      metalloproteinase 9 expression via NF-kappa B or AP-1 signaling pathway, which
      gives evidence to the elucidation of the mechanism of LMP1- mediated
      carcinogenesis. METHODS: To determine whether LMP1 or its mutants contribute to
      MMP9 production via NF-kappa B or AP-1 transcription factor, MMP9-chloramphenicol
      acetyl transferase (CAT), NF-kappa B mut 9-CAT, AP-1 mut MMP9-CAT were
      transfected into human nasopharyngeal carcinoma cells stably expressing LMP1
      (HNE2-LMP1) or its mutants, [HNE2-LMP1 (1-185), HNE2-LMP1 (1-231), HNE2-LMP1
      delta 187-351] by electroporation technic. The difference of MMP9 reporter
      activity among those cell lines was detected by CAT assay and expression of MMP9
      was determined in nasopharyngeal carcinoma cells stably expressing LMP1 or its
      mutants by zymographic analysis. In the meantime, efforts were made to
      demonstrate if LMP1 regulates NF-kappa B or AP-1 activation using reporter gene
      analysis. RESULTS: In contrast with vector-transfected cells, MMP9 CAT activity
      in HNE2-LMP1, HNE2-LMP1 (1-185), HNE2-LMP1(1-231), HNE2-LMP1 delta 187-351
      increased 7.2, 1.3, 3.3, 4.0 times respectively. Zymographic analysis
      demonstrated that the 92 kDa MMP9 expression was induced in HNE2-LMP1, HNE2
      LMP1(1-231) and HNE2-LMP1 delta 187-351 cells, whereas it was negative in HNE2
      pSG5 and HNE2-LMP1 (1-185) cells. As compared to the HNE2 cells, NF-kappa B or AP
      1 reporter activity in HNE2-LMP1 cells were increased 13.8, 8.4 fold
      respectively. Moreover, In contrast with MMP9 CAT-transfected cells, MMP9 CAT
      activity in NF-kappa B mut MMP9-CAT or AP-1 mut MMP9-CAT transfected HNE2-LMP1,
      HNE2-LMP1 (1-185), HNE2-LMP1(1-231) and HNE2-LMP1 delta 187-351 cells were
      significantly decreased by 18.1% or 16.3%, 35.0% or 33.3%, 29.1% or 26.1% from
      the original level. However, there was no difference in NF-kappa B mut MMP9-CAT
      or AP-1 mut MMP9-CAT transfected HNE2-pSG5, HNE2-LMP1 (1-185) cells. CONCLUSION:
      In nasophargyngeal carcinoma, Epstein-Barr virus-encoded LMP1 induces MMP9
      transcription and enzymatic activity via an NF-kappa B or AP-1 signaling pathway,
      which may contribute to invasiveness and metastasis.

PMID- 11977653
TI  - [Combined high dose leucovorin and 5-fluorouracil continuous infusion for head
      neck and digestive tract cancers].
AB  - OBJECTIVE: To evaluate the feasibility of combined high dose leucovorin plus 5
      fluorouracil infusion for head-neck and digestive tract cancers. METHODS: Fifty
      six patients with head-neck and digestive tract cancer were treated by combined
      high dose leucovorin (HD-CF) plus 5-fluorouracil (5-Fu) 48 hour continuous
      infusion with each patient receiving an average of 3.8 cycles (2-6 cycles).
      Twenty-five of these 56 patients were untreated and 31 recurrent. Their clinical
      stages were II 4, III 13 and IV 39. RESULTS: The over all response rate (CR + PR)
      was 35.7% and the clinical beneficial response rate was 80.4%. The main side
      effects were peripheral phlebitis, suppression of bone marrow, oral ulcer, nausea
      and vomiting of grade I to II. CONCLUSION: High dose leucovorin plus 5
      fluorouracil 48 hour continuous infusion is useful with favorable cost/utility
      ratio for head-neck and digestive tract cancer patients. Further studies are
      warranted.

PMID- 11977654
TI  - Time to deliver 'free' care.

PMID- 11977655
TI  - Dealing with diabetes.

PMID- 11977656
TI  - Special interest.

PMID- 11977657
TI  - Stagnating profession.

PMID- 11977658
TI  - Two of a kind.

PMID- 11977659
TI  - Do you have what it takes?.

PMID- 11977660
TI  - My defining moment.

PMID- 11977661
TI  - Binding solution.

PMID- 11977663
TI  - Rapid access for patients with head and neck lumps.
AB  - BACKGROUND: In the White Paper The New NHS: Modern, Dependable (DoH 1997), the
      government states that anyone with suspected cancer will be able to be seen by a
      specialist within two weeks of referral by a GP. Staff at Southport General
      Infirmary set up a rapid access clinic for patients referred with a neck lump to
      meet these targets. A protocol was devised to deal with these new patients and
      the clinic was audited during the first six months to ensure that the two-week
      target was being met. CONCLUSION: The results of the audit showed that the rapid
      access clinic was able to provide a fast, quality service for this small number
      (n = 58) of patients. The majority (n = 49) (84 per cent) of patients were seen
      within the target time. The remaining patients were not seen within the two-week
      target because of delays in receiving GP referrals and patients' difficulties in
      meeting the allocated appointment.

PMID- 11977664
TI  - Young people's pathway to smoking cessation.
AB  - In preparing a young people's smoking cessation service in Sheffield, the author
      carried out a literature search and organised focus groups with young people to
      establish their specific problems with stopping smoking. This article discusses
      her findings and identifies the possible needs of young people who want support
      and advice when giving up smoking.

PMID- 11977667
TI  - Motivating change.
AB  - Effective health behaviour change consultations demand a high level of skill and
      well-practised strategies used in a patient-centred way of working.

PMID- 11977668
TI  - Working together.

PMID- 11977671
TI  - Breath of life.

PMID- 11977676
TI  - Party lines.

PMID- 11977675
TI  - Stepping up to first base. Interview by Graham Scott.

PMID- 11977677
TI  - A turning point.

PMID- 11977678
TI  - A lesson for us all. Interview by Ruth Williams.

PMID- 11977679
TI  - Statin safety.

PMID- 11977680
TI  - An appetite for life.

PMID- 11977681
TI  - Who owns our future?

PMID- 11977684
TI  - Wound cleansing: ritualistic or research-based practice?
AB  - Wound cleansing is an important component of wound management. When carried out
      correctly it can improve healing, but when undertaken unnecessarily it can impede
      wound progress. Literature suggests that nurses continue to rely on ritualistic
      practice rather than using research or best evidence to inform patient care. The
      rationale and implications for wound cleansing are examined in relation to
      cleansing solutions, technique and equipment.

PMID- 11977685
TI  - Possible influences on clinical supervision.
AB  - This article discusses clinical supervision and suggests that, aside from helping
      nurses to enhance their clinical effectiveness, it could offer experiential
      methods of assisting nurses to identify and locate supportive networks in the
      workplace. The advantages and difficulties of supervision relationships are
      described in context, including some consideration of authority and control.

PMID- 11977687
TI  - Reducing the risk of healthcare-acquired infection.
AB  - Many patients experience increased hospital stays, poor health outcomes, or die
      each year, as a result of healthcare-acquired infections. Evonne Curran discusses
      the most common types of infection and suggests how nurses can minimise the risks
      of infection in clinical settings.

PMID- 11977692
TI  - Walk this way.

PMID- 11977693
TI  - Letter from America.

PMID- 11977694
TI  - United we stand.

PMID- 11977695
TI  - A select few.

PMID- 11977696
TI  - Is it or isn't it?.

PMID- 11977700
TI  - Information needs of patients with cancer.
AB  - AIM: To establish the amount of information patients were given at their initial
      diagnosis of cancer, what information was beneficial and if there were any
      individual factors that made patients have different information needs. METHOD:
      Ten recently diagnosed patients were interviewed using a structured format to
      establish their understanding of the information given at the time of diagnosis.
      RESULTS: Patients who suspected their diagnosis or who had been prepared were
      able to understand and retain this information. In contrast, those who did not
      suspect or who had not been prepared in any way were unable to take in the
      information initially. CONCLUSION: The patient's level of preparation should be
      established by the healthcare professional before the diagnosis is given.

PMID- 11977701
TI  - An evaluation of staff nurse role transition.
AB  - This article summarises a study undertaken to examine the factors that influence
      role transition from student to staff nurse. It considers the impact of Project
      2000 and reports on issues that enhance or inhibit role transition for newly
      qualified nurses. The study supports the UKCC's findings that students are able
      to question and evaluate practice, but do not feel they have the necessary
      clinical skills on qualifying. The evaluation showed that structured support is
      vital to assist role transition and can reduce anxiety and culture shock even in
      very busy areas. The participants identified that the newly acquired
      responsibility and accountability can be both enjoyable and threatening.

PMID- 11977704
TI  - Carotid endarterectomy.
AB  - Cerebrovascular accident or stroke is a common cause of death and disability.
      Carotid endarterectomy is a surgical procedure performed to prevent ischaemic
      stroke. This article provides an overview of atherosclerotic carotid disease and
      issues involved with carotid endarterectomy.

PMID- 11977703
TI  - Prevention of pneumococcal disease in young children.
AB  - Increasing pneumococcal resistance to antimicrobial drugs, and the rapid spread
      of resistant strains throughout the world, underlines the importance of
      vaccination. Although traditional polysaccharide pneumococcal vaccines have been
      in use since the 1980s, and are effective among certain age groups, they do not
      provide protection to children under the age of two years who are at highest risk
      of infection from pneumococcal disease. The new conjugate vaccine is expected to
      contribute to a decreased need for antibiotic treatment, fewer GP visits and
      reduced hospitalisation rates.

PMID- 11977713
TI  - Children in need.

PMID- 11977714
TI  - Get on the skills escalator.

PMID- 11977715
TI  - Group dynamics.

PMID- 11977716
TI  - Students on course.

PMID- 11977718
TI  - Hidden agenda.

PMID- 11977719
TI  - Recipe for change.

PMID- 11977720
TI  - Back to life.

PMID- 11977722
TI  - Career pathways in research: support and management.
AB  - This article, the third in the series on career pathways, highlights support and
      management careers open to nurses working in the NHS and research and
      development, or people working for funding bodies or charitable organisations.
      These roles involve ensuring that the right infrastructure is in place to support
      research projects, and the correct decisions are made about which research
      projects should be supported and commissioned.

PMID- 11977723
TI  - Understanding and dealing with anger, aggression and violence.
AB  - Following the launch in 1999 of the government's Zero Tolerance campaign against
      violence and aggression towards healthcare staff, Phil Garnham looks at how
      healthcare staff can help to prevent violence and aggression by understanding
      patient issues, and find a safe, productive solution together.

PMID- 11977724
TI  - The Tissue Viability Society.

PMID- 11977725
TI  - An unusual case of tissue breakdown secondary to TB.
AB  - Despite the many advances in technology, research and educational initiatives in
      tissue viability, wound management remains a complex and challenging area for
      healthcare professionals. This article describes the management of an unusual
      groin wound that developed as a result of tissue breakdown secondary to
      tuberculosis.

PMID- 11977726
TI  - Use of compression hosiery in venous leg ulceration.
AB  - Venous leg ulceration is a common problem in older people that adversely affects
      their quality of life. It is also a major cause of morbidity for many patients in
      hospital and community settings. Patients experience considerable pain and
      distress as a result of this condition and annual costs to the NHS are high.
      However, good nursing management and the correct use of compression therapy can
      lead to faster healing rates (Effective Health Care 1997), and reduced nursing
      time. This article discusses the use of compression hosiery in the prevention and
      treatment of venous leg ulcers.

PMID- 11977729
TI  - Improving pressure ulcer prevention through education.
AB  - Pressure ulcers adversely affect the quality of life of many patients and cause
      anxiety and distress for their families. Pressure ulcer prevention and management
      is an integral part of nursing practice, but despite numerous policies and
      guidelines, research, and improvements in equipment, the incidence and prevalence
      of pressure ulcers have not fallen. In this article, the author examines issues
      involved in promoting more effective pressure ulcer management.

PMID- 11977731
TI  - Management of a diabetic foot ulcer using larval therapy.
AB  - Diabetic foot ulcers should be treated to maintain health status, improve quality
      of life, reduce the number of amputations and lower costs. Many centres that
      treat diabetic foot ulcers use a multidisciplinary team approach, which comprises
      medical staff, nurses, podiatrists and an orthotist. At the Manchester Diabetes
      Centre, larval therapy has been used for several years to debride sloughy
      diabetic foot ulcers. This case history demonstrates the adverse effects of
      diabetes on feet, and the multidisciplinary team's contribution to successful
      treatment and healing of a complex foot lesion.

PMID- 11977734
TI  - [23rd annual meeting of Japanese Society for Clinical Toxicology symposium-
      development of treatment for acute poisoning in the 21st century].

PMID- 11977735
TI  - [23rd annual meeting of Japanese Society for Clinical Toxicology panel discussion
      - the present situation on analysis of chemicals in emergency centers following
      distribution of analytical equipment].

PMID- 11977736
TI  - [Analysis of MDMA and PCP by GC-MS from patients admitted to the critical care
      medical center].
AB  - In our country, abuse of methamphetamine has increased. Furthermore, dealings of
      other drugs by using internet have increased. But, the poison cases of 3,4
      methylenedioxymethamphetamine (MDMA) and phencyclidine (PCP) have never been
      reported in our country. We report an MDMA poison case and a PCP poison case. We
      could detect MDMA, MDA or PCP by GC-MS from urine and serum of patients admitted
      to the critical care medical center of Nippon Medical School. Case 1: A 23-year
      old foreign female was admitted to our hospital because of disturbance of
      consciousness. Her friend said that she had been found lying on the floor of the
      bathroom after taking a tablet. The screening test by Triage showed AMP positive.
      Not methamphetamine but MDMA and MDA were detected from urine and serum of the
      patient by GC-MS. Case 2: A 27-year-old foreign female was admitted to our
      hospital because of restlessness and excitement. Her friend said that she had
      become restless and excited after taking 15-30 tablets of Tylenol. The screening
      by Triage showed BZO and PCP positive. Not acetaminophen but PCP was detected in
      the patient's sample by GC-MS. Drug abuse has expanded to Japan over the border.
      New responses to abuse drugs with respect to medical treatment and drug analyses
      should be established.

PMID- 11977737
TI  - [A case of fluvoxamine overdose].
AB  - Selective serotonin reuptake inhibitors (SSRI) are newly developed
      antidepressants authorized in 1999 in Japan. We experienced a case of drug
      poisoning including fluvoxamine, one of SSRI. A comatose nineteen-year-old girl
      was transported to our ER in the morning on July 25, 2000. There remained many
      empty packages of fluvoxamine and several sorts of tranquilizers in the room. Her
      consciousness became alert over the next morning. HPLC analysis revealed
      fluvoxamine, chlorpromazine, promethazine, biperiden, phenobarbital, and
      zopiclone in her blood and that serum concentrations of the first three were
      above the therapeutic ranges. The peak values of fluvoxamine, chlorpromazine, and
      promethazine were 1,343 ng/ml (6.7 times of the upper limit), 861 ng/ml (2
      times), and 529 ng/ml (1.3 times), respectively. Fluvoxamine must be a main cause
      of her toxic symptoms although other CNS-depressing drugs might work jointly.

PMID- 11977738
TI  - [On publication of the series "Practical Analysis of Toxic Substance Useful for
      Clinical Toxicology"].

PMID- 11977739
TI  - [Practical analysis of toxic substances useful for clinical toxicology-
      glufosinate].

PMID- 11977740
TI  - [Investigation of acute poisoning in household pets].

PMID- 11977741
TI  - [On organizing the 24th annual meeting of the Japanese Society for Clinical
      Toxicology].

PMID- 11977742
TI  - Medical malpractice insurance 2002.

PMID- 11977743
TI  - Restoring stability to the professional medical liability market.

PMID- 11977744
TI  - Medical Liability Task Force. Findings and recommendations.

PMID- 11977745
TI  - Professional liability insurance. I. A historical perspective.

PMID- 11977746
TI  - Professional liability insurance. II. The legal environment.

PMID- 11977747
TI  - Professional liability insurance. III. The clinical environment.

PMID- 11977748
TI  - Professional liability insurance. IV. Evaluating professional liability carriers.

PMID- 11977749
TI  - Professional liability insurance. V. The future of medicine.

PMID- 11977750
TI  - Medical professional liability insurance 2002. VI. Are we entering another
      crisis?

PMID- 11977751
TI  - A primer on medical economics. Chapter 5: math survival skills.

PMID- 11977752
TI  - [HIV-1 genetic diversity: mechanism and its biological implication].

PMID- 11977753
TI  - [Emergence of amantadine-resistant influenza A viruses].

PMID- 11977754
TI  - [Prion diseases in animals].

PMID- 11977755
TI  - [Current topics of prion disease].

PMID- 11977756
TI  - [Biosynthesis and conversion mechanism of prion protein].

PMID- 11977757
TI  - [Biochemistry of conformational transition and aggregation of amyloid proteins].

PMID- 11977758
TI  - [Molecular biology of yeast prions].

PMID- 11977759
TI  - [Mouse hepatitis virus (MHV) receptor and its interaction with MHV spike
      protein].

PMID- 11977760
TI  - [Structure and function of poliovirus receptor].

PMID- 11977761
TI  - [Receptor and molecular mechanism of the host range variation of influenza
      viruses].

PMID- 11977762
TI  - [The cellular receptor for measles virus].

PMID- 11977763
TI  - [Recognition of dsRNA by toll-like receptor 3].

PMID- 11977764
TI  - [Viral hemorrhagic fever and its diagnosis system in Japan].

PMID- 11977765
TI  - [The mechanism of MHV transcription].

PMID- 11977766
TI  - [From the first to the 50th annual meeting of the Japanese Society for Virology
      and my concern for a bio-terrorism using a smallpox virus as a weapon].

PMID- 11977767
TI  - Long-term effects of benidipine hydrochloride on severe left ventricular
      hypertrophy and collagen metabolism in patients with essential hypertension.
AB  - OBJECTIVES: The long-term effects of benidipine on left ventricular hypertrophy
      (LVH) and collagen metabolism were examined in patients with essential
      hypertension. METHODS: Forty patients with untreated essential hypertension were
      given benidipine at a dose of 6 mg a day. Routine echocardiographic parameters,
      serum concentrations of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor
      of metalloproteinase-1 (TIMP-1) were analyzed before and 12 months after
      treatment with benidipine. Patients were classified according to left ventricular
      mass index (LVMI) into three groups: severe LVH (LVMI > or = 159), mild LVH (159
      > LVMI > or = 125) and no LVH (LVMI < 125). RESULTS: Serum levels of free TIMP-1
      to MMP-1 ratio were significantly higher in patients with severe LVH than in the
      other two groups before treatment. There was a significant positive correlation
      between the free TIMP-1 to MMP-1 ratio and LVMI in all study subjects (r = 0.51,
      p < 0.01). Twelve months after treatment, percentage changes of the LVMI and free
      TIMP-1 to MMP-1 ratio were significantly larger in the patients with severe LVH (
      27% and -54%) than with mild LVH (-12% and -23%) or no LVH (-4% and -11%),
      respectively. Changes in the systolic blood pressure but not changes in the free
      TIMP-1 to MMP-1 ratio correlated with changes in the LVMI in patients with mild
      LVH (r = 0.78, p < 0.01). Changes in the free TIMP-1 to MMP-1 ratio but not
      changes in the systolic blood pressure correlated with changes in the LVMI in
      patients with severe LVH (r = 0.69, p < 0.01). CONCLUSIONS: Long-term
      administration of benidipine reduced left ventricular mass and normalized
      systemic collagen type I degradation abnormalities in essential hypertensive
      patients with severe but not mild LVH.

PMID- 11977768
TI  - [Prevalence and clinical background of exercise-induced ventricular tachycardia
      during exercise testing].
AB  - OBJECTIVES: This study assessed the prevalence and clinical background of
      exercise-induced ventricular tachycardia during exercise testing. METHODS:
      Complications during exercise testing were reviewed in 25,075 consecutive
      patients, 14,037 men and 11,038 women, who underwent a total of 47,656 maximal
      treadmill or bicycle exercise tests between April 1985 and March 1999. The mean
      age of the patients was 53.3 +/- 8.8 (mean +/- SD) years. Non-sustained
      ventricular tachycardia was defined as 8 or more consecutive ventricular ectopic
      beats at > 100 beats/min. A total of 126 patients undergoing exercise testing to
      evaluate the efficacy of pharmacotherapy for ventricular tachycardia were
      excluded. RESULTS: The major reasons for the exercise test were chest pain
      (27.0%) and screening (20.3%). Twenty patients (0.08%) had exercise-induced
      ventricular tachycardia. Six patients had ischemic heart disease, two had
      cardiomyopathy, five had other cardiac diseases, and seven patients showed no
      clinical evidence of heart disease. The incidence of ventricular tachycardia in
      patients with cardiomyopathy (2/109) was higher than in other patients, but the
      number of patients with ventricular tachycardia was small. Ventricular
      tachycardia was documented at heart rates of more than 80% of predicted maximal
      heart rate in 12 of the 20 patients. CONCLUSIONS: These results suggest that the
      exercise testing can be done safely when the end-point criteria are properly
      applied.

PMID- 11977769
TI  - [Hypertrophic cardiomyopathy with mid-ventricular obstruction complicated with
      apical left ventricular aneurysm and ventricular tachycardia: a case report].
AB  - A 69-year-old man was admitted with palpitations and syncope. His medical history
      included hypertension and left ventricular hypertrophy. Arterial pulsation was
      not palpable on admission. Electrocardiography revealed ventricular tachycardia,
      and cardioversion restored normal sinus rhythm. An electrophysiological study
      reproducibly induced polymorphic ventricular tachycardia, so a cardioverter
      defibrillator was implanted. Echocardiography revealed mid-ventricular
      obstruction and an apical aneurysm, and Doppler color flow imaging showed a
      diastolic paradoxic jet from the apex toward the base. Coronary angiography
      showed no stenosis of the extramural coronary arteries. Ventricular tachycardia
      on admission showed a right bundle branch block pattern and a superior axis
      deviation, so the arrhythmia was thought to originate from the apical aneurysm.
      Apical aneurysm can result from elevated intraventricular pressure or relative
      myocardial ischemia. This is a rare case of hypertrophic cardiomyopathy with mid
      ventricular obstruction complicated with apical aneurysm and polymorphic
      ventricular tachycardia.

PMID- 11977770
TI  - [Biventricular pacing using two pacemakers and triggered VVT mode in patients
      with atrial fibrillation and congestive heart failure: a case report].
AB  - A 76-year-old female had undergone implantation of a single chamber pacemaker for
      sick sinus syndrome 20 years previously. She developed chronic atrial
      fibrillation and required repeated admission due to congestive heart failure. She
      had significant mitral and tricuspid regurgitation. Paradoxical movement of the
      intraventricular septum was severe. Due to right ventricular apical pacing,
      significant interventricular conduction delay was present with a paced QRS
      duration of 189 msec. The left ventricular pacing lead was positioned via the
      coronary sinus. The mode of the previously implanted pacemaker was set at VVT.
      Biventricular pacing could be achieved even in intrinsic beats by VVT mode. The
      battery life time was improved. This method is useful in patients with
      conventional pacemakers.

PMID- 11977771
TI  - [Specialized tertiary care facilities for adults with congenital heart disease in
      North America and the United Kingdom: future directions in Japan].
AB  - Specialized tertiary care facilities have been established to care for the
      increasing numbers of adults with congenital heart disease. Because this
      cardiovascular subspecialty is relatively new, the dedicated facilities have
      evolved without preexisting guidelines. Therefore, a mini-review was conducted of
      specialized tertiary care facilities for adults with congenital heart disease in
      North America and the United Kingdom, to illuminate the future directions of
      continuous management of these patients in Japan. Specialized tertiary care was
      provided by integrated collaborative teams that involve medical and pediatric
      cardiologists, cardiac surgeons, and non-cardiac consultants. Continuing growth
      of this relatively new patient population and further evolution of specialized
      care facilities can be anticipated.

PMID- 11977772
TI  - A 68-year-old female with repetitive palpitation. Adrenal pheochromocytoma.

PMID- 11977773
TI  - [A young man with frequent ventricular tachycardia. Arrhythmogenic right
      ventricular cardiomyopathy].

PMID- 11977774
TI  - We need relief and reform now.

PMID- 11977775
TI  - Angelo S. Agro, MD.

PMID- 11977776
TI  - The Health Wellness Promotion Act and available CPT codes.

PMID- 11977777
TI  - The informed consent doctrine. A defined responsibility.

PMID- 11977778
TI  - Are we prepared for a smallpox attack?

PMID- 11977779
TI  - Hannibal Lecter: the honey in the lion's mouth.
AB  - This paper examines the psychopathology of Hannibal Lecter, the fictional killer
      and cannibal in Thomas Harris's trilogy: Red Dragon, Silence of the Lambs, and
      Hannibal from an object relations point of view. The victim of childhood trauma
      involving the killing of his family and the cannibalization of his baby sister,
      Lecter suffers from posttraumatic stress disorder. Using the theories of Melanie
      Klein, Harry Guntrip, D.W. Winnicott, M. Khan, as well as Otto Kernberg, this
      paper explores the reasons Lecter is compelled to kill and eat parts of some of
      his victims. He is locked in the paranoid-schizoid position, relies heavily on
      schizoid defenses, such as splitting and projective identification, but is unable
      to avoid psychotic breaks with reality to reenact his early traumas. Through his
      reunion with Clarice Starling, Lecter attempts the process of reparation and an
      entry into the depressive position.

PMID- 11977780
TI  - Fundamental dilemmas in contemporary psychotherapy: a transtheoretical concept.
AB  - The transtheoretical nature of fundamental dilemmas in contemporary psychotherapy
      is explored. The basic distinction between technical and ethical dilemmas in
      clinical practice is discussed, as well as the ramifications for the
      psychotherapist. Clinical dilemmas identified by survey research studies and
      interviews with master psychotherapists are reviewed. In addition to dilemmas
      relevant to circumscribed areas of psychotherapy, such as brief therapy, managed
      mental health care, sexual questions, feminist therapy, dilemmas fundamental to
      the psychotherapeutic process as a whole are examined. Finally, clinical examples
      are provided that include such issues as hospitalization of the suicidal patient,
      dealing with known contraindications, treating the intractable patient, and self
      care of the psychotherapist.

PMID- 11977781
TI  - Reflections on gifts in the therapeutic setting: the gift from patient to
      therapist.
AB  - Since Freud's time, psychoanalytically oriented therapists have been wary of
      accepting gifts from patients, although they have done so in some circumstances
      within the sanctum of their offices. After providing a working definition of the
      word "gift" for the purposes of this clinical discussion, the article reviews the
      relevant literature on the subject. The author presents clinical material in
      which he describes how gifts were presented by patients within the context of
      their treatment processes. The article concludes with the author's attempt to
      define some of the variables that affect the response of the therapist to a
      patient's gift, and expounds on those variables in terms of their influence on
      technique.

PMID- 11977782
TI  - Therapist interventions in the interpersonal and cognitive therapy sessions of
      the Treatment of Depression Collaborative Research Program.
AB  - This report provides a descriptive evaluation of the therapist interventions
      implemented in the cognitive and interpersonal sessions of the Treatment of
      Depression Collaborative Research Program. 135,552 therapist statements drawn
      from 548 treatment sessions were coded for response mode category, time frame,
      and person. Therapists in both treatments were quite active, using predominantly
      clarifications, questions, and facilitative comments focused on the present time
      frame. The treatments also revealed important differences: cognitive therapists
      used more questions, restatements, and information/directional statements.
      Variance component analyses further revealed that differences between patients
      and between therapists explained a significant amount of variance in therapist
      response modes, indicating that manual-guided treatments can still reveal
      flexibility to address unique patient needs.

PMID- 11977783
TI  - The application of cognitive-behavioral therapy to counseling Chinese.
AB  - The purpose of this article is to discuss and analyze the application of
      Cognitive-Behavioral Therapy (CBT) to counsel Chinese. The analysis of the
      potential strengths and weaknesses of applying CBT in the treatment of Chinese
      clients are delineated based on the compatibility between the characteristics of
      CBT and Chinese culture. Modifications of CBT aiming at enhancing its
      effectiveness for Chinese within their cultural context are discussed. The study
      offers implications for clinical practice, training, and research.

PMID- 11977784
TI  - Exposure therapy for posttraumatic stress disorder.
AB  - Exposure therapy is a well-established treatment for Posttraumatic Stress
      Disorder (PTSD) that requires the patient to focus on and describe the details of
      a traumatic experience. Exposure methods include confrontation with frightening,
      yet realistically safe, stimuli that continues until anxiety is reduced. A review
      of the literature on exposure therapy indicates strong support from well
      controlled studies applied across trauma populations. However, there are many
      misconceptions about exposure therapy that may interfere with its widespread use.
      These myths and clinical guidelines are addressed. It is concluded that exposure
      therapy is a safe and effective treatment for PTSD when applied as directed by
      experienced therapists.

PMID- 11977785
TI  - Development and initial testing of a multimedia program for computer-assisted
      cognitive therapy.
AB  - A multimedia program for computer-assisted psychotherapy has been developed to
      help patients learn cognitive therapy skills. The program is designed to provide
      psychoeducation, teach self-help methods, and give information to clinicians on
      the patient's progress in using the software. Multimedia technology is utilized
      to engage users in the learning process and to make the program accessible for
      persons who do not have computer or keyboard skills. A preliminary study with 96
      subjects who used the software along with treatment as usual found that 75
      (78.1%) completed the entire program. Users indicated a high rate of acceptance
      of this form of computer-assisted therapy, and mean scores on a measure of
      cognitive therapy knowledge were significantly improved.

PMID- 11977786
TI  - Patient, therapist, and supervisor in a psychiatric institution: inner freedom
      and inner structure.
AB  - The authors discuss issues concerning the psychotherapeutic process in a
      psychiatric institution. They develop the concept of the institution as an
      internalized object in addition to its being an objective object. As such, it has
      an effect on the inner freedom and the internal structure of the patient, the
      therapist, and the supervisor. It is claimed that it is crucial for the
      development of an identity as a psychotherapist that the supervisor be aware of
      the institution as an inner and real object. The authors raise questions about
      what kind of "space" is possible in a psychiatric institution and what influence
      that may have on the therapeutic process. The impact on the therapist's
      professional identity is discussed. They point to the process of becoming a
      therapist via supervision and examine some relevant dilemmas. The authors
      conclude by discussing the duality of inner freedom and internal structure, and
      their specific manifestations within an institution.

PMID- 11977787
TI  - A bitter sweet pill.

PMID- 11977788
TI  - Competing for cash.

PMID- 11977789
TI  - Hands on care.

PMID- 11977790
TI  - Knowing their station.

PMID- 11977792
TI  - On their way home.

PMID- 11977794
TI  - A safer way.

PMID- 11977793
TI  - Night fever.

PMID- 11977796
TI  - Pakistani women's perceptions and experiences of incontinence.
AB  - AIM: To investigate the perceptions and experience of Pakistani women who have
      urinary incontinence problems. METHOD: Data were collected from a sample group of
      six Pakistani women with incontinence problems. A female Miripuri Punjabi speaker
      conducted and recorded semi-structured interviews with the women. The interviewer
      interpreted these recordings onto another tape. Data were then analysed and
      categorised. RESULTS: The women had low self-esteem and also felt sinful because
      of their incontinence. Muslim women are obliged to perform ritual cleansing and
      prayer five times a day. If they pass urine or faeces, or experience
      incontinence, they become unclean and prayer is denied until the act of ritual
      cleansing is repeated. The women used prayer to relieve stress caused by
      incontinence, but being unclean denied them this comfort, thus increasing stress.
      Some participants had become secretive and isolated. The women had developed
      three strategies to help them live with incontinence: risk reduction to reduce
      the number of incidents; management, which focused on coping with incontinent
      episodes; and problem-sharing with other women. Their inhibitions and language
      limitations prevented them from disclosing their problems clearly to health
      professionals and fully understanding advice they received. These inhibitions
      were reduced when they were treated by a female health professional. Having an
      interpreter present also increased satisfaction with treatment. CONCLUSION: To
      provide an effective continence service to Pakistani women with incontinence, it
      is necessary for healthcare professionals to understand their cultural and
      religious identities.

PMID- 11977798
TI  - Career pathways in research: clinical research.
AB  - This article, the second in a series on career pathways, informs readers of the
      knowledge they require to conduct clinical therapeutic trials to recognised
      standards. Many nurses start their careers in research as clinical research
      nurses. The skills and knowledge they develop through conducting multi-centre
      studies gives them an excellent grounding in the discipline, organisation and
      management of research.

PMID- 11977799
TI  - Osteogenesis imperfecta: an overview.
AB  - Osteogenesis imperfecta (brittle bone disease) is a rare hereditary disorder with
      an increased tendency to fracture. Chris Clark highlights the management needs of
      people with this condition.

PMID- 11977805
TI  - Cryosurgery for recurrent prostate cancer following radiation therapy.
AB  - Patients with prostate cancer are commonly treated medically or undergo radical
      prostatectomy and/or radiation therapy. Radiation therapy is usually selected for
      patients with local or regional disease and patients for whom traditional surgery
      has failed. The local recurrence of cancer in patients treated with radiation
      therapy presents a difficult challenge regarding the selection of further
      treatment options. A commonly applied treatment is salvage prostatectomy, but it
      can be difficult and complicated, with positive surgical margins occurring in as
      many as 50 percent of patients and with significant postoperative morbidity.
      Hormonal therapy, which is not curative, has served as an alternative to surgery
      in patients who have failed to respond to radiation therapy. Cryosurgery, the
      destruction of diseased tissue by freezing, is increasingly used both as a first
      line therapy and as a second-line therapy (salvage therapy) in patients for whom
      radiation therapy has failed. Recent reports suggest that cryosurgery may be a
      useful alternative procedure for treating some of these patients with recurrent
      cancers. Outcomes of cryosurgery are improving through better instrumentation,
      surgical technique, and experience. The available data suggest that some patients
      with radioresistant cancer appear to benefit from the use of cryosurgery as a
      salvage therapy. Use of this technique has resulted in biochemical disease-free
      survival for varying periods of some patients who had recurrent prostate
      carcinoma following radiation therapy; however, morbidity remains high and
      relatively few patients have had adequate followup. Salvage cryosurgery
      prospective clinical trials are warranted and would help determine long-term
      survival benefits and make possible the comparison of cryotherapy patient
      survival rates with those of untreated biopsy-positive patients.

PMID- 11977806
TI  - A hybrid input-output approach to model metabolic systems: an application to
      intracellular thiamine kinetics.
AB  - Models of the dynamics of complex metabolic systems offer potential benefits to
      the deep comprehension of the system under study as well as for the performance
      of certain tasks. Unfortunately, dynamic modeling of a great deal of metabolic
      systems may be problematic due to the incompleteness of the available knowledge
      about the underlying mechanisms and to the lack of an adequate observational data
      set. In theory, a valid alternative to classical structural modeling through
      ordinary differential equations could be represented by input-output approaches.
      But, in practice, such methods, which learn the nonlinear dynamics of the system
      from input-output data, fail when the experimental data set is poor either in
      size or in quality. Such a situation is not rare in the case of metabolic
      systems. This paper deals with a hybrid approach which aims at overcoming the
      problems addressed above. More specifically, it allows us to solve the
      identification problems of the intracellular thiamine kinetics in the intestine
      tissue. The method, which is half way between the structural and input-output
      approach, uses the outcomes of the simulation of a qualitative structural model
      to build a good initialization of a fuzzy system identifier. Such an
      initialization allows us to efficiently cope with both the incompleteness of
      knowledge and the inadequacy of the available data set, and to derive an input
      output model of the intracellular thiamine kinetics in the intestine tissue. The
      comparison of the predictions of the intracellular thiamine kinetics obtained by
      the application of such a model with those obtained by traditional approaches,
      namely compartmental models, neural networks, and fuzzy systems, highlighted a
      better performance of our model. As the structural assumptions are relaxed, we
      obtained a model slightly less informative than a purely structural one but
      robust enough to be used as a simulator. The paper also discusses the
      interpretative potential offered by such a model, as tested on diabetic subjects.

PMID- 11977807
TI  - Disambiguating ambiguous biomedical terms in biomedical narrative text: an
      unsupervised method.
AB  - With the growing use of Natural Language Processing (NLP) techniques for
      information extraction and concept indexing in the biomedical domain, a method
      that quickly and efficiently assigns the correct sense of an ambiguous biomedical
      term in a given context is needed concurrently. The current status of word sense
      disambiguation (WSD) in the biomedical domain is that handcrafted rules are used
      based on contextual material. The disadvantages of this approach are (i)
      generating WSD rules manually is a time-consuming and tedious task, (ii)
      maintenance of rule sets becomes increasingly difficult over time, and (iii)
      handcrafted rules are often incomplete and perform poorly in new domains
      comprised of specialized vocabularies and different genres of text. This paper
      presents a two-phase unsupervised method to build a WSD classifier for an
      ambiguous biomedical term W. The first phase automatically creates a sense-tagged
      corpus for W, and the second phase derives a classifier for W using the derived
      sense-tagged corpus as a training set. A formative experiment was performed,
      which demonstrated that classifiers trained on the derived sense-tagged corpora
      achieved an overall accuracy of about 97%, with greater than 90% accuracy for
      each individual ambiguous term.

PMID- 11977808
TI  - Selective automated indexing of findings and diagnoses in radiology reports.
AB  - The recent improvements in capabilities of desktop computers and communications
      networks give impetus for the development of clinical image repositories that can
      be used for patient care and medical education. A challenge in the use of these
      systems is the accurate indexing of images for retrieval performance acceptable
      to users. This paper describes a series of experiments aiming to adapt the
      SAPHIRE system, which matches text to concepts in the UMLS Metathesaurus, for the
      automated indexing of image reports. A series of enhancements to the baseline
      system resulted in a recall of 63% but a precision of only 30% in detecting
      concepts. At this level of performance, such a system might be problematic for
      users in a purely automated indexing environment. However, if the ability to
      retrieve images in repositories based on content in their reports is desired by
      clinical users, and no other current systems offer this functionality, then
      follow-up research questions include whether these imperfect results would be
      useful in a completely or partially automated indexing environment and/or whether
      other approaches can improve upon them.

PMID- 11977809
TI  - Patient safety, potential adverse drug events, and medical device design: a human
      factors engineering approach.
AB  - Adverse drug events are the single leading threat to patient safety. Human
      factors engineering has been repeatedly proposed, but largely untested, as the
      key to improving patient safety. The value of this approach was investigated in
      the context of a commercially available patient-controlled analgesia device that
      has been linked with several alleged patient injuries and deaths. Several reports
      have stated that errors in programming drug concentration were made during these
      adverse drug events. A simulation of the commercially available interface was
      compared experimentally with a simulated prototype of a new interface designed
      according to a human factors process. Professional nurses, averaging over 5 years
      of clinical experience with the commercially available interface and only minimal
      experience with the new interface, programmed both interfaces. The new interface
      eliminated drug concentration errors, whereas the simulated commercially
      available interface did not. Also, the new interface led to significantly fewer
      total errors and faster performance. These findings may have broad implications
      for the design, regulation, and procurement of biomedical devices, products, or
      systems that improve patient safety in clinical settings.

PMID- 11977810
TI  - Heterogeneous database integration in biomedicine.
AB  - The rapid expansion of biomedical knowledge, reduction in computing costs, and
      spread of internet access have created an ocean of electronic data. The
      decentralized nature of our scientific community and healthcare system, however,
      has resulted in a patchwork of diverse, or heterogeneous, database
      implementations, making access to and aggregation of data across databases very
      difficult. The database heterogeneity problem applies equally to clinical data
      describing individual patients and biological data characterizing our genome.
      Specifically, databases are highly heterogeneous with respect to the data models
      they employ, the data schemas they specify, the query languages they support, and
      the terminologies they recognize. Heterogeneous database systems attempt to unify
      disparate databases by providing uniform conceptual schemas that resolve
      representational heterogeneities, and by providing querying capabilities that
      aggregate and integrate distributed data. Research in this area has applied a
      variety of database and knowledge-based techniques, including semantic data
      modeling, ontology definition, query translation, query optimization, and
      terminology mapping. Existing systems have addressed heterogeneous database
      integration in the realms of molecular biology, hospital information systems, and
      application portability.

PMID- 11977811
TI  - Extracting knowledge from dynamics in gene expression.

PMID- 11977812
TI  - Carers who cross a chasm.

PMID- 11977813
TI  - Breaking the cycle of bad news.

PMID- 11977814
TI  - Immediate access.

PMID- 11977815
TI  - Not to be sniffed at.

PMID- 11977816
TI  - Beauty business. Interview by Charlotte Alderman.

PMID- 11977817
TI  - All through the night.

PMID- 11977818
TI  - To die or not to die.

PMID- 11977819
TI  - Run for cover.

PMID- 11977820
TI  - Spasm in MS.

PMID- 11977821
TI  - Dehydration in the terminally ill patient.
AB  - BACKGROUND: Many healthcare professionals believe that dehydration is painful and
      uncomfortable for dying patients. There is increasing evidence to support the
      view that dehydration might aid comfort and reduce stress in the final days of
      terminal illness. The decision of whether or not to administer artificial
      hydration intravenously of subcutaneously causes much concern for healthcare
      professionals. The British Medical Association's 1999 guidance for decision
      making, Withholding and Withdrawing Life: Prolonging Medical Treatment, states
      that: '...the emotional and psychological burden on staff involved with
      withdrawing or withholding life-prolonging treatment should be recognised and
      adequate support mechanisms need to be available and easily accessible before,
      during and after decisions have been made. CONCLUSION: Raising awareness of the
      effects of dehydration in terminally ill patients will lead to a better
      understanding among staff on the ward. It will help them to further promote the
      comfort of dying patients and help relatives come to terms with this distressing
      situation.

PMID- 11977822
TI  - Career pathways in research: clinical practice.
AB  - This article, the first in a five-part series on career pathways, discusses the
      facility for nurses to develop their clinical expertise to consultant level,
      which is an exciting development on the career pathway for nurses in clinical
      practice. The introduction of consultant nurses has re-emphasised the need for
      experienced leadership in research and practice development in clinical settings.

PMID- 11977823
TI  - Minimising the risk of hospital transmission of pulmonary TB.
AB  - Pulmonary tuberculosis is a threat to other patients and healthcare workers in
      hospital settings. Laila King discusses the ways to minimise the risk of
      transmission.

PMID- 11977825
TI  - Leading with confidence.

PMID- 11977827
TI  - Happy accidents.

PMID- 11977834
TI  - [Methods for identification of HLA antigen polymorphisms].
AB  - The HLA complex is the most polymorphic genetic system in man yet known. The
      variability of the HLA antigens is given by the presence of many alleles of the
      HLA genes. Requirements for compatibility of HLA antigens in organ and bone
      marrow transplantations, and also in the determination of genetic risk factors in
      autoimmune diseases evoke strong pressure on progress in HLA typing methods,
      mainly for increasing their sensitivity and resolution. For typing of the HLA
      antigens there are used cellular, serological, biochemical and DNA methods. For
      HLA class I typing there following tests are used: cytotoxic test (serological),
      CML (cellular), 1D--IEF (biochemical), RFLP, SSO, SSP--PCR, and SBT (DNA
      methods). For HLA class II typing, cytotoxic test (cellular), MLC (serological),
      RFLP, SSO, SSP--PCR, and SBT (DNA methods) are used. DNA methods represent the
      modern trend in the area of HLA typing and it will probably replace larger part
      of other HLA typing techniques. In our article, we describe the principles of
      methods that are used for HLA typing.

PMID- 11977835
TI  - [Transplantation of highly purified CD34+ hematologic peripheral stem cells from
      haploidentical related donors in the treatment of children with non-malignant
      diseases].
AB  - BACKGROUND: Children suffering from rare inherited disorders can be cured using
      stem cell transplantation (SCT). For patients where HLA-identical donor could not
      be found, there is an excellent chance of identifying a family member who shares
      an identical haplotype with the patient but whose second haplotype is different.
      This situation is called an HLA-full haplotype mismatch. Risks of haploidentical
      transplantation are graft rejection and severe graft-versus-host disease (GVHD).
      Histocompatibility barriers can be overcome by infusing high doses of T-cell
      depleted peripheral CD34+ stem cells. METHODS AND RESULTS: Between December 1995
      and March 2000, 5 children with rare inherited disorders were transplanted using
      highly purified CD34+ stem cells from haploidentical parents at the 2nd
      Department of Pediatrics, University Hospital Motol, Prague. Two children
      suffered from severe combined immunodeficiency (SCID), one child from malignant
      osteopetrosis, Wiskott-Aldrich syndrome and hemophagocytic lymphohistiocytosis,
      respectively. Positive selection of peripheral CD34+ stem cells from G-CSF
      stimulated donors was performed using the method of immunoabsorbtion (CellPro) (n
      = 2) or immunomagnetic separation (CliniMACS) (n = 3). Donor type engraftment was
      achieved in 4 children. In one of them early graft failure has developed
      successfully managed by second SCT from the same donor. One child with SCID had
      primary graft failure. Mild acute GVHD with good response to steroid therapy
      developed in 2 children. Three children are alive and 2 of them are cured. Two
      children died due to post-transplant complications--CMV pneumonia and
      encephalitis. CONCLUSIONS: Transplantation of highly purified CD34+ stem cells
      from haploidentical parents is a reasonable therapeutic option for children with
      some specific nonmalignant disorders lacking HLA identical donor. Risks of this
      type of SCT are the graft failure and severe infectious complications due to slow
      immunological reconstitution in comparison with SCT from HLA identical donors.

PMID- 11977836
TI  - [5-year experience with the Heimox system in the treatment of patients with
      chronic respiratory insufficiency].
AB  - BACKGROUND: Long-term oxygen therapy using oxygen concentrators has been
      introduced in the Czech Republic as a standard method since October 1992. Since
      August 1996 there has been a possibility of treating patients with chronic
      respiratory insufficiency with devices exploiting liquid oxygen. In our study we
      analyzed a group of patients treated with Heimox system during the period August
      1996 to December 2000. METHODS AND RESULTS: Heimox system has been indicated in
      85 patients (49 males, 31 females and five children). Mean survival time was 10
      months, no patient survived three years. Two-year survival was 8.2% (7 patients)
      and one-year survival 17.6% (15 patients). Compared to our results in 1296
      patients treated with oxygen concentrators in 1996 (mean survival time 17.3
      months, four-year survival 3%, three-year survival 14.4%, two-year survival
      21.1%, one-year survival 26.0%) patients treated with Heimox system had shorter
      survival time. CONCLUSIONS: Indication criteria for Heimox system approve using
      this system for patients with terminal stage of pulmonary illness and therefore
      the survival time is very short.

PMID- 11977837
TI  - [Risk factors for transmission of hepatitis C in the the Czech population].
AB  - BACKGROUND: Recent reports from all over the world have repeatedly indicated a
      change in the incidence of individual risk factors for hepatitis C virus (HCV)
      infection transmission compared with the pattern in the late 1980s and early
      1990s. In the Czech Republic, HCV is very often referred to as an addicts'
      disease, rare in the general population. To establish the incidence of individual
      risk factors for HCV infection transmission in a group of patients on follow-up
      at the Department of Internal Medicine I. General University Hospital in Prague
      2. METHODS AND RESULTS: The group of patients included 216 individuals (127 men,
      89 women) with documented HCV infection. The mean age of the patients was 40.2
      years (10-81 years; SD 14.3). The risk factors were identified on the basis of
      evaluation of the patient's medical history, and/or their medical records if
      available. The presence of at least one of the following risk factors was
      regarded as the source of infection (the figure in brackets gives the incidence
      of the respective factor in the examined group in percent): blood product
      transmission (15%), intravenous drug injection (16%), inclusion into a regular
      dialysis program (12%), profession-related risk of transmission (10%), sexual
      contact with an infected individual (2%), surgery including dental surgery (14%),
      invasive examination (6%), and tattooing (1%). No risk factor for infection
      transmission was identified in 24% of cases. CONCLUSIONS: It has been shown a
      risk factor for infection transmission can be identified, through careful
      examination of medical history data, in the Czech population in as much as 76% of
      cases. An important finding is the fact the infection can be regarded as
      iatrogenic in as much as 57% of cases. Our data clearly show HCV infection is not
      exclusively a disease of intravenous drug addicts.

PMID- 11977838
TI  - [Birth weight and gestational age in relation to risk factors of social
      conditions and health status].
AB  - BACKGROUND: The participants of European Longitudinal Study of Pregnancy and
      Childhood (ELSPAC) are women permanently resident in Brno, whose expected term of
      delivery corresponded with the prelimited period. In midpregnancy, 3327 of them
      filled in two research questionnaires with data concerning their marital status,
      health, education, dwelling, their up-bringing and stress in childhood as the
      essential information for the study of birth weight and gestational age
      variations of expected newborns. METHODS AND RESULTS: Sharing the flat with the
      parental generation, heating with solid fuel or gas and more smokers at home
      meant the risk for antenatal development of foetus. A certain influence seemed to
      have the number of rooms, too. Education of the mother-to-be as well as that of
      her partner and partly of her mother, too, determined the birth weight. To a
      certain degree, partner's position in employment and his health status played
      also a role. An important factor predetermining the birth weight and gestational
      age was the marital status of the mother: in the best situation were children
      born in complete families and greatly handicapped were offsprings of single
      mothers not living with their partners. CONCLUSIONS: Small influence on the
      prenatal development had the medical history of mothers, character of the
      upbringing in their original families and presence stressogenic events occurring
      in their girlhood up to 18 years of age.

PMID- 11977839
TI  - [The history of IKEM. The Institute for Circulatory Disorders].

PMID- 11977840
TI  - [Coping styles and anxiety and physiological responses of teachers in stressful
      situations].
AB  - The relationship between coping styles and stress responses of teachers was
      examined in an experiment. With the scores of Manifest Anxiety and Marlowe-Crowne
      Social Desirability Scales, teacher-participants were classified into four groups
      of six each; repressor, sensitizer, low-anxious, and defensive-anxious. Then,
      they performed a word-association task, and were individually interviewed by a
      woman they met for first time. Intermittently during the sessions, the
      participant rated own state anxiety; heart rate (HR) and skin conductance level
      (SCL) were monitored; and reaction time and successful recall rate on the task
      were recorded. Results were as follows: Repressors showed high state anxiety and
      a significantly greater increase in HR, but a smaller increase in SCL than the
      others. In contrast, sensitizers showed low state anxiety and a significantly
      greater increase in SCL. The low-anxious showed high state anxiety at the
      beginning which decreased immediately, and remained at an intermediate and steady
      physiological arousal level, except SCL. The defensive-anxious showed low state
      anxiety and low HR. On the whole, it was suggested that coping styles could
      predict stress responses.

PMID- 11977841
TI  - [Development of Autogenic Training Clinical Effectiveness Scale (ATCES)].
AB  - The purpose of the present study was to develop a scale measuring clinical
      effectiveness of autogenic training. In Study 1, 167 undergraduates completed a
      survey of items concerning physical and mental states, which were thought to vary
      in the course of autogenic training. With item and factor analyses, 20 items were
      selected, and the resulting scale (ATCES) had high discrimination and clear
      factor structure. In Study 2, reliability and concurrent and clinical validity of
      the scale were examined with three groups of respondents: 85 mentally healthy, 31
      control, 13 clinical persons. The scale showed a high test-retest correlation (r
      = .83) and alpha coefficient (alpha = .86). ATCES had a Pearson correlation
      coefficient of r = .56 with General Health Questionnaire (GHQ-12), and r = .73
      with trait anxiety (STAI-T). And ATCES successfully discriminated the mentally
      healthy and clinical groups in terms of clinical effectiveness. These results
      demonstrated high reliability and sufficient concurrent and clinical validity of
      the new scale.

PMID- 11977842
TI  - [Examing varieties, the factor structure, and differentiations of the coping
      strategies of "agari" (stage fright) in its eliciting situations].
AB  - The present study reports coping strategies in 'agari' eliciting situations.
      'Agari' is a Japanese noun (the verb form is 'agaru'), referring to broad
      experiences including 'stage-fright', 'choking under pressure' and 'social
      anxiety'. Based upon the self-reports of 426 subjects, a 84-item questionnaire on
      the coping strategies for 'agari' was constructed. Another 361 subjects completed
      the questionnaire, and a factor analysis of their responses revealed seven
      primary factors: "autosuggestion", "physical exercise", "image", "avoidance",
      "positive thinking", "easygoing tolerance", and "unrelated behavior".
      Furthermore, a higher-order factor analysis was carried out and revealed that
      "positive-negative" and "physical-cognitive" higher-order factors explained seven
      primary factors. Next, hierarchical cluster analysis was performed and the
      results divided twelve 'agari' situations into three clusters of situations:
      "competition", "presentation requiring preparation", and "impromptu
      presentation". The "physical exercise" strategies were used particularly in
      "competition" clusters. The other clusters were divided in the appraisals of
      whether they could prepare or not. It is suggested that the coping strategies for
      'agari' depend upon the nature of 'agari' eliciting situations.

PMID- 11977843
TI  - [Presence/absence of original information in the misleading information effect:
      an investigation using recognition and priming tasks similar to original
      information presentation].
AB  - Several previous studies on the misleading information effect employed priming
      tasks to examine the presence/absence of original information. Given
      hyperspecificity of priming, however, it is questionable whether or not their
      priming tasks were sensitive enough to detect original information because their
      stimuli were perceptually different from the slides in the study phase. In the
      priming task of this research, we used slides whose perceptual properties were
      equivalent to those of the studied ones. In addition, we also conducted a yes-no
      recognition task using the same slides so that the results of these two tasks
      could be directly compared. The misleading information effect was replicated in
      the recognition task. Nevertheless, participants correctly recognized the
      original slides, whereas no priming effect was observed for those slides. These
      results suggest that although the original information survives the misleading
      information effect, its representation is modified so that only the yes-no
      recognition task, not the priming task, has access to it.

PMID- 11977844
TI  - [Synthesis of binocular disparity with motion parallax in depth slant perception:
      statistical efficiency approach].
AB  - Statistical efficiency approach is used in order to investigate sampling
      properties of both binocular disparity and motion parallax processes in depth
      slant perception and to examine the independent decisions model (Mulligan & Shaw,
      1980) consisting of these processes. We carried out two experiments in which each
      cue was displayed solely (i.e., single condition) and both cues were displayed
      simultaneously (i.e., multiple condition). A two-alternative forced-choice (2AFC)
      task was used under the situation where a Gaussian noise was added to the
      stimulus value of depth slant. Statistical efficiencies were calculated in each
      experiment. The results showed that sampling size from binocular disparity was at
      least comparable or larger by a factor of 2.5-3.5 with that from motion parallax
      and that efficiencies of the multiple condition considerably exceeded those of
      the single condition. This suggests invalidity of the independent decisions
      model.

PMID- 11977845
TI  - [Effects of focus on working memory].
AB  - Effects of focus on a target word during performance of the reading span test
      (RST) were investigated. A focus word in the sentence was defined as the most
      critical word with a core meaning to integrate the sentence. Two kinds of RST
      were compared. One was focus-RST (F-RST) in which the target word to be
      maintained was a focus word of the sentence. The other was a non-focus-RST (NF
      RST) in which the target word was not a focus word of the sentence, although the
      sentence did contain a focus word. Results showed that RST scores were found to
      be higher for F-RST than for NF-RST. Moreover, the effect of focus was proved to
      be dominant for low span subjects. Intrusion errors also increased in NF-RST.
      Sentence length effect, however, was not found. The results showed that low span
      subjects had severe deficits in making and updating the focus, which is critical
      for sentence comprehension.

PMID- 11977846
TI  - [The influence of aging on short-term and long-term memory in the continuous
      recognition paradigm].
AB  - The continuous recognition paradigm was employed to examine age-related
      performance deficit in short-term and long-term memory. Three age groups of
      people: young, young-old, and old-old, participated in the study, which used
      words of high and intermediate familiarity. With intervals used as criteria for
      separation of short-term (STM) and long-term (LTM) memory, hit rate and reaction
      time (RT) were computed separately. Although not significantly different in STM,
      hit rate in LTM decreased as the participant got older. No difference in RT for
      young-old and old-old groups was found for STM and LTM of high familiarity words,
      but the difference was significant for LTM of intermediate familiarity. RT was
      longer for intermediate than high familiarity words for both young-old and old
      old groups in LTM, and only for old-old group in STM. These results indicated
      that although age differences in memory performance were not very large,
      different influence of aging on encoding, storage, and retrieval processes could
      be inferred.

PMID- 11977847
TI  - [Working memory for movement patterns: a direct comparison of memory spans for
      body and hand movements in dual-task situations].
AB  - In this experiment, 36 participants engaged in one of three span tasks; digit
      span, body movement span, or hand movement span task, in which they were asked to
      remember visually presented sequences of digits, whole body movement patterns, or
      hand movement patterns, respectively. As in a standard memory span procedure, the
      items within each sequence were recalled in order. Participants were presented
      with increasingly longer sequences of the items, and span score was defined as
      the number of items in the longest sequence a participant could recall perfectly.
      The span tasks were tested under three concurrent task conditions; no concurrent
      task control, concurrent articulation task, and concurrent body-related movement
      task. The concurrent movement task interfered with performance on both body
      movement and hand movement span tasks, but not on the digit span task, while the
      concurrent articulation task interfered with performance on all of the three span
      tasks. It is suggested that memory for movement patterns, which is involved in
      the body and band movement spans, would be mediated by a common motor-processing
      system.

PMID- 11977848
TI  - [Effects of kana-level neighbors and phoneme-level neighbors on lexical decision
      of Japanese katakana words].
AB  - This study examined the effect of neighborhood size on the recognition of
      Japanese katakana words. Neighbors of a given katakana word were defined in two
      ways; kana-level neighbor is a katakana word that can be constructed by changing
      one letter of the target word preserving the other letter positions, and phoneme
      level neighbor is a katakana word that can be created by changing one phoneme
      (consonant or vowel) preserving the other phoneme positions of the target. In
      Experiment 1, 30 university students participated in a lexical decision task and
      numbers of kana-level neighbor were manipulated. The result showed that the
      number of kana-level neighbor had an inhibitory effect on lexical decision of low
      familiarity katakana words. In Experiment 2, 30 university students participated
      in a lexical decision task and numbers of phoneme-level neighbor were
      manipulated. The result showed that the number of phoneme-level neighbor had no
      effect on lexical decision of katakana words. These results suggest that
      neighbors affect each other on their orthographic representation in the
      recognition of low familiarity Japanese katakana words.

PMID- 11977849
TI  - [A study of general public's trust in government and corporation in the issues of
      defense and nuclear power policies].
AB  - This study examined general public's trust in national government and electric
      power companies in terms of nuclear power policies, and that in the government in
      terms of defense policies. A questionnaire was distributed to a sample of 560
      Kobe citizens, and a total of 409 complete it. Covariance structure analysis was
      performed to test hypotheses of the present study. Results suggested that the
      more demanding of the government and corporations, the lower the person's trust.
      How well the person understood the difficulty of the work involved hardly
      affected his/her demand and trust in all three actors of the two issues. Results
      also indicated that the person who perceived the government to be under pressure
      to appear trustworthy tended to have lower trust in them, that Yamagishi's
      general trust (1998) did not influence the trust in the cases, and that awareness
      of popular political empowerment had a negative impact on the trust in the
      government.

PMID- 11977850
TI  - [Connectionist modeling of higher-level cognitive processes].
AB  - Connectionist modeling is one approach to understanding human intelligence using
      simulated networks of neuron-like processing units. In this article, we report on
      recent progress in connectionist models that simulate empirical data of higher
      level cognitive processes, these being memory, learning, language, thinking,
      cognitive development, and social cognition. We also review and summarize the
      advantages and disadvantages of these connectionist models. The computational
      framework of connectionist modeling has the potential to integrate specialized
      psychological findings of different areas using the same architectures and local
      functions of units and connections, inspired from neuroscience. In particular,
      the problems of dealing with structured information in distributed form, and
      doing tasks that require variable binding in connectionist networks are discussed
      from several different perspectives. As one possible solution to treat systematic
      mental representations properly, the symbolic connectionist model, which is a
      hybrid approach using symbolic representations and connectionist architectures,
      is explained. We argue that connectionist computer simulation offers significant
      benefits for today's psychological researches, and that connectionist modeling is
      likely to have an important influence on future studies.

PMID- 11977851
TI  - High-cost sepsis drug forces pharmacists to weigh patients' future.

PMID- 11977852
TI  - Drug shortages frustrate health care providers.

PMID- 11977853
TI  - IOM deems anthrax vaccine safe, effective.

PMID- 11977854
TI  - Pharmaceutical services in an HIV clinic.
AB  - Pharmaceutical-related interventions in a pharmacist-directed human
      immunodeficiency virus (HIV) clinic were characterized. Intervention types,
      clinical significance, and expected outcomes were adapted from the literature.
      Pharmacists' interventions were recorded on a spreadsheet, and two pharmacists
      came into agreement to ensure the consistency of categorization. Intervention
      types, clinical significance, expected outcomes, and types of therapy
      precipitating interventions were summarized. The number of patients seen was
      totaled, and the number of interventions per patient per visit was calculated.
      The average number of medications and CD4+ lymphocyte counts throughout the study
      were obtained through the Veterans Affairs Medical Center computer patient record
      system. A total of 70 patients received pharmaceutical services during the four
      year period. Each patient received an average of seven medications and two
      interventions. The most common interventions were medication counseling (39%),
      recommendations of monitoring parameters (17%), and prescription processing (9%).
      The majority of interventions were clinically significant (89%) and enhanced
      treatment efficacy (62%). The percentage of antiretroviral therapy-related and
      HIV-related interventions fluctuated over the study period, while the percentage
      of non-HIV-related interventions increased. Pharmacists' interventions and direct
      patient care at an HIV clinic effectively ensured patient adherence to treatment
      and provided clinical benefits for patients.

PMID- 11977855
TI  - Stability of calcitonin salmon in nasal spray at elevated temperatures.
AB  - The stability of calcitonin salmon in calcitonin salmon nasal spray at elevated
      temperatures was studied. Vials of calcitonin salmon nasal spray (2200 IU/mL)
      were stored for three days at 25, 40, or 60 degrees C or for three days at the
      same temperatures followed by two weeks at 5 degrees C and two additional weeks
      at 25 degrees C. Concentrations of calcitonin salmon and calcitonin C (a
      degradation product) were determined relative to a calcitonin salmon reference
      standard by high-performance liquid chromatography. Calcitonin salmon was stable
      under all study conditions except initial storage at 60 degrees C followed by two
      weeks at 5 degrees C and two weeks at 25 degrees C. The stability results were
      the same when determinations were made in terms of calcitonin C, which exceeded a
      5% concentration only for samples stored for the extended period after initial
      storage at 60 degrees C. Calcitonin salmon remained stable in nasal spray after
      being stored for three days at 25 or 40 degrees C followed by two weeks at 5
      degrees C and two weeks at 25 degrees C. Stability was lost during extended
      storage after initial storage at 60 degrees C.

PMID- 11977856
TI  - Providing nighttime pharmaceutical services through telepharmacy.
AB  - A nighttime telepharmacy service serving a community hospital is described. At a
      340-bed acute care community hospital, the level of nighttime activity related to
      medication use did not support the establishment of a full night pharmacy shift.
      After-hours access to medications was mostly the responsibility of nursing and
      medical staff using a separate night closet, automated dispensing machines, and
      limited floor stock. Pharmacists reviewed new orders and missing doses during the
      following day shift. An innovative practice model that combined an outsourced
      telepharmacy service and the traditional oncall pharmacist service was
      implemented to improve services at night. Prospective order review, drug
      information services, and clinical pharmacy consultations were all provided under
      the new model. Nurses and physicians used the service extensively. A total of
      1039 drug orders were reviewed by the telepharmacy service during the first three
      months, with 29% of these orders representing high-risk therapies. Most orders
      were submitted by the critical care areas, the medical-surgical units, and the
      emergency department. Feedback from the hospital staff concerning the service was
      favorable, and physician leaders asked that the service be expanded to take oral
      orders from physicians at night. A nighttime telepharmacy service was
      successfully implemented at a community hospital to provide medication order
      review, resolution of drug-related problems, and drug information and clinical
      pharmacy services.

PMID- 11977857
TI  - Continuing-education programs in pharmacogenomics for pharmacists.
AB  - The Notes section welcomes the following types of contributions: (1) practical
      innovations or solutions to everyday practice problems, (2) substantial updates
      or elaborations on work previously published by the same authors, (3) important
      confirmations of research findings previously published by others, and (4) short
      research reports, including practice surveys, of modest scope or interest. Notes
      should be submitted with AJHP's manuscript checklist. The text should be concise,
      and the number of references, tables, and figures should be limited.

PMID- 11977858
TI  - Developing and implementing a pharmacist-managed, telephone-based Helicobacter
      pylori clinic.

PMID- 11977860
TI  - Digital scanning and consolidated entry of medication orders in a multihospital
      health system.

PMID- 11977859
TI  - Rhabdomyolysis due to probable interaction between simvastatin and ritonavir.
AB  - Straightforward reports of unusual drug experiences are included in this section.
      While selected references may be cited, the purpose of a Drug Experience report
      is not to present an extensive review of the literature. A related section, Grand
      Rounds; includes papers that are well-documented patient case reports with a
      thorough review of the important literature to help put the case in perspective.
      Authors should report serious adverse drug reactions to the FDA medical products
      reporting program (MedWatch). Such reporting will not jeopardize the chances that
      AJHP will publish manuscripts on the same drug reactions.

PMID- 11977861
TI  - Strategies for minimizing antimicrobial resistance.
AB  - Various interventions for reducing antimicrobial resistance are described.
      Prudent and appropriate use of antimicrobials may help reduce the selective
      pressure that promotes the emergence of resistance. Limiting antimicrobial use
      for the promotion of growth in animals may also decrease the potential for
      transmission of resistant microorganisms to humans through the food supply.
      Clinical practice guidelines provide a standard of care for the use of
      antimicrobials in specific infectious syndromes, promoting appropriate
      antimicrobial use. Excluding certain antimicrobials from institutional
      formularies and restricting prescribing of some agents or classes of agents
      included in the formulary may reduce the emergence of resistance. Therapeutic
      failure can be avoided by considering pharmacokinetic and pharmacodynamic factors
      when selecting an antimicrobial regimen. A sufficient dose and an appropriate
      administration interval are necessary to ensure that the antimicrobial
      concentration at the site of infection is high enough to kill or inhibit the
      growth of the pathogen. Routine antimicrobial susceptibility surveillance can
      detect the emergence of resistant pathogens and allow for prompt intervention.
      Implementation of infection control practices can prevent or stem outbreaks of
      infection caused by resistant microorganisms. Vaccinations may reduce
      antimicrobial resistance indirectly by decreasing the need for antimicrobial
      therapy. Antimicrobial resistance can be reduced through a combination of
      interventions. The management of antimicrobial resistance requires a
      multidisciplinary approach, including participation from physicians, nurses,
      pharmacists, and infection control and housekeeping staff.

PMID- 11977862
TI  - Role of JCAHO standards and clinical practice guidelines in promoting appropriate
      antimicrobial use.
AB  - The role of the Joint Commission on Accreditation of Healthcare Organizations
      (JCAHO) standards and clinical practice guidelines in promoting appropriate
      antimicrobial use and the development of such standards and guidelines are
      described. JCAHO is committed to continuously improve the safety and quality of
      patient care. Reducing antimicrobial resistance in health systems often requires
      change, something that many health care practitioners are reluctant to embrace.
      Current JCAHO standards suggest that the use of clinical practice guidelines be
      considered, but guideline use is not required. JCAHO's standards development
      process is lengthy and involved. Therefore, it is easier to effect change by
      modifying the statements of intent that accompany the standards than the
      standards themselves. Concerns about antimicrobial resistance can be addressed
      through performance measurement. In July 2002, core measures of patient care
      processes and outcomes will be implemented for the first time. JCAHO requires
      hospital laboratories to be accredited, which increases the stature of the
      laboratory in the eyes of hospital administration. JCAHO laboratory standards
      directly relate to clinical practice guidelines, antimicrobial resistance, and
      NCCLS (formerly known as the National Committee for Clinical Laboratory
      Standards) and support efforts to reduce inappropriate antimicrobial use.
      Hospital laboratories play a vital role in effecting change in antimicrobial use.
      JCAHO laboratory standards for clinical practice guidelines and quality control
      support efforts to reduce inappropriate antimicrobial use. Hospitals have been
      reluctant to require the use of clinical practice guidelines in JCAHO standards,
      although guidelines promote appropriate antimicrobial use and reduce
      antimicrobial resistance. Pharmacists should work with laboratory staff and JCAHO
      to effect the changes needed to stem antimicrobial resistance.

PMID- 11977863
TI  - Assessing the impact of antimicrobial resistance.
AB  - Trends in infectious disease mortality, contributing factors, and resistance
      patterns of commonly isolated microorganisms are described. Antimicrobial
      resistance was first reported in 1941 with sulfonamides. The frequency of
      antimicrobial resistance has increased in hospital and community settings,
      resulting in therapeutic failures, the use of increasingly costly and toxic
      antimicrobials, extended hospital stays, and increased morbidity, mortality, and
      health care costs. Retrospective analysis of infectious disease mortality in the
      United States reveals that resistance has increased despite the development of
      new antimicrobials. Factors contributing to antimicrobial resistance include
      patients' expectations of receiving an antimicrobial prescription after an office
      visit (even when one is not warranted), low vaccination rates among the elderly,
      international travel, and continuous exposure to small amounts of antimicrobials
      in the food supply. Analysis of susceptibility and resistance patterns of more
      than 10.3 million isolates found that 36%, 30%, and 31% of Escherichia coli
      isolates were resistant to ampicillin, ampicillin-sulbactam, and piperacillin,
      respectively. E. coli and Klebsiella pneumoniae exhibited reduced susceptibility
      to ceftazidime in certain regions of the country. Pseudomonas aeruginosa
      exhibited resistance to ciprofloxacin, imipenem, gentamicin, and ceftazidime. The
      occurrence of ciprofloxacin- and levofloxacin-resistant Staphylococcus aureus was
      similar, while the frequency of erythromycin-resistant S. aureus varied widely
      nationwide. Nationwide susceptibility to cefotaxime was significantly lower than
      that to ceftriaxone. Antimicrobial resistance is an increasing problem that
      contributes to morbidity, mortality, and increased health care costs. Analysis of
      susceptibility and resistance patterns of specific microorganisms is necessary to
      gain further insight into the causes of antimicrobial resistance and ways to
      reduce it.

PMID- 11977864
TI  - Role of NCCLS in antimicrobial susceptibility testing and monitoring.
AB  - The role of NCCLS (formerly known as the National Committee for Clinical
      Laboratory Standards) in establishing guidelines for antimicrobial susceptibility
      testing, NCCLS's consensus-building process, and new interpretive criteria for
      antimicrobial susceptibility testing for 2002 are described. When revising and
      developing new guidelines, NCCLS uses an extensive process to reach consensus,
      while considering the clinical relevance, cost, and other practical implications
      of the proposed guidelines. NCCLS groups antimicrobials for susceptibility
      testing and reporting on the basis of their clinical efficacy, known patterns of
      microbial resistance, strategies to minimize the emergence of resistance,
      consensus recommendations, and cost to avoid unnecessary testing. NCCLS
      guidelines address quality control issues and current methodologies, such as
      conventional disk diffusion and microbroth dilution tests. In addition, new
      testing methods for the detection and confirmation of special resistance
      mechanisms (e.g., extended-spectrum beta-lactamase production) are recommended.
      In 2002, the minimum inhibitory concentration breakpoints for resistance and
      susceptibility of Streptococcus pneumoniae to cefotaxime and ceftriaxone in
      nonmeningitis infection were increased to more accurately predict clinical
      outcomes. Implementation of new NCCLS guidelines requires the education and
      collaboration of the laboratory, pharmacy, and medical staff. The NCCLS consensus
      building process provides clinicians with clinically relevant and cost-effective
      strategies for antimicrobial susceptibility testing and reporting, guidelines and
      criteria for interpreting susceptibility test results, and guidelines for
      detecting emerging antimicrobial resistance. The use of specialized testing
      methods for detecting and confirming unusual or difficult-to-identify resistance
      mechanisms can improve the accuracy of reporting of resistance and avoid
      therapeutic failures. The implementation of new NCCLS guidelines requires
      collaboration and education of members of various institutional departments.

PMID- 11977865
TI  - Haemophilus influenzae type B vaccine update.

PMID- 11977866
TI  - A survey of the prevalence of domestic violence in rural and Urban South Dakota.

PMID- 11977867
TI  - A first exposure to domestic violence.

PMID- 11977868
TI  - Providing crisis counselors on-site to victims of domestic violence in the
      emergency department: a report of a local pilot project.
AB  - In order to facilitate appropriate referral and aftercare for victims of domestic
      violence who present to Sioux Falls hospital emergency departments, Children's
      Inn (a local domestic violence shelter) and city hospitals collaborated to
      develop a program to provide crisis counselors to these patients during their ED
      visits. This program, which has been in place for over two years, has provided
      services to 63 patients. These services include on-site counseling to the
      victims, assistance with filling out protection orders and with making police
      reports, and referral of many of the women to shelter and/or support groups.
      Having the crisis counselors meet and talk with these patients during the ED
      visit has facilitated the provision of these services to victims who otherwise
      may have been unable or hesitant to avail themselves of local resources.

PMID- 11977869
TI  - Measuring the impact of Parkinson's disease: an occupational therapy perspective.
AB  - Parkinson's disease is a common neurodegenerative disorder, affecting over
      100,000 Canadians. With advances in medical and surgical treatments, clients are
      living longer and fuller lives. However, as the disease progresses those with
      Parkinson's continue to face a variety of deficits in their occupational
      performance. Although this is the domain of occupational therapists, very little
      is described in the occupational therapy literature related to Parkinson's. This
      article addresses this void by describing these deficits and current measurement
      tools that can be used to evaluate the impact on people living with Parkinson's
      disease. Although several tools are cited, three tools are recommended for an
      occupational therapy evaluation of individuals with Parkinson's disease: the
      Canadian Occupational Performance Measure, the Unified Parkinson's Disease Rating
      Scale and the Parkinson's Disease Questionnaire.

PMID- 11977870
TI  - Attitudes that breed the vicious circle of fear and violence.

PMID- 11977871
TI  - Discharging older adults with a severe and chronic mental illness in the
      community.
AB  - In recent years, a deinstitutionalization movement has been occurring in Canadian
      psychiatric institutions. Occupational therapists, experts in evaluating
      occupational performance, are key contributors to the selection of appropriate
      community housing environments. This study describes the global functioning,
      performance in activities of daily living, social behavior, cognitive status, and
      quality of life of 33 older adults with a severe and chronic mental illness, who
      were transferred from a psychiatric hospital to community facilities between 1995
      and 1998. Evaluations were repeated five times, twice before discharge and three
      times after the transfer. Participants demonstrated stability in their global,
      social and ADL functioning over time. In general, participants required
      occasional intervention for management of social behaviors, moderate assistance
      in activities of daily living, and were highly satisfied with their community
      accommodation. The transfer to community settings did not lead to a significant
      deterioration in the participants' levels of global functioning and quality of
      life.

PMID- 11977872
TI  - Individualized outcome measures: a review of the literature.
AB  - The client-centred nature of occupational therapy acknowledges the individual as
      the central element of treatment. This philosophy, however, challenges the
      therapist to choose an outcome measure that is capable of reflecting this
      individualized perspective. Recent papers published in the rehabilitation
      literature have reported on the increased responsiveness of such measures over
      traditional self-report questionnaires. Although the need for a comprehensive
      review of individualized outcome measures has been identified in the literature,
      none exists to date. The purpose of this paper is to review six individualized
      outcome measures that have been identified in the rehabilitation and psychology
      literature. The measures include: the Canadian Occupational Performance Measure,
      the Assessment of Motor and Process Skills, McMaster (MAC) Toronto Arthritis,
      Goal Attainment Scaling, Target Complaints and the Patient Specific Functional
      Scale. The reliability, validity, responsiveness and clinical utility of each
      outcome measure was examined and critiqued. Each tool, to a varying degree, met
      the description of a standardized, client-centred outcome measure.

PMID- 11977873
TI  - Collaborative fieldwork education with student occupational therapists and
      student occupational therapist assistants.
AB  - The profession of occupational therapy has a long history of working
      collaboratively with support personnel. This paper describes the process of a
      fieldwork education partnership developed between the McMaster University, BHSc
      (OT) Program and the Mohawk College, Occupational Therapist Assistant and
      Physical Therapist Assistant Program. Eight student occupational therapists and
      eight student occupational therapist assistants learned together in a variety of
      fieldwork settings, either in pairs or in groups. Both groups of students kept
      weekly journals of the experience and completed a post placement questionnaire.
      The journals were inductively analysed using a retrospective content analysis.
      The four emergent themes identified from the data are learning about each other's
      role, collaborative learning, impact on client care and future practice, and
      resistance to roles. Recommendations for future collaborations are discussed.

PMID- 11977874
TI  - Imaging body armor.
AB  - This study examined the feasibility of performing radiographic studies on
      patients wearing standard-issue body armor. The Kevlar helmet, fragmentation
      vest, demining suit sleeve, and armor plate were studied with plain film and
      computed tomography in a simulated casualty situation. We found that the military
      helmet contains metal screws and metal clips in the headband, but diagnostic
      computed tomographic images can be obtained. Kevlar, the principal component of
      soft armor, has favorable photon attenuation characteristics. Plate armor of
      composite material also did not limit radiographic studies. Therefore, when
      medically advantageous, patients can be examined radiographically while wearing
      standard military body armor. Civilian emergency rooms should be aware of these
      observations because law enforcement officers wear similar protective armor.

PMID- 11977875
TI  - Sexual behaviors and human immunodeficiency virus infection among Thai army
      conscripts between 1992 and 1998.
AB  - This study examined changes in sexual behavior among Thai army conscripts from
      1992 to 1998 in association with human immunodeficiency virus (HIV)
      seroprevalence. The sexual behavior survey was started in 1992 during the
      epidemic of HIV infection in Thailand, when sexual transmission was the most
      common route and young men were at high risk, and it has continued yearly since
      1995. The self-reported questionnaires were administered to randomly selected
      conscripts (N = 294 in 1992, N > 4,000 in 1995-1998), and trends in sexual
      behaviors were studied. The results showed that risky sexual behaviors generally
      decreased in relation to the decline in HIV seroprevalence, but the conscripts
      still engage in risky sexual behaviors. Appropriate interventions should be
      implemented to change these behaviors. The periodic sexual behavior surveys will
      be useful in evaluating program outcomes and planning for future interventions.

PMID- 11977876
TI  - Teaching military medicine: enhancing military relevance within the fabric of
      current medical training.
AB  - The education of military medical students and house officers in military
      relevant curricular elements is increasingly important given the greater
      frequency with which military physicians are deployed to field and operational
      settings. However, the common approaches of either expanded didactic sessions or
      implementation of operational rotations for trainees face competition from
      instruction in other aspects of medicine that are essential for all (military as
      well as nonmilitary) physicians. We describe efforts to integrate military
      relevant education within the existing framework of medical education, including
      current inpatient and ambulatory care rotations. This approach complements the
      formal, didactic syllabus, avoiding potential conflict engendered by eliminating
      curricular elements to accommodate military-unique subjects.

PMID- 11977877
TI  - Evaluation of exertional dyspnea in the active duty patient: the diagnostic
      approach and the utility of clinical testing.
AB  - INTRODUCTION: Minimal information currently exists on how clinicians should
      approach the evaluation of the young patient with exertional dyspnea. The
      objective of this study was to determine the frequency of specific diseases and
      the most useful tests to establish the diagnosis in an active duty military
      population presenting with exertional dyspnea. METHODS: A total of 105 active
      duty military patients with complaints of exertional dyspnea and 69 active duty
      military asymptomatic controls were evaluated at a pulmonary disease clinic at an
      Army tertiary care center. All patients and controls underwent a standard
      evaluation that included history, physical examination, chest radiography (CXR),
      arterial blood gas testing, laboratory testing, full pulmonary function testing
      (PFT), inspiratory and expiratory pressure determinations, methacholine challenge
      testing, cardiopulmonary exercise testing, electrocardiography, and
      echocardiography. RESULTS: Obstructive lung disease was found in 52% of patients
      (35% with exercise-induced asthma and 12% with asthma), 10% had vocal cord
      dysfunction, and 14% had other diagnoses. Twenty-four percent of patients had no
      specific diagnosis. Methacholine challenge testing yielded a positive diagnosis
      in 41% of patients and spirometry in 16%. Other pulmonary tests were of limited
      value, with abnormal values of 11.4% for full PFT, 2.9% for arterial blood gas
      testing, and 0.4% for CXR. Laboratory evaluation yielded positive results in less
      than 5% of patients, and cardiac evaluation was normal in all patients.
      CONCLUSIONS: Various forms of obstructive lung disease and vocal cord dysfunction
      were the most common findings in this group. The routine use of spirometry and
      bronchoprovocation testing is warranted, but other tests, such as full PFT, CXR,
      and cardiac and laboratory evaluations, have limited diagnostic value in this
      population.

PMID- 11977878
TI  - A method for training combat medics during stability and support operations.
AB  - Regardless of the conflict situation, highly trained combat medics (medics
      assigned in maneuver units) are a combat multiplier for military operations.
      Keeping medics (and physicians) well trained and motivated has many challenges,
      and we propose a program of instruction in six different nationally recognized
      courses to address these concerns and achieve the objective of providing medical
      training in this environment. We tested our program during our recent deployment
      to Kosovo. A total of 138 certifications were given during a 30-day period to 90%
      of our population of 120 medics.

PMID- 11977879
TI  - Major General Paul H. Streit, the first military otolaryngologist.

PMID- 11977880
TI  - The relationship between air particulate levels and upper respiratory disease in
      soldiers deployed to Bosnia (1997-1998).
AB  - The objective of this study was to determine whether there was a relationship
      between levels of particulate matter with an aerodynamic diameter of less than 10
      microns (PM10) and upper respiratory disease (URD) rates in soldiers deployed to
      Bosnia in 1997 and 1998. PM10 levels were divided into quartiles and upper and
      lower 50th percentiles. When all camps were combined, there was a statistically
      significant association between the PM10 maximum level and URD rates based on
      Kruskal-Wallis and Mann-Whitney U tests, and the Pearson correlation was
      statistically significant. Although the relationship was not statistically
      significant in analyses conducted of the individual camps, the average URD rate
      increased with each quartile of PM10 maximum exposure. There was no statistically
      significant association between PM10 average exposure and URD rates, although the
      average URD rate increased with each quartile of PM10 average exposure. Although
      these results are not conclusive, there appears to be a relationship between PM10
      levels and URD rates in soldiers deployed to Bosnia in 1997 and 1998.

PMID- 11977881
TI  - Recent trends in workload, input costs, and expenditures in the Air Force Medical
      Service Direct Care System.
AB  - A study was conducted to examine the relationship between two types of trends in
      the Air Force Medical Service Direct Care System (AFMS/DCS): trends in
      expenditures, total and by categories; and trends in medical workload, defined as
      the sum of inpatient admissions and outpatient clinic visits. Expenditure and
      medical workload data were extracted from the Medical Expense and Performance
      Reporting System Executive Query System. Medical inflation data were obtained
      from the Bureau of Labor Statistics Producer Price Index series. Between fiscal
      years 1995 and 1999, the AFMS/DCS experienced a 21.2% decrease in medical
      workload, but total (nominal) expenditures declined only 3.6%. Of all expenditure
      categories, only inpatient medical care, outpatient medical care, and military
      funded private sector care for active duty personnel (supplemental care) have any
      direct relationship with AFMS/DCS medical workload. Real expenditures for the
      three categories above decreased by 20.3% during the 5-year period. Accounting
      for inflation and considering only expenditures related to medical workload,
      these results suggest that the AFMS/DCS is spending approximately 20% less money
      to do approximately 20% less work.

PMID- 11977882
TI  - Recognition of depressive disorders by primary care providers in a military
      medical setting.
AB  - This study examined the accuracy of military primary care providers in detecting
      depressive disorders in their patients. For a 5-day period, each patient who
      entered the primary care clinic completed the depression section of the Patient
      Health Questionnaire (PHQ). Appointment notes were examined for depressive
      disorder diagnoses and then compared with PHQ responses. Of 337 respondents, 19
      (5.6%) were identified by the PHQ as meeting the criteria for major depression; 4
      (21%) of these 19 were identified by their provider as having a major depressive
      disorder. Eighteen (5.3%) were identified as having minor depression by the PHQ;
      none of these individuals were identified by their provider as having minor
      depression. These results suggest that military primary care providers, like
      their civilian counterparts, are not diagnosing depressive disorders as
      frequently as they present. Given the financial, medical, and personal
      consequences of not recognizing and treating depressive disorders, suggestions
      for increasing appropriate depression diagnoses are discussed.

PMID- 11977883
TI  - A mathematical model of hemorrhagic shock: the future of trauma triage.
AB  - Trauma scores have attempted for decades to identify individuals likely to
      survive a traumatic insult. However, current systems are limited because they do
      not account for the complex physiologic mechanisms that unfold after a traumatic
      event. This article describes a new technique in trauma scoring that models these
      interdependent mechanisms and thereby seeks to predict the patient's ultimate
      short-term outcome and survival time based on the severity of the traumatic
      insult. This model uses three parameters in a system of ordinary differential
      equations to make this prediction: mean arterial pressure, neurologic function,
      and systemic acidosis/base deficit. This study demonstrates the accuracy of this
      model compared with known survival time data from previous animal studies. This
      model represents a new prognostic tool that can easily be integrated into a
      computer software package designed to facilitate quick and accurate triage
      decisions.

PMID- 11977884
TI  - Tuberculosis skin test conversion rates evaluated at an overseas military
      hospital.
AB  - As a result of a perceived increase in purified protein derivative skin test
      converters, purified protein derivative skin testing of hospital staff and
      epidemiological evaluation were undertaken. A possible common source of
      tuberculosis exposure was identified and evaluated. This patient was skin test
      positive but never provided prophylactic treatment in Spain, and normal case
      management procedures failed. The Andalusia region, where the naval base is
      located, has a reported rate of about 15 new tuberculosis cases per 100,000
      persons per year, whereas the rate for the entire country of Spain is 22 per
      100,000 persons. More than half of the new cases of tuberculosis reported in
      Spain come from this region. As a result of this work, improved personal
      prevention programs were instituted and hospital and base orientation regarding
      the unique risk of tuberculosis in this region was improved.

PMID- 11977885
TI  - Epidemiologic and ecologic characteristics of some diseases transmitted by
      arthropods on the littoral of the Republic of Croatia.
AB  - OBJECTIVE: To show epidemiologic and ecologic characteristics of some diseases
      transmitted by arthropods on the littoral of the Republic of Croatia. METHODS:
      The pattern of infectious diseases that are transmitted exclusively by vectors
      was monitored during the period 1985 to 1999. Data on the incidence of the
      diseases in the Republic of Croatia as a whole and available data on the presence
      of the vectors for the diseases on the littoral are presented for comparison.
      RESULTS: Mediterranean spotted fever, murine typhus, Lyme disease, cutaneous and
      visceral leishmaniasis, and pappataci fever occur sporadically on the Croatian
      littoral. Tick-borne meningoencephalitis is endemic in the northwestern part of
      Croatia but is not present on the littoral. Twelve cases of malaria are imported
      into Croatia per year on average. CONCLUSION: Diseases transmitted by arthropods
      are not a major public health problem in Croatia. The medically relevant
      entomofauna of Croatia has not yet been adequately investigated.

PMID- 11977886
TI  - International use of an academic nephrology World Wide Web site: from medical
      information resource to business tool.
AB  - BACKGROUND: Studies of the use of the World Wide Web to obtain medical knowledge
      have largely focused on patients. In particular, neither the international use of
      academic nephrology World Wide Web sites (websites) as primary information
      sources nor the use of search engines (and search strategies) to obtain medical
      information have been described. METHODS: Visits ("hits") to the Walter Reed Army
      Medical Center (WRAMC) Nephrology Service website from April 30, 2000, to March
      14, 2001, were analyzed for the location of originating source using Webtrends,
      and search engines (Google, Lycos, etc.) were analyzed manually for search
      strategies used. RESULTS: From April 30, 2000 to March 14, 2001, the WRAMC
      Nephrology Service website received 1,007,103 hits and 12,175 visits. These
      visits were from 33 different countries, and the most frequent regions were
      Western Europe, Asia, Australia, the Middle East, Pacific Islands, and South
      America. The most frequent organization using the site was the military Internet
      system, followed by America Online and automated search programs of online search
      engines, most commonly Google. The online lecture series was the most frequently
      visited section of the website. Search strategies used in search engines were
      extremely technical. CONCLUSIONS: The use of "robots" by standard Internet search
      engines to locate websites, which may be blocked by mandatory registration, has
      allowed users worldwide to access the WRAMC Nephrology Service website to answer
      very technical questions. This suggests that it is being used as an alternative
      to other primary sources of medical information and that the use of mandatory
      registration may hinder users from finding valuable sites. With current Internet
      technology, even a single service can become a worldwide information resource
      without sacrificing its primary customers.

PMID- 11977887
TI  - The evolution of a health hazard assessment database management system for
      military weapons, equipment, and materiel.
AB  - During the 1970s, the Army health hazard assessment (HHA) process developed as a
      medical program to minimize hazards in military materiel during the development
      process. The HHA Program characterizes health hazards that soldiers and civilians
      may encounter as they interact with military weapons and equipment. Thus, it is a
      resource for medical planners and advisors to use that can identify and estimate
      potential hazards that soldiers may encounter as they train and conduct missions.
      The U.S. Army Center for Health Promotion and Preventive Medicine administers the
      program, which is integrated with the Army's Manpower and Personnel Integration
      program. As the HHA Program has matured, an electronic database has been
      developed to record and monitor the health hazards associated with military
      equipment and systems. The current database tracks the results of HHAs and
      provides reporting designed to assist the HHA Program manager in daily
      activities.

PMID- 11977888
TI  - Three-dimensional phase-contrast magnetic resonance angiography: a useful
      clinical adjunct to gadolinium-enhanced three-dimensional renal magnetic
      resonance angiography?
AB  - OBJECTIVE: To assess the value of three-dimensional (3D) phase-contrast (PC)
      magnetic resonance angiography (MRA) after gadolinium (Gd)-enhanced 3D MRA for
      renal artery imaging. METHODS: Twenty-one patients with suspected renal artery
      hypertension were reviewed. All studies included Gd-enhanced 3D MRA and 3D PC
      MRA. Blinded interpretation of the images was performed for each technique
      independently and in combination. Conventional X-ray angiography was used for
      diagnostic correlation when available. RESULTS: Renal artery stenosis was present
      in 7 (16.3%) of 43 renal arteries, confirmed by X-ray angiography. MRA images
      demonstrated 100% sensitivity and 74% specificity for Gd-enhanced 3D MRA and 100%
      sensitivity and 94% specificity for 3D PC MRA. All vessels were diagnosed
      correctly when both image sets were viewed. CONCLUSION: 3D PC MRA can improve the
      specificity of renal MRA by decreasing the number of false-positive Gd-enhanced
      3D MRA interpretations.

PMID- 11977889
TI  - Simulation and the future of military medicine.
AB  - The U.S. military currently faces serious difficulties in training medical
      personnel in peacetime for the tasks of war. The military beneficiary population
      comprises fit young service men and women, their dependents, and retirees. Their
      peacetime care, although vital, does little to prepare military medical personnel
      for war. Medical commanders have instituted an array of training programs to
      compensate for this shortfall, but there remains a large gap between operational
      medical needs and training opportunities in peacetime. The military has begun to
      examine whether simulation can fill this gap. An array of commercial, off-the
      shelf technologies are already being used with varying degrees of success, and
      major initiatives are under way in both academia and industry, supported by the
      military, to develop virtual reality products for combat medical training. Even
      as the military exploits emerging technology and begins to articulate a
      simulation strategy, there is a growing interest in civilian medicine in the
      potential for simulation to affect patient safety--how medical simulation might
      mitigate the injuries and deaths caused by medical errors--and how it might also
      improve the quality of medical education and training.

PMID- 11977890
TI  - Rubber matting on an obstacle course causes anterior cruciate ligament ruptures
      and its removal eliminates them.
AB  - In June 1998, six unexpected anterior cruciate ligament (ACL) ruptures within 12
      months were detected by routine injury surveillance in a cohort of Australian
      Army recruits. Local investigation, reported separately as a Case Report in this
      issue, suggested the cause to be an excessive coefficient of friction between
      rubber boot soles and newly laid rubber matting on one obstacle course, creating
      excessive knee torques. The matting was removed progressively, but not before two
      more ruptures occurred on one remaining section. In this retrospective study, chi
      2 analyses were used to compare the incidence of ACL rupture in prehazard, hazard
      exposed, and postintervention cohorts, and the average costs to the institution
      of each ACL rupture were determined. Zero, eight, and zero ACL ruptures occurred
      in the prehazard, hazard-exposed, and postintervention cohorts, respectively (chi
      2 > 4.75 for 1 df, p < 0.03 for each change in incidence). The temporal
      relationships between hazard introduction or removal and changes in the incidence
      of ACL rupture were strong. The average institutional cost of each ACL rupture
      was AU$54,627 or US$34,322. Rubber matting on obstacle courses increases the risk
      of ACL rupture in the presence of speed and rubber-soled footwear. Routine injury
      surveillance and simple preventive processes save money and personnel.

PMID- 11977891
TI  - Injury surveillance and systematic investigation identify a rubber matting hazard
      for anterior cruciate ligament rupture on an obstacle course.
AB  - In June 1998, six unexpected anterior cruciate ligament ruptures within 12 months
      were detected by routine injury surveillance in a cohort of Australian Army
      recruits. A systematic investigative process was used to identify the probable
      cause. Review of the case histories, followed by on-site assessment of the common
      hazard, revealed that all ruptures occurred as recruits twisted or landed on
      newly laid rubber matting at one obstacle course. The matting was laid with the
      intention of countering ground wear, shock of impact, and slipping to reduce the
      risks of ankle sprain and stress fracture. Review of the literature indicated
      that the interface between the rubber boot sole and rubber matting was associated
      with a very high coefficient of friction, probably causing excessive torque at
      the knee. Similar mechanisms of anterior cruciate ligament injury have been
      reported in sports and skiing. A subsequent study of intervention effects,
      reported separately in this issue, was conducted to confirm the damaging role of
      the matting. Routine injury surveillance and systematic investigation are
      valuable tools for injury prevention. Clinicians are well equipped for both.

PMID- 11977892
TI  - A 20-year-old army private with leg pain, fever, and collapse during a forced
      road march.

PMID- 11977893
TI  - Epidemiology of injuries aboard a Greek warship.

PMID- 11977894
TI  - Misconceptions involving dental local anesthesia. Part 1: Anatomy.

PMID- 11977895
TI  - Misconceptions involving dental local anesthesia. Part 2: Pharmacology.

PMID- 11977896
TI  - A survey of fluoride in Texas well water.

PMID- 11977897
TI  - Organized dentistry's role in reversing the trend of decreasing enrollment of
      underrepresented minority dental students.

PMID- 11977898
TI  - Oral and maxillofacial pathology case of the month. Lateral periodontal cyst
      (LPC).

PMID- 11977899
TI  - Caring for the child--the pediatric dentist's dilemma. Response to Ethical
      Dilemma #39.

PMID- 11977900
TI  - Hire the Internet to manage your practice.

PMID- 11977901
TI  - Proceedings 15th Conference on Military Medicine Uniformed Services University of
      the Health Sciences.

PMID- 11977902
TI  - Pallidoreticular-rubral brain damage on magnetic resonance imaging after carbon
      monoxide poisoning.

PMID- 11977903
TI  - Relationship between absolute mean cerebral transit time and absolute mean flow
      velocity on transcranial Doppler ultrasound after ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Previous studies of transcranial Doppler (TCD) sonography
      in acute stroke have used the relative difference between the symptomatic and
      asymptomatic arteries to assess arterial occlusion. However, a simple measure of
      absolute mean flow velocity might provide a direct assessment of "perfusion
      reserve" in acute ischemic stroke. METHODS: In a prospective study, 62 patients
      with ischemic stroke had TCD and a mean cerebral transit time examination within
      48 hours of stroke. Absolute intracranial arterial mean flow velocities were
      correlated with the corresponding absolute mean transit times. RESULTS: The
      authors found a significant correlation between middle cerebral artery (MCA) mean
      flow velocity and transit time in the symptomatic (Spearman rank correlation
      coefficient [rho] = -0.65, P < .01) but not in the asymptomatic (rho = -0.04, P =
      ns) MCA territory. Equations relating absolute mean flow velocity to absolute
      transit time were derived. CONCLUSION: The findings suggest that in the normal
      hemisphere (with intact autoregulation on the horizontal portion of the
      autoregulation curve), flow velocity and transit time are not closely related to
      each other, but in the symptomatic hemisphere (on the downward slope of the
      autoregulation curve), flow velocity is directly proportional to the transit time
      and, therefore, to its inverse, perfusion reserve. The use of absolute mean flow
      velocity values on TCD should be further explored as a simple way of assessing
      "perfusion" in acute ischemic stroke.

PMID- 11977904
TI  - Regional cerebral blood flow abnormalities in nondemented patients with memory
      impairment.
AB  - BACKGROUND: Patients with objective evidence of memory impairment have been
      considered to be at risk for developing Alzheimer's disease (AD). However, little
      is known about patterns of regional cerebral blood flow abnormalities and their
      prognostic significance in these patients. METHODS: The authors retrospectively
      studied 28 nondemented subjects with memory loss and investigated patterns of
      blood flow abnormalities on single photon emission computed tomography (SPECT).
      RESULTS: The patients were followed up for more than 2 years; during follow-up,
      14 patients (50%) developed AD. The onset of memory impairment in patients who
      progressed to AD was significantly earlier than in those who remained in a
      nondemented condition. SPECT data from the initial evaluation were analyzed by
      region of interest analysis and statistical parametric mapping. Interestingly,
      both groups of patients shared hypoperfusion in the medial temporal regions and
      the posterior cingulate. In addition to these regions, significant blood flow
      reduction in the parietal and anterior cingulate cortices was detected in
      patients who progressed to AD. CONCLUSIONS: These results demonstrate that (1)
      subjects with an earlier onset of memory loss have an increased risk for
      developing AD, (2) SPECT can be useful for distinguishing subjects with memory
      loss who will rapidly progress to AD from those who will not, and (3) perfusion
      impairment typical of AD was evident even in subjects with memory impairment who
      remained nondemented.

PMID- 11977905
TI  - Intravenous tissue plasminogen activator and flow improvement in acute ischemic
      stroke patients with internal carotid artery occlusion.
AB  - BACKGROUND AND PURPOSE: It has been suggested that intravenous tissue plasminogen
      activator (TPA) would not lyse the large thrombus associated with internal
      carotid artery (ICA) occlusion and, therefore, would be ineffective in this
      setting. Vascular imaging, safety, and outcome of TPA therapy for ICA occlusion
      is not well described. Our goal was to determine the site of occlusion, early
      recanalization after TPA infusion, and its relationship to outcome. METHODS: We
      reviewed our database of all stroke patients treated with i.v. TPA between July
      1997 and July 1999. We identified all cases with carotid occlusion suggested by
      transcranial Doppler (TCD) and angiography. Occlusion and recanalization were
      assessed by site including proximal ICA (prICA), terminal ICA (tICA), and middle
      cerebral artery (MCA). Baseline National Institutes of Health Stroke Scale
      (NIHSS) scores and follow-up Rankin scores were obtained. RESULTS: We treated 20
      patients with carotid occlusion (age 63.9 +/- 10.8 years, 11 males, 9 females).
      Time to TPA infusion after stroke onset was 128 +/- 66 minutes. Baseline NIHSS
      scores were 16.4 +/- 5.4. Time to follow-up was 3.5 +/- 4.9 months (2 patients
      were lost to follow-up). Occlusion sites were prICA 40%, tICA 70%, and concurrent
      MCA 45%. Multiple sites were involved in 10/20 patients (50%). Among patients
      with pretreatment and posttreatment vascular imaging studies (n = 18),
      recanalization in the prICA and tICA was complete in 10%, partial in 16%, and
      none in 74%. MCA recanalization was complete in 35%, partial in 24%, and none in
      41%. At follow-up, Rankin 0-1 was found in 8 patients (44%), Rankin 2-3 in 3
      (17%), and Rankin 4-5 in 3 (17%). Mortality was 22% (n = 4) including 1 fatal
      intracerebral hemorrhage. Improvement was closely related to resumption of MCA
      flow (P < .01). CONCLUSIONS: Most patients did not recanalize their ICA occlusion
      after intravenous TPA therapy. However, recanalization of associated proximal MCA
      clot, found in 45% of our patients, or improved MCA collateral flow was strongly
      associated with good outcome.

PMID- 11977906
TI  - Doppler velocity criteria based on receiver operating characteristic analysis for
      the detection of threshold carotid stenoses.
AB  - BACKGROUND AND PURPOSE: Duplex scanning is an accepted method for noninvasive
      evaluation of carotid stenosis. However, the ultrasound criteria used for the
      detection of threshold stenoses vary widely between laboratories, and quality
      assurance measures to allow adjustment of criteria are often lacking. This study
      was completed using receiver operating characteristic (ROC) analysis to determine
      Doppler velocity criteria for threshold carotid stenoses, compared to an accepted
      standard, and to demonstrate methods to allow adjustment of criteria. METHODS:
      The study cohort included 134 patients who had carotid endarterectomy. Ultrasound
      and arteriographic data were collected for both the operated and nonoperated
      sides. Each carotid artery was treated as an independent case in the final
      analysis. Angiograms were used as the gold standard in ROC analysis to determine
      the Doppler velocity criteria for the detection of different threshold stenoses.
      RESULTS: The ROC analysis results showed that for the detection of 70% stenosis,
      the best Doppler systolic criterion was 200 cm/s (sensitivity 93.6%, specificity
      71.7%, area under the curve [AUC] 87.6%), the best diastolic criterion was 65
      cm/s (sensitivity 85.1%, specificity 74.6%, AUC 84.3%), and the best criterion of
      carotid ratio (CR) (internal carotid artery systolic velocity/common carotid
      artery systolic velocity) was 3.0 (sensitivity 78.7%, specificity 75.4%, AUC
      81.3%). For 50% stenosis, the best systolic criterion was 140 cm/s (sensitivity
      90.3%, specificity 95.2%, AUC 97.0%), the best diastolic criterion was 60 cm/s
      (sensitivity 98.6%, specificity 77.8%, AUC 92.1%), and the best criterion of CR
      was 2.5 (sensitivity 93.1%, specificity 72.0%, AUC 89.0%). CONCLUSIONS: This
      study showed that duplex scanning is able to detect threshold carotid stenoses.
      For the best performance, each laboratory should have its own criteria; however,
      the criteria provided here could be a helpful reference to those laboratories
      that have not yet established their own criteria. Most important, this study
      provides an example of how to evaluate the performance criteria, how to modify
      them, how such changes can affect performance, and how performance can be
      modified depending on the goals of the laboratory.

PMID- 11977907
TI  - Subclavian steal syndrome: can the blood pressure difference between arms predict
      the severity of steal?
AB  - BACKGROUND AND PURPOSE: A side-to-side difference in systolic brachial arterial
      blood pressure is a common finding in subclavian artery stenosis and is
      frequently used as a screening tool for subclavian steal syndrome (SSS). It was
      the goal of this retrospective study to investigate the relationship between
      different vertebral artery waveform types and the side-to-side difference in
      systolic blood pressure in patients with sonographically proven SSS. METHODS: The
      records of 1860 patients from the Neuroultrasound Laboratory between January 2000
      and December 2000 were screened for the diagnosis of SSS in the final ultrasound
      report. In all patients, bilateral brachial arterial blood pressure was measured
      in a sitting position prior to the ultrasound examination. Vertebral artery
      waveforms were classified as (1) systolic deceleration, (2) alternating flow, and
      (3) complete reversal at rest. Blood pressure difference as calculated by normal
      side blood pressure minus lesion-side blood pressure was compared with the 3
      Doppler waveform types. RESULTS: SSS was found in 51 of 1860 (2.7%)
      ultrasonography studies of 49 patients (17 men, 32 women; mean age 65.3 +/- 10.5
      years). Two patients (4%) had bilateral SSS. In 3 patients (6%), SSS was related
      to an innominate artery stenosis. Waveform analysis showed a completely reversed
      flow in 16 (31%), an alternating flow in 24 (47%), and a systolic deceleration in
      11 (22%) cases. Systolic blood pressure difference was significantly higher in
      the complete reversal and alternating groups than in the systolic deceleration
      group (P < .001). CONCLUSION: Brachial systolic blood pressure difference is
      related to the severity of SSS and can be used as a screening tool for SSS.
      However, it performed better in severe steal than milder steal phenomena.

PMID- 11977908
TI  - Assessment of intracranial collateral flow by transcranial color-coded duplex
      sonography using a temporal and frontal axial insonation plane.
AB  - BACKGROUND AND PURPOSE: The insonation of the posterior communicating artery
      (PcomA) is often hampered by the unfavorable insonation angle when the temporal
      acoustic bone window (TBW) is used. This problem may be ameliorated by a lateral
      frontal bone window (LFBW). This study evaluated the TBW and LFBW for the
      assessment of collateral intracranial flow conditions and aimed at defining
      diagnostic transcranial color-coded duplex sonography (TCCS) criteria that do not
      need compression maneuvers. METHODS: The A1 segment of the anterior cerebral
      artery (ACA), the PcomA, and the P1 segment of the posterior cerebral artery
      (PCA) were insonated by TCCS in 40 controls and 20 patients (16 internal carotid
      artery [ICA] occlusions or high grade stenoses, 3 middle cerebral artery stenoses
      or occlusions, 1 PCA stenosis). RESULTS: Detection rates for the A1 ACA and P1
      PCA were higher for the TBW (94%, 98%) compared to the LFBW (86%, 81%) in
      controls. The PcomA was identified more frequently through the LFBW (86%)
      compared to the TBW (80%). Through the LFBW angle, corrected flow velocity (FV)
      measurements were possible for the PcomA with an average correction of 6.5
      degrees. In controls, in > 80% of identified PcomAs, flow was directed towards
      the ICA. Side to side differences were below 7% for peak systolic FVs. In the
      patients with ICA disease, a flow reversal in the ipsilateral A1 ACA and a FV
      difference of > 30% seemed feasible for diagnosis of anterior communicating
      artery crossflow. Criteria for PcomA crossflow were side differences of FVs in
      the PcomA of > or = 30% and in the P1 PCA of > or = 20%. CONCLUSIONS: The LFBW
      proved useful as a complementary insonation plane to assess intracranial
      crossflow conditions, especially via the PcomA. We were able to define TCCS
      criteria for functional relevant collateralization without the need of
      compression maneuvers.

PMID- 11977909
TI  - Extracranial internal carotid artery occlusion: the role of common carotid artery
      volume flow.
AB  - BACKGROUND AND PURPOSE: Quantitative measurement of blood flow volume in the
      common carotid artery (CCA) is now possible using the color velocity imaging
      quantification (CVI-Q) ultrasound technique. The aim of this study was to
      evaluate the cerebral hemodynamic effects of unilateral internal carotid artery
      (ICA) occlusion on CCA blood flow volumes (FVs) using CVI-Q. METHODS: Records of
      ultrasound studies in our neurosonology laboratory were retrospectively reviewed
      to identify patients with unilateral ICA occlusions who at a minimum received
      both a routine color duplex carotid ultrasound examination and quantitative
      measurement of FV in the CCA, bilaterally, using the CVI-Q method. A total of 71
      patients met criteria and were included in the cohort. A side to side comparison
      was performed for FV, peak systolic velocities (PSV), end-diastolic velocities
      (EDV), and resistance indices (RIs) in the CCA. Results correlated with any other
      available data such as flow direction in the ophthalmic artery and the presence
      of intracranial collateralization. RESULTS: The FV, PSV, and EDV were
      significantly reduced, and the RI was significantly increased in the CCA on the
      side of the occlusion. A subgroup analysis in patients who also had an
      examination of the ophthalmic (n = 61) and the intracranial arteries of the
      Circle of Willis (n = 50), showed significantly higher FV in the CCA on the side
      of the occlusion if there was also reversed flow in the ophthalmic artery on the
      side of the occlusion (344 +/- 144 ml/min versus 169 +/- 53 ml/min). CONCLUSION:
      Quantitative FV measurement using CVI-Q ultrasound can identify clear alterations
      in volume flow, collateral pathways, and cerebral hemodynamics in patients with
      unilateral ICA occlusion. It is a complementary tool, providing additional
      objective information about the cerebral hemodynamic effects of ICA occlusion
      that goes beyond what is available using routine flow velocity data.

PMID- 11977910
TI  - Integration and added value of the modern noninvasive vascular laboratory in
      vascular diseases management.
AB  - BACKGROUND AND PURPOSE: Today's vascular laboratory technology offers broad
      applications throughout vascular medicine. We explore the diagnostic work-up and
      management of selected peripheral vascular diseases by benchmarking the
      institutional mix of invasive and noninvasive technology utilization and
      associated cost burdens. METHODS: Specialized diagnostic studies for prevention
      of stroke and pulmonary embolism, and diagnosis and management of femoral
      pseudoaneurysm were reviewed for our 355-physician clinic and hospital practice.
      The proportions and costs for invasive and noninvasive diagnostic procedures were
      tabulated for carotid stenosis, deep venous thrombosis (DVT), and iatrogenic
      femoral pseudoaneurysm. Current technology utilization mix cost burdens were
      compared to projected cost burdens for hypothetical equivalent medical value
      (i.e., the same total test volume) in the theoretical absence of noninvasive
      laboratory services. RESULTS: The technology utilization mix was dominated by
      noninvasive duplex ultrasonography for all 3 vascular disease workups. The
      technology utilization mix benchmarks were 92% noninvasive for carotid stenosis,
      98% noninvasive for DVT, and 100% noninvasive for pseudoaneurysm. Under
      hypothetical constant test volume normalized to utilization level for the 2-year
      period, the maximal range in cost burdens between current reliance on noninvasive
      diagnoses versus projected 100% reliance on invasive procedures for the 3
      vascular applications is approximately $6 million. CONCLUSION: Benchmark indices
      reveal near total adoption of noninvasive technology for vascular diagnostic
      workups at our center. The benefits to institutions of benchmarking their
      technology utilization mix and costs are discussed in relation to identifying
      potential for cost-containment from modifying technology utilization practices.

PMID- 11977911
TI  - Transcranial Doppler ultrasound: a new method of monitoring hemispheric
      anesthetization during the intracarotid amobarbital procedure.
AB  - BACKGROUND: Electroencephalography (EEG) is traditionally used to assess the
      duration of hemispheric anesthetization and to monitor return of function in the
      anesthetized hemisphere during the intracarotid amobarbital procedure (IAP), but
      EEG changes are not consistently seen. The authors evaluated the role of
      continuous transcranial Doppler (TCD) monitoring as an alternative to EEG.
      METHODS: The authors performed both continuous TCD monitoring and EEG during the
      IAP in 10 patients with medically intractable partial epilepsy. Mean velocities
      were monitored continuously in both middle cerebral arteries (MCAs), and changes
      in MCA velocities on continuous TCD monitoring were time locked with the EEG
      changes. RESULTS: The average mean MCA velocities were within normal limits
      bilaterally (50-85 cm/s) in all patients at baseline. Mean MCA velocites
      increased in all patients to 95-115 cm/s at the start of the test when the
      patients were asked to raise their hands and start counting. After injection of
      sodium amobarbital, mean MCA velocities in all patients dropped dramatically on
      the ipsilateral side to values of 12-39 cm/s and returned to the baseline average
      value when the hemiparesis recovered. In 8 patients, the duration of delta
      activity on EEG coincided with the time interval during which the mean MCA
      velocities were low on TCD monitoring. In 2 patients, despite the presence of
      hemiparesis clinically and a drop in mean MCA velocities on the ipsilateral side
      on continuous TCD monitoring, EEG remained normal on the ipsilateral side.
      CONCLUSIONS: Continuous TCD monitoring may be a more sensitive method than EEG in
      determining the duration of hemispheric anesthetization during IAP. Because the
      items for assessment of memory are presented during the period of hemispheric
      anesthetization, TCD may be useful in more precisely defining the time window for
      memory testing.

PMID- 11977912
TI  - Noninvasive ultrasound evaluation of the vertebral artery in hypertension.
AB  - BACKGROUND AND PURPOSE: Surgical decompression of the vascular loop of the
      vertebral artery (VA) at the left lateral medulla can reduce blood pressure (BP)
      in hypertension, and a larger diameter of the left VA has been found in
      hypertensive patients. Noninvasive evaluation of the VA in hypertension may
      assist selecting patients for more appropriate diagnosis and treatment. Duplex
      ultrasonography is used to study the relationship between VA diameter and BP.
      METHODS: A retrospective review of VA duplex ultrasonography was performed in 112
      consecutive patients who were sent to the neurovascular laboratory at the Wake
      Forest University School of Medicine during a 2-month period. All measurements
      (BP, pulse rate, peak systolic velocity [PSV], end diastolic velocity [EDV], and
      diameters of both VAs) were determined according to standardized protocols. Left
      right comparisons of VA diameters, PSV, and EDV between hypertensives and
      normotensives were performed by the matched-pairs analysis techniques. RESULTS:
      Fifty-five women and 57 men with a mean age of 64.8 years were studied.
      Hypertension was present in 65.2% of all patients. The age-adjusted mean left VA
      diameter was significantly higher than that of the right VA with an age-adjusted
      average differences of 0.2 mm (P = .03) for hypertensives compared to 0.04 mm (P
      = .75) for normotensives. No significant differences were observed in either PSV
      or EDV. CONCLUSIONS: Differences in left-right VA diameter in hypertensive
      subjects may be a previously unrecognized component of the vascular disturbances
      associated with the disease and represent an additional criterion for identifying
      those who may benefit from surgical and medical management.

PMID- 11977913
TI  - Magnetic resonance imaging in patients diagnosed with papilledema: a comparison
      of 6 different high-resolution T1- and T2(*)-weighted 3-dimensional and 2
      dimensional sequences.
AB  - PURPOSE: To evaluate visualization and signal characteristics of macroscopic
      changes in patients with ophthalmologically stated papilledema and to find a
      suitable high-resolution magnetic resonance imaging (MRI) protocol. METHOD: Nine
      consecutive patients with 12 ophthalmologically stated papilledemas underwent MRI
      of the head and orbits, which consisted of the following high-resolution
      sequences: 3-dimensional (3D), T2*-weighted (T2*w) constructive interference in
      steady-state sequence (CISS); 3D, T1-weighted (T1w) magnetization prepared-rapid
      gradient echo sequence (MP-RAGE) (with and without intravenous contrast medium);
      transverse 3D and 2-dimensional (2D) (2 mm), T2-weighted (T2w) turbo spin echo
      (TSE); transverse 2D (2 mm), contrast-enhanced T1w TSE with fat-suppression
      technique; and transverse 2D (5 mm), T2w TSE. A quantitative and qualitative
      evaluation of the papilla, optic nerve, optic nerve sheath, optic chiasm, and the
      brain was performed. The 6 high-resolution sequences were compared. RESULTS: The
      elevation of the optic disc into the optic globe in ophthalmologically stated
      papilledema was best visualized in T2w, 3D CISS sequence. The pathological
      contrast enhancement was best seen in T1w contrast-enhanced 2D TSE sequence with
      fat-suppression technique. The mean width of the optic nerve sheath directly
      behind the globe was 7.54 mm (+/- 1.05 mm) in the pathological eyes, compared to
      5.52 mm (+/- 1.11 mm) in the normal eyes. In all patients, the cerebral indices
      calculated showed no signs of increased intracranial pressure or other
      abnormalities changing the volume of the brain or ventricles. The contrast of the
      orbital fat versus the optic nerve sheath, the optic nerve sheath versus the
      surrounding cerebrospinal fluid (CSF), the surrounding CSF versus the optic
      nerve, the optic chiasm versus the CSF, and the optic papilla versus the optic
      globe were best visualized in the 3D, T2*w CISS sequence. An enhancement of the
      swollen optic nerve head was best seen in all 12 cases in the T1w contrast
      enhanced 2D TSE sequence with fat-suppression technique. CONCLUSION: An MRI
      protocol consisting of a 5-mm transverse T2w TSE sequence; a T2*w, 3D CISS
      sequence; a T1w, 3D MP-RAGE sequence with and without contrast medium; and a
      transverse T1w, (2-mm) 2D TSE sequence with fat-suppression technique with
      intravenous contrast medium is suitable to visualize the macroscopic changes in
      papilledema. In addition, this combination is an excellent technique for the
      examination of the orbits and the brain.

PMID- 11977914
TI  - Activation of pre-supplementary motor area (SMA) and SMA proper during unimanual
      and bimanual complex sequences: an analysis using functional magnetic resonance
      imaging.
AB  - Several functional imaging studies have shown that the extent of activation and
      percentage change in cerebral blood flow in the supplementary motor area (SMA)
      during a bimanual mirror performance of a simple repetitive movement are almost
      identical to those during a unimanual movement. The aim of this study was to
      investigate whether this finding was also applicable to a more complex movement.
      Eight right-handed, healthy volunteers performed unimanually (with their right
      and left hands) and bimanually (in a mirror fashion) thumb-finger opposition in a
      nonconsecutive order (index-middle-index-ring-index-little-index-middle ...
      fingers). The SMA proper was more activated during the bimanual movement than the
      unimanual movement with either hand. This is in accordance with the hypothesis
      that bimanual movement, even in a mirror fashion, is more difficult than
      unimanual movement when the task is complex but not when the task is simple. Pre
      SMA was inconsistently activated. The results suggest that the SMA proper plays
      an active role in executive processing during bimanual mirror performance of
      complex movements.

PMID- 11977915
TI  - Vertebral artery dissection presenting with isolated neck pain.
AB  - Unilateral pain in the cervical region and limitation of neck movements are
      nonspecific symptoms frequently encountered in daily medical practice. Vertebral
      artery dissection is rarely considered as a diagnostic possibility unless
      brainstem or cerebellar ischemia follows the acute pain. Three cases of vertebral
      artery dissection (VAD) having the sole complaint of pain of acute onset in the
      posterior neck region are presented. None of the patients had ever reported a
      similar pain, and the neurological examination was unremarkable in all of them.
      Doppler ultrasonography suggested VAD in 2 cases, and the diagnosis was confirmed
      with T1 fat-suppressed magnetic resonance imaging technique in all patients.
      Severe neck pain and/or occipital headache frequently accompanies ischemic
      symptoms in cases with VAD. The cases in this report emphasize that spontaneous
      and often unilateral posterior cervical pain of acute onset can be the only
      manifestation of a VAD. A high degree of suspicion especially in young patients
      with no past history of a similar pain can help to establish the diagnosis,
      thereby preventing erroneous and potentially hazardous therapeutic interventions
      such as physiotherapy or neck manipulation.

PMID- 11977916
TI  - Magnetic resonance imaging of primary spinal intramedullary lymphoma.
AB  - The authors report 2 cases of primary spinal intramedullary lymphoma and review
      all previously reported magnetic resonance imaging findings on this disease. The
      most common finding was a solid and homogeneously enhanced mass that was
      hyperintense on T2-weighted images, without associated syringomyelia. In a few
      cases, swelling of the spinal cord was minimal.

PMID- 11977917
TI  - Meningitis complicating an occult infected nasal epidermoid cyst in a child.
AB  - Congenital nasal epidermoid cyst without associated facial dysmorphism is an
      uncommon anomaly that is often asymptomatic. We report a case of occult nasal
      epidermoid cyst in a 12-year-old boy with initial nonspecific symptoms of fever,
      headache, abdominal pain, vomiting, and diarrhea. An enhanced magnetic resonance
      imaging (MRI) showed a cystic lesion in the frontal skull base with expansion of
      the foramen cecum and the perpendicular plate of the ethmoid bone, accompanied
      with meningitis. An emergent surgical intervention was undertaken, and an
      infected epidermoid cyst was confirmed by pathology. He recovered uneventfully
      during a 4-week treatment with parentally-administered antibiotics. This
      significant case report demonstrates the importance of MRI in the early diagnosis
      of a life-threatening intracranial infection from an otherwise occult infected
      congenital nasal epidermoid cyst in children.

PMID- 11977918
TI  - Subclavian steal and a persistent trigeminal artery.
AB  - A persistent trigeminal artery (PTA) has been found in a number of
      cerebrovascular diseases. A 73-year-old asymptomatic woman was noted to have a
      left PTA and left subclavian steal by catheter angiography. Carotid duplex
      revealed a peak systolic flow velocity of 294 cm/s in the internal carotid artery
      (ICA) and an ICA to common carotid artery ratio > 4, suggestive of a high-grade
      stenosis. Only a low-grade stenosis was identified by catheter angiography. The
      elevated flow velocities in the left ICA were attributed to increased collateral
      blood flow across the stenosis to the left PTA, which compensated for the
      subclavian steal. Transcranial Doppler found an alternating flow pattern in the
      basilar artery (mean flow velocity [MFV] = 18 cm/s) and left vertebral artery
      (MFV = 43 cm/s). During brachial hyperemia, the MFV increased by 178% in the
      basilar artery and 102% in the left vertebral artery. The data suggest that a PTA
      may compensate for subclavian steal and may have a protective hemodynamic role in
      this setting.

PMID- 11977919
TI  - [Post-marketing surveillance of antibacterial activities of cefozopran against
      various clinical isolates--I. Gram-positive bacteria].
AB  - As a post-marketing surveillance, the in vitro antibacterial activities of
      cefozopran (CZOP), an agent of cephems, against various clinical isolates were
      yearly evaluated and compared with those of other cephems, oxacephems,
      penicillins, and carbapenems. Changes in the bacterial sensitivity for CZOP were
      also evaluated with the resistance ratio calculated with breakpoint MIC. Sixteen
      species (1,913 strains) of Gram-positive bacteria were isolated from the clinical
      materials annually collected from 1996 to 2000, and consisted of methicillin
      susceptible Staphylococcus aureus (MSSA; n = 178), methicillin-resistant S.
      aureus (MRSA; n = 199), methicillin-susceptible Staphylococcus epidermidis (MSSE;
      n = 98), methicillin-resistant S. epidermidis (MRSE; n = 164), Staphylococcus
      haemolyticus (n = 72), Staphylococcus saprophyticus (n = 28), Enterococcus
      faecalis (n = 206), Enterococcus faecium (n = 91), Enterococcus avium (n = 72),
      Streptococcus pyogenes (n = 133), Streptococcus agalactiae (n = 138), penicillin
      susceptible Streptococcus pneumoniae (PSSP; n = 133), penicillin-intermediate
      resistant S. pneumoniae (PISP; n = 100), penicillin-resistant S. pneumoniae
      (PRSP; n = 29), Streptococcus milleri group (n = 135) and Peptostreptococcus spp.
      (n = 137). CZOP possessed comparable antibacterial activities against MSSA and
      MSSE to other cephems, and was also effective on MRSE but not on MRSA. An
      antibacterial activity of CZOP against S. saprophyticus was comparable to or
      higher than other cephems. CZOP, however, did not indicate an antibacterial
      activity against S. haemolyticus, just like other cephems. An antibacterial
      activity of CZOP against E. faecalis was comparable to cefpirome (CPR) and higher
      than other cephems. No antibacterial activity of CZOP against E. faecium and E.
      avium was observed, just like other drugs. An antibacterial activity of CZOP
      against S. pyogenes was as potent as that of cefotiam (CTM), cefepime (CFPM) and
      CPR, and that against S. agalactiae was also preferable. CZOP and other cephems
      also had a preferable antibacterial activity against S. milleri group that was
      most sensitive to benzylpenicillin. An antibacterial activity of CZOP against
      Peptostreptococcus spp. was preferable but weaker than that of cefazolin, CTM and
      cefmetazole. The resistance ratio estimated with breakpoint MIC of CZOP was 96.5%
      in MRSA, 93.1% in PRSP, 60.0% in PISP, 40.3% in S. haemolyticus, 22.3% in E.
      faecalis, and 15.9% in MRSE. Those resistance ratios were similar to those for
      CFPM, but E. faecalis showed 90.8% resistance for CFPM. The difference in the
      resistance ratio of E. faecalis demonstrated that CZOP successfully maintained
      its antibacterial activity against this species. In conclusion, no remarkable
      annual change in the antibacterial activities of CZOP against the Gram-positive
      bacteria was observed. The sensitivities of PISP and PRSP to CZOP, however, was
      suggested to be decreasing.

PMID- 11977920
TI  - [Post-marketing surveillance of antibacterial activities of cefozopran against
      various clinical isolates--II. Gram-negative bacteria].
AB  - As a post-marketing surveillance, the in vitro antibacterial activities of
      cefozopran (CZOP), an agent of cephems, against various clinical isolates were
      yearly evaluated and compared with those of other cephems, oxacephems,
      penicillins, monobactams, and carbapenems. Changes in CZOP susceptibility for the
      bacteria were also evaluated with the bacterial resistance ratio calculated with
      the breakpoint MIC. Twenty-five species (3,362 strains) of Gram-negative bacteria
      were isolated from the clinical materials annually collected from 1996 to 2000,
      and consisted of Moraxella (Branhamella) catarrhalis (n = 136), Haemophilus
      influenzae (n = 289), Escherichia coli (n = 276), Klebsiella pneumoniae (n =
      192), Klebsiella oxytoca (n = 157), Enterobacter cloacae (n = 189), Enterobacter
      aerogenes (n = 93), Serratia marcescens (n = 172), Serratia liquefaciens (n =
      24), Citrobacter freundii (n = 177), Citrobacter koseri (n = 70), Proteus
      mirabilis (n = 113), Proteus vulgaris (n = 89), Morganella morganii (n = 116),
      Providencia spp. (n = 41), Pseudomonas aeruginosa (n = 290), Pseudomonas
      fluorescens (n = 56), Pseudomonas putida (n = 63), Acinetobacter baumannii (n =
      146), Acinetobacter lwoffii (n = 34), Burkholderia cepacia (n = 101),
      Stenotrophomonas maltophilia (n = 169), Bacteroides fragilis group (n = 196), and
      Prevotella/Porphyromonas (n = 173). An antibacterial activity of CZOP against E.
      coli, K. pneumoniae, K. oxytoca, and S. marcescens was potent and consistent with
      or more preferable than the study results obtained until the new drug application
      approval. MIC90 of CZOP against M.(B.) catarrhalis, C. koseri, and P. aeruginosa
      was not considerably changed and consistent with the study results obtained until
      the new drug application approval. MIC90 of CZOP against E. cloacae, E.
      aerogenes, and P. mirabilis increased year by year. The increase in MIC90 of CZOP
      against E. aerogenes and P. mirabilis, however, was not considered to be an
      obvious decline in susceptibility. In contract, the susceptibility of E. cloacae
      to CZOP was suspected to be decreasing because this species showed 20.6%
      resistance to CZOP. MIC90 of CZOP against C. freundii was variably changed or not
      one-sidedly, but was higher than the values obtained until the new drug
      application approval. Additionally, MIC90 of CZOP against H. influenzae was
      stable during 5 years except being higher in 1999, and, as a whole, was a little
      higher than the values obtained until the new drug application approval. An
      antibacterial activity of CZOP against P. fluorescens, P. putida, B. cepacia, S.
      maltophilia, B. fragilis group, and Prevotella/Porphyromonas was weak like the
      other cephems. Changes in MIC90 of CZOP against the other bacteria were 2 tubes
      or more through 5-year study period, but did not tend towards a unilateral
      direction as meaning a decline in susceptibility.

PMID- 11977921
TI  - [In vitro interaction of tazobactam/piperacillin combined with aminoglycosides
      against Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli AND
      Staphylococcus aureus].
AB  - The in vitro combination effect of tazobactam/piperacillin (TAZ/PIPC) with
      aminoglycosides (amikacin (AMK) and isepamicin (ISP)) were investigated by the
      checkerboard dilution method against PIPC-resistant and TAZ/PIPC-susceptible
      Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Methicillin
      sensitive Staphylococcus aureus (MSSA). The following results were obtained. 1.
      The combination of TAZ/PIPC with AMK showed synergistic effect for 66.7% of P.
      aeruginosa and 9.1% of K. pneumoniae and additive effect for 76.9% of E. coli and
      74.1% of MSSA. The antagonistic effect of TAZ/PIPC with AMK was not demonstrated
      for all tested strains. 2. The combination of TAZ/PIPC with ISP showed
      synergistic effect for 61.9% of P. aeruginosa and 22.7% of K. pneumoniae and
      additive effect for 84.6% of E. coli and 66.7% of MSSA. The antagonistic effect
      of TAZ/PIPC with ISP was not demonstrated for all tested strains. In conclusion,
      these results suggest that the combination therapies of TAZ/PIPC with
      aminoglycosides are useful for the clinical treatment of sepsis caused by above
      four species.

PMID- 11977922
TI  - [Bactericidal activity of biapenem against various efflux system mutants of
      Pseudomonas aeruginosa].
AB  - The bactericidal activity of biapenem, a new carbapenem, against various efflux
      mutants of Pseudomonas aeruginosa was compared with those of imipenem, panipenem,
      meropenem and ceftazidime. The bactericidal activity of biapenem against P.
      aeruginosa KG5001, a strain deficient in MexAB-OprM, MexCD-OprJ and MexXY-OprM,
      was very strong compared with those of imipenem and meropenem. In terms of
      bactericidal activities, biapenem and imipenem had similar activities against P.
      aeruginosa KG5003, a strain overexpressing MexAB-OprM, as against P. aeruginosa
      KG5001, however meropenem and ceftazidime had weaker activities against KG5003
      than KG5001. The bactericidal activity against P. aeruginosa KG5007, a strain
      overexpressing MexCD-OprJ, was observed only by biapenem. The bactericidal
      activity of biapenem was strong and not influenced by all of these three efflux
      systems.

PMID- 11977923
TI  - [Pharmacokinetic study of penetration of meropenem into pleural effusion in
      patients with pleurisy].
AB  - Complication by secondary infection is observed in not only bacterial pleurisy
      but also other pleurisy, and the appropriate administration of antibacterial
      agents is necessary. It is very important to secure a smooth penetration of
      systemically administered antibacterial agents to pleural effusion in infection
      therapy. In this study, we investigated the pharmacokinetics of a carbapenem
      antibiotic, meropenem (MEPM), in blood and pleural effusion in patients with an
      accumulation of pleural effusion caused by pleurisy, who underwent placement of
      an indwelling thoracic drain and received intravenous drip administration of MEPM
      for pneumonia or other respiratory tract infection. The blood pharmacokinetic
      parameters of MEPM after an intravenous drip administration of 0.5 g MEPM in six
      patients were: area under the blood concentration-time curve (AUCx), 37.9 +/- 6.2
      (hr.mg/L); volume of distribution (Vd), 27.3 +/- 4.4 (L); total clearance
      (CLtotal), 13.4 +/- 1.8 (L/hr); elimination half life (t1/2), 0.50 +/- 0.08 (hr
      1); and elimination rate constant (kel), 1.42 +/- 0.22 (hr). The pharmacokinetic
      parameters in pleural effusion were: AUCx, 35.7 +/- 7.1 (hr.mg/L); mean retention
      time (MRT), 5.00 +/- 3.25 (hr); variance of retention time (VRT), 29.9 +/- 44.6
      (hr2); kel, 0.34 +/- 0.27 (hr-1); and t1/2, 3.14 +/- 2.36 (hr). The penetration
      rate calculated from the ratio of pleural concentration to blood concentration in
      each patient was 46.5 +/- 26.1%, showing good penetration comparable or superior
      to those of other antibacterial agents previously reported. From these results,
      it was suggested that MEPM was rapidly penetrated to the pleural effusion and was
      retained for a more prolonged time in the pleural effusion than in the blood of
      patients with accumulated pleural effusion, and it suggested the usefulness of
      MEPM in antibacterial therapy for patients with pleurisy causing accumulation of
      pleural effusion.

PMID- 11977925
TI  - Nutrient absorption and intestinal adaptation with ageing.
AB  - Malabsorption of carbohydrates, lipids, amino acids, minerals and vitamins has
      been described in the elderly. The ability of the intestine to adapt may be
      impaired in the elderly and this may lead to further malnutrition. Dietary
      manipulation may prove to be useful to enhance the needed intestinal absorption
      with ageing. There is an age-associated increase in the prevalence of
      dyslipidaemia as well as diabetes. These conditions may benefit from nutritional
      intervention targeted at reducing the absorption of some nutrients. With the
      continued characterization of the proteins involved in sterol and fatty acid
      absorption, therapeutic interventions to modify absorption may become available
      in the future.

PMID- 11977926
TI  - Small bowel disease in the elderly: diarrhoea and malabsorption.
AB  - Diarrhoea and malabsorption are common problems in elderly persons. Worldwide,
      diarrhoea is the second leading cause of mortality. In the developed world, 85%
      of its mortality affects the elderly. The diagnostic work up for diarrhoea and
      malabsorption is more complex for the elderly than for the young patient. If
      diarrhoea persists for more than 24 h, oral rehydration solutions or intravenous
      fluids must be administered promptly in order to prevent hypotension and organ
      failure in the often multi-morbid patient. Both the immunocompromised patient and
      the severely affected out-patient should have stool culture performed.
      Malabsorption usually presents with weight loss, osteoporosis, anaemia, skin and
      neurological symptoms. The careful diagnostic work-up must aim at the
      identification of treatable disorders such as coeliac disease, Crohn's disease
      and bacterial overgrowth. Often, a detailed drug history is of help in
      identifying a readily treatable cause.

PMID- 11977927
TI  - Coeliac disease.
AB  - Increased awareness of non-classical presentations and more reliable screening
      tests have led to higher detection rates for coeliac disease in elderly adults.
      Clinical presentations are influenced largely by the long-standing course of the
      subclinical disease before diagnosis. In the majority of elderly patients, weight
      loss, diarrhoea and iron deficiency anaemia are present. With a delay in
      diagnosis, there are increased risks of associated autoimmune diseases, of
      neoplasms (mostly small bowel lymphoma) and of metabolic bone diseases. Thyroid
      disease is the most common autoimmune disease. Lymphoma may be the initial
      presentation or may complicate the clinical course of well established coeliac
      disease. Osteopenia is very common at presentation, can be clinically severe and
      require specific therapy in addition to the gluten-free diet. The high risk of
      complications in elderly patients with coeliac disease warrants a systematic
      approach in their investigation and management.

PMID- 11977928
TI  - Ischaemic colitis.
AB  - The term colonic ischaemia was first coined approximately 40 years ago. Up until
      that point, the disease was only diagnosed in cases where the colon was
      completely gangrenous. In the 1960s reversible non-transmural ischaemia of the
      colon was described and much has been written about the disease since. Ischaemic
      colitis is usually a disease process that is seen in the elderly. However, the
      true incidence of the disease remains unknown since many cases are probably never
      diagnosed. We now know that the disease can occur both with occlusive and non
      occlusive vascular disease, the latter being much more common. Although factors
      that contribute to non-occlusive disease have been identified, often the exact
      pathophysiology is unclear and this is an area where further research is needed.
      Known facts about the pathophysiology and aetiology of the disease will be
      discussed in this chapter. The key to diagnosis is often a high degree of
      clinical suspicion. Various diagnostic modalities are described, but colonoscopy
      remains the main instrument of accurate diagnosis. Fortunately the majority of
      patients will have self-limiting disease and, accordingly, they usually respond
      to conservative therapy. When the disease progresses to transmural infarction,
      surgery is required and the prognosis is guarded. Since many of the patients are
      elderly with other underlying diseases, it is unlikely that major treatment
      advances will allow us to significantly alter the prognosis in this group of
      patients with transmural ischaemia.

PMID- 11977929
TI  - Irritable bowel syndrome in the elderly.
AB  - Irritable bowel syndrome (IBS) is a highly prevalent and frequently lifelong
      gastrointestinal disorder, but whether advancing age impacts on IBS is largely
      unknown and how the disorder manifests in the elderly remains unclear.
      Epidemiological studies suggest that the prevalence of IBS declines with age
      (possibly related to pain perception changes), but IBS remains a common
      gastrointestinal illness in the aged. Unfortunately, there has been very little
      research examining risk factors, diagnosis and treatment of IBS in the elderly.
      Since gastrointestinal cancer increases with age, diagnostic algorithms differ in
      the elderly. There is reason to believe that this very prevalent disorder may
      also behave differently in the elderly and that the approach to management needs
      to take age-related issues into account. These issues will be the focus of the
      present review.

PMID- 11977930
TI  - Inflammatory bowel disease.
AB  - Although inflammatory bowel disease (IBD) usually presents in adolescents and
      young adults, both ulcerative colitis and Crohn's disease can also present in
      older adults. The diagnosis of IBD in the elderly is often difficult and can
      easily be confused with diverticulitis or ischaemic colitis. The symptoms and
      complications of IBD in the elderly are similar to those found in younger
      patients. However, when IBD presents later in life the disease is often less
      extensive and milder. Older IBD patients are treated with the same medications as
      younger patients, although the risk for drug toxicity is greater, especially with
      corticosteroid therapy. Comorbid illness in older patients often has a
      significant impact on the outcome of medical and surgical therapy for IBD but, in
      the absence of significant co-morbid disease, most elderly IBD patients can
      expect a good response to therapy.

PMID- 11977931
TI  - Colonic cancer and polyps.
AB  - Colorectal cancer (CRC) is one of the best studied cancers. It is easily
      accessible and develops slowly over several years from premalignant lesions
      (adenomatous polyps) to invasive cancers. The key molecular events in this
      sequence have been characterized. Different screening strategies have proven to
      be effective in lowering both the mortality and the incidence of CRC.
      Nevertheless, CRC is still the second leading cause of cancer-related deaths for
      both men and women in the USA and other Western countries. An estimated 130 000
      new cases and more than 50 000 deaths have been diagnosed in the USA in 2000.
      Surgical resection remains the only curative treatment, and the likelihood of
      cure is greater when the disease is detected at an early stage. Hereditary non
      polyposis colorectal cancer (HNPCC) and the different polyposis syndromes such as
      familial adenomatous polyposis (FAP) or Peutz-Jeghers disease are rare causes of
      CRC but have been a major focus of research in past years, helping with the
      understanding of the molecular events in carcinogenesis. This review summarizes
      our current knowledge of the pathogenesis and management of colorectal polyps and
      polyposis syndromes as well as sporadic CRC.

PMID- 11977932
TI  - General geriatrics and gastroenterology: constipation and faecal incontinence.
AB  - The incidence of constipation increases with age but no consistent changes of
      colonic or anorectal motility have been shown in elderly people. Instead,
      neurological diseases, constipating drugs, bedriddenness and weak straining
      ability may explain this increased prevalence of constipation. The amount of
      dietary fibre in the diet may be reduced because of poor chewing ability.
      Parkinson's disease is accompanied by both slow colonic transit and impaired
      relaxation of the anal sphincter. Drug-induced constipation is particularly
      likely with anti-parkinsonism drugs (either anti-cholinergic or dopaminergic) and
      also with tricyclic anti-depressants, opiates, iron, anti-convulsants and
      aluminium- or calcium-containing antacids. The prevalence of faecal incontinence
      is also increased in elderly people. About half of frail bedridden
      institutionalized patients are incontinent. Anal sphincter pressures tend to be
      lower, but variables of sensitivity are not. In bedridden people faecal impaction
      may occur. The ensuing rectal distension leads to relaxation of the internal
      sphincter and hence to faecal soiling. The condition is often overlooked though
      correct diagnosis is rather simple, being made with a digital rectal examination.

PMID- 11977933
TI  - Diverticular disease.
AB  - Diverticular disease is a common finding in Western countries with an increasing
      prevalence with age. Many patients with the disorder remain asymptomatic.
      However, up to 30% of those affected may show clinical signs including pain,
      bleeding, obstruction, abscess, fistulae and perforation. The purpose of this
      chapter is to review the epidemiology, pathogenesis, clinical presentation,
      diagnostic regimens and treatment options for this disorder.

PMID- 11977934
TI  - Liver disease in the elderly.
AB  - Ageing of the liver mainly affects the sinusoids and the Kupffer cells.
      Pseudocapillarization, manifested by reduced sinusoidal fenestration and
      subendothelial collagen deposition, causes a reduction in oxygen-dependent
      hepatocyte functions such as oxidative drug metabolism. The liver mass in old
      people is somewhat reduced and the liver blood flow is diminished. This causes a
      reduction in the clearance of rapidly cleared drugs, but the clearance of slowly
      cleared drugs is not affected. The overall capacity of the liver to regenerate is
      maintained in old people. Therefore, hepatic resections for hepatocellular
      carcinoma can be carried out in non-cirrhotic elderly people. For liver
      transplantations, biological age is more important than calendar age.
      Transplantations in frail old people and in elderly people with very poor liver
      function are associated with increased morbidity and limited survival. In
      relatively healthy old people, the results are as good as those in younger age
      groups. An increased prevalence of hepatitis C associated cirrhosis and
      hepatocellular carcinoma in the elderly population is to be expected, at least in
      the next 20 years. There is a high prevalence of gallstones among old people, in
      particular among females. For symptomatic choledocholithiasis in elderly
      patients, endoscopic bile duct clearance does not necessarily need to be followed
      by cholecystectomy.

PMID- 11977935
TI  - Pancreatic disease in the elderly.
AB  - Pancreatic diseases occur in patients of every age. Older individuals suffer more
      often from gallstone related acute pancreatitis, ischaemic and idiopathic acute
      pancreatitis, whereas alcohol-induced acute pancreatitis occurs only in a
      minority of cases. Similarly, alcohol-related chronic pancreatitis in elderly
      people is rare and late-onset idiopathic chronic pancreatitis is the most common
      form of the disease. This form of chronic pancreatitis is characterized by faster
      progression to endocrine and exocrine pancreatic insufficiency and less severe
      pain compared to the clinical picture found in younger patients. Ductal
      pancreatic adenocarcinomas, which are responsible for more than 90% of exocrine
      pancreatic tumours, are typically a disease of the elderly patient. Today
      pancreatic resection still offers the only hope for cure and also can be
      performed safely in elderly patients. Age, by itself, is not a reason for
      withholding surgical intervention from an individual patient. Today, denial of
      pancreatic resection is much more likely to be based on severe co-morbidity.

PMID- 11977937
TI  - Preface.

PMID- 11977938
TI  - Should fine needle aspiration cytology in breast assessment be abandoned?
AB  - Fine needle aspiration cytology (FNAC) has been used extensively in the U.K. for
      the diagnosis of breast lesions over the past 15 years. More recently, large
      gauge needle biopsy has been used to address many of the problems which have been
      encountered with fine needle aspiration. This paper reviews the evolution of the
      use of these procedures and the advantages and disadvantages of each. In
      considering whether to abandon the use of fine needle aspiration cytology in
      breast assessment, each individual unit should make a decision based upon their
      own audited results. However, even if FNAC is retained, it is important to be
      able to complement cytological diagnosis with core biopsy as there are
      indisputable advantages, e.g. in the diagnosis of mammographically detected
      microcalcification. As always, a multi-disciplinary approach is ultimately
      essential for effective patient management.

PMID- 11977939
TI  - von Hippel-Lindau disease: MRI of abdominal manifestations.
AB  - The cranial and spinal manifestations of von Hippel-Lindau disease are well
      known. Less attention has been given to the varied abdominal manifestations. We
      present a pictorial review of the cystic and solid tumours involving the kidneys,
      pancreas and adrenal glands as demonstrated by magnetic resonance imaging. We
      highlight the advantages of this non-ionizing technique in the assessment of this
      young group of patients with a protracted screening future.

PMID- 11977940
TI  - Craniosynostosis.
AB  - Craniosynostosis, caused by premature fusion of the sutures, may be syndromic or
      non-syndromic. Radiology has an important role to play in the assessment,
      management and follow-up of these patients. Initial investigations may often be
      undertaken within general radiology departments. An understanding of the
      terminology and recognition of the predictable patterns of presentation are
      essential to enable appropriate referral to a craniofacial unit where further
      investigation and management are undertaken. We present the radiological features
      of several craniosynostoses with an emphasis on the role of plain radiography. We
      demonstrate the complementary role of computed tomography in their evaluation
      within the setting of a specialist centre.

PMID- 11977941
TI  - The atlanto-axial joint: physiological range of rotation on MRI and CT.
AB  - AIMS: To measure the range of rotation and determine the instantaneous axis of
      rotation of the atlanto-axial joint in healthy volunteers using magnetic
      resonance imaging (MRI) and to highlight the appearances of the rotated atlanto
      axial joint on computed tomography (CT) and MRI. MATERIALS AND METHODS: Twenty
      eight healthy volunteers were examined using MRI during maximal head rotation. In
      addition, an anatomical specimen of the atlanto-axial joint, fixed in varying
      degrees of rotation, was imaged using CT. RESULTS: At the extremes of
      physiological rotation in healthy subjects there is striking but incomplete loss
      of contact between the articular surfaces of the atlas (C1) and the axis (C2).
      The range of rotation to the right was 20-48.5 degrees (mean 32.4 degrees ) and
      to the left was 13-52.75 degrees (mean 34.2 degrees ). There was no significant
      difference between rotation to the right and left (P = 0.455). Total rotation was
      45-88.5 degrees (mean 69.25 degrees ). The instantaneous axis of rotation was
      located within the odontoid peg. CONCLUSION: There is a wide range of atlanto
      axial rotation in normal subjects. The instantaneous axis of rotation lies within
      the odontoid peg. The appearances of the rotated atlanto-axial joint are striking
      and may be misinterpreted as subluxation.

PMID- 11977942
TI  - MR imaging of recurrent head and neck tumours following flap reconstructive
      surgery.
AB  - AIM: The purpose of this study was to evaluate the magnetic resonance imaging
      (MRI) characteristics of recurrent tumours in patients who had undergone
      resection of primary head and neck tumours with flap reconstruction. MATERIALS
      AND METHODS: MR examinations obtained from 25 patients who had undergone
      resection and flap reconstructive surgery for malignancy were analysed
      retrospectively. Tumour recurrence was confirmed by biopsy in 22 patients, and
      clinically in 3 patients. The features of the recurrent tumours in the scars were
      reviewed. RESULTS: Twenty-one patients had a locally recurrent mass, while 4 had
      a locally recurrent mass in addition to regional lymph node metastases. Twenty
      four of the recurrent tumours were localized in the recipient flap beds, near the
      anastomotic site. In 9 of 25 (36%) patients, the recurrent tumours extended
      intracranially, either directly, or through the foramina at the skull base.
      CONCLUSION: Tumour recurrence after flap reconstruction most often occurred at or
      near the anastomotic site. MRI is useful for detection of recurrence after flap
      reconstructive surgery in patients with head and neck cancer.

PMID- 11977943
TI  - Sub-aponeurotic fluid collections in infancy.
AB  - AIM: To describe the radiological features and natural history of sub-aponeurotic
      fluid collections presenting after the neonatal period. MATERIALS AND METHODS:
      All cases of sub-aponeurotic scalp fluid collection presenting to the radiology
      department between June 1996 and June 2000 were reviewed. Note was made of the
      birth history, the radiographic and ultrasound features and the natural history
      (including any treatment) of the collection. RESULTS: Seven cases of sub
      aponeurotic fluid collections were identified. There were six infants who
      presented 3.5-18 weeks (mean nine weeks) after delivery, four of whom had had
      ventouse-assisted delivery. The last case was in a seven-year-old child who
      presented one month after minor head trauma. Clinical examination revealed non
      tender, soft, mobile and fluctuant scalp swellings in all patients. Ultrasound
      identified sonolucent fluid collections of between 5 and 24 mm depth in the sub
      aponeurotic space. No skull fractures were identified. Six patients were treated
      conservatively and one had fluid aspirated and a compression bandage applied. All
      cases resolved 2-24 weeks after diagnosis and there were no long-term sequelae.
      CONCLUSION: Sub-aponeurotic scalp collections presenting after the neonatal
      period are usually associated with ventouse-assisted delivery ultrasound is
      useful for diagnosis. The condition is benign and resolution occurs with
      conservative treatment.

PMID- 11977944
TI  - The radiographic appearances of non-specific small intestinal ulceration.
AB  - AIM: To determine the imaging characteristics of non-specific ulceration of the
      small intestine. MATERIALS AND METHODS: The radiographic investigations
      undertaken in three patients originally referred for visceral angiography in whom
      a histological diagnosis of non-specific ulceration of the small bowel was
      subsequently made were retrospectively reviewed. Two men and one woman aged from
      17 to 24 years all presented with anaemia requiring blood transfusion. Visceral
      angiography was available for review in all three patients, abdominal computed
      tomography in two, and a small bowel enema and white cell scintigraphy in one.
      RESULTS: In all three patients an angiographic abnormality was present within the
      ileum consisting of irregularity of the vasa recta, an area of subtle increased
      vascularity and early venous return. A long, non-branching vessel interpreted as
      a persistent vitello-intestinal artery was seen in two of these patients. A CT
      abnormality was present in two individuals consisting of a focal area of
      thickened small bowel. The single small bowel enema demonstrated a focal
      stricture and the white cell scan showed localized accumulation of radioactivity
      within the pelvis. CONCLUSION: Non-specific small intestinal ulceration may
      produce abnormalities that are discernible on barium studies, computed
      tomography, radiolabelled white cell scanning and visceral angiography.
      Recognition of these findings may allow a pre-operative diagnosis of this
      condition.

PMID- 11977945
TI  - Assessment of radiological referral practice and effect of computer-based
      guidelines on radiological requests in two emergency departments.
AB  - AIM: To assess medical emergency radiology referral practice compared with a set
      of French guidelines and to measure the efficiency of computer-based guidelines
      on unnecessary medical imaging. MATERIALS AND METHODS: All radiological requests
      were computerized in the medical emergency departments of two French teaching
      hospitals. During control periods, radiological requests were recorded but no
      action was taken. During intervention periods, reminder displays on screen
      indicated the appropriate recommendations. Three control and three intervention
      periods of 1 month each were conducted. The percentage of requests that did not
      conform to the guidelines and variation related to periods of control and
      intervention were measured. RESULTS: The proportion of requests that did not
      conform to the guidelines was 33.2% when the guidelines were inactive and
      decreased to 26.9% when the recommendations were active (P < 0.0001). The three
      imaging examinations (chest radiographs, abdominal plain radiographs and CT of
      the brain) accounted for more than 80% of all requests; more than 50% of
      abdominal plain radiographs requests did not conform with recommendations while
      this percentage was respectively 24.9% and 15.8% for chest radiographs and
      computed tomography (CT) of the brain. Seven situations accounted for 70% of non
      conforming radiological referrals; in these situations, junior practitioners'
      knowledge was inadequate. CONCLUSION: While the computer provided advice that was
      tailored to the needs of individual patients, concurrent with care, the effect of
      our intervention was weak. However, our study identified the few situations that
      were responsible for the majority of unnecessary radiological requests; we expect
      that this result could help clinicians and radiologists to develop more specific
      actions for these situations.

PMID- 11977946
TI  - Cost-effectiveness of barium enemas performed by radiographers.
AB  - AIM: To assess the cost-effectiveness of barium enemas performed by radiographers
      compared to those performed by consultant radiologists. METHOD: Prospective study
      of 200 barium enemas carried out by a senior radiographer and a consultant
      radiologist. The sample was a consecutive sample of adult out-patients over a 3
      month period, with no exclusion. The length of time of the enema and the numbers
      and grades of staff involved in the procedure were recorded. This was translated
      into staffing costs using the appropriate pay scales. RESULTS: The barium enemas
      performed by the superintendent radiographer were more cost-effective than those
      performed by the consultant radiologist (pound 1406 for 100 radiographer
      performed barium enemas compared to pound 1787 for 100 carried out by the
      consultant radiologist). CONCLUSION: In terms of staffing costs, radiographers
      performing barium enemas not only liberates radiologist time, it is also a cost
      effective method of providing an out-patient barium enema service.

PMID- 11977947
TI  - Are referring clinicians aware of patients at risk from intravenous injection of
      iodinated contrast media?
AB  - AIM: The purpose of our study was to assess the level of awareness of referring
      clinicians to populations at risk for complications of intravascular
      administration of iodinated contrast media. SUBJECTS AND METHODS: Two hundred and
      three physicians from three university hospitals completed an anonymous
      questionnaire regarding risk factors and contraindications to the intravenous
      administration of iodinated contrast media. The questionnaire included medical
      conditions with increased risk for anaphylactoid reaction (asthma, hay fever and
      food allergy) as well as chemotoxic (ischaemic heart disease, phaeochromocytoma
      and myasthenia gravis) adverse reactions, some with dependence on renal function
      (metformin treatment, diabetes mellitus and multiple myeloma). Two additional
      multiple-choice questions addressed pre-medication protocols and risk of
      nephrotoxicity in diabetic patients. RESULTS: Asthma, food allergy and hay fever
      were recognized as risk factors by 81.3%, 77.8% and 61.6% of respondents
      respectively, while ischaemic heart disease, phaeochromocytoma and myasthenia
      gravis were defined as such only by 9.8%, 30.0% and 28.6% respectively. Metformin
      treatment, diabetes mellitus and multiple myeloma, in the presence of normal
      renal function, were considered as risk factors by 46.3%, 38.9% and 58.1% of
      respondents respectively. One of the generally accepted pre-medication protocols
      was selected by 89.8%. The risk of nephrotoxicity in a diabetic patient was
      correctly assessed by 63.5% of respondents. CONCLUSION: We found a relatively
      high awareness among referring clinicians of a potential anaphylactoid reaction
      and nephrotoxicity due to iodinated contrast media. However, additional
      chemotoxic adverse reactions are less well known. Future efforts to improve
      communication between clinicians and radiologists should be focused in this
      direction.

PMID- 11977948
TI  - Ultrasound diagnosis of infantile hypertrophic pyloric stenosis: determinants of
      pyloric length and the effect of prematurity.
AB  - AIM: To evaluate the determinants of sonographic measurements of pyloric length
      and muscle thickness in infants with hypertrophic pyloric stenosis (HPS) and to
      determine whether infants born prematurely have proportionately smaller
      measurements. MATERIALS AND METHODS: A retrospective review was carried out of
      190 infants operated on for HPS at Bristol Children's Hospital over a 5-year
      period. Sonographic measurements of pyloric length and muscle thickness were
      related to age, history of prematurity, weight, sex and family history of HPS.
      RESULTS: Pyloric length in infants with HPS was significantly greater in those
      born at term compared to those born prematurely (18.6 mm [SD 2.2] vs 17.3 mm [SD
      3.1], P = 0.043); this was explainable by body weight, with length increasing by
      1.13 mm (SE 0.35) per kilogram (P = 0.002). There was no significant relationship
      with measured muscle thickness. CONCLUSION: Sonographic measurement of pyloric
      length is strongly correlated with the weight of the infant, irrespective of
      other factors. The relationship of length and weight may be useful in confirming
      the presence of HPS in small and premature infants.

PMID- 11977949
TI  - 3D CT versus axial helical CT versus conventional tomography in the
      classification of acetabular fractures: a ROC analysis.
AB  - AIM: To assess the diagnostic power of three-dimensional computed tomography (3D
      CT), axial helical computed tomography (CT) and conventional tomography in the
      classification of acetabular fractures by interdisciplinary review. MATERIALS AND
      METHODS: Receiver operating characteristics (ROCs) were assessed for two
      radiologists and two surgeons blinded to the presence of acetabular fractures in
      an animal model (a total of 62 porcine hips, 40 of them with artificial
      acetabular fractures). Main target parameter was the diagnostic accuracy in the
      classification of the artificial fractures following Judet et al. RESULTS: ROC
      analysis for radiologists showed A(z) values of 0.83 for 3D CT, 0.81 for axial
      helical CT, and 0.78 for conventional tomography; differences between the three
      techniques were not significant (P = 0.46-0.73). A(z) values for the surgeons
      were 0.87 for 3D CT, 0.68 for axial helical CT, and 0.60 for conventional
      tomography; 3D CT was significantly better than axial helical CT (P = 0.01) and
      conventional tomography (P = 0.001). The differences between axial helical CT and
      conventional tomography were not significant (P = 0.37). CONCLUSION: Acetabular
      fractures are best classified by 3D CT, followed by axial helical CT and
      conventional tomography when assessed by surgeons. 3D CT did not provide any
      additional significant benefit in the classification performed by radiologists.

PMID- 11977950
TI  - Ultrasonography of acute and chronic tumoral calcinosis.

PMID- 11977951
TI  - Pelvic fibrosis.

PMID- 11977952
TI  - Plain radiograph and renal tract ultrasound in the management of children with
      renal tract calculi - a reply.

PMID- 11977953
TI  - The Canadian CT Head Rule for patients with minor head injury: consequences for
      radiology departments in the U.K.

PMID- 11977978
TI  - Egg activation at fertilization: where it all begins.
AB  - A centrally important factor in initiating egg activation at fertilization is a
      rise in free Ca(2+) in the egg cytosol. In echinoderm, ascidian, and vertebrate
      eggs, the Ca(2+) rise occurs as a result of inositol trisphosphate-mediated
      release of Ca(2+) from the endoplasmic reticulum. The release of Ca(2+) at
      fertilization in echinoderm and ascidian eggs requires SH2 domain-mediated
      activation of a Src family kinase (SFK) and phospholipase C (PLC)gamma. Though
      some evidence indicates that a SFK and PLC may also function at fertilization in
      vertebrate eggs, SH2 domain-mediated activation of PLC gamma appears not to be
      required. Much work has focused on identifying factors from sperm that initiate
      egg activation at fertilization, either as a result of sperm-egg contact or sperm
      egg fusion. Current evidence from studies of ascidian and mammalian fertilization
      favors a fusion-mediated mechanism; this is supported by experiments indicating
      that injection of sperm extracts into eggs causes Ca(2+) release by the same
      pathway as fertilization.

PMID- 11977979
TI  - Truncation of c-fes via gene targeting results in embryonic lethality and
      hyperproliferation of hematopoietic cells.
AB  - The c-fes protooncogene encodes a nonreceptor tyrosine kinase (Fes) implicated in
      cytokine receptor signal transduction, granulocyte survival, and myeloid
      differentiation. To study the role of c-fes during myelopoiesis, we generated
      embryonic stem (ES) cells with a targeted disruption of the c-fes locus. Targeted
      mutagenesis deletes the C-terminal SH2 and tyrosine kinase domains of c-fes
      (referred to as c-fes(Delta c/Delta c)). We demonstrate that the c-fes(Delta
      c/Delta c) allele results in a truncated Fes protein that retains the N-terminal
      oligomerization domain, but lacks both the SH2 and the tyrosine kinase domain. In
      vitro differentiation of c-fes(Delta c/Delta c) ES cells results in
      hyperproliferation of an early myeloid cell. Generation of c-fes(Delta c/Delta c)
      mutant chimeric mice causes lethality by E13.5 with embryos exhibiting
      pleiotropic defects, the most striking being cardiovascular abnormalities. These
      results establish that c-fes is an important regulator of myeloid cell
      proliferation and embryonic development.

PMID- 11977980
TI  - Integrin signaling regulates blastocyst adhesion to fibronectin at implantation:
      intracellular calcium transients and vesicle trafficking in primary trophoblast
      cells.
AB  - Accumulating evidence indicates that the endometrial extracellular matrix (ECM)
      modulates trophoblast adhesion during mouse blastocyst implantation. In previous
      studies of adhesion-competent mouse blastocysts, we have demonstrated that
      integrin-mediated fibronectin (FN)-binding activity on the apical surface of
      trophoblast cells is initially low, but becomes strengthened after embryos are
      exposed to FN. In the present study, we have examined whether the ligand-induced
      upregulation of trophoblast adhesion to FN is mediated by integrin signaling. The
      strengthening of adhesion to FN required integrin ligation, which rapidly
      elevated cytoplasmic-free Ca(2+). Chelation of intracellular Ca(2+) using BAPTA
      AM, or inhibition of the Ca(2+)-dependent proteins, protein kinase C or
      calmodulin, significantly attenuated the effect of FN on binding activity.
      Furthermore, direct elevation of cytoplasmic Ca(2+) levels with ionomycin
      upregulated FN-binding activity, demonstrating that Ca(2+) signaling is required
      and sufficient for strong adhesion to FN. Ca(2+) signaling may induce protein
      trafficking, a known requirement for ligand-induced upregulation of FN-binding
      activity. Indeed, intracellular vesicles accumulated in adhesion-competent
      blastocysts, but were absent after exposure to either FN or ionomycin. These
      findings suggest that, during implantation, contact between peri-implantation
      blastocysts and FN elevates intracellular Ca(2+), which strengthens trophoblast
      adhesion to ECM through protein redistribution.

PMID- 11977981
TI  - Indian hedgehog as a progesterone-responsive factor mediating epithelial
      mesenchymal interactions in the mouse uterus.
AB  - Genes encoding components of the hedgehog signaling pathway are dynamically
      expressed in the mouse uterus preparing for implantation. Indian hedgehog (Ihh),
      patched (Ptc), and Gli3 are expressed at low levels in the endometrial epithelium
      on day 1 of pregnancy. Transcription of Ihh increases dramatically in the luminal
      epithelium and glands from day 3, reaching very high levels on day 4. Over the
      same period, Ptc, Gli1, Gli2, and noggin are strongly upregulated in the
      underlying mesenchymal stroma. Transcription of Ihh in ovariectomized mice is
      induced by progesterone but not by estrogen. Lower induction of Ihh, Ptc, and
      Hoxa10 is seen in response to progesterone in the uteri of Pgr(-/-) mutant mice
      lacking progesterone nuclear steroid receptor. This finding suggests that the
      hormone may regulate Ihh through both nuclear receptor-dependent and -independent
      pathways. We describe a method for culturing uterine explants in the absence of
      epithelium. Under these conditions, recombinant N-SHH protein promotes the
      proliferation of mesenchyme cells and the expression of noggin. We propose that
      IHH made by the epithelium normally functions as a paracrine growth factor for
      stromal cells during the early stages of pregnancy.

PMID- 11977982
TI  - Significance of bone morphogenetic protein-4 function in the initial
      myofibrillogenesis of chick cardiogenesis.
AB  - The heart is the first organ to form and function during vertebrate
      embryogenesis. Using a secreted protein, noggin, which specifically antagonizes
      bone morphogenetic protein (BMP)-2 and -4, we examined the role played by BMP
      during the initial myofibrillogenesis in chick cultured precardiac mesoendoderm
      (mesoderm + endoderm; ME). Conditioned medium from COS7 cells transfected with
      Xenopus noggin cDNA inhibited the expression of sarcomeric proteins (such as
      sarcomeric alpha-actinin, Z-line titin, and sarcomeric myosin), and so
      myofibrillogenesis was perturbed in cultured stage 4 precardiac ME; however, it
      did not inhibit the expression of smooth muscle alpha-actin (the first isoform of
      alpha-actin expressed during cardiogenesis). In cultured stage 5 precardiac ME,
      noggin did not inhibit either the formation of I-Z-I components or the expression
      of sarcomeric myosin, but it did inhibit the formation of A-bands. Although BMP4
      was required to induce expressions of sarcomeric alpha-actinin, titin, and
      sarcomeric myosin in cultured stage 6 posterolateral mesoderm (noncardiogenic
      mesoderm), smooth muscle alpha-actin was expressed without the addition of BMP4.
      Interestingly, in cultured stage 6 posterolateral mesoderm, BMP2 induced the
      expressions of sarcomeric alpha-actinin and titin, but not of sarcomeric myosin.
      These results suggest that (1) BMP4 function lies upstream of the initial
      formation of I-Z-I components and A-bands separately in a stage-dependent manner,
      and (2) at least two signaling pathways are involved in the initial cardiac
      myofibrillogenesis: one is an unknown pathway responsible for the expression of
      smooth muscle alpha-actin; the other is BMP signaling, which is involved in the
      expression of sarcomeric alpha-actinin, titin, and sarcomeric myosin.

PMID- 11977983
TI  - Dynamics of Dnmt1 methyltransferase expression and intracellular localization
      during oogenesis and preimplantation development.
AB  - The imprinting of mammalian genes depends on the maintenance of DNA methylation
      patterns during pre- and postimplantation development. Dnmt1o is a variant form
      of the somatically expressed Dnmt1 cytosine methyltransferase that is synthesized
      and stored in the oocyte cytoplasm and trafficks to the eight-cell nucleus during
      preimplantation development, where it maintains DNA methylation patterns on
      alleles of imprinted genes. Transcripts encoding Dnmt1 are present in
      preimplantation embryos, suggesting that Dnmt1 protein is also expressed in the
      preimplantation embryo, and may account for maintenance methylation at
      preimplantation stages other than the eight-cell embryo. However, using an
      antibody that detects Dnmt1, but not Dnmt1o, no Dnmt1 protein was detected on
      immunoblots or by immunocytochemical staining in wildtype preimplantation
      embryos. Moreover, Dnmt1 protein produced in the oocyte from a modified Dnmt1
      allele, Dnmt1(1s/1o), trafficked to nuclei of eight-cell embryos, but not to
      nuclei of other stages. The highly restricted nuclear localization patterns of
      oocyte-derived Dnmt1o and Dnmt1 during preimplantation development add further
      support to the notion that DNA methyltransferases other than Dnmt1 are required
      for maintaining imprints during preimplantation development.

PMID- 11977984
TI  - DSF nuclear receptor acts as a repressor in culture and in vivo.
AB  - Loss-of-function mutations affecting the dissatisfaction (DSF) nuclear receptor
      alter both sexual behavior and the sex-specific nervous system in Drosophila. As
      a step toward understanding the way DSF controls development and function of the
      nervous system, we have analyzed the regulatory activities of the DSF protein.
      DSF prefers an atypical DNA half site, AAGTCA. Wild-type DSF, but not the point
      mutant DSF(7), monomerically binds and represses reporter constructs bearing this
      site. DSF also contains an atypically long, 356-amino-acid hinge separating its
      DNA-binding domain (DBD) and ligand-binding domain (LBD). The hinge contains at
      least two functions: a region that drastically lowers DNA-binding efficiency in
      vitro, and an amino-terminal repressive domain. The DBD and LBD of DSF, along
      with major portions of the hinge, are highly conserved in other insects. Ectopic
      expression of DSF in Drosophila imaginal discs results in developmental
      disruptions in disc-derived tissues, disruptions which are largely suppressed
      when DSF is fused to the VP16 activation domain, consistent with a repressive
      role for DSF. Finally, when tethered to DNA, DSF's hinge and LBD regions act as
      strong transcriptional repressors in multiple larval and pupal tissues, including
      many DSF-expressing tissues. These results suggest DSF can repress transcription
      in vivo, that repression is largely responsible for its ectopic expression
      phenotypes, and that repression may be a key component of normal DSF function.

PMID- 11977985
TI  - 3D-DIASemb: a computer-assisted system for reconstructing and motion analyzing in
      4D every cell and nucleus in a developing embryo.
AB  - A computer-assisted three-dimensional (3D) system, 3D-DIASemb, has been developed
      that allows reconstruction and motion analysis of cells and nuclei in a
      developing embryo. In the system, 75 optical sections through a live embryo are
      collected in the z axis by using differential interference contrast microscopy.
      Optical sections for one reconstruction are collected in a 2.5-s period, and this
      process is repeated every 5 s. The outer perimeter and nuclear perimeter of each
      cell in the embryo are outlined in each optical section, converted into beta
      spline models, and then used to construct 3D faceted images of the surface and
      nucleus of every cell in the developing embryo. Because all individual components
      of the embryo (i.e., each cell surface and each nuclear surface) are individually
      reconstructed, 3D-DIASemb allows isolation and analysis of (1) all or select
      nuclei in the absence of cell surfaces, (2) any single cell lineage, and (3) any
      single nuclear lineage through embryogenesis. Because all reconstructions
      represent mathematical models, 3D-DIASemb computes over 100 motility and dynamic
      morphology parameters for every cell, nucleus, or group of cells in the
      developing embryo at time intervals as short as 5 s. Finally, 3D-DIASemb
      reconstructs and motion analyzes cytoplasmic flow through the generation and
      analysis of "vector flow plots." To demonstrate the unique capabilities of this
      new technology, a Caenorhabditis elegans embryo is reconstructed and motion
      analyzed through the 28-cell stage. Although 3D-DIASemb was developed by using
      the C. elegans embryo as the experimental model, it can be applied to other
      embryonic systems. 3D-DIASemb therefore provides a new method for reconstructing
      and motion analyzing in 4D every cell and nucleus in a live, developing embryo,
      and should provide a powerful tool for assessing the effects of drugs,
      environmental perturbations, and mutations on the cellular and nuclear dynamics
      accompanying embryogenesis.

PMID- 11977986
TI  - Characterization of MPF and MAPK activities during meiotic maturation of Xenopus
      tropicalis oocytes.
AB  - Resumption of meiosis in oocytes of Xenopus tropicalis required translation but
      not transcription, and was marked by the appearance of a white spot and a dark
      ring, coincident with entry into metaphase I and the onset of anaphase I,
      respectively. Cyclin B(2)/p34(cdc2) activity increased prior to the first meiotic
      division, declined at the onset of anaphase I, and subsequently increased again.
      The capacity of egg cytoplasm to induce germinal vesicle breakdown (GVBD) was
      inhibited by cycloheximide, despite the fact that these oocytes contained cyclin
      B(2)/p34(cdc2) complexes. However, cycloheximide-treated oocytes underwent GVBD
      following injection of constitutively active mitogen-activated protein kinase
      (MAPK) kinase 2 (MEK2), p33(Ringo), or Delta 90 cyclin B. MAPK activity increased
      just prior to the first meiotic division and remained stable thereafter. Although
      injection of constitutively active MEK2 induced GVBD, treatment with the MEK
      inhibitors U0126 or anthrax lethal factor delayed GVBD and prevented spindle
      formation. Interestingly, the ability of egg cytoplasm to induce GVBD was
      unaffected by the inhibition of MEK activity. Our results indicate that the
      synthesis of a novel or short-lived protein(s) which acts in a MEK-independent
      fashion is required in order for egg cytoplasm to induce GVBD in X. tropicalis
      oocytes.

PMID- 11977987
TI  - Oligodendrocyte precursor cells from different brain regions express divergent
      properties consistent with the differing time courses of myelination in these
      regions.
AB  - Different CNS regions exhibit different temporal patterns of oligodendrocyte
      generation and myelinogenesis. Characterization of oligodendrocyte-type-2
      astrocyte progenitor cells (here abbreviated as O-2A/OPCs) isolated from
      different regions indicates these developmental patterns are consistent with
      properties of the specific O-2A/OPCs resident in each region. Marked differences
      were seen in self-renewal and differentiation characteristics of O-2A/OPCs
      isolated from cortex, optic nerve and optic chiasm. In conditions where optic
      nerve-derived O-2A/OPCs generated oligodendrocytes within 2 days,
      oligodendrocytes arose from chiasm-derived cells after 5 days and from cortical O
      2A/OPCs only after 7-10 days. These differences, which appear to be cell
      intrinsic (and may be related to intracellular redox state), were manifested both
      in reduced percentages of clones producing oligodendrocytes and in a lesser
      representation of oligodendrocytes in individual clones. In addition,
      responsiveness of optic nerve-, chiasm- and cortex-derived O-2A/OPCs to thyroid
      hormone (TH) and ciliary neurotrophic factor (CNTF), well-characterized inducers
      of oligodendrocyte generation, was inversely related to the extent of self
      renewal observed in basal division conditions. Our results demonstrate hitherto
      unrecognized complexities among the precursor cells thought to be the immediate
      ancestors of oligodendrocytes, and suggest that the properties of these different
      populations may contribute to the diverse time courses of myelination in
      different CNS regions.

PMID- 11977988
TI  - AMP-activated protein kinase and familial Wolff-Parkinson-White syndrome: new
      perspectives on heart development and arrhythmogenesis.

PMID- 11977989
TI  - Biventricular pacing in patients with heart failure and intraventricular
      conduction delay: state of the art and perspectives. The European view.

PMID- 11977990
TI  - Watch the belly to protect the heart.

PMID- 11977991
TI  - Has the mortality rate from acute myocardial infarction fallen substantially in
      recent years?

PMID- 11977992
TI  - SNP at your own risk.

PMID- 11977993
TI  - The deleterious effects of an irregular RR interval.

PMID- 11977994
TI  - Catheter ablation of untolerated ventricular tachycardia--a new front line.

PMID- 11977995
TI  - Is prophylaxis the best use of the ICD?

PMID- 11977996
TI  - Abdominal obesity is associated with increased risk of acute coronary events in
      men.
AB  - AIMS: The purpose of the study was to investigate the associations of abdominal
      obesity and overall obesity with the risk of acute coronary events. METHODS AND
      RESULTS: Body mass index indicating overall obesity and waist-to-hip ratio and
      waist circumference indicating abdominal obesity were measured for 1346 Finnish
      men aged 42-60 years who had neither cardiovascular disease nor cancer at
      baseline. There were 123 acute coronary events during an average follow-up of
      10.6 years. In Cox regression analyses adjusted for confounding factors, waist-to
      hip ratio (P=0.009), waist circumference (P=0.010) and body mass index (P=0.013)
      as continuous variables were associated directly with the risk of coronary
      events. These associations were in part explained by blood pressure, diabetes,
      fasting serum insulin, serum lipids, plasma fibrinogen, and serum uric acid.
      Waist-to-hip ratio of > or =0.91 was associated with a nearly threefold risk of
      coronary events. Waist-to-hip ratio provided additional information beyond body
      mass index in predicting coronary heart disease, whereas body mass index did not
      add to the predictive value of waist-to-hip ratio. Abdominal obesity combined
      with smoking and poor cardiorespiratory fitness increased the risk of coronary
      events 5.5 and 5.1 times, respectively. CONCLUSIONS: Abdominal obesity is an
      independent risk factor for coronary heart disease in middle-aged men and even
      more important than overall obesity. Since the effect of abdominal obesity was
      strongest in smoking and unfit men, the strategy for lifestyle modification to
      prevent coronary heart disease should address these issues jointly.

PMID- 11977997
TI  - What is the real hospital mortality from acute myocardial infarction?
      Epidemiological vs clinical view.
AB  - AIMS: To examine the general influence of the definition of fatal and non-fatal
      acute myocardial infarction and coronary deaths on the estimation of in-hospital
      case-fatality, and to show how the definition of acute myocardial infarction
      influences time-trends of hospital mortality over 11 years. METHODS AND RESULTS:
      As part of the World Health Organization's MONICA (multinational Monitoring of
      Trends and Determinants in Cardiovascular Disease) Project in Augsburg all
      patients aged 25-74 years with a suspected diagnosis of acute myocardial
      infarction who were hospitalized in the study region's major clinic were
      registered prospectively between 1985 to 1995 (n=4889). Patient information,
      including short-term survival status, was obtained from medical records, by
      interview of surviving patients, and municipal death certificate files which were
      validated by an extended identification and validation process. In-hospital case
      fatality was estimated according to different definitions which closely followed
      the international MONICA criteria. Epidemiological definitions comprised definite
      and possible acute myocardial infarction, and events with unclassifiable deaths,
      while the clinical definition was restricted to definite infarction. Overall,
      case fatality by the epidemiological definitions was 28 to 29.8% (23.5% of those
      treated in a coronary care unit) compared to 13.5% using the clinical definition.
      While over the 11 years, the reduction in case fatality according to the
      epidemiological definitions was modest, highly significant decreases were
      observed by applying the clinical definition (from 15.8% in 1985-1988 to 10.8% in
      1993-1995, P<0.001 adjusted for age and sex). The discrepancy in case fatality
      between the definitions is explained by the high proportion of patients who die
      very early (about 70% of all fatal events during the first 24 h) with the
      consequence of missing data which may preclude a definite diagnosis of acute
      myocardial infarction. CONCLUSIONS: Applying a broader definition of acute
      myocardial infarction reveals that in-hospital mortality is higher than believed
      until now, and it implies that our efforts must be intensified to reduce overall
      in-hospital coronary heart disease mortality.

PMID- 11977998
TI  - The 5A6A polymorphism in the promoter of the stromelysin-1 (MMP3) gene as a risk
      factor for restenosis.
AB  - AIMS: Intracoronary ultrasound studies in humans show that chronic remodelling
      rather than neointimal hyperplasia is the mechanism of restenosis. Stent
      implantation limits this remodelling process and significantly reduces
      restenosis. MMP3 (Stromelysin-1), a member of the matrix metalloproteinase family
      may play a role in this remodelling. We used a functional polymorphism (with
      alleles designated 5A or 6A) in the promoter of the MMP3 gene to examine the
      possible role of MMP3 in restenosis. METHODS AND RESULTS: Genotypes were
      determined in a series of consecutive patients who underwent conventional balloon
      coronary angioplasty without stenting (n=287) or who also had successful
      implantation of a Palmaz-Schatz stent (stent) (n=198). For all patients
      restenosis was estimated at 6 months using quantitative computer-assisted
      angiography. The minimal luminal diameters before and after the procedures did
      not differ significantly between genotypes. At follow-up in the patients without
      stent, those with the 6A6A genotype had an increased degree of restenosis after
      coronary angioplasty compared to those with one or more 5A alleles, with a
      greater diameter stenosis (52+/-21% vs 45+/-19%, P=0.012), and a greater late
      loss (0.58+/-0.59 mm vs 0.38+/-0.59 mm, P=0.038). By contrast, in the stented
      patients MMP3 genotype was not associated with any angiographically determined
      measure of vessel dimensions. CONCLUSIONS: These data imply the involvement of
      MMP3 in chronic remodelling after conventional balloon angioplasty, and suggest
      that the 6A6A MMP3 genotype is a genetic susceptibility factor for restenosis
      after angioplasty without stenting.

PMID- 11977999
TI  - Association of plasma homocysteine with restenosis after percutaneous coronary
      angioplasty.
AB  - AIMS: Restenosis after percutaneous coronary angioplasty remains an important
      limitation of this procedure. This study evaluates whether elevated total plasma
      homocysteine levels contribute to the development of restenosis after coronary
      angioplasty. METHODS AND RESULTS: Two hundred and five patients were recruited
      after successful angioplasty of at least one coronary stenosis (> or =50%). End
      points were restenosis (> or =50%) and a composite of major adverse cardiac
      events. Of the 205 patients, 183 (89.3%) underwent 6 months angiographic follow
      up. Patients with restenosis had significantly higher homocysteine levels than
      those without (10.9+/- 3.9 micromol x l(-1) vs 9.3+/-3.8 micromol x l(-1),
      P<0.01). Homocysteine levels were significantly correlated to follow-up diameter
      stenosis (r=0.24, P=0.0001), especially in small vessels (<3 mm) treated with
      balloon angioplasty only (r=0.40, P<0.0005). Late lumen loss at follow-up was
      significantly smaller with homocysteine levels below 9 micromol x l(-1) (0.62+/
      0.82 mm vs 0.90+/-0.77 mm, P<0.01). Restenosis rate (25.3% vs 50.0%, P<0.001) and
      major adverse cardiac events (15.7% vs 28.4%, P<0.05) were also significantly
      lower in patients with homocysteine levels below 9 micromol x l(-1). Multivariate
      analysis did not weaken these findings. CONCLUSION: Total plasma homocysteine is
      a strong predictor of restenosis and major adverse cardiac events after coronary
      angioplasty. Thus, plasma homocysteine appears to be an important cardiovascular
      risk factor influencing outcome after successful coronary angioplasty.

PMID- 11978000
TI  - Effect of acute atrial fibrillation on phasic coronary blood flow pattern and
      flow reserve in humans.
AB  - AIMS: To assess the effect of experimentally induced atrial fibrillation on
      coronary flow in humans. METHODS AND RESULTS: In 16 patients (10 men, mean age
      43+/-13 years) with normal coronary vessels, baseline and hyperaemic blood
      pressure and Doppler phasic coronary flow velocity were measured, using a 0.014
      inch intracoronary Doppler flow wire, during sinus rhythm, experimentally induced
      atrial fibrillation, and right atrial pacing at a similar heart rate to that
      during atrial fibrillation. Coronary flow velocity integral per minute increased
      significantly during both right atrial pacing and atrial fibrillation compared to
      sinus rhythm, but during right atrial pacing the increase was greater (85+/-43%
      vs 52+/-25%, P<0.001). This difference persisted even after correction for the
      product of heart rate and blood pressure (1.15+/-0.51 vs 0.97+/-0.46,
      respectively, P<0.02). In a further 12 paced patients (seven men, mean age 54+/
      10 years) with complete atrioventricular block the induction of atrial
      fibrillation (atrial fibrillation with regular RR interval) caused no significant
      changes in coronary flow velocity variables. CONCLUSIONS: Acute atrial
      fibrillation in humans causes an increase in coronary flow that is, however,
      insufficient to compensate for the augmented myocardial oxygen demand, mainly
      because of the irregularity in the ventricular rhythm that exists during atrial
      fibrillation.

PMID- 11978001
TI  - Non-contact mapping to guide catheter ablation of untolerated ventricular
      tachycardia.
AB  - AIMS: The role of a novel non-contact mapping system (ESI 3000, Endocardial
      Solutions) to guide radiofrequency catheter ablation of untolerated ventricular
      tachycardia was investigated in 17 patients; 11 with prior myocardial infarction,
      three with arrhythmogenic right ventricular dysplasia, and three with idiopathic
      dilated cardiomyopathy. METHODS: Twenty-seven monomorphic ventricular
      tachycardias were induced (mean cycle 320+/-60 ms, range 230-450 ms), mapped for
      15-20 s, and terminated by overdrive pacing or DC shock. Off-line analysis of
      isopotential activation mapping was performed to identify the diastolic pathway
      and/or the exit point of the ventricular tachycardia reentry circuit.
      Radiofrequency current was applied to create a line of block across the diastolic
      pathway or around the exit point. RESULTS: All 27 ventricular tachycardias were
      mapped with the non-contact system. The endocardial exit point (-7+/-15 ms before
      QRS onset) was defined in 21/21 postinfarction ventricular tachycardias, in 3/3
      arrhythmogenic right ventricular dysplasia and in 1/3 idiopathic dilated
      cardiomyopathy ventricular tachycardias, respectively. The diastolic pathway
      (earliest endocardial diastolic activity: -65+/-49 ms before QRS onset) was
      identified in 17/21 postinfarction ventricular tachycardias, in 1/3
      arrhythmogenic right ventricular dysplasia and in 1/3 idiopathic dilated
      cardiomyopathy ventricular tachycardias, respectively. Catheter ablation was
      performed in 25/27 ventricular tachycardias (93%) in 15/17 patients (88%): 16/25
      ventricular tachycardias (64%) were successfully ablated in 10/17 patients (59%).
      Catheter ablation was not performed in two patients or proved unsuccessful in
      five patients. At a follow-up of 15+/-5 months, there was no recurrence of
      documented ventricular tachycardia in all 10 patients with successful catheter
      ablation; in two of them a previously non-documented ventricular tachycardia
      occurred. A high recurrence of ventricular tachycardia was observed in patients
      with a failed procedure (5/7: 71%). No major complication or death occurred.
      CONCLUSIONS: Non-contact mapping can be effectively used to map and guide
      radiofrequency catheter ablation of untolerated ventricular tachycardias. Given
      the favourable acute and clinical long-term results, this approach proves to be
      more effective in patients with postinfarction ventricular tachycardias, in
      comparison to patients with arrhythmogenic right ventricular dysplasia and
      idiopathic dilated cardiomyopathy.

PMID- 11978003
TI  - Increasing fibroblast response to materials using nanotopography: morphological
      and genetic measurements of cell response to 13-nm-high polymer demixed islands.
AB  - It is becoming clear that cells can respond not only to micometric scale
      topography, but may also to nanometric scale topography. The production of
      reproducibly sized nanometric features has relied heavily on expensive and time
      consuming methods of manufacture, such as electron beam lithography. Polymer
      demixing of polystyrene and polybromostyrene has been found to produce nanoscale
      islands of reproducible height, and the islands have been previously shown to
      effect cell spreading compared to planar surfaces. This study observes
      morphological, cytoskeletal, and molecular changes in fibroblast reaction to 13
      nm-high islands. The methods employed include scanning electron microscopy,
      fluorescent microscopy, and 1718 gene microarray. The results show that the cells
      respond to the islands by broad gene up-regulation, notably in the areas of cell
      signaling, proliferation, cytoskeleton, and production of extracellular matrix
      proteins. Microscopical results provide confirmation of the microarray findings.

PMID- 11978004
TI  - Spatial preservation of nuclear chromatin architecture during three-dimensional
      fluorescence in situ hybridization (3D-FISH).
AB  - 3D-FISH has become a major tool for studying the higher order chromatin
      organization in the cell nucleus. It is not clear, however, to what extent
      chromatin arrangement in the nucleus after fixation and 3D-FISH still reflects
      the order in living cells. To study this question, we compared higher order
      chromatin arrangements in living cells with those found after the 3D-FISH
      procedure. For in vivo studies we employed replication labeling of DNA with Cy3
      conjugated nucleotides and/or chromatin labeling by GFP-tagged histone 2B. At the
      light microscope level, we compared the intranuclear distribution of H2B-GFP
      tagged chromatin and the positions of replication-labeled chromatin domains in
      the same individual cells in vivo, after fixation with 4% paraformaldehyde, and
      after 3D-FISH. Light microscope data demonstrate a high degree of preservation of
      the spatial arrangement of approximately 1-Mb chromatin domains. Subsequent
      electron microscope investigations of chromatin structure showed strong
      alterations in the ultrastructure of the nucleus caused mainly by the heat
      denaturation step. Through this step chromatin acquires the appearance of a net
      with mesh size of 50-200 nm roughly corresponding to the average displacement of
      the chromatin domains observed at light microscope level. We conclude that 3D
      FISH is a useful tool to study chromosome territory structure and arrangements
      down to the level of approximately 1-Mb chromatin domain positions. However,
      important ultrastructural details of the chromatin architecture are destroyed by
      the heat denaturation step, thus putting a limit to the usefulness of 3D-FISH
      analyses at nanometer scales.

PMID- 11978005
TI  - Lactate stimulates fibroblast expression of hyaluronan and CD44: the Warburg
      effect revisited.
AB  - Hyaluronan, a high-molecular-weight glycosaminoglycan of the extracellular
      matrix, is prominent during rapid tissue growth and repair. It stimulates cell
      motility and hydrates tissue, providing an environment that facilitates cell
      movement. Markedly enhanced levels of hyaluronan also occur in the stroma
      surrounding human cancers, thus providing an environment that promotes spread of
      cancer cells. The ability of malignant tumors to generate lactate, even in the
      presence of adequate oxygen, is known as the Warburg effect. Early in wound
      healing as blood and oxygen supply decrease, lactate levels increase, as does
      stromal hyaluronan, suggesting a cause-and-effect relationship. Similarly,
      peritumor stromal fibroblast hyaluronan may be a response to cancer cell lactate.
      To test this, fibroblasts were cultured in the presence of lactate. With
      increasing lactate, higher levels of hyaluronan were observed, as were levels of
      CD44 expression, the predominant receptor for hyaluronan. The ability of tumor
      cells to utilize anaerobic metabolism and to generate lactate, even in the
      presence of adequate supplies of oxygen, may be one of the mechanisms used to
      recruit host fibroblasts to deposit hyaluronan and to express CD44, thereby
      participating in the process of cancer invasion and metastasis.

PMID- 11978006
TI  - A form of cell death with some features resembling apoptosis in the
      amitochondrial unicellular organism Trichomonas vaginalis.
AB  - One of hallmarks of apoptosis is the degradation and concomitant compaction of
      chromatin. It is assumed that caspases and caspase-independent pathways are rate
      limiting for the development of nuclear apoptosis. The caspase-independent
      pathway involves apoptosis-inducing factor (AIF) and leads to DNA fragmentation
      and peripheral chromatin condensation. Both pathways are the result of activation
      of death signals that the mitochondrion receives, integrates, and responds to
      with the release of various molecules (e.g., cytochrome c and AIF). In fact, both
      pathways have in common the final point of the DNA fragmentation and the
      mitochondrial origin of molecules that initiate the apoptotic events. Here, we
      examine the question of whether apoptosis or apoptotic-like processes exist in a
      unicellular organism that lacks mitochondria. We herein show that a form of cell
      death with some features resembling apoptosis is indeed present in Trichomonas
      vaginalis. Characterization of morphological aspects implicated in this event
      together with the preliminary biochemical data provided may lead to new insight
      about the evolutionary relationships between the different forms of programmed
      cell death identified so far.

PMID- 11978007
TI  - Cx32 formation and/or Cx32-mediated intercellular communication induces
      expression and function of tight junctions in hepatocytic cell line.
AB  - Gap junctional intercellular communication (GJIC) is thought to play a crucial
      role in cell differentiation. Small gap junction plaques are frequently
      associated with tight junction strands in hepatocytes, suggesting that gap
      junctions may be closely related to the role of tight junctions in the
      establishment of cell polarity. To examine the exact role of gap junctions in
      regulating tight junctions, we transfected connexin 32 (Cx32), Cx26, or Cx43
      cDNAs into immortalized mouse hepatocytes derived from Cx32-deficient mice and
      examined the expression and function of the endogenous tight junction molecules.
      In transient wild-type Cx32 transfectants, immunocytochemistry revealed that
      endogenous occludin was in part localized at cell borders, where it was
      colocalized with Cx32, whereas neither was detected in parental cells. In Cx32
      null hepatocytes transfected with Cx32 truncated at position 220 (R220stop), wild
      type Cx26, or wild-type Cx43 cDNAs, occludin was not detected at cell borders. In
      stable wild-type Cx32 transfectants, occludin, claudin-1, and ZO-1 mRNAs and
      proteins were significantly increased compared to parental cells and all of the
      proteins were colocalized with Cx32 at cell borders. Treatment with a GJIC
      blocker, 18 beta-glycyrrhetinic acid, resulted in decreases of occludin and
      claudin-1 at cell borders in the stable transfectants. The induction of tight
      junction proteins in the stable transfectants was accompanied by an increase in
      both fence and barrier functions of tight junctions. Furthermore, in the stable
      transfectants, circumferencial actin filaments were also increased without a
      change of actin protein. These results indicate that Cx32 formation and/or Cx32
      mediated intercellular communication may participate in the formation of
      functional tight junctions and actin organization.

PMID- 11978009
TI  - Cell adhesion-mediated transformation of a human SCLC cell line is associated
      with the development of a normal phenotype.
AB  - Small cell lung carcinoma (SCLC) is a highly metastatic disease with a poor
      prognosis due to its resistance to current modes of therapy. SCLC cells appear to
      arise by oncogenic transformation of self-renewing pulmonary neuroendocrine
      cells, which have the potential to differentiate into a variety of lung
      epithelial cell lineages. Epithelial-mesenchymal conversion involved in such cell
      type transitions leads to the acquisition of an invasive and metastatic phenotype
      and may be critical for neoplastic progression and its eventual resistance to
      therapy. In order to investigate mechanisms involved in such transitions, a SCLC
      cell line was exposed to 5-bromodeoxyuridine. This treatment induced a dramatic
      conversion from non-substrate-adherent aggregates to monolayers of cells
      exhibiting an epithelioid phenotype. The phenotypic transition was concomitant
      with downregulation of vimentin, upregulation of cytokeratins, and cell-cell and
      cell-matrix adhesion molecules as well as redistribution of the actin
      cytoskeleton. The changes in the levels and organization of cell-cell and cell
      matrix adhesion molecules were correlated with an in vivo loss of tumorigenicity.

PMID- 11978008
TI  - Specific lectins map the distribution of fibronectin and beta 1-integrin on
      living MDCK cells.
AB  - The expression and dynamics of bound fibronectin and the sialylated integral
      membrane protein, beta 1-integrin, were analyzed on the apical membrane of living
      MDCK cells. Fibronectin was identified by its specific binding of fluorescent
      peanut agglutinin and sialylated beta 1-integrin by its binding of Sambucus nigra
      agglutinin. Confocal epifluorescence microscopy and laser scanning cytometry
      determined the distribution and abundance of binding sites of the two
      fluorescently labeled lectins. Both fibronectin and beta 1-integrin were
      restricted to specific regions uniformly distributed over the entire apical
      surface. Apical-surface fibronectin binding varied much more between cells than
      did the expression of beta 1-integrin. Sialylated beta 1-integrin colocalized
      >92% with membrane microplicae while fibronectin was unrelated to these surface
      structures. This lack of colocalization of the proteins was confirmed by double
      labeling experiments. From the maturation dependence of the fibronectin-binding
      capacity and the differences in protein turnover times, it was evident that
      fibronectin did not bind to sialylated beta 1-integrin. Furthermore,
      desialylation of beta 1-integrin uncovered additional fibronectin receptors on
      the apical membrane. We conclude that these lectins permit tracking of two
      membrane-associated glycoproteins in living cells and that fibronectin binds only
      to desialylated beta 1-integrin on MDCK cells.

PMID- 11978010
TI  - Annexin 2 "secretion" accompanying exocytosis of chromaffin cells: possible
      mechanisms of annexin release.
AB  - Annexin 2 is a Ca(2+)-dependent phospholipid-binding protein that is involved in
      secretion. Despite the fact that this protein does not have signals for its
      secretion, many reports have shown its presence in the extracellular milieu. Here
      we demonstrate that, upon stimulation of exocytosis in chromaffin cells, a
      fraction of annexin 2 is secreted into the culture medium. This release of
      annexin 2 is specific, correlated with catecholamine secretion, and independent
      of cell death. To explain the liberation of cytosolic annexin 2 into the medium,
      we propose and bring evidence for a mechanism of multiporic membrane disruption
      during membrane fusion. Prior, in cross-linking experiments, annexin 2 forms
      aggregates of high molecular weight, revealing its capacity to form networks.
      Second, immunoelectron microscopy studies of fused chromaffin granules revealed
      the presence of annexin 2 and membrane proteins inside the fused vesicles, as
      would be predicted by the multiporic hypotheses. These data suggest that annexin
      2 "secretion" in chromaffin cells is the consequence of membrane disruption
      during exocytosis. The role of annexin 2 in exocytosis is also discussed.

PMID- 11978011
TI  - Adenosine suppresses alpha(4)beta(7) integrin-mediated adhesion of T lymphocytes
      to colon adenocarcinoma cells.
AB  - The interaction of T lymphocytes with tumor cells, a key step in the antitumor
      immune response, is suppressed by adenosine, a nucleoside produced at increased
      levels within the hypoxic tumor environment. We have explored the mechanism by
      which adenosine interferes with the lymphocyte:tumor cell interaction. The
      adhesion of anti-CD3-stimulated T cells to syngeneic MCA-38 mouse colon
      adenocarcinoma cells did not involve LFA-1 (alpha(L)beta(2)) or VLA-5
      (alpha(5)beta(1)). However, antibodies against either lymphocyte alpha(4) or
      beta(7) (but not beta(1)) integrin subunits, or against VCAM-1 on the tumor
      cells, significantly suppressed adhesion, showing that the recognition of MCA-38
      cells by T cells is strongly dependent upon the association of alpha(4)beta(7) on
      the effector cells with VCAM-1 on the tumor targets. This association is
      modulated by adenosine: The ability of adenosine to suppress T cell adhesion to
      MCA-38 cells was lost if alpha(4)beta(7) was functionally blocked with anti
      alpha(4) antibodies (i) prior to or (ii) during the adhesion assay or if (iii)
      alpha(+)(4) cells were depleted from the T lymphocyte population. The binding of
      T cells to fibronectin through alpha(4)beta(1) was not suppressed by adenosine.
      We conclude that adenosine partially inhibits the interaction of T lymphocytes
      with tumor cells by blocking the function of integrin alpha(4)beta(7).

PMID- 11978012
TI  - Cell surface alpha 2,6 sialylation affects adhesion of breast carcinoma cells.
AB  - Tumor-associated alterations of cell surface glycosylation play a crucial role in
      the adhesion and metastasis of carcinoma cells. The aim of this study was to
      examine the effect of alpha 2,6-sialylation on the adhesion properties of breast
      carcinoma cells. To this end mammary carcinoma cells, MDA-MB-435, were sense
      transfected with sialyltransferase ST6Gal-I cDNA or antisense-transfected with a
      part of the ST6Gal-I sequence. Sense transfectants showed an enhanced ST6Gal-I
      mRNA expression and enzyme activity and an increased binding of the lectin
      Sambucus nigra agglutinin (SNA), specific for alpha 2,6-linked sialic acid.
      Transfection with ST6Gal-I in the antisense direction resulted in less enzyme
      activity and SNA reactivity. A sense-transfected clone carrying increased amounts
      of alpha 2,6-linked sialic acid adhered preferentially to collagen IV and showed
      reduced cell-cell adhesion and enhanced invasion capacity. In contrast, antisense
      transfection led to less collagen IV adhesion but enhanced homotypic cell-cell
      adhesion. In another approach, inhibition of ST6Gal-I enzyme activity by
      application of soluble antisense-oligodeoxynucleotides was studied. Antisense
      treatment resulted in reduced ST6 mRNA expression and cell surface 2,6
      sialylation and significantly decreased collagen IV adhesion. Our results suggest
      that cell surface alpha 2,6-sialylation contributes to cell-cell and cell
      extracellular matrix adhesion of tumor cells. Inhibition of sialytransferase
      ST6Gal-I by antisense-oligodeoxynucleotides might be a way to reduce the
      metastatic capacity of carcinoma cells.

PMID- 11978013
TI  - Stable inhibition of NF-kappa B in salivary gland cells does not enhance
      sensitivity to TNF-alpha-induced apoptosis due to upregulation of TRAF-1
      expression.
AB  - The transcription factor NF-kappa B inhibits the apoptotic response induced by
      TNF-alpha. However, in salivary gland cell clones (ACMT-6 and ACMT-7) in which NF
      kappa B activation was suppressed by introduction of a super-repressor form of I
      kappa B-alpha cDNA, TNF-alpha did not cause apoptosis. Thus, to investigate the
      molecular mechanism involved in the unresponsiveness of these cell clones to TNF
      alpha-induced apoptosis, we examined the effect of TNF-alpha on the expression of
      antiapoptotic proteins, including TNF receptor-associated factor (TRAF)-1, TRAF
      2, cellular inhibitor of apoptosis protein (cIAP)-1, and cIAP-2. Here we show
      that expression of TRAF-1 was commonly detected by treatment with TNF-alpha in
      ACMT-6, ACMT-7, and an empty vector-transfected cell clone (ACpRc-1) and that
      downregulation of TRAF-1 protein by either treatment with an antisense
      oligonucleotide or introduction of an antisense plasmid resulted in the induction
      of apoptosis in these cell clones. Our results, therefore, suggest that one of
      the mechanisms by which cells acquire resistance to TNF-alpha-induced apoptosis
      is a TNF-alpha induction of TRAF-1.

PMID- 11978014
TI  - Polyamine depletion induces apoptosis through mitochondria-mediated pathway.
AB  - Polyamines, namely putrescine, spermidine, and spermine, are essential for cell
      survival and proliferation. A decrease in intracellular polyamine levels is
      associated with apoptosis. In this study, we used inhibitors of polyamine
      biosynthesis to examine the effect of polyamine depletion. A combination of
      inhibitors of ornithine decarboxylase, S-adenosylmethionine decarboxylase, or
      spermidine synthase decreased intracellular polyamine levels and induced cell
      death in a WEHI231 murine B cell line. These cells exhibited apoptotic features
      including chromatin condensation and oligonucleosomal DNA fragmentation. Addition
      of exogenous polyamines reversed the observed features of apoptotic cell death.
      Similar effects were also observed in other cell lines: a human B cell line Ramos
      and a human T cell line Jurkat. Depletion of polyamines induced activation of
      caspase-3 and disruption of the mitochondrial membrane potential (Delta psi m).
      Inhibition of caspase activities by an inhibitor prevented the apoptotic nuclear
      changes but not Delta psi m disruption induced by polyamine depletion.
      Overexpression of Bcl-xl, an anti-apoptotic Bcl-2 family protein, completely
      inhibited Delta psi m disruption, caspase activation, and cell death. These
      results indicate that the depletion of intracellular polyamines triggers the
      mitochondria-mediated pathway for apoptosis, resulting in caspase activation and
      apoptotic cell death.

PMID- 11978054
TI  - In vivo characteristics of placental amino acid transport and metabolism in ovine
      pregnancy--a review.
AB  - The placental transport of amino acids which is nutritionally important is the
      net entry rate into the fetal circulation (the umbilical uptake). This entry rate
      is a function of transport across cell membranes, the effect of competition among
      amino acids for transport, particularly across the fetal surface of the
      trophoblast, and their metabolism and interconversion within the placenta. The
      result of these different interactive fluxes is that the relationship between
      maternal concentration and fetal supply of an amino acid differs for each amino
      acid. For some amino acids there are relatively large bidirectional fluxes at
      both the fetal and maternal surfaces of the placenta. These fluxes can be
      measured in vivo utilizing stable isotope methodology. There is an important
      interorgan exchange of amino acids between the placenta and fetal liver. This
      exchange is, at least in part, a function of the absence of gluconeogenesis in
      the fetal liver. Both glutamate and serine, which are released from the fetal
      liver, are taken up by the placenta from the fetal circulation and metabolized
      within the placenta.

PMID- 11978055
TI  - Implications of dietary fatty acids during pregnancy on placental, fetal and
      postnatal development--a review.
AB  - During pregnancy, the mother adapts her metabolism to support the continuous
      draining of substrates by the fetus. Her increase in net body weight (free of the
      conceptus) corresponds to the accumulation of fat depots during the first two
      thirds of gestation, switching to an accelerated breakdown of these during the
      last trimester. Under fasting conditions, adipose tissue lipolytic activity is
      highly enhanced, and its products, free fatty acids (FFA) and glycerol, are
      mainly driven to maternal liver, where FFA are converted to ketone bodies and
      glycerol to glucose, which easily cross the placenta and sustain fetal
      metabolism. Lipolytic products reaching maternal liver are also used for
      triglyceride synthesis that are released in turn to the circulation, where
      together with an enhanced transfer of triglycerides among the different
      lipoprotein fractions, and a decrease in extrahepatic lipoprotein lipase
      activity, increase the content of triglycerides in all the lipoprotein fractions.
      Long chain polyunsaturated fatty acids (LCPUFA) circulate in maternal plasma
      associated to lipoprotein triglycerides, and in a minor proportion in the form of
      FFA. Despite the lack of a direct placental transfer of triglycerides, diffusion
      of their fatty acids to the fetus is ensured by means of lipoprotein receptors,
      lipoprotein lipase activity and intracellular lipase activities in the placenta.
      Maternal plasma FFA are also an important source of LCPUFA to the fetus, and
      their placental uptake occurs via a selective process of facilitated membrane
      translocation involving a plasma membrane fatty acid-binding protein. This
      mechanism together with a selective cellular metabolism determine the actual rate
      of placental transfer and its selectivity, resulting even in an enrichment of
      certain LCPUFA in fetal circulation as compared to maternal. The degree to which
      the fetus is capable of fatty acid desaturation and elongation is not clear,
      although both term and preterm infants can synthesize LCPUFA from parental
      essential fatty acids. Nutritional status of the mother during gestation is
      related to fetal growth, and excessive dietary intake of certain LCPUFA has
      inhibitory effects on Delta-5- and Delta-6-desaturases. This inhibition causes
      major declines in arachidonic acid levels, as directly found in pregnant and
      lactating rats fed a fish oil-rich diet as compared to olive oil. An excess in
      dietary PUFA may also enhance peroxidation and reduce antioxidant capacity. Thus,
      since benefit to risks of modifying maternal fat intake in pregnancy and
      lactation are not yet completely established, additional studies are needed
      before recommendations to increase LCPUFA intake in pregnancy are made.

PMID- 11978056
TI  - The role of the placenta in fetal programming-a review.
AB  - The fetal origins hypothesis proposes that adult cardiovascular and metabolic
      disease originate through developmental plasticity and fetal adaptations arising
      from failure of the materno-placental supply of nutrients to match fetal
      requirements. The hypothesis is supported by experimental data in animals
      indicating that maternal nutrition can programme long term effects on the
      offspring without necessarily affecting size at birth. There is now evidence
      linking body composition in pregnant women and the balance of nutrient intake
      during pregnancy with raised levels of cardiovascular risk factors in the
      offspring. Maternal body composition and diet are thought to affect fetal
      development and programming as a result of both direct effects on substrate
      availability to the fetus and indirectly through changes in placental function
      and structure. Alterations in placental growth and vascular resistance, altered
      nutrient and hormone metabolism in the placenta, and changes in nutrient transfer
      and partitioning between mother, placenta and fetus all have important effects on
      the fetal adaptations thought to be central to programming. Future interventions
      to improve placental function are likely to have lifelong health benefits for the
      offspring.

PMID- 11978057
TI  - Placental regulation of fatty acid delivery and its effect on fetal growth--a
      review.
AB  - More than 90 per cent of the fat deposition in the fetus occurs in the last 10
      weeks of pregnancy during which it increases exponentially to reach a rate of
      accretion of around 7 g/day close to term. All of the n -3 and n -6 fatty acid
      structure acquired by the fetus has to cross the placenta and fetal blood is
      enriched in long chain polyunsaturated fatty acids (LCPUFA) relative to the
      maternal supply. The placenta may regulate its own fatty acid substrate supply
      via the action of placental leptin on maternal adipose tissue. Fatty acids cross
      the microvillous and basal membranes by simple diffusion and via the action of
      membrane bound and cytosolic fatty acid binding proteins (FABPs). The direction
      and magnitude of fatty acid flux is mainly dictated by the relative abundance of
      available binding sites. The fatty acid mix delivered to the fetus is largely
      determined by the fatty acid composition of the maternal blood although the
      placenta is able to preferentially transfer the important PUFA to the fetus as a
      result of selective uptake by the syncytiotrophoblast, intracellular metabolic
      channelling of individual fatty acids, and selective export to the fetal
      circulation. Placental FABP polymorphisms may affect these processes. There is
      little evidence to suggest that placental delivery of fatty acids limits normal
      fetal growth although the importance of the in utero supply may be to support
      post-natal development as most of the LCPUFA accumulated by the fetus is stored
      in the adipose tissue for use in early post-natal life.

PMID- 11978058
TI  - Regulation of placental transfer: the Na(+)/H(+) exchanger--a review.
AB  - This review article considers the purposes and mechanisms of regulation of
      placental transfer in general terms and then illustrates some key points with
      reference to the Na(+)/H(+) exchanger (NHE), a transport protein found in the
      syncytiotrophoblast. NHE probably has a role in the homeostasis of
      syncytiotrophoblast intracellular pH and may also be involved in
      syncytiotrophoblast cell volume regulation as well as H(+) loss from and Na(+)
      transfer to the fetus. The activity and expression of NHE in the microvillous
      plasma membrane of the syncytiotrophoblast is reduced in placentas from preterm,
      growth restricted babies as compared to their gestationally matched normally
      grown counterparts. There are differential effects of gestation in normal
      pregnancy on NHE mRNA, NHE protein and NHE activity. There is also evidence of
      acute modulation of NHE activity. Regulation of NHE in syncytiotrophoblast is
      therefore complex with control at transcription, post transcription and post
      translational loci.

PMID- 11978059
TI  - Adriana and Luisa Castellucci Award lecture 2001. Hypoxia inducible factor-1:
      oxygen regulation of trophoblast differentiation in normal and pre-eclamptic
      pregnancies--a review.
AB  - During early pregnancy, trophoblast differentiation occurs in an environment of
      relative low oxygen tension which is essential for normal embryonic and placental
      development. At around 10-12 weeks' gestation, when the intervillous space opens
      to maternal blood, there is an increase in Po(2). This increase correlates with
      the time of maximal trophoblast invasion into the maternal decidua, which allows
      extravillous trophoblast cells to access and remodel the maternal spiral
      arteries. Hypoxia Inducible Factor 1(HIF-1) is a transcription factor which
      activates gene transcription in response to varying oxygen concentration of
      cells. HIF-1 is a heterodimer composed of the inducible HIF-1alpha and the
      constitutively expressed HIF-1beta/ARNT subunits. Using villous explants, we have
      demonstrated that the oxygen-regulated events of early trophoblast
      differentiation are in part mediated by TGFbeta(3), an inhibitor of trophoblast
      differentiation, via HIF-1alpha. Pre-eclampsia is a disease of pregnancy that is
      characterized by shallow trophoblast invasion. Recently, we have reported that
      TGFbeta(3) is over-expressed in pre-eclamptic pregnancy and that its down
      regulation restores invasive capability to trophoblast cells. Because TGFbeta(3)
      is downstream of HIF-1alpha, in the present study we investigated the expression
      of HIF-1alpha in pre-eclamptic placentae and age-matched controls using in situ
      hybridization and histochemical analyses. We found that HIF-1alpha mRNA and
      protein expression are abnormally elevated in pre-eclamptic placental tissue when
      compared to normal placental tissue. We conclude that pre-eclampsia may result
      from a developmental failure of oxygen to increase or of trophoblast cells to
      respond and/or sense an increase in oxygen. This will prevent the normal TGFbeta3
      down-regulation and will lead to poor trophoblast invasion predisposing the
      pregnancy to pre-eclampsia.

PMID- 11978060
TI  - Mechanisms of oxygen sensing in human trophoblast cells.
AB  - During pregnancy, changes in oxygen tension are essential for proper embryonic
      and placental development. Little is known about the mechanisms underlying
      mammalian cellular adaptations to changes in oxygen tension. Currently, we have
      explored putative mechanisms by which human trophoblast cells may sense oxygen.
      In order to investigate a role for hemoproteins in oxygen sensing, we cultured
      human villous explants of 5-8 weeks gestation under 20 per cent O(2) in the
      presence of either cobalt chloride or desferrioxamine, which interfere with the
      ability of iron (heme) to interact with oxygen. Treatment with these compounds
      mimicked hypoxia by stimulating the low oxygen effect on extravillous trophoblast
      outgrowth (EVT) and inducing HIF-1alpha expression, analogous to that observed in
      explants cultured at 3 per cent O(2). Addition of unhindered iron, in the form of
      iron chloride, to the treated-explants reversed the stimulatory effect on EVT
      outgrowth and HIF-1alpha expression. Subsequently, in order to probe into a
      mitochondrial role in trophoblast oxygen sensing, we cultured first trimester
      villous explants under 3 per cent O(2) in the presence of either
      diphenyleneiodonium or rotenone, known inhibitors of flavin-containing proteins.
      Treated-explants showed inhibition of the typical low oxygen-induced EVT
      outgrowth, when compared to untreated controls. Thus, this data supports a
      hypothesis that trophoblast cells may utilize mitochondria and/or hemoproteins as
      oxygen sensors to detect the critical changes in oxygen tension during pregnancy.

PMID- 11978062
TI  - Pathogenesis of intrauterine growth restriction (IUGR)-conclusions derived from a
      European Union Biomed 2 Concerted Action project 'Importance of Oxygen Supply in
      Intrauterine Growth Restricted Pregnancies'-a workshop report.

PMID- 11978061
TI  - Cationic amino acid transporter activity in the syncytiotrophoblast microvillous
      plasma membrane and oxygenation of the uteroplacental unit.
AB  - The purpose of this study was to determine whether there is any relationship
      between the activity of cationic amino acid transporters in the microvillous
      plasma membrane (MVM) of the syncytiotrophoblast and the oxygenation of the
      uteroplacental unit. Oxygenation data were obtained at the time of caesarean
      section from the uterine veins, the maternal radial artery and the umbilical
      vessels of 7 normal (AGA) and 13 intrauterine growth restricted (IUGR)
      pregnancies. Microvillous plasma membranes were isolated from the same placentas
      and the activity of the system y(+) and y(+)L cationic amino acid transporters
      determined by measuring (3)H- l -arginine uptake in the presence and absence of l
      -glutamine. In IUGR pregnancies uterine venous Po(2) was significantly higher
      (AGA=44.7+/-8.0 mmHg; IUGR=57.2+/-2.3 mmHg, P< 0.05) and umbilical venous Po(2)
      was significantly lower (AGA=33.4+/-3.0 mmHg; IUGR=25.1+/-2.0 mmHg, P< 0.05) than
      in AGA pregnancies. System y(+)L activity, but not system y(+) activity, was
      inversely correlated with uterine venous Po(2) (P< 0.01; r(2)=0.4) in AGA and
      IUGR pregnancies. In IUGR pregnancies without associated maternal pre-eclampsia,
      y(+)L activity, but not y(+) activity, was also directly related to the umbilical
      O(2) content difference (P< 0.01; r(2)=0.9). A significant negative correlation
      was found between system y(+) and the umbilical O(2) content difference in AGA
      pregnancies (P< 0.01; r(2)=0.9). Our data are consistent with the hypothesis that
      in IUGR fetuses uterine oxygenation is not reduced and can be increased. The
      inverse correlation between system y(+)L activity and uterine venous Po(2) and
      the correlations with umbilical venous-arterial O(2) content difference suggest a
      relationship between cationic amino acid transporter activity and oxygen tension
      in the uteroplacental unit.

PMID- 11978063
TI  - Role of leptin in pregnancy--a review.
AB  - Leptin is an adipocyte-derived hormone that decreases food intake and body weight
      via its receptor in the hypothalamus. In rodents, it also modulates glucose
      metabolism by increasing insulin sensitivity. We previously reported that leptin
      is produced by human placental trophoblasts. We also revealed that leptin gene
      expression in the placenta was augmented in severe pre-eclampsia, and suggested
      that placental hypoxia may play a role in this augmentation. Maternal plasma
      leptin levels correlated well with mean blood pressure, but not with body mass
      index. Plasma leptin levels in pre-eclamptic women with IUGR were higher than
      those without IUGR (P< 0.05). We further examined the effects of hyperleptinemia
      on the course of pregnancy by using transgenic mice (Tg) overexpressing leptin.
      In pregnant Tg mice, food intake was significantly less than non-Tg, and the
      fetal body weights were reduced to approximately 70 per cent of those of non-Tg.
      Resistin is a novel adipocyte-derived hormone that decreases insulin sensitivity
      and increases plasma glucose concentration, thus contributing the development of
      obesity-related type II diabetes mellitus. We recently found that resistin gene
      is expressed in the human placenta as well as adipose tissue. In this review,
      possible roles of placental leptin and resistin are discussed.

PMID- 11978064
TI  - Human placental growth hormone--a review.
AB  - Placental growth hormone (PGH) is the product of the GH-V gene, predominantly
      expressed in the syncytiotrophoblast layer of the human placenta. PGH differs
      from pituitary growth hormone by 13 amino acids and possesses one glycosylation
      site. It has high somatogenic and low lactogenic activities. In the maternal
      circulation from 12-20 weeks up to term, PGH gradually replaces pituitary growth
      hormone, which becomes undetectable. PGH is secreted by the placenta in a non
      pulsatile manner. This continuous secretion appears to have important
      implications for physiological adjustment to gestation and especially in the
      control of maternal IGF1 levels. PGH secretion is regulated in vitro and in vivo
      by glucose. Lower maternal levels of PGH are observed in pregnancies with fetal
      growth retardation. PGH is one example of a trophoblast hormone, which allows
      maternal metabolic adaptation to pregnancy. In addition, our recent data on its
      expression in invasive extravillous trophoblasts suggest that the physiological
      role of PGH might also include a direct influence of this hormone on placental
      development via an autocrine or paracrine mechanism.

PMID- 11978065
TI  - B7 family molecules: novel immunomodulators at the maternal-fetal interface.
AB  - The placenta utilizes both active and passive mechanisms to evade rejection by
      the maternal immune system. Recently, the mRNA for two newly cloned members of
      the B7 family of immunomodulatory cell-associated proteins have been identified
      in the human term placenta. In this article, we review the current knowledge of
      the B7 family member B7-H1, and discuss how it may participate in modulation of
      the maternal immune system at the maternal-fetal interface. B7-H1 has been found
      to possess immunostimulatory or immunoinhibitory properties, and
      immunohistological examination of first trimester and term placenta has revealed
      that this protein is abundant in the placenta. B7-H1 is highly expressed by both
      the syncytiotrophoblast and extravillous cytotrophoblast, both of which lie in
      direct contact with maternal blood and tissue. Further, treatment of the
      choriocarcinoma cell line, JEG-3, with recombinant human interferon (IFN)-gamma
      resulted in a dose-dependent increase in the abundance of the message for B7-H1,
      suggesting that IFN-gamma could regulate expression of B7-H1 by the trophoblast.
      These studies document that the positioning of B7-H1 at the maternal-fetal
      interface is such that it could participate in suppression of activated maternal
      leukocytes.

PMID- 11978066
TI  - Inhibitory effects of human chorionic gonadotropin (hCG) preparations on HIV
      infection of human placenta in vitro.
AB  - Human chorionic gonadotropin (hCG) has been implicated in modifying Kaposi
      sarcoma lesions in HIV positive patients and in reducing HIV infection in human
      lymphocytes and human choriocarcinoma cells. These anti-HIV effects of hCG may
      contribute to the limited maternal to fetal transmission of HIV infection (25-35
      per cent without treatment). However, it is unknown whether such high dosages of
      hCG have any effect on vertical transmission of HIV or on the infection of the
      human placenta with cell-free HIV. We have investigated in a dose dependent
      manner the effects of hCG on HIV-1 infection of human term placentae. Using
      commercially available hCG preparations, the ability to modify the infection of
      placental explants in vitro was examined. Sigma hCG and ICN beta-hCG (0.1, 1, 10
      IU/ml) and APL hCG and Sigma and Serono recombinant hCG (0.1, 1, 10, 100 IU/ml)
      were added during 6 h of pre-incubation and the 4 days of culture (3 days
      following the 24 h exposure to HIV-1 Ba-L strain). Cell-free HIV infection of the
      placental explants was documented using DNA-PCR detection of Gag and LTR regions
      of HIV. Each experimental condition was repeated in different placentae (n=5) and
      each PCR amplification was performed in duplicate with each primer set
      (total=20). Our results demonstrate that there is a dose dependent inhibition of
      HIV-1 infection in the human placenta above the physiologic levels (0.2 IU/ml) of
      hCG produced during incubation. At the highest concentration used (100 IU/ml), 80
      per cent inhibition of HIV infection was achieved with urinary extract hCG and
      about 50 per cent with recombinant hCG. beta-hCG alone appears to possess an
      efficacy equivalent to the complete hCG molecule. In this in vitro study, hCG
      demonstrates specific anti-HIV inhibitory properties that cannot be solely
      attributed to urinary contamination of the commercial preparations. Such
      inhibitory action of hCG may be present at varying levels throughout gestation
      based upon the circulating levels of hCG and its production by the placenta.
      Knowledge of the specific mechanisms underlying this inhibition is necessary
      before clinical applications can be considered.

PMID- 11978067
TI  - Mechanisms of syncytial fusion: a review.
AB  - Syncytial fusion of trophoblast is a key process in placental morphogenesis and
      physiology. Disturbed syncytial fusion may lead to a number of pregnancy
      associated pathologies. The mechanisms regulating syncytial fusion are only
      partly understood. This review tries to summarize the available knowledge on
      trophoblast fusion, originating from different scientific disciplines. Among the
      themes addressed in this paper are: morphogenesis and functions of
      syncytiotrophoblast; early apoptotic events and changes in plasmalemmal
      phospholipid orientation; proteins involved in membrane fusion: ADAMs and
      retrovirally-derived proteins and short-lived proteolipid intermediates in
      membrane fusion. Deeper understanding of syncytiotrophoblast fusion in future
      studies is only to be anticipated from collaborative studies focusing in parallel
      on physicochemical events in the participating plasmalemmas, early
      apoptotic/differentiation events preceding the fusion and role of the fusogenic
      membrane proteins.

PMID- 11978068
TI  - In vitro models to study trophoblast function and dysfunction-- a workshop
      report.

PMID- 11978070
TI  - Umbilical cord and fetal growth--a workshop report.

PMID- 11978069
TI  - Placental development in normal and compromised pregnancies-- a review.
AB  - Intrauterine growth restriction (IUGR) is a significant cause of infant mortality
      and morbidity. It is now clear that IUGR infants exhibit higher rates of coronary
      heart disease, type 2-diabetes, hypertension and stroke as adults. Therefore,
      fetal growth not only impacts the outcome of the perinatal period, but also
      impacts adult well-being. The etiologies of IUGR are numerous, but are often
      associated with abnormalities in placental structure and function. The process of
      implantation and placentation requires the production of a plethora of growth
      factors, cell-adhesion molecules, extracellular matrix proteins, hormones and
      transcription factors. Many of these exhibit altered expression within the
      placenta of IUGR pregnancies. However, it has been difficult to fully assess
      their role during the development of placental insufficiency (PI) in the human,
      underscoring the need for animal models. Using an ovine model of PI-IUGR we have
      observed changes in the expression of vascular endothelial growth factor,
      placental growth factor, their common receptors, as well as angiopoietin 2 and
      its receptor, Tie 2. We found that changes in these growth factors can be
      associated with both acute and chronic changes in placental vascular structure
      and function. These studies and others are providing needed insight into the
      developmental chronology of placental insufficiency.

PMID- 11978071
TI  - Comparative biology of the vertebrate placenta--a workshop report.

PMID- 11978072
TI  - Placental-fetal interrelationship in IUGR fetuses--a review.
AB  - The role of placental function in maintaining an adequate fetal growth has been
      addressed by many different laboratories. The relationship between maternal and
      fetal circulation in the placenta is crucial for efficient exchanges of oxygen
      and nutrients. Moreover, maturational changes are taking place throughout
      gestation within the placenta in order to increase the transfer capacities while
      fetal/placental weight ratio is significantly decreasing. In human pregnancies,
      an impairment in the invasion of fetal trophoblast cells into the maternal
      decidua has been hypothesized as a cause of placental insufficiency leading to
      intrauterine growth restriction (IUGR). This condition has been associated with a
      number of adaptive changes taking place in both placenta and fetus. Adaptive
      changes can be followed by pathology leading to fetal death and therefore staging
      of the disease is fundamental for timing of delivery.A classification of the
      severity of IUGR in human pregnancies has been proposed based upon fetal heart
      rate (FHR) and Doppler velocimetry of the umbilical artery (pulsatility index or
      PI). This classification of clinical severity reflects different degrees of
      placental insufficiency and is associated with significant differences in
      placental nutrient exchange. Only those IUGR with pathological PI and FHR are
      associated with increasing degrees of hypoxemia and lacticacidemia. Furthermore,
      significant differences are observed in the transplacental glucose gradient in
      the most severe cases and the placental transport of essential amino acids is
      significantly reduced both in vivo and in vitro. These findings suggest that both
      placental metabolism and transport are altered in intrauterine growth restriction
      in humans.

PMID- 11978073
TI  - The role of the placenta in pre-eclampsia--a workshop report.

PMID- 11978074
TI  - Cytogenetics of placenta--a workshop report.

PMID- 11978075
TI  - Placenta and fetal membranes in human parturition and preterm delivery--a
      workshop report.

PMID- 11978076
TI  - Liver blood perfusion as a possible instrument for fetal growth regulation.
AB  - Placental and fetal liver blood perfusions are reduced in intrauterine growth
      restricted human fetuses. We hypothesized that changes in fetal liver blood
      supply can alter fetal growth. In nine ewes with twin pregnancies at a
      gestational age of 119+/-2 days, a stent (4 mm) was placed into the ductus
      venosus of one twin (DV(stent) group). Alternatively, in 17 near term sheep with
      twin (n=11) or singleton (n=6) pregnancies, a DV was blocked with an embolization
      coil (DV(coil) group) for about one week. The cell proliferation rate (pKi-67)
      was determined in the liver, heart, skeletal muscle, kidneys and placenta. The
      dilatation or occlusion of the DV did not change placental perfusion on the first
      day or later after surgery. The liver blood supply was decreased in the DV(stent)
      group by more than half from 499+/-371 to 278+/-219 ml min(-1) (mean+/-s.d.,
      n=4), and increased two-fold in the DV(coil) group (P< 0.05). The percentage of
      liver/body weight was decreased from 3.9+/-0.6 per cent in control twin to 3.0+/
      0.2 per cent (n=3) in the DV(stent) group. Occlusion of the DV lead to an
      increase in the percentage of liver/body weight from 3.4+/-0.8 per cent to 4.3+/
      0.8 per cent (n=11, P< 0.05). Reduced liver blood supply in the DV(stent) group
      was associated with a decrease of cell proliferation in the liver from 12.43+/
      2.31 to 6.5+/-0.62 (nuclei microm(2) 10(-4), n=3, P=0.058), in heart from 1.14+/
      0.03 to 0.93+/-0.02 (nuclei microm(2) 10(-4), P< 0.05), and in skeletal muscle
      from 0.82+/-0.05 to 0.54+/-0.01 (nuclei microm(2) 10(-4), P< 0.05). The increased
      liver blood perfusion following occlusion of the DV increased cell proliferation
      sixfold in the liver, (n=9, P< 0.005) and twofold in heart muscle, skeletal
      muscle and the kidneys (P< 0.05), whereas no significant difference was seen in
      the placenta. The expression of mRNA for IGF-I and IGF-II in the liver was
      increased in the DV(coil) group. In conclusion, these results suggest that liver
      blood perfusion can regulate fetal growth.

PMID- 11978077
TI  - Mechanisms of drug transfer across the human placenta-a workshop report.

PMID- 11978078
TI  - The complexities of leukocyte recruitment.

PMID- 11978079
TI  - Selectins: critical mediators of leukocyte recruitment.
AB  - Selectins are multi-functional adhesion molecules that mediate the initial
      interactions between circulating leukocytes and the endothelium. First identified
      over a decade ago, selectins have provided insight into areas as diverse as
      normal lymphocyte homing, leukocyte recruitment during inflammatory responses,
      carbohydrate ligand biosynthesis and adhesion-mediated signalling. This review
      will examine the selectins and their ligands with a focus on recent findings
      using knockout technology as well as the emerging role of selectins as signalling
      molecules.

PMID- 11978080
TI  - Chemokines in rapid leukocyte adhesion triggering and migration.
AB  - Leukocyte subsets are recruited from the blood to lymphoid and non-lymphoid
      tissues via a multi-step process that involves distinct adhesive and activation
      steps. Chemokines, a family of chemotactic cytokines that signal through G
      protein-coupled receptors, play critical roles in regulating the leukocyte
      recruitment cascade. Chemokines can be transported and immobilized on the surface
      of vascular endothelial cells, where they activate leukocyte subsets expressing
      specific receptors. Activation signals induce firm adhesion of rolling leukocytes
      by rapidly upregulating integrin affinity and/or avidity. Chemokines can also
      direct migration of adherent cells across the endothelium, and control
      segregation of cells into specific microenvironments within tissues. The
      regulated expression of chemokines and their receptors is a critical determinant
      for homing of specialized lymphocyte subsets, and controls both tissue and
      inflammation-specific immune processes.

PMID- 11978081
TI  - From rolling to arrest on blood vessels: leukocyte tap dancing on endothelial
      integrin ligands and chemokines at sub-second contacts.
AB  - In order to extravasate the bloodstream at specific sites of inflammation or
      antigen presentation, circulating leukocytes must rapidly translate specific
      adhesive and stimulatory signals into firm adhesion. Leukocyte arrest is nearly
      exclusively mediated by integrin receptors. Recent in vitro and in vivo evidence
      suggests that specialized integrins support reversible tethers that slow down
      selectin-initiated rolling of leukocytes prior to their arrest. In situ
      activation of integrin avidity by ligand and chemokine signaling can take place
      within fractions of seconds, resulting either in augmented reversible adhesions
      or immediate arrest on the vascular endothelium. The ability of leukocyte
      integrins to rapidly respond to these in situ avidity modulators appears to
      depend on preformed affinity and clustering states, which are internally
      regulated by cytoskeletal constraints on integrin conformation and mobility. We
      discuss potential regulatory mechanisms by which a given set of chemokine
      receptors and integrins may interact to rapidly generate high avidity, shear
      resistant integrin-mediated leukocyte arrest on vascular endothelium.

PMID- 11978082
TI  - Leukocyte transendothelial migration: a junctional affair.
AB  - A critical function of the inflammatory response is delivery of leukocytes to a
      site of injury, immune reaction or infection. Considerable information is
      available concerning the molecular mechanisms that capture flowing leukocytes and
      initiate their stable arrest on the lumenal surface of the blood vessel wall. In
      comparison, much less is known about the subsequent step(s) in migration of
      circulating blood leukocytes across endothelial cell-to-cell lateral borders to
      underlying tissues. This article will focus on the endothelial-dependent
      processes that coordinate transmigrations in peripheral vasculature during the
      inflammatory response.

PMID- 11978083
TI  - Integrin-dependent neutrophil migration in extravascular tissue.
AB  - Leukocyte recruitment to sites of injury or infection involves sequential
      interactions with endothelium and extravascular tissue components. While the
      intravascular events in this process have been extensively studied, the
      mechanisms regulating subsequent passage through the surrounding tissue are less
      well characterized. The migrating white blood cells need to establish transient
      and dynamic adhesive contacts with extracellular matrix proteins. Integrin
      receptors expressed on the leukocyte surface play a central role in these
      interactions, mediating linkages between the cytoskeloton and the external
      environment. This chapter focuses on roles of integrin molecules in neutrophil
      locomotion and the adhesive mechanisms that govern the motility of these cells in
      the extravascular tissue.

PMID- 11978084
TI  - Molecular mechanisms of neutrophil recruitment elicited by bacteria in the lungs.
AB  - The recruitment of leukocytes to an extravascular destination requires
      intercellular communication between tissue cells and leukocytes. The molecules
      mediating this intercellular communication play differing roles in recruiting
      different types of leukocytes, in response to different stimuli, in different
      tissues, and in different hosts. The present communication reviews the adhesion
      molecules, chemokines, other cytokines, and NF- kappa B proteins which regulate
      the recruitment of neutrophils elicited by bacteria in the lungs.

PMID- 11978085
TI  - Clinical overview of leukocyte adhesion and migration: where are we now?
AB  - This article discusses the potential for clinical translation of the large amount
      of information on the molecular basis of leukocyte-endothelial cell interactions
      that has been collected over the last twenty years. Areas of current interest
      include the identification of adhesion molecule expression in inflammation by
      diagnostic imaging, understanding variability in inflammatory responsiveness and
      disease susceptibility through identification of adhesion molecule and chemokine
      polymorphisms and the application to the treatment of inflammatory diseases of
      monoclonal antibodies and conventional drugs with specific actions on leukocyte
      adhesion and migration.

PMID- 11978087
TI  - Multiple reactions of triphenylstannane with Ru(5)(CO)(12)(C(6)H(6))(mu(5)-C)
      yield bimetallic clusters with unusually large numbers of tin ligands.
AB  - The cluster complex Ru(5)(CO)(12)(C(6)H(6))(mu(5)-C), 1, undergoes multiple
      addition reactions with Ph(3)SnH to yield two new bimetallic cluster complexes:
      Ru(5)(CO)(8)(mu-SnPh(2))(4)(C(6)H(6))(mu(5)-C), 2, 2% yield, and Ru(5)(CO)(7)(mu
      SnPh(2))(4)(SnPh(3))(C(6)H(6))(mu(5)-C)(mu-H), 3, 26% yield, containing four and
      five tin ligands, respectively. Both compounds consist of a square pyramidal
      Ru(5) cluster with an interstitial carbido ligand and bridging SnPh(2) groups
      located across each of the four edges of the base of the Ru(5) square pyramid.
      Compound 3 contains an additional SnPh(3) group terminally coordinated to one of
      the ruthenium atoms in the square base.

PMID- 11978088
TI  - Hydrothermal synthesis and structure of a new one-dimensional, mixed-metal U(VI)
      iodate, Cs(2)[(UO(2))(CrO(4))(IO(3))(2)].
AB  - The reaction of the molecular transition metal iodate, Cs[CrO(3)(IO(3))], with
      UO(3) under mild hydrothermal conditions provides access to a new low
      dimensional, mixed-metal U(VI) compound, Cs(2)[(UO(2))(CrO(4))(IO(3))(2)] (1).
      The structure of 1 is quite unusual and consists of one-dimensional
      (1)(infinity)[(UO(2))(CrO(4))(IO(3))(2)](2-) ribbons separated by Cs(+) cations.
      These ribbons are formed from [UO(7)] pentagonal bipyramids that contain a uranyl
      core, [CrO(4)] tetrahedra, and both monodentate and bridging iodate anions.
      Crystallographic data: 1, monoclinic, space group P2(1)/n, a = 7.3929(5) A, b =
      8.1346(6) A, c = 22.126(2) A, beta = 90.647(1) degrees, Z = 4 (T = 193 K).

PMID- 11978089
TI  - Oxygen reactivity of a nickel(II)-polyoximate complex.
AB  - The ligand tris(2-hydroxyiminopropyl)amine (Ox(3)H(3)) binds to nickel(II) in
      multiple protonation states. In the neutral state, the X-ray crystal structure of
      the monomeric complex [Ni(Ox(3)H(3))(NO(3))(H(2)O)](NO(3)).(H(2)O), 1, has six
      coordinate pseudo-octahedral geometry, with binding of the amine and three oxime
      nitrogens, a nitrate, and a water. In the mono-deprotonated form, the X-ray
      crystal structure shows a dimer, [Ni(Ox(3)H(2))(CH(3)CN)](2)(ClO(4))(2), 2, which
      has bridging oximate groups and a Ni-Ni distance of 3.575 A. The fully
      deprotonated complex, 3, shows significantly low Ni(II) oxidation potentials at 
      390 and +165 mV (versus Fc(+)/Fc). Complex 3 shows reactivity when exposed to
      O(2), consuming multiple O(2) equivalents and turning from the purple 3 to a dark
      brown complex, 4. Complex 4 has an EPR spectrum consistent with Ni(III), but spin
      quantitation accounts for only about 10% of the total Ni, consistent with
      turnover of the Ni oxidation states. This Ni(II)/O(2) system oxidizes
      triphenylphosphine to its oxide, with incorporation of the isotopic label from
      O(2).

PMID- 11978090
TI  - Single crystal structure determination of a new zirconium N-ethylpyridinium
      phosphonate: Zr(O(3)PCH(2)CH(2)NC(5)H(5))(F(-))(3).
AB  - We describe the structure of a new zirconium N-ethylpyridinium phosphonate,
      Zr(O(3)PCH(2)CH(2)NC(5)H(5))(F(-))(3), that has been determined by single-crystal
      X-ray analysis (monoclinic, P2(1)/c (No. 14), a = 12.3634(12) A, b = 9.3090(17)
      A, c = 9.8077(13) A, beta = 112.819(8) degrees, V = 1040.4(3) A(3), Z = 4). This
      structure is unlike any other reported zirconium phosphonate. Octahedral
      coordination about zirconium is completed by three oxygen atoms of three
      different phosphonate groups and three fluoride ligands. The structure is
      composed of corrugated infinite layers of these Zr octahedra that corner share
      their three oxygen atoms with the phosphonate tetrahedra. The appended cationic
      pyridinium groups lie between the inorganic sheets and are charge-balanced by the
      [Zr(O(3)P-)(3)F(3)](-) octahedra. This structure represents a new example of the
      structure-directing influence of cationic organic ligands on the zirconium
      phosphonate framework.

PMID- 11978091
TI  - New insights into the effects of self-association of the cation
      [Au[C(NHMe)(2)](2)](+) on its solid state structure and luminescence.
AB  - Colorless [Au[C(NHMe)(2)](2)]X.H(2)O (X = Cl or Br) crystallize as dimers with
      Au.Au separations of 3.1231(3) A (Cl salt) and 3.1297(4) A (Br salt) between the
      linear, two-coordinate cations, and there is no direct interaction of Au(I) with
      the halide ions which are hydrogen bonded to ligand N-H groups and the water
      molecules. The luminescence of these dimers occurs at higher energy than that
      observed in extended chains of the same cation in the corresponding (PF(6))(-)
      and (BF(4))(-) salts and shows the important effects of aggregation on the
      observed luminescence.

PMID- 11978092
TI  - Low-temperature synthesis of uranium tetraboride by solid-state metathesis
      reactions.
AB  - A novel synthesis of uranium tetraboride (UB(4)) by solid-state metathesis
      reaction is demonstrated. This approach significantly lowers the temperature
      required to synthesize this material to < or = 850 degrees C. When UCl(4) is
      reacted with 2 equiv of MgB(2) at 850 degrees C, crystalline UB(4) is formed.
      Powder X-ray diffraction and ICP-AES data support the reduction of UCl(4) to
      UCl(3) as the initial step in the reaction. The UB(4) product is purified by
      washing with water.

PMID- 11978093
TI  - Metal carboxylate-phosphonate hybrid layered compounds: synthesis and single
      crystal structures of novel divalent metal complexes with N
      (phosphonomethyl)iminodiacetic acid.
AB  - Two novel divalent metal complexes with N-(phosphonomethyl)iminodiacetic acid,
      H(2)O(3)PCH(2)N(CH(2)CO(2)H)(2) (H(4)PMIDA), [Co(2)(PMIDA)(H(2)O)(5)] x H(2)O, 1,
      and [Zn(2)(PMIDA)(CH(3)CO(2)H)] x 2H(2)O, 2, have been synthesized and
      structurally characterized. The structure of complex 1 features two different
      kinds of Co(II) layers, namely, a cobalt phosphonate layer along the <100> plane
      and a cobalt carboxylate layer along the <300> plane. The Co(II) atoms in the
      phosphonate layer are octahedrally coordinated by 4 aqua ligands and 2 oxygen
      atoms from two phosphonic acid groups. Two Co(II) octahedra are bridged by a pair
      of phosphonic groups into a dimeric unit, and such dimers are interconnected into
      a layer through hydrogen bonding between aqua ligands. The Co(II) atoms in the
      carboxylate layer are octahedrally coordinated by a chelating PMIDA ligand, one
      aqua ligand, and one phosphonic oxygen atom from the neighboring PMIDA ligand.
      These Co(II) octahedra are interlinked by bridging carboxylic groups into a one
      dimensional chain along the c-axis; such chains are held together by hydrogen
      bonds formed between carboxylic oxygen atoms and lattice water molecules, in such
      a way as to form a layer along the <300> direction. Two such layers are
      interconnected into a double layer via hydrogen bonding. These double layers are
      further interconnected with the Co(II) phosphonate layers through phosphonate
      tetrahedra along the a direction, resulting in the formation of a complicated
      three-dimensional network. The crystal structure of 2 contains a metal
      phosphonate and metal carboxylate hybrid layer along the <202> plane. One of the
      two zinc atoms in the asymmetric unit is tetrahedrally coordinated by four oxygen
      atoms from two phosphonic acid groups and two carboxylic groups; the other zinc
      atom is 5-coordinated by three oxygen atoms and a nitrogen atom from a chelating
      PMIDA ligand and one oxygen atom from the acetic acid. The above two types of
      zinc metal ions are interconnected by bridging carboxylic and phosphonic groups,
      resulting in the formation of a layered structure.

PMID- 11978094
TI  - Complexes formed between nitrilotris(methylenephosphonic acid) and M(2+)
      transition metals: isostructural organic-inorganic hybrids.
AB  - Nitrilotris(methylenephosphonic acid) (NTP, [N(CH(2)PO(3)H(2))(3)]) recently has
      been found to form three-dimensional porous structures with encapsulation of
      templates as well as layered and linear structures with template intercalation.
      It was, therefore, of interest to examine the type of organic-inorganic hybrids
      that would form with metal cations. Mn(II) was found to replace two of the six
      acid protons, while a third proton bonds to the nitrilo nitrogen, forming a
      zwitter ion. Two types of compounds were obtained. When the ratio of acid to
      Mn(II) was less than 10, a trihydrate, Mn[HN(CH(2)PO(3)H)(3)(H(2)O)(3)] (2)
      formed. Compound 2 is monoclinic P2(1)/c, with a = 9.283(2) A, b = 16.027(3) A, c
      = 9.7742(2) A, beta = 115.209(3) degrees, V = 1315.0(5) A(3), and Z = 4. The Mn
      atoms form zigzag chains bridged by two of the three phosphonate groups. The
      third phosphonate group is only involved in hydrogen bonding. The metal atoms are
      octahedrally coordinated with three of the sites occupied by water molecules.
      Adjacent chains are hydrogen-bonded to each other through POH and HN donors, and
      the additional participation of all the water hydrogens in H-bonding results in a
      corrugated sheet-like structure. Use of excess NTP at a ratio to metal of 10 to 1
      yields an anhydrous compound Mn[HN(CH(2)PO(3)H)(3)] (1), P2(1)/n, a = 9.129(1) A,
      b = 8.408(1) A, c = 13.453(1) A, beta = 97.830(2) degrees, V = 1023.0(2) A(3),
      and Z = 4. Manganese is five coordinate forming a distorted square pyramid with
      oxygens from five different phosphonate groups. The sixth oxygen is 2.85 A from
      an adjacent Mn, preventing octahedral coordination. All the protonated atoms,
      three phosphonate oxygens and N, form moderately strong hydrogen bonds in a
      compact three-dimensional structure. The open-structured trihydrate forms a
      series of isostructural compounds with other divalent transition metal ions as
      well as with mixed-metal compositions. This is indicative that the hydrogen
      bonding controls the type of structure formed irrespective of the cation.

PMID- 11978095
TI  - Synthesis, characterization, and crystal structures of two divalent metal
      diphosphonates with a layered and a 3D network structure.
AB  - Reactions of N-methyliminobis(methylenephosphonic acid),
      CH(3)N(CH(2)PO(3)H(2))(2) (H(4)L), with divalent metal acetates under different
      conditions result in metal diphosphonates with different structures.
      Mn(H(3)L)(2).2H(2)O (complex 1) with a layer structure was prepared by a layering
      technique. It is triclinic, P1 macro with a = 9.224(3) A, b = 9.780(3) A, c =
      10.554(3) A, alpha = 82.009(6) degrees, beta = 74.356(6) degrees, gamma =
      89.853(6) degrees, Z = 2. The Mn(II) ion is octahedrally coordinated by six
      phosphonate oxygen atoms from four ligands, two of them in a bidentate and two in
      a unidentate fashion. Each MnO(6) octahedron is further linked to four
      neighboring MnO(6) octahedra through four bridging phosphonate groups, resulting
      in a two-dimensional metal phosphonate (002) layer. These layers are held
      together by strong hydrogen bonds between uncoordinated phosphonate oxygen atoms.
      The zinc complex Zn(3)(HL)(2) (complex 2) was synthesized by hydrothermal
      reactions (4 days, 438 K, autogenous pressure). It is monoclinic, P2(1)/n with a
      = 7.7788(9) A, b = 17.025(2) A, c = 13.041(2) A, beta = 94.597(2) degrees, Z = 4.
      The structure of complex 2 features a 3D network built from ZnO(4) tetrahedra
      linked together by bridging phosphonate groups. Each zinc cation is tetrahedrally
      coordinated by four phosphonate oxygen atoms from four ligands, each of which
      connects with six zinc atoms, resulting in voids of various sizes. Magnetic
      measurements for the manganese complex shows an antiferromagnetic interaction at
      low temperature. The effect of the extent of deprotonation of phosphonic acids on
      the type of complex formed is discussed.

PMID- 11978096
TI  - Magnetic coupling and intermetallic electron transfer in the heterodinuclear
      bioctahedral complexes MW(III)Cl(9)(n-) (M = V(II), Cr(III), Mn(IV)): tweaking
      the balance between ferromagnetism and antiferromagnetism.
AB  - Density functional theory (DFT) calculations have been used to investigate the
      effect of intermetallic electron transfer on the mode of magnetic coupling in the
      face-shared bimetallic complexes MWCl(9)(n-) (M = V, Cr, Mn; all with a nominal
      d(3) valence electronic configuration on each metal atom). These calculations
      illustrate a simple rule: when the oxidation state of M is lower than that of W,
      antiferromagnetic coupling is preferred, while ferromagnetism (via crossed
      exchange pathways) is favored when M has the higher oxidation state. This
      underlying trend in intermetallic interactions is seen to depend on the interplay
      among ligand field splitting, spin polarization splitting of alpha- and beta-spin
      orbitals, and the relative energies of the M and W valence d orbitals, and is
      mirrored in the results seen in a wider survey of mixed-metal, face-shared
      complexes.

PMID- 11978097
TI  - Dinuclear rhodium and iridium complexes with mixed amido/methoxo and
      amido/hydroxo bridges.
AB  - The reactions of [[M(mu-OMe)(cod)](2)] (M = Rh, Ir; cod = 1,5- cyclooctadiene)
      with p-tolylamine, alpha-naphthylamine, and p-nitroaniline gave complexes with
      mixed-bridging ligands, [[M(cod)](2)(mu-NHAr)(mu-OMe)]. Similarly, the related
      complexes [[Rh(cod)](2)(mu-NHAr)(mu-OH)] were prepared from the reactions of
      [[Rh(mu-OH)(cod)](2)] with p-tolylamine, alpha-naphthylamine, and p-nitroaniline.
      The reactions of [[Rh(mu-OR)(cod)](2)] (R = H, Me) with o-nitroaniline gave the
      mononuclear complex [Rh(o-NO(2)C(6)H(4)NH)(cod)]. The syntheses of the amido
      complexes involve a proton exchange reaction from the amines to the methoxo or
      hydroxo ligands and the coordination of the amide ligand. These reactions were
      found to be reversible for the dinuclear complexes. The structure of
      [[Rh(cod)](2)(mu-NH[p-NO(2)C(6)H(4)])(mu-OMe)] shows two edge-shared square
      planar rhodium centers folded at the edge with an anti configuration of the
      bridging ligands. The complex [[Rh(cod)](2)(mu-NH[alpha-naphthyl])(mu-OH)]
      cocrystallizes with [[Rh(mu-OH)(cod)](2)] and THF, forming a supramolecular
      aggregate supported by five hydrogen bridges in the solid state. In the
      mononuclear [Rh(o-NO(2)C(6)H(4)NH)(cod)] complex the o-nitroamido ligand chelates
      the rhodium center through the amido nitrogen and an oxygen of the nitro group.

PMID- 11978099
TI  - Lattice potential energy estimation for complex ionic salts from density
      measurements.
AB  - This paper is one of a series exploring simple approaches for the estimation of
      lattice energy of ionic materials, avoiding elaborate computation. The readily
      accessible, frequently reported, and easily measurable (requiring only small
      quantities of inorganic material) property of density, rho(m), is related, as a
      rectilinear function of the form (rho(m)/M(m))(1/3), to the lattice energy U(POT)
      of ionic materials, where M(m) is the chemical formula mass. Dependence on the
      cube root is particularly advantageous because this considerably lowers the
      effects of any experimental errors in the density measurement used. The
      relationship that is developed arises from the dependence (previously reported in
      Jenkins, H. D. B.; Roobottom, H. K.; Passmore, J.; Glasser, L. Inorg. Chem. 1999,
      38, 3609) of lattice energy on the inverse cube root of the molar volume. These
      latest equations have the form U(POT)/kJ mol(-1) = gamma(rho(m)/M(m))(1/3) +
      delta, where for the simpler salts (i.e., U(POT)/kJ mol(-1) < 5000 kJ mol(-1)),
      gamma and delta are coefficients dependent upon the stoichiometry of the
      inorganic material, and for materials for which U(POT)/kJ mol(-1) > 5000,
      gamma/kJ mol(-1) cm = 10(-7) AI(2IN(A))(1/3) and delta/kJ mol(-1) = 0 where A is
      the general electrostatic conversion factor (A = 121.4 kJ mol(-1)), I is the
      ionic strength = 1/2 the sum of n(i)z(i)(2), and N(A) is Avogadro's constant.

PMID- 11978098
TI  - Apical versus equatorial disposition of substituents in tetraoxyphosphoranes
      bearing a 1,3,2-dioxaphosphocin ring: implications on apicophilicity in trigonal
      bipyramidal phosphorus.
AB  - New spirocyclic (amino/amido)tetraoxyphosphoranes CH(2)(6-t-Bu-4-Me
      C(6)H(2)O)(2)P(NRR')(O(2)C(6)Cl(4)) [R = Me, R' = Ph (1), R = R' = i-Pr (2); R =
      R' = H (3); R = H, R' = Ph (4)] and the isothiocyanatotetraoxyphosphorane CH(2)(6
      t-Bu-4-Me-C(6)H(2)O)(2)P(NCS)(O(2)C(6)Cl(4)) (5) have been synthesized. X-ray
      crystallography for these compounds reveals that -N(Me)Ph, -N(i-Pr)(2), and -NCS
      groups occupy an apical position whereas -NH(2) and -NHPh groups occupy an
      equatorial position in a trigonal bipyramidal geometry around phosphorus. These
      results are in contrast with the common assumption that a sterically bulky and
      less electronegative substituent [e.g. -N(i-Pr)(2)] should be less apicophilic
      than a sterically small and more electronegative substituent (e.g. -NH(2)). The
      possible rationalization for these results is discussed. Variable-temperature
      ((1)H, (31)P) NMR spectra of these compounds show some unusual features not
      reported before for pentacoordinate phosphorus. Probable intramolecular processes
      involving (i) apical-equatorial <--> equatorial-apical exchange, (ii) apical
      equatorial <--> equatorial-equatorial exchange, and (iii) boat-chair <--> tub
      (for the eight-membered ring) interconversion as well as cessation of the P-N
      bond rotation have been invoked to explain the spectral features.

PMID- 11978100
TI  - Thermodynamic and kinetic control over the reduction mechanism of the
      Pd(3)(dppm)(3)(CO)(I)(+) cluster.
AB  - The reduction mechanism of the title cluster has been investigated by means of
      cyclic voltammetry (CV), rotating disk electrode (RDE) voltammetry, and
      coulometry. The 2-electron reduction proceeds via two routes simultaneously. The
      first one involves two 1-electron reduction steps, followed by an iodide
      elimination to form the neutral Pd(3)(dppm)(3)(CO)(0) cluster (EEC mechanism).
      The second one is a 1-electron reduction process, followed by an iodide
      elimination, then by a second 1-electron step (ECE mechanism) to generate the
      same final product. Control over these two competitive mechanisms can be achieved
      by changing temperature, solvent polarity, iodide concentration, or sweep rate.
      The reoxidation of the Pd(3)(dppm)(3)(CO)(0) cluster in the presence of iodide
      proceeds via a pure ECE pathway. The overall results were interpreted with a six
      member square scheme, and the cyclic and RDE voltammograms were simulated, in
      order to extract the reaction rate and equilibrium constants for iodide exchange
      for all three Pd(3)(dppm)(3)(CO)(I)(n)() (n = +1, 0, -1) adducts.

PMID- 11978101
TI  - Reactions of AlH(3) x NMe(3) with nitriles: structural characterization and
      substitution reactions of hexameric aluminum imides.
AB  - The reaction of AlH(3).NMe(3) with RCN proceeds with the evolution of
      trimethylamine and affords (HAINCH(2)R)(6) (R = Ph (1), p-MeC(6)H(4) (2), p
      CF(3)C(6)H(4) (3)). Compounds 1 and 3 are characterized by single-crystal
      structural analysis. Compound 1 reacts with Me(3)SiBr as well as with PhC[triple
      bond]CH to give (XAINCH(2)Ph)(6) (X = Br (4), PhC[triple bond]C (5)). Structural
      data and other characterization data of compounds 4 and 5 show that all the
      hydridic hydrogen atoms in 1 have been replaced by bromine atoms and PhC[triple
      bond]C groups, respectively. Compounds 1-5 are potential precursors for the
      preparation of aluminum nitride. Crystals of 1 are rhombohedral, space group R3
      macro, with a = 15.7457(13) A, b = 15.7457(13) A, c = 14.949(2) A, V = 3209.8(5)
      A(3), and Z = 3. Crystals of 3.(3)/(4)C(7)H(8) are triclinic, space group P1
      macro, with a = 17.527(11) A, b = 18.894(12) A, c = 19.246(15) A, alpha =
      96.11(7) degrees, beta = 102.23(4) degrees, gamma = 106.79(3) degrees, V =
      5867(7) A(3), and Z = 4. Compound 4 crystallizes in the monoclinic space group
      P2(1)/c, with a = 14.175(4) A, b = 16.678(5) A, c = 10.731(3) A, beta = 106.82(2)
      degrees, V = 2428.6(11) A(3), and Z = 2. Compound 5. C(7)H(8) crystallizes in the
      monoclinic space group C2/c, with a = 25.842(5) A, b = 15.443(3) A, c = 20.699(4)
      A, beta = 105.88(3) degrees, V = 7945(3) A(3), and Z = 4.

PMID- 11978102
TI  - Thiofunctional vanadium complexes.
AB  - The neutral tetradentate ligand 1,6-bis(2'-pyridyl)-2,5-dithiahexane (N(2)S(2)),
      containing two thioether functions, reacts with [VX(2)L(4)] (X = Br, L(4) = 2
      tmeda (tmeda = Me(2)NCH(2)CH(2)NMe(2)); X = I, L = tetrahydrofuran (THF)) and
      [VX(3)(THF)(3)] (X = Br, I) to form the complexes [VX(2)(N(2)S(2))] (1) and
      [VX(2)(N(2)S(2))]X (2), respectively. [V(2)(mu-Cl)(3)(THF)(6)]I and N(2)S(2)
      yield the V(IV) complex [VOCl(N(2)S(2)]I (3). The pentadentate, dianionic ligand
      2,6-bis(2'-mercaptophenylthio)dimethylpyridine, NS(2)S'(2)(2-), which contains
      two thioether (S) and two thiophenolate (S') functions, reacts with
      [VBr(3)(THF)(3)] to afford [VBr(NS(2)S'(2))] (4). The complex [VO(Cl)S'NS'] (5;
      H(2)S'NS' is the Schiff base formed between o-mercaptoaniline and o
      mercaptobenzaldehyde) is obtained by redox interaction between [VCl(3)(THF)(3)]
      and 2,2'-dithiodibenzaldehyde in the presence of o-mercaptoaniline. The crystal
      and molecular structures have been obtained for 3. THF, 4. THF, and 5. n
      C(5)H(12). The relevance of these compounds and their formation for the
      interaction between vanadium and thiofunctional biomolecules is addressed.

PMID- 11978103
TI  - Synthesis and molecular structure of [[(HBpz(3))Rh(PPh(3))(mu-Cl)(2)](2)Ag]BF(4)
      (Hpz = pyrazole), a heterotrinuclear Rh(2)Ag compound with square-planar
      silver(I).
AB  - Reaction of [(HBpz(3))RhCl(2)(PPh(3))] (Hpz = pyrazole) with silver salts AgA (A
      = BF(4), NO(3), SbF(6)) affords the unexpected heterotrinuclear compounds
      [[(HBpz(3))Rh(PPh(3))(mu-Cl)(2)](2)Ag]A (A = BF(4) (1), NO(3) (2), SbF(6) (3)).
      The compounds have been fully characterized by IR, (1)H, (31)P[(1)H], and
      (13)C[(1)H] NMR spectroscopy and FAB(+) mass spectrometry. The solid structure of
      compound 1 was determined by single-crystal X-ray diffraction. The cation
      consists of two (HBpz(3))RhCl(2)(PPh(3)) units bonded to a silver atom through
      two double mu-Cl bridges in an unusual distorted square-planar arrangement.

PMID- 11978104
TI  - Structural and density functional studies of uranium(III) and lanthanum(III)
      complexes with a neutral tripodal N-donor ligand suggesting the presence of a U-N
      back-bonding interaction.
AB  - The crystal structures of two trisiodide octacoordinated uranium(III) complexes
      of tris[(2-pyrazinyl)methyl]amine (tpza), which differ only by the ligand
      occupying the eighth coordination site (thf or MeCN), and of their lanthanum(III)
      analogues have been determined. In the acetonitrile adducts the M-N(pyrazine)
      distances are very similar for U(III) and La(III), while the U-N(acetonitrile)
      distance is 0.05 A shorter than the La-N(acetonitrile) distance. In the
      [M(tpza)I(3)(thf)] complexes in which the monodentate acetonitrile ligand, a weak
      pi-acceptor ligand, is replaced by a thf molecule, a sigma-donor only, the mean
      value of the distance U-N(pyrazine) is 0.05 A shorter than the mean value of the
      La-N(pyrazine) distance. Since we are comparing isostructural compounds of ions
      with very similar ionic radii, these differences indicate the presence of a
      stronger M-N interaction in the U(III) complexes and therefore suggest the
      presence of a covalent contribution to the U-N bonding. The selectivity of the
      tpza ligand toward U(III) complexation (with respect to that of La(III)) in the
      presence of sigma-donor-only ligands has been quantified by the value of
      K(U(tpza))/K(La(tpza)) measured to be 3.3 +/- 0.5. The analysis of the metal-N
      donor ligand bonding was carried out by a quasi-relativistic density functional
      theory study on small model compounds, of formula I(3)M-L (M = La, Nd, U; L =
      acetonitrile, pyrazine) and I(3)M-(pyrazine)(3) (M = La, U). The structural data
      obtained from geometry optimizations on these systems reproduce experimental
      trends, i.e., a decrease in the M-N distance from La to U, combined with an
      increase of the C-N distance in the acetonitrile derivatives. A detailed orbital
      analysis carried out on the resulting optimized complexes did not reveal any
      orbital interaction between the trivalent lanthanide cations (Ln(3+)) and the N
      donor ligands. In contrast, a back-donation electron transfer from 5f U(3+)
      orbitals to the pi* virtual orbital of the ligand was observed for both
      acetonitrile and pyrazine. Evaluation of the total bonding energy between the
      MI(3) and L fragments shows that this orbital interaction leads to a
      stabilization of the uranium(III) system compared to the lanthanide species.

PMID- 11978105
TI  - Low-temperature UV-visible and NMR spectroscopic investigations of O(2) binding
      to ((6)L)Fe(II), a ferrous heme bearing covalently tethered axial pyridine
      ligands.
AB  - In this report, we describe the reversible dioxygen reactivity of ((6)L)Fe(II)
      (1) [(6)L = partially fluorinated tetraphenylporphyrin with covalently appended
      TMPA moiety; TMPA = tris(2-pyridylmethyl)amine] using a combination of low
      temperature UV-vis and multinuclear ((1)H and (2)H) NMR spectroscopies. Complex
      1, or its pyrrole-deuterated analogue ((6)L-d(8))Fe(II) (1-d(8)), exhibits
      downfield shifted pyrrole resonances (delta 28-60 ppm) in all solvents utilized
      [CH(2)Cl(2), (CH(3))(2)C(O), CH(3)CN, THF], indicative of a five-coordinate high
      spin ferrous heme, even when there is no exogenous axial solvent ligand present
      (i.e., in methylene chloride). Furthermore, ((6)L)Fe(II) (1) exhibits non
      pyrrolic upfield and downfield shifted peaks in CH(2)Cl(2), (CH(3))(2)C(O), and
      CH(3)CN solvents, which we ascribed to resonances arising from the intra- or
      intermolecular binding of a TMPA-pyridyl arm to the ferrous heme. Upon exposure
      to dioxygen at 193 K in methylene chloride, ((6)L)Fe(II) (1) [UV-vis: lambda(max)
      = 433 (Soret), 529 (sh), 559 nm] reversibly forms a dioxygen adduct [UV-vis:
      lambda(max) = 422 (Soret), 542 nm], formulated as the six-coordinate low-spin
      [delta(pyrrole) 9.3 ppm, 193 K] heme-superoxo complex ((6)L)Fe(III)-(O(2)(-))
      (2). The coordination of the tethered pyridyl arm to the heme-superoxo complex as
      axial base ligand is suggested. In coordinating solvents such as THF, reversible
      oxygenation (193 K) of ((6)L)Fe(II) (1) [UV-vis: lambda(max) = 424 (Soret), 542
      nm] also occurs to give a similar adduct ((6)L)Fe(III)-(O(2)(-)) (2) [UV-vis:
      lambda(max) = 418 (Soret), 537 nm. (2)H NMR: delta(pyrrole) 8.9 ppm, 193 K].
      Here, we are unable to distinguish between a bound solvent ligand or tethered
      pyridyl arm as axial base ligand. In all solvents, the dioxygen adducts decompose
      (thermally) to the ferric-hydroxy complex ((6)L)Fe(III)-OH (3) [UV-vis:
      lambda(max) = 412-414 (Soret), 566-575 nm; approximately delta(pyrrole) 120 ppm
      at 193 K]. This study on the O(2)-binding chemistry of the heme-only homonuclear
      ((6)L)Fe(II) (1) system lays the foundation for a more complete understanding of
      the dioxygen reactivity of heterobinuclear heme-Cu complexes, such as
      [((6)L)Fe(II)Cu(I)](+), which are models for cytochrome c oxidase.

PMID- 11978106
TI  - Photochemical image generation in a cyanogel system synthesized from
      tetrachloropalladate(II) and the trimetallic mixed-valence complex [(NC)(5)Fe(II)
      CN-Pt(IV)(NH(3))(4)-NC-Fe(II)(CN)(5)](4-): consideration of photochemical and
      dark mechanistic pathways of Prussian blue formation.
AB  - The cyanogel system involving PdCl(4)(2-) and the mixed-valence complex
      [(NC)(5)Fe(II)-CN-Pt(IV)(NH(3))(4)-NC-Fe(II)(CN)(5)](4-) is reported. The system
      has been characterized by UV-vis absorption, diffuse reflectance infrared, and
      resonance Raman spectroscopies. Gelation occurs through coordination of Pd(II) to
      the nitrogen atom of terminal cyanide ligands in the mixed-valence complex.
      Irradiation into the Fe(II) --> Pt(IV) intervalent electron transfer (IT) band of
      [(NC)(5)Fe(II)-CN-Pt(IV)(NH(3))(4)-NC-Fe(II)(CN)(5)](4-) results in the formation
      of a variety of Prussian-blue-like species within the rigid cyanogel matrix.
      Photochemical and dark mechanisms involving coupled cyanide loss and Fe(II)
      oxidation are proposed for the formation of Prussian-blue-like species. The
      optical contrast between irradiated and nonirradiated regions of the gel enables
      photochemical image generation with at least 12 microm resolution. This
      capability is demonstrated through the production of a series of diffraction
      gratings in cyanogel samples.

PMID- 11978107
TI  - Crystal structure and spectroscopic properties of Na(2)K(6)(VO)(2)(SO(4))(7).
AB  - Red-brown crystals of a new mixed alkali oxo sulfato vanadium(V) compound
      Na(2)K(6)(VO)(2)(SO(4))(7), suitable for X-ray determination, have been obtained
      from the catalytically important binary molten salt system M(2)S(2)O(7)-V(2)O(5)
      (M = 80% K and 20% Na). By slow cooling of a mixture with the mole fraction
      X(V(2)O(5)) = 0.24 from 325 degrees C, i.e., just below the liquidus temperature,
      to the solidus temperature of around 300 degrees C, a dark reddish amorphous
      phase was obtained containing crystals of the earlier described V(V)-V(IV) mixed
      valence compound K(6)(VO)(4)(SO(4))(8) and Na(2)K(6)(VO)(2)(SO(4))(7) described
      here. This compound crystallizes in the tetragonal space group P4(3)2(1)2 (No.
      96) with a = 9.540(3) A, c = 29.551(5) A at 20 degrees C and Z = 4. It contains a
      distorted VO(6) octahedron with a short V-O bond of 1.552(6) A, a long one of
      2.276(5) A trans to this, and four equatorial V-O bonds in the range 1.881(6)
      1.960(6) A. The deformation of the VO(6) octahedron is less pronounced compared
      to that of the known oxo sulfato V(V) compounds. Each VO(3+) group is coordinated
      to five sulfate groups of which two are unidentately coordinated and three are
      bidentate bridging to neighboring VO(3+) groups. The length of the S-O bonds in
      the S-O-V bridges of the two unidentately coordinated sulfato groups are 1.551(6)
      A and 1.568(6) A, respectively, which are unusually long compared to our earlier
      measurements of sulfate groups in other V(III), V(IV), and V(V) compounds.

PMID- 11978108
TI  - Reactivity of [Re[kappa(3)-H(mu-H)B(tim(Me))(2)](CO)(3)] (tim(Me) = 2-mercapto-1
      methylimidazolyl) toward neutral substrates.
AB  - The complex [Re[kappa(3)-H(mu-H)B(tim(Me))(2)](CO)(3)] (2a) (tim(Me) = 2-mercapto
      1-methylimidazolyl) reacts with a variety of neutral substrates to afford new
      complexes featuring the dihydrobis(2-mercapto-1-methylimidazolyl)borate
      coordinated in a bidentate or unidentate fashion. By treating 2a with unidentate
      ligands, the mononuclear complexes [Re[kappa(2)-H(2)B(tim(Me))(2)](CO)(3)(L)] (L
      = imidazole (5), 4-(dimethylamino)pyridine (6), tert-butylisonitrile (7),
      triphenylphosphine (8)) were formed, upon replacement of the agostic B-H...Re
      bond by the correspondent unidentate ligand. With potentially bidentate
      substrates, 2a is transformed into mononuclear or dinuclear complexes, depending
      on the atom donor set of the reacting substrates. Reaction of compound 2a with
      ethylenediamine (en) gave the complex [Re[kappa(1)-H(2)B(tim(Me))(2)](CO)(3)(en)]
      (9), because of cleavage of the agostic interaction, dechelation of one
      mercaptoimidazolyl ring, and bidentate coordination of the amine. By contrast,
      1,2-bis(diphenyl)phosphinoethane (dppe) is not able to replace the
      mercaptoimidazolyl ring, and the dimer [Re[kappa(2)
      H(2)B(tim(Me))(2)](CO)(3)](2)(mu-dppe) (10) was formed. The novel Re(I)
      tricarbonyl complexes (5-10) have been fully characterized, including by X-ray
      diffraction analysis in the case of 6, 8, 9, and 10. The X-ray diffraction study
      confirmed the unprecedented unidentate coordination mode of the dihydrobis(2
      mercapto-1-methylimidazolyl)borate in complex 9.

PMID- 11978109
TI  - In(2)(OH)(3)(BDC)(1.5) (BDC = 1,4-benzendicarboxylate): an In(III) supramolecular
      3D framework with catalytic activity.
AB  - The new hybrid inorganic-organic polymer In(2)(OH)(3)[O(4)C(8)H(4)](1.5) has been
      hydrothermally obtained. Conditions for the synthesis are reported. The crystal
      structure of this material has been established by single-crystal X-ray
      diffraction: it is monoclinic, with space group P2(1)/c (Nomicron. 14), a =
      6.772(1) A, b = 10.329(2) A, c = 20.152(3) A, beta = 97.573(3) degrees. The In
      atoms are octahedrally coordinated by three hydroxide groups and three different
      molecules of carboxylate ligand. The resulting polymeric 3D structure can be
      envisaged as having been generated from a honeycomb (6,3) 2D that is cross-linked
      by the BDC organic anions. Data of IR and TGA-DTA studies, as well as the results
      of reduction of nitroaromatics and selective oxidation of organic sulfide
      reactions catalyzed by the new material, are reported.

PMID- 11978110
TI  - Synthesis, characterization, and reactivity of mononuclear O,N-chelated
      vanadium(IV) and -(III) complexes of methyl 2-Aminocyclopent-1-ene-1
      dithiocarboxylate based ligand: reporting an example of conformational isomerism
      in the solid state.
AB  - Vanadium(IV) and -(III) complexes of a tetradentate N(2)OS Schiff base ligand
      H(2)L [derived from methyl 2-((beta-aminoethyl)amino)cyclopent-1-ene-1
      dithiocarboxylate and salicylaldehyde] are reported. In all the complexes, the
      ligand acts in a bidentate (N,O) fashion leaving a part containing the N,S donor
      set uncoordinated. The oxovanadium(IV) complex [VO(HL)(2)] (1) is obtained by the
      reaction between [VO(acac)(2)] and H(2)L. In the solid state, compound 1 has two
      conformational isomers 1a and 1b; both have been characterized by X-ray
      crystallography. Compound 1a has the syn conformation that enforces the donor
      atoms around the metal center to adopt a distorted tbp structure (tau = 0.55).
      Isomer 1b on the other hand has an anti conformation with almost a regular square
      pyramidal geometry (tau = 0.06) around vanadium. In solution, however, 1 prefers
      to be in the square pyramidal form. A second variety of vanadyl complex
      [VO(L(cyclic))(2)](I(3))(2) (2) with a new bidentate O,N donor ligand involving
      isothiazolium moiety has been obtained by a ligand-based oxidation of the
      precursor complex 1 with iodine. Preliminary X-ray and FAB mass spectroscopic
      data of 2 have supported the formation of a heterocyclic moiety by a ring closure
      reaction involving a N-S bond. Vanadium(III) complex [V(acac)(HL)(2)] (3) has
      been obtained through partial ligand displacement of [V(acac)(3)] with H(2)L.
      Compound 3 has almost a regular octahedral structure completed by two bidentate
      HL ligands along with an acetylacetonate molecule. Electronic spectra, magnetism,
      EPR, and redox properties of these compounds are reported.

PMID- 11978112
TI  - Parahydrogen induced polarization and the oxidative addition of hydrogen to
      iridium tribromostannyl carbonylate anions.
AB  - Activation of dihydrogen by a system composed of (Bu(4)N)[IrBr(2)(CO)(2)] (1) and
      tin dibromide in varying ratios was studied using parahydrogen induced
      polarization (PHIP) which allows the detection of transient dihydrides not
      observable in conventional (1)H NMR spectra. While the oxidative addition of
      dihydrogen to neutral and cationic Ir(I) species is common, there are only a few
      examples of H(2) addition to anionic complexes. Tin dibromide reacts with
      iridium(I) complex 1 in acetone forming equilibrium mixtures of cis- and trans
      tribromostannyl derivatives [IrBr(n)()(SnBr(3))(2)(-)(n)()(CO)(2)](-), n = 0,1,
      the existence of which is inferred from the stereochemistries of the dihydrogen
      addition products determined using PHIP. The sigma-donating effect of the
      SnBr(3)(-) ligand facilitates the oxidative addition to the iridium center. The
      structures of the dihydrides formed upon addition of dihydrogen are assigned on
      the basis of hydride chemical shifts and values of (2)J((1)H-(117,119)Sn). The
      only dihydride observed in conventional (1)H NMR spectra is cis-trans-cis
      [IrH(2)(SnBr(3))(2)(CO)(2)](-), the identity of which was confirmed using the
      (13)C labeled Ir(I) precursor. Both [IrBr(2)(CO)(2)](-) and its tribromostannyl
      derivatives catalyze cis-pairwise addition of dihydrogen to phenylacetylene.

PMID- 11978111
TI  - Tetranuclear manganese complexes with dimer-of-dimer and ladder structures from
      the use of a bis-bipyridyl ligand.
AB  - The reaction of the bis-chelating ligand 1,2-bis(2,2'-bipyridine-6-yl)ethane (L)
      with the trinuclear species of formula [Mn(3)O(O(2)CR)(6)(py)(3)](ClO(4)) (R = Me
      (1); R = Et (2); R = Ph (3)) has afforded the new tetranuclear mixed-valent
      complexes [Mn(4)O(2)(O(2)CR)(4)L(2)](ClO(4))(2) (R = Me (4); R = Et (5); R = Ph
      (6)) and [Mn(4)O(2)(OMe)(3)(O(2)CR)(2)L(2)(MeOH)](ClO(4))(2) (R = Me (7); R = Et
      (8); R = Ph (9)). Complexes 4-6 were obtained in yields of 20%, 44%, and 37%,
      respectively. They are mixed-valent, with an average Mn oxidation state of +2.5.
      Complexes 7-9 were obtained in yields of 57%, 65%, and 70%, respectively. They
      are also mixed-valent, but with an average Mn oxidation state of +2.75. Complexes
      4 x 2THF and 9 x 3MeOH x H(2)O crystallize in the triclinic space group P1 macro
      and contain [Mn(4)(mu(3)-O)(2)](6+) and [Mn(4)(mu(3)-O)(2)(mu-OMe)(2)](5+) cores,
      respectively, the latter being a new structural type in the family of Mn(4)
      complexes. Reactivity studies of 4-9 have shown that 4-6 can be converted into 7
      9, respectively, and vice versa. The magnetic properties of 5 and 9 have been
      studied by dc and ac magnetic susceptibility techniques. Complex 5 displays
      antiferromagnetic coupling between its Mn ions resulting in a spin ground state
      of S = 0. Complex 9 also displays antiferromagnetic coupling, but the resulting
      ground state is S = (7)/(2), as confirmed by fitting magnetization versus field
      data collected for 9 at low temperatures, which gave S = (7)/(2), D = -0.77 cm(
      1), and g = 1.79. Complex 9 exhibits a frequency-dependent out-of-phase ac
      susceptibility peak, indicative of the slow magnetization relaxation that is
      diagnostic of single-molecule magnetism behavior.

PMID- 11978113
TI  - Highly luminescent, visible-emitting lanthanide macrocyclic chelates stable in
      water and derived from the cyclen framework.
AB  - Two new tetraazamacrocyclic ligands are designed with the aim of sensitizing the
      luminescence of Tb(III) and Eu(III) ions in water: L5 [1,4,7,10-tetrakis[N
      (phenacyl)carbamoylmethyl]-1,4,7,10-tetraazacyclododecane] and L6 [1,4,7,10
      tetrakis[N-(4-phenylphenacyl)carbamoylmethyl]-1,4,7,10-tetraazacyclododecane].
      These ligands react with lanthanide trifluoromethanesulfonates to yield stable
      1:1 complexes in water (log K = 12.89 +/- 0.15 for EuL5). X-ray diffraction on
      [Tb(L5)(H(2)O)](CF(3)SO(3))(3) (P1 macro, a = 13.308(3) A, b = 14.338(3) A, c =
      16.130(3) A, alpha = 101.37(3) degrees, beta = 96.16(3) degrees, gamma = 98.60(3)
      degrees ) shows the Tb(III) ion lying on a C(4) axis and being 9-coordinate, with
      one water molecule bound in its inner coordination sphere. The absolute quantum
      yields are determined in aerated water for the complexes formed with ions used in
      fluoroimmunoassays (Ln = Sm, Eu, Tb, and Dy). Large values are found for
      [Tb(H(2)O)(L5)](3+) and [Eu(H(2)O)(L6)](3+), in line with the molecular design of
      the receptors: 23.1% and 24.7%, respectively. The intense luminescence of these
      ions results from efficient intersystem crossing and L --> Ln energy transfer
      processes, as well as from a suitable shielding of the emitting ions from
      radiationless deactivation.

PMID- 11978114
TI  - The lengths of molybdenum to molybdenum quadruple bonds: correlations,
      explanations, and corrections.
AB  - A systematic search of the Cambridge Crystallographic Database has yielded
      structures of 467 molecules containing, or reported to contain, a molybdenum to
      molybdenum quadruple bond, Mo[quadruple bond]Mo. We have arranged these data as a
      histogram, in order to determine the "normal" range of Mo[quadruple bond]Mo
      lengths, 2.06-2.17 A, as well as to examine molecules in which the Mo[quadruple
      bond]Mo length deviates from the norm. We discuss 24 molecules with exceptionally
      long Mo[quadruple bond]Mo lengths. Another molecule, Mo(2)(pyNC(O)CH(3))(4), was
      previously reported to have an unusually short Mo[quadruple bond]Mo bond.
      However, the structure is highly disordered (probably twinned); thus we have
      prepared and determined the structure of an analogous molecule,
      Mo(2)(pyNC(O)CH(2)CH(3))(4), which displays a completely normal Mo[quadruple
      bond]Mo bond length of over 2.08 A.

PMID- 11978115
TI  - Dinuclear ruthenium(II) polypyridyl complexes containing large, redox-active,
      aromatic bridging ligands: synthesis, characterization, and intramolecular
      quenching of MLCT excited states.
AB  - Two new ruthenium(II) polypyridyl dimers containing the large planar aromatic
      bridging ligands 9,11,20,22-tetraazatetrapyrido[3,2-a:2'3'-c:3' ',2''-l:2''',3'''
      n]pentacene (tatpp) and 9,11,20,22-tetraazatetrapyrido[3,2-a:2'3'-c:3'',2' '
      l:2''',3'''-n]pentacene-10,21-quinone (tatpq) have been synthesized and
      characterized by (1)H and (13)C NMR, MALDI mass spectrometry, and elemental
      analyses. The electronic properties (UV-vis, redox, photophysical) of these
      dimers are analyzed in the context of orbital calculations (PM3 level) on the
      bridging ligands. A localized orbital model is proposed in which low-lying
      acceptor orbitals on the center portion of the ligands effectively quench the
      Ru(II)-based MLCT emission via a mechanism that can be viewed as intramolecular
      electron transfer to specific subunits of the bridges.

PMID- 11978116
TI  - Reactions of trivacant Wells-Dawson heteropolytungstates. Ionic strength and Jahn
      Teller effects on formation in multi-iron complexes.
AB  - Reaction of alpha-P(2)W(15)O(56)(12-) and Fe(III) in a saturated NaCl solution
      produces a trisubstituted Wells-Dawson structure with three low-valent metals,
      alpha-(Fe(III)Cl)(2)(Fe(III)OH(2))P(2)W(15)O(59)(11-) (1). Dissolution of this
      species into 1 M NaBr (Br(-) is non-coordinating) gives the triaquated species
      alpha-(Fe(III)OH(2))(3)P(2)W(15)O(59)(9-) (2). Ionic strength values of 1 M or
      greater are necessary to avoid decomposition of 1 or 2 to the conventional
      sandwich-type complex, alpha beta beta alpha
      (Fe(III)OH(2))(2)Fe(III)(2)(P(2)W(15)O(56))(2)(12-) (3). If the pH is greater
      than 5, a new triferric sandwich, alpha alpha beta alpha
      (NaOH(2))(Fe(III)OH(2))Fe(III)(2)(P(2)W(15)O(56))(2)(14-) (4), forms rather than
      3. Like the previously reported Wells-Dawson-derived sandwich-type structures
      with three metals in the central unit
      ([TM(II)Fe(III)(2)(P(2)W(15)O(56))(P(2)TM(II)(2)W(13)O(52))],(16-) TM = Cu, Co),
      this complex has a central alpha-junction and a central beta-junction. Thermal
      studies suggest that 4 is more stable than 3 over a wide range of temperatures
      and pH values. The intrinsic Jahn-Teller distortion of d-electron-containing
      metal ions incorporated into the external sites of the central multi-metal unit
      impacts the stoichiometry of their incorporation (with a consequent change in the
      inter-POM-unit connectivity, where POM = polyoxometalate). Reaction of non
      distorting Ni(II) with the diferric lacunary sandwich-type POM alpha alpha alpha
      alpha-(NaOH(2))(2)Fe(III)(2)(P(2)W(15)O(56))(2)(16-) (5) produces alpha beta beta
      alpha-(Ni(II)OH(2))(2)Fe(III)(2)(P(2)W(15)O(56))(2)(14-) (6), a Wells-Dawson
      sandwich-type structure with two Ni(II) and two Fe(III) in the central unit. All
      structures are characterized by (31)P NMR, IR, UV-vis, magnetic susceptibility,
      and X-ray crystallography. Complexes 4 and 6 are highly selective and effective
      catalysts for the H(2)O(2)-based epoxidation of alkenes.

PMID- 11978117
TI  - Structure and magnetism of heptanuclear complexes formed on encapsulation of
      hexacyanoferrate(II) with the Mn(II) and Ni(II) complexes of 1,4-bis(2
      pyridylmethyl)-1,4,7-triazacyclononane.
AB  - The reaction of [Mn(dmptacn)OH(2)](2+) and [Ni(dmptacn)OH(2)](2+) (dmptacn = 1,4
      bis(2-pyridylmethyl)-1,4,7-triazacyclononane) with each cyano ligand on
      ferricyanide results in the assembly of heteropolynuclear cations around the
      cyanometalate core and reduction of Fe(III) to Fe(II). In
      [[Mn(dmptacn)CN](6)Fe][ClO(4)](8) x 5H(2)O (1) and
      [[Ni(dmptacn)CN](6)Fe][ClO(4)](8) x 7H(2)O (2), ferrocyanide is encapsulated by
      either six Mn(II) or Ni(II) dmptacn moieties. These same products are obtained
      when ferrocyanide salts are used in the synthesis instead of ferricyanide. A
      binuclear complex, [[Mn(dmptacn)](2)CN][ClO(4)](3) (3), has also been formed from
      KCN and [Mn(dmptacn)OH(2)](2+). For both Mn(II) and Ni(II), the use of the
      pentadentate dmptacn ligand facilitates the formation of discrete cations in
      preference to networks or polymeric structures. 1 crystallizes in the trigonal
      space group R3 macro (No. 148) with a = 30.073(3) A, c = 13.303(4) A, and Z = 3
      and is composed of heptanuclear [[Mn(dmptacn)CN](6)Fe](8+) cations whose charge
      is balanced by perchlorate counteranions. Weak H-bonding interactions between
      neighboring heptanuclear cations and some perchlorate counterions generate an
      infinite 1D chain of alternating [[Mn(dmptacn)CN](6)Fe](8+) and ClO(4)(-) ions
      running along the c-axis. Complex 3 crystallizes in the orthorhombic space group
      Pbcn (No. 60) with a = 16.225(3) A, b = 16.320(2) A, c = 18.052(3) A, and Z = 8
      and is composed of binuclear [[Mn(dmptacn)](2)CN](3+) cations in which the cyano
      bridged Mn(II) centers are in a distorted trigonal prismatic geometry. Variable
      temperature magnetic susceptibility measurements have revealed the presence of a
      weak ferromagnetic interaction between the paramagnetic Mn(II) centers in 1,
      mediated either by the -NC-Fe-CN- bridging units or by Mn-NH...ClO(4-)...NH-Mn
      intercluster pathways.

PMID- 11978118
TI  - Structure and bonding in the aluminum radical species Al x NH(3), HAlNH(2),
      HAlNH(2) x NH(3), and Al(NH(2))(2) studied by means of matrix IR spectroscopy and
      quantum chemical calculations.
AB  - Experimental matrix IR spectra in alliance with extensive quantum chemical
      calculations provide a framework for the detailed evaluation of the structures
      and electronic properties of the doublet species Al x NH(3), Al(NH(3))(2),
      HAlNH(2), HAlNH(2) x NH(3), and Al(NH(2))(2). These species were the products of
      the reaction of Al atoms with NH(3) in an Ar matrix. While the two species Al x
      NH(3) and HAlNH(2) were already sighted in previous experiments, the results
      described herein lead to the first identification and characterization of
      HAlNH(2) x NH(3) and Al(NH(2))(2), the products of the reaction of Al atoms with
      two NH(3) molecules. The results allow a detailed reaction scheme leading to all
      the product species to be established. The unpaired electron in each of the
      species Al x NH(3), Al(NH(3))(2), HAlNH(2), HAlNH(2) x NH(3), and Al(NH(2))(2) is
      located near the Al atom, but there is a significant degree of delocalization,
      especially in Al(NH(2))(2), due to pi bonding interactions. The consequences for
      the barrier to pyramidalization at the N-atom are discussed.

PMID- 11978119
TI  - Charge transfer of iron(III) monomeric and oligomeric aqua hydroxo complexes:
      semiempirical investigation into photoactivity.
AB  - Aqueous hydrolyses of iron(III) solutions were studied using electronic
      spectroscopy. Complete spectra from 200 to 800 nm were obtained for the four
      ferric aqua hydroxo complexes: Fe(H(2)O)(6)(3+), Fe(OH)(H(2)O)(5)(2+),
      Fe(OH)(2)(H(2)O)(4)(+), and the dimer Fe(2)(mu-Omicron Eta)(2)(H(2)O)(8)(4+).
      Semiempirical Zindo/s calculations were employed to assign which types of
      electronic transfers are involved so that the photoactivity as regards the
      photoreduction dissociation Fe(III)(aq) Fe(II)(aq) + OH* can be discussed. Fe(3+)
      exhibits two LMCT from non-bonding p orbitals (nLp) located at 190 and 240 nm.
      Fe(OH)(2+) shows two major nLp(OH) --> d transitions at 205 and 295 nm. As
      regards its geometry, computed investigations using an Fe-OH distance of 2.05 A
      better fit than using a shorter distance ( approximately 1.8 A); the same
      conclusion remains constant for all hydroxo complexes. The dihydroxo form's
      spectrum was confronted to its common cis and trans expectable isomers plus an
      unusual pentacoordinate one. Even if the trans isomer is supposed to be the
      lowest Gibbs free energy species in solution, there is some evidence of the
      presence of the cis form; hence, both species must be close in energy. Other
      isolated nLp(OH) --> d transfer wavelengths are 235, 245, and 335 nm. As for the
      dimer, this study provides some clue in favor of the bis(mu-hydroxo))
      description. Both water and hydroxo ligands are involved along the electronic
      transitions toward only d(1) metal-centered orbitals at 220 and 260 nm for H(2)O,
      335 and 470 nm for OH(-), and 205 nm for both. Charge transfers for the hydrogen
      oxide bridge form Fe(2)(mu-Eta(3)Omicron(2))(H(2)O)(8)(5+) were also computed.
      Finally predictions about the two bis(mu-hydroxo) bridge trimer
      Fe(3)(OH)(4)(H(2)O)(10)(5+) enable one to foresee a huge and broad charge
      transfer in the UV region (approximately 240 nm) followed by a multi nLp(OH) -->
      d(1) transfer extending up to approximately 650 nm.

PMID- 11978120
TI  - Structure and photochemistry of nitrocobalt(III) tetraphenylporphyrin with axial
      triphenylphosphine in toluene solutions.
AB  - Thermal and photochemical reactions of nitroaquacobalt(III) tetraphenylporphyrin,
      (NO(2))(H(2)O)Co(III)TPP, have been investigated in toluene solutions containing
      triphenylphosphine, P phi(3). It is found that Pphi(3) thermally abstracts an
      oxygen atom from the NO(2) moiety of (NO(2))(H(2)O)Co(III)TPP with a rate
      constant 0.52 M(-1) s(-1), resulting in the formation of nitrosylcobalt
      porphyrin, (NO)CoTPP. The 355-nm laser photolysis of (NO(2))(H(2)O)Co(III)TPP at
      low concentrations of P phi(3) (<1.0 x 10(-4) M) gives Co(II)TPP and NO(2) as
      intermediates. The recombination reaction of Co(II)TPP and NO(2) initially forms
      the coordinately unsaturated nitritocobalt(III) tetraphenylporphyrin, (ON
      O)Co(III)TPP, which reacts with P phi(3) to yield
      nitro(triphenylphosphine)cobalt(III) tetraphenylporphyrin, (NO(2))(P
      phi(3))Co(III)TPP. Subsequently, the substitution reaction of the axial P phi(3)
      with H(2)O leads to the regeneration of (NO(2))(H(2)O)Co(III)TPP. From the
      kinetic studies, the substitution reaction is concluded to occur via a
      coordinately unsaturated nitrocobalt(III) porphyrin, (NO(2))Co(III)TPP. At higher
      concentrations of P phi(3) (>4 x 10(-3) M), (NO(2))(H(2)O)Co(III)TPP reacts with
      P phi(3) to form (NO(2))(P phi(3))Co(III)TPP: the equilibrium constant is
      obtained as K = 4.3. The X-ray structure analysis of (NO(2))(P phi(3))Co(III)TPP
      reveals that the P-Co-NO(2) bond angle is 175.0(2) degrees and the bond length Co
      NO(2) is 2.000(7) A. In toluene solutions of (NO(2))(H(2)O)Co(III)TPP containing
      P phi(3) (>4 x 10(-3) M), the major light-absorbing species is (NO(2))(P
      phi(3))Co(III)TPP, which yields (NO)CoTPP by continuous photolysis. The laser
      photolysis of (NO(2))(P phi(3))Co(III)TPP gives Co(II)TPP, NO(2), and P phi(3) as
      initial products. The NO(2) molecule is suggested to be reduced by P phi(3) to
      yield NO, and the reaction between NO and Co(II)TPP gives (NO)CoTPP. The quantum
      yield for the photodecomposition of (NO(2))(P phi(3))Co(III)TPP is determined as
      0.56.

PMID- 11978121
TI  - Reactions of hydroxymesitylboranes with metal alkyls: an approach to new
      sterically hindered (metaloxy)mesitylboranes.
AB  - Reactions of mesitylboronic acid with alkyl derivatives of aluminum R(3)Al (R =
      Me, Et, Bu(i)), gallium (Me(3)Ga), and zinc (Et(2)Zn) were investigated. The
      treatment of mesitylboronic acid, MesB(OH)(2), with trimethylgallium afforded the
      discrete dimer [mu-(MesB(OH)O)GaMe(2)](2) (1), which is the simple example of a O
      metalated boronic acid with no hydrogen bonding in the crystal lattice. In
      addition, the reaction of dimesitylborinic acid, Mes(2)BOH, with diethylzinc
      produced the low-valent zinc compound [(mu-Mes(2)BO)ZnEt](2) (2), which was also
      characterized by X-ray diffraction.

PMID- 11978123
TI  - Electronic structure of diamagnetic and paramagnetic hexanuclear chalcohalide
      clusters of rhenium.
AB  - Hexanuclear chalcohalide clusters of rhenium(III) of general formula
      [Re(6)S(4+x)Cl(10-x)](x-) with x = 1-4 have been studied using quantum chemical
      DFT calculations. The optimized structures reproduce the geometrical features
      found from X-ray data for the members of the series. The relative stability of
      different stereoisomers for the mono- and dianions has been estimated. The
      analysis of the tetraanion series [Re(6)Q(8)X(6)](4-) with Q = S, Se and X = Cl,
      Br, I, and CN demonstrates the influence of the mu(1)- and mu( 3)-ligands on the
      strength of Re-apical ligand bond. It is shown that the tetragonal distortion
      found for the stable oxidized paramagnetic species [Re(6)S(8)Cl(6)]*(3-) results
      from the Jahn-Teller effect for a doubly degenerate electronic state.

PMID- 11978122
TI  - Sterically demanding multidentate ligand tris[(2-(6-methylpyridyl))methyl]amine
      slows exchange and enhances solution state ligand proton NMR coupling to
      (199)Hg(II).
AB  - The solution state coordination chemistry of Hg(ClO(4))(2) with tris[(2-(6
      methylpyridyl))methyl]amine (TLA) was investigated in acetonitrile-d(3) by proton
      NMR. Although Hg(II) is a d(10) metal ion commonly associated with notoriously
      rapid exchange between coordination environments, as many as six ligand
      environments were observed to be in slow exchange on the chemical shift time
      scale at select metal-to-ligand ratios. One of these ligand environments was
      associated with extensive heteronuclear coupling between protons and (199)Hg and
      was assigned to the complex [Hg(TLA)](2+). The (5)J((1)H(199)Hg) = 8 Hz
      associated with this complex is the first example of five-bond coupling in a
      nitrogen coordination compound of Hg(II). The spectral complexity of related
      studies conducted in acetone-d(6) precluded analysis of coordination equilibria.
      Crystallographic characterization of the T-shaped complex
      [Hg(TLAH)(CH(2)COCH(3))](ClO(4))(2) (1) in which two pyridyl rings are pendant
      suggested that the acidity of acetone combined with the poor coordinating
      abilities of the neutral solvent adds additional complexity to solution
      equilibria. The complex crystallizes in the triclinic space group P1 macro with a
      = 9.352(2) A, b = 12.956(2) A, c = 14.199(2) A, alpha = 115.458(10) degrees, beta
      = 90.286(11) degrees, gamma = 108.445(11) degrees, and Z = 2. The Hg-N(amine), Hg
      N(pyridyl), and Hg-C bond lengths in the complex are 2.614(4), 2.159(4), and
      2.080(6) A, respectively. Relevance to development of (199)Hg NMR as a
      metallobioprobe is discussed.

PMID- 11978124
TI  - One- and two-dimensional silver-coordination networks containing pi-sandwiched
      silver-silver interactions.
AB  - The self-assembly of coordination networks from reaction of 2,4,6-trimesityl
      1,3,5-triazine and silver(I) trifluoroacetate is described. A one-dimensional
      linear polymer is formed from solutions deficient in silver while a two
      dimensional, graphite-like sheet is formed from solutions containing 3 equiv of
      silver per triazine. The structurally similar networks both contain triazine
      rings separated by two trifluoroacetate-bridged silver atoms. The two silver
      atoms are effectively sandwiched between two mesityl rings with intermediate
      arene-silver interactions. The silver-silver bond lengths are 2.9731(4) and
      2.9246(5) A in the one-dimensional network and 2.8842(4) A in the two-dimensional
      network.

PMID- 11978125
TI  - Electrochemical and spectral studies of the reactions of aquocobalamin with
      nitric oxide and nitrite ion.
AB  - Electrochemistry and Raman spectroscopy have shown that aquocob(III)alamin
      (Cbl(III)) can be reduced by nitric oxide (NO) to form Cbl(II) on an electrode
      surface. The Cbl(II) formed in this way can bind NO to form nitrosyl-cobalamin,
      Cbl(II)-NO, which is reduced to form Cbl(I) at about -1.0 V vs a KCl saturated
      Ag/AgCl reference electrode. In addition, nitrite was found to bind both Cbl(III)
      and Cbl(II) and a binding constant of 3.5 x 10(2) M(-1) was measured for (NO(2)
      Cbl(II))(1-). UV-vis spectrophotometry and mass spectroscopy were used to show
      that Cbl(I) reduces NO to form Cbl(II)-NO and N(2)O and N(2), and this reaction
      is involved in the cyclic voltammetry of cobalamin in the presence of excess NO
      where a catalytic reduction of NO occurs involving the cycling of Cbl(II)
      NO/Cbl(I). This redox couple is also involved in the electrochemical catalytic
      reduction of nitrite. These results can be used to explain a number of
      physiological effects involving NO interaction in biological systems with added
      cobalamin or with cobalamin in the methionine synthase enzyme.

PMID- 11978126
TI  - Solution and solid state studies of a triangle-square equilibrium: anion-induced
      selective crystallization in supramolecular self-assembly.
AB  - We report that an equilibrium mixture of triangular and square supramolecular
      species results when the flexible, ditopic donor unit, trans-bis(4
      pyridyl)ethylene, is reacted with the ditopic acceptor unit, cis
      (Me(3)P)(2)Pt(OTf)(2), in a one-to-one ratio. Both products are characterized in
      solution, by way of multinuclear NMR, and in the solid state, via X-ray
      crystallography. The effects of water and anions, cobalticarborane versus
      triflate, on the equilibrium are probed. The selective crystallization of either
      of the two species can be accomplished via the appropriate choice of solvents and
      ratio of anions present in the system. The dominant species in solution is not
      always consistent with the most prevalent species in the solid state.

PMID- 11978127
TI  - Tripodal pseudopeptides with three histidine or cysteine donors: synthesis and
      zinc complexation.
AB  - Peptide coupling of benzene-1,3,5-carboxylic acid with 3 equiv of histidine ethyl
      ester or cysteine ethyl ester has yielded the tripodal pseudopeptide ligands THB
      and H(3)TCB. Likewise, the combination of tris(carboxyethyl)nitromethane with 3
      equiv of cysteine ethyl ester gave the tripod H(3)TCM. With zinc salts, the
      pseudopeptides form the insoluble compounds (THB)(2)Zn(5)Cl(10), Zn(3)(TCB)(2),
      and Zn(3)(TCM)(2) which are likely to be coordination polymers. Solution studies
      of THB with potentiometric methods have identified the complex species
      [(THB)(2)Zn](2+), [(THB)Zn-OH(2)](2+), and [(THB)Zn-OH](+). The pK(a) of the zinc
      bound water molecule is 6.2, making the (THB)Zn complex a viable model of
      carbonic anhydrase.

PMID- 11978128
TI  - Mechanistic information on the reversible binding of NO to selected iron(II)
      chelates from activation parameters.
AB  - Mechanistic insight on the reversible binding of NO to Fe(II) chelate complexes
      as potential catalysts for the removal of NO from effluent gas streams has been
      obtained from the temperature and pressure parameters for the "on" and "off"
      reactions determined using a combination of flash photolysis and stopped-flow
      techniques. These parameters are correlated with those for water exchange
      reactions on the corresponding Fe(II) and Fe(III) chelate complexes, from which
      mechanistic conclusions are drawn. Small and positive Delta V(++) values are
      found for NO binding to and release from all the selected complexes, consistent
      with a dissociative interchange (I(d)) mechanism. The only exception in the
      series of studied complexes is the binding of NO to [Fe(II)(nta)(H(2)O)(2)](-).
      The negative volume of activation observed for this reaction supports the
      operation of an I(a) ligand substitution mechanism. The apparent mechanistic
      differences can be accounted for in terms of the electronic and structural
      features of the studied complexes. The results indicate that the aminocarboxylate
      chelates affect the rate and overall equilibrium constants, as well as the nature
      of the substitution mechanism by which NO coordinates to the selected complexes.
      There is, however, no simple correlation between the rate and activation
      parameters and the selected donor groups or overall charge on the iron(II)
      complexes.

PMID- 11978129
TI  - Hydrolysis of tin(II) neo-pentoxide: syntheses, characterization, and X-ray
      structures of [Sn(ONep)(2)](infinity), Sn(5)(mu(3)-O)(2)(mu-ONep)(6), and
      Sn(6)(mu(3)-O)(4)(mu-ONep)(4) where ONep = OCH(2)CMe(3).
AB  - The reaction of [Sn(NMe(2))(2)](2) (1) with 4 equiv of HOCH(2)CMe(3) (HONep)
      leads to the isolation of [Sn(ONep)(2)](infinity) (2). Each Sn atom is four
      coordinated with mu-ONep ligands bridging the metal centers; however, if the free
      electrons of the Sn(II) metal center are considered, each Sn center adopts a
      distorted trigonal bipyramidal (TBP) geometry. Through (119)Sn NMR experiments,
      the polymeric compound 2 was found to be disrupted into smaller oligomers in
      solution. Titration of 2 with H(2)O led to the identification of two unique
      hydrolysis products characterized by single-crystal X-ray diffraction as
      Sn(5)(mu(3)-O)(2)(mu-ONep)(6) (3) and Sn(6)(mu(3)-O)(4)(mu-ONep)(4) (4). Compound
      3 consists of an asymmetrical molecule that has five Sn atoms arranged in a
      square-based pyramidal geometry linked by four basal mu-ONep ligands, two facial
      mu(3)-O, and two facial mu-ONep ligands. Compound 4 was solved in a novel
      octahedral arrangement of six Sn cations with an asymmetric arrangement of mu(3)
      O and mu-ONep ligands that yields two square base pyramidal and four pyramidal
      coordinated Sn cations. These compounds were further identified by multinuclear
      ((1)H, (13)C, (17)O, and (119)Sn) solid-state MAS and high resolution, solution
      NMR experiments. Because of the complexity of the compounds and the accessibility
      of the various nuclei, 2D NMR experiments were also undertaken to elucidate the
      solution behavior of these compounds. On the basis of these studies, it was
      determined that while the central core of the solid-state structures of 3 and 4
      is retained, dynamic ligand exchange leads to more symmetrical molecules in
      solution. Novel products 3 and 4 lend structural insight into the stepwise
      hydrolysis of Sn(II) alkoxides.

PMID- 11978130
TI  - Synthesis and characterization of dimetallic oxorhenium(V) and dioxorhenium(VII)
      compounds, and a study of stoichiometric and catalytic reactions.
AB  - Chelating dithiolate ligands--e.g., mtp from 2-(mercaptomethyl)thiophenol, edt
      from 1,2-ethanedithiol, and pdt from 1,3-propanedithiol--stabilize high-valent
      oxorhenium(V) against hydrolytic and oxidative decomposition. In addition to the
      dithiolate chelating to a single rhenium, one sulfur forms a coordinate bond to
      the other rhenium. In one arrangement this gives a dimer with a nearly planar
      diamond core with different internal Re-S distances. The new compounds are
      [MeReO(edt)](2) (2) and [MeReO(pdt)](2) (3), which can be compared to the
      previously known [MeReO(mtp)](2) (1). Another mode of synthesis leads to
      [ReO](2)(mtp)(3) (5) and [ReO](2)(edt)(3) (6). They, too, have similar Re(2)S(2)
      cores that involve donor atoms from two of the dithiolate ligands; the third
      dithiolate chelates one of the rhenium atoms. Gentle hydrolysis of 1 affords
      [Bu(n)4][[MeReO(mtp)](2)(mu-OH)] (7) in low yield. It appears to be the first
      example of this structural type for rhenium. The use of dithioerythritol as a
      starting material allowed the synthesis of a dioxorhenium(VII) compound,
      [MeReO(2)](2)(dte) (8). Its importance lies in understanding the role such
      compounds are believed to play as intermediates in oxygen atom catalysis.
      Ligation of the dimers 1-3 converts them into monomeric compounds,
      MeReO(dithiolate)L. These reactions go essentially to completion for L = PPh(3),
      but reach an equilibrium for L = NC(5)H(4)R. With R = 4-Ph, the values of K/10(3)
      L mol(-1) for the reactions (1-3) + 2L = 2MeReO(dithiolate)L are identical within
      3 sigma: 1.15(3) (1), 1.24(4) (2), and 1.03(16) (3). The rates of monomer
      formation follow the rate law -d ln [dimer]/dt = k(a)[L] + k(b)[L](2). These
      trends were found: (1) phosphines are slow to react compared to pyridines, (2)
      the edt dimer 2 reacts much more rapidly than 1 and 3. Dimer 1 and
      MeReO(mtp)PPh(3) both catalyze oxygen atom transfer: PicO + PPh(3) --> Pic +
      Ph(3)PO. Compound 1 is ca. 90 times more reactive, which can be attributed to its
      lability toward small ligands as opposed to the low rate of displacement of
      PPh(3) from the mononuclear catalyst. The kinetics of this reaction follows the
      rate law -d[PicO]/dt = k[PicO][1]/[1 + kappa[PPh(3)]], with k = 5.8 x 10(6) L
      mol(-1) s(-1) and kappa = 3.5 x 10(2) L mol(-1) at 23 degrees C in benzene. A
      mechanism has been proposed to account for these findings.

PMID- 11978131
TI  - [Cd(II)(bpdc).H(2)O](n): a robust, thermally stable porous framework through a
      combination of a 2-D grid and a cadmium dicarboxylate cluster chain (H(2)bpdc =
      2,2'-Bipyridyl-4,4'-dicarboxylic acid).
AB  - The synthesis and characterization of a cadmium(II) coordination polymer,
      [Cd(C(12)H(6)N(2)O(4)) x H(2)O](n)() (1), is reported. A single-crystal X-ray
      analysis shows that compound 1 presents a non-interpenetrating three-dimensional
      porous host containing one-dimensional hydrophilic channels, where guest water
      molecules reside. The strategy in designing the 3-D framework architecture is
      based on a combination of two building subunits: a porous two-dimensional grid of
      (4,4) topology and a metal dicarboxylate cluster chain. Both subunits are
      assembled from the coordination of a cadmium ion with a three-connecting organic
      modular ligand, 2,2'-bipyridyl-4,4'-dicarboxylic acid (H(2)bpdc). The results of
      thermogravimetric analysis and powder X-ray diffraction study show that the
      framework rigidity of compound 1 remains intact upon the removal of guest
      molecules, and maintains the thermal stability up to 440 degrees C. The second
      row transition-metal ions are capable of engaging higher coordination modes
      (e.g., hepta- and octacoordination) because of their atomic sizes and intrinsic
      electron configurations. Our results show that the heptacoordinated cadmium
      center plays an important role in the overall framework rigidity and high thermal
      stability of compound 1. Crystal data for 1: Cd(C(12)H(6)N(2)O(4)) x H(2)O,
      triclinic, space group P1 macro, a = 6.7843(5) A, b = 9.3299(7) A, c = 9.4439(7)
      A, alpha = 104.629(1) degrees, beta = 92.324(1) degrees, gamma = 100.416(1)
      degrees, Z = 2.

PMID- 11978132
TI  - Mixed-metal supramolecular complexes coupling phosphine-containing Ru(II) light
      absorbers to a reactive Pt(II) through polyazine bridging ligands.
AB  - Supramolecular bimetallic Ru(II)/Pt(II) complexes
      [(tpy)Ru(PEt(2)Ph)(BL)PtCl(2)](2+) and their synthons [(tpy)Ru(L)(BL)](n)()(+)
      (where L = Cl(-), CH(3)CN, or PEt(2)Ph; tpy = 2,2':6',2''-terpyridine; and BL =
      2,2'-bipyrimidine (bpm) or 2,3-bis(2-pyridyl)pyrazine (dpp)) have been
      synthesized and studied by cyclic voltammetry, electronic absorption
      spectroscopy, mass spectral analysis, and (31)P NMR. The mixed-metal bimetallic
      complexes couple phosphine-containing Ru chromophores to a reactive Pt site.
      These complexes show how substitution of the monodentate ligand on the
      [(tpy)RuCl(BL)](+) synthons can tune the properties of these light absorbers (LA)
      and incorporate a (31)P NMR tag by addition of the PEt(2)Ph ligand. The redox
      potentials for the Ru(III/II) couples occur at values greater than 1.00 V versus
      the Ag/AgCl reference electrode and can be tuned to more positive potentials on
      going from Cl(-) to CH(3)CN or PEt(2)Ph (E(1/2) = 1.01, 1.55, and 1.56 V,
      respectively, for BL = bpm). The BL(0/-) couple at -1.03 (bpm) and -1.05 V (dpp)
      for [(tpy)Ru(PEt(2)Ph)(BL)](2+) shifts dramatically to more positive potentials
      upon the addition of the PtCl(2) moiety to -0.34 (bpm) and -0.50 V (dpp) for the
      [(tpy)Ru(PEt(2)Ph)(BL)PtCl(2)](2+) bridged complex. The lowest energy electronic
      absorption for these complexes is assigned as the Ru(d pi) --> BL(pi*) metal-to
      ligand charge transfer (MLCT) transition. These MLCT transitions are tuned to
      higher energy in the monometallic synthons when Cl(-) is replaced by CH(3)CN or
      PEt(2)Ph (516, 452, and 450 nm, for BL = bpm, respectively) and to lower energy
      when Pt(II)Cl(2) is coordinated to the bridging ligand (560 and 506 nm for BL =
      bpm or dpp). This MLCT state displays a broad emission at room temperature for
      all the dpp systems with the [(tpy)Ru(PEt(2)Ph)(dpp)PtCl(2)](2+) system
      exhibiting an emission centered at 750 nm with a lifetime of 56 ns. These
      supramolecular complexes [(tpy)Ru(PEt(2)Ph)(BL)PtCl(2)](2+) represent the
      covalent linkage of TAG-LA-BL-RM assembly (TAG = NMR active tag, RM = Pt(II)
      reactive metal).

PMID- 11978133
TI  - Reaction of silicate minerals to form tetramethoxysilane.
AB  - Several silicon dioxide sources were used as reagents in the base-mediated
      reaction with dimethyl carbonate (DMC) to make tetramethoxysilane (Q'). Several
      commercially available diatomaceous earth materials were investigated. High
      throughput screening was employed to explore over 200 silicate rocks and minerals
      as alternative silicon dioxide sources for formation of Q' from DMC and base.
      Amorphous silicon dioxide materials are effective reagents for the Q' forming
      reaction. Effective silicon dioxide sources in addition to the diatomaceous earth
      materials include opal and various synthetic silicates (Li, Co, and Ca).

PMID- 11978134
TI  - Pyridylazole chelation of oxorhenium(V) and imidorhenium(V). Rates and trends of
      oxygen atom transfer from Re(V)O to tertiary phosphines.
AB  - The concerned azoles are 2-(2-pyridyl)benzoxazole (pbo) and 2-(2
      pyridyl)benzthiazole (pbt). These react with ReOCl(3)(PPh(3))(2) in benzene,
      affording Re(V)OCl(3)(pbo) and Re(V)OCl(3)(pbt), which undergo facile oxygen atom
      transfer to PPh(2)R (R = Ph, Me) in dichloromethane solution, furnishing
      Re(III)(OPPh(2)R)Cl(3)(pbo) and Re(III)(OPPh(2)R)Cl(3)(pbt). The oxo species
      react with aniline in toluene solution, yielding the imido complexes
      Re(V)(NPh)Cl(3)(pbo) and Re(V)(NPh)Cl(3)(pbt). The X-ray structures of pbt,
      ReOCl(3)(pbt), Re(OPPh(3))Cl(3)(pbt), and Re(NPh)Cl(3)(pbo) are reported. The
      lattice of pbt consists of stacked dimers. In all the complexes the azole ligand
      is N,N-chelated and the ReCl(3) moiety is meridionally disposed. In ReOCl(3)(pbt)
      the metal-oxo bond length is 1.607(9) A. The second-order rates and the
      associated activation parameters of the oxygen atom transfer reactions of the
      Re(V)O chelates with PPh(2)R are reported. The large and negative entropy of
      activation (approximately -24 eu) is consistent with an associative pathway
      involving nucleophilic phosphine attack. The rate increases with phosphine
      basicity (PPh(2)Me > PPh(3)) and azole heteroatom electronegativity (O(pbo) >
      S(pbt)). Logarithmic rate constants for ReOCl(3)(pbo), ReOCl(3)(pbt), and
      ReOCl(3)(pal) are found to correlate linearly with Re(VI)O/Re(V)O reduction
      potentials (pal is pyridine-2-(N-p-tolyl)aldimine). The relatively low rate
      constant of ReOCl(3)(pbt) compared to that of ReOCl(3)(pal) is consistent with
      the observed shortness of the metal-oxo bond in the former. Crystal data are as
      follows: (pbt) empirical formula C(12)H(8)N(2)S, crystal system orthorhombic,
      space group Pca2(1), a = 13.762(9) A, b = 12.952(8) A, c = 11.077(4) A, V =
      1974(2) A(3), Z = 8; (ReOCl(3)(pbt)) empirical formula C(12)H(8)Cl(3)N(2)OSRe,
      crystal system monoclinic, space group P2(1)/c, a = 11.174(7) A, b = 16.403(10)
      A, c = 7.751(2) A, beta = 99.35(4) degrees, V = 1401.8(13) A(3), Z = 4;
      (Re(NPh)Cl(3)(pbo)) empirical formula C(18)H(13)Cl(3)N(3)ORe, crystal system
      monoclinic, space group P2(1)/c, a = 9.566(6) A, b = 16.082(8) A, c = 11.841(5)
      A, beta = 94.03(4) degrees, V = 1817(2) A(3), Z = 4.

PMID- 11978136
TI  - Clinical management of pyoderma gangrenosum.
AB  - Pyoderma gangrenosum is a noninfectious neutrophilic dermatosis that usually
      starts with sterile pustules which rapidly progress to painful ulcers of variable
      depth and size with undermined violaceous borders. In 17 to 74% of cases,
      pyoderma gangrenosum is associated with an underlying disease, most commonly
      inflammatory bowel disease, rheumatological or hematological disease or
      malignancy. Diagnosis of pyoderma gangrenosum is based on a history of an
      underlying disease, typical clinical presentation and histopathology, and
      exclusion of other diseases that would lead to a similar appearance. Randomized,
      double-blinded prospective multicenter trials investigating the treatment of
      pyoderma gangrenosum are not available. The treatments with the best clinical
      evidence are systemic corticosteroids (in the initial phase usually 100 to 200
      mg/day) and cyclosporine (mainly as a maintenance treatment). Combinations of
      corticosteroids with cytotoxic drugs such as azathioprine, cyclophosphamide or
      chlorambucil are used in patients with disease that is resistant to
      corticosteroids. The combination of corticosteroids with sulfa drugs, such as
      dapsone, or clofazimine, minocycline and thalidomide, has been used as a
      corticosteroid-sparing alternative. Limited experience has been documented with
      methotrexate, colchicine, nicotine, and mycophenolate mofetil, among other drugs.
      Alternative treatments include local application of granulocyte-macrophage colony
      stimulating factor, intravenous immunoglobulins and plasmapheresis. Skin
      transplants (split-skin grafts or autologous keratinocyte grafts) and the
      application of bioengineered skin is useful in selected cases in conjunction with
      immunosuppression. Topical therapy with modern wound dressings is useful to
      minimize pain and the high risk of secondary infection. The application of
      topical antibacterials cannot be recommended because of their potential to
      sensitize and their questionable efficacy, but systemic antibacterial therapy is
      mandatory when infection is present. Despite recent advances in therapy, the
      prognosis of pyoderma gangrenosum remains unpredictable.

PMID- 11978135
TI  - Topical corticosteroid-induced adrenocortical insufficiency: clinical
      implications.
AB  - Topical corticosteroids are often prescribed for the treatment of dermatological
      disorders. However, systemic adrenal insufficiency may result from their overuse.
      Current literature detailing both laboratory and clinical findings was analyzed,
      in the hopes of evaluating the health-risk potential of topical corticosteroids
      in producing adrenal insufficiency. Risk factors identified in this report
      included use of high potency corticosteroids, occlusive or prolonged treatment
      application, and use in thin-skinned areas. Other patients at risk for
      development of adrenal suppression include infants and those with damaged skin
      barriers. Several diagnostic tests may be utilized to measure adrenal function,
      though each has its limitations. The most common tests include measurement of
      plasma total cortisol, 24-hour steroid, adrenocorticotrophin hormone stimulation
      and insulin tolerance. The report finds strong laboratory evidence of adrenal
      hypofunction. Additionally, clinical reversible adrenal insufficiency has been
      observed on rare occasions. Therefore, topical corticosteroids should be used
      with an increased awareness of the potential for systemic adrenal suppressive
      effects. However, since nonreversible clinical secondary adrenocortical
      insufficiency disease has not been clearly documented with even class I topical
      corticosteroids, native adrenal supplementation in periods of stress appears
      unnecessary; rare exceptions cannot be excluded.

PMID- 11978137
TI  - Novel therapies for psoriasis.
AB  - The T cell-driven immunopathogenesis of psoriasis has been well recognized since
      cyclosporine first revolutionized the treatment of psoriasis 20 years ago. Almost
      all investigative and clinical research subsequently, has concentrated on
      elucidating the specifics of antigen presentation, T cell interaction and the
      production of specific cytokines. The role of the keratinocyte, previously
      thought to be the primary target cell in psoriasis pathogenesis, has been
      relegated to a secondary role and the mechanism of action of systemic
      methotrexate in psoriasis has been challenged, the primary role of the T
      lymphocyte is now well known. While psoriasis has traditionally been treated "ab
      initio" with topical medications (corticosteroids, vitamin D(3), and retinoid
      derivatives), either singly, in combination, or with ultraviolet B (UVB) or
      psoralens and ultraviolet A (PUVA) therapy, the role of systemic medications has
      assumed greater prominence. Thus, three systemic medications currently are
      approved worldwide for the treatment of moderate to severe forms of psoriasis,
      namely cyclosporine, methotrexate and acitretin. The first two are likely to give
      significant clearing (greater than 75%) in the majority of cases, whereas
      acitretin is significantly less effective as monotherapy, but may approach
      methotrexate and cyclosporine in efficacy, if combined with PUVA or UVB
      phototherapy. The main limitations of these three drugs remain organ toxicity,
      especially hepatic toxicity with methotrexate, hypertension and nephrotoxicity
      with cyclosporine, and teratogenicity and mucocutaneous toxicity with acitretin.
      Thus, the need for more specific systemic therapy, targeting the T lymphocyte.
      This has become the major area of clinical research interest over the past 5
      years, with the promise of longer-term disease control (improved remissions) and
      less organ toxicities. Currently, there are over 15 of these "biologic" drugs in
      various stages of development and clinical trials, either by the subcutaneous,
      intramuscular or intravenous route. The three main variables are the rapidity of
      onset, percentages of improvement and remission rates. Without exception, these
      new systemic agents appear to be remarkably free of systemic organ toxicities
      (liver, renal, bone-marrow, etc.), with adverse effects being limited to mild flu
      like symptoms with the anticipated increase in infections (e.g., herpes simplex)
      being either equal to placebo or only marginally increased. Not all these agents
      under evaluation give clinical responses equal to methotrexate or cyclosporine
      (75% or greater clearing in 75% of cases). In addition, response rates may be
      slower with some therapies versus others. However, the need for intermittent
      administration even by the injectable route, longer remissions, lack of systemic
      organ toxicities and the potential for safer usage in females of child-bearing
      age, make a compelling argument for widespread acceptance by both patients and
      the dermatological community. Other modalities under clinical evaluation include
      vitamin D and retinoid drugs, topically and systemically, with effects on nuclear
      receptors, as well as more specific wavelengths (308 to 311 nm) of UVB
      phototherapy with application for more localized forms of psoriasis. For the 2 to
      3% of the worldwide population of patients with psoriasis the future has never
      looked brighter.

PMID- 11978138
TI  - Atopic dermatitis: the role of recombinant interferon-gamma therapy.
AB  - Atopic dermatitis is a common, chronic, relapsing cutaneous disease with typical
      cellular and humoral immunologic abnormalities that can result in significant
      physical and psychological morbidity to the patient. Atopic dermatitis typically
      begins in childhood and can often persist through adolescence into adulthood.
      Although there are a variety of treatments for atopic dermatitis, many patients'
      symptoms do not improve or they have adverse reactions to medications, requiring
      the search for other, effective therapeutic agents. A number of inflammatory and
      immunological abnormalities have long been noted in patients with atopic
      dermatitis. Although great strides have been made in understanding the causes,
      the complex pathophysiology of atopic dermatitis is still not completely
      understood. Most notably, patients with atopic dermatitis often have an elevation
      of serum immunoglobulin (Ig) E levels, depressed cellular immunity, elevated
      blood eosinophilia, and increased interleukin (IL)-4 production. In addition,
      peripheral blood mononuclear cells of patients with atopic dermatitis produce
      reduced levels of interferon-gamma spontaneously and in response to stimuli. Due
      to this constellation of features, atopic dermatitis was initially viewed as a
      prototypical type 2 helper T lymphocyte (T(h2)) disease. These immunological
      findings led to a number of clinical trials with recombinant interferon-gamma in
      patients who had severe, unremitting atopic dermatitis. Treatment with
      recombinant interferon-gamma was postulated to be able to correct the
      immunological imbalances in patients with atopic dermatitis by decreasing serum
      IgE levels, IL-4 levels, restoring immune balance, and thereby leading to
      clinical improvement. Initial open-label studies, a double-blind placebo trial,
      and long-term open-label studies have demonstrated the clinical efficacy and
      tolerability of recombinant interferon-gamma in a subset of patients with severe,
      unremitting atopic dermatitis. Patients receiving treatment often had marked
      decreases in severity of clinical parameters: erythema, edema/indurations,
      pruritus, excoriations, dryness, lichenification and associated reduction in
      total body surface area involvement. Surprisingly, treatment with recombinant
      interferon-gamma did not lower serum IgE levels refuting the hypothesized
      mechanism by which interferon-gamma would bring about clinical improvement in
      patients with atopic dermatitis. Instead, decreases were noted in absolute white
      blood cell and eosinophil counts that tended to correlate with clinical
      improvement. Although the exact mechanism by which recombinant interferon-gamma
      brings about clinical changes in patients with atopic dermatitis is unknown,
      recombinant interferon-gamma should be considered a possible therapy for patients
      with atopic dermatitis.

PMID- 11978139
TI  - Sunscreens: safety, efficacy and appropriate use.
AB  - Promoting sunscreen use is an integral part of prevention programmes aimed at
      reducing ultraviolet (UV) radiation-induced skin damage and skin cancers.
      Protection against both UVB and UVA radiation is advocated. Most sunscreens
      combine chemical UV absorbing sunscreens and physical inorganic sunscreens, which
      reflect UV, to provide broad-spectrum protection. Newer triazole and camphor
      derivative based sunscreens, also provide broad-spectrum protection and are more
      cosmetically acceptable than many traditional agents. Currently licensed
      sunscreen ingredients in common use rarely cause allergic or photoallergic
      reactions. Vitamin D levels are not significantly affected by regular use of a
      sunscreen. Sunscreen use reduces both the development of precancerous solar
      keratosis and the recurrence of squamous cell carcinomas. Sunscreen use early in
      life may be important in prevention of basal cell carcinomas. Increased melanoma
      risk is influenced by the behaviour patterns of regular sunscreen users, as
      opposed to any direct effect of sunscreens. Sun protection factor (SPF) is
      affected by application density, water resistance and other factors. An adequate
      SPF for an individual should be balanced to skin phenotype and exposure habits.
      The correct use of sunscreens should be combined with the avoidance of midday sun
      and the wearing of protective clothing and glasses, as part of an overall sun
      protection regimen.

PMID- 11978140
TI  - Treatment of cutaneous T cell lymphoma: current status and future directions.
AB  - The treatment of cutaneous T cell lymphoma (CTCL), which includes mycosis
      fungoides and Sezary syndrome, has been in a state of continual change over
      recent decades, as new therapies are constantly emerging in the search for more
      effective treatments for the disease. However, prognosis and survival of patients
      with CTCL remains dependent upon overall clinical stage (stage IA-IVB) at
      presentation, as well as response to therapy. Past therapies have been limited by
      toxicity or the lack of consistently durable responses, and few treatments have
      been shown to actually alter survival, especially in the late stages of disease.
      Even aggressive chemotherapy has not been shown to improve overall survival
      compared to conservative sequential therapy in advanced disease, and adds the
      risk of immunosuppressive complications. Over the last decade, extracorporeal
      photopheresis has been the only single treatment that has been shown to improve
      survival in patients with Sezary syndrome, although its true efficacy and place
      in combination therapy remain unclear. Much of the focus of current research has
      been on combinations of skin-directed therapies and biological response
      modifiers, which improve response rates. The results of various trials over the
      years have also brought into favor the use of post-remission maintenance therapy
      with topical corticosteroids, topical mechlorethamine (nitrogen mustard),
      interferon-alpha, or phototherapy to prevent disease relapse. Recent novel
      developments in CTCL therapy include oral bexarotene, a retinoid X receptor
      selective retinoid that has activity in all stages of CTCL, and the topical gel
      formulation of bexarotene, which plays a role in treating localized lesions. US
      Food and Drug Administration (FDA)-approved, oral systemic bexarotene has the
      advantage of a 48% overall response rate at a dosage of 300 mg/m(2)/day, and
      avoids immunosuppression and risk of central line and catheter-related infectious
      complications that are associated with other systemic therapies. Monitoring of
      triglycerides and use of concomitant lipid-lowering agents and thyroid
      replacement is required in most patients. Also recently FDA-approved, denileukin
      diftitox is the first of a novel class of fusion toxin proteins and is selective
      for interleukin-2R (CD25+) T cells, targeting the malignant T cell clones in
      CTCL. Denileukin diftitox is associated with capillary leak syndrome in 20 to 30%
      of patients, which may be ameliorated by hydration and corticosteroids. Higher
      response rates are possible by combining bexarotene with "statin" drugs and
      active CTCL therapies. Studies are being conducted on combining bexarotene and
      denileukin diftitox with other modalities. Biological response modifier therapies
      that are in current or future investigational trials include topical tazarotene,
      pegylated interferon, interleukin-2, and interleukin-12. At the forefront of
      systemic chemotherapy development, pegylated liposomal doxorubicin, gemcitabine,
      and pentostatin appear to have the greatest potential for success in CTCL
      therapy. Bone marrow transplantation, which is currently limited by the risk of
      graft-versus-host disease, offers the greatest potential for disease cure.
      Further developments for CTCL may include more selective immunomodulatory agents,
      vaccines, and monoclonal antibodies.

PMID- 11978141
TI  - Clinical evaluation of 40% urea and 12% ammonium lactate in the treatment of
      xerosis.
AB  - BACKGROUND: Urea and ammonium lactate are used for the treatment of xerosis, with
      different degrees of success. This study compares the clinical effectiveness of
      these two agents. OBJECTIVE: To compare the effectiveness and tolerance of a 40%
      urea topical cream (Carmol 40) from Doak Dermatologics, a subsidiary of Bradley
      Pharmaceuticals, Inc., and 12% ammonium lactate topical lotion (Lac-Hydrin 12%)
      from Westwood Squibb, a division of Bristol-Myers Squibb. METHODS: A randomized,
      double-blind, bilateral paired comparison study was conducted involving 25 men
      and women who were undergoing treatment for moderate to severe xerosis. The study
      included evaluations upon initiation of the study, after a 14-day treatment
      period and treatment follow-up on day 28. RESULTS: Eighteen study participants
      completed the entire 28-day evaluation period. Evaluation of treatment benefit
      was based on instrumental measurement of water loss from the skin surface, skin
      capacitance, skin desquamation, skin roughness, subject self assessment of skin
      and investigator evaluation. Results indicated that clinical observation ratings
      by patients and investigators, as well as instrument measures, show differences
      between the two treatments. Most measures show that improvement is achieved in
      less time with 40% urea cream than with 12% ammonium lactate lotion. On day 14,
      the 40% urea cream was superior to the 12% ammonium lactate lotion as measured by
      skin roughness, fissure reduction, thickness and dryness. DISCUSSION: At day 14
      of treatment, 40% urea cream was superior to 12% ammonium lactate for most of the
      instrumental and clinical assessments.

PMID- 11978142
TI  - Cutaneous drug reaction case reports: from the world literature.

PMID- 11978144
TI  - Fomivirsen: clinical pharmacology and potential drug interactions.
AB  - Fomivirsen sodium is a 21-base phosphorothioate oligodeoxynucleotide
      complementary to the messenger RNA of the major immediate-early region proteins
      of human cytomegalovirus, and is a potent and selective antiviral agent for
      cytomegalovirus retinitis. Following intravitreal administration, fomivirsen is
      slowly cleared from vitreous with a half-life of approximately 55 hours in
      humans. Preclinical studies show that fomivirsen distributes to retina and is
      slowly metabolised by exonuclease digestion. Clearance from retina was shown to
      be similarly slow following loading from the vitreous. The estimated half-life
      for clearance of fomivirsen from retina was 78 hours in monkeys following a 115
      microg dose. Because of the low doses coupled with slow disposition from the eye,
      measurable concentrations of drug are not detected in the systemic circulation
      following intravitreal administration. Systemically administered phosphorothioate
      oligodeoxynucleotides are highly bound to albumin and alpha2-macroglobulin in
      blood plasma. Because fomivirsen does not compete for oxidative metabolic
      processes involved in clearance of many xenobiotics, the most likely mechanism
      for drug interactions may be altered protein binding of a coadministered drug.
      The extremely low systemic exposure to this oligodeoxynucleotide following
      intravitreal administration largely negates its potential ability to interact
      with systemically administered drugs. Even if fomivirsen were able to access the
      blood, protein binding assays indicate that drugs that are site I and site II
      binders of albumin (warfarin, ibuprofen, salicylic acid) are not displaced in the
      presence of phosphorothioate oligodeoxynucleotides of various sequences at
      concentrations orders of magnitude higher than that seen for fomivirsen.
      Administration of fomivirsen with numerous systemically administered
      antiretrovirals (for example zidovudine and zalcitabine) as well as systemically
      administered anticytomegalovirus agents such as foscarnet and ganciclovir has
      been reported to be well tolerated. The only reported warning is a recommendation
      against administration within 2 to 4 weeks of cidofovir treatment due to an
      increased risk of ocular inflammation.

PMID- 11978143
TI  - The mucosa of the small intestine: how clinically relevant as an organ of drug
      metabolism?
AB  - The intestinal mucosa is capable of metabolising drugs via phase I and II
      reactions. Increasingly, as a result of in vitro and in vivo (animal and human)
      data, the intestinal mucosa is being implicated as a major metabolic organ for
      some drugs. This has been supported by clinical studies of orally administered
      drugs (well-known examples include cyclosporin, midazolam, nifedipine and
      tacrolimus) where intestinal drug metabolism has significantly reduced oral
      bioavailability. This review discusses the intestinal properties and processes
      that contribute to drug metabolism. An understanding of the interplay between the
      processes controlling absorption, metabolism and P-glycoprotein-mediated efflux
      from the intestinal mucosa into the intestinal lumen facilitates determination of
      the extent of the intestinal contribution to first-pass metabolism. The clinical
      relevance of intestinal metabolism, however, depends on the relative importance
      of the metabolic pathway involved, the therapeutic index of the drug and the
      inherent inter- and intra-individual variability. This variability can stem from
      genetic (metabolising enzyme polymorphisms) and/or non-genetic (including
      concomitant drug and food intake, route of administration) sources. An
      overwhelming proportion of clinically relevant drug interactions where the
      intestine has been implicated as a major contributor to first-pass metabolism
      involve drugs that undergo cytochrome P450 (CYP) 3A4-mediated biotransformation
      and are substrates for the efflux transporter P-glycoprotein. Much work is yet to
      be done in characterising the clinical impact of other enzyme systems on drug
      therapy. In order to achieve this, the first-pass contributions of the intestine
      and liver must be successfully decoupled.

PMID- 11978146
TI  - Grapefruit juice reduces the oral bioavailability of fexofenadine but not
      desloratadine.
AB  - BACKGROUND: Certain foods, such as grapefruit juice, are known to substantially
      alter the bioavailability of some drugs. These effects may be mediated by
      interactions with enzyme systems, such as cytochrome P450, or with active
      transporter systems, such as P-glycoprotein and organic anion transporting
      polypeptides. OBJECTIVE: To assess the effect of consumption of grapefruit juice
      on the oral bioavailability of two nonsedating antihistamines, fexofenadine and
      desloratadine. DESIGN: Non-blinded, randomised, single-dose, four-way crossover
      study. PARTICIPANTS: Twenty-four healthy adult volunteers. INTERVENTIONS: Single
      oral doses of desloratadine 5mg and fexofenadine 60mg taken without and with
      grapefruit juice (pretreatment with 240ml of double-strength juice three times
      daily for 2 days prior to administration of study drug, plus the same amount
      simultaneously with, and 2 hours after, the drug dose). Each treatment was
      separated by at least 10 days. MAIN OUTCOME MEASURES: Log-transformed
      pharmacokinetic parameters [peak plasma concentration (C(max)) and area under the
      curve (AUC)], time to maximum concentration, elimination half-life and
      electrocardiographic (ECG) parameters. RESULTS: Comparing the ratio of the
      pharmacokinetic parameter means (C(max) and AUC) with and without grapefruit
      juice (expressed as a percentage), the rate (C(max)) and extent (AUC) of
      absorption of fexofenadine were reduced by 30% by consumption of grapefruit
      juice. In contrast, the bioavailability of desloratadine was unaffected by
      grapefruit juice. No clinically significant changes in ECG parameters were
      observed following coadministration of grapefruit juice with desloratadine or
      fexofenadine compared with either antihistamine given alone. CONCLUSION: The
      bioavailability of drugs that do not undergo significant intestinal or hepatic
      metabolism, such as fexofenadine, may be altered when administered with agents
      that influence drug transport mechanisms.

PMID- 11978147
TI  - Lipid-lowering drug use and cardiovascular events after myocardial infarction.
AB  - BACKGROUND: The benefits of lipid-lowering drug treatment for the secondary
      prevention of coronary heart disease have been well established by randomized,
      controlled trials. Nonetheless, the risk of events has not been compared directly
      for inhibitors of hydroxymethylglutaryl coenzyme A reductase (statins) and non
      statin lipid-lowering drugs. Further, it remains uncertain whether patients in
      usual practice who are treated with lipid-lowering drugs after myocardial
      infarction (MI) gain a similar benefit with regard to the risk of cardiovascular
      events compared with patients in randomized, controlled trials. OBJECTIVE: To
      assess the association between lipid-lowering drug therapies in usual clinical
      practice and the risk of cardiovascular events in patients with a first MI who
      were discharged alive from the hospital. METHODS: An inception-cohort study was
      performed among 1956 enrollees of Group Health Cooperative who sustained an
      incident MI between July 1986 and December 1996 and survived for at least 6
      months after hospitalization. Subjects with untreated low-density-lipoprotein
      cholesterol concentrations > 130 mg/dL or untreated total cholesterol
      concentrations >200 mg/dL were included. The median duration of follow-up after
      the first MI was 3.3 years. Medical record review was used to collect information
      on cardiovascular risk factors. Computerized pharmacy records were used to assess
      antihyperlipidemic drug use during the first 6 months after hospitalization.
      RESULTS: Compared with 1263 subjects who did not receive lipid-lowering drug
      treatment, 373 subjects who received statins had a lower risk of recurrent
      coronary events (relative risk [RR] 0.59; 95% CI 0.39 to 0.89), stroke (RR 0.82;
      95% CI 0.35 to 1.95), atherosclerotic cardiovascular mortality (RR 0.49; 95% CI
      0.21 to 1.13), and any atherosclerotic cardiovascular event (RR 0.63; 95% CI 0.40
      to 0.98). Among 320 subjects who used non-statin drug therapies, the RRs were
      0.66 (95% CI 0.45 to 0.97) for recurrent coronary events, 0.95 (95% CI 0.46 to
      1.95) for stroke, 0.68 (95% CI 0.35 to 1.32) for cardiovascular mortality, and
      0.77 (95% CI 0.53 to 1.11) for any atherosclerotic cardiovascular event, compared
      with untreated hyperlipidemic patients. CONCLUSIONS: In this study of MI
      survivors, the use of lipid-lowering drug therapies after hospitalization was
      associated with a reduced risk of cardiovascular events. These results emphasize
      the importance of lipid-lowering drug treatment in patients with hyperlipidemia
      who survive a first MI.

PMID- 11978148
TI  - Electrocardiographic and hemodynamic effects of Panax ginseng.
AB  - OBJECTIVE: To determine whether Panax ginseng ingestion can acutely or
      chronically alter electrocardiographic parameters: PR, QRS, QT, QTc, and RR
      intervals, and QT and QTc interval dispersion. Effects of P. ginseng on blood
      pressure and heart rate also were evaluated. METHODS: This is a prospective,
      randomized, double-blind, placebo-controlled study of healthy adults at the
      University of Connecticut. Thirty subjects were randomly allocated to receive 28
      days of therapy with either P. ginseng extract 200 mg or placebo. Baseline 12
      lead electrocardiograms (ECGs) were obtained. Subsequent ECGs were performed
      following study drug ingestion at 50 minutes, 2 hours, and 5 hours on days 1 and
      28. Blood pressure readings were taken with each ECG. RESULTS: P. ginseng
      ingestion increased the QTc interval by 0.015 seconds on day 1 at 2 hours
      compared with the placebo group (p = 0.03). It also reduced diastolic blood
      pressure from 75 +/- 5 mm Hg at baseline to 70 +/- 6 mm Hg at the same time point
      (p = 0.02). The observed effects are not believed to be clinically significant.
      No other statistically significant changes were found in electrocardiographic or
      hemodynamic variables on days 1 or 28. CONCLUSIONS: P. ginseng, at doses of 200
      mg of the extract daily, increases the QTc interval and decreases diastolic blood
      pressure 2 hours after ingestion in healthy adults on the first day of therapy.

PMID- 11978149
TI  - Substitution of generic warfarin for Coumadin in an HMO setting.
AB  - BACKGROUND: Substitution of generic warfarin for Coumadin presents safety
      concerns due to warfarin's narrow therapeutic index and because a prior generic
      formulation was removed from the US market after it was associated with adverse
      events. OBJECTIVE: To determine whether a health maintenance organization (HMO)
      can add generic warfarin to its formulary without adversely affecting warfarin
      management or increasing adverse events. DESIGN: In a prospective, observational
      study, an HMO that formerly dispensed only Coumadin added a generic warfarin
      preparation (Barr Laboratories, Pomona, NY) to its formulary. SETTING: An
      anticoagulation service (ACS) affiliated with an HMO that was based in St. Louis,
      MO. PARTICIPANTS: The cohort consisted of 182 enrollees in the ACS as of May 1,
      1999. At the start of the study, these participants were taking Coumadin; by
      October 31, 2000, all had switched to Barr warfarin. MEASUREMENTS AND MAIN
      RESULTS: We collected data 8 months prior to and 10 months after the introduction
      of generic warfarin for the following endpoints: international normalized ratio
      (INR) control, frequency of INR monitoring, number of dose changes, and rate of
      thrombotic and hemorrhagic events. Statistical process control charts were used
      to differentiate between random variation in the endpoints and changes due to
      different warfarin formulations, and we used the Wilcoxon signed-rank test to
      look for a change in any endpoint after patients changed to generic warfarin. No
      significant differences were found in any endpoint. CONCLUSIONS: Substitution of
      Barr warfarin for Coumadin did not significantly affect INR control, warfarin
      management, or adverse events. Our findings suggest that HMOs can safely
      substitute at least 1 generic formulation of warfarin without extra monitoring.

PMID- 11978150
TI  - Accuracy and precision of the CoaguChek S versus laboratory INRs in a clinic.
AB  - BACKGROUND: The CoaguChek S is the next-generation coagulation monitor for
      measuring the international normalized ratio (INR) that replaces the CoaguChek
      device. Studies are lacking comparing the CoaguChek S with local laboratory INR
      assessment to ensure its accuracy and precision for monitoring patients on
      anticoagulation. OBJECTIVE: To evaluate accuracy, precision, and technical ease
      of-use of the CoaguChek S compared with laboratory measurements. METHODS:
      Accuracy was evaluated in 101 patients by parallel assessment of INRs (CoaguChek
      S and laboratory); precision was evaluated in 31 patients using duplicate INRs
      from CoaguChek S and laboratory and from liquid quality controls. Accuracy was
      determined using orthogonal regression, Bland-Altman plot, and clinical
      applicability (INRs discrepant in categorization of INR goal and resulting in
      different therapeutic decisions). Precision was examined by comparing mean
      difference +/- SD between repeated INRs from CoaguChek S and laboratory,
      coefficient of variation (CV), and coefficient of repeatability (CR). The
      influence of low and elevated INRs on accuracy and precision was also examined.
      To assess ease-of-use of the monitor, the number of technical errors was
      recorded. RESULTS: The CoaguChek S significantly correlated to laboratory
      measurement (r = 0.93); 16.7% of INRs resulted in discrepant categorization and
      24.5% would have required a different therapeutic plan. The CV and CR compared
      well between CoaguChek S and laboratory (6% vs. 4.9%; 0.455 vs. 0.346,
      respectively). When subgroups of INR values <4.0 and <3.0 were evaluated, the
      precision improved with both methods. Precision, based on liquid quality
      controls, was good (CV 4.6% = low-level; 3.3% = high-level). The CoaguChek S was
      found to have an error rate of 1.8%. CONCLUSIONS: The CoaguChek S is an accurate
      and precise alternative to laboratory assessment of the INR at values <4.0; it is
      an efficient device with a low likelihood of errors during testing.

PMID- 11978145
TI  - Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the
      treatment of Parkinson's disease.
AB  - Current research in Parkinson's disease (PD) focuses on symptomatic therapy and
      neuroprotective interventions. Drugs that have been used for symptomatic therapy
      are levodopa, usually combined with a peripheral decarboxylase inhibitor,
      synthetic dopamine receptor agonists, centrally-acting antimuscarinic drugs,
      amantadine, monoamine oxidase-B (MAO-B) inhibitors and catechol-O
      methyltransferase (COMT) inhibitors. Drugs for which there is at least some
      evidence for neuroprotective effect are certain dopamine agonists, amantadine and
      MAO-B inhibitors (selegiline). Levodopa remains the most effective drug for the
      treatment of PD. Several factors contribute to the complex clinical
      pharmacokinetics of levodopa: erratic absorption, short half-life, peripheral O
      methylation and facilitated transport across the blood-brain barrier. In patients
      with response fluctuations to levodopa, the concentration-effect curve becomes
      steeper and shifts to the right compared with patients with stable response.
      Pharmacokinetic-pharmacodynamic modelling can affect decisions regarding
      therapeutic strategies. The dopamine agonists include ergot derivatives
      (bromocriptine, pergolide, lisuride and cabergoline), non-ergoline derivatives
      (pramipexole, ropinirole and piribedil) and apomorphine. Most dopamine agonists
      have their specific pharmacological profile. They are used in monotherapy and as
      an adjunct to levodopa in early and advanced PD. Few pharmacokinetic and
      pharmacodynamic data are available regarding centrally acting antimuscarinic
      drugs. They are characterised by rapid absorption after oral intake, large volume
      of distribution and low clearance relative to hepatic blood flow, with extensive
      metabolism. The mechanism of action of amantadine remains elusive. It is well
      absorbed and widely distributed. Since elimination is primarily by renal
      clearance, accumulation of the drug can occur in patients with renal dysfunction
      and dosage reduction must be envisaged. The COMT inhibitors entacapone and
      tolcapone dose-dependently inhibit the formation of the major metabolite of
      levodopa, 3-O-methyldopa, and improve the bioavailability and reduce the
      clearance of levodopa without significantly affecting its absorption. They are
      useful adjuncts to levodopa in patients with end-of-dose fluctuations. The MAO-B
      inhibitor selegiline may have a dual effect: reducing the catabolism of dopamine
      and limiting the formation of neurotoxic free radicals. The pharmacokinetics of
      selegiline are highly variable; it has low bioavailability and large volume of
      distribution. The oral clearance is many-fold higher than the hepatic blood flow
      and the drug is extensively metabolised into several metabolites, some of them
      being active. Despite the introduction of several new drugs to the
      antiparkinsonian armamentarium, no single best treatment exists for an individual
      patient with PD. Particularly in the advanced stage of the disease, treatment
      should be individually tailored.

PMID- 11978151
TI  - Clinical implications of endotoxin concentrations in vaccines.
AB  - BACKGROUND: A previous study suggested that high concentrations of endotoxin may
      be present in whole-cell diphtheria/tetanus/pertussis (DTP) vaccine, and the
      scientific literature contains many studies examining the reactivity of whole
      cell DTP vaccine. The medical and scientific communities have previously reported
      that the presence of endotoxin in commercial vaccines may have negative effects
      on vaccine recipients. OBJECTIVE: To determine the endotoxin concentrations in
      whole-cell DTP, acellular DTP(DTaP), and DT vaccines and determine the clinical
      experience with each vaccine. METHODS: To study the endotoxin concentrations in
      vaccines, the Limulus amebocyte lysate (LAL) assay was used. The vaccines
      analyzed with the LAL assay were whole-cell DTP vaccine lots manufactured by
      Connaught, Lederle, the Michigan and Massachusetts Departments of Health, and
      Wyeth; DTaP vaccine lots manufactured by Merieux and Takeda; and DT vaccine lots
      manufactured by Wyeth and Lederle. The incidence of adverse reactions following
      whole-cell DTP, DTaP, and DT vaccines were determined based on analysis of the
      Vaccine Adverse Events Reporting System (VAERS) database. RESULTS: The results of
      the LAL assay showed that whole-cell DTP vaccines contained considerably more
      endotoxin than either DTaP or DT vaccines. The VAERS showed that statistically
      significantly more adverse reactions were associated with whole-cell DTP vaccine
      than DTaP or DT vaccines. CONCLUSIONS: This analysis confirmed higher
      concentrations of endotoxin in whole-cell DTP vaccines compared with DTaP or DT
      vaccines. As high concentrations of endotoxin may be correlated with a higher
      incidence of adverse events, the switch from whole-cell DTP to DTaP for routine
      vaccinations in the US seems well justified.

PMID- 11978152
TI  - Effect of therapeutic class on counseling in community pharmacies.
AB  - OBJECTIVE: To assess the effect and importance of the therapeutic class of a drug
      as a determinant for verbal counseling by community pharmacists. METHODS: Direct
      external observations (n = 1431) of pharmacist-customer interactions at the point
      of delivery of prescription medicines were conducted in 7 community pharmacies in
      Finland. Trained observers noted whether the pharmacist provided information on
      directions for use, mode of action, and adverse effects. To examine factors
      associated with counseling, a multiple logistic regression analysis was
      constructed, with the dependent variable being counseling of any of the 3
      observed topics. In addition to therapeutic class, other independent variables
      were the pharmacy; pharmacist's age, gender, and degree; and the customer's age,
      gender, previous use of medicine, and question asking. RESULTS: Provision of
      counseling differed significantly according to therapeutic classes. Counseling on
      any of the 3 observed topics was most likely to be provided for customers with
      antibiotics (80%) and least likely for customers with gynecologic preparations
      (18%). Differences between therapeutic classes remained statistically significant
      when the effects of the other variables were controlled for. Other significant
      predictors for any verbal counseling were the pharmacy, customer's previous use
      of the medicine, and question asking. CONCLUSIONS: Therapeutic class is an
      important variable that should be included in further studies and considered when
      comparing studies on patient counseling in community pharmacies.

PMID- 11978153
TI  - Assessment of an online consumer "Ask Your Pharmacist" service.
AB  - OBJECTIVE: To describe consumer demographics and the types of questions submitted
      to an online Ask Your Pharmacist (AYP) drug information service. METHODS: This is
      a retrospective review of a sample of consecutive queries submitted online to an
      AYP service between 1999 and 2000. All data were coded, transcribed, and
      evaluated in a Microsoft Excel spreadsheet. Data regarding gender, age, patient
      relationship to consumer, allergies, medical conditions, products, and question
      types were evaluated. RESULTS: One thousand eighty-seven queries involving drug
      information or health-related questions were evaluated: 65% of the queries were
      from consumers requesting information for themselves; 55.2% of queries originated
      from women; 61% of consumers were between 19 and 55 years of age. The 5 most
      listed medical conditions were depression-related, hypertension, allergies, pain,
      and infectious disease. More than 60% of the questions involved prescription or
      over-the-counter (OTC) medications; another 10% targeted herbal products or
      dietary supplements. Consumers were most interested in drug efficacy, safety, and
      drug interactions. CONCLUSIONS: An AYP online service is a relatively new, unique
      way for consumers to receive medication information. Consumers of all ages use
      AYP services for both acute and chronic conditions. Most consumers asked
      questions related to their own health or medications. Consumers were more likely
      to ask questions related to prescription and OTC medications than to botanical
      and dietary supplements. Consumers were primarily interested in drug efficacy and
      adverse effects.

PMID- 11978154
TI  - Geriatric drug therapy and healthcare utilization in the United kingdom.
AB  - OBJECTIVE: To describe the use of prescription drug therapy, especially
      polypharmacy, in an elderly general population; to relate that use to age,
      gender, and different types of healthcare utilization; and to investigate the
      influence of selection of different time windows on the result of the quantity as
      well as the categories of drugs used. METHODS: Data on a sample of 5000 patients
      aged 65-90 years in 1996 were derived from the General Practice Research Database
      (GPRD). The population covered by GPRD is broadly representative of the UK
      population treated in general practice. Drug use was assessed using 2 time
      windows - current use of individual drugs on a random day (index date) and 1
      month following the index date. Healthcare utilization was analyzed by use of
      information on visits to general practitioners (GPs), hospitalizations, and
      referrals to specialists. RESULTS: Women used more drugs than men; however, the
      prevalence of polypharmacy, defined as concomitant use of > or =5 drugs, was
      similar in both genders. The most frequently used therapeutic groups were
      cardiovascular, central nervous, and gastrointestinal system drugs. Almost 80% of
      both women and men visited a GP at least once a year. Overall, women used more
      ambulatory care services and men were hospitalized more often. Use of random date
      compared with 1-month period resulted in a significant underestimation of the
      amount of drugs used for acute conditions and, consequently, the risk of
      polypharmacy. CONCLUSIONS: The overall results confirm the findings in earlier
      studies suggesting that the GPRD might be a useful tool in further studies on
      prescription drug use among elderly persons. More information on the
      appropriateness of drug use is needed to prevent overuse as well as underuse of
      medications among the elderly.

PMID- 11978155
TI  - Influence of socioeconomic status on drug selection for the elderly in Canada.
AB  - OBJECTIVE: To examine the association between socioeconomic status, as indicated
      by neighborhood median income levels, and physician drug selection between older,
      less expensive generic drugs and newer, more expensive brand-name drugs for
      elderly patients initiating drug therapy in a universal healthcare system.
      METHODS: We conducted a population-based, retrospective, cross-sectional study.
      Using healthcare administrative databases, we assessed the medication profiles of
      128 314 patients from more than 1.4 million residents of Ontario > or =65 years
      old initiating antipsychotic, hydroxymethylglutaryl-coenzyme A reductase
      inhibitor (statin), or ocular beta-blocker drug therapy from January 1, 1998,
      through December 31, 1999. We examined the selection of older generic drugs
      relative to newer brand-name agents for patients in each of 5 income quintiles.
      RESULTS: Overall, brand-name drug prescribing modestly increased with increasing
      income quintile after adjusting for patient age and gender (61.2% in the lowest
      income quintile vs. 64.1% in the highest income quintile; p value for trend <
      0.001). Significant risk ratios comparing the highest with the lowest income
      quintile patients were observed for selection of newer, brand-name antipsychotics
      (RR 1.14; 95% CI 1.06 to 1.23), older generic statins (RR 0.86; 95% CI 0.77 to
      0.95), and newer, brand-name ocular beta-blockers (RR 1.13; 95% CI 1.02 to 1.25).
      CONCLUSIONS: This study suggests that income-related differences in treatment
      selection by physicians may exist. The reasons for these differences and
      subsequent impact on health outcomes warrant further investigation.

PMID- 11978156
TI  - Lansoprazole-induced thrombocytopenia.
AB  - OBJECTIVE: To describe a case of thrombocytopenia associated with the
      administration of lansoprazole. CASE SUMMARY: An 85-year-old white man presented
      with an upper gastrointestinal hemorrhage from a gastric ulcer. His platelet
      count was normal on admission. He was started on oral lansoprazole 60 mg twice
      daily and, on hospital day 2, his platelet count decreased to 102 x 10(3)/mm(3);
      on hospital day 3, the platelet count was 36 x 10(3)/mm(3). Lansoprazole was
      discontinued, and the platelet count returned to normal. He has not had any
      further episodes of thrombocytopenia to date. DISCUSSION: After exclusion of
      other causes, the onset of thrombocytopenia after administration of lansoprazole,
      the resolution of the adverse reaction after discontinuation of the drug, and the
      fact that no other medicines were introduced during this time frame lead us to
      believe that this was most likely an idiosyncratic thrombocytopenic response to
      lansoprazole. To date, this is the first reported case of what appears to be
      isolated thrombocytopenia associated with lansoprazole. CONCLUSIONS: Clinicians
      should be aware of the possible association of thrombocytopenia with lansoprazole
      and discontinue the drug if thrombocytopenia becomes apparent.

PMID- 11978157
TI  - Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a
      proton-pump inhibitor.
AB  - OBJECTIVE: To report a case of vitamin B(12) deficiency associated with long-term
      use (approximately 4 1/2 y) of histamine(2) (H(2))-receptor antagonists and a
      proton-pump inhibitor (PPI) in a patient with gastroesophageal reflux. CASE
      SUMMARY: A 78-year-old nonvegetarian white woman with symptomatic
      gastroesophageal reflux (GER) was started on cimetidine 300 mg 4 times daily in
      February 1990 and took various other antisecretory medications over the course of
      the next 4 1/2 years. She had a normal serum vitamin B(12) concentration of 413
      pg/mL in August 1992. In June 1994, her serum vitamin B(12) concentration was
      found to be in the low normal range at 256 pg/mL. Biochemical markers of vitamin
      B(12)-dependent enzyme activity were measured at that time, and methylmalonic
      acid (MMA) and homocysteine (HCYS) were elevated at 757 nmol/L and 27.3
      micromol/L, respectively. Serum folate was within the normal range at 4.9 ng/mL,
      and serum creatinine was slightly elevated at 1.4 mg/dL. MMA and HCYS
      concentrations decreased dramatically with oral replacement of vitamin B(12) 1000
      microg/d, which confirmed vitamin B(12) deficiency. Oral replacement also
      demonstrated that the woman was able to adequately absorb nonprotein-bound
      vitamin B(12) from the gastrointestinal tract, suggesting that her deficiency was
      a result of food-cobalamin malabsorption. The accumulation of MMA and HCYS was
      not a consequence of renal dysfunction, since both metabolites dramatically
      decreased with vitamin B(12) replacement. DISCUSSION: Malabsorption of dietary
      protein-bound vitamin B(12) has been demonstrated with the use of H(2)-receptor
      antagonists and PPIs. One previous case report of vitamin B(12) deficiency
      resulting from long-term use of omeprazole has been published. The malabsorption
      of dietary vitamin B(12) is thought to be a result of its impaired release from
      food protein, which requires gastric acid and pepsin as the initial step in the
      absorption process. CONCLUSIONS: The use of H(2)-receptor antagonists and/or PPIs
      may impair the absorption of protein-bound dietary vitamin B(12) and could
      contribute to the development of vitamin B(12) deficiency with prolonged use.
      Patients taking these medications for extended periods of time, particularly >4
      years, should be monitored for vitamin B(12) status.

PMID- 11978158
TI  - Tolterodine-associated acute mixed liver injury.
AB  - OBJECTIVE: To report a patient with an acute mixed liver injury associated with
      tolterodine therapy. CASE SUMMARY: An 81-year-old white woman with urge
      incontinence experienced malaise, fever, and gastrointestinal disturbances 18
      days after starting tolterodine 2 mg twice daily. The patient's concurrent
      medications included flunitrazepam, diclofenac, and dorzolamide/timolol eye
      drops. Laboratory examination was consistent with the presentation of an acute
      mixed liver injury with increased transaminase enzymes, alkaline phosphatase,
      gamma-glutamyltransferase, and bilirubin. Additionally, she had mild leukocytosis
      with eosinophilia. After tolterodine was discontinued, the abnormal liver and
      hematologic parameters returned to normal within 4 weeks. DISCUSSION:
      Tolterodine, a muscarinic receptor antagonist, has predominantly anticholinergic
      effects. To our knowledge, this is the first case published describing
      tolterodine-associated acute mixed liver injury. However, some of the patient's
      additional symptoms can also be considered part of a drug-induced
      hypersensitivity syndrome. This is usually defined by the triad of fever,
      cutaneous reaction, and involvement of internal organs, mainly affecting the
      liver. The close temporal relationship between the start of tolterodine therapy
      and the first symptoms and the reversibility after dechallenge led us to conclude
      that the adverse reaction was possibly related to tolterodine exposure.
      CONCLUSIONS: Our case illustrates that tolterodine may rarely be associated with
      liver injury. This may have been an organ manifestation of tolterodine-induced
      hypersensitivity syndrome.

PMID- 11978159
TI  - Rhabdomyolysis after concomitant use of cyclosporine, simvastatin, gemfibrozil,
      and itraconazole.
AB  - OBJECTIVE: To report a case of rhabdomyolysis in a patient receiving
      cyclosporine, simvastatin, gemfibrozil, and itraconazole. CASE REPORT:
      Rhabdomyolysis occurring in transplant patients receiving both cyclosporine and
      the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin has
      been well documented. The exact mechanism by which this interaction leads to
      rhabdomyolysis is unknown. Experience with newer agents of the statin drug class
      in transplant patients is limited. Since the interaction between cyclosporine and
      HMG-CoA reductase inhibitors involves the CYP3A4 enzyme system, the possibility
      of amplifying this interaction exists when other drugs affecting the same enzyme
      system are coprescribed. We describe a case in which a heart transplant recipient
      stable on a drug regimen that included cyclosporine, simvastatin, and gemfibrozil
      developed rhabdomyolysis after initiation of the antifungal agent itraconazole.
      DISCUSSION: Drug-drug interactions due to shared metabolism via the CYP3A4
      pathway can result in significant adverse outcomes. This article discusses
      concurrent use of an HMG-CoA reductase inhibitor with other drugs that inhibit
      the CYP3A4 isoenzyme, leading to a case of possible fatal rhabdomyolysis.
      CONCLUSIONS: Clinicians must be aware of drugs metabolized via cytochrome P450
      isoenzymes and identify those requiring risk-versus-benefit analysis before
      prescribing. Patients need to be educated as to signs and symptoms requiring
      immediate physician intervention.

PMID- 11978160
TI  - Colchicine-induced rhabdomyolysis.
AB  - OBJECTIVE: To report a case of rhabdomyolysis occurring during treatment with
      colchicine. CASE SUMMARY: A 44-year-old African American man was admitted to the
      hospital due to persistent diarrhea, vomiting, and diffuse weakness. Past medical
      history was significant for renal failure requiring peritoneal dialysis, gout,
      and a new skin lesion. Approximately 2 months prior to admission, he had been
      started on colchicine and allopurinol. Creatine kinase concentration on admission
      was >14 000 U/L. Liver function tests were elevated 5 times the upper limit of
      normal. Colchicine was discontinued on admission. Creatine kinase concentrations
      decreased significantly, and strength and ambulation improved throughout
      hospitalization. DISCUSSION: Colchicine was thought to be the causative factor
      for rhabdomyolysis in conjunction with chronic renal failure and elevated liver
      function tests. After discontinuation of colchicine, creatinine kinase
      concentrations declined and the patient's ability to walk improved. Limited case
      reports of colchicine-induced rhabdomyolysis have been published. CONCLUSIONS:
      Chronic renal failure in conjunction with elevated liver function tests appear to
      increase the possibility of colchicine-induced toxicity, specifically,
      rhabdomyolysis.

PMID- 11978161
TI  - Extrapyramidal symptoms with ritonavir/indinavir plus risperidone.
AB  - OBJECTIVE: To report a case of suspected extrapyramidal symptoms (EPS) in a
      patient initiated on ritonavir and indinavir while taking risperidone for a tic
      disorder. CASE SUMMARY: A 35-year-old white man with AIDS received risperidone 2
      mg twice daily for treatment of a Tourette's-like tic disorder. Ritonavir and
      indinavir were initiated, and 1 week later, he experienced significantly impaired
      swallowing, speaking, and breathing, and worsening of his existing tremors.
      Ritonavir and indinavir were discontinued. On the same day, the patient increased
      the risperidone dosage to 3 mg twice daily. Symptoms continued to worsen over the
      next 3 days. All investigations and laboratory parameters were unremarkable, and
      vital signs were stable. Risperidone was discontinued and clonazepam initiated.
      Three days later, the patient's symptoms were significantly improved. DISCUSSION:
      The symptoms described herein are consistent with neuroleptic-induced acute
      dystonia and potentially neuroleptic-induced parkinsonism. We believe this
      adverse effect occurred as a result of a drug interaction between
      ritonavir/indinavir and risperidone. Based on the pharmacokinetics of these
      medications, we hypothesize that inhibition of CYP2D6 and CYP3A4 by ritonavir and
      indinavir may have resulted in an accumulation of the active moiety of
      risperidone, which may explain the occurrence of EPS in this patient.
      CONCLUSIONS: This is the second published case report describing a suspected drug
      interaction with ritonavir, indinavir, and risperidone. Caution is warranted when
      risperidone is prescribed with ritonavir/indinavir, and possibly with other
      antiretrovirals that inhibit the same pathways.

PMID- 11978162
TI  - Probable metabolic interaction of doxifluridine with phenytoin.
AB  - OBJECTIVE: To report the marked elevation of the serum phenytoin concentration
      during treatment with antineoplastic agents. CASE SUMMARY: A 51-year-old Japanese
      woman, who was diagnosed with multiple brain metastatic tumors, was placed on
      oral phenytoin at a maintenance dose of 200 mg/d (3.8 mg/kg/d) to prevent
      seizures. The serum concentration of phenytoin was well controlled within the
      therapeutic range; no seizures occurred. Four months later, combination therapy
      with doxifluridine (5'-DFUR) 800 mg/d, cyclophosphamide 100 mg/d, and
      medroxyprogesterone acetate 800 mg/d was initiated because of further metastasis.
      Approximately 1 month after the start of concurrent treatment with the
      antineoplastic agents, the serum phenytoin concentration was elevated to fourfold
      of the original concentration. Staggering was observed at that time, but toxic
      symptoms gradually subsided with the decline in the serum phenytoin concentration
      after its withdrawal. DISCUSSION: A probable explanation for the marked elevation
      of serum phenytoin concentration is a reduction of the capacity of CYP2C
      dependent phenytoin metabolism, and the antineoplastic agents could be involved
      in this event. The interaction of fluorouracil and phenytoin is known in clinical
      practice, and it is reported that the expression of hepatic CYP2C enzymes is
      depressed by exposure of rats to fluorouracil. 5'-DFUR, a prodrug of
      fluorouracil, was considered the likeliest candidate responsible for the
      interaction. This interaction was of clinical significance because of the great
      extent of changes in the serum phenytoin concentration. CONCLUSIONS: Clinicians
      should be aware of the elevation of serum phenytoin concentrations when phenytoin
      is given in combination with fluorouracil derivatives, including 5'-DFUR.

PMID- 11978163
TI  - Pharmacokinetic analysis of theophylline to assess noncompliance in therapy.
AB  - OBJECTIVE: To report a case showing patient noncompliance, supported by outcomes
      of pharmacokinetic analysis of theophylline as a surrogate drug. CASE SUMMARY: A
      45-year-old woman with severe hypertension was treated with a variety of oral
      antihypertensive drugs, but there was no improvement in her elevated blood
      pressure. Since we suspected that her intestinal drug absorption capacity was
      impaired, a theophylline absorption test was performed. When oral theophylline
      was given to the patient in tablet form, the apparent bioavailability was only
      20%, which agreed with our hypothesis. However, the bioavailability of
      theophylline given in liquid form was almost 100%, and theophylline in tablet
      form was confirmed to be fully bioavailable when the test was performed under
      supervision by medical staff. DISCUSSION: The almost complete bioavailability of
      oral theophylline indicated that there was no impairment in intestinal absorption
      capacity. The low bioavailability of theophylline observed after tablet
      administration in the first trial was apparently a result of noncompliance,
      because the staff did not supervise administration to ensure that tablets were
      swallowed. Thus, the low response to antihypertensive therapy was attributed to
      patient noncompliance in taking the drugs, despite her insistence to the
      contrary. CONCLUSIONS: The use of theophylline was a novel approach to evaluating
      the absorbability of orally administered drugs in a patient suspected of poor
      compliance with therapy. A great difference in theophylline bioavailability
      between the supervised and unsupervised trials was strongly indicative of patient
      noncompliance. The possibility of impaired absorption was virtually ruled out.

PMID- 11978165
TI  - Safety of zaleplon in the treatment of insomnia.
AB  - OBJECTIVE: To evaluate the safety of zaleplon, a quick-acting, rapidly eliminated
      nonbenzodiazepine (non-BZD) hypnotic, as described in clinical investigations of
      adult and/or elderly subjects. DATA SOURCES: Published and presented studies
      evaluating zaleplon, a novel non-BZD, were identified via MEDLINE (1995-July
      2001), Current Contents (ISI database), bibliographic reviews, and consultation
      with sleep specialists who also identified published abstracts containing data
      not yet published in peer-reviewed journals. DATA SYNTHESIS: Transient and
      chronic insomnia are common problems that should be clinically evaluated and
      appropriately treated. BZDs have been a primary pharmacotherapy for treating
      insomnia, despite their disadvantages. Newer hypnotics, characterized by
      increased receptor-binding specificity and favorable pharmacokinetics, provide
      potentially better alternatives to BZDs. Assessments included residual sedation,
      psychomotor impairment, or cognitive dysfunction during treatment, as well as the
      occurrence of rebound insomnia and withdrawal effects after discontinuation of
      therapy. CONCLUSIONS: Zolpidem, the first non-BZD hypnotic, appears to have short
      and long-term safety profiles similar to those of the BZD triazolam. Zaleplon, a
      newer non-BZD sleep medication, has a quick onset of action and undergoes rapid
      elimination, which results in a better safety profile than previously available
      agents. Additionally, rebound insomnia and other withdrawal effects have not been
      demonstrated with zaleplon, and the drug is well tolerated in both young and
      elderly patients. These characteristics may be clinically advantageous for
      patients who should not receive BZDs.

PMID- 11978164
TI  - Ziprasidone: the fifth atypical antipsychotic.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and
      adverse effects of ziprasidone as a treatment for schizophrenia. DATA SOURCES:
      Information was selected from a MEDLINE search (July 2000-October 2001) of
      English-language medical literature using ziprasidone as the search term. Manual
      searches of pertinent journal article references, request for medical information
      from Pfizer, and access of the Web site of the Food and Drug Administration were
      also performed. STUDY SELECTION: All available published information regarding
      the pertinent characteristics of ziprasidone were considered for selection. DATA
      EXTRACTION: Pharmacology and pharmacokinetic studies were selected to provide a
      comprehensive description of these characteristics. Clinical investigations were
      evaluated for design, sample size, diagnosis, duration, and outcome. Data from
      all investigations were selected by 1 author and reviewed by both authors. DATA
      SYNTHESIS: Ziprasidone is a benzisothiazolyl piperazine-type atypical
      antipsychotic that shares the serotonin(2A)/dopamine(2) (5-HT(2A)/D(2)) profile
      of the available atypical antipsychotics. Ziprasidone has demonstrated in vitro
      activity as a 5-HT(1A) receptor agonist and as a very weak inhibitor of serotonin
      and norepinephrine reuptake. These data do not support ziprasidone as being a
      clinically meaningful inhibitor of serotonin/norepinephrine reuptake. Oral
      bioavailability of ziprasidone taken with food is approximately 60%, half-life is
      approximately 6-7 hours, and protein binding is extensive at >99%. Twelve
      metabolites have been identified, yet only 4 of these are considered to be
      primary metabolites. Metabolism of ziprasidone by aldehyde oxidase produces its
      only metabolite with potential pharmacologic activity; CYP3A4 also contributes to
      the metabolism of ziprasidone. Clinical studies support ziprasidone as
      efficacious for the treatment of patients with acute exacerbations of
      schizophrenia or schizoaffective disorder. Daily doses permitted in these
      clinical trials ranged from 40 to 160 mg, but only doses between 120 and 160 mg/d
      have been superior to placebo. Future research efforts should be directed toward
      refractory schizophrenia, cognitive impairment in schizophrenia, affective and
      anxiety symptoms associated with schizoaffective disorder, and bipolar disorder.
      Adverse effect characteristics of ziprasidone commonly include headache, nausea,
      and somnolence; infrequent effects include extrapyramidal symptoms and weight
      gain. Ziprasidone has been reported to cause an average QTc prolongation of
      approximately 20 msec; there have only been 2 patients (0.06%) reported by the
      manufacturer to have a measured QTc interval >500 msec. CONCLUSIONS: Ziprasidone
      is a safe and efficacious atypical antipsychotic for the acute management of
      schizophrenia. Efficacy data and most safety data for ziprasidone support its use
      as a first-line treatment for schizophrenia; however, its potential effects on
      ventricular repolarization relegate it to second-line status in patients with
      comorbid cardiovascular risks.

PMID- 11978167
TI  - Methodology to determine duration of action for antihypertensive drugs.
AB  - OBJECTIVE: To review and comment on methods used to assess the duration of action
      of antihypertensive drugs. DATA SOURCES: A MEDLINE search (1966-June 2000) using
      key terms such as trough-to-peak ratio and ambulatory blood pressure monitoring
      was conducted. STUDY SELECTION: An article was considered for this review if it
      pertained to the assessment of the duration of action of antihypertensive drugs.
      Special attention was given to articles dealing with methodologic aspects. DATA
      SYNTHESIS: Antihypertensive drugs with a long duration of action are thought to
      provide better therapeutic coverage against hypertensive complications compared
      with that of short-acting agents. Measuring blood pressure at the end of the
      dosing interval may be a way to assess the duration of action of a drug. However,
      the use of high doses of a short-acting agent to obtain sufficient effect when at
      trough concentrations can potentially cause dose-related adverse effects at the
      peak time, contributing to nonadherence to therapy and thus to adverse outcomes.
      To alleviate this problem, the US Food and Drug Administration (FDA) has
      conceptualized the trough-to-peak (T:P) ratio. Although this arithmetic index has
      since been widely used to characterize the duration and safety of blood pressure
      control achieved by antihypertensive agents, several methodologic flaws limit its
      interpretation in the clinic. Ambulatory blood pressure monitoring (ABPM) is a
      more reliable approach to assess the duration of action and outcome of
      antihypertensive therapy. CONCLUSIONS: Different methodologic approaches exist to
      evaluate the duration of action of antihypertensive drugs. Although the T:P ratio
      has been suggested by the FDA, it is difficult to establish a fair comparison
      among various antihypertensive agents based solely on this index. Treatment
      evaluation based on ABPM may be preferable to those guided by T:P because ABPM is
      more reproducible and is now established as a predictor of cardiovascular risk.

PMID- 11978166
TI  - Lamotrigine update and its use in mood disorders.
AB  - OBJECTIVE: To provide a qualitative, systematic update and review of the
      pharmacology, pharmacokinetics, efficacy in mood disorders, adverse effects, and
      costs of lamotrigine. DATA SOURCES: Citations obtained from MEDLINE searches
      (1985-September 2001) using lamotrigine as a text word, articles identified in
      reference lists of pertinent articles, abstracts presented at conferences, and
      research data from GlaxoSmithKline. DATA EXTRACTION: English-language articles
      were considered for possible inclusion. Each title and abstract was examined to
      determine whether the publication contained up-to-date information relevant to
      the objective. Twenty clinical trials that provided data on response rates in
      mood disorders were tabulated. DATA SYNTHESIS: Lamotrigine's primary action is to
      modulate voltage-gated sodium channels. Evidence suggests that it decreases
      glutamate transmission, directly reduces calcium influx, mildly blocks
      transmitter reuptake, and alters intracellular mechanisms of resting transmitter
      release. The average half-life of lamotrigine is approximately 24 hours, but
      decreases to approximately 7.4 hours when used concurrently with phenytoin, and
      increases to approximately 59 hours with valproic acid. Seven of the 20 clinical
      trials were randomized, double-blind, and controlled. Existing data are
      inadequate to evaluate lamotrigine use in major depression. The pooled response
      rates for patients with depressed, manic, mixed, and rapid cycling bipolar
      disorder were similar, ranging from 52% to 63%. Adverse effects are infrequent
      when the drug is used alone, but become more frequent when lamotrigine is
      combined with other anticonvulsants. While most rashes are mild, approximately 1
      in 500 patients develops exfoliative dermatitis. A slow upward dose titration is
      recommended to reduce the incidence of serious rash, but this may delay the
      attainment of adequate dosage for 6 weeks. Lamotrigine has positive effects on
      cognitive function, but occasionally produces insomnia. Lamotrigine costs 2-4
      times more than lithium, carbamazepine, and generic valproic acid. CONCLUSIONS:
      When efficacy, adverse effects, and cost are considered, lamotrigine should
      probably be reserved as a second-line agent for bipolar depression.

PMID- 11978168
TI  - Continuous infusion of coagulation factor products.
AB  - OBJECTIVE: To review clinical information related to the use of continuous
      infusion factor products in patients with hemophilia. Specifically, case reports
      and open-label trials are summarized involving the use of factor VIII and
      recombinant factor VIIa for a variety of indications including surgical
      prophylaxis, acute bleeding, primary prevention, and management of inhibitors. In
      addition, issues surrounding the use of continuous infusion of factor products
      such as pharmacokinetic rationale, stability/sterility, and cost are reviewed.
      DATA SOURCES: Primary and review articles were identified through a MEDLINE
      search (1990-June 2001) and through secondary sources. STUDY SELECTION AND DATA
      EXTRACTION: All articles identified from the data sources were evaluated, and all
      information deemed relevant was included in this review. DATA SYNTHESIS: Data
      concerning the administration of factor products are primarily detailed in open
      label trials and case reports. Comparisons between intermittent bolus injections
      and continuous infusion of factor products are limited and primarily compare
      continuous infusion regimens with historical controls. The rationale behind the
      continuous-infusion approach is linked to the pharmacokinetics of factor products
      administered via this route. Pharmacokinetic data reveal that, with continuous
      infusion of factor products, a reduction in clearance and a maintenance of factor
      serum concentrations are noted. CONCLUSIONS: Administration of factor products
      (factor VIII and recombinant factor VIIa) via continuous infusion has produced
      favorable hemostatic effects compared with intermittent bolus injections. The
      advantages of continuous infusion include maintenance of a constant factor
      concentration, thereby reducing risk of bleeding from excessively low trough
      concentrations, and a decrease in factor consumption related to a reduction in
      factor clearance with constant infusion. Manufacturers recommend using
      reconstituted factor products either immediately or within 1-3 hours after
      reconstitution; however, several studies have found the products to be stable and
      sterile for longer periods.

PMID- 11978169
TI  - Development of a pharmacist-managed lipid clinic.
AB  - OBJECTIVE: To describe the development of a pharmacist-managed lipid clinic
      within a primary care medical clinic and review its results after approximately
      12 months of operation. METHODS: A pharmacist-managed lipid clinic was developed
      at Naval Medical Center San Diego. Administrative background, treatment algorithm
      development, operational issues, clinical activities, and barriers to the clinic
      are discussed. For intermediate outcomes, data from patients who had at least 1
      intervention by the pharmacist and 1 follow-up lipid panel were analyzed for
      medication use, changes in lipid parameters, and percent reaching the low-density
      lipoprotein (LDL) target goal. Modified National Cholesterol Education Program
      Adult Treatment Panel II guidelines were used to determine the LDL goal. RESULTS:
      Following approximately 12 months of operation, the clinic received 204 referrals
      and consisted of 146 active patients. A brief study was conducted to assess
      clinical outcomes. Of 115 patients who were seen in the clinic and met inclusion
      criteria, 57% were receiving treatment with a hydroxymethylglutaryl coenzyme A
      reductase inhibitor (statin) and 17% were receiving fibrates; 17% of the patients
      were not receiving lipid-lowering medications. Relative to baseline, LDL
      cholesterol concentrations decreased 20%, high-density-lipoprotein cholesterol
      increased 11%, and triglycerides decreased 19%. Overall, LDL goals were reached
      in 77% of the patients. LDL goals were attained by 63%, 79%, and 93% of patients
      with targets of <100, <130, and <160 mg/dL, respectively. Results are compared
      with other studies regarding lipid goal attainment. CONCLUSIONS: A pharmacist
      managed lipid clinic can be developed and integrated into a primary care medical
      clinic. Pharmacists can effectively manage lipid-lowering therapy, helping to
      achieve LDL goals.

PMID- 11978170
TI  - Flavopiridol, a novel cyclin-dependent kinase inhibitor, in clinical development.
AB  - OBJECTIVE: To review preclinical and clinical information on flavopiridol, an
      inhibitor of cyclin-dependent kinases (CDKs), tested as an antitumor agent. DATA
      SOURCES: Primary and review articles were identified by MEDLINE search (1990-June
      2001). Abstracts from recent meetings were also used as source materials. DATA
      EXTRACTION: Flavopiridol was reviewed with regard to its mechanisms, preclinical
      and clinical results, pharmacokinetics, and metabolism. DATA SYNTHESIS:
      Flavopiridol is an inhibitor of several CDKs and displays unique anticancer
      properties. In addition to direct CDK inhibition, flavopiridol also exhibited
      other features such as inducing apoptosis in many cancer cell lines, decreasing
      cyclin D1 concentration, and inhibiting angiogenesis. Preclinical xenograft
      models showed significant antitumor activity for flavopiridol. The regimen using
      72-hour continuous infusion every 2 weeks has been most extensively applied in
      clinical trials, with a 1-hour infusion currently being explored to achieve
      higher peak concentrations. Several Phase I and II trials have been reported,
      with some evidence of antitumor activity noted. Further Phase I and II trials
      using flavopiridol as a single agent and in combination with standard
      chemotherapeutic regimens and various tumor types are ongoing. CONCLUSIONS:
      Flavopiridol is the first CDK inhibitor to enter clinical trials. Several Phase I
      and Phase II clinical trials with different regimens (72-h or 1-h infusion) have
      been completed. Initial clinical trials have been intriguing, but many questions
      remain: What is the best regimen (< or =72-h infusion)? Does optimal future
      development of this drug depend on the combination with other chemotherapy? What
      is the best combination of flavopiridol with other chemotherapy?

PMID- 11978172
TI  - Therapeutic drug monitoring of lamotrigine.
AB  - OBJECTIVE: To evaluate the usefulness of routine monitoring of serum lamotrigine
      concentration. DATA SOURCE: Literature was accessed through MEDLINE (1990-January
      2001). Key search terms included lamotrigine, pharmacokinetics, and epilepsy.
      DATA SYNTHESIS: A decision-making algorithm was used to evaluate the clinical
      evidence to support or refute the routine use of serum lamotrigine concentrations
      to adjust doses. The value of serum lamotrigine concentration monitoring remains
      controversial, primarily because clear relationships between concentration and
      pharmacologic response (either efficacy or toxicity) have not been demonstrated.
      CONCLUSIONS: Serum concentration monitoring of lamotrigine is not recommended as
      a tool for routine dose adjustment.

PMID- 11978171
TI  - Combination drug therapy for gastroesophageal reflux disease.
AB  - OBJECTIVE: To evaluate the role of combination therapy with proton-pump
      inhibitors (PPIs) and histamine(2) receptor antagonists in gastroesophageal
      reflux disease (GERD). DATA SOURCES: Clinical literature identified through
      MEDLINE (January 1966-August 2001). Key search terms included gastroesophageal
      reflux, benzimidazoles; omeprazole; lansoprazole; pantoprazole; rabeprazole;
      receptor antagonists, histamine(2); therapy, combination drug; therapy, combined
      modality; and combinations, drug. DATA SYNTHESIS: Approximately 80-90% of
      patients show healing of reflux esophagitis after 8 weeks of once-daily PPI
      therapy. Patients taking PPI therapy twice daily still have nocturnal acid
      breakthrough (periods of gastric pH <4 lasting for > or =60 min during the night)
      as much as 70% of the time. The clinical application of this finding has not been
      shown. One trial has shown that omeprazole in the morning plus ranitidine at
      bedtime is not as effective as omeprazole twice daily given before the morning
      and evening meals at controlling nocturnal acid breakthrough. Further, 1 small
      trial in healthy subjects without GERD showed that the addition of a 1-time dose
      of ranitidine at bedtime to a twice-daily regimen of omeprazole may decrease the
      occurrence of nocturnal acid breakthrough. However, the clinical significance of
      this finding is not clear. CONCLUSIONS: No studies in patients with GERD
      demonstrate that the addition of histamine(2) receptor antagonists to twice-daily
      PPI therapy provides any further benefit above that derived from PPIs alone. The
      parameter used to measure the efficacy of combination regimens for GERD thus far-
      nocturnal acid breakthrough--has not been proven to correlate with improvement of
      GERD symptoms in any controlled or prospective clinical trials. Further
      investigation is needed to determine optimal therapy in patients refractory to
      standard doses of PPIs.

PMID- 11978173
TI  - Herbal supplement PC-Spes for prostate cancer.
AB  - OBJECTIVE: To determine the efficacy and toxicity of the herbal supplement PC
      Spes in prostate cancer patients. METHODS: Literature search through MEDLINE
      (1966-October 2001), PubMed, and abstracts from the Annual Meeting of the
      American Society of Clinical Oncology (1995-2001). RESULTS: PC-Spes was
      associated with biochemical and clinical response in some prostate cancer
      patients. The mechanisms of action of PC-Spes appeared to be related to its
      estrogenic activity. CONCLUSIONS: PC-Spes is associated with some efficacy in
      prostate cancer patients. Due to the limited data available, it should not be
      used to replace standard androgen suppression therapy in androgen-dependent
      patients. PC-Spes may have a role for patients who have failed standard
      treatments for androgen-independent disease and have no history of
      thromboembolism or abnormal bleeding. PC-Spes has a toxicity profile similar to
      those of androgen suppression and estrogen therapy.

PMID- 11978174
TI  - Clinical pharmacy in a South Indian teaching hospital.
AB  - OBJECTIVE: To describe how clinical pharmacy is helping to improve medication use
      at a South Indian teaching hospital by addressing medication use problems, which
      are commonly encountered in India. SUMMARY: Clinical pharmacy is practiced in
      many countries and makes a significant contribution to improved drug therapy and
      patient care. India is a country with significant problems with medication use,
      but until recently Indian pharmacists have not been educated for a patient-care
      role. Postgraduate pharmacy practice programs have been established at 2 pharmacy
      colleges in South India as a result of a joint Indo-Australian program of
      cooperation. At a teaching hospital associated with the colleges, clinical
      pharmacy services such as drug information, medication counseling, drug therapy
      review, adverse drug reaction reporting, and the preparation of antibiotic
      guidelines are assisting clinicians to improve drug therapy and patient care.
      Seven hundred twenty-seven requests for drug information were received from July
      1997 to February 2001, and 543 suspected adverse drug reactions were evaluated
      from November 1997 to February 2001. The most common drug classes causing adverse
      drug reactions were antibiotics, nonsteroidal antiinflammatory drugs, and
      antitubercular agents. Physician opinion and service utilization have also been
      surveyed: 82% of respondents had sought drug information from the Clinical
      Pharmacy Department and 71% of respondents had sought advice on individual
      patient management. The success of this program is raising awareness of clinical
      pharmacy among pharmacy educators elsewhere in India and has led to the
      introduction of clinical pharmacy services at other Indian hospitals.

PMID- 11978175
TI  - Biochemical adaptations of two sugar kinases from the hyperthermophilic archaeon
      Pyrococcus furiosus.
AB  - The hyperthermophilic archaeon Pyrococcus furiosus possesses a modified Embden
      Meyerhof pathway, including an unusual ADP-dependent glucokinase (ADP-GLK) and an
      ADP-dependent phosphofructokinase. In the present study, we report the
      characterization of a P. furiosus galactokinase (GALK) and its comparison with
      the P. furiosus ADP-GLK. The pyrococcal genes encoding the ADP-GLK and GALK were
      functionally expressed in Escherichia coli, and the proteins were subsequently
      purified to homogeneity. Both enzymes are specific kinases with an optimal
      activity at approx. 90 degrees C. Biochemical characterization of these enzymes
      confirmed that the ADP-GLK is unable to use ATP as the phosphoryl group donor,
      but revealed that GALK is ATP-dependent and has an extremely high affinity for
      ATP. There is a discussion about whether the unusual features of these two
      classes of kinases might reflect adaptations to a relatively low intracellular
      ATP concentration in the hyperthermophilic archaeon P. furiosus.

PMID- 11978176
TI  - Events in the immortalizing process of primary human mammary epithelial cells by
      the catalytic subunit of human telomerase.
AB  - The in vitro immortalization of primary human mammary epithelial (HME) cells
      solely by the exogenous introduction of the catalytic subunit of human telomerase
      (hTERT) has been achieved. Early passage hTERT-transfected HME (T-HME) cells
      continuously decreased the length and density of telomeres even in the presence
      of telomerase activity, with a significant number of cells staining positive for
      senescence-associated beta-galactosidase (SA-beta-gal). Subsequently, with the
      increase in cell passages, the copy number of the exogenously transfected hTERT
      gene and the percentage of SA-beta-gal positive cells were found to decrease.
      Eventually, a single copy of the exogenous hTERT gene was observed in the
      relatively later passage T-HME cells in which telomere length was elongated and
      stabilized without obvious activation of endogenous hTERT and c-Myc expression.
      In T-HME cells, the expression of two p53 regulated genes p21(WAF) and HDM2
      increased (as in primary senescent HME cells), and was found to be further
      elevated as the function of p53 was activated by treatment with DNA-damaging
      agents. p16(INK4a) was shown to be significantly higher in the primary senescent
      HME and the early passage T-HME cells when compared with the primary presenescent
      HME cells, with a dramatic repression of p16(INK4a) observed in the later passage
      T-HME cells. In addition, the expression of E2F1 and its transcription factor
      activity were found to be significantly higher in the later passage T-HME cells
      when compared with the earlier passage T-HME cells. Together, our results
      indicate that in vitro immortalization in HME cells may require the activation of
      the function of telomerase and other genetic alterations such as the spontaneous
      loss of p16(INK4a) expression.

PMID- 11978177
TI  - Nitric oxide regulates oestrogen-activated signalling pathways at multiple levels
      through cyclic GMP-dependent recruitment of insulin receptor substrate 1.
AB  - The gaseous messenger nitric oxide (NO) contributes to biological effects of
      oestrogen in target tissues, including reproductive organs, bone, cardiovascular
      and central nervous systems. Vasodilation and anti-atherosclerotic properties of
      NO have been shown to play a role in these effects. The possibility that NO acts
      also through regulation of the signal transduction cascade triggered by
      oestrogen, instead, has never been investigated. To study this we have used the
      MCF-7 human breast cancer cell line, an established model for oestrogen
      signalling. Exposure of these cells to 17-beta-oestradiol (E(2)) in the presence
      of NO gave rise to activation of signalling events additional to those triggered
      by E(2) alone, namely tyrosine phosphorylation of specific proteins, including
      the insulin receptor substrate-1, with recruitment to this adapter of the
      phosphatidylinositol 3'-kinase and persistent activation of Akt (protein kinase
      B). Active Akt, in turn, prevented E(2) from activating p42/44 extracellular
      signal-regulated kinases (ERK 1/2). These effects of NO, which were mediated
      through generation of cyclic GMP and activation of the cGMP-dependent protein
      kinase I, initiated in the first minutes after administration of oestrogen. The
      consequences, however, were long lasting, as modulation of Akt and ERK 1/2
      activities by NO was responsible for inhibition of E(2)-triggered cell growth and
      regulation of oestrogen responsive-element dependent gene transcription.
      Generation of NO is stimulated by both E(2) and growth factors known to
      contribute to the complex network of intracellular events regulating the
      biological actions of oestrogen. It is conceivable, therefore, that modulation by
      NO of E(2) early signalling, here described for the first time, has broad
      significance in regulating cellular responses to the hormone.

PMID- 11978178
TI  - Identification of the two essential groups in the family 3 beta-glucosidase from
      Flavobacterium meningosepticum by labelling and tandem mass spectrometric
      analysis.
AB  - beta-Glucosidase from Flavobacterium meningosepticum (Fbgl) catalyses the
      hydrolysis of beta-1,4-glucosidic bonds via a two-step double-displacement
      mechanism in which two amino acid residues act as nucleophile and acid/base
      catalyst. Definitive identification of these two residues is provided by the two
      active-site-directed inactivators, 2',4'-dinitrophenyl-2-deoxy-2-fluoro-beta-d
      glucoside (2FDNPG) and N-bromoacetyl-beta-d-glucosylamine (NBGN), which
      stoichiometrically label the nucleophile and the acid/base catalyst of Fbgl,
      respectively. Pseudo-first-order inactivation rate constants (k(i)) of 0.25+/
      0.01 and 0.05+/-0.01 min(-1) and dissociation constants (K(i)) of 90+/-15 and
      4.4+/-0.2 mM are determined for 2FDNPG and NBGN, respectively. Proteolytic
      digestion of the labelled proteins, followed by peptide mapping and tandem MS
      analysis identify Asp-247 and Glu-473 as the catalytic nucleophile and acid/base
      residues, respectively, of Fbgl. This study confirms that the catalytic
      nucleophile of family 3 glycohydrolase is conserved across sub-families. However,
      different sub-families may have unique general acid/base catalysts.

PMID- 11978180
TI  - A novel lactonohydrolase responsible for the detoxification of zearalenone:
      enzyme purification and gene cloning.
AB  - Zearalenone (ZEN) is converted into a far less oestrogenic product by incubation
      with Clonostachys rosea IFO 7063. An alkaline hydrolase responsible for the
      detoxification was purified to homogeneity from the fungus by a combination of
      salt precipitation and column chromatography methods. The purified enzyme was
      homodimeric with a subunit molecular mass of 30 kDa and contained an intra
      subunit disulphide bridge. On the basis of the internal peptide sequences of the
      purified protein, we cloned the entire coding region of the gene (designated as
      zhd101) by PCR techniques. The ZEN degradation activity was detected in
      heterologous hosts (Schizosaccharomyces pombe and Escherichia coli) carrying the
      cloned gene. Zhd101 could be a promising genetic resource for in planta
      detoxification of the mycotoxin in important crops.

PMID- 11978179
TI  - Interaction between the individual isoenzymes of pyruvate dehydrogenase kinase
      and the inner lipoyl-bearing domain of transacetylase component of pyruvate
      dehydrogenase complex.
AB  - Protein-protein interactions play an important role in the regulation of enzymic
      activity of pyruvate dehydrogenase kinase (PDK). It is generally believed that
      the binding of PDK to the inner lipoyl-bearing domain L2 of the transacetylase
      component E2 of pyruvate dehydrogenase complex largely determines the level of
      kinase activity. In the present study, we characterized the interaction between
      the individual isoenzymes of PDK (PDK1-PDK4) and monomeric L2 domain of human E2,
      as well as the effect of this interaction on kinase activity. It was found that
      PDK isoenzymes are markedly different with respect to their affinities for L2.
      PDK3 demonstrated a very tight binding, which persisted during isolation of PDK3
      L2 complexes using size-exclusion chromatography. Binding of PDK1 and PDK2 was
      readily reversible with the apparent dissociation constant of approx. 10 microM
      for both isoenzymes. PDK4 had a greatly reduced capacity for L2 binding (relative
      order PDK3>PDK1=PDK2>PDK4). Monomeric L2 domain alone had very little effect on
      the activities of either PDK1 or PDK2. In contrast, L2 caused a 3-fold increase
      in PDK3 activity and approx. 37% increase in PDK4 activity. These results
      strongly suggest that the interactions between the individual isoenzymes of PDK
      and L2 domain are isoenzyme-specific and might be among the major factors that
      determine the level of kinase activity of particular isoenzyme towards the
      pyruvate dehydrogenase complex.

PMID- 11978182
TI  - Are the cochrane group registers comprehensive? A case study of Japanese
      psychiatry trials.
AB  - BACKGROUND: Language bias is a form of publication bias and constitutes a serious
      threat to meta-analyses. The Cochrane Controlled Trials Register is one attempt
      to remedy this and now contains more than 300,000 citations. However we are still
      unsure if it provides comprehensive coverage, particularly for non-English
      trials. METHODS: We have recently established a comprehensive register of
      Japanese trials of psychotropic drugs through extensive personal contacts,
      electronic searches and handsearches. We examined two Cochrane psychiatry group
      registers against this Japanese database. RESULTS: The Japanese register
      contained 56 reports of randomized controlled trials (RCTs) of antidepressants
      for depression but the Cochrane Depression, Anxiety and Neurosis group register
      contained 18, with an overlap of only nine. The Japanese register contained 61
      reports of RCTs of neuroleptics for schizophrenia and the Cochrane Schizophrenia
      group register contained 36, with an overlap of only six. Taking account of some
      duplicate publications, only a quarter to a third of all relevant Japanese RCTs
      were retrievable from the Cochrane group registers. CONCLUSIONS: Similar, or
      worse, yields may be expected with RCTs conducted in other East Asian countries,
      and in other fields of medicine. What evidence there is suggests that this
      situation may lead to a systematic over estimate of treatment effect.

PMID- 11978181
TI  - Truncation of Arabidopsis thaliana and Selaginella lepidophylla trehalose-6
      phosphate synthase unlocks high catalytic activity and supports high trehalose
      levels on expression in yeast.
AB  - Plants, such as Arabidopsis thaliana and Selaginella lepidophylla, contain genes
      homologous with the trehalose-6-phosphate synthase (TPS) genes of bacteria and
      fungi. Most plants do not accumulate trehalose with the desert resurrection plant
      S. lepidophylla, being a notable exception. Overexpression of the plant genes in
      a Saccharomyces cerevisiae tps1 mutant results in very low TPS-catalytic activity
      and trehalose accumulation. We show that truncation of the plant-specific N
      terminal extension in the A. thaliana AtTPS1 and S. lepidophylla SlTPS1
      homologues results in 10-40-fold higher TPS activity and 20-40-fold higher
      trehalose accumulation on expression in yeast. These results show that the plant
      TPS enzymes possess a high-potential catalytic activity. The growth defect of the
      tps1 strain on glucose was restored, however, the proper homoeostasis of
      glycolytic flux was not restored, indicating that the plant enzymes were unable
      to substitute for the yeast enzyme in the regulation of hexokinase activity.
      Further analysis of the N-terminus led to the identification of two conserved
      residues, which after mutagenesis result in strongly enhanced trehalose
      accumulation upon expression in yeast. The plant-specific N-terminal region may
      act as an inhibitory domain allowing modulation of TPS activity.

PMID- 11978183
TI  - Publication bias in gastroenterological research - a retrospective cohort study
      based on abstracts submitted to a scientific meeting.
AB  - BACKGROUND: The aim of this study was to examine the determinants of publication
      and whether publication bias occurred in gastroenterological research. METHODS: A
      random sample of abstracts submitted to DDW, the major GI meeting (1992-1995) was
      evaluated. The publication status was determined by database searches,
      complemented by a mailed survey to abstract authors. Determinants of publication
      were examined by Cox proportional hazards model and multiple logistic regression.
      RESULTS: The sample included abstracts on 326 controlled clinical trials (CCT),
      336 other clinical research reports (OCR), and 174 basic science studies (BSS).
      392 abstracts (47%) were published as full papers. Acceptance for presentation at
      the meeting was a strong predictor of subsequent publication for all research
      types (overall, 54% vs. 34%, OR 2.3, 95% CI 1.7 to 3.1). In the multivariate
      analysis, multi-center status was found to predict publication (OR 2.8, 95% CI
      1.6-4.9). There was no significant association between direction of study results
      and subsequent publication. Studies were less likely to be published in high
      impact journals if the results were not statistically significant (OR 0.5, 95 CI
      95% 0.3-0.6). The author survey identified lack of time or interest as the main
      reason for failure to publish. CONCLUSIONS: Abstracts which were selected for
      presentation at the DDW are more likely to be followed by full publications. The
      statistical significance of the study results was not found to be a predictor of
      publication but influences the chances for high impact publication.

PMID- 11978184
TI  - Expression of p53, inducible nitric oxide synthase and vascular endothelial
      growth factor in gastric precancerous and cancerous lesions: correlation with
      clinical features.
AB  - BACKGROUND: The growth and metastasis of tumors depend on the development of an
      adequate blood supply via angiogenesis. Recent studies indicate that the
      inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF)
      and the tumor suppressor p53 are fundamental play-markers of the angiogenic
      process. Overexpression of iNOS and VEGF has been shown to induce angiogenesis in
      tumors. P53 suppresses angiogenesis by down-regulating VEGF and iNOS. The
      correlation of expression of p53, VEGF and iNOS and clinical features in gastric
      carcinogenesis, however, has not been well characterized. METHODS: The expression
      of p53, iNOS and VEGF in gastric precancerous and cancerous lesions and its
      relation with the clinical features was determined with immunohistochemistry
      (avidin-biotin-peroxidase complex method) on 55 randomly selected GC patients and
      60 symptom-free subjects from the mass survey in the high-incidence area for GC
      in Henan, northern China. RESULTS: The positive immunostaining rates for p53,
      iNOS and VEGF in gastric carcinomas were 51%, 44% and 51%, respectively, and
      correlated well with TNM stages, but did not show significant difference among
      the groups with different degrees of gastric wall invasion depth by GC. A
      positive immunostaining reaction for the iNOS protein was significantly
      correlated with lymph node metastasis (p = 0.019; Spearman correlation
      coefficient). P53 protein accumulation was higher in the poorly-differentiated
      gastric carcinoma than in well-differentiated one. In gastric biopsies, no
      positive immunostaining was observed for p53, iNOS and VEGF in the histologically
      normal tissue and chronic superficial gastritis (CSG). However, p53, iNOS and
      VEGF positive immunostaining was observed in the tissues with different
      severities of lesions of chronic atrophic gastritis (CAG), intestinal metaplasia
      (IM) and dysplasia (DYS), and the positive rates increased with the lesion
      progression from CAG to IM to DYS. A high coincidental positive and negative
      immunostaining rate for p53, iNOS and VEGF was observed both in biopsy samples
      with CAG, IM and DYS from the symptom-free subjects and in gastric cancer tissue
      from the GC patients. CONCLUSIONS: The present results indicated that p53 protein
      accumulation and increased expression of iNOS and VEGF might be responsible for
      gastric carcinogenesis and tumor aggressiveness of gastric cancer.

PMID- 11978187
TI  - Effects of stereochemical aspects on drug interaction in pharmacokinetics.
AB  - Recent literatures on enantiomer/enantiomer and enantiomer/coadministered drug
      interactions in pharmacokinetics were reviewed. The clinical significance of
      introducing the concept of stereoselectivity into pharmacokinetic interaction
      study cannot be overestimated, such as avoiding interaction-based adverse
      reactions, increasing therapeutic index, resolving the apparent anomaly in the
      plasma concentration-effect relationship and providing starting point of
      investigation into drug disposition, etc. Study in this respect should be
      enhanced.

PMID- 11978186
TI  - Variability within individuals of plasma ionic magnesium concentrations.
AB  - BACKGROUND: With the invention of the ion-selective electrode (ISE), ionic
      magnesium (iMg) is a common blood assay. This could be advantageous, as iMg is
      the biologically active form of Mg. There is some evidence that iMg has
      considerable within subject variability. RESULTS: Individual ranges averaged.08
      mmol/L (range.05 to.14). Coefficients of variation (CV) ranged from 3% to 7%
      (mean 4%) while analytical variation was determined to be 2.3%. Biological
      variability thus accounts for almost half of the variability, which is clinically
      significant, as 9 of the 13 subjects recorded at least one value below a
      reference range of.46 -.60 mmol/L. A significant within-day variation (p <.001)
      was noted, with differences between 7:00 and 10:00 as well as 10:00 and 22:00.
      Between day variations were not significant (p =.56). CONCLUSIONS: A plausible
      explanation of this data is that iMg has a circadian rhythm. Thus, cautious
      interpretation of single iMg values is warranted until future research determines
      the nature of iMg variability.

PMID- 11978185
TI  - Notch signalling is linked to epidermal cell differentiation level in basal cell
      carcinoma, psoriasis and wound healing.
AB  - BACKGROUND: Epidermal homeostasis involves the monitoring of continuous
      proliferative and differentiative processes as keratinocytes migrate from the
      basal layer to the skin surface. Recently, differentiation of epidermal stem
      cells was shown to be promoted by the Notch pathway. This pathway is
      characterised by cell-cell interactions between transmembrane proteins and was
      first implicated in lateral inhibition, patterning and cell binary choices during
      embryogenesis. METHODS: By in situ hybridisation, we investigated the in vivo
      expression of related genes, namely; Notch 1-3, Delta 1, Jagged 1, Lunatic
      Fringe, Radical Fringe and Manic Fringe during keratinocyte proliferation and
      differentiation in humans in basal cell carcinoma, psoriasis and in wound healing
      experiments, compared with normal adult skin. RESULTS: We show that the highest
      level of transcription of these genes is in the basal cell layer of non-lesional
      skin. Conversely, when keratinocytes were hyperproliferating, as in basal cell
      carcinoma, psoriasis, and during the first step of re-epithelialisation,
      expression was weak or non-existent. Furthermore, normal levels of transcripts
      were rescued in psoriatic plaques when treated by phototherapy, as well as in
      newly regenerated stratified epidermis following wound healing. CONCLUSION: The
      Notch signalling involved in the differentiation programme of normal adult human
      epidermis is altered under experimental conditions and pathologies which modify
      this programme.

PMID- 11978188
TI  - Beneficial effects of long-term administration of ONO-3144, a free radical
      scavenger, on stroke-prone SHR.
AB  - To clarify the preventive effects of ONO-3144, a free radical scavenger, on
      stroke-prone spontaneously hypertensive rats (SHRSP) and free radicals related to
      the hypertensive disorders. METHODS: Drugs with powdered chow were administered
      orally to the rats from 2- to 14-month-old. Body weight, blood pressure, rectal
      temperature, oxygen consumption rate, thyroid hormones, lipids, platelet number,
      ocular fundus, autopsy, and life span were investigated. RESULTS: ONO-3144 did
      not affect the growth, blood pressure, concentrations of thyroid hormones and
      lipids in the blood, but decreased the rectal temperature and oxygen consumption
      rate. ONO-3144 also prevented the platelet number decrease, sclerotic change of
      retinal artery, edematous and hypertrophic changes in parenchymal and circulatory
      organs. Both the average life-span and the longest life time of SHRSP given 40
      mg/kg ONO-3144 were longer than those of normotensive rats and no administration
      hypertensive rats. CONCLUSION: The oxidative f ree radicals closely relate to
      hypertension-induced pathophysiological changes in SHRSP, and ONO-3144 prevents
      the changes of those disorders, and then brings longevity.

PMID- 11978189
TI  - Trypanocidal action of 2,4-dichloro-6-phenylphenoxyethyl diethylamine
      hydrobromide (Lilly 18947) on Trypanosoma cruzi.
AB  - AIM: To study the effect of the inhibitor of cytochrome P450 known as Lilly 18947
      (2,4 dichloro-6 phenylphenoxy ethyl diethylamine) on Trypanosoma cruzi. METHODS:
      Trypanosoma cruzi epimastigotes were grown in culture, in absence or in presence
      of drug. The inhibition of its growth was followed by daily counting using a
      Neubauer chamber. The effect of Lilly 18947 on the parasite ultrastructure was
      examined by electron microscopy. To test the effect of different concentrations
      of drug on the parasite cycle, Vero cells were inoculated with trypomastigotes
      (RA strain) and after 72 h the percentage of infected cells and the number of
      intracellular parasites were estimated and expressed as the endocytic index.
      RESULTS: Growth of epimastigotes was inhibited by Lilly 18947. Concentrations as
      low a s 50 micromol/L resulted in a complete disappearance of the parasites in
      culture by the fourth day. With lower concentrations, little growth was observed
      and total (25 micro mol/L) or partial lysis (10 micromol/L) were registered by
      the eighth day of culture. Incubation of epimastigotes with 50 micromol/L of
      Lilly 18947 resulted in an early damage to cellular structures. Initial signs
      were dilatation of perinuclear membranes and mitochondria swelling. The
      infectivity of trypomastigotes to Vero cells in culture was nearly abolished at
      15 and 30 micromol/L concentrations of the drug. CONCLUSION: Lilly 18947 was able
      to harm Trypanosoma cruzi membrane functions leading to t he loss of its
      infective properties and its death.

PMID- 11978190
TI  - Expression of angiopoietin-2 and vascular endothelial growth factor in mice
      cerebral cortex after permanent focal cerebral ischemia.
AB  - AIM: To study the expressions of vascular endothelial growth factor (VEG F),
      angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tie-1, and Tie-2 in C57BL/6 mouse
      brain after permanent focal cerebral ischemia. METHODS: The mRNA levels of VEGF,
      Ang-1, Ang-2, Tie-1, and Tie-2 were measured by semiquantitative reverse
      transcription polymerase chain reaction (RT-PCR). The protein express ions of
      VEGF and Ang-2 were determined by immunohistochemistry. RESULTS: Low mRNA levels
      of VEGF, Ang-1, Ang-2, Tie-1, and Tie-2 were constitutively expressed in the
      normal cortex of mouse. After middle cerebral artery occlusion (MCAO), the
      expressions of VEGF, Ang-2, and Tie-2 mRNA were dramatically increased in the
      infarcted cortex and the elevation was remained through 7 d of ischemia. However,
      the levels of Ang-1 and Tie-1 mRNA were unchanged in the infarcted cortex.
      Immunoreactivities of Ang-2 or VEGF were hardly observed in the normal cortex.
      Ang-2 protein was evidently detected in the infarct core 8 h after MCAO and in t
      he perifocal area 1 d after MCAO. Expression of VEGF protein was elevated in the
      infarct core 2 h after MCAO and in the perifocal area 1 d after MCAO.
      Immunoreaction was restricted to endothelial cells and glial-like cells within
      the infarct core and perifocal area. CONCLUSION: The expressions of An g-2 and
      VEGF are induced after focal cerebral ischemia, which may contribute to the
      angiogenic response in the cortex of ischemic brain.

PMID- 11978191
TI  - Pentadecapeptide BPC 157 attenuates chronic amphetamine-induced behavior
      disturbances.
AB  - AIM: To investigate the effect of pentadecapeptide BPC 157 on chronic exposure to
      amphetamine in rats, particularly the changes commonly referred in chronic
      amphetamine studies as tolerance (lesser grade of stereotyped behavior, without
      increased excitability) and reverse tolerance (ie, prominent stereotyped behavior
      and heightened startle response upon late amphetamine challenges). METHODS: After
      initial application (initial single dose-regimen), amphetamine (10 mg/kg,ip) was
      given once daily till d 5 (continuous administration-regimen), and thereafter on
      d 8, 16, and 46 (intermittent administration regimen). Fo r stereotyped behavior
      and heightened startle response the observation period was 120 min after
      amphetamine application, and each animal was observed for 10 s in 5 min
      intervals. Pentadecapeptide BPC 157 (10 microg/kg or 10 ng/k g, ip) or saline
      (5.0 mL/kg, ip) were given only at the beginning of the experiment,
      simultaneously with the initial dose of amphetamine. RESULTS: In relation to
      applied initial-single/continuous/intermittent amphetamine applications regimen,
      the control amphetamine rats throughout the experiment showed the changes in
      stereotyped behavior and heightened startle response, increment or decrement,
      commonly explained in chronic amphetamine studies as tolerance and reverse
      tolerance. After t he initial application of the amphetamine, the higher BPC 157
      dosage apparently attenuated the stereotyped behavior, while the lower dosage of
      BPC 157 did not reach a statistical significance. Considering the forthcoming
      amphetamine challenges, in the rats initially treated with pentadecapeptide BPC
      157, either 10 microg- or 10 ng-dose, at the time of the first application of
      amphetamine, the stereotyped behavior remains to be attenuated after all
      additional amphetamine challenges (on d 2-5, 8, 16, and 46). This attenuation was
      not limited to stereotyped behavior only. After the initial application of the
      amphetamine the heighten ed startle response was also apparently mitigated in
      rats receiving the BPC 157 dosage, either higher or lower. Later, confronted with
      the forthcoming amphetamine challenges, they showed apparently less abnormal
      excitability at all tested points. CONCLUSION: In summary, gastric
      pentadecapeptide BPC 157 (ie, both microg- and ng-BPC 157 regimens) attenuated
      chronic amphetamine disturbances. This effect was present throughout the
      observation period at a statistically significant level. Therefore, it seems that
      this gastric pentadecapeptide BPC 157 has a modulatory effect on dopamine system,
      and it could be used in chronic amphetamine disturbances.

PMID- 11978192
TI  - Interaction of multidrug resistance reversal agents with P-glycoprotein ATPase
      activity on blood-brain barrier.
AB  - AIM: To gain further insights into the mechanism of the ATP-dependent interaction
      of P-glycoprotein (P-gp) with various multidrug resistance (MDR) reversal agents.
      METHODS: Bovine brain capillary endothelial cells (BCEC) were isolated from
      cerebral gray matter using modifications of the mechanical homogenization
      technique. Plasma membranes were prepared from BCEC. The P- gp adenosine
      triphosphatase (ATPase) activity of the isolated BCEC membranes was estimated by
      measuring inorganic phosphate liberation. RESULTS: The basal P-gp ATPase activity
      was increased by verapamil (Ver), vincristine (VCR), doxorubicin (Dox),
      tetrandrine (Tet), dauricine (DRC), berbamine (BBM), and daurisoline (DRS), with
      respective half-maximal activity concentrations Km of about 17, 5.9, 41, 2.3, 11,
      23, and 22 micromol/L. Berberine (BBR) produced a relatively slight activation.
      dl-Tetrahydropalmatine (dl-THP) and l-tetrahydropalmatine (l-THP ) does not alter
      the basal P-gp ATPase activity. Cyclosporin A (CsA) inhibited both the basal and
      the drug-stimulated ATPase activity of P-gp with high affinity. Kinetic analysis
      indicated a competitive inhibition of Ver- or VCR-stimulated ATPase activity and
      a noncompetitive inhibition of Dox- or Tet-activated ATPase activity by CsA.
      Moreover, Dox inhibited Tet-activated P-gp ATPase activity in a noncompetitive
      manner. CONCLUSION: Various MDR reversal agents could interact with P-gp and
      alter its ATPase activity in different manners. This is the result of the b road
      molecular recognition specificity of P-gp. CsA, Ver, and VCR could bin d P-gp
      either on overlapping sites or distant but interacting sites, while CsA, Dox, and
      Tet could independently bind P-gp on separated sites on blood-brain barrier.

PMID- 11978193
TI  - Interactions between quinolone antibiotics and phospholipid membrane for
      prediction of alveolar macrophage uptake in vitro.
AB  - AIM: To compare the effectiveness of the different parameters for predicting
      alveolar macrophage (AM) uptake, interactions between quinolones, including two
      amphipathic bases, and phospholipid membrane were evaluated by three different
      membrane-like systems. METHODS: AM cells were isolated, cultured as confluent
      monolayers, then incubated with drug solution at 37 degrees C. At designated time
      points, uptake was terminated by aspirating solution, followed by rinsing, cell
      lysis, a nd analysis of drug and protein concentrations. Immobilized artificial
      membrane (IAM) chromatography and liposome/buffer system were used to determine
      interactions with phospholipid membrane, expressed as lipophilicity indices, lg
      k(IAM) and lg D(L/B,7.4), respectively. An n-octano l/buffer system was also
      employed as the reference hydrophobicity, lg D(O/B,7.4)4. RESULTS: For the tested
      set, lg k(IAM) correlated more significantly with lg D(L/B,7.4) (r2 = 0.93) than
      with lgD(O/B,7.4) (r2 = 0.65). There were better correlations between either lg
      k(IAM) or lg D(L/B,7.4) and the extent of accumulation in AM than did lg DO/B,7.4
      (r2 = 0.89, 0.92, and 0.67, respectively). Correlations obtained using lg k(IAM),
      lg D(L/B,7.4), and lg D(O/B,7.4) were comparable when regressed against the
      logarithm of influx rate into AM f or a set consisting of five amphoteric
      quinolones and quinidine. CONCLUSION: Liposome/buffer system and IAM
      chromatography could provide nearly similar scale of lipophilicity measurement,
      both distinct from n-octanol/buffer system. Accumulation by AM was better
      described by lg k(IAM) or lg D(L/B,7.4) than lg D(O/B,7.4), and the passive
      diffusion was principal form during drugs transported across AM membrane.

PMID- 11978195
TI  - Effect of rhynchophylline on apoptosis induced by dopamine in NT2 cells.
AB  - AIM: To study the effect of rhynchophylline (Rhy) on the apoptosis induced by
      dopamine (DA) in NT2 cell line. METHODS: Release of lactate dehydrogenase (LDH)
      from cultured cells was determined by enzyme-linked immunosorbant assay;
      apoptotic NT2 neurons by terminal de oxynucleotidyl transferase(TdT)-mediated
      dUTP nick end labeling method; DNA fragmentation by agarose gel electrophoresis;
      Bcl-2 protein expression by Western blotting. RESULTS: DA 100 - 500 micromol/L
      increased release of LDH, number of apoptotic NT 2 neurons, and DNA fragmentation
      (P < 0.01). NT2 cells survival rate was decreased. Rhy 5 and 50 micromol/L
      reduced the percentage of apoptosis after treated with DA 100 micromol/L for 6 h
      in both with and without bcl-2 gene neurons (P < 0.05, P < 0.01, respectively).
      The expression of Bcl-2 protein was not affected by Rhy. CONCLUSION: Rhy
      protected NT2 neurons from the damage induced by DA.

PMID- 11978194
TI  - Anti-inflammatory effect of recombinant human superoxide dismutase in rats and
      mice and its mechanism.
AB  - AIM: To investigate the anti-inflammatory effects and mechanism of recombinant
      human superoxide dismutase (rhSOD). METHODS: Inflammation models such as croton
      oil-induced ear swelling and carrageenan-induced hind paw edema in mice and rats
      were prepared. The nitric oxide synthase (NOS ) activity was measured by NADPH
      diaphoras stain assay, N-acetyl-beta-D-glucosaminidase (beta-NAG) activity by
      spectrophotography, malondialdehyde (MDA) content by thiobarbituric acid (TBA)
      fluorescence technique, and interleukin-1beta (IL -1beta), tumor necrosis factor
      alpha (TNF alpha), and IL-8 content by radioimmunoassay (RIA). RESULTS: rhSOD 20
      80 mg/kg ip, 40-80 mg/kg im, and 80 mg/kg ip significantly inhibited carrageenan
      induced paw edema in rats, croton oil-induced ear swelling in mice, and
      carrageenan-induced hind paw edema in mice, respectively. In the rat arthritis
      induced by carrageenan, rhSOD 40 mg/kg reduced MDA content in inflamed paws,
      inhibited NOS activity, and lowered the content of IL-1beta and TNFalpha in
      exudate significantly. The inhibitory effect of rhSOD 40 mg/kg ip on IL-1beta
      production was more evident than that of dexamethasone 2 mg/kg ip. Also rhSOD
      obviously inhibited neutrophil infiltration; However, rhSOD had no effect on beta
      NAG activity in exudate. CONCLUSION: rhSOD has anti-inflammatory effect on
      experimental inflammation in rats and mice, and its mechanisms are relevant to
      oxygen free radical scavenging, anti-lipid peroxidation, inhibition of neutrophil
      infiltration, and formation of inflammatory cytokines.

PMID- 11978196
TI  - Cloning and characterization of a novel isoform of calpastatin in human adult
      testis.
AB  - AIM: To clone a new gene related to human spermatogenesis. METHODS: cDNA probes
      of embryo and adult testis were used to hybridize the cDNA microarray of adult
      testis, and the clones of differential hybridization were sequenced and analyzed.
      RESULTS: A novel isoform of calpastatin exclusively and highly expressed in human
      adult testis was found. CONCLUSION: A novel isoform of calpastatin expresses in
      human testis and it is related to spermatogenesis.

PMID- 11978197
TI  - Metabolism of roxithromycin in phenobarbital-treated rat liver microsomes.
AB  - AIM: To investigate the metabolism of roxithromycin (RXM) in rat liver microsomes
      and the possible effects of RXM and its metabolites on cytochrome P-450 (CYP450).
      METHODS: Liver microsomes of Wistar rats, induced by phenobarbital, were prepared
      using ultracentrifuge method. RXM in vitro metabolism was stu died with the
      microsome incubation. The metabolites were separated and assayed by li quid
      chromatography-tandem mass spectrometry (LC-MSn), and were further identified by
      comparison of their mass spectra and LC behavior to synthesized references.
      RESULTS: N-Mono- and N-di-demethyl metabolites a s well as O-dealkylated
      metabolite (erythromycin oxime) were detected in microsomal incubates. RXM and
      its metabolites expressed weak potency to form inactive complexes with CYP450.
      CONCLUSION: N-Demethylation and oxime ether side chain O- dealkylation are main
      biotransformation pathways of RXM in phenobarbital-treated rat liver microsomes.
      Both routes were found to be NADPH-dependent. RXM and its metabolites showed weak
      inhibitory effects on CYP450.

PMID- 11978198
TI  - Caspases promoted DADAG-induced apoptosis in human leukemia HL-60 cells.
AB  - AIM: To investigate the roles of caspases in diacetyldianhydrogalactitol (DADAG)
      induced apoptosis in human leukemia HL-60 cells. METHODS: Inhibition of
      proliferation was measured by MTT assay. DADAG-induced apoptosis in HL-60 cells
      was observed by electron microscopy, flow cytometry, and DNA fragmentation assay.
      Caspase-3 activity was determined by ApoAlert CPP32 colorimetric assay kit. The
      cleavage of substrates of caspases was detected by Western blot. RESULTS: DADAG
      exhibited potent antiproliferative activity and induced apoptosis in HL-60 cells.
      After treatment with DADAG 8 mg/L for 24 h, caspase-3 activity increased markedly
      and the cleavage of poly-(ADP-ribose) polymerase (PARP), lamin B, and DFF45
      appeared. All of the apoptotic signals were suppressed by z-VAD fmk (a general
      inhibitor of caspase activities), whereas z-DEVD fmk, a selective inhibitor of
      caspase-3 activity, only induced partial reversion of the apoptotic effects.
      CONCLUSION: DADAG induced apoptosis in HL-60 cells by activating caspases.
      Caspases promoted apoptosis through the cleavage of substrates of PARP, lamin B,
      and DFF45.

PMID- 11978199
TI  - Hypoglycemic efficacy of pulmonary delivered insulin dry powder aerosol in rats.
AB  - AIM: To observe the hypoglycemic efficacy of pulmonary delivery of insulin in dry
      powder aerosol form. METHODS: Insulin dry powder, made of insulin and other
      proper materials, was insufflated in rat lung from an incision in the throat.
      Meanwhile, insulin injection was administered to other rats. Glucose
      concentration in blood was determined in the following 7 h. The areas above the
      curve (AAC) of glucose concentration in blood were used to evaluate the efficacy.
      RESULTS: The percent minimum blood glucose levels, compared with the glucose
      levels before the administration, for pulmonary deliver ed insulin at the doses
      of 20, 10, 5, and 2.5 U/kg were 6.5 %, 16.6 %, 24.6 %, and 57.0 %, respectively.
      The AAC of insulin 5 U/kg by pulmonary delivery was very close to that of
      subcutaneous administration at the same dose. There was a linear relationship
      between AAC and the logarithmic dose of pulmonary delivered insulin. CONCLUSION:
      The pulmonary delivery of insulin acts effectively and rapidly.

PMID- 11978200
TI  - In vitro metabolic characteristics of cytochrome P-450 2A6 in Chinese liver
      microsomes.
AB  - AIM: To investigate the metabolic characteristics of cytochrome P-450 C YP2A6 in
      human liver microsomes. METHODS: Cytochrome P-450 enzyme activities were measured
      by biochemical assays. Xenobiotics were employed to observe their effects on
      CYP2A6 in vitro. The kinetics of coumarin 7-hydroxylase was determined, and the
      correlation between CYP2A6 and UDP-glucuronosyltransferase (UGT) was analyzed.
      RESULTS: CYP2A6 activities of human liver microsomes were from 0.47 to 4.14
      micromol . min-1 . g-1, with a 8.8-fold variation. The Km and Vmax of CYP2A6
      ranged from 0.25 to 1.56 micromol/L and 1.41 to 8.70 micromol . min-1 . g-1,
      respectively. CYP2A6 activity was markedly inhibited (> 50 %) by pilocarpine,
      diethyldithio carbamic (DDC), and rifampicin, the IC50 was 5.31 micromol/L,
      156.35 micromol/L, and 38.81 micromol/L, respectively. alpha-Naphthoflavone,
      sulfaphenazole, troleandomycin (TAO), ketoconazole, phenobarbital, prednisolone,
      and azithromycin had little or no effects on coumarin 7-hydroxylation. A
      significant correlation was observed between CYP2A6 and UGT2 (r = 0.9453, P <
      0.05). CONCLUSION: CYP2A6 activity and kinetics exhibited a considerable
      variation in human liver microsomes in vitro, and a significant correlation was
      existed between CYP2A6 and phase II enzyme UGT2. Not only pilocarpine, CYP2A6
      specific inhibitor, but also rifampicin and DDC inhibited CYP2A6 activity
      selectively.

PMID- 11978202
TI  - Can high-dose supplementation with vitamins C and E, beta carotene, and zinc slow
      the progression of macular degeneration?

PMID- 11978201
TI  - Effects of scopolamine and physostigmine on acquisition of morphine-treated rats
      in Morris water maze performance.
AB  - AIM: To investigate effects of morphine on acquisition process of rats a nd
      interactions of opioid and cholinergic systems by Morris water maze performance.
      METHODS: Morris water maze was used to measure the latency of rats with drug s
      treatment to find the covert platform. RESULTS: Chronic morphine administration
      (10 mg/kg) impaired the acquisition process of rats in Morris water maze task.
      Appreciable difference was identified with morphine 10 mg/k g group compared with
      morphine 3 mg/kg group. Co-administration of morphine (10 mg/kg) and scopolamine
      (3 mg/kg) aggravated acquisition impairment induced by morphine 1 0 mg/kg or
      scopolamine alone, though scopolamine itself induced no salient changes in
      acquisition capabilities of rats. In addition, physostigmine (0.1 mg/kg) could
      appreciably attenuate morphine-induced acquisition impairment. CONCLUSION:
      Morphine 10 mg/kg evidently impaired acquisition process of rats. There was a
      close relationship between the acquisition capabilities of morphine-treated rats
      and the functions of cholinergic system.

PMID- 11978203
TI  - Are progesterone or progestogens effective in managing premenstrual syndrome
      (PMS) symptoms?

PMID- 11978204
TI  - Can patients hospitalized with community-acquired pneumonia be treated safely and
      effectively with oral antibiotics?

PMID- 11978205
TI  - Does long-term erythromycin treatment reduce the number of common cold infections
      and subsequent exacerbations in patients with chronic obstructive pulmonary
      disease (COPD)?

PMID- 11978206
TI  - Clinical inquiries. Is prostate-specific antigen (PSA) screening indicated for
      any subgroup of men?

PMID- 11978207
TI  - Clinical inquiries. What is the best treatment for impacted cerumen?

PMID- 11978208
TI  - Clinical inquiries. What is the most effective treatment for acute low back pain?

PMID- 11978209
TI  - Treatment of postherpetic neuralgia: a systematic review of the literature.
AB  - OBJECTIVES: We wanted to determine whether any treatment had been shown to reduce
      pain or disability from postherpetic neuralgia (PHN), a common sequela of herpes
      zoster in elderly patients. STUDY DESIGN: We undertook a systematic review of
      English-language randomized controlled trials (RCTs) of treatments of PHN with
      evaluation periods longer than 24 hours. DATA SOURCES: We systematically searched
      MEDLINE, Current Contents, and the Cochrane Library. We also searched reference
      lists of identified trials and reviews and contacted content experts. OUTCOMES
      MEASURED: Two reviewers independently evaluated RCTs for methodologic quality and
      data extraction. Outcomes of primary focus were pain and quality of life.
      RESULTS: Twenty-seven RCTs met inclusion criteria and were reviewed. Six trials
      of tricyclic antidepressants found evidence for clinically meaningful effects
      over 6 weeks. All other treatments were evaluated in no more than 2 trials
      meeting our inclusion criteria. Topical capsaicin 0.075%, gabapentin, and
      controlled-release oxycodone were shown to be effective, but the clinically
      meaningful benefit is difficult to quantify. Intrathecal methylprednisolone and
      possibly bupivacaine sympathetic blocks are helpful in refractory cases. Other
      treatments evaluated, including topical lidocaine, had no evidence or
      inconsistent evidence of benefit. CONCLUSIONS: No single best treatment for PHN
      is known. Tricyclic antidepressants, topical capsaicin, gabapentin, and oxycodone
      are effective for alleviating PHN; however, long-term, clinically meaningful
      benefits are uncertain and side effects are common. Patients with PHN refractory
      to these therapies may benefit from intrathecal methylprednisolone. Little
      evidence is available regarding treatment of PHN of less than 6 months' duration.

PMID- 11978210
TI  - Do all hospitals need cesarean delivery capability? An outcomes study of
      maternity care in a rural hospital without on-site cesarean capability.
AB  - OBJECTIVES: We analyzed perinatal outcomes at a rural hospital without cesarean
      delivery capability. STUDY DESIGN: This was a historical cohort outcomes study.
      POPULATION: The study population included all pregnant women at 20 weeks or
      greater of gestational age (n = 1132) over a 5-year period in a predominantly
      Native American region of northwestern New Mexico. OUTCOMES MEASURED: The
      outcomes studied included perinatal mortality, neonatal morbidity, obstetric
      emergencies, intrapartum and antepartum transfers, and cesarean delivery rate. We
      did a detailed case review of all obstetric emergencies and low-Apgar-score
      births at Zuni-Ramah Hospital and all cesarean deliveries for fetal distress at
      referral hospitals. RESULTS: Of the 1132 women in the study population, 64.7% (n
      = 735) were able to give birth at the hospital without operative facilities;
      25.6% (n = 290) were transferred before labor; and 9.5% (n = 107) were
      transferred during labor. The perinatal mortality rate of 11.4 per 1000 (95%
      confidence interval, 5.1-17.8) was similar to the nationwide rate of 12.8 per
      1000 even though Zuni-Ramah has a high-risk obstetric population. No instances of
      major neonatal or maternal morbidity caused by lack of surgical facilities
      occurred. The cesarean delivery rate of 7.3% was significantly lower than the
      nationwide rate of 20.7% (P &lt.001). The incidence of neonates with low Apgar
      scores (0.54%) was significantly lower than the nationwide rate (1.4%). The
      incidence of neonates requiring resuscitation (3.4%) was comparable to the
      nationwide rate (2.9%). CONCLUSIONS: The presence of a rural maternity care unit
      without surgical facilities can safely allow a high proportion of women to give
      birth closer to their communities. This study demonstrated a low level of
      perinatal risk. Most transfers were made for induction or augmentation of labor.
      Rural hospitals that do not have cesarean delivery capability but are part of an
      integrated perinatal system can safely offer obstetric services by using
      appropriate antepartum and intrapartum screening criteria for obstetric risk.

PMID- 11978211
TI  - Diagnosis and 10-year follow-up of a community-based hepatitis C cohort.
AB  - OBJECTIVE: To determine the health care follow-up and treatment associated with
      physician-diagnosed hepatitis C (HCV) in a community-based population. STUDY
      DESIGN: We conducted a retrospective medical record review using records from all
      providers in Olmsted County, Minnesota. POPULATION: The study incorporated all
      Olmsted County residents with physician-diagnosed hepatitis C from 1990 through
      1999. OUTCOMES MEASURED: We assessed demographic and health status information as
      well as health services use in subjects with physician-diagnosed HCV. RESULTS:
      Physicians diagnosed hepatitis C in 355 subjects (219 men [62%], 136 women
      [38%]), mean age 43 years, in the 10-year period studied. About half of diagnoses
      (45%, n = 159) were confirmed with polymerase chain reaction or liver biopsies.
      Identified risk factors included IV drug use (50%), multiple sex partners (36%),
      and blood transfusion (30%). Follow-up assessment with aspartate
      aminotransferase/amino alanine transferase (AST/ALT) tests occurred in about half
      (49%) of subjects, while 202 subjects (60%) were referred for gastrointestinal
      (GI) specialist evaluation and 49 patients (14% of all, 25% of those referred to
      a GI specialist) had specific treatment for hepatitis C. Although well over half
      of patients (60%) had possible contraindications to HCV treatment, including
      heavy alcohol use, few were referred for chemical dependency therapy.
      CONCLUSIONS: In this community, follow-up and treatment related to HCV were
      limited. Attention to prevention of disease-accelerating co- infections was only
      modest. Referral or documented recommendations for treatment of alcoholism or
      heavy chronic alcohol ingestion were minimal.

PMID- 11978212
TI  - Perceptions and needs of patients with migraine: a focus group study.
AB  - OBJECTIVE: This study's purpose was to identify the areas that people find most
      difficult in living with migraines and, in that regard, what kinds of assistance
      would be most helpful to them and to other people who have migraine headaches.
      STUDY DESIGN: Four focus groups, each consisting of 4 to 8 participants, were
      held. Discussions, which were recorded and organized according to category and
      theme, focused on problems in living with migraines and effective treatment of
      migraines. POPULATION: Participants were 24 people who had been experiencing 1 to
      2 migraines a month, each lasting 1 to 2 days, for at least 6 months. RESULTS:
      Five themes emerged: (1) impact on family, (2) misunderstanding by others, (3)
      effect on work, (4) physician care issues, and (5) issues related to medical
      insurance and drug companies. A majority of participants identified early
      treatment as the most important consideration for new migraine sufferers. Many
      participants preferred to have a relationship with their physicians in which they
      developed a treatment plan together rather than receiving generic educational
      materials. CONCLUSIONS: Results suggest that patients are interested in
      understanding their migraines and securing relevant information in addition to
      obtaining pain relief. Patients desired collaborative relationships with their
      physicians and a team approach to treatment. Suggestions for physicians who treat
      patients who have migraines are reviewed.

PMID- 11978213
TI  - Defining effective clinician roles in end-of-life care.
AB  - OBJECTIVE: Our goal was to determine primary care clinician perceptions of what
      is important to the provision of quality end-of-life care. STUDY DESIGN: We used
      ethnography, a qualitative research method involving the use of open-ended
      semistructured interviews. POPULATION: We included 38 family practice residency
      faculty from 9 community residency programs of the Affiliated Family Practice
      Residency Network, Department of Family Medicine, University of Washington School
      of Medicine. OUTCOMES MEASURED: The roles described by interviewees when
      discussing their best practices while delivering end-of-life care were compiled.
      RESULTS: Primary care clinicians organize their delivery of quality end-of-life
      care predominantly through their relationships with patients and families. They
      play 3 roles when providing end-of-life care. As consultants, clinicians provide
      expert medical advice and treatment. As collaborators, they seek to understand
      the patient and family experience. Seasoned clinicians act as guides, using their
      personal intuitive knowledge of patient and family to facilitate everyone's
      growth when providing end-of-life care. CONCLUSIONS: Shifting clinician focus
      from skills and knowledge toward relationship, meaning, and roles provides new
      opportunities to improve end-of-life care for patients, families, and clinicians.

PMID- 11978214
TI  - Evaluation and treatment of the adult patient with migraine.

PMID- 11978215
TI  - Experience, expertise, or specialty? Uses and misuses of a reference.
AB  - OBJECTIVE: To analyze systematically the manner in which the results of a
      published study are presented in subsequent publications that refer to it. STUDY
      DESIGN: We identified a convenience sample of 121 scientific papers that referred
      to an often-cited 1996 study by Kitahata and colleagues. This study reported that
      greater primary care physician experience with AIDS was associated with lower
      mortality among their patients with AIDS. OUTCOMES MEASURED: We determined the
      manner in which the results of the Kitahata and coworkers study were presented,
      the type of article, and whether its focus was on HIV care. RESULTS: Most of the
      articles reviewed (78%) appropriately referred to the study as evidence of
      improved outcomes with increasing provider experience. However, 8% of the
      articles reviewed referred to the study as evidence of improved outcomes with
      specialty care and 3% referred to it as evidence of the benefits of expert care.
      Articles that referred to the study as evidence of improved outcomes with
      specialty care were more likely to be review articles and articles with a non-HIV
      focus. CONCLUSIONS: This study demonstrates that misrepresentation of the
      findings of published studies is not uncommon. More needs to be done to ensure
      the accuracy of references in scientific publications.

PMID- 11978216
TI  - What do we know about socioeconomic status and congestive heart failure? A review
      of the literature.
AB  - OBJECTIVE: To examine and assess the available literature concerning the effects
      of socioeconomic status (SES) and congestive heart failure (CHF). STUDY DESIGN:
      We examined electronic databases, including: MEDLINE, EMBASE, Social Science
      Citation Index, Science citation index, the Cochrane Database, and Bandolier. We
      hand searched recent copies of appropriate journals and scrutinized lists of
      identified papers. The search terms we used included "heart failure," "cardiac
      failure," "ventricular dysfunction," "social class," "socioeconomic," "poverty,"
      and "deprivation." Two reviewers independently examined and selected papers for
      inclusion. A standardized data collection form was used for data extraction.
      OUTCOMES MEASURED: We measured (1) prevalence; (2) differences in care (eg, use
      of diagnostic tests); (3) morbidity (eg, health care use); and (4) mortality.
      DATA SOURCES: We examined all English-language abstracts or papers concerning
      human research related to the subject of SES and CHF, including all clinical
      trials, reviews, discussion papers, and editorials. RESULTS: Only 8 clinical
      studies were identified that specifically examined aspects of the relationship
      between socioeconomic status and CHF. Key themes included increased
      hospitalization rates with increasing social deprivation; lower income inversely
      associated with being placed on a waiting list for transplantation; and that
      those of lower socioeconomic status had a greater severity of illness on
      admission. CONCLUSIONS: There is a paucity of generalizable high-quality research
      in this subject area. Crucial issues not addressed include the effects, if any,
      of socioeconomic status on the behaviors of health care providers. Further
      investigation, with a more holistic approach, is necessary to inform future
      intervention strategies aimed at reducing excess mortality from CHF.

PMID- 11978217
TI  - Should patients with acute cough or bronchitis be treated with beta-2 agonists?

PMID- 11978218
TI  - Does long-term bupropion (Zyban) use prevent smoking relapse after initial
      success at quitting smoking?

PMID- 11978219
TI  - Can a simple warfarin initiation scheme predict the maintenance dose in patients
      with nonrheumatic atrial fibrillation?

PMID- 11978220
TI  - Which oral triptans are effective for the treatment of acute migraine?

PMID- 11978222
TI  - Advising patients to stop smoking.

PMID- 11978223
TI  - Which database for which search?

PMID- 11978224
TI  - In patients with diabetes and hypertension, should treatment start with an ACE
      inhibitor instead of a diuretic or beta blocker?

PMID- 11978225
TI  - Does cerclage prevent preterm birth or decrease perinatal morbidity when
      performed on the identification of a short cervix by second-trimester ultrasound?

PMID- 11978226
TI  - Which is better for the management of postpartum perineal pain: Ibuprofen or
      acetaminophen with codeine?

PMID- 11978227
TI  - Should antioxidants be added to simvastatin and niacin for patients with coronary
      disease?

PMID- 11978228
TI  - Clinical inquiries. How effective are exercise and physical therapy for chronic
      low back pain?

PMID- 11978229
TI  - Clinical inquiries. How often is coughing the presenting complaint in patients
      with gastroesophageal reflux disease?

PMID- 11978230
TI  - Clinical inquiries. What is the differential diagnosis of chronic diarrhea in
      immunocompetent patients?

PMID- 11978231
TI  - Family physicians' referral decisions: results from the ASPN referral study.
AB  - OBJECTIVE: To examine family physicians' referral decisions, which we
      conceptualized as having 2 phases: whether to refer followed by to whom to refer.
      STUDY DESIGN: Prospective cohort study. POPULATION: All visits (N = 34,519) and
      new referrals (N = 2534) occurring during 15 consecutive business days in the
      offices of 141 family physicians in 87 practices located in 31 states. OUTCOMES
      MEASURED: Rates of referral, reasons for referral, practitioners referred to,
      health problems prompting referral, and reasons for selecting particular
      specialists. RESULTS: Approximately 1 in 20 (5.1%) office visits led to referral.
      Although 68% of referrals were made by physicians during office visits, 18% were
      made by physicians during telephone conversations with patients, 11% by office
      staff with input from the physician, and 3% by staff without physician input.
      Physicians endorsed a mean of 1.8 reasons for making a referral. They sought
      specialists' advice on either diagnosis or treatment for 52.1% of referrals and
      asked the specialist to direct medical management for 25.9% and surgical
      management for 37.8%. Patient request was one reason for 13.6% of referrals.
      Fifty conditions accounted for 76% of all referrals. Surgical specialists were
      sent the largest share of referrals (45.4%), followed by medical specialists
      (31.0%), nonphysician clinicians (12.1%), obstetrician-gynecologists (4.6%),
      mental health professionals (4.2%), other practitioners (2.0%), and generalists
      (0.8%). Physicians recommended a specific practitioner to the patient for most
      (86.2%) referrals. Personal knowledge of the specialist was the most important
      reason for selecting a specific specialist. CONCLUSIONS: Referrals are commonly
      made during encounters other than office visits, such as telephone conversations
      or staff-patient interactions, in primary care practice. Training in the referral
      process should ensure that family physicians obtain the skills necessary to
      expand their scope of practice, when appropriate; determine when and why a
      patient should be referred; and identify the type of practitioner to whom the
      patient should be sent.

PMID- 11978232
TI  - Does career dissatisfaction affect the ability of family physicians to deliver
      high-quality patient care?
AB  - OBJECTIVES: A usual source of care is associated with better health outcomes.
      Dissatisfaction among family physicians and general practitioners (FP/GPs) may
      compromise the accessibility of a usual source of care and the quality of
      services. We examined the association between FP/GP dissatisfaction and an
      inability to deliver high-quality care. STUDY DESIGN: We performed a secondary
      data analysis of the Community Tracking Study (CTS) Physician Survey (1996-1997).
      POPULATION: The study included a nationally representative sample of more than
      12,000 nonfederal physicians practicing direct patient care in the United States.
      OUTCOMES MEASURED: We measured associations of career dissatisfaction with
      physicians&amprsquo perceptions of their ability to provide high-quality care as
      defined by 6 survey items. Multivariate analyses controlled for the effects of
      personal, professional, and practice characteristics. RESULTS: Among FP/GPs in
      1996-1997, more than 17% were dissatisfied. Age was the most significant personal
      factor associated with dissatisfaction; 25.1% of those aged 55 to 64 years
      reported dissatisfaction compared with only 10.1% of those younger than 35 years.
      Other personal or professional characteristics significantly associated with
      FP/GP dissatisfaction included osteopathic training, graduation from a foreign
      medical school, full practice ownership, and an income of less than $100,000.
      Physicians dissatisfied with their careers were much more likely to report
      difficulties in caring for patients, strongly disagreeing (vs strongly agreeing,
      odds ratio [OR] 1.0) that they had enough clinical freedom (OR 7.89; 95%
      confidence interval [CI], 4.86-12.83); continuous patient relationships (OR 7.11;
      95% CI, 4.90-10.33); no financial penalties for clinical decisions (OR 4.44; 95%
      CI, 3.13-6.31); adequate time with patients (OR 4.42; 95% CI, 2.84-6.87); ability
      to provide quality care (OR 4.26; 95% CI, 2.88-6.31); and sufficient
      communication with specialists (OR 3.57; CI, 2.20-5.80). CONCLUSIONS: An
      inability to care for patients is significantly associated with career
      dissatisfaction. This relationship has implications for the achievement of policy
      objectives related to access, having a usual source of care, and quality.

PMID- 11978233
TI  - The relationship between insomnia and health-related quality of life in patients
      with chronic illness.
AB  - OBJECTIVES: To determine the association between insomnia and health-related
      quality of life (HRQOL) in patients with chronic illness after accounting for the
      effects of depression, anxiety, and medical comorbidities. STUDY DESIGN: We used
      a cross-sectional analysis of Medical Outcomes Study (MOS) data. POPULATION: The
      sample consisted of 3445 patients who completed a self-administered questionnaire
      and who were given a diagnosis of 1 or more of 5 chronic medical and psychiatric
      conditions by an MOS clinician. Patients were recruited from the offices of
      clinicians practicing family medicine, internal medicine, endocrinology,
      cardiology, and psychiatry in 3 US cities. OUTCOMES MEASURED: Outcomes were sleep
      items, health-related quality of life as measured by the Medical Outcomes Study
      Short Form Health Survey (SF-36), chronic medical comorbidity, depression, and
      anxiety. Insomnia was defined as the complaint of difficulty initiating or
      maintaining sleep. RESULTS: Insomnia was severe in 16% and mild in 34% of study
      patients. Patients with insomnia demonstrated significant global decrements in
      HRQOL. Differences between patients with mild insomnia versus no insomnia showed
      small to medium decrements across SF-36 subscales ranging from 4.1 to 9.3 points
      (on a scale of 0 to 100); the corresponding decrements for severe insomnia
      (versus no insomnia) ranged from 12.0 to 23.9 points. CONCLUSIONS: Insomnia is
      independently associated with worsened HRQOL to almost the same extent as chronic
      conditions such as congestive heart failure and clinical depression.

PMID- 11978234
TI  - Does the patient's sex influence cardiovascular outcome after acute myocardial
      infarction?
AB  - OBJECTIVES: To determine whether outcome differences based on the patient's sex
      occur after myocardial infarction (MI) at a large private hospital. STUDY DESIGN:
      We conducted a large cohort study. POPULATION: Inclusion required hospital
      admission between January 1, 1998, and June 30, 1999, and a diagnosis of acute MI
      or subendocardial infarction. The number of patients included in the study was
      1669. Data were collected at discharge on age, sex, race, health insurance,
      hypercholesterolemia, diabetes, smoking, hypertension, and the extent of coronary
      artery disease. OUTCOMES MEASURED: The 8 outcomes analyzed were angiogram,
      angioplasty, stent placement, coronary artery bypass grafting (CABG), mortality,
      time in the intensive care unit, total length of stay, and combined
      catheterization procedures. RESULTS: After adjusting for 7 confounding variables,
      we found no significant differences between men and women for mortality, ICU
      time, total hospital time, stent placement, angiogram, angioplasty, or combined
      catheterization procedures. Men had significantly more CABG (relative risk [RR]
      1.96, P <.01). Among patients who underwent CABG (N = 204), men had significantly
      more 3-vessel coronary disease (RR 1.44, P <.01) and left main coronary artery
      disease greater than 50% (RR 1.58, P <.01). Once we had controlled for the extent
      of coronary artery disease, we found no difference between the sexes for CABG.
      CONCLUSIONS: During hospitalization after an MI, most cardiovascular outcomes and
      process measures are the same for men and women. The greater frequency of CABG in
      men than in women is explained by men's greater frequency of 3-vessel and
      advanced left-main coronary disease.

PMID- 11978236
TI  - What do family physicians think about spirituality in clinical practice?
AB  - OBJECTIVES: To describe the context in which physicians address patients'
      spiritual concerns, including their attitudes toward this task, cues to
      discussion, practice patterns, and barriers and facilitators. STUDY DESIGN: This
      was a qualitative study using semistructured interviews of 13 family physicians.
      POPULATION: We selected board-certified Missouri family physicians in a nonrandom
      fashion to represent a range of demographic factors (age, sex, religious
      background), practice types (academic/community practice; urban/rural), and
      opinions and practice regarding physicians' roles in addressing patients'
      spiritual issues. OUTCOMES MEASURED: We coded and evaluated transcribed
      interviews for themes. RESULTS: Physicians who reported regularly addressing
      spiritual issues do so because of the primacy of spirituality in their lives and
      because of the scientific evidence associating spirituality with health.
      Respondents noted that patients' spiritual questions arise from their unique
      responses to chronic illness, terminal illness, and life stressors. Physicians
      reported varying approaches to spiritual assessment; affirmed that spiritual
      discussions should be approached with sensitivity and integrity; and reported
      physician, patient, mutual physician-patient, and situational barriers.
      Facilitators of spiritual discussions included physicians' modeling a life that
      includes a spiritual focus. CONCLUSIONS: These physicians differ in their comfort
      and practice of addressing spiritual issues with patients but affirm a role for
      family physicians in responding to patients' spiritual concerns. Factors that
      form a context for discussions of spiritual issues with patients include
      perceived barriers, physicians' role definition, familiarity with factors likely
      to prompt spiritual questions, and recognition of principles guiding spiritual
      discussions.

PMID- 11978235
TI  - How do primary care physicians use long-term acid suppressant drugs? A population
      based analysis of Dutch general practices.
AB  - OBJECTIVES: A considerable proportion of the medication budget of Dutch general
      practitioners is spent on prescribed long-term acid suppressant drugs. We
      investigated the magnitude of long-term prescription of acid suppressant drugs in
      general practice and the frequency and means of confirming the primary working
      diagnosis. STUDY DESIGN: We used a retrospective descriptive study of 24 general
      practices in the Amsterdam region. POPULATION: We identified those receiving long
      term acid suppressant therapy (12 or more weeks/year) from a total of 46,813
      patients by extracting data from pharmacy databases. OUTCOMES MEASURED: We
      measured the amount and duration of prescriptions for each medication,
      indications for prescription, and investigations performed by general
      practitioners. RESULTS: Of the 46,813 patients, 922 (2%) received long-term acid
      suppressant therapy. The duration of prescription varied from 12 weeks in 8% of
      patients to &gt 52 weeks in 23% of patients (mean = 33 weeks). In 25% of
      patients, no investigations were performed; 75% of patients underwent endoscopy
      or ingested a barium meal. The predominant diagnoses in investigated patients
      were ulcer disease (39%), gastroesophageal reflux disease (49%), and functional
      dyspepsia (gastritis, normal aspect; 18%). Helicobacter pylori status was
      available in 29% of patients with ulcer disease. Eradication therapy was reported
      in 44% of these patients. CONCLUSIONS: Among patients of physicians in general
      practice in the Amsterdam region, 2% used long-term acid suppressants. Patients
      with ulcer disease may stop taking acid suppressants after apparent successful H
      pylori eradication. Tapering strategies must be developed for patients with mild
      reflux disease or functional dyspepsia.

PMID- 11978237
TI  - Challenges posed by a scientific approach to spiritual issues.

PMID- 11978238
TI  - The Wisconsin Upper Respiratory Symptom Survey (WURSS): a new research instrument
      for assessing the common cold.
AB  - OBJECTIVE: To develop a sensitive, reliable, responsive, easy-to-use instrument
      for assessing the severity and functional impact of the common cold. STUDY
      DESIGN: We created an illness-specific health-related quality-of-life outcomes
      instrument. This original questionnaire was used in a 1999 randomized trial of
      echinacea for the common cold. In 2000 we used cognitive interview and focus
      group qualitative methods to further develop the instrument. Semistructured
      interviews used open-ended questions to elicit symptoms, terminology, and
      perceived functional impact. Responses were used to improve the instrument.
      POPULATION: The randomized trial watched 142 University of Wisconsin students for
      a total of 953 days of illness. The subsequent qualitative instrument development
      project recruited 74 adults with self-diagnosed colds for 56 in-person interviews
      and 3 focus groups. OUTCOMES MEASURED: We measured specific symptoms, symptom
      clusters (dimensions), functional impact, and global severity. RESULTS: The
      original questionnaire included 20 questions: a global severity indicator, 15
      symptom-severity items using 9-point severity scales, and 4 yes/no functional
      assessments. Data from the trial provided evidence of 4 underlying dimensions:
      nasal, throat, cough, and fever and aches, with reliability coefficients of
      0.663, 0.668, 0.794, and 0.753, respectively. Qualitative assessments from the
      interviews and focus groups led us to expand from 15 to 32 symptom-specific items
      and from 4 to 10 functional impairment items. The original 9-point severity scale
      was revised to 7 points. Two global severity questions bring the item count to
      44. The instrument fits comfortably on the front and back of a single sheet of
      paper. CONCLUSIONS: The Wisconsin Upper Respiratory Symptom Survey (WURSS) is
      ready for formal validity testing or practical use in common cold research.

PMID- 11978239
TI  - Do primary care physicians underprescribe antibiotics for peptic ulcer disease?
      Report from an Italian research network.
AB  - OBJECTIVE: To determine how often primary care physicians prescribe eradication
      therapy for peptic ulcer disease (PUD) and nonulcer dyspepsia (NUD). STUDY
      DESIGN: During a 2-year period (1998-2000) we analyzed data concerning patients
      with PUD or NUD seen by 80 Italian primary care physicians uniformly distributed
      throughout the country. We classified patients as having a definitive or a
      presumptive diagnosis on the basis of the completeness of the diagnostic workup
      and interpreted the prescription of antibiotics for dyspepsia as evidence of
      attempted eradication of Helicobacter pylori. POPULATION: Consecutive ambulatory
      patients. OUTCOMES MEASURED: The frequency with which predefined groups of
      patients received eradication therapy. RESULTS: Of 6866 patients, 690 (10%)
      received eradication therapy. Of 2162 patients with PUD, 596 (27.6%) received
      eradication therapy; of 4704 patients with NUD, however, only 94 (2%) received
      this treatment (P =.0001). A total of 341 (37.7%) of 904 PUD patients with a
      definitive diagnosis were given eradication therapy and 255 (20.3%) of 1258 PUD
      patients with a presumptive diagnosis were given therapy (P &lt.0001). In NUD
      patients, 7 of 743 (0.9%) with a definitive diagnosis received eradication
      therapy, while 87 (2.2%) of 3961 of those with a presumptive diagnosis were given
      the same therapy (P =.025). CONCLUSIONS: While Italian primary care physicians
      appropriately target eradication therapy for H pylori infection in patients with
      peptic ulcer disease rather than nonulcer disease, the intervention was still
      underused in these patients. Improvements in this prescribing behavior are
      needed.

PMID- 11978240
TI  - Approach to the perimenopausal patient.

PMID- 11978241
TI  - Are SSRIs and TCAs equally effective for the treatment of panic disorder?

PMID- 11978242
TI  - In children hospitalized for asthma exacerbations, does adding ipratropium
      bromide to albuterol and corticosteroids improve outcome?

PMID- 11978243
TI  - Which is more effective for as-needed treatment of seasonal allergy symptoms:
      intranasal corticosteroids or oral antihistamines?

PMID- 11978244
TI  - Are paroxetine, fluoxetine, and sertraline equally effective for depression?

PMID- 11978245
TI  - Prevention of osteoporosis.

PMID- 11978246
TI  - What is the best diet to prevent recurrent calcium oxalate stones in patients
      with idiopathic hypercalciuria?

PMID- 11978247
TI  - What is the relative cardiovascular benefit of lowering cholesterol, blood
      pressure, and glucose levels in patients with type 2 diabetes?

PMID- 11978248
TI  - Which is most effective of osteoarthritis of the knee: rofecoxib, celecoxib, or
      acetaminophen?

PMID- 11978249
TI  - Which oral antihyperglycemics are most efficacious in reducing hemoglobin A1C in
      diabetic patients?

PMID- 11978250
TI  - Clinical inquiries. When should acute nonvenereal conjunctivitis be treated with
      topical antibiotics?

PMID- 11978251
TI  - Clinical inquiries. What is the most effective treatment for external genital
      warts?

PMID- 11978252
TI  - Clinical inquiries. What are the indications for tonsillectomy in children?

PMID- 11978253
TI  - Does amoxicillin improve outcomes in patients with purulent rhinorrhea? A
      pragmatic randomized double-blind controlled trial in family practice.
AB  - OBJECTIVE: To compare the efficacy of amoxicillin vs placebo in patients with an
      acute upper respiratory tract infection and purulent rhinorrhea. STUDY DESIGN:
      Double-blind randomized placebo-controlled trial. POPULATION: The 416 patients
      included from 69 family practices were 12 years or older, presenting with acute
      upper respiratory complaints, and having a history of purulent rhinorrhea and no
      signs of complications of sinusitis. OUTCOMES MEASURED: Therapy success
      (disappearance of symptoms that most greatly affected the patient's health) at
      day 10 and duration of general illness, pain, and purulent rhinorrhea. RESULTS:
      Therapy was successful in 35% of patients with amoxicillin and in 29% of patients
      with placebo (relative risk [RR] 1.14, 95% confidence interval [CI], 0.92-1.42).
      There was no effect on duration of general illness or pain. Duration of purulent
      rhinorrhea was shortened by amoxicillin (9 days vs 14 for clearing of purulent
      rhinorrhea in 75% of patients; P =.007). Diarrhea was more frequent with
      amoxicillin (29% vs 19%, RR 1.28, 95% CI, 1.05-1.57). No complications were
      reported. One patient (0.5%) receiving amoxicillin and 7 (3.4%) receiving placebo
      discontinued trial therapy because of exacerbation of symptoms (RR 0.25, 95% CI
      0.04-1.56, P =.07). All 8 patients recovered with antibiotic therapy.
      CONCLUSIONS: Amoxicillin has a beneficial effect on purulent rhinorrhea caused by
      an acute infection of the nose or sinuses but not on general recovery. The
      practical implication is that all such patients, whatever the suspected
      diagnosis, can be safely treated with symptomatic therapy and instructed to
      return if symptoms worsen.

PMID- 11978254
TI  - Do delayed prescriptions reduce the use of antibiotics for the common cold? A
      single-blind controlled trial.
AB  - OBJECTIVE: To test the use of a delayed prescription compared with instructions
      to take antibiotics immediately in patients presenting to family physicians with
      upper respiratory tract infections (common colds). STUDY DESIGN: Randomized
      controlled single-blind study. POPULATION: Subjects were 129 patients presenting
      with the common cold who requested antibiotics or whose physicians thought they
      wanted them. All patients were in a family practice in Auckland, New Zealand,
      consisting of 15 physicians (9 male, 6 female) who had completed medical school
      between 1973 and 1992. OUTCOMES MEASURED: Outcomes were antibiotic use (taking at
      least 1 dose of the antibiotic), symptom scores, and responses to the
      satisfaction questions asked at the end of the study. RESULTS: Patients in the
      delayed-prescription group were less likely to use antibiotics (48%, 95% CI, 35%
      60%) than were those instructed to take antibiotics immediately (89%, 95% CI, 76%
      94%). Daily body temperature was higher in the immediate-prescription group. The
      lack of difference in the symptom score between the 2 groups suggests that there
      is no danger in delaying antibiotic prescriptions for the common cold.
      CONCLUSIONS: Delayed prescriptions are a safe and effective means of reducing
      antibiotic consumption in patients with the common cold. Clarification of patient
      expectations for antibiotics may result in a lower prescription rate. When the
      patient demands a prescription, delaying its delivery has the potential to
      provide gentle education.

PMID- 11978256
TI  - Where next with antibiotics and respiratory tract infections?

PMID- 11978255
TI  - Is roxithromycin better than amoxicillin in the treatment of acute lower
      respiratory tract infections in primary care? A double-blind randomized
      controlled trial.
AB  - OBJECTIVE: To assess the efficacy of roxithromycin relative to amoxicillin. STUDY
      DESIGN: We conducted a double-blind randomized controlled trial of oral 500 mg
      amoxicillin 3 times per day vs oral 300 mg roxithromycin once a day for 10 days.
      POPULATION: We included 196 adults who had presented to a general practitioner
      with lower respiratory tract infection (LRTI) and, in the physician's opinion,
      needed antibiotic treatment. OUTCOMES MEASURED: We measured clinical response
      after 10 and 28 days, defined in 4 ways: (1) decrease in LRTI symptoms; (2)
      complete absence of symptoms; (3) decrease in signs; and (4) complete absence of
      signs. Self-reported response included the decrease in symptoms and the time
      until resumption of impaired or abandoned daily activities on days 1 through 10,
      21, and 27. RESULTS: Clinical cure rates after the completion of antibiotic
      treatment (10 days) were not significantly different for the 2 groups. After 28
      days, the roxithromycin group showed no increase in cure rate as evidenced by the
      decrease in symptoms, indicating a significantly lower cure rate. However, this
      difference did not alter physicians' overall conclusion after complete follow-up
      that 90% of patients, regardless of age, had been effectively treated with either
      amoxicillin or roxithromycin. CONCLUSIONS: The surplus value of roxithromycin was
      not confirmed. Amoxicillin remains a reliable first-choice antibiotic in the
      treatment of LRTI in general practice.

PMID- 11978257
TI  - Effect on antibiotic prescribing of repeated clinical prompts to use a sore
      throat score: lessons from a failed community intervention study.
AB  - OBJECTIVES: Infections with group A streptococcus (GAS) occur in 10% to 20% of
      patients with sore throats, whereas antibiotics are prescribed 50% of the time.
      Clinical scoring rules can more accurately predict the likelihood of GAS
      infection, but whether family physicians will adopt such approaches is unclear.
      This study sought to determine whether repeated clinical prompts to use a scoring
      approach could help family physicians lower antibiotic use in patients with a
      sore throat. STUDY DESIGN: Randomized trial in which physicians were assigned to
      use either (1) chart stickers that prompted them to calculate a score based on
      clinical findings and provided management recommendations linked to score totals
      or (2) a clinical checklist. POPULATION: Ninety-seven family physicians in
      Ontario, Canada, assessed 621 children and adults with sore throat and obtained a
      throat swab for culture. OUTCOMES MEASURED: (1) Unnecessary antibiotic
      prescriptions given to patients with a negative throat culture and (2) overall
      antibiotic use. RESULTS: There were no differences between the control and
      intervention group in unnecessary antibiotic prescriptions (16.1% vs 20.4%,
      respectively, P =.29) or overall antibiotic use (27.9% vs 28.1%, P =.97).
      However, a number of physicians dropped out of the study; as a result, the
      characteristics of the physicians in the 2 groups were dissimilar in factors
      related to prescribing. After adjusting for these differences and patient
      clustering by physician, the odds ratio for the effect of the intervention on
      unnecessary antibiotic prescriptions was 0.76 (95% confidence interval [CI] =
      0.42, 1.40) and 0.57 for overall antibiotic use (95% CI = 0.27, 1.17).
      CONCLUSIONS: Chart prompts during clinical encounters to use a clinical score in
      the assessment of patients with a sore throat did not reduce unnecessary
      antibiotic prescribing by family physicians. The problems encountered in
      conducting this community-based intervention trial are discussed in relation to
      the negative result.

PMID- 11978258
TI  - How common is hip pain among older adults? Results from the Third National Health
      and Nutrition Examination Survey.
AB  - OBJECTIVE: To determine the incidence of self-reported significant hip pain using
      a nationally representative sample of older adults in the United States. STUDY
      DESIGN: Subjects were interviewed to determine their leisure time physical
      activity levels and whether they experienced severe hip pain. Sampling weights
      were calculated to account for unequal selection probabilities. The impact of
      race, age, and physical activity status was examined as influential factors
      affecting hip pain. POPULATION: We interviewed 6596 adults aged 60 years and
      older as part of the third National Health and Nutrition Examination Survey
      (NHANES III). OUTCOME MEASURED: We measured the prevalence of hip pain. RESULTS:
      A total of 14.3% of participants aged 60 years and older reported significant hip
      pain on most days over the past 6 weeks. Men reported hip pain less frequently
      than women. Age did not influence self-reported hip pain in men. The lowest
      prevalence of hip pain was found in women aged 60 to 70 years. Sixteen percent of
      non-Hispanic white women reported hip pain, compared with 14.8% of black women
      and 19.3% of Mexican American women. Among non-Hispanic white men, 12.4% reported
      hip pain, a proportion no different from that of their black and Mexican American
      male counterparts. Among older US adults, 18.4% of those who had not participated
      in leisure time physical activity during the previous month reported severe hip
      pain; 12.6% of those who did engage in physical activity reported hip pain.
      CONCLUSIONS: Self-reported hip pain has increased since NHANES I (1971-1975).
      Further studies are needed to identify individuals at highest risk for severe hip
      pain and to identify optimal treatment of hip pain.

PMID- 11978260
TI  - Weekly versus daily dosing of atorvastatin.
AB  - Twenty-four consecutive patients of a single family physician who had achieved
      NCEP-II goal levels of low-density lipoprotein cholesterol (LDL-C) on a daily
      atorvastatin dose of 10 mg for at least 6 months were invited to switch to 20 mg
      weekly. Mean LDL levels for the 22 patients who completed the trial had been
      reduced by 43% from baseline on 10 mg daily (P <.05) and were reduced by 22% from
      baseline on the seventh day following the last weekly dose of 20 mg (P <.05).
      Total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratios were
      reduced by 31% and 17%, respectively (both P <.05) and triglycerides by 20% and
      10% (both P <.05).

PMID- 11978259
TI  - Do whole-grain oat cereals reduce the need for antihypertensive medications and
      improve blood pressure control?
AB  - OBJECTIVES: Our study compared 2 whole grain oat-based cereals with 2 refined
      grain wheat-based cereals to determine their effects on the need for
      antihypertensive medications in people with high blood pressure (BP). STUDY
      DESIGN: This 12-week, randomized controlled parallel-group trial with = 6 weeks
      of voluntary follow-up was designed to investigate the antihypertensive effects
      of oats. After 4 weeks of baseline feeding, medication dose was maintained or
      reduced by half or completely throughout the middle 4 weeks of the study. In the
      final 4 weeks, participants continued cereal consumption; medication was adjusted
      according to the protocol. POPULATION: Men and women (n = 88) being treated for
      hypertension with a mean baseline BP below 160/100. OUTCOMES MEASURED: Primary
      study outcomes included change in SBP and DBP as well as antihypertensive
      medication reduction. Secondary measures included blood lipid, fasting glucose,
      and insulin levels and side effects related to elevated BP and increased dietary
      fiber intake. RESULTS: Seventy-three percent of participants in the oats group
      versus 42% in the control group were able to stop or reduce their medication by
      half. Treatment group participants whose medication was not reduced had
      substantial decreases in BP. The oats group experienced a 24.2-mg/dL reduction in
      total cholesterol levels, a 16.2-mg/dL decrease in low-density lipoprotein
      cholesterol levels, and a 15.03-mg/dL drop in plasma glucose levels vs controls.
      CONCLUSIONS: Results suggest that a diet containing soluble fiber-rich whole oats
      can significantly reduce the need for antihypertensive medication and improve BP
      control. Considering the lipid and glucose improvements as well, increased
      consumption of whole oats may significantly reduce cardiovascular disease risk.

PMID- 11978261
TI  - Involvement of family and community medicine professionals in community projects.
AB  - OBJECTIVE: Medical schools are being challenged to continue their excellence in
      education, research, and patient care while responding to the health needs of the
      public. The objective of our study was to determine the nature and type of
      community involvement of professionals in departments of family and community
      medicine. STUDY DESIGN: We mailed a 24-item structured survey to a random
      national sample of family medicine professionals. POPULATION: Survey recipients
      included 770 full-time physician and nonphysician active members of the Society
      of Teachers of Family Medicine. OUTCOMES MEASURED: Our survey assessed community
      activities, challenges and incentives to those activities, and desired resources
      for working in the community. RESULTS: A total of 446 usable surveys were
      returned (58% response rate). Ninety-five percent of respondents had participated
      in a community activity within the previous year. More male respondents precepted
      medical students or residents and educated faculty on topics regarding community
      education; more older respondents participated by sitting on community health
      boards or councils. Insufficient release time and lack of funding were the 2 most
      frequently cited barriers to community-based activities. CONCLUSIONS: Most
      faculty are involved in community-related teaching and service. Reasons for low
      levels of research and subgroup differences, especially among women and young
      faculty, merit further research.

PMID- 11978262
TI  - Oat ingestion reduces systolic and diastolic blood pressure in patients with mild
      or borderline hypertension: a pilot trial.
AB  - OBJECTIVES: We assessed the short-term antihypertensive effects of soluble fiber
      rich whole oat cereals when added to a standard American diet. In addition,
      multiple assessments of insulin sensitivity were conducted. STUDY DESIGN: This
      was a randomized, controlled, parallel-group pilot study designed to compare an
      oat cereal group (standardized to 5.52 g/day beta-glucan) to a low-fiber cereal
      control group (less than 1.0 g/day total fiber) over 6 weeks. POPULATION: A total
      of 18 hypertensive and hyperinsulinemic (= 10  U/mL or more) men and women
      completed the trial. OUTCOMES MEASURED: Primary study outcomes were changes in
      systolic blood pressure (SBP) and diastolic blood pressure (DBP). Secondary
      outcomes included blood lipid, fasting glucose, and insulin levels and side
      effects related to elevated blood pressure and increased dietary fiber intake.
      RESULTS: The oat cereal group experienced a 7.5 mm Hg reduction in SBP (P &lt.01)
      and a 5.5 mm Hg reduction in DBP (P &lt.02), while there was virtually no change
      in either SBP or DBP in the control group. In the oat cereal group, a trend was
      observed for a lower total insulin response to a glucose load, suggesting
      improved insulin sensitivity. However, this could not be confirmed using
      estimates from the Bergman Minimal Model, perhaps because of our small sample
      size. The oats group experienced a significant reduction in both total
      cholesterol (9%) and low-density lipoprotein cholesterol (14%). CONCLUSIONS: The
      addition of oat cereals to the normal diet of patients with hypertension
      significantly reduces both SBP and DBP. Soluble fiber-rich whole oats may be an
      effective dietary therapy in the prevention and adjunct treatment of
      hypertension.

PMID- 11978263
TI  - Treatment of hyperlipidemia.
AB  - In 1995 and 1996, US adults made more than 18 million office visits for the
      evaluation and treatment of hyperlipidemia, including 3.4% of all visits to
      family physicians. Among visits to family physicians, 4.1% included measurement
      of cholesterol levels.(1) Overall, mean cholesterol levels decreased from 220 in
      1960-1962 to 203 in 1988-1994. During the same time period, the proportion of
      adults with elevated total cholesterol levels (> 240) decreased from 32% to
      19%.(2) Despite this progress, the availability of more effective drugs,
      guidelines advocating increasingly aggressive treatment, and population-wide
      goals established in Healthy People 2010 will continue to increase the number of
      patients seen by family physicians for screening, diagnosis, and treatment of
      hyperlipidemia.

PMID- 11978264
TI  - Evidence-based medicine web site.

PMID- 11978265
TI  - Liquid-based cervical cytology tests.

PMID- 11978266
TI  - Can a patient information sheet reduce antibiotic use in adult outpatients with
      acute bronchitis?

PMID- 11978267
TI  - Is splinting of distal radius torus fractures an acceptable alternative to
      casting?

PMID- 11978268
TI  - Is lansoprazole (Prevacid) or omeprazole (Prilosec) more effective in treating
      erosive esophagitis?

PMID- 11978269
TI  - Do intranasal corticosteroids aid treatment of acute sinusitis in patients with a
      history of recurrent sinus symptoms?

PMID- 11978272
TI  - Third-trimester unexplained intrauterine fetal death is associated with inherited
      thrombophilia.
AB  - OBJECTIVE: To determine the risk of thrombophilias in women with unexplained
      intrauterine fetal deaths (IUFD). METHODS: All women with IUFD at 27 weeks'
      gestation or greater were initially assessed during a period of 26 months.
      Subjects with multiple pregnancies, congenital anomalies, intrauterine infection,
      chorioamnionitis, immune hydrops, diabetes mellitus, previous thromboembolism,
      and severe hypertensive disease were excluded. The remaining 40 women with
      unexplained IUFD (study group) were matched for age and ethnicity with 80 healthy
      women who had at least one normal pregnancy (control group). All participants
      were tested at least 2 months after delivery for mutations of factor V Leiden,
      prothrombin gene, methylenetetrahydrofolate reductase, and for deficiencies of
      protein S, protein C, and antithrombin III. They were also tested and found to be
      negative for anticardiolipin antibodies. RESULTS: The gestational age at delivery
      and birth weight were significantly lower in the study group. The prevalence of
      inherited thrombophilias was 42.5% in the study group compared with 15% in the
      control group (odds ratio 2.8, 95% confidence interval 1.5, 5.3, P =.001). The
      prothrombin mutation and protein S deficiency rates were significantly higher in
      the study group (odds ratio 2.3, 95% confidence interval 1.3, 4.0, and odds ratio
      3.2, 95% confidence interval 2.4, 4.1, respectively). CONCLUSION: Third-trimester
      IUFD is significantly associated with thrombophilias. These findings suggest that
      thrombophilia work-ups should be part of IUFD investigations and may have
      therapeutic and prognostic implications in future pregnancies.

PMID- 11978273
TI  - Neonatal organ system injury in acute birth asphyxia sufficient to result in
      neonatal encephalopathy.
AB  - OBJECTIVE: To identify the proportion of major organ system injury in cases of
      acute intrapartum asphyxia that result in neonatal encephalopathy. METHODS: A
      prospectively maintained database was cross-referenced using medical record
      coding to identify diagnoses of acute intrapartum asphyxia, acute birth asphyxia,
      or neonatal encephalopathy over a 6-year period. An acute intrapartum asphyxial
      antecedent was validated with emphasis on excluding long-standing or chronic
      conditions where injury likely occurred before presentation. Injury pattern was
      evaluated using routinely available laboratory and imaging tests. RESULTS: Forty
      six cases of acute peripartum asphyxia sufficient to result in the diagnosis of
      neonatal encephalopathy were identified. Clinical central nervous system injury
      resulting in encephalopathy was present in 100% of cases as it was an entry
      criteria; of these, 49% had electroencephalogram and 40% had imaging studies
      diagnostic of acute injury. Liver injury based on elevated aspartate transaminase
      or alanine transaminase levels occurred in 80%. Heart injury, as defined by
      pressor or volume support beyond 2 hours of life or elevated cardiac enzymes,
      occurred in 78%. Renal injury, defined by an elevation of serum creatinine to
      greater than 1.0 mg/dL, persistent hematuria, persistent proteinuria, or clinical
      oliguria, occurred in 72%. An elevation in nucleated red blood cell counts
      exceeding 26 per 100 white blood cells occurred in 41%. CONCLUSION: Using common
      diagnostic tests as markers of acute asphyxial injury, we noted that multiple
      organs suffer damage during an acute intrapartum asphyxial event sufficient to
      result in a neonatal encephalopathy.

PMID- 11978274
TI  - Persistence of placenta previa according to gestational age at ultrasound
      detection.
AB  - OBJECTIVE: To evaluate gestational age at ultrasound detection of placenta previa
      as a predictor of previa persistence until delivery, and to estimate the effects
      of previa type, parity, and prior cesarean delivery on previa persistence.
      METHODS: This was a retrospective cohort study of pregnancies with placenta
      previa detected during transabdominal or endovaginal ultrasound examination.
      Previa was categorized as complete if the placenta completely covered the
      internal cervical os or incomplete if the inferior placental edge partially
      covered or reached the margin of the os. Gestational age was grouped into 4-week
      intervals from 15 to 36 weeks. The outcome was cesarean delivery for persistent
      previa. RESULTS: Previa was detected during 940 ultrasound examinations in 714
      pregnancies. Of those with placenta previa at 15-19 weeks, 20-23 weeks, 24-27
      weeks, 28-31 weeks, and 32-35 weeks, previa persisted until delivery in 12%, 34%,
      49%, 62%, and 73%, respectively. At each interval, complete previa was more
      likely to persist than incomplete previa, all P <.001. Prior cesarean delivery
      was an independent risk factor for persistent previa among women diagnosed with
      previa in the second trimester, P <.05. However, parity was not an independent
      risk factor for persistence at any gestational age interval after adjusting for
      prior cesarean delivery. CONCLUSION: Gestational age at ultrasound detection of
      placenta previa may be used to predict likelihood of previa persistence. After
      midpregnancy, risk of persistence appears to be higher than previously reported.
      Type of placentation and prior cesarean delivery are important factors that
      modify the risk that previa will complicate delivery.

PMID- 11978275
TI  - Survival of other fetuses after a fetal death in twin or triplet pregnancies.
AB  - OBJECTIVE: To estimate the frequency of fetal death in multifetal pregnancies and
      the probability of survival to age 1 year for twins or triplets in which at least
      one fetal death occurred at 20 weeks' gestation or more. METHODS: We used the
      Matched Multiple Birth File from the US National Center for Health Statistics,
      which included 152,233 sets of twins and 5356 sets of triplets registered from
      1995 to 1997. The Cox proportional hazards model was used to estimate the
      adjusted relative risk of death before age 1 year for remaining twins and
      triplets. RESULTS: Fetal death at 20 weeks' gestation or later was uncommon,
      occurring in 2.6% of twin and 4.3% of triplet gestations. After adjustment for
      confounders, the survival of the remaining fetuses was inversely related to the
      time of the first fetal demise. Same-sex twins were two times more likely than
      opposite-sex twins to die after an intrauterine demise at 25-32 weeks' gestation
      and were more than three times more likely to die after a death at 33 weeks'
      gestation or more. CONCLUSION: After a fetal death in a multifetal pregnancy at
      20 weeks' gestation or later, the survival of the remaining fetuses is inversely
      related to the time the death occurred. Among twins, survival also depends on sex
      concordance, with opposite-sex twins more likely than same-sex twins to survive.

PMID- 11978276
TI  - A randomized controlled trial of early oral analgesia in gynecologic oncology
      patients undergoing intra-abdominal surgery.
AB  - OBJECTIVE: To evaluate the safety and efficacy of early oral analgesia after
      intra-abdominal surgery in gynecologic oncology patients. METHODS: Over a 2.5
      year period, 227 gynecologic oncology patients undergoing intra-abdominal surgery
      were enrolled in a randomized controlled trial of early oral versus traditional
      parenteral analgesia. All patients initially received parenteral morphine via a
      patient-controlled analgesia (PCA) pump with a basal dose of 0.5 mg/h and a PCA
      dose of 1 mg with a 10-minute lockout. On the first postoperative day, all
      patients began a clear liquid diet, which was advanced as tolerated. Patients
      allocated to early oral analgesia were switched from parenteral to oral morphine.
      They received a scheduled dose of 20 mg every 4 hours with an additional dose of
      10 mg every 2 hours as needed for breakthrough pain. Patients allocated to
      traditional parenteral analgesia continued to receive parenteral morphine via a
      PCA pump with basal and PCA doses. On the second postoperative day, the scheduled
      oral and basal parenteral doses were discontinued. The oral and parenteral PCA
      doses were continued until 24 hours before discharge, at which time the patient
      was switched to oxycodone 5 mg/acetaminophen 325 mg. RESULTS: There were no
      significant differences among the groups in any demographic or clinical indices,
      including age, case distribution, surgery length, blood loss, time to return of
      bowel function, length of hospital stay, pain, sedation, and satisfaction scores,
      and incidence of nausea, vomiting, or major postoperative complications.
      CONCLUSIONS: Early oral analgesia in gynecologic oncology patients undergoing
      intra-abdominal surgery is safe and efficacious.

PMID- 11978277
TI  - Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long
      term follow-up.
AB  - OBJECTIVE: To assess post-treatment effects in endometriosis patients of a 12
      month course of GnRH agonist alone or with one of three "add-back" regimens.
      METHODS: This is a post-treatment follow-up analysis of a randomized, double
      masked, placebo-controlled 52-week trial. All patients had received monthly
      leuprolide acetate and were randomized to one of four groups: A-daily placebo; B
      daily norethindrone acetate 5 mg; C-daily norethindrone acetate 5 mg and
      conjugated equine estrogens 0.625 mg; and D-daily norethindrone acetate 5 mg and
      conjugated equine estrogens 1.25 mg. Of 201 patients enrolled in the initial
      trial, 123 completed at least 280 days of therapy and entered the follow-up
      period. Physical findings and symptoms were quantified, and lumbar spine bone
      mineral density was determined at intervals for up to 12 and 24 months post
      therapy. RESULTS: Symptom and pelvic examination scores remained significantly
      below baseline for at least 8 months after completion of therapy for all four
      groups (P <.05). Findings were not affected by endometriosis scores noted on
      screening laparoscopy. Mean bone mineral density values remained at or above
      baseline in all add-back groups. The significant mean loss in bone density in
      group A during therapy reversed slowly and had not returned to baseline at the
      final follow-up visit (P <.001). CONCLUSION: GnRH agonist and norethindrone
      acetate alone or combined with low-dose conjugated equine estrogens administered
      to symptomatic endometriosis patients for 12 months provides extended pain relief
      and bone mineral density preservation after completion of therapy.

PMID- 11978278
TI  - Meeting the needs of young women with secondary amenorrhea and spontaneous
      premature ovarian failure.
AB  - OBJECTIVE: To investigate the experiences of young women with spontaneous
      premature ovarian failure with regard to the initial presenting symptom,
      promptness of diagnosis, and patient education. METHODS: We asked 50 patients
      previously diagnosed with spontaneous premature ovarian failure to participate in
      a structured interview survey consisting of 38 true-or-false, multiple-choice,
      and open-ended questions. RESULTS: Disturbance in menstrual pattern was the most
      common initial symptom in the 48 women who completed the interview (44 of 48,
      92%). Over half of the 44 women who presented with this complaint reported
      visiting a clinician's office three or more times before laboratory testing was
      performed to determine the diagnosis. Over half of them reported seeing three or
      more different clinicians before diagnosis. In 25% of women it took longer than 5
      years for the diagnosis of premature ovarian failure to be established. Patients
      who spent more than 5 minutes with the clinician discussing the diagnosis were
      significantly more likely to be satisfied with the manner in which they were
      informed (P <.001). Ninety percent of participants were college graduates, and
      40% had graduate degrees. CONCLUSION: Women with spontaneous premature ovarian
      failure perceived a need for more aggressive evaluation of secondary amenorrhea
      and oligomenorrhea. Loss of menstrual regularity can be a sign of ovarian
      insufficiency, and the associated estrogen deficiency is a well-established risk
      factor for osteoporosis.

PMID- 11978279
TI  - The association between serum estradiol level and hearing sensitivity in
      postmenopausal women.
AB  - OBJECTIVE: To estimate whether hearing sensitivity in postmenopausal women is
      associated with serum estradiol level or bone mineral density. METHODS: Serum
      estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck,
      and hearing sensitivity were measured in 1830 postmenopausal women. Serum
      estradiol level was measured by radioimmunoassay, and dual energy x-ray
      absorptiometry was used to measure bone mineral densities of the lumbar vertebrae
      and femoral neck. Hearing sensitivity was evaluated by pure tone audiometry. Age,
      serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral
      neck, and the proportion of women on hormone replacement therapy were analyzed in
      women with and without hearing loss. RESULTS: On univariate analysis, significant
      differences were found in mean age, serum estradiol level, bone mineral densities
      of the lumbar vertebrae and femoral neck, and the proportion of women on hormone
      replacement therapy between the two groups (mean +/- standard deviation, 59.4 +/-
      5.6 versus 56.9 +/- 4.7 years, P <.001; 8.4 +/- 3.8 versus. 9.9 +/- 8.7 pg/mL, P
      <.001; 0.85 +/- 0.14 versus 0.88 +/- 0.15 g/cm(2), P <.01; 0.65 +/- 0.10 versus
      0.68 +/- 0.10 g/cm(2), P <.005; 0.006% versus 0.03%, P <.05, respectively). On
      multiple logistic regression analysis, significant association was found between
      age and hearing loss and between serum estradiol level and hearing loss (P <.001,
      P =.02, respectively). CONCLUSION: This study suggests that a lower level of
      serum estradiol possibly impedes hearing sensitivity in postmenopausal women.

PMID- 11978280
TI  - Changing obstetric practices associated with decreasing incidence of meconium
      aspiration syndrome.
AB  - OBJECTIVE: To describe changes in neonatal and obstetric practices that may have
      contributed to the decreasing incidence of meconium aspiration syndrome in our
      population during this time. METHODS: We compared neonatal and obstetric
      characteristics of 61 infants diagnosed with meconium aspiration syndrome with
      1365 infants born through moderate or thick meconium-stained amniotic fluid at
      more than 37 weeks' completed gestation. Data were prospectively collected, and
      all respiratory diagnoses were concurrently made. Three distinct birth year
      groups were analyzed based on changing obstetric practice paradigms. RESULTS:
      Meconium aspiration syndrome decreased nearly four-fold from 1990-1992 to 1997
      1998 (5.8% to 1.5% of meconium-stained infants more than 37 weeks; P <.003). The
      only change in neonatal characteristics was a 33% decrease in births more than 41
      weeks with a reciprocal 33% increase in births 38-39 weeks during 1997-1998.
      Significant changes in obstetric practice included more frequent diagnosis of
      nonreassuring fetal heart rate patterns, greater use of amnioinfusion, and
      increased cesarean delivery rate in 1997-1998. By logistic regression analysis,
      the only consistent risk factor for meconium aspiration syndrome across all three
      epochs was the presence of tracheal meconium. CONCLUSION: Reduction in post-term
      delivery was the most important factor in reducing meconium aspiration syndrome.

PMID- 11978281
TI  - Ultrasonographic prediction of birth weight in diabetic pregnancies.
AB  - OBJECTIVE: To compare diabetic and nondiabetic pregnant women near term regarding
      the accuracy of predicted birth weight by the gestation-adjusted projection
      method using ultrasonographic measurements. METHODS: Patients with singleton
      pregnancies who had diabetes and who underwent sonograms between 34.0 weeks and
      36.9 weeks formed the study group. The control group was comprised of nondiabetic
      women who had sonograms in the same gestational age range. The absolute birth
      weight errors and absolute percent errors in the study group and the controls
      were compared with t tests. RESULTS: A total of 133 diabetic women and 1690
      controls were included in the study. The mean (+/- standard deviation) absolute
      error of the predicted birth weight was 265 +/- 210 g in the diabetic women and
      261 +/- 204 g in the control group (P =.87). The mean (+/- standard deviation)
      absolute percent error was 7.4% +/- 6.3% for diabetic women compared with 8.3% +/
      6.6% for the controls (P =.14). CONCLUSION: Prediction of birth weight using the
      gestation-adjusted projection method is as accurate in diabetic women as in
      controls.

PMID- 11978282
TI  - Pfannenstiel versus Maylard incision for cesarean delivery: A randomized
      controlled trial.
AB  - OBJECTIVE: To compare the Pfannenstiel incision with transverse muscle-cutting
      Maylard incision in women who had cesarean delivery. METHODS: Patients were
      assigned randomly to a Pfannenstiel or Maylard incision. Postoperative treatment
      was similar for each group. Surgical characteristics, complications,
      postoperative pain (visual analog scale, analgesic use), and related quality of
      life (1- and 3-month self-administered questionnaires) were analyzed. Abdominal
      wall muscle recovery was compared objectively by dynamometer. RESULTS: Fifty-four
      women had a Pfannenstiel incision and 43 had the Maylard incision. There were no
      differences in intraoperative characteristics, postoperative morbidity, or pain.
      Women's responses to the Nottingham Health Profile questionnaire at 1 and 3
      months postoperatively and clinical and isokinetic testing for abdominal wall
      strength were similar between the two groups. CONCLUSION: Transecting the rectus
      muscle was no more deleterious than the Pfannenstiel incision. There was no
      difference in objectively measured abdominal wall strength.

PMID- 11978283
TI  - The effect of cigarette smoking on fetal heart rate characteristics.
AB  - OBJECTIVE: To evaluate the effect of repeated cigarette smoking on fetal heart
      rate (FHR) characteristics. METHODS: Fifteen chronic smokers who were between 28
      and 36 weeks' gestation were evaluated during an 8-hour smoking session. Baseline
      FHR and reactivity were evaluated before an initial cigarette and 4 hours later
      (after the fourth cigarette), when the effects of smoking on FHR were expected to
      be maximal. Plasma nicotine was measured at baseline and repeated at times of
      fetal monitoring. RESULTS: Subjects smoked a mean +/- standard deviation of 22 +/
      6 cigarettes per day. They abstained from smoking for 9.2 +/- 3.2 hours before
      evaluation. The initial baseline FHR was 134 +/- 9 beats per minute versus 135 +/
      11 beats per minute after the fourth cigarette (P =.17). Plasma nicotine
      increased from 2.6 +/- 5.6 ng/mL to 24 +/- 9.9 ng/mL after the fourth cigarette
      (P <.001). The initial nonstress test was reactive in 12 of 15 (80%) of the
      fetuses. After the fourth cigarette, only four of 15 (27%) of the nonstress tests
      were reactive. A majority of tracings (eight of 15) were initially reactive
      before smoking and became nonreactive after smoking. Some tracings remained
      nonreactive (three of 15), and some tracings remained reactive (four of 15) at
      both assessments. None of the tracings that were initially nonreactive became
      reactive. The change in reactivity was significant (P =.013). CONCLUSION: Acute,
      repeated smoking decreases FHR reactivity.

PMID- 11978284
TI  - Autologous blood transfusion in radical hysterectomy with and without
      erythropoietin therapy.
AB  - OBJECTIVE: To investigate whether preoperative treatment with erythropoietin
      facilitates the collection of a sufficient amount of autologous blood in a short
      period of time. METHODS: Forty-one women scheduled for radical hysterectomy were
      randomized to preoperative autologous blood donation with or without preoperative
      recombinant human erythropoietin therapy. All patients were scheduled to deposit
      three units of blood within 2 weeks before surgery. Hemoglobin, erythrocyte
      volume fraction, blood cells, iron status, and hemolysis were analyzed before and
      after surgery. RESULTS: Hemoglobin levels decreased continuously in both groups
      after the first autologous donation until day 1 postoperatively. With
      erythropoietin therapy, the erythrocyte volume fraction and hemoglobin levels
      were significantly higher during precollection and day 1 after surgery.
      Preoperatively, the drop was 12 g/L less in the erythropoietin-treated group. The
      additional use of erythropoietin therapy reduced the inability of patients to
      predeposit blood from 17.8% to 3.4%. CONCLUSION: Most women can predeposit three
      units of whole blood in only 2 weeks without obtaining severe anemia. By treating
      women with erythropoietin, one out of seven can be prevented from a hemoglobin
      level below the 100 g/L limit for donation.

PMID- 11978286
TI  - Utility and cost-effectiveness of preoperative autologous blood donation in
      gynecologic and gynecologic oncology patients.
AB  - OBJECTIVE: To evaluate utility and cost-effectiveness of preoperative autologous
      blood donation in gynecologic and gynecologic oncology patients. METHODS:
      Pheresis unit records were retrospectively reviewed to identify all women who
      performed autologous blood donation. Clinical charts were abstracted. Use rate
      (number of units used/number of units donated) and quality-adjusted life years
      were calculated. Statistical analysis consisted of chi(2), Student t, and Fisher
      exact tests. RESULTS: A total of 106 women with benign (n = 63) and malignant
      disease (n = 43) donated 143 units (1.4 units per patient) of which 126 (88%)
      were discarded. Fifteen patients (14%) were transfused a total of 24 units, 17
      autologous (71%) and seven allogeneic (29%). Those transfused had a significantly
      higher estimated blood loss (700 mL versus 275 mL, P <.001), lower nadir
      hemoglobin (7.9 versus 9.6, P <.001), and longer hospital stay (4.9 days versus
      4.0 days, P =.05). Despite similar estimated blood loss (370 mL versus 310 mL),
      the use rate for malignant versus benign disease was significantly greater (0.31
      versus 0.07, P =.005). Radical versus nonradical surgery had a significantly
      higher estimated blood loss (620 mL versus 250 mL, P =.001) and use rate (0.26
      versus 0.11, P =.001) as well. Estimated cost per quality-adjusted life years for
      autologous blood donation for each category exceeded $1,000,000. CONCLUSION:
      Autologous blood donation is an expensive medical practice and does not guarantee
      that exposure to allogeneic blood will not occur. If pursued, it should be
      directed towards those who have a known malignancy or those for whom radical
      surgery is anticipated. Other methods of blood conservation may be safer and more
      cost-effective.

PMID- 11978285
TI  - Practice patterns among board-certified reproductive endocrinologists regarding
      high-order multiple gestations: a united states national survey.
AB  - OBJECTIVE: To assess current practice management, attitudes, and strategies of
      reproductive endocrinologists in the United States regarding high-order (at least
      three) multiple gestations. METHODS: Questionnaires were mailed to 768 board
      certified reproductive endocrinologists of whom 722 were eligible for the study.
      The questionnaires addressed topics such as practitioner demographics, management
      strategies, and attitudes regarding high-order multiple gestations. RESULTS: The
      survey response rate was 52%. Most physicians performed 100-300 cycles of each
      ovulation induction with intrauterine insemination and in vitro fertilization in
      1998 and 1999. The most commonly reported incidence of high-order multiple
      gestations resulting from each ovulation induction with intrauterine insemination
      and in vitro fertilization was 2-5% in 1998 and 1999. Strategies used to decrease
      the rate of high-order multiple gestations varied among practitioners. Informed
      consent regarding high-order multiple gestations was provided by 99.5% of
      practitioners. Information regarding selective reduction was provided by 98.3% of
      respondents. Over 90% of practitioners believed it is worthwhile to attempt to
      decrease the risk of high-order pregnancies at the risk of decreasing their
      group's overall pregnancy rates. CONCLUSION: Most reproductive endocrinologists
      reported concern over the rising risk of high-order multiple gestations resulting
      from therapies such as superovulation with intrauterine insemination or in vitro
      fertilization. However, the ways in which patients are counseled regarding such
      events, their sequelae, and methods to avoid them greatly differ among
      respondents. Given the inconsistent practice patterns, a multifaceted educational
      approach may provide an opportunity to reduce the incidence of high-order
      multiple gestations and their sequelae.

PMID- 11978288
TI  - Breast-feeding and its relation to smoking and mode of delivery.
AB  - OBJECTIVE: To examine the effects of cesarean and forceps or vacuum delivery and
      parental smoking habits on the initiation and duration of breast-feeding.
      METHODS: We conducted a prospective, population-based birth cohort study in 1997.
      Data were collected on breast-feeding history, household smoking habits, method
      of delivery, and other demographic, obstetric, behavioral, and potential
      confounding variables via a standardized self-administered questionnaire.
      Multivariable logistic regression was used to examine the association between
      method of birth (cesarean versus forceps or vacuum delivery versus normal vaginal
      birth) and either not initiating breast-feeding or doing so for less than 1
      month. Among women who breast-fed for 1 month or more, multivariable survival
      analysis was employed to study the relationship between method of delivery and
      breast-feeding duration. We repeated these analyses to examine the link between
      parental smoking habits and breast-feeding initiation and duration. RESULTS: A
      total of 7825 mother-infant pairs were followed up for 9 months. Cesarean
      delivery was a risk factor for not initiating breast-feeding, for breast-feeding
      less than 1 month, and remained a significant hazard against breast-feeding
      duration. Assisted delivery with forceps or vacuum, although not associated with
      breast-feeding initiation, was a significant risk against breast-feeding
      duration. Conversely, current parental smoking habits only affected breast
      feeding initiation but were unrelated to breast-feeding duration. CONCLUSION:
      This study indicates a possible effect of forceps or vacuum delivery on breast
      feeding and of cesarean on long-term breast-feeding duration. The findings
      provide additional evidence in support of the avoidance of unnecessary obstetric
      interventions.

PMID- 11978287
TI  - Isotretinoin for low-grade cervical dysplasia in human immunodeficiency virus
      infected women.
AB  - OBJECTIVE: To estimate the efficacy of isotretinoin for prevention of progression
      of low-grade squamous intraepithelial lesions (SIL) of the cervix to high-grade
      lesions or invasive cervical cancer; to estimate the regression rate of low-grade
      SIL with isotretinoin and the toxicity of isotretinoin in this setting; and to
      correlate serum CD4 levels with progression of low-grade SIL. METHODS: A
      randomized, phase III, observation-controlled, multicenter trial was performed in
      which 117 human immunodeficiency virus (HIV)-positive women with low-grade SIL of
      the cervix received either oral isotretinoin at 0.5 mg/kg per day for 6 months or
      observation. Papanicolaou smears and colposcopy/biopsy were done at regular
      intervals during follow-up. The primary endpoint was progression to high-grade
      SIL or cervical cancer. RESULTS: Twenty-one of 102 women (20.6%) completing
      follow-up experienced progression to high-grade SIL, 13 in the observation group
      and eight in the isotretinoin group. This difference was not significant (P
      =.29). No cases of invasive cancer were seen. Baseline CD4 levels were lower than
      anticipated (median 329 cells/mm(3)), but not associated with time to progression
      (P =.36). Most subjects (63 of 102, 61.7%) used highly active antiretroviral
      therapy. Subjects under age 30 were more likely to progress than those older than
      30 (P =.046). CONCLUSION: Isotretinoin was not associated with longer time to
      progression of low-grade SIL. This appears to be a chronic condition in HIV
      positive women, with a low risk of progression and significant rate of
      resolution. As in the general population, observation without excisional therapy
      may be appropriate for HIV-positive women with low-grade SIL.

PMID- 11978290
TI  - Weight gain in women of normal weight before pregnancy: complications in
      pregnancy or delivery and birth outcome.
AB  - OBJECTIVE: To investigate the relation between gestational weight gain in women
      of normal prepregnant weight and complications during pregnancy and delivery in a
      population with high gestational weight gain and birth weight. METHODS: Healthy
      women (n = 615) of normal weight before pregnancy (body mass index 19.5-25.5
      kg/m(2)) were randomly selected. Maternity records gave information on age,
      height, prepregnant weight, gestational weight gain, parity, smoking, gestational
      hypertension and diabetes, preeclampsia, delivery complications, and infants'
      birth size and health. RESULTS: The mean weight gain in pregnancy was 16.8 +/-
      4.9 kg (mean +/- standard deviation). A total of 26.4% of the women had
      complications, either in pregnancy (9.1%) or delivery (17.3%). Women gaining
      weight according to the recommendation of the Institute of Medicine (11.5-16.0
      kg) had lower frequency of pregnancy-delivery complications than women gaining
      more than 20.0 kg (P =.017), but did not differ significantly from those gaining
      16-20 kg (P >.05). When dividing weight gain in pregnancy into quintiles, a
      relative risk of 2.69 (95% confidence interval 1.01, 7.18, P =.048) was found for
      complications in pregnancy in the fourth quintile (17.9-20.8 kg), using the
      second quintile as reference (12.5-15.5 kg). The mean birth weight was 3778 +/-
      496 g. A low weight gain in pregnancy (less than 11.5 kg) was associated with an
      increased frequency of infants weighing less than 3500 g at birth (P <.01).
      CONCLUSION: A gestational weight gain of 11.5-16.0 kg (Institute of Medicine
      recommendation) for women of normal prepregnant weight is related to the lowest
      risk for pregnancy-delivery complications. In the population studied, the upper
      limit might be higher (up to 18 kg), and low weight gain should be avoided to
      optimize birth outcome.

PMID- 11978289
TI  - Detection of human parvovirus B19 infection in first-trimester fetal loss.
AB  - OBJECTIVE: To investigate the frequency of parvovirus B19 infection in first
      trimester fetal loss, as measured by B19 DNA polymerase chain reaction in
      placental tissue in a prospective descriptive study from a nonendemic area.
      METHODS: Placental tissues from first-trimester fetal losses were examined for
      presence of B19 DNA by polymerase chain reaction in a prospective study during 30
      months. For comparison, placental tissues from second-trimester fetal losses, as
      well as from full-term normal pregnancies, were also studied. RESULTS: B19 DNA
      was detected by polymerase chain reaction in one of 36 (3%) placental tissues
      from first-trimester fetal losses. In second-trimester fetal losses, eight of 64
      (12%) samples were B19 DNA positive. None of the 53 placental tissues from full
      term normal pregnancies were B19 DNA positive. In first-trimester fetal losses,
      maternal serum from the B19 DNA-positive sample was B19 immunoglobulin (Ig)G
      positive but B19 IgM negative. In second-trimester fetal losses, six of six
      tested B19 DNA-positive samples were both B19 IgG and IgM positive. CONCLUSION:
      The frequency of first-trimester fetal loss associated with parvovirus B19
      infection was low, 3%, during a nonepidemic period in Sweden, as measured by B19
      DNA-specific polymerase chain reaction in placental tissue.

PMID- 11978291
TI  - Maternal hemoglobin and risk of gestational diabetes mellitus in Chinese women.
AB  - OBJECTIVE: To examine the relationship between high maternal hemoglobin
      concentration at the initial antenatal visit and occurrence of gestational
      diabetes mellitus (GDM) in the third trimester in nonanemic women. METHODS: In a
      prospective observational study, 762 nondiabetic Chinese women with singleton
      pregnancies, whose initial visit hemoglobin concentration and mean cell volume
      were 10 g/dL or more and 80 fL or more, respectively, recruited at 28-30 weeks,
      had blood drawn for repeat measurement of hemoglobin concentration and iron
      parameters. These women were categorized by their initial visit hemoglobin
      concentration into quartiles, and the incidence of GDM was analyzed together with
      the maternal characteristics and iron status. RESULTS: The final study sample
      comprised 730 women. Compared with the rest, the group in the highest hemoglobin
      quartile (more than 13 g/dL) had a significantly higher incidence of GDM (18.7%
      versus 10.9%, P =.007), as well as greater age, weight, and serum ferritin and
      iron concentrations. Logistic regression was used to examine the effects of high
      body mass index (more than 25 kg/m(2)), advanced age (older than 34 years),
      parity of 1 or more, and hemoglobin in the highest quartile, on the incidence of
      GDM. Only advanced age (odds ratio 3.79, 95% confidence interval 2.33, 6.17) and
      hemoglobin in the highest quartile (odds ratio 1.73, 95% confidence interval
      1.08, 2.78) emerged to be significant factors. CONCLUSION: A high maternal
      hemoglobin (more than 13 g/dL) at the initial prenatal visit in Chinese women is
      an independent risk factor for GDM. This may reflect a better nutritional status
      in these women, as suggested by the increased iron status.

PMID- 11978292
TI  - Comparison of abortions induced by methotrexate or mifepristone followed by
      misoprostol.
AB  - OBJECTIVE: To compare the effectiveness, side effects, and acceptability of
      medical abortions induced by methotrexate and misoprostol with abortions induced
      by mifepristone and misoprostol. METHODS: This was a multicenter, randomized,
      nonblinded, controlled trial comparing 50 mg/m(2) of methotrexate followed 4-6
      days later by 800 microgram of vaginal misoprostol with 600 mg of oral
      mifepristone followed 36-48 hours by 400 microgram of oral misoprostol. RESULTS:
      There were 518 women in the methotrexate group and 524 women in the mifepristone
      group. In the methotrexate group, 21 women required suction curretage, two for
      continuing pregnancy, eight because of physician request (usually for excessive
      bleeding), and 11 because of patient request. In the mifepristone group, 22 women
      needed surgical termination, 17 because of physician request, and five because of
      patient request. By day 8, only 386 (74.5%) in the methotrexate group had
      completed the abortion compared with 474 (90.5%) in the mifepristone group, and
      the mean number of days from beginning to completion was 7.1 for methotrexate and
      3.3 for mifepristone (P </=.001). There were no differences in complications, and
      side effects were similar. Acceptance was slightly higher with mifepristone
      (88.0%) than with methotrexate (83.2%). CONCLUSION: Abortions induced with
      mifepristone completed faster than those induced with methotrexate, but the
      overall success rates, side effects, and complications were similar. Acceptance
      rates were slightly higher with mifepristone than methotrexate (P =.03).

PMID- 11978293
TI  - Body weight and risk of oral contraceptive failure.
AB  - OBJECTIVE: To examine the hypothesis that higher body weight increases the risk
      of oral contraceptive (OC) failure. METHODS: We conducted a retrospective cohort
      analysis of data from 755 randomly selected female enrollees of Group Health
      Cooperative of Puget Sound who completed an in-person interview and dietary
      questionnaire between 1990 and 1994 as control subjects for a case-control study
      of ovarian cysts. Among the 618 women who were OC ever-users, we used Cox
      proportional hazards regression models to estimate the relative risk (RR) of
      pregnancy while using OCs associated with body weight quartile. RESULTS: During
      2822 person-years of OC use, 106 confirmed pregnancies occurred (3.8 per 100
      person-years of exposure). After controlling for parity, women in the highest
      body weight quartile (70.5 kg or more) had a significantly increased risk of OC
      failure (RR 1.6, 95% confidence interval [CI] 1.1, 2.4) compared with women of
      lower weight. Higher elevations of risk associated with the highest weight
      quartile were seen among very low-dose OC users (RR 4.5, 95% CI 1.4, 14.4) and
      low-dose OC users (RR 2.6, 95% CI 1.2, 5.9), controlling for parity, race,
      religion, and menstrual cycle regularity. CONCLUSION: Our findings suggest that
      body habitus may affect metabolism sufficiently to compromise contraceptive
      effectiveness. Consideration of a woman's weight may be an important element of
      OC prescription.

PMID- 11978294
TI  - Career transitions:planning for alternative futures.
AB  - Transition to retirement is a necessary step for all physicians because of the
      physical and emotional changes that occur with the aging process, the physician's
      ethical responsibilities to patients, and at times, because there is a desire to
      pursue different goals. It is important to begin to plan for this transition
      early in one's career so that some planning for postretirement vocation and
      avocation can be made and financial concerns can be addressed. A recent ACOG
      survey of 1000 Fellows ages 40-60 demonstrates that this planning is not
      occurring universally and the assistance of Fellows in preparation for this
      transition is now becoming an ACOG initiative.

PMID- 11978295
TI  - What's a smart woman like you doing at home?

PMID- 11978296
TI  - The economic value of medical research: is it worth the investment?
AB  - OBJECTIVE: To provide a brief commentary regarding the economic evaluation of
      medical research by summarizing a recent report from the Mary Woodard Lasker
      Charitable Trust. METHODS: A review of the report Exceptional Returns: The
      Economic Value of America's Investment in Medical Research was conducted. In this
      report, nine economists translated the accomplishments of medical research into
      dollars by placing a monetary value on better health and longer life. This
      manuscript focuses on implications of this report to women's health research.
      RESULTS: After first isolating the impact of medical research from other gains
      unrelated to research and development, the increase in life expectancy due to
      advances in health during the 1970s and 1980s were worth $57 trillion to
      Americans. Gains associated with prevention and treatment of cardiovascular
      disease alone totaled $31 trillion. CONCLUSION: Our nation's contribution into
      medical research provides a very high "return on investment." The likely returns
      from research are so favorable that the payoff from any "portfolio" of research
      investments would be enormous.

PMID- 11978298
TI  - Drug interactions between oral contraceptives and antibiotics.

PMID- 11978299
TI  - Maternity leave: existing policies in obstetrics and gynecology residency
      programs.

PMID- 11978300
TI  - Hepatoxicity with antiretroviral treatment of pregnant women.

PMID- 11978303
TI  - ACOG Committee Opinion. Follow-up of abnormal screening mammography, number 272,
      May 2002.
AB  - Screening mammography facilitates the early diagnosis of breast carcinoma in
      women. Timely follow-up can optimize the diagnosis and treatment of women with
      abnormal screening test results. When test results reveal that additional studies
      are needed, no barriers should prohibit testing during the screening mammography
      visit.

PMID- 11978302
TI  - ACOG practice bulletin. Diagnosis and treatment of cervical carcinomas, number
      35, May 2002.
AB  - Invasive cervical carcinoma, once the most common reporductive-tract cancer in
      the United States, has recently fallen to the rank of third most common.
      Globally, cervical cancer is a major health problem, with a yearly incidence of
      371,000 cases and an annual death rate of 190,000 (1). The International
      Federation of Gynecology and Obstetrics (FIGO) recently revised its staging
      criteria. In addition, new evidence has documented conclusively that survival
      rates for women with cervical cancer improve when radiotherapy is combined with
      cisplatin-based chemotherapy. This document will describe staging criteria and
      treatment for cervical carcinoma. For practical purposes, it will focus on the
      squamous and adenocarcinoma histologies only.

PMID- 11978304
TI  - ACOG committee opnion: antenatal corticosteroid therapy for fetal maturation.
AB  - The National Institute of Child Health and Human Development and the Office of
      Medical Applications of Research of the National Institutes of Health convened
      consensus conference in 1194 and 2000 that recommended giving a single course of
      corticosteriods to all pregnant women between 24 and 34 weeks of gestation who
      are at risk of preterm delivery within 7 days. Because of insufficient scientific
      evidence, the consensus panel also recommended that repeat corticosteroid
      courses, including so-called "rescue therapy," should not be routinely used but
      should be reserved for women enrolled in clinical trials. Betamethasone and
      dexamethasone have been most widely studied and have generally been the preferred
      corticosteroids for antenatal treatment to accelerate fetal organ maturation. The
      American College of Obstetricians and Gynecologists' Committee on Obstetric
      Practice supports the conclusions of the consensus conferences.

PMID- 11978326
TI  - How to make global trade diminish poverty.

PMID- 11978327
TI  - Ghrelin gets hungry.

PMID- 11978328
TI  - Value of FDG-PET scanning in management of lung cancer.

PMID- 11978329
TI  - Evolution of the implantable cardioverter defibrillator.

PMID- 11978330
TI  - Market forces in public health.

PMID- 11978331
TI  - Science and myth.

PMID- 11978332
TI  - Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum
      malaria in African children: a randomised, multicentre trial.
AB  - BACKGROUND: Increasing drug resistance limits the choice of efficacious
      chemotherapy against Plasmodium falciparum malaria in Africa. Amodiaquine still
      retains efficacy against P falciparum in many African countries. We assessed the
      safety, treatment efficacy, and effect on gametocyte carriage of adding
      artesunate to amodiaquine in three randomised trials in Kenya, Senegal, and
      Gabon. METHODS: We enrolled 941 children (400 in Kenya, 321 in Senegal, and 220
      in Gabon) who were 10 years or older and who had uncomplicated P falciparum
      malaria. Patients were randomly assigned amodiaquine (10 mg/kg per day for 3
      days) plus artesunate (4 mg/kg per day for 3 days) or amodiaquine (as above) and
      placebo (for 3 days). The primary endpoints were parasitological cure rates at
      days 14 and 28. Analysis was by intention to treat and by an evaluability method.
      FINDINGS: Both regimens were well tolerated. Six patients in the amodiaquine
      artesunate group and five in the amodiaquine group developed early, drug-induced
      vomiting, necessitating alternative treatment. By intention-to-treat analysis,
      the day-14 cure rates for amodiaquine-artesunate versus amodiaquine were: 175/192
      (91%) versus 140/188 (74%) in Kenya (D=16.7% [95% CI 9.3-24.1], p<0.0001),
      148/160 (93%) versus 147/157 (94%) in Senegal (-1.1% [-6.7 to 4.5], p=0.7), and
      92/94 (98%) versus 86/96 (90%) in Gabon (8.3% [1.5-15.1], p=0.02). The
      corresponding rates for day 28 were: 123/180 (68%) versus 75/183 (41%) in Kenya
      (27.3% [17.5-37.2], p<0.0001), 130/159 (82%) versus 123/156 (79%) in Senegal
      (2.9% [-5.9 to 11.7], p=0.5), and 80/94 (85%) versus 70/98 (71%) in Gabon (13.7%
      [2.2-25.2], p=0.02). Similar rates were obtained by evaluability analysis.
      INTERPRETATION: The combination of artesunate and amodiaquine improved treatment
      efficacy in Gabon and Kenya, and was equivalent in Senegal. Amodiaquine
      artesunate is a potential combination for use in Africa. Further investigations
      to assess the potential effect on the evolution of drug resistance, disease
      transmission, and safety of amodiaquine-artesunate are warranted.

PMID- 11978333
TI  - Clinical picture: scapular calcinosis.

PMID- 11978334
TI  - Causes of prescribing errors in hospital inpatients: a prospective study.
AB  - BACKGROUND: To prevent errors made during the prescription of drugs, we need to
      know why they arise. Theories of human error used to understand the causes of
      mistakes made in high-risk industries are being used in health-care. They have
      not, however, been applied to prescribing errors, which are a great cause of
      patient harm. Our aim was to use this approach to investigate the causes of such
      errors. METHODS: Pharmacists at a UK teaching hospital prospectively identified
      88 potentially serious prescribing errors. We interviewed the prescribers who
      made 44 of these, and analysed our findings with human error theory. FINDINGS:
      Our results suggest that most mistakes were made because of slips in attention,
      or because prescribers did not apply relevant rules. Doctors identified many risk
      factors-work environment, workload, whether or not they were prescribing for
      their own patient, communication within their team, physical and mental well
      being, and lack of knowledge. Organisational factors were also identified, and
      included inadequate training, low perceived importance of prescribing, a
      hierarchical medical team, and an absence of self-awareness of errors.
      INTERPRETATION: To reduce prescribing errors, hospitals should train junior
      doctors in the principles of drug dosing before they start prescribing, and
      enforce good practice in documentation. They should also create a culture in
      which prescription writing is seen as important, and formally review
      interventions made by pharmacists, locum arrangements, and the workload of junior
      doctors, and make doctors aware of situations in which they are likely to commit
      errors.

PMID- 11978335
TI  - Long-term effectiveness and safety of pravastatin in 9014 patients with coronary
      heart disease and average cholesterol concentrations: the LIPID trial follow-up.
AB  - BACKGROUND: The Long-term Intervention with Pravastatin in Ischaemic Disease
      (LIPID) study showed that pravastatin therapy over 6 years reduced mortality and
      cardiovascular events in patients with previous acute coronary syndromes and
      average cholesterol concentrations. We assessed the longer-term effects of
      initial treatment with pravastatin on further cardiovascular events and mortality
      over a total follow-up period of 8 years. METHODS: In the main trial, 9014
      patients with previous myocardial infarction or unstable angina and a baseline
      plasma cholesterol concentration of 4.0-7.0 mmol/L were randomly assigned
      pravastatin 40 mg daily or placebo and followed up for 6 years. Subsequently, all
      patients were offered open-label pravastatin for 2 more years. Major
      cardiovascular events and adverse events were compared according to initial
      treatment assignment. FINDINGS: 7680 (97% of those still alive) had 2 years of
      extended follow-up. 3766 (86%) of those assigned placebo and 3914 (88%) assigned
      pravastatin agreed to take open-label pravastatin. During this period, patients
      originally assigned pravastatin had almost identical cholesterol concentrations
      to those assigned placebo, but a lower risk of death from all causes (219 [5.6%]
      vs 255 [6.8%], p=0.029), coronary heart disease (CHD) death (108 [2.8%] vs 137
      [3.6%], p=0.026), and CHD death or non-fatal myocardial infarction (176 [4.5%] vs
      196 [5.2%], p=0.08). Over the total 8-year period, all-cause mortality was 888
      (19.7%) in the group originally assigned placebo and 717 (15.9%) in the group
      originally assigned pravastatin, CHD mortality was 510 (11.3%) versus 395 (8.8%),
      myocardial infarction was 570 (12.7%) versus 435 (9.6%; each p < 0.0001), and
      stroke was 272 (6.0%) versus 224 (5.0%; p=0.015). Stronger evidence of separate
      treatment benefits than in the main trial was seen in important prespecified
      subgroups (women, patients aged > or = 70 years, and those with total cholesterol
      < 5.5 mmol/L). Pravastatin had no significant adverse effects. INTERPRETATION:
      The evidence of sustained treatment benefits and safety of long-term pravastatin
      treatment reinforces the importance of long-term cholesterol-lowering treatment
      for almost all patients with previous CHD events.

PMID- 11978336
TI  - Effectiveness of positron emission tomography in the preoperative assessment of
      patients with suspected non-small-cell lung cancer: the PLUS multicentre
      randomised trial.
AB  - BACKGROUND: Up to 50% of curative surgery for suspected non-small-cell lung
      cancer is unsuccessful. Accuracy of positron emission tomography (PET) with 18
      fluorodeoxyglucose (18FDG) is thought to be better than conventional staging for
      diagnosis of this malignancy. Up to now however, there has been no evidence that
      PET leads to improved management of patients in routine clinical practice. We did
      a randomised controlled trial in patients with suspected non-small-cell lung
      cancer, who were scheduled for surgery after conventional workup, to test whether
      PET with 18FDG reduces number of futile thoracotomies. METHODS: Before surgery
      (mediastinoscopy or thoracotomy), 188 patients from nine hospitals were randomly
      assigned to either conventional workup (CWU) or conventional workup and PET
      (CWU+PET). Patients were followed up for 1 year. Thoracotomy was regarded as
      futile if the patient had benign disease, explorative thoracotomy, pathological
      stage IIIA-N2/IIIB, or postoperative relapse or death within 12 months of
      randomisation. The primary outcome measure was futile thoracotomy. Analysis was
      by intention to treat. FINDINGS: 96 patients were randomly assigned CWU and 92
      CWU+PET. Two patients in the CWU+PET group did not undergo PET. 18 patients in
      the CWU group and 32 in the CWU+PET group did not have thoracotomy. In the CWU
      group, 39 (41%) patients had a futile thoracotomy, compared with 19 (21%) in the
      CWU+PET group (relative reduction 51%, 95% CI 32-80%; p=0.003). INTERPRETATION:
      Addition of PET to conventional workup prevented unnecessary surgery in one out
      of five patients with suspected non-small-cell lung cancer.

PMID- 11978338
TI  - Exertional haematuria.

PMID- 11978337
TI  - BCG-induced increase in interferon-gamma response to mycobacterial antigens and
      efficacy of BCG vaccination in Malawi and the UK: two randomised controlled
      studies.
AB  - BACKGROUND: The efficacy of BCG vaccines against pulmonary tuberculosis varies
      between populations, showing no protection in Malawi but 50-80% protection in the
      UK. To investigate the mechanism underlying these differences, randomised
      controlled studies were set up to measure vaccine-induced immune responsiveness
      to mycobacterial antigens in both populations. METHODS: 483 adolescents and young
      adults in Malawi and 180 adolescents in the UK were tested for interferon-gamma
      (IFN-gamma) response to M tuberculosis purified protein derivative (PPD) in a
      whole blood assay, and for delayed type hypersensitivity (DTH) skin test response
      to tuberculin PPD, before and 1 year after receiving BCG (Glaxo 1077) vaccination
      or placebo or no vaccine. FINDINGS: The percentages of the randomised individuals
      who showed IFN-gamma and DTH responses were higher in Malawi than in the UK pre
      vaccination-ie, 61% (331/546) versus 22% (47/213) for IFN-gamma and 46% (236/517)
      versus 13% (27/211) for DTH. IFN-gamma responses increased more in the UK than in
      Malawi, with 83% (101/122) and 78% (251/321) respectively of the vaccinated
      groups responding, with similar distributions in the two populations 1 year post
      vaccination. The DTH response increased following vaccination in both locations,
      but to a greater extent in the UK than Malawi. The IFN-gamma and DTH responses
      were strongly associated, except among vaccinees in Malawi. INTERPRETATION: The
      magnitude of the BCG-attributable increase in IFN-gamma responsiveness to M
      tuberculosis PPD, from before to 1 year post-vaccination, correlates better with
      the known levels of protection induced by immunisation with BCG than does the
      absolute value of the IFN-gamma or DTH response after vaccination. It is likely
      that differential sensitisation due to exposure to environmental mycobacteria is
      the most important determinant of the observed differences in protection by BCG
      between populations.

PMID- 11978339
TI  - Hydronephrosis associated with retroperitoneal fibrosis and sclerosing
      pancreatitis.
AB  - Sclerosing pancreatitis is associated with raised concentrations of IgG4. We
      treated 22 patients with sclerosing pancreatitis, and identified and followed-up
      three with concomitant hydronephrosis caused by ureteral mass, later diagnosed as
      retroperitoneal fibrosis. We histologically examined the ureteral and pancreatic
      lesions of these patients and noted abundant infiltration of IgG4-bearing plasma
      cells in both tissues. Treatment with corticosteroids lowered serum
      concentrations of IgG4. IgG4 might also have a pathological role in a systemic
      fibrosing process that includes pancreatic and retroperitoneal lesions.

PMID- 11978340
TI  - Mechanism of protection induced by vitamin A in falciparum malaria.
AB  - Supplementation with vitamin A potentiates host resistance to malaria, however,
      the underlying mechanism is unknown. We tested the effects of 9-cis-retinoic
      acid, a metabolite of vitamin A, on CD36 expression, non-opsonic phagocytic
      clearance of parasitised erythrocytes, and TNFalpha production in human monocytes
      and macrophages. We found reduced secretion of TNFalpha, upregulated CD36
      expression, and increased phagocytosis of Plasmodium falciparum-parasitised
      erythrocytes. Increased parasite clearance and reduced proinflammatory cytokine
      responses to infection might partly explain the beneficial effects of
      supplementation with vitamin A in malaria.

PMID- 11978341
TI  - Audiovisual documentation of oral consent: a new method of informed consent for
      illiterate populations.
AB  - Informed consent is a legal and ethical requirement of most research in human
      beings, but obtaining proof of consent in illiterate populations can prove
      problematic. We used audiovisual documentation of oral consent (video and
      audiotape recording and photography), a new method of informed consent designed
      for illiterate populations, in the Guarani Indians Project, a genetic study in
      the Paraguayan Guarani Indians. We obtained consent from 42 of about 100
      potential participants. We believe that our procedure allowed more than half the
      potential participants to exercise their freedom of refusal. We propose to
      include this new method as a standard procedure for clinical research in
      illiterate populations as an alternative to written and signed consent.

PMID- 11978342
TI  - Parental periconceptional smoking and male: female ratio of newborn infants.
AB  - We assessed whether the smoking habits of parents around the time of conception
      affects the likelihood of the offspring being male or female. We found that the
      offspring sex ratio (male to female) was lower when either one or both of the
      parents smoked more than 20 cigarettes per day compared with couples in which
      neither of the parents smoked. We found the lowest sex ratio among children whose
      mothers and fathers both smoked more than 20 cigarettes per day (p<0.0001).
      Parental periconceptional smoking might be a contributing factor to a lower male
      to female sex ratio of offspring.

PMID- 11978343
TI  - Srebrenica tragedy forces Dutch government to resign.

PMID- 11978344
TI  - Why do COX-2 inhibitors increase risk of cardiovascular events?

PMID- 11978345
TI  - Clues to mechanism of Pseudomonas resistance in cystic fibrosis.

PMID- 11978346
TI  - Diabetic patients can safely undergo vascular surgery, claim US researchers.

PMID- 11978347
TI  - A new technique for identifying risk for type 2 diabetes?

PMID- 11978348
TI  - Obesity rising to alarming levels around the world.

PMID- 11978349
TI  - Plans to fund increased expenditure for NHS.

PMID- 11978351
TI  - Indian groups demand ban on asbestos.

PMID- 11978352
TI  - "Urgent global response" needed to vaccinate the world's children.

PMID- 11978353
TI  - Spain launches a very modern model of research integration.

PMID- 11978354
TI  - Advocacy group urges safe injection facilities for Canada's addicts.

PMID- 11978355
TI  - South Africa's apartheid era doctor found not guilty.

PMID- 11978356
TI  - Child prostitution: global health burden, research needs, and interventions.
AB  - Child prostitution is a significant global problem that has yet to receive
      appropriate medical and public health attention. Worldwide, an estimated 1
      million children are forced into prostitution every year and the total number of
      prostituted children could be as high as 10 million. Inadequate data exist on the
      health problems faced by prostituted children, who are at high risk of infectious
      disease, pregnancy, mental illness, substance abuse, and violence. Child
      prostitution, like other forms of child sexual abuse, is not only a cause of
      death and high morbidity in millions of children, but also a gross violation of
      their rights and dignity. In this article we estimate morbidity and mortality
      among prostituted children, and propose research strategies and interventions to
      mitigate such health consequences. Our estimates underscore the need for health
      professionals to collaborate with individuals and organisations that provide
      direct services to prostituted children. Health professionals can help efforts to
      prevent child prostitution through identifying contributing factors, recording
      the magnitude and health effects of the problem, and assisting children who have
      escaped prostitution. They can also help governments, UN agencies, and non
      governmental organisations (NGOs) to implement policies, laws, and programmes to
      prevent child prostitution and mitigate its effects on children's health.

PMID- 11978357
TI  - Uses of error: early and late.

PMID- 11978358
TI  - Intimate partner violence: causes and prevention.
AB  - Unlike many health problems, there are few social and demographic characteristics
      that define risk groups for intimate partner violence. Poverty is the exception
      and increases risk through effects on conflict, women's power, and male identity.
      Violence is used as a strategy in conflict. Relationships full of conflict, and
      especially those in which conflicts occur about finances, jealousy, and women's
      gender role transgressions are more violent than peaceful relationships. Heavy
      alcohol consumption also increases risk of violence. Women who are more empowered
      educationally, economically, and socially are most protected, but below this high
      level the relation between empowerment and risk of violence is non-linear.
      Violence is frequently used to resolve a crisis of male identity, at times caused
      by poverty or an inability to control women. Risk of violence is greatest in
      societies where the use of violence in many situations is a socially-accepted
      norm. Primary preventive interventions should focus on improving the status of
      women and reducing norms of violence, poverty, and alcohol consumption.

PMID- 11978360
TI  - Insurance agreement to facilitate genetic testing.

PMID- 11978359
TI  - Screening for and treating left-ventricular abnormalities in diabetes mellitus: a
      new way of reducing cardiac deaths.

PMID- 11978361
TI  - Treatment of insomnia.

PMID- 11978362
TI  - Treatment for insomnia.

PMID- 11978363
TI  - Treatment for insomnia.

PMID- 11978365
TI  - Appropriateness ratings.

PMID- 11978366
TI  - Appropriateness ratings.

PMID- 11978368
TI  - MRI, monosclerosis, and multiple sclerosis.

PMID- 11978369
TI  - Irritable bowel syndrome and coeliac disease.

PMID- 11978370
TI  - Effect of polychlorinated biphenyls on psychodevelopment.

PMID- 11978371
TI  - Effect of polychlorinated biphenyls on psychodevelopment.

PMID- 11978373
TI  - Drug advertisements in less-developed countries.

PMID- 11978374
TI  - Does it matter how epilepsy is considered and classified?

PMID- 11978375
TI  - Coagulation, angiogenesis, and venous thromboembolism in cancer.

PMID- 11978376
TI  - Doctors and torture after Sept 11.

PMID- 11978388
TI  - The developmental segregation of posterior crista and saccular vestibular fibers
      in mice: a carbocyanine tracer study using confocal microscopy.
AB  - The developmental segregation of gravistatic input mediated by saccular fibers
      and of angular acceleration input mediated by posterior crista (PC) fibers was
      analyzed for the first time in a developing mammal using carbocyanine dye tracing
      in fixed tissue. The data reveal a more extensive projection of either endorgan
      in 7-day-old mice (P7) than has previously been reported in adult mammals. While
      we confirm and extend many previous findings, we also describe a novel
      segregation of saccular and posterior crista fibers in the anterior half of the
      medial vestibular nucleus (Mv) not reported before. Our developmental analysis
      shows a progressive segregation of posterior crista and saccular fibers to their
      respective discrete projection areas between embryonic day 15 (E15) and birth
      (P0). Retention of overlap in young adult animals appears to reflect the early
      embryonic overlap found in most areas. The vestibular projection does not show a
      topological projection as has been described in many other sensory systems. We
      propose that the unique projection features of the vestibular endorgans may
      relate to the transformation of vestibular signals into a motor output in the
      three neuron reflex arc of the VOR, of which the primary vestibular projection
      constitutes the first leg.

PMID- 11978389
TI  - Differences in neuronal differentiation between the transient cranial (Frorieps')
      and normal dorsal root ganglia.
AB  - The Frorieps' ganglia are dorsal root ganglia (DRG) that form, grow slowly
      compared to normal DRG, and then degenerate during normal embryonic development
      of amniotes. Their fate has been shown to be regulated by the Hox family and
      other genes involved in pattern formation, and by the mesodermal microenvironment
      of the cranial somites in which they develop. Neurons are known to differentiate
      within the Frorieps' DRG in the course of their short life span. In this study,
      we compared several aspects of neural differentiation between the longest-lived
      Frorieps' ganglia, DRG2, and normal trunk DRG in chick embryos. The expression of
      transcription factor Islet-1 and the RNA-binding protein Hu differ between normal
      and Frorieps' DRG at St. 23 (embryonic day 4). Islet-1 is expressed in a higher
      proportion of cells in DRG2 than DRG5, suggesting that cells in DRG2
      differentiate more rapidly into neurons than in normal DRG. This molecular
      difference appears at the same developmental stage as overt morphological
      differences between DRG2 and normal DRG. Other LIM-homeobox proteins (Lim-1, -2
      and -3 and Islet-2) are not expressed either in normal or Frorieps' DRG at early
      stages of development. Somite-grafting experiments reveal that the increased
      proportion of Isl-1(+) in DRG2 is due to the special microenvironment of the
      cranial somites. In contrast to Islet-1, the Hu antigen is expressed in a
      slightly lower proportion of cells in DRG2 at St. 23. At St. 28, there is a
      significant population of neurons in DRG2 that are Isl-1(+)/Hu(-). Since Islet-1
      is normally expressed before Hu in DRG cells, it is possible that the reduced
      growth rate of the DRG2 ganglion may partially result from the inability of
      precociously differentiating Islet-1(+) neurons to further mature, as reflected
      by Hu antigen expression. In contrast to the neuronal markers examined, the
      satellite cell marker 7B3 is expressed at similar levels in DRG2 and DRG5.

PMID- 11978390
TI  - EphA4 is not required for Purkinje cell compartmentation.
AB  - The Purkinje cells of both the adult and the developing cerebellar cortex are
      organized into parasagittal stripes or 'segments' expressing a variety of
      biochemical markers. We show that in the developing mouse cerebellar cortex,
      members of the Eph receptor gene family are expressed in mediolaterally
      alternating Purkinje cell segments. Since members of the Eph receptors family
      have been shown to play a role in hindbrain segmentation and boundary formation
      (Philos. Trans. R. Soc. Lond. B: Biol. Sci. 355 (2000) 993), we analyzed the
      effect of a null mutation of the EphA4 gene on Purkinje cell compartmentation.
      Using well characterized markers of Purkinje cell compartmentation in both the
      developing and the adult cerebellum, we observed no significant alteration in the
      banding pattern of these markers between the EphA4 knockout mice and their wild
      type controls. The ribboned pattern of migrating granule cells in the developing
      cerebellum also appears unaltered. The expression of other members of this gene
      family, including ephrin-B2, EphA2, and ephrin-A1, in a compartmentalized pattern
      within the Purkinje cell layer suggests a possible redundancy and/or a
      compensation of EphA4 function in the segmental patterning of cerebellar Purkinje
      cells.

PMID- 11978391
TI  - Calretinin and FMRFamide immunoreactivity in the nervus terminalis of prenatal
      tree shrews (Tupaia belangeri).
AB  - The distribution and development of FMRFamide- and calretinin-immunoreactive
      neurons were investigated in the nervus terminalis of prenatal tree shrews from
      gestation day 19 onwards. The first FMRFamide-immunoreactive cells were observed
      medially in the olfactory epithelium on gestation day 20. From gestation day 23
      onwards, the migrating nervus terminalis ganglion cells showed FMRFamide
      calretinin immunoreactivity. The distribution pattern of FMRFamide- and
      calretinin-immunoreactive cells was similar along the migratory route and in the
      ganglion of the terminal nerve. However, most probably calretinin and FMRFamide
      were expressed in separate neuronal populations. For the first time in a mammal,
      FMRFamide and calretinin are reported to occur in the migrating perikarya and
      neuronal processes of the nervus terminalis during prenatal development. The
      results suggest (i) an early activation of the rostral FMRFamide-immunoreactive
      migratory stream comparable to that described for the GnRH-immunoreactive part of
      the terminal nerve in other mammals and possibly (ii) an involvement of
      calretinin in mechanisms of cell migration and outgrowth of neuronal processes in
      the terminal nerve during the studied period.

PMID- 11978393
TI  - Inhibition of neurite outgrowth by reduced level of NDRG4 protein in antisense
      transfected PC12 cells.
AB  - NDRG4, a member of the new NDRG gene family, was originally cloned as a gene that
      was expressed predominantly in the early postnatal rat brain. To determine
      whether the NDRG4 protein contributes to differentiation of neural cells, the
      effect of lowering the cellular NDRG4 protein level on the nerve growth factor
      (NGF)-induced neurite formations and transcription factor activations in PC12
      cells was examined. An antisense construct of rat NDRG4 cDNA was made and
      transfected to PC12 cells, which constitutively express a basal level of the
      NDRG4 protein. Of the stably transfected antisense cell clones that expressed
      exogenous NDRG4 antisense RNA, six clones showed reduced levels of the NDRG4
      protein, but unexpectedly two clones showed quite higher levels of NDRG4 protein
      than the control cells. The clones having decreased levels of the NDRG4 protein
      extended shorter neurites than control cells in response to NGF or dibutyryl
      cAMP. In contrast, the NDRG4 protein-highly expressing clones did not show
      suppressed neurite outgrowth induced by NGF. NGF-mediated activation of the
      transcription factor AP-1 was found to be suppressed in the NDRG4 protein
      diminished clone and enhanced in the NDRG4 protein-upregulated clone as compared
      with those in the control cells. These results suggest that NDRG4 plays a role in
      neurite outgrowth and has an influence on an NGF-stimulated AP-1 activation by an
      undefined mechanism in PC12 cells.

PMID- 11978392
TI  - Molecular characterization of NDRG4/Bdm1 protein isoforms that are differentially
      regulated during rat brain development.
AB  - We previously reported the identification of a novel gene, Bdm1/NDRG4, that was
      expressed predominantly in the postnatal rat brain and might possibly play a role
      in this process. We describe here the characterization of a NDRG4 protein in a
      developing and maturing rat brain. Antibody raised against glutathione S
      transferase (GST)-NDRG4 fusion protein recognized four protein species of 38, 39,
      41, and 45 kDa on Western blotting of proteins from differently staged rat
      brains. The 38-kDa form was revealed after birth, and the amount of this species
      peaked on postnatal day 15. The 39-kDa form became detectable after postnatal
      week 6. The 41-kDa form appeared late in embryogenesis, increased by postnatal
      day 15, and disappeared at postnatal week 6. The 45-kDa form was abundant during
      the late embryonic period and slightly decreased after birth. Subcellular
      fractionation of cerebra indicated that the NDRG4 protein was distributed mainly
      in the mitochondria and endoplasmic reticulum (ER). Detergent solubility assays
      and protease susceptibility demonstrated that in the ER NDRG4 protein is membrane
      associated and luminally oriented. The 45-kDa isoform was induced during NGF
      mediated neuronal differentiation of PC12 cells, but not by tunicamycin which
      causes ER stress. Differential expressions of NDRG4 protein isoforms may be a
      mechanism for modifying the NDRG4 function and for the formation of a functioning
      nervous system.

PMID- 11978394
TI  - Taste development: differential growth rates of tongue regions in humans.
AB  - There is a paucity of information about the anatomical and functional development
      of the human gustatory system. Although the anatomical development of the taste
      sensitive fungiform, circumvallate and foliate papillae in the respective
      anterior, posterior and latero-posterior regions of the dorsal surface of the
      tongue has been well documented in the fetus, there is limited information about
      how these regions grow and when they exhibit adult function. The present study is
      concerned with determining when the growth of one of these taste-sensitive
      regions becomes adult in size, namely, the anterior region, and how this growth
      compares with that of the remaining posterior region. Two-hundred and thirty-two
      living subjects aged between 4 and 32 years participated. Following the
      identification and marking of a series of landmarks on the dorsal surface of the
      tongue with blue food dye, five measurements of the width and length of various
      parts of the tongue allowed calculation of the growth of the anterior and
      posterior regions. The results indicate that the fungiform papillae-rich anterior
      region attains adult-size by 8-10 years of age whilst the posterior region
      continues to grow until 15-16 years. Interestingly, this early development is not
      matched by achievement of adult function [Dev. Brain Res. 82 (1994) 286] or adult
      size papillae or taste pores [Dev. Brain Res., submitted]. Finally, the findings
      of the present study will allow studies of the development of taste function in
      humans to be conducted using equivalent tongue areas in subjects of different
      ages.

PMID- 11978395
TI  - Age-related distribution of c-fos expression in the striatum of CD-1 mice after
      acute methylphenidate administration.
AB  - Ritalin (methylphenidate hydrochloride, MPH) is the drug of choice for the
      treatment of attention deficit hyperactivity disorder. Previous research has
      shown that MPH administration affects the adult brain in a manner different from
      the young brain. In the current study, we set out to determine the target brain
      regions of acutely administered MPH at different stages of development. On
      postnatal days 3, 7, 11, 24, and 45, mice were treated with a single injection
      (s.c.) of saline, 5 or 20 mg/kg of MPH, and sacrificed 1 h later. Localization of
      c-fos expression was determined by immunocytochemistry. Compared to saline
      treated controls, mice treated with the high dose of MPH (20 mg/kg) showed dense
      Fos-immunoreactivity (Fos-IR) in the striatum. In most cases the low dose of MPH
      (5 mg/kg) produced only weak c-fos expression that was nearly indistinguishable
      from saline-treated controls. At PND 3 and 7, Fos-IR was localized in patches in
      the striatum. This patchy distribution of c-fos positive cells began to decline
      by PND 11 and was absent in PND 45 mice, with Fos-IR showing a scattered
      distribution throughout the striatum. The results of this study indicate that MPH
      induces the expression of c-fos in the same brain regions as cocaine and
      amphetamine, and that this expression is distributed differentially according to
      the age of the mouse.

PMID- 11978396
TI  - Muscarinic receptor protein expression in the ocular tissues of the chick during
      normal and myopic eye development.
AB  - Muscarinic receptor signalling has been implicated in both the embryonic and
      postnatal development of ocular structures as well as in myopic eye growth. A
      radioligand binding assay was used to determine whether changes in muscarinic
      receptor density and/or affinity occurred in the chick retina, choroid and sclera
      during early post-hatching development or with the induction of myopia. Specific
      receptor binding sites were saturable with increasing concentrations of the
      muscarinic receptor ligand [3H]N-methyl-scopolamine in the retina and choroid but
      not in the sclera. In normal eyes, binding density in the retina was not altered
      from age P5 to P10 (447+/-14 vs. 411+/-13 fmol/mg of protein, P=0.07). However,
      in the choroid, the number of receptor binding sites significantly increased
      between P5 and P10 (637+/-39 vs. 1125+/-121 fmol/mg of protein, P<0.01). Binding
      affinity (K(D)) was not altered with age in either the retina or choroid. Myopia
      was induced in chicks by deprivation of form vision, using translucent diffusers,
      from age P3. Despite the induction of significant degrees of ocular elongation
      and myopia at P5 (-8.7+/-0.3 D, P<0.01) and P10 (-22.5+/-1.3 D, P<0.01), neither
      muscarinic receptor density nor affinity were altered in the retina or choroid of
      myopic eyes. These findings indicate that regulation of muscarinic receptor
      numbers in the chick choroid is occurring in normal post-hatching development of
      this tissue. However, myopic eye enlargement was not associated with changes in
      muscarinic receptor protein expression in the chick retina and choroid.

PMID- 11978397
TI  - Effect of endogenous beta-hydroxybutyrate on brain glucose metabolism in fetuses
      of diabetic rabbits, studied by (13)C magnetic resonance spectroscopy.
AB  - The aim of our research was to uncover perturbations in in-utero fetal cerebral
      metabolism resulting from hyperglycemia and hyperketonemia, which occur during
      maternal diabetes. Therefore, we examined the effects of glucose overload and
      hyperketonemia on glucose metabolism in the diabetic fetal brain; more
      specifically, the effect of diabetes on the glucose flux via pyruvate
      dehydrogenase (PDH) and pyruvate carboxylase (PC) and subsequent metabolism in
      the fetal cerebral tricarboxylic acid (TCA) cycle were examined, as well as the
      effect of diabetes on energy fuel utilization in the neurons and glia. Diabetes
      was induced in pregnant rabbits, and towards term, [U-(13)C(6)]glucose was
      infused into maternal circulation, and [(13)C]glucose metabolites were
      subsequently studied in fetal brain extracts by (13)C MRS isotopomer analysis.
      Significantly elevated maternal and fetal plasma glucose levels (three- and up to
      fivefold, respectively) and fetal brain glucose levels (up to eightfold)
      accompanied by an increase of beta-hydroxybutyrate (beta-HBA) levels
      (approximately 20-fold) were found in the hyperketonemic diabetic animals,
      whereas fetal cerebral lactate levels were decreased. Alterations in the (13)C
      labeling patterns, mainly of glutamine, led us to suggest that the entry of beta
      HBA-derived acetyl-CoA inhibits formation and entry of labeled glucose-derived
      acetyl-CoA into the TCA cycle, mainly in glia. Accumulation of glucose and the
      decrease in lactate levels in the fetal brain are most likely the result of an
      inhibitory effect of beta-HBA on glycolysis. In addition, loss of (13)C
      enrichment of TCA cycle intermediates and products, glutamate and glutamine, in
      the hyperketonemic diabetic fetal brain may be attributed to the effect of beta
      HBA fuel utilization by the fetal brain.

PMID- 11978398
TI  - Lack of cell loss following recurrent neonatal seizures.
AB  - In the neonatal rat recurrent seizures have been associated with long-term
      changes in cerebral excitability and cognition. Whether recurrent seizures in the
      neonatal rat lead to cell loss in the cerebral cortex is not known. We counted
      cells in the parietal cortex, piriform cortex, and CA3 and CA1 hippocampal
      subfields in young adult rats that had undergone a series of 55 seizures during
      the first 12 days of life. There were no differences in cell counts between the
      controls and rats subjected to neonatal seizures. Like the hippocampus, the
      neonatal pririform and parietal cortex is resistant to seizure-induced cell loss.

PMID- 11978399
TI  - Identification of functional dopamine receptors in human teratocarcinoma NT2
      cells.
AB  - In search of a cellular model suitable for studying molecular events contributing
      to brain disorders, we have characterised the expression and functionality of
      dopamine receptors in human teratocarcinoma NT2 cells. The cells were
      differentiated by a 4-week retinoic acid treatment, followed by a 3-week mitotic
      inhibitor treatment in the absence of retinoic acid. The messages of two D(2)
      like family members, D(2L) and D(3), were expressed in undifferentiated NT2
      cells. The retinoic acid treatment resulted in increased expression of both
      spliced variants of the D(2) receptor, D(2L) and D(2S) isoforms and a significant
      induction of D(1) and D(5) gene transcripts. The same treatment turned off
      expression of the D(3) gene. Further induction of the D(5) gene was observed in
      the post-mitotic NT2N neurons. The NT2N cells stained positively for D(2) and
      D(5) receptor proteins, and the intracellular cyclic AMP level increased in
      response to forskolin, dopamine and the D(1)-receptor agonist SKF-81297.
      Furthermore, dopamine was ineffective in the presence of the D(2) receptor
      agonist PPHT and the D(1) receptor antagonist cis-(z)-flupenthixol. These results
      indicated that upon ligand/agonist/antagonist binding, the receptors could be
      coupled to the adenylyl cyclase system, hence were functional. To our knowledge,
      NT2 is the only human immortalized cell line expressing functional dopamine
      receptors of both families.

PMID- 11978400
TI  - Molecular profiling of behavioural development: differential expression of mRNAs
      for inositol 1,4,5-trisphosphate 3-kinase isoforms in naive and experienced
      honeybees (Apis mellifera).
AB  - In seeking genetic factors that may control the extended behavioural maturation
      of adult honeybees we found that inositol 1,4,5-trisphosphate (IP(3)) 3-kinase, a
      key enzyme in the IP(3)-mediated signalling cascade, is differentially expressed
      in brains of naive, newly emerged bees and experienced foragers. DNA sequencing
      yielded a contig of 21.5 kb spanning the honeybee IP(3)K locus and a 3' flanking
      gene similar to a transcription factor NFR-kappa-B. The IP(3)K locus gives rise
      to three differentially expressed major transcripts produced by alternative
      splicing that encode proteins with identical, highly conserved C-termini and
      distinct, non-conserved N-terminal domains. The type A transcript is dominant in
      the adult brain and its level of expression increases threefold during the first
      4 days of adult development. The type B message is expressed in brains of naive
      bees, but is also found in the thorax and abdomen, whereas transcript C is
      expressed largely in non-neural tissues and in the antenna. In contrast to type A
      message, the brain levels of transcript B decrease during the first 4 days of
      adult life. Our data are evaluated in the context of the contrasting behavioural
      phenotypes of immature and experienced worker honeybees.

PMID- 11978401
TI  - Lidocaine stabilizes the open state of CNS voltage-dependent sodium channels.
AB  - We have previously reported that the lidocaine action is different between CNS
      and muscle batrachotoxin-modified Na+ channels [Salazar et al., J. Gen. Physiol.
      107 (1996) 743-754; Brain Res. 699 (1995) 305-314]. In this study we examined
      lidocaine action on CNS Na+ currents, to investigate the mechanism of lidocaine
      action on this channel isoform and to compare it with that proposed for muscle
      Na+ currents. Na+ currents were measured with the whole cell voltage clamp
      configuration in stably transfected cells expressing the brain alpha-subunit
      (type IIA) by itself (alpha-brain) or together with the brain beta(1)-subunit
      (alphabeta(1)-brain), or the cardiac alpha-subunit (hH1) (alpha-cardiac).
      Lidocaine (100 microM) produced comparable levels of Na+ current block at
      positive potentials and of hyperpolarizing shift of the steady-state inactivation
      curve in alpha-brain and alphabeta(1)-brain Na+ currents. Lidocaine accelerated
      the rates of activation and inactivation, produced an hyperpolarizing shift in
      the steady-state activation curve and increased the current magnitude at negative
      potentials in alpha-brain but not in alphabeta(1)-brain Na+ currents. The
      lidocaine action in alphabeta(1)-brain resembled that observed in alpha-cardiac
      Na+ currents. The lidocaine-induced increase in current magnitude at negative
      potentials and the hyperpolarizing shift in the steady-state activation curve of
      alpha-brain, are novel effects and suggest that lidocaine treatment does not
      always lead to current reduction/block when it interacts with Na+ channels. The
      data are explained by using a modified version of the model proposed by Vedantham
      and Cannon [J. Gen. Physiol., 113 (1999) 7-16] in which we postulate that the
      difference in lidocaine action between alpha-brain and alphabeta(1)-brain Na+
      currents could be explained by differences in the lidocaine action on the open
      channel state.

PMID- 11978402
TI  - Angiotensin protects cortical neurons from hypoxic-induced apoptosis via the
      angiotensin type 2 receptor.
AB  - The effects of angiotensin on mouse cortical neuronal cultures exposed to
      chemical-induced hypoxia was investigated. Cultures exposed to 10 mM sodium azide
      for 5 min showed a 17% increase in apoptosis when assayed 24 h postinsult. The N
      methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocked sodium azide-induced
      cell death suggesting that the NMDA receptor contributes to the mediated cell
      death. Pretreatment of cultured neurons with angiotensin decreased sodium azide
      induced apoptosis by 94%. When the AT(1) receptor was blocked by its receptor
      antagonist, losartan, angiotensin activation of the AT(2) receptor completely
      inhibited sodium azide-induced apoptosis. Pretreatment of neurons with the AT(2)
      receptor antagonist PD123319 resulted in angiotensin reducing sodium azide
      induced apoptosis by 48%. These results demonstrate that angiotensin can
      significantly attenuate sodium azide-induced apoptosis primarily through
      activation of the AT(2) receptor and suggests that angiotensin may have a
      protective role in neurons undergoing ischemic injury.

PMID- 11978403
TI  - Expression of functional N-methyl-D-aspartate receptors during development of
      chick embryo retina cells: in vitro versus in vivo studies.
AB  - The N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors were studied in
      retina cells developing in chick embryos and in retina cells cultured as
      retinospheroids, at the same stages of development. In the retinospheroids, the
      activity of the NMDA receptors was followed by monitoring the changes in the
      intracellular free calcium concentration ([Ca2+](i)), in response to NMDA or to L
      glutamate. The expression of the subunits NMDAR1, NMDAR2A/B and NMDAR2C in the
      retinospheroids and in chick retinas were determined by Western blot analyses.
      The changes in [Ca2+](i) in response to 400 microM NMDA increased from 5 h in
      vitro to 3 days in vitro (DIV) and remained constant until 14 DIV, whereas the
      [Ca2+](i) response to 500 microM L-glutamate increased from 5 h in vitro to 3 DIV
      and decreased slightly until 14 DIV. In the retinospheroids, the expression of
      the NMDAR1 and NMDAR2A/B subunits increased from 5 h in vitro until 14 DIV,
      whereas the NMDAR2C subunit increased from 5 h in vitro until 10 DIV and remained
      constant until 14 DIV. In the retinas, the expression of NMDAR1 increased from
      embryonic day 8 (E8) until E15, decreased until E18, and increased again until
      day 22 (post-hatched 1, PH1). The NMDAR2A/B increased from E8 until E18 and
      decreased slightly until PH1, whereas the NMDAR2C subunit increased from E8 until
      E15, remained constant until E18, and increased again until PH1. The results
      suggest that NMDA receptors are expressed and functionally active at early
      embryonic stages in the retina and in retinospheroids, before synapse formation
      (E12). However, the calcium responses to NMDA were relatively constant from 3 DIV
      until 14 DIV, showing no correlation with the increase in the expression of the
      studied NMDA receptor subunit during the same period. Also, the patterns of NMDA
      receptor subunits expressed in chick embryo retina cells cultured in vitro and in
      retina cells developing in vivo were similar.

PMID- 11978404
TI  - Induction of connexin 37 expression in a rat model of neuropathic pain.
AB  - Activation of cutaneous C-fibers by capsaicin or sciatic nerve transection
      increases the number of astrocytic gap junctions as well as the levels of
      connexin 43 in the dorsal horn on the stimulated side. Changes in connexin 37
      mRNA expression following nerve injury have not been previously documented. We
      examined the role of gap junction protein connexin 37 in neuropathic
      hypersensitivity following peripheral nerve injury. Study results showed
      ipsilaterally increased connexin 37 mRNA levels proximally and distally in rat
      sciatic nerves after injury and behavioral thermal hyperalgesia at 7 and 14 days.
      Proximal and distal connexin 37 mRNA levels returned to baseline by 21 days.
      Sciatic nerve connexin 37 mRNA increases were proportional to the extent of
      thermal hyperalgesia, but skin, muscle, and lumbar spinal cord connexin 37 mRNA
      showed no significant changes. Neuropathic pain relief correlated with
      downregulation of connexin 37 mRNA. Results indicate that upregulation of
      connexin 37 mRNA following sciatic nerve injury correlates with subsequent
      thermal hyperalgesia, which suggests that gap junctions (connexin 37) are
      responsible for the hyperexcitability following peripheral nerve injury.

PMID- 11978405
TI  - Further identification of NSF* as an epilepsy related gene.
AB  - Previous data proved that NSF* was an epilepsy related gene (ERG1). In this
      study, using phosphorothioate oligodeoxynucleotide (PS-ODN), an antisense of NSF
      to downregulate the function of NSF in vitro cultured hippocampus neurons and
      PC12, this treatment simultaneously induced enhancement of the neurite outgrowth
      of hippocampal neurons and PC12, a phenomenon similar to the structural changes
      following epilepsy. Immunocytochemistry analysis showed that the enhancement of
      neurite outgrowth was in a sequence-specific manner and Northern blot confirmed
      that the decrease of NSF mRNA levels in PC12 was in a dose-dependent manner.
      Moreover the expression of NSF was downregulated during differentiation of PC12
      induced by NGF and high KCl. Therefore, providing more evidence to support the
      fact that NSF was an ERG1.

PMID- 11978406
TI  - Protein inhibitor of neuronal nitric oxide synthase interacts with protein kinase
      A inhibitors.
AB  - Protein kinase A (PKA) and neuronal nitric oxide synthase (nNOS) are important
      signaling molecules. It is well known that PKA can specifically phosphorylate
      nNOS. But the underlying molecular mechanism is still obscure. Our data indicate
      that the protein inhibitor of nNOS (PIN) binds to protein kinase A inhibitors
      (PKIs), which suggests that PKIs, together with PIN, might mediate the
      phosphorylation of nNOS by PKA.

PMID- 11978407
TI  - A review of physical phenomena associated with ultrasonic contrast agents and
      illustrative clinical applications.
AB  - Successful clinical applications of contrast agents involve an understanding of
      the physical interaction of ultrasound (US) with contrast agents. This paper
      reviews the physical phenomena involved in these interactions and discusses the
      relevant theoretical background for modeling US-contrast agent interactions.
      Measurement techniques using US to obtain information regarding contrast agents
      are summarized. Illustrative clinical applications are given in the second part
      of the paper. Recent developments in nonlinear imaging techniques and transient
      techniques are reviewed. New methods, such as depletion perfusion measurement,
      and high-frequency applications are included.

PMID- 11978408
TI  - Improved sonographic imaging of hepatic hemangioma with contrast-enhanced coded
      harmonic angiography: comparison with MR imaging.
AB  - The aim of this study was to compare peripheral nodular enhancement with
      centripetal progression on contrast-enhanced coded harmonic angio (CHA) with
      those as seen on magnetic resonance imaging (MRI) scan. A total of 20 patients
      with 24 hemangiomas confirmed by dynamic contrast-enhanced MRI were included in
      this study. All 20 patients were examined with CHA in conjunction with a
      galactose-based microbubble contrast agent (SH U 508A) and with interval delay
      scanning. The pattern and the time of contrast enhancement were recorded on CHA
      images. We compared CHA images with MRI in terms of the similarity of contrast
      enhanced peripheral nodules. The significance of size of tumor and baseline
      echogenicity on the ability to see peripheral nodular enhancement was
      independently assessed. Peripheral nodular enhancement was shown on CHA in 22
      (92%) of 24 hemangiomas. Of 22 hemangiomas, 21 (95%) with peripheral nodular
      enhancement had progressive centripetal fill-in on CHA images. In 4 (80%) of 5
      hemangiomas less than 1.5 cm in diameter, contrast-enhanced peripheral nodules
      were depicted on CHA images. In terms of the similarity of peripheral nodules,
      CHA images showed the similarity more than "similar" grade with MRI in 21 (95%)
      of 22 hemangiomas. This study shows that CHA is approximately equal to MRI in its
      ability to show peripheral nodular enhancement with centripetal progression, even
      in small hemangiomas.

PMID- 11978409
TI  - Clinical significance of abdominal lymphadenopathy in chronic liver disease.
AB  - The possibility of assessing the relationship of ultrasound (US)-detected
      abdominal lymphadenopathy with etiology, biochemical findings, and histologic
      data in patients with chronic liver disease was evaluated. US examination of the
      upper abdomen was performed in 321 consecutive patients with various chronic
      liver disorders and 56 control patients. The prevalence of lymphadenopathy in
      chronic liver disease was 38%. This prevalence varied according to etiology of
      liver disease, from 50% in chronic hepatitis C virus (HCV) to less than 10% in
      alcoholic cirrhosis and hepatitis B-virus (HBV)-related chronic liver disease.
      Patients with lymphadenopathy showed significantly higher serum levels of AST and
      ALT, as well as greater histopathological severity on liver biopsy specimens. In
      anti-HCV positive patients, there were no differences in the prevalence of
      lymphadenopathy according to HCV genotypes, whereas lymphadenopathy occurred less
      frequently in responders to interferon therapy than in nonresponders.

PMID- 11978410
TI  - Contrast-enhanced sonography of the renal transplant using triggered pulse
      inversion imaging: preliminary results.
AB  - The purpose of our study was to quantify renal transplant parenchymal sonographic
      enhancement using pulse-inversion imaging (PII) and intermittent emission after
      contrast administration by means of bolus and infusion techniques, and to
      evaluate renal perfusion functional indices. A total of 34 patients, presenting
      with minor abnormalities (n = 14) and cortical perfusion changes due to
      parenchymal disorders (n = 12) or renal artery stenosis (n = 8) were included.
      Cardiac-triggered contrast-enhanced PII ultrasound (US) was performed after
      administration of SHU 508 A (Schering AG, Berlin, Germany), using a high
      mechanical index, a frame rate of one image every four cardiac cycles for bolus
      study, and a decreasing frame rate for infusion study. Compared to baseline
      values, peak enhancement ratio ranged from 5.6 to 14.7 using a bolus
      administration, and reached a value of 2.1 to 4.0 using infusion technique.
      Qualitative analysis showed heterogeneous enhancement in most allografts
      presenting with acute parenchymal disease (p = 0.03). In bolus studies, time to
      peak, wash-in and wash-out slopes increased in renal transplants with parenchymal
      disease and renal artery stenosis (p = 0.0001). Infusion administration exhibited
      no plateau in signal level, and no significant difference in enhancement ratio
      was found between groups of patients. Triggered PII after contrast agent
      administration provides morphologic and quantitative information about cortical
      vascularity in renal transplants.

PMID- 11978411
TI  - Skin perfusion assessed by contrast ultrasound predicts tissue survival in a free
      flap model.
AB  - The purpose of this study was to assess perfusion in a free skin flap model using
      contrast-enhanced ultrasound (CEU), and to determine if the extent of perfusion
      early after venous occlusion predicted long-term flap survival. Perfusion was
      assessed in an autologous abdominal skin flap and adjacent healthy skin in rats
      using CEU imaging before venous occlusion and following reflow. Perfusion
      assessment was possible in all flaps and quantitative measurements of
      microvascular blood volume (BV) and blood velocity were expressed as a ratio to
      that in the healthy skin. Proximal flap BV 18 h after venous occlusion was
      significantly greater in those that survived (n = 4) vs. those that became
      necrotic (n = 6) (BV ratio 0.8 +/- 0.1 vs. 0.2 +/- 0.1, p = 0.0001). A BV ratio
      of 0.5 predicted graft viability with a sensitivity and specificity of 100%.
      Microvascular blood velocity at 18 h was similar in grafts that survived and
      those that became necrotic. Qualitative assessment of perfusion by a "blinded"
      observer correlated well with quantitative data and predicted flap outcome in all
      cases. We conclude that skin perfusion can be assessed with CEU. Perfusion 18 h
      following a secondary ischemic insult in a free flap accurately predicts
      subsequent tissue survival in this model.

PMID- 11978412
TI  - Ultrasound monitoring of temperature change during radiofrequency ablation:
      preliminary in-vivo results.
AB  - Radiofrequency (RF) ablation is an interstitial focal ablative therapy that can
      be used in a percutaneous fashion and permits in situ destruction of hepatic
      tumors. However, local tumor recurrence rates after RF ablative therapy are as
      high as 34% to 55%, which may be due in part to the inability to monitor
      accurately temperature profiles in the tissue being ablated, and to visualize the
      subsequent zone of necrosis (thermal lesion) formed. The goal of the work
      described in this paper was to investigate methods for the real-time and in vivo
      monitoring of the spatial distribution of heating and temperature elevation to
      achieve better control of the degree of tissue damage during RF ablation therapy.
      Temperature estimates are obtained using a cross-correlation algorithm applied to
      RF ultrasound (US) echo signal data acquired at discrete intervals during
      heating. These temperature maps were used to display the initial temperature rise
      and to continuously update a thermal map of the treated region. Temperature
      monitoring is currently performed using thermosensors on the prongs (tines) of
      the RF ablation probe. However, monitoring the spatial distribution of heating is
      necessary to control the degree of tissue damage produced.

PMID- 11978413
TI  - The temperature dependence of ultrasound-stimulated acoustic emission.
AB  - Given the high variability of tissue properties during sonication, temperature
      monitoring is one of the most crucial components for accurate thermal treatment
      of tissues with focused ultrasound and other thermotherapy devices. Recently, the
      method of ultrasound-stimulated acoustic emission (USAE) has been introduced as a
      potential method for measurements of mechanical properties of tissues. In this
      paper, the dependence of USAE on tissue temperature is determined. Because USAE
      depends on the acoustic and mechanical properties, both of which vary with
      temperature, it is hypothesized that the USAE signal is also temperature
      dependent and in such a way that it can be used to guide thermal therapy. In a
      series of experiments, ex vivo porcine muscle and fat samples were exposed to
      ultrasound at power levels that induce temperature elevation. In both tissue
      types, below the coagulation threshold, the USAE amplitude was found to vary
      linearly with temperature. However, at higher powers, the correlation with
      temperature was lost due mainly to the irreversible nature of the changes in the
      tissue properties. Theoretical simulations were used to interpret the USAE
      response change with temperature involving both reversible and irreversible
      changes and during both heating and cooling. These results indicate that USAE may
      have important promise as a potential method for localizing temperature elevation
      and, thus, thermal surgery monitoring, as well as detection of irreversible
      changes in tissues.

PMID- 11978414
TI  - Physical correlates of the ultrasonic reflectivity of lipid dispersions suitable
      as diagnostic contrast agents.
AB  - The objective of this study was to determine the physical basis of ultrasound
      (US) reflectivity of echogenic lipid dispersions. These dispersions were made
      using a process previously described involving sonication of the lipid in water,
      addition of mannitol, freezing, lyophilization and rehydration. The component
      lipids were egg phosphatidylcholine, dipalmitoylphosphatidylethanolamine,
      dipalmitoylphosphatidylglycerol and cholesterol in a molar ratio of 69:8:8:15.
      Ultrasound reflectivity, as assessed with a 20-MHz intravascular US catheter and
      analyzed using computer-assisted videodensitometry, was found to be sensitive to
      variations in ambient pressure; echogenicity was greatly reduced by exposure to
      0.5 atm vacuum for 10 s or 1.5 atm pressure for 10 s. Pressure changes of the
      magnitude that obtain in the arterial circulation had little effect on
      echogenicity. Vacuum treatment resulted in the release of approximately 100
      microL air from a standard preparation of 10 mg lipid in 1 mL. Maximum ultrasonic
      reflectivity required the presence of 0.1-0.2 mol/L mannitol during the
      lyophilization step; mere addition of mannitol to the lipid lyophilized in the
      absence of mannitol produced nonreflective dispersions. Inclusion of sodium
      phosphate or other electrolytes reduced echogenicity. High echogenicity was
      associated with the presence of large-volume freeze-dried cakes and fusion of
      liposomes (which led to a 10 times increase in liposome diameters) during
      freezing before lyophilization. Lyophilization from water led to liposome fusion,
      but the cakes were small and US reflectivity was weak. Lyophilization from
      solutions of cryoprotectants such as trehalose produced large cakes, but little
      liposome fusion and also led to weak US reflectivity. Filtration through defined
      pores revealed that approximately 50% of the echogenicity originated from
      particles smaller than 1 microm and about 2/3 from particles smaller than 3
      microm. These results indicate that lyophilization from 0.2 mol/L mannitol
      solution generates a disrupted array of lipid bilayers that, upon rehydration,
      fuse and trap small amounts of air distributed among liposome-size particles.

PMID- 11978415
TI  - Time-intensity-based volumetric flow measurements: an in vitro study.
AB  - Ultrasonic contrast agents have been used to assist blood flow measurements.
      Several contrast-specific flow measurement techniques have been proposed during
      the last few years. Among them, a method based on relative enhancement of the
      backscattered signal as a function of time is of particular interest. This method
      is also known as the time-intensity method. The method is based on the indicator
      dilution theory, and the time-intensity curve is used to derive blood flow
      related parameters such as the flow rate and the blood mixing volume. Previous in
      vitro studies done by other research groups were mainly based on a perfusion
      model or an artery model. Results showed that several parameters derived from the
      time-intensity curve had a good correlation with the flow rate under certain
      conditions. However, the studies did not focus on factors such as mixing volume,
      mixing chamber configuration and different types of mixing chamber. In this
      paper, dependence of the time-intensity curve is further studied. Specifically,
      two types of blood-mixing chambers were constructed. One was a spherical
      compartment phantom with two different sizes (260 and 580 mL) and different
      inflow/outflow configurations. The other was a perfusion phantom consisting of
      dialysis cartridges with the volume ranging from 114 to 351 mL. The time
      intensities were also measured at both the input and the output of the mixing
      chamber. A commercial agent (Levovist) and a self-made, albumin-based agent were
      used and the wash-out time constant and the mean transit time were derived for
      flow rates ranging from 500 to 1300 mL/min. For the perfusion phantom, results
      showed that the parameters had a good correlation with both the flow rate and the
      mixing volume. Results from the compartment phantom, on the other hand, indicated
      that the inflow/outflow configuration and the mixing size significantly affected
      the derived time constants. Potential applications of new volumetric flow
      estimation techniques based on both input and output intensities were also
      discussed.

PMID- 11978416
TI  - Estimating the elastographic signal-to-noise ratio using correlation
      coefficients.
AB  - In conventional elastography, strain is estimated from the gradient of the
      displacement (time-delay) estimates. The displacement estimates involve
      estimating the peak location of the cross-correlation function between matching
      pre- and post-compression A-lines. Bias errors in estimating the peak location of
      the cross-correlation function, amplified by the gradient operation on the
      displacement estimates (needed for the computation of the strain), could result
      in values of elastographic signal-to-noise ratio (SNR(e)) that exceed the
      theoretical upper bounds, thereby hindering a consistent interpretation of this
      parameter. These algorithmic errors have not been accounted for by the theory. We
      propose the use of the measured correlation coefficients in the theoretical
      SNR(e) expressions to estimate the SNR(e), rather than computing them directly
      from the elastograms. This methodology results in values of SNR(e) that are lower
      than the theoretical upper bounds, thereby avoiding the problems associated with
      computing SNR(e) directly from the elastograms. Using simulated models of
      uniformly elastic phantoms, a proof of principle of such an SNR(e) measure is
      shown.

PMID- 11978417
TI  - Bone marrow influences quantitative ultrasound measurements in human cancellous
      bone.
AB  - Quantitative ultrasound (QUS) transmission and backscatter measurements were made
      in 46 human cancellous bone specimens from the calcaneus. All QUS measurements
      were made at 35 degrees C, initially with marrow filling the pores and then
      repeated after substituting water for marrow. Bone mineral density (BMD) was
      determined using x-ray absorptiometry. Marrow significantly decreased ultrasound
      (US) velocity, but increased attenuation, attenuation slope and backscatter (p <
      0.001 for all) compared to the water-saturated state. The impact of marrow on QUS
      measurements was greater at lower BMD values (p < 0.05), and was greater in women
      than in men (p < 0.05). QUS measurements in marrow-saturated specimens correlated
      less strongly with BMD than did corresponding measurements in water-saturated
      specimens (p < 0.05), consistent with interspecimen marrow heterogeneity. These
      data indicate that the potential impact of marrow should be considered when
      interpreting clinical QUS measurements. Understanding and exploiting these
      effects could lead to novel approaches for ultrasonic characterisation of both
      bone and marrow.

PMID- 11978418
TI  - Ultrasound enhancement of fibrinolysis at frequencies of 27 to 100 kHz.
AB  - Ultrasound (US) accelerates enzymatic fibrinolysis in vitro and in animal models,
      and may be a useful adjunctive therapy for clinical thrombolysis. Successful
      clinical application will depend on the selection of appropriate US parameters to
      optimize fibrinolytic enhancement while limiting adverse effects, including
      heating. Most studies have been done at megahertz frequencies, but tissue
      penetration is better and heating less at lower frequencies. We have, therefore,
      now investigated the effects of continuous-wave and pulsed US on fibrinolysis at
      midkilohertz frequencies. Fibrinolysis with tissue plasminogen activator (t-PA)
      was measured by solubilization of radiolabeled fibrin exposed to a calibrated US
      field in a temperature-controlled water bath. There was significant enhancement
      of fibrinolysis at frequencies of 27, 40 and 100 kHz, with the greatest effect
      observed at 27 kHz. The largest effect was observed with continuous-wave US, but
      significant acceleration was also observed with peak intensities of 1 W/cm(2)
      duty cycles of 10% and 1%. At a 10% duty cycle, there was approximately 60% of
      the fibrinolytic enhancement observed with continuous-wave exposure, indicating a
      clear advantage of pulsing to optimize fibrinolytic effect and limit exposure. We
      conclude that US in the range of 27 to 100 kHz is effective in accelerating
      fibrinolysis at intensities and pulsing conditions that minimize the probability
      of heating and cavitation in clinical applications.

PMID- 11978419
TI  - Transcranial color-coded sonography in basilar artery stenting.
AB  - Basilar artery (BA) stenting is an emerging technique with promising results in
      revascularization of severe arteriosclerotic stenoses. Because of the limitations
      associated with other noninvasive techniques, we applied transcranial color-coded
      sonography (TCCS) in the follow-up. Successful stent application in two cases of
      acute basilar occlusion caused by thrombosis on pre-existing severe midbasilar
      stenoses was initially confirmed by angiography. Later recanalization was
      controlled noninvasively by magnetic resonance angiography (MRA), computed
      tomographic angiography (CTA) and TCCS. Ultrasound (US) was performed through the
      transtemporal bone window; a contrast-enhancing agent had to be used in one case.
      TCCS showed an orthograde flow in the distal BA in both patients without signs of
      severe stenoses. Transtemporal TCCS was demonstrated to be a noninvasive bedside
      technique in monitoring the patency of the BA after stenting.

PMID- 11978420
TI  - High-intensity focused ultrasound selectively disrupts the blood-brain barrier in
      vivo.
AB  - High-intensity focused ultrasound (HIFU) has been shown to generate lesions that
      destroy brain tissue while disrupting the blood-brain barrier (BBB) in the
      periphery of the lesion. BBB opening, however, has not been shown without damage,
      and the mechanisms by which HIFU induces BBB disruption remain unknown. We show
      that HIFU is capable of reversible, nondestructive, BBB disruption in a targeted
      region-of-interest (ROI) (29 of 55 applications; 26 of 55 applications showed no
      effect); this opening reverses after 72 h. Light microscopy demonstrates that
      HIFU either entirely preserves brain architecture while opening the BBB (18 of 29
      applications), or generates tissue damage in a small volume within the region of
      BBB opening (11 of 29 applications). Electron microscopy supports these
      observations and suggests that HIFU disrupts the BBB by opening capillary
      endothelial cell tight junctions, an isolated ultrastructural effect that is
      different from the mechanisms through which other (untargeted) modalities, such
      as hyperosmotic solutions, hyperthermia and percussive injury disrupt the BBB.

PMID- 11978424
TI  - Preliminary study on antifertility activity of Calotropis procera roots in female
      rats.
AB  - The effect of ethanolic extract of the roots of Calotropis procera has been
      studied in albino rats to explore its antifertility and hormonal activities. A
      strong antiimplantation (inhibition 100%) and uterotropic activity was observed
      at the dose level of 250 mg/kg (1/4 of LD(50)). No antiestrogenic activity could
      be detected.

PMID- 11978425
TI  - Investigations on the antinociceptive activity of crude extracts from Croton
      cajucara leaves in mice.
AB  - The crude leaf extracts of Croton cajucara Benth. were studied for their
      antinociceptive property in chemical and thermal models of nociception in mice.
      All the tested extracts (hexanic, chloroformic and methanolic), at oral doses of
      100 and 200 mg/kg demonstrated significant inhibition of acetic acid-induced
      writhing and the second phase response of formalin, but did not manifest a
      significant effect in hot-plate test.

PMID- 11978426
TI  - OPLC and AMD, recent techniques of planar chromatography: their interest for
      separation and characterization of extractive and synthetic compounds.
AB  - It is always important for the chemist to have good methods of separation,
      characterization and quantitative evaluation for one or several compounds
      resulting from a chemical reaction or an extraction procedure. In this domain the
      chromatographic techniques are choice methods, in particular Over Pressured Layer
      Chromatography (OPLC) and Automated Multiple Development (AMD). They are
      relatively recent methods whose use is unfortunately not yet generalized although
      they give very clean separation. In this paper we present numerous examples of
      the use of these two new types of planar chromatographies and especially the
      results we have obtained in the field of natural products on a wide variety of
      different structures: coumarins, flavonoids, anthocyanins, alkaloids and
      essential oils.

PMID- 11978427
TI  - New neolignans from Talauma ovata.
AB  - The hexane extract of the bark of Talauma ovata yielded three new natural
      neolignans, identified as acetyl oleiferin-C (4), acetyl oleiferin-F (7) and
      acetyl oleiferin-G (8), together with the known compounds dihydroguaiaretic acid
      (1), austrobailignan-5 (2), oleiferin-C (3), austrobailignan-6 (5) and oleiferin
      F (6).

PMID- 11978429
TI  - Chemical constituents of Ganoderma applanatum of British Columbia forests.
AB  - A new compound, ganoderma aldehyde (1),was isolated from the fruiting body of
      Ganoderma applanatum. Its structure was elucidated on the basis of one
      dimensional and two-dimensional NMR as well as MS spectroscopic analysis.

PMID- 11978428
TI  - In vitro tests to evaluate potential biological activity in natural substances.
AB  - The biological activity of polysaccharides from the mycelia of 40 Basidiomycetes
      was studied using an uncommon toxicity test technique, the planaria bioassay, and
      the better known potato disk bioassay. The results showed the utility of this duo
      of 'in vitro' tests as a preliminary screening of the toxicity of substances that
      are present in aqueous fungal extracts.

PMID- 11978430
TI  - Antimicrobial activity of pyrrolizidine alkaloids from Heliotropium subulatum.
AB  - Five pyrrolizidine alkaloids have been isolated from Heliotropium subulatum and
      tested for their antimicrobial activity.

PMID- 11978431
TI  - Hypoglycemic activity of Abutilon indicum leaf extracts in rats.
AB  - Alcohol and water extracts of Abutilon indicum leaves (400 mg/kg, p.o.) showed
      significant hypoglycemic effect in normal rats 4 h after administration (23.10%
      and 26.95%, respectively).

PMID- 11978432
TI  - Antimicrobial and phytochemical studies of Swertia corymbosa.
AB  - The aqueous, methanol, chloroform and hexane extracts of Swertia corymbosa were
      tested (in vitro) for their antimicrobial efficiency. Maximum inhibitory activity
      was noticed against Staphylococcus aureus and Salmonella typhi.

PMID- 11978433
TI  - Antibacterial activity of Terminalia pallida.
AB  - The methanol extract of the dried fruit powder of Terminalia pallida was
      evaluated for antimicrobial activity. The methanol extract showed a broad
      spectrum of antibacterial activity.

PMID- 11978435
TI  - Alkaloids from Senecio aquaticus.
AB  - Erucifoline (1) and 9-angeloylhastanecine (2) were isolated from the aerial parts
      of Senecio aquaticus. Five other pyrrolizidine alkaloids were tentatively
      identified by GC/MS analysis: jacobine; seneciphylline; spartioidine; jacozine;
      and senecionine.

PMID- 11978434
TI  - Antimicrobial activity of Eupatorium ayapana.
AB  - Petroleum ether and methanolic extracts of leaves of Eupatorium ayapana were
      tested for their antimicrobial activity. The petroleum ether extract showed
      higher antibacterial and antifungal activity than the methanolic extract.

PMID- 11978436
TI  - A new flavonol from leaves of Eugenia jambolana.
AB  - Leaves of Eugenia jambolana yielded the new flavonol, myricetin 3-O-(4"-acetyl)
      alpha-L-rhamnopyranoside (1).

PMID- 11978437
TI  - Glucosinolates from Cardaria draba.
AB  - A new glucosinolate salt, L-prolinium 4-(methylsulfinyl)butyl glucosinolate, was
      isolated from the flowering heads of Cardaria draba and characterized by current
      spectroscopic methods.

PMID- 11978443
TI  - Refractive changes after PTK.

PMID- 11978440
TI  - Endophthalmitis.

PMID- 11978442
TI  - Anterior vitrectomy and low-contrast sensitivity in pediatric eyes.

PMID- 11978444
TI  - Microkeratome-assisted posterior keratoplasty.

PMID- 11978446
TI  - Intraocular lens power calculation software.

PMID- 11978445
TI  - Laser in situ keratomileusis flap dehiscence 3 years postoperatively.

PMID- 11978447
TI  - Comments on anesthesia for cataract surgery.

PMID- 11978448
TI  - Consultation section. Refractive surgical problem.

PMID- 11978449
TI  - Minimizing risk to the capsule during surgery for posterior polar cataract.
AB  - Posterior polar cataract is associated with a deficiency of the posterior capsule
      in a high percentage of cases, leading to a high incidence of capsule rupture and
      potential vitreous loss. We describe an approach that minimizes the risk of
      vitreous loss. The key is viscodissection, a technique that can be applicable in
      other situations.

PMID- 11978450
TI  - Viscocanalostomy and phacoviscocanalostomy: long-term results.
AB  - PURPOSE: To determine the safety and efficacy of viscocanalostomy and cataract
      extraction by phacoemulsification combined with viscocanalostomy
      (phacoviscocanalostomy) in the management of medically uncontrolled glaucoma.
      SETTING: Department of Ophthalmic Surgery, Warrington Hospital, Warrington,
      England. METHODS: This prospective nonrandomized study comprised 101 consecutive
      eyes of 73 patients with medically uncontrolled glaucoma having viscocanalostomy
      or phacoviscocanalostomy. Outcomes measured were intraocular pressure (IOP)
      control, visual acuity, gonioscopy, bleb morphology, and complications associated
      with surgery. Examinations were performed preoperatively and 1 and 7 days and 1,
      3, 6, 9, and 12 months postoperatively and then at 6-month intervals. The mean
      follow-up was 23.9 months +/- 11 (SD) (range 6 months to 3.5 years). RESULTS: The
      mean preoperative IOP was 24.9 +/- 5.7 mm Hg on 2.27 +/- 0.8 medications and the
      mean postoperative IOP at last follow-up, 16.14 +/- 2.9 mm Hg on 0.1 medications.
      A postoperative IOP of 21 mm Hg or less was achieved in 93% of eyes. In the
      remaining 7%, an addition of a mean of 1.4 medications achieved an IOP less than
      21 mm Hg. No case required further glaucoma surgery. The mean percentage of IOP
      reduction in eyes having viscocanalostomy alone was 37% and in eyes having
      phacoviscocanalostomy, 33%. Complications were minor and included 4 small
      hyphemas, 5 small choroidal detachments, 1 iris prolapse through the phaco
      incision, and 10 intraoperative microperforations of the trabeculo-Descemet's
      window. Transient postoperative pressure elevations secondary to topical steroids
      occurred in 18% of eyes. CONCLUSIONS: Viscocanalostomy and phacoviscocanalostomy
      were safe and effective in the surgical management of glaucoma and combined
      glaucoma and cataract. There was a low incidence of complications postoperatively
      and throughout the long-term follow-up.

PMID- 11978451
TI  - Midterm ultrasound biomicroscopy findings in eyes with successful
      viscocanalostomy.
AB  - PURPOSE: To show tissue changes using ultrasound biomicroscopy (UBM) in eyes with
      controlled intraocular pressure (IOP) after viscocanalostomy. SETTING:
      Consultores Oftalmologicos, Fundacion Oftalmologica Argentina Jorge Malbran and
      Hospital Santa Lucia, Buenos Aires, Argentina. METHODS: This retrospective
      noncomparative case series comprised 23 eyes of 19 patients with uncontrolled
      open-angle glaucoma who had viscocanalostomy and UBM and a mean follow-up of 20
      months +/- 5.9 (SD) (range 12 to 30 months). The UBM measurements were taken a
      mean of 6.8 +/- 5.9 months (range 3 to 14 months) after the viscocanalostomy. In
      7 eyes, UBM was again performed a mean of 7.8 +/- 4.6 months (range 7 to 9
      months) after the first study. All patients had preoperative and postoperative
      IOP measurements. RESULTS: The mean IOP at last examination was 13.3 +/- 2 mm Hg
      (range 8 to 17 mm Hg). One eye had evidence of a subconjunctival bleb. All eyes
      had a nonreflective scleral chamber and posterior to it, a hyporeflective zone.
      In 7 eyes in which 2 UBMs were performed, the scleral chamber was unchanged 7 to
      9 months after the first study. CONCLUSIONS: The presence of a scleral chamber
      and absence of a subconjunctival filtering bleb are the usual UBM findings in
      eyes with adequate control of IOP several months after viscocanalostomy. These
      findings suggest that viscocanalostomy is successful when a continuous aqueous
      flow through the trabeculo-Descemet's membrane is present, maintaining a scleral
      chamber.

PMID- 11978452
TI  - Laser-assisted deep sclerectomy.
AB  - PURPOSE: To study the clinical effectiveness of deep sclerectomy using the
      erbium:YAG (Er:YAG) laser in patients with open-angle glaucoma (OAG). SETTING:
      Department of Ophthalmology, Institut Universitari Dexeus, Universitat Autonoma
      de Barcelona, Barcelona, Spain. METHODS: This nonrandomized prospective clinical
      study was performed in 46 consecutive eyes with OAG. Seventeen patients had not
      received any treatment for glaucoma. Eight had received 1 medication; 14, 2
      medications; and 7, 3 medications. The mean duration of treatment was 18.3 months
      +/- 9.4 (SD). After mitomycin-C 0.02% was administered for 2 minutes, a
      superficial 4.0 mm x 4.0 mm scleral flap was created and a deep 3.0 mm x 3.0 mm
      scleral ablation was performed with the Er:YAG laser. Schlemm's canal was
      removed, and the cornea was dissected to Descemet's membrane until aqueous humor
      percolated. The scleral flap and conjunctiva were closed. Postoperative follow-up
      examinations were done at 1, 3, and 7 days, 2, 3, and 4 weeks, and then every 3
      months up to 15 months. RESULTS: The mean preoperative intraocular pressure (IOP)
      was 28.3 +/- 6.1 mm Hg. The mean postoperative IOP was 14.1 +/- 3.5 mm Hg at 24
      hours, 16.3 +/- 4.2 mm Hg at 3 months, and 15.3 +/- 2.7 mm Hg at 15 months (P
      <.001). There were no statistically significant differences in IOP by sex or age.
      There was a statistically significant difference between patients receiving no
      medication and those who received more than 2 medications and a treatment period
      longer than 1 year preoperatively (P <.006). The presence of a filtering bleb was
      associated with a longer period of decreased IOP (P <.007). The success rate (IOP
      < or =18 mm Hg without medication) was 93.47% at 1 month and 84.78% at 15 months.
      The number of complications was significantly lower than in previous reports of
      trabeculectomy. One patient lost 2 lines of visual acuity because of cystoid
      macular edema. CONCLUSIONS: Deep sclerectomy using the Er:YAG laser was safe and
      effective in eyes with OAG. More studies are needed to analyze the mechanism of
      lowering IOP.

PMID- 11978453
TI  - Ablation profiles for wavefront-guided correction of myopia and primary spherical
      aberration.
AB  - PURPOSE: To calculate ablation profiles for wavefront-guided correction of
      ametropia and primary spherical aberration. SETTING: Bascom Palmer Eye Institute,
      University of Miami, Miami, Florida, USA. METHODS: The primary spherical
      aberrations of the ocular surfaces of an aspheric eye model were calculated
      before and after simulated ablations for correction of myopia ranging from 0 to
      10 diopters. The corneal asphericity to correct primary spherical aberration and
      the corresponding ablation profiles were also calculated. RESULTS: The corneal
      asphericity factor that produces zero primary spherical aberration ranges from 
      0.45 to -0.47. The calculated ablation profiles are parabolic in first
      approximation, and the ablation depth varies linearly with the amount of
      correction. To control residual primary spherical aberration with a tolerance of
      one-quarter wavelength, the precision of the ablation must range from 0.2 to 0.3
      microm. CONCLUSIONS: Ocular aberrometry and corneal topography can be used to
      calculate ablations for the correction of ametropia and primary spherical
      aberration. Precise control of postoperative spherical aberration appears to be
      feasible in theory.

PMID- 11978454
TI  - Laser in situ keratomileusis for residual myopia after photorefractive
      keratectomy.
AB  - PURPOSE: To evaluate the efficacy and safety of laser in situ keratomileusis
      (LASIK) for myopic regression and undercorrection after photorefractive
      keratectomy (PRK). SETTING: The Eye Institute, Sydney, Australia. METHODS: Fifty
      eyes of 32 patients were treated by LASIK for residual myopia following primary
      PRK. The mean spherical equivalent refraction (SEQ) was -2.92 diopters (D) +/-
      1.57 (SD) (range -0.75 to -7.88 D). The mean refractive cylinder was 0.96 +/-
      0.74 D (range 0 to 3.50 D). For analysis, the eyes were divided into 2 groups:
      those with 0 or low corneal haze (Group 1) and those with severe corneal haze
      (Group 2). In Group 1, the SEQ was -1.99 +/- 0.79 D (range -0.75 to -3.75 D) and
      in Group 2, -3.77 +/- 1.62 D (range -0.75 to -7.90 D). The procedure was
      performed using the Chiron Automated Corneal Shaper and the Summit Apex Plus
      laser. The mean interval between PRK and LASIK was 25 months (range 9 to 59
      months). The following parameters were studied before and after LASIK
      retreatment: SEQ, mean refractive cylinder, uncorrected visual acuity (UCVA), and
      best corrected visual acuity (BCVA). Complications after LASIK retreatment were
      evaluated. RESULTS: Six months after LASIK, the mean SEQ in all eyes was -0.65 +/
      0.86 D (range +1.50 to -3.35 D); 70.0% of eyes were within +/-1.00 D of
      emmetropia and the UCVA was 6/12 or better in 72.5%. The mean SEQ in Group 1 was 
      0.22 +/- 0.55 D (range -0.88 to -1.50 D) and in Group 2, -0.97+/- 0.92 D (range
      0.12 to -3.25 D); the UCVA was 6/12 or better in 94.0% of eyes in Group 1 and in
      56.0% in Group 2. No statistically significant between-group difference was found
      in lines of Snellen acuity lost or gained at 6 months. No eye lost more than 1
      line of BCVA. CONCLUSIONS: Laser in situ keratomileusis appears to be a safe,
      effective, and predictable procedure for treating eyes with 0 or low haze with
      residual myopia after PRK. It is less predictable in eyes with severe haze.

PMID- 11978455
TI  - Subclinical inflammation after laser in situ keratomileusis in corneal grafts.
AB  - PURPOSE: To evaluate postoperative inflammatory reaction in the eye after laser
      in situ keratomileusis (LASIK) in corneal grafts. SETTING: Department of
      Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS:
      Ten eyes of 9 patients with penetrating keratoplasty (PKP) and significant
      postoperative refractive errors and astigmatism had LASIK 22 months or more after
      the PKP. All patients were treated with the VISX Star excimer laser and the
      Bausch & Lomb Hansatome microkeratome. Preoperative and early postoperative
      inflammation was evaluated by quantifying the aqueous flare intensity with a
      laser flare photometer (Kowa FM-500). A full ophthalmic assessment was also
      performed before LASIK and up to 6 months postoperatively. RESULTS: The
      inflammatory response was mild and limited to the first postoperative hour. The
      mean anterior chamber flare increased from 6.0 photons/millisecond (ph/ms)
      preoperatively to 14.0 ph/ms at 1 hour and then decreased to 6.7 ph/ms (hour 3),
      6.8 ph/ms (day 1), and 8.2 ph/ms (day 7). The mean spherical equivalent (SE)
      refraction decreased from -3.81 diopters (D) (range -9.63 to -0.25 D) to -0.46 D
      (range -1.13 to +0.38 D), and the mean preoperative astigmatism decreased from
      3.0 D (range 6.5 to 0.5 D) to 0.7 D (range 0.0 to 2.0 D). At the last
      examination, 9 eyes were within +/-1.0 D (6 within +/-0.5 D) and all were within
      +/-1.5 D of the intended SE refraction. Three eyes achieved full cylinder
      correction, and 7 were within +/-1.0 D of the intended correction. Eight eyes had
      a best corrected visual acuity of 20/40 or better (unchanged or gain of 1 to 4
      lines [6], loss of 1 line [1], and loss of 3 lines [1]), and 8 had an uncorrected
      visual acuity of 20/50 or better. CONCLUSIONS: Uneventful LASIK induced subtle,
      short-lasting anterior chamber flare when measured by the laser flare meter. In
      corneal grafts, LASIK appeared to be a safe and effective procedure for residual
      refractive errors.

PMID- 11978456
TI  - Defining the content of patient questionnaires: reasons for seeking laser in situ
      keratomileusis for myopia.
AB  - PURPOSE: To determine the relative importance of patients' motives for having
      laser in situ keratomileusis (LASIK) for myopia. SETTING: The Corneal Diseases
      and Excimer Laser Research Unit, University of Dundee, Ninewells Hospital and
      Medical School, Dundee, Scotland. METHODS: Twenty-one cards printed with
      potential reasons for having LASIK and 3 blank cards for respondents to include
      additional motives were posted to 71 patients who had myopic LASIK. The cards
      were ranked by each respondent in order of personal importance and returned for
      analysis. RESULTS: The response rate was 77.5%. The mean age of the 19 male and
      37 female respondents was 41.7 years +/- 9.3 (SD) and the mean preoperative
      spherical equivalent, -9.26 +/- 4.58 diopters. The primary reasons for seeking
      treatment (percentage of respondents ranking topic within the top 5) were
      improvement of unaided social vision (69.1%), intolerance to spectacles/contact
      lenses (65.5%), and freedom from spectacles/contact lenses (61.8%). Almost 70% of
      respondents ranked 1 of these reasons as the most important. General
      inconvenience of spectacles/contact lenses and the desire to pursue sports and
      leisure activities also ranked high (52.7% and 36.4%, respectively). CONCLUSIONS:
      Consistent with previous work, better unaided vision, combined with the
      inconvenience of or intolerance to spectacles or contact lenses, provided the
      main incentives to have LASIK for myopia, while improved cosmesis was relatively
      unimportant (29.1%). The results of this study will allow the design of
      satisfaction questionnaires that are better directed toward establishing
      satisfaction of specific, relevant functional and psychological aspects of
      refractive surgery that are important to patients.

PMID- 11978457
TI  - Reasons for not performing refractive surgery.
AB  - PURPOSE: To analyze the reasons that laser in situ keratomileusis (LASIK) or
      photorefractive keratectomy (PRK) were not performed in patients who requested
      surgical correction of their refractive errors. SETTING: Minamiaoyama Eye Clinic,
      Tokyo, Japan. METHODS: This retrospective review comprised 2784 consecutive
      patients who visited our clinic between June 1997 and August 2000. The reasons
      they did not receive refractive surgery (PRK or LASIK) were analyzed. RESULTS:
      Among the 2784 patients who requested surgery for refractive errors, 2079
      patients (74.7%) had PRK or LASIK and 705 patients (25.3%) did not. The most
      common reasons for not treating patients surgically were myopia greater than 
      12.0 diopters and/or high astigmatism (20.7%), insufficient corneal thickness
      (8.2%), keratoconus (6.4%), cataract (5.7%), and hyperopia and/or hyperopic
      astigmatism (4.1%). CONCLUSIONS: Patients who request surgery have a variety of
      problems. Attention must be given to these individual problems, and the
      indications must be considered.

PMID- 11978458
TI  - Corneal flap thickness in laser in situ keratomileusis using the summit Krumeich
      Barraquer microkeratome.
AB  - PURPOSE: To evaluate the thickness of corneal flaps created by the Summit
      Krumeich-Barraquer microkeratome (SKBM) (Alcon Surgical) and identify factors
      that may influence flap thickness. SETTING: SSK Ankara Eye Hospital, Ankara,
      Turkey. METHODS: Seventy-eight eyes of 50 patients who had laser in situ
      keratomileusis with the Asclepion-Meditec MEL 70 G-Scan excimer laser and the
      SKBM were prospectively evaluated. Preoperatively, the central corneal thickness,
      keratometry, visual acuity, and manifest refraction were measured. The
      microkeratome with the suction ring designed to create 160 microm thick and 9.0
      to 9.5 mm diameter flaps was used in all eyes. Stromal bed thickness was measured
      with the Pachette ultrasonic pachymeter (DGH Technology, Inc.) after the flap was
      lifted. Flap thickness was calculated by subtracting the central stromal bed
      thickness from the preoperative central corneal thickness. RESULTS: The mean
      preoperative central corneal thickness was 546.7 microm +/- 31.9 (SD), the mean
      manifest refraction spherical equivalent was -6.8 +/- 3.4 diopters (D), and the
      mean corneal refractive power was 42.9 +/- 1.5 D. The mean corneal flap thickness
      created by the microkeratome was 154.9 +/- 19.3 microm (range 101 to 202 microm).
      There was no correlation between corneal flap thickness and the degree of myopia
      (P =.151) or the corneal refractive power (P =.257). There was a linear
      relationship between flap thickness and the preoperative central corneal
      thickness (P =.000). A posterior corneal stroma thicker than 250 microm was
      preserved in 87 eyes (98.9%). CONCLUSIONS: The SKBM produced corneal flaps that
      were consistently close to the intended thickness. Corneal flap thickness did not
      appear to be influenced by the degree of myopia or the corneal refractive power;
      however, there was a linear relationship between flap thickness and the
      preoperative central corneal thickness.

PMID- 11978459
TI  - Implantation of spheric phakic posterior chamber intraocular lenses in astigmatic
      eyes.
AB  - PURPOSE: To evaluate the simultaneous correction of spherical and cylindrical
      ametropia through implantation of phakic posterior chamber (PC) intraocular
      lenses (IOLs) combined with a limbal incision. SETTING: Eye Department,
      Schlosspark-Klinik, Charite University Berlin, Berlin, Germany. METHODS: In 5
      hyperopic and 7 myopic eyes with varying astigmatic measurements, a refractive
      correction was achieved by implanting phakic PC IOLs (Staar Surgical Co.) and
      performing limbal incisions of different lengths. The incisions were placed
      approximately 1.0 mm from the limbus with a mean depth of 600 microm and a length
      of 6.0 mm +/- 0.9 (SD). The phakic PC IOLs were implanted after the limbal
      incisions were placed. RESULTS: In the 5 hyperopic eyes, the astigmatism
      decreased from 2.7 diopters (D) preoperatively to 0.5 D at a mean of 7.5 +/- 1.7
      months without alteration of the axis of highest bowing. In the 7 myopic eyes, it
      decreased from 2.2 D preoperatively to 0.7 D at 7.2 +/- 2.6 months. In 3
      hyperopic eyes and 1 myopic eye, the limbal incisions were repeated. CONCLUSIONS:
      The observed mean postoperative spherical equivalent was close to emmetropia.
      Repeat incisions were necessary in eyes exhibiting astigmatism greater than 2.5
      D. The advantage of limbal incisions in combination with phakic PC IOL
      implantation is demonstrated not only by the astigmatic reduction but also by the
      axis stability. It will be interesting to see whether toric phakic lenses can
      achieve the same postoperative results, especially in axis stability and
      reduction of higher degrees of astigmatism.

PMID- 11978460
TI  - Refractive change in pediatric pseudophakia: 6-year follow-up.
AB  - PURPOSE: To evaluate the long-term evolution of refractive error changes in eyes
      of children who have primary intraocular lens (IOL) implantation to allow more
      accurate prediction of what IOL power should be implanted at a given age.
      SETTING: Department of Ophthalmology, Indiana University School of Medicine,
      Indianapolis, Indiana, USA. METHODS: This study comprised all children between 2
      and 15 years of age who had posterior chamber IOL implantation and who were
      followed for a minimum of 4 years postoperatively. Thirty-eight eyes of 27
      patients with a mean follow-up of 6.1 years were evaluated. All refractions were
      performed manually by an experienced pediatric ophthalmologist. RESULTS: Children
      operated on at age 2 or 3 years had a mean myopic shift of 4.60 diopters (D)
      (range 0.50 to 10.75 D) over a mean of 5.8 years postoperatively. Children
      operated on at age 6 or 7 years had a mean myopic shift of 2.68 D (range 0.50 to
      6.60 D) over a mean of 5.3 years. Children operated on at age 8 or 9 years had a
      mean myopic shift of 1.25 D (range -0.75 to 2.60 D) over a mean of 6.8 years.
      Patients operated on between ages 10 and 15 years had a mean shift of 0.61 D
      (range 0 to 1.90 D) over a mean of 5.7 years. CONCLUSIONS: The mean rate of
      myopic shift decreased throughout childhood, and the range of shift among
      individuals narrowed as patient age increased. However, the ability to predict
      future myopic shift for a given individual remains difficult, especially in
      younger patients.

PMID- 11978461
TI  - Surgical management of the lens and retrolenticular fibrotic membranes associated
      with persistent fetal vasculature.
AB  - PURPOSE: To evaluate a surgical technique that allows safe, effective, near-total
      removal of retrolenticular fibrotic membranes in eyes with persistent fetal
      vasculature syndrome (PFVS). SETTING: Pediatric ophthalmologist's academic
      practice. METHODS: This retrospective review comprised 5 children (6 eyes) who
      had excision of a retrolenticular fibrovascular membrane during cataract surgery
      over a 6-month period. Long, spoke-like radial incisions of the membrane were
      made to the ciliary processes, resulting in wedge-shaped segmentation of the
      membrane. A vitrector was used to excise each wedge and perform an anterior
      vitrectomy. RESULTS: The mean age at time of surgery was 8 months (range 1 to 24
      months) and the mean follow-up, 9 months (range 2 to 13 months). The membrane was
      successfully removed in all eyes. One eye of a patient who did not comply with
      the postoperative medical regimen or follow-up developed pupillary block glaucoma
      requiring pupilloplasty and trabeculectomy. CONCLUSION: This anterior surgical
      technique to remove tenacious retrolenticular membranes associated with PFVS was
      effective, allowing near-total removal of the offending fibrovascular membrane.

PMID- 11978462
TI  - Effect of temporal and nasal unsutured limbal tunnel incisions on induced
      astigmatism after phacoemulsification.
AB  - PURPOSE: To compare the surgically induced corneal astigmatism after unsutured
      temporal and nasal unsutured limbal tunnel incisions. SETTING: Departments of
      Ophthalmology, Marienhospital, Aachen, and Johann Wolfgang Goethe-University,
      Frankfurt am Main, Germany. METHODS: In a prospective clinical study, 42 eyes of
      21 patients with a mean age of 75.1 years had phacoemulsification and
      implantation of a foldable hydrophobic acrylic intraocular lens using a 3.6 to
      3.8 mm unsutured limbal tunnel incision. The right eye always received a temporal
      incision and the left eye, a nasal incision. Computerized videokeratography was
      performed preoperatively and 2 weeks and 6 months postoperatively. Surgically
      induced astigmatism was calculated by vector analysis using the Holladay-Cravy
      Koch formula. The 2 groups were compared using a paired Wilcoxon test. RESULTS:
      The mean surgically induced corneal astigmatism in the temporal incision group
      was 0.62 diopters (D) +/- 0.48 (SD) 2 weeks postoperatively and 0.47 +/- 0.32 D
      at 6 months and in the nasal incision group, 1.55 +/- 0.84 D and 1.05 +/- 0.57 D,
      respectively. The difference between the groups was statistically significant (P
      <.05). CONCLUSIONS: There was a highly statistically significant difference in
      surgically induced corneal astigmatism after temporal and nasal unsutured limbal
      tunnel incisions. The degree of induced astigmatism and the difference between
      the temporal and the nasal incisions decreased over time. A nasal tunnel incision
      is not appropriate for astigmatism-neutral surgery.

PMID- 11978463
TI  - Bacterial contamination of the anterior chamber during phacoemulsification
      cataract surgery.
AB  - PURPOSE: To determine the incidence of bacterial contamination of the anterior
      chamber after phacoemulsification cataract surgery with intraocular lens (IOL)
      implantation. SETTING: Department of Ophthalmology, Royal Prince Alfred Hospital,
      Sydney, Australia. METHODS: Ninety-eight consecutive eyes of 96 patients having
      phacoemulsification cataract surgery with IOL implantation were included in this
      prospective study. Two intraoperative anterior chamber aspirates were obtained
      from each patient, 1 taken at the start and the other at the conclusion of
      surgery. In addition, preoperative and postoperative conjunctival swabs were
      acquired. The 4 specimens were cultured using direct culturing techniques under
      aerobic and anaerobic conditions for 14 days. No preoperative antibiotics were
      used. RESULTS: The incidence of intraoperative anterior chamber contamination was
      0% (95% confidence interval, 0%-3.7%) as all intraoperative anterior chamber
      samples proved culture negative. Sixty-five percent of the preoperative
      conjunctival swabs were positive for growth, with corynebacteria, coagulase
      negative staphylococci, and Propionibacterium acnes being the most frequently
      cultured organisms. Sixteen percent of the postoperative conjunctival swabs were
      positive for growth, with corynebacteria and coagulase-negative staphylococci
      being the most common bacteria. One patient developed culture-positive
      postoperative endophthalmitis; using pulsed-field gel electrophoresis for further
      typing, the implicated Staphylococcus epidermidis was indistinguishable from that
      isolated from the patient's preoperative conjunctival swab. CONCLUSIONS: The
      bacterial contamination rate of the anterior chamber after phacoemulsification
      and IOL implantation was extremely low. Additional findings support the
      conjunctiva as being a primary source of bacteria causing postoperative
      endophthalmitis as well as the ability of povidone-iodine to reduce the
      conjunctival bacterial load.

PMID- 11978464
TI  - Combined lidocaine 1% and hydroxypropyl methylcellulose 2.25% as a single
      anesthetic/ viscoelastic agent in phacoemulsification.
AB  - PURPOSE: To evaluate the use of a mixture of hydroxypropyl methylcellulose 2.25%
      (HPMC) and lidocaine 1% (final concentrations) as a single
      viscoelastic/anesthetic agent to achieve proper anesthesia and viscoelastic
      properties during phacoemulsification. SETTINGS: Department of Ophthalmology,
      Cairo University, Cairo, Egypt. METHODS: This prospective randomized study
      comprised 70 eyes having routine phacoemulsification. Patients had the HPMC
      lidocaine mixture (n = 35) or pure HPMC 2.25% (n = 35) injected before
      capsulorhexis and again before intraocular lens implantation. The results were
      evaluated by a pain/discomfort score postoperatively. RESULTS: The difference in
      medians of the overall intraoperative pain/discomfort scores between the 2 groups
      was not statistically significant. However, mild pain/discomfort was reported by
      60.0% in the pure HPMC group and by 31.4% in the HPMC-lidocaine mixture group.
      Moderate pain/discomfort was reported by 28.6% and 5.7%, respectively. The
      difference between the 2 groups was statistically significant (P =.001).
      CONCLUSION: The use of a mixture of HPMC 2.25% and lidocaine 1% rather than a
      regular viscoelastic agent resulted in clinically and statistically significantly
      reduced pain/discomfort during phacoemulsification.

PMID- 11978465
TI  - Phacoemulsification and intraocular lens implantation in nanophthalmic eyes:
      report of a medium-size series.
AB  - PURPOSE: To evaluate the outcomes in nanophthalmic eyes that had
      phacoemulsification and intraocular lens (IOL) implantation. SETTING: Toronto
      Western Hospital, University of Toronto, Toronto, Ontario, Canada. METHODS: Six
      nanophthalmic eyes of 4 patients had uneventful phacoemulsification and posterior
      chamber IOL implantation with a retrobulbar or peribulbar block. All operations
      were performed by 1 surgeon. Patients ranged in age from 41 to 70 years. RESULTS:
      The visual acuity remained stable or improved in all 6 eyes. Glaucoma control was
      maintained or improved in 5 eyes. CONCLUSION: The results indicate that small
      incision cataract surgery, although challenging, is safe and diminishes the need
      for prophylactic sclerotomies in these high-risk eyes.

PMID- 11978466
TI  - Effect of a capsular tension ring on intraocular lens decentration and tilting
      after cataract surgery.
AB  - PURPOSE: To evaluate the effect of a capsular tension ring (CTR) on the tilting
      and decentration of intraocular lenses (IOLs) after cataract surgery. SETTING:
      Department of Ophthalmology, Ilsan Paik Hospital, Inje University, Kyunggyi-do,
      Korea. METHODS: Cataract surgery was performed in both eyes of 20 patients
      ranging in age from 57 to 75 years. The 40 eyes were divided into 2 groups based
      on whether a CTR (Lucid Korea) was implanted. Each patient received a CTR in 1
      eye only. All IOLs (AcrySof MA60BM, Alcon) were implanted in the capsular bag
      after a continuous curvilinear capsulorhexis smaller than the IOL optic was
      created and phacoemulsification performed. The extent of IOL tilting and
      decentration was measured with the EAS-1000 anterior eye segment analysis system
      7, 30, and 60 days after surgery. RESULTS: The extent of IOL decentration was
      statistically significantly less in eyes with both an IOL and CTR than in those
      with an IOL only. The mean decentration in the CTR-IOL group was 0.38 mm +/- 0.16
      (SD) at 7 days, 0.43 +/- 0.15 mm at 30 days, and 0.42 +/- 0.17 mm at 60 days. The
      mean values in the IOL-only group were 0.49 +/- 0.11 mm, 0.53 +/- 0.14 mm, and
      0.57 +/- 0.16 mm, respectively. The amount of IOL tilting was also significantly
      less in the CTR-IOL group. The mean tilting in the CTR-IOL group was 2.22 +/-
      0.46 degrees at 7 days, 2.36 +/- 0.50 degrees at 30 days, and 2.47 +/- 0.40
      degrees at 60 days. The mean values in the IOL-only group were 3.14 +/- 0.65
      degrees, 2.91 +/- 0.67 degrees, and 3.06 +/- 0.56 degrees, respectively.
      CONCLUSION: These results indicate that the CTR reduces undesirable postsurgical
      IOL movement for at least 60 days.

PMID- 11978467
TI  - Visual outcomes after vitreous loss during cataract surgery performed by
      residents.
AB  - PURPOSE: To evaluate the visual outcomes after vitreous loss during cataract
      surgery performed by residents. SETTING: Parkland Memorial Hospital, Dallas,
      Texas, USA. METHODS: A retrospective chart review of all patients who had
      cataract extraction complicated by vitreous loss from 1997 through 1999 was
      conducted. All surgery was performed by third-year ophthalmology residents.
      RESULTS: In 1400 cataract surgeries, 63 cases of vitreous loss (rate 4.5%) were
      identified. One case had less than 1 month of follow-up and was excluded from
      further analysis. Of the 62 remaining cases, 53 had phacoemulsification, 7
      extracapsular cataract extraction (ECCE), 1 phacoemulsification converted to
      ECCE, and 1 intracapsular cataract extraction. Thirty-two eyes had a sulcus
      fixated posterior chamber intraocular lens (PC IOL) implanted, 20 an anterior
      chamber IOL, and 7 a PC IOL in the capsular bag; 3 eyes were left aphakic at the
      time of initial surgery. Overall, 77% of patients had a postoperative best
      corrected visual acuity (BCVA) of 20/40 or better. Of the 14 patients who did not
      have a BCVA of 20/40 or better, 9 had preexisting ocular pathology affecting
      vision. If these 9 patients are excluded, 91% of patients with vitreous loss had
      a BCVA of 20/40 or better. Six patients (10%) developed clinical cystoid macular
      edema. No patient with vitreous loss developed a retinal detachment or
      endophthalmitis. CONCLUSIONS: Good visual acuity can be achieved after resident
      cataract surgery complicated by vitreous loss. The rate of vitreous loss in this
      study is consistent with that in previous reports of resident cataract surgery in
      the literature.

PMID- 11978468
TI  - Prediction of axial length on the basis of vitreous body length and lens
      thickness: retrospective echobiometric study.
AB  - PURPOSE: To examine the predictability of axial length measurement when lens
      thickness and vitreous body length are known. SETTING: Center of Ophthalmology,
      University of Cologne, Cologne, Germany. METHODS: This study comprised 227
      patients with a mean age of 70.01 years +/- 12.47 (SD). None of the eyes examined
      had a history of surgery or trauma. Patients with systemic disease were excluded
      from the study. Before cataract surgery, the length of the vitreous body and
      thickness of the lens were measured and the correlation between these data and
      the axial length was evaluated. Two ultrasonic devices were used for biometric
      measurements: the BMS 811 Biometric System (Grieshaber) and the Cooper Vision
      Ultrascan Digital A+B-Scan 2000. The correlations between the axial length and
      vitreous body length and the lens thickness and vitreous body length were
      analyzed using multiple linear regression. RESULTS: The BMS 811 provided the best
      prediction of axial length based on vitreous body length. Considering sex but not
      age significantly improved the model fit. With the BMS 811, the following formula
      was developed to predict axial length: Axial length (mm) = 7.129 mm + 0.095 mm x
      sex (female = 0, male = 1) + 1.040 x vitreous body length (mm). An approximate
      95% prediction limit may be calculated by the following formula: Axial length
      (mm) +/- 2 x 0.413 mm. CONCLUSIONS: This study yielded an easy-to-use formula for
      predicting the axial length using the vitreous body length and the patient's sex.
      The remaining error in prediction is likely to be the result of patient
      heterogeneity in age, ocular globe size, and lens thickness (cataract formation).
      Good prediction of the axial length is important to refractive outcomes to
      distinguish corneal myopia from axial length myopia to choose grafts and the
      opening size in penetrating keratoplasty. Further studies to detect a clinically
      relevant improvement in such outcomes are required to assess the utility of the
      prediction formula.

PMID- 11978469
TI  - Corneal lenticule harvest using a microkeratome and an artificial anterior
      chamber system at high intrachamber pressure.
AB  - PURPOSE: To evaluate the safety and accuracy of a manual microkeratome and an
      artificial anterior chamber used at high intrachamber pressure to harvest corneal
      lenticules for lamellar keratoplasty. SETTING: Department of Ophthalmology,
      University of California, Irvine, California, USA. METHODS: Forty-seven human eye
      bank corneoscleral rims were mounted on an artificial anterior chamber. A manual
      microkeratome was used to perform lamellar keratectomy at a mean intrachamber
      pressure of 95.8 mm hg +/- 4.8 (sd). Two thicknesses (300 microm and 360 microm
      microkeratome heads) and diameters (8.0 mm and 9.0 mm) were attempted, and the
      resultant lenticules were analyzed by pachymetry and digital photography.
      RESULTS: In the 9.0 mm/360 microm group, corneal perforation occurred in 12 of 17
      lenticules (71.2%). Except for this group, 24 of 30 corneas (80.0%) showed a less
      than 0.5 mm deviation from the expected diameter. Neither the horizontal nor the
      vertical diameter differences were statistically significant (P >.05). The
      difference between the horizontal and vertical diameters was within +/-0.2 mm in
      23 corneas (76.7%). Three (10.0%) corneal beds contained a slightly uneven
      keratectomy margin. CONCLUSIONS: This system provided accurate and smooth
      lenticules for lamellar keratoplasty. The precision and accuracy of the obtained
      corneal lenticules were better than those in previous reports. However, the 9.0
      mm diameter/360 microm thickness head with high intrachamber pressure should not
      be applied in the clinical setting without further testing. In this laboratory
      study, a minimal corneal thickness of 588 microm was required to avoid
      perforation.

PMID- 11978470
TI  - Use of bipolar diathermy to prevent posterior capsule opacification(1).
AB  - PURPOSE: To determine the feasibility of using directed bipolar diathermy to
      eliminate or reduce the formation of new cortical lens material following
      phacoemulsification in a rabbit model. SETTING: Department of Research &
      Development, Bausch & Lomb Surgical, and Department of Ophthalmology, St. Louis
      University, St. Louis, Missouri, USA. METHODS: A rabbit model for posterior
      capsule opacification (PCO) was used. A continuous curvilinear capsulorhexis was
      performed followed by phacoemulsification to remove cortical lens material. In 2
      experimental groups, modified bipolar instruments were used to apply diathermy to
      residual lens epithelial cells using an intracapsular or extracapsular method of
      application. Postoperative clinical examinations were at 1, 3, and 7 days and
      then weekly up to 60 days. Selected animals were followed for a longer period.
      Capsule integrity was evaluated by measuring the pressure required to rupture the
      capsule in similarly treated porcine eyes. RESULTS: Diathermy prevented PCO in 4
      of 4 eyes in the intracapsular treatment group and 4 of 5 in the extracapsular
      group. Eyes remained free of new lens cortex for the life of the animal, which
      was as long as 18 months. New cortical material was detected after 35 days in 1
      animal in the extracapsular group. Mean time for the formation of observable
      cortical material was 29 days +/- 5 (SD) in the control animals. Physical
      measurements did not detect a reduction in capsule integrity with diathermy
      treatment. The extracapsular treatment method resulted in fewer iris
      complications. CONCLUSIONS: Directed diathermy has the potential to eliminate
      secondary cataract formation with minimal damage to collateral tissues.

PMID- 11978471
TI  - Bipseudophakia: clinicopathological correlation of a dropped lens.
AB  - PURPOSE: To examine postmortem human globes containing an anterior chamber and a
      posterior chamber intraocular lens (IOL). SETTING: Center for Research on Ocular
      Therapeutics and Biodevices, Storm Eye Institute, Charleston, South Carolina,
      USA. METHODS: The globes were sectioned at the equator, and the anterior and
      posterior segments were macroscopically examined. Gross photographs were taken
      using the Miyake-Apple posterior photographic technique. Histological sections
      were cut and stained with hematoxylin and eosin, periodic acid-Schiff, and
      Masson's trichrome. RESULTS: Histopathological findings included a large
      Soemmering's ring, a tear in the posterior capsule, 1 haptic of the anterior
      chamber IOL displaced into the iridectomy, thin and atrophic corneal epithelium,
      separation of Bowman's layer and stroma by fibrovascular tissue, and atrophy of
      the retinal ganglion cell layer and nerve fiber layer. CONCLUSION: In cases in
      which secondary IOL implantation is indicated, removing the dislocated IOL
      appears to be a reasonable choice.

PMID- 11978472
TI  - Management of myopic astigmatism with phakic intraocular lens implantation.
AB  - A 48-year-old woman presented with a manifest refraction of -9.25 -2.25 x 98 that
      resulted in a best corrected visual acuity (BCVA) of 20/20(-2) in the right eye.
      She was contact lens intolerant but was not a good candidate for laser in situ
      keratomileusis because of a thin cornea. A phakic posterior chamber intraocular
      lens (IOL) with a toric optic was implanted with no operative complications. One
      day after surgery, the uncorrected visual acuity (UCVA) was 20/15. Five months
      postoperatively, the UCVA in the operated eye was 20/15 with a manifest
      refraction of +0.25 -0.25 x 60 and a BCVA of 20/15. No changes to the crystalline
      lens or anterior lens capsule were seen. This is the first report of implantation
      of a toric phakic IOL in North America.

PMID- 11978473
TI  - Bilateral Mycobacterium abscessus keratitis after laser in situ keratomileusis.
AB  - A 35-year-old man was diagnosed with Mycobacterium abscessus keratitis in the
      left eye 3 weeks after bilateral laser in situ keratomileusis (LASIK). Infection
      in the right eye developed 6 weeks after surgery. Despite aggressive treatment
      with topical amikacin and clarithromycin and oral clarithromycin, the infection
      progressed in both eyes. To improve antibiotic penetration, the LASIK flap was
      removed in both eyes. Culture positivity was prolonged; however, after 8 weeks of
      intensive topical antibiotics, the infection was eradicated. The final best
      corrected visual acuity was 20/30 in both eyes.

PMID- 11978474
TI  - Bilateral peripheral corneal infiltrates after simultaneous myopic laser in situ
      keratomileusis.
AB  - We describe a patient with multiple superior corneal infiltrates in both eyes,
      separated from the limbus by an intervening clear zone, that appeared 1 day after
      uneventful laser in situ keratomileusis. The overlying epithelium was intact, and
      the flap and interface were uninvolved. Based on these features, a clinical
      diagnosis of sterile corneal infiltrates was made and the eyes were treated with
      topical antibiotics and steroids. The infiltrates resolved during the ensuing
      weeks without corneal scarring. Good visual acuity was maintained. Recognition of
      this benign complication is important because aggressive corneal scrapings are
      not required. The infiltrates appear to be immunogenic in origin, although the
      exact etiopathogenesis is not clear.

PMID- 11978475
TI  - Corneal ulcer of the side port after phacoemulsification induced by Acinetobacter
      baumannii.
AB  - A 75-year-old man had clear corneal phacoemulsification using a temporal approach
      in the left eye. Two months after surgery, a focal corneal epithelial defect
      developed with infiltration near the lower limbus on the site of the side-port
      incision. The culture of corneal scrapping grew Acinetobacter baumannii, which is
      resistant to most ordinary antibiotics in sensitivity tests. After appropriate
      antibiotic treatment, the ulcer healed gradually with vessel ingrowth.
      Acinetobacter baumannii is usually found in nosocomial infection of immune
      compromised patients in the intensive care unit. It is a rare pathogen of
      infectious keratitis. Our case, with its unusual infection site, may point to
      potential risk factors for this pathogen.

PMID- 11978476
TI  - Delayed-onset multifocal polymicrobial keratitis after laser in situ
      keratomileusis.
AB  - We report a case of mixed Aspergillus fumigatus and coagulase-negative
      Staphylococcus stromal keratitis in a 43-year-old man who developed discomfort
      and swelling in his right eye 20 days after uneventful bilateral laser in situ
      keratomileusis (LASIK). Clinical examination revealed 2 distinct corneal
      infiltrates beneath the LASIK flap. Corneal scrapings were taken for microscopic
      examination and culture. Both infiltrates initially improved on topical
      antibiotic therapy, but over the next 18 days, 1 infiltrate worsened and repeat
      cultures were performed, which demonstrated A fumigatus. Natamycin 5% and
      amphotericin 0.1% were started and continued for 8 weeks with resolution of the
      infiltrate and return of the best corrected visual acuity. Delayed-onset
      multifocal keratitis is a rare complication of LASIK. Fungal entities should be
      considered in the differential diagnosis.

PMID- 11978477
TI  - Iris synechia after laser goniopuncture in a patient having deep sclerectomy with
      a collagen implant.
AB  - Neodymium:YAG (Nd:YAG) goniopuncture is an efficient and safe treatment for low
      filtration through the trabeculo-Descemet's membrane after deep sclerectomy with
      a collagen implant (DSCI). The only reported complication of this procedure is
      choroidal detachment. However, we found an iris synechia in a patient whose
      intraocular pressure (IOP) was elevated again 1 month after Nd:YAG goniopuncture.
      Synechiolysis and peripheral iridectomy with Nd:YAG and argon lasers effectively
      removed the iris synechia, and IOP immediately dropped to the normal range. We
      believe that iris synechia is a potential complication that may cause elevated
      IOP after laser goniopuncture in patients having DSCI.

PMID- 11978478
TI  - Total encapsulation and asymmetric deformation of an intraocular lens.
AB  - We report a case of marked anterior capsule contraction after uneventful cataract
      surgery in an 82-year-old women. The patient had implantation of a single-piece
      foldable acrylic intraocular lens (IOL) after phacoemulsification through a 3.0
      mm superior corneal incision. Between 1 month and 5.5 months after surgery,
      significant anterior capsule contraction ensued with total encapsulation of the
      lens. The resultant fibrotic reaction, which had a localized tangential
      component, caused an asymmetric deformation and mild IOL displacement. The
      patient was treated on separate occasions with a neodymium:YAG laser anterior
      capsulotomy and surgical capsulotomy to release tension on the lens and clear the
      visual axis.

PMID- 11978480
TI  - Carbonyl modified proteins in cellular regulation, aging, and disease.
AB  - The oxidative modification of proteins by reactive species is implicated in the
      etiology or progression of a panoply of disorders and diseases. The level of
      these modified molecules can be quantitated by measurement of the protein
      carbonyl content, which has been shown to increase in a variety of diseases and
      processes, notably during aging. For the most part, oxidatively modified proteins
      are not repaired and must be removed by proteolytic degradation, a process which
      normally proceeds very efficiently, from microorganisms to mammals. In
      eukaryotes, removal is usually carried out by the proteosome, which selectively
      degrades oxidatively modified proteins, whether they be damaged by reactive
      oxygen species or specifically oxidized by cellular regulatory processes. The
      molecular deficiencies that cause accumulation of oxidatively modified proteins
      are not identified, but regardless of cause, the accumulation is likely to
      disrupt normal cellular function.

PMID- 11978481
TI  - Oxidatively modified proteins in aging and disease.
AB  - There is a large body of evidence implicating oxidative damage in the
      pathogenesis of both normal aging and neurodegenerative diseases. Oxidative
      damage to proteins has been well established. Although there are a large number
      of potential oxidative modifications only a few have been systematically studied.
      The most frequently studied marker of oxidative damage to proteins is protein
      carbonyl groups. 3-Nitrotyrosine is thought to be a relatively specific marker of
      oxidative damage mediated by peroxynitrite. Increased concentrations of both
      protein carbonyls and 3-nitrotyrosine have been documented in both normal aging
      as well as in Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic
      lateral sclerosis (ALS). These findings help to provide a rationale for trials of
      antioxidants in neurodegenerative diseases.

PMID- 11978482
TI  - Repair of oxidative DNA damage in nuclear and mitochondrial DNA, and some changes
      with aging in mammalian cells.
AB  - Exposure to exogenous and endogenous sources cause oxidative damage to cellular
      macromolecules, including DNA. This results in gradual accumulation of oxidative
      DNA base lesions, and in order to maintain genomic stability we must have
      effective systems to repair this kind of damage. The accumulation of lesions is
      most dramatic in the mitochondrial DNA, and this may cause dysfunction and loss
      of cellular energy production. Base excision DNA repair (BER) is the major
      pathway that removes oxidative DNA base lesions, and while we know much about its
      mechanism in the nuclear DNA, little is yet known about this pathway in
      mitochondria. While nuclear BER decreases with age, the mitochondrial DNA repair
      may increase with age. This increase is not enough to prevent the gradual
      accumulation of lesions in the mitochondrial DNA with age. Accumulation of DNA
      lesions with age may be the underlying cause for age-associated diseases
      including cancer.

PMID- 11978483
TI  - Involvement of mammalian OGG1(MMH) in excision of the 8-hydroxyguanine residue in
      DNA.
AB  - 8-Hydroxyguanine (7,8-dihydro-8-oxoguanine, abbreviated as 8-OH-G or 8-oxoG) is
      the site of a frequent mutagenic DNA lesion produced by oxidative damage. MutM of
      E. coli and OGG1 of Saccharomyces cervisiae are known to possess 8-OH-G
      glycosylase and apurinic (AP) site lyase activity. cDNA clones of four isoforms
      (types 1a, 1b, 1c, and 2) of human OGG1 homologs (hMMH) were isolated. In order
      to examine whether expression of hMMH (hOGG1) protein actually occurs in human
      cells, we prepared type 1a specific antibody, and by using this antibody, we
      showed that type 1a protein isolated from HeLaS3 has 8-OH-G glycosylase/lyase
      activity. Furthermore, we showed that type 1a protein is a major enzyme for
      repair of the 8-OH-G lesion in human cells. In our second study, we generated a
      mouse line carrying an inactivated mutant Mmh allele by targeted gene disruption.
      Liver extracts of Mmh homozygous mutant mice were found to have loss of the
      nicking activity for the 8-OH-G site. In addition, the amount of endogenous 8-OH
      G in liver DNA of the homozygous mice increased linearly with age, reaching 7
      fold increase in 14 week old mice, over that of wild-type or heterozygous mice.
      Furthermore, when homozygous mice were fed the oxygen radical-forming agent
      KBrO3, to provide oxidative stress, the level of 8-OH-G in kidney DNA was
      tremendously increased: more than 200-fold as that of control mice without
      oxidative stress after 12 weeks of age. These results indicate that Ogg1/Mmh
      plays an essential role in the repair of the 8-OH-G residue in DNA produced by
      oxidative stress.

PMID- 11978484
TI  - The role of metals in site-specific DNA damage with reference to carcinogenesis.
AB  - We reviewed the mechanism of oxidative DNA damage with reference to metal
      carcinogenesis and metal-mediated chemical carcinogenesis. On the basis of the
      finding that chromium (VI) induced oxidative DNA damage in the presence of
      hydrogen peroxide (H2O2), we proposed the hypothesis that endogenous reactive
      oxygen species play a role in metal carcinogenesis. Since then, we have reported
      that various metal compounds, such as cobalt, nickel, and ferric
      nitrilotriacetate, directly cause site-specific DNA damage in the presence of
      H2O2. We also found that carcinogenic metals could cause DNA damage through
      indirect mechanisms. Certain nickel compounds induced oxidative DNA damage in rat
      lungs through inflammation. Endogenous metals, copper and iron, catalyzed ROS
      generation from various organic carcinogens, resulting in oxidative DNA damage.
      Polynuclear compounds, such as 4-aminobiphenyl and heterocyclic amines, appear to
      induce cancer mainly through DNA adduct formation, although their N-hydroxy and
      nitroso metabolites can also cause oxidative DNA damage. On the other hand,
      mononuclear compounds, such as benzene metabolites, caffeic acid, and o
      toluidine, should express their carcionogenicity through oxidative DNA damage.
      Metabolites of certain carcinogens efficiently caused oxidative DNA damage by
      forming NADH-dependent redox cycles. These findings suggest that metal-mediated
      oxidative DNA damage plays important roles in chemical carcinogenesis.

PMID- 11978485
TI  - Molecular bases of cellular iron toxicity.
AB  - Patients with hereditary or secondary hemochromatosis are liable to cardiac and
      hepatic failure, and type II diabetes. Despite the highly likely conjecture that
      iron-mediated tissue damage involves the conspiracy of cellular oxidizing and
      reducing equivalents, the pathophysiologic events have not been fully elucidated.
      These latter likely involve toxic effects of iron on intracellular organelles, in
      particular, mitochondria and lysosomes. The tissues at risk-heart, liver, and
      pancreatic beta cells-all have highly active mitochondria, which incidentally
      generate activated oxygen species capable of causing synergistic toxicity with
      intracellular iron. This suggests the general concept that iron may be
      preferentially toxic to cells with high mitochondrial activity. At least part of
      the long-term toxicity may involve iron-mediated oxidative damage to the
      mitochondrial genome with an accumulation of mutational events leading to
      progressive mitochondrial dysfunction. An alternative-and not mutually exclusive
      mechanism for cellular iron toxicity involves iron-catalyzed oxidative
      destabilization of lysosomes, leading to leak of digestive enzymes into the cell
      cytoplasm and eventuating in apoptotic or necrotic cell death.

PMID- 11978486
TI  - Nitrogen dioxide and carbonate radical anion: two emerging radicals in biology.
AB  - Nitrogen dioxide and carbonate radical anion have received sporadic attention
      thus far from biological investigators. However, accumulating data on the
      biochemical reactions of nitric oxide and its derived oxidants suggest that these
      radicals may play a role in various pathophysiological processes. These potential
      roles are also indicated by recent studies on the high efficiency of urate and
      nitroxides in protecting cells and whole animals against the injury associated
      with conditions of excessive nitric oxide production. The high protective effects
      of these antioxidants are incompletely defined at the mechanistic level but some
      of them can be explained by their efficiency in scavenging peroxynitrite-derived
      radicals, particularly nitrogen dioxide and carbonate radical anion. In this
      review, we provide a framework for this hypothesis and discuss the potential
      sources and properties of these radicals that are likely to become increasingly
      recognized as important mediators of biological processes.

PMID- 11978487
TI  - Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles
      of reactive oxygen species and cyclooxygenase.
AB  - There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a
      BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for
      platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet
      aggregation, with induction of thromboxane B2 (TXB2) production. Contrastingly,
      Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced
      platelet aggregation, and TXB2 and prostaglandin-D2 (PGD2) production. PBL
      extract also inhibited platelet TXB2 and PGD2 production triggered by thrombin,
      platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little
      effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O2(*-)
      and *OH, and inhibits xanthine oxidase activity and the (*)OH-induced PUC18 DNA
      breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
      (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB2
      production. Indomethacin, genistein, and PBL extract inhibited only TXB2
      production, but not platelet aggregation. Catalase, superoxide dismutase, and
      dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation,
      whereas catalase and DMT inhibited the AN-induced TXB2 production. These results
      suggest that AN-induced platelet aggregation is associated with iron-mediated
      reactive oxygen species production, calcium mobilization, phospholipase C
      activation, and TXB2 production. PBL inhibited platelet aggregation via both its
      antioxidative effects and effects on TXB2 and PGD2 production. Effects of AN and
      PBL on platelet aggregation and AA metabolism is crucial for platelet activation
      in the oral mucosa and cardiovascular system in BQ chewers.

PMID- 11978488
TI  - Nitroxides inhibit peroxyl radical-mediated DNA scission and enzyme inactivation.
AB  - Nitroxides are cell-permeable stable radicals that protect biomolecules from
      oxidative damage in several ways. The mechanisms of protection studied to date
      include removal of superoxide radicals as SOD-mimics, oxidation of transition
      metal ions to preempt the Fenton reaction, and scavenging carbon-centered
      radicals. However, there is no agreement regarding the reaction of piperidine
      nitroxides with peroxyl radicals. The question of whether they can protect by
      scavenging peroxyl radicals is important because these radicals are formed in the
      presence of oxygen abundant in biological tissues. To further our understanding
      of the antioxidative behavior of piperidine nitroxides, we studied their effect
      on biochemical systems exposed to the water soluble radical initiator 2,2'-azobis
      (2-amidinopropane) hydrochloride (AAPH). AAPH thermally decomposes to yield tert
      amidinopropane radicals (t-AP(*)) that readily react with oxygen to form peroxyl
      radicals (t-APOO(*)). It has recently been reported that piperidine nitroxides
      protect plasmid DNA from t-AP(*) though not from t-APOO(*). The present study was
      directed at the question of whether these nitroxides can protect biological
      systems from damage inflicted by peroxyl radicals. The reaction of nitroxides
      with AAPH-derived radicals was followed by cyclic voltammetry and electron
      paramagnetic resonance spectroscopy, whereas the accumulation of peroxide was
      iodometrically assayed. Assaying DNA damage in vitro, we demonstrate that
      piperidine nitroxides protect from both t-AP(*) and t-APOO(*). Similarly,
      nitroxides inhibit AAPH-induced enzyme inactivation. The results indicate that
      piperidine nitroxides protect the target molecule by reacting with and
      detoxifying peroxyl radicals.

PMID- 11978489
TI  - Influence of aging and long-term caloric restriction on oxygen radical generation
      and oxidative DNA damage in rat liver mitochondria.
AB  - The effect of long-term caloric restriction and aging on the rates of
      mitochondrial H2O2 production and oxygen consumption as well as on oxidative
      damage to nuclear (nDNA) and mitochondrial DNA (mtDNA) was studied in rat liver
      tissue. Long-term caloric restriction significantly decreased H2O2 production of
      rat liver mitochondria (47% reduction) and significantly reduced oxidative damage
      to mtDNA (46% reduction) with no changes in nDNA. The decrease in ROS production
      was located at complex I because it only took place with complex I-linked
      substrates (pyruvate/malate) but not with complex II-linked substrates
      (succinate). The mechanism responsible for that decrease in ROS production was
      not a decrease in mitochondrial oxygen consumption because it did not change
      after long-term restriction. Instead, the caloric restricted mitochondria
      released less ROS per unit electron flow, due to a decrease in the reduction
      degree of the complex I generator. On the other hand, increased ROS production
      with aging in state 3 was observed in succinate-supplemented mitochondria because
      old control animals were unable to suppress H2O2 production during the energy
      transition from state 4 to state 3. The levels of 8-oxodG in mtDNA increased with
      age in old animals and this increase was abolished by caloric restriction. These
      results support the idea that caloric restriction reduces the aging rate at least
      in part by decreasing the rate of mitochondrial ROS production and so, the rate
      of oxidative attack to biological macromolecules like mtDNA.

PMID- 11978490
TI  - Nuclear factor-kappaB mediates over-expression of cyclooxygenase-2 during
      activation of RAW 264.7 macrophages in selenium deficiency.
AB  - Selenium (Se) is an essential micronutrient for all mammalian species and is
      associated with a variety of physiological functions, notably immune system, in
      the form of selenoproteins. Inadequate Se nutrition has been linked to various
      diseases, including rheumatoid arthritis, cardiomyopathy, and cancer. Important
      to this discussion is that cyclooxygenase-2 (COX-2) is over-expressed in all the
      aforesaid pathologies; however, a casual relationship between Se status and COX-2
      expression remains to be established. The present study is based on the
      hypothesis that oxidant stress, a consequence of Se deficiency, lowers the
      activation potential of the redox-sensitive transcription factor, NF-kappaB, and
      that the activated NF-kappaB is required for the altered expression of COX-2. To
      test this hypothesis, we have investigated the relationship between Se status and
      COX-2 expression in response to LPS stimulation in RAW 264.7, a macrophage-like
      cell line. In Se-deficient cells, the Se-dependent glutathione peroxidase
      activity (Se-GPx), a measure of Se status, was markedly reduced and the overall
      oxidative stress was significantly higher than Se-supplemented cells. Upon
      lipopolysaccharide (LPS) stimulation, we found 2-3-folds higher COX-2 protein
      expression as well as higher PGE2 levels in Se-deficient cells than Se
      supplemented cells. In comparison, COX-1 protein expression was not affected by
      either LPS stimulation or Se status. Following LPS stimulation, the nuclear
      localization of NF-kappaB was significantly increased in Se-deficient
      macrophages, thereby leading to increased expression of COX-2. This is the first
      report demonstrating an inverse relationship between Se status and the expression
      of COX-2.

PMID- 11978491
TI  - Particle-induced oxidative damage is ameliorated by pulmonary antioxidants.
AB  - This investigation focuses on the application of an in vitro assay in elucidating
      the role of lung lining fluid antioxidants in the protection against inhaled
      particles, and to investigate the source of bioreactivity in urban PM10
      collections from South Wales. The Plasmid Assay is an in vitro method of
      assessing and comparing the oxidative bioreactivity of inhalable particles. This
      method has provided the basis of limited toxicological studies into various
      inhaled xenobiotics including asbestos, and more recently PM10. Carbon Black M120
      and Diesel Exhaust Particles (DEP) were tested as PM10 surrogates, DEP displaying
      the greatest oxidative bioreactivity. Both urban PM2.5 (fine fraction) and PM2.5
      10 (coarse fraction) (Cardiff, S. Wales, UK) caused significant damage, the
      coarse fraction displaying higher oxidative capacity. The soluble components were
      found to be responsible for most of the bioreactivity in both PM sizes. Low
      molecular components of fresh lung lavage were found to offer most antioxidant
      protection, and surrogate Epithelial Lining Fluid (sELF) showed significant
      amelioration of DNA damage by the coarse fraction but less effect against the
      fine. Overall, the coarse, soluble fraction of PM10 is a great source of
      oxidative bioreactivity, but natural pulmonary low molecular weight antioxidants
      can significantly ameliorate its effects.

PMID- 11978492
TI  - Oxidative stress in a phenylketonuria animal model.
AB  - Oxidative stress is seen in various metabolic disorders for unknown reasons.
      Oxidative stress is defined as an imbalance between pro-oxidant and antioxidant
      status in favor of the former. This study investigated whether oxidative stress
      exists in phenylketonuria (PKU) using the BTBR-Pah(enu2) animal model for PKU.
      Animals (14-24 weeks old) were sacrificed and brain and red blood cells (RBCs)
      were obtained aseptically. The lipid peroxidation by-product, evaluated as
      malondialdehyde (MDA), was significantly higher in the brains and RBCs of PKU
      animals (n = 6) than in controls (n = 6). Glutathione/glutathione disulfide, a
      good indicator for tissue thiol status, was significantly decreased both in the
      brains and RBCs. Some antioxidant enzymes were also analyzed in RBCs, including
      glucose-6-phosphate dehydrogenase (G6PD), which provides the RBC's main reducing
      power, reduced nicotinamide adenine dinucleotide phosphate (NADPH), and catalase
      detoxifies H2O2 by catalyzing its reduction to O2 and H2O. Both catalase and G6PD
      were significantly increased in the RBCs of PKU animals.

PMID- 11978493
TI  - Time window of nitroxide effect on myocardial ischemic-reperfusion injury
      potentiated by iron.
AB  - Transition metals such as iron and copper potentiate the postischemic reperfusion
      (I/R) injury induced by oxygen-derived radical and nonradical toxic species
      (ROS). Various natural and synthetic antioxidants have been previously tested to
      ameliorate such injury, yet the limitations of the common antioxidants are well
      known. An alternative strategy for combating oxidative damage is presented
      wherein cell-permeable, nitroxide stable radicals, which act as SOD-mimics and
      oxidize reduced metals thus prompting the Fenton-like chemistry, are investigated
      for utility in ameliorating I/R injury. Our study concentrates on the early
      effect of nitroxide on the myocardial I/R injury. Isolated rat hearts in the
      Langendorff configuration were equilibrated with Krebs-Henseleit buffer and then
      subjected to 18 min of normothermic global ischemia followed by 20 min
      reperfusion. Iron administered as Fe(III)-citrate (10 microM) did not affect the
      cardiac function under normoxia but did potentiate I/R injury and decreased the
      recovery during reperfusion. The iron-induced damage was manifested by further
      deterioration of the cardiac hemodynamic function and the energy status as
      reflected by decreased tissue level of phosphorylated nucleotides. Nitroxide at
      200 microM protected against the iron-potentiated I/R injury by improving the
      recovery of the hemodynamic function and the cardiac energy status. Exogenously
      added iron requires bioreduction to form deleterious Fe(II) bound to critical
      cellular sites. The nitroxide, which enters the cell and oxidizes the reduced
      metal instantaneously, provided protection even when administered 2 or 3.5, but
      not 5 min, after the onset of reperfusion. Thus, its narrow therapeutic time
      window provides insight into the schedule of the I/R injurious process.

PMID- 11978494
TI  - Reduced creatine kinase activity in transgenic amyotrophic lateral sclerosis
      mice.
AB  - Creatine (Cr), the substrate of the creatine kinase (CK) isoenzymes, was shown to
      be neuroprotective in several models of neurodegeneration, including amyotrophic
      lateral sclerosis (ALS). In order to investigate the mechanism of this beneficial
      effect, we determined CK activities and mitochondrial respiration rates in
      tissues from G93A transgenic mice, which overexpress a mutant form of human
      superoxide dismutase associated with familial ALS (FALS). While respiration rates
      of mitochondria from G93A transgenic or wild-type control mice isolated from
      spinal cord showed no difference, a significant and dramatic loss of CK activity
      could be detected in these tissues. In homogenates from spinal cord of G93A
      transgenic mice, CK activity decreased to 49% and in mitochondrial fractions to
      67% compared to CK activities in wild-type control mice. Feeding the G93A
      transgenic mice with 2% Cr, the same tissues showed no statistically significant
      increase of CK activity compared to regular fed G93A transgenic mice. Experiments
      with isolated mitochondria, however, showed that Cr and adenosine triphosphate
      (ATP) protected mitochondrial CK activity against peroxynitrite-induced
      inactivation, which may play a role in tissue damage in neurodegeneration. Our
      data provide evidence for oxidative damage to the CK system in ALS, which may
      contribute to impaired energy metabolism and neurodegeneration.

PMID- 11978495
TI  - Methionine oxidation as a major cause of the functional impairment of oxidized
      actin.
AB  - A significant specific increase in the actin carbonyl content has been recently
      demonstrated in human brain regions severely affected by the Alzheimer's disease
      pathology, in postischemic isolated rat hearts, and in human intestinal cell
      monolayers following incubation with hypochlorous acid (HOCl). We have very
      recently shown that exposure of actin to HOCl results in the immediate loss of
      Cys-374 thiol, oxidation of some methionine residues, and, at higher molar ratios
      of oxidant to protein, increase in protein carbonyl groups, associated with
      filament disruption and inhibition of filament formation. In the present work, we
      have studied the effect of methionine oxidation induced by chloramine-T (CT),
      which at neutral or slightly alkaline pH oxidizes preferentially Met and Cys
      residues, on actin filament formation and stability utilizing actin blocked at
      Cys-374. Methionines at positions 44, 47, and 355, which are the most solvent
      exposed methionyl residues in the actin molecule, were found to be the most
      susceptible to oxidation to the sulfoxide derivative. Met-176, Met-190, Met-227,
      and Met-269 are the other sites of the oxidative modification. The increase in
      fluorescence associated with the binding of 8-anilino-1-naphtalene sulfonic acid
      to hydrophobic regions of the protein reveals that actin surface hydrophobicity
      increases with oxidation, indicating changes in protein conformation. Structural
      alterations were confirmed by the decreased susceptibility to proteolysis and by
      urea denaturation curves. Oxidation of some critical methionines (those at
      positions 176, 190, and 269) causes a complete inhibition of actin polymerization
      and severely affects the stability of actin filaments, which rapidly
      depolymerize. The present results would indicate that the oxidation of some
      critical methionines disrupts specific noncovalent interactions that normally
      stabilize the structure of actin filaments. We suggest that the process involving
      formation of actin carbonyl derivatives would occur at an extent of oxidative
      insult higher than that causing the oxidation of some critical methionine
      residues. Therefore, methionine oxidation could be a damaging event preceding the
      appearance of carbonyl groups on actin and a major cause for the functional
      impairment of the carbonylated protein recently observed both in vivo and in
      vitro.

PMID- 11978496
TI  - Crocidolite asbestos inhibits pentose phosphate oxidative pathway and glucose 6
      phosphate dehydrogenase activity in human lung epithelial cells.
AB  - The cytotoxicity of asbestos has been related to its ability to increase the
      production of reactive oxygen species (ROS), via the iron-catalyzed reduction of
      oxygen and/or the activation of NADPH oxidase. The pentose phosphate pathway
      (PPP) is generally activated by the cell exposure to oxidant molecules. Contrary
      to our expectations, asbestos (crocidolite) fibers caused a dose- and time
      dependent inhibition of PPP and decreased its activation by an oxidative stress
      in human lung epithelial cells A549. In parallel, the intracellular activity of
      the PPP rate-limiting enzyme, glucose 6-phosphate dehydrogenase (G6PD), was
      significantly diminished by crocidolite exposure. This inhibition was selective,
      as the activity of other PPP and glycolysis enzymes was not modified, and was not
      attributable to a decreased expression of G6PD. On the opposite, the incubation
      with glass fibers MMVF10 did not modify PPP and G6PD activity. PPP and G6PD
      inhibition did not correlate with the increased nitric oxide (NO) production
      elicited by crocidolite in A549 cells. Experiments with the purified enzyme
      suggest that crocidolite inhibits G6PD by directly interacting with the protein.
      We propose here a new mechanism of asbestos-evoked oxidative stress, wherein
      fibers increase the intracellular ROS levels also by inhibiting the main
      antioxidant pathway of the cell.

PMID- 11978497
TI  - Animal model pharmacokinetics and pharmacodynamics: a critical review.
AB  - Animals have been extensively used in the evaluation of antimicrobials. The value
      of animals in the pharmacokinetic and pharmacodynamic characterization of
      antimicrobials is critically reviewed. Animal studies have demonstrated that the
      pharmacokinetic/pharmacodynamic (PK/PD) target determining efficacy can vary for
      different classes of antimicrobials. However, the magnitude of the target
      required for bacteriological efficacy is relatively similar for various sites of
      infection, various pathogens and various drugs within the same class, provided
      free drug levels are used.

PMID- 11978498
TI  - Rational dosing of antimicrobial drugs: animals versus humans.
AB  - The rational dosing of antimicrobial drugs depends on knowledge of physiology,
      anatomy and pathology, including disease condition, and in major respects these
      differ between animals and humans and between species of animal. These
      differences lead to species variation in drug pharmacokinetics, which can be
      profound. This review highlights selected aspects of species differences in
      pharmacokinetics and considers underlying mechanisms by reference to ruminant and
      non-ruminant mammals, birds, fish and bees. For all species it is desirable and
      should be possible to design dosage schedules based on knowledge of drug
      pharmacokinetics and pharmacodynamics. There have been many attempts to integrate
      pharmacokinetic and pharmacodynamic data to provide dosage schedules which
      optimize efficacy and minimize opportunities for the development of antimicrobial
      resistance in both laboratory animal studies and human clinical trials. However,
      there have been relatively few studies in animal species of major veterinary
      interest. This review summarizes recent studies in four ruminant species (calf,
      sheep, goat and camel) which have used PK-PD integration to determine for the
      fluoroquinolone, danofloxacin, AUC/MIC ratios producing (a) bacteriostasis (b)
      bactericidal activity and (c) elimination of bacteria. Future possible
      developments in dosage schedule design are considered.

PMID- 11978499
TI  - Rational dosing of antibiotics: the use of plasma concentrations versus tissue
      concentrations.
AB  - At the moment, the most common pharmacokinetic/pharmacodynamic (PK/PD) approaches
      for anti-infective agents, such as time above MIC, C(max)/MIC and AUC(24)/MIC,
      rely on plasma concentration as the PK input value and minimum inhibitory
      concentration (MIC) as the PD input value. However, only the free tissue
      concentrations of antibiotics at the target site are responsible for the
      therapeutic effect. Using plasma concentrations frequently overestimates the
      target site concentrations and therefore clinical efficacy. Microdialysis is a
      new technique that allows direct measurement of unbound tissue concentrations.
      Furthermore, a better PD approach, bacterial time-kill curves, can offer more
      detailed information about the antibacterial activity as a function of time and
      antibiotic concentration than MICs.

PMID- 11978500
TI  - Developments in PK/PD: optimising efficacy and prevention of resistance. A
      critical review of PK/PD in in vitro models.
AB  - In vitro pharmacokinetic models are excellent tools with which to study an
      antibacterial's pharmacodynamics (pD), being flexible, adaptable, low cost, and
      correlating well with animal and human systems. They can be used to perform
      simple descriptive studies on antibacterial effect, determine the dominant pD
      factor and its magnitude for antibacterial effect, and finally be used to assess
      the effect of dosing on emergence of resistance. A wide range of model designs
      are used and some standardisation maybe of value in the near future, however it
      is clear that in vitro models in conjunction with animal studies and human trials
      offer an excellent way of studying drug dosing to optimise outcomes.

PMID- 11978501
TI  - Long-circulating sterically stabilized liposomes as carriers of agents for
      treatment of infection or for imaging infectious foci.
AB  - Liposomes are considered as potential carriers for biologically active compounds.
      One evident drawback of 'classical' liposomes is their fast elimination by cells
      of the mononuclear phagocyte system (MPS), primarily by liver and spleen. An
      important breakthrough in this respect is the development of long-circulating
      liposomes among which liposomes coated with polyethyleneglycol (PEG), the so
      called 'sterically stabilized' liposomes (SSL). An important characteristic of
      SSL is that their prolonged blood residence time and infectious target
      localization is relatively independent of the lipid dose, particle size or lipid
      composition of the bilayer. SSL are applied as carriers of antimicrobial agents
      to achieve infectious target localization, to reduce side effects, or to serve as
      a micro-reservoir in the circulation. In addition, radiolabelled SSL are used to
      image infectious and inflammatory foci.

PMID- 11978502
TI  - The application of population pharmacokinetic modeling to individualized
      antibiotic therapy.
AB  - This paper describes applications of population pharmacokinetic modeling to the
      optimization of antibiotic dosing. Parametric and nonparametric pharmacokinetic
      modeling approaches are discussed. Population models can be important extensions
      of therapeutic drug monitoring (TDM) in infectious disease. The concept of
      population model-based individualized antimicrobial therapy is described. With
      the availability of population modeling for obtaining PK parameter estimates, the
      focus has shifted to quantifying the antimicrobial effect and linking kinetics to
      drug effects. Examples of integrated pharmacokinetic-pharmacodynamic (PK-PD)
      models to describe bacterial killing as a function of drug concentration are
      discussed. Application of PK-PD mathematical models that correlate with
      microbiological and clinical outcomes will provide us with a better rationale for
      the proper dose selection of anti-infective therapy in different patient
      populations.

PMID- 11978503
TI  - Breakpoints: current practice and future perspectives.
AB  - Much of the discussion over the past decades on the value and setting of
      breakpoints has been due to the fact that the breakpoint was used in two ways; as
      an indicator to predict the probability of clinical success and also to detect
      resistant (sub) populations. It is apparent that these two meanings have lead to
      a different approach to setting, interpretation and use of breakpoints based on
      clinical efficacy on the one hand and breakpoints based on detection of
      resistance on the other. Nevertheless, several of the current guidelines make no
      perceptible distinction between these two meanings. A case is therefore strongly
      made to recognize that there is a difference between clinical and microbiological
      breakpoints. The microbiological breakpoint may be used to detect organisms that
      do not belong to the natural bacterial population, but somehow have acquired
      resistance and might be useful in recognizing emergence of resistant
      subpopulations and may lead to subsequent measures to be taken. Alternatively,
      the clinical breakpoint is of principal value to the clinician in that it results
      in a classification of S (susceptible), I (intermediate susceptible) and R
      (resistant) and is used in clinical practice and correlate with a measure of
      clinical efficacy. Methods developed during the last few years to arrive at
      meaningful clinical breakpoints are discussed, such as CART analysis and Monte
      Carlo simulation. In discussing future developments, it is suggested that current
      reports containing S, I, and R be at least supplemented with the MICs measured
      and, using current techniques available such as Monte Carlo simulation, provide
      the probability of successful eradication of the micro-organism and successful
      treatment based on population pharmacokinetics and Minimal Inhibitory
      Concentration (MIC) distributions.

PMID- 11978504
TI  - How predictive is PK/PD for antibacterial agents?
AB  - The pharmacodynamic (PD) parameters most often used in studies of antibiotic
      effect include the following relationships between the antibiotic concentration
      curve in serum as a surrogate marker for the antibiotic concentration at the
      infection site, the peak/minimal inhibitory concentration (MIC) ratio, the area
      under the curve (AUC)/MIC ratio and the duration of time the concentration
      exceeds the MIC (T(>MIC)). The MIC plays an important role also as a PD marker,
      and its precision in this respect is discussed. The predictive role of T(>MIC) is
      important for drugs showing minimal concentration dependent effect such as the
      beta-lactam antibiotics, the macrolides and others. The time can be calculated as
      the chronological time measured or as the (cumulative) per cent of the dosing
      interval covered by the dose. Several clinical studies have confirmed this
      relationship. It can be deduced from experimental as well as clinical studies
      that there is a minimal effective time (MET), which needs to be covered by the
      antibiotic concentration at the site of infection in order to achieve cure.
      Dosing according to this MET will result in the least antibiotic needed for the
      shortest duration. In several cases a single dose will suffice to cover the MET.
      If this is not possible the antibiotic should be dosed in a way, that each dose
      will surpass the MIC for at least 40-50% of the dosing interval. For antibiotics
      with a clear concentration-dependent bacterial killing effect the most important
      pharmacokinetic/pharmacodynamic (PK/PD) index is the peak/MIC ratio (or the
      AUC/MIC ratio). This is the case for aminoglycosides and fluoroquinolones, and
      for both classes a peak/MIC ratio of at least 10 within the first 24 h of
      treatment has been shown to result in around 90% bacteriological as well as
      clinical cure. One consequence of clinical dosing has been the once-a-day (OD)
      dosing for aminoglycosides, which is the standard mode of therapy in many
      countries. Clinical studies in the field of antibacterial PD are still relatively
      scarce, and much information is needed to enable relevant dosing strategies for
      all types of antibiotics against all common infections and micro-organisms.

PMID- 11978505
TI  - Extended interval aminoglycoside dosing: from concept to clinic.
AB  - Extended-interval aminoglycoside dosing (EIAD), while a relatively recent concept
      in mainstream clinical practice, actually has its roots in the mid 1970s. Early
      trial and error approaches of manipulating the dosage regimen to avoid toxicity
      and improve efficacy have helped to characterize the pharmacodynamic properties
      of these drugs. The increasing successful use of EIAD and improved understanding
      of pharmacodynamics has helped this dosing regimen gain acceptance into routine
      clinical practice. A 1998 United States survey demonstrated that approximately
      75% of hospitals have adopted EIAD into routine patient care. However,
      controversy still exists regarding some aspects of infrequent aminoglycoside
      administration, such as length of the drug-free interval and patient exclusion
      criteria. After more than 50 years of experience with the aminoglycosides we
      continue to learn how to most appropriately use these drugs.

PMID- 11978506
TI  - Can PK/PD be used in everyday clinical practice.
AB  - Over the last decade much insight has been gained in the relationships between
      dosing regimens of antimicrobials and bacterial eradication and clinical
      efficacy. These pharmacokinetic-pharmacodynamic (PK/PD) relationships have become
      available as tools in individualising antimicrobial therapy. To be able to do
      this, the PK parameters of the antimicrobial in the individual patient have to be
      known or estimated, and the MIC of the micro-organism causing the infection,
      known. In our hospital, we have started a programme using this approach.
      Preliminary results suggest that dose optimisation leads to increased efficacy
      and lower costs.

PMID- 11978507
TI  - Standardization of pharmacokinetic/pharmacodynamic (PK/PD) terminology for anti
      infective drugs.
AB  - Over the last decades, the interest in the relationships between the
      pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents has
      increased and, therefore, the use of PK/PD indices and expressions has spread
      widely. The appropriate definition and use of these parameters is a matter of
      controversy. This paper contains a proposal to use PK/PD expressions for
      antimicrobial agents and their units in a uniform manner.

PMID- 11978508
TI  - Past, present and future perspectives of colorectal cancer--on the brink of a new
      era?

PMID- 11978509
TI  - Distinction between familial and sporadic forms of colorectal cancer showing DNA
      microsatellite instability.
AB  - Attempts to classify colorectal cancer into subtypes based upon molecular
      characterisation are overshadowed by the classical stepwise model in which the
      adenoma-carcinoma sequence serves as the morphological counterpart. Clarity is
      achieved when cancers showing DNA microsatellite instability (MSI) are
      distinguished as sporadic MSI-low (MSI-L), sporadic MSI-high (MSI-H) and
      hereditary non-polyposis colorectal cancer (HNPCC). Divergence of the
      'methylator' pathway into MSI-L and MSI-H is at least partly determined by the
      respective silencing of MGMT and hMLH1. Multiple differences can be demonstrated
      between sporadic and familial (HNPCC) MSI-H colorectal cancer with respect to
      early mechanisms, evolution, molecular characterisation, demographics and
      morphology. By acknowledging the existence of multiple pathways, rapid advances
      in the fields of basic and translational research will occur and this will lead
      to improved strategies for the prevention, early detection and treatment of
      colorectal cancer.

PMID- 11978510
TI  - The APC gene in colorectal cancer.
AB  - Mutations in the adenomatous polyposis coli (APC) gene are not only responsible
      for familial adenomatous polyposis (FAP), but also play a rate-limiting role in
      the majority of sporadic colorectal cancers. Colorectal tumours are known to
      arise through a gradual series of histological changes, the so-called 'adenoma
      carcinoma' sequence, each accompanied by a genetic alteration in a specific
      oncogene or tumour suppressor gene. Loss of APC function triggers this chain of
      molecular and histological changes. In general, an intestinal cell needs to
      comply with two essential requirements to develop into a cancer: it must acquire
      selective advantage to allow for the initial clonal expansion, and genetic
      instability to allow for multiple hits at other genes responsible for tumour
      progression and malignant transformation. Inactivation of APC seems to fulfill
      both requirements. In this short review, I will discuss the role played by APC in
      providing, when mutated, selective advantage, through constitutional activation
      of the Wnt signal transduction pathway, and chromosomal instability to the
      nascent intestinal tumor cell.

PMID- 11978511
TI  - Cancer genetics and their application to individualised medicine.
AB  - One of the great challenges of basic research is to translate scientific
      discoveries into the improved treatment of patients. For colorectal cancer, our
      increased understanding of the molecular aetiology of the disease has not yet
      been paralleled by an improvement in patient care. However, several new
      approaches are on the verge of clinical implementation. Technical advances such
      as real-time polymerase chain reaction (PCR) and microarray techniques coupled to
      insight in the molecular pathways in colorectal cancer makes it possible to
      develop new clinical tools for the diagnosis, classification and treatment of
      patients. The ultimate goal of the incorporation of cancer genetics into the
      clinical treatment of patients is individualised medicine; therapeutic strategies
      based on the molecular taxonomy of tumours and individually constructed for each
      patient.

PMID- 11978512
TI  - Prognosis and response to therapy in colorectal cancer.
AB  - Colorectal cancer is Europe's second biggest cancer killer. Yet despite advances
      in knowledge and changes in chemotherapy practice, we have not seen great strides
      in improved survival. Histopathological staging is at present the most accurate
      prognostic factor for survival and recurrence. Improvements in staging have led
      to the recognition of the importance of the circumferential resection margin
      (CRM) and how the quality of surgery influences local recurrence rates. Further
      refinements in staging and increasing knowledge of tumour biology will have a
      large contribution to play in the future.

PMID- 11978513
TI  - Radiology of colorectal cancer.
AB  - In the past 20 years, the radiology of colorectal cancer has evolved from the
      barium enema to advanced imaging modalities like phased array magnetic resonance
      imaging (MRI), virtual colonoscopy and positron emission tomography (PET).
      Nowadays, primary rectal cancers are preferably imaged with transrectal
      ultrasound or MRI, while barium enema is still the most often used technique for
      imaging of colonic cancers. Virtual colonoscopy is rapidly evolving and might
      considerably change the imaging of colorectal cancer in the near future. The use
      of virtual colonoscopy for screening purposes and imaging of the colon in
      occlusive cancer or incomplete colonoscopies is currently under evaluation. The
      main role of PET is in detecting tumour recurrences, both locally and distantly.
      Techniques to fuse cross-sectional anatomical (computer tomography (CT) and MRI)
      and functional (PET) images are being developed. Apart from diagnostic imaging,
      the radiologists has added image-guided minimally invasive treatments of
      colorectal liver metastases to their arsenal. The radio-frequency ablation
      technique is now widely available, and can be used during laparotomy or
      percutaneously in selected cases.

PMID- 11978514
TI  - Laparoscopic surgery for colorectal carcinoma. an overnight victory?
AB  - Laparoscopic surgery became popular in the early 1990s. Cholecystectomy was the
      first 'victim' conquered by the new technique and laparoscopic cholecystectomy
      became the gold standard operation for gallbladder stones. Laparoscopic
      colorectal surgery was then attempted, for both benign and malignant disorders.
      After a short period of enthusiasm, alarming reports were published on
      laparoscopic surgery for malignant disease. The occurrence of so called 'port
      site' metastases (PSM) led to a reduction in the use of the minimal invasive
      technique. In addition, the duration of the operations was criticised, as well as
      the limited beneficial effects (if any) and the possible violation of oncological
      surgical principles. The pros and cons of this new technique during its
      introduction are discussed, with focus on problem areas such as port-site
      metastases, surgical learning curve as well as beneficial effects. The current
      status of several comparative studies evaluating the laparoscopic technique is
      discussed leading to the conclusion that a basis for further research exists and
      therefore cautious progress is warranted.

PMID- 11978515
TI  - Transanal endoscopic microsurgery for rectal cancer.
AB  - If curation is intended for rectal cancer, total mesorectal excision with
      autonomic nerve preservation (TME) is the gold standard. Transanal resection is
      tempting because of low mortality and morbidity rates. However, inferior tumour
      control, provoked by the limitations of the technique, resulted in its cautious
      application and use mainly for palliation. Transanal endoscopic microsurgery
      (TEM) is a minimal invasive technique for the local resection of rectal tumours.
      It is a one-port system, introduced transanally. An optical system with a 3D
      view, 6-fold magnification and resolution as the human eye, together with the
      creation of a stabile pneumorectum, and specially designed instruments allow full
      thickness excision under excellent view and a proper histological examination.
      The technique can also be applied for larger and more proximal tumours.
      Mortality, morbidity as well as incomplete excision rates are minimal. Local
      recurrence and survival rates seem comparable to TME in early rectal cancer. TEM
      is the method of choice when local resection of rectal cancer is indicated.
      Results justify a re-evaluation of the indications for the local excision of
      rectal cancer with a curative intent.

PMID- 11978516
TI  - Patterns of lymphatic spread in rectal cancer. A topographical analysis on lymph
      node metastases.
AB  - The presence of lymph node (LN) metastases is the most important prognostic
      factor in rectal cancer. The exact LN status can only be known when an extended
      lymph node dissection (LND) has been performed, a process not routinely
      performed. If the likelihood of LN metastases can be more accurately assessed
      preoperatively, then an optimal multimodality treatment plan can be established.
      605 patients with primary rectal cancer operated upon with wide LND (D3 level)
      were analysed for LN metastases combining topographical localisation and
      morphological features of the tumour. More distal rectal tumours tend to more LN
      metastases and more lateral lymphatic spread. Tumours >or=3 cm show more LN
      metastases compared with those smaller than 3 cm. Depth of bowel wall invasion is
      strongly related to the presence of LN metastases. The peritoneal reflection has
      no discriminating role in the mode of spread. Intra-operative assessment by the
      surgeon for presence of LN metastases is not reliable. When localisation, depth
      of bowel wall invasion and diameter of a rectal tumour are known, a likelihood of
      LN metastases can be assessed pre-operatively, not intra-operatively.

PMID- 11978517
TI  - Developments and quality assurance in rectal cancer surgery.
AB  - One of the main problems in the treatment of rectal cancer is the development of
      local recurrences. In the last decades, major improvements have been realized in
      the surgical treatment of rectal cancer. The introduction of TME-surgery has led
      to a large reduction in local recurrence rates and improved survival. TME-based
      operations are now established as the standard of care for rectal cancer, and
      should form the basis for trials concerning the role of (neo)adjuvant therapy.
      However, training and quality control are prerequisites to obtain good results in
      all surgeons' hands. Furthermore, standardization in the description of
      operations and reporting of pathology specimens should be implemented as
      important features of quality control. In general, it is thought that high volume
      and specialist care produces superior results to low volume and non-specialist
      care, especially for those less frequent forms of cancer and in technically
      difficult operations, like those for rectal cancer. However, limiting the
      performance of rectal cancer surgery to highly specialized surgeons or to only
      those general surgeons who perform more than a certain volume is impractical in
      view of the prevalence of rectal cancer. This article reviews developments in the
      treatment of especially mobile rectal cancer and pays attention to variability in
      outcomes and quality assurance of surgery.

PMID- 11978518
TI  - Surgical trials in oncology. the importance of quality control in the TME trial.
AB  - Results from randomised trials provide the best scientific evidence of efficacy
      or inefficacy of the therapy. The evaluation of surgical procedures involves
      problems in addition to those associated with medical experimentation. Surgery,
      unlike a pill, is not a standardised, reproducible entity, but a unique product
      whose details are defined by, for example, the skill of the surgeon. Quality
      assurance is important for treatment and also for data handling. The different
      treatments (surgery, pathology, radiotherapy, etc.) should be familiar to all
      participating physicians prior to the start of the trial. Instructions can be
      given by means of a well-written protocol, videotapes, workshops and instructors
      at the dissection table. The data collection and data check should be done by
      data managers and co-ordinators for the separate disciplines. Errors and missing
      data should be completed and feedback to the physician is essential. Close
      contact between an active co-ordinating data centre, including co-ordinators for
      the separate disciplines, and all participating physicians is essential to
      conduct a quality controlled multicentre, multidisciplinary trial. Continuous
      enthusiasm can be maintained by the organisation of regular workshops,
      distribution of newsletters and trial up-dates at scientific meetings. The
      efforts from all of the involved co-ordinators, data managers, instructors and
      physicians have resulted in a very successful trial with rapid accrual, good
      quality treatments and procedures, good quality data, and a high participation
      rate among hospitals and patients. Quality control is expensive and labour
      intensive, but it is worthwhile.

PMID- 11978519
TI  - The role of radiotherapy in rectal cancer.
AB  - In Europe, short-term radiotherapy is increasingly used in the primary management
      of rectal cancer. In the United States, postoperative chemoradiotherapy is the
      standard treatment of choice. The rationale and indications for radiotherapy and
      possible combinations with chemotherapy are discussed and an overview of all of
      the randomised trials containing radiotherapy as one randomisation arm is given.
      Three major indications for radiotherapy can be identified: the reduction of
      local recurrences in mobile rectal cancer, downstaging of the tumour in primary
      irresectable tumours and downsizing of low-lying tumours in attempts to more
      frequently perform a sphincter-saving procedure. For reduction of local
      recurrences, radiotherapy can be given either pre- or postoperatively, although
      preoperative therapy is more dose-efficient. Short-term preoperative radiotherapy
      reduces the number of recurrences and improves survival. Improved survival is
      also reported after postoperative radiotherapy in combination with chemotherapy,
      however, the relevance of the radiotherapy component is discussed. Although the
      debate about radiotherapy is still ongoing, we strongly believe that the results
      demonstrate that short-term preoperative radiotherapy is the treatment of choice
      for resectable rectal cancer.

PMID- 11978520
TI  - Cost-effectiveness analysis of colorectal cancer treatments.
AB  - A concise overview is provided of the methodology of cost-effectiveness analyses,
      followed by a survey of published CEAs of colorectal cancer treatments. To gain
      credibility, the methodology applied in CEAs must be further improved. Costs are
      rarely estimated from the societal perspective, and little is known about how
      colorectal patients value their treatment and health.

PMID- 11978521
TI  - The role of pathologists in the quality control of diagnosis and treatment of
      rectal cancer-an overview.
AB  - Pathological examination of the rectal cancer resection specimen has an
      increasingly important role in influencing decisions about clinical management.
      Standardisation of the examination procedures and reporting are necessary. To
      evaluate the relevant pathological factors, data from randomised clinical trials
      with adequate follow-up are necessary. From a recently closed trial on the
      treatment of rectal cancer (preoperative radiotherapy or total mesorectal
      excision (TME) surgery alone?), the pathological data were used to evaluate the
      importance of pathological factors, like circumferential margin and tumour, lymph
      nodes, metastasis (TNM) stage. Furthermore, it was possible to evaluate the
      surgical procedures and correlate these findings to clinically relevant
      endpoints. In this review, we describe the standard evaluation of a rectal cancer
      specimen with special attention to preoperative irradiated specimens.

PMID- 11978522
TI  - The circumferential margin in rectal cancer. Recommendations based on the Dutch
      Total Mesorectal Excision Study.
AB  - A very low local recurrence rate in rectal cancer is possible with optimal
      staging, preoperative radiotherapy and the use of total mesorectal excision
      (TME). Data from a study where patients were randomised for preoperative
      radiotherapy (or not) and complete removal of the tumour and mesorectum were
      examined. A consensus meeting was held to discuss the data in which the following
      guidelines for implementation were made. Adequate imaging is necessary to
      increase the likelihood of a R0 resection. Advances cases (possible margin to the
      endopelvicfascie less than 2 mm) need a long course of preoperative radiotherapy.
      Primary resectable cases benefit from a short course of radiation directly
      followed by surgery. A continuous quality control of surgery is mandatory in
      order to maintain the skill for a TME. A complete pathology report is important
      for the quality control of the surgical treatment and to predict the outcome of
      treatment. All of the involved disciplines in the diagnosis and treatment of
      rectal cancer should focus on the circumferential margin to guide for optimal
      treatment. Multidisciplinary teams are important for the achievement of optimal
      treatment planning of rectal cancer patients and maintenance of the highest level
      of quality control.

PMID- 11978523
TI  - Ultrastaging of early colon cancer using lymphatic mapping and molecular
      analysis.
AB  - Approximately one-third of node-negative colon cancers will recur, possibly due
      to understaging and inadequate pathological examination of lymph nodes (LNs). We
      evaluated the sensitivity, accuracy and feasibility of staging based on lymphatic
      mapping, focused examination, and molecular analysis of the sentinel node (SN) in
      patients with primary colorectal carcinoma. Between 1996 and 2000, 100 patients
      with colon carcinoma (CRC) underwent lymphatic mapping immediately after
      peritumoral injection of 1.0 cc of isosulphan blue dye. All LNs in the CRC
      specimen were examined by routine haematoxylin and eosin (H&E) staining. Sentinel
      nodes were examined by step serial sectioning, cytokeratin immunohistochemistry
      (CK-IHC) and/or reverse transcriptase-polymerase chain reaction (RT-PCR) analysis
      in an attempt to identify occult micrometastatic disease. Lymphatic mapping was
      successful in 97% of the cases. There were 5 false-negative cases, predominately
      associated with T3/T4 tumours. Aberrant lymphatic drainage was identified in 8
      patients (8%) altering the operative approach. 26 patients had H&E-positive LNs.
      In 74 patients who were node-negative by routine H&E, 18 (24%) had occult nodal
      micrometastases missed on routine H&E examination, but detected by focused
      analysis of the SN. RT-PCR analysis of the SN was performed in 40 patients, 26 of
      which were negative by H&E and CK-IHC. In 12/26 (46%) of these patients, there
      was additional evidence of micrometastatic disease. In this study, focused
      examination of the SN in conjunction with RT-PCR analysis identified
      micrometastatic disease in a significant number of node-negative patients. This
      may have important implications when selecting patients for adjuvant treatment
      protocols.

PMID- 11978524
TI  - Follow-up of patients with colorectal cancer: numbers needed to test and treat.
AB  - Follow-up after curative treatment of patients with colorectal cancer has as its
      main aims the quality assessment of the treatment given, patient support, and
      improved outcome by the early detection and treatment of cancer recurrence. How
      often, and to what extent, the final aim, improved survival, is indeed realised
      is so far unclear. A literature search was performed to provide quantitative
      estimates for the main determinants of the effectiveness of the follow-up. Data
      were extracted from a total of 267 articles and databases, and were aggregated
      using modern meta-analytic methods. In order to provide one more colorectal
      cancer patient with long-term survival through follow-up, 360 positive follow-up
      tests and 11 operations for colorectal cancer recurrence are needed. In the
      remaining 359 tests and 10 operations, either no gains are achieved or harm is
      done. As the third aim of colorectal cancer follow-up, improved survival, is
      realised in only few patients, follow-up should focus less on diagnosis and
      treatment of recurrences. It should be of limited intensity and duration (3
      years), and the search for preclinical cancer recurrence should primarily be
      performed by carcino-embryonic antigen (CEA) testing and ultrasound (US). The
      focus of colorectal cancer follow-up should shift from the early detection of
      recurrence towards quality assessment and patient support. As support that is as
      good or even better can be provided by a patient's general practitioner (GP) or
      by specialised nursing personnel, there is no need for routine follow-up to be
      performed by the surgeon.

PMID- 11978525
TI  - Systemic treatment of colorectal cancer.
AB  - Palliative and adjuvant treatment for colorectal cancer has been, until recently,
      largely dependent on 5-fluorouracil (5-FU)-based chemotherapy. Oral
      fluoropyrimidines have been evaluated in the advanced disease setting and they
      appear to be as effective as 5-FU, but are safer and more convenient for most
      patients. Irinotecan and oxaliplatin are new cytotoxic agents, which are active
      in 5-FU-resistant disease, but which may also be combined with 5-FU as initial
      therapy in advanced disease. Initial combination therapy leads to improved
      response rates and more prolonged progression-free survival compared with 5-FU
      monotherapy. Standard regimens for adjuvant therapy usually involve 6 months of
      chemotherapy using 5-FU and folinic acid. Recent trials of capecitabine,
      oxaliplatin and irinotecan in the adjuvant setting are ongoing, or have recently
      completed accrual, and may lead to a change in future clinical practice.
      Biological therapies are playing an increasing role in the management of
      colorectal cancer. Farnesyl transferase inhibition, inhibition of the epidermal
      growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF)
      are undergoing evaluation in advanced disease. In the adjuvant setting, both
      passive and active immunotherapeutic approaches have been studied. In addition, a
      large trial will evaluate the role of cyclo-oxygenase(COX)-2 inhibitors as
      adjuvant therapy. Further research is required in order to define the optimal
      sequence and combination of these different cytotoxic and biological therapies,
      in order to secure the best possible outcome for various subgroups of patients
      with both early and advanced stage colorectal cancer.

PMID- 11978526
TI  - Biological therapy of colorectal cancer.
AB  - In this review, the immunogenicity of colorectal cancer (CRC) and the results of
      clinical and recent preclinical studies are discussed. Evidence for immune
      reactivity has been found in several preclinical models and the prognostic value
      of some of these immune responses have been reported. The possible mechanisms are
      discussed. Treatment with monoclonal antibodies is still experimental; as
      previously described benefit of treatment with monoclonal antibodies could not be
      confirmed. Labelled monoclonal antibody therapy has produced mixed results and
      also need further investigation. Several antigens are used in active specific
      immunotherapy (ASI). Its targets and modifications are discussed, as are their
      use in clinical studies. Although some of the results are promising, the results
      still have to be confirmed in larger studies. Since there is sufficient evidence
      for immune reactivity in CRC, further research on immunotherapeutic strategies is
      justified and will be focused on the development of humanised antibodies, the
      search for other relevant T-cell epitopes and ways to induce a more effective T
      cell response.

PMID- 11978527
TI  - Treatment of liver metastases, an update on the possibilities and results.
AB  - Long-term results after liver resection for colorectal liver metastases show 5
      year survival rates between 35 and 40%. However, only a limited number of
      patients appear to be candidates for resection, far more patients prove to have
      unresectable disease. Present challenges in liver surgery for colorectal
      metastases are to improve patient selection, to increase the resectability rate
      and to improve survival by multimodality treatment approaches. The variables most
      consistently associated with a poor prognosis and tumour recurrence are tumour
      positive resection margins and the presence of extra-hepatic disease. Hence,
      patient selection and preoperative staging should concentrate on accurate imaging
      of the liver lesions and the detection of extrahepatic disease. For liver
      imaging, spiral computed tomography (CT) scan or magnetic resonance imaging
      (MRI), supplemented by intra-operative ultrasound, are currently regarded as the
      best methods for evaluating the anatomy and resectability of colorectal liver
      metastases. Extrahepatic disease should be investigated by spiral CT of the chest
      and abdomen and when possible by 2-fluouro-2-deoxy-D-glucose-positron emission
      tomography (FDG-PET). Resection remains the gold standard for the surgical
      treatment of colorectal liver metastases. In experienced centres, resection is a
      safe procedure and mortality rates are below 5%. The aim of resection should be
      to obtain tumour-negative resection margins. Edge cryosurgery should be
      considered in cases where very close resection margins are anticipated. The role
      of adjuvant chemotherapy after resection is still controversial, although two
      recent studies show a clear benefit. For the moment, local tumour ablative
      therapies such as cryotherapy and radiofrequency therapy should be considered as
      an adjunct to hepatic resection in those cases in which resection can not deal
      with all of the tumour lesions. In these cases, there seems a beneficial effect
      of a combined treatment consisting of resection and local tumour ablation. At
      this stage, there are no randomised data that local tumour ablation is as
      effective as resection. For a selected group of patients with unresectable liver
      metastases, there may be a chance to turn unresectable disease to resectable
      disease by aggressive neo-adjuvant chemotherapy or portal vein embolisation. For
      patients with unresectable disease, many different chemotherapy schedules may be
      used based on systemic drug administration. Regional chemotherapy and isolated
      liver perfusion should only be used within a study design.

PMID- 11978528
TI  - Membrane curvature: a case of endofeelin' ...

PMID- 11978529
TI  - The lipid origin of cellulose.

PMID- 11978530
TI  - TrkAing signals with clathrin.

PMID- 11978531
TI  - Loss of checkpoint proteins: an occupational hazard.

PMID- 11978532
TI  - Receptor tails and transcriptional regulation.

PMID- 11978535
TI  - Pinning down proline-directed phosphorylation signaling.
AB  - The reversible phosphorylation of proteins on serine or threonine residues
      preceding proline (Ser/Thr-Pro) is a major cellular signaling mechanism. Although
      it is proposed that phosphorylation regulates the function of proteins by
      inducing a conformational change, there are few clues about the actual
      conformational changes and their importance. Recent identification of the novel
      prolyl isomerase Pin1 that specifically isomerizes only the phosphorylated
      Ser/Thr-Pro bonds in certain proteins led us to propose a new signaling
      mechanism, whereby prolyl isomerization catalytically induces conformational
      changes in proteins following phosphorylation to regulate protein function.
      Emerging data indicate that such conformational changes have profound effects on
      catalytic activity, dephosphorylation, protein-protein interactions, subcellular
      location and/or turnover. Furthermore, this post-phosphorylation mechanism might
      play an important role in cell growth control and diseases such as cancer and
      Alzheimer's.

PMID- 11978536
TI  - MAP kinase cascade signaling and endocytic trafficking: a marriage of
      convenience?
AB  - A hallmark of many signaling pathways is the spatial separation of activation and
      deactivation of signaling proteins. Quantitative analysis demonstrates that the
      spatial separation of a membrane-bound kinase and a cytosolic phosphatase
      potentially results in precipitous gradients of target phosphoproteins.
      Hypothetically, such gradients in the mitogen-activated protein kinase (MAPK)
      cascade would result in a strong attenuation of the phosphorylation signal
      towards the nucleus. When effective signal transduction is hampered by slow
      protein diffusion and rapid dephosphorylation, phosphoprotein trafficking within
      endocytic vesicles might be an efficient way to propagate the signals. Additional
      mechanisms facilitating information transfer could involve the assembly of MAP
      kinases on a scaffolding protein and active transport of signaling complexes by
      molecular motors. The proposed mechanism explains recent observations that MAPK
      activation can be strongly suppressed by various inhibitors of endocytosis.

PMID- 11978538
TI  - Designer skin: lineage commitment in postnatal epidermis.
AB  - The epidermis is populated by stem cells that produce daughters that
      differentiate to form the interfollicular epidermis, hair follicles and sebaceous
      glands. Diffusible factors, cell-cell contact and extracellular matrix proteins
      are all important components of the microenvironment of individual stem cells and
      profoundly affect the differentiation pathways selected by their progeny. Here,
      we summarize what is known about stem-cell populations and lineage relationships
      within the epidermis. We also present evidence that postnatal epidermis can be
      reprogrammed, altering the number and location of cells that differentiate along
      specific epidermal lineages.

PMID- 11978537
TI  - Mitochondrial dynamics and division in budding yeast.
AB  - Mitochondria adopt a variety of different shapes in eukaryotic cells, ranging
      from multiple, small compartments to elaborate tubular networks. The
      establishment and maintenance of different mitochondrial morphologies depends, in
      part, on the equilibrium between opposing fission and fusion events. Recent
      studies in yeast, flies, worms and mammalian cells indicate that three high
      molecular-weight GTPases control mitochondrial membrane dynamics. One of these is
      a dynamin-related GTPase that acts on the outer mitochondrial membrane to
      regulate fission. Recently, genetic approaches in budding yeast have identified
      additional components of the fission machinery. These and other new findings
      suggest a common mechanism for membrane fission events that has been conserved
      and adapted during eukaryotic evolution.

PMID- 11978539
TI  - Protein kinase D: an intracellular traffic regulator on the move.
AB  - Recent research has identified protein kinase D (PKD, also called PKCmu) as a
      serine/threonine kinase with potentially important roles in growth factor
      signaling as well as in stress-induced signaling. Moreover, PKD has emerged as an
      important regulator of plasma membrane enzymes and receptors, in some cases
      mediating cross-talk between different signaling systems. The recent discovery of
      two additional kinases belonging to the PKD family and the plethora of proteins
      that interact with PKD point to a multifaceted regulation and a multifunctional
      role for these enzymes, with functions in processes as diverse as cell
      proliferation, apoptosis, immune cell regulation, tumor cell invasion and
      regulation of Golgi vesicle fission.

PMID- 11978540
TI  - Henry Bourne.

PMID- 11978543
TI  - The aggressive nature of the odontogenic keratocyst: is it a benign cystic
      neoplasm? Part 1. Clinical and early experimental evidence of aggressive
      behaviour.
AB  - In this, the first of three articles on the aggressive nature of the odontogenic
      keratocyst (OKC), there is a review of clinical and histological observations
      which indicated that this was an aggressive lesion with a predilection for
      recurrence unlike the majority of other jaw cysts. This led to the tentative
      suggestion that the OKC might be a benign neoplasm. Subsequently there were early
      laboratory investigations that compared proliferation rates of the OKC epithelium
      with other jaw cysts, comparative enzyme histochemistry to assess aspects of its
      metabolism and markers that would enable accurate presurgical diagnosis of this
      cyst. Comparative studies were also pursued on the walls of the OKC and other jaw
      cysts to identify factors that might influence the capacity of the OKC to resorb
      the bone surrounding it. The clinical and laboratory studies reviewed in this
      section provided cogent presumptive evidence of the distinctively aggressive
      nature of the OKC that led numbers of investigators to pursue immunocytochemical
      and genetic studies on this cyst. Parts 2 and 3 of this series review this work.

PMID- 11978544
TI  - Oral squamous cell carcinoma; from an hypothesis about a virus, to concern about
      possible sexual transmission.
AB  - Nearly two decades ago, we produced the first evidence for the presence of viral
      nucleic acids in oral squamous cell carcinoma (OSCC) tissues, hypothesising that
      there may be a viral involvement in at least some OSCC. Subsequently, human
      papillomaviruses (HPV) in particular have been implicated in OSCC. Antibody
      responses to HPV are seen and HPV-DNA detected in tumors by us and many others,
      the virus being mainly HPV-16, the genotype associated with ano-genital cancer.
      HPV are seen by in situ hybridisation only in tumour and premalignant tissue but
      not in surrounding normal mucosa suggesting HPV has a causal relationship. HPV
      may also be integrated in the host genome, further suggesting a causal role.
      Studies of patients with OSCC have suggested possible sexual transmission of HPV.
      Recent studies have indicated that HPV may be aetiologically important
      particularly in some types of oropharyngeal cancer, at least in tonsillar
      carcinogenesis, and may represent an alternative pathway in carcinogenesis to the
      established factors of tobacco and alcohol. We have come a very long way in the
      two decades since our first suggestion of a viral aetiopathogenesis was greeted
      with incredulity, and data from on-going studies by the International Agency for
      Research on Cancer, Johns Hopkins Oncology Center and others are eagerly awaited.

PMID- 11978545
TI  - Expression of cell cycle control proteins in normal epithelium, premalignant and
      malignant lesions of oral cavity.
AB  - In this study, we examined the expression of cyclins, cyclin dependent kinase
      (CDKs) and CDK inhibitors by immunohistochemical analysis in 20 normal mucosa, 42
      epithelial dysplasia (ED), and 117 oral squamous cell carcinoma. Neither Cyclin
      D1 nor CDK2 were detectable in normal tissue and ED. Their presence, however, was
      detectable in squamous cell carcinoma (SCCs) (Cyclin D1, 35.9%; CDK2, 66.7%).
      Cyclin E was detectable in 57.1% of severe ED and 62.8% of SCCs. For the CDK
      inhibitors, these proteins were detectable in all normal mucosa and most of the
      mild and moderate ED. For severe ED, expression of these proteins was not
      observed in some cases (p12(DOC-1), 14.3%; p16(INK4A), 28.6%; p27(KIP1), 7.1%).
      For SCCs, the expression of p12(DOC-1) was lost in 71.8%, p16(INK4A) in 69.2% and
      p27(KIP1) in 35.9%. These results suggest that elevated expression of cyclin D1,
      cyclin E, CDK2 and loss of p12(DOC-1), p16(INK4A) and p27(KIP1) may contribute to
      the multistep nature of oral carcinogenesis.

PMID- 11978546
TI  - Immunohistochemical expression of CA19-9 and CA125 in mucoepidermoid and adenoid
      cystic carcinomas of the salivary gland.
AB  - This study examined the immunohistochemical expression of carbohydrate antigens
      CA19-9 and CA125 and their relationship to various biological parameters in 27
      mucoepidermoid carcinomas (MEC) and 18 adenoid cystic carcinomas (ACC) arising
      from salivary glands. The series showed higher immunopositivity for CA125 (67%
      for MEC; 33% for ACC) than for CA19-9 (59% for MEC; 11% for ACC). CA19-9 epitope
      was mainly expressed in cystic (MEC) and cribriform/tubular (ACC) components of
      carcinoma tissues. Solid components in MEC occasionally showed positive staining
      for CA19-9. CA125 was evenly expressed in both ACC and MEC tissues regardless of
      their different histological components. The positive expression of CA19-9 and
      CA125 in the carcinoma tissues did not influence the clinical course of patients
      with MEC and ACC. A significant relationship was only demonstrated between the
      immunohistochemical expression of CA125 and the low proliferative activity (LI)
      evaluated by Ki-67 immunohistochemistry. However, no significant relationship was
      found between LI and the patients' clinical course. These results suggest that
      the immunostaining for CA19-9 and CA125 provide no reliable data to predict the
      clinical course of patients with MEC and ACC of the salivary glands.

PMID- 11978547
TI  - Hypoxic induction of HIF-1alpha and VEGF expression in head and neck squamous
      cell carcinoma lines is mediated by stress activated protein kinases.
AB  - Solid tumors must establish a blood supply in order to proliferate and grow.
      Cancer cells secrete soluble factors which can induce proliferation and migration
      of capillary endothelial cells. Among the most potent of the angiogenic factors
      is vascular endothelial growth factor (VEGF). Increased VEGF expression by
      malignant tumors has been associated with high vascularity, increased cancer cell
      growth, and lymph node metastasis. Reduced oxygen tension has been shown to
      increase VEGF production by induction of the transcription factor hypoxia
      inducible factor 1 alpha (HIF-1alpha). The mechanisms by which hypoxic tumor
      environments induce HIF-1alpha and VEGF expression are largely unknown. Jun N
      terminal kinase (JNK1) and p38 kinase are activated by a variety of stress
      stimuli. To determine if hypoxic activation of these stress activated protein
      kinases regulated HIF-1alpha and VEGF expression, we assayed JNK1 and p38
      activity in squamous cell carcinoma (SCC) lines grown under normoxic or hypoxic
      conditions. Hypoxia rapidly induced both JNK1 and p38 activity in these cells.
      This activation correlated with induction of HIF-1alpha expression and DNA
      binding activity which was blocked by the p38 inhibitor SB203580. Hypoxia also
      increased VEGF production by SCC lines, which was inhibited by treatment with
      SB203580. Overexpression of JNK1 or p38 was sufficient to induce HIF-1alpha and
      VEGF expression. These results indicate that induction of SAPKs by hypoxia
      regulates HIF-1alpha and VEGF expression in head and neck carcinoma cell lines.

PMID- 11978548
TI  - Prevention of the areca nut extract-induced unscheduled DNA synthesis of gingival
      keratinocytes by vitamin C and thiol compounds.
AB  - There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is
      the major risk factor of oral cancer in India, Taiwan, South Africa and numerous
      other countries. Areca nut (AN) extract, the main component of BQ, exerts
      cytotoxicity and genotoxicity to several types of cells. In the present study, AN
      extract induced the unscheduled DNA synthesis (UDS) of gingival keratinocytes
      (GK). Vitamin C, at concentration of 50 and 200 microg/ml prevented the AN
      induced UDS by 41 and 56%, respectively. Glutathione (GSH, 1-3 mM) and N-acetyl-L
      cysteine (NAC, 1-3 mM) also protected the AN-induced UDS by 89-100 and 76-90%.
      These preventive effects were not due to cytotoxicity as analyzed by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Deferoxamine
      (20 and 30 mM), an iron chelator and a free radical scavenger, also prevented AN
      extract induced UDS of GK by 30-55%. On the contrary, banthocuproine (50-200
      microM, a copper chelator) and 1,10-phenanthroline (50, 100 microM, a lipid
      permeable iron chelator), lacked preventive effects. Specific reactive oxygen
      species scavengers such as dimethyl-sulfoxide (2%), mannitol (10-20 mM),
      dimethylthiourea (10-20 mM), pyruvate (10 mM), catalase (200 and 400 U/ml), and
      superoxide dismutase (50 and 200 U/ml) also lacked these preventive effects.
      Moreover, higher concentrations of H(2)O(2) (0.5-1 mM) inhibited the basal levels
      of UDS by 19-37%. Interestingly, NAC, GSH, Vitamin C and deferoxamine cannot
      prevent the AN-induced morphological changes of GK at similar concentrations.
      These results reveal that AN extract-induced UDS of GK is associated with free
      radical reactions. Possibly different ingredients of AN is responsible for
      genotoxicity and cytotoxicity. Vitamin C, GSH and NAC may be potentially used in
      the future for chemoprevention of BQ chewing related oral mucosal lesions.

PMID- 11978549
TI  - Chromosomal changes in betel-associated oral squamous cell carcinomas and their
      relationship to clinical parameters.
AB  - To investigate the chromosomal imbalances that occur in oral carcinoma associated
      primarily with betel use and their clinical implications, we performed
      chromosomal analysis using comparative genomic hybridization on 47 patients with
      this disease. The most common gains of chromosome arms were 8q, 9q and 11q, and
      the most frequent losses were of chromosomal arms 3p and 4q. The clinical
      parameters significantly associated with the numbers of chromosomal imbalances
      per tumor were the age of the patients and nodal metastasis. The preliminary
      findings of a lower incidence of loss of 4q and gain of 8q in betel-associated
      tumors compared to non-betel-associated tumors might provide insight into the
      carcinogenic effect of betel. Deletion of 3p and the gain of 11q alterations were
      more prevalent in carcinomas with lymph node metastasis than in node-negative
      tumors, indicating possible loci for metastasis suppressor or metastasis
      enhancing genes, respectively. Losses of 3p and 4q and gain of 9q were associated
      with poor outcome for the patients. These data demonstrated that the frequent
      aberrations in 4q and 9q sites can be used as novel prognostic predictors.

PMID- 11978550
TI  - Apoptosis, proliferation and p12(doc-1) profiles in normal, dysplastic and
      malignant squamous epithelium of the Syrian hamster cheek pouch model.
AB  - Disruption of the homeostatic balance between proliferation and apoptosis is
      widely believed to contribute to human oral carcinogenesis. Using the Syrian
      hamster oral cancer model, we examined normal, hyperplastic, dysplastic and
      malignant oral epithelium for the fraction of apoptotic, proliferating and
      p12(doc-1) expressing keratinocytes using the TUNEL assay, as well as PCNA and
      p12(doc-1) immunostaining, respectively. The percentage of TUNEL positive cells
      progressively increased from normal to dysplastic epithelium (P<0.0019), but
      returned to normal keratinocyte levels in the malignant epithelium (P<0.20).
      However, PCNA positive cells increased progressively through hamster oral
      malignant progression (P<0.0012). The overall ratio of apoptotic to proliferating
      keratinocytes remains similar until the transition between dysplastic and
      malignant epithelium, where the ratio is markedly reduced (P<0.05). p12(doc-1)
      labeling demonstrated a similar expression pattern (P<0.008). This study
      demonstrates that apoptosis, proliferation and the expression of p12(doc-1)
      reflects alterations reported during human oral carcinogenesis and supports the
      use of the Syrian hamster model for the further examination of these pathways.

PMID- 11978551
TI  - Acetaldehyde activates Jun/AP-1 expression and DNA binding activity in human oral
      keratinocytes.
AB  - Oral cancer is a significant health problem, particularly among individuals that
      ingest alcohol in combination with the use of tobacco products. The enhanced
      development of tobacco-initiated oral cancers by ethanol suggests that ethanol or
      one of its metabolites may act as a type of tumor promoter. Nevertheless, the
      mechanisms underlying the ability of ethanol to enhance oral carcinogenesis
      remain unclear. We hypothesize that acetaldehyde, the first metabolite of
      ethanol, may activate the expression and/or activity of Jun/AP-1 in oral
      keratinocytes analogous to the phorbol ester TPA and other tumor promoters in
      epidermal keratinocytes. To test this hypothesis, we treated HPV immortalized,
      non-tumorigenic human oral keratinocytes with acetaldehyde at various
      concentrations and for various times and measured several parameters of Jun/AP
      1expression and function. Our results indicated that c-Jun mRNA and protein
      levels increased in the acetaldehyde treated cells compared to untreated control
      cells. Moreover, Jun/AP-1 DNA binding activity was rapidly activated by
      acetaldehyde in a dose-dependent fashion. The increases in Jun protein and AP-1
      DNA binding activity were accompanied by increased transactivation of an AP-1
      responsive reporter construct as well as increased transcript levels of a
      candidate AP-1 responsive gene, stromelysin 3. The levels of acetaldehyde
      employed were minimally toxic to the cells as determined by MTT assays. Thus,
      acetaldehyde was found to activate the expression and activity of an oncogenic
      transcription factor in HPV-initiated cells. Taken together, these results
      suggest that acetaldehyde may participate, at least in part, in the promotion
      stage of oral carcinogenesis.

PMID- 11978552
TI  - The influence of clinical factors on human stimulated parotid flow rate in cancer
      and other patients.
AB  - Reduced salivary secretion can produce a wide variety of complaints, having a
      negative impact on the daily life of a patient. Multiple causes of salivary
      hypofunction are described, however, there are no consistent data about the
      influence of clinical parameters on parotid gland function. We studied a group of
      patients with head and neck malignancies before treatment with radiotherapy. We
      used Lashley cups to collect stimulated parotid saliva simultaneously from both
      parotid glands. Sizes of the parotid gland, gender, age, tobacco and alcohol
      consumption, and tumour characteristics were related to the function of the
      parotid gland. A considerable variability in parotid output was found with a
      range of 0.03-1.66 ml/min (mean 0.34 ml/min). None of the variables were
      correlated with parotid flow. These results are important, especially when
      evaluating effects of radiation on parotid gland function.

PMID- 11978553
TI  - P53 tumor suppressor gene mutations in laryngeal cancer and in recurrent disease
      following radiation therapy.
AB  - In this study we performed p53 sequencing based mutation analysis in laryngeal
      cancers and matched recurrent disease following irradiation. The question is if
      irradiation affects the DNA and introduces or deletes mutations so that p53
      cannot be used as a clonal marker anymore. P53 mutations were identified in fresh
      frozen laryngectomy specimens with either primary laryngeal cancers, treated by
      surgery and irradiation post-operative with local failure during follow-up, or
      with recurrent laryngeal cancers following primary irradiation. In 21 tumors the
      p53 status was analyzed by direct sequencing full-length mRNA through RT-PCR. DNA
      sequencing analysis of exons 2 through 11 was performed when RNA isolation could
      not be performed. The marker mutation identified in this way was detected by DNA
      sequencing of the corresponding exon in formalin-fixed deparaffinized tumor
      biopsy samples in respectively matched recurrent disease following surgery and
      irradiation or primary tumor before irradiation. DNA sequencing analysis of the
      corresponding exon of peripheral blood leukocytes excluded the presence of
      germline mutations or polymorphisms. In 16 out of 21 tumors (71%), a mutation was
      identified. Fifteen of these marker mutations were detected in the matched tumor
      biopsy sample (94%). The only case lacking the marker mutation probably was a
      second primary tumor. We conclude that we find no direct evidence for induction
      or loss of p53 mutations following irradiation. Consequently, p53 may be used as
      a diagnostic tool when histological examination fails, for example in
      discriminating between the presence of a second primary tumor in the same area
      versus recurrent disease.

PMID- 11978554
TI  - Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the oral cavity:
      clinicopathological and prognostic significance.
AB  - The prognostic and clinicopathologic significance of cyclin D1 and Ki-67
      expressions was studied in oral squamous cell carcinomas. We performed an
      immunohistochemical study to determine the level of expression of cyclin D1 and
      Ki-67 labelling index in tumor specimens obtained from 35 patients, of whom 14
      died as a result of recurrent disease, and 20 were free of recurrence at the end
      of the follow-up period. Overexpression of cyclin D1 was significantly associated
      with regional lymph node metastases (P=0.00005) and advanced tumor stage
      (P=0.0007). The relative risk for nodal metastases in the cases that
      overexpressed cyclin D1 was 2.6. The Ki-67 labelling index was significantly
      (P=0.001) higher in tumors with poor histologic grade of differentiation. Our
      results showed that cyclin D1 is a useful prognostic factor, and suggested it
      could be a marker to help determine the appropriate treatment for patients with
      oral squamous cell carcinoma. Cyclin D1 and Ki-67 overexpression were positively
      correlated.

PMID- 11978555
TI  - The role of supraomohyoid neck dissection in patients of oral cavity carcinoma.
AB  - The aim of this study was to evaluate the role of supraomohyoid neck dissection
      (SOHND) in oral carcinoma patients with clinically negative neck nodes. From July
      1993 to June 1998, 140 patients with oral carcinomas and clinically negative
      lymph nodes in the neck underwent elective SOHND in Chang Gung Memorial Hospital,
      Taiwan. Thirty-seven patients had postoperative radiotherapy.Thirty-four (24.3%)
      patients had occult cervical metastases. The overall regional control rates were
      93.4% vs. 85.3% for pathologically negative vs positive nodes, respectively, with
      or without adjuvant radiotherapy. Adjuvant radiotherapy significantly improved
      ipsilateral regional control (P=0.012) in patients with occult cervical
      metastases but not in patients with negative neck disease. (P=1.0) SOHND is both
      a diagnostic and therapeutic procedure in patients with negative neck disease.
      Its therapeutic role in patients with positive neck disease remains
      controversial. Postoperative radiotherapy significantly improve ipsilateral neck
      control in patients with occult cervical metastasis.

PMID- 11978556
TI  - Carotid body tumour.
AB  - A case of carotid body tumour (paraganglioma) which is both unusual and highly
      vascular, arising from the carotid body is reported. The patient was a 68-year
      old female with a right submandibular swelling. The initial pathological
      diagnosis was obtained from the incisional biopsy. Carotid angiography revealed
      the feeding vessels arising only from the external carotid artery. The tumour was
      completely removed and no evidence of recurrence could be found 2-years
      postoperatively.

PMID- 11978557
TI  - Peripheral ameloblastoma is not a hamartoma but rather more of a neoplasm.

PMID- 11978558
TI  - Benign fibrous histiocytoma: an additional case richly endowed with factor
      XIIIa(+) cells.

PMID- 11978559
TI  - Current therapeutic strategies for hyperhidrosis: a review.
AB  - Overproduction of sweat by the exocrine sweat glands is called hyperhidrosis. It
      is differentiated into two forms - a localised (e.g. axillary, palmar and plantar
      hyperhidrosis) and a generalised form that affects the entire skin. Patients with
      increased sweat production often suffer from enormous psychosocial stress because
      they are restricted in both their private and professional lives. If the
      hyperhidrosis is not caused by a primary disease (e.g. hyperthyroidism or
      phaeochromocytoma) that can be treated, with elimination of the sweating problem,
      then only symptomatic treatment is possible. For axillary hyperhidrosis, local
      application of aluminium chloride seems to be the method of choice; an
      alternative is botulinum toxin whose efficacy for 3 to 9 months is an advantage.
      Surgical options should not be considered until conservative methods have failed.
      Curettage with a scraper and liposuction are reliable and safe treatments for
      axillary hyperhidrosis. The method of choice in treating palmoplantar
      hyperhidrosis is tap water iontophoresis. Adding anticholinergic substances to
      the water produces a more rapid therapeutic success that also lasts longer.
      Botulinum toxin can be an effective and promising alternative. Surgical
      treatment, i.e. sympathectomy, does bring about a long-term resolution of the
      problem, but should only be considered in well-justified cases because of the
      highly invasive character of the procedure. The use of systemic anticholinergic
      medication for patients with localised or generalised tendency to sweat can be
      tried, but is often limited because of the profile of adverse effects. It can be
      stated that in spite of the interesting and promising new alternatives,
      especially using botulinum toxin, the tried-and-true procedures such as tap water
      iontophoresis and aluminium chloride salts still have a firm place in the
      treatment of hyperhidrosis.

PMID- 11978560
TI  - Innate immunity.
AB  - For more than half a century immunological research has been almost exclusively
      orientated towards the acquired immune response and the mechanisms of immune
      tolerance. Major discoveries have enabled us to better understand the functioning
      of the specific immune system: the structure of antibody molecules, the genetic
      mechanisms leading to the molecular diversity of B (BCR) and T (TCR) lymphocyte
      antigen receptors, the biological function of major histocompatibility complex
      (MHC) molecules in the presentation of peptides to alpha/beta receptor bearing T
      lymphocytes, the processes of positive and negative selection of lymphocytes
      during the course of their differentiation. The major role of specific or
      acquired immunity has been shown by the rapidly lethal character of severe
      combined immune deficiency diseases and various alterations in the mechanisms of
      tolerance have been proposed to explain the chronic inflammatory illnesses which
      are considered to be auto-immune. Natural or innate immunity has been known since
      the first description of an inflammatory reaction attributed to Cornelius Celsus.
      It entered into the scientific era at the end of the 19th century with the
      discovery of phagocytes by Metchnikoff and of the properties of the complement
      system by Bordet [1] but due to the vastness of the field and its lack of clear
      definition, it failed to excite the interest of researchers. The discovery of
      cytokines and progress in knowledge of the mechanisms of the inflammatory
      reaction have certainly helped to banish preconceived ideas about natural
      immunity, which was wrongly labelled as non-specific. This has led to the
      proposition of a wider role for immune functions beyond the level of the cell or
      the organism [2] and to a better understanding of the importance of the immediate
      defence mechanisms and their role in the later orientation of the acquired
      response.

PMID- 11978561
TI  - Aplasia cutis congenita in two siblings.
AB  - We report on two siblings with aplasia cutis congenita (ACC). This rare
      congenital malformation is characterized by a local defect of epidermis, dermis,
      and subcutaneous tissues occurring predominantly on the vertex of the scalp.
      Patient A (a boy) was born with a parietooccipital 4 x 4 cm scalp defect, that
      healed under conservative treatment with scar formation within three months. At
      the age of three years we started with serial excisions of the affected area. In
      patient B (a girl) two 1.5 x 1.5 cm midline scalp defects were noted at birth.
      After primary conservative treatment we performed an excision at the age of three
      years. Both children were born at term following normal pregnancy and delivery.
      Neither physical nor psychomotor retardation nor any other associated abnormality
      was found in these cases. Two younger brothers were born without any skin defects
      or other anomalies. There is no unifying theory on the pathogenesis of ACC.
      Traumatic, vascular, teratogenic, and genetic factors are discussed as initial
      steps in etiopathogenesis. In this family the occurrence of ACC in two siblings
      of either sex, with unaffected parents, may suggest an autosomal recessive mode
      of transmission. However autosomal dominant inheritance with germline mosaicism
      in one parent can not be excluded.

PMID- 11978562
TI  - Lysine acetylsalicylate decreases proliferation and extracellular matrix gene
      expression rate in keloid fibroblasts in vitro.
AB  - BACKGROUND: In genetically predisposed individuals keloids are formed as benign
      collagenous tumors. OBJECTIVE: The purpose of this study was to investigate
      whether the proliferation and matrix gene expression of keloid fibroblasts is
      differently influenced by the anti-inflammatory active drug lysine
      acetylsalicylate (LAS) when compared to normal skin fibroblasts in vitro.
      METHODS: Normal skin and keloid fibroblasts derived from human donors were
      compared. RESULTS: Excessive scarring and the formation of keloids are (at least
      in part) due to an overproduction of collagen types I and III. The results show a
      significant dose-dependent anti-proliferative effect of lysine acetylsalicylate.
      At the level of gene expression we observed a pronounced inhibitory effect of LAS
      on procollagen I and III mRNA synthesis, whereas matrix metalloproteinase 1 and
      tissue inhibitor of metalloproteinases 1 were not altered. CONCLUSIONS: Further
      clinical studies are planned to evaluate these effects of a high-dose treatment
      of keloids with LAS.

PMID- 11978563
TI  - HLA class II alleles in patients with alopecia areata.
AB  - Our purpose was to determine which HLA class II alleles are associated with
      Turkish alopecia areata patients. Also we investigated whether there was a
      relationship between the age of onset and severity of disease and HLA alleles or
      not. Sixty-five patients with alopecia areata were included in this study, and 50
      healthy transplant donors were used as a control group. The total group of
      alopecia areata patients as well as various subgroups according to scalp hair
      loss were compared to the control group. HLA DNA typing was performed by
      polymerase chain reaction/sequence specific primer method. The frequency of
      DQB1*03 allele was 86.1% in all patients compared to 62.0% in controls (P =
      0.005). While the frequency of DQB1*03 was significantly increased, the frequency
      of DRB1*03 was decreased in the all patients group (4.6% versus 22.0%, P = 0.01).
      In the group of scalp hair loss less than 25%; the frequency of DRB1*03 was
      decreased (3.2%, P = 0.02). The group of patients with 25-75% scalp hair loss was
      compared to control group; the frequencies of DRB1*04 (66.7% versus 28.0%, P =
      0.02) was increased. When the alopecia totalis, alopecia universalis or alopecia
      totalis/alopecia universalis group was compared to control group; DQB1*03 was
      associated with an increased frequency in this group versus control group (90.9%,
      P = 0.03). There were no significant differences for the other DQ alleles and the
      DR alleles tested in the patients and in the controls. When patients with early
      onset were compared to patients with late onset; no significant allele
      differences were found. Our findings suggested that DQB1*03 allele is a marker
      for general susceptibility to alopecia areata and may also serve as special
      genetic marker for susceptibility for the severe form of alopecia areata in our
      population. However, this association is not related to age at onset of the
      disease.

PMID- 11978564
TI  - The metalloprotease-directed shedding of BP 180 (collagen XVII) from human
      keratinocytes in culture is unaffected by ceramide and cell-matrix interaction.
AB  - The constitutive shedding of BP180 (collagen XVII) from human keratinocytes in
      culture was totally prevented by batimastat (5 microM), a wide spectrum matrix
      metalloprotease (MMP) inhibitor. However, keratinocytes did not express active
      MMP and generation of active Gelatinase A (MMP-2) and Gelatinase B (MMP-9) at the
      cell plasma membrane by increasing the ceramide content of keratinocytes did not
      influence BP180 processing to a 120 kDa species. A disintegrin and
      metalloprotease (ADAM) is probably involved in such a shedding event since
      release of 120 kDa polypeptide was inhibited by Decanoyl-Arg-Val-Lys-Arg CH2Cl
      (30 microM), a specific furin convertase inhibitor; culturing cells on to several
      matrix substrata i.e. type I collagen, type IV collagen, laminin-1 or laminin-5
      had no effect on BP180 processing. Overall our data indicated that the
      metalloprotease-mediated shedding of BP180 from keratinocytes in culture is
      insensitive either to agents which activate MAP kinase pathway (ceramide) or to
      cell-matrix interactions.

PMID- 11978565
TI  - Skin ageing: clinical and histopathologic study of permanent and reducible
      wrinkles.
AB  - Wrinkles are modifications of the skin associated with cutaneous ageing and
      develop preferentially on sun-exposed skin. The aim of the study was to analyse
      the clinicopathological features of wrinkles, among the different types of skin
      relief modifications. Despite its importance in dermato-cosmetology and skin
      ageing, few studies have been specifically devoted to wrinkles. In the present
      study, we analyzed the histological features of the pre-auricular wrinkle
      compared to retro-auricular skin, obtained from sixteen patients undergoing
      facial surgery; skin samples were immediately processed for routine histology and
      histochemical staining. Four types of skin depressions could be defined according
      to their depth: folds, permanent wrinkles, reducible wrinkles and skin micro
      relief. Two different types of pre-auricular wrinkles were observed: (i)
      permanent wrinkles which were conserved after sampling and, (ii) reducible
      wrinkles which required in vivo staining to be visible at histology. Histological
      analysis of the epidermis and dermis of the skin forming the pre-auricular
      wrinkle revealed a normal skin morphology, identical to that of the skin
      immediately adjacent to the wrinkle. This was particularly striking for the
      reducible wrinkles which could not be individualized in the absence of in vivo
      staining. Both types of wrinkles comprised skin modifications observed in sun
      exposed skin, however, in the upper dermis, permanent wrinkles showed a more
      pronounced accumulation of basophilic fibers, i.e. actinic elastosis, than
      reducible wrinkles did. These data suggest that the development of wrinkles could
      be secondary to actinic elastosis and to the disappearance of microfibrils and
      collagen fibers at the dermal-epidermal junction.

PMID- 11978566
TI  - Rash orientation in pityriasis rosea: a qualitative study.
AB  - Rash orientation in pityriasis rosea (PR) has been described as Christmas-tree
      pattern, inverted Christmas-tree pattern, fir tree pattern, parallel to the ribs
      or along skin cleavage lines. We retrieved clinical photographs of 11 patients
      diagnosed as having PR over a two-year period for qualitative study of rash
      orientation. We found that Langer's cleavage lines are the most appropriate
      description. All three components of these lines on the trunk, i.e. V-shaped
      pattern on upper chest and upper back, circumferential pattern around the
      shoulders and hips, and transverse pattern on the lower anterior trunk and lower
      back, are demonstrated by most patients. We believe with the present state of
      knowledge, the mechanism for PR following Langer's lines is best considered
      unknown. We advocate abandoning other descriptions which might cause confusion to
      students and trainee physicians.

PMID- 11978567
TI  - Heart structure and function in systemic sclerosis.
AB  - INTRODUCTION: Systemic sclerosis (SSc) is a multisystem disorder characterised by
      connective tissue fibrosing with vascular abnormalities and autoimmune changes.
      Heart involvement is one of the main factors shortening the survival of SSc
      patients. AIM OF THE STUDY: (1) To assess structural and pathophysiological
      changes of the heart in SSc patients in standard echocardiographic examination.
      (2) To evaluate regional systolic and diastolic left ventricle disturbances in
      SSc patients by means of Tissue Doppler Imaging (TDI). MATERIAL AND METHODS: In
      19 SSc women aged 22-72 years and 16 control healthy women aged 19-57 years M
      Mode, 2D, Continuous Doppler, Colour Doppler and Tissue Doppler examinations were
      performed. Tissue Doppler myocardial velocities in systole and early diastole
      were evaluated in 14 myocardial segments in parasternal and apical views.
      RESULTS: No significant differences between both groups in left ventricle (LV)
      ejection fraction, LV end-diastolic and end-systolic diameter, LV wall thickness,
      valvular structure was observed. Mitral E/A ratio was significantly decreased in
      SSc women (p < 0.001), and pulmonary systolic pressure was significantly
      increased in this group (p < 0.001). In TDI examination no significant difference
      between the groups in systolic myocardial velocity was found. In SSc women early
      diastolic velocities were significantly lower than in controls (p < 0.00001). The
      detailed assessment of diastolic function in SSc group showed severe diastolic
      dysfunction of longitudinal myocardial fibers with normal function of circumflex
      myocardial fibers. CONCLUSIONS: In SSc patients significant left ventricle
      diastolic dysfunction was found. Diastolic dysfunction was observed only in
      longitudinal myocardial fibres and was not found in circumflex myocardial fibres.
      Thus, myocardial fibrosing and ischemia in SSc patients seem to be concentrated
      in the subendocardial region built by longitudinal muscle layer. Left ventricle
      diameter, walls thickness and systolic function in SSc patients are preserved.

PMID- 11978568
TI  - Sjogren-Larsson syndrome: biochemical defects and follow up in three cases.
AB  - Sjogren-Larsson syndrome is a rare disorder that consists of congenital
      ichthyosis and neurological symptoms due to an enzymatic defect of fatty aldehyde
      dehydrogenase in the fatty alcohol cycle. We report three cases of Sjogren
      Larsson syndrome in which the primary biochemical defect was established in two
      patients (patient 2: 175 pmol/min/mg; patient 3: 103 pmol/min/mg protein
      enzimatic activity in fibroblasts in skin, while normal controls were 8,860 +/-
      1,624, n: 22 ). A dietary program was proposed: reduced total fatty intake at 30%
      of total calories, n-3 and n-6 acids (canola oil) as well as unsaturated fatty
      acids (Milupan milk). Topical keratolytic agents were used too. Good clinical
      course was observed in one of the patients in whom dietary intervention was
      started in early infancy. In the other two patients, who started the therapy
      later (five and three years old), cutaneous symptoms were improved after
      treatment.

PMID- 11978570
TI  - Acute leucocytoclastic vasculitis and aquagenic pruritus long preceding
      polycythemia rubra vera.
AB  - We describe the unusual case of a 67-year-old woman with aquagenic pruritus,
      immediately following acute cutaneous leucocytoclastic vasculitis and preceding
      the development of polycythemia rubra vera by 3 years.

PMID- 11978569
TI  - Launois-Bensaude syndrome and Bureau-Barriere syndrome in a psoriatic patient:
      successful treatment with carbamazepine.
AB  - Authors report a 41-year-old male patient with multiple symmetric lipomatosis,
      who also had psoriasis. In addition he suffered from peripheral neuropathy, acro
      osteolysis and malum perforans pedis fulfilling the criteria of Bureau-Barriere
      syndrome. Considering the severe peripheral neuropathy and the preliminary report
      on the efficacy of carbamazepine in psoriasis, a carbamazepine monotherapy was
      initiated for both indications. The psoriatic skin symptoms cleared within 6
      weeks. The patient has continued this medication for 8 months without side
      effects. During that time his skin remained symptom free and the neuropathy has
      improved.

PMID- 11978571
TI  - Tinea barbae due to Trichophyton verrucosum.
AB  - A 25 year-old male, a dairy farmer, had noticed an annular scaly erythema on the
      left cheek since 3 weeks, and visited a dermatological clinic for the eruption.
      Diagnosis of tinea faciei was made and he was treated with oral anti-histamine
      medicine and by topical application of anti-fungal ointment. However, the
      eruption worsened and enlarged so that he visited the department of dermatology
      of Kumiai Hospital on October 19, 1997. He was in good general health. Physical
      examination disclosed papules and pustules with swelling and erythema on the chin
      and cheeks. The results of routine laboratory investigations were within normal
      limits except for white blood cell (9,800/mm(3)) and C reactive protein (2+). A
      small white-yellowish colony was grown on brain heart infusion agar culture of
      the biopsied specimen of the lower jaw. Histopathological features showed
      epidermal hyperplasia with elongation of rate ridges and granulomatous changes
      around hair follicles in the dermis with many mononuclear cells and giant cells,
      where many positive spores and fine filamentous structures with PAS and Grocott
      stains were seen. Based on clinical, histopathological and mycological findings,
      a diagnosis of Trichophyton verrucosum was made. The patient was treated with
      oral itraconazole (100 mg/day) for two months. There was a good clinical response
      and no recurrence during three years and six months.

PMID- 11978572
TI  - Multiple Bowen's disease of the fingers.
AB  - We describe herein a case of multiple Bowen's disease that developed on the left
      hand fingers of an 80-year-old male patient who had practiced as a gynecologist.
      PCR-based analysis indicated that the lesion contained human papillomavirus (HPV)
      type 18 DNA. Topical application of bleomycin and liquid nitrogen cryotherapy
      were effective in treating this case. After treatment, histopathologically no
      atypical cells were seen throughout the epidermis.

PMID- 11978574
TI  - Autoimmune polyglandular syndrome (APS) type 1 and candida onychomycosis.
AB  - A 21-year-old female presented at age 2 years with a chronic mucocutaneous
      candidiasis and at age 3 alopecia totalis. Later, chronic hypoparathyroidism and
      autoimmune adrenal insufficiency appeared. In addition, malabsorption syndrome
      and signs of pernicious anaemia occurred. The onychomycosis totally improved
      under systemic treatment with fluconazole (Diflucan), endocrine and organ failure
      with replacement therapy. The autoimmune polyglandular syndrome (APS 1) is a rare
      autosomal recessive inherited disease. Chronic mucocutaneous candidiasis (CMC)
      generally presents very early in life and is the most frequent of the three main
      diseases of APS type 1 (chronic hypoparathyroidism, autoimmune Addison's
      disease). It can be considered as a precocious marker of APS type 1.
      Consequently, all patients affected by isolated CMC, especially children, should
      be evaluated and carefully followed up by immunological, biochemical, and
      clinical tests to recognize signs and symptoms of imminent or ongoing endocrine
      glandular failure.

PMID- 11978573
TI  - Cutaneous necrosis revealing the coexistence of an antiphospholipid syndrome with
      acquired protein S deficiency, factor V Leiden and hyperhomocysteinemia.
AB  - We report an exceptional case of cutaneous necrosis due to the coexistence of 4
      thrombophilic factors, inherited and acquired. We would like to draw attention to
      these unrecognized associations. CASE REPORT: A 72-year-old woman was admitted
      with a 5 month history of necrotic nonhealing, painful ulcer of both legs and
      recently a purple toe. She had a history of 3 deep venous thromboses of the leg
      complicated by pulmonary embolism. A skin biopsy of the ulcer and purple toe
      showed only thrombosis in the dermal vessel. Laboratory findings showed a
      circulating lupus anticoagulant, positive anticardiolipin antibodies, antinuclear
      antibodies (1/320 dilution) and an anti Sm. Moreover, activated protein C
      resistance associated with factor V Leiden mutation and hyperhomocysteinemia was
      found; protein S was transiently low. With iloprost, oral anticoagulant, vitamin
      B12 and folic acid, the evolution was good, with healing of ulcer. COMMENTS:
      cutaneous necrosis can reveal hypercoagulable states, sometimes complex. We find
      4 thrombophilic factors in our case, i.e. antiphospholipid antibodies, factor V
      Leiden, protein S deficiency and hyperhomocysteinemia. This is exceptional but
      highlights the role of several constitutional and acquired thrombophilic factors
      in the genesis of thrombosis. Extended protein C pathway disturbances could
      explain the mechanism that leads to cutaneous necrosis, in this patient, with an
      antiphospholipid syndrome. This case shows that it is necessary in some
      circumstances to make a complete hemostatic laboratory search to detect several
      thrombophilic factors. If they are present they can justify an oral anticoagulant
      treatment and a familial screening.

PMID- 11978575
TI  - Sustained remission of Sezary syndrome.
AB  - Sezary syndrome, an aggressive form of cutaneous T-cell lymphoma, is a
      devastating, highly symptomatic form of non-Hodgkin lymphoma. Malignant clones of
      mature helper CD4 T cells containing large, convoluted nuclei known as Sezary
      cells circulate in the blood and infiltrate the skin. Clinical features include
      exfoliative erythroderma, generalized lymphadenopathy, alopecia, onychodystrophy,
      palmoplantar hyperkeratosis, and ectropion. Patients often have severe pruritus,
      burning sensations, pain, bleeding from excoriations, and disfigurement.
      Extracorporeal photopheresis, an immunomodulatory therapy, has become a primary
      therapy for these patients. This pheresis-based therapy uses psoralen and
      ultraviolet A radiation-mediated photochemotherapy to induce immune responses.
      The effects of extracorporeal photopheresis vary considerably. We report
      sustained remission (2 years) in a patient with Sezary syndrome. Previously he
      had received extracorporeal photopheresis and interferon alfa-2b injections. He
      is the only one of 55 patients with Sezary syndrome treated at Mayo Clinic
      (Rochester, Minnesota, USA) to achieve sustained remission on extracorporeal
      photopheresis alone.

PMID- 11978577
TI  - Guess what! Multiple pilomatricomas and Steiner disease.
AB  - An 18-year-old male adolescent was referred to our department for the presence of
      multiple skin nodules since the age of 9 years. At the age of 22 months the
      patient was diagnosed as having myotonic dystrophy (Steinert's disease). So far,
      nine lesions like these have been excised and histologically analysed, two
      located on the left arm, one on the neck and one on the scalp. A skin examination
      revealed three nodular lesions, two localised on the scalp (Fig. 1) and one on
      the trunk (Fig. 2); the lesions ranged from 0.5 to 3.5 cm, and were hard on
      palpation and asymptomatic, with elevated, smooth and teleangiectatic borders and
      a central invagination filled with whitish, firm, granular material. The lesions
      were all excised. The histological examination of all the biopsy specimens
      revealed basophilic cells at the periphery, and islets of shadow cells with an
      unstained central area at the site of lost nucleus (Fig. 3). The shadow cells
      were surrounded by a granulomatous infiltration composed mainly of giant cells.

PMID- 11978576
TI  - Guess what! Pseudomonas aeruginosa sepsis.
AB  - A 62-year-old woman affected by end-stage renal disease secondary to
      Waldenstrom's disease was admitted to place a central venous catheter for
      hemodialysis purposes. During the admission, she gradually developed a number of
      necrotic ulcerative and fluctuant nodular skin lesions on the submammary
      flexures, groins and limbs accompanied by high fever and chills. Yellow-green
      purulent material could be drained from the site of introduction of the jugular
      catheter. Skin biopsies were taken from the edge of an inguinal necrotic
      ulcerative lesion and from a fluctuant nodular lesion of the thigh, where pus was
      drained and cultured.

PMID- 11978579
TI  - Scleroderma and malignancy. Mechanisms of interrelationship.
AB  - The association of scleroderma and malignancy has been a source of controversy
      during recent years. Several mechanisms of interrelationship have been suggested
      in earlier reports. Recent long-term studies suggest an increased association
      ratio of scleroderma and malignancy. However, the underlying mechanisms remain
      elusive. This paper reviews the mechanisms described in earlier studies and
      discusses their possible pathogenetic meaning for the interrelationship and the
      pathogenesis of scleroderma and neoplasia.

PMID- 11978580
TI  - Prospective study of diet and pancreatic cancer in male smokers.
AB  - There have been few prospective studies relating diet to pancreatic cancer, with
      most having fewer than 100 cases and only one examining dietary nutrients. The
      authors prospectively examined dietary factors hypothesized to be associated with
      exocrine pancreatic cancer in the Alpha-Tocopherol, Beta-Carotene Cancer
      Prevention Study cohort in Finland. Of the 27,111 male smokers aged 50-69 years
      with complete dietary information, as ascertained from a self-administered
      dietary history questionnaire given at baseline (1985-1988), 163 developed
      pancreatic cancer from 1985 through November 1997. Cox proportional hazards
      models were used to estimate smoking- and age-adjusted hazard ratios and 95%
      confidence intervals. Energy-adjusted butter consumption and saturated fat intake
      were positively associated with pancreatic cancer (highest quintile vs. lowest:
      hazard ratio (HR) = 1.40, 95% confidence interval (CI): 0.87, 2.25 (p trend =
      0.04), and HR = 1.60, 95% CI: 0.96, 2.64 (p trend = 0.02), respectively). Energy
      intake and energy-adjusted carbohydrate intake were inversely associated with the
      disease (highest quintile vs. lowest: HR = 0.62, 95% CI: 0.36, 1.07 (p trend =
      0.05), and HR = 0.62, 95% CI: 0.37, 1.03 (p trend = 0.02), respectively). These
      results support the hypothesis that a high intake of saturated fat may increase
      the risk of pancreatic cancer in smokers, while greater intakes of energy and
      carbohydrate may reduce the risk.

PMID- 11978581
TI  - Pancreas cancer--we know about smoking, but do we know anything else?

PMID- 11978583
TI  - Environmental arsenic exposure from a coal-burning power plant as a potential
      risk factor for nonmelanoma skin carcinoma: results from a case-control study in
      the district of Prievidza, Slovakia.
AB  - To investigate the risk of arsenic exposure from a coal-burning power plant in
      Slovakia on nonmelanoma skin cancer (NMSC) development, a 1996-1999 population
      based case-control study was conducted with 264 cases and 286 controls. Exposure
      assessment was based on residential history and annual emissions (Asres1, Asres2)
      and on nutritional habits and arsenic content in food (Asnut1, Asnut2). Asres1
      was assessed as a function of the distance of places of residence to the plant.
      Asres2 additionally considered workplace locations. Asnut1 was used to calculate
      arsenic uptake by weighting food frequencies with arsenic concentrations and
      annual consumption of food items. Asnut2 additionally considered consumption of
      local products. Age- and gender-adjusted risk estimates for NMSC in the highest
      exposure category (90th vs. 30th percentile) were 1.90 (95% confidence interval
      (CI): 1.39, 2.60) for Asres1, 1.90 (95% CI: 1.38, 2.62) for Asres2, 1.19 (95% CI:
      0.64, 2.12) for Asnut1, and 1.83 (95% CI: 0.98, 3.43) for Asnut2. No interaction
      was found between arsenic exposure and dietary and residential data. Other plant
      emissions could have confounded the distance-based exposure variables.
      Consumption of contaminated vegetables and fruits could be confounded by the
      protective effects of such a diet. Nevertheless, the authors found an excess NMSC
      risk for environmental arsenic exposure.

PMID- 11978584
TI  - Cancer in Korean war navy technicians: mortality survey after 40 years.
AB  - This study reports on over 40 years of mortality follow-up of 40,581 Navy
      veterans of the Korean War with potential exposure to high-intensity radar. The
      cohort death rates were compared with mortality rates for White US men using
      standardized mortality ratios, and the death rates for men in occupations
      considered a priori to have high radar exposure were compared with the rates for
      men in low-exposure occupations using Poisson regression. Deaths from all
      diseases and all cancers were significantly below expectation overall and for the
      20,021 sailors with high radar exposure potential. There was no evidence of
      increased brain cancer in the entire cohort (standardized mortality ratio (SMR) =
      0.9, 95% confidence interval (CI): 0.7, 1.1) or in high-exposure occupations (SMR
      = 0.7, 95% CI: 0.5, 1.0). Testicular cancer deaths also occurred less frequently
      than expected in the entire cohort and high-exposure occupations. Death rates for
      several smoking-related diseases were significantly lower in the high-exposure
      occupations. Nonlymphocytic leukemia was significantly elevated among men in high
      exposure occupations but in only one of the three high-exposure occupations,
      namely, electronics technicians in aviation squadrons (SMR = 2.2, 95% CI: 1.3,
      3.7). Radar exposure had little effect on mortality in this cohort of US Navy
      veterans.

PMID- 11978585
TI  - Increased atrial fibrillation mortality: United States, 1980-1998.
AB  - The authors used death certificate data to evaluate national trends in the
      reporting of atrial fibrillation as an underlying or contributory cause of death
      for groups defined by age (45 years or older), sex, and race (Black vs. White)
      and to examine comorbidity. The multiple-causes mortality files from 1980 through
      1998 were analyzed for decedents, with atrial fibrillation (International
      Classification of Diseases, Ninth Revision, code 427.3) listed as one of up to 20
      conditions causing death. The number of decedents with atrial fibrillation
      increased from 18,947 in 1980 to 61,946 in 1998, and the proportion with atrial
      fibrillation reported as the underlying cause of death rose from 8.3% in 1980 to
      11.6% in 1998. Age-standardized death rates from 1980 to 1998 were consistently
      highest among White men, followed (in descending order) by White women, Black
      men, and Black women. Overall, the age-standardized rate (per 100,000) increased
      from 27.6 in 1980 to 69.8 in 1998 (an average annual increase of 5.4%, p <
      0.0001). Ischemic heart disease was the most frequent underlying cause of death
      among decedents with atrial fibrillation (26.8%). These findings emphasize the
      need for increased application of proven prevention and control measures to
      decrease associated cardiovascular morbidity and mortality.

PMID- 11978586
TI  - Water, other fluids, and fatal coronary heart disease: the Adventist Health
      Study.
AB  - Whole blood viscosity, plasma viscosity, hematocrit, and fibrinogen are
      considered independent risk factors for coronary heart disease and can be
      elevated by dehydration. The associations between fatal coronary heart disease
      and intake of water and fluids other than water were examined among the 8,280
      male and 12,017 female participants aged 38-100 years who were without heart
      disease, stroke, or diabetes at baseline in 1976 in the Adventist Health Study, a
      prospective cohort study. A total of 246 fatal coronary heart disease events
      occurred during the 6-year follow-up. High daily intakes of water (five or more
      glasses) compared with low (two or fewer glasses) were associated with a relative
      risk in men of 0.46 (95% confidence interval (CI): 0.28, 0.75; p trend = 0.001)
      and, in women, of 0.59 (95% CI: 0.36, 0.97). A high versus low intake of fluids
      other than water was associated with a relative risk of 2.47 (95% CI: 1.04, 5.88)
      in women and of 1.46 (95% CI: 0.7, 3.03) in men. All associations remained
      virtually unchanged in multivariate analysis adjusting for age, smoking,
      hypertension, body mass index, education, and (in women only) hormone replacement
      therapy. Fluid intake as a putative coronary heart disease risk factor may
      deserve further consideration in other populations or using other study designs.

PMID- 11978587
TI  - Hyperproinsulinemia and proinsulin-to-insulin ratios in Swedish middle-aged men:
      association with glycemia and insulin resistance but not with family history of
      diabetes.
AB  - Elevated proinsulin and proinsulin/insulin ratios are features of abnormal beta
      cell function in type 2 diabetes. The participation of genetic factors is
      disputed. The authors wished to investigate relations between family history of
      diabetes on one hand and proinsulin as well as proinsulin/immunoreactive insulin
      ratios on the other. A large, population-based sample of Swedish men aged 35-54
      years in 1992 was studied. Subjects without known diabetes were selected either
      to have a strong family history of diabetes (n = 1,619) or no history of the
      disease (n = 1,495). An oral glucose tolerance test detected 172 subjects with
      impaired glucose tolerance and 55 subjects with previously unknown diabetes
      according to World Health Organization 1985 criteria. In multiple regression
      analysis, fasting levels of proinsulin and proinsulin/insulin ratios were
      positively associated both with the 2-hour glucose level (as a continuous
      variable) and with obesity, whereas a negative association was found with birth
      weight. No association was found with family history of diabetes or with
      chronologic age. These findings indicate that elevated proinsulin and
      proinsulin/insulin ratios are secondary to increased demands on beta-cell
      secretion induced by hyperglycemia and insulin resistance with no discernible
      influence of family history of diabetes.

PMID- 11978588
TI  - Lipids and pulmonary function in the Third National Health and Nutrition
      Examination Survey.
AB  - Studies considering the association between total cholesterol and
      noncardiovascular mortality, particularly from respiratory disease, yield
      inconclusive findings. To explore this question, the relation of lipids to
      pulmonary function, specifically forced expiratory volume in 1 second (FEV(1)),
      was investigated in the Third National Health and Nutrition Examination Survey.
      Conducted in the United States in 1988-1994 among adults aged > or =17 years,
      this survey measured serum lipids, FEV(1), and confounding factors including
      smoking and antioxidants. Multiple linear regression analysis explored the
      relation of FEV(1)/height(2) to low density lipoprotein (LDL) cholesterol, high
      density lipoprotein (HDL) cholesterol, and their respective apolipoproteins (apo)
      B and A-I. A standard deviation increase in HDL cholesterol or apo A-I was
      associated with an FEV(1) increase of 43 ml (95% confidence interval (CI): 30,
      56) or 29 ml (95% CI: 11, 47), respectively, for an average-height adult. A
      standard deviation increase in LDL cholesterol or apo B was associated with an
      FEV(1) decrease of -24 ml (95% CI: -43, -5) or -53 ml (95% CI: -74, -32),
      respectively, adjusted for serum antioxidant status. The lipid subfractions were
      differentially associated with FEV(1) consistent with the possibility that LDL
      cholesterol contributes to endogenous oxidative burden while HDL cholesterol
      attenuates inflammatory tissue damage. Whether these associations are causal
      remains to be determined.

PMID- 11978589
TI  - Birth size, growth, and blood pressure between the ages of 7 and 26 years:
      failure to support the fetal origins hypothesis.
AB  - The "fetal origins hypothesis" asserts that birth weight is inversely related to
      later blood pressure. Data from a cohort of 891 infants born in Dunedin, New
      Zealand, in 1972-1973 whose blood pressure was measured at 2-year intervals from
      age 7 years to age 15 years and at ages 18 and 26 years were used to test this
      hypothesis. Three regression models based on standardized scores for weight and
      height were used. The first showed that at any of the ages at which the cohort
      was assessed, an increase in birth weight of one z score (one standard deviation)
      was commensurate with a decrease of 0.29 mmHg (95% confidence interval: -0.17,
      0.76) in blood pressure. The second model showed that a one-z-score increase in
      weight between birth and a subsequent age was associated with an increase in
      systolic blood pressure of 0.96 mmHg (95% confidence interval: 0.53, 1.38). This
      estimate applied to all ages. The third model showed that the effect of an
      interaction between birth weight and later weight was not significant; thus,
      there was no evidence to suggest that children with a low birth weight who became
      overweight or obese had extra high blood pressure. Similar results were obtained
      for height. These results fail to support the fetal origins hypothesis.

PMID- 11978590
TI  - Intake of wine, beer, and spirits and the risk of clinical common cold.
AB  - To examine whether intakes of wine, beer, spirits, and total alcohol are
      associated with the risk of common cold, in 1998-1999 the authors analyzed data
      from a cohort study carried out in a population of 4,272 faculty and staff of
      five Spanish universities. Usual alcohol intake was assessed at baseline by means
      of a standardized frequency questionnaire that was validated in a random sample
      of the population. The authors detected 1,353 cases of common cold. Total alcohol
      intake and beer and spirits consumption were not related to the occurrence of
      common cold, whereas consumption of wine was inversely associated with the risk
      of common cold. When drinkers of >14 glasses of wine per week were compared with
      teetotalers, the relative risk was 0.6 (95% confidence interval: 0.4, 0.8) after
      adjustment for age, sex, and faculty/staff status. The association was stronger
      for red wine. These results remained unaltered after adjustment for total alcohol
      intake and for other potential risk factors for common cold. Findings suggest
      that wine intake, especially red wine, may have a protective effect against
      common cold. Beer, spirits, and total alcohol intakes do not seem to affect the
      incidence of common cold.

PMID- 11978592
TI  - Completeness of notifiable infectious disease reporting in the United States: an
      analytical literature review.
AB  - Despite state and local laws requiring medical providers to report notifiable
      infectious diseases to public health authorities, reporting is believed to be
      incomplete. Through means of an analytical literature review, the authors
      synthesize current knowledge on the completeness of disease reporting and
      identify factors associated with reporting completeness. The review was limited
      to published studies, conducted in the United States between 1970 and 1999, that
      quantitatively assessed infectious disease reporting completeness. Thirty-three
      studies met the inclusion criteria. Reporting completeness, expressed between 0%
      and 100%, was treated as the dependent outcome variable in statistical analysis;
      disease, study location, time period, study design, and study size were treated
      as independent variables. Fifty-six distinct measures of reporting completeness
      were identified for 21 diseases. Reporting completeness varied from 9% to 99% and
      was most strongly associated with the disease being reported. The mean reporting
      completeness for acquired immunodeficiency syndrome, sexually transmitted
      diseases, and tuberculosis as a group was significantly higher (79%) than for all
      other diseases combined (49%) (p < 0.01).

PMID- 11978591
TI  - Impact of case ascertainment on recent trends in diabetes incidence in Rochester,
      Minnesota.
AB  - The authors previously reported an increase in the incidence of diabetes mellitus
      among Rochester, Minnesota, residents during the period 1970-1989. This study
      provides updated rates from data collected through 1994. Trends in diabetes
      surveillance, i.e., the proportion of residents who had a blood glucose
      measurement in each year between 1987 and 1994, are also provided. The authors
      reviewed medical records to identify residents aged 30 years or more who first
      met National Diabetes Data Group criteria for diabetes between January 1, 1970,
      and December 31, 1994. Age- and sex-adjusted incidence rates were calculated for
      successive quinquennia (5-year periods), and Poisson regression was used to test
      for an effect of calendar year; calendar period (1970-1989 vs. 1990-1994) was
      added to assess whether the association with calendar year varied in the most
      recent quinquennium. Altogether, 1,992 Rochester residents first met National
      Diabetes Data Group criteria for diabetes between 1970 and 1994. The age-adjusted
      incidence per 100,000 person-years increased 67% for males (267.0 vs. 444.8) and
      42% for females (225.4 vs. 319.1) between 1970-1974 and 1990-1994. Calendar year
      (p < 0.001) and calendar period (p = 0.026) were significant, suggesting that
      rates accelerated during 1990-1994. The proportion of residents with at least one
      blood glucose measurement per year was unchanged (p = 0.181) from 1987 to 1994,
      while the incidence of diabetes increased (p = 0.033). Thus, the authors conclude
      that the increase in diabetes incidence accelerated over the last quinquennium
      and was not due to increased surveillance.

PMID- 11978593
TI  - Ascertainment bias in family-based case-control studies.
AB  - In a family-matched case-control study, a population-based sample of cases is
      selected from a well-defined geographic region over a fixed period of time. For
      diseases of adult onset, the control is generally a sibling or cousin who is
      matched on sex and age without regard to location of residence. Such a design can
      lead to biased estimates of environmental relative risk if the prevalence of an
      environmental risk factor varies by the geographic region from which the cases
      and controls are drawn. However, assuming the independence of genotype and
      environmental exposure, the estimators for the gene and gene-environment
      interaction effects are consistent. This suggests that we must use caution in
      interpreting parameters that estimate environmental main effects from a family
      based case-control study if controls are selected from outside the case
      ascertainment region.

PMID- 11978594
TI  - Prenatal exclusion of recessively inherited disorders: should maternal plasma
      analysis precede invasive techniques?

PMID- 11978595
TI  - Errors in laboratory medicine.
AB  - BACKGROUND: The problem of medical errors has recently received a great deal of
      attention, which will probably increase. In this minireview, we focus on this
      issue in the fields of laboratory medicine and blood transfusion. METHODS: We
      conducted several MEDLINE queries and searched the literature by hand. Searches
      were limited to the last 8 years to identify results that were not biased by
      obsolete technology. In addition, data on the frequency and type of preanalytical
      errors in our institution were collected. RESULTS: Our search revealed large
      heterogeneity in study designs and quality on this topic as well as relatively
      few available data and the lack of a shared definition of "laboratory error"
      (also referred to as "blunder", "mistake", "problem", or "defect"). Despite these
      limitations, there was considerable concordance on the distribution of errors
      throughout the laboratory working process: most occurred in the pre- or
      postanalytical phases, whereas a minority (13-32% according to the studies)
      occurred in the analytical portion. The reported frequency of errors was related
      to how they were identified: when a careful process analysis was performed,
      substantially more errors were discovered than when studies relied on complaints
      or report of near accidents. CONCLUSIONS: The large heterogeneity of literature
      on laboratory errors together with the prevalence of evidence that most errors
      occur in the preanalytical phase suggest the implementation of a more rigorous
      methodology for error detection and classification and the adoption of proper
      technologies for error reduction. Clinical audits should be used as a tool to
      detect errors caused by organizational problems outside the laboratory.

PMID- 11978596
TI  - Cystatin C: an improved estimator of glomerular filtration rate?
AB  - BACKGROUND: Glomerular filtration rate (GFR) is routinely assessed by measuring
      the concentrations of endogenous serum markers such as blood urea nitrogen and
      serum creatinine (SCr). Although widely used, these endogenous markers are not
      ideal and do not perform optimally in certain clinical settings. The purpose of
      this review is to critically review the potential utility of cystatin C (CysC),
      especially in patient populations in which CysC may have an advantage over
      routinely used endogenous markers of GFR. APPROACH: In a narrative approach, we
      extensively review publications, primarily from the last 5 years, that address
      the development of methods to measure CysC, reference intervals, and the
      diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001
      Medline was searched using "cystatin c" as a textword, and articles that examined
      >75 individuals (except for renal transplant studies) and/or used accepted "gold
      standards" for assessing GFR were selected for inclusion. A total of 17 studies
      are reviewed that provide reference interval data for several populations. A
      total of 24 studies make conclusions about the utility of CysC vs SCr and/or
      creatinine clearance, with 20 providing data on the sensitivity and specificity
      of CysC for detecting impaired GFR. These publications are organized into
      subgroups that deal with specific patient populations or clinical situations.
      CONTENT: This review focuses on two areas: (a) the evolution of immunoassays used
      to determine the concentration of CysC in serum, their analytic sensitivity, and
      reference intervals; and (b) the diagnostic performance of CysC against other
      renal markers in the general population and in specific subpopulations of
      patients. SUMMARY: Studies of reference intervals for CysC overwhelmingly
      demonstrated that CysC values in blood are independent of age and sex. Of the 24
      studies that examined clinical utility, 15 concluded that CysC is superior to
      SCr, whereas 9 concluded that CysC is equivalent but provides no advantage.
      Summary ROC plot analysis of 20 studies that provide sensitivity and specificity
      data strongly suggests that CysC will be superior to SCr for detecting impaired
      GFR. Taken together, it is clear that CysC performs at least as well as SCr in
      the population at large and that it is likely to be superior to SCr in specific
      patient populations.

PMID- 11978597
TI  - Metabolic, nutritional, iatrogenic, and artifactual sources of urinary organic
      acids: a comprehensive table.
AB  - BACKGROUND: The determination of organic acids and glycine conjugates in urine is
      key for the diagnosis and follow-up of several inborn errors of metabolism (IEM).
      However, clinical interpretations may still be hindered by ambiguity in the
      sources of some urinary organic acids and acylglycines as well as in the
      relationship between their excretion and IEM. APPROACH: Relevant data have been
      compiled from major books and references on the topic and by exhaustive
      bibliographic searches through the Medline and Current Contents databases.
      CONTENT: A comprehensive table has been designed according to organic acids and
      conjugates. This table is intended to assist in the interpretation of organic
      acid profiles because, in addition to IEM, it also refers to other pathologic
      causes and to physiologic, nutritional, iatrogenic, and artifactual sources. Some
      preanalytical issues, including possible misinterpretations, are reviewed with
      regard to IEM.

PMID- 11978598
TI  - Use of constant denaturant capillary electrophoresis of pooled blood samples to
      identify single-nucleotide polymorphisms in the genes (Scnn1a and Scnn1b)
      encoding the alpha and beta subunits of the epithelial sodium channel.
AB  - BACKGROUND: The epithelial sodium channel (ENaC) is composed of three homologous
      subunits: alpha, beta, and gamma. Mutations in the Scnn1b and Scnn1g genes, which
      encode the beta and the gamma subunits of ENaC, cause a severe form of
      hypertension (Liddle syndrome). The contribution of genetic variants within the
      Scnn1a gene, which codes for the alpha subunit, has not been investigated.
      METHODS: We screened for mutations in the COOH termini of the alpha and beta
      subunits of ENaC. Blood from 184 individuals from 31 families participating in a
      study on the genetics of hypertension were analyzed. Exons 13 of Scnn1a and
      Scnn1b, which encode the second transmembrane segment and the COOH termini of
      alpha- and beta-ENaC, respectively, were amplified from pooled DNA samples of
      members of each family by PCR. Constant denaturant capillary electrophoresis
      (CDCE) was used to detect mutations in PCR products of the pooled DNA samples.
      RESULTS: The detection limit of CDCE for ENaC variants was 1%, indicating that
      all members of any family or up to 100 individuals can be analyzed in one CDCE
      run. CDCE profiles of the COOH terminus of alpha-ENaC in pooled family members
      showed that the 31 families belonged to four groups and identified families with
      genetic variants. Using this approach, we analyzed 31 rather than 184 samples.
      Individual CDCE analysis of members from families with different pooled CDCE
      profiles revealed five genotypes containing 1853G-->T and 1987A-->G
      polymorphisms. The presence of the mutations was confirmed by DNA sequencing. For
      the COOH terminus of beta-ENaC, only one family showed a different CDCE profile.
      Two members of this family (n = 5) were heterozygous at 1781C-->T (T594M).
      CONCLUSION: CDCE rapidly detects point mutations in these candidate disease
      genes.

PMID- 11978599
TI  - Beta-trace protein, cystatin C, beta(2)-microglobulin, and creatinine compared
      for detecting impaired glomerular filtration rates in children.
AB  - BACKGROUND: Because of the limitations of serum creatinine as a marker of
      glomerular filtration rate (GFR) in children, we assessed the diagnostic accuracy
      of the novel marker beta-trace protein (BTP) in comparison with cystatin C (Cys
      C), beta(2)-microglobulin (beta(2)-MG), and creatinine as conventional indicators
      of reduced GFR. METHODS: We obtained serum samples from 225 children (age range,
      0.2-18 years) with various renal pathologies who were referred for nuclear
      medicine clearance investigations (technetium-diethylenetriamine pentaacetic acid
      or chromium-EDTA). We measured Cys-C, BTP (nephelometric tests; Dade Behring),
      beta(2)-MG (Tinaquant; Roche), and creatinine (enzymatic assay; Creatinine-PAP;
      Roche). RESULTS: Seventy-five children had reduced GFR (<90 mL x min(-1) x 1.73
      m(-2)). One hundred fifty children (independent of gender and age) with values
      >90 mL x min(-1) x 1.73 m(-2) comprised the control group with gaussian
      distributions of BTP and Cys-C concentrations. The upper reference limits (97.5
      percentile) were 1.01 mg/L for BTP and 1.20 mg/L for Cys-C. The correlations of
      nuclear medicine clearance with the reciprocals of BTP, Cys-C, and the Schwartz
      GFR estimate were significantly higher (r = 0.653, 0.765, and 0.706,
      respectively; P <0.05) than with the reciprocal of creatinine or beta(2)-MG (r =
      0.500 and 0.557, respectively). ROC analysis showed a significantly higher
      diagnostic accuracy of BTP, Cys-C, and the GFR estimate for the detection of
      impaired GFR than serum creatinine (P <0.05). Compared to creatinine, BTP
      increased the diagnostic sensitivity by approximately 30%, but it was not more
      sensitive than Cys-C or the Schwartz GFR estimate. CONCLUSIONS: BTP is superior
      to serum creatinine and an alternative for Cys-C to detect mildly reduced GFR in
      children, but it is not better than the Schwartz GFR estimate.

PMID- 11978600
TI  - Highly sensitive cholesterol assay with enzymatic cycling applied to measurement
      of remnant lipoprotein-cholesterol in serum.
AB  - BACKGROUND: Remnant lipoprotein-cholesterol (RLP-C) concentrations in sera of
      healthy individuals are very low (0.080-0.437 mmol/L), making conventional
      cholesterol methods poorly suited to this purpose. We have developed a highly
      sensitive cholesterol assay (CD method) and applied it to the RLP-C assay.
      METHODS: The CD shuttled cholesterol reversibly between reduced and oxidized
      forms in the presence of thio-NAD and NADH. The production rate of thio-NADH
      correlated with the cholesterol concentration and was measured by the absorbance
      at 404/500 nm. This CD method was combined with an immunoaffinity separation
      procedure with specific monoclonal antibodies to apolipoprotein (apo) A1 and apo
      B-100 and used for RLP-C assay. Results were compared with a RLP-C method that
      uses cholesterol oxidase, peroxidase, and chromogenic substrate. RESULTS: The CD
      method could detect 0.10 x 10(-3) mmol/L cholesterol and was at least 5 times
      more sensitive than the conventional enzymatic method. Within- and between-day
      imprecision (as CVs) of the RLP-C assay with the CD method was <4%. Regression
      analysis of RLP-C assays with the new (y) and conventional (x) cholesterol
      methods yielded: y = 1.02x - 0.008 mmol/L (S(y/x) = 0.0065 mmol/L; r = 0.997; n =
      297). CONCLUSIONS: Serum RLP-C can be measured by the CD method. The CD method
      may be useful for other assays that require sensitive cholesterol measurements in
      biological materials.

PMID- 11978601
TI  - Blood glutathione disulfide: in vivo factor or in vitro artifact?
AB  - BACKGROUND: The reported mean concentration of glutathione disulfide (GSSG) in
      human blood/erythrocytes varies widely (1 to >500 micromol/L), as does that of
      reduced glutathione (GSH) to a lesser extent. We have identified and investigated
      possible pitfalls in measurement of both GSH and GSSG. METHODS: We measured GSH
      and GSSG using a spectrophotometer with a modification of the GSH recycling
      method; the same samples were also measured by reversed-phase HPLC after
      derivatization of thiols (dithiothreitol was used to reduce disulfides) with
      monobromobimane. The thiol-bimane adduct was measured by a fluorescence detector.
      RESULTS: Measured GSH/GSSG concentrations were affected by the following: (a)
      oxidation of thiols in acidified samples; (b) oxidation after restoring neutral
      alkaline pH; (c) oxidation during acid deproteinization; (d) shift in the
      GSH/GSSG equilibrium because of irreversible blocking of free thiols; and (e)
      reaction of electrophiles with amino groups. In particular, oxidation during
      sample deproteinization with acid influenced and produced artifacts (30-150
      micromol/L GSSG was produced by this procedure); this phenomenon was directly
      correlated with the presence of oxygenated hemoglobin, being minimized by both
      oxygen deprivation and incubation in an atmosphere of 5% carbon monoxide.
      CONCLUSIONS: GSSG is present in healthy human blood at low concentrations (2-6
      micromol/L), and most published data on GSSG may be affected by artifacts.

PMID- 11978602
TI  - Changes in bone turnover in patients with anorexia nervosa during eleven weeks of
      inpatient dietary treatment.
AB  - BACKGROUND: Many adolescents with anorexia nervosa suffer from severe osteopenia
      and osteoporosis. We hypothesized that individualized nutrition therapy may
      improve bone turnover in anorectic patients. METHODS: We studied 19 female
      patients [mean age, 14.2 +/- 1.4 years; mean body weight, 39.3 +/- 5.4 kg; mean
      body mass index (BMI), 14.2 +/- 1.4 kg/m(2)] with anorexia nervosa (International
      Classification of Diseases-10: F50.0, F50.1) for a period of 3 months. Nutrition
      therapy began at the end of the first week and included individualized
      hypercaloric diets, high calcium intake (2000 mg/day), and administration of
      vitamin D (400 IU/day). Blood samples were taken at baseline and again in weeks
      3, 7, and 11. We measured serum calcium, parathyroid hormone, bone formation and
      resorption markers, insulin-like growth factor 1 (IGF-1), and leptin. RESULTS:
      Mean BMI increased significantly, from 14.2 +/- 1.4 to 17.1 +/- 0.7 kg/m(2) (P =
      0.000001), during the course of treatment, whereas serum total calcium and
      phosphate concentrations remained unchanged. The bone formation markers
      procollagen-I carboxy-terminal propeptide and bone alkaline phosphatase almost
      doubled (P = 0.006). Both IGF-1 (P = 0.00001) and leptin (P = 0.000005) increased
      significantly by week 11. Parallel to this, the serum concentration of C
      telopeptide, a bone resorption marker, decreased significantly (P = 0.009).
      CONCLUSIONS: Nutritional rehabilitation, possibly as a result of increasing IGF-1
      and leptin concentrations, may increase bone formation. It therefore provides
      additional objective evidence of the importance of nutrition for bone.

PMID- 11978603
TI  - Assessment of the diagnostic accuracy of the TDx-FLM II to predict fetal lung
      maturity.
AB  - BACKGROUND: Because respiratory distress syndrome (RDS) affects 1% of live
      births, accurate and rapid assessment of markers of fetal lung maturity is
      critical to clinicians in deciding whether to deliver a preterm infant. Our
      objective was to determine the optimal diagnostic cutoff value for the TDx-FLM II
      assay (Abbott Laboratories) for predicting clinically significant RDS. METHODS:
      Amniotic fluid TDx-FLM II data were collected retrospectively over 4 years. Women
      were included in the study if they had delivered within 72 h of TDx-FLM II
      testing and both the mother and infant charts could be reviewed. Women who had
      been treated with steroids and delivered unaffected infants were excluded from
      the analysis. The diagnosis of RDS was defined as infants who either were treated
      with surfactant and/or were placed on a ventilator and/or required continuous
      positive airway pressure for >1 day. RESULTS: A total of 185 women met all entry
      criteria (15 RDS, 170 non-RDS). A cutoff value for a mature result of >or=45 mg/g
      gave a sensitivity of 100% (95% confidence interval, 82-100%) and a specificity
      of 90% (95% confidence interval, 78-89%). CONCLUSIONS: The TDx-FLM II appears to
      predict clinically significant RDS when a cutoff of >or=45 mg/g is used for
      mature results. Further studies will be required to confirm these findings.

PMID- 11978604
TI  - Parathyroid hormone is more stable in EDTA plasma than in serum.

PMID- 11978605
TI  - Denaturing gradient gel electrophoresis for the molecular characterization of six
      patients with guanidinoacetate methyltransferase deficiency.

PMID- 11978606
TI  - HFE genotyping by amplification refractory mutation system-denaturing HPLC.

PMID- 11978607
TI  - New nuclear encoded mitochondrial mutation illustrates pitfalls in prenatal
      diagnosis by biochemical methods.

PMID- 11978608
TI  - Complete sequencing of a genetic polymorphism in NAT2 in the Korean population.

PMID- 11978609
TI  - Noninvasive prenatal exclusion of congenital adrenal hyperplasia by maternal
      plasma analysis: a feasibility study.

PMID- 11978610
TI  - Unusual late onset of X-linked chronic granulomatous disease in an adult woman
      after unsuspicious childhood.

PMID- 11978611
TI  - Hemolytic uremic syndrome attributable to Streptococcus pneumoniae infection: a
      novel cause for secondary protein N-glycan abnormalities.

PMID- 11978612
TI  - Can glycohemoglobin be used to assess glycemic control in patients with chronic
      renal failure?

PMID- 11978613
TI  - Estimation of true calcium absorption in men.

PMID- 11978614
TI  - Sensitive immunoluminometric assay for the detection of procalcitonin.

PMID- 11978615
TI  - Comparison of cardiac troponin I in serum and heparin plasma with the dimension
      RxL assay.

PMID- 11978616
TI  - Reforming laboratory reimbursement: issues, impact and innovations. A summary of
      the clinical chemistry forum held on November 15, 2001.

PMID- 11978617
TI  - Increased homocysteine in liver cirrhosis: a result of renal impairment?

PMID- 11978618
TI  - Variability in potassium/hemoglobin ratios for hemolysis correction.

PMID- 11978619
TI  - Lack of association of the -1171 (5A) allele of the MMP3 promoter with breast
      cancer.

PMID- 11978620
TI  - Application of the Bland-Altman plot for interpretation of method-comparison
      studies: a critical investigation of its practice.

PMID- 11978625
TI  - The ryanodine receptor calcium channel of beta-cells: molecular regulation and
      physiological significance.
AB  - The list of Ca(2+) channels involved in stimulus-secretion coupling in beta-cells
      is increasing. In this respect the roles of the voltage-gated Ca(2+) channels and
      IP(3) receptors are well accepted. There is a lack of consensus about the
      significance of a third group of Ca(2+) channels called ryanodine (RY) receptors.
      These are large conduits located on Ca(2+) storage organelle. Ca(2+) gates these
      channels in a concentration- and time-dependent manner. Activation of these
      channels by Ca(2+) leads to fast release of Ca(2+) from the stores, a process
      called Ca(2+)-induced Ca(2+) release (CICR). A substantial body of evidence
      confirms that beta-cells have RY receptors. CICR by RY receptors amplifies Ca(2+)
      signals. Some properties of RY receptors ensure that this amplification process
      is engaged in a context-dependent manner. Several endogenous molecules and
      processes that modulate RY receptors determine the appropriate context. Among
      these are several glycolytic intermediates, long-chain acyl CoA, ATP, cAMP,
      cADPR, NO, and high luminal Ca(2+) concentration, and all of these have been
      shown to sensitize RY receptors to the trigger action of Ca(2+). RY receptors,
      thus, detect co-incident signals and integrate them. These Ca(2+) channels are
      targets for the action of cAMP-linked incretin hormones that stimulate glucose
      dependent insulin secretion. In beta-cells some RY receptors are located on the
      secretory vesicles. Thus, despite their low abundance, RY receptors are emerging
      as distinct players in beta-cell function by virtue of their large conductance,
      strategic locations, and their ability to amplify Ca(2+) signals in a context
      dependent manner.

PMID- 11978626
TI  - Prevention of overt hypoglycemia during exercise: stimulation of endogenous
      glucose production independent of hepatic catecholamine action and changes in
      pancreatic hormone concentration.
AB  - These studies were conducted to determine the magnitude and mechanism of
      compensation for impaired glucagon and insulin responses to exercise. For this
      purpose, dogs underwent surgery >16 days before experiments, at which time flow
      probes were implanted and silastic catheters were inserted. During experiments,
      glucagon and insulin were fixed at basal levels during rest and exercise using a
      pancreatic clamp with glucose clamped (PC/GC; n = 5), a pancreatic clamp with
      glucose unclamped (PC; n = 7), or a pancreatic clamp with glucose unclamped +
      intraportal propranolol and phentolamine hepatic alpha- and beta-adrenergic
      receptor blockade (PC/HAB; n = 6). Glucose production (R(a)) was measured
      isotopically. Plasma glucose was constant in PC/GC, but fell from basal to
      exercise in PC and PC/HAB. R(a) was unchanged with exercise in PC/GC, but was
      slightly increased during exercise in PC and PC/HAB. Despite minimal increases in
      epinephrine in PC/GC, epinephrine increased approximately sixfold in PC and
      PC/HAB during exercise. In summary, during moderate exercise, 1) the increase in
      R(a) is absent in PC/GC; 2) only a moderate fall in arterial glucose occurs in
      PC, due to a compensatory increase in R(a); and 3) the increase in R(a) is
      preserved in PC/HAB. In conclusion, stimulation of R(a) by a mechanism
      independent of pancreatic hormones and hepatic adrenergic stimulation is a
      primary defense against overt hypoglycemia.

PMID- 11978627
TI  - Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates
      expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB
      activation by TNF-alpha is obligatory.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a contributing cause of the insulin
      resistance seen in obesity and obesity-linked type 2 diabetes, but the
      mechanism(s) by which TNF-alpha induces insulin resistance is not understood. By
      using 3T3-L1 adipocytes and oligonucleotide microarrays, we identified 142 known
      genes reproducibly upregulated by at least threefold after 4 h and/or 24 h of TNF
      alpha treatment, and 78 known genes downregulated by at least twofold after 24 h
      of TNF-alpha incubation. TNF-alpha-induced genes include transcription factors
      implicated in preadipocyte gene expression or NF-kappaB activation, cytokines and
      cytokine-induced proteins, growth factors, enzymes, and signaling molecules.
      Importantly, a number of adipocyte-abundant genes, including GLUT4, hormone
      sensitive lipase, long-chain fatty acyl-CoA synthase, adipocyte complement
      related protein of 30 kDa, and transcription factors CCAAT/enhancer binding
      protein-alpha, receptor retinoid X receptor-alpha, and peroxisome profilerator
      activated receptor gamma were significantly downregulated by TNF-alpha treatment.
      Correspondingly, 24-h exposure of 3T3-L1 adipocytes to TNF-alpha resulted in
      reduced protein levels of GLUT4 and several insulin signaling proteins, including
      the insulin receptor, insulin receptor substrate 1 (IRS-1), and protein kinase B
      (AKT). Nuclear factor-kappaB (NF-kappaB) was activated within 15 min of TNF-alpha
      addition. 3T3-L1 adipocytes expressing IkappaBalpha-DN, a nondegradable NF-kappaB
      inhibitor, exhibited normal morphology, global gene expression, and insulin
      responses. However, absence of NF-kappaB activation abolished suppression of >98%
      of the genes normally suppressed by TNF-alpha and induction of 60-70% of the
      genes normally induced by TNF-alpha. Moreover, extensive cell death occurred in
      IkappaBalpha-DN-expressing adipocytes after 2 h of TNF-alpha treatment. Thus the
      changes in adipocyte gene expression induced by TNF-alpha could lead to insulin
      resistance. Further, NF-kappaB is an obligatory mediator of most of these TNF
      alpha responses.

PMID- 11978628
TI  - Effects of acute and chronic administration of the melanocortin agonist MTII in
      mice with diet-induced obesity.
AB  - High-fat diet-induced obesity (DIO) in rodents is associated with hyperleptinemia
      and resistance to leptin, but the response to agents acting downstream of leptin
      receptors remains unknown. We assessed the response of mice with DIO to treatment
      with MTII, an alpha-melanocyte-stimulating hormone analog. MTII delivered four
      times daily by intraperitoneal injection to C57BL/6J mice produced a dose
      responsive effect on food intake, body weight, leptin, corticosterone, insulin,
      and free fatty acids. In DIO mice, administration of MTII 100 microg q.i.d. i.p.
      markedly suppressed feeding during the first 4 days of treatment, with food
      intake returning to control levels at day 5. Progressive weight loss also
      occurred over the first 4 days, after which weight plateaued at a level below
      control. After 8 days of treatment, MTII-treated DIO mice had major suppression
      of both leptin and insulin levels. Central administration of MTII for 4 days (10
      nmol/day) in DIO mice significantly suppressed food intake, induced weight loss,
      and increased energy expenditure. These results indicate that 1) MTII
      administration to DIO mice causes suppression of food intake and body weight
      loss, and decreased food intake is primarily responsible for weight loss; 2)
      peripheral MTII improves insulin resistance in DIO mice; 3) "tachyphylaxis" to
      the effect of chronic MTII treatment on food intake occurs; and 4) at least some
      of the effects of MTII are exerted centrally. In conclusion, treatment with a
      melanocortin agonist is a promising therapeutic approach to DIO and associated
      insulin resistance.

PMID- 11978630
TI  - Leptin accelerates autoimmune diabetes in female NOD mice.
AB  - We have recently shown that leptin, the product of the obese gene, can directly
      influence T-cell function. In the work presented here, we explored the role of
      leptin in the development of spontaneous autoimmunity in the nonobese diabetic
      (NOD) mouse, an animal model for the study of human insulin-dependent diabetes
      mellitus (type 1 diabetes). We found that expression of serum leptin increased
      soon before the onset of hyperglycemia and diabetes in susceptible females. A
      pathogenetic role of leptin was assessed by administering recombinant leptin to
      young female and male NOD mice. Intraperitoneal injections of leptin accelerated
      autoimmune destruction of insulin-producing beta-cells and significantly
      increased interferon-gamma production in peripheral T-cells. These findings
      indicate that leptin can favor proinflammatory cell responses and directly
      influence development of autoimmune disease mediated by Th1 responses.

PMID- 11978629
TI  - Genetic effects on age-dependent onset and islet cell autoantibody markers in
      type 1 diabetes.
AB  - Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and
      CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells
      were determined by logistic regression analysis in 971 incident patients with
      type 1 diabetes and 702 control subjects aged 0-34 years. GADAs were associated
      with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to
      insulin were negatively associated with age (P < 0.0001) but positively
      associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible
      immune tolerance induction. ICA512/IA-2 were negatively associated with age (P <
      0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04).
      Males were more likely than females to be negative for GADA (P < 0.0001),
      autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P =
      0.004). The CTLA-4 3' end microsatellite marker was not associated with any of
      the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and
      INS VNTR need to be combined with islet autoantibody markers when evaluating the
      risk for type 1 diabetes development.

PMID- 11978631
TI  - Decreased vascular density in mouse pancreatic islets after transplantation.
AB  - An adequate revascularization is crucial for islet survival and function after
      transplantation. Previous studies have suggested that islet revascularization is
      concluded within 14 days after transplantation. We investigated if the vascular
      density of transplanted islets and endogenous pancreatic islets differs. Cultured
      islets were syngeneically transplanted into the kidney, liver, or spleen of
      C57BL/6 mice. One month later, the graft-bearing organ was removed, and
      histological specimens were prepared and stained for endothelium with the lectin
      Bandeiraea simplicifolia. Pancreata from nontransplanted control animals were
      prepared similarly. Uniform staining of endothelium within the grafts and
      endogenous islets was obtained. The vascular density was markedly decreased in
      transplanted islets at all implantation sites, but preferentially in islets
      implanted into the spleen. The vascular density in the connective tissue
      surrounding the transplanted islets was very high compared with that of graft
      intra-islet capillaries. A much lower vascular density was detected in connective
      tissue surrounding implanted microspheres of a size similar to the islets, which
      suggests that the islets per se induced blood vessel formation in their vicinity.
      We conclude that the vascular density in revascularized transplanted islets is
      markedly decreased compared with endogenous islets. This has potential
      implications for islet graft metabolism and function.

PMID- 11978632
TI  - A 1alpha,25-dihydroxyvitamin D(3) analog enhances regulatory T-cells and arrests
      autoimmune diabetes in NOD mice.
AB  - Type 1 diabetes is a chronic progressive autoimmune disease characterized by
      mononuclear cell infiltration, dominated by interleukin-12 (IL-12)-dependent Th1
      cells, of the pancreatic islets, with subsequent destruction of insulin-producing
      beta-cells. Here, we demonstrate that treatment of adult nonobese diabetic (NOD)
      mice with an analog of 1alpha,25-dihydroxyvitamin D(3), an immunomodulatory agent
      preventing dendritic cell maturation, decreases lipopolysaccharide-induced IL-12
      and gamma-interferon production, arrests Th1 cell infiltration and progression of
      insulitis, and inhibits diabetes development at nonhypercalcemic doses. Arrest of
      disease progression is accompanied by an enhanced frequency in the pancreatic
      lymph nodes of CD4(+)CD25(+) regulatory T-cells that are able to inhibit the T
      cell response to the pancreatic autoantigen insulinoma-associated protein 2 and
      to significantly delay disease transfer by pathogenic CD4(+)CD25(-) cells. Thus,
      a short treatment of adult NOD mice with an analog of 1,25-dihydroxyvitamin D(3)
      inhibits IL-12 production, blocks pancreatic infiltration of Th1 cells, enhances
      CD4(+)CD25(+) regulatory cells, and arrests the progression of type 1 diabetes,
      suggesting its possible application in the treatment of human autoimmune
      diabetes.

PMID- 11978633
TI  - Detection of GAD65-specific T-cells by major histocompatibility complex class II
      tetramers in type 1 diabetic patients and at-risk subjects.
AB  - Soluble HLA-DR401 or -DR404 tetramers containing a peptide corresponding to an
      immunodominant epitope from human GAD65 were used to analyze peripheral blood T
      cells of newly diagnosed type 1 diabetic patients and at-risk subjects.
      Peripheral blood mononuclear cells were expanded on antigen-presenting cells
      presenting GAD65 peptide and subsequently activated with specific plate-bound
      class II-peptide monomers. T-cell activation defined in flow cytometry by
      CD4(high) and/or CD25 markers were observed in all type 1 diabetic patients and
      some at-risk subjects, but not in normal control subjects. The activated T-cells
      stained positive with tetramers containing the GAD65 epitope 555-567. Tetramer
      positive cells were CD4(high) T-cells with high avidity for an immunodominant
      GAD65 T-cell epitope. Phenotyping of T-cells utilizing HLA class II tetramers
      provides a new tool to characterize the autoimmune response in type 1 diabetes.

PMID- 11978634
TI  - Insulin expression levels in the thymus modulate insulin-specific autoreactive T
      cell tolerance: the mechanism by which the IDDM2 locus may predispose to
      diabetes.
AB  - Type 1 diabetes results from autoimmune destruction of the insulin-producing
      pancreatic beta-cells. Evidence from our laboratory and others has suggested that
      the IDDM2 locus determines diabetes susceptibility by modulating levels of
      insulin expression in the thymus: the diabetes-protective class III alleles at a
      repeat polymorphism upstream of the insulin gene are associated with higher
      levels than the predisposing class I. To directly demonstrate the effect of
      thymic insulin expression levels on insulin-specific autoreactive T-cell
      selection, we have established a mouse model in which there is graded thymic
      insulin deficiency in linear correlation with insulin gene copy numbers, while
      pancreatic insulin remains unaltered. We showed that mice expressing low thymic
      insulin levels present detectable peripheral reactivity to insulin, whereas mice
      with normal levels show no significant response. We conclude that thymic insulin
      levels play a pivotal role in insulin-specific T-cell self-tolerance, a relation
      that provides an explanation for the mechanism by which the IDDM2 locus
      predisposes to or protects from diabetes.

PMID- 11978635
TI  - Fas/Fas ligand interactions play an essential role in the initiation of murine
      autoimmune diabetes.
AB  - Apoptosis via Fas/Fas ligand (FasL) interactions has been proposed to be a major
      T-cell-mediated effector mechanism in autoimmune diabetes. To elucidate the role
      of Fas/FasL interactions in NOD diabetes, the effects of neutralizing anti-FasL
      antibody on autoimmune responses were evaluated. Islet-specific CD8(+) and CD4(+)
      T-cells expressed FasL upon activation and mediated FasL-dependent cytotoxicity
      against Fas-expressing target cells in vitro, although their cytotoxicity against
      islet cells was not blocked by anti-FasL antibody. Moreover, administration of
      anti-FasL antibody failed to inhibit diabetes in vivo in the CD8(+) T-cell
      adoptive transfer model. On the other hand, blockade of Fas/FasL interactions
      significantly inhibited CD4(+) T-cell-dependent diabetes in adoptive transfer
      models. These results suggest a substantial contribution of Fas/FasL interactions
      to CD4(+), but not CD8(+), T-cell-mediated destruction of pancreatic beta-cells.
      When anti-FasL antibody was administered to NOD mice between 5 and 15 weeks of
      age, the onset of diabetes was slightly delayed but the incidence was not
      decreased. However, administration of anti-FasL antibody at 2-4 weeks of age
      completely prevented insulitis and diabetes. These results suggest that Fas/FasL
      interactions contribute to CD4(+) T-cell-mediated beta-cell destruction and play
      an essential role in the initiation of autoimmune NOD diabetes.

PMID- 11978636
TI  - Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces
      immature enterocytes to produce insulin.
AB  - Immature rat intestinal stem cells (IEC-6) given the ability to express the
      transcription factor, pancreatic duodenal homeobox 1 (Pdx-1), yielded YK cells.
      Although these cells produced multiple enteroendocrine hormones, they did not
      produce insulin. Exposure of YK cells to 2 nmol/l betacellulin yielded BYK cells
      that showed the presence of insulin expression in cytoplasm and that secreted
      insulin into culture media. By examining the mechanism of differentiation in BYK
      cells, we found that another transcription factor, islet factor 1 (Isl-1) was
      newly expressed with the disappearance of Pax-6 expression in those cells after
      exposure to betacellulin. These results indicated that combined expression of Pdx
      1 and Isl-1 in IEC-6 cells was required for the production of insulin. In fact,
      overexpression of both Pdx-1 and Isl-1 in IEC-6 cells (Isl-YK-12, -14, and -15
      cells) gave them the ability to express insulin without exposure to betacellulin.
      Furthermore, implantation of the Isl-YK-14 cells into diabetic rats reduced the
      animals' plasma glucose levels; glucose levels dropped from 19.4 to 16.9 mmol/l 1
      day after the injection of cells. As expected, the plasma insulin concentrations
      were 2.7 times higher in the diabetic rats injected with Isl-YK-14 cells compared
      to in controls. In summary, our results indicated that immature intestinal stem
      cells can differentiate into insulin-producing cells given the ability to express
      the transcription factors Pdx-1 and Isl-1.

PMID- 11978637
TI  - Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300
      on the GLUT2 gene promoter.
AB  - Mutations in the hepatocyte nuclear factor (HNF)-1alpha gene have been linked to
      subtype 3 of maturity-onset diabetes of the young (MODY), a disease characterized
      by a primary defect in insulin secretion. Here we show that the human GLUT2 gene
      is closely regulated by HNF-1alpha via sequences downstream of the
      transcriptional start site by interaction with transcriptional co-activator p300.
      The promoter region of the human GLUT2 gene was subcloned into luciferase
      expression plasmids that were transfected together with HNF-1alpha expression
      plasmid into a pancreatic beta-cell line, HIT-T15, to evaluate transcriptional
      activities. HNF-1alpha enhanced human GLUT2 promoter activity sixfold. Site
      direct mutagenesis and footprint analyses showed that the HNF-1alpha binding site
      (+200 to +218) is critical in human GLUT2 gene expression. Furthermore, mammalian
      two-hybrid and immunoprecipitation studies revealed the transactivation domain of
      HNF-1alpha (amino acids 391-540) to interact with both the NH(2)-terminal region
      (amino acids 180-662) and the COOH-terminal region (amino acids 1,818-2,079) of
      p300. These findings demonstrated that HNF-1alpha binds to the 5'-untranslated
      region of GLUT2 and that p300 acts as a transcriptional co-activator for HNF
      1alpha. In addition, these results provided new insight into the regulatory
      function of HNF-1alpha by suggesting a molecular basis for human GLUT2 gene
      expression.

PMID- 11978638
TI  - Insulin secretory function is impaired in isolated human islets carrying the
      Gly(972)-->Arg IRS-1 polymorphism.
AB  - Type 2 (non-insulin-dependent) diabetes results from decreased insulin action in
      peripheral target tissues (insulin resistance) and impaired pancreatic beta-cell
      function. These defects reflect both genetic components and environmental risk
      factors. Recently, the common Gly(972)-->Arg amino acid polymorphism of insulin
      receptor substrate 1 (Arg(972) IRS-1) has been associated with human type 2
      diabetes. In this study, we report on some functional and morphological
      properties of isolated human islets carrying the Arg(972) IRS-1 polymorphism.
      Insulin content was lower in variant than control islets (94 +/- 47 vs. 133 +/-
      56 microU/islet; P < 0.05). Stepwise glucose increase (1.7 to 16.7 mmol/l)
      significantly potentiated insulin secretion from control islets, but not Arg(972)
      IRS-1 islets, with the latter also showing a relatively lower response to
      glyburide and a significantly higher response to arginine. Proinsulin release
      mirrored insulin secretion, and the insulin-to-proinsulin ratio in response to
      arginine was significantly lower from Arg(972) IRS-1 islets than from control
      islets. Glucose utilization and oxidation did not differ in variant and wild-type
      islets at both low and high glucose levels. Electron microscopy showed that
      Arg(972) IRS-1 beta-cells had a severalfold greater number of immature secretory
      granules and a lower number of mature granules than control beta-cells. In
      conclusion, Arg(972) IRS-1 islets have reduced insulin content, impaired insulin
      secretion, and a lower amount of mature secretory granules. These alterations may
      account for the increased predisposition to type 2 diabetes in individuals
      carrying the Gly(972)-->Arg amino acid polymorphism of IRS-1.

PMID- 11978639
TI  - Modulation of L-type Ca(2+) channels by distinct domains within SNAP-25.
AB  - Cognate soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) proteins are now known to associate the secretory vesicle with both the
      target plasma membrane and Ca(2+) channels in order to mediate the sequence of
      events leading to exocytosis in neurons and neuroendocrine cells. Neuroendocrine
      cells, particularly insulin-secreting islet beta-cells, t-SNARE proteins, 25-kDa
      synaptosomal-associated protein (SNAP-25), and syntaxin 1A, independently inhibit
      the L-type Ca(2+) channel (L(Ca)). However, when both are present, they actually
      exhibit stimulatory actions on the L(Ca). This suggests that the positive
      regulation of the L(Ca) is conferred by a multi-SNARE protein complex. We
      hypothesized an alternate explanation, which is that each of these SNARE proteins
      possess distinct inhibitory and stimulatory domains that act on the L(Ca). These
      SNARE proteins were recently shown to bind the Lc(753-893) domain corresponding
      to the II and III intracellular loop of the alpha1C subunit of the L(Ca). In this
      study, using patch-clamp methods on primary pancreatic beta-cells and insulinoma
      HIT-T15 cells, we examined the functional interactions of the botulinum
      neurotoxin A (BoNT/A) cleavage products of SNAP-25, including NH(2)-terminal (1
      197 amino acids) and COOH-terminal (amino acid 198-206) domains, on the L(Ca),
      particularly at the Lc(753-893) domain. Intracellular application of SNAP-25(1
      206) in primary beta-cells decreased L(Ca) currents by approximately 15%. The
      reduction in L(Ca) currents was counteracted by coapplication of Lc(753-893).
      Overexpression or injection of wild-type SNAP-25 in HIT cells reduced L(Ca)
      currents by approximately 30%, and this inhibition was also blocked by the
      recombinant Lc(753-893) peptide. Expression of BoNT/A surprisingly caused an even
      greater reduction of L(Ca) currents (by 41%), suggesting that the BoNT/A cleavage
      products of SNAP-25 might possess distinct inhibitory and positive regulatory
      domains. Indeed, expression of SNAP-25(1-197) increased L(Ca) currents (by 19% at
      10 mV), and these effects were blocked by the Lc(753-893) peptide. In contrast,
      injection of SNAP-25(198-206) peptide into untransfected cells inhibited L(Ca)
      currents (by 47%), and more remarkably, these inhibitory effects dominated over
      the stimulatory effects of SNAP-25(1-197) overexpression (by 34%). Therefore, the
      SNARE protein SNAP-25 possesses distinct inhibitory and stimulatory domains that
      act on the L(Ca). The COOH-terminal 197-206 domain of SNAP-25, whose inhibitory
      actions dominate over the opposing stimulatory NH(2)-terminal domain, likely
      confers the inhibitory actions of SNAP-25 on the L(Ca). We postulate that the
      eventual accelerated proteolysis of SNAP-25 brought about by BoNT/A cleavage
      allows the relatively intact NH(2)-terminal SNAP-25 domain to assert its
      stimulatory action on the L(Ca) to increase Ca(2+) influx, and this could in part
      explain the observed weak or inconsistent inhibitory effects of BoNT/A on insulin
      secretion. The present study suggests that distinct domains within SNAP-25
      modulate L(C) subtype Ca(2+) channel activity in both primary beta-cells and
      insulinoma HIT-T15 cells.

PMID- 11978640
TI  - Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects
      on human pancreatic islets: evidence that beta-cell death is caspase mediated,
      partially dependent on ceramide pathway, and Bcl-2 regulated.
AB  - In an effort to better understand the phenomenon of lipotoxicity in human beta
      cells, we evaluated the effects of 48-h preculture with 1.0 or 2.0 mmol/l free
      fatty acid (FFA) (2:1 oleate to palmitate) on the function and survival of
      isolated human islets and investigated some of the possible mechanisms. Compared
      with control islets, triglyceride content was significantly increased and insulin
      content and glucose-stimulated insulin release were significantly reduced in
      islets precultured with increased FFA concentrations. These changes were
      accompanied by a significant reduction of glucose utilization and oxidation. By
      cell death detection techniques, it was observed that exposure to FFAs induced a
      significant increase of the amount of dead cells. Electron microscopy showed the
      involvement of beta-cells, with morphological appearance compatible with the
      presence of apoptotic phenomena. FFA-induced islet cell death was blocked by
      inhibition of upstream caspases and partially prevented by inhibiton of ceramide
      synthesis or serine protease activity, whereas inhibition of nitric oxide
      synthesis had no effect. RT-PCR studies revealed no major change of iNOS and Bax
      mRNA expression and a marked decrease of Bcl-2 mRNA expression in the islets
      cultured with FFA. Thus, prolonged exposure to FFAs has cytostatic and pro
      apoptotic effects on human pancreatic beta-cells. The cytostatic action is likely
      to be due to the FFA-induced reduction of intraislet glucose metabolism, and the
      proapoptotic effects are mostly caspase mediated, partially dependent on ceramide
      pathway, and possibly Bcl-2 regulated.

PMID- 11978641
TI  - Persistent improvement of type 2 diabetes in the Goto-Kakizaki rat model by
      expansion of the beta-cell mass during the prediabetic period with glucagon-like
      peptide-1 or exendin-4.
AB  - In the Goto-Kakizaki (GK) rat, a genetic model of type 2 diabetes, the neonatal
      beta-cell mass deficit is considered to be the primary defect leading to basal
      hyperglycemia, which is detectable for the first time 3 weeks after birth. We
      investigated in GK females the short- and the long-term effects of a treatment
      with glucagon-like peptide-1 (GLP-1) or its long-acting analog exendin-4 (Ex-4)
      during the first postnatal week (during the prediabetic period). GK rats were
      treated with daily injections of glucagon-like peptide-1 (400 microg x kg(-1) x
      day(-1)) or Ex-4 (3 microg x kg(-1) x day(-1)) from day 2 to day 6 after birth
      and were evaluated against Wistar and untreated GK rats. Under these conditions,
      on day 7 both treatments enhanced pancreatic insulin content and total beta-cell
      mass by stimulating beta-cell neogenesis and regeneration. Follow-up of
      biological characteristics from day 7 to adult age (2 months) showed that such a
      GLP-1 or Ex-4 treatment exerted long-term favorable influences on beta-cell mass
      and glycemic control at adult age. As compared to untreated GK rats, 2-month-old
      treated rats exhibited significantly decreased basal plasma glucose. Their
      glucose-stimulated insulin secretion, in vivo after intravenous glucose load or
      in vitro using isolated perfused pancreas, was slightly improved. This
      contributed at least partly to improve the in vivo plasma glucose disappearance
      rate, which was found to be increased in both treated GK groups compared to the
      untreated GK group. These findings in the GK model indicated, for the first time,
      that GLP-1 or Ex-4 treatment limited to the prediabetic period delays the
      installation and limits the severity of type 2 diabetes. Under these conditions,
      GLP-1 represents a unique tool because of its beta-cell replenishing effect in
      spontaneously diabetic rodents. It may prove to be an invaluable agent for the
      prevention of human type 2 diabetes.

PMID- 11978642
TI  - A potent and highly selective VPAC2 agonist enhances glucose-induced insulin
      release and glucose disposal: a potential therapy for type 2 diabetes.
AB  - Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal
      peptide (VIP) activate two shared receptors, VPAC1 and VPAC2. Activation of VPAC1
      has been implicated in elevating glucose output, whereas activation of VPAC2 may
      be involved in insulin secretion. A hypothesis that a VPAC2-selective agonist
      would enhance glucose disposal by stimulating insulin secretion without causing
      increased hepatic glucose production was tested using a novel selective agonist
      of VPAC2. This agonist, BAY 55-9837, was generated through site-directed
      mutagenesis based on sequence alignments of PACAP, VIP, and related analogs. The
      peptide bound to VPAC2 with a dissociation constant (K(d)) of 0.65 nmol/l and
      displayed >100-fold selectivity over VPAC1. BAY 55-9837 stimulated glucose
      dependent insulin secretion in isolated rat and human pancreatic islets,
      increased insulin synthesis in purified rat islets, and caused a dose-dependent
      increase in plasma insulin levels in fasted rats, with a half-maximal stimulatory
      concentration of 3 pmol/kg. Continuous intravenous or subcutaneous infusion of
      the peptide reduced the glucose area under the curve following an intraperitoneal
      glucose tolerance test. The peptide had effects on intestinal water retention and
      mean arterial blood pressure in rats, but only at much higher doses. BAY 55-9837
      may be a useful therapy for the treatment of type 2 diabetes.

PMID- 11978643
TI  - Chronic inhibition of circulating dipeptidyl peptidase IV by FE 999011 delays the
      occurrence of diabetes in male zucker diabetic fatty rats.
AB  - Acute suppression of dipeptidyl peptidase IV (DPP-IV) activity improves glucose
      tolerance in the Zucker fatty rat, a rodent model of impaired glucose tolerance,
      through stabilization of glucagon-like peptide (GLP)-1. This study describes the
      effects of a new and potent DPP-IV inhibitor, FE 999011, which is able to
      suppress plasma DPP-IV activity for 12 h after a single oral administration. In
      the Zucker fatty rat, FE 999011 dose-dependently attenuated glucose excursion
      during an oral glucose tolerance test and increased GLP-1 (7-36) release in
      response to intraduodenal glucose. Chronic treatment with FE 999011 (10 mg/kg,
      twice a day for 7 days) improved glucose tolerance, as suggested by a decrease in
      the insulin-to-glucose ratio. In the Zucker diabetic fatty (ZDF) rat, a rodent
      model of type 2 diabetes, chronic treatment with FE 999011 (10 mg/kg per os, once
      or twice a day) postponed the development of diabetes, with the twice-a-day
      treatment delaying the onset of hyperglycemia by 21 days. In addition, treatment
      with FE 999011 stabilized food and water intake to prediabetic levels and reduced
      hypertriglyceridemia while preventing the rise in circulating free fatty acids.
      At the end of treatment, basal plasma GLP-1 levels were increased, and pancreatic
      gene expression for GLP-1 receptor was significantly upregulated. This study
      demonstrates that DPP-IV inhibitors such as FE 999011 could be of clinical value
      to delay the progression from impaired glucose tolerance to type 2 diabetes.

PMID- 11978644
TI  - Unexpected sensitivity of nonobese diabetic mice with a disrupted poly(ADP
      Ribose) polymerase-1 gene to streptozotocin-induced and spontaneous diabetes.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that consumes NAD in
      response to DNA strand breaks. Its excessive activation seems particularly
      deleterious to pancreatic beta-cells, as exemplified by the complete resistance
      of PARP-1-deficient mice to the toxic diabetes induced by streptozotocin. Because
      of the possible implication of this enzyme in type 1 diabetes, many human trials
      using nicotinamide, an inhibitor of PARP-1, have been conducted either in
      patients recently diagnosed or in subjects highly predisposed to this disease. To
      analyze the role of this enzyme in murine type 1 diabetes, we introgressed a
      disrupted PARP-1 allele onto the autoimmune diabetes-prone nonobese diabetic
      (NOD) mouse strain. We showed that these mice were protected neither from
      spontaneous nor from cyclophosphamide-accelerated diabetes. Surprisingly they
      were also highly sensitive to the diabetes induced by a single high dose of
      streptozotocin, standing in sharp contrast with C57BL/6 mice that bear the same
      inactivated PARP-1 allele. Our results suggest that NOD mice are characterized
      not only by their immune dysfunction but also by a peculiarity of their islets
      leading to a PARP-1-independent mechanism of streptozotocin-induced beta-cell
      death.

PMID- 11978645
TI  - Increased efficiency of fatty acid uptake contributes to lipid accumulation in
      skeletal muscle of high fat-fed insulin-resistant rats.
AB  - In humans and animal models, increased lipid content of skeletal muscle is
      strongly associated with insulin resistance. However, it is unclear whether this
      accumulation is due to increased uptake or reduced utilization of fatty acids
      (FAs). We used (3)H-R-bromopalmitate tracer to assess the contribution of tissue
      specific changes in FA uptake to the lipid accumulation observed in tissues of
      insulin-resistant, high fat-fed rats (HFF) compared with control rats (CON) fed a
      standard diet. To study FA metabolism under different metabolic states, tracer
      was infused under basal conditions, during hyperinsulinemic-euglycemic clamp (low
      FA availability) or during the infusion of intralipid and heparin (high FA
      availability). FA clearance was significantly increased in the red gastrocnemius
      muscle of HFF under conditions of low (HFF = 10.4 +/- 1.1; CON = 7.4 +/- 0.5 ml x
      min(-1) x 100 g(-1); P < 0.05), basal (HFF = 8.3 +/- 1.4; CON = 4.5 +/- 0.7 ml x
      min(-1) x 100 g(-1); P < 0.01), and high (HFF = 7.0 +/- 0.8; CON = 4.3 +/- 0.5 ml
      x min(-1) x 100 g(-1); P < 0.05) FA levels. This indicates an adaptation by
      muscle for more efficient uptake of lipid. Associated with the enhanced
      efficiency of FA uptake, we observed increases in CD36/FA translocase mRNA
      expression (P < 0.01) and acyl-CoA synthetase activity (P < 0.02) in the same
      muscle. FA clearance into white adipose tissue was also increased in HFF when
      circulating FA were elevated, but there was little effect of the high-fat diet on
      hepatic FA uptake. In conclusion, insulin resistance induced by feeding rats a
      high-fat diet is associated with tissue-specific adaptations that enhance
      utilization of increased dietary lipid but could also contribute to the
      accumulation of intramuscular lipid with a detrimental effect on insulin action.

PMID- 11978646
TI  - Limited impact of vigorous exercise on defenses against hypoglycemia: relevance
      to hypoglycemia-associated autonomic failure.
AB  - Hypoglycemia-associated autonomic failure (HAAF)-reduced autonomic (including
      adrenomedullary epinephrine) and symptomatic responses to hypoglycemia caused by
      recent antecedent hypoglycemia-plays a key role in the pathogenesis of defective
      glucose counterregulation and hypoglycemia unawareness and thus iatrogenic
      hypoglycemia in type 1 diabetes. On the basis of the findings that cortisol
      infusion mimics and deficient or inhibited cortisol secretion minimizes this
      phenomenon, it has been suggested that the cortisol response to antecedent
      hypoglycemia mediates HAAF. We tested the hypothesis that any stimulus that
      releases cortisol, such as exercise, reduces autonomic and symptomatic responses
      to subsequent hypoglycemia. Thirteen healthy young adults (four women) were
      studied on three occasions in random sequence: 1) cycle exercise ( approximately
      70% peak oxygen consumption) from 0830 to 0930 h and from 1200 to 1300 h on day 1
      and hyperinsulinemic (2.0 mU x kg(-1) x min(-1)) stepped hypoglycemic (85, 75,
      65, 55, and 45 mg/dl) clamps on day 2, 2) rest on day 1 and identical
      hypoglycemic clamps on day 2, and 3) hyperinsulinemic-euglycemic clamps. Exercise
      raised plasma cortisol concentrations to 16.9 +/- 1.9 (0930 h) and 16.6 +/- 1.6
      microg/dl (1300 h) on day 1. Compared with rest on day 1, exercise on day 1 was
      associated with reduced epinephrine (P = 0.0113) responses-but not norepinephrine
      (P = 0.6270), neurogenic symptom (P = 0.6470), pancreatic polypeptide (P =
      0.0629), or glucagon (P = 0.0436, but higher) responses-to hypoglycemia on day 2.
      However, the effect was small. (The final day 2 hypoglycemia epinephrine values
      were 765 +/- 106 pg/ml after rest on day 1 and 550 +/- 94 pg/ml after exercise on
      day 1 compared with 30 +/- 6 pg/ml during euglycemia.) These data are consistent
      with the hypothesis that the cortisol response to hypoglycemia mediates in part
      the reduced epinephrine response to subsequent hypoglycemia, one key component of
      HAAF in type 1 diabetes. However, the small effect suggests that an additional
      factor or factors may well be involved. These data do not support the hypothesis
      that the cortisol response to hypoglycemia mediates the reduced neurogenic
      symptom response to subsequent hypoglycemia, another key component of HAAF in
      type 1 diabetes.

PMID- 11978647
TI  - Insulin and rosiglitazone regulation of lipolysis and lipogenesis in human
      adipose tissue in vitro.
AB  - Lipolysis is an important process determining fuel metabolism, and insulin
      regulates this process in adipose tissue. The aim of this study was to
      investigate the long-term effects of insulin, an insulin enhancer (rosiglitazone
      [RSG]), and insulin in combination with RSG on the regulation of lipolysis and
      lipogenesis in human abdominal subcutaneous fat. Lipolysis and lipogenesis were
      assessed by protein expression studies of hormone-sensitive lipase (HSL) (84 kDa)
      and lipoprotein lipase (LPL) (56 kDa), respectively. In addition, lipolytic rate
      was assessed by glycerol release assay and tumor necrosis factor (TNF)-alpha
      release measured by enzyme-linked immunosorbent assay (n = 12). In subcutaneous
      adipocytes, increasing insulin doses stimulated LPL expression, with maximal
      stimulation at 100 nmol/l insulin (control, 1.0 +/- 0.0 [mean +/- SE, protein
      expression relative to control]; 1 nmol/l insulin, 0.87 +/- 0.13; 100 nmol/l
      insulin, 1.68 +/- 0.19; P < 0.001). In contrast, insulin at the 100 nmol/l dose
      reduced the expression of HSL (100 nmol/l insulin, 0.49 +/- 0.05; P < 0.05),
      while no significant reduction was observed at other doses. Higher doses of
      insulin stimulated both HSL (1,000 nmol/l insulin, 1.4 +/- 0.07; P < 0.01) and
      LPL (control 1.00 +/- 0.0; 1,000 nmol/l insulin, 2.66 +/- 0.27; P < 0.01) protein
      expression. Cotreatment with RSG induced an increased dose response to insulin
      for LPL and HSL (P < 0.05); RSG alone also increased LPL and HSL expression (P <
      0.05). Insulin stimulated TNF-alpha secretion in a dose-dependent manner (P <
      0.01); the addition of RSG (10(-8) mol/l) reduced TNF-alpha secretion (P < 0.05).
      In summary, chronic treatment of human adipocytes with insulin stimulates
      lipolysis and LPL protein expression. The addition of RSG reduced the lipolytic
      rate and TNF-alpha secretion. The increase in lipolysis is not explained by
      changes in HSL expression. These data, therefore, may explain in part why
      hyperinsulinemia coexists with increased circulating nonesterified free fatty
      acids and increased adiposity in obese and/or type 2 diabetic patients.

PMID- 11978648
TI  - Gestational diabetes leads to the development of diabetes in adulthood in the
      rat.
AB  - We have developed a model of gestational diabetes in the rat to determine whether
      an altered metabolic intrauterine milieu is directly linked to the development of
      diabetes later in life. Uteroplacental insufficiency is induced in the pregnant
      rat on day 19 of gestation. Sham-operated animals serve as controls. Offspring
      are growth retarded at birth; however, they catch up by 5-7 weeks of age. At
      approximately 8 weeks of age, they are bred to normal males. During pregnancy,
      these animals develop progressive hyperglycemia and hyperinsulinemia accompanied
      by impaired glucose tolerance and insulin resistance. Offspring, designated as
      infants of a diabetic mother (IDMs), are heavier at birth and remain heavy
      throughout life. IDMs are insulin resistant very early in life, and glucose
      homeostasis is progressively impaired. Defects in insulin secretion are
      detectable as early as 5 weeks of age. By 26 weeks of age, IDMs are overtly
      diabetic. These data demonstrate that the altered metabolic milieu of the
      diabetic pregnancy causes permanent defects in glucose homeostasis in the
      offspring that lead to the development of diabetes later in life.

PMID- 11978649
TI  - Rosiglitazone, a peroxisome proliferator-activated receptor-gamma, inhibits the
      Jun NH(2)-terminal kinase/activating protein 1 pathway and protects the heart
      from ischemia/reperfusion injury.
AB  - This study was conducted to evaluate whether treatment of normal and diabetic rat
      hearts with rosiglitazone, a high-affinity ligand of the peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) used for the treatment of type 2 diabetes,
      improves postischemic functional recovery. The effects of acute rosiglitazone
      administration were investigated using working hearts isolated from normal rat or
      rats diabetic for 4 weeks after streptozotocin (STZ) injection. Hearts were
      subjected to 30 min of normothermic, zero-flow ischemia followed by 30-min
      reperfusion. Rosiglitazone (1 micromol/l) administered before ischemia had no
      effect on cardiac function during baseline perfusion, but it significantly
      improved aortic flow during reperfusion in both normal and diabetic hearts. In a
      chronic protocol in which rosiglitazone was given by daily gavage (10 micromol/kg
      body wt) immediately after STZ injection, rosiglitazone also prevented
      postischemic injury and significantly improved functional recovery. Using Western
      immunoblotting, it was demonstrated that the acute cardioprotective effect of
      rosiglitazone is associated with an inhibition of Jun NH(2)-terminal kinase
      phosphorylation in both normal and diabetic rat hearts. Furthermore,
      rosiglitazone also inhibited activating protein-1 DNA-binding activity. These
      data, demonstrating that rosiglitazone limits postischemic injury in isolated
      hearts, suggest an important function for PPAR-gamma in the heart.

PMID- 11978650
TI  - Direct evidence for insulin-induced capillary recruitment in skin of healthy
      subjects during physiological hyperinsulinemia.
AB  - It has been proposed that insulin-mediated changes in muscle perfusion modulate
      insulin-mediated glucose uptake. However, the putative effects of insulin on the
      microcirculation that permit such modulation have not been studied in humans. We
      examined the effects of systemic hyperinsulinemia on skin microvascular function
      in eight healthy nondiabetic subjects. In addition, the effects of locally
      administered insulin on skin blood flow were assessed in 10 healthy subjects.
      During a hyperinsulinemic clamp, we measured leg blood flow with venous occlusion
      plethysmography, skin capillary density with capillaroscopy, endothelium
      (in)dependent vasodilatation of skin microcirculation with iontophoresis of
      acetylcholine and sodium nitroprusside combined with laser Doppler fluxmetry, and
      skin vasomotion by Fourier analysis of microcirculatory blood flow. To exclude
      nonspecific changes in the hemodynamic variables, a time-volume control study was
      performed. Insulin iontophoresis was used to study the local effects of insulin
      on skin blood flow. Compared to the control study, systemic hyperinsulinemia
      caused an increase in leg blood flow (-0.54 +/- 0.93 vs. 1.97 +/- 1.1 ml. min(
      1). dl(-1); P < 0.01), an increase in the number of perfused capillaries in the
      resting state (-3.7 +/- 3.0 vs. 3.4 +/- 1.4 per mm(2); P < 0.001) and during
      postocclusive reactive hyperemia (-0.8 +/- 2.2 vs. 5.1 +/- 3.7 per mm(2); P <
      0.001), an augmentation of the vasodilatation caused by acetylcholine (722 +/-
      206 vs. 989 +/- 495%; P < 0.05) and sodium nitroprusside (618 +/- 159 vs. 788 +/-
      276%; P < 0.05), and a change in vasomotion by increasing the relative
      contribution of the 0.01- to 0.02-Hz and 0.4- to 1.6-Hz spectral components (P <
      0.05). Compared to the control substance, locally administered insulin caused a
      rapid increase ( approximately 13.5 min) in skin microcirculatory blood flow
      (34.4 +/- 42.5 vs. 82.8 +/- 85.7%; P < 0.05). In conclusion, systemic
      hyperinsulinemia in skin 1) induces recruitment of capillaries, 2) augments
      nitric oxide-mediated vasodilatation, and 3) influences vasomotion. In addition,
      locally administered insulin 4) induces a rapid increase in total skin blood
      flow, independent of systemic effects.

PMID- 11978651
TI  - The 807T allele in alpha2 integrin is protective against atherosclerotic arterial
      wall thickening and the occurrence of plaque in patients with type 2 diabetes.
AB  - Polymorphism of alpha2 integrin (C807T) is shown to be associated with an
      increased incidence of thrombotic cardiovascular events. However, it is not clear
      whether this polymorphism is associated with atherosclerotic arterial wall
      thickening. In this study, we examined the association of C807T polymorphism with
      arterial wall thickness in 265 control subjects and 272 patients with type 2
      diabetes. In all subjects, intima-media thickness of the right carotid artery in
      the 807TT group (0.649 +/- 0.028 mm [SE]) was significantly (P = 0.0228,
      Scheffe's F test) less than in the 807CC group (0.767 +/- 0.033). This effect of
      polymorphism is gene dose dependent (P = 0.0227, ANOVA). The similar association
      was also observed in patients with diabetes but not in control subjects. Multiple
      regression analysis in all subjects revealed that the T allele was inversely
      (beta = -0.095, P = 0.021) associated with intima-media thickness independent of
      age, HbA(1c), and HDL cholesterol. Finally, an inverse relation between the
      occurrence of carotid plaque and the T allele was observed in patients with
      diabetes with an adjusted odds ratio of 0.487 (P = 0.031) in multiple logistic
      regression analyses. These results suggest that the number of 807T alleles in
      alpha2 integrin is protective against atherosclerotic arterial wall thickening
      and the occurrence of plaque in patients with type 2 diabetes.

PMID- 11978652
TI  - The genetics of hypertension modifies the renal cell replication response induced
      by experimental diabetes.
AB  - To investigate whether the genetics of hypertension modifies renal cell responses
      in experimental diabetes, we studied the renal cell replication and its
      regulation by two cyclin-dependent kinase (Cdk) inhibitors, p27(Kip1) and
      p21(Cip1), in prehypertensive spontaneously hypertensive rats (SHR) and their
      genetically normotensive counterparts, Wistar Kyoto (WKY) rats, with and without
      streptozotocin-induced diabetes. In diabetic SHR, the number of proliferating
      glomerular (0.6 +/- 0.3 positive cells/50 glomeruli) and tubulointerstitial (2.8
      +/- 0.6 positive tubulointerstitial cells/50 grid fields) cells assessed by the
      bromodeoxyuridine technique was significantly (P = 0.0002) lower than in control
      SHR (13.2 +/- 1.7 and 48.6 +/- 9.7, respectively) and control (14.0 +/- 1.8 and
      63.9 +/- 10.6) and diabetic (14.3 +/- 3.5 and 66.4 +/- 11.5) WKY rats.
      Proliferating cell nuclear antigen, another marker of cell proliferation, was
      significantly reduced in replicating glomerular (P = 0.0002) and
      tubulointerstitial (P < 0.0001) cells in diabetic SHR. In freshly isolated
      glomeruli, the level of p27(Kip1) detected by Western blotting was significantly
      higher in diabetic SHR than in nondiabetic SHR (1.52 +/- 0.14 vs. 1.00 +/- 0.10%
      of control, P = 0.014). The expression of p21(Cip1) in isolated glomeruli did not
      differ among the groups of rats. In conclusion, the response of renal cell
      replication to diabetes differs markedly between prehypertensive SHR and their
      WKY control rats. The decreased glomerular cell proliferation in prehypertensive
      diabetic SHR is at least partly mediated by a higher expression of the Cdk
      inhibitor p27(Kip1).

PMID- 11978654
TI  - Associations of insulin levels with left ventricular structure and function in
      American Indians: the strong heart study.
AB  - We evaluated the association of insulin and echocardiographic left ventricular
      (LV) measurements in 1,388 (45% men) nondiabetic American Indian participants in
      the Strong Heart Study (SHS). Significant (all P < 0.05) relations were found in
      men and women between log(10) fasting insulin and LV mass (r = 0.24 and 0.26),
      left atrial diameter (r = 0.25 and 0.28), posterior wall thickness (r = 0.20 and
      0.26), septal thickness (r = 0.19 and 0.24), LV diameter (r = 0.17 and 0.16), and
      cardiac output (r = 0.20 and 0.24) and in women relative wall thickness (r =
      0.11) and peripheral resistance (r = -0.17). In regression analyses, adjusting
      for BMI, age, height, and systolic pressure, fasting insulin was independently
      correlated with cardiac output in men and relative wall thickness and septal
      thickness in women (all P < 0.05). The 97th percentiles of fasting insulin (25
      microU/ml for men, and 23 microU/ml for women) in 163 apparently normal (BMI <26;
      blood pressure <140/90; and absence of diabetes, valvular disease, LV wall motion
      abnormality, or antihypertensive treatment) SHS participants were used to
      separate normal from elevated fasting insulin levels. Adjusting for age, BMI, and
      height, men with elevated insulin levels had larger LV diameters (5.41 vs. 5.16
      cm; P = 0.05), higher cardiac output (5.5 vs. 4.9 l/min; P < 0.001), and lower
      peripheral resistance (1,487 vs. 1,666; P = 0.01), paralleling results of
      regression analyses. Positive relations between insulin and heart size in
      nondiabetic adults are largely due to associations with body size; after
      adjustments for covariates, fasting insulin levels are related to greater LV size
      and cardiac output in men and more concentric LV geometry in women.

PMID- 11978653
TI  - Advanced glycation end product precursors impair epidermal growth factor receptor
      signaling.
AB  - Formation of advanced glycation end products (AGEs) is considered a potential
      link between hyperglycemia and chronic diabetic complications, including
      disturbances in cell signaling. It was hypothesized that AGEs alter cell
      signaling by interfering with growth factor receptors. Therefore, we studied the
      effects of two AGE precursors, glyoxal (GO) and methylglyoxal (MGO), on the
      epidermal growth factor receptor (EGFR) signaling pathway in cultured cells. Both
      compounds prevented tyrosine autophosphorylation induced by epidermal growth
      factor (EGF) in a time- and dose-dependent manner as well as phospholipase
      Cgamma1 recruitment and subsequent activation of extracellular signal-regulated
      kinases. AGE precursors inhibit EGF-induced EGFR autophosphorylation and tyrosine
      kinase activity in cell membranes and in EGFR immunoprecipitates. In addition,
      AGE precursors strongly inhibited cellular phosphotyrosine phosphatase activities
      and residual EGFR dephosphorylation. AGE precursors induced the formation of EGFR
      cross-links, as shown by the cross-reactivity of modified EGFR with an anti
      N(epsilon)(carboxymethyl)lysine antibody, suggesting that altered EGFR signaling
      was related to carbonyl-amine reactions on EGFR. Aminoguanidine, an inhibitor of
      AGE formation, partially prevented the EGFR dysfunction induced by GO and MGO.
      These data introduce a novel mechanism for impaired cellular homeostasis in
      situations that lead to increased production of these reactive aldehydes, such as
      diabetes.

PMID- 11978655
TI  - MEDICA 16 inhibits hepatic acetyl-CoA carboxylase and reduces plasma
      triacylglycerol levels in insulin-resistant JCR: LA-cp rats.
AB  - Intracellular triacylglycerol (TG) content of liver and skeletal muscle
      contributes to insulin resistance, and a significant correlation exists between
      TG content and the development of insulin resistance. Because acetyl-CoA
      carboxylase (ACC) is the rate-limiting enzyme for liver fatty acid biosynthesis
      and a key regulator of muscle fatty acid oxidation, we examined whether ACC plays
      a role in the accumulation of intracellular TG. We also determined the potential
      role of 5'-AMP-activated protein kinase (AMPK) in this process, since it can
      phosphorylate and inhibit ACC activity in both liver and muscle. TG content, ACC,
      and AMPK were examined in the liver and skeletal muscle of insulin-resistant
      JCR:LA-cp rats during the time frame when insulin resistance develops. At 12
      weeks of age, there was a threefold elevation in liver TG content and a sevenfold
      elevation in skeletal muscle TG content. Hepatic ACC activity was significantly
      elevated in 12-week-old JCR:LA-cp rats compared with lean age-matched controls
      (8.75 +/- 0.53 vs. 3.30 +/- 0.18 nmol. min(-1). mg(-1), respectively), even
      though AMPK activity was also increased. The observed increase in hepatic ACC
      activity was accompanied by a 300% increase in ACC protein expression. There were
      no significant differences in ACC activity, ACC protein expression, or AMPK
      activity in the skeletal muscle of the 12-week JCR:LA-cp rats. Treatment of 12
      week JCR:LA-cp rats with MEDICA 16 (an ATP-citrate lyase inhibitor) resulted in a
      decrease in hepatic ACC and AMPK activities, but had no effect on skeletal muscle
      ACC and AMPK. Our data suggest that alterations in ACC or AMPK activity in muscle
      do not contribute to the development of insulin resistance. However, increased
      liver ACC activity in the JCR:LA-cp rat appears to contribute to the development
      of lipid abnormalities, although this increase does not appear to occur secondary
      to a decrease in AMPK activity.

PMID- 11978656
TI  - Mechanisms of amelioration of glucose-induced endothelial dysfunction following
      inhibition of protein kinase C in vivo.
AB  - Inhibition of protein kinase C (PKC) activity has been shown to improve the
      endothelial dysfunction associated with hyperglycemia and diabetes. The
      mechanisms by which inhibition of PKC activity ameliorates endothelial
      dysfunction in diabetes are not well understood. We investigated the relationship
      between PKC inhibition and leukocyte-endothelium interaction in the
      microcirculation of the rat mesentery exposed to 25 mmol/l D-glucose for 12 h. D
      Glucose significantly increased leukocyte rolling and adherence in mesenteric
      postcapillary venules. This proinflammatory action of D-glucose was inhibited by
      superfusion of the mesentery with 30 nmol/l bisindolylmaleimide-I, a potent,
      selective PKC inhibitor (P < 0.01 vs. glucose alone after 90 min of superfusion).
      Immunohistochemical localization of the cell adhesion molecules P-selectin and
      intercellular adhesion molecule (ICAM)-1 on the endothelial cell surface was
      increased by 25 mmol/l D-glucose (P < 0.001 vs. control tissue from rats injected
      with saline), which was significantly reduced by bisindolylmaleimide-I (P < 0.001
      vs. glucose alone). In addition, we studied adhesion of isolated neutrophils to
      rat superior mesenteric artery (SMA) vascular segments stimulated with 25 mmol/l
      D-glucose for 4 h in vitro. Pretreatment of the SMA vascular segments with either
      superoxide dismutase enzyme (100 units/ml) or bisindolylmaleimide-I (30 nmol/l)
      equally inhibited the increased neutrophil adherence to SMA endothelium in
      response to glucose. These data demonstrate that inhibition of PKC activity
      reduces leukocyte-endothelium interactions by suppressing surface expression of
      endothelial cell adhesion molecules in response to increased oxidative stress.
      These results provide a novel mechanism by which inhibition of PKC activity
      improves endothelial cell function in hyperglycemia and diabetes.

PMID- 11978657
TI  - Downregulation of connexin 43 expression by high glucose reduces gap junction
      activity in microvascular endothelial cells.
AB  - Impairment of retinal vascular homeostasis is associated with the development and
      progression of diabetic retinopathy involving gap junction intercellular
      communication (GJIC) activity. The principal gap junction protein of
      intercellular communication, connexin, was investigated to determine the effects
      of high glucose concentrations on the expression of endothelial-specific
      connexins (Cx37, Cx40, and Cx43), connexin phosphorylation pattern, and GJIC
      activity. Rat microvascular endothelial (RME) cells grown in high (30 mmol/l)
      glucose medium for 9 days had reduced Cx43 expression: Cx43 mRNA (68 +/- 13% of
      control; P = 0.019, n = 5) and protein (55.6 +/- 16% of control; P = 0.003, n =
      5) levels were reduced; however, Cx37 and Cx40 expression was not affected. Using
      alkaline phosphatase and Western blot analyses, we identified three forms of
      Cx43: a nonphosphorylated form (P0) and two phosphorylated forms (P1 and P2).
      Expression of all three forms was decreased in cells grown in high-glucose
      medium: PO, 73 +/- 15% of control (P = 0.04); P1, 57 +/- 16% of control (P =
      0.01); and P2, 42 +/- 22% of control (P = 0.006). Using immunofluorescence
      microscopy, we observed Cx43 localization at specific sites of contact (plaques)
      between adjacent cells. In cells grown in high-glucose medium, we observed
      reduced plaque counts (63 +/- 6% of control; P = 0.009) and decreased intensity
      of Cx43 immunofluorescence compared with cells grown in normal medium.
      Furthermore, using scrape load dye transfer (SLDT) technique, we found that these
      cells exhibited reduced GJIC activity (60% of control; P = 0.01, n = 5). The
      reduction in GJIC activity correlated with the decreased Cx43 protein levels (r =
      0.9). These results indicate that high glucose concentrations inhibited GJIC
      activity by reducing Cx43 synthesis in RME cells. Impaired intercellular
      communication may contribute to breakdown of homeostatic balance in diabetic
      microangiopathy.

PMID- 11978658
TI  - The early natural history of nephropathy in type 1 diabetes: I. Study design and
      baseline characteristics of the study participants.
AB  - This report describes the design and baseline demographic and clinical data in
      the study of the early natural history of diabetic nephropathy (DN) in type 1
      diabetes carried out by the International Diabetic Nephropathy Study Group. The
      study enrolled 243 patients ages 10-40 years (16.8 +/- 6.0, mean +/- SD) with
      type 1 diabetes for 2-20 years (8.0 +/- 4.2) at centers in the United States
      (Minneapolis), Canada (Montreal), and France (Paris). At baseline, all patients
      were normotensive, none had reduced glomerular filtration rate (GFR), and all but
      eight were normoalbuminuric (NA). All patients had baseline renal biopsies.
      During the study, patients will have multiple measurements of blood pressure
      (BP), renal function, albumin excretion rate (AER), glycemia, and other
      variables, with repeat renal biopsies planned at 5 years after baseline. The
      31.3% of the approached patients who agreed to participate were similar in age,
      diabetes duration, HbA(1c), AER, and sex to those refusing participation. Age,
      diabetes duration, HbA(1c), and AER were similar among the three centers, but
      systolic BP, GFR, renal plasma flow (RPF), and filtration fraction were lower in
      the Paris center. The 153 patients with hyperfiltration (GFR >130 ml x min(-1) x
      1.73 m(-2)) had greater RPF than those with normal GFR. The eight
      microalbuminuric patients tended to have longer duration of diabetes but were
      otherwise similar to the NA patients. The role of these and other variables in
      determining the development rate of the early lesions of DN over the 5 years
      between biopsies is the central issue under study.

PMID- 11978659
TI  - The early natural history of nephropathy in type 1 diabetes: II. Early renal
      structural changes in type 1 diabetes.
AB  - Renal structural abnormalities are known to precede the development of
      proteinuria, hypertension, and reduced renal function in patients with type 1
      diabetes. The determinants of these early structural abnormalities are, however,
      largely unknown. The International Diabetic Nephropathy Study (IDNS) has
      recruited 243 children and adults (aged 10-40 years) in Montreal, Minneapolis,
      and Paris to identify and quantify these determinants. All study subjects were
      normotensive and had normal-to-high glomerular filtration rates (GFRs) and
      urinary albumin excretion rates (AERs) <100 microg/min at study entry. Only 8 of
      243 had an AER > or =20 microg/min (microalbuminuria). Two renal biopsies are
      obtained at a 5-year intervals, with baseline and follow-up measures of renal
      function, blood pressure (BP), HbA(1c), plasma lipids, and AER. Herein, we
      examine the baseline renal biopsy morphometric findings in these subjects and in
      87 kidney donor control subjects and explore the associations between findings
      and clinical and demographic variables. The principal morphometric abnormalities
      were increased glomerular basement membrane (GBM) width and fractional volume of
      mesangium [Vv(Mes/glom)] and mesangial matrix [Vv(MM/glom)]. The frequency of
      these abnormalities increased with increasing duration of diabetes but was
      observed as early as 2-8 years after onset. Diastolic BP (DBP), but not HbA(1c),
      was directly associated with these abnormalities. Elevated GFR was associated
      with only a small increase in peripheral glomerular capillary basement membrane
      filtration surface density. Center differences were detected in renal structural,
      renal functional, and BP parameters, especially between the Paris and North
      American centers. GBM width, Vv(Mes/glom), and Vv(MM/glom) are significantly
      increased even within a few years of onset of type 1 diabetes. These changes are
      detectable in normoalbuminuric patients and are related to duration, BP, and
      study site. Changes in these and other morphometric measures over 5-year follow
      up should help clarify the roles of glycemia and other determinants of the rates
      of development of diabetic nephropathy lesions, as well as their relationships to
      early changes in BP, albumin excretion, and renal function.

PMID- 11978660
TI  - Accumulation of 8-hydroxy-2'-deoxyguanosine and mitochondrial DNA deletion in
      kidney of diabetic rats.
AB  - Oxidative stress may contribute to the pathogenesis of diabetic nephropathy.
      However, the detailed molecular mechanism remains uncertain. Here, we report
      oxidative mitochondrial DNA (mtDNA) damage and accumulation of mtDNA with a 4,834
      bp deletion in kidney of streptozotocin-induced diabetic rats. At 8 weeks after
      the onset of diabetes, levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is a
      marker of oxidative DNA damage, were significantly increased in mtDNA from kidney
      of diabetic rats but not in nuclear DNA, suggesting the predominant damage of
      mtDNA. Semiquantitative analysis using PCR showed that the frequency of 4,834-bp
      deleted mtDNA was markedly increased in kidney of diabetic rats at 8 weeks, but
      it did not change at 4 weeks. Intervention by insulin treatment starting at 8
      weeks rapidly normalized an increase in renal 8-OHdG levels of diabetic rats, but
      it did not reverse an increase in the frequency of deleted mtDNA. Our study
      demonstrated for the first time that oxidative mtDNA damage and subsequent mtDNA
      deletion may be accumulated in kidney of diabetic rats. This may be involved in
      the pathogenesis of diabetic nephropathy.

PMID- 11978661
TI  - C-reactive protein is an independent predictor of risk for the development of
      diabetes in the West of Scotland Coronary Prevention Study.
AB  - Accumulating evidence implicates inflammation as a potential pathway in the
      pathogenesis of type 2 diabetes. The objective of the present study was to assess
      the ability of C-reactive protein (CRP) to predict the development of diabetes in
      middle-aged men in the West of Scotland Coronary Prevention Study. Baseline
      plasma samples for CRP measurement were available for 5,245 men of whom 127 were
      classified as having a transition from normal glucose control to overt diabetes
      during the study, based on American Diabetes Association criteria. Baseline CRP
      was an important predictor of the development of diabetes in univariate analysis
      (hazard ratio [HR] for an increase of 1 SD = 1.55; 95% CI 1.32-1.82; P < 0.0001).
      In multivariate analysis, CRP remained a predictor of diabetes development (HR
      1.30; 95% CI 1.07-1.58; P = 0.0075) independent of other clinically employed
      predictors, including baseline BMI and fasting triglyceride and glucose
      concentrations. Moreover, there was a graded increase in risk across CRP
      quintiles throughout the study, evident at even 1 year of follow-up. The highest
      quintile (CRP >4.18 mg/l) was associated with a greater than threefold risk of
      developing diabetes (HR 3.07; 95% CI 1.33-7.10) in a multivariate analysis at 5
      years. Thus, CRP predicts the development of type 2 diabetes in middle-aged men
      independently of established risk factors. Because CRP, the most commonly used
      acute-phase protein in clinical practice, is very stable in serum, our
      observations have clinical potential in helping to better predict individuals
      destined to develop type 2 diabetes. They also add to the notion that low-grade
      inflammation is important in the pathogenesis of type 2 diabetes.

PMID- 11978662
TI  - Effect of the (C825T) Gbeta(3) polymorphism on adrenoceptor-mediated lipolysis in
      human fat cells.
AB  - A common Gbeta(3) gene polymorphism (C825T) influences G protein receptor
      mediated signal transduction. We investigated whether this polymorphism
      influences lipolysis in isolated subcutaneous fat cells from 114 healthy obese
      subjects. The Gbeta(3) protein content was markedly decreased in adipocytes of TT
      carriers, but the alternatively spliced short form of Gbeta(3) previously shown
      in platelets of 825T carriers was not detected. Fat cells of TT carriers showed a
      significant 10-fold decrease in the half-maximum effective concentration of
      agonists selective for lipolytic beta(1)- and beta(2)-adrenoceptors as well as
      for the antilipolytic alpha(2)A-adrenoceptor. In TT carriers, maximum beta
      adrenoceptor agonist-stimulated lipolysis was decreased, but the maximum
      antilipolytic effect of alpha(2)-adrenoceptors was less marked. Norepinephrine
      induced adipocyte lipolysis and circulating fasting levels of free fatty acids
      and glycerol were reduced by half in TT carriers. The polymorphism did not
      influence the adipocyte content of alpha(2)A-adrenoceptors, beta(2)
      adrenoceptors, Galpha(i), or Galpha(s). In conclusion, the C825T variant of
      Gbeta(3) influences lipolysis. Adipocytes of TT carriers have a lower Gbeta(3)
      protein content and a decreased function of native G(s)- as well as G(i)-coupled
      adrenoceptors, which reduces the lipolytic effect of catecholamines. These data
      differ from those obtained in other cell systems that have shown increased
      expression of an alternative spliced Gbeta(3) variant and enhanced G protein
      signaling in 825T carriers, indicating that the polymorphism has cell type
      specific effects that may be of importance for type 2 diabetes and other insulin
      resistant conditions.

PMID- 11978663
TI  - Contribution of known and unknown susceptibility genes to early-onset diabetes in
      scandinavia: evidence for heterogeneity.
AB  - In an attempt to identify novel susceptibility genes predisposing to early-onset
      diabetes (EOD), we performed a genome-wide scan using 433 markers in 222
      individuals (119 with diabetes) from 29 Scandinavian families with > or =2
      members with onset of diabetes < or =45 years. The highest nonparametric linkage
      (NPL) score, 2.7 (P < 0.01), was observed on chromosome 1p (D1S473/D1S438). Six
      other regions on chromosomes 3p, 7q, 11q, 18q, 20q, and 21q showed a nominal P
      value <0.05. Of the EOD subjects in these 29 families, 20% were GAD antibody
      positive and 68% displayed type 1 diabetes HLA risk alleles (DQB*02 or 0302).
      Mutations in maturity-onset diabetes of the young (MODY) 1-5 genes and the A3243G
      mitochondrial DNA mutation were detected by single-strand conformation
      polymorphism and direct sequencing. To increase homogeneity, we analyzed a
      subsample of five families with autosomal dominant inheritance of EOD (greater
      than or equal to two members with age at diagnosis < or =35 years). The highest
      NPL scores were found on chromosome 1p (D1S438-D1S1665; NPL 3.0; P < 0.01) and
      16q (D16S419; NPL 2.9; P < 0.01). After exclusion of three families with MODY1,
      MODY3, and mitochondrial mutations, the highest NPL scores were observed on
      chromosomes 1p (D1S438; NPL 2.6; P < 0.01), 3p (D3S1620; NPL 2.2; P < 0.03), 5q
      (D5S1465; NPL 2.1; P < 0.03), 7q (D7S820; NPL 2.0; P < 0.03), 18q (D18S535; NPL
      1.9; P < 0.04), 20q (D20S195; NPL 2.5; P < 0.02), and 21q (D21S1446; NPL 2.2; P <
      0.03). We conclude that considerable heterogeneity exists in Scandinavian
      subjects with EOD; 24% had MODY or maternally inherited diabetes and deafness,
      and approximately 60% were GAD antibody positive or had type 1 diabetes
      associated HLA genotypes. Our data also point at putative chromosomal regions,
      which could harbor novel genes that contribute to EOD.

PMID- 11978664
TI  - Polymorphisms in the oxygen-regulated protein 150 gene (ORP150) are associated
      with insulin resistance in Pima Indians.
AB  - The ORP150 gene that encodes the human oxygen-regulated protein (150 kDa) maps to
      chromosome 11q23, a region previously reported to be linked to type 2 diabetes
      and obesity in Pima Indians. This gene was also found to be differentially
      expressed in global gene expression studies comparing muscle mRNA from insulin
      resistant versus insulin-sensitive subjects. Therefore, ORP150 was analyzed as a
      candidate gene for susceptibility to diabetes. Twelve variants were identified,
      and three unique representative polymorphisms were genotyped in 1,338 Pima
      Indians. None of these polymorphisms were associated with diabetes, but two
      polymorphisms were significantly associated with measures of insulin resistance.
      These data indicate that ORP150 has a role in insulin action but does not have a
      major role in determining susceptibility to type 2 diabetes in Pima Indians.

PMID- 11978665
TI  - Haplotype combinations of calpain 10 gene polymorphisms associate with increased
      risk of impaired glucose tolerance and type 2 diabetes in South Indians.
AB  - Haplotype combination 112/121 and its intrinsic variants (UCSNP43, -19, and -63)
      identified within the calpain 10 gene are associated with increased risk of type
      2 diabetes in Mexican-Americans. We evaluated whether this haplotype combination
      and its constituent haplotypes and variants contribute to increased
      susceptibility to impaired fasting glucose (IFG)/impaired glucose tolerance (IGT)
      and type 2 diabetes in a South Indian population. Two study groups were used: 95
      families ascertained through a proband with type 2 diabetes and 468 subjects
      recruited as part of an urban survey (69.1% with normal glucose tolerance, 12.8%
      with IFG/IGT, and 18.2% with type 2 diabetes). The four-locus haplotype
      combination 1112/1121 (UCSNP44, -43, -19, and -63) in South Indians conferred
      both a 10.7-fold increased risk for IFG/IGT (P = 0.001) and a 5.78- to 6.52-fold
      increased risk for type 2 diabetes in the two study groups (families P = 0.025,
      urban survey P = 0.015). A combination of the 1112 haplotype with the 1221
      haplotype also appeared to increase risk for both IFG/IGT and type 2 diabetes.
      Contrary to what might be expected, quantitative trait analysis in the families
      found that transmission of the disease-related 1121 and 1112 haplotypes was
      associated with a reduced hip size and lower waist-to-hip ratio, respectively.
      This study supports the paradigm that specific haplotype combinations of calpain
      10 variants increase risk of both IFG/IGT and type 2 diabetes. However, the
      relative infrequency of the "at-risk" combinations in the South Indian population
      suggests that calpain 10 is not a common determinant of susceptibility to type 2
      diabetes.

PMID- 11978666
TI  - 5' flanking variants of resistin are associated with obesity.
AB  - Diabetes and obesity have long been known to be related. The recently
      characterized adipocyte hormone resistin (also called FIZZ3/ADSF) has been
      implicated as a molecular link between impaired glucose tolerance (IGT) and
      obesity in mice. A search for sequence variants at the human resistin locus
      identified nine single-nucleotide polymorphisms (SNPs) but no coding variants. An
      investigation into the association of these SNPs with diabetes and obesity
      revealed two 5' flanking variants (g.-537 and g.-420), in strong linkage
      disequilibrium, that are associated with BMI. In nondiabetic individuals from the
      Quebec City area and the Saguenay-Lac-St-Jean region of Quebec, the g.-537
      mutation (allelic frequency = 0.04) was significantly associated with an increase
      in BMI (P = 0.03 and P = 0.01, respectively). When the data from these two
      populations were combined and adjusted for age and sex, both the g.-537 (odds
      ratio [OR] 2.72, 95% CI 1.28-5.81) and the g.-420 variants (1.58, 1.06-2.35) were
      associated with an increased risk for a BMI > or =30 kg/m(2). In contrast, in
      case/control and family-based study populations from Scandinavia, we saw no
      effect on BMI with either of these promoter variants. No association was seen
      with diabetes in any of the population samples.

PMID- 11978667
TI  - A common polymorphism in the 5'-untranslated region of the VEGF gene is
      associated with diabetic retinopathy in type 2 diabetes.
AB  - Vascular endothelial growth factor (VEGF), a major mediator of vascular
      permeability and angiogenesis, may play a pivotal role in mediating the
      development and progression of diabetic retinopathy. In the present study, we
      examined the genetic variations of the VEGF gene to assess its possible relation
      to diabetic retinopathy in type 2 diabetic patients. Among seven common
      polymorphisms in the promoter region, 5'-untranslated region (UTR) and 3'UTR of
      the VEGF gene, genotype distribution of the C(-634)G polymorphism differed
      significantly (P = 0.011) between patients with (n = 150) and without (n = 118)
      retinopathy, and the C allele was significantly increased in patients with
      retinopathy compared with those without retinopathy (P = 0.0037). The odds ratio
      (OR) for the CC genotype of C(-634)G to the GG genotype was 3.20 (95% CI 1.45
      7.05, P = 0.0046). The -634C allele was significantly increased in patients with
      nonproliferative diabetic retinopathy (non-PDR) (P = 0.0026) and was
      insignificantly increased in patients with proliferative diabetic retinopathy
      (PDR) (P = 0.081) compared with patients without retinopathy, although
      frequencies of the allele did not differ significantly between the non-PDR and
      PDR groups. Logistic regression analysis revealed that the C(-634)G polymorphism
      was strongly associated with an increased risk of retinopathy (P = 0.0018).
      Furthermore, VEGF serum levels were significantly higher in healthy subjects with
      the CC genotype of the C(-634)G polymorphism than in those with the other
      genotypes. These data suggest that the C(-634)G polymorphism in the 5'UTR of the
      VEGF gene is a novel genetic risk factor for diabetic retinopathy.

PMID- 11978668
TI  - Positional candidate gene analysis of Lim domain homeobox gene (Isl-1) on
      chromosome 5q11-q13 in a French morbidly obese population suggests indication for
      association with type 2 diabetes.
AB  - The Lim domain homeobox gene (Isl-1) is a positional candidate gene for obesity
      that maps on chromosome 5q11-q13, a locus linked to BMI and leptin levels in
      French Caucasians. Isl-1 might be involved in body weight regulation and glucose
      homeostasis via the activation of proglucagon gene expression, which encodes for
      glucagon and glucagon-like peptides. By mutation screening of 72 obese subjects,
      we identified three single-nucleotide polymorphisms (SNPs) in the Isl1 gene. The
      allele frequencies in the morbidly obese group did not differ from that of the
      control group. In the obese group, the -47G allele was associated with a
      decreased risk of type 2 diabetes (odds ratio 0.41, P = 0.019). The AG bearers
      displayed a higher maximal BMI than the AA bearers in the whole obese group (P =
      0.026) as well as in the type 2 diabetic obese subgroup (P = 0.014). In obese
      families, this allele was not preferentially transmitted from heterozygous
      parents to their obese siblings, indicating that Isl-1 does not contribute to the
      linkage with obesity on 5cen-q. However, in French Caucasian morbidly obese
      subjects, the Isl1-47A-->G SNP may modulate the risk for type 2 diabetes and may
      increase body weight in diabetic morbidly obese subjects.

PMID- 11978669
TI  - Variation in three single nucleotide polymorphisms in the calpain-10 gene not
      associated with type 2 diabetes in a large Finnish cohort.
AB  - Variations in the calpain-10 gene have recently been reported to be associated
      with type 2 diabetes in a Mexican-American population. We typed three single
      nucleotide polymorphisms (SNPs) in the calpain-10 gene (SNPs 43, 56, and 63) to
      test for association between variation at these loci and type 2 diabetes and
      diabetes-related traits in 1,603 Finnish subjects: two samples of 526 (Finland
      U.S. Investigation of NIDDM Genetics [FUSION] 1) and 255 (FUSION 2) index case
      subjects with type 2 diabetes, 185 and 414 unaffected spouses and offspring of
      FUSION 1 index case subjects or their affected siblings, and 223 elderly normal
      glucose-tolerant control subjects. We found no significant differences in allele,
      genotype, haplotype, or haplogenotype frequencies between index case subjects
      with diabetes and the elderly and spouse control populations (all P > 0.087).
      Although variation in these three SNPs was associated with variation in some type
      2 diabetes-related traits within each of the case and control groups, no
      consistent pattern of the implicated variant or combination of variants was
      discerned. We conclude that variation in these three SNPs in the calpain-10 gene
      is unlikely to confer susceptibility to type 2 diabetes in this Finnish cohort.

PMID- 11978670
TI  - IL12B polymorphism and type 1 diabetes in the Italian population: a case-control
      study.
AB  - A polymorphism in the interleukin 12B gene was recently reported to be strongly
      associated with type 1 diabetes in 422 Australian and British families. We
      analyzed the same polymorphism in 470 Italian type 1 diabetic patients and 544
      matched control subjects and found no evidence of association with the disease.

PMID- 11978673
TI  - A controlled evaluation of staging dietary patterns to reduce the risk of
      diabetes in African-American women.
AB  - OBJECTIVE: This study evaluated the 3-month follow-up data of the Eat Well, Live
      Well Nutrition Program, a culturally specific, peer-led dietary change program
      designed to reduce the risk of type 2 diabetes in low-income African-American
      women. This peer-led program was delivered in the community and was tailored to
      the participants' stage of change for individual dietary patterns. We report the
      results of the 3-month intervention and the extent to which dietary changes and
      other key outcomes were maintained at a 3-month follow-up assessment. RESEARCH
      DESIGN AND METHODS: Using an experimental control group design, 294 overweight
      African-American women (ages 25-55 years), recruited in collaboration with a
      neighborhood organization, completed pre- and posttest and 3-month follow-up
      interviews of dietary behaviors, knowledge, attitudes, fat intake, and weight.
      RESULTS: Significant reductions were found in fat intake among women in the
      treatment condition when compared with women in the control group; these
      reductions were maintained at 3-month follow-up assessment. Likewise, significant
      changes in dietary patterns were reported after the study and were maintained,
      except for one dietary pattern (replacement). CONCLUSIONS: This model of health
      promotion, which individually tailors dietary patterns through staging and use of
      peer educators, has the potential for decreasing fat intake and increasing and
      maintaining specific low-fat dietary patterns among overweight African-American
      women at risk for diabetes.

PMID- 11978674
TI  - Evaluation of liver function in type 2 diabetic patients during clinical trials:
      evidence that rosiglitazone does not cause hepatic dysfunction.
AB  - OBJECTIVE: Troglitazone treatment has been associated with idiosyncratic hepatic
      reaction leading to hepatic failure and death in some patients. This raises
      questions regarding whether all thiazolidinediones or peroxisomal proliferator
      activated receptor-gamma (PPAR-gamma) agonists are hepatotoxic and whether data
      from clinical trials are adequate to detect a signal of potentially serious drug
      related hepatotoxicity. The purpose of this study was to assess whether the
      idiosyncratic liver toxicity reported with troglitazone is molecule-specific or a
      thiazolidinedione class effect, based on liver enzyme data collected
      prospectively during phase 2/3 clinical trials with rosiglitazone, a new, potent,
      and specific member of the thiazolidinedione class. RESEARCH DESIGN AND METHODS:
      This is an analysis of liver function in type 2 diabetic patients at baseline and
      serially in 13 double-blind, 2 open-label active-controlled, and 7 open-label
      extension studies of rosiglitazone treatment conducted in outpatient centers
      throughout North America and Europe. The study comprised > 6,000 patients aged 30
      80 years with type 2 diabetes. Patients underwent baseline liver function studies
      and were excluded from clinical trials if they had an alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), or alkaline phosphatase value 2.5 times
      greater than the upper limit of the reference range. The main outcome measures
      were liver enzyme levels, which were assessed at screening, at baseline, and
      every 4 weeks for the first 3 months of treatment and at 6- to 12-week intervals
      thereafter. Patients with at least one on-therapy ALT value >3 times the upper
      limit of the reference range were identified, and their case records examined in
      detail. RESULTS: At baseline, 5.6% of the patients with type 2 diabetes (mean
      HbA(1c) 8.5-9.0%) had serum ALT values between 1.0 and 2.5 times the upper limit
      of the reference range. On antidiabetic therapy, most of those patients (
      approximately 83%) had a decrease in ALT values, many into the normal range. The
      percentages of all patients with an on-therapy ALT value >3 times the upper limit
      of the reference range during double-blind and open-label treatment were as
      follows: rosiglitazone-treated 0.32%, placebo-treated 0.17%, and sulfonylurea-,
      metformin-, or insulin-treated 0.40%. The respective rates of ALT values >3 times
      the upper limit of the reference range per 100 person-years of exposure were
      0.29, 0.59, and 0.64. CONCLUSIONS: No evidence of hepatotoxic effects was
      observed in studies that involved 5,006 patients taking rosiglitazone as
      monotherapy or combination therapy for 5,508 person-years. This is in keeping
      with hepatic data from clinical trials of another member of the class,
      pioglitazone, and in contrast to the clear evidence of hepatotoxic effects
      observed during the troglitazone clinical trial program. These findings suggest
      that the idiosyncratic liver toxicity observed with troglitazone is unlikely to
      be a thiazolidinedione or a PPAR-gamma agonist class effect. Poorly controlled
      patients with type 2 diabetes may have moderate elevations of serum ALT that will
      decrease with improved glycemic control during treatment with rosiglitazone or
      other antihyperglycemic agents.

PMID- 11978676
TI  - The rising prevalence of diabetes and impaired glucose tolerance: the Australian
      Diabetes, Obesity and Lifestyle Study.
AB  - OBJECTIVE: To determine the population-based prevalence of diabetes and other
      categories of glucose intolerance (impaired glucose tolerance [IGT] and impaired
      fasting glucose [IFG]) in Australia and to compare the prevalence with previous
      Australian data. RESEARCH DESIGN AND METHODS: A national sample involving 11,247
      participants aged > or =25 years living in 42 randomly selected areas from the
      six states and the Northern Territory were examined in a cross-sectional survey
      using the 75-g oral glucose tolerance test to assess fasting and 2-h plasma
      glucose concentrations. The World Health Organization diagnostic criteria were
      used to determine the prevalence of abnormal glucose tolerance. RESULTS: The
      prevalence of diabetes in Australia was 8.0% in men and 6.8% in women, and an
      additional 17.4% of men and 15.4% of women had IGT or IFG. Even in the youngest
      age group (25-34 years), 5.7% of subjects had abnormal glucose tolerance. The
      overall diabetes prevalence in Australia was 7.4%, and an additional 16.4% had
      IGT or IFG. Diabetes prevalence has more than doubled since 1981, and this is
      only partially explained by changes in age profile and obesity. CONCLUSIONS:
      Australia has a rapidly rising prevalence of diabetes and other categories of
      abnormal glucose tolerance. The prevalence of abnormal glucose tolerance in
      Australia is one of the highest yet reported from a developed nation with a
      predominantly Europid background.

PMID- 11978675
TI  - Five-week, low-glycemic index diet decreases total fat mass and improves plasma
      lipid profile in moderately overweight nondiabetic men.
AB  - OBJECTIVE: To evaluate whether a 5-week low-glycemic index (LGI) diet versus a
      high-glycemic index (HGI) diet can modify glucose and lipid metabolism as well as
      total fat mass in nondiabetic men. RESEARCH DESIGN AND METHODS: In this study, 11
      healthy men were randomly allocated to 5 weeks of an LGI or HGI diet separated by
      a 5-week washout interval in a crossover design. RESULTS: The LGI diet resulted
      in lower postprandial plasma glucose and insulin profiles and areas under the
      curve (AUCs) than the HGI diet. A 5-week period of the LGI diet lowered plasma
      triacylglycerol excursion after lunch (AUC, P < 0.05 LGI vs. HGI). These
      modifications were associated with a decrease in the total fat mass by
      approximately 700 g (P < 0.05) and a tendency to increase lean body mass (P <
      0.07) without any change in body weight. This decrease in fat mass was
      accompanied by a decrease in leptin, lipoprotein lipase, and hormone-sensitive
      lipase RNAm quantities in the subcutaneous abdominal adipose tissue (P < 0.05).
      CONCLUSIONS: We concluded that 5 weeks of an LGI diet ameliorates some plasma
      lipid parameters, decreases total fat mass, and tends to increase lean body mass
      without changing body weight. These changes were accompanied by a decrease in the
      expression of some genes implicated in lipid metabolism. Such a diet could be of
      benefit to healthy, slightly overweight subjects and might play a role in the
      prevention of metabolic diseases and their cardiovascular complications.

PMID- 11978677
TI  - Hostility, race, and glucose metabolism in nondiabetic individuals.
AB  - OBJECTIVE: The present study was designed to determine whether hostility is
      differentially related to measures of glucose metabolism in African-Americans and
      Caucasians. RESEARCH DESIGN AND METHODS: The relationship of hostility, as
      measured by a subset of the Cook-Medley hostility scale (CMHOST) inventory items,
      to various parameters of glucose metabolism were examined in a young, healthy
      sample of male and female African-American and Caucasian volunteers. Fasting
      blood samples were collected during an inpatient admission, at which time the
      CMHOST was also administered. RESULTS: In the entire sample, the CMHOST was found
      to be significantly correlated with fasting glucose and insulin sensitivity, as
      measured by the homeostatic model assessment (HOMA). However, the relationship of
      hostility to these parameters of glucose metabolism was different in African
      American and Caucasian subjects. Hostility was significantly related to fasting
      glucose in African-Americans and to insulin sensitivity and fasting insulin in
      Caucasian subjects. The relationship of hostility to insulin sensitivity and
      fasting insulin was partially dependent on BMI in Caucasians, but the
      relationship of hostility to fasting glucose was unrelated to BMI in African
      Americans. CONCLUSIONS: Our data suggest that the relationship of hostility to
      measures of glucose metabolism is mediated differently in these two ethnic
      groups. Therefore, hostility seems to be part of a constellation of risk-related
      behaviors related to BMI in Caucasians but independently related to fasting
      glucose in African-Americans.

PMID- 11978678
TI  - The incidence of type 1 diabetes in the age group 0-39 years has not increased in
      Antwerp (Belgium) between 1989 and 2000: evidence for earlier disease
      manifestation.
AB  - OBJECTIVE: A worldwide increase in the incidence of childhood type 1 diabetes has
      been observed. Because in various countries the majority of new type 1 diabetic
      patients are diagnosed in adulthood, we investigated whether the rising incidence
      of this disorder in children reflects a global increase in the incidence of
      diabetes or a shift toward earlier clinical presentation. RESEARCH DESIGN AND
      METHODS: The incidence of type 1 diabetes presenting before age 40 years was
      prospectively measured in the Antwerp district over a 12-year period (1989-2000).
      The completeness of ascertainment was evaluated by the capture-recapture method.
      Trends in incidence during the study period were analyzed by Poisson regression.
      RESULTS: The incidence of type 1 diabetes diagnosed before age 40 years remained
      constant over the 12-year period, averaging 9.9 cases per 100,000 individuals per
      year. The incidence was similar in both sexes under age 15 years, but a marked
      male excess was noted for adult-onset disease, in particular after age 20 years,
      resulting in a male-to-female ratio of 0.9 under age 15 years vs. 1.6 thereafter
      (P = 0.001). During the 12-year observation period, there was a significant
      tendency toward increasing incidence under age 15 years at the expense of a
      decreasing incidence between ages 15 and 40 years (P = 0.025). The annual
      increase in incidence averaged 1.8% under age 15 years and 5.0% under age 5 years
      (P = 0.06). CONCLUSIONS: Our results indicate that in Belgium, the increasing
      incidence of childhood type 1 diabetes-especially for children under age 5 years
      is not attributable to a global increase in disease incidence, but rather to
      earlier clinical manifestation. The results suggest that an environmental factor
      may preferentially accelerate the subclinical disease process in young diabetes
      prone subjects.

PMID- 11978679
TI  - Gestational diabetes mellitus in women of single gravidity in Tianjin City,
      China.
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of gestational
      diabetes mellitus (GDM) and risk factors for the development of GDM in pregnant
      women in Tianjin, China, where the prevalence of GDM is still unknown. STUDY
      DESIGN AND METHODS: A total of 9,471 pregnant women living in the six urban
      districts of Tianjin, China, took part in the initial screening between December
      1998 and December 1999. The screening test consisted of a 50-g 1-h glucose test.
      Women with a reading > or =7.8 mmol/l at the initial screening were invited to
      undergo a 75-g 2-h oral glucose tolerance test (OGTT). GDM was confirmed using
      the World Health Organization's diagnostic criteria. RESULTS: At the initial
      screening test, 888 women had a glucose reading of > or =7.8 mmol/l. A total of
      701 (79%) women took a subsequent OGTT. Of these, 174 women were confirmed to
      have GDM (154 with impaired glucose tolerance [IGT] and 20 with diabetes). The
      prevalence of GDM was 2.31% (2.03% for IGT and 0.28% for diabetes), adjusting for
      serum glucose levels at the initial screening test. Independent predictors for
      GDM were maternal age, stature, prepregnancy BMI, weight gain in pregnancy before
      screening, diabetes in first-degree relatives, and habitual cigarette smoking
      during pregnancy. Women who smoked or had a short stature are more likely to
      develop GDM than their counterparts. CONCLUSIONS: The prevalence of GDM in
      pregnant women in the city of Tianjin, China, was 2.31%. Short stature and
      smoking in pregnancy were additional risk factors for GDM.

PMID- 11978680
TI  - Detection of symptoms by adolescents and young adults with type 1 diabetes during
      experimental induction of mild hypoglycemia: role of hormonal and psychological
      variables.
AB  - OBJECTIVE: To identify hormonal, psychological, and demographic predictors of
      symptom detection and accuracy of blood glucose estimation during mild
      hypoglycemia in adolescents and young adults with type 1 diabetes. RESEARCH
      DESIGN AND METHODS: During an insulin-glucose clamp study, 53 adolescents and 19
      young adults estimated blood glucose levels and reported symptoms at euglycemia
      and after 30 min of mild hypoglycemia (3.3 mmol/l). Epinephrine and pancreatic
      polypeptide were measured, and both change in anxiety level during hypoglycemia
      and baseline level of anxiety were measured with the Spielberger Anxiety
      Inventory. Elevated levels of anxiety during euglycemia were used as an indicator
      of the psychological trait "negative affectivity." Previous studies have
      suggested that individuals with higher negative affectivity are more internally
      focused and, therefore, more likely to report somatic and visceral changes.
      RESULTS: During mild hypoglycemia, 42% of the sample subjects reported an
      increase in autonomic symptoms; 29% reported an increase in neuroglycopenic
      symptoms, and 28% estimated blood glucose levels accurately (within 10% of
      actual). Hormonal excursions did not predict any outcome, but higher anxiety
      levels during the euglycemic baseline were associated with better detection of
      hypoglycemic symptoms and more accurate estimation of blood glucose values after
      controlling for change in anxiety level during hypoglycemia. CONCLUSIONS:
      Psychological factors such as elevated anxiety levels ("negative affectivity")
      can influence blood glucose estimation and symptom detection in adolescents and
      young adults and may explain why some individuals are more adept than others at
      reducing their risk of severe hypoglycemia after participation in a formal blood
      glucose awareness training program.

PMID- 11978681
TI  - Risk factors for development of incipient and overt diabetic nephropathy in type
      1 diabetic patients: a 10-year prospective observational study.
AB  - OBJECTIVE: To evaluate prospectively putative risk factors for development of
      microalbuminuria and macroalbuminuria in type 1 diabetes. RESEARCH DESIGN AND
      METHODS: Prospective observational study of a cohort of type 1 diabetic patients
      followed in the outpatient clinic at Steno Diabetes Center for < or =10 years
      (median 9 years). We followed 537 patients aged > or =18 years with type 1
      diabetes, with duration of diabetes > or =5 years, with normoalbuminuria (urinary
      albumin excretion rate < or =30 mg/24 h), and who were not taking
      antihypertensive medication. Risk factors for development of microalbuminuria and
      macroalbuminuria were evaluated. RESULTS: The mean progression of urinary albumin
      excretion rate was 7.6% (SE 0.8) per year. During follow-up, 134 patients (25%)
      progressed to persistent microalbuminuria or macroalbuminuria (>30 mg/24 h in two
      of three consecutive urine samples). Cox multiple regression analysis using
      baseline values of putative predictors of progression showed the following
      significant predictors of progression from normoalbuminuria to microalbuminuria
      or macroalbuminuria: baseline log urinary albumin excretion rate 2.63 (relative
      risk; 95% CI 1.65-4.19), HbA(1c) 1.13% (1.04-1.23), presence of any retinopathy
      1.90 (1.26-2.88), and smoking 1.61 (1.11-2.33). Sex, duration of diabetes,
      arterial blood pressure, serum creatinine, height, and social class were not risk
      factors. CONCLUSIONS: Our study suggests that several potentially modifiable risk
      factors predict the development of microalbuminuria and macroalbuminuria in type
      1 diabetic patients.

PMID- 11978682
TI  - Predisposition to atopic symptoms to inhaled antigens may protect from childhood
      type 1 diabetes.
AB  - OBJECTIVE: To assess the inverse association between type 1 diabetes and asthma
      to establish whether environmental and/or genetic factors predisposing to asthma
      or to atopic symptoms to inhaled antigens protect from diabetes. RESEACH DESIGN
      AND METHODS: Questionnaires were returned by 306 probands with childhood type 1
      diabetes, their 506 nonaffected siblings, and 406 age- and sex-matched unaffected
      population control subjects. The main outcome measures were self-reported
      physician-diagnosed asthma and atopic symptoms to animal dust and pollen.
      RESULTS: Risk of diabetes was inversely associated with asthma (odds ratio 0.49
      [95% CI 0.24-1.00]), allergy to animal dust (0.67 [0.45-0.99]), and to a lesser
      degree to pollen (0.74 [0.51-1.07]) when the probands were compared with the
      population control subjects. Among the children of the families of an affected
      proband, the risk of diabetes appeared to be inversely associated with asthma
      (0.54 [0.27-1.09]) but not with allergy to animal dust (0.99 [0.66-1.47]) nor
      allergy to pollen (0.88 [0.62-1.27]). CONCLUSIONS: The frequency of asthma and
      atopic symptoms to some inhaled antigens is decreased in individuals with
      childhood type 1 diabetes. Factors predisposing to atopic symptoms to inhaled
      antigens may protect from childhood type 1 diabetes.

PMID- 11978684
TI  - Immune responses to insulin aspart and biphasic insulin aspart in people with
      type 1 and type 2 diabetes.
AB  - OBJECTIVE: The antibody responses to a novel rapid-acting insulin analog, insulin
      aspart (IAsp), and their potential clinical correlates were studied with a
      specifically developed method in 2,420 people with diabetes treated for up to 1
      year with preprandial subcutaneous injections of IAsp. RESEARCH DESIGN AND
      METHODS: Circulating insulin antibodies were analyzed by radioimmunoassay with
      (125)I insulin or IAsp tracers and polyethylene glycol precipitation. Four
      multinational, open, parallel group studies were conducted in Europe and North
      America, with a total of 1,534 people with diabetes exposed to IAsp and 886
      people exposed to human insulin (HI) as meal-related insulin for 6-12 months.
      RESULTS: Insulin antibodies specific to HI or IAsp were absent in a majority of
      patients throughout the 6- to 12-month study periods. A majority of the patients
      (64-68%) had antibodies cross-reacting between HI and IAsp when entering the
      studies, with baseline levels (means +/- SD of percent bound/total) of 16.6 +/-
      16.3% in study 1 and 10.3 +/- 14.0% in study 4. In all four studies, cross
      reactive antibodies increased in patients exposed to IAsp, with a maximum at 3
      months, and thereafter there was a decline toward baseline levels at 9-12 months
      (levels at 3 and 12 months: 22.3 +/- 19.7 and 16.8 +/- 16.5% in study 1 and 21.5
      +/- 21.9 and 16.9 +/- 17.4% in study 4). Antibody levels showed similar changes
      in people with type 1 and type 2 diabetes, and there was no consistent
      relationship between antibody formation and glycemic control or between antibody
      formation and safety in terms of adverse events. CONCLUSIONS: Treatment with IAsp
      is associated with an increase in cross-reactive insulin antibodies, with a
      subsequent fall toward baseline values, without any indication of clinical
      relevance because no effect on efficacy or safety could be identified.

PMID- 11978683
TI  - Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week
      study period in type 2 diabetes.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment
      modality for type 2 diabetes. To circumvent the drawback of the short half-life
      of GLP-1, inhibitors of the GLP-1-degrading enzyme dipeptidyl peptidase IV (DPP
      IV) have been examined. Such inhibitors improve glucose tolerance in insulin
      resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2
      [(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP
      DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet
      controlled type 2 diabetes in a placebo-controlled double-blind multicenter
      study. RESEARCH DESIGN AND METHODS: A total of 93 patients (61 men and 32 women),
      aged 64 +/- 9 years (means +/- SD) and with BMI 27.3 +/- 2.7 kg/m(2), entered the
      study. Fasting blood glucose was 8.5 +/- 1.5 mmol/l, and HbA(1c) was 7.4 +/-
      0.7%. Before and after treatment with NVP DPP728 at 100 mg x 3 (n = 31) or 150 mg
      x 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with
      standardized meals (total 2,000 kcal). RESULTS: Compared with placebo, NVP DPP728
      at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose
      excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P <
      0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean
      24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023).
      Although not an efficacy parameter foreseen in the study protocol, HbA(1c) was
      reduced to 6.9 +/- 0.7% in the combined active treatment groups (P < 0.001).
      Laboratory safety and tolerability was good in all groups. CONCLUSIONS: We
      conclude that inhibition of DPP IV is a feasible approach to the treatment of
      type 2 diabetes in the early stage of the disease.

PMID- 11978685
TI  - Improved postprandial glycemic control with biphasic insulin aspart relative to
      biphasic insulin lispro and biphasic human insulin in patients with type 2
      diabetes.
AB  - OBJECTIVE: The rapid-acting insulin analogs aspart and lispro have now been
      developed in biphasic formulations. This trial compared the postprandial serum
      glucose control of biphasic insulin aspart 30 (BIAsp 30: 30% aspart, 70%
      protaminated aspart) with that of biphasic insulin lispro 25 (Mix25: 25% lispro,
      75% protaminated lispro) and biphasic human insulin 30 (BHI 30: 30% regular
      insulin, 70% NPH insulin) in insulin-treated subjects with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: This was an open-labeled, randomized, single-dose,
      three-way crossover trial of 61 insulin-treated subjects with type 2 diabetes who
      had no significant late diabetic complications. BIAsp 30 and Mix25 were injected
      subcutaneously immediately before a test meal, and BHI 30 was injected 15 min
      before a test meal. The primary target of analysis was serum glucose excursion 0
      5 h after a meal. RESULTS: The postprandial glycemic control with BIAsp 30, as
      assessed by the 5-h postmeal serum glucose excursion, was superior to that with
      both BHI 30 and Mix25 (16.6 +/- 4.5 vs. 20.1 +/- 4.9 and 18.9 +/- 6.1 mmol/l per
      hour, respectively; P < 0.001 and P < 0.05). For BIAsp 30 versus BHI 30, this was
      supported by a reduced maximum glucose concentration [C(max(SG))] (-5%; P < 0.05)
      occurring earlier (-13 min; P < 0.01). Furthermore, BIAsp 30 displayed a higher
      maximum serum insulin concentration (+101%; P < 0.001) occurring earlier (-55
      min; P < 0.001) compared with BHI 30. Compared with Mix25, there was a shorter
      time to C(max(SG)) (-11 min; P < 0.05) after treatment with BIAsp 30.
      CONCLUSIONS: This trial demonstrates that BIAsp 30 improves postprandial glycemic
      control compared with both Mix25 and BHI 30 in subjects with type 2 diabetes.

PMID- 11978686
TI  - Do sensor glucose levels accurately predict plasma glucose concentrations during
      hypoglycemia and hyperinsulinemia?
AB  - OBJECTIVE: The MiniMed Continuous Glucose Monitoring System (CGMS) measures
      subcutaneous interstitial glucose levels that are calibrated against three or
      more fingerstick glucose levels daily. The objective of the present study was to
      examine whether the relationship between plasma and interstitial fluid glucose is
      altered by changes in plasma glucose and insulin levels and how such alterations
      might influence CGMS performance. RESEARCH DESIGN AND METHODS: Arterialized
      plasma glucose, sensor glucose, and interstitial fluid glucose were measured by
      microdialysis in 11 healthy subjects during a 1.0 mU. kg(-1). min(-1) stepped
      euglycemic-hypoglycemic-hyperglycemic (plasma glucose approximately 5, 3.1, and
      8.6 mmol/l, respectively) insulin clamp that raised plasma insulin to
      approximately 360-390 pmol/l. RESULTS: When the CGMS was calibrated versus plasma
      glucose levels before insulin infusion, basal sensor and plasma glucose were
      similar (5.0 +/- 0.3 vs. 5.2 +/- 0.3 mmol/l, respectively); dialysate glucose was
      3.3 +/- 0.9 mmol/l. During the hyperinsulinemic-euglycemia study (plasma glucose
      4.9 +/- 0.3 mmol/l), dialysate glucose fell by 30-35%, accompanied by a
      significant reduction in sensor glucose (to 3.7 +/- 0.6 mmol/l; P < 0.001 vs.
      plasma). Subsequently, sensor levels remained lower than plasma values during
      mild hypoglycemia (2.5 +/- 0.6 vs. 3.1 +/- 0.3 mmol/l; P < 0.01) and during
      recovery from hypoglycemia (7.3 +/- 1.2 vs. 8.6 +/- 0.6; P < 0.01). However, when
      the CGMS was calibrated against plasma glucose levels before and during each step
      of the clamp, sensor glucose levels increased throughout the study and did not
      differ from plasma glucose values during hypoglycemia. CONCLUSIONS: Although
      hyperinsulinemia may contribute to modest discrepancies between plasma and sensor
      glucose levels, the CGMS is able to accurately track acute changes in plasma
      glucose when calibrated across a range of plasma glucose and insulin levels.

PMID- 11978687
TI  - UKPDS 59: hyperglycemia and other potentially modifiable risk factors for
      peripheral vascular disease in type 2 diabetes.
AB  - OBJECTIVE: To determine the role of hyperglycemia in prospective analyses of
      peripheral vascular disease (PVD) in type 2 diabetes, taking into account other
      potential risk factors. RESEARCH DESIGN AND METHODS: Potential risk factors for
      the development of PVD were examined in 3,834 of 5,102 individuals enrolled in
      the U.K. Prospective Diabetes Study (UKPDS) without PVD at diagnosis of diabetes,
      followed for 6 years, and for whom relevant data were available. PVD was defined
      as two of the following: ankle-arm blood pressure index < 0.8, absence of both
      dorsalis pedis and posterior tibial pulses to palpation in one or both legs, and
      intermittent claudication. Logistic regression was used to estimate the
      association between potential risk factors measured 3-4 months after diagnosis of
      diabetes and incident PVD. The prevalence of PVD at 3-year intervals to 18 years
      was determined. RESULTS: Hyperglycemia, assessed as HbA(1c), was associated with
      an increased risk for incident PVD, independent of other risk factors including
      age, increased systolic blood pressure, reduced HDL cholesterol, smoking, prior
      cardiovascular disease, peripheral sensory neuropathy, and retinopathy. Each 1%
      increase in HbA(1c) was associated with a 28% increased risk of PVD (95% CI 12
      46), and each 10-mmHg increase in systolic blood pressure with a 25% increase in
      risk (95% CI 10-43). CONCLUSIONS: Hyperglycemia, as well as smoking,
      dyslipidemia, and blood pressure are potentially modifiable risk factors for the
      development of PVD.

PMID- 11978688
TI  - Renal outcome in type 2 diabetic patients with or without coexisting nondiabetic
      nephropathies.
AB  - OBJECTIVE: To determine the risk factors for adverse renal outcome in type 2
      diabetic patients who underwent renal biopsy and were followed-up longitudinally.
      RESEARCH DESIGN AND METHODS: We examined 68 consecutive patients with type 2
      diabetes during the period of 1985-1999 who underwent renal biopsy for
      proteinuria > or =1 g/day, renal involvement (proteinuria or renal impairment) at
      the absence of retinopathy, renal involvement with duration of diabetes < 5
      years, or unexplained hematuria of glomerular origin. Their clinical features and
      underlying renal lesion were correlated with the renal outcome after longitudinal
      follow-up. Three groups of patients were defined based on their renal pathology:
      group I consisted of 24 patients (35%) with diabetic glomerulosclerosis (DGS)
      alone, group II consisted of 13 patients (19%) with nondiabetic nephropathy (NDN)
      superimposed on DGS, and group III consisted of 31 patients (46%) with NDN alone
      without evidence of DGS. RESULTS: After a mean follow-up of 123 months from the
      diagnosis of type 2 diabetes (74 months from the time of renal biopsy),
      univariate analysis showed that risk factors for reaching end-stage renal disease
      (requiring maintenance dialysis, or a serum creatinine [SCr] > or =700
      micromol/l) included proteinuria > or = 2g/day (P = 0.0087), SCr >120 micromol/l
      (P = 0.0005), presence of retinopathy (P < 0.00001) at the time of biopsy, and
      biopsy showing DGS (groups I and II) (P = 0.035). On multivariate analysis,
      retinopathy was the only independent variable correlated with end-stage renal
      failure. This study also showed that the association of hematuria or proteinuria
      with the absence of retinopathy constitutes the strongest indication for a
      nondiabetic lesion (positive predictive values of 94%). CONCLUSIONS: Patients
      with type 2 diabetes undergoing renal biopsy constitute a heterogeneous group by
      their clinical presentations and underlying pathology, but longitudinal studies
      on the renal outcome of these patients remain limited. Our study showed that
      renal biopsy is indicated in selective diabetic patients because of potentially
      treatable nephropathy and of a better prognosis than DGS.

PMID- 11978689
TI  - Impact of simultaneous pancreas and kidney transplantation on progression of
      coronary atherosclerosis in patients with end-stage renal failure due to type 1
      diabetes.
AB  - OBJECTIVE: Mortality in type 1 diabetic patients with end-stage renal failure is
      high and dominated by coronary atherosclerotic events. With regard to prognosis,
      simultaneous transplantation of pancreas and kidney (SPK) may be superior to
      kidney transplantation alone (KTA) in type 1 diabetic patients, because
      normalization of blood glucose levels may reduce progression of coronary
      atherosclerosis and because it is well known that progression of coronary
      atherosclerosis is one of the major factors that determines clinical prognosis.
      However, no data are available on progression of coronary atherosclerosis after
      SPK. RESEARCH DESIGN AND METHODS: We performed an observational angiographic
      study comparing progression of coronary atherosclerosis, analyzed with
      quantitative coronary angiography, in patients with (n = 26) and those without (n
      = 6) a functioning pancreas graft after SPK, to test the hypothesis that
      normalization of blood glucose levels by SPK may indeed reduce progression of
      coronary atherosclerosis in type 1 diabetic patients and thereby improve
      prognosis. RESULTS: Mean follow-up was 3.9 years. Average glucose control was
      significantly worse for the patients without a pancreas graft than for patients
      with a functioning pancreas graft: 11.3 (SD 3.5) vs. 5.9 mmol/l (SD 1.1) (P =
      0.03). Mean segment diameter loss (progression of diffuse coronary
      atherosclerosis) was 0.024 mm/year (SD 0.067) in patients with a functioning
      pancreas graft, compared with 0.044 mm/year (SD 0.038) in patients in whom the
      pancreas graft was lost. Minimum obstruction diameter loss (progression of focal
      coronary atherosclerosis) was 0.037 mm/year (SD 0.086) in patients with a
      functioning pancreas graft compared with 0.061 mm/year (SD 0.038) in patients in
      whom the pancreas graft was lost. Regression of atherosclerosis occurred in 38%
      of patients with a functioning pancreas graft compared with 0% of patients of
      whom the pancreas graft was lost (P = 0.035). CONCLUSIONS: Our study provides,
      for the first time, evidence that in patients who have undergone SPK, progression
      of coronary atherosclerosis in patients with a functioning pancreas graft is
      reduced compared with patients with pancreas graft failure. Our observation is an
      important part of the explanation for the observed improved mortality rates
      reported in type 1 diabetic patients with end-stage renal failure after SPK
      compared with KTA. In light of these findings described above, SPK must to be
      carefully considered for all diabetic transplant candidates.

PMID- 11978690
TI  - Delayed gastric emptying and gastric autoimmunity in type 1 diabetes.
AB  - OBJECTIVE: Delayed gastric emptying and/or gastrointestinal symptoms occur in 30
      50% of diabetic patients. Known contributing factors are autonomic neuropathy and
      acute hyperglycemia, but the role of gastric autoimmunity has never been
      investigated, although 15-20% of type 1 diabetic patients exhibit parietal cell
      antibodies (PCAs). We studied gastric motility in diabetes in relation to PCA
      status, autonomic nerve function, HbA(1c), thyroid-stimulating hormone (TSH),
      Helicobacter pylori (HP), acid production, and gastric histology. RESEARCH DESIGN
      AND METHODS: Gastric emptying of solids and liquids (measured by (13)C-octanoic
      acid and (13)C-glycine breath tests, respectively) was tested in euglycemic
      conditions in 42 type 1 diabetic patients (male/female: 29/13; 15 PCA+; mean age
      40 +/- 15 years; mean HbA(1c) 7.8 +/- 0.9%). Gastrointestinal symptoms, autonomic
      nerve function (Ewing tests), PCA status (indirect immunofluorescence), gastric
      histology, and acid secretion (pentagastrin) were assessed. RESULTS: Solid
      gastric emptying was delayed in 40% and liquid emptying in 36% of patients.
      Gastric motility did not correlate with symptoms. PCA status, gastric morphology,
      and acid secretion were similar in those with and without gastroparesis. HbA(1c)
      level (beta = 1.34, P = 0.011) was the only risk factor for delayed solid
      emptying in a logistic regression model testing HbA(1c), autonomic nerve
      function, PCA, HP status, age, sex, diabetes duration, and TSH. Half-emptying
      time for liquids correlated with TSH level (r = 0.83, P < 0.0001) and autonomic
      neuropathy score (r = -0.79, P = 0.001). CONCLUSIONS: We found that approximately
      50% of type 1 diabetic patients studied had delayed gastric emptying that did not
      correlate with symptoms. Gastric autoimmunity did not contribute to diabetic
      gastroparesis. Metabolic control was worse in patients with delayed solid
      emptying.

PMID- 11978691
TI  - Influence of cardiac autonomic neuropathy on heart rate dependence of ventricular
      repolarization in diabetic patients.
AB  - OBJECTIVE: Prolongation of the QT interval and increased QT dispersion are
      associated with a poor cardiac prognosis. The goal of this study was to assess
      the long-term influence of the autonomic nervous system on the heart rate
      dependence of ventricular repolarization in patients with diabetic autonomic
      neuropathy (DAN). RESEARCH DESIGN AND METHODS: We studied 27 subjects (mean age
      51.8 years) divided into three age- and sex-matched groups: nine control
      subjects, nine diabetic subjects with DAN (mostly at a mild stage; DAN+), and
      nine diabetic subjects without DAN (DAN-). DAN was assessed on heart rate
      variations during standard maneuvers (Valsalva, deep-breathing, and lying-to
      standing maneuvers). No subject had coronary artery disease or left ventricular
      dysfunction or hypertrophy, and no subject was taking any drugs known to prolong
      the QT interval. All subjects underwent electrocardiogram and 24-h Holter
      recordings for heart rate variations (time and frequency domain) and QT analysis
      (selective beat averaging QT/RR relation, nocturnal QT lengthening). RESULTS:
      Rate-corrected QT intervals (Bazett formula) did not differ significantly between
      the three groups. The diurnal and nocturnal levels of low frequency/high
      frequency, an index of sympathovagal balance, were significantly reduced in DAN+
      subjects. Using the selective beat-averaging technique, a day-night modulation of
      the QT/RR relation was evidenced in control and DAN- subjects. This long-term
      modulation was significantly different in DAN+ subjects, with a reversed day
      night pattern and an increased nocturnal QT rate dependence. CONCLUSIONS: In
      diabetic patients with mild parasympathetic denervation, QT heart rate dependence
      was found to be impaired, as determined by noninvasive assessment using Holter
      data. Analysis of ventricular repolarization could represent a sensitive index of
      the progression of neuropathy. The potential prognostic impact of a reversed day
      night pattern with steep nocturnal QT/RR relation still remains to be defined.

PMID- 11978692
TI  - The epidemiology of complications.

PMID- 11978693
TI  - What is the sensitivity and specificity of self-report for retinopathy screening?

PMID- 11978694
TI  - Association between twin pregnancy and hyperglycemia in a multiethnic community
      in New Zealand.

PMID- 11978695
TI  - A case of fulminant type 1 diabetes with elevated rheumatoid factor and the
      temporal presence of thyroid-stimulating hormone receptor antibody.

PMID- 11978696
TI  - Difference in the relation between urinary albumin excretion and carotid intima
      media thickness in nondiabetic and type 2 diabetic subjects.

PMID- 11978697
TI  - Reduced insulin sensitivity in Mexican-Americans from San Antonio with elevated
      incidence of type 2 diabetes compared with Mexicans from Mexico City.

PMID- 11978698
TI  - Correlation of serum leptin levels with insulin sensitivity in patients with
      chronic hepatitis-C infection.

PMID- 11978700
TI  - On methods and materials: response to Parretti et al.

PMID- 11978703
TI  - Diabetes care: interventions in the community.

PMID- 11978704
TI  - John B. O'Sullivan: a pioneer in the study of gestational diabetes.

PMID- 11978707
TI  - The need for palliative care to remain primary care focused.

PMID- 11978708
TI  - GPs' role in the prevention of suicide in schizophrenia.

PMID- 11978710
TI  - The effectiveness of local adaptation of nationally produced clinical practice
      guidelines.
AB  - BACKGROUND: Local adaptation is often reported in the literature to be an
      important strategy in achieving local ownership and relevance of guidelines in
      order to increase the likelihood of their uptake and implementation. However, the
      process is also potentially time-consuming and costly. OBJECTIVE: The aim of this
      study was to determine the impact of local adaptation of nationally produced
      clinical practice guidelines (CPGs) on the knowledge, attitude and reported
      practices of GPs. METHODS: Two Divisions of General Practice in Adelaide,
      Australia were selected and randomized to adapt a nationally produced CPG (on
      Stroke Prevention) by the National Health and Medical Research Council or use the
      original version. The order of the interventions was reversed for a second
      guideline (on management of Lower Urinary Tract Symptoms in Men). An identical
      multifaceted dissemination strategy was adopted for both sets of guidelines in
      the two divisions. Prior to the intervention, a random sample of 200 GPs from
      each Division was sent a postal survey about their knowledge, attitudes and
      reported practices. This was repeated 3 months after the dissemination phase.
      RESULTS: Sixty-one per cent (243/400) of the GPs responded to the initial survey
      and, of these, 76% (184/243) responded to the follow-up survey. Overall,
      awareness of both sets of guidelines was significantly increased. For stroke, 38%
      of respondents across both Divisions reported that their practice had changed as
      a result of the guidelines. For management of lower urinary tract symptoms in
      men, the corresponding proportion was 52%. Agreement with specific
      recommendations from both guidelines was also increased following their
      dissemination. However, these changes were independent of whether or not the
      guidelines had been locally adapted. The local adaptation process involved no
      substantive change in content and was estimated to cost AUD$5600 (per Division)
      independent of the costs of the dissemination process. CONCLUSIONS: Whilst this
      study found significant changes in knowledge, attitude and reported practice as a
      result of disseminating guidelines, it did not find any additional effect from
      the local adaptation process itself. This suggests that the emphasis and
      investment in promoting guideline implementation should be placed on multifaceted
      dissemination strategies rather than local adaptation per se.

PMID- 11978711
TI  - Open access endoscopy in an epidemiological situation of high prevalence of
      Helicobacter pylori infection: applicability of the guidelines of the European
      Society for Primary Care Gastroenterology.
AB  - BACKGROUND: Dyspepsia is a common syndrome and provides primary care physicians
      with a significant workload. To optimize the management of dyspepsia, several
      guidelines have been developed. OBJECTIVE: The aim of this study was to determine
      the incidence of upper gastrointestinal diseases and their relationship to
      Helicobacter pylori infection in dyspeptic patients referred for upper endoscopy
      by family physicians, as well as to assess the applicability of the guidelines of
      the European Society for Primary Care Gastroenterology (ESPCG). METHODS: A total
      of 168 unselected dyspeptic out-patients (mean age 38 years, range 18-75), 88
      male and 80 female, were included. Two biopsies from the antrum and two from the
      corpus were taken for histological assessment, and one from the antrum and one
      from the corpus were taken for culture. RESULTS: Half of the patients had
      clinically significant findings at endoscopy: peptic ulcer which occurred in 35%
      of the patients under the age of 30 years, in 45% of the patients in the age
      group 30-44 years and in 36% of the patients over 45 years of age. The prevalence
      of H. pylori infection in these age groups was 67, 87 and 89%, respectively.
      Duodenal ulcer was 12 times more common than gastric ulcer. CONCLUSIONS: The
      overall incidence of upper gastrointestinal disease, especially among young
      dyspeptic patients, was high compared with that observed in Western countries.
      The characteristics of dyspeptic patients, consulted in primary care, should be
      used for adaptation of the ESPCG guidelines to local needs.

PMID- 11978712
TI  - Demand, appropriateness and prescribing of 'lifestyle drugs': a consultation
      survey in general practice.
AB  - BACKGROUND: The simultaneous launch of orlistat and sildenafil in 1998 provoked
      much media attention, particularly around the role of lifestyle drugs and their
      potential costs if controls were not established. Fears were also expressed that
      primary care would be overwhelmed by demand, and little information was available
      about the attitude of GPs to their new role as prescribers of lifestlye drugs.
      Partly in response to these concerns, tight prescribing guidelines and licensed
      indications, for sildenafil and orlistat, respectively, were issued. OBJECTIVE:
      Our aim was to describe levels of demand for orlistat and sildenafil in general
      practice, whether this demand was translated into a prescription, adherence to
      prescribing guidelines/licensed indications and the GP perception of
      appropriateness of an NHS prescription for either of these drugs. METHOD: We
      carried out an observational study in primary care conducted over a 6-week period
      during 1999. Twenty-seven GPs were recruited, each from a different practice. All
      GP consultations were recorded for the study period and the GP completed a
      structured questionnaire each time sildenafil or orlistat were discussed in a
      consultation. RESULTS: Sildenafil was discussed in 0.5% (68/13 394) of
      consultations and orlistat in 0.3% (42/13 394). GPs thought that a corresponding
      NHS prescription would be highly appropriate in 57 and 74% of cases,
      respectively, although for both lifestyle drugs, nearly 20% of GPs thought such
      prescriptions were inappropriate. An NHS prescription was issued in 43% of
      consultations in which sildenafil had been discussed and 33% in which orlistat
      had been discussed. Five out of 29 NHS sildenafil prescriptions were issued to
      patients failing to fulfil the requirements of prescribing guidelines; similarly,
      one out of 14 orlistat prescriptions fell outside licensed indications. There
      were four examples of NHS prescriptions for sildenafil which were given even when
      the GP thought the drug to be inappropriate, whereas orlistat was never given
      when the GP thought it inappropriate. CONCLUSIONS: Levels of demand for the two
      lifestyle drugs, sildenafil and orlistat, were modest when compared with earlier
      media predictions. Neither was there evidence that GP was pitted against patient
      in their negotiation concerning a lifestyle drug NHS prescription since most GPs
      agreed with their patients that such a prescription was appropriate. Prescribing
      guidelines and licensed indications were generally adhered to, but the modest
      level of demand raises questions about expanding the guidelines for sildenafil.

PMID- 11978713
TI  - The impact of recurrent throat infection on children and their families.
AB  - BACKGROUND: Recurrent throat problems in children are common and have an impact
      on the family. The appropriateness of surgery will depend on both clinical and
      social factors. OBJECTIVES: The aim of this study was to assess the impact on the
      whole family when a child is suffering from recurrent throat problems, and
      investigate related parental attitudes. METHODS: A total of 1190 parents of
      children in northern England for whom tonsillectomy or adeno-tonsillectomy was a
      possible treatment option were sent a questionnaire covering social and clinical
      issues such as children's symptoms, the impact on family life and parental
      attitudes. RESULTS: The majority of children had experienced more than four
      episodes in the previous year, had their sleep affected and time off school. Most
      parents were worried and reported disruption to the family, including taking time
      off work and cross-infection. Parental disruption, worry and eagerness for
      surgery were significantly associated with the duration of episodes of throat
      problems and the number of episodes in the previous year, but not with duration
      of tonsillitis. Time off school, or parental time off work was significantly
      associated with parental worry and disruption, but not with eagerness for
      surgery. CONCLUSION: This work highlights the impact of recurrent throat problems
      and related parental attitudes, and will aid in striking a balance between
      clinical requirements and the needs and wishes of the family.

PMID- 11978714
TI  - Erectile dysfunction--the effect of sending a questionnaire to patients on
      consultations with their family doctor.
AB  - BACKGROUND: Erectile dysfunction (ED) is a common problem among male adults that
      generally has been ignored by family practitioners. OBJECTIVE: Our aim was to
      assess the effect of a mailed questionnaire about ED on the readiness of patients
      to raise the subject with their family doctor. METHODS: The study population
      included all men aged 40 years and over on the patient list of a family
      practitioner. A control group made up of males of similar ages was chosen in
      another family practice. The patient files were reviewed for ED. Anonymous
      questionnaires including questions about sexual dysfunction and satisfaction with
      sex life, as well as demographic and medical details, were sent to the study
      population. Patients who suffered from ED were invited to visit their family
      doctor. In the following 2 months, the study and control group populations'
      visits to the family practitioner were monitored for complaints of sexual
      dysfunction. RESULTS: In the 2 years prior to the study, 14/205 (6.8%) of the
      study population had complained to their family practitioner of ED in comparison
      with 6/205 (2.9%) in the control group (P = NS). In the 2 months following the
      sending of the questionnaire, 23 patients consulted their family practitioner
      with ED, 19 of whom had not discussed their problem with the family practitioner
      previously; only a further two patients went to discuss ED in the same period in
      the control group (P < 0.001). A total of 85/205 (41.5%) patients returned the
      questionnaire and 35/85 (42.5%) said they suffered from ED. Of 35 patients who
      reported ED, 15 had been for a consultation; only six of them consulted their
      family doctor. CONCLUSION: ED is reported infrequently to family doctors. Sending
      an anonymous questionnaire on the subject increases awareness of the problem and
      in turn increases the number of cases that can be treated.

PMID- 11978715
TI  - A short-term intervention in a multidisciplinary referral clinic for primary care
      frequent attenders: description of the model, patient characteristics and their
      use of medical resources.
AB  - BACKGROUND: Frequent attenders in primary care are a professional challenge for
      family physicians, and the medical costs of their care can be very high. Some of
      them suffer from somatization and are concerned solely with their physical
      complaints, although somatic complaints are the most common presentation of
      anxiety and depression. To assess and treat these patients comprehensively, a
      multidisciplinary clinic was created in the community. METHODS: This study
      describes the first 40 patients referred to the clinic. All patients completed a
      mental health screening questionnaire and a functional assessment of health. The
      utilization of medical resources was assessed by chart review for the year before
      and the year after the first encounter in the clinic. The intervention consisted
      of a comprehensive bio-psychosocial consultation where life history and medical
      symptoms were woven together into a new narrative. The intervention also included
      pharmacological treatment and short-term psychological interventions. RESULTS:
      The majority of referred patients were women and their average age was 52 years.
      Headache was the leading symptom, followed by fatigue. The mean number of
      reported symptoms for each individual patient was 10. Mental health problems were
      mainly somatization, depression and anxiety. The average yearly costs per person
      of US$4035 were reduced to US$1161 the year following referral. CONCLUSIONS: The
      integrated approach of the clinic satisfied at least three needs: of the patient,
      of the referring physician and of the health maintenance organization. The
      results of this uncontrolled pilot study suggest that this intervention helped to
      modify illness behaviour, decreasing the costs of medical investigations.

PMID- 11978716
TI  - The 'Medical Interview Satisfaction Scale' (MISS-21) adapted for British general
      practice.
AB  - BACKGROUND: The 29-item 'Medical Interview Satisfaction Scale' (MISS-29) was
      developed in the USA to assess patient satisfaction with individual doctor
      patient consultations. It has been used in studies from British general practice.
      However, there is limited evidence for its psychometric properties in this
      population. OBJECTIVES: The present study was designed to examine the validity,
      reliability and applicability of the MISS-29 in British general practice
      populations. METHODS: The study was divided into two phases. The first
      investigated the properties of the MISS-29 in a UK general practice population
      and resulted in a modified MISS (MISS-21). The second investigated the properties
      of the MISS-21 in a wider UK general practice population. In phase 1, 150
      patients over 16 years were recruited sequentially from patients attending a
      large group practice in suburban north London. Patients completed a questionnaire
      which collected demographic data and the MISS-29. In phase 2, 159 patients with a
      new problem were recruited from patients over 16 years consulting 18 GPs in north
      London, Essex and Suffolk. Patients completed a questionnaire while waiting to
      see the doctor; this collected demographic data and included six separate items,
      designed by the author, intended to measure patient satisfaction with previous
      consultations with the doctor. The patients completed the MISS-21 when they left
      the doctor's consulting room. RESULTS: The response rates for the phase 1 and
      phase 2 studies were 76.9 and 72.6%, respectively. Factor analysis, using
      principal component analysis with a varimax rotation, of the data collected in
      phase 1 resulted in a 21-item scale with the same four subscales as the original
      MISS-29. Correlations between subscales range from 0.46 to 0.65. Values of
      Cronbach's alpha between 0.67 and 0.92 suggest that the subscales are internally
      consistent under the conditions of the study. In phase 2, 92.1% completed all the
      items in the MISS-21 and there were no significant relationships between
      patients' demographic variables and the proportion of completed MISS-21
      questionnaires, nor were there any differences in the proportion of completed
      MISS-21 questionnaires between type of practice or between practices serving
      different geographic populations, suggesting that the items were acceptable to
      patients. There were highly significant positive correlations (0.21-0.63) between
      scores on the MISS-21 and all aspects of satisfaction with previous
      consultations, providing supportive evidence for the construct validity of the
      MISS-21. CONCLUSION: This study has demonstrated that the use in British general
      practice of the 29-item MISS developed in the USA should be treated with caution.
      However, a new 21-item version with the same four subscales as the 29-item MISS
      was developed which has satisfactory internal reliability. The correlations
      between subscales suggest that they represent fairly discrete but overlapping
      aspects of satisfaction. Evidence is produced suggesting that patients have less
      difficulty completing the MISS-21 and that it is applicable for assessing
      satisfaction with the consultation in different practice types and populations in
      the UK. Limited data supporting the construct validity of the MISS-21 are
      presented. While this study does not provide a full assessment of the MISS-21, we
      believe it provides evidence for its psychometric properties, which suggests that
      it is a valid and reliable instrument for the assessment of patient satisfaction
      with individual consultations in British general practice.

PMID- 11978717
TI  - The final version of the Patient Perspective Survey (PPS): a new tool to improve
      consultation outcome and patient participation in general practice patients with
      complex health problems. Doctors' and patients' evaluation and guidelines for
      clinical use.
AB  - BACKGROUND: The Patient Perspective Survey (PPS) is a new clinical communication
      tool designed to stimulate patient involvement in the management of complex
      health problems in general practice and to improve patient and doctor
      satisfaction with the consultation. The development of this final 38-item version
      of the PPS has been described elsewhere. OBJECTIVE: The aims of this article are
      to present recommendations for clinical use and how GPs and patients have
      evaluated this new tool. METHODS: The study material included 159 patients (78%
      females) with a mean age of 45 years, mainly presenting with longstanding
      musculoskeletal and psychosocial disorders, selected by 32 GPs. After the PPS
      based consultation, both doctor and patient were asked to fill in evaluation
      forms. RESULTS: In as many as 55-85% of the consultations' various aspects, it
      was perceived by the GPs that the use of the survey helped (to some extent, much
      or very much) in achieving improved clinical communication and a constructive
      consultation. The most important elements appeared to be stimulation of positive
      interaction/processes and obtaining new and relevant information. Similar results
      were found regarding patient evaluation. There was significantly more positive
      doctor evaluation if the doctor-patient relationship had lasted less than 1 year,
      and if the patient agreed to prepare a 'plan of action' for a follow-up
      consultation. Guidelines for clinical use are presented. CONCLUSION: We now
      regard the PPS to be completed for daily clinical use and believe that it has
      been shown to be a potent tool to improve consultation outcome in the large and
      challenging group of patients with complex health problems in general practice.

PMID- 11978718
TI  - Long-term mortality assessment using biological measures among elderly people.
      Ten-year follow-up of 597 healthy elderly subjects in Taiwan.
AB  - BACKGROUND: Identifying biological measures that are predictive of mortality for
      elderly people aged over 65 years has not been fully elucidated in oriental
      studies. OBJECTIVE: The associations between these biological measures and long
      term mortality were therefore investigated, and classifications for risk of death
      were developed among Taiwanese elderly people METHODS: Data used in this study
      were derived from a total of 597 apparently healthy subjects aged over 65 years
      identified from a nationwide survey that was conducted between 1989 and 1991 in
      Taiwan. Each participant received a physical examination and a wide range of
      biological measures. These 597 apparently healthy subjects were followed to 31
      December 1999 to determine the cause of death. The grouping technique using
      factor analysis was first used to aggregate similar characteristics of biological
      measures into reduced components. Risk of death for each subject was classified
      into four groups: good (A), fair (B), modest (C) and poor (D). Hazard ratios for
      groups B, C, D against A were calculated. RESULTS: The overall 10-year survival
      rate was 72% [95% confidence interval (CI) 68-76%]. The adjusted hazard ratios
      for all-cause death in high and mid-level categories of haematological components
      versus the lowest group were 0.51 (95% CI 0.33-0.80) and 0.56 (95% CI 0.37-0.85),
      respectively. Group D had a 6-fold risk of death as compared with group A
      (relative risk = 6.34, 95% CI 3.85-10.52). The corresponding figures were 2.48
      (95% CI 1.43-4.29) and 1.60 (95% CI 2.88-6.89) for groups B and C, respectively.
      CONCLUSIONS: The relationships of biological measures to long-term mortality were
      elucidated. Information on classification for risk of death may be helpful for
      elderly people to pay attention to their health status after receiving a health
      check-up.

PMID- 11978719
TI  - Group interviews in primary care research: advancing the state of the art or
      ritualized research?
AB  - BACKGROUND: Focus groups have become an important data gathering technique in
      primary care research. OBJECTIVES: This study provides an integrated review of
      recent articles that used focus groups as a data collection method to gather
      information from family physicians. METHODS: Medline was searched for articles
      that used focus groups with family physicians in a North American setting during
      the 1990s. Articles that met this criteria were critically evaluated to determine
      who participated, the number of groups conducted, setting, length, inclusion and
      exclusion criteria, sampling technique and whether the groups were used as part
      of a larger study. RESULTS: The twenty articles discussed herein revealed
      tremendous variation in how focus group research is conducted and reported.
      CONCLUSIONS: Focus group research is a popular form of qualitative research in
      primary care research. Journals reporting qualitative research should require
      that certain basic information be present, thereby advancing the state of the art
      and permitting readers to better evaluate these articles.

PMID- 11978720
TI  - Qualitative research and the problem of judgement: lessons from interviewing
      fellow professionals.
AB  - BACKGROUND: Qualitative research methods are recognized increasingly as valuable
      tools for primary care research, and add an extra dimension to quantitative work.
      OBJECTIVE: The aim of this study was to illustrate the benefits and problems
      attending the dual role of clinician/qualitative researcher. METHODS: As part of
      two studies employing semi-structured interviews of GPs in a North-West
      conurbation, about the topics of consultations on chronic low back pain and drug
      misuse in primary care, respondents' views on their interaction with a GP
      researcher were explored. RESULTS: Access to the GP by the interviewing GP was
      easier when the GP researcher was known to the respondent. Such prior knowledge,
      however, may then influence the content of the data and the manner in which the
      GP researcher is perceived. During the interview itself, where respondents
      recognized the researcher as a clinician, interviews were broader in scope and
      provided richer and more personal accounts of attitudes and behaviour in clinical
      practice. The GP was also identified as an expert and judge, not just of clinical
      decision making but also about moral judgements made by GPs in their work. This
      will impact on the data obtained at interview and must be taken into
      consideration when the data are interpreted and analysed. CONCLUSION: Qualitative
      research techniques increasingly are advocated as appropriate for research on and
      in general practice. The professional identity of the researcher plays an
      important part in constructing the kind of data obtained in such studies, and
      this must be made apparent in reporting and discussions of such qualitative work.

PMID- 11978721
TI  - Experiences by patients with asthma-like symptoms of a problem-based learning
      health education programme.
AB  - BACKGROUND: Eighteen patients with asthma-like symptoms but negative asthma
      tests, randomly selected, participated in a problem-based learning health
      education programme. The programme had a multidisciplinary approach and included
      exercises inspired by cognitive behavioural therapy. OBJECTIVE: The aim of this
      study was to describe how the patients experienced the programme. METHODS: After
      termination of the programme, semi-structured interviews with a phenomenographic
      approach were conducted with 15 of the participants. RESULTS: Two categories
      emerged, with three sub-categories each. In these, the informants described how
      they felt solidarity with the group, received confirmation from the other
      participants and had increased their self-confidence. They had started to look
      upon themselves and the disorder from a different perspective, they could
      describe the disorder in words and they had started to use new, conscious coping
      strategies. CONCLUSIONS: Patients with asthma-like symptoms benefit from taking
      part in a problem-based learning health education programme. It helps them to
      reflect upon themselves and the disorder and to use new strategies to cope with
      it.

PMID- 11978722
TI  - Pilot study of testicular cancer awareness and testicular self-examination in men
      attending two South London general practices.
AB  - BACKGROUND: Testicular cancer (TC) awareness and testicular self-examination
      (TSE) have never been evaluated adequately in UK general practice. TC has a 96%
      cure rate if detected early. OBJECTIVES: Our aim was to estimate awareness of TC
      and practice of TSE in a general practice population. METHOD: A cross-sectional
      questionnaire survey was carried out in 250 consecutive male attenders aged 18-50
      years in two general practices, one inner city, and one suburban. After obtaining
      informed consent, male patients in the waiting room were asked to complete a
      brief confidential questionnaire about TC and TSE. RESULTS: The response rate was
      81%. Mean age was 32 years (range 18-50). Seventy-five per cent of responders
      described themselves as white, 12% Asian, 6% black and 7% other ethnic groups.
      Ninety-one per cent were aware of TC but only 26% knew both the age group most
      affected (25-34 years) and that TC can be curable if detected early. Although 49%
      of responders had carried out TSE in the past year, only 22% were practising
      according to recommendations: feeling for lumps at least monthly. TSE was
      associated with age >35 years, white ethnicity, knowing someone with TC, having
      attended a Men's Health Clinic and having heard of the 'Everyman' TC awareness
      campaign. CONCLUSION: Although awareness of TC in this GP population was
      reasonable, less than half were practising TSE. Further public health campaigns
      may be needed.

PMID- 11978723
TI  - Evaluation of referrals from general practice to a neurological department.
AB  - BACKGROUND: The presence of neurological deficits as obtained from clinical
      examination increases the likelihood of detecting serious underlying brain
      disorders. OBJECTIVES: In this study, we assessed the frequency of reported
      clinical neurological examination in patients referred to neurology. METHODS: We
      consecutively evaluated referrals to a neurological centre during a 6-month
      period. RESULTS: From a total of 716 patients, 377 (51%) had an examination
      reported in the referral letter. Clinical examinations were reported more often
      in patients with musculo-skeletal disorders compared with others, P = 0.0001.
      Examination was less likely to be reported in those with a history of disturbed
      consciousness. CONCLUSION: By showing that only about half of the patients had an
      examination reported, the study demonstrates that the process of selecting those
      with a high priority for a secondary neurological service can be improved.

PMID- 11978725
TI  - Selections from current literature. Treatment issues in childhood obesity.

PMID- 11978724
TI  - Australian GPs are satisfied with their job: even more so in rural areas.
AB  - BACKGROUND: Australia has seen a constriction of the scope of practice and of
      professional prerogatives for GPs in the 1990s, which is said to have led to
      lower job satisfaction, particularly for rural GPs. OBJECTIVE: The aim of this
      study was to determine levels of job satisfaction and mental health in a rural
      and an urban sample of GPs, and to correlate population and practice
      characteristics with lower job satisfaction and morale. METHODS: A postal survey
      of GP members of two urban and four rural Divisions of General Practice in New
      South Wales was carried out using the Wall-Cook-Warr scale and the 12-item
      General Health Questionnaire (GHQ-12). The overall response rate was 74%.
      RESULTS: Both urban and rural Australian GPs were generally satisfied with their
      jobs; however, rural GPs had significantly higher job satisfaction scores. The
      highest levels of satisfaction were recorded for factors denoting autonomy. The
      lowest ranked factors were hours of work, income and government policy in general
      practice. GPs without psychological disturbance were significantly more satisfied
      with their work than those who were disturbed. Lower job satisfaction was
      significantly associated with urban GPs, GPs who worked full-time and those who
      used a language other than English during consultations. Poor mental health and
      working in an urban area were predictive of lower job satisfaction in men, and
      bulk-billing all patients (i.e. not charging patients a co-payment, but making a
      consolidated claim to the government funder Medicare) and working full-time were
      predictive of lower job satisfaction in women. CONCLUSIONS: Both urban and rural
      GPs derive a large measure of satisfaction from their job. In particular, rural
      GPs are satisfied, especially so with their autonomy. Poor mental health was the
      strongest predictor of lower job satisfaction. The high percentage of GPs with
      psychological disturbances raises the problem of their access to appropriate
      mental health services, in particular in rural areas.

PMID- 11978726
TI  - Shared decision making in hypertension.

PMID- 11978727
TI  - Cytoplasmic peptide:N-glycanase (PNGase) in eukaryotic cells: occurrence, primary
      structure, and potential functions.
AB  - A cytoplasmic peptide:N-glycanase has been implicated in the proteasomal
      degradation of newly synthesized misfolded glycoproteins exported from the
      endoplasmic reticulum. The gene encoding this enzyme (Png1p) has been identified
      in yeast. Based on sequence analysis, Png1p was classified as a member of the
      'transglutaminase-like superfamily' that contains a putative catalytic triad of
      amino acids (cysteine, histidine, and aspartic acid). More recent studies in
      yeast indicate that Png1p can bind to the 26S proteasome through its interaction
      with the DNA repair protein Rad23p. A mouse homologue of Png1p (mPng1p) bound not
      only to the Rad23 protein, but also to various proteins related to ubiquitin
      and/or the proteasome through an extended amino-terminal domain. This NH2
      terminus of mPng1p, which is not found in yeast, contains a PUB domain predicted
      to be involved in the ubiquitin-related pathway. This review will focus on the
      primary structure and potential functions of the cytoplasmic PNGases.

PMID- 11978728
TI  - Specificity mapping of human anti-T cell receptor monoclonal natural antibodies:
      defining the properties of epitope recognition promiscuity.
AB  - The classical concept of antibody binding is defined as an exclusive and high
      affinity interaction with one epitope. The emerging reality about antibody
      combing sites, however, is that some can bind unrelated determinants. The studies
      presented here define this quality as epitope recognition promiscuity by
      analyzing the capacity of monoclonal human autoantibodies to bind sets of
      overlapping peptides duplicating the complete structures of T cell receptor (TCR)
      alpha and beta chains and immunoglobulin lambda chain. We assessed the binding of
      these monoclonal antibodies (mAbs) to a set of homologous peptides corresponding
      to the CDR1 segments of human Vbeta gene products, a major epitope used in the
      selection of the antibodies. We present data on the binding characteristics of
      four human mAbs selected for the ability to bind TCR epitopes. These mAbs are IgM
      molecules with VH and VL sequences in germline configuration, but have diverse VH
      CDR3 regions. These studies aim to characterize the property of epitope
      promiscuity and show that the relationship between the binding site and its
      epitope is a complex interaction and unpredictable from antigen sequence alone.
      Our results support the conclusion that epitope recognition promiscuity is a
      genuine feature of antibody and TCR recognition.

PMID- 11978729
TI  - Role of creatine kinase in cardiac excitation-contraction coupling: studies in
      creatine kinase-deficient mice.
AB  - To understand the role of creatine kinase (CK) in cardiac excitation-contraction
      coupling, CK-deficient mice (CK-/-) were studied in vitro and in vivo. In skinned
      fibers, the kinetics of caffeine-induced release of Ca2+ was markedly slowed in
      CK-/- mice with a partial restoration when glycolytic substrates were added.
      These abnormalities were almost compensated for at the cellular level: the
      responses of Ca2+ transient and cell shortening to an increased pacing rate from
      1 Hz to 4 Hz were normal with a normal post-rest potentiation of shortening.
      However, the post-rest potentiation of the Ca2+ transient was absent and the
      cellular contractile response to isoprenaline was decreased in CK-/- mice. In
      vivo, echocardiographically determined cardiac function was normal at rest but
      the response to isoprenaline was blunted in CK-/- mice. Previously described
      compensatory pathways (glycolytic pathway and closer sarcoplasmic reticulum
      mitochondria interactions) allow a quasi-normal SR function in isolated cells and
      a normal basal in vivo ventricular function, but are not sufficient to cope with
      a large and rapid increase in energy demand produced by beta-adrenergic
      stimulation. This shows the specific role of CK in excitation-contraction
      coupling in cardiac muscle that cannot be compensated for by other pathways.

PMID- 11978730
TI  - Galactosylsphingosine (psychosine)-induced expression of cytokine-mediated
      inducible nitric oxide synthases via AP-1 and C/EBP: implications for Krabbe
      disease.
AB  - Globoid cell leukodystrophy (Krabbe disease) is characterized by the accumulation
      of a toxic metabolite, psychosine (galactosylsphingosine), which is a substrate
      for the deficient enzyme (galactocerebroside beta-galactosidase). This study
      underscores the possible role of psychosine in the effect of inducible nitric
      oxide synthase (iNOS) -derived NO in the pathophysiology of this demyelinating
      disease. For the first time, we provide evidence of the expression of iNOS in CNS
      of Krabbe patient and show that the iNOS-expressing cells in the CNS were
      astrocytes. Psychosine potentiated the LPS-induced production of proinflammatory
      cytokines (IL-1beta, IL-6, and TNF-alpha) in primary rat astrocytes and regulated
      the cytokine-mediated production of NO in C6 glioma and primary rat astrocyte.
      Psychosine induced cytokine-mediated nuclear translocation of AP-1 and C/EBP by
      potentiating the expression of Fra-1 and C/EBP-delta proteins. This suggests that
      psychosine maintained or sustained the cytokine-primed expression of iNOS by
      further potentiating the nuclear translocation of AP-1 and C/EBP without
      modulating the cytokine-mediated transcription activity of NF-kappaB. This study
      hypothesizes that accumulated psychosine leads to production of cytokines and
      iNOS expression. The ensuing excessive production of NO and ONOO- may play a role
      in pathogenesis of Krabbe disease.

PMID- 11978731
TI  - Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead
      to gait impairment, ectopic ossification, and osteoarthritis.
AB  - Small leucine-rich proteoglycans (SLRPs) regulate extracellular matrix
      organization, a process essential in development, tissue repair, and metastasis.
      In vivo interactions of biglycan and fibromodulin, two SLRPs highly expressed in
      tendons and bones, were investigated by generating biglycan/fibromodulin double
      deficient mice. Here we show that collagen fibrils in tendons from mice deficient
      in biglycan and/or fibromodulin are structurally and mechanically altered
      resulting in unstable joints. As a result, the mice develop successively and
      progressively 1) gait impairment, 2) ectopic tendon ossification, and 3) severe
      premature osteoarthritis. Forced use of the joints increases ectopic ossification
      and osteoarthritis in the double-deficient mice, further indicating that
      structurally weak tendons cause the phenotype. The study shows that mutations in
      SLRPs may predispose to osteoarthritis and offers a valuable and unique animal
      model for spontaneous osteoarthritis characterized by early onset and a rapid
      progression of the disease.

PMID- 11978732
TI  - SU6668 inhibits Flk-1/KDR and PDGFRbeta in vivo, resulting in rapid apoptosis of
      tumor vasculature and tumor regression in mice.
AB  - SU6668 is a small molecule inhibitor of the angiogenic receptor tyrosine kinases
      Flk-1/KDR, PDGFRbeta, and FGFR1. In mice, SU6668 treatment resulted in regression
      or growth arrest of all large established human tumor xenografts examined
      associated with loss of tumor cellularity. The events underlying loss of tumor
      cellularity were elucidated in detail in several tumor models. SU6668 treatment
      induced apoptosis in tumor microvessels within 6 h of the initiation of
      treatment. Dose-dependent decreases in tumor microvessel density were observed
      within 3 days of the first treatment. These changes were accompanied by decreased
      tumor cell proliferation and increased tumor cell apoptosis. Rapid increases in
      VEGF transcript levels were seen, consistent with the induction of tumor hypoxia.
      Using Western blot analyses, we determined that these in vivo antiangiogenic and
      proapoptotic effects of SU6668 occur at doses comparable to those required to
      inhibit Flk-1/KDR and PDGFRbeta phosphorylation in tumors. Potent, dose-dependent
      inhibition of Flk-1/KDR activity in vivo was independently demonstrated using
      vascular permeability as a readout. These data demonstrate that SU6668-induced
      inhibition of angiogenic receptor tyrosine kinase activity in vivo is associated
      with rapid vessel killing in tumors, leading to broad and potent antitumor
      effects.

PMID- 11978733
TI  - Thymosin beta4 is released from human blood platelets and attached by factor
      XIIIa (transglutaminase) to fibrin and collagen.
AB  - The beta-thymosins constitute a family of highly conserved and extremely water
      soluble 5 kDa polypeptides. Thymosin beta4 is the most abundant member; it is
      expressed in most cell types and is regarded as the main intracellular G-actin
      sequestering peptide. There is increasing evidence for extracellular functions of
      thymosin beta4. For example, thymosin beta4 increases the rate of attachment and
      spreading of endothelial cells on matrix components and stimulates the migration
      of human umbilical vein endothelial cells. Here we show that thymosin beta4 can
      be cross-linked to proteins such as fibrin and collagen by tissue
      transglutaminase. Thymosin beta4 is not cross-linked to many other proteins and
      its cross-linking to fibrin is competed by another family member, thymosin
      beta10. After activation of human platelets with thrombin, thymosin beta4 is
      released and cross-linked to fibrin in a time- and calcium-dependent manner. We
      suggest that thymosin beta4 cross-linking is mediated by factor XIIIa, a
      transglutaminase that is coreleased from stimulated platelets. This provides a
      mechanism to increase the local concentration of thymosin beta4 near sites of
      clots and tissue damage, where it may contribute to wound healing, angiogenesis
      and inflammatory responses.

PMID- 11978734
TI  - A pivotal role for cADPR-mediated Ca2+ signaling: regulation of endothelin
      induced contraction in peritubular smooth muscle cells.
AB  - cADPR, a potent calcium-mobilizing intracellular messenger synthesized by ADP
      ribosyl cyclases regulates openings of ryanodine receptors (RyR). Here we report
      that in the rat testis, a functional cADPR Ca2+ release system is essential for
      the contractile response of peritubular smooth muscle cells (PSMC) to endothelin
      (ET). We previously showed that this potent smooth muscle agonist elicits
      intracellular Ca2+ release in PSMC and seminiferous tubule contraction via
      activation of ETA and ETB receptors. ETB-R induces the mobilization of a
      thapsigargin-sensitive but IP3-independent intracellular Ca2+ pool. Stimulation
      of permeabilized PSMC with cADPR was found to elicit large Ca2+ releases blocked
      by either a selective antagonist of cADPR or a RyR blocker, but not by heparin.
      Western blotting and confocal fluorescence microscopy indicated the specific
      expression of type 2 RyR in perinuclear localization. ET was found to stimulate
      the activity of ADP-ribosyl cyclase. Microinjection of the selective cADPR
      antagonist 8NH2-cADPR completely abolished subsequent stimulation of Ca2+
      signaling via ETA and ETB receptors. cADPR therefore appears to have an
      obligatory role for ETA-R and ETB-R-mediated calcium signaling in PSMC. However,
      ETB-R seem to be coupled exclusively to cADPR whereas ETA-R activation may be
      linked to IP3 and cADPR signaling pathways.

PMID- 11978735
TI  - Dephosphorylation of endothelial nitric oxide synthase contributes to the anti
      angiogenic effects of endostatin.
AB  - Endostatin is an anti-angiogenic factor that inhibits endothelial cell (EC)
      migration and induces EC apoptosis. Because nitric oxide (NO) plays a key role in
      vascular endothelial growth factor (VEGF)-induced angiogenesis, we hypothesized
      that endostatin interferes with the activation of the endothelial NO synthase
      (eNOS). Human recombinant endostatin significantly reduced VEGF-induced NO
      release, which suggests that endostatin inhibits eNOS activation. Because the
      activation of eNOS by VEGF is associated with the Akt-dependent phosphorylation
      of eNOS at Ser1177, we investigated whether endostatin interferes with
      phosphorylation of eNOS. Endostatin reduced VEGF-induced phosphorylation of eNOS
      at Ser1177, whereas Akt phosphorylation was not affected. Coinciding with the
      inhibition of eNOS phosphorylation, endostatin completely blocked VEGF-induced EC
      migration. The NO-donor SNAP reversed the inhibitory effect of endostatin on EC
      migration. In addition, endostatin significantly inhibited VEGF-induced tube
      formation, whereas endostatin did not affect tube formation induced by NO.
      Finally, a non-dephosphorylatable constitutive active eNOS construct (S1177D),
      but not constitutive active Akt, abolished the inhibitory effect of endostatin on
      EC migration. Endostatin activated PP2A, which is known to directly
      dephosphorylate eNOS at Ser1177. Inhibition of PP2A prevented the inhibitory
      effect of endostatin. Thus, endostatin inhibits VEGF-induced EC migration and
      angiogenesis upstream of NO-synthesis via dephosphorylation of eNOS at Ser1177.

PMID- 11978736
TI  - A ubiquitin-proteasome system is responsible for the protection of yeast and
      human cells against methylmercury.
AB  - The mechanism responsible for the toxic effects of methylmercury (MeHg), an
      important environmental pollutant, is poorly understood. We have identified a
      gene, CDC34, that confers resistance to MeHg in Saccharomyces cerevisiae by
      screening a yeast genomic DNA library. CDC34 encodes a ubiquitin-conjugating
      enzyme, Cdc34, which is involved in ubiquitin-dependent proteolysis.
      Overexpression of Cdc34 results in significant resistance to MeHg both in yeast
      and human cells, and it increases the cellular level of ubiquitinated proteins.
      The ubiquitin-conjugating activity of Cdc34 is essential for the Cdc34-mediated
      resistance to MeHg, and the protective effect of the overexpression of Cdc34 is
      depressed by inhibition of proteasome activity. Our results support the
      hypothesis that MeHg induces the cellular accumulation of a certain protein(s)
      that causes cell damage and that this protein(s) is degraded after its
      ubiquitination in proteasomes.

PMID- 11978737
TI  - The neuropeptide Y Y1 receptor regulates leptin-mediated control of energy
      homeostasis and reproductive functions.
AB  - The orexigenic neurotransmitter neuropeptide Y (NPY) plays a central role in the
      hypothalamic control of food intake and energy balance. NPY also exerts an
      inhibition of the gonadotrope axis that could be important in the response to
      poor metabolic conditions. In contrast, leptin provides an anorexigenic signal to
      centrally control the body needs in energy. Moreover, leptin contributes to
      preserve adequate reproductive functions by stimulating the activity of the
      gonadotrope axis. It is of interest that hypothalamic NPY represents a primary
      target of leptin actions. To evaluate the importance of the NPY Y1 and Y5
      receptors in the downstream pathways modulated by leptin and controlling energy
      metabolism as well as the activity of the gonadotrope axis, we studied the
      effects of leptin administration on food intake and reproductive functions in
      mice deficient for the expression of either the Y1 or the Y5 receptor.
      Furthermore, the role of the Y1 receptor in leptin resistance was determined in
      leptin-deficient ob/ob mice bearing a null mutation in the NPY Y1 locus. Results
      point to a crucial role for the NPY Y1 receptor in mediating the NPY pathways
      situated downstream of leptin actions and controlling food intake, the onset of
      puberty, and the maintenance of reproductive functions.

PMID- 11978738
TI  - Effects of reactive gamma-ketoaldehydes formed by the isoprostane pathway
      (isoketals) and cyclooxygenase pathway (levuglandins) on proteasome function.
AB  - Oxidative stress can impair proteasome function, both of which are features of
      neurodegenerative diseases. Inhibition of proteasome function leads to protein
      accumulation and cell death. We discovered recently the formation of highly
      reactive g-ketoaldehydes, isoketals (IsoKs), and neuroketals (NeuroKs) as
      products of the isoprostane and neuroprostane pathways of free radical-induced
      lipid peroxidation that are analogous to cyclooxygenase-derived levuglandins
      (LGs). Because aldehydes that are much less reactive than IsoKs have been shown
      to inhibit proteasome function, we explored the ability of the proteasome to
      degrade IsoK-adducted proteins/peptides and the effect of IsoK and IsoK-adducted
      proteins/peptides on proteasome function. Adduction of IsoK to model proteasome
      substrates significantly reduced their rate of degradation by the 20S proteasome.
      The ability of IsoK to inhibit proteasome function directly was observed only at
      very high concentrations. However, at much lower concentrations, an IsoK-adducted
      protein (ovalbumin) and peptide (Ab1-40) significantly inhibited chymotrypsin
      like activity of the 20S proteasome. Moreover, incubation of IsoK with P19
      neuroglial cultures dose-dependently inhibited proteasome activity (IC50 = 330
      nM) and induced cell death (LC50 = 670 nM). These findings suggest that
      IsoKs/NeuroKs/LGs can inhibit proteasome activity and, if overproduced, may have
      relevance to the pathogenesis of neurodegenerative diseases.

PMID- 11978739
TI  - A novel control mechanism based on GDNF modulation of somatostatin release from
      sensory neurones.
AB  - Small-diameter sensory neurones found in the rat dorsal root ganglia (DRG)
      include cells sensitive to glial cell line-derived neurotrophic factor (GDNF),
      which express the inhibitory peptide somatostatin (SOM). Here we addressed the
      functional relationship between GDNF and sensory neurone-derived SOM. Topical
      application of GDNF through the rat isolated dorsal horn of the spinal cord
      promoted activity-induced release of SOM from central terminals of sensory
      neurones. Once released by sensory neurones, SOM is known to act, at least in
      part, by opposing the action of Substance P (SP) in neurogenic inflammation.
      Therefore, we evaluated GDNF ability to modulate two well-documented effects of
      peripherally and centrally administered SP. Local application of GDNF in the
      mouse air pouch reduced SP-induced leukocyte migration. This effect of GDNF was
      mimicked by the SOM analog octreotide (OCT) and required intact SOM neuronal
      pools. Intrathecal injection of GDNF activated rat lumbar dorsal horn neurones
      and inhibited intrathecal SP-induced thermal hypersensitivity. This effect of
      GDNF was reversed by the SOM antagonist c-SOM and mimicked by OCT. In conclusion
      we propose GDNF regulation of neuronal SOM release as a novel mechanism that, if
      explored, may lead to new therapeutic strategies based on local release of
      somatostatin.

PMID- 11978740
TI  - Werner syndrome diploid fibroblasts are sensitive to 4-nitroquinoline-N-oxide and
      8-methoxypsoralen: implications for the disease phenotype.
AB  - The clinical phenotype of Werner Syndrome (WRN) includes features reminiscent of
      accelerated aging and an increased incidence of sarcomas and other tumors of
      mesenchymal origin. This syndrome results from mutations in the WRN DNA
      helicase/exonuclease gene. We found that WRN deficient primary fibroblasts, as
      well as lymphoblastoid cell lines (LCLs), show reduced proliferative survival in
      response to 4-nitroquinoline-N-oxide (4NQO) and 8-methoxypsoralen (8MOP),
      compared with WRN-proficient cells. This is the first demonstration of drug
      hypersensitivity in primary cells of mesenchymal origin from WRN patients.
      Notably, 8MOP-induced DNA interstrand crosslinks, but not 8MOP mono-adducts,
      produced S-phase apoptosis in WRN-deficient LCLs. In contrast, 8MOP did not
      induce S-phase apoptosis in WRN-deficient diploid fibroblasts, in which drug
      hypersensitivity was entirely due to reduced cell proliferation. Such reduced
      proliferation of damaged mesenchymal cells in WRN patients may lead to earlier
      proliferative senescence. In addition, failure of WRN-deficient mesenchymal cells
      to undergo apoptosis in response to DNA damage in S-phase may promote genomic
      instability and could help clarify the increased risk of sarcoma in WRN patients.
      Because interstrand crosslinks are believed to be repaired through homologous
      recombination, these results suggest an important role for WRN in recombinational
      resolution of stalled replication forks.

PMID- 11978741
TI  - Socioeconomic status and preterm birth: New Zealand trends, 1980 to 1999.
AB  - BACKGROUND: While a number of countries have reported rising preterm birth rates
      over the past two decades, none has examined the effects of socioeconomic status
      on preterm birth at a national level. AIM: To document the changing incidence of
      preterm birth in New Zealand over the past 20 years and to determine whether
      particular socioeconomic or ethnic subsections of the population have contributed
      disproportionately to the changes seen. METHODS: Birth registration data
      routinely available from the New Zealand Health Information Service were analysed
      for the period 1980-99. Information for a total of 1 079 478 singleton live
      births was linked by Domicile Code to the New Zealand Deprivation Index, a small
      area index of deprivation. RESULTS: Singleton preterm birth rates rose by 37.2%
      during the 20 year period, from 4.3% in 1980 to 5.9% in 1999. Rates increased by
      71.9% among those living in the most affluent areas, but by only 3.5% among those
      living in the most deprived areas, resulting in the disappearance of a
      socioeconomic gradient in preterm birth that had existed during the early 1980s.
      CONCLUSIONS: This study challenges traditional thinking on the associations
      between socioeconomic status and preterm birth. Further research is necessary if
      the changes that have occurred in New Zealand over the past 20 years are to be
      fully understood.

PMID- 11978742
TI  - Effect of posture on oxygenation and respiratory muscle strength in convalescent
      infants.
AB  - OBJECTIVE: To determine if differences in respiratory muscle strength could
      explain any posture related effects on oxygenation in convalescent neonates.
      METHODS: Infants were examined in three postures: supine, supine with head up
      tilt of 45 degrees, and prone. A subsequent study was performed to determine the
      influence of head position in the supine posture. In each posture/head position,
      oxygen saturation (SaO2) was determined and respiratory muscle strength assessed
      by measurement of the maximum inspiratory pressure (PIMAX). PATIENTS: Twenty
      infants, median gestational age 34.5 weeks (range 25-43), and 10 infants, median
      gestational age 33 weeks (range 30-36), were entered into the first and second
      study respectively. RESULTS: Oxygenation was higher in the prone and supine with
      45 degrees head up tilt postures than in the supine posture (p<0.001), whereas
      PIMAX was higher in the supine and supine with head up tilt of 45 degrees
      postures than in the prone posture (p<0.001). Head position did not influence the
      effect of posture on PIMAX or oxygenation. CONCLUSION: Superior oxygenation in
      the prone posture in convalescent infants was not explained by greater
      respiratory muscle strength, as this was superior in the supine posture.

PMID- 11978743
TI  - Development of baroreflex control of heart rate in preterm and full term infants.
AB  - AIM: To study baroreflex maturation by measuring, longitudinally, baroreflex
      sensitivity in preterm (gestational age 24-37 weeks) and full term infants.
      METHODS: Baroreflex sensitivity was quantified once a week, one to seven times,
      by a totally non-invasive method. RESULTS: Baroreflex sensitivity at birth was
      lower in the preterm infant and increased with gestational age. It also increased
      with postnatal age, but the values for the preterm infants at term still tended
      to be lower than the values for full term babies. CONCLUSION: Baroreflex control
      of heart rate is present in the premature infant, but is underdeveloped and
      increases with postnatal age. Ex utero maturation seems to be delayed compared
      with in utero maturation assessed by full term values. These results may reflect
      sympathovagal imbalance in preterm infants and could identify a population more
      vulnerable to stress.

PMID- 11978745
TI  - Parental stress in families of 2 year old extremely low birthweight infants.
AB  - OBJECTIVE: To compare the parental stress in the families of 2 year old extremely
      low birthweight (ELBW) infants with that in control families, and to compare the
      stress of mothers with that of fathers. METHODS: The study population included
      all parents of ELBW infants (birth weight < 1000 g and gestational age at least
      22 gestational weeks) born between 1 January 1996 and 31 December 1997 in
      Helsinki University Hospital and followed at the hospital's neuropaediatric
      department. The parents of full term, healthy infants born subsequent to each
      ELBW infant were eligible for the control group. The Swedish Parenthood Stress
      Questionnaire (SPSQ) translated into Finnish was completed by parents during the
      neurological assessment visit at 2 years of age. RESULTS: No significant
      differences were found in total SPSQ or subscale scores when mothers of ELBW
      infants were compared with control mothers. Nor did the scores of fathers of ELBW
      infants differ from the scores of control fathers. However, in the comparison of
      all mothers with all fathers, several differences were found: mothers indicated
      significantly more distress than fathers with respect to role restriction,
      incompetence, and spouse relationship problems, and fathers indicated
      significantly more distress on the social isolation subscale. CONCLUSION: The
      study shows that, although the birth of an ELBW infant is a stressful event for
      parents, most parents seem to have recovered well by the time the child has
      reached the age of 2. In both control families and those of ELBW infants, the
      overall stress of mothers seemed to be higher than that of fathers.

PMID- 11978744
TI  - Routine examination of the newborn and maternal satisfaction: a randomised
      controlled trial.
AB  - OBJECTIVE: To determine whether the routine examination of the newborn by a
      midwife compared with a junior paediatrician (SHO) affects maternal satisfaction
      with this examination. METHODS: Randomised controlled trial: 826 mother and baby
      pairs in a district general hospital in south east England were randomised to a
      paediatric SHO or a midwife for the routine newborn examination. Maternal
      satisfaction with the examination was analysed in relation to intervention group,
      process, and background variables. RESULTS: Some 81% of mothers reported that
      they were satisfied or very satisfied with the newborn examination. Mothers
      assigned to a midwife were more satisfied with the newborn examination (crude
      odds ratio (OR) 0.54 (95% confidence interval (CI) 0.39 to 0.75), p < 0.001).
      However, after provision of health education during the examination, continuity
      of care provided, and history of miscarriage had been controlled for, status of
      examiner was no longer related to maternal satisfaction (adjusted OR 0.82 (95% CI
      0.57-1.20), NS). The discussion of healthcare issues by the examiner (adjusted OR
      0.49 (95% CI 0.34 to 0.70), p < 0.001) and continuity of care (adjusted OR 0.43
      (95% CI 0.23 to 0.81), p < 0.01) were both related to enhanced satisfaction, and
      history of miscarriage (adjusted OR 1.61 (1.08 to 2.40), p < 0.05) was associated
      with lower maternal satisfaction with the newborn examination. Midwives (61%)
      were more likely than SHOs (33%) to discuss healthcare issues, such as feeding,
      sleeping, and skin care. CONCLUSIONS: Mothers were more likely to be satisfied
      with the newborn examination by a midwife than an SHO because midwives were more
      likely to discuss healthcare issues during the examination and were able to
      provide continuity of care. However, midwife examinations according to exclusion
      criteria agreed with trial midwives excluded half of all newborns, and criteria
      may have to be reconsidered for practice implementation.

PMID- 11978746
TI  - Phenobarbitone, neonatal seizures, and video-EEG.
AB  - AIMS: To evaluate the effectiveness of phenobarbitone as an anticonvulsant in
      neonates. METHODS: An observational study using video-EEG telemetry. Video-EEG
      was obtained before treatment was started, for an hour after treatment was given,
      two hours after treatment was given, and again between 12 and 24 hours after
      treatment was given. Patients were recruited from all babies who required
      phenobarbitone (20-40 mg/kg intravenously over 20 minutes) for suspected clinical
      seizures and had EEG monitoring one hour before and up to 24 hours after the
      initial dose. An EEG seizure discharge was defined as a sudden repetitive
      stereotyped discharge lasting for at least 10 seconds. Neonatal status
      epilepticus was defined as continuous seizure activity for at least 30 minutes.
      Seizures were categorised as EEG seizure discharges only (electrographic), or as
      EEG seizure discharges with accompanying clinical manifestations
      (electroclinical). Surviving babies were assessed at one year using the Griffiths
      neurodevelopmental score. RESULTS: Fourteen babies were studied. Four responded
      to phenobarbitone; these had normal or moderately abnormal EEG background
      abnormalities and outcome was good. In the other 10 babies electrographic
      seizures increased after treatment, whereas electroclinical seizures reduced.
      Three babies were treated with second line anticonvulsants, of whom two
      responded. One of these had a normal neurodevelopmental score at one year, but
      the outcome for the remainder of the whole group was poor. CONCLUSION:
      Phenobarbitone is often ineffective as a first line anticonvulsant in neonates
      with seizures in whom the background EEG is significantly abnormal.

PMID- 11978747
TI  - Magnetic resonance imaging of the infant brain: anatomical characteristics and
      clinical significance of punctate lesions.
AB  - OBJECTIVE: To describe the magnetic resonance imaging (MRI) characteristics of
      punctate brain lesions in neonates (number, appearance, distribution, and
      association with other brain abnormalities) and to relate them to
      neurodevelopmental outcome. METHODS: A retrospective analysis was performed of
      110 MRI brain scans from 92 infants admitted in 1998 to the neonatal intensive
      care unit. Results of routine neurodevelopmental follow up (1998-2001) in those
      infants with punctate brain lesions were analysed. RESULTS: Punctate lesions were
      observed in 15/50 preterm and 2/42 term infants. In the preterm group, the number
      of lesions was < 3 in 20%, 3-10 in 27%, and > 10 in 53%. In 14/15 the lesions
      were linearly organised and located in the centrum semiovale. Other brain
      abnormalities were absent or minor--that is, "isolated" punctate lesions--in 8/15
      and major in 7/15. In the term group, punctate lesions were organised in clusters
      and no other brain abnormalities were observed. Isolated punctate lesions were
      observed in 10/17 infants, and a normal neurodevelopmental outcome was seen in
      9/10 (mean follow up 29.5 months). One infant showed a slight delay in language
      development. In the infants with associated brain lesions (7/17, mean follow up
      27.5 months), outcome was normal in only two subjects. CONCLUSIONS: Punctate
      lesions are predominantly seen in preterm infants, are usually linearly
      organised, and border the lateral ventricles. Isolated punctate lesions may imply
      a good prognosis, because most of these subjects have a normal neurodevelopmental
      outcome so far.

PMID- 11978748
TI  - Supplementation of a bovine milk formula with an oligosaccharide mixture
      increases counts of faecal bifidobacteria in preterm infants.
AB  - BACKGROUND: The establishment of a balanced intestinal microflora which may
      protect against infection is desirable for the preterm infant. OBJECTIVE: To
      investigate the effect of a preterm formula milk supplement consisting of
      oligosaccharides in similar proportions to human milk on the faecal flora and
      stool characteristics of preterm infants. STUDY DESIGN: To resemble the effect of
      human milk, an oligosaccharide mixture consisting of 90% galacto-oligosaccharides
      and 10% fructo-oligosaccharides was used to supplement a standard preterm formula
      at a concentration of 10 g/l. This supplemented formula was studied in 15 preterm
      infants, and the results were compared with those found in 15 infants fed a
      formula supplemented with maltodextrin as placebo. A group fed fortified mother's
      milk was investigated as a reference group (n = 12). On four days during a 28 day
      feeding period (1, 7, 14, and 28), the faecal flora was investigated, and stool
      characteristics, growth, and possible side effects were recorded. RESULTS: During
      the study period, the number of bifidobacteria in the group fed the
      oligosaccharide supplemented formula increased to the upper range of
      bifidobacteria counts in the reference group. The difference between the
      supplemented and non-supplemented groups was highly significant (p = 0.0008). The
      stool characteristics were also influenced by the supplement: the stool frequency
      after 28 days was significantly lower in the control group than in the
      oligosaccharide supplemented group (p = 0.0079) and the reference group (p <
      0.0001). Over the study period, the stool consistency in the control group became
      harder, but remained fairly stable in the other two groups. There was no effect
      of the different diets on the incidence of side effects (crying, regurgitation,
      vomiting) or on weight gain or length gain. CONCLUSION: Supplementing preterm
      formula with a mixture of galacto- and fructo-oligosaccharides at a concentration
      of 10 g/l stimulates the growth of bifidobacteria in the intestine and results in
      stool characteristics similar to those found in preterm infants fed human milk.
      Therefore prebiotic mixtures such as the one studied may help to improve
      intestinal tolerance to enteral feeding in preterm infants.

PMID- 11978750
TI  - Evaluation of the HemoCue compared with the Coulter STKS for measurement of
      neonatal haemoglobin.
AB  - OBJECTIVE: To compare the measurement of haemoglobin concentration ([Hb]) using
      the HemoCue haemoglobinometer with that using the Coulter STKS haemoglobinometer.
      DESIGN: Thirty two EDTA samples were taken from neonates. [Hb] was measured in
      these samples using the HemoCue; the samples were then transferred to the
      haematology laboratory for [Hb] determination with the Coulter STKS. In addition,
      [Hb] was determined in 50 different random EDTA neonatal samples already held in
      the laboratory, using the HemoCue and Coulter STKS. PATIENTS: Neonates in the
      intensive care and low dependency Units of the Royal Devon and Exeter Hospital.
      INTERVENTIONS: Samples were collected from arterial lines or by venepuncture or
      heel prick into an EDTA bottle. MAIN OUTCOME MEASURES: [Hb] using the HemoCue and
      Coulter STKS methods. RESULTS: The mean [Hb] measured using the HemoCue was 150.3
      g/l (range 78-215) compared with 152.8 g/l (range 78-217) measured using the
      Coulter STKS, with a mean of the differences of 2.5 g/l. The standard deviation
      of the differences of the 82 samples was 3.73 g/l. The limits of agreement of the
      two methods (mean difference +/- 2SD) were -4.8 to +9.8 g/l. CONCLUSION: With
      adequate training and monitoring, the HemoCue can be used directly on the
      neonatal unit for rapid determination of [Hb] to within 7.5 g/l compared with the
      laboratory Coulter STKS, using much smaller sample volumes.

PMID- 11978749
TI  - Changes in haemoglobin levels in infants in Malawi: effect of low birth weight
      and fetal anaemia.
AB  - OBJECTIVES: To examine the effect of low birth weight (LBW) and fetal anaemia
      (FA) on haemoglobin (Hb) patterns in infancy. To study the additional
      contribution of other risk factors known at birth. To examine the effect of iron
      supplementation during infancy on Hb levels. METHODS: A stratified cohort of
      infants in Malawi (83 with LBW (< 2500 g), 111 with FA (cord Hb < 125 g/l), 31
      with both LBW and FA, and 176 controls) was followed during infancy. Hb levels
      were measured at about 2, 4, 6, 9, and 12 months of age. Repeated measures models
      were used to describe the changes in Hb levels over time. RESULTS: The mean Hb
      concentration in the control group was 95.5 g/l (95% confidence interval (CI)
      92.5 to 98.5) at 2 months, 86.9 g/l (95% CI 84.4 to 89.4) at 9 months, and 898
      g/l (95% CI 874 to 92.2) at 12 months. Differences between LBW infants and
      controls increased over time (difference at 12 months: 5.5 g/l (95% CI 1.3 to
      9.7)). Infants with FA had borderline significantly lower Hb at 2 months (p =
      0.07), but at 6 months their levels were similar to those of controls. The LBW
      infants and those with FA had the lowest Hb levels (difference from controls at
      12 months 7.9 g/l). Parity, placental and maternal malaria at delivery, and sex
      significantly affected Hb levels after adjustment for LBW and FA. After iron
      supplementation, Hb significantly increased. CONCLUSIONS: Antimalarial control
      and iron supplementation throughout pregnancy should be increased to reduce the
      incidence of infant anaemia and improve child development and survival.

PMID- 11978751
TI  - Can transcutaneous bilirubinometry reduce the need for blood tests in jaundiced
      full term babies?
AB  - BACKGROUND: Previous studies have suggested that transcutaneous bilirubinometry
      (TcB) may provide a useful method for screening for significant jaundice, thereby
      reducing unnecessary blood tests. These studies have not allowed an estimation of
      the magnitude of such a benefit. OBJECTIVES: To evaluate the accuracy of TcB as a
      method of determining the need for serum bilirubin (SBR) measurements in full
      term babies and to quantify the magnitude of any benefit. SUBJECTS: Babies born
      at more than 34 weeks gestation who had not previously been exposed to
      phototherapy and were requiring blood sampling in the first week of life. METHOD:
      TcB measurements were made at the same time as blood sampling. SBR was measured
      in all blood samples. For jaundiced babies, the ability of TcB to detect
      significant jaundice (SBR > 249 micromol/l) was evaluated. RESULTS: There was a
      correlation between SBR and TcB measurements (n = 303, r = 0.76, p < 0.0001), but
      the 95% prediction interval for SBR from TcB was wide (+/- 88.3 micromol/l). For
      the 285 jaundiced babies, the area under the receiver operator characteristic
      curve was 0.89. A TcB value of 18 detected significant jaundice with a
      sensitivity of 100% and a specificity (95% confidence interval) of 45% (39% to
      51%). If blood samples had only been taken from babies with a TcB value greater
      than 18, the number of samples taken would have been reduced by 34%. CONCLUSIONS:
      SBR cannot be measured accurately by TcB. However, TcB measurements can be used
      to determine the need for blood sampling in jaundiced babies and will reduce the
      number of blood samples taken. Recent improvements in TcB may improve the
      performance of this method.

PMID- 11978753
TI  - Low levels of pancreatic elastase 1 in stools of preterm infants.
AB  - The amount of faecal pancreatic enzyme elastase 1 was significantly lower in 42
      preterm newborns than in 12 full term babies at day 2 (89 (3-539) v 354 (52-600)
      microg/g, p<0.0007) and day 5 (164 (3-600) v 600 (158-600) microg/g, p<0.05) and
      correlated positively with total nutrient intake during the first week of life in
      preterm infants. This should probably be taken into account during early feeding.

PMID- 11978752
TI  - Fibroblast mitogenic activity of lung lavage fluid from infants with chronic lung
      disease of prematurity.
AB  - BACKGROUND: Lung fibrosis is thought to be important in chronic lung disease of
      prematurity (CLD). METHODS: Fibroblast proliferative activity was assessed in 207
      bronchoalveolar lavage fluid (BALF) samples from 43 infants. Sixteen developed
      CLD (birth weight 765 g (630-1230), gestation 26.5 weeks (23-29)), 18 developed
      respiratory distress syndrome (RDS) (birth weight 1415 g (430-4160), gestation 31
      weeks (23-39)), and nine control infants (birth weight 2110 g (900-3720),
      gestation 32 weeks (26-41)) received mechanical ventilation for non-pulmonary
      reasons. RESULTS: The fibroblast proliferative activity relative to 10% fetal
      calf serum was 64-75% in infants with CLD, 55-86% in the RDS group, and 42-68% in
      control infants during the first 5 weeks of life. Only at day 3 was there a
      difference between the groups (CLD 72% v control 42%, p < 0.01; RDS 63% v control
      42%, p < 0.05). With the use of neutralising antibodies, platelet derived growth
      factor BB (PDGF-BB) and epidermal growth factor were undetectable, and insulin
      like growth factor I (IGF-I) accounted for 14% (p < 0.05) and 11% (p < 0.005) of
      BALF mitogenic activity from the RDS and CLD groups respectively. CONCLUSIONS:
      The mitogenic activity of BALF was similar in the three groups studied and was
      only partially accounted for by IGF-I. Growth factors other than PDGF-BB and IGF
      I contribute significantly to this process.

PMID- 11978754
TI  - Neonatal alloimmune thrombocytopenia with significant HLA antibodies.
AB  - A case of neonatal alloimmune thrombocytopenia (NAIT) secondary to human platelet
      antigen (HPA)-1a antibodies is reported. Additional multispecific HLA antibodies
      rendered volunteer donor platelet transfusions ineffective. Despite a high
      incidence of maternal HLA antibodies in the pregnant population, there is only
      one previous report of clinically significant HLA antibodies.

PMID- 11978755
TI  - Neonatal pneumatocele as a complication of nasal continuous positive airway
      pressure.
AB  - A preterm infant with mild respiratory insufficiency resulting from respiratory
      distress syndrome developed a pneumatocele after the start of nasal continuous
      positive airway pressure. Pneumonia was excluded by sputum and blood cultures.
      Treatment with high frequency oscillation ventilation resulted in complete
      recovery.

PMID- 11978756
TI  - Exogenous Pseudomonas endophthalmitis: a cause of lens enucleation.
AB  - Pseudomonas aeruginosa eye infection, although uncommon, may be a devastating
      disease if not recognised and treated appropriately, especially in premature
      infants. The case is presented of a premature baby who lost her right eye from
      invasive exogenous Ps aeruginosa eye infection.

PMID- 11978757
TI  - Sir James Young Simpson (1811-1870) and obstetric anaesthesia.
AB  - Sir James Young Simpson of Edinburgh became famous for his discovery of the
      anaesthetic qualities of chloroform and his championship of obstetric
      anaesthesia. However, as the outstanding British obstetrician between 1840 and
      1870, he also pioneered many other advances in obstetrics.

PMID- 11978758
TI  - Examination of the neonatal palate.

PMID- 11978759
TI  - Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor
      cell degeneration.
AB  - The canine disease, X-linked progressive retinal atrophy (XLPRA), is similar to
      human RP3, an X-linked form of retinitis pigmentosa, and maps to the same region
      in the X chromosome. Analysis of the physical map of the XLPRA and RP3 intervals
      shows a high degree of conservation in terms of genes and their order. We have
      found different mutations in exon ORF15 of the RPGR gene in two distinct mutant
      dog strains (XLPRA1, XLPRA2). Microdeletions resulting in a premature stop or a
      frameshift mutation result in very different retinal phenotypes, which are allele
      specific and consistent for each mutation. The phenotype associated with the
      frameshift mutation in XLPRA2 is very severe and manifests during retinal
      development; the phenotype resulting from the XLPRA1 nonsense mutation is
      expressed only after normal photoreceptor morphogenesis. Splicing of RPGR mRNA
      transcripts in retina is complex, and either exon ORF15 or exon 19 can be a
      terminal exon. The retina-predominant transcript contains ORF15 as a terminal
      exon, and is expressed in normal and mutant retinas. The frameshift mutation
      dramatically alters the deduced amino acid sequence, and the protein aggregates
      in the endoplasmic reticulum of transfected cells. The cellular and molecular
      results in the two canine RPGR exon ORF15 mutations have implications for
      understanding the phenotypic variability found in human RP3 families that carry
      similar mutations.

PMID- 11978760
TI  - Murine model of autosomal dominant retinitis pigmentosa generated by targeted
      deletion at codon 307 of the rds-peripherin gene.
AB  - We introduced a targeted single base deletion at codon 307 of the rds-peripherin
      gene in mice, similar mutations being known to cause autosomal dominant retinitis
      pigmentosa (RP) in man. Histopathological and electroretinographic analysis
      indicate that the retinopathy in mice homozygous for the codon 307 mutation
      appears more rapid than that in the naturally occurring null mutant, the rds(-/-)
      mouse, suggesting that the rds-307 mutation displays a dominant negative
      phenotype in combination with that due to haplosufficiency. RP is the most
      prevalent cause of registered visual handicap in those of working age in
      developed countries, the 50 or so mutations so far identified within the RDS
      peripherin gene accounting for up to 10% of dominant cases of the disease. Given
      the sequence homologies that exist between the murine rds-peripherin and the
      human RDS-peripherin gene, this disease model, the first to be generated for
      peripherin-based RP using gene targeting techniques, should in principle be of
      value in the work-up in mice of therapeutics capable of targeting transcripts
      derived from the human gene.

PMID- 11978761
TI  - A novel association of the SMN protein with two major non-ribosomal nucleolar
      proteins and its implication in spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is caused by the loss of functional survival motor
      neuron 1 (SMN1) protein. This ubiquitously expressed protein is a component of a
      novel complex immunodetected in both the cytoplasm and the nucleus, which is
      associated with complexes involved in mRNA splicing, ribosome biogenesis and
      transcription. Here, we study a mutant protein corresponding to the N-terminal
      half of the protein that is encoded by the SMA frameshift mutation SMN 472del5.
      We show by confocal microscopy that the resulting mutant protein exhibits various
      distribution patterns in different transiently transfected COS cells. The mutant
      distributes into the nucleoplasm and/or the nucleolus, whereas the normal SMN
      protein accumulates at discrete nucleocytoplasmic dot-like structures previously
      named gems/Cajal bodies. The cell population with the nucleolar distribution is
      enriched upon treatment with mimosine, a synchronizing drug in late G(1) phase.
      Co-immunoprecipitation studies carried out on nuclear extracts reveal that both
      the endogenous SMN and mutant proteins are associated with complexes containing
      two major non-ribosomal nucleolar proteins, namely nucleolin and protein B23, and
      that the association is mediated, by among other things, RNA moieties. Both the
      association of the SMN protein with nucleolin-containing complexes and the
      nucleolin/B23 complex are disrupted in fibroblasts derived from a type I SMA
      patient harboring a homozygous SMN1 gene deletion. These findings suggest that
      altered assembly and/or stability of ribonucleoprotein complexes may contribute
      to the pathophysiological processes in SMA.

PMID- 11978762
TI  - VSX1: a gene for posterior polymorphous dystrophy and keratoconus.
AB  - We identified mutations in the VSX1 homeobox gene for two distinct inherited
      corneal dystrophies; posterior polymorphous dystrophy (PPD) and keratoconus. One
      of the mutation (R166W) responsible for keratoconus altered the homeodomain and
      impaired DNA binding. Two other sequence changes (L159M and G160D) were
      associated with keratoconus and PPD, respectively, and involved a region adjacent
      to the homeodomain. The G160D substitution, and a fourth defect affecting the
      highly conserved CVC domain (P247R), occurred in a child with very severe PPD who
      required a corneal transplant at 3 months of age. In this family, relatives with
      the G160D change alone had mild to moderate PPD, while P247R alone caused no
      corneal abnormalities. However, with either the G160D or P247R mutation,
      electroretinography detected abnormal function of the inner retina, where VSX1 is
      expressed. These data define the molecular basis of two important corneal
      dystrophies and reveal the importance of the CVC domain in the human retina.

PMID- 11978763
TI  - Identification of a novel family of presenilin homologues.
AB  - Presenilin 1 and presenilin 2 are polytopic membrane proteins, whose genes are
      mutated in some individuals with Alzheimer's disease. Presenilins have been shown
      to influence limited proteolysis of amyloid beta protein precursor (APP), Notch
      and ErbB4, and have been proposed to be gamma-secretases that perform the
      terminal cleavage of APP. In this model, two conserved and apparently
      intramembranous aspartic acids participate in catalysis. Highly sequence-similar
      presenilin homologues are known in plants, invertebrates and vertebrates. In this
      work, we have used a combination of different sequence database search methods to
      identify a new family of proteins homologous to presenilins. Members of this
      family, which we term presenilin homologues (PSH), have significant sequence
      similarities to presenilins and also possess two conserved aspartic acid residues
      within adjacent predicted transmembrane segments. The PSH family is found
      throughout the eukaryotes, in fungi as well as plants and animals, and in
      archaea. Five PSHs are detectable in the human genome, of which three possess
      "protease-associated" domains that are consistent with the proposed protease
      function of PSs. Based on these findings, we propose that PSs and PSHs represent
      different sub-branches of a larger family of polytopic membrane-associated
      aspartyl proteases.

PMID- 11978764
TI  - Identification of transcriptional targets for Six5: implication for the
      pathogenesis of myotonic dystrophy type 1.
AB  - Myotonic dystrophy 1 (DM1) is the most common inherited neuromuscular disease in
      adults. The disorder, characterized by myotonia, muscle wasting and weakness,
      cataract, insulin resistance, and mental impairment, is caused by the expansion
      of an unstable CTG repeat located in the 3' untranslated region of DMPK. The
      repeat expansion suppresses the expression of the homeobox gene SIX5. We describe
      here an experimental system to identify downstream transcriptional targets of
      mouse Six5 in order to elucidate the role of SIX5 in the pathogenesis of DM1 and
      development. By overexpressing a constitutively active Six5 (VP16-Six5wt) using
      adenovirus-mediated gene transfer in P19 cells and subsequent expression
      profiling using cDNA arrays, 21 genes, whose expression level increased by the
      treatment, were identified as potential target genes. Genes expressed in the
      somites, skeletal muscles, brain and meninges comprised the majority, suggesting
      the role of Six5 in the development and function of mesodermal tissues and brain.
      We provide evidence that Igfbp5 encoding a component of IGF signaling is a direct
      Six5-target. Moreover, the overall expression level of Igfbp5 was decreased in
      Six5-deficient mouse fibroblasts, and the response of human IGFBP5 to MyoD
      induced muscle conversion was altered in cells of DM1 patients. Our results not
      only identify Six5 as an activator that directs Igfbp5 expression but also
      suggest that reduced SIX5 expression in DM1 might contribute to specific aspects
      of the DM1 phenotype.

PMID- 11978765
TI  - Gene complementation of airway epithelium in the cystic fibrosis mouse is
      necessary and sufficient to correct the pathogen clearance and inflammatory
      abnormalities.
AB  - Increasingly, cystic fibrosis (CF) is regarded as an inflammatory disorder where
      the response of the lung to Pseudomonas aeruginosa is exaggerated as a
      consequence of processes mediated by the product of the CF gene, CFTR. Of
      importance to any gene-replacement strategy for treatment of CF is the
      identification of the cell type(s) within the lung milieu that need to be
      corrected and an indication whether this is sufficient to restore a normal
      inflammatory response and bacterial clearance. We generated G551D CF mice
      transgenically expressing the human CFTR gene in two tissue compartments
      previously demonstrated to mediate a CFTR-dependent inflammatory response: lung
      epithelium and alveolar macrophages. Following chronic pulmonary infection with
      P. aeruginosa, CF mice with epithelial-expressed but not macrophage-specific CFTR
      showed an improvement in pathogen clearance and inflammatory markers compared
      with control CF animals. Additionally, these data indicate the general role for
      epithelial cell-mediated events in the response of the lung to bacterial
      pathogens and the importance of CFTR in mediating these processes.

PMID- 11978766
TI  - A nonsense mutation in the enamelin gene causes local hypoplastic autosomal
      dominant amelogenesis imperfecta (AIH2).
AB  - Amelogenesis imperfecta (AI) is an inherited tooth disorder affecting tooth
      enamel formation only. A gene for autosomal dominant AI, the local hypoplastic
      form, has been localized to a 4 Mb region on chromosome 4q (AIH2). The enamelin
      gene (ENAM ), has been mapped to chromosome 4q21, to the same region as AIH2, and
      was recently shown to be mutated in patients with smooth and thin hypoplastic
      autosomal dominant AI (ADAI). In this study, we describe an ENAM mutation causing
      the local hypoplastic form of ADAI, a phenotype that accounts for 27% of the
      autosomally inherited cases in Northern Sweden. This nonsense mutation in the
      enamelin gene results in a truncated peptide of 52 amino acids as compared with
      1142 amino acids of the normal protein. Our results show that while a splice site
      mutation is associated with smooth and thin hypoplastic AI, a base substitution
      resulting in a shorter peptide causes local hypoplasia of the enamel, a milder
      form of AI. These findings support ENAM as a disease gene, and shed new light on
      the molecular mechanism of the disease and to the function of the enamelin
      protein in enamel formation.

PMID- 11978767
TI  - YAC transgenic mice carrying pathological alleles of the MJD1 locus exhibit a
      mild and slowly progressive cerebellar deficit.
AB  - Machado-Joseph disease (MJD; MIM 109150) is a late-onset neurodegenerative
      disorder caused by the expansion of a polyglutamine tract within the MJD1 gene.
      We have previously reported the generation of human yeast artificial chromosome
      (YAC) constructs encompassing the MJD1 locus into which expanded (CAG)(76) and
      (CAG)(84) repeat motifs have been introduced by homologous recombination.
      Transgenic mice containing pathological alleles with polyglutamine tract lengths
      of 64, 67, 72, 76 and 84 repeats, as well as the wild type with 15 repeats, have
      now been generated using these YAC constructs. The mice with expanded alleles
      demonstrate a mild and slowly progressive cerebellar deficit, manifesting as
      early as 4 weeks of age. As the disease progresses, pelvic elevation becomes
      markedly flattened, accompanied by hypotonia, and motor and sensory loss.
      Neuronal intranuclear inclusion (NII) formation and cell loss is prominent in the
      pontine and dentate nuclei, with variable cell loss in other regions of the
      cerebellum from 4 weeks of age. Interestingly, peripheral nerve demyelination and
      axonal loss is detected in symptomatic mice from 26 weeks of age. In contrast,
      transgenic mice carrying the wild-type (CAG)(15) allele of the MJD1 locus appear
      completely normal at 20 months. Disease severity increases with the level of
      expression of the expanded protein and the size of the repeat. These mice are
      representative of MJD and will be a valuable resource for the detailed analysis
      of the roles of repeat length, tissue specificity and level of expression in the
      neurodegenerative processes underlying MJD pathogenesis.

PMID- 11978768
TI  - Expression of Dp260 in muscle tethers the actin cytoskeleton to the dystrophin
      glycoprotein complex and partially prevents dystrophy.
AB  - Dystrophin forms a mechanical link between the actin cytoskeleton and the
      extracellular matrix in muscle that helps maintain sarcolemmal integrity. Two
      regions of dystrophin have been shown to bind actin: the N-terminal domain and
      rod domain repeats 11-17. To better understand the roles of these two domains and
      whether the rod domain actin-binding domain alone can support a mechanically
      functional link with actin, we constructed transgenic mice expressing Dp260 in
      skeletal muscle. Dp260, the retinal isoform of dystrophin, lacks the N-terminal
      domain and a significant portion of the rod domain, but retains the rod domain
      actin-binding domain. Our results indicate that Dp260 expression restores a
      stable association between costameric actin and the sarcolemma, assembles the
      dystrophin-glycoprotein complex, and significantly slows the progression of the
      dystrophy in the dystrophin-deficient mdx mouse. We assessed the functional
      integrity of the mechanical link in Dp260 transgenic mdx mice and found that
      Dp260 muscles showed normal resistance to contraction-induced injury, but
      dramatic reductions in force generation similar to those found with mdx muscles.
      Morphologically, Dp260 muscles displayed reduced amounts of inflammation and
      fibrosis, but still showed a significant, albeit reduced, amount of
      degeneration/regeneration. These data demonstrate that protection from
      contraction-induced injury can dramatically ameliorate, but not completely halt,
      the dystrophic process. We suggest that a non-mechanical defect, attributed to
      the loss of the N terminus of dystrophin, is likely responsible for the residual
      dystrophy observed.

PMID- 11978769
TI  - Aggregate-prone proteins with polyglutamine and polyalanine expansions are
      degraded by autophagy.
AB  - Protein conformational disorders (PCDs), such as Alzheimer's disease,
      Huntington's disease (HD), Parkinson's disease and oculopharyngeal muscular
      dystrophy, are associated with proteins that misfold and aggregate. Here we have
      used exon 1 of the HD gene with expanded polyglutamine [poly(Q)] repeats and
      enhanced green fluorescent protein tagged to 19 alanines as models for aggregate
      prone proteins, to investigate the pathways mediating their degradation.
      Autophagy is involved in the degradation of these model proteins, since they
      accumulated when cells were treated with different inhibitors acting at distinct
      stages of the autophagy-lysosome pathway, in two different cell lines.
      Furthermore, rapamycin, which stimulates autophagy, enhanced the clearance of our
      aggregate-prone proteins. Rapamycin also reduced the appearance of aggregates and
      the cell death associated with the poly(Q) and polyalanine [poly(A)] expansions.
      Since rapamycin is used clinically, this drug or related analogues may be
      suitable candidates for therapeutic investigation in HD and related diseases. We
      have also re-examined the role of the proteasome, since previous studies in
      poly(Q) diseases have used lactacystin as an inhibitor--recent studies have shown
      that lactacystin may also affect lysosomal function. Both lactacystin and the
      specific proteasomal inhibitor epoxomicin increased soluble protein levels of the
      poly(Q) constructs, suggesting that these are also cleared by the proteasome.
      However, while poly(Q) aggregation was enhanced by lactacystin in our inducible
      PC12 cell model, aggregation was reduced by epoxomicin, suggesting that some
      other protein(s) induced by epoxomicin may regulate poly(Q) aggregation.

PMID- 11978770
TI  - Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral
      temporal epilepsy.
AB  - Autosomal dominant lateral temporal epilepsy (EPT; OMIM 600512) is a form of
      epilepsy characterized by partial seizures, usually preceded by auditory signs.
      The gene for this disorder has been mapped by linkage studies to chromosomal
      region 10q24. Here we show that mutations in the LGI1 gene segregate with EPT in
      two families affected by this disorder. Both mutations introduce premature stop
      codons and thus prevent the production of the full-length protein from the
      affected allele. By immunohistochemical studies, we demonstrate that the LGI1
      protein, which contains several leucine-rich repeats, is expressed ubiquitously
      in the neuronal cell compartment of the brain. Moreover, we provide evidence for
      genetic heterogeneity within this disorder, since several other families with a
      phenotype consistent with this type of epilepsy lack mutations in the LGI1 gene.

PMID- 11978771
TI  - Pallister-Hall syndrome phenotype in mice mutant for Gli3.
AB  - Mutations in the GLI3 gene have been identified in several human malformation
      syndromes. One of these autosomal dominant developmental disorders is Pallister
      Hall syndrome (PHS; MIM146510), which is associated with central polydactyly and
      other malformations. Interestingly, the mutations in the GLI3 transcription
      factor gene identified in patients with PHS are restricted to the region 3' of
      the zinc finger-encoding domain, leaving this DNA-binding domain intact. We have
      investigated the consequences of this mutation on the development of multiple
      organ systems by introducing a targeted mutation in mice. We found that mice
      homozygous for the mutation showed a central polydactyly, thus modeling one of
      the major abnormalities of the human syndrome. Moreover, Gli3-mutant mice
      displayed a wide range of developmental abnormalities encompassing almost all of
      the common PHS features, including imperforate anus, gastrointestinal, epiglottis
      and larynx defects, abnormal kidney development, and absence of adrenal glands.
      Thus, our Gli3-mutant mice provide an excellent model for studies of both the
      pathogenesis of PHS and Gli3 functions in the development of the affected organ
      systems.

PMID- 11978772
TI  - Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the
      increase of reactive oxygen species caused by huntingtin.
AB  - Neuronal loss and intraneuronal protein aggregates are characteristics of
      Huntington's disease (HD), which is one of 10 known neurodegenerative disorders
      caused by an expanded polyglutamine [poly(Q)] tract in the disease protein. N
      terminal fragments of mutant huntingtin produce intracellular aggregates and
      cause toxicity. Several studies have shown that chaperones suppress poly(Q)
      aggregation and toxicity/cell death, but the mechanisms by which they prevent
      poly(Q)-mediated cell death remain unclear. In the present study, we identified
      heat shock protein 27 (HSP27) as a suppressor of poly(Q) mediated cell death,
      using a cellular model of HD. In contrast to HSP40/70 chaperones, we showed that
      HSP27 suppressed poly(Q) death without suppressing poly(Q) aggregation. We tested
      the hypotheses that HSP27 may reduce poly(Q)-mediated cell death either by
      binding cytochrome c and inhibiting the mitochondrial death pathway or by
      protecting against reactive oxygen species (ROS). While poly(Q)-induced cell
      death was reduced by inhibiting cytochrome c (cyt c) release from mitochondria,
      protection by HSP27 was regulated by its phosphorylation status and was
      independent of its ability to bind to cyt c. However, we observed that mutant
      huntingtin caused increased levels of ROS in neuronal and non-neuronal cells. ROS
      contributed to cell death because both N-acetyl-L-cysteine and glutathione in its
      reduced form suppressed poly(Q)-mediated cell death. HSP27 decreased ROS in cells
      expressing mutant huntingtin, suggesting that this chaperone protects cells
      against oxidative stress. We propose that a poly(Q) mutation can induce ROS that
      directly contribute to cell death and that HSP27 is an antagonist of this
      process.

PMID- 11978773
TI  - Identification and expression of mouse Langerin (CD207) in dendritic cells.
AB  - We have cloned the mouse homologue of human Langerin (h-Langerin), a type II
      transmembrane protein with a single external C-type lectin domain. Mouse Langerin
      (m-Langerin) displays 65 and 74% homologies in total amino acid and lectin
      domains with those of h-Langerin. The cognate mouse and rat genes were assigned
      to chromosome 6D1-D2 and chromosome 4q33 distal-q34.1 proximal respectively,
      syntenic to the h-Langerin gene on chromosome 2p13. With RT-PCR, m-Langerin
      transcripts were as expected detected in MHC class II+, but not MHC class II-,
      cells from epidermis and the expression level was reduced by culture. However, m
      Langerin transcripts were also expressed in spleen, lymph nodes (LN), thymus,
      liver, lung and even heart, but not gut-associated lymphoid tissues. In single
      cell lymphoid suspensions, m-Langerin transcripts were mainly detected in the
      CD11c+ dendritic cells (DC), especially the CD11blow/CD8high fraction of spleen
      and LN. DC generated from bone marrow precursors by granulocyte macrophage colony
      stimulating factor (GM-CSF) expressed m-Langerin, but this was shut down during
      maturation with CD40 ligand or lipopolysaccharide. DC derived from blood
      monocytes by GM-CSF + IL-4 lacked m-Langerin unless the cultures were
      supplemented with transforming growth factor (TGF)-beta1. Unexpectedly,
      significant amounts of m-Langerin transcripts were detected in skin and LN of TGF
      beta1-deficient mice, although in much lower amounts than littermate controls.
      Recombinant m-Langerin could form multimers and bind to mannan-agarose. These
      findings indicate that Langerin expression is regulated at several levels: by TGF
      beta1, DC subsets, DC maturation and the tissue environment.

PMID- 11978774
TI  - BY55/CD160 acts as a co-receptor in TCR signal transduction of a human
      circulating cytotoxic effector T lymphocyte subset lacking CD28 expression.
AB  - In the present study, we examined the role of the recently identified
      glycosylphosphatidylinositol (GPI)-anchored cell surface molecule BY55, assigned
      as CD160, in TCR signaling. CD160 is expressed by most intestinal intraepithelial
      lymphocytes and by a minor subset of circulating lymphocytes including NK,
      TCRgammadelta and cytotoxic effector CD8bright+CD28- T lymphocytes. We report
      that CD160, which has a broad specificity for MHC class Ia and Ib molecules,
      behaves as a co-receptor upon T cell activation. Anti-CD160 mAb enhance the CD3
      induced proliferation of freshly isolated CD160-enriched peripheral blood
      lymphocytes and CD160+ T cell clones. Further, the engagement of CD160 receptors
      on normal clonal T lymphocyte populations lacking CD4, CD8 and CD28 molecules by
      MHC class I molecules results in an increased CD3-induced cell proliferation.
      Further, we found that CD160 co-precipitates with the protein tyrosine kinase
      p56lck and tyrosine phosphorylated zeta chains upon TCR-CD3 cell activation.
      Thus, we demonstrate that CD160 provides co-stimulatory signals leading to the
      expansion of a minor subset of circulating lymphocytes including double-negative
      CD4/CD8 T lymphocytes and CD8bright+ cytotoxic effector T lymphocytes lacking
      CD28 expression.

PMID- 11978775
TI  - Autoantibodies to heat shock protein 90 in the human natural antibody repertoire.
AB  - The present study demonstrates the presence of natural autoantibodies of the IgG
      isotype directed against heat shock protein 90 (HSP90). The binding properties of
      affinity-purified anti-HSP antibodies were compared with those of natural
      antibodies specific for other self antigens, including anti-thyroglobulin and
      anti-myoglobin autoantibodies, by using semiquantitative immunoblotting, with
      solubilized proteins from normal liver tissue as antigens, and cross-blot
      analysis using purified self proteins. Affinity-purified anti-HSP90 antibodies
      were polyreactive and the non-HSP90-specific fraction of normal IgG was depleted
      in its natural autoantibody content. We further observed that self antigens
      including HSP, myosin, tubulin and aldolase with highly conserved structures show
      similar patterns of binding with natural antibodies, and form a well-defined
      cluster as demonstrated by cluster analysis of immunoreactivity data, whereas the
      less-conserved self and non-self antigens remained unclustered. The results favor
      the hypothesis that HSP90 belongs to a subset of highly conserved and
      immunodominant self antigens that are the primary target for natural
      autoantibodies in normal human IgG.

PMID- 11978776
TI  - Glucocorticoid (GC) sensitivity and GC receptor expression differ in thymocyte
      subpopulations.
AB  - Positive and negative selection steps in the thymus prevent non-functional or
      harmful T cells from reaching the periphery. To examine the role of
      glucocorticoid (GC) hormone and its intracellular receptor (GCR) in thymocyte
      development we measured the GCR expression in different thymocyte subpopulations
      of BALB/c mice with or without previous dexamethasone (DX), anti-CD3 mAb, RU-486
      and RU-43044 treatment. Four-color labeling of thymocytes allowed detection of
      surface CD4/CD8/CD69 expression in parallel with intracellular GCR molecules by
      flow cytometry. Double-positive (DP) CD4+CD8+ thymocytes showed the lowest GCR
      expression compared to double-negative (DN) CD4-CD8- thymocytes and mature single
      positive (SP) cells. DX treatment caused a concentration-dependent depletion of
      the DP cell population and increased appearance of mature SP cells with reduced
      GCR levels. GCR antagonists (RU-486 or RU-43044) did not influence the effect of
      DX on thymocyte composition; however, RU-43044 inhibited the high-dose GC-induced
      GCR down-regulation in SP and DN cells. GCR antagonists alone did not influence
      the maturation of thymocytes and receptor numbers. Combined low-dose anti-CD3 mAb
      and DX treatment caused an enhanced maturation (positive selection) of thymocytes
      followed by the elevation of CD69+ DP cells. The sensitivity of DP thymocytes
      with a GCRlow phenotype to GC action and the ineffectiveness of the GCR
      antagonist treatment may reflect a non-genomic GC action in the thymic selection
      steps.

PMID- 11978778
TI  - MHC class II-deficient tumor cell lines with a defective expression of the class
      II transactivator.
AB  - MHC class II expression defects have been evidenced in several human tumor cell
      lines originating from lung cancers or retinoblastoma. Accordingly, the mouse
      adenocarcinoma and fibrosarcoma cell lines, RAG and L(tk-), do not express I-A
      and I-E molecules even when treated with IFN-gamma. Here we show that fusion of
      both cell lines restores the inducible expression of MHC class II, thereby
      demonstrating that they present different and recessive alterations outside the
      MHC class II locus. CIITA, the MHC class II transactivator, controls the tissue
      specific expression of MHC class II genes and creates the architecture of the
      transcriptional complex that binds to the MHC class II gene promoters. In L(tk-)
      cells, C2ta transcripts, expressed from the gene encoding CIITA, were indeed
      detected in severely limited amounts, with a defect in C2ta transcription
      initiation. In agreement we show here that the L(tk-) cell line does not express
      the CIITA protein. In contrast, in the RAG cell line, C2ta transcripts were
      expressed at normal levels, from the proper initiation site. The nucleotide
      sequencing of the CIITA cDNA from RAG did not reveal any mutation. However, the
      CIITA protein was not detected. These data evidence a new type of defect in a MHC
      class II-defective tumor cell line, as we show here that the alteration in the
      RAG cells occurs downstream of C2ta transcription. The RAG mutation might
      therefore reside in the C2ta transcript nuclear export or translation, or in the
      stability of the CIITA protein.

PMID- 11978777
TI  - Functional modulation of expanded CD8+ synovial fluid T cells by NK cell receptor
      expression in HLA-B27-associated reactive arthritis.
AB  - The aim of this study was to determine whether NK cell receptor (NKR) expression
      could modulate cytotoxicity of oligoclonal CD8+ T cells present in the synovial
      fluid (SF) of HLA-B27-reactive arthritis (ReA) patients, especially in a TCRBV1
      population shared among different patients and cytotoxic toward HLA-B27. A CD8+ T
      cell line, two TCRBV1 lines and clones were isolated from the SF of an HLA-B27+
      ReA patient, and tested with mAb specific for Ig-like (KIR2DL1, KIR2DL2, KIR3DL1
      and ILT2) and CD94 C-type lectin NKR. Transcripts for NKG2 subunits (NKG2A-2E)
      associated with CD94 were also evaluated. Function was tested in a 51Cr-release
      cytotoxic assay. We found stable but distinct levels of CD94/NKG2 complexes at
      the surface of T cell lines and clones. Different NKG2 members could be
      associated with CD94, either inhibitory (NKG2A/B) or activating (NKG2C). The
      inhibitory ILT2 receptor could also be differently expressed, but other Ig-like
      NKR were negative. Functionally, one TCRBV1 line and clones with a high
      CD94/NKG2A expression did not lyse B27+ targets. Another TCRBV1 line with the
      same TCRBV1 rearrangement had a low expression of CD94/NKG2A, but expressed NKG2C
      transcripts and was cytotoxic toward HLA-B27. HLA-B27 is a ligand for ILT2 and we
      observed an inhibitory effect of ILT2 engagement on B*2705 targets in blockade
      experiments. Altogether, these data indicate a high degree of heterogeneity in
      the expression of NKR by intrasynovial CD8+ T cells which could modulate their
      cytotoxicity and play a role in the control of this HLA class I-associated
      autoimmune disease.

PMID- 11978779
TI  - Soluble proteins and haptens on bone marrow-derived dendritic cells are presented
      to host CD4 T cells in an MHC-restricted manner.
AB  - Because of their potent antigen-presenting capacity, dendritic cells (DC) have
      been used extensively in immunotherapy protocols. Our purpose was to functionally
      characterize mouse bone marrow-derived DC (BMDC) in vitro (in protein antigen-
      and hapten-specific assays) and in vivo (injecting soluble protein- and hapten
      pulsed DC) to determine their suitability for the generation of T(h) cell
      responses. Furthermore, we determined whether there is cross-presentation on MHC
      class II molecules during in vivo protein and hapten sensitization. Co-culture of
      protein-pulsed [with hen egg lysozyme (HEL) or with pigeon cytochrome c (CYT)] DC
      with T cells from HEL- or CYT- sensitized mice induced antigen-specific T cell
      proliferation, but compared to cultured Langerhans cells (LC), BMDC required
      higher protein antigen-pulsing concentrations (100 microg and 1 mg/ml). In
      contrast, at low protein concentrations (10 microg/ml), BMDC stimulated an HEL
      specific hybridoma very efficiently. Using an in vitro T cell proliferation assay
      and in vivo delayed-type hypersensitivity and contact sensitivity assays, we
      found that protein- and hapten-pulsed BMDC were able to sensitize syngeneic but
      not allogeneic hosts. Furthermore, if we injected BALB/c- and C57BL/6-derived HEL
      pulsed BMDC into F1 mice, specific secondary proliferation of primed T cells
      occurred only when antigen-pulsed stimulator cells syngeneic to the injected BMDC
      were used. Using this model system we found that soluble proteins and haptens are
      presented by injected BMDC to host T cells in an MHC-restricted manner in vivo.

PMID- 11978780
TI  - IL-18-independent cytotoxic T lymphocyte activation and IFN-gamma production
      during experimental acute graft-versus-host disease.
AB  - Acute graft-versus-host disease (GvHD) is a serious complication after allogeneic
      bone marrow transplantation. Donor-derived T cells infiltrate recipient target
      organs and cause severe tissue damage, often leading to death of the affected
      patient. Tissue destruction is a direct result of donor CD8+ T cell activation
      and cell-mediated cytotoxicity. IL-18 is a novel pro-inflammatory cytokine with
      potent T(h)1 immune response-promoting and cytotoxic T lymphocyte (CTL)-inducing
      activity. IL-18 is strongly induced in experimental mouse models and human
      patients with acute GvHD. However, the precise role of IL-18 in the development
      of acute GvHD is still unknown. In this study, we have used IL-18-binding
      protein, a soluble IL-18 decoy receptor, to specifically neutralize IL-18 in vivo
      and in vitro. Our results demonstrate that IL-18 is induced during GvHD. However,
      its effect in the induction of GvHD appears to be redundant, since neutralization
      of IL-18 does not alter any disease parameter analyzed. Our study further shows
      that IFN-gamma production and CTL induction upon activation by T cell mitogens or
      by alloantigen does not involve IL-18-mediated amplification, in contrast to
      lipopolysaccharide-induced IFN-gamma production. We conclude that IL-18
      expression correlates with the course of GvHD; however, its effect is dispensable
      for IFN-gamma and CTL induction for the initiation phase of this disease, most
      likely due to direct, IL-18-independent, CTL activation.

PMID- 11978781
TI  - Critical role of CD81 in cognate T-B cell interactions leading to Th2 responses.
AB  - We previously demonstrated that CD81-/- mice fail to develop Th2-biased immune
      responses and allergen-induced airway hyper-reactivity. Because CD81 is expressed
      on both activated T and on B cells, we examined the role of CD81 expression by
      each cell type. We established an in vitro system by backcrossing the CD81
      deletion to TCR transgenic (Tg) mice and to BCR Tg mice. Here we demonstrate that
      CD81 expression by T cells is critical for their induction of IL-4 synthesis by B
      cells. CD81-/- TCR Tg T cells were impaired in IL-4 production compared to
      CD81+/+ TCR Tg T cells, whereas CD81-/- and CD81+/+ BCR Tg B cells induced
      equivalent amounts of IL-4 in CD81+/+ TCR Tg T cells. CD81-/- TCR Tg T cells
      expressed reduced levels of ICOS, GATA-3, STAT6 and phosphorylated STAT6 when
      activated by antigen-presenting B cells. Taken together, these results indicate
      that CD81 expression by T cells greatly enhances cognate T-B cell interactions
      and greatly augments intracellular activation pathways leading to Th2
      polarization.

PMID- 11978782
TI  - Memorizing innate instructions requires a sufficiently specific adaptive immune
      system.
AB  - During its primary encounter with a pathogen, the immune system has to decide
      which type of immune response is most appropriate. Based on signals from the
      innate immune system and the immunological context in which the pathogen is
      presented, responding lymphocytes will adopt a particular phenotype, e.g. secrete
      a particular profile of cytokines. Once stimulated, lymphocytes store the
      appropriate type of response by differentiating from a naive to a memory
      phenotype. This allows the appropriate type of immune reaction to be regenerated
      upon re-stimulation of those memory clones. We developed a computer simulation
      model in which cross-reacting effector/memory clones contribute to the
      immunological context of pathogens. If a pathogen is recognized by both naive
      clones and pre-existing effector/memory clones, the naive lymphocytes adopt the
      effector mechanism of the memory clone. The adaptive immune system thereby stores
      immunological decisions and somatically learns to induce the right type of immune
      response to pathogens sharing epitopes. The influence of effector/memory
      lymphocytes may be detrimental when they cross-react to new pathogens that
      require a different kind of immune response. Here, we show that the immune system
      needs to be sufficiently specific to avoid such mistakes and to profit from the
      information that is stored in effector/memory lymphocytes. Repertoire diversity
      is required to reconcile this specificity with reactivity against many pathogens.

PMID- 11978783
TI  - HLA-B27 misfolding is associated with aberrant intermolecular disulfide bond
      formation (dimerization) in the endoplasmic reticulum.
AB  - The class I protein HLA-B27 confers susceptibility to inflammatory arthritis in
      humans and when overexpressed in rodents for reasons that remain unclear. We
      demonstrated previously that HLA-B27 heavy chains (HC) undergo endoplasmic
      reticulum (ER)-associated degradation. We report here that HLA-B27 HC also forms
      two types of aberrant disulfide-linked complexes (dimers) during the folding and
      assembly process that can be distinguished by conformation-sensitive antibodies
      W6/32 and HC10. HC10-reactive dimers form immediately after HC synthesis in the
      ER and constitute at least 25% of the HC pool, whereas W6/32-reactive dimers
      appear several hours later and represent less than 10% of the folded HC. HC10
      reactive dimers accumulate in the absence of tapasin or beta(2)-microglobulin,
      whereas W6/32-reactive dimers are not detected. Efficient formation of W6/32
      reactive dimers appears to depend on the transporter associated with antigen
      processing, tapasin, and beta(2)-microglobulin. The unpaired Cys(67) and residues
      at the base of the B pocket that dramatically impair HLA-B27 HC folding are
      critical for the formation of HC10-reactive ER dimers. Although certain other
      alleles also form dimers late in the assembly pathway, ER dimerization of HLA-B27
      may be unique. These results demonstrate that residues comprising the HLA-B27 B
      pocket result in aberrant HC folding and disulfide bond formation, and thus
      confer unusual properties on this molecule that are unrelated to peptide
      selection per se, yet may be important in disease pathogenesis.

PMID- 11978784
TI  - Inhibition of deactivation of NO-sensitive guanylyl cyclase accounts for the
      sensitizing effect of YC-1.
AB  - Many of the physiological effects of the signaling molecule nitric oxide are
      mediated by the stimulation of the NO-sensitive guanylyl cyclase. Activation of
      the enzyme is achieved by binding of NO to the prosthetic heme group of the
      enzyme and the initiation of conformational changes. So far, the rate of NO
      dissociation of the purified enzyme has only been determined
      spectrophotometrically, whereas the respective deactivation, i.e. the decline in
      enzymatic activity, has only been determined in cytosolic fractions and intact
      cells. Here, we report on the deactivation of purified NO-sensitive guanylyl
      cyclase determined after addition of the NO scavenger oxyhemoglobin or dilution.
      The deactivation rate corresponded to a half-life of the NO/guanylyl cyclase
      complex of approximately 4 s, which is in good agreement with the
      spectrophotometrically measured NO dissociation rate of the enzyme. The
      deactivation rate of the enzyme determined in platelets yielded a much shorter
      half-life indicating either partial damage of the enzyme during the purification
      procedure or the existence of endogenous deactivation accelerating factors. YC-1,
      a component causing sensitization of guanylyl cyclase toward NO, inhibited
      deactivation of guanylyl cyclase, resulting in an extremely prolonged half-life
      of the NO/guanylyl cyclase complex of more than 10 min. The deactivation of an
      ATP-utilizing guanylyl cyclase mutant was almost unaffected by YC-1, indicating
      the existence of a special structure within the catalytic domain required for YC
      1 binding or for the transduction of the YC-1 effect. In contrast to the wild
      type enzyme, YC-1 did not increase NO sensitivity of this mutant, clearly
      establishing inhibition of deactivation as the underlying mechanism of the NO
      sensitizer YC-1.

PMID- 11978785
TI  - Contribution of macrophage migration inhibitory factor to extracellular signal
      regulated kinase activation by oxidative stress in cardiomyocytes.
AB  - In response to oxidative stress, the pathogenesis of a number of cardiovascular
      events and several genes are stimulated by extracellular signal-regulated kinases
      (ERK1/2). Biphasic (early, 10 min; and delayed, 120 min) ERK1/2 activation by
      H(2)O(2), a reactive oxygen species, was observed in cultured neonatal rat
      cardiomyocytes. We investigated the hypothesis that the delayed activation of
      ERK1/2 depends on a factor secreted by oxidative stress (FSO). The delayed
      activation was inhibited by calphostin C, a protein kinase C inhibitor.
      Conditioned medium (CM) obtained from cells stimulated with H(2)O(2) induced
      rapid and monophasic ERK1/2 activation, which was not inhibited by calphostin C.
      In contrast, calphostin C-pretreated CM did not activate ERK1/2. Macrophage
      migration inhibitory factor (MIF) was one of the candidate FSOs activating
      ERK1/2. The existence of MIF in CM, the recombinant MIF-stimulated ERK1/2 rapid
      activation, and anti-MIF neutralizing antibody-induced inhibition of the delayed
      activation implied that MIF could be the FSO. Pretreatment of cardiomyocytes with
      a mitogen-activated protein kinase/ERK kinase (MEK) inhibitor did not suppress
      the MIF secretion, although it prevented the ERK1/2 activation by H(2)O(2). These
      results indicate that MIF is secreted from cardiomyocytes as a result of
      oxidative stress and activates ERK1/2 through a MEK1/2-dependent mechanism,
      although the secretion is not regulated by ERK1/2 but by protein kinase C.

PMID- 11978786
TI  - Identification of biologically active chemokine isoforms from ascitic fluid and
      elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian
      carcinoma.
AB  - Chemokines are important in leukocyte homeostasis, inflammation, angiogenesis,
      and metastasis. Here, the molecular diversity of chemokines present in ovarian
      carcinoma was studied by purifying the proteins to homogeneity from ascitic
      fluid. Biologically active intact CCL2 and processed CXCL8, CCL3, and CCL18
      isoforms were recovered. CCL7 and CCL20 were also purified, but their levels were
      10-fold lower compared with CXCL8, CCL2, and CCL3 and even 100-fold lower than
      the amounts of CCL18 isolated. In ascitic fluids from patients with ovarian
      carcinoma (n = 12), significantly higher levels of CXCL8 and CCL18 (2.0 versus
      0.7 ng/ml (p = 0.01) and 120 versus 44 ng/ml (p = 0.0002), respectively) were
      detected compared with those in nonovarian carcinoma patients (n = 12). In
      contrast to CXCL8, CCL18 was not inducible in carcinoma cell lines.
      Immunostaining showed CCL18 expression in tumor-infiltrating cells with
      monocyte/macrophage morphology but not in the ovarian carcinoma cells. Our data
      demonstrate that biochemically heterogenous but biologically active forms of
      several chemokines are present at different concentrations in ovarian carcinoma
      ascitic fluid. This points to a delicate balance of chemokines in epithelial
      ovarian cancer and to a potentially major role for CXCL8 and CCL18 in this tumor.

PMID- 11978787
TI  - Activation of polycyclic aromatic hydrocarbon trans-dihydrodiol proximate
      carcinogens by human aldo-keto reductase (AKR1C) enzymes and their functional
      overexpression in human lung carcinoma (A549) cells.
AB  - Polycyclic aromatic hydrocarbons (PAH) are environmental pollutants and suspected
      human lung carcinogens. In patients with non-small cell lung carcinoma,
      differential display shows that aldo-keto reductase (AKR1C) transcripts are
      dramatically overexpressed. However, whether AKR1C isoforms contribute to the
      carcinogenic process and oxidize potent PAH trans-dihydrodiols (proximate
      carcinogens) to reactive and redox active o-quinones is unknown; nor is it known
      whether these reactions occur in human lungs. We now show that four homogeneous
      human recombinant aldo-keto reductases (AKR1C1-AKR1C4) are regioselective and
      oxidize only the relevant non-K region trans-dihydrodiols. However, these enzymes
      are not stereo-selective, since they oxidized 100% of these racemic substrates.
      The highest utilization ratios (V(max)/K(m)) were observed for some of the most
      potent proximate carcinogens known (e.g. 7,12-dimethylbenz[a]anthracene-3,4-diol
      (DMBA-3,4-diol) and benzo[g]chrysene-11,12-diol). In vitro, DMBA-3,4-diol was
      oxidized by AKR1C4 to the highly reactive 7,12-dimethylbenz[a]anthracene-3,4
      dione (DMBA-3,4-dione), which was trapped in situ as its mono- and bis-thioether
      conjugates, which arise from the sequential 1,6- and 1,4-Michael addition of
      thiol nucleophiles. Human multiple tissue expression array analysis showed that
      AKR1C isoform transcripts were highly expressed in the human lung carcinoma cell
      line A549. Isoform-specific reverse transcriptase-PCR showed that AKR1C1, AKR1C2,
      and AKR1C3 transcripts were all expressed. Western blot analysis and functional
      assays confirmed high expression of AKR1C protein and enzyme activity in these
      lung cells. A549 cell lysates were found to convert DMBA-3,4-diol to the
      corresponding o-quinone. In trapping experiments, LC/MS analysis identified peaks
      in the cell lysates that corresponded to the synthetically prepared mono- and bis
      thioether conjugates of DMBA-3,4-dione. This quinone is one of the most
      electrophilic and redox-active o-quinones produced by AKRs. Its unique ability to
      form bis-thioether conjugates parallels the formation of bis- and tris
      glutathionyl conjugates of hydroquinone, which display end organ toxicity. The
      ability to measure DMBA-3,4-dione formation in A549 cells implicates the AKR
      pathway in the metabolic activation of PAH in human lung.

PMID- 11978788
TI  - Activation of the ERK pathway and atypical protein kinase C isoforms in exercise-
      and aminoimidazole-4-carboxamide-1-beta-D-riboside (AICAR)-stimulated glucose
      transport.
AB  - Exercise increases glucose transport in muscle by activating 5'-AMP-activated
      protein kinase (AMPK), but subsequent events are unclear. Presently, we examined
      the possibility that AMPK increases glucose transport through atypical protein
      kinase Cs (aPKCs) by activating proline-rich tyrosine kinase-2 (PYK2), ERK
      pathway components, and phospholipase D (PLD). In mice, treadmill exercise
      rapidly activated ERK and aPKCs in mouse vastus lateralis muscles. In rat
      extensor digitorum longus (EDL) muscles, (a) AMPK activator, 5-aminoimidazole-4
      carboxamide-1-beta-d-riboside (AICAR), activated PYK2, ERK and aPKCs; (b) effects
      of AICAR on ERK and aPKCs were blocked by tyrosine kinase inhibitor, genistein,
      and MEK1 inhibitor, PD98059; and (c) effects of AICAR on aPKCs and 2-deoxyglucose
      (2-DOG) uptake were inhibited by genistein, PD98059, and PLD-inhibitor, 1
      butanol. Similarly, in L6 myotubes, (a) AICAR activated PYK2, ERK, PLD, and
      aPKCs; (b) effects of AICAR on ERK were inhibited by genistein, PD98059, and
      expression of dominant-negative PYK2; (c) effects of AICAR on PLD were inhibited
      by MEK1 inhibitor UO126; (d) effects of AICAR on aPKCs were inhibited by
      genistein, PD98059, 1-butanol, and expression of dominant-negative forms of PYK2,
      GRB2, SOS, RAS, RAF, and ERK; and (e) effects of AICAR on 2DOG uptake/GLUT4
      translocation were inhibited by genistein, PD98059, UO126, 1-butanol, cell
      permeable myristoylated PKC-zeta pseudosubstrate, and expression of kinase
      inactive RAF, ERK, and PKC-zeta. AMPK activator dinitrophenol had effects on ERK,
      aPKCs, and 2-DOG uptake similar to those of AICAR. Our findings suggest that
      effects of exercise on glucose transport that are dependent on AMPK are mediated
      via PYK2, the ERK pathway, PLD, and aPKCs.

PMID- 11978789
TI  - Glucagon-like peptide-2 receptor activation engages bad and glycogen synthase
      kinase-3 in a protein kinase A-dependent manner and prevents apoptosis following
      inhibition of phosphatidylinositol 3-kinase.
AB  - Activation of glucagon-like peptide-2 receptor (GLP-2R) signaling promotes
      expansion of the mucosal epithelium indirectly via activation of growth and anti
      apoptotic pathways; however, the cellular mechanisms coupling direct GLP-2R
      activation to cell survival remain poorly understood. We now demonstrate that GLP
      2, in a cycloheximide-insensitive manner, enhanced survival in baby hamster
      kidney cells stably transfected with the rat GLP-2R; reduced mitochondrial
      cytochrome c efflux; and attenuated the caspase-dependent cleavage of Akt,
      poly(ADP-ribose) polymerase, and beta-catenin following inhibition of
      phosphatidylinositol 3-kinase (PI3K) by LY294002. The prosurvival effects of GLP
      2 on LY294002-induced cell death were independent of Akt, p90(Rsk), or p70 S6
      kinase activation; were mimicked by forskolin; and were abrogated by inhibition
      of protein kinase A (PKA) activity. GLP-2 inhibited activation of glycogen
      synthase kinase-3 (GSK-3) through phosphorylation at Ser(21) in GSK-3alpha and at
      Ser(9) in GSK-3beta in a PI3K-independent, PKA-dependent manner. GLP-2 reduced
      LY294002-induced mitochondrial association of endogenous Bad and Bax and
      stimulated phosphorylation of a transfected Bad fusion protein at Ser(155) in a
      PI3K-independent, but H89-sensitive manner, a modification known to suppress Bad
      pro-apoptotic activity. These results suggest that GLP-2R signaling enhances cell
      survival independently of PI3K/Akt by inhibiting the activity of a subset of pro
      apoptotic downstream targets of Akt in a PKA-dependent manner.

PMID- 11978790
TI  - Bi-directional regulation of UV-induced activation of p38 kinase and c-Jun N
      terminal kinase by G protein beta gamma-subunits.
AB  - Ultraviolet (UV) irradiation induces various cellular responses by activating
      many UV-responsive enzymes including mitogen-activated protein kinases (MAPKs).
      Various G protein-coupled receptor agonists also activate MAPKs, but it is not
      known whether or not G proteins also mediate the UV-induced activation of MAPKs.
      Therefore, this study was undertaken to determine whether the G protein betagamma
      subunit (Gbetagamma) mediates the UV-induced activation of p38 and JNK.
      Gbetagamma overexpression in COS-1 cells amplified the UV-induced activation of
      p38 but reduced JNK activation. The overexpression of the C-terminal region of
      beta-adrenergic receptor kinase (betaARKct) decreased the UV-induced activation
      of p38 but increased JNK activation. Gbeta(1)gamma(2) expression increased MKK3/6
      phosphorylation with a concomitant decrease in MKK4 phosphorylation, which
      contrasts with betaARKct expression. Gbeta(1)gamma(2) or betaARKct expression
      resulted in corresponding changes in the transcriptional activity of CHOP and c
      Jun. Treatment with a p38 inhibitor, SB203580, or the expression of a kinase
      inactive p38 increased the UV-induced JNK activation. Expression of the
      constitutively active MKK6 decreased the UV-induced JNK activation. In summary,
      although the endogenous Gbetagamma was found to mediate about half of the UV
      induced activation of p38, it was found that exogenous Gbetagamma mediates the bi
      directional regulation of UV-induced p38 and JNK activation, and that this bi
      directional regulation results from the inhibition of JNK activation by the p38
      activated via Gbetagamma in the COS-1 cells.

PMID- 11978791
TI  - Vasoactive intestinal polypeptide type-1 receptor regulation. Desensitization,
      phosphorylation, and sequestration.
AB  - The vasoactive intestinal polypeptide type-1 (VPAC(1)) receptor is a class II G
      protein-coupled receptor, distinct from the adrenergic receptor superfamily. The
      mechanisms involved in the regulation of the VPAC(1) receptor are largely
      unknown. We examined agonist-dependent VPAC(1) receptor signaling,
      phosphorylation, desensitization, and sequestration in human embryonic kidney 293
      cells. Agonist stimulation of cells overexpressing this receptor led to a dose
      dependent increase in cAMP that peaked within 5-10 min and was completely
      desensitized after 20 min. Cells cotransfected with the VPAC(1) receptor
      (VPAC(1)R) and G protein-coupled receptor kinases (GRKs) 2, 3, 5, and 6 exhibited
      enhanced desensitization that was not evident with GRK 4. Immunoprecipitation of
      the epitope-tagged VPAC(1) receptor revealed dose-dependent phosphorylation that
      was increased with cotransfection of any GRK. Agonist-stimulated internalization
      of the VPAC(1)R peaked in 10 min, and neither overexpressed beta-arrestin nor its
      dominant-negative mutant altered internalization. However, a dynamin-dominant
      negative mutant did inhibit VPAC(1) receptor internalization. Interestingly,
      VPAC(1)R specificity in desensitization was not evident by study of the
      overexpressed receptor; however, we determined that human embryonic kidney 293
      cells express an endogenous VPAC(1)R that did demonstrate dose-dependent GRK
      specificity. Therefore, VPAC(1) receptor regulation involves agonist-stimulated,
      GRK-mediated phosphorylation, beta-arrestin translocation, and dynamin-dependent
      receptor internalization. Moreover, study of endogenously expressed receptors may
      provide information not evident in overexpressed systems.

PMID- 11978793
TI  - The FeMoco-deficient MoFe protein produced by a nifH deletion strain of
      Azotobacter vinelandii shows unusual P-cluster features.
AB  - The His-tag MoFe protein expressed by the nifH deletion strain Azotobacter
      vinelandii DJ1165 (Delta(nifH) MoFe protein) was purified in large quantity. The
      alpha(2)beta(2) tetrameric Delta(nifH) MoFe protein is FeMoco-deficient based on
      metal analysis and the absence of the S = 3/2 EPR signal, which arises from the
      FeMo cofactor center in wild-type MoFe protein. The Delta(nifH) MoFe protein
      contains 18.6 mol Fe/mol and, upon reduction with dithionite, exhibits an
      unusually strong S = 1/2 EPR signal in the g approximately 2 region. The indigo
      disulfonate-oxidized Delta(nifH) MoFe protein does not show features of the P(2+)
      state of the P-cluster of the Delta(nifB) MoFe protein. The oxidized Delta(nifH)
      MoFe protein is able to form a specific complex with the Fe protein containing
      the [4Fe-4S](1+) cluster and facilitates the hydrolysis of MgATP within this
      complex. However, it is not able to accept electrons from the [4Fe-4S](1+)
      cluster of the Fe protein. Furthermore, the dithionite-reduced Delta(nifH) MoFe
      can be further reduced by Ti(III) citrate, which is quite unexpected. These
      unusual catalytic and spectroscopic properties might indicate the presence of a P
      cluster precursor or a P-cluster trapped in an unusual conformation or oxidation
      state.

PMID- 11978792
TI  - Characterization of the human gene encoding the scavenger receptor expressed by
      endothelial cell and its regulation by a novel transcription factor, endothelial
      zinc finger protein-2.
AB  - The scavenger receptor expressed by endothelial cell (SREC), mediates the
      selective uptake of modified low density lipoprotein (LDL), such as acetylated
      LDL and oxidized LDL, into endothelial cells. The SREC gene spans 12 kilobase
      pairs and contains 11 exons. Analysis of full-length cDNA clones of SREC from a
      peripheral blood leukocyte cDNA library revealed that at least five alternatively
      spliced cDNAs were present, and two of them encoded soluble forms of SREC. The
      transcription start site of the SREC gene was mapped, and DNA sequence analysis
      revealed an Sp1 binding site in its proximal region. Deletion analysis of the 5'
      flanking sequence revealed that sequence between base pairs -108 and -98 was
      critical for the promoter activity. This region contained half of an inverted
      repeat (IR) sequence with a triple nucleotide spacer (IR-3). A protected sequence
      between base pairs -268 and +17 was defined by in vitro DNase I footprinting
      analysis using human umbilical vein endothelial cell (HUVEC) nuclear extract. A
      novel transcription factor, endothelial zinc finger protein-2 (EZF-2), that binds
      to the 5'-flanking critical region of the SREC promoter activity was cloned from
      a HUVEC cDNA library employing a one-hybrid system. Whereas purified recombinant
      Sp1 alone produced similar protection in in vitro DNase I footprinting analysis,
      EZF-2 also bound to the 5'-flanking region SREC promoter. Co-transfection of SREC
      promoter and Sp1 or EZF-2 expression plasmids in HUVEC revealed that EZF-2 but
      not Sp1 increased SREC promoter activity. On the other hand, the mutation of
      either the Sp1 motif or IR-3 motif resulted in a decrease in the promoter
      activity. These results suggest that whereas Sp1 is the major nuclear protein
      bound to the regulatory region of the promoter, both EZF-2 and Sp1 are
      responsible for its regulation.

PMID- 11978794
TI  - The oncoprotein Set/TAF-1beta, an inhibitor of histone acetyltransferase,
      inhibits active demethylation of DNA, integrating DNA methylation and
      transcriptional silencing.
AB  - Histone hypoacetylation and DNA hypermethylation are hallmarks of gene silencing.
      Although a role for DNA methylation in regulating histone acetylation has been
      established, it is not clear how and whether epigenetic histone markings
      influence DNA modifications in transcriptional silencing. We have previously
      shown that induction of histone acetylation by trichostatin A promotes
      demethylation of ectopically methylated DNA (Cervoni, N., and Szyf, M. (2001) J.
      Biol. Chem. 276, 40778-40787). The oncoprotein Set/TAF-Ibeta is a subunit of the
      recently identified inhibitor of acetyltransferases complex that inhibits histone
      acetylation by binding to and masking histone acetyltransferase targets (Seo, S.
      B., McNamara, P., Heo, S., Turner, A., Lane, W. S., and Chakravarti, D. (2001)
      Cell 104, 119-130). We show here that the overexpression of Set/TAF-Ibeta, whose
      expression is up-regulated in multiple tumor tissues, inhibits demethylation of
      ectopically methylated DNA resulting in gene silencing. Overexpression of a
      mutant Set/TAF-Ibeta that does not inhibit histone acetylation is defective in
      inhibiting DNA demethylation. Taken together, these results are consistent with a
      novel regulatory role for Set/TAF-Ibeta, integrating epigenetic states of
      histones and DNA in gene regulation and provide a new mechanism that can explain
      how hypermethylation of specific regions might come about by inhibition of
      demethylation in cancer cells.

PMID- 11978795
TI  - Ras signaling enhances the activity of C/EBP alpha to induce granulocytic
      differentiation by phosphorylation of serine 248.
AB  - The transcription factor C/EBP alpha regulates early steps of normal granulocyte
      differentiation since mice with a disruption of the C/EBP alpha gene do not
      express detectable levels of the granulocyte colony-stimulating factor receptor
      and produce no neutrophils. We have recently shown that C/EBP alpha function is
      also impaired in acute myeloid leukemias. However, how the transcriptional
      activity of C/EBP alpha is regulated both in myelopoiesis and leukemogenesis is
      not fully understood. The current study demonstrates that activated Ras enhances
      the ability of C/EBP alpha to transactivate the granulocyte colony-stimulating
      factor receptor promoter and a minimal promoter containing only C/EBP DNA binding
      sites. Ras signaling activates C/EBP alpha via the transactivation domain because
      it enhances the transactivation function of a fusion protein containing a Gal4
      DNA binding domain and the C/EBP alpha transactivation domain and does not change
      C/EBP alpha DNA binding. Ras acts on serine 248 of the C/EBP alpha
      transactivation domain, because it does not enhance the transactivation function
      of a C/EBP alpha serine 248 to alanine point mutant. Interestingly, serine 248 of
      C/EBP alpha is a protein kinase C (PKC) consensus site, and a PKC inhibitor
      blocks the activation of C/EB alpha by Ras. Ras signaling leads to
      phosphorylation of C/EBP alpha in vivo. Finally, mutation of serine 248 to
      alanine obviates the ability of C/EBP alpha to induce granulocytic
      differentiation. These data suggest a model where Ras signaling enhances the
      activity of C/EBP alpha to induce granulocytic differentiation by phosphorylation
      of serine 248.

PMID- 11978796
TI  - Identification and quantification of major maillard cross-links in human serum
      albumin and lens protein. Evidence for glucosepane as the dominant compound.
AB  - Glycation reactions leading to protein modifications (advanced glycation end
      products) contribute to various pathologies associated with the general aging
      process and long term complications of diabetes. However, only few relevant
      compounds have so far been detected in vivo. We now report on the first
      unequivocal identification of the lysine-arginine cross-links glucosepane 5,
      DOGDIC 6, MODIC 7, and GODIC 8 in human material. For their accurate
      quantification by coupled liquid chromatography-electrospray ionization mass
      spectrometry, (13)C-labeled reference compounds were synthesized independently.
      Compounds 5-8 are formed via the alpha-dicarbonyl compounds N(6)-(2,3-dihydroxy
      5,6-dioxohexyl)-l-lysinate (1a,b), 3-deoxyglucosone (), methylglyoxal (), and
      glyoxal (), respectively. The protein-bound dideoxyosone 1a,b seems to be of
      prime significance for cross-linking because it presumably is not detoxified by
      mammalian enzymes as readily as 2-4. Hence, the follow-up product glucosepane 5
      was found to be the dominant compound. Up to 42.3 pmol of 5/mg of protein was
      identified in human serum albumin of diabetics; the level of 5 correlates
      markedly with the glycated hemoglobin HbA(1c). In the water-insoluble fraction of
      lens proteins from normoglycemics, concentration of 5 ranges between 132.3 and
      241.7 pmol/mg. The advanced glycoxidation end product GODIC 8 is elevated
      significantly in brunescent lenses, indicating enhanced oxidative stress in this
      material. Compounds 5-8 thus appear predestined as markers for pathophysiological
      processes.

PMID- 11978797
TI  - Identification of a novel transporter for dicarboxylates and tricarboxylates in
      plant mitochondria. Bacterial expression, reconstitution, functional
      characterization, and tissue distribution.
AB  - A cDNA from Arabidopsis thaliana and four related cDNAs from Nicotiana tabacum
      that we have isolated encode hitherto unidentified members of the mitochondrial
      carrier family. These proteins have been overexpressed in bacteria and
      reconstituted into phospholipid vesicles. Their transport properties demonstrate
      that they are orthologs/isoforms of a novel mitochondrial carrier capable of
      transporting both dicarboxylates (such as malate, oxaloacetate, oxoglutarate, and
      maleate) and tricarboxylates (such as citrate, isocitrate, cis-aconitate, and
      trans-aconitate). The newly identified dicarboxylate-tricarboxylate carrier
      accepts only the single protonated form of citrate (H-citrate2-) and the
      unprotonated form of malate (malate2-) and catalyzes obligatory, electroneutral
      exchanges. Oxoglutarate, citrate, and malate are mutually competitive inhibitors,
      showing K(i) close to the respective K(m). The carrier is expressed in all plant
      tissues examined and is largely spread in the plant kingdom. Furthermore, nitrate
      supply to nitrogen-starved tobacco plants leads to an increase in its mRNA in
      roots and leaves. The dicarboxylate-tricarboxylate carrier may play a role in
      important plant metabolic functions requiring organic acid flux to or from the
      mitochondria, such as nitrogen assimilation, export of reducing equivalents from
      the mitochondria, and fatty acid elongation.

PMID- 11978798
TI  - A novel pathway for nickel-induced interleukin-8 expression.
AB  - Inhalation of particulate nickel subsulfide (Ni3S2) causes chronic active
      inflammation and fibrosis of the lungs. However, the mechanisms for these effects
      are not well understood. Therefore, cell culture experiments with BEAS-2B human
      airway epithelial cells were conducted to test the hypothesis that exposure to
      non-cytotoxic levels of Ni3S2 induces expression of inflammatory cytokines such
      as interleukin-8 (IL-8). Exposure to Ni3S2 for 48 h was required to significantly
      increase IL-8 protein levels. Transcriptional stimulation of IL-8 mRNA levels
      preceded the increase in protein. Transient exposure to soluble nickel sulfate
      failed to increase IL-8 mRNA. Transfection with truncated IL-8 promoter
      constructs linked to the luciferase gene demonstrated that nickel-induced IL-8
      transcription required -272 bp of the promoter relative to the transcriptional
      start site. A -133-bp construct, containing cytokine and hypoxia-sensitive AP-1,
      NF-IL6, and NF-kappaB sites, was insufficient for induction by nickel.
      Transfection with a dominant negative AP-1 construct or mutation of the AP-1,
      GATA, or C/EBP sites in the -272-bp IL-8 promoter construct blocked induction by
      nickel. Inhibiting ERK, phosphatidylinositol 3-kinase, but not p38 kinase,
      diacylglycerol kinase, or hypoxia-inducible factor-1alpha, attenuated nickel
      induction of IL-8. These studies indicate that nickel induced IL-8 transcription
      through a novel pathway that requires both AP-1 and non-traditional transcription
      factors.

PMID- 11978799
TI  - Ca2+-dependent dephosphorylation of kinesin heavy chain on beta-granules in
      pancreatic beta-cells. Implications for regulated beta-granule transport and
      insulin exocytosis.
AB  - The specific biochemical steps required for glucose-regulated insulin exocytosis
      from beta-cells are not well defined. Elevation of glucose leads to increases in
      cytosolic [Ca2+]i and biphasic release of insulin from both a readily releasable
      and a storage pool of beta-granules. The effect of elevated [Ca2+]i on
      phosphorylation of isolated beta-granule membrane proteins was evaluated, and the
      phosphorylation of four proteins was found to be altered by [Ca2+]i. One (a 18/20
      kDa doublet) was a Ca2+-dependent increase in phosphorylation, and, surprisingly,
      three others (138, 42, and 36 kDa) were Ca2+-dependent dephosphorylations. The
      138-kDa beta-granule phosphoprotein was found to be kinesin heavy chain (KHC). At
      low levels of [Ca2+]i KHC was phosphorylated by casein kinase 2, but KHC was
      rapidly dephosphorylated by protein phosphatase 2B beta (PP2Bbeta) as [Ca2+]i
      increased. Inhibitors of PP2B specifically reduced the second, microtubule
      dependent, phase of insulin secretion, suggesting that dephosphorylation of KHC
      was required for transport of beta-granules from the storage pool to replenish
      the readily releasable pool of beta-granules. This is distinct from synaptic
      vesicle exocytosis, because neurotransmitter release from synaptosomes did not
      require a Ca2+-dependent KHC dephosphorylation. These results suggest a novel
      mechanism for regulating KHC function and beta-granule transport in beta-cells
      that is mediated by casein kinase 2 and PP2B. They also implicate a novel
      regulatory role for PP2B/calcineurin in the control of insulin secretion
      downstream of a rise in [Ca2+]i.

PMID- 11978800
TI  - Recombinant CLIC1 (NCC27) assembles in lipid bilayers via a pH-dependent two
      state process to form chloride ion channels with identical characteristics to
      those observed in Chinese hamster ovary cells expressing CLIC1.
AB  - CLIC1 (NCC27) is an unusual, largely intracellular, ion channel that exists in
      both soluble and membrane-associated forms. The soluble recombinant protein can
      be expressed in Escherichia coli, a property that has made possible both detailed
      electrophysiological studies in lipid bilayers and an examination of the
      mechanism of membrane integration. Soluble E. coli-derived CLIC1 moves from
      solution into artificial bilayers and forms chloride-selective ion channels with
      essentially identical conductance, pharmacology, and opening and closing kinetics
      to those observed in CLIC1-transfected Chinese hamster ovary cells. The process
      of membrane integration of CLIC1 is pH-dependent. Following addition of protein
      to the trans solution, small conductance channels with slow kinetics (SCSK)
      appear in the bilayer. These SCSK modules then appear to undergo a transition to
      form a high conductance channel with fast kinetics. This has four times the
      conductance of the SCSK and fast kinetics that characterize the native channel.
      This suggests that the CLIC1 ion channel is likely to consist of a tetrameric
      assembly of subunits and indicates that despite its size and unusual properties,
      it is able to form a completely functional ion channel in the absence of any
      other ancillary proteins.

PMID- 11978801
TI  - Induction of tissue factor expression in human endothelial cells by CD40 ligand
      is mediated via activator protein 1, nuclear factor kappa B, and Egr-1.
AB  - Induction of tissue factor expression in endothelial cells via ligation of CD40
      probably figures prominently in the pathogenesis of prevalent inflammatory
      diseases, including atherosclerosis. However, the molecular mechanisms of tissue
      factor gene expression triggered by CD40 ligand (CD40L) in this cell type remain
      unknown. We demonstrate here that the tissue factor promoter region -278 bp to
      +121 bp contains the CD40L-responsive elements, consisting of activator protein 1
      (AP-1)+/-, nuclear factor (NF) kappaB-, and Egr-1-binding sites. Mutations of
      either the AP-1- or NF-kappaB-binding sites markedly reduced the CD40L-dependent
      promoter activation. The AP-1 and NF-kappaB sites displayed constitutive and
      CD40L-enhanceable DNA binding activity, respectively. Of note, mutation of the
      Egr-1-binding sites, previously not associated with CD40 signaling, impaired
      activation of the tissue factor promoter. Accordingly, CD40L strongly induced Egr
      1 protein expression and DNA binding activity to all three bindings sites. In
      contrast to CD40L, other established inducers of tissue factor in endothelial
      cells, interleukin-1beta or tumor necrosis factor alpha, did not increase the
      expression of Egr-1. In conclusion, induction of tissue factor gene expression in
      human endothelial cells by CD40L involves AP-1 and NF-kappaB as well as Egr-1, a
      pathway previously not implicated in CD40 signaling and distinct from that
      employed by certain other proinflammatory cytokines.

PMID- 11978802
TI  - The amino-acid minimum for maintenance and growth, as exemplified by further
      experiments with lysine and tryptophane (Osborne, T. B., and Mendel, L. B. (1916)
      J. Biol. Chem. 25, 1-12) and The role of vitamines in the diet (Osborne, T. B.,
      and Mendel, L. B. (1917) J. Biol. Chem. 31, 149-163).

PMID- 11978803
TI  - A behavioral/systems approach to the neuroscience of drug addiction.

PMID- 11978804
TI  - The neuroscience of natural rewards: relevance to addictive drugs.

PMID- 11978805
TI  - Psychomotor stimulant addiction: a neural systems perspective.

PMID- 11978806
TI  - Neural systems underlying opiate addiction.

PMID- 11978807
TI  - Cannabinoid addiction: behavioral models and neural correlates.
AB  - The use of cannabis sativa preparations as recreational drugs can be traced back
      to the earliest civilizations. However, animal models of cannabinoid addiction
      allowing the exploration of neural correlates of cannabinoid abuse have been
      developed only recently. We review these models and the role of the CB1
      cannabinoid receptor, the main target of natural cannabinoids, and its
      interaction with opioid and dopamine transmission in reward circuits. Extensive
      reviews on the molecular basis of cannabinoid action are available elsewhere
      (Piomelli et al., 2000; Schlicker and Kathmann, 2001).

PMID- 11978808
TI  - Behavioral neurobiology of alcohol addiction: recent advances and challenges.
AB  - Addictive behavior associated with alcoholism is characterized by compulsive
      preoccupation with obtaining alcohol, loss of control over consumption, and
      development of tolerance and dependence, as well as impaired social and
      occupational functioning. Like other addictive disorders, alcoholism is
      characterized by chronic vulnerability to relapse after cessation of drinking. To
      understand the factors that compel some individuals to drink excessively, alcohol
      research has focused on the identification of brain mechanisms that support the
      reinforcing actions of alcohol and the progression of changes in neural function
      induced by chronic ethanol consumption that lead to the development of
      dependence. More recently, increasing attention has been directed toward the
      understanding of neurobiological and environmental factors in susceptibility to
      relapse.

PMID- 11978809
TI  - Neuronal systems underlying behaviors related to nicotine addiction: neural
      circuits and molecular genetics.
AB  - Nicotine addiction is a complex behavioral phenomenon comprising effects on
      several neural systems. Recent studies have expanded initial observations that
      the actions of nicotine on dopaminergic systems increase dopaminergic activity
      and release, leading to nicotine-induced reinforcement. Indeed, the actions of
      nicotine on many systems, including brainstem cholinergic, GABAergic,
      noradrenergic, and serotonergic nuclei, may help to mediate nicotine effects
      related to addiction. Furthermore, studies of mice lacking nicotinic
      acetylcholine receptor subunits or expressing supersensitive forms of these
      subunits have begun to tie together the molecular, neurochemical, and behavioral
      effects of nicotine. The use of multiple techniques by many laboratories provides
      optimism that the field is advancing toward elucidating the basic mechanisms of
      nicotine dependence.

PMID- 11978810
TI  - Regulation of exocytosis through Ca2+/ATP-dependent binding of autophosphorylated
      Ca2+/calmodulin-activated protein kinase II to syntaxin 1A.
AB  - Syntaxin 1A/HPC-1 is a key component of the exocytotic molecular machinery,
      namely, the soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP)
      receptor mechanism. Although >10 syntaxin-binding proteins have been identified,
      they cannot completely explain the regulation of exocytosis. Thus, novel proteins
      may interact with syntaxin. Because exocytosis requires both Ca2+ and ATP, we
      searched for Ca2+/ATP-dependent syntaxin-binding proteins from the rat brain and
      discovered Ca2+/calmodulin-activated protein kinase II (CaMKII)-alpha. At Ca2+
      concentrations of >10(-6) m, only autophosphorylated CaMKII bound to syntaxin.
      Bound CaMKII was released from syntaxin by EGTA or by phosphatase, indicating
      that the binding is reversible. CaMKII bound to the linker domain of syntaxin,
      unlike any other known syntaxin-binding proteins. CaMKII-syntaxin complexes were
      also detected in synaptosomes by immunoprecipitation, and when reconstituted in
      vitro, they recruited larger amounts of synaptotagmin and SNAP-25 than syntaxin
      alone. The microinjected CaMKII-binding domain of syntaxin specifically affected
      exocytosis in chromaffin cells and in neurons. These results indicate that the
      Ca2+/ATP-dependent binding of CaMKII to syntaxin is an important process in the
      regulation of exocytosis.

PMID- 11978811
TI  - Tissue plasminogen activator mediates microglial activation via its finger domain
      through annexin II.
AB  - Microglia are the immunocompetent cells of the CNS, and their activation is
      thought to play an important neurotoxic role in many diseases modeled by
      glutamate-induced excitotoxicity. One molecule whose expression is upregulated
      after excitotoxic injury is tissue plasminogen activator (tPA), a serine protease
      with dual roles in the CNS. The catalytic activity of tPA, which converts
      plasminogen into plasmin, leads to neuronal death during excitotoxicity. Via a
      nonproteolytic mechanism, tPA also mediates microglial activation. We show here
      in culture studies that stimulated wild-type neurons and microglia can release
      the tPA that elicits the activation, and that tPA acts in combination with other
      factors. We also show that the finger domain of tPA is necessary to trigger the
      activation and identify annexin II as its probable binding partner-receptor.
      Together, these findings suggest that tPA released by either neurons or microglia
      can act as a neural cytokine, signaling through annexin II to activate microglia
      in settings of disease and injury. Developing methods to inhibit the interaction
      of tPA with annexin II would offer a new and selective approach to interfere with
      microglial activation for therapeutic purposes.

PMID- 11978812
TI  - Phosphatidylinositol 3-kinase is required for the expression but not for the
      induction or the maintenance of long-term potentiation in the hippocampal CA1
      region.
AB  - Several signal transduction pathways have been implicated in the induction of
      long-term potentiation (LTP), yet the signal transduction mechanisms behind the
      maintenance-expression phase of LTP are still poorly understood. We investigated
      the role of phosphatidylinositol 3-kinase (PI3-kinase) in LTP at Schaffer
      collateral/commissural fiber-CA1 synapses in rat hippocampal slices using
      biochemical approaches and extracellular electrophysiological recordings. We
      observed that PI3-kinase activity was induced in the CA1 region during LTP of
      field EPSPs (fEPSPs) and that two structurally unrelated PI3-kinase inhibitors,
      LY294002 and wortmannin, abated established LTP, suggesting that PI3-kinase is
      involved in the maintenance-expression phase of LTP. However, LTP recovered after
      washout of the reversible PI3-kinase inhibitor LY294002, confirming that LTP
      maintenance and expression are distinct events and indicating that PI3-kinase
      activity is required for LTP expression rather than for its maintenance.
      Interestingly, preincubation with LY294002 did not prevent LTP induction. In
      fact, if LY294002 was withdrawn 5 min after high-frequency stimulation, an LTP of
      fEPSP was seen. Last, a voltage-dependent calcium channel-dependent form of LTP
      in the CA1 could also be reversibly abated by LY294002, raising the possibility
      that PI3-kinase could be required for the expression of multiple forms of
      synaptic potentiation.

PMID- 11978813
TI  - 3beta -hydroxypregnane steroids are pregnenolone sulfate-like GABA(A) receptor
      antagonists.
AB  - Endogenous neurosteroids have rapid actions on ion channels, particularly GABA(A)
      receptors, which are potentiated by nanomolar concentrations of 3alpha
      hydroxypregnane neurosteroids. Previous evidence suggests that 3beta
      hydroxypregnane steroids may competitively antagonize potentiation induced by
      their 3alpha diastereomers. Because of the potential importance of antagonists as
      experimental and clinical tools, we characterized the functional effect of 3beta
      hydroxysteroids. Although 3beta-hydroxysteroids reduced the potentiation induced
      by 3alpha-hydroxysteroids, 3beta-hydroxysteroids acted noncompetitively with
      respect to potentiating steroids and inhibited the largest degrees of
      potentiation most effectively. Potentiation by high concentrations of
      barbiturates was also reduced by 3beta-hydroxysteroids. 3beta-Hydroxysteroids are
      also direct, noncompetitive GABA(A) receptor antagonists. 3beta-Hydroxysteroids
      coapplied with GABA significantly inhibited responses to > or =15 microm GABA.
      The profile of block was similar to that exhibited by sulfated steroids, known
      blockers of GABA(A) receptors. This direct, noncompetitive effect of 3beta
      hydroxysteroids was sufficient to account for the apparent antagonism of
      potentiating steroids. Mutated receptors exhibiting decreased sensitivity to
      sulfated steroid block were insensitive to both the direct effects of 3beta
      hydroxysteroids on GABA(A) responses and the reduction of potentiating steroid
      effects. At concentrations that had little effect on GABAergic synaptic currents,
      3beta-hydroxysteroids and low concentrations of sulfated steroids significantly
      reversed the potentiation of synaptic currents induced by 3alpha-hydroxysteroids.
      We conclude that 3beta-hydroxypregnane steroids are not direct antagonists of
      potentiating steroids but rather are noncompetitive, likely state-dependent,
      blockers of GABA(A) receptors. Nevertheless, these steroids may be useful
      functional blockers of potentiating steroids when used at concentrations that do
      not affect baseline neurotransmission.

PMID- 11978814
TI  - Activation of c-Jun N-terminal kinase and p38 in an Alzheimer's disease model is
      associated with amyloid deposition.
AB  - The mechanisms by which neurons and synapses are lost in Alzheimer's disease (AD)
      are not completely understood. To characterize potential signaling events linked
      to AD pathogenesis, activation-specific antibodies were used to examine mitogen
      activated protein kinase (MAPK) kinase pathways at various ages in mice
      transgenic for human amyloid precursor protein-695 with the Swedish familial AD
      mutations (Tg2576) and homozygous for a P264L familial AD mutation introduced by
      targeting of the presenilin-1 gene (PS1(P264L)). Although the c-Jun N-terminal
      kinase (JNK) and p38 pathways were significantly activated in the cortex at both
      7 and 12 months of age, there was no significant activation of the extracellular
      signal-regulated kinase pathway. MAPK kinase-4, an upstream activator of JNK, was
      also significantly activated at 7 and 12 months, whereas c-Jun, a downstream
      effector of JNK-associated apoptotic signaling, was not induced. The lack of c
      Jun activation is consistent with the absence of neuronal loss in both cortex and
      hippocampal CA1 at 12 months. The JNK activation was localized to amyloid
      deposits, within neurites containing phosphorylated tau. Synaptophysin was
      quantified biochemically as a measure of synaptic integrity and was significantly
      reduced in an age-dependent manner in the Tg2576/PS1(P264L) cortex but not in
      either PS1(P264L) or Tg2576 cortex. Stress-responsive MAP kinase pathways were
      activated in the brain of the Tg2576/PS1(P264L) AD model, and this activation was
      coincident with the age-dependent increase in amyloid deposition, tau
      phosphorylation, and loss of synaptophysin.

PMID- 11978815
TI  - Hydrogen sulfide is produced in response to neuronal excitation.
AB  - Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous
      gas, it is endogenously produced in the brain. Physiological concentrations of
      H2S selectively enhance NMDA receptor-mediated responses and alter the induction
      of hippocampal long-term potentiation (LTP). Here we use cystathionine beta
      synthase (CBS) knock-out mice to clearly show that CBS produces endogenous H2S in
      the brain and that H2S production is greatly enhanced by the excitatory
      neurotransmitter l-glutamate, as well as by electrical stimulation. This
      increased CBS activity is regulated by a pathway involving Ca2+/calmodulin. In
      addition, LTP is altered in CBS knock-out mice. These observations suggest that
      H2S is produced by CBS in response to neuronal excitation and that it may
      regulate some aspects of synaptic activity.

PMID- 11978816
TI  - Functional stoichiometry of glutamate receptor desensitization.
AB  - Potassium (K+) channels and ionotropic glutamate receptors (iGluRs) fulfill
      divergent roles in vertebrate nervous systems. Despite this, however, recent work
      suggests that these ion channels are structurally homologous, sharing an
      ancestral protein, architectural design, and tetrameric subunit stoichiometry.
      Their gating mechanisms also are speculated to have overlapping features. Here we
      show that the mechanism of iGluR desensitization is unique. Unlike K+ channels,
      AMPA- and kainate-type iGluR subunits desensitize in several ordered
      conformational steps. AMPA receptors operate as dimers, whereas the functional
      stoichiometry of kainate receptor desensitization is dependent on external ions.
      Contrary to conventional understanding, kinetic models suggest that partially
      desensitized AMPA and kainate receptors conduct ions and are likely participants
      in synaptic signaling. Although sharing many structural correlates with K+
      channels, iGluRs have evolved unique subunit-subunit interactions, tailoring
      their gating behavior to fulfill distinct roles in neuronal signaling.

PMID- 11978817
TI  - Selective coupling of T-type calcium channels to SK potassium channels prevents
      intrinsic bursting in dopaminergic midbrain neurons.
AB  - Dopaminergic midbrain (DA) neurons display two principal activity patterns in
      vivo, single-spike and burst firing, the latter coding for reward-related events.
      We have shown recently that the small-conductance calcium-activated potassium
      channel SK3 controls pacemaker frequency and precision in DA neurons of the
      substantia nigra (SN), and previous studies have implicated SK channels in the
      transition to burst firing. To identify the upstream calcium sources for SK
      channel activation in DA SN neurons, we studied the sensitivity of SK channel
      mediated afterhyperpolarization (AHP) currents to inhibitors of different types
      of voltage-gated calcium channels in perforated patch-clamp recordings. Cobalt
      sensitive AHP currents were not affected by L-type and P/Q-type calcium channel
      inhibitors and were reduced slightly (26%) by the N-type channel inhibitor omega
      conotoxin-GVIA. In contrast, AHP currents were blocked substantially (85-94%) by
      micromolar concentrations of nickel (IC50, 33.75 microm) and mibefradil (IC50,
      4.83 microm), indistinguishable from the nickel and mibefradil sensitivities of T
      type calcium currents (IC50 values, 33.86 and 4.59 microm, respectively). These
      results indicate that SK channels are activated selectively via T-type calcium
      channels in DA SN neurons. Consequently, SK currents displayed use-dependent
      inactivation with similar time constants when compared with those of T-type
      calcium currents and generated a transient rebound inhibition. Both SK and T-type
      channels were essential for the stability of spontaneous pacemaker activity, and,
      in some DA SN neurons, T-type channel inhibition was sufficient to induce
      intrinsic burst firing. The functional coupling of SK to T-type channels has
      important implications for the temporal integration of synaptic input and might
      help to understand how DA neurons switch between pacemaker and burst-firing modes
      in vivo.

PMID- 11978818
TI  - Isolation of a long-lasting eag-related gene-type K+ current in MMQ lactotrophs
      and its accommodating role during slow firing and prolactin release.
AB  - Native rat lactotrophs express thyrotrophin-releasing hormone-dependent K+
      currents consisting of fast and slow deactivating components that are both
      sensitive to the class III anti-arrhythmic drugs that block the eag-related gene
      (ERG) K+ current (I(ERG)). Here we describe in MMQ prolactin-releasing pituitary
      cells the isolation of the slowly deactivating long-lasting component (I(ERGS)),
      which, unlike the fast component (I(ERGF)), is insensitive to verapamil 2 microm
      but sensitive to a novel scorpion toxin (ErgTx-2) that hardly affects I(ERGF).
      The time constants of I(ERGS) activation, deactivation, and recovery from
      inactivation are more than one order of magnitude greater than in I(ERGF), and
      the voltage-dependent inactivation is left-shifted by approximately 25 mV. The
      very slow MMQ firing frequency (approximately 0.2 Hz) investigated in perforated
      patch is increased approximately four times by anti-arrhythmic agents, by ErgTx
      2, and by the abrupt I(ERGS) deactivation. Prolactin secretion in the presence of
      anti-arrhythmics is three- to fourfold higher in comparison with controls. We
      provide evidence from I(ERGS) and I(ERGF) simulations in a firing model cell to
      indicate that only I(ERGS) has an accommodating role during the experimentally
      observed very slow firing. Thus, we suggest that I(ERGS) potently modulates both
      firing and prolactin release in lactotroph cells.

PMID- 11978819
TI  - Ca2+-independent feedback inhibition of acetylcholine release in frog
      neuromuscular junction.
AB  - The effect of membrane potential on feedback inhibition of acetylcholine (ACh)
      release was studied using the frog neuromuscular junction. It was found that
      membrane potential affects the functional affinity (K(i)) of the presynaptic M2
      muscarinic receptor. The K(i) for muscarine shifts from approximately 0.23 microm
      (at resting potential) to approximately 8 microm (at a high depolarization).
      Measurements of Ca2+ currents in axon terminals showed that the depolarization
      mediated shift in K(i) does not stem from depolarization-dependent changes in
      Ca2+ influx. Pretreatments with pertussis toxin (PTX) abolished the
      depolarization-dependent shift in K(i); at all depolarizations K(i) was the same
      and higher (approximately 32 microm) than before PTX treatment. The inhibitory
      effect of muscarine on ACh release is produced by two independent mechanisms: a
      slow, PTX-sensitive process, which prevails at low to medium depolarizations and
      operates already at low muscarine concentrations, and a fast, PTX-insensitive and
      voltage-independent process, which requires higher muscarine concentrations.
      Neither of the two processes involves a reduction in Ca2+ influx.

PMID- 11978820
TI  - Long-term depression induced by postsynaptic group II metabotropic glutamate
      receptors linked to phospholipase C and intracellular calcium rises in rat
      prefrontal cortex.
AB  - We have previously shown (Otani et al., 1999b) that bath application of
      (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV), the agonist of group
      II metabotropic glutamate receptors (mGluRs), induces postsynaptic Ca2+-dependent
      long-term depression (LTD) of layer I-II to layer V pyramidal neuron
      glutamatergic synapses of rat medial prefrontal cortex. In the present study, we
      examined detailed mechanisms of this DCG IV-induced LTD. First, the group II
      mGluR antagonist (RS)-alpha-methylserine-O-phosphate monophenyl ester blocked DCG
      IV-induced LTD, and another group II agonist (2S,3S,4S)-CCG/(2S,1'S,2'S)-2
      (carboxycyclopropyl)glycine-induced LTD, suggesting that LTD is indeed mediated
      by the activation of group II mGluRs. Second, DCG IV-induced LTD was blocked by
      the NMDA receptor antagonist AP-5, whereas DCG IV did not potentiate NMDA
      receptor-mediated synaptic responses. Interruption of single test stimuli during
      DCG IV application blocked DCG IV-induced LTD. These results suggest that small
      NMDA receptor-mediated responses evoked by single synaptic stimuli contribute to
      DCG IV-induced LTD. Third, DCG IV-induced LTD was blocked or reduced by the
      following drugs: phospholipase C inhibitor U-73122 (bath-applied or
      postsynaptically injected), postsynaptically injected IP3 receptor blocker
      heparin, phospholipase D-linked mGluR blocker PCCG-13, PKC inhibitor RO318220,
      postsynaptically injected PKC inhibitor PKC(19-36), and PKA inhibitor KT-5720.
      Fourth, fluorescent Ca2+ analysis techniques revealed that DCG IV increases Ca2+
      concentration in prefrontal layer V pyramidal neurons. These Ca2+ rises and the
      LTD were both blocked by postsynaptic heparin in the same cells. Taken together,
      these results suggest that postsynaptic group II mGluRs, linked to phospholipase
      C and probably also phospholipase D, induce LTD through postsynaptic PKC
      activation and IP3 receptor-mediated postsynaptic increases of Ca2+
      concentration.

PMID- 11978821
TI  - Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and
      corrects hippocampal long-term potentiation but not a cognitive defect of amyloid
      precursor protein [V717I] transgenic mice.
AB  - In the brain of Alzheimer's disease (AD) patients, neurotoxic amyloid peptides
      accumulate and are deposited as senile plaques. A major therapeutic strategy aims
      to decrease production of amyloid peptides by inhibition of gamma-secretase.
      Presenilins are polytopic transmembrane proteins that are essential for gamma
      secretase activity during development and in amyloid production. By loxP/Cre
      recombinase-mediated deletion, we generated mice with postnatal, neuron-specific
      presenilin-1 (PS1) deficiency, denoted PS1(n-/-), that were viable and fertile,
      with normal brain morphology. In adult PS1(n-/-) mice, levels of endogenous brain
      amyloid peptides were strongly decreased, concomitant with accumulation of
      amyloid precursor protein (APP) C-terminal fragments. In the cross of
      APP[V717I]xPS1 (n-/-) double transgenic mice, the neuronal absence of PS1
      effectively prevented amyloid pathology, even in mice that were 18 months old.
      This contrasted sharply with APP[V717I] single transgenic mice that all develop
      amyloid pathology at the age of 10-12 months. In APP[V717I]xPS1 (n-/-) mice, long
      term potentiation (LTP) was practically rescued at the end of the 2 hr
      observation period, again contrasting sharply with the strongly impaired LTP in
      APP[V717I] mice. The findings demonstrate the critical involvement of amyloid
      peptides in defective LTP in APP transgenic mice. Although these data open
      perspectives for therapy of AD by gamma-secretase inhibition, the neuronal
      absence of PS1 failed to rescue the cognitive defect, assessed by the object
      recognition test, of the parent APP[V717I] transgenic mice. This points to
      potentially detrimental effects of accumulating APP C99 fragments and demands
      further study of the consequences of inhibition of gamma-secretase activity. In
      addition, our data highlight the complex functional relation of APP and PS1 to
      cognition and neuronal plasticity in adult and aging brain.

PMID- 11978822
TI  - Nuclear calcium signaling evoked by cholinergic stimulation in hippocampal CA1
      pyramidal neurons.
AB  - The cholinergic system is thought to play an important role in hippocampal
      dependent learning and memory. However, the mechanism of action of the
      cholinergic system in these actions in not well understood. Here we examined the
      effect of muscarinic receptor stimulation in hippocampal CA1 pyramidal neurons
      using whole-cell recordings in acute brain slices coupled with high-speed imaging
      of intracellular calcium. Activation of muscarinic acetylcholine receptors by
      synaptic stimulation of cholinergic afferents or application of muscarinic
      agonist in CA1 pyramidal neurons evoked a focal rise in free calcium in the
      apical dendrite that propagated as a wave into the soma and invaded the nucleus.
      The calcium rise to a single action potential was reduced during muscarinic
      stimulation. Conversely, the calcium rise during trains of action potentials was
      enhanced during muscarinic stimulation. The enhancement of free intracellular
      calcium was most pronounced in the soma and nuclear regions. In many cases, the
      calcium rise was distinguished by a clear inflection in the rising phase of the
      calcium transient, indicative of a regenerative response. Both calcium waves and
      the amplification of action potential-induced calcium transients were blocked the
      emptying of intracellular calcium stores or by antagonism of inositol 1,4,5
      trisphosphate receptors with heparin or caffeine. Ryanodine receptors were not
      essential for the calcium waves or enhancement of calcium responses. Because
      rises in nuclear calcium are known to initiate the transcription of novel genes,
      we suggest that these actions of cholinergic stimulation may underlie its effects
      on learning and memory.

PMID- 11978823
TI  - Defective proboscis extension response (DPR), a member of the Ig superfamily
      required for the gustatory response to salt.
AB  - Gustatory stimuli, such as sugar, induce a behavioral response in Drosophila that
      involves extension of the proboscis and consumption of the sugar-containing
      solution. Addition of salt to the sugar solution inhibits this behavioral
      response. However, the mechanisms and gene products involved in the salt aversion
      response have not been described. Here, we report the identification of a locus,
      defective proboscis extension response (dpr), that is required for salt aversion.
      dpr was expressed in a subset of primary neurons in the gustatory organs and
      encoded a protein with two Ig-like domains, a single putative transmembrane
      domain, and a short region C terminal to the transmembrane segment. In addition,
      DPR defines a large previously unknown group of > or =20 highly related Ig
      containing proteins.

PMID- 11978824
TI  - Lentiviral-mediated delivery of mutant huntingtin in the striatum of rats induces
      a selective neuropathology modulated by polyglutamine repeat size, huntingtin
      expression levels, and protein length.
AB  - A new strategy based on lentiviral-mediated delivery of mutant huntingtin (htt)
      was used to create a genetic model of Huntington's disease (HD) in rats and to
      assess the relative contribution of polyglutamine (CAG) repeat size, htt
      expression levels, and protein length on the onset and specificity of the
      pathology. Lentiviral vectors coding for the first 171, 853, and 1520 amino acids
      of wild-type (19 CAG) or mutant htt (44, 66, and 82 CAG) driven by either the
      phosphoglycerate kinase 1 (PGK) or the cytomegalovirus (CMV) promoters were
      injected in rat striatum. A progressive pathology characterized by sequential
      appearance of ubiquitinated htt aggregates, loss of dopamine- and cAMP-regulated
      phosphoprotein of 32 kDa staining, and cell death was observed over 6 months with
      mutant htt. Earlier onset and more severe pathology occurred with shorter
      fragments, longer CAG repeats, and higher expression levels. Interestingly, the
      aggregates were predominantly located in the nucleus of PGK-htt171-injected rats,
      whereas they were present in both the nucleus and processes of CMV-htt171
      injected animals expressing lower transgene levels. Finally, a selective sparing
      of interneurons was observed in animals injected with vectors expressing mutant
      htt. These data demonstrate that lentiviral-mediated expression of mutant htt
      provides a robust in vivo genetic model for selective neural degeneration that
      will facilitate future studies on the pathogenesis of cell death and experimental
      therapeutics for HD.

PMID- 11978825
TI  - Peroxynitrite mediates neurotoxicity of amyloid beta-peptide1-42- and
      lipopolysaccharide-activated microglia.
AB  - The amyloid beta-peptide (Abeta) activates microglia and promotes the generation
      of cytokines and oxygen species, including nitric oxide (NO) and tumor necrosis
      factor alpha (TNF-alpha), which can be either neurotoxic or neuroprotective. We
      show that neuron death in cocultures of rat cortical microglia and neurons
      activated by lipopolysaccharide (LPS) or Abeta1-42 plus interferon gamma
      (IFNgamma) is caused by short-lived diffusible molecules and follows the
      generation of superoxide and/or peroxynitrite as determined by electron
      paramagnetic spectroscopy. Neurotoxicity induced by LPS or Abeta1-42 plus
      IFNgamma is blocked by inhibitors of NO synthesis and by the peroxynitrite (ONOO
      ) decomposition catalysts FeTMPyP [5,10,15,20-tetrakis(n-methyl-4'
      pyridyl)porphinato iron (III) chloride] and FeTPPS [5,10,15,20-tetrakis(4
      sulfonatophenyl)prophyrinato iron (III) chloride] but not by the TNF-alpha
      inhibitor pentoxifylline. The specificity of FeTMPyP for ONOO- was confirmed by
      its ability to block the toxicity of a peroxynitrite donor but not of NO donors
      or of high levels of superoxide in a yeast mutant lacking superoxide dismutase 1.
      These results implicate peroxynitrite as a mediator of the toxicity of activated
      microglia, which may play a major role in Abeta1-42 neurotoxicity and Alzheimer's
      disease.

PMID- 11978826
TI  - Differential palmitoylation directs the AMPA receptor-binding protein ABP to
      spines or to intracellular clusters.
AB  - Long-term changes in excitatory synapse strength are thought to reflect changes
      in synaptic abundance of AMPA receptors mediated by receptor trafficking. AMPA
      receptor-binding protein (ABP) and glutamate receptor-interacting protein (GRIP)
      are two similar PDZ (postsynaptic density 95/Discs large/zona occludens 1)
      proteins that interact with glutamate receptors 2 and 3 (GluR2 and GluR3)
      subunits. Both proteins have proposed roles during long-term potentiation and
      long-term depression in the delivery and anchorage of AMPA receptors at synapses.
      Here we report a variant of ABP-L (seven PDZ form of ABP) called pABP-L that is
      palmitoylated at a cysteine residue at position 11 within a novel 18 amino acid N
      terminal leader sequence encoded through differential splicing. In cultured
      hippocampal neurons, nonpalmitoylated ABP-L localizes with internal GluR2 pools
      expressed from a Sindbis virus vector, whereas pABP-L is membrane targeted and
      associates with surface-localized GluR2 receptors at the plasma membrane in
      spines. Mutation of Cys-11 to alanine blocks the palmitoylation of pABP-L and
      targets the protein to intracellular clusters, confirming that targeting the
      protein to spines is dependent on palmitoylation. Non-palmitoylated GRIP is
      primarily intracellular, but a chimera with the pABP-L N-terminal palmitoylation
      sequence linked to the body of the GRIP protein is targeted to spines. We suggest
      that pABP-L and ABP-L provide, respectively, synaptic and intracellular sites for
      the anchorage of AMPA receptors during receptor trafficking to and from the
      synapse.

PMID- 11978828
TI  - Muscle spindle-derived neurotrophin 3 regulates synaptic connectivity between
      muscle sensory and motor neurons.
AB  - Ia afferents induce the formation of muscle spindles prenatally and maintain them
      postnatally. To address whether spindles, in turn, regulate the function of Ia
      afferents, we examined Egr3-null mutant mice (Egr3-/-), in which muscle spindles
      degenerate progressively after birth. Egr3-/- mice develop gait ataxia,
      scoliosis, resting tremors, and ptosis, suggesting a defect in proprioception.
      Despite the normal morphological appearance of peripheral and central sensory
      projections, we observed a profound functional deficit in the strength of sensory
      motor connections in Egr3-/- mice. Muscle spindles in Egr3-/- mice do not express
      NT3. Intramuscular injections of NT3 to Egr3-/- mice during the postnatal period
      restored sensory-motor connections. Thus, NT3 derived from muscle spindles
      regulates the synaptic connectivity between muscle sensory and motor neurons.

PMID- 11978827
TI  - Upregulation of the Fas receptor death-inducing signaling complex after traumatic
      brain injury in mice and humans.
AB  - Recent studies have implicated Fas in the pathogenesis of inflammatory, ischemic,
      and traumatic brain injury (TBI); however, a direct link between Fas activation
      and caspase-mediated cell death has not been established in injured brain. We
      detected Fas-Fas ligand binding and assembly of death-inducing signaling
      complexes (DISCs) [Fas, Fas-associated protein with death domain, and procaspase
      8 or procaspase-10; receptor interacting protein (RIP)-RIP-associated interleukin
      1beta converting enzyme and CED-3 homolog-1/Ced 3 homologous protein with a death
      domain-procaspase-2] by immunoprecipitation and immunoblotting within mouse
      parietal cortex after controlled cortical impact. At the time of DISC assembly,
      procaspase-8 was cleaved and the cleavage product appeared at 48 hr in terminal
      deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive
      neurons. Cleavage of caspase-8 was accompanied by caspase-3 processing detected
      at 48 hr by immunohistochemistry, and by caspase-specific cleavage of poly(ADP
      ribose) polymerase at 12 hr. Fas pathways were also stimulated by TBI in human
      brain, because Fas expression plus Fas-procaspase-8 interaction were robust in
      contused cortical tissue samples surgically removed between 2 and 30 hr after
      injury. To address whether Fas functions as a death receptor in brain cells,
      cultured embryonic day 17 cortical neurons were transfected with an adenoviral
      vector containing the gene encoding Fas ligand. After 48 hr in culture, Fas
      ligand expression and Fas-procaspase-8 DISC assembly increased, and by 72 hr,
      cell death was pronounced. Cell death was decreased by approximately 50% after
      pan-caspase inhibition (Z-Val-ALa-Asp(Ome)-fluoromethylketone). These data
      suggest that Fas-associated DISCs assemble in neurons overexpressing Fas ligand
      as well as within mouse and human contused brain after TBI. Therefore, Fas may
      function as a death receptor after brain injury.

PMID- 11978829
TI  - Clonal architecture of the mouse hippocampus.
AB  - Experimental mouse chimeras have proven useful in analyzing the cell lineages of
      various tissues. Here we use experimental mouse chimeras to study cell lineage of
      the hippocampus. We examined clonal architecture and lineage relationships of the
      hippocampal pyramidal cells, dentate granule cells, and GABAergic interneurons.
      We quantitatively analyzed like-genotype cohorts of these neuronal populations in
      the hippocampus of the most highly skewed chimeras to provide estimates of the
      size of the progenitor pool that gives rise to these neuronal groups. We also
      compared the percentage chimerism across various brain structures to gain
      insights into the origins of the hippocampus relative to other neighboring
      regions of the brain. Our qualitative analyses demonstrate that like-genotype
      cohorts of pyramidal cells are aligned in radial arrays across the pyramidal cell
      layer, whereas like-genotype cohorts in the C-shaped dentate gyrus colonize
      either the outer shell or inner core of the granule cell layer in a symmetrical
      manner. Clonally related populations of GABAergic interneurons are dispersed
      throughout the hippocampus and originate from progenitors that are separate from
      either pyramidal or granule cells. Granule and pyramidal cells, however, are
      closely linked in their lineages. Our quantitative analyses yielded estimates of
      the size of the progenitor pools that establish the pyramidal, granule, and
      GABAergic interneuronal populations as consisting of 7000, 400, and 40
      progenitors, respectively, for each side of the hippocampus. Last, we found that
      the hippocampal pyramidal and granule cells share a lineage with cortical and
      diencephalic cells, pointing toward a common lineage that crosses the di
      telencephalic boundaries.

PMID- 11978830
TI  - Inhibition of protein kinase C prevents Purkinje cell death but does not affect
      axonal regeneration.
AB  - In organotypic cultures, mouse Purkinje cells regenerate their axons from
      embryonic day 18 (E18) to postnatal day 0 (P0), die of apoptosis between P1 and
      P7, and survive but do not regenerate at P10. This particular behavior of
      Purkinje cells did not allow us to find out when the developmental switch between
      regeneration and lack of regeneration occurs. This work was undertaken to
      suppress Purkinje cell apoptosis and to investigate whether the same molecules
      that prevent apoptosis could also influence axonal growth, regeneration, or both.
      We show that brain-derived neurotrophic factor, neurotrophin 3, and insulin-like
      growth factor I have marginal effects on P3 Purkinje cell death. The use of
      Go6976 [a protein kinase C (PKC) inhibitor] or a transgenic mouse line, in which
      a pseudosubstrate PKC inhibitor has been specifically targeted to Purkinje cells,
      prevents the massive Purkinje cell death in P3 organotypic cultures. In addition,
      Go6976 promotes axotomized Purkinje cell survival up to P7. Thus, the inhibition
      of PKC activity is able to prevent Purkinje cell apoptosis in organotypic
      cultures. Furthermore, Go6976 increases the outgrowth of dendrites and axon
      collateralization, as shown after gene gun enhanced green fluorescent protein
      transfection. In contrast, PKC inhibitors do not influence the axonal
      regenerative capability of Purkinje cell during development; the latter decreases
      between E18 and P7 after the same time course in control and Go6976-treated
      slices. Thus, because inhibition of PKC prevents Purkinje cell death but does not
      affect axonal regeneration, these two events (cell death and axonal regeneration)
      seem to be differentially regulated.

PMID- 11978831
TI  - GAP-43 is critical for normal development of the serotonergic innervation in
      forebrain.
AB  - Serotonergic (5-HT) axons from the raphe nuclei are among the earliest afferents
      to innervate the developing forebrain. The present study examined whether GAP-43,
      a growth-associated protein expressed on growing 5-HT axons, is necessary for
      normal 5-HT axonal outgrowth and terminal arborization during the perinatal
      period. We found a nearly complete failure of 5-HT immunoreactive axons to
      innervate the cortex and hippocampus in GAP-43-null (GAP43-/-) mice. Abnormal
      ingrowth of 5-HT axons was apparent on postnatal day 0 (P0); quantitative
      analysis of P7 brains revealed significant reductions in the density of 5-HT
      axons in the cortex and hippocampus of GAP43-/- mice relative to wild-type (WT)
      controls. In contrast, 5-HT axon density was normal in the striatum, septum, and
      amygdala and dramatically higher than normal in the thalamus of GAP43-/- mice.
      Concentrations of serotonin and its metabolite, 5-hydroxyindolacetic acid, and
      norepinephrine were decreased markedly in the anterior and posterior cerebrum but
      increased in the brainstem of GAP43-/- mice. Cell loss could not account for
      these abnormalities, because unbiased stereological analysis showed no
      significant difference in the number of 5-HT dorsal raphe neurons in P7 GAP43-/-
      versus WT mice. The aberrant 5-HT innervation pattern persisted at P21,
      indicating a long-term alteration of 5-HT projections to forebrain in the absence
      of GAP-43. In heterozygotes, the density and morphology of 5-HT axons was
      intermediate between WT and homozygous GAP43-/- mice. These results suggest that
      GAP-43 is a key regulator in normal pathfinding and arborization of 5-HT axons
      during early brain development.

PMID- 11978832
TI  - Patterns of Nogo mRNA and protein expression in the developing and adult rat and
      after CNS lesions.
AB  - Nogo-A is a neurite growth inhibitor involved in regenerative failure and
      restriction of structural plasticity in the adult CNS. Three major protein
      products (Nogo-A, -B, and -C) are derived from the nogo gene. Here we describe
      the embryonic and postnatal expression of the three Nogo isoforms in the rat by
      in situ hybridization and immunohistochemistry. Northern and Western blot
      analysis indicated that Nogo-A is predominantly expressed in the nervous system
      with lower levels also present in testis and heart. In CNS myelin, confocal and
      immunoelectron microscopy revealed that Nogo-A is expressed in oligodendrocyte
      cell bodies and processes and localized in the innermost adaxonal and outermost
      myelin membranes. Additionally, we find Nogo-A to be expressed by projection
      neurons, in particular during development, and by postmitotic cells in the
      developing cortex, spinal cord, and cerebellum. The expression levels of Nogo-A/B
      were not changed significantly after traumatic lesions to the cortex or spinal
      cord. Nogo-B showed widespread expression in the central and peripheral nervous
      systems and other peripheral tissues. Nogo-C was mainly found in skeletal muscle,
      but brain and heart were also found to express this isoform. The localization of
      Nogo-A in oligodendrocytes fits well with its role as a myelin-associated
      inhibitor of regenerative fiber growth and structural plasticity. However,
      expression of Nogo-A in other tissues and, in particular, in neurons and the
      widespread expression of the two shorter isoforms, Nogo-B and -C, suggest that
      the Nogo family of proteins might have function(s) additional to the neurite
      growth-inhibitory activity.

PMID- 11978833
TI  - Deleted in colorectal carcinoma and differentially expressed integrins mediate
      the directional migration of neural precursors in the rostral migratory stream.
AB  - Precursors of the olfactory interneurons migrate from the subventricular zone via
      the rostral migratory stream (RMS). To investigate the molecular mechanisms by
      which RMS cells migrate, we used a slice preparation, which allows the migrating
      cells to be imaged at very high temporal and spatial resolution in the presence
      of added inhibitors. Using immunohistochemistry, we first determined that the
      alpha1-, beta8-, and beta1-integrin subunits and the alpha5- and gamma1-laminin
      subunits are expressed during embryonic day 16 to the early postnatal stage.
      During early postnatal days, alpha(v)- and beta6-integrins appeared, and their
      expression persisted throughout adulthood. The migrating cells also expressed the
      netrin receptors neogenin and Deleted in Colorectal Carcinoma (DCC). Netrin-1 is
      expressed in olfactory mitral cells. Anti-integrin antibodies inhibited the
      production of protrusions as well as cellular translocation. In contrast, anti
      DCC antibodies primarily altered the direction of the protrusions; consequently,
      the migration was no longer unidirectional, and the speed was reduced. Thus, the
      interaction of DCC, possibly through an interaction with netrin-1, contributes to
      the direction of migration by regulating the formation of directed protrusions.
      In contrast, the integrins function in production of protrusions and cellular
      translocation, with different integrins participating at different developmental
      stages.

PMID- 11978834
TI  - A novel role for p75NTR in subplate growth cone complexity and visual
      thalamocortical innervation.
AB  - In cortical development, subplate axons pioneer the pathway from neocortex to the
      internal capsule, leading to the proposal that they are required for subsequent
      area-specific innervation of cortex by thalamic axons. A role for p75 neutrophin
      receptor (NTR) in area-specific thalamic innervation of cortex is suggested by
      the observation that p75NTR expression is restricted to subplate neurons in a low
      rostral to high-caudal gradient throughout the period of thalamocortical
      innervation. In vitro, neurotrophin 3 binding to p75NTR increases neurite length
      and filopodial formation of immunopurified subplate neurons, suggesting a role
      for p75NTR in subplate growth cone morphology and function in vivo. Consistent
      with this idea, subplate growth cones have markedly fewer filopodia in mice
      lacking p75NTR than in wild type mice. Despite this gross morphologic defect,
      many subplate axons in knock-out mice pioneer the projection to the internal
      capsule as they do in wild-type mice. However a few subplate axons in the knock
      out mice make ectopic projections rostral in the intermediate zone and frontal
      cortex. Concomitant with the altered morphology of subplate growth cones, mice
      lacking p75NTR have diminished innervation of visual cortex from the lateral
      geniculate nucleus, with markedly reduced or absent connections in 48% of knock
      out mice. Thalamic projections to auditory and somatosensory cortex are normal,
      consistent with the gradient of p75NTR expression. Our present results are
      unusual in that they argue that p75NTR functions in a novel way in subplate
      neurons, that is, in growth cone morphology and function rather than in axon
      extension or neuronal survival.

PMID- 11978835
TI  - Increased neurogenesis in adult mCD24-deficient mice.
AB  - mCD24, a glycosylphosphatidylinositol-anchored highly glycosylated molecule, is
      expressed on differentiating neurons during development. In the adult CNS, its
      expression is restricted to immature neurons located in two regions showing
      ongoing neurogenesis: the subventricular zone (SVZ) of the lateral ventricle
      pathway and the dentate gyrus (DG) of the hippocampal formation. Here, combining
      bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen labelings we
      confirmed that mCD24 is expressed on proliferating cells. To determine whether
      the inactivation of the molecule may affect adult neurogenesis, we analyzed the
      phenotype of mCD24-deficient mice (mCD24-/-). We labeled cells in S-phase with a
      pulse, a long, or a cumulative administration of BrdU and analyzed cells in
      different zones according to their dividing rate (rapid and slow) both in the
      control and mCD24-/-. We found a significant increase in the number of rapid (in
      the SVZ and the DG) and slow (in the SVZ) proliferating cells. Cumulative assays
      revealed a global reduction of the total cell cycle duration of rapidly
      proliferating precursors of SVZ. We investigated the fate of supernumerary cells
      and observed an increased number of apoptotic cells (terminal deoxynucleotidyl
      transferase-mediated biotinylated UTP nick end labeling) in the mutant SVZ.
      Furthermore, we found no difference in the size of the olfactory bulb between
      wild-type (WT) and mutant mice. In support, mCD24 deletion did not appear to
      affect migration in the migratory stream. A comparison of the organization of
      migrating precursors between WT and mCD24 -/-, both in vivo at the optic and
      electron microscopic levels and in SVZ cultured explants, did not show any
      changes in the arrangement of neuroblasts in chain-like structures. Altogether,
      our data suggest that mCD24 regulates negatively cell proliferation in zones of
      secondary neurogenesis.

PMID- 11978836
TI  - Estrogen and aging affect the subcellular distribution of estrogen receptor-alpha
      in the hippocampus of female rats.
AB  - Estrogen replacement increases both the number of dendritic spines and the
      density of axospinous synapses in the hippocampal CA1 region in young rats, yet
      this is attenuated in aged rats. The estrogen receptor-alpha (ER-alpha) is
      localized within select spines of CA1 pyramidal cells in young animals and thus
      may be involved locally in this process. The present study investigated the
      effects of estrogen on the ultrastructural distribution of ER-alpha in the CA1 of
      young (3-4 months) and aged (22-23 months) Sprague Dawley rats using
      postembedding immunogold electron microscopy. Within dendritic spines, most ER
      alpha immunoreactivity (IR) was seen in plasmalemmal and cytoplasmic regions of
      spine heads, with a smaller proportion within 60 nm of the postsynaptic density.
      In presynaptic terminals, ER-alpha-IR was clustered and often associated with
      synaptic vesicles. Significant effects of both aging and estrogen were observed.
      Quantitative analysis revealed that nonsynaptic pools of ER-alpha-IR within the
      presynaptic and postsynaptic compartments were decreased (35 and 27%,
      respectively) in the young estrogen-replaced animals compared with those that
      received vehicle. Such localized regulation of ER-alpha in response to
      circulating estrogen levels might directly affect synaptic signaling in CA1
      pyramidal cells. No estrogen treatment-related differences were observed in the
      aged animals. However, 50% fewer spines contained ER-alpha in the aged compared
      with young hippocampus. These data suggest that the decreased responsiveness of
      hippocampal synapses to estrogen in aged animals may result from age-related
      decrements in ER-alpha levels and its subcellular localization vis-a-vis the
      synapse. Such a role for spinous ER-alpha has important implications for age
      related attenuation of estrogen-induced hippocampal plasticity.

PMID- 11978837
TI  - Protein tyrosine phosphatase-mu differentially regulates neurite outgrowth of
      nasal and temporal neurons in the retina.
AB  - Cell adhesion molecules play an important role in the development of the visual
      system. The receptor-type protein tyrosine phosphatase, PTPmu is a cell adhesion
      molecule that mediates cell aggregation and may signal in response to adhesion.
      PTPmu is expressed in the chick retina during development and promotes neurite
      outgrowth from retinal ganglion cell (RGC) axons in vitro (Burden-Gulley and
      Brady-Kalnay, 1999). The axons of RGC neurons form the optic nerve, which is the
      sole output from the retina to the optic tectum in the chick. In this study, we
      observed that PTPmu expression in RGC axons occurs as a step gradient, with
      temporal axons expressing the highest level of PTPmu. PTPmu expression in the
      optic tectum occurred as a smooth descending gradient from anterior to posterior
      regions during development. Because temporal RGC axons innervate anterior tectal
      regions, PTPmu may regulate the formation of topographic projections to the
      tectum. In agreement with this hypothesis, a differential response of RGC
      neurites to a PTPmu substrate was also observed: RGCs of temporal retina were
      unable to extend neurites on PTPmu compared with neurites of nasal retina. When
      given a choice between PTPmu and a second substrate, the growth cones of temporal
      neurites clustered at the PTPmu border and stalled, thus avoiding additional
      growth on the PTPmu substrate. In contrast, PTPmu was permissive for growth of
      nasal neurites. Finally, application of soluble PTPmu to retinal cultures
      resulted in the collapse of temporal but not nasal growth cones. Therefore, PTPmu
      may specifically signal to temporal RGC axons to cease their forward growth after
      reaching the anterior tectum, thus allowing for subsequent innervation of deeper
      tectal layers.

PMID- 11978838
TI  - A hippocampal NR2B deficit can mimic age-related changes in long-term
      potentiation and spatial learning in the Fischer 344 rat.
AB  - Aged rats are known to have deficits in spatial learning behavior in the Morris
      water maze. We have found that aged rats also have deficits in NR2B protein
      expression and that the protein expression deficit is correlated with their
      performance in the Morris water maze. To test whether this NR2B deficit was
      sufficient to account for the behavioral deficit, we used antisense
      oligonucleotides to specifically knock down NR2B subunit expression in the
      hippocampus of young rats. NR2B antisense treatment diminished NMDA receptor
      responses, abolished NMDA-dependent long-term potentiation (LTP), and impaired
      spatial learning. These data demonstrate the important role of NR2B in LTP and
      learning and memory and suggest a role for reduced NR2B expression in age-related
      cognitive decline.

PMID- 11978839
TI  - Overcoming the effects of stress on synaptic plasticity in the intact
      hippocampus: rapid actions of serotonergic and antidepressant agents.
AB  - Acute inescapable stress dramatically affects the inducibility of plasticity at
      glutamatergic synapses in the intact hippocampus. The present study examined the
      involvement of serotonergic mechanisms in mediating and modulating the block of
      long-term potentiation (LTP) in the CA1 area of anesthetized rats after exposure
      to an elevated platform stress. Fluoxetine and fenfluramine, agents that raise
      hippocampal extracellular 5-HT concentration, blocked the induction of LTP in
      nonstressed animals, thus mimicking the effect of stress. In contrast, (+/-)
      tianeptine, a drug that decreases 5-HT levels, had no effect on LTP induction in
      nonstressed animals. Remarkably, (+/-) administration of tianeptine after the
      stress rapidly overcame the block of LTP induction without affecting baseline
      excitatory transmission. Consistent with a reduction of 5-HT levels being
      responsible for this effect of tianeptine, the (-) enantiomer, which is
      associated with the 5-HT uptake enhancing action of (+/-)-tianeptine, also caused
      a recovery of the induction of LTP in previously stressed animals, whereas the
      relatively inactive (+) enantiomer had no effect. Furthermore, fluoxetine
      prevented the effect of tianeptine in stressed animals. These findings show that
      antidepressants have rapid and powerful interactions with the mechanisms
      controlling the persistence of the block of LTP by inescapable stress.

PMID- 11978840
TI  - Upregulation of a T-type Ca2+ channel causes a long-lasting modification of
      neuronal firing mode after status epilepticus.
AB  - A single episode of status epilepticus (SE) causes numerous structural and
      functional changes in the brain that can lead to the development of a chronic
      epileptic condition. Most studies of this plasticity have focused on changes in
      excitatory and inhibitory synaptic properties. However, the intrinsic firing
      properties that shape the output of the neuron to a given synaptic input may also
      be persistently affected by SE. Thus, 54% of CA1 pyramidal cells, which normally
      fire in a regular mode, are persistently converted to a bursting mode after an
      episode of SE induced by the convulsant pilocarpine. In this model, intrinsic
      bursts evoked by threshold-straddling depolarizations, and their underlying spike
      afterdepolarizations (ADPs), were resistant to antagonists of N-, P/Q-, or L-type
      Ca2+ channels but were readily suppressed by low (30-100 microm) concentrations
      of Ni2+ known to block T- and R-type Ca2+ channels. The density of T-type Ca2+
      currents, but not of other pharmacologically isolated Ca2+ current types, was
      upregulated in CA1 pyramidal neurons after SE. The augmented T-type currents were
      sensitive to Ni2+ in the same concentration range that blocked the novel
      intrinsic bursting in these neurons (IC50 = 27 microm). These data suggest that
      SE may persistently convert regular firing cells to intrinsic bursters by
      selectively increasing the density of a Ni2+-sensitive T-type Ca2+ current. This
      nonsynaptic plasticity considerably amplifies the output of CA1 pyramidal neurons
      to synaptic inputs and most probably contributes to the development and
      expression of an epileptic condition after SE.

PMID- 11978841
TI  - Nicotine self-administration impairs hippocampal plasticity.
AB  - Nicotine, the neuroactive compound responsible for tobacco addiction, is
      primarily believed to have beneficial effects on the adult brain. However, in
      heavy smokers, abstinence from nicotine is accompanied by cognitive impairments
      that suggest adverse effects of nicotine on brain plasticity. For this reason, we
      studied changes in plasticity-related processes in the dentate gyrus (DG) of the
      hippocampal formation of animals trained to self-administer nicotine. The DG was
      chosen because it undergoes profound plastic rearrangements, many of which have
      been related to memory and learning performances. In this region, we examined the
      expression of the polysialylated (PSA) forms of neural cell adhesion molecule
      (NCAM), PSA-NCAM, neurogenesis, and cell death by measuring the number of
      pyknotic cells. It was found that nicotine self-administration profoundly
      decreased, in a dose-dependent manner, the expression of PSA-NCAM in the DG; a
      significant effect was observed at all the doses tested (0.02, 0.04, and 0.08
      mg/kg per infusion). Neurogenesis was also decreased in the DG, but a significant
      effect was observed only for the two highest doses of nicotine. Finally, the same
      doses that decreased neurogenesis also increased cell death. These results raise
      an important additional concern for the health consequences of nicotine abuse and
      open new insight on the possible neural mechanisms of tobacco addiction.

PMID- 11978842
TI  - Regional and cellular mapping of cAMP response element-mediated transcription
      during naltrexone-precipitated morphine withdrawal.
AB  - Chronic opiate exposure is associated with upregulation of the cAMP signaling
      pathway and the transcription factor cAMP response element-binding protein in the
      locus ceruleus (LC) and certain other brain areas. To determine whether these
      adaptations ultimately affect transcription mediated by the cAMP response element
      (CRE), we induced morphine dependence in CRE-LacZ transgenic mice and performed a
      regional and cellular mapping of beta-galactosidase (beta-gal) expression during
      naltrexone-precipitated withdrawal. Consistent with our model of opiate
      dependence, beta-gal expression increased in the LC, but decreased in the lateral
      ventral tegmental area (VTA) and dorsal raphe nucleus (DRN). In addition,
      withdrawal increased beta-gal expression in the continuum of the extended
      amygdala and nucleus accumbens, macrostructures associated with the coupling of
      emotional stimuli to motor and autonomic responses. At the cellular level, in the
      central nucleus of the amygdala, beta-gal was found in cells both with and
      without mu opioid receptors as well as in corticotropin-releasing factor
      expressing cells. In nucleus accumbens, beta-gal was expressed in several major
      subpopulations of neurons. In LC, beta-gal expression was induced predominantly
      in tyrosine hydroxylase-expressing cells, whereas in the VTA and DRN the majority
      of cells expressing beta-gal were nonmonoaminergic. These results show that
      molecular adaptations to chronic morphine alter CRE-mediated transcription during
      opiate withdrawal in physiologically salient regions involved in arousal, reward,
      mood, and affective responses. We propose that CRE-mediated transcription serves
      as a functional marker for neuronal plasticity during withdrawal. CRE-mediated
      transcription may itself contribute to re-establishing homeostasis in the
      organism through target gene regulation in these regions.

PMID- 11978843
TI  - Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP
      response element-binding protein.
AB  - The cAMP cascade, including the cAMP response element-binding protein (CREB), is
      known to play an important role in neuronal survival and plasticity. Here the
      influence of this cascade on neurogenesis in adult hippocampus was determined.
      Activation of the cAMP cascade by administration of rolipram, an inhibitor of
      cAMP breakdown, increased the proliferation of newborn cells in adult mouse
      hippocampus. In addition, rolipram induction of cell proliferation resulted in
      mature granule cells that express neuronal-specific markers. Increased cell
      proliferation is accompanied by activation of CREB phosphorylation in dentate
      gyrus granule cells, suggesting a role for this transcription factor. This
      possibility is supported by studies demonstrating that cell proliferation is
      decreased in conditional transgenic mice that express a dominant negative mutant
      of CREB in hippocampus. The results suggest that the cAMP-CREB cascade could
      contribute to the actions of neurotransmitters and neurotrophic factors on adult
      neurogenesis.

PMID- 11978844
TI  - Internally simulated movement sensations during motor imagery activate cortical
      motor areas and the cerebellum.
AB  - It has been proposed that motor imagery contains an element of sensory
      experiences (kinesthetic sensations), which is a substitute for the sensory
      feedback that would normally arise from the overt action. No evidence has been
      provided about whether kinesthetic sensation is centrally simulated during motor
      imagery. We psychophysically tested whether motor imagery of palmar flexion or
      dorsiflexion of the right wrist would influence the sensation of illusory palmar
      flexion elicited by tendon vibration. We also tested whether motor imagery of
      wrist movement shared the same neural substrates involving the illusory sensation
      elicited by the peripheral stimuli. Regional cerebral blood flow was measured
      with H215O and positron emission tomography in 10 right-handed subjects. The
      right tendon of the wrist extensor was vibrated at 83 Hz ("illusion") or at 12.5
      Hz with no illusion ("vibration"). Subjects imagined doing wrist movements of
      alternating palmar and dorsiflexion at the same speed with the experienced
      illusory movements ("imagery"). A "rest" condition with eyes closed was included.
      We identified common active fields between the contrasts of imagery versus rest
      and illusion versus vibration. Motor imagery of palmar flexion psychophysically
      enhanced the experienced illusory angles of plamar flexion, whereas dorsiflexion
      imagery reduced it in the absence of overt movement. Motor imagery and the
      illusory sensation commonly activated the contralateral cingulate motor areas,
      supplementary motor area, dorsal premotor cortex, and ipsilateral cerebellum. We
      conclude that kinesthetic sensation associated with imagined movement is
      internally simulated during motor imagery by recruiting multiple motor areas.

PMID- 11978845
TI  - The requirement of presynaptic metabotropic glutamate receptors for the
      maintenance of locomotion.
AB  - Spinal circuits known as central pattern generators maintain vertebrate
      locomotion. In the lamprey, the contralaterally alternating ventral root activity
      that defines this behavior is driven by ipsilateral glutamatergic excitation
      (Buchanan and Grillner, 1987) coupled with crossed glycinergic inhibition
      (Buchanan, 1982; Alford and Williams, 1989). These mechanisms are distributed
      throughout the spinal cord. Glutamatergic excitatory synapses activate AMPA and
      NMDA receptors known to be necessary for the maintenance of the locomotor rhythm.
      Less is known of the role and location of metabotropic glutamate receptors
      (mGluRs), although group I mGluRs enhance transmitter release at giant synapses
      in the lamprey spinal cord, whereas group II/III receptors may inhibit release.
      In this study we show that group I mGluR antagonists block fictive locomotion, a
      neural correlate of locomotion, by acting at the presynaptic terminal. Under
      physiological conditions, synaptically released glutamate activates presynaptic
      group I mGluRs (autoreceptors) during the repetitive activation of glutamatergic
      terminals. The resulting rise in [Ca2+]i caused by the release from presynaptic
      intracellular stores is coincident with an enhancement of synaptic transmission.
      Thus, blocking mGluRs reduces glutamate release during the repetitive activity
      that is characteristic of locomotion, leading to the arrest of locomotor
      activity. We found the effects of group I mGluRs on locomotion to be inconsistent
      with a postsynaptic effect on the central pattern generator. Consequently, the
      activation of metabotropic glutamate autoreceptors is necessary to maintain
      rhythmic motor output. Our results demonstrate the role of presynaptic mGluRs in
      the physiological control of movement for the first time.

PMID- 11978846
TI  - Cyclin-dependent kinase 5 is required for associative learning.
AB  - Transient stressful experiences may persistently facilitate associative and
      nonassociative learning, possibly through alterations of gene expression. Here we
      identify, by subtractive hybridization, differential expression of the Cdk5 gene
      in response to stress. The Cdk5 protein is selectively induced in the fibers of
      septohippocampal cholinergic neurons but not in other regions of prominent Cdk5
      production. This upregulation is accompanied by increased Cdk5 kinase activity,
      which is blocked completely by the Cdk5 inhibitor butyrolactone I. Microinjection
      of butyrolactone I into the lateral septum and hippocampus prevents the
      acquisition of conditioned context-dependent fear as well as its stress-induced
      facilitation. By demonstrating that a transient increase of Cdk5 activity within
      the septohippocampal system is required for associative learning, an important
      novel role of Cdk5 has been identified.

PMID- 11978847
TI  - Prefrontal dopamine D1 receptors and working memory in schizophrenia.
AB  - Studies in nonhuman primates documented that appropriate stimulation of dopamine
      (DA) D1 receptors in the dorsolateral prefrontal cortex (DLPFC) is critical for
      working memory processing. The defective ability of patients with schizophrenia
      at working memory tasks is a core feature of this illness. It has been postulated
      that this impairment relates to a deficiency in mesocortical DA function. In this
      study, D1 receptor availability was measured with positron emission tomography
      and the selective D1 receptor antagonist [11C]NNC 112 in 16 patients with
      schizophrenia (seven drug-naive and nine drug-free patients) and 16 matched
      healthy controls. [11C]NNC 112 binding potential (BP) was significantly elevated
      in the DLPFC of patients with schizophrenia (1.63 +/- 0.39 ml/gm) compared with
      control subjects (1.27 +/- 0.44 ml/gm; p = 0.02). In patients with schizophrenia,
      increased DLPFC [11C]NNC 112 BP was a strong predictor of poor performance at the
      n-back task, a test of working memory. These findings confirm that alteration of
      DLPFC D1 receptor transmission is involved in working memory deficits presented
      by patients with schizophrenia. Increased D1 receptor availability observed in
      patients with schizophrenia might represent a compensatory (but ineffective)
      upregulation secondary to sustained deficiency in mesocortical DA function.

PMID- 11978849
TI  - Congenic mapping of alcohol and pentobarbital withdrawal liability loci to a <1
      centimorgan interval of murine chromosome 4: identification of Mpdz as a
      candidate gene.
AB  - Risk for onset of alcoholism is related to genetic differences in acute alcohol
      withdrawal liability. We previously mapped a locus responsible for 26% of the
      genetic variance in acute alcohol withdrawal convulsion liability to a >35
      centimorgan (cM) interval of murine chromosome 4. Here, we narrow the position of
      this locus to a <1 cM interval (approximately 1.8 megabase, containing 15 genes
      and/or predicted genes) using a combination of novel, interval-specific congenic
      strains and recombinant progeny testing. We report the development of a small
      donor-segment congenic strain, which confirms capture of a gene affecting alcohol
      withdrawal within the <1 cM interval. We also confirm a pentobarbital withdrawal
      locus within this interval, suggesting that the same gene may influence
      predisposition to physiological dependence on alcohol and a barbiturate. This
      congenic strain will be invaluable for determining whether this interval also
      harbors a gene(s) underlying other quantitative trait loci mapped to chromosome
      4, including loci affecting voluntary alcohol consumption, alcohol-induced
      ataxia, physical dependence after chronic alcohol exposure, and seizure response
      to pentylenetetrazol or an audiogenic stimulus. To date, Mpdz, which encodes the
      multiple PSD95/DLG/ZO-1 (PDZ) domain protein (MPDZ), is the only gene within the
      interval shown to have allelic variants that differ in coding sequence and/or
      expression. Sequence analysis of 15 standard inbred mouse strains identifies six
      Mpdz haplotypes that predict three MPDZ protein variants. These analyses, and
      evidence using interval-specific congenic lines, show that alcohol withdrawal
      severity is genetically correlated with MPDZ status, indicating that MPDZ
      variants may influence alcohol withdrawal liability.

PMID- 11978850
TI  - Oscillatory neuronal synchronization in primary visual cortex as a correlate of
      stimulus selection.
AB  - Spike and local field potential activity were recorded simultaneously from
      multiple sites in primary visual cortex of strabismic cats, while monocular
      stimulation alternated with dichoptic stimulation, inducing interocular rivalry.
      During interocular rivalry, there is competition between the two nonfusible
      stimuli presented to the two eyes, and only one stimulus is selected at any time.
      We biased this competition in three different ways: (1) we exploited the
      condition that in strabismic cats there is often one dominant eye that is
      selected for most of the time. (2) We presented the two stimuli with a temporal
      offset, which biases competition in favor of the newly appearing stimulus. (3) We
      presented the two stimuli with highly different contrasts, which biases
      competition in favor of the stimulus with higher contrast. Whenever competition
      was biased in favor of the stimulus activating the recorded neurons, gamma
      frequency synchronization of the respective responses was enhanced, and vice
      versa. Firing rates showed some differences between stimulation conditions.
      However, when present, these changes were inversely related to a competitive
      advantage of the respective stimulus. We hypothesize that enhanced gamma
      frequency synchronization in primary visual cortex is a correlate of stimulus
      selection. Synchronization is likely to be translated into firing rate changes at
      later processing stages.

PMID- 11978848
TI  - Genetic contributions to altered callosal morphology in schizophrenia.
AB  - Patients with schizophrenia exhibit abnormalities in midsagittal corpus callosum
      area, shape, and/or displacement. Our goal was to confirm these findings and to
      establish the genetic and nongenetic contributions to altered callosal morphology
      in schizophrenia. Relationships between ventricular enlargements potentially
      contributing to callosal displacements were assessed as a secondary goal. High
      resolution magnetic resonance images were obtained from co-twins of monozygotic
      and dizygotic pairs discordant for schizophrenia and healthy control twins (N =
      40 pairs). Investigators blind to group status segmented the corpus callosum and
      ventricles in native brain volumes aligned using a rigid-body transformation with
      no scaling. Total and parcellated midsagittal callosal areas and measures
      indexing vertical displacements of the corpus callosum were used in statistical
      tests to identify schizophrenia and sex effects and to dissociate genetic and
      nongenetic influences on morphology. Anatomical mesh modeling methods provided
      group average and surface variability maps of the callosum. Callosal areas did
      not differ between groups defined by sex or biological risk. Vertical
      displacements of the callosum, pronounced in male patients, were confirmed in
      schizophrenia and observed between dizygotic, but not monozygotic co-twins
      discordant for schizophrenia. Like their affected twins, however, unaffected
      monozygotic co-twins of the schizophrenia probands exhibited significant callosal
      displacements. Lateral and third ventricle enlargements were related to callosal
      displacements. Results clearly support that genetic rather than disease-specific
      or shared environmental influences contribute to altered callosal morphology in
      schizophrenia. An upward bowing of the callosum may thus provide an easily
      identifiable neuroanatomic marker to screen individuals possessing a biological
      vulnerability for schizophrenia.

PMID- 11978851
TI  - Depressor and tachypneic responses to chemical stimulation of the ventral
      respiratory group are reduced by ablation of neurokinin-1 receptor-expressing
      neurons.
AB  - Our goal was to investigate whether the neurokinin-1 receptor (NK1R)-expressing
      cells of the rostral ventrolateral medulla (RVLM) regulate respiration and
      arterial pressure (AP). We examined the consequences of their ablation on the
      cardiorespiratory responses [phrenic nerve discharge (PND) and AP] caused by
      injecting dl-homocysteic acid (DLH) into the ventral respiratory group (VRG). In
      intact rats, DLH produced tachypnea only when injected into the pre-Botzinger
      complex (pre-BotC). Injections into pre-BotC and rostral VRG (rVRG) caused
      hypotension, whereas injections into the Botzinger region elevated AP. Selective
      unilateral ablation of RVLM NK1R-immunoreactive cells (97% loss within the pre
      BotC and rVRG without loss of catecholaminergic neurons) was done by injecting
      saporin (SAP) conjugated with a selective NK1R agonist [Sar9, Met(O2)11]
      substance P (SSP). Free SAP produced no lesion. Resting AP was normal in SAP- and
      SSP-SAP-treated rats, but the PND rate was slightly elevated in SSP-SAP-treated
      rats. The response of SAP-treated rats to DLH injection into VRG was normal and
      identical on each side, but tachypnea could not be elicited in the pre-BotC of
      SSP-SAP-treated rats on the toxin-injected side, and DLH caused a long-lasting
      apnea on the untreated side. The hypotension produced by DLH injection into pre
      BotC and rVRG of SSP-SAP-treated rats was reduced on the lesioned side only. In
      conclusion, NK1R-expressing cells of the rostral ventrolateral medulla control
      both respiratory rhythm and blood pressure. However, there is no evidence yet
      that these two functions are regulated by the same NK1R-expressing neurons.

PMID- 11978852
TI  - The GABA(A) receptor alpha1 subtype in the ventral pallidum regulates alcohol
      seeking behaviors.
AB  - We investigated the potential role of the alpha1-containing GABA(A) receptor in
      regulating the reinforcing properties of alcohol. To accomplish this, we
      developed 3-propoxy-beta-carboline hydrochloride (3-PBC), a mixed agonist
      antagonist benzodiazepine site ligand with binding selectivity at the alpha1
      receptor. We then tested the capacity of 3-PBC to block alcohol-maintained
      responding in the ventral pallidum (VP), a novel alcohol reward substrate, which
      primarily expresses the alpha1-receptor isoform. Our results demonstrated that
      bilateral microinfusion of 3-PBC (0.5-40 microg) in the anterior and medial VP
      produced marked reductions in alcohol-maintained responding in a genetically
      selected rodent model of alcohol drinking. The VP infusions showed both
      neuroanatomical and reinforcer specificity because no effects were seen in sites
      dorsal to the VP (e.g., nucleus accumbens, caudate putamen). The saccharin
      maintained responding was reduced only with the highest dose (40 microg).
      Parenteral injections of 3-PBC (1-20 mg/kg) also showed a similar selectivity on
      alcohol-maintained responding. Complementary in vitro studies revealed that 3-PBC
      exhibited a low partial agonist efficacy profile at recombinant diazepam
      sensitive receptors (e.g., alpha1beta3gamma2, alpha2beta3gamma, and
      alpha3beta3gamma2). The selective suppression of 3-PBC on alcohol-maintained
      responding after central and parenteral administrations, together with its low
      efficacy agonist profile, suggest that the reduction in alcohol-maintained
      behaviors was not attributable to a general suppression on consummatory
      behaviors. These results demonstrate that the alpha1-containing GABA(A) receptors
      in both the anterior and medial VP are important in regulating the reinforcing
      properties of alcohol. These receptors represent novel targets in the design and
      development of pharmacotherapies for alcohol-dependent subjects.

PMID- 11978853
TI  - A telencephalic nucleus essential for song learning contains neurons with
      physiological characteristics of both striatum and globus pallidus.
AB  - The song system of oscine birds has frequently been presented as a model system
      for motor learning in vertebrates. This practice has been bolstered by the
      growing recognition that one part of the song system that is essential for song
      learning, area X, is a component of the avian striatum. The mammalian striatum,
      the input structure of the basal ganglia, has been implicated in a number of
      motor-related functions, including motor learning, suggesting that song learning
      in birds and motor learning in mammals may use similar physiological mechanisms.
      We studied the intrinsic physiological properties of area X neurons in brain
      slices to see how closely they match properties identified in mammalian striatal
      neurons and to collect data that are necessary to understand how area X processes
      information. We found that area X contains all four physiological cell types
      present in the mammalian striatum and that each is very similar to its mammalian
      counterpart. We also found a fifth cell type in area X that has not been reported
      in mammalian striatum; instead, this cell type resembles neurons that have been
      recorded in the mammalian globus pallidus. This pallidum-like cell type
      morphologically resembles the projection neurons of area X. We suggest that area
      X contains a pathway equivalent to the "direct" striatopallidothalamic pathway
      through the mammalian basal ganglia, with the striatal and pallidal components
      intermingled in one nucleus.

PMID- 11978854
TI  - Priming of long-term potentiation in mouse hippocampus by corticotropin-releasing
      factor and acute stress: implications for hippocampus-dependent learning.
AB  - In the present experiments, we characterized the action of human/rat
      corticotropin-releasing factor (h/rCRF) and acute stress (1 hr of immobilization)
      on hippocampus-dependent learning and on synaptic plasticity in the mouse
      hippocampus. We first showed that h/rCRF application and acute stress facilitated
      (primed) long-term potentiation of population spikes (PS-LTP) in the mouse
      hippocampus and enhanced context-dependent fear conditioning. Both the priming of
      PS-LTP and the improvement of context-dependent fear conditioning were prevented
      by the CRF receptor antagonist [Glu(11,16)]astressin. PS-LTP priming and improved
      learning were also reduced by the protein kinase C inhibitor bisindolylmaleimide
      I. Acute stress induced the activation of Ca2+/calmodulin-dependent kinase II
      (CaMKII) 2 hr after the end of the stress session. The CaMKII inhibitor KN-62
      antagonized the stress-mediated learning enhancement, however, with no effect on
      PS-LTP persistence. Thus, long-lasting increased neuronal excitability as
      reflected in PS-LTP priming appeared to be essential for the enhancement of
      learning in view of the observation that inhibition of PS-LTP priming was
      associated with impaired learning. Conversely, it was demonstrated that
      inhibition of CaMKII activity reduced contextual fear conditioning without
      affecting PS-LTP priming. This observation suggests that priming of PS-LTP and
      activation of CaMKII represent two essential mechanisms that may contribute
      independently to long-term memory.

PMID- 11978855
TI  - Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A)
      receptor function and seizure susceptibility.
AB  - Stress affects seizure susceptibility in animals and humans, but the underlying
      mechanisms are obscure. Here, we provide evidence that GABA(A) receptor
      modulating neurosteroids derived from deoxycorticosterone (DOC) play a role in
      stress-related changes in seizure control. DOC, an adrenal steroid whose
      synthesis is enhanced during stress, undergoes sequential metabolic reduction by
      5alpha-reductase and 3alpha-hydroxysteroid oxidoreductase to form 5alpha
      dihydrodeoxycorticosterone (DHDOC) and allotetrahydrodeoxycorticosterone (THDOC),
      a GABA(A) receptor-modulating neurosteroid with anticonvulsant properties. Acute
      swim stress in rats significantly elevated plasma THDOC concentrations and raised
      the pentylenetetrazol (PTZ) seizure threshold. Small systemic doses of DOC
      produced comparable increases in THDOC and PTZ seizure threshold. Pretreatment
      with finasteride, a 5alpha-reductase inhibitor that blocks the conversion of DOC
      to DHDOC, reversed the antiseizure effects of stress. DOC also elevated plasma
      THDOC levels and protected mice against PTZ, methyl-6,7-dimethoxy-4-ethyl-beta
      carboline-3-carboxylate, picrotoxin, and amygdala-kindled seizures in mice (ED50
      values, 84-97 mg/kg). Finasteride reversed the antiseizure activity of DOC (ED50,
      7.2 mg/kg); partial antagonism was also obtained with indomethacin (100 mg/kg),
      an inhibitor of 3alpha-hydroxysteroid oxidoreductase. Finasteride had no effect
      on seizure protection by DHDOC and THDOC, whereas indomethacin partially reversed
      DHDOC but not THDOC. DHDOC, like THDOC, potentiated GABA-activated Cl- currents
      in cultured hippocampal neurons (< or =1 microm) and directly activated GABA(A)
      receptor currents (> or =1 microm), compatible with a role for DHDOC in the
      antiseizure activity of DOC. DOC is a mediator of the physiological effects of
      acute stress that could contribute to stress-induced changes in seizure
      susceptibility through its conversion to neurosteroids with modulatory actions on
      GABA(A) receptors including THDOC and possibly also DHDOC.

PMID- 11978856
TI  - Neurokinin-1 receptor-expressing cells of the ventral respiratory group are
      functionally heterogeneous and predominantly glutamatergic.
AB  - According to a recent theory (Gray et al., 1999) the neurokinin-1 receptor (NK1R)
      immunoreactive (ir) neurons of the ventral respiratory group (VRG) are confined
      to the pre-Botzinger complex (pre-BotC) and might be glutamatergic interneurons
      that drive respiratory rhythmogenesis. In this study we tested whether the NK1R
      ir neurons of the VRG are glutamatergic. We also examined whether different
      groups of NK1R-ir neurons coexist in the VRG on the basis of whether these cells
      contain preproenkephalin (PPE) mRNA or project to the spinal cord. NK1R
      immunoreactivity was found in two populations of VRG neurons that are both
      predominantly glutamatergic because most of them contained vesicular glutamate
      transporter 2 mRNA (77 +/- 9%; n = 3). A group of small fusiform neurons (somatic
      cross section: 91 +/- 3.6 microm2) that has neither PPE mRNA nor spinal
      projections is primarily restricted to the pre-BotC. These cells may be the
      interneurons the destruction of which produces massive disruptions of the
      respiratory rhythm (Gray et al., 2001). The rest of the NK1R-ir neurons of the
      VRG are multipolar, are larger (somatic cross section: 252 +/- 15 microm2), and
      express high levels of PPE mRNA. Some of these cells located in the rostral half
      of the rostral VRG project to the spinal cord (C4 or T3). Using
      electrophysiological methods, we showed that these bulbospinal NK1R-ir neurons
      are slowly discharging inspiratory-augmenting neurons, suggesting that they may
      control phrenic or intercostal motor neurons. In summary, NK1R-expressing cells
      of the VRG are a heterogeneous group of predominantly glutamatergic neurons that
      include subpopulations of respiratory premotor neurons.

PMID- 11978857
TI  - Contrasting patterns of receptive field plasticity in the hippocampus and the
      entorhinal cortex: an adaptive filtering approach.
AB  - Neural receptive fields are frequently plastic: a neural response to a stimulus
      can change over time as a result of experience. We developed an adaptive point
      process filtering algorithm that allowed us to estimate the dynamics of both the
      spatial receptive field (spatial intensity function) and the interspike interval
      structure (temporal intensity function) of neural spike trains on a millisecond
      time scale without binning over time or space. We applied this algorithm to both
      simulated data and recordings of putative excitatory neurons from the CA1 region
      of the hippocampus and the deep layers of the entorhinal cortex (EC) of awake,
      behaving rats. Our simulation results demonstrate that the algorithm accurately
      tracks simultaneous changes in the spatial and temporal structure of the spike
      train. When we applied the algorithm to experimental data, we found consistent
      patterns of plasticity in the spatial and temporal intensity functions of both
      CA1 and deep EC neurons. These patterns tended to be opposite in sign, in that
      the spatial intensity functions of CA1 neurons showed a consistent increase over
      time, whereas those of deep EC neurons tended to decrease, and the temporal
      intensity functions of CA1 neurons showed a consistent increase only in the
      "theta" (75-150 msec) region, whereas those of deep EC neurons decreased in the
      region between 20 and 75 msec. In addition, the minority of deep EC neurons whose
      spatial intensity functions increased in area over time fired in a significantly
      more spatially specific manner than non-increasing deep EC neurons. We
      hypothesize that this subset of deep EC neurons may receive more direct input
      from CA1 and may be part of a neural circuit that transmits information about the
      animal's location to the neocortex.

PMID- 11978858
TI  - The diversity of ganglion cells in a mammalian retina.
AB  - We report a survey of the population of ganglion cells in the rabbit retina. A
      random sample of 301 neurons in the ganglion cell layer was targeted for
      photofilling, a method in which the arbors of the chosen neurons are revealed by
      diffusion of a photochemically induced fluorescent product from their somas. An
      additional 129 cells were labeled by microinjection of Lucifer yellow. One
      hundred and thirty-eight cells were visualized by expression of the gene encoding
      a green fluorescent protein, introduced by particle-mediated gene transfer. One
      hundred and sixty-six cells were labeled by particle-mediated introduction of
      DiI. In the total population of 734 neurons, we could identify 11 types of
      retinal ganglion cell. An analysis based on retinal coverage shows that this
      number of ganglion cell types would not exceed the available total number of
      ganglion cells. Although some uncertainties remain, this sample appears to
      account for the majority of the ganglion cells present in the rabbit retina. Some
      known physiological types could easily be mapped onto structural types, but half
      of them could not; a large set of poorly known codings of the visual input is
      transmitted to the brain.

PMID- 11978859
TI  - Substrate for cross-talk inhibition between thalamic barreloids.
AB  - A double-labeling protocol was used to determine whether thalamocortical and
      reticular thalamic cells with overlapping receptive fields form open or closed
      loop connections in the vibrissal system of the rat. Results show that individual
      reticular cells exclusively project to the barreloid representing the principal
      whisker of their receptive field. Furthermore, solid retrograde labeling of relay
      cells reveals that a large number extend dendrites outside their home barreloid.
      This feature, together with previous demonstrations that reticular thalamic axons
      principally contact the dendrites of relay cells, provide a morphological
      substrate for cross-talk inhibition between thalamic barreloids.

PMID- 11978860
TI  - Apparent motion: event-related functional magnetic resonance imaging of
      perceptual switches and States.
AB  - When spatially segregated visual stimuli are presented in alternation, subjects
      may perceive a single stimulus moving between the two positions (apparent
      motion). By adjusting spatial and temporal parameters, an ambiguous condition can
      be created in which perception of back-and-forth motion alternates with the
      perception of two stationary blinking stimuli. We presented subjects with such
      ambiguous stimuli, asked them to signal periods of perceived motion and blinking,
      and measured brain activity with functional magnetic resonance imaging. Multiple
      regression analysis revealed that early visual areas responded with equal
      strength during both perceptual conditions, whereas hMT+(V5) (the human motion
      complex that includes the human homolog of MT and its satellites) was more active
      during the perception of apparent motion. These results indicate that neurons in
      hMT+ participate in the constructive process that creates a continuous motion
      percept from a discontinuous visual input.

PMID- 11978862
TI  - Direct interaction and determination of binding domains among peroxisomal import
      factors in Arabidopsis thaliana.
AB  - We analyzed the role of Arabidopsis orthologues of human Pex14p, Pex5p and Pex7p
      that are central components of peroxisomal protein import machinery. Immunoblot
      analysis showed that AtPex14p and AtPex5p were present in most organs in
      Arabidopsis, suggesting that these factors play a role in the main protein import
      pathways for plant peroxisomes. Two-hybrid analysis showed that AtPex14p
      interacted with AtPex5p, but not with AtPex7p. In addition, AtPex7p was bound to
      AtPex5p, indicating that the PTS2 pathway depends on the PTS1 pathway in
      Arabidopsis. Further analysis showed that the nine WXXXF/Y repeats in the amino
      acids 231K-450D and 1M-230V of AtPex5p are bound to two N-terminal domains, amino
      acids 58I-65L and 78R-97R of AtPex14p and the C-terminal amino acids 266Y-317S of
      AtPex7p, respectively. Since the binding domains of AtPex5p to AtPex14p and
      AtPex7p do not overlap, AtPex14p, AtPex5p and AtPex7p might form their complex
      and function cooperatively in peroxisomal protein import.

PMID- 11978861
TI  - Transforming growth factor beta1 alters synapsin distribution and modulates
      synaptic depression in Aplysia.
AB  - Transforming growth factor beta1 (TGF-beta1) induces long-term synaptic
      facilitation and long-term increases in excitability in Aplysia. Here we report
      that this growth factor has acute effects as well. Treatment of pleural-pedal
      ganglia with TGF-beta1 for 5 min activated mitogen-activated protein kinase
      (MAPK) and stimulated the phosphorylation of synapsin in a MAPK-dependent manner.
      This phosphorylation appeared to modulate synapsin distribution in cultured
      sensory neurons. Control neurons exhibited a punctate distribution of synapsin
      along neurites, which appeared to represent high concentration aggregates of
      synapsin. TGF-beta1-treated sensory neurons showed a significant reduction in the
      number of these puncta, an effect that was blocked by the MAP/ERK kinase
      inhibitor U0126. The functional consequence of TGF-beta1 was tested by examining
      its effects on synaptic transmission at the sensorimotor synapse. Application of
      TGF-beta1 reduced the magnitude of synaptic depression. This effect was dependent
      on MAPK, consistent with the hypothesis that TGF-1 mobilizes synaptic vesicles
      through the phosphorylation of synapsin.

PMID- 11978864
TI  - The leaf index: heteroblasty, natural variation, and the genetic control of polar
      processes of leaf expansion.
AB  - The morphology of the leaves of angiosperms exhibits remarkable diversity. One of
      the factors showing the greatest variability is the leaf index, namely, the ratio
      of leaf length to leaf width. In some cases, different varieties of a single
      species or closely related species can be distinguished by differences in leaf
      index. To some extent, the leaf index reflects the morphological adaptation of
      leaves to a particular environment. Moreover, physiological conditions or
      environmental factors can change the leaf index of an individual plant. No good
      tools have been available for studies of the mechanisms that underlie such
      biodiversity. However, we have recently obtained some, albeit fragmentary,
      information about molecular mechanisms of leaf morphogenesis as a result of
      studies of leaves of the model plant, Arabidopsis thaliana (L.) Heynh. For
      example, the ANGUSTIFOLIA gene, a homolog of animal CtBP genes, controls leaf
      width. ANGUSTIFOLIA appears to regulate the polar elongation of leaf cells via
      control of the arrangement of cortical microtubules. By contrast, the
      ROTUNDIFOLIA3 gene controls leaf length via the biosynthesis of steroid(s). We
      provide here an overview of the biodiversity exhibited by the leaf index of
      angiosperms. In particular, we consider information obtained from studies of
      mutants and transgenic strains of A. thaliana, from the so-called Evo/devo
      perspective.

PMID- 11978863
TI  - Blue light-induced chloroplast relocation.
AB  - Chloroplast relocation movement is induced by blue light in most plants tested.
      Under weak light, chloroplasts move toward a brighter area in a cell (called low
      fluence-rate response or accumulation movement), but they avoid strong light and
      move away from the light (called high-fluence-rate response or avoidance
      movement). Recently, mutants deficient in the chloroplast avoidance movement were
      isolated from Arabidopsis thaliana. The results of mutant analyses revealed that
      the phototropin photoreceptors phot1 and phot2 both control chloroplast
      accumulation while phot2 alone controls the avoidance movements.

PMID- 11978865
TI  - Effects of light and low oxygen tension on pigment biosynthesis in Halobacterium
      salinarum, revealed by a novel method to quantify both retinal and carotenoids.
AB  - A novel method for analyzing halobacterial pigments was developed, in which
      retinal was liberated from halobacterial rhodopsins as retinal oxime by
      hydroxylamine, ethyl beta-apo-8'-carotenoate was introduced as an internal
      standard, and the pigments including bacterioruberin and beta-carotene were
      analyzed by HPLC at the same time. With this method, we revealed that light
      enhances the biosynthesis of bacterioruberin and the conversion of beta-carotene
      to retinal, but does not affect beta-carotene biosynthesis in Halobacterium
      salinarum strain Oyon Moussa-16. Low oxygen tension given in the light brought a
      slight increase in retinal accumulation, although its biosynthesis from beta
      carotene is an oxygenation reaction. This paradox could be explained by the
      increase in beta-carotene biosynthesis.

PMID- 11978866
TI  - Visualization of peroxisomes in living plant cells reveals acto-myosin-dependent
      cytoplasmic streaming and peroxisome budding.
AB  - Here we examine peroxisomes in living plant cells using transgenic Arabidopsis
      thaliana plants expressing the green fluorescent protein (GFP) fused to the
      peroxisome targeting signal 1 (PTS1). Using time-lapse laser scanning confocal
      microscopy we find that plant peroxisomes exhibit fast directional movement with
      peak velocities approaching 10 microm s(-1). Unlike mammalian peroxisomes which
      move on microtubules, plant peroxisome movement is dependent on actin
      microfilaments and myosin motors, since it is blocked by treatment with
      latrunculin B and butanedione monoxime, respectively. In contrast, microtubule
      disrupting drugs have no effect on peroxisome streaming. Peroxisomes were further
      shown to associate with the actin cytoskeleton by the simultaneous visualization
      of actin filaments and peroxisomes in living cells using GFP-talin and GFP-PTS1
      fusion proteins, respectively. In addition, peroxisome budding was observed,
      suggesting a possible mechanism of plant peroxisome proliferation. The strong
      signal associated with the GFP-PTS1 marker also allowed us to survey cytoplasmic
      streaming in different cell types. Peroxisome movement is most intense in
      elongated cells and those involved in long distance transport, suggesting that
      higher plants use cytoplasmic streaming to help transport vesicles and organelles
      over long distances.

PMID- 11978867
TI  - Water uptake and hydraulic properties of elongating cells in hydrotropically
      bending roots of Pisum sativum L.
AB  - The water potential and hydraulic conductivity (Lp) of elongating cells in
      hydrotropically bending roots of the ageotropic mutant ageotropum of pea (Pisum
      sativum L.) were measured in situ. When agar blocks with water potentials of 
      0.03 and -0.8 MPa were unilaterally applied directly to a root tip, cells in the
      most rapidly elongating zone, 3-4 mm from the tip, showed marked differential
      growth. The rate of water uptake by a cell on the side treated with an agar block
      with a lower water potential was significantly larger in the outer first and
      second layers of cortex than on the other side. There were no differences in the
      values of turgor pressure, osmotic potential and calculated water potential
      between the two sides either in elongating or in mature cells, indicating the
      absence of any difference in the growth-induced water potential on the two sides
      of the root. Lp was significantly larger on the side with the agar block with
      lower water potential. The results suggest that the difference in the rate of
      water uptake during the differential cell growth that occurs during root
      hydrotropism might be induced mainly by a change in Lp.

PMID- 11978868
TI  - Regulation of gene expression by low levels of ultraviolet-B radiation in Pisum
      sativum: isolation of novel genes by suppression subtractive hybridisation.
AB  - Suppression subtractive hybridisation was used to isolate genes differentially
      regulated by low levels (UV-B(BE,300) 0.13 W m(-2)) of ultraviolet-B radiation
      (UV-B; 290-320 nm) in Pisum sativum. Six genes were regulated, two of which were
      novel. The mRNA levels for these two (PsTSDC and PsUOS1) were increased and
      depressed by UV-B treatment, respectively. Domains in the PsTSDC translation
      product was similar to TIR (Toll-Interleukin-1 receptor-similar) domains and a NB
      ARC domain (nucleotide-binding domain in APAF-1, R gene products and CED-4). The
      PsUOS1 translation product was similar to an open reading frame in Arabidopsis.
      Genes encoding embryo-abundant protein (PsEMB) and S-adenosyl-L-methionine
      synthase (PsSAMS) were induced by UV-B, whereas the transcript levels for genes
      encoding sucrose transport protein (PsSUT) or ribulose-5-phosphate 3-epimerase
      (PsR5P3E) were decreased. These regulation patterns are novel, and the PsEMB and
      PsR5P3E sequences are reported for the first time. The stress-specificity of
      regulation of these genes were tested by ozone fumigation (100 ppb O(3)).
      Qualitatively, the similarity of expression after both UV-B and ozone exposure
      suggests that, for these genes, similar stress-response pathways are in action.

PMID- 11978869
TI  - Changes in the sugar composition and molecular mass distribution of matrix
      polysaccharides during cotton fiber development.
AB  - Cotton (Gossypium herbaceum L.) fiber development consists of a fiber elongation
      stage (up to 20 d post-anthesis) and a subsequent cell wall thickening stage.
      Cell wall analysis revealed that the extractable matrix (pectic and
      hemicellulosic) polysaccharides accounted for 30-50% of total sugar content in
      the fiber elongation stage but less than 3% in the cell wall thickening stage. By
      contrast, cellulose increased dramatically after the fiber elongation ceased. The
      amounts of extractable xyloglucans and arabinose- and galactose-containing
      polymers per seed increased in the early fiber elongation stage and decreased
      thereafter. The amounts of extractable acidic polymers and non-cellulosic beta
      glucans (mainly composed of beta-1,3-glucans) increased in parallel with fiber
      elongation and then decreased. The molecular masses of extractable non-cellulosic
      beta-glucans, and arabinose- and galactose-containing polymers decreased during
      both fiber elongation and cell wall thickening stages. The molecular mass of
      extractable xyloglucans also decreased during the fiber elongation stage, but
      this decrease ceased during the cell wall thickening stage. Conversely, the
      molecular size of acidic polymers in the extractable pectic fraction increased
      during both stages. Thus, not only the amounts but also the molecular size of the
      extractable matrix polysaccharides showed substantial changes during cotton fiber
      development.

PMID- 11978870
TI  - ACR4, a putative receptor kinase gene of Arabidopsis thaliana, that is expressed
      in the outer cell layers of embryos and plants, is involved in proper
      embryogenesis.
AB  - The surfaces of higher plants are characterized by epidermis, which usually
      consists of a single layer of cells. The epidermis is derived from the outer cell
      layer of the embryo or protoderm, which arises as a result of periclinal cell
      division. After seed germination, most of the epidermal cells of the aerial parts
      of plants are derived from the outer cell layer of the shoot apical meristem (the
      L1 layer). Thus, knowledge of how the protoderm and/or L1 layer is established is
      fundamental to understanding the morphogenesis of higher plants. Here, we report
      the isolation of a gene encoding an Arabidopsis homologue (ACR4) of the maize
      putative receptor kinase CRINKLY4 (CR4), which is involved in epidermal
      differentiation. The domain organization of the predicted amino acid sequence of
      ACR4 is essentially identical to that of CR4. ACR4-GFP fusion protein localized
      to the cell surface when expressed in tobacco cell (BY-2) culture. ACR4
      transcripts were detected in all the organs of the Arabidopsis plant. In
      developing embryos and shoot apices, ACR4 transcripts accumulated in protoderm
      and epidermis at relatively higher levels than in the inner tissues. Over
      expression of antisense ACR4 in Arabidopsis plants resulted in malformation of
      embryos to varying degrees. These results suggest that ACR4 is, at a minimum,
      involved in the normal morphogenesis of embryos, most likely through properly
      differentiating protoderm cells.

PMID- 11978872
TI  - Regulation of energy balance in photosystems in response to changes in CO2
      concentrations and light intensities during growth in extremely-high-CO2-tolerant
      green microalgae.
AB  - Regulation of energy balance in photosystems in response to extremely-high-CO2
      (40%) and low-CO2 (0.04%) stress was studied in extremely-high-CO2-tolerant green
      microalgae, Chlorococcum littorale and Chlorella sp. UK001. To investigate the
      energy input process, we assessed an F714/F685-ratio in a 77K fluorescence
      emission spectrum induced by 440-nm excitation in intact cells, which represents
      a ratio of fluorescence intensities derived from light-harvesting chlorophyll
      complexes in PSI and PSII. The F714/F685-ratio increased in several days after
      transferring C. littorale cells from air to 40% CO2, from 3% to 40% CO2 and from
      3% to air. In all cases, the increase in the F714/F685-ratio was observed in high
      cell density culture, but no or a little increase was apparent in sparse cell
      density culture, when these cultures were illuminated at 250 micromol photon m-2
      s-1. Even in the sparse culture, however, a similar increase in the F714/F685
      ratio was observed when C. littorale cells were transferred from 3% to 40% CO2 at
      20 micromol photon m-2 s-1. The cell density did not affect the F714/F685-ratio
      when CO2 concentration was kept at 3%. The activity of PSI electron (e-)
      transport was much higher in 40% CO2-grown cells than in 3% CO2-grown cells
      irrespective of the cell density during the culture, whereas the difference in
      PSII activity between them was small. The PSI activity at high cell density was
      higher also in air-grown cells than that in 3% CO2-grown cells. In both dense and
      sparse culture, 40% CO2-grown cells and air-grown cells showed higher relative
      quantum yield of PSI in the presence of DCMU than 3% CO2-grown cells, suggesting
      an increase in cyclic electron flow around PSI. Likewise, the increase in the
      F714/F685-ratio in response to the transfer to 40% CO2 was observed also in
      another extremely-high-CO2-tolerant alga, Chlorella sp. UK001. The possible role
      of the increases in the F714/F685-ratio, PSI/PSII activity ratio and cyclic e-
      transport activity in extremely-high-CO2 acclimation is discussed in comparison
      with low-CO2 acclimation.

PMID- 11978871
TI  - Comparison of the structure of the extrinsic 33 kDa protein from different
      organisms.
AB  - The psbO gene encoding the extrinsic 33 kDa protein of oxygen-evolving
      photosystem II (PSII) complex was cloned and sequenced from a red alga, Cyanidium
      caldarium. The gene encodes a polypeptide of 333 residues, of which the first 76
      residues served as transit peptides for transfer across the chloroplast envelope
      and thylakoid membrane. The mature protein consists of 257 amino acids with a
      calculated molecular mass of 28,290 Da. The sequence homology of the mature 33
      kDa protein was 42.9-50.8% between the red alga and cyanobacteria, and 44.7-48.6%
      between the red alga and higher plants. The cloned gene was expressed in
      Escherichia coli, and the recombinant protein was purified, subjected to protease
      treatments. The cleavage sites of the 33 kDa protein by chymotrypsin or V8
      protease were determined and compared among a cyanobacterium (Synechococcus
      elongatus), a euglena (Euglena gracilis), a green alga (Chlamydomonas
      reinhardtii) and two higher plants (Spinacia oleracea and Oryza sativa). The
      cleavage sites by chymotrypsin were at 156F and 190F for the cyanobacterium,
      159M, 160F and 192L for red alga, 11Y and 151F for euglena, 10Yand 150F for green
      alga, and 16Y for spinach, respectively. The cleavage sites by V8 protease were
      at 181E (cyanobacterium), 182E and 195E (red alga), 13E, 67E, 69E, 153D and 181E
      (euglena), 176E and 180E (green alga), and 18E or 19E (higher plants). Since most
      of the residues at these cleavage sites were conserved among the six organisms,
      the results indicate that the structure of the 33 kDa protein, at least the
      structure based on the accessibility by proteases, is different among these
      organisms. In terms of the cleavage sites, the structure of the 33 kDa protein
      can be divided into three major groups: cyanobacterial and red algal-type has
      cleavage sites at residues around 156-195, higher plant-type at residues 16-19,
      and euglena and green algal-type at residues of both cyanobacterial and higher
      plant-types.

PMID- 11978873
TI  - Cell wall invertase in developing rice caryopsis: molecular cloning of OsCIN1 and
      analysis of its expression in relation to its role in grain filling.
AB  - To establish the significance of cell wall invertase in grain filling of rice
      (Oryza sativa L.), we cloned a cDNA for a cell wall invertase from developing
      grains of rice. The cDNA, designated OsCIN1, contains an open reading frame of
      1731 bp encoding a polypeptide of 577 amino acid residues. The deduced amino acid
      sequence showed typical features of the cell wall invertases, including a beta
      fructosidase motif and a cysteine catalytic site, and shared 78.6 and 73.7%
      identity with maize cell wall invertases, Incw1 and Incw2, respectively. OsCIN1
      is expressed in roots, in sink- and source-leaves, and in panicles. During the
      course of grain filling in the caryopses, OsCIN1 transcript is detectable only in
      the very early stage of their development, 1-4 d after flowering, when the cell
      wall invertase activity is the highest and the increase in caryopsis length is
      rapid. In situ localization of the mRNA revealed that OsCIN1 is expressed
      preferentially in the vascular parenchyma of the dorsal vein, integument and its
      surrounding cells, and is expressed weakly in the nucellar projection and
      nucellar epidermis. These results suggest that, during the early stage of
      caryopsis development, OsCIN1 is important for supplying a carbon source to
      developing filial tissues by cleaving unloaded sucrose in the apoplast.

PMID- 11978874
TI  - A cAMP receptor protein, SYCRP1, is responsible for the cell motility of
      Synechocystis sp. PCC 6803.
AB  - Disruption of the sycrp1 gene encoding a cyanobacterial cAMP receptor protein
      makes cells of Synechocystis sp. PCC 6803 non-motile. Electron microscopy showed
      that the sycrp1-deficient strain had a reduced number of thick pili on the cell
      surface compared with the wild-type strain. It is suggested that cAMP-SYCRP1
      complex controls the biogenesis of pili.

PMID- 11978875
TI  - The risk of hematopoietic growth factor therapy in newborn infants.

PMID- 11978876
TI  - Insight into podocyte differentiation from the study of human genetic disease:
      nail-patella syndrome and transcriptional regulation in podocytes.
AB  - In recent years, our understanding of the molecular basis of kidney development
      has benefited from the study of rare genetic diseases affecting renal function.
      This has especially been the case with the differentiation of the highly
      specialized podocyte in the pathogenesis of human disorders and mouse phenotypes
      affecting the renal filtration barrier. This filtration barrier represents the
      end product of a complex series of signaling events that produce a tripartite
      structure consisting of interdigitating podocyte foot processes with intervening
      slit diaphragms, the glomerular basement membrane, and the fenestrated
      endothelial cell. Dysregulation of unique cytoskeletal and extracellular matrix
      proteins in genetic forms of nephrotic syndrome has shown how specific structural
      proteins contribute to podocyte function and differentiation. However, much less
      is known about the transcriptional determinants that both specify and maintain
      this differentiated cell. Our studies of a skeletal malformation syndrome, nail
      patella syndrome, have shown how the LIM homeodomain transcription factor, Lmx1b,
      contributes to transcriptional regulation of glomerular basement membrane
      collagen expression by podocytes. Moreover, they raise intriguing questions about
      more global transcriptional regulation of podocyte morphogenesis.

PMID- 11978877
TI  - Role of OmpA and IbeB in Escherichia coli K1 invasion of brain microvascular
      endothelial cells in vitro and in vivo.
AB  - Escherichia coli K1 is the most common Gram-negative organism causing neonatal
      meningitis, but it is incompletely understood how E. coli K1 crosses the blood
      brain barrier. We have previously identified several E. coli determinants
      contributing to invasion of brain microvascular endothelial cells (BMEC) in
      vitro, which include OmpA and IbeB. In the present study, we constructed a mutant
      (E98) by deleting only OmpA (isogenic OmpA deletion mutant) from E. coli K1
      strain RS218 (018:K1:H7) and also an isogenic OmpA deletion mutant from the ibeB
      deleted mutant (IB7D5) of strain RS218. As expected, the ompA and ibeB deletion
      mutants, E98 and IB7D5, respectively, were less invasive in BMEC in vitro
      compared with the parent strain. More importantly, their abilities to penetrate
      the blood-brain barrier were significantly less than those of the parent strain
      in the experimental hematogenous E. coli meningitis model. The combined ompA- and
      ibeB-deleted mutant, however, behaved similarly compared with its single-gene
      deletion mutants (E98 and IB7D5) in its ability to invade BMEC in vitro and to
      penetrate into the CNS in vivo. These findings indicate that OmpA and IbeB are
      the important determinants contributing to E. coli K1 crossing of the blood-brain
      barrier, but their contributions are not additive. Additional studies are needed
      to understand the reasons for no additive effect with OmpA and IbeB in E. coli K1
      penetration into the CNS.

PMID- 11978878
TI  - Quantitative near infrared spectroscopy measurement of cerebral hemodynamics in
      newborn piglets.
AB  - Severely premature infants are often at increased risk of cerebral hemorrhage
      and/or ischemic injury caused by immature autoregulatory control of blood flow to
      the brain. If blood flow is too high, the infant is at risk of hemorrhage,
      whereas too little blood flow can result in ischemic injury. The development of a
      noninvasive, bedside means of measuring cerebral hemodynamics would greatly
      facilitate both diagnosis and monitoring of afflicted individuals. It is to this
      end that we have developed a near infrared spectroscopy (NIRS) system that allows
      for quantitative, bedside measurement of cerebral blood flow (CBF), cerebral
      blood volume (CBV), and mean transit time (MTT). The technique requires an i.v.
      injection of the near infrared chromophore indocyanine green. Six newborn
      piglets, median age of 18 h (range 6-54 h), median weight of 1.75 kg (range 1.5
      2.1 kg), were studied. Measurements of CBF, CBV, and MTT were made at
      normocapnia, hypocapnia, and hypercapnia to test the technique over a range of
      hemodynamic conditions. The accuracy of our new approach has been determined by
      direct comparison with measurements made using a previously validated computed
      tomography technique. Paired t tests showed no significant difference between
      computed tomography and NIRS measurements of CBF, CBV, and MTT, and mean biases
      between the two methods were -2.05 mL x min(-1) x 100 g(-1), -0.18 mL x 100 g(
      1), and 0.43 s, respectively. The precision of NIRS CBF, CBV, and MTT
      measurements, as determined by repeated-measures ANOVA, was 9.71%, 13.05%, and
      7.57%, respectively.

PMID- 11978879
TI  - Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid
      after severe traumatic brain injury in infants and children.
AB  - Studies in experimental traumatic brain injury (TBI) support a key role for
      oxidative stress. The degree of oxidative injury in clinical TBI, however,
      remains to be defined. We assessed antioxidant defenses and oxidative stress in
      pediatric TBI by applying a comprehensive battery of assays to cerebrospinal
      fluid samples. Using a protocol approved by our institutional review board, 87
      cerebrospinal fluid samples from 11 infants and children with severe TBI (Glasgow
      Coma Scale score < or = 8) and 8 controls were studied. Cerebrospinal fluid was
      drained as standard care after TBI. CSF was assessed on d 1, 2, and 5-7 after
      ventricular drain placement. Biochemical markers of oxidative stress included
      F(2)-isoprostane and protein sulfhydryl (detected by ELISA and fluorescence
      assay, respectively). Antioxidant defenses were measured by determination of
      total antioxidant reserve (via chemiluminescence assay), and ascorbate (via HPLC)
      and glutathione (via fluorescence assay) concentrations. Free radical production
      (ascorbate radical) was assessed by electron paramagnetic resonance spectroscopy.
      F(2)-isoprostane was markedly increased versus control, maximal on d 1 (93.8 +/-
      30.8 pg/mL versus 7.6 +/- 5.1 pg/mL, p < 0.05). Total antioxidant reserve was
      reduced versus control. Reduction was maximal on d 5-7 (81.8 +/- 3.7 microM
      versus 178.9 +/- 2.2 microM, p < 0.05). Ascorbate was remarkably reduced (53.8 +/
      8 microM versus 163.8 +/- 21 microM on d 1, p < 0.05). Ascorbate depletion was
      likely associated with its free radical oxidation, as evidenced by electron
      paramagnetic resonance spectroscopy. Glutathione levels increased on d 1, then
      decreased versus control (0.19 +/- 0.05 microM versus 1.2 +/- 0.16 microM, p <
      0.05). This is the first comprehensive study of antioxidant reserve and oxidative
      injury in clinical TBI. Progressive compromise of antioxidant defenses and
      evidence of free radical-mediated lipid peroxidation are noted. These markers
      could be used to monitor antioxidant strategies in clinical trials.

PMID- 11978880
TI  - Cerebrovasodilatory contribution of endogenous carbon monoxide during seizures in
      newborn pigs.
AB  - Carbon monoxide (CO) and the excitatory amino acid glutamate both dilate cerebral
      arterioles in newborn pigs. The key enzyme in CO synthesis is heme oxygenase,
      which is highly expressed in neurons with glutamatergic receptor activity as well
      as cerebral microvessels. During seizures the extracellular level of glutamate is
      increased, which results in excessive depolarization of neurons. We hypothesized
      that CO is a mediator of excitatory amino acid-induced dilation of the cerebral
      microvasculature during seizures. Three groups of piglets were examined: 1) i.v.
      normal saline (sham control), 2) topical chromium mesoporphyrin (Cr-MP, 15 x 10(
      6) M), and 3) i.v. tin-protoporphyrin (Sn-PP, 4 mg/kg). Synthetic
      metalloporphyrins (Cr-MP and Sn-PP) are heme oxygenase inhibitors, thereby
      reducing CO synthesis. Implanted closed cranial windows were used to monitor
      changes in pial arteriolar diameters. Seizures were induced by administration of
      i.v. bicuculline. Changes in pial arteriolar diameters were monitored during 30
      min of status epilepticus. The percent increase in pial arteriolar dilation in
      the saline group during seizures was 68 +/- 3%. In the metalloporphyrin groups,
      the pial arteriolar dilation was markedly reduced (35 +/- 3% and 13 +/- 1%, for
      Cr-MP and Sn-PP, respectively; p < 0.05, compared with the saline group). We
      conclude that metalloporphyrins by inhibition of heme oxygenase and prevention of
      CO synthesis attenuate pial arteriolar dilation during seizures. Therefore, CO
      appears to be involved in cerebral vasodilation caused by glutamatergic seizures.

PMID- 11978881
TI  - NOC/oFQ and NMDA contribute to piglet hypoxic ischemic hypotensive
      cerebrovasodilation impairment.
AB  - Previous studies have observed that hypotensive pial artery dilation was blunted
      after hypoxia-ischemia. In unrelated studies, the opioid nociceptin/orphanin FQ
      (NOC/oFQ) was observed to contribute to hypoxic ischemic impairment of N-methyl-D
      aspartate (NMDA)-induced pial dilation. This study determined the contribution of
      NOC/oFQ and NMDA to hypoxic ischemic hypotensive cerebrovasodilation impairment
      in newborn pigs equipped with a closed cranial window. Global cerebral ischemia
      was produced via elevated intracranial pressure. Hypoxia decreased PO(2) to 33 +/
      3 mm Hg. Topical NOC/oFQ (10(-10) M), the cerebrospinal fluid concentration
      after hypoxia-ischemia, had no effect on pial artery diameter by itself but
      attenuated hypotension (mean arterial blood pressure decrease of 44 +/- 2%) 
      induced pial artery dilation (35 +/- 2% versus 22 +/- 3%). Hypotensive pial
      artery dilation was blunted by hypoxia-ischemia, but such dilation was partially
      protected by pretreatment with the putative NOC/oFQ receptor antagonist, [F/G]
      NOC/oFQ (1-13) NH(2) (10(-6) M; 29 +/- 2%, sham control; 7 +/- 2%, hypoxia
      ischemia; and 13 +/- 2%, hypoxia-ischemia and [F/G] NOC/oFQ (1-13) NH(2)).
      Coadministration of the NMDA antagonist MK801 (10(-5) M) with NOC/oFQ(10(-10) M)
      partially prevented hypotensive pial dilation impairment. Similarly, pretreatment
      with MK801 partially protected hypoxic ischemia impairment of hypotensive pial
      dilation (35 +/- 2%, sham control; 7 +/- 1%, hypoxia-ischemia; 22 +/- 2%, hypoxia
      ischemia + MK801). These data show that NOC/oFQ and NMDA contribute to hypoxic
      ischemic hypotensive cerebrovasodilation impairment. These data suggest that
      NOC/oFQ modulation of NMDA vascular activity also contributes to such hypotensive
      impairment.

PMID- 11978882
TI  - Lactate disposal via gluconeogenesis is increased during exercise in patients
      with mitochondrial myopathy due to complex I deficiency.
AB  - This study evaluated lactate disposal via gluconeogenesis as well as effects of
      FFA availability on gluconeogenesis via pyruvate (GNG(PYR)) in patients with
      mitochondrial myopathy due to complex I deficiency (CID). The rates of GNG(PYR)
      were measured in three CID patients and six healthy controls at rest and during
      90 min cycle exercise, using the deuterium-labeled water method. All subjects
      served as their own control: on one occasion they were studied in the fasting
      state, and on the second occasion they received an infusion of triacylglycerol
      plus heparin. At rest, the fractional rate of gluconeogenesis from pyruvate was
      higher in patients than in controls in the fasting state. Triacylglycerol
      infusion was associated with increased rates of GNG(PYR) at rest in controls (p <
      0.05) but not in patients. Circulating lactate and pyruvate levels were increased
      3-fold during exercise in the CID patients. During exercise, GNG(PYR) increased
      in the CID patients (p < 0.01) and remained unchanged in controls, resulting in
      85% and 72% higher absolute rates of GNG(PYR) in the patients than in the
      controls during fasting and triacylglycerol infusion, respectively. During
      exercise, rates of GNG(PYR) were not different between fasting and
      triacylglycerol infusion within both groups. Our data show that 1) GNG(PYR) is
      increased during exercise in CID patients; 2) increased pyruvate availability
      contributes to the higher rates of GNG(PYR) in the CID patients; and 3) exogenous
      infusion of fatty acids is not associated with increased rates of GNG(PYR) in CID
      patients at rest or during exercise. GNG(PYR) is a significant mechanism of
      lactate disposal in exercising CID patients, but triglyceride infusion does not
      enhance their lactate disposal through this mechanism.

PMID- 11978883
TI  - An unexpectedly high frequency of hypergalactosemia in an immigrant Bosnian
      population revealed by newborn screening.
AB  - In galactokinase (GALK) deficiency, galactose cannot be phosphorylated into
      galactose-1-phosphate, which leads to cataract formation. Neonatal screening for
      hypergalactosemia in Berlin has been performed by thin-layer chromatography since
      1978, which detects classical galactosemia and GALK deficiency. Until 1991, GALK
      deficiency has not been identified in a total of approximately 260,000 samples.
      In contrast, from 1992 to 1999, nine patients were detected in a total of
      approximately 240,000 screened newborns. One Turkish patient was homozygous for
      two novel S142I/G148C GALK mutations in close proximity to the putative ATP
      binding site of the enzyme. The other eight children were born to five families
      belonging to the Bosnian refugee population consisting of approximately 30,000
      individuals who have arrived in Berlin since 1991. In two of these families, GALK
      deficiency was subsequently diagnosed in siblings who had cataract surgery at 4
      and 5 y of age, respectively. In all these 10 Bosnian patients, a homozygous P28T
      mutation located near the active center of the enzyme was identified. We propose
      that neonatal screening of populations with a significant proportion of Bosnians
      and possibly other southeastern Europeans, e.g. Romani, should be particularly
      directed toward GALK deficiency, an inborn error of metabolism that is readily
      amenable to effective treatment.

PMID- 11978884
TI  - The P28T mutation in the GALK1 gene accounts for galactokinase deficiency in Roma
      (Gypsy) patients across Europe.
AB  - Galactokinase deficiency is an inborn error of metabolism that, if untreated,
      results in the development of cataracts in the first weeks of life. The disorder
      is rare worldwide, but has a high incidence among the Roma (Gypsies). In 1999, we
      reported the founder Romani mutation, P28T, identified in affected families from
      Bulgaria. Subsequent studies have detected the same mutation in Romani patients
      from different European countries. The screening of 803 unrelated control
      individuals of Romani ethnicity from Bulgaria, Hungary, and Spain has shown an
      overall carrier rate of 1:47 and an expected incidence of affected births about
      1:10,000. Using disease haplotype analysis, the age of the P28T mutation was
      estimated at 750 y, preceding the splits of the proto-Roma into the numerous
      populations resident in Europe today. The findings suggest that the mutation has
      spread with the early diaspora of the Roma throughout Europe. Superimposed on
      this old distribution pattern is the new migration wave of the last decade, with
      large numbers of Roma moving to Western Europe as a result of the economic
      changes in the East and the wars in former Yugoslavia. The changing demographic
      pattern of Romani minorities can be expected to lead to a homogenization of the
      incidence of "private" Romani disorders and founder mutations. The P28T mutation
      is thus likely to account for a high proportion of galactokinase deficiency cases
      across Europe. Mutation-based pilot newborn screening programs would provide
      current incidence figures and help to design long-term prevention of infantile
      cataracts due to galactokinase deficiency.

PMID- 11978885
TI  - CHS 828 inhibits neuroblastoma growth in mice alone and in combination with
      antiangiogenic drugs.
AB  - CHS 828 is a new chemotherapeutic drug, a pyridyl cyanoguanidine. CHS 828 has low
      toxicity and lacks known patterns of multidrug resistance. Here we report that
      oral, daily treatment with CHS 828 reduced the growth of SH-SY5Y human
      neuroblastoma tumors in male NMRI nu/nu mice by 82% without apparent toxicity.
      CHS 828 induced complete tumor regression for at least 5 weeks in four of nine
      animals (44%). Combination therapy with CHS 828 and the antiangiogenic drugs TNP
      470 or SU5416 decreased neuroblastoma growth by a further 10 and 3%,
      respectively. Combination therapy induced tumor regression at d 4 with CHS plus
      TNP and d 6 with CHS plus SU5416, compared with d 14 with CHS 828 alone (p <
      0.05), and complete tumor regression was seen in nine of 19 animals (47%).
      Combination treatment of CHS 828 and TNP-470 decreased the total viable tumor
      volume by 71% compared with treatment with CHS 828 alone. Our findings support
      CHS 828 as a promising new drug in treatment of childhood cancers. Furthermore,
      they imply efficiency of daily administration of nontoxic doses of chemotherapy,
      and a possible additive effect when chemotherapy is combined with angiogenesis
      inhibitors.

PMID- 11978886
TI  - Milk from mothers of both premature and full-term infants provides better
      antioxidant protection than does infant formula.
AB  - We hypothesized that premature (PT) infants' mother's milk may provide
      antioxidant advantages compared with milk from mothers of full-term (FT) infants,
      and human milk may provide antioxidant properties not seen in infant formulas. We
      designed three experiments to test these hypotheses. Experiment 1 assessed
      resistance to oxidative stress of human milk and formulas designed for FT and PT
      infants. Experiment 2 determined differences in resistance to oxidative stress
      between milk from mothers of FT and PT infants, including analysis of catalase
      activity. Experiment 3 examined factors in human milk that may account for
      increased resistance to oxidative stress. In experiment 1, we induced physiologic
      oxidative stress in human milk (n = 5) and formula (n = 2) and measured ascorbate
      radical using electron paramagnetic resonance. Results indicated the following:
      1) during oxidative stress, ascorbate may be spared in human milk compared with
      formula; 2) ascorbate radical production is more intense in formula compared with
      human milk, with or without oxidative stress; and 3) oxygen consumption in human
      milk is less than that in formula, with or without oxidative stress. In
      experiment 2, milk samples were collected from mothers of PT (n = 28) and FT (n =
      17) infants at wk 1, 2, and 12 of lactation. No differences in oxygen consumption
      after oxidative stress appeared between PT and FT milk. Catalase levels in human
      milk increased with time. In experiment 3, addition of catalase, superoxide
      dismutase, and glutathione peroxidase to formulas (n = 4) increased resistance to
      oxidative stress. Denaturing endogenous enzymes did not decrease the ability of
      human milk to resist oxidative stress. Ferrous sulfate plus vitamin C added to
      human milk and formulas fortified with iron increased oxidative stress. Addition
      of iron chelators to formula reduced oxidative stress. In conclusion, human milk
      has better antioxidant protection than do formulas, perhaps because of the higher
      iron content of formulas. Milk from mothers of PT and FT infants has equal
      resistance to oxidative stress.

PMID- 11978887
TI  - Presence of macrophage migration inhibitory factor in human milk: evidence in the
      aqueous phase and milk fat globules.
AB  - Human milk is a source of bioactive substances regulating the development and
      activity of the newborn immune system. Human milk has been found to contain a
      number of cytokines, including interleukins, growth factors, and colony
      stimulating factors. In the present study, we assessed 10 specimens of human milk
      for the presence of macrophage migration inhibitory factor (MIF), a cytokine
      recently described in several human reproductive organs and tissues. Using
      biochemical as well as immunologic techniques, we showed that MIF is abundantly
      present in human milk, mostly distributed in the lipid layer and in the aqueous
      phase. Fractionation of the lipid layer showed that MIF is highly concentrated
      inside milk fat globules. In view of its proinflammatory features, we speculate
      that milk MIF may protect the newborn against infection and play a role in
      preserving the functionality of the lactating mammary gland. Furthermore, the
      localization of MIF in lipid globules suggests a possible strategy for the
      protection of milk cytokines from the gastric barrier.

PMID- 11978888
TI  - Polyamine participation in the maturation of glycoprotein fucosylation, but not
      sialylation, in rat small intestine.
AB  - The aim of this study was to determine the role of polyamines in the diet-related
      maturation of the intestinal glycoprotein glycosylation during postnatal
      development in the rat. The activity of alpha-2,6-sialyltransferase and the
      sialylated forms of glycoproteins in the intestinal brush-border membranes were
      found to decrease considerably after weaning, in parallel with the intestinal
      level of putrescine. By contrast, the activity of alpha-1,2-fucosyltransferases,
      the mRNA levels for two alpha-1,2-fucosyltransferase genes, FTA and FTB, and the
      fucosylated forms of glycoproteins all increased after weaning, in parallel with
      the levels of spermidine and spermine. These results suggest a possible role of
      polyamines in the evolution of glycosylation. The treatment of suckling rats with
      spermidine or spermine reproduced the high intestinal levels of these polyamines
      corresponding to those normally found after weaning. After these treatments, a
      rise in the activity of the alpha-1,2-fucosyltransferase was observed, associated
      with a fall in alpha-L-fucosidase activity. The alpha-1,2-fucosyltransferase FTB
      gene was found to be regulated at the transcriptional level, but not by its
      inhibitor, fuctinin. The result of these variations was the precocious appearance
      of several alpha-1,2-fucoproteins, which are normally found in brush-border
      membranes after weaning. The treatment of suckling rats with putrescine, which
      induced only a transitory rise in intestinal putrescine, had a similar but weaker
      effect on the fucosylation process than spermidine or spermine, and treatment
      with ornithine was ineffective. alpha-2,6-Sialylation was not affected by any of
      the treatments. Spermidine and spermine turned out to be more effective than
      putrescine for intestinal glycoprotein fucosylation, but did not affect their
      sialylation. Spermidine and spermine, whose intestinal levels where found to
      increase at weaning time, may have been partly responsible for the natural
      evolution of the intestinal glycoprotein fucosylation that occurred during this
      period.

PMID- 11978889
TI  - Effect of heparin on tissue binding activity of fibroblast growth factor and
      heparin-binding epidermal growth factor in experimental colitis in rats.
AB  - There have been several reports implying a benefit for heparin therapy in
      patients with refractory ulcerative colitis. Although this effect has been
      attributed to the anti-inflammatory properties of heparin, other mechanisms have
      not been excluded. Heparin is a potent modulator of receptor binding of growth
      factors such as fibroblast growth factor (FGF), vascular endothelial growth
      factor, and heparin-binding epidermal growth factor (HB-EGF), that play a role in
      wound repair. We examined the effect of heparin on the functional levels of FGF
      and HB-EGF in a model of experimental colitis. Fifty-six Wistar rats were divided
      into four groups: group 1 was the control group, group 2 received s.c. heparin 50
      units/kg/d, group 3 underwent induction of 3% iodoacetamide colitis, and group 4
      underwent induction of colitis and heparin treatment. Rats were killed and
      evaluated for severity of colitis by macroscopic and microscopic colitis scores,
      area of inflammation, and myeloperoxidase levels. FGF and HB-EGF levels were
      functionally assessed in colonic tissue in each group. Heparin therapy resulted
      in significant improvement in macroscopic and microscopic features of colitis (p
      < 0.05), accompanied by a partial reduction in myeloperoxidase levels. FGF
      receptor binding activity was identical in groups 1 and 2 but increased more than
      3-fold after colitis induction in group 3 (p < 0.05). Treatment with heparin
      caused a significant decrease in FGF concentration. Levels of HB-EGF binding
      activity were similar in groups 1 and 2 and decreased in group 3 (p < 0.01).
      Heparin caused a significant increase in HB-EGF content in group 4 (p < 0.05).
      Levels of growth factors are altered differently in experimental colitis. Colonic
      FGF binding activity increases with colitis, whereas HB-EGF binding decreases
      with colitis. These trends were reversed by heparin, concomitant with a clinical
      and pathologic improvement in colitis. We suggest that one mechanism of heparin
      mediated improvement in colitis may involve tissue healing associated with
      changes in functional levels of colonic growth factors.

PMID- 11978890
TI  - Increased expression of extracellular glutathione peroxidase in mice with dextran
      sodium sulfate-induced experimental colitis.
AB  - Extracellular glutathione peroxidase (E-GPx) is a selenoenzyme that reduces
      hydrogen peroxide and organic peroxides. All plasma glutathione peroxidase (GPx)
      activity in humans is attributable to E-GPx. The gastrointestinal (GI) tract also
      synthesizes and secretes E-GPx into the extracellular milieu. Endogenously
      generated oxidants have been implicated in inflammatory bowel disease (IBD). We
      evaluated E-GPx levels in a mouse model of IBD using dextran sodium sulfate
      (DSS). Histologic lesions of the lower GI tract consisted of multifocal areas of
      mucosal erosion denuded of epithelial cells, reduction in goblet cells, dilated
      crypts, crypt collapse, submucosal edema, and transmural distribution of mixed
      inflammatory infiltrates. On d 7, plasma GPx activity in the DSS group increased
      by 61% compared with the control group (p < 0.05). Western blot analysis
      demonstrated a 64% increase in E-GPx protein in the plasma of the DSS group after
      7 d of treatment (p < 0.01). As the major source of plasma GPx is the kidney, we
      determined whether the increase in plasma GPx activity and protein was caused by
      a change in E-GPx synthesis by the kidney. After 3 and 7 d of DSS treatment, E
      GPx mRNA levels, relative to glyceraldehyde-3-phosphate dehydrogenase, increased
      in the kidney (p < 0.05) without a concomitant increase in cellular GPx mRNA on d
      7. These results suggest that the inflammatory injury in the intestine elicits an
      increase in E-GPx in the plasma that is associated with an increase in E-GPx mRNA
      in the kidney. This implies that renal production of E-GPx may be sensitive to
      insults distal to the kidney.

PMID- 11978891
TI  - Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of
      diabetic rats.
AB  - Maternal diabetes causes a range of complications in offspring, including reduced
      skeletal ossification. This study examined whether feeding gamma-linoleic acid
      (GLA) and ascorbate, alone or in combination, to diabetic pregnant rats improves
      skeletal development in their offspring. In addition, Ca(2+) concentration was
      monitored in maternal plasma and fetal tissue, as well as placental mRNA
      expression of calbindin-D(9k). Female rats rendered diabetic with streptozotocin
      were fed GLA (500 mg/kg/d), ascorbate (290 mg/kg/d), ascorbyl-GLA (790 mg/kg/d),
      or GLA and ascorbate (500 and 290 mg/kg/d, respectively) throughout pregnancy.
      Fetal skeletons were studied after alizarin red staining. Fewer ossification
      centers were observed in offspring of diabetic rats compared with offspring of
      control rats (68 +/- 4% of control, p = 0.01). An almost complete restoration of
      ossification occurred with all the treatments (92-95 +/- 3% of control). The
      effects of treatment on fetal ossification could not be explained by altered
      maternal plasma Ca(2+) concentrations or by mRNA expression of the placental
      Ca(2+)-transporting protein calbindin-D(9K). We conclude that GLA and/or
      ascorbate treatment was effective against diabetes-induced fetal ossification
      defects by a mechanism not related to placental Ca(2+) supply.

PMID- 11978892
TI  - Circulating concentrations of chemokines in cord blood, neonates, and adults.
AB  - Chemokines are critical for the movement of leukocytes. Chemotaxis is deficient
      in neonates, particularly those delivered prematurely, and this likely
      contributes to their increased vulnerability to sepsis. The concentrations of
      circulating chemokines in neonates have not been reported, nor is it known
      whether low chemokine concentrations contribute to their defective chemotaxis. We
      hypothesized that serum concentrations of chemokines 1) would be lower in preterm
      than term neonates, and 2) would be lower in preterm and term neonates than
      adults. Samples were obtained from preterm and term neonates with normal
      neutrophil and eosinophil counts, umbilical cord blood samples from pregnancies
      without clinical evidence of intra-amniotic infection, and healthy adult
      volunteers. The concentrations of epithelial neutrophil activating peptide-78,
      growth-related oncogene-alpha, eotaxin, RANTES (regulated upon activation, normal
      T cell expressed and secreted), and macrophage inflammatory protein-1 alpha were
      measured using specific ELISA. Serum concentrations from preterm infants were
      either similar to or higher than those measured in term neonates and adults. We
      conclude that the chemotactic defect observed in premature neonates is not the
      result of diminished circulating concentrations of any of the specific chemokines
      we measured.

PMID- 11978893
TI  - Absence of the G1528C (E474Q) mutation in the alpha-subunit of the mitochondrial
      trifunctional protein in women with acute fatty liver of pregnancy.
AB  - Acute fatty liver of pregnancy (AFLP) is a rare and dreaded complication of
      pregnancy, almost exclusively seen in the third trimester. The histopathologic
      features of AFLP closely resemble those seen in metabolic disorders characterized
      by deficiency of fatty acid oxidative enzymes. Several reports have established a
      strong association between AFLP in the mother and fetal deficiency of the enzyme
      long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD). However, these studies have
      an inevitable selection bias resulting from ascertainment through an affected
      infant, rather than an unselected population of patients with AFLP. We
      retrospectively examined a series of 10 women with pregnancies complicated by
      AFLP to determine the prevalence of the common LCHAD mutation (G1528C) in this
      population. The existing LCHAD primers, which produce a 640-bp amplicon (IJlst L,
      Ruiter JP, Hoovers JM, Jakobs ME, Wanders RJ: J Clin Invest 98:1028-1033, 1996),
      were modified to make them amenable to analysis of fragmented DNA obtained from
      microdissected formalin-fixed material. None of the patients were found to harbor
      the common G1528C mutation. It is likely that AFLP arising in the context of
      fetal LCHAD deficiency represents only one of the possible etiologies for this
      uncommon disorder, and the metabolic basis of AFLP is more heterogeneous than
      previously believed.

PMID- 11978896
TI  - Autism--what is it and where does it come from?

PMID- 11978894
TI  - Recruitment and development of academic pediatricians: departmental commitments
      to promote success.

PMID- 11978897
TI  - Translational medicine: targetting cyclo-oxygenase isozymes to prevent cancer.

PMID- 11978898
TI  - Oximes in acute organophosphorus pesticide poisoning: a systematic review of
      clinical trials.
AB  - BACKGROUND: Acute organophosphorus (OP) pesticide poisoning is widespread in the
      developing world. Standard treatment involves the administration of intravenous
      atropine and an oxime to counter acetylcholinesterase inhibition at the synapse,
      but the usefulness of oximes is uncertain. AIM: To assess the evidence on the use
      of oximes in OP poisoning. DESIGN: Systematic review. METHODS: We searched
      Medline, Embase, and Cochrane databases (last check 01/02/02) for
      'organophosphate' or 'oxime' together with 'poisoning' or 'overdose'. We cross
      referenced from other articles, and contacted experts to identify unpublished
      studies. A Web search engine [www.google.com] was also used, with the keywords
      'organophosphate', 'oxime', and 'trial' (last check 01/02/02). RESULTS: We found
      two randomized controlled trials (RCTs) involving 182 patients treated with
      pralidoxime. The RCTs found no benefit with pralidoxime, and have been used to
      argue that pralidoxime should not be used in OP poisoning. DISCUSSION: The RCT
      authors must be congratulated for attempting important studies in a difficult
      environment. However, their studies did not take into account recently clarified
      issues regarding outcome, and their methodology is unclear. A generalized
      statement that pralidoxime should not be used in OP poisoning is not supported by
      the published results. Oximes may well be irrelevant in the overwhelming self
      poisoning typical of the tropics, but a large RCT comparing the current WHO
      recommended pralidoxime regimen (>30 mg/kg bolus followed by >8 mg/kg/h infusion)
      with placebo is needed for a definitive answer. Such a study should be designed
      to identify any patient subgroups that might benefit from oximes.

PMID- 11978899
TI  - A pilot study of N-acetylcysteine as adjunctive therapy for severe malaria.
AB  - BACKGROUND: The case fatality rate of severe malaria remains unacceptably high. N
      acetylcysteine (NAC) is a safe compound that inhibits tumour necrosis factor
      (TNF) and impedes cytoadherence, both of which have been implicated in the
      pathogenesis of malaria complications. AIM: To evaluate NAC as adjunctive therapy
      in severe malaria. DESIGN: A placebo-controlled, double-blind prospective study,
      with serum lactate level as the principal objective measure of response. METHODS:
      Thirty adult males with severe, quinine-treated malaria received either 300 mg/kg
      of NAC or placebo, over 20 h. RESULTS: Serum lactate levels normalized twice as
      quickly after NAC (median 21 h, 95%CI 12-36 h) as after placebo (median 42 h,
      95%CI 30-84 h; p=0.002, Mann-Whitney U test). Twenty-four hours after admission,
      10/15 (67%) NAC-group patients but only 3/15 (20%) placebo-group patients had
      normal lactate concentrations (p=0.01, Fisher exact test). NAC-treated patients
      could be switched from intravenous to oral therapy earlier than individuals who
      received placebo (42 h vs. 51 h after admission) but the difference was not
      significant (p=0.28, Mann-Whitney U test). DISCUSSION: NAC's mechanism of action
      in malaria is unclear, since it did not markedly alter plasma cytokine profiles.
      Trials of NAC adjunctive therapy for complicated malaria, with mortality as an
      endpoint, appear to be warranted.

PMID- 11978901
TI  - Establishment and feasibility of community-based general-practitioner-led
      cardiology clinics.
AB  - BACKGROUND: Community-based general practitioner (GP) cardiology clinics
      (locality clinics) offer an alternative to hospital-based cardiology clinics. In
      the Greenwich area, four GPs were trained for 3 months in cardiology, followed by
      another 3 months in a hospital out-patient clinic. GPs then established
      cardiology clinics in their practices and continued to act as hospital clinical
      assistants on an alternate-week basis. AIM: To assess referral and investigation
      patterns for the locality clinics over their first 3 years. DESIGN: Pilot study,
      retrospective case-note audit. METHODS: We analysed 125 sets of notes selected at
      random from the locality and the hospital clinics, and compared them. RESULTS:
      There were no differences in demographics or the indication for referral between
      locality and hospital clinics, and despite the small sample size, no major
      differences in referral and investigation patterns. In both clinics,
      approximately 83% of patients had at least one cardiac investigation, and
      approximately 63% were discharged after initial consultation. Some 10% of
      locality patients were referred for follow-up in the hospital clinic. Beta
      blockers were prescribed more by hospital doctors (14% vs. 3%), with no
      significant difference in other cardiac medications. Coronary risk factors were
      more often recorded in the notes of locality patients. DISCUSSION: Establishing
      community-based GP cardiology clinics seems feasible, and these clinics may be
      the way forward for enhancing cardiac care in the community.

PMID- 11978900
TI  - Risk factors for nephrotoxicity in elderly patients receiving once-daily
      aminoglycosides.
AB  - BACKGROUND: There remain concerns about the safety of once-daily dosing of
      aminoglycosides (AGs) in the elderly. AIM: To assess the safety of once-daily AGs
      in elderly patients and evaluate possible risk factors for nephrotoxicity.
      DESIGN: Prospective, non-interventional surveillance study. METHODS: All patients
      receiving AGs were monitored over 4 months. Clinicians determined the AG dose for
      each patient after estimating patient weight and calculating creatinine clearance
      (CrCl) using the Cockcroft-Gault formula. Parallel figures were calculated by the
      investigators using measured weight. Clinicians obtained an AG trough level 24 h
      after initiation of treatment, and, if non-toxic, every 5-7 days thereafter. AG
      toxicity was defined as an increase in serum creatinine of > or =50%. RESULTS: In
      the study period, 249 consecutive patients received an AG: 116 (47%) males,
      mean+/-SD age 75+/-16 years. Forty-two (17%) received amikacin and 207 (83%)
      gentamicin. An increase of > or =50% in serum creatinine was detected in 31/249
      (12.4%); maximal creatinine was < or =177 micromol/l in 16/249 (6.4%), 186-265
      micromol/l in nine (3.6%), and >265 micromol/l in six (2.4%). None developed
      oliguric renal failure. Renal damage correlated with a high AG trough level (>1.1
      microg/ml) (p<0.001); haemoglobin level <10 g/dl (p<0.05); hospital admission >7
      days prior to AG treatment (p<0.005); and AG treatment > or =11 days (p<0.05).
      Mean CrCl based on estimated weight was 52+/-18 ml/min; that based on actual
      weight was 71+/-37 ml/min. Despite this, mean AG dose was 1.3+/-0.6 higher than
      optimal. CONCLUSIONS: Oliguric and/or lasting renal toxicity is rare in elderly
      patients receiving once-daily aminoglycosides for <11 days, if regular trough
      drug levels are monitored.

PMID- 11978902
TI  - The cost utility of bisphosphonate treatment in established osteoporosis.
AB  - BACKGROUND: Hip fracture is an important and costly problem. Bisphosphonate
      therapy prevents hip and other fractures among women with established
      osteoporosis, but there are few published economic evaluations of this treatment.
      AIM: To assess the cost-effectiveness of risedronate, a recently launched
      bisphosphonate for the prevention of fractures among women with established
      osteoporosis. METHODS: A state transition Markov model of established post
      menopausal osteoporosis based upon randomized clinical trial data was developed.
      Uncertainty underlying model parameters and outcomes was dealt with using
      traditional sensitivity analysis and stochastic sensitivity analysis to produce
      quasi-95%CIs. We focussed on patients aged approximately 75 years, since this
      population most closely matches the randomized controlled trial, and is typical
      of osteoporosis patients in the UK. RESULTS: The baseline model of treating a
      cohort of 1000 75-year-old women for 3 years with risedronate and then modelling
      the costs and benefits over their expected lifetimes, produced net savings of
      pound sterling 786 000 for the treatment group per 1000 treated women, (95%CI
      pound sterling 1.55m savings to pound sterling 47000 extra costs). Restricting
      the horizon of the analysis to only three years led to a small net cost of pound
      sterling 138 000 per 1000 treated women (95%CI pound sterling 196 000 savings to
      pound sterling 477 000 extra costs) with a net increment in Quality Adjusted Life
      years (QALYs) of 16 per 1000 treated women. This resulted in a cost per QALY of
      pound sterling 8625 per treated woman. CONCLUSIONS: In this example, the use of
      risedronate therapy in 75-year-old women at high risk of hip fracture leads to an
      improvement in quality of life with possible cost savings. Restricting the
      analysis to a time horizon of only three years leads to a QALY gain at a modest
      net cost.

PMID- 11978903
TI  - Should patients with lacunar stroke and severe carotid artery stenosis undergo
      endarterectomy?

PMID- 11978904
TI  - Hyponatraemia and hyperglycaemia during laproscopic surgery.
AB  - The aim of this masterclass is to develop a rational plan of therapy to deal with
      a severe degree of hyponatraemia (90 mmol/l) and hyperglycaemia (100 mmol/l) that
      occurred 100 min after the start of laproscopic surgery in a young woman. The
      lavage fluid used in this procedure was 10% dextrose.H(2)O in water (505 mmol
      glucose/l). To focus attention on specific issues, three questions are posed to
      the reader, as they were to a panel of 59 modern-day experts. Two imaginary
      consultants from the past were asked the same (and additional) questions. Their
      responses were restricted to knowledge available before the molecular era, to
      show the power of integrative physiology at the bedside. An analysis of
      intracellular events was helpful in answering the first question: 'Is an infusion
      of hypertonic saline required to treat her acute hyponatremia?' Similarly, a
      quantitative analysis of changes in the composition of the extracellular fluid
      compartment was helpful in answering the second question: 'Is an infusion of
      isotonic saline required to treat her hypotension?' A metabolic analysis was used
      to answer the third question, 'Should insulin be administered?'

PMID- 11978905
TI  - Determinants of size at birth.

PMID- 11978907
TI  - Technophobia.

PMID- 11978906
TI  - Pyrin Q148 mutation and familial Mediterranean fever.

PMID- 11978908
TI  - A house divided.

PMID- 11978909
TI  - Candidate gene studies in respiratory disease: avoiding the pitfalls.

PMID- 11978910
TI  - Age at childhood infections and risk of atopy.
AB  - BACKGROUND: It has been proposed that early age at exposure to common childhood
      infections is associated with a decreased risk of allergy. Previous studies on
      the possible association between allergy and infection with measles, mumps,
      rubella, and varicella have not been conclusive as most did not include
      information on exact age at exposure. The objective of our study was to
      investigate whether early age at exposure to these infections was associated with
      a decreased risk of atopy using information on exact age at infection. METHODS:
      The study population consisted of 889 pregnant women who participated in a
      national birth cohort study in Denmark and for whom detailed information on
      history of measles, rubella, varicella, and mumps before school entry (age 7
      years) was available from school health records from Copenhagen. Atopic status
      was assessed serologically by a specific response to 11 common inhalant allergens
      using serum samples obtained from the women during pregnancy. RESULTS: Measles in
      the first year of life was associated with a higher risk of atopy than no measles
      before age 7 years (OR 3.36, 95% CI 1.47 to 7.68). There was no association
      between atopy and mumps, rubella, or varicella in the first 7 years of life or
      with measles acquired after the first year of life. The risk of atopy increased
      significantly with increasing number of childhood infections in the first 2 years
      of life (p(trend)=0.01). CONCLUSIONS: These findings do not support the
      suggestion that childhood exposure to measles, rubella, varicella, or mumps
      protects against atopy, even if acquired very early in life.

PMID- 11978911
TI  - Exhaled nitric oxide correlates with airway eosinophils in childhood asthma.
AB  - BACKGROUND: Exhaled nitric oxide has been proposed as a marker for airway
      inflammation in asthma. The aim of this study was to compare exhaled nitric oxide
      levels with inflammatory cells and mediators in bronchoalveolar lavage fluid from
      asthmatic and normal children. METHODS: Children were recruited from elective
      surgical lists and a non-bronchoscopic bronchoalveolar lavage (BAL) was performed
      after induction of anaesthesia. Exhaled nitric oxide (parts per billion) was
      measured by two techniques: tidal breathing and restricted breath. RESULTS:
      Median (interquartile range) exhaled nitric oxide measured by restricted breath
      was increased in asthmatics compared with normal children (24.3 (10.5-66.5) v 9.7
      (6.5-16.5), difference between medians 14.6 (95% CI 5.1 to 29.9), p=0.001). In
      asthmatic children exhaled nitric oxide correlated significantly with percentage
      eosinophils (r=0.78, p<0.001 (tidal breathing) and r=0.78, p<0.001 (restricted
      breath)) and with eosinophilic cationic protein (r=0.53, p<0.01 (restricted
      breath)), but not with other inflammatory cells in the BAL fluid. The area under
      the receiver operator characteristic curves for the prediction of the presence of
      eosinophilic airways inflammation by exhaled nitric oxide (tidal and restricted)
      was 0.80 and 0.87, respectively. CONCLUSIONS: Exhaled nitric oxide correlates
      closely with percentage eosinophils in BAL fluid in asthmatic children and is
      therefore likely to be a useful non-invasive marker of airway inflammation.

PMID- 11978912
TI  - Lung function at one month of age as a risk factor for infant respiratory
      symptoms in a high risk population.
AB  - BACKGROUND: Abnormal premorbid lung function is a risk factor for subsequent
      wheezing in children with one or no atopic parent. This study was undertaken to
      establish whether early lung function in high risk infants (both parents atopic)
      was a risk factor for respiratory symptoms in infancy and to examine the
      influence of maternal asthma, smoking, and allergen exposure during pregnancy on
      any association. METHODS: Infants were recruited from the NAC Manchester Asthma
      and Allergy Study cohort at birth. Partial forced expiratory flow volume
      technique under sedation was carried out to determine maximal flow at FRC
      (V'maxFRC). Children were followed prospectively and parents completed a standard
      respiratory questionnaire at one year of age. RESULTS: Sixty nine term infants
      (34 boys; 88% mothers non-smokers; no household pets) underwent respiratory
      function testing. Size adjusted V'maxFRC was significantly lower in infants who
      had recurrent wheeze during the first year of life (mean 1.3 ml/s/cm, 95% CI 0.99
      to 1.60) than in those who did not (mean 2.03 ml/s/cm, 95% CI 1.71 to 2.36;
      p=0.01). V'maxFRC was also significantly lower in infants who had recurrent cough
      symptoms. In multivariate regression analysis, when adjusted for age at test,
      sex, maternal asthma, smoking and maternal mattress Der 1 levels, a lower size
      adjusted V'maxFRC score remained strongly associated with wheezing (OR 0.37, 95%
      CI 0.18 to 0.77, p=0.007). Maternal smoking also remained an independent risk
      factor (OR 29.85, 95% CI 2.46 to 362.5, p=0.008). CONCLUSION: Significantly
      diminished lung function was present in high risk infants who subsequently
      wheezed and coughed. This was independent of maternal exposure to mite allergen,
      asthma, and smoking during pregnancy.

PMID- 11978913
TI  - Comparing and combining studies of bronchial responsiveness.
AB  - BACKGROUND: There is no standardised protocol for the measurement of bronchial
      responsiveness. Results from different studies are difficult to compare and
      combine. METHODS: Analyses are divided between those of a continuous outcome,
      which can be directly standardised as effect size, and those based on a binary
      outcome. A published method is used to convert an odds ratio to equivalent effect
      size. RESULTS: The use of effect size allows comparison between studies using a
      continuous outcome but different protocols, provided the relevant standard
      deviation is reported. Effect size from a continuous outcome and that derived
      from an odds ratio from an equivalent analysis gave similar results. CONCLUSIONS:
      Systematic reviews which include both continuous effect estimates and odds ratios
      can include both in one meta-analysis, provided relevant standard deviations are
      published for the former. Authors are encouraged to report these in all fields in
      which measurement protocols vary.

PMID- 11978914
TI  - Contribution of nasal pathways to low frequency respiratory impedance in infants.
AB  - BACKGROUND: In infants the impedance of the nasal pathways (Zn) is a significant
      proportion of the total respiratory impedance (Zrs). METHODS: In 11 infants Zrs
      was partitioned into Zn and lower respiratory system impedance (Zlrs) using a
      nasal catheter. A low frequency oscillatory signal (0.5-20 Hz) was applied during
      a pause in breathing to obtain the impedance spectra. A model of the respiratory
      system containing an airway and tissue compartment was then fitted to Zrs and
      Zlrs. The airway compartment consisted of a frequency independent resistance (R)
      and inertance (I), while the tissue compartment was described by coefficients of
      tissue damping (G) and elastance (H). RESULTS: Zrs could be reliably partitioned
      into Zn and Zlrs. The nasal pathway acted as a purely resistive-inertive
      impedance and contributed approximately half of the airway resistance (mean (SE)
      44.6 (4.9)%) and most of the respiratory system inertance (71.7 (3.5)%).
      CONCLUSIONS: In studies investigating changes in airway resistance in nasally
      breathing infants, the separation of nasal and lower respiratory system mechanics
      will increase the sensitivity of the tests.

PMID- 11978915
TI  - Increased resting bronchial tone in normal subjects acclimatised to altitude.
AB  - BACKGROUND: Normal subjects frequently experience troublesome respiratory
      symptoms when acclimatised to altitude. Bronchial hyperresponsiveness (BHR) and
      full and partial flow-volume loops were measured before and after ascent to 5000
      m altitude to determine if there are changes in resting bronchial tone and BHR
      that might explain the symptoms. METHODS: BHR to histamine was measured using a
      turbine spirometer to record partial and full flow-volume curves and expressed as
      log dose slopes. Twenty one subjects were tested at sea level and after
      acclimatisation at 5000 m altitude. RESULTS: No significant change in log dose
      slope measurements of forced expiratory volume in 1 second occurred after
      acclimatisation, and the maximal expiratory flow with 30% of forced vital
      capacity remaining (MEF(30%)) rose on the full loop and fell on the partial loop.
      Their ratio (full divided by partial) rose on average by 0.28 (95% confidence
      limits 0.14 to 0.42) from the mean (SD) sea level value of 0.87 (0.20).
      CONCLUSIONS: There is no increase in BHR in normal subjects acclimatised to
      altitude but an increase in resting bronchial tone occurs that could be released
      by deep inspiration. This may be the result of increased cholinergic tone.

PMID- 11978916
TI  - Increased levels of interleukin-8 in BAL fluid from smokers susceptible to
      pulmonary emphysema.
AB  - BACKGROUND: It has previously been shown that smokers with computed tomographic
      (CT) evidence of subclinical emphysema have signs of neutrophil activation,
      despite having no appreciable increase in the number of neutrophils in their
      bronchoalveolar lavage (BAL) fluid. METHODS: The levels of the following
      chemoattractants in BAL fluid from 61 community based older volunteers classified
      into four groups according to current smoking status and the presence or absence
      of emphysema were determined: interleukin 8 (IL-8), epithelial neutrophil
      activating protein 78 (ENA-78) and leukotriene B(4) (LTB(4)) which are primarily
      chemotactic for neutrophils; monocyte chemoattractant protein 1 (MCP-1) and
      macrophage inflammatory protein-1alpha (MIP-1alpha) which are predominantly
      chemotactic for mononuclear leucocytes. RESULTS: Of the five chemoattractants
      studied, only the level of IL-8 in BAL fluid clearly distinguished between
      subjects with and without emphysema among current smokers (median values 34.7 and
      12.2 pg/ml, respectively, p<0.01). In addition, the levels of IL-8 and neutrophil
      elastase-alpha(1) protease inhibitor complex in BAL fluid were significantly
      correlated (r=0.65, p<0.01). There was no difference in either the release of IL
      8 from cultured alveolar macrophages at 24 hours or the expression of IL-8
      messenger RNA of alveolar macrophages in the two groups of current smokers with
      and without emphysema. CONCLUSION: An accelerated response of IL-8 to chronic
      smoking is a factor that characterises those smokers who are susceptible to
      pulmonary emphysema, although the cellular source of IL-8 remains to be
      determined.

PMID- 11978917
TI  - Risk of depression in patients with chronic obstructive pulmonary disease and its
      determinants.
AB  - BACKGROUND: Although it has been repeatedly suggested that chronic obstructive
      pulmonary disease (COPD) is associated with depression, no conclusion has so far
      been reached. A study was undertaken to investigate whether depression occurs
      more often in patients with COPD than in controls. The demographic and clinical
      variables associated with depression were also determined. METHODS: Patients with
      a registered diagnosis of obstructive airway disease in general practice, aged >
      or=40 years, forced expiratory volume in 1 second (FEV(1)) <80% predicted, FEV(1)
      reversibility <or =12%, FEV(1)/VC < or = predicted - 1.64 x SD, and a history of
      smoking were selected. A random sample of subjects without a registered diagnosis
      of asthma or COPD aged 40 years or older acted as controls. Depression was
      assessed using the Centers for Epidemiologic Studies Depression (CES-D) scale.
      RESULTS: In patients with severe COPD (FEV(1) <50% predicted), the prevalence of
      depression was 25.0% compared with 17.5% in controls and 19.6% in patients with
      mild to moderate COPD. When the results were adjusted for demographic variables
      and comorbidity, the risk for depression was 2.5 times greater for patients with
      severe COPD than for controls (OR 2.5, 95% CI 1.2 to 5.4). In patients with mild
      to moderate COPD this increased risk of depression was not seen. Living alone,
      reversibility of FEV(1) % predicted, respiratory symptoms and physical impairment
      were significantly associated with the scores on the CES-D scale. CONCLUSION:
      Patients with severe COPD are at increased risk of developing depression. The
      results of this study underscore the importance of reducing symptoms and
      improving physical functioning in patients with COPD.

PMID- 11978918
TI  - Cardiovascular medication use in patients with undiagnosed obstructive sleep
      apnoea.
AB  - BACKGROUND: A study was undertaken in patients with undiagnosed sleep
      apnoea/hypopnoea syndrome (OSAS) to document the use of prescribed medications,
      especially those used in cardiovascular diseases, in the year before the OSAS
      diagnosis was confirmed. METHODS: A total of 549 patients with OSAS (401 men of
      mean age 47.2 years, mean body mass index (BMI) 35.5 kg/m(2), mean
      apnoea/hypopnoea index (AHI) 47.2 and148 women of mean age 50.2 years, BMI 39.6
      kg/m(2), AHI 32.6) were each matched to one general population control by age,
      sex, geographical location, and family physician. Medication use was evaluated
      for patients and controls using a database containing information about all
      prescriptions completed in the province of Manitoba, Canada. RESULTS: In the year
      before OSAS was diagnosed, prescribed medication costs were $155.91 (Canadian
      dollars) (95% CI $91.34 to $220.49) greater for cases than for controls. Cases
      were dispensed 3.3 (95% CI 1.5 to 5.2) more prescriptions, were on 1.2 (95% CI
      0.8 to 1.6) more medications, and were supplied with 157.4 (95% CI 95.9 to 218.8)
      more daily doses of medication. The odds ratio of OSAS cases being on a
      prescribed medication was 1.88 relative to controls (95% CI 1.38 to 2.54,
      p<0.0001). In the same year 36.6% of cases and 19.7% of controls were using
      medications for cardiovascular disease (OR 2.82, 95% CI 2.05 to 3.89, p<0.0001),
      consuming 79.4 (95% CI 48.9 to 109.8) more daily doses of medication, having been
      dispensed 1.7 (95% CI 1.0 to 2.4) more prescriptions, and at a $75.26 (95% CI
      $44.03 to $106.50) greater cost. The odds ratio of patients with OSAS being on
      medications indicated for the treatment of systemic hypertension was 2.71 (95% CI
      1.96 to 3.77) relative to controls; however, such medications might also be
      prescribed for other indications such as angina pectoris and congestive heart
      failure, and for the secondary prevention of myocardial infarction. The use of
      medications indicated for the treatment of systemic hypertension was predicted
      significantly by age (odds ratio (OR) 1.10 per year), BMI (OR 1.05 per unit), and
      AHI (OR 1.01 per unit). CONCLUSIONS: In the year before OSAS was diagnosed,
      patients with OSAS were heavy users of medications, particularly those used to
      treat cardiovascular diseases.

PMID- 11978919
TI  - Evidence for expiratory flow limitation of extrathoracic origin in patients with
      obstructive sleep apnoea.
AB  - BACKGROUND: A study was undertaken to examine the expiratory flow response to a
      negative pressure (NEP) applied at the airway in patients with no abnormalities
      of the intrathoracic airway but suffering from the obstructive sleep apnoea
      syndrome (OSAS). METHODS: Nineteen patients with OSAS with normal spirometric
      values were studied. NEP of -5 cm H(2)O and -10 cm H(2)O was applied to the mouth
      when sitting and when supine. RESULTS: Thirteen patients exhibited expiratory
      flow limitation when supine (group 1). Of these, three also had flow limitation
      in the sitting position. The remaining six patients (group 2) had no flow
      limitation. Patients in groups 1 and 2 were similar with respect to age, sex, and
      body mass index, but the apnoea/hypopnoea index (AHI) was higher in group 1 than
      in group 2 (p<0.05). There was a significant correlation between the degree of
      flow limitation (expressed as a percentage of the expired tidal volume over which
      the NEP induced flow did not exceed spontaneous flow) and the AHI (p<0.05 for
      both pressure levels) as well as the desaturation index (DI, number of
      desaturations per hour of sleep; p<0.05 at -10 cm H(2)O). CONCLUSION: This study
      confirms that the NEP technique can detect expiratory flow limitation of
      extrathoracic as well as of intrathoracic origin. This technique could be useful
      for studying the collapsibility of the passive upper airway in awake subjects and
      might help to predict the severity of OSAS.

PMID- 11978921
TI  - Granulomatous Pneumocystis carinii pneumonia in patients with malignancy.
AB  - BACKGROUND: A review was undertaken of the clinical features and results of
      diagnostic tests in non-HIV infected patients who developed granulomatous
      Pneumocystis carinii pneumonia (PCP). METHODS: A retrospective review was
      performed of the charts and radiographs of patients with a granulomatous reaction
      to P carinii identified from computerised pathology records at Memorial Sloan
      Kettering Cancer Center, a university affiliated tertiary care hospital. RESULTS:
      Three cases were identified; the incidence of granulomatous PCP was 3%. All
      patients had risk factors for PCP and had received high dose corticosteroids
      which had been stopped. Two patients had received chemotherapy. Presentation was
      insidious with only mild symptoms; only one patient had fever. Chest radiographs
      showed a reticulonodular pattern. Bronchoscopy was negative for PCP in all cases
      and open lung biopsy was necessary. CONCLUSION: A granulomatous pathological
      reaction to PCP occurs rarely in patients with malignancy. In these cases the
      clinical presentation may be atypical and bronchoscopy can be non-diagnostic.

PMID- 11978920
TI  - Plasma leptin levels and cardiac sympathetic function in patients with
      obstructive sleep apnoea-hypopnoea syndrome.
AB  - BACKGROUND: The control of body weight and cardiac sympathetic function in
      patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) are important
      because both factors have significant effects on the mortality of these patients.
      It has recently been reported that OSAHS has a significant effect on the
      secretion of leptin, a hormone involved in the control of body weight and
      sympathetic nerve activity. In addition to the circadian rhythm of leptin
      secretion, the effects of one night of treatment with nasal continuous positive
      airway pressure (nCPAP) and the mechanism of the effects of nCPAP on nocturnal
      leptin secretion in patients with OSAHS has not yet been elucidated. METHODS:
      Blood samples were obtained at 21.00 hours, 00.00 hours, 03.00 hours, and 06.30
      hours from 21 subjects with OSAHS (mean apnoea and hypopnoea index 52.4/h), with
      and without nCPAP treatment. Iodine-123 (I(123))-meta-iodobenzylguanidine (MIBG)
      imaging was used to evaluate myocardial sympathetic function before nCPAP
      treatment. RESULTS: Plasma leptin reached a peak level at 00:00 hours (p<0.01) in
      patients with OSAHS, both with and without nCPAP treatment. The first night of
      nCPAP treatment significantly decreased the plasma leptin levels at 03.00 hours
      (without nCPAP: mean (SE) 21.6 (4.7) ng/ml; with nCPAP: 19.3 (4.1) ng/ml, p<0.02)
      and at 06.30 hours (without nCPAP: 17.6 (3.8) ng/ml; with nCPAP: 15.2 (3.2)
      ng/ml, p<0.01). The magnitude of the decrease in leptin levels after nCPAP
      treatment was significantly correlated with cardiac sympathetic function measured
      before nCPAP treatment (p<0.03). CONCLUSIONS: Patients with OSAHS undergo
      nocturnal increases in leptin levels in spite of interruption of sleep due to
      apnoea and hypopnoea, a trend seen in normal subjects. Plasma leptin levels in
      patients with OSAHS decreased significantly after the first night of nCPAP
      treatment. Enhanced cardiac sympathetic function in these patients may contribute
      to the leptin levels before nCPAP treatment and vice versa.

PMID- 11978923
TI  - An estimate of the contribution of HIV infection to the recent rise in
      tuberculosis in England and Wales.
AB  - BACKGROUND: The number of patients with tuberculosis has been increasing slowly
      in England and Wales since the late 1980s. HIV infection has been a contributory
      factor to increases in tuberculosis in a number of comparable industrialised
      countries. This study investigated the extent of tuberculosis and HIV co
      infection in England and Wales in 1993 and 1998, and estimated its contribution
      to the increase in tuberculosis observed during this period. METHODS: Patients
      aged 16-54 years old at diagnosis on the 1993 and 1998 National Tuberculosis
      Survey databases were matched with those on the HIV/AIDS patient database. A
      coded process maintained patient confidentiality. Primary outcome measures were
      the increase between 1993 and 1998 in the numbers with both infections reported
      and an estimate of the proportion of the increase in tuberculosis during this
      period attributable to HIV co-infection. RESULTS: In 1993 61 (2.2%) tuberculosis
      patients aged 16-54 years matched with patients reported to the HIV database,
      increasing to 112 (3.3%) in 1998 (p=0.08; OR 1.35; 95% CI 0.97 to 1.87). Patients
      co-infected with HIV contributed an estimated 8.5% of the increase in number of
      tuberculosis patients between 1993 and 1998 nationwide (11% in London). In both
      years prevalence of co-infection was greatest in London and in patients of white
      and black African ethnic groups. CONCLUSIONS: In 1998 the number of tuberculosis
      patients co-infected with HIV in England and Wales, though still small, had
      nearly doubled since 1993, with most of the increase occurring in London. As HIV
      infection may be undiagnosed in patients with tuberculosis, and tuberculosis may
      be unreported in patients with diagnosed HIV infection, the true extent of co
      infection will have been underestimated by this study. In addition, constraints
      in coded matching make it inevitable that some reported co-infections are missed.
      Routine HIV testing of all patients with tuberculosis should now be considered,
      particularly in patients of white or black African ethnic origin under 55 years
      of age.

PMID- 11978922
TI  - Differentiation of bacterial and viral pneumonia in children.
AB  - BACKGROUND: A study was undertaken to investigate the differential diagnostic
      role of chest radiographic findings, total white blood cell count (WBC),
      erythrocyte sedimentation rate (ESR), and serum C reactive protein (CRP) in
      children with community acquired pneumonia of varying aetiology. METHODS: The
      study population consisted of 254 consecutive children admitted to hospital with
      community acquired pneumonia diagnosed between 1993 and 1995. WBC, ESR, and CRP
      levels were determined on admission. Seventeen infective agents (10 viruses and
      seven bacteria) were searched for. Chest radiographs were retrospectively and
      separately reviewed by three paediatric radiologists. RESULTS: A potential
      causative agent was found in 215 (85%) of the 254 cases. Bacterial infection was
      found in 71% of 137 children with alveolar infiltrates on the chest radiograph,
      while 72% of the 134 cases with a bacterial pneumonia had alveolar infiltrates.
      Half of the 77 children with solely interstitial infiltrates on the chest
      radiograph had evidence of bacterial infection. The proportion of patients with
      increased WBC or ESR did not differ between bacterial and viral pneumonias, but
      differences in the CRP levels of >40 mg/l, >80 mg/l, and >120 mg/l were
      significant although the sensitivity for detecting bacterial pneumonia was too
      low for use in clinical practice. CONCLUSIONS: Most children with alveolar
      pneumonia, especially those with lobar infiltrates, have laboratory evidence of a
      bacterial infection. Interstitial infiltrates are seen in both viral and
      bacterial pneumonias.

PMID- 11978924
TI  - Randomised crossover study of the Flutter device and the active cycle of
      breathing technique in non-cystic fibrosis bronchiectasis.
AB  - BACKGROUND: Airway clearance techniques are an important part of the routine care
      of patients with bronchiectasis. The use of the Flutter, a hand held pipe-like
      device causing oscillating positive expiratory pressure within the airways, has
      been proposed as an alternative to more conventional airway clearance techniques.
      METHODS: A randomised crossover study was performed in 17 stable patients with
      non-cystic fibrosis bronchiectasis at home, in which 4 weeks of daily active
      cycle of breathing technique (ACBT) were compared with 4 weeks of daily
      physiotherapy with the Flutter device. RESULTS: No significant differences
      between the two techniques were found. Median weekly sputum weights were similar
      with a median treatment difference of 7.64 g (p=0.77) and there was no evidence
      of treatment order or order interaction effects (p=0.70). Health status (Chronic
      Respiratory Disease Questionnaire) and ventilatory function did not change
      significantly during either treatment period. There was no significant change in
      peak expiratory flow rate or in breathlessness (Borg score) after individual
      physiotherapy sessions with either technique. A questionnaire indicated
      subjectively that patients preferred the Flutter (11/17) to ACBT for routine use.
      CONCLUSIONS: Daily use of the Flutter device in the home is as effective as ACBT
      in patients with non-cystic fibrosis bronchiectasis, and has a high level of
      patient acceptability.

PMID- 11978925
TI  - Cell specific markers for eosinophils and neutrophils in sputum and
      bronchoalveolar lavage fluid of patients with respiratory conditions and healthy
      subjects.
AB  - BACKGROUND: Highly specific protein markers for eosinophils and neutrophils could
      be a valuable diagnostic aid in various respiratory disorders. The cell
      specificity of monoclonal antibodies against eosinophil peroxidase (EPO),
      eosinophil cationic protein (ECP), human neutrophil lipocalin (HNL), and
      myeloperoxidase (MPO) was investigated using immunocytochemical techniques.
      METHODS: Induced sputum and bronchoalveolar lavage fluid samples from 14 patients
      with respiratory conditions and four healthy individuals were studied. Antigens
      were detected at their intracellular sites in cells with well preserved
      structures using optimal techniques for fixation, permeabilisation, and
      immunolabelling. RESULTS: Anti-EPO antibodies reacted only with eosinophils, and
      anti-HNL antibodies only with neutrophils. Anti-ECP antibodies reacted with both
      eosinophils and neutrophils and anti-MPO antibodies with neutrophils and
      monocytes. Cells not stained by monoclonal anti-EPO and anti-HNL antibodies
      included lymphocytes, monocytes, macrophages, squamous epithelial cells, and
      ciliated epithelial cells. CONCLUSIONS: EPO, a unique component of eosinophils,
      and HNL, a unique component of neutrophils, are useful markers for the
      identification of eosinophils and neutrophils, respectively, in sputum and
      bronchoalveolar lavage fluid.

PMID- 11978926
TI  - The pulmonary physician in critical care. 5: Acute lung injury and the acute
      respiratory distress syndrome: definitions and epidemiology.
AB  - An understanding of the epidemiology of ALI/ARDS and the effects of treatment
      have been hampered by the lack of a uniform definition of the syndrome. Various
      definitions have been proposed, and these are reviewed with particular attention
      to how changes in definition have affected our understanding of the natural
      history and treatment options for the condition.

PMID- 11978927
TI  - Determinants of adherence in adults with cystic fibrosis.
AB  - Cystic fibrosis (CF) is now as much a disease of adults as of children and
      adolescents. An important focus of recent research has been the impact of the
      complex, expensive, and time consuming routine of self-care and medical treatment
      that is required by adults with CF to maintain health. A growing concern for
      medical and allied health teams is the issue of patient adherence to prescribed
      health management plans. A summary of the particular medical and treatment
      context of CF is followed by a review of adherence measurement issues and the
      determinants of adherence to treatment regimens in people with CF, primarily
      adults. Evidence for factors which influence adherence decisions of people with
      CF is examined. The medical and psychological aspects of this complex problem
      have not been adequately addressed because of difficulties with definition and
      measurement. Only a small proportion of the variance in adherence has been
      accounted for in the literature. New measurement technologies and new theoretical
      directions offer promise for a better understanding of this complex and important
      issue and may result in more effective intervention strategies to improve
      adherence.

PMID- 11978928
TI  - Migratory pulmonary infiltrates in a patient with rheumatoid arthritis.
AB  - The case history is described of an elderly man with rheumatoid arthritis
      receiving treatment with sulfasalazine and the cyclooxygenase-2 inhibitor
      celecoxib who presented with severe shortness of breath, cough, and decreased
      exercise tolerance. The chest radiograph showed unilateral alveolo-interstitial
      infiltrates and a biopsy specimen of the lung parenchyma showed changes
      consistent with acute eosinophilic pneumonia. Antibiotic treatment was
      unsuccessful, but treatment with steroids and discontinuation of sulfasalazine
      and celecoxib resulted in a marked clinical improvement confirmed by arterial
      blood gas analysis. The condition may have developed as an adverse reaction
      either to sulfasalazine or to celecoxib, although hypersensitivity to the latter
      has not previously been reported.

PMID- 11978929
TI  - Pulmonary rehabilitation.

PMID- 11978930
TI  - Wasting as predictor of survival in CF.

PMID- 11978931
TI  - Embolisation in Behcet's disease.

PMID- 11978932
TI  - Respiratory disease and proximity to coke works.

PMID- 11978934
TI  - Immune-mediated complications during interferon therapy in hematological
      patients.
AB  - Interferon (IFN), a leukocyte-derived cytokine, has been used to treat several
      hematological malignancies. The most common adverse effects of IFN are flu-like
      symptoms. Autoimmune side effects are infrequent but may be hazardous and
      irreversible. These may occur in several ways: autoantibodies may either appear
      during the treatment or existing titers may rise, subclinical autoimmune
      phenomena may become clinically manifest or autoimmune diseases may appear de
      novo. The main categories of IFN immune-mediated side effects are: thyroid,
      hematological, connective tissue, renal and miscellaneous disorders. The most
      common ones are thyroid disorders, which manifest either as hypo- or
      hyperthyroidism. Patients with pre-existing autoantibodies are more susceptible
      to the exacerbation of thyroid autoimmunity, probably since IFN enhances the
      levels of autoimmunity. Hematological disorders include autoimmune anemia and
      thrombocytopenia and thrombotic thrombocytopenic purpura. The immunological
      derangement of autoimmune hemolytic anemia manifests as enhanced destruction of
      antibody-coated red blood cells and induction of autoreactive B cells secreting
      these antibodies. Although autoimmune thrombocytopenia is rare, a sharp reduction
      in the platelet counts, beyond that expected from the antiproliferative effects
      of IFN, should raise this possibility. Thrombotic thrombocytopenic purpura has
      recently been included among the autoimmune disorders. Sporadic cases have been
      reported in association with IFN treatment. The clinical spectrum of IFN-induced
      connective tissue disorders ranges from typical systemic lupus erythematosus to
      seropositive or seronegative rheumatoid arthritis. Some authors also reported on
      the development of Behcet's disease in chronic myeloid leukemia patients treated
      with IFN. The underlying reason for the skin hyperreactivity in Behcet's disease
      and the effect of IFN treatment in these patients may be altered neutrophil
      activity in both disorders. Several series evaluated the incidence of Raynaud's
      phenomenon in patients treated with IFN for hematological disorders. Some of them
      reported on a rather high incidence of nailfold capillary microscopy
      abnormalities with or without Raynaud's phenomenon. Whether IFN-induced Raynaud's
      phenomenon is immune-mediated or directly caused vasospasm, is still unknown
      although the occurrence of several autoantibodies suggests an immune mechanism.
      Adverse effects of IFN therapy on the kidney include proteinuria and rarely
      nephrotic syndrome or acute and chronic renal failure. The mechanism of renal
      injury is unclear although an immune mechanism is suggested. Sporadic cases of
      other immune-mediated side effects have been published. These include
      dermatological adverse effects manifesting as psoriasis, pemphigus and vitiligo,
      and also rare cases of sarcoidosis, hepatitis, colitis or cryoglobulinemia. In
      conclusion, patients treated with IFN should be monitored for symptoms of
      autoimmunity. Patients with previous autoimmune phenomena should be treated, if
      possible, with alternative drugs since there is risk of exacerbation of these
      manifestations in these patients.

PMID- 11978935
TI  - Relationship of body iron stores to levels of serum ferritin, serum iron,
      unsaturated iron binding capacity and transferrin saturation in patients with
      iron storage disease.
AB  - None of the methods for assessing total body iron burden in patients with
      hemochromatosis is satisfactory. Although it is commonly believed that a
      relationship exists between serum ferritin levels and total iron burden, the
      extent of this relationship has not previously been documented. In the present
      investigation we measured the total body iron burden of 88 patients with putative
      hemochromatosis, 54 of whom were homozygotes for the 845G-->A (C282Y) mutation.
      The total body iron stores were estimated from the volume of red cells removed
      during therapeutic phlebotomy corrected for an estimated 2 mg/day dietary iron
      absorbed during the phlebotomy period; the amount of storage iron was compared to
      the serum ferritin, serum iron, unsaturated iron binding capacity, and
      transferrin saturation before the beginning of phlebotomy. The serum ferritin
      proved to be the best predictor of body iron stores. The correlation between all
      of the analytes and the body iron burden was greater in patients homozygous for
      the C282Y mutation than in those who were not, including the compound
      heterozygotes for C282Y and H63D. The body iron burden tended to be greater in
      patients homozygous for the C282Y mutation than the other patients at any other
      given ferritin level. We conclude that the serum ferritin level does provide some
      information regarding total iron burden but even in the case of C282Y
      homozygotes, the correlation is not very strong.

PMID- 11978936
TI  - Impact of thalassemia major on patients and their families.
AB  - OBJECTIVE: To describe the burden of thalassemia major and its treatment, in
      terms of prevalence of iron-overload-related complications, direct and indirect
      costs, and the patient's physical and social well-being. METHODS: From October
      1999 to May 2000 a survey of patients with thalassemia major was conducted in ten
      countries: Cyprus, Egypt, Greece, Hong Kong, India, Iran, Italy, Jordan, Taiwan,
      and the United States. RESULTS: 1,888 questionnaires (65%) were returned. The
      responses suggest that nowadays patients begin blood transfusions, and most use
      desferrioxamine (84.8%), but iron-related complications, including life
      threatening ones such as heart disease, are still common. CONCLUSIONS: There
      remains a need to improve the management of thalassemia, as many patients with
      iron-related complications experience physical and social limitations.

PMID- 11978938
TI  - Intracardiac thrombus in a patient with autoimmune hemolytic anemia leading to a
      diagnosis of antiphospholipid syndrome.
AB  - We report a case of antiphospholipid syndrome (APS) which presented with clinical
      and laboratory signs of an autoimmune hemolytic anemia (AHA), in the absence of
      manifestations typically related to APS. The diagnosis of APS was made only after
      the occurrence of a sudden severe heart failure due to an intraventricular
      thrombus requiring a surgical approach. An accurate thrombophilic screening is
      warranted also in patients with apparently idiopathic AHA.

PMID- 11978937
TI  - Management of essential thrombocythemia during pregnancy with aspirin, interferon
      alpha-2a and no treatment. A comparative analysis of the literature.
AB  - It is advisable to treat essential thrombocythemia (ET) during pregnancy, because
      elevated platelet counts can lead to maternal and fetal complications. In order
      to establish which therapy is more favorable, we undertook a review of the
      literature. In addition to our own case, we found 27 reports which described 75
      cases with 143 pregnancies. We discussed the complications of ET during pregnancy
      and postpartum, fetal outcome and the therapeutic strategies. Considering the
      clear risk of complications during pregnancy -- especially the occurrence of
      spontaneous abortion in the first trimester -- and the risk of intrauterine fetal
      death, we believe all patients should at least be treated with aspirin unless
      there is a contraindication. Platelet reduction with interferon-alpha (IFN-alpha)
      might be able to further reduce the complications of ET during pregnancy and to
      improve fetal outcome (data from 14 patients). After treatment with IFN-alpha,
      sufficient numbers of umbilical cord blood stem cells can be collected.

PMID- 11978940
TI  - Remission induction of refractory anaemia with excess blasts in transformation by
      sole treatment with granulocyte colony-stimulating factor with persistent
      chromosomal abnormality.
AB  - We report a patient with myelodysplastic syndrome (MDS), refractory anaemia with
      excess blasts in transformation, in whom complete remission (CR) was achieved
      with the administration of granulocyte colony-stimulating factor (G-CSF). The 76
      year-old patient was admitted to our hospital with a fever and a productive
      cough; a diagnosis of pneumonia was thus made. Following treatment with
      antibiotics, the patient's condition improved, and MDS was diagnosed from
      peripheral blood and bone marrow examinations after the patient recovered from
      the infection. The patient achieved a sustained haematological CR that was
      confirmed by morphological and flow cytometric examination after treatment with G
      CSF alone, although chromosomal abnormalities persisted. According to the
      literature, in almost all patients with acute myeloid leukaemia or MDS who were
      reported to achieve CR by G-CSF, the course was associated with infection,
      although our case did not have this complication during the course of G-CSF
      therapy. We suggest that patients with G-CSF alone without infection can achieve
      CR and that this may be related to a differentiation effect of G-CSF based on
      persistent chromosomal abnormality in this case.

PMID- 11978939
TI  - Idiopathic myelofibrosis with nodal, serosal and parenchymatous infiltration.
      Case report and review of the literature.
AB  - Idiopathic myelofibrosis (IMF) is a breakpoint cluster region rearrangement
      negative chronic myeloproliferative disease with progressive bone marrow
      fibrosis. We report a female patient (65 years old) who was admitted to our
      hospital in 1996. Trephine bone marrow biopsy revealed diffuse fibrosis with
      atypical multilobulated megakaryocytes. A cellular phase of IMF was diagnosed.
      Three years later, despite being at intermediate risk, the patient developed
      generalized lymphadenopathy and multiple sclerosing tumors throughout the
      peritoneum and retroperitoneum. Biopsy specimens from these tumors revealed
      sclerosing hematopoietic infiltrates. The present case demonstrates that IMF not
      only can progress to acute leukemia but can also spread uncontrollably, or
      'metastasize' with extensive sclerosing hematopoietic tumors throughout the body.

PMID- 11978941
TI  - A rapid spectrophotometric screening assay for paroxysmal nocturnal
      hemoglobinuria.

PMID- 11978942
TI  - Neurotoxicity with leukoencephalopathy after a single intravenous high dose of
      methotrexate in a patient with lymphoma.

PMID- 11978944
TI  - A comparative approach towards the understanding of adult neurogenesis.
AB  - In all vertebrate species examined thus far the production of new neurons in the
      central nervous system takes place not only during embryogenesis but also in
      adult life. However, although in mammals this so-called adult neurogenesis
      appears to be limited to a very few brain regions, in non-mammalian vertebrates
      new neurons are generated continuously in many regions of the adult central
      nervous system. This difference makes it particularly interesting to examine
      adult neurogenesis from a comparative point of view. Such an approach is likely
      not only to yield new insights into the evolution and function(s) of this
      phenomenon, but also to facilitate identification of central sites that, although
      quiescent in vivo, have retained their intrinsic potential to produce new cells
      during adulthood in mammals.

PMID- 11978945
TI  - Adult neurogenesis and neuronal regeneration in the central nervous system of
      teleost fish.
AB  - In contrast to mammals, teleost fish exhibit an enormous potential to produce new
      neurons in the adult central nervous system and to replace damaged neurons by
      newly generated ones. In the gymnotiform fish Apteronotus leptorhynchus, on
      average, 100,000 cells, corresponding to roughly 0.2% of the total population of
      cells in the adult brain, are in S-phase within any 2-h period. As in all other
      teleosts examined thus far, many of these cells are produced in specific
      proliferation zones located at or near the surface of ventricular,
      paraventricular, and cisternal systems, or in areas that are likely derived from
      proliferation zones located at ventricular surfaces during embryonic development.
      The majority of cells born in such proliferation zones migrate within the first
      few weeks following their generation to specific target areas. In the cerebellum,
      where approximately 75% of all brain cells are born during adulthood, cells
      originate from the molecular layers of the corpus cerebelli and the valvula
      cerebelli partes lateralis and medialis, as well as from the eminentia granularis
      pars medialis. From these proliferation zones, the young cells migrate to the
      associated granule cell layers or to the eminentia granularis pars posterior,
      respectively. In the course of their migration, the young cells appear to be
      guided by radial glial fibers. Upon arrival at their target region, approximately
      50% of the young cerebellar cells undergo apoptosis. The remaining cells survive
      for the rest of the fish's life, thus contributing to permanent brain growth. At
      least some cells differentiate into granule cell neurons. The potential to
      produce new neurons, together with the ability to guide the young cells to their
      target areas by radial glial fibers and to eliminate damaged cells through
      apoptosis, also forms the basis for the enormous regenerative capability of the
      central nervous system of Apteronotus, as demonstrated in the cerebellum and
      spinal cord. A factor involved in the cerebellar regeneration appears to be
      somatostatin, as the expression of this neuropeptide is up-regulated in a
      specific spatio-temporal fashion following mechanical lesions. Besides its
      involvement in neuronal regeneration adult neurogenesis in Apteronotus, and
      possibly teleost fish in general, appears to play a role in providing central
      neurons to match the growing number of sensory and motor elements in the
      periphery, and to establish the neural substrate to accommodate behavioral
      plasticity.

PMID- 11978947
TI  - Stem cells in the vertebrate retina.
AB  - The capacity for retinal regeneration in cold-blooded vertebrates has long been
      recognized. Regeneration occurs, in part, through a population of retinal stem
      cells residing at the peripheral margin of the retina. It has generally been
      thought that homeothermic vertebrates, such as birds and mammals, lack this so
      called ciliary marginal zone. Recent studies have, however, provided evidence
      that birds too possess a zone of cells at the retinal margin analogous to the
      ciliary marginal zone of fish and amphibians. In addition, there is an indication
      that, under certain conditions, Muller glia of the chicken retina can
      transdifferentiate into retinal progenitor/stem cells. These progenitor/stem
      cells then generate certain types of retinal neurons. Taken together, these
      studies have revealed an unexpected capacity for retinal regeneration in birds.

PMID- 11978946
TI  - Neurogenesis and neuronal regeneration in the adult reptilian brain.
AB  - Evidence accumulated over the last few decades demonstrates that all reptiles
      examined thus far continue to add neurons at a high rate and in many regions of
      the adult brain. This so-called adult neurogenesis has been described in the
      olfactory bulbs, rostral forebrain, all cortical areas, anterior dorsal
      ventricular ridge, septum, striatum, nucleus sphericus, and cerebellum. The rate
      of neuronal production varies greatly among these brain areas. Moreover, striking
      differences in the rate and distribution of adult neurogenesis have been noted
      among species. In addition to producing new neurons in the adult brain, lizards,
      and possibly other reptiles as well, are capable of regenerating large portions
      of their telencephalon damaged as a result of experimentally-induced injuries,
      thus exhibiting an enormous potential for neuronal regeneration. Adult
      neurogenesis and neuronal regeneration take advantage of the same mechanisms that
      are present during embryonic neurogenesis. New neurons are born in the ependyma
      lining the ventricles and migrate radially through the brain parenchyma along
      processes of radial glial cells. Several lines of evidence suggest that radial
      glial cells also act as stem cells for adult neurogenesis. Once they reach their
      final destination, the young neurons extend axons that reach appropriate target
      areas. Tangential migration of neurons alongside the ventricular ependyma has
      also been reported. Most of these tangentially migrating neurons seem to be
      destined for the olfactory bulbs and are, thus, part of a system similar to the
      mammalian rostral migratory stream. The proliferation and recruitment of new
      neurons appear to result in continuous growth of most areas showing adult
      neurogenesis. The functional consequences of this continuous generation and
      integration of new neurons into existing circuits is largely conjectural, but
      involvement of these phenomena in learning and memory is one likely possibility.

PMID- 11978948
TI  - Challenges for brain repair: insights from adult neurogenesis in birds and
      mammals.
AB  - Adult neurogenesis is a widespread phenomenon occurring in many species,
      including humans. The functional and therapeutic implications of this form of
      brain plasticity are now beginning to be realized. Comparative approaches to
      adult neurogenesis will yield important clues about brain repair. Here, we
      compare adult neurogenesis in birds and mammals. We review recent studies on the
      glial identity of stem cells that generate new neurons, the different modes of
      migration used by the newly generated neurons to reach their destinations, and
      how these systems respond to experimentally induced cell death. We integrate
      these findings to address how comparative analysis at the molecular level might
      be used for brain repair.

PMID- 11978949
TI  - Pericarditis due to anaerobic bacteria.
AB  - This review describes the microbiology, diagnosis and management of pericarditis
      due to anaerobic bacteria. The predominant anaerobes recovered from patients with
      pericarditis were: gram-negative bacilli (mostly of the Bacteroides fragilis
      group), anaerobic streptococci, Clostridium spp., Fusobacterium spp., and
      Bifidobacterium spp. Anaerobic bacteria can be isolated in pericarditis resulting
      from the following mechanisms: (1) spread from a contiguous focus of infection,
      either de novo or after surgery or trauma (pleuropulmonary, esophageal fistula or
      perforation, and odontogenic); (2) spread from a focus of infection within the
      heart, most commonly from endocarditis; (3) hematogenous infection, and (4)
      direct inoculation as a result of a penetrating injury or cardiothoracic surgery.
      No differences were found in the clinical diagnostic features between cases of
      pericarditis due to anaerobic bacteria and those due to aerobic and facultative
      bacteria. Anaerobic gram-negative bacilli have increased their resistance to
      penicillins and other antimicrobials in the last decade. Complete identification
      and testing for antimicrobial susceptibility and lactamase production are
      therefore essential for the management of infections caused by these bacteria.
      Treatment of pericarditis involving anaerobic bacteria includes the use of
      antibiotic therapy effective against these organisms.

PMID- 11978951
TI  - The 27-bp tandem repeat polymorphism in intron 4 of the endothelial nitric oxide
      synthase gene is not associated with coronary artery disease in a hospital-based
      Taiwanese population.
AB  - We studied whether the 27 base pair (bp) tandem repeat polymorphism in intron 4
      of the endothelial nitric oxide synthase (eNOS) gene was associated with coronary
      artery disease (CAD) in a hospital-based Taiwanese population. We included 219
      consecutive patients who underwent coronary angiography at our institution. Two
      alleles, containing 4 (eNOS4a) and 5 repeats (eNOS4b), were identified after
      polymerase chain reaction amplifying intron 4 of the eNOS gene. The genotype
      frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 77.9, 21.5 and 0.6% in CAD
      subjects, and 80, 20 and 0% in control subjects (Fisher's exact test, p = 0.90),
      respectively. The odds ratio (OR) for CAD in patients with at least one eNOSa
      allele was 1.2 (0.5-2.9) after adjustment for classical CAD risk factors. The
      eNOS4a allele was not associated with the severity of CAD (Fisher's exact test, p
      = 0.90) and the occurrence of acute myocardial infarction (AMI) or unstable
      angina (adjusted OR 0.6, 0.3-1.6) in patients with CAD. In conclusion, the 27-bp
      repeat polymorphism of the eNOS gene was not associated with CAD and the
      occurrence of AMI or unstable angina in a hospital-based Taiwanese population.

PMID- 11978950
TI  - New advances in lipid-modifying therapies for reducing cardiovascular risk.
AB  - Over the last 30 years, several epidemiological and prospective studies have
      identified a number of risk factors for the development of cardiovascular
      disease. Lipid abnormalities are central among these risk factors, and their
      correction has been a major target for the medical community. The 3-hydroxy-3
      methyl glutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors (statins) are
      the most widely prescribed and best tolerated of the currently available lipid
      modifying therapies. Newer agents in this class (e.g. rosuvastatin) have been
      developed that have proven to be more effective at lowering levels of low-density
      lipoprotein cholesterol (LDL-C). New formulations of drugs such as nicotinic acid
      can improve treatment regimens and reduce unpleasant side-effects, thereby
      improving patient compliance with this therapy. In terms of developing novel
      drugs, the introduction of cholesterol absorption inhibitors (e.g. ezetimibe) and
      ACAT inhibitors (e.g. avasimibe) will provide clinicians with therapies that
      exploit different therapeutic pathways to those currently being utilised.
      Combining these agents with statins could produce greater improvements in lipid
      profile than those seen to date. In addition, advances in our understanding of
      the pathophysiology of dyslipidaemia have led to the identification of other
      novel therapeutic targets, including cholesteryl ester transfer protein. Studies
      with experimental drugs have already demonstrated the potential of these
      approaches.

PMID- 11978952
TI  - Left ventricular hypertrophy and diastolic dysfunction in healthy pregnant women.
AB  - OBJECTIVE: The purpose of this study was to examine which hemodynamic parameters
      change under the natural volume overload of pregnancy. STUDY DESIGN: 46 healthy
      pregnant women were echocardiographically examined during the course of
      pregnancy. To evaluate left ventricular diastolic function, mitral inflow and
      pulmonary venous flow profiles were used. Fractional shortening and left
      ventricular muscle mass were calculated. RESULTS: In the course of pregnancy the
      left ventricular muscle mass index increased (from 66 +/- 6 to 96 +/- 9 g/m(2)),
      fractional shortening decreased (from 38 +/- 4 to 32 +/- 6%) and a disturbed
      diastolic relaxation pattern was documented. Eight weeks after delivery, all left
      ventricular systolic and diastolic functional parameters returned to normal
      values. CONCLUSION: The natural volume overload in pregnancy leads to a
      reversible 'physiological' left ventricular hypertrophy, a short-term decrease in
      systolic function and a significant change in left ventricular diastolic
      function.

PMID- 11978953
TI  - Sildenafil in the cardiologist's office: patients' attitudes and physicians'
      practices toward discussions about sexual functioning.
AB  - Sildenafil is a medication increasingly prescribed to improve sexual function in
      patients who have erectile dysfunction. Because a major contraindication to the
      use of sildenafil is a history of coronary disease and the concomitant use of
      nitrates, it becomes increasingly important for cardiologists to prescribe this
      medication. We evaluated the nature of discussions in all 70 patients for whom
      sildenafil was prescribed in a cardiology practice between April and July 1998.
      We used a standardized questionnaire to determine the patients' perspective on
      the sexual history and the extent to which they wanted their physicians to take a
      detailed history about sexuality. A separate chart review evaluated the nature of
      physicians' discussions about sexual functioning before sildenafil was
      prescribed. Fifty-five of the 70 patients (79%) responded to the survey. The
      majority of patients (98%) felt that physicians should talk with patients about
      sexual functioning. However, only 73% of patients believed their doctor was
      comfortable talking with them about this subject. Sixty percent of patients
      reported that their doctor had ever talked with them about erectile function and
      only 15% had ever had a discussion with their doctors about specific difficulties
      during intercourse. Based on the results of the chart review, only 24% of the
      patients ever specifically discussed the used of sildenafil with their physician
      prior to the time that it was prescribed. The results of the study suggest that
      patients with coronary disease erectile dysfunction are comfortable talking with
      their physicians about sexual functioning, but these conversations occur
      infrequently.

PMID- 11978954
TI  - Mycoplasma-associated carditis. Case reports and review.
AB  - We present 2 cases and examine the developments that occurred in diagnosis,
      treatment, and outcome of 19 additional patients with mycoplasmal peri- and
      myocarditis. The mean age of this group was 33 years. The final diagnoses were
      pericarditis (n = 15), myocarditis (n = 5), and myopericarditis (n = 1);
      pulmonary involvement was noted in 13 patients. Serology established the
      diagnosis in 12 cases, and isolation in 9 others. In contrast to previous
      reviews, an echocardiogram was carried out in all patients, thus enabling
      pericardiocentesis in 13 patients. Antibiotics were given to 19 patients,
      including 4 who received a newer macrolide. Three patients were left with long
      term sequelae, and 1 patient died. The outcome of Mycoplasma carditis has
      improved over the years, although a minority of patients may suffer long-term
      sequelae.

PMID- 11978955
TI  - Long-term results of elective stenting for severe carotid artery stenosis in
      Taiwan.
AB  - Stenting for severe carotid stenosis has been proposed as an alternative for
      patients with high surgical risk for endarterectomy, but its effectiveness and
      safety has never been evaluated in large case series in a pure Asian population.
      One hundred and eighteen ethnic Chinese patients (mean age 72.8 years) with 129
      severely narrowed carotid arteries were stented electively using self-expanding
      stents. The mean pre-treatment diameter stenosis was 85% and final residual
      diameter stenosis 14%. The peri-procedural stroke and death rate was 4.2%. One
      (0.8%) late ischemic stroke and 2 (1.7%) deaths occurred during a mean follow-up
      of 16.3 months, and the restenosis rate was 3.1%. Carotid stenting, therefore,
      can be done safely and effectively in Chinese patients.

PMID- 11978956
TI  - Metoprolol treatment to prevent restenosis following percutaneous transluminal
      coronary angioplasty.
AB  - This study tested the hypothesis that metoprolol reduces the restenosis rate
      after percutaneous transluminal coronary angioplasty (PTCA) in native coronary
      arteries as compared to placebo. Apart from prognostic clinical effects in the
      treatment of patients with coronary heart disease, several in vivo and ex vivo
      studies have demonstrated antiproliferative and antiatherogenic effects of beta
      blockers. In the present study, 192 male patients were randomized in a double
      blind fashion to metoprolol sustained-release treatment or placebo starting at
      least 1 day before angioplasty. Lesion diameters and restenosis rates were
      evaluated using automatic edge detection systems. The study endpoint was the
      angiographic restenosis rate 4 months after PTCA. Ninety-seven randomized
      patients had a control angiography a mean of 4.5 months after PTCA. Dropouts were
      evenly distributed between the metoprolol and placebo groups. Lumen loss in the
      target lesion was 0.36 mm in the metoprolol group and 0.32 mm in the placebo
      group. Restenosis rates averaged 57.5% in the metoprolol group and 44.2% in the
      placebo group using conventional restenosis criteria. Taking metoprolol serum
      levels above 50 mmol/l as an indication of definite compliance with the
      metoprolol treatment, the restenosis rate was 58.3%. In conclusion, 95 mg of
      sustained-release metoprolol failed to reduce the restenosis rate following
      angioplasty in native coronary arteries.

PMID- 11978958
TI  - Is the site of thrombus formation in the left atrial appendage associated with
      the risk of cerebral embolism?
AB  - Atrial fibrillation (AF) is a risk factor for cerebral embolism, with the left
      atrial appendage (LAA) being considered as the source of emboli. However, the
      relationship between the histologic properties of LAA thrombi and the occurrence
      of cerebral embolism is not known. Seventy-six hearts from patients who died
      within 1 month after cerebral embolism were studied at autopsy. Patients were
      grouped according to the presence of AF and the presence of valvular disease
      (VD). We determined whether the LAA thrombi adhered to the trabecular region or
      the remainder of the LAA. LAA thrombi were grouped into three stages: a fresh
      stage in which thrombi consisted of fibrin and platelets, an organizing stage in
      which angiogenesis was observed in the thrombi, and an organized stage in which
      endothelial cells covered the surface of the thrombi. The AF+/VD- group included
      19 patients (25.0%), the AF+/VD+ group 8 (10.5%), the AF-/ VD- group 37 (48.7%),
      and the AF-/VD+ group included 12 patients (15.8%). LAA thrombi were observed in
      15 patients (78.9%) in the AF+/VD- group, and all of the thrombi adhered to the
      trabecular region. Thrombi in the fresh and the organizing stages were observed
      in 10 patients (66.7%). Patients in the AF+/VD- group accounted for about 25% of
      the cases of cerebral embolism. All of these thrombi were attached to the
      trabecular region, and about 70% of them could represent an embolic source.

PMID- 11978957
TI  - Lung uptake of technetium-99m tetrofosmin in healthy subjects is related to
      smoking habits.
AB  - To determine the influence of smoking on lung uptake of technetium-99m
      tetrofosmin (Tc-TF) during myocardial perfusion imaging, we examined 50 healthy
      subjects with normal myocardial perfusion single photon emission computed
      tomography findings, normal coronary angiograms, and no evidence of left
      ventricular hypertrophy. The 50 healthy subjects were divided into two groups.
      Group 1: 25 healthy subjects had smoking histories of at least 10 pack-years.
      Group 2: 25 healthy subjects were nonsmokers. Lung to heart ratios (L/H ratios)
      calculated from anterior planar images during exercise and rest states of Tc-TF
      myocardial perfusion imaging were obtained for all of the 50 healthy subjects.
      L/H ratios calculated from Tc-TF myocardial perfusion imaging in smokers were
      significantly higher than in nonsmokers during both exercise and rest states.
      However, no significant difference in L/H ratios was found between exercise and
      rest states in smokers and nonsmokers. In addition, a positive but nonsignificant
      correlation was found between smoking pack-years and either rest or exercise L/H
      ratios. When L/H ratios are used as a clinical diagnostic tool in Tc-TF
      myocardial perfusion imaging, we must consider that L/H ratios in smokers are
      higher than in nonsmokers.

PMID- 11978959
TI  - Chronic beneficial effects of type 1 angiotensin II receptor antagonist in
      patients with chronic hypoxemic pulmonary diseases.

PMID- 11978960
TI  - Paralytic ileus induced by the combined use of nifedipine and diltiazem in the
      treatment of vasospastic angina.

PMID- 11978962
TI  - Genetic abnormalities in a pre and post-chemotherapy hepatoblastoma.
AB  - Comparative genomic hybridization (CGH) analysis was performed on both a pre- and
      post-chemotherapy hepatoblastoma from a 24-month-old female patient. The
      diagnostic sample obtained from a tru-cut biopsy was a mixed epithelial
      mesenchymal tumor with both fetal and embryonal patterns present. In contrast,
      the post-chemotherapy tumor exhibited a prominent anaplastic large cell
      population focally reminiscent of pleomorphic hepatocellular carcinoma (HCC). CGH
      analysis indicated that there were similarities as well as differences in the
      gains and losses of genetic material in each tumor. The diagnostic sample had
      gains of chromosome 1q, 2, 2(q31q33), 7, 8q, 12(q15q22), 17q and 20 material,
      while the post-chemotherapy tumor had gains of 1q, 2, 7, 8q, 10, 17q and 20
      material. In addition, the pre- and post-chemotherapy samples may have incurred
      loss of chromosome 17p material. The main differences between the two samples
      involved localized gain of 2(q31q33) and 12(q15q22) in the pre-chemotherapy
      sample, and gain of chromosome 10 material in the post-chemotherapy tumor. The
      patient subsequently developed metastatic nodules in her lungs, the histology of
      which was identical in pattern to the diagnostic pattern, and appeared to have
      localized gain of 2(q31q33) and 12(q15q22). These results are consistent with
      published results that gain of chromosome 8q and 20 are associated with an
      unfavorable prognosis.

PMID- 11978961
TI  - Report on the Eleventh International Workshop on the Identification of
      Transcribed Sequences 2001. November 9-11, 2001. Washington, DC, USA.

PMID- 11978963
TI  - Detection of microdeletions in the short arm of the X chromosome by chromosome
      stretching.
AB  - The present study was focused on the resolution of "chromosome stretching". In
      order to determine if this method can be used for the detection of
      microdeletions, the p-arms of 13 normal X chromosomes were stretched as well as
      of those with three different deletions of known size within the DMD/BMD region
      in Xp21 (case A: 0.42-0.45 Mb, case B: 2.3-2.9 Mb and case C: 3.0-3.5 Mb). The
      process of band splitting was recorded on a video-tape and the resulting banding
      pattern analyzed. Stretching of the normal Xp-arms led to a splitting on a
      maximum band level of 1400 and showed in all cases an identical banding pattern
      with 13 Giemsa-dark subbands. All new Giemsa-dark and -light subbands were
      derived from the three initial Giemsa-dark bands at the 400 band level according
      to ISCN (1995): five subbands from Xp21, four subbands from Xp11.3 and Xp22.2,
      respectively. The origin of these subbands is partly in contrast to the high
      resolution ISCN (1995) ideograms: subband Xp11.22 does not originate from the
      Giemsa-light band Xp11.2, but from the Giemsa-dark band Xp11.3; Xp22.12
      originates from Xp21; Xp22.32 from Xp22.2. Stretching of the chromosomes
      containing deletions showed in cases A and B no differences in banding patterns
      and splitting order compared to normal X chromosomes. Only in patient C was a
      significant difference with the normal pattern visible due to the absence of one
      dark subband. In this case only four Giemsa-dark subbands derived from band Xp21.
      Thus, at least in the DMD/BMD region, the minimal size of a deletion detected by
      chromosome-stretching-generated high-resolution ideograms is about 3.0-3.5 Mb.

PMID- 11978964
TI  - Intragenic breakpoint within RAD51L1 in a t(6;14)(p21.3;q24) of a pulmonary
      chondroid hamartoma.
AB  - Rearrangements involving chromosome region 14q23-->q24 represent a main
      cytogenetic subgroup in a variety of benign solid tumors. Recently, in uterine
      leiomyomas containing the classical t(12;14)(q15;q23-->q24), the primary
      chromosome 14 target gene was identified as the protein kinase-encoding gene
      RAD51L1. In this report we show that RAD51L1 is also involved in the frequently
      occurring t(6;14) (p21;q23-->q24) in pulmonary chondroid hamartomas.

PMID- 11978965
TI  - Characterization of two novel genes, WBSCR20 and WBSCR22, deleted in Williams
      Beuren syndrome.
AB  - Williams-Beuren syndrome (WBS), due to a contiguous gene deletion of
      approximately 1.5 Mb at 7q11.23, is a complex developmental disorder with
      multisystemic manifestations including supravalvular aortic stenosis (SVAS) and a
      specific cognitive phenotype. Large repeats containing genes and pseudogenes
      flank the deletion breakpoints, and the mutation mechanism commonly appears to be
      unequal meiotic crossover. Except for elastin, hemizygosity of which is
      associated with supravalvular aortic stenosis, it is unknown which of the 18
      genes in the deletion area contributes to the phenotype. Here, we report the
      identification and characterization of two novel genes, WBSCR20 and WBSCR22,
      which map to the common WBS deletion region. WBSCR22 encodes a putative
      methyltransferase protein strongly expressed in heart, skeletal muscle and
      kidney. WBSCR20 encodes a novel protein expressed in skeletal muscle with
      similarity to p120 (NOL1), a 120-kDa proliferation-associated nucleolar antigen,
      a member of an evolutionarily conserved protein family. A highly similar putative
      gene, WBSCR20B, flanks the WBS deletion at the telomeric side. Hemizygous
      deletion of either of the novel genes might contribute to the growth retardation,
      the myopathy or the premature aging effects in the pathogenesis of WBS.

PMID- 11978966
TI  - Primed in situ labeling: sensitivity and specificity for detection of alpha
      satellite DNA in the centromere regions of chromosomes 13 and 21.
AB  - The centromeric alpha-satellite DNA subfamilies from chromosomes 13 and 21 are
      almost identical in sequence. So far it has proven difficult to discriminate
      between sequence variations in the chromosome 13 and 21 alpha-satellite regions
      using in situ techniques. To analyze whether the method of modified single-color
      and double-color PRINS could be used to detect single nucleotide polymorphisms
      within this region, we used previously published primers D13Z and D21Z that
      differ in the terminal 3'-nucleotide and an additionally constructed primer
      "D13/21-test" lacking the final nucleotide at the 3' end. The results show that a
      one-base pair mismatch at the 3' end is sufficient to be detected by PRINS.
      Surprisingly, only about 35% of our samples exhibited the expected combination of
      two chromosomes 13 specifically labeled with only primer D13Z and two chromosomes
      21 specifically labeled with only primer D21Z. The rest of the samples showed a
      polymorphic distribution of the target sequence for the primers, therefore these
      primers are not suited for routine detection of chromosomes 13 and 21 during
      interphase. Our data indicate that an interchromosomal exchange of alpha
      satellite DNA takes place between chromosomes 13 and 21, possibly due to a
      concerted evolution process.

PMID- 11978968
TI  - Molecular cloning, structure and expression of a novel nuclear RNA-binding
      cyclophilin-like gene (PPIL4) from human fetal brain.
AB  - The cyclophilins are members of a highly conserved, ubiquitous family, and play
      an important role in protein folding, immunosuppression by cyclosporin A (CsA),
      and infection of HIV-1 virions. Here we report that a novel member of the
      cyclophilin family, PPIL4, was cloned and identified during the large-scale
      sequencing analysis from a human fetal brain cDNA library. The PPIL4 gene encodes
      a protein which shares 96% amino acid identity with a protein encoded by a
      putative gene recently cloned from several different early stages of mouse
      embryo, and its homologues are found in several other organisms. According to
      bioinformatics analysis, the PPIL4 gene was found to be located in chromosome
      6q24-->q25. Besides the PPIase motif, PPIL4 also has an RNA recognition motif
      (RRM), a pair of bipartite nuclear targeting sequences, and a lysine rich domain.
      RT-PCR analysis indicated that PPIL4 gene expression is abundant in kidney but
      has a ubiquitously low expression pattern in other human adult tissues.

PMID- 11978967
TI  - Human ribonucleotide reductase M2 subunit gene amplification and transcriptional
      regulation in a homogeneous staining chromosome region responsible for the
      mechanism of drug resistance.
AB  - In our previous publication it was shown that a Gemcitabine-resistant KBGem clone
      derived from step-wise exposure to Gemcitabine resulted in overexpression of the
      human Ribonucleotide Reductase M2 subunit (hRRM2) mRNA and protein (Goan et al.,
      1999). In this study we confirm these results and show that the hRRM2 gene
      amplification arises in a homogeneous staining region (hsr) derived from
      chromosome translocation. The hydroxyurea-resistant clone (KBHURs) was studied as
      a comparison. PCR analysis of the hRRM2 gene promoter confirmed the
      amplification. Northern and Western blots were further employed to confirm the
      gene amplification and hRRM2 mRNA and protein expression were compatible with the
      level of drug resistance. Cells synchronized by serum starvation and then
      returned to serum-containing growth conditions showed a rapid induction of high
      levels of transcription of the hRRM2 gene. To clarify whether expression of hRRM2
      mRNA was regulated at a transcriptional level, several transcription factors,
      including AP-1, Sp1, AP-2, CREB, NF-kappa B, and OCT1, were examined by gel-shift
      assay. Interestingly, the KBGem clone was regulated by different transcription
      factors than the KBHURs clone. Compared to the wild-type KB cells (KBwt), the
      KBGem clone exhibited a different binding pattern for Sp1 and NF-kappa B. The
      KBHURs clone, however, demonstrated a unique binding pattern with AP-1 and CREB,
      different from the KBwt control as well as the KBGem clone. Therefore, we
      conclude that the drug-resistant phenotype is associated with human RRM2 gene
      amplification from a homogeneous staining chromosome region and altered
      transcription regulation. Each clone demonstrated a unique pattern of
      transcription factor binding that may play a vital role in the mechanism of drug
      resistance.

PMID- 11978969
TI  - Molecular cloning and characterization of a novel human gene (HSPBAP1) from human
      fetal brain.
AB  - Rat PASS1 is a novel protein binding specifically to hsp27 and thus plays a role
      in regulating stress response in the living cell. Here we report on a human
      homologue of PASS1, encoded by the gene HSPBAP1. The gene was cloned and
      identified during a large-scale sequencing analysis of a human fetal brain cDNA
      library. The human protein shared 80% amino acid identity with rat PASS1.
      According to bioinformatics analysis, the HSPBAP1 gene is located on chromosome
      3q21. RT-PCR analysis indicated that HSPBAP1 was abundant in thymus and pancreas
      but had a ubiquitously low expression pattern in other human adult tissues except
      for brain where it was absent.

PMID- 11978970
TI  - Characterization of the human ribonucleotide reductase M2 subunit gene; genomic
      structure and promoter analyses.
AB  - Ribonucleotide Reductase (RR) is a rate-limiting enzyme in DNA synthesis and
      repair consisting of two subunits, M1 and M2. RRM2 plays a role in cell
      proliferation, tumorgenicity, metastasis and drug resistance. To better
      understand the regulation of RRM2, we have sequenced the entire human RRM2 gene.
      Approximately 10.3 kb of genomic DNA was sequenced and deposited to GenBank
      (accession number AY032750). Intron/exon junctions were identified and the gene
      was found to consist of ten exons. Two transcription initiation sites were
      identified and correspond to mRNA transcripts of 3.4 kb and 1.65 kb. Deletion
      analysis of the 5'-flanking region showed that there was promoter activity
      consistent with the presence of two separate promoters driving expression of the
      two RRM2 transcripts. A thorough analysis of the genomic sequence and promoter
      regions of the RRM2 gene will provide insight into the processes involved in
      tumor transformation and drug resistance.

PMID- 11978972
TI  - Non-random chromosomal distribution of SSLPs: systematic assessment using a novel
      genetic linkage map between two closely related rat strains.
AB  - Simple sequence length polymorphisms (SSLPs) are a widely used tool for genetic
      studies in humans and model animals. Experimental crosses among closely related
      strains that differ primarily in the trait that is to be mapped carry the
      advantage of avoiding co-segregation of potentially confounding traits. However,
      their realization is encumbered by the limited availability of newly arisen
      informative SSLPs among such strains. Here we report the establishment of a
      genome-wide SSLP panel for the spontaneously hypertensive rat (SHR) and its close
      relative, the stroke-prone SHR (SHRSP), consisting of a total of 273 polymorphic
      markers that were found among 2,734 rat SSLPs screened. In addition to
      limitations in numbers, we also found the distribution of informative markers to
      be heterogeneous, with clustering and paucity of informative markers,
      respectively, in particular regions. Notably, the majority of regions thus
      identified was also seen when we examined an unrelated set of strains from the
      literature, indicating, on a more generic level, the presence of mutagenically
      more and less stable genomic regions.

PMID- 11978971
TI  - cDNA cloning, genomic organization and expression of the novel human
      metallophosphoesterase gene MPPE1 on chromosome 18p11.2.
AB  - We have isolated a 1,926-bp cDNA that encodes a novel polypeptide of 396 amino
      acid residues with a calculated molecular mass of 45.2 kDa. This MPPE1
      polypeptide consists of a predicted signal sequence of 45 residues at the N
      terminus, a 240-amino acid metallo-phosphoesterase domain, and a 24-amino acid
      transmembrane domain at the C-terminus. The genomic organization of the human
      MPPE1 gene proved to consist of 14 exons and to span about 27 kb. The gene was
      located on chromosome 18p11.2, adjacent to the G protein Golf alpha gene (GNAL),
      in tail-to-tail orientation, partially overlapping with the 3' UTR of the latter
      gene. MPPE1 is expressed as an mRNA of 2.2 kb in the brain, but not in any other
      tissues studied here. 3' RACE analysis defined a single functional
      polyadenylation site within the 3' UTR of the GNAL gene, while RT-PCR analysis
      revealed an alternatively spliced form of MPPE1, which included an additional
      exon located within the last intron. The alternatively spliced form encoded a
      truncated variant of MPPE1 with a calculated molecular mass of 38.8 kDa that
      lacks the C-terminal transmembrane domain.

PMID- 11978973
TI  - XX:XY sex chromosome system with X heterochromatinization: an early stage of sex
      chromosome differentiation in the Neotropic electric eel Eigenmannia virescens.
AB  - An early stage of sex chromosome differentiation is reported to occur in the
      electric eel Eigenmannia virescens (Pisces, Sternopygidae) from populations of
      two tributaries of the Parana river system (Brazil). Cytogenetic studies carried
      out in the two populations showed that the Mogi-Guacu population is characterized
      by 2n = 38 chromosomes and undifferentiated sex chromosomes and the Tiete
      population presents 2n = 38 both for males and females and an XX:XY sex
      chromosome system. The X-chromosome is acrocentric, easily recognized by the
      presence of a conspicuous heterochromatin block in its distal portion; the Y
      chromosome is probably one of the medium sized acrocentrics present in the male
      karyotype. BrdU induced R-bands of the two populations did not reveal any
      difference in the euchromatic regions of the chromosomes. AluI and HaeIII
      restriction enzyme digestion patterns and chromomycin A3 staining of the X
      chromosome are presented. The possible role of heterochromatinization in the
      evolution of sex chromosomes in fish is discussed.

PMID- 11978974
TI  - The assignment of PRKCI to bovine chromosome 1q34-->q36 by FISH suggests a new
      assignment to human chromosome 3.
AB  - Two bovine BAC clones were identified by PCR as containing the bovine gene PRKCI.
      Both clones were assigned by FISH to bands q34-->q36 on BTA1. The sequence
      information derived from genomic DNA and from both clones was identical and
      showed a high degree of homology to human PRKCI (HSAXq21.3, 95.5% homology), and
      mouse Prkcl (MMU3, 13.8 cM, 87.6% homology) and rat Prkcl (88.8% homology). This
      assignment could suggest a disruption of the synteny conservation of mammalian X
      linked genes, but most likely suggests a misassignment of this gene to the human
      X.

PMID- 11978975
TI  - Genetic and physical mapping, expression analysis and partial sequence of porcine
      PER1.
AB  - The porcine PER1 gene was mapped to chromosome 12q1.4-->q1.5 using fluorescence
      in situ hybridisation. A polymorphic microsatellite marker (S0601) was isolated
      from a BAC clone shown to contain the PER1 gene. Linkage analysis assigned S0601
      distal to ALOX12 on SSC12, providing further evidence for the conservation of
      synteny between HSA17 and SSC12. RT-PCR analysis demonstrated the expression of
      PER1 in all 11 tissues tested, consistent with the data from other mammalian
      species. Part of the PER1 gene was sequenced, homologous to exons 2-14 of the
      human gene and encoding the N-terminus of porcine PER1. The predicted amino acid
      sequence of the partial pig PER1 protein shares over 96% identity with its human
      orthologue.

PMID- 11978976
TI  - Cytogenetics of collared lemmings (Dicrostonyx groenlandicus). II. Meiotic
      behavior of B chromosomes suggests a Y-chromosome origin of supernumerary
      chromosomes.
AB  - The patterns of synapsis and chiasma formation of the B chromosomes of male
      collared lemmings (Dicrostonyx groenlandicus) were analyzed by light and electron
      microscopy and compared to expectations for various hypotheses for the
      intragenomic origin of supernumerary chromosomes. Pachytene analysis revealed a
      variety of synaptic configurations including B-chromosome univalents, bivalents
      and trivalents. In approximately one-half of the pachytene nuclei examined, B
      chromosomes were in synaptic associations with the normally unpaired portion of
      the Y chromosome. The B-chromosome configurations at pachynema, including those
      involving the Y chromosome, were maintained into diakinesis and metaphase I. The
      meiotic behavior of the B chromosomes was inconsistent with their derivation from
      centric-fusion products, isochromosome formation, small-autosome polysomy, or the
      X chromosome. However, the frequent synapsis and apparent recombination between B
      chromosomes and the Y chromosome implicate this sex chromosome as a possible
      source of the B chromosomes in collared lemmings.

PMID- 11978977
TI  - Characterization and comparative mapping of the porcine CTSL gene indicates a
      novel synteny between HSA9q21-->q22 and SSC10q11-->q12.
AB  - Cathepsin L (CTSL) is a lysosomal cysteine protease with potent elastase and
      collagenase activities. Its high activity in the uterine lumen during the period
      of placental attachment has led to speculation that CTSL may play an important
      role during embryonic implantation in the pig. Cathepsins have also been
      implicated in blastocyst implantation in other species like cat, rat and man. We
      isolated a PAC clone containing the porcine CTSL gene and determined the complete
      DNA sequence of the gene, which spans about 5.6 kb and consists of eight exons.
      The CTSL transcript encodes a primary peptide of 334 amino acids sharing 73-78%
      identity with other mammalian cathepsin L precursor proteins. Based on
      fluorescence in situ hybridization and radiation hybrid mapping, the porcine CTSL
      gene was assigned to chromosome 10q11--> q12.

PMID- 11978978
TI  - Chromosome map of cosmid clones constructed with Chinese hamster genomic DNA.
AB  - By fluorescence in situ hybridization (FISH), we constructed a chromosome map of
      324 site-specific clones and 119 painting clones, which were isolated from a
      cosmid library of Chinese hamster genomic DNA. The site-specific clones were
      distributed among all chromosomes except chromosome 10 and the Y chromosome. On
      the other hand, FISH signals of painting clones were mainly found in
      heterochromatic regions. First, the various combinations of clones painting
      centromeric regions suggest that the centromeric heterochromatin of Chinese
      hamster chromosomes is extremely diverse in its repetitive sequence composition.
      Second, the long arm of the X chromosome and the whole Y chromosome, both
      heterochromatic regions, were simultaneously painted by many clones. The pattern
      of co-localization indicated that a proximal segment of the long arm of the X
      chromosome matches the complete long arm of the Y chromosome, whereas a distal
      segment of the long arm of the X chromosome is comparable to the whole short arm
      of the Y chromosome. Thus, these findings suggest that the corresponding segments
      of the X and Y-chromosomes have common repeated DNA elements.

PMID- 11978979
TI  - A comparative cytogenetic study of chromosome homology between chicken and
      Japanese quail.
AB  - In order to construct a chicken (Gallus gallus) cytogenetic map, we isolated 134
      genomic DNA clones as new cytogenetic markers from a chicken cosmid DNA library,
      and mapped these clones to chicken chromosomes by fluorescence in situ
      hybridization. Forty-five and 89 out of 134 clones were localized to
      macrochromosomes and microchromosomes, respectively. The 45 clones, which
      localized to chicken macrochromosomes (Chromosomes 1-8 and the Z chromosome) were
      used for comparative mapping of Japanese quail (Coturnix japonica). The
      chromosome locations of the DNA clones and their gene orders in Japanese quail
      were quite similar to those of chicken, while Japanese quail differed from
      chicken in chromosomes 1, 2, 4 and 8. We specified the breakpoints of pericentric
      inversions in chromosomes 1 and 2 by adding mapping data of 13 functional genes
      using chicken cDNA clones. The presence of a pericentric inversion was also
      confirmed in chromosome 8. We speculate that more than two rearrangements are
      contained in the centromeric region of chromosome 4. All 30 clones that mapped to
      chicken microchromosomes also localized to Japanese quail microchromosomes,
      suggesting that chromosome homology is highly conserved between chicken and
      Japanese quail and that few chromosome rearrangements occurred in the evolution
      of the two species.

PMID- 11978980
TI  - Assignment of the porcine inter-alpha trypsin inhibitor heavy chain 4 (ITIH4)
      gene to SSC13q2.1-->q2.2 by fluorescence in situ hybridization and radiation
      hybrid mapping.

PMID- 11978981
TI  - Assignment of two new loci for gamma 1 porcine endogenous retroviruses (gamma 1
      PERV) to pig chromosome bands 2q21 and 11q12 by in situ hybridization.

PMID- 11978982
TI  - Assignment of surfactant protein A (SFTPA) and surfactant protein D (SFTPD) to
      pig chromosome band 14q25-->q26 by in situ hybridization.

PMID- 11978984
TI  - Assignment of S100A11 and SELE to porcine chromosome 4 by in situ hybridization.

PMID- 11978983
TI  - Assignment of the homologue of human JAG1 to chicken chromosome 3q11 by in situ
      hybridization.

PMID- 11978985
TI  - Assignment of the mouse Park2 (PARKIN), the homologue to a new human Parkinson
      candidate gene, to the telomeric region of mouse 17A3.2-3.3, by in situ
      hybridization.

PMID- 11978986
TI  - Assignment of the feline Fas (TNFRSF6) gene to chromosome D2p13-->p12.2 by
      fluorescence in situ hybridization.

PMID- 11978987
TI  - Assignment of lactotransferrin (LTF) to porcine chromosome band 13q21 by in situ
      hybridization.

PMID- 11978988
TI  - Chromosome mapping and sequence variation of the murine Ras effector gene Nore1.

PMID- 11978989
TI  - Complications in surgery--let's face them.

PMID- 11978990
TI  - Management of Complications of Gastro-Intestinal Surgery. Proceedings of the
      ISDS/EDS Postgraduate Course at the 9th United European Gastroenterology Week.
      October 7, 2001. Amsterdam, The Netherlands.

PMID- 11978991
TI  - Disturbed anastomotic healing after esophagectomy: a novel treatment of a benign
      tracheo-neo-esophageal fistula.
AB  - In this report a 65-year-old man is presented who developed a benign tracheo-neo
      esophageal fistula 1 month after esophageal resection due to confined leakage of
      the cervical anastomosis. After unsuccessful conservative treatment, the fistula
      was partly excised via a cervical approach and a T-drain was inserted in the
      esophagus, thus creating a new fistula to the skin. Over a period of 8 weeks, the
      long mediastinal fistula track obliterated, and after removal of the T-drain the
      (neo-)esophagocutaneous fistula closed rapidly.

PMID- 11978992
TI  - Anastomotic complications after esophagectomy.
AB  - Anastomotic complications after esophagectomy continue to be a burden
      jeopardizing the quality of life and of swallowing. However, incidence, mortality
      and morbidity of anastomotic complications have substantially decreased in recent
      years. It seems that this is not so much related to the use of a particular
      conduit, approach or route for reconstruction, but rather related to refinement
      in anastomotic techniques and perhaps even more to progress in modern
      perioperative management. Knowledge of surgical anatomy and meticulous technique
      are of paramount importance and obviously related to individual expertise. As to
      the management, most leaks can be treated by conservative measures and
      reintervention surgery today is rather exceptional. Early endoscopy and
      dilatation seem to decrease the incidence and severity of anastomotic stenosis.

PMID- 11978993
TI  - Management of bleeding gastroduodenal ulcers.

PMID- 11978994
TI  - Introduction. Complications in hepatobiliary surgery.

PMID- 11978995
TI  - A bleeding liver tumor. Case report.

PMID- 11978996
TI  - Management of spontaneous rupture of liver tumours.
AB  - Spontaneous ruptures of a liver tumour are often considered as a potentially life
      threatening situation. The aim of the present study was to evaluate both clinical
      features and treatment in a subgroup of patients with ruptured liver tumours.
      From 1995 to 2000, 20 patients were referred to our centre for spontaneous
      rupture of a liver tumour associated with haemoperitoneum. Hepatocellular
      carcinoma (HCC) was present in 13 patients (11 men and 2 women) aged from 48 to
      72 years (mean 62) and adenoma in 7 women aged from 23 to 52 years (mean 35).
      Although all patients experienced sudden abdominal pain and anaemia, shock at
      admission was present in 4 (20%) patients including 3 with HCC. In patients with
      HCC, severe liver insufficiency (Child-Pugh C) was present in 5 cases including
      the 3 shocked patients. No treatment was undertaken in 2 patients, transarterial
      embolization was performed in 9 cases and 5 patients underwent delayed resection.
      In hospital, mortality was observed in 3 (23%) patients, all of them had severe
      liver insufficiency. Long-term survival was observed in patients with good liver
      function who underwent resection. In patients with adenoma, shock at admission
      was observed in only 1 patient under anticoagulation treatment. Emergency
      resection was performed in 3 cases. A decrease of the tumour size was observed in
      patients who underwent delayed resection resulting in a lower rate of peri
      operative transfusion. In conclusion, this study confirms that the majority of
      patients with ruptured liver tumours had no evidence of haemodynamic instability
      and therefore should be initially managed conservatively. In patients with single
      ruptured HCC associated with good liver function, long-term survival can be
      observed after liver resection. Delayed resection facilitated the operative
      procedure in patients with ruptured adenoma.

PMID- 11978997
TI  - Complicated laparoscopic cholecystectomy. A case report.

PMID- 11978998
TI  - Management of bile duct injuries: treatment and long-term results.

PMID- 11978999
TI  - Introduction. Complications of pancreatic surgery and pancreatitis.

PMID- 11979000
TI  - Management of acute pancreatitis. Case report.

PMID- 11979002
TI  - Leakage after pancreaticoduodenectomy. Case report.

PMID- 11979001
TI  - Recent developments in the management of acute pancreatitis.

PMID- 11979003
TI  - Complications of pancreatic cancer resection.
AB  - Pancreatic cancer is a common cause of cancer death in the developed world.
      Currently, resection is the only chance of long-term survival. The post-operative
      mortality in nonspecialist centres often exceeds 20% but is around 6% or less in
      specialist centres. The overall complication rate even in specialist centres is
      18-54%. An analysis of eleven large series of pancreatic resections shows an
      incidence of common complications of 10.4% for fistula, 9.9% for delayed gastric
      emptying, 4.8% for bleeding, 4.8% for wound infection and 3.8% for intra
      abdominal abscess. The median hospital stay is 13-18 days in different series.
      The re-operation rate varies from 4 to 9% with a mortality rate of 23 to 67%.
      Major complications are a significant factor in post-operative mortality,
      especially if they require re-operation. The use of octreotide or somatostatin to
      prevent complications is supported by several multicentre, double-blind,
      randomized controlled trials. The best way to improve outcome is to concentrate
      pancreatic cancer care in regional specialist centres.

PMID- 11979006
TI  - Compulsory treatment - what do we know and where should we go?

PMID- 11979005
TI  - Colorectal surgery and anastomotic leakage.

PMID- 11979004
TI  - Complicated diverticulitis. Case report.

PMID- 11979007
TI  - Therapy instead of punishment for drug users - Germany as a model?
AB  - Germany underwent a sociolegal process from strict drug prohibition to a multi
      focus approach: harsh repression of drug supply and specific treatment against
      consumption. Criminal law now opens pathways to four different manners of demand
      reduction by treatment: commitment to closed forensic hospitals, combination of
      probation or parole with a treatment order, treatment within penitentiaries and
      deferring indictment or punishment in favour of treatment. Although each of these
      modalities represents coerced treatment, the methods are diverse and can be of
      the drug-free or maintenance type as well as in- or out-patient treatment.
      Evidently there are conceptual and implementation problems to each of these
      strategies. But all in all they represent the insight that drug behaviour can
      only be changed by public health measures rather than by criminal law as such.

PMID- 11979008
TI  - Compulsory drug treatment in Canada: historical origins and recent developments.
AB  - In Canada, illicit drug use and addiction have traditionally been considered as a
      criminal justice problem and have been addressed from a legal perspective. Over
      the past century, a medical approach to drug addiction has slowly crept into the
      criminal justice processing of drug offenders. This has happened through the
      combination of principles of punishment with principles of addiction treatment in
      the sentencing of drug offenders to create a distinct application of 'compulsory
      drug treatment' in Canada. However, this evolution has occurred sporadically over
      time, with punishment and coercion as predominantly the main approach to dealing
      with this population. This evolution has recently culminated in Canada with the
      development of two criminal justice approaches to dealing with the substance use
      problems of drug offenders that incorporate concepts of punishment and treatment
      more equally than ever before - conditional sentencing and drug courts. This
      paper outlines the historical evolution of concepts of 'compulsory treatment',
      discusses such examples of contemporary 'compulsory treatment' as conditional
      sentencing and drug courts, and analyses the implications, concerns and
      challenges associated with these tools currently used in the sentencing of drug
      offenders in the Canadian context.

PMID- 11979010
TI  - Modes and impact of coercive inpatient treatment for drug-related conditions in
      Switzerland.
AB  - BACKGROUND: Two forms of institutionalized pressure to treatment can be
      distinguished in Switzerland: civil commitment and court referral. In court
      referral, the referred patient has the right to refuse treatment. OBJECTIVES: To
      compare court referrals for inpatient treatment to voluntary therapy. METHODS:
      Comparison of interviews at treatment entry and discharge records. RESULTS: There
      were few systematic differences at entry except for voluntary subjects having had
      less contact with the legal system before treatment, independently of the
      specific court referral. At discharge, voluntary patients had a better social
      integration and fewer legal problems. DISCUSSION: Legal problems waiting for
      court referrals at discharge may be a significant handicap for reintegration.
      Otherwise, voluntary patients and court referrals showed few systematic
      differences in inpatient treatment.

PMID- 11979009
TI  - Sweden: integrated compulsory treatment.
AB  - In the year 2000, 804 adults were in coercive care for a maximum of 6 months
      under the Swedish Act on Care of Addicts in Certain Cases, which has both
      paternalistic and utilitarian motives. The extensive rights of the state to
      intervene in the private lives of its citizens seem to have a solid support in
      society. The article describes the present system and offers some explanations
      for its acceptance by looking at history. The fact that compulsory decisions have
      been made within the social administration has meant that such measures grew with
      the welfare system and could benefit from its goodwill. The medical profession
      provided motivation for preventive compulsory measures for social or individual
      reasons and gave hope for a cure. The crucial involvement of laypersons and non
      governmental organisations in decision-making and provision of compulsory
      treatment has given compulsory treatment a high political legitimacy. Compulsion
      became 'internalised' in the Swedish society. The economic and political
      liberalisation of today may pose a threat to the Swedish compulsory treatment of
      substance misusers.

PMID- 11979011
TI  - Compulsory substance abuse treatment: an overview of recent findings and issues.
AB  - An overview of research trends and issues in the area of compulsory substance
      abuse treatment is presented, using a sample of 170 English-language articles
      obtained from a search of 4 databases (Medline, PubMed, Embase, PsychINFO,
      supplemented by a manual search). About half (51%) of these articles were non
      empirical (i.e. literature reviews, policy proposals, legal and ethical
      commentaries on compulsory treatment). A subsample of empirical studies published
      since 1988 (n = 71) was coded to summarize research trends in relation to 3 key
      issues: (1) how compulsory treatment was studied (country of origin; type of
      compulsory treatment; treatment population), (2) the evidence base for judging
      effectiveness of compulsory treatment (research design; sampling; type, timing
      and results of outcome measures), and (3) the relationship between compulsory
      treatment and coercion (measurement strategies). Directions for future research
      are discussed.

PMID- 11979012
TI  - 'Getting checked and having the test': drug injectors' perceptions of HIV testing
      - findings from qualitative research conducted in England.
AB  - If HIV and AIDS policy initiatives are to be successful in tackling the spread of
      infection it is important to understand more about the ways in which people
      perceive HIV and AIDS. HIV testing is a policy initiative that will work when
      people take the test and make appropriate changes to their behaviour as a result.
      This paper is based on a study that used in-depth interviews and a vignette with
      drug injectors to explore drug injectors' perceptions of HIV risk outside and
      inside prison. HIV testing was an integral part of drug injectors' perceptions of
      risk. Three main themes emerged from the analysis of these data: first, reasons
      for not taking a test; second, reasons for taking a test; and third, the impact
      of testing upon subsequent behaviour. The paper ends with a summary and
      conclusions highlighting implications for future research and policy development.

PMID- 11979013
TI  - Three-year follow-up study of heroin users in Bratislava.
AB  - The principal goal of the present study was to find out the prospects of patients
      who enter a treatment facility due to their opioid dependence in the specific
      socioeconomic conditions of a transforming Central European country. The
      prospective follow-up study of a cohort of 351 patients, 76% males and 24%
      females, with an average age of 21.5 years (SD 4.8 years) was evaluated 1 and 3
      years after the patients were taken into treatment. The treatment intake was
      performed in a specialized comprehensive treatment facility in Bratislava, Slovak
      Republic. One and 3 years later, 79 and 70% of the patients, respectively, were
      contacted. The results show that after 3 years, 30% of patients (106) had been
      fully abstinent from all opioids for at least 6 months, 6% (19) had been
      abstinent less than 6 months, 10% (35) were on substitution treatment and 25%
      (86) were regular heroin users at that time. A significantly better outcome after
      3 years was observed among those subjects who were at work or at school at the
      time of admission. Despite different socioeconomic conditions, the results
      demonstrate that findings concerning the outcome of opiate users undergoing
      treatment are consistent with those from other parts of the world.

PMID- 11979015
TI  - Natural course of preclinical type 1 diabetes.
AB  - The clinical presentation of type 1 diabetes is preceded by an asymptomatic
      latent period characterized by the presence of diabetes-associated autoantibodies
      in the peripheral circulation, reflecting beta-cell damage. This prediabetic
      period may last for months and years. Several studies observing genetically
      susceptible subjects from birth have shown that insulin autoantibodies (IAA) are
      the first or among the first autoantibodies to appear in young children, implying
      that insulin may be the primary autoantigen in most cases of childhood type 1
      diabetes. About 12-16% of siblings of children with type 1 diabetes have been
      observed to test positive for at least one diabetes-associated autoantibody,
      whereas the risk of diabetes among siblings has been estimated to be 6-8%. In
      parallel, close to 4% of Finnish schoolchildren tested positive for at least one
      diabetes-associated autoantibody; the lifetime risk of type 1 diabetes in the
      Finnish population has been estimated to be close to 1%. These observations
      suggest that only 25-50% of those with signs of beta-cell autoimmunity eventually
      progress to clinical type 1 diabetes. Accordingly there is a considerable
      proportion of children in whom beta-cell autoimmunity remains subclinical or is
      aborted. Positivity for only one diabetes-associated autoantibody may actually
      represent innocent beta-cell autoimmunity, while positivity for two or more
      autoantibodies seems to mark a point of no return. The autoimmune response is
      very dynamic in the early phase of prediabetes, with spreading from one antigen
      to another and from one epitope to another within a given antigen. In addition
      both isotype spreading and switching can be observed in early prediabetes. This
      indicates that the early prediabetic process may be a suitable target for
      immunomodulation aimed at delaying or preventing progression to clinical
      diabetes.

PMID- 11979016
TI  - To screen or not to screen for pre-type 1 diabetes?
AB  - The incidence of type 1 diabetes is increasing worldwide and the disease is an
      onerous burden both to the individual and to society. There are thus important
      reasons to screen for the disease before it becomes manifest: (1) to improve
      understanding of the natural history of the prediabetic period; (2) to gain
      further insights into the immunopathogenesis of the disease; (3) to identify
      individuals for prevention trials; (4) to make an earlier diagnosis in order to
      reduce morbidity and mortality. Great strides have been made, yet there is still
      a great deal to be learned. Opponents of screening argue that screening tests for
      the disease have a low positive predictive value and that predicting the disease
      without a primary prevention capability raises ethical considerations because of
      induced stress, lifestyle changes, cost and potential effects on insurability.
      The greatest single barrier against large-scale population screening and
      prevention of the disease remains the lack of an effective intervention. However,
      screening in the context of well-designed research studies must continue -
      ultimately the benefit to the individual and to society will be immense.

PMID- 11979014
TI  - Childhood diabetes: a global perspective.
AB  - Diabetes is an evolving disease, with changing patterns seen in both type 1 and
      type 2 diabetes. A wide (over 400-fold) variation exists in worldwide incidence
      rates of type 1 diabetes, with the highest occurring in Finland (over 45 per
      100,000 under the age of 15 years) and the lowest in parts of China. In many
      countries (e.g. in Europe, the Middle East, Australia) the incidence of
      autoimmune-mediated type 1 diabetes in children <15 years of age has risen by 2
      5% per annum. Type 2 diabetes is also increasing rapidly globally and is
      occurring at a younger age, including in adolescence and childhood. In the USA,
      approximately one third of newly diagnosed in the adolescent age group is type 2,
      with up to 20% presenting with ketosis and ketoacidosis. The management of type 2
      diabetes is especially difficult in the adolescent age group. Obesity is the
      single most obvious risk factor for type 2 diabetes. Lifestyle modification
      programmes starting in childhood are urgently needed and society needs to change
      its attitudes to childhood nutrition, play and exercise.

PMID- 11979017
TI  - The present status of intervention trials.

PMID- 11979018
TI  - Type 2 diabetes in children: clinical aspects and risk factors.
AB  - In the past, type 2 diabetes mellitus was considered a disease of adults and
      older individuals, not a paediatric condition. Over the last decade, however, in
      the USA and the rest of the world there has been a disturbing trend of increasing
      cases of type 2 diabetes in children, mirroring increasing rates of obesity. The
      risk factors for paediatric type 2 diabetes are: (1) obesity and increased body
      mass index; (2) family history of type 2 diabetes; (3) membership of ethnic
      minority; (4) puberty (mean age of diagnosis is approximately 13.5 years); (5)
      female gender; and (6) features of 'syndrome X'. The common link among these risk
      factors is insulin resistance, which plays a pivotal role in the pathophysiology
      of type 2 diabetes. Both insulin resistance and beta-cell failure are present in
      the fully established diabetes state. Data will be presented on how these risk
      factors impact on insulin sensitivity and insulin secretion in childhood,
      ultimately leading to type 2 diabetes. The clinical presentation of type 2
      diabetes in children and its distinction from type 1 diabetes will be discussed.

PMID- 11979019
TI  - Maturity-onset diabetes of the young (MODY): genetic and clinical
      characteristics.
AB  - Maturity-onset diabetes of the young (MODY) is a genetically and clinically
      heterogeneous subtype of familial diabetes mellitus characterized by early onset,
      autosomal dominant inheritance and primary defects of insulin secretion.
      Mutations in six genes cause most of the MODY cases. These genes encode the
      enzyme glucokinase and the transcription factors hepatocyte nuclear factor
      4alpha, hepatocyte nuclear factor 1alpha, insulin promoter factor-1, hepatocyte
      nuclear factor 1beta and neuroD1. Additional MODY genes remain to be identified.
      The study of families with MODY has shown that the different MODY subtypes
      present different metabolic and clinical profiles.

PMID- 11979020
TI  - Children with type 2 diabetes: the risks of complications.
AB  - Type 2 diabetes is an increasing problem in children. Two decades ago it had been
      described only in selected groups, e.g. the Pima Indians. Childhood type 2
      diabetes appears to be similar to the metabolic syndrome in adults and is
      characterized by obesity, hyperglycaemia and insulin resistance. It can present a
      diagnostic challenge in children, as they can present with diabetic ketoacidosis;
      the measurement of autoantibodies and C-peptide levels may be helpful. The
      logarithmic association between the risk of complications with increasing
      glycaemia which has been established for adults with type 2 diabetes is likely to
      hold true for children but the conclusions of trials in adults must be
      extrapolated with caution. Little is known about the onset and progression of
      macrovascular disease in affected children but it is almost certain that they
      will develop an excess of premature cardiovascular disease. However, the
      importance of reducing glycaemia in younger adults with diabetes, in order to
      minimize the incidence of microvascular complications, has been unequivocally
      demonstrated in the Diabetes Control and Complications Trial (DCCT). Diet and
      exercise have a major role to play in the treatment and prevention of type 2
      diabetes in children as well as adults - the escalation of type 2 diabetes
      throughout the developed world is a major public health problem. Extrapolating
      data from adults, metformin appears to be the logical first-line treatment in
      children with type 2 diabetes; sulphonylureas are also used but neither of these
      agents have been evaluated in trials in children and are not licensed for such
      use. With regard to other newer agents, it seems wise to use well-established
      drugs with a long track record and for which the long-term safety data are
      available.

PMID- 11979021
TI  - Insulin analogues - state of the art.
AB  - The use of insulin analogues is rapidly expanding. At present, there are two
      short-acting analogues available for practical use, insulin aspart and insulin
      lispro, and one long-acting analogue, insulin glargine. Another long-acting
      analogue, insulin detemir, is still under development. The time action profile of
      short-acting analogues is both much more rapid and shorter than that of human
      insulin; the prominent feature of the long-acting analogues is their peakfree and
      fairly constant action. Insulin analogues offer alternative options for the whole
      spectrum of insulin therapy in type 1 and type 2 diabetes patients. The
      perception by many patients is strikingly positive, in particular regarding the
      overall quality of life. In objective efficacy terms, however, the potential to
      improve the degree of metabolic control appears to be only minor, yet
      demonstrable, provided the analogues are used according to their specific time
      action profile. This ensured, analogues are instrumental in minimizing the side
      effects of insulin therapy, i.e. the risk of (nocturnal) hypoglycaemia or
      problems with body weight control. Although there are no indications of safety
      concerns with insulin analogues, the availability of long-term outcome data based
      upon observations in human patients would be very valuable.

PMID- 11979022
TI  - Experience with insulin analogues in children.
AB  - Current data on rapid and long-acting insulin analogues in the paediatric age
      group is limited. While several studies indicate a benefit in reducing
      hypoglycaemia, particularly at night, with rapid or long-acting insulin analogue
      treatment, the effect on long-term glycaemic control remains controversial. The
      continuous glucose monitoring system offers a new option for tailoring treatment
      with insulin analogues to achieve optimal glycaemia. In 29 adolescents with
      diabetes this approach confirmed the non-inferiority of postprandial rapid-acting
      analogue administration compared to preprandial regular insulin, but revealed
      significant mealtime differences, with increased analogue requirement at
      breakfast and dinner. Although rapid- and long-acting insulin analogues may offer
      potential benefits for problems frequently encountered in paediatric diabetology,
      their value for the individual child still has to be tested in long-term
      observations in daily clinical practice.

PMID- 11979023
TI  - Islet cell transplantation and other new technologies for treating type 1
      diabetes: a paediatric view.
AB  - Recent advances in diabetes care have facilitated the achievement and maintenance
      of excellent metabolic control. New insulin pumps and continuous glucose
      monitoring systems provide cause for optimism that an artificial pancreas may
      soon be developed. In addition, transplantation biology has advanced to the point
      where pancreas and islet transplants are being performed with increasing
      frequency. Recent reports suggest that improved techniques for isolation of
      islets and immune suppression may allow these procedures to become more
      commonplace. However, serious questions regarding long-term safety and efficacy
      need to be answered in older individuals before consideration is given to their
      more routine use in children and adolescents with diabetes.

PMID- 11979024
TI  - Educational and psychosocial aspects of childhood diabetes: introduction to
      workshops.

PMID- 11979025
TI  - How do we educate young people to balance carbohydrate intake with adjustments of
      insulin?
AB  - The dietary management of childhood diabetes is complex. Is it possible to
      educate young people to balance carbohydrate with their insulin? Can dietary
      knowledge be translated into lasting behaviour change? Do present teaching
      methods provide the skills necessary for children and parents to adjust their
      insulin therapy adequately? Evidence shows great variation in glycaemic control
      between centres and countries but the impact of dietary education methods is
      poorly evaluated and its links with clinical and psychosocial outcomes is
      virtually unknown. There is also little evidence to suggest cohesive teamworking
      with clear dietary targets for glycaemic control, lipids, incidence of
      hypoglycaemia, compliance, effect on peer and sibling relationships, and
      evaluation of individual dietary components, e.g. fibre, fat, antioxidants. There
      is wide variation in methods of dietary education, which are often based on
      historic practice. They include rigid counting of grams of carbohydrate,
      carbohydrate portion assessments, qualitative diets, low glycaemic index diets
      and the more recent 'intensified' carbohydrate measures with daily adjustments of
      insulin (the basis also of pump management). This last method has many benefits
      although it requires extensive nutrition education, it allows greater flexibility
      and variety of food intake, is sensitive to the varying daily energy expenditure
      of childhood and it addresses postprandial glycaemic excursions, all of which are
      inadequately managed by conventional therapy. However, one of the problems of
      overemphasizing carbohydrate measurement is that total carbohydrate intake may be
      suppressed, with a resulting increase in fat, this may contribute to an increase
      in cardiovascular risk. The ISPAD Consensus Guidelines 2000 contain dietary
      recommendations but scientific evidence is often lacking. Limited dietary studies
      show that some countries can meet guidelines more successfully than others. There
      are many reasons for this, such as food availability, types of food eaten, food
      preferences and family/cultural/religious influences. Educational methods must be
      adapted to local customs. Is there enough evidence to recommend a particular
      dietary education method? What outcomes do we hope to achieve? The workshop
      explored these issues in order to develop a deeper understanding of the
      complexity of dietary modification in childhood diabetes.

PMID- 11979026
TI  - How do we organize smooth, effective transfer from paediatric to adult diabetes
      care?
AB  - Transition from paediatric to adult care is a major milestone in the life of a
      young person with diabetes, yet it is commonly poorly done. This finding is
      supported by the dearth of publications in the literature that particularly
      relate to transition in diabetes care. Other transitions occur at this time of
      life, for example: from parental supervision to growing independence and from
      secondary school to post-school options. Health professionals know, from
      anecdotal evidence, that this is the period when young people with diabetes 'drop
      out' of the system. They often have no specialist follow-up and attend only the
      primary care physician for insulin prescriptions. Then, inevitably, a problem
      occurs that cannot be managed by the family doctor, such as diabetic ketoacidosis
      or pregnancy, and the patient is finally referred to an adult unit. There are
      many contributing factors to poor transition but two major reasons are that
      members of this age group are classic non-attenders and, importantly, they have
      not been well prepared for the transition. Preparation is the key to success and
      this must include parents as well as the young person. Components of transition
      preparation include: self-advocacy, independent health care behaviours, sexual
      health, psychosocial support, education and vocational planning, and health and
      lifestyle (drugs, alcohol, etc.). Considerable differences exist between many of
      the paediatric and adult services, and this cultural shift has significant impact
      on the success or otherwise of transition. Paediatric care is often
      multidisciplinary, family focused, prescriptive and requires parental direction
      and consent. Adult care is often provided by a single doctor, is patient focused,
      more investigational and requires autonomous, independent skills on the part of
      the user. Young people and their families, unless well prepared, become confused
      and disillusioned with the adult system. To avoid this situation, there is a
      variety of solutions, including adolescent transition clinics attended by both
      paediatric and adult teams, a transition coordinator who is responsible for
      making the transfer as smooth as possible, etc. Unfortunately, the very nature of
      the group in question means that none of these solutions is perfect. In reality,
      transition is a process that takes place over a number of years and should not be
      considered an event. The transition process needs to begin in early adolescence,
      to foster independence and communication skills, and to incorporate health
      education.

PMID- 11979027
TI  - Self-efficacy and diabetes: why is emotional 'education' important and how can it
      be achieved?
AB  - Adequate age-appropriate diabetes knowledge and skills are essential to the
      success of diabetes self- and parental care. Health professionals have a central
      role in providing diabetes education. A direct link between diabetes knowledge
      and diabetes regimen behaviour cannot be assumed. Health professionals have to
      help children and their parents to develop the emotional concept of 'self
      efficacy for diabetes self-care', to ensure optimal diabetes control.

PMID- 11979028
TI  - How can we adapt education for children across different countries?
AB  - The development of educational material as part of major changes in the service
      of the diabetic clinic in Glostrup University Hospital turned out to be a very
      rewarding process for the multidisciplinary team. This material includes age
      appropriate goals and guidelines for teaching and learning about diabetes, and
      advice on coping with diabetes in hand-outs designed for diabetic educators,
      parents/adults and teenagers. The paper briefly describes the developmental
      process, the concepts and designs of the material, and makes recommendations on
      how it can be applied. Part of the material was later translated into Polish and
      Russian in connection with educational projects in these countries, and the
      material as a whole was recently incorporated into the Novo Care website at
      www.d4pro.com - Childhood Diabetes. Growing Internet access by diabetes patients,
      their relatives and health care professionals creates almost overwhelming
      possibilities, but also brings up many new questions. The development of diabetes
      educational material of the more 'traditional' type is discussed with regard to
      content, ideas and design, and focuses on how these concepts and projects can be
      influenced and adapted across different countries by Internet communication.

PMID- 11979029
TI  - Cross-cultural differences in the management of children and adolescents with
      diabetes.
AB  - Glycaemic control deteriorates frequently in adolescents with diabetes. There is
      a considerable body of work on the effect of psychological aspects of management
      in this age group, but few randomized controlled trials of the effect of specific
      behavioural therapy and lifestyle modification on the improvement of glycaemic
      control. Of recent interest have been the observations from the Hvidore Study
      Group on cross-cultural differences in glycaemic control. The average
      glycosylated haemoglobin in 22 centres, across 18 countries, varied in young
      people, with HbA1c levels ranging from 7.6 to 10.2%. No obvious differences in
      management were identified in this survey that could account for the disparities
      in glycaemic control. Data from the Scottish Study Group demonstrated similar
      variation in average glycaemic control in centres across a single culture. Using
      the qualitative methodology of anthropological research, some specific factors
      were identified that appear to influence young people's response to diabetes
      management and strategies employed by health professionals in their advice and
      care of the diabetes, particularly in relation to intensive insulin regimens. The
      main cultural factors influencing glycaemic control appear to be communication,
      reciprocal support between young people and professional heart carers and family
      structure within an individualistic, as against an egalitarian, society. Shared
      beliefs about teenage risk behaviour together with the medicalization of
      adolescence within medical culture also appears to be highly influential. The aim
      of this educational discussion group was to explore how a variety of health care
      professionals from distinctive cultures approach diabetes care delivery in this
      age group. The specific success and difficulties in different cultures in
      managing the young person with diabetes were investigated. Also discussed was how
      qualitative research methodology may generate further research in this area.

PMID- 11979030
TI  - Recurrent diabetic ketoacidosis: causes, prevention and management.
AB  - Longitudinal studies indicate that 20% of paediatric patients account for 80% of
      all admissions for diabetic ketoacidosis (DKA). The frequency of DKA peaks during
      adolescence and, although individuals generally go into remission, they may
      continue to have bouts of recurrent DKA in adulthood. The evidence for insulin
      omission being the behavioural precursor to recurrent DKA is reviewed and
      discussed. Thereafter the range of possible psychosocial causes is explored and
      the evidence for each discussed. Approaches to assessing the individual and their
      family to identify aetiology and therefore appropriate intervention are
      considered and treatment options reviewed. Finally, the paper examines potential
      risk factors for recurrent DKA, possible strategies for identifying these early
      and how to use these assessments to prevent subsequent recurrent DKA.

PMID- 11979031
TI  - Continuous monitoring of blood glucose.
AB  - Continuous blood glucose monitoring aims to: better evaluate glycaemic
      variations; better detect hypoglycaemia; and, ultimately, automatize insulin
      delivery (artificial beta cell). The sensors can be fully implantable, with the
      challenge of constructing durable systems to avoid repeated implantations. In
      dwelling needle-like electrodes and microdialysis fibres with a pump that brings
      the dialysate to the glucose sensor are inserted in the subcutaneous tissue
      through the skin. The GlucoWatch is an almost non-invasive technique that
      extracts the extracellular fluid by iontophoresis. In these systems, the glucose
      oxidase generates the electrical signal, proportional to the glucose
      concentration. Non-invasive techniques aim at measuring the glucose concentration
      without breaching the skin, using absorption of light in the infrared spectrum.
      These techniques have not reached the necessary reliability for use as glycaemic
      alarms, and even less as artificial beta cells. Currently, glucose sensors are
      mainly used as glycaemic holters to help in the management of insulin therapy.

PMID- 11979032
TI  - Hypoglycaemia and counterregulation during childhood.
AB  - Hypoglycaemia is particularly common in young children with type 1 diabetes
      mellitus yet the normal protective counterregulatory responses have been little
      studied in this age group. The studies reported have shown conflicting results,
      in part related to prior glycaemic control and also to the method of
      investigation used. Counterregulatory hormone responses during both spontaneous
      and experimentally induced episodes of nocturnal hypoglycaemia do appear to be
      blunted, which may be a function of sleep itself. Although studies of cognitive
      function have consistently shown defects in certain areas of neurocognitive
      performance, particularly in those children with early-onset diabetes or a prior
      history of severe hypoglycaemia, the contribution of nocturnal hypoglycaemia to
      the development of these impairments has not been evaluated. In young adults and
      adolescents, nocturnal hypoglycaemia has been linked to cardiac arrhythmia and
      the risk of sudden death. The development of new techniques for continuous
      subcutaneous glucose monitoring may allow detailed study of counterregulatory
      responses and symptom recognition in young children. Effective intensification of
      insulin therapy without an increased risk of hypoglycaemia may be possible using
      new insulin analogues or continued subcutaneous intravenous infusion (CSII), thus
      improving patient compliance and overall quality of clinical care.

PMID- 11979033
TI  - Current issues in paediatric diabetology: introduction to Meet-the-Expert
      sessions.

PMID- 11979034
TI  - Insulin treatment at onset of diabetes. Leicester Royal Infirmary Children's
      Hospital, Leicester, UK.
AB  - Management strategies and practicalities of insulin therapy in the first days and
      weeks after the diagnosis of diabetes in children and adolescents depend on the
      clinical situation and the facilities available. Outpatient or domiciliary
      management favoured by some centres is only practicable and safe if an
      experienced team is readily available. There is evidence showing a correlation
      between the level of glycaemic control achieved in the earliest years of
      treatment and the metabolic control in subsequent years (the 'tracking
      phenomenon'). The major factors influencing metabolic control in the first year
      after diagnosis certainly include the continuing secretion of endogenous
      pancreatic insulin. There has been considerable debate as to whether continuing
      insulin secretion and the induction of the remission phase can be significantly
      affected by the methods of insulin administration in the first days after
      clinical diagnosis; whether intravenous insulin has a protective effect; whether
      psychosocial factors have a more profound influence on metabolic control; and
      whether there is enough evidence to make valid recommendations on the optimal
      method(s) for treating children at the onset of diabetes. It seems likely that
      from the first day after diagnosis benefit is derived from attempting to obtain
      near normoglycaemia and the rapid induction of a partial remission phase by
      whatever insulin regimen is found to be most successful. This may occur not only
      by reducing the threat of glucotoxicity on the beta-cells but also by setting a
      pattern of optimal control for the child and the family. This process is enhanced
      by frequent contact with the team of experts in childhood diabetes who are able
      to give advice on insulin adjustments from the onset of diabetes.

PMID- 11979035
TI  - Coeliac disease in children and adolescents with type 1 diabetes mellitus: to
      screen or not, to treat or not?
AB  - Coeliac disease is more prevalent in individuals with type 1 diabetes mellitus
      than in the normal population. It often presents in an atypical or silent form.
      Specific autoantibodies are found in almost all cases. Untreated coeliac disease
      may be associated with long-term health risks, so screening and early treatment
      with a gluten-free diet seem to be justified. However, extended follow-up is
      needed to document the clinical benefits of screening and treatment in diabetic
      patients.

PMID- 11979036
TI  - Selection for and initiation of continuous subcutaneous insulin infusion.
      Proceedings from a workshop.
AB  - Continuous subcutaneous insulin infusion (CSII) has been used in the paediatric
      age group for more than 20 years. The technique is not yet widely used in most
      countries but there has recently been increasing interest in pump therapy for
      young children and adolescents. In 1999, 7.5% of Swedish children and adolescents
      with diabetes used pumps, now the figure is approaching 12%. The indication for
      starting pump therapy has usually been a medical problem, but today quality of
      life issues are becoming increasingly important. One technique sometimes used is
      to start CSII by wearing the pump only at night. Daily insulin requirements are
      usually decreased compared with injection therapy. Studies have shown that it is
      possible to lower HbA1c when using an insulin pump and that the risk of severe
      hypoglycaemia can be lowered. The use of CSII has also been successful in
      preventing recurrent admission for diabetic ketoacidosis. While starting pump
      therapy does take an extra effort from both the diabetes team and the family,
      routine visits are generally no more time-consuming than for patients on multiple
      injection therapy. CSII can be initiated during admission to hospital but most
      pumps are started on an outpatient basis. Our department has the patients on the
      day care ward for 3-4 days of 'pump school'. Parents wear a saline pump for
      practice. The total daily insulin dose is usually lowered 15-20% compared with
      multiple injections; on average 40-50% (sometimes up to 60%) of the daily dose is
      given as basal rate. We start all pumps on rapid-acting analogues and use 40
      IU/ml if the basal rate is <0.3 IU/h. In conclusion, the use of CSII in children
      and adolescents is well accepted and can be managed safely.

PMID- 11979037
TI  - The quality circle: how to improve the outcome of paediatric diabetes care.
AB  - Most multicentre studies demonstrate that the outcome of diabetes therapy falls
      below the targets set up in recent guidelines. Applying quality control
      methodology may provide one means better to achieve such targets. Before setting
      up a quality circle, objective, standardized documentation of relevant quality
      indicators is necessary. Based on internal (for example longitudinal changes over
      time) and external quality control (comparison with other institutions), both
      favourable and unfavourable results achieved by each institution are identified.
      Such data provide the basis for intensive discussion among the members of
      diabetes care teams on how to remedy such deficits. In Germany, the working group
      on paediatric diabetology set up a system for external quality assessment in
      1995: For 6 continuous years, quality indicators are compared twice yearly, and
      regional quality circles for more open discussions have been established, in
      addition to yearly nationwide meetings among all participants.

PMID- 11979039
TI  - Screening for vascular complications in children and adolescents with type 1
      diabetes mellitus.
AB  - Type 1 diabetes mellitus poses a significant health burden, particularly as a
      result of its microvascular complications. Clinically evident diabetes-related
      microvascular complications are extremely rare in childhood and adolescence.
      However, early functional and structural abnormalities may be present a few years
      after the onset of the disease. Therefore, regular screening for diabetic
      microvascular disease, particularly retinopathy and nephropathy, are of foremost
      importance in paediatric diabetes care. Early detection of diabetic
      microangiopathy and timely treatment of early signs of these complications have a
      pivotal role in prevention of blindness and end-stage renal failure in children
      and adolescents with diabetes.

PMID- 11979038
TI  - Diabetes and the internet.
AB  - This paper examines what the World Wide Web has to offer patients, families and
      professionals in relation to diabetes. The potential pitfalls and dangers are
      discussed, leading to a wider debate on how the Internet can be expected to
      impact upon diabetes and other health care provision in the near future, and how
      health care professionals' practices will have to change. Themes include: the
      World Wide Web (finding material, assessing authenticity, pitfalls for patients,
      personalized pages, chat rooms, security); e-mail consultation (benefits, risks,
      minimizing risk, what to tell patients, legal constraints, security);
      telemedicine (telemetry, surveillance, security); search engines (journals,
      etc.); looking ahead (digital television, web-based medical records).

PMID- 11979040
TI  - Findings from the Hvidore Study Group on Childhood Diabetes: metabolic control
      and quality of life.
AB  - The study involved 2,101 adolescents, aged 10-18 years, from 21 centres in 17
      countries in Europe, Japan and North America. Adolescent quality of life (QOL)
      was assessed by a previously developed Diabetes Quality of Life Questionnaire for
      adolescents (DQOL), measuring impact of diabetes, worries about diabetes,
      satisfaction with life and health perception. Parents and health professionals
      assessed 'family burden' using newly constructed questionnaires. Mean HbA1c was
      8.7% (range 4.8-17.4%). Lower HbA1c was associated with lower impact (p <
      0.0001), fewer worries (p < 0.05), greater satisfaction (p < 0.0001) and better
      health perception (p < 0.0001) for adolescents. Girls showed increased worries (p
      < 0.01), less satisfaction and poorer health perception (p < 0.01) earlier than
      boys. Parent and health professional perceptions of burden decreased with age of
      adolescent (p < 0.0001). Lower HbA(1c) was significantly associated with better
      adolescent-rated QOL on all four subscales and with lower perceived family burden
      as assessed by parents and health professionals.

PMID- 11979041
TI  - Atopic eczema/dermatitis syndrome and Malassezia.
AB  - Atopic dermatitis is a chronic multifactorial inflammatory skin disease, which
      has had a marked increase in prevalence during the last decades. Recently, a new
      nomenclature was recommended where the term 'atopic eczema/dermatitis syndrome'
      (AEDS) should be used to reflect the heterogeneity in this group of patients and
      where those patients without measurable IgE reactivity should be classified as
      either 'nonallergic AEDS' or 'non-IgE-associated allergic AEDS'. For nearly 20
      years it has been discussed whether the opportunistic yeast Malassezia,
      previously designated Pityrosporum, is a contributing factor to AEDS. Today there
      are several reports that demonstrate specific serum IgE or positive skin prick
      test and/or atopy patch test reactions to Malassezia in patients with AEDS.
      Several IgE-binding components have been identified in extracts of Malassezia
      ranging in molecular mass between 10 and 100 kD. The genes for nine Malassezia
      allergens with molecular weights ranging from 14 to 36 kD have hitherto been
      identified and cloned. Six of them are now produced by recombinant techniques and
      used in diagnostic tests. At present the genus Malassezia is subdivided into
      seven different species, which all have been isolated from human skin. The
      respective contribution of different Malassezia spp. to AEDS and in what
      proportion they share allergens remains to be clarified. We summarize here data
      that Malassezia can play a role in eliciting and maintaining eczema in patients
      with AEDS.

PMID- 11979042
TI  - Mouse models for the genetic dissection of atopy.
AB  - Atopic disorders are complex traits with a significant contribution of
      heritability. Several mouse models for atopic phenotypes such as allergen-induced
      and intrinsic asthma, atopic dermatitis and immediate cutaneous hypersensitivity
      have been used to systematically dissect the genetics of these diseases. Many of
      the chromosomal regions identified in genome-wide screens colocalize with linkage
      regions of autoimmune phenotypes suggesting common regulatory genes in
      combination (or addition) to disease-specific genes. Moreover, many of these
      regions correspond to regions found in the human system, thus strengthening the
      likelihood of a gene contributing to the phenotype. The role of individual
      candidate genes has been vigorously pursued in genetically modified mice by
      destruction or overexpression of the candidate gene. The complex interactions of
      multiple contributing genes may further be elucidated in randomly mutated mouse
      strains. Thus mouse models can contribute largely to the elucidation of disease
      genes.

PMID- 11979043
TI  - cDNA cloning and immunological characterization of a newly identified enolase
      allergen from Penicillium citrinum and Aspergillus fumigatus.
AB  - BACKGROUND: Penicillium citrinum and Aspergillus fumigatus are prevalent indoor
      airborne fungal species that have been implicated in human respiratory allergic
      disorders. It is important to understand the allergenic profile of these fungal
      species. The purpose of the present study is to characterize a newly identified
      enolase allergen from P. citrinum and A. fumigatus. METHODS: Fungal proteins were
      separated by two-dimensional (2D) gel electrophoresis and blotted onto
      polyvinylidene difluoride membranes. Protein spots that reacted with IgE
      antibodies in serum samples from asthmatic patients were identified and the N
      terminal amino acid sequences were determined by Edman degradation. The peptide
      sequences obtained were utilized in cloning the cDNA of the allergen genes by
      reverse transcriptase-polymerase chain reaction and the 5'- and 3'-rapid
      amplification cDNA end reactions. RESULTS: Our results from 2D immunoblotting
      identified a 47-kD IgE-reactive component in the extracts of P. citrinum and A.
      fumigatus. The N-terminal amino acid sequences of the 47-kD proteins are
      homologous to those of fungal enolases. The corresponding enolase cDNA from P.
      citrinum contains 1,552 bp and encodes a protein of 438 residues. In A.
      fumigatus, the isolated enolase cDNA has 1,649 bp and contains a 438-amino acid
      open reading frame. The deduced amino acid sequences of these two enolases have
      94% identity. These enolases from P. citrinum and A. fumigatus were expressed in
      Escherichia coli as a His-tagged protein and designated as rPen c 22 and rAsp f
      22, respectively. Sera from 7 (30%) of the 23 Penicillium-sensitized asthmatic
      patients showed IgE binding to the 47-kD P. citrinum component (Pen c 22) and
      rPen c 22. In addition, six of seven Pen c 22-positive serum samples have IgE
      immunoblot reactivity to the 47-kD A. fumigatus component (Asp f 22) and rAsp f
      22. A polyclonal rabbit antiserum generated against the N-terminal peptide of Pen
      c 22 can react with Pen c 22, rPen c 22, Asp f 22 and rAsp f 22. In addition, the
      presence of IgE cross-reactivity between rPen c 22 and rAsp f 22 and between
      enolases from A. fumigatus and Alternaria alternata was also detected by
      immunoblot inhibition. CONCLUSIONS: These results demonstrated that a novel
      enolase allergen from P. citrinum (Pen c 22) and A. fumigatus (Asp f 22) was
      identified. In addition, IgE cross-reactivity between enolase allergens from A.
      fumigatus and P. citrinum and between enolases from A. fumigatus and A. alternata
      was also detected. Results obtained provide more information on fungal enolase
      allergens.

PMID- 11979044
TI  - Development of the capacity of peripheral blood mononuclear cells to produce IL
      4, IL-5 and IFN-gamma upon stimulation with house dust mite in children with
      atopic dermatitis.
AB  - BACKGROUND: Imbalances of IL-4 and IFN-gamma production are widely known to
      increase IgE synthesis in allergic individuals, and IL-5 is known to play a
      critical role in the pathogenesis of various allergic diseases. However, little
      is known about how Th cells specific to house dust mite (HDM) develop the
      capacity to produce these cytokines in children with atopic dermatitis (AD).
      OBJECTIVE: This study aims to clarify when HDM-specific Th cells develop the
      capacity to produce IL-4, IL-5 and IFN-gamma in children with AD. METHODS: The
      production of IL-4, IL-5 and IFN-gamma by peripheral blood mononuclear cells
      (PBMCs) upon stimulation with HDM was measured in 91 children with AD and 37
      control subjects. The changes in the cytokine production with age were analyzed
      transectionally and longitudinally. RESULTS: IL-4 production by HDM-stimulated
      PBMCs in children with AD was already increased before age 1. Thereafter, it
      continuously rose until reaching a near-maximum level at age 2. Growth-related
      changes in the production of IL-5 resembled those in the production of IL-4 and
      peaked at age 1. The production of these cytokines was very low in control
      subjects up to age 2 and then gradually increased, albeit never above the levels
      measured in AD children. The production of IFN-gamma in children with AD reached
      a near-maximum level during the first year of life and diminished after age 3.
      Although IFN-gamma production in controls was lower than that in AD children
      during infancy, it continuously rose even after age 3 and surpassed the levels
      measured in AD children. The level of serum HDM-specific IgE antibody began to
      increase after age 1 following the rise of IL-4 production. Essentially the same
      relationship among IL-4, IFN-gamma and IgE synthesis was seen in a longitudinal
      study of 6 AD infants, in whom HDM-specific IgE was initially negative but later
      turned positive. CONCLUSIONS: These findings suggest that the capacity of HDM
      specific Th cells to produce IL-4, IL-5 and IFN-gamma develops and effectively
      matures during the first 3 years of life in children with AD.

PMID- 11979045
TI  - The role of interleukin-10 in the generation of CD4+ and CD8+ memory T cells
      (expressing a CD44+, CD62L- phenotype) and their contribution to the regulation
      of immunoglobulin E antibody formation.
AB  - BACKGROUND: Immunization of mice with low doses of protein antigens like keyhole
      limpet hemocyanin (KLH) results in high immunoglobulin (Ig) E Ab titers in the
      sera of those mice while the application of high doses leads to the production of
      only marginal amounts of IgE but high levels of IgG2a and IgG1 antibodies. The
      aim of these studies is to elucidate the role of interleukin-10 (IL-10) in the
      generation of memory T cells and their contribution to the production of IgE Ab.
      METHODS: Both IL-10-deficient mice and control mice were immunized repeatedly
      with KLH. Serum levels of KLH-specific Ab were measured. The frequencies of
      memory T cells were determined by flow cytometry and the role of CD4+ and CD8+ T
      cells was evaluated. RESULTS: IL-10-deficient mice show an augmented production
      of IgE in vivo. They exhibit enhanced ratios of CD4+:CD8+ memory T cells with a
      CD44+, CD62L- phenotype with a significantly raised generation of CD4+ memory T
      cells. On the other hand, the development of CD8+ memory T cells is reduced
      moderately in IL-10-deficient mice, which is an interesting fact since it has
      been shown that primed CD8+ T cells suppress IgE Ab production at least in vitro.
      The ratios of total CD4+:CD8+ T cells are augmented in IL-10-deficient mice
      compared to wild-type mice and in K01 mice compared to K100 mice in vivo.
      CONCLUSIONS: The elevated ratios of CD4+:CD8+ T cells indicate a higher capacity
      to provide B cell help, which results in a strongly elevated IgE response in IL
      10-deficient mice. These altered ratios are furthermore interesting in view of
      the regulatory role of CD8+ T cells which provide a suppressive potential
      regarding IgE Ab production as shown in vitro. The capacity of IL-10 to suppress
      IgE Ab production by reduction of the CD4+:CD8+ memory T cell ratio opens new
      possibilities in the interference with allergic disorders.

PMID- 11979046
TI  - Influence of maternal murine immunization with Dermatophagoides pteronyssinus
      extract on the type I hypersensitivity response in offspring.
AB  - BACKGROUND: Maternal exposure to environmental ubiquitous allergens could exert
      an influence on the newborn's immune repertoire and the later development of
      allergy. The aim of this study was to investigate the effects of maternal
      immunization with Dermatophagoides pteronyssinus (Dp) on the hypersensitivity
      response and IgG subclass production in offspring using a murine model. METHODS:
      A/Sn mice were immunized with Dp before mating with normal A/Sn males.
      Diaplacental serum samples were collected from newborn mice delivered by cesarean
      section, and maternal milk samples were extracted from the stomachs of newborn
      mice. Groups of offspring 25 or 45 days old were Dp immunized and boosted on the
      10th day after sensitization. The animals were bled 7 days after the booster.
      RESULTS: High levels of anti-Dp IgG subclasses - mainly IgG1, but also IgG2a and
      IgG2b - were transmitted by immunized mice via the placenta to the offspring. In
      the milk from immunized mothers, significant levels of anti-Dp IgG subclasses and
      anti-Dp IgM and IgA antibodies were detected. Moreover, the increase in total IgA
      antibodies in the milk of the immunized females correlated with a significantly
      increased level of TGF-beta1. TGF-beta2 levels were markedly higher than the
      beta1 isoform in the milk, although no difference was observed between the
      groups. When offspring from immunized mothers were sensitized at 25 days, a
      significant decrease in total and anti-Dp IgE antibodies as well as total and
      anti-Dp IgG1, IgG2a and IgG2b subclasses was observed compared to normal female
      offspring, whereas when offspring were sensitized at 45 days, both offspring
      groups showed similar levels of IgE and IgG subclasses. CONCLUSIONS: Our study
      showed that maternal immunization with Dp promotes the transference of specific
      antibodies and/or TGF-beta, which can negatively modulate the allergic response
      in offspring, and suggests that maternal preexposure to allergen before mating
      can protect mice during the early phase.

PMID- 11979048
TI  - Wasp venom rush immunotherapy induces transient downregulation of B cell surface
      molecule expression.
AB  - BACKGROUND: Little is known about the involvement of B cells in venom
      immunotherapy (VIT). To elucidate changes in the B cell phenotype during this
      process, we examined the expression of several surface molecules on peripheral B
      cells before and during VIT. METHODS: 15 venom-allergic patients with a history
      of systemic reactions after a wasp sting and venom-specific skin test reactivity
      as well as serum IgE were investigated before VIT (day 1), 1 day after reaching a
      maintenance dose of 100 microg (day 6) during inpatient rush VIT, and again on
      day 26 during continued outpatient maintenance therapy. Changes in the serum
      levels of total IgE, allergen-specific IgE (sIgE) and sIgG4 were measured by
      ELISA. Expression of several surface molecules on double-labelled B cells was
      studied by flow cytometry of peripheral blood mononuclear cells. RESULTS: Levels
      of total IgE, sIgE and sIgG4 showed a significant increase after 26 days of VIT.
      On day 6, cell surface expression of HLA- II-DR, CD5, CD32 and CD54 was decreased
      in intensity and numbers of positive cells compared to day 1, while on day 26,
      expression of these molecules approached again baseline levels. Furthermore, a
      trend to decreased CD23 was noted on day 6. No changes were observed for CD40,
      CD86, CD95 and HLA-I-ABC. CONCLUSION: These data show that during initiation of
      rush VIT, B cell expression of surface molecules involved in T-B cell cooperation
      and antigen presentation is downmodulated. B cells may thus be additional direct
      or indirect targets of high-dose antigen therapy and contribute to the
      persistence of TH1 responses during maintenance VIT treatment.

PMID- 11979047
TI  - Lipid A analogue, ONO-4007, inhibits IgE response and antigen-induced
      eosinophilic recruitment into airways in BALB/c mice.
AB  - BACKGROUND: Since antigen-specific IgE and eosinophils are major inducing factors
      of allergic inflammation of the airways, both factors are therapeutic targets of
      asthma. We investigated the effects of ONO-4007, a nontoxic lipid A analogue, on
      antigen-specific antibody response and the recruitment of eosinophils into
      airways in murine systems. METHODS: BALB/c mice were injected ONO-4007
      intraperitoneally during sensitization with ovalbumin (OVA) and aluminium
      hydroxide to determine its effects on the antigen-specific antibody response. ONO
      4007 was also injected intravenously during either systemic sensitization and
      inhalation with OVA, or sensitization or inhalation alone to determine its
      effects on antigen-induced airway inflammation. In vitro effects of ONO-4007 on
      the functional differentiation of naive CD4+ T cells were investigated by
      culturing naive CD4+ T cells derived from DO11.10 mice and OVA-pulsed dendritic
      cells (CDCs) with ONO-4007. RESULTS: ONO-4007 inhibited antigen-specific IgE and
      IgG1, but not IgG2a responses. ONO-4007 decreased the recruitment of eosinophils
      and the levels of IL-5 in bronchoalveolar lavage fluid, not only when it was
      injected during systemic sensitization and inhalation with OVA, but also during
      inhalation alone. ONO-4007 inhibited the differentiation of IL-4- and IL-13
      producing CD4+ T cells in vitro, which was partly mediated by DCs. CONCLUSIONS:
      ONO-4007 inhibited antigen-specific IgE and IgG1 responses and antigen-induced
      eosinophil recruitment into the airways in BALB/c mice. These effects were
      mediated, at least partly, by the modulation of DCs, although there may also be
      other mechanisms.

PMID- 11979049
TI  - Oligoclonal analysis of the atopic T cell response to the group 1 allergen of
      Cynodon dactylon (bermuda grass) pollen: pre- and post-allergen-specific
      immunotherapy.
AB  - BACKGROUND: Bermuda grass pollen (BGP) is an increasingly important seasonal
      aeroallergen in Australia and other subtropical and temperate regions. BGP shares
      minimal allergenic cross-reactivity with pollens of rye grass or other Pooideae
      grasses often used for desensitization regimens in grass pollen allergy. Current
      allergen immunotherapy is seldom used in asthmatic patients due to IgE-mediated
      side effects. Since clinically effective immunotherapy is linked with altered
      allergen-specific T cell response, characterisation of human T cell reactivity to
      Cyn d 1, the major B cell allergen of BGP, should permit the design of effective
      and safe immunotherapy for BGP allergy. METHODS: Short-term BGP-specific CD4+ T
      cell lines were established from peripheral blood of 14 BGP-sensitive patients
      before and after conventional 50% BGP and 50% 7-grass mix subcutaneous specific
      allergen immunotherapy (SIT). T cell diversity of antigen specificity and
      function was assessed by proliferation and cytokine production to BGP, Cyn d 1
      and Cyn d 1 peptides. RESULTS: Three highly immunogenic regions of Cyn d 1 were
      identified in 13/14 patients pre-SIT: Cyn d 1 (109-128), (181-209) and (217-241).
      The SIT regimen was clinically efficacious. Following SIT, decreased
      proliferation to BGP, Cyn d 1 and Cyn d 1 peptides was observed with a marked
      decrease in the IL-5:IFN-gamma ratio. CONCLUSIONS: Cyn d 1 is a major T cell
      allergen of BGP. Decreased Cyn d 1-specific IL-5 dominant T cell responses were
      observed in association with clinically effective treatment with the 50% BGP and
      50% 7-grass mix. Identified dominant T cell regions of Cyn d 1 should facilitate
      safer vaccine development for BGP-induced asthma in addition to rhinitis.

PMID- 11979050
TI  - A candidate vaccine against influenza virus intensively improved the
      immunogenicity of a neutralizing epitope.
AB  - BACKGROUND: The hemagglutinin (HA) of influenza viruses is one of the major
      targets of the humoral response. The role of serum antibody to HA in the
      protection against infection has been demonstrated by long-standing observation.
      In previous studies, we suggested that an epitope vaccine might be a new strategy
      against the virus. METHODS: HA sequences of 491 H3 subtype strains from the
      influenza sequence database were compared and analyzed. To acquire information on
      the immunogenicity of the F3 epitope, F3-epitope-specific antibody levels in 81
      patient sera infected with influenza virus were tested by ELISA. Based on the
      theory of the epitope vaccine, we designed an epitope peptide F3 (C
      KAYSNCYPYDVPDY-G-KAYSNCYPYDVPDY), which contains the repeated F3 epitope
      KAYSNCYPYDVPDY (aa92-105) on HA (H3N2). The specificity and the titer of the
      antibodies induced by the epitope vaccine were determined by ELISA. The
      neutralizing activities of these anti-F3 antibodies were shown by inhibiting
      influenza virus infection of MDCK cells. RESULTS AND CONCLUSION: Comparison of HA
      sequences of 491 H3 subtype strains indicates that this epitope is highly
      conservative. Analysis of the sera from influenza virus-infected patients
      revealed a very low level of F3 epitope-specific antibodies, suggesting the poor
      immunogenicity of the F3 epitope on influenza virus. The epitope vaccine based on
      the F3 epitope induced high levels of F3 epitope-specific antibodies recognizing
      the epitope peptide F3 (antibody titer in antisera up to 1:25,600). Besides, the
      antisera could also recognize the natural HA in Western blotting. Interestingly,
      these antisera induced by the epitope vaccine could inhibit infection of MDCK
      cells by influenza virus (strain A/Wuhan/359/95) in the neutralization assay.
      These results suggest that the epitope vaccine can intensively increase the
      immunogenicity of neutralizing epitopes and may provide a new way to develop an
      effective vaccine against influenza virus.

PMID- 11979051
TI  - The hypothalamic melanocortin system stimulates the hypothalamo-pituitary-adrenal
      axis in vitro and in vivo in male rats.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH) is an agonist, and agouti
      related protein (Agrp) an endogenous antagonist at the melanocortin 3 and 4
      receptors which are found in the central nervous system (CNS). We have examined
      the effect of alpha-MSH and Agrp on the hypothalamo-pituitary-adrenal (HPA) axis
      in vitro and in vivo in male rats. Intraparaventricular nuclear (iPVN) injection
      of [Nle(4),D-Phe(7)]-alpha-MSH (NDP-MSH) (a long-acting alpha-MSH analogue)
      increased plasma adrenocorticotropic hormone (ACTH) (10 min post-injection: 25.0
      +/- 3.9 vs. saline 10.9 +/- 2.0, p < 0.05) and plasma corticosterone (10 min post
      injection: 174.1 +/- 14.2 vs. saline 124.7 +/- 16.3 ng/ml, p < 0.05). iPVN
      injection of Agrp(83-132) increased plasma ACTH (24.2 +/- 4.0 vs. saline 10.1 +/-
      1.0 pg/ml, p < 0.01). The combination of NDP-MSH and Agrp(83-132) administered
      iPVN significantly increased plasma ACTH (10 min post-injection: 21.3 +/- 3.8 vs.
      10.9 +/- 2.0, p < 0.05) and plasma corticosterone (10 min post-injection: 169.0
      +/- 15.1 vs. saline 124.7 +/- 16.3 ng/ml, p < 0.05), but there was no additive
      effect. Hypothalamic explants treated with alpha-MSH (100 nM) resulted in a 159
      +/- 23% increase in corticotropin-releasing hormone (CRH) release (p < 0.01) and
      175 +/- 12% increase in arginine vasopressin (AVP) release (p < 0.001) compared
      to basal. Agrp(83-132) (100 nM) administered to hypothalamic explants resulted in
      a 161 +/- 20% increase in CRH (p < 0.01) and 174 +/- 13% increase in AVP release
      (p < 0.001) compared to basal. Hypothalamic explants treated with the combination
      of alpha-MSH and Agrp(83-132) (100 nM) resulted in a 179 +/- 31% increase in CRH
      release (p < 0.01) and 130 +/- 9% increase in AVP release (p < 0.01) compared to
      basal, but there was no additive effect. This is the first report that both alpha
      MSH and Agrp(83-132) stimulate the HPA axis. The combination of alpha-MSH and
      Agrp(83-132) has no additive effect in vitro and in vivo in male rats. These
      results suggest that there may be another receptor independent of the known
      melanocortin receptors at which Agrp is acting.

PMID- 11979052
TI  - Forced swimming differentially affects male and female brain corticosteroid
      receptors.
AB  - Corticosteroid receptors are key mediators of the neuroendocrine response to
      stress. Previously, we have determined the effects of restraint stress on the
      regulation of corticosteroid receptor genes in the brain and pituitary of male
      and female rats. Significant gender- and regional-specific regulation of receptor
      mRNAs was observed. To further investigate the stressor specificity in the same
      context, we have determined glucocorticoid receptor (GR) and mineralocorticoid
      receptor (MR) mRNAs following exposure to swimming stress paradigms applied
      alone, or in combination with restraint stress. Our data revealed stressor
      specific alterations in GR or MR mRNA levels, which were more pronounced in
      males, the gender most affected by swimming stress. No alterations in GR or MR
      mRNA levels were detected in the female hippocampus and hypothalamus upon
      exposure to swimming paradigms, while in males the same stressors down-regulated
      GR mRNA in the hippocampus (chronic exposure) and up-regulated both genes in the
      hypothalamus (acute exposure). In the frontal cortex, acute swimming stress
      caused a reciprocal change in GR mRNA levels in the two sexes. The above
      difference is not due to circulating ovarian steroids, since ovariectomy did not
      change the female pattern of GR gene expression following acute stress. Our
      results further showed a hypothalamic-pituitary-adrenal axis facilitation to a
      novel superimposed stressor expressed at the level of limbic corticosteroid
      receptors: When chronically restrained rats of both sexes were exposed to acute
      swimming stress, a reduced GR/MR mRNA ratio, implying reduced feedback axis
      sensitivity, was detected in both the hippocampus and the hypothalamus. In
      conclusion, our work provides additional evidence on stressor, gender and region
      specificity in the regulation of brain corticosteroid receptors.

PMID- 11979053
TI  - Restraint stress modulates brain, pituitary and adrenal expression of angiotensin
      II AT(1A), AT(1B) and AT(2) receptors.
AB  - Angiotensin II (Ang II) AT(1) receptors are involved in the regulation of the
      stress response. In adult male rats, acute restraint increased AT(1A) mRNA in
      paraventricular nucleus. Repeated restraint increased AT(1A) mRNA and AT(1)
      binding in paraventricular nucleus and AT(1) binding in subfornical organ and
      median eminence. AT(1B) and AT(2) receptors were not expressed in brain areas
      involved in the stress response. Acute restraint increased anterior pituitary
      AT(1A) mRNA and AT(1) binding and decreased AT(1B) mRNA. During repeated
      restraint, the increase in AT(1A) mRNA in the anterior pituitary was maintained,
      but AT(1B) mRNA and AT(1) binding returned to normal levels. In adrenal zona
      glomerulosa, AT(1B) mRNA, AT(1) binding, AT(2) mRNA and AT(2) binding decreased
      during acute restraint. Receptor mRNA and binding returned to normal after
      repeated stress, with the exception of rebound increase in adrenal zona
      glomerulosa AT(2) mRNA. In adrenal medulla, AT(1A) mRNA increased and AT(2) mRNA
      decreased during acute restraint. AT(1A) mRNA remained increased during repeated
      restraint, while alterations in AT(2) mRNA were no longer present. Expression of
      AT(1A), AT(1B) and AT(2) receptors in the hypothalamic-pituitary-adrenal axis is
      tissue specific and is different in acute and repeated stress. Increased brain,
      pituitary and adrenomedullary AT(1A) receptor expression correlates with
      hypothalamic-pituitary-adrenal axis stimulation, supporting the hypothesis of Ang
      II, through selective AT(1A) receptor stimulation, as an important determinant of
      the acute and repeated stress response. Decreased adrenal zona glomerulosa and
      anterior pituitary AT(1B) receptors during acute stress can be interpreted as
      compensatory to increased stimulation by Ang II. There may be additional roles
      for adrenal AT(2) receptors during acute stress, possibly related to interaction
      or cross-talk with AT(1) receptors.

PMID- 11979054
TI  - Basal hypothalamo-pituitary-adrenal axis activity and corticotropin feedback in
      young and older men: relationships to magnetic resonance imaging-derived
      hippocampus and cingulate gyrus volumes.
AB  - Alterations in basal cortisol secretion and feedback sensitivity are reported in
      aging. However, it is not known whether these hypothalamus-pituitary-adrenal
      (HPA) axis alterations are related to structural brain changes. This study was
      designed to investigate these relationships in the human. Nine young (24.0 +/-
      1.2 years; mean +/- SE; range: 19-30) and 11 older (69.0 +/- 1.8 years; range: 59
      76) men, in addition to having standardized magnetic resonance imaging of their
      brains, were given 0.5 mg/kg cortisol or placebo intravenously in a double-blind,
      crossover study. As expected, older men had significantly smaller volumes for all
      brain regions. Although the groups did not differ in baseline HPA axis activity,
      there were significant and specific relationships between the brain volumes and
      the baseline measures of HPA activity. Namely, for young and older subjects
      combined and after controlling for age and cerebral vault size, hippocampal
      volumes were inversely associated with 24-hour urinary cortisol and basal
      corticotropin (ACTH) levels, and the anterior cingulate gyrus volume was
      negatively correlated with baseline ACTH. Elderly subjects had a slower decrease
      in ACTH levels (percent of baseline level) during the first 30 min after cortisol
      administration. However, no associations were observed between the ACTH feedback
      indices and any brain measure. This report, although based on a small number of
      subjects, supports previous studies showing a blunted ACTH fast feedback during
      normal aging. Hippocampal atrophy appears to be related to increased basal
      measures of HPA axis activity, but not to fast ACTH feedback. It remains possible
      that age-associated changes in fast feedback may be related to changes to other
      brain sites, such as hypothalamus or pituitary.

PMID- 11979055
TI  - Hypothalamic gene expression in sheep for cocaine- and amphetamine-regulated
      transcript, pro-opiomelanocortin, neuropeptide Y, agouti-related peptide and
      leptin receptor and responses to negative energy balance.
AB  - Hypothalamic pathways involved in the regulation of energy balance have not been
      widely studied in ruminants to date. Here, we used in situ hybridisation to study
      the gene expression of a number of leptin-sensitive receptors and neuropeptides
      in the ovine hypothalamus. Gene expression was first localised for cocaine- and
      amphetamine-regulated transcript (CART) and agouti-related peptide (AGRP). We
      then examined in adult male castrated sheep the effects of acute negative energy
      balance induced by a 4-day fast on the amounts of these mRNAs and those for
      leptin receptor (OB-Rb), neuropeptide Y (NPY) and pro-opiomelanocortin (POMC).
      CART mRNA was localised in the arcuate nucleus (ARC), paraventricular nucleus,
      median eminence and ventromedial hypothalamic nucleus, and extensive co
      localisation with POMC mRNA was demonstrated in the ARC. AGRP mRNA was localised
      in the ARC. Fasting up-regulated gene expression for OB-Rb and for the orexigenic
      neuropeptides NPY and AGRP in the ARC. There was a trend towards down-regulation
      of gene expression for the anorexigenic neuropeptide CART and no effect on POMC
      in the ARC, although these results are inconclusive. The presence or absence of
      oestradiol-containing subcutaneous implants did not influence gene expression or
      the effects of fasting. The hypothalamic changes were consistent with responses
      to the observed reduction in circulation leptin and suggest that the peripheral
      feedback and central mechanisms for restoring the energy balance may be largely
      conserved across monogastric and ruminant species.

PMID- 11979056
TI  - Plasma leptin levels are pulsatile in adult rats: effects of gonadectomy.
AB  - Leptin, primarily secreted by adipocytes, is a peripheral hormonal signal
      involved in the hypothalamic integration of energy homeostasis. We report that
      plasma leptin levels fluctuated in a pulsatile fashion in gonad-intact adult
      female and male rats. Whereas in male rats leptin was secreted in the form of low
      amplitude, high-frequency pulses, in female rats high-amplitude pulses were
      secreted at only a slightly lower frequency. Consequently, plasma leptin
      concentrations were higher in female than in male rats. Gonadectomy decreased
      leptin secretion but the sexually dimorphic leptin pulsatility pattern persisted.
      These results show that there is a distinct female-type and male-type leptin
      pulsatility pattern and each is amenable to augmentation by gonadal steroids
      either involving mechanisms that impart leptin pulsatility patterns directly at
      the level of adipocytes and/or at hypothalamic target sites.

PMID- 11979057
TI  - Leptin immunoreactivity is localized to neurons in rat brain.
AB  - Leptin is secreted from adipocytes and is thought to enter the brain to regulate
      and coordinate metabolism, feeding behaviour, energy balance and reproduction. It
      is now clear that there are many additional sites of leptin production, including
      human placenta, ovary, stomach, skeletal muscle, mammary gland, pituitary gland
      and brain. In the present work, we employed double-label immunofluorescent
      histochemistry to establish the neuronal localization of leptin immunoreactivity
      (IR). To accomplish this, we used the neuron-specific marker NeuN to label cells
      in the arcuate nucleus (ARC), piriform cortex and hippocampus. In the supraoptic
      nucleus (SON) and paraventricular nucleus (PVN), we used antisera to oxytocin and
      vasopressin as neuronal markers. Double labelling revealed leptin IR in neurons
      of the ARC and piriform cortex. Leptin IR was confined to the nucleus and to
      distinct perinuclear sites. In contrast, neurons in the CA 2/CA 3 region of the
      hippocampus showed little nuclear staining. Leptin IR was clustered around the
      nucleus in these cells. Neurons of the dentate gyrus exhibited both nuclear and
      perinuclear localization of leptin IR. In the SON/PVN, most oxytocin- and
      vasopressin-IR neurons also contained leptin IR, often in perinuclear sites. In
      conclusion, the neuronal, perinuclear localization of leptin IR in rat brain
      corresponds closely to that of leptin receptor (OB-R) IR, which has also been
      detected intracellularly. Our observation of leptin IR associated with cell
      nuclei suggests the existence of an OB-R distinct from the well-described
      membrane forms.

PMID- 11979058
TI  - Effects of carbamazepine on dexamethasone suppression and sleep
      electroencephalography in borderline personality disorder.
AB  - The pathophysiology of borderline personality disorder (BPD) remains obscure, but
      there is mounting evidence of brain dysfunction without focal abnormality. The
      dexamethasone suppression test (DST) and sleep electroencephalography (sleep EEG)
      have been studied in BPD, but the findings seem to be related to a concomitant
      axis I diagnosis of major depression (MD) rather than to BPD itself. There is no
      effective treatment for BPD. Carbamazepine (CBZ) has shown contradictory results
      and in a previous study, our results were negative. In this study, we
      investigated the effects of CBZ versus placebo on the DST and sleep EEG in a
      sample of 20 BPD patients without concomitant MD. CBZ given at doses that are
      therapeutic for epilepsy and affective disorders may have an effect on the DST
      and sleep EEG in BPD. CBZ significantly increased the postdexamethasone plasma
      cortisol values. This did not parallel MD or an increase in the Hamilton
      depression rating scores. CBZ also increased slow wave sleep (SWS). The
      mechanisms by which CBZ increased postdexamethasone plasma cortisol levels and
      SWS in BPD are discussed.

PMID- 11979059
TI  - Increase in amino acids in the pons after sleep deprivation: a pilot study using
      proton magnetic resonance spectroscopy.
AB  - Total sleep deprivation (TSD) is an efficient method to relieve depression. An
      involvement of GABAergic and glutamatergic neurotransmission in the
      pathophysiology of depression and the mechanism of action of TSD has been
      suggested. To directly assess the content of GABA, glutamate (Glu) and glutamine
      (Gln) before and after TSD, we estimated their concentrations in four brain
      regions in six healthy subjects using proton magnetic resonance spectroscopy. The
      unresolved estimate of GABA, Glu and Gln, as well as GABA and Gln were increased
      in the pons after 24 h of TSD, the effect being prominent in three subjects.
      There were no significant changes in the hypothalamus, thalamus or
      parietooccipital cortex. These preliminary data support earlier animal data and
      indirect findings in humans suggesting that GABA and Gln, especially in the
      pontine structures, may play a key role in the mechanism of TSD.

PMID- 11979060
TI  - Serum leptin and cholesterol values in suicide attempters.
AB  - The growing number of studies examining the relationship between suicide and
      lipid metabolism are based upon studies suggesting that cholesterol-lowering
      procedures may increase the risk of death due to suicide or impulsive-aggressive
      behavior. Leptin seems to be strongly associated with lipid metabolism. In the
      present study, serum total cholesterol and leptin levels were compared in 24
      suicide attempters and 24 healthy controls. The patients with suicide attempts
      had significantly lower serum cholesterol and leptin levels than controls. There
      was a positive correlation between cholesterol and leptin levels in both groups.
      Our results suggest that suicide attempts seem to be associated with decreased
      serum cholesterol and leptin levels.

PMID- 11979062
TI  - Association for serotonin transporter gene variable number tandem repeat
      polymorphism and schizophrenic disorders.
AB  - In contrast with two previous western reports, a recent study on a Chinese
      population found an association for allele 12 of the variable number tandem
      repeat (VNTR) in the second intron of the serotonin transporter (5-HTT) gene and
      schizophrenic disorders. We have replicated this finding for a Chinese population
      in Taiwan (114 schizophrenic patients and 127 controls), demonstrating a modest
      but significant statistical association for the 5-HTT-VNTR allele 12 and
      schizophrenic patients (one-sided p = 0.043). This positive finding further
      supports the proposition that the 5-HTT-VNTR allele 12 is a risk factor for
      schizophrenic disorders in Chinese populations, although the effect is weak.

PMID- 11979061
TI  - Dopamine D2 receptor and N-methyl-D-aspartate receptor 2B subunit genetic
      variants and intelligence.
AB  - The dopaminergic and glutamate systems have been implicated in cognitive
      function. We tested the associations between the dopamine D2 receptor (DRD2) and
      N-methyl-D-aspartate receptor 2B subunit (GRIN2B) gene variants and intelligence
      quotient (IQ). Subjects with the DRD2 A1/A1 genotype had a significantly higher
      mean performance IQ than A2/A2 carriers, while no significant differences in IQ
      scores were determined for the three GRIN2B genotype groups. These results
      suggest that genetic variants of the DRD2 gene may play a role in cognitive
      function. Considering the major role played by the dopaminergic system in general
      cognitive function, genetic variants of the dopamine receptors and those involved
      in metabolism and modulation of reuptake should be tested to improve gene-based
      prediction of general cognitive function.

PMID- 11979063
TI  - Plasma biopterin levels and depressive state in pregnancy and the early puerperal
      period.
AB  - Plasma total biopterin and tetrahydrobiopterin levels of 14 normal pregnant and
      15 normal puerperal women (within 1 week after delivery) were measured. In the
      first group, total biopterin levels were already increased (average: 18.2
      pmol/ml) in the second trimester and remained high until the early puerperal
      period. In the second trimester, the ratio of tetrahydrobiopterin to total
      biopterin levels decreased to 72.3% and even further to 66.1% in the third
      trimester. This tendency continued until the puerperal period. Compared with the
      control group (12 healthy nonpregnant women), total biopterin levels increased
      during pregnancy and the puerperal period (p < 0.001), and the ratio in the third
      trimester and the early puerperal period decreased (p < 0.001). The depressive
      state according to Zung's score appeared most markedly in the third trimester
      with a mean score of 48, and tended to recover to a mean score of 36.2 in the
      early puerperal period. In this period, a correlation was found between Zung's
      score and the total biopterin levels (r = 0.80), and the ratio of
      tetrahydrobiopterin levels to the total biopterin levels (r = -0.92). In the
      early puerperal period, total biopterin levels were higher in subjects with
      Zung's scores > or = 36 (p < 0.001); the ratios of this group were lower than
      those of subjects with Zung's scores <36 (p < 0.001). Plasma biopterin levels in
      pregnancy and the early puerperal period closely resembled those of patients with
      mood disorders who show depressive symptoms from a psychoneurological
      perspective. Therefore, it seems possible that a depressive state in pregnancy
      and the early puerperal period has the same pathology as depression.

PMID- 11979064
TI  - Effects of sertraline treatment on plasma cortisol, prolactin and thyroid
      hormones in female depressed patients.
AB  - The aim of the study was to evaluate the effects of 4 and 24 weeks of sertraline
      treatment (average dose 42.5 mg/day) on plasma hormone levels in 15 female
      patients with major depression. Baseline levels of triiodothyronine (T(3)) were
      lower, while cortisol, prolactin (PRL), thyroid-stimulating hormone (TSH), and
      thyroxin (T(4)) levels did not differ from the values in 16 female controls.
      There was a positive correlation between the scores on the Montgomery-Asperg
      Depression Rating Scale and baseline cortisol levels. Treatment with sertraline
      for 4 weeks increased plasma cortisol levels, while 24 weeks of sertraline
      treatment increased plasma T(3) levels in depressed patients. Neither 4, nor 24
      weeks of sertraline treatment affected PRL, T(4) and TSH levels in depressed
      patients. The data show different and time-dependent effects of sertraline
      treatment on plasma cortisol, PRL and thyroid hormones in female depressed
      patients.

PMID- 11979065
TI  - Concomitant endocrine and immune alterations during alcohol intoxication and
      acute withdrawal in alcohol-dependent subjects.
AB  - Although both alcohol intoxication and withdrawal have been demonstrated to
      produce significant endocrine alterations, no data exist on the effects of acute
      withdrawal on immune functions. Therefore, the current study investigated the
      effect of alcohol intoxication and acute withdrawal on plasma cortisol, prolactin
      and catecholamines, and blood leukocyte subset distribution in alcohol-dependent
      subjects. Nine male alcoholics admitted to the university clinic for alcohol
      dependence and 9 age-matched controls participated in the study. Blood was drawn
      from the alcohol-dependent subjects at 10:30 a.m. on day 0 (chronic alcohol
      intoxication), at the same time during acute alcohol withdrawal (day 1) and
      following the resolution of acute withdrawal (day 7). Blood was drawn from age-
      and gender-matched healthy control subjects at the corresponding time points.
      Plasma was then analyzed for hormone concentrations and blood examined for
      leukocyte subsets by flow cytometry. Alcohol-dependent patients displayed
      significantly elevated plasma cortisol during intoxication and withdrawal, which
      decreased to control levels following resolution of acute withdrawal. Small
      elevations of plasma prolactin and catecholamines were also observed during
      intoxication. Furthermore, alcohol-dependent subjects showed reduced absolute
      numbers of CD4(+) and CD8(+) T cells and natural killer cells compared with
      healthy controls across all time points. In contrast, although monocyte numbers
      were lower in alcohol-dependent patients during intoxication, acute alcohol
      withdrawal increased the number of monocytes in patients. Thus, alcohol
      dependence produces a general suppression of leukocyte subset populations in
      blood. However, resolution of acute alcohol withdrawal is associated with a
      return of plasma cortisol to control levels, and a concomitant increase in
      peripheral blood monocyte numbers.

PMID- 11979066
TI  - Seed finding in golden hamsters: a potential animal model for screening
      anxiolytic drugs.
AB  - Fasting hamsters overnight, followed by temporary isolation in a novel
      environment are stressful conditions that hamper their ability or motivation to
      find hidden sunflower seeds when returned to their home environment. Studies were
      done to test whether treatment with antianxiety drugs would reduce stress and
      shorten the latency to find the hidden seeds. Prior to testing, the animals were
      fasted for 18-20 h. Ninety minutes after intraperitoneal injection of test drugs
      (fluoxetine, buspirone, chlordiazepoxide, clozapine, desipramine, yohimbine), the
      animals were taken from their home cage and placed into a novel holding cage for
      2 min. During their absence, 6 sunflower seeds were buried under the bedding in
      one corner of their home cage. The animals were placed back into their home cage
      and timed for their latency to find the seeds in a 5-min observation period.
      Treatment with anxiolytics caused a dose-dependent reduction in the latency to
      find the sunflower seed, while treatment with other psychotherapeutics were
      ineffective. Seed finding is an extremely sensitive bioassay, responding to
      anxiolytics given in doses as low as 1 microg/kg. These data provide evidence
      that seed finding in hamsters may serve as an animal model for screening
      potential anxiolytic drugs.

PMID- 11979067
TI  - Effects of acute nicotine administration on cognitive event-related potentials in
      tacrine-treated and non-treated patients with Alzheimer's disease.
AB  - Earlier studies of cognitive event-related brain potentials (ERPs) reporting
      diminished amplitudes and delayed latencies of the P300 potential in dementia of
      the Alzheimer type (DAT), together with independent findings of the P300- and
      performance-enhancing properties of nicotine in normal adults, stimulated this
      study to explore the single-dose effects of nicotine on auditory and visual P300s
      in DAT. Thirteen patients, 6 currently receiving treatment with the
      cholinesterase inhibitor tacrine (tetrahydroaminoacridine; THA) and the remaining
      being medication free, were administered 2 mg of nicotine polacrilex under double
      blind, randomized, placebo-controlled conditions. Prior to nicotine
      administration, THA-treated patients exhibited shorter auditory P300 latencies
      than non-treated patients. Acutely administered nicotine failed to alter auditory
      P300, but increased the amplitudes of visual P300s in both DAT patient groups.
      Neither THA treatment nor single-dose nicotine altered behavioural performance in
      the visual and auditory task paradigms. The results are discussed in relation to
      nicotinic cholinergic, attentional and cognitive processes in DAT.

PMID- 11979068
TI  - Effects of caffeine on topographic quantitative EEG.
AB  - Despite the widespread use of caffeine as a central nervous stimulant, the
      central pharmacodynamic properties of the drug have not yet been conclusively
      evaluated in humans. The present study was undertaken to assess the acute effects
      of caffeine on measures of topographical quantitative electroencephalogram (EEG)
      in normal subjects. Ten healthy male volunteers (mean age +/- SD 25 +/- 4 years)
      received placebo and 200 mg of caffeine as powder with oral water solution
      (caffeine amount = 2 cups of coffee) under randomized, double-blind crossover
      conditions on two different occasions. Before administration and 30 min
      afterwards, a 17-channel quantitative EEG was recorded during relaxation with
      eyes open and closed (15 min each). Caffeine caused a significant reduction of
      total EEG power at fronto-parieto-occipital and central electrode positions of
      both hemispheres when the subjects kept their eyes open. Absolute power of the
      slow and fast alpha and slow beta activities was diminished in various regions of
      the brain (p < 0.05). The effect was more pronounced with the subjects keeping
      their eyes open than with eyes closed. It can be concluded that quantitative EEG
      is a sensitive method to assess the effects of psychostimulants on the human
      brain. Therefore, in pharmaco-EEG studies, environmental factors such as caffeine
      have to be excluded.

PMID- 11979069
TI  - Possible mechanisms of hypopigmentation in lichen sclerosus.
AB  - Lichen sclerosus (LS) shares with vitiligo a milky-white appearance. By biopsy,
      pathognomonic dermal sclerosis readily distinguishes LS from vitiligo and other
      causes of leukoderma. To determine what the mechanism of hypopigmentation is in
      LS, we examined samples from LS cases for alterations in melanin content (Fontana
      Masson stain) and melanocyte number (HMB-45 [PMEL-17/gp100], Mel-5 [TRP-1], Mart
      1 [Melan A]) and compared these findings with those in controls of normal skin,
      acute scars, vitiligo, and lichen planus (LP; a common inflammatory cause of
      hyperpigmentation). The degree and extent of melanization found in LS overlapped
      with that in acute scars showing predominantly hypomelanized keratinocytes, with
      that in LP containing regions with numerous melanophages, and with that in
      vitiligo exhibiting focal regions of keratinocytes devoid of melanin pigment. By
      hematoxylin-eosin staining and immunocytochemistry for Mel-5 and Mart-1, LS had a
      lower mean count of melanocytes than acute scars, LP, and normal skin per 200
      basal keratinocytes. In addition, a few LS cases had a significant loss of
      melanocytes comparable to that of vitiligo. Surprisingly, Mart-1 identified rare
      melanocytes in 67% of vitiligo cases and a significantly larger pool of
      melanocytes in LS and controls other than those labeled by Mel-5. Furthermore, LP
      and evolving lesions of LS contained the highest Mart-1 counts. HMB-45
      immunoreactive melanocytes were found in the majority of acute scars and in LP
      and late-stage LS lesions at significantly lower levels than Mel-5- and Mart-1-
      labeled melanocytes, but they were not found in vitiligo or normal skin. We
      propose that several mechanisms may play a role in the production of leucoderma
      in LS: 1) decreased melanin production; 2) block in transfer of melanosomes to
      keratinocytes; and 3) melanocyte loss. The latter finding may be the pathogenic
      connection (lichenoid dermatitis of LS triggering an autoimmune reaction to
      melanocytes) that underlies the documented association of LS with vitiligo.

PMID- 11979070
TI  - Relationship of tumorigenic malignant melanomas to dermal elastin: an expression
      of tumor/stromal interaction that may be related to prognosis.
AB  - Malignant melanomas, which produce a large number of substances active in
      connective tissue modulation, must contend with the dermis to grow and propagate.
      We studied the morphologic interactions between tumorigenic malignant melanomas
      and dermal elastin. Formalin-fixed and paraffin-embedded tissues of 108
      tumorigenic malignant melanomas were stained for elastic tissue with the Verhoeff
      van Gieson method. Various aspects of the relationship between malignant melanoma
      and dermal elastin were analyzed in relation to the histologic and clinical data
      using univariate and multivariate analyses. Tumor thickness, mitotic rate, and
      the presence of elastin remnants within the tumors were found to be independent
      negative prognostic factors, the latter with borderline significance. Tumors with
      more remnants of elastin were associated with higher stage of disease and lymph
      node and distant metastases. Tumor infiltration between the elastic fibers in the
      tumor depth was associated with high Clark level, greater tumor thickness, high
      stage of disease, and lymph node metastases. At least partial preservation of
      elastic fibers in the tumor depth was a relatively good prognostic factor whereas
      complete absence of elastin was an adverse factor. Focal or multifocal absence of
      elastin in the midst of the tumors or in their depth was usually associated with
      lymphocytic infiltrates. We suggest that tumors with remnants of elastic fibers
      and/or invasion between elastic fibers in their depth may be fast growing and
      highly invasive. The absence of elastin within tumors and at their advancing edge
      may be related to the elaboration of elastin-degrading substances by melanoma
      cells or various inflammatory cells. Our findings indicate that the relationship
      between malignant melanomas and dermal connective tissue components, specifically
      elastin, may have prognostic significance.

PMID- 11979072
TI  - How specific is the TUNEL reaction? An account of a histochemical study on human
      skin.
AB  - The TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)
      technique has been described as sensitive method of labeling apoptotic nuclei in
      tissues, which preferentially stains apoptotic strand breaks. In the current
      study, three commercially available TUNEL kits for paraffin-embedded and cryostat
      tissues were tested to optimize this method for the studies on human skin. The
      investigation included normal skin (n = 10), atopic eczema (n = 4), basal cell
      carcinoma (n = 5), and lupus erythematosus (LE) (n = 31) sections. Additionally,
      the expression of certain apoptotic markers (Fas antigen and Bcl-2 protein) was
      studied immunohistologically on normal and LE skin. During TUNEL labeling
      according to the manufacturers' protocols, abnormally high background and
      nonspecific staining were found in all skin sections. The manipulation with the
      pretreatment time and, in particular, the introduction of an additional step
      (terminating the labeling reaction by inhibiting the terminal deoxynucleotidyl
      transferase activity) in two kits led to a remarkable improvement in their
      performance. The conclusions are that it is generally difficult to establish a
      functionally specific TUNEL technique for skin sections and that the choice of a
      kit is absolutely crucial for obtaining reliable results. Considering the extent
      to which the apoptosis research has been carried out recently, it is advisable to
      remain critical in evaluating the results. Further, it is necessary to combine
      the TUNEL technique with the investigation of other apoptotic markers.

PMID- 11979071
TI  - Anetoderma: an altered balance between metalloproteinases and tissue inhibitors
      of metalloproteinases.
AB  - The amount of elastic fibers from lesional and healthy skin areas of five
      patients with anetoderma was determined by automated image analysis. Dermal
      elastic fibers were almost completely absent in anetodermic skin and preelastic
      fibers were undetectable or extremely rare. Organ cultures were performed using
      explants from affected and unaffected skin areas of the same patient. We
      identified and quantified proteases in the culture media of explants: MMP-1
      (collagenase 1), MMP-2 and MMP-9 (gelatinases A and B), MMP-3 (stromelysin 1),
      MMP-7 (matrilysin 1), and tissue inhibitors of metalloproteinases, TIMP-1 and
      TIMP-2. The data were compared with those of two healthy donors. For the five
      samples of anetodermic skin, MMP-1 levels were significantly higher compared with
      the uninvolved cultures and the two healthy samples. A significant increase of
      TIMP-1 expression was also observed in the affected cultures. We demonstrated a
      significant increase in the production of gelatinase A in lesional skin when
      compared with nonlesional skin and healthy donor samples. We found no significant
      production of TIMP-2 in the five samples of anetodermic skin compared with the
      samples from the two healthy donors. There was a significant decrease in TIMP-2
      expression in the five nonlesional samples compared with the control samples.
      These data are in favor of an altered balance in anetodermic patients between MMP
      2 and TIMP-2. Levels of MMP-9, MMP-3, and MMP-7 were significantly higher in the
      culture-conditioned media of the anetodermic skin samples than the nonlesional
      skin cultures. Because MMP-3, MMP-7, MMP-9 are known to degrade elastin, and MMP
      3 can activate the latent forms of MMP-7 and MMP-9, we propose that these
      metalloproteinases also participate in the degradation of elastic fibers in
      anetodermic skin.

PMID- 11979073
TI  - Human papillomavirus-negative spindle cell carcinoma of the vulva associated with
      lichen sclerosus: case report and literature review.
AB  - Although spindle cell carcinoma (SC) is a common neoplasm in the oral cavity,
      upper respiratory tract, and other head and neck areas, its occurrence in the
      vulva is rare. We report a case of this rare condition with immunohistochemical,
      ultrastructural, and human papillomavirus (HPV) testing. The neoplastic cells
      were positive for vimentin, keratins (AE1-AE3, keratin 902, and keratin 903), and
      epithelial membrane antigen. Ultrastructurally, they showed primitive junctions
      and tonofilaments. HPV testing by polymerase chain reaction was negative. In
      addition, we review the clinicopathologic findings of the four well-documented
      cases of vulvar SC that have been reported previously in the English language
      literature.

PMID- 11979074
TI  - Pilomatrix carcinoma with lymph node and pulmonary metastasis: report of a case
      arising on the knee.
AB  - A 58-year-old woman presented with a pilomatrix carcinoma on the right knee. The
      tumor developed at the site of a previous lesion that had been present since she
      was 30 years old. Histologic study showed the presence of basaloid cells with
      numerous atypical mitoses, shadow cells, and calcification. After several
      surgical excisions, the tumor mass infiltrated the subcutaneous tissue, muscle,
      and bone, resulting in inguinal lymph node and pulmonary metastasis. We also
      review the literature and comment on the histopathologic differences from other
      cutaneous tumors.

PMID- 11979075
TI  - Disseminated porokeratosis with fatal metastatic squamous cell carcinoma: an
      additional case of "malignant disseminated porokeratosis".
AB  - We report on a patient with a disseminated form of porokeratosis in whom bowenoid
      lesions and squamous cell carcinoma developed in an apparent sequential
      progression. Local and disseminated metastases ensued, resulting in the death of
      the patient. Furthermore, we found an overexpression of the p53 protein in the
      keratinocytes beneath and adjacent to the cornoid lamella in the porokeratotic
      lesion and throughout the epidermis in a bowenoid lesion. Although malignancy has
      been reported previously in various types of porokeratosis, the development of
      fatal metastatic squamous cell carcinoma in the setting of this disease is a rare
      event. The histopathologic findings of this case document the association of
      porokeratotic lesions with bowenoid dysplasia and aggressive squamous cell
      carcinoma and confirm that a p53 functional aberration can be important in a
      malignant outcome such as this.

PMID- 11979077
TI  - The man behind the eponym. George Crichton Wells: eosinophilic cellulitis (Wells
      syndrome).

PMID- 11979076
TI  - Tricholemmal carcinoma in continuity with trichoblastoma within nevus sebaceus.
AB  - A nodule arising within the nevus sebaceus on the vertex of the scalp of a 68
      year-old woman was histopathologically and immunohistochemically investigated. We
      also used immunohistochemistry to investigate the cytokeratin (CK) distribution
      of the outer root sheaths of normal terminal hair follicles. The nodule consisted
      of two parts, a main exophytic part with a lobular proliferation and a small
      peripheral part with the features of trichoblastoma. The main exophytic lesion
      consisted of lobular aggregations composed of both or either basaloid cells and
      clear cells with the silhouette and cytology of malignancy. The columnar clear
      cells were aligned in a palisade at the periphery of the aggregations of clear
      cells, and the aggregations located in the superficial dermis were connected to
      the follicular infundibular structures. Almost all of the neoplastic aggregations
      were diffusely positive for CK7 (OV/TLR/30), and the innermost or inner cells of
      the neoplastic aggregations were positive for CK17; a similar staining pattern to
      that in the lower portion of the outer root sheath between the A and B fringes in
      normal terminal hair follicles. The exophytic part of the lesion was a malignant
      neoplasm with differentiation mainly toward the lower segment of the outer sheath
      between the A and B fringes of the terminal hair follicle, namely tricholemmal
      carcinoma. Our case may represent a collision of two distinctive neoplasms
      (tricholemmal carcinoma and trichoblastoma), however, an intimate relationship
      between these two neoplasms also should be considered.

PMID- 11979078
TI  - Can we understand keratoacanthoma?

PMID- 11979083
TI  - Pseudoinfiltration: an underrecognized feature in melanocytic lesions.

PMID- 11979084
TI  - Desmoplastic Spitz nevus showing vascular proliferation more prominently in the
      deep portion.

PMID- 11979085
TI  - Malignant Sertoli cell tumors of the testis: a study of 13 examples of a neoplasm
      frequently misinterpreted as seminoma.
AB  - The distinction of Sertoli cell tumors from seminoma is critical to ensure proper
      treatment. Although usually straightforward, we highlight herein 13 malignant
      Sertoli cell tumors of the testis with light microscopic features that mimicked
      seminoma. All of the cases were received in consultation, 10 with submitting
      diagnoses of seminoma, usually of classic type, but three cases of spermatocytic
      type. Patients ranged from 15 to 80 years of age (median 37 years); all presented
      with testicular masses. The tumors were typically firm, white to yellow-tan, and
      often had foci of hemorrhage. The dominant microscopic pattern was nested or
      sheet-like, with some tumors having secondary patterns of trabeculae-solid
      tubules, hollow tubules, and pseudofollicles. Tumor cells were polygonal with
      conspicuous clear cytoplasm in 12 cases; the cytoplasm was focally eosinophilic
      in 10 cases, but this was never conspicuous. Nine tumors had cytoplasmic
      vacuoles, and three of four that were investigated stained for intracytoplasmic
      glycogen. Nuclei were small (5) to medium-sized (8), round-to-oval (13), and
      vesicular with irregular contours (11). Nucleoli were present in 11 tumors (six
      small; five large). Stromal fibrosis (12) and lymphoid infiltrates (10) were
      conspicuous, and tumor necrosis (11) and vascular invasion (8) also were seen.
      Mitotic figures ranged from <1 to 21/10 high power fields (HPF) (median 1/10
      HPF). Staining for inhibin-alpha, epithelial membrane antigen, and cytokeratin
      (AE1/AE3) was positive in four of four, six of six, and three of six cases,
      respectively; placental alkaline phosphatase was negative in all five tumors
      investigated. The nested growth pattern, prominence of clear cells, lymphoid
      infiltrate, inconspicuous tubular differentiation, cytoplasmic glycogen, and
      prominent nucleoli caused these tumors to be mistaken for seminomas. The smaller,
      less pleomorphic nuclei of Sertoli cell tumors, their lower mitotic rate, and the
      absence of intratubular germ cell neoplasia are helpful differential features.
      Immunohistochemistry is a useful adjunct in confirming the diagnosis of Sertoli
      cell tumor, but only if the overlapping features are appreciated by conventional
      microscopy and the diagnosis of Sertoli cell tumor included in the differential.

PMID- 11979086
TI  - Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from
      malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases.
AB  - No comprehensive series has evaluated the histologic features of pheochromocytoma
      to separate benign from malignant pheochromocytoma by histomorphologic parameters
      only. Fifty histologically malignant and 50 histologically benign
      pheochromocytomas of the adrenal gland were retrieved from the files of the Armed
      Forces Institute of Pathology. The patients included 43 females and 57 males,
      with an age range of 3-81 years (mean 46.7 years). Patients usually experienced
      hypertension (n = 79 patients). The mean tumor size was 7.2 cm (weight was 222
      g). Histologically, the cases of malignant pheochromocytomas of the adrenal gland
      more frequently demonstrated invasion (vascular [score = 1], capsular [score =
      1], periadrenal adipose tissue [score = 2]), large nests or diffuse growth (score
      = 2), focal or confluent necrosis (score = 2), high cellularity (score = 2),
      tumor cell spindling (score = 2), cellular monotony (score = 2), increased
      mitotic figures (>3/10 high power fields; score = 2), atypical mitotic figures
      (score = 2), profound nuclear pleomorphism (score = 1), and hyperchromasia (score
      = 1) than the benign tumors. A Pheochromocytoma of the Adrenal gland Scaled Score
      (PASS) weighted for these specific histologic features can be used to separate
      tumors with a potential for a biologically aggressive behavior (PASS > or =4)
      from tumors that behave in a benign fashion (PASS <4). The pathologic features
      that are incorporated into the PASS correctly identified tumors with a more
      aggressive biologic behavior. Application of these criteria to a large cohort of
      cases will help to elucidate the accuracy of this grading system in clinical
      practice.

PMID- 11979087
TI  - Endometrial stromal nodules and endometrial stromal tumors with limited
      infiltration: a clinicopathologic study of 50 cases.
AB  - Experience with endometrial stromal nodules (ESNs) is limited, and no series has
      been published since the frequent misdiagnosis of highly cellular leiomyomas as
      ESNs was highlighted. Additionally, although the entirely well-circumscribed
      margin of most ESNs readily allows a separation from endometrial stromal sarcomas
      with their typical permeative invasion, some tumors have greater irregularity of
      their margin than allowable for an ESN following the guidelines of Tavassoli and
      Norris, but without the typical, and usually extensive, infiltration of
      endometrial stromal sarcomas. These have been diagnosed by us descriptively as
      endometrial stromal tumors with limited infiltration. Three cases of this type
      and 47 ESNs that occurred in patients from 31 to 86 years (mean 53 years) were
      analyzed. The tumors were typically fleshy and at least in part yellow and ranged
      from 1.2 to 22 cm (mean 7.1 cm). Seven tumors had one to six focal margin
      irregularities; in four tumors these did not extend >3 mm beyond the main border
      of the tumor and were up to three in number. The other three (endometrial stromal
      tumors with limited infiltration) had four to six irregularities extending up to
      9 mm beyond the main border of the tumor. Most neoplasms were densely cellular,
      but nine were hypocellular with areas that were fibrous, hyalinized, myxoid,
      edematous, or combinations thereof. The tumor cells almost always had scant
      cytoplasm, but in one tumor many cells had abundant eosinophilic cytoplasm. There
      was minimal cytologic atypia. Forty-four tumors had mitotic rates of up to 5 per
      10 high power fields, but six had higher rates. Typical arterioles, some of which
      had hyalinized walls in nine cases, were numerous in all 50 tumors but were
      conspicuous on low-power examination in only 22. Larger, sometimes thick-walled
      vessels were seen in 37 tumors but were much less conspicuous than in highly
      cellular leiomyomas and were often present near the margin of the tumor. The
      cleft-like spaces of highly cellular leiomyomas were not a feature of these
      tumors. Twenty-three tumors showed variable degrees of smooth muscle
      differentiation and sex cord-like differentiation occurred in 12. Cysts were
      present in 17 tumors and infarct-type necrosis in 34, the latter sometimes
      causing initial concern for a malignant neoplasm. Follow-up information,
      available for 32 patients, including five patients whose tumor had some margin
      irregularity, ranged up to 214 months (mean 43.5 months). All patients were alive
      with no recurrence. Follow-up information was unfortunately not available for the
      two tumors with the greatest degree of infiltration. The major conclusions of our
      study are as follows: ESNs are characteristically soft and yellow; thorough
      sampling of their margin is mandatory; smooth muscle metaplasia is common and
      irregular interdigitation of stromal neoplasia with metaplastic smooth muscle may
      erroneously suggest myometrial infiltration; although typically densely cellular
      about 20% of ESNs are hypocellular and often fibrous; cellular neoplasms are
      often punctuated by hyaline plaques; sex cord-like differentiation, broad zones
      of necrosis and rarely epithelioid cells may complicate the microscopic
      appearance; typical arterioles are an important microscopic finding but are not
      always striking, particularly on low-power evaluation; the tumors may have a
      component of large blood vessels more typical of highly cellular leiomyomas, but
      they are not as conspicuous as in the latter and the clefts that are frequent in
      highly cellular leiomyomas are not a feature of ESNs.

PMID- 11979088
TI  - A rosette-forming glioneuronal tumor of the fourth ventricle: infratentorial form
      of dysembryoplastic neuroepithelial tumor?
AB  - Eleven cases of a distinctive tumor of the posterior fossa are described. The
      patients (age range 12-59 years) presented with headache and/or ataxia.
      Neuroimaging revealed a relatively discrete, focally enhancing mass(es) primarily
      involving the aqueduct, fourth ventricle, and cerebellar vermis. Hydrocephalus
      was present in seven cases, and two lesions were multicentric. In two cases a
      significant increase in tumor size was documented. Gross total or subtotal
      resections were achieved in 10 cases. One patient underwent biopsy alone and
      another received postoperative irradiation. Histologically, two components were
      identified in all cases. One consisted of neurocytes forming neurocytic and/or
      perivascular pseudorosettes in a fibrillary, partly microcystic matrix. The
      second, astrocytic component resembled pilocytic astrocytoma in 10 cases and
      consisted of fibrillated spindle cells with oval nuclei associated with
      occasional Rosenthal fibers, granular bodies, glomeruloid capillaries, and
      microcalcifications. Regionally, this component was more diffuse and patternless,
      consisting of sheets of round to oval, oligodendrocyte-like cells. Rare ganglion
      cells were seen in four cases. The rosettes were consistently synaptophysin and
      MAP-2 immunoreactive, whereas the spindle cells were positive for S-100 protein
      and glial fibrillary acidic protein. Overall, atypia was minimal; no mitoses were
      found, and Ki67 labeling indices were low. Ultrastructurally, the neurocytic
      cells featured processes containing microtubules and occasional dense core
      granules. Mature synapses were found in one of the four cases studied. Although
      the histologic features of this unique tumor superficially resemble those of
      dysembryoplastic neuroepithelial tumor, rosette formation by neuronal cells, the
      frequent presence of a pilocytic astrocytoma component, and the growing nature of
      the lesion argue against that diagnosis, as does occasional multifocality.

PMID- 11979089
TI  - A comparative analysis of 57 serous borderline tumors with and without a
      noninvasive micropapillary component.
AB  - The literature concerning serous borderline tumors with a noninvasive
      micropapillary component suggests an association with invasive implants. We
      compared the clinicopathologic features of micropapillary serous borderline
      tumors (MSBTs) with typical SBTs to determine the following: 1) the importance of
      focal micropapillary architecture in an otherwise typical SBT, 2) the behavior of
      low-stage MSBTs, 3) whether high-stage MSBTs are inherently more aggressive than
      high-stage SBTs, and 4) whether invasive implants are prevalent in an MSBT cohort
      without referral selection bias. The 57 borderline tumors studied were diagnosed
      at a university hospital between 1981 and 1998; they included 14 MSBTs, 35 SBTs,
      and 8 SBTs with focal micropapillary features. None of the specimens were
      referrals for expert pathologic consultation, thus distinguishing our study group
      from most of those previously reported. Neither MSBTs nor SBTs were associated
      with invasive implants at diagnosis (0 of 14 and 0 of 43, respectively). They
      also did not differ with respect to overall stage at diagnosis, but MSBTs were
      more frequently bilateral than SBTs (71% versus 23%, p = 0.001). There was an
      increased risk of recurrence in MSBT versus SBT (3 of 14 versus 1 of 43, p =
      0.035), but this was stage related; there was no difference between groups when
      evaluating recurrence in stage I disease (0 of 8 versus 0 of 27). There was no
      difference in recurrence or stage at diagnosis between SBTs with focal
      micropapillary features and other SBTs. There was 100% survival in all groups. We
      conclude that high-stage MSBTs with noninvasive implants should be considered a
      subtype of SBTs with an increased risk of recurrence. Stage I MSBTs demonstrate
      clinical features that are similar to low-stage SBTs. Focal micropapillary
      architecture (<5 mm) has no bearing on outcome. MSBTs in the general population
      are not strongly associated with invasive implants.

PMID- 11979090
TI  - Pleomorphic liposarcoma: clinicopathologic, immunohistochemical, and follow-up
      analysis of 63 cases: a study from the French Federation of Cancer Centers
      Sarcoma Group.
AB  - The clinicopathologic and immunohistochemical features of 63 pleomorphic
      liposarcomas are presented. There were 35 men and 28 women (median age 63 years;
      range 18-93 years). Tumor size ranged from 2 to 23 cm (median 10 cm). Tumor
      locations included lower extremity (36.5%), especially the thigh (28.5%), limb
      girdles (17.5%), upper extremity (16%), thoracoabdominal wall (9.5%), and
      internal trunk (20.5%). A total of 75% were deep seated and/or
      extracompartmental. Histologically, lesions show a varying combination of
      lipogenic and nonlipogenic areas characterized by malignant fibrous histiocytoma
      like, round cell liposarcoma-like, and/or epithelioid/carcinoma-like features. A
      pericytic pattern was focally present in 15 (24%) tumors. Eighteen (29%) lesions
      were grade 2, and 45 (71%) were grade 3 sarcomas. Tumor necrosis was observed in
      51 (81%) cases, vascular invasion in three, and mitotic counts ranged from 3 to
      124 per 10 high power fields (median 25). Lipogenic areas were S-100 protein
      immunoreactive, at least focally, in 20 of 42 (48%) cases. Nonlipogenic areas
      showed focal reactivity for smooth muscle actin (24 of 49; 49%), desmin (9 of 48;
      19%), CD34 (18 of 45; 40%), S-100 protein (5 of 49, 10%), CD68 (6 of 46, 13%),
      and epithelial membrane antigen (13 of 49, 26.5%). Epithelioid areas showed
      epithelial membrane antigen (4 of 11; 36%) but not cytokeratin (0 of 11)
      reactivity. Treatment procedures in 51 patients consisted of simple tumorectomy
      (16) and wide excision (33). Five and 31 patients received neoadjuvant and
      adjuvant chemotherapy and/or radiation therapy, respectively. Follow-up (48
      patients, range 7-276 months; median 38 months) showed a 45% local recurrence
      rate and a 42.5% metastasis rate, metastases occurring mostly in lungs and
      pleura. Seventeen patients (35%) died of disease, of whom none was metastatic at
      diagnosis. Five-year overall, metastasis-free, and local recurrence-free
      survivals were 57%, 50%, and 48%, respectively. Patient age > or =60 years,
      truncal tumor location, deep situation, tumor size >5 cm, vascular invasion, and
      incomplete tumor excision were significant adverse prognostic factors. Tumor
      grade and histology did not affect patient outcome. In conclusion, pleomorphic
      liposarcoma is a rare, often deep-seated and limb-based aggressive and
      metastasizing neoplasm of late adulthood. It shows a wide range of morphologic
      appearances, but tumor grade and histology have no effect on patient outcome.

PMID- 11979091
TI  - The ectopic expression of gastric mucin in extramammary and mammary Paget's
      disease.
AB  - The immunohistochemical analysis of the ectopic expression of gastric mucin has
      been used as a valuable tool for the identification of several neoplasms. We
      performed an immunohistochemical examination of the expression of gastric,
      intestinal, and mammary-type mucins in 25 lesions from patients with extramammary
      Paget's disease (ExMPD) and in 10 lesions from patients with mammary Paget's
      disease (MPD). All ExMPD lesions were immunopositive for HGM-45, a marker of
      gastric surface mucous cells, whereas only 40% of MPD lesions were weakly
      immunopositive. No markers for gastric-gland mucous cells were found in almost
      all ExMPD and MPD lesions, and markers for intestinal mucin were recognized in
      only a few lesions. Antibodies specific for MUC1, a marker of mammary-type mucin,
      gave positive results in both ExMPD and MPD lesions at a higher frequency than
      antibodies specific for gross cystic disease fluid protein-15. Our analysis
      indicates that Paget's cells contain gastric surface-type mucin in ExMPD and they
      contain mammary-type mucin in both ExMPD and MPD. The ectopic localization of
      mucosubstances may be a further step in the understanding of these lesions.
      Moreover, antibodies against MUC1 seem to be a useful tool for the diagnosis of
      both ExMPD and MPD.

PMID- 11979092
TI  - Immunophenotype does not correlate with lymph node histology in chronic
      lymphocytic leukemia/small lymphocytic lymphoma.
AB  - The presence of prominent proliferation centers (PCs) in lymph nodes (LNs)
      involved with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
      has been associated with atypical blood smear morphology. Atypical CLL has in
      turn been associated with variant immunophenotypes and poor outcome. However, the
      significance of abundant PCs remains controversial. We have analyzed the flow
      cytometric immunophenotypic features of 54 CLL/SLL LNs and correlated these
      findings with the morphologic and clinical features. The LN histology was
      assigned to one of two groups based on the prominence of PCs: Group I LNs
      contained scattered small, sometimes ill-defined PCs in a background of
      monotonous small round lymphocytes. Group II LNs had increased numbers and sizes
      of PCs resulting in an obviously nodular appearance at low magnification. Flow
      cytometry was performed using broad three- or four-color antibody panels that
      included anti-CD5, CD19, CD20, CD23, CD38, FMC7, and surface immunoglobulin
      (sIg). The intensity of expression of all markers was scored semi-quantitatively
      using isotypic controls and internal positive and negative populations as
      standards. There were 32 group I and 22 group II LNs that, by definition,
      expressed CD19, CD5, and CD23. Little variability was seen in the intensity of
      expression of CD19, and the majority of cases expressed CD23 brightly. CD5 varied
      from very dim to an intensity similar to that of normal T cells; the majority had
      an intermediate level of CD5 expression. FMC7 was expressed to a significant
      extent in 11 cases (21%). CD20 was relatively bright in 17 cases (32%). sIg was
      dim in 29 cases (55%) and moderate or bright in 24 cases (45%). CD38 was
      expressed significantly in 25 cases (47%). There was no correlation between
      histologic group and intensity of expression of any individual marker or with an
      immunophenotypic atypia score based on FMC7, CD20, and sIg. There was also no
      correlation between morphology or immunophenotype and clinical features. These
      findings do not support the interpretation that the prominence of proliferation
      centers in CLL/SLL LNs defines biologically distinct subtypes.

PMID- 11979093
TI  - Epstein-Barr virus-positive B-cell lymphoproliferative disorders arising in
      immunodeficient patients previously treated with fludarabine for low-grade B-cell
      neoplasms.
AB  - We describe five patients with treated low-grade B-cell neoplasms who
      subsequently developed Epstein-Barr virus (EBV)-positive B-cell
      lymphoproliferative disorders (BLPDs). The low-grade B-cell neoplasms were B-cell
      chronic lymphocytic leukemia in four patients and splenic marginal zone lymphoma
      in one patient. All patients had received treatment with fludarabine for the low
      grade B-cell neoplasm, and three had also received Campath-1H. The EBV-BLPDs
      arose 2-12 months after completion of fludarabine therapy and morphologically
      resembled the EBV-BLPDs that occur in the setting of iatrogenic immunodeficiency.
      Molecular genetic studies showed that these lesions were clonally distinct from
      the low-grade B-cell neoplasm in three of four cases assessed. Two patients did
      not receive therapy for the EBV-BLPD. The lesions regressed spontaneously in both
      patients but recurred in one. One patient underwent surgical excision and remains
      without evidence of the EBV-BLPD. One patient received aggressive multiagent
      chemotherapy with a complete response initially, but the EBV-BLPD recurred after
      12 months. One patient received antiviral therapy and responded completely but
      died 2 months later of an opportunistic infection. We conclude that patients with
      low-grade B-cell neoplasms treated with fludarabine, possibly in combination with
      other immune suppressive agents, may subsequently develop EBV-BLPDs that
      morphologically resemble other iatrogenic immunodeficiency-associated BLPDs. Most
      are clonally distinct from the underlying low-grade B-cell neoplasm. A subset of
      these lesions may regress without systemic therapy.

PMID- 11979094
TI  - Abnormal hepatic expression of fibrillin-1 in children with cholestasis.
AB  - Fibrillin-1, one of the main constituents of microfibrils, is present in normal
      adult liver and overexpressed in fibrotic area around cirrhotic nodules and
      hepatocellular carcinoma. In this work fibrillin-1 expression was studied by
      immunohistochemistry in liver samples from children with various cholestatic
      diseases corresponding to paucity of intrahepatic bile ducts, biliary atresia,
      congenital hepatic fibrosis, Byler's disease, mitochondrial cytopathy, sclerosing
      cholangitis, or choledochal cyst. As controls, histologically normal liver
      samples were used. In control liver, as in adult, fibrillin-1 was expressed in
      vessel walls, sinusoids, and portal connective tissue, particularly at the
      interface with the limiting hepatocytic plate and close to the basement membrane
      of bile ducts. In paucity of intrahepatic bile ducts without fibrosis, the
      fibrillin-1 distribution was similar to controls. In cholestatic diseases
      associated with severe fibrosis, such as biliary atresia, congenital hepatic
      fibrosis, Byler's disease, mitochondrial cytopathy, or sclerosing cholangitis, an
      enhanced deposition of fibrillin-1 was observed in portal connective tissue and
      fibrous septa. The strong fibrillin-1 expression close to the basement membrane
      of biliary structures was lost in cholestatic diseases, except biliary atresia.
      Finally, in normal and pathologic tissues, fibrillin-1 was co-localized with its
      putative receptor alphaVbeta3 in sinusoids but not around biliary structures.

PMID- 11979095
TI  - Respiratory bronchiolitis: a clinicopathologic study in current smokers, ex
      smokers, and never-smokers.
AB  - The clinical and pathologic features of 109 cases of respiratory bronchiolitis
      (RB) identified from review of 156 consecutive surgical lung biopsy specimens
      were studied. A total of 107 of the 109 cases (98%) occurred in smokers,
      including all 83 current smokers and 24 of 49 ex-smokers (49%). RB persisted in
      some patients for many years after stopping smoking, occurring in one third of
      patients 5 years after quitting, and in one patient 32 years afterwards. A
      correlation was found between degree of cytoplasmic pigmentation of macrophages
      and number of pack-years smoked and also between the presence of peribronchiolar
      fibrosis and number of pack-years. No correlation was found between pulmonary
      function test results and pathologic findings. A desquamative interstitial
      pneumonia-like reaction was observed in six individuals. One patient each with a
      desquamative interstitial pneumonia-like reaction and one with RB were diagnosed
      based on clinical findings with desquamative interstitial pneumonia and RB
      associated interstitial lung disease, respectively. No histologic features
      distinguished desquamative interstitial pneumonia from a desquamative
      interstitial pneumonia-like reaction or RB-associated interstitial lung disease
      from RB. Five cases of variant RB were encountered that resembled RB except that
      macrophage cytoplasm lacked pigment. All occurred in never-smokers, and their
      significance is unknown. RB is an accurate histologic marker of cigarette
      smoking, and it may be found many years after smoking ceases. There are no
      reliable histologic features to distinguish RB-associated interstitial lung
      disease from RB or desquamative interstitial pneumonia-like reactions from
      desquamative interstitial pneumonia.

PMID- 11979097
TI  - Hyaline vascular Castleman's disease with HMGIC rearrangement in follicular
      dendritic cells: molecular evidence of mesenchymal tumorigenesis.
AB  - Chromosomal aberrations involving chromosome segment 12q13-15 are a common
      finding in a variety of benign mesenchymal tumors. The target gene encodes for
      HMGIC, a member of the high mobility group protein family. These proteins act as
      architectural transcription factors. HMGIC plays a role as a common genetic
      denominator in benign mesenchymal tumorigenesis. We report a case of hyaline
      vascular Castleman's disease with intragenic HMGIC rearrangement, due to a clonal
      cytogenetic aberration involving the long arm of chromosome 12 [46,XX,
      add(1)(q21),der(6)t(6;12) (q23;q15),add(7)(p22), 
      9,inv(9)(p11q13),del(12)(q15),+mar] obtained after short-term primary cultures. A
      combined immunocytologic-cytogenetic approach enabled us to demonstrate the
      exclusive presence of HMGIC rearrangement in anti-CD21 reactive follicular
      dendric cells. This finding confirms that a clonal proliferation of follicular
      dendritic cells occurs in the hyaline vascular variant of Castleman's disease. It
      also provides a possible molecular pathway explaining stromal overgrowths and
      stromal neoplasms developing from this disorder.

PMID- 11979096
TI  - Persistent (recurrent) Spitz nevi: a histopathologic, immunohistochemical, and
      molecular pathologic study of 22 cases.
AB  - This report describes 22 Spitz nevi that seemed to have been clinically removed
      but persisted and clinically recurred at the biopsy site. These were evaluated in
      terms of histopathology, immunohistochemistry, and molecular pathology using
      comparative genomic hybridization (CGH) and fluorescent in situ hybridization.
      One of these 22 lesions was originally reported as an atypical melanocytic
      proliferation with some features of a Spitz nevus and was included in the study
      set at an early stage but was later recognized as melanoma after metastasis to
      regional lymph nodes 3 years after the local recurrence. We noted four
      histopathologic patterns in the recurrent lesions: 1) a predominantly
      intraepidermal pattern resembling "pseudomelanoma" as seen in recurrent "common"
      melanocytic nevi, 2) a compound, mostly nested pattern above or within a scar
      that was nearly identical to the originally biopsied Spitz nevus, 3) a nodular
      growth pattern that closely simulated invasive melanoma, and 4) a desmoplastic
      pattern resembling an intradermal desmoplastic Spitz nevus. Although the majority
      of recurrent lesions exhibited asymmetry and pagetoid spread, the dermal
      component usually had a low mitotic rate and retained architectural and cytologic
      maturation, which allowed distinction from invasive melanoma. Except for the
      metastasizing melanoma, the immunostaining pattern with S-100 and HMB-45 was
      identical to that previously reported for Spitz nevi. Ki67 revealed a very low
      proliferation rate in all cases, including the melanoma. CGH performed in 10
      cases yielded results consistent with Spitz nevi in eight cases. The remaining
      two cases showed CGH profiles more typical of melanoma, and one of these was the
      above-referenced case of melanoma, proven by metastasis. Although ancillary
      molecular techniques such as CGH are of great help in distinguishing these from
      melanoma, until such techniques become widely available we advocate complete but
      conservative excision of any recurrent Spitz nevus.

PMID- 11979098
TI  - Clear cell 'sugar' tumor of the breast: another extrapulmonary site and review of
      the literature.
AB  - A group of lesions show morphologic and immunophenotypic evidence of
      differentiation toward a putative perivascular epithelioid cell. These so-called
      PEComas include angiomyolipoma, lymphangiomyoma, lymphangioleiomyomatosis, renal
      capsuloma, clear cell myomelanocytic tumor of the falciform ligament/ligamentum
      teres, and clear cell "sugar" tumor. PEComas are characterized by strong
      immunoreactivity with the HMB45 antibody and variable expression of muscle
      markers. This family of lesions may be composed of a spectrum of cells from
      epithelioid to spindle cells with clear to granular eosinophilic cytoplasm. One
      member of this family, composed of epithelioid cells with glycogen-rich clear
      cytoplasm, is descriptively called a clear cell "sugar" tumor. This tumor,
      originally described in the lung, is being recognized increasingly in
      extrapulmonary sites. We report a case of a primary extrapulmonary clear cell
      "sugar" tumor occurring in the right breast of a 16-year-old girl. The tumor was
      composed of clear epithelioid cells with abundant glycogen and distinct cell
      borders. The tumor showed strong immunoreactivity with HMB45 antibody and Melan
      A. There was focal vimentin staining. In addition, there was diffuse and strong
      nuclear staining for progesterone receptor. Antibodies to actins, S-100 protein,
      cytokeratins (AE1/AE3 and CAM5.2), desmin, and estrogen receptor were negative.
      The tumor was completely excised, and the patient is well without evidence of
      disease 9 months postexcision.

PMID- 11979099
TI  - Highly differentiated keratinizing squamous cell cancer of the cervix.

PMID- 11979100
TI  - Microcalcifications in the breast and the pathologist.

PMID- 11979107
TI  - Searching for solutions: the African crisis and the need for safe, simple and
      cheap prevention and therapy.

PMID- 11979108
TI  - Two long terminal repeat circles and persistent HIV-1 replication.
AB  - Building on the success of combination antiretroviral drug therapy will require a
      better understanding of the underlying basis for viral persistence.
      Characterization of the therapeutic, viral, and immunological factors that
      influence the size and stability of viral reservoirs will foster the development
      of strategies to control or eliminate HIV-1 from infected individuals. Here we
      review recent work aimed at delineating the complex interplay between viral
      replication, the immune system, and viral reservoirs. Finally, we address the
      implications and clinical significance of the residual replication that persists
      in infected individuals on potent antiretroviral therapy to evaluate both the
      possible risks and benefits of ongoing HIV-1 replication.

PMID- 11979110
TI  - Lymph nodes during antiretroviral therapy.
AB  - Highly active antiretroviral therapy rapidly reduces virus replication in the
      lymphoid tissue. Production of viral RNA, however, may still be detected in the
      lymphoid tissue despite negative plasma viremia. Continuing virus production and
      latent infection in resting cells seem to be important factors for viral rebound
      following treatment interruption. In parallel with viral suppression, immune
      activation is decreased and CD4+ T cell counts in the lymphoid tissue increase.
      It is still not known if there is a potential for complete viral suppression and
      immune reconstitution. Analyses of the lymphoid tissue during therapy may be
      helpful in addressing these issues.

PMID- 11979109
TI  - The potential for HIV fusion inhibition.
AB  - In recent years, exciting developments in the understanding of the multi-step HIV
      1 entry process have revealed potential approaches for therapeutic intervention
      that will compensate for the early disappointments of the soluble CD4 antigen
      approach. Although details of the HIV-1 fusion process are clearly complex, the
      proof-of-concept in the clinic provided by T-20 gives high hopes that new
      generation inhibitors of HIV fusion will be developed. This review highlights
      novel drug discovery technologies that are being employed in the search for such
      inhibitors.

PMID- 11979111
TI  - Implications of antiretroviral resistance on viral fitness.
AB  - Treatment of HIV infected patients with antiretroviral drugs often results in the
      emergence of virus variants with reduced sensitivity to these drugs. However, the
      viral load often remains partially suppressed below pretherapy levels, which
      might be explained by a reduced fitness of the drug resistant viral population.
      This review describes the effects of antiretroviral resistance development on the
      fitness of the viral population and its clinical implications.

PMID- 11979112
TI  - Structured treatment interruptions in antiretroviral management of HIV-1.
AB  - The consequences of treatment interruptions have been investigated in various
      patient populations. For patients with controlled viraemia, treatment
      interruption allowing viral rebound may boost HIV-1-specific immunity. The
      hypothesis that this will be sufficient to control HIV replication in the absence
      of treatment has received support in studies of patients initiating treatment
      during primary infections. In patients with chronic infection, treatment
      interruption has been shown to boost HIV-1-specific immunity in some cases. In
      patients with virological failure, despite drug-resistant virus, treatment
      appears to provide benefit, in that interruption results in a decrease in the CD4
      cell count and increases in plasma HIV-1-RNA levels. The removal of drug pressure
      allows the rapid shift to wild-type virus. Whether this will be of benefit to the
      patient is not clear. Treatment interruption may help reduce the accumulation of
      long-term toxicities.

PMID- 11979113
TI  - www.safer-sex.com.

PMID- 11979114
TI  - Can syphilis be eradicated from the world?
AB  - With the description of the complete genome sequence of Treponema pallidum, the
      declining rates of primary and secondary syphilis in many developed countries,
      and the continuing development of easier, cheaper, and more reliable diagnostics,
      the goal of worldwide syphilis eradication may be achievable. Although syphilis
      is easy to detect and cure given adequate access to and utilization of
      healthcare, many barriers exist on the way to its elimination and ultimate
      eradication. This review discusses current opinions regarding the plans,
      prospects and obstacles to worldwide syphilis eradication.

PMID- 11979115
TI  - New tests for bacterial sexually transmitted diseases.
AB  - Recent advances in diagnostic tests for sexually transmitted diseases include the
      development of a synthetic Venereal Disease Research Laboratory reagent that will
      improve the sensitivity and stability of nontreponemal serologic tests for
      syphilis. A second generation user friendly and high throughput nucleic acid
      amplification test for Chlamydia trachomatis and Neisseria gonorrhoeae has also
      been developed.

PMID- 11979116
TI  - Diagnosing human papillomaviruses: recent advances.
AB  - The biological importance of a group of human papillomaviruses, known as high
      risk human papillomaviruses, as the key causal agent for almost all cervical
      cancer has now been established. Many aspects of the natural history of high-risk
      human papillomaviruses as sexually transmitted infections and as oncogenic agents
      have been researched. Although human papillomavirus diagnosis is largely confined
      to DNA detection techniques in cervical smears, there is accumulating evidence
      that the best polymerase chain reaction and hybrid capture techniques are more
      sensitive and probably of similar specificity compared with cervical cytology as
      a triage test for women with borderline smear abnormalities and for screening
      older women. This is strong presumptive evidence that high-risk human
      papillomavirus testing could be useful in cervical screening. Current research is
      aimed at establishing a place for high-risk human papillomavirus testing in
      routine screening practice. Randomised clinical trials, long-term natural history
      studies, mathematical modelling, and economic and psychosocial studies are being
      used to demonstrate whether this testing can improve both the effectiveness and
      efficiency of cervical screening in a range of situations.

PMID- 11979117
TI  - Strategies for improving sexual health in ethnic minorities.
AB  - In many developed countries, ethnic minority communities bear the brunt of poor
      sexual health outcomes, with high rates of HIV/AIDS, sexually transmitted
      infections and their sequelae. Economic disadvantage, social exclusion and racism
      experienced by these communities all contribute to the observed inequalities.
      However, culturally prescribed attitudes and behaviours also play an important
      role. A review of the literature suggests that multifaceted and sustained
      approaches are needed to improve the sexual health of ethnic minority
      communities. Chief among these approaches are improving sexually transmitted
      infection surveillance and research tools; creating collaborative partnerships
      with communities; targeting high-risk groups and networks; and improving access
      to, and the utilization of, proven effective interventions.

PMID- 11979118
TI  - Male circumcision as a measure to control HIV infection and other sexually
      transmitted diseases.
AB  - There is growing epidemiological evidence from sub-Saharan Africa that male
      circumcision reduces the risk of HIV acquisition. We review the recent evidence
      of the protective effect on HIV and other sexually transmitted diseases,
      including discussion of possible biological mechanisms and highlighting the
      limitations of the observational studies on which these findings are based. We
      conclude by discussing the public health implications of these findings,
      including issues such as safety, acceptability, feasibility and cost
      effectiveness of promoting male circumcision in African populations.

PMID- 11979119
TI  - Endemic scalp ringworm: an object lesson in control of a common fungal infection.

PMID- 11979120
TI  - Bacterial skin infections in a tropical environment.
AB  - The subject of bacterial skin infection in the tropics has shown some significant
      advances in the past few years, although it is still relatively understudied. Of
      special interest is the emerging concern about the public health aspects of
      pyoderma, either primary or secondary to scabies, in developing countries. In
      addition, certain more unusual agents, such as Bacillus anthracis and
      Corynebacterium diphtheriae, continue to cause significant problems in some
      areas, while incidence of other tropical diseases, such as endemic
      treponematoses, has largely dropped.

PMID- 11979121
TI  - Necrotizing fasciitis.
AB  - Necrotizing fasciitis continues to occur due to beta-haemolytic streptococci but
      is now also recognized as being due to Vibrio spp. in fishermen and those in
      contact with warm water in the Gulf of Mexico and South-East Asia, including Hong
      Kong. Magnetic resonance image scanning has identified the extent of fasciitis
      and soft tissue oedema infiltrating fascial planes prior to necrosis presenting
      clinically and is a useful tool in early diagnosis. Surgical debridement or
      incisional drainage remains essential. An enhanced bactericidal response against
      beta-haemolytic streptococci has been found with a combination of penicillin and
      clindamycin. Intravenous immunoglobulin has been shown to reduce mortality if the
      necrotizing fasciitis is associated with the toxic shock syndrome, by decreasing
      the superantigen activity of the beta-haemolytic streptococci on cytokine release
      by T cells.

PMID- 11979122
TI  - Lyme disease in central Europe.
AB  - Lyme borreliosis is a fascinating disease, the aetiopathology of which is not yet
      completely known. Different subspecies of Borrelia burgdorferi sensu lato are
      responsible for the variable clinical course of the disease. Some new cutaneous
      (alopecia) and ocular (photophobia and retinal vasculitis) manisfestations have
      been described and the largest prospective study on erythema migrans during
      pregnancy was published during the last year. Optimal therapy of Lyme borreliosis
      is still lacking, but doxycycline, amoxicillin, penicillin, and ceftriaxone are
      recommended most frequently.

PMID- 11979123
TI  - Human papillomavirus antigens and T-cell recognition.
AB  - This review will summarize what is known about natural T-cell responses to human
      papillomavirus infections, including potential mechanisms for their dysregulation
      which may lead to the development of disease. We will also describe new
      strategies to enhance human papillomavirus specific T-cell responses following
      vaccination that are currently in development and recent reports on human vaccine
      trials with particular regard to the generation of appropriate T-cell responses.

PMID- 11979124
TI  - Endemic sporotrichosis.
AB  - Although first reported more than a century ago, sporotrichosis, caused by
      Sporothrix schenckii, still remains a poorly studied disease. Results from
      recently published studies on sporotrichosis in endemic areas are summarised and
      assembled with previous findings, providing a comprehensive review that
      highlights the needs for further research.

PMID- 11979125
TI  - Management of cutaneous leishmaniasis.
AB  - There is an urgent need for a safe, effective, easily administered and cheap
      treatment for cutaneous leishmaniasis. Unfortunately it remains elusive. There
      have been a number of contributions during the last year, but none will change
      present day management. The diagnosis of cutaneous leishmaniasis is established
      on the basis of a typical lesion, a history of exposure and demonstration of the
      parasite. Molecular methods, usually based on kinetoplast DNA, are being
      developed and used increasingly to diagnose and type the infecting organism.
      Pentavalent antimonials remain the mainstay of treatment.

PMID- 11979126
TI  - Current status and future prospects of the Global Lymphatic Filariasis Programme.
AB  - Lymphatic filariasis is recognized as one of the world's most disabling diseases.
      Adult lymphatic filarial nematodes live for several years; they infest the
      lymphatic and blood systems, and are transmitted via mosquito vectors. Acute and
      chronic disease can develop, manifesting as acute inflammation, hydrocoele,
      lymphoedema and elephantiasis. The development of a global programme for the
      elimination of lymphatic filariasis (focusing on disease caused by Wuchereria
      bancrofti) followed a resolution by the World Health Assembly in 1997 that
      endemic countries should develop programmes to eliminate lymphatic filariasis as
      a public health problem. This developed from an earlier recommendation by the
      International Task Force for Disease Eradication in 1993 that lymphatic
      filariasis was one of six diseases that could, in theory, be eradicated. Herein
      we review the current status and future prospects of the Global Lymphatic
      Filariasis Programme, which was launched in 2000.

PMID- 11979127
TI  - Community-acquired pneumonia: new guidelines for management.

PMID- 11979128
TI  - Pharmacokinetic and pharmacodynamic properties of antimicrobials in the therapy
      of respiratory tract infections.
AB  - Antimicrobial pharmacodynamics examines the relationship between the
      pharmacokinetics of a drug over time and its treatment effect.
      Pharmacokinetic/pharmacodynamic parameters have been shown to be predictors of
      the antimicrobial activity of a variety of drugs. The pharmacodynamic parameter
      linked to efficacy has been demonstrated to vary for different antimicrobial
      classes. Within an antimicrobial class, the magnitude of the pharmacodynamic
      parameter predictive of efficacy has been shown to be similar, as long as free
      drug levels in serum are considered. Treatment outcome predictions based upon
      parameter magnitudes have correlated well and have been useful for assessing the
      future course of both susceptible and resistant pathogens of the respiratory
      tract. This has been useful for the development of susceptibility breakpoints and
      antimicrobial treatment guidelines. Recent studies have begun to investigate the
      relationship between antimicrobial pharmacodynamics and the prevention of drug
      resistance.

PMID- 11979129
TI  - Streptococcus pneumoniae respiratory tract infections.
AB  - This review describes recent contributions to our understanding of pneumococcal
      pneumonia. Two genes have been described that encode enzymes involved with the
      biosynthesis of muropeptides. These enzymes may be novel antibiotic targets. The
      clinical impact of increasing antibiotic resistance on the treatment of pneumonia
      is the particular focus of the review. As resistant strains are more commonly
      associated with severe infections in patients with underlying disease, the
      interpretation of an association of resistance with poor clinical outcome is
      complicated.

PMID- 11979130
TI  - Mycoplasma pneumoniae infections.
AB  - Mycoplasma pneumoniae is a frequent cause of community-acquired respiratory
      infections in children and adults. Although the organism is felt to be the most
      frequent 'atypical' pathogen responsible for community-acquired pneumonia in
      adults, the prevalence of M. pneumoniae varies greatly from study to study,
      depending on the population and the diagnostic methods used. Recent studies have
      found the prevalence of M. pneumoniae in adults with pneumonia to range from 1.9
      to over 30%. M. pneumoniae is also a frequent cause of outbreaks of respiratory
      disease in institutional settings. However, the diagnosis of M. pneumoniae
      infection is hampered by the lack of standardized, rapid, specific methods. This
      problem was illustrated by the results of an investigation of an outbreak of M.
      pneumoniae infection in a federal training facility. Accurate diagnosis required
      a combination of polymerase chain reaction and serology, as IgM antibodies were
      not present early in the course of the infection in many patients. Several papers
      evaluating various serological and polymerase chain reaction assays were
      published during the period of this review. An assessment of the actual
      performance of these tests was also hampered by the lack of standardized
      comparative methods. M. pneumoniae is susceptible in vitro to macrolides,
      tetracyclines and quinolone antibiotics; however, data are limited on the
      microbiological efficacy of these agents. Several pneumonia treatment studies
      were published during this period, practically all of them based the diagnosis of
      M. pneumoniae infection on serology; different methods and criteria were used in
      each study, and thus the microbiological efficacy could not be assessed. The
      Infectious Disease Society of America recently stated in their revised Practice
      Guidelines for the Management of Community-Acquired Pneumonia in Adults that, as
      there were no diagnostic tests available that reliably and rapidly detect M.
      pneumoniae, therapy must usually be empirical.

PMID- 11979131
TI  - Anaerobic pleuropulmonary infection.
AB  - Obligate anaerobes are the predominant constituents of normal oropharyngeal flora
      and produce pleuropulmonary infection in patients who are prone to aspirate.
      Obtaining material from these patients for culture from the site of infection
      that is uncontaminated by normal flora is problematic. In-vitro cultivation of
      obligate anaerobes requires rigorous anaerobic techniques and susceptibility
      testing of obligate anaerobes is not standardized in many clinical microbiology
      laboratories. Few clinical trials of drugs have been done in patients with
      laboratory documented or putative anaerobic pulmonary infection. For these
      reasons the diagnosis and therapy of anaerobic pulmonary infection are frequently
      empirical and guided by published studies of in-vitro activity against collected
      clinical isolates. Several new drugs that have in-vitro activity against obligate
      anaerobes have recently become available for empirical treatment of pneumonia.

PMID- 11979132
TI  - Bronchiectasis.
AB  - Bronchiectasis is a structural derangement of the bronchial wall that is
      characterized by airway dilatation and bronchial wall thickening. As a result of
      this abnormality, chronic inflammation and secondary microbial infections occur,
      which cause additional damage to the bronchi. Recent insights into the potential
      pathophysiological mechanisms of bronchiectasis, as well as improvements in
      computed tomography and the development of new pharmacological agents, might help
      to improve the clinical management of this chronic infective/inflammatory
      disorder.

PMID- 11979133
TI  - Update on influenza and other viral pneumonias.
AB  - Major developments during the past 5 years concerning influenza prevention by
      vaccination and treatment with neuraminidase inhibitors are reviewed. These have
      been accompanied by increased media interest in related issues: pressures on
      hospital admissions, ethical concerns and controls on prescribing limiting
      professional autonomy. The new live attenuated influenza vaccines, adjuvanted
      vaccines and the emerging recombinant DNA vaccines are discussed. Recent
      information on neuraminidase inhibitor antivirals, surveillance for resistant
      viruses, the prospects for near patient tests (i.e. tests that can be used near
      the patient to improve immediate patient management or in the laboratory to give
      rapid feedback for physicians) and the clinical significance of other respiratory
      viruses are highlighted. The benefits of recent advances provide challenges for
      health care delivery and public acceptance as great as those involved in their
      scientific development.

PMID- 11979134
TI  - Hantavirus pulmonary syndrome: at the crossroads.
AB  - The initial identification in 1993 of hantavirus pulmonary syndrome as a novel,
      highly fatal respiratory illness among American Indians in the southwestern USA
      in 1993 opened the window to the recognition of a well-established pan-American
      zoonosis with a myriad of causative viruses and rodent vectors, although all are
      New World hantaviruses among New World sigmodontine rodents. The clinical
      spectrum of symptoms has also been expanded to include asymptomatic infection
      through to fulminant hemorrhagic fever. Although the use of ribavirin, an
      antiviral drug, was disappointing in an early, open-labeled trial, early
      detection and supportive care is much better refined. However, much work remains
      in probing the pathogenesis of this syndrome to help define and explore
      therapeutic options and the mechanism of person-to-person transmission with Andes
      virus, one of the viruses that cause hantavirus pulmonary syndrome. Current
      remote sensing efforts and longitudinal ecologic investigations need to be
      expanded in order to focus prevention efforts better.

PMID- 11979135
TI  - Gliotoxin, an inhibitor of nuclear factor-kappa B, attenuates peptidoglycan
      polysaccharide-induced colitis in rats.
AB  - Gliotoxin is a fungal metabolite that has immunosuppressive properties. First, we
      determined if gliotoxin could inhibit bacterial peptidoglycan-polysaccharide
      stimulated tumor necrosis factor-alpha production, as well as nuclear factor
      kappa B (NF-kappaB), in a rat macrophage (NR8383) cell line. Next, the apoptosis
      inducing potential of gliotoxin was also evaluated in this cell line. Finally, we
      evaluated whether gliotoxin could reduce peptidoglycan-polysaccharide-induced
      colitis in rats. Gliotoxin (2 mg/kg/day) was dosed from day 14 after the initial
      intramural colonic injection of peptidoglycan-polysaccharide until day 21. A
      gross colonic injury score, myeloperoxidase activity, and cytokine levels were
      all evaluated on day 21. Gliotoxin dose dependently inhibited cytokine
      production, as well as NF-kappaB, and also induced apoptosis in the NR8383 cell
      line. On day 21, gliotoxin significantly reduced gross colonic injury (adhesions,
      nodules, mucosal lesions) in rats. Gliotoxin-treated rats also had partially
      normalized biochemical indices of colitis, such as colonic cytokine levels. The
      colonic level of NF-kappaB was also partially normalized in gliotoxin treated
      rats. Gliotoxin also exhibited an antiarthritis effect in peptidoglycan
      polysaccharide-treated rats. In summary, gliotoxin effectively attenuated the
      chronic reactivation phase of peptidoglycan-polysaccharide-induced colitis. This
      anticolitis effect may be related to the inhibition of NF-kappaB in Lewis rats.

PMID- 11979136
TI  - Clinical significance of granuloma in Crohn's disease.
AB  - Crohn's disease (CD) is diagnosed from information obtained clinically,
      pathologically, and radiologically. One important pathologic finding is a
      granuloma, which is helpful when a positive diagnosis of CD will affect
      treatment. Whether the presence of a granuloma has any clinical implication is
      not clear. We conducted a retrospective study to determine whether a granuloma
      found on a biopsy sample is associated with disease severity, fistulizing or
      perianal disease, frequent relapses, and extraintestinal manifestations. Eighty
      two patients were identified who had a biopsy or bowel resection for CD between
      1990 and 1994 at a tertiary referral center; 21 (25.6%) had a granuloma. This
      group was compared with a group of 61 patients without a granuloma. Forty-five
      percent were male (n = 37), mean age at diagnosis was 42.6 years (median, 39.5
      years), mean disease duration at presentation was 8.8 years (median, 4.8 years),
      and mean follow-up duration was 2 years (range, 1 day to 10.2 years). No
      significant differences were demonstrated between the two groups by the Fisher
      exact test with regard to fistulizing or perianal disease, oral aphthous ulcers,
      disease severity, axial or peripheral arthralgia, episcleritis, anterior uveitis,
      erythema nodosum, or pyoderma gangrenosum.

PMID- 11979137
TI  - Use of complementary therapies by patients with IBD may indicate psychosocial
      distress.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is used increasingly by
      patients with chronic diseases. We have assessed the use of CAM in general
      medicine and gastrointestinal outpatients focusing particularly on factors
      predisposing to its use in patients with inflammatory bowel disease (IBD).
      METHODS: 239 consecutive patients attending gastrointestinal and general medical
      outpatient clinics answered a questionnaire about their use of CAM: patients with
      IBD also completed a validated disease-specific quality of life (QOL)
      inflammatory bowel disease questionnaire (IBDQ). RESULTS: 26% of all patients
      used CAM, most commonly herbal remedies (43%). CAM was used significantly more by
      younger than older patients and by single than married or widowed ones. There
      were no differences by gender or ethnicity. More patients with irritable bowel
      syndrome used CAM than those with other diagnoses. In IBD patients, CAM users had
      significantly poorer QOL scores for emotional and social factors than nonusers.
      53% of users stated that CAM alleviated their symptoms. CONCLUSIONS: Use of CAM
      is common in gastroenterological outpatients, particularly if they are young,
      single, or have irritable bowel syndrome (IBS). Most patients deem it helpful. In
      IBD, poor QOL predisposes to use of CAM. Conversely, use of CAM may serve as a
      marker of emotional or social unease in these patients. Physicians need to be
      aware of widespread usage of CAM by their patients.

PMID- 11979138
TI  - Distribution of Peyer's patches in the distal ileum.
AB  - BACKGROUND AND AIMS: Peyer's patches play a major role in intestinal immunity,
      are portals of entry for significant pathogens, and may be important in Crohn's
      disease. Whereas their microscopic anatomy and immune function are well
      described, surprisingly little is known of their macroscopic anatomy and
      distribution. Our aim was to assess their number, area, and distribution in the
      normal distal ileum, with particular reference to patient age. METHODS: Distal
      ilea (200 cm) obtained at autopsy from 55 adults without intestinal disease were
      opened along the mesenteric border, fixed in acetic acid, and transilluminated.
      Peyer's patches were counted, and the length, breadth, and distance from the
      ileocecal valve were recorded. RESULTS: Patches were most numerous in the
      terminal 10-15 cm where they formed a lymphoid ring. More proximal patches were
      oval, antimesenteric, and irregularly spaced. By area, 46% of patch tissue
      occurred in the terminal 25 cm. The mean number of patches ranged from 29.4 +/-
      5.4 in the youngest group studied, to 19.0 +/- 3.0 in the oldest. Total patch
      area was greatest in the group aged 21-30 (47.4 +/- 1.0 cm2). CONCLUSION: Peyer's
      patches are concentrated in the distal 25 cm of ileum but extend proximally for
      200 cm. The variation in their size, shape, and distribution in different
      individuals is greater than often appreciated and may influence the presentation
      of diseases centered on these structures.

PMID- 11979139
TI  - Delayed hypersensitivity reaction and acute respiratory distress syndrome
      following infliximab infusion.
AB  - Infliximab, a chimeric human/murine monoclonal antibody directed against the
      proinflammatory cytokine tumor necrosis factor alpha, is an effective therapy for
      Crohn's disease (CD) and rheumatoid arthritis refractory to standard medical
      treatment. We report a case of adult respiratory distress syndrome associated
      with infliximab therapy. A 33-year-old white male presented with an exacerbation
      of CD and was treated with his second infliximab infusion (15 months following
      the first infusion). Within 7 days he developed arthralgias, myalgias, and fever,
      followed by respiratory failure. He required intubation and mechanical
      ventilation. Open lung biopsy demonstrated eosinophilic pneumonia. Human
      antichimeric antibodies were present at high concentrations. An extensive
      investigation for infectious etiologies was negative. The patient was treated
      with intravenous corticosteroids, and fully recovered after a prolonged
      hospitalization. We review the infectious and immunologic complications of
      infliximab.

PMID- 11979141
TI  - Writing clinical research grant applications.

PMID- 11979140
TI  - Successful treatment of an acute flare of steroid-resistant Crohn's colitis
      during pregnancy with unfractionated heparin.
AB  - Recent reports suggest that unfractionated heparin may be a useful adjunct in the
      treatment of inflammatory bowel disease (IBD). We report the successful use of
      subcutaneous unfractionated heparin to treat a moderate-to-severe flare of
      Crohn's disease during pregnancy, which was refractory to standard therapy. The
      patient received 10,000 units of unfractionated heparin subcutaneously twice a
      day after her Crohn's colitis failed to come under remission with intravenous
      corticosteroids. Heparin was continued throughout her pregnancy. Following
      initiation of adjunctive heparin therapy, the patient experienced a rapid
      clinical response, was able to discontinue intravenous steroids, discharge from
      the hospital, and ultimately deliver a healthy term newborn. Although there is
      extensive obstetric experience with heparin in the treatment of thrombosis
      associated with pregnancy, there is limited information regarding its use in IBD
      patients during pregnancy. Because heparin has an established track record in
      maternal-fetal medicine, this agent may be considered in women who suffer an
      inflammatory flare of IBD during pregnancy who have not responded to standard
      treatment.

PMID- 11979143
TI  - Role of infections in the manifestation or reactivation of inflammatory bowel
      diseases.
AB  - The etiology of inflammatory bowel disease (IBD) is unknown. In addition to
      genetic and environmental factors, microorganisms have been discussed as possibly
      playing an important role. Recent reports in the literature do not suggest that a
      specific persistent infection causes IBD, but indicate that enteric pathogens
      could cause initial onset of IBD and are associated with reactivation of
      quiescent disease. Despite their self-limited character, these infections
      initiate a cascade of inflammatory events leading to chronic, relapsing disease
      in a genetically susceptible host ("hit-and-run" hypothesis). Epidemiological and
      microbiologic studies suggest that enteropathogenic microorganisms play a
      substantial role in the clinical initiation and relapses of IBD. However, similar
      to traveler's diarrhea, the frequency of infections in the first manifestation
      and in relapses of IBD is probably understated, due to the problems in detecting
      enteric pathogens. Thus microbiologic screening is helpful in patients with
      flares of IBD for optimal medical treatment.

PMID- 11979142
TI  - Recent advances in understanding NF-kappaB regulation.

PMID- 11979144
TI  - Steroids for Crohn's disease--an appreciation and a vote of confidence.

PMID- 11979146
TI  - Controversies in IBD. Serologic tests are helpful in managing inflammatory bowel
      disease.

PMID- 11979147
TI  - Serologic tests are not helpful in managing inflammatory bowel disease.

PMID- 11979149
TI  - Efficacy of the iodine-free computed tomography liver contrast agent, Dy-EOB
      DTPA, in comparison with a conventional iodinated agent in normal and in tumor
      bearing rabbits.
AB  - RATIONALE AND OBJECTIVES: To investigate the efficacy of the new liver-specific x
      ray contrast agent, Dy-EOB-DTPA, in rabbits with VX2 liver tumors by spiral
      computed tomography (CT) in comparison to iopromide. MATERIALS AND METHODS: The
      time course of liver enhancement was determined in five groups of two normal
      anesthetized rabbits, which received intravenous injections of Dy-EOB-DTPA before
      anesthesia at a dose of 0.5 mmol/kg. Fifteen, 30, 45, 60, and 90 minutes after
      administration spiral CT images were obtained and the attenuation in the livers
      were determined. A second group of ten rabbits with implanted VX2 tumors received
      in a random crossover design either Dy-EOB-DTPA at a dose of 0.5 mmol/kg or, 1
      day later, iopromide at a dose of 600 mg iodine/kg. CT images were obtained 60
      minutes after Dy-EOB-DTPA administration and both in the arterial and portal
      venous phases after iopromide injection. Three radiologists evaluated the images.
      The rabbits were killed, and their livers were investigated histologically for
      liver tumors. RESULTS: In normal animals, 0.5 mmol/kg Dy-EOB-DTPA resulted in a
      liver enhancement of 30 HU during the whole observation period of 90 minutes. In
      tumor-bearing animals, histology revealed 14 implanted tumors of 3-20 mm
      diameter. Sixty-five percent of the tumors were below 10 mm. Dy-EOB-DTPA was able
      to detect 13 tumors (93%), iopromide 11 (79%) both in the arterial and in the
      portal-venous phase. The difference was statistically not significant. In plain
      CT, seven tumors (50%) were found (P < 0.01 vs iopromide and Dy-EOB-DTPA). One
      scar and two sites of necrosis were detected by each of the methods. CONCLUSION:
      Dy-EOB-DTPA injection at a dose of 0.5 mmol/kg resulted in a long-lasting
      detectability of 93% of all implanted tumors versus 79% found with iopromide.

PMID- 11979150
TI  - Antiproliferative effects of the antiallergic agent azelastine on human aortic
      smooth-muscle cells: an in vitro study.
AB  - RATIONALE AND OBJECTIVES: The aim of the study was to examine the effects of
      azelastine on proliferation, clonogenic activity, cell-cycle, and migration of
      human aortic smooth-muscle cells (haSMCs) in vitro. METHODS: HaSMCs were treated
      for 4 days with azelastine (1 micromol/L, 25 micromol/L, 50 micromol/L). Half of
      the treated groups were incubated again with azelastine, the other half received
      azelastine-free medium every 4 days until day 20. The growth kinetics and
      clonogenic activity were assessed. The cell-cycle distribution was investigated
      by FACS -- analysis and the migratory ability was evaluated. RESULTS: Azelastine
      inhibited the proliferation and the clonogenic activity of haSMCs in a dose
      dependent manner. A G2/M-phase block was induced and the migratory ability was
      significantly impaired. CONCLUSION: Azelastine has the potential to inhibit the
      proliferation of haSMCs. If a sufficient dose can be applied either systemically
      or locally it could be a valuable substance to prevent restenosis.

PMID- 11979151
TI  - X-ray digital subtraction angiography with 1 mol/L gadobutrol: results from a
      comparative porcine study With iodinated contrast agents.
AB  - RATIONALE AND OBJECTIVES: To evaluate prospectively diagnostic accuracy of 1
      mol/L gadobutrol as a contrast agent for intraarterial x-ray digital subtraction
      angiography (DSA) in comparison to iodinated, nonionic contrast media and 0.5
      mol/L gadolinium-DTPA. METHODS: Flush arteriograms (ascending, descending,
      abdominal aorta, iliac, and femoral arteries) and selective angiograms (carotid,
      renal, and visceral arteries) were obtained from bilateral femoral arterial
      access (5 F sheaths) in 10 domestic pigs (70 kg body weight). Digital subtracted
      angiograms were obtained during injection of undiluted 1 mol/L gadobutrol, 300 mg
      I/mL iopromide, or 0.5 mol/L gadopentetate. Injection parameters (volume and
      velocity) were similar for all three contrast agents. In paired arteries, two
      different contrast media were used during the same angiographic run. Diagnostic
      quality and accuracy of the angiograms were evaluated on a three-step scale by
      three independent blinded investigators. RESULTS: Sufficient nonselective
      angiographic images were obtained in 90% of cases using iodinated contrast
      material. Gadobutrol achieved sufficient nonselective angiograms in 64%.
      Selective angiograms were sufficient in 98% using iodinated contrast material,
      90% using 1 mol/L Gadobutrol and 48% using 0.5 mol/L Gd-DTPA. Adverse reactions
      to any of the used contrast agents were not noted. CONCLUSION: One mol/L
      Gadobutrol solution allows x-ray digital subtraction angiography with a
      diagnostic accuracy equivalent to 300 mg/mL iodinated contrast media, if
      selective injections are performed. Flush aortograms are of inferior image
      quality to iodinated contrast material.

PMID- 11979152
TI  - Optimization of contrast dosage for gadobenate dimeglumine-enhanced high
      resolution whole-body 3D magnetic resonance angiography.
AB  - RATIONALE AND OBJECTIVES: To determine the optimal dose of gadobenate dimeglumine
      for diagnostic high-resolution whole-body 3D-MR angiography. METHODS: Ten healthy
      volunteers were examined three times with an ascending dose of Gd-BOPTA
      (0.1/0.2/0.3 mmol/kg BW). Three-dimensional data sets were collected with a
      rolling table platform (AngioSURF; MR-Innovation GmbH, Essen, Germany) which
      integrates the torso surface coil, using a 3D FLASH sequence at five stations
      from carotid arteries to the trifurcation vessels in 72 seconds. SNR- and
      contrast-to-noise-values were calculated for 30 segments per patient. For
      qualitative evaluation a 4-point-visualization scale was used. RESULTS: Overall,
      significantly (P < 0.05) higher signal-to-noise values and CNR values were
      determined for Gd-BOPTA at a dose of 0.2 and 0.3 mmol/kg compared with 0.1
      mmol/kg. Similarly, the qualitative analysis demonstrated image quality to be
      superior with 0.2 and 0.3 mmol/kg compared with 0.1 mmol/kg (P < 0.05).
      Qualitative and quantitative assessment failed to demonstrate a statistically
      significant difference between 0.2 and 0.3 mmol/kg BW (P > 0.05). CONCLUSION: A
      dose of 0.2 mmol/kg BW Gd-BOPTA rendered diagnostic image quality in all vascular
      segments of all volunteers.

PMID- 11979154
TI  - Regional lung functional impairment in acute airway obstruction and pulmonary
      embolic dog models assessed with gadolinium-based aerosol ventilation and
      perfusion magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: Gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)
      based aerosol ventilation and perfusion magnetic resonance (MR) images were used
      to define regional functional impairment in acute airway obstruction (AO) and
      pulmonary embolic (PE) dog models. METHODS: The aerosol study was performed in 10
      anesthetized normal dogs in a supine position during 20-minute spontaneous
      inhalation of an aerosol of 100- or 200-mmol-Gd/L Gd-DTPA solute produced by an
      ultrasonic nebulizer in an open-circuit delivery system, combined with a dynamic
      perfusion study after a 3-second intravenous bolus injection of a 0.1 mmol/kg
      dose of Gd-DTPA. These MR studies were also performed in the same 10 dogs
      approximately 30 minutes after obstructing the segmental (n = 6) or lobar (n = 4)
      bronchus with a balloon catheter, and in another six dogs after segmental (n = 6)
      and lobar (n = 4) pulmonary arterial embolization with enbucrilate. Regional lung
      enhancement was assessed on time-signal intensity (SI)-curves and ventilation-
      and perfusion-weighted images produced by a subtraction technique. RESULTS: The
      normal lungs were gradually and gravity-dependently enhanced with time after Gd
      DTPA aerosol inhalation regardless of the respiratory SI changes, except for
      three animals with the fastest breathing rate. The averaged maximal relative lung
      SI increase against the baseline in the successful animals was significantly
      greater in the slowly and deeply breathing animals than in the fast and shallow
      breathing animals, regardless of the difference in Gd-concentration (100 mmol
      Gd/L: 153.3% +/- 69.7% vs. 54.2% +/- 23%; P < 0.001; and 200 mmol Gd/L: 189.7% +/
      68.0% vs. 75.6% +/- 42.2%; P < 0.0001, respectively). There was an additional
      enhancement of 382% +/- 101 in the ventral lung and 722% +/- 160 in the dorsal
      lung on the pulmonary arterial phase perfusion image even in the slowly and
      deeply breathing animals who inhaled 200-mmol-Gd/L aerosol, and the enhancement
      effect was significantly greater compared with that with the aerosol (P <
      0.0001). The ventilation- and perfusion-weighted images clearly defined the
      regionally matched perfusion-ventilation deficits in all the AO models, and the
      regionally mismatched perfusion-ventilation in all the PE models. CONCLUSION: Gd
      based aerosol can provide efficient lung enhancement in spontaneously and
      adequately breathing animals, using a relatively noninvasive aerosol delivery
      system. The combined use of Gd-based perfusion MR imaging may be acceptable for
      defining regionally impaired function associated with acute AO and PE.

PMID- 11979153
TI  - Double-blind, efficacy evaluation of gadobenate dimeglumine, a gadolinium chelate
      with enhanced relaxivity, in malignant lesions of the brain.
AB  - BACKGROUND AND PURPOSE: The diagnostic efficacy of gadobenate dimeglumine (Gd
      BOPTA) was compared with that of gadodiamide (Gd DTPA-BMA) in patients with
      primary malignant tumors or metastases of the brain. METHODS: A subset of
      patients was evaluated from the 410 enrolled in the United States in phase III
      central nervous system clinical trials with gadobenate dimeglumine. From these
      trials, there were 82 patients with intraaxial malignant neoplasms of the brain,
      the focus of the current study. Patients were randomized to one of three
      incremental dosing regimens. Imaging with gadodiamide at doses of 0.1 and 0.3
      mmol/kg was compared with gadobenate dimeglumine at doses of 0.05 and 0.15
      mmol/kg and at doses of 0.1 and 0.2 mmol/kg. The on-site physician, patient, and
      all off-site reviewers were blinded to the agent injected and the administered
      dose. Scans were obtained before contrast administration and within 5 minutes
      after administration of each dose. The two contrast injections in any one patient
      were separated by 15 minutes. An independent laboratory performed signal
      intensity measurements. The magnetic resonance (MR) films were evaluated for
      level of diagnostic information, number of lesions detected, and confidence in MR
      imaging diagnosis by two independent board-certified neuroradiologists
      unaffiliated with any study site. RESULTS: The lesion-to-brain signal intensity
      ratio after a dose of 0.1 mmol/kg gadobenate dimeglumine was higher than that
      after a dose of 0.1 mmol/kg gadodiamide, with this result statistically
      significant (P = 0.02). After the second dose of contrast, results were
      comparable in all three groups. The level of diagnostic information contained on
      the MR films increased significantly for all three groups from pre- to
      postcontrast for both the first and second administered doses. In between-group
      comparisons, the level of diagnostic information was similar after the first
      contrast dose for all three dosing regimens. This was also true after the second
      contrast dose. For all three groups, the number of lesions detected increased
      significantly postdose (whether first or second). Confidence in MR diagnosis
      increased from predose to postdose for all three groups, with no statistically
      significant difference between groups. CONCLUSION: Gadobenate dimeglumine, used
      at slightly lower doses, is comparable to gadodiamide in terms of efficacy in
      imaging of malignant intraaxial brain lesions. As with other gadolinium chelates,
      higher doses (0.15 and 0.2 mmol/kg) of gadobenate dimeglumine offer greater
      diagnostic information.

PMID- 11979155
TI  - Effect of resovist on rats with different severities of liver cirrhosis.
AB  - RATIONALE AND OBJECTIVES: Whether the degree of diffuse hepatic damage is
      correlated with the signal change on MR images after injection of
      superparamagnetic iron oxide (SPIO) particles was investigated. In addition, we
      investigated whether hepatic function deteriorates after injection of SPIO.
      METHODS: Seventy-six female Sprague-Dawley rats aged 3 to 4 weeks were given
      drinking water containing 0.03% thioacetamide (TAA) for 4 or 12 weeks to induce
      two grades of liver injury. Seventeen normal rats were served as a control.
      Normal and model rats were administered Resovist (10 micromol Fe/kg), and signal
      intensities in the liver on MR images obtained at 4.7 T were measured up to 60
      minutes after injection (n = 5). The model rats were injected with 10 times the
      envisaged dose of Resovist (100 micromol Fe/kg) or saline as a control substance,
      and blood parameters were measured at 4, 24, and 48 hours after injection (n = 5
      or 6). At 4 hours after injection, iron and Kupffer cells in the liver were
      stained (n = 3). RESULTS: Maximal signal reduction in the liver occurred 15
      minutes after injection in all groups. The reduced signal persisted for 60
      minutes after injection. However, the degree of maximal signal reduction in the
      model rats was significantly less than that in the normal rats (P < 0.05, 0.01).
      Signal reduction in the 12-week group was less than that in the 4-week group. In
      control rats, the number of iron-positive cells increased by 22 cells per area
      (0.065 mm(2)) following treatment with Resovist. In the 4-week and 12-week
      groups, numbers of iron-positive cells increased by 13 and 11 cells,
      respectively. There was no statistically significant difference in the number of
      Kupffer cells between control and model rats. No significant change was observed
      in blood parameters with Resovist. CONCLUSION: The MR signal induced by Resovist
      depended on the degree of phagocytic activity in the liver. The safety profiles
      of Resovist remained unchanged even at 10 times the imaging dose.

PMID- 11979157
TI  - Relative cost-effectiveness of extensive and light multidisciplinary treatment
      programs versus treatment as usual for patients with chronic low back pain on
      long-term sick leave: randomized controlled study.
AB  - STUDY DESIGN: A subgroup of 195 patients with chronic low back pain, being part
      of a larger study of other musculoskeletal patients, were included in a
      randomized controlled prospective clinical study. OBJECTIVES: To evaluate the
      outcome in terms of return to work and cost-effectiveness of a light
      multidisciplinary treatment program with an extensive multidisciplinary program
      and treatment as usual initiated by their general practitioner. SUMMARY OF
      BACKGROUND DATA: Light multidisciplinary programs seem to reduce sick leave in
      patients with subacute low back pain. There are few, if any, previous studies of
      the effectiveness of light versus extensive multidisciplinary treatment on return
      to work in patients with chronic low back pain. METHODS: Patients with chronic
      low back pain (n = 195), on an average sick-listed for 3 months, were included.
      The patients were randomized to a light multidisciplinary treatment program, an
      extensive multidisciplinary program, or treatment as usual by their primary
      physician. Full return to work was used as outcome response, and follow-up was 26
      months after the end of treatment. Cost-benefit was calculated for the treatment
      programs. RESULTS: In men significantly better results for full return to work
      were found for the light multidisciplinary treatment compared with treatment as
      usual, but no differences were found between extensive multidisciplinary
      treatment and treatment as usual. No significant differences between any of the
      two multidisciplinary treatment programs and the controls were found for women.
      Productivity gains for the society from light multidisciplinary treatment versus
      "treatment as usual" of 57 male patients with low back pain would during the
      first 2 years accumulate to U.S. $852.000. CONCLUSIONS: The light
      multidisciplinary treatment model is a cost-effective treatment for men with
      chronic low back pain.

PMID- 11979156
TI  - Pharmacokinetics and safety of gadobenate dimeglumine (multihance) in subjects
      with impaired liver function.
AB  - RATIONALE AND OBJECTIVES: To characterize the pharmacokinetics of gadolinium and
      to evaluate the safety of gadobenate dimeglumine (Gd-BOPTA) compared with
      placebo, in subjects with impaired liver function. METHODS: Volunteer adult
      subjects with hepatic impairment (Child-Pugh classification B or C) received,
      randomly and in double-blind fashion, either 0.1 mmol/kg gadobenate dimeglumine
      (n = 11) or placebo (n = 5) by intravenous injection. Blood and urine gadolinium
      concentrations were determined by ICP-AES and data were analyzed by compartmental
      and noncompartmental modeling. A full safety evaluation was performed. No
      magnetic resonance imaging was performed. RESULTS: A bi-exponential model fit the
      gadolinium blood concentration-time data for 10 of 11 subjects administered Gd
      BOPTA. The mean (CV%) distribution and elimination half-lives for these subjects
      were 0.18 (71.9) and 2.18 (44.2) hours, respectively. Non-parametric analysis of
      all 11 subjects revealed a mean (CV%) area under the curve [0-inf] of 138 (41.9)
      microg(Gd).h/mL. Mean (CV%) values for blood clearance, steady-state volume of
      distribution, and renal clearance were 172 (36.0) mL/minute, 22.9 (16.7) L, and
      142 (49.0) mL/minute, respectively. A mean (CV%) of approximately 80% (24.5) of
      the administered dose was excreted in urine during 60 to 72 hours. No safety
      concerns were apparent. CONCLUSION: Hepatic impairment did not modify the
      pharmacokinetics of gadobenate dimeglumine compared with values reported
      elsewhere for healthy subjects. The contrast agent was well tolerated and safe
      with an overall incidence of adverse events comparable to that of placebo.

PMID- 11979161
TI  - Measurement of cadaver lumbar spine motion segment stiffness.
AB  - STUDY DESIGN: Prospective. OBJECTIVES: To measure lumbar spine motion segment
      stiffness and relate it to the degree of disc degeneration. SUMMARY OF BACKGROUND
      DATA: The association between the instability of the lumbar spine motion segment
      and disc degeneration remains unclear. The traditional method for determining
      motion segment instability at the time of decompressive surgery is a manual test
      performed by the surgeon. To quantify instability of the lumbar spine, a
      vertebrae distractor was developed in the authors' laboratory to measure motion
      segment stiffness by applying a defined load at a constant rate. METHODS: Lumbar
      stiffness was measured by subjecting cadaver lumbar spine motion segments to a
      constant rate flexion-traction load and recording the magnitude of the resistance
      to distraction versus the range of motion. Disc degeneration was measured by
      pressure-volume discography and by grading of disc morphology. RESULTS: Motion
      segment stiffness decreased with the initial stages of disc degeneration and then
      increased with severe disc degeneration. This measure of motion segment stiffness
      correlated well with a manual stiffness measure. CONCLUSIONS: The observed
      results follow an accepted hypothesis of motion segment instability associated
      with disc degeneration.

PMID- 11979160
TI  - mRNA expression of cytokines and chemokines in herniated lumbar intervertebral
      discs.
AB  - STUDY DESIGN: The mRNA expressions of cytokines and chemokines were assessed in
      herniated lumbar disc specimens. OBJECTIVES: To investigate whether the mRNAs of
      interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha, RANTES, IL-8, IL-10,
      and transforming growth factor (TGF)-beta are expressed in surgically obtained
      herniated disc specimens; and to discover which of them are the predominant
      cytokines associated with the clinical symptoms and signs, and whether any
      differences in the mRNA expression exist depending on the different types of disc
      herniations. SUMMARY OF BACKGROUND DATA: It has been postulated that cytokines
      are involved in causing radicular leg pain in lumbar disc herniations. Although a
      few studies have been done on lumbar disc herniations concerning IL-1alpha and
      TNF-alpha, almost none has been carried out in the cases of the other of
      cytokines and chemokines. METHODS: Using a reverse transcription-polymerase chain
      reaction, mRNA expressions of cytokines and chemokines were investigated in
      herniated disc specimens. The straight leg raising test, development of radicular
      pain by back extension, symptom duration, pain intensity using a visual analogue
      scale, and herniation types were described. RESULTS: The mRNAs of IL-8, TNF
      alpha, IL-1alpha, RANTES, and IL-10 were expressed in 16 (70%), 15 (65%), 9
      (39%), 4 (17%), and 2 (9%) of the 23 herniated disc specimens, respectively. The
      mRNA of TGF-beta was expressed in 5 of 10 specimens (50%). IL-8 mRNA expression
      was associated with the development of radicular pain by back extension and short
      symptom duration (average 3.8 weeks). The mRNAs of IL-1alpha were expressed more
      frequently in transligamentous extensions than in subligamentous extensions, but
      the expression was weak. CONCLUSION: Interleukin-8 appears to be associated with
      development of radicular pain by back extension and to be activated on acute or
      subacute disc herniations. IL-8 seems to participate in the pathomechanism of
      nerve root inflammation in lumbar disc herniations, which implies that it may be
      considered a target for therapeutic intervention.

PMID- 11979162
TI  - In vitro stability of FRA spacers with integrated crossed screws for anterior
      lumbar interbody fusion.
AB  - STUDY DESIGN: Mechanical testing of human lumbar functional spine units was
      carried out after instrumenting the disc space with femoral ring allografts
      (FRAs) with and without integrated crossed anterior screws applied into the
      adjacent bodies. OBJECTIVES: To assess the stability of FRA construct with and
      without the integrated crossed anterior screws and to compare that with the
      intact specimen. SUMMARY OF BACKGROUND DATA: Most modern methods of achieving
      anterior lumbar intervertebral fusion rely on the use of interbody spacers to
      restore and maintain intervertebral height, overall alignment, and stability
      while facilitating arthrodesis. The FRAs have the advantage of biologic
      compatibility but may not have enough stability when used as stand-alone devices.
      FRA spacers alone are less stiff in torsion and extension compared with other
      instrumented constructs. Increased motion could lead to higher failure rates
      because of graft migration and pseudarthrosis. This makes the use of
      supplementary anterior or posterior fixation necessary. The current authors
      hypothesized that the addition of anterior integrated crossed screws applied
      through the FRA spacer into the adjacent vertebral bodies would increase the
      stability of the FRA spacer in extension and torsion in the absence of further
      posterior instrumentation. METHODS: Seven fresh-frozen human cadaveric lumbar
      spine functional spine units were tested applying cantilever bending moments in
      flexion, lateral bending, torsion, and extension. The specimens were tested in
      the following sequence: intact, with FRA spacer alone and with FRA spacer and
      integrated crossed screws. The stiffness of each construct was then compared with
      the intact specimen. Specimens with obvious deformity on radiographs or dual
      energy radiograph absorptiometry t score values <-1.2 were excluded. RESULTS: The
      addition of the integrated crossed metal screw system improved the stiffness of
      the construct by 53% over the intact (P = 0.02) and by 31% over the FRA alone in
      extension (P = 0.01), whereas it improved the stiffness by 40% over the intact (P
      = 0.03) and by 18% over the FRA alone in torsion (P = 0.21). The crossed screw
      system did not improve the stiffness compared with intact in either flexion or
      lateral bending modes. CONCLUSIONS: Although there is a trend toward improved
      stability of the FRA spacers in torsion with the addition of the metal screws,
      this is not statistically significant. The integrated crossed anterior metal
      screw system significantly improves the stability of the FRA spacers in extension
      when used for anterior lumbar interbody fusion.

PMID- 11979163
TI  - Artificial intervertebral disc replacement using bioactive three-dimensional
      fabric: design, development, and preliminary animal study.
AB  - STUDY DESIGN: A new artificial intervertebral disc was developed, and its
      intrinsic biomechanical properties, bioactivity, and the effectiveness as a total
      disc replacement were evaluated in vitro and in vivo. OBJECTIVES: To introduce a
      new artificial intervertebral disc and to evaluate the in vitro mechanical
      properties, fusion capacity to bone, and segmental biomechanics in the total
      intervertebral disc replacement using a sheep lumbar spine. SUMMARY OF BACKGROUND
      DATA: The loss of biologic fusion at the bone-implant interface and prosthetic
      failures have been reported in previous artificial discs. There have been no
      clinically applicable discs with detailed experimental testing of in vivo
      mechanics and interface fusion capacity. METHODS: The artificial intervertebral
      disc consists of a triaxial three-dimensional fabric (3-DF) woven with an ultra
      high molecular weight polyethylene fiber, and spray-coated bioactive ceramics on
      the disc surface. The arrangement of weave properties was designed to produce
      mechanical behavior nearly equivalent to the natural intervertebral disc. Total
      intervertebral disc replacement at L2-L3 and L4-L5 was performed using 3-DF disc
      with or without internal fixation in a sheep lumbar spine model. The segmental
      biomechanics and interface histology were evaluated after surgery at 4 and 6
      months. RESULTS: The tensile-compressive and torsional properties of prototype 3
      DF were nearly equivalent to those of human lumbar disc. The lumbar segments
      replaced with 3-DF disc alone showed a significant decrease of flexion-extension
      range of motion to 28% of control values as well as partial bony fusion at 6
      months. However, the use of temporary fixation provided a nearly physiologic
      mobility of the spinal segment after implant removal as well as excellent bone
      disc fusion at 6 months. CONCLUSION: An artificial intervertebral disc using a
      three-dimensional fabric demonstrated excellent in vitro and in vivo performance
      in both biomechanics and interface histology. There is a potential for future
      clinical application.

PMID- 11979165
TI  - Axial and tangential fixation strength of pedicle screws versus hooks in the
      thoracic spine in relation to bone mineral density.
AB  - STUDY DESIGN: In vitro biomechanical testing was performed to analyze the axial
      and tangential fixation strength of pedicle screws versus pedicle and laminar
      hooks in the human thoracic spine. Bone mineral density of each tested vertebra
      was determined. OBJECTIVE: To study the fixation strength of pedicle screws and
      hooks in the thoracic spine in relation to bone mineral density. SUMMARY OF
      BACKGROUND DATA: Biomechanical properties of pedicle screws have proven to be
      superior in the lumbar spine, but there is a paucity of data concerning the
      thoracic spine in particular with regard to bone mineral density. METHODS: In 72
      human thoracic vertebrae standard pedicle hooks between T4 and T8 and
      supralaminar hooks between T9 and T12 were tested against pedicle screws in pairs
      in one vertebra each. The bone mineral density of each vertebra was determined by
      means of quantitative computed tomography. Screws and hooks were loaded either
      axially strictly longitudinal to failure or in a coronal plane strictly
      perpendicular to the longitudinal axis nondestructively. A total of 78 pullout
      tests and 66 tangential loadings were performed. RESULTS: The correlation of bone
      mineral density and fixation strength was significant for pullout strength of
      pedicle screws (P < 0.001) and pedicle hooks (P < 0.001). The average pullout
      strength of the pedicle screws was significantly higher than that of pedicle
      hooks (P = 0.003) and supralaminar hooks (P = 0.02). The difference was not
      significant if bone mineral density was <100 mg hydroxylapatite/mL. The average
      tangential elastic and permanent displacement of pedicle screws was significantly
      lower than that of pedicle (P < 0.001) and laminar hooks (P = 0.002). CONCLUSION:
      Pedicle screws may be beneficial for instrumentation of the thoracic spine
      because they are significantly more resistant to axial and tangential loadings
      than pedicle and laminar hooks on the condition that bone mineral density is >100
      mg/mL hydroxylapatite.

PMID- 11979166
TI  - Long-term results of operative treatment for cervical spondylotic myelopathy in
      patients with athetoid cerebral palsy: an over 10-year follow-up study.
AB  - STUDY DESIGN: A retrospective radiographic and medical record analysis of
      patients followed for more than 10 years after operative treatment for cervical
      spondylotic myelopathy complicating athetoid cerebral palsy. OBJECTIVE: To
      describe the incidence of late neurologic deterioration and spinal deformity
      after operative treatment for cervical spondylotic myelopathy in athetoid
      cerebral palsy. SUMMARY OF BACKGROUND DATA: The possibility of recurrence of
      symptoms after operative treatment for cervical spondylotic myelopathy seems
      greater in patients with athetoid cerebral palsy because of their involuntary
      neck movements. Although there are several reports of surgical results, long-term
      follow-up studies are very rare. METHODS: Ten patients with athetoid cerebral
      palsy were evaluated over an average of 15 years after anterior decompression
      (corpectomy) and fusion (three patients), laminectomy (one patient), and
      laminoplasty (six patients, four with accompanying posterior fusion). They
      averaged 45 years of age at surgery. Surgical results were assessed using
      Kurokawa's method. Late neurologic deterioration was based on decrement in the
      JOA score, and the evolution of kyphosis or instability of the cervical spine was
      observed radiographically. RESULTS: Surgical results at the most improved period
      were good or excellent in all 10 patients. Eight showed late neurologic
      deterioration, however, and six of them deteriorated from 8 to 13 years after
      surgery, largely because of progressive deformity. CONCLUSIONS: Long-term follow
      up evaluation is essential in any type of operation, particularly with patients
      with athetoid cerebral palsy who often undergo this operation in their 30s or
      40s.

PMID- 11979168
TI  - Airway complications associated with surgery on the anterior cervical spine.
AB  - STUDY DESIGN: Retrospective chart review of 311 anterior cervical procedures.
      OBJECTIVES: To assess the incidence and variables that predispose to an airway
      complication in a large series of anterior cervical surgical procedures. SUMMARY
      OF BACKGROUND DATA: A rare but potentially lethal complication after anterior
      cervical spine surgery is respiratory compromise and airway obstruction. Some
      risk factors are thought to include two-level corpectomy in myelopathic patients
      with a history of heavy smoking and asthma. No previous study in the literature
      has been directed at examining the factors specifically related to airway
      complications after anterior cervical spine surgery. METHODS: Each chart was
      examined for patient characteristics and pathology, anesthetic parameters and
      problems, operative procedure, and postoperative course and management.
      Statistical analysis was performed. RESULTS: Nineteen patients (6.1%) had an
      airway complication and six (1.9%) required reintubation. One patient died.
      Symptoms developed on average 36 hours postoperatively. All complications except
      for two were attributable to pharyngeal edema. Variables that were found to be
      statistically associated with an airway complication (P < 0.05) were exposing
      more than three vertebral bodies, a blood loss >300 mL, exposures involving C2,
      C3, or C4, and an operative time >5 hours. A history of myelopathy, spinal cord
      injury, pulmonary problems, smoking, anesthetic risk factors, and the absence of
      a drain did not correlate with an airway complication. CONCLUSIONS: Patients with
      prolonged procedures (i.e., >5 hours) exposing more than three vertebral levels
      that include C2, C3, or C4 with more than 300-mL blood loss should be watched
      carefully for respiratory insufficiency.

PMID- 11979169
TI  - Intraoperative measurement of lumbar spine motion segment stiffness.
AB  - STUDY DESIGN: Prospective trial. OBJECTIVES: To test an intraoperative diagnostic
      tool to determine if it provided the surgeon with a safe, reproducible, accurate,
      quantitative measure of lumbar spine motion segment stability. SUMMARY OF
      BACKGROUND DATA: Several devices have been developed to measure motion segment
      stiffness, however, few have been tested intraoperatively on humans, and none, to
      the best of the authors' knowledge have been tested as extensively as the device
      described in this study. Objective criteria, such as those provided by an
      intraoperative gauge, can be helpful in determining when and what type of fusion
      of a degenerated spinal motion segment unit should be performed following
      decompressive surgery. METHODS: The spinal stiffness gauge, placed between
      spinous processes of adjacent vertebrae, applies a controlled, constant loading
      rate along the spine's longitudinal axis, producing a load-displacement curve
      from which stiffness, range of motion, and hysteresis can be computed.
      Measurements from this tool were then used to investigate differences in
      stiffness of the motion segment before and after decompressive surgery, between
      spine levels, and between male and female subjects. RESULTS: The spinal stiffness
      gauge stiffness measurements correlated with the surgeon's subjective stiffness
      measurements on the same motion segments. The stiffness measurements had
      excellent repeatability. Stiffness was dependent on the spine level, gender, and
      degree of disc degeneration. CONCLUSIONS: This study demonstrated the efficacy of
      the spinal stiffness gauge for providing an objective, quantitative,
      intraoperative stiffness (stability) measurement of the lumbar spine motion
      segment.

PMID- 11979170
TI  - The clinical usefulness of intraoperative spinal stiffness measurements.
AB  - STUDY DESIGN: Determination of clinical results at least 2 years after lumbar
      spine surgery during which spinal stiffness measurements were made. OBJECTIVES:
      To determine whether spine stiffness is predictive of clinical results after
      lumbar spine surgery for spinal stenosis, disc herniation, or degenerative
      spondylolisthesis. SUMMARY OF BACKGROUND DATA: The implied clinical wisdom is
      that instability of the spine portends a poor prognosis for relief of back pain
      after surgery in the absence of a fusion. The possibility that an objective
      measure of lumbar spinal motion segment unit stiffness could aid the surgeon in
      predicting satisfaction with treatment was considered. METHODS: A total of 298
      patients were measured intraoperatively with the spinal stiffness gauge to
      determine motion segment stiffness. Intraoperative spinal stiffness was analyzed
      to determine the influence of this measurement on clinical results. RESULTS:
      Statistical analysis revealed that stiffness measurements did not correlate with
      clinical results of surgery. Patients with loose motion segment units before
      decompression did not demonstrate a significantly different level of satisfaction
      with surgical results a minimum of 2 years after surgery, whether they were fused
      or not fused. Based on stiffness measurements, a diagnosis of herniated nucleus
      pulposus or degenerative spondylolisthesis was indicative of a more unstable
      spine than a diagnosis of spinal stenosis. CONCLUSIONS: Intraoperative spinal
      stiffness measurements did not predict clinical results after lumbar spine
      surgery.

PMID- 11979171
TI  - Spine infections: variations in incidence during the academic year.
AB  - STUDY DESIGN: A prospective analysis of variations in monthly spinal infection
      rates at a spinal cord injury center with resident and fellow involvement in
      surgical care. OBJECTIVE: To analyze the association between resident and fellow
      participation in spinal surgery and the incidence of perioperative wound
      infection over the academic year. SUMMARY OF BACKGROUND DATA: It has been
      hypothesized that resident and fellow participation in surgical procedures may
      account for increased wound complications. Previous spinal infection studies have
      not addressed variations in the incidence of perioperative wound infections over
      the academic year. METHODS: All cases of postoperative spinal infections at a
      spinal cord injury center from January 1994 through December 1997 were analyzed
      to determine whether monthly variations reflect the changes in surgical house
      officer experience through the academic year. RESULTS: A statistically
      significant (P < 0.027) increase in the incidence of spinal infection was
      demonstrated for the month of January. No other significant variations in the
      monthly incidence of spinal infection existed. No significant differences were
      found when the data were analyzed: year-to-year (P < 0.727), season-to-season (P
      < 0.204), 4-month resident rotation (P < 0.061), and 6-month fellow rotation (P <
      0.075). CONCLUSION: A significantly higher incidence of spinal infection (10.5%)
      was observed for the month of January. Because January does not represent the
      start of a new resident or fellow rotation, there appears to be no association
      between the incidence of perioperative spinal wound infections and the level of
      experience of the surgical house officers in a regional spinal cord injury
      center.

PMID- 11979172
TI  - Intradiscal electrothermal treatment for chronic discogenic low back pain:
      prospective outcome study with a minimum 2-year follow-up.
AB  - STUDY DESIGN: Prospective longitudinal study with a minimum 2-year follow-up.
      OBJECTIVE: To assess the long-term outcome of a group of patients with chronic
      discogenic low back pain who had failed to improve with comprehensive
      nonoperative care and who were subsequently treated with intradiscal
      electrothermal therapy (IDET). SUMMARY OF BACKGROUND DATA: Previous reports of
      patient outcomes at 1 year after IDET have demonstrated statistically significant
      improvement. METHODS: The study group comprised 58 patients with chronic symptoms
      of more than 6 months who failed to improve with nonoperative care and
      subsequently underwent IDET. VAS pain scores, SF-36 scores, and sitting tolerance
      times were collected pretreatment and at 6, 12, and 24 months. RESULTS: Mean
      duration of pre-IDET symptoms was 60.7 months. The minimum follow-up at data
      collection was 24 months. The study group (n = 58) demonstrated a significant
      improvement in pain as demonstrated by statistically significant improvement in
      VAS scores and bodily pain SF-36 scores. The IDET-treated group demonstrated a
      significant improvement in physical function as noted by statistically
      significant improvement in sitting tolerance times and physical function SF-36
      scores. Bodily pain and physical function scores demonstrated significant
      improvement between the 1- and 2-year observation points. Additionally, quality
      of life improvement was demonstrated by a statistically significant improvement
      in all the SF-36 subscales. CONCLUSIONS: A cohort of patients with chronic
      discogenic low back pain who had failed to improve with comprehensive
      nonoperative care demonstrated a statistically significant improvement in pain,
      physical function, and quality of life at 2 years after IDET.

PMID- 11979174
TI  - Impaired lumbar movement perception in association with postural stability and
      motor- and somatosensory-evoked potentials in lumbar spinal stenosis.
AB  - STUDY DESIGN: A descriptive study of the associations between different
      neurophysiologic findings in patients with lumbar spinal stenosis. OBJECTIVES: To
      evaluate the ability to sense a change in lumbar position and the associations
      between lumbar movement perception, postural stability, and motor-evoked
      potentials and somatosensory-evoked potentials. SUMMARY OF BACKGROUND DATA:
      Patients with low back pain have impaired postural control and impaired lumbar
      proprioception. Altered motor-evoked potentials and somatosensory-evoked
      potentials have been often observed in lumbar spinal stenosis. METHODS: The study
      included 26 patients with clinically and radiologically diagnosed lumbar spinal
      stenosis. Their ability to sense lumbar rotation was assessed in a previously
      validated motorized trunk rotation unit in the seated position. The abilities to
      indicate the movement direction and the movement magnitude were used as indexes
      of the ability to sense the lumbar rotatory movement. The postural stability was
      measured with a vertical force platform. The motor-evoked potentials were
      elicited by transcranial and lumbar stimulation and recorded from anterior
      tibialis muscles. The somatosensory-evoked potentials were elicited by
      transcutaneous electrical stimulation of the tibial nerve at the ankle. RESULTS:
      Twenty patients (76.9%; P = 0.006) reported the wrong movement direction.
      Furthermore, the patients consistently localized the movement sensation in their
      shoulders instead of the lumbar region. The altered motor-evoked potentials and
      somatosensory-evoked potentials were observed in 11 and 16 patients,
      respectively. Abnormal motor-evoked potentials had inconsistent associations with
      impaired movement perception and postural stability and abnormal somatosensory
      evoked potentials had no associations with other findings. CONCLUSIONS: Many
      patients with lumbar spinal stenosis have difficulties in sensing the lumbar
      rotational movement, which may indicate impaired proprioceptive abilities.
      Abnormal motor-evoked potentials and somatosensory-evoked potentials are also
      frequent in lumbar spinal stenosis but do not necessarily occur in the same
      patients as the abnormal ability to sense trunk movement. These new findings add
      to our understanding of the pathophysiology of lumbar spinal stenosis.

PMID- 11979175
TI  - Low back pain recollection versus concurrent accounts: outcomes analysis.
AB  - STUDY DESIGN: Patients with low back pain were asked to recall the pain and
      impaired functioning that they reported 5-10 years previously as part of the
      National Low Back Pain prospective follow-up study. In 1998, patients completed
      an additional follow-up. OBJECTIVES: To compare outcomes using patient-recalled
      data and prospectively collected data from patients with low back pain and to
      identify simple, symptom-specific questions that yield reliable responses over an
      extended period of time. SUMMARY OF BACKGROUND DATA: Outcome assessment based on
      patient recall may be influenced by a patient's age, gender, reporting tendency,
      and current health status. The impact of data collected retrospectively on
      outcome analyses in spinal patients has not been addressed. METHODS: Patients
      enrolled in the National Low Back Pain study from 1986 to 1991 completed a self
      administered questionnaire at their initial visit. A sample was interviewed by
      telephone in 1996 and asked to recall pain characteristics and impaired
      functioning reported at initial examination. A 10-year follow-up (1998) on
      current health status was conducted by mail. The 1998 follow-up response was
      separately compared with recalled and initial responses, such that two patient
      outcome status values were calculated for each question. Agreement was evaluated
      using Cohen's kappa. RESULTS: The follow-up evaluation was completed by 144
      patients, with a mean interval of 9.4 years. The overall simple kappa was 0.37,
      indicating "fair" agreement between outcomes based on initial and recalled
      accounts of pain. Questions on location of pain had kappa values of 0.12-0.58,
      radicular symptoms 0.28-0.48, and severity of pain 0.11-0.30. CONCLUSIONS: "Fair"
      to "moderate" agreement was found between outcomes determined by recalled versus
      initial reports. Accuracy was greatest for queries on frequency, location of
      pain, and activities affecting pain. Discrepancies were noted for queries on
      severity of pain, with error bias toward less pain when using the recalled data.
      Careful selection of questions may yield more accurate outcome measures.

PMID- 11979177
TI  - Helmet and shoulder pad removal in suspected cervical spine injury: human control
      model.
AB  - STUDY DESIGN: Digital fluoroscopy was used to evaluate the motion in normal men
      during helmet and shoulder pad removal. OBJECTIVES: To observe the amount of
      motion that occurs during the removal of helmet and shoulder pads in an uninjured
      spine. SUMMARY OF BACKGROUND DATA: Removal of shoulder pads and helmet from a
      football player with suspected cervical spine injury can be particularly
      hazardous. Previous studies have been performed in cadavers with known created
      injuries. No control study in uninjured players has been done to show if there is
      similar motion with removal of football equipment. METHODS: Four people removed
      the helmet and shoulder pads with a technique consistent with that described by
      the National Athletic Trainers' Association (NATA). Before positioning, with the
      helmet and shoulder pads on the subject and the subject lying flat on the table,
      one static lateral image was obtained as a baseline. With the neck stabilized and
      everyone in position, the torso, head, and neck were elevated approximately 30-40
      degrees off the table bending at the waist. After elevation, continuous
      fluoroscopy was turned on as the helmet and shoulder pads were removed. Once the
      equipment was removed, the subject was carefully placed back down on the table
      and a final static lateral image was obtained. All images were saved digitally.
      Measurements were made for change in angulation, translation, distraction, and
      space available for the cord. RESULTS: The results for change in disc height,
      translation, and space available for the cord showed no significant change. The
      results for change in angulation also did not show any significant motion in
      either flexion or extension from baseline or between each step in the protocol.
      CONCLUSIONS: In the conscious player with no cervical injury the protocol used by
      the NATA is effective in limiting cervical motion.

PMID- 11979179
TI  - Role of "Bovie" in spinal surgery: historical and analytical perspective.
AB  - INTRODUCTION: Several surgeons use electrocautery (Bovie) discreetly or avoid it
      completely with the fear of increasing the chances of postoperative infection and
      delaying wound healing. However, the experience of many other surgeons is
      different. The current authors have used Bovie extensively to perform a broad
      array of spinal surgeries. Their rate of infection in spinal surgery can be
      positively compared with the existing literature where Bovie has been used to
      variable extent. The purpose of this study is to project the authors' concept
      that the use of Bovie dissection in spinal surgery does not increase the chances
      of postoperative wound infection. METHODS: A MEDLINE search was carried out to
      determine various aspects of Bovie, including historical perspectives, circuit
      design, tissue response, effect on wound healing, determination of wound
      infection, and role of surgical smoke. The search also included the rate of
      infection after various spinal surgeries in the existing literature (up to 15%).
      MATERIALS: In the span of 5 years (1996-2000), 322 spinal surgeries of various
      kinds were performed at Children's Hospital Medical Center (Cincinnati, Ohio).
      Most of them were performed by the senior author (A.H.C.). There were 102 cases
      of idiopathic scoliosis (two infected [2%]), 53 cases of neuromuscular scoliosis
      (two infected [4%]), and 167 cases of other spinal surgeries (three infected
      [1.8%]). Of these seven patients who developed wound infection in the
      postoperative period, one had superficial and six had deep infection. The overall
      rate of wound infection was 2%. Development of infection elsewhere in the body
      after surgery, such as respiratory, pleural, or urinary tract infections, has not
      been included in this analysis. RESULTS: Despite the fact that the authors have
      extensively used Bovie in spinal surgery, their rate of postoperative wound
      infection is comparable with the rate of infection cited in the available
      literature where Bovie was used to a variable extent. It strongly suggests that
      the use of Bovie does not increase the chances of postoperative wound infection.
      DISCUSSION: The role of Bovie for musculoskeletal surgery in general and spinal
      surgery in particular is not well defined. A review of the available literature
      indicates that Bovie delays the wound healing and increases the chances of
      infection. The authors' experience with the Bovie and this indirect method of
      analysis suggest that Bovie does not increase the chances of infection. A
      detailed search of the literature has been presented along with historical and
      analytical perspectives. More clinical and experimental studies are needed to
      further substantiate this claim. If future publications describe the exact
      surgical technique, extent of the use of Bovie, infection containment
      (antibiotic) method used before, during, and after surgery, length of the
      operative exposure, duration of the surgery, and rate of infection, then a meta
      analysis of the published clinical material from different centers could be
      performed, which would provide more comprehensive information.

PMID- 11979180
TI  - Nontraumatic pancreatitis in spinal cord injury.
AB  - STUDY DESIGN: A retrospective analysis of 10 patients with pancreatitis after
      traumatic spinal cord injury. OBJECTIVES: To determine the conditions leading to
      nontraumatic pancreatitis in spinal cord injury. SUMMARY OF BACKGROUND DATA:
      Little is known in the literature about pancreatitis after spinal cord injury. A
      few authors suggest a multifactorial pathogenesis. METHODS: Over a 4-year period
      the case reports of 338 patients with traumatically caused SCI were reviewed
      concerning p-amylase and/or lipase elevations. Acute pancreatitis was defined as
      an elevation of p-amylase and/or lipase of more than three times the upper normal
      limit. RESULTS: Ten of 338 patients had p-amylase and/or lipase elevations three
      times higher than the upper normal limit. All 10 were male with a mean age of
      40.4 years. The average onset time of acute pancreatitis was 16 +/- 5.5 days
      after trauma. The usual etiologic factors of acute pancreatitis such as
      obstructive, toxic, or traumatic events were excluded. CONCLUSION: The clinical
      recognition of acute pancreatitis in paraplegic and quadriplegic patients is
      hampered by diminished or lost visceral sensitivity and therefore is based on
      laboratory investigations. The current authors therefore hypothesize that acute
      pancreatitis in the setting of high-level spinal cord injury may result from a
      combination of locally mediated sphincter of Oddi dysfunction and vagal dominant
      innervation of the pancreatic gland in autonomic failure.

PMID- 11979181
TI  - Idiopathic spinal cord herniation: report of eight cases and review of the
      literature.
AB  - STUDY DESIGN: A case series of eight patients with idiopathic spinal cord
      herniation and a review of the literature. OBJECTIVE: To report on this rare
      entity, provide insight on its natural history, and propose an optimal management
      strategy. SUMMARY OF BACKGROUND DATA: Idiopathic spinal cord herniation is a rare
      disease with 50 cases reported before the current study. METHODS: Eight cases
      (follow-up 1 month to 8 years) are reported using available information from
      patient charts, interviews, and assessments. All imaging studies are reviewed.
      The review of the literature was performed using PUBMED. RESULTS: Four patients,
      followed without surgical intervention, have not progressed. Of the three
      patients who underwent surgical repair by one of the authors, two improved and
      one was unchanged. A fourth patient, who was initially treated by another surgeon
      who failed to identify the dural defect and herniation, had a poor outcome.
      CONCLUSION: The pathophysiology of the dural defect is still uncertain. The
      typical presentation is Brown-Sequard syndrome. Microsurgical repair in cases
      with progression of neurologic deficits is usually successful in achieving
      recovery of function or arrest of progression.

PMID- 11979182
TI  - The ivory vertebra: an approach to investigation and management based on two case
      studies.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To report and discuss the natural
      evolution of fortuitously found solitary radiodense or "ivory" vertebrae in two
      asymptomatic patients; to review the existing literature concerning ivory
      vertebrae; and to provide a practical guide for the diagnostic and management
      approach to the fortuitous finding of ivory vertebrae in asymptomatic patients.
      SUMMARY OF BACKGROUND DATA: The asymptomatic and apparently idiopathic ivory
      vertebra is often a very problematic clinical situation. Previous studies have
      hypothesized that although several etiologies have been known to be responsible
      for producing ivory vertebrae, the most likely etiology, particularly for so
      called "idiopathic" ivory vertebrae, is early and asymptomatic Paget's disease of
      bone. METHODS: Two patients, each with an incidentally discovered ivory vertebra,
      were followed clinically over a period of 13 and 10 years, respectively. During
      this time the patients underwent a multitude of investigations in an attempt to
      identify the etiology of the ivory vertebra. After having eliminated ominous
      etiologies, the authors opted for a conservative approach to management
      (observation) so as to have a long-term follow-up of the patients and also
      attempt to determine the natural history of idiopathic solitary ivory vertebrae.
      RESULTS: Despite the extensive workups, no etiology was ever found for either
      patient because the tests showed normal results for extended periods of time.
      Whereas in one patient Paget's disease of bone was suspected, no definitive
      confirmation for the presence of Paget's disease could be obtained, even on bone
      biopsy. Both patients remained entirely asymptomatic with respect to the ivory
      vertebra over the entire follow-up period. CONCLUSION: Based on the observations
      from the present study as well as a review of the literature on the subject, a
      decision-making algorithm is put forth for the investigative approach as well as
      for the subsequent follow-up and management of patients with idiopathic and
      asymptomatic ivory vertebrae whereby, after baseline screening tests eliminate
      ominous pathology, observation and periodic clinical reassessment are advised
      until symptoms develop or until there are radiographic changes in the appearance
      of the ivory vertebra.

PMID- 11979183
TI  - "Spinolith": case report of a loose body in the spinal canal.
AB  - STUDY DESIGN: Case report. A hitherto unreported finding of a bony loose body
      found lying in the spinal canal causing spinal canal stenosis is presented.
      SUMMARY OF CLINICAL DETAILS: A 68-year-old, fit man presented with a history of
      progressive neurologic claudication and neurologic deficit in both his lower
      limbs. Clinical examination revealed excellent range of movements in his lumbar
      spine and bilaterally normal straight leg raising. He had no significant pain in
      his back. Neurologic examination showed affection of L5 and S1 dermatomes and
      myotomes bilaterally. Magnetic resonance imaging scan showed severe localized
      lumbar spinal stenosis at L4-L5. In the absence of any obvious pathology on the
      scan, it was presumed that the stenosis was the result of infolding of the
      redundant ligamentum flavum. His walking distance and neurologic deficit
      continued to deteriorate, although sphincters were not involved. He underwent a
      posterior spinal decompression of L4-L5. On performing the laminectomy an ovoid
      and well-defined pearly white loose body was discovered lying loose in the spinal
      canal causing stenosis. Histologically, the loose body consisted of trabecular
      bone with areas of cartilage. The patient made a speedy recovery after surgery
      and was back to his previous level of activity within a month. DISCUSSION:
      Several different types of foreign body have been identified in the spinal canal.
      However, this case of an autologous loose body in the spinal canal causing
      symptomatic canal stenosis is unique. Because the authors could not identify the
      source of this loose body, they have termed it "spinolith."

PMID- 11979185
TI  - Teamwork and initiatives in tissue viability nursing.

PMID- 11979186
TI  - Support the new Tissue Viability Nurses' Association.

PMID- 11979184
TI  - Spinal brucellosis: case report in the United States.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To increase awareness of spinal brucellosis
      and discuss demographics, diagnosis, and treatment. SUMMARY OF BACKGROUND DATA:
      Brucellosis is a rare cause of spinal infections in the United States, although
      there have been regional increases in its prevalence. METHODS: Retrospective
      review of a patient with spinal brucellosis. She underwent a protracted course of
      treatment, with a long delay in diagnosis. History ultimately revealed regular
      consumption of unpasteurized goat cheese. Appropriate testing subsequently led to
      the diagnosis. RESULTS: After multiple surgeries and medications, the condition
      responded well to definitive antibiotic therapy. CONCLUSION: Brucellosis is rare
      in the United States and thus often overlooked in the differential diagnosis of
      back pain. The changing risk pattern for this disease requires a high index of
      suspicion, which can result in early diagnosis and predictably favorable results
      to treatment.

PMID- 11979187
TI  - Announcement of launch of the Tissue Viability Nurses' Association.
AB  - The Tissue Viability Nurses' Association (TVNA) has been formed recently to
      represent the professional and political interests of tissue viability nurses.
      This article discusses the evolution of the new Association and the developments
      to date. The TVNA's constitution is published, and potential and future
      developments of the Association are discussed. It is imperative that tissue
      viability nurses have a voice. The TVNA intends to be a recognized, democratic,
      representative and active body with whom governmental and other organizations can
      collaborate and consult. This will enable tissue viability nurses to influence
      policy and practice.

PMID- 11979188
TI  - Injecting drug use: implications for skin and wound management.
AB  - This article, the first of two parts, introduces the difficulties facing nurses
      working with injecting drug users with skin problems. Drug abuse is increasing
      globally, and has huge implications for healthcare practitioners. Increasing
      numbers of tissue viability nurses are also encountering drug injection-induced
      wounds in their practice, but there is a lack of evidence for management of
      chronic skin problems in this patient group. Together with rising numbers of
      injecting drug users, there are increased health implications such as
      bacteraemia, septicaemia, amputation and skin breakdown. Abscesses and chronic
      wounds as well as prolonged leg ulceration are common. Drug users may demonstrate
      chaotic lifestyles, which may inhibit access to usual healthcare provision.
      Issues relating to healing of these wounds are explored. The second part, which
      will appear in the next Tissue Viability Supplement, will describe the
      development of a specialist wound care clinic for homeless drug users.

PMID- 11979189
TI  - Topical negative pressure for pressure ulcer management.
AB  - The use of negative pressure therapy has been reported previously in a variety of
      care settings, but not in spinal cord-injured (SCI) patients. These individuals
      are at greatly increased risk of pressure ulcer development because of many
      factors associated with their neurological deficit and the incidence of pressure
      ulcers is high among them. This small case series employed objective measures to
      evaluate the effectiveness of negative pressure therapy when used to prepare
      pressure ulcers for surgical closure. The treated wounds demonstrated increased
      granulation tissue development and reduced wound colonization, and the reduced
      frequency of dressing changes compared with other treatment options may reduce
      the nursing workload. These case studies highlight the benefits of negative
      pressure therapy to SCI patients and emphasise the need for further work to
      compare the technique with other treatment options and determine the optimal
      application parameters of negative therapy in this patient group.

PMID- 11979190
TI  - Telemedicine: an innovative way of managing patients with leg ulcers.
AB  - The optimal management of patients with leg ulcers requires a multidisciplinary
      approach, with contributions from both community and hospital specialists to
      identify, investigate and treat the underlying causes, provide patient education,
      assess healing and dress the wounds, monitor outcome and prevent recurrence.
      However, current practice is impaired by the limited communication between
      community and hospital specialists. There are inconsistencies in methods of
      transferring and updating patient records between the hospital and the community,
      and this can lead to confusion over the diagnosis and appropriate management.
      Telemedicine, the electronic exchange of medical information at a distance, would
      appear to offer a way to establish an efficient and effective communication link
      between hospital and community specialists involved in the care of patients with
      leg ulcers. The authors of this article believe that modern information
      technology and the existing NHSnet information infrastructure could be employed
      to create such a link via electronic patient records.

PMID- 11979191
TI  - Metronidazole gel in managing malodorous fungating wounds.
AB  - Historically, the incidence of fungating wounds is not well documented. This
      article looks at the limited up-to-date information on the impact and incidence
      of fungating wounds in the UK. As fungating wounds generally signal palliative
      care and rarely heal, the ability to manage their unpleasant symptoms is
      increasingly important. One of the most distressing symptoms identified by
      patients is malodour; therefore, this article will review the limited research
      available on the use of metronidazole preparations to manage malodorous wounds.

PMID- 11979192
TI  - Improtec R Barrier: a mattress cover which does not break down.
AB  - Mattress cover material breakdown in the clinical setting has been a recognized
      problem for over 10 years. Shortly following disruption to the surface integrity,
      mattresses become contaminated with body fluids, which leads to bottoming-out of
      the foam, putting patients at increased risk of infection and pressure ulcer
      formation. Collaboration between manufacturers and clinicians has produced a
      product that should stand up to the rigours of the healthcare market, providing
      safety for patients and value for money as a result of extended mattress life.

PMID- 11979193
TI  - Our lives, our bodies: thorny issues of consent.

PMID- 11979194
TI  - Promoting excellence in primary care 2002: conference report.

PMID- 11979195
TI  - Overactive bladder: a challenge for primary care.
AB  - The important role that members of the primary health care team play in the
      treatment of urinary incontinence is widely recognized (Department of Health
      (DH), 2000). Incontinence within the general population is increasing and is
      known to be an embarrassing and distressing condition. It remains a taboo subject
      that is difficult to talk about even with a trusted health professional. As a
      result patients suffer from social isolation and a reduction in self-esteem.
      Members of the primary health care team are well placed to raise awareness about
      the treatment options. Nurses' involvement in the treatment and management of
      incontinence is set to increase (DH, 2001). This article aims to review the types
      of incontinence and the treatment options available to members of the primary
      health care team. The 'National Service Framework for Older People' (DH, 2001)
      has set us the task of establishing integrated continence services by 2004. This
      provides nurses with the opportunity to work in partnership to target this
      distressing and embarrassing condition.

PMID- 11979196
TI  - Smoking cessation: a role for every practitioner.
AB  - Despite the long-term efforts of governments and health professionals, smoking is
      still the single most important public health problem in the UK today. The
      addictiveness of nicotine means that very few unsupported attempts to quit are
      successful. This article provides an overview of the public health implications
      of smoking in the UK, the benefits of stopping smoking, and examines what
      community nurses can do to help and support people who want to quit.

PMID- 11979197
TI  - Mind the gap: voluntary sector pregnancy advice service.
AB  - This article describes a voluntary pregnancy advisory service in a deprived inner
      city area and summarizes some descriptive statistics kept relating to one year
      (2000). The evidence suggests that this service was acceptable to women in the
      local area and frequently used by them. Possible reasons why the service may be
      acceptable are discussed, followed by an attempt to explore how such voluntary
      sector organizations could work in partnership with the health services, both by
      supplementing them, and also by providing an interface between the local
      community and the health services to encourage appropriate and effective use of
      the statutory services by more marginalized members of the communities which they
      serve.

PMID- 11979199
TI  - Pharmacological management of smoking cessation.
AB  - There is evidence that pharmacological management of smoking cessation, together
      with advice and support, is very cost-effective and increases success rates of
      quit attempts. Community nurses are in a good position to intervene with smokers.
      All nicotine replacement therapy products are now on the Nurse Prescribers'
      Formulary. This article covers the scientific evidence, the guidelines on smoking
      cessation and the role of the health professional. Treatment options are
      described and useful contacts for further information are provided.

PMID- 11979198
TI  - Disseminating weaning messages: an intervention trial.
AB  - This article reports a non-randomized intervention study conducted in two market
      towns to find out whether participant-centred health education discussions
      improve parents' knowledge and actions concerning infant feeding. Following an
      initial quiz, parents of 8-week-old infants attended a discussion on weaning
      (intervention) or home safety (control). They were then asked to complete a
      questionnaire about their knowledge and actions concerning weaning when their
      infants were 7-9 months old. A total of 61 parents took part in the intervention
      and 49 in the control. In the post-intervention questionnaire, the intervention
      group reported using more home-cooked foods and less commercially-prepared foods
      and knew the optimum time to register their infants with the dentist. These
      results suggest that participant-centred discussions are an effective way of
      disseminating public health messages concerning infant feeding.

PMID- 11979200
TI  - Does pacifier use cause ear infections in young children?
AB  - The aim of this review was to identify whether, in children under 2 years of age,
      pacifier (dummy) use results in an increased risk of ear infection (acute otitis
      media). The Cochrane Library, Medline, CINAHL and Embase databases were searched
      for cohort studies and randomised controlled trials that compared infants who
      used pacifiers with those who didn't or examined the effect of reducing pacifier
      use in a group of infants. One cluster randomised trial and two cohort studies
      met the review criteria and were available to be included in the body of the
      review. These studies show a clear increase in risk of ear infection to be
      associated with use of a pacifier that may well be causal. The risk of ear
      infections is up to three times higher in those who use a pacifier and there does
      appear to be a 'dose response' with continual users more at risk than occasional
      users. However, this relationship may be confounded by socio-demographic factors.
      Rather than advising a parent not to use a pacifier for fear of causing otitis
      media, advice in relation to this issue might best be restricted to pacifier
      users suffering from the problem in order to reduce the chances of recurrence.

PMID- 11979201
TI  - Treating peristomal skin problems in the community.
AB  - Adaptation to life with a stoma depends to a large extent on the health of the
      peristomal skin. This area of skin can become damaged in various ways, and the
      resulting discomfort or pain can make the use of a stoma appliance difficult.
      Problems such as these can be one of the major factors facing a community nurse
      in her/his care of the stoma patient. If the community nurse is able to recognize
      and correct these problems, this will enable the patient to carry on with a
      normal and productive life. Failure to correct stoma-related problems can have
      significant negative effects on patients' psychosocial well-being. This article
      discusses the causes and management of the commonest stoma-related skin problems.

PMID- 11979202
TI  - The shape of primary care in the future.

PMID- 11979203
TI  - Patients like nursing aspects of the nurse practitioner role.

PMID- 11979204
TI  - The district nursing workforce: so where do we go from here?

PMID- 11979205
TI  - Nurse in charge who lacked knowledge of medical condition.

PMID- 11979206
TI  - Lymphoedema 4: research priorities in lymphoedema care.
AB  - This article, the last in the series on lymphoedema, presents a survey of
      priorities in lymphoedema research conducted among lymphoedema treatment
      practitioners in the UK. Using a two-stage survey method, members of the British
      Lymphology Society were asked to identify areas lacking in a good evidence base
      which were crucial for informing clinical decision-making and service
      developments. Nine priority research questions were identified by the
      practitioners, with general agreement among respondents of the ranking order. The
      highest-ranking questions were: (1) What are the risk factors associated with
      lymphoedema? (2) How do we best treat skin infection/inflammation? (3) How
      effective is manual lymphatic drainage compared to other treatments?

PMID- 11979207
TI  - Health and safety regulations in relation to manual handling.

PMID- 11979208
TI  - Good practice in continence care: development of nurse-led service.
AB  - The implementation of evidence-based interventions in clinical practice is often
      alluded to in the literature; however, the development of these interventions is
      rarely documented. Within continence care, there is a larger body of relevant
      literature on which primary clinical interventions can be based. The
      Leicestershire Medical Research Council (MRC) Incontinence Study is a series of
      inter-related studies exploring the epidemiology of urinary symptoms, including
      incontinence, and evaluating service provision and treatment options for these
      symptoms. This article describes one aspect of the Leicestershire study, namely
      the development of evidence-based intervention protocols for use in a new nurse
      led continence service. This service is currently being evaluated in a randomised
      controlled trial.

PMID- 11979209
TI  - Caffeine reduction education to improve urinary symptoms.
AB  - Caffeine reduction is an internationally accepted treatment strategy for patients
      with urinary symptoms. However, there is little trial evidence in support of a
      caffeine/urinary symptom effect. A prospective randomized trial was conducted
      among 95 consecutive adult patients with urinary symptoms presenting to two nurse
      continence advisers. Frequency, urgency and leakage outcomes were tested 1 month
      postenrolment. Trial findings indicate that caffeine intake was reduced
      (P<0.0001) in the experimental group and that urgency (P=0.002) and frequency
      (P=0.037) outcomes were significantly improved. Caffeine practices and habits
      were surveyed and self-reports of caffeine effects indicate that urinary symptoms
      figured prominently as a reported effects but less so as a driver of caffeine
      reduction.

PMID- 11979210
TI  - Emotional and psychological preoperative preparation in adults.
AB  - Emotional and psychological surgical preparation plays an important role in many
      areas of nursing. However, it varies greatly in terms of its perception and
      delivery. The aim of this article is to familiarize the reader with the concept
      of emotional and psychological preparation for surgery and to explain how this
      may be achieved in nursing practice. It highlights that gender, age, and previous
      experiences are predisposing factors to preoperative anxiety, as is fear of the
      unknown and fear of harm. It is recommended that information should be given
      verbally with written supplements and that the patient should be encouraged to
      ask questions. Diversion therapy such as music, humour and guided imagery have
      been shown to be effective in reducing patients' preoperative anxiety.